Pathology - First Aid Flashcards
1
Q
Apoptosis requires…
A
ATP.
2
Q
Both the intrinsic and extrinsic pathways for apoptosis activate…
A
cytosolic caspases that mediate cellular breakdown.
3
Q
Unlike necrosis, apoptosis does not have…
A
significant inflammation.
4
Q
Apoptosis is charachterized by..
A
deeply eosinophilic cytoplasm, cell shrinkage, nuclear shrinkage (pyknosis) and basophilia, membrane blebbing nuclear fragmentation (karyorrhexis), and formation of apoptotic bodies, which are then phagocytosed.
5
Q
DNA laddering is a…
A
sensitive indicator of apoptosis.
6
Q
Durrying karyorrheix, endonucleases will…
A
cleave at internucleosomal regions, yielding 180-bp fragments.
7
Q
Radiation therapy causes…
A
apoptosis of tumors and surrounding tissue via free radical formation and dsDNA breakage.
8
Q
Intrinsic apoptosis pathway is invovled in..
A
tissue remodeling in embryogenesis.
9
Q
Intrinsic pathway occurs when…
A
a regulating factor is withdrawn from a proliferating cell population (ex. decreased IL-2 after a completeed immunological rxn leads to apoptosis of proliferating effector cells).
10
Q
Intrinsic pathway also occurs after exposure to…
A
injurious stimuli (radiation, toxins, hypoxia).
11
Q
During the intrinsic pathway, changes in proportions of…
A
anti- and pro- apoptotic factors lead to increased mitochondrial permeability and cytochrome c release.
12
Q
BAX and BAK are…
A
pro-apoptotic proteins.
13
Q
Bcl-2 is…
A
anti-apoptotic.
14
Q
Bcl-2 prevents…
A
cytochrome c release by binding to and inhibiting Apaf-1.
15
Q
Apaf-1 normally…
A
induces the activation of caspases.
16
Q
If Bcl-2 is overexpressed, then…
A
Apaf-1 is overly inhibitedd, leading to decreased caspase activation and tumorigenesis.
17
Q
2 pathways of the extrinsic apoptosis pathway
A
- ligand receptor interactions (FasL binding to Fas)
2. immune cell (cytotoxic T-cell release of perforin and granzyme B)
18
Q
Fas-FasL interaction is necessary in…
A
thymic medullary negative selection.
19
Q
Mutations in Fas incnresae…
A
numbers of circulating self-reacting lymphocytes due to failure of clonal deletion.
20
Q
After Fas crosslinks with FasL…
A
multiple Fas molecules coalesce forming a binding site for a death domain-containing adapter protein, FADD.
21
Q
FADD binds…
A
inactive caspases, activating them.
22
Q
Defective Fas-FasL interaction is the basis for…
A
autoimmune disorders.
23
Q
Coagulative Necrosis
A
- heart, liver, kidney
- occurs in tissues supplied by end-arteries
- increased cytoplasmic binding of acidophilic dye
- proteins denature first, followed by enzymatic degradation
24
Q
Liquefactive Necrosis
A
- brain, bacterial abscess
- occurs in CNS due to high fat content
- enzymatic degradation is due to the release of lysosomal enzymes
25
Caseous necrosis
-TB, systemic fungi, nocardia
26
Fatty necrosis
-enzymatic (pancreatitis (saponification)) and nonenzymatic (breast trauma); calcium deposits appear dark blue on staining
27
Fibrinoid necrosis
- vasculitides (Henoch-Schonlein purpura)
- Churg-Strauss
- malignant HTN
- amorphous and pink
28
Gangrenous necrosis
- dry (ischemi coagulative) and wet (infxn)
| - common in limbs and GI tract
29
Reversible cell injury (w/ O2)
1. ATP depletion
2. cellular/mitochondrial swelling
3. nuclear chromatin clumping
4. decreased glycogen
5. fatty change
6. ribosomal/polysomal detachment
7. membrane blebbing
30
Irreversible cell injury
1. nuclear pyknosis, karyorrhexis, karyolysis
2. plasma membrane damage
3. lysosomal rupture
4. mitochondrial permeability/vacuolization
31
Heart areas susceptible to ischemia/hypoxia
subendocardium (LV)
32
Kidney areas susceptible to hypoxia/ischemia
straight segment of proximal tubule (medulla)
| thick ascending limb (medulla)
33
Liver area susceptible to hypoxia/ischemia
area around central vein (zone III)
34
Colon areas susceptible to hypoxia/ischemia
splenic flexure, rectum
35
Reperfusion injury is due to...
damage by free radicals.
36
Red infarcts occur in...
loose tissues with multiple blood supplies such as liver, lungs and intestine.
37
Pale infarcts occur in...
solid tissues with a single blood supply such as heart, kidney and spleen.
38
First sign of shock is...
tachycardia.
39
Shock in the setting of DIC secondary to trauma is likely due to...
sepsis.
40
Distributive shock includes...
septic, neurogenic, and anaphylactic shock.
41
Features of Distributive shock
1. high-output failure (decreased TPR, increased CO, increased venous return)
2. decreased PCWP
3. vasodilation (warm, dry skin)
4. failure to increase blood pressure with IV fluids
42
Features of hypovolemic/cardiogenic shock
1. low-output failure (increased TPR, decreased CO, decreased venous return)
2. PCWP increased in cardiogenic; decreased in hypovolemic
3. vasoconstriction
4. blood pressure restored with IV fluids
43
Inflammation is characterized by...
redness, pain, heat, swelling and loss of function.
44
Vascular component of inflammation
increased vascular permeability, vasodilation, endothelial injury
45
Cellular component of inflammation
neutrophils extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation and inflammatory mediator release
46
Acute inflammation is mediated by...
neutrophils, eosinophils, and antibodies. There i rapid onset and it lasts minutes to days.
47
Outcomes of acute inflammation include...
complete resolution, abscess formation, and progression to chronic inflammation.
48
Chronic inflammation is mediated by...
mononuclear cell and fibroblasts. Characterized by persistent destruction and repair.
49
Chronic inflammation is associated with...
blood vessel proliferation and fibrosis.
50
A granuloma is a...
nodular collection of epithelioid macrophages and giant cells.
51
Outcomes of chronic inflammation include...
scarring and amyloidosis.
52
Chromatolysis is a process involving...
the cell body following axonal injury. Changes reflect increased protein synthesis in an effort to repair the damaged axon.
53
Chromatolysis is characterized by (3):
1. round cellular swelling
2. displacement of the nucleus to the periphery
3. dispersion of Nissl substance throughout the cytoplas
54
Dystrophic calcification is...
calcium deposition in tissues secondary to necrosis.
55
Dystrophic calcification tends to be...
localized (ex. on heart valves).
56
Dystrophic calcification is seen in...
TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, throbmi, schistosomiasis, Monckeberg arteriolosclerossi, congenital CMV + toxoplasmosis and psammoma bodies.
57
Dystrophic calcification is not directly associated with...
hypercalcemia. Patients are usually normocalcemic.
58
Metastatic calcification is..
widespread deposition of calcium in normal tissue secondary to hypercalcemia or high calcium-phosphate product. Pts are not normocalcemic.
59
In metastatic calcification, calcium deposits predominantly are in...
interstitial tissues of kidney, lungs and gastric mucosa (bc these tissues lose acid quickly; increased pH favors deposition).
60
Causes of hypercalcemia leading to metastatic calcification include...
primary hyperparathyroidism, sarcoidosis, hypervitaminosis D.
61
Causes of high calcium-phoshpate product leading to metastatic calcification include...
chronic renal failure + secondary hyperparathyroidism, long-term dialysis, calciphylaxis and warfarin.
62
4 Steps of Leukocyte Extravasation
1. Margination and rolling
2. Tight-binding
3. Diapedesis (leukocyte travels between endothelial cells and exits the blood vessels)
4. Migration (leukocyte travels through interstitium to site of injury or infection guided by chemotactic signals)
63
Step 1 Mediators
Vasculature: E-selectin, P-selectin, glyCAM-1, CD34
Leukocyte: Sialyl-Lewis, L-selectin
64
Step 2 mediators
Vasculature: ICAM-1, VCAM-1
Leukocyte: CD11/18, VLA-4 integrin
65
Step 3 mediators
Vasculature: PECAM-1
Leukocyte: PECAM-1
66
Step 4 mediators
Vasculature: C5a, IL-8, LTB4, kallikrein, PAF (chemotactic products released in response to bacteria)
67
Free radicals damage cells via...
membrane lipid peroxidation, protein modification and DNA breakage.
68
Free radical injury is initiated via...
radiation exposure, drug metabolism, redox rxns, NO, transition metals, and leukocyte oxidative burst.
69
Free radicals can be elimitated by...
enzymes (catalase, SOD, glutathione, and peroxidase)
spontaneous decay
antioxidants (Vit A, C, E)
70
Pathologies of Free Radicals include:
- retinopathy of prematurity
- bronchopumonary dysplasia
- carbon tetrachloride (leading to liver necrosis)
- acetaminophen overdose
- iron overload
- reperfusion injury
71
Inhalation injury is the most common...
pulmonary complication after exposure to fire. INhalation of the products of combustion (carbon, toxic fumes) leads to chemical tracheobronchitis, edema and pneumonia.
72
Hypertrophic scars features
- increased collagen synthesis
- parallel collagen
- confined to borders of original wounds
- infrequently recur following resection
73
Keloid scars features
- extremely increased collagen
- disorganized collagen
- extneds beyond borders of original wound
- frequently recurs following resection
74
PDGF is secreted by...
activated platelets and macrophages. It induces vascular remodeling and smooth muscle cell migration. It stimulates fibroblast growth for collagen synthesis.
75
FGF stimulates...
all aspects of angiogenesis.
76
EGF stimulates...
cell growth via tyrosine kinases
77
TGF-beta has a role in...
angiogenesis, fibrosis, cell cycle arrest.
78
Metalloproteinases have a role in...
tissue remodeling.
79
Inflammatory stage of wound healing mediators
platelets, neutrophils, macrophages
80
Characteristics of the inflammatory stage of wound healing
- clot formation
- increased vessel permeability
- neutrophil migration
- maacrophages clear debris 2 days later
81
Proliferative stage of wound healing (2-3 days later) mediators
fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages
82
Characteristics of the proliferative stage of wound healing
- deposition of granulation tissue and collagen
- angiogenesis
- epithelial cell proliferation
- dissolution of clot
- wound contraction (mediated by myofibroblasts)
83
Remodeling (1 wk later) stage of wound healing mediators
fibroblasts
84
Remodeling stage characteristics
type III collagen replaced by type I collagen; increased tensile strength of tissue
85
Granulomatous diseases
1. Bartonella henselae (cat scratch dz)
2. berylliosis
3. Churg-Strauss
4. Crohn's
5. Francisella tularensis
6. Fungal infxns
7. Granulomatosis with polyangiitis
8. Listeria
9. M. leprae
10. M. tuberculosis
11. Treponema pallidum
12. Sarcoidosis
13. Schistosomiasis
86
Granuloma formation is mediated when Th1 cells secrete...
gamma-interferon which activates macrophages. TNF-alpha from macrophages induces and maintains granuloma formation.
87
Anti-TNF drugs can cause sequestering granulomas to...
breakdown leading to disseminated disease. So you should always test for latent TB before starting anit-TNF therapy.
88
Exudate features
- cellular
- protein rich
- specific gravity > 1.02
- due to lymphatic obstruction, inflammation, infxn, malignancy
89
Transudate features
- hypocellular
- protein poor
- specific gravity < 1.012
- due to increased hydrostatic pressure (CHF), decreased oncotic pressure (cirrhosis), Na+ retention
90
Products of inflammation (fibrinogen) coat...
RBCs and cause aggregation. When aggregated, RBCs fall at a faster rate within the test tube (measure of erythrocyte sedimentation rate).
91
Conditions with increased ESR
- most anemias
- infxns
- inflammation
- cancer
- pregnancy
- autoimmune disorders
92
Conditions with decreased ESR
- sickle cell (due to altered shape)
- polycythemia (increased RBCs "dilute" aggregation factors)
- CHF
93
Mechanism of iron poisoning
cell death due to peroxidation of membrane lipids
94
Symptoms of acute iron poisoning
nausea, vomiting, gastric bleeding, lethargy
95
Symptoms of chronic iron poisoning
metabolic acidosis, scarring leading to GI obstruction
96
Treatment for iron poisoning
Chelation (IV deferoxamine, oral deferasirox) and dialysis
97
Amyloidosis is...
abnromal aggregation of proteins into beta-pleated sheet structures leading to damage and apoptosis.
98
AL amyloidosis (primary) is due to...
deposition of proteins from Ig Light chains. It can occur as a plasma cell disorder or associated with multiple myeloma.
99
AL amyloidosis often affects...
multiple organ systems including:
- renal (nephrotic sydnrome)
- cardiac (restrictive cardiomyopathy, arrhythmia)
- hematologic (easy bruising)
- GI (hepatomegaly)
- neurologic (neuropathy)
100
AA amyloidosis (secondary) is seen with...
chronic conditions such as RA, IBD, spondyloarthropathy, and protracted infxn.
101
AA amyloidosis is due to...
fibrils composed of serum Amyloid A and is often multisystem.
102
Dialysis-related amyloidosis is due to...
fibrils composed of beta2-microglobulin in pts with ESRD or on long-term dialysis. May present as carpal tunnel.
103
Heritable amyloidosis is a...
heterogenous group of disorders. Example is ATTR neurologic/cardiac amyloidosis due to transthyretin gene mutation.
104
Age-related systemic amyloidosis is due to...
deposition of normal TTR in myocardium, etc. Slower progression of cardiac dysfunction relative to AL amyloidosis.
105
Organ-specific amyloidosis is most important in...
Alzheimer disease due to deposition of amyloid-beta protein cleaved from APP.
106
Islet amyloid polypeptide (IAPP) is commonly seen in...
T2DM and is caused by deposition of amylin in pancreatic islets.
107
Lipofuscin is a...
yellow-brown "wear and tear" pigment associated with normal aging.
108
Lipofuscin is formed by...
oxidation and polymerization of autophagocytosed organellar membranes.
109
Autopsy of elderly person will reveal deposits of...
lipfuscin in the heart, liver, kidney, eye, etc.
110
Hyperplasia features
-increased number of cells
111
Dysplasia is an...
abnormal proliferation of cells with loss of size, shape and orientation.
112
Carcinoma in situ features
- neoplastic cells have not invaded basement membrane
- high N/C ratio and clumped chromatin
- neoplastic cells encompass the entire thickness
113
Invasive carcinoma features
- cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
- can metastasize if they reach a blood or lymph vessel
114
P-glycoprotein is also known as...
multidrug resistance protein 1 (MDR1).
115
P-glycoprotein is expressed by some cancer cells (colon, liver) to...
pump out toxins, including chemo agents.
116
Anaplasia is...
loss of structural differentiation and function of cells, resembling primitive cells of the same tissue. Often equated with undifferentiated malignant neoplasms.
117
Desmoplasia is...
fibrous tissue formation in response to neoplasm.
| ex. linitis plastica in diffuse stomach cancer
118
Grade is determined by...
the degree of cellular differenitation and mitotic activity.
119
More prognostic value is determined by...
stage (rather than grade).
120
Stage is the degree of...
localization/spread based on site and size of primary lesion, spread to regional LNs, and metastases.
121
The term carcinoma implies...
epithelial origin.
122
The term sarcoma implies...
mesenchymal origin.
123
Most carinomas spread...
through the lymphatics.
```
Exceptions:
RCC through renal vein.
HCC through hepatic vein.
Follicular carcinoma of thyroid
Choriocarcinoma
```
124
Most sarcomas spread...
hematogenously.
125
Cachexia is...
weight loss, muscle atrophy, and fatigue that occurs in chronic disease (cancer, AIDS, heart failure, TB).
126
Cachexia is mediated by...
TNF-alpha, IFN-gamma, and IL-6.
127
Acanthosis nigricans is ass. w/
visceral malignancy (esp. stomach).
128
Actinic keratosis is associated with...
SCC of the skin.
129
AIDS is associated with...
aggressive malignant lymphomas (non-Hodgkin) and Kaposi sarcoma.
130
Autoimmune diseases are associated with...
lymphoma.
131
Chronic atrophic gastritis, pernicious anemia and postsurgical gastric remnants are associated with...
gastric adenocarcinoma.
132
Cirrhosis is associated with...
HCC.
133
Cushing syndrome is associated with...
small cell lung cancer.
134
Dermatomyositis is associated with...
lung cancer.
135
Down Syndrome is associated with...
ALL and AML.
136
Dysplastic nevus is associated with...
malignant melanoma.
137
Hypercalcemia is associated with...
squamous cell lung cancer.
138
Immunodeficiency states are associated with...
malignant lymphomas.
139
Lambert-Eaton myasthenic syndrome is associated with...
small cell lung cancer.
140
Myasthenia gravis and pure RBC aplasia is associated with...
thymoma.
141
Paget disease of bone is associated with...
secondary osteosarcoma and fibrosarcoma.
142
Plummer-Vinson syndrome is associated with...
SCC of esophagus.
143
Polycythemia is associated with...
RCC and HCC.
144
Radiation exposure is associated with...
leukemia, sarcoma, papillary thyroid cancer and breast cancer.
145
SIADH is associated with...
small cell lung cancer.
146
Tuberous sclerosis is associated with...
giant cell astrocytoma, renal angiomyolipoma, and cardiac rhabdomyoma.
147
UC is associated with...
colonic adenocarcinoma.
148
Xeroderma pigmentosum and albinism is associated with...
melanoma, basal cell carcinoma and squamous cell carcinomas of the skin.
149
BCR-ABL
CML, ALL
| tyrosine kinase gene
150
bcl-2
follicular and undifferentiated lymphomas
| anti-apoptotic molecule gene
151
BRAF
melanoma
| serine/threonine kinase gene
152
c-kit
gastrointestinal stromal tumor
| cytokine receptor gene
153
c-myc
Burkitt lymphoma
| transcription factor
154
HER2/neu
breast, ovarian, gastric carcinomas
| tyrosine kinase gene
155
L-myc
lung tumor
| transcription factor
156
N-myc
neuroblastoma
| transcription factor gene
157
ras
colon cancer, lung cancer, pancreatic cancer
| GTPase gene
158
ret
MEN 2A and 2B
| tyrosine kinase gene
159
APC
colorectal cancer (esp. associated with FAP)
160
BRCA1 and BRCA2
breast and ovarian cancer
| DNA repair protein
161
CPD4/SMAD4
pancreatic cancer
| DPC
162
DCC
colon cancer
| DCC
163
NF1
NF1
| RAS GTPase activating protein (neurofibromin)
164
NF2
NF2
| Merlin (schwannomin) protein
165
p16
melanoma
| cyclin-dependent kinase inhibitor 2A
166
p53
most cancers; Li-Fraumeni syndrome
| transcription factor fo p21, blocks G1 to S phase
167
PTEN
breast cancer, prostate cancer, endometrial cancer
168
Rb
retinoblastoma, osteosarcoma
| inhibits EF2; blocks G1 to S phase
169
TSC1
tuberous sclerosis
| Hamartin protein
170
TSC2
tuberous sclerosis
| tuberin protein
171
VHL
von Hippel-Lindau disease
| inhibits hypoxia inducible factor 1a
172
WT1 and WT2
Wilms tumor (nephroblastoma)
173
Alkaline phosphatase is a tumor marker for...
metastases to bone, liver, Paget disease of bone, serminoma (placental ALP)
174
alpha-fetoprotein is a tumor marker for...
HCC, hepatoblastoma, yolk sac tumor, testicular cancer, mixed germ cell tumor
175
beta-hCG
hydatidiform moles, choriocarcinoma, testicular cancer
176
CA-15-3/CA-27-29
breast cancer
177
CA-19-9
pancreatic adenocarcinoma
178
CA-125
ovarian cancer
179
Calcitonin
medullary thyroid cancer
180
CEA
CarcinoEmbryonic Antigen
| very nonspecific
181
S-100
neural crest origin (melanomas, neural tumors, schwannomas, Langerhans cell histiocytosis)
182
TRAP
Tartate-Resistant Acid Phosphatase (TRAP)
| hairy cell leukemia
183
EBV associated cancers
Burkitt
Hodgkin
nasopharyngeal carcinoma
CNS lymphoma
184
HBV, HCV associated cancer
HCC
185
HHV-8 associated cancer
Kaposi sarcoma, body cavity fluid B-cell lymphoma
186
HPV associated cancer
cervical and penile/anal carcinoma, head/neck/throat cancer
187
H.pylori associated cancer
gastic adenocarcinoma and MALToma
188
HTLV-1 associated cancer
adult T-cell leukemia/lymphoma
189
Liver fluke (chlonorchis) associated cancer
cholangiocarcinoma
190
Schistosoma haematobium associated cancer
bladder cancer (squamous cell)
191
Aflatoxins cause...
HCC
192
Alkylating agents cause...
leukemia/lymphoma
193
Aromatic amines cause...
transitional cell carcinoma of the bladder
194
Arsenic causes...
angiosarcoma (liver)
lung cancer
SCC (skin)
195
Asbestos causes...
bronchogenic carcinoma > mesothelioma
196
Cigarette smoke causes...
```
Transitional cell carcinoma (bladder)
SCC/Adenocarcinoma (esophagus)
RCC
Squamous cell carcinoma (larynx)
Squamous cell and small cell carcinoma (lung)
Pancreatic adenocarcinoma
```
197
Nitrosamines (smoked food) causes..
gastric cancer.
198
Radon causes...
lung cancer.
199
Vinyl chloride causes...
angiosarcoma of the liver.
200
Hodgkin lymphoma (and some non-Hodgkins) can secrete...
calcitriol causing hypercalcemia.
201
Small cell lung carcinoma secretes...
ACTH causing cushing syndrome. And antibodies against presynaptic calcium channels at NMJ causing Lambert-Eaton myasthenic syndrome.
202
Small cell lung carcinoma and intracranial neoplasms secrete...
ADH leading to SIADH.
203
RCC, thymoma, hemangioblastoma, HCC, leiomyoma and pheochromocytoma can all secrete...
EPO leading to polycythemia.
204
Squamous cell carcinoma of the lung, RCC and breast cancer can all secrete...
PTHrP leading to hypercalcemia.
205
Psammomma bodies are...
laminated, concentric, calcific spherules.
206
Psammoma bodies are seen in (4)..
- papillary carcinoma of the thyroid
- serous papillary cystadenocarcinoma of the ovary
- meningioma
- malignant mesothelioma
