(Medicalstudyzone - Com) Histology An Illustrated Colour Text-Churchill Livingstone

Histology
AN ILLUSTRATED COLOUR TEXT

For Elsevier
Commissioning Editor: Timothy Horne

Development Editor: Helen Leng
Project Manager: Susan Stuart
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Histology
AN ILLUSTRATED COLOUR TEXT
Barry S Mitchell BSc PhD MSc CSci FIBMS CBiol FIBiol

Dean, Faculty of Health and Life Sciences
De Montfort University
Leicester, UK
Sandra Peel BSc PhD DSc

Visiting Reader, Centre for Learning Anatomical Sciences
School of Medicine, University of Southampton
Southampton, UK
EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2009
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First published 2009
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v
Preface
Histology is more than just the science This book brings together high-quality The authors have long experience in
of microanatomy. It allows the examina- illustrations and a concise text focused teaching students of medicine and allied
tion of structures by using a variety of on essential features. It is ideal for healthcare professions. This has helped
microscopes, but it also enables one to modern medical undergraduate curri- to contextualise the information pre-
deduce much about the inner workings cula where basic sciences emphasise the sented. To this end, in each chapter
of cells, tissues and organs. It is funda- principal points of relevance to the ‘Clinical boxes’ give examples of how
mental to understanding structure and students. The book will also be useful for histological changes can be indicative of
function at all levels, providing essential other undergraduate science courses ageing or disease processes. The book
links between the gross dissections dealing with the structure and function should help ensure that once an under-
studied by anatomists, the functioning of animals other than humans. It will be standing of histology has been gained
of the whole body studied by phy- valuable to those requiring knowledge of the principles of disease processes may
siologists, and the abstract formulae histology at postgraduate level (in medi- readily be understood.
representing molecules studied by bio- cine or science). It should also show the
chemists. Histology therefore, under- potential for using histology to advance
pins medical studies and many other life research into the structure and function Barry Mitchell
and applied life science studies. of the body. Sandra Peel
vi
Acknowledgements
We are particularly fortunate to have have also used archived photographs Crossman AR, Neary D. Neuroanatomy:
had access to histological microscope of the slides, mostly taken by one An Illustrated Colour Text, 3rd edn.
slides, most of which were produced by of the authors. We are grateful to the Elsevier: 2005.
skilled staff of the Human Morphology Head of the School of Medicine, Univer- We are grateful to Dr M. Wood for
Group in the School of Medicine, Uni- sity of Southampton, Southampton, UK, her critical reading of the manuscript.
versity of Southampton, Southampton, for permission to use the photomicro-
UK. We are extremely grateful to them graphs. All (except one) were produced
for their work. at the University of Southampton.
We have taken photographs of these We thank the publishers for permis-
slides especially for this book and sion to use Fig. 6.4, which appeared in
vii
Contents
1. Introduction to histology 1
2. The cell 5
3. Primary tissues 1: epithelial tissue 13
4. Primary tissues 2: connective tissue 21
5. Primary tissues 3: muscle tissue 26
6. Primary tissues 4: nerve tissue 33
7. The skin 42
8. The blood and immune system 49
9. Bone and cartilage 59
10. The circulatory system 69
11. The respiratory system 77
12. The digestive system 83
13. The urinary system 97
14. The endocrine system 106
15. The male reproductive system 114
16. The female reproductive system 123
Glossary 133
Index 135
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1
Chapter 1
Introduction to histology
Histology is the study of the microscopic microscopes but contrast is limited and cells, etc. must be preserved. There are
structure and function of tissues. Tissue the cells rarely have around them the various methods for preservation, but a
is a general word used to describe the structures they had in the body. In standard way is to place samples of
components of animals (and plants), routine histology, very thin slices of tissue in a solution of formaldehyde as
and tissues consist of cells and the sur- tissues (5–10 μm thick) are prepared rapidly as possible after death or after
rounding support media (extracellular through which light can penetrate. To removing them from a living body. Form-
matrix). Historically, four primary tissue achieve sufficient contrast and colours aldehyde changes the conformational
types were categorised (in animals) by in the tissues so that they may be visu- state of the proteins (and other large
grouping together cells with similar alised, dyes or specific chemicals are molecules) and prevents enzymes from
form and function: they are epithelial applied to the slices of tissues. In these degrading the tissues: this process is
tissue, connective tissue, muscle tissue specimens, light microscopy can resolve known as fixation. This chemical fixa-
and nerve tissue. The cells within these detail of structures about 0.2 μm apart. tion can be compared with the process
categories of tissues may vary in struc- However, by using much thinner slices of boiling an egg in which heat changes
ture and be specialised according to and electrons instead of light, electron the conformational state of the proteins
their function and location. Most extra- microscopy can resolve detail down and, with enough boiling, the proteins
cellular matrix is derived from the cells to about 0.0002 μm. (Note 1 mm = in the white and yolk of the egg become
that it surrounds, and its composition is 1000 μm.) solid.
related to its function. For example, a Numerous advanced techniques, suit-
very dense, hard, extracellular matrix is able for light and electron microscopy,
Tissue processing for
formed by bone cells but, in contrast, may be used to identify specific mole-
slicing (sectioning)
the matrix in which blood cells flow is cules in tissues via their reaction with
fluid (although most blood cells do not labelled molecules. The labelled mole- Most body tissues are soft in life and
contribute to the fluid that supports cule is then detected, e.g. as colour using only a little harder after they have been
them). Various combinations of tissues ordinary light microscopy, as fluores- fixed in formaldehyde, so they are diffi-
form organs (e.g. the brain and liver), cence by viewing using ultraviolet light cult to slice thinly enough to be exam-
connecting structures (e.g. ligaments) or as radioactivity using photographic ined using a routine microscope. In
and packing material around organs film. Details of advanced techniques order to prepare thin slices, tissue
(e.g. around the kidney). In addition, for studying the components of tissues samples are impregnated with a sub-
various combinations of organs and with light and electron microscopes are stance which makes them solid. The
other structures form systems of the beyond the scope of this book and the medium used in routine histology to
body which together perform related reader is advised to consult other texts. confer rigidity is paraffin wax, which
functions (see Chapters 10–16). However, we give a brief overview below is liquid at about 58ºC but solid at
The unaided (good) eye can just about of basic histological techniques. room temperature. Wax and water-
see objects which are 200 μm in diame- based tissues are immiscible, so formal-
ter; very few cells are as big as this, dehyde-fixed tissue samples cannot be
Tissue preservation
although a very fine hair may be this impregnated directly with wax. Hence,
(fixation)
width. However, there are particular tissue samples are processed through a
challenges in examining structures If any piece of the living body is removed schedule which removes and replaces
smaller than 200 μm. Most components it begins to degenerate as cell death the water. This is most easily achieved
of tissues have little colour and contrast, occurs: this process is referred to as by transferring the tissue sample
and thus cells and the matrices sur- necrosis. In this process, enzymes in through gradually increasing concentra-
rounding them are indistinguishable if cells are released from their normal tions of alcohol which (at 100%) replaces
light is transmitted through them using location and break down the cells and all the water. Alcohol itself is also immis-
a basic light microscope. Indeed, light molecules in surrounding areas. Conse- cible with wax but it is replaced in the
will only penetrate thin slices of tissues quently, the precise three-dimensional tissue sample by processing it through
or thin layers of cells growing in vitro. arrangement of structures within, and increasing concentrations of a solvent
Various types of microscopes and surrounding, cells in life disappears. To that is miscible with alcohol and wax,
methods of preparing specimens for study the arrangement of molecules, e.g. chloroform or xylene. This solvent
examination have been developed. cells, extracellular matrix, tissues and in turn is removed by placing the tissue
Living, isolated, whole cells can be exam- organs as they were in life, necrosis sample in several changes of molten
ined using special (phase contrast) light must be prevented and the molecules, wax so that the wax infiltrates the tissue.
2 HISTOLOGY: AN ILLUSTRATED COLOUR TEXT
The sample in the molten wax is then scope slides ready for staining proce- appear as densely stained structures in
allowed to set and a solid block of wax dures to allow visualisation of the H&E-stained sections (Fig. 1.1). In some
forms in which the tissue sample is components of the tissue sample. instances, parts of the nuclei appear
embedded. The tissue is then ready for palely stained, and this indicates that the
sectioning. Given the toxicity of the sub- Methods for visualising DNA is uncoiled and was in active use
stances used in these processes, appro- tissues for light microscopy prior to fixation. In addition, in some
priate safety precautions must be palely stained nuclei a small, dense,
As most staining methods use dyes
taken. round region of staining may be appar-
soluble in water, wax-embedded tissue
Advanced techniques make use of a ent; this is a nucleolus (Fig. 1.1). The
sections have to be processed through
variety of solid support media, e.g. a dense staining, by haematoxylin, of
the reverse of the sequence of solvents
hard synthetic resin may be used to the RNA in a nucleolus indicates that
used to embed the tissues in order to
embed tissue samples and very thin sec- the cell was actively synthesising protein
remove the wax and return the tissue
tions (0.1 μm) cut and examined using (see Chapter 2). Cells synthesising large
sample to an aqueous solution.
an electron microscope. In addition, by amounts of protein also contain large
Many staining methods depend on
freezing a tissue sample immediately amounts of RNA in their cytoplasm, and
the chemical attraction of dyes for
after removing it from a living body an this too may be visualised as it will bind
particular molecular configurations in
instant support medium of ice is formed. haematoxylin and appear bluish purple
tissues. The most common technique
Sectioning can be done at sub-zero tem- (Fig. 1.1). In contrast, eosin is an acidic
used to demonstrate the general topog-
perature and provide histological prepa- dye and binds to bases. The proteins in
raphy of tissues uses the dyes haema-
rations which can be examined within the cytoplasm of many cells (Fig. 1.1)
toxylin and eosin (H&E). About half the
minutes of sampling. This is a routine and proteins in extracellular matrices
illustrations in this book are of photo-
process that is of use to surgeons in stain with eosin and appear red or
micrographs of sections stained with the
deciding how to proceed with an pinkish orange.
H&E method. Other illustrations are of
operation.
sections prepared using special methods
as indicated in the text and captions. Histochemistry and
immunohistochemistry
Tissue sectioning
H&E method In contrast to staining with dyes, histo-
Thin sections (slices) are cut using a Haematoxylin is a basic dye which binds chemistry and immunohistochemistry
microtome, a machine that holds an to acidic components in tissues, produc- techniques involve specific chemical
embedded tissue sample firmly in place ing a blue/purple colour. Typically, hae- or immunological reactions to detect
and cuts thin sections with a very sharp matoxylin binds to nuclei because of various components of tissues. For
blade. Typically, a wax-embedded tissue their content of deoxyribonucleic acid example, histochemistry can be used to
sample can be cut at 5 μm thick. The (DNA) and ribonucleic acid (RNA). detect types, and location, of carbohy-
sections are then placed on glass micro- Nuclei containing mostly inactive DNA drates (Fig. 1.2) and enzymes. Immuno-
histochemistry can detect molecules
that are antigens by applying labelled
antibodies that can be visualised using a
microscope. It is beyond the scope of
this book to detail the range of methods
available for demonstrating specific
molecules in tissues.
Cell with densely stained Illustrations in this book

nucleus and red cytoplasm
Most illustrations in this book were
photographed on a Zeiss or an Olympus
Cell with palely stained nucleus light microscope using lenses which
with densely stained nucleolus magnify between ×12 and ×120. (Some
and red cytoplasm blood cells were photographed using
lenses magnifying at about ×350.)
Some images were photographed using
colour-positive transparency film (about
10 × 13 cm), others using 35 mm film
Space (artefact) (negative and positive) and others using
a digital camera with optical magnifica-
tion of ×4 in addition to magnification
Nuclei of cells with cytoplasm by microscope lenses. Over half of the
stained purple with haematoxylin illustrations using light microscopy
were taken especially for this book. The
other images using light and electron
Densely stained nuclei of cells microscopy are from material prepared
with little cytoplasm and archived by the Human Morphol-
Fig. 1.1 Stomach. Routine wax-embedded section stained with haematoxylin and eosin. Medium ogy Group at the University of South-
magnification. ampton, Southampton, UK, and are
Introduction to histology 3
currently in the Centre for Learning through their largest diameter, so care if sliced close to an end rather than in
Anatomical Sciences, School of Medi- needs to be taken when assessing the the middle. Obliquely cut slices will
cine, University of Southampton. size of other structures in comparison produce solid ellipsoid shapes which
with red cells. will vary in shape and size depending on
Another challenge in interpreting the angle of cut. Histological sections on
Interpretation in histology
sections of tissues is that a variety of microscope slides have to be interpre-
One of the challenges in interpreting appearances may result from slicing ted by constructing possible three-
structure and function by studying hist- three-dimensional structures and exam- dimensional shapes from their two-
ological sections is how to assess the ining them as very thin slices, effectively dimensional appearance. For example,
size of objects viewed (when using a as two-dimensional structures. Consider if a hollow circular structure is seen in
microscope or viewing an illustration). slicing a curved, peeled banana (Fig. 1.4). a histological section it may be from a
If red blood cells can be identified, they Taking a slice along its length will show hollow sphere or part of a straight or
can be used as a rough scale to estimate the curve and that it is a solid object. coiled hollow tube cut at right angles to
the size of other structures as their Slicing at right angles to the length of a its length.
maximum diameter is about 7 μm (Fig. banana will produce circular (solid) Artefacts present other challenges in
1.3). Not all red cells will be sectioned slices which will be smaller in diameter interpreting histological sections. Arte-
facts are appearances in histological sec-
tions which are there as a consequence
of procedures used to prepare the tissue
sample. During fixation, e.g. with form-
aldehyde, many small water-soluble
molecules are not ‘fixed’ in place, and
even those molecules that are fixed in
place may shrink and pull away from
adjacent structures. Spaces seen in hist-
ological sections (Figs 1.1–1.3) have to
be assessed and their cause (artefact or
not) determined. Experience and know-
Lumen of small intestine ledge of the structures being examined
Carbohydrates in cytoplasm of a cell helps to identify the space in Fig. 1.1 as
an artefact. In contrast, the space in Fig.
1.2 is not an artefact: it is part of the
empty lumen of the small intestine.
Other empty spaces in tissue samples
may be due to the extraction of fat by
Fig. 1.2 Small intestine. Routine wax-embedded section stained with special stain which displays the organic solvents used in routine hist-
certain large carbohydrate molecules as blue/turquoise. High magnification. ological processing or to components
not reacting with the stains used. The
apparently large, empty spaces in Fig.
1.3 show the typical appearance of
adipose cells. These are cells in which
Cell membranes of adipocytes
a
Nucleus of adipocyte
a a
a
Red blood cell
b b b b
Cytoplasm of breast cells
c
Lumen (surrounded by breast cells)
Extracellular matrix
c c
‘Empty’ cytoplasm of adipocytes c
Fig. 1.3 Breast during lactation. Routine wax-embedded section stained with special stain which Fig. 1.4 A banana showing the appearance
shows extracellular proteins as blue. Red cells appear scarlet. Compare the size of the red cells with the of slices taken across various planes.
size of the adipose cells. (Adipose cells are some of the largest cells in the body and red cells are about Sections a–a and b–b are transverse sections and
7 μm in diameter.) Low magnification. section c–c is an oblique section.
fat occupies most of the cytoplasm.

Routine processing extracted the fat and
Summary
only the nucleus and membrane around ■ Histology is the study of the microscopic structure and function of tissues.
each adipose cell is seen. In Fig. 1.2, the ■ Components of the body are categorised as four tissue types: epithelial, connective, muscle
cells which have been stained blue due and nerve. Tissues comprise cells and extracellular material which carry out specific
to their carbohydrate content would functions.
have bound little or no H&E and would ■ Various combinations of tissues form organs and other components of the body.
thus have appeared empty in a routine In order to examine the microscopic structure of tissues, various procedures are necessary.
preparation. The routine processes for doing this are:
Another challenge presented, espe-
cially to histopathologists and research- ■ Fixation. Tissues are immersed in formaldehyde, which preserves the molecules and their
ers, is to decide whether the tissue structural arrangement in tissues as near as possible to how they were in life (and prevents
section examined is normal or abnor- necrosis).
mal. In some instances, if the tissue has ■ Processing. These stages replace the water with solvents that are miscible with molten wax.
not been fixed rapidly after death, necro- ■ Embedding. Tissues in molten wax are cooled and the solid wax supports the tissue.
sis occurs and this changes the appear- ■ Sectioning. Thin slices of wax-embedded tissue are cut and attached to microscope slides.
ance of the sectioned tissue. In addition, ■ Processing. This removes the wax and returns the tissues to an aqueous state.
histopathologists and researchers have ■ Staining. This allows tissue components to be visualised. Haematoxylin stains acidic
to be able to interpret the appearance of substances (e.g. DNA in nuclei) blue/purple and eosin stains basic substances (e.g. many
a tissue sample and consider the tissue cytoplasmic proteins) red/orange.
in relation to time in the context of the Interpretation of microscopic structure may involve assessing:
whole body. Interpreting what has gone
before may allow a diagnosis of a disease. ■ possible three-dimensional structures represented by a two-dimensional image
Predicting what might yet happen to a ■ the size and identity of structures (including their chemical composition) and their function
patient could be essential, especially if ■ whether any appearance is due to artefacts
the tissue sample shows signs of cancer. ■ the significance of time in respect of the tissue sample, e.g. does it show that if similar
Consider looking at a sliced hard boiled tissue remains in the body it could be harmful.
egg (described above as an example of
fixation). Consider the two-dimensional
slice of the egg in the context of time.
What would it have been like 20 or so
days earlier before boiling (fixation), or
what might it have become 20 days later
if it had not been boiled?
5
Chapter 2
The cell
Cells are the fundamental units of life. cell throughout the life of the individ- plasm may be clearly distinguished
Textbooks may describe a ‘typical’ cell, ual. Cells undergoing successive rounds using a light microscope to examine
but such a cell does not exist. Most cells of mitosis are described as passing cells in slices of tissue (Chapter 1), to
are, to some extent, specialised in terms through a series of events known as the resolve finer detail an electron micro-
of their structure and function. Accord- cell cycle (see below). Other cells may scope may be used. As the wavelength
ingly, the structural appearance of cells reach an end stage of differentiation and of electrons is much shorter than light
can provide information about their become unable to undergo mitosis waves, electron microscopy can resolve
function. The term used to describe how and replicate themselves further. For structures about 1000 times smaller
cells are specialised is ‘differentiation’. example, shortly after birth nerve than the light microscope can. Within
Most cells have a nucleus which con- cells (neurons) cease division and cytoplasm, electron microscopy reveals
tains molecular programmes encoded replication. a range of membrane-bound organelles
in DNA (in chromosomes) that direct Despite there being no ‘typical’ cell, and other structures (Fig. 2.1) which
how a cell differentiates and what cells share certain characteristics. All carry out a variety of functions during
function(s) it performs. Many types of have a cell membrane which encloses the life of a cell. The term ‘ultra-
cell, even some which are differenti- cytoplasm; in most cells, the cytoplasm structure’ is used to describe structures
ated, also have the ability to replicate surrounds a nucleus. (Mature red blood revealed by electron microscopy. A brief
themselves by a process of cell division cells in humans do not have a nucleus, survey of the ultrastructure of cells in
known as mitosis (see below). Mitotic nevertheless they live for about 100 relation to their function is given
activity may continue in many types of days.) Although the nucleus and cyto- below.
Cell membrane
Cytoplasm
Nuclear membrane
Nucleolus
Organelle
Euchromatin of nucleus
Organelles
Cell membrane
Cytoplasm of adjacent cell
Fig. 2.1 Electron micrograph of a cell. Low magnification.

Ultrastructure of cells and

extracellular matrix
Cell membrane
All cells are surrounded by a cell
(plasma) membrane, and its integrity is
essential for the life of the cell. The cell Heterochromatin of nucleus
membrane is a double-layered lipid–
protein structure which has specific
molecules embedded in it at intervals: Cytoplasm
the type of molecule(s) varies with
the function of the cell. Most of the
organelles within cells are surrounded Collagen fibres (sectioned across
by a similar lipid–protein membrane. their length)
The cell membrane is semi-permeable
and allows inward and outward passage
of selected substances. It also forms an
essential barrier to the exterior and a
boundary for the internal structure of
the cell. It may be involved in attach- Collagen fibres (sectioned along
their length)
ments to adjacent cells (see below) and
in recognition and communication
within and outside the cell. Within, it
may communicate with its cytoplasm
and some signals may pass to the
nucleus. Outside, it may communicate
with other ‘self ’ cells, both normal and
abnormal (e.g. tumour cells or virally
infected cells). Many cells interact, via
Extracellular matrix
their cell membrane, with microbes, and
various molecules foreign to the body
and a variety of cellular activities are
stimulated or inhibited as a result.
Nucleus and nucleolus

The nucleus contains the vast majority
of the DNA of the cell. The DNA is the
hereditary material that has the genetic
code expressed in a double strand of
DNA in each chromosome. (Chromo- Cytoplasm
somes contain proteins as well as DNA.) Fig. 2.2 Electron micrograph of a cell. Low magnification.
The number of chromosomes in a
typical cell is species specific (humans
have 46). Human chromosomes com-
prise 22 homologous pairs and a pair of and RNA) travel between nucleus and heterochromatin the DNA molecules
sex chromosomes (two X chromosomes cytoplasm by this route. are coiled and condensed and appear
in females and an X and a Y chromo- The appearance of nuclei varies in dense. The DNA in heterochromatin is
some in males). One of each pair of relation to their function. Individual mostly inactive, i.e. not directing the syn-
chromosomes is derived from the moth- chromosomes are not apparent in cells thesis of RNA.
er’s oocyte and the other from the unless the cell is dividing. The nuclear One or more nucleoli also appear as
father’s spermatozoon (see, respectively, material, comprising DNA, proteins and densely stained regions in the nuclei of
Chapters 16 and 15). The nucleus may RNA, is known as chromatin and two cells actively synthesising proteins: their
also contain the structural and mole- types are described, euchromatin and position may appear central or periph-
cular mechanisms for the synthesis of heterochromatin. Euchromatin appears eral (Fig. 2.1). RNA molecules synthe-
RNA in one or more nucleoli. less dense than heterochromatin (Figs sised in the nucleolus leave the nucleus,
The nucleus is enclosed by a nuclear 2.1 and 2.2). The DNA molecules in via pores in the nuclear membrane, and
membrane which is formed by two euchromatin are uncoiled and are being are involved in organising protein syn-
plasma membranes. In places, the used as coding for RNA synthesis which, thesis in the cytoplasm.
nuclear membrane is perforated by in turn, directs protein synthesis in the
pores which allow transport of material cytoplasm. A large amount of euchro- Cytoplasm
to and from the nucleus. The outer matin in a nucleus (Fig. 2.1) indicates Cytoplasm comprises a fluid matrix, a
nuclear membrane is continuous in that a wide variety of RNA molecules cytoskeleton, various membrane-bound
places with some membranes in the are being made (and types of protein organelles and may include stored
cytoplasm, and molecules (e.g. proteins produced as a result). In contrast, in molecules.
The cell 7
Cytoskeleton process which extends several sion of energy for cellular processes,
The cytoskeleton of cells has several centimetres (Chapter 6). Other synthesis and secretion of protein,
types of structure which affect the shape microtubules assist in maintaining carbohydrate and lipid-based molecules,
of the cells, e.g. tubular structures (cen- cell shape, compartmentalising the storage of proteins and degradation of
trosomes and microtubules) and protein cytoplasm or facilitating movement waste material.
filaments (intermediate and thin). of organelles within the cytoplasm.
Microtubules are present in cilia, Mitochondria
■ Centrosomes (Fig. 2.3). These contain
and in cells undergoing division (see Mitochondria vary in shape but many
paired units, known as centrioles,
below). are ovoid (Figs 2.4 and 2.5). They are
which are set at right angles to each
■ Intermediate filaments. The main role surrounded by an outer and inner mem-
other and which contain nine triplets
of this group of filaments involves brane and provide most of the energy
of microtubules (see below). Centriole
resisting external stresses on the needs of the cell. The outer membrane
tubules anchor other microtubules.
cytoplasm by their attachment to is a typical plasma membrane, but the
■ Microtubules. Some microtubules are
specific internal cell structures. They inner membrane has numerous in-
straight and long and allow the
include the protein keratin in the foldings known as cristae. These folds
passage of substances within the cell.
epithelium of skin (Chapter 7). increase the surface area inside each
Many microtubules are polarised, i.e.
■ Thin (micro) filaments. These mitochondrion and provide a matrix in
they have specific ends with one end
filaments are formed from the which metabolic processes occur. The
usually attached to a centrosome.
protein actin. Actin filaments are matrix comprises a viscous fluid con-
Microtubules in some nerve cells
present in most cells and are taining enzymes associated with the tri-
transport molecules in a cytoplasmic
involved in moving organelles within carboxylic acid (TCA) cycle. Mitochondria
cells, in cell movement, and are involved in oxidative phosphoryla-
exocytosis and endocytosis (see tion, which results in the production
A Microtubule below). One specific role of actin in of adenosine triphosphate (ATP). ATP
muscle cells involves interaction with acts as a store of energy that is used
Centriole thicker protein filaments of myosin, for various cell activities. Mitochondria
which results in muscle contraction contain very small amounts of DNA in
(Chapter 5). the matrix which code for some mito-
chondrial proteins.
Cytoplasmic organelles
The main cytoplasmic organelles are Endoplasmic reticulum
mitochondria, endoplasmic reticulum, Endoplasmic reticulum is a membrane
Golgi apparatus, vesicles and lysosomes. system similar in appearance to the
These organelles are involved in provi- plasma membrane. It is double layered
Centriole
B
Microtubule
Membrane of RER
Outer membrane of mitochondrion

Fig. 2.3 The structure of centrosomes
sectioned (A) longitudinally through the Crista
paired centrioles (only some of the
microtubules are in the plane of this
diagram) and (B) a centriole sectioned
transversely.
Outer membrane
Mitochondrion
Matrix
Inner membrane Cistern of RER
Membrane of RER
Crista
Fig. 2.4 A cut open mitochondrion and its Fig. 2.5 Mitochondrion and rough endoplasmic reticulum (RER). Electron micrograph of part of
three-dimensional structure. a cell. Medium magnification.
and encloses a space known as a cistern (Fig. 2.5), others lie free or form (and their bound target molecules)
(Fig. 2.5). In cells actively synthesising clusters in the cytoplasm (Fig. 2.6). invaginates and takes in the bound mol-
molecules, the cistern may be relatively Specific proteins are synthesised by ecules; this process is known as recep-
wide. All membranes in the cytoplasm ribosomes from amino acids. The tor-mediated endocytosis (Fig. 2.6). The
of a cell are probably linked and some specificity is determined by coded fate of endocytotic vesicles varies; some
link to the nuclear membrane. Two RNA arriving from the DNA in the may fuse with lysosomes (see below) or
types of endoplasmic reticulum are nucleus. In general, proteins pro- the contents may have a specific use
described according to their appearance duced on RER are for export and within the cell. Exocytosis is the process
in electron micrographs. those produced by free ribosomes by which the contents of membrane-
are for internal use. bound vesicles are released from a cell.
■ Smooth endoplasmic reticulum (SER). The membrane around the vesicle fuses
These membranes appear smooth Vesicles, endocytosis with the cell membrane and the con-
and are sparse in cells except those and exocytosis tents of the vesicle are released from the
synthesising lipids such as steroid Membrane-bound vesicles are usually cell (Fig. 2.6).
hormones (Chapters 14–16). In spherical. Many are involved in taking
some muscle cells, SER is especially substances into and out of cells by the
important as it moves calcium ions processes of endocytosis and exocytosis Golgi apparatus
which are essential for muscle respectively (Fig. 2.6). It is usual to dis- The Golgi apparatus involves a stack of
contraction (Chapter 5). tinguish two types of endocytosis: pino- several parallel membranes (lying close
■ Rough endoplasmic reticulum (RER). cytosis involves the uptake of fluid and to RER) and small membrane-bound
These membranes appear rough phagocytosis the uptake of solids (but vesicles (Fig. 2.6). Newly synthesised
(Fig. 2.5) as they are studded with fluid may enter in the same vesicle). In proteins pass in vesicles from RER to
ribosomes (see below). They are addition, the process of endocytosis the Golgi membranes. The proteins (in
particularly prominent in cells may be non-specific or specific. In non- vesicles) then pass between the layers of
synthesising proteins for export specific endocytosis the cell membrane Golgi membranes. During the time
from the cell. Some proteins becomes invaginated and then encloses spent in the Golgi apparatus various car-
synthesised on RER are passed to some extracellular material. Specific bohydrate molecules may be added to
the Golgi apparatus for further endocytosis involves receptor molecules the newly synthesised proteins. Vesicles
processing (see below). on the cell membrane that are able to leaving the Golgi stack may move
■ Ribosomes are electron-dense struc- bind specific (target) molecules. In spe- towards the cell membrane and dis-
tures containing RNA; some are cific endocytosis only the part of the cell charge their contents by exocytosis or
attached to the membranes of RER membrane with the receptor molecules release them for internal use; others
Fig. 2.6 Endocytosis, exocytosis, and function

of rough endoplasmic reticulum (RER), Golgi
Extracellular and lysosomes. Arrows (within the cell) indicate
fluid
movement of structures as the various functions
Phagocytosis occur.
of solids
Non-specific
endocytosis
Nucleus
Nucleolus RER making
Cytoplasm proteins
for export
Receptor-
mediated
endocytosis
Exocytosis of
modified protein
Ribosomes
making proteins
for internal use Membrane-bound
modified proteins
Golgi from Golgi
RER making Lysosome function
proteins
Receptor in Cell debris, dead
membrane bacteria, carbon
Target molecule Primary lysosome
Secondary lysosome
Secondary lysosome
The cell 9
may remain stored in vesicles in the cell Cytoplasmic processes (Fig. 2.8). The tubules are involved in
until they are needed. The cytoplasm of some cells forms spe- moving the cilia in a regular,
cific processes which extend from the synchronised beat which propels the
Lysosomes cells. These are microvilli, cilia and material on the surface of the
Lysosomes are membrane-bound flagella. ciliated cells in a particular direction
organelles (Fig. 2.6) which are usually (Chapter 11).
electron dense and thus appear dark in ■ Microvilli (Fig. 2.7) project as finger- ■ Flagella are similar to cilia and have
electron micrographs. They are formed like cytoplasmic extensions from symmetrically arranged microtubules
via Golgi bodies and contain hydrolytic many epithelial cells, e.g. from the but are much longer and wider than
enzymes which are active at low (acidic) apical surface of cells lining some gut cilia. In humans, the only cells which
pH (e.g. acid phosphatases). Newly tubes and others lining some tubules have a flagellum are spermatozoa
formed lysosomes are known as primary in the kidney. Actin microfilaments (the male gametes). Each
lysosomes and they may remain in a cell in microvilli help maintain their spermatozoon is propelled by the
for some time before they become active. shape. The microvilli increase the beating of its flagellum as it travels
Lysosomes function by fusing with some area of cell membrane in contact the length of the female reproductive
endocytotic vesicles, other organelles or with the contents of the tube and this tract after copulation (Chapters 15
fragments of organelles, or other mate- aids absorption of molecules from and 16).
rial; at this stage they become secondary the tube into the cell.
lysosomes (Fig. 2.6). Lysosomal enzymes ■ Cilia are cytoplasmic processes Molecules stored in cytoplasm
are released onto the ingested material which extend from the cell Carbohydrates and lipids are stored in
and break down most of the molecules membranes of some epithelial cells, cytoplasm; most are not enclosed by a
they contained. The small molecules e.g. cells in the epithelium lining membrane. Glycogen is stored in many
formed as a result may be reused by the tubes transporting air to the lungs. cells and acts as an energy reserve. It
cell; other substances which resist diges- Cilia are usually wider and longer appears as dense particles in electron
tion (e.g. carbon) remain in the lyso- than microvilli. Cilia have micrographs, some of which are clus-
some. The integrity of the membrane microtubules extending along their tered together and may occupy exten-
around lysosomes is important as it length which have a symmetrical sive regions of the cytoplasm. Lipids are
ensures that the hydrolytic lysosomal arrangement. The microtubules are stored in some cells generally as spheri-
enzymes do not pass into the cytoplasm in a 9 + 2 pattern, which is apparent cal masses. Some stored lipids act as
and destroy the cell itself. when sectioned across their length precursor molecules for the synthesis of
steroid hormones, others provide energy
reserves. Proteins and glycoproteins are
usually stored in membrane-bound vesi-
cles and their contents discharged by
exocytosis when needed.
Intercellular junctions
Microvilli There are three specialised ways in
which adjacent cells are attached to each
other (Fig. 2.9).
Cytoplasm at apices of cells ■ Tight junctions (zona occludens). In

these junctions a short length of the
outer cell membrane layers of
adjacent cells is fused. These
junctions prevent molecules from
passing in between cells.
Heterochromatin of nucleus
Euchromatin of nucleus
Microtubule
pair
Fig. 2.8 The symmetrical arrangement of
Fig. 2.7 Microvilli projecting from the apical surface of cells. Electron micrograph of cells. Low microtubules (nine pairs + two) in a cilium
magnification. sectioned across its length.
■ Desmosomes (macula and zonula Tight junction 1h G0

adherens). These junctions are points M
(maculae) or encircling bands 4h
G2
(zonulae) which appear in electron
micrographs as dense regions
between adjacent cell membranes. On Cytoplasm of Cell membrane
part of two (double layer) Cell cycle G1 12h
the inside of the cell membrane in adjacent cells of one cell
the region of a desmosome there is a
dense plaque and components of the Desmosome S
cytoskeleton. Desmosomes provide 6–8h
firm physical attachments between
cells but do not prevent molecules
G1 = Gap phase
moving in between the cells. (no DNA synthesis)
Interphase
■ Hemidesmosomes are similar to S = DNA synthesis occurs
desmosomes, but they are one G2 = Gap phase
(no DNA synthesis)
sided; the cell membrane interacts
Gap junction M = Mitosis completes cell cycle
with extracellular material. G0 = Quiescent; either permanently
■ Gap junctions. At these junctions non-dividing or cells able to
membranes from adjacent cells are resume cell division
closely applied but they are not Fig. 2.10 The phases of the cell cycle.
fused. Gap junctions allow the
passage of ions and very small Fig. 2.9 The structure of cell junctions. Blue
arrows show the passages along which ions
molecules from one cell to an
travel in gap junctions.
adjacent cell. They are particularly two parallel chromatids joined at a
important between heart muscle point known as the centromere.
cells as ion movement between such Each chromatid contains an old
mitosis, cells enter the G1 phase, which
cells is an essential part of strand of DNA and the newly
is often the longest phase of the cycle.
coordinating contraction of heart synthesised copy strand. At this
During G1, cells synthesise many mole-
muscle (Chapter 10). time, the centrosome of the cell has
cules, increase the volume of the cyto-
been duplicated and they move to
plasm and increase the number of
opposite poles of the cell. Part of
Extracellular matrix organelles. These synthetic processes
each centrosome begins to give rise
Many cells are adjacent to extracellular may be specific for a cell to carry out its
to an array of microtubules which
matrix and some are entirely surrounded functions as well as to produce mole-
will form a mitotic spindle (see
by it. Extracellular matrix varies in form cules necessary for the next phase. At
below).
and function in different parts of the the end of G1, the cells move into the
■ Prometaphase. This stage begins with
body (Chapter 4). Some proteins (e.g. next phase (the S phase) when they
the disappearance of the nuclear
collagen) form fibres in extracellular begin to synthesise new DNA. During
membrane. During this phase
matrix, and their appearance depends the S phase the new DNA is assembled
chromosomes are still randomly
on the angle at which they are sectioned along the length of the existing double
arranged in the cytoplasm. A mitotic
(Fig. 2.2). strand of DNA in each chromosome by
spindle forms and each chromosome
the process of base pairing; this dupli-
begins to move towards the
cates the existing DNA. At the end of the
microtubules at the equator of the
The cell cycle and S phase, instead of a double strand of
spindle.
cell division DNA in each chromosome there are
■ Metaphase. In this stage (Fig. 2.11B)
four strands of DNA (arranged as two
The cell cycle is the series of stages each chromosome attaches (by its
chromatids). When DNA replication is
through which a cell passes between centromere) at a separate point on
completed, the cells move into the G2
successive rounds of the cell division the equator of the spindle, an
phase, which is when the cell prepares
process known as mitosis (Fig. 2.10). The arrangement described as forming a
for mitosis. The G2 phase is usually
actual event of mitosis takes a relatively metaphase plate. Such plates are
much shorter than the G1 phase.
short time in the cycle, sometimes less readily visible with the light
A cell which undergoes a mitotic cell
than an hour. The stages a cell passes microscope in actively dividing
division becomes two identical offspring
through before successive mitotic divi- cells.
cells with the same number of chromo-
sions are collectively known as inter- ■ Anaphase. During anaphase the
somes containing the same amount and
phase and take considerably longer chromosomes split along their
type of DNA as the original cell. Mitosis
(several hours or days). During inter- length separating the two
may be described in five stages.
phase, events occur which may relate to chromatids which then move away
the specific functions of the cell, e.g. ■ Prophase. During this stage the DNA from each other and towards
protein synthesis and secretion. A cell in in chromosomes becomes very opposite poles of the spindle (Fig.
interphase must also undergo specific coiled and condensed and appears as 2.11C). The separation of the
processes to replicate its DNA in prepa- very dense chromatin. The nucleolus chromatids follows the track of the
ration for mitosis. disappears and RNA production microtubules of the spindle.
The interphase of the cell cycle is ceases. Towards the end of prophase Towards the end of anaphase a
divided into three stages (Fig. 2.10). After (Fig. 2.11A) chromosomes appear as depression begins to develop around
The cell 11
A
Nuclear membrane
Cell membrane Cytoplasm
Centromere of
Y chromosome
Homologous pair X chromosome

of chromosomes
Centromere of
chromosome
Centrosome
Represents old DNA in a chromatid

Represents new DNA (paired alongside
old DNA in S phase of cell cycle)
B C
Cytoplasm Cytoplasm
Cell membrane
Cleavage
furrow
Equator of
mitotic spindle
Cleavage
Microtubules of furrow
mitotic spindle
Centrosome Centrosome
Fig. 2.11 (A) Late prophase, (B) metaphase and (C) anaphase stages of mitosis. Only one pair of homologous chromosomes (of the 22 pairs in
humans) and an X and a Y chromosome are shown. In (C) arrows show the direction of movement of the chromatids.
the cytoplasm and it is known as the

cleavage furrow.
■ Telophase. The chromatids reach the
opposite poles of the spindle and Cell membrane
the spindle disappears. The furrow
in the cytoplasm deepens and splits
the cytoplasm as cell membranes Chromatids in new cell
appear between the two new
offspring cells, a process known as
cytokinesis (Fig. 2.12). Each new cell
contains chromatids (each
containing double-stranded DNA) Reformed cell membranes
which are exact copies of the DNA
in the original chromosome. Each
chromatid is now a new
chromosome. These chromosomes
uncoil and appear as chromatin as a Chromatids in new cell
nuclear membrane develops,
surrounds the chromatin and Cell membrane
reforms the nucleus.
Fig. 2.12 Electron micrograph of a cell in the telophase stage of mitosis. The cell membrane
On completion of the cell cycle, the has formed around each new cell and completed cytokinesis. The nuclear membrane has not yet
two new cells may enter a G1 phase and reformed. Although all of the chromatids (i.e. new chromosomes) do not lie in the plane of section,
prepare for further rounds of the cycle. they appear as densely stained clumps and have yet to uncoil. Low magnification.
Some cells may suspend their progres-

sion around the cell cycle (usually at the
Summary
G1 stage) and enter a G0 phase (Fig. 2.10). ■ A cell is the basic unit of life formed from cytoplasm and a nucleus (in most cells) enclosed
Some cells in the G0 phase may eventu- by a cell membrane.
ally re-enter the cycle and replicate ■ The nucleus contains DNA (in chromosomes), proteins and RNA.
themselves when, for example, they are ■ In non-dividing cells, nuclear contents are described as chromatin:
needed to replace dead or damaged ■ heterochromatin is densely stained and is largely inactive
similar cells. Other cells halt their pro- ■ euchromatin is palely stained as the DNA is uncoiled and coding RNA to direct protein
gression around the cycle, undergo dif- synthesis

ferentiation and carry out specific ■ a nucleolus is present in nuclei of cells producing RNA.
functions before they die without having ■ Cytoplasm contains organelles which carry out specific functions:
divided again. ■ tubules and protein filaments give shape to cells and aid movement (of material in cells
and of cells themselves)
Meiosis ■ mitochondria provide energy (ATP) for the cell
Meiosis is a type of cell division in which ■ endoplasmic reticulum, which is formed from membranes surrounding a cistern, is
the number of chromosomes (and involved in synthesis. RER has bound ribosomes and synthesises proteins mainly for
DNA) in the offspring cells is half that export; SER is involved in lipid synthesis. Free ribosomes synthesise proteins mainly for
in the parent cell. This occurs only in internal use
the formation of gametes, i.e. ova in ■ membrane-bound vesicles are involved in uptake of substances into the cell
females and spermatozoa in males. (endocytosis) and export of substances (exocytosis)

Meiosis ensures that on fertilisation the ■ the Golgi apparatus has membranes and vesicles and modifies synthesised proteins by
normal number of chromosomes (and adding, for example, carbohydrates

their DNA content) is present in the fer- ■ lysosomes are membrane bound and contain hydrolytic enzymes. Lysosomes fuse with
tilised ovum (the zygote). The process of endocytotic vesicles and digest their contents.
meiosis ensures that there is a mixing of ■ Cytoplasm in some cells forms projections, for example cilia and microvilli, and may store
maternally and paternally derived chro- carbohydrate, lipids or proteins.
mosomes (and thus genes). This ensures ■ Specialised parts of cell membranes of adjacent cells form junctions which help to bind the
diversity of the gene pool of a species. cells together, prevent molecules moving in between the cells, or aid movement of ions
Further details of meiosis are described between adjacent cells.
in Chapters 15 and 16. ■ Cell division (mitosis) occurs in many types of cell. Prior to mitosis, cells synthesise copy
strands of their DNA in the S phase of the cell cycle:
■ In the prophase stage of mitosis chromosomes condense and become visible as
individual units. A spindle forms of microtubules. Gradually, the nuclear membrane
disappears and (at metaphase) the chromosomes move to the equator of the spindle
and attach to the microtubules. In the next phase (anaphase) the chromosomes split
along their length and each half moves towards a pole of the spindle. Mitosis ends with
telophase as the spindle disappears and the nuclear membrane reforms and encloses
the uncoiling chromosomes. The cytoplasm of the original cell splits and two new cells
are formed with each having the same number of chromosomes (and amount of DNA)
as the original cell.
13
Chapter 3
Primary tissues 1: epithelial tissue
detecting some sensations. Although ■ compound (stratified) epithelia, which

Introduction to epithelia exhibit a variety of forms and display several layers of cells.
primary issues functions they all consist of epithelial
In each of these categories there are
The microscopic structures of the body cells which are tightly bound to each
sub-categories, classified according to
were classified originally into four other by specialised junctions (Chapter
the shape of the epithelial cells.
primary tissues: 2). The importance of epithelia to body
function is apparent when it is realised
■ epithelial tissue Simple epithelia
that every molecule or organism that
■ connective tissue In simple epithelia, each epithelial cell
enters (or leaves) the body has to pass
■ muscle tissue is attached to a basement membrane
through an epithelium.
■ nerve tissue. (sometimes called a basal lamina). The
basement membrane is a concentration
This classification is still in wide use Epithelia lining and
of extracellular material, including
and is the basis for all studies aimed at covering structures
glycoproteins and connective tissue
understanding the structure and func- Epithelia are categorised as:
fibres (mainly collagen) (Chapter 4).
tion of normal and abnormal cells, ■ simple epithelia, which consist of a Simple epithelia comprise four main
tissues and organs of the body. single layer of epithelial cells types:
Epithelial tissues in general lie on sur-
faces (epi = on or upon) and many carry
out secretory and other highly spe-
cialised functions. Cells from some A C
Cell boundary Cell boundary
epithelia migrate from surfaces during Lumen
development in utero and form glands Lumen
within the body (e.g. the pancreas) and
produce and secrete various molecules.
The names of the other primary tissues Basement
(connective, muscle and nerve) indicate membrane
Simple squamous Basement
the prime functions of the components membrane
epithelial cell cytoplasm
of these tissues in their titles, respec-
Simple squamous Columnar epithelial
tively the connection of structures, con- cell nucleus Columnar epithelial cell cytoplasm
traction of muscles and conduction of cell nucleus
B
nerve impulses. Cell boundary
D Cilia
Lumen Goblet cell
(mucus in cytoplasm)
Epithelial tissue
Epithelial tissue consists mainly of epi-
thelial cells which form layers (epithe-
lia) covering the body and structures in Basement
membrane
the body such as organs. Epithelial
tissues also form the linings of hollow Cuboidal epithelial
cell cytoplasm
structures in the body and form the
Cuboidal epithelial
outer layer(s) of some membranes. Epi- cell nucleus
thelial cells are the major cell type Goblet cell
forming the parenchyma of some solid nucleus
organs and glands and are involved in Basement
membrane
synthesising and secreting many sub-
stances. In addition to secretion, epithe- Nucleus Pseudostratified
columnar
lia are involved in a variety of functions, epithelial cell
including transport of substances, Fig. 3.1 Simple epithelia. (A) Simple squamous epithelium, (B) simple cuboidal epithelium, (C)
absorption of molecules, modulation of simple columnar epithelium and (D) pseudostratified epithelium (with ciliated columnar epithelial cells
permeability and protection, and in and goblet cells).
■ simple squamous Connective tissue

■ simple cuboidal
■ simple columnar
■ pseudostratified columnar.
Squamous epithelial cell nucleus
Simple squamous epithelia

Squamous epithelial cells are irregularly
shaped, flattened (pavement like) and fit
intimately together. The nuclei in squa-
Connective tissue cell nucleus
mous cells often occupy a central posi-
tion, and, given that the cytoplasm of the
cells is generally flattened, a bulge may
be apparent in the region of the nucleus
(Fig. 3.1A). An important function of
simple, squamous epithelial cells is that
they facilitate the transport of gases Lumen of blood vessel
and/or other substances across the epi-
thelium. Examples of the location of
squamous epithelia include the linings
of blood vessels (Fig. 3.2), which are Squamous epithelial cell nucleus
known as endothelia, and the walls of
lung alveoli, i.e. regions where the move-
ment of oxygen and carbon dioxide is Connective tissue cell nucleus
important.
Simple cuboidal epithelia Fig. 3.2 Simple squamous epithelium, lining a blood vessel. The squamous cells lining blood
Epithelial cells in cuboidal epithelia are vessels are known as endothelial cells; they may appear so flattened that it is not possible to distinguish
shaped like boxes, with fairly square the extent of the cytoplasm (even at this magnification). The nuclei may appear to protrude into the
profiles, and each cell has a roughly cen- lumen with no intervening cytoplasm. Adjacent connective tissue supports the endothelium. Very high
trally placed nucleus. Unlike squamous magnification.
cells, their nuclei do not bulge as there
is ample cytoplasm around them (Fig.
3.1B). Examples of where this cell type
may be found include the lining of the
walls of ducts in the liver (Fig. 3.3) and
the walls of ducts draining glands, e.g.
sweat glands. Their function varies with Cuboidal epithelial cell nucleus
their location and may involve synthesis
and secretion, or excretion, or absorp-
tion of molecules.
Simple columnar epithelia

Columnar epithelial cells have the shape Lumen of duct
of columns with their longest dimen-
sion at right angles to the basement
Cuboidal epithelial cell nucleus
membrane. Their nuclei typically lie
near the basement membrane (Fig. 3.1C)
or about half-way along their length.
Columnar epithelial cells are present
in the lining of the wall of the gastroin-
testinal tract (Fig. 3.4), the gall bladder Liver cell nucleus
and some tubules in the kidney, for
example. In many locations, they are
associated with the function of absorp-
tion of substances into the cells across
their apical (luminal) surface and then
out of the cells via the basal surface and
then across their basement membrane.
The apical surfaces of many absorp-
tive columnar epithelial cells display a
‘brush border’ appearance (Fig. 3.4)
when examined by light microscopy
and this is due to the presence of micro- Fig. 3.3 Simple cuboidal epithelium, lining a bile duct in the liver. Connective tissue is stained
villi (Chapter 2). The microvilli increase blue. Special stain. High magnification.
Primary tissues 1: epithelial tissue 15
from abrasion. The squamous surface

cells are shed, especially when abrasion
occurs, but they are replaced by deeper
Lumen cells which become flattened as they
move to the surface layer. Cells located
at the base of the epithelium are the
progenitor (stem) cells for the rest of the
epithelial cells. Mitosis of these stem
Brush border cells ensures that the layers of cells are
constantly replaced as some new cells
migrate to the surface. Importantly,
some cells remain in the basal layer and
continue to function as stem cells.
The cells in a specialised type of strati-
fied squamous epithelium produce
the protein keratin. The epithelium of
the skin, known as the epidermis, is the
Columnar epithelial cell nuclei main region of the body where this type
of epithelium is present and it is catego-
rised as a keratinised, stratified, squa-
mous epithelium (Fig. 3.7). The keratin
produced by the epithelial cells (kerati-
Cytoplasm of columnar nocytes) fills the cells in the upper layers
epithelial cell of the epidermis and these cells become
Brush border flattened and they die. Keratin from the
dead cells forms the surface layers of the
skin and it gradually flakes off (desqua-
mates). Keratin makes the skin water-
proof, reduces water loss by evaporation,
provides protection from abrasion, and
Connective tissue
resists the penetration of the skin by
Fig. 3.4 Simple columnar epithelium, lining the small intestine. The cytoplasm of columnar
epithelial cells, sectioned along their length, extends beyond their nuclei towards the apical (luminal) many molecules and microorganisms.
surface. In some cells, the apical surface displays a brush border. High magnification.
Stratified cuboidal epithelia
The surface cells of stratified cuboidal
the surface area of the luminal mem- a whiplash, and this moves the mucus epithelia are cuboidal in shape and
brane of absorptive cells and thus and its contents. The general direction usually only two layers are present. This
increase the efficiency of the transport of flow of the mucus is away from the type of epithelium lines ducts draining
of molecules. lungs and towards the pharynx where some glands, e.g. salivary glands.
most is swallowed.
Pseudostratified columnar Stratified columnar epithelia
epithelia Compound (stratified) epithelia This type of epithelium is present in
This type of epithelium is called ‘pseudo- Compound (stratified) epithelia are only a few locations in the body, e.g.
stratified’ because it appears as though composed of several layers of cells. some large ducts and portions of the
it is composed of several layers but each Only cells in the deepest layer are male urethra. Its deepest layer is typi-
cell actually has an attachment to the attached to the basement membrane. cally low cuboidal and the surface cells
basement membrane (Fig. 3.1D). The Sub-categories are classified according are columnar in shape.
appearance of stratification is because to the shape of the surface epithelial
the nuclei in the various cells in the epi- cells: Transitional epithelium
thelium are located at different levels in This type of epithelium is a highly spe-
■ stratified squamous
relation to the basement membrane and cialised stratified epithelium present
■ stratified cuboidal
a single section through the cells does only in the regions of the body in contact
■ stratified columnar
not usually display the whole extent of with urine. Transitional epithelium lines
■ transitional.
their cytoplasm. This type of epithelium parts of the kidney, the ureters, the
lines much of the respiratory tract (Fig. Stratified squamous epithelia urinary bladder (Fig. 3.8) and parts of
3.5). Specialised epithelial cells are Stratified squamous epithelia have the urethra (Chapter 13). A key function
present in this ‘respiratory’ epithelium; layers of cells of cuboidal or columnar of transitional epithelium is its ability
some produce mucus (unicellular glands shape but the surface cells are squamous to act as a permeability barrier between
known as goblet cells) and others have (flattened and pavement like). Typical hypertonic urine and isotonic tissue
cytoplasmic projections on their luminal regions of the body where stratified fluid and blood. In addition, the transi-
surface known as cilia (Chapter 2). squamous epithelia are present include tional epithelium lining the bladder is
Together, cilia and mucus entrap solid the linings of the oesophagus, vagina able to stretch as the bladder distends
particles, e.g. dust and bacteria. The cilia (Fig. 3.6) and anal canal where the epi- and stores urine. The appearance of
move in a synchronised beat, a bit like thelia provide some physical protection transitional epithelium depends on the
Fig. 3.5 Pseudostratified columnar Connective tissue

epithelium lining the respiratory tract. The
nuclei of the epithelial cells appear to be in layers.
The cytoplasm of goblet cells is relatively palely
stained as they are filled with carbohydrates
which do not react strongly with haematoxylin
and eosin. The luminal surface of ciliated Goblet cell cytoplasm
columnar cells appears fragmented and can be
distinguished from the surface of epithelial cells
with microvilli (cf. Fig. 3.4). High magnification.
Cilia
Epithelial cell nuclei
Ciliated columnar epithelial cell

nucleus
Fig. 3.6 Stratified squamous epithelium

lining the vagina. The cells in surface layers are
squamous. Their nuclei appear elongated and the
cytoplasm sparse if they are sectioned across Basal epithelial cells
their narrowest dimension. Medium
magnification.
Lumen
Connective tissue
Connective tissue of dermis e.g. the liver and salivary glands, or rela-
tively small components of other struc-
tures, e.g. sweat glands of the skin.
There are two main functional types
of gland in the body:
■ exocrine glands that secrete their

products onto epithelial surfaces via
Basal epithelial cell nucleus
ducts
■ endocrine glands that secrete their
products (hormones) directly into
blood vessels.
Other secretory gland cells are present

Keratin layers in the body. Some, known as paracrine
glands, secrete factors into adjacent
regions, and unicellular glands such as
goblet cells secrete mucus onto the sur-
faces of the gastrointestinal and the res-
piratory tract (Fig. 3.5), for example.
Structurally, exocrine glands are of
two types: simple or compound. Sim-
Fig. 3.7 Keratinised, stratified, squamous epithelium of (thin) skin. The surface layers consist of ple glands are drained by a single,
the protein keratin. Cells just below the keratin are squamous. Cells in the basal layers are cuboidal. unbranched duct and the secretory cells
High magnification. forming the gland may be arranged as
straight or coiled tubules or in a spheri-
cal arrangement described as ‘acinar’
Connective tissue (Fig. 3.9A,B,C, respectively). Compound
glands have a branching duct system
that carries the secretion from gland
cells arranged as tubules or acini or a
combination of the two (Fig. 3.9D).
Exocrine glands synthesise their secre-
tory products and may store them in
membrane-bound structures. Secretions
are released from the cells by three
mechanisms:
■ merocrine secretion (Fig. 3.10A) involves

Elongated surface epithelial cell exocytosis (Chapter 2) of the product,
nucleus
which is typically protein based, and
constitutes the commonest
arrangement; the pancreas secretes
pancreatic enzymes by this
method
Transitional epithelial cell layers ■ apocrine secretion (Fig. 3.10B)
involves the release of membrane-
bound vesicles of secretory product
Lumen of urinary bladder
from the apex of the cell; this
arrangement is associated, mainly,
with lipid-based products as secreted
Fig. 3.8 Transitional epithelium lining the urinary bladder. The elongated shape of the surface by some sweat glands and the
epithelial cells in this layered epithelium indicates that the bladder was partially inflated when it was modified sweat glands that form the
fixed. High magnification. mammary glands
■ holocrine secretion (Fig. 3.10C)
involves the breakdown and release
of the contents of the whole cell;
amount it is stretched. In an empty Epithelial glands and membranes sebaceous glands of skin utilise
bladder, numerous epithelial cell layers this mode of secretion
are apparent. As the volume of urine Glands (Chapter 7).
in the bladder increases, the surface Epithelial gland cells are highly special-
epithelial cells become flattened and the ised and synthesise molecules for secre- Release of secretion from exocrine
number of layers of cells reduced, but, tion which may be protein, carbohydrate glands may be enhanced by nervous or
importantly, they continue to function or lipid based. Epithelial gland cells may hormonal stimuli acting on specialised
as a permeability barrier. form the major components of organs, cells known as myoepithelial cells. These
A C specialised epithelial cells surround the

secretory units (e.g. acini) and they
contain contractile proteins similar to
L those in muscle cells. Under nervous or
L
hormonal stimulation, the contractile
proteins in myoepithelial cells contract
and this applies pressure to the secre-
Basement
Nucleus Basement membrane tory units and helps to expel their
Duct membrane Duct secretions.
L
Membranes
Gland Cuboidal Epithelia form the surface layers of
epithelial cell
many membranes in the body, e.g.
serous membranes. Serous membranes
L Gland
B are very thin and their epithelia are
usually supported by sparse connective
tissue. Serous epithelial cells are usually
L cuboidal or squamous in shape and
form a simple epithelium, and they
Columnar secrete small amounts of fluid onto the
epithelial cell
surface of the membrane. Serous mem-
Nucleus Basement D branes have a variety of functions,
membrane
including covering organs and support-
Duct
ing the blood vessels and nerves passing
L L to them. Some serous membranes form
double-layered structures and the inner
visceral layer covering an organ is con-
tinuous with an outer (parietal) layer.
Basement
Duct membrane The two layers are continuous and
enclose a fluid-filled space. This arrange-
Gland ment of serous membranes is particu-
Cuboidal larly important for organs which move
Tubular
epithelial cell gland as they function, e.g. each lung is envel-
Basement membrane L oped by serous visceral and parietal
covering gland pleural membranes which enclose the
L
pleural cavity, the heart is enveloped by
pericardial membranes enclosing the
pericardial cavity, and parts of the gastro-
intestinal tract are enveloped by peri-
L Acinar toneal membranes which enclose the
gland
peritoneal cavity.
Fig. 3.9 Exocrine gland structure. (A) Simple tubular gland, (B) simple coiled tubular gland, (C)
simple acinar gland and (D) compound tubuloacinar gland. L, lumen. Recognising epithelia, other
primary tissues and organs
A B C If cells are lining or covering a surface it
will give the first clue as to whether
these are epithelial cells forming an epi-
thelium. To categorise the type of epi-
thelium, the number of layers of cells
and the shape of the cells must be deter-
mined and this is easier at higher mag-
nifications at which it is usually possible
to identify individual cell nuclei and
L L L their cytoplasm.
Connective tissue connects the base-
ment membranes of epithelia to other
structures and is thus readily recognised
if an epithelium has been identified.
Nucleus Secretion shed Nucleus Membrane and Nucleus Whole cell shed ■ In skin, the epithelium (epidermis)
from cytoplasm secretion shed with secretion is adjacent to the connective tissue
Fig. 3.10 Modes of secretion of exocrine glands. (A) Merocrine, (B) apocrine and (C) holocrine. L, lumen. of the dermis (Fig. 3.7).
■ In many tubes, e.g. of the digestive (Fig. smooth muscle (the muscularis Recognising organs relies on determin-
3.4), respiratory (Fig. 3.5), reproductive mucosae) lies deep to the mucosa of ing the primary tissues present and
(Fig. 3.6) and urinary (Fig. 3.8) systems, some of these tubes. their arrangement. The liver is a multi-
the epithelia and basement membranes ■ In blood vessels, the squamous functional organ in which epithelial
are adjacent to connective tissue epithelium (endothelium) is adjacent gland cells (hepatocytes) make up the
(known as the lamina propria). The to connective tissue (Fig. 3.2) and, in majority of the organ, the parenchyma
epithelium, basement membrane and some vessels, smooth muscle cells (Figs 3.3 and 3.11). Connective tissue
connective tissue lamina propria are also in close proximity. (known as stroma) is also present and it
together are described as a mucous provides support for, and connects, the
membrane (a mucosa). The epithelial Connective tissue occurs in regions hepatocytes, blood vessels and ducts in
surfaces of such structures are kept other than adjacent to epithelia; further the gland. Knowing the normal arrange-
moist by glandular secretions which details which aid recognising primary ment of the cells and tissues in an organ
are usually mucus or, in the case of the tissues, other than epithelia, are given in is essential before being able to decide
urinary tract, by urine. In addition, Chapters 4–6. whether abnormalities are present.
Lumen of blood vessel (vein)
Red blood cells
Endothelial cell nucleus
Hepatocyte nuclei
Connective tissue
Lumen of bile duct
Hepatocyte nuclei
Lumen of blood vessel (small artery)

Fig. 3.11 Liver. Epithelial gland cells (hepatocytes) form the major component (the parenchyma) of this organ. The hepatocytes, blood vessels and ducts
(draining bile) are supported and connected by connective tissue (stroma). A cuboidal epithelium lines the bile duct and endothelial cells line the blood
vessels. (Connective tissue is more readily distinguished with special stains; see Fig. 3.3.) Medium magnification.
Clinical notes
Repair Most types of epithelia are constantly being renewed under normal circumstances by mitosis of
undifferentiated stem cells in the epithelium, e.g. the life span of epithelial cells lining parts of the gut tube
is less than a week. Most damaged epithelia are able to repair themselves by the mitotic activity of their stem cells and
the rate at which this happens can readily be seen as cut skin repairs.
Tumours Many tumours in humans arise from epithelial cells undergoing abnormally high levels of cell
proliferation when new cells produced by mitosis exceed the rate at which cells are lost. If the new growth of
epithelial cells remains localised, it forms a benign tumour; if the new epithelial cells penetrate the basement
membrane, the growth is malignant and known as a carcinoma. It is only after this invasion through the basement
membrane has occurred that cancerous cells can spread to distant sites in the process known as metastasis. The extent
to which cancerous epithelial cells have penetrated their basement membrane and have changed their appearance is
used to judge the invasiveness of the tumour.
Summary
Epithelial tissue consists of epithelial cells attached to each other:
■ A simple epithelium has a single layer of epithelial cells and each is attached to the basement membrane.
■ A compound (stratified) epithelium has several layers of epithelial cells and only those in the basal layer are attached to the basement
membrane.
■ Epithelial cells line or cover structures in the body, form some membranes and form glands which secrete a variety of molecules:
■ exocrine glands discharge their secretions onto surfaces
■ endocrine glands discharge their secretions into blood vessels
■ paracrine and unicellular glands discharge their secretions in their local area.
Epithelial tissue has a variety of functions, reflected in its structure:
■ secretion
■ absorption
■ modulation of permeability to molecules
■ physical protection
■ detection of some sensations.
21
Chapter 4
Primary tissues 2: connective tissue
All connective tissues consist of cells ally, a cell with the suffix ‘blast’ indicates ■ macrophages, which are able to
derived from the mesoderm layer of a rapidly dividing cell. However, in the phagocytose and digest bacteria and
the embryo (see Mitchell B, Sharma R. case of the fibroblast, the term is usually cell debris. They are also able to
Embryology: An Illustrated Colour Text. reserved for the differentiated non-divid- phagocytose, but not digest, inert
Elsevier: 2004). In most types of con- ing cell, which might more appropriately substances, e.g. carbon particles. In
nective tissue the cells are widely be known as a fibrocyte.) addition, they aid the immune
spaced and separated by extracellular Several other types of cell occur in response to antigens (Chapter 8)
matrix which they have synthesised and connective tissues; some are restricted ■ white blood cells and plasma cells,
secreted. The types of cell and the com- to a particular type of connective tissue which may be in transit through the
ponents and consistency of the extra- and others to the functional state of the connective tissue or responding
cellular matrix relate to the location and tissue. locally as part of an immune
function of the particular type of con- They are: response (Chapter 8)
nective tissue. ■ adipocytes, which store fats (lipids)
Blood may be categorised as a con- ■ mast cells, which store granules in their cytoplasm (Fig. 4.1). The fats
nective tissue since its cells arise from containing specific molecules (e.g. may be metabolised and provide
mesoderm, but the extracellular matrix histamine). When released from energy and various metabolites
(plasma) is fluid (Chapter 8). Bone and mast cells these molecules modify when needed. Adipocytes also
cartilage are classified as connective the permeability of blood vessels as provide insulation, give shape to the
tissues and they have an extracellular part of an inflammatory reaction body and act as physical protection,
matrix that is relatively solid. In the case (Chapter 8) e.g. around the kidney.
of bone, the matrix is mineralised with
calcium salts which confer rigidity to the
bone and the ability to resist deforming
forces (Chapter 9).
Cell types in connective

tissue (excluding blood, Adipocyte cytoplasm
bone and cartilage)
The major cell type found in many con-
nective tissues is the fibroblast. In many Red blood cells in vessel
instances, fibroblasts are identified by
their densely stained, elongated nuclei
which do not appear to be associated
with much cytoplasm (Figs 4.1 and 4.2).
Fibroblasts secrete long, fibre-like protein
molecules (e.g. collagen and elastin) and
Fibroblast nucleus
many of the other large molecules in the
extracellular matrix.
Connective tissue fibres
If connective tissue is damaged, it may
be repaired by the ability of fibroblasts to
undergo mitosis and to synthesise new
matrix. If fibroblasts are actively secreting
Connective tissue septum
matrix proteins, their appearance is
changed: their nuclei are larger and rela-
tively palely stained and nucleoli are
apparent (Chapter 3, see Fig. 3.2). This
appearance is a result of the activity of
Fig. 4.1 Connective tissue, fibroblasts, fibres and adipocytes. Protein fibres, fibroblasts and
the DNA (and nucleolus) in the synthetic extracellular matrix form septa between clusters of white adipocytes. The adipocytes appear empty as
processes which produce new molecules lipid which filled the cytoplasm has been extracted during histological processing. Red blood cells are
for the extracellular matrix. (Convention- present in an endothelium-lined blood vessel. Medium magnification.
the body where deformation and refor- tissue and is subdivided into loose
Extracellular matrix of mation occurs. Elastin is present in skin (areolar) or dense categories
connective tissue and in the walls of arteries (Fig. 4.5). depending on the arrangement of
The extracellular matrix of connective Some arteries are distended as blood is the protein fibres
tissue comprises ground substance and pumped into them and then they recoil ■ reticular connective tissue has fine
protein fibres. It is the combination of (owing to the elastin fibres recoiling), fibres of reticulin which form a fine
these two elements that is important in thus ensuring the blood continues to supporting meshwork
determining the function of the connec- flow (Chapter 10). ■ adipose connective tissue in which
tive tissue. adipocytes (fat) cells are predominant.
Connective tissue types Connective tissue proper

Ground substance
Ground substance is a complex mixture Connective tissues may be divided into
Loose areolar connective tissue
of large molecules containing carbohy- three major types (excluding bone, car-
Loose areolar connective tissue occupies
drates and protein, and tissue fluid con- tilage and blood):
spaces that no other organs or tissues
taining water, salts, other small, soluble
■ connective tissue ‘proper’ is also occupy: it is packing material. It under-
molecules and dissolved gases. The
described as generalised connective lies the skin (the hypodermis), surrounds
tissue fluid component ensures gases
and nutrients move readily between
blood vessels and connective tissue cells
and other cells in the region. The large
molecules (glycoproteins, proteoglycans
and glycosoaminoglycans) bind the
components of the extracellular matrix
Keratin
together altering the viscosity of the gel-
like matrix and conferring on it different
properties. In addition, the matrix mol- Keratinised, stratified, squamous
ecules act as adhesion sites for various epithelium
transient cell types which may be
involved in immune responses.
Loose connective tissue fibres of

Protein fibres dermis
The protein fibres that are present in
extracellular matrix of connective tissues
are of two main types: collagen and Fibroblast nuclei
elastin. Collagen is characterised by
tensile strength and elastin by
elasticity.
Collagen
Collagen is synthesised by fibroblasts
and about 20 types have been identified
but only a few are common. Different
types of collagen are found in specific Dense collagen fibres of dermis
locations:
■ types I and II collagen are in bone and Fig. 4.2 Connective tissue, fibroblasts and fibres of skin. Fibroblasts are widely dispersed in the
skin (Fig. 4.2) and provide strength extracellular matrix of the dermis. In the deeper region, densely packed collagen fibres are
predominant. Medium magnification.
■ type II is in cartilage and provides
strength and allows some distortion
and recoil
■ type III (known as reticulin) Clinical notes
provides fine supporting fibres, e.g. Vitamin C deficiency Vitamin C is essential for the synthesis of
for liver cells (Fig. 4.3) normal collagen. Normally, collagen molecules are replaced several
■ type IV is in basement membranes months after they are formed by new collagen. If vitamin C is absent from
and provides firm attachments for the diet for prolonged periods the condition known as scurvy develops and
epithelial cells (Fig. 4.4). the new collagen that replaces the old is abnormal. Collagen attaches teeth
to the sockets in jaw bones; in extremely severe cases of scurvy, the teeth
drop out of the sockets because the new collagen is defective.
Elastin Marfan syndrome In this condition a genetic mutation results in the
Elastin molecules are also made and abnormal function of elastin fibres in the body. Many regions are affected
secreted by fibroblasts. The molecules but, in particular, the loss of the normal elastin component in the wall of
may be formed into sheets (laminae) or the aorta (the main blood vessel from the heart supplying the body) can be
distributed irregularly as fibres. Elastin serious as the wall may rupture; this is usually fatal.
molecules are predominantly in parts of
Primary tissues 2: connective tissue 23
port of gases and other molecules

between blood vessels and surrounding
cells and is a region where various cell
Parenchymal cell nuclei
types such as the cells of the immune
(hepatocytes) system (Chapter 8) can interact. Tran-
sient cell types such as white blood cells
may also be present in areolar tissue.
Loose connective tissue may respond to
trauma or infection by becoming oede-
matous and infiltrated by increased
numbers of white blood cells and other
immune-related cells (signs of
inflammation).
Loose connective tissue is character-
ised by abundant amounts of ground
Reticulin fibres
substance, and by fibroblasts which are
usually widely spaced and may appear
to have little or no cytoplasm. In histo-
logical sections ground substance may
appear as empty spaces since many
components may have been extracted
during the processing of the tissue. Also
present in loose connective tissue are
varying proportions of collagen and
elastin which appear as pink strands in
Fig. 4.3 Reticulin fibres in liver. Reticulin fibres appear as thin, dark brown strands. They provide routine H&E preparations (Figs 4.1 and
support for liver parenchymal epithelial cells (hepatocytes). Special stain. High magnification. 4.2). Some components of connective
tissue can be more readily revealed by
various special staining techniques (Figs
4.6 and 4.7).
Dense connective tissue

Basement membrane Dense connective tissue may be classi-
Lumen fied as regular or irregular with regard
to the arrangement of the fibres. The
former is arranged as bundles of simi-
larly oriented, densely packed collagen
Stratified epithelium fibres which resist tensile forces, such as
those applied to tendons (Fig. 4.8) and
ligaments. The predominant cell type is
the fibroblast. However, given the tight
packing of the collagen fibres, there is
relatively little space for extracellular
matrix or transient cells. Dense, irregu-
lar connective tissue also has densely
packed collagen fibres, but they are
arranged irregularly and resist tensile
forces from many directions. Again, the
predominant cell type is the fibroblast
and there is little space for extracellular
Basement membrane
material or transient cells. A typical site
for this type of connective tissue is the
deep region of the dermis of the skin
Fig. 4.4 Basement membrane supporting a stratified epithelium in the testis. This epithelium (Fig. 4.2).
lines tubules and is attached to a basement membrane which appears magenta as its content of
glycoproteins has been stained. Special stain. High magnification. Reticular connective tissue
The fine collagen fibres of reticulin act
as a delicate framework for the paren-
delicate organs and skeletal muscles, and urinary and reproductive tracts. It is also chymal cells of several organs, e.g. the
acts as filler around blood vessels and present in the delicate membranes attach- liver (Fig. 4.3) and endocrine glands (Fig.
nerves. Loose connective tissue physically ing organs or tubes to other structures, 4.7), where minimal impedance to the
connects many parts of the body, e.g. it e.g. the membranes of the gut (Fig. 4.6). transport of large molecules is impor-
binds together the constituents of the In addition to its ‘connective’ role, areolar tant. Reticulin also provides a support
walls of the gastrointestinal, respiratory, tissue also acts as a medium for the trans- network for immune cells in the
spleen, bone marrow and lymph nodes

(Chapter 8).
Adipose connective tissue Elastin

There are two types of adipose tissue:
white adipose and brown adipose tissue.
White adipose tissue is the most promi-
nent type in adults. It is also known as Smooth muscle cells
unilocular fat as each cell contains one
fat droplet which occupies most of the
cell. In brown fat, known as multilocular
fat, the constituent cells store the fat as
Elastin
multiple droplets. Both types of adipose
tissue have many blood vessels. White
adipose tissue contains connective tissue
fibres forming septa that break the
tissue up into lobules (Fig. 4.1). This type Endothelial cell nucleus
of adipose tissue is found under the skin
(subcutaneously), and it may be exten-
sive in particular regions of the body.
Brown fat is a reddish brown colour in
Elastin
life and its cells contain abundant mito-
chondria. The latter are related to its
Lumen of artery
principal function, which is to release
energy from the fat its cells contain.
Much of this energy is heat and it aids
temperature regulation in neonates.
Brown fat is found in particular loca-
tions in the body; it is most evident in
infants, although it is also found in the Fibroblasts and collagen
neck region of adults.
Fig. 4.5 Elastin in the wall of an artery. Elastin appears as a wavy line just deep to the endothelium
lining the lumen of this artery. The elastin has recoiled, hence the wavy line. The nuclei of the
endothelial cells bulge into the lumen. Layers of muscle cells, known as smooth muscle, form part of
the wall. Medium magnification.
Gland cell nuclei
Connective tissue
Fig. 4.6 A whole (not sectioned) thin

membrane. Some irregularly distributed protein Capsule (dense connective tissue)
fibres stain green and vary in thickness. Other
thin fibres (reticulin) stain dark brown. Nuclei of Fig. 4.7 Endocrine gland (adrenal). Connective tissue is stained blue. Dense connective tissue fibres
connective tissue and epithelial cells stain purple. surround the gland as a capsule and fine connective tissue fibres support the gland cells. Special stain.
Special stain. High magnification. High magnification.
Primary tissues 2: connective tissue 25
Fibroblast nuclei
Collagen fibres
Fibroblast nucleus
Fig. 4.8 Dense regular connective tissue of a tendon. The collagen fibres are distributed in
parallel arrays and nuclei of fibroblasts appear as dark dots in rows between the fibres. Medium
magnification.
Summary
Connective tissue:
■ consists of connective tissue cells in extracellular matrix (ECM)

■ the cells in many connective tissues are widely spaced
■ blood and bone and cartilage are specialised connective tissues.
Cells in connective tissue include:
■ fibroblasts which synthesise the protein fibres and other large molecules in the ECM
■ mast cells which synthesise, store and secrete molecules that affect the permeability of blood vessels
■ macrophages which phagocytose and digest cell debris and microorganisms, and aid immune responses
■ white blood cells which migrate through the ECM and may remain localised as part of the immune response
■ adipocytes which store lipids.
Extracellular matrix consists of:
■ ground substance containing

■ water, salts, dissolved gases and small molecules
■ large molecules, e.g. glycoproteins, proteoglycans and glycosoaminoglycans which affect the viscosity and function of the ECM
■ molecules to which cells involved in immune responses adhere
■ protein fibres
■ collagen types I and II provide strength, e.g. in skin
■ collagen type III (also known as reticulin) provides delicate meshworks which support other cells, e.g. in the liver
■ collagen type IV forms basement membranes which support many epithelial cells
■ elastin fibres which are able to stretch and recoil.
Categories of connective tissues (other than bone, cartilage and blood) are:
■ proper connective tissue

■ loose connective tissue connects structures
■ dense connective tissue has little ECM
■ reticulin connective tissue
■ adipose connective tissue.
26
Chapter 5
Primary tissues 3: muscle tissue
Muscle tissue consists of cells which are as the contractile myofilaments are glands; their contraction aids the
able to contract. The fundamental char- arranged in a repeating pattern in the expulsion of secretions
acteristic of each muscle cell is that it sarcoplasm and this is manifested as ■ myofibroblasts, which occur in many
has contractile proteins (mainly the transverse dark and light striations across regions of connective tissue; they aid
myofilaments actin and myosin) in its the length of the muscle cells (Figs 5.1A,B repair by secreting collagen and
cytoplasm. The force generated by the and 5.2). The precise arrangement of the undergoing contraction during scar
contraction of these proteins is transmit- contractile myofilaments are revealed formation
ted via connective tissue to other struc- only by using an electron microscope ■ pericytes, which surround capillaries;
tures. Contraction of muscles attached (see below). Although smooth muscle after injury they undergo mitosis
(by connective tissue) to bones will cells contain actin and myosin myofila- and replace damaged fibroblasts and
either move the bones at their joints or ments, they are not arranged in a regular smooth muscle cells.
stabilise the bones and joints by resist- pattern and smooth muscle cells do not
ing forces produced by other contract- display striations (Fig. 5.1C). Muscle cells and
ing muscles and by gravity. Contraction Other cell types with the ability to con- connective tissue
of muscles in the walls of various struc- tract have also been detected using tech-
Confusingly, muscle cells are also
tures in the body may increase the pres- niques which identify contractile proteins
referred to as muscle fibres, probably
sure within these structures and thus in their cytoplasm. These types include:
because some are long, thin structures
perform vital functions, e.g. heart muscle
■ myoepithelial cells, which surround which measure several centimetres in
contraction ensures blood flows away
acini and ducts of some exocrine length. (In contrast, connective tissue
from the heart and muscle in the walls
of gut tubes ensures the gut contents
pass from mouth to anus.
Nucleus
Specific terms have been introduced
A
to identify particular parts of muscle
cells (which are also known as muscle
fibres). The muscle cell membrane is LS TS
known as the sarcolemma, the cyto-
plasm as the sarcoplasm and the smooth
endoplasmic reticulum as the sarcoplas-
mic reticulum.
Cross striations Endomysium
(connective tissue)
Types of muscle tissue B
There are three types of muscle tissue
classified by location and the arrange- LS TS
ment of the contractile myofilaments in
the muscle cells:
■ skeletal muscle contraction is

Intercalated disc Nucleus Connective tissue
involved, mainly, in moving the
skeleton Endomysium
(connective tissue)
■ cardiac muscle contraction moves C
blood through the heart
■ smooth muscle in the walls of many
Nucleus
tubes and hollow organs (e.g. in
some blood vessels and the urinary LS TS
bladder) controls the flow of
substances along or out of such
structures.
Skeletal and cardiac muscle cells are Fig. 5.1 The longitudinal (LS) and transverse (TS) appearance of (A) skeletal, (B) cardiac and
referred to as striped or striated muscle (C) smooth muscle as revealed by light microscopy.
Primary tissues 3: muscle tissue 27
Skeletal muscle cells are multinucle-

ate, long and cylindrical in shape. They
form by fusion of several cells (myo-
blasts) during development in utero. The
nuclei of skeletal muscle cells are at the
periphery of the sarcoplasm (Figs 5.1A
Skeletal muscle cell nucleus and 5.2), a feature which allows them to
be distinguished from other types of
muscle cell. The contractile myofila-
ments (actin and myosin) within muscle
cells are arranged as bundles (myofibrils)
with their long axes along the length of
the cells (Fig. 5.3) and each cell contains
hundreds of myofibrils. The contractile
proteins in the myofibrils overlap each
other (Fig. 5.4A) and form a functional
unit (a sarcomere). Aligned in this way
the myofibrils refract light differently,
hence the striped appearance (Fig. 5.2).
The dark bands are known as A bands
and the I bands are light.
In histological sections of skeletal
muscle cells which have been sectioned
along their length, transverse striations,
reflecting the arrangement of the con-
tractile proteins, are apparent (Fig. 5.2).
If skeletal muscle cells are not sectioned
along their length the striations are not
apparent, but it is possible to recognise
Fig. 5.2 Skeletal muscle cells sectioned along their length. Light and dark transverse striations the type of muscle cell by the peripheral
occur along the length of muscle cells and are due to the regularity of the arrangement of the position of the nuclei (Figs 5.1A and 5.5).
myofibrils and myofilaments (actin and myosin) in the sarcoplasm. (The myofibrils and myofilaments Numerous blood capillaries (Fig. 5.6)
themselves are not revealed by light microscopy.) Special stain. Very high power. can be demonstrated in the connective
tissue layers around muscle cells. The
capillaries ensure a good blood supply,
fibres, although long and thin, are tissue fibres, is then transferred to other which provides the oxygen and nutri-
protein molecules, not cells.) structures such as bone e.g. the humerus ents necessary for muscle contraction.
The connective tissue associated with or soft tissue, e.g. the eyeball. Many skeletal muscles are anchored
muscle cells consists of three covering It is important to appreciate that when to bone by tendons (Chapter 4). The
layers (Figs 5.1 and 5.3). Each muscle cell muscles stop contracting they passively collagen fibres covering the muscle cells
is covered by, and bound to, fine connec- relax and the contractile proteins resume are continuous with the collagen of the
tive tissue fibres which form an external their original position but this does not tendon. In turn, bundles of collagen,
(basal) lamina known as an endomy- exert a force. Muscles can only contract known as Sharpey’s fibres, pass into the
sium. Several muscle cells are held (pull), never push! bone and anchor the tendon. Tendons
together as bundles by connective tissue take on a variety of forms, such that the
fibres known as the perimysium. The Skeletal muscle attachment may be focal or broad. In
connective tissue covering a muscle As its name suggests this type of muscle some muscles the connective tissue sur-
itself, e.g. the biceps brachii, is called the is associated with the skeletal system, rounding the muscle cells attaches to a
epimysium; this layer is also known as and it is responsible for movements of collagen (fascial) layer (Fig. 5.7), rather
deep fascia. bones and joints. Skeletal muscle is than to bone.
Contraction of a muscle, such as also known as voluntary muscle as its Variation occurs in the size of muscle
biceps brachii, involves the contractile contraction is usually under conscious cells, the number of mitochondria they
proteins in individual muscle cells control via its nerve supply. Skeletal contain and the enzymes present, as
moving and shortening their overall muscle gives characteristic form to the well as their content of myoglobin.
length. This movement generates a force body’s contour (along with adipose Myoglobin, an oxygen-carrying protein,
of contraction and it is transmitted to tissue). Although gross anatomy is resembles haemoglobin and gives
the sarcolemma and the external lamina. beyond the scope of this book, it is muscle a reddish colour. Such red
The laminae around adjacent muscle important to appreciate that the attach- muscle cells are predominant in muscles
cells are connected to each other and to ment sites of a skeletal muscle to the in which sustained contraction is
the other layers of connective tissue. In skeleton, and the position of the muscle required, e.g. to maintain posture. In
this way the force of muscle cell contrac- in relation to a joint, will determine the contrast, in muscles where fast contrac-
tion is transmitted to all the connective line of pull of the muscle and the type tion and spurts of activity occur
tissue layers. Such contractile forces of movement that occurs at the joint as myoglobin is sparse and the muscles
from muscle cells, applied to connective the muscle contracts. appear whitish to the naked eye.
Cross striations Myofilaments Actin

myofilaments
Myofibril
Relaxed
Muscle cell
Sarcomere
Contracted
Muscle cell Nucleus B
Endomysium
Myosin
myofilament
Epimysium
Fig. 5.4 The arrangement of actin and
myosin myofilaments in a sarcomere in the
relaxed (A) and the contracted (B) state.
Perimysium
Ultrastructure of skeletal muscle and

contraction
Contractile proteins occupy much of the
sarcoplasm of muscle cells, and the
thick myosin and thin actin myofila-
Part of muscle ments can be identified in cells sectioned
(e.g. biceps brachii)
longitudinally and transversely (Figs 5.8
and 5.9 respectively). Numerous mito-
chondria (Fig. 5.9) are present in muscle
cells and myoglobin and glycogen may
also be present; all aid in providing
Fig. 5.3 The three connective tissue layers covering muscle cells in part of a muscle. energy for contraction. An extensive
Myofilaments in one myofibril of a muscle cell are shown. membranous meshwork connecting
the sarcolemma and the sarcoplasmic
reticulum (the t tubule system) is
present (Fig. 5.9). This meshwork has a
role in moving calcium ions into the
sarcoplasm, which is a process that is an
essential trigger for muscle contraction.
The functional unit of the skeletal
Connective tissue
muscle cell is known as a sarcomere
(Fig. 5.4) and it consists of thin (actin)
and thick (myosin) myofilaments and
other proteins which anchor them in
Skeletal muscle sarcoplasm
parallel arrays and to the sarcolemma.
Contraction involves the parallel actin
and myosin proteins sliding along each
other (Fig. 5.4), thus shortening the cell
Skeletal muscle cell (with 2 nuclei) overall. This is known as the sliding fila-
ment mechanism of contraction and is
Skeletal muscle cell nucleus an energy-dependent process.
Cardiac muscle
Connective tissue This type of muscle, like skeletal muscle,
appears striated (Figs 5.1B and 5.10)
Space (artefact)
owing to the arrangement of the actin
and myosin proteins in the sarcoplasm.
Unlike skeletal muscle, cardiac muscle
contraction is not under conscious
control. Cardiac muscle cells are cylin-
Fig. 5.5 Skeletal muscle cells sectioned across their length. Connective tissue surrounds each drical and much shorter than skeletal
muscle cell and groups of muscle cells. Some spaces are artefacts due to shrinkage during preparation muscle cells. Each cardiac muscle cell
of the section. High magnification. has a single, centrally placed nucleus
Fig. 5.6 Skeletal muscle cells (yellow) sectioned along their length showing blood vessels
(red). A rich network of small blood vessels passes, in connective tissue, along the length of the
muscle cells. (No details of the muscle cell structure or connective tissue are displayed.) Special stain.
Medium magnification.
Dense connective tissue (fascia)
Fig. 5.7 Skeletal muscle cells (yellow) from tongue. The skeletal muscle cells are sectioned along
their length and display their peripheral nuclei. Connective tissue (stained red) surrounds each muscle
cell and provides a dense fascial layer of collagen to which the muscle cells are attached. Forces from
contraction of the muscle cells are transferred to the connective tissue and change the shape of the
tongue. Special stain. Low magnification.
and some cells branch (Fig. 5.1B). Spe-

cialised cell junctions (Chapter 2) link
cardiac muscle cells end to end and
these regions, called intercalated discs,
are visible in histological sections (Fig.
5.10). Desmosomes and zonulae adher-
Myofibril
ens anchor the muscle cells together at
intercalated discs. In addition, there are
gap junctions at these discs which
ensure the excitation stimulating con-
traction spreads rapidly between muscle
cells and results in their synchronised
contraction. The mechanism of contrac-
tion is similar to that of skeletal muscle.
The connective tissue associated with
cardiac muscle (Fig. 5.10) is arranged in
layers similar to those of skeletal muscle
and it transmits the forces of the muscle
contraction. The arrangement of con-
nective tissue fibres forms a fibrous
‘skeleton’ for the heart. This arrange-
ment helps to ensure that the contrac-
tion of heart muscle cells constricts the
chambers of the heart in synchrony and
Fig. 5.8 Electron micrograph of part of the sarcoplasm of a skeletal muscle cell sectioned it also anchors the heart valves and aids
along its length. The length of a sarcomere in a myofibril is indicated by arrows. Thick (myosin) and their function (Chapter 10).
thin (actin) myofilaments can be seen in parallel linear arrays in the sarcomere (and in other regions of
the myofibrils shown) as thick (myosin) and thinner (actin) lines. High magnification.
Smooth muscle
Smooth muscle cells are fusiform in
shape and tapered at each end with a
centrally placed nucleus (Fig. 5.1C).
Smooth muscle cells are usually grouped
together and form sheets or bundles,
and their appearance in histological sec-
tions depends on the angle at which
they are sectioned (Figs 5.1C and 5.11)
and their state of contraction (Fig. 5.12).
Contraction of smooth muscle cells is
not under conscious control and they
Sarcoplasmic reticulum are described as involuntary muscle
cells. The contractile proteins in smooth
muscle cells are arranged irregularly
and some are linked with adherens-type
junctions at intervals on the inner
surface of the cell membrane. Each
muscle cell is attached to an external
lamina of connective tissue (endomy-
sium) (Fig. 5.1C) and muscle cells are
bundled together by layers of connective
tissue (Fig. 5.11). Between some muscle
cells the external lamina is incomplete
and gap junctions link adjacent smooth
muscle cells. The presence of gap junc-
tions aids the spread of the excitatory
Mitochondrion stimulus for contraction and helps
groups of cells to contract as a single
unit. When smooth muscle cells con-
tract they take on a corkscrew-like shape,
Myofilaments in a myofibril which may be apparent as a change in
shape of the nucleus (Fig. 5.12), and the
Fig. 5.9 Electron micrograph of part of the sarcoplasm of a skeletal muscle cell sectioned
across its length. Myosin (thick) and actin (thin) myofilaments can be seen sectioned across their force is transmitted via their external
length in several myofibrils as dark dots (myosin) and smaller, paler dots (actin). Very high laminae to other surrounding connec-
magnification. tive tissue.
Muscle contraction and

nerve supply
Skeletal muscle contraction is dependent
on its nerve supply. Indeed, if the nerves
supplying skeletal muscles are severed
the muscle cells do not contract and
they waste away (atrophy). Cardiac and
smooth muscle cells have an intrinsic
ability to contract in the absence of nerve
supply. However, they are supplied by
Intercalated discs
nerves which control their activity but
they are not normally under conscious
control. Further details of the nerve
supply to muscles is given in Chapter 6.
Connective tissue
Clinical note
Muscle hypertrophy,
hyperplasia and
repair Adult skeletal muscle is
able to undergo hypertrophy:
the muscle cells become larger
Cardiac muscle cell nuclei as they respond to exercise by
forming more contractile proteins.
Although skeletal muscle cells are
not able to undergo mitosis, if
very minor damage occurs some
repair may occur. This is due to
Fig. 5.10 Cardiac muscle cells sectioned along their length and associated connective tissue a minor population of
(blue/green). Special stain. Medium magnification. undifferentiated cells (known as
satellite cells) in skeletal muscle
which can differentiate into
skeletal muscle cells.
Cardiac muscle cells can
also increase in volume by
hypertrophy, and this can occur
in response to high blood
Smooth muscle cells pressure (hypertension). In
contrast to skeletal muscle, there
are no stem cells in cardiac
muscle and so there is no
replacement of dead cardiac
muscle cells. After a heart attack
Lumen of blood vessel
(myocardial infarction), cardiac
muscle cells die because of loss of
their blood supply and they are
not replaced. Fibroblasts in the
Connective tissue
connective tissue of the heart
proliferate and secrete collagen
and a fibrous scar takes the place
of the dead muscle cells. The scar
Smooth muscle cells may alter the contraction of the
normal heart muscle with
harmful consequences.
Smooth muscle cells can
undergo hypertrophy (increase
in cell size) and hyperplasia
Fig. 5.11 Bundles of smooth muscle cells sectioned along their length (upper region) and
(increase in cell number). These
across their length (lower region). Many of the smooth muscle cells sectioned across their length
do not appear to have nuclei as the section has passed though a region of cytoplasm away from the processes are particularly
nucleus. The nucleus and cytoplasm of smooth muscle cells sectioned longitudinally appear elongated important in ensuring uterine
as the long axis of each cell is in the plane of the section. Connective tissue (green) surrounds and muscle is able to function during
separates the muscle cells and bundles, and two small blood vessels. Special stain. Medium pregnancy and childbirth.
magnification.
Space (artefact)
Smooth muscle cell nucleus
Connective tissue
Smooth muscle cell nuclei
Smooth muscle cell nucleus
Fig. 5.12 Smooth muscle cells sectioned along their length. Some nuclei of smooth muscle cells
appear normal (fusiform) in shape; others appear kinked, which is typical of smooth muscle cells fixed
in a state of contraction. Some spaces are artefacts due to shrinkage during processing. Other spaces
are the lumina of blood vessels lined by endothelial cells. High magnification.
Summary
Muscle tissue
■ Muscle tissue comprises three main types of muscle cell:
■ skeletal, cardiac and smooth.
■ Myoepithelial cells, myofibroblasts and pericytes also have the ability to contract.
■ Intracytoplasmic proteins (mainly the myofilaments actin and myosin) in muscle cells (and the above cell types) are responsible for
contraction.
■ Connective tissue adjacent to muscle cells transmits the force of contraction to other structures.
Skeletal muscle
■ Cells are multinucleate and nuclei are adjacent to the sarcolemma (muscle cell membrane).
■ Cells are long, cylindrical and display transverse striations reflecting the linear arrangement of the myofilaments in the sarcoplasm (cytoplasm).
■ Contraction moves bones at joints and/or stabilises joints.
■ Contraction is (mostly) under conscious control via the nerve supply.
Cardiac muscle
■ Cells are cylindrical, relatively short, and have a single, centrally placed nucleus.
■ Cells display transverse striations corresponding to the linear arrangement of myofilaments.
■ Cells have intercalated discs showing the end-to-end connection of these cells.
■ Contraction is under the (unconscious) control of nerves.
■ Contractions, transmitted to connective tissue in the heart, move blood through the heart in a synchronised manner.
Smooth muscle
■ Cells are fusiform in shape and a nucleus is in the centre of each cell.
■ Cells have few randomly arranged myofilaments.
■ Cells occur in bundles or layers around many tubes.
■ Contraction is under (unconscious) control of nerves.
33
Chapter 6
Primary tissues 4: nerve tissue
Nerve tissue comprises neurons (nerve ■ Variation in shape. Neurons are

cells) and a range of cells that support
Neurons classified as multipolar (Fig. 6.1),
the neurons, e.g. glial and satellite cells. Neurons are derived from the ectoderm bipolar or pseudounipolar (Fig. 6.5).
Nerve tissue is involved in carrying germ layer of the embryo (see Mitchell The polarity is related to the
rapid, specific communications between B, Sharma R. Embryology: An Illustrated number of cytoplasmic processes
various parts of the body. Neurons Colour Text. Elsevier: 2004). Most projecting from the perikaryon.
gather information, process it and trans- neurons have a large mass of cytoplasm Many neurons are multipolar and,
mit signals to other neurons or other and large nucleus forming the body typically, one axon and many
cell types (e.g. muscle and gland cells). of the cell (the perikaryon) and a varia- dendrites extend from the
The transmitted signals affect the func- ble number of cytoplasmic processes perikaryon (Fig. 6.1). Some neurons
tion of the recipient cells. (Fig. 6.1). Perikarya may measure up in the brain and ventral regions
to 150 μm in diameter, which is about (horns) of the spinal cord are
20 times larger than a red blood cell. multipolar. Bipolar neurons are
Nerve tissue and the present in organs of the special
The cytoplasmic processes are of
nervous system senses (e.g. the eye) and they have
two forms, dendrites and axons. Most
The nervous system has two structural neurons have several short dendrites two cytoplasmic processes, one an
components. Nerve tissue located in the that receive signals which they then
brain and spinal cord is the major com- pass to their own cell body. In general,
ponent of the central nervous system each neuron has a long, single axon Cell body
(perikaryon)
(CNS). Other primary tissues are present which takes signals away from the Dendrites
in the CNS though they are sparse, e.g. perikaryon either to other neurons or
connective tissue provides some support. to other cell types, e.g. muscle cells. Nucleus
The peripheral nervous system (PNS) Axons may be up to about a metre in
comprises nerve tissue which is not in length in humans, i.e. the length from Dendrite
the CNS, e.g. cranial and spinal nerves the lower regions of the spinal cord to
and their branches, and autonomic the foot.
Nucleolus
nerves (see below). Connective tissue In routine H&E-stained sections, neu-
also has a supporting role in the PNS. ronal nuclei have large, palely stained Cytoplasm Myelin sheath
The nervous system has two func- areas (Fig. 6.2). Such areas represent
tional components, somatic and auto- uncoiled euchromatin, the hallmark of Node of Ranvier
nomic. The somatic nervous system DNA transcription and a prerequisite
involves the detection of sensations and for protein synthesis. The cytoplasm in
the control of skeletal muscle contrac- neuronal cell bodies often appears gran-
tion. Some sensations are not con- ular, especially if special stains have
sciously perceived, such as a change in been used (Fig. 6.3). The granules are
tension in a tendon, though the change referred to as Nissl granules and they
detected can cause a response, such as are due to large accumulations of
Interruption
contraction of skeletal muscle(s). The rough endoplasmic reticulum (RER), indicating
functions of the autonomic nervous which are involved in the synthesis of variable length
system (ANS) involve the control of con- various proteins. Some of these proteins
traction of smooth and cardiac muscle provide the structural tubules and fila-
cells and the secretory activity of some ments in axons and dendrites. Others
gland cells. The ANS, in general, is not are enzymes involved in producing mol-
Axon terminal
under conscious control. However, an ecules which aid the transmission of
important exception is that the auto- signals.
nomic nerves involved in controlling the Neurons vary in shape and size, and Skeletal muscle
cell
smooth muscle cells in the wall of the according to function and location. The
Fig. 6.1 The structure of a typical multipolar
urinary bladder are normally under complexity of their cytoplasmic proc- neuron (a motor neuron with its axon
conscious control by the age of 2–3 esses is vast and revealed by special ensheathed in myelin). Arrows indicate the
years. stains (Fig. 6.4). direction of travel of the nerve impulse.
axon and one a dendrite.

Pseudounipolar neurons possess one
process, though it bifurcates and one
branch receives signals and the other
Axons and dendrites
branch transmits them away from
the cell body. Examples of
pseudounipolar neurons are those
that transmit sensory information
from the skin.
■ Variation in function. All neurons
respond to stimuli by transmitting
Nucleolus of neuronal cell nucleus
signals along their axons, away from
Support cell nucleus their cell body. The signals are in
Neuronal cytoplasm the form of nerve (electrical)
impulses which move rapidly along
the axon. As the nerve impulses
Fig. 6.2 Ganglion. A neuronal cell body (perikaryon) with palely stained nucleus and densely stained reach the terminal part of the axon
nucleolus and extensive cytoplasm. The cytoplasm of axons and dendrites cannot be distinguished: the signal is passed on by various
both appear as pink strands. High magnification. molecules (neurotransmitters)
released from the axon. The
neurotransmitters stimulate a
response in the target cell. If the
target cell is another neuron the
signal continues as a nerve impulse.
Connective tissue If the target cell is a muscle cell, the
neurotransmitter stimulates the
muscle cell membrane and this
results in the muscle cell undergoing
contraction.
The rate at which nerve impulses
are transmitted along axons varies.
In general, the wider the diameter of
an axon, the faster the nerve impulse
Neuronal nucleus (with nucleolus) travels. The speed of transmission of
nerve impulses is also higher in
axons that are sheathed in myelin
(Fig. 6.1). Myelin is a lipid bilayer
Nuclei of neurons arranged as concentric, multiple
(each line ends on a nucleolus) layers around some axons (Figs 6.6A,
6.7 and 6.8). The layers are formed
from the cell membranes of
Schwann cells in the PNS and, in the
CNS, from the cell membranes of
certain glial cells (oligodendrocytes).
Neuronal cytoplasm
In places, the myelin sheaths around
axons are not layered and these
regions are described as nodes of
Ranvier (Figs 6.1 and 6.9). The nodes
are the interface between two
adjacent myelin-producing cells and
they are important in ensuring a
Axons and dendrites
relatively rapid rate of transmission
of the nerve impulse. Other axons
are not ensheathed in myelin, but
Fig. 6.3 Ganglion. Some neuronal cell bodies appear to lack a nucleus; this is because a section 5 μm several axons are indented into the
thick through neuronal cell bodies which may be 150 μm in diameter could miss the nucleus. cytoplasm of one myelin-producing
Connective tissue (blue) surrounds and is within the ganglion. Special stain. Medium magnification. Schwann cell (Fig. 6.6B).
Transmission of impulses along
these non-myelinated axons is
relatively slow.
■ Variation in location. Afferent
neurons carry sensory signals to the
CNS and efferent neurons carry
signals away from the CNS to
Primary tissues 4: nerve tissue 35
Neuronal cytoplasmic process
Dendrite
Neuronal cell body
Neuronal
cell body
Nucleus
Nucleolus
Axon
Neuronal cytoplasmic process
Neuronal cell body
A B
Fig. 6.5 The structure of (A) a
pseudounipolar and (B) a bipolar neuron.
Arrows indicate the direction of travel of the
nerve impulse.
Fig. 6.4 Neurons in brain. Perikarya and numerous cytoplasmic processes show some of the
variation and complexity of their connections. Special stain. Medium magnification.
Layers of myelin Axons
Mitochondria
Schwann cell
cytoplasm
Schwann cell
nucleus
A B
Fig. 6.6 The relationship of a Schwann cell and myelin in a transverse section of (A) a
myelinated axon and (B) non-myelinated axons.
Fig. 6.7 Peripheral nerve (with cytoplasmic
processes of many neurons) sectioned across
its length. The lipids in Schwann cell
various cells, e.g. muscle and gland afferent neurons have specialised
membranes which form myelin sheaths are
cells. Afferent nerves enter the spinal structures known as sensory shown as black circles. The axons which occupy
cord by dorsal roots and efferent receptors (Fig. 6.11) at the peripheral the centre of the circles are not stained. Special
nerves leave by ventral roots (Fig. end of a cytoplasmic process; others stain. High magnification.
6.10). Some afferent neurons end as ‘free nerve endings’. Sensory
communicate directly in the CNS receptors in, for example, the skin
with efferent neurons and form a detect sensations, and nerve perceived consciously, e.g. changes in
two-neuron reflex arc (pathway) (Fig. impulses are transmitted to the blood pressure, but the body
6.10A). Others transmit information CNS. Sensory receptors in skin can responds to the changes detected.
to interneurons in the spinal cord provide impulses that are perceived Highly specialised sensory neurons
which in turn communicate with as pain, touch (differentiating type are present in the organs involved in
efferent neurons in a three-neuron and pressure) and temperature. sight, hearing, smell and taste; for
arc (Fig. 6.10B). In both types of Signals from sensory receptors in information about these, a more
reflex arc other neurons transmit some organs may be perceived as detailed histology book should be
impulses to the brain. changes in pressure or amount of consulted.
Afferent (sensory) neurons provide stretch. Other sensory receptors Efferent neurons transmit
a variety of information. Some convey information which is not impulses away from the CNS and
affect the function of other neurons

and other cells, e.g. gland and
muscle cells (efferent neurons which
stimulate muscle contraction are
known as motor neurons (Fig. 6.1)).
There are two categories of efferent
neuron:
■ Somatic efferent neurons. These

stimulate skeletal muscle
Axonal cytoplasm contraction and may involve a
(with tubules) series of nerve impulses
originating in the brain after
conscious thought. Skeletal muscle
Myelin sheath contraction may also occur as a
reflex response, e.g. to a painful
stimulus. The sensory information
passes in a reflex arc through the
spinal cord (Fig. 6.10) and directly
(or via an interneuron) to one or
more efferent motor neurons
which stimulate muscle
contraction. This reflex pathway
does not involve the brain but
neurons relay the pain sensations
Schwann cell nucleus (part of)
rapidly to the brain and then the
Fig. 6.8 Electron micrograph of a transverse section of an axon and surrounding myelin
pain is perceived.
sheath. Very high magnification.
■ Autonomic efferent neurons. These
control smooth muscle contraction,
e.g. smooth muscle in the walls of
blood vessels and the walls of the
digestive, respiratory, reproductive
and urinary tracts. Autonomic
efferent nerves also control the
contraction of cardiac muscle cells
and gland cell secretion, e.g. by
salivary and sweat glands.
Synapses
Synapses are specialised cell junctions
Node of Ranvier between neurons or between neurons
and other cell types, e.g. muscle cells.
The commonest form of synapse is the
axo-dendritic synapse formed between
the axon of a neuron and the dendrite(s)
of another neuron.
All synapses have similar characteris-
tics (Fig. 6.12). In axo-dendritic synapses
the membrane of the terminal part of
the axon of the presynaptic cell lies in
close apposition to the membrane of a
Myelin sheaths dendrite of the postsynaptic cell. The
space between the two cells is known as
the synaptic cleft. The neuron transmit-
ting the nerve impulse to a synapse has
Node of Ranvier a presynaptic axonal swelling in which
numerous cellular organelles and syn-
aptic vesicles are present. The synaptic
vesicles are small membrane-bound
structures containing neurotransmitter
molecules. The morphology of synaptic
Fig. 6.9 Cytoplasmic processes (axons) of neurons sectioned along their length. Special stain. vesicles is related to their content. The
Very high magnification. main neurotransmitters include acetyl-
Afferent neuronal cell body White Pseudounipolar afferent choline and catecholamines such as
in spinal ganglion matter neuronal cell body noradrenaline and dopamine.
Dorsal root Cytoplasmic
process of The arrival of a nerve (electrical) im-
afferent neuron pulse at a synapse triggers the release of
(from sensory neurotransmitter molecules into the
receptor)
synaptic cleft. The neurotransmitters
bind to the membrane of the postsynap-
Axon of tic cell and, if it is another nerve cell, a
interneuron
nerve (electrical) impulse is produced
Spinal nerve and transmitted by the postsynaptic
neuron.
Synapses between axons and muscle
cells are known as motor end plates (Fig.
Axon of efferent Ventral Grey Axon of efferent neuron 6.13). Each axon usually branches at its
neuron root matter to muscle or gland peripheral end and forms synapses with
A B several muscle cells. The presynaptic
Fig. 6.10 The spinal cord (sectioned transversely) showing grey and white matter. Arrows axonal membrane abuts the highly
show the routes taken by sensory (afferent) and motor (efferent) cytoplasmic processes of neurons in folded postsynaptic muscle cell mem-
forming (A) a two-neuron and (B) a three-neuron reflex arc. brane. The two membranes are sepa-
rated by the synaptic cleft. The release
of neurotransmitters triggers changes
in the ionic permeability of the mem-
brane of the muscle cells, which
results in contraction. The motor neuron
and the muscle cell (or cells) with which
it synapses is described as a motor
unit.
Ganglia and nuclei

Nerve (sectioned transversely)
Ganglia are defined as collections of neur-
onal perikarya (cell bodies) not in the
Red blood cells in vessel CNS. The equivalent aggregations of
neuronal perikarya in the CNS are
known as nuclei. In addition to neuronal
cell bodies, ganglia also contain support-
ing (satellite) cells and parts of the cyto-
Nerve (sectioned longitudinally) plasmic processes (axons and dendrites)
of neurons (Figs 6.3 and 6.14). The satel-
lite cells surround and support the peri-
karya in ganglia by providing electrical
insulation and ensuring that nutrients
reach the neuronal perikarya. Connective
tissue surrounds each ganglion and a
sparse network of connective tissue is
Connective tissue present within each (Fig. 6.3).
There are two types of ganglion:
■ Spinal ganglia are attached to spinal

Sensory receptor nerves (Fig. 6.10) and located in
intervertebral foramina. They are
characterised by collections of
closely packed sensory, pseudo-
Fig. 6.11 A sensory receptor (Pacinian corpuscle) and peripheral nerves (sectioned across
unipolar, neuronal perikarya. They
their length and along their length). Medium magnification.
receive and transmit signals about
sensations through their single
cytoplasmic process. Each cell body
is surrounded by a layer of satellite
cells (Fig. 6.14).
■ Autonomic ganglia are part of the
ANS and occupy sites near to the
spinal cord (in pre- and
paravertebral ganglia) and in the
walls of, or close to, some viscera.

The neuronal cell bodies in
Nucleus of
presynaptic cell autonomic ganglia are multipolar
and receive signals, via synapses,
from axons of preganglionic
Indicates axon may neurons. They transmit the signals
be several centimetres long away from ganglia via their axons.
Autonomic ganglia are classified
Axon into two functional types,
Neurofilaments sympathetic and parasympathetic.
and microtubules
■ Sympathetic ganglia. The neurons
in these ganglia are involved in
the body’s alarm responses (fright,
fight and flight) and are in the
Axon terminal
sympathetic chain of paravertebral
Mitochondrion ganglia and in prevertebral
Synaptic vesicle
ganglia.
Nucleus ■ Parasympathetic ganglia.
Synaptic cleft Parasympathetic neurons are
involved in the ‘rest and digest’
Dendrite of postsynaptic activities of the body. They are
cell with receptors for
neurotransmitters similar in structure to sympathetic
Postsynaptic ganglia but are typically found in
Nucleolus cell body the walls of, or near to, the organs
Axon they affect (Fig. 6.15) and the
number of perikarya present is
Fig. 6.12 The structure of an axo-dendritic synapse. Arrows (large black) indicate the direction of often quite small.
travel of the nerve impulses.
Glial cells
Glial cells are present in the CNS and
they are more numerous than the
neurons. They function in maintenance,
support and repair. There are three
types: astrocytes, oligodendrocytes and
Motor end plate
microglial cells.
■ Astrocytes. Each astrocyte has a

small cell body with numerous,
radiating, small cytoplasmic
processes like stars, hence their
name. They act in two ways. Firstly,
they have cytoplasmic processes that
are wrapped around blood vessels;
Motor end plate this is an important structural and
functional relationship forming the
blood–brain barrier. This barrier
prevents the passage of molecules
Muscle cells (unstained) larger than about 500 daltons
between blood and brain. Secondly,
they repair damaged tissue, a
process known as gliosis. The latter
Axons
is the equivalent of repair by
fibroblasts in the rest of the body.
■ Oligodendrocytes. These cells
Fig. 6.13 Motor end plates. Special stain. Medium magnification. produce myelin which ensheaths
some axons in the CNS.
■ Microglia. These are small cells and
they are the only nerve tissue cells
which originate from mesoderm. In
response to inflammation, they
undergo phagocytosis and aid repair;
in this they resemble macrophages
(Chapters 4 and 8).
the spinal cord it is the central region

(Fig. 6.10). Neuronal cell bodies are pre-
dominant in grey matter, and axons,
particularly myelinated axons, are prom-
inent in white matter. To the unaided
eye, white matter appears white; it is the
lipid content of myelin that gives this
Neuronal cytoplasm
appearance. In histological sections the
Neuronal nucleus regions of grey and white matter can be
clearly revealed (Fig. 6.16).
Satellite cell nucleus
Neuronal cytoplasm
Peripheral nerves
Peripheral nerves pass between the CNS
and the rest of the body. The peripheral
nerves attached to the brain are known
as cranial nerves and those attached to
the spinal cord as spinal nerves. Periph-
Axon eral nerves may be up to 2 cm in width
and contain the cytoplasmic processes
(axons and dendrites) of a very large
number of neurons. Numerous
Fig. 6.14 Ganglion. Neuronal perikarya are surrounded by satellite cells. Many neuronal cytoplasmic ensheathing Schwann cells and connec-
processes are sectioned across their length. Lipid has been extracted from myelinated axons during tive tissue are also present. Peripheral
processing and this appears as small spaces around some of the axons. Medium magnification. nerves become smaller as they branch
and pass around the body to the sites
where the neuronal cell processes they
contain initiate or receive signals. Their
appearance in histological sections varies
depending on the angle at which they
are sectioned (Fig. 6.11). Individual cyto-
plasmic processes are difficult to dis-
tinguish in peripheral nerves but the
Neuronal cell nuclei nuclei of Schwann cells and supporting
connective tissue cells can be seen,
although not always distinguished
(Fig. 6.11).
Peripheral nerves contain layers of
connective tissue (Fig. 6.17). The connec-
tive tissue wraps around axons at three
Smooth muscle cell nuclei levels of organisation. Endoneurium
surrounds individual axons. Groups of
axons, with their coverings of endo-
neurium, are bundled together and
surrounded by perineurium. The
perineurium also packs the space
between adjacent bundles of axons.
Several bundles of axons within their
Smooth muscle cell layers investments of endoneurium and
perineurium are surrounded by the con-
Fig. 6.15 Parasympathetic ganglion in the wall of the small intestine. These ganglion cells lie
between two layers of smooth muscle. Connective tissue is stained blue. Special stain. Medium nective tissue of the epineurium.
magnification. Most peripheral nerves contain neur-
onal cell processes which transmit
impulses to the CNS and other cell proc-
esses which transmit impulses away
from the CNS, respectively processes
Illustrated Colour Text, 3rd edn. Elsevier: from afferent and efferent neurons. All
Brain and spinal cord 2005). Two principal areas are described peripheral nerves also carry cytoplasmic
The arrangement of neurons in brain in brain and spinal cord as white and processes from sympathetic nerves,
and spinal cord is complex (see Cross- grey matter. In the brain, grey matter whereas some of those in the head and
man AR, Neary D. Neuroanatomy: An forms the peripheral region, whereas in trunk also carry parasympathetic nerves.
Clinical notes
Blood–brain
White matter barrier The blood–
brain barrier presents a physical
barrier to molecules over 500
Neuronal cytoplasmic processes daltons in size. If the barrier
breaks down, the brain may swell.
This condition, known as cerebral
oedema, may also develop in
response to a lesion in the brain,
e.g. a tumour or an abscess, or
after trauma, or after a stroke
resulting in ischaemic brain
damage.
Tumours of nervous
tissue Such tumours are not
usually derived from neurons.
Neurons do not divide, thus we
Neuronal cell bodies are born with the maximal
number of neurons and many die
as life progresses. Tumours of
nerve tissue are mainly of the
glial cell lineage. Of these,
astrocytomas are the commonest.
The most severe form is highly
malignant and patients have a
Grey matter
very poor prognosis.
Fig. 6.16 Grey and white matter of part of the spinal cord sectioned across its length. Very
Multiple sclerosis In this
low magnification.
condition the immune system
attacks the myelin sheaths of
nerves in the CNS. The cause is
unknown. The demyelination
Axon of neuron
leads to lack of motor and
sensory coordination. The attacks
Endoneurium
may be single or sequential, and
the degree of disability varies
between patients and at different
Perineurium times during the life of individual
patients.
Axons
Epineurium
Peripheral
nerve
Fig. 6.17 Arrangement of the three connective tissue layers around cytoplasmic processes of
neurons (axons and dendrites) in a typical peripheral nerve.
Summary
Nerve tissue
■ consists of neurons (nerve cells), glial cells and satellite cells.
The nervous system comprises:

■ the central nervous system (CNS) (brain and spinal cord)
■ the peripheral nervous system (PNS) (nerve tissue not in the CNS).
The nervous system has two functional components:
■ the somatic nervous system that detects sensations and controls the contraction of skeletal muscle
■ the autonomic nervous system that controls the contraction of cardiac and smooth muscle and the secretory activity of many glands.
Neurons
■ Neurons mostly have large cell bodies (perikarya) with granular cytoplasm owing to RER involved in protein synthesis.
■ They have cytoplasmic processes (usually many dendrites which transmit nerve (electrical) impulses to their perikaryon and a single axon
which transmits signals away from the perikaryon).
■ They transmit impulses fastest along axons ensheathed in myelin formed by Schwann cells in the PNS and oligodendrocytes in the CNS.
■ Sensory signals are transmitted by afferent neurons to the CNS and efferent neurons carry impulses away from the CNS which affect the
function of, for example, muscles.
Synapses
■ These are specialised junctions between neurons or between neurons and other cell types.
■ A nerve impulse reaching a synapse stimulates the release of neurotransmitter molecules into the synaptic cleft between the pre- and
postsynaptic cells. Neurotransmitters stimulate the postsynaptic cells to transmit a nerve impulse (if they are neurons), or to contract (if
they are muscle cells), or to secrete or to stop secreting (if they are gland cells).
Ganglia and nuclei

■ Ganglia are groups of neuronal cells bodies in the PNS; nuclei are collections of neuronal cell bodies in the CNS.
■ Spinal ganglia are part of the somatic nervous system.
■ Autonomic ganglia are part of the autonomic nervous system. Sympathetic ganglia are involved in fright, fight and flight responses.
Parasympathetic ganglia are involved in rest and digest activities.
Types of glial cell

■ Astrocytes are small cells involved in forming a structural and functional barrier between the blood and the brain.
■ Oligodendrocytes form myelin sheaths around some axons in the CNS.
■ Microglia are able to aid repair of damaged tissue.
42
Chapter 7
The skin
Skin is considered to be the largest in the skin varies and this too helps 7.3). It is made up of keratinocytes, the
organ. It covers the whole surface of the in regulating heat loss and thus body protein keratin and other specialised
body and is continuous at entry and temperature. Skin also has important cell types (see below). Extending through
exits points of the body with the mucous roles as a sense organ detecting stimuli the epidermis in many regions of the
membranes lining the nose, mouth and through specific sensory nerve recep- body are hairs (see below) and spiral
anus, and the reproductive and urinary tors. In addition, cells in the surface of channels which end as pores and allow
openings. Skin on the eyelids is replaced skin exposed to sunlight are involved in for the passage of sweat (Fig. 7.3).
on the inner surfaces of the lids by the the production of vitamin D. The epidermis may be described in
moist epithelium of the conjunctiva. At The skin consists of two layers: the five layers, though all layers are present
the ear the skin continues into the exter- superficial epidermis (the epithelium of only in thick skin, such as on the palms
nal acoustic meatus and is continuous skin) and the deeper dermis consisting of the hand and soles of the feet.
with the tympanic membrane which mainly of connective tissue (Figs 7.1 and
separates the outer ear from the middle 7.2). The dermis is superficial to the ■ Stratum corneum. This is the most
ear. hypodermis and the latter is not consid- superficial layer and consists of the
All four types of primary tissue (epi- ered to be part of the skin. The hypo- protein keratin; no cells are present.
thelial, connective, muscle and nerve) dermis is composed mainly of connective In thick skin (Fig. 7.3) the keratin is
are present in the skin and its functions tissue, which may contain large numbers in numerous layers; there is less
are related to its structure. The skin has of adipose cells; the hypodermis is also keratin in thin skin (Fig. 7.2). Keratin
roles in protection against microbes, known as superficial fascia or subcuta- is a filamentous protein produced by
physical and chemical damage and UV neous tissue. keratinocytes in deeper layers of the
radiation; it also prevents excess water epidermis. It confers toughness and
loss. Skin plays an important role in protection on the epidermis and
Epidermis
regulating body temperature by the helps to prevent water loss and
ability of sweat glands to secrete sweat The epidermis is derived from the ecto- dehydration of cells in the epidermis
onto the surface of the skin which cools derm germ layer of the embryo and is (and deeper). Some keratinocytes in
the body as it evaporates. In addition, composed of a stratified, squamous, deeper layers produce lipids which
the amount of blood flowing in vessels keratinised epithelium (Figs 7.2 and are added to the stratum corneum,
Hair shaft
Keratin
Epidermis
Papillary layer of dermis
Sebaceous
gland
Sweat gland duct Dermis
Arrector pili
muscle
Reticular layer of dermis
Hair follicle
Internal root sheath

Merocrine sweat gland External root sheath
Hypodermis
Hair papilla
Hair bulb
Blood vessels
Fig. 7.1 The structure of skin, including a hair follicle, sebaceous and sweat glands and an arrector pili muscle.
The skin 43
Fig. 7.2 Skin (thin). At the junction of the

epidermis and the connective tissue (green) of Keratin
the dermis interdigitations occur which help bind
the layers together. The interdigitations may be
Epidermis
ridges or papillae; only by examining adjacent
sections would their three-dimensional shape be
revealed. Small blood vessels in the dermis supply
oxygen and nutrients to the epidermis. Special
stain. Medium magnification. Blood vessel
Interdigitation
Dermis (papillary layer)
Dermis (reticular layer)
Fig. 7.3 Skin (thick). A sweat gland duct passes

Spiral channel
sweat from a sweat gland (not shown) to a pore
on the surface of the skin via a spiralling channel
in the keratin. Low magnification.
Keratin
Epidermis
Interdigitation
Duct of sweat gland
Dermis (reticular layer)

and this increases the ability of skin thickest layer of the epidermis, and spinosum. Over a period of about 30
to resist water absorption. The is characterised by the presence of days, keratinocytes produced by
surface of the stratum corneum is ‘prickle’ cells (Fig. 7.4). The angular mitosis in the stratum germinativum
constantly being shed, particularly appearance of these keratinocytes in migrate towards the surface of skin,
if it is subjected to abrasion. sectioned material is due to the large die and the keratin they have
Importantly, the stratum corneum is number of desmosomes between formed is shed.
constantly being added to as cells in adjacent keratinocytes, which are
Within the epidermis there are various
the deeper layers move towards the important in holding the cells
cell types in addition to keratinocytes.
surface at a rate which equals the together and resisting shearing
rate at which the keratin is forces. Increasing amounts of ■ Merkel cells. These cells are scattered
shed. cytoplasmic keratin filaments are throughout the stratum
■ Stratum lucidum. This is a thin layer produced by keratinocytes in this germinativum and are thought to act
of keratinocytes, adjacent to the layer. The uppermost cells in this as mechanoreceptors.
stratum corneum, that are at the end layer develop keratohyalin granules, ■ Langerhans cells. These cells are
stage of their lives. The cells are move towards the surface and derived from bone marrow cells and
packed with keratin and do not become part of the stratum they have an immunological
possess nuclei or organelles. They granulosum. function (Chapter 8). They are
lose their cell membrane and ■ Stratum germinativum. This is the mainly located in the stratum
become the basal layer of the deepest layer of the epidermis and spinosum.
stratum corneum. The change is consists of cuboidal epithelial cells ■ Melanocytes. These cells produce
rapid and the layer is seen only in (Fig. 7.4). The basal cells in the pigment and are present in the
the thickest skin. stratum germinativum are attached stratum germinativum between the
■ Stratum granulosum. This layer may to the basement membrane of the mitotically active cells. Melanin is
be up to five cells deep, but in thin epidermis, which, in turn, is adjacent responsible for giving skin a
skin it may be absent. It is to the dermis. The cells in this brownish colour and carotene for
characterised by the presence of stratum undergo mitosis and are the giving it a yellowish colour. The type
cytoplasmic granules of keratohyalin stem cells of the epidermis. Some and amount of pigment present is
(Fig. 7.4). Other cytoplasmic granules offspring cells remain in this layer, affected by the genetic make-up of
contain lipids and these are released undergo further mitotic activity, and the individual and, in the case of
into extracellular spaces and confer thus continue as stem cells. Other melanin, the amount of exposure to
waterproofing on the superficial offspring cells begin to produce ultraviolet light (sunlight stimulates
layers of the epidermis. Upper cells keratin filaments and migrate the synthesis and spread of
in this stratum die and then become towards the surface of the epidermis; melanin). Melanocytes have long
part of the stratum lucidum. this initially replaces the cytoplasmic processes in which the
■ Stratum spinosum. This is the keratinocytes in the stratum melanin granules are present. They
Keratin Fig. 7.4 Skin. As keratohyalin granules

accumulate in cells in the stratum granulosum
they obscure structural detail; early stages with
few distinct granules and later stages are present.
Keratinocytes in the stratum spinosum appear to
Two cells in stratum granulosum be surrounded by thin, palely stained regions and
have a ‘prickly’ appearance with angular outlines.
High magnification.
Keratinocytes in stratum spinosum
Keratinocytes in stratum
germinativum

The skin 45
also pass melanin to keratinocytes. attachment of the epidermis and the than in the papillary layer.
The melanin is often located in the dermis is strengthened. The
cytoplasm of keratinocytes between papillary layer is characterised by
the nucleus and the surface of the loose connective tissue, including Glands of skin
skin (Fig. 7.5); there, it helps protect collagen, reticulin and elastin fibres Exocrine glands are present in skin.
DNA from damage by UV light. and fibroblasts. There are also the Some secrete sweat and are involved in
transient cell types typical of temperature regulation. Others, seba-
connective tissue, e.g. white blood ceous glands, secrete lipids and most are
cells (Chapters 4 and 8). In the associated with hairs. In females, modi-
Dermis papillary region there are blood fied glands in the skin (mammary
vessels that supply oxygen and glands) are able to secrete milk in
The dermis is derived from the meso-
nutrients to nearby cells, including response to the hormones present
derm layer of the embryo and consists
epidermal cells, and that are also during and after pregnancy (Chapter
largely of connective tissue fibres and
involved in temperature regulation. 16).
cells. Also present in the dermis are
Some sensory nerve endings are
structures which may extend between
present in the papillary region of the Sweat glands
the hypodermis and the epidermis, e.g.
dermis. ■ Merocrine sweat glands. These are
parts of developing hairs in hair follicles,
■ Reticular layer. The reticular layer is present in skin (Figs 7.1 and 7.6) all
sebaceous glands and sweat glands (see
deep to the papillary layer but the over the body and they are simple,
below). The dermis is divided into two
border between them is a gradual coiled tubular glands (Chapter 3).
layers, the papillary and the reticular
transition: it connects the skin to the The secretory cells are located deep
layer.
underlying hypodermis. Dense, in the dermis, and even in the
■ Papillary layer. This is the most irregular connective tissue (Figs 7.2 underlying hypodermis. An
superficial layer and it interdigitates and 7.3) containing many collagen epithelial lined duct (Fig. 7.3) drains
with the epidermis through a series fibres is predominant in the reticular each gland and it passes to the
of dermal ridges and papillae (Figs layer. The transient cell population superficial layer of the epidermis
7.2 and 7.3). In this way, the is less abundant in the reticular layer (stratum corneum). The duct is
replaced by a spiral channel through
the stratum corneum (Fig. 7.3) and
opens at a pore on the surface of the
Keratin skin. Merocrine sweat glands are
innervated by sympathetic nerves
and may be stimulated to secrete
under conditions of stress, as well as
in order to cool the body.
Myoepithelial cells surrounding the
gland cells contract and assist in the
Melanin triangular ‘caps’ over
expulsion of sweat.
keratinocytes
■ Apocrine sweat glands. This type of
sweat gland is present in the axilla,
around nipples and in the anal
region. The glands are larger than
merocrine sweat glands, and they
are located more deeply in the
dermis and underlying hypodermis.
Unlike merocrine glands, apocrine
Melanin triangular ‘caps’ over sweat glands do not secrete onto the
keratinocytes surface of the skin; instead, they
secrete around developing hairs in
Dermis hair follicles. Secretion by apocrine
sweat glands is influenced by sex
hormones, and, after bacterial action,
their secretions have a characteristic
Melanin in cells in basal layers odour. It is thought that this odour
may impart pheromone-like qualities
to the secretion.
Sebaceous glands
■ Sebaceous glands (Figs 7.1 and 7.7)
secrete a lipid-based substance
Fig. 7.5 Skin (pigmented with melanin). Melanin is visible in some of the keratinocytes ‘capping’ known as sebum. They release their
the nucleus and forming a barrier to UV light. The melanin is formed in melanocytes in basal layers secretions by the holocrine method
although the precise identity of these cells is not revealed at this magnification. Special stain. High and as the cells die the sebum is
magnification.
glands open directly onto the surface

of the skin and help maintain its
texture and condition.
Hair follicles
Hair is formed largely of a compact,
Lumen of sweat gland duct
dense form of keratin. Each hair is pro-
duced in a structure known as a hair
follicle (Fig. 7.1). Hairs are widespread
Connective tissue over the body surface though they are
absent from the palms, soles, parts of
the genitalia, tips of fingers and toes,
and lips. Hairs are of two types: vellus
hairs, which are the short, fine, soft hairs
Lumen of sweat gland secretory on the skin, and terminal hairs, which
tubule
are the long hairs such as on the scalp.
Hairs may be coloured, e.g. by the pres-
ence of a pigment such as melanin.
Hair follicles develop as cylindrical
Nuclei of epithelial cells (secreting invaginations of the epidermis and they
sweat) extend into the dermis and, in some
instances, also into the hypodermis.
Straight hair grows from straight folli-
cles, and spiralling follicles give rise to
Fig. 7.6 Sweat gland. Secretory epithelial cells lining the coiled tube forming a sweat gland appear curly hairs. Hair follicles are surrounded
palely stained with eosin in comparison with the cells lining the ducts. Connective tissue supports the
by connective tissue (Fig. 7.8). During the
epithelial cells forming the gland. High magnification.
growing phase of a hair the base of its
follicle is expanded into a bulbous
portion (Figs 7.8 and 7.9). Cell prolifera-
tion in the epidermal-like cells of the
bulb produces a variety of cells. Some of
these cells form part of the follicle and
move towards the surface and others,
centrally placed, form the hair which
External and internal root sheaths grows out from the follicle. Pigment
such as melanin in cells in this region
(Fig. 7.9) affect the colour of the hair.
Each hair bulb is invaginated by a dermal
papilla of connective tissue (Fig. 7.9) con-
Arrector pili muscle taining blood vessels which are essential
for hair growth.
Each hair follicle is lined by layers of
Sebaceous gland
cells similar to epidermal cells, and by
cells produced by mitosis of cells in the
hair bulb. The outer layers of epidermal-
like cells are known as the external root
sheath (Figs 7.1 and 7.9). An inner
sheath, formed by cells produced in the
Dermis hair bulb, extends only part way along
the follicle. It is the innermost cells
within the inner sheath which undergo
keratinisation and form the hair shaft.
External root sheath
At the region where the inner sheath
Fig. 7.7 Part of a hair follicle, sebaceous gland and smooth muscle cells. The developing hair stops, secretions from sebaceous glands
has been lost during processing. The space it occupied and an arrow shows the direction along which drain into the follicle (Fig. 7.7) and coat
it would have grown. Connective tissue is stained green. Special stain. Medium magnification. the hair as it grows out of the
follicle.
released from the cytoplasm and puberty. In areas where there are Hair growth is cyclical. Growth in
empty spaces may be apparent in hairs, sebaceous glands secrete into length usually occurs for several years
the gland. The activity of sebaceous the follicle of each hair (see below) and then the follicle enters a rest phase
glands is influenced by sex and the sebum ‘conditions’ the hair. when mitosis in the bulb region
hormones and their secretory In locations where there are no hairs stops and the bulb shrinks in size. In the
activity increases substantially after (e.g. the palms and soles) sebaceous rest phase, the hair eventually falls
The skin 47
out of the follicle and, after several

weeks, mitosis in the bulb begins and
this new growth phase produces another
hair.
Hair follicle (sectioned obliquely) Muscles, nerves and blood

vessels in the dermis
and hypodermis
Smooth muscle cells, known as arrec-
tores pilorum, are associated with hair
follicles and their sebaceous glands (Figs
Hair in follicle (sectioned 7.1 and 7.7). The muscle cells lie obliquely
longitudinally) and attach the hair follicle to connective
tissue in the dermis. Sympathetic nerves
stimulate contraction of these smooth
muscle cells and this causes hairs to
‘stand on end’. Sympathetic nerves also
supply sweat glands and the smooth
Hair bulb muscle cells in the walls of blood vessels
in the skin. The flow of blood through
vessels in skin and the amount of sweat
secreted varies, particularly as a means
of maintaining body temperature by
Hair in follicle (sectioned varying heat loss from the body. Other
obliquely) nerves in skin transmit sensory informa-
tion to the CNS. There are several types
of nerve ending in skin that may be
distinguished by their morphology
and these include free nerve endings,
Pacinian corpuscles, Meissner’s corpus-
Fig. 7.8 Hair. Several hair follicles have been sectioned, only one along its length from the hair bulb cles and Merkel cells. The free nerve
to the surface. Hair appears yellowish and keratin of the stratum corneum reddish. Connective tissue is
stained green. Special stain. Very low magnification.
endings detect pain and temperature
changes. Pacinian corpuscles (Chapter 6,
Fig. 6.11) have a characteristic lamellated
appearance enclosing a central nerve
ending and they detect pressure changes.
Meissner’s corpuscles are located in
dermal papillae and detect touch. Merkel
Developing hair cells also detect touch and are located in
the epidermis.
External root sheath
Internal root sheath
Melanin in cells
Dermal papilla
Connective tissue
Fig. 7.9 Hair bulb. Melanocytes are present among the epithelial cells in the bulb and melanin can
be distinguished as dark brown material. (The precise detail of melanin in cells is not seen at this
magnification.) Connective tissue of the dermis extends as a papilla into the hair bulb. Special stain.
Clinical notes
Psoriasis This is a condition in which there is overproliferation of keratinocytes. This results in patches of
thick, silvery, scaly lesions particularly on the scalp, knees and elbows. The cause is unknown.
Age With age, numerous changes occur in skin. In particular, elastin fibres disappear so the skin loses the ability to
recoil after being stretched. The epidermis becomes thinner with age and less able to withstand trauma.
Tumours Tumours of the skin may be benign or malignant. Of the benign tumours, warts (papillomata) are
common. Warts occur at any site, and are simple proliferations of epidermal cells resulting from infection of the
keratinocytes with a papilloma virus. Basal cell carcinomas of skin are common neoplasms which rarely spread to
distant sites. However, they spread into the dermis and can cause damage in the local region. Of all the skin tumours
the most malignant are malignant melanomas (neoplasms of melanocytes) and they often have fatal consequences.
Summary
Skin:
■ is an organ covering the body and consists of epidermis and dermis

■ is involved in protection against physical trauma, dehydration, ultraviolet light, harmful molecules and microorganisms
■ aids control of body temperature
■ by secretion of sweat and variation in blood flow through blood vessels near the surface of the skin
■ has sensory nerve receptors
■ is involved in producing vitamin D.
The epidermis is a stratified, squamous, keratinised epithelium:
■ the basal layer of cells (keratinocytes) act as stem cells

■ keratinocytes move from the basal layer, differentiate, make keratin and die, and keratin is shed
■ other cells in the epithelium make pigment, others are involved in immune responses.
The dermis consists mainly of connective tissue cells and fibres:
■ it has a papillary layer adjacent to the epidermis and a denser, reticular layer adjacent to the hypodermis.
Sweat glands (in most regions of the body):
■ consist of secretory cells lining coiled tubes in the dermis or hypodermis

■ secrete sweat by the merocrine method under the influence of sympathetic nerves and aid the regulation of body temperature.
Sebaceous glands synthesise and secrete lipids forming sebum:
■ secretion occurs by the holocrine method and is affected by sex hormones

■ most secretions coat developing hairs.
Hair:
■ is a compact, dense form of keratin and develops in a hair follicle

■ follicles extend between the surface of skin and the dermis or hypodermis
■ actively growing hair follicles have mitotically active cells at the base
■ cells move from the base towards the skin surface, some form the hair
■ smooth muscle attached to hair follicles, under control of sympathetic nerves, can make hairs ‘stand on end’.
49
Chapter 8
The blood and immune system
Blood and the immune system contain of individual blood cells may not readily
a wide variety of cells and carry out
Blood be distinguished (Fig. 8.1). To study
diverse functions. All the components of Blood consists of cells and parts of blood cells in detail it is usual to spread
blood and the immune system may be cells suspended in a fluid, the plasma. blood onto a glass microscope slide, a
considered as connective tissue and the The cellular components of blood are process which makes a ‘blood smear’.
vast majority of the cells is derived from red and white blood cells (respectively, Smears display the whole of the cells as
mesoderm. Blood flows around the erythrocytes and leucocytes) and parts opposed to cells in histological sections
body in tubes known as blood vessels of cells, platelets (thrombocytes). Plasma which may have been sliced during
(Chapter 10) and is involved in moving is a straw-coloured fluid that contains preparation (and show only part of indi-
cells and molecules. Tissue fluid (extra- electrolytes, carbohydrates, lipids and vidual cells).
cellular fluid), which bathes many of the proteins (including albumin and globu-
cells in the body, is the aqueous compo- lins); however, plasma is mainly water. Erythrocytes (red blood cells)
nent of extracellular matrix (Chapter 4) Erythrocytes constitute just over 40% of An erythrocyte is a membrane-bound
and is formed from blood. The immune blood volume with just 1% leucocytes; cytoplasmic structure which does not
system protects the body from invasion most of the rest is plasma. have a nucleus. Erythrocytes lose their
and damage by microorganisms and Although blood is considered to be a nuclei during their formation in bone
from many potentially harmful mole- form of connective tissue in which the marrow, just before they are released
cules. This system recognises cells and extracellular matrix is the fluid plasma, into blood vessels. Mature erythrocytes
molecules ‘foreign’ to the body and the function of blood differs from the are biconcave discs approximately 7 μm
generates immune cells and molecules functions of other forms of connective in diameter but are easily distorted and
in defensive immune responses. The tissue. Blood circulates via the cardio- are able to pass along narrow blood
immune system involves a wide variety vascular system and delivers oxygen and vessels about 3.5 μm in diameter. Iden-
of cells and molecules including non- various molecules, including nutrients tifying red blood cells and knowing
specialised and specialised cells and and hormones, to cells of the body. their maximum diameter can be used as
molecules which carry out immune Blood also facilitates the removal of a scale for assessing the size of other
responses. The molecules vary in size waste molecules from body tissues, features in histological specimens (Fig.
and type but many are large protein including carbon dioxide. Importantly, 8.1). In blood smears, erythrocytes
molecules such as antibodies which blood is able to coagulate and prevent usually appear rounded and many have
react specifically with other molecules excessive blood loss if blood vessels are palely stained centres reflecting their
(antigens). Blood plays a major role in damaged. central, thinner region of cytoplasm
transporting immune cells and antibod- The ability of blood to deliver mole- (Figs 8.2–8.4).
ies around the body. cules to and remove other molecules Erythrocytes transport oxygen from
The cellular components of the from the body is facilitated by blood the lungs to the other parts of the body.
immune system, as well as circulating in forming tissue fluid (extracellular fluid). The majority of their cytoplasm is made
blood, are widely distributed through- Some of the plasma fluid (and the up of the iron-containing protein
out organs of the body and are pre- smaller molecules it contains) leaves haemoglobin and only a few organelles
dominant in specialised organs (e.g. blood vessels via the endothelial cells (mitochondria and ribosomes) are
the thymus and spleen). Immune cells lining small blood vessels and bathes present. Erythrocytes are referred to as
are also present in large numbers surrounding cells in tissue fluid. White red blood cells because the iron of
in lymph nodes, structures which blood cells also leave small blood vessels haemoglobin confers the red colour on
are integral parts of the circulatory and these are particularly important in blood. Oxygen has a high affinity for the
system that return excess tissue fluid the defence mechanisms provided by iron in haemoglobin in locations where
to blood (see below and Chapter 10). the immune system. Some tissue fluid there is a high oxygen concentration,
Localised clusters of immune cells are and white blood cells eventually return such as the lungs. In regions with rela-
present in other regions of the body, to blood via a series of lymphatic vessels tively low oxygen concentrations, such
particularly where mucosal surfaces and lymph nodes (see below). as in most body regions other than the
are exposed to harmful molecules and lungs, the oxygen is liberated and used
organisms in the environment (e.g. Blood cells in metabolic processes. The reverse is
substances ingested into the digestive Blood cells in routine histological sec- true of carbon dioxide, a waste product
tract or breathed into the respiratory tions may be identified as individual of glucose metabolism. It is the globin
tract). cells. However, in many instances details (the protein component of haemo-
Fig. 8.1 Liver. The red blood cells in some

blood vessels can be identified as individual
structures and the largest diameter taken as
7 μm. In other vessels, individual red blood cells
cannot be distinguished but they stain a similar
shade of red with eosin. White blood cells in
Plasma proteins
blood vessels in sections at this magnification can
be identified only by their densely stained nuclei.
Plasma proteins fixed in the lumen of the large
vessel stain lightly with eosin. Medium
magnification.
Red blood cells in small vessel
Nuclei of liver cells
White blood cell
Red blood cells in vein
Red blood cells (individual cells not

visible)
Platelet
globin) that carries some of the carbon

dioxide from body tissues to the lungs.
Erythrocytes have a life span of
approximately 120 days and after this
time they are destroyed by cells in the
liver, spleen and bone marrow, probably
because they become less able to change
shape. The rate of production of new
erythrocytes from the bone marrow
normally equals the rate at which they
are destroyed. Any loss of blood from
Nucleus of monocyte Red blood cell
the circulation, as a result of trauma for
Fig. 8.4 Blood smear. Red blood cells, example, is followed by an increase in
Red blood cells Neutrophil (with Barr body) monocyte. Special stain. Very high magnification.
Fig. 8.2 Blood smear. Red blood cells, neutrophil, the production of erythrocytes and their
platelets. Special stain. Very high magnification. release into circulation until normal
numbers in blood are restored.
Nucleus of small
lymphocyte Clinical note
Anaemia This common blood disorder occurs when there is not
enough haemoglobin to supply oxygen to support the metabolic
requirements of the body’s cells. An anaemic person may look pale, feel
weak and easily become short of breath. The most common cause of
anaemia is a shortage of iron, the element essential for the formation and
function of haemoglobin. Excessively heavy blood loss, e.g. at menstruation,
may be a cause of anaemia as enough iron may not be available to support
Red blood cell red blood cell production at a rate which replaces the losses, particularly if
the losses have occurred repeatedly over many months.
Other types of anaemia have a genetic basis. For example, in sickle cell
anaemia the haemoglobin molecule is abnormal. In regions of the body in
Nucleus of which oxygen levels are low the haemoglobin molecule becomes rigid and
eosinophil the red blood cells become less flexible and take on the shape of a sickle. As
a result, many red blood cells die prematurely in the spleen or they may
Fig. 8.3 Blood smear. Red blood cells, block small vessels around the body. Life expectancy is likely to be
eosinophil, small lymphocyte. Special stain. Very considerably reduced.
high magnification.
The blood and immune system 51
Leucocytes (white blood cells) into circulation from the bone the lymphocytes in peripheral blood
Leucocytes are referred to as white blood marrow. and they are distinguished by having
cells because of their whitish or buff ■ Eosinophils. An eosinophil is a densely stained nucleus that
colour in the zone between plasma and characterised by its bi-lobed nucleus occupies the bulk of the cell (Fig.
red blood cells after centrifugation of and by numerous granules which 8.3). Lymphocytes responding to an
blood (a process used to determine the stain heavily pink with eosin and immune stimulus are larger than
proportion of red cells in blood). Leuco- with the staining methods for small lymphocytes and have
cytes are categorised by their content of examining blood smears (Fig. 8.3). relatively more cytoplasm – they are
cytoplasmic granules and by their nuclear Lysosomes are also present in described as medium or large
morphology. Leucocytes with granules eosinophils. Eosinophils develop in lymphocytes.
are known as granulocytes and their bone marrow and normally Lymphocytes are also categorised
nuclei have two or more lobes. Granulo- constitute 2–4% of the leucocytes according to their function. Their
cytes are subdivided into three categories present in peripheral blood. morphology does not distinguish the
by the affinity of their granules for certain Eosinophils function by their ability functional types but categories can be
dyes. Leucocytes without granules are to respond to antigen–antibody identified by using labelled antibodies
known as agranulocytes. There are two complexes and to parasites. Their to identify specific molecules on their
categories of agranulocyte: lymphocytes, granules release their contents which cell membrane. The categories are B
which each have a spherical nucleus, and bind to, and kill, parasites. They are lymphocytes, T lymphocytes and
monocytes, which each have an indented, able to phagocytose and digest natural killer (NK) cells.
spherical nucleus. antigen–antibody complexes and the
remains of parasites. In addition, ■ B lymphocytes constitute 5–15% of
Granulocytes they release antihistamines that small lymphocytes in peripheral
■ Neutrophils. These constitute about reduce the inflammatory processes blood. They migrate out of blood
70% of the total leucocyte that are initiated by such complexes vessels and through body tissues
population in peripheral blood. and organisms. Eosinophils are and respond to antigenic
Neutrophils are also known as present in increased numbers in stimulation by increasing in size
polymorphonuclear leucocytes blood and body tissues during and differentiating into plasma
(PMNLs) because each has a allergic reactions, such as hay fever, cells (see below).
multilobed nucleus (Fig. 8.2). The and in response to infections by ■ T lymphocytes constitute 65–75%
nuclei of neutrophils in females are parasites. of small lymphocytes in peripheral
characterised by the possession of a ■ Basophils. The granules of basophils blood. They are small when they
Barr body (Fig. 8.2), which is are stained by basic dyes such as are inactive but differentiate into
manifest as a small drumstick haematoxylin. The nuclei of larger lymphocytes when
projection from one of the lobes of basophils are bi-lobed but the responding to immune
the nucleus. Barr bodies represent granules are often so numerous that stimulation. T lymphocytes are
the inactive second X chromosome they obscure the rest of the responsible for cell-mediated
of females, but they are seen on only cytoplasm and the nucleus in blood immunity, which is the type of
a small proportion of neutrophil smears. Basophils develop in bone cellular immune response engaged
nuclei. The granules of neutrophils marrow and they constitute only in detecting foreign cells and
do not stain with acidic or basic 0.5–1% of the total leucocyte destroying them. This involves T
dyes. Some of the granules are very population in peripheral blood. They lymphocytes detecting certain
small and not readily seen by light leave the blood and are involved in molecules which may be on the
microscopy. Some are lysosomes initiating inflammatory surface of foreign cells, or on the
and the enzymes they contain are reactions. body’s own cells that have become
typical of lysosomes, e.g. acid abnormal (e.g. malignant or
phosphatase. Agranulocytes infected by virus). This recognition
Neutrophils develop in bone ■Lymphocytes. These make up 20– stimulates the T lymphocytes to
marrow, enter blood vessels and 30% of the total number of divide and increases the number
thus circulate around the body. leucocytes circulating in blood. of T lymphocytes able to attack
However, they migrate out of blood Lymphocytes are also present in specifically and destroy ‘foreign’
vessels within a few days and move bone marrow, thymus, spleen and cells. T lymphocytes also produce
rapidly through body tissues where lymph nodes, and in lymphoid a variety of molecular signals that
normally they die after a few days. If regions in other organs, e.g. in parts regulate other cells involved in
neutrophils encounter bacteria they of the gastrointestinal, urinary, mounting immune responses.
are able to engulf and kill them. reproductive and respiratory tracts. ■ Natural killer (NK) cells comprise
They kill bacteria by a variety of Some lymphocytes develop in bone 10–15% of the lymphocytes in
mechanisms, one of which involves marrow but others are produced in peripheral blood. They are larger
hydrogen peroxide. Neutrophils that the thymus and at other sites in the cells than small lymphocytes and
have performed their killing function body in response to immune stimuli. they have a few granules in their
die and accumulate in pus at the site In general, lymphocytes function at cytoplasm. NK cells migrate
of the infection. If the infection such sites, and not in peripheral through body tissues and have the
persists, large numbers of blood. ability to detect and kill foreign
neutrophils leave blood and are Lymphocytes may be described as cells. Their activity is regulated by
attracted to the site(s) of infection small, medium or large. Small factors produced by subsets of T
and large numbers are also released lymphocytes make up about 95% of lymphocytes.
■ Monocytes. Monocytes are derived

from precursor cells in bone marrow Clinical note
and constitute about 5% of the White blood cell disorders Increased numbers of normal
leucocytes in blood. They are 15– neutrophils in peripheral blood or other areas of the body may be
20 μm in diameter and their nucleus due to a bacterial infection whereas increased numbers of eosinophils may
appears indented in smears (Fig. be due to a parasitic infection or to an allergic reaction.
8.4). Monocytes leave blood vessels, Leukaemias result from the proliferation of malignant white blood cells in
migrate through tissues and become the bone marrow. Large numbers of white blood cells, which may appear
macrophages (see below). normal or abnormal, enter peripheral blood. Leukaemias are classified
according to the type of white cell produced in high numbers (granulocyte,
Platelets (thrombocytes) lymphocyte or monocyte) and whether the progress of the disease can be
Platelets (Fig. 8.2) are cytoplasmic frag- described as chronic or acute. Chronic leukaemias progress slowly, but in
ments of megakaryocytes, a large cell acute leukaemias the disease process progresses rapidly and many of the
type present in bone marrow (see cells released into the bloodstream appear immature or grossly abnormal.
below). Platelets are released into blood
vessels in bone marrow and they then
circulate around the body. Platelets are
essential for blood clotting and help
control haemorrhage.
Mast cell
Other cells involved in
immune responses
Mast cells
Mast cells are present in connective
tissues of the body and they are densely
packed with granules which may hide
the nucleus (Fig. 8.5). They resemble the
Mast cell and discharged granules
basophils in blood. Mast cells have rec-
eptors for a type of antibody (immuno-
globulin E) on their cell membranes
and these antibodies are produced in
response to allergen(s). A subsequent
exposure to the same allergen(s) causes Fig. 8.5 Mast cells. The two mast cells are intensively stained amongst other cells (connective and
the mast cells to release histamine (a epithelial) which are revealed only by their palely stained nuclei. One mast cell has discharged its
granules. Special stain. High magnification.
vasoactive molecule which affects the
diameter of blood vessels) from their
granules as well as other mediators of
the inflammatory response. This type of
reaction can be rapid and fatal and is
known as an anaphylactic reaction.
Plasma cells
Plasma cells are often evident at sites of
infection associated with chronic inflam-
mation and in lymph nodes (see below).
They are the end stage of differentiation
of B lymphocytes and they mount a Plasma cell nucleus
humoral immune response by produc-
ing specific antibodies (e.g. immuno-
globulins A and G) to specific antigens.
Plasma cells may appear ovoid in shape,
are larger than the B lymphocytes and
are identified by the eccentric position
of their nucleus (Fig. 8.6). The cytoplasm Plasma cell nucleus
of each plasma cell has large amounts
of rough endoplasmic reticulum syn-
thesising a particular immunoglobulin
which functions as a specific antibody.
The antibody molecules are released
from plasma cells and circulate in tissue
fluids, lymph and peripheral blood Fig. 8.6 Plasma cells in the medulla of a lymph node. The plasma cells have pinkish cytoplasm
where they are able to react with their (reflecting the antibody proteins they contain) and some display an eccentric nucleus. High
specific antigen(s). magnification.
Macrophages lymphocytes are directed specifically Within bone marrow blood flows in
Macrophages are derived from mono- at individual molecules (which may endothelium-lined blood vessels and a
cytes that have migrated out of blood be free or attached to a cell’s reticulin meshwork surrounding the
vessels and many are transient in tissues membrane). Significantly these vessels is packed with developing blood
and organs (e.g. the lungs) and espe- specific immune responses are cells. Macrophages are associated with
cially in loose connective tissues sup- associated with the ability of a the meshwork and they are involved in
porting the parenchymal cells of organs. lymphocyte to ‘remember’ a destroying aged red blood cells. Mega-
In certain organs macrophages are molecule it has encountered. At a karyocytes are also in the meshwork
present at fixed locations, e.g. as Kupffer subsequent meeting with a and they shed fragments of their cyto-
cells in the liver (Chapter 12). ‘remembered’ molecule such plasm, as platelets, into adjacent blood
Macrophages are able to phagocytose lymphocytes rapidly produce an vessels. The appearance of bone marrow
material such as dead cells and bacteria immune response against the in sections reveals few details of the
and inert particles, e.g. carbon. Some of molecule and, importantly, also structure of the developing blood cells
the material they ingest (not carbon) is undergo rapid mitotic activity and smears of bone marrow are exam-
digested in lysosomes and some is producing more lymphocytes which ined for detailed studies. Megakaryo-
presented as antigenic molecules to can also respond to the same cytes, however, can be identified
lymphocytes which then produce an molecule. This type of memory readily in sectioned material by their
immune response. Macrophages which response is known as acquired large size and multilobed nucleus
have taken up inert material, such as immunity. (Fig. 8.7).
carbon, remain in the body and account
Immune cells are produced in the
for the black colour seen in the lungs of
bone marrow, thymus, spleen and Haematopoiesis
many people at post mortem. Macro-
lymph nodes. In addition, there are All blood cells arise from one type of
phage numbers can increase when
numerous sites, particularly in the res- stem cell in bone marrow which resem-
exposure to antigens increases as mono-
piratory, digestive, urinary and repro- bles a small lymphocyte and is described
cytes leave peripheral blood and become
ductive systems, where lymphocytes are as being pluripotent. These stem cells
macrophages.
present in large numbers and are able undergo successive rounds of mitosis
to respond to foreign molecules or and replace themselves and produce
Dendritic cells
microorganisms. cells which are able to differentiate into
(antigen-presenting cells)
different types of cell with restricted
Dendritic cells are derived from cells in
Bone marrow stem cell ability. After several cycles of
bone marrow and they are able to
Bone marrow occupies spaces within mitotic activity the potential to develop
present antigens to lymphocytes and
bones (Chapter 9). Red and white blood into several types of blood cell is
this initiates an immune response. Den-
cells and platelets develop in bone restricted and unipotent stem cells
dritic cells exhibit fine cytoplasmic proc-
marrow in a process known as haemato- develop. Unipotent stem cells are com-
esses which increase their surface area
poiesis. In regions where haemato- mitted to produce one type of blood cell
and hence the area available for antigen
poiesis occurs the marrow appears red (and replace themselves). Unipotent
binding. They are present in the sup-
to the unaided eye. With age, many of stem cells are categorised by the type of
porting connective tissue of many paren-
the haematopoietic regions are replaced blood cell they produce. For details of
chymal organs and in lymph nodes.
by adipose cells which give marrow a the stages in the formation of erythro-
Dendritic cells in the skin are known as
yellow colour. cytes, eosinophils, basophils, neutro-
Langerhans cells and those in the brain
as microglial cells.
The immune system

The immune system may be considered
to have two types of response which
help to protect the body from foreign
Osteocyte
molecules, cells and organisms, includ-
ing viruses, bacteria and parasites. Developing blood cells
■ Non-specific responses. These are

carried out by cells such as
neutrophils and macrophages which Bone matrix
are able to engulf and destroy many
microorganisms and molecules. The
ability of neutrophils to migrate
from blood vessels and find their
Megakaryocyte
way rapidly to sites of infection
produces an acute inflammatory
response which may quickly stop an
infection.
■ Specific responses. The humoral
(fluid) and cell-mediated responses
carried out, respectively, by B and T Fig. 8.7 Bone marrow. Megakaryocyte. High magnification.
phils, monocytes, T lymphocytes and B

lymphocytes, NK cells and megakaryo-
cytes from stem cells, a more detailed
textbook of histology or haematology Nurse cell nucleus
should be consulted.
The rate of production of new blood Hassall’s corpuscle
cells (and platelets) in the bone marrow
normally equals the rate at which each
cell type dies. Some blood cells, e.g. neu-
trophils, live less than a week whereas
red blood cells live for about 120 days.
Some lymphocytes live 10 or more years.
Vast numbers of new blood cells are
produced each day (e.g. about 3 × 109
red blood cells/kg body weight are pro-
duced each day). Most blood cells leave
bone marrow when they are mature by Lymphocytes in medulla
entering blood in vessels in bone
marrow. Some cells, such as neutrophils,
usually stay in the bone marrow for a
few days after they mature and they act
as a reservoir of cells that can rapidly
enter the circulation and migrate to sites
of infection.
Thymus
The thymus is an organ in the mid-line
of the upper anterior part of the thorax
which is prominent in young children Blood in vessel
and gradually regresses after puberty.
It is covered by a connective tissue
capsule and has a fine meshwork which
Lymphocytes in cortex
extends throughout the thymus. Unusu-
ally, the meshwork is formed by epithe-
lial, not connective tissue, cells. The
epithelial mesh supports lymphocytes
and two regions, a peripheral cortex and
inner medulla, are described. Virtually Fig. 8.8 Thymus, cortex and medulla. Medium magnification
all of the lymphocytes in the thymus are
in direct contact with the epithelial
meshwork and the epithelial cells
immunologically competent, i.e. able petent. The mature T lymphocytes in
are sometimes referred to as ‘nurse’
to produce immune responses to the medulla are released into blood
cells.
attack foreign molecules, cells and vessels. They live for many years and
Lymphocytes are densely packed in
organisms many leave the blood vessels and migrate
the meshwork in the cortex (Fig. 8.8). In
■ to ensure that immature T through tissues where they may be
the medulla, fewer lymphocytes are
lymphocytes also become self- triggered into producing immune
present, and they appear in irregular
tolerant; this process enables T responses.
clumps (Fig. 8.8). The most recognisable
lymphocytes to distinguish ‘self ’
components of the support meshwork
from foreign cells and molecules
are the epithelial cells which form Spleen
and thus avoid attacking ‘self ’ body
whorl-like, lamellated structures in the The spleen lies in the left, upper region
cells and molecules
medulla known as Hassall’s corpuscles of the abdomen. It is the largest lym-
■ to release mature T lymphocytes
(Fig. 8.8). The function of these corpus- phoid organ of the body and it has two
into circulation.
cles is not known. main functions:
The thymus secretes factors that facili- The processes that produce mature T
■ it monitors circulating blood for
tate its functions. The functions are par- lymphocytes involve the generation of
foreign material, particularly bacteria,
ticularly important in the early stages of many new T lymphocytes by mitosis of
and ensures immune responses
life and they are: the T lymphocytes in the cortex of the
develop to such material
thymus. Many of these new lymphocytes
■ it destroys aged red blood cells,
■ to provide an environment to receive die; these are thought to be T lym-
probably when they have become
immature T lymphocytes from bone phocytes which are not self-tolerant.
relatively rigid.
marrow Other T lymphocytes move towards the
■ to ensure that immature T medulla as they mature and become The spleen has a connective tissue
lymphocytes become self-tolerant and immunologically com- capsule which is covered by a serosal
membrane called the peritoneum

(Chapter 3). Connective tissue strands
(trabeculae) extend from the capsule
Red pulp
into the spleen and these support
branches of arterial blood vessels dis-
tributing blood through the paren-
PALS
chyma. An intricate network of fine
reticulin fibres connected to the trabecu-
lae support the cells in the parenchyma.
Two regions known as the red pulp and
Arteriole (lumen)
white pulp form the parenchyma. With
the unaided eye the white pulp appears
pale and the red pulp appears red: white
cells are predominant in white pulp and
red blood cells predominant in red
pulp. PALS
■ White pulp. White pulp contains

aggregations of lymphocytes packing
the reticular meshwork. Many of the
lymphocytes in white pulp appear
as sheaths around small arteries
(arterioles) distributing blood
through the spleen. This
arrangement is known as a
periarteriolar lymphatic sheath
(PALS) and is unique to the spleen. Fig. 8.9 Spleen, red pulp and white pulp with periarteriolar lymphatic sheath (PALS). Medium
These blood vessels are known as magnification
central arterioles although they do
not always appear to be in the
centre of a sheath of lymphocytes
(Fig. 8.9). T lymphocytes are
predominant in PALS. If Clinical note
lymphocytes in the spleen are Autoimmune disorders These are caused by inappropriate
responding to foreign material in immune responses generated against the body’s own molecules
blood, spherical clusters (follicles) of (which may be free or on cell membranes). In myasthenia gravis, a condition
B lymphocytes appear in the white in which muscle weakness and fatigue occurs, autoantibodies are detectable
pulp adjacent to PALS. These are (in most patients) which interfere with synapses at neuromuscular junctions.
similar in form and function to
lymphoid follicles in lymph nodes
(see below).
Some of the blood from central the meshwork of the red pulp; this Lymphatic vessels
arterioles passes into endothelial- is described as an open circulation. Lymphatic vessels are lined by endothe-
lined blood vessels (also known as Blood in red pulp passes among lial cells and they begin as very small
sinuses or sinusoids) in the white antigen-presenting cells, blind-ended tubes in most regions of the
pulp. These are relatively large macrophages and lymphocytes and body. They serve to drain excess tissue
spaces where blood moves slowly then returns into endothelium-lined fluid and transmit it through lymph
and blood cells, antigens and sinuses. This passage through the nodes before it returns to peripheral
particulate matter intermingle. red pulp enables immune responses blood in blood vessels (Chapter 10).
Macrophages attack any to foreign molecules to develop and The fluid in lymph vessels is known
microorganisms present and ageing red blood cells and platelets as lymph. Valves in lymphatic vessels
macrophages and other antigen- to be detected and destroyed. ensure drainage of lymph is unidirec-
presenting cells screen particulate Macrophages ingest and digest the tional, away from an organ or region of
matter for foreign antigens and debris from dead cells and useful the body.
‘present’ them to lymphocytes which molecules circulate in blood and are
then mount immune responses. reused. The blood in sinuses drains Lymph nodes
■ Red pulp. Red pulp fills the spaces into venules (small veins) which join Lymph nodes are aggregations of lym-
between white pulp. It receives together and leave the spleen at the phocytes where lymph is monitored for
blood that has passed through the hilum. In addition, a closed foreign molecules (e.g. in lymph or on
central arterioles of the white pulp. circulation may also exist in humans bacteria, viruses or tumour cells) and
The vascular arrangement of the whereby blood does not leave the where specific immune responses are
spleen is unusual (in humans) in vessels; instead, it remains in the generated as a result. Lymph nodes
that some blood and blood cells leak endothelium-lined sinuses which occur in defined anatomical sites where
from the sinuses and pass through connect arterioles with venules. they receive lymph, which is draining
tissue fluid from specific regions of the the region between the cortex and by being lined by cuboidal
body. Lymph nodes, sometimes known the medulla (the paracortex) and endothelial cells and is found only
as glands, are roughly bean shaped and interact with T lymphocytes. As a in lymph nodes.
their size depends on whether they result, these B lymphocytes ■ Medulla. The medulla of lymph
are resting or are actively undergoing differentiate into plasma cells (Fig. nodes is composed of numerous
immune responses. In the case of an 8.6) and secrete specific antibodies. endothelium-lined lymph vessels
infection or tumour in a particular part The antibodies leave the node in (sinuses) and medullary cords which
of the body, the draining lymph node(s) efferent lymph. ‘Memory’ B are packed with immune cells (Fig.
can become swollen and painful. lymphocytes are also generated in 8.12), including plasma cells. Within
Lymph nodes are encapsulated by germinal centres and these are the lymph in the sinuses are
connective tissue (Fig. 8.10). Projecting involved in speedy specific responses immune cells generated in the
inwards from the capsule, at intervals, to subsequent exposure to their cortex and antibodies produced by
are connective tissue trabeculae (septa) ‘remembered’ antigen. plasma cells. Lymph, carrying many
and a fine meshwork of reticulin fibres In the paracortex, lymphocytes are lymphocytes and antibodies, passes
extends throughout each node. Blood able to crawl out of blood in small from the medullary sinuses to the
vessels enter and leave at the hilum of veins and take part in the immune efferent lymphatic vessel and is
each node. Lymph is delivered to each responses occurring in lymph nodes. eventually returned to blood
node by several afferent lymphatic This type of venule is characterised (Chapter 10).
vessels which penetrate the capsule.
Only one efferent vessel drains each
node of lymph and this leaves at the
hilum. Lying within the parenchyma of Cortex
each node are aggregations of lym-
Capsule
phocytes in two main regions, the cortex
and medulla (Fig. 8.10). Connective tissue
Afferent lymphatic Subcapsular sinus
vessel
■ Cortex. Afferent lymph vessels Hilus
deliver lymph into endothelium- Paracortex Efferent lymphatic vessel
lined sinuses which extend around Artery
Medullary cord
each node immediately beneath the
Medullary sinus Vein
capsule (Fig. 8.11). From these
subcapsular sinuses some lymph Valve
continues in endothelium-lined Primary lymphoid follicle
sinuses through the cortex and
medulla and some filters past Secondary lymphoid follicle
lymphocytes in the cortex. Many of
the lymphocytes in the cortex are in
spherical aggregations forming
Fig. 8.10 The internal structure of a lymph node. Arrows show the direction of flow of lymph.
lymphoid follicles which also
contain antigen-presenting cells.
Lymphoid follicles which are
inactive are composed mainly of Subcapsular sinus
small B lymphocytes which stain
densely blue with haematoxylin. If B
lymphocytes are responding to
antigens the follicle has an outer rim
of densely packed, small B
lymphocytes and a central core of
palely stained lymphocytes (Fig.
8.11). Such follicles are described as Lymphocytes in dense rim of follicle
secondary follicles (Fig. 8.10) and the
palely stained region is known as
the germinal centre. New B
lymphocytes are produced by
mitosis in secondary follicles and Palely staining centre of follicle
become activated. Many activated B
lymphocytes appear as medium- or
large-sized lymphocytes and they
have more cytoplasm than small
lymphocytes. The cytoplasm of Connective tissue capsule
activated lymphocytes gives the
palely stained appearance to the
centre of secondary follicles.
Activated B lymphocytes travel to Fig. 8.11 Lymph node, cortex with a secondary lymphoid follicle. Low magnification.
Clinical note
Metastasis This is the
process by which Cord
tumour cells may become
detached and spread from their
original site to distant sites. One
route by which they spread is via
lymphatic vessels. Some tumour
Sinus
cells may enter lymphatic vessels
and pass to lymph nodes draining
the region where the tumour
originated. They may remain in
these lymph nodes and undergo
further rounds of mitosis and
initiate immune responses, and
the nodes may swell. Some
Cord
tumour cells may pass from the
lymph nodes in efferent lymph
and eventually pass around the
body in blood and continue to
proliferate and form metastases
elsewhere. Screening lymph
nodes for tumour cells helps to
assess the spread of tumour cells, Fig. 8.12 Lymph node, medulla with cords and sinuses. Medium magnification.
but once tumours have spread to
lymph nodes such cancers are
much more difficult to cure.
(Tumours may also spread via
veins (and/or directly) into
adjacent tissues.)
Non-encapsulated lymphoid tissue

Clusters of lymphocytes, not surrounded
by a connective tissue capsule, are
present in many regions of the body.
They are particularly important features
of the respiratory, digestive, urinary and
reproductive tracts which are all lined Lymphocytes in primary follicle
by mucosae and vulnerable to foreign
molecules and a variety of organisms.
The clusters may resemble lymphoid
follicles in lymph nodes and are known
as mucosa-associated lymphoid tissue
(MALT). If a cluster is not currently gen-
erating new lymphocytes, it is known as
a primary follicle and is a mass of
densely packed small B lymphocytes
(Fig. 8.13). If lymphocytes in a cluster
are responding to immune stimuli and
generating new lymphocytes they have
a palely stained centre typical of a sec- Blood in vessel
ondary follicle (Fig. 8.11). Fig. 8.13 Tonsil, with a primary lymphoid follicle. Low magnification.
Summary
Blood
■ This comprises red and white blood cells and platelets suspended in plasma.
■ Blood forms tissue fluid (extracellular fluid) and is able to clot and stop flow from damaged blood vessels.
Red blood cells (erythrocytes)

■ These are biconcave discs formed of cytoplasm and a cell membrane (but no nucleus) and are deformable:
■ the cytoplasm consists mainly of haemoglobin, which carries oxygen from the lungs to body tissues
■ red blood cells develop in bone marrow.
White blood cells (leucocytes)

Granulocytes:
■ have nuclei with two or more lobes and cytoplasmic granules

■ develop in bone marrow, circulate in blood and move into tissues
■ are categorised according to the staining characteristics of the granules:
■ neutrophils form 70% of the white cells in blood and phagocytose and kill bacteria
■ eosinophils form about 4% of the white cells in blood and ingest antigen–antibody complexes and kill and ingest parasites
■ basophils form about 1% of the white cells in blood and move into tissue and initiate inflammatory changes.
Agranulocytes:
■ have no (or very few) cytoplasmic granules and are categorised according to nuclear shape
■ lymphocytes have spherical nuclei and form about 25% of white blood cells:
■ B lymphocytes respond to antigens by secreting antibodies and T lymphocytes, respond to ‘foreign’ cells by killing them; NK cells kill
‘foreign’ cells
■ monocytes have indented nuclei and form about 5% of white blood cells
■ migrate from blood and become macrophages in tissues.
Platelets
■ These are small, membrane-bound fragments of cytoplasm that bud off from megakaryocytes in bone marrow. They aid blood clotting.
The immune system

■ The immune system defends the body from foreign molecules, cells and organisms.
■ It comprises a variety of cells (including white blood cells) in the thymus, spleen, lymph nodes and in mucosal surfaces exposed to the
environment.
■ It mounts non-specific responses, e.g. phagocytosis by neutrophils, and specific responses, e.g. the humoral response of B lymphocytes and
the cell-mediated response of T lymphocytes.
■ The immune system also involves mast cells, plasma cells, macrophages and dendritic cells.
Bone marrow
■ This comprises a meshwork of reticulin fibres supporting blood vessels and developing red and white blood cells and megakaryocytes which
form platelets.
Thymus
■ This comprises a meshwork of epithelial cells supporting blood vessels and lymphocytes in an outer cortex densely packed with lymphocytes
and an inner medulla where lymphocytes are less densely packed. Hassall’s corpuscles are present in the medulla.
■ It is particularly active in neonates and regresses with age.
■ Lymphocytes leave the thymus and enter the circulation as mature T lymphocytes which recognise self from non-self cells.
Spleen
■ This comprises a meshwork of reticulin fibres supporting blood vessels, red blood cells and lymphocytes and various antigen-presenting cells.
■ It has red and white pulp regions with sheaths of lymphocytes surrounding arterioles.
■ It monitors blood for foreign material and mounts immune responses and destroys aged red blood cells.
Lymphatic vessels and lymph nodes

■ Lymphatic vessels drain excess tissue fluid and return the fluid as lymph via lymph nodes to blood vessels.
■ Lymph nodes have an outer cortex and inner medulla region and receive lymph from numerous afferent lymph vessels.
■ In the cortex, spherical aggregations (follicles) of lymphocytes are numerous.
■ Lymph percolates through the cortex and lymphocytes may mount immune responses to foreign molecules or cells in lymph.
■ Lymph and cells then pass into the medulla where there are cords of immune cells, which may include plasma cells, and sinuses transporting
the lymph.
■ A single efferent duct drains lymph from the medulla, and eventually all lymph drains into the cardiovascular circulation.
59
Chapter 9
Bone and cartilage
Bone and cartilage are derived from the fibres are capable of deformation under which is composed mainly of fibroblasts
mesoderm layer of the embryo and are stretching forces (and they recoil when (Fig. 9.1). However, there are sites where
specialised forms of connective tissue. the force is reduced). perichondrium is not adjacent to carti-
Together with other connective tissue lage, e.g. on the articulating surfaces of
and skeletal muscle they constitute the bone (Fig. 9.2). Blood capillaries are not
Cartilage
musculoskeletal system. The musculo- present in cartilage and the oxygen and
skeletal system is involved in producing Cartilage has cellular and non-cellular nutrients required by chondrocytes
movement and stability of the body by components. Cartilage cells (chondro- diffuse through the matrix from nearby
transmitting and resisting forces pro- cytes) lie in spaces, known as lacunae, capillaries in the perichondrium.
duced by, for instance, muscle contrac- surrounded by cartilage matrix (the There are three types of cartilage
tion and gravity. Common features of non-cellular component) (Fig. 9.1). The defined by the major type of fibre
bone and cartilage are that they contain matrix is produced by cartilage cells and present:
connective tissue fibres and ground sub- it is a semi-solid material composed of
■ hyaline cartilage contains mainly
stance, forming an extracellular matrix ground substance comprising large mol-
type II collagen fibres and is the
which is relatively rigid compared with ecules (e.g. glycosaminoglycans and pro-
most abundant type of cartilage in
the rest of the body and is able to resist teoglycans), water and connective tissue
the body
mechanical stress. In the extracellular fibres. Cartilage in many regions is sur-
■ elastic cartilage contains type II
matrix, collagen fibres are important rounded by a thin layer of connective
collagen and elastin fibres
in resisting tensile forces and elastin tissue known as the perichondrium,
■ fibrocartilage contains type I collagen
fibres.
Hyaline cartilage
Hyaline cartilage is present in a wide
range of locations and is important in
resisting forces and in supporting soft
tissues. It forms the articulating surfaces
Chondrocyte nucleus of bones in synovial joints (Fig. 9.2),
where it provides a smooth, friction-free
surface at which movements occur, and
it acts as a shock absorber. Hyaline car-
tilage also aids respiration by provid-
ing rigidity in the larynx, trachea and
Extracellular matrix bronchi, thus ensuring their patency
during inspiration (Chapter 11). It is
also present at the anterior ends of ribs
where movements of the rib cage occur
during respiration. In the embryo,
Chondrocyte nucleus hyaline cartilage forms a temporary
skeleton which eventually is largely
replaced by bone (see below).
There are two cell types in hyaline
cartilage: chondroblasts and chondro-
cytes. Chondroblasts are able to undergo
mitosis and secrete extracellular carti-
lage matrix. They are very active meta-
Perichondrium
bolically and may appear in small
clusters. Such clusters (Fig. 9.2) contain
Fig. 9.1 Elastic cartilage and perichondrium, epiglottis. The size of the chondrocytes, and the new cells produced by mitosis from one
lacunae they occupy, varies. Elastin fibres appear as dark strands in the extracellular matrix. Special stain. initial cell in the region. Chondrocytes
High magnification. are the mature form of chondroblasts
degree of deformability and recoil. The

elastin fibres may be readily displayed
Bone marrow using special stains (Fig. 9.1). Elastic car-
tilage is present in, for example, the epi-
glottis and the external ear.
Bone Fibrocartilage
Fibrocartilage is present in the second-
ary cartilaginous joints of the body, e.g.
Hyaline cartilage (of growth plate) in intervertebral discs (Fig. 9.3). Fibrocar-
tilage is not invested by perichondrium
and in general it is less rigid than hyaline
cartilage. The chondrocytes in fibrocar-
tilage often appear oriented along the
Region of large chondrocytes
lines of stress on the cartilage and there
are intervening layers of collagen fibres
Cluster of small chondrocytes (type I). Fibrocartilage provides resist-
ance to mechanical forces and some-
times is also present in the dense, regular
connective tissue in tendons and
Hyaline cartilage
ligaments.
Bone
Bone plays a vital physical role in pro-
tecting delicate underlying body struc-
Cluster of small chondrocytes
tures, e.g. the heart and brain. Collect-
ively, bones form the jointed skeleton of
the body and, in conjunction with the
attachment sites of skeletal muscles and
Articular surface
tendons, bones act as levers and enable
movements to occur. Although bone is
Fig. 9.2 Hyaline cartilage of an articular surface of bone from a synovial joint. Medium hard and apparently inert, it is able to
magnification.
remodel in response to changes, e.g. in
the stresses acting upon it, particularly
and are no longer able to undergo increasingly larger regions between the during growth, exercise and after frac-
mitosis but can still secrete and modify cells. Appositional growth occurs at the ture. In addition, calcium in bone acts as
cartilage matrix. The main chemical periphery of clusters of cartilage cells, a store for use by the rest of the body if
components of hyaline cartilage matrix adjacent to the perichondrium. Fibro- calcium uptake in the diet is inadequate.
are proteoglycans, glycosaminoglycans blasts in the innermost part of the peri- Bone also provides the framework for
and hyaluronic acid, which all attract chondrium are specialised and known body shape (along with fat and muscle)
water molecules. This composition as chondrogenic cells as they can become and spaces in bones, filled with bone
allows hyaline cartilage to resist com- chondroblasts and secrete cartilage marrow, are sites where blood cell
pressive forces and act as a shock matrix. Most cartilage in the body grows formation (haematopoiesis) occurs
absorber. The type of collagen fibres by appositional growth. However, there (Chapter 8).
(type II) and their orientation in hyaline are exceptions. For example, articular Bone consists of several types of bone
cartilage are important in resisting cartilage is not invested by perichon- cell and associated bone matrix. Most
mechanical forces. The appearance of drium (Fig. 9.2) and grows only by bone cells in adults are osteocytes and
hyaline cartilage is described as ‘glassy’ interstitial growth. Furthermore, growth they lie in lacunae embedded in extra-
and the collagen fibres are not apparent of long bones, which occurs up to cellular bone matrix. Although bone
in routine histological preparations. the age of about 20 years, also occurs matrix resembles cartilage matrix (Fig.
With age, chondrocytes and the lacunae via interstitial growth of cartilage (see 9.4) it has organic and inorganic compo-
they occupy enlarge (Fig. 9.2) and below). nents. The organic components of bone
calcium salts may be deposited in the matrix include type I collagen fibres,
matrix. These changes may alter the Elastic cartilage proteoglycans and glycosaminoglycans.
mechanical properties of the cartilage. There are similarities between the struc- The inorganic component of bone
Growth in hyaline cartilage occurs by ture and mode of growth of hyaline and matrix consists largely of calcium
two modes: interstitial and appositional elastic cartilage. However, chondrocytes hydroxyapatite (Ca10(PO4)6(OH)2). The
growth. Interstitial growth (growth from in elastic cartilage are larger than those hydroxyapatite is deposited alongside
within) occurs mainly in the early stage in hyaline cartilage and the volume of the collagen fibres and this produces the
of cartilage development. In interstitial matrix is less. The matrix of elastic carti- rigid hardness of bone. In comparison
growth, cartilage cells in lacunae undergo lage contains type II collagen fibres, but with cartilage matrix, the composition
mitosis, produce matrix and separate in addition it has an abundance of elastin of bone matrix restricts the diffusion of
from one another; the matrix occupies fibres which confers on the cartilage a gases, nutrients and waste molecules.
Bone and cartilage 61
However, bone matrix is permeated

by small blood vessels (capillaries),
an arrangement that ensures osteocytes
receive sufficient oxygen and nutrients.
Individual bones are covered by a thin
Fibrocartilage layer of connective tissue (the perios-
teum) except at some joint surfaces, e.g.
in synovial joints the ends of the bones
are covered by hyaline cartilage (Fig.
9.2). Periosteum contains collagen fibres,
small blood vessels and fibroblasts,
which can differentiate and become
bone-forming cells. Importantly, colla-
gen fibres surrounding many skeletal
muscle cells and those in tendons and
ligaments are anchored to periosteum
and pass through into the bone matrix
as Sharpey’s fibres. Such collagen fibres
transfer forces from muscles, tendons
and ligaments to bones.
There are four major cell types in
bone: osteoprogenitor cells, osteoblasts,
osteocytes and osteoclasts.
Hyaline cartilage ■ Osteoprogenitor cells are fibroblast-

like cells in the inner layer of the
periosteum adjacent to the surface of
bone: they function as stem cells. In
Fig. 9.3 Intervertebral disc. Fibrocartilage and hyaline cartilage. Special stain. Medium magnification.
actively growing bone or after
fracture they undergo mitosis. Some
offspring cells differentiate into
osteoblasts whilst others remain as
osteoprogenitor cells.
■ Osteoblasts (Fig. 9.5) are present at
the surface of bone matrix (and the
surface of hyaline cartilage matrix in
growing bones; see below). Their
appearance depends on their level of
Lacuna with chondrocyte activity in synthesising new matrix:
inactive osteoblasts have little
cytoplasm but active ones may
Hyaline cartilage matrix
appear polygonal or cuboidal in
Lacunae with osteocytes shape. Active osteoblasts have an
abundance of rough endoplasmic
reticulum in their cytoplasm,
reflecting their activity in secreting
the organic components of bone
Bone matrix
matrix. Newly formed bone matrix,
deposited onto the surface of
existing matrix, does not contain
calcium salts and is known as
osteoid. Rapidly, osteoid becomes
mineralised by the addition of
Space occupied by blood vessels
(in life) calcium salts and this forms bone
matrix. Osteoblasts are essential in
this calcification process, which
confers rigidity on bone.
Fig. 9.4 Bone and hyaline cartilage. Only the nuclei of osteocytes and chondrocytes are apparent In contrast to the growth of
(in their lacunae) at this magnification. In some regions, the regular arrangement of bone matrix helps cartilage, bone growth occurs only
distinguish it from the smooth ‘glassy’ appearance of hyaline cartilage matrix. Low magnification.
by the appositional method of
adding matrix onto the surface of
existing matrix. Once osteoblasts are
surrounded by bone matrix they
become osteocytes and do not
undergo mitosis; thus, interstitial

growth does not occur.
■ Osteocytes are mature bone cells and
Osteoblast nuclei they are located in lacunae
surrounded by bone matrix (Figs 9.4
and 9.5). They are relatively inactive
Osteocyte nucleus cells. Long cytoplasmic processes
extend from osteocytes and pass in
channels (canaliculi) in bone matrix
Red blood cells in vessel (Fig. 9.6). Through these cytoplasmic
processes osteocytes are able to
exchange gases and molecules with
Bone matrix
blood in nearby capillaries in bone
Osteogenic cells and osteoblasts matrix (see below). Osteocytes are
involved in metabolic processes
Developing bone marrow which help maintain bone matrix.
Periosteum ■ Osteoclasts are involved in the
remodelling of bone such as that
occurring during growth,
development and fracture repair.
Unlike other bone cells which are
derived from fibroblast-like cells,
osteoclasts are derived from blood
monocytes. Osteoclasts are large,
Fig. 9.5 Bone and periosteum. The cells on the surface of bone adjacent to the periosteum include
osteogenic cells and osteoblasts but distinguishing them at this magnification is not possible. Medium multinucleated cells (Fig. 9.7) and
magnification. they lie on the surface of bone
matrix, sometimes occupying small
depressions known as Howship’s
lacunae. Osteoclasts secrete enzymes
onto the bone matrix that digest the
matrix releasing ions and small
molecules, e.g. calcium and
phosphate ions and amino acids.
The released small molecules enter
blood vessels, circulate and are
available for use elsewhere in the
body.
The activity of osteoclasts is under
the control of two hormones
(Chapter 14) that ensure circulating
Osteocyte nuclei
blood levels of calcium are regulated.
Parathyroid hormone stimulates
osteoclasts to resorb bone and this
Haversian canal raises blood calcium. Osteoclast
activity is inhibited by calcitonin
from the parafollicular cells of the
thyroid gland and this lowers blood
Concentric lamellae calcium.
Types of bone
Most bones in the body contain compact
(dense) and cancellous (spongy) bone.
Compact bone is very dense compared
with cancellous bone (Fig. 9.8). In a
typical adult long bone, e.g. the humerus,
compact bone forms an outer collar
Fig. 9.6 Compact bone, transverse section of an osteon showing a Haversian canal. The along the shaft (diaphysis), whereas can-
canaliculi (spaces occupied by cytoplasmic processes of osteocytes) appear as very fine dark strands cellous bone constitutes the less dense
radiating from the Haversian canal to osteocytes. Only the nuclei of osteocytes are clearly seen. Special interior. Cancellous bone forms most of
stain. High magnification.
the ends of long bones (the epiphyses)
in adults although compact bone may
form a thin rim. (Hyaline cartilage is
also a component of epiphyses of bones
involved in synovial joints and it covers
the joint surface.) Spaces within cancel-

lous bone (Fig. 9.8) are filled by bone
Bone marrow marrow, which is involved in blood cell
formation, and fat cells; the number of
fat cells increases with age.
Compact bone is based on an arrange-
ment of bone cells and matrix known as
Osteoclast the Haversian system. This arrangement
consists of many thin layers (lamellae)
of bone (Fig. 9.6) arranged concentri-
cally as cylinders which lie along the
length of the shaft of long bones. This
arrangement gives maximal resistance
Bone matrix to forces acting along the bone and is
particularly important in resisting com-
Osteocyte nucleus pression due to weight bearing. Osteo-
cytes, in lacunae, are embedded within
Fig. 9.7 Osteoclast. High magnification. the lamellae and lie in concentric circles
which are apparent if the cylinders are
sectioned across their length, i.e. trans-
versely (Figs 9.6 and 9.9). At the centre
of each cylinder of lamellae are small
blood and lymphatic vessels and nerves
in a space known as a Haversian canal
(Figs 9.6 and 9.9). Cytoplasmic processes
of osteocytes extend through very small
channels (canaliculi) in the bone matrix
(Fig. 9.6) and via this route exchange
gases and molecules with blood in
vessels in a nearby Haversian canal. The
whole unit of a Haversian canal plus
lamellae is known as an osteon. Although
Haversian systems have such a highly
regular arrangement of osteons, in many
regions the cylinders are packed together
with irregular lamellae of bone (Fig. 9.9).
The regularity of the cylinders of osteons
Cancellous bone is also apparent when they are sectioned
along their length (Fig. 9.10). In addi-
tion, canals (Volkmann’s) carry vessels
and nerves perpendicular to Haversian
canals. The presence of blood vessels in
Periosteum bone matrix ensures all osteocytes have
adequate oxygen and nutrients, without
which they die and the bone matrix
degenerates.
Cancellous bone consists of thin spi-
Bone marrow
cules (trabeculae) of bone that project as
a meshwork from compact bone (Fig.
Cancellous bone 9.8). This type of bone has a random
lamellar structure with osteocytes
Compact bone located in lacunae but it does not have
Haversian or Volkmann’s canals. The
osteocytes are nourished via diffusion
from blood vessels in the marrow.
Fig. 9.8 Compact and cancellous bone and bone marrow. Low magnification. Bone formation and growth
Bone formation (ossification) and
growth of bones begins in utero and
continues up to the age of 20 or so. After
this time, ossification and bone growth
stops but the components of matrix
are gradually removed and/or replaced
throughout life. In addition, at any stage,
Fig. 9.9 Compact bone, transverse section of

osteons showing their Haversian
canals. Nuclei of osteocytes appear as small dark
dots; some lie in concentric circles formed by
lamellae of bone. A black line surrounds some
Concentric lamellae in osteon irregularly placed lamellae. Special stain. Medium
magnification.
Haversian canals
Irregularly placed lamellae
Fig. 9.10 Compact bone, longitudinal section

of osteons. Nuclei of osteocytes appear as small
dark dots in rows formed by lamellae of bone.
Special stain. Medium magnification.
Volkmann’s canal
Haversian canals
Volkmann’s canal
the shape of bones may be remodelled skull. In regions where these bones Endochondral ossification
in response to various factors including develop, some fibroblast-like cells (osteo- The majority of bones in the skeletal
dietary changes, strenuous exercise or progenitor cells) derived from meso- system are formed, and grow, by endo-
physical damage. Bone formation derm of the embryo differentiate into chondral ossification. In this process a
and growth occurs by two methods: osteoblasts which then secrete an irreg- ‘model’ of hyaline cartilage, comprising
intramembranous and endochondral ular framework of bone matrix. Growth chondrocytes and cartilage matrix in the
ossification. occurs as further fibroblast-like cells shape of the adult bone, develops first
on the surface of the developing bone (Fig. 9.11). The cartilage model grows
Intramembranous ossification differentiate and become osteoblasts and gradually bone matrix and bone
This type of bone formation and growth which then add bone matrix onto the cells replace the cartilage in the diaphy-
is associated only with flat bones, such existing matrix, i.e. by appositional sis. In growing long bones the diaphysis
as the clavicle and some bones in the growth. is separated from each epiphysis by an
epiphyseal growth plate (EGP) of carti-

lage. This is the region where many
bones grow in length until adulthood.
There are several stages in endochon-
dral ossification.
Chondrocytes in epiphysis
1. Hyaline cartilage model forms (Fig.
9.11).
■ Some bones (e.g. the femur) begin Perichondrium
to form in utero at about 6 weeks
(in humans).
■ Appositional and interstitial
growth occurs in the cartilage
model and shape develops.
■ Chondrocytes in the centre of the Chondrocytes in diaphysis
model increase in size.
■ Calcium salts are deposited in the
Perichondrium
matrix around the older
chondrocytes, which eventually die
(see below).
2. Collar of bone forms (Fig. 9.12).
■ Osteogenic cells and blood vessels
develop in the perichondrium.
■ The osteogenic cells become
osteoblasts which form a collar of
bone (bone cells and matrix) around
the diaphysis. This is described as a
primary ossification centre.
Joint cavity
■ The perichondrium in the region
of the bone becomes periosteum.
3. Invasion of the bone collar occurs
(Fig. 9.13). Fig. 9.11 Hyaline cartilage model of a developing bone sectioned along its length. Low
■ Cells in the periosteum invade the magnification.
collar of bone forming a
‘periosteal bud’.
■ The invasion brings osteogenic
cells (and cells which form red
and white blood cells and blood
vessels) into the diaphysis. Chondrocytes (small) in epiphysis
4. The large old chondrocytes die and
disappear; bone and bone marrow
form (Figs 9.13 and 9.14).
■ Chondrocytes die and leave a
loose meshwork of cartilage
matrix.
■ The invading cells from the
periosteal bud enter the spaces
left in old, calcified cartilage
matrix.
Chondrocytes (large) in diaphysis
■ Osteoblasts (developed from the
invading osteogenic cells) secrete
bone matrix onto the calcified Bone matrix
cartilage matrix.
Periosteum
■ Osteoblasts surrounded by bone
matrix become osteocytes (Fig.
9.15).
■ Bone marrow forms from the
invading cells as red and white Cartilage matrix
blood cells and blood vessels
develop.
5. Ossification extends. Perichondrium
■ Osteoblasts continue to deposit Fig. 9.12 Bone collar around diaphysis of a developing bone (sectioned along its length). The
bone matrix onto cartilage matrix osteocytes in the bone matrix can be distinguished by their nuclei which appear as small dots in the
at each end of the diaphysis. pink-stained matrix. Medium magnification.
■ Chondrocytes remain as an EGP

(Fig. 9.16) at each end of a diaphysis
for several years. Chondrocytes
produced by mitosis in these plates
Chondrocytes in large lacunae
are responsible for the growth in
Cartilage matrix (no apparent length of bones until adulthood.
chondrocytes)
Bone collar Growth in length of bone at

epiphyseal plates
Periosteum EGPs have several zones involved in
ensuring each diaphysis grows in length.
Red blood cells in vessel Each zone merges with adjacent zones
invading the bone collar
(Fig. 9.15 and 9.16).
Fig. 9.13 Invasion of bone collar (sectioned across the length of the bone). The invasion ■ Zone of reserve cartilage. This is the
involves blood in vessels, osteogenic cells and stem cells capable of forming blood cells. Only red cells hyaline cartilage connecting each
can be distinguished in this micrograph. Medium magnification. EGP to the adjacent epiphysis.
■ Zone of proliferation. Chondrocytes
proliferate rapidly and new
chondrocytes extend as columns of
cells parallel to the long axis of the
bone and away from the epiphysis.
This is interstitial growth. Older
chondrocytes in the columns, those
farthest from the reserve zone, begin
to secrete cartilage matrix. By
forming these new cells and matrix
Perichondrium in columns, the length of the
diaphysis is extended and a
framework is formed on which bone
is later deposited.
■ Zone of hypertrophy. With increasing
age chondrocytes enlarge.
■ Zone of calcification and chondrocyte
death. Calcium salts are deposited in
Periosteum the cartilage matrix and the oldest
chondrocytes die, probably due to
Bone collar programmed cell death (apoptosis).
■ Zone of ossification. Osteoprogenitor
Old cartilage matrix cells migrate from the diaphysis and
become osteoblasts as they secrete
bone matrix onto the surface of the
calcified cartilage matrix. This
Developing marrow and blood process extends the length of the
vessels
bone of the diaphysis. Calcium salts
are then deposited into the bone
Chondrocyte (large, old) matrix and some osteoblasts become
surrounded by bone matrix and
become osteocytes (Fig. 9.15).
Growth in width of bone

Circumferential growth of each diaphy-
Chondrocytes in epiphysis
sis occurs as osteoprogenitor cells in the
periosteum become osteoblasts and lay
bone matrix on the outer surface of the
Fig. 9.14 Chondrocyte loss, bone and bone marrow formation. Chondrocytes have died and shaft (appositional growth). At the same
disappeared from the centre of the diaphysis and only a few remnants of cartilage matrix remain there.
Low magnification.
time osteoclasts remove bone from the
inner surface of the shaft. As a result
the width of the outer rim of compact
bone is adjusted and does not become
thicker as the overall width of the bone
increases. Gradually, the adult distribu-
tion of cancellous and dense bone
develops.
Bone marrow
Osteocytes in bone
matrix
‘Old’ cartilage matrix
Oldest chondrocytes
Hyaline cartilage of epiphyseal

growth plate
Hyaline cartilage of epiphysis
Fig. 9.15 Epiphyseal growth plate. See text for details of the processes occurring in growth plates. Special stain. Medium magnification.
Articular cartilage Remodelling of bone

There is considerable remodelling of the
Epiphysis
shaft of long bones through resorption
Bone matrix
of matrix and deposition of new bone
Blood vessel at site starting matrix. The regions where bone matrix
secondary ossification
is initially deposited on cartilage matrix
Perichondrium Zone of reserve cartilage are digested by osteoclasts at the same
Epiphyseal growth plate time as new bone is added to existing
bone matrix.
Compact bone of diaphysis
Spongy bone of diaphysis
Growth of epiphyses and cessation
Periosteum Bone marrow and blood vessels
of growth
Blood vessel at site of Interstitial growth of cartilage, and appo-
primary ossification sitional growth (in regions adjacent to
Old cartilage matrix perichondrium), increases the volume
Epiphyseal growth plate
(see text for zones) of each epiphysis. Just after birth, small
regions develop where blood vessels
and osteogenic cells invade some epi-
physes, a process described as secondary
ossification (Fig. 9.16). Gradually, over
the next 20 years or so, bone and bone
marrow replace the hyaline cartilage of
Fig. 9.16 A typical growing long bone. Epiphyseal growth plates are present at each end of the epiphyses, except at surfaces involved in
diaphysis. In one epiphysis a secondary ossification centre has started to replace the hyaline cartilage synovial joints where hyaline cartilage
with bone. remains.
Epiphyses fuse with their diaphysis
as bone replaces the hyaline cartilage of
the growth plates. The time at which
this ossification occurs differs between
different bones in the body. These
times are relatively constant between
individuals.
Clinical notes
Osteoporosis This condition results from a decreased level of calcium in bones. Age-related loss of bone
mineral density occurs in all persons to an extent. In women especially, there is increased activity of
osteoclasts after the menopause as oestrogen levels decrease due to the loss of secretion of these hormones from the
ovaries. The affected bones are often fractured with minimal force. Oestrogen therapy, and high intake of calcium,
helps to slow the disease progression.
Genetic disorders These may affect epiphyseal growth plates and result in individuals shorter or taller than
normal. (Epiphyseal growth plates and adult height may also be abnormal as a result of abnormal levels of growth
hormone secreted by the pituitary gland.)
Osteoarthritis and rheumatoid arthritis These inflammatory processes that occur in cartilage are common.
Osteoarthritis affects the hyaline cartilage covering the ends of articulating bones, particularly affecting weight-bearing
joints such as knees, hips and ankles. In this disease the cartilage slowly degenerates with age, with underlying
damage affecting the bone. In contrast, rheumatoid arthritis is a systemic autoimmune disease that affects other
organs and tissues as well as joints. Because of its widespread effects, rheumatoid arthritis is much more difficult to
treat. Rheumatoid arthritis, in contrast to osteoarthritis, may affect young people and may pursue a much more
aggressive course.
Summary
Bone and cartilage
■ These are connective tissues with relatively rigid extracellular matrix containing collagen fibres and large molecules containing carbohydrates.
Bone is more rigid than cartilage and has extensive deposits of calcium salts in the extracellular matrix.
■ Mature cartilage and bone cells (respectively, chondrocytes and osteocytes) occupy spaces (lacunae) in the matrix.
■ Osteocytes in many regions are nourished by a network of capillaries in Haversian canals.
Cartilage
■ This occurs in three types:
■ hyaline cartilage forms the smooth articulating surfaces of many bones and has a major role in skeletal development
■ elastic cartilage has a matrix containing elastin and collagen and is able to recoil after being deformed
■ fibrous cartilage provides resistance to mechanical forces.
■ Cartilage grows by appositional and interstitial growth.
Bone
■ Bone protects many organs and provides firm attachments for muscles and tendons which allows movements to occur.
■ It may be described as compact (dense) or cancellous (spongy):
■ in compact bone the matrix comprises cylinders of lamellae of bone around blood vessels in a Haversian canal
■ in cancellous bone thin trabeculae of bone matrix form a meshwork.
■ It begins to develop in utero as a hyaline cartilage model and becomes bone by endochondral ossification. (A few bones form directly by
intramembranous ossification.)
■ In endochondral ossification the hyaline cartilage model grows by interstitial and appositional growth.
■ The cartilage is replaced as chondrocytes die and osteogenic cells become osteoblasts which deposit bone matrix on old cartilage matrix.
■ Up to about 20 years of age cartilage persists in some bones as an epiphyseal growth plate (EGP) between the diaphysis and an epiphysis.
Growth in the length of bones is a result of cartilage cells proliferating in EGPs and bone matrix being deposited on old cartilage matrix.
■ Osteoclasts digest bone and are involved in remodelling during growth, development and repair.
69
Chapter 10
The circulatory system
The circulatory system consists of the 12). Lymph eventually drains into larger deoxygenated blood to the right side of
heart and the vessels (tubes) which carry lymph vessels which in turn drain into the heart, which pumps it into pulmo-
blood or lymph. The heart provides a the blood vessels of the cardiovascular nary arteries and on to the lungs. In the
force that moves blood in the vessels of system returning blood to the heart. lungs, the deoxygenated blood passes
the cardiovascular system. This part of into capillaries and there it becomes
the circulatory system, the cardiovas- oxygenated. The oxygenated blood
Cardiovascular system
cular system, ensures blood, carrying returns to the left side of the heart via
oxygen, carbon dioxide, various nutri- The heart is an organ which consists of pulmonary veins. This flow of blood
ents, metabolites, hormones and blood two muscular pumps that work in syn- between heart and lungs is known as
cells, is conveyed to, through and from chrony. The two pumps are attached the pulmonary circulation. Simultane-
the tissues and organs of the body. side by side but blood, in adults, does ously, the left side of the heart pumps
Part of the circulatory system com- not pass directly between the two sides. oxygenated blood into the aorta (the
prises lymphatic vessels which drain The heart develops (in utero) from a largest artery) from where it is distrib-
some of the extracellular fluid from all single tube which duplicates and twists uted around the whole body. Arterial
regions of the body except the central and only takes on the adult structure blood passes through progressively
nervous system. The fluid in lymphatic and the physical separation of the two branching and narrowing arterial vessels
vessels is known as lymph. It is similar sides shortly after birth (see Mitchell B, and eventually through the narrowest
to plasma but does not transport red Sharma R. Embryology: An Illustrated vessels, the capillaries. It is from capillar-
cells. Lymph is an important means of Colour Text. Elsevier: 2004). ies that oxygen diffuses into surround-
transporting immune cells, particularly Arteries are vessels which carry blood ing tissues and blood becomes
lymphocytes, and lymph vessels carry away from the heart whilst vessels car- deoxygenated. Capillaries drain into
lymph into and out of lymph nodes rying blood to the heart are veins (Fig. venules and these in turn drain into
(Chapter 8). Lymphatic vessels in the 10.1). Blood is carried between arteries veins which return the deoxygenated
gastrointestinal system also transport and veins in small vessels, arterioles, blood to the right side of the heart. This
lipids absorbed from the gut (Chapter capillaries and venules. Veins deliver flow of blood around the body is
described as the systemic circulation.
In some regions of the body, e.g. the
Pulmonary Pulmonary Aorta Pulmonary liver (Fig. 10.1), in addition to arterial
veins artery veins blood delivering oxygenated blood to
capillaries, other blood enters the capil-
Right lung Left lung laries from a vein. In the case of the liver,
capillaries draining blood from the gut
join together and drain into the hepatic
portal vein. This portal vein, carrying
LA nutrients absorbed from the gut, sup-
RA
plies blood to capillaries in the liver.
LV This arrangement of vessels involving
RV two sets of capillaries joined by a vein is
Capillary bed in Capillary bed in described as a portal circulation.
circulation to right lung circulation to left lung
(pulmonary circulation) Liver (pulmonary circulation)
Heart
Capillary bed in liver Each side of the heart has two compart-
Hepatic vein
Artery to liver Portal ments: an atrium and a ventricle (Fig.
circulation
Vein from gut to liver 10.2). The left atrium receives blood
(hepatic portal vein) from the lungs in four pulmonary veins
RA = Right atrium and the right atrium receives blood
LA = Left atrium Capillary bed in
RV = Right ventricle circulation to body from the rest of the body via the
LV = Left ventricle (systemic circulation) superior and inferior vena cavea. The
Fig. 10.1 The cardiovascular components (heart and the systemic, pulmonary and portal atria simultaneously contract and pump
circulations) of the circulatory system. Arrows indicate the direction of flow of oxygenated blood blood into the paired ventricles. The
(red) and deoxygenated blood (blue). ventricles then pump the blood into
Superior either the systemic circulation (left ven-

vena cava tricle) or the pulmonary circulation
Arch of aorta (right ventricle). Valves between each
atrium and its ventricle ensure that
Right
pulmonary blood does not flow back into the atria
Left pulmonary
artery to artery to left lung when the ventricles contract. Other
right lung valves prevent back flow of blood from
the arteries to the ventricles when the
Blood from lungs ventricles relax. The contraction of heart
Aortic valve LA (2 of 4 pulmonary veins) muscle is regulated by the autonomic
nervous system, though heart muscle
Pulmonary Fibrous pericardium
valve cells have an intrinsic ability to
RA Parietal layer of contract.
serous pericardium
The wall of the heart is described as
Visceral layer of having three layers: the myocardium is
serous pericardium
the middle and thickest layer, the inner
Pericardial cavity layer is the endocardium and the outer
LV
Inferior layer is the epicardium. In addition,
vena cava
RV connective tissue is an important com-
RA = Right atrium
RV = Right ventricle ponent which ensures normal heart
Myocardium LA = Left atrium contraction occurs.
LV = Left ventricle
V = Atrioventricular valves ■ Myocardium. The myocardium
Fig. 10.2 The internal structure of the heart, the major blood vessels and the forms the majority of the wall of the
pericardium. Arrows indicate the direction of flow of blood. V, valves between atria and ventricles. heart: it consists mainly of cardiac
muscle cells supported by sparse,
fibrous connective tissue. If these
muscle cells are sectioned along
their length, transverse striations are
apparent (Fig. 10.3), reflecting the
arrangement of myofilaments in the
sarcoplasm of the cells (Chapter 5).
Specialised junctions (intercalated
discs) attach cells together in series
and may be apparent as transverse
lines (Fig. 10.3). Although heart
muscle cells have an intrinsic ability
to contract, sympathetic and
parasympathetic nerves are able,
Purkinje cell nucleus respectively, to increase and decrease
the rate at which the heart beats.
The contraction of cardiac muscle
cells is coordinated by specialised
Intercalated discs cells in several regions of the heart
and by communication, via
intercalated discs, between individual
muscle cells. One specialised cell
Purkinje cell cytoplasm type, the Purkinje cell, conducts
electrical impulses to specific parts
of the myocardium so that atria and
ventricles contract at appropriate
times and blood flows smoothly
from atria to ventricles then into
the arteries. Purkinje cells are
distinguished by their rounded
shape (Fig. 10.3) and they have a
high content of glycogen.
■ Endocardium. This lines the
myocardium. It is made up of a
surface layer of squamous epithelial
Fig. 10.3 Heart myocardium with cardiac muscle and Purkinje cells. Transverse striations are
cells, their basement membrane and
apparent in cardiac muscle cells sectioned along their length as lighter and darker regions of pink-
stained sarcoplasm. Intercalated discs appear as darker, wider, pink-stained bands. The glycogen a sparse layer of connective tissue
packing the cytoplasm of Purkinje cells is palely stained as glycogen does not react well with the stain attaching the endocardium to the
used. Connective tissue is stained green. Special stain. High magnification. myocardium. The epithelial cells of
The circulatory system 71
the endocardium are similar to, and

continuous with, the endothelial Lumen
cells lining the blood vessels carrying
blood to and from the heart.
■ Epicardium. The epicardium covers
the heart and comprises a single
layer of squamous epithelial cells,
Elastin in wall of aorta
their basement membrane and loose
connective tissue which attaches it to
the underlying myocardium.
Coronary blood vessels supply blood
to the heart and lie in the
epicardium, in which fat cells may
be present in large numbers (Fig.
10.4).
The epicardium is part of a closed sac, Valve

the pericardium, which enfolds the
heart (Fig. 10.2). It is the inner, visceral
layer of the pericardium and is continu-
ous with the outer parietal layer. Each
of these two layers is composed of a
squamous epithelium, basement mem-
brane and supporting connective tissue
and they enclose a potential space, the Epicardium
pericardial cavity. The secretion of
minute amounts of fluid into the peri-
cardial cavity by the lining of squamous
epithelial cells ensures a relatively fric-
tion-free zone against which the heart
can move and beat without damaging
adjacent cells.
Connective tissue of the heart Myocardium of ventricle

Some connective tissue of the heart is Fig. 10.4 Part of heart wall, a valve and a blood vessel. An arrow indicates the direction of flow
condensed and described as a fibrous of blood from a ventricle to the blood vessel. The epicardium covering this myocardium appears empty
skeleton. It is a complex arrangement of as lipid has been extracted from the adipocytes in the epicardium. (The surface epithelial cells of the
dense collagen between the atria and epicardium are not resolved at this magnification.) A valve projects into the vessel and is attached to
the connective tissue surrounding the myocardium. Elastin, stained brown, in the wall of the blood
ventricles, and around the orifices of the
vessel indicates it is an artery (it is sectioned along its length and only one part of the wall is present).
arteries taking blood from the heart (Fig. Collagen is stained blue/green. Special stain. Very low magnification.
10.4). The connective tissue ensures
electrical discontinuity between the
myocardium of the atria and ventricles
except via the specialised conducting Clinical notes
tissue; this is essential for the normal Angina This is caused by a slow, but progressive, reduction in
rhythm of heart contraction. In addition, the luminal diameter of the coronary arteries that supply blood
the connective tissue anchors the cardiac to the heart and is usually due to the accumulation of fatty material in the
muscle cells and is the major compo- walls of these arteries. This process, atheroma formation, may begin as early
nent of, and anchor for, the valves (Figs as 21 years of age as a result of Western-style diets. Angina is manifested by
10.3 and 10.4). characteristic pain which spreads across the chest wall after exercise. The
pain is perceived when insufficient oxygen reaches the cardiac muscle cells
Blood vessels and they are unable to sustain the increased rate of contraction needed for
Blood is pumped away from the heart the exercise.
into arteries which branch and distrib- Myocardial infarction This is the term used to describe the pathological
ute blood, under relatively high pres- process of complete or incomplete obstruction of the coronary arteries
sure, to all regions of the body. Arterial supplying the heart. The blockage may be due to the deposition of fatty
blood passes into smaller arteries (arte- material in the wall of a coronary artery or the presence of a blood clot
rioles) and then into very small vessels blocking a coronary artery. Once the blood supply, and therefore oxygen
(capillaries) which have very thin walls supply, to the cardiac muscle cells is reduced or cut off, the cells die and the
(one cell thick). Capillaries are described patient suffers what is often referred to as a heart attack. If the attack is not
as exchange vessels because molecules, fatal the heart may be weakened. The dead muscle cells are not replaced by
including carbon dioxide and oxygen, new muscle cells and connective tissue forms a scar. The normal pattern of
move into and out of capillaries across heart muscle contraction may be compromised as a result.
concentration gradients. In addition,
some of the components of plasma

leave capillaries and form extracellular Tunica adventitia
(tissue) fluid. Some excess tissue fluid
returns to small veins (venules) whereas
other fluid drains to lymph capillaries
(see below). The rate at which extra-
cellular fluid is formed from plasma
normally equals the rate at which fluid
drains back into blood and lymph
vessels. Blood in capillaries, under rela- Tunica media
tively low pressure, passes into venules
which join and form veins. In turn, veins
join together and return blood to the
heart. In several regions of the body,
some arterial blood bypasses capillaries
and passes into venules in what are
described as arteriovenous shunts. In
the skin, such a route reduces heat loss
and thus aids thermoregulation.
The walls of arteries and veins are
Lumen of aorta
similar in that they are made up of three
layers but the layers vary in structure
according to the function of the vessels.
In some veins the boundary between
Fig. 10.5 Part of the wall of a conducting artery (the aorta) sectioned across its length. Elastin
the layers is not clearly defined. The
fibres (stained brown) form sheets in the tunica media which are wrapped around the lumen of
layers are: conducting arteries; in transverse sections, they appear as thin, wavy strands. (The inner tunica intima is
so thin it cannot be distinguished at this magnification.) Collagen fibres (stained red) show part of the
■ Tunica intima. This is the very thin tunica adventitia. Special stain. Low magnification.
inner layer which lines all arteries
and veins and which is composed of
endothelium (i.e. a simple squamous
epithelium) and its basement
membrane and a small amount of
underlying loose connective tissue.
In many vessels the endothelial cells
are attached firmly to each other by
tight junctions (Chapter 2).
■ Tunica media. This is the middle layer
and it forms the largest proportion of Tunica adventitia
the wall of many arteries and veins.
Smooth muscle cells and the
connective tissue fibre elastin may be
predominant in this layer. In general,
arteries closest to the heart have most
elastin in this layer and some vessels
Tunica media
have numerous sheets (laminae) of
elastin (Figs 10.4 and 10.5). Arteries
further from the heart have more
smooth muscle than elastin in this
layer (Fig. 10.6). Some veins have Internal elastin lamina
smooth muscle in the tunica media,
but generally they have fewer smooth
muscle cells in their walls than Lumen of artery
arteries.
■ Tunica adventitia. This is the outer
layer, surrounding the tunica media,
and it is usually composed of
collagenous connective tissue (Fig.
10.5). It is an indistinct layer and it
merges with adjacent connective
tissue fascia (the packing tissue of
Fig. 10.6 Part of the wall of a distributing artery. Elastin fibres are stained brown. The tunica
the body) and thus holds vessels in media and the tunica adventitia can be clearly distinguished but the tunica intima, which is separated
place. In some vessels elastin fibres from the tunica media by the internal elastin lamina, is so thin it cannot be distinguished at this
are present in this layer (Fig. 10.6). magnification. Special stain. Low magnification.
Blood vessels (and nerves supplying

smooth muscle cells in the tunica
media) pass though the tunica
adventitia.
In addition to the three tunicae, an

internal elastin lamina may be present
between the tunica intima and tunica
media (Fig. 10.6) and an external elastin
lamina between the tunica media and
the tunica adventitia. Red blood cells in lumen of
arteriole
Arteries
Arteries may be classed as conducting Smooth muscle cell nucleus
or distributing arteries or as arterioles.
■ Conducting arteries are the largest

arteries, closest to the heart and they
contain a high proportion of elastin
in their walls with few smooth
Endothelial cell nuclei
muscle cells. They include the aorta
(Fig. 10.5), which receives blood
from the left ventricle of the heart.
The elastin is arranged as multiple
sheets around the vessels which
allow conducting arteries to distend
each time the heart contracts and Fig. 10.7 Arteriole sectioned across its length. Nuclei of smooth muscle cells in the wall of this
arteriole appear long and narrow and their cytoplasm is pink. The cells are fusiform in shape and extend
propels blood into them.
around the vessel. High magnification.
Importantly, between each heart beat
the elastin recoils and this returns
the vessels to normal dimensions
and helps propel the blood along
the arteries and thus maintain blood
flow and pressure.
■ Distributing arteries have a high
proportion of smooth muscle cells
in their walls and this is related to
their ability to maintain muscle
tone (a state of prolonged, partial
contraction) and thus arterial blood
pressure, particularly in the
periphery of the body. The internal
elastin lamina in distributing arteries
Smooth muscle cell nuclei
(Fig. 10.6) is pronounced in contrast
to that in conducting arteries.
Distributing arteries include the Lumen of arteriole
arteries of the limbs.
■ Arterioles are much smaller in
diameter than arteries though they Endothelial cell nucleus
share a pattern of layers in their
walls similar to that of distributing
arteries. However, they have only
one to three layers of smooth
muscle in their tunica media. The
smooth muscle cells are arranged
concentrically in the walls of
arterioles (Figs 10.7 and 10.8) and so
their contraction and relaxation
alters the diameter of their lumina.
(This contraction does not pump
blood along the vessels; instead, it Fig. 10.8 Arteriole sectioned (partly) along its length. Some nuclei of the smooth muscle cells in
the wall of this arteriole appear circular. These smooth muscle cells are fusiform in shape and encircle
varies the amount of muscle tone
the arteriole but have been sectioned across their length and through the region of the nucleus.
and thus provides varying resistance Contrast this appearance with the nuclei of smooth muscle cells in Fig. 10.7. Similarly, contrast the
to the flow of blood.) In general, the fusiform shape of the endothelial cell nuclei lining this arteriole with those in Fig. 10.7. High
sympathetic part of the autonomic magnification.
nervous system controls the amount

of tone (contraction) of the smooth
muscle in the walls of arterioles and
Capillary lumen
thus the rate of blood flow to
capillaries.
Capillaries
Most capillaries are 4–10 μm in diameter
and most are also short in length. They
are perfused by blood from arterioles.
Networks of branching and connecting
(anastomosing) capillaries are present in
many regions of the body and are referred Capillary lumen
to as capillary beds. Capillary walls (Figs
10.9 and 10.10) are formed by a single
layer of squamous epithelial cells known
as endothelial cells, and their basement
membrane (Fig. 10.10). The endothelial
cells form the narrow tubes of the capil-
laries through which blood cells and Red blood cells in lumen of
plasma flow. Around the periphery of venule
some capillaries are pericytes, which
have long cytoplasmic processes that
wrap around the walls of capillaries. Peri-
cytes contain contractile proteins and Fig. 10.9 Capillaries and venules. Erythrocytes appear as ghostly circles and can be used to
thus are able to contract and modify the estimate the size of the vessels. Connective tissue (green) surrounds the vessels. Special stain. High
flow of blood through capillaries. After magnification.
injury, pericytes are able to differentiate
and form new blood vessels and support-
ing connective tissue.
Basement membrane
Although capillaries are very small,
they are vital in the functioning of the
cardiovascular system as they are the Endothelial cell cytoplasm
site where exchange of gases, nutrients
and waste molecules takes place. They
Red blood cell in lumen of
are also important sites where some of
capillary
the components of blood plasma and
white blood cells pass between capillar-
Cell junction
ies and surrounding tissues. Capillaries
may be categorised into three groups: Endothelial cell cytoplasm
continuous, fenestrated or sinusoidal.
Heterochromatin of endothelial
These groups have significant morpho- cell nucleus
logical and functional differences and
are present in different locations.
■ Continuous capillaries. These are Euchromatin of endothelial cell

located in brain, spinal cord, nucleus
peripheral nervous tissue, muscle
and connective tissues (Fig. 10.9).
The endothelial cells lining these Fig. 10.10 Electron micrograph of a capillary. One endothelial cell was sectioned through its
capillaries are tightly joined together. nucleus: it displays hetero- and euchromatin. Its cytoplasm is attached to another endothelial cell by a
specialised cell junction. The cytoplasm of the attached endothelial cell, not sectioned through its
Gases diffuse through the
nucleus, extends around the lumen. Low magnification.
endothelial cells and pinocytosis and
exocytosis occur in many regions,
passing fluid and molecules through
the cells. large molecules, e.g. hormones, to (openings) in the cytoplasm of
■ Fenestrated capillaries. The pass readily across the capillary walls. endothelial cells and these do not
endothelial cells in these capillaries ■ Sinusoidal capillaries. Sinusoidal have diaphragms across them.
are tightly joined together but they capillaries differ from other Sinusoids are generally wider in
exhibit tiny pores. These pores are capillaries in that the endothelial diameter than capillaries and their
closed by diaphragms formed of cell cells do not form a continuous layer shape contours around adjacent
membranes. This type of capillary is of tightly attached cells; their parenchymal cells. In the walls of
present in endocrine glands and the basement membrane is also some sinusoids, e.g. in the spleen
gastrointestinal tract and allows some discontinuous. They have fenestrae and liver, fixed macrophages are
present. The structure of the walls of endothelial covering and a fibrous core returning some excess extracellular
sinusoids, in comparison with the of connective tissue. The flaps project fluid and white blood cells to veins.
walls of other capillaries, facilitates towards the heart; thus, if blood flow to The smallest lymphatic vessels are
greater opportunities for exchange the heart stops, the blood cannot pass lymphatic capillaries. These begin as
activities, particularly those involving backwards because the valve flaps are very small blind-ended tubes formed
cells of the immune system. forced together and close the lumen. by endothelial cells. The extracellular
Valves are particularly important where (tissue) fluid which drains into lym-
there is a need to counteract the force phatic capillaries is known as lymph.
Veins of gravity such as in the limbs. Interest- Lymph capillaries resemble blood capil-
Veins are low-pressure blood vessels ingly, the superficial veins in the lower laries but they are characterised by
compared with arteries, and they return limbs in humans have a well-developed the presence of non-return valves. The
blood to the heart. In general, compared component of smooth muscle in their pressure in lymphatic vessels is very
with arteries, there is much less smooth walls which, by maintaining muscle low and the valves help prevent back
muscle and elastin and more collagen in tone, is thought to assist in preventing flow of lymph. Lymph is carried in
the walls of veins, which accords with excess distension of the veins due to lymph vessels to and from lymph
the lower pressure within them. Fur- gravitational forces. The largest veins, nodes (Chapter 8). As lymph passes
thermore, the ratio of luminal diameter close to the heart, do not have valves through lymph nodes immune
to wall thickness is greater in veins than aiding unidirectional flow. Venous responses to foreign molecules occur
in arteries if the comparison is made return from large veins below the heart and immune cells such as lymphocytes
between vessels adjacent to each other is aided by pressure changes that occur may be added to the draining lymph
in the body (Fig. 10.11). in the thorax during inspiration and (Chapter 8). Lymph draining particular
Veins may be grouped into three gravity aids venous return from the organs and regions of the body passes
categories according to their size: small, vessels above the heart. through specific lymph nodes before
medium and large. The smallest veins, draining into wider lymph vessels
venules, drain capillaries. In medium- (lymph ducts). Eventually, the lymph
sized veins valves are present that Lymphatic vessels ducts join veins in the neck region and
prevent the back flow of blood. Valves The lymphatic vessels are an important thus lymph is returned to the cardio-
are flap-like structures which have an component of the circulatory system vascular system.
Fig. 10.11 Artery and vein. The wall of this

artery contains numerous smooth muscle cells
which have been fixed in the contracted state
(Chapter 5) and the nuclei of the endothelial cells
appear as dark dots projecting into the lumen.
Low magnification.
Wall of artery
Wall of vein
Lumen of vein
Red blood cells
White blood cell

Clinical notes
Varicose veins The non-return valves in the superficial veins of the legs may become incompetent,
particularly after excess pressure has been sustained such as in pregnancy, or in persons ‘on their feet a lot’.
When this happens the valves and veins may become dilated and their position becomes apparent as swellings under
the skin. These veins may be removed surgically, after which blood finds alternative drainage routes to deeper veins.
Deep vein thrombosis Deep veins accompany the deeply placed arteries in the limbs. These veins are of relatively
small calibre and normally venous return is aided by valves. Maintaining tone in the smooth muscle in the walls of these
veins helps prevent the veins from distending. In addition, contraction of skeletal muscles in the limb compresses these
veins and helps propel the blood towards the heart (as long as the valves are effective). During lengthy periods of
inactivity, sufficient venous blood may not be propelled away from the lower limb veins. The blood may become
stagnant and clot (i.e. form a thrombus), blocking the deep veins. This causes the limb to swell and become red and
painful. The particular danger is that the clot or part of it may detach and pass, via the heart, to the lung, where it may
lodge in small blood vessels. This is termed a pulmonary embolism and it can be fatal.
Oedema This is the accumulation of tissue fluid in body tissues which would normally have re-entered venules
and lymphatic vessels. It causes swelling of the affected region. It may be part of a local inflammatory reaction or if,
for example, it is present in both lower limbs it may be due
to increased venous pressure as a result of weak contractions of the right chambers of the heart (right heart failure).
Summary
The circulatory system
■ Consists of the heart and the vessels which carry blood or lymph.
The heart
■ The heart has paired atria and paired ventricles separated by valves which prevent back flow of blood.
■ It has a connective tissue skeleton.
■ It is supplied by autonomic nerves which modify the rate at which it beats.
■ The myocardium, the middle (thickest) layer, is formed mostly by cardiac muscle cells. Specialised cells (e.g. Purkinje cells) are involved in
organising muscle contraction.
■ The endocardium, the inner layer, is lined by endothelial cells.
■ The epicardium, the outer layer, supports blood vessels supplying the heart, may accumulate fat and is part of the pericardium.
Blood vessels
■ These vary in structure and function.
■ Arteries (and arterioles) carry blood at relatively high pressure from the heart to capillaries.
■ Veins (and venules) carry blood at low pressure from capillaries to the heart. Some veins and venules have valves which aid return of blood to
the heart.
■ Capillaries have only endothelial cells in their walls and gases, molecules, white blood cells and fluid move across their walls.
■ Larger blood vessels have three layers in their walls:
■ tunica intima, the inner layer comprising endothelium and connective tissue
■ tunica media, the middle layer comprising varying amounts of elastin, smooth muscle and collagen
■ tunica adventitia, the outer layer of connective tissue binding vessels to adjacent structures.
■ Contraction of smooth muscle in vessel walls is controlled (largely) by sympathetic nerves.
Extracellular (tissue) fluid

■ This is formed from plasma.
■ Some returns to venules and some to lymphatic capillaries which eventually drain into veins.
77
Chapter 11
The respiratory system
The function of the respiratory system system, there are other related struc- decrease intrathoracic volume and
is to transport gases between the atmos- tures that help propel the gases along stretched elastin fibres in the lung (see
phere and sites in the lungs where the passages. Each lung is enclosed by a below) recoil.
gaseous exchange between air and blood pleural sac formed by a serosal mem-
occurs. Oxygen diffuses into blood in brane (Fig. 11.1). The visceral layer of
Upper respiratory tract
capillaries in the lungs and carbon the pleura is firmly attached to the
dioxide is released from the blood. The surface of each lung and the parietal The upper respiratory tract comprises
respiratory system consists of a series of layer to the inner surface of the chest passages and tubes of decreasing diam-
air-filled passages connecting the nose wall. The pleural cavity (the space eter which connect the nose and mouth
and mouth to the two lungs in the enclosed by the pleura) contains fluid to the lower respiratory tract in the
thorax (Fig. 11.1). Two categories of pas- secreted by the serosal cells and the lungs. From the exterior inwards,
sages are described, the upper and the lungs are thus able to move during the upper respiratory tract comprises
lower respiratory tracts. The structure of respiration in a relatively friction-free the nasal cavity, nasopharynx, larynx,
the walls of the passages of the upper environment. The pleural cavity has an trachea, bronchi and some bronchioles.
respiratory tract ensures that they do important role in breathing as the pres- These passages are also known collec-
not collapse during breathing. The sure in the cavity is less than atmos- tively as the conducting portion of the
structure of the walls of the lower respi- pheric pressure. As the thoracic respiratory tract as they conduct air to
ratory tract ensures that efficient gaseous boundaries (the ribs, intercostal muscles the sites of gaseous exchange in the
exchange occurs across a barrier which and diaphragm) move during breathing lungs.
is 0.1–1.5 μm thick. It is also essential the pleural membranes and lungs move During inspiration the upper respira-
that the passages in the lower respira- with them. Inspiration increases tory passages are under increasing nega-
tory tract do not collapse during intrathoracic volume (and the negative tive pressure as the intrathoracic volume
respiration. pressure in the pleural cavities) and increases. Air will be drawn into the
Whilst the respiratory passages draws air into the lungs. Expiration lungs only if the walls of these passages
conduct gases through the respiratory occurs as the thoracic boundaries do not collapse. The larger passages
have bone or cartilage in their walls
which make them relatively rigid and
ensure that they remain patent during
Visceral pleura inspiration. The smallest passages within
Parietal pleura the lungs, the bronchioles, do not have
bone or cartilage in their walls. Bronchio-
les are held open during inspiration as
Nasal cavity
elastin connective tissue fibres attached
Oral cavity to the outer surface of their walls are
Pharynx
stretched as a result of the thoracic
Epiglottis
Larynx volume increasing during inspiration.
Oesophagus Most of the upper respiratory tract is
lined by a mucosa which consists of
Trachea
a respiratory epithelium and a lamina
propria which supports numerous
Primary bronchus blood vessels. In some regions submu-
cosal connective tissue and aggregations
Secondary of lymphoid cells are also present. The
bronchus
Lung respiratory epithelium is described as
pseudostratified with ciliated columnar
Pleural cavity
epithelial cells and goblet cells (Fig.
11.2). The goblet cells secrete mucus
Diaphragm onto the surface of the epithelium and
this traps particulate matter which may
Fig. 11.1 The components of the respiratory system including the arrangement of the pleural be harmful. Importantly, the beating
coverings of the lungs. motion of cilia of columnar epithelial
lium lining the nasopharynx, particu-

larly on its posterior wall where they
form the nasopharyngeal tonsils (ade-
Smooth muscle cell layer noids). These aggregations form part of
a ring of lymphoid cells (Waldeyer’s
ring) around the pharynx. Inhaled and
Cilia
ingested antigenic material (e.g. bacteria
and viruses) may be trapped in this
Respiratory epithelium region and immune responses mounted,
thus protecting the respiratory and gastro-
Debris on surface intestinal tracts from infection.
Larynx
Goblet cell cytoplasm Inspired air passes from the naso-
pharynx into the larynx and then into
the trachea. The larynx has walls con-
BALT taining hyaline cartilage which maintain
the patency of the airway, and most of
the lumen of the larynx is lined by res-
Fig. 11.2 Bronchus (part of wall). The mucus in the cytoplasm of goblet cells in the respiratory piratory epithelium. However, there are
epithelium is stained pink. BALT, bronchus-associated lymphoid tissue. Special stain. High magnification.
flaps (the vocal folds) extending from
the walls of the larynx into the lumen
which are covered by a stratified squa-
cells moves the mucus so that it is swal- nasal cavity. Thus, sniffing odours into
mous epithelium. Vocal cords vibrate
lowed or discharged from the nose or the upper part of the nasal cavity is the
and produce sounds and the stratified
the mouth. In addition, moisture on the most efficient way of detecting smells.
squamous epithelium resists the wear
surface of the respiratory epithelium, Lying adjacent to the nasal cavity are
and tear resulting from the vibrations.
provided by mucus, humidifies inspired paranasal sinuses. They are four paired
During swallowing, the entry to the
air. This prevents dehydration of the structures (the maxillary, frontal, sphe-
larynx from the pharynx is closed tem-
cells lining the lower respiratory tract noid and ethmoid sinuses) which open
porarily by a large flap-like structure, the
where gases have to enter an aqueous into the nasal cavity. These sinuses are
epiglottis. This arrangement prevents
phase to allow exchange between air air-filled spaces in skull bones which are
ingested food and liquid entering the
and blood. The respiratory epithelium lined by respiratory epithelium. The
trachea and producing coughing and
also contains stem cells which can function of the sinuses is unclear, though
choking. The stratified squamous epi-
replace damaged goblet and ciliated epi- it may be related to insulating the brain
thelium covering the anterior surface
thelial cells and replace themselves. from the effects of inspiring cold air.
of the epiglottis is continuous with the
Neuroendocrine cells are also present Other suggested functions include
dorsal surface of the tongue and, as it is
which secrete molecules (paracrine giving resonance to the voice, lightening
in contact with food during swallowing
hormones) that regulate the local the weight of the skull and adding to the
is subject to abrasion. In contrast, the
environment. ability of the upper respiratory tract to
posterior surface of the epiglottis is
‘air condition’ (warm and moisten)
exposed only to air and is covered by
Nasal cavities and sinuses inhaled air.
respiratory epithelium. The flexibility
The openings of the nostrils are guarded In the nasal cavities and the sinuses
and recoil movements of the epiglottis
by short hairs projecting from skin the mucosa and associated blood vessels
during swallowing are aided by its core
which extends a short distance into the are firmly attached to underlying bone
of elastic cartilage (see Fig. 9.1).
nasal cavity. The hairs are efficient at or cartilage, and the rigidity conferred
trapping particles in inspired air. The by such attachments means that inspira-
nasal cavity is separated into left and tion does not collapse the air passages Trachea
right sides by a septum, and respiratory in these regions. The trachea is a tube attached to the
epithelium lines most of the cavities. larynx in the neck and it extends about
The mucosa lining the cavities is highly Nasopharynx 10 cm into the thorax. It is 2–3 cm in
vascular and the vessels are vulnerable, The nasopharynx and the oropharynx diameter and is kept patent by 15 to 20
hence the risk of epistaxis (nose bleeds). are contiguous parts of the pharynx (a incomplete ‘C’-shaped rings of hyaline
The proximity of blood in vessels to the large passage shared by the respiratory cartilage in its wall (Fig. 11.3). Each ring
mucosal surface, particularly in the nasal and the digestive systems). The naso- of cartilage is completed on the poste-
passages, ensures air is warmed as it pharynx, which is traversed by air, is rior wall of the trachea by smooth
travels along the tract. Indeed, air enter- lined by respiratory epithelium, but the muscle and connective tissue containing
ing the nose at 4°C reaches tempera- oropharynx, which carries food (and elastin fibres. The trachea is lined by
tures not much below blood temperature drink and air) from the mouth, is lined respiratory epithelium (Fig. 11.3) and
before arrival at the lower respiratory by a stratified squamous epithelium there are serous and mucous glands
tract. which is able to resist the ‘wear and tear’ (Fig. 11.4) in submucosal connective
Specialised epithelial cells involved in caused by the passage of food. tissue. Secretions from the sub-
detecting smells, olfactory epithelial Aggregations of lymphocytes are a mucosal glands and goblet cells in the
cells, lie in the uppermost parts of the prominent feature deep to the epithe- epithelium are propelled by ciliary
The respiratory system 79
of lung has its own branch of a pulmo-

nary artery as well as a single tertiary
Smooth muscle and connective bronchus, and each has clinical signifi-
tissue
cance. For example, knowledge of the
architecture of bronchopulmonary seg-
ments is vital in bronchoscopy. In addi-
tion, a disease may be confined to one
Connective tissue segment of lung and surgical resection
may be used to remove the diseased
segment. Further branching of bronchi
in segments reduces their diameter to
5 mm and, at this dimension, branching
continues but the passages are then
known as bronchioles.
All bronchi contain hyaline cartilage
in their walls which maintains their
Lumen patency. Primary bronchi have, like the
trachea, incomplete rings of cartilage in
their walls. Intrapulmonary branches of
bronchi have irregularly placed plates of
cartilage in their walls (Fig. 11.5). Large
bronchi are lined by respiratory epithe-
lium (Fig. 11.5), but as they become
Respiratory epithelium
smaller in diameter gradual changes
occur in the epithelium (see below). The
submucosal layer of bronchi contains
serous and mucous glands which secrete
onto the epithelial surface (Fig. 11.6).
Secretions on the epithelial surface are
Hyaline cartilage
moved up the ‘mucus escalator’ to the
pharynx by ciliary activity of the colum-
nar epithelial cells. Smooth muscle
(Figs 11.2 and 11.6) is also present in the
walls of bronchi and the muscle cells are
Fig. 11.3 Trachea (part of wall). Medium magnification. arranged spirally along the length of
the walls. Parasympathetic stimulation
of this smooth muscle causes contrac-
tion which reduces the diameter of the
lumen. Conversely, sympathetic nerve
stimulation relaxes the muscle and
increases the diameter of the airway.
Mucous cell cytoplasm
The strength of muscle contraction is
not great enough to collapse the bronchi
Serous cell cytoplasm
because of the relatively rigid cartilage
lying outside the muscle layer. Aggrega-
tions of lymphocytes are a common
feature in the walls of bronchi (Figs 11.2
and 11.5) and are described as ‘bron-
chus-associated lymphoid tissue’ (BALT).
In these regions, interactions between
Lumen of mucous gland acinus macrophages and lymphocytes take
place which are important in immune
defence of the lungs.
Lumen of serous gland acinus
Bronchioles
Fig. 11.4 Serous and mucous glands. Special stain. High magnification. Bronchioles, passages of less than 5 mm
in diameter, do not have cartilage in
activity toward the pharynx and are enter the lungs and divide into lobar their walls but have smooth muscle (Fig.
usually swallowed. (secondary) bronchi. Each of these sub- 11.7). The patency of bronchioles during
divides about 10 times into segmental inspiration is assisted not by cartilage in
Bronchi (tertiary) bronchi which supply specific their walls but by elastin fibres in sur-
The trachea bifurcates into two main areas of lung known as bronchopulmo- rounding connective tissue attached to
(primary) bronchi (Fig. 11.1). These nary segments. Each of these segments the bronchioles which are stretched as
the thoracic volume is increased during

inspiration and air is drawn into the
respiratory tract.
Interalveolar septum Smooth muscle cells spiral around
bronchioles deep to the epithelium and
Alveolar air space their contraction affects the diameter of
these airways. The state of contraction
of this smooth muscle is the major
factor affecting the volume of air reach-
ing the lower, respiratory portion of the
tract. Parasympathetic nerve impulses
cause these muscle cells to contract and
this reduces the diameter of the bron-
Hyaline cartilage chioles and thus restricts air flow. Con-
versely, sympathetic nerve impulses
relax the muscle cells and this aids air
flow. Indeed, malfunction of this smooth
muscle in asthma so that airways con-
strict, significantly reduces the volume
BALT
of air entering the lungs and results in
the distressing and serious effects of the
disease.
Respiratory epithelium As the conducting tubes of the respi-
Fig. 11.5 Bronchus (part of wall) and alveoli. Medium magnification. ratory system reduce in calibre, the type
of lining epithelium gradually changes.
Instead of the typical respiratory epithe-
lium (pseudostratified, ciliated colum-
nar, with goblet cells) as in the larger
bronchi (Figs 11.2, 11.5 and 11.6), they
Lumen of bronchus become lined by a simple epithelium.
Most bronchioles are lined by a simple
epithelium consisting of ciliated colum-
Goblet cell cytoplasm nar cells and a few goblet cells. Smaller
divisions of bronchioles are lined by cili-
ated low columnar or cuboidal cells (Fig.
11.7); goblet cells are not present in the
Smooth muscle smaller bronchioles. In terminal bron-
chioles the epithelium may become flat-
tened taking on a squamous appearance
Red blood cells in vessel
(Fig. 11.8). There are also specialised
cells (Clara cells) in the epithelium
lining the smallest bronchioles which
may serve a protective function. (Clara
Lumen of mucous gland cells are prominent in some non-human
species.)
There are no submucous glands in
bronchioles and very few goblet cells. If
Alveolar air space such glands and goblet cells were present,
it could lead to too much fluid in the
bronchioles which may drain into and
‘drown’ the gaseous exchange region of
the lower respiratory tract.
Lower respiratory tract

The most distal, lower part of the respi-
ratory tract is also described as the
respiratory portion of the tract as it is
here that gaseous exchange between air
and blood occurs. The walls of the pas-
Fig. 11.6 Bronchus (part of wall) and lung alveoli. Arrows show the width of an interalveolar sages are at their thinnest and this facili-
septum. Erythrocytes appear as bright red dots; some are visible in the septa. Connective tissue is blue/ tates the exchange of gases. Terminal
green. Special stain. Low magnification. bronchioles continue as respiratory
The respiratory system 81
bronchioles. In some parts of respira-

tory bronchioles the epithelium is
simple cuboidal, but in other parts squa-
mous epithelial cells are present and
gaseous exchange occurs across the cells Smooth muscle
in these regions.
Respiratory bronchioles open into Lumen of bronchiole
alveolar ducts, which in turn lead to
several alveoli (Fig. 11.8). Some alveoli
are adjacent to each other and share their
walls. These walls are known as interal-
veolar septa (Figs 11.5–11.8). There are
Cuboidal epithelium
several hundred million alveoli per lung
offering an enormous surface area where
gaseous exchange occurs.
The epithelium lining alveoli lies very
close to a capillary network and it is
across this air–blood barrier that gases,
in the aqueous phase, diffuse. The
barrier between air and blood is very Alveolar air space
thin (Figs 11.6 and 11.7) and consists of
(Fig. 11.9):
■ an alveolar epithelium and its

basement membrane
■ connective tissue (sparse)
■ a capillary endothelium and its
basement membrane.
Fig. 11.7 Bronchiole (part of wall) and lung alveoli. Arrows show the width of two interalveolar
septa. Connective tissue is red. Special stain. High magnification.
The alveolar epithelium comprises
type I and type II pneumocytes. Type I
pneumocytes make up the majority of
Terminal bronchiole
the surface of alveoli and their cyto- Cuboidal epithelium (lumen)
plasm forms a very thin layer closely
applied to the basement membrane: this Clara cells
Respiratory bronchiole
aids the diffusion of gases. Type II (lumen)
pneumocytes are roughly spherical cells
which synthesise and secrete a sur-
factant (a lipid material with detergent- Squamous epithelium
like qualities) which reduces surface Alveolar duct (lumen)
tension in the alveoli. During inspiration
this low surface tension makes it easier Connective tissue fibres
to draw air into the alveoli and helps to (e.g. elastin) Capillary
prevent the alveoli from collapsing. Alveolus (lumen)
The connective tissue around alveoli Interalveolar septum
is sparse (Figs 11.6 and 11.7) and con-
Type I pneumocyte
sists mainly of elastin fibres, although a
little collagen is present. The elastin Type II pneumocyte
fibres are stretched on inspiration and
this helps to draw air into the alveoli. Capillary network
Importantly, recoil of the elastin during
expiration helps to expel air from the Fig. 11.8 The microscopic structure of the terminal components of the airway.
alveoli. In some regions there is no con-
nective tissue and the basement mem- cells which phagocytose particulate phages may migrate onto the surface of
branes of an alveolar epithelium and matter, including bacteria, and others the epithelium and others may remain
the adjacent capillary endothelium are which mount immune responses to in the lungs throughout life. Macro-
fused, thus reducing the distance gases foreign molecules. Lying on the alveoli, phages are particularly apparent if
have to travel between air and blood on the air side or apparently lying free they have ingested inert particles such
(Fig. 11.9). within the air space, are alveolar macro- as carbon and this can give lungs a
Throughout the lungs a variety of phages. These cells are also present black appearance at post-mortem
immune cells are present. These include within interalveolar septa. Some macro- examination.
Fig. 11.9 The microscopic structure of the

Red blood cell
Fused basement blood–air barrier.
membranes Type I pneumocyte
Air Air
Capillary Type II pneumocyte

endothelial cell
Alveolar epithelium Connective tissue (elastin)

separating basement
membrane of endothelium
and pneumocytes
Clinical notes
Infantile respiratory distress syndrome Prior to 28 weeks of development in utero, type II
pneumocytes are unable to synthesise surfactant and, as a consequence, alveoli do not fill with air on
inspiration; as a result, premature infants may not survive. In addition, the alveolar wall before about 26 weeks of
development is insufficiently thin to enable gaseous exchange.
Smoking Goblet cells increase in number and ciliated cells decrease in number in smokers. One consequence is
mucus is not cleared readily from the respiratory passages. Coughing may help clear the passages and prevent mucus
from reaching the alveoli and decreasing the efficiency of gaseous exchange. Smoking is associated with an increased
risk of heart disease and lung cancer.
Asthma In this condition the airways are abnormally constricted by contraction of the smooth muscle, particularly
in the bronchioles. It is often a consequence of immune (allergic) reactions. In asthmatics the airways are inflamed
and produce excessive amounts of mucus. Attacks are usually acute episodes of wheezing, coughing and difficulty in
breathing. These episodes may be effectively treated with inhalers containing drugs which dilate the airways, and
steroid-based drugs which reduce the inflammation.
Cystic fibrosis This is an inherited condition in which excessive amounts of viscous mucus are produced. It is
often thought of as a purely respiratory disorder but it is a disorder of exocrine glands. The excess secretions of the
exocrine glands cause obstruction in the lungs and a range of other organs such as the pancreas, liver and intestines.
The disease pursues a chronic course and sufferers rarely live beyond their third decade.
Summary
■ The respiratory system consists of the lungs and a series of passages carrying air to them:
■ the upper respiratory tract passages transport air to and from the lower respiratory tract, where exchange of gases (oxygen and carbon
dioxide) between blood and air occurs.
■ The chest wall, diaphragm and pleural membranes around the lungs are involved in moving air in and out of the lungs (during inspiration
and expiration).
■ The walls of the trachea and bronchi contain hyaline cartilage which provides rigidity and prevents the passages collapsing during inspiration:
■ all these passage are lined by the typical respiratory epithelium.
■ The walls of bronchioles do not contain cartilage and they are kept open during inspiration as elastin fibres attached to their walls are
stretched:
■ the respiratory epithelium is gradually replaced in bronchioles by a simple columnar or cuboidal (non-ciliated) epithelium.
■ Smooth muscle is present in the walls of bronchi and bronchioles and is controlled by autonomic nerves.
■ The walls of the lower respiratory tract are extremely thin and gaseous exchange occurs mostly in alveoli.
■ The blood–air barrier in alveoli comprises:
■ endothelial cells and their basement membrane, sparse elastin fibres, alveolar epithelial cells and their basement membrane
■ alveolar epithelium is formed mostly by very flattened cells (type I pneumocytes), and some type II pneumocytes which are rounded and
secrete surfactant.
■ Aggregations of immune cells are present in the walls of the respiratory tract and macrophages are present in alveolar walls and on the
surface of the alveolar epithelium.
83
Chapter 12
The digestive system
The digestive system consists of the ali- canal is lined by a stratified, squamous components of food that have not been
mentary canal, which is a tube connect- epithelium which is not keratinised. digested. The stored, undigested food
ing the mouth and anus, and associated The digestive system has two primary and waste products of the body, e.g.
structures that facilitate digestion of functions. It breaks down food and from the breakdown of red blood cells,
ingested food and drink (Fig. 12.1). The drink into small molecules such as are emptied from the alimentary canal
alimentary canal comprises the mouth, glucose, amino acids, fatty acids and at defecation.
oesophagus and gastrointestinal tract. triglycerides, a process which involves The structure of the alimentary canal
The gastrointestinal tract comprises the enzymic activity and is known as diges- is related to its functions and different
stomach, duodenum, jejunum, ileum, tion. The second primary function of aspects of function occur at different
colon, appendix, rectum and the upper the digestive system ensures the small locations along the canal. The gastro-
part of the anal canal. The associated molecules produced by digestion in the intestinal tract itself is several metres in
structures are the teeth, tongue, salivary lumen of the alimentary canal enter the length in humans, which is a reflection
glands, liver and pancreas. At the mouth, body ‘proper’ by being absorbed across of the space required to accomplish all
lips intervene between skin and the the epithelium lining the alimentary aspects of its function and is related to
mouth and they are covered by a strati- canal and into the blood or lymphatic the transit times required for these
fied squamous epithelium which is not vessels. In addition, the digestive system functions.
keratinised. At the anus the stratified, absorbs water, minerals, vitamins and
keratinised squamous epithelium of ions from the material in the lumen of
General structure of the
skin extends a short distance into the the gastrointestinal tract. The terminal
alimentary canal
anal canal. The upper part of the anal part of the tract functions as a store for
All the alimentary canal is lined by a
mucosa (Chapter 3), which consists of
an epithelium, connective tissue lamina
propria and, in many regions, a layer of
smooth muscle forming the muscularis
mucosae (Fig. 12.2). The epithelium
of the mucosa reflects the primary
Pharynx function(s) occurring in that region.
However, in all regions the mucosa is
important in forming a barrier between
substances ingested, including micro-
Oesophagus organisms, and the internal environ-
ment of the body. In regions where the
muscularis mucosae is present, contrac-
Cardiac region tion of this muscle moves and folds the
of stomach Diaphragm
mucosa, aiding contact between the con-
Fundus of stomach tents of the lumen and the surface epi-
Liver thelial cells.
A submucosal layer of connective
Pylorus of stomach Body of stomach tissue, which supports nerves and blood
Duodenum Jejunum and lymph vessels, attaches the mucosa
Transverse colon in most parts of the alimentary canal to
Pancreas
outer layers of muscle (the muscularis
Ascending colon
Descending colon externa) (Fig. 12.2). In most regions of
Ileum
the alimentary canal two layers of
Sigmoid colon
Caecum muscle are present in the muscularis
Rectum externa. In the outer, longitudinal layer
Appendix Anal canal the long axis of each muscle cell lies
Anus roughly parallel to the length of the
lumen. In the inner, circular layer the
Fig. 12.1 Components of the digestive system. long axes of the muscle cells lie around
Serosa each other, potentially damaging friction

(parietal peritoneum) Blood vessel
does not occur. In addition, the peritoneal
Mesentery (double layer membranes enclose the vessels and
of peritoneal membrane nerves supplying the gut tube.
Peritoneal cavity enclosing blood vessel to
gastrointestinal tract) Specialised gut-associated lymphoid
tissue (GALT) is present in the walls of
Submucosal gland
Accessory gland, e.g. liver the alimentary canal. In some regions,
Submucosal GALT forms large structures, e.g. tonsils;
connective tissue Serosa
(visceral peritoneum) in other regions, only small clusters of
Outer longitudinal lymphoid cells are present (Fig. 12.2).
smooth muscle Gut-associated lymphoid
tissue (GALT) These cells are part of the primary
Inner circular
smooth muscle defence mechanisms against pathogens
entering the body across the mucosa
Muscularis mucosae Epithelium Mucosa lining the gut tube.
Lamina propria
Mouth
The mouth (oral cavity) contains the
Fig. 12. 2 Generalised transverse section through the gastrointestinal tract. The outer and inner
smooth muscle layers form the muscularis externa. tongue and teeth. The epithelium of the
mucosa lining the cheeks and tongue
is able to resist the wear and tear in-
volved in chewing food, and in most
regions it is a stratified, squamous (non-
keratinised) epithelium. This epithelial
Lumen of serous gland acinus
surface is moistened by secretions from
small serous and mucous glands in the
submucosal layer and from salivary
glands (Fig. 12.3) which drain their
saliva into the oral cavity. Physical break-
down of food occurs in the mouth and
it is mixed with salivary gland secretions
which begin to break down large carbo-
Adipocyte hydrate molecules.
Salivary glands
There are three, paired salivary glands,
the parotid, submandibular and sub-
lingual glands. Each gland is invested by
Serous demilune a connective tissue capsule, and connec-
tive tissue forms trabeculae which pen-
Cytoplasm of mucous cell etrate the glands and provide support
for the blood vessels and nerves supply-
ing the glands and for the ducts drain-
Lumen of mucous gland acinus ing them. Each gland has secretory cells
arranged as compound, tubuloacinar,
exocrine glands (Chapter 3). The secre-
Fig. 12.3 Submandibular gland, serous and mucous glands. The carbohydrate content in the tory acini drain into small ducts (lined
cytoplasm of mucous gland cells is palely stained and the protein content of serous cells is darkly by a simple cuboidal epithelium) which
stained. Empty spaces are where lipid in adipocytes has been extracted. Medium magnification. join together in a branching system; the
larger ducts are lined by columnar epi-
thelial cells, which may be stratified.
the lumen. Contractions of the muscu- nal cavity, the muscularis externa is The ducts drain the saliva into the oral
laris externa cause peristalsis, which covered by a serosal membrane (Chapter cavity.
provides the motive force transporting 3) which is the inner (visceral) layer of Two types of secretory cell, serous
the luminal contents of the canal the peritoneum. The visceral peritoneal and mucous cells, are present in salivary
towards the anus. In the submucosal membrane is continuous with the pari- gland acini (Fig. 12.3) and, respectively,
layer and the muscularis externa, para- etal peritoneal membrane, which is they produce a watery secretion contain-
sympathetic neuronal cell bodies are attached to the abdominal walls (and part ing proteins which function as enzymes
present and some are involved in co- of the liver). Squamous epithelial cells on and a viscous mucus in which large
ordinating muscle activity. the surface of the peritoneal membranes carbohydrate complexes are major com-
In some regions of the alimentary canal secrete small amounts of fluid into the ponents. In addition, myoepithelial cells
the muscularis externa is attached to adja- peritoneal cavity. The surface of perito- wrap around the acini and their contrac-
cent structures by connective tissue neal membranes is kept moist by these tions help to expel the secretions. The
known as the adventitia. However, in secretions, which provide lubrication to secretions assist the process of digestion
most regions of the canal in the abdomi- ensure that, as gut tubes move against by moistening and lubricating the food,
The digestive system 85
and by providing enzymes. The main

enzyme is amylase, which breaks down
large carbohydrate molecules. Saliva is
also responsible for lubricating and Lumen of duct
cleansing the oral cavity. It contains bac-
tericidal substances such as lysozyme
secreted by serous cells and may contain
immunoglobulin A secreted by plasma
cells.
Parotid glands
The parotid glands are the largest of the Cytoplasm of serous cells
salivary glands. Each parotid gland is
located close to an ear, and each duct
drains into the oral cavity near the
ipsilateral second upper molar tooth.
Serous cells line the acini and form the
majority of the parenchyma of the parotid
glands (Fig. 12.4). Adipose cells appear in Adipocytes
the parotid glands with age. Many small
ducts are distributed throughout the
parenchyma of parotid glands and they Fig. 12.4 Parotid gland. Medium magnification.
are lined by epithelial cells which stain
readily with eosin (Fig. 12.4).
Submandibular glands
A submandibular gland lies beneath the phocytes deep to the epithelium. In Pharynx and oesophagus
mandible on each side, wrapped around addition, three distinct types of pro- Swallowed food and drink pass via the
the muscle which supports the tongue. jection known as papillae are also pharynx to the oesophagus (gullet). The
Each gland drains via a duct that opens described, and all assist in macerating structure and function of the epithelium
on the ipsilateral side of the ridge (the food and resisting abrasion: lining the component parts of the
frenulum) on the undersurface of the pharynx are described in Chapter 11.
■ Filiform papillae. These are
tongue. Mucous glands are a prominent Aggregations of lymphoid cells are a
numerous on the upper surface and
feature of submandibular glands, but prominent feature of the walls of the
are in parallel rows which converge
serous cells are also present. The arrange- pharynx and form tonsils (Fig. 12.5).
towards the midline. The surface
ment of the serous and mucous gland The lymphoid cells are important com-
of these papillae is covered by a
cells together in some acini is such that ponents of the immune mechanisms
keratinised, stratified squamous
these are described as mucous glands defending the alimentary canal (and the
epithelium.
with serous demilunes (Fig. 12.3). respiratory tract).
■ Fungiform papillae. These are covered
The major part of the oesophagus is
by a stratified (non-keratinised)
Sublingual glands in the thorax, but a small segment lies in
squamous epithelium. Specialised
The sublingual glands are the smallest the abdominal cavity and is continuous
clusters of sensory cells (taste buds)
of the salivary glands. Mucous gland with the stomach. The structures in the
are present in the epithelium
cells are predominant in sublingual walls of the oesophagus conform to the
covering this type of papilla.
glands and the ducts open directly into general plan for the gastrointestinal tract
■ Circumvallate papillae. There are
the floor of the oral cavity, rather than (Fig. 12.2). In the thorax, the connective
8 to 12 large, circumvallate papillae
via a single duct system. tissue of the adventitia binds the muscu-
visible to the unaided eye just
laris externa of the oesophagus to adja-
anterior to the ‘V’-shaped groove of
Tongue cent structures. The muscularis externa
the tongue. They are also covered
The tongue is covered by a stratified, consists of an outer, approximately lon-
by a stratified (non-keratinised)
non-keratinised, squamous epithelium gitudinal layer and an inner circular
squamous epithelium which
which on the undersurface is similar to layer. In the upper part of the muscularis
contains taste buds.
the epithelium lining the mouth. The externa, striated voluntary muscle (Fig.
upper surface of the tongue is divided Deep to the mucosa of the tongue 12.6) is present, whereas in the lower
by a ‘V’-shaped groove into an anterior there are numerous, small serous and region it is replaced by smooth involun-
(two-thirds) and a posterior region mucous glands which secrete onto the tary muscle. In the middle region there
developed from different parts of the surface of the epithelium. The major is a transition between the two types of
embryo (see Mitchell B, Sharma R. component of the inner part of the muscle. Coordinated contraction of
Embryology: An Illustrated Colour Text. tongue is skeletal muscle (see Fig. 5.7). muscle cells in the different regions of
Elsevier: 2004). The stratified squamous The bundles of muscle cells are arranged the oesophagus ensures that swallowed
epithelium on the upper surface is in a complex three-dimensional mesh- food and drink normally pass to the
studded by prominent projections. In work and coordinated contraction of the stomach. In some regions, the submu-
the posterior region, many of the projec- muscle cells is important in chewing, cosal tissue of the oesophagus contains
tions are due to aggregations of lym- swallowing and in sound production. serous and mucous glands in addition to
blood vessels, nerves and aggregations of

lymphoid cells. The epithelium of the
mucosa lining the oesophagus is strati-
fied and squamous (Fig. 12.6) and is able
Stratified squamous epithelium to resist friction from swallowed food
and chemical attack by swallowed drinks,
e.g. alcohol.
Lymphocytes and immune related The gastrointestinal tract

cells
Stomach
The stomach is a dilated portion of the
Lymphocytes (densely packed)
gastrointestinal tract. It is described as
having four regions: the cardiac region,
the fundus, the body and the pylorus
(Fig. 12.1). The cardiac region is continu-
Fig. 12.5 Tonsil. This displays a secondary lymphoid follicle as there are palely stained cells in the
ous with the lower end of the oesopha-
centre of a follicle indicating an immune response was occurring. Lymphocytes at the edge of the
follicle are densely packed. The epithelium covering the tonsil is typical of the oropharynx. Low gus. The fundus is the part of the
magnification. stomach lying closest to the diaphragm
and is a site, in humans, where gas
collects. The body of the stomach is
the largest part of the stomach and
the pylorus connects the body of the
stomach to the duodenum. The stomach
produces 2–3 litres/day of gastric secre-
tions (juices) and the main constituents
are mucus, water, hydrochloric acid and
enzymes able to digest carbohydrates,
fats and proteins. The mixture of gastric
juices and ingested food and drink is
Striated voluntary muscle cells known as chyme. The structure of the
stomach conforms to the general plan
(Fig. 12.2) with some modifications
which relate to its functions.
The stomach is covered by a serosal
(peritoneal) membrane. The surface
squamous epithelial cells of the perito-
neal membrane secrete small amounts
of fluid (into the peritoneal cavity) and,
as the stomach fills with food and drink,
it moves relatively easily against adja-
Submucosal connective tissue cent structures. Within the connective
tissue of the peritoneal membrane large
accumulations of fat cells may be
present. The muscularis externa of the
stomach differs from the general plan in
that it has three layers: an innermost
oblique, a middle circular and an outer
longitudinal layer. These muscle layers
help prevent overdistension of the
stomach and their contractions help mix
the chyme and move it towards the
Connective tissue lamina propria small intestine. In the pyloric region
of the stomach, at the gastroduodenal
junction, the muscularis externa is
thickened and functions as a sphincter.
Stratified squamous epithelium The sphincter is controlled by auto-
nomic nerves and hormones which
regulate the passage of chyme into the
duodenum. In contrast, at the gastro-
oesophageal junction, stomach contents
Fig. 12.6 Oesophagus, upper region. Striated voluntary muscle cells can be identified by the normally are not regurgitated into the
peripheral position of their nuclei. The distinction between the connective tissue forming the layers of oesophagus although a distinct muscu-
lamina propria and submucosa is not possible at this magnification. Low magnification. lar sphincter is not apparent.
The interior of the empty stomach is channels known as gastric pits (Fig. fundus) the gastric glands are straight
characterised by thick folds which run 12.7). All the epithelial cells on the tubules and the epithelium lining them
longitudinally. They are known as rugae surface of all regions of the stomach and contains several types of cell:
and are formed by submucosal and lining all the gastric pits are columnar
mucosal layers. The rugae unfold as the and they secrete mucus (Fig. 12.8). This ■ Zymogenic (chief) cells (Fig. 12.9).
stomach fills. They also help to channel mucus forms a thick protective layer These produce and secrete
chyme towards the pylorus and help to which helps to ensure that the stomach pepsinogen (and lipase, which
maintain a large interface between the cells are not damaged by gastric secre- digests lipids). Pepsinogen is inactive
contents of the stomach and the surface tions. At the base of the pits, gastric until it is converted by the acidity of
epithelium. glands extend as tubes deep into the the gastic juices, into pepsin, which
The gastric mucosa has a simple epi- lamina propria and reach the muscularis breaks proteins down into smaller
thelium which contains a variety of cell mucosae. The gastric glands secrete molecules. The release of gastric
types and it is supported by a sparse various substances which drain into the enzymes is stimulated by the vagus
lamina propria. The underlying muscu- pits, and from there to the lumen of nerve, which is part of the
laris mucosae is atypical in that it has the stomach. In the cardiac and pyloric parasympathetic nervous system.
three layers of smooth muscle. It actively regions of the stomach gastric glands are ■ Oxyntic (parietal) cells (Fig. 12.9).
moves the mucosa, thus increasing coiled tubules lined by columnar cells These produce and secrete
contact between mucosa, gastric juices which secrete mucus. Their appearance hydrochloric acid, which helps
and ingested substances. in routine H&E-stained sections resem- provide the optimum pH for
The epithelium of the gastric mucosa bles the mucous cells lining gastric pits. enzymes secreted by zymogenic
dips into the lamina propria and forms In the rest of the stomach (body and cells. The acid also destroys some
Lumen Gastric pit
Columnar mucous cell cytoplasm

Mucous cells
Neuroendocrine cells
Oxyntic cells
Zymogenic cells
Neck region
Lumen Columnar mucous cell cytoplasm
Gastric
gland
Columnar mucous cells
(sectioned transversely)
Lumen of stomach
Lamina propria
Fig. 12.7 Epithelial cells lining a gastric pit
and gastric glands (typical of the fundus and
body region). Fig. 12.8 Stomach, body region showing gastric pits. Arrows show the entrance to pits. Medium
magnification.
Fig. 12.9 Stomach, body region showing

gastric glands. The eosinophilic cytoplasm of
oxyntic cells distinguishes them from the
basophilic cytoplasm of the zymogenic cells.
Large numbers of mitochondria in the cytoplasm
of oxyntic cells and large amounts of cytoplasmic
RNA in zymogenic cells account for the difference
Oxyntic (parietal) cell nuclei in staining. Medium magnification.
Zymogenic (chief) cell nuclei

ingested microorganisms. Secretion continues in the small intestine and

of acid is stimulated by the vagus involves digestive enzymes from secretory Clinical note
nerve too. Oxyntic cells also secrete cells in the mucosal epithelium and, in the Stomach ulcer Some
intrinsic factor, which is necessary duodenum, in the submucosa. Secretions stomach ulcers are the
for the absorption of vitamin B12, also enter the lumen of the duodenum result of damage to epithelial cells
which is essential, in turn, for the from the pancreas and liver and these also lining the stomach by specific
production of red blood cells. aid digestion. The luminal contents, molecules, e.g. alcohol or aspirin.
Without intrinsic factor pernicious known as chyle, have a transit time along If epithelial cells are killed by
anaemia develops. the small intestine of 3–4 hours and diges- such molecules the damage may
■ Mucous neck cells. These are tion is largely completed in that time. be repaired by the normal
columnar cells near to the junction Most of the products of digestion, e.g. proliferative activity of stem cells
of gastric pits and glands and they amino acids and monosaccharides, are in the epithelium. However, if the
secrete mucus. absorbed across the epithelium lining the damage is extensive and the
■ Stem cells. These are located amongst small intestine and pass into blood vessels; production of replacement cells
the mucous neck cells and, although fatty acids and triglycerides pass into lacte- inadequate, the damage may
relatively few in number, are able to als (small, blind-ended lymph vessels). extend into the connective tissue
undergo mitosis and give rise to The wall of the small intestine con- lamina propria and bleeding into
replacement gastric epithelial cells of all forms to the generalized structural plan of the gastric lumen may occur.
types. Some offspring cells differentiate the gastrointestinal tract (Fig. 12.2) though
and migrate into their appropriate there are features which characterise each
location within the epithelium; others part. The epithelium of the mucosa lining
remain as stem cells. the small intestine contains: There are several structural features
■ Neuroendocrine cells. These secrete a of the small intestine that facilitate
■ columnar epithelial cells (Fig. 12.10), contact between luminal contents and
variety of hormones into the local
which are specialised for absorption the mucosal epithelium and thus aid
environment and into blood vessels
of small molecules from the lumen digestion and absorption of the mole-
that modify the activity of other
(see below) cules produced by enzymic activities:
cells. For example, in the mucosa
■ goblet cells, which make and secrete
of the stomach some cells secrete
mucus that helps to protect the ■ Transverse folds. These are visible in
gastrin, which stimulates contraction
luminal surface (Fig. 12.10) the duodenum, jejunum and first
of the muscularis externa of the
■ Paneth cells, which make, store and half of the ileum to the unaided eye.
stomach and relaxation of the
secrete lysozyme (Fig. 12.11) These folds are formed by the
pyloric sphincter, thus moving
■ neuroendocrine cells, which secrete mucosa and submucosa and are
stomach contents into the
molecules that affect the function of known as plicae circulares.
duodenum.
other cells ■ Villi (Figs 12.12 and 12.13). These
Small intestine ■ stem cells (Fig. 12.11) (see below) are present throughout the small
The small intestine has three parts: duo- ■ lymphocytes, which may be between intestine and are microscopic finger-
denum, jejunum and ileum. Digestion the epithelial cells (Fig. 12.10). like structures which project from
Fig. 12.10 Small intestine, part of villus

Small lymphocyte sectioned along its length. The brush border
represents the microvilli increasing the surface
area of the absorptive, columnar epithelial cells.
The mucus in the goblet cells is stained blue.
Connective tissue lamina propria Special stain. High magnification.
Goblet cell cytoplasm
Columnar epithelial cell cytoplasm
Brush border
Smooth muscle cells

Fig. 12.11 Small intestine, base of intestinal

gland. Cells undergoing mitosis have
characteristically condensed chromatin. In the
base of intestinal glands stem cells divide and
one in the anaphase stage of mitosis (Chapter 2)
is displayed. Paneth cells are distinguished by
their position at the base of the intestinal glands
and their eosinophilic granules. High Lumen of intestinal gland
magnification.
Granules in Paneth cells
Stem cell in mitosis
Fig. 12.12 Small intestine, intestinal glands Lumen of small intestine

and part of a villus sectioned along its
length. Special stain. Low magnification.
Epithelium of villus
Connective tissue lamina propria
Smooth muscle
Lumina of intestinal glands
Lumen of intestinal gland
Muscularis mucosae
the mucosa into the lumen (Figs Fig. 3.4) and which appear as finger- activity (Fig. 12.11) of stem cells in the
12.12 and 12.13). They are covered like projections when examined by epithelium at the base of intestinal
by columnar epithelial absorptive an electron microscope. glands which ensures that new cells are
cells and goblet cells (Fig. 12.13) and ■ Intestinal glands (crypts of produced. Some of the new cells differ-
have a core of connective tissue Lieberkühn). These are tubes which entiate and become columnar epithelial
supporting blood vessels and dip into the mucosa as far as the cells, others become goblet cells, yet
lymphatic vessels (lacteals). A few muscularis mucosae (Fig. 12.12). As others remain as stem cells. The new
smooth muscle cells are also present well as columnar epithelial and columnar and goblet cells migrate from
in villi (Figs 12.10, 12.12 and 12.13) goblet cells, Paneth cells (Fig. 12.11), the intestinal glands along the epithe-
and their contractions move the villi neuroendocrine cells and stem cells lium and up to the tip of the villus
amongst the chyle, thus aiding (Fig. 12.11) are present in the where, in turn, they die.
absorption. epithelium of intestinal glands. The first part of the small intestine,
■ Microvilli. These are small folds in the duodenum, is characterised by the
the apical membrane of each The life span of epithelial cells in the presence of glands in the submucosal
columnar epithelial cell which are mucosa of the small intestine is less layer (Fig. 12.14). These glands (Brun-
revealed by the light microscope as a than a week; cells at the tip of villi die ner’s glands) make and secrete alkaline
‘brush border’ (Fig. 12.10; see also and are rapidly replaced. It is the mitotic mucus which helps neutralise the acidic
Fig. 12.13 Small intestine, villi sectioned

transversely and longitudinally. Villi
characterise small intestine, and when they are
sectioned transversely they appear as islands of
Connective tissue lamina propria cells surrounded by the space of the lumen.
(When intestinal glands are sectioned (in large
and small intestine) they do not appear as islands
of cells.) High magnification.
Lumen of small intestine
Smooth muscle
Columnar epithelial cells
Fig. 12.14 Small intestine, duodenum,

submucosal (Brunner’s) glands, gut
(mucosa)-associated lymphoid tissue (GALT)
and the base of intestinal glands. Goblet cell
cytoplasm is stained blue/turquoise. Special stain.
Low magnification.
Lumina of submucosal glands
Lymphocytes (GALT)
Lumen of intestinal gland

chyme entering from the stomach.

Secretions from neuroendocrine cells Lumen of large intestine
in the duodenum inhibit the action of
gastrin and help control the flow of Columnar epithelial cell nucleus
gastric contents to the duodenum.
Within the walls of the small intestine
there is a variety of immunocompet-
ent cells, including lymphocytes (mainly
T cells), plasma cells (mainly secreting
IgA), eosinophils, mast cells and macro- Connective tissue lamina propria
phages. Clusters of immune cells
(GALT) are present and usually are in
the submucosal layer (Fig. 12.14) or the Goblet cell cytoplasm
lamina propria. The ileum, however, is
characterised by the presence of large Columnar epithelial cell cytoplasm
accumulations of immune cells which
are visible to the unaided eye as white
oval-shaped regions. These are known
as Peyer’s patches. They are present in
the lamina propria and may extend into
the submucosa and are restricted to the
gut wall opposite to the attachment site
of the peritoneal membranes.
Large intestine
The large intestine comprises the colon,
appendix, rectum and the upper part of
the anal canal (Fig. 12.1). Its structure
Fig. 12.15 Large intestine, upper region of intestinal glands. An arrow shows the entrance to an
largely conforms to the general plan intestinal gland. Goblet cell cytoplasm is stained blue/turquoise. Special stain. High magnification.
(Fig. 12.2). The mucosa is similar along
the length of the large intestine, and Lumen of large intestine
goblet cells (Figs 12.15 and 12.16) are far
more common than in the small intes- Columnar epithelial cells
tine. The mucosal epithelium dips into
the mucosa and forms intestinal glands
which reach the muscularis mucosae
(Fig. 12.16). This arrangement increases
the area of interface between the luminal
contents and the epithelial cells. Colum-
nar epithelial cells, absorbing mainly
water, are present mainly on or near the
luminal surface, and stem cells and a Connective tissue lamina propria
few neuroendocrine cells are also
present in the epithelium. Villi and sub-
mucosal glands are not present in the
large intestine.
The muscularis externa of the large
intestine differs from the general plan in
that although it has an inner circular
layer its outer longitudinal layer is
arranged in three bands (taeniae coli).
Peristaltic contractions of the muscula-
ris externa move the contents in the
lumen towards the anus. Although
the large intestine is much shorter than
the small intestine, the transit time
through the large intestine takes rela-
tively longer at up to about 48 hours.
During transit, water and salt absorp-
tion occurs and the remnants form Muscularis mucosae
feces. The mucus secreted by goblet
cells in the epithelium is important in
lubricating the movement of feces along Submucosal connective tissue
the large intestine.
Fig. 12.16 Large intestine, intestinal glands and muscularis mucosae. Goblet cell cytoplasm is
stained turquoise/blue. Special stain. Low magnification.
Appendix
The appendix is a blind-ended tube con- Clinical notes
nected to the colon. It is similar in struc- Chemotherapy Many chemotherapy drugs used to treat cancer
ture to the large intestine and lymphoid target and kill cells in mitosis. As well as killing rapidly dividing
tissue is a prominent feature (Fig. 12.17). cancer cells these drugs kill normal dividing cells such as those in epithelia
Lymphoid tissue may extend between lining the small (and large) intestine. Normally, intestinal epithelial cells are
the muscularis externa and the luminal replaced every few days. After this type of chemotherapy there is impaired
surface, replacing the submucosa and replacement of the columnar cells and goblet cells in the intestinal epithelia.
the mucosa. The lymphoid tissue is As a result, absorption of nutrients and water is impaired and usually
most prominent in children, and largely diarrhoea occurs.
disappears in adulthood as the appendix Appendicitis The appendix is a blind-ended tube which may become
atrophies. inflamed due to stagnation and impaction of the contents of the gut. This
results in appendicitis. If the inflammation destroys the wall of the appendix
Liver it spreads into the peritoneal cavity. As a result, microorganisms from the
gut enter a large potential space where they can readily multiply: this may
The liver is a large, highly vascular, glan- be fatal.
dular structure situated in the upper
abdomen. It has significant roles in the
function of the digestive system. It is
covered by a connective tissue capsule
and, in turn, by peritoneum. The cell
type which forms the majority of the
parenchyma of the liver is the hepato-
cyte (Fig. 12.18). The liver receives blood
drained from most of the gastrointesti- space of Disse. The hepatocytes adjacent the basis of the functional unit. Hepato-
nal tract. This brings products of diges- to the space of Disse take up the small cytes closest to where hepatic arteries
tion, principally amino acids and mono- molecules produced by digestion and and hepatic portal veins (in portal tracts)
saccharides, directly from the gut. synthesise larger molecules required by open into sinusoids are exposed to the
Hepatocytes synthesise a range of large the body. Blood drains from sinusoids highest concentrations of oxygen and
molecules, some of which they store, into small veins, known as central veins molecules absorbed from the gut. These
e.g. glycogen; others they secrete into (Fig. 12.18), which join together and include the small molecules produced
blood, e.g. albumin. Hepatocytes also leave the liver as the hepatic vein. by digestion and any ingested toxic mol-
break down absorbed harmful mole- Between adjacent hepatocytes there ecules or harmful microorganisms.
cules (e.g. alcohol) and waste molecules are very small spaces, bile canaliculi Conversely, hepatocytes closest to
(e.g. from the breakdown of haemo- (Fig. 12.19). These channels receive bile central veins draining the sinusoids are
globin). Some waste molecules are secreted by hepatocytes. The direction exposed to lower levels of all these sub-
secreted by hepatocytes into bile (see of flow in bile canaliculi is opposite to stances. Hepatocytes in different regions
below), which drains into the duode- the blood flow in sinusoids. Bile canal- may appear similar but, in varying
num, from where they are eventually iculi join together and drain into a nutritional states and pathological con-
excreted in feces. network of epithelium-lined bile ducts. ditions, their appearance may depend
The liver receives blood from two The bile ducts pass through the liver on their position in relation to blood
sources: the hepatic artery, which sup- alongside branches of the hepatic arter- supply.
plies blood that is high in oxygen ies and hepatic portal veins in structures
content, and the hepatic portal vein, known as portal tracts (Figs 12.18 and
which supplies blood that is low in
Gall bladder
12.20). The ducts join together and
oxygen content. The hepatic portal vein eventually bile drains into a single Ducts draining bile from the liver even-
drains blood from the gastrointestinal duct which transports bile, via the gall tually drain into a single bile duct which
tract and carries the molecules produced bladder, to the duodenum. Bile aids the drains into the gall bladder. The gall
by digestion to the liver. These two digestion of fats as well as being the bladder lies on the right, close to the
sources of blood pass into liver sinu- route by which the breakdown products liver, and stores and concentrates bile
soids (wide vascular channels) lined by from the destruction of red blood cells prior to its release. The gall bladder is
irregularly placed endothelial cells lying are excreted. lined by a simple columnar epithelium
on an incomplete basement membrane. The classical functional unit of the which absorbs fluid and concentrates
Non-migratory macrophages, known as liver is a hexagonal lobule enclosed by the bile by up to 20 times. Smooth
Kupffer cells, are interspersed between connective tissue. In humans, connec- muscle forms the majority of the wall of
the endothelial cells and they phago- tive tissue is sparse between lobules but the gall bladder and its contraction helps
cytose effete red cells (and microorgan- is present in portal tracts supporting to expel stored bile. Parasympathetic
isms if present in the blood). Columns branches of the hepatic artery, hepatic nerves and molecules produced by
of hepatocytes lie alongside the sinu- portal vein and bile duct (Figs 12.18 and neuroendocrine cells in the duodenum
soids separated from the basement 12.20) and around central veins (Fig. control the flow of bile in relation to
membrane by a space (the space of 12.18). A fine meshwork of reticulin the contents of the gastrointestinal tract.
Disse) (Fig. 12.19). Blood passes along fibres supports the sinusoids (see Fig. Bile expelled from the gall bladder
the sinusoids and some plasma passes 4.3). From a functional view, it is appro- enters the common bile duct, which
between the endothelial cells into the priate to consider the blood supply as drains into the duodenum.
Fig. 12.17 Appendix. Special stain. High

magnification.
Lumen of appendix
Columnar epithelial cells
Lymphocytes (GALT)
Fig. 12.18 Liver, portal tract and central

vein. The lumen of the artery and the bile duct
in the portal tract are very small and difficult to
distinguish at this magnification, but the artery is
Red blood cells in central vein
closest to the hepatic portal vein in this figure.
Connective tissue is stained green and red blood
cells scarlet. Special stain. Very low magnification.
Sinusoids
Hepatocytes
Red blood cells in sinusoid
Lumen of hepatic portal vein in

portal tract
Fig. 12.19 The arrangement of hepatocytes,

sinusoids, the space of Disse and a bile
canaliculus.
Incomplete basement Hepatocytes Space of

membrane Disse
Blood Blood
Sinusoidal
endothelium
Bile Reticulin
canaliculus fibres
Fig. 12.20 Liver, portal tract. Connective

tissue and red blood cells are stained blue.
Special stain. High magnification.
Lumen of hepatic portal vein
Hepatocyte nuclei
Red blood cells

Endothelial cell nuclei
Lumen of sinusoid
Lumen of arteriole (branch

of hepatic artery)
Lumen of bile duct

Pancreas
Clinical note
Cirrhosis of the liver Hepatocytes are exceptionally efficient The pancreas lies in the abdominal
at repairing themselves by undergoing mitosis and replacing cavity and functions as an exocrine and
hepatocytes lost by damage (or surgery). However, some viruses and alcohol endocrine (Chapter 14) gland. It has a
can slowly and progressively alter the normal structure of the liver, and thus thin connective tissue capsule and is
its function. Many collagen fibres may be deposited and the normal divided into lobules by connective tissue
relationship of blood vessels, bile canaliculi and hepatocytes destroyed and septa. The exocrine cells are columnar
cirrhosis occurs. Bile excretion is reduced and bile pigments accumulate in epithelial cells (Fig. 12.21) arranged as
blood. The person appears yellow and death may be the result. acini or tubules and they secrete bicar-
bonate ions (which help neutralise
gastric acid) and pancreatic enzymes
(proteinases, peptidases, lipases and
amylases), which are inactive until they
Red blood cells in vessel reach the duodenum. The enzymes are
stored in zymogen granules in the apical
portions of the columnar cells; the
nucleus and rough endoplasmic reticu-
lum are in the basal portions of the cells
(Fig. 12.21). The release of secretions is
Cytoplasm of exocrine cells controlled by parasympathetic nerves
and molecules secreted by neuroendo-
crine cells in the duodenum. A duct
drains each acinus. Ducts join together
Nuclei of exocrine cells within the lobules and eventually all join
and form a single pancreatic duct. The
duct system is lined by epithelial cells
which, in the larger ducts, may be a
Nucleus of columnar epithelial cell double layer of columnar epithelial cells.
lining duct The pancreatic duct joins the bile duct
and bile and pancreatic juices drain into
Lumen of duct the duodenum.
Fig. 12.21 Pancreas, exocrine cells and part of a duct. The eosinophilic cytoplasm is due to the
proteins in the apical regions of the exocrine cells, and the basal, bluish cytoplasm, adjacent to the
nuclei and stained with haematoxylin, is due to rough endoplasmic reticulum. High magnification.
Summary
The digestive system
■ The digestive system consists of the alimentary canal connecting the mouth to the anus and associated structures, e.g. salivary glands, liver
and pancreas.
The alimentary canal

■ The alimentary canal has a general pattern of four layers:
■ a mucosa comprising an epithelium, basement membrane, lamina propria and a smooth muscle layer (the muscularis mucosae)
■ a submucosal layer supporting large blood vessels and nerves
■ a muscularis externa comprising an inner circular and an outer longitudinal layer of smooth muscle which contracts and moves the
contents of the canal towards the anus
■ an outer covering which is a serosal (peritoneal) membrane in most regions.
Oesophagus
■ The oesophagus is lined by a stratified squamous epithelium and has serous and mucous glands in the submucosal layer.
■ It has striated voluntary muscle in the muscularis externa in regions close to the mouth and smooth muscle in lower regions.
■ It has an outer adventitia binding it to adjacent structures.
Stomach
■ The stomach is lined by a simple epithelium. Cells lining gastric pits secrete mucus; cells lining gastric glands (in the main part of the
stomach) secrete acid and enzymes.
■ It has three layers of smooth muscle in its wall and an outer serosal layer.
Small intestine
■ Epithelia covering villi and lining intestinal glands comprise columnar absorptive cells, goblet cells, stem cells and Paneth cells.
■ In the duodenum submucosal glands secrete alkaline mucus into the lumen.
■ In the ileum lymphoid follicles are usually present.
Large intestine
■ A simple epithelium lines intestinal glands and contains absorptive columnar and goblet cells (no villi are present).
Structures associated with the digestive system

■ Salivary glands contain serous and mucous cells.
■ The tongue is covered by a stratified, squamous epithelium which, on its upper surface, has papillae and taste buds. Mucous and serous
glands and lymphoid cells are deep to the epithelium and skeletal muscle forms the inner mass of the tongue.
■ The liver is formed mainly of hepatocytes:
■ it receives blood draining most parts of the alimentary canal and synthesises many new molecules and stores glycogen
■ it secretes bile which drains into the duodenum and aids digestion of fats
■ it destroys red blood cells and excretes some waste molecules in bile.
■ The pancreas is formed mainly by exocrine cells (endocrine cells are also present):
■ pancreatic enzymes (inactive when secreted) drain into the duodenum, where they begin to digest carbohydrates, proteins and lipids.
97
Chapter 13
The urinary system
The urinary system consists of paired former is important in regulating blood tubules may be distinguished in histo-
kidneys and the urinary tract, which pressure and the latter in stimulating logical sections even at low magnifica-
comprises paired ureters, a urinary the formation of red blood cells. tion (Fig. 13.3). In humans, the medulla
bladder and a urethra (Fig. 13.1). Urine projects centrally as several pyramids
is produced by the kidneys and passes and the cortex extends as columns
Kidneys
along the ureters to the urinary bladder, between the pyramids (Fig. 13.2). The
where it is stored until it is voided via The gross structure of a kidney is best apices of the pyramids project as renal
the urethra. The route taken by urine described as seen in a longitudinal hemi- papillae into urine-filled spaces (minor
along the urethra to the exterior is an section (Fig. 13.2). Facing towards the calyces). Urine drains from tubules in
independent closed system in females, mid-line of the body, each kidney has the medulla into the calyces. Each minor
but is shared with the reproductive an indentation forming a hilum. At calyx drains urine into major calyces
system in males (Chapter 15). the hilum blood enters and leaves each that together form the renal pelvis. The
The urinary system is essential in kidney in, respectively, a renal artery relatively large, fluid-filled space of each
maintaining the homeostasis of the and a renal vein, and urine drains into renal pelvis drains into a ureter (Fig.
body. It does this by regulating the water a ureter. 13.2). Fat cells surround the renal pelvis,
and mineral salts in, and the acid–base The gross appearance of the kidney the ureter and vessels at the hilum of
balance of, blood. It is particularly displays an outer and an inner region, the kidney and pack a space known as
important in excreting toxic molecules the cortex and the medulla. The cortex the renal sinus. A dense layer of fat
containing nitrogen (e.g. urea and creati- has a granular appearance due to the surrounds each kidney.
nine) produced by the breakdown of presence of spherical structures about The blood supply to kidneys ensures
endogenous proteins. The urinary 200 μm in diameter known as renal that the whole volume of blood in the
system also ensures that useful mole- corpuscles. These corpuscles filter blood body passes through the kidneys every
cules in blood, e.g. proteins and carbo- in the initial stage in the formation of 5 minutes or so. The arrangement of
hydrates, are not lost during the urine. The cortex also contains convo- blood vessels is based on supplying (and
formation of urine. The toxic molecules luted tubules involved in forming urine. draining) each medullary pyramid and
and excess ions, dissolved in water, leave Renal corpuscles are not present in its associated cortical tissues separately,
the kidneys as urine, which passes along the medulla and the medulla appears a unit described as a renal lobe. (The
the urinary tract before being voided at smooth or may show striations. Straight human kidney is multilobar, but uni-
micturition. In addition, the kidneys and arching tubules are present in the lobar kidneys occur in many species.)
produce and secrete into blood two mol- medulla and they also are involved in Each renal artery branches and forms
ecules, renin and erythropoietin. The forming urine. Renal corpuscles and interlobar arteries. In turn, interlobar
Kidney Cortex
Fat surrounding
connective tissue
capsule of kidney
Renal pelvis
Fat in renal sinus
Calyx
Ureter Renal artery
Renal vein
Apex of medullary
pyramid
Medullary pyramid
Ureter
Collecting ducts
Urinary (and other straight
bladder tubules in
medullary rays)
Urethra
Fig. 13.1 The components of the urinary Cortex
tract. Fig. 13.2 A longitudinal section through a kidney. Arrows show the direction of flow of urine.
Cortex
Renal corpuscles Arcuate
artery
Medulla
Interlobar
Medullary ray artery
Blood vessel Apex of

medullary
pyramid
Junction of cortex and medulla Pyramid of medulla
(approximately)
Glomerulus
Fig. 13.4 The arrangement of arteries

supplying glomeruli in the kidney.
Medullary tubules sectioned

transversely
arteries branch further and then form
arcuate arteries which arch between
the cortex and medulla (Fig. 13.4).
Branches from arcuate arteries eventu-
ally supply each renal corpuscle with
an afferent arteriole. This arrangement
is essential in filtering the blood (see
Medullary tubules sectioned below) as well as supplying oxygen and
longitudinally nutrients.
Each afferent arteriole divides within
a renal corpuscle into capillaries, known
as glomerular capillaries (Fig. 13.5), and
these drain from the corpuscle into
Fig. 13.3 Kidney, cortex and medulla. The approximate junction between the cortex and medulla an efferent arteriole (Fig. 13.6). This
is shown (renal corpuscles are not present in the medulla). Connective tissue is sparse and stained blue. arrangement of capillaries draining to
Special stain. Very low magnification. an arteriole is unique to the kidney and
results in a relatively high blood pres-
sure in glomerular capillaries (Fig. 13.5)
which aids the filtration of blood. Effer-
ent arterioles divide and form a second
network of capillaries. Some of these
capillaries are straight vessels, vasa recta,
Surface of kidney
which lie between straight tubules in the
kidney whereas others form an exten-
Glomerular capillaries in renal sive meshwork surrounding convoluted
corpuscles tubules in the cortex (Fig. 13.6). The
second set of capillaries supplies oxygen
and nutrients to the cells of the kidney
and is also involved in modifying the
filtrate and forming urine. Veins drain
capillaries (other than glomerular capil-
Capillaries in cortex
laries) in the kidney and the routes they
take closely follow the arterial pattern.
Nephrons and collecting ducts

A nephron is the functional unit of the
Capillaries in medulla kidney (Fig. 13.6) and there are about
a million in each kidney in humans. A
nephron consists of a renal corpuscle,
which filters blood, and the uriniferous
tubule attached to it which drains and
Fig. 13.5 Kidney. Large branching blood vessels are shown supplying glomerular capillaries in renal modifies the filtrate. Eventually, the mod-
corpuscles in the cortex. The network of capillaries in the cortex and medulla is also displayed. Special ified filtrate becomes urine and drains,
procedure showing blood vessels. Very low magnification. via collecting ducts, into the renal pelvis.
The urinary system 99
Proximal basement membranes) form the filtra-

Tubular pole convoluted tion barrier between the blood and the
tubule
Glomerular capillaries filtrate. The space between the inner and
outer layers of the capsule receives the
Afferent arteriole
filtrate and is known as the urinary
Vascular pole
space (Fig. 13.7) even though the filtrate
Efferent arteriole
Distal is not yet urine.
Bowman’s capsule
convoluted Each Bowman’s capsule has two poles,
tubule
and it is extremely rare to see all the
Cortex Proximal features of each pole in any one (histo-
convoluted
tubule logical) section of a corpuscle.
Collecting
duct ■ Vascular pole (Figs 13.6 and 13.7). At
Loop of this pole an afferent arteriole enters
Henle each renal corpuscle, branches and
forms glomerular capillaries. These
capillaries rejoin and drain into an
efferent arteriole (not a venule),
Vasa recta which leaves the corpuscle at the
vascular pole.
Loop of
Henle ■ Tubular pole (Figs 13.6–13.8). At this
Vasa recta
Arcuate artery pole the filtrate drains from the
Medulla and vein urinary space of the renal corpuscle.
It enters the proximal part of the
uriniferous tubule, which extends
from the parietal layer of Bowman’s
capsule at this pole.
Renal pelvis
Fig. 13.6 The structure of a nephron (renal corpuscle and uriniferous tubule) and related Filtration
blood vessels. Blood in glomerular capillaries is fil-
tered through the endothelium lining
the capillaries. It then traverses the fused
basement membranes of the endothe-
Arteriole at lium and of the adjacent podocytes (the
vascular pole
visceral epithelial cells of Bowman’s
Blood cells in capsule) (Fig. 13.9).
glomerular
capillary Filtration is affected by:
■ the pressure of blood in the afferent

Urinary space
arteriole
■ the pressure of blood in the efferent
Blood cells in
capillary arteriole; this provides resistance to
the outflow of blood from the
Nucleus of
glomerular capillaries causing a
squamous
epithelial cell relatively high pressure in the
(outer layer of glomerular capillaries
Bowman’s capsule) ■ fenestrations in the endothelium of
the glomerular capillaries; these
fenestrations retain molecules over
Lumen of proximal
about 69 000 daltons in the blood
convoluted tubule (e.g. albumin)
■ the fused basement membranes;
Fig. 13.7 Kidney, renal corpuscle, vascular and tubular poles. Although an afferent and an these are charged and repel many
efferent artery, respectively, supply and drain glomerular capillaries via the vascular pole, only one protein molecules
arteriole is apparent in this section. The arrow shows the tubular pole where filtrate in the urinary space
■ the structure of the podocytes.
drains into the proximal tubule. High magnification.
Podocytes have numerous large and
small cytoplasmic foot processes
Renal corpuscles squamous epithelial cells (Fig. 13.7) and (Figs 13.9 and 13.10). The smaller
Each renal corpuscle consists of glomer- it is continuous with the inner visceral foot processes abut the basement
ular capillaries (a renal glomerulus) (Fig. layer of epithelial cells. The cells of the membrane and there are small
13.5) within a Bowman’s capsule. The inner layer, known as podocytes, have spaces between them. It is probable
capsule is shaped like a hollow, double- numerous cytoplasmic processes which that this arrangement of the foot
walled cup (Fig. 13.6) and it is lined abut the capillaries of the glomerulus. processes is involved in preventing
by epithelial cells. The outer parietal The endothelial cells lining the capillar- some proteins from passing from
layer of Bowman’s capsule is lined by ies and the podocytes (and their fused blood into the filtrate.
Proximal convoluted tubule (lumen)
Blood cells in vessel
Bowman’s capsule of renal corpuscle
Proximal convoluted tubule (lumen)
Urinary space
Blood cells in glomerular capillary
Fig. 13.8 Kidney, renal corpuscle, tubular pole and the initial part of the draining proximal tubule. The arrow shows the tubular pole where
filtrate from the urinary space drains into the proximal tubule. This section along some of the length of the proximal tubule displays the first part of its
convoluted course, in the plane of the section. The vascular pole of the corpuscle is not in the plane of this section. High magnification.
Red blood cells
Podocyte nucleus
Lumen of glomerular
capillary
Podocyte foot
processes (large)
Lumen of glomerular
capillary
Podocyte foot processes (small)

Fig. 13.9 Kidney, podocytes and glomerular capillaries. Electron micrograph. The filtration barrier between blood in glomerular capillaries and the
urinary space which drains the filtrate is thin. The complexity and the size of the cytoplasmic foot processes of podocytes adjacent to the outer wall of the
capillaries are shown. Some regions of the filtration barrier are shown between asterisks. Low magnification.
of the sodium and chloride ions. This

resorption is facilitated by microvilli on
the apical (luminal) surfaces of the epi-
thelial cells lining the proximal tubules,
providing a large interface between
the cell membrane and the filtrate. The
movement of sodium ions out of the
filtrate is an energy-dependent process
powered by mitochondria in the epithe-
lial cells. Water passively follows the
sodium ions.
Resorbed water and ions readily pass
into blood in the capillaries, which form
a meshwork around proximal convo-
luted tubules (Figs 13.7, 13.8 and 13.11).
The movement of these ions and water
helps maintain electrical neutrality and
osmotic equilibrium in the capillaries.
Amino acids and glucose in the glomer-
ular filtrate are resorbed from the filtrate
in proximal tubules and return to blood.
Small proteins in the filtrate are taken
into the epithelial cells lining proximal
tubules by endocytosis. After fusion of
the endocytotic vesicles with lysosomes
the proteins are digested and the amino
acids produced return to blood.
In addition, the epithelial cells lining
proximal tubules (in humans) are able
to secrete waste molecules such as creat-
inine into the lumen of the proximal
tubules, and they are able to prevent the
resorption of some toxins and drugs
which have passed from blood into the
glomerular filtrate.
Podocyte showing three foot processes (large)
Fig. 13.10 Kidney, podocytes. Electron micrograph. This scanning view looks at podocytes as Loop of Henle
though from the urinary space. Arrows (white) indicate large cytoplasmic processes extending from The tubule of the first part of a loop
one podocyte. Numerous smaller cytoplasmic processes (arrowheads) wrap around the glomerular of Henle drains a proximal convoluted
capillaries. Low magnification. tubule and it passes (descends) as a
straight tubule towards, and usually
into, the medulla. The tubule then loops
The filtrate passing out of blood and into and continues as a distal convoluted and passes (ascends) as a straight tubule
the urinary space of Bowman’s capsule is tubule which eventually drains into a into the cortex (Fig. 13.6). The lower
known as the glomerular filtrate and it straight collecting duct in the cortex (Fig. part of the descending limb of the loop
flows at a rate of about 190 litres/day, of 13.6). (Collecting ducts are not usually of Henle and some of the ascending
which 188.5 litres is reabsorbed as it passes described as part of the nephron.) limb are tubules that have relatively
along the uriniferous tubules and collect- wide lumina and thin walls. These ‘thin’
ing ducts. As a result approximately 1.5 Proximal convoluted tubule regions are lined by a simple squamous
litres of urine are excreted per day. Proximal convoluted tubules are longer epithelium (Fig. 13.12). The final portion
than distal convoluted tubules and thus of the loop of Henle is lined by a simple
Uriniferous tubule are the predominant tubule seen in cuboidal epithelium and it continues, in
Each uriniferous tubule drains the fil- histological sections of the kidney cortex the cortex, as a distal convoluted tubule
trate from the urinary space of a Bow- (Fig. 13.11). They are lined by simple which is lined by a similar cuboidal
man’s capsule (Fig. 13.6). The filtrate cuboidal (or low columnar) epithelial epithelium.
enters the proximal convoluted tubule, cells (Figs 13.7 and 13.8). The lumen of The functions of the various regions
the first part of the uriniferous tubule, proximal tubules is indistinct in many of loops of Henle are related to produc-
and this takes a coiled course in the histological sections as the lumen that ing a hypertonic environment in the
cortex before straightening. This straight transports filtrate in life is virtually filled sparse connective tissue (interstitium)
tubule continues and forms a loop (the by the apical surface of the epithelial between tubules in the medulla (Fig.
loop of Henle), which extends from the cells. 13.3). This is essential for the produc-
cortex towards the medulla; many loops Proximal convoluted tubules resorb tion of hypertonic urine (see below).
of Henle extend deep into the medulla. about 80% of the water that has passed The interstitium comprises few cells,
Each loop of Henle returns to the cortex into the glomerular filtrate and many e.g. fibroblasts, sparse fibres and complex
carbohydrate molecules. Several factors (Fig. 13.6). Collecting ducts are straight the hypertonic interstitium. This aids
are involved in modulating the tonicity tubules which lie clustered in parallel resorption of water and the production
of the interstitium: with other straight tubules (e.g. loops of of hypertonic urine. Two hormones are
Henle) that pass between the cortex and involved in controlling this resorption of
■ the descending thin limb of the loop
the medulla. The regions containing water and some ions. Aldosterone stim-
of Henle is freely permeable to
parallel tubules are known as medullary ulates the epithelial cells lining collect-
sodium and chloride ions and water
rays (Fig. 13.3). Collecting ducts are ing ducts to resorb sodium and chloride
■ the majority of the (cuboidal)
lined by a simple cuboidal epithelium ions, and water follows passively. In
epithelial cells lining the ascending
and in the medulla are surrounded by addition, antidiuretic hormone (from
limb is impermeable to water
■ cuboidal epithelial cells lining the
ascending limb actively pump sodium
ions into the interstitium and chloride
ions follow passively; the hormone
aldosterone from the adrenal glands Proximal convoluted tubule
(Chapter 14) stimulates this
resorption of sodium ions
■ some ions in the interstitium diffuse
into nearby straight capillaries (vasa Renal corpuscle
recta) (Fig. 13.12)
■ some ions re-enter the descending
limb but may be pumped out again
as they pass again along the distal
(ascending) limb
■ the net movement of ions results in:
■ a hypertonic interstitium
(particularly near the apex of the
medullary pyramids)
■ a hypotonic fluid passing into the
distal tubule in the cortex.
Distal convoluted tubule
The term ‘countercurrent multiplier
mechanism’ is used to describe this
complex movement of ions.
Distal convoluted tubule

Distal convoluted tubules are shorter
than proximal convoluted tubules so Fig. 13.11 Kidney, cortex. Renal corpuscles, proximal and distal convoluted tubules. This stain shows
appear to be fewer in number in histo- red blood cells as scarlet and their location is readily seen even at this low magnification. Special stain.
logical sections (Fig. 13.11). They are Low magnification.
lined by a simple epithelium consisting
of small cuboidal or low columnar cells
(Fig. 13.13) which do not have microvilli.
As a result, in comparison with proximal
tubules, distal tubules appear to have
more distinct lumina and more closely
packed cells in their walls (Fig. 13.13). Lumen of loop of Henle (thin limb)
Each distal convoluted tubule returns
to the vascular pole of the renal corpus-
cle from which it arose and forms part
of a functional unit known as the juxta-
glomerular apparatus (see below). Epi-
thelial cells lining distal tubules resorb
sodium ions from the filtrate. Resorbed
molecules return to blood in nearby cap- Red blood cells in vasa recta
illaries (Fig. 13.11). In addition, hydro-
gen ions are secreted. The ion movements
in this region are important in regulat-
ing the tonicity and acid–base balance of
blood. The movements of these ions are
affected by the hormone aldosterone
Lumen of tubule lined by cuboidal
from the adrenal gland (Chapter 14). epithelium
Collecting ducts
Several distal convoluted tubules in the Fig. 13.12 Kidney, medulla, vasa recta and tubules sectioned along their length. This stain
cortex drain into each collecting duct shows red blood cells as scarlet. Special stain. Medium magnification.
(Figs 13.14 and 13.15). These epithelial

cells probably detect changes in sodium
Bowman’s capsule concentration in the filtrate from that
corpuscle and help control the rate of
filtration by affecting renin secretion.
Urinary space Connective tissue within, and adjacent
to, the renal corpuscle is known as
Renal corpuscle mesangial tissue and it is sparse. Mesang-
ial cells around glomerular capillaries
and in the region of the juxtaglomerular
Lumen of proximal tubule apparatus are able to contract and may
affect blood flow in the region. In
addition, they have phagocytic functions
which may be involved in maintaining
the basement membranes filtering the
blood. Erythropoietin, a molecule which
stimulates the production of red cells by
Lumen of distal tubule bone marrow, is produced by kidneys
and it is possible that mesangial cells are
the source of this hormone.
Urinary tract
Fig. 13.13 Kidney, cortex. Connective tissue is stained blue. Special stain. High magnification. Renal pelves and ureters
Urine drains from the ducts of Bellini in
the medulla of each kidney into the
lumen of the pelvis of the kidney. The
Lumen of proximal renal pelves are lined by transitional epi-
tubule draining this thelium, the specialised layered epithe-
corpuscle
lium (urothelium) lining all the urinary
Podocytes
Glomerular capillaries adjacent to tract. Each pelvis narrows and is contin-
glomerular uous with a ureter (Fig. 13.2).
capillaries
Flow of filtrate in The wall of each ureter is formed
Urinary space uriniferous tubule from three layers (Fig. 13.16):
Squamous epithelium ■ An inner lining mucosa. The mucosa

of Bowman’s capsule comprises the transitional
epithelium lining the lumen and the
Efferent arteriole Afferent underlying, supporting connective
arteriole
tissue. This specialised epithelium
Epithelial cells forming
the macula densa prevents excess ions and toxic
Distal tubule draining from
this corpuscle molecules in hypertonic urine from
Flow to diffusing from the urine through the
collecting duct Cells synthesising renin epithelium and returning to circulate
Mesangial cells in blood.
Fig. 13.14 The juxtaglomerular apparatus. Arrows indicate direction of flow of filtrate. ■ A middle muscularis layer. The
muscularis is composed of an outer
longitudinal and an inner circular
the posterior pituitary gland; see Chapter connective tissue. In addition, a short layer of smooth muscle in the upper
14) controls the permeability of the cells region of the distal tubule of the urinif- two-thirds of the ureter. In the lower
lining collecting ducts and regulates the erous tubule draining filtrate from that third, there is an additional outer
amount of water lost in urine. Collecting corpuscle and lying adjacent to the vas- layer of smooth muscle that spirals
ducts join together and form wider cular pole, is also involved in the juxta- around the long axis of the ureter.
ducts (of Bellini) which drain the urine glomerular apparatus. The muscularis layer undergoes
into minor calyces at the medullary Cells in the wall of afferent arterioles peristaltic contractions and propels
papillae, and thence into the major secrete the hormone renin. Via its effects urine along the ureter towards and
calyces of the renal pelvis. on the liver and lungs, renin controls the into the bladder.
production of a molecule (angiotensin) ■ A thin connective tissue covering. The
Juxtaglomerular apparatus which in turn stimulates the production outer connective tissue covering
Each juxtaglomerular apparatus (Fig. of aldosterone by the adrenal glands holds each ureter against the
13.14) involves an afferent arteriole sup- (Chapter 14). The epithelial cells lining adjacent posterior abdominal wall
plying blood to glomerular capillaries in the distal tubule at the vascular pole and separates them from overlying
a renal corpuscle, the efferent arteriole appear to be packed together. This peritoneum (the serous membrane
draining these capillaries and adjacent region is known as the macula densa of the peritoneal cavity).
Urine drains along each ureter and

into the urinary bladder. Both ureters
pass obliquely through the wall of the
Macula densa region of distal bladder and this helps prevent back flow
tubule of urine into the ureter
Urinary bladder
Lumen of proximal tubule The urinary bladder is similar to the
ureters in that its wall comprises three
layers: a mucosa, a muscularis and an
outer layer. However, the bladder is able
Urinary space of renal corpuscle
to distend and store large quantities of
urine and, after infancy, it is able to con-
tract and expel urine at socially accepta-
Bowman’s capsule ble times.
The bladder mucosa is composed
of transitional epithelium (urothelium)
and a supporting connective tissue
lamina propria (Fig. 13.17). The mucosa
is folded and forms rugae in an empty
bladder and there are several layers of
Fig. 13.15 Kidney, cortex, renal corpuscle, macula densa of the distal tubule. High
cells in the epithelium; some surface
magnification.
cells may appear domed (Fig. 13.17). In
addition, in the empty bladder parts of
the cell membrane of surface epithelial
cells are drawn into the cytoplasm. As
Connective tissue covering ureter the volume of urine stored in the bladder
increases the rugae unfold, the number
of cell layers in the epithelium decreases
and the epithelial cells are flattened and
their cell membranes lengthen. The epi-
Lumen thelium lining the bladder is imperme-
Connective tissue able and it ensures that hypertonic urine
does not equilibrate with surrounding
isotonic tissues and blood, and that toxic
Epithelium (transitional) molecules, e.g. urea, remain in urine and
are excreted.
The lamina propria of the bladder
mucosa connects the epithelium to the
Smooth muscle layers
muscularis layer, which is known as the
detrusor muscle. The smooth muscle
cells in the detrusor muscle are arranged
in three interlacing layers. Contraction
Fig. 13.16 Ureter, transverse section. Connective tissue is stained green. Special stain. Very low of the detrusor muscle is brought about
magnification. by stimulation of the muscle cells by
parasympathetic nerves which are under
conscious control after infancy. This
contraction empties the bladder as urine
is voided via the urethra. Parts of the
Connective tissue bladder are covered by peritoneum and,
as the bladder fills, it moves smoothly
Transitional epithelium against adjacent structures. Connective
tissue over other parts of the bladder
attaches it to adjacent structures.
Urethra
The urethra is a tube that carries urine
Surface epithelial cell (domed)
from the urinary bladder to the exterior.
In the male, it also shares reproductive
functions. Further details of the male
Lumen of urinary bladder urethra are given in Chapter 15. In
females, the urethra is a relatively short
tube and most is lined with a stratified
Fig. 13.17 Bladder, mucosa. High magnification. squamous epithelium.
Clinical note Clinical note

Glomerular disease An abnormally thickened basement Bladder cancer
membrane between the endothelial cells lining the glomerular Carcinogens (cancer-
capillaries and the podocytes causes one type of glomerular disease. Usually, causing substances) are widely
the thickened basement membrane allows molecules which are normally used in chemical industries,
retained in the blood to pass through the membrane and into the filtrate. particularly in those producing
Albumin normally is too big to pass into the filtrate but in glomerular dyes and rubber. Without due
disease it passes through in such large quantities that it is not resorbed fully care, people working in these
and thus appears in the urine. One cause of thickening of the basement industries are at increased risk of
membrane is the deposition of circulating antigen–antibody complexes on developing bladder cancer. The
the membrane. carcinogens and/or their
metabolites are excreted via the
kidneys, and the bladder
epithelium, exposed to high levels
of the carcinogens, undergoes
cancerous changes.
Summary
The urinary system
■ This consists of paired kidneys and the urinary tract (paired ureters, urinary bladder and urethra).
Kidneys
■ The kidneys comprise cortex and medulla.
■ The functional unit is the nephron, comprising the renal corpuscle and uriniferous tubule.
■ Renal corpuscles are present in the cortex:
■ an afferent arteriole supplies glomerular capillaries within each corpuscle and an efferent arteriole drains the glomerular capillaries
■ the glomerular capillaries are surrounded by a double-walled cup lined by epithelial cells
■ the inner layer of epithelial cells (podocytes) is closely applied to the endothelial cells lining the capillaries and they share basement
membranes:
■ filtration of blood occurs across the endothelial cells, basement membranes and podocytes
■ the filtrate enters the urinary space between the walls of the cup
■ the filtrate drains from the cup into a uriniferous tubule.
■ Each uriniferous tubule comprises an initial, convoluted proximal tubule (in the cortex), a straight looped portion (loop of Henle) extending
from the cortex and into the medulla and a distal convoluted tubule (in the cortex).
■ The low columnar epithelial cells lining proximal tubules absorb water, proteins and many of the filtered sodium and chloride ions.
■ Some of the cuboidal epithelial cells lining the loops of Henle actively pump sodium ions into the surrounding connective tissue, which
becomes hypertonic.
■ Cuboidal epithelial cells lining the distal tubules resorb sodium ions.
■ Some resorbed ions return to blood capillaries in the cortex and medulla.
■ Uriniferous tubules drain into collecting ducts.
■ Aldosterone and antidiuretic hormone control the amount of water and ions resorbed and the tonicity of urine, thus aiding homeostasis.
Ureters
■ Each transports urine from a renal pelvis to the urinary bladder.
■ They are lined by a mucosa consisting of a transitional (multilayered) epithelium and connective tissue:
■ the transitional epithelium ensures hypertonic urine does not equilibrate with isotonic tissue fluid and blood
■ They have smooth muscle layers which contract and pass the urine into the bladder.
■ They are attached by an outer layer of connective tissue to adjacent structures.
Urinary bladder
■ The urinary bladder has a mucosa and muscularis similar to the ureter but is able to store a large volume of urine. As urine is stored the
mucosa unfolds, the number of layers of epithelial cells is reduced and the epithelial cells flatten.
■ After infancy, parasympathetic nerves (under conscious control) stimulate contraction of the muscularis and this empties the bladder into the
urethra at micturition.
Urethra
■ It is short in females and lined by a stratified squamous epithelium.
■ It is longer in males and shared with the reproductive system.
106
Chapter 14
The endocrine system
The endocrine system comprises cells The endocrine organs comprise the ies in endocrine glands. This arrangement
which synthesise particular molecules pituitary gland, thyroid gland, parathy- facilitates the movement of molecules
and secrete them into blood vessels. roid glands, adrenal (suprarenal) glands from and to the capillaries.
This contrasts with exocrine secretions and the pineal gland. In addition, the
in which secreted molecules pass along pancreas contains clusters of endocrine
a duct system to their site of action, e.g. cells known as islets of Langerhans
from salivary glands to the mouth. The amongst the pancreatic exocrine cells
Hypothalamus and
particular molecules secreted by endo- (Chapter 12), the gonads contain cells
pituitary gland (hypophysis)
crine cells are known as hormones and secreting reproductive hormones (Chap-
the vascular circulation carries them ters 15 and 16) and secretions from The hypothalamus and pituitary gland
around the body where they interact endocrine cells in the hypothalamus function together (Fig. 14.1). The
with various cells described as target affect the secretory activities of the pitui- hypothalamus is the part of the brain
cells. The principal means by which hor- tary gland (see below). There are also connected by a stalk to the pituitary
mones achieve their specific action is small groups of neuroendocrine cells in gland. The hormones produced by the
by interacting with receptor molecules many other regions, e.g. in the epithelial hypothalamus and the pituitary affect
expressed by the target cells in various linings of the gastrointestinal tract. the function of many cells in different
tissues and organs. Once stimulated, Some are known as paracrine cells and parts of the body.
target cells respond in a variety of ways, their secretions act in surrounding The pituitary gland is situated in the
e.g. by increasing synthesis of certain areas. cranial cavity in a depression in the
molecules. Hormones may be steroids, All endocrine glands and endocrine sphenoid bone of the skull known as
peptides or proteins, or other molecules cells are well supplied by blood provid- the pituitary fossa. The pituitary has a
derived from amino acids. In general, ing the metabolites needed to synthesise secretory (glandular) and a neural com-
hormones are involved in regulating hormones. The capillaries in endocrine ponent called, respectively, the adeno-
metabolic activities in cells in many glands are fenestrated and most hor- hypophysis and neurohypophysis.
organs and tissues of the body, many mones are secreted directly into them. Connective tissue surrounds these two
of which are important in controlling A fine meshwork of reticulin fibres sup- components as a capsule. The compo-
homeostasis. ports most endocrine cells and capillar- nents differ in embryological origin,
Capillary bed in
Hypothalamus hypothalamus
(median eminence) TrH
Pars tuberalis
Neurons in the hypothalamus
Infundibulum secreting releasing hormones (rH)
Neurons in the hypothalamus
Portal veins in storing and secreting hormones
pituitary stalk in the hypophysis
Axons in posterior To hypothalamus Endocrine cells in the hypophysis
lobe of the pituitary secreting trophic hormones
Indicates stimulation of secretory
Stored hormone TSH activity
Indicates inhibition of secretory
Capillary bed activity
in anterior lobe
Pars nervosa of pituitary
Pars intermedia
Pars distalis
To hypophysis and
hypothalamus
Stimulates Thyroxine Thyroid gland
metabolism
Fig. 14.1 The structure of the pituitary gland (hypophysis) and its relationship to the hypothalamus. Only blood vessels involved in the portal
circulation are shown. An example of how feedback mechanisms affect the production of thyroid-releasing hormone (TrH) from the hypothalamus, thyroid-
stimulating hormone (TSH) from the pituitary gland, and thyroxine from the thyroid gland is shown.
The endocrine system 107
structure and function. The adenohypo- of the pituitary gland formed by the endocrine cells. The cytoplasm of
physis develops from oral ectoderm and neurohypophysis. These neurons chromophobes is virtually unstained
it has clusters or strands of secretory synthesise peptide hormones which with most dyes, and in some chromo-
(glandular) cells. The neurohypophysis pass along their axons. These phobes the cytoplasm is sparse (Fig.
develops from the part of the brain hormones are stored in the end 14.3). Other methods of staining cells of
which forms the hypothalamus. Nerve regions of the axons in the the pars distalis emphasise the differ-
axons are a prominent structural com- neurohypophysis before they are ences between the chemical composi-
ponent of the neurohypophysis and released into the vascular tion of their cells by specifically staining
hormones are released from the axons. system. the glycoproteins in basophils (Fig. 14.3).
The hormones secreted by the pitui- Immunohistochemical methods using
tary gland are dependent in two distinct Adenohypophysis light and electron microscopy have now
ways on hormones produced by cells in The adenohypophysis consists of three determined precisely which cells in the
the hypothalamus (Fig. 14.1). parts, the pars distalis (anterior lobe), pars distalis produce the various ante-
the pars intermedia and the pars tubera- rior lobe hormones.
■ Adenohypophysis and its vascular lis (Fig. 14.1). The cells of the pars dista- Hormones produced by the adenohypo-
connections (Fig. 14.1). A portal lis form several specific hormones (see physis are collectively termed trophic
system of capillaries connects the below). In humans, the pars intermedia hormones in that they stimulate the
hypothalamus, via the pituitary stalk, and pars tuberalis are relatively small release of other hormones from endo-
with the adenohypophysis. (The regions and their significance is not crine cells in endocrine glands or in other
definition of a portal system is two clear. regions. In general, each endocrine cell in
capillary beds connected by a set of The cells of the pars distalis have been the pars distalis produces only one type
veins; see hepatic portal system categorised by the reaction of their cyto- of trophic hormone. Some acidophils
Chapters 10 and 12.) Some plasm to various dyes. Cells that bind produce the protein somatotrophin,
hormones produced by neurons dyes are termed chromophils and those which is also known as growth hormone
in the hypothalamus are secreted that do not are categorised as chromo- (GH) as it is important in stimulating
into the first capillary bed in the phobes. In routine H&E preparations growth, particularly in bones. Other
hypothalamus. These capillaries some chromophils bind eosin and are acidophils produce the protein prolactin
drain into portal veins which carry known as acidophils; others bind hae- (PrL), a hormone which has a major
the hormones along the pituitary matoxylin and are known as basophils effect on milk production by the
stalk to the second capillary bed in (Fig. 14.2). The differences are due to mammary glands and is also known as
the adenohypophysis. By this route variations in the pH of the hormones mammotrophin. All basophils produce
hormones from the hypothalamus stored as cytoplasmic granules in the glycoproteins; some produce TSH and
interact specifically with endocrine
cells in the adenohypophysis and
control their secretion of a variety of
other hormones.
The hypothalamic hormones
Basophil cells
which pass in the portal system to
the adenohypophysis are peptides
and most stimulate specific cells
Basophil cytoplasm
in the adenohypophysis to release
their specific hormone. These
hypothalamic peptides are known
as releasing hormones (rH). For
example, the rH from the
hypothalamus that stimulates cells
in the adenohypophysis to release
their hormone which stimulates
the thyroid is known as thyroid- Acidophil cells
releasing hormone (TrH). The
pituitary hormone is known as
thyroid-stimulating hormone (TSH)
and it stimulates the thyroid gland
to secrete thyroid hormones, e.g.
thyroxine (Fig. 14.1). (In contrast,
a few peptide hormones from the
hypothalamus inhibit the release
of some hormones from the
adenohypophysis.) Acidophil cytoplasm
■ Neurohypophysis and its neural
connections (Fig. 14.1). Axonal
processes of some nerve cell bodies
in the hypothalamus extend along Fig. 14.2 Pituitary gland, anterior lobe (pars distalis) of the adenohypophysis. High
the pituitary stalk and into the part magnification.
Neurohypophysis
The neurohypophysis is described in
Acidophil cells three parts: the median eminence, the
infundibulum and the pars nervosa
(posterior lobe of the pituitary) (Fig.
Basophil cytoplasm
14.1).
■ Median eminence. This part of the

hypothalamus contains:
■ neurons that secrete the
hypothalamic releasing hormones
which regulate the secretory
activity of cells in the pars distalis
of the pituitary
■ the primary capillary bed of the
portal system which carries these
hypothalamic hormones to the
pars distalis
■ other hormone-producing
neuronal cell bodies which have
axons that extend along the
Chromophobe cells infundibulum to the pars nervosa.
■ Infundibulum. This is a continuation
of the hypothalamus along the
pituitary stalk.
Fig. 14.3 Pituitary gland, anterior lobe (pars distalis) of the adenohypophysis.
■ Pars nervosa. This is the region
Glycoproteins in the cytoplasm of basophil cells are stained purplish. The cytoplasm of acidophil cells is
stained orangey brown. Some chromophobes have palely stained cytoplasm, others appear to have where axons from neurons in the
very little cytoplasm. Special stain. High magnification. median eminence terminate (Fig.
14.4). Hormones synthesised by
these neuronal cell bodies pass
along their axons and are stored in
granules in swollen axon terminals,
known as Herring bodies, before
release. These axons are supported
by glial cells, called pituicytes. Two
hormones are released from the pars
nervosa. They are antidiuretic
hormone, which acts on the kidneys,
Nuclei of pituicytes and oxytocin, which acts on
mammary glands and the uterus.
Axons of hypothalamic neurons The effects of these hormones
are described in Chapters 13
and 16.
Thyroid gland
Fig. 14.4 Pituitary gland, posterior lobe (pars nervosa) of the neurohypophysis. Pituicytes and
axons. High magnification.
The thyroid gland lies anterior to the
lower part of the larynx and upper
trachea. It comprises two lobes that
others produce adrenocorticotrophic endocrine orchestra’ and this term has are connected across the mid-line by the
hormone (ACTH), which stimulate, also been applied to the hypothalamus. isthmus. The majority of the endocrine-
respectively, the thyroid gland and the They both have coordinating roles in secreting cells of the thyroid are arranged
cells in the cortex of the adrenal glands determining the function of many and as simple (single layered) epithelia sur-
(see below). Yet other basophils produce varied endocrine-secreting cells in the rounding roughly spherical spaces filled
two trophic hormones per cell, both cat- body. In turn, however, many hormones with colloid (Fig. 14.5). The colloid is
egorised as gonadotrophins as they affect produced by endocrine cells in endo- formed by thyroglobulin, an iodinated
endocrine secretion by cells in the gonads crine glands and in other organs in glycoprotein which is stored as the pre-
(ovaries and testes). The gonadotrophins the body are able to regulate the secre- cursor of active thyroid hormones.
are follicle-stimulating hormone (FSH) tory activity of cells in the hypothalamus These spheres, known as thyroid folli-
and luteinising hormone (LH). Further and/or the hypophysis that are cles, vary in size and virtually fill the
details of the function of FSH and LH are stimulating their own levels of hormone thyroid gland. Scattered amongst the
described in Chapters 15 and 16. production. This type of regulatory epithelial cells lining follicles, and in
The pituitary gland is sometimes mechanism is known as negative feed- between some follicles, a minor cell
referred to as the ‘conductor of the back (Fig. 14.1). population known as parafollicular (C)
Clinical note
Iodine deficiency Sea
Nuclei of follicle epithelial cells water is rich in iodine
salts and in some countries
supplements of iodine salts are
added to table salt. However, in
some parts of the world,
particularly those distant from a
salty sea, there may be insufficient
intake of iodine in the diet to
provide adequate levels of thyroid
Parafollicular cell nuclei hormones. In such cases, TSH
levels in blood increase, the
thyroid undergoes hypertrophy
and a swelling in the neck,
Colloid in follicles
known as a goitre, develops.
impulses and contraction of muscle.

Regulating the amount of calcium in
blood is essential for normal nerve and
Fig. 14.5 Thyroid gland. The thyroxine-secreting cells lining these follicles are very flattened and muscle function.
little cytoplasm is apparent. The parafollicular cells have pale staining cytoplasm. High magnification.
Parathyroid glands
cells is present (Fig. 14.5). Parafollicular ■ secretion of active thyroid
The parathyroid glands are small paired
cells secrete a peptide hormone, calci- hormones into capillaries.
structures on the posterior surface of the
tonin, which lowers blood calcium
Thyroxine is the major hormone thyroid gland. (There is usually more than
levels.
secreted by thyroid epithelial cells. Thy- one pair.) There are two major parenchy-
Extracellular storage of hormone pre-
roxine is derived from iodinated tyrosine mal cell types, chief cells and oxyphil
cursor molecules in follicles is unique to
molecules in thyroglobulin and is also cells (Fig. 14.6). Chief cells are relatively
the thyroid and involves the epithelial
known tetra-iodothyronine (T4). Thyrox- small and make and secrete parathyroid
cells lining the follicles in numerous
ine stimulates metabolism, particularly hormone (PTH). Oxyphil cells are larger
complex activities. The appearance of
of carbohydrates and lipids, and pro- and stain with dyes such as eosin; their
these epithelial cells depends on how
motes growth and development. role is not known. In adults, adipocytes
active they are. Less active or inactive
Thyroxine levels in blood are control- appear in the gland (Fig. 14.6).
cells are low, cuboidal or flattened and
led by mechanisms involving TrH from PTH assists in maintenance of
have few organelles. Active thyroid epi-
the hypothalamus and TSH from the calcium levels in the blood and in
thelial cells are columnar and have two
anterior lobe of the pituitary gland (Fig. body fluids, in conjunction with calci-
main functions; both can occur in the
14.1). A low level of thyroxine in blood tonin. Low levels of calcium in blood
same cell at the same time. They are:
stimulates the secretion of TrH and stimulate the secretion of PTH. Calci-
■ Formation and storage of TSH. The action of TSH on thyroid epi- tonin and PTH have opposite effects and
thyroglobulin. This involves: thelial cells stimulates the secretion of together affect the mineralisation of
■ synthesis of glycoproteins, which thyroxine into blood. When the level of bone via the activity of osteoclasts
are the precursors of thyroxine in blood is too high, negative (Chapter 9).
thyroglobulin feedback is activated and thyroxine,
■ uptake of iodide from blood acting on the hypothalamus and the
Adrenal (suprarenal) glands
■ exocytosis of the glycoproteins hypophysis, suppresses, respectively, the
into follicles levels of TrH and TSH secreted (Fig. The paired adrenal glands are adjacent
■ formation of thyroglobulin by 14.1). The consequence of this feedback to the superior surfaces of the kidneys
the iodination (of tyrosine is that secretion of thyroxine decreases in humans and are known as suprarenal
components) of the glycoproteins and blood levels are lowered. glands. Each gland is composed of an
as they enter the follicles. Parafollicular cells in the thyroid are inner medulla surrounded by a much
■ Formation and secretion of active larger than follicular epithelial cells (Fig. larger outer cortex. A connective tissue
thyroid hormone molecules. This 14.5). They secrete the peptide hormone capsule surrounds each gland. The
involves: calcitonin directly into capillaries. Calci- cortex and medulla develop from differ-
■ uptake of thyroglobulin from tonin secretion is stimulated by high ent embryological origins but both
follicles by endocytosis levels of calcium in blood and its actions secrete hormones. The cortex is derived
■ fusion of endocytotic vesicles help lower blood calcium. Calcitonin, from embryonic mesoderm and the
with lysosomes along with parathyroid hormone (see medulla from neural crest cells. Steroid
■ digestion of thyroglobulin by below), maintains calcium homeostasis. hormones are produced and secreted by
lysosomes, thus forming active Calcium is essential for many body cortical cells, and vasoactive amines by
thyroid hormones functions, e.g. the conduction of nerve cells in the medulla.
Adrenal cortex
The location of endocrine cells, fenes-
trated capillaries and reticulin connec-
tive tissue in the suprarenal cortex
shows three main regions or zonae.
They are:
Chief cells
■ Zona glomerulosa. This is a narrow

region just beneath the capsule Adipocytes
formed by roughly spherical clusters
of endocrine cells supported by
reticulin fibres (Fig. 14.7). Arterioles
supply blood to capillaries in this
region.
■ Zona fasciculata. This is the largest Oxyphil cells
region and it occupies the mid-
portion of the cortex. It is
characterised by rows of endocrine
cells (Figs. 14.7 and 14.8), supported
by reticulin fibres, lying alongside
straight capillaries extending from
capillaries in the zona glomerulosa.
The endocrine cells in this zone are Fig. 14.6 Parathyroid. The lipid has been extracted from the cytoplasm of the adipocytes during
known as spongiocytes as their processing. High magnification.
cytoplasm appears vacuolated in
routine histological sections (Figs
14.7 and 14.8). The apparently
empty vacuoles contained lipids
in life, e.g. cholesterol, stored as a
precursor for the synthesis of
hormones. The lipids were extracted
during histological processing.
■ Zona reticularis. This is the inner
region of the cortex and it surrounds
the medulla. The endocrine cells in Capsule
this region are relatively small (Fig.
14.8) and generally the nucleus and
cytoplasm are densely stained. These
endocrine cells are distributed
irregularly on a reticulin meshwork Zona glomerulosa
between capillaries which are
continuous with those in the zona
fasciculata.
Three groups of steroid hormone,

known as corticosteroids, are produced
from cholesterol by the endocrine cells
in the adrenal cortex. The hormones are
not stored in the cells but are synthe-
sised when needed. The three groups of
Spongiocyte nuclei
steroid hormone are distinguished by
their functions.
■ Mineralocorticoids. The molecules in Zona fasciculata

this group regulate water and salt
concentration via actions on the
distal convoluted tubules of the
kidney (Chapter 13). The major
mineralocorticoid hormone is
aldosterone and it is produced
mainly by cells in the zona Fig. 14.7 Adrenal gland, zona glomerulosa and zona fasciculata of the cortex. Connective
tissue is stained blue. Special stain. Medium magnification.
glomerulosa.
■ Glucocorticoids. This group of

hormones is mainly produced by
cells in the zona fasciculata. One
of the principal glucocorticoids is
cortisol. Glucocorticoid hormones Zona fasciculata
affect many target cells and are
involved in regulating the
metabolism of carbohydrates, fats
and proteins. They are also able to
suppress immune responses.
■ Sex hormones. These steroids are
produced mainly by cells in the
zona reticularis. Most of the
molecules are male sex hormones of
low activity.
The secretion of hormones by the

adrenal cortex is under the regulatory
control of ACTH from the anterior lobe
of the pituitary gland. In turn, ACTH
Zona reticularis
secretion is controlled by a releasing
hormone (corticotrophin rH) from the
hypothalamus. High levels of cortico-
steroids in blood suppress secretion of
corticotrophin rH and ACTH. In addi-
tion, mineralocorticoid levels are affected
by the intake of various mineral salts.
Medulla
Adrenal medulla
The medulla of the adrenal gland is
surrounded by the zona reticularis of the
cortex. Medullary endocrine cells are
modified postganglionic sympathetic Vein in medulla
neurons; they do not have axons. In Fig. 14.8 Adrenal gland, zona fasciculata, zona reticularis of the cortex and
general, medullary cells are large and in medulla. Connective tissue is stained blue. Special stain. Medium magnification.
clusters or cords (Fig. 14.8) near capillar-
ies and are supported by reticulin fibres.
The medulla receives blood from arteri-
oles and from capillaries extending in
from the zona reticularis. All blood from
the cortex drains into veins in the medulla
(Fig. 14.8). There are two principal hor-
mones synthesised by the endocrine cells
in the medulla, adrenaline and noradren-
aline; both are vasoactive amines. Each
hormone is stored in small quantities in
cytoplasmic granules. Release of hor-
mones is stimulated by preganglionic
nerves acting on the endocrine cells in
the medulla. Under stressful conditions,
much larger amounts of medullary hor- Exocrine cells of pancreas
mones may be released.
Pancreas
The pancreas is a flattish organ in the
abdominal cavity. The bulk of the pan-
creas is formed by exocrine cells and
Islet of Langerhans
their secretions enter the gastrointestinal
tract at the duodenum via the pancreatic
duct (Chapter 12). The pancreas also
contains endocrine cells in small clusters
known as islets of Langerhans (Fig. 14.9).
There are about a million islets scattered
throughout the pancreas. Fig. 14.9 Pancreas, islet of Langerhans. Low magnification.
Islets of Langerhans generally are seen

in histological sections as pale staining
areas in comparison with surrounding
exocrine cells (Figs 14.9 and 14.10). The
endocrine cells lie close to capillaries
(Fig. 14.10) and several types have been
identified. All the hormones produced
are involved in regulating carbohydrate
metabolism and other aspects of the func-
tions of the digestive system. Immunohis-
Endocrine cells in islet of tochemical techniques have shown several
Langerhans cell types in each islet, each type secreting
a different hormone. Most of the cells
secrete insulin and are known as beta
cells. Insulin, a polypeptide, reduces blood
glucose levels. The next most populous
cell type, alpha cells, secretes another
Blood vessels in islet of
polypeptide, glucagon, which elevates
Langerhans
blood glucose levels. Other minority cell
populations are involved in regulating
gastrointestinal tract function.
Exocrine cells of pancreas The factors affecting endocrine secre-
tion by the pancreas are numerous. One
of the major factors affecting insulin
secretion is the level of glucose in blood.
Fig. 14.10 Pancreas, islet of Langerhans. High magnification. In addition, sympathetic nerves inhibit
insulin secretion and, conversely, parasym-
pathetic nerves increase insulin secretion.
Pineal gland
The pineal gland is closely associated
Clinical note with the brain. Despite this proximity,
All endocrine glands may secrete abnormally high, or low, levels and in contrast to the pituitary gland,
of hormones. There are numerous causes. Malignant changes in there are no nerves which directly connect
endocrine cells can result in abnormal levels of hormone production. In the pineal gland and the brain. The pineal
other instances, abnormal levels of a particular pituitary trophic hormone, gland responds to changes in light levels.
e.g. TSH, may be caused by inadequate levels of hormone production by It is concerned with the regulation of
other cells, e.g. inadequate levels of TrH from the hypothalamus. In some circadian rhythm, and is influenced by
cases, an abnormal (auto)antibody may develop which binds to a particular hormones from the gonads. The main
circulating hormone and affects the function of that hormone. Some cell types are pinealocytes and interstitial
autoantibodies affect the thyroid gland and result in hypothyroidism cells. Pinealocytes produce melatonin in
manifest as Hashimoto’s disease. the absence of light. The interstitial cells
may be similar to glial cells.
Summary
The endocrine system
Hypothalamus and hypophysis (pituitary gland)
■ The hypothalamus is the part of the brain connected by a (pituitary) stalk to the hypophysis.
■ The hypophysis has a glandular portion (adenohypophysis) and neural portion (neurohypophysis).
■ Some hypothalamic hormones (peptides) affect the function of the adenohypophysis:
■ neurons in the hypothalamus secrete releasing hormones into capillaries in the hypothalamus which pass (in a portal circulation) along the
stalk and stimulate the release of hormones from cells in the adenohypophysis
■ Other neurons in the hypothalamus produce hormones (peptides) which pass via their axons (along the stalk) to the neurohypophysis.
■ Feedback signals from the levels of hormones in blood affect the secretion of most hypothalamic and hypophyseal hormones.
Adenohypophysis
■ Chromophil and chromophobe cells are present:
■ acidophil cells secrete growth hormone or prolactin (proteins)
■ basophil cells secrete thyroid-stimulating hormone or adrenocorticotrophic hormone or follicle-stimulating hormone and luteinising
hormone (glycoproteins).
■ Chromophobe function is not understood
Neurohypophysis
■ Pituicytes support axons from neurons with cell bodies in the hypothalamus.
■ Hypothalamic hormones antidiuretic hormone (ADH) and oxytocin are stored in the ends of the axons (as Herring bodies):
■ ADH affects kidney tubules and decreases the amount of water excreted
■ oxytocin stimulates lactation and contraction of uterine smooth muscle.
Thyroid
■ A simple epithelium synthesises, secretes and stores thyroglobulin (an iodinated protein) as colloid in spherical follicles.
■ These epithelial cells also endocytose the thyroglobulin, convert it into active thyroid hormones (e.g. thyroxine) and secrete them into blood
vessels:
■ thyroid hormones stimulate metabolism.
■ Parafollicular cells secrete the peptide hormone calcitonin directly into blood when blood calcium levels are high. Calcitonin lowers calcium
levels in blood.
Parathyroid glands
■ Chief cells secrete parathyroid hormone when blood calcium is low, which raises calcium levels via its stimulation of the activity of osteoclasts.
Oxyphil and adipose cells are also present.
Adrenal glands
■ Adrenal cortex synthesises, secretes steroids:
■ zona glomerulosa cells secrete mineralocorticoids which affect salt balance
■ zona fasciculata cells (spongiocytes) secrete glucocorticoids which regulate metabolism and are immunosuppressive
■ zona reticularis cells secrete, male sex hormones of low activity.
■ Adrenal medulla secretes vasoactive amines:
■ cells are modified sympathetic neurons which secrete adrenaline or noradrenaline involved in responses (fright, fight and flight) to stress.
Pancreas
■ Islets of Langerhans cells secrete hormones (peptides) which affect carbohydrate metabolism. Insulin is secreted by beta cells and it reduces
blood glucose levels. Glucagon is secreted by alpha cells and it raises blood glucose levels.
Pineal gland
■ Responds to light, secretes melatonin and helps regulate circadian rhythm.
114
Chapter 15
The male reproductive system
The male reproductive system com- the organ of copulation able to deliver iniferous tubules are lined by several
prises paired testes, associated glands, spermatozoa, in semen, into the vagina layers of epithelial cells forming a ger-
ducts and the penis (Fig. 15.1). The of the female reproductive tract. minal (seminiferous) epithelium (Fig.
testes are the male gonads and are 15.2). There are two types of cell in the
the site of production of spermatozoa germinal epithelium of adults: sperma-
(the male gametes). Each spermatozoon togenic cells, which are in layers, and
Testes
(in humans) has 23 chromosomes con- Sertoli cells, which form a single layer
taining the haploid amount of DNA. Each testis is an organ suspended within and are supportive of the spermatogenic
Additionally, testes produce and secrete a pouch of skin known as the scrotum. cells (see below). The germinal epithe-
a group of steroid hormones, the male The testes thus lie outside the abdomi- lium lies on a basement membrane and
sex hormones (androgens), of which nal cavity and this ensures that spermato- is surrounded by a thin layer of loose
testosterone is the main type. The glands genesis (the formation of spermatozoa) connective tissue. This connective tissue
that are associated with the male repro- occurs at a temperature slightly below supports blood vessels (Fig. 15.2), lymph
ductive system are the paired seminal body temperature, a requirement for capillaries, nerves and Leydig (intersti-
vesicles, the prostate and paired bulbo- successful gamete production. Each tial) cells (Fig. 15.3) which secrete andro-
urethral glands. All these glands con- testis is surrounded by a tough connec- gens (see below). Myoid cells (Fig. 15.4)
tribute fluid secretions which support tive tissue covering known as the tunica are closely adjacent to seminiferous
spermatozoa and form semen. The albuginea. Connective tissue septa from tubules and are capable of contraction,
ducts form the reproductive tract and the tunica albuginea penetrate into the thus helping to move the spermatozoa
transport spermatozoa and secretions substance of each testis and divide it along tubules and away from where
from the testes and glands to the urethra. into lobules. One septum forms a wedge they develop.
The urethra is shared by the reproduc- which penetrates the posterior surface After puberty, spermatogenesis begins
tive and urinary systems and it passes of each testis. as spermatogenic cells undergo meiosis
from the bladder through the prostate and differentiation in a cycle of events
and penis and opens at a meatus at the Seminiferous tubules that result in the production of sperma-
glans penis. The urethra transports Located within the lobules of each testis tozoa, a process which takes about 65
urine from the urinary bladder as it is are coiled seminiferous tubules which days in humans. The stages of sperma-
emptied at micturition. The penis is also are the sites of spermatogenesis. Sem- togenesis take different lengths of time
Ductus deferens
Ureter
Urinary bladder Seminal vesicle

(lumen)
Pubic bone Rectum
Prostate Anal canal
Ductus deferens
Anus
Bulbourethral gland
Epididymis
(contains duct of epididymis)
Glans of penis
Testis
Meatus (with seminiferous tubules)
Fig. 15.1 The component parts of the male reproductive system.
The male reproductive system 115
germinal epithelium undergo

Seminiferous tubule lumen regular cycles of mitosis and
produce new diploid cells, i.e. cells
containing the normal number of
chromosomes (46 in humans,
Germinal epithelium comprising 22 homologous pairs
and two sex chromosomes). Some
of the new cells formed by mitosis
remain in the basal layer as
spermatogonia, others move towards
the lumen and enter meiosis.
■ Meiosis. At the start of this phase the
cells begin to enlarge and are known
Germinal epithelium as primary spermatocytes. They
undergo an S phase when they
replicate the DNA in their
chromosomes prior to cell division
(Chapter 2). They then enter the
prophase of the first division in
meiosis (Fig. 15.6), a process which
lasts about 20 days. During this
time, chromosomes begin to coil
Blood in vessel and condense (and stain densely)
and homologous pairs of
chromosomes move close together
Fig. 15.2 Testis. Seminiferous tubules. One tubule appears circular as it is sectioned across its and exchange lengths of DNA. This
length. Medium magnification. exchange introduces genetic
variation to the gametes produced.
The first meiotic division of
meiosis (also known as the
reduction division) continues into
metaphase. Each pair of homologous
chromosomes in each primary
spermatocyte line up together on
Seminiferous tubule the same part of the equator of the
spindle of the metaphase plate, prior
to cell division. (This contrasts with
mitosis, where each chromosome
attaches to a different part of the
equator of the spindle.) At this stage,
the chromosomes are at their most
condensed and densely stained and
are readily identified in histological
Leydig cells sections (Fig. 15.7). The paired
chromosomes then move away
from each other in anaphase and
Germinal epithelium telophase. The result of this
reduction division is the production
of two secondary spermatocytes each
with only half the original number
of chromosomes (i.e. 23 in humans).
Lumen of seminiferous tubule (This reduction division introduces
Fig. 15.3 Testis. Seminiferous tubules and Leydig (interstitial) cells. High magnification. further genetic variation to the new
cells as maternally and paternally
derived chromosomes in the
to complete and, as a result, not all the Spermatogenic cells homologous pairs are randomly
stages are present in the layers of cells The formation of spermatozoa (sperma- arranged on the spindle, and
in any one region of the germinal epi- togenesis) may be divided into three therefore randomly distributed
thelium. The appearance of seminifer- stages: mitosis, meiosis and spermio- between the two offspring cells.)
ous tubules depends on the stages the genesis. These stages begin at about The second meiotic division,
spermatogenic cells have reached in puberty and continue throughout life. known as the mitotic division of
forming spermatozoa and on the angle meiosis, occurs rapidly as
at which they are sectioned (Figs 15.2 ■ Mitosis. In this stage, stem cells chromosomes in secondary
and 15.5). (spermatogonia) at the base of the spermatocytes line up as individuals
the luminal surface of seminiferous

Heads of spermatozoa tubules (Fig. 15.6).
■ Spermiogenesis. During this stage,
Germinal epithelium spermatids differentiate and each
forms one spermatozoon.
Sertoli cell nucleus
Approximately 200 million
spermatozoa are produced daily by
the testes in humans. During
spermiogenesis the spherical
Sertoli cell nucleus spermatids change in form and shed
cytoplasm as they become highly
differentiated spermatozoa
characterised by a head, middle
Myoid cell nucleus region and tail (Fig. 15.8). As
spermatozoa develop, the head
Sertoli cell nucleus regions remain in the epithelium
but the tail regions extend into the
lumen of the seminiferous tubule
(Fig. 15.5). Eventually, spermatozoa
pass into the lumen and fluid
secreted by Sertoli cells (see below)
Fig. 15.4 Testis. Seminiferous tubules, Sertoli cells and myoid cells. Sertoli cell nuclei are pale aids their transport away from the
staining and nucleoli are present. Myoid cells are identified by their long thin nuclei lying adjacent to
seminiferous tubules.
the base of the germinal epithelium. High magnification.
The head of each spermatozoon
contains the nucleus in which the
DNA in the chromosomes is
condensed and stains densely with
Heads of spermatozoa bases such as haematoxylin (Figs
15.4, 15.5 and 15.6). At one end of
the nucleus of a developing
spermatozoon a head ‘cap’ develops
known as the acrosome (Fig. 15.8).
The contents of the acrosome
include hydrolytic enzymes that take
Heads of spermatozoa
part in the acrosome reaction, which
is the process by which the head of
Tails of spermatozoa a spermatozoon penetrates the cells
and structures surrounding the
Lumen of seminiferous tubule
oocyte prior to fertilisation (Chapter
16). The middle region of a
spermatozoon is mainly occupied by
Germinal epithelium mitochondria which provide energy
for the movement of the tail
(flagellum) (Fig. 15.8). The tail has
the 9 + 2 arrangement of
microtubules characteristic of cilia
Fig. 15.5 Testis. Seminiferous tubules. The lumen of one seminiferous tubule is sectioned along its (Chapter 2), and these provide
length. The similarity of the cells in the layers of the germinal epithelium around the tubule reflect their the motive force which allows
synchronisation in the stages of forming spermatozoa. At this magnification heads of spermatozoa spermatozoa to swim. However,
appear as very small blue dots, adjacent to the lumen, but it is not possible to see their individual tails. spermatozoa become self-propelled
only after they have left the testes
and are fully matured, when they
(as they do in mitosis) on the (spermatogonia), and of most other are then able to undertake
metaphase spindle of this division. cells in the body. unidirectional travel at about
The chromosomes then split (along Separation of cytoplasm during 3 mm/minute.
their length) and separate into two meiosis is incomplete and
new cells, known as spermatids. As spermatids derived from one
this cell division is rapid, few cells in spermatogonium are partially joined Sertoli cells
any one histological section are in together. This is thought to aid Sertoli cells are tall and columnar, and
this phase. Each resulting spermatid synchrony of their progression extend from the base of the germinal
has 23 chromosomes with the through the next stage epithelium to the lumen of the semini-
haploid amount of DNA. This is half (spermiogenesis). Groups of newly ferous tubule (Fig. 15.10). The nucleus
the number of chromosomes and formed, related spermatids appear as of Sertoli cells may appear oval or trian-
half the DNA in the stem cells clusters of small, spherical cells near gular and most display a prominent
Fig. 15.6 Testis. Seminiferous tubules,

primary spermatocytes and
spermatids. Primary spermatocytes in prophase
of the first meiotic (reduction) division are
distinguished by their large size and speckled, Spermatozoa heads
clumped chromatin. High magnification.
Primary spermatocytes (in

prophase)
Spermatids
Germinal epithelium
Fig. 15.7 Testis. Seminiferous tubules,

primary spermatocytes undergoing cell
division. Note the difference in the types of
cell in the epithelium on opposite sides of the Germinal epithelium
lumen; dividing cells are only in one region.
Clusters of cells are in synchrony but at different
stages of forming spermatozoa in different parts
of the tubule. High magnification.
Lumen of seminiferous tubule
Nuclei of primary spermatocytes

(dividing)
Acrosome
nucleolus and palely stained chromatin, two compartments is known as the
Head reflecting their high levels of synthetic blood–testis barrier and it ensures that
Nucleus
activity (Figs 15.4 and 15.9). Developing large molecules, e.g. antibodies or micro-
spermatogenic cells are enfolded in the organisms in blood, do not readily pass
Middle Mitochondria lateral cell membranes of Sertoli cells to developing spermatozoa.
and as a result detail of Sertoli cell struc- Sertoli cells are also important in
ture is difficult to distinguish in routine nourishing developing spermatogenic
histological sections. Adjacent Sertoli cells and they phagocytose cytoplasmic
cells are joined to each other near to the fragments released from spermatozoa
basement membrane by tight junctions as they develop. An important compo-
Tail (Fig. 15.10). This arrangement separates nent in the secretions from Sertoli cells
spermatogonia into a basal compart- is an androgen-binding protein. This
ment of the germinal epithelium binds testosterone and helps to ensure
and the developing spermatogenic cells levels in the seminiferous tubules are
(from primary spermatocytes to sper- higher than in the circulation and at a
Fig. 15.8 The components of a matozoa) into an adluminal compart- level adequate for the development of
spermatozoon. ment. The barrier formed between the spermatozoa. In addition, fluid secreted
Sertoli cell nucleus by Sertoli cells helps to move spermato-

zoa away from the testis as at this stage
the spermatozoa are not able to propel
Sertoli cell nucleus themselves.
Variations in germinal epithelium

Primary spermatocyte nucleus
Various groupings of cells at the same
stages of spermatogenesis occur in dif-
ferent regions of the seminiferous
tubules. For example, in some regions
Nuclei of spermatids with
(Fig. 15.5) the condensed heads of sper-
acrosomal caps
matozoa before they are released into
the lumen are apparent, whereas in
other regions none of the developing
spermatids has condensed chromatin
(Fig. 15.9). These groupings of similar
Nuclei of spermatids with cells developing in synchrony occur as
acrosomal caps lengths (Fig. 15.5) or as patches of the
epithelium (Fig. 15.7) in humans. This
variation ensures that mature sper-
matozoa are continuously produced
and always available for release at
ejaculation.
Fig. 15.9 Testis. Seminiferous tubule with Sertoli cells and spermatids developing Leydig (interstitial) cells
acrosomes. High magnification.
Leydig cells are endocrine cells in the
loose connective tissue around seminif-
erous tubules (Fig. 15.3) and they secrete
mainly testosterone. The Leydig cells
Spermatozoon are stimulated to produce and secrete
Lumen testosterone by luteinising hormone
Spermatid secreted by cells in the anterior pituitary
gland (Chapter 14). Testosterone enters
the circulation and stimulates secondary
Secondary spermatocyte sexual characteristics including skeletal
Sertoli cell muscle development and the pattern
cytoplasm
of hair growth. However, circulating
Primary spermatocyte
levels of testosterone are insufficient to
Nuclei of
Sertoli cells maintain spermatogenesis. Testosterone
levels in the testis are kept high enough
to stimulate spermatogenesis as the
Tight junction
androgen-binding protein secreted by
Spermatogonium
(in basal compartment) Sertoli cells binds testosterone in the
Basement membrane testis. Another hormone from anterior
pituitary cells, follicle-stimulating
Myoid cells
hormone, stimulates Sertoli cells to
Fig. 15.10 Sertoli cells in a seminiferous tubule. The relationship of adjacent Sertoli cells is shown secrete the androgen-binding protein.
forming a basal compartment containing spermatogonia and an adluminal compartment containing
developing spermatozoa closely associated with the Sertoli cells.
Ducts draining seminiferous
tubules
Most seminiferous tubules are coiled
Clinical note loops which have straight regions (tubuli
Infertility There are numerous causes of infertility. Low recti) at each end through which fluid
numbers of spermatozoa in an ejaculate is one reason why and spermatozoa leave. The tubuli recti
infertility occurs. Malnutrition and alcoholism are factors which also affect drain into a meshwork of spaces, lined
fertility. by cubodial epithelium, known as the
Immotile cilia syndrome is a state which affects all the ciliated cells in the rete testis. The rete is embedded in the
body as well as the flagellum of each spermatozoon. The inability of wedge of connective tissue which
spermatozoa to move and reach an oocyte in the uterine tube will affect extends into each testis from the tunica
fertility. A person with immotile cilia is also likely to suffer from frequent albuginea. The contents of the rete testis
respiratory tract infections as inhaled microorganisms are not swept along drain into 12 to 15 ductuli efferentes,
the mucus escalator and away from the lungs. which in turn drain into a single duct in
the epididymis.
Ducts draining each Stereocilia

testis (Fig. 15.1)
Ductus epididymis
Each ductus epididymis is a highly con- Smooth muscle cells
voluted tubule surrounded by a thin
layer of smooth muscle cells. Each is
tightly packed in an epididymis by con-
Basal cell nucleus
nective tissue and attached to the poste-
rior surface of a testis. At the superior Columnar epithelial cell
pole of each testis is the head of the cytoplasm
epididymis where ductuli efferentes
Stereocilium
drain fluid and spermatozoa from each
testis into the duct of the epididymis.
From the lower pole of each testis (the
Spermatozoa in lumen
tail of the epididymis) the duct of the
epididymis continues as the ductus (vas)
deferens (see below).
The epithelium lining the ductus Fig. 15.11 Ductus epididymis. High magnification.
epididymis is pseudostratified and com-
posed of basal and columnar epithelial
(principal) cells (Fig. 15.11). The basal
cells are stem cells from which the
columnar cells are derived. Large cyto- Lumen of ductus deferens
plasmic processes, known as stereocilia,
extend from the surface of the columnar Connective tissue
cells. Stereocilia do not have the struc-
ture or function of cilia; instead, they
Smooth muscle layer
function as microvilli and resorb fluid (longitudinal)
and remnants of cytoplasm from devel-
oping spermatozoa. This fluid resorp-
tion and contraction of smooth muscle
Smooth muscle layer
around the ductus epididymis (Fig.
(circular)
15.11) facilitate the movement of sper-
matozoa away from the testis and
towards the ductus deferens.
Smooth muscle layer

Ductus deferens (longitudinal)
Each ductus deferens is a thick muscu-
lar tube that conducts fluid and sperma-
tozoa at ejaculation from a ductus
epididymis into an ejaculatory duct in
the prostate. At the ejaculatory duct,
secretions from a seminal vesicle and Blood vessel lumen
the prostate gland are added to the ejac-
ulate and the combined contents Fig. 15.12 Ductus deferens. Very low magnification.
(seminal fluid) enter the urethra, where
it passes through the prostate.
Each ductus deferens is lined by a zones) (Fig. 15.14). The largest zone is
Glands of the male
pseudostratified columnar epithelium the outer zone, and the inner is the
reproductive system
similar to that of the epididymis. smallest. The secretions drain either
There are three thick layers of smooth Prostate directly or via short or longer ducts into
muscle surrounding the ductus defer- The prostate is a glandular structure the urethra.
ens arranged as inner and outer longi- that lies beneath the urinary bladder The prostatic epithelium is stimulated
tudinal layers and a middle circular and surrounds part of the urethra. It to secrete by testosterone. It varies in
layer (Fig. 15.12). Contraction of this is a compound tubuloalveolar gland appearance between being a pseudo-
relatively large amount of smooth (Chapter 3) whose epithelium is sup- stratified columnar epithelium (Fig.
muscle is initiated and coordinated ported by a fibroelastic stroma which 15.13) when stimulated and a low,
by sympathetic nerves and it ensures contains numerous irregularly arranged simple cuboidal epithelium when testo-
that strong contractions propel the smooth muscle cells (Fig. 15.13). The sterone levels are low. The lumina of
seminal fluid along the ductus deferens whole organ is surrounded by a connec- prostatic glands store the secretions
and on through the urethra at tive tissue capsule. The gland is described which are emptied into the urethra at
ejaculation. in three zones (outer, middle and inner ejaculation. The propulsive force that
Capsule
Outer zone
Middle zone
Inner zone
Urethral lumen
Ejaculatory duct
Stroma
Connective tissue
Glands
Epithelium
Fig. 15.14 A transverse section through the
prostate and urethra.
Smooth muscle cell cytoplasm
Each tube within a seminal vesicle is

lined by a highly folded epithelium
Corpus amylacea
which may appear as a pseudostratified
columnar epithelium or simple, low
cuboidal epithelium. The appearance
and function of the epithelium is affected
Epithelium by the amount of circulating male sex
hormones. The epithelial-lined tube in
Fig. 15.13 Prostate gland. The muscle cells within the stroma stain more intensely pink than the each seminal vesicle is supported by
connective tissue cells and fibres. Low magnification. fibroelastic connective tissue. Smooth
muscle, arranged as an inner circular
and outer longitudinal layer, surrounds
moves the secretions at ejaculation is tatic glands (Fig. 15.13) but they are of
the coiled tube and on the exterior of
due to contraction of smooth muscle unknown significance.
the seminal vesicles there is a layer of
cells (Fig. 15.13) in the prostatic stroma
loose fibroelastic tissue.
(under the control of sympathetic Seminal vesicles
Contraction of the smooth muscle in
nerves). Prostatic secretions contain Paired seminal vesicles are located on
seminal vesicles, stimulated by sympa-
citric acid, which may provide an energy the posterior surface of the urinary
thetic nerves, propels their secretions
source for spermatozoa, and various bladder. Each contains a highly coiled
into the ejaculate. The secretions from
proteins including a form of acid phos- tube which drains into an ejaculatory
the seminal vesicles are watery and
phatase unique to the prostate. With duct where, at ejaculation, it is added to
contain fructose, which acts as an
age, concretions (corpora amylacea) fluid from a ductus deferens. (Seminal
essential energy source for spermatozoa.
composed of calcified glycoproteins vesicles in humans do not store
They also contain a lipochrome pigment
may be present in the lumina of pros- spermatozoa.)
which imparts a yellowish colour to
semen.
Bulbourethral glands
Clinical notes The bulbourethral glands are paired
Benign prostatic hypertrophy This condition afflicts 30–40%
glands that lie at the base of the
of men over the age of 50 years, and more than 95% of men over
penis and drain directly into the urethra.
the age of 80 years. As it is the inner zone of the gland that is affected, any
They secrete a small volume of mucoid
enlargement can readily put pressure on the urethra and affect the ability to
material that precedes the ejaculation of
pass urine.
semen and acts as a lubricant along
Prostate cancer Cancer of the prostate affects about 30% of males over
the urethra; it may also assist with
the age of 75 years, and in older men it is almost always present. However,
lubrication of the vagina during sexual
in older men it is usually a very slow growing form of cancer and the
intercourse.
individuals usually die from some other disease. In cancer of the prostate, it
is usually the outer zone that is affected and, in its most aggressive form, it
may spread via the bloodstream before any swelling compresses the urethra
Urethra
and inhibits micturition.
A diagnostic test used to indicate an increased risk of prostatic cancer is a In males, the urethra shares urinary and
blood test to measure the levels of circulating prostate-specific antigen (PSA). reproductive functions and is longer
This glycoprotein is secreted by prostatic epithelial cells into the lumina of than the urethra in females, in whom
the glands and normally does not circulate in blood. If prostatic epithelial its sole function is to drain urine from
cells have spread beyond their basement membrane their secretions may the bladder. The urethra in males is
circulate in blood. However, PSA may also be raised in patients with benign described as having three regions: the
prostatic hypertrophy, so its usefulness as a diagnostic test is limited. prostatic, membranous and penile
(spongy) urethra. The initial portion,
draining the urinary bladder, is the pro-

static urethra. It is lined by transitional Lumen
epithelium and is surrounded by the
prostate. At ejaculation, the prostatic
urethra drains secretions from the pros- Epithelium
tate and the ejaculatory ducts (carrying
secretions from seminal vesicles, sper-
matozoa and fluid from the testes). The
membranous part of the urethra is short
and connects the prostatic urethra to the
penile urethra. It is lined by stratified or
pseudostratified columnar epithelium.
The penile urethra is the longest region
of the urethra. It is also lined by strati-
fied or pseudostratified columnar epi-
thelium (Fig. 15.15) and in places it has
deep folds (Fig. 15.16). Near the meatus
at the end of the penis the urethral
epithelium changes and becomes a
stratified non-keratinising squamous
epithelium. The lamina propria sup-
porting the epithelium in all regions of
the urethra is composed of loose fibroe- Lumen of vein
lastic connective tissue.
Penis
The penis consists of three cylinders
(corpora) of erectile tissue, each sur-
rounded by a dense fibrous connective
tissue sheath (the tunica albuginea)
and enclosed by thin skin. One cylinder,
the corpus spongiosum, surrounds the
penile urethra (Fig. 15.15), and the other Lumen of artery
two (corpora cavernosa) lie dorsally.
The erectile tissue of the corpora con-
sists mainly of interconnecting venous
Fig. 15.15 Penile urethra, corpus spongiosum. Connective tissue is stained red. Special stain.
spaces (Fig. 15.17) which are virtually Medium magnification.
empty when the penis is in its flaccid
state.
The penis has a rich blood supply that
flows in helicine arteries (Figs 15.15 and
15.17), which are spiral in form in the
flaccid state. Most blood, in the flaccid
state, flows directly via arteriovenous
shunts linking arterioles (supplied by the Lumen
helicine arteries) directly to deep venules
and veins draining the penis. However, Epithelium
some arterial blood perfuses capillaries
and thus supplies the penis with oxygen
and nutrients. During an erection, the Connective tissue
arteriovenous shunts are closed and arte-
rial blood is diverted and fills and swells
the venous spaces (Fig. 15.17) in all the
corpora. As a result, venous return from
the penis is restricted, the penis increases
in volume, it lengthens, and the helicine
arteries extend. The arrangement of the
connective tissue around the corpora
Infolds from lumen
(Figs 15.15 and 15.17) ensures that the
penis extends as a column. Parasympa-
thetic nerves supplying smooth muscle
around arterioles in the penis act as
vasodilators and are responsible for the Fig. 15.16 Penile urethra. Very low magnification.
haemodynamic changes producing an

erect penis.
Ejaculation is under the control of
sympathetic nerves. They stimulate
contraction of smooth muscle cells in
the ductus deferens (and other ducts),
in the prostate gland and in seminal
Venous spaces vesicles. The pressure exerted on the
urethra by the engorged corpus spongi-
osum is less than that in the corpora
cavernosa. It is normally sufficient to
prevent micturition, but not the power-
Lumen of artery
ful propulsion of semen at ejaculation.
After ejaculation, sympathetic stimula-
tion ceases and smooth muscle contrac-
Venous spaces tion ceases. Parasympathetic stimulation
also ceases and this opens the arteriov-
enous shunts and the flaccid state of the
penis is restored.
Fig. 15.17 Penile urethra, corpus cavernosus. Connective tissue is stained red. Special stain.
Summary
The male reproductive system
■ This consists of paired testes, ducts, associated glands and the penis.
Testes
■ Testes contain coiled seminiferous tubules lined by a stratified germinal epithelium (which produces spermatozoa), Sertoli cells (which
support the developing spermatozoa) and Leydig (interstitial) cells (between the tubules) which produce testosterone under the influence of
luteinising hormone from the anterior pituitary.
Spermatogenesis
■ This is the series of stages involved in producing spermatozoa: it begins at puberty and continues for life.
■ Spermatogenesis involves mitosis of stem cells (spermatogonia), meiotic division of spermatocytes and spermiogenesis:
■ some cells produced by mitosis of spermatogonia enter meiosis and become primary spermatocytes; others remain as stem cells
■ primary spermatocytes replicate the DNA of their chromosomes prior to meiotic division
■ in the first division (reduction) of meiosis, a primary spermatocyte divides into two secondary spermatocytes, each with half the original
number of chromosomes
■ in the second division (mitotic) of meiosis, each secondary spermatocyte divides into two spermatids, each with half the amount of DNA
(and half the original number of chromosomes)
■ spermatids differentiate into spermatozoa (the process of spermiogenesis):
■ spermatozoa each have a head, neck and tail (the tail beats and provides unidirectional propulsion).
Ducts
■ Ducts drain spermatozoa and fluid secreted by Sertoli cells from seminiferous tubules.
■ Immotile spermatozoa pass from each testis into a ductus epididymis as fluid is absorbed by epithelial cells lining these ducts.
■ At ejaculation, spermatozoa pass rapidly from each ductus epididymis into and along a ductus deferens, propelled by the peristaltic
contraction of the thick muscle layers surrounding each ductus deferens.
Associated glands
■ These add secretions to the ejaculate which provide nutrients for spermatozoa:
■ the prostate gland has smooth muscle in the stroma which contracts and expels the secretions from the epithelial cells
■ the paired seminal vesicles each contain a coiled tubule lined with epithelial cells and surrounded by smooth muscle.
Penis
■ The penis comprises three corpora of erectile tissue, each surrounded by a dense fibrous connective tissue sheath and enclosed by thin skin.
One cylinder, the corpus spongiosus, surrounds the penile urethra.
■ increased blood flow into the blood vessels in erectile tissue, particularly in the paired corpora cavernosus, produces an erect penis.
■ At ejaculation, fluid from Sertoli cells, spermatozoa and secretions from the prostate and seminal vesicles enter the prostatic region of the
urethra, pass along the penile urethra and are discharged at the meatus of the urethra.
123
Chapter 16
The female reproductive system
In humans the female reproductive Blood (and lymphatic) vessels and human females, between puberty and
system consists of paired ovaries and nerves pass to each ovary within this the menopause, ovarian follicles vary
the reproductive tract comprising paired membrane. The ovary is divided into widely in appearance and size as they
uterine tubes, a uterus and a vagina two main regions, an outer cortex and are in various stages of development.
(Fig. 16.1). Prior to puberty, as in males, inner medulla, though the demarcation Some stromal cells are irregularly dis-
the reproductive system in females is between the two is not well defined. A tributed in whorls in the cortex and
quiescent. At puberty, hormones from simple cuboidal epithelium, known as others lie around developing follicles
the pituitary gland initiate developmen- the germinal epithelium, covers the as layers known as theca (Fig. 16.2).
tal changes which are prerequisites for cortex of each ovary and is continuous Some of the fibroblast-like cells differen-
reproduction. In contrast to the male with the peritoneal epithelium. This tiate and are able to secrete steroid
reproductive system, the female system name arises from the erroneous suppo- hormones.
after puberty in humans is regulated by sition that ‘germ’ cells capable of becom-
hormones secreted by the anterior pitui- ing ova (the female gametes) developed
Oogenesis and ovarian
tary gland on a monthly, cyclical basis. from this layer. It is now known that
follicle development
The cycle of activity begins at puberty the ‘germ’ cells which are the stem cells
and is manifested by the onset of men- (oogonia) for female gametes develop in In utero and prepubertal stages
struation (the loss of blood, cells and the embryonic yolk sac and migrate to In a developing female embryo from
secretions from the uterus which drain the ovaries during fetal development in about the sixth week in utero, primor-
through the vagina). The time when utero (see Mitchell B, Sharma R. Embry- dial, diploid oogonia migrate from the
menstruation begins is known as the ology: An Illustrated Colour Text. Else- yolk sac and enter the developing ovary.
menarche and it occurs between 9 and vier: 2004). From this time oogonia undergo mitosis
15 years of age. During each monthly and produce more oogonia. By about
menstrual cycle female oocytes differen- Cortex of the ovary the fifth month of fetal life each ovary
tiate and usually a single, mature oocyte Immediately below the germinal epithe- contains 5–7 million oogonia and migra-
is shed from an ovary each month, a lium is a thin layer of dense irregular tion of oogonia from the yolk sac stops.
process described as ovulation. The connective tissue, the tunica albuginea. In contrast to spermatogonia, which
ability to produce a haploid gamete (an A connective tissue stroma containing continue to act as stem cells for sper-
ovum), ovulate, conceive, support one or some fibroblast-like cells supports struc- matozoa production throughout life in
more developing fetuses and give birth tures in the cortex known as ovarian males, mitosis of oogonia stops before
continues from puberty until the meno- follicles (Fig. 16.2). Ovarian follicles birth and no new oogonia are formed
pause. During the menopause, which comprise an oogonium, or a developing thereafter. Indeed, the majority of
may begin between 45 and 50 years of oocyte, surrounded by epithelial cells. In oogonia die before birth.
age, the menstrual cycles and ovulation
become irregular and then cease.
During and beyond the menopause the
Perimetrium (broad ligament)
hormonal signals required to stimulate investing uterus and uterine tubes Fundus of uterus
the cyclical activity of the ovaries and
Wall of Lumen of
the uterus also cease but the factor(s) uterine tube
uterine tube
that cause this cessation are not
understood. Fimbriae of
uterine tube
Ovaries Lumen of uterus Ovary

The ovaries are located in the pelvic Internal os
Body of uterus
cavity and are small (approximately 3 × Cervix
2 × 1.5 cm) and roughly ovoid in shape.
Ectocervix
Each ovary is attached by a stalk of Vaginal wall
double-layered membrane to the pos- External os
Lumen of vagina
terior surface of each side of the broad
ligament (the peritoneal membrane
surrounding the uterus) (Fig. 16.1). Fig. 16.1 The components of the female (human) reproductive system.
chromosomes derived originally from

Tunica albuginea the mother and the father. Primary
oocytes remain in the first prophase of
Primary oocyte (nucleus in
prophase) in primordial follicle
meiosis unless they become atretic and
die in the ovary or, after puberty, are
shed at ovulation.
Scar tissue
At birth there are 1–2 million primary
oocytes remaining and each is sur-
rounded by a layer of flattened epithelial
cells known as follicular cells. Each
Thecal layers primary oocyte and the surrounding fol-
licular cells form a spherical, primordial
follicle. Such follicles are predominant
Follicle (primary) in the outer regions of the cortex
(Fig. 16.2). Many primordial follicles die
during childhood, leaving only about
Zona pellucida 400 000 at puberty.
Cytoplasm of developing primary

Ovarian follicles in menstrual cycles
oocyte (nucleus not in section)
During each menstrual cycle several
primordial follicles begin to develop but
Granulosa cell layers of follicle many become atretic (see below) and
the oocyte dies. Usually, only one oocyte
is released from a developed follicle
every 28 days at ovulation, so that the
lifetime total of female gametes shed is
Basement membrane of follicle only around 400. In adults, ovarian
Fig. 16.2 Ovary. A primary follicle and several small, primordial follicles are present in the follicles may be defined by the stage of
cortex surrounded by connective tissue cells and fibres. Connective tissue is stained red. Special their development and are categorised
stain. Medium magnification.
into four types: primordial, primary, sec-
ondary (antral) and Graafian (mature)
follicles.
■ Primordial follicles (Figs 16.2 and

16.3). These consist of a primary
Primary oocyte (nucleus) in oocyte, in the prophase of the first
unilaminar primary follicle meiotic division, surrounded by a
single layer of flattened epithelial
cells which is surrounded by a
basement membrane.
■ Primary follicles. Each month, several
primordial follicles begin to develop
and form primary follicles. This
Primary oocyte (nucleus) in development is stimulated by
primordial follicle follicle-stimulating hormone from
the anterior pituitary gland. In each
developing primary follicle the
primary oocyte increases in volume
Zona pellucida and the surrounding flattened
follicle cells become cuboidal or
Primary oocyte cytoplasm columnar in shape and are then
Granulosa cell nucleus known as granulosa cells. At this
stage, the follicles are described
as unilaminar primary follicles
(Fig. 16.3), and they are deeper
in the ovary than primordial
Fig. 16.3 Ovary. Two primary and several primordial follicles. The nucleus of the primary oocyte follicles.
in one primary follicle and the nuclei in the primordial follicles have the clumped chromatin typical of Unilaminar follicles become
cells in prophase of the first meiotic division. Special stain. High magnification. multilaminar follicles as mitotic
activity is high in granulosa cells and
All surviving oogonia become primary meiosis. This is the phase in which the new cells form layers around
oocytes before birth as they replicate homologous chromosomes pair and each developing primary oocyte (Figs
their DNA and then enter the prophase exchange short regions of DNA, thus 16.2–16.4). During this time, the
of the first (reduction) division of introducing genetic variation to the primary oocyte enlarges considerably
The female reproductive system 125
hormone from the anterior pituitary

Connective tissue of tunica gland binds to cells of the theca
albuginea interna and this stimulates them to
produce steroids. These steroids are
converted by granulosa cells into
oestrogens (female steroid
hormones). Oestrogens are
involved in stimulating the uterus
each month (see below) and in
Zona pellucida the development and maintenance
of the secondary sexual
characteristics and of the mammary
glands.
■ Secondary follicles. Some
multilaminar primary follicles
Primary oocyte nucleus develop and enlarge further, under
the influence of follicle-stimulating
Primary oocyte cytoplasm
hormone. The granulosa cells
produce fluid, liquor folliculi, which
appears in spaces between the
Granulosa cell layers of
granulosa cells (Fig. 16.5). These
multilaminar follicle
follicles are described as secondary
(antral) follicles. Gradually, the fluid-
filled spaces coalesce into a single
large space, the antrum, and
Fig. 16.4 Ovary. Multilaminar follicle. Connective tissue is stained red. Special stain. High development proceeds with the
magnification. formation of a Graafian (mature)
follicle.
■ Graafian (mature) follicles. As the
single antrum enlarges the granulosa
cells appear as layers around the
fluid and the layers become thinner
as the follicle enlarges further. The
oocyte, surrounded by granulosa
Thecal layers
cells, bulges into the fluid in the
antrum and the whole bulge is
known as the cumulus oophorus
Granulosa cell layers
(Fig. 16.6).
Primary oocyte nucleus Graafian follicles may become very
large (2.5 cm in diameter) and bulge
from the surface of the ovary prior
to ovulation. The primary oocyte
(which was arrested in utero in
Liquor folliculi prophase of the first reduction
meiotic division) completes the first
meiotic division just prior to
ovulation. The result is one large
secondary oocyte with half the
original number of chromosomes
Fig. 16.5 Ovary. Secondary (antral) follicle. Special stain. Low magnification. (23 in humans) and a small cell,
known as the first polar body (also
with 23 chromosomes), which
and a prominent deposit of separates the (epithelial) granulosa degenerates.
condensed material known as the cells from surrounding connective
zona pellucida appears between the tissue (Fig. 16.2) becomes more
oocyte and the granulosa cells (Figs apparent. Atresia of follicles
16.2–16.4). Primary oocytes, which Stromal cells around each primary Most developing follicles fail to become
may grow to 120 μm in diameter, follicle form two layers during this mature Graafian follicles. Atresia may
may appear to lack a nucleus (Figs phase: the theca interna and theca occur at any stage of follicle develop-
16.2 and 16.3) in routine histological externa. The inner theca is well ment and it involves the death of granu-
sections which, at only 5–10 μm vascularised whereas the outer theca losa cells (Fig. 16.7) and the oocyte.
thick, can fail to include the nucleus. is composed of fibrous connective Atretic follicles are gradually replaced by
As primary follicles grow the tissue, although the layers are not scar tissue containing fibroblasts and
basement membrane which always distinct (Fig. 16.2). Luteinising collagen (Fig. 16.2).
Clinical note
Ovarian cysts These
are common. They are
Granulosa cell layers fluid-filled structures which
develop from ovarian follicles or
corpora lutea. Some may be
Granulosa cells of cumulus follicles which have failed to
oophorus rupture at ovulation. They may
cause pain and/or bleeding. In the
Zona pellucida condition known as polycystic
ovary syndrome a range of
Primary oocyte cytoplasm changes may be present, e.g.
menstruation may be irregular or
cease and the patient may become
obese and infertile. Cysts,
occasionally, become malignant.
The factors causing cysts to form
are not understood.
Fig. 16.6 Ovary, Graafian follicle. Special stain. Low magnification.
begin to secrete female steroid hor-

mones, mainly progesterone. The secre-
tory cells pack the corpus luteum (Fig.
16.8), which may grow into a sphere up
to about 2 cm in diameter by day 25 of
the menstrual cycle. The progesterone
Granulosa cell layers with secreted by the corpus luteum is essen-
nuclear fragments
tial in preparing the uterus for the pos-
sible arrival of a fertilised ovum and the
establishment of pregnancy.
If pregnancy is established the corpus
luteum doubles in size and is an essen-
Nuclear fragments
tial source of progesterone during the
first months of pregnancy in humans.
If fertilisation and implantation do not
occur, the corpus luteum degenerates,
a scar forms from fibroblasts and
collagen fibres, and the resultant struc-
ture, known as a corpus albicans, per-
sists in the ovary for some time.
Fig. 16.7 Ovary. Atretic follicle. Densely stained fragments of DNA and disruption of the layers of
granulosa cells characterise atretic follicles. This follicle is large and had developed into a secondary
follicle. The developing primary oocyte is not in the plane of section but it too will be undergoing Medulla of the ovary
degeneration. Connective tissue is stained red. Special stain. Low magnification. The medulla is the central core of the
ovary and it is surrounded by the cortex
except where vessels and nerves are con-
Ovulation burst from the antrum of the follicle and nected to the ovary. Stromal cells, similar
Ovulation usually happens once at the enter the peritoneal cavity. Further to those in the cortex, are present in the
mid-point (day 14) of every menstrual development of the oocyte normally medulla but follicles are not present.
cycle. It is the process whereby a second- occurs only if it passes from the perito-
ary oocyte and the surrounding cluster neal cavity into the lumen of the uterine
tube (see below).
Uterine tube and fertilisation
of granulosa cells (the corona radiata)
are expelled from a Graafian follicle and Uterine tubes
away from the surface of the ovary. Ovu- Formation of a corpus luteum Each uterine tube in humans is about
lation is brought about as the increasing After ovulation, under the influence of 10 cm long. The lumen at one end of
volume of the Graafian follicle puts luteinising hormone from the anterior each tube is open to the peritoneal
pressure onto the tunica albuginea and pituitary gland, a corpus luteum devel- cavity. This end is formed by frilly,
surface epithelium of the ovary and also ops. It forms from the remnants of finger-like projections (fimbriae) of the
compresses blood vessels in the region. granulosa cells from the ruptured Graa- tube. Fimbriae are important in helping
This is coincidental with a breakdown fian follicle, and cells and blood vessels guide the oocyte (released at ovulation
of the wall of the follicle in the same which grow into these remnants from into the peritoneal cavity) into the lumen
region. The oocyte, granulosa cells the theca interna. The theca and granu- of the uterine tube. The other end of the
forming the corona radiata and fluid losa cells forming the corpus luteum uterine tube opens into the uterus (Fig.
uterus also help to prevent the

passage of microorganisms into and
along the uterine tubes and into the
peritoneal cavity.
Corpus luteal cell nucleus
■ The middle layer is a muscularis.
There are two, thin, ill-defined layers
of smooth muscle cells, an inner
circular and an outer longitudinal
Corpus luteal cell cytoplasm layer. Peristaltic contractions of the
smooth muscle cells assist in moving
the contents of the lumen.
■ The outer layer is a thin covering of
serosa. This layer is continuous with
the broad ligament covering the
uterus.
Fertilisation
Once a secondary oocyte, surrounded
by cells of the cumulus oophorus, enters
the uterine tube it remains there for 2–3
days, during which time it is capable of
being fertilised by a spermatozoon. At
Fig. 16.8 Ovary. Corpus luteum. Connective tissue is stained red. Special stain. Medium this stage, it has started the second
magnification. (mitotic) division of meiosis but is sus-
pended in metaphase pending possible
fertilisation by a spermatozoon.
Fertilisation occurs in the uterine tube
when a spermatozoon passes between
Connective tissue lamina propria cells of the cumulus oophorus and
penetrates the cytoplasmic membrane
of the oocyte. Once fertilised, the oocyte
completes meiosis and this restores the
diploid number of chromosomes. (A
second polar body is released at this
division and degenerates.) The fertilised
oocyte undergoes rapid rounds of cell
division (mitosis) and develops into a
Cilia of columnar epithelial cells blastocyst. Further details of the subse-
quent development of the blastocyst are
described elsewhere (see Mitchell B,
Sharma R. Embryology: An Illustrated
Colour Text. Elsevier: 2004).
After fertilisation, the blastocyst
passes to the uterus, carried there in the
fluid flowing from the uterine tube. The
timing of the arrival of the blastocyst in
Columnar epithelial cell nucleus the uterus is critical. The blastocyst has
to be sufficiently developed so that it is
able to attach to the uterine epithelium.
In addition, it must arrive in the uterus
Fig. 16.9 Uterine tube. High magnification.
when, and not before, the uterus is in a
receptive state. This state is dependent
16.1). The structure of each uterine tube provides an environment in the on progesterone from the corpus luteum
consists of three layers: lumen of the tube in which the (see below).
(secondary) oocyte and spermatozoa
■ The inner layer is a mucosa. The can survive and fertilisation can
Uterus
mucosa is highly folded and consists occur. The ciliated cells beat and
of simple columnar epithelial cells assist in wafting the oocyte toward The uterus in humans is a single mid-
on a basement membrane and a the uterus. The fluid flow towards line organ. It is able to accommodate
thin, supporting connective tissue the uterus must not be stronger and facilitate the development of the
lamina propria (Fig. 16.9). Some than the ability of spermatozoa to blastocyst and differentiation of the
epithelial cells have cilia and others swim from the uterus and along the embryo and its further growth as a fetus.
do not. The non-ciliated cells are tube. The fluid in the uterine tube In addition, the uterus supports the
secretory and the fluid they produce and its direction of flow towards the development of the placenta and expels
the fetus and placenta at parturition. glands dip deep into the connective endometrium is a relatively narrow
The uterus is divided into three regions tissue of the lamina propria and region, though highly significant,
(Fig. 16.1). The superior part is the extend to the myometrium (Fig. since it is this layer that undergoes
fundus. The body is the largest part of 16.10). Some of the epithelial cells cellular proliferation and replaces
the uterus, into which the uterine tubes are secretory and others have cilia. the superficial layer shed at
open. The most inferior part of the The superficial layer of the menstruation.
uterus is the cervix, which projects and endometrium is shed at ■ Myometrium. This is the muscularis
opens into the vagina. menstruation or, if pregnancy of the uterus. It is composed of three
The wall of the uterus in the fundus occurs, adapts and functions as a or four thick and ill-defined layers of
and body regions is composed of three support for the blastocyst and the smooth muscle. Arcuate arteries in
layers: endometrium, myometrium and developing placenta and embryo the middle of the myometrium
perimetrium. (and its development into a fetus). supply the helical arteries in the
Within the superficial layer there are endometrium. Hypertrophy and
■ Endometrium. This is a mucosa; it helical arteries. These supply the hyperplasia of smooth muscle cells
forms the inner layer and varies in endometrium as it increases in are stimulated by oestrogen and
structure under the influence of thickness in response to the these changes are particularly
oestrogens and progesterone (see hormonal changes occurring during important in pregnancy.
below). The endometrium has an the menstrual cycle (and in Contractions of the myometrium are
inner basal layer and a superficial pregnancy). It is from the capillaries stimulated by oxytocin from the
(functional) layer. A simple, supplied by these vessels that blood posterior pituitary (Chapter 14) and
columnar epithelium lines the is lost during menstruation. The by prostaglandins from the region of
uterine lumen and branched tubular inner basal layer of the the uterus in pregnancy known as
decidua (see Mitchell B, Sharma R.
Embryology: An Illustrated Colour
Text. Elsevier: 2004). These
Myometrium
contractions result in expulsion of
the fetus and placenta at parturition.
■ Perimetrium (Fig. 16.1). The thin,
outer, serosal (peritoneal) covering
Connective tissue in basal layer of of the uterus is known as the
endometrium perimetrium. It consists of a single
layer of squamous epithelial cells
Uterine glands (sectioned transversely) beneath which is loose connective
tissue attached to the myometrium.
The perimetrium invests most of the
uterus as the broad ligament,
encloses vessels and nerves passing
to the uterus and is continuous with
the peritoneum. As the uterus
expands during pregnancy the fluid
secreted onto the surface of the
Connective tissue in functional layer of perimetrium by its epithelial cells
endometrium ensures relatively friction-free
movement between the uterus and
adjacent structures such as gut tubes.
Uterine glands (sectioned longitudinally) Cervix of the uterus

The cervix is the lower part of the uterus,
and the lower part of the cervix projects
into the vagina as the ectocervix (Fig.
Fig. 16.10 Uterus. Body region, proliferative phase. Very low magnification. 16.1). In the cervix, the smooth muscle
forming the myometrial layer in the rest
of the uterus is mostly replaced by con-
nective tissue containing collagen and
Clinical note elastin fibres. The lumen of the cervix
Ectopic pregnancy Sometimes a developing blastocyst becomes communicates with the lumen of the
arrested in its passage from the uterine tube to the uterus. It may body of the uterus at the internal os and
then develop and attach to the mucosal epithelium of the uterine tube. The opens into the vagina at the external os.
wall of the uterine tube is not able to sustain the developing blastocyst for The lumen of the cervix is lined by a
long and blood vessels in the wall of the tube rupture. The result is simple columnar epithelium. Deep slits
haemorrhage, possibly into the peritoneal cavity and possibly into the uterus and tubes, lined by columnar epithelial
and showing as a vaginal discharge. These events usually cause severe pain cells, extend into the connective tissue
and loss of the embryo and can cause death of the woman. of the cervical wall. Cervical epithelial
cells are palely stained in routine (H&E)
histological preparations (Fig. 16.11) in

contrast to the rest of the uterus. Cervi-
cal epithelial cells synthesise and secrete
mucus, which is rich in carbohydrates.
This mucus does not stain strongly in
routine preparations. Cervical mucus Connective tissue
varies in viscosity during the menstrual
cycle. The mucus is relatively watery at
mid-cycle when ovulation occurs, but
more viscous at other times and during
pregnancy. The thicker mucus helps
prevent the entry of microorganisms Lumen of cervical mucous glands
into the uterus. The watery mucus pro-
vides relatively little resistance to swim-
ming spermatozoa during the short
Cytoplasm of columnar epithelial
time after ovulation that an oocyte is
cells
available for fertilisation in the uterine
tube. Cervical mucus drains to the vagina Lumen of cervix of uterus
and acts as a lubricant during sexual
intercourse. The surface of the cervix Fig. 16.11 Cervix of uterus. Medium magnification.
where it projects into the vagina is
covered by stratified, squamous, non- Lumen
keratinising epithelium, similar to
that which lines the vagina itself (see
below). Blood
Lumen of degenerating uterine

The menstrual cycle gland
The menstrual cycle occurring in human

females mainly affects the reproductive
Blood
system, particularly the ovaries and the
uterus. The cycle lasts for an average of
28 days and is described as having three
phases: menstrual, proliferative (follicu-
lar) and secretory (luteal).
■ Menstrual phase. Conventionally, the

menstrual cycle is said to begin as
Lumina of ‘saw-toothed’ uterine
blood is lost from the vagina at the
glands
start of menstruation. The phase
lasts until vaginal bleeding stops
(after about 4 days). Menstruation
occurs, if fertilisation has not Connective tissue in functional
occurred, as a result of a rapid fall in layer of endometrium
the levels of progesterone (and
oestrogen) secreted by cells in the
corpus luteum in the last 2 or 3
days of the cycle. At the start of the
menstrual phase the endometrium is
thick and the glands are distended
and have a characteristic shape (Fig.
16.12). The superficial (functional)
layer is shed during this phase and
bleeding occurs from damaged
vessels in the endometrium. At the
end of this phase only the basal
layer remains intact.
Connective tissue in basal
■ Proliferative (follicular) phase. After layer of endometrium
menstruation, the damaged
endometrium is repaired as
epithelial, stromal and endothelial
cells in the basal layer proliferate Fig. 16.12 Uterus. Body region, at the start of menstruation. The appearance of the glands is
and replace the shed functional layer typical of the secretory stage. The distribution of blood shows that menstruation has started. Very low
with straight tubular glands and magnification.
connective tissue stroma (Fig. 16.10).

This phase lasts from about day 5 Clinical notes
of the cycle to about day 14. The Fibroids These are benign tumours which develop from the
proliferative and repair activities are smooth muscle cells of the myometrium of the uterus. As these
regulated indirectly by follicle- tumours enlarge they disrupt the normal repair of the endometrium, and
stimulating hormone (FSH) from the heavy bleeding may occur. In many women, after the menopause with the
anterior pituitary gland. FSH associated fall in steroid secretions from the ovaries, fibroids shrink and do
stimulates the growth of ovarian not need to be excised.
follicles and as the number of Cervical carcinoma Most cervical cancers develop from the stratified
granulosa cells increases they secrete squamous epithelium in the region of the ectocervix. A papillomavirus
increasing levels of oestrogen into causes many cervical carcinomata. Routine screening of smears of cells
the blood. The timing of the sampled from the ectocervix may detect early changes in the appearance of
secretion of these oestrogens and the the epithelial cells which could become cancerous. Further histological
effect they have on endometrial examination of a biopsy sample from the region may provide information
repair is important because it helps on whether the basement membrane has been disrupted and epithelial cells
to ensure that the uterus is in a have become malignant and spread.
receptive state appropriate for the
arrival of a blastocyst.
■ Secretory (luteal) phase. This phase
Lumen of vagina
begins after ovulation (on day 14)
and lasts until menstruation (i.e.
from day 15 to day 28). After
Superficial ‘empty’ epithelial
ovulation, luteinising hormone (LH) cells
from the anterior pituitary
stimulates the formation of the
corpus luteum, which secretes
progesterone. In this phase, under
the influence of progesterone, the
whole endometrium becomes
thicker and oedematous and the
glands deepen and become saw-
toothed in shape (Fig. 16.12). The
epithelial cells accumulate glycogen
Epithelial cells in basal layers
and secrete glycoproteins into the
lumen, activities which could provide
nourishment for a developing
blastocyst. The timing of these
events is also essential in preparing Connective tissue
the endometrium for the blastocyst,
particularly as the uterine secretions
will nourish the developing embryo
prior to the formation of the
placenta.
The vagina Fig. 16.13 Vagina. Low magnification.
The vagina is a fibromuscular tube that

leads from the uterus to the exterior. cells arising from stem cells in the basal mucus and a watery transudate from
The wall of the vagina consists of three layer. Glycogen, released from shed the vaginal wall facilitate the entry of the
layers: an inner mucosa, a fibromuscular cells, is metabolised by non-pathogenic penis during sexual intercourse.
layer and an outer connective tissue cov- bacteria in the vaginal lumen and lactic
ering which attaches the vagina to adja- acid is released. This symbiosis is impor-
cent structures, e.g. the urethra. tant as the lactic acid maintains a low
Mammary glands
The vaginal mucosa, in humans, pH in the vaginal lumen and this pro- Mammary glands are paired structures
comprises a non-keratinising, stratified, vides a hostile environment for many lying on the anterior chest wall. After
squamous epithelium and a connective types of pathogenic bacteria which could puberty in human females the glands
tissue lamina propria. Cells in the upper gain access to the upper parts of the develop under the influence of oestro-
layers of the vaginal epithelium are char- tract (and the peritoneal cavity). The gen and progesterone (mainly from the
acterised by their content of glycogen, wall of the vagina mostly comprises ovaries). During pregnancy and lacta-
which is extracted during routine histo- fibrous connective tissue, which includes tion oestrogen, progesterone and prolac-
logical processing and so the cells appear mainly collagen and elastin fibres. Some tin (from the anterior pituitary gland)
empty (Fig. 16.13). The surface epithelial smooth muscle cells are also present. further stimulate the glands. In females,
cells are gradually shed and replaced by During sexual stimulation, cervical mammary glands secrete milk, the
defining substance for nourishing the

offspring of mammals. Mammary
glands are also present in males, though
considerably less well developed. It is
important to recognise their presence Duct in lobule
in males since, like their counterparts
in females, they too may develop Connective tissue within lobule
cancer.
Connective tissue around lobule
Mammary glands are classified as
compound tubuloalveolar glands
(Chapter 3). Each gland contains about Adipose cells
20 lobes separated by connective tissue,
and each lobe drains through a lactifer-
ous duct to a nipple. Connective tissue
Fig. 16.14 Breast in non-pregnant, non-lactating female. Medium magnification.
comprising collagen, fibroblasts and
adipose cells separates each lobe and
supports the tubuloalveolar glands
within the lobes. The number of adipose
cells present varies from individual to
individual.
Mammary glands in non-pregnant
women are in a resting state. Within
each lobe there are lobules comprising
clusters of epithelial-lined ducts (Fig.
16.14) separated by loose connective
Lumen of duct draining
tissue, but there are no secretory cells. lobules
During pregnancy, under the influence
of hormones (oestrogen, progesterone
and prolactin) the epithelial cells of
the ducts proliferate, the duct system
extends, and spherical clusters of secre-
tory cells form as alveoli at the ends of Connective tissue between
lobules
the ducts. Ducts and alveoli swell and fill
the lobules. The secretory alveoli are
lined by cuboidal epithelial cells and are Lumina of alveoli in a lobule
surrounded by myoepithelial cells. The (distended)
epithelial cells synthesise and secrete
milk, which is released from the nipple
post partum. During lactation, alveoli
may appear distended with secretion
Fig. 16.15 Breast in lactating female. Alveoli in lobules are distended with secretion and are
(Fig. 16.15). The expulsion of milk is
apparent at this low magnification. It is possible to identify only a large duct in interlobular connective
stimulated by suckling. It involves the tissue but not ducts in the lobules. Low magnification.
secretion of oxytocin (from the poste-
rior pituitary) and the contraction of
myoepithelial cells surrounding the
alveolar epithelium.
Milk contains proteins, lipids, lactose
(milk sugar), minerals and vitamins,
which together constitute the nutrition
required by infants. Milk also contains Clinical note
antibodies and various immune cells. Breast cancer The most common swellings and disorders
At this early stage, the infant has little occurring in breasts are not cancerous. However, the epithelial
immunity of its own and the passage cells lining the ducts in the breast may become cancerous in women (and
of antibodies in milk from the mother men) and produce lumps or distortions. Spread of cancerous cells from the
is the principal means by which a breast occurs via the rich network of blood and lymphatic vessels in the
newborn is afforded some immune pro- breast. Early diagnosis of the cell types present in breast lumps and
tection from potential microbiological appropriate treatment improves survival rates.
invaders from their new world.
Summary
The female reproductive system
■ This consists of paired ovaries and the reproductive tract (paired uterine tubes, a single uterus (in humans) and a vagina).
Ovaries
■ Ovaries contain ovarian follicles, which contain oocytes.
■ Each month, after puberty, several follicles begin to grow:
■ follicle cells increase in number and are known as granulosa cells; they surround a developing oocyte and secrete mainly oestrogens.
■ Usually, only one follicle grows to maturity each month and one oocyte is shed at ovulation (other developing follicles become atretic and
die).
■ After ovulation, a corpus luteum develops from the remnants of the follicle and a surrounding layer (theca) of connective tissue cells and
blood vessels.
■ The pituitary hormones follicle-stimulating hormone and luteinising hormone, respectively, control the development of follicles and corpora
lutea.
■ If fertilisation does not occur the corpus luteum degenerates, progesterone levels fall and menstruation occurs.
■ If fertilisation occurs, the corpus luteum grows and secretes progesterone, which prepares the uterus to support the developing embryo until
the placenta forms.
Uterine tubes
■ These are lined by a simple epithelium composed of secretory and ciliated cells.
■ They have sparse connective tissue lamina propria connecting the epithelium to a muscularis of two layers of smooth muscle.
■ They are covered by a serosal (peritoneal) membrane.
■ They receive the oocyte after ovulation, are the site of fertilisation and transfer the blastocyst to the uterus.
Uterus
■ A simple epithelium lines most of the uterus and glands dip into the mucosa as far as the muscularis externa:
■ most of the mucosa is shed at menstruation and bleeding occurs
■ after menstruation, the remaining cells in the basal mucosal layer proliferate (under the influence of oestrogens) and repair the superficial
layer
■ after ovulation (under the influence of progesterone) the mucosa thickens, the epithelial cells begin to store glycogen and secrete
glycoproteins. The glands become saw-toothed in shape.
■ The muscularis externae is formed of several layers of smooth muscle which undergoes hyperplasia and hypertrophy during pregnancy.
■ Part of the uterus, the cervix, is lined by columnar epithelial cells which secrete mucus. The outer wall of the cervix is formed mostly of
connective tissue.
Vagina
■ A stratified squamous epithelium lines the vagina and the upper cells contain glycogen.
■ The vaginal wall is formed largely by connective tissue.
133
Glossary
Acinus a spherical unit of secretory cells in an exocrine Circadian cyclical activity occurring over a 24 hour period.
gland.
Diploid the number of chromosomes in somatic cells of a
Adenoma an abnormal growth of glandular epithelial cells species comprising pairs of homologous chromosomes and
that is non-cancerous. a pair of sex chromosomes. This is twice the number
present in the germ cells (ova and spermatozoa). (There are
Adluminal refers to structures adjacent to the lumen of a
22 pairs of homologous chromosomes and a pair of sex
tube.
chromosomes in humans.)
Allergen a substance capable of provoking an immune
Effete worn out or dying.
(allergic) reaction in an individual involving the production
of specific immunoglobulins. Extracellular outside the cell.
Alveolus a small cavity, e.g. the blind-ended epithelial sacs Fusiform a long structure narrowing at each end like a
at the ends of airways in the lungs. spindle.
Anaphylaxis an excessive (sometimes fatal) specific reaction Gamete a mature male or female germ cell which contains
to allergens that results from breakdown of mast cell the haploid number of chromosomes. A male gamete
granules and leads to sudden hypotension and severe (spermatozoon) fertilises a female gamete (oocyte), and
bronchoconstriction. forms a zygote (with the diploid number of chromosomes)
which develops into a new individual.
Anastomosis a union or joining together of parts, e.g. of
arteries, often forming a network. Genitalia external reproductive structures of each sex.
Antibody a protein (immunoglobulin) produced as part of Germ cells primitive, undifferentiated reproductive cells
an immune response to a specific molecule (antigen) and (oogonia in females and spermatozoa in males).
able to bind specifically with that molecule. Haemorrhage escape of blood from vessels.
Antigen a molecule (protein or carbohydrate) capable of Haploid the set of chromosomes found in germ cells (i.e.
stimulating the production of an antibody. the 23 chromosomes in human germ cells).
Apoptosis programmed cell death (programmed in the DNA). Hilum a depressed region on the surface of some organs,
Benign non-cancerous (harmless). e.g. the kidney, where structures enter or leave the
organ.
Blastocyst the stage reached when the solid mass of cells
which have developed from a fertilised egg form a hollow Histochemistry the application of chemical reactions to
structure comprising two distinct components. One sections of tissues to demonstrate certain chemical
component will form the placenta and the other an embryo. components.
Bronchoscopy a technique in which a flexible telescope is Histopathologist a specialist in diagnosing abnormalities

introduced into a patient’s trachea to inspect the interior of by examining tissue sections using a microscope.
the bronchi. Homeostasis the physiological changes which occur and
Cancer a general term applied to any malignant growth ensure relatively constant conditions are maintained within
(tumour) with potentially unlimited growth and spread; it the body of living organisms.
is usually fatal if untreated. Homologous similar.
Cancerous refers to cancer. Humoral blood borne.
Carcinoma a malignant tumour formed by an abnormal Hypertonic indicates a fluid with a higher concentration of
growth of epithelial cells that penetrate their basement solutes than in blood plasma.
membrane and spread to other sites.
Hypotonic indicates a fluid with a lower concentration of
Cell the basic unit of living organisms. solutes than in blood plasma.
Chromosome a linear structure in the nucleus that contains Immunohistochemistry the application of labelled
hereditary material (DNA and associated proteins) in the antibodies to demonstrate specific antigens in tissue
form of genes. sections.
Cilium a projection from the apical (opposite to the basal) Inflammation (inflammatory reaction) dilation of blood
surface of a cell containing a core of microtubules capable capillaries, increased vascular permeability and infiltration
of moving the cilium. In the respiratory tract, coordinated of immune cells, including neutrophils, macrophages,
beating of many cilia on individual cells moves particles out lymphocytes and plasma cells to the site. Redness, swelling,
of the tract. tenderness and pain may occur.
134 GLOSSARY
Interstitium region lying between cells, often occupied by Papilla a projection from a surface of a tissue or organ.
tissue fluid. It may have a specific normal purpose or be abnormal.
Intracellular within a cell. Paracrine indicates a type of secretion exerting local effects,
e.g. as carried out by some neuroendocrine cells.
Isotonic indicates a fluid with the same concentration of
solutes as blood plasma. Parenchyma the main cell type in an organ associated with
its principal function.
In vitro literally in glass. Not in living individuals, e.g. in
tissue culture systems. Parietal related to the wall of a cavity.
Lumen hollow centre of a tubular structure or organ, e.g. Pelvic cavity the lower part of the trunk containing pelvic
urinary bladder. organs.
Malignant harmful or cancerous, applied to the Peritoneum the serous membrane investing the walls of
uncontrolled proliferation and growth of cancer cells. the abdominopelvic cavity and covering the organs
contained therein.
Matrix extracellular matrix is the material outside cells,
and intracellular matrix the components of the cytoplasm Pheromone a naturally occurring molecule from an
within cells supporting the organelles and cytoskeleton. individual that evokes a behavioural response via the
olfactory system of an individual of the same species.
Meatus an opening to the outside of the body.
Photomicrograph a photograph taken using a microscope
Mesenchyme primitive embryonic connective tissue. and camera.
Mesentery the double-layered serosal (peritoneal) Prostaglandins a class of molecule derived from fatty acids
membrane attaching many regions of the gut to the that are widely produced in the body and act locally on a
posterior abdominal wall and supporting vessels passing to variety of cells, e.g. they affect the contraction of the smooth
and from the gut. muscle in the uterus in pregnancy and affect blood flow in
Metastasis the process whereby malignant, cancerous cells many regions.
spread to distant sites from their original site (i.e. the Serous membrane membrane that lines the walls of, and
primary tumour). Also a mass of cancerous cells growing at covers organs in, the three cavities of the trunk, i.e. the
a (secondary) site distant from their original site. pericardial, pleural and abdominal cavities.
Microorganism life forms visible only with a microscope, Somatic of the body. Describes all the cells of the body
e.g. bacteria and viruses. except the male and female germ cells. The somatic
nervous system is that part of the system under
Mucous membrane an epithelium (and its supporting
conscious control.
connective tissue) that covers inner surfaces of the body
(a mucosa). Most mucous membranes secrete mucus which Stroma the connective tissue supporting parenchyma.
keeps the surface moist.
Synovial one of the three different types of joint,
Mucus a secretion of complexes of large carbohydrate characterised by a synovial membrane lining the capsule of
molecules and proteins which are viscous (slimy). the joint (and by articulating surfaces covered by hyaline
cartilage).
Neoplasm a new growth which may originate from
any of the primary tissues and may be benign or System (of the body) a group of organs and structures
malignant. carrying out specific, related functions.
Neuroendocrine indicates cells derived from the neural Tissue the material from which the body is made: there
crest in the embryo, dispersed in the body which secrete are four primary tissue types (epithelial, connective, muscle
hormones. Some secretions have both local and systemic and nerve).
effects; some act as neurotransmitters.
Tract anatomically connected and functionally related
Oedema swelling in tissues caused by excessive structures, e.g. gastrointestinal tract. Also refers to a bundle
accumulation of tissue fluid. of nerve cell cytoplasmic processes passing through the
brain or spinal cord.
Organ a collection of primary tissues joined in a specific
location and carrying out specific functions. Tumour a mass of cells (usually abnormal) which
proliferate and grow abnormally.
Organelle a specific structure in cell cytoplasm with a
particular function. Vasoactive amine an amine that influences the calibre of
blood vessels.
Organism a fundamental life form capable of independent
existence. Visceral of an organ (especially in the thorax or abdomen).
135
Index
Figures and tables are comprehensively referred to from the text. Therefore, significant material in figures and tables have only been given a page
reference in the absence of their concomitant mention in the text referring to that figure. Entries in bold indicate references to the glossary.
A asthma, 80, 82 see also specific types of vessels bronchus, 79

astrocyte, 38 bone, 59, 60–8 larynx, 78
acidophil, 107 atretic ovarian follicle, 125 cell type, 60, 61–3 trachea, 78
acrosome, 116 atrium, 69, 71 formation, 63–7 cells, 5–12
ACTH (adrenocorticotrophic autoimmune disorder (and growth see growth blood see blood
hormone), 108, 111 autoantibody), 55 mineral density loss, 68 bone, 60, 61–2
actin, 7, 9 endocrine gland, 112 remodelling, 67 brain see brain
muscle, 7, 26 autonomic nervous system, 33 bone marrow, 53–4 cartilage, 59–60
skeletal muscle, 27, 28 efferent neuron, 36 fetal development, 65 connective tissue, 21, 25
adenohypophysis, 106, 107, 107–8 ganglion, 37–8 Bowman’s capsule, 99, 101 division, 10–12
adipose cell (adipocyte), 3–4, 21 see also parasympathetic nervous brain, 39 spermatogenic cells, 115–16
adipose tissue, 22, 24 system; sympathetic nervous barrier between blood and, 38, 40 immune see immune system
adrenal gland, 24, 109–11 system cells, 38 muscle see muscle
adrenaline, 111 axo-dendritic synapse, 36 astrocyte, 38 organelle, 5, 7–9, 134
adrenocorticotrophic hormone axon, 33, 34, 36, 37 microglia, 38, 53 skin, 44–5, 53
(ACTH), 108, 111 peripheral nerve, 39 neuron, 33–36 small intestine, 88
afferent neuron see sensory neuron oligodendrocyte, 38 stomach, 87
agranulocyte, 51–2 B breast (mammary gland), 17, 45 see also specific cell types
air–blood barrier, 81 lactating, 3, 131 cell cycle, 10–12
aldosterone, 102 B lymphocyte, 51, 52 bronchiole, 77, 79–80 spermatogenic cell, 115
alimentary canal, 83–96 lymph node, 56 terminal, 80–1 central nervous system (CNS), 33,
alveolus, 133 basement membrane bronchopulmonary segment, 79 34
lung, 81 collagen, 22 bronchus, 79 see also brain; spinal cord
mammary gland, 131 glomerular, 99 bronchus-associated lymphoid centrosome, 7, 10
anaemia, 50 abnormal thickening, 104 tissue (BALT, non- cervix, 128–9
anal canal, 91 testis, 23 encapsulated), 79 chemotherapy, 92
anaphase, 10–11 basophil (adenohypophyseal cell), brown adipose tissue, 24 chief cells
spermatogenic cell, 115 107–8 Brunner’s gland, 90 parathyroid, 109
anaphylaxis, 133 basophil (blood cell), 51 bulbourethral gland, 120 stomach, 87
angina, 71 bile canaliculus, 92 chloride ion, renal handling, 102
angiotensin, 103 bile duct, 92 C chondroblast, 59
antibody, 52, 133 cuboidal epithelium, 14 chondrocyte, 59–60, 64, 65, 66
see also autoimmune disorder bipolar neuron, 33–4, 35 C (parafollicular) cell, 108–9, 109 chromatid, 10, 11
antidiuretic hormone (ADH), 102–3, bladder, gall, 92 calcification of cartilage matrix, 66 chromatin, 6, 10
108 bladder, urinary, 104 calcitonin, 62, 109 chromosome, 6, 133
antigen-presenting cell, 53 cancer, 105 calcium hydroxyapatite, 60 in meiosis, 12
aorta, 72 transitional epithelium, 15–17, cancellous bone, 62–3, 63 oogenesis, 124
apocrine gland, 17 104 cancer see malignant tumours spermatogenesis, 115, 116
sweat gland, 17, 45 blastocyst, 127, 130, 133 capillary in mitosis, 10, 11
apositional growth blood, 49, 49–52 blood, 69, 71–2, 74–5 chyle, 87
bone, 61–2 barrier between air and, 81 renal/glomerular, 98, 99 cilium, 9
cartilage, 60, 65 barrier between brain and, 38, 40 skeletal muscle, 27 respiratory tract, 15, 77, 78–9, 79
appendicitis, 92 barrier between testis and, 117 lymphatic, 75 uterine tube, 127
appendix, 92 cells, 21, 49–53 carbohydrate, cytoplasmic, 9 see also immotile cilia syndrome
areolar connective tissue, 22–3 synthesis in marrow, 53 carcinogen, bladder, 105 circulatory system, 69–76
artefact, 3–4 blood vessel (vasculature; blood carcinoma, 20, 133 see also blood vessel; heart
artery, 69, 71, 73–4 supply), 69, 71–5 cervix, 130 circumvallate papilla, 85
elastin, 22, 72, 73 adenohypophysis connections, skin, 48 cirrhosis, 95
renal supply, 98 107 see also malignant tumours Clara cell, 80
smooth muscle 73 kidney, 97–8 cardiovascular system, 69–76 CNS (central nervous system),
wall, 72 penis, 121 see also blood vessels; heart nucleus, 37
arteriole, 71, 73–4 skin, 47 cartilage, 59, 59–60 collagen, 22
renal, 98, 99 squamous epithelium bone formation and growth, 64– cartilage, 50, 59
arthritis, 68 (= endothelium), 14, 19 5, 66 muscle/tendon, 27, 61
136 INDEX
collecting duct, 102–3 cardiac muscle, 30 compound/stratified see stratified gametes, 133
colon, 91 detrusor muscle, 104 epithelium formation, 12
columnar epithelium diaphysis, 64–5, 65, 66, 67 gland see glands see also ovum; spermatozoon
simple, 14–15 digestive system, 83–96 kidney ganglion, 37–8
small intestine, 88 distributing artery, 73 collecting duct, 102 gap junction, 10
stratified, 15 DNA, 6 distal convoluted tubule, 102 smooth muscle, 30
respiratory system, 15, 77–8 cell cycle and cell division, 10, loop of Henle, 102 cardiac muscle, 30
compact bone, 62, 63 11 proximal convoluted tubule, 101 gastrointestinal tract, 86–92
conducting artery, 73 ductus deferens, 119, 122 lining and covering structures, gastro-oesophageal junction, 86
connective tissue, 13, 21–5 ductus epididymis, 119 13–17 genetic disorders
alveolus (lung), 81 duodenum, 86, 87, 90–1, 95 membrane, 17–18 anaemia, 50
bone, 61 ovary, 123 bone growth, 68
cell type, 21, 25 E prostate, 119 genital tract see reproductive system
extracellular matrix, 22 recognising, 18–19 germinal epithelium
heart, 70, 71 ectopic pregnancy, 128 repair, 20 ovary, 123
liver, 92 efferent neuron, 35–6 respiratory, 15, 77–8, 80, 81 testis, 114, 115, 116, 117, 118
lymph node, 56 egg see ovum simple, 13, 13–15 glands (epithelial), 17–18
mammary gland, 131 ejaculation, 118, 119, 120, 121, 122 bronchiole, 80 digestive system, 83–95
muscle, 26–30 elastic cartilage, 59, 60 see also endothelium, loop of endocrine system, 106–113
nerve, 39 elastin, 22, 60 Henle female reproductive system,
recognising, 18–19 alveolus, 81 testis, 23, 114–118 128–131
spleen, 54–5 artery, 22, 72, 73 tongue, 85 male reproductive system, 114,
type, 22–4 bronchiole, 79 urinary tract, 15–17, 103, 104 119–20
ureter, 103 electron microscopy see kidney see subheading above methods of secretion, 17, 18
continuous capillary, 74 ultrastructure vagina, 16, 130 respiratoy system, 77–80
contraction, muscle, 7, 26, 31, 36 endocardium, 70, 70–1 erection, penile, 121–2 skin, 45–6
cardiac, 30, 70, 71 endochondral ossification, 64–6 erythrocyte see red blood cell unicellular, 17
skeletal, 27, 36 endocrine gland, 17, 24, 106–13 erythropoietin, 103 see also specific named glands
smooth, 30, 36 pancreas as, 92, 110 exocrine glands, 17 glial cell, 38
bronchiole, 80 reticulin in, 23 pancreas, 92, 111 glomerulus, 99
detrusor, 104 endocytosis, 7, 8 skin, 45–6 disease, 105
large intestine, 91 proximal convoluted tubule exocytosis, 7, 8 filtration, 99–101
oesophagus, 85 (kidney), 101 expiration, 77 glucagon, 112
prostate, 120 endometrium, 128 extracellular matrix, 10, 134 glucocorticoid, 111
villus, 90 menstrual cycle, 129, 130 connective tissue, 22, 25 glycogen, cytoplasmic, 9
convoluted tubule endomysium, 27 glycoprotein, cytoplasmic, 9
distal, 101, 102 endoneurium, 39 F goblet cell
proximal, 101 endoplasmic reticulum, 7–8 large intestine, 91
corpus cavernosum, 121, 122 rough see rough endoplasmic Fallopian tube, see uterine tube respiratory tract, 77–8, 78, 80
corpus luteum, 126, 129, 130 reticulum fat and fat cell see adipose cell; small intestine, 88
corpus spongiosum, 121, 122 smooth see smooth endoplasmic adipose tissue Golgi apparatus, 8–9
cortex reticulum female reproductive system, 123–32 gonadotrophins, 108
adrenal, 109, 110 endothelium, 14, 19, 72 fenestrated capillary, 74 see also follicle-stimulating
kidney, 97 artery, 72 fertilisation, 127 hormone; luteinising
lymph node, 56 capillary, 74 male infertility, 118 hormone
ovary, 123 endothelium-lined sinuses of fetus, oocyte/ovarian development, Graafian follicle, 125, 126
corticosteroid, 110, 111 lymph nodes, 56 123 granulocyte, 51
crypt of Lieberkühn, 90 vein, 72 fibroblast, 21, 22, 60 granulosa cell, 124, 125, 130
cuboidal epithelium enzymes fibrocartilage, 59, 60 grey matter
kidney gastrointestinal, 86, 87 fibroid, 129 brain, 39
ascending limb of loop of pancreatic, 95 filiform papilla, 85 spinal cord, 37, 39
Henle, 101, 102 eosin, 2 filtration, renal, 99–101 ground substance, 22
collecting duct, 102 eosinophil, 51 fixation, 1 growth
descending limb of loop of epicardium, 70, 71 flagellum, 9 bone, 61–2, 63–7
Henle, 101, 102 epidermis, 15, 18, 42–5, 47 spermatatozoon, 116 cessation, 67
simple, 14 epididymis, 119 in immotile cilia syndrome, 118 cartilage, 60, 65
stratified, 15 epiglottis, 78 follicle, ovarian, 123, 123–5, 130 growth hormone, 107
cyst, ovarian, 126 epimysium, 27 atresia, 125 growth plate, epiphyseal (EGP), 65,
cystic fibrosis, 82 epinephrine (adrenaline), 111 follicle-stimulating hormone (FSH), 66
cytoplasm, 6–9 epineurium, 39 108 gut-associated lymphoid tissue
molecules stored in, 9 epiphyseal growth plate (EGP), 65, female, 124, 125, 130 (GALT), 84, 91
cytoskeleton, 7 66 male, 118
epiphysis, 64–5 follicular phase of menstrual cycle, H
D growth, 67 129–30
epithelium, 13–20 formaldehyde, 1 haematopoiesis, 53–4
deep vein thrombosis, 76 abnormal growth and fungiform papilla, 85 haematoxylin, 2
dendrite, 33, 37 proliferation, 20 hair follicle, 46
peripheral nerve, 39 alimentary canal mucosa, 83 G Hassal’s corpuscle, 54
see also axo-dendritic synapse mouth, 84 Haversian system (incl. canal), 62,
dendritic cell, 53 oesophagus, 86 G0 phase of cell cycle, 10, 12 63
dense connective tissue, 22, 23 large intestine, 91 G1 phase of cell cycle, 10, 11–12 heart, 69–70
dermis, 45, 47 small intestine, 88–90 G2 phase of cell cycle, 10 muscle, 26, 28–30, 31
desmosome, 10 stomach, 87 gall bladder, 92 contraction, 30, 70, 71
Index 137
hypertrophy and hyperplasia, ion, renal handling, 101, 102 pharyngeal wall (tonsil), 57, 85 monocyte, 52
31 islet of Langerhans, 111–12 lysosome, 9 motor end plate, 37
see also myocardium motor neuron, 36
hemidesmosome, 10 J M mouth, 84
hepatic artery, 92 mucosa (mucous membrane), 19,
hepatic portal vein, 92 jejunum, 87 macrophage, 21, 52, 53 134
hepatocyte, 19, 92 joint lung alveolus, 81 alimentary canal, 83
heterochromatin, 6 cartilage, 59 non-migratory (Kupffer), liver, large intestine, 91
histochemistry, 2, 133 inflammatory disorder, 68 92 small intestine, 90
histology, interpretation in, 3–4 synovial, 59, 134 macula adherens, 10 stomach, 87
holocrine secretion, 17 juxtaglomerular apparatus, macula densa, 103 bladder, 104
hormones, 106 103 male female reproductive tract
adrenal, 110–11 mammary gland, 131 endometrium, 128
hypophyseal, see below pituitary K reproductive system, 114–22 uterine tube, 127
hypothalamic, 107, 108 malignant tumours, 20, 133, 134 vagina, 130
pancreatic, 112 keratin, 7, 15, 42 bladder, 105 respiratory, 77
pituitary keratinised stratified squamous breast, 132 ureter, 103
anterior, 107–8 epithelium, 15 cervix, 130 see also epithelia
posterior, 108 keratinocyte, 42, 44, 45 chemotherapy, 92 mucosa-associated lymphoid tissue
thyroid, 109 kidney, 97–103 endocrine, 112 (MALT), 57
see also female and male Kupffer cell, 92 metastasis, 20, 58, 134 mucous gland/cell
reproductive systems prostate, 120 salivary gland, 84, 85
hyaline cartilage, 59, 59–60 L skin, 48 tongue, 85
in bone formation and growth, white blood cell, 52 trachea, 78
64–5 lactating breast, 3, 131 mammary gland, 130, 131 mucous membrane see mucosa
bronchus, 79 lamina propria, 19 mammotrophin (prolactin), 107, mucous neck cell, 87
larynx, 78 bladder, 104 130, 131 mucus, 134
trachea, 78 intestine, 88–91 Marfan syndrome, 22 cervix, 129
hydroxyapatite, 60 Langerhans cell, 44, 53 mast cell, 21, 52 intestine,
hyperplasia, muscle, 31 Langerhans islet, 111–12 matrix see extracellular matrix large, 91
hypertrophy large intestine, 91–2 median eminence, 108 small, 88
chondrocyte (epiphyseal plate), larynx, 78 medulla stomach, 86, 87
66 leucocyte see white blood cell adrenal, 109, 111 multiple sclerosis, 40
muscle, 31 leukaemias, 52 lymph node, 56 muscle, 13, 26–32
prostate, benign, 120 Leydig cell, 114, 115, 118 ovary, 126 cell (muscle fibre), 26, 26–30
hypothalamus, 106–7 Lieberkühn’s crypt, 90 renal, 97 synapse between axon and,
releasing hormones, 107, 108 light microscopy, staining for, 2 megakaryocyte, 53 37
lipid, cytoplasmic, 9 meiosis, 12 connective tissue, 26–30
I liver, 92–5 oogenesis, 124 contraction see contraction
cirrhosis, 95 spermatogenesis, 115 hypertrophy and hyperplasia,
ileum, 87, 91 hepatocyte, 19, 92 Meissner’s corpuscle, 47 31
immotile cilia syndrome, 118 red blood cell, 50 melanocyte, 44–5 nerve supply to, 31, 37
immune system, 53–7 reticulin fibre, 22, 23, 92 melanoma, malignant, 48 in skin, 47
cell, 51–3 long bone, growth and remodelling, membrane type, 26
lung, 81 67 cell, 6 see also specific types
non-specific response, 53 loop of Henle, 101, 101–2 epithelial, 18 muscularis externa in alimentary
small intestine, 91 loose connective tissue, 22–3 serous, 18 canal, 83–4
specific response, 53 lung, 77, 79 mucous, see mucosa large intestine, 91
see also autoimmune disorders immune cell, 81 menopause, 123 oesophagus, 85
immunohistochemistry, 2, 133 luteinising hormone (LH), 108, menstrual cycle, 123, 124–6, stomach, 86
infantile respiratory distress 130 129–30 muscularis mucosae (muscle layer
syndrome, 82 lymph, 55, 75 Merkel cell, 44, 47 of the mucosa), 19
infertility (male), 118 lymph node, 55–6, 75 merocrine gland, 17 alimentary canal, 83
inflammation, 133 plasma cell, 52, 56 sweat gland, 45–6 large intestine, 91
infundibulum, hypothalamic, tumour spreading to, 58 mesangial cell, 103 small intestine, 90
108 lymph vessel, 55, 56, 75 mesentery, 134 myasthenia gravis, 55
inspiration, 77 lymphocyte, 51–2 metaphase, 10 myelin, 34
insulin, 112 appendix, 93 spermatogenic cell, 115, 116 myoblast, 27
intercalated disc, 30 bronchus, 79 metastasis, 20, 58, 134 myocardium, 70
intercellular junction, 9–10 lymph node, 56 microglia, 38, 53 infarction, 71
intermediate filament, 7 nasopharynx, 78 microscopy see also heart, muscle
interphase, 10 production, 54 electron see ultrastructure myoepithelial cell, 18, 26
interstitial cell (Leydig cell), 114, small intestine, 88 light, staining for, 2 salivary gland, 84
115, 118 spleen, 55 microtubule, 7, 10 sweat gland, 45
interstitial growth, cartilage, 60, thymus, 54 cilium and flagellum, 9 myofibril, 27
65 see also specific types spermatazoon, 116 myofibroblast, 26
intervertebral disc, 60 lymphoid follicle, 56, 57 microvillus, 9 myofilament, 26, 27
intestinal gland, 90 lymphoid tissue (non-encapsulated), small intestine, 90 myoglobin, 27, 28
intestine, 87–92 57 milk, breast, 131 myoid cell, seminiferous tubule,
large, 91–2 appendix, 92 mineralocorticoid, 110 114
small see small intestine bronchus-associated (BALT), mitochondrion, 7 myometrium, 128
intramembranous ossification, 64 79 mitosis, 10–12 benign tumour, 129
iodine deficiency, 109 gut-associated (GALT), 84, 91 spermatogonium, 115, 115–16 myosin, 7
138 INDEX
muscle, 7, 26 oxyphil cell, 109 prophase, 10 serous gland/cell

skeletal, 27, 28 oxytocin, 108, 128 oogenesis, 124 salivary gland acini, 84, 85
spermatogenesis, 115 tongue, 85
N P prostate, 119–20 trachea, 78
protein, cytoplasmic, 9 serous membrane/serosa, 18, 134
nasal cavity/sinuses, 78 Pacinian corpuscle, 37, 47 protein fibre, extracellular matrix of alimentary canal, 84
nasopharynx, 78 pancreas, 17, 92–5, 110–11 connective tissue, 22 stomach, 86
natural killer (NK) cell, 51 pancreatic duct, 95 pseudostratified epithelium, 15 uterine tube, 127
neonatal respiratory distress Paneth cell, small intestine, 88 respiratory system, 15, 77 uterus, 128
syndrome, 82 papilla, 134 pseudounipolar neuron, 34, 35 Sertoli cell, 116, 117–18, 118
neoplasms see tumours lingual, 85 psoriasis, 48 sex hormone (adrenal), 111
nephron, 98–102 papillary layer, 45 puberty, sickle cell anaemia, 50
nerve paracortex, 56 female, 123 sinus, paranasal, 78
impulse (and its transmission), paracrine gland, 17 male, 115 sinusoid,
34, 37 parafollicular cell, 108–9, 109 pulmonary vessel, 69, 70 capillary 74–5
supply paranasal sinus, 78 Purkinje cell, 70 liver, 92
muscle, 31, 37 parasympathetic nervous system pyloric region, 86 skeletal muscle, 26, 27–8, 31
pituitary, 107, 108 bronchus, 79 collagen, 27, 61
skin, 47 bronchiole, 80 R contraction, 27, 36
nerve tissue and nervous system, ganglion, 38 hypertrophy and hyperplasia, 31
13, 33–41 nerve, 39 receptor, sensory, 35 repair, 31
neuroendocrine cell (in epithelium), penis, 121–2, 122 receptor-mediated endocytosis, 8 skin, 42–8
134 parathyroid gland, 109 rectum, 91 connective tissue, 22
respiratory tract, 78 parathyroid hormone, 62, 109 red blood cell (erythrocyte), 49–50 epithelium (= epidermis), 15, 18,
small intestine, 88 parietal cell, 87 synthesis in marrow, 53 42–5, 47
stomach, 87 parotid gland, 84, 85 red pulp, 55 Langerhans cell, 44, 53
neurohypophysis, 106, 107, 108 pars distalis, 107 renal corpuscle, 99 sensory receptor, 35, 47
neuron, 33–6 pars nervosa, 108 renal pelvis, 97, 103 small intestine, 3, 87–91
functional variation, 34 penis, 114, 121–2 renin, 103 parasympathetic ganglia, 39
locational variation, 34–6 periarteriolar lymphatic sheath, 55 repair smoking, 82
shape variation, 33–4 pericardium, 71 epithelium, 20 smooth endoplasmic reticulum, 8
neurotransmitter, 36–7 perichondrium, 59 skeletal muscle, 31 muscle (sarcoplasmic reticulum),
neutrophil, 51 pericyte, 26, 74 reproductive system, 114–32 26
Nissl granule, 33 perikarya, 33, 37, 38 female, 123–32 smooth muscle, 26, 30, 31
node of Ranvier, 34 perimetrium, 128 male, 114–22 gastrointestinal tract, 84–92
noradrenaline (norepinephrine), perimysium, 27 respiratory distress syndrome, oesophagus, 85
111 perineurium, 39 infantile, 82 bladder, 104
nucleolus, 6 periosteum, 61, 65, 66 respiratory system/tract, 77–82 bronchus, 79
nucleus peripheral nervous system (PNS), epithelium, 15, 77–8, 80, 81 bronchiole, 80
cell, 6 33, 34, 39 function, 77 contraction see contraction
in central nervous system (CNS), peristalsis, 84 lower, 81–2 cutaneous, 47
37 large intestine, 91 upper, 77–80 ductus deferens, 119, 122
peritoneum, 84, 134 rete testis, 118 hypertrophy and hyperplasia, 31
O stomach, 86 reticular connective tissue, 22, 23–4 prostate, 119, 120
Peyer’s patch, 91 reticular layer, 45 vessel, 72, 73
oedema, 76, 134 pharynx, 78, 85 reticulin and reticulin fibre, 23–4 sodium ion, renal handling, 102
oesophagus, 85–6 pineal gland, 112 liver, 22, 23, 92 somatic nervous system, 33
oestrogen, 128, 131 pituitary gland, 106–8 rheumatoid arthritis, 68 efferent neuron, 36
menstrual cycle, 125, 129, plasma cell, 21, 51, 52, 56 ribosome, 8 somatotrophin, 107
130 plasma membrane, 6 RNA, 6, 8 space, real/artefactual, 3
oligodendrocyte, 38 platelet (thrombocyte), 52 rough endoplasmic reticulum, 8 spermatozoon, 9, 12, 114, 114–16
oocyte, 124–126 synthesis, 53 rugae, gastric, 87 ejaculation, 118, 119, 120, 121,
oogonium, 123 pleura, 77 122
oral cavity, 84 pneumocyte, 81 S fertilisation by see fertilisation
organ, 134 podocyte, 99 production, 114–16
recognising, 19 polymorphonuclear leucocyte, 51 S phase, 10 spinal cord, 39
organelle, 5, 7–9, 134 portal tract, 92 saliva, 84–5 ganglion, 37
oropharynx, 78 pregnancy, ectopic, 128 salivary gland, 84–5 sensory neuron and information,
ossification, 63, 64–6 preservation, 1 sarcolemma, 26, 28 35, 36
osteoarthritis, 68 prickle cell, 44 sarcomere, 28 spleen, 54–5
osteoblast, 61–2, 65 primary follicle, 124 sarcoplasm, 26, 27 spongy (cancellous) bone, 62–3, 63
osteoclast, 62, 66 primary tissues, sarcoplasmic reticulum, 26, 28 squamous epithelium
osteocyte, 62, 63 connective, 21–25 satellite cell, 37 simple, 14
osteogenic cell, 65 epithelial, 13- 20 Schwann cell, 34, 39 stratified, 15
osteon, 63 muscle, 26–32 sebaceous gland, 45–6 tongue, 85
osteoporosis, 68 nerve, 33- 41 secondary follicle, 125 vessel see endothelium
osteoprogenitor cell, 61, 66 primordial follicle, 124 sectioning, 2 staining, 2
ovary, 123–6 progesterone, 128, 130, 131 processing for, 1–2 stem cells
ovulation, 126 menstrual cycle, 129, 130 seminal vesicle, 120 gastric epithelium, 87
ovum, 123 prolactin, 107, 130, 131 seminiferous tubule, 114–15 haematopoietic, 53–4
fertilisation see fertilisation proliferative phase of menstrual ducts draining, 118 small intestine epithelium, 88
formation, 123–5 cycle, 129–30 sensory (afferent) neuron, 34–5 steroid hormones
oxyntic cell, 87 prometaphase, 10 skin, 35, 47 adrenal, 110, 111
Index 139
female, 125,126, spermatogenic cell, 115 tubular pole, Bowman’s capsule, 99 vas deferens, see ductus deferens
male, see Leydig cell tendon, 23, 27 tubule, renal, 101 vascular pole, Bowman’s capsule, 99
stomach, 86–7 collagen, 27, 61 tumours, 20, 134 vasculature see blood vessel
ulcer, 88 terminal bronchiole, 80–1 cervical, 130 vasopressin (antidiuretic hormone),
stratified (compound) epithelium, terminal hair, 46 malignant see malignant tumours 102–3, 108
13, 15–17 testis, 114–18 nervous tissue, 40 vein, 69, 71, 75
testis, 23 basement membrane and skin, 48 disorder, 76
tongue, 85 stratified epithelium, 23 uterine, 130 wall, 72, 75
stratum corneum, 42–4, 45 ducts draining, 119 tunica adventitia, 72–3, 73 vellus hair, 46
stratum germinativum, 44 testosterone, 117, 118, 119 tunica albuginea, 121 ventricle (heart), 69, 70, 71
stratum granulosum, 44 theca interna and externa, 125 tunica intima, 72, 73 venule, 69, 71, 75
stratum lucidum, 44 thin (micro)filaments, 7 tunica media, 72, 73 vesicle, 8
stratum spinosum, 44 thrombocyte see platelet villi, small intestine, 88–90
striated (striped) muscle, 26 thrombosis, deep vein, 76 U vitamin C deficiency, 22
stromal cell, ovarian, 125 thymus, 54 vocal fold/cord, 78
sublingual gland, 84, 85 thyroglobulin, 108, 109 ulcer, stomach, 88
submandibular gland, 84, 85 thyroid gland, 108–9 ultrastructure (electron microscopy), W
submucosa, alimentary canal, 83, 84 thyroid-releasing hormone (TrH), 5, 6–10
suprarenal (adrenal) gland, 24, 107, 109 skeletal muscle and contraction, water, renal transport, 101
109–11 thyroid-stimulating hormone (TSH), 28 wax embedding, 1–2
sweat gland, 17, 45 107, 109 ureter, 103–4 white adipose tissue, 24
sympathetic nervous system thyroxine, 109 urethra, 104 white blood cell (leucocyte), 21,
arteriole and, 73–4 tight junction, 9 female, 104 51–2
bronchus and, 79 tissue, 13–41, 134 male, 114, 120–1 disorder, 52
bronchiole and, 80 preservation, 1 urinary tract/system, 97–105 synthesis in marrow, 53
ejaculation and, 122 primary, 13–41 transitional epithelium, 15,17, 103 white matter
ganglion, 38 processing for slicing, 1–2 uriniferous tubule, 101 brain, 39
nerve, 39 recognising, 18–19 urothelium (transitional spinal cord, 37, 39
skin, 47 sectioning, 2 epithelium), 15–17, 103, 104 white pulp, 55
synapse, 36–7 staining for visualisation, 2 uterine tube, 126–7
synovial joint, 59, 134 tissue fluid, excess accumulation uterus, 127–9 Z
(oedema), 76, 134
T tongue, 85 V zona fasciculata, 110
skeletal muscle, 29 zona glomerulosa, 110
T cell/lymphocyte, 51 tonsil, 57, 85 vagina, 130 zona occludens, 9
lymph node, 56 trachea, 78–9 epithelium, 16, 130 zona pellucida, 125
production, 54 transitional epithelium, 15–17, 103, valve zona reticularis, 110
spleen, 55 104 heart, 71 zonula adherens, 10
thymus, 55 transverse fold, small intestine, vein, 75 cardiac muscle, 30
telophase, 11 88–90 varicose vein, 76 zymogenic cell, 87
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Histology

AN ILLUSTRATED COLOUR TEXT

Commissioning Editor: Timothy Horne

Barry S Mitchell BSc PhD MSc CSci FIBMS CBiol FIBiol

Sandra Peel BSc PhD DSc

No part of this publication may be reproduced or transmitted in any

First published 2009

British Library Cataloguing in Publication Data

Library of Congress Cataloging in Publication Data

Working together to grow

3. Primary tissues 1: epithelial tissue 13

4. Primary tissues 2: connective tissue 21

5. Primary tissues 3: muscle tissue 26

6. Primary tissues 4: nerve tissue 33

8. The blood and immune system 49

9. Bone and cartilage 59

10. The circulatory system 69

11. The respiratory system 77

12. The digestive system 83

13. The urinary system 97

14. The endocrine system 106

15. The male reproductive system 114

16. The female reproductive system 123

Cell with densely stained Illustrations in this book

Red blood cell

‘Empty’ cytoplasm of adipocytes c

fat occupies most of the cytoplasm.

Cytoplasm of adjacent cell

Fig. 2.1 Electron micrograph of a cell. Low magniﬁcation.

Ultrastructure of cells and

Nucleus and nucleolus

Outer membrane of mitochondrion

Fig. 2.6 Endocytosis, exocytosis, and function

Cytoplasm at apices of cells ■ Tight junctions (zona occludens). In

■ Desmosomes (macula and zonula Tight junction 1h G0

Cell membrane Cytoplasm

Homologous pair X chromosome

Represents old DNA in a chromatid

the cytoplasm and it is known as the

Some cells may suspend their progres-

gression around the cycle, undergo dif- synthesis

females and spermatozoa in males. (endocytosis) and export of substances (exocytosis)

normal number of chromosomes (and adding, for example, carbohydrates

detecting some sensations. Although ■ compound (stratified) epithelia, which

■ simple squamous Connective tissue

Simple squamous epithelia

Simple columnar epithelia

from abrasion. The squamous surface

Fig. 3.5 Pseudostratiﬁed columnar Connective tissue

Epithelial cell nuclei

Ciliated columnar epithelial cell

Fig. 3.6 Stratiﬁed squamous epithelium

Squamous epithelial cell nucleus

Squamous epithelial cell nucleus

■ exocrine glands that secrete their

Other secretory gland cells are present

■ merocrine secretion (Fig. 3.10A) involves

A C specialised epithelial cells surround the

Lumen of blood vessel (vein)