Pathology - Cell Injury Flashcards

1
Q

What is apoptosis and describe the stimuli and features

A
  • programmed cell death, removes unwanted cells and stops excess growth
    –cell dies by internal suicide program
  • 2 phases: initiation phase (via intrinsic and extrinsic pathway) and execution phase
    causing protein breakdown by caspases
  • plasma membrane remains intact and does not involve inflammation, cell becomes target for phagocytosis

features:
cells shrinkage
no inflammation
chromatin condensation, fragmentation, cell blebbing, phagocytosis
stimuli: embryogenesis, hormone dependent involution, DNA damage, developmental atrophy, post inflammation

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2
Q

What happens at the cellular level in apoptosis

A
cell shrinkage
chromatin condensation
fragmentation
formation of blebs
phagocytosis by macrophages
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3
Q

Describe the mechanisms involved in apoptosis

A

1) Initiation phase
- intrinsic pathway = mitochondrial permeability increased, causes cytochrome c release, activates caspases
- extrinsic pathway = activation of death receptors (TNF family) causing activation of caspases (protease enzymes)

2) Execution phase
- caspases act on cell components causing protein degradation, removal of dead cells by phagocytosis

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4
Q

Describe the cellular changes in necrosis

A
  • cellular swelling, eosinophilia, myelin figures, nuclear changes (pyknosis, karyolysis, karyorrhexis)
  • organelle disruption, cell rupture, inflammation
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5
Q

What are the patterns of tissue necrosis

A
  • coagulative: characterised by protein denaturation, architecture preserved, common after MI
  • liquefactive: characterised by enzymatic digestion, common after CNS hypoxia
  • caseous: exhibits coagulation and liquefaction, seen in Tb
  • fat: characterised by lipase activation
  • fibrinoid: due to antigen-antibody complex deposition in blood vessel walls
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6
Q

What happens inside cells when they are injured (damage that occurs after severe ischaemia)

A
  • depletion of ATP: causes failure of ion pumps and cell swelling
  • mitochondrial damage: causes leaking of cytochrome c leading to apoptosis
  • increased intracellular calcium: causes activation of phospholipase which degrades membrane phospholipids
  • accumulation of oxygen-derived free radicals: causes damage to DNA and RNA
  • defects in membrane permeability: effects intracellular osmolarity and enzyme activity
  • damage to DNA and protein: leads to activation of apoptosis
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7
Q

What are the morphological and chemical changes associated with early cell injury

A

morphological: cell swelling, membrane blebbing, chromatin clumping, ribosomes detach from ER
chemical: depletion of ATP, failure of Na+/K+ATPase, increased intracellular Ca+2, generation of free radicals

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8
Q

What is a free radical and what are their pathologic effects

A

unstable, partially reduced molecules with unpaired electrons in the outer orbit
causes necrosis or apoptosis

effects: lipid peroxidation, oxidation of proteins, DNA lesions

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9
Q

What are the stages of ischaemic cell injury

A
  • reversible: cell swelling, membrane blebbing, nuclear chromatin clumping, ribosome detachment from ER
  • irreversible: nuclear pyknosis/karyorrhexis/karyolysis, lysosome rupture, mitochondrial vacuolisation
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10
Q

Describe the sequence of events in reversible ischaemia

A
  • initially reduced oxidative phosphorylation causing reduced ATP production
  • failure of Na+/K+ pump, cause increased intracellular Na+ and decreased K+ and cellular swelling
  • failure of Ca+2 pump, cause increased intracellular Ca+2 which activates phospholipase (degrades membranes)

features: cellular swelling, membrane blebbing, nuclear chromatin clumping, ribosomes detach from ER

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11
Q

What are the phenomena that characterise irreversible cell injury

A

inability to reverse mitochondrial dysfunction and development of profound disturbances in membrane function

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12
Q

What are the morphological features of irreversible ischaemia

A

nuclear destruction
lysosomal rupture
severe mitochondrial vacuolization
death by necrosis or apoptosis

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13
Q

What are some examples of proteins that leak across a degraded cell membrane

A

cardiac (creatinine kinase and troponin)
bile duct epithelium (alkaline phosphatase)
hepatocytes (transaminases)

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14
Q

Describe reperfusion injury

A
  • increased injury to ischaemic cells with restoration of perfusion
  • due to generation of reactive oxygen and nitrogen species
  • activation of inflammatory/complement cascades
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15
Q

What is atrophy and what are the causes and mechanisms

A
  • decrease in cell size and number, may be physiological or pathological
    causes: decreased workload, denervation, reduced blood flow, inadequate nutrition, loss of endocrine stimulation
    mechanisms: decreased protein synthesis or increased protein degradation (mainly by ubiquitin-proteasome path)
    examples: fracture disuse, damage to nerves causing muscle atrophy, reproductive organs from lack of estrogen
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16
Q

What is hyperplasia and what are the types

A

increase in the number of cells

physiologic: hormone (breast size in puberty), compensatory (post partial hepatectomy)
pathologic: excess hormone (BPH), viral infection (papillomavirus)

17
Q

What are the cellular mechanisms of physiological hyperplasia

A

increased growth factor production
increased growth factor receptors
activation of intracellular signalling

18
Q

What are the clinical features of BPH

A

increased frequency, nocturia, difficulty starting and stopping stream, dribbling, dysuria, increased infections

19
Q

What are some features of diffuse toxic hyperplasia of the thyroid gland (graves disease)

A

tachycardia, palpitations, heart failure, eye staring, lid lag, proptosis, malabsorption, diarrhoea, tremor, anxiety

20
Q

What is hypertrophy and what are the types

A

-increase in the size of a cell due to synthesis of structural components

  • physiologic: increase in size of breast during lactation and uterus during pregnancy, skeletal muscle with exercise
  • pathologic: heart in chronic hypertension
21
Q

What is metaplasia and describe the mechanism, some examples and what are possible outcomes

A
  • replacement of one normal cell type with another normal cell type, reversible and may be adaptive or pathological
    mechanism: reprogramming of cells involving signals from cytokines, growth factors, genes, ect
    examples: squamous to columnar in barrett esophagus, columnar to squamous in smoking (most common)
    outcomes: reversibility, ongoing, malignant transformation
22
Q

What are the 2 different forms of pathological calcification and give an example of each

A
  1. Dystrophic calcification = arises in non-viable tissue in presence of normal calcium levels
    - example: arteries in atherosclerosis
  2. Metastatic calcification = arises in viable tissue in setting of hypercalcaemia
    - example: gastric mucosa, pulmonary calcinosis, nephrocalcinosis
23
Q

What are the causes of hypercalcaemia (what are the causes of metastatic calcification)

A
  • increased PTH secretion: hyperparathyroidism
  • destruction of bone tissue: skeletal metastasis
  • vitamin D related disorders: sarcoidosis
  • renal failure: secondary hyperparathyroidism
24
Q

What is steatosis and what are causes of hepatic steatosis

A
  • the abnormal accumulation of TAG within parenchymal cells due to excessive entry or defective metabolism
  • can occur in: heart muscle, kidney, liver, skeletal muscle
  • cause of hepatic steatosis: alcohol, toxins, protein malnutrition, diabetes, obesity