Ben Blood Physiology Medics Week 1

Blood Physiology
Ben Bhunu, Ph.D Biomed.

Email: [email protected], Cell: 0777036137/ +15045965507
Lecture 1: Introduction
Study Objectives
• Describe fluid distribution in the body i.e. TBW, ICF, ECF, ISF, Plasma.
• State the normal values of blood and plasma volume.
• Discuss the various functions of blood.
• State the components of blood, Cellular, and plasma.
• Describe the process of hematopoiesis, state sites of formation at different
stages.
• Define hematocrit (packed cell volume) and describe how it is measured. What
are the differences in hematocrit in males and females.
• Describe the composition of plasma.
• List the types of plasma proteins and normal plasma protein concentration.
• Describe the functions of plasma proteins.
• Outline the different causes of a low protein concentration and the possible
consequences of a low protein concentration.
Body Fluid Composition
• Human life is dependent on water.
• Humans are 75% H2O by mass at
infancy and 50-60% water in
adulthood.
• Fluid distribution in the body is
divided into two: (a) Intracellular
Fluid (ICF) (b) Extracellular Fluid
(ECF).
• ICF also known as cell cytoplasm
constitutes 40% of total body weight
(TBW).
• ECF constitutes 20 % of total body
weight and is divided into (a) plasma
5% of TBW and Interstitial fluid 12%
of TBW.
Blood composition
• Amount of blood varies according to
weight and size: 70 kg man has 5-6 L of
blood.
• Blood is divided into two component: (a)
Plasma consist of 55% (b) Cellular
components consist 45%
• Plasma is made up of 99% water and 1%
comprises of dissolved solutes such as
protein, electrolytes, vitamins and
nutrients.
• Cellular components consist of white
blood cells, platelets and red blood cells.
Cellular Components of Blood
• Granulocytes AKA polymorphonuclear

leukocytes due to the shape of their
nucleus.
• Neutrophils have neutral staining
nucleus
• Eosinophils stain with eosin dye
• Basophil
• Lymphocytes are regulatory and
antibody producing cells
• Monocytes have no granules and are
phagocytic
Functions of Blood
• Basically, fall into 3 main categories (a)

Transportation (b) Regulation (C)
Protection
• Transport: gaseous exchange, nutrients,
hormones, waste products.
• Regulation: temperature homeostasis,
acid-base balance.
• Protection: carry immune cells, cytokines
(chemical messengers), Hormones,
Clotting factors,
Hematopoiesis
• The process that governs maturation,
development and formation of blood.
• Take place in the hematopoiesis system
(liver, spleen and bone marrow)
• The process starts with a single,
pluripotent hematopoietic stem cell.
This cell can virtually divide into any
cell of the blood lineage and bone
marrow stem cell.
• Lineage specific commitment occurs
after activation of specific
transcriptional programs with the cell
in response to specific cytokines and
growth factors
Plasma
• Constitutes the watery part of blood and appears light- yellow in color.
• Serum is simply plasma without fibrinogen.
• Plasma constitutes 92% water and 8& solids.
• Plasma solids includes (1) Coagulants, mainly fibrinogen, for clotting (2)
plasma proteins, mainly globulin and albumin, which maintain colloidal
osmotic pressure, (3) electrolytes like Na+ , K+, Cl-, Ca2+, Mg2+, HCO3 to
maintain blood pH, (4) Immunoglobulins to help fight infections (5)
Enzymes, hormones and vitamins.
Plasma Protein and their concentration in blood
Functions of Plasma Proteins
• Clotting Factors: Play an essential role in blood clotting.
• Examples: Fibrinogen, Prothrombin, tissue thromboplastin/ tissue factor, ionized

calcium, labile factor (Proaccelerin) Stable factor (proconvertin and
antihemophilic factor.
• Activated by damage to the endothelium and blood exposure to collagen.
• Collagen is normally found beneath the endothelium of blood vessels.
• Deficiency in clotting factors results in conditions like hemophilia and Von

Willebrand disease. These conditions are characterized by excessive bleeding
from minor injuries often resulting in internal bleeding.
• Albumin: main protein that controls oncotic pressure and is a transporter

of multiple endogenous and exogenous substances in the body. Infusion
of albumin is used in hemorrhagic shock, burns, and cirrhotic patients.
• Globulins: Group of blood proteins with a globular structure. Divided into

alpha, beta and gamma globulins: Much bigger than albumins. Produced
by the liver, responsible for maintaining oncotic pressure and have carrier
function in the blood.
• Immunoglobins: These protein play a key role in the defense against

bacteria, fungi and viruses.
• Have five classes, classified based on their roles and structure: These
classes are, Immunoglobulin A, D, E, G and M:
• Disorders in the production of immunoglobulins as in congenital and

primary immune deficiency occur when the body cannot synthesize
antibodies.
• Key in the manufacture of vaccines.

• Enzymes: Alpha antitrypsin is produced by the liver and breaks down

proteins produced during inflammatory processes in the lungs.
• Other enzymes may be tissue specific and also found in blood as

biomarkers of tissue specific diseases, eg cardiac, liver and kidney.
• Hormones: angiotensin, testosterone ,estrogen, progesterone,

aldosterone, vasopressin etc.
Causes of Low Protein Concentration
• Blood proteins are maintained during starvation and are only depleted
under severe starvation.
• Malabsorption of proteins may leads to low plasma protein

concentrations.
• Liver diseases and renal insufficiency may results in low plasma

concentration.
Examples of Disease with Low Plasma Protein Concentrations
• Thrombotic thrombocytopenic purpura (TPP). Type of hemolytic anemia

which manifest as fever, thrombocytopenia, hemolytic anemia and renal
dysfunction. Caused by deficiency or inhibition of ADAMTS13 protein
which is a metalloproteinase that breaks down big von Willebrand factor
multimers (vWF).
• The unbroken vWF multimers cause increased platelet adhesion and

thrombosis.
• Clotting disorders: Hemophilia A and B
• Hemophilia A is due to deficiency of factor VIII
• Hemophilia B is due to deficiency in factor IX
• Symptoms involved hemarthrosis (bleeding in joints) and hematomas

(blood clots in the tissue)
• Immunodeficiency: Bruton disease (agammaglobulinemia) : Failure to

produce immunoglobulins: pre B cells fail to mature into B cells which can
produce antibodies.
• Edema (low plasma protein) : Decreased plasma oncotic pressure results

in capillaries leaking fluid and build of fluid in peripheral tissues.
Lecture 2: Red Blood Cells
Lecture 2
Study Objectives
• State the normal values for Hemoglobin concentration red cell count, red cell life span, red cell
• volume, mean corpuscular hemoglobin.
• Describe the structure of Hemoglobin and its role in O2 transport.
• Discuss how red cells are manufactured and destroyed Jaundice, (types)
• Describe the role of Iron, Vitamin B12 and Folate in the synthesis of Red Blood Cells. How is Iron,
• Folate and Vitamin B12 handled by the human body. (Sources, absorption, storage, excretion) and
• other hormones (androgens, Thyroid, cortisol, Growth Hormone.
• Explain how nutritional deficiencies lead to anemia.
• Discuss the Regulation Red Blood Cell Synthesis. The Role of Erythropoietin (site of synthesis, stimuli
increasing its secretion) and other hormones (androgens, thyroid, cortisol, growth hormone).
• The effects and causes of a low RBC count (anemia) and high RCC (polycythemia).
• Summarize the key features of iron deficiency, megaloblastic and sickle cell anemia.
Red blood Cells
• Also known as erythrocytes.
• Biconcave discs which functions to carry hemoglobin in

the circulation and are produced by the bone marrow.
• Have an average life span of 120 days.
• Average red cell count in blood is 5.4 million/microliter

in males and 4.8 million /microliter in females
• Amount of red cell count can be expressed as

hematocrit.
• Each red blood cell is 7.5 uM in diameter and 2 uM

thick and contains 29 pg of hemoglobin (mean
corpuscular hemoglobin)
• There about 2 X 1013 red blood cells in the human

body.
Red blood Cells
Hematocrit
• Measures the volume of packed red blood cells relative to whole blood.
• Reported as packed cell volume
• Used to identify conditions like anemia, polycythemia and prognosis of
diseases.
• Measured using a glass tube and a centrifuge. Blood in a glass tube is
centrifuged and separates into 3 main solid phases : (a) Red cells (b) White
blood cells (c) Platelets
• The tube which is used to measure hematocrit is called the wintrobe. This tube
is graduated from 0 mm- 100 mm in both ascending and descending order.
• HCT = (length of packed RBC X 100) / length of total cells and plasma
• Normal adult HCT should be between 40 – 54 % in males and 36-48 % in
females.
• In anemia, hematocrit is low since there are fewer numbers of circulating RBC
whereas in polycythemia, the number of RBC is high and HCT is abnormally
high.
• Smokers and patients with chronic obstructive pulmonary diseases have high
hematocrit due to chronic hypoxia.
• Increase in HCT may increase blood viscosity and total peripheral resistance,
hence may increase BP.
Hemoglobin
• Red pigment which carries oxygen in blood
• Has a molecular weight of 64 KD
• A globular protein that is made up of 4 sub units
• Each sub unit contains a heme group which is conjugated to
a polypeptide chain
• The polypeptide is referred to as the globin portion of the
molecule
• Each hemoglobin molecule is made up of two pairs of poly
peptide chains: two chains are alpha and the other two are
beta.
• Normal adult hemoglobin is known as hemoglobin A1.
• About 2.5% of hemoglobin is A2 where the beta chains are
replaced with the gamma chains.
• Patients with diabetes have glycated hemoglobin known as
HA1c.
• Fetal hemoglobin has two alpha chains and 2 gamma chains.
At any given oxygen partial pressure, fetal hemoglobin has
Hemoglobin Transport Oxygen from Lung to Peripheral Tissue
• Each heme group forms an unstable

reversible bond with an oxygen molecule,
each hemoglobin binds up to 4 oxygen
molecules.
• Binding of the first oxygen molecule is
difficult than the second and third
• This is because the conformation of
hemoglobin changes as it binds oxygen.
• Binding of oxygen to hemoglobin is said to
be cooperatively.
Red Blood Cell Synthesis
• Red blood cells are made up from a

haemopoietic stem cell in the bone marrow
• Growth is primarily regulated by the
hormone erythropoietin that is produced by
the kidneys after sensing oxygen tensions in
the blood.
• Release of this hormone into the circulation
promotes the differentiation of a
hematopoietic stem cell into erythroid
lineage.
01/21/2024 1st year MBChB/BDS - Blood Physiology 25

Erythroid cells express different cell surface receptor during maturation
Reticulocytes
• Have a life span of 1 - 2 days before being converted to an
erythrocyte
• Do not have a nucleus and endoplasmic reticulum
• They still have remnants of golgi apparatus, mitochondria, and few
other organelles
• Concentration among RBCs is normally slightly less than 1%

Regulation of Production of RBCs
• Total mass of red cells is regulated within the normal limits so
• 1) an adequate number of red cells is available to provide sufficient
transport of O2 from lungs to tissue
• 2) cells do not become so numerous that they impede blood flow

Erythropoetin
• Hormone that primarily regulated erythropoiesis
• When an individual loses blood or becomes hypoxic, Hb synthesis,
production and release of RBCs is increased
• When RBC count is above normal erythropoietic activity of BM
decreases
• These adjustments are made by erythropoietin
• Its blood levels are markedly increased in anaemia

Erythropoietin
• Is a glycoprotein with 165AA residues and 4 oligosaccharide chains

necessary for its function
• It increases the number of erythropoietin sensitive committed cells in
BM which are subsequently converted to RBC precursors
• Erythropoietin also rescues cell of the erythroid lineage from cell
death.

Erythropoietin Receptor EpoR
• Member of the cytokine

receptor subfamily
• %2 kDa protein receptor that
is bound to Jak2 protein
which has tyrosine kinase
activity
• Activation of EpoR promote
proliferation and survival of
erythroid cell lineage.

Sources
• 85% from the kidneys and 15% from the liver
• Production is markedly decreased in renal failure
• Produced by interstitial cells in peritubular capillary bed and by
perivenous hapatocytes in liver
• Also produced in the brain (protective against excitotoxic damage
triggered by hypoxia)

Regulation of haemoglobin synthesis
• Major stimuli is hypoxia (hypoxic states and thyroid hormones)
• Androgens and cobalt salts (stimulates)
• Adenosine and prostaglandins (Stimulates)
• Catecholamines (inhibits)
• Alkalosis at high altitude (stimulates)
• Synthesis reduced by oestrogens

Maturation of RBCs – Requirement for B12
and folic acid
• BM cells are among the most rapidly growing and reproducing cells in
the entire body
• Maturation and production of red cells affected by a person’s
nutritional status
• 2 vitamins are important for final maturation of RBCs – B12 and folate
• They are required for synthesis of thymidine

Formation of thymidine (Vitamin B12, Folate interaction)

Erythropoiesis requires Vitamin B12 and Folate
• Lack of either of these vitamins will result in abnormal or diminished

DNA, consequently failure of nuclear metabolism, cell division
• Cells produced are larger than normal (macrocytes) and oval in shape
• They have a normal O2 carrying capacity and a reduced half life

Vitamin B12
• Main dietary sources are meat, eggs and dairy products
• Stored in the liver (3 – 5mg)
• About 1 - 3µg of B12 required a day, hence stores last for approx 3
years

G.I. Handling of B12
• Dietary B12 binds to salivary B12 binding protein (R binder –

haptocorrin)
• R – B12 complex transported to duodenum, digested and processed by
pancreatic proteases releasing B12
• B12 binds to intrinsic factor
• Intrinsic factor – B12 complex passes to distal ileum and attaches to
receptor leading to absorption
• Absorbed B12 binds to transcobalamins which deliver it to the liver and
other cells of the body
Vitamin B12 Deficiency can be due to
• Pernicious anaemia
• Gastrectomy
• Removal of the distal ileum/ diseases of the distal ileum

Folate
• Deficiency is uncommon
• Main dietary sources are uncooked vegetables and fruits
• Destroyed by cooking for at least 10 -15 minutes
• Dietary form is predominately polyglutamate form
• Split to form monoglutamates for absorption
• Conversion is decreased by acidic food, substances found in beans
• Phenytoin decreases absorption, methotrexate inhibits absorption

Catabolism of Hb
• Old red cells are destroyed by tissue macrophages after 120 days of
life
• The globin portion is split off and heme converted to biliverdin
• Biliverdin is converted to bilirubin which is unltimately excreted in bile

Catabolism of Hb

Jaundice
• A condition that arises when free or conjugated bilirubin accumulated
ion the blood
• Skin and mucus membranes turn yellow
• Arises when total plasma bilirubin is greater than 2 mg/dL
• Reasons: (1) excess production of bilirubin eg hemolytic anemia (2)
decreased uptake of bilirubin into hepatic cells (3) Disturbed
intracellular protein binding or conjugation (4) disturbed secretion of
conjugated bilirubin into the bile canaliculi (5) intrahepatic or
extrahepatic bile duct obstruction.

Iron
• Is important for formation of Hb, myoglobin, cytochromes,
peroxidase, etc
• Total body iron is 4 – 5 g
- 65% is Hb
- 1% heme compounds
- 4% myoglobin
- 15 – 30% stored (principally as ferritin)

Iron transport and metabolism

Anemia and Polycythemia

Objectives
• By the end of this lecture the student should be able to:
1. Define anaemia.
2. Classify anaemias according to cause.
3. Classify anaemias according to red cell size.
4. Define polycythaemia.
5. Describe different types of polycythaemias and their causes.

Anaemia
• Definition
• - low Hb level for age and sex
- Adult males < 13.5g/dL
- Adult females < 12.5g/dL

Classification
- Cause
- Morphology (size, colour)

Causes of Anaemia

Sickle Cell Anaemia
• Is common in West Africans and Black Americans
• Cells have an abnormal β chain due to replacement of glutamate at
position 6 by valine
• When this Hb is exposed to low concentrations of O2 it precipitates
forming sickle cells
• Sickle cells can clog vessels and have increased red cell fragility hence
patients experience ‘crises’

Sickle Cell Anaemia
• Sickle cell trait is protective against Plasmodium falciparum malaria
(SCA common Mutoko).

Polycythemia
• Definition:
• An increase in red cell mass for a patient’s age and sex.

• Clinically revealed by increased hemoglobin and hematocrit

Polycythemia
True polycythemia
• Low serum erythropoietin (primary Neonatal
polycythemia) Polycythemia
Spurious polycythemia
• (1) polycythemia vera • Hypoxia
• Caused by (1) severe (myeloproliferative disorder caused
dehydration e.g severe induced in
by mutation in the Janus Kinase 2 ) neonates due
dehydration
• (2) primary familial and congenital to bad
• (2) Gaisbock syndrome polycythemia intrauterine
which is seen in chronic environment
smokers, alcohol abusers, • High serum erythropoietin
hypertensive male and (secondary polycythemia)
obesity • High altitude, respiratory disorders,
elevated carboxyhemoglobin, renal
disoders.

How can you differentiate between
primary and secondary
polycythemia?

Lecture 3: Hemostasis
Objectives
1. Define haemostasis.
2. Describe the main mechanisms that prevent blood loss after an injury.
3. Describe role of platelets in haemostasis.
4. Outline the mechanism of platelet plug formation.
5. Describe the mechanisms of blood coagulation
6. Describe the lysis of blood clots: fibrinolysis.
7. Describe conditions that result from abnormalities in haemostasias
including:
Bleeding tendencies:
• Due to platelet deficiency (Thrombocytopenia).
• Due to defective coagulation
8. Describe the different anticoagulants used clinically.
Hemostasis
• Formation of blood clots in walls of damaged blood vessels to prevent
blood loss and maintain blood within the vascular system
• There are 4 basic stages of haemostasis

- Constriction of blood vessel
- Formation of temporary platelet plug
- Activation of coagulation cascade
- Formation of fibrin plug

Primary Haemostasis
• Refers to the initial

response of the body to
vascular injury
• Ends with the formation

of a platelet plug.

Platelets
• To appreciate haemostasis, one should understand the structure and
function of platelets
• Also known as thrombocytes
• Are minute discs 1 – 4 µm in diameter
• They are formed in the BM from megakaryocytes
• Megakaryocytes fragment to platelets as they squeeze through
capillaries
• The normal concentration in blood is between 150 000 – 450000, and
1/3 of platelets trapped in spleen (splenectomy effect?)
• Life span is 7 – 10 days
Platelets (cont.)
• Platelets have functional characteristics of whole cells, even though
they do not have nuclei and can’t reproduce

Cell Membrane
• Cell membrane of platelets
- Has coat glycoproteins that repulse adherence to normal endothelium
but cause adherence to injured area of vessel wall
- Phospholipids, which activate multiple stages in blood clotting
- Has membrane receptors for agonists

Platelet agonist receptor
• The membrane receptors for agonists are
- Glycoprotein (gp) Ia/IIa complex – collagen receptor
- Gp Ib/IX complex – vWF, and thrombin receptor
- Gp IIb/IIIa complex – agonist induced receptor for fibrinogen and vWF

The cytoplasm contains the following
• Actin, myosin and thrombosthanin (all contractile proteins)
• Residues of both endoplasmic reticulum (store large amts of Ca2+)
and golgi apparatus
• Mitochondria and enzymes capable of forming ATP/ADP
• Enzymes that synthesise prostaglandins
• Fibrin stabilising factor
• Growth factor (PDGF)

Cytoplasm has 3 types of granules
• Dense granules – contain non protein substances that are secreted in
response to platelet activation (Calcium, serotonin, ADP)
• α granules – contain secreted proteins other than the hydrolases from
lysosomes e.g. Clotting factors, vWF, thrombospondin, fibrinogen,
fibronectin and PDGF
• Lysosomes

PDGF
• Is produced by platelets, endothelium and macrophages
• It is dimer made up of A and B subunit polypeptides
• Functions include
- Embryonic development
- Cell proliferation and migration
- Angiogenesis
- Proliferation of fibroblasts and oligodendrocyte progenitors
- Wound healing
• Implicated in pathogenesis of cancer (role of antagonists in treatment of
cancer)
Regulation of Platelet Production
• Platelet production is regulated by colony stimulating factors and
thrombopoietin
• Thrombopoietin is a circulating factor produced by liver and kidneys
• There are thrombopoietin receptors on platelets
• When platelet concentration is low unbound thrombopoietin will be
high and vice versa

Thrombopoietin
• Increases megakaryocyte production and growth, stimulates growth

of erythroid progenitor cells (with EPO) and stimulates proliferation
and prolongs survival of HSC
• In addition it sensitises platelets to aggregatory effects of agonists of
platelet aggregation

Adhesion
• Exposed collagen/vWF binds to
platelets via platelet receptors
• This will lead to Platelet
Activation

Activation and aggregation
• When platelets are activated they degranulate leading to release of
serotonin, ADP, and TXA2
• ADP attracts platelets to damaged vessel while TXA2 promotes plt
aggregation, degranulation and vasoconstriction
• There is formation of a platelet plug.

Summary of events

Secondary Haemostasis (Formation of Blood clot)
• Describe a process where exposure of blood to tissue factor initiates a

series of enzymatic reaction which ultimately results in the conversion
of fibrinogen to a fibrin blood clot by thrombin.

Secondary Haemostasis (Formation of Blood Clot)
• Blood coagulates after addition of exogenous biological
material like macerated brain extracts.
• Blood can also coagulates on its own when exposed to glass
surfaces.
• These two observation lead to the concept of intrinsic and
extrinsic blood clotting mechanisms.
• Intrinsic pathway: exposure of factor XI to collagen or glass
surfaces results in activation of factor XIII to XIIIa.
• A series of reactions are initiated which culminates in the
activation of factor FX and cleavage of prothrombin (FII) into
thrombin (FIIa). Thrombin cleaves fibrinogen to fibrin which
forms the blood clot.
• Extrinsic Pathway: Tissue factor (FIII) activates FVII and
consequently results in activation of FX, activation of
prothrombin and the formation of fibrin monomers.
Blood Coagulation
• Clotting mechanism involves a cascade of reactions in which clotting
factors are activated
• Most of the plasma proteins are synthesised by the liver (Vitamin K is
needed for synthesis of factors II, VII, IX and X)
• Clotting factors are always present in plasma in an inactive form
• When activated they act as proteolytic enzymes which activate other
inactive enzymes
• Several of the steps require Ca and plt PLs

Common Pathway

Summary

Prevention of Clotting in Normal Vascular
System
• Blood clotting in a normal vascular system is inhibited by
- Endothelium surface factors
- Antithrombin III (ATIII) and heparin

Prevention of Clotting by the Endothelium
• The most important factors are
- Smoothness of endothelial cell surface
- Layer of glycocalyx on endothelium repels clotting factors and
platelets
- Release of prostacyclin (vasodilator and inhibits plt aggregation)
- Protein bound with endothelial membrane - thrombomodulin

Natural inhibitors of coagulation
• Protein C: Thrombin binds to thrombomodulin to

form a complex which activates protein C. Protein
S is a cofactor for protein C.
• Activated protein C inactivates factor VIIa, Va,
inhibitor of
• APC also inhibits the inhibitor of tissue like
plasminogen activator.
• Plasminogen is converted to plasmin in the
presence of either thrombin, tPA or urokinase like
type plasminogen activator.
• Plasmin degrades fibrin into fibrinogen
degradation products (FDP)
• FDP are inhibitors of thrombin
Natural inhibitors of Coagulation
• Antithrombin is a serine protease inhibitor which inactivates clotting

factors.
• Heparin is a highly negatively charged polysaccharide produced by mast
cells (mainly in lungs and liver) and basophils
• It increases the effectiveness of ATIII in removing thrombin from blood
• The heparin – ATIII complex removes activated clotting factors II, IX, X, XI
and XII

Natural inhibitors of Coagulation
• Tissue factor pathway inhibitor ( TFPI) is produced by endothelial cells

• Forms a quaternary complex with Fxa, FVIIa and tissue factor. This
complex inhibits coagulation.

Fibrinolysis
• Fibrinolysis: is the process of clot dissolution.
• Plasminogen, a plasma protein, becomes trapped in the clot.
• Damaged tissues and vascular endothelium slowly release tissue
plasminogen activator (t-PA) that converts plasminogen into plasmin
(fibrinolysin).
• Plasmin digests the fibrin threads and other clotting factors and
removes the clot.

Abnormalities of Haemostasis
A- Bleeding tendencies:
1) Platelet disorders:
• Thrombocytopenia (low platelet count):
• bleeding usually from many small vessels
• many small haemorrhages occur throughout the body  purplish
blotches  thrombocytopenic purpura.
• Bleeding does not occur until the number of platelets in blood is <
50,000 /µL.
• Causes: (1) primary immune thrombocytopenia (2) heparin
injection (3) Quinine (4) infections (5) nutrient deficiency (6)
pregnancy (6) chronic alcohol abuse.

Abnormalities of Haemostasis
2) Defective coagulation
• Acquired:
• Liver disease
• Vitamin K deficiency:
• Hereditary:
• Haemophilia

Vitamin K deficiency
• A fat soluble vitamin
• Necessary for the formation of prothrombin
(factor II), factor VII, IX and X.
• Normally synthesized by bacteria in the intestinal
tract (except neonates).
• Most common cause is failure of the liver to
secrete bile into the GIT either due to obstruction
of bile ducts or as a result of liver disease.
• Lack of bile prevents adequate fat digestion and
absorption.

Haemophilia
• X-linked disease, occur in boys, girls are carriers.
• 85% due to factor VIII deficiency: haemphilia A or
classic haemophilia
• 15% due to factor IX deficiency: haemophilia B.
• Bleeding can have various degrees of severity
depending on the severity of the genetic deficiency.
• Mild trauma can cause severe and prolonged bleeding.
• Rx: injection the deficient factor.

Anticoagulants for clinical use
• In-vivo (inside the body)
• IV: Heparin
• Oral: Coumarins (dicumarol or warfarin)
• In-vitro (outside the body)
• Heparin
• Calcium-deionizing agents

Differences between heparin and
coumarins
Heparin Coumarins
Animal origin Plant origin
Instant action Delayed (1-2 days)
Action lasts for up to 4 hr Lasts for days
Given IV or IM Orally
Acts by combining to ATIII Acts by competitive inhibition
increasing its effectiveness in of Vit K inhibiting the formation
removing thrombin of factors II, VII, IX and X
Acts in-vivo and in-vitro Only in-vivo

Antidote: protamine sulphate Vitamin K
In-vitro anticoagulants
• Heparin
• Calcium-deionizing agents:
• Oxalate compounds: precipitation of calcium oxalate
(toxic so cannot be used for blood transfusion).
• Citrate compounds: combines with calcium in the
blood and gives an un-ionized calcium compound (can
be used in blood transfusion).

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Blood Physiology

Ben Bhunu, Ph.D Biomed.

• Granulocytes AKA polymorphonuclear

• Basically, fall into 3 main categories (a)

• Serum is simply plasma without fibrinogen.

• Plasma constitutes 92% water and 8& solids.

• Clotting Factors: Play an essential role in blood clotting.

• Examples: Fibrinogen, Prothrombin, tissue thromboplastin/ tissue factor, ionized

• Activated by damage to the endothelium and blood exposure to collagen.

• Collagen is normally found beneath the endothelium of blood vessels.

• Deficiency in clotting factors results in conditions like hemophilia and Von

• Albumin: main protein that controls oncotic pressure and is a transporter

• Globulins: Group of blood proteins with a globular structure. Divided into

• Immunoglobins: These protein play a key role in the defense against

• Disorders in the production of immunoglobulins as in congenital and

• Key in the manufacture of vaccines.

• Enzymes: Alpha antitrypsin is produced by the liver and breaks down

• Other enzymes may be tissue specific and also found in blood as

• Hormones: angiotensin, testosterone ,estrogen, progesterone,

• Malabsorption of proteins may leads to low plasma protein

• Liver diseases and renal insufficiency may results in low plasma

• Thrombotic thrombocytopenic purpura (TPP). Type of hemolytic anemia

• The unbroken vWF multimers cause increased platelet adhesion and

• Clotting disorders: Hemophilia A and B

• Hemophilia A is due to deficiency of factor VIII

• Hemophilia B is due to deficiency in factor IX

• Symptoms involved hemarthrosis (bleeding in joints) and hematomas

• Immunodeficiency: Bruton disease (agammaglobulinemia) : Failure to

• Edema (low plasma protein) : Decreased plasma oncotic pressure results

• Biconcave discs which functions to carry hemoglobin in

• Have an average life span of 120 days.

• Average red cell count in blood is 5.4 million/microliter

• Amount of red cell count can be expressed as

• Each red blood cell is 7.5 uM in diameter and 2 uM

• There about 2 X 1013 red blood cells in the human

• Each heme group forms an unstable

• Red blood cells are made up from a

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• Is a glycoprotein with 165AA residues and 4 oligosaccharide chains

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• Member of the cytokine

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• Lack of either of these vitamins will result in abnormal or diminished

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• Dietary B12 binds to salivary B12 binding protein (R binder –

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