Pathology

Question 1

Microcytic anemias

Answer 1

Iron deficiency, anemia of chronic disease, thalassemias, lead poisoning, sideroblastic anemia

Question 2

Normocytic anemias

Answer 2

Hemolytic or non-hemolytic (chronic disease, aplastic anemia)

Question 3

Macrocytic anemias

Answer 3

Megaloblastic (folate/B12 defciciency), non-megaloblastic (liver disease, alcoholism)

Question 4

Iron deficiency anemia

Answer 4

MICROCYTIC - chronic bleeding, malnutrition, or increased demand – decreased iron and ferritin, increased TIBC (transferrin) – fatigue, conjunctival pallor, spoon nails, difficulty swallowing

Question 5

Plummer Vinson syndrome

Answer 5

Plumbers DIE – Dysphagia, Iron defciency anemia, Esophageal webs

Question 6

a-thalassemia

Answer 6

MICROCYTIC - a-globin gene deletions (chromosome 16) – cis (Asians) or trans (African) – 4 deletions (Hb barts - y4 - hydrops fetalis), 3 deletions (HbH disease)

Question 7

B-thalassemia

Answer 7

MICROCYTIC - point mutations in Kozak sequence (chromosome 11) - Mediterranean – defective mRNA processing – minor (heterozygote) - Less B chain, asymptomatic, increased HbA2 – major (homozygote) - no B chain (have HbF), requires blood transfusions – crew cut on x-ray, skeletal deformities, chipmunk facies, extramedullary hematopoiesis (increased risk of parvovirus B12 aplastic crisis)

Question 8

Lead poisoning

Answer 8

MICROCYTIC – Inhibits ferrochelatase and ALA dehydratase – increase RBC protoporhyrin IX and d-ALA and decrease heme – basophilic stippling (retained aggregates of rRNA) – LEAD (Lead Lines on gingiva and bones, Encephalopathy, Abdominal colic and sideroblastic Anemia, Drops (wrist and foot) – Tx: Dimercaprol and EDTA (Succimer for kids)

Question 9

Sideroblastic anemia

Answer 9

Defect in heme synthesis — X-linked defect in d-ALA synthase – can be acquired, alcohol, lead, vitamin B6 deficiency, copper deficiency, isoniazid) – ringed sideroblasts (iron-laden PRUSSIAN BLUE STAIN mitochondria) – increased iron/ferritin, normal/decreased TIBC – Tx: Pyridoxine (B6)

Question 10

Hepcidin

Answer 10

Made in liver (decreases intestinal iron absorption and iron release from macrophages) – increased when iron is low

Question 11

Pure RBC Aplasia

Answer 11

Microcytic, hypochromic – CD8/IgG attack RBC precursors — d/t parvovirus B19, thymoma, leukemia

Question 12

Folate deficiency

Answer 12

MEGALOBLASTIC (hypersegmented PMNs) – impairs purine/pyrimidine synthesis – d/t malnutrition, malabsorption (jejunum), drugs (methotrexate, TMP, phenytoin), pregnancy – INCREASE HOMOCYSTEINE, NORMAL METHYLMALONIC ACID – No neurologic symptoms

Question 13

B12 (cobalamin) deficiency

Answer 13

MEGALOBLASTIC – Insufficient intake, malabsorption (ileum), pernicious anemia (no intrinsic factor), gastrectomy – INCREASED HOMOCYSTEINE AND METHYLMALONIC ACID – Neurologic symptoms (degeneration of spinocerebellar tract, lateral corticospinal tract, and dorsal column

Question 14

Orotic aciduria

Answer 14

Can’t convert orotic acid to UMP (defective UMP syntahse) – Failure to thrive, developmental delay, megaloblastic anemia refractory to folate/B12 – Orotic acid in urine – Tx: Uridine monophosphate

Question 15

Schilling Test

Answer 15

Give oral B12 – if normal urinary excretion then dietary deficiency — if decreased excretion then impaired absorption (can further test with intrinsic factor)

Question 16

Intravascular hemolysis

Answer 16

Decreased haptoglobin, increased LDH, schistocytes, increased reticulocytes — hemoglobin, hemosiderin, and urobilinogen in urine

Question 17

Extravascular hemolysis

Answer 17

Macrophages in spleen destroy RBCs – spherocytes, increased LDH, increased unconjugated bilirubin

Question 18

Anemia of chronic disease

Answer 18

Increased hepcidin, decreased iron, decreased TIBC, increased ferritin (storage) – Tx: EPO for chronic kidney disease

Question 19

Aplastic anemia

Answer 19

Myeloid cell issue due to radiation and drugs (chloramphenicol), viral agents (B19, EBV, HIV, HCV), Fanconi anemia, or idiopathic – pancytopenia (increased EPO due to compensation), hypocellular bone marrow with fat infiltrate – fatigue, pallor, mucosal bleeding, petechiae, infection – Tx: immunosuppression, bone marrow allograft, RBC/platelet transfusion, bone marrow stimulants

Question 20

Hereditary spherocytosis (E)

Answer 20

Defect in ankyrin, band 3, protein 4.2, spectrin (membrane proteins) — increased MHC, decreased haptoglobin, increased LDH, increased reticulocytes — splenomegaly, aplastic crisis, risk for gallstones – positive osmotic fragility test – Tx: splenectomy

Question 21

G6PD deficiency (I/E)

Answer 21

X-linked recessive — abnormal hexose monophosphate shunt (decreased glutathione so increased oxidative damage) — anemia following oxidative stress (sulfa drugs, dapsone, antimalarials, infections, fava beans) — Heinz bodies, bite cells

Question 22

Pyruvate kinase deficiency (E)

Answer 22

Hemolytic anemia in a newborn - autosomal recessive – decreased ATP

Question 23

HbC defect (E)

Answer 23

Glutamic acid to lysine mutation in B-globin

Question 24

Paroxysmal nocturnal hemoglobinuria (I)

Answer 24

Increased complement mediated RBC lysis – increased acute leukemias — pancytopenia, aplastic anemia, Coombs negative, venous thrombosis — CD55/59 negative — Tx: Eculizumab

Question 25

Sickle cell anemia (E)

Answer 25

Glutamic acid to valine substitution allows hydrophobic interaction between Hb in anoxic conditions --- low O2, high altitude, or acidosis leads to anemia and vaso-occlusive disease --- newborns are asymptomatic because HbF is protective -- heterozygotes have malaria resistance --- Crew cut on skull x-ray (marrow expansion) -- decreased haptoglobin --- Tx: hydroxyurea (increases HbF)

Question 26

Sickle cell complications

Answer 26

Aplastic crisis (parvovirus B19) -- autosplenectomy (Howell-Jolly bodies, increased risk of encapsulated organisms) -- splenic infarct (microvascular infarcts) -- Salmonella osteomyelitis -- painful crises (vaso-occlusive - acute chest syndrome, avascular necrosis, stroke) -- renal papillary necrosis

Question 27

Autoimmune hemolytic anemia

Answer 27

Warm agglutinin (IgG - chronic in SLE an dCLL or with drugs) -- Cold agglutinin (IgM - acute in CLL, Mycoplasma pneumonia, Mono) -- Coombs positive

Question 28

Coombs tests

Answer 28

Direct is checking for antibody on RBC -- indirect is checking for antibody in patient's serum

Question 29

Microangiopathic anemia

Answer 29

RBCs damaged when passing through obstructed vessel -- DIC, TTP/HUS, SLE, malignant hypertension --- schistocytes

Question 30

Macroangiopathic anemia

Answer 30

Prosthetic heart valves and aortic stenosis -- schistocytes

Question 31

Corticosteroid cell effects

Answer 31

Increase neutrophils, decrease lymphocytes and eosinophils

Question 32

Acute intermittent porphyria

Answer 32

Deficient porphobilinogen deaminase -- accumulation of porphobilinogen, d-ALA -- 5Ps (Painful abdomen, Port wine colored urine, Polyneuropathy, Psychological issues, Precipitated by drugs (cyp450 inducers, alcohol) -- Tx: Glucose and heme

Question 33

Porphyria cutanea tarda

Answer 33

Uroporphyrinogen decarboxylase deficiency -- accumulate uroporphyrin (tea colored urine) -- blistering cutaneous photosensitivity, red teeth, super hairy

Question 34

Heme pathway diseases

Answer 34

GAP UP (substrates - Glycine, Aminolevulinic acid, Porphobilinogen, Uroporphyrinogen, Protoporphyrin) = Some Doctors Prescribe Unlimited Ferrochelatase (enzymes - Synthase, Dehydratase, Porphobilinogen deaminase, Uroporphyrinogen decarboxyalse, Ferrochetalase) = SLAP Lead (diseases - Sideroblastic anemia, Lead poisoning, Acute intermittent porphyria, Porphyria cutanea tarda, Lead poisoning)

Question 35

Iron poisoning

Answer 35

Cell death due to peroxidation of membrane lipids -- Tx: chelation (deferoxamine, deferasirox)

Question 36

Hemophilias

Answer 36

Increased PTT, normal PT -- A (VIII - XR), B (IX - XR), C (XI - AR) --- macrohemorrhage, hemarthroses, easy bruising, bleeding after trauma --- Tx: desmopressin (releases factor 8 and vWF from endothelium) plus missing factor concentrate

Question 37

Vitamin K deficiency

Answer 37

Increased PT and PTT but normal bleedign time --- decreased factors 2, 7, 9, 10, protein C/S

Question 38

Platelet disorders

Answer 38

Increased bleeding time and microhemorrhage (mucosal bleeding, epistaxis, petechia)

Question 39

Bernard Soulier syndrome

Answer 39

Increased BT, large platelets -- decrased GpIb (defect in platelet to vWF adhesion)

Question 40

Glanzmann thrombasthenia

Answer 40

Increased BT -- decreased GpIIb/IIIa (defect in platelet to platelet aggregation) -- agglutination with ristocetin cofactor assay

Question 41

Immune thrombocytopenia

Answer 41

Decreased platelet count, increased BT -- anti-GpIIb/IIIa antibodies (viral illness) -- increased megakaryocytes -- Tx: steroids, IV Immunoglobulin

Question 42

Thrombotic thrombocytopenic purpura

Answer 42

Decreased platelet count, increased BT -- deficient ADAMST13 (decreased degradation of vWF multimers) -- increased large vWF multimers and increased platelet aggregation/thrombosis -- schistocytes, increased LDH --- neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia -- Tx: plasmapheresis, steorids

Question 43

von Willebrand disease

Answer 43

Increased BT and PTT -- lifelong history of mucosal bleeding -- autosomal dominant -- Ristocetin cofactor assay (decreased agglutination) -- Tx: desmopressin

Question 44

DIC

Answer 44

Decreased platelet count, increased BT/PT/PTT, increased D-dimers (fibrin split products), schistocytes, decreased fibrinogen, decreased factors V and VIII --- deficiency in clotting factors --- STOP Making New Thrombi (Sepsis, Trauma, Ob complections, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion, and snake bite)

Question 45

Antithrombin deficiency

Answer 45

Diminishes increase in PTT following heparin

Question 46

Factor V leiden

Answer 46

Resistant to degradation by activated protein C -- DVT, pregnancy loss, cerebral vein thrombosis

Question 47

Protein C or S deficiency

Answer 47

Increased risk of thrombotic skin necrosis with hemorrhage following warfarin administration -- Protein C Cancels Coagulation

Question 48

Prothrombin gene mutation

Answer 48

Increased plasma levels or prothrombin and venous clots

Question 49

Packed RBCs

Answer 49

Increase 1Hb/unit -- acute blood loss, severe anemia

Question 50

Platelets

Answer 50

Stop significant bleeding

Question 51

Fresh frozen plasma

Answer 51

Immediate warfarin reversal, cirrhosis, DIC

Question 52

Cryoprecipitate

Answer 52

Fibrinogen, factors 8, 13, vWF, fibronectin --- coagulation deficiencies involving fibrinogen and factor 8

Question 53

Leukemoid reaction

Answer 53

Increased LAP -- HUGE WBC count, left shift, lots of neutrophils

Question 54

Hodgkin lymphoma

Answer 54

Single group of nodes, contiguous spread, young adults and > 55, associated with EBV -- B signs (fever, night sweats, weight loss) --- Reed Sternberg cells (CD15/30 positive - owl eyes) -- nodular sclerosing form is most common

Question 55

Burkitt lymphoma

Answer 55

B cells -- young people -- t(8;14) c-myc and heavy chain Ig --- starry sky (macrophages) -- associated with EBV -- jaw lesion in Africa, pelvic/adomen in US

Question 56

Diffuse large B cell lymphoma

Answer 56

Older adults --- MC type in adults -- large lymph node or extranodal mass, Waldeyer ring, very agressive

Question 57

Follicular lymphoma

Answer 57

MC indolent form, can progress to DLBCL --- t(14;18) - BCL-2 (inhibits apoptosis) and Ig heavy chain -- painless, waxing and waning lymphadenopathy --- Tx: Rituximab

Question 58

Mantle cell lymphoma

Answer 58

B cells - Older males -- t(11;14) - cyclin D1 (G1 -> S) and heavy chain Ig --- CD5+

Question 59

Adult T cell lymphoma

Answer 59

Caused by HTLV -- cutaneous lesions, lytic bone lesions, hypercalcemia

Question 60

Mycosis fungoides/Sezary syndrome

Answer 60

Skin patches/plaques (cutaneous T cell lymphoma), atypical CD4+ T cells --- Sezary syndrome when it gets into circulation (T cell leukemia)

Question 61

Multiple myeloma

Answer 61

Plasma cell cancer that makes a lot of IgG or IgA --- people > 40-50 --- increased infections, punched out lytic bone lesions, M spike, Ig light chains in urine (Bence Jones protein), Rouleaux formation --- CRAB (hyperCalcemia, Renal involvement, Anemia, Back pain/Bone lytic lesions)

Question 62

Monoclonal gammopathy of undetermined significant

Answer 62

Monoclonal expansion of plasma cells, asymptomatic, no CRAB findings

Question 63

Waldenstrom macroglobulinemia

Answer 63

M spike = IgM --> hyperviscosity (blurred vision and Raynauds)

Question 64

Acute lymphoblastic leukemia

Answer 64

KIDS -- T cell can present as mediastinal mass (SVC like) --- DOWN SYNDROME! --- INCREASED LYMPHOBLASTS --- TdT+, CD 10+, Responds well to methotrexate -- t(12;21) has best prognosis

Question 65

Small lymphocytic lymphoma/chronic lymphoblastic leukemia

Answer 65

Adults > 60 (most common) -- CD20+, CD5+ -- SMUDGE CELLS -- Tx: Prednisone, Rituximab

Question 66

Hairy cell leukemia

Answer 66

Adults, hair like projections on cells --- dry tap on aspiration -- TRAP POSITIVE (tartrate resistant acid phosphatase) - old men with pancytopenia and splenomegaly --- Tx: Cladribine, pentostatin

Question 67

Acute myelogenous leukemia

Answer 67

Age 15-59 --- AUER RODS!!!!!!! -- Myeloperoxidase +, LOTS of circulating myeloblasts --- t (15;17) - M3 AML subtpye (Tx: ATRA causes differentiation of myelobalsts, DIC complication of treatment) --- Tx: Cytarabine

Question 68

Chronic myelogenous leukemia

Answer 68

Age 30-59 --- PHILADELPHIA CHROMOSOME t(9;22) BCR-ABL -- increased neutrophils, metamyeloblasts, BASOPHILIA -- very low LAP -- Tx: Imatinib

Question 69

Langerhans cell histiocytes

Answer 69

Lytic bone lesions and skin rash in child or recurrent otitis media with mass --- S-100 stain and Cd1a -- Birbeck granules (tennis rackets)

Question 70

Chronic myeloproliferative disorders

Answer 70

JAK2 (cytoplasmic tyrosine kinase) mutation --- activates JAK-STAT pathway

Question 71

Polycythemia vera

Answer 71

Increased hematocrit (increased RBCs/WBCs/platelets) -- decreased EPO due to negative feedback -- Intense itching after hot shower -- erythromelalgia (burning pain with red/blue color) due to blood clots in vessels of extremities --- Tx: phlebotomy/hydroxyurea

Question 72

Essential thrombocytosis

Answer 72

Overproduction of abnormal platelets -- enlarged megakaryocytes

Question 73

Myelofibrosis

Answer 73

Increased fibrosis in bone marrow -- TEARDROP RBCs -- dry tap -- massive splenomegaly --- Tx: Ruxolitinib

Question 74

Polycythemias

Answer 74

Relative (decreased plasma volume d/t deyhdration/burns) --- appropriate absolute (increasd RBC mass, decreased O2 saturation, increased EPO - lung/heart disease) --- inappropriate absolute (increased RBC mass, increased EPO - kidney/liver cancer due to ectopic EPO) --- vera (increased plasma volume, huge increased RBC mass, decreased EPO)