Sample chapter from Physiology keynotes .. Aim MDS

2. PHYSIOLOGY - KEY NOTES
VERSION-1

3. PHYSIOLOGY
INDEX
Blood and its formed elements
Cardiovascular system, heart
Gastrointestinal tract
Respiratory system
Nephrology
Endocrinology
The central nervous system

4. BLOOD
RED BLOOD CELLS:
1. most abundant cells of the blood Discussion notes/ my
2. contain a large quantity of carbonic anhydrase, an enzyme notes
that catalyzes the reversible reaction between carbon dioxide
(CO2) and water to form carbonic acid (H2CO3)
3. is an acid-base buffer
diameter of about 7.8 micrometers and a thickness
of 2.5 micrometers at the thickest point and 1 micrometer or
less in the center.
4. RBCs have no nucleus and no mitochondria, ribosomes, ER
and centriole.
Since it does not contain mitochondria tricarboxylic acid
cycle of the Krebs does not operate within it
5. cell membrane of RBC contains proteins
a. Glycophorins (that extend through and through the
membrane ) eg : blood group antigen
b. Others like spectrin and actin are applied on the inner
side of the cell membrane
6. RBC is biconcave due to a contractile protein “SPECTRIN”
7. Life span of RBC: 120 days. Number of RBCs dying daily is
about 3.0 X 109 / kg body weight of the person.
Advantage of biconcavity
1. increase in the surface area for the absorption of oxygen
2. ,because of the biconcavity, the erythrocyte can squeeze
through the vessels.
The disease where bico'ncavity of RBCs is lost is K/as
“sperocytosis.” Or “elliptocytosis”

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PRODUCTION OF RED BLOOD CELLS
rd
1. erythropoeisis starts in 3 week of intrauterine life Discussion notes/ my
2. Site of RBC synthesis notes
rd
a. In the 3 wk to 3rd mnth of embryonic life, primitive,
nucleated red blood cells are produced in the yolk
sac. (Intravascular erythropoiesis)
b. During the3rd mnth to 5th of gestation, the liver is the
main organ , but are also produced in the spleen and
lymph nodes.(hepatic phase)
c. Then, during the last month or so of gestation and
after birth, red blood cells are produced exclusively in
the red bone marrow.(myeloid phase)
Extramedullary erythropoeisis: when there is necessity even yellow
bone marrow, liver and spleen start erythropoisis. (Thymus never
forms blood cells).
Proerythroblast : pronormoblast
= first in erythroid series
Basophil erythroblast: Early
normoblast
Polychromatophillic erythroblast:
intermediate normoblast (Hb
appears)
Late normoblast : orthochromatic
erythroblast (pyknotic nucleus)
Reticulocyte (nucleus extruded)
Note : in earlier phase cytoplasm
contains abundant RNA hence
stains basophilic and with
maturation Hb increases which is
acidophilic.
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HISTOLOGY OF THE BONE MARROW:
BM consists of Discussion notes/ my
1. sinusoids ( capillaries with large diameter) notes
2. adventitious cell (that later covert into fat cells)
3. myeloid cells (that form the blood cells)
Normal fat cell : blood cell ratio of the bone marrow is 1:1
The myeloid: erythroid ratio of the normal bone marrow is 3:1
REGULATION OF RED BLOOD CELL PRODUCTION:
1. Tissue Oxygenation
2. erythropoietin, a glycoprotein with a molecular weight of about
34,000.produced in Kidney (90%) and rest in liver (10%)
(note : When both kidneys are removed from a person or when the
kidneys are destroyed by renal disease, the person invariably becomes
very anemic)
3. Maturation of Red Blood Cells—Requirement for Vitamin B12
(Cyanocobalamin) and Folic Acid
a. Both of these are essential for the synthesis of DNA,
b. the erythroblastic cells of the bone marrow, in addition to
failing to proliferate rapidly, produce mainly larger than
normal red cells called macrocytes,
Pernicious Anemia.In pernicious anemia basic defect is in
gastric atrophy thus parietal cells fail to produce Intrinsic factor (that
binds Vit B12 i.e. extrinsic factor and make the latter available for
absorption.) Lack of intrinsic factor, therefore, causes diminished
availability of vitamin B12
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c. Deficiency of Folic Acid (Pteroylglutamic Acid). Folic
acid is a normal constituent of green vegetables, some Discussion notes/ my
fruits, and meats (especially liver). However, it is easily notes
destroyed during cooking.
d. Disease called sprue: abnormal absorption of Vit B12 and
folic acid.
Cases of pernicious anemia develop neurological symptoms
but not the cases of folate deficience: both cause megaloblastic
anemia (because Vit B12 deficiency causes demyelination of nerves)
4. Vitamin B6 and Vitamin C:
a. Vitamin C is concerned with the absorption of iron.
5. Iron:
a. Concerned with the formation of hemoglobin
RED CELL INDICES:
RBC count Adult men: 5.5 million/ cu mm
Females: 4.8 million/ cu mm
Hb concentration 15 gm / 100 ml of blood
Packed cell volume : blood + 45 per 100 ml
anticonaglant is centrifuged, the Ie 45%
volume of the packed cell is PCV
Mean corpuscular volume (MCV) 90 cub µ
=
Mean corpuscular Hb : Hb in 30 pg
each RBC
Hb in gm / liter of
blood
=
RBC count in million/
cmm
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Mean corpuscular Hb 33.3 gm/100 ml of cells Discussion notes/ my
concentration: amount of Hb notes
present on 100 ml of RBC
The intensity of erythropoiesis can be judged by the count of the
% of reticulocyte in the blood.
Count > 3 % indicate increased erythropoiesis
Count < 0.5 % indicate less than normal erythropoiesis .
FORMATION OF HEMOGLOBIN
1. Begins in the proerythroblasts and continues even into the
reticulocyte stage of the red blood cells
2. Four pyrroles combine to form protoporphyrin, which then
combines with iron to form the heme molecule.
3. Finally, each heme molecule combines with a long polypeptide
chain, a globin synthesized by ribosomes, forming a subunit of
hemoglobin called a hemoglobin chain
4. The different types of chains are designated alpha chains, beta
chains, gamma chains, and delta chains.
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Hb Type formula Discussion notes/ my
hemoglobin in the HbA two alpha chains and notes
adult human(98%) two beta chains
hemoglobin in the HbA2 Two alpha two delta
adult human(2%) chains
Fetal Hb HbF Two alpha two gamma
chains
Sickle Hb HbS amino acid valine is
substituted for
glutamic acid at one
point in each of the two
beta chains
5. Hemoglobin A has a molecular weight of 64,458. (~ 65-67 KD)
6. Four molecules of oxygen (or eight oxygen atoms) that can be
transported by each hemoglobin molecule.
In sickle cell anemia
the amino acid valine is substituted for glutamic acid at one point in
each of the two beta chains. When this type of hemoglobin (Hb S) is
exposed to low oxygen
it forms elongated crystals (tactoids) inside the red blood cells
resulting in the sickling of the RBC.t hese sicled RBCs rupture when
they pass through the narrow capillaries.
7. Hb has 250 times more affinity to CO than O2
IRON METABOLISM
1. The total quantity of iron in the body averages 4 to 5 grams, about
65 per cent of which is in the form of hemoglobin.
2. Iron in absorbed in ferrous state where as it is present in food in
ferric state;
ascorbic acid (vit c ) being a reducing agent
converts ferric iron to ferrous iron
3. it is absorbed in the upper part of the intestine.
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4. When iron is absorbed, it immediately combines in the blood Discussion notes/ my
plasma with a beta globulin, apotransferrin, to form transferrin, notes
which is then transported in the plasma to the bone marrow for the
formation of RBCs and to tissues for formation of other iron
containing compounds.
5. After the death of RBC , iron is extracted and retained as “Ferritin”
(ferric state) in Reticuloendothelial system. (thus ferritin comes
from dead RBCs and not from food)
6. Ferritin is stored within the case of a protein apoferritin.
7. when iron is excessive it forms hemosiderin (part of protein casing
is lost)
8. iron in Hb is in ferrous state, …. And even after taking up the
oxygen remains in ferrous state. The enzyme that prevents the
oxidation is methemoglobin reductase with NADH
Methemoglobinemia: iron of Hb is oxidized to ferric form and
oxygen cannot release itself from such Hb
Iron requirement:
1. iron is deposited in fetal body in the last phase of intrauterine life
…hence premature babies are susceptible to iron deficiency
2. Iron req in adult as low as 1 mg increases in women of reproducing
age.
3. Iron overload : Bronze diabetes = excess hemosiderin in the body
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FATE OF HB:
Discussion notes/ my
notes
normal bilurubin Conc : 0.5 to 1 mg/dl
Glucoronyl transferase catalyses conjugation: when absent :
Criggler najjar syndrome
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porphyria, porphyrinuria: defective heam synthesis
Thalassemia : (α or β chain defect ): refer O Path for details Discussion notes/ my
Hb D Punjab : mild hemolytic anemia in 2% Punjab population notes
AMEMIAS:
Iron deficiency anemia: microcytic hypochromic an.
Vit B 12 and folate deficiency : Megaloblstic anemia, macrocytic
hemolytic anemia: Normocytic , increased bilurubin
Aplastic anemia : reticulocyte count drops to “Zero”
polycythemia :increase RBC count
a. primary : Polycythemia vera, unknown eitiology
(erythropoietin concentration in low)
b. secondary : disease(eg. Emphysema) increased
erythropoietin increased RBC
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THE LEUCOCYTES:
1. about 7000 (4500- 11000) white blood cells per microliter of Discussion notes/ my
blood. notes
2. normal percentages of the different types (differential count)
based on Romanowskis stain.
Stain components: Azure B= basic that combines
with acidic material and Eosin Y =acidic that
combines with basic
3. Variant of Romanowskis stain: Wright stain , Leishman stain
, Giemsa stain , Jenners stain
Exercise: Diagram WBCs
Neutrophil
neutrophil lobes: several: young neutrophil less lobes number
Arneth count: ratio between different lobed nutrophils
More young cells : shift to left and older cells shift to right
Shift to left : infection
Shift to right megaloblastic anemia
Eosinophils:
Bi-lobed nucleus, coarse granules
Basophil
S shaped nucleus, coarse basophilic granules
Monocytes:
Largest WBC, ovoid nucleus very often indented (horse shoe
shape)
Non granulocyte but has fine granules
lymphocyte : small and large
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functions: Discussion notes/ my
1. immunity and protection notes
2. neutophils : first line of defence; also called microphage
3. Monocytes: second line of defence
4. Eosinophils : antiparasitic, heve little or no activity against
bacteria
5. applied physio:
leucocytosis: >11,000 WBCs/cu mm of blood
i. neutrophilic leucocytosis : acute bacterial
infection
ii. eosinophilic leucocytosis: parasitic infection
THE PLASMA PROTEINS:
1. Blood = plasma + formed elements
2. Serum= plasma – fibrinogen
3. plasma contains 6-8 gms protiens/100ml
4. the proteins of plasma:
a. albumin: 4 gms/dl
b. globulin: 2.5 gms/dl
Thus in health albumin: glubulin ratio is 1.7
c. fibrinogen: 0.3 gms/dl
d. prothrombin 0.03 gms/dl
5. albumin maintains colloidal osmotic tension of the blood Thus
hypoalbuminaemia leads to retension of water in the tissues:
edema
6. Oncofetal antigens: some proteins are synthesized only in fetus
and their levels drop later, if in the post natal life person develops
cancer these proteins appear again and hence called as Tumor
markers:
a. eg: a. Carcinoembryonic antigen
1. b. Alpha fetoprotein
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BLOOD GROUPS
RBC contain Discussion notes/ my
1. Agglutinogens (antigen) that react with specifi agglutinins notes
(antibodies) in plasma
a. The agglutinogen are present on the surface of the
RBCs and are chemically glycoproteins.
b. the agglutinins are plasma globulins and are either
IgM or IgA type of immunoglobulins
2. there are various blood grouping systems, the important ones are
ABO system, Lewis, Duffie, Lutheran and so on.
3. The blood grouping systems: The ABO blood group system is
widely credited to have been discovered by the Austrian scientist
Karl Landsteiner
Applied:
1. ABO blood group incompatibilities between the mother and
child does not usually cause hemolytic disease of the newborn
(HDN) because antibodies to the ABO blood groups are
usually of the IgM type, which do not cross the placenta;
however, in an O-type mother, IgG ABO antibodies are
produced and the baby can develop ABO hemolytic disease
of the newborn.
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Rh Factor:
1. The term Rhesus (Rh) blood group system refers to the 5 Discussion notes/ my
main Rhesus antigens (C, c, D, E and e) as well as the many notes
other less frequent Rhesus antigens. The terms Rhesus
factor and Rh factor are equivalent and refer to the Rh D
antigen only.
2. Individuals either have, or do not have, the Rhesus factor (or
Rh D antigen) on the surface of their red blood cells. This is
usually indicated by 'RhD positive' (does have the RhD
antigen) or 'RhD negative' (does not have the antigen)
suffix to the ABO blood type
Some facts about blood group antigens and antibodies:
Anti A and anti B antibodies are produced by the body without
being challenged by the antigens, such antibodies are called as
naturally occurring antibodies.
Secondly as seen earlier anti- A is present in individuals which do
not have A antigen in their RBC, such antibody which cab react
with the antigen not present in a person in whom these
antibodies are present is called alloantibody or iso antibody.
On the other han Rh antibody develops only after the exposure to
antigen, thus they are immune antibodies.
Cold and warm antibodies:
o
Antibodies that react best at temperature between 5-20 are cold
antibodies and those which react best at human body
temperature are warm antibodies.
Most of the blood group antibodies are of IgM variety which are
cold antibodies thus they do not react at body temperature.
The well known exceptions are Anti-A and anti- B which,
inspite of being IgM type are warm antiboidies
While Rh-antibodies are initially IgM type and later they
switch to IgG type (can cross the placenta), and are warm
antibodies.
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In mismatched blood transfusion only the donor’s erythrocytes Discussion notes/ my
are destroyed but the recipient erythrocytes are not harmed notes
because during transfusion the donor’s antibodies get mixed with
recipient and get diluted thus ineffective.
PLATELET, HEMOSTASIS AND COAGULATION:
1. normal platelet count : 1,50,000 to 4,00,000/cmm(μl)
2. critical count of platelet: 40,000 below which hemorrhagic
manifestation occurs
3. morphology:
a. non nucleated (no DNA or RNA)
b. disc like when inactive and on activation become
spherical
c. synthesized in RBM from megakaryocytes, (a
single megakaryosite can give rise to 1000
platelets)
Bone marrow contains only one day reserve for the platelets
so humans prone to develop thrombopenia
d. Life span : 7 to 12 days
Platelet contents
granules
Alpha • Fibronectin
granules • Platelet factor 4
• Platelet growth factor
• Von willibrand factor vWF derived from two sources
vascular endothelium and platelets
• Thrombospondin:Thrombospondin acts as bridge
between platelets and between platelet and
fibrinogen.
Dense • ATP, ADP
granules • serotonin
Glycogen
granules
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1. tubules of platelet :
++
a. open tubules (Ca from ECF can enter platelets Discussion notes/ my
from here when needed) notes
++
b. dense tubules (store Ca ions)
2. two contractile elements
a. actin
b. myosin
3. platelet membrane:
a. outer glycocalyx
b. inner lipoprotein
4. Genesis: derived from Megakaryocytes
HEMOSTASIS AND COAGULATION
Clotting : three stages
a. Stage I: formation of prothrombin activator
b. Stage II: prothrombin activator converts prothrombin
to thrombin
c. Stage III: thrombin converts fibrinogen to fibrin
Formation of prothrombin activator: 2 major pathways:
a. The intrinsic pathway: triggered by activation of
Hageman factor (XII); Factor XII could be activated
even by contact with glass henceaka Glass contact
factor
b. The extrinsic pathway: triggered by release of tissue
factor (TF)
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Discussion notes/ my
notes
Vitamin K is necessary for liver formation of five of the
important clotting factors:
1. prothrombin,
2. Factor VII,
3. FactorIX,
4. Factor X,
5. and protein C.
Liver synthesizes: Factor V, VII, IX, X, prothrombin,
fibrinogen and anticoagulants thrombin, antithrombin III and
protein C
Disseminated Intravascular Coagulation: results from the
presence of large amounts of traumatized or dying tissue in the
body that releases great quantities of tissue factor into the
blood.usually in septicaemia (due to endotoxins);
d. These patients also show increased bleeding
tendency as lots of coagulation factors are used up
THE TESTS OF COAGULATION:
The partial thromboplastin time (PTT) or activated partial
thromboplastin time (aPTT or APTT) :
is a performance indicator measuring the efficacy of both the
"intrinsic" (now referred to as the contact activation pathway)
and the common coagulation pathways Deficiencies of factors
VIII, IX, XI and XII and rarely von Willebrand factor (if causing
a low factor VIII level) may lead to a prolonged aPTT
prothrombin time (PT) which measures the extrinsic pathway.
The reference range for prothrombin time is usually around
12–15 seconds; the normal range for the INR is 0.8–1.2. PT
measures factors II, V, VII, X and fibrinogen.
Clotting Time: collect blood in a chemically clean glass test
tube and then to tip the tube back and forth about every 30
seconds until the blood has clotted. By this method, the
normal clotting time is 6 to 10 minutes.
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