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PHYSIOLOGY - KEY NOTES

VERSION-1


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PHYSIOLOGY

INDEX

Blood and its formed elements

Cardiovascular system, heart

Gastrointestinal tract

Respiratory system

Nephrology

Endocrinology

The central nervous system


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RED BLOOD CELLS:

1. most abundant cells of the blood

2. contain a large quantity of carbonic anhydrase, an enzyme

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 biconcavi ty

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”

BLOOD

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PRODUCTION OF RED BLOOD CELLS

1. erythropoeisis starts in 3rd

week of i ntrauterine life

2. Site of RBC synthesis

a. In the 3rd

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).

[email protected] Mb: 099451 06051

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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

1. sinusoids ( capillaries with large diameter)

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

[email protected]

Mb: 099451 06051

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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

fruits, and meats (especially liver). However, it is easily

destroyed during cooking.

d. Disease called sprue: abnormal absorption of Vit B12 and

folic acid.

Cases of pernicious anemia develop neurologi cal symptoms

but not the cases of folate deficience: both cause megaloblastic

anemia (because Vit B12 deficiency causes demyelination of nerves)


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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 +

anticonaglant is centrifuged, the

volume of the packed cell is PCV

45 per 100 ml

Ie 45%

Mean corpuscular volume (MCV)

=

90 cub µ

Mean corpuscular Hb : Hb in

each RBC

RBC count in million/

cmm

=

Hb in gm / liter of

blood

30 pg


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Mean corpuscular Hb

concentration: amount of Hb

present on 100 ml of RBC

33.3 gm/100 ml of cells


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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, betachains, gamma chains, and delta chains.


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Hb Type formula

hemoglobin in the

adult human(98%)

HbA two alpha chains and

two beta chains

hemoglobin in the

adult human(2%)

HbA2 Two alpha two delta

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


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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 affinit y 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

plasma with a beta globulin, apotransferrin, to form transferrin,

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


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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 reproducingage.

3. Iron overload : Bronze diabetes = excess hemosiderin in the body


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FATE OF HB:


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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


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Thalassemia : (α or β chain defect ): refer O Path for details

Hb D Punjab : mild hemolytic anemia in 2% Punjab population

AMEMIAS:

Iron deficiency anemia: microcytic hypochromic an.

Vit B 12 and folate deficiency : Megaloblstic anemia, macrocytic

hemolytic anemia: Normocytic , increased bilu rubin

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

blood.

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


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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


notes

Exercise: Diagram WBCs


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functions:

1. immunity and protection

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


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c. fibrinogen: 0.3 gms/dld. 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

1. Agglut inogens (ant igen) that react with specifi agglutinins

(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 immunog lobulins

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


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Appl ied:

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

main Rhesus antigens (C, c, D, E and e) as well as the many

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:

Antibodies that react best at temperature between 5-20o 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.


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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

are destroyed but the recipient erythrocytes are not harmed

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 cont ains only one day reserve for the platelets

so humans prone to develop thrombopenia


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d. Life span : 7 to 12 days

Platelet

granules

contents

Alpha

granules

• Fibronectin

• 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

granules

• ATP, ADP

• serotonin

Glycogen

granules


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1. tubules of platelet :

a. open tubules (Ca++

from ECF can enter platelets

from here when needed)

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


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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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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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