Patho: Genetics, Immuno, Neoplasia Flashcards
1
Q
- most common chromosomal disorder
- flat facial profile, oblique palpebral fissures and epicanthal folds
- non-disjunction of Ch 21 during meiosis
A
Trisomy 21 (Down’s Syndrome)
2
Q
-prominent occiput, micrognathia, short neck, overlapping fingers, cardiac, renal, rocker-bottom feet
A
Trisomy 18 (Edward Syndrome)
3
Q
cardiac anomalies, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia
A
DiGeorge Syndrome (CATCH 22)
4
Q
- > = 2 X chromosome, >= 1 Y chromosome (most common: 47XXY)
- reduced spermatogenesis, male infertility
testicular atrophy, micropenis
A
Klinefelter Syndrome
5
Q
- complete or partial X chromosome monosomy (45XO)
- ovarian streaks, absent 2° sex char., short stature, cystic hygromas (esp. neck)
A
Turner Syndrome
6
Q
- 2nd most common cause of mental retardation (following Down’s)
- CGG expansion (FMR1 gene of X chromosome)
(+) macroorchidisim
A
Fragile X Syndrome
7
Q
- Autosomal dominant neurodegenerative disorder
- CAG expansion (HTT gene, Ch 4)
A
Huntington Disease
8
Q
- deletion in paternally derived Ch 15
- MR, hypotonia, hyperphagia, obesity, hypogonadism
A
Prader-Willi Syndrome
9
Q
- deletion in maternally derived Ch 15
- MR, ataxic gait, sz, inappropriate laughter (“happy puppet”)
A
Angelman Syndrome
10
Q
- Caused by activation of Th2 CD4+ T cells, leading to production of IgE
- Anaphylaxis, BA/AR, food allergies
vascular dilation, smooth muscle contraction, mucus production
A
Type I HSR
Immediate, IgE-mediated
11
Q
- Caused by antibodies binding to fixed tissue and cell antigens
- AIHA, ITP, Pemphigus vulgaris, Goodpasture, Rehumatic fever, MG, Graves, Pernicious Anemia
A
Type II HSR
Antibody-mediated
12
Q
- Caused by antibodies binding to antigens, which circulate and may deposit in vascular beds, stimulating inflammation secondary to complement activation
- Inflammation, necrotizing vasculitis, fibrinoid necrosis
- SLE, PSGN, PAN, serum sickness
A
Type III HSR
Immune-complex-mediated
13
Q
- Caused by a cell-mediated immune response in which T lymphocytes cause tissue injury through cytokine production, inflammation, macrophage activation, direct cell killing
- perivascular cellular infiltrates, edema, granuloma formation, cell destruction
- RA, MS, T1DM, IBD, Psoriasis
A
Type IV HSR
T-cell mediated
14
Q
most common autoantibody in SLE
most specific autoantibodies for SLE
A
sens: ANA
spec: anti-Sm, anti-dsDNA
(anti-dsDNA correlates with disease activity)
15
Q
drugs that may cause drug-induced lupus
associated with anti-histone
A
hydralazine
isoniazid
procainamide
penicillamine
16
Q
classes of lupus nephritis
A
I - minimal mesangial II - mesangial proliferative III - focal IV - diffuse (most common! wire-loop appearance of capillaries) V - membranous VI - advance sclerosing
17
Q
- dry eyes, dry mouth, autoimmune mediated destruction of lacrimal and salivary glands
- type IV HSR
- lip biopsy: acinar atrophy, fibrosis, hyalinization
- Anti-Ro, Anti-La
A
Sjogren Syndrome
18
Q
- chronic inflammation, widespread small vessel damage, progressive interstitial and perivascular fibrosis in the skin and organs
- skin: sclerotic atrophy
- blood vessels: thickening of basal lamina, endothelial damage, partial occlusion
- GIT - atrophy, fibrosis of muscularis, rubber-hose-like inflexibility (esophagus)
- MSK: hypertrophy/plasia of synovial tissues
- renal: intimal thickening, proliferation
- lung: interstitial fibrosis
- heart: pericarditis/effusion, myocardial fibrosis, thickening of intramyocardial arterioles
A
Scleroderma (systemic sclerosis)
- diffuse scleroderma (anti-DNA topoisomerase I)
- limited scleroderma (anti-centromere)
19
Q
CREST syndrome found in?
Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
A
Limited cutaneous systemic sclerosis (limited scleroderma)
- anti-centromere (vs diffuse, anti-DNA topoisomerase I)
20
Q
Type of Kidney Rejection with
- cyanotic, mottled, flaccid kidney
- thrombotic occlusion of capillaries, fibrinoid necrosis of arterial walls
A
Hyperacute Rejection (pre-formed anti-donor antibodies)
21
Q
Type of Kidney Rejection with
- signs of renal failure
- [Type I, TI] tubulointerstitial infiltrates (tubulitis)
- [Type II, vascular] swollen endothelial cells with lymphocytes (endothelitis)
A
Acute Cellular Rejection (T-cell mediated)
22
Q
Type of Kidney Rejection with
- signs of renal failure
- inflammation of glomeruli and peritubular capillaries, focal thrombosis of small vessels
A
Acute Antibody-mediated Rejection
Ig’s produced post-transplantation
23
Q
Type of Kidney Rejection with
- gradual rise of crea
- vascular: intimal inflammation, glomerulopathy w/ duplication of BM, peritubular cappilaritis
- interstitial fibrosis, tubular atrophy, loss of renal parenchyma
A
Chronic Rejection
24
Q
- XLR: disturbance of early T-lymphocyte development due to cytokine receptor defect
- AR: impaired DNA synthesis due to adenosine deaminase deficiency
- T-cells more decreased than B-cells, but antibody production ↓ due to loss of T-cell help
- prominent oral thrush, morbiliform rash due to GVHD
A
Severe Combined Immunodeficiency
25
- XLR: Btk gene defect, needed for B-cell development
- absent germinal centers in lymphoid tissues
- symptomatic at about 5-6 months after maternal antibody depletion
Bruton Agammaglobulinemia
26
- XLR
- triad: thrombocytopenia, infections (immunodeficiency), eczema
- t-cells in thymus are normal, but depleted elsewhere; ↓IgM, normal IgG, ↑IgA and IgE (paradoxical)
Wiskott-Aldrich Syndrome
27
- maturation defect in B cells causing impaired IgA production
- recurrent infections
Selective IgA deficiency
28
HIV proteins:
- attaches to CDR and CXCR4/CCR5
- fusion protein
gp120
| gp41
29
HIV pathologic findings
- CD4 T-cell depletion
- germinal B-cell hyperplasia, bone marrow plasmacytosis → hypergammaglobulinemia and IC deposition
- infected monocytes → CNS infection of microglia
30
AIDS defining illnesses
< 1000 - lymphoma, TB, Kaposi Sarcoma, zoster
< 200 - PCP, candidiasis
< 100 - Cryptococcosis, mucosal herpes simplex
< 50 - CMV, MAC, Toxoplasmosis, Cryptosporidosis
31
Associated with HIV,
- most common fungal infection
- most common type of lymphoma
- sarcoma
- candidiasis
- B-cell lymphoma
- Kaposi Sarcoma (HHV 8)
32
Top 3 cancers in CHILDREN
ALL > CNS > Burkitt Lymphoma
33
Top 3 cancers in MALES
Prostate > Lung > Colorectal
Top 3 mortalities: Lung > Prostate > Colorectal
34
Top 3 cancers in FEMALES
Breast > Lung > Colorectal
Top 3 mortalities: Lung > Breast > Colorectal
35
Most commonly mutated proto-oncogene in human cancers
RAS
36
Tumor suppressor gene that controls the G1-S checkpoint ("guardian of the cell cycle")
Rb
| recall: inactivation by E7 of HPV
37
Tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence and apoptosis ("guardian of the genome")
p53
| recall: inactivation by E6 of HPV
38
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Proto-oncogenes and associated CA's
RAS
EGFR
HER2
JAK 2
ABL
BRAF
MYC
CDK4
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RAS - many (most common)
EGFR - lung
HER2 - breast
JAK 2 - PC, ET, PMF
ABL - CML
BRAF - Hairy cell leukemia
MYC - Burkitt, neuroblastoma
CDK4 - glioblastoma
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39
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Commonly mutated TSGs and associated CA's
Rb
p53
APC
E-cadherin
PTEN
NF1/2, WT1, VHL
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Rb - retinoblastoma
p53 - many cancers
APC - FAP, colorectal CA
E-cadherin - gastric CA diffuse type, invasive lobular breast CA
PTEN - breast, edometrial
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40
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Physical/Chemical Exposures and associated CA's
Smoking
Alcohol
Estrogen
Arsenic
Asbestos
Benzene
Nitrosamine
Cadmium
Vinyl chloride
```
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Smoking - oral cavity, pharynx, larynx, esophagus (sq), lung (sq, sc), pancreas (adeno), renal cell
Alcohol - hepatocellular
Estrogen - endom, breast
Arsenic - skin scca, liver angiosarcoma
Asbestos - lung, mesothelioma
Benzene - AML
Nitrosamine - esophagus, gastric (Japan)
Cadmium - prostate
Vinyl chloride - liver angiosarcoma
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