Pathology Flashcards
(121 cards)
1
Q
Neurons most vulnerable to hypoxic-ischemic insults include
A
Purkinje cells of the cerebellum and
pyramidal cells of the hippocampus and neocortex (zones 3, 5, 6).
2
Q
Red infarct
A
liver, lung, intestine, testes
LITL
3
Q
Free radicals damage cells via
A
membrane lipid peroxidation, protein modification, DNA breakage.
4
Q
Free radicals are produced via:
A
radiation exposure (eg, cancer therapy) metabolism of drugs (phase I) redox reactions nitric oxide (eg, inflammation) transition metals WBC (eg, neutrophils, macrophages) oxidative burst
MR! MR! WoN!
5
Q
Free radicals can be eliminated by
A
Protein metal carriers (eg, transferrin, ceruloplasmin).
Antioxidants (eg, vitamins A, C, E)
Spontaneous decay
Enzymes (scavenging) (eg, catalase, superoxide dismutase, glutathione peroxidase)
PASE
6
Q
Dystrophic calcification
A
fat necrosis
abscesses
infarcts
liquefactive necrosis
atherosclerotic plaques
thrombi
congenital CMV rubella schistosomiasis TB (lung and pericardium) and other granulomatous infections toxoplasmosis CREST syndrome
psammoma bodies
FAIL AT CREST momma!
7
Q
Lipofuscin locations
A
heart, colon, liver, kidney, eye, and other organs.
KLECH
8
Q
Localized Amyloidosis
A
A- Alzheimer disease (beta-amyloid protein)
D - Diabetes mellitus (Type 2) -Islet amyloid polypeptide (IAPP)
A - atrial amyloidosis - Isolated (ANP )
M - Medullary thyroid cancer - Calcitonin (A Cal)
S - Systemic Senile (age-related) amyloidosis [Normal (wild-type)transthyretin (TTR)]
ADAM’S amyloid
9
Q
Histamine causes
A
Rubor (redness) and calor (warmth)
Tumor (swelling)
Dolor (pain)
“triple positive”
10
Q
Bradykinin causes
A
Rubor (redness) and calor (warmth)
Dolor (pain)
11
Q
NO cause
A
Rubor (redness) and calor (warmth)
12
Q
Prostaglandins cause
A
Rubor (redness) and calor (warmth)
Dolor (pain) (PGE2)
13
Q
Seratonin + Leukotrians cause
A
Tumor (swelling)
14
Q
Fever explain process
A
Pyrogens (eg, LPS) induce macrophages to release IL-I and TNF -> inc COX activity in perivascular cells of the hypothalamus -> inc PGE2 -> inc temperature set point.
15
Q
Acute phase reactants
UPREGULATED
A
Ferritin Fibrinogen SAA Hepcidin CRP
More Fn FiSH in the C! (sea).
16
Q
Acute phase reactants
DOWNREGULATED
A
Albumin
Transferrin
17
Q
Erythrocyte sedimentation rate increased by
A
Most anemias
Infections
information (eg, giant cell [temporal] arteritis,
polymyalgia rheumatica)
Cancer (eg, metastases, multiple myeloma)
Renal disease (end-stage or nephrotic syndrome)
Pregnancy
Inflammation and infection CRAP
18
Q
Erythrocyte sedimentation rate decreased by
A
Sickle cell anemia (altered shape) Polycythemia (Inc RBCs "dilute" aggregation factors) HF Microcytosis hypoFibrinogenemia
Shape Size Amount and FF
19
Q
Acute inflammation mediators
A
I - Inflammasome
M - mast cells
T - Toll-like receptors
A - arachidonic acid metabolites
N - neutrophils
ned
in the
B - basophils E - eosinophils A - antibodies (preexisting) C - complement H - Hageman factor (factor XII)
20
Q
Acute inflammation outcome
A
S - Scarring
C -Chronic inflammation (antigen presentation by macrophages and other APCs - activation of CD4+ Th cells)
R - Resolution and healing (IL-10, TGF-beta)
A - Abscess (acute inflammation walled off by fibrosis)
P - Persistent acute inflammation (IL-8)
21
Q
Leukocyte extravasation steps
A
Margination and rolling -> Tight binding (adhesion) -> Diapedesis (transmigration) -> Migration.
22
Q
Margination and rolling defective in
A
leukocyte adhesion deficiency type 2 (dec. Sialyl Lewis X)
23
Q
Tight binding (adhesion) defective in
A
leukocyte adhesion
deficiency type I (dec. CDl8
integrin subunit)
24
Q
Margination and rolling molecules: location and target - Sialyl LewisX
A
on: LEUKOCYTE
binds:
E-selectin (upregulated by TNF and IL-I)
P-selectin (released from Weibel Palade bodies)
on: VASCULATURE/STROMA
25
Margination and rolling molecules: location and target - L-selectin
on: LEUKOCYTE
binds: GlyCAM-1, CD34 on VASCULATURE/STROMA
26
Tight binding (adhesion) molecules: location and target -ICAM-1 (CD54)
on:VASCULATURE/STROMA
binds: CDll/18 integrins
(LFA-1, Mac-I) on LEUKOCYTE
27
Tight binding (adhesion) molecules: location and target - VCAM-1 (CDI06)
on: VASCULATURE/STROMA
binds: VLA-4 integrin on LEUKOCYTE
28
Diapedesis (transmigration) WBC molecules: location and target - PECAM-1 (CD31)
on: VASCULATURE/STROMA
binds: PECAM-1 (CD31) on LEUKOCYTE
29
Migration - molecules: location and target - chemotactic signals
on: VASCULATURE/STROMA
Chemotactic factors: C5a, IL-8, LTB4, kallikrein, platelet-activating
factor
30
CD# of GlyCAM-1
CD34
31
CD# of PECAM-1
CD31
32
CD# of VCAM-1
CDI06
33
CD# of ICAM-1
CD54
34
CD# of LFA-1, Mac-I
CDll/18 integrins
35
Chronic inflammation OUTCOMES
Scarring, amyloidosis, and neoplastic transformation
| SAN
36
Chronic inflammation STIMULI
```
Persistent infections (eg, TB, T pallidum, certain fungi, and viruses) - type IV hypersensitivity,
autoimmune diseases, prolonged exposure to toxic agents (eg, silica) and foreign material.
```
Things that are not supposed to be there.
37
Wound healing MEDIATORS - FGF mediates
Stimulates angiogenesis
38
Wound healing MEDIATORS - TGF beta mediates
Angiogenesis, fibrosis
39
Wound healing MEDIATORS - VEGF mediates
Stimulates angiogenesis
40
Wound healing MEDIATORS - PDGF mediates
- Induces vascular remodeling
- smooth muscle cell migration
- Stimulates fibroblast growth (for collagen synthesis)
41
Wound healing MEDIATORS - Metalloproteinases mediates
Tissue remodeling
42
Wound healing MEDIATORS - EGF mediates
Stimulates cell growth via tyrosine kinases (eg, EGFR/ErbBl)
43
PDGF Secreted by
activated platelets and macrophages
44
PHASE OF WOUND HEALING - Proliferative (day 3-weeks after wound)
EFFECTOR CELLS.
Fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages.
45
Granulomatous inflammation infections ETIOLOGIES
```
• Bacterial: Mycobacteria (tuberculosis,
leprosy), Bartonella henselae (cat scratch
disease; stellate necrotizing granulomas),
Listeria monocytogenes (granulomatosis
infantiseptica), Treponema pallidum
(3° syphilis)
• Fungal: endemic mycoses (eg,
histoplasmosis)
• Parasitic: schistosomiasis
```
BLT w/ MAYO and Mushroom for SHIZEL!
46
Granulomatous inflammation NON-infections ETIOLOGIES in general:
Immune-mediated
Vasculitis
Foreign material
Chronic granulomatous disease
47
Granulomatous inflammation NON-infections ETIOLOGIES - Immune-mediated:
sarcoidosis, Crohn disease, 1° biliary cholangitis, subacute (de Quervain /granulomatous) thyroiditis
Sick Chicks Big Tits
48
Granulomatous inflammation NON-infections ETIOLOGIES (Vasculitis):
Granulomatosis with polyangiitis (Wegener)
Eosinophilic granulomatosis with polyangiitis (Churg Strauss)
Giant cell (temporal) arteritis
Takayasu arteritis
49
Granulomatous inflammation NON-infections ETIOLOGIES (Foreign material):
berylliosis
talcosis
hypersensitivity pneumonitis
50
Types of collagen in Hypertrophic and Keloid
Hypertrophic: 3
Keloid: 1 & 3
51
Hallmarks of cancer - in general, the 3 subtypes:
Growth, Don't die, Tissue changes.
52
Hallmarks of cancer - Growth
| It generally consists of...
Growth signal self-sufficiency
Anti-growth signal insensitivity
53
Hallmarks of cancer - Don't die
| It generally consists of...
Evasion of apoptosis
Limitless replicative potential
54
Hallmarks of cancer - Tissue changes
| It generally consists of...
Sustained angiogenesis
Tissue invasion
Metastasis
Warburg effect
55
Growth signal self-sufficiency:
Mutations in genes encoding:
• Proto-oncogenes - t growth factors - autocrine loop (eg, inc. PDGF in brain tumors)
• Growth factor receptors - constitutive signaling (eg, HER2/neu in breast cancer)
• Signaling molecules (eg, RAS}
• Transcription factors (eg, MYC)
• Cell cycle regulators (eg, cyclins, CDKs)
56
Anti-growth signal insensitivity:
* Mutations in tumor suppressor genes (eg, Rb}
| * Loss of E-cadherin function - loss of contact inhibition (eg, NF2 mutations}
57
Evasion of apoptosis:
Mutations in genes that regulate apoptosis (eg, TP53, BCL2 - follicular B cell lymphoma).
58
Limitless replicative potential:
Reactivation of telomerase - maintenance and lengthening of telomeres - prevention of
chromosome shortening and cell aging.
59
Sustained angiogenesis
Inc. pro-angiogenic factors (eg, VEGF} or dec. inhibitory factors. Factors may be produced by tumor or stromal cells.
Vessels can sprout from existing capillaries (neoangiogenesis}
Endothelial cells are recruited from bone marrow (vasculogenesis).
Vessels may be leaky and/or dilated.
60
Tissue invasion
Loss of E-cadherin function - loosening of intercellular junctions - metalloproteinases degrade
basement membrane and ECM - cells attach to ECM proteins (eg, laminin, fibronectin} - cells
migrate through degraded ECM (" locomotion"} - vascular dissemination.
61
Metastasis
Tumor cells or emboli spread via lymphatics or blood - adhesion to endothelium - extravasation and homing. The site of metastasis can be predicted by the site of the primary tumor, as the target organ is often the first-encountered capillary bed ("seed and soil" theory). Some cancers show organ tropism (eg, lung cancers commonly metastasize to adrenals).
62
Warburg effect
The shift of glucose metabolism away from mitochondrial oxidative phosphorylation toward glycolysis.
63
Immune evasion in cancer
* Dec. MHC class I expression by tumor cells - cytotoxic T cells are unable to recognize tumor cells.
* Tumor cells secrete immunosuppressive factors (eg, TGF-beta) and recruit regulatory T cells to down-regulate immune response.
* Tumor cells up-regulate immune checkpoint molecules, which inhibit the immune response.
64
Antibodies targeting PD-1
Nivolumab
| Pembrolizumab
65
Antibodies targeting PD-L1/2
Atezolizumab
Durvalumab
Avelumab
66
Antibody targeting CTLA-4
Ipilimumab
67
CTLA-4 on T cells outcompetes CD28 for
B7 on APCs
68
CD# of B7
80/86
69
These tumors metastasize to the brain
Lung> breast > melanoma, colon, kidney.
70
These tumors metastasize to the Liver
Colon >> Stomach > Pancreas (Cancer Sertintly Penetrates).
71
These tumors metastasize to the Bone
Prostate, Breast> Kidney, Thyroid, Lung
PB/KTL
```
Prostate - Blastic
Breast - Mixed
Kidney - Lytic
Thyroid - Lytic
Lung - Lytic + blastic
```
72
BCR-ABL
JAK2
GENE PRODUCT
Non-receptor tyros ine kinase
73
BRAF GENE PRODUCT
Serine/threonine kinase
74
BCL-2 GENE PRODUCT
Antiapoptotic molecule (inhibits apoptosis)
75
c-KIT GENE PRODUCT
CytoKlne receptor
76
KRAS GENE PRODUCT
GTPase
77
BRAF ASSOCIATED NEOPLASM
Ly - lymphoma (NON-Hodgkin )
M - Melanoma
P - papillary thyroid carcinoma
H - hairy cell leukemia
78
BCL-2 ASSOCIATED NEOPLASM
Follicular and diffuse large B Cell Lymphomas
79
c-KIT ASSOCIATED NEOPLASM
Gastroi ntestinal stromal tumor (GIST)
80
KRAS ASSOCIATED NEOPLASM
C - Colon cancer
L - lung cancer
i
P - pancreatic cancer
81
RET
ALK
HER2/neu (c-erbB2)
Receptor tyrosine kinase
82
RET
MEN 2A and 2B, papillary thyroid carcinoma
83
ALK
Lung Adenocarcinoma (Adenocarcinoma of the Lung Kinase)
84
HER2/neu (c-erbB2)
Breast and gastric carcinomas
BiG
85
PTEN GENE PRODUCT
Negative regulator of P13k/AKT pathway
86
PTEN ASSOCIATED CONDITION
Breast, prostate, and endometrial cancer
87
APC GENE PRODUCT
Negative regulator of beta-catenin/WNT pathway
88
CDKN2A GENE PRODUCT
p16, blocks G1 -> S phase
89
CDKN2A ASSOCIATED CONDITION
Melanoma, pancreatic cancer
90
BRCA1/BRCA2 GENE PRODUCT & ASSOCIATED CONDITION
DNA repair protein
Breast, ovarian, and pancreatic cancer
BOP
91
NF1 GENE PRODUCT & ASSOCIATED CONDITION
Neurofibromin (Ras GTPase activating protein)
| Neurofibromatosis is type 1
92
VHL GENE PRODUCT
Inhibits hypoxia-inducible factor la
93
Cigarette smoke Carcinogen cause
```
R - Renal cell carcinoma: Kidney
A - adenocarcinoma (Pancreas)
T - Transitional cell carcinoma: Bladder
S - Squamous cell carcinoma: CELL
Cervix
Esophagus
Larynx
Lung (+small cell)
```
94
Alkaline phosphatase IMPORTANT ASSOCIATIONS
Metastases to bone or liver, Paget disease of bone, seminoma (placental ALP).
Exclude hepatic origin by checking LFTs and GGT.
95
a -fetoprotein IMPORTANT ASSOCIATIONS
```
Hepatocellular carcinoma
Endodermal sinus (yolk sac) tumor
Mixed germ cell tumor
Ataxia-telangiectasia
Neural tube defects.
(HE-MAN is the alpha male!)
```
Normally made by the fetus. Transiently elevated in pregnancy. High levels associated with neural tube and abdominal wall defects, low levels associated with Down syndrome.
96
Calcitonin IMPORTANT ASSOCIATIONS
Medullary thyroid carcinoma (alone and in MEN2A, MEN2B).
97
hCG IMPORTANT ASSOCIATIONS
hydatidiform moles
Choriocarcinomas (gestational trophoblastic disease),
Gonadal - testicular cancer
Mixed germ cell tumor.
hCG Matters
98
Radon EXPOSURE & IMPACT
A by-product of uranium decay, and accumulates in basements.
Lung cancer (2nd leading cause after cigarette smoke)
99
GFAP STAIN
NeuroGlia (eg, astrocytes, Schwann cells, oligodendrocytes) -> Astrocytoma, Glioblastoma
100
S-100 STAIN
Neural crest cells -> Melanoma, schwannoma, Langerhans cell histiocytosis
101
Vimentin STAIN
Mesenchymal tissue (eg, fibroblasts, endothelial cells, macrophages) -> Mesenchymal tumors (eg, sarcoma), but also many other tumors (eg, endometrial carcinoma, renal cell carcinoma, meningioma)
102
P-glycoprotein
Also known as multidrug resistance protein I (MDRI). Classically seen in adrenocortical carcinoma but also expressed by other cancer cells (eg, colon, liver). Used to pump out toxins, including chemotherapeutic agents (one mechanism of dec. responsiveness or resistance to chemotherapy over time).
103
Psammoma bodies are seen in:
```
S - Somatostatinoma
y
M - Malignant Mesothelioma
P - Prolactinoma
T - thyroid (Papillary carcinoma)
O - Ovarian serous papillary cystadenocarcinoma
M - Meningioma
```
104
Paraneoplastic syndromes of Small cell lung cancer
ACTH
ADH
Paraneoplastic Encephalomyelitis - Antibodies against Hu antigens in neurons.
Lambert-Eaton myasthenic syndrome - Antibodies against presynaptic (P/Q-type) Ca2+ channels at NMJ.
Paraneoplastic Cerebellar degeneration - Antibodies against antigens in Purkinje cells
Opsoclonus- myoclonus ataxia
A/C ALOE
105
Dermatomyositis MOST COMMONLY ASSOCIATED TUMOR(S)
Adenocarcinomas, especially ovarian
106
Acanthosis nigricans & Sign of Leser-Trelat MOST COMMONLY ASSOCIATED TUMOR(S)
Gastric adenocarcinoma and other visceral malignancies
107
Hypertrophic osteoarthropathy
| MOST COMMONLY ASSOCIATED TUMOR(S)
Adenocarcinoma of the lung
108
Hypertrophic osteoarthropathy
| DESCRIPTION/MECHANISM
Abnormal proliferation of skin and bone at distal extremities -> clubbing, arthralgia, joint effusions, periostosis of tubular bones.
109
Paraneoplastic syndromes of Thymoma
Pure red cell aplasia - Anemia with low reticulocytes
Good syndrome - Hypogammaglobulinemia
Myasthenia gravis - Antibodies against postsynaptic ACh receptors at NMJ.
110
```
Nonbacterial thrombotic (marantic) endocarditis
DESCRIPTION/MECHANISM
```
Deposition of sterile platelet thrombi on heart valves
111
```
Nonbacterial thrombotic (marantic) endocarditis
MOST COMMONLY ASSOCIATED TUMOR(S)
```
Adenocarcinomas, especially pancreatic
112
Polycythemia
| DESCRIPTION/MECHANISM & MOST COMMONLY ASSOCIATED TUMOR(S)
Inc. Erythropoietin
```
Pheochromocytoma
Renal cell carcinoma (kidney)
HCC (Liver)
Hemangioblastoma
Leiomyoma (Uterine)
```
Pheo HULK
113
Inc. PTHrP
| MOST COMMONLY ASSOCIATED TUMOR(S)
Squamous cell carcinomas of the lung, head, and neck .
Renal, bladder.
Breast, and ovarian carcinomas.
114
1,25-(OH)2 vitamin D3 (calcitriol)
| MOST COMMONLY ASSOCIATED TUMOR(S)
Lymphoma
115
Anti-NMDA receptor encephalitis
| MOST COMMONLY ASSOCIATED TUMOR
Ovarian teratoma
116
Anti-NMDA receptor encephalitis
| DESCRIPTION/MECHANISM
```
L - language dysfunction
A - autonomic instability
M - memory deficits
P - Psychiatric disturbance
S - seizures
```
Dimmed - dyskinesias
117
Opsoclonus-myoclonus ataxia syndrome seen in:
Neuroblastoma (children), small cell lung cancer (adults)
118
Paraneoplastic cerebellar degeneration
| DESCRIPTION/MECHANISM & MOST COMMONLY ASSOCIATED TUMOR(S)
Antibodies against antigens in Purkinje cells.
Small cell lung cancer (anti-Hu), gynecologic and breast cancers (anti-Yo), and Hodgkin lymphoma (anti-Tr)
YO! HuTr!
119
Apocrine metaplasia of the breast...
no increased risk for cancer
120
Metastatic calcification
In normal tissues - Predominantly in interstitial tissues of:
kidney
lung
gastric mucosa
these tissues lose acid quickly; inc pH favors Ca2+ deposition)Nephrocalcinosis of collecting ducts may lead to nephrogenic diabetes insipidus and renalfailure
121
Metastatic calcification 2° to...
2° to hypercalcemia (eg, 1° hyperparathyroidism, sarcoidosis, hypervitaminosis D) or high
calcium-PHOSPHATE product levels (eg, chronic kidney disease with 2° hyperparathyroidism, long-term dialysis, calciphylaxis, multiple myeloma)
Usually abnormal
