Red Blood cell Disorders Flashcards
What is anemia? How does it present? What is used to measure it? Normal Hb measures? What is microcytic, normocytic, and macrocytic?
Reduction is circu. RBC mass
Weakness, fatigue, dyspnea
pale conjunctiva and skin
headache and lightheadedness
Hb (13.5-17.5 in males, 12.5 to 16.0 in females), Hct, and RBC count.
Normocytic=80-100
What causes microcytic anemias? What is hemoglobin made up of? What are some examples?
Decr. production of hemoglobin
Heme (protoporphyrin and iron) and globin
iron deficiency anemia, anemia of chronic disease, sideroblastic anemia, and thalassemia
What causes iron defic? What are the 4 stages of iron deficiency? Clinical features? Lab findings? Treatment? What is plummer vinson syndrome?
Dietary lack or blood loss: Infants (breastfeeding low in iron) Children (poor diet) PUD in males and menorrhagea in females Colon polyps/CA in elderly; hookworm Malabsorption Gastrectomy
Storage iron is depleted (Decr. Ferritin, Incr. TIBC)
Serum iron is depleted (decr. serum iron, decr. % satur.)
Normocytic anemia=fewer, but normal RBCs
Microcytic hypochromic anemia
Anemia, koilonchia, and pica
Microcytic hypochromic RBCs with Incr. RDW
Decr. ferritin, incr. TIBC, decr. serum iron, decr. % sat.
Incr. free erythrocyte protoporphyrin
Supplemental iron
PLummer vinson: Esophageal web (dysphagia), atrophic blossitis (beefy red tongue), iron def. anemia
What is the pathophys of anemia of chronic disease? Lab findings?
In chronic disease, acute phase reactants including hepcidin are increased.
Hepcidin sequesters iron in storage sites (helps ferritin) by limiting transfer to erythrocytes and suppressing EPO.
Incr. ferritin, decr. TIBC, decr. serum iron, decr. % sat.
Incr. free eryth. protoporph.
What is the pathophys of sideroblastic anemia? Describe the production of protoporphyrin including relevant substrates, products and enzymes. What is a congenital cause? Acquired causes? Lab findings?
Defective protoporphyrin synth. Iron is transferred to erythroid precursors and enter mitochondria but if protoporphyr. isn’t there, it forms a ring around the nucleus of RBCs (ringed sideroblasts)
Glycine and succinyl Coa are converted to Aminolevulinic acid (aminolevulinic acid synthase (B6)-sideroblastic anemia) to porphobilinogen (ALAD-lead poisoning) and eventually to protoporphyrin (AIP and Porphyria cutanea tarda) which enters the mitochondria and is converted to heme by receiving iron (ferrochelatase-lead poisoning)
Congenital (ALAS defic.)
Alcoholism-mitochondrial poison
lead poisoning
vit. B6 deficiency
Incr. ferritin, decr. TIBC, incr. serum iron, incr. % sat
What is the affected enzyme in lead poisoning? What substrate is built up? Where? What is seen on blood smear? What other symptoms are there for adults and for children? How are adults and children exposed?
ALA dehydratase, Ferrochelatase
Protoporphyrin, ALA (blood)
Basophillic stippling, GI, kidney disease in all
Children: lead paint, mental deterioration
Adult: batteries, ammunition; headache memory loss, demyelination
Waht is the affected enzyme in acute intermittent porphyria? Substrate buildup? What are the symptoms? What is the treatment? Mechanism?
porphobilinogen deaminase
porphobilinogen, ALA, coporphobilinogen (urine)
Painful abdomen port-wine colored urine polyneuropathy psych disturbance precipitate by drugs, alcohol, starvation
glucose and heme-prevent synth of ALA
What is the affected enzyme in porphyria cutanea tarda? Substrate build up? symptoms?
uroporphyrinogen decarboxylase
uroporphyrin (tea colored urine)
Blistering cutaneous photosensitivity
What is thallassemia? What are the normal types of hemoglobin?
Decreased synth of globin chains of hemoglobin
HbF (alpha 2 gamma 2) HbA (alpha 2 beta 2) HbA2 (alpha 2 delta 2)
What cuases alpha thallassemia? How many alpha genes are present? On which chrom? What happens if one gene is deleted? Two genes (clinically)? What is a cis and trans deletion? In which populations do they occur? Clinical implications? What happens when 3 genes are deleted (pathophys and clinical)? 4 genes (pathophys and clinical)?
gene deletion; 4 genes on chrom. 16
One gene-asymptomatic
two genes-mild anemia with incr. RBC count
Cis=both deletions on same chromosome (asian)
Trans-one deletion on each chromosome (afr. americans)
Cis leads to incr. risk of passing on severe thalassemia
3 genes-Severe anemia-beta chains form tetramers (HbH) that damage RBCs; HbH on electropheresis
4 genes-hydrops fetalis. Gamma c hains form tetramers (Hb barts) that damage RBCs
What causes beta thalassemia? Epidemiology? Which chromosome? What are beta 0 and beta + mutations? What mutations occur in beta thalassemia minor? Clinical findings? Blood smear? What is seen on hemoglobin electrophoresis? What mutations occur in beta thalassemia major? How does it present? Pathophys? Clinical findings? What are they at risk for? Treatment? Blood smear? What does electrophoresis show?
Point mutation on chromosome 11 (two beta genes)
mediterranean and african descent
Beta +-diminished production
beta 0=absent produciton
Minor: beta/beta + is asymptomatic wiht incr. RBC count
Microcytic hypochromic anemia with target cells
Electrophoresis shows slightly decr. HbA with incr. HbA2 and HbF
Major: beta0/beta0 is severe anemia a few months after birth (after HbF wears off)
Unpaired alpha chains damage RBC membrane leading to ineffective erythropoesis and extravascular hemolysis
Massive erythroid hyperplasia with hematopoesis in skull (CREWcut appearance) and facial bones (chipmunk), HSM, risk of aplastic crisis with parvovirus B19
Chronic transfusions
Smear: microcytic hypochromic RBCs with target cells and nucleated RBCs
HbA2 and HbF with little HbA
What is macrocytic anemia? Main Causes? Other causes? Pathophys of main causes?
Anemia with MCV > 100.
Folate of B12 defic (megaloblastic anemia)
Alcoholism, liver disease, drugs
Decr. folate and b12 leads to impaired synth of DNA precursors leading to impaired division and enlargement of RBC precursors leading to megaloblastic anemia.
Also leads to imparied division of granulocytic precursors leading to hypersegmented neutrophils
Also see in rapidly diving epithelial cells
Where does folate come from? Where is it absorbed? How quickly does it develop? CAuses? Clinical and lab findings?
Green vegetables and some fruits
jejunum
poor diet, incr. demand and folate antagonists
Macrocytic RBCs with hypersegmented neutro glossitis decr. serum folate incr. homocysteine normal methylmalonic acid
Describe the absorption of vit. B12. What are some causes of defic. How long until it develops? Clinical and lab findings?
Salivary gland enzymes liberate Vit. b12 which then binds to R-binder where its carried through the stomach.
In the duodenum, pancreatic proteases detach it from R-binder.
It the binds intrinsic factor (made by gastric parietal cells) in small bowel.
This complex is absorbed in the ileum
Years to develop
Pernicious anemia, pancreatic insufficiency, damage to ileum
Macrocytic RBCs w/ hypersegmented neutro glossitis subacute combine degeneration of spinal cord (Incr. methylmalonic acid (can't convert it to succinyl coa) leading to poor proprioception, vibratory sensation and spastic paresis Decr. vit. B12 Incr. homocysteine
What is normocytic anemia? What are the two basic causes? How can they be distinguised? What are reticulocytes? How do they look on smear? What is a normal count? How does normally functioning marrow respond to anemia? How is this corrected? What does this number mean?
MCV=80-100
Incr. periph. destruction or decr. produciton
Reticulocyte count can differentiate
Reticulocytes are young RBCs released from bone marrow (larger cells with bluish cytoplasm)
Normally, the count is 1-2%. In anemia, the number will be raised to more than 3%, but this number must be corrected in anemia by multiplying it by Hct/45.
Corrected count greater than 3 indicates good marrow response (periph. destruction)
