BBMS1001

Cell structure
Cell membrane
Integral/intrinsic:
- Extend deeply into membrane, often extending from one surface to the other
- Form channels through the membrane
Peripheral/extrinsic
- Attached to integral proteins at either the inner or outer
surfaces of the lipid bilayer
- Non-gated ion channels: always open
- Gated ion channels: can be open or closed
- Ligand gated ion channel: open in response to small
molecules that bind to proteins or glycoproteins
- Voltage-gated ion channel: open when there is a change
in charge across the plasma membrane

Receptor protein
Can attach to specific ligand molecules and act as an intercellular communication system

Endocytosis: internalisation of substance -> Phagocytosis, Pinocytosis, Receptor mediated endocytosis

Exocytosis: Similar to endocytosis but occurs in opposite direction

Cytoplasm composted of cytosol, organelles, cytoskeleton

Nucleus: largest organelles

nuclear envelope contains pores used for
- passive diffusion of small molecules (sugars, nucleotides, amino acids)
- actively importing proteins into the nucleus
- actively exporting RNAs and proteins from the nucleus
nuclear pore complex at nuclear pore are symmetrical in structure
Proteins are selectively transported into the nucleus through nuclear pores
Mature nuclear proteins contain sequence information required for their nuclear localization
Information for nuclear import lies in a small portion of the transported protein
Chromatin: DNA complexed with proteins (histones)
Chromatin-> chromatids-> chromosomes
During interphase, the general mass of chromatin is in the form of euchromatin, which is less tightly packed
than mitotic chromosomes.
Regions of heterochromatin remain densely packed throughout interphase.
 - Chromosome decondensation at reformation
of nuclear envelop, cytokinesis
- Chromosome condensation at nuclear envelop
breakdown, chromosome segregation

Nucleosome
Nucleosomal DNA is divided into:
- core DNA: 146 bp
- linker DNA: 114 bp
H1 is associated with linker DNA and may lie at the point where DNA enters or leaves the nucleosome.

Histone octamers (nucleosome) are displaced and reassembled during transcription

- most transcribed genes in nucleosomal structure
1. nucleosome at specific specific location on RNA
2. RNA polymerase binds at promoter of RNA
3. RNA polymerase transcribes up to terminator of RNA
4. Nucleosome is displaced
5. Nucleosome reassembles at new position on RNA

Nucleolus
Extremely dense structure in the nucleus
- Site of ribosomal RNA transcription
- Processing of ribosome
- Ribosome assembly
- Location of ribosomal genes

Nuclear lamina
- Located beneath the inner nuclear membrane.
- Constructed of intermediate filament proteins
- Lattice structure, help form a nuclear cytoskeleton
- nuclear envelope assembly nuclear envelop
support
- can be anchored by lipid modification or
interaction with membrane proteins
Mitochondria
- Cristae: Infoldings of inner membrane
- Matrix: Substance located in space formed by
inner membrane
- Increase in number when cell energy requirements
increase
- Contain circular DNA (maternal origin) that codes
for some of the proteins needed for involved in
respiratory system
ER
- Cisternae: interior space inside ER (isolated from
cytoplasm)
- sarcoplasmic reticulum for calcium storage and
release

Golgi apparatus (protein sorter)

- Modification, packaging, distribution of proteins and

lipids for secretion or internal use
- Contain cisternae
- Cis (forming), trans (maturing) faces
- For packaging of proteins (from rough ER)

Lysosomes Peroxisomes
- Membrane bounded - membrane bounded
- Degradation of phagocytosed materials - smaller than lysosome
- Destruction of organelles (autophagocytosis) - Contain enzymes to break down
- lysosomal enzymes (mostly active at acidic pH): fatty acids and amino acids
Lipase and esterase - Hydrogen peroxide is a by-
RNAse and DNAse product
Cathepsins and other peptidases, acid hydrolases - Common in liver cells

Cytoskeleton
- internal framework of filaments
- determine cell shape
- Provides an organizing template for many activities, eg. anchoring organelles in place and transport of
organelles, vesicles and macromolecules
- Allow for movements eg. changes in cell shape, movements of cilia, cell division

- Microtubules: hollow, polymers of tubulin subunits

->Internal scaffold, intracellular transport (organelles,
vesicles, chromosomes, pigment), cell div (chromosomes
segregation)
- composed of  and  tubulin proteins
- flagellar & ciliary movement
- function in concert with molecular motors (kinesins (+) &
dyneins(-)) generating force & move vesicles and other
complex along microtubule surface
- Microfilaments: actin.
->Structure, support for microvilli, contractility, movement
- formed by polymerisation of actin proteins.
- negative (minus) end: actin bound to ADP, positive end bound of ATP
- different distribution in different part of cells
-> microvilli (draw)
- containing actin microfilament
- increase surface area
- X move
-> Cell migration: microfilaments as stress fibres for moving (draw)
-> Cytokinesis (cytoplasmic division after cell div): microfilaments form contractile ring (draw)

- Intermediate filaments: Mechanical strength

- Intermediate filament subunits assemble with high affinity into strain-resistant structures.
- Intermediate filament assembly is rapid and requires no additional factors
-> Dimer (2 monomers) formation by leucine zipper
- strain hardening under stress -> stronger than actin filaments / microtubules
-> in cell junction (connect cells tgt, when stretching, these cells won’t collapse)

centrosome (microtubule organizing centre (MTOC))

- Composed of 2 centrioles (microtubules) surrounded by pericentriolar materials (proteins)
- Define the poles of the spindle and play a role in spindle formation (mitotic spindle)

- Centriole duplication is controlled by the cell cycle and is coordinated with DNA replication

- Centrosomes nucleate microtubules and often remain bound to their minus ends
 Inside minus end, outwards positive end

-> Cilium (9+2 douplets) : contains microtubules / centriole structure

- project from cell surface
- attached to membrane through basal body (9 triplets)
- can move (sliding of microtubules when provide ATP
moves materials over cell surface
-> formation of basal body of cilium by centriolar / acentrolar pathways
Cell cycle
4 cycling phases **irreversible order**:
1. M phase: mitosis (nuclear div, cytokinesis) -> prophase, metaphase, anaphase, telophase
2. 1 phase: cell growth, organelle duplication, protein synthesis
3. S phase: DNA synthesis
4. G2 phase: centriole replication completed, ready for mitosis
Cyclin-dependent kinase (CDKs)
} interphase

- Regulates cell cycle progression

- Activated only when complexed with a cyclin proteinoscillate (moving/ vibration) in abundance during cell cycle
- Diff cyclins & CDK at diff phases -> to phosphorylate distinct sets of target proteins

- CDK-cyclin complexes regulated by phosphorylation, inhibitory proteins, proteolysis, subcellular localization

Checkpoints ensure the error-free completion of cycle event before the next process begins
may be essential when cells are stressed or damaged
DNA replication and DNA damage checkpoints monitor defects in DNA metabolism
Incomplete / defective DNA replication activates cell cycle checkpoint
 DNA damage checkpoint stops the cell cycle
o DNA damage -> Arrests at G1 (start checkpt)
o DNA damage/ incomplete replication -> .. at S phase
o DNA damage -> .. G2 (G2/M checkpt)
 spindle assembly checkpoint (SAC) monitors defects in chromosome-microtubule attachment.
 Mitotic spindle attaches to kinetochore
 Prerequisite for chromosome segregation: proper attachment of microtubules to kinetochores
o Unattached kinetochore -> .. Mitosis (metaphase-anaphase transition checkpt to prevent errors in
sister chromatid separation)
Cells may withdraw from cell cycle Meiosis
cell div controlled by external stimuli & nutrient availability -> not continuous
non-proliferating state (X increase no of cells) = quiescence / G0
cells can permanently leave the cell cycle -> become senescent
cell death
- necrosis: cell swellscell burstsinflammatory response follows
- Apoptosis
 Programmed cell death
 normal homeostasis, inhibition of cancer & disease processes (eg. viral infection)
 most animal cells contain molecules that can cause death by apoptosis
 activated by appropriate stimuli
 breakdown of nucleus of cell
o Nuclear envelope breakup -> nuclear fragmentation, blebbing -> cell fragmentation -> phagocytosis of
apoptotic body (the dying cell) by phagocytic cell
Death receptor (Extrinsic) pathway
o death receptor pathway of apoptosis transmits external signals
o binding of specialized ligands in the tumour necrosis factor (TNF) family to death receptors  Caspase
activation  apoptosis
 Mitochondrial (intrinsic) pathway
o most apoptosis in mammalian cells: pathway in which mitochondrial outer membranes are disrupted ->
release contents from mitochondrial intermembrane into cytosol
 ** mitochondrial outer membrane permeabilization (MOMP)
o Bcl-2 family protein mediate & regulate MOMP & apoptosis
 3 classes of Bcl-2 proteins that induce, directly cause, inhibit MOMP
anti-apoptotic Bcl2 protein (with BH1234) (eg. Bcl2, Bcl-X)
 Pro-apoptotic BH3-only protein (eg. Bad, Bim, Bid, Puma, Noxa)
 activate Bax & Bak
interfere with anti-apoptotic Bcl2 protein fuctions
 Pro-apoptotic BH123 protein (eg. Bax, Bak)
 essential for MOMP by directly causing membrane disruption
 o Then, cytochrome c is released to induce caspase activation
 Holocytochrome c binds and actiavate cytosolic
apoptotic protease activating factor-1 (APAF-1),
which binds and activates inactive caspase-9.
Caspases orchestrate apoptosis by cleaving (cut 出嚟)
o
specific substrates
 Initiator: caspase-8, -9 executioner: capases-3, -6,
-7
o Initiator caspases are activated through dimerization by
adaptor molecules that contain protein-protein interaction
death folds
activate dimer cleaves  cleavage activates executioner
caspases  apoptosis
 Death receptor pathway can engage MOMP through cleavage of protein Bid <-- link between 2 pathways
o Ligation of death receptor  activate caspases-8 cleaves Bid trigger Bax, Bak  MOMP

Cell communication
Cellular signalling -> chemical
Physical signals converted to chemical signal
- Endocrine signalling through blood stream
- Paracrine signalling: from one cell to **adjacent target cell** directly **more localised than endocrine
- Autocrine signalling: target sites on same cell (eg secret growth factor to self)
- Signalling by plasma membrane-attached proteins (immune cells: lymphocytes, T cells)

Receptors ->**catalysts & amplifiers

- Ligand-binding domain (extracellular space) & effector domain (cytosol) & trans membrane
o Same ligand can bind to diff receptors
o Same ligand binds to receptor with diff effector domain -> diff effects
o Increase rates of key regulatory reactions
o Active & inactive conformation: active in dimer / phosphorylated
- Cell-surface receptors (common果隻) receive hydrophilic signal molecules
- Intracellular receptors carrier protein brings small *hydrophobic signal molecule to intracellular receptor protein in
nucleus of target cell (nuclear receptor)
- Protein tyrosine kinase receptor
o The kinase domain at intracellular spaces (cytosol) (beneath cell membrane)
o protein-tyrosine kinases are activated by growth factors ->triggers proliferation & metabolism
o mutation may be oncogenic (cancer causing)  fast proliferation
o Signalling proteins bind to the phosphotyrosine residues of the activated receptor
o eg. Epidermal growth factor (EGF) receptor, insulin receptor
- Ion channel receptor -> very fast
o Rapid (microsecond) changes in membrane potential
o Selective channel
o Regulates intracellular conc of regulatory ions eg. Ca2+
- Common effector proteins: metabolic enzyme, gene regulatory protein, cytoskeletal protein -> altering cell shape
- Divergence: allows multiple responses to single signal & movement
- Convergence: allows signal integration & coordination

- 3 kinds of signalling circuit:

1) A-> response; B-> response; A or B can give
response
2) Only A-> X response; only B-> X response; need
BOTH A AND B to give response
3) Only A-> response; only B-> X response; A+B tgt->
B dilute effect of A
- **adaptive-> Feedback mechanisms
signalling molecules: proteins, ions, small molecules
second messenger: provide readily diffusible pathways for information transfer ->propagate signals between distant proteins
eg. CaMP, Ca2+, some lipid molecules
o lipid, lipid-derived second messengers produced in membranes
o Phospholipase C release soluble and lipid second messengers
 form Inositol 1,4,5-trisphosphate (IP3), DAG <- second messengers
Protein - protein interaction signalling
 - Preformed signalling complex (intracellular signalling proteins) on a scaffold protein
- Signalling protein regulated by protein-protein interaction
- Activating and deactivating reactions are separate and
independently controlled (like switching on / off reaction)
 Executed by diff regulatory proteins
 Allows fine-tuned regulation of amplitude and timing
- Signalling uses both allostery & covalent modification
o Allostery: ability of a molecule to alter the conformation
of a target protein when it binds non-covalently to that
protein (some activator and inhibitor)
 Protein phosphorylation
o Protein kinase phosphorylate Ser and Thr, or Tyr 
these contain hydroxyl grp for phosphorylation
-> phosphate from ATP -> form phosphorylated protein & ADP
o Protein phosphatases -> reverse action of kinase (dephosphorylation), independently regulated!!
 Regulation of G protein by GTPase cycle
o G protein module = receptor + heterotrimeric G protein + effector protein
o G proteins convey signals by regulating the activities of multiple intracellular signalling
proteins -> effectors

1. Heterotrimeric G protein activated when

G binds to GTP & + extracellular signal
molecule
2. GTP hydrolyse to GDP -> inactivates G
protein
** with GTP-> activated; GDP ->inactivated
GTP hydrolysis is slow

o Protein phosphorylation is faster than gene

modifying signalling

Tissue -> grp of cells organised to perform specific function

Endoderm (lining of digestive tract, derivatives, sth soft), mesoderm (muscles, bones, blood vessels), ectoderm (skin,
neurotoderm)

Tissue classification by cell structure, composition of non-cellular extracellular matrix, cell function
4 classes:
- epithelial tissue: cover body surfaces, line body cavity, lining of digestive, respiratory, urogenital systems, glands,
heart & blood vessels)
o free, basal (anchorage to basement membrane), lateral surfaces
o basement membrane: **extracellular formed by secretions of both epithelium & connective tissue
 attachment to connective tissue
 guide cell migration during tissue repair
 filter in nephron in kidney
 **not every epithelium with base membrane
o avascular (no blood vessels here nutrients from blood supply at the connecting connective tissues)
o mitosis
o eg. epithelia: protection, barriers, passage of substances (eg. Nephrons in kidney), secretion (pancreas),
absorb substances (small intestinal lining)
cell surfaces:
 smooth: reduce friction
 microvilli:  surface area for absorption/ secretion (stereocilia-> elongated microvilli
 cilia: move materials across surface for sensation/ absorption)
 folds: in transitional epithelium for changing shape, urinary system
no of layers of epithelial cells:
 simple-> 1 layer of cells extended from basement membrane to free surface
for diffusion of gases, filtration of blood, secretion, absorption
 stratified-> more than 1 layer, apical cell layers (upper layer) change shape depending on organ
distention (growth)
 protection more layers-> strength (esp against abrasion磨損)
  pseudostratified-> look like stratified but actually simple layer
shape of cell
 squamous: flat, scale-like for diffusion, filters
 cuboidal: ~equal height & width
 columnar: tall like column } secretion/ absorption;
may include goblet cell to produce & secret mucus
simple squamous epithelium: blood & lymph vessels, air sac, loop of Henle in kidney tubules
simple cuboidal: kidney tubules, gland & its duct, choroid plexus of brain, terminal bronchiole lining, ovary
simple columnar: glands & ducts, bronchiole, uterus, uterine tube, alimentary canal (from stomach) surface
ovary tube (movement of oocytes by ciliated cells)
stratified squamous: cuboidal at basal layer, progressively flatten towards surface (squamous)
in moist -> surface cell with nucleus & cytoplasm; keratinized角質化-> surface cell dead
upper alimentary canal, anus, vagina, inferior urethra & cornea, keratinized skin
stratified cuboidal: multiple layers of cuboidal cell
sweat gland ducts, salivary gland ducts, ovarian follicular cells
stratified columnar: columnar cells on cuboidal cells
mammary gland duct
pseudostratified columnar: lining of upper respiratory track (till brochi)
**transitional epithelium: stratified, changing shape lining of urinary bladder, ureter, superior urethra to hold
urine
cell connection on epithelium on lateral & basal surface of cells
 form permeability layer, bind cell tgt, provide mechanism for intercellular communication
 cell-to-cell: occluding junction (tight junction)-> holds cell tgt, form permeability barrier
zonula occludens-> impermeable barrier, chemicals X pass between cells
communication junction (gap junction)-> protein channels for intercellular communication
eg. Ions & small molecules passing through, coordinate cardiac & smooth muscle,
movement of cilia
anchoring junction (zonula & macula adherens = desmosomes)
zonula adherens-> between adjacent cells, weak holding cells tgt
desmosomes-> disk shaped regions of cell membrane at area of stress
contains adhesive glycoproteins, *intermediate protein filaments extend to cytoplasm
 cell-to-extracellular matrix: anchoring junction (focal adhesion, hemidesmosome)

glands: endocrine & exocrine (with ducts)

 unicellular (eg goblet cells), multicellular
 simple: ducts with few branches; compound: many branches
 tubular/sac like structure duct ends= acini (eg pancreas)
 simple sac duct ends= alveoli in lungs
secretion method:
 merocrine: X cytoplasm loss, secretion leaves by active transport / exocytosis (eg sweat glands)
 apocrine: fragments of gland go into secretion, apex (top) cell pinches off (eg mammary glands)
 holocrine: whole cell secreted-> cell burst & die (eg sebaceous glands)
- connective tissue (CT): support of other tissues
o abundant, in every organ
o consists of cells separated by extracellular matrix
 enclose organ as capsule, separate organs into layers  fat storage
 connect tissue (tendon & ligaments)  fat as cushion & insulate
 support & movement (bone)  transport: blood  protect: cells of immune system
 adipocytes: common in skin dermis, rare in cartilage
 mast cells: common beneath membranes, along small blood vessels, release heparin, histamine,
proteolytic enzyme in response to injury
 WBCs: respond to injury/ infection
 Macrophages: phagocytize, provide protection (fixed: stay in position in connective tissue;
wandering: move by amoeboid movement through connective tissue)
 Undifferentiated mesenchyme (stem cells): develop **adult stem cell**

In extracellular matrix…
o Protein fibres:
 Collagen: most common, strong, flexible, *inelastic
 Reticular: fill spaces between tissues & organs, form branching networks, fine collagenous
 Elastic: return to original shape after distension/ compression, contain elastin
o Ground substance:
 Hyaluronic acid: polysaccharide, lubricant, vitreous humour in eye
  Proteoglycans: protein & polysaccharide, protein attached to hyaluronic acid, trap  amount of
 Adhesive molecule: hold proteoglycan aggregates tgt water
chondronectin in cartilage, osteonectin in bone, fibronectin in fibrous CT
Adult connective tissue:
 loose (areolar): loosely arranged collagenous fibre
 Attaches skin to underlying tissue
 Contain collagen, reticular, elastic fibres, all 5 types of cells
 Often associate with other CT (eg reticular tissue, fat)
 dense: fibres from thick bundles fill most extracellular space (dense regular & irregular)
dense regular collagenous connective tissue-> resist stretching (tendons, ligaments)
dense regular elastic-> collagen gives strength, elastic makes more prevalent. (ligaments in vocal folds &
dense irregular collagenous-> protein fibres arranged in random network nuchal (neck))
form innermost layer of dermis, capsules of kidney & spleen
dense irregular elastic-> bundles, sheets of collagenous & elastic fibres oriented in multiple directions,
strong, elastic (walls of elastic arteries)
adipose-> adipocytes as predominant cells
yellow (white): abundant, widely distributed, white at birth, yellow with age
brown: in axillae (armpit), neck, near kidneys
reticular-> form superstructure of lymphatic & haemopoietic tissues, fine reticular fibres & cells networks
spaces between cells contain white cells & dendritic cells
- muscle tissue: contractile cells for movement
- nerve tissue: receive/ transmit /integrate info, control body activity
organisation of body
- skeleton: axial, appendicular
- cavities: cranial, thoracic, abdominal, pelvic

cell lineage & differentiation

Cell Lineage: the developmental history of a cell from its birth until its final division and differentiation into a particular
cell type (cell fate)
Cell Differentiation: Acquisition of specific structural, functional and biochemical properties that allow cells in a
multicellular organism to perform specific functions in a variety of tissues and organs
Fate map: A diagram that shows the developmental fate of various cells from an embryo at early stage of development 
can be found by lineage tracing
- dye labelling
o lipid soluble dyes: Dil (green), DiO (orange) into cell membrane with high intensity of fluorescence
o disadvantage: label will be diluted upon cell division and therefore little use for long-term lineage analysis
- retrovirus infection (permanent dying)

o retroviral genome (in single-stranded RNA)

 Long terminal repeat (LTR) (x2 at start & end of
RNA): initiation of genome expression
 Group-specific (gag): structural capsid proteins
 Polymerase (Pol): reverse transcriptase (convert
RNA to cDNA), integrase, protease
 Envelope (Env): retroviral coat proteins

**then mark lineage tracing by Green

florescence protein

: cDNA integrated in nucleus of cell will be

*permanently there even other infections
occur
X: replication for infection continue in cell,
infect the parts that don’t want to be marked
 take away retroviral genome injection of
replication **incompetent retrovirus
factors of cell fate
- intrinsic program: gene expression patterns
- extrinsic cues/ signals: features in the environment to which a cell can respond with a change in potential fate, can
induce intrinsic changes
- Progenitor cells: descendants of stem cells with more constrained in their differentiation potential and proliferative
capacity (intermediates)
- Specification: Cell has been exposed to extrinsic cues and may have started a specific path of development, but a
change in the environment and genetic components can still alter the ultimate fate of the cell
- Determination (commitment): Cell has committed to a particular fate, which will be maintained even if the cell is
exposed to different extrinsic cues.

Multipotent state specification determination differentiation Embryonic stem cells: totipotent from morula,
------------------------------------------------------------------------> pluripotent from inner cell mass of blastocyst
good: can be isolated (expandable), long term
differential expression of transcription factors cultured, differentiated into cell types from 3
germ layers

Adult stem cell: limited self-renewal capacity,

multipotent, repair & renewal of damaged
tissue/cell (tissue homeostasis)
bad: Difficult to find/ extract from mature
tissue, limited longevity: difficult to maintain
culture in long periods

IPSC
: pluripotent, easy to maintain & grow, no
immunorejection
X: may retain memory of cell type of origin,
Habor disease- causing genes of donor, low yield
of differentiated cells, cancer causing
Want to skip the IPSC inducing pluripotent step
 lineage-specific reprogramming by
transcription factors, but  yield, efficiency
**Factors of specification & determination:
- Transcription factor: proteins that bind directly to specific DNA sequences and regulate the cell’s ability to
transcribe DNA into mRNA (i.e. gene expression)
o Diff transcription factor, diff binding, diff effect Eg. In liver progenitor
Activator: turn on expression Turn on liver forming protein expression
repressor: inhibition/ turn off irrelevant factors Turn off other non liver ones
o Need appropriate AMOUNT
too little-> can’t express actively
too much-> may cause cancer
- Asymmetric segregation of cellular determinants
o Cell cleavage or asymmetric division creates uneven distribution of cellular determinants:
• Cytoplasmic proteins and organelles
• Transcription factors (mRNA and proteins)
• Membrane proteins
- Cell signalling mechanisms
o Diffusible signals (eg morphogen)
**signal conc gradient give rise to diff cell types (can work at a distance)
 sonic hedgehog (Shh)
 eg. regulation of gene expression of 5-digit identity (no of fingers production)
 low level of Shh activate repressor  turn off gene expression
 high level activate activator
o direct contact between cells via transmembrane protein
 delta-notch signalling (delta: ligand, notch: receptor)
uniform signalling
Notch regulates delta, delta regulates notch  keep in eqm.
High level of notch in one cell  low level of delta in the
cell & vice versa
lateral inhibition
Nervous system
sensing changes to external/ internal stimuli, interpret, remember, response (muscular contractions, glandular secretions)
PNS can be divided into:
- afferent: bring sensory info towards CNS
- receptors: transform stimuli into action potential
o somatic sensory: skeletal muscle, joints, skin
o Visceral sensory: Smooth muscle, cardiac muscle, glands
o Sense organs: Eye, nose, tongue, and ear
- Efferent: carries motor commands from CNS
- Effectors: respond to CNS commands
o Somatic nervous system (Skeletal muscle contracts, voluntary/ involuntary)
o Autonomic nervous system (Visceral motor system, Smooth muscle, cardiac muscle, and glands,
Involuntary, Sympathetic and parasympathetic division)
parasympathetic vs sympathetic -> opposite response (eg. Contract vs relax, constrict vs dilate, stimulate
vs inhibit, slower heartbeat vs accelerate heartbeat) maintain balance
neurons **polarized cell**
- Electrical excitability respond to stimuli by producing electric action potential
- Conductivity
- Signal integration
- Electric potential to chemical signalling (neurotransmitter)
- wide variety of shapes depending location & function subtypes
cell body (soma): Integrating and converting incoming signals into membrane potential (difference in electric potential
between the interior and the exterior of a cell)
signal conduction
establish resting membrane potential
- differential Na+ & K+ conc maintained by voltage-gated channels (Na & K) and Na+- K+ pumps
- More Na+ outside, more K+ inside
- K+ diffuse faster than Na+ diffusing in more positive charges outside the cell
 channels are more permeable to K+ than Na+ (net loss of cations out of the cell)

persistent current through slowly closing K+ channel hyperpolarises membrane

towards eqm  Na+ channel return from inactivated stated to close state
Closure of Na+ & K+ channel returns membrane potential to resting value

Stimulation of membrane depolarization:

changes in membrane permeability to Na+ & K+
 Generation of graded potential reaches
threshold action potential

unequal distribution of Na+ & K+ across membrane is

maintained by Na+ -K+ ATPase (Pumps) **active transport
 pump out 3 Na+ , pump in 2 K+ (net loss of cations out of cell)
Org- protein inside cell (more negatively charged)
resting membrane potential: -70Mv
 Hyperpolarization

Gated ion channels: depolarization:

o Mechanical force (touch/ pressure) opening of mechanical gated ion channels
o Neurotransmitters open ligand gated ion channels
o Voltage gated Na+ & K+ channels to generate action potential
} receptor potential,
belong to graded
potential but not action
negative inside -> Na+ channel closed potential !!!
positive inside -> K+ channel opened
strong stimulus: frequent action potential (not amplitude!!)
even if generated graded potential, but if X reach action potential threshold-> no action potential produce-> ppl
action potential initiated at axon hillock near cell body can’t sense

- Myelinated rapid propagation of action potential

Prevent more leakage of ions along axon
- Node of Ranvier: where leaky channels & Na+ & K+ gated channels located
- saltatory conduction (jumping action potential)

**Axonal proteins synthesised in cell body

Transport is bi-directional
o Anterograde (kinesin-motor complex proteins) (forward):
Secretory proteins (neurotransmitters), transported into the axons
and dendrites

o Retrograde (dynactin-motor complex proteins) (backward):

delivery of neurotrophic factors to the cell body, Recycled cell
membrane

Neuronal microtubules (same as microtubules) but with Gamma-tublin ring complex for microtubule nucleation
Tau protein: microtubule- associated protein tau- MAPT)
binds to stabilise microtubules
deficiency: Alzheimer’s disease: short term mem, problem with language, X manage self care

multipolar: multiple dendrites with one long axon (vertebrate CNS) interneuron
bipolar: one dendrites, one axon (sensory neurone in eyes & nose) sensory neurone
unipolar: one axon, branching dendrites (sensory neurones in skin, join, muscles, internal organs)  motor
somatic motor: only stimulatory effect (neurotransmitter: ACh)
single neurone from CNS to effector organs, heavily myelinated axon (eg skeletal muscle)
autonomic: both stimulatory (ACh) & inhibitory effect (NE)
2 neurone changes from CNS to effector organ, lightly myelinated preganglionic axons
glial (glue) cell: provide nourishment & functional support to neurones (supporting cells)
In CNS:
- Astrocytes: star shaped, support between neurons & capillaries, supply nutrients, post-traumatic repair and scarring
processes
 - Microglia: resident macrophagesimmune defence in CNS, protect neurones by removing wastes/ debris
- Ependymal cells: lining of ventricles of brain, central canal of spinal cord, produce & circulate cerebrospinal fluid
- Oligodendrocytes: produce myelin sheath (myelination)
In PNS:
- Satellite cells: cover surface of neurone cell body in sensory, sympathetic & parasympathetic ganglia, support
nutrients, protective cushioning cells
- Schwann cells: produce myelin sheath

Neurological disorder
- Multiple Sclerosis
o Autoimmune disorder due to genetic
dysregulation of immune system
against own myelin
o Damaged myelin (plaques)
o Visual disturbance, limb weakness,
loss of coordination/ balance, Loss of
sensation, speech impediment, mental
changes (decreased concentration,
attention deficits, memory loss
- Parkinson’s disease
o X produce dopamine neurotransmitter movement disorder

reason not
skipping action
potential step
and only using
graded
potential ----->

eg block action potential by tetrodotoxin (TTX)

Synapse
Pre-synaptic terminals: Voltage-gated Ca2+ channels, Synaptic vesicles (packed with neurotransmitters)
Postsynaptic density: neurotransmitter receptors
1. action potential propagates in presynaptic neurone
2. voltage-gated Ca2+ channel opens -> Ca2+ flux into
presynaptic axon terminal
3. release neurotransmitter by exocytosis
4. neurotransmitter binds to postsynaptic receptor
5. specific ion channels open  EPSP / IPSP
EPSP: glutamate: influx of Na+ -> intracellular less
negative -> fire action potential
IPSP: GABA (Gamma-aminobutyic acid), Glycine: influx
of Cl- / efflux of K+ -> intracellular more negative
-> less fire action potential
Neuromodulator: modifies neurone response to
neurotransmitter (eg. Dopamine, serotine)
**slower acting than neurotransmitter
2 types of glutamate receptors
- ionotropic: ion channels opening upon binding to neurotransmitter
- metabotropic: G-protein coupled receptor (GPCR) indirectly regulating synaptic transmission through second
messenger (eg. cAMP, cGMP) ** neuromodulator (eg. Dopamine) work here**

** Synaptic potential (either EPSP or IPSP) are graded potential

 stronger stimulation, larger amplitude
EPSPs must summate to induce an action potential in the post-synaptic neuron (only when exceeding the -55mV threshold)
Summation: spatial & temporal
 activity at 2 different excitatory synapse on same postsynaptic neurone
 generate the 2 potential close enough (less distant)  larger action potential

electrical synapse: direct change of ions between cells through

gap junction
always reliable and more reliable than chemical synapse cuz
always response to ion conc change
synaptic strength can change synaptic plasticity efficacy of
neurotransmission at chemical synapses is not fixed
- strong synapse (more receptors & vesicles, larger space)
-> large EPSP-> action potential
- Weak synapse-> small EPSP -> X action potential
** weak synapse is not forever weak use the synapse more become stronger
repetitive learning  stronger synaptic connection  better memory
eg. long term potentiation (LTP) in the hippocampal CA1 neurons depends on NMDA receptor (one type of
glutamate receptor)
o Induction of LTP: requires NMDA receptors, which only open when bind to glutamate and the
postsynaptic neuron is depolarized (influx of Ca2+ and Na+, remove Mg2+)
Unconditioned stimulus: strong input
Conditioned stimulus: weak input
Both stimuli activate at same time -> open NMPD receptor at the synapse of weak input -> strengthening of
synapse from weak input
Affect or memory: emotion
Operant conditioning: dopamine
- Dopamine release from ventral tegmental area (VTA)
modulates function of hippocampus (involved in memory!!!)
- Cross talk between glutamate & dopamine
- modulate synaptic strength of glutamatergic synapse in hippocampus
affect learning & memory
- acute stress increases production of glucocorticoid
 Low level of glucocorticoid enhances synaptic transmission
**Chronic stress reduces complexity of dendrites and loss of synapses

CNS with 12 pairs of cranial nerves, 31 pairs of spinal nerves

Brian divided into cerebrum, diencephalon (near hypothalamus), cerebrum, brainstem (where Medulla oblongata obtained)

Subcortical nuclei (cluster of neurones): eg. Basal ganglia (basal nuclei)

Corpus callosum connecting 2 hemispheres!!
Cerebral cortex: sensing environment, integration & storage of info, motor functions
Somatosenation:
Touch (mechanoreception), body position (proprioception), temperature (thermoception), pain (nociception)
- send info to specific regions of cerebral cortex through spinal cord
**somatosensory cortex at parietal lobe**
axonal endings of specific somatic pathways grouped according to location of receptors
Most densely-innervated parts of the body represent the largest areas of the somatosensory cortex
**memory is widely distributed, not stored in one specific area!!!
- Stored in different cortical neurones processing specific info in association cortex
 Parietal association cortex: sensory guidance of motor
behaviour and spatial awareness
Temporal association cortex: recognition of sensory stimuli
and storage of semantic (factual) knowledge
Frontal association cortex: organizing behaviour and working
memory
Limbic association cortex: emotion and episodic memory

Hierarchy of motor control

Premotor area (premotor cortex) & supplementary motor area
(SMA) (motor planning and decision) [at frontal lobe]
primary motor cortex & brain stem  spinal cord

Basal ganglia (beneath cerebral cortex)

Receive inputs from all cortical areas and project to frontal cortical areas concerned with the planning of voluntary
movements
** substantia nigra: neurones that project to basal ganglia
Parkinson’s disease: cell death in substantia nigra which produces neurotransmitter dopamine
Resting tremor (shaking at resting state), slow movement (bradykinesia)

Cerebellum
- Provides timing signals to the cortex for precise execution of movement (integrate information from the
environment for executing intended movement)
- dysfunction: deficits in motor coordination (rapid movement), intentional tremor (with intension to do sth)
diencephalon
- thalamus (relay station for inputs to cerebral cortex part of Limbic System
- hypothalamus (body homeostasis) } - Emotional behaviour
- Motivational drives
electroencephalogram (EEG) - Learning
measure electrical activies of neurones in cortex Urbach- Wieth disease: damage of amygdala
rhythmic wake like pattern
distinct patterns in diff states of consciousness:
relaxed, alert, sleep
At hippocampus:
brainstem Declarative memory is impaired
- midbrain Non-declarative memory & working mem are
- pons not affected here
- medulla oblongata
control diff states of consciousness (reticular activating system (RAS))
receive multiple sensory inputs form diff sources
excite thalamus & cerebral cortex, maintaining their activity (arousal)
*reticular formation
3 broad columns along length of brainstem: raphe nuclei, medial
(large cell) group, lateral (small cell) group

widespread & diffuse projections (ideal for arousal of whole brain)

secrete neuromodulators: norepinephrine, serotonin, acetylcholine
if the projection pathway is blocked-> coma
Muscle contraction
**Somatic voluntary: skeletal muscle
autonomic involuntary: smooth muscle, cardiac muscle, glands
neuromuscular junction
1. Acetylcholine (ACh) release from motor neurone
2. bind to receptor at motor end-plate
3. Na+ influx
4. End-plate potential (depolarization)
5. Action potential along membrane and down transverse tubule (T tubule: extensions of cell membrane
(sarcolemma) at terminal cisternae of sarcoplasmic reticulum (forming triad)
 carries electrical impulse to interior muscle cell) of muscle fibre
Sarcomere: basic functional unit of a muscle
Sarcolemma: plasma membrane
Sarcoplasm: cytoplasm

When contracting:
Sliding filament theory
- Z lines move closer to each other
- I band: thin filament + titin shortening
- A band: overlap of myosin & actin filament till same length
** exposure of myosin-binding sites on actin -> formation & detachment of
cross-bridge

action potential travels down T tubule

 depolarization of T tubule
 **For skeletal muscle: DHPR & RyR changes in conformation -> RyR on sarcoplasmic reticulum (SR) more permeable
to Ca2+
**For cardiac muscle: Calcium-induced calcium release (CICR), DHPR as voltage-gated Ca2+ channel
T tubule membrane depolarized-> Ca2+ enters cytoplasm via DHPR-> -> RyR on sarcoplasmic reticulum (SR)
more permeable to Ca2+
release Ca2+ from SR to cytoplasm through RyR
 binding of Ca2+ to troponin
 change tropomyosin position (tropomyosin rotates-> unblock actin site)
 exposure of myosin-binding sites on actin
APT -> energy for contractile activities: initiates cross-bridge formation (hydrolysis), breaks cross-bridge (by
binding to myosin)
strong binding between actin & myosin filaments
Myosin head energised by ATP being hydrolysed -> binds to exposed actin sites -> pull actin filament towards M
line (ADP & Pi released) -> myosin head separated from actin by ATP binds
 muscle fibre contraction-> shorten
Relaxation:
 Acetylcholinesterase decompose ACh, muscle fibre membrane not stimulated
 SR recaptures Ca2+ by active transport Sacro/endoplasmic reticulum Ca2+-ATPase (SERCA)
 ATP cause linkages between actin & myosin filaments breaking without ATP breakdown Cross-bridge recock (Cross
bridge detachment)
 troponin & tropomyosin inhibit interaction between myosin & actin filaments
 remain relaxed -> not shorten

motor unit = 1 motor neurone + connecting muscle fibres

muscle controlling fine movements contain small motor units
large weight-bearing muscle contain large motor units

muscle fibres from motor unit are spread throughout the muscle  activation of single motor unit causes contraction of
entire muscle

muscle twitch: muscle response to one stimulus Contraction – cross bridges

actively form & muscle shortens

Relaxation – Ca2+ is reabsorbed

into SR  muscle tension returns
to baseline

response graded by changing strength of stimulus, frequency of stimulation

frequently delivered stimuli:
- Muscle X have time to completely relax
- Increase in contractile force (wave summation)
o Increase contraction responding
multiple same strength stimuli
 Treppe (Staircase) effect
 Increase availability of Ca2+ in
sarcoplasm
 Heat generation -> higher
enzyme activity
** force of contraction  with no of activated muscle fibres, size of muscle fibres
muscle fatigue
- Neural fatigue: reduction on signals generated by nerve to trigger contractile response by muscle fibres
- Metabolic fatigue:
o ATP production by muscle X keep pace with energy demand
o Lactic acid accumulates
o Ionic imbalance of muscle

Smooth muscle
- Mostly in walls of hollow organs,
tubes: arteries (except heart)

- Cells arranged in sheets

- Spindle shaped
- Single nucleus
- X sarcomere, T tubule, visible
striations
- Contain actin & myosin
filaments
- Sliding filament mechanism
 Multi unit: vascular muscle, internal eye muscle single unit: visceral (internal organ) muscle
o Form motor units with rich nerve innervations - X form motor unit
(single neurone to individual smooth muscle cell) - More spontaneous action potential
 Varicosities (bulbous swelling) on single - A nerve fibre passes through tissue
nerve ending of autonomic neurones without contacting with any specific
release neurotransmitter into diffuse cell  many cells are stimulated
junction (synaptic cleft)
o Infrequent spontaneous action potential simultaneously
o Rare gap junctions - Electrically coupled by gap junctions
o Independent muscle fibres - Contract rhythmically as **one unit**
o **allow fine control & gradual response - **whole muscle contract/ relax

sources of Ca2+: SR, extracellular fluid (for prolonged contraction) (through ligand gated, voltage gated channels)
caveoli: infoldings at plasma membrane, regulating activity of Ca2+ channels involved in contraction
1. Ca2+ release from SR & extracellular into cytosol
2. Ca2+ binds to calmodulin, activating it -> activate kinase
3. Activated kinase transfer phosphate from ATP to myosin by ATPase ( myosin is active only when sufficient
Ca2+)
4. Phosphorylated myosin forms cross bridge with actin ->shortening
Muscle relax when Ca2+ level , myosin dephosphorylated

**actin & myosin filaments arrange diagonally -> smooth

muscle cells contract in corkscrew manner
- Actin filaments are anchored to dense bodies inside the
cell
- Some dense bodies at the cell membranes of adjacent
cells are links by protein bridges, which transmit the
contractile force from cell to cell

Smooth muscle contractile activity influenced by

- neurotransmitter from varicosities (acetylcholine,
norepinephrine)
- hormones (endothelin)
- electrical activity in plasma membrane of muscle cell
*smooth muscle cells can generate action potential upon membrane depolarization although X specialised end-plate
region
*pacemakers can generate own action potential spontaneously without external stimuli  still contract in absence
of action potential
reflex-> automatic
can be inborn or learned (acquired reflexes eg. Stepping brake when see red traffic light)
cranial reflexes eg. Movement responding to sudden loud noise
somatic reflex, autonomic reflexes (smooth muscle, glands)
proprioceptors in skeletal muscle:
- muscle spindle (detect change in muscle length, receptor for stretch reflex)
o stretching muscle-> activates muscle
spindle ->  rate of action potential in la
fibres

o contracting muscle-> reduce tension

in muscle spindle ->  rate of action
potential in la fibres
o monosynaptic

eg. Patellar reflex (knee-jerk reflex)

***Reciprocal inhibition: To accommodate
contraction of the agonist homonymous
muscle, antagonistic muscle (on the other
side of the joint) must be inhibited to prevent
it from working against the homonymous
muscle through inhibitory interneuron to
antagonist
 - golgi tendon organ: detect tension, receptor for golgi tendon reflex
o opposite to stretch reflex
o  rate of action potential in Ib fibres
o eg. Golgi tendon reflex
muscle contract-> golgi tendon organ activated-> impulse in Ib sensory neurone-> polysynaptic (spinal
cord) -> reduced impulse in  motor neuron -> muscle relax
 protection of biceps from excessively heavy loads -> muscle relax to drop the load

cardiovascular system
heart: 2 major divisions
pulmonary circulation right side
systemic circulation  left side
location: in the thoracic cavity, left of the median plane (人嘅中軸線), between the *lungs in the
mediastinum* <- (the cavity), between the sternum and vertebral column, above the diaphragm

double-walled sac encloses the heart, consists of two layers

- fibrous pericardium (outer)  tough layer of dense connective tissue
- serous pericardium (inner)  delicate layer that surrounds the heart and has
two layers:
o Parietal pericardium
o Visceral pericardium
- Pericardial cavity between the parietal and visceral pericardium containing
pericardial fluid

3 layers of heart wall

- Epicardium  visceral pericardium, protection against friction of rubbing
adjacent organs
- Myocardium  cardiac muscle layer forming bulk of heart, contraction
- Endocardium  single layer of endothelial cells over layer of connective
tissue, reduce friction by passage of blood through heart

Shape like a pyramid: apex pointing inferiorly towards left hip, quadrilateral base
pointing superiorly towards right shoulder
- Apex: formed by left ventricle, at 5th intercostal space in mid-clavicular line
- Base: posterior surface, formed by both atria (mainly left), pulmonary veins &
vena cava
5 surfaces of heart
- Anterior (sternocostal) surface  R. ventricle
- Posterior (base) surface  L. atrium
- Right Pulmonary surface  R. atrium
- Left Pulmonary surface  L. ventricle (forms the cardiac impression of left
lung)
- Inferior (diaphragmatic) surface  Left & right ventricles
4 boarders (separating surfaces)
- Right border  Right atrium (In line with SVC & IVC)
- Inferior border Left and right ventricle
- Left border Left ventricle (some of the left atrium)
- Superior border Right & left atrium, Great vessels (SVC, Ascending aorta,
Pulmonary trunk (pulmonary artery)
Skeleton
o Dense connective tissue (collagen & elastic fibres)
o 4 fibrous rings (annulus fibrosus)
o 2 fibrous trigones between rings
o 1 membranous part of septum
- anchors heart valve cups
- prevent valves from overly distended
- attachment for cardiac muscles
- electrical insulator between atria &
ventricles (AV bundle is only connection
between cardiac muscle of atria & ventricle)
 - cardiac muscle arranged in spiral / figure-8 bundles pump blood in right
direction & efficiently
- no muscular continuity between aria & ventricle

Atrium
- Pectinate muscle = atrial walls
- Crista terminalis separates pectinate muscle from smooth (posterior) surface
of atria
- Interatrial septum between atria
- Veins to right atrium  systemic circulation, vena cava, coronary sinus

Ventricle
- Trabeculae carneae & papillary muscles = ventricular walls
- Chordae tendineae (heart tendon) anchor atrioventricular (AV) (bicuspid
(mitral) /tricuspid vales) to papillary muscle
- Interventricular septum between ventricles
Great vessels
- Aorta, pulmonary trunk, pulmonary veins, superior & inferior vena cava
External anatomy
- Coronary sulcus: separates atria from ventricles (visually) containing right & left coronary artery
- Interventricular sulcus: separates right & left ventricles containing anterior & posterior (front & back)
interventricular artery
Valves
- Atrioventricular valve: tricuspid (right), bicuspid (mitral) (left)
o **each valve has a set of cups/ leaflets /flaps
- Semilunar valves: pulmonary valve, aortic valve
o 3 half-moon shaped pocket-like structures

left ventricle-> coronary arteries branch off the aorta ->

cardiac muscle -> cardiac veins -> coronary sinus -> right
atrium
coronary heart disease: plague of fatty deposit 
atherosclerosis) -> blood clot (thrombus)
Angina Pectoris: temporary chest pain, pressure or
discomfort, typical distribution at left anterior body
 ischemia 缺血 low blood flow causing angina 心絞痛
Coronary angioplasty (Percutaneous Coronary
Intervention (PCI))  by stent (expanded web)
Coronary artery bypass surgery (replace right
coronary artery by saphenous vein)
Cardiac muscles contract to provide heart automatic rhythmic beat, coordinate contraction of diff chambers of heart

Sino-atrial (SA) node (pacemaker) -> excitation spreads through atrial myocardium ->Atrio-ventricular (AV) node ->
excitation spread down Bundle of His -> right & left branch -> Purkinje fibres distribute excitation through ventricular
myocardium

Sympathetic:  heart rate & force of contraction

Parasympathetic (vagus nerve):  ..
Cardiac centre (hypothalamus) in brain stem detect conc of O2, CO2, pH

Blood vessel except capillaries has 3 layers:

- tunica intima (innermost): single layer of endothelial cell
- tunica media (middle): contain little smooth muscle, many elastic &
collagen fibres
- tunica adventitia (outermost): loose connective tissue
large vessels contain arteries and veins (vasa vasorum) and nerves
**thickness and composition of layers vary with diff vessel types &
diameter

capillaries
wall contains single layer of endothelial cell (endothelium) for exchange of materials
- thoroughfare channels: carry blood from arterioles to venules, blood can pass through rapidly here
- precapillary sphincters: regulate blood flow into capillaries

arteriole end: exit of O2, water, nutrients

by hydrostatic pressure
venous end: entrance CO2, water, waste
by osmotic pressure

**artery dilate & constrict create pulse:

Alternating expansion and recoil of
an arterial wall (always taken in
systemic artery)

**veins store about 65-70% of body’s total blood vol

arteries
- large elastic arteries: thick walled, large diameter, tunica media has little smooth muscle & many elastic fibres
- medium muscular arteries: thick walled, small diameter, tunica media has abundant smooth muscle & some
elastic fibres
- small arterioles: smallest arteries, tunica media has ½ layers of smooth muscle cells & little elastic fibres
o vasoconstriction: O2, CO2,  endothelin,  sympathetic stimulation, vasopressin加壓素, angiotensin
血管緊張素, cold
o vasodilation: CO2, O2,  Nitric oxide,  sympathetic stimulation, histamine release, heat
Systolic pressure  highest arterial pressure (after pumping from left ventricle)
Diastolic pressure  lowest arterial pressure (before entering right atrium)
**Average blood pressure: 120/80 Sphygmomanometer: blood pressure cuff used to measure blood pressure
hypertension
- BP > 140/90
- Essential hypertension (unknown cause)
- Secondary hypertension (known cause: eg. Kidney disease, birth control pills)
- lead to damaged organs and illnesses, e.g. aneurysm, heart failure, stroke, heart attack, cognitive decline
veins
- venule: connect to capillaries, larger diameter than capillaries
- large venules & all veins have all 3 layers
- varicose veins: valves opened

arteriosclerosis: loss of elasticity in aorta, large arteries, coronary arteries

atherosclerosis: deposition of liquid in arterial walls forming plaques
aneurysm: weak spot in blood vessel, ballooning out may rupture
varicose vein: weak, ineffective valves
phlebitis: inflammation of vein -> blood clot forms
thrombosis: blood clot forms in blood vessel
embolism: obstruction of blood vessel by blood clot travelling in bloodstream

pulmonary circuit: right heart to lungs then back to left heart

- pulmonary trunk branches into 2 RIGHT & 2 LEFT pulmonary arteries to both lungs
- 4 pulmonary veins return blood to left atrium
systemic circuit: left heart to body then back to right heart

portal venous system connect 2 capillary beds:

- hepatic portal system: intestine & *spleen* to liver
- **hypophyseal portal system: connect neurons in hypothalamus to endocrine cells in pituitary gland

anastomosis: connection between blood vessels by collateral channels, as alternative pathways when usual routes are
obstructed
- *arteriovenous anastomosis via thoroughfare channel

plasma: 55% of blood content, contains salts, clotting factors, hormones, antibodies, dissolved
gases, nutrients, wastes
- serum: liquid portion of clotted blood without fibrinogen
erythrocytes:
- RBC -> 99% of blood cells
- 2 ways to quantify RBC in blood:
o complete blood count (CBC)
 male: 2.7-6.1 million RBC/mcL female: 4.2-5.4m RBC/mcL
o haematocrit % of RBC in blood
 male: 40-50% female: 38-45% athletes: >50%
polycythemia:
o excess of RBCs in blood (high haematocrit 70-80%)
o  blood viscosity  sluggish circulation, low O2, high blood pressure,  risk of bleeding & thrombotic
disorder
anemia:
o reduction of RBC (low haematocrit <33%)
o inadequate levels of haemoglobin
 thalassemia (abnormal haemoglobin)
  sickle cell
leukocytes:
- WBC:
o Neutrophils: most numerous, phagocytosis, destroy fungal/
bacterial invasion
o Eosinophils: fighting off parasites, infection causing
allergies
o Basophils: least common, release histamine to immediate
inflammation & allergic response
o Lymphocytes: antibody production
o Monocytes: largest, phagocytosis, destroy invaders, antigen
presentation

Leukemia: cancer by with abnormal increase of immature WBC

Platelets:
- Formed in bone marrow from megakaryocytes
- Clot blood by sticking tgt by fibrin
- Haemophilia: bleeder’s disease, lack of clotting factor VIII / IX
Lymph:
- interstitial fluid (tissue fluid)
- significance: provide route of infection/ cancer metastasis
- lymphatic vessel also with all 3 layers
- Lymphatic capillaries → collecting vessels → lymph nodes → lymphatic trunks → lymphatic ducts → systemic
veins (junction between internal jugular vein and subclavian veins)
- Elephantiasis: parasites block lymphatic vessels-> massive swelling, darkening, thickening of skin in affected area

Heart sound auscultation

- 1 st stage “Early diastole” - semilunar valves close; AV valves open, & the whole heart is relaxed
- 2 nd stage “atrial systole” - atrium contracts, blood flow from atrium to ventricle
- 3 rd stage “isovolumic contraction” - ventricles begin to contract; both AV & semilunar valves close, & no
change in volume
- 4 th stage “ventricular ejection” - ventricles are contract & emptying; semilunar valves open
- 5 th stage “isovolumic relaxation” - P↓; no blood enters the ventricles; ventricles stop contracting & begin to
relax, & semilunar valves close
electrocardiogram (EKG/ ECG): recording of electrical activity of heart in a cardiac cycle
- show how fast, steady the heart beats
- P wave − Atria contraction (depolarization)
- QRS complex
o Ventricle contraction (depolarization)
o Atria recovery (repolarization)
- T wave − Ventricle recovery (repolarization)
- PR interval − Atrial systole & AV nodal delay to allow filling of
ventricles
- ST segment − Beginning of ventricle repolarization
Cardiac arrhythmias:
- Normal heart rate: 72 beats/min
- Too fast tachycardia too slow bradycardia
- Caused by disruption of normal electrical conduction system of
heart/ heart disease

Gas exchange
Across alveolocapillary membrane:

- D diffusion constant
- Sol solubility coefficient
- MW molecular weight
- A effective surface area
- T thickness
 ** total area of alveoli in contact with capillary
blood: 50-100 m2
-
surface area (eg alveolar damage 
emphysema, blockade of lung capillaries 
embolism)
  gas diffusion
** distance: thickness of alveolo- capillary
membrane: 0.2- 0.5
-  distance (eg thickened alveolar / capillary
wall  lung fibrosis) ->  gas diffusion
Hemoglobin
- Hb + 4O2
- In healthy adults: 2 alpha chains, 2 beta chais, 4 heme grps
-  ventilation/ blood flow   pressure gradient for gas diffusion
** healthy ppl’s diffusion does not limit gas exchange
o only takes 1/3 capillary length to achieve eqm of O2 between lung and blood for pulmonary gas exchange
in 0.25 sec

tissue gas exchange factors:

- PO2 in capillary blood
- Distance for diffusion
- Tissue properties for diffusion
- VO2 in tissue (tissue O2 consumption)

VO2:
- Fick’s principle: Cin - Cout unit: ml/min
O2 transport in blood matching metabolic needs
- O2 content (200 ml/L) = Dissolved oxygen (3 ml/L)+ oxygen capacity (maximum o2 can be bound to
haemoglobin: 197 ml/ L)
- Oxygen delivery = cardiac output x o2 content
O2 dissociation curve
- Sigmodal: cooperative binding of O2 changes O2 affinity
(allosteric effect)
- Hb saturation % = HbO2  (O2 has been bound to Hb) / O2
capacity x 100%

** factors decrease O2 affinity (its extent/ degree) for uploading O2

in tissue ( rate of Hb saturation %)
-  H+ ions conc
-  PCO2 (Bohr’s effect)
-  To
-  DPG conc
**  PO2  decrease affinity of haemoglobin for H+ ions & CO2
** CO & anaemia decrease O2 content but not Hb saturation!!!

CO2:
- dissolved form: 10%
- bicarbonate ions: 70% (65% in RBC, 5%in plasma)
- Carbamino-compounds: 20% CO2 + HbNH2 ⇌
HbNHCOO- + H+
CO2 dissociation curve
- Effect of PO2 (Haldane effect)
- PO2  favour CO2 carriage   rate of CO2 dissociation curve
Urinary System - Left higher than right as liver occupying space
- Peritoneum membrane in dialysis for filtering

Aorta renal artery segmental artery interlobar artery arcuate artery cortical radiate artery  afferent arteriole 
glomerulus  efferent arteriole peritubular capillaries/ vasa recta cortical radiate vein arcuate vein interlobar
vein renal vein  inferior vena cava

Each kidney contains a million nephrons bounded

together by connective tissue
Nephron = renal corpuscle (glomerulus & Bowman’s
capsule) + renal tubule
- each nephron with 2 capillary beds: glomerulus
+ peritubular capillaries
- cortical nephrons:
o renal corpuscles located in outer
portion of the renal cortex
o Shorter loop of Henle
o Efferent arteriole supplies peritubular
capillaries
o most abundant type of nephrons (~85%)
- Juxtamedullary nephrons:
o Renal corpuscles located deep in cortex
o Longer loop of Henle with vasa recta as blood
supply there
o Efferent arteriole supplies vasa recta

- Renal corpuscle = Glomerulus + Bowman’s capsule

Initial blood filtering component
o Glomerulus: small tuft of capillaries (SA for
filtering), with endothelial cells, mesangial cells
o Bowman's capsule has outer parietal layer &
inner visceral layer
 Cells on the visceral layer: structurally
modified  podocytes

1. Glomerular filtration (ultrafiltration) by high

pressure in glomerular capillaries efferent
arteriole is narrower than the afferent arteriole
- Force favouring filtration: Glomerular
capillary blood pressure (G bp) by
- Force opposing filtration: Fluid (or
hydrostatic) pressure in Bowman’s capsule (BC hp)
Osmotic force due to protein in the glomerulus (i.e.
oncotic pressure / π osm)
- Net filtration pressure = G bp – BC hp - π osm
= pressure responsible for filtrate formation
 afferent arteriole vasodilationblood flow to glomerulus Gp  NFP  Forms glomerular filtrate
efferent arteriole vasoconstriction  capillary blood pressure   NFP  Forms glomerular filtrate
afferent .. vasoconstriction, efferent .. vasodilation vice versa
- Glomerular Filtration Rate (GFR): total amount of filtrate formed by both kidneys per min
determines how well the blood is filtered by the kidneys
o Depends on: NFP, permeability of filtration membrane, SA
for filtration
o Normal GFR: 90-140 ml/min
o Renal clearance: substance not reabsorbed / secreted by
kidney
 determine GFR
 vol of plasma cleared of a specific substance in a given
amount of time
 clearance = excretion amount of a substance / conc of substance in body
 **Renal inulin clearance good to estimate GFR (normal clearance value= 90ml/min)
renal glucose clearance = 0 0 excretion by full reabsorption
 creatinine rough estimated GFR (eGFR)
 Levels are affected by age, gender, food intake, muscle mass;
Freely filtered + undergoes a small amount of secretion in kidney
-->slightly overestimated GFR
o Renal corpuscle filtration barrier:
 Fenestrated endothelium (50-100nm long fenestrae) of glomerular capillary
 fused basal lamina of endothelial cells and podocytes
 filtration slits of the podocytes
podocytes’ feet interdigitate with each other to form filtration slits of 20- 30 nm wide

o find molecules by 'sieving' mechanism by size

and charge (-ve charge of the basement membrane
repels -ve charge proteins eg. Albumin)
only permits passage of water, ions, and small
molecules, but not large size proteins, from the
bloodstream into the Bowman’s capsule

o Proteinuria (albuminuria/ urine albumin): sign

of chronic kidney disease, result from diabetes,
hypertension, diseases that cause inflammation in
kidneys fusion or collapse of podocyte foot
process, splitting of the glomerular basement
membrane (GBM) leak other molecules eg RBC,
large protein
 Warning > 150mg/24hr or 1omg/ 100ml
 Proteinuria > 3.5 g/24 hours  nephrotic syndrome
2. Tubular reabsorption by renal tubules
o proximal tubule

 Longest section of nephron

 With cuboidal epithelial cells with microvilli  maximise spaces
available for reabsorption
 70% of the filtrate reabsorbed  major site for reabsorption
 production of calcitriol (active hormonal form of vitamin D, help Ca2+
absorption in intestine) under control of parathyroid hormone
chronic kidney disease gradual loss of kidney function
- headaches, ability to concentrate urine, oliguria,serum creatinine, edema, GFR progressively decrease, mild
anemia,  serum K,  BP, Weakness & fatigue
  transcellular route: primary active transport,
secondary active transport, facilitated diffusion,
osmosis
 paracellular route: diffusion of urea, Ca2+, K+

 transport maximum (Tm): substances

reabsorbed via transporters (mainly active
transport) exists maximum rate for their
transport all available carriers are occupied
with substrate

 Glycosuria in diabetes mellitus: all glucose

transporters are saturated glucose amount in
filtrate exceed transport of maximum of proximal
tubule urine becomes more abundant containing
glucose
 Male Tm of glucose: 375mg/min female: 300mg/min
o Loop of Henle
 Connect proximal tubules to distal tubules
 Located exclusively in medulla
 descendent & ascending portions, consisted of
simple squamous cells
 build up high conc of Na+, Cl- in interstitial places, tissue of medulla as driving force in further
conc of urine by at collecting ducts
 salts & water reabsorption: countercurrent multiplier system
o distal tubules
 shortest segment in nephron (5mm in human)
 cuboidal cells without microvilli
 at renal cortex
 regulate flow in glomerulus & nephron by producing renin
 reabsorption & secretion of electrolytes
 Has unique capacity to adapt to changes in hormonal stimuli, mainly
aldosterone (stimulates Na+ reabsorption), parathyroid hormone (stimulates Ca2+ reabsorption)
 straight portion of distal tubule contacts glomerulus  forming macula densa (closely packed
specialized cells that can sense Na+ conc in filtrate)

o collecting duct
 cortical, medullary portions
 2 types of cells: principal cell (PC) for water reabsorption, response to Vp; intercalated cells (IC)
for acid-base balance (acid base transport), has unique capacity to adapt to changes in hormonal
stimuli, mainly vasopressin (anti-diuretic hormone (ADH) which stimulate water reabsorption
from filtrate)
 both cuboidal shape

 Production of dilute urine in collecting duct is accomplished by simply allowing filtrate from
Loop of Henle to pass on to renal pelvis
Overhydration (Plasma hypo-osmolality) No vasopressin (or antidiuretic hormone [ADH])
stimulation No water reabsorption from lumen Large vol of diluted urine
 Formation of concentrated urine in collecting ducts occurs in response to the insertion of water
channel, aquaporin 2 (AQP2), onto the apical membrane of collecting duct cells  making them
permeable to water small amount of concentrated urine
Dehydration (Plasma hyperosmolality) Vasopressin release from the posterior pituitaryAQP2
insertion onto the apical membrane of principal cells Water reabsorption from the lumen due to
the hyperosmotic environment created by the loop of Henle Small vol of concentrated urine
 3. Tubular secretion
Acid base balance
- Always net addition of acid to body after any typical diet, respiration
- pH narrow range within 7.38-7.42 for functioning enzyme
- amount of acid excreted per day must equal to the amount produced per day
- regulated by chemical buffering agents: one or two molecules binds H+ when the pH drops/ releases H+ when the
pH rises
- carbonic acid-bicarbonate buffer system is the main buffer of the extracellular fluid
o carbonic acid & sodium bicarbonate (HCO3 - )
- Even though chemical buffer system can inactivate excess acids and bases momentarily, they are unable to
eliminate them from the body
 Lungs and Kidneys to eliminate acid in the body
- Renal system (compared to lung): only system getting rid of non-volatile acids eg uric acid, lactic acid, ketone
bodies (excretion oh H+), regulate alkaline substance in blood (excretion of HCO3-), restore chemical buffers for
managing H+ level in extracellular fluids (reabsorption of HCO3- from
filtrate & generation of HCO3- from glutamine) main acid base
regulatory organ
- Proximal tubules:
o 80% of filtered HCO3- reabsorbed by proximal tubules, rest
reabsorbed by distal nephron
o **reabsorption of filtered HCO3- always accompanied by
secretion of H+ and vice versa
o HCO3 - reabsorption in proximal tubules is achieved by
Na+/HCO3- cotransporter on basolateral membrane
o H+ secretion into lumen of proximal tubules is achieved by two
transporters expressed on apical membrane: Na+/H+ exchanger
(NHE) & H+ -ATPase

o Carbonic anhydrase (CA) plays an important role in H+ secretion & HCO3 - reabsorption in proximal
tubules  enzyme that catalyze rapid interconversion of carbon dioxide & water to bicarbonate (HCO3-)
& protons (or vice versa)
o Intracellular CA (CA-II) facilitates generation of H+ and HCO3-
o membrane-bound CA (CA-IV) facilitates production of H2O and CO2 from carbonic acid

o Generation of novel bicarbonate molecule is achieved by process of

ammonium (NH4+) synthesis (ammoniagenesis), which occurs only in
proximal tubular cells:
Glutamine  2 HCO3- (to interstitial) + 2 NH4+ (to filtrate)
o 2 suptypes of IC:
 type A (IC-A): secret H+ & NH3  luminal expression of both H+ ATPase & H+/K+ ATPase;
Expresses anion-exchanger AE1 on the basolateral membrane
 Type B (IC-B): Secretes HCO3-  luminal
expression of Cl-/HCO3- exchanger
(transporter for Cl-; HCO3- excretion), called
pendrin
Expresses only H+ ATPase on the basolateral
membrane
 o **Chloride ion depletion results in hypochloremia hence decreasing chloride delivery to pendrin ->
impairment in the excretion of HCO3- (i.e. alkalosis high pH in body fluids)
o Efficient H+ secretion depends on concomitant secretion of ammonia (NH3) from type A IC, which is
subsequently protonated in lumen to ammonium (NH4 +)
o NH3 freely diffuse across the apical membrane /
secreted via the Rhesus glycoprotein (Rhcg) ammonia-specific transporters
o Luminal NH3 titrates luminal H+, forming NH4+  maintaining low luminal NH3 conc necessary for
further NH3 secretion

- Respiratory acidosis (low pH in body fluids) caused by hypoventilation (airway obstuction)

- Respiratory alkalosis caused by hyperventilation
- Metabolic acidosis/ alkalosis caused by abnormal renal function
o Acidosis: Excessive accumulation of non-volatile acid as primary reduction in serum bicarbonate conc in
body, low plasma pH
Diabetes mellitus-induced ketoacidosis, Hypoxia- / sepsis-induced lactic acidosis, Severe diarrhea
(loss of HCO3-) from the GI tract, Renal failure, Hyperkalemia
 Symptom: headache, rapid & shallow breathing (compensatory hyperventilation), fatigue,  heart
rate, osteoporosis, fruity smells when breathing (for diabetes-induced ketoacidosis)
 Academia coma & death
o Alkalosis: high plasma HCO3- level
 Caused by 2 processes: generation of metabolic alkalosis, maintenance of metabolic alkalosis
 kidney failure, prolonged vomiting loss of H+ from stomach, hyperaldosteronism-induced
hypokalemia, hypochloremia
 Symptoms not specific **hypokalemia: headache, compensatory hyperventilation, arrhythmias,
muscle weakness

** compensatory response eg metabolic disorder compensated by lungs & vice versa

Gastrointestinal system

Ingestion **propulsion (from oesophagus, movement of food along canal (swallowing at oral pharynx & peristalsis till
large intestine) mechanical digestion (**segmentation in small intestine!!) chemical digestion absorption
defecation

Neural control in GI tract

- Parasympathetic nervous system (PNS) stimulates digestion; sympathetic (SNS) inhibits digestion

o Saliva:
 99.5% water, cleanses mouth, moisten
& dissolve food, aids formation of bolus
 lysozymes providing anti-bacterial
protection
 amylase digesting starch
 lingual lipase (from von Ebner’s
glands of tongue) digesting lipid

 salivation mediated by neural reflexes

upon presence of food in mouth, thought
of food
 PNS stimulates large vol of
watery saliva rich in enzymes
 SNS stimulates small vol of thick
saliva rich in mucus
**Mouth becomes dry when we are under stress
o Swallowing (deglutition)------>

o Peristalsis
 Circular muscle
**contract & constricting
passageway, pushing
bolus down towards
gastroesophageal
sphincter
 Longitudinal muscle
**contract, shortening
passageway ahead bolus

o Stomach: gastric secretions

 Chief peptic cells: inactive pepsinogen,

gastric lipase
 Parietal (oxyntic) cell: HCl activating
pepsinogen to pepsin, intrinsic factor (required for
vitamin B12 absorption)
 G cells: gastrin (hormone stimulating
parietal & chief cells)
 Mucous cells: mucus (protect stomach wall
against pepsin & acid)
 3 phases:
1. cephalic phase (minutes): prepare stomach for
arrival of food
neural (vagus nerve) stimulation  secret
gastric juice
2. gastric phase (3 hrs): homogenize & acidify
chime, initiate protein degestion by pepsin
 neural (short reflex, vagus nerve) + hormonal
stimulation gastric juice secretion, gastric
mobility
3. intestinal phase (hrs): control rate of chime entry
into duodenum
 neural (short reflexes, vagus nerve) +
hormonal (cholecystokinin, secretin, GIP
released by intestine)  gastric juice secretion,
gastric mobility

o pancreas
 endocrine: insulin, glucagon
 exocrine: secret pancreatic juice: with bicarbonate HCO3- neutralising gastric acid, optimum pH
for pancreatic enzyme functioning in small
intestine, active enzymes (amylase, lipase,
nucleases), inactive (trypsinogen,
chymotrypsinogen) **nogen= inactive**

 chyme stimulate duodenum to release

hormones into blood:
 secretinstimulate pancreas secreting HCO3-
rich juice
 cholecystokinin  stimulate pancreas
secreting enzyme rich into blood
 activation of vagus nerve  stimulate
pancreas secretion
 o gallbladder (green, muscular sac, thin walled) store & **concentrate** bile by absorbing water during
inter-digestive period
 release bile from gallbladder to bile duct through **cystic duct**
 bile salts absorbed in ileum & recycle by liver via enterohepatic circulation (hepatic portal
vein)
 Pancreatic lipases digest triglycerides on surface of lipid droplets, releasing fatty
acids & monoglycerides (which form micelles).
 chyme stimulate duodenum to release hormones into blood:
 secretin (& bile salt transported from blood) stimulate liver producing bile
 cholecystokinin  stimulate gallbladder contract, hepatopancreatic sphincter relax
 activation of vagus nerve  gallbladder contract
- small intestine for segmentation (mechanical digestion churning & fragmentation of food substance, making it
mixture) & producing intestinal juice
 goblet cells secreting mucus
 Brunner’s glands in duodenum secreting thick alkaline mucus protect
duodenum from acidic chime, optimal pH for intestinal enzymes
 Intestinal crypt cells secret intestinal juice (clear to pale yellow, watery
secretion with small amount of digestive & anti-bacterial enzymes)

 Brush border enzymes at apical membrane of absorptive cells lining small

intestines**essential for complete digestion Amylase cannot break down
starch to glucose monomers; Trypsin & chymotrypsin cannot break
down protein into amino acids

 Second active transport across apical membrane

 Facilitated diffusion across basolateral membrane

 Fat soluble vitamins (A D E K) absorption similar to fat (Taken

up by micelles transported into enterocytes by diffusion
packaged into chylomicrons to enter lacteals)
 Water soluble vitamins (B C) absorbed by diffusion/
active transport
 **Vitamin B12 requires intrinsic factor (secreted by
stomach) for absorption
 - large intestine
o colon for last water absorption 20% ard 1L
 faeces become compacted
o rectum, anus: faeces storage & defecation

Gut Flora
- no of cell in human body: 1013 10 trillion
- .. of micro-organism in human gut: 1014 with >500
species
o in colon: 1010 - 1012 CFU/ml
- function: control pathogens, synthesize vitamin B, K,
enzymes, neurotransmitters, regulate metabolism,
regulate immune system, inflammation

Hormonal control
> 50 hormones in human regulate mood, sleep cycle, growth and development, metabolism and energy balance, body
defence, reproductive processes, homeostasis

endocrine signalling through bloodstream

paracrine act on next cells
autocrine at on self
exocrine glands to ducts/ channels
classification of hormones:
- amino acid derivatives: derived from chemical
modification of amino acid (tyrosine, tryptophan
into thyroid hormones), half-life in blood varies
from mins to days
- peptide & protein hormones: chains of amino acid
(eg insulin), synthesized in rough ER as precursor
before undergoing further post-translational
processing into active hormone, store in vesicles in
large amount before released, short half-life in
blood (mins)
- steroid hormones: derived from cholesterol/ cortisol, bind to carrier
protein (albumins, globulins) when travelling, synthesized in smooth ER on
demand, longer half-life (hours)
hormone  specific target cell with specific receptor

- water-soluble hormones: peptide & protein hormones, repelled by lipids in

cell membrane, bind to receptor protein on plasma membrane, binding of
hormone to receptor initiates series of events generation of second
messengers within cell
1. G-protein-coupled receptors (GRCR; 7-transmembrane (TM)-spanning
receptors) (eg receptor for PACAP, glucagon, oxytocin, vasopressin)
respond to ligands by undergoing dynamic conformational changes in
TM domain alter their ability to communicate with intracellular
signalling partners
2. Change conformationActivation of associated G protein by
exchanging GDP bound to G protein for GTP
3. Intracellular signalling pathways G G being activateddepends on G subunit type
 Gs: stimulation leading to increase in cAMP
 Gi: .. decrease cAMP
 Gq: .. activation of phospholipase C (PLC)
o Eg vasopressin receptor V2R: binding vasopressin (Vp; anti-diuretic hormone) at extracellular interface
triggers conformation change in transmembrane domain 6 & intracellular loop Gs stimulation,
enzyme activation change water permeability of collecting tubule cells by insertion of water channel
AQP2
---> **hormone affect physiology of target tissue by inducing protein expression/ change membrane
permeability
 o Enzyme-lined receptor: ligand binding receptor dimerized  conformation change
transmitted via transmembrane region activates enzymatic activity  signalling
cascades
** cytoplasmic domain of this receptor either has an intrinsic enzyme activity or
associates directly with an enzyme, including tyrosine kinase, tyrosine phosphatases,
serine/threonine protein kinase
***requires many intracellular signalling steps changes in cell proliferation,
differentiation, survival, migration, etc  disorders in fundamental events-> cancer
o Insulin receptor: member of tyrosine kinase family of transmembrane signalling
protein, with subunit for binding on membrane surface; &  subunit as protein kinase
catalysing
phosphorylation of proteins inside cell
Binding of insulin onto α-subunit of insulin receptor causes phosphorylation of β-
subunit (autophosphorylation)  docking centre for recruitment of diff substrate
adaptors (eg insulin receptor substrate 1 (IRS-1)  activation of other enzymes that
mediate insulin effects at last)

 2 main pathways of insulin signalling: PI3K/AKT pathway (mostly controlling metabolic effects of
insulin); Ras/ERK pathway (controlling cell growth/ differentiation induced by insulin)
**hormones can act via control of intracellular enzyme activity

- lipid soluble hormones: steroid hormones, diffuse through membrane, bind to receptor protein inside cell
1. binding of steroid hormones to receptor  dissociation of repressor protein
2. hormone-receptor complex translocated to nucleus
3. hormone-receptor complex form dimer
4. dimerized complex act as transcription factor, binding to hormone response element (HRE) on target gene
inducing & supressing gene expression
**steroid receptors as transcription factor containing a site for DNA binding & transcriptional activation
o eg (o)estrogen receptor (ER) binding cytosolic ER enters nucleus recruit specific transcriptional
coregulatory protein binds to estrogen-response element (ERE) in promoter region of estrogen-
responsive genes
**receptor binds to hormone receptor change conformation interact productively with other
components of the cell alternation in physiological state of cell at last

complicated hormonal response

- many steps after initial hormone binding to receptor many places can undergo regulation
- hormonal signal amplified along cascade
- for target cells to integrate info it receives from diff stimulus specific response elicited in given cell is
determined by the cell rather than the hormone
one hormone can bind to multiple receptors diff action, potency/ binding affinity
- Vp + V1a receptor vasoconstriction (via Gq signalling pathway)
- Vp + V1b receptor corticotrophin secretin (Gq)
- Vp + V2 receptor  renal water reabsorption (Gs)
One receptor can bind multiple hormones
- Oxytocin receptor with oxytocin, Vp
Maintain internal environment upon exposure of external environment
- Redundant effect: diff hormones produce same effect, safe-guard mechanism for important physiological function,
(eg epinephrine, glucagon, cortisol acting on liver to increase blood glucose level) **not identical hormones,
functioning with diff time constant!!
Produce synergistic outcome: combine action of redundant hormones to produce greater effects than sum of
individual effects
** Glucagon, epinephrine, and cortisol interact synergistically during prolonged fasting  rapidly restore normal
blood glucose level
- Reinforcement effect:
o same hormone acts in diff tissue  diff response that reinforce each other
(eg cortisol: accelerate breakdown of proteins into amino acids in muscle increase amino acid supply to
liver; breakdown of fat in adipose tissue  increase glycerol supply to liver; stimulate production of
glucose from amino acid & glycerol in liver; decrease body sensitivity to insulin  overall effect  blood
glucose level
o same hormone diff response in single cell reinforce each other for overall effect
 (eg aldosterone (at molecular level): binding to mineralocorticoid receptor (MR) in distal tubule cell
different gene expression
 Na+/K+ APTase expression on basolateral membrane
 Na+ channel (ENaC) expression on apical membrane
 K+ channel (ROMK) expression on apical membrane
Overall effect: Na+ reabsorption, K+ excretion
o Antagonistic effects: hormone act to return body condition within acceptable limits from opposite extreme
(ie **one hormone opposed action of another dual control more precise regulation than negative
feedback!!)
(eg insulin vs glucagon on blood glucose level)
- Permissive effects: presence of a hormone at certain conc enhance responsiveness of one target organ to the second
hormone (ie one hormone control expression of receptor of another hormone)
(eg oestrogen induce expression of progesterone receptor in uterus during proliferative phase
 oestrogen induce proliferation of uterine endometrium (ie increase thickness of uterine wall)
 progesterone induce development of uterine endometrium, including blood vessel formation 
prepare for implantation
rhythms of hormone secretion
- hormone conc in blood plasma always fluctuates in mins, vary widely in normal individual over course of a day,
**3 rhythms
o pulsatile secretion: most hormones
released in short burst, regulated by
physiological stimuli eg nutritional
factors. (eg insulin, GnRH)
o diurnal secretion: eg cortisol vs
melatonin
cortisol peaking shortly after waking,
melatonin peaks at night tell the
time to body cells
o cyclic secretion: hormone secreted in
complicated cycle with respect to
bodily events (eg menstrual cycle)
cyclic change in hormonal levels
control & orchestrate the events of menstrual cycle

hormonal secretion regulation: 3 types!!

- Control by humoral stimuli control of hormone release in response to changes in extracellular fluids/ blood-
borne chemicals
o Eg parathyroid hormone (PTH) secretion in response to Ca2+ level
High Ca2+ in extracellular fluid  X PTH secretion low PTH secretion
o Insulin secretion in response to high blood glucose level
 In unstimulated state, pancreatic  cell ATP-sensitive potassium channels are open, keeping
resting membrane potential ~ -60 mV
 In presence of high extracellular glucose level
1. Glucose entre cell by diffusion through membrane transporter
2. ATP production
3. Closure of ATP-sensitive potassium channels X
K+ efflux
4. Depolarisation
5. Voltage-dependent Ca2+ channel open  increase
cytosolic Ca2+ conc
6. Insulin release
- Neural stimuli: nervous system directly stimulates endocrine glands
o Norepinephrine/ epinephrine secretion from adrenal medulla in response to
stress-induced activation of sympathetic nervous system
 - Hormonal stimuli: hormone secreted stimulate secretion of another hormone
o Hormones from hypothalamus & anterior pituitary

Hormone secretion & serum hormone conc maintained by feedbacks

- Positive feedback (closed loop): reinforce (increase) changes in controlled condition
Eg oxytocin secretion during childbirth causing contraction of uterine muscle
① Uterus contract to push baby out
② Nerve impulse send to hypothalamo-pituitary axis
③ Oxytocin release at posterior pituitary
④ Uterus responds to oxytocin by contracting more vigorously
⑤ After birth, uterus contraction lessens and positive feedback cycle is broken
- Negative feedback (closed loop): hormone secretion inhibit further hormone secretion of secretory cell
Eg glucose production by glucagon
1. Fall in blood glucose level stimulates  cells of islet of Langerhans to release glucagon
2. Glucagon  blood glucose level
3. Restore blood glucose conc, glucagon secretion 
o complex of multi-level!! 3 sub categories of negative
feedback!!
 a= Long loop, b= short loop, c= ultra-short
loop

 Greater degree of fine tuning of hormone secretion, minimize changes in hormone secretion in
event that one component of system is not functioning normally
Eg thyroid hormone secretion
1. Thyroid releasing hormone (TRH) stimulate anterior pituitary secreting thyroid-stimulating
hormones (TSH)
2. TSH stimulate thyroid glands producing thyroid hormones
3. Too much thyroid hormones, TRH/TSH secreting cells inhibited
o Closed loop negative feedback maintains conditions at constancy near pre-determined set-point
(homeostatic eqm), which can temporary adjusted by changing demands from body
Eg epinephrine override predetermined set pt of blood glucose level in
both negative feedback systems operated by insulin & glucagon by
inhibiting insulin secretion & stimulating glucagon secretion
**set pt can be changed/ overridden; set pt deviation from constancy is
mainly achieved by intervention of additional signal outside the
negative feedback system
- Feed-forward control (open loop): anticipatory預料的 response in later stage of
pathways which can be positive/ negative
Eg cephalic insulin response to meal ingestion
3 ways regulating hormone activity
- Conversion of hormone to its active form
o Some hormones secreted as prohormone must be activated through series of activation steps
Eg conversion of angiotensinogen to angiotensin ii within circulation
Conversion of inactive thyroid hormone T4 to active T3 within target cells

- Regulation of hormone receptors

o hormone receptor interactions are saturable (limited, finite no of binding sites)
o more receptor available, more likely can respond (biological effect is proportional to amount of complex
that forms)
 priming effect (receptor up-regulation): hormone
induce more its own receptor expression in target cell
eg high frewuency GnRH pulse  increase sensitivity of its
target cell (anterior pituitary cells) (increasing no of receptors)
 desensitization (receptor down- regulation): occurs
after long exposure to high levels of hormone, internalisation
of receptor-hormone complex used to reduce no of cell-surface
receptors  sensitivity
eg gorth hormone downregulates own receptors by targeting
the receptor to degradation via internalization decrease
sensitivity

o hormone clearance: hormone signals must be turned off when they have served their purpose prevent
prolonged exposure to target cells to hormone; a process of lowering hormone level in blood through:
 degradation by enzymes in liver & excretion into bile: nature of specific structural modification
involved in hormone degradation differs for each hormone class
 peptide hormones: proteolysis; steroid hormones: reduction, hydroxylation, oxidation,
decarboxylation, esterification
 degradation by enzymes in kidney & excrete in urine
 removal by enzymatic processes inside target cell via internalisation of hormone-receptor complex
followed by lysosomal degradation of hormone
endocrine disorder
- hyper= too much
- hypo= too little
causes:
problems in secreting glands eg tumour, infection (1o disorder)
problem in endocrine feedback system, hypothalamic-pituitary axis (2o disorder)
auto-immune disorder (type 1 diabetes mellitus, grave disease)
genetic disorder (Kallmann syndrome, cretinism)
Immune system
Complex network of lymphoid organs (bone marrow; thymus; lymph nodes; spleen; tonsils; lymphocyte collections in
lining of intestinal, respiratory, genital, urinary tracts), cells, humoral factors, cytokines
Blood leukocytes (WBC) with plasma protein detect & eliminate microorganism

Neutrophils 40-75%
- granules of neutrophils contain variety of enzymes (eg myeloperoxidase producing hypochlorous acid HOCl from
hydrogen peroxide H2O2
- peripheral blood neutrophils equally distributed into circulating pool & marinating pool lying along endothelium of
blood vessels
- response to stimuli neutrophils released into circulating pool
monocytes 4-10%
- produced at bone marrow release to bloodstream
- circulating for 20-40hrs migrate into tissue  develop macrophages Both phagocyte for primary defense
- macrophages act as antigen-presenting cells to T cells
- Chemotaxis (cell
eosinophils 1-6%
- allergic response, defend parasitic infection (eg C.elegans)
basophils 0-2%
- specific kinds of inflammatory reaction, prevent blood clotting too quickly
- contain vasodilator histamine promote blood flow to tissue
lymphocytes 16-45%
} mobilization & migration):
phagocytes attracted to
site of infection by
chemotactic substance
released from damaged
tissues
- T cells: cell-mediated immune defence responding to cells that display major - Phagocytosis
histocompatibility complex (MHC) markers binding with antigen-presenting - Killing & digestion: occurs
cell by oxygen-dependent
o Cytotoxic T cells destroy (by inducing apoptosis) cells with MHC-I pathways (superoxide 02-,
o Helper T cells stimulate B cells to produce specific antibody & H2O2 &); oxygen-
stimulate non-specific agent (NK & macrophages) to destroy antigens independent (lysozyme)
on MHC-II
- B cells: membrane-bound form of antibody on surface of cells
o Activated transform into plasma cells synthesizing & secret antibody
o Can also be antigen presenting cells (APC)
- Natural killer cells destroy tumour cells & virus infected cells

** specific antigen recognition!!!

** diversity: ~1018 kinds of antigen receptor configuration as one
receptor for each diff antigens might be encountered
**Memory

2 types of immunity: innate immunity (non-specific); adaptive immunity

(specific)
inflammation Response in vascular tissue
- Stimuli (infection, damage…)→ Mediators (chemokine, cytokine…)→ Inflammation
- Eg TNF-α is a macrophage-derived cytokine that induces many inflammatory reactions: fever, production of
cytokines, endothelial gene regulation, chemotaxis, leukocyte
adherence…
Antibody structure
- Immunoglobulins
- Produced in response to foreign molecules in body
- One or more copies of Y shaped unit, 4 polypeptide chains; each Y
contains 2 identical copies of light chain; top of Y shape contains
variable region as antigen binding sites

Classification of antibodies
In mammals antibodies into 5 classes based on no of Y
units and type of heavy chain

- IgG: most common, increase production after

vaccination; monomer easy to produce
- IgA: mainly in secretion fluids (eg mother milk)
- IgE: responsible for allergic reactions
- IgM: secreted during primary immune response; more Y units for faster easier detection
- IgD: unclear function

RBC cell antigens

- ABO (first important) & Rh (second important) major blood grp
- Red cell antigen incompatible with plasma antibodies fatal reactions eg agglutination (clotting), capillary
blockage, kidney failure)
Rh blood grp system:
o IgG anti-RhD antibodies in RhD-individuals may develop after exposure to RhD+ red blood cells following
blood transfusion/ during pregnancy

Expression/ purification by gel electrophoresis  crystallisation x ray diffraction  structure determination

clinical problems associated with immune functions

- Overactive/inappropriate immune response
o  allergy (hypersensitivity reactions)
 delayed hypersensitivity inflammation due to interplay of T cells & macrophages
 immune complex hypersensitivity  complement activation by antigen-antibody complexes
 immediate hypersensitivity: antigen binds to IgE antibodies which are bounded to mast cells
mast cells release inflammatory mediators eg histamine  produce allergic symptoms
o autoimmune disease
 eg rheumatoid arthritis (RA): chronic inflammation in RA supported by induction of
autoimmunity, overproduction of pro-inflammatory cytokines (TNF-)
 Sirt6 TNF- RA
- underactive
o immunodeficiency eg acquired immunodeficiency syndrome (AIDS)
 AIDS caused by human immunodeficiency virus HIV target helper T CD4 cells
 Bind to surface of CD4 cellsenter CD4 cells becoming part of cells
 CD4 cells multiply to fight infection also multiply copies of HIV
 Continue replicating HIV  gradual decline of cd4 cell
o higher risk developing infections & cancers
- undesirable
o graft rejections
 rejection of tissue transplant initiated by Human leukocyte antigen (HLA) (human version of
MHC) proteins on transplanted cells; mainly by cytotoxic T cells
o transfusion reactions
 mediated by antibodies: transfused erythrocytes being destroyed if recipients has natural
antibodies against antigen on red cells