BLOOD

Blood is the combination of Formed Elements (red blood cells, white blood cells, thrombocytes or platelets) and Plasma.

The Components of Blood

Plasma: Makes up about 55% of blood.

Fluid -- water (90%), electrolytes, proteins, hormones, metabolites, gases.

Plasma Proteins:

• Albumins: 60%. Key function is to help water retention (osmotic balance); albumin also binds some hormones (thyroxin), fatty acids, pigments and drugs (e.g., penicillin & barbituates).
• Globulins: 40% Carry fats (HDL & LDL), hormones, clotting factors, and fat-soluble vitamins. Antibodies are "gamma globulins." Transferrin -- iron and copper binding protein (actually, a beta-globulin)
• Fibrinogen -- precursor of fibrin which forms blood clots (actually, a beta-globulin)

Serum is the fluid left after clotting. Plasma has fibrin and fibrinogen, serum doesn't.

Formed Elements

Red Blood Cells, White Blood Cells and Platelets.

45% of blood on average.

Hematocrit is measure (percent) of red blood cells

• Gender differences and changes with state of health and altitude.

Red Blood Cells

Erythrocytes -- have no nuclei or mitochondria (relies on glycolysis for energy). RBCs are essentially bags of hemoglobin, the oxygen binding protein. They also contain carbonic anhydrase, an enzyme that converts carbon dioxide to bicarbonate, an important factor in acid-base balance of body. Flexible cells - can fit into narrow capillaries. Made in bone marrow. Short life span (3-4 months) because of lack of nucleus. Removed by spleen when they are worn out.

Erythropoietin: hormone produced by kidney which stimulates bone marrow to produce RBCs.

• Epogen or "EPO" is human erythropoietin produced via biotechnology and is used to treat anemia in kidney dialysis and cancer patients. EPO has also been used to boost RBC content of athletes:
  Immature RBCs :

When blood is produced too quickly (e.g., when one is overcoming anemia), immature RBCs are often present in circulatng blood. The nucleus may not be completely removed or degraded.

Spherocytosis: Abnormally shaped RBCs due to lack of spectrin, a cytoskeletal protein which lines the inside of the RBC membrane.

Hemoglobin
Heme: iron containing pigment. Binding site for oxygen. Site can also bind carbon monoxide strongly -- basis of carbon monoxide poisoning. Carbon dioxide binds to globins (forming carbaminohemoglobin).

Globin: protein. 4 Subunits: 2 alpha and 2 beta subunits.

Hemoglobin has bluish color when it doesn't have bound oxygen, and reddish color with it has oxygen attached.

Hemoglobin loads up with oxygen in lungs and delivers oxygen to cells.When RBCs are destroyed, hemoglobin is degraded. Iron is recycled and globin is degraded. Heme is converted into bilirubin which is transported to liver where it is secreted in bile. If liver is damaged (cirrhosis in alcoholism or damage from hepatitis), bilirubin builds up in blood and imparts a yellow color to skin and eyes called jaundice. In infants with excess bilirubin, light is used to convert bilirubin into a soluble byproduct which can be excreted in urine.

Anemia: abnormally low amount RBC or hemoglobin. Variety of factors.

• Hemorrhagic: due to blood loss.
• Iron deficiency: decreases hemoglobin levels producing "hypochromic microcytic anemia" which means.....
• Aplastic: from low production of RBCs due usually to toxins (chemicals, viruses, & radiation)
• Hemolytic: damage to RBCs from parasites, antibodies, or weak cells (Thalassemia).
• Pernicious: Vitamin B12 deficiency typically caused by intrinsic factor deficiency. B12 is necessary for RBC development.
• Sickle cell: genetic "defect" in hemoglobin structure (one amino acid difference in beta subunit). Cells will form sickle shape when cells are in lower oxygen environment.
  Why is it common in people of African descent? -- Sickle cell and Malaria. Shorter explanation.
  Treatments: bone marrow transplantation. Hydroxyurea increases fetal hemoglobin.

Beta Thalassemia minor: microcytic and hypochromic. RBCs (small cells with low hemoglobin levels). Abnormally shaped cells also present.

Polycythemia: "too many" blood cells (high hematocrit). From overproduction (Polycythemia vera, genetic) or from fluid loss, altitude acclimitization or blood doping (called secondary polycythemia, relative polycythemia, stress polycythemia or erythrocythemia if only RBCs are in excess).

Blood Types--ABO system

A or B or A+B antigens (agglutinogens) present on RBC surface.

Type O--neither A or B antigens on RBCs. If a person is Type A, he/she will have anti-B antibodies (agglutinins) in their plasma. These "built in" antibodies are due to immunity to intestinal bacteria which have similar antigens.

Basis of transfusion reactions.

• Type O--universal donor.
• Type AB -- universal recipient.

Rh factor (named for its presence on rhesus monkey blood cells) 85% of people (Europeans?) have the Rh factor (Rh-positive, Rh+). Lack of Rh factor is termed Rh-negative (Rh-). If mother is Rh- and fetus is Rh+, mother's immune system may attack fetus (happens usually after second pregnancy with an Rh+ baby -- prior exposure to Rh+ antigen is necessary). Hemolytic disease of the newborn.

Pop Quiz: A patient with internal bleeding is rushed into the E.R.. The E.R. doctor calls out for 2 units of 0-negative blood. Why O-negative?

Leukocytes (WBCs)

Granular (polymorphonuclear leukocytes): irregular nuclei & granules in the cytoplasm.

3 Classes based on staining characteristics of cytoplasmic granules.

1. Neutrophils
2. Eosinophils
3. Basophils

Agranular WBCs: 2 Classes

1. Lymphocytes
   • B-cells: antibody producing cells
   • T-cells: assist, mediate B-cell responses
2. Monocytes: phagocytes.
   • Mononucleosis ("mono" for short). Increased number and changes are seen in monocytes when fighting off certain viruses.

Neutrophils and Monocytes are phagocytic: they engulf bacteria and "foreign" material.

Neutrophils can migrate out of capillaries (process called diapedesis) and attack foreign invaderss in the surrounding tissue.

Margination: when neutophils (aka polymorphonucleocytes or PMNs) line up along vessel walls.

Leukemia: cancer due to uncontrolled leukocyte production. Cells are abnormal and crowd out other cells in bone marrow causing anemia and clotting problems.

Thrombocytes or Platelets: Fragments of MegakaryocytesRole in clotting of blood (hemostasis)

Hemostasis/Blood Clotting

Damage to vessel results in 3 phases of hemostasis:

1. Vasoconstriction due to contraction of smooth muscle.
2. Platelet phase - damage to endothelium results in platelets sticking to collagen of vessel--> platelets release secretory granules--> ADP, serotonin and thromboxane A2 (PG)--> further vasoconstriction & platelets become sticky (platelet activation)--> leads to platelet aggregation--> forms platelet plug.
3. Coagulation phase - chemicals released by platelets and damaged tissue set in motion a series of events (a cascade) that lead to blood coagulation (fibrin formation and clot formation).

• Platelet plug is reinforced by fibrin polymers
• Fibrin is a product of fibrinogen.
• Thrombin changes fibrinogen to fibrin
• Factor X changes converts prothrombin to thrombin.
• What activates Factor X?--intrinsic or extrinsic pathways.

• Intrinsic--clotting factors activated by exposure to a variety of agents (collagen, glass). Cascade of clotting factors XII --> XI --> IX etc. Called intrinsic because:......
• Extrinsic--Thromboplastin from damaged tissue activates clotting factors. Called extrinsic because:........ Which pathway is quicker? Why?
• Dissolution of Clots
  Clotting factor XII activates factors (enzymes) which breakdown fibrin clots. Fibrinolysis is activated by plasmin. One factor, bradykinin, causes vasodilation.
• Hemophilia: Hereditary diseases due to lack of a clotting factor. Sex-linked disease. Males are primarily affected. Types of Hemophilia: A & B.

Anticoagulants

• Heparin: inhibits thrombin's action (via anti-thrombin III) when there is no bleeding. Secreted by:
• Hirudin: from leeches. inhibits thrombin directly.
• Aspirin: inhibits platelet from sticking together. A prostaglandin synthesis inhibitor.
• Urokinase and streptokinase digest fibrin.
• Citrate and oxylate bind calcium which is need to convert prothrombin to thrombin.
• TPA (tissue plasminogen activator)
• Warfarin: antagonist to vitamin K.