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USMLE 1 > Pathology- Cellular injury > Flashcards

Pathology- Cellular injury Flashcards

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USMLE® Step 1 flashcards
1
Q

Cellular adaptations

A

Reversible changes that can be physiologic or
pathologic. If stress is excessiveor persistent, adaptations can progress to cell injury.

Hypertrophy, Hyperplasia, Atrophy, Metaplasia, Dysplasia.

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2
Q

Cell injury

  • Reversible
  • Irreversible
A
  • Cellular/ mitochondrial swelling, Membrane blebbing, Nuclear chromatin clumping, Ribosomal/polysomal
    detachment.
  • Rupture of lysosomes and autolysis, Mitochondrial permeability, Plasma membrane damage = leakage of
    cytosolic enzymes into serum, influx of Ca2+ activating
    lysosomal enzymes.
Nucleus:
pyknosis (condensation)
or
karyorrhexis (fragmentation)
or
karyolysis (fading)
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3
Q

Apoptosis

A

Characterized by deeply eosinophilic cytoplasm and basophilic nucleus, pyknosis, and karyorrhexis.

Cell membrane typically remains intact without significant inflammation (unlike necrosis).

DNA laddering (fragments in multiples of 180 bp) is a sensitive indicator of apoptosis.

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4
Q

Apoptosis

Intrinsic (mitochondrial) pathway

A

Involved in tissue remodeling in embryogenesis. Occurs when a regulating factor is withdrawn from a proliferating cell population. Also occurs after exposure to injurious stimuli

Regulated by Bcl-2 family of proteins. BAX and BAK are proapoptotic (activate Cytochrome C), while Bcl-2 and Bcl-xL are antiapoptotic.

*Bcl-2 overexpression (eg, follicular lymphoma t[14;18]), decrease caspase activation, tumorigenesis.

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5
Q

Apoptosis

Extrinsic (death receptor) pathway

A

2 pathways:
ƒ Ligand receptor interactions (FasL binding to Fas [CD95] or TNF-α binding to its receptor).

ƒ Immune cell (cytotoxic T-cell release of perforin and granzyme B)

*Defective Fas-FasL interactions cause autoimmune lymphoproliferative syndrome.

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6
Q

Necrosis and types

A

Enzymatic degradation and protein denaturation of cell due to exogenous injury. Inflammatory process (unlike apoptosis).

Coagulative, Liquefactive, Caseous, Fat, Fibrinoid, Gangrenous.

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7
Q

Coagulative Necrosis

  • Seen in
  • Histology
A

Ischemia/infarcts in most tissues (except brain).

Preserved cellular architecture (cell outlines seen), but nuclei disappear; High cytoplasmic binding of eosin stain (Higher eosinophilia; red/pink color).

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8
Q

Liquefactive Necrosis

  • Seen in
  • Histology
A

Bacterial abscesses, brain infarcts.

Early: cellular debris and macrophages
Late: cystic spaces and cavitation (brain)

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9
Q

Caseous Necrosis

  • Seen in
  • Histology
A

TB, systemic fungi (eg, Histoplasma capsulatum), Nocardia

Fragmented cells and debris surrounded by lymphocytes and macrophages (granuloma).

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10
Q

Fat Necrosis

  • Seen in
  • Histology
A

Enzymatic: acute pancreatitis (saponification of peripancreatic fat).
Nonenzymatic: traumatic (eg, injury to breast tissue)

Outlines of dead fat cells without peripheral nuclei; saponification of fat (combined with Ca2+) appears dark blue on H&E stain.

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11
Q

Fibrinoid Necrosis

  • Seen in
  • Histology
A

Immune reactions in vessels (eg, polyarteritis nodosa), preeclampsia, hypertensive emergency

Vessel walls are thick and pink

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12
Q

Gangrenous Necrosis

  • Seen in
  • Histology
A

Distal extremity and GI tract, after chronic ischemia.

Dry: ischemia. Coagulative
Wet: superinfection. Liquefactive superimposed on coagulative

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13
Q

Regions most vulnerable to hypoxia/ischemia and subsequent infarction:

A

Brain: ACA/MCA/PCA boundary areas

Heart: Subendocardium (LV)

Kidney: Straight segment of proximal tubule (medulla) Thick ascending limb (medulla)

Liver: Area around central vein (zone III)

Colon: Splenic flexure, rectum

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14
Q

Red infarct

A

Red (hemorrhagic) infarcts occur in venous occlusion and tissues with multiple blood supplies, such as liver, lung, intestine, testes; reperfusion (eg, after angioplasty). Reperfusion injury is due to damage by free radicals.

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15
Q

Pale infarct

A

Pale (anemic) infarcts occur in solid organs with a single (end-arterial) blood supply, such as heart, kidney, and spleen.

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16
Q

Inflammation Cardinal signs

A 
Rubor (redness), 
calor (warmth)
Tumor (swelling)
Dolor (pain)
Functio laesa (loss of function)
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17
Q

Inflammation Systemic manifestations (acute-phase reaction)

A

Fever
Leukocytosis
plasma acute-phase proteins

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18
Q

Leukemoid reaction

A

severe elevation in WBC (> 40,000 cells/mm³) caused by some stressors or infections (eg, Clostridium difficile).

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19
Q

Acute phase reactants

  • Positive
  • Negative
A
  • Ferritin, Fibrinogen, Serum amyloid A, Hepcidin, C-reactive protein. “FFiSH in the C (sea)”
  • Albumin, Transferrin
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20
Q

Erythrocyte sedimentation rate (ESR)

A

Products of inflammation (eg, fibrinogen) coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube Higher ESR.

21
Q

diseases with high ESR

A
  • Most anemias
  • Infections
  • Inflammation (eg, giant cell [temporal] arteritis, polymyalgia rheumatica).
  • Cancer (eg, metastases, multiple myeloma)
  • Renal disease (end-stage or nephrotic syndrome)
  • Pregnancy
22
Q

diseases with Low ESR

A
  • Sickle cell anemia (altered shape)
  • Polycythemia (RBCs “dilute” aggregation factors)
  • HF
  • Microcytosis
  • Hypofibrinogenemia
23
Q

Inflammasome

A

Cytoplasmic protein complex that recognizes products of dead cells, microbial products, and crystals (eg, uric acid crystals) activation of IL-1 and inflammatory
response.

24
Q

Leukocyte extravasation has 4 steps:

A

margination and rolling, adhesion, transmigration, and

migration (chemoattraction).

25
Q

Acute inflammation cells

A

Neutrophils

Macrophages predominate in the late stages of acute inflammation (peak 2–3 days after onset.

26
Q

Margination and rolling

  • Vasculature/Stroma
  • Leukocyte
A

E-selectin (upregulated by TNF and IL-1) binds to Sialyl-LewisX

P-selectin (released from Weibel- Palade bodies) binds to Sialyl-LewisX

GlyCAM-1, CD34 binds to L- selectin

*defective in leukocyte adhesion deficiency type 2 (Lower Sialyl- LewisX)

27
Q

Tight binding (adhesion)

  • Vasculature/Stroma
  • Leukocyte
A

ICAM-1 (CD54) binds to CD11/18 integrins (LFA-1, Mac-1)

VCAM-1 (CD106) binds to VLA-4 integrin

*defective in leukocyte adhesion deficiency type 1 (lower CD18 integrin subunit)

28
Q

Diapedesis (transmigration)

  • Vasculature/Stroma
  • Leukocyte
A

PECAM-1 (CD31) binds to PECAM-1 (CD31)

29
Q

Migration

A

Chemotactic products released in response to bacteria: C5a, IL‑8, LTB4, kallikrein, platelet-activating factor

30
Q

Chronic inflammation

  • Stimuli
  • Outcomes
A

Persistent infections (eg, TB, T pallidum, certain fungi and viruses) = type IV hypersensitivity, autoimmune diseases, prolonged exposure to toxic agents (eg, silica) and foreign material.

Scarring, amyloidosis and neoplastic transformation

31
Q

Chronic inflammation

- Mediators

A

ƒ Th1 cells secrete INF-γ, macrophage classical activation (proinflammatory)

ƒ Th2 cells secrete IL-4 and IL-13 Ž macrophage alternative activation (repair and antiinflammatory)

32
Q

Granulomatous diseases

  • Bacterial
  • Fungal
  • Parasitic
  • Chronic granulomatous disease
A

ƒƒMycobacteria (tuberculosis, leprosy)
ƒƒ Bartonella henselae (cat scratch disease)
ƒƒ Listeria monocytogenes (granulomatosis infantiseptica)
ƒƒ Treponema pallidum (3° syphilis)

  • Endemic mycoses (eg, histoplasmosis)
  • schistosomiasis
33
Q

Granulomatous diseases

  • Autoinflammatory
  • Foreign material
A 
ƒƒ Sarcoidosis
ƒƒ Crohn disease
ƒƒ Primary biliary cholangitis
ƒƒ Subacute (de Quervain/granulomatous)
thyroiditis
ƒƒGranulomatosis with polyangiitis (Wegener)
ƒƒ Eosinophilic granulomatosis with
polyangiitis (Churg-Strauss)
ƒƒGiant cell (temporal) arteritis
ƒƒ Takayasu arteritis
  • Berylliosis, talcosis, hypersensitivity pneumonitis
34
Q

Granulomatous diseases

A

Anti-TNF drugs can cause sequestering granulomas to break down and disseminated disease. Always test for latent TB before starting anti-TNF therapy.

Associated with hypercalcemia due to calcitriol (1,25-[OH]2 vitamin D3) production

35
Q

Types of calcification: Dystrophic calcification

  • Ca+2 deposition
  • Extent
  • Etiology
  • Associated conditions
A

In abnormal tissues

Tends to be localized

2° to injury or necrosis

TB (lung and pericardium) and other granulomatous infections, liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, congenital CMV, toxoplasmosis, rubella, psammoma bodies, CREST syndrome, atherosclerotic plaques can
become calcified.

36
Q

Types of calcification: Metastatic calcification

  • Ca+2 deposition
  • Extent
  • Etiology
  • Associated conditions
A

In normal tissues

Widespread

2° to hypercalcemia or high calcium-phosphate product levels

Predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly;  pH favors Ca2+ deposition).

37
Q

Lipofuscin

A

A yellow-brown “wear and tear” pigment associated with normal aging.

Formed by oxidation and polymerization of autophagocytosed organellar membranes.

38
Q

Scar formation

A

Occurs when repair cannot be accomplished by cell regeneration alone. Nonregenerated cells (2° to severe acute or chronic injury) are replaced by connective tissue. 70–80% of tensile strength regained at 3 months; little tensile strength regained thereafter.

39
Q

SCAR TYPE: Hypertrophic

  • Collagen synthesis
  • Organization
  • Extent
  • Recurrence
  • Predisposition
A

type III collagen

Parallel

Confined to borders of original wound

Infrequent

none

40
Q

SCAR TYPE: Keloid

  • Collagen synthesis
  • Organization
  • Extent
  • Recurrence
  • Predisposition
A

Type I and III collagen

Desorganized

Extends beyond borders of original wound with “claw-like” projections typically on earlobes, face, upper extremities

Frequent

Darker skin

41
Q

Wound healing

- Tissue mediators

A 
FGF
VEGF
TGF-B
PDGF
Metalloproteinases
EGF
42
Q

PHASE OF WOUND HEALING
1. Inflammatory (up to 3 days after wound)

  1. Proliferative (day 3–weeks after wound)
  2. Remodeling (1 week–6+ months after wound)
A

Clot formation, vessel permeability and neutrophil migration into tissue; macrophages clear debris 2 days later.

Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound contraction (mediated by myofibroblasts).

Type III collagen replaced by type I collagen. Collagenases (require zinc to function) break down type III collagen.

*Delayed wound healing in vitamin C deficiency, copper
and zinc deficiency.

43
Q

Light criteria

A

Fluid is exudative if ≥ 1 of the following criteria is met:
ƒƒ Pleural effusion protein/serum protein ratio > 0.5
ƒƒ Pleural effusion LDH/serum LDH ratio > 0.6
ƒƒ Pleural effusion LDH > 2⁄3 of the upper limit of normal for serum LDH

44
Q

Amyloidosis

A

Abnormal aggregation of proteins (or their fragments) into β-pleated linear sheets, insoluble fibrils, cellular damage and apoptosis.

Amyloid deposits visualized by Congo red stain, polarized light (apple green birefringence), and H&E stain

45
Q

Systemic amyloidosis

  • Primary amyloidosis
  • Secondary amyloidosis
  • Dialysis-related amyloidosis
A

AL (from Ig Light chains). Seen in plasma cell disorders
and multiple myeloma.

Serum Amyloid A (AA). Seen in chronic inflammatory
conditions, eg, rheumatoid arthritis, IBD, familial
Mediterranean fever, protracted infection.

β2-microglobulin Seen in patients with ESRD and/or on long-term dialysis.

46
Q

Systemic Amyloidosis Manifestations

A

ƒƒ Cardiac (eg, restrictive cardiomyopathy, arrhythmia)
ƒƒGI (eg, macroglossia, hepatomegaly)
ƒƒ Renal (eg, nephrotic syndrome)
ƒƒHematologic (eg, easy bruising, splenomegaly)
ƒƒNeurologic (neuropathy)
ƒƒMusculoskeletal (carpal tunnel syndrome)

47
Q

Localized amyloidosis

  • Alzheimer disease
  • Type 2 diabetes mellitus
  • Medullary thyroid cancer
  • Isolated atrial amyloidosis
  • Systemic senile (agerelated) amyloidosis
A

β-amyloid protein. Cleaved from amyloid precursor
protein (APP).

Islet amyloid polypeptide (IAPP). Caused by deposition of amylin in pancreatic islets.

Calcitonin (A Cal)

ANP. Common in normal aging, risk of atrial fibrillation.

Normal (wild-type) transthyretin (TTR). Seen predominantly in cardiac ventricles

48
Q

Hereditary amyloidosis

  • Familial amyloid cardiomyopathy
  • Familial amyloid polyneuropathies
A

Mutated transthyretin (ATTR). Ventricular endomyocardium deposition, restrictive cardiomyopathy, arrhythmias 5% of African Americans are carriers of mutant allele.

Mutated transthyretin (ATTR). Due to transthyretin gene
mutation.

USMLE 1 (73 decks)

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