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Function of blood and blood plasma
Dpt. of Normal, Pathological and Clinical PhysiologyCharles University, 3rd Faculty of Medicine
The main function of blood
1. Respiration (transport of O2 a CO´2)2. Nutrition (transport of ingested nutrients)3. Transportation of waste products4. Transport of heat (for heating and cooling)5. Acid-base balance6. Water balance7. Thermoregulation 8. Immunity9. Transport of hormones (signals), vitamins and trace elements10. Hemocoagulation (hemostasis)
Main componentsWhole blood (8% of body weight) = blood elements + blood plasma
erythrocytes 4.2 – 6.0 x1012/lleukocytes 3 – 11 x109/lthrombocytes 170 – 360 x109/l
serum x plasma
Hematokrit 36% - 49%
Composition of blood plasma
watersodium 135-150 mmol/l, potassium 3.8-5.5 mmol/l, calcium 2.0-2.75 mmol/l, magnesium 0.66-0.94 mmol/lchlorides 97-108 mmol/l, bicarbonate, phosphate, sulphate, proteins 70-80 g/l glucose 3.3-6.1 mmol/l, urea 2-7.5 mmol/lviscosity (water=1): blood 4.5, plasma 2.2osmolality: 280 mosm/l (the major cation is Na, the major anions are HCO3 and Cl
Plasma proteins
Oncotic pressure (colloidal-osmotic) (3 kPa), edema
Synthesis in liverglycoprotein (except albumin)Proteins of acute phase (CRP)70-80 g/lBlood volume
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 ratio585 AK, ellipsoidal shape (15 x 3.8 nm)albuminuriatransport: FFAcids, Ca, bilirubin, steroid hormones, Cu, penicillin, aspirin
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 kDafree Hb is filtrated in kidney and may affect tubules (transfusion)Hp-Hb complex is not filtrated: iron sparing and tubules protecting effectsDecreases during hemolytic anemia (half-times of Hp-Hb and Hp), increases during inflammation (PAF)
3. Iron coupled proteins
transferin (2-4 g/l), feritin (plasma level corresponds to the body reserve), hemosiderin
hemochromatosis
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; )
5. 1-antitrypsin
The main component of 1 fraction
Inhibits the trypsin, elastase and other proteasedeficiency (mutation) results in accumulation of the 1-AT in hepatocytes, hepatitis and cirrhosis (unknown mechanism), transplantation
6. Immunoglobulins
Produced by plasma cells (B-lymphocytes)antibodies, the defense proteins
IgG IgA IgM IgD IgE
g/l 9-15 1.5-4 0.6-1.7 0-1.4
kDa 150 160 900 180 190
Erythrocytes
The most numerous cell of the human body (2.5x1013), the speed of production (2.5 mil./s), 4 kms daily diameter: 7 m, volume: 85 fl, Hb in the ery: 30 pgretikulocytes (< 1 %, 1 day lifetime), retikulocytosisThe function of the spleenhematocrite, sedimentationtransport of O2, CO2 and Acid-Base Balanceproduced in the bone marrow – vertebra, sternum, ribs (in the liver and spleen in the fetus, during early embryonic life in the yolk sac)
Price – Jones curve
3 5 7 9 11 13 um
num
ber normal
mikrocytesmakrocytes
Regulation of the erythropoesis
stimulation– erythropoietin– somatotropin– thyroxin– rennin-angiotensin– testosterone
inhibition– glucocorticoids– estrogens
tissue oxygenation (blood volume, anemia, hemoglobin, perfusion, lungs)
The Hemoglobin Structure heme – derivate of porphyrin, Fe2+ centrally imbedded (binding place) globin – polypeptide
4 subunits = 4 Fe molecules120-180 g/l
Types of globin chains
Hb A The main adult Hb
Hb B adult, 2.5% Hb
Hb F fetal, higher affinity to O2
Gower I embryonic
Gower II embryonic
physiological: oxyhemoglobin, carbaminohemoglobin
pathological: carboxyhemoglobin, methemoglobin
Hemoglobin saturation curve
Right handed shift = decrease of the affinity = increase of the oxygen release:
1. decrease of pH (Bohr effect)
2. Increase of pCO2
3. Increase of temperature
4. Increase of 2,3-DPG (product of anaerobic glykolysis (for NaK ATPase), binds to the Hb, not to the oxyHb)
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 hemoglobinHeme – biliverdin – bilirubin (bile)
Myoglobin
In the muscle tissuesat. curve shifted to the left– Oxygen is released only
under very low levels of pO2 (long-term contraction)
– Binds oxygen from the blood hemoglobin
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/lapoferritin (mucosa), transferrin (2 Fe3+; plasma; 1-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
The iron distribution
3%
27%
70%
hemoglobinferitinmyoglobin
Hemochromatosis
AR, mutation of the 6. chromosomeAccumulation of the hemosiderin in the liver, pancreas, heart, kidney, adrenal glands, testes and hypofysisarthropaty, skin pigmentation, DMFailure of the liver, cirrhosisDg: liver biopsy, plasma ferritin, saturation of the transferin
Anemia
Decrease of the hemoglobin and number of erythrocytesDisorder 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: -thalasemie, -thalasemie, sickle-cell anemiaLack of Fe: hemorrhages (GIT)Hemolytic anemia: glu-6-PDH, snake poisoning
Sickle-cell anemia
Mutation in the -chain (G6V)HbS hemoglobinSickle, lunar shape of erythrocytes, loose their elasticity and obstruct the vessels (spleen, kidney)central AfricaProtect against malaria – advantage in selection
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
Polycytemia
primary x secundary7-8 mil. ery, HK 70%polycythaemia vera: rare, blue-red color of the skin, scleral hyperemia, neoplastic
Leukocytes
leukocytes 3 – 11 x109/l = 3000 – 11000/lheterogennic population, only one common parameter – the defense function: defense against tumors, bacterial, viral and parasitical infections
Types of white blood cells
poly-morpho-nucleargranulocytes
neutrophils 3000-6000/l 50-70%eosinophils 150-300/l 1-4%basophils 0-100/ l 0-0.5%
lymphocytes 1500-4000/l 20-40%monocytes 300-600/l 2-8%
the functionneutrophils: second line of defense; shield against invading bacteria, chemotaxis (diapedesis, amoeboid motion), phagocytosiseosinophils: 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 defenselymphocytes:– T-lymphocytes: cell immunity (helper, suppressor, cytotoxic, memory cells)– B-lymphocytes: humoral immune defense (plasma cells, memory cells)