Physiology Unit 3 HEMATOLOGY

In Physiology Today

Hematocrit Percentage of blood volume that is erythrocytes 45% in men 42% in women Average blood volume in is 5 L

Plasma Large amounts of organic/inorganic substances dissolved in water Serum Plasma with fibrinogen and other clotting factors removed Plasma proteins are made by the liver Albumins Most abundant Globulins Different categories Some made by immune cells Fibrinogen Clotting

Human Blood Formed Elements

Erythrocytes Contain hemoglobin (Hb) Transport O 2, some CO 2 O 2 binds to Fe 3+ in Hb molecules Average [Hb] Women 14 g/100 ml Men 16g/100 ml 7 μm in diameter High SA/V Life span 120 days Erythropoiesis Erythrocytes produced by red marrow Iron, Vitamin B 12, folic acid necessary

Iron Iron lost per day needs to be replaced by dietary intake Total iron 50% total iron in Hb 25% in cytochromes 25% in liver ferritin Iron recycling is very efficient Transferrin Iron transport protein Delivers iron to bone marrow

Vitamin B 12 and Folic Acid Vitamin B12 Required in small amounts (1 millionth of a gram/day) Required for the action of folic acid Found only in animal products Intrinsic factor is necessary for vitamin B 12 absorption A protein secreted by the stomach Folic Acid Found in leafy plants, liver, yeast Essential for DNA formation Required for thymine synthesis Causes impairment of cell division when not present in adequate amounts Fewer erythrocytes produced

Regulation of Erythrocyte Production Erythropoietin Secreted by kidney, liver Acts on bone marrow to stimulate production of erythrocytes Increased secretion when less O 2 delivered to kidneys Testosterone also stimulates release of erythropoietin

Leukocytes Produced by bone marrow Monocytes and many lymphocytes undergo further development outside the bone marrow

Platelets Fragments of large cells called megakaryocytes Involved in blood clotting Clot formation can not occur without platelets

Stem Cells Totipotent stem cells Can give rise to any extra-embryonic (chorion, amnion, placenta) AND embryonic (adult) cells Pluripotent stem cells Can give rise to any embryonic (adult) cell Multipotent stem cells Can only give rise to certain cell lines (i.e. bone marrow stem cells) Adult stem cells Umbilical cord stem cells

Blood Cell Production

Hemostasis Prevention of blood loss (stoppage of bleeding) Injuries to small vessels (arterioles, capillaries, venules) Immediate response to injury is vasoconstriction Reduces flow to the area Presses together the sides of the endothelium Induces stickiness glues the endothelium together Requires 2 processes 1. Platelet plug formation 2. Blood coagulation (clotting)

Formation of a Platelet Plug 1. Platelet adhesion Exposed collagen in connective tissue von Willebrand factor Secreted by endothelial cells and platelets 2. Triggers platelet activation Release contents of secretory vesicles that act locally 3. Triggers platelet aggregation Formation of platelet plug

Platelet Plug Localization Adjacent, undamaged endothelial cells release prostacyclin (PGI 2 ) Strong inhibitor of platelet aggregation Adjacent, undamaged endothelial cells also release NO Vasodilator Inhibits platelet adhesion, activation and aggregation

Blood Coagulation Clot Formation The transformation of blood into a solid gel called a clot or thrombus Consists mainly of fibrin Clotting occurs locally around the platelet plug Function is to support and reinforce the platelet plug and to solidify blood that remains in the wound channel

Clotting Pathway Role of Thrombin Cascade of events leads to the conversion of prothrombin (plasma protein) to thrombin Thrombin catalyzes the split of fibrinogen to loose fibrin Fibrin network then becomes stabilized Thrombin also stimulates platelet activation

Clotting Pathway

Clotting Pathway Role of Platelets Clotting can not occur in the absence of platelets Activated platelets are essential because several of the cascade reactions take place on the surface of activated platelets Activated platelets display specific membrane receptors that bind several of the clotting factors which permits the reactions to occur

Clotting Pathway Thrombin Burst Intrinsic pathway Everything necessary for this pathway is in the blood Extrinsic pathway A cellular element outside the blood is needed Tissue factor Not a plasma protein Located on the outer plasma membrane of fibroblasts

Dissolving the Clot Fibrinolytic System A fibrin clot is a temporary fix until the blood vessel is repaired Plasminogen is activated to plasmin Plasmin digests fibrin which dissolves the clot

Sickle Cell Anemia