THE BLOOD

Topics
Body fluids
Intracellular fluid, extracellular fluid.

Blood constituents & their functions

Plasma
Plasma proteins & colloidal osmotic pressure Electrolytes & crystal osmotic pressure Water

Homeostasis

Cellular elements : Erythrocytes, Leukocytes

Hemostasis Blood groups

& Platelets

Body fluids
Total body water (by weight) is about 60%. 40% is ICF & remaining 20% is ECF (3/4th ISF & 1/4th plasma)

Functions of blood
Transportation
O2 & CO2 Nutrients Waste products Hormones etc.

Regulation
pH Body temperature

Protection
Immunity Blood coagulation

Components of blood
Plasma Blood cells (Formed elements)
Erythrocytes or Red blood cells (RBC) Leucocytes or White blood cells (WBC) Thrombocytes or Platelets

Hematocrit

Plasma
Composition: Water (92%) Proteins (6~8%) Inorganic constituents (~1%) Na+, Cl-,
K+,Ca2+, etc.

Nutrients Waste products (nitrogenous waste like urea) Dissolved gasses (O2 & CO2) Hormones

Plasma proteins
Albumins (60-80%)
Most important in maintenance of osmotic balance Produced in liver

Globulins (1, 2, 1, 2 & )

Important in transport of materials through the blood (eg: Iron (transferrin), thyroid hormone (transthyretin) etc) Clotting factors Produced by liver, except -globulins which are immunoglobulins synthesized by lymphocytes

Fibrinogen
Important in clotting Produced by liver

Plasma osmotic pressure

Crystalloid osmotic pressure
Pressure generated by all crystal substances, particularly electrolytes Important in maintaining fluid balance across cell membrane

Colloid osmotic pressure

Osmotic pressure generated by plasma proteins, especially albumin. Important in fluid transfer across capillaries

Erythrocytes
Morphology
Biconcave discs Without a nucleus

RBC count

: 4.5~5.5million cells
per cubic mm of blood or 4.5~5.5 x 1012/L

: 3.8~4.6million cells
per cubic mm of blood or 3.8~4.6 x 1012/L

Functions of hemoglobin
Carries oxygen from lungs to tissue, and carbon dioxide from tissues to lungs. It is an excellent acid-base buffer Normal values: - 12~16 g/dL, - 11~15 g/dL

Erythrocyte sedimentation rate

The distance that RBCs settle in a tube of blood in one hour. Normal value:

- 0~15mm, - 0~20mm
Rouleaux formation

ESR is an indication of inflammation which increases in many diseases, such as tuberculosis, rheumatoid arthritis etc.

Osmotic fragility

The susceptibility of a red blood cell to break apart when exposed to saline solutions of a lower osmotic pressure than that of the human cellular fluid Osmotic fragility is more in spherocytosis, megaloblastic & microcytic anemia etc.

Carbonic anhydrase of RBC

Enzyme that catalyzes the reversible reaction between CO2 and H2O to form H2CO3 (carbonic acid) is CA. This reaction makes it possible for the water of the blood to transport enormous quantity of CO2 in the form of bicarbonate ion (HCO3-). In tissue capillaries CO2 combines with water inside the RBC to form carbonic acid that dissociates to form bicarbonate ions & hydrogen ions. The chloride shift is the movement of chloride ions into RBC as bicarbonate ions move out.

Hemopoesis

In embryonic life first RBCs are produced by yolk sac, which is later on taken up by mainly liver, & also by spleen & lymph nodes.
During last month of gestation & after birth the RBC is synthesized exclusively from bone marrow.

Erythropoesis
Proerythroblasts are formed from CFU-E cells after stimulation

First generation cells are basophil erythroblast with little Hb.

In succeeding generations the Hb conc. steadily increases. The nucleus condenses & get extruded from cell, & ER also reabsorbed at the stage of reticulocytes. Reticulocytes move to capillaries by a process called diapedesis. Within 1 or 2 days it is turned into a mature RBC.

Factors effecting erythropoiesis

Tissue oxygenation is the most essential regulator of RBC production. Hypoxia cause erythropoietin formation from kidneys (90%) & liver. Erythropoietin stimulate production of proerythroblast from stem cells & also speeds up the rest of process, but new RBCs are found in circulation after 5 days.

Nutrient requirement for erythropoiesis

Many vitamins, minerals & proteins are required for RBC production. Clinically, Folic acid, Vit. B12, and iron are the most important. Deficiencies in these result in characteristic anemia. Megaloblastic anemia & pernicious anemia

Destruction of RBC
Average lifespan of RBC is about 120 days RBC lack nucleus, mitochondria, ER etc., but have enzyme system which regulate
Glucose metabolism for production of ATP Maintain pliability (flexibility) of plasma membrane Iron of Hb is kept in ferrous form rather than ferric Prevent oxidation of proteins in RBC

Red cells self destruct, as the membrane becomes fragile, when they pass through 3m wide red pulp of spleen. Kupffer cells & other macrophages phagocyte the Hb & release iron to blood, transported by transferrin to be reused in Hb synthesis. The porphyrin is converted into bilirubin (bile pigment).

White Blood Cells

Types of WBC

Granulocytes Agranulocytes

WBC count
Granulocytes or polymorphonuclear leukocytes are of three types neutrophils with neutrophilic granules & multilobed nucleus, eosinophils with acidic granules & spectacle shaped bilobed nucleus, and basophils with coarse basophilic granules & bilobed nucleus. These granules contain active substances involved in inflammatory & allergic reactions.

WBC

% of total white cell

Neutrophils
Eosinophils Basophils Lymphocytes Monocytes

50-70
1-4 0-1 20-40 2-8

Agranulocytes are lymphocytes & monocytes. Lymphocytes have large round nucleus with scanty cytoplasm, and monocytes have abundant agranular cytoplasm and kidney-shaped nuclei.

 Neutrophils: Remain in circulation for about 10-12 hrs & then move into other tissues where they become motile and leak out, & phagocytize bacteria, antigen-antibody complexes etc. They contain lysozymes which can destroy certain bacteria.
Eosinophils: Leave circulation & enter tissues having inflammatory reactions. It produces anti-inflammatory chemicals that destroys chemicals like histamine. They attacks certain worm parasite. Their numbers are elevated in blood of people with allergy & parasitic infection.

Basophils: Play a role in allergic & inflammatory reactions. Release histamine, which cause inflammatory reactions, & heparin, which inhibits blood clotting.

 Lymphocytes:

Smallest WBC. Although lymphocytes originate in bone marrow, they migrate to lymphatic tissues (lymph nodes & nodules, spleen, tonsils, thymus) where they can proliferate & produce more lymphocytes.

B cells mainly produce antibodies & other chemicals responsible for destroying microorganism. T cells act against viruses, & are responsible for graft rejection, tumor control etc. Lymphocytes also contributes to allergic reactions & regulation of immune system.

Monocytes: Largest WBC. Leave circulation & get

transformed into macrophages & phagocytize bacteria, cell debris etc. Increase in monocyte is associated with chronic infections. It also act as antigen presenting cell, which can activate lymphocytes.

Platelets

Formed in bone marrow from cells called megakaryocytes. Doesnt have nucleus, but can secrete variety of substances. 2-4m in diameter, Lifespan: 7~14 days. Play an important role in hemostasis.

Hemostasis
The arrest of bleeding following injury and it is the result of three interacting, overlapping mechanisms.
Vascular spasm
Formation of platelet plug Blood coagulation (clotting)

Vascular spasm
Local myogenic spasm (initiated by direct damage to vascular wall)

Local autacoid (physiologically active internal secretion) factors from the traumatized tissues (endothelin & tissue factor) & platelets (serotonin & thromboxane A2 prostaglandin derivative)
Nervous reflexes (initiated by pain receptors)

Aspirin (anti-inflammatory, antipyretic pain killer) act by inhibiting prostaglandin synthesis. It inhibits production of thromboxane & hence reduce platelet activation.

Platelet contents
Actin, myosin, & another contractile protein thrombosthenin, causing platelet contraction. Residuals of ER & Golgi apparatus synthesize various enzymes & stores calcium.

Mitochondria produce ATP & ADP. Enzyme system synthesizing various prostaglandin.
Contain fibrin stabilizing factor (factor XIII), which helps in final step of coagulation. Platelet derived growth factor cause endothelial cells, vascular smooth muscles, & fibroblasts to multiply & grow.

Platelet activation

Mechanism of platelet plug formation

Platelets when come in contact with damaged vascular surface, especially collagen, they get activated. Begin to swell, form irradiating pseudopods, contractile proteins cause the release of granule contents (ADP & thromboxane A2), which makes the platelets sticky, & they stick on to collagen and to another protein called von Willebrand factor (vWF), a plasma protein which leaks into traumatized tissue. Activated platelets attracts other platelets & activate them, & they stick to each other, forming the platelet plug. The platelet plugging mechanism is important in closure of minute ruptures in small blood vessels. Its deficiency (thrombocytopenia) may result in purpura.

Blood coagulation
Clotting factors I II III IV V VII VIII IX X XI XII XIII Synonyms Fibrinogen Prothrombin Thromboplastin, Tissue factor Calcium Proaccelerin, labile factor Proconvertin, stable factor Antihemophilic factor A (AHF-A) Christmas factor, AHF-B Stuart-Prower factor Plasma thromboplastin antecedent, AHF-C Hageman factor, glass factor Fibrin stabilizing factor, Laki-Lorand factor

3 steps & 2 pathways

Fibrin stabilization

Scanning electron micrograph of clot

Final clot with entangled blood cells

Blood groups
Erythrocytes on their surfaces carry many antigens, but the most important & commonly recognized are the A & B substances and Rhesus (Rh) factor

Rh group
Inherited independent of ABO system

Rh +ve : Antigen present (mainly D antigen) & no antibody Rh ve : No antigen & antibodies will be produced if exposure occurs