BLOOD

It is a specialized connective tissue Represents 8 % of the total body wt. Components: 1) Formed elements: cellular portion (45%) 2) Plasma: fluid portion (55%) 1) Formed elements: Red blood cells (RBCs) (erythrocytes) White blood cells (WBCs) (leucocytes) divided into: 1) Granulocytes: (neutrophils, eosinophils & basophils) 2)Agranulocytes;( monocytes & lymphocytes) Platelets (thrombocytes) Adults have 4-6 litres of blood pH --------------- 7.35---- 7.45

FUNCTIONS OF BLOOD

1) TRANSPORT. Carries o2 and CO2 b/w lungs and other organs carries nutrients from GIT & storage depots to other organs Carries waste products to liver and kidney for detoxification or removal Carries hormones from endocrine glands to target tissue Carries heat to skin for removal, thus regulates body temp.

2) PROTECTION Plays several role in inflammation. WBCs destroy micro organism & cancer cells. Antibody or other proteins destroy pathogens Platelets initiates clotting and minimize blood loss 3) REGULATION Transfers water to and from the tissues , helps stabilize water balance, buffers acids and bases thus stabilize pH

PLASMA: (straw colored) it is the fluid portion of the blood. It is a complex mixture of proteins, enzymes, nutrients, wastes products, hormones and gases Contains 91.5% of water & 8.5 % of solutes, most of which are proteins (plasma proteins). Liver synthesize most of the plasma proteins which includes albumin (54%), globulins (38%)& fibrinogen (7%) Gamma globulins or immunoglobulin's (antibodies) are produced by cells in response to foreign invaders (virus , bacteria) and destroys them

FUNCTIONS OF PLASMA PROTEINS Exert colloid osmotic pressure , which helps maintain water balance b/w blood & tissues and regulates blood volume Albumins: functions as transport protein for several steroid hormones & fatty acids Globulins: role in killing bacteria & viruses Fibrinogen: plays an essential role in blood clotting.

 RED BLOOD CELLS (ERYTHROCYTES) They are biconcave disc shaped non- nucleated cells with no mitochondria Have a diameter of 7.8 micrometers. Thickness -------- 2 micrometers They can change their shape as they squeeze through the capillaries. Normal value is 4.8 --- 5.4 millions /mm3 RBC contains hemoglobin which is used for the transportation of gases. Act as a buffer. Provides constant amount of O2 to the tissues Life span - ------------ 120 days Biconcave disc shape provide a larger surface area for

diffusion of O2 across the membrane

GENESIS OF R.B.C. Early few weeks of embryo ----- nucleated RBCs (yolk sac) In mid trimester ------ liver (mainly) partly by spleen & lymph nodes In last trimester & after birth --------- bone marrow. Up to 5 yrs -------------- bone marrow of all bones by the age of 20 -------- marrow cavities of long bones becomes inactive except upper end of humerus & Femur Beyond 20 --------------- membranous bones Role of spleen. Filter that removes aged or abnormal RBCs

P.H.S.C. C.F.U.S C.F.U.B.E Pro- Erythroblast (no Hb, size large, nucleus pre. Contain nucleoli) Basophil Erythroblast (Hb appear, takes basic dye nucleoli absent , size smaller)

Polychromatic erythroblast (size small, nucleus small, stain with both acidic & basic dye) Orthochromatic erythroblast (nucleus shrinks & than lost) Reiculocyte (no nucleus, some mitochondria & ribosome stays in bone marrow for 2-3 days , release in blood where it stays for 24 hrs , here it loses its mitochondria & assume mature RBC . count is 1%)

Erythrocyte

.Regulation of Erythropoesis: Any condition that decreases the O2 transport to the tissue in turn increases the erythropoesis. For e.g. A) hemorrhage B) high altitude C) lung diseases D) heart diseases.

Role of erythropoietin: A hormone with a MW of 34,000 is released mainly by the kidney & partly by the liver in response to hypoxia & increases the RBC production . Level is decreased in chronic renal disease. Role Vitamin B12 & folic acid: Both of these are used for the final maturation of RBC They are essential for DNA synthesis & in their absence there is failure of nuclear maturation and division The peripheral film shows macrocytes (large size RBC) RBC lost their biconcave disc shaped and are more fragile

HEMOGLOBIN It is a red , oxygen carrying pigment in the RBCs It has a MW of 64,450. It is a globular protein with 4 sub units Each units contains heme combines with a polypeptide chain. Heme is an iron containing compound Polypeptide referred to globin portion of the HB There are two pairs of polypeptide chain in Hb Adult Hb (Hb A) --------- 2 , 2 chains Hb A2 (2.5%) --------- 2 , 2. Hb F -------- 2 , 2. HbA1c (Hb A derivative) represent glycated Hb has a glucose attatch to Beta chain

STEPS IN SYNTHESIS OF Hb

2 succinyl CoA + 2 glycine

4 pyrrole
protoporphyrin IX + Fe Heme + polypeptide chain

2 , 2 chains

Pyrrole protoporphyrin IX heme Hb chain hemoglobin A

ANEMIA Reduced amount of Hb below normal with respect to age & sex is known as anemia

CLASSIFICATION 1) Morphological classification 2) Pathophysiological classification

1) MORPHOLOGICAL CLASSIFICATION: It is based in size shape & color of RBC A) Macrocytic Normochromic anemia: Contains large shaped cells with normal Hb concentration. E.g. megaloblastic anemia or Pernicious anemia.
B) Microcytic Hypochromic anemia:

It produced small , abnormal RBCs with reduced Hb conc. e.g. are iron def. anemia & thalassemia
3) Normocytic Normochromic anemia:

In this RBCs are of normal size with norma Hb content but they are insfficient in number.
4) aplastic anemia

2) Pathophysiological classification:
A) Blood Loss:

acute: trauma ii) Chronic: ulcer

i)

normocytic normochromic microcytic hypochromic

B) Hemolytic anemia: i) RBC membrane defect: e.g heriditary spherocytosis A protein spectrin is deficient. ii) Enzyme defect: G6PD deficiency (punched out holes) ii) Hemoglobin defect: e.g. thallassemia, sickle cell anemia.

.3) autoimmune : i) Drug induced: ii) Erythroblastosis fetalis

Effect of anemia on the body Viscosity o the blood is decreased. This results in decrease in peripheral resistance to the blood flow & causes increase in blood flow to the heart Hypoxia results from decrease in hemoglobin causes an increase in blood flow to the heart All this results in increase in cardiac out put. If a person starts exercising the condition even becomes more severe.

Polycythemia it is a condition in which the qty of RBCs are increased. It is of two types 1) primary Polycythemia: Also called Polycythemia rubra Vera. Chronic disease in which the bone marrow becomes hyper excitable results in increased formation of RBCs Males are mostly affected The pluripotent cells becomes hyper responsive to erythropoietin & results in increased formation of RBCs. Blood viscosity is increased.

Patient usually complains of headache, blackout, epistaxis &

itching. Tendency of blood clotting is increased Management : Therapeutic venesection or taking out some blood (500 ml) from patient gives temporary relief. Secondary Polycythemia: It is secondary to other causes for e.g. Increased erythropoietin production secondary to hypoxia. High altitude Smoking Congenital heart disease. Lung diseases

Iron metabolism Total qty of iron in the body is 4-5 gms. 65% is in the form of Hb. 4% is in the form of myoglobin. 1% is in the form of various heme compounds. 0.1% is present in combination with protein tranferrin in the plasma. 15-30 % is stored mainly in liver in the form of ferritin

Transport & storage of iron After its absorption in blood it loosley combines with a plasma protein known as apotransferrin to form transferrin. excess iron deposits mainly in liver & less in reticuloendothelial cells of bone marrow . In the cell cytoplasm iron combines with a protein apoferritin to form fereritn This is the stored form of iron small qty of iron is also stores in the insoluble form as hemosiderin. This occurs when ferritin stores are saturated. When the qty of iron in the body is decreased , iron is removed from ferritin (stored form) , released in plasma , where it binds with transferrin & delivers to that part of the body where it is needed. The transferrin molecule binds with cell membrane of the erythroblast , where it is endocytosed & delivers iron directly to the mitochondria for heme synthesis.

ABSORPTION OF IRON FROM G.I.T. Iron is absorbed from all part of intestine. Liver secrete apotransferrin in the bile which comes in the intestine. Here it combines with iron as well as with hemoglobin & myoglobin present in meat. This combination is known as transferrin. This complex binds with the receptor present over the intestinal epithelial cell. Thus by the process of pinocytosis transferrin carrying its iron is absorbed in the blood.

In man
In women

Daily iron loss 0.6 mg. 0.6 mg + 1.3 mg/day

FATE OF R.B.Cs As the mature RBCs do not contain any nucleus, E.R. or mitochondria, it contains cytoplasmic enzymes that performs the following functions; 1) metabolism of glucose for ATP synthesis. 2) stabilizes the cell membrane 3)keeps the iron in Fe++ (ferrous) form rather than the Fe+++ (ferric) form. 4) prevents the oxidation of proteins in the red cells. Once the RBC membrane becomes fragile, the red cell ruptures as it passes through the small capillaries or it passes through the spleen.

When the red cells becomes destroyed , it releases

hemoglobin which is phagocytized by the macrophage of spleen , liver & bone marrow. the macrophage releases iron from Hb which is taken up by the transferrin , which transports it to the liver for erythropoesis or stored in the cell in the form of ferritin Fate of porphyrin Protorphyrin biliverdin bilirubin

liver
conjugated bilirubin

excreted in bile