Physiology of Blood PDF

Physiology of blood By Dr. Mohammad Ghalwash  Blood Blood is the part of ECF that circulates within the CVS. The total blood volume is about 8 % 0f body weight The blood volume is about 80 ml/ Kg, so in 70 Kg person is about 5600 ml. Infant 5 k...

Physiology of blood By Dr. Mohammad Ghalwash  Blood Blood is the part of ECF that circulates within the CVS. The total blood volume is about 8 % 0f body weight The blood volume is about 80 ml/ Kg, so in 70 Kg person is about 5600 ml. Infant 5 kg about 400 ml.  General function of the blood 1) The transport medium in the body: – Blood transport many substances among different organs as: glucose, O2, CO2, hormones and others. 2) Homeostatic function: – Keeping the internal environment constant that is achieved by continuous exchange of substances between interstitial fluid and organs. 3) Defensive function (Immunity): – The blood protect the body against invasion by microorganisms through cellular and humoral immunity. 4) Haemostatic function – Stoppage of bleeding by platelet plug and blood clot formation. Blood composition  Blood composition Blood Cells Plasma 45 % of blood volume 55 % of blood volume RBCs WBCs Platelets Water Organic Inorganic 4.5 – 5 x 4 – 11 x 150 – 400 x 90% 9.1% 0.9% 106/mm3 103/mm3 103/mm3  Plasma proteins Normal concentration of PP is 6 – 8 gm /dl, PP include: – (1) Albumin (3.5 – 5 gm/ dl) – (2) Globulin (2.4 – 2.7 gm/ dl) – (3) Fibrinogen (0.2 – 0.4 gm/ dl) – (4) Other specific types of plasma proteins  Sites of formation of PP 1) Liver : – Synthesize most of PP: as Albumin, fibrinogen, prothrombin and most of globulin –Except gamma globulin. 2) B Lymphocyte & Plasma cells in lymphatic tissues: – synthesize gamma globulin fraction of PP (immunoglobulins)  Functions of plasma proteins I) General functions of PP 1. Blood viscosity: especially fibrinogen. 2. Regulation of blood volume and tissue fluid formation: (Plasma colloid osmotic pressure) (especially albumin). 3. Buffering action of PP: responsible for about 15% of the buffering power of the blood, prevent great changes in the blood pH. 4. CO2 carriage: CO2 combine with the amino groups of PP forming carbamino compounds. II) Specific functions of PP 1. Carrier function of PP 2. Blood clotting & fibrinolysis: Most of blood clotting factors & fibrinolytic system are PP 3. Immunity (immunoglobulin): protect the body against infections.  General functions of PP 1) Blood viscosity – The whole blood is 3 times as viscid as water due to RBCs, and Plasma proteins. – Plasma is about 1.5 that of water due to Plasma proteins: especially fibrinogen due to its (large MW and elongated shape molecule). – Blood viscosity is one of the causes that help to maintain ABP.  Carrier functions of PP Def: Transport substances from site of synthesis or absorption to the site of action or storage. Significance 1) Make water insoluble substances (lipids, steroid hormones) miscible with water to be circulated with plasma. 2) Prevent rapid loss of the carried substances in urine. Examples: 1) Albumin: carrier for (thyroid & steroid H, fatty acids, aa, bilirubin, vit, many drugs). 2) Globulin: carry iron (Fe+) Transferrin , copper (Cu) Ceruloplasmin, vit B12 Transcobalamin and Steroid hormones (cortisol, sex hormones) Red blood cells RBCs  Red blood cells RBCs Named red blood corpuscles as it not a true cell as it do not contain nuclei and other cell organells as ER & mitochonderia Normal RBCs count: – Adult male : 5 - 5.5 million/ mm3 – Adult female : 4.5 – 5 million/ mm3 – Being higher in: – new born 6 – 8 million/ mm3 – person living at high altitude  RBCs size and shape: Normal RBCs are circular and biconcave discs Diameter 7.8 micron Thickness 2.5 micron Volume 90 cubic micron Significance of RBCs shape 1. Give Larger surface area RBCs life span about 120 days  Structure of RBCs 1) Cell membrane: – Like any cell surrounded by semipermeable cell membrane (Flexible plastic). 2) Contents: – a) Hb is its main content (about 34% of RBC volume). – b) K+ is the main intracellular cation – c) CAE that helps CO2 carriage. – d) No mitochondria: energy derived from anaerobic glycolysis.  Functions of RBCs 1) Contain Hb, carry O2. 2) Contain CAE, Help CO2 carriage in the blood. 3) Give the blood its viscosity that determine PR and maintain BP.  Hemoglobin Hb content: 1) Adult male 14 – 16 gm/ dl 2) Adult female 13 – 15 gm/ dl 3) Child at 5 year 12 gm/ dl 4) New born 18 gm/ dl  Haematocrit value Ht = ratio of RBCs volume to total blood volume Normal values: Adult male 45% Adult female 42% Child 36% New born 55% Uses 1) Calculation of blood volume 2) Calculation of blood indices & diagnosis of anaemia Erythropoiesis  Erythropoiesis Def: formation of new RBCs Sites of erythropoiesis – Active (red) BM:  In infancy & childhood red BM present nearly in all bones  In adult red BM is restricted in ends of long bones, vertebrae, ribs, sternum, skull, pelvic bones Stages of Eythropoiesis Factors affecting erythropoiesis  Factors affecting erythropoiesis 1. O2 supply to the tissue = role of erythropoietin 2. Nutritional factors: A. Dietary protein content B. Mineral ions Iorn Copper Cobalt C. Vitamins: vit B12, folic acid, and others 3. Hormonal factors 4. State of bone marrow 5. State of liver & kidney.  1) Tissue oxygenation & erythropoietin Decrease O2 supply to the tissue (Hypoxia) is the main stimulus for erythropoiesis as in: 1. Anaemias & High altitudes 2. Lung diseases (chronic BA) & Cyanotic heart diseases) 3. Increase O2 demand as in athelets Hypoxia stimulate erythropoietin secretion which stimulate eythropoiesis in BM.  Erythropoietin A glycoprotein hormone (mw 34000 d) Source: – In normal persons: – 90% from the kidney and – 10% form the liver – In fetus: completely from the liver. Function: 1) Stimulates the differentiation of stem cells in BM into RBCs lineage. 2) Speeds up all stages of development of erythroblasts into mature RBCs  Erythropoietin Mechanism Start Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased Increases tissue demands for O2 O2-carrying ability of blood Reduces O2 levels in blood 90% of EPO is renal Erythropoietin Kidney (and liver to a Enhanced stimulates red smaller extent) releases erythropoiesis bone marrow erythropoietin increases RBC count  2) Nutritional or Dietary factors A) proteins: – Proteins of high biological value are essential for erythropoeisis (for the formation of globin part of Hb. – Prolonged protein under nutrition lead to anaemia B) Minerals: 1. Iron (Fe+) is essential for formation of haeme part of Hb. 2. Copper (Cu): Cu essential for erythropoeisis, – Co-factors in Hb synthesis – transported in the plasma by ceruloplasmin (which catalyze the oxidation of ferrous iron to ferric) 3. Cobalt (Co) – Stimulate erythropoeitin secretion from the kidney – enters in synthesis of Vit. B12 C) Vitamins: Vit B12, folic acid, others vit C Vitamin B12 & Folic acid; essential for DNA synthesis & maturation of bone marrow cells III- Dietary vitamins All vit are needed for erythropoiesis. Vit B12 & Folic acid; essential for – DNA synthesis & nuclear maturation of bone marrow cells (maturation factors). Deficiency of B12 or Folic acid leads to failure of maturation of erythroblasts leading to formation of fragile larger cells with shorter life span (Macrocytic or Megaloblastic anaemia) III- Role of Liver & kiney 1) Healthy Liver is essential for normal erythropoiesis as it the site for: 1. Storage of Vit. B12 & iron 2. synthesis of 10% of EPO  Chronic liver disease leads to anaemia 2) Healthy Kidney is essential for normal erythropoiesis: synthesis of 90% of EPO  Chronic Renal failure leads to anaemia. IV- Hormones Beside erythropoietin – Thyroid H – Androgens – Glucocorticoides All stimulate Erythropoiesis as they promote tissue metabolism V- State of bone marrow Healthy bone marrow is essential for normal erythropoiesis Destruction of BM by: - irradiation, - drugs - toxins leads to aplastic anaemia Anaemias  Anaemias Def: (caused by decrease RBCs count or Hb content or both). Hb content < 12 gm /dl for female and < 14 gm /dl for male Causes & types: 1. Blood loss anaemia – Acute blood loss (haemrrhage) lead to haemorrhagic anaemia (normocytic normochromic) – Chronic blood loss leads to iron deficiency anaemia (microcytic hypochromic) 2. Megaloblastic anaemia: vit B 12 or folic acid deficiency. 3. Haemolytic anaemia 4. Aplastic anaemia destruction or hypofunction of BM lead to pancytopenia  Megaloblastic (Macrocytic) anaemia – Deficiency of vit B12 or folic acid or intrinsic factor Caused by: – Atrophy of gastric mucosa or gastrectomy Leads to Deficiency of intrinsic factor called (pernicious anaemia). – Decrease vit B12 absorption from terminal ileum as in (inflammatory bowel disease). Pathogenesis: – Failure maturation of RBCs and production of large immature RBCs called megaloblasts (fragile) that ruptured easily.  Haemolytic anaemia Caused by haemolysis or destruction of RBCs which have short life span Causes: Intrinsic disorders Extrinsic disorders 1) Membrane defect : 1) Immune: (spherocytosis) : Microcytic a) autoimmune diseases 2) HB disorders: sickle cell b) Incompatible Bl transfusion anaemia & thalassemias 2) Bacterial toxins 3) Enzyme defect : G-6-PD 3) Chemicals or drugs: deficiency anticonvulsant & antimalarial drugs  Polycythemia Def: Increase RBCs count above normal (6 – 8 millions/ mm3) 1. Primary polycythemia (rubra vera): – RBCs count 7 – 8 millions /mm3 – Unkown cause 2. Secondary polycythemia: – RBCs count 6 – 7 millions /mm3 – Caused by tissue hypoxia: 1) People live at high altitudes 2) Lung diseases 3) Cyanotic heart disease