1
Q
The exception to the rule that pathologic hyperplasia can lead to dysplasia cancer.
A
BPH: benign prostatic hyperplasia
2
Q
Major cellular mechanism of cellular hypertrophy
A
Protein synthesis, gene activation and production of organelles (cytoskeleton, mitochondria)
3
Q
Permnent tissues cannot undergo hyperplasia or hypertrophy. What are the 3 examples of permanent tissue in the body?
A
Hyperplasia
- Cardiac muscle
- Skeletal muscle
- Nerve
4
Q
Classical example of pathologic hyperplasia leading to dysplasia and cancer (female)
A
Endometrial hyperplasia
5
Q
Mechanism of atrophy (2)
A
- Apoptosis (decrease number of cells)
2. Ubiqiquitin-proteasome degradation of cytoskeleton; autophagy (cell size)
6
Q
Metaplasia most often involves what body surfaces
A
Surface epithelium
7
Q
Classical example of metaplasia (GIT)
A
Barret’s esophagus (squamous–> columnar w/ goblet cells)
8
Q
What is the mechanism of metaplasia? Is it reversible?
A
Reprogramming of stem cells; yes
9
Q
What is the exception to the rule that metaplasia can progress to dysplasia and cancer (female).
A
Apocrine metaplasia (Fibrocystic change of the breast)
10
Q
Deficiency of what vitamin can lead to metaplasia, i.e. keratomalacia?
A
Vitamin A: keratomalacia
11
Q
t(15, 17) translocation
A
APML (cells trapped in blast)
* Treatment with ATRA
12
Q
Mesenchymal tissues can undergo metaplasia. The classical example is:
A
Myositis ossificans; caused by trauma
(Metaplastic production of bone in the skeletal muscle); look for ossificatiion within the skeletal muscle. This is not an osteosarcoma b/c there is distinct separation
13
Q
How do you differentiate between osteosarcoma and myositis ossificans on an X-ray?
A
OS: part of bone
MO: distinct separation of bone from muscle
14
Q
3 uses of vitamin A in the body
A
- Night blindness
- Immuno cells
- Specialized epithelium
15
Q
T/F Dysplasia is reversible
A
True
16
Q
Aplasia; classical example
A
Failure of cellular production during embryogenesis
17
Q
Hypoplasia; classical example
A
Decrease in cell production during embryogenesis
Streak ovary in Turner Syndrome
18
Q
Cell injury occurs when stress ___________
A
Exceeds a cell’s ability to adapt; type of stress, severity, type of cell affected
19
Q
Slow progressive decrease in blood supply to the kidney results in _________; whereas a rapid decrease in blood supply results in _______
A
- Atrophy
2. Infarction
20
Q
T/F Neurons are very susceptible to hypoxia.
A
True
21
Q
Common causes of cellular injury
A
Inflammation, nutritional deficiency/excess, hypoxia, trauma, genetic mutations
22
Q
Define hypoxia
A
Low oxygen delivery to tissue; low ATP; cellular injury
23
Q
The 3 major causes of hypoxia
A
- Ischemia
- Hypoxemia
- Decreased O2 carrying capacity of the blood
24
Q
Define ischemia. Through what 3 mechanisms can ischemia occur?
A
Decreased blood flow through an organ;
- Arterial flow blockage (atherosclerosis)
- venous outflow obstruction
- Shock (heart, hypovolemic, neurogenic, septic, anaphylactic)
25
What is Budd Chiari syndrome? What is the most common cause of Budd Chiari syndrome?
Thrombosis of the hepatic vein
| * Polycythemia vera (most common cause of Budd Chiari)
26
What AI disorder is associated with Budd Chiari Syndrome?
SLE; lupus anti-coagulant
27
Define hypoxemia.
Low partial pressure of O2 in the blood ( PaO2< 60; < 90%)
28
Describe the sequence of events in oxygenation of the blood.
FiO2 --> PAO2 --> PaO2 --> SaO2
FiO2: high altitude
PAO2: CO2 build up, PAO2 goes down
PaO2: i/s fibrosis lung
29
Decreased O2 carrying capacity arises with Hb loss or dysfunction. Give several examples.
1. Anemia: decrease RBC mass; PaO2 and SaO2 are normal
2. CO poisoning [binds Hb 100X > O2]
3. Methemoglobinemia
30
In CO poisoning, is PaO2 normal? Is SaO2 normal?
```
PaO2 = normal
SaO2 = decreased
```
31
Exposures to CO
Fires, exhaust from cars, gas heaters
32
The classic sign of CO poisoning clinically. The first detectable symptom of CO poisoning -- good for screening.
Sign: Cherry red appearance of the skin
Symptom: headache
33
Heme contains Fe2+ iron. Fe3+ cannot bind O2. Metheoglobinemia is seen clinically under these circumstances
Oxidant stress: sulfa drugs, nitrate drugs, newborns
34
Classic clinical finding in methemoglobinemia. Treatment is:
Chocolate-colored blood with cyanosis
| Treatment: IV methylene blue which will reduce iron back to 2+ state
35
Hypoxia impairs oxidative phosphorylation. The key consequences is that this results in...
Decreased ATP
36
Low ATP disrupts 3 key cellular functions. Name them.
1. Na-K pump [cell swelling]
2. Ca pump [high IC Ca can activate enzymes = bad]
3. Aerobic glycolysis [lactic acid can denature DNA and proteins]
37
The initial phase of cellular injury is reversible. What is the hallmark sign of reversible cell injury?
Cellular swelling; leads to loss of microvilli [like blowing up a glove], membrane blebbing [cytoskeleton pulled away from cell membrane] and swelling of RER [ribosomes pop off / decreased protein synthesis]
38
Reversible or irreversible cell injury: Loss of microvilli, membrane blebbing and swelling of RER (which leads to ribsome detachement and dereased protein synthesis)
Reversible cell injury
39
Hallmark of irreversible cell damage. The 3 membranes affected.
Cell membrane damage
1. Plasma membrane (enzyme in blood, IC Ca increases)
2. Mitochondrial membrane
3. Lysosome
40
Where is the ETC? Inner or outer mitochondrial membrane?
The inner mitochondrial membrane
41
Within the mitochondria, cyotchrome c is present. If it leaks into the cytosol, it can activate...
Apoptosis
42
Why is high IC calcium dangerous?
It is an enzyme activator
43
Morphologic hallmark of cell death is...
Loss of nucleus; occurs via pynknosis, karyorrhexis, karyolysis
44
Pynknosis
Shink of nucleus (ink dot)
45
Karyorrhexis
Nucleus breaking up into big pieces
46
Karyolysis
Nucleus pieces broken into building blocks
47
The 2 mechanisms of cell death
1. Necrosis (murder)
| 2. Apoptosis (suicide)
48
Necrosis is death of a large group of cells followed by...
Acute inflammation
49
T/F Necrosis is always pathologic
True
50
Coagulative necrosis
Necrotic tissue that remains firm; cell shape and organ structure are preserved by coagulation of cellular proteins
* Nucleus disappears; characteristic of all infarction except brain
51
What is the gross shape of a coagulative necrotic tissue?
Wedge-shaped and pale infarct; wedge points to the occlusion
52
What is red infarction?
Blood re-enters a loosely organized tissue. Classic example: testicle.
53
Liquefactive necrosis (3 examples)
Enzymatic lysis of cells and proteins
* Brain (microglial with hydrolytic enzymes), abscess (neutrophils with hydrolytic enzymes), pancreatitis (surrounding = fat necrosis)
54
Why do we see liquefactive necrosis in the brain?
Because the microglial cells have hydrolytic enzymes.
55
Gangrenous necrosis is...
Coagulative necrosis (ischemia of lower limb)
* Wet gangrene: superimposed infection (Liquefactive)
* Dry gangrene: mummified tissue
56
Caseous necrosis
Soft, friable necrotic tissue with cottage cheese like appearance. Combination of C & L necrosis; TB/fungal infection (granulomatous)
57
Fat necrosis (2 classic examples)
Chalky white appearance (chalky white appearance due to deposition of calcium); peripancreatic fat & trauma to the breast [giant cells, fat and calcification / can present as a mass]
58
Saponification
Fatty acids released by trauma or lipase join with calcium = dystrophic calcification
59
Dystrophic calcification
Calcium deposition on dead/dying tissue (serum Ca and PO4 normal); psammoma bodies (tumor cells outgrow blood supply)
60
Metastatic calcification
Serum Ca or PO4 elevated and has ability to force Ca into tissue and can precipitate
61
Fibrinoid necrosis. 2 examples
Necrotic damage to BV wall; leaking of proteins into blood vessel wall; results in bright pink staining. Characteristic of malignant hypertension or vasculitis.
62
In what circumstance would a 30 year old woman present with fibrinoid necrosis?
Pre-eclampsia (3rd trimester)
| * Fibrinoid necrosis of the placental blood vessels
63
T/F Apoptosis is energy-dependent, genetically programmed cell death. Three classical examples.
True
| Ex./ endometrium, embryogenesis (syndactly), killing of virally infected cells by CD8 T cells
64
Apoptotic bodies that fall from cells are removed by...
Macrophages
65
Apoptosis is mediated by caspases. These caspases activate 2 enzymes
1. Protease (break down cytoskeleton)
| 2. Endonucleases (break down DNA)
66
The 3 pathways by which caspases are activated.
1. Intrinsic mitochondrial (cellular injury, DNA damage, decreased hormonal stimulation) --> cytochrome c leaks and activates caspases
2. Extrinsic receptor-lignad (FAS --> CD95 or death receptor) -- TNF-TNFR [best example/ NEGATIVE SELECTION of T cells]
3. CD8 T-cell pathyway (MHCI --> perforins; granzyme enters pores and activates caspases)
67
BCL-2's role
Stabilize the mitochondrial membrane so that cytochrome c does not leak out
68
Oxygen with 1 e, 2 e, 3 e, 4 e. Which is the most damaging?
1. Superoxide
2. Peroxide
3. Hydroxide (Most damaging)
4. Water
69
Pathologic generation of free radicals
Ionizing radiation (OH), inflammation (PMN's O2 dept mechanism with burst -- NADPH oxidase), metals (copper and iron), drugs (acetaminophen, carbon tetrachloride)
70
What enzyme converts oxygen into superoxide in the respiratory burst?
NADPH oxidase
71
H2O2 is converted by ________ to water.
Myeloperoxidase
72
The fentin reaction generates...
The hydroxyl free radical
73
Underlying mechanism of damage in hemochromatosis or Wilson's disease?
Tissue damage 2/2 free radical damage
74
Free radicals cause this type of damage to a cell
1. Lipid peroxidation (membrane)
| 2. Oxidize DNA and proteins (oncogenesis)
75
Elimination of free radicals (3 mechanisms)
1. Antioxidants (Vitamin A, C, E)
2. Enzymes (SOD, glutathione peroxidase, catalase)
3. Metal carrier proteins (Cu/cerruloplasmin and Fe/transferrin+ferritin)
76
Name each enzyme responsible for detoxifying: superoxide, hydrogen peroxide, hydroxyl radical?
1. SO dismutase
2. Catalase
3. Glutathione peroxidase
77
Describe free radical injury: CCl4 [dry cleaning] and reperfusion injury
CCl4 --> CCl3 [P450] damages hepatocytes & fatty liver (inability to synthesize apolipoproteins that excrete fat)
* Re-perfusion injury: blood returns with oxygen and PMN's leads to continued injury
78
Misfolded protein that deposits in EC space, often around blood vessels. What is this protein called?
Amyloid
79
Congo red stain with apple-green birefringence under polarized light.
Amyloid
80
Systemic amyloidosis: primary and secondary
Primary: AL (derived from Ig light chain); associated with plasma cell dyscrasia
Secondary: AA (derived from SAA protein -- an acute phase reactant); chronic inflammatory states; malignancy; Familial Mediterranean fever
81
Familial Mediterranean fever
AR dysfunction of neutrophils; high SAA acute phase reactant during acute attacks deposits as AA amyloid; presents with episodes of fever and acute serosal inflammation (MI, appendicitis)
82
Amyloid classical clinical findings
Kidney = #1: nephrotic syndrome
- Restrictive CM/arrhythmia
- Tongue enlargement, malabsorption, HSM
83
Senile cardiac amyloidosis; what type of amyloid? Symptomatic?
ASYMPTOMATIC (25% patients > 80 years old); Non-mutated serum transthyretin deposits in the heart
84
Familial amyloid cardiomypoathy
Mutated serum transthyretin (5% AA) --> restrictive cardiomyopathy
85
DM2 amyloidosis
Amylin --> pancreas islets (derived from insulin)
86
Alzheimer's amyloid plaques made up of
B-myloid precursor protein (a-beta); Chromosome 21 [Down's Syndrome]
87
Dialysis associated amyloidosis; what type of amyloid?
Beta-2 microglobulin [component of Ig] deposits in joints; Builds up in blood
88
MTC amyloidosis
C-cell tumor (calcitonin)
89
An abscess will have this form of necrosis
Liquefactive
90
Progeria results from a defect in this protein
Lamin
91
Wermer syndrome is similar to Progeria, but patients live into their 50's. The protein defect in these patients is:
Helicase
92
Lipofuscin deposition in aging cells is 2/2
Peroxidation of membrane liquids
93
What type of cells have the greatest amount of telomerase activity?
Germ cells
94
T/F Metastatic calcification can result from ESRD.
True
95
T/F During pregnancy, the myometrium undergoes smooth muscle hypertrophy
True
96
Mallory body vs. Councilman body
Mallory body: Intracytoplasmic intermediate filaments within hepatocytes
Councilman body: Extracytoplasmic; apoptosis of a hepatocyte
97
Define inflammation
Allow PMN's & Lymphocytes & proteins into tissue space in response to infection
98
Acute inflammation is characterized by: (2 things)
Edema and PMN's
99
Acute inflammation arises in response to (2 events)
Infection or tissue necrosis
100
Examples of innate responses
Epithelium, mucus, complement, mast cells, macrophages, neutrophils, eosinophils, basophils
101
Acute inflammation is mediated by several factors.
1. TLR's
102
TLR's are present on macrophages and dendritic cells. They recognize ____________.
PAMPS (pathogen associated molecular patterns)
103
CD__ is present on macrophages and recognizes LPS on outer membrane of GN bacteria
CD14
104
TLR activation results in upregulation of: _______
NF-kappa B; molecular on-switch which turns on acute inflammatory response
105
Arachidonic acid is released from the cell membrane by....
PLA2
106
PGI, D, E mediate vasodilation and increased vascular permeability. Where along the blood vessels do these events occur?
Vasodilation (arteriole) increased vascular permeability (post-capillary venule)
107
PGE2 mediates...
Feeeeever and pain
108
LTB4
Attracts and activates PMN's
109
LTC, D, E
Mediate vasoconstriction, broncospasm, increased vascular permeability
110
4 key mediators influencing neutrophil chemotaxis
LTB4, C5a, IL-8, bacterial products
111
What is a pericyte?
Contains contractile elements underneath endothelial cells. Think leukotrienes.
112
Where are mast cells? How are they activated (3 methods)?
C/T
1. Tissue trauma
2. C3a, C5a
3. Cross-linking IgE by antigen
113
Histamine granules mediate (2 functions)
Vasodilation, increased vascular permeability
114
The delayed response of acute inflammation involves...
Leukotrienes (AA metabolites)
115
Classical complement
C1 to IgG or IgM bound to Ag
116
Alternative complemenet
Microbial products directly activate complement
117
Mannose-binding lectin pathway
MBL binds mannose on microorganisms and activates complement
118
Result of activation of complement
C3 --> C5 convertase --> MAC
119
C3a & C5a
C5a
C3b
MAC
C3a & C5a: Mast cell degran
C5a: chemotactic for neutrophils
C3b: opsonin
MAC: lyses microbes by creating holes in cell membrane
120
Hageman factor (Factor 12)
Activated upon exposure to subendothelial or tissue collagen; also activated in DIC
121
Hageman factor activates (3)
1. Coagulation
2. Complement
3. Cleaves HMWK to bradykinin [similar to histamine + pain]
122
2 molecular mediators of pain
PGE2 [feeever/pain] & Bradykinin
123
Cardinal signs of inflammation and pathophysiology
1. Red: vasodilation [histamine, PG, bradykinin]
2. Pain: bradykinin and PGE2 -- sensitize
3. Swelling: vascular permeability (histamine, tissue damage)
4. Warmth: vasodilation
5. Fever: IL-1, TNF (macrophages) --> COX/hypothalamus (PGEEE2)
124
Describe the molecular basis of fever
Pyrogens --> Macrophages (IL-1, TNF) --> COX/hypothalamus --> PGE2 increases temperature
125
The 3 phases of acute inflammation.
1. Fluid/Edema
2. PMN (24 hours)
3. Macrophage (2-3 days)
126
What is the first step of neutrophil arrival? Second step? Step 3? Step 4?
1. Margination [vasodilation slows blood flow in post capillary venules]
2. Rolling: cells slow down with selectin speed bumps
3. Adhesion
4. Transmigration
127
P-selectin is upregulated by
Weibel-Palade bodies on endothelial cells [W = VWF; P = P-selectin](mediated by histamine)
128
E-selectin is induced by
E-selectin: TNF, IL-1
129
Selectins bind to __________ on leukocytes
Sialyl Lewis X
130
Cellular adhesion occurs with CAMS which bind to ________ on neutrophils
Integrins (C5a, LTB4 upregulate)
131
Leukocyte Adhesion Deficiency
* Defect
* Mode of inheritance
* Classical clinical findings
AR recessive defect of integrins (CD18 subunit)
| * Delayed separation of umbilical cord; increased PMN's; recurrent bacterial infections that lack pus
132
What is pus?
Dead neutrophils sitting in fluid
133
Phagocytosis is enhanced by opsonins... (2)
IgG, C3b
134
Chediak-Higashi Syndrome defect and inheritance
AR protein trafficking defect; phagosome --> lysosome (RR system of MT are defective)
135
Chediak-Higashi Syndrome clinical features
Increased risk of pyogenic infections, neutropenia, giant granules in leukocytes, defective primary hemostasis, albinism, peripheral neuropathy
136
What are the 2 ways in which phagocytosed material is killed? Which is more effective?
1. O2-dependent [more effective]; HOCl plays key role
| 2. O2-independent
137
Oxygen is converted to superoxide by:
NADPH oxidase
138
Superoxide is converted to H2O2 by:
Superoxide dismutase
139
H2O2 is converted to HOCL by:
MPO
140
CGD results in poor oxygen dependent killing 2/2
NADPH oxidase defect (XLR or AR)
141
CGD patients are most susceptible to infections by catalase positive organisms such as
S. aureus, Nocardia, Aspergillus, **Pseudomas cepacia**, S. marcessens; no longer have any source of H2O2 (could be salavaged from bacteria)
142
How do you screen for CGD?
Nitroblue tetrazolium test. Turns blue = NADPH oxidase in tact. Can you convert oxygen to superoxide?
143
Defective MPO results in an increased risk for what type of infection?
Candida [usually asymptomatic]; normal NBT test
144
O2 independent killing occurs via...
Enzymes present in 2ndary granules of leukocyte (lysozyme and MBP)
145
How do neutrophils die within tissue?
Apoptosis
146
How is acute inflammation resolved?
* Resolution & healing (IL-10 and TGF-beta)
* Continued acute inflammation (IL-8)
* Abscess
* Chronic inflammation
147
Which 2 cytokines shut down the acute inflammatory process?
IL-10 & TGF-beta
148
Chronic inflammation stimuli
Persistent infection, AI disease, foreign material, cancer
149
Activation of T cells requires 2 signals
1. Binding of Ag/MHC
| 2. Second signal [B7 on APC binds to CD28 on CD4 T cell]
150
The second signal in activation of a CD4+ T cell
1. EC Ag phagocytosed and presented via MHC2 (APC)
| 2. B7 (APC) on CD28 on CD4 T cell
151
Describe the B7/CD28 interaction
B7 on APC binds to CD28 on the CD4+ T cell
152
The 2 subsets of cytokines secreted by CD4+ T Cells
1. TH1: CD8: IL2 (T cell growth factor), IFN-gamma (macrophages
2. TH2: B-cells
IL-4 (IgG/IgE class switching, 5, 10 (inhibits TH1)
153
Class switching cytokine
IL-4
154
Role of IL-5
Eosinophil chemotaxis and activation; maturation of B cells to plasma cells and class switching to IgA
155
IL-10
Inhibits Th1 cells
156
CD8+ T cells are activated by intra/extracellular Ag
Intracellular Ag
157
CD8 T cells kill targets with
Perforins, granzyme (induces apoptosis)
* Activates caspase
* Expression of FASL which binds FAS (activates apoptosis)
158
Naive B cells express surface (2 Ig's)
IgM and IgD
159
How are B cells activated? 2 ways
1. Ag--> surface IgM
| 2. B-cell to MHC 2 CD4/ CD40/CD40L
160
Granulomatous inflammation: the defining feature
Subtype of chronic inflammation: key cell = epitheloid histiocyte [macrophage with abundant pink cytoplasm]; surrounded by giant cells and rim of lymphocytes
161
Non-caseating granulomas lack _______________. Several examples of NC granulomas.
Central necrosis:
1. Reaction to foreign material (implant)
2. Sarcoid
3. Beryllium exposure
4. Crohn's disease
5. Cat Scratch disease
162
A stellate shaped non-caseating granuloma is caused by... (think ID)
Cat scratch disease
163
The DDx (2) for a caseating granuloma.
TB (AFB) or Fungal (Silver/GMS)
164
How are granulomas formed? 3 steps (name the major cytokines)
1. Macrophage:CD4+ interaction
2. IL-12/TH1 --> IFN-gamma [occurs in both caseating and non-caseating granulomas]
3. Macrophage to epitheloid histiocyte
165
DiGeorge Syndrome is a developmental failure of ____________ due to ____________
3rd and 4th pharyngeal pouches 2/2 22q11 microdeletion
166
DiGeorge Syndrome p/w
T-cell deficiency (lack of thymus); hypocalcemia (PTH); abnormal heart, great vessels, face
167
SCID results from defective:
Cell mediated and humoral immunity
168
Etiologies of SCID include (3)
1. Cytokine receptor defects
* 2. ADA deficiency *
3. MCH Class 2 deficiency
169
Treatment of SCID
Isolation & stem cell transplant
170
X-linked agammaglobulinemia
| * Most common mutation
Complete lack of Ig 2/2 disordered B-cell maturation
| * Bruton tyrosine kinase signalling molecule
171
X-linked agammaglobulinemia p/w
Bacterial, enterovirus (IgA/mucosal surfaces), and Giardia infections after 6 months of life; live vaccines must be avoided
172
Common variable immunodeficiency due to:
Patients p/w
Patients at increased risk for
B-cell or T-helper cell defect
* Bacteria, enterovirus, Giardia
* Present late childhood
* AI + Lymphoma
173
IgA deficiency is the most common Ig deficiency; increased risk of...
Mucosal/viral infections
174
Which GI disease is associated with IgA deficiency?
Celiac disease
175
Hyper-IgM syndrome is due to...
```
Mutated CD40L or CD40 Receptor; second signal cannot be delivered to helper T-cells during B-cell activation
* Cytokines necessary for Ig class switching are not produced; recurred pyogenic infections, especially at mucosal sites (IgA, IgG, IgE)
```
176
Wiskott-Aldrich Syndrome triad
TBOpenia, Eczema, Recurrent infections (humoral and cell-mediated)
177
Wiskott-Aldrich Syndrome inheritance and gene defect
X-linked WASP gene
178
C5-C9 deficiency increased risk for
Neisseria infection
179
C1 esterase inhibitor deficiency results in
Hereditary angioedema characterized by periorbital edema
180
The underlying principle of AI disorders
Loss of self-tolerance
181
Autoimmune polyendocrine syndrome triad
```
* Central tolerance goes awry
AIRE mutation in the medullary epithelial cells in the thymus
1. Hypoparathyroidism
2. Adrenal failure
3. Candida
```
182
Positive selection; negative selection in the thymus. What part of the thymus does each occur?
Positive (Cortex): must recognize MHC and self-Ag
| Negative (Medulla): bind self-Ag [dendritic cells and medullary epithelial cells]
183
Central tolerance in the bone marrow
1. Receptor editing of light chain (RAG genes reexpressed)
| 2. Apoptosis
184
If central tolerance fails, the lymphocyte can still undergo negative selection in the periphery. How does this occur?
The second CD28/B7 signal does not occur. The CD4 T cell can undergo anergy or apoptosis.
185
CD95
FAS receptor (binds FAS Ligand) induces apoptosis
186
Autoimmune lymphoproliferative syndrome (ALPS)
* Loss of peripheral tolerance
| Mutations in the FAS apoptosis pathway. [FAS, FAS-L, caspase-10]
187
Tregs suppress immune responses in 2 ways.
1. Block CD4+ cells (CTLA-4 on T-reg blocks B7)
| 2. Cytokines: IL-10 (limits MHC 2 and co-stimulator molecules), TGF-beta (inhibits macrophages)
188
The 3 types of Tregs.
1. CD4+
2. CD25+ (IL-2 Receptor)
3. FOXP3 (Transcription factor)
189
CD25 polymorphisms are assoicated with which AI conditions?
MS, DM1 [Tregs]
190
FOXP3 mutations result in...
IPEX (Immune polyendocrineopathy, X-linked)
| * Islets, DM1, diarrhea
191
Why do AI conditions occur in women of child bearing age?
Estrogen reduces apoptosis of self-reactive B-cells.
192
PTPN22 gene polymorphisms can result in...
Loss of self tolerance
Tyrosine phosphatase --> signalling mechanisms go awry and AI develops
193
SLE summary (Type 3 Hypersensitivity)
Decreased CH50, C3, C4
| * Ab directed against host nuclear material and the complexes deposit in tissues, activating complement
194
Early complement deficiency (particularly C2) is associated with..
SLE b/c you need the early complement components to initiate the immune complex clearing process
195
Aside from a malar rash upon exposure to sunlight, SLE patients can present with this type of rash.
Discoid rash
196
The pancytopenia seen in SLE patients is a T2 or T3 hypersensitivity reaction?
T2
197
In Libman-Sacks endocarditis, vegetations on valves are on one or both sides of valves.
Both sides of valves
198
The 3 anti-phospholipid antibodies that are commonly tested clinically with SLE:
1. Anticardiolipin (VDRL/RPR)
2. Lupus anticoagulant (falsely elevated PTT b/c interferes with the test)
3. Anti-beta-2-glycoprotein I
199
Antiphospholipid Ab syndrome [associated with SLE, but more commonly not associated with SLE]
Antiphospholipid Ab + hypercoagulable state; Arterial and venous thrombosis
200
The 3 classic drugs associated with anti-histone Ab+ SLE
1. Hydralazine
2. Procainamide
3. INH
201
Most common causes of death in SLE (2).
Renal failure (MN or DPGN) and infection
202
T/F SLE patients have accelerated coronary atherosclerosis.
True
203
Sjogren's syndrome: what type hypersensitivity reaction?
Type 4: AI destruction salivary and lacrimal glands (dry eyes, dry mouth, dental caries)
204
The most common AI condition associated with Sjogren's syndrome
RA (can have RF in blood)
205
Anti-ribonucleoprotein Ab
Anti-SSA and Anti-SSB
Sjogren's syndrome
* associated with extragrandular manifestations
* Risk of neonatal lupus and congenital heart block
206
Anti-SSA and neonates
Neonatal lupus and congenital heart block
207
Lymphocytic sialadenitis
Sjogren's syndrome
| Important to biopsy to R/O sarcoidosis, amyloidosis
208
Sjogren's syndrome have an increased risk for...
B-cell lymphoma (presents as unilateral enlargement of parotid late in disease course)
209
Systemic sclerosis (Scleroderma)
AI damage of mesenchyme leads to fibroblast proliferation and collagen deposition
* Endothelin, PDGF, TGF-B
210
CREST syndrome
```
Calcinosis (Anti-centromere Ab)
Raynaud
Esophageal dysmotility
Sclerodactyly
Telangiectasias of skin
```
211
DNA topoisomerase I Ab
Scleroderma
212
Most common cause of death in scleroderma
Lungs
213
Mixed connective tissue disease (name the Ab)
SLE, SS, polymyositis
| ANA with serum Ab against U1 RNP
214
ANA with Anti-U1 RNP Ab
Mixed connective tissue disease
215
T/F Healing occurs via a combination of regeneration and repair.
True
216
Labile tissues continually regenerate. Give several examples and name where the stem cell layers are.
Bowl (crypts), skin (basal layer), bone marrow
217
CD34
Marker of hematopoietic stem cell
218
What is the marker of the hematopoetic stem cell?
CD34
219
What is the stem cell of the lung?
Type 2 pneumocyte
220
Stable tissues are quiescent, but can re-enter the cell cycle. Classic example is. Give a second example in the kidney.
Liver: compensatory hyperplasia 2/2 partial resection.
| * Also PCT of kidney
221
Permanent tissues lack significant regenerative potential. The 3 examples:
Skeletal muscle, cardiac muscle, neurons
222
Repair replaces damaged tissue with a...
Fibrous scar
223
Why do scars appear on the skin?
Regenerative stem cells of the skin can be lost with a deep laceration
224
Granulation tissue consists of (3 components)
1. Fibroblasts (collagen 3)
2. Capillaries (nutrients)
3. Myofibroblasts (contracts wound)
225
Eventually, collagen 3 is replaced with collagen type ___. What converts collagen 3? What is the co-factor?
1
| Collagenase removes collagen 3 and requires Zn
226
Collagen 1
Bone
| * Tensile strength
227
Collagen 2
Cartilage
228
Collagen 3
Pliable: BV (stretch), granulation tissue, embryonic tissue (stretch)
229
Collagen 4
Basement membrane
230
```
These factors are important in repair/healing. State their purpose.
TGF-alpha
TGF-beta
PDGF
FGF
VEGF
```
```
TGF-alpha: epithelial, fibroblast
TGF-beta: FGF, inhibit inflammation
PDGF: endothelium, smooth muscle, FGF
* FGF: angiogenesis *; skeletal development
VEGF: angiogenesis
```
231
Healthing by primary intention
Wound edges sutured together (minimal scar)
232
Healing by secondary intention
Edges are not approximated; granulation tissue fills in the defect (big scar & contraction of wound by myofibroblasts)
233
Delayed wound healing causes (think biochemistry)
Infection (most common cause)
Vitamin C [hydroxylation proline, lysine] , Cu [lysyl oxidase], Zn (collagen 3-->1)
* foreign body, ischemia, DM, malnutrition
234
GLY-Proline-Lysine gets hydroxylated in collagen by what cofactor? Why is this necessary?
Vitamin C; necessary for cross-linking
235
Dehiscence
Rupture of wound; most commonly seen in abdominal surgery
236
Hypertrophic scar vs. Keloid
Hypertrophic: collagen 1 in a wound
Keloid: Excess collagen 3 outside of wound & way out of proportion (ear-lobe classic location)
237
How can you determine clonality of cancer cells? What about B cells?
G6PD isoforms (G6PD on X chromosome); Androgen receptor isotypes; Ig light chain [kappa: lambda 3:1]
238
What is the normal ratio of kappa:lambda in a B cell?
3:1
239
The 3 DDX for LAD.
1. Infection (reactive hyperplasia)
2. Lymphoma
3. Metastatic cancer
240
Are benign tumors monoclonal?
Yes
241
```
Name the tumors (benign + malignant)
Epithelium
Mesenchyme
Lymphocyte
Melanocyte
```
Adenoma/Adenocarcinoma
Lipoma/Liposarcoma
( ) Lymphoma/Leukemia
Nevus/Melanoma
242
Causes of death in adults (3 major) & in children (3)
1. Cardiovascular disease
2. Cancer
3. Cerebrovascular
- --
1. Accidents
2. Cancer
3. Congenital defects
243
Most common cancers in adults (incidence): 3
1. Breast/prostate
2. Lung
3. Colorectal
244
Most common cancers in adults (mortality): 3
1. Lung
2. Breast/prostate
3. Colorectal
245
Approximately how many cancer divisions occur before the earliest clinical symptoms arise?
30
246
T/F Each cancer division results in increased mutations. Cancers that do not produce symptoms until late will have undergone additional divisions and mutations. Cancers detected late have a poor prognosis
True
247
The 2 major goals of cancer screening.
1. Catch dysplasia before it becomes carcnioma
| 2. Detect carcinoma before clinical symptoms arise
248
Tumor is driven by:
DNA mutations
249
Cancer: Aflatoxins
HCC
250
Cancer: Alkylating agents
L/L
251
Cancer: Alcohol
SCC OP, upper esophagus, pancreatic, HCC
252
Cancer: Aresnic
SCC skin, lung cancer, angiosarcoma liver
253
Cancer: Asbestos
Lung cancer; mesothelioma
254
Cancer: Cigarette smoke
OP cancer, esophagus, lung, kidney, bladder
255
Cancer: Nitrosamines
Stomach carcinoma
256
Cancer: Napthylamine
Urothelial carcinoma of bladder
257
Cancer: Vinyl chloride (PVC pipes)
Angiosarcoma of the liver
258
Cancer: Nickel, Chromium, Beryllium, Silica
Lung carcinoma
259
Cancer: EBV
NP carcinoma [Chinese, African], BL, CNS lymphoma (AIDS)
260
Cancer: HHV-8
KS [endothelial cells]
261
Cancer: HBV, HCV
HCC
262
Cancer: HTLV-1
Adult T-cell leukemia, lymphoma
263
Cancer: HPV 16, 18, 31, 33
SCC vulva, vagina, anus, cervix (AC cervix)
264
Cancer: ionizing radiation [nuclear reactor]
AML, CML, Papillary carcinoma of the thyroid [hydroxyl free radicals]
265
Cancer: nonionizing radiation (UVB)
Basal cell carcinoma, SCC, melanoma [pyrimidine dimers in DNA, normally excised by restriction endonuclease]
266
3 key regulatory systems disrupted in cancer
1. Proto-oncogenes
2. Tumor suppressor genes
3. Regulators of apoptosis
267
Mutations of proto-oncogenes form...
Oncogene: unregulated cell growth
268
4 categories of oncogenes
1. Growth factors (PDGF)
2. Growth factor receptors (EGFR, RET, KIT)
3. Signal transducers (RAS, ABL)
4. Cell cycle (CDK) and nuclear regulators (MYC)
269
Cancer associated with PDGF-B mutation
Platelet dervied growth factor: Astrocytoma
270
Cancer associated with EGFR (Her2Neu) amplification
Breast cancer
271
Cancer associated with RET point mutation
MEN 2A, 2B [sporadic MTC]
272
Cancer associated with KIT point mutation
GIST
273
Cancer associated with RAS gene family
Carcinomas, melanoma, lymphoma (GTP binding protein -- inability to cleave RAS GTP to make RAS GDP)
274
Cancer associated with ABL
t(9, 22) with BCR-ABL [CML and some forms of ALL]
275
Cancer associated with c-MYC TF
Burkitt's Lymphoma t(14,18)
276
Cancer associated with N-MYC TF
Neuroblastoma
277
Cancer associated with L-MYC TF
SCLC
278
Cancer associated with cyclin D1
t(11,14) Mantle cell lymphoma
| G1-S phase transition
279
RAS in OFF state = (GDP or GTP)
RAS-GDP
280
RAS in ON state = (GDP or GTP)
RAD-GTP
281
Cancer associated with CDK4
Melanoma
282
Histologic features of Burkitt's lymphoma
Starry sky appearance
283
In a lymph node, the 3 areas of B cells include (think lymphoma)
Follicle, Mantle, Margin
284
The 2 major tumor supressor genes
p53, Rb
285
p53 regulates which transition in the cell cycle?
G1-S phase transition
286
BAX
Destroys BCL-2; allows cytochrome C to leak out of mitochondria and cause apoptosis (p53 allows)
287
Germline mutation in p53 results in what syndrome?
LiFraumeni syndrome: increased risk for multiple types of carcinomas and sarcomas
288
Rb regulates which transition in the cell cycle
G1-S phase
289
T/F Phosphorylated Rb is happy. It then releases E2F, which allows G1-S transition.
True
290
Who phosphorylates Rb?
Cyclin D
291
T/F A mutated Rb results in constitutively free E2F
True
292
Sporadic vs. Germline mutation of Rb; unilateral/bilateral
Sporadic: unilateral
Germline: B/L & osteosarcoma
293
BCL2 overespression occurs in what cancer?
Follicular lymphoma (t(14,18))
294
Telomerase is a necessary enzyme for cell immortality. Normally telomeres shorten and results in cellular senescence. Cancers have up/downregulated telomerase
Upregulated
295
T/F Angiogenesis is necessary for tumor growth survival
True
296
Why does immunodeficiency increase risk for cancer?
Downregulated MHC1 allows for evasion of immune surveillance
297
T/F Downregulation of e-cadherin can result in cancer spread. What are the next steps?
True
2. Lamin (basement membrane)
3. Collagenase 4
4. Fibronectin
298
Which carcinomas spread via the blood?
RCC, HCC, choriocarcinoma, Follicular carcinoma thyroid
299
Omental caking is characteristic of
Ovarian carcinoma
300
T/F Immunohistochemistry is used to characterize different tumors.
True
301
Intermeidate filament immunohistochemical stain: Keratin
Epithelium
302
Intermediate filament immunohistochemical stain: Vimentin
Mesenchyme
303
Intermediate filament immunohistochemical stain: Desmin
Muscle
304
Intermediate filament immunohistochemical stain: GFAP
Neuroglia
305
Intermediate filament immunohistochemical stain: neurofilament
Neurons
306
Immunohistochemical stain: S-100
Melanoma
307
Immunohistochemical stain: Chromogranin [Differentiate between the best and worse differentiated types of this tumor]
Neuroendocrine cells
Best: Carcinoid
Worst: SCLC
308
Grading cancer takes into account the extent of
Differentiation
309
Staging cancer takes into account
Tumor size
Mets
Nodes
310
Paget's disease of the breast indicates an underlying
Ductal carcinoma
311
Hemangioblastoma of retina, cerebellum, medulla with bilateral RCC
Von Hippel Lindau syndrome (Ch. 3)
312
Astrocytoma, Retinal Hamartoma, Hypopigmented spots and seizures
Tuberous sclerosis
313
Perivascular Homer-Wright Rosettes
Medulloblastoma
314
Pancoast tumor: SCC vs. Adenocarcinoma
SCC
315
Cafe au lait spots, Lisch nodule with a yellow-brown iris (Chromosome 17)
NF-1
316
B/L CN8 neuroma, juvenile cataracts (Chromosome 22)
NF-2
317
Port-wine stain with CN6 palsy
Sturge-Weber Syndrome
318
Colorectal & brain tumor
Turcot's Syndrome
319
Colorectal polyposis and osteoma
Gardner's syndrome
320
Microcephaly, micrognathia, polydactly, hypotonia
Patau Syndrome (Ch. 13)
321
Chromosome of Cri-du-Chat
5
322
Ank protein (ID)
Legionella
323
Thickened hyperpigmented skin with velvety texture
Basal cell carcinoma
324
Stable angina results in reversible/irreversible injury to myocytes?
Chest pain with exertion; reversible injury to myocytes
325
Stenosis at what % results in angina?
70%
326
Stable angina shows what on EKG?
ST depression
327
Which region of the heart muscle is most susceptible to ischemic damage?
Epi, Myo *** Endo
| [Subendocardium]
328
The hallmark of subendocardial ischemia on EKG
ST-depression
329
Unstable angina results from...
Rupture of plaque: exposure of sub-endothelial collagen; partial occulusion
330
EKG findings unstable angina
ST-depression
331
Prinzmetal angina 2/2
Vasospasm of coronary artery
332
EKG findings Prinzmetal angina
ST-elevation [epicardium BV clamping down]
333
MI is 2/2
Necrosis of cardiac myocytes [rupture of plaque with TBX and complete occlusion]. Also due to vasospasm, emboli and vasculitis
334
The most common artery involved in an MI
LAD: anterior wall and anterior interventricular septum
335
The most sensitive cardiac enzyme marker for an MI
Troponin I [up for 7-10 days]
336
Why is CK-MB useful as a cardiac enzyme?
Detects reinfarction days after an MI; rises 6 hours after infarction, peaks at 24, normal by 3 days
337
Treatment of MI
ASA/heparin, O2, nitrates, beta-blocker, ACEi
338
Following an MI, fibrinolyis or angioplasty can cause... (2)
1. Contraction band necrosis (Calcium returns to dead tissue)
2. Reperfusion injury (free radicals); cardiac enzymes continue to rise
339
```
MI microscopic changes
< 4 hours
4-24 hours
1-3 days
4-7 days
1-3 weeks
1 month
```
```
< 4 hours: none
4-24 hours: coag nex [dark discoloration]
1-3 days: PMN [yellow]
4-7 days: Macrophages [yellow]
1-3 weeks: Granulation
```
1 day: Coag nex
---pmns---
1 week: Macrophages
1 month: Scar
340
Key complication < 4 hours following an MI
Cardiogenic shock, CHF, arrhythmia
341
Key complication 4-24 hours following an MI
Arrhythmia
342
Key complication 1-3 days following MI
Fibrinous pericarditis (transmural infarction)
343
Key complication 4-7 days following MI
Rupture (cardiac tamponade, shunting, papillary muscle -- MR)
344
The papillary muscle of the heart is fed by what artery?
RCA
345
3 major complications following a healed MI [6-8 weeks following an MI]
1. Aneurysm
2. Thrombus
3. Dressler syndrome (anti-pericardium Ab)
346
```
Macroscopic changes following an MI
< 4 hours
4-24 hours
1-3 days
4-7 days
1-3 weeks
4+ weeks
```
```
< 4 hours: none
4-24 hours: dark discoloration
Through 1 week: yellow
1-3 weeks: red band (granulation)
>4 weeks: white scar
```
347
Can you see fibrinous pericarditis with a subendocardial infarction?
No; only with a transmural infarction
348
90% of patients who present with sudden cardiac death have pre-existing
```
Severe atherosclerosis (MVP, CM, cocaine)
* Due to sudden ventricular arrhythmia
```
349
L-sided CHF etiology
Ischemia, HTN, dilated CM, MI, restrictive CM
350
What are heart failure cells?
Hemosiderin-iron laden macrophages seen in the lung
351
The mainstay treatment of CHF
ACEi
352
What is the underlying pathophysiology of cor pulmonale?
Hypoxic vasoconstriction leads to an overworked RV
353
Nutmeg liver
RHF
354
Most common congenital heart defect. Associated with FAS
VSD
355
Eisenmenger syndrome
Reversal of a L-R congenital shunt: RVH, polycythemia, clubbing
356
Most common type of ASD. Which one is associated with Down's Syndrome?
Ostium secundum
| * Ostium primum
357
A split S2 on auscultation
ASD (delayed closure of pulmonic valve)
358
What is a paradoxical embolus?
DVT --> through an ASD into the systemic circulation
359
PDA is associated with which maternal infection?
Rubella
360
The ductus arteriosus connects...
Pulmonary artery and aorta
361
Holosystolic machine-like murmur
PDA
362
Eisenmenger syndrome of a PDA results in...
Lower extremity cyanosis
363
Which drugs close PDA vs. keeps it open
Close: indomethacin (decreases PGE --> PDA closure)
364
Tetralogy of Fallot results in what type of shunt?
PA stenosis, RVH, VSD, overriding aorta [R-->L]
| * Relieved by squatting to increase arterial resistance
365
The degree of the _________ determines the extent of shunting and cyanosis in a TOF patient.
Stenosis
366
A boot shaped heart on CXR
TOF
367
Transposition of the great vessels can be managed (temporarily) with what treatment (non-surgical)
Aorta/Pulmonary artery switched: only survival --> maintain PDA with PGE2
368
Transposition of the great vessels is associated with what maternal condition?
Maternal diabetes
369
Truncus arteriosus
Single large vessel arising from both ventricles; truncus fails to divide
370
Tricuspid atresia is associated with what septal defect?
ASD
371
Infantile vs. Adult coarctation of the aorta
Infantile: PDA [proximal to the PDA]; associated with Turner syndrome [cyanosis LE]
Adult: not associated with PDA [HTN UE, hypotension LE]; rib notching
372
Infantile coarctation of the aorta is associated with what syndrome?
Adult form of coarctation of the aorta has what odd association?
Turner syndrome; bicuspid aortic valve
373
Most common overall cause of bacterial endocarditis.
S. viridans [infects previously damaged valves]
374
Describe the pathogenesis of subacute bacterial endocarditis
Exposure of subendothelial collagen; thrombotic vegetations (platelets and fibrin); transient bacteriemia leads to TRAPPING of bacteria in vegetations
375
IVDU acute endocarditis infects which valve?
Tricuspid valve
376
Key bug that causes endocarditis of prosthetic valves
S. epidermidis
377
Key bug that causes endocarditis in patients with underlying colorectal carcinoma
S. bovis
378
Culture negative endocarditis
HACEK
| * Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella
379
Consequences of septic embolization of cardiac emboli.
Janeway lesions: painless
| Osler nodes: painful IC deposition
380
Nonbacterial thrombotic endocarditis can be associated with... (2 conditions)
Hypercoagulable state, underlying adenocarcinoma
381
Most common form of cardiomyopathy.
Dilated (systolic/bi-ventricular)
382
High yield causes of dilated cardiomyopathy.
Genetic mutations (AD), myocarditis (Coxsackie), ETOH abuse, drugs (cocaine, doxorubicin), pregnancy
383
Treatment of dilated cardiomyopathy.
Transplant
384
AD cause of hypertrophic cardiomyopathy
Sarcomere (beta-myosin heavy chain)
385
Histologic hallmark of hypertrophic cardiomyopathy
Myofiber disarray
386
Causes of restrictive cardiomyopathy.
Amyloidosis, Sarcoidosis, Hemochromatosis, Loeffler syndrome (Ascaris), Endocardial fibroelastosis (children)
387
Loeffler syndrome
Ascaris; can p/w restrictive CM
388
Restrictive cardiomyopathy EKG findings
Low voltage EKG with diminished QRS amplitudes
389
Most common primary cardiac tumor in adults
Cardiac myxoma
| * Benign mesenchymal proliferation with a gelatinous appearance; abundant ground substance on histology
390
Where does cardiac myxoma grow and what would the patient p/w?
Pedunculated mass in left atrium; syncope
391
Benign hamartoma of cardiac ventricular muscle (association with what syndrome -- children).
Rhabdomyoma; associated with tuberous sclerosis
392
Mets to the heart usually results in
Pericardial effusion (breast, lung cancer, melanoma, lymphoma)
393
Acute rheumatic fever & molecular mimicry. Explain
M proteins resemble proteins in human tissues = molecular mimicry
394
JONES Criteria
```
J: Joint problems (mig poly)
O: pan carditis
N: nodules SC
E: erythema marginatum
S: chorea
```
395
Aschoff body with Anitzkow cells
Rheumatic fever myocarditis: focus of chronic inflammation with Anitzkow cells (histiocytes with caterpillar nucleus)
396
What is the one thing that will kill a patient with acute rheumatic fever?
Myocarditis; Aschoff body with Anitzkow cells
397
Chronic rheumatic valvular stenosis involves which valve?
Mitral valve; scarring of the valve with fusion of the commisures
398
Does bicuspid valve predispose you to AS?
Yes (think adult coarctation of the aorta)
399
In order to prove rheumatic heart disease, one valve MUST be involved: mitral or aortic.
Mitral
400
Can microangiopathic hemolytic anemia be caused by aortic stenosis?
Yes
401
What is the most common cause of aortic regurgitation?
Dilation of the aorta [think aortic aneurysm]
402
Early, blowing diastolic murmur
AR
403
Hyperdynamic circulation
Regurgitation of blood, SV increases, SBP increases, DBP decreaes (PP widens); bounding pulses, head bobbing, pulsatile nail beds
404
Eccentric hypertrophy vs. Concentric hypertrophy
Eccentric: volume overloaded
Concentric: pressure overload
405
Mitral valve prolapse
Associated with Marfan's, EDS
406
Mid-systolic click
MVP
407
Holosystolic blowing murmur
Mitral regurgitation
408
Opening snap followed by diastolic rumble
Mitral stenosis
409
Innermost layer of a blood vessel; Middle and outermost
Tunica intima (endothelial cells on a BM), media (smooth muscle), adventitia (C/T)
410
Organ ischemia can occur through
Thrombosis, Fibrosis
411
Giant cell arteritis
>50 y.o. females; branches of carotid artery [flu like, polymyalgia rheumatica]
412
Polymyalgia rheumatica
Giant cell arteritis
413
Bx findings giant cell arteritis
Granulomatous vascultis with intimal fibrosis; segmental vasculitis (negative bx doesn't always R/O disease)
414
Takayasu arteritis
Same disease as GCA; adults < 50 years old (young Asian female)
* Aortic arch at branch points
* Pulseless disease
415
Which large vessel vasculitis is considered pulseless disease in young Asian females?
Takayasu arteritis
416
Medium vessels arteries involve (what type of artery)
Muscular arteries
417
Polyarteritis nodosa spares what organ? Is associated with what Ag?
Necrotizing vasculitis; lungs spared; HTN (renal); abdominal pain (mesenteric artery); HbSAg
418
A string-of-pearls appearance within a context of varying degrees of fibrinoid necrosis and fibrosis is characteristic of which vasculitis?
Polyarteritis nodosa (PAN)
419
Highlighter pink of a blood vessel wall is characteristic of which type of vascular injury?
Fibrinoid necrosis
420
Kawasaki disease
Asian children < 4 y.o.; fever, conjunctivitis, rash palms/soles, cervical LAD
* Thrombosis with MI/aneurysm with rupture
421
Treatment of Kawasaki disease
ASA, IVIG
422
Under what circumstance do you use ASA to treat a child with a 'viral'-type illness?
Kawasaki disease
423
Which vasculitis in children is associated with a palmar/sole rash?
Kawasaki
424
Buerger disease
Necrotizing vasculitis involving digits; presents with ulceration, gangrene, autoamputation of fingers and toes
* Raynaud phenomenon is often present
* Highly associated with smoking
425
Wegener's granulomatosis
Nasopharynx, lungs, kidneys (RPGN); C-ANCA+; cyclophosphamide
426
Large necrotizing granulomas with necrotizing vasculitis in NP, lungs, kidney; key treatment?
Cyclophosphamide (Wegener's)
427
Microscopic polyangiitis is similar to Wegener's. What are the differences?
Necrotizing vasculits involving multiple organs, lung and kidney
* No NP involvement and no granulomas (P-ANCA)
428
Churg-Strauss Syndrome is distinguised from microscopic polyangiitis with which 3 features? Both are p-ANCA positive.
1. Granulomas
2. Asthma
3. Eosinophilia
429
Palpable purpura on buttocks and legs; gi pain/bleeding; hematuria; follows URTi
HSP / IgA Nephropathy
430
Renal artery stenosis (lab value of importance; finding on CT)
* Increased renin
| * Unilateral atrophy
431
2 high yield causes of renal artery stenosis (elderly male vs. young female)
1. Atherosclerosis
| 2. Fibromuscular dysplasia
432
Acute renal failure, headache, papilledema
Malignant htn emergency
433
3 pathologic patterns of arteriosclerosis
1. Atherosclerosis [intima]
2. Arteriolosclerosis
3. Monckeberg medial sclerosis [media]
434
Hyaline vs. Hyperplasitc arteriolosclerosis
Hyaline: protein
Hyperplastic: smooth muscle
435
4 most common arteries affected by atherosclerosis
Abdominal aorta, Coronary, Popliteal, ICA
436
4 modifiable risk factors for atherosclerosis
1. HTN
2. HLD
3. Smoking
4. DM
437
Fatty streak in blood vessels
Seen in teenagers (early atherosclerosis)
438
Symptomatic atherosclerosis occurs with critical stenosis at what percentage?
70%
439
Hallmark of atherosclerotic embolus
Cholesterol cleft
440
Hyaline and hyperplastic; arteriolosclerosis causes
1. Hyaline: proteins [pink] - benign HTN/DM (NEG-leaky)
| 2. Hyperplastic: malignant HTN
441
Glomerular scarring 2/2 benign HTN.
| * Histologic hallmark of arteriole.
Hyaline arteriosclerosis of renal arteriole
442
Onion-skin hyperplastic arteriolosclerosis is 2/2
Malignant HTN
443
Flea-bitten appearance of kidney
Fibrinoid necrosis 2/2 malignant hypertension
444
Monckeberg medial calcific sclerosis
Non-obstructive; non clincally significant; incidental finding on X-ray or Mammography
445
Aortic dissection is 2/2
| What is the histologic hallmark?
Intimal tear 2/2 HTN
| * Occurs within the context of pre-existing weakness of the media
446
Vaso vasorum are present in which tunica in the proximal 10cm of the aorta?
Adventitia
| Hyaline arteriosclerosis of vasovasorum; decreased Q to the outer part of blood vessel wall
447
```
Sharp, tearing, chest pain that radiates to the back;
#1 cause of death
```
```
Aortic dissection;
Cardiac tamponade (dissection backwards); rupture into mediastinum (hemorrhage); ruptre forwards (renal artery compression)
```
448
What is the highest yield cause of a thoracic aneurysm? Complications?
Balloon-like dilation of the thoracic aorta
* Tertiary syphillis; tree-bark appearance of aorta
* Aortic insufficiency (#1), compression of mediastinal structures, thrombosis/embolism
449
AAA occurs 2/2 atherosclerosis in what part of the aorta?
Below renal arteries, but above the bifurcation
450
A pulsatile abdominal mass that grows with time. What is the critical size most associated with rupture? What are the S/S of rupture?
AAA
| > 5 cm; Hypotension, pulsatile mass, flank pain
451
T/F Hemangioma often regresses during childhood. Is it blanching?
True; Benign tumor of BV
| Yes, blanches (vs. purpura which doesn't blanch)
452
Angiosarcoma is a malignant proliferation of endothelial cells. Liver angiosarcoma is associated with...
PVC, Arsenic, Thorotrast
453
Low-grade malignant proliferation of endothelial cells. Is it blanching?
KS (HHV-8)
| * Can involve skin/visceral organs [non-blanching]
454
KS is seen in... (3 different patient demographics). How do you treat each group?
E. European males (surgery), AIDS (ARV), transplant recipients (decreased IS)
455
Cystic tunica medial necrosis
Dissection
456
Rheumatic fever is associated with Aschoff bodies which are...
Noncaseating granulomas with giant cells
457
Most commmon cause of rhinitis
Adenovirus
458
Allergic rhinitis is associated with...
Asthma and eczema
459
Nasal polyps occur in... (3 conditions)
Cystic fibrosis, ASA-intolerant asthma, repeated bouts of rhinitis
460
Profuse epistaxis in adolescent males
Angiofobroma (benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue)
461
Nasopharyngeal carcinoma with cervical LAD is associated with which virus in which 2 demographics?
EBV: African children and Chinese adults [pleomorphic keratin-positive epithelial cells in the background of lymphocytes]
462
Acute epiglottitis caused by which microbe?
H. flu type B [high fever, sore throat, droling, dysphagia, acute airway obstruction]
463
Croup [hoarse barking cough and inspiratory stridor] is caused by...
Parainfluenza virus
464
Vocal cord nodules 2/2
Excessive use; myxoid degeneration [resolves with rest]
465
Laryngeal papilloma is due to which virus? Single/Double; Adults/Children
HPV 6 & 11 [single in adults; multiple in children]
466
Laryngeal carcinoma risk factors...
ETOH, tobacco
467
Parietal and visceral pleura are lined by what type of cells?
Mesothelial cells
468
Spontaneous PTX; tracheal shift
Rupture of emphysematous bleb in a young male [shift toward the side of PTX]
469
Tension PTX; tracheal shift
Shift to opposite side of injury 2/2 penetrating chest injury
470
Mesothelioma p/w
Recurrent pleural effusions, chest pain [massive encasement of the lung]
2/2 asbestos exposure
471
Pulmonary HTN histopathology
1. Atherosclerosis of pulmonary trunk
2. Smooth muscle hypertrophy
* * 3. Plexiform lesions tuft of capillaries**
472
Young female p/w exertional dyspnea
Pulmonary hypertension
473
Familial forms of pulmonary hypertension is associated with inactivating mutations of...
BMPR2 [leads to proliferation of vascular smooth muscle]
| * Plexiform lesions
474
Recurrent PE can lead to...
Pulmonary HTN
475
ARDS histologic hallmark & CXR classical findings
Leaking of protein rich fluid: hyaline membranes
| * White out
476
Ventilator setting in ARDS
PEEP: positive end-expiratory pressure
477
Recovery in ARDS can lead to interstitial fibrosis because...
You've knocked out the type 2 pneumocytes [stem cells]
478
Neonatal RDS arises 2/2
* X-ray finding
* Associated with
Inadequate surfactant levels
* Diffuse granularity of lung
* * Prematurity L:S ratio (low <2), C-section, maternal DM
479
Major component of surfactant
Phosphatidylcholine = Lecithin
480
T/F Steroids promote the development of surfactant.
True
481
Insulin inhibits/promotes surfactant production
Inhibits
482
Hypoxemia in a neonate increases the risk for..
Supplemental O2 increases risk for...
Persistence of PDA, necrotizing enterocolitis; supplemental O2 increases risk of free radical injury [blindness]
483
Radon associated with which cancer...
Lung cancer
484
In the Western US, you would think of what infectious cause of a coin lesion?
Histoplasma
485
A benign mass of disorganized lung tissue + cartilage seen as a calcified mass on X-ray
Hamartoma
486
SCLC: surgical or radiotherapy
Radiotherapy
487
Lung cancer subtypes (NSCLC)
1. Glands/Mucus:
2. Keratin pearls/Intercellular bridges
1. AC
2. Squamous CC
3. Large cell
488
Small cell
ADH, ACTH, LES
489
Tumors start with "s" are associated with ...
1. Smokers
2. Cental
3. Paraneoplastic
490
Squamous cell carcinoma is associated with which paraneoplastic syndrome?
PTHrP
491
Most common lung tumor in non-smokers and female smokers
Adenocarcinoma
492
Bronchioalverolar carcnioma arises from which type of cells?
Clara cells; not related to smoking (PNA like consolidation)
493
Chromogranin+ lung tumor
Carcinoid [polyp like tumor; nests of cells]
494
2 types of neuroendocrine tumor in lung
1. SCLC (non-well-differentiated)
| 2. Carcinoid (well-differentiated)
495
Cannonball tumors on lung imaging is usually indicative of primary malignancy of ... (2)
Breast, colon; Mets
496
Adrenal gland mets primary site of malignancy
Lung
497
Complications of lung cancer (based on the anatomy of the lung)
Pleural involvement, obstruction of SVC, involvement RLN, phrenic nerve; Horner's
498
Which type of lung cancer most commonly spreads to involve the pleura (not mesothelioma)
Adenocarcinoma
499
Decreased TLC, very low FVC, FEV1, but increased FEV1:FVC is characteristic of...
Restrictive lung disease
500
Obesity can result in restrictive or obstructive lung disease.
Restrictive
501
Bleomycin, Amiodarone, Radiation therapy can cause...
(Idiopathic) pulmonary fibrosis
502
TGF-beta from injured pneumocytes can drive...
Idiopathic pulmonary fibrosis
503
Subpleural --> Diffuse honeycombing of lung is characteristic of which lung disorder?
Idiopathic pulmonary fibrosis
504
Pneumoconioses mediated by which cell in the lung?
I/S fibrosis 2/2 small particles chronic exposure; mediated by macrophages
505
Coal workers pneumoconoisis
Carbon dust seen in coal miners; black lung
506
Caplan syndrome
Coal workers pneumoconoisis associated with RA
507
Anthracosis
Build-up of carbon (not clinically significant)
508
Silicosis increaes risk for which infectious disease?
Exposure to sand-blasting and silica miners; impairs phagolysosome to form --> fibrotic nodules in upper lobes of lung; TB
509
Aerospace industry exposure: non-caseating granulomas in lung, hilum
Beryllium
510
Shipyard, construction, plumbers
1. Fibrosis lung/pleura
| 2. Cancer lung/pleura
511
Long rod-shaped particles with brown beads in the lung (Ferrigunous body)
Asbestos
512
Asteroid body
Sarcoidosis non-caseating granuloma
513
AA female p/w dyspnea, cough, elevated ACE, hypercalcemia [1-alpha hydroxylase can activate vitamin D]
Sarcoidosis
514
Hypersensitivity pneumonitis
Granulomatous reaction to inhaled antigen; p/w fever, cough, dyspnea; chronic exposure to lead to I/S fibrosis
** Eosinophils
515
4 COPD disorders
Obstruction to getting air out of the lung
* Emphysema
* Chronic bronchitis
* Bronchiectasis
* Asthma
516
What is the only increased value on spirometry in COPD?
TLC
517
Chronic bronchitis Reid Index
>50%
518
2 types of submucosal glands in the lung; normal ratio in the lung? What index is this called?
Serous, mucinous glands
| < 40% [Reid index]
519
Blue bloaters
Chronic bronchitis
520
Destruction of alveolar air sacs occurs in what COPD? What is the underlying pathophysiology?
Emphysema
| [loss of elastic recoil and collapse of the small airways; balloon vs. shopping bag]
521
What are the 2 values increased on spirometry in COPD?
TLC, FRC
522
Chronic bronchitis Reid Index
>50%
523
2 types of submucosal glands in the lung; normal ratio in the lung? What index is this called?
Serous, mucinous glands
| < 40% [Reid index]
524
Blue bloaters
Chronic bronchitis
525
Destruction of alveolar air sacs occurs in what COPD? What is the underlying pathophysiology?
Emphysema
[loss of elastic recoil and collapse of the small airways; balloon vs. shopping bag]
* Protease / anti-protease imbalance
526
Panacinar vs. Centriacinar emphysema; upper/lower lobes
Panacinar: A1AT deficiency [lower lobes] -- ER of hepatocytes
Centriacinar: Smoking [upper lobes -- smoke goes up]
527
Round, purple globules in hepatocytes; associated with emphysema; PAS+
A1AT deficiency
528
A1AT: accumulation of protein in what organelle of the hepatocyte
Endoplasmic reticulum
529
Curschmann spirals admixed with Charcot-Leyden seen in...
Asthma;
* Mucus plugging
* Eosinophilic MBP
530
Nasal polyps are classically seen in allergic rhitinis. Where else can they be seen in adults? Children?
ASA-intolerant: adults
| CF: Children
531
FRC emphysema vs. fibrosis
Emphysema: increased
Fibrosis: decreased
532
Asthma is defined as...
Reversible airway bronchocontrsiction
533
T/F Allergens induce Th2 in asthma.
True: Il-4 (class switch), 5 (eosinophils), 10 (inhibts Th1)
534
Nasal polyps are classically seen in allergic rhitinis. Where else can they be seen in adults? Children?
ASA-intolerant: adults
| CF: Children
535
Permanent dilation of bronchioles and bronchi (larger airways) 2/2 necrotizing inflammation with damage to airway walls
Bronchiectasis; blow out of a straw vs. blowing out of a pipe
536
T/F bronchiectasis can lead to secondary amyloidosis
True
537
Conjoined kidneys connected at lower pole; ascension stopped by what artery?
Horseshoe kidney (IMA)
538
Complication of unilateral renal agenesis
Hypertrophy of existing kidney; hyperfiltration increases risk of renal failure later in life
539
Oligohydramnios is associated with...
Bilateral renal agenesis; lung hypoplasia; flat face with low set ears (Potter Sequence)
540
Potter sequence is associated with...
Bilateral renal agenesis; lung hypoplasia, flat face with low set ears and extremity defects
541
Noninherited, congenital malformation of renal parencyhma characterized by renal cysts and abnormal tissue (cartilage)
Dysplastic kidney
* Non-inherited
542
What is on the differential for ARPKD?
Dysplastic kidney (non-inherited)
543
T/F ARPKD can p/w Potter Sequence
True
544
A baby p/w portal hypertension
ARPKD (hepatic fibrosis)
545
ADPKD extra-renal manifestations (3 key ones)
Berry aneurysm, hepatic cyst, MVP [increased renin]
546
AD defect: cysts in medullary collecting ducts w/ parenchymal fibrosis in shrunken kidneys
Medullary cystic kidney disease
547
Hallmark of acute renal failure
Azotemia
548
BUN:Cr ratio in pre-renal ARF
>15; tubular function intact
549
BUN:Cr ratio in post-renal ARF
2%; urine osmolality < 500 (decreased ability to [urine]
550
Injury and necrosis of tubular epithelial cells: brown, granular casts in urine
ATN (BUN:Cr < 15)
551
2 major etiologies of ATN
Ischemic: B/S; PCT & Thick ascending limb of medulla
Toxic: PCT
552
Toxic etiologies of ATN
AG, lead, myoglobinuria, ethylene glycol, radiocontrast dye, urate
553
Drug induced hypersensitivity reaction of intersititum and tubules that results in ARF
Acute I/S nephritis
554
Chronic analgesic abuse, DM, SC disease, sever acute pyelo can cause
Acute papillary necrosis
555
Alkaline urine with ammonia scent UTI
Proteus
556
Pyuria with negative urine culture suggests
Urethritis 2/2 Chlamydia trachomatis or N. gonorrhoeae
557
Pt p/w fever, flank pain, WBC casts and leukocytosis
Pyelonephritis
558
Chronic pyelo in a child is usually 2/2
VUR
559
Renal cortical scarring with blunted calyces
Chronic pyelo
560
Scarring at upper and lower poles of kidney
Chronic VUR
561
Thyroidization of the kidney
Chronic VUR/pyelonephritis
562
Colicky pain with hematuria and unilateral flank tenderness
Kidney stone
563
Ca oxalate, Ca phosphate kidney stone
Most common; hypercalcemia; idiopathic hypocalciura
564
What type of kidney stone is seen in Crohn's disease and why?
Ca oxalate stone; Increased absorption of oxalate (binds Ca)
565
AMP stone that results in a staghorn calculus is generally caused by..
Infection with Proteus, Klebsiella; can develop UTI's --> surgical removal
566
Radiolucent kidney stone
Uric acid; treat with hydration and alkalinization of the urine
567
Cysteine stones are seen in children with
Cystinuria [can also form staghorn calculus]
568
Staghorn calculus in an adult vs. child
Adult: Proteus, Klebsiella
Child: Cystinuria
569
Most common causes of ESRF
DM, HTN, glomerular disease
570
Most common cause of chronic rejection in a lung transplant patient
Destruction of the small airways
571
Nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy, deposition of urea crystals in skin
Azotemia
572
EPO produced by what cells in the kidney?
Peri-tubular interstitial cells
573
2 reasons ESRF patients develop hypocalemia
1. Vitamin D
| 2. HyperPO4 binds free Ca
574
Osteitis fibrosis cystica
2/2 hyper PTH
575
Osteomalacia vs. Osteoporosis
Cannot mineralize osteoid; buffered metabolic acidosis from bone Ca
576
T/F Patients with ESRF can develop cysts in the context of shrunken kidneys while on dialysis.
T
577
Renal hamartoma comprised of blood vessels, smooth muscle and adipose tissue is increased in frequency in patients with what disorder (also causes seizures)
Renal angiomyolipoma; Tuberous sclerosis
578
Triad of hematuria, palpable mass and flank pain
RCC
579
T/F RCC can p/w L varicocele
T (Spermatic vein drains into L renal vein)
580
What color is gross mass of RCC? Most common subtype?
Yellow; clear cell
581
Pathogenesis of RCC
Loss of VHL (3P) tumor supressor gene [increased IGF-1 and increased HIF VEGF and PDGF]
582
VHL disease inheritance & 2 cancers
AD; RCC & hemangioblastoma of cerebellum
583
RCC typically spreads to which nodes?
Retroperitoneal
584
Malignant kidney tumor comprised of blastema, primitive glomeruli and tubules and stromal cells in a child [p/w hematuria and HTN]
Wilms Tumor [WT1 mutation]
585
WAGR syndrome
Wilms, Aniridia, Genital abnormalities, mental and motor retardation
586
Beckwith-Wiedemann Syndrome
Wilms Tumor, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly (tongue)
587
Most common type of Lower UT cancer; #1 risk factor
Urothelial carcinoma; polycyclic hydrocarbons, napthylamine, azo dyes, LTM cyclophosphamide, phenacetin
588
2 distinct pathways of urothelial carcinoma
1. Papillary [low to high grade]
| 2. Flat [Begins as high grade]
589
Which subtype of urothelial carcinoma is associated with early p53 mutations?
Flat
590
Urothelial tumors typically display a field defect. What is this?
So many mutations develop over time leads to multifocal nature and recurrence
591
SCC of the bladder 2/2
Chronic cystitis, *Schistosoma hematobium [Middle Eastern Male]*, long standing nephrolithiasis
592
Adenocarcinoma of bladder at the dome of the bladder arises 2/2
** Arises from urachal remnant **, cystitis glandularis, extrosphy
593
Urachus
Yolk sac to fetal bladder [lined by glanduar epithelium]; its remnant can lead to AC of the bladder
594
Hypercoagulable state in nephrotic syndrome 2/2
Loss of AT3
595
T/F Minimal change disease can be associated with Hodgkins Lymphoma
True
596
Disease: Effacement of foot processes of podocytes on EM 2/2 cytokine proliferation. What type of protein is lost?
Minimal change disease [selective loss of albumin]
597
Most common cause of neprotic syndrome in AA & Hispanics? Common diseases?
FSGS
| HIV, heroin, SCD
598
FSGS immune complex deposits? Yes or No
No: negative IF
599
Kidney disease associated with HBV, solid tumors, SLE, drugs (ie. NSAIDS, penicillamine)
Membranous Nephropathy
600
Subepithelial spike and dome appearance; granular IF
Membranous nephropathy
601
Thick capillary membranes on H&E with tram-track appearance; granular IF [Type I & 2]
MPGN
Type I: subendothelial [HBV, HCV -- more often assoc. w tram tracks]
Type II: within BM [Anti C3 nephritic factor Ab / stabalizing Ab]
602
Anti-C3 nephritic factor Ab (which stabilizes the C3 convertase and overactivates complement)
Type 2 MPGN
603
Preferential hyaline arteriosclerosis in DM nephropathy in which vessel: afferent or efferent? What treatment is indicated to slow progression of hyperfiltration induced damage?
Efferent; ACE inhibitor helps because you don't want to squeeze down too much on efferent vessel.
604
M protein virulence factor and renal disease
PSGN
605
Subepithelial humps on EM
PSGN
606
RPGN IF
1. GBM [linear]
2. Granular
3. Vasculitis [negative IF]
607
Crescent in RPGN is composed of...
Fibrin & macrophages
| [Not collagen]
608
Granular IF means...
Immune complex deposition
609
Diffuse proliferative GN (with subendothelial deposits) is seen in what systemic AI disease?
SLE
610
CS vs. Microscopic polyangiitis
IN CS:
1. Eosinophils
2. Granulomatous inflammation
3. Asthma
611
Isolated hematuria with sensory hearing loss and ocular disturbances
Alport syndrome; inherited defect in collagen 4 (X-linked); thinning and splitting of GBM
612
Developmental malformation; pancreas forms a ring around the duodenum; risk of duodenal obstruction
Annular pancreas
613
Premature activation of _____________ leads to activation of other enzymes in acute pancreatitis.
Trypsin
614
What types of necrosis do you see in acute pancreatitis?
Liquefactive necrosis of pancreas; fat necrosis of peri-pancreatic fat
615
2 most common causes of acute pancreatitis
1. ETOH (contracts sphincter)
| 2. Gallstones (ampulla)
616
Automobile accident in child wearing a seatbelt can cause...
Acute pancreatitis.
617
Measles, mumps or rubella: Acute pancreatitis
Mumps
618
Lipase or amylase: which is better marker for acute pancreatitis?
Lipase [amylase from salivary gland]
619
Persisentece of elevated amylase in the face of resolved acute pancreatitis
Pancreatic pseudocyst, abscess
620
Most common causes of chronic pancreatitis [adults vs. children]
1. ETOH: adults
| 2. CF: children
621
Pancreatic AC arises from...
Pancreatic ducts
622
2 major risk factors for pancreatic AC
1. Smoking
| 2. Chronic pancreatitis
623
Pancreatic cancer at the head of the pancreas can p/w [vs. body/tail]
Painless jaundice, pale stools and a palpable gallbladder; 2ndary DM
624
Serum tumor marker for pancreatic AC
CA 19-9
625
Failure to form or early destruction of extrahepatic biliary tree p/w neonatal jaundice and cirrhosis
Biliary atresia
626
Precipitation of cholesterol or bilirubin in bile results in...
Gallstones; supersaturated, decreased lecithin or bile acids [solublize the choleterol]; stasis
627
What is the classical drug that can lead to gallstones?
Cholestyramine
628
Are cholesterol stones radiolucent or radioopaque?
Radiolucent
629
T/F Estrogen increases activity of HMG CoA reductase.
True
630
Bilirubin stones are radiolucent or opaque?
Opaque
631
6 key complications of gallstones
1. Biliary colic [waxing/waning]
2. Acute cholecystitis
3. Chronic cholecysitis [Rokitishinky-Ashoff sinus]
4. Gallbladder cancer
5. Ascending cholangitis (GNR)
6. Gallstone ileus
632
Lab value increased in acute cholecysitis [besides WBC]
Increased ALP
633
Rokitishinky-Ashoff sinus
Chronic cholecystitis; mucosa diving down into the smooth muscle
634
Late complication of chronic cholecystitis seen on X-ray
Porcelain gallbladder [dystrophic calcification]
635
A gallstone ileus can lead to ...
Fistula formation b/t the gallbladder and duodenum
636
Cholecystitis in an elderly woman raises suspicion for...
Adenocarcinoma of the gallbladder
637
Is UC bilirubin water soluble?
No
638
Pitch black liver; what other condition has the same pathophysiology, but no black liver?
Dubin-Johnson Syndrome
| * Rotor syndrome
639
Pruritis in obstructive jaundice is 2/2
Plasma bile acids
640
Viral hepatitis caused by viruses other than hepatitis...
EBV, CMV
641
Which hepatitis virus in a pregnant woman is most worrisome?
HEV
642
First serologic marker to rise in acute HBV infection; its presence >6 months defines chronic state
HBsAG
643
The presence of which Ab defines resolved or immunized HBV infection?
HBsAB IgG
644
HDV co-infection vs. superinfection. Which is more severe?
Superinfection (different times) is more severe than co-infection (same time)
645
Fibrosis in cirrhosis is mediated by which type of cell?
Stellate cell (TGF-beta)
646
Can cirrhosis lead to hypersplenism?
Yes
647
3 patterns of pathology seen in alcoholic liver disease
1. Fatty liver
2. ETOH hepatitis (acetaldehyde)
3. Cirrhosis
648
Damaged intermediate filaments within hepatocytes
Mallory bodies
649
AST or ALT is located in the mitochondria?
AST
650
Damage in hemochromatosis is caused by...
Free radicals (Fenton reaction)
651
The key regulatory step in iron absorption
Enterocyte [C282Y mutation in HFE]
652
Cirrhosis, secondary DM, bronze skin, cardiac arrhythmia and gonadal dysfunction
Hemochromatosis
653
Brown pigment in hepatocytes; one stains blue with Prussian blue
Iron vs. Lipofuscin (not blue)
654
ATP7B gene mutated in...
Wilson disease
655
Treatment of Wilson disease
D-penicillamine
656
AI granulomatous destruction of intrahepatic bile ducts. Which antibody?
PBC; anti-mitochondrial Ab
657
Inflammation and fibrosis of intra and extra-hepatic bile ducts; leads to periductal fibrosis with onion-skin appearance, beaded on imaging
PSC
658
p-ANCA & UC association with which hepatic disease?
PSC
659
PSC patients have an increased risk for
Cholangiocarcinoma
660
Pathophysiology of Reye's syndrome
Mitochondrial damage of hepatocytes
661
What type of benign tumor of hepatocytes is associated with OCP usage?
Hepatic adenoma
662
T/F HCC can lead to Budd-Chiari syndrome
T
663
Hepatomegaly with a nodular free edge of the liver raises suspicion for...
Mets to the liver
664
Failure of facial prominennces to fuse
Clef lip and palate
665
Painful, superficial ulceration of oral mucosa. Arises in relation to stress, but often recurs. Characterized by grayish base surrounded by erythema
Aphthous ulcer
666
Syndrome of recurrent aphthous ulcers, genital ulcers and uveitis. Due to immune complex vasculitis involving small vessels
Behcet syndrome
667
Virus that remains dormant in the ganglia of the trigeminal nerve.
Herpes-1
668
Major risk factors for SCC mouth (floor of mouth)
Tobacco, ETOH
669
Leukoplakia vs. Erythroplakia (Which is most associated with squamous dysplasia?
Must bx to r/o carcinoma.
| Erythroplakia (angiogenesis)
670
Oral hairy leukoplakia on the lateral aspect of the tongue is due to what virus? Any risk for cancer?
EBV in AIDS patients (no increased cancer risk)
671
Orchitis, pancreatitis, aspetic meningitis associated with what virus?
Mumps
672
Does an elevated amylase in a patient with mumps suggest pancreatitis?
Not necessarily (salivary amylase)
673
Inflammation of salivary gland usually due to S. aureus infection is called
Sialadenitis
674
Benign tumor of stromal (cartilage) and epithelial (glands) tissue of salivary gland which presents as a mobile, painles, circumscribed mass at the angle of the jaw
Pleomorphic adenoma
675
Why is there a high rate of recurrence of a pleomorphic adenoma?
Irregular margins
676
Benign cystic tumor with abundant lymphocytes and germinal centers; arises in parotid
Warthin tumor
677
Malignant tumor composed of mucinous and squamous cells. Usually arises in parotid and involves the facial nerve
Mucoepidermoid carcinoma
678
Congenital defect resulting in connection between esophagus and trachea is called:
TEF; polyhydramnios
1. Vomiting
2. Polyhydramnois
3. Abdominal distension
679
Thin protrusion of esophageal mucosa, most often in the upper esophagus results in obstruction. P/W dysphagia for poorly chewed food.
Esophageal web [increased risk SCC]
680
Esophageal web, beefy-red tongue (2/2 atrophic glossitis), severe iron deficiency anemia
Plummer-Vinson syndrome
681
Outpouching of pharyngeal mucosa through an acquired defect in the muscular wall; arises above UES at junction of esophagus and pharynx. P/W dysphagia, obstruction and halitosis
Zenker diverticulum
682
A Zenker diverticulum is a true or false?
False
683
Painful hematemesis in an alcoholic or bulemic patient
Mallory-Weiss Syndrome
684
Boerhaave syndrome
Rupture of esophagus; air in mediastinum (SC emphysema)
685
Dilated submucosal veins in the lower esophagus 2/2 portal hypertension. Painless hematemesis.
Esophageal varices
686
Most of the esophageal venous blood drains into the _________________ which then drains into the SVC
Azygous vein
687
The left gastric vein drains into the _______________________.
Portal vein
688
Painless vs. painful hematemesis
Painless: esophageal varices
Painful: MW
689
#1 cause of death in cirrhosis
Esophageal varices
690
Disordered esophageal motility with inability to relax LES; 2/2 damaged ganglion cells in myenteric plexus. Known infectious association?
Achalasia [Bird-beak sign]
| * Chagas disease
691
Bird beak sign on barium swallow
Achalasia
692
Where is the myenteric plexus?
In the muscularis layer between the inner circular and outer longitudinal muscular layers
693
Chagas disease an the esophagus
Achalasia
694
High LES pressure on esophageal manometry
Achalasia
695
Sliding hiatal hernia [hourglass appearance]
Stomach herniates upward into the esophagus
696
T/F Hiatal hernia is a risk factor for GERD
True
697
Para-esophageal hernia
Much less common; bowel sounds in lower lung fields.
698
Bowel sounds in lower lung fields as well as lung hypoplasia is usually due to:
Paraesophageal hiatal hernia
699
Adult onset asthma usually 2/2
GERD [heartburn, tooth erosion]
700
How can strictures appear in the esophagus?
Mucosal ulceration in GERD healed by fibrosis
701
Most common esophageal cancer worldwide
SCC esophagus [ETOH, tobacco, hot tea, achalasia, web, injury]
702
Lymph node spread: upper, middle, lower 1/3 esophagus
Upper: cervical
Middle: mediastinal or tracheobronchial
Lower: Celiac or gastric
703
Congenital malformation of the abdominal wall; leads to exposure of abdominal contents
Gastroschisis
704
Persistent herniation of bowel into the umbilical cord 2/2 failure of herniated intestines to return to body cavity. Contents are covered by peritoneum and amnion of UC
Omphalocele (Seeled)
705
Congenital hypertrophy of pylorus p/w projectile non-bilious vomiting 2 weeks. Visible peristalsis; olive-like mass in abdomen.
Pyloric stenosis
706
Acid damage to gastric mucosa 2/2 imbalance between mucosal defenses and acidic environment
Acute gastritis
707
Curling vs. Cushing ulcer
Curling: burn
Cushing: increased ICP
708
Why do critically ill patients get gastric ulcers?
1. Hypovolemia leads to decreased clearance of acid and decreased mucosal protection
2. Increased ICP: Inc. ACh
709
3 receptors on parietal cells that can increase acid production
1. Gastrin
2. Histamine
3. ACh
710
Erosion vs. ulcer
Erosion: loss of epithelium
Ulcer: loss of mucosal layer
711
AI destruction of parietal cells of body/fundus. Type 4 hypersensitivity. Antibodies are a side-effect of the damage
Chronic gastritis
* Atrophy of mucosa
* Achlorhydria [increased gastrin and G cell hyperplasia]
712
What are the 4 key regions of the stomach?
Cardia, fundus, body, antrum
713
Chronic inflammation of the stomach increases risk for...
Intestinal metaplasia (Peyer's pataches) and gastric AC
714
Describe the underlying reason for intestinal metaplasia in the stomach with chronic gastritis.
Peyer's patches/inflammation
715
Does H. pylori invade? What is the most common location in the stomach?
No; antrum
716
What type of lymphoma is associated with H. pylori?
Marginal zone (MALT)
717
Epigastric pain that improves with meals
Duodenal ulcer
718
Brunner glands
Produce mucus; hypertrophied in duodenal ulcer
719
Posterior duodenal ulcer rutpure can lead to (2):
Acute pancreatitis; gastroduodenal artery bleeding
720
Which artery bleeds in a ruptured gastric ulcer?
Left gastric artery (lesser curvature)
721
2 subtypes of gastric AC & risk factors
Intestinal: large, irregular ulcer (lesser curvature of antrum) -- metaplasia, nitrosamines smoked foods, blood type A
Diffuse: signet ring/linitis plastica (desmoplasia: reactive stromal response); not associated with H.pylori, nitrosamines, blood type A
722
Intestinal gastric AC is associated with blood type
A
723
Acanthosis nigricans [axillary] or Leser-Trelat sign [dozens of subheroic keratoses] can be associated with which type of cancer?
Gastric AC
724
Left supravlavicular LAD
Gastric AC
725
Krukenburg tumor seen with which subtype of gastric AC?
Diffuse gastric AC
726
Sister Mary Josheph nodule seen with which subtype of gastric AC?
Intestinal gastric AC
727
Congenital failure of small bowel to canalize is associated with what syndrome?
Duodenal atresia; Down Syndrome
728
Double-bubble sign on AXR
Duodenal atresia (bilious vomiting); polyhydramnios
729
Meckel diverticulum is a true/false?
True; arises due to failure of vitelline duct to involute [nutrients]
730
Passing meconium thorough the umbilicus
Failure of vitelline duct to involute 100%
731
Rule of 2's
2% population, 2 inches long, 2 feet from IC valve; 2 y.o., bleeding/volvulus/intussuception/obstruction
732
Twisting of bowel along mesentary; classical locations in adult vs child
Volvulus (obstruction and infarction)
* Adult: sigmoid colon
* Child: cecum
733
Telescoping of proximal segment of bowel into distal. P/W currant jelly stools. Common causes in children and adults
Intussception; children = lymphoid hpyerplasia [ileum with many Peyer's patches]; adults = cancer
734
T/F Small bowel is susceptible to ischemic injury
True; p/w abdominal pain, bloody diarrhea, decreased bowel sounds
735
Marked hypotension can result in transmural or mucosal infacrction of small intestine?
Mucosal
736
HLA DQ2, DQ8 is associated with which small bowel disease?
Celiac disease
737
The role of tissue transglutaminase in celiac disease?
Deaminates glaidin
738
Dermatitis herpetiformis
IgA deposition at tips of dermal papillae; Celiac disease
739
Anti IgA Ab: endomysium, TTG, gliadin [can tests IgG in IgA deficiency patients]
Celiac disease
740
Flattening of villi, hyperplasia of crypts with epithelial lymphocytes
Celiac disease
741
Damage in celiac disease is typically in what part of the intestine?
Duodenum
742
Small bowel carcinoma and T cell carcinoma can present in patients with...
Celiac disease (refractory despite good dietary control)
743
Enteropathy associated T cell lymphoma
Celiac disease
744
Damage in tropical sprue is most prominent in what part of intestine?
J, I. (Duodenum in celiac disease)
745
Folate abosrbed
Jejunum
746
B12 absorbed
Ileum
747
PAS+ organisms in macrophage lysosomes of the gut
Whipple disease [LP of small bowel]
748
Whipple disease p/w
Arthritis, valves, LN, CNS; Fat malabsorption & steatorrhea (lots of macrophages in LP, can't bring in the chylomicrons)
749
Abetalipoproteinemia
B-48: chylomicron
| B-100: VLDL, LDL
750
Chromgranin+ means
Neuroendocrine tumor
751
Neuroendocrine tumor of the gut occurs in what part of the gut
Carcinoid tumor; small bowel
752
Once a carcinoid tumor mets to the liver, it creates a patient who p/w
Bronchospasm, flusing, diarrhea [carcinoid syndrome]
753
What are 2 triggering factors of carcinoid syndrome?
ETOH, Emotional stress
754
Appendicitis in child vs. adult is 2/2
Child: lymphoid hyperplasia
Adult: fecalith
755
Lead pipe sign vs. string sign on imaging
Lead pipe: UC
| String sign: Crohn's
756
Smoking UC vs. Crohn's
UC: protective
| Crohn's: increases risks
757
Crypt abscess on histology with pseudopolyps and loss of haustra
UC
758
P-ANCA is positive in what bowel disease?
?UC
759
Bloody diarrhea: UC or Crohn's
UC
760
Granulomas: UC or Crohn's
Crohn's
761
Cobblestoning: UC or Crohn's
Crohn's
762
Stricturing and creeping fat: UC or Crohn's
Crohn's
763
Malabsorption: UC or Crohn's
Crohn's
764
Lead pipe sign in UC 2/2
Loss of haustra
765
Hirschsprung disease is associated with what syndrome?
Down Syndrome
766
Down Syndrome: small and large bowel
Small: duodenal atresia
Large: Hirschsprung disease
767
Congenital failure of ganglion cells to descend [neural crest]
Hirschsprung disese
768
Meissner's vs.
| Aurebach's mysenteric plexus
Meissners: SM [blood flow, secretions]
| Auerbach's: peristalsis and relaxation
769
Rectal suction biopsy reveals a lack of ganglion cells in Hisrschprung disease because...
Must look at submucosa
770
Colonic diverticulum involves which layers?
Mucosa, Submucosa
771
Colonic diverticulum arises 2/2 in what location?
Wall stress, constipation, low fiber; where vasa recta traverse the muscularis propria -- weakened wall [sigmoid colon]
772
Air or stool in the urine
Recto-vesico fistula 2/2 diverticulitis
773
Hematochezia in an older adult in Right colon 2/2 acquired malformation of mucosal and submucosal capillary beds
Angiodysplasia
774
AD disorder resulting in thin-walled blood vessels in nasopharynx and GIT
Hereditary teleangiectasia
775
Ischemic damage to the colon, usually at the splenic flexure 2/2
Atherosclerosis of SMA; post-prandial pain and weight loss
776
T/F Hyperplastic polyp of L colon is benign with no malignant potential. Has a serrated appearance on BX.
True
777
T/F Adenomtous polyp is premalignant
True
778
Describe the sequence of colon cancer development.
APC--->K-ras-->p53/inc. COX
779
APC is on chromosome
5
780
What over-the-counter drug can actually protect against colon cancer?
Aspirin (COX expression at the terminal end of adenoma-carcinoma sequence along with p53 mutation)
781
> 2cm, sessile, villous adenomatous colon polpy: increased or decreased theoretical cancer risk
Increased [villous = villian]
782
AD or AR: FAP
AD: Ch. 5
783
FAP with fibromatosis and osteoma
Gardner's syndrome (retroperit + bone)
784
FAP with CNS tumors (medulloblastoma and glial tumor)
Turcot syndrome
785
Sporadic hamartomatous benign poly that arises in children <5 y.o.; usually presents as soliarty rectal polyp that prolapses and bleeds
Juvenile polyp [large numbers in stomach and colon raise cancer risk]
786
Hamartomatous polyps throughout the GIT with mucocutaneous hyperpigmentation on lips, oral mucosa and genital skin (AD)
Peutz-Jeghers Syndrome: increased risk for breast, colorectal and GYN cancer
787
2 pathways of colon cancer
1. Adenoma-carcinoma
| 2. MSI (MMR)
788
Inherited mutation in DNA MMR repair enzymes; increased risk for colorectal, ovarian and endometrial carcinoma (Colorectal arises de novo R-sided)
HNPCC
789
Decreased stool caliber, LLQ pain, blood-streaked: L or R colon ca
L
790
Fe-deficiency anemia, vague pain: L or R colon ca
R
791
Serum tumor marker for colon ca
CEA
792
Breast is embryologically derived from
Skin
793
Breast tissue can develop anywhere along
Milk line
794
All ducts and lobules are lined by:
Luminal cell layer and myoepithelial cell
795
T/F Breast tissue is hormone sensitive
T
796
Anatomically, the highest density of breast tissue
UOQ
797
Acute mastitis 2/2 breast feeding usually caused by..
S. aureus
798
Subareolar mass with nipple retraction; Highly dependent on vitamin A; squamous metaplasia in the breast seen in a smoker.
Periductal mastitis
799
Green-brown nipple discharge; inflammation of subareolar duct presents in multiparous post menopausal woman [plasma cells]
Mammary duct ectasia
800
Fat necrosis [calcifications and giant cells] of breast that shows up as calcification on mammography 2/2
Trauma
801
Cystic dilation of mammary ducts and/or terminal duct in a pre-menapausal woman (lumpy bumpy blue dome cyst)
Fibrocystic change
802
Fibrocystic change: fibrosis, cysts and apocrine metaplasia. Any risk of ca?
No!
803
Fibrocystic change: ductal hyperplasia & sclerosing adenosis. Any risk of ca?
Yes: 2x invasive carcinoma in either breast
804
Fibrocystic change: atypical hyperplasia. Any risk of ca?
Yes: 5x invasive carcinoma in either breast
805
Can sclerosing adenosis be calcified on mammography?
Yes
806
Benign breast growth that bleeds in a pre-menapausal woman. What cells do you see?
Intraductal papilloma; fibrovascular core see both epithelial cells and myoepithelial cells
807
How do you differentiate a benign intraductal papilloma from papillary carcinoma?
Ca: only one cell type [no myoepithelial cells] also in an older woman
808
Tumor of fibrous tissue and glands; well circumscribed "mouse in the breast" that is estrogen sensitive in a pre-menopausal woman
Fibroadenoma
809
Fibroadenoma-like tumor with overgrowth of fibrous component; leaf-like projections in post menopausal women
Phyllodes tumor
810
Major risk factor for breast cancer
Estrogen exposure
| * Female, age, early menarche/late menopause, obesity, atypical hyperplasia
811
DCIS that reaches the nipple
Paget's disease of the breast
812
Major types of breast cancer
DCIS, LCIS
813
What type of DCIS has high-grade cells with necrosis and dystrophic calcification in center of ducts?
Comedo type of DCIS
814
How is DCIS seen on mammography?
Calcification
815
3 potential pathologies of calcification on mammography?
1. Fat nex
2. Sclerosing adenosis
3. DCIS
816
Most common type of invasive carcinoma of breast that p/w breast mass detected by PE or mammography
Invasive ductal carcinoma
817
Duct-like structures in desmoplastic stroma of breast bx
Invasive ductal carcinoma
818
Subtypes of invasive ductal carcinoma
Tubular carcinoma
Mucinous carcinoma
Medullary carcinoma
Inflammatory carcinoma
819
Subtype of invasive ductal carcinoma with a good prognosis
Tubular carcinoma
820
Subtype of invasive ductal carcinoma with a good prognosis seen in elderly women
Mucinous carcinoma
821
Subtype of invasive ductal carcinoma that p/w an inflammed breast that does not resolve with ABX; bx cancer w/in dermal lymphatics
Inflammatory carcinoma
* Clincopathologic
* DDX acute mastitis
822
Subtype of invasive ductal carcinoma seen in pts with BRCA1 mutations
Medullary carcinoma
823
Underlying pathology in LCIS
Dyscohesive cells lacking e-cadherin
824
BRCA & E-cadherin
LCIS
825
Multifocal and B/L: DCIS or LCIS
LCIS
826
What type of breast cancer is often discovered incidentally?
LCIS [Tamoxifen and close follow-up]
827
Breast cancer that grows in single-file pattern?
E-cadherin / invasive lobular carcinoma
828
Most patients with BRCA don't p/w mets. Therefore, the most useful factor in prognosis is...
Spread to axillary LN
829
T/F Her2Neu is a cell surface receptor proto-oncogene.
T
830
Triple negative cancer: positive or negative PGX. What demographic of women?
Negative: AA women
831
BRCA1 or BRCA2: Breast cancer in males. What other syndrome?
BRCA2; Klinefelter syndrome
832
BRCA1 mutations associated with which 2 cancers?
Breast, ovarian *serous*
833
Highest density of breast tissue in a male
Sub-areolar
834
Males develop ductal or lobular carcinoma
Ductal (males don't develop lobules)
