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124 Cards in this Set
- Front
- Back
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How does human body compensate anemia?
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- increase cardiac output
- shift O2-Hb dissociation curve - increase EPO: increase reticulocytes - bone marrow expansion into fatty spaces, may cause bone deformity if longterm and if in young kids. |
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Internal or external bleed?
iron recaptured |
internal
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After acute blood loss, how long does it take to equilibrate?
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1-3 days
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After acute blood loss, when does bone marrow reponse peak during restoration process?
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7 days
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Explain the restoration process after acute blood loss.
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- leukocytosis: granulocyte mobilized from marginal pool
- water shift from interstitial fluid compartment - low Hct, oxygenation - EPO release (kidney) - CFU-E proliferation (bone marrow) |
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Chronic blood loss usually manifest as ____.
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iron deficiency
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What type of anemia is this?
- shortened RBC lifespan - elevated EPO - erythroid precursors in bone marrow - retilucocytosis in peripheral blood |
hemolytic anemia
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What are some complications of hemolysis?
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- anemia
- aplastic crisis (parvovirus infect stem cells) - folic acid deficiency(megaloblastic anemia): chronic hemolytic anemia should receive daily folic acid. - skeletal deformity:"hair on end" appearance on X-ray. - gallstones: pure bilirubin - Fe overload (extravascular hemolysis only) - DIC (intravascular hemolysis only and complement activation) - Kernicterus: bilirubin deposits in basal ganglia |
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This causes intra- or extra-vascular hemolysis?
- mechanical injury defective cardiac valves thrombi |
intravascular
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This causes intra- or extra-vascular hemolysis?
- severe G6PD |
intravascular
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This causes intra- or extra-vascular hemolysis?
- mutations in PIGA which is essential for GPI anchor |
PNH: intravascular hemolysis
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Which types of anemias are intravascular?
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- severe G6PD
- mechanical trauma - PNH - acute blood loss (can also be extravascular) |
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What condition may trigger symptoms in HS patients?
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- parvovirus infection
- infectious mono - gallstones |
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Why is MCH elevated in HS?
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loss of Na and H2O
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What is this disease?
- elevated reticulocytes, indirect bilirubin, RDW - decreased RBC level, haptoglobulin - positive osmotic fragility test |
- HS: ankyrin mutation
- HE: band 3 protein mutation |
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How do you treat HS and HE?
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Splenectomy after age 5.
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What is this disease?
- X-linked - hexose monophosphate pathway involved - morphology: bite cells, heinz bodies |
G6PD
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What are some triggers of crisis in G6PD?
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Oxidative stress
- infections: viral hepatitis, pneumonia, typhoid fever - drugs: antimalarial, sulfonamide, nitrofurantoins - fava beans |
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What diseases are protective against malaria?
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- G6PD
- HbS - alpha thalassemia |
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What diseases/conditions would you think of when you see Heinz bodies on a blood smear?
How to differentiate them apart? |
- G6PD: will also see bite cells
- lead poisoning: decreased ALA synthase and dehydrase in Hgb synthesis -> will also see ribosome aggregation. |
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What is this disease?
- glycolytic pathway abnormality - AR transmission - reticulocytes and poikilocytes |
PK deficiency: chronic hemolytic anemia.
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Why does patients with PK deficiency have greater tolerance to anemia?
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decreased ATP production -> 2,3 DPG accumulation -> O2-Hgb curve shift to the right -> give off O2 more easily.
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What is this disease?
- hand-foot syndrome - pain crisis - pigmented gallstone - leg ulcer - vision loss |
sickle cell anemia
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What are some factors for cell sickling? Which is the most important?
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- interaction of HbS with other Hgb chains: most important
- MCHC: alpha thalassemia lowers MCHC which lowers the sickling - low pH: lowers O2 affinity, facilitates sickling - long transit time: facilitates sickling - amount of Hb in plasma: inactivates NO, increases vascular tone, facilitates sickling |
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What should you give HbS patient prophylactively? and for what reason?
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Penicillin for infection with encapsulated organism because of autosplenectomy and impaired alternative complement pathway(impaired opsinization).
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Why do patients with HbS have enlarged spleen as a kid and spleen atrophy at older age?
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As a kid: spleen sequestration of defective RBCs
Later on: vaso-occlusive events cause hypoxia/infarction of the spleen, which leads to fibrosis and atrophy of the spleen. |
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Why do patients with HbS have screw-cut skull or prominent cheek bones?
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bone marrow hyperplasia -> bone resorption -> 2nd bone formation
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What is the treatment for sickle cell anemia? and what is the drug mechanism?
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Hydroxyuria:
- increases HbF - anti-inflammatory - increase RBC volume - oxidized by heme to produce NO |
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What is this drug?
- increases HbF - anti-inflammatory - increase RBC volume - oxidized by heme to produce NO |
hydroxyuria
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What is the genetic mutation for HbS?
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glutamic acid -> valine at 6th position on beta chain
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What is the genetic mutation for HbC?
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glutamic acid -> lysine at 6th position on beta chain
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What is this disease? be specific.
- morphology: target cells Hgb crystals |
HbSC
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What is this disease? be specific.
- morphology of RBC: normal - painless hematuria |
Sickle cell trait
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What is the most reliable diagnostic test for sickle cell anemia?
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Hb electropheresis
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What is the genetic difference in pathogenesis of alpha and beta thalassemia?
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alpha thalassemia: deletion on chromosome 16
beta thalassemia: mutation (most commonly splicing sites) on chromosome 11 |
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What is this disease?
- hypochromic, microcytic,basophilic stipling - aniscocytosis, poikilpcytosis - target cells - marked increase in HbA2 and HbF |
beta-thalassemia
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What is this disease?
- increase in Fe, ferritin - decrease in TIBC |
beta-thalassemia
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What is this disease?
- normal Fe+ - increase ferritin - decrease in TIBC |
beta-thalassemia trait
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How to treat thalassemia?
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- iron chelator for iron overload
- HLA matched bone marrow transplant |
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What are some complications of beta-thalassemia major?
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- iron overload -> cardiac disease
- hemosiderosis, 2nd hemochromatosis - prominent facial bones, sparing of the mandible. |
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Which type alpha-thalassemia is completely asymptomatic?
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silent carrier state: single alpha-globin gene mutation.
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What is this disease?
- minimal or no anemia - microcytic - asymptomatic - Hb eletrophoresis look normal |
alpha-thalassemia trait
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What is this disease?
- more common in Asian - moderate anemia - resemble beta-thalassemia intermedia |
HbH: 3 alpha globin gene deletion
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What is this disease?
- intrauterine fetal death - Hb bart |
hydrop fetalis: 4 alpha globin gene deletion.
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What is the pathogenesis of HbH?
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3 alpha-globin gene deletion:
- high affinity for O2 -> hypoxia - prone to oxydation |
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An asian couple with alpha-thalassemia trait is considering having a child. What should you worry about?
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HbH in the child
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What is the most common genetic defect in PNH?
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CD59: potent inhibitor of C3 convertase
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What are some mutations involved in PNH?
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- CD59: potent inhibitor of C3 convertase
- CD55 - CD8 binding protein |
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Is PNH inheritable?
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No. The mutation is acquired.
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What are some complications of PNH?
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- episodic venous thrombosis: hepatic, portal, cerevral veins.
- risk of developing AML: because this is mutation in stem cells. |
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What type of hemolysis is PNH?
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intravascular
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Which model of immunohemolytic anemia do the following fit?
- penicillin - cephalosporin - quinidine |
hapten model (warm antibody)
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Which model of immunohemolytic anemia do the following fit?
- Aldomet (alpha-methyldopa) |
autoantibody model (warm antibody):
alpha-methyldopa most likely target Rh |
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Cold or warm immunolytic anemia?
- IgM - fix complement |
cold
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Cold or warm immunolytic anemia?
- IgG - does not fix complement |
warm
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Cold or warm immunolytic anemia?
- mycoplasma - infectious mono - CMV - influenza - HIV |
Cold
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Cold or warm immunolytic anemia?
- mycoplasma - infectious mono - CMV - influenza - HIV |
cold
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Cold or warm immunolytic anemia?
- mycoplasma - measles - mumps |
paroxysmal cold hemoglobinuria
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Cold or warm immunolytic anemia?
- extravascular hemolysis - mildly enlarged spleen |
warm
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Cold or warm immunolytic anemia?
- ears, fingers, toes mostly affected - vascular obstruction (pallor, cyanosis) |
cold
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Cold or warm immunolytic anemia?
- intermittent intravascular hemolysis after exposure to cold - increase indirect bilirubin |
paroxysmal cold hemoglobinuria
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How to diagnose immunohemolytic anemia?
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Coombs test
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What is Donath-Landsteiner antibody?
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antibody for P antigen developed after syphillus infection.
It may cause paroxysmal cold hemolgobinuria |
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What is this disease?
- blurr cells, helmet cells, schistocytes - fibrin deposits |
microangiopathic hemolytic anemia
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List some causes of microangiopathic hemolytic anemia.
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- cardiac valve prosthesis
- malignant HTN - SLE - TTP - HUS |
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What is this disease?
- macrocytic - normochromatic - low reticulocyte count |
megaloblastic anemia
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What is the function of R-binder? Where is it come from?
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R-binder
- bind to B12 in the stomache - from salivary gland |
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What is the function of IF? Where is it come from?
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IF:
- bind B12 in the duodenum - made by the parietal cels |
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Where is B12 absorbed in the intestines?
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Ilium: B12-IF bind to receptors on ileum.
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How does B12 get to the plasma?
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B12 associated with transcobamalineII in the ileum mucosal cell.
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What are the functions of B12?
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- cofactor for conversion of homocysteine to methionine
- aid isomerizaition of methylmalonyl coA to succinyl coA. |
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What is the underlying mechanism of B12 deficiency?
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Lack of B12 traps N5-methyl FH4 which is essential for DTMP synthesis which is needed for thymine synthesis.
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What are some causes of B12 deficiency?
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- long term inadequet diet
- gastrectomy - loss of pancreatic function - ileal resection - tape worm - pregnancy, hyperthyroidism, disseminated cancer, chronic infections. |
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What is this disease?
- high levels of homocysteine, methylmalonic acid - positive schilling test |
Vit B12 deficiency
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What is schilling test?
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Give PO radioactive B12 and measure urine levels to see if they are absorbed. If not, give IF to see if it corrects it. If it does, the patient is IF deficient.
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What will you see in the bone marrow of a B12 deficient patient?
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- marrow hyperplasia with decreased M/E ratio
- hypersegmented granulocytes - megaloblastic change |
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What are some complications of B12 deficient patients?
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- atrophic glossitis: shiny, glazed tongue.
- atriphy of fundic gland - gastric metaplasia, cancer - neurologic defect: subacute combined degeneration - atherosclerosis,thrombosis: elevated homocysteine and methylmalonic acid. |
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What is a specific diagnostic test for pernicious anemia?
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Serum test for anti-IF.
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What types of anti-IF are there for pernicious anemia and what are the predominance of each type?
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Type I(75%): anti-IF
Type II(50%): block B12-IF from binding to ileal receptors Type III(90%): target gastric pump |
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What is the underlying cause of pernicious anemia?
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antoreactive T cell -> antoantibodies against IF
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Why are the cells bigger in megaloblastic anemia?
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asynchronous nuclear/cytoplasm maturation.
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Where is folate absorbed?
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jejunum
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Where is B12 stored and for how long?
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B12 is stored in the liver for yrs.
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What food contains B12?
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meat only
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What food contains folate?
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- leafy vegetables: sensitive to heat
- meat |
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What drugs can cause megaloblastic anemia?
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cancer drugs
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Where is folate stored and for how long?
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Folate is stored in the liver for months.
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Which form of folate enters circulation?
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5-methyl FH4
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What are some causes of folate deficiency?
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1) decreased intake
- inadequate nutrition(alcoholics) - impaired intestinal absorption 2) increased requirement - pregnancy, infancy - hemolytic anemia - cancers 3) impaired use - methotrexate: ulcerative lesions in the GI |
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Which drug would cause megaloblastic anemia, specifically folate deficiency?
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methotrexate.
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How would alcolics develop foate deficiency?
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- traps folate in the liver
- excessive urinary loss - disordered folate synthesis |
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Folate deficiency affect which type of DNA synthesis? (purine or pyrimidine)
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purine
- DTMP synthesis |
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Which drugs block uptake of folate in the jejunum?
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- anticonvulsants
- BCP - INH |
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Which drugs act as folate antagonists?
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- methotrexate
- trimethoprim - pentamadine |
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What is the biochemical function of folate?
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- assist one carbon transfer
- purine synthesis - convert homosysteine to methionine (B12 needed) |
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What is this disease?
- microcytic, hypochromic - atrophic glossitis - esophageal webs |
Plummer-Vinson syndrome
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Where is iron absorbed?
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duodenum
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What substances inhence iron absorption?
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- ascorbic acid
- citrate acid - sugar |
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What substances inhibit iron absorption?
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- tea
- carbonates - oxalates - phosphate |
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Is hepcidin level high or low in iron deficiency anemia?
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Low
Hepcidin: inhibit iron uptake and release from macrophages |
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What is the function of hepcidin?
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Hepcidin: inhibit iron uptake and release from macrophages
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What is this disease?
- hypochromatic, microcytic - koilonychia, cheilosis - PICA |
iron deficiency anemia
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What is the most likely cause of iron defiency anemia in women before manopause?
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menses
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What is the most likely cause of iron defiency anemia in males and women before adolescence and after manopause?
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GI bleed until proven otherwise!
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What are some causes of iron deficient anemia in general?
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- dietary lack: infants, elderly, impoverished
- impaired absorption - increased requirement: pregnancy - chronic blood loss: hemorrhage, urinary and genital tract |
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What are these symmptoms indicative of?
- koilonychia - cheilosis - PICA - alopecia - atrophic glossitis |
iron deficiency anemia
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What is this?
- decrease Fe+, ferritin - increase transferrin |
iron deficiency anemia
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What is this disease?
- dyspnea on exertion - impaired catecholamine and T3 metabolism - hemosiderin in BM |
iron deficiency anemia
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What is the most common cause of anemia among hospitalized patients?
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anemia of chronic disease
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What is this disease?
- normocytic, normochromatic RBC - low Fe+,transferrin - high ferritin, high storage in bone marrow macrophages |
anemia of chronic disease
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Why is iron storage in macrophages high in anemia of chronic disase?
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chronic disease -> IL1,TNF,IFN -> stimulate hepcidin in liver -> no iron release from macrophages
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Why is EPO low in anemia of chronic disase?
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chronic disease -> IL1,TNF,IFN -> reduced EPO from kidney
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What are some chronic diseases that cause anemia?
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- chronic microbial infection
- chronic renal failure - chronic immune disorder rheumatoid arthritis enteritis - neoplasm Hodgkin's lymphoma lung cancer |
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What diseases may have atrophic glossitis?
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- B12 deficiency
- iron deficiency anemia - anemia of chronic diseases - plummer-vinson syndrome |
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What is this disease?
- no erythroid progenitor proliferation - shortened RBC survival - mild anemia |
Anemia of chronic disease
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What is this disease?
- no spleenomegaly - reticulocytopenia - slightly increased MCV - fibrous stroma in bone marrow - hypocellular bone marrow |
aplastic anemia
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What is Fanconi anemia?
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defect in multiprotein complex required for DNA repair -> T cell activation -> IFN,TNF -> bone marrow suppression
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What are some general causes of aplastic anemia?
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1) dose dependent myelotoxins
- benzene - chloramphenicol - alkylating agents - antimotabolites 2) idiosyncratic reaction to small dose drugs - streptomycin - chloramphenicol - phenylbutazone - chlorpromazine 3) whole body irradiation 4) viral infections: viral hepatitis |
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What are some myelotoxins that cause aplastic anemia at high doses?
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- benzene
- chloramphenicol - alkylating agents - antimotabolites |
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What are some drugs that cause aplastic anemia at small doses?
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- chloramphenicol
- phenylbutazone - streptomycin - chlorpromazine |
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What is a congenital pure red cell aplasia?
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Blacfan-Diamond syndrome
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What are some non-congenital cause of pure red cell aplasia?
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- immune mechanism
- 50% associated with thymoma - large granular lymphocytic leukemia - drugs |
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What is this disease?
- teat drop RBC - marrow infiltrated with lymphocytes |
myelophthisic anemia
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What hormone deficiency may cause anemia?
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- androgens
- thyroid hormone - adrenal steroids |
