BLOOD

PHYSIOLOGY By Dr. Olivar Functions of the BLOOD Homeostasis (regulates internal environment) Respiratory (transport of oxygen) Nutritive (carrier of nutrients) Excretory (carrier of waste products) Endocrinology (transporter of secretions) Helps maintain acid-base balance Maintenance of water and electrolyte balance and regulation of total osmotic pressure Immunity to diseases (WBC) Regulation of body temperature Normal Blood Volume Commonly: Males would have 5 liters Females would have 4.5 liters *Regardless of this, blood should be 60% Plasma, 40% Formed elements. *When centrifuged: --upper portion is plasma --white substance a.k.a. buffy coat contains WBC and Platelets --Red portion is the red blood cells Composition of Blood Plasma water - 91 92% Plasma protein albumin, globulin, fibrinogen, prothrombin Functions of Plasma Proteins Maintenance of water balance between the intravascular compartment and extra vascular spaces (proteins serve as solutes that attract plasma inside the blood vessel) Ex. Decreased Plasma Protein con.higher plasma con.plasma exits into the interstitial space HIGHER TO ------ LOWER CONCENTRATION Clinical Correlation: Patients with liver diseases manifest with Edema because the liver is where proteins are synthesized. With a liver problem, plasma protein may be depleted. In such situation, the plasma will be pushed toward the interstitial space. Imparts viscosity to the blood Source of antibodies Necessary for coagulation Maintains acid-base balance Determines specific gravity of plasma Formation of enzymes; transport of hormones and enzymes

Other contents--- 1. Water 2. Plasma proteins 3. Blood sugar glucose 4. Lipids cholesterol, phospholipids, neutral fats 5. Salts Na, K, Cl, bicarbonates, phosphates 6. Gases O2, CO2, Nitrogen 7. Special plasma substances hormones, enzymes, antibodies RBC, WBC, PLATELETS- all come from a single cell in the bone marrow called the pluripotent hematopoietic stem cells RED BLOOD CELLS Not spherical; biconcave discs; 2.5 um thick, 7.5 8 um in diameter Very deformable Carries hemoglobin in the circulation 1gm of Hgb 1.34 ml of O2 Non-nucleated in the circulating blood Anemia- any value lower than normal limit of Hgb and RBC Polycytemia- any value higher than normal limit of Hgb and RBC RBC count: Hemoglobin: Men: 5-6 x 10 (12)/L Men: 14 17 g/dL Women: 4-5 x 10(12)/L Women: 12 15 g/dL Infants: 6-5 x 10(12)/L Hematocrit: Men: 0.40 0.50 Women: 0.38 0.48 RED CELL Production Stage of Life 8 weeks of embryonic life or first 2 months Middle trimester of pregnancy rd 3 trimester of pregnancy 20 years and above

Organ Responsible for RED CELL production Yolk sac Liver, spleen, lymph nodes The bone marrow then takes over Bone marrow of skull, vertebrae, ribs, sternum

Erythropoiesis- is the process of red cell production

Proerythroblast

Early Erythroblast

Late Erythroblast

Normoblast

What happens during intermediate phase? Hemoglobin is incorporated into the cell. The nucleus condenses so that it is released from the cell even before the cell is extruded from the bone marrow. First cell released is called Reticulocyte. Reticulocyte- still colors blue because of cytoplasmic materials -after 2 days, the cytoplasmic materials are gone and mature non-nucleated erythrocytes are produced *Vit.B12 and Folic Acid are essential for RBC maturation. *Without VitB12 and Folic Acid, DNA synthesis is impaired With a problem in DNA synthesis, erythropoiesis proceeds slowly Intermediate cells are released into the circulation as Macrocytes, which are flimsy and easily rupture. Structural abnormalities Megaloblastic Anemia- is described as macrocytic and hyperchromatic Pernicious Anemia- is a condition characterized by the absence of parietal glands in the stomach which are needed for the secretion of Intrinsic Factors (IF). -Intrinsic factors (IF) aid in the absorption of Vit B12 Absence of IF malabsorption of B12 B12 deficiency Pernicious Anemia Megaloblastic Anemia Sprue- also causes megaloblastic anemia due to decreased intestinal absorption of Folic acid and Vit B12

Control of RBC Production 1. Stimulated by hypoxia. 2. Inhibited by rise in circulating RBC levels 3. Controlled by circulating hormone called erythropoietin. ExampleLiving in high altitudes where oxygen is not as abundant as in low lands---more RBC is produced. --Patients with tuberculosis have normal blood levels and oxygen levels in blood, but suffer from impaired oxygen absorption in the lungs. Thus, the body is triggered to produce more blood. Erythropoietin- is a glycoprotein hormone that controls RBC production by stimulating bone marrow -synthesized by both kidneys (90%) and the liver (10%) -increases production of PROERYTHROBLASTS Destruction of RBC Life span--- 120 days Destruction--- 1% of red cells is replaced daily Total red cell volume is replaced every 4 months Site--- Spleen * The number of red cells in the circulation is determined by the balance between production and destruction. Hypertonic solution- causes shrinkage of RBC Hypotonic solution- causes swelling of cell and eventual rupturing Isotonic solution- no change; equilibrium; 0.9% NaCl; 5% dextrose Hemoglobin Formation I. 2 succinyl Coa + 2 glycine pyrrole molecule II. 4 pyrroles protoporphyrin IX III. Protoporphyrin IX + Fe Heme IV. Heme + globin Hemoglobin chain (a or B) V. 2 a chains + 2 B chains Hemoglobin *Each hemoglobin molecule has 4 Fe molecules. One Fe can hold one oxygen at a time. *The primary function of RBC is to transport hemoglobin, which in turn carries oxygen from the lungs to the tissues and the carbon dioxide back from the tissues to the lungs. *97% of oxygen is carried to the tissues in combination with hemoglobin. Only 3% is dissolved in cells. *CO2 may combine with hemoglobin for it to be transported back to the lungs for excretion.

Sickle cell anemia is an abnormality in the B-chain of Hemoglobin upon exposure to O2, the Hgb forms elongated crystals prone to hemolysis or easily ruptures IRON 5 grams in the human body majority is in the form of Hemoglobin (65%) 15 30 percent ferritin (Storage form in the liver) 4% myoglobin (hemoglobin in the muscle) 1% other heme compounds 0.1 with transferrin primary source is red meat Absorption of IRON <Duodenum> 1. Liver produces apotransferrinsecreted into the BILEapotransferrin + Fe Transferrin (plasma) blood transferrin donates Fe to RBCHemoglobin is produced 2. Transferrin I Iexcess Fe Tissues Ferritin Destruction of Hgb RBC ruptures after 120 days Hemoglobin is released and broken down to bilirubin Fe is never wasted. It is liberated and brought back to the iron stores. Women: are prone to IRON deficiency anemia due to menstruation. Should take supplements at least once a day. Anemias are brought about by deficiency of Hgb Too rapid loss / too slow production Blood loss; Fe deficiency

Clinical Correlation: When a patient presents with severe palor (anemia), the physician will usually request for a peripheral blood smear. Result: If the RBCs are microcytic hypochromic, the cause of anemia is IRON DEFICIENCY. If the RBCs are microcytic hyperchromic, the cause of anemia is Vit B12 / FOLIC ACID DEFICIENCY. Aplastic Anemia- is a bone marrow disorder, where all blood cells are not produced Hereditary Spherocytosis- is a situation where the RBCs are spherical instead of bi-concave *Plasma causes oncotic pressure, while RBC renders viscosity to blood. Anemias effect to the heart is INCREASED WORK LOAD. Anemia causes decrease in viscosity of blood; decrease in resistance to blood flow. Thus, more blood goes to the tissues and flows back to the heart. Anemia causes hypoxia. Blood vessels will dilate. Thus, more blood returns to the heart. *Will cause increased heart rate. *Younger individuals can usually tolerate anemia. *Older individuals (60-70) should not be left without treatment because anemia may cause cardiac arrest to individuals with weaker hearts. POLYCYTEMIA nd 2 Degree Polycytemia- ex. Living in high altitudes, smoking, having pulmonary diseases Polycytemia VERA- a genetic aberration; increase in RBC does not inhibit further production of erythropoietin -blood viscosity is increased; resistance to blood flow is increased; blood is prone to clotting episodes -treated by performing phlebotomy BLOOD TYPES TYPE A TYPE B TYPE AB TYPE O A agglutinogens B agglutinogens A and B agglutinogens No agglutinogens B agglutinin A agglutinin No agglutinin A and B agglutinin Agglutination is the end point of transfusion reaction Reaction: <Agglutination> <Hemolysis> AntibodyAntigenRBC will clumpWBCs attack RBC

Immediate Transfusion Reaction IgM immediate hemolysis Delayed Transfusion Reaction a result of secondary immune response BLOOD COMPATIBILITY Donor Cell- refers to the antigen Patients serum- refers to antibody Donors Cell TYPE A Patients Serum TYPE B Result Antigen A Antigen B (Orange) Minor reaction= (+) Antibody B *Blood types are incompatible. Donors Cell TYPE O Antibody A (Red) Major reaction= (+)

Patients Serum TYPE B

Result

Antigen NONE Antigen B (Orange) Minor reaction= (+) Antibody AB Antibody A (Red) Major reaction= (-) *May proceed with transfusion. Patient may suffer slight itchiness as reaction to small amounts of antibodies from Donor cell, which will easily be diluted in Patients blood plasma. *Type O is a universal Donor. Donors Cell TYPE A Patients Serum TYPE AB Result Antigen A Antigen AB (Orange) Minor reaction= (+) Antibody B Antibody NONE (Red) Major reaction= (-) *May proceed with transfusion. Patient may suffer slight itchiness as reaction to small amounts of antibodies from Donor cell, which will easily be diluted in Patients serum. *Type AB is universal recipient. Error in blood transfusion may result in: Agglutination Destruction of RBC membrane by phagocytosis or antibodies Hemolysis =Jaundice Severe hemolysis/decreased amt. of RBCcirculatory shockredistribution of blood to more important organs, ex. Brain Kidneys are bypassedRenal vasoconstrictionhemolyzed cells flow to the kidneys and block the renal tubulesRENAL SHUTDOWN RH BLOOD GROUP-antigens are C, D, E, c, d, e Rh (+)---- the sign is shown on the blood type. Example: A+ means Blood type A and RH (+) The most important factor is the result of the D antigen. Rh antigens are not immediately developed after blood transfusion from RH (+) to RH (-). It takes 2-4 months. After developing antigen, subsequent transfusions will be fatal. Rh (-) to Rh (+) transfusions do not result in undesirable reaction.

Erythroblastosis Fetalis (HDN) st 1 CASE Mother is Rh (-) and Father is Rh (+) Baby Rh (+) Babys blood mixes with mothers blood Mother will develop anti-Rh IgG Mothers anti-IgG will attack the fetal RBC Baby suffers from fetal anemia (Babys heart may fail) Blood backflows; increases capillary hydrostatic pressurehydrops, ascites, pleural effusion, and scalp edema. Spleen and liver are enlarged There will be blasts in the peripheral smear because immature cells are secreted (erythroblastosis fetalis) Increased hemolysis of blood resulting in high bilirubin levels Bilirubin accumulates in the brain (kernicterus) Commonly the baby dies (prevention is better than cure) Treatment to Hydrops: Exchange transfusion o Rh (+) blood is removed during birth also to remove the antibodies, then replaced with Rh (-) blood to stop interaction of antibodies with (+) o Then the baby is allowed to produce its own Rh (+) blood Rho-gam (Rh immunoglobulin) o Rho-gam will coat the fetal RBC so that the maternal blood will not identify it and will not produce antibodies th th o Rho-gam is administered on the 28 week or 7 month (during which time the mothers blood mixes with the babys) *First baby is not affected because the sensitization will take several months. st *Rho-gam should be given on the 1 pregnancy to prevent mothers sensitization. *Only IgG can penetrate the placenta because of its small size. nd 2 CASE Mother is Rh (+) and Father is Rh (-) Baby Rh (-) The baby and the mother are unaffected because no reaction will occur. The baby cannot produce antibodies during this stage. Prepared by: M.A. Pamular