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142 Cards in this Set

  • Front
  • Back
Pathologic hyperplasia can progress to dysplasia and cancer. What's the exception?
BPH
What degrades the cytoskeleton in atrophy?
Ubiquitin-proteosome
Metaplasia of Barret esophagus leads to change of nonkeratinized squamous epithelium to what?
nonciliated, mucin-producing columnar cells
Under persistent stress, metaplasia can progress to dysplasia and cancer. What is the exception?
Apocrine metaplasia of the breast (occurs during pregnancy)
Keratomalacia is an example of what type of growth adaptation?

It can be caused by deficiency of what?
Metaplasia (thin squamous lining -> stratified, keratinized squamous)

Vitamin A -> necessary for differentiation of specialized epithelial surfaces such as conjunctiva of eye
CIN is an example of what growth adaptation?
Dysplasia

(CIN = cervical intraepithelial neoplasia)
What growth adaption is a/w Turner Syndrome?
Hypoplasia (streak ovary)
Cyanosis w/ chocolate colored blood
Methemoglobinemia

"Fe2 binds O2"

iron is oxidized to Fe3+
Methemoglobinemia is seen with what?
oxidant stress (sulfa and nitrate drugs) or in newborns
What is the tx for methemoglobinemia?
IV methylene blue -> reduces Fe3+ back to Fe2+
Names for nuclear:

a) condensation
b) fragmentation
c) dissolution
a) pyknosis ("ink dot")
b) karyorrhexis
c) karyolysis
Psaomomma bodies are example of what?
dystrophic calcification

(saponification, a/w fat necrosis)
bright pink staining of vessel wall can indicate what?
fibrinoid necrosis
what stimulates intrinsic mitochondrial pathway of caspase activation?
lack of Bcl2 allows cytochrome C to leak from inner mitochondrial matrix
What are 2 examples of extrinsic receptor-ligand pathway of caspase activation?
1. FAS ligand binds FAS death receptor (CD95) on target cell (neg selection of T cells)

2. TNF binds TNF receptor on target cell
How do CD8+ T cells activate caspases?
Secrete perforins - create pored

Secrete granzyme - enters pores and activates caspases
Wilson's disease generates free radicals via...
increased copper
What is Fenton reaction?
iron generates hydroxyl free radicals
Enzymes for each step.

a) O2 -> O2* (superoxide)
b) O2* -> H2O2
c) H2O2 -> OH (hydroxyl free radical)
d) OH -> H20
a) NADPH oxidase
b) SOD (superoxide dismutase)
c) Glutathione peroxidase
d) Catalase
What is converted to free radical by p450 system, causes cell swelling (injury), impairs protein synthesis (ie: apolipoproteins) and causes fatty change in the liver?
CCl4

(organic solvent in dry-cleaning industry)
Histologic hallmarks of amyloid:
congo red staining and apple-green birefringence

also beta-pleated sheets
a) Primary amyloidosis is deposition of what (and derived from what)?

b) Secondary amyloidosis?
a) AL amyloid (Ig light chain)

b) AA amyloid (serum amyloid-associated protein SAA)
Examples of:

a) Primary amyloidosis

b) Secondary amyloidosis
a) plasma cell dyscrasias (ie: multiple myeloma)

b) chronic inflammatory states, malignancy, Familial Mediterranean Fever (FMF)

FMF: dysfx of neuts, AR, fever and acute serosal inflammation, high SAA during attacks deposit as AA
Non-mutated serum transthyretin a/w:
Senile cardiac amyloidosis
Mutated serum transthyretin a/w:
Familial amyloid cardiomyopathy
Amylin deposits a/w:
Non-insulin-dependent diabetis mellitus (type II)

amylin derived from insulin
a) A-beta amyloid (derived from beta-amyloid precursor Protein beta-APP) a/w:

b) Gene for beta-APP is on what chromosome?
a) Alzheimer's dz

b) 21 (a/w Down syndrome)
Beta2-microglobulin (structural component of MHCII) in joints a/w:
Dialysis-associated amyloidosis
Calcitonin deposits ("tumor cells in amyloid background") a/w:
Medullary carcinoma of thyroid

C-cells
TLRs...

a) are present on what?
b) are activated by what?
c) activation results in what?
a) cells of innate immunity (macrophages & dendritic cells) and adaptive immunity (lymphocytes)
b) PAMPs on microbes
c) upregulation of NF-kappaB (nuclear transcription factor; activates immune response genes -> prodn of immune mediators)
TLR that recognized LPS (a PAMP) on outer membrane of gram neg bacteria?
CD14 on macrophages
AA metabolites released from phospholipid cell membrane by what? then acted upon by one of what 2 things?
phospholipase A2

COX (PGs) or 5-lipoxygenase (LTs)
Overall, LTC4, LTD4, and LTE4 do what?
Contract SM!

(vasoconstriction, bronchospasm, increased vascular permeability)
3 ways to activate mast cells:
1. tissue trauma
2. C3a and C5a
3. cross-linking of cell-surface IgE by Ag
3 possible activations of complement cascade?
1. Classical pathway (C1 binds IgG or IgM bound to antigen; "GM makes classic cars")

2. Alternative pathway (microbial products directly activate complement)

3. MBL pathway (binds mannose on microorganisms)
Purpose of each:

a) C5a
b) C3a
c) MAC
a) chemotactic for neutrophils
b) opsonin
c) lyses microbes by creating hole in cell membrane
Name the inactive proinflammatory protein produced in liver, that becomes activated upon exposure to subendothelial or tissue collagen -> activates coagulation and fibrinolytic systems, complement, and Kinin system (cleaves HMWK to bradykinin -> histamine effects + pain)
Hageman factor (Factor XII)
Fever mechanism:

Pyrogens (LPS from bacteria) cause macrophages to release ____ and ____, which increase ____ activity in perivascular cells of hypothalamus. Leads to increase in _____, raising temp set point.
IL-1 and TNF; COX; PGE2
P-selectin is released from what and mediated by what?
Weibel-Palade bodies, mediated by histamine

(W for von willebrand factor, P for P-selectin)
E-selectin is induced by what?
TNF and IL-1

(just memorize)
Selectins on endothelium bind what on leukocytes?
Sialyl Lewis X
a) CAMs (ICAM and VCAM) are upregulated on endothelium by:

b) Integrins are upregulated on leukocytes by:
a) TNF and IL-1

b) C5a and LTB4
Leukocyte adhesion deficiency is most commonly due to AR defect of integrins, which subunit?
CD18 subunit
Neutrophils are attracted by what 4 things?
Bacterial products, IL-8, C5a, and LTB4
Chediak-Higashi is an AR defect in what?
protein trafficking (railroad defect) -> impaired phagolysosome formation
Chronic granulomatous disease (CGD) is AR or x-linked dz caused by a defect in what?

What is a screening test for CGD?
NADPH oxidase defect

NBT (turns blue if normal, colorless if defective)
MPO deficiency is a/w what infections?
Candida (however, most patients asymptomatic)
Examples of O2-independent killing from enzymes in leukocyte secondary granules:
lysozymes in macrophages and major basic protein in eosinophils
Macrophages can induce the following after acute inflammation via what mediators?

a) resolution/healing
b) continue acute inflammation
c) abscess
d) chronic inflammation
a) IL-10 and TGF-beta (anti-inflammatory)
b) IL-8 (recruits more neuts)
c) fibrogenic growth factors and cytokines
d) present Ag to CD4+ T cells
What is 2nd activation signal for:

a) CD4+ T cells?
b) CD8+ T cells?
a) B7 on APC binds CD28 on CD4+ (28/4 = 7)

b) IL-2 from CD4+ Th1 cell
Th1 cells secrete:
IL-2 (T cell growth factor, CD8+ T cell activator)

IFN-gamma (macrophage activator)
Th2 cells secrete:
IL-4 (B cell class switch to IgG and IgE)

IL-5 (eosinophil chemotaxis and activation, maturation of B cells to plasma cells, class switching to IgA)

IL-10 (inhibits Th1 phenotype)
CD40 receptor on ______ binds CD40L on ______, providing 2nd activation signal for _______.
B cell; helper T cell; B cell
a) Noncaseating granulomas a/w what diseases?

b) Caseating granulomas a/w what diseases?
a) foreign material, sarcoidosis, beryllium exposure, Crohn's disease, cat scratch disease

b) TB and fungal infections
In granuloma formation, what do macrophages secrete to induce CD4+ helper T cells to become Th1?
IL-12
DiGeorge syndrome: what is mutation?
22q11 microdeletion; developmental failure of 3rd and 4th pharyngeal pouches
3 etiologies for SCID:
1. cytokine receptor defects
2. ADA deficiency -> buildup of adenosine and deoxyadenosine is toxic to lymphocytes
3. MHCII deficiency
Mutation in X-linked Agammaglobulinemia?
mutate Bruton tyrosine kinase (BTK)

presents w/ bacterial, enterovirus, Giardia (d/t IgA)
What disorder is a/w low Ig due to B cell or helper T cell defects?
CVID

higher risk for bacterial, enterovirus, giardia, late childhood

a/w autoimmune dz and lymphoma
Celiac dz is a/w deficiency of what Ig?
IgA

most common Ig deficiency; mucosal infections, especially viral
Mutation in Hyper-IgM syndrome?
Mutated CD40L or CD40 receptor

low IgA, IgG, IgE, recurrent pyogenic infections, mucosal sites
What x-linked dz is a/w thrombocytopenia, eczema, and recurrent infections and is caused by a mutation in the WASP gene?
Wiskott-Aldrich Syndrome
C5-C9 deficiencies a/w increased risk of what infections?
Neisseria
Hereditary angioedema is caused by what?
C1 inhibitor deficiency
Libman-Sacks is a classic finding in what dz? What is it?
SLE; small, sterile deposits on both sides of mitral valve (instead of just one side)
In SLE, ____ is sensitive but not specific, while ______ is highly specific.
ANA antibody; anti-dsDNA antibodies
a) Antiphospholipid antibody syndrome is a/w what dz?

b) What are the 2 most common antibodies and what do they cause in labs?
a) SLE

b) anticardiolipin (false-positive syphilis) and lupus anticoagulant (falsely-elevated PTT)
Autoimmune destruction of lacrimal and salivary glands is what dz?
Sjogren Syndrome

type 4 hs w/ fibrosis

"can't chew a cracker, dirt in my eyes"
Anti-ribonucleoprotein antibodies are key feature of what disease?
Sjogren's syndrome

anti-SS-A/Ro and anti-SS-B/La
*target of SS-A and SS-B is ribonucleoprotein
Sjogren syndrome is especially a/w increased risk of what

a) autoimmune dz?
b) cancer?
a) RA
b) B cell (marginal zone) lymphoma, presents as UNILATERAL enlargement of parotid late in dz
Autoimmune disease with activation of fibroblasts and deposition of collagen (fibrosis):
Scleroderma
Anti-DNA topoisomerase (Scl-70) antibody is seen in what dz?
Diffuse type Scleroderma

(esophagus commonly affected, but any organ)
CREST syndrome? A/w what and what is it?
Localized scleroderma

Calcinosis/antiCentromere antibodies
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasias of skin
Mixed connective tissue disease has mixed features of what?

Characterized by what antibodies??
SLE, systemic sclerosis, polymyositis

*U1 ribonucleoprotein
U1 ribonucleoprotein antibodies are a/w what dz?
Mixed connective tissue disease
What is a cofactor for collagenase (removes type III collagen and replaces with type I in granulation tissue)?
ZINC
Fibroblast growth factor is important for what?
Angiogenesis! also skeletal development

Seen in tissue regeneration/repair
Mediators in tissue regeneration/repair:
TGF-alpha, TGF-beta, platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor (VEGF)
What is an important cofactor in hydroxylation of proline and lysine procollagen residues? (hydroxylation necessary for cross-linking)
Vitamin C
What is a cofactor for lysyl oxidase? (cross-links lysine and hydroxylysin in stable collagen)
Copper
What is dehiscence?
rupture of a wound; most common after abdominal surgery
Keloids have an excess amount of what type of collagen?
type 3 collagen
How can you determine clonality in a female's tumor?
G6PD enzyme isoforms (should be 1:1)

(also can use androgen receptor isoforms)
How can you determine clonality of an enlarged lymph node?
Ig light chain isoforms (kappa to lambda should be 3:1)
Approximately how many divisions occur before cancer produces its earliest clinical symptoms?
30
What does each of the following detect?

a) PAP smear
b) Mammography
c) PSA and DRE
d) Hemoccult test and colonscopy
a) cervical dysplasia (CIN) before carcinoma
b) in situ breast cancer (ex: DCIS calcifications in ducts) or carcinoma before palpable (clinical: 2 cm, xray: 1 cm)
c) prostate carcinoma before spread
d) colonic adenoma before carcinoma or carcinoma before spreads (remove adenomas!)
What cancer is a/w aflatoxins?
Hepatocellular carcinoma

Aflatoxin is derived from Aspergillus, which can contaminate stored grains. This cancer is very common in parts of Africa.
What cancers are a/w alkylating agents?
Leukemia/lymphoma

(side effect of chemo, years later)
What cancers are a/w alcohol?
Squamous cell carcinoma of oropharynx and upper esophagus, pancreatic carcinoma (via chronic pancreatitis), hepatocellular carcinoma (via cirrhosis)
What cancers are a/w arsenic?
squamous cell carcinoma of skin, lung cancer, angiosarcoma of liver

Arsenic is present in CIGARETTE smoke. Also, women used to put it on their skin to make their skin lighter, so people wouldn't know they were working -> caused skin cancer.
What cancers are a/w asbestos?
Lung carcinoma and mesothelioma

Lung is much more likely
What cancers are a/w cigarette smoke?
Carcinoma of oropharynx, esophagus, lung
kidney and bladder (carcinogens concentrate in urine and bathe the urothelium, not good!)

Polycyclic hydrocarbons are particularly carcinogenic
What cancer is a/w nitrosamines?
Stomach carcinoma (intestinal type)

High incidence in Japan b/c nitrosamines are found in smoked foods
What cancer is a/w naphthylamine?
Urothelial carcinoma of bladder

Derived from CIGARETTE smoke
What cancer is a/w vinyl chloride?
Angiosarcoma of liver

Occupational exposure, it's used to make PVC pipes
What occupational chemicals are a/w lung carcinoma?
Nickel, chromium, beryllium, or silica
What cancers are a/w EBV?
Nasopharyngeal carcinoma (classically a Chinese male or African person), Burkitt lymphoma, CNS lymphoma in AIDS
What cancer is a/w HHV-8?

What 3 examples of people is this classically seen in?
Kaposi Sarcoma

endothelial; purple, raised lesions
classically seen in:
1. Older, E. Euro men -> tx: excision
2. AIDS -> tx: treat virus to boost immune system?
3. Transplant pt -> tx: reduce the immunosuppressive drugs
What cancer is a/w HBV (DNA virus) and HCV (RNA virus)?
Hepatocellular Carcinoma
What 4 carcinogens are a/w hepatocellular carcinoma?
Aflatoxins, alcohol, HBV, and HCV
What cancers are a/w high-risk HPV?

What subtypes of HPV?
Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix

subtypes 16, 18, 31, 33
What cancers are a/w ionizing radiation (ex: nuclear reactor accidents and radiotherapy)?
AML, CML, papillary carcinoma of thyroid

It generates hydroxyl free radicals when it hits water in the tissues
What cancers are a/w nonionizing radiation (ex: UVB sunlight most common source)?
Basal cell carcinoma, squamous cell carcinoma, melanoma of skin

formation of pyrimidine dimers, normally excised by restriction endonuclease, but excessive overexposure can override this defense (defective in xeroderma pigmentosum)
a) Overexpression (in an autocrine loop) of what ocogene is a/w astrocytoma?

b) What is it's function?
a) PDGFB

b) Platelet-derived growth factor

c) Growth factor
a) Amplification of what oncogene is a/w a subset of breast carcinomas?

b) What is it's function?
a) HER2/neu or ERBB2

b) Epidermal growth factor receptor

This mutation can be treated!
a) Point mutation of what oncogene is a/w MEN2A, MEN2B and sporadic medullary carcinoma of the thyroid?

b) What is it's function?
a) RET

b) Neural growth factor receptor

MEN = multiple endocrine neoplasia. if you suspect someone has this, you can test for RET, and if RET is mutated, you can prophylactically remove the thyroid
a) Point mutation of what oncogene is a/w GI stromal tumor?

b) What is it's function?
a) KIT

b) Stem cell growth factor receptor
a) Point mutation of what oncogene is a/w many types of cancers, such as carcinomas, melanoma and lymphoma?

b) What is it's function?
a) RAS gene family

b) GTP-binding protein (a signal transducer)

RAS is a/w a growth factor receptor and attached to GDP, activation leads to phosphorylation to GTP and signals sent to nucleus. GAP cleaves the phosphate and ends the signal. If defective, RAS will send way too much signal to the nucleus!
a) Translocation of what oncogene is a/w CML and some types of ALL (specificially adults)?

b) What is the translocation?

c) What is it's function?
a) ABL

b) t(9;22) with BCR - Philadelphia chromosome (ALL Ph+)

c) Tyrosine kinase (a signal transducer)

The t(9;22) defines CML!
a) Translocation of what oncogene is a/w Burkitt lymphoma?

b) What is the translocation?

c) What is it's function?
a) c-MYC

b) t(8;14) involving IgH

c) Transcription factor (nuclear regulator)

If you have the c-MYC mutation, you WILL get Burkitt. "Starry Sky" appearance. MYC translocates to IgH chromosome, making it on all the time, causing massive overgrowth.
What chromosome is MYC on?
8
What chromosome is IgH on?
14
a) Amplification of what oncogene is a/w Neuroblastoma?

b) What is it's function?
a) N-MYC (n for neuro)

b) Transcription factor (nuclear regulator)
b) Amplification of what oncogene is a/w Lung carcinoma (small cell)?

b) What is it's function?
a) L-MYC (l for lung)

b) Transcription factor (nuclear regulator)
a) Translocation of what oncogene is a/w Mantle cell lymphoma?

b) What is the translocation?

c) What is it's function?
a) CCND1 (cyclin D1)

b) t(11;14) involving IgH

c) Cyclin (cell cycle regulator)

Mantle is next to the follicle in the lymph node
What chromosome is cyclin D1 on?
11
a) Amplification of what oncogene is a/w melanoma?

b) What is it's function?
a) CDK4

b) Cyclin-dependent kinase (cell cycle regulation)
What 2 important tumor suppressor genes regulate the progression from G1 -> S phase.
p53 "traffic cop" and Rb
If DNA repair isn't possible, what is upregulated by p53?
BAX, which disrupts Bcl2 -> cyt c leaks from mito
Li-Fraumeni syndrome is a germline mutation in what?
p53!
Rb "holds" what transcriptioin factor? How does the transcription factor become free to allow transition from G1 to S?
E2F; released when Rb is phosphorylated by cyclinD/CDK4 complex
Germline mutation in Rb obviously is a/w bilateral retinoblastoma, but what else?
osteosarcoma
What normally stabilizes the mito membrane, preventing release of cytochrome C?
Bcl2
What is overexpressed in follicular lymphoma? What is the translocation?
Bcl2, t(14;18)

Normally not a problem in most tissues, but in the lymph node, we want the failed B cells to die!
What chromosome is Bcl2 on?
18
Tumor cells can separate/dissociate from each other by downregulating what?
E-cadherin (and other cell adhesion molecules)
How do tumor cells get through the basement membrane?
Attach to laminin and destroy BM (collagen type IV) via collagenase
What do tumor cells attach to in the extracellular matrix before entering vascular or lymphatic spaces?
Fibronectin
Hematogenous spread is characteristic of sarcomas and what carcinomas (carcinomas usually spread to regional lymph)?
Renal cell carcinoma (via renal vein)
Hepatocellular carcinoma (via hepatic vein)
Follicular carcinoma of thyroid
Choriocarcinoma (makes sense because this is a tumor of placental tissue, specifically trophoblasts, whose job is to find blood vessels)
"Omental caking"
example of seeding of body cavities (peritoneum), characteristic of ovarian carcinoma
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Keratin positive. What category of cancer is this?
Carcinoma (epithelium)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Vimentin positive. What category of cancer is this?
Sarcoma (mesenchyme)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Desmin positive. What category of cancer is this?
Myosarcoma (muscle)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is GFAP positive. What category of cancer is this?
Neuroglia
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Neurofilament positive. What category of cancer is this?
Neurons
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is PSA positive. What category of cancer is this?
Prostatic carcinoma (epithelium)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is ER positive. What category of cancer is this?
Breast carcinoma (epithelium)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Thyroglobulin positive. What category of cancer is this?
Thyroid follicular cells
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is Chromogranin positive. What category of cancer is this?
Small cell carcinoma of lung and carcinoid tumors (both from neuroendocrine cells)
You see a tumor that is poorly differentiated and you aren't sure what it is. Immunohistochemical staining of the tumor shows that it is S-100 positive. What category of cancer is this?
Melanoma
Intermediate filaments that can be tested in immunohistochemical stains are?
Keratin, vimentin, desmin, GFAP, and neurofilament
An example of a serum tumor marker is what?
PSA

can be used for screening, monitoring response to treatment, and monitoring recurrence, but NOT FOR DIAGNOSIS