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USMLE > Generalized Pathology > Flashcards

Generalized Pathology Flashcards

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USMLE® Step 1 flashcards
1
Q

Intrinsic Mitochondrial Apoptosis Pathway

A
  • occurs after a regulating factor is withdrawn from cell population, exposure to injurious stimuli (DNA damage = radiation, toxins, free radicals, hypoxia), protein misfolding (ER stress)
  • BCL2 = antiapoptotic, BAX & BAK = pro apoptotic
  • BCL2 sits on mitochondrial membrane and binds to APAF1 to inhibit release of cytochrome C
  • when cell injury occurs BAX and BAK dislodge BCL2 and form a pore that allows release of Cytochrome C which activates initiator caspases then executationer caspases causing cell break down
  • Caspases 9 and Cytochrome C specific
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2
Q

Extrinsic Death Receptor Apoptotic Pathway

A
  • there are 2 pathways which are FasLigand binding or immune cell (CD8 release of perforin and granzymes)
  • these activate FADD and adaptor proteins that activate inactive caspases and then executioner caspases to allow for apoptosis
  • Caspases 8 specific

Ex: Negative T-cell Selection in thymus

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3
Q

Characteristics of Apoptosis

A
  • deeply eosinophilic cytoplasm = pink cytoplasm
  • cell shrinkage
  • nuclear shrinkage (pyknosis)
  • basophilia
  • membrane blebbing
  • nuclear fragmentation (karyorrhexis)
  • Formation of apoptotic body that is phagocytosis
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4
Q

Necrosis

A
  • doesn’t make decision for cell death = passive response to injury and no energy required
  • always pathological
  • occurs sporadically
  • enzymatic degradation and protein desaturation of cell due to exogenous injury
  • there is a leak of cell contents through damaged plasma membrane in to extra cellular space ==> inflammation
  • overall unlregulated cell death from = damage to cell membranes, loss of ion homeostasis, desaturation of cellular proteins
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5
Q

Coagulative Necrosis

A
  • Ischemia/infarcts in most tissues except brain
  • due to denatured proteins and then enzymatic degradation
  • cell outline is preserved and there is increased cytoplasmic binding of acidophillic dyes = no nucleus found
  • area of infarct is often wedge shaped
  • red infarction = blood re-enters loosely organized tissue = testicle and lungs
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6
Q

Liquefactive Necrosis

A
  • Bacterial abscesses, pancreatitis, and Brain infarcts (micro glial cells digest infarcted brain tissue)
  • due to neutrophils that release lysosomal enzymes that digest the tissue, enzymatic degradation first, and then proteins denature
  • Histo: Early –> cellular debris and macrophages. Late –> cystic spaces and cavitation
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7
Q

Caseous Necrosis

A
  • from TB or Systemic fungi (histoplasmosis), Nocardia
  • due to macrophages that wall off the infecting microorganism –> granular debris
  • fragmented cells and debris surrounded by lymphocytes and macrophages
  • soft and friable necrotic tissue with cottage cheese like appearance
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8
Q

Fat Necrosis

A
  • Enzymatic = acute pancreatitis or Nonenzymatic = breast trauma
  • in breast fat necrosis can present as a mass
  • damaged fat releases lipase so which breaks down fatty acids in cell membranes. Fatty acids attract calcium
  • Histo: outline of dead fat cells without peripheral nuclei; saponification of fat with calcium
  • appears dark blue on H&E
  • necrotic adipose tissue attract calcium = fat sapinofication
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9
Q

Fibrinoid Necrosis

A

Necrotic damage to blood vessel wall

  • immune reactions in vessels (inflammatory process involving arteries) or malignant hypertension
  • immune complexes combine with fibrin –> vessel wall damage
  • Histo: vessel walls are thick and pink
  • can also be seen in young women that have pre-eclampsia = fibrinoid necrosis of the placental blood vessels
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10
Q

Gangrenous Necrosis

A
  • distal extremity after chronic ischemia
  • Dry = ischemia ==> coagulative
  • Wet = superinfection of dead ischemic tissue ==> liquefactive
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11
Q

Apoptosis vs. Necrosis

A

Apoptosis: regulated, usually physiologic, plasma membrane remains intact, no leakage, and no inflmmatory reaction, uses energy

Necrosis = passive response to injury, always pathological, disruption of plasma membrane, cell swelling, no phagocytosis, leakage of contents, inflammatory response

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12
Q

Chromatolysis

A
  • involves neuronal cell body following axon injury
  • changes reflect an increase in protein synthesis in effort to repair the damaged axon
  • Characterized by: round cellular swelling displacement of the nucleus to the periphery, dispersion of Nissl substance throughout cytoplasm
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13
Q

Pathological Calcifications

A

Dystrophic = calcium deposition in abnormal tissues after injury or necrosis, tends to be localized, patient is normally normocalcemic

Metastatic = widespread calcium deposition in normal tissues, secondary to hypercalcemia or high calcium phosphate production levels
- affects tissues that lose acid quickly and are alkaline ==> kidney , lung, and gastric mucosa

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14
Q

Leukocyte Extravasation

A
  • occurs at post capillary venues

- margination and rolling, tight binding, diapedesis, and migration

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15
Q

Scar Formation

A
  • 70-80% of tensile strength regained at 3 months, little will be regained after
    Two types of Scars
  • hypertrophic scars = slight increase in collagen synthesis, parallel collagen arrangement, confined to borders of original wound, infrequently recur after resection
  • Keloid scars = very increased collagen synthesis, disorganized collagen arrangement, extends beyond borders of original wound, frequently recur after resection, and higher incident in AA.
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16
Q

Exudate vs. Transudate

A

Exudate = due to lymphatic obstruction, inflammation/infection, malignancy

  • protein rich, cellular
  • high specific gravity

Transudate = thin, due to increased hydrostatic pressure or decreased oncotic pressure, sodium retention

  • hypo cellular
  • protein poor
  • decreased specific gravity
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17
Q

Amyloidosis

A
  • abnormal aggregation of proteins into beta pleated sheaths–> damage and apoptosis
  • AL (primary) = due to deposition of proteins from Ig Light chains
  • AA (secondary) = due to chronic inflammatory conditions. Composed of serum amyloid A
  • Dialysis related = fibrils composed of B2-micro globulin in ESRD patients. Deposits in joints. Can cause carpal tunnel
  • Heritable = due to transthyretin gene mutation
  • Age-related (senile) systemic = due to deposition of normal wild type transthyretin in myocardium and other sites. Slower progression of cardiac dysfunction relative to AL amyloidsis
  • Familial amyloid cardiomyopathy = mutated serum transthyretrin deposits in the heart leading to restrictive cardiomyopathy
  • Organ specific = amyloid deposition in a single organ. (Beta amyloid protein clever from Amyloid precursor protein APP = Alzheimer’s disease) or (Islet amyloid polypeptide from insulin = Diabetes type 2 caused by deposition of amyloid in pancreatic islets)
  • medullary carcinoma of the thyroid = calcitonin produced by tumor cells deposits within the tumor (tumor cells in an amyloid background)
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18
Q

Lipofuscin

A
  • yellow brown wear and tear pigment seen in normal aging
  • formed by oxidation and polymerization of auto phagocytosis organelles membranes
  • will see deposits in biopsy of autopsy in an elder person
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19
Q

P-glycoprotein

A
  • also known as multi drug resistance protein 1 (MDR1)
  • classically seen in adrenal cell carcinoma but also expressed by other cells
  • used to pump out toxins including chemo drugs
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20
Q

Plasia’s

A
  • dysplasia, hyperplasia, and meta plasia = reversible
  • anaplasia, neoplasia, and desmoplasia = irreversible
  • desmoplasia = fibrous tissue formation in response to neoplasm
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21
Q

Tumor Nomenclature

A

Carcinoma

  • from epithelial origin
  • spreads via lymphatics

Sarcoma

  • spread hematogenously
  • mesenchymal origin

Hamartoma = disorganized overgrowth of tissues in their native location

Choristoma = normal tissue in a foreign location

22
Q

Common metastases

A

Lung> Breast> Prostate> Melanoma > GI ===> metastasize to the Brain

Colon» stomach> pancreas ===> Liver

Prostate, breast> lung, thyroid, kidney ==> Bone (predilection for axial skeleton) = usually osteolytic except prostate

23
Q

Meta plasia

A
  • apocrine metaplasia of breast due to fibrocystic changes = no increased rink of cancer
  • Vitamin A deficiency can result in metaplasia = results in metaplasia of conjunctiva which causes a thickening and change from goblet/cell columnar epithelium of conjunctiva to the keratinizing squamous epithelium ==> keratomalacia

Keratomalacia = dry eyes that can lead to destruction of cornea and blindness

Mesenchymal tissues can also undergo metaplasia
- myositis ossificans = inflammation of skeletal muscle results in meta plastic production of bone in skeletal muscle

24
Q

Carbon Monoxide Poisoning

A

CO binds hemoglobin binds more avidly than oxygen
PaO2 normal but SaO2
- exposures include smoke from fires and exhaust from cars or gas heaters
- Classic finding = cherry red appearance of skin
- Early sign of exposure = headache
- significant exposure = leads to coma and death

25
Q

Reversible Injury

A
  • cellular swelling = leads to loss of micro villi and membrane blebbing
  • swelling of RER results in dissociation of ribosomes and decreased protein synthesis
26
Q

Irreversible Injury

A
  • Hallmark = membrane damage
  • plasma membrane damage = cytosolic enzymes leak into serum and additional calcium entering cell
  • mitochondrial membrane damage = loss of ETC chain (inner mitochondrial membrane) and cytochrome c leaking into cytosol (activates apoptosis)
  • lysosomal membrane damage = hydrologic enzymes leaking into cytosol which is activated by high intra cellular calcium
27
Q

Cell death

A

Hallmark = loss of the nucleus

  • nuclear condensation (pyknosis)
  • fragmentation (karyorrhexis)
  • dissolution (karyolysis)
28
Q

CCl4 Free Radical injury

A
  • converted to CCl3 by CYP450 hepatocytes
  • results in cell injury with swelling of RER, causing ribosomal detachment, and impaired protein synthesis
  • decreased apolipoproteins lead to fatty changes in the liver
29
Q

Familial Mediterranean Fever

A
  • autosomal recessive
  • dysfunction of neutrophils
  • occurs in person’s of Mediterranean origin
  • presents with episodes of fever and acute serosa leukemia inflammation
  • High SAA during attacks deposits as AA amyloid
30
Q

Alfatoxin

A
  • from aspergillus that can contaminate stored rice and grains
  • causes Hepatocellular carcinoma
31
Q

Arsenic

A
  • from cigarette smoke

- causes squamous cell cancer of skin, lung, cancer, and angiosarcoma of liver

32
Q

Nitrosamines

A
  • found in smoked foods and is responsible for high rates of stomach cancer in Japan
  • associated with intestinal type of stomach cancer
33
Q

Napthylamine

A
  • from cigarrette smoke

- urothelial carcinoma of bladder

34
Q

Vinyl Chloride

A
  • occupational exposure used to make polyvinyl chloride for use in pipes
  • causes angiosarcoma of liver
35
Q

Oncogenic Viruses

A

EBV = nasopharyngeal carcinoma, Burkett lymphoma, and CNS lymphoma in AIDS

HHV-8 = kaposi sarcoma

HBV and HCV = hepatocellular carcinoma

HTLV1- Adult T-cell leukemia/lymphoma

High Risk HPV = squamous cell carcinoma of Vulva, vagina, anus, and cervix

36
Q

Radiation

A

Ionizing = nuclear accidents and radiotherapy

  • generates hydroxyl free radicals
  • AML, CML, and papillary carcinoma of thyroid
  • activates the G2/M checkpoint resulting in chromosomal abnormalities in mitosis

Nonionizing (UVB sunlight)

  • results in formation of pyrmidine diners which are normally excised by restriction endonucelases = Xeroderma Pigmenetosum
  • Basal cell carcinoma, Squamous cell carcinoma, melanoma of skin
37
Q

Categories of OncogenEs

A
  • Growth Factor
  • Growth Factor receptors
  • Signal Transducers
  • Nuclear regulators
  • Cell cycle regulators

READ PAGE 26 on PATHOMA

38
Q

Retinoblastoma

A
  • holds the E2F transcription factor that is necessary for transition from G to S phase
  • E2F is released when RB is phosphorylates by Cyclin D or CDK complex
  • Both copies of RB gene must be knocked out for tumor formation
  • Sporadic mutation (both hits are somatic) = unilateral retinoblastoma
  • Germline mutation (2nd hit is somatic) = familial retinoblastoma ==> bilateral retinoblastoma and osteosarcoma
39
Q

Follicular Lymphoma

A
  • t(14,18)
  • over expression of BCL2 (on 18)
  • prohibition of apoptosis
  • B cells that normally undergo apoptosis during somatic hyper mutation in the lymph node germinal center accumulate leading to lymphoma
40
Q

Tumor Invasion and Spread

A
  1. Tumor cell down regulates E-Catherine
  2. The tumor cell attaches to laminitis and destroys basement membrane type 4 collagen via collagense
  3. Tumor cell attaches to fibronectin in the ECM and spread locally
  4. Entrance into vascular or lymphatic spaces allows for metastasis (distant spread)
41
Q

Routes of Metastasis

A 
Carcinoma = spreads through lymphatics
Sarcomas = spreads through blood

Exceptions of carcinoma that spread through blood

  • Renal cell carcinoma = spread through renal vein
  • Hepatocellular carcinoma = invades hepatic vein
  • Follicular carcinoma of thyroid
  • Choriocarcinoma
42
Q

What is the only way to make a diagnosis of cancer?

A

Biopsy or excision is required before a tumor can be classified as benign or malignant with certainty

43
Q

Intermediate filaments

A

Differ based on cells
- used for immunohistochemistry to identify a tumor

Keratin = Epithelium ==> carcinoma
Vimentin = Mesenchyme ==> sarcoma
Desmin = Muscle
GFAP = neuroglia 
Neurofilament = neurons
44
Q

Chromogranin

A

Used to find small cell carcinoma or carcinoid tumors

  • both derived from Neuroendocrine cells
  • use with immunohistochemistry
45
Q

S-100

A

Tumor marker for melanoma, schwannoma, and langerhans cell histiocytosis

46
Q

Grading vs. Staging of Cancer

A

Grading = differentiation
- well differentiation cancers have better prognosis than poor
- determines prognosis
Staging = TMN = size or depth = T, metastasis, and nodal involvement
- KEY Prognostic factor; more important than grade
- metastasis is the single most important prognostic factor

47
Q

Gastric Cancer

A
  • more prevalent in JApan
48
Q

Hemangioma, teratomas, fibromatoses

A
  • common pediatric neoplasms that are benign
  • Grow slowly and remain localized
  • do not invade or metastasize
49
Q

Radon Gas

A
  • second most common cause for lung cancer that is squamous cell after smoking
  • radon seeps from soil and may collect in houses
50
Q

Flow cytometry

A
  • detects the degree of aneuploidy from the DNA content

- if neoplasm is aneuploidy it is more aggressive

51
Q

Carcinoma vs. Sarcoma

A

Carcinoma = derived from epithelium and contain cytokeratins

Sarcoma = derived from mesenchymal cells and contain vimentin

USMLE (14 decks)

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