Haemopoietic

Physiology
SYLLABUS
Blood as a Body Fluid: (P. 809)
Composition, physical characteristics and functions of Blood
Plasma: (P. 809)
Normal constituents, plasma proteins: types, concentrations, properties, functions.
Red Blood Cells: (P. 810)
Types, distribution, overview of hematopoiesis (P. 810)
Erythrocytes:
Morphology, Functions, Fate, Normal count, PCV, ESR (P. 811), MCV, MCH, MCHC, Fragility, Hemolysis.
Erythropoiesis: (P. 812)
Definition, Stages (P. 812), Regulating factors (P. 813), RBC indices (P. 810) and Clinical usefulness.
Anemia: (P. 815)
White Blood Cells: (P. 815)
Classification, Morphology, Development, Normal count,
Platelets (P. 818):
Morphology, functions. III
Blood Groups: (P. 819)
Agglutinogens, Agglutinins, Landsteiner’s law (P. 819), ABO group, Rh group (P. 819)
Blood transfusion: (P. 819)
Relation to blood groups, Indications (P. 819), Hazards (P. 820)
Inheritance, Erythroblastosis foetalis, Hemolytic disease of the newborn
Haemostasis: (P. 820)
Physiology of coagulation: Intrinsic and extrinsic mechanism (P. 822), Clot retraction, Fibrinolysis (P. 823),
Tests for clotting (P. 823) Natural and other anticoagulants

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PHYSIOLOGY

BLOOD  Liquid portion of the blood

 Blood is a red fluid that fills the cardiovascular system. Plasma
Characteristics:
- Alkaline (pH: 7.35 to 7.45)
- Red in colour with peculiar odour Water Solid Gases
- Specific gravity 1055 to 1060 (at 15 c) 0 (CO2, O2, N2)

Composition:
- Consists of; Plasma (55%)
Inorganic Organic
Blood cells (45%)
Functions:
- In respiration: Transport of O2 to tissue and
CO2 to lungs Anions Cations Colloids Crystalloids
– – + + 2+
- Distribution of nutrients to all parts of body Cl , HCO3 Na ,K , ca - Plasma protein Glucose,
3- 2- 2+
PO4 , SO4 Mg etc - Plasma lipid Urea, Uric
- In excretion: Transport waste material to
acid
organs of excretion
- Transport medium for various hormones, Serum = Plasma - fibrinogen - factors used with
chemicals, drugs etc. coagulation
- Maintenance of acid - base balance of body III
Blood = Serum + clot
- Maintenance of body temperature
- Protection of body by neutrophils, monocytes Plasma proteins
antibodies
 Refer Biochemistry
- Store house of water, electrolyte and nutrients
for cells of body. Functions of plasma protein
- Maintaining internal environment of body i.e. - Help in coagulation of blood
homeostasis. - Help in defense mechanism of body
Thus, blood helps in respiration, transport,
- Help in transport mechanism
homeostasis, temperature regulation and
protection. - Help in maintenance of osmotic pressure in
blood
PLASMA
- Help in regulation of acid - base balance
Past Questions:
- Help in viscosity of blood
1. Plasma proteins (2) [08 July, 08 Jan]
- Help in erythrocyte sedimentation rate
2. Functions of plasma proteins
(3) [09 July, 06 June, 02 June] - Help in suspension stability of red blood cells
3. Oncotic pressure (2) [09 Jan] - Help in production of trephine substances
4. Oedema (3) [04 Dec] - Help as reserve proteins

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RED BLOOD CELLS Functions:

- Transport of gases like O2, CO2’etc
 RBC/Erythrocytes constitute major part of cellular
component of blood. - Acid - base balance
- Formation of bilirubin
 4 - 5.5 million /l
- Maintenance of viscosity of blood
Haemopoiesis
Fate of RBC
- Yolk sac: starts from 3rd week of intrauterine
(IU) life Blood RE cells
Old RBC Phagocytosis
- Liver and spleen: from 3rd month of IU life. RBC
th Lysis
- Bone marrow (from 5 month onward): Lysis
by haptoglobin
 After birth haemopoiesis; only by bone Haemoglobin Haemoglobin
marrow but in case of emergency liver and
spleen also involve. Haem Globin Aminoacid Globin Haem
- Destroyed in RE cells (spleen, liver, etc) pool
- Life span: 120 days
Transferrin Fe Biliverdin Carbon
Morphology: Monoxide
- Biconcave discs
Ferritin
- Diameter: 7.2 m (5.5 to 8.5 m) (stored)
Thickness: Transported to liver by Bilirubin
 2.2 m (at periphery) albumin binding

 1 m (at centre) Red blood cell indices:

- Surface area: 120 sq  i. Packed cell volume (PCV)
III
- Average volume: 90 - 95 m 3
- It is the volume of red cells in 100 ml of whole
blood.
- Value is equal to haematocrit value
- Its value is 45 ml (i.e. Haematocrit = 45%)
Variations in PCV:
Increase in PCV Decrease in PCV
1. Polycythemia 1. Anemia
2. Dehydration 2. Cirrhosis of liver
3. Dengue shock syndrome: 3. Pregnancy
Dengue fever 4. Hemorrhage due to
Ectopic pregnancy
ii. Mean corpuscular volume (MCV)
Benefits of biconcave shape:
- Average volume of an erythrocyte
- Quick gas exchange
Volume of RBC in 100 ml.blood(PCV)
- More surface area for gas exchange. - MCV= Number of RBC in 100 ml of blood (Count)
- More flexibility with an ability to fold and pass via
- Normal value: 873 (80 - 94 3)
narrow capillaries
-  in megaloblastic anemia (macrocytosis)
- Ability to withstand some osmotic change
 in iron deficiency anemia (microcytosis)
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iii. Mean Corpuscular Haemoglobin (MCH) Variations in ESR

- Average amount of Hb present in each RBC A. Physiological variation:
Hb present in 100 ml blood 1. Age:
- MCH= Number of cells present in 100 ml blood
- ESR is less in children and infants because of
- Disadvantage is, it considers absolute amount more number of RBCs.
of Hb in each cells on average and not consider 2. Sex:
it in relation to RBC size i.e. in macrocytic - It is more in females than in males because
anemia, its value will be higher though it is of less number of RBCs.
anemia. 3. Menstruation:
- Normal value: 26 - 34 ρg - The ESR increase during menstruation
 > 34 = Hyperchromic because of loss of blood and RBCs
 < 26 = Hypochromic 4. Pregnancy:
iv. Mean Corpuscular Haemoglobin concentration - From 3rd month to parturition, ESR increase
(MCHC) up to 35mm in 1 hour because of
- Amount of Hb present in 100 ml of RBC hemodilution.
amount of Hb B. Pathological variation:
- MCHC=
volume of RBCs containing the Hb ESR increases in disease such as the following
- Normal value: 32 – 36 gm/dl (19.9–22.3 conditions:
mmol/L). 1. Tuberculosis
- Lower in hypochromic anemia but never higher 2. All types of anemia except sickle cell anemia
than normal. 3. Malignant tumors
v. Colour index (CI) 4. Rheumatoid arthritis III
- It denotes the ratio of haemoglobin to RBC. 5. Rheumatic fever
Hb% 6. Liver diseases
CI = RBC%
ESR decreases in the following conditions:
- Normal range = range: 0.85-1.15) 1. Allergic conditions
- It is an insignificant index, because normal 2. Sickle cell anemia
range of RBC is very wide. 3. Peptone shock
Erythrocyte sedimentation Rate (ESR) 4. Polycythemia
- Hight of plasma separated in mm per hour 5. Severe leukocytosis
when blood is allowed to stand in narrow Fragility and Haemolysis
vertical tube. - Breakage or lysis of erythrocytes with releases
2nd hr. reading of Hb is haemolysis.
1st hr. reading +
2
- Mean ESR =
2
mm/hr - The tendency to haemolysis is fragility.
- Westergren pipette and Wintrobe's tube is - Fragility is higher in spherocytosis, G6PD
used to measure ESR deficiency, etc.
- Normal value: Male: 4mm/hr - Haemolysis seen in infection (malaria), snake
venom, drugs induced (quinine), toxic material
Female: 8 mm/hr
- Results in jaundice and anemia
- It occurs due to Rouleaux formation.

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ERYTHROPOIESIS Stages of erythropoiesis

Past Questions: [12, 10, 09, 08, 06, 05, 04, 03, 02]
1. Define erythropoiesis. Mention the stages of i. Stem cell:
erythropoiesis and state in which stage - Pluripotent, common ancestor of all type of
haemoglobin appears. What are the differences blood cells
between adult and fetal haemoglobin. ii. Committed stem cell:
[1+3+2=6][10 Jan] - Committed to produce blood cells, either
2. List the different stages of erythropoiesis and myeloid series or lymphocyte series
describe its regulation. [3+2=5] [09 Jan] - Give rise to progenitor cell
3. List the stages of erythropoiesis and describe its iii. Progenitor cells:
regulation. [3+3=6] [06 Dec]
- 2 types that forms RBC only
4. List the different stages of erythropoiesis and
BFV-E (Burst forming unit of erythrocyte series)
describe its regulation. [3+2=5] [09 Jan]
- Single of this form large number of cells
5. List the stages of erythropoiesis and describe its
regulation. [3+3=6] [06 Dec] CFU-E (Colony forming unit of erythrocyte series)
6. Define erythropoiesis. Mention the stages and - Gives rise to smaller number of cell than BFU-E
factors influencing erythropoiesis[1+5=6] [04 Dec] - Assumed to be formed from BFU - E and are
7. Enumerate the stages of erythropoiesis. State the most differentiated progenitor cells.
factors regulating erythropoiesis iv. Pronormoblast (Proerythroblast)
[2+3=5, 6, 4+4=8] [08 July, 03 June, 03 Dec, 02 June] - First blast cell of erythrocyte series
8. What are the sites of erythropoiesis in adults? List - 15 - 20  diameter
the stages of erythropoiesis. [1 + 2 =3] [05 June]
- Nucleus: with many nucleoli, basophilic, 12 
9. Describe factors regulating erythropoiesis
III diameter
[3][04 June] - Cytoplasm: basophilic
 Process of formation of erythrocytes: - Shows mitosis, Hb absent
Stem cell v. Early Normoblast
 - 10 - 17 m diameter
Committed stem cell
- Nucleus: large, mitosis present

- Cytoplasm: Basophilic due to plenty RNA
Progenitor cells
- In late stage, Hb appears

Proerythroblast (pronormoblast) vi. Intermediate Normoblast:
 - 10 - 14 m diameter
Early normoblast - Polychromatophilic normoblast
 - Nucleus: Smaller
Intermediate normoblast - Mitosis present early but later plenty Hb
 appears and mitosis stops.
Late normoblast vii. Late Normoblast:
 - 7 - 10 m diameter
Reticulocyte - Cytoplasm mostly eosinophilic due to more Hb
 - Nucleus: small, pyknotic
Erythrocyte
- Orthochromatic normoblasts

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viii. Reticulocyte bed in kidney and also by perivenous

- Cell eosinophilic but retain basophilic hepatocyte in liver.
reticulum - Stimulated by hypoxia, anaemia, low blood
- Hb synthesis continues: no mitosis volume, low blood pressure, epinephrine, nor -
- Released into blood epinephrine, testosterone
ix. Erythroblast Production
- 7.2 m diameter - Mainly (85%) secreted by kidneys probably by
interstitial cells (or cells in the endothelium) of
- Fully eosinophilic
the peritubular capillaries.
Important events during erythropoiesis:
- 15% produced by extra renal sources like liver
Stage of erythropoiesis Important event
parenchymal cells and cells of tissue
Proerythroblast Synthesis of hemoglobin macrophage system.
starts Erythropoietin promotes the following processes:
Early normoblast Nucleoli disappear - Production of proerythroblasts from CFU-E of
Intermediate Hemoglobin starts to the bone marrow
normoblast appear - Development of proerythroblasts into matured
Late normoblast Nucleolus disappears RBCs through the several stages- early
normoblast, intermediate normoblast, late
Reticulocyte Reticulum is formed
normoblast and reticulocyte.
Cell enters capillary from
- Release of matured erythrocytes into blood. Even
site or production
some reticulocytes (immature erythrocytes) are
Matured RBC Reticulum disappears cell released along with matured RBCs. III
attains biconcavity c. Iron: Content of Hb
Factors affecting Erythropoiesis: d. Vitamin B12, folic acid: for DNA synthesis
[10, 09, 08, 06, 05, 04, 03,02] e. Intrinsic factor: for absorption of Vit-B12
a. Hypoxia:
Regulation of Erythropoiesis
- Hypoxia means lack of oxygen at tissue level.
- It is the mot potent stimulus for the production
of RBCs.
- Hypoxia causes stimulation of bone marrow General factors Special maturation
thereby increases RBC production. factors
- This effect is mediated by erythropoietin. Hypoxia
b. Erythropoietin (Or Haemopoietin or Erythrocyte 1. Dietary factors
stimulating factor (ESF) or Erythropoiesis - Iron
stimulating hormone (ESH): 2. Extrinsic factor
- Glycoprotein hormone (74% protein, and 26% - Vitamin B12
carbohydrates) - Folic Acid

- Secreted by hormone producing interstitial 3. Castle's intrinsic

factors
connective tissue cells of peritubular capillary

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4. Describe the origin and development of

ANAEMIA lymphocytes. State the functions of T and B
 Anaemia is reduction in O2 – transporting capacity lymphocytes. [3+2=5] [11 July]
of blood which usually stems from a reduction of 5. Describe the functions of lymphocytes.[3][05 June]
total circulating red cell mass to below normal
6. Describe with the help of suitable diagrams the
amounts.
morphology and functions of different white
Cause: blood cells. [7][07 July]
i. Blood loss:  These nucleated blood cells are required for
- Trauma protection of body against infections, antigens,
- Haemorrhagic anaemia malignancy.
- Peptic ulcer Leucocytes
- Hookworm infestation
ii.  RBC formation:
Granulocytes Agranulocytes
- Impaired Fe level: Fe deficiency anaemia
-  vit-B12 and folic acid: Megaloblasticanaemia
iii. RBC destruction (hemolysis): Neutrophils Eosinophils Lymphocytes Monocytes
- Hemolytic anaemia
Basophils
- Sickle celled anaemia
Large Small
- Thalassemia
- Spherocytosis Properties of WBCs
iv. Fluid overload: 1. Diapedesis:
- Hypovolemia  It is the process by which the leukocytes
III
- Pregnancy squeeze through the narrow blood vessels.
Treatment: 2. Ameboid movement:
- Oral iron along with vit C  Neutrophils, monocytes and lymphocytes show
- Parenteral Fe given concurrently with amebic movement, characterized by protrusion
erythropoietin of the cytoplasm and change in the shape.
- Blood transfusions 3. Chemotaxis:
- Hyperbaric oxygenation  Chemotaxis is the attraction of WBCs towards
- Vitamin supplement: B12, folic acid the injured tissues by the chemical substances
released at the site of injury.
- Erythropoiesis stimulating agent
4. Opsonization:
WHITE BLOOD CELLS  Opsonins are antibodies against bacteria.
Past Questions:  The principal opsonins are immunoglobulin of
IgG group and complement proteins.
1. Describe the various stages of leucopoiesis with
suitable diagram and describe the functions of  They coat the bacteria and make them tasty to
neutrophils. [3 + 3 = 6] [06 June] the phagocytes, a process called
'opsonization'.
2. Classify leucocytes and write their functions
briefly. [5][09 July] 5. Phagocytosis:
3. Name different types of WBC and describe the  Neutrophils and monocytes engulf the foreign
functions of neutrophil. [1 + 4 = 5] [05 Dec] body by means of phagocytosis.

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Cells Morphology Function

i. Neutrophil - 10 - 15  diameter - First line defense
3000 - 6000 - Nucleus: variable no. of lobe (no. of - Inflammatory cell
(60 - 70%) lobe increases with age of Neutrophil),
Life time:6 hours to few days Basophilic, Coarse chromatin
[KU 05] - Cytoplasm: Pink, amphophilic
ii. Eosinophil - 10 – 12  diameter - Antiallargic
150 - 400 - Nucleus: Bilobed, basophilic coarse and - Anti-parasitic
(1 - 4%) ropy chromatin
Life time: 8–12 days - Cytoplasm: coarse brick red granules,
acidophilic
iii. Basophil - 12 – 15  diameter - Helps in inflammation
0 – 100 - Nucleus: 's' shaped, basophilic coarse - Immediate hypersensitivity
(0 - 1%) and ropy chromatin reaction
Life time:few hours to a few days - Cytoplasm: Basophilic granules,
vi. Lymphocyte: - Small lymphocyte: 7.5 m diameter, - Humoral and cell mediated
1500 - 2700 scanty cytoplasm, round nucleus, immunity
(25 - 30%) - Large lymphocyte: 10 - 18 m diameter,
Life time:Years for memory clear blue cytoplasm without granules
cells, weeks for all else - Nucleus: round, coarse lumpy chromatin
v. Monocyte: - Largest (10 - 20 ) - Converts to macrophage/
300 - 600 - Nucleus: Kidney shaped. microphage
(5 - 10%) - Cytoplasm: pale blue, purple granules - Stimulate T - cells
Life time:Hours to days - Helps in inflammation
- Stimulate formation of acute
phase protein
III - Pyrogens
Leucopoiesis [KU 06] Regulation of Leucopoiesis:
Pluripotent stem cells
i. Granulopenia or dead granulocytes
ii. Macrophages
Committed stem cells
Release
Colon forming Unit - a. Granulocyte releasing factor (GRF) or
Granulocyte monocyte Leucocytosis inducing factor (LIF)
(CFU - GM) b. Granulopoietin

Myeloblasts Monoblast Inhibit 1. Stimulates bone marrow to cause increased

production and release of stored
Promyelocytes Promonocyte granulocytes in peripheral blood
Negative feedback mechanism

2. Decreases maturation time i.e. stimulates

Myelocytes Monocyte stem cell conversion to granulocytes with
more mitosis
Metamyelocyte
Mature granulocytes (mainly neutrophils
Band form (Juvenile)
Release
Segmented form (mature
Granulocytes i.e. Basophil,
a factor which via
Eosinophil, Neutrophil)

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Variation of WBCs:
Conditions
Neutrophilia or 1. Acute infections
Neutrophilic 2. Metabolic disorders
leukocytosis 3. Injection of foreign proteins
4. Injection of vaccines
5. Poisoning by chemicals and drugs like lead, mercury, camphor, benzene derivatives, etc
6. Poisoning by insect venom
7. After acute hemorrhage
Neutropenia 1. Bone marrow disorders
2. Tuberculosis
3. Typhoid
4. Autoimmune disease
Eosinophilia 1. Allergic conditions like asthma
2. Blood parasitism (malaria, filariasis)
3. Intestinal parasitism
4. Scarlet fever
Eosinopenia 1. Cushing's syndrome
2. Bacterial infections
3. Stress
4. Prolonged administration of drugs like steroids, ACTH and epinephrine
Basophilia 1. Smallpox
2. Chickenpox
3. Polycythemia Vera
Basopenia 1. Urticaria (skin disorder)
III
2. Stress
3. Prolonged exposure to chemotherapy or radiation therapy
Monocytosis 1. Tuberculosis
2. Syphilis
3. Malaria
4. Kala-azar
Monocytopenia Prolonged use of prednisone (immunosuppressant steroid)
Symphocytosis 1. Diphtheria
2. Infectious hepatitis
3. Mumps
4. Malnutrition
5. Rickets
6. Syphilis
7. Thyrotoxicosis
8. Tuberculosis
Lymphocytopenia 1. AIDS
2. Hodgkin's disease (cancer of lymphatic system)
3. Malnutrition
4. Radiation therapy
5. Steroid administration

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2. Thrombocytopenia (Decrease in platelet count)

PLATELETS - Acute infections
 Also called thrombocytes
- Acute leukemia
 1.5 to 4 lakhs/mm3 - Aplastic and pernicious anemia
Thrombopoiesis: - Chickenpox
Haemopoietic stem cells - Smallpox
 - Splenomegaly
Committed stem cell
- Scarlet fever

- Typhoid
Promegakaryoblast
- Tuberculosis

- Purpura
Megakaryoblast
 - Gaucher's disease
Megakaryocyte Activators and Inhibitors of platelets:

Activators platelets Inhibitors of Platelets
Platelet
1. Collagen, which is 1. Nitric oxide
- Formed by pinching off of bit of cytoplasm
exposed during damage 2. Clotting factors: II, IX,
from magakaryocyte
of blood vessels X, XI and XII
Morphology:
2. Von Willebrand factor 3. Prostacyclin
- 2 - 4  in diameter
3. Thromboxane A2 4. Nucleotidases which
- Non - nucleated
4. Platelet- activating breakdown the ADP
- Contains mitochondria, microtubules,
factor
III contractile proteins, and canalicular system
5. Thrombin
Functions:
6. ADP
- Hemostasis (platelet plug formation)
- Vasoconstriction in damaged vessels (liberation 7. Calcium ions
of TxA2 and 5HT) 8. P-selectin: Cell
- Repair of damaged endothelium adhesion molecule
- Clot retraction, Help in blood coagulation secreted from
endothelial cells
- Phagocytosis of Ag - Ab complexes
9. Convulxin; Purified
Variation in platelet count
protein from snake
1. Thrombocytosis (Increase in platelet count):
venom.
- Allergic conditions
- Asphyxia Note:
- Hemorrhage i. Normally platelets are present in an inactive
state in the circulation, unless they become
- Bone fracture
active, there can be no haemostasis.
- Surgical operations ii. Aspirin by inhibiting thromboxane A2 formation
- Splenectomy prevents platelet aggregation. Therefore,
- Rheumatic fever aspirin in low doses is of value in preventing
myocardial infarction and stroke.
- Trauma (wound, injury, or damage caused by
external force)
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BLOOD GROUPS Rh - group

Past Questions: - The Rh-system first described in Rhesus
monkey.
1. Common blood groups and their typing [3] [10 July]
- Consists 6 antigens (i.e. Rh factors): C, D, E, c, d
2. ABO grouping [3] [03 Dec]
and e.
3. Rh-factor and its importance [3] [07 Dec]
- D is potent antigen.
4. Agglutinogens and agglutinins in ABO blood
- Rh – grouping:
groups [3] [05 June]
 Rh +ve with D antigen
Agglutinogens [05]
 Rh -ve without D antigen
- These are antigens present in surface of RBC.
- There is no naturally occurring antibody but
- Antigens are complex of carbohydrates; mainly Anti - D antibody is produced only when Rh -ve
glycosphingolipid and glycoprotein in nature. individual receives D-antigen (i.e. Rh +ve blood)
- Mainly of two types - 'A' and 'B'
Importance:
- Takes part in agglutination reaction. i. Hemolytic transfusion reaction: It occurs when Rh
- Any person may have none antigen (in blood +ve blood is transfused to Rh -ve person who has
group O), may have only one (blood group A or been immunized (or sensitized) by transfusion or
B), or may have both antigen (blood group AB) pregnancy.
Agglutinins [05] ii. Erythroblastosis foetalis
- These are the antibodies to agglutinogens
which are present in blood plasma. BLOOD TRANSFUSION
- These antibodies are produced in body in Past Questions:
sufficient amount after birth, may be due to 1. What is the chemical for storage of blood for
exposure to the respective antigens. transfusion and why? [1+3=4][10 Jan] III
- People with particular agglutinogen lack its 2. Role of blood group in blood transfusion
corresponding agglutinin. [2][03 June]
ABO group [10][03] 3. Erythoblastosis foetalis [4, 3] [08 July, 02 June]
Genotype Blood type Agglutinogen Agglutinin 4. Hazards of mismatched blood transfusion
OO O – Anti-A and [3] [08 Jan, 07 Dec]
Anti - B  Blood collected from one person is given to
OA or AA A A Anti - B another person through a vein is called blood
OB or BB B B Anti - A transfusion.

AB AB A and B – Indications for transfusion:

Conditions Blood products
Landsteiner law:
- In an individual, for particular agglutinogen Haemorrhage Whole blood
present in RBC membrane the corresponding Anaemia Packed cells
agglutinin must be absent in plasma and vice
Burn Plasma, whole blood
versa.
Purpura Platelets or fresh blood
- e.g.; in blood group ‘A’; Agglutinogen: A
Agglutinin: Anti - B Haemophilia AHG or whole blood
i.e. Anti - A is absent. Oedema Albumin

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Hazards of blood transfusion [08][07][02] Clinical picture of Erythroblastosis foetalis:

i. Due to mismatched ii. Due to matched blood - Jaundice (kernicterus can occurs)
blood transfusion transfusion - Anemia
- Child show immature (nucleated) blastic form
Immediate Delayed Immediate Delayed of RBC
- Hemolysis - Jaundice - Pyrogen - Transmission - Hepatosplenomegaly
- Shock reaction disease
- If survive, mental and neurological impairment.
- Renal Failure - Shock - Hemosiderosis
- Circulatory Management of Erythroblastosisfoetalis:
overload - If mother is found to be Rh negative and foetus
- Hyperkalemia is Rh positive, anti D (antibody against D
- Hypocalcemia antigen) should be administered to the mother
at 28th and 34th weeks of gestation, as
Inheritance: prophylactic measure.
- In a pair of chromosome, two genes, (one on
- If Rh-negative mother delivers Rh-positive
each), determine genotype of the individual
baby, then anti D should be administered to
- Genes are of 3 types; 'O', 'A' and 'B'.
the mother within 48 hours of delivery. This
- Possible genotypes: OO, OA, OB, AA, BB and AB.
develops passive immunity and prevents the
- Since, 'O' gene is antigenically unimportant,
antigens in respective genotypes are: formation of Rh antibodies in mother’s blood.
OO  Nil AA  A - If neonate is born with erythroblastosisfoetalis
OA  A BB  B then his/her blood is replaced with Rh -ve
OB  B AB  A and B blood. By the time these transfused Rh -ve
- So, blood groups are: O, A, B and AB. blood is replaced by infants own Rh +ve blood,
III Erythroblastosis foetalis the Anti - D antibody that had come from
[Hemolytic disease of newborn (and foetus)] mother will have been destroyed.
[08, 02]
- It is the disease of fetus and newborn child
HEMOSTASIS
characterized by agglutination and Past Questions:
phagocytosis of fetus red blood cell. 1. Name the clotting factors and describe the
Rh -ve mother (with fetus Rh +ve) mechanism of coagulation. [3+4=7] [05 Dec]
 2. Describe the factors that normally prevent
At time of delivery Rh +ve blood of fetus enters into
intravascular clotting. [4] How does serum differ
maternal circulation
 from plasma? [2] State the functions of plasma
Anti-D antibody develops in mother proteins. [2] [11 July]
 3. Name the clotting factors. Describe briefly the
Mother with Rh +ve fetus during 2nd or 3rd pregnancy mechanism of coagulation [2+4=6] [10 July]
 4. Haemostasis and role of platelets in haemostasis
Anti-D enters fetal circulation through placenta
[3][07 Dec]

Anti-D attack fetal RBCs and causes hemolysis 5. Anti-coagulants [3][06 June]
 6. Mechanism of circulating anticoagulants
Erythroblasts come to circulation [4] [09 July]

7. Hemophilia
Erythroblastosis foetalis
[2,3][08 July 06 Dec, 05 June, 04 June, 03 Dec]

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 It is the process by which bleeding from an injured B. Extrinsic Pathway:

vessel is stopped. It is achieved by 3 processes: - Tissues that are damaged during injury release
- Vasoconstriction tissue thromboplastin (Factor III).
- Platelet plug formation Thromboplastin contains proteins,
- Coagulation/clotting of blood Phospholipid and glycoprotein, which act as
proteolytic enzymes.
Clotting Mechanism
- Glycoprotein and Phospholipid components of
Stage 1: Formation of Prothrombin Activator
thromboplastin convert factor x into activated
- Conversation of prothrombin to thrombin
factor X, in the presence of factor VII.
require Xa complex known as Prothrombin
- Activated factor X reacts with factor V and
activator.
Phospholipid component of tissue
- Two pathways can form Xa complex: Intrinsic &
thromboplastin to form prothrombin activator.
Extrinsic pathway.
This reaction requires the presence of calcium
A. Intrinsic Pathway: ions.
- During the injury, the blood vessel is ruptured.
Note:
Endothelium is damaged and collagen beneath
- Intrinsic pathway starts with activation of factor
the endothelium is exposed.
XII.
- When factor XII (Hageman factor) comes in
- Extrinsic pathway is initiated by tissue
contact with collagen, it is converted into
thromboplastin.
activated factor XII in the presence of
Kallikreinand high molecular weight (HMW) - Activated X forms complex with factor Va,
kinogen. phospholipid & Ca2+ called as prothrombin
activator.
III
- The activated factor XII converts factor XI into
activated factor XI in the presence of HMW - Factors I, II, IV, V, VIII, IX, X, XI, XII, XIII, PL are
kinogen. required for intrinsic Pathway.

- The activated factor XI activates factor X in the - Factors I, II, IV, V, VII, X, PL, TPL are required for
presence of factor IV (Calcium). extrinsic pathway.

- Activated factor IX activates factor X in the - Factors I, II, IV, V, X, PL are common to both
presence of factor VIII and calcium. pathways.

- When platelet comes in contact with collagen
of damaged blood vessel, it gets activated and
releases phospholipids.
- Now the activated factor X reacts with platelet
Phospholipid and factor V to form prothrombin
activator. This needs the presence of calcium
ions.
- Factors I, II, V, VIII, XIII are used up during
coagulation.
- Ionized Ca2+ is essential for coagulation & without
this coagulation cannot occur. Ca2+ is required in
various phases of coagulation. Ca2+ is required in
small amount. Hence, ordinary Ca2+ deficiency
causes tetany instead of coagulation failure.

- Factor V is also activated by positive feedback

effect of thrombin.

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III

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Stage 2: conversion of prothrombin into thrombin: Fibrinolysis/ Fibrinolytic system

- Prothrombin activator that is formed in - Keeps the lumen of blood vessels patent by
intrinsic and extrinsic pathways convert dissolving the clot formed during coagulation
prothrombin into thrombin in the presence of - Carried out by plasmin
calcium (factor IV). Thrombin - thrombomodulin complex on endothelium
- Once formed thrombin initiates the formation 
of more thrombin molecules. The initially Acts as activator of Protein C
formed thrombin activates Factor V. Factor V in

turn accelerates formation of both extrinsic
Activated protein C
and intrinsic prothrombin activator, which
converts prothrombin into thrombin. This
effect of thrombin is called positive feedback
Inactivation of VIII a Inactivates the inhibitors of
effect. and Va tissue plasminogen activator
Stage 3: Conversion of Fibrinogen into fibrin:
- Thrombin converts inactive fibrinogen into
 Activity of tissue
activated fibrinogen due to loss of 2 pairs of
plasminogen activator (TPA)
polypeptides from each fibrinogen molecule. secreted from endothelial
The activated fibrinogen is called Fibrin cells
monomer.
- Fibrin monomer polymerizes with other Plasminogen Plasmin
monomer molecules and form loosely arranged
strands of fibrin.
- Later these loose strands are modified into Fibrin Fibrin
dense and tight fibrin threads by fibrin- Degradation III
Product (FDP)
stabilizing factor (factor XIII) in the presence of
calcium ions. All the tight fibrin threads are - Plasminogen is produced in liver and circulates
aggregated to form a meshwork of stable clot. in blood.
Factors preventing blood clotting in normal Tests for Bleeding Disorders:
blood vessels: i. Clot retraction time:
- Continuous flow of blood
- Gives the idea about platelets functioning as
- Balance between coagulation &
they are responsible for retraction of newly
anticoagulation process
formed clot
- Other factors:
- Platelets attach to adjacent fibrin threads and
a. Healthy endothelium: Smoothness of
draw them together.
endothelium and its negative charge helps
to repel platelets & clotting factors so - The contractile proteins like thrombosthenin,
initiation of coagulation is prevented. actin, myosin, etc. in platelets are responsible
b. Natural anticoagulants like heparin for retraction.
c. Removal of activated clotting factors by - Retraction starts on average by 30 min and
liver serum is squeezed out.
d. Presence of anticoagulation mechanisms - If platelet count is inadequate, time is
(fibrinolytic system) prolonged or no retraction occurs.

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 Physiology

ii. Platelet Count:

Note:
- Decreased platelet count leads to bleeding
CT - Test intrinsic pathway
disorder.
PT - Test extrinsic pathway
- Calculated directly from sample of blood in
counting chamber BT - Test vasospasm and platelet plug formation.

iii. Coagulation time (CT) Hemophilia:

- Time taken by blood to coagulate outside the
body
- Depend on number of factors involved in
coagulation and on container used.
- Normally, capillary tube method is used.
Normal value: 3 to 5 min
- CT prolonged in hemophilia but normal in
purpura.
iv. Bleeding time (BT)
- Time by which bleeding stops from an injury
caused by puncture of sharp needle.
- Normal value: 2 - 4 min
- BT prolonged in purpura but normal in
III hemophilia.
v. Prothrombin Time (PT)
- Time for coagulation of a sample of re-calcified
plasma (plasma + CaCl2) when mixed with
tissue thromboplastin.
- Normal time: 11 to 16 sec (upper limit 25 sec)
- Affected by prothrombin concentration, factor
I, V, VII, and X.
- Hemophilia is a rare bleeding disorder in which
the blood doesn't clot normally.
- 2 types:
 True haemophilia (classical): Lack of factor
VIII
 Pseudohaemophilia: Lack of V, IX or XI
- Treatment is injection of factor VIII or fresh
blood transfusion.
Anti - Coagulant
- Agent when mixed with blood prevents
coagulation (clotting) of blood.
- They prevent deep vein thrombosis, pulmonary
embolism, myocardial infarction and stroke.
- Examples: Heparin, warfarin, acenocoumarol
- Use: In atrial fibrillation, pulmonary embolism,
deep vein thrombosis, venous
thromboembolism, congestive heart failure,
stroke, MI and genetic or acquired
hypercoagulability.

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 Haemopoietic

SPECIAL POINTS FOR MCQs

Factual Data:
1. pH of blood = 7.4 (Range: 7.35 to 7.45)
2. Average blood volume:
- In adult male = about 5 lit.
- In adult female = about 4.5 lit.
3. Average plasma volume in normal adult = 3.5 lit.
4. Specific gravity of blood = 1055 to 1060 at 150c.
5. Water is the major constituent of blood (=91%)
6. Albumin contributes about 80% of the colloidal osmotic tension (COT) of plasma.
7. Albumin: Globulin ratio of plasma = 1.7:1
8. Plasma protein concentration:
- Albumin = 4.7 to 5.7 g/dl.
- Globulin = 1.3 to 2.5 g/dl
- Fibrinogen = 0.2 to 0.4 g/dl
9. Component of protein which contribute to maximum % to total plasma protein is albumin (55%)
10. Blood cells count:
- RBC = 4 - 5.5 million/l [Most abundant blood cells in the human body]
- Reticulocyte count = 0.5 to 1.5% of RBCs
III
- WBC count = 4,000 - 11,000 /mm3.
- WBC differential:
i. Neutrophil = 3000 - 6000 (60 - 70%)
ii. Eosinophil = 150 - 400 (1 - 4%)
iii. Basophil = 0 - 100 (0 - 1%)
iv. Lymphocyte = 1500 - 2700 (25 - 30%)
v. Monocyte = 300 - 6000 (5 - 10%)
- Platelets = 1.5 to 4 lakhs/mm3
11. Blood cells lifespan:
- RBC = 100 - 120 days
- WBC:
i. Neutrophil = 6 hours to few days
ii. Eosinophil = 8 - 12 days
iii. Basophil = few hours to few days
iv. Lymphocyte = up to year (longest living WBC)
v. Monocyte = hours today.
- Platelets = 5 to 9 days

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12. Mean life of RBCs in transfused blood is 60 days.

13. Average volume of RBCs = about 87 3 (range 80 to 94 3)
- If > 94 m3Macrocytosis
- If < 80m3Microcytosis
14. The process of erythropoiesis takes about 7 days.
15. Erythrocyte sedimentation rate (ESR):
- Male = 4mm/hours (average)
- Female = 8 mm/hours (average)
16. Normal hemoglobin (Hb) level:
- Male = 14 to 17 g/dl
- Female = 12 to 16 g/dl
17. RBCs indices:
i. Packed cell volume (PCV) = 45 ml
ii. Haematocrit= 45%
iii. Mean corpuscular volume (MCV) = 873 (80 to 94 3)
iv. Mean corpuscular hemoglobin (MCH) =26 to 34 pg
- > 34pg =Hyperchromic
- < 26pg = Hypochromic
v. Mean corpuscular hemoglobin concentration (MCHC) = 32 to 36 gm/dl
vi. Mean cell diameter (MCD) = 7.5 m
18. Test for bleeding disorders:
III
i. Clot retraction time= 30 min (average)
ii. Coagulation time (CT) = 3 to 5 min.
iii. Bleeding time (BT) = 2 to 4 min
iv. Prothrombin time (PT) = 11 to 16 sec (Upper limit 25 sec)
19. Blood clotting factors:
i. Factor I: Fibrinogen
ii Factor II: Prothrombin.
iii. Factor III: Thromboplastin
iv. Factor IV: Calcium
v. Factor V: Proaccelerin, Labile factor, Accelerator globulin
vi. Factor VI: Do not exist
vii. Factor VII: Proconvertin, SPCA (Serum Prothrombin Conversion Accelerator), Stable factor.
viii. Factor VIII: Antihemophilic factor (AHF), Antihemophilic factor A, Antihemophilic
globulin (AHG)
ix. Factor IX: Plasma thromboplastic component (PTC), Christmas factor, Antihemophilic factor B
x. Factor X: Stuart-Power factor
xi. Factor XI: Plasma thromboplastin antecedent (PTA), Antihemophilic factor c.
xii. Factor XII: Hageman factor, Glass factor.
xiii. Factor XIII: Fibrin-stabilizing factor, Laki-lorand factor.

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20. Hb has 250 times affinity for CO than O2

21. MCHC is never more than 38% because RBC cannot hold hemoglobin beyond its saturation point.
22. Normal myeloid-erythroid ratio in the bone marrow is 3:1.
23. Death usually occurs if more than 350ml of incompatible blood is transfused.

IMPORTANT POINTS:
1. ‘Milieu interieur’ refers to internal environment of the cell.
2. Serum is plasma minus fibrinogen and clotting factors (II, V and VIII).
3. First plasma protein to appear in embryonic life is albumin.
4. Major function of prealbumin is it helps in transport of hormone, thyroxine.
5. Hemoglobin (Hb) iron combines with molecular oxygen rather than ionic oxygen.
6. Glutathione (insoluble protein) act as a reducing agent, thus prevent damage of Hb.
7. RBCs osmotic fragility is increased in spherocytosis, pernicious anemia, megaloblastic anemia;
and decreased in Fe deficiency, sickle cell anemia and thalassemia.
8. Colony stimulating factor (CSF) increases production of all blood cells except lymphocytes.
9. All of the WBCs are normally produced and matured only in bone marrow except lymphocytes (T
and B mature in the thymus and liver respectively).
10. The commonest site of haemopoiesis in a 3 months old fetus is liver.
11. During erythropoiesis, Hb first appears in intermediate normoblast.
12. Most potent stimulus for production of RBCs is decrease in arterial pO2.
13. Erythropoietin is mainly secreted by interstitial cells of peritubular capillaries in the kidney.
14. RBC count is less in young females compared to male of a same age because estrogens depresses III
the erythropoiesis
15. Pituitary disturbances produce anemia due to decreased erythropoietin release.
16. Iron helps in formation of heme in the hemoglobin but not in the maturation of RBCs.
17. Intrinsic factor (Castle’s) with extrinsic factors (VitB12 and folic acid) form haematinic principle
which helps in maturation of RBCs.
18. Deficiency of any factor forming haematinic principle develops megaloblastic anemia.
19. Iron deficiency anemia and thalassemia are characterized by microcytic hypochromic anemia.
[KU 2012 MCQ]
20. In congenital spherocytosis, RBCs are smaller in size (microspherocytes). KU 2012 MCQ]
21. WBC with multilobed nucleus (1-6 lobes) is called polymorphonuclear leucocyte. For e.g.
Neutrophils, eosinophils and basophils.
22. Neutrophil granules are regarded as lysosomes because they contain variety of enzyme that can
digest any type of substance.
23. Neutrophils form first line defense against bacterial infections only and not all infections.
24. The function common to neutrophils, monocyte and macrophage are phagocytosis.
25. Eosinophil granules are rich in lysozymes, histamine & eosinophil chemotactic factor-A but
Histamine content is maximum.

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26. Stress increases the total leucocytes count (TLC) by increasing the neutrophils and not the
eosinophils.
27. Largest WBC in peripheral blood is monocyte; platelet is smallest blood cell.
28. Macrophages are the mature form of monocyte and neutrophils
29. 1st and 2nd line of defense to the body is provided by neutrophils and monocytes respectively.
30. RBC and platelets cannot replicate because they do not have nucleus.
31. Thrombosthenin is a contractile protein like action and myosin present in platelet cytoplasm. It
helps in clot retraction.
32. Platelet derived growth factor (PDGF) stimulates wound healing.
33. Main site for storage of platelets is spleen.
34. Activated platelets stick to each other, called platelets aggregation. This process gets activated by
platelets activating factor & thromboxane A2, and inhibited by prostacyclin and aspirin.
35. The substance released by blood platelets during hemorrhage to produce vasoconstriction is
serotonin.
36. Spontaneous arrest of bleeding by physiological process is called haemostasis (eg. Coagulation)
but homeostasis means mechanisms that control internal environment of a cell.
37. The first important event in haemostasis following severe tissue injury is vascular spasm.
38. Enzyme cascade system involves complex series of reactions in which inactive enzymes are
activated that, in turn, activate other inactive enzymes.
39. The conversion of fibrinogen into fibrin occurs by thrombin.
47. Extrinsic pathway of coagulation is very fast.
III 40. In clotting mechanism via intrinsic and extrinsic pathway, the key reaction is conversion of factor
X to its active form because once Xa is formed clotting takes place within few seconds.
41. In body, heparin is secreted by mast cells and basophils.
42. Vit K helps in the synthesis of clothing factors II, III, IX and X in the liver.
43. Snake bite may cause death by destruction of fibrinogen and stimulation of fibrinolytic system.
44. Ice prevents bleeding by its reflex vasoconstrictor effect and helps to postpone clotting.
45. Parahemophilia, Hemophilia A and Hemophilia B (Christmas disease) are due to deficiency of
factor V, VIII and IX respectively.
46. Differentiation/recognition of blood group is based on Agglutinogen (antigen) not agglutinin
(antibody).
47. Classical ‘ABO’ blood groups agglutinogen first appears in the 6th week of fetal life.
48. Blood group antigens are found in saliva, urine, semen, amniotic fluid, RBCs, Pancreas, kidney,
liver, lungs and testes.
49. Rh +ve individual RBCs contain antigen D and their serum contains no Rh antibody.
50. Cold antibodies and warm antibodies are globulin of IgM and IgG type respectively.
51. In cross-matching before blood transfusion, donor’s RBCs are mixed with recipient plasma.
52. Commonly seen earliest sign of blood transfusion reaction is violent pain in the back or
elsewhere.

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53. A man with blood group A, B or AB cannot be the biological father of a child with an AB blood
type if mother is type O.
54. Addition of glucose to stored blood is to decrease pH because glucose acts by liberating lactic
acid. Glucose also provides a substrate for the metabolism, thus helps in cell survival.
55. 95% of proteins lost per day from vascular system into interstitial fluid is returned to blood via
lymphatics.
56. All types of immune response are fundamentally mediated by lymphoid tissues.
57. Ankyrin and spectrin (proteins on the inner surface of the membrane) are responsible for the
biconcave shape of the red cells. Loss of these proteins results sperocytosis.
58. Erythrocytes sediment due to Rouleaux formation.

59. Iron is absorbed in the upper part of the small intestine.

60. HBA (adult Hb) = α2β2; HBA2 =α22 and HBF [foetal Hb] = α22

61. Glycosylated haemoglobin (HbA1c) is found in diabetes mellitus.

62. HbF has least affinity for 2, 3-Diphosphoglycerate (2,3-DPH) or 2,3-BPH
63. Polycythemia Vera is a disease characterized by high RBC count (upto 8 million) without any
known cause.
64. Haemopoiesis starts form the 3rd week of intra-uterine life, initially in the yolk sac then migrate to
the livers and spleen, then from the 5th month onwards it shifts to the bone marrow and after birth
haemopoiesis is the function of bone marrow only.
65. Erythropoietin is secreted by the hormone producing interstitial connective tissue cells of the
peritubular capillary bed in kidney & also by the perivenous hepatocytes in livers. III
66. Leucocytes are stained by Leishman's stain
67. Most numerous leucocytes =Neutrophils; Largest leucocyte =Monocytes
68. Only neutrophils and monocytes have a common committed stem cell.
69. T-cells are involved in cell mediated immunity (CMI) and are responsible for protection against
viruses, fungi and some bacteria.
70. B cells are involved in humoral immunity and are responsible for protection mostly against
bacterial injections.
71. The helper cells are T4 cells whereas the cytotoxic and suppressor cells are T8 cells.
72. Major histocompatibility complex (MHC) is a group of genes present in human chromosome 6.
73. MHC proteins [also called HLA (Human Leukocyte Antigen)] are never same in two individuals,
except in identical (monozygous) twins.
74. IgG antibody found in plasma, ECF and almost everywhere in the body; can easily pass through
placental barrier and provide passive immunity to the fetus.
75. IgD is the secretory antibody.
76. IgM is also called macroglobulin (largest) and is the antibody to the antigens of RBCs (ABO
system).
77. Cytokines are proteins and behave as autocrine and paracrine agents.
78. Interferons (IFN) are small protein molecules which interferes replication of viruses.

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79. Lymphatics are absent in cartilage, bones, epithelial tissues and brain.
80. The blood group antigens are complex carbohydrates mainly glycosphingolipid and glycoprotein
in nature.
81. The antibodies in the Rh system are of IgG variety
82. Isoantigens are antigens present in some but not in all the members of a species e.g. A-antigen is
present only in group A and group AB individuals.
83. Isoantibodies are antibodies present in some but not in all the members of a species, e.g. in human
only the group B and group O individuals have α agglutinins.
84. Universal donor: Group O, Rh -ve
Universal recipient: Group AB, Rh +ve.
85. The commonly used anticoagulant during the storage of blood is ACD (acid citrate dextrose)
86. Back pain is the most common sign of blood transfusion reaction.
87. Formation of prostacycline from Arachidonic Acid prevents platelet aggregation & hence
coagulation of blood. Prostacycline is produced in intima. This mechanism limits the platelet
activation & takes place simultaneously.
88. Critical count of platelet is a count below which bleeding will occur.
89. Key step of coagulation is conversion of fibrinogen into fibrin monomer after removal of 2 parts
of polypeptides (1 pair of fibrinopeptide A & 1 pair of fibrinopeptide B)
90. Stabilization is the process by which the initially formed fibrin threads are made stable by
activated factor XIII & Ca++.
91. Ionized Ca2+ is essential for coagulation & without this coagulation cannot occur. Ca2+ is required
in small amount. Hence ordinary Ca2+ deficiency causes tetany instead of coagulation failure.
III
92. Thrombomodulin acts as plasminogen to form plasmin which breaks down fibrin thread of clot &
the clot is dissolved.
93. Female usually does not suffer from hemophilia because of presence of another healthy X
chromosome unlike male who have only one X chromosome.

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