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Flashcards in Pathology - hem/onc Deck (72):
1

Acanthocyte

liver disease, abetalipoproteinemia

cholesterol dysregulation

2

Basophilic stippling

Lead poisoning

3

Degmacyte

G6PD deficiency

4

Elliptocyte

Hereditary elliptocytosis

5

Macro-ovalocyte

Megaloblastic anemia

6

Ringed sideroblast

excess iron in mitochondria

7

Schistocyte

DIC, TTP, HUS, HELLP

8

Sickle cell

Sickle cell

dehydration, deoxygenation, high altitude

9

Spherocyte

hereditary spherocytosis (incr. MCHC!)

10

Dacrocyte (teardrop cell)

Bone marrow infiltration (RBC squeezed out)

11

Target cell

HbC disease, Asplenia, Liver disease, Thalassemia

12

Heinz bodies

Oxidation of Hb-SH with subsequent phagocytic damage to RBC membrane (leads to bite cells)

G6PD deficiency

13

Howell-Jolly bodies

basophilic nuclear remnants found in RBCs

(normally removed by splenic macrophages)

sign of asplenia or functional asplenia (sickle-cell, polysplenia)

14

Microcytic, hypochromic anemias (5 total)

Iron deficiency
Alpha-thalassemia
Beta-thalessemia
Lead poisoning
Sideroblastic anemia

15

Lab tests in iron-deficiency anemia

decr. iron, incr. TIBC, decr. ferritin

look for conjunctival pallor and spool nails (koilonychia)

16

Gene deletions found in alpha-thalassemia

loss of alpha-globin gene

cis deletion = Asians
trans deletion = African

4 alleles deleted = incompatible with life
3 alleles deleted = very little alpha globin, HbH disease

17

Gene mutations found in beta-thalassemia

Point mutations in splice sites and promoter sequences

Minor: asymp. look for incr. HbA2

Major:
- symp after 6mos of age, req. blood transfusions
- marrow expansion --> bone deformities
- extramedullary hematopoiesis, incr. risk of parvob19 induced crisis

18

Lab/smear findings in lead poisoning

Lab: decr. heme synthesis, incr. protophorphyrin

Smear: rRNA aggregates --> basophilic stippling

19

Clinical findings of LEAD poisoning

Lead lines on x-ray: long bones and gingivae

Encephalopathy and RBC stippling

Abdominal colic and sideroblastic anemia

Drops - wrist and foot drop. Dimercaprol and EDTA

20

Causes of sideroblastic anemia

defect in heme synthesis

Genetic, acquired (myelodysplasia), reversible (alcohol, B6 deficiency, copper deficiency, isoniazid)

Use Prussian blue to stain iron-laden mitochondria

TX: B6/pyroxidine (provides co-factor)

21

Sideroblastic anemia labs

incr. iron, normal to decr. TIBC, incr. ferritin

22

4 causes of macrocytic anemia

Megaloblastic: folate deficiency, B12 deficiency, orotic aciduria

Nonmegaloblastic: unimpaired DAN synthesis (alcoholism, liver disease, hypothyroidism, reticulocytosis)

23

Mechanism of megaloblastic anemia

Impaired DNA synthesis --> maturation of nucleus of precursor cells in bone marrow is slower than the maturation of the cytoplasm

Leads to RBC macrocytosis and hypersegmented neutrophils

24

Folate vs. B12 deficiency

Folate = incr. homocysteine, normal MMA, no neuro sx

B12 = incr. homocysteine, incr. MMA, neuro sx "subacute combined degeneration"

25

Orotic aciduria vs. OTC deficiency

Orotic aciduria = defect in UMP synthase, no incr. NH4

OTC deficiency = incr. orotic acid and incr. NH4

26

Non-hemolytic normocytic normochromic anemia (2 total)

Anemia of chronic disease - incr. hepcidin, decr. iron release from macs (labs = decr. iron, decr. TIBC, incr. ferritin)

Aplastic anemia - failure or destruction of myeloid stem cells (radiation/drugs, viral agents, Fanconi anemia, idiopathic), fatty infiltration of marrow --> pancytopenia

27

Characteristics of intravascular hemolytic normocytic anemia

decr. haptoglobin, incr. LDH, schistocytes, incr. retics

think mechanical, PNG, MAHA

28

Characteristics of extravascular hemolytic normocytic anemia

Macs in spleen clear RBCs, so no Hgb in urine, incr. unconj bilirubin, jaundice

Ex. HS, PK deficiency, HbC defect, sickle cell anemia

29

HS protein defect

Ankyrin, spectrin --> small round RBCs with decr. surface area

Positive osmotic fragility test (blood mixed w/ 0.36% buffered saline)

30

Oxidative stress for G6PD patients

sulfa drugs, antimalarials, infections, fava beans

31

PNH mechanism

complement-mediated RBC lysis

impaired GPI anchor for DAF/CD55, which normally protects RBCs (loss of CD55, CD59)

Look for Coombs (-) anemia, pancytopenia, venous thrombosis (Budd-Chiari)

32

Sickle cell anemia mechanism

HbS point mutation (glutamic acid out, valine in on B-globin)

33

Complications from sickle cell anemia

aplastic crisis
autosplenectomy
splenic infarct (risk of SHiN infection!)
salmonella osteomyelitis
dactylitis/acute chest
renal papillary necrosis

34

Warm vs. cold autoimmune hemolytic anemia

(both are Coombs positive)

Warm (IgG) = chronic, SLE, CLL, drugs

Cold (IgM) = acute, seen in M. pneumoniae infections, Mono

35

Serum iron
TIBC/transferrin
Ferritin
% transferrin saturation

Iron-deficiency: decr***, incr, decr, double decr.

Chronic dz: decr. decr. incr***

36

Transferrin vs. ferritin

Transferrin: transports iron in blood
Ferritin: primary iron storage protein in the body

37

Three heme synthesis defects to know

Lead poisoning
Acute intermittent porphyria
Porphyria cutanea tarda

38

Enzymes affected in lead poisoning

Ferrochelatase and ALA dehydratase

accumulation of protoporphyrin, delta ALA

39

Enzymes affected in AIP

Porphobilinogen (PBG) deaminase

Porphobilinogen, delta ALA, coporphobilinogen (urine)

Can be precipitated by alcohol, smoking, rifampin, sulfonamides

Tx: glucose (to downregulate ALA synthase)

40

Enzymes in porphyria cutanea tarda

Uroporphyrinogen decarboxylase
Uroporphyrin (tea-colored urine)

41

Iron poisoning mechanism

Cell death due to peroxidation of membrane lipids

42

Factors tested by PT

Common pathway: 1, 2, 5
Extrinsic pathway: 7, 10

43

Factors tested by PTT

Common and intrinsic pathway

All factors except 7 and 10

44

Bleeding time

incr in BT = defect in platelet plug formation

45

Platelet disorders and specific defect

Bernard-Soulier: decr. GpIb (decr. plt to vWF adhesion)

Glanzmann: decr. GpIIb/IIIa (decr. plt to plt aggregation)

ITP: anti-GpIIb/IIIa antibodies

46

TTP mechanism

ADAMTS13 defect/absence --> decr. degradation of vWF multimers --> large multimers --> plt aggregation and thrombosis

Look for CNS sx, renal sx, fever, low plts, MAHA

47

Defects found in vWF disease

intrinsic pathway defect: loss of factor 8 (incr. PT)

defect in platelet plug formation (incr. bleeding time)

dx: ristocetin cofactor assay (primes platelets for vWF binding)
tx: desmopressin (incr vWF and factor 8 release)

48

Labs found in DIC

incr. fibrin split products, decr. fibrinogen, decr. factors 5 and 8

49

Mechanisms of antithrombin deficiency

inherited

acquired in renal failure/nephrotic syndrome (loss of factors in urine)

50

Protein C deficiency common syndrome

Skin and subcutaneous tissue necrosis after warfarin adminstration

51

FFP vs. cryoprecipitate

treat DIC, cirrhosis, warfarin reversal

vs.

coagulation factor deficiencies involving VII and fibrinogen

52

Leukemoid reaction vs. CML

Leukemoid = incr. WBC, incr. Leukocyte alkaline phosphatase

CML = incr. WBC, decr. LAP

53

Hodgkin lymphoma

location in body
cells
associations

Localized, single group of nodes, contiguous spread

Reed-Sternberg cells

assoc. with EBV

54

non-Hodgkin lymphoma

location in body
cells
associations

Multiple, peripheral nodes

B cells

assoc. HIV and autoimmune disease

55

Non-Hodgkin B cell lymphoma translocations

Burkitt
Follicular
Mantle cell

Burkitt - t8:14 (c-myc, transcription activator)
Follicular - t14:18 (BCL-2, oncogene that inhibits apoptosis, indolent!)
Mantle cell - t11:14 (cyclinD1, CD5 positive)

Ch. 14 = heavy chain Ig
Diffuse large cell - no translocation but most common non-Hodgkin lymphoma in adults

56

Non-Hodgkin T cell neoplasms

Adult T-cell lymphoma: caused by HTLV (assoc with IVDA)

Mycosis fungoides: cutaneous T-cell lymphoma

57

Multiple myeloma

products
diagnosis

IgG or IgA
M spike on serum protein electrophoresis
Ig light chains in urine (Bence-Jones)
Rouleaux formation (stacked RBCs)

CRAB: elevated Ca, Renal involvement, Anemia, Bone lytic lesion

Complications: incr. susceptibility to infection, amyloidosis (apple-green birefringence) in heart, tongue, kidney, CNS

58

TdT+, CD10+

ALL markers (can have pre-B cell leukemia precursor)

most responsive to therapy

young people

59

CD20+, CD5+ B cell neoplasm

SLL/CLL

old people

60

TRAP stain positive B cell neoplasm

Hairy cell leukemia

Marrow fibrosis (leads to dry tap on aspiration)

Tx: cladribine

61

Auer rods

Responds to Vitamin A

AML

Auer rods = stain for peroxidase, indicate myeloid differentiation

t(15;17) responds to Vitamin A (retinoic acid receptor)

62

t(9;22) translocation

CML, Philadelphia chromosome

63

Lytic bone lesions
Recurrent otitis media w/ mass involving mastoid bone

Langerhaans histiocytosis

S-100 marker, CD1a

64

JAK2 disorders (non-receptor tyrosine kinase assoc. w/ EPO receptor)

Polycythemia vera - itching after hot shower (incr. basophils)

Essential thrombocytosis - overproduction of abnormal platelets

Myelofibrosis - obliteration of bone marrow due to incr. fibroblast activity

65

Hemolytic-uremic syndrome (HUS)

Shiga toxin --> endothelial cell injury --> isolated activation of platelets --> RBC damage as they travel through narrrow lumens

66

Tumor suppressor genes

p53 (apoptosis inducer)
Rb (regulates G1 to S checkpoint, phosphorylated/mutated = inactive)
BRCA (DNA repair)
APC (tumor suppressor)
NF-1 (neurofibromatosis)

67

Protooncogenes

Ras (signal transduction)
Erb-B1 (tyrosine kinase)
Erb-B2/HER2 (tyrosine kinase)
N-myc (neuroblastoma)
C-myc (Burkitt, transcription activator)

68

Penetration of the basement membrane

1.) detachment of tumor cells (decr. E-cadherins)
2.) adhere to basement membrane (incr. laminin)
3.) invasion of BM (incr. metalloproteinases)

69

Cytokine mediator of cachexia

TNF-alpha

70

Factor V Leiden mechanism of pro-coagulation

increased coagulation (reduced susceptibility to cleavage) and decreased anticoagulation (decreased APC activity)

71

Oxidative stress is induced by...

Bactrim, dapsone, antimalarials, nitrofurantoin

fava beans

infection

72

Pure red cell aplasia (PRCA)

associated with thymoma, leukemia, parvovirus B19