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)