NU608 Anemia and Polycythemia.pdf

“Hmmmm” I couldn’t find this problem in any of my patho books  1 The mature RBC, the erythrocyte, is a non-nucleated, biconcave disk that contains no nucleus, mitochondria, or ribosomes. It cannot reproduce or undergo oxidative phosphorylation. The shape of the RBC increases the surface area availa...

“Hmmmm” I couldn’t find this problem in any of my patho books  1 The mature RBC, the erythrocyte, is a non-nucleated, biconcave disk that contains no nucleus, mitochondria, or ribosomes. It cannot reproduce or undergo oxidative phosphorylation. The shape of the RBC increases the surface area available for diffusion of oxygen and allows cell to change in volume & shape without rupturing its membrane…all, so that the RBC can perform its function…transport oxygen to tissues Lifespan of the RBC 120days in adults 90 days in infants and as short as 2 -10 days in some hemolytic anemias (such as sickle cell disease) 2 RBC production: Erythropoeisis is the production of red cells At birth all RBCs are produced in the red bone marrow all bones produce red cells up until about 5 years of age and then the red marrow is slowly replaced by fatty yellow bone marrow. After 20 years of age – red cell production takes place in bones of vertebra, sternum, ribs, pelvis (red marrow replaced with fatty yellow bone marrow) Red cells are derived from erythroblasts which are formed continuously by stem cells in the bone marrow. In developing to a mature cell  the red cell precursors move thru a series of divisions each producing a smaller cell. During its transformation to a “mature” cell– the red cell accumulates hgb as the nucleus condenses and is finally lost Most maturing red cells enter the blood as reticulocytes and then continue to mature to the erythrocyte. Approximately 1% of the body’s total complement of RBC is generated from the bone marrow each day. The reticulocyte count is a good index of the erythropoeitc action of the bone marrow. Reticulocytes are immature red cell precursors, and normally account for about 1-2% of the RBCs in circulation. If RBC death is excessive, a larger than normal amount of immature red blood cells, the reticulocytes, will be released from the bone marrow; elevated levels of circulating reticulocytes are suggestive of certain types of anemia. The retic count is useful for evaluating anemia. Some of the anemias are caused by blood loss (hemorrhage, hemolytic anemias), whereas others are due to difficulties in synthesizing RBCs (iron, B12 or folate deficiency, loss of EPO, or bone marrow failure). **important*** If RBC count is low – the appropriate response is to increase RBC production, which will increase the reticulocyte count. So, a normal or low retic count in the presence of anemia signifies that there is a problem with RBC production (for example – iron, B12 or folate deficiency. A high retic count can only occur if the anemia is NOT a problem of production. So, the combination of anemia and an elevated retic count suggests RBC loss is causing the anemia – either from hemorrhage or hemolytic anemia. **Circle, star and underline  the info on the retic count. 3 Erythropoeisis is governed for the most part by tissue oxygen needs: Oxygen content of blood doesn’t act on the bone marrow directly… Instead, the decreased oxygen content is sensed by kidney The kidneys then produce the hormone  erythropoietin Erythropoietin then acts on the bone marrow to stimulate RBC production 4 What do you think  5 6 The hemoglobin consists of an iron-containing substance called heme and the protein globulin. There’s ~ 300 hgb molecules in each RBC. The heme molecule is composed of 2 pairs of structurally different chains determined by genes. Alterations in genes result in abnormal hgb. The two major types of normal hgb are: Adult hgb (hgbA)  pair of alpha & beta chains Fetal hgb (hgbF)  has a pair of gamma chains substituted for beta. Fetal hgb converts to adult hgb ~ 4-6months of age Each of the 4 polypeptide chains is attached to a heme unit - Which surround an atom of iron that binds oxygen - Four molecules of oxygen can be carried by one hgb molecule Genetic mutations can cause hgb protein to form incorrectly (ie – sickle cell) or cause inadequate amounts of alpha or beta chains (thalasesemia) to be formed – either of which can cause anemia. 7 Another question  8 9 RBC survival depends on having a(n): Intact bone marrow (a bone marrow that respond to the stimulation of erythropoietin) Functional erythropoietin (kidney has to be able to produce erythropoietin) Uncompromised DNA (need components of folic acid and vitamin B12) Uncompromised Hgb synthesis (need iron and globin) 10 RBC destruction: when the RBC begins to disintegrate at the end of its lifespan, it releases hemoglobin into the circulation. Hgb is broken down in the liver and spleen Hgb broken into iron and globin  which are salvaged and reused The rest is converted to bilirubin, which is excreted in the stool as bile or in the urine. Normally , the rate of destruction (1% per day) is equal to the amount produced each day. 11 Laboratory Tests in evaluating the red cells RBC  number of red blood cells (4.2-5.4) millions Reticulocytes  provides an index of the rate of red blood cell production (normal is approximately 1-2% of total RBCs) Hemoglobin (grams per 100ml of blood)  measures the hgb content of the blood (13.5-17.5 g/dl for men; 12-16 g/dl for women) The major components of blood are the RBC mass and plasma volume. The percentage of the blood that is taken up by red blood cells is called the hematocrit, which usually ranges from ~36 -50% depending on age and sex (41-50% for men; 3646% for women) 12 Red cell indices are used to differentiate types of anemia by size and color of red cells. They are described clinically by their size and by the amount of hemoglobin present in the cell. The suffix “cytic” refers to the size, and the suffix chromic” refers to the concentration of hemoglobin in the cell (as it’s the hgb that gives the cell its color). Mean corpuscular volume (MCV) reflects the volume (or size) of the red cells; the MCV is the most commonly used index for identifying whether a cell is of normal, small, or large size and is used clinically to categorize an anemia: normocytic: cells of normal size (MCV 87-103 fl/red cell) microcytic: cells too small in size (MCV 103) Mean corpuscular hgb concentration (MCHC)  concentration of hgb in the RBC (normal MCHC 31-35 g/dl) Hgb accounts for the color of red blood cells Normochromic anemias (have normal color or MCHC) Hypochromic: cells with too little hgb  decreased color or MCHC Hyperchromic: cells with too dense hemoglobin FYI  MCHC cannot be greater that 37 g/dl as the RBC cannot accommodate more than 37 grams – so, if you see a MCHC greater than 37 you need to have the lab check for errors in the conctration of hgb determination. The Fischback lab manual has a nice review (pg 96-103; 106-107) 13 ANEMIAS Not a disease, but an indication of some disease process or alteration in body function that is resulting in a deficiency in red cells or hgb. This can be the result of: Excessive loss  blood loss  loss of iron-containing cells from body Increased destruction  hemolytic  destruction of RBC with iron retained in the body Impaired production of the RBC iron-deficiency, megaloblastic anemias (B12 or folate deficiency), aplastic anemias World Health Organization (WHO) defines anemia as: Men  hemoglobin < 13.0 gm/hematocrit < 42% for men Women hemoglobin