Pathology week 1 Flashcards

1
Q

Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: hypertrophy

A

Hypertrophy: increase stress leads to an increase in size of cells results in increase of organ. Trying to work capability. May occur with hyperplasia = hypertropic organ. Can result in cellular injury if stress is not relieved.
Examples: pathologic: heart or physiologic (uterus)
Cell needs to get larger = cytoskeleton needs to grow = gene activation and protein synthesis; for a larger cell more organelles will need to be produced

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2
Q

Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: hyperplasia

Uncontrolled hyperplasia can lead to what?

A

Hyperplasia: increase in cell number in response to stress. Important for wound healing - a balanced and controlled event. Uncontrolled can lead to neoplasia/cancer
Physio: hormonal, compensatory (pregnancy)
Patho: (eg endometrial hyperplasia) excess of hormones or growth factor can progress to dysplasia and eventually to cancer; another example prostatic hyperplasia (prostate)
Produced from stem cells
Exception: Benign prostatic hyperplasia (BPH) no increased risk of cancer

Example: uterus during pregnancy hyperplasia and hypertrophy occur together

    • Exception: permanent cells undergo hypertrophy only (lack stem cells)
  • permanent cells: cardiac myocytes, skeletal, nerve **
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3
Q

Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: Atrophy

A

Atrophy: decrease in stress leads to decrease in cell size and/or number, decrease in function (cells survive). Mech: decrease workload, innervation, blood supply, endocrine, stimulation, nutrition, pressure
Mech: decreased protein synth, increased degradation in cells, autophagy “self eating” (vacuoles fuse with lysosomes
* Decrease in number of cells occurs via apoptosis
*Decrease in size: ( 1) ubiquitin-proteosome degradation of the cytoskeleton (intermediate filaments get tagged and then destroyed by the ubiquitin proteosome; ( 2) autophagy of cellular components fuse with lysosomes and get consumed

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4
Q

Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: metaplasia

A

Metaplasia: reversible change from one cell type to another, protective to the stress.
Mechanism:Genetic reprogramming of stem cells, not transdifferentiation of mature cells. If it persists, may predispose to neoplastic transformation (sq-lung)
- most commonly involves surface of epithelium
example: Barrett esophagus: esophagus lined by squamous epithelium vs stomach lined by columar epithelium (better at handling acid) = esophagus will change cell type in acid reflux (GERD); secondary example is with smoking in the lungs
can progress to cancer
** EXCEPTION: apocrine metaplasia does not increase risk for cancer (fibrocystic change in the breast) **
Example: Vitamin A deficiency (risk for night blindness) also necessary for proper maturation of the immune system and epithelium
conjutiva of the eye
(promytocytic leukemia)
Mesencymal (connective) tissue can undergo metaplasia:
- Example: myositis ossificans: trauma of the skeletal muscle

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5
Q

Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: dysplasia, aplasia, hypoplasia

A

Dysplasia: disordered cellular growth, refers to proliferation of precancerous cells (eg. CIN). Arises from longstanding pathologic hyperplasia or metaplasia
** DYSPLASIA IS REVERSIBLE, once the stress is removed **

Aplasia: failure of growth during embryogenesis (unilateral renal agenesis = 1 kidney)

Hypoplasia: decrease in cell production during embryogenesis, results in relatively small organ (example: streak ovary in Turner Syndrome)

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6
Q

Describe the hypoxia cell injury process

A

Hypoxia: (oxygen deprivation) final electron acceptor in the electron transport chain, so lack oxygen = low ATP = cellular injury [most common type of injury]
Ischmia: decreased blood flow through an organ can occur through decrease in artery perfusion (example atherosclerosis) and vein drainage (** bud chiari syndrome - thrombosis of the hepatic vein infarction in the liver, most commonly caused polycythemia vera, other cause lupus anticoagulants **) or even systemic (shock)

Hypoxemia: low partial pressure of O2 in blood PaO2 < 60mm, SaO2 <), diffusion defect, V/Q mismatch (blood bypasses oxygenated lung)
Decreased O2 carrying capacity arises with hemoglobin (Hb) loss or dysfunction
Anemia (decrease in RBC mass); PaO2 normal, SaO2 normal
**Carbon monoxide poisoning (CO binds hemoglobin more avidly (100x more) than O2, SaO2 decreased, PaO2 normal), common exposure from smoke fires, exhaust from cars or gas heaters; classic finding skin is cherry red and early sign is a headache it can lead to coma and death **
**Methemoglobinemia: Iron in heme is oxidized to Fe3+ which cannot bind O2 (Fe2+ binds O2) seen with oxidant stressors (sulfa and nitrate drugs) or in new borns
Classic finding: cyanosis with chocolate-colored blood
Treatment: IV methylene blue **

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7
Q

Why does Low ATP disrupt key cellular functions?

A

Na - K pump (requires ATP): if not function Na is retained and cell will swell as water is pulled into the cell
Ca pump: is kept low in the cystol, and if low ATP it will build and it will activate enzymes that shouldn’t
Aerobic glycolysis: low ATP would lead to increase in lactic acid via anaerobic glycosis and decrease the pH would cause precipitation of DNA and enzymes

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8
Q

Initial phase of injury / signs to a cell:

A

reversible = cellular swelling (hallmark sign) and leads to loss of microvilli; membrane blebbing, and swelling of RER (ribosomes pop off with decrease of protein synth)

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9
Q

Irreversible damage of a cell:

A

Irreversible: membrane damage (hallmark sign):

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10
Q

Discuss membrane damage to the plasma membrane, inner mitochondrial membrane, and lysome membrane

A

Plasma membrane: enzymes leak out into the blood stream ie cardiac infarction, blood draw can be tested for cardiac enzymes showing irreversible damage; calcium can rush once membrane is damaged

Inner mitochonral membrane: location of electron transport chain, once damaged is irreversible; cytochrome C is in the inner mitochondria and if it leaks out it will activate apoptosis

Lysome membrane: if damaged hydrolytic enzymes leak into cytosol

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11
Q

Describe cell death signs:

A

Cell death = loss of nucleus (morphologic hallmark)
pyknosis (nucleus shrinks down), karyorrhexis (nucleus breaks up into big pieces), karyolysis (broken into basic components)

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12
Q

Describe necrosis:

A

Necrosis: is always pathologic (murder!)

  • death of a large group of cells followed by acute inflammation
  • hallmark: eosinophilia - increased “pink” on H&E, myelin figures, calcification of fatty acids, breaking apart of the nucleus karyolysis = pyknosis = karyorrhexis
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13
Q

What is cogaulative necrosis?

A

Coagulative necrosis: tissue remains firm and shape and organ are preserved by coagulation of cellular proteins, nucleus disappears, SEEN WITH ISCHEMIA of any organ EXCEPT the brain

  • area of infarcted tissues is often wedge shaped (wedge points to the point of occlusion) and pale

Red infarction: arises if blood re-enters and tissue is loosely reorganized (testicular - vein gets blocked, but blood still flows in through the artery and pulmonary)

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14
Q

What is liquefactive necrosis?

A

Liquefactive necrosis: necrotic tissue that becomes liquefied (enzymatic lysis of cells and protein results in liquification)

- brain infarction: proteolytic enzymes from microglial cells liquify brain)
- abcess: proteolytic enzymes from neutrophils
- pancreatitis: proteolytic enzymes from pancreas liquify the parenchyma
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15
Q

What is gangrenous necrosis:

A

Gangrenous necrosis: coagulative necrosis that resemble mummified tissue (multiple layers) (dry gangrene)

  • characteristic of ischemia of lower limb and GI tract
  • if superimposed infection of dead tissues occurs then liquefactive necrosis ensues (wet gangrene)
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16
Q

What is caseous necrosis:

A

Caseous necrosis: soft friable necrotic tissue with “cottage cheese like” appearance, combination of coagulative and liquefactive necrosis
- characteristic of granulomatous inflammation due to TB or fungal infection

17
Q

What is fat necrosis:

A

Fat necrosis: necrotic adipose tissue with chalky-white appearance due to deposition of calcium // very purple on H&E stain
- characteristic of fat trauma (breast) and pancreatitis-mediated damage of peripancreatic fat (can present as a mass)
** saponification: fatty acids released by trauma or lipase join with calcium - example of dystrophic calcification, normal serum calcium and phospate **
metastatic calcification occurs with high serum calcium or phosphate levels lead to calcium deposition in normal tissues (hyperparathydroidism leading to nephrocalcinosis)

18
Q

Fibrinoid Necrosis:

A

necrotic damage to blood vessel wall, leaking of protein (including fibrin) into the wall (bright pink staining)

  • characteristic of malignant hypertension (medical emergency - very high blood pressure) and vasculitis
  • *30 y/o women with fibroid necrosis? pregnant with pre-eclampsia of the placenta
19
Q

Describe apoptosis

A

Apoptosis: can be a normal function or pathologic (cellular suicide!)
- energy dependent genetically programmed cell death (single or small groups of cells)
example: endometrial shedding during menstrual cycle, removal of cells during embryogensis (formation of individual toes and fingers), CD8+ T cell-mediated killing of virally infected cells
Morphology: apoptosis means falling of leaves: cell shrinks (becomes eosinophilic, nucleus condenses and fragments, apoptoic bodies fall from cell and are removed by macrophages (not followed by inflammation)

20
Q

provide examples of physio and patho causes of apoptosis

A

Physiologic
• Embryogenesis
• Hormone-dependant tissues, eg endometrium
• Cell loss in proliferating tissues (thymus, bone marrow)
• Eliminate self reactive lymphocytes
• Programmed death: neutrophils- served purpose

Pathologic (genetically altered)
• DNA damage: radiation, cytotoxic drugs, hypoxia, temperature extremes
• Accumulation of misfolded proteins
• Cell injury from infections (viral)
• Organ atrophy post obstruction
21
Q

Discuss the morphology of reversible injury:

A

Cellular swelling:
Failure of ion pumps in plasma membrane
Organ level: pallor, increased weight
Microscopic: hydropic change or vacuolar degeneration

Fatty change:
Hypoxic, toxic, or metabolic injuy
Lipid vauoles in cytoplasm (cardiac or hepatocytes)

Ultrastructural:
blebbing, mitochondia, ER dilation

22
Q

What happens with the aging process to the cells that can be pathological:

A

Telomere shortening (wear and tear, stem cells//RNA repair)

23
Q

What is apoptosis mediated by? Describe how this mediator is activated:

A

** Apoptosis is mediated by caspases which activates proteases break down the cytosketeon and endunucleases breakdown DNA**

Caspases activation:
Intrinsic mitochondrial pathway: cellular injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2
** cytochrome C resides in inner mitochondrial matrix, Bc12 (regulates cytochrome C) gets knocked out then cytochrome C can leak out and activate caspases driving apoptosis **

Extrinsic receptor ligand pathway: something is binding to the outside of the cell

example: FAS ligand binds FAS death receptor (CD95) - T cells born in the bone and goes the thymus to get educated and gets tested: (+) selection - Do you have the ability to bind self-antigen and MHC; (-) selection to strongly binding self-antigen, if yes it is destroyed

Cytotoxic CD8+ T cell mediated pathway: recognizes antigen and secretes perforins, granzyme from CD8+T enters pores and activates caspases