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98 Cards in this Set
- Front
- Back
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Erythrocytes
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RBC
chloride-bicarbonate antiporter responsible for the "physiology chloride shift" that allows RBCs to pump Bicarb out in exchange for Cl to transport CO2 Types: A/B/AB/O - IgM antibodies that do not cross placenta Rh= IgG antibodies that can cause erythroblastosis fetalis in Rh+ fetuses in Rh- mothers that have been presensitized to Rh |
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beta-thalassemia
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microcytic, hypochromic anemia
major: severe anemia, marrow expansion, chipmunk facies -> homozygote of beta-globin point mutations tx with blood transfusion that can lead to secondary hemochromatosis minor: beta chain underproduced, usually asymptomatic, increased HbA2 on electrophoresis both have increasesd HbF HbS/beta-thalassemia heterozygote- mild/moderate sickle disease depending on amount of beta produced |
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Lead poisoning anemia
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microcytic, hypochromic anemia
Lead lines on gingivae/epiphyses of long bones Encephalopathy and erythrocyte basophilic stippling Abdominal colica and sideroblastic anemia Wrist/foot Drop (LEAD) inhinbits ferrochelatase and ALA-dehdratase -> prevents heme synth treat with Dimercaprol and EDTA |
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Sideroblastic anemia
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microcytic, hypochromic anemia
ringed sideroblasts (Fe-laden mitochondria) increased Fe, normal TIBC, increased ferritin X-linked defect in delta-aminoleuvulnic acid synthase gene -> defective heme synth tx: pyridoxine (B6) |
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Folate deficiency anemia
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macrocytic, megaloblastic anemia
hypersegmented neutrophils, glossitis, decreased folate *normal methylmalonic acid and no neuro symptoms* etiologies, malnutrition, malabsorption, drugs, increased requirements |
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B12 (cobalamin) deficiency anemia
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megaloblastic, macrocytic anemia
glossitis Neurologic symptoms: subacture combined degeneration due to build up of FA in myelin 1. peripheray neuropathy, lost vibration/proprioception, spasticity, dementia hypersegmented neutrophils, decreased B12, increased homocysteine and *methylmaonic acid* etiologies: insufficient intake, malabsorption, pernicious anema, Diphyllobothrium latum (fish tapeworm) |
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nonmegaloblastic macrocytic anemias
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DNA synthesis is unimpaired but full maturation of RBC is impaired
causes liver disease, alcoholism, reticulocytosis (rebound growth), metabolic disorder, congenital deficiencies of purine and pyrimidine synth, drugs |
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Intravascular hemolysis
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decreased haptoglobin, increased LDH, Hb in urine
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extravascular hemolysis
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increased LDH and unconjugated bilirubin
macrophages in spleen clear of RBC |
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anemia of chronic disease
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nonhemolytic, normocytic anemia
decreased iron, TIBC (can't release Fe and all remains bound), increased ferritin inflammation causes an increased in hepcidin -> impairs release of iron from macrophages |
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aplastic anemia
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fatigue, malaise, pallor, purpua, mucosal bleeding,petechiae, infections
pancytopenia, normal cell morphology but hypocellular bone marrow with fatty infiltrate causes: failure or destruction of myeloid precursors 1. radiation/drugs 2. viral agents (parvovirus B19, EBV, HIV, HCV) 3. fanconi's anemia (DNA repair defect) 4. idiopathic often following acute hepatitis tx: cause, immunosuppression, bone marrow transplant, transfusion, G/GM-CSF |
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Kidney disease and anemia
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decreased erythropoietin leads to decreased hematopoiesis
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Hereditary spherocytosis
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hemolytic normocytic anemia
splenomegaly. aplastic crisis (B19 infection) positive osmotic fragility test defect in cytoskeletal proteins interacting with RBC membrane (ankyrin, band 3, protein 4.2, spectrin) small round RBC with no central pallor increased MCHC, RDW leads to premature removal by spleen tx with splenectomy -> Howell-Jolly bodies |
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G6PD deficiency
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back pain, hemoglobinuria often after oxidant stress (fava beens, sulfa, infections, antimalarials)
X-linked hemolytic normocytic anemia defect in HMP shunt that decreases glutathione -> RBC can't handle oxidative stress RBCs with Heinz bodies and bite cells |
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Pyruvate kinase deficiency
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hemolytic normocytic anemia in newborn
AR- deficiency leading to decreased ATP -> rigid RBCs |
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Paroxysmal nocturnal hemoglobinuria
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hemolytic normocytic anemia that worsens at night, increased urine hemosiderin, can cause thrombosis
increased complement-RBC lysis impaired synthesis of GPI anchor/decay accelerating factor on RBC that normally prevents complement from attacking own cells CD59 negative |
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Sickle cell anemia
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skull findings
Complications: 1. aplastic crisis due to parvovirus B19 2. autosplenetomy increased encapsulated organisms 3. splenic sequestration crisis 4. Salmonella osteomyelitis 5. vaso-occlusive criss 6. renal papillary necrosis, microhematuria HbS point mutation in beta-chain = valine for glutamine at position 6 low 02 causes HbS polymeriation tx: hydroxyurea leads to increased HbF |
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Autoimmune hemolytic anemia
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warm agglutinin (IgG) - chronic anemia in SLE, CLL, with certain drugs (Warm weather is GGGreat)
cold agglutinin (IgM) acute anemia triggered by cold: LL, Mycoplasma pneuminia, mono (Cold ice cream MMM) Coombs' test positive |
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Coombs' test
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direct- anti-Ig antibody added to patient's RBCS agglutinate if RBC coated with Ig
indirect- normal RBCs added to patient's serum - agglutinate if serum has anti-RBC surface Ig |
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Erythroblastosis fetalis
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seen in Rh+ newborns born to presensitized Rh- mothers
bilirubin can build up ion basal ganglia - kernicterus newborns are direct coombs' positive, mother are indirect positive |
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Microangiopathic anemia
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RBCs damaged when passing through obstructed or narrowed vessel lumina
schistocytes on smear DIC, TTP-HUS, SLE, malignant hypertension |
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Macroangiopathic anemia
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schistocytes
most oten due to prosthetic heart valves |
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infections and hemolytic anemia
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malaria - schizont
Babesia - maltese cross (four-point cross) |
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Iron deficiency lab values
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decreased serum iron, increased transferrin/TIBC, decreased ferritin, greatly decreased transferring saturation
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Anemia of chronic disease lab values
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decreased serum iron, decreased transferrin/TIBC, increased ferritin
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Hemochromatosis lab values
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increased serum iron, decreased transferrin/TIBC, increased ferritin, increased transferrin saturation
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Lead poisoning porphyria
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microcytic anemia, GI, kidney disease
kids -> mental deterioration adults -> headache, memory loss, demyelination lead inibits ferrochelatase and ALA deydratase leading to accumulation of protoporphyrin |
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acute intermittent porphyria
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painful abdomen, red wine urine, polyneuropathy, psychological disturbances
precipitated by many drugs porphobilinogen deaminase deficiency leads to build up of porphobilinogen, delta-aminolevulinic acid (ALA), uroporphyrin (urine) tx: glucose and heme which inhibit ALA synthetase (heme negative feedback important regulation) |
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porphyria cutanea tarda
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blistering cutaneous photosensitivity- most common porphyria
uroporphyrinogen decarboxylase deficiency leads to accumulation of uroporphyrin (tea-colored urine) |
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Platelets
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dense granules (ADP, calcium) and alpha-granules (vWF and fibrinogen)
approximatel 1/3 stored in spleen so splenectomy cna increase platelet pool <50,000 will have inappropriate bleeding, <20,000 will bleed spontaneously |
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Hemophilia A or B
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macrohemorrhage, hemarthroses, easy bruising, unexplained bleeding (circumcision)
X-linked increased PTT but normal PT A- factor VIII (milder) B- factor IX |
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Vitamin K deficiency
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general coagulation defect
decreased synthesis of factors II, VII, IX, X, protein C, protein S increased PT and PTT PET and PITT (PT = extrinsic, PTT = intrinsic) |
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PT
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tests function of I, II, V, VII, and X (extrinsic)
will not show changes in platelet disorders |
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PTT
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tests function of VII and XIII (intrinsic)
will not show change in platelet disorders |
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Bernard-Soulier disease
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microhemorrhage, mucous membrane bleeding, epistaxis, petechiase, purpura, increased bleeding time
defect in platelet plug formation decreased Gp1B expressed on platelets -> defect in platelet-vWF adhesion decreased PC |
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Glanzmann's thrombasthenia
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microhemorrhage, mucous membrane bleeding, epistaxis, petechiase, purpura, increased bleeding time
defect in platelet plug formation decreased in GpIIb/IIIa causing a defect in platelet-platelet aggregation normal PC, |
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Idiopathic thrombocytopenic purpura
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microhemorrhage, mucous membrane bleeding, epistaxis, petechiase, purpura, increased bleeding time
decreased platelet survival due to anti-GPIIb/IIIa antibodies that target platelets for destruction in spleen causes: kids postviral, adults secondary to other disorder decreased PC, increased megakaryocytes |
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Thrombotic thrombocytopenic purpura
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pentad of neurological and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
deficiency in ADAMTS 13- (vWF metalloprotease) -> degradation of vWF multimers -> increased platelet aggregation and thrombosis schistocytes, increased LDH, decreased PC |
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von Willebrand's disease
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vWF carries and protects VIII loss leads to loss of VIII which results in an increase in PTT
defect in platelet-vWF adhesion -> plaletlet plugs don't form AD, mild but most common bleeding disorder treat with DDAVP (desmospressin) that stimulates release of vWF from endothelium |
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disseminated intravascular coagulation
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widespread activation of clotting leads to deficiency in clotting factors, which promotes bleeding
causes: Sepsis (gram negative), Trauma, Obstetric complications, acute Pancreatitis, Malignacny, Nephrotic syndrome, Transfusion (STOP Making New Thrombi) labs show schistocytes, increased D dimers, decreased fibrinogen, decreased factors V and VIII |
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Hemolytic uremic syndrome
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form of TTP that occrus in kids after bloody gastroenteritis caused by hemolytic E. coli O157:H7
no fever or neurologic symptoms |
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acute lymphoblastic leukemia/lymphoma
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generic leukemia symptoms: anemia, infections, hemorrhage in kids under 15yrs
bone marrow replaced by lymphoblasts- terminal deoxynucleotidyl transferase positive (marker for pre-T/B cells) CALLA(+) (CD10) - common acute LL antigen + is good prognosis generally responsive especially if CALLA+ or with t(12;21) |
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small lymphocytic lymphoma/chronic lymphocytic leukemia
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often asymptomatic: smudge cells in peripheral blood smear, warm antibody autoimmune hemolytic anemia (IgG)
age >60 yrs SLL same as CLL except CLL has increased lymphocytosis |
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Hairy cell leukemia
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generic leukemia symptoms in adults, mature B-cell tumor in elderly
cells have filamentous, hairlike projections stains TRAP (+) IT'S A TRAP! |
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Acute myelogenous leukemia
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DIC is a common presentation, leukemia symptoms
60 yrs, Auer rods, increased myeloblasts t(15;17) subtype has good prognosis -> M3 AML subtype responds to all-trans retinoic acid (VitA) -> differentiation of myeloblasts |
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Chronic myelogenous leukemia
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leukemia symptoms: age 30-60 years, splenomegaly, may accelerate and transform to AML or ALL
defined by Philadelphia chromosome t(9;22) bcr-abl responds to imatinib- inhibitor of bcr-abl lvery low leukocyte alkphos due to immmature granulocytes (differs from leukemoid reaction) |
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t(9;22)
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philadelphia chromosome CML- bcr-abl
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t(8;14)
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Burkitt's lymphoma (c-myc activation ->transcription activation/proliferation)
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t(14;18)
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follicular lymphomas (bcl-2 activation inhibits apoptosis)
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t(15;17)
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M3 type of AML - cellular differentiation can be treated with VitA
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t(11;22)
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Ewing''s sarcoma (EWS/Fl1 fusion protein)
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t(12;14)
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mantle cell lymphoma - tumor cell growth - cyclin D overexpression
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Langerhans cell histiocytosis
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immature dendritic cell proliferation that don';t stimulate T lymphocytes, express S-100 and CD1a, birbeck granules (tennis rackets)
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Polycythemia vera
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increased RBC, WBC, platelets
JAK2 mutations abnormal clone of hematopoietic stem cells are increasingly sensitive to growth factors *Low EPO* need to rule out RCC, WIlm's tumor, cyst, HCC< hydronephrosis |
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essential thrombocytosis
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increased platelets Jak2 positive in 30-50%
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myelofibrosis
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fibrotic obliteration of bone marrow, teardrop cell
decreased RBC, JAK2 mutation 30-50% |
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JAK2
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hematopoietic growth factor signaling
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Myeloid metaplasia pathway
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excessive cell proliferation such as polycythemia vera -> bone marrow "burnout" -> myelofibrosis -> liver/spleen begin to produce RBC -> myeloid metaplasia
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Heparin
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cofactor for activation of antithrombin, decreased thrombin, Xa used for emergent anticoagulation
safe in pregnancy (does not cross placenta), follow PTT SE: heparin induced thrombocytopenia: heparin binds factor IV, antibodies bind and platelets activated resulting in hypercoagulable state, protamine sulfate can neutralize overdose low-molecular-weight heparins - more specific for Xa, better bioavailability, longer t1/2 |
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Lepirudin, bivalirudin
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hirudin derivatives, directly inhibit thrombin
used as an alternative to heparin for patients with HIT |
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Warfarin
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interferes with normal synthesis and gamma-carboxylation of VitK-dependent clotting factors II, VII, IX, X, and protein C,S.
Cytochrome p-450 pathway changes PT (extrinsic pathway) not for pregnant women- teratogenic tx overdose: VitK, severe give fresh frozen plasma to return clotting factors |
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Thromblytics
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tPA most important, also streptokinase, urokinase, APSAC
directly or indirectly aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots increases PT/PTT but no change in platelets treat toxicity with aminocaproic acid an inhibitor of fibrinolysis |
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Aspirin
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acetylates and irreversibly inhibits cyclooxygenase to prevent synth of thromboxane A2
no effect on PT/PTT SE: bleeding, gastric ulcers, hyperventilation: respiratory alkalosis which can progress to elevated anion gap metabolic acidosis, Reye's syndrome, tinnitus (sign of severe toxicity) decreased secretion with decreased pH tx with bicarb |
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Clopidogrel, ticlopidine
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inhibit platelet aggregation by irreversibly blocking ADP receptors, inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
acute coronary syndrome, stenting ticlopidine can cause neutropenia |
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Abciximab
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monoclonal antibody that binds to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
uses: MI, cath se; bleeding, thrombocytopenia |
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Methotrexate
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antimetabolite; folic acid analog that inhibits dihydrofolate reductase, decreased dTMP -> decreased DNA/protein synth
used: cancers *abortion/ectopic pregnancy* RA se: myelosuppresion that can be rescued with leucovorin, macrovesicular fatty change in liver, mucositis, teratogenic |
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5-fluorouracil (5-FU)
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pyrimidine analog bioactived to 5F-dUMP which covalently complexes folic acid -> inhibits thymidylate synthase -> dTMP -> decreased DNA?protein synth
SE: myelosuppression rescued with thymidine not leucovorin, photosensitivity |
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6-mercaptopurine
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purine (thiol) analog decreases de novo purine synth
activated by HGPRTase (hypoxanthine-guanine phosphotibosyltransferase) SE: bome marrow, GI, liver metabolized by xanthine axidase- interaction with allopurinol |
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6-thioguanine
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purine (thiol) analog decreases de novo purine synth
activated by HGPRTase (hypoxanthine-guanine phosphotibosyltransferase) not metabolized by xanthine oxidase so can be given with allopurinol |
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cytarabine (ara-C)
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pyrimidine analog inhibits DNA pol
leukopenia, thromboxytopenia, megaloblastic anemia |
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Dactinomycin
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antitumore antibiotic
forms free radicals that intercalate in DNA *used for childhood tumors* (Kids ACT out) |
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doxorubicin, daunorubicin
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generate free radicals, noncovalently intercalate DNA - breaks -> decreased replication
*cardiotoxicity* dilated cardiomyopathy dexrazoxane (Fe chelator) can prevent toxicity |
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Bleomycin
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free radical formation that break DNA strands
*causes pulmonary fibrosis* skin changes, minimal myelosuppression |
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Etoposide (VP-16), teniposide
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inhibits topoisomerase II -> DNA degradation
small cell carcinoma |
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Cyclophosphamide, ifosfamide
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covalently crosslink (interstrand) DNA at guanine N-7, activated by liver
hemorrhagic cystitis, partially prevented witih mesna that binds toxic metabolite |
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nitrosoureas [-ustine]. (carmustin, lomustine, semustine, streptozocin)
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*require bioactivation, cross BBB*
*CNS toxicity* dizziness, ataxia |
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busulfan
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alkylates DNA
can cause pulmonary fibrosis |
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Vincristine, vinblastine
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alkaloids that bind to tubulin in *M-phase* and block polymerization of microtubules
vincristine - neurotoxicity (areflexia, neuritis) paralytic ileus (CNS - Crist) vinBLASTine BLASTs, Bone- marrow suppression |
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paclitaxel, other taxols
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hyperstabilize polymerized microtubules in M-phase
myelosuppression and hypersensitivity |
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cisplatin, carboplatin
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cross-link DNA
nephrotoxicity and acoustic nerve damage, - prevent nephrotoxicity with amidostine and chloride diuresis |
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hydroxyurea
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inhibits ribonucleotide reductase -> DNA synth (S phase)
sickle cell increases HbF |
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prednisone
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most common glucocorticoid in cancer chem
Cushing-like symptoms monitor for decrease K, Ca, ad increased Na |
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tamoxigen, raloxifene
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SERMs
tamoxifen may increase endometrial cancer vie partial estrogen agonism raloxifene no increase because it is an antagonist |
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trastuzumab (herceptin)
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monoclonal antibody against HER-2 (erb-B2)
cardiotoxicity |
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imatinib
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bcr-abl tyrosine kinase inhibitor
CML, GI stromal tumors SE: fluid retention |
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rituximab
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monoclonal antibody against CD20 which is found on most B-cell neoplasms
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HTLV-1 associated cancer
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adult T-cell leukemia/lymphoma
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HBV, HCV associated cancer
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hepatocellular carcinoma
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EBV cancer
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burkitt's lymphoma, hodgkin's lymohoma, nasopharyngeal carcinoma
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HPV cancer
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cervical carcinoma (16/18), penile/anal carcinoma
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HHV-8 cancer
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Kaposi's sarcoma, body cavity fluid B-cell lymphoma
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HIV cancer
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primary CNS lymphoma, primarily occurs when CD4 cells <50
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H. pylori cancer
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gastric adenocarcinoma and lymphoma
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Schistosoma haematobium cancer
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squamous cell carcinoma of transtitional epithelium esp. bladder
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Factor V Leiden disease
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production of mutant factor V that cannot be degraded by protein C - most common cause of inherited hypercoagulability
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Prothrombin gene mutation
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mutation in the 3' untranslated region of prothrombin
associated with venous clots |
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antithrombin deficiency
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inherited deficiency, less response to heparin
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protein C or S deficiency
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inability to inactivate factors V and VIII, increased risk of thrombotic skin necrosis with hemorrhage following warfarin
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