| How are red cell disorders? | Some of the most common diseases, anemia can result from many conditions (iron deficiency, Hbpathies, chronic infection)
Hemolytic anemia occurs w/red cell lifespan is reduced, increased nb of red cells are seen in polycythemia (myeloproliferative disease in response to hypoxia)
Anemia is very common worldwide |
| What is anemia? | Reduction in Hb levels in blood, must take into consideration age and gender (above 18 males normal [13,14.5], females [12,14], under 18 each age group has values at birth high, decreases at 1 months, and starts increasing after 2 months)
Symptoms of anemia (tiredness, SoB, poor concentration, palpitations, pallor) |
| How are classifications of anemia by MCV? | Microcytic (MCV<80) seen in iron deficiency, thalassemia.
Normocytic (80-95) seen in chronic infection, renal disease, marrow disease
Macrocytic (MCV>95) seen in hemolytic anemia, vitamin B12 and folic acid deficiency |
| How is iron physiology? | Metabolism (absorption regulated highly preventing toxicity, no pathway of excretion of excess iron, can be toxic in excess damage DNA)
Body iron compartments (Hb (Males 2.5g, females 1.9g), myoglobin less (300mg), enzymes less (180mg), transferring much less (2.7mg), ferritin and hemosiderin (800 mg male 300 mg female), total in female 2.7g in male 3.8g)
70% stored in Hb, 25% in reticuloendothelial system (ferritin, hemosiderin), 5% myoglobin, cytochromes, enzymes and <1% transferrin in plasma
Absorption is in upper small intestine (after gastric secretion convert them into Fe2+), most are not absorbed, some go in intestinal mucosa make ferritin and are excreted after shedding 1mg iron, only iron needed for erythropoiesis is absorbed into blood by hepatocyte 1mg/day bound to transferrin. |
| How is iron absorption in small bowel regulated? | Enhanced absorption (seen in iron deficiency, increase erythropoiesis, dietary factors are ascorbic acid (Vit C) and heme vs. nonheme Fe)
Inhibited absorption (seen in increased iron stores, cause inflammation, dietary factors are tannins (tea) and phytates (bran))
Regulation of metabolism by hepcidin (which increases Fe storage in macrophages and decrease it in blood and absorption by hepatocytes by binding ferroportin on macrophages and enterocytes degrade them, increased activity in case of inflammation and increased Fe, decreased in case of increased hemopoiesis and Fe deficiency |
| How is heme biosynthesis by immature red cells? | In mitochondria (glycine and succinyl CoA acted on by ALA synthase and vitamin B6 to form ALA, which will become protoporphyrin, which combines w/ iron from ferritin or transferrin coming from cytosol to become Heme)
In cytosol (Globin chains are formed by translation, combines w/ heme to make hemoglobin tetramer) |
| What is iron deficiency? | Most common finding in people around the globe, major cause is chronic blood loss through menstruation, GI blood loss (malignancy/inflammation), if no obvious cause of bleed check other causes (dietary insuff, malabsorption)
Tx (oral iron, IV iron can be given for intolerant people/ malabsorption cause) |
| What is sideroblastic anemia (SA)? | Group of inherited and acquired anemia, iron accumulates in mitochondria of erythrocyte precursors.
Inherited (X recessive, more in males, abnormality synthesis of protoporphyrin decreased Hb, iron accumulated cause ring sideroblast, iron laden mitochondria ring around nucleus of RBC precursor in bone marrow, basophilic stippling in peripheral smear (no2at)), Acquired (alcoholism, B6 deficiency, lead poisoning, Cu deficiency, age>74) |
| What is thalassemia? | Other major cause of microcytic anemia, imbalance of a and b globin, a deficiency in a (deletion), b defect b chain (mutation), tx blood transfusion.
a thalassemia (more in asian, maybe minor (2/4 alleles affected mild microcytic anemia), HbH disease (3/4 affected, cause chronic hemolytic anemia, lead to beta tetramer (HBH) and Bart'sHbG increase in electrophoresis), hydrops fetali (4/4 alleles affected, total body edema fetal, barts Hgb high)
Beta thalassemia (more in MENA, required at six months (may be minor (asymptomatic, decreased HbA increased A2 and normal F, tx avoid oxidative stress) or major (anemia at six months, no HbA, increased A2 and F, splenectomy tx, folate supplement, transfusion , may die due to transfusion iron overload)
We see decreased Hb and MCV and normal or increased RBC count (Mentzer ratio= MCV/RBC if less than 13-> thalassemia if more iron deficiency or inflammation. |
| What are some findings in thalassemia? | Skull radiography of child w/beta thalassemia we see massive expansion of hemopoiesis w/in bone marrow (even skull) so leads to hair on end appearance on skull Xray.
We may see hepatosplenomegaly due to extramedullary hemopoiesis.
If regular transfusions are given iron chelation is a must to avoid iron poisoning. |
| Table of iron def anemia, chronic disease anemia, thalassemia and SA. | . |
| What is normocytic anemia? | Chronic inflammation (iron sequesters in macrophages, reduce iron levels w/no increase in iron binding capacity, tx of underlying disease)
could be renal disease (kidney produce EPO suppressed by kidney damage, so give EPO injection for CKD pt)
Could be bone marrow disease (reduced RBC, WBC and platelets, can't produce normal cells, infiltration w/leukemia, myeloproliferative disease, infiltration w/carcinoma/aplastic anemia) |
| What is macrocytic anemia? | large erythroblasts (megaloblast), multilobed nuetrophils, due to deficiency of vitamin B12 or folate
Pernicious anemia (autoimmune Ab against gastric parietal cells and intrinsic factor prevent B12 absorption in terminal ileum, neuropathy can occur lead to numbness and if severe blindness or dementia, tx vitamin B12 PRL)
Folate deficiency (when we have excess need for folate like pregnancy/hemolytic anemia, give folic acid tablets |
| What is hemolytic anemia? | Shortened half life lead to increasing reticulocytes, which are larger than RBC (increase MCV), lifespan may go below 15 days then develop anemia.
Classified into inherited (Red cell mmb, cytoskeleton, Red cell enzymes, Hb) and acquired (autoimmune, PNH, infection...) |
| How is Hb catabolism? | . |
| What is hereditary spheocytosis? | Abnormality in gene of spectrin (ankyrin protein band 3.0 and 4.1)
Red cell is smaller and more dense than usual, tx folic acid and when necessary splenectomy, other examples are hereditary elliptocytosis (mutation in spectrin/ankyrin/band 3/band 4.1/4.2 defects impair elastic deformability of RBC lead to spherocytic shape of RBC (not biconcave disc)
We see MCHC >36 (CBC), smear see spheocytes and some polychromatophilia (reticulocytosis), increased LDH and bilirubin, decreased haptoglobin, elevated reticulocyte count (in hemolysis testing), Coombs test negative (not autoimmune)
Confirmatory test (EMA binding (eosin-5-maleimide, binds membrane proteins of RBC), or osmotic fragility test (OFT) |
| What is pre-splenectomy vaccination done for HS? | Immunization for encapsulated organisms should be given (vaccine for pneumococcal disease, hemophilus influenza, meningococcal diseases) |
| What is G6PD deficiency? | More common in MENA, since if heterozygous provide protection against malaria, Xlinked (avoid oxidants), other examples Pyruvate kinase.
Lack of sufficient G6PD leads to oxidation damaging RBC due to inadequate NADPH (prevents oxidative stress by reducing glutathione by glutathione reductase).
HMP shunt is the way of producing NADPH, leading to reduced glutathione, detoxify peroxidase and free radicals w/in RBC preserving RBC membrane integrity.
So in G6PD deficiency we see hemolysis, and reticulocytes appear w/in 5-10 days, and have G6PD activity to compensate the loss, so ends the anemia w/in a week (self limited)
Tx (remove inciting agent of hemolysis, maybe aggressive hydration for acute intravascular hemolysis/transfusion for severe anemia), chronic hemolysis give folic acid
Test (first resolve hemolysis then test, used for people in need for oxidant drug |
