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Pathology > Hem-Onc pathology > Flashcards

Hem-Onc pathology Flashcards

1
Q

Immune thrombocytopenic purpura (ITP)

A

Spleen produces anti-GpIIb/IIIa antibodies and consumes platelet/antibody complex.

Acute form arises after viral infection/immunization

Chronic form may arise secondary to SLE

Normal PT/PTT

Tx: corticosteroids, splenectomy

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2
Q

Microangiopathic hemolytic anemia

A

Platelets are consumed in production of platelet microthrombi within small vessels

Shearing of RBCs by microthrombi produce schistocytes

  1. Thrombotic thrombocytopenic purpura - decreased ADAMTS13 (vWF metalloprotease) leads to platelet adhesion to large vWF multimers; CNS abnormalities
  2. Hemolytic uremic syndrome - E. coli verotoxin damages endothelial cells resulting in platelet microthrombi; renal insufficiency

Tx: plasmapharesis, corticosteroids

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3
Q

Bernad-Soulier syndrome

A

Genetic GPIb deficiency impairs platelet adhesion to vWF

Mild thrombocytopenia and enlarged platelets

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4
Q

Glanzmann thrombasthenia

A

Genetic GPIIb/IIIa deficiency impairs platelet-to-platelet aggregation (via fibrinogen)

No platelet clumping seen on blood smear

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5
Q

Hemophilia A

A

X-linked recessive factor VIII deficiency (“A” = 8)

Elevated PTT; normal PT, PC, BT

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6
Q

Hemophilia B

A

Genetic factor IX deficiency

Elevated PTT; normal PT, PC, BT

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7
Q

von Willebrand disease

A

Genetic (usually AD) vWF deficiency

Increased BT, Increased PTT (vWF normally stabilized FVIII), normal PT

Abnormal ristocetin test (ristocetin causes vWF to bind platelet GPIb; decreased agglutination is diagnostic)

Tx: desmopressin (ADH analog, increases vWF release from Weibel-Palade bodies of endothelial cells)

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8
Q

Vitamin K deficiency

A

Vitamin K is normally activated by epoxide reductase in the liver; activated Vitamin K gamma carboxylates factors II, VII, IX, X, and proteins C (shorted t1/2) and S

Deficiency occurs in newborns (lack of GI colonizations), long-term antibiotic thearpy, malabsorption

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9
Q

Disseminated intravascular coagulation

A

Widespread activation of coagulation cascade, resulting in widespread microthrombi and consumption of platelets and clotting factors

Causes: gram negative sepsis, trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion

Decreased PC, Increased BT, Increased PT/PTT, Microangiopathic hemolytic anemia (schistocytes), Increased fibrin split products (D-dimers), Decreased fibrinogen

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10
Q

Fibrinolysis disorders

A

Normally, tissue plasminogen activator (tPA) converts plasminogen to plasmin

Plasmin cleaves fibrin and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation

alph2-antiplasmin inactivates plasmin

Plasmin overactivity results in increased BT, normal PC, increased PT/PTT, and increased fibrinogen split products (no D-dimers, unlike DIC)

Tx: aminocaproic acid (blocks plasminogen activation)

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11
Q

Causes of endothelial cell damage

A
  • Atherosclerosis
  • Vasculitis
  • Hyperhomocystenemia:
    • Vitamin B12 or folate deficiency
    • Cystathionine beta synthase deficiency (vessel thrombosis, mental retardation, lens dislocation, long slender fingers)
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12
Q

Protein C or S deficiency

A

Autosomal dominant hypercoagulable state

Proteins C and S normally inactivate factors V and VIII

Increased risk for warfarin skin necrosis

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13
Q

Factor V Leiden

A

Hypercoagulable state due to a mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S

Most common inherited cause of hypercoagulable state

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14
Q

ATIII deficiency

A

Hypercoagulable state resulting in decreased protective effects of heparin-like molecules produced by the endothelium

In ATIII deficiency, PTT does not rise with standard heparin dosing

May be acquired through nephrotic syndrome

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15
Q

Causes of iron deficiency

A
  • Breast-feeding
  • Poor diet
  • Peptic ulcer disease
  • Menorrhagia/pregnancy
  • Colon polyps/carcinoma
  • Hookworm (Ancylostoma duodenale, Necator americanus)
  • Gastrectomy (acid maintains Fe+2 state, aids in absorption)
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16
Q

Stages of iron deficiency

A
  1. Depletion of storage iron (decreased ferritin, increased TIBC)
  2. Depletion of serum iron (decreased % saturation)
  3. Normocytic anemia (BM makes fewer but normal-sized RBCs)
  4. Microcytic, hypochromic anemia

Concomitant normocytic and microcytic anemias increase RDW

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17
Q

Plummer-Vinson syndrome

A

Iron deficiency anemia with esophageal web and atrophic glossitis

Presents as anemia, dysphagia, and beefy-red tongue

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18
Q

Hepcidin

A

Acute phase reactant that limits iron transfer from macrophages to erythroid precursors and suppresses EPO production

Important in pathophysiology of anemia of chronic disease

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19
Q

Sideroblastic anemia

A

Microcytic anemia caused by defective protoporphyrin synthesis leading to an accumulation of iron in mitochondria

Congenital defect: X-linked defect in aminolevulinic acid synthetase (ALAS) gene (ALAS normally converts succinyl CoA to ALA using vit B6 as a cofactor)

Acquired defects: alcoholism (mitrchondrial poison), lead poisoning (inhibits ALAD and ferrochelatase), vit B6 deficiency (required cofactor for ALAS; side effect of isoniazid tx)

Ringed sideroblasts and lab findings of iron-overloaded state (increased ferritin, decreased TIBC, increased serum iron, increased % saturation)

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20
Q

Lead poisoning

A

Inhibits ferrochelatase (mitochondrial enzyme that combines protoporphyrin with Fe+2 to produce heme)

Inhibits ALA dehydratase (cytosomal enzyme that converts ALA to prophobilinogen)

Protoporphyrin and ALA accumulate in the blood

Presents as sideroblastic anemia with basophilic stippling (inhibits rRNA degradation), “lead lines” on gingivae (Burton lines) and metaphyses of long bones, encephalopathy, abdominal colic, and wrist/foot drop.

Tx: Dimercaprol, EDTA, Succimer (chelating agents)

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21
Q

Acute intermittent porphyria

A

Defective porphobilinogen deaminase (cytosomal enzyme that converts porphobilinogen to hydroxymethylbilane)

Porphobilinogen, ALA, and coporphobilinogen accumulate in urine

Presents as “5 P’s”: Painful abdomen, Port wine-colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs, alcohol, and starvation

Tx: glucose and heme (inhibit ALA synthase)

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22
Q

Porphyria cutanea tarda

A

Deficient uroporphyrinogen decarboxylase (cytosomal enzyme that converts uroporphyrinogen III to coproporphyrinogen III)

Uroporphyrin accumulates (tea-colored urine)

Presents as blistering cutaneous photosensitivity.

Most common porphyria

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23
Q

Alpha-thalassemia

A

Deletion of alpha globin gene

cis deletion prevalent in Asian populations (increased risk of severe thalassemia in offspring)

trans deletion prevalent in African populations

3 allele deletion - beta-chains form tetramers (HbH)

4 allele deletion - gamma-chains form tetramers (Hb barts); lethal in utero (hydrops fetalis)

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24
Q

Beta-thalassemia

A

Decreased beta-globin synthesis due to point mutations in splice sites and promoter sequences

Prevalant in Mediterranean populations

Beta-thalassemia minor - beta chain is underproduced; increased HbA2

Beta-thalassemia major -beta chain is absent; increased HbF; requires blood transfusion; marrow expansion and extramedullary hematopoiesis

HbS/Beta-thalassemia heterozygote - mild to moderate sickle cell disease

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25
Q

Folate deficiency

A

Causes: poor diet (alcoholics), increased demand (hemolytic anemia, pregnancy), folate antagonists (methotrexate)

Folate is absorbed in the jejunum

Symptoms: megaloblastic anemia with hypersegmented neutrophils, glossitis, increased serum homocysteine (increased risk for thrombosis), normal methylmalonic acid

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26
Q

Vitamin B12 deficiency

A
  • Pernicious anemia (autoimmune destruction of parietal cells)
  • Pancreatic insufficiency (lack of pancreatic proteases result in failure to detach vit B12 from R-binder)
  • Damage to terminal ileum (e.g. Crohn disease or Diphyllobothrium latum [fish tapeworm])
  • Vegan diet
  • Proton pump inhibitors

Symptoms: megaloblastic anemia with hypersegmented neutrophils, glossitis, increased serum homocysteine (increased risk for thrombosis), increased methylmalonic acid (impairs spinal cord myelinization, results in subacute combined degeneration of the spinal cord)

Subacute combined degeneration: poor proprioception and vibratory sensation, and spastic paresis

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27
Q

Orotic aciduria

A

Megaloblastic anemia caused by autosomal recessive defect in uridine monophosphate (UMP) synthass, resulting in an inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway)

Tx: UMP, to bypass mutated enzyme

28
Q

Causes of nonmegaloblastic macrocytic anemias

A
  • Liver disease
  • Alcoholism
  • Reticulocytosis
  • Drugs (5-FU, zidovudine, hydroxyurea)
29
Q

Characteristics of extravascular hemolysis

A

RBC destruction by reticuloendothelial system

  • Anemia with splenomegaly
  • Jaundice due to unconjugated bilirubin
  • Increased risk for bilirubin gallstones
  • Marrows hyperplasia with corrected retic count >3%
30
Q

Characteristics of intravascular hemolysis

A
  • Hemoglobinemia
  • Hemoglobinuria
  • Hemosiderinuria
  • Decreased serum haptoglobin
31
Q

Hereditary spherocytosis

A

Inherited defect of RBC cytoskeleton-membrane tethering proteins (ankyrin, spectrin, band 3)

Increased MCHC and Increased RDW.

Premature removal of RBCs by spleen –> splenomegaly and risk of aplastic crisis (parvovirus B19)

Dx: osmotic fragility test, eosin-5-maleimide binding test

Tx: splenectomy

32
Q

Sickle cell anemia

A

Autosomal recessive point mutation (valine replaces glutamate in beta chain)

Increased risk of sickling with hypoxemia, dehydration, and acidosis

Complications: extramedullary hematopoiesis, increased risk of aplastic crisis (parvovirus B19), dactylitis (common presenting sign in infants), autosplenectomy (infection with encapsulated organism most common cause of death in children), salmonella osteomyelitis, acute chest syndrome (msot common cause of death in adults), pain crisis, renal papillary necrosis, renal medullary infarcts

Dx: metabisulfite screen, Hb electrophoresis

Tx: hydroxyurea (increases HbF)

33
Q

Hemoglobin C

A

Autosomal recessive point mutation (lysine replaces glutamate in beta chain) “lyCine”

Formation of characteristic HbC crystals

34
Q

Causes of aplastic anemia

A
  • Radiation
  • Drugs (benzene, choramphenicol, alkylating agents, antimetabolites)
  • Viruses (parvovirus B19, EBV, HIV, HCV)
  • Fanconi anemia (DNA repair defect)
  • Idiopathic (may follow acute hepatitis)
35
Q

Paroxysmal nocturnal hemoglobinuria

A

Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI), which normally secures decay accelerating factor (DAF, CD55) to cell membrane; loss of DAF renders cells susceptible to complement destruction

Sleep –> mild respiratory acidosis –> activation of complement –> lysis of RBCs, WBCs, and platelets

Complications: thrombosis (hepatic, portal, cerebral veins), iron deficiency anemia (due to hemoglobinuria), acute myeloid leukemia (AML)

Tx: eculizumab (inhibit complement system)

36
Q

G6PD deficiency

A

X-linked recessive disorder resulting in reduced half-life of G6PD, which renders cells susceptible to oxidative stress

African variant is less severe than the Mediterranean variant

Causes of oxidative stress: infection, drugs (primaquine, sulfa drugs, dapsone), fava beans

Heinz bodies (denatured Hgb) and bite cells

Presents with hemoglobinuria and back pain after exposure to oxidative stress

37
Q

Autoimmune hemolytic anemia

A

Extravascular hemolysis resulting in spherocytes

  • IgG (warm agglutinin) - SLE, CLL, penicillin (IgG attaches to pencillin/membrane complex), alpha-methyldopa (induces production of IgA autoantibodies)
  • IgM (cold agglutinin) - fixes complement to membrane and residual C3b serves as opsonin for splenic macrophages; Myoplasma pneumonia, infectious mono

Coombs positive

38
Q

Direct Coombs test

A

Anti-Ig antibody (Coombs reagent) is added to patient’s blood. RBCs agglutinate if RBCs are coated with Ig

39
Q

Indirect Coombs test

A

Normal RBCs are added to patient’s serum. If serum has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibodies (Coombs reagent) is added.

40
Q

Effects of corticosteroids on WBC count

A
  • Neutrophilia (impairs neutrophil adhesion, leading to release of marginated pool of neutrophils into bloodstream)
  • Leukopenia (induce apoptosis)
  • Eosinophilia (sequester in lymph nodes)
41
Q

Infectious mononucleosis

A

Commonly caused by EBV, less commonly caused by CMV

EBV infects oropharynx (pharyngitis), liver (hepatitis), and B cells

CD8+ T cell response caused generalized LAD (T cell hyperplasia in LN paracortex), splenomegaly (T cell hyperplasia in periarterial lymphatic sheat), and atypical lymphocytosis

Monospot test detects heterophile IgM antibodies (think CMV if monospot is negative)

Complications: splenic rupture, rash if exposed to ampicillin, B-cell lymphoma

42
Q

Acute lymphoblastic leukemia

A

TdT+ (nuclear marker of pre-T and pre-B cells)

Children. Associated with Down syndrome after the age of 5

  • B-ALL - lymphoblasts express CD10, CD19, CD20; excellent response to chemo but requires prophylaxis to scrotum and CSF
    • t(12;21) - good prognosis
    • t(9/22) - poor prognosis; more common in adults
  • T-ALL - lymphoblasts express CD2-CD8; present in teenagers as a thymic mass
43
Q

Acute promyelocytic leukemia

A

Subtype of AML; MPO+ (crystals seen as Auer rods)

t(15;17) translocation of retinoic acid receptor blocks maturation of promyelocytes

Increased risk for DIC

Tx: all-trans-retinoic acid (ATRA) binds altered receptor and forces blasts to mature

44
Q

Acute monocytic leukemia

A

Subtype of AML; MPO-

Blasts characteristically infiltrate gums

45
Q

Acute megakaryoblastic leukemia

A

Subtype of AML; MPO-

Associated with Down syndrome before the age of 5 (vs. ALL which is associated with Down syndrome after the age of 5)

46
Q

Myelodysplastic syndrome

A

Defect in cell maturation of all non-lymphoid lineages. Increased blast production but <20% blasts in bone marrow

Caused by de novo mutations or environmental exposure (radiation, benzene, chemo).

Risk of transformation to AML

47
Q

Chronic lymphocytic leukemia

A

Naive B cells that co-express CD5 (normally just on T cells) and CD20

Increased lymphocytes and smudge cells on blood smear

Involvement of lymph nodes –> small lymphocytic lymphoma

Complications: hypogammaglobulinemia (infection), autoimmune hemolytic anemia, transformation to diffuse large B-cell lymphoma (Richter transformation)

48
Q

Hairy cell leukemia

A

Mature TRAP+ B cells characterized by hairy cytoplasmic processes

Splenomegaly (accumulation of hairy cells in red pulp) and “dry tap” on bone marrow aspiration (due to fibrosis)

Absent LAD

Tx: 2-CDA (cladribine) - adenosine deaminase inhibitor that accumulates adenosine in neoplastic B cells to toxic levels

49
Q

Adult T-cell leukemia/lymphoma

A

Mature CD4+ T cells associated with HTLV-1

Japan, West Africa, and the Caribbean

Rash, generalized LAD with hepatosplenomegaly, and lytic (“punched-out”) bone lesions with hypercalcemia

Don’t confuse with multiple myeloma

50
Q

Mycosis fungoides

A

Mature CD4 T cells that form aggregates of neoplastic cells in the epidermis called Pautrier microabscesses

Skin rash, plaques, nodules

Sezary syndrome occurs if cells spread into the blood (characteristic cerebriform nuclei on blood smear)

51
Q

Chronic myeloid leukemia

A

Proliferation of mature myeloid cells, especially granulocytes (basophils are characteristic)

t(9;22) Philadelphia chromosome generates a BCR-ABL fusion protein with increased tyrosine kinase activity; blocked by imatinib

Complications: splenomegaly, transformation to AML (2/3) or ALL (1/3) since mutation is in pluripotent stem cells

Differentiated from leukemoid rxn by negative LAP stain, increased basophils, and t(9;22)

52
Q

Polycythemia vera

A

Proliferaiton of mature myeloid cells, especially RBCs

JAK2 kinase mutation (hematopoietic growth factor)

Symptoms: blurry vision, headache, increased risk of venous thrombosis (Budd Chiari syndrome), flushed face, itching after bathing (histamine release from mast cells)

Tx: phlebotomy, hydroxyurea

53
Q

Essential thrombocythemia

A

Proliferation of mature myeloid cells, especially platelets

JAK2 kinase mutation

Increased risk of bleeding and/or thrombosis

No significant risk for hyperuricemia

54
Q

Myelofibrosis

A

Proliferation of mature myeloid cells, especially megakaryocytes (produce PDGF causing marrow fibrosis)

JAK2 kinase mutation

Extrameduallary hematopoiesis (splenomegaly)

Leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, immature granulocytes)

Increased risk of infection, thrombosis, and bleeding

55
Q

Follicular lymphoma

A

Proliferation of small CD20+ B cells that form follicle-like nodules

Presents in late adulthood with painless “waxing and waning” LAD; normal LN architecture is disrupted with no tingible body macrophages in germinal centers; monoclonality

t(14;18) - translocation of heavy-chain Ig (14) and bcl-2 (inhibits apoptosis)

Tx: rituximab (anti-CD20 antibody)

Complications: progression to diffuse large B-cell lymphoma

56
Q

Mantle cell lymphoma

A

Progression of small CD20+ B cells that expand mantle zone

Presents in older males with painless LAD

t(11:14) - translocation of heavy-chain Ig (14) and cyclin D1 (promotes G1/S transition)

57
Q

Marginal zone lymphoma

A

Proliferation of small CD20+ B cells that expand marginal zone

Associated with chronic inflammatory states (Hashimoto thryoiditis, Sjogren syndrome, H pylori gastritis)

MALToma is marginal zone lymphoma in mucosal sites

58
Q

Burkitt lymphoma

A

Proliferation of intermediate-sized CD20+ B cells, classically as an extranodal mass in a child or young adult; associated with EBV

African form usually involves the jaw; sporadic forms usually involves the abdomen

t(8;14) - translocation of heavy-chain Ig (14) and c-myc (promotes cell growth)

High mitotic index and “starry-sky” appearance

59
Q

Diffuse large B cell lymphoma

A

Proliferation of large CD20+ B cells that grow diffusely in sheets; most common form of NHL in adults; high grade and clinically aggressive

May arise sporadically or from follicular lymphomas - t(14;18)

60
Q

Hodgkin lymphoma

A

Proliferation of Reed-Sternberg cells (CD15/CD30+ large B cells with owl-eyed nuclei); rarely extranodal

RS cells secrete cytokines that recruit lymphocytes, plasma cells, macrophages, and eosinophils, produce “B” symptoms, and may lead to fibrosis

  • Nodular sclerosis - most common subtype, affects young female adults, LN divided by sclerosis, RS cells in lake-like spaces (“lacunar cells”)
  • Lymphocyte-rich - best prognosis
  • Lymphocyte-depleted - worst prognosis; HIV+
  • Mixed cellularity - abundant eosinophils
61
Q

Multiple myeloma

A

Malignant proliferation of plasma cells in bone marrow; most common primary malignancy of bone; associated with high serum IL-6 (stimulates plasma growth and Ig production)

  • Lytic (“punched-out”) skeletal lesions with hypercalcemia (due to activation of RANK receptor on osteoclasts)
  • M spike on SPEP, due to monoclonal IgG or IgA
  • Increased risk of infection
  • Rouleuax formation of RBCs on blood smear
  • Free light chains enter blood (primary AL amyloidosis), urine (Bence Jones protein), and kidneys (myeloma kidney)
62
Q

Monoclonal gammopathy of undetermined significance (MGUS)

A

M spike on SPEP without other features of MM (lytic bone lesions, hypercalcemia, AL amyloid, Bence Jones proteinuria)

63
Q

Waldenstrom macroglobulinemia

A

B-cell lymphoma with monoclonal IgM production

No lytic bone lesions

Large IgM pentamer causes serum hyperviscosity (visual and neurologic deficits, defective platelet aggregation)

Tx: plasmapheresis

64
Q

Langerhans cell histiocytosis

A

Langerhans cells are monocyte-derived CD1a+ and S100+ specialized dendritic cells, characterized by Birbeck (tennis racket) granules, found predominantly in skin

  • Letterer-Siwe disease - malignant proliferation of Langerhans cells in infants <2 yo; skin rash and cystic skeletal defects; rapidly fatal
  • Hand-Schuller-Christian disease - malignant proliferation of Langerhans cells in infants >3yo; scalp rash, lytic skull lesion, diabetes insipidus, exopthalmos
  • Eosinophilic granuloma - benign proliferation of Langerhans cells in bone; characteristic pathologic fracture in an adolescent; no skin involvement
65
Q

Carcinomas that spread hematogenously

A
  • Renal cell carcinoma (invades renal vein)
  • Hepatocellular carcinoma (invades hepatic vein)
  • Follicular carcinoma of the thyroid
  • Choriocarcinoma

Hematogenous spread is also characteristics of sarcomas

Pathology (17 decks)

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