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Flashcards in Pathology Deck (834):
1

The exception to the rule that pathologic hyperplasia can lead to dysplasia cancer.

BPH: benign prostatic hyperplasia

2

Major cellular mechanism of cellular hypertrophy

Protein synthesis, gene activation and production of organelles (cytoskeleton, mitochondria)

3

Permnent tissues cannot undergo hyperplasia or hypertrophy. What are the 3 examples of permanent tissue in the body?

Hyperplasia
1. Cardiac muscle
2. Skeletal muscle
3. Nerve

4

Classical example of pathologic hyperplasia leading to dysplasia and cancer (female)

Endometrial hyperplasia

5

Mechanism of atrophy (2)

1. Apoptosis (decrease number of cells)
2. Ubiqiquitin-proteasome degradation of cytoskeleton; autophagy (cell size)

6

Metaplasia most often involves what body surfaces

Surface epithelium

7

Classical example of metaplasia (GIT)

Barret's esophagus (squamous--> columnar w/ goblet cells)

8

What is the mechanism of metaplasia? Is it reversible?

Reprogramming of stem cells; yes

9

What is the exception to the rule that metaplasia can progress to dysplasia and cancer (female).

Apocrine metaplasia (Fibrocystic change of the breast)

10

Deficiency of what vitamin can lead to metaplasia, i.e. keratomalacia?

Vitamin A: keratomalacia

11

t(15, 17) translocation

APML (cells trapped in blast)
* Treatment with ATRA

12

Mesenchymal tissues can undergo metaplasia. The classical example is:

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

How do you differentiate between osteosarcoma and myositis ossificans on an X-ray?

OS: part of bone
MO: distinct separation of bone from muscle

14

3 uses of vitamin A in the body

1. Night blindness
2. Immuno cells
3. Specialized epithelium

15

T/F Dysplasia is reversible

True

16

Aplasia; classical example

Failure of cellular production during embryogenesis

17

Hypoplasia; classical example

Decrease in cell production during embryogenesis
(Streak ovary in Turner Syndrome)

18

Cell injury occurs when stress ___________

Exceeds a cell's ability to adapt; type of stress, severity, type of cell affected

19

Slow progressive decrease in blood supply to the kidney results in _________; whereas a rapid decrease in blood supply results in _______

1. Atrophy
2. Infarction

20

T/F Neurons are very susceptible to hypoxia.

True

21

Common causes of cellular injury

Inflammation, nutritional deficiency/excess, hypoxia, trauma, genetic mutations

22

Define hypoxia

Low oxygen delivery to tissue; low ATP; cellular injury

23

The 3 major causes of hypoxia

1. Ischemia
2. Hypoxemia
3. Decreased O2 carrying capacity of the blood

24

Define ischemia. Through what 3 mechanisms can ischemia occur?

Decreased blood flow through an organ;
1. Arterial flow blockage (atherosclerosis)
2. venous outflow obstruction
3. 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)