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Step 1 Miscellanous > Pathoma High Yield Principles > Flashcards

Pathoma High Yield Principles Flashcards

1
Q

How is the cytoskeleton and organelles broken down during atrophy?

A

Cytoskeleton - tagged via ubiquination -> proteasome pathway

Organelles - via autophagy

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2
Q

Why is BPH a notable exception to pathologic hyperplasia?

A

It is one type of pathologic hyperplasia which does NOT increase risk for cancer
(i.e. vs endometrial hyperplasia)

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3
Q

What is keratomalacia? What causes it?

A

Disorder of the conjunctiva of the eye which causes it to thicken
-> due to loss of Vitamin A, which is required for differentiation of specialized epithelial surfaces

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4
Q

What cellular phenomena are streak ovary and unilateral renal agenesis examples of?

A

Streak ovary - hypoplasia (decreased cell production during embryogenesis)

Renal agenesis - aplasia - failure of cell production during embryogenesis

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5
Q

What is the definition of hypoxemia?

A

PaO2 < 60 mmHg, SaO2 <90% (hemoglobin saturation %)

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6
Q

How are PAO2 and PACO2 related?

A

As PACO2 goes up (i.e. hypoventilation, COPD), PAO2 must fall (crowding out O2 in the alveoli) -> results in hypoxemia and ultimately decreased SaO2

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7
Q

How does carbon monoxide affect PaO2 and SaO2?

A

PaO2 - normal

SaO2 - decreased (less oxygen bound since it is tightly binding CO)

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8
Q

What is the earliest symptom of carbon monoxide poisoning?

A

Headache

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9
Q

What are the causes of methemoglobinemia?

A
  1. Oxidant stress - i.e. nitrates, drugs like benzocaine (anesthetic)
  2. Newborns -> decreased ability to reduce iron back to Fe+2
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10
Q

What is the classic physical exam findings with methemoglobinemia and what is the treatment?

A

Cyanosis with chocolate-colored blood

Treatment - IV METhylene blue, Vitamin C

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11
Q

What happens to microvilli during reversible hypoxic injury?

A

Microvilli are lost -> like inflating a nitrile glove so you can’t differentiate between the fingers
-> due to cellular swelling

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12
Q

What happens to protein synthesis in reversible cellular injury and why?

A

It decreases, since ribosomes pop off of the ER which is swelling

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13
Q

In what type of tissue can red infarction occur?

A
  1. If blood can re-enter the tissue

2. The tissue must be loosely organized so blood, i.e. testicle or lung

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14
Q

Why does liquefactive necrosis occur in the brain?

A

Microglial cells liquefy the brain by release of hydrolytic enzymes

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15
Q

What type of necrosis happens in the parenchyma of the pancreas in acute pancreatitis?

A

Liquefactive necrosis -> digestive via proteolytic enzymes

Fat necrosis occurs in the surrounding fat. - peripancreatic fat

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16
Q

What is the most damaging free radical species and how is it generally produced?

A

Hydroxyl free radical -> because it can only be broken down by glutathione peroxidase

Generally produced via ionizing radiation

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17
Q

What is the underlying pathophys of damage in Wilson’s dz or Hemochromatosis?

A

Generation of free radicals -> cirrhosis

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18
Q

What causes Familial Mediterranean fever? What is the hallmark of the condition

A

Autosomal recessive mutation in pyrin, a regulator of pro-inflammatory cytokines. Leads to recurring fever, joint pains, and serositis with overproduction of IL-1 -> systemic accumulation of AA amyloid (SAA)
-> this is a neutrophil dysfunction disorder

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19
Q

What is the most commonly involved organ in amyloidosis? Other classical findings?

A

Kidney -> leads to nephrotic syndrome

Restrictive cardiomyopathy
Tongue enlargement
Hepatosplenomegaly, malabsorption

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20
Q

What amyloidopathies do normal vs mutated transthyretin cause?

A

Normal - Commonly an asymptomatic senile cardiac amyloidosis (common in elderly) - ATTR

Mutated - Familial amyloid polyneuropathy / cardiomyopathy - deposition of ATTR in peripheral nerves and in heart.

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21
Q

What are the three major factors which stimulate degranulation of mast cells (to release histamine)?

A
  1. Tissue trauma
  2. Complement proteins C3a / C5a
  3. IgE cross-linking
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22
Q

What is the immediate response to histamine? Late response?

A

Arteriolar vasodilation, postcapillary venule increased capillary permeability

Late response: Leukotriene synthesis and release (vasoconstriction, bronchospasm, increased vascular permeability)

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23
Q

What is the classical pathway? What pathway is most similar to it?

A

GM makes classic cars. Complement protein binds IgM or IgG

Other pathway most similar to it is Mannose-binding lectin (MBL) -> a lectin is a sugar-binding protein which binds mannose residues on microorganisms

The MBL acts as an antibody which triggers the cascade

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24
Q

What is the alternative pathway?

A

Microbial products directly activate complement

C3b directly binds to the pathogen and is stabilized by factor B and properdin to C3 convertase for further opsonization

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25
Q

What is the kinin system and how is it activated? What will Hageman factor do?

A

A system of plasma proteins which are activated in inflammation (much like complement)

Activated when Hageman factor (Factor 12) contacts collagen, which facilitates its conversion to 12a

12a will convert prekallikrein to kallikrein

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26
Q

What are the four functions of kallikrein?

A

Kallikrein - 4 functions

  1. Chemotactic agent like C5a or IL-8
  2. Converts HMW kininogen to bradykinin
  3. Converts plasminogen to plasmin
  4. Increases conversion of 12 (Hageman factor) to 12a (with HMWK as cofactor) -> positive feedback loop
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27
Q

What are the two main mediators of pain? How do they do this?

A
  1. Bradykinin
  2. Prostaglandin E2

They do this by sensitizing nerve endings

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28
Q

How is fever generated?

A

Macrophages release pyrogens IL-1 and TNF which travel to the hypothalamus and stimulate prostaglandin E2 synthesis which raises the setpoint of the hypothalamus

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29
Q

How does rolling occur? What upregulates this?

A

Leukocytes transiently attach to E-selectins on endothelium in a low affinity interaction to slow them down via their sialylated carbohydrate ligands (sialyl-Lewis) receptors.

E-selectins - upregulated by TNF / IL-1
P-selectins - upregulated via histamine, from Wiebel-Palade bodies

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30
Q

What mediates adhesion? What upregulates this?

A

Firm attachment, high affinity interaction between VCAM-1 and ICAM-1 (integrin ligands) of endothelial cells and ligands on leukocytes.

ICAM/VCAM are upregulated via IL-1 and TNF.
Ligands = Integrins. Upregulated by LTB4 and C5a, they neutrophil chemoattractant agents

ICAM = intercellular adhesion molecule

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31
Q

What is absent in LAD-1? What are the early features?

A

CD18 - an integrin receptor on leukocytes

Clinical features - delayed separation of the umbilical cord (requires necrosis), increased pool of circulating neutrophils (loss of tight binding as marginated pool of neutrophils), recurrent bacterial infections with lack of pus

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32
Q

What happens to neutrophils in Chediak-Higashi (CH) and why is this relevant? What’s the inheritance pattern? What is seen histologically?

A

Enlarged lysosomes with impaired neutrophil function -> poor phagolysosome formation and bactericidal activity
-> recurrent pyogenic infections. Also neutropenia since protein trafficking is required for cell division.

Autosomal recessive protein trafficking defect and phagolysosome formation.

Histologically - Giant granules from failure of trafficking = fusion together

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33
Q

What happens to skin, nerves, and hemostasis in CH?

A

Skin - pigment not properly trafficked in melanocytes - albinism

Nerves - periphery neuropathy - failure to traffick proteins to distal end of nerve

Hemostasis - defective primary hemostasis due to lack of dense core granule secretion

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34
Q

What are two tests for diagnosis of CGD?

A
  1. Dihydrorhodamine (DHR) flow cytometry test -> CGD neutrophils can’t oxidize DHR to fluoresce rhodamine
  2. Nitroblue tetrazolium (NBT) -> CGD neutrophils can’t turn yellow NBT to insoluble, blue-black NBT. Blue = intact.
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35
Q

What does myeloperoxidase deficiency cause? What will NBT test show?

A

Usually asymptomatic, but can cause an increased risk for candida infections.

NBT test will be normal since respiratory burst (NADPH oxidase) is intact

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36
Q

How do neutrophils resolve after doing their job?

A

They die by APOPTOSIS -> forming pus

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37
Q

How do macrophages normally do their killing? How do they continue inflammation?

A

Usually via oxygen-INDEPENDENT killing, i.e. lysozymes.

They can secrete IL-8 to continue inflammation

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38
Q

What are the two broad categories of macrophages? How are they activated and what is their function?

A

M1 - classically activated - via TH1 cells and IFN-y, function in inflammation and microbial killing

M2 - alternatively activated - via TH2 cells, release anti-inflammatory factors like IL-10 and TGF-beta, and stimulate fibrosis / tissue repair via growth factors.

Think IL-10 = atTENuating the immune response
-> also produced by Th2 cells to inhibit Th1 subset

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39
Q

What cytokines does the Th1 subset secrete and what does this do? What causes formation of this subset?

A

Secretes IFN-y -> activates macrophages, induces class switching to IgG3, suppresses Th2 response

Secretes IL-2 -> T cell growth factor and stimulator of CD8 cells (costimulator for cytotoxic cells which encounter their MHCI)

Induced by macrophages secreting IL-12

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40
Q

What cytokines does the Th2 subset secrete and what does this do? What causes formation of this subset?

A

Secretes IL-4, IL-5, IL-10 and IL-13

IL-4 - Class switching to IgE and IgG, inhibits Th1
IL-5 - Eosinophil chemotactic agent, class switching to IgA
IL-10 - Inhibits Th1
IL-13 - similar to IL-4

Induced by IL-4, IL-2 from APCs

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41
Q

What are the three ways to activate apoptosis?

A
  1. Intrinsic mitochondrial pathway - loss of Bcl2 due to cellular damage, DNA damage, or loss of growth factor stimulation
  2. Extrinsic pathway - mediated by Fas/FasL or TNFalpha
  3. Perforin and granzymes from CD8 cells -> activates intrinsic / extrinsic pathways
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42
Q

What are two broad ways B cells can be activated?

A
  1. Interaction between antigen and IgM molecules on surface -> continued secretion of IgM
  2. Expression of ligands on MHC II -> costimulation by CD4 cells via CD40L interacting with their CD40 receptor, and then class switching and antigen maturation induced by third signal (IFNy, IL-4, or IL-5)
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43
Q

What is the histologic hallmark of cat scratch disease? What is the defining feature of this whole finding?

A

Stellate-shaped granulomas

Defining feature of granulomas - epithelioid histiocytes with abundant pink cytoplasm.

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44
Q

What is the DDx of caseating granulomas?

A

TB and fungus

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45
Q

What is the DDx of noncaseating granulomas?

A
  1. Sarcoidosis
  2. Berylliosis
  3. Crohn’s disease
  4. Cat scratch disease
  5. Foreign body reaction
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46
Q

What infections are people with Ig deficiency more susceptible to?

A

Lack of IgA - Giardia and enteroviruses (i.e. polio / coxsackie virus)

Lack of IgG - bacterial infections, especially S. aureus, S. pneumoniae, H. influenzae

47
Q

What is common variable immunodeficiency (CVID)? How does it differ from the other similar condition?

A

The common variable is “hypogammaglobulinemia”

  • > group of heterogeneous disorders which decrease Ig’s sometimes only IgG.
  • > differs from Bruton’s because it is autosomal recessive and not X-linked

(seen in girls now)
-> also tends to be diagnosed much later than Bruton’s, in teenage years

48
Q

For common variable immunodeficiency, is a B-cell deficit always present? What is it normally? How could it not be present?

A

Normally a defect to differentiate into plasma cells to produce antibody

B cell deficit does NOT need to be present -> can just be T-cell disorder with excessive immunosuppression or failure to help develop Abs.

-> nodular hyperplasia which results predisposes to autoimmune disease and lymphoma

49
Q

What disorders are associated with CVID, and what is the treatment? How is this similar to XLA (Bruton’s)?

A

Autoimmune disorders like RA, and B-cell lymphomas

-> treatment: periodic IV immunoglobulin (same as XLA)

XLA also predisposes to autoimmune disorders due to defect BTK signalling -> required for destroying self-reactive B cells

50
Q

What is the most common primary immunodeficiency? How do you get it?

A

Selective IgA deficiency

Can be congenital or acquired (toxoplasmosis, viral infections, drug exposures

51
Q

What is one important consideration when treating someone with selective IgA deficiency?

A

~40% will have serum antibodies to IgA

  • Most are IgG and would just cause serum sickness, but some have IgE which can cause anaphylaxis
52
Q

What disorders are associated with selective IgA deficiency?

A

Increased respiratory allergies, autoimmune diseases like RA / SLE, and CELIAC DISEASE

53
Q

What causes Hyper IgM syndrome and what lab values will be associated? What is the mode of inheritence?

A 
X-linked
Defect in CD40L required for class switching

Associated with normal or high IgM, and low IgA, IgG, and IgE (AGE)

54
Q

What causes Wiskott-Aldrich Syndrome? Inheritance pattern?

A

Mutation in WASp, which functions in reorganizing cytoskeletal actin.

This is required for B cell, T cell, and platelet function

Pattern of inheritance: X-linked

55
Q

Early on, what type of infection are Wiskott-Aldrich patients susceptible to? What poses their greatest risk of death?

A

Susceptible to encapsulated pyogenic bacterial infection (poor polysaccharide antibody response, peptide is okay). This is because IgG is normal but IgM is low -> IgM important for complement activation and polysaccharide response (increased S. pneumoniae infections)/

-> Bleeding risk due to low, small platelet count risks death

56
Q

What selection takes place during the double positive stage (stage 2)? This follows the double negative stage where TCR rearrangement occurs and both CD4 / CD8 become expressed.

A

Positive selection - T cells bind with weak affinity to self MHC
Negative selection - T cell binding is too strong - recognition of self = apoptosis
Death by neglect - unreactive T cells to MHC die via apoptosis after neglect.

-> MHC type which they have the best affinity for determines if they will become CD4 or CD8 cell (other receptor is downregulated).

57
Q

What is the triad of AIRE loss / autoimmune polyendocrine syndrome?

A

APS-1:

  1. Autoimmune adrenalitis - Addison’s
  2. Autoimmune parathyroiditis - hypoparathyroidism
  3. Recurrent candida infections - Chronic mucocutaneous candidiasis
58
Q

What do V, D, J, and C stand for? Which are not present in light chains? What is the order of light chain rearrangement?

A 
V = variable
D = diversity
J = joining
C = constant

Diversity segments are not present in light chains

Kappa rearranges before lamda, thus normal Kappa to Lamda ratio is 3:1

59
Q

What is receptor editing?

A

A second chance that B cells have (versus apoptosis or anergy) to not express Ab self-antigen.

Occurs via additional rearrangement of LIGHT CHAIN which changes the Ab specificity of cell.

Failure results in apoptosis / deletion

60
Q

What is clonal anergy? How can this be reversed?

A

When cells are unresponsive but not deleted. Can be reversed via IL-2, which upregulates CD28

61
Q

What are the mechanisms of peripheral tolerance? Where does it happen?

A

Taking place in secondary lymphoid organs

  1. Clonal deletion
  2. Clonal anergy
62
Q

How does clonal deletion occur?

A

3 ways:

  1. Activation-induced cell death
  2. Superantigens (1/2 are very similar)
  3. Apoptosis via Fas-FasL interaction
    - >
63
Q

How do cells become anergized?

A

Cells receive TCR stimulation without costimulation via CD28/B7
-> basically like APCs are presenting antigen without the costimulation signal, indicating that this is not an antigen they should be binding

64
Q

How does activation-induced cell death of T-cells occur?

A

Initially, T-cells are resistant to Fas-mediated apoptosis. However, as they become overactive, they will T cells will overexpress Fas / FasL, allowing for paracrine / autocrine deletion via apoptosis.

Furthermore, overtime they increase expression of CTLA4, which, if bound by B7, is an inhibitory signal (the antagonist to CD28)

65
Q

What is defective in autoimmune lymphoproliferative syndrome (ALPS)?

A

Fas-FasL pathway - see pg. 204
-> high proportion of self-reactive lymphocytes
Usually a mutation of Fas
-> lymphadenopathy / hepatosplenomegaly / autoreactive IgG, increased risk of Lymphoma

66
Q

What is the function of Treg cells and what cytokines do they produce?

A

Suppress activation of immune response via production of TGFb and/or IL-10

They also express CTLA4 and bind B7, preventing the interaction betwen CD28 and B7 on CD4 cells.

67
Q

What are natural Tregs?

A

Cells generated in thymus based on intermediate affinity for self-MHC. Upregulate the Foxp3 transcription factor, and highly express CD4 and CD25 (beta chain of IL-2 receptor)

68
Q

What are CD25 polymorphisms associated with?

A

Autoimmunity - i.e. MS and Type 1 diabetes

69
Q

What syndrome does Foxp3 mutation cause? Symptoms?

A 
IPEX
Immune dysregulation,
Polyendocrinopathy - thyroiditis and pancreatitis -> destruction of pancreatic islets
Enteropathy - diarrhea
X-linked - (diabetes in males infants)

Also has dermatologic manifestations i.e. dermatitis / nail dystrophy

70
Q

What is autoimmune disease more common in women of childbearing age?

A

Estrogen is thought to inhibit the apoptosis of autoimmune B cells
-> explains why when lupus occurs in young children and older adults, the female bias is less dramatic

71
Q

What is PTPN22 mutation associated with?

A

It is a tyrosine phosphatase. Loss is associated with the development of autoimmune disease since signalling is required for anergy -> implicated in RA
-> like HLA-B27 is associated with autoimmune disease

72
Q

Why does early complement deficiency predispose to lupus?

A

Early complement components are requires for clearing antigen-antibody complexes

If they are not cleared, they can be taken up by dendritic cells and activate TLRs, amplifying immune response, as well as be deposited in tissues.

The CR1 receptor exists on RBCs and is a C4b/C3b receptor to mediate uptake of antibodies

73
Q

Which lupus antibody is most associated with prognosis as well as active disease?

A

Anti-dsDNA

-> amount of antibody present can be used to guide treatment

74
Q

What antibodies are associated with antiphospholipid syndrome? Which one interferes with VDRL / RPR testing?

A
  1. Lupus anticoagulant - this one falsely elevates the aPTT (instrinsic)
  2. Anticardiolipin antibody - this one interferes with VDRL
  3. Anti-Beta2 glycoprotein (an apolipoprotein).

These are all pro-thrombotic

75
Q

What is the definition of antiphospholipid syndrome (APS)? Does it always happen in lupus?

A

Arterial or venous thrombosis or recurrent miscarriage in association with evidence of persistent antiphospholipid antibodies. Remember this is the #2 cause of Budd-Chiari syndrome.

Often arises in the setting of another CT disorder i.e. Lupus or systemic sclerosis, called secondary APS

**PRIMARY APS also occurs more commonly, not associated with anything else

76
Q

What are the typical causes of death in late-stage lupus?

A

Renal failure, infection (due to immunosuppressive therapy), or accelerated coronary artery atherosclerosis
-> alot like diabetes in the fact that atherosclerosis is scary

77
Q

What is Sjogren syndrome and its two forms? What is the secondary form commonly associated with?

A

Chronic autoimmune disorder of lacrimal and salivary glands, common in middle-aged women

Primary - sicca syndrome (dry eyes -keratoconjunctivitis sicca / mouth - xerostomia)

Secondary - associated with another immune disease -> especially rheumatoid arthritis

78
Q

What are antibodies typically direct against in Sjogren syndrome? What will the salivary glands show?

A

Rheumatoid factor (especially in secondary) and ribonucleoproteins (protein + RNA) SS-A (Ro) and SS-B (La)

Salivary gland - lymphocytic sialadenitis on minor salivary gland (lip) biopsy

79
Q

What is neonatal lupus? What antibodies are associated with? What problem does it cause?

A

Congenital condition associated with anti-SS-A (Ro) or anti SS-B (La) antibodies from the mother that affect the fetus.

Can cause heart block of varying degrees in utero (congenital heart block)

Obviously can also occur in Sjogren syndrome.

80
Q

What are two other causes of dry eyes / dry mouth which aren’t Sjogren’s syndrome?

A
  1. Amyloidosis gland destruction
  2. Sarciodosis
  3. Drugs (i.e. anticholinergics)
  4. Prior radiation
81
Q

What should you be concerned about if you have unilateral enlargement of the parotid gland late in the disease course of Sjogren syndrome?

A

Marginal zone B cell lymphoma (similar to Hashimoto’s, from B cell proliferation).

82
Q

What is the underlying pathogenesis of systemic sclerosis?

A

Autoimmune activation -> endothelial dysfunction leads to increased expression of adhesion molecules (brings immune cells into interstitium) and secretion of cytokines including endothelin and decreased NO which induces vasoconstriction.

Progressive vasoconstriction as well as activation of T cells and macrophages which activate fibroblasts via TGF-beta and PDGF, causes progressive fibrosis and worsening ischemia -> further fibrosis

83
Q

What is localized vs systemic scleroderma?

A

Localized - limited to the skin only. Only causes the superficial skin manifestations

Systemic - includes diffuse and limited (i.e. CREST), and is the major subject of concern. This means it affects the skin as well as the internal organs.

84
Q

What is the major cause of death in diffuse systemic sclerosis and which organ is most COMMONLY affected?

A

Most common - GI tract involvement - esophageal dysmotility and GERD

Cause of death: #1 - scleroderma renal crisis
#2 - pulmonary hypertension and fibrosis
85
Q

What antibody is associated with diffuse scleroderma? Limited?

A

Anti-Scl-70, think scleroderma-70

This is an anti-DNA-topoisomerase I antibody.

Limited - anti-Centromere -> CREST

86
Q

What are the features of scleroderma renal crisis (important)? When does it occur? Best way to reduce mortality?

A

Accelerated hypertension (>150/90) and oliguric acute renal failure

  • > fibrosis leads to activation of the renin-angiotensin aldosterone system
  • > Leads to hypertensive crisis and congestive heart failure with pulmonary edema
  • > occurs in the first few years of diffuse systemic sclerosis

best way to reduce mortality is an ACE inhibitor for obvious reasons -> RAA mediated.

87
Q

Features of what diseases overlap in mixed connective tissue disease? What antibody characterizes it? Pattern on IF?

A
  1. SLE
  2. Systemic sclerosis
  3. Polymyositis / dermatomyositis

Characterized by anti-U1 RNP antibodies (speckled pattern on IF)

88
Q

What is regeneration vs repair?

A

Regeneration - replacement of damaged tissue with native tissue - labile / stable tissues. Except when the damage is best enough that the stem cells are lost -> repair.

Repair - replacement via scar tissue - especially permanent tissues

89
Q

What are the markers for hematopoietic stem cells?

A

CD34 and CD117

90
Q

What are labile / stable tissues?

A

Labile - i.e. GI tract, skin, ready to divide at any time

Stable - Sit in G0 phase but can be reactivated - i.e. proximal tubule cells of kidney, hepatocytes

91
Q

What is the original type of collagen present in granulation tissue and how must it be replaced?

A

Type III collagen produced by fibroblasts -> very pliable and stretchy which is needed. Must be replaced by a collagenase which requires ZINC as a cofactor (metalloprotease).

WIll be replaced by Type I collagen.

92
Q

What is FGF important for?

A

Angiogenesis, as well as skeletal development

  • > secreted in granulation tissue for angiogenesis
  • > secreted by apical ectodermal ridge to induce underlying mesenchyme
93
Q

What collagen type is found in hypertrophic scars and keloids?

A

Hypertrophic scars - excess Type I collagen

Keloid - massive scar overgrowth, actually made of Type III collagen!!! Type 3!!!

94
Q

What is the historical way in which monoclonality over tumor cells was shown in women?

A

Loss of 1:1 ratio of the two inherited isoforms of G6PD in monoclonal proliferations, since the same Barr body is always inactivated in progeny of cells, and this is all one cell type.

95
Q

How will the ratio of kappa to lambda change in lymphoma vs infection?

A

Normal 3:1

Kappa:Lambda > 6:1, or inverted (e.g. Kappa:Lambda 1:3)
-> All monoclonal cells will express the same light chain.

Infection: Reactive hyperplasia -> remains 3:1 since polyclonal

96
Q

What is a benign tumor of lymphocytes called?

A

Does not exist. Always malignant.

Tumors are by definition clonal neoplasms so infection wouldn’t count for this.

97
Q

Roughly how many divisions of cancer must occur before the earliest clinical symptoms arise?

A

About 30. But some are detected super late, i.e. ovarian carcinoma, lung, pancreas.

The more they divide -> more mutations -> poor prognosis.

98
Q

What cancers does Arsenic predispose to?

A
  1. Squamous cell carcinoma of the skin -> since it induces hyperkeratosis
  2. Lung cancer - since arsenic is present in cigarette smoke
99
Q

What cancers are nitrosamines associated with?

A

Intestinal type of stomach carcinoma -> smoked foods in Japan

100
Q

What is naphthylamine associated with? Where does it come from?

A

Urothelial carcinoma of the bladder

Present in rubber and dye industries, also derived from cigarette smoke -> explains the propensity of smoking to cause renal and bladder cancer (note that most of these carcinogens are polycyclic hydrocarbons)

101
Q

Major risk factor of angiosarcoma of the liver?

A

Vinyl chloride

102
Q

What are nickel, chromium, beryllium, or silica related to?

A

Occuputational exposures -> lung carcinoma

103
Q

What three cancers is ionizing radiation a risk factor for? Mechanism?

A

AML, CML, and papillary carcinoma of the thyroid

-> generation of hydroxyl free radicals which breaks double-stranded DNA

104
Q

What is a common autocrine loop which drives astrocytomas?

A

Platelet-derived growth factor (PDGF)

105
Q

What is the cell of origin of gastrointestinal stromal tumors, and what is the mutation of interest?

A

Interstitial cells of Cajal, within the wall of the intestine

Mutation of interest -> c-KIT, a growth factor receptor

106
Q

What does myc do and what three cancers are the three subtypes associated with?

A

C-myc - BurCitt lymphoma
N-myc - Neuroblastoma
L-myc - Lung carcinoma (small cell) - since aggressive

107
Q

What is the region closest to the follicle in B cells which can become cancerous and what mutation is assocatied it?

A

Mantle

Mantle cell lymphoma: 11;14 translocation -> cyclin D over-expression

108
Q

What is the mechanism by which p53 induces apoptosis if DNA damage is too bad to repair?

A

It recruits BAX and BAK, which destroy Bcl-2.

Bcl-2 is responsible for stabilizing the inner mitochondrial membrane so that cytochrome c (involved in oxidative respiration) cannot leak out and initiate the intrinsic pathway of apoptosis

109
Q

Why is the fact that apoptosis cannot occur in follicular lymphoma a problem?

A

Well, normally its not an issue if cells don’t undergo apoptosis. But in the lymph node where we have somatic hypermutation going on, we want to be able to induce apoptosis in the useless B cell lines which have failed their exam to produce an antibody which binds the antigen with higher affinity.

110
Q

Why does immunodeficiency lead to increased risk of malignancy?

A

CD8 T cells are required for killing cells which express abnormal tumor proteins on their MHC Class I -> can prevent tumor progression

111
Q

What is the critical sequence of events for tumorigenesis?

A
  1. Downregulation of E-cadherin
  2. Attachment to laminin in basement membrane
  3. Degradation of collagen IV in basement membrane via collagenase (metalloprotease #1084)
  4. Attachment to fibronectin and local spread
  5. Entrance into vascular / lymphatic spaces
112
Q

What are the four carcinomas which spread hematogenously?

A
  1. Renal cell carcinoma -> renal vein
  2. Follicular carcinoma of the thyroid
  3. Hepatocellular carcinoma -> hepatic vein
  4. Choriocarcinoma
113
Q

What is the absolute distinction between benign and malignant tumors? What is needed for definitive diagnosis of cancer?

A

Benign tumors NEVER metastasize

For diagnosis -> biopsy. Need to have a pathologist look at it.

114
Q

What are the components of the TNM system and which two are most important?

A

T - Tumor size or depth of invasion
N - pattern of spread to region lymph Nodes - second most important
M - Metastasis; presence of absence of distal metastasis. Most important

Step 1 Miscellanous (40 decks)

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