01a: Pathology Flashcards
1
Q
Mutations in Fas, leading to impaired (intrinsic/extrinsic) apoptosis pathway, results in:
A
Extrinsic;
Increased number of self-reacting lymphocytes (Fas-FasL interaction necessary in thymic medullary negative selection)
2
Q
Which proteins are pro-apoptotic in intrinsic pathway? And which are anti-apoptotic?
A
Pro: BAX, BAK
Anti: Bcl-2, Bcl-x
3
Q
Immune cells can play role in extrinsic pathway apoptosis by which actions?
A
T-Lymphocyte release of perforin and granzyme B (one extrinsic pathway for apoptosis)
4
Q
Key difference between necrosis and apoptosis is presence/absence of:
A
Inflammation (present in necrosis; intracellular components leak)
5
Q
In (X) necrosis, cell outlines are preserved, but nuclei disappear and there is high cytoplasmic binding of (Y) dyes.
A
X = coagulative Y = eosin
6
Q
Acute pancreatitis: what type of necrosis?
A
Fat (enzymatic; saponification aka damaged cells release lipase and liberated FAs bind Ca)
7
Q
Breast tissue trauma: what type of necrosis?
A
Fat (non-enzymatic/traumatic)
8
Q
Fibrinoid necrosis: mechanism of action
A
Fibrin combines with immune complexes (Type III HS) and damage vessel walls
9
Q
Cell injury: ribosomes detach from ER, indicating a (reversible/irreversible) injury.
A
Reversible
10
Q
Cell injury: lysosomes rupture, indicating a (reversible/irreversible) injury.
A
Irreversible (autolysis)
11
Q
Cell injury: mitochondrial vacuolization, a (reversible/irreversible) injury.
A
Irreversible (increased permeability)
12
Q
Mechanism behind cell and mitochondrial swelling in (reversible/irreversible) cell injury.
A
Reversible; low ATP means low activity of Na/K and Ca pumps
13
Q
Which signs in nucleus would lead you to believe cell injury is reversible?
A
Chromatin clumping; overall intact nucleus
14
Q
Which signs in nucleus would lead you to believe cell injury is irreversible?
A
Pyknosis (condensation), karyorrhexis (fragmentation), karyolysis (fading) of chromatin
15
Q
Brain regions most vulnerable to hypoxia/ischemia:
A
Watershed areas (ACA/MCA/PCA boundaries)
16
Q
Brain cells most vulnerable to hypoxia/ischemia:
A
- Purkinje cells of cerebellum
2. Pyramidal cells of hippocampus and neocortex
17
Q
Kidney regions most vulnerable to hypoxia/ischemia:
A
Medulla:
- Proximal tubule (straight segment)
- Thick ascending limb
18
Q
Zone (1/2/3) of liver is most vulnerable to hypoxia/ischemia.
A
3 (area around central v)
19
Q
Colon regions most vulnerable to hypoxia/ischemia:
A
Splenic flexure and rectum (watershed areas/border zones)
20
Q
Red, aka (X), infarct occurs in which tissues?
A
X = hemorrhagic
Those with multiple blood supplies (liver, lung intestine, testes)
21
Q
Reperfusion injury is an example of (X) infarct. What’s the mechanism behind this?
A
X = Red/hemorrhagic (REperfusion, REd)
Free radical damage (LIPID PEROXIDATION; irreversible mito injury, inflammation, complement activation)
22
Q
Pale, aka (X), infarct occurs in which tissues?
A
X = anemic
Solid organs with single (end-arterial) blood supply (heart, kidney, spleen)
23
Q
Key immune cell participants in acute inflammation:
A
- PMNs
- Eosinophils
- Mast cells
- Basophils
Also (pre-existing) Abs
24
Q
Key immune cell participants in chronic inflammation:
A
- Mononuclear cells (monocytes/macrophages, lymphocytes, plasma cells)
- Fibroblasts (blood vessel proliferation, fibrosis)
25
Aortic stenosis is an example of (dystrophic/metastatic) (X) deposition, which tends to occur in (normal/abnormal) tissues and is secondary to (Y).
Dystrophic
X = Ca
Abnormal
Y = injury/necrosis
26
Metastatic calcification tends to occur in (normal/abnormal) tissues, predominantly in (X). Why?
Normal
X = kidney interstitium, lung and gastric mucosa
These tissues lose acid quickly (high pH favors Ca deposition)
27
Patient with metastatic calcification of collecting ducts may develop:
Nephrogenic DI and renal failure
28
Metastatic calcification of tissues usually occurs secondary to:
1. Hypercalcemia (hyper-PTH, sarcoid)
| 2. High Ca-PO4 product levels (long-term dialysis, multiple myeloma, calciphylaxis)
29
Extravasation of leukocytes occurs predominantly at which part of vessel?
Post-cap venules
30
Deficiency of Sialyl-Lewis-X epitope results in defective:
Leukocyte margination/rolling (aka leukocyte adhesion deficiency type 2)
31
E and P selectins play important role in (margination/tight adhesion) of leukocytes. What is responsible for releasing/upregulating these selectins?
Margination/rolling
E: upregulated by TNF and IL1
P: released from weibel-palade bodies
32
ICAM and VCAM play important role in (margination/tight adhesion) of leukocytes. They interact with (X).
Tight adhesion;
| X = integrins (CD11/18; VLA-4)
33
Leukocyte adhesion deficiency type 1 is a result of decreased:
CD18 integrin subunit (interacts with ICAM)
34
(X) molecule responsible for diapedesis of WBCs.
X = PECAM-1
35
Key chemotactic products released to help guide leukocytes through interstitium.
C5a, IL-8, LTB4, Kallikrein, platelet-activating factor
36
Which vitamins serve as antioxidants?
ACE
37
Neonate with respiratory distress syndrome improves on treatment but then develops symptoms of rapid/labored breathing, wheezing, and perioral cyanosis. What likely happened?
Bronchopulmonary dysplasia (free radical injury due to prolonged mechanical ventilation)
38
Scar formation: (X)% of tensile strength regained at 3 months. Which ECM component required to increase this strength?
X = 70-80
| Collagen
39
T/F: Keloids are painful and pruritic.
True
40
Radiation for cancer treatment uses (UV/gamma) rays and works by which mechanisms?
Gamma and X-rays (ionizing radiation)
1. DNA double-strand breakage
2. Free radical formation (ionization of H2O and DNA/cell damage)
41
List the tissue mediators that stimulate angiogenesis in wound healing. What other functions do they have?
1. FGF and VEGF ("fruits and veggies"); no other roles
| 2. TGFb; fibrosis
42
PDGF is secreted by which cells?
Macrophages and platelets
43
PDGF roles in wound healing:
1. Vascular remodeling
2. Smooth muscle cell migration
3. Fibroblast growth (for collagen synthesis)
44
List the 3 phases of wound healing and the primary cells involved in each.
1. Inflammatory (platelets, PMNs, macros)
2. Proliferative (fibroblast, myofibroblast, endothelial cells, keratinocytes, macros)
3. Remodeling (fibroblasts)
45
Which stage of wound healing is delayed in both vit C and (X) deficiency?
X = Cu
Proliferative (deposition of type III collagen)
46
Remodeling stage of wound healing is delayed in (X) deficiency. What key event takes place in this stage?
X = Zn
Replacement of Type III Collagen by Type I (increasing tensile strength)
47
Pt with hx of severe burns on bilateral hands presents with inability to extend wrists due to significant scarring. This phenomenon is referred to as (X) and occurs in which stage of wound healing?
X = contracture (mediated by myofibroblasts)
Proliferative stage
48
List some auto-inflammatory vasculitides associated with granuloma formation
1. Granulomatosis with polyangiitis (Wegener's)
2. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
3. Giant cell (temporal) arteritis
4. Takayasu arteritis
49
How does the body handle retained foreign bodies (ex: sutures) or other foreign material (berylliosis, talcosis)?
Granuloma formation
50
Granuloma cell layers, from inside to outside.
1. Epithelioid macrophages
| 2. Lymphocytes and Multinucleated giant cells
51
Granuloma: (X) lymphocytes play key role by secreting (Y).
```
X = TH1
Y = IFN-gamma (activates macrophages)
```
52
Reason behind testing for (X) before anti-TNF drug is administered.
X = TB
TNFa (secreted by macros) induces/maintains granuloma formation so anti-TNF drugs can break down granuloma (disseminated disease)
53
AA female with dyspnea, cough, lymphadenopathy has hypercalcemia due to:
Sarcoidosis (granulomas have overactive 1-alpha hydroxylase, so high calcitriol production)
54
(Transudate/exudate) is high in protein and (high/low) in LDH.
Exudate (cellular fluid; cloudy)
| High
55
Fluid buildup in HF is (transudate/exudate). In lymphatic obstruction is (transudate/exudate). In nephrotic syndrome is (transudate/exudate).
Transudate (high hydrostatic P)
Exudate
Transudate (low oncotic P)
56
Fluid buildup in malignancy is (transudate/exudate) and in inflammation/infection is (transudate/exudate).
Exudate for both
57
Why does polycythemia vera present with (high/low) ESR?
Low;
| High number of RBCs "dilute" the inflammation products (fibrinogen) which serve as aggregation factors
58
T/F: Amyloidosis is the abnormal aggregation of proteins into disorganized, clumpy deposits in various tissues.
False - aggregate into linear beta-pleated sheets (insoluble fibrils)
59
AL amyloidosis involves deposition of (X). AA involves deposition of (Y).
```
X = Ig light chains (primary; multiple myeloma)
Y = Amyloid A (secondary; chronic inflammatory conditions like RA, IBD)
```
60
Heritable form of amyloidosis due to (X) mutation
X = transthyretin
61
Senile amyloidosis is due to (X) deposition, primarily in which tissue(s)?
```
X = normal transthyretin
Cardiac ventricles (restrictive cardiomyopathy)
```
62
List some examples of organ-specific amyloid deposition
1. AD (most important; beta amyloid)
2. Pancreatic islets (DM II; amylin)
3. Thyroid medullary carcinoma
4. Atrial amyloidosis (increased risk of Afib; ANP)
63
Lipofuscin is seen in (X) condition and is formed from:
```
X = normal aging
Lipid oxidization (yellow/brown, wear and tear pigment)
```
64
T/F: Normal aging involves increase in heart chamber sizes.
False - decrease LV chamber (septum acquires sigmoid shape) and myocardial atrophy
65
Define "anaplasia" and "neoplasia"
A: Complete lack of differentiation of cells in malignant neoplasm
N: Uncontrolled, clonal proliferation (benign or malignant)
66
Multi-nucleated giant cells in tumor are marker for (metaplasia/dysplasia/anaplasia/neoplasia).
Anaplasia
67
T/F: Invasive carcinoma involves over-expression of E-cadherin to allow neoplastic cell adhesion and invasion of BM.
False - increase expression of laminin for this purpose; inactivate E-cadherin to decrease cell-cell contact
68
In most cases, tumor (stage/grade) holds more prognostic value.
Grade (degree of differentiation/mitotic activity);
TNM staging more important for some cancers (ex: colon)
69
T/F: Lymphoma is benign, leukemia is malignant.
False - both malignant
70
Malignant version of hemangioma:
Angiosarcoma
71
Three most common cancers in children, in order of incidence
1. Leukemia
2. Brain/CNS
3. Neuroblastoma
Same order for cancer mortality
72
Sign of Leser-Trelat:
Sudden outbreak of multiple seborrheic keratoses (indication of GI/visceral malignancy)
73
(X) carcinomas present with hypo-PTH hypercalcemia via which mechanism?
```
X = squamous cell (lung, H/N, and others)
PTHrP secretion (increase bone resorption and decrease renal excretion of Ca)
```
74
Endocrine-related paraneoplastic syndromes associated with small cell lung cancer:
1. SIADH
| 2. Cushing's (high ACTH)
75
Pure red cell aplasia is neoplastic syndrome associated with (X). What are the Sx and what's the mechanism?
X = thymoma
Anemia with low retic count but normal WBC, platelets (absence only of erythroid precursors in bone marrow)
MOA: inhibition of precursors by IgG auto-Ab or cytotoxic T-cells
76
Presence/simultaneous onset of anterior mediastinal mass and recurrent sinopulmonary infections in an adult is likely due to:
Thymoma with Good (paraneoplastic) Syndrome (hypogammaglobulinemia and immunodeficiency)
77
(X) syndrome: migratory superficial thrombophlebitis, an early sign of (Y) cancer.
```
X = Trousseau
Y = Adenocarcinoma (esp pancreatic) that produce thromboplastin-like substance
```
78
Myasthenia gravis can be a paraneoplastic syndrome in which cancer(s)?
Thymoma
79
"Dancing eyes, dancing feet" in child indicates which underlying malignancy? And in adults?
Paraneoplastic syndrome (opsoclonus-myoclonus ataxia)
C: neuroblastoma
A: small cell lung cancer
80
65 yo patient with lung cancer develops dizziness, limb/trunk ataxia, visual disturbances. Which paraneoplastic syndrome? And which lung cancer?
Paraneoplastic cerebellar degeneration (Ab against purkinje cells)
Small cell
81
65 yo lifetime smoker with SOB/cough, weight loss. Difficulty rising from chair, dysphagia, and dry mouth.
Small cell lung cancer with Lambert Eaton myasthenic syndrome (Ab against pre-synaptic Ca channel, decrease ACh release)
82
JAK2 is (oncogene/tumor suppressor) with (X) gene product. Implicated in which cancers?
Oncogene
X = non-R (cytoplasmic) tyrosine kinase
Chronic myeloproliferative disorders (ET, PCV, 1o myelofibrosis)
83
APC is (oncogene/tumor suppressor) with (X) gene product. Implicated in which cancers?
Tumor suppressor
X = negative regulator of beta-catenin/WNT path
Colorectal (associated with FAP)
84
BRCA1/2 are (oncogenes/tumor suppressors) with (X) gene product. Implicated in which cancers?
Tumor suppressors
X = DNA ds break repair proteins
Breast, ovarian, pancreatic
85
MEN1, associated with (X) gene mutation:
X = MEN1 (tumor suppressor)
1. Pancreatic endocrine tumors (ZES, insulinoma, VIPomas, glucagonoma)
2. Pituitary adenoma (prolactin, GH)
3. Parathyroid adenoma
86
NF1 on chromosome (X) and NF2 on chromosome (Y).
```
X = 17
Y = 22
```
87
Rb is (oncogene/tumor suppressor) that inhibits (X), unless modified via (Y).
Tumor suppressor
X = E2F (thus inhibits G1 to S transition)
Y = phosphorylation
88
Multiple malignancies at early age associated with (X) syndrome, (Y) mutation, and thus impaired (Z).
```
X = Li Fraumeni (SBLA cancer: Sarcoma, Breast, Leukemia, Adrenal)
Y = TP53 (p53)
Z = apoptosis
```
89
MEN2A, associated with (X) gene mutation:
X = RET (oncogene)
1. Pheochromocytoma
2. Parathyroid hyperplasia
3. Medullary thyroid cancer
90
MEN2B, associated with (X) gene mutation:
X = RET (oncogene)
1. Pheochromocytoma
2. Medullary thyroid cancer
3. Mucosal neuromas
91
HTLV-1 microbe associated with which cancer?
Adult T cell leukemia/lymphoma
92
Clonorchis sinensis (liver fluke) associated with which cancer?
Cholangiocarcinoma
93
Schistosomiasis associated with which cancer?
Squamous cell bladder
94
How does one's genetic profile determine his/her susceptibility to chemical carcinogens?
Most enter body as pro-carcinogens and are activated by CYP450 (microsomal monooxygenase), and activity of these enzymes is genetically determined
95
Aromatic amines are carcinogens that predispose to which type of cancer? And nitrosamines?
Aromatic: Transitional cell carcinoma (bladder)
| Nitros (smoked food): gastric
96
Asbestos associated with (X) cancer.
X = bronchogenic carcinoma (way more than, but as well as, mesothelioma)
97
Cigarette smoke increases risk for which cancers?
1. Larynx (squamous)
2. Esophagus (squamous, adeno)
3. Lung (squamous, SCLC)
4. Kidney (RCC)
5. Pancreas (adeno)
6. Bladder (transitional cell)
7. Cervix (carcinoma)
98
Ethanol increases risk for which cancers?
1. Esophagus (squamous)
| 2. Liver
99
Ionizing radiation increases risk for which cancers?
Thyroid (papillary thyroid carcinoma)
100
Second leading cause of lung cancer after cigarette smoke.
Radon exposure
101
Both arsenic and vinyl chloride exposure increase risk for which cancer?
Angiosarcoma of liver
102
Psammoma bodies are seen in which cancers?
PSaMMoma
1. Papillary thyroid carcinoma
2. Serous papillary cystadenoma of ovary
3. Mesothelioma
4. Meningioma
103
MDR1 (multidrug resistance protein 1), aka (X), is seen in (Y) cells and functions to:
```
X = P-glycoprotein
Y = cancer (classically in adrenocortical carcinoma)
```
ATP-dependent efflux pump (pumps out chemo agents; mechanism of resistance to drugs over time)
104
Mechanism of cachexia in chronic disease:
TNFa (cachectin; acts on hypothalamus to suppress appetite and increase BMR)
Also IFN-gamma, IL1, IL6
105
Most carcinomas spread via (blood/lymph) and most sarcomas spread via (blood/lymph). List the four key exceptions.
Lymph; blood
FCRH (Four Carcinomas Route Hematogenously):
1. Follicular thyroid
2. Choriocarcinoma
3. RCC
4. Hepatocellular
106
If you were to bet on the origin of a liver met, what would you bet on?
Colon
107
CA 15-3/CA27-29 tumor markers for:
Breast cancer
108
CA 19-9 tumor marker for:
Pancreatic adenocarcinoma
109
CA 125 tumor marker for:
Ovarian cancer
110
CEA tumor marker for:
Colorectal and pancreatic cancers mainly (nonspecific); in colorectal, indicates worse prognosis or recurrence
111
Chromogranin tumor marker for:
Neuroendocrine tumors
