Function of blood and blood plasma

1. Function of blood and blood plasma Dpt. of Normal, Pathological and Clinical Physiology Charles University, 3rd Faculty of Medicine

2. The main function of blood • Respiration (transport of O2 a CO´2) • Nutrition (transport of ingested nutrients) • Transportation of waste products • Transport of heat (for heating and cooling) • Acid-base balance • Water balance • Thermoregulation • Immunity • Transport of hormones (signals), vitamins and trace elements • Hemocoagulation (hemostasis)

3. Main components • Whole blood (8% of body weight) =blood elements + blood plasma • erythrocytes 4.2 – 6.0 x1012/l • leukocytes 3 – 11 x109/l • thrombocytes 170 – 360 x109/l • serum x plasma • Hematokrit 36% - 49%

4. Composition of blood plasma • water • sodium 135-150 mmol/l, potassium 3.8-5.5 mmol/l, calcium 2.0-2.75 mmol/l, magnesium 0.66-0.94 mmol/l • chlorides 97-108 mmol/l, bicarbonate, phosphate, sulphate, proteins 70-80 g/l • glucose 3.3-6.1 mmol/l, urea 2-7.5 mmol/l • viscosity (water=1): blood 4.5, plasma 2.2 • osmolality: 280 mosm/l (the major cation is Na, the major anions are HCO3 and Cl

5. Plasma proteins • Oncotic pressure (colloidal-osmotic) (3 kPa), edema • Synthesis in liver • glycoprotein (except albumin) • Proteins of acute phase (CRP) • 70-80 g/l • Blood volume

6. 1. Albumin • 32-45 g/l, 69 kDa, 60 % of all plasma proteins, 80 % of oncotic pressure • 12 g/day produced in liver (25 % of capacity) • Liver diseases – decrease of A:G ratio • 585 AK, ellipsoidal shape (15 x 3.8 nm) • albuminuria • transport: FFAcids, Ca, bilirubin, steroid hormones, Cu, penicillin, aspirin

7. 2. Haptoglobin • Glycoprotein binding free Hb (10 % Hb of destroyed erythrocytes, the rest breaks down into globin, hem and iron), 0.4- 1.8 g/l of Hp, the same amount of Hb, 90 kDa • free Hb is filtrated in kidney and may affect tubules (transfusion) • Hp-Hb complex is not filtrated: iron sparing and tubules protecting effects • Decreases during hemolytic anemia (half-times of Hp-Hb and Hp), increases during inflammation (PAF)

8. 3. Iron coupled proteins • transferin (2-4 g/l), feritin (plasma level corresponds to the body reserve), hemosiderin • hemochromatosis

9. 4. Ceruloplazmin • 2-globulin, 160 kDa, 0.3 g/l • Transfer of 90 % of copper (6 atoms bind to one molecule), the rest is transported bound to albumin, easy release = probably more important) • Connected to the Wilson disease (hepatolenticular degeneration, AR, storage of copper in the brain, cornea, kidney and liver, high intestinal adsorption and low liver excretion of copper; Hepatitis, anemia, neurological signs, Kayser-Fleischer ring; )

10. 5. 1-antitrypsin • The main component of 1 fraction • Inhibits the trypsin, elastase and other protease • deficiency (mutation) results in accumulation of the 1-AT in hepatocytes, hepatitis and cirrhosis (unknown mechanism), transplantation

11. 6. Immunoglobulins • Produced by plasma cells (B-lymphocytes) • antibodies, the defense proteins

12. The most numerous cell of the human body (2.5x1013), the speed of production (2.5 mil./s), 4 kms daily diameter: 7 mm, volume: 85 fl, Hb in the ery: 30 pg retikulocytes (< 1 %, 1 day lifetime), retikulocytosis The function of the spleen hematocrite, sedimentation transport of O2, CO2 and Acid-Base Balance produced in the bone marrow – vertebra, sternum, ribs (in the liver and spleen in the fetus, during early embryonic life in the yolk sac) Erythrocytes

13. Price – Jones curve

14. Regulation of the erythropoesis • stimulation • erythropoietin • somatotropin • thyroxin • rennin-angiotensin • testosterone tissue oxygenation (blood volume, anemia, hemoglobin, perfusion, lungs) • inhibition • glucocorticoids • estrogens

15. The Hemoglobin Structure • heme – derivate of porphyrin, Fe2+ centrally imbedded (binding place) • globin – polypeptide 4 subunits = 4 Fe molecules 120-180 g/l

16. Types of globin chains physiological: oxyhemoglobin, carbaminohemoglobin pathological: carboxyhemoglobin, methemoglobin

17. Hemoglobin saturation curve • Right handed shift = decrease of the affinity = increase of the oxygen release: • decrease of pH (Bohr effect) • Increase of pCO2 • Increase of temperature • Increase of 2,3-DPG (product of anaerobic glykolysis (for NaK ATPase), binds to the Hb, not to the oxyHb)

18. Fetal hemoglobin • 37 AA out of 146 differ from the chain (adult one) • Binds low 2,3-DPG, shifted to the left compared with the adult one at the same level of pO2 • Hemoglobin saturation curve shifted to the left DEGRADATION of the hemoglobin Heme – biliverdin – bilirubin (bile)

19. Myoglobin • In the muscle tissue • sat. curve shifted to the left • Oxygen is released only under very low levels of pO2 (long-term contraction) • Binds oxygen from the blood hemoglobin

20. Metabolism of the Iron • food: Fe3+x more absorbable Fe2+ • Gastric juice (acidity, gastroferrin) and vitamin C reduces Fe, (following partial gastric resection sideropenic anemia develops • Absorbed in the upper part of small intestine (duodenum) • Fe2+plasma level 10-35 mol/l • apoferritin (mucosa), transferrin (2 Fe3+; plasma; b1-globulin), ferritin (4500 Fe3+; spleen, liver, bone marrow; plasma ferritin, rapidly available iron reserve), hemosiderin (aggregated ferittin, is less readily mobilized) • Iron requirement: 0.2 mmol/day (adsorption 6% in male, 12 % in female = 0.02 mmol/d losses per day; high req. (0.5 mmol/day) during menstruation, second half of pregnancy and after delivery

21. The iron distribution

22. Hemochromatosis • AR, mutation of the 6. chromosome • Accumulation of the hemosiderin in the liver, pancreas, heart, kidney, adrenal glands, testes and hypofysis • arthropaty, skin pigmentation, DM • Failure of the liver, cirrhosis • Dg: liver biopsy,  plasma ferritin,  saturation of the transferin

23. Anemia • Decrease of the hemoglobin and number of erythrocytes • Disorder of the erythropoiesis: aplastic a., renal a. (erythropoietin) • Disorders of the DNA synthesis: megaloblastic a. (lack of folic acid or vitamin B12) • Disorders of the Hb synthesis: b-thalasemie, a-thalasemie, sickle-cell anemia • Lack of Fe: hemorrhages (GIT) • Hemolytic anemia: glu-6-PDH, snake poisoning

24. Sickle-cell anemia • Mutation in the b-chain (G6V) • HbS hemoglobin • Sickle, lunar shape of erythrocytes, loose their elasticity and obstruct the vessels (spleen, kidney) • central Africa • Protect against malaria – advantage in selection

25. Megaloblastic anemia • Folic acid (folate) • Low intake or poor adsorption (maladsortion) • Storages available for several month • antagonists: fluorouracyl, methotraxat (employed in tumor therapy as cytostatic agents) => aplastic anemia • cyanocobalamines (vitamin B12) • Participates in the folat metabolism • Low intake in vegetarians • Storage available for years • Need of intrinsic factor

26. Polycytemia • primary x secundary • 7-8 mil. ery, HK 70% • polycythaemia vera: rare, blue-red color of the skin, scleral hyperemia, neoplastic

27. Leukocytes • leukocytes 3 – 11 x109/l = 3000 – 11000/l • heterogennic population, only one common parameter – the defense function: defense against tumors, bacterial, viral and parasitical infections

28. Types of white blood cells

29. the function • neutrophils: second line of defense; shield against invading bacteria, chemotaxis (diapedesis, amoeboid motion), phagocytosis • eosinophils: mucous immunity, against non-phagocytable agents (mostly parasites) • basophiles: immediate allergic reaction (anaphylactic shock), release of histamin, heparin… • monocytes: 72 h circulating, then migration into tissues (RES), phagocytosis, first line of defense • lymphocytes: • T-lymphocytes: cell immunity (helper, suppressor, cytotoxic, memory cells) • B-lymphocytes: humoral immune defense (plasma cells, memory cells)