Pathology - hem/onc Flashcards
Acanthocyte
liver disease, abetalipoproteinemia
cholesterol dysregulation
Basophilic stippling
Lead poisoning
Degmacyte
G6PD deficiency
Elliptocyte
Hereditary elliptocytosis
Macro-ovalocyte
Megaloblastic anemia
Ringed sideroblast
excess iron in mitochondria
Schistocyte
DIC, TTP, HUS, HELLP
Sickle cell
Sickle cell
dehydration, deoxygenation, high altitude
Spherocyte
hereditary spherocytosis (incr. MCHC!)
Dacrocyte (teardrop cell)
Bone marrow infiltration (RBC squeezed out)
Target cell
HbC disease, Asplenia, Liver disease, Thalassemia
Heinz bodies
Oxidation of Hb-SH with subsequent phagocytic damage to RBC membrane (leads to bite cells)
G6PD deficiency
Howell-Jolly bodies
basophilic nuclear remnants found in RBCs
(normally removed by splenic macrophages)
sign of asplenia or functional asplenia (sickle-cell, polysplenia)
Microcytic, hypochromic anemias (5 total)
Iron deficiency Alpha-thalassemia Beta-thalessemia Lead poisoning Sideroblastic anemia
Lab tests in iron-deficiency anemia
decr. iron, incr. TIBC, decr. ferritin
look for conjunctival pallor and spool nails (koilonychia)
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
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
Lab/smear findings in lead poisoning
Lab: decr. heme synthesis, incr. protophorphyrin
Smear: rRNA aggregates –> basophilic stippling
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
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)
Sideroblastic anemia labs
incr. iron, normal to decr. TIBC, incr. ferritin
4 causes of macrocytic anemia
Megaloblastic: folate deficiency, B12 deficiency, orotic aciduria
Nonmegaloblastic: unimpaired DAN synthesis (alcoholism, liver disease, hypothyroidism, reticulocytosis)
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
Folate vs. B12 deficiency
Folate = incr. homocysteine, normal MMA, no neuro sx
B12 = incr. homocysteine, incr. MMA, neuro sx “subacute combined degeneration”
Orotic aciduria vs. OTC deficiency
Orotic aciduria = defect in UMP synthase, no incr. NH4
OTC deficiency = incr. orotic acid and incr. NH4
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
Characteristics of intravascular hemolytic normocytic anemia
decr. haptoglobin, incr. LDH, schistocytes, incr. retics
think mechanical, PNG, MAHA
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
HS protein defect
Ankyrin, spectrin –> small round RBCs with decr. surface area
Positive osmotic fragility test (blood mixed w/ 0.36% buffered saline)
Oxidative stress for G6PD patients
sulfa drugs, antimalarials, infections, fava beans
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)
Sickle cell anemia mechanism
HbS point mutation (glutamic acid out, valine in on B-globin)
Complications from sickle cell anemia
aplastic crisis autosplenectomy splenic infarct (risk of SHiN infection!) salmonella osteomyelitis dactylitis/acute chest renal papillary necrosis
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
Serum iron
TIBC/transferrin
Ferritin
% transferrin saturation
Iron-deficiency: decr***, incr, decr, double decr.
Chronic dz: decr. decr. incr***
Transferrin vs. ferritin
Transferrin: transports iron in blood
Ferritin: primary iron storage protein in the body
Three heme synthesis defects to know
Lead poisoning
Acute intermittent porphyria
Porphyria cutanea tarda
Enzymes affected in lead poisoning
Ferrochelatase and ALA dehydratase
accumulation of protoporphyrin, delta ALA
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)
Enzymes in porphyria cutanea tarda
Uroporphyrinogen decarboxylase
Uroporphyrin (tea-colored urine)
Iron poisoning mechanism
Cell death due to peroxidation of membrane lipids
Factors tested by PT
Common pathway: 1, 2, 5
Extrinsic pathway: 7, 10
Factors tested by PTT
Common and intrinsic pathway
All factors except 7 and 10
Bleeding time
incr in BT = defect in platelet plug formation
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
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
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)
Labs found in DIC
incr. fibrin split products, decr. fibrinogen, decr. factors 5 and 8
Mechanisms of antithrombin deficiency
inherited
acquired in renal failure/nephrotic syndrome (loss of factors in urine)
Protein C deficiency common syndrome
Skin and subcutaneous tissue necrosis after warfarin adminstration
FFP vs. cryoprecipitate
treat DIC, cirrhosis, warfarin reversal
vs.
coagulation factor deficiencies involving VII and fibrinogen
Leukemoid reaction vs. CML
Leukemoid = incr. WBC, incr. Leukocyte alkaline phosphatase
CML = incr. WBC, decr. LAP
Hodgkin lymphoma
location in body
cells
associations
Localized, single group of nodes, contiguous spread
Reed-Sternberg cells
assoc. with EBV
non-Hodgkin lymphoma
location in body
cells
associations
Multiple, peripheral nodes
B cells
assoc. HIV and autoimmune disease
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
Non-Hodgkin T cell neoplasms
Adult T-cell lymphoma: caused by HTLV (assoc with IVDA)
Mycosis fungoides: cutaneous T-cell lymphoma
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
TdT+, CD10+
ALL markers (can have pre-B cell leukemia precursor)
most responsive to therapy
young people
CD20+, CD5+ B cell neoplasm
SLL/CLL
old people
TRAP stain positive B cell neoplasm
Hairy cell leukemia
Marrow fibrosis (leads to dry tap on aspiration)
Tx: cladribine
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)
t(9;22) translocation
CML, Philadelphia chromosome
Lytic bone lesions
Recurrent otitis media w/ mass involving mastoid bone
Langerhaans histiocytosis
S-100 marker, CD1a
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
Hemolytic-uremic syndrome (HUS)
Shiga toxin –> endothelial cell injury –> isolated activation of platelets –> RBC damage as they travel through narrrow lumens
Tumor suppressor genes
p53 (apoptosis inducer) Rb (regulates G1 to S checkpoint, phosphorylated/mutated = inactive) BRCA (DNA repair) APC (tumor suppressor) NF-1 (neurofibromatosis)
Protooncogenes
Ras (signal transduction) Erb-B1 (tyrosine kinase) Erb-B2/HER2 (tyrosine kinase) N-myc (neuroblastoma) C-myc (Burkitt, transcription activator)
Penetration of the basement membrane
- ) detachment of tumor cells (decr. E-cadherins)
- ) adhere to basement membrane (incr. laminin)
- ) invasion of BM (incr. metalloproteinases)
Cytokine mediator of cachexia
TNF-alpha
Factor V Leiden mechanism of pro-coagulation
increased coagulation (reduced susceptibility to cleavage) and decreased anticoagulation (decreased APC activity)
Oxidative stress is induced by…
Bactrim, dapsone, antimalarials, nitrofurantoin
fava beans
infection
Pure red cell aplasia (PRCA)
associated with thymoma, leukemia, parvovirus B19
