This document summarizes key aspects of blood physiology. It describes that blood is a connective tissue composed of plasma and formed elements including red blood cells, white blood cells and platelets. It transports oxygen, nutrients, waste products and hormones throughout the body. Red blood cells are produced through erythropoiesis in the bone marrow and contain hemoglobin which reversibly binds oxygen. Old red blood cells are destroyed and their components recycled or excreted. Disorders can occur if red blood cell counts or hemoglobin levels become too high or low.

1. BLOOD PHYSIOLOGY

2. Physical characteristics and volume
 It is a viscous fluid connective tissue, which is heavier and thicker
than water.
 Color varies from red (oxygen-rich) to dark red (oxygen-poor)
 The pH of blood is 7.35–7.45 and its salt content is 0.9%
 Temperature is 38C, slightly higher than “normal” body
temperature
 Blood accounts for approximately 8% of body weight
 Average volume: 5–6 L (males), 4–5 L (females)

3. Functions of Blood
 Substance distribution (plasma proteins…
 Transport oxygen from the lungs and nutrients from the
digestive tract
 Transport metabolic wastes from cells to the lungs and to
kidneys for elimination
 Transport hormones from endocrine glands to target organs

4. Functions of Blood…cont’d
 Blood maintains:
 Body temperature by absorbing and distributing heat
 Normal pH in body tissues using buffer systems
(e.g., H+, HCO3-)
 Adequate fluid volume in the circulatory system
 Blood prevents blood loss by:
 Activating plasma proteins and platelets
 Initiating clot formation when a vessel is broken
 Blood prevents infection by:
 Synthesizing and utilizing antibodies
 Activating WBCs to defend the body against foreign invaders

5. Composition of Blood
 Blood is the body’s only fluid connective tissue
 It is composed of -liquid plasma (55%) and
-formed elements (45%)
 Formed elements include:
 Erythrocytes, or red blood cells (RBCs)
 Leukocytes, or white blood cells (WBCs)
 Thrombocytes, or Platelets
 Hematocrit – the percentage or proportion of blood cell to blood
volume

6. Components of Whole Blood
Withdraw blood
and place in tube
1 2
Centrifuge
Plasma
(55% of whole blood)
Formed
elements
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
Erythrocytes
(45% of whole blood)

7. Plasma
 It is the liquid portion of blood
 It makes up 55% of the blood volume
 Has the osmolality of 300 mosm/lit
Composition of plasma
 Blood plasma is composed of
1. Water (90%)
2. Organic constituents (9%)
 Plasma proteins: albumin, globulins, clotting proteins, etc.
 Lipids, lipoproteins, phospholipids
 Hormones and enzymes
 Nutrients: CHO, vitamins, amino acids, fats
 Metabolic waste products: urea, creatinine
3. Inorganic constituents: electrolytes (1%)
4. Respiratory gases – oxygen and carbon dioxide

8. Plasma…cont’d
 There are 3 principal plasma proteins
Albumin: 4 g/dl
Globulin: 2.7 g/dl
Fibrinogen: 0.3 g/dl
 Plasma proteins are synthesized by
 # hepatocytes
 lymphocytes
 platelets
 endothelial cells

9. Plasma…cont’d
Function of plasma proteins
1. Immunologic function: γ-globulins are immunoglobulins
(antibodies)
2. Haemostasis: fibrinogen, prothrombin and most other clotting
factors are plasma proteins
3. Transport of hormones, electrolytes and drugs.
4. pH regulation (buffering function)
5. Maintenance of plasma osmotic pressure (mainly by albumin)
6. Enzymatic and hormonal function

10. Plasma…cont’d
1. Albumin (60%):
 is formed in the liver and constitutes about 60% of the plasma
proteins.
 helps to maintain blood volume, for it can not easily pass
through the capillary membrane.
 During malnourished conditions (deficiency of protein intake),
blood volume decreases due to decreased albumin content.
 Albumin also serves in transporting nutrients (lipids, hormones,
bilirubin etc)

11. Plasma…cont’d
2. Globulin (40%)
 3-suptypes: alpha, beta, and gamma globulins.
 about 40% of the total plasma protein.
 Alpha and beta globulins are made in the liver.
 Alpha and beta globulins transport lipoproteins, Fe 2+, hormones, enzymes,
nutrients, and other substances in the body.
 Gamma globulins act as immunoglobulin's (or antibodies) and help in
defending our body against infections.
 Made in Lymphoid tissue
3. Fibrinogen (2-4 %):
Fibrinogen is synthesized in the liver and is mainly involved in blood clotting

12. Erythrocytes (Red blood cells)
 Major content of RBCs is Hb (97% )
 Size: Diameter 7.5 µm
Thickness 1 and 2 µm
 Shape: Biconcave disk
No nucleus, no organelles
 RBC Count:
 M = 5.2 millions/mm3
 F = 4.6 millions/mm3
 Hematocrit: percentage of blood cells
M = 42-48%, average-45%
F = 38-43%- average-42%

13. Erythrocytes…cont’d
 Function
 Transport of O2 and CO2
 Regulation of acid-base balance.
 Hemoglobin (Hb)
 Male 15 g/dl
 Female 14 g/dl
 Plasma membrane of RBCs is comprised of flexible
proteins
 Allow them to change shape as necessary
 ATP is generated anaerobically

14. Production of Erythrocytes
 Hematopoiesis – blood cell formation
 Areas of production of RBCs
A. Embryonic life
• RBC are produced in the liver, spleen and lymph
nodes
B. Infants (till 5 years)
• RBC are produced in marrow of all bones
C. Adults (after 20)
– Membranous bones like ribs, skull, sternum, vertebrae,
and pelvic bones, but not in long bones like femur or

15. 15
Production of Erythrocytes…cont’d
Fig. Relative rates of red blood cell production in the bone marrow of
different bones at different ages

16. Production of Erythrocytes…cont’d
 In adult, RBC and other blood cells are produced in the bone
marrow from a single type of cells called pluripotent
hematopoietic stem cells.
 These cells, then differentiate and form committed stem cells
that produce only specific types of blood cells

17. Production of Erythrocytes…cont’d

18. Production of Erythrocytes…cont’d
Proliferation phase Maturation phase

19.  Circulating erythrocytes – the number remains constant (balanced
RBC production and destruction)
 Too few red blood cells (Anemia) leads to tissue hypoxia
 Too many red blood cells (Polycethemia) causes increased
blood viscosity
 Erythropoiesis requires diets rich in:
 Iron, and vit. B complex (vit-B12, folic acid)
 Vit-B12 and folic acid are essential for the RBC maturation
(Necessary for the synthesis of DNA of RBC)
Regulation and Requirements for Erythropoiesis

20. Regulation for Erythropoiesis…cont’d
 Erythropoiesis is hormonally controlled.
 Hormones accelerating erythropoiesis:
 Erythropoietin (EP) from JG-cells and hepatocytes
 GH, T3/T4, Androgens (testosterone)
 Intrinsic factor from parietal cells of the stomach (absorb B12)
 Liver plays a critical role in RBC formation as site of globin
synthesis, as a storage area of iron and vit-B12

21. Erythropoietin Mechanism
Reduces O2
levels in blood
Erythropoietin
stimulates red
bone marrow
Enhanced
erythropoiesis
increases RBC
count
Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased availability of
O2 in blood, or increased
tissue demands for O2
Start
Kidney 85% and
liver 15 % releases
erythropoietin
Increases
O2-carrying
ability of blood

22. 22
Erythropoietin Mechanism…cont’d

23. 23
Relation of Erythropoietin to Hct ratio
 Erythropoietin vs. Hct
 A decrease in Ht ratio increases
the concentration of EPO level
making their relations inverse.

24. Hemoglobin
 Hb in RBCs is means for transport of respiratory gases
 Normal concentration; 15 g/dl in M and 14 g/dl in F
Composition:
 Composed of a protein globin and heme
 4 heme molecules conjugated with 4 globin molecules to form Hb
 In adult Hb, the globin part has 4 polypeptide chains
2 α-chains, each made up of 141 aa residues
2 β-chains, each made up of 146 aa residues
Types of Hb
1. Adult Hb (HbA-α2 β2)
2. Fetal Hb (HbF -α2 γ2)
3. Sickled Hb (HbS - α2 β2)
 Sickled Hb, in two of the β-chains at position-6 valine is
wrongly substituted for glutamate

25. Hemoglobin…cont’d

26. Hemoglobin…cont’d
 Hb reversibly binds with O2 and most O2 in the blood is transported in
combination with Hb
 Each heme group bears an atom of iron, which can bind to one O2
molecule
 Each Hb molecule can transport four molecules of oxygen
 Oxyhemoglobin – hemoglobin bound to oxygen
 Oxygen loading takes place in the lungs
 Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues
 Carbaminohemoglobin – hemoglobin bound to carbon dioxide
 Carbon dioxide loading takes place in the tissues and is returned to
lungs to be eliminated in expired air

27. Destruction of Erythrocytes
 The life span of an erythrocyte is 120 days
 Old erythrocytes become rigid and fragile, and their hemoglobin
begins to degenerate
 Dying erythrocytes are engulfed by macrophages
 Heme and globin are separated and the iron is recovered for
reuse
 The heme part is converted into bilirubin
 Bilirubin is the main component of biliary secretion

28. Destruction of Erythrocytes…cont’d
 Jaundice
Yellow coloration of the skin and sclera
Due to excessive bilirubin in plasma (>1.5 mg/dl)
Normal plasma bilirubin level is 0.5 mg/dl
In case of jaundice, bilirubin level is elevated up to 40 mg/dl
 Types/ causes of jaundice
1. Hemolytic jaundice: ↑RBC destruction
2. Obstructive jaundice:
a. Obstruction of bile ducts by stone
b. Obstruction of bile ducts by head of pancreas

29. 29
Destruction of Erythrocytes…cont’d
Steps in the destruction of RBC
1. RBC  Globin + Heme
2. Globin  broken to AA’s  used for protein synthesis
3. Heme  Fe2+ + poryphrine rings
4. Fe 2+  stored in spleen and liver or reused by bone marrow
for new Hb synthesis
5. Pyrol rings  oxidation to green pigment called Biliverdin and
later reduced to bilirubin
a. bilirubin + serum albumin  go and reach liver
b. Bilirubin conjugates with glucuronic acid in liver
c. Liver releases bilirubin as bile to Small intestine
d. Bacterrias change bilirubin into:
Stercobilinogen  stercobilin  feces (brown color)
Uribilinogen  Urobilin  Urine (yellow)

30. Destruction of Erythrocytes…cont’d

32. Erythrocyte Disorder
 It is a condition char/zed by a decrease in the hemoglobin level,
RBC count or both leading to decrease in the O2 carrying capacity
of the blood or increasing RBC count
1. Anemia: decreased RBC number and lower concentration of
hemoglobin (Hb) in the circulating blood.
 diminished O2-carrying capacity of the blood.
 excessive loss (bleeding), or destruction (hemolysis), or lower
production of RBC (lack of nutrition) in the circulation.

33. Erythrocyte Disorders…cont’d
 Types of Anemia's include
a. Blood loss anemia
b. Aplastic anemia
c. Megaloblastic anemia
d. Hemolytic anemia

34. White blood cell (Leukocytes)

35. Leukocytes (White blood cell)
 Leukocytes, (complete cells): Contain nucleus, and other
organelles but no Hb
 Normal WBC count: 4000 – 11000/mm3 (Aver=7000/mm3 )
 Are highly mobile and reach into tissue fluids
 Function: defense/protection against disease
a. by direct destruction (e.g., Phagocytosis)
b. by producing : i. antibodies ii. sensitized lymphocytes
35

36. 36
Formation of leukocytes

37. 37
Type of WBC …cont’d
Macrophages
37

38. Types of WBC
38
1.Granulocytes –Polymorphonuclear (i.e. their nuclei have 3-5
lobes)
• Attack pathogen by phagocytosis
a. Neutrophils (~ 62%, 3000-7000/mm3), life span 4-5 days
 Have multilobed nuclei ( 2-5 lobes)
 Phagocytic cells (ingest bacteria)
 have enzymes to digest bacteria

39. b. Eosinophils (~ 2-3%, 100-440/mm3), life span 4-5 days
 Are bi-lobed and weak phagocytes .
 Have granules in the cytoplasm that have enzymes
 Phagocytize antigen-antibody complexes and destroy them
 Their number increases during asthma and other allergic attacks
c. Basophiles (~ 0.1-0.4%, 20-50/mm3), life span 4-5 days
 Have granules
 Produce heparin, so act as natural inhibitors of blood clotting.
 synthesize & store histamine, bradykinin, and serotonin
39
Types of WBC…

40. 2. Agranulocytes.
a. Lymphocytes(~30%,1500-3500/mm3),life span weeks or months
• Have no granules and the nucleus is not lobed
• Produced in the bone marrow and lymphogenous organs
(spleen, thymus, tonsils , payer’s patches etc)
• Are responsible for specific immunity that consists of:
a. Cellular immunity (T lymphocyt)
b. Humeral immunity (B lymphocyte)
b. Monocytes (~5 %, 100-700/mm3), 20 hrs, circulate in blood
and change into macrophages that attach to tissues
 They are highly phagocytic cells
 They are the largest WBCs
 They leave the circulation, enter tissue, and differentiate into
macrophages
40
Types of WBC…cont’d

41. 41
The tissue macrophage system (reticuloendothelial system)
Monocytes are formed in the bone marrow

Enter the circulation

Leave the circulation, enter the tissue,

↑size, ↑lysosomal activities

Become tissue macrophages

Lungs Skin Liver Brain Bone Spleen
     
Alveolar Histocytic Kupffer Microgleal Osteoclasts
Macrophages cells cells Reticular cells
lymph nodes
41

42. Mechanisms of WBC mobility through the tissues
1.Diapedesis:WBC approach the capillary
wall and squeeze out through the
pores(e.g. Neutrophils, Monocytes etc)
2. Amoeboid motion: Produce pseudopodia
and reach the microbes in the tissues.
3. Chemotaxis: WBC are attracted by
chemicals or toxins produced by microbes
or inflamed tissues(Eosinophils)
4. Phagocytosis: engulfing & destroying
the pathogens in the tissues (e.g.,
Neutrophils, macrophages etc.)
42

43. Mechanism of Phagocytosis
1. Opsonization
2. Attachment
3. Engulfment
4. Intracellular killing by
producing:
 Lysosomes, and
 oxidizing agents like lipases,
peroxisomes, H2O2, OH- ions
are produced from
macrophages that are lethal
for bacterial cell membranes.
43

44. Activation of T-Lymphocytes
The different types of T-cells include:
a. Killer (cytotoxic) T-cells: Kill pathogens directly and stimulate
other macrophages for phagocytosis
b. T-memory cells: Remain as reserve in the lymph node and
protect when the same type pathogen attacks the body again
c. Helper T- cells: support or help the B-cells by producing
chemicals known as Lymphokines or (cytokines)
 HIV, the virus that causes AIDS normally infects helper T-cells
(and other immune cells) and inactivates the total immune
response
d. Suppressor T-Cells: Regulate the immunological response of
T-and B-cells

45. Immunoglobulins
 B-cells that bind with an antigen will
subsequently differentiate into Plasma cells
& Memory cells
 Plasma cells - begin to produce
antibodies (up to 2,000 per second)
 Memory cells - remain dormant until a
person is again exposed to the same
antigen
 There are 5-classes of antibodies
 IgA, IgE, IgD, IgG and IgM

46. Five classes of Immunoglobulin
 IgM (10%) = are pentameters and is 1st or early antibody that
appears in circulation after infection.
• It forms the natural antibodies of the ABO blood antigens
 IgG(75%) - crosses' placenta and provides passive defense of the
fetus
 IgE (0.004%) = increased in allergic reactions and parasite
infections.
• It can bind to mast cells and induce the liberation of histamine
(asthma, Anaphylaxis)
 IgA(15%) - found in secretions of digestive (saliva), respiratory
(bronchus), urinary, & reproductive systems, as well as in breast
milk and in tears
 IgD (0.2%) = Are found on surfaces of B-cells and help to
recognize the antigen, otherwise other function is not known

47. Group assignment
####Mechanism of action of antibodies
(direct attack and complement system)

48. 48
1. Leukemia - increased WBC No. or cancerous production of
WBC.
• Their increased production takes the space of platelets & RBC
causing anemia + impaired blood clotting
 Increased WBC causes
A. Metabolic starvation:
• WBC consume too much metabolic substrates. Thus energy
source is depleted and too much use of a.a by cancerous cells
causes rapid deterioration of other body tissues.
B. Anemia and increased bleeding tendency can occur.
2. Leucopenia - decreased production of WBC.
• Bone marrow stops producing WBC.
• It can be caused by: - Drug poison, X-rays
Disturbance of WBC

49. Platelets (Thrombocytes)
49

50. Platelet
 Platelets are small disk-shaped cell fragments that emerge from
megakaryocytes in red bone marrow (2-4 microns in diameter)
 Life span : 4-12 days
 Platelet count :150,000 -300,000 /mm3 of blood
 Cytoplasm: have no nucleus and thus can not reproduce
 They release some chemicals in their cytoplasm (prostaglandins,
thromboxane, fibrin stabilizing factor, phospholipids, minerals and
growth factor etc).
 Platelets function in the blood clotting mechanism by forming a
temporary plug that helps seal breaks in blood vessels
50

51. Genesis of Platelets
 The stem cell for platelets is the hemocytoblast
 The sequential developmental pathway is hemocytoblast 
megakaryoblast  promegakaryocyte  megakaryocyte 
platelets
Figure 17.12
51

52. Properties of platelets
1. Adhesiveness : platelets stick when they come in contact with
wet and rough surfaces.
 Normally, their glycoprotein (structure in their cell membranes)
prevent adhesiveness to the normal endothelium)
2. Aggregation: When platelets are activated, they usually group
together
 Their aggregation and stickiness is mainly due to ADP and
Thromboxane A2 found in their cytoplasm
3. Agglutination: Platelets clump together and form clots
52

53. Indi. assignment:
ABO blood grouping and blood transfusion
Group assignment
The mechanism of hemostasis / blood clotting