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Cells to Systems > Cellular responses to injury > Flashcards

Cellular responses to injury Flashcards

1
Q

What is meant by the term cell degeneration?

A

Sublethal injury (reversible)

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2
Q

What is meant by the term hydropic degeneration?

A

Intracellular accumulation of water due to an inability to regulate entry and exit of water and ions

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3
Q

What are the two major causes of hydropic degeneration?

A
  1. Physical damage to plasma or organelle membranes

2. Insufficient energy to fuel sodium potassium pump (hypoxia)

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4
Q

What is meant by the term fatty change? (lipidosis, steatosis or fatty degeneration)

A

Intracellular accumulation of excess lipid

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5
Q

Which cells are most susceptible to lipidosis?

A

Cells that normally metabolise a lot of lipid, such as hepatocytes or renal tubular epithelial cells

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6
Q

What is the most common type of fatty acids which accumulate in hepatocyte cytoplasms

A

Triglycerides, this is because the packaging of triglycerides with apoproteins into VLDL’s is highly energy demanding

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7
Q

What are some causes of hepatic lipidosis?

A
  1. Excess entry of fatty acids into the liver
  2. Inadequate supply of proteins or cofactors for synthesis of apoproteins
  3. Sublethal hypoxia
  4. Sublethal toxic injury
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8
Q

What are some causes of excess intra-cellular storage of glycogen?

A
  1. Excess circulating glucose (dietary)
  2. Steroid hepatopathy
  3. Diabetes mellitus
  4. Inherited glycogen storage disorders
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9
Q

What cells is glycogen normally stored?

A
  1. Skeletal myocytes

2. Hepatocytes

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10
Q

What is the pathogenesis of steroid hepatopathy?

A

Hyperadrenocortism due to an adrenal cortex tumour or excessive use of corticosteroids. Excess production of glucocorticoids induce transcription of glycogen synthetase, resulting in excessive storage of glycogen in hepatocytes.

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11
Q

What is lysosomal storage disorders?

A

Conditions in which substrates derived from normal cell catabolism accumulate within lysosomes rather than being degraded by lysosomal enzymes

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12
Q

When do lysosomal storage disorders usually manifest?

A

Lysosomal storage disorders are generally inherited, most commonly manifesting in the first few months of life

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13
Q

Which cells are most vulnerable to accumulation of indigestible substrates?

A

Neurons and myocardial fibres, this is because they are permanent cells, unable undergo mitotic division after birth. Therefore, the indigestible substrates continue to accumulate, resulting in cell dysfunction

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14
Q

What is amyloid?

A

An insoluble, extracellular, fibrillar glycoprotein deposit.

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15
Q

Can LSD be acquired?

A

Yes, particularly from the ingestion of the indolizidine alkaloid swainsonine

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16
Q

What is amyloidosis?

A

Disease resulting from localised or generalised (systematic) tissue deposition of amyloid

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17
Q

What are three extracellularly mediated mechanisms of cellular degeneration?

A
  1. Amyloidosis
  2. Fibrinoid change
  3. Collagenolysis
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18
Q

What makes amyloid resistant to enzymatic degradation?

A

Formation of beta-pleated sheets (structural)

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19
Q

What is the most common type of amyloid in domestic animals?

A

Serum amyloid A (AA), an insoluble fragment of acute phase protein normally produced by the liver and found in circulating blood

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20
Q

Do animals with increased blood concentrations of SAA develop amyloidosis?

A

No!!

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21
Q

What is the most common cause of amyloidosis?

A

Increase synthesis and release of SAA in response to active inflammation or tissue damage

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22
Q

What causes cats to develop IAPP amyloid?

A

Type 2 diabetes mellitus resulting in deposits of amyloid in the pancreatic islets of Langerhans

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23
Q

What is TSE?

A

Transmissible spongiform encephalopathies, in which amyloid deposits composed of miss-folded proteins may develop

24
Q

What are the effects of amyloid deposition?

A
  1. Can cause physical compression of adjacent cells and compromised vascular perfusion resulting in atrophy, cell degeneration or cell death
  2. Risk of spontaneous liver rupture
  3. Increased glomerular permeability resulting in hypoprotinaemia
25
Q

What is fibrinoid change?

A

An extracellular degenerative phenomenon observed in damaged blood vessels. Damage to vascular endothelium of blood vessels results in the infiltration of plasma proteins, including fibrin.

26
Q

Can fibrinoid change be seen macroscopically?

A

No, but associated thrombosis, haemorrhage and oedema may be seen grossly.

27
Q

What could cause fibrinoid change?

A

Damage to endothelial cells due to circulating toxins, such as E. coli in pigs.

28
Q

What is collagenolysis?

A

lysis of collagen fibrils (…pretty self explanatory)

29
Q

What causes collagenolysis?

A

Proteolytic enzymes such as collagenase released from cells such as eosinophils and neutrophils

30
Q

What is meant by the term necrosis?

A

Death of cells in a living organism and the gross microscopic morphological changes that are indicative of this event

31
Q

What are the two major types of necrosis?

A
  1. Oncotic

2. Apoptosis

32
Q

Describe oncotic necrosis

A

Cell death via swelling

33
Q

Describe apoptosis

A

Cell death via shrinking

34
Q

Which form of necrosis (oncosis or apoptosis) is more common?

A

Oncotic necrosis

35
Q

Is apoptosis grossly visible?

A

No, because it only involves individual cells or small clusters of cells

36
Q

Describe the mechanism of apoptosis

A

Activated caspase cleave cytoskeletal proteins and active endonuclease to cleave nuclear proteins involved in DNA replication, repair and transcription, ultimately resulting in cell death.

37
Q

Does apoptosis stimulate the inflammatory response?

A

No, there is no release of pro-inflammatory mediators and cell debris is rapidly phagocytosed by neighbouring cells

38
Q

Does oncotic necrosis stimulate the inflammatory response?

A

Yes, products released by phospholipid degradation, such as arachidonic acid are chemoattractants for leukocytes.

39
Q

What is required for a cell to be irreversibly injured

A

Severe membrane damage or severe mitochondrial damage

40
Q

What is a pivotal biochemical change that triggers cell death by oncotic necrosis?

A

Influx of calcium due to direct injury to the membrane or failure of membrane ion pumps. Free intracellular calcium can activate phospholipases, ATPases, proteases and endonuclease.

41
Q

How are cells which have undergone oncotic necrosis cleared?

A

Cells are degraded by hydrolytic lysosomal enzymes. Autolysis by the dead cells themselves and heterolysis by recruited leukocytes

42
Q

Is oncotic necrosis grossly visible?

A

Yes, due to the sheer number of cells which are affected

43
Q

What is meant by pyknosis?

A

Shrunken, darkly staining nucleus due to chromatin condensation

44
Q

What is meant by karyolysis?

A

Fading of the nucleus leading to eventual disappearance

45
Q

What is meant by haryorrhexis?

A

Rupture of the nuclear envelope with extrusion of dark nuclear fragments

46
Q

What is meant by the term coagulative necrosis?

A

Lethal hypoxic or anoxic insults resulting in denaturation of both structural and enzymatic proteins, preventing proteolysis of the dead cells.

47
Q

What are some common causes of coagulative necrosis?

A

Exotoxins of anaerobic bacteria, such as clostridium species or Fusobacterium necrophorum

48
Q

What is meant by the term liquefactive necrosis?

A

Rapid enzymatic degradation of dead cells (both autolysis and heterolysis), resulting in obliteration of tissue architecture and formation of liquid

49
Q

What are some common causes of liquefactive necrosis?

A

Pyogenic bacteria, such as staphylococci and streptococci

50
Q

What is meant by the term caseous necrosis?

A

Dead tissue that is converted into a grossly dry, granular, friable coagulum.

51
Q

What are some common causes of caseous necrosis?

A

Chronic liquefactive abbesses or bacteria with complex cell walls and poorly degradable lipid components, such as tuberculosis and corynebacterium

52
Q

What is meant by fat necrosis?

A

Necrosis of fat cells only! (don’t mind if I do…)

53
Q

What are some common causes of fat necrosis?

A
  1. Liplytic enzymes
  2. Trauma
  3. Reactive oxygen species
  4. Hypoxia
54
Q

What is meant by dystrophic mineralisation?

A

Deposition of calcium salts in tissues that have undergone oncotic necrosis, even when blood calcium levels are normal

55
Q

What is meant by metastatic mineralisation?

A

Deposition of calcium salts in tissues that due to elevated blood calcium levels

56
Q

What is dry gangrene?

A

Coagulative necrosis induced ischaemia, such as frostbite

57
Q

What is wet gangrene?

A

Necrosis of tissue that is then colonised by bacteria, resulting in liquefaction and putrefaction (rotting)

Cells to Systems (10 decks)

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