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70 Cards in this Set
- Front
- Back
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Beta-thalassemia minor (heterozygote)
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-POINT MUTATION
-Beta-chain is underproduced, asymptomatic, protection against malaria, Diagnose by increased HbA2 (a2d2) on electrophoresis (> 3.5%), target cells, increased HbF (a2g2) |
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Beta-thalassemia major
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-POINT MUTATION
-Beta chain is absent- the aggregated alpha chains in RBCs cause death in the BM (ineffective erythropoeisis), leading to increased iron absorption from the gut to compensate and secondary hemochromatosis- need to give defuroxamine or else die of cardiac disease. The RBCs that do make it out of the BM are destroyed in the spleen, leading to anemia, increased EPO, BM expansion and skeletal abnormalities (chipmunk facies) -Extramedullary hematopoeisis: HSM, LAD. -Increased HbF (a2g2) |
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Alpha-thalassemia
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-DELETION of genes (1-2 no anemia; 3 is HbH disease (B4), 4 is incompatible with life (g4 = Hb Barts and causes hydrops fetalis and spontaneous abortion- increased risk of choriocarcinoma for mom)
-Seen in asians and african populations |
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Lead poisoning
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-Inhibits ferrochelatase and ALA dehydratase (decreased heme synthesis)
-Inhibits rRNA degradation- basophilic stippling due to aggregation of ribosomes -Increased protoporphyrin -Lead lines on gingivae and epiphyses of long bones, encephalopathy, abdominal colic and sideroblastic anemia, foot and wrist drops, gout -Treat with EDTA (adults) or succimer (kids) |
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Sideroblastic anemia
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-X linked defect of ALA synthase (RLS for heme synthesis and requires B6)
-May be due to alcohol or lead -Increased Fe, normal TIBC, and increased ferritin -Ringed sideroblasts (with iron-laden mitochondria) -Treat with B6 |
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Megaloblastic anemia (folate)
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-Due to malnutrition (alcoholics), malabsorption (celiac disease), impaired metabolism (MTX, TMP, phenytoin), increased requirement (pregnancy, hemolytic anemia)
-Hypersegmented neutrophils, decreased folate/increased homocysteine/normal MMA -Macroovalocytes |
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Megaloblastic anemia (cobalamine)
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-Glossitis/dec B12/increased homocysteine/increased MMA/increased LDH
-Due to insufficient intake (vegans), malabsorption (Crohn's), pernicious anemia, pancreatitis, Diphyllobothrium latum -Neurological symptoms due to abnormal myelin: subacute combined degeneration (corticospinal- UMN, posterior coloumns), dementia, peripheral neuropathy with sensorimotor dysfunction -Macroovalocytes |
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Nonmegaloblastic macrocytic anemias
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-Liver disease
-Alcoholism (even in the absence of folate or B12 deficiency) -Reticulocytosis -Metabolic disorder (orotic aciduria due to CPS II deficiency)- Purine or pyrimidine synthesis deficiencies -Drugs; 5-FU, AZT, hydroxyurea |
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Anemia of Chronic Disease
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-Due to chronic inflammation (microbial infections such as osteomyelitis, bacterial endocarditis, lung absesses; immune disorders, neoplasms)- hepcidin that is produced causes iron to stay in macrophages, resulting in decreased Fe, DECREASED TIBC, INCREASED FERRITIN
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Aplastic anemia
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-Pancytopenia (anemia, neutropenia, thrombocytopenia)
-Hypocellular BM with FATTY infiltration (dry tap), no splenomegaly, reticulocytes are reduced -Caused by radiation/drugs (chlorampehnicol, benzene, alkylating agents, antimetabolites, NSAIDs, PTU, methimazole), viral agents (parvovirus B19, EBV, HIV, HCV) esp in sickle cell, Fanconi's anemia (DNA repair defect), idiopathic -Patients present with fatigue, pallor, malaise, purpura, mucosal bleeding, petechiae, infection -Treat with G-CSF or GM-CSF |
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Kidney disease
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-Decreased EPO, decreased hematopoiesis (DM MCC)
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Hereditary spherocytosis
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-Extravascular hemolysis (in MPs)
-Defect in ankyrin, spectrin, band 4.1 (structural proteins) -Small round RBCs with no central pallor (increased MCHC and RDW) -Triad of anemia, SPM, jaundice. Also see aplastic crisis (parvovirus B19) and pigmented gallstones -Positive osmotic fragility test (hemolysis at 0.65%) -Treat with splenectomy so that the RBCs are not destroyed (see Howell-Jolly bodies afterwards) |
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G6PD deficiency
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-Intravascular hemolysis
-X-linked defect in G6PD (decreased NADPH and glutathione) leads to increased susceptibility to oxidative stress (INH, Sulfa drugs, Primaquine ASA Ibuprofin Nitrofurantoin- hemolysis IS PAIN; also dapsone, fava beans, napthalene. -Heinz bodies (denatured oxidized Hb precipitates) and bite cells -Back pain, hemoglobinuria a few days later |
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Pyruvate kinase deficiency
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-Extravascular hemolysis
-AR; defect in PK causes decreased ATP and rigid RBCs (RBCs can only use metabolize pyruvate to lactate for energy) -Hemolytic anemia in the newborn |
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Sickle cell anemia (HbS)
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-Extravascular hemolysis
-Single aa replacement in beta-chain (glutamic acid to valine at position 6- more positive charge). -Deoxygenated HbS polymerizes and sickles (low O2, dehydration, or acidity precipitates this) -Anemia, vasoocclusive disease -Skull crew cut because of marrow expansion and increased erythropoeisis. |
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Sickle cell anemia (HbC)
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-Glutamic acid to lysine (more positive charge than HbS) at position 6
-Patients with HbSC have milder disease than HbSS |
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Complications in homozygotes (sickle cell disease)
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-Aplastic crisis (B19 infection)
-Autosplenectomy leads to increased risk of encapsulated organisms (S. pneumo, H. flu, N. meningitidis) and Howell Jolly bodies -Salmonella osteomyelitis -Renal papillary necrosis (low O2 in papillae) and microhematuria (medullary infarcts) -Splenic sequesteration crisis: infarction of the spleen (wedge shaped) |
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Paroxysmal nocturla hemoglobinuria
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-Intravascular hemolysis
-Impaired synthesis of DAF (CD 55 and CD 59) which normally inhibits complement on RBCs, or impaired synthesis of GPI anchor -Increased urine hemosiderin, episodic hemoglobinuria, decreased haptoglobin -HAM's test- acidified serum test -Budd Chiari, acute leukemia |
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Warm agglutinin (IgG): Autoimmune hemolytic anemia (Type II hypersensitivity)
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-SLE, CLL, drugs (alpha-methyldopa, penicillin, quinidine)
-Coombs positive |
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Cold agglutinin (IgM): Autoimmune hemolytic anemia (Type II hypersensitivity)
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-Mycoplasma, CLL, infectious mononucleosis (EBV), INH, quinidine
-Acute anemia triggered by cold -Coombs positive |
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Erythroblastosis fetalis: Autoimmune hemolytic anemia (Type II hypersensitivity)
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-Rh (+) newborns born to Rh (-) mothers
-Coombs positive |
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Microangiopathic anemia
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-Intravascular hemolysis
-RBCs damaged when passing through obstructed or narrow vessel lumen -DIC, TTP-HUS, SLE, malignant hypertension, HELLP syndrome -See shistocytes |
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Macroangiopathic anemia
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-Prosthetic heart valves and aortic stenosis cause hemolytic anemia secondary to mechanical destruction.
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Infections
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-Increased destruction of RBCs by malaria and babesia
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Acute intermittent porphyria
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-Defect in porphobilinogen deaminase (uroporphyrinogen I-synthase) leading to a buildup of porphobilinogen, d-ALA, and uroporphyrin (see in urine)
-Present with painful abdomen (often mistaken for acute abdomen so have scars from unnecessary surgeries) -Red wine-colored urine upon standing -Polyneuropathy -Psychological disturbances -EtOH, barbiturates can precipitate -Treat with glucose and heme (inhibit ALA synthase) |
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Porphyria cutanea tarda
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-Defect in uroporphyrinogen decarboxylase leading to a build up of uroporphyrin in the urine (tea-colored)
-Bilstering on sun exposed skin, hypertrichosis, precipitated by alcohol, HCV. Increased LFTs |
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Intravascular hemolysis
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-Decreased haptoglobin (binds and clears free hemoglobin), increased LDH, hemoglobinuria, hemoglobinemia
-PNH, mechanical destruction, autoimmune hemolytic anemias |
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Extravascular hemolysis
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-Increased LDH, increased UCB (jaundice), pigment stones (bilirubin-rich), splenomegaly
-Hereditary spherocytosis, G6PD deficiency, sickle cell, pyruvate kinase defect |
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Burkitt's lymphoma
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-t(8;14) c-myc gene (TF) moves next to Ig heavy chain
-Starry sky appearance with interspersed MP, associated with EBV -Jaw lesion in Africa, pelvis or abdomen in sporadic, HIV associated -Ki-67; Mature B cell (CD 10+) |
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Diffuse large B-cell lymphoma
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-Mature B cell (CD 10+)
-Most common adult NHL, 20% are T-cell origin, aggressive |
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Mantle cell lymphoma
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-Mature B cell, CD 5+
-Older males, poor prognosis -t (11;14) |
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Follicular lymphoma
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-Mature B cell, CD 10+
-t (14;18) bcl2 (anti-apoptotic) expression -Slowly enlarging painless LAD, see aggregated of packed follicles, abdominal discomfort, remissions and recurrence |
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Multiple myeloma associations
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-Hypercalcemia (stimulates osteoclasts and inhibits osteoblasts), renal insufficiency (nephrolithiasis), Anemia, Bone lytic lesions/Back pain. Bence Jones proteins can form casts in tubules (large eosinophilic) and see them in the urine (Ig light chains- need UPEP or SPEP to see), rouleaux formation, M spike (IgG/IgA), punched out lytic bone lesions on Xray
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Acute lymphoblastic leukemia/lymphoma (ALL)
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>50% lymphoblasts in BM, >20% blasts circulating
-Bone marrow replaced by lots of lymphoblasts. CHILDREN; Presents with mediastinal mass in adolescent males and compression of the trachea and esophagus (dysphagia, dyspnea; can be T-cell origin here). Bone pain is common -TdT +, CALLA +, PAS + -Can spread to CNS and testes; t(12;21) better prognosis |
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Small lymphocytic lymphoma (SLL)/Chronic lymphocytic leukemia (CLL)
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-Smudge cells, often asymptomatic, warm agglutinins. OLDER ADULTS.
-SLL and CLL are the same except CLL has increased peripheral lymphocytosis |
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Hairy cell leukemia
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-Elderly
-Mature B-cell tumor; cells have hairlike projections. -TRAP stain!!!!! |
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Acute myelogenous leukemia (AML)
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>50% myelobasts in BM, >20% blasts circulating
-Adults; Greatly increased number of circulating myeloblasts on peripheral smear. Auer rods (peroxidase positive) -15;17 responds to ATRA (M3 subtype), which induces differentiation of myeloblasts. -CD13/33 (+), PAS (-). This is how you differentiate it from ALL -Associated with Downs, radiation, alkylating agents |
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Chronic myelogenous leukemia (CML)
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-Philadelphia chromosome (9;22) bcr-abl (tyrosine kinase)
-Age 30-60 -increased neutrophils, metamyelocytes, basophils, SPLENOMEGALY, LAD -Can progress to AML/ALL (blast crisis) -Very low leukocyte ALP (vs leukemoid reaction) -LOW leukocyte alk phos (distinguishes it from leukemoid reaction) -Treat with imatinib |
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What is myeloperoxidase?
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Contained in neutrophils and involved in the respiratory burst; responsible fro the green color of pus (heme containing pigmented molecule)
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What enzymes are produced by eosinophils?
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Major basic protein- Helminthic infections (damages EC and epithelial cells)
Histaminase and arylsulfatase- Limit reaction following mast cell degranulation |
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What do basophils do?
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Mediate allergic reactions; granules contain heparin, histamine, LTD-4, and other vasoactive amines. Found in BLOOD (as opposed to mast cells which are in tissue)
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What is in mast cells?
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Histamine (vasodilates, increases gastric H+), heparin, eosinophil chemotactic factors, tryptase
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What is inside endothelial cells involved in coagulation?
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vWF, thromboplastin (tissue factor), tPA, PGI2
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What disorders are associated with target cells?
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HbC disease, Asplenia, Liver disease, Thalassemia (beta)
HALT said the target |
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What disorders are associated wtih basophilic stippling?
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Thalassemias, Anemia of chronic disease, Iron deficiency, Lead poisoning
Bste the ox TAIL |
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What causes macrocytic anemias?
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Impaired DNA synthesis- maturation of the nucleus is delayed relative to maturation of the cytoplasm. Ineffective erythropoiesis leads to pancytopenia.
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What lab values are seen in Fe-deficiency anemia?
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Fe- dec
TIBC- inc ferritin- dec % transferrin saturation- markedly dec |
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What lab values are seen in ACD?
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Fe- dec
TIBC- dec Ferritin- increased (acute phase) % transferrin saturation- Normal or slight increase |
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What lab values are seen in hemochromatosis?
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Fe- increased (primary problem)
TIBC- Decreased Ferritin- Increased % transferrin saturation- markedly increased |
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What lab values are seen in pregnancy/OCP?
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Fe- no change
TIBC- Increased (primary problem because estrogen increases transferrin) Ferritin- no change % transferring saturation- Decreased |
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What lab values are seen in lead poisoning?
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Fe- Increased
TIBC- Decreased Ferritin- No change % transferrin saturation- Increased |
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What is seen in ITP?
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-Decreased platelet survival because of antibodies against GpIIb/IIIa
-Increased megakaryocytes on labs -Decreased PC, increased BT |
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What is seen in TTP?
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-Decreased platelet survival (decreased PC, increased BT)
-Deficiency of ADAMTS 13 (vWF metalloprotease), leading to decreased degradation of vWF multimers, increased platelet aggregation, and thrombosis. -Labs: schistocytes, increased LDH |
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What is the pentad seen in TTP?
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Neurologic symptoms, kidney failure, fever, thrombocytopenia, and microangiopathic hemolytic anemia
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Which platelet disorder does NOT decrease platelet count?
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Bernard-Soulier
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What defects are seen in vWD?
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-Intrinsic pathway (vWF carries/protects VIII) so increased PTT
-Platelet plug formation -Treat with DDAVP (releases vWF stored in endothelial cells) -(+) risocetin test |
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What are patients with Protein C or S deficiency at an increased risk for?
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Thrombotic skin necrosis with hemorrhage following administration of warfarin.
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What cell surface markers are on Reed-Sternberg cells?
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CD15, CD30 (B-cell origin)
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How do you differentiate between multiple myeloma and Waldenstrom's macroglobinemia?
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Multiple myeloma- M spike is IgG/IgA
Waldenstrom's- M spike is IgM |
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MGUS
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Monoclonal plasma cell expansion without the symptoms of multiple myeloma
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Langerhans cell histiocytosis
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Dendritic cell proliferation- express S-100 and CD1a. Birbeck granules (tennis rackets on EM)
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What is seen in myelofibrosis?
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-Fibrotic obliteration of the bone marrow, leading to tear drop cells
-Leads to decrease in RBCs, and variable effects on WBCs and platelets |
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What is involved in hematopoietic growth factor signaling?
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JAK2
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What is polycythemia vera?
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Abnormal clone of HSCs are increasingly sensitive to growth factors so that RBCs, WBCs, and platelets increase. By definition there is decreased EPO. The plasma volume increases. This can be due to RCC, Wilms' tumor, cysts, HCC, hydronephrosis.
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What is appropriate absolute polycythemia?
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-An increase in hematocrit due to increased RBC mass because of lung disease, congenital heart disease, high altitude (hypoxia)
-Increased RBC mass, decreased O2 saturation, increased EPO, no change in plasma volume |
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What causes relative polycythemia?
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There is no increase in RBC mass; the hematocrit is increased because of decreased plasma volume (dehydration, excessive diuresis)
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What is inappropriate absolute polycythemia?
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Increase in hematocrit due to increased RBC mass from ectopic EPO production. The O2 saturation and plasma volume are not changed.
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What is a prothrombin gene mutation?
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Mutation in the 3' untranslated region associated with venous clots.
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What would happen to someone with a protein C or S deficiency who was given warfarin?
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Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
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Nodular sclerosis Hodgkins Lymphoma
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Excellent prognosis (high lymphocyte/RS); Most common; collagen banding; lacunar cells; women > men; primarily young adults
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