Pathoma - 5 (RBC Disorders)

ridivubu's version from 2016-03-29 18:43

Section 1

Question Answer
what Hb level defines anemia in males?Hb <13.5
What Hb level defines anemia in females?Hb < 12.5 g/dL
what is heme composed of?iron and protoporphyrin
what type of anemia is anemia of chronic disease?microcytic anemia
what type of anemia is sideroblastic anemia?microcytic anemia
what type of anemia is thalassemia?microcytic anemia
what anemia is characterized by low protoporphyrin?sideroblastic anemia
what anemia is characterized by decreased production of globin chains?thalassemia
what anemia is characterized Fe+2 not available for use since its stored in macrophages??anemia of chronic disease

Section 2

Question Answer
where does iron absorption occur?duodenum via DMT1 transporters on enterocytes
what is iron bound to in the stored form?ferritin
whats the role of transferrin?transferrin transports iron in the blood and delivers it to the liver and bone marrow macrophages for storage
what does TIBC measure?measure of transferrin molecules in the blood - whether bound or not by iron
what does %sat measure?percentage of TRANSFERRIN molecules that are bound by iron (normal = 33%)
what does serum ferritin measure?iron stores in macrophages and liver
whats a cause of iron deficiency in newborns?breast-feeding (breast milk is low in iron)
whats a cause of iron deficiency in adult men?peptic ulcer disease
what a cause of iron deficiency in the eldery?colon polyps/carcinoma or Ancylostoma/Necator hookworms
how does gastrectomy cause iron deficiency?gastric acid helps iron absorption by maintaining the Fe+2 state which is more readily absorbed than Fe+3
why do you see an increase in TIBC when theres decreased ferritin?when ferritin is decreased, the liver pumps out more transferrin to find circulating Fe+2
what does serum ferritin measure?how much iron is actually in storage sites --> bone marrow, macrophages, liver
Initial stage of iron deficiency anemia shows what kind of anemia?NORMOCYTIC anemia
whats koilonychia?spoon shaped nails = feature of iron def anemia
whats pica?chew on weird things to see iron = feature of iron def anemia
what weird lab value is seen in iron deficiency anemia?increased free erythrocyte protoporphyrin (FEP) = in RBC there will be some FEP due to decreased and unbound iron

Section 3

Question Answer
anemia characterized by decreased available iron?anemia of chronic disease
what acute phase reactant keeps iron in storage sites so it cant be used?Hepcidin
which 2 anemias first have a normocytic anemia before microcytic anemia?iron deficiency anemia and anemia of chronic disease
anemia due to defective protophorphyrin synthesis?sideroblastic anemia
iron laden mitochondria form a ring around the nucleus of RBC precursors?ringed sideroblasts
what congential defect causes sideroblastic anemia?deficiency in ALAS (converts succinyl-CoA to ALA)
name 3 acquired causes of sideroblastic anemia?alcoholism (poisons mitochondria)
lead poisoning (inhibits ALAD and ferrochelatase)
vit B6 defiency (cofactor for ALAS)
in sideroblastic anemia, where is iron located?iron is trapped in the mitochondria which surrounds the nucleus
isoniazid causes what type of anemia?sideroblastic anemia (decreases vit B6)
lab findings show iron-overloaded state?sideroblastic anemia

Section 4

Question Answer
what is HbH composed of?beta chains form tetramers (HbH) that damage RBCs
what is Hb Barts composed of?gamma chains form tetramers which damage RBCs
what does 4 alpha gene deletions cause?hydrops fetalis in utero
which chromosome holds the 4 alpha genes?chromosome 16
which chromosome holds the 2 beta genes?chromosome 11
target cells?thalassemia anemia
crewcut appearance of skull of xray suggest?s?expansion of hematopoesis into the skull = sign of thalassemia
chipmunk facies?expansion of hematopoesis = sign of thalassemia

Section 5

Question Answer
folate deficiency vs. vit B12 deficiency?folate defieciency = NORMAL methylmalonic acid
Vit B12 = INCREASED methylmalonic acid
where is folate absorbed?jejunum
what type of anemia is associated with methotrexate use?folate deciency --> macrocytic anemia
what vitamin converts methylmalonic acid to succinyl-CoA?Vit B12
how long does it take to develop folate deficiency? vit B12 deficiency?folate deficiency = months. Vit B12 deficiency = years due to large liver stores of vit B12
why does pancreatic insufficiency cause vit B12 defiency?pancreatic insufficiency --> decreased pancreatic proteases which normally cleave vit B12 free from R-binder
what type of anemia is associated with Crohns disease?vit B12 deficiency --> damage to terminal ileum
how does a pt with vit B12 deficiency get subacute combined degeneration of the spinal cord?due to increased methylmalonic acid built up and deposited in the myelin of spinal cord
what enzyme cleaves vit B12-R binder?pancreatic proteases

Section 6

Question Answer
what are 2 causes of normocytic anemia?due to increased peripheral RBC destruction or underproduction
whats the formula for CORRECTED Reticulocyte Count?Corrected RC = RC x (Hct/45)
corrected count >3% indicates?good marrow response and suggests peripheral destruction
corrected RC <3% indicates?poor marrow response and underproduction
what does protoporphyrin break down into?unconjugated bilirubin
what is responsible for extravascular hemolysis?macrophages of the liver, spleen, and LNs
why do we see hemosiderinuria in intravascular hemolysis?renal tubule cells pick up some of the Hb that is filtered into urine and break it down into iron, where it accumulates as hemosiderin --> tubular cells are shed --> hemosideruria
why do we see decreased haptoglobin in intravascular hemolysis?decreased FREE haptoglobin since it binds to leaked out Hb
what are howell jolly fragments?fragments of nuclear material in RBC = sign of splenic dysfunction or removal
what causes hereditary spherocytosis?defect of RBC cytoskeleton-membrane tethering proteins = spectrin, akyrin, band 3.1
what virus infects RBC eyrthroid precursors?parvovirus B19

Section 7

Question Answer
what amino acid change is seen in sickle cell anemia?glutamic acid (hydrophilic) --> valine (hydrophobic) in beta chain of Hb
what increases the risk of RBCs sickling?hypoxemia, dehydration, acidosis
whats the tx of sickle cell anemia?hydroxyurea = increases levels of HbF (HbF protects against sickling)
whats a common presenting sign in infants of irrervsible sicking/vaso-occlusion?dactylitis = swolling hands and feet due to vaso-occlusive infarcts in the bones
what org causes osteomyelitis in sick cell pts?salmonella paratyphi
whats the most common cause of death in adult sickle cell pts?acute chest syndrome = vaso-occlusion in pulmonary microcirculation
what does metabisulfite screen for?causes cells with any amount of HbS to sickle --> identifies sickle cell trait or disease
how do you confirm the diagnosis of sickle cell disease?Hb electrophoresis for presence/amount of HbS
what aa change is seen in the beta chain of Hemoglobin C?normal glutamic acid replaced with LYSINE (also has rod-shaped crystals)

Section 8

Question Answer
Whats the defect associated with PNH?defect in myeloid stem cell --> absent glycosylphosphatidylinositol (GPI)
What causes PNH?absence of GPI --> no DAF or MIRL --> RBCs are susceptible to complement mediated damage by C3 convertase
Which cells are lysed in PNH?RBC, WBC, platelets are all lysed since they all normally contain GPI
What is the screening test for PNH?sucrose test = activates complement
Name 2 confirmatory tests for PNH?acidified serum test (to activate complement) or flow cytometry to detect lack of CD55 (DAF) and CD59 on blood cells
whats the main cause of death in pts with PNH?THROMBOSIS of hepatic, portal or cerebral veins --> destroyed platelets induce thrombosis
Name 2 complications of PNH?iron deficiency anemia and AML
Heinz bodiesG6PD deficiency
How does G6PD defiency lead to intravascular hemolysis?decrease G6PD --> decreased production of NADPH --> decreased reduced gluthathione --> oxidative injury by H202 --> INTRAVASULACR HEMOLYSIS