Cell Injury and Death Flashcards

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1
Q

List 4 factors which contribute to the maintenance of a cellular steady state

A
  1. Preservation of genetic integrity 2. Normal enzyme content 3. Intact membranes and transmembrane proteins Adequate supply of substrates and oxygen
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2
Q

Define ‘Cell Injury’

A

A biochemical and/or morphological change which occurs when the steady state is perturbed by adverse influences

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3
Q

What do each of these prefixes or suffixes mean? Ana- Dys- Hyper- Hypo-

A

Ana- = ‘without’ Dys- = ‘disordered’ Hyper- = ‘extreme or beyond normal’ Hypo - = ‘Below normal’

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4
Q

What do each of these prefixes or suffixes mean? Meta- -itis -oma -osis

A

Meta- = ‘change’ -itis = ‘inflamed’ -oma = ‘tumour’ -osis = ‘ condition, disease or increase’

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5
Q

What do these suffixes mean? -oid -penia -cytosis -ectasis -plasia -opathy

A

-oid = ‘resemblance’ -penia = ‘deficiency’ -cytosis = ‘increase in cell number’ -ectasis = ‘dilatation’ -plasia = ‘formation’ -opathy = ‘denoting disease or disorder’ (governed by the prefix i.e. ‘neuropathy’ - a disease of the peripheral nerves

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6
Q

List 4 common causes of cell injury

A

Oxygen availability Physical Trauma Chemical Agents Infectious organisms Irradiation Immunological Genetics Ageing

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7
Q

What is the difference between hypoxia and anoxia and what is the common cause of both?

A

Hypoxia is a reduction in the availability of oxygen Anoxia is the complete loss of oxygen delivered to cells Common cause is ischaemia

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8
Q

What is the danger with radical re-oxygenation of tissues?

A

Reperfusing tissues can generate oxygen free radicals and further cause damage

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9
Q

Explain the mechanism of cyanide poisoning

A

Primary effect of cyanide poisoning is impairment of oxidative phosphorylation. This is catalysed by the cytochrome oxidase enzyme system in the mitochondria, and the impairment arises from the inhibition by cyanide of cytochrome oxidase

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10
Q

What are the consequences of mechanical trauma?

A

Disruption of cell structure Thrombosis leading to ischaemia

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11
Q

Which product is toxic in the breakdown of paracetamol?

A

NAPQI N-Acetyl-P-Benzo-Quinone Imine

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12
Q

What is the treatment for paracetamol poisoning?

A

Administer activated charcoal (AC) if the patient is alert and presents, ideally, within 1 hour post ingestion. The IV formulation of NAC (Acetate) is commonly used in many institutions for the treatment of acetaminophen ingestion in more severe cases

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13
Q

What are the two secretions from bacteria which are toxic?

A

Endo- and Exo- toxins

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14
Q

Briefly describe the mechanism of ionisation to the tissue

A

Generation of free radicals causing direct damage to macro molecules following exposure to a source such as UV light

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15
Q

Give 3 examples of tissues which have a high sensitivity to ionising radiation

A

Bone marrow Gonads Intestines

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16
Q

Give 3 examples of tissues which have a low sensitivity to ionising radiation

A

Uterus Pancreas Adrenal

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17
Q

What makes certain cells more sensitive to ionising radiation than others?

A

The most sensitive cells are those that are undifferentiated, well nourished, dividing quickly and highly active metabolically.

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18
Q

List the targets of cell injury

A

Mitochondrial function Membrane integrity and function Protein synthesis Cytoskeleton Genetic apparatus

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19
Q

Describe this flow chart

A

Diminished oxidative phosphorylation and reduced ATP levels

  • Activity of plasma membrane ATP-driven “sodium pump” is reduced, with consequent influx of sodium and calcium, leading to isosmotic gain of water and acute cellular swelling
  • Anaerobic glycolysis increases to generate ATP from glycogen, which depletes glycogen stores and results in accumulation of lactic acid thus lowering the intracellular pH
  • Decreasing pH and ATP levels cause ribosomes to detach from rough endoplasmic reticulum and reduction in protein synthesis
  • Note that all these effects are potentially reversible, and the restoration of blood flow eventually allows the cell to recover normal function.
  • Cellular swelling or acute cellular oedema is usually associated with hypoxia, but may also occur with fever or damage due to toxins
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20
Q

What is the treatment for free radical toxicity?

A

Detoxification by superoxide dismutase and antioxidants like vitamins A, C and E

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21
Q

Name 3 factors can cause membrane defects?

A

Bacterial toxins

Viral proteins

Complement

Cytolytic Lymphocytes

Various physical and chemical agents

22
Q

What can an iincrease in calcium into the cell cause?

A

Activates a number of enzymes with potential deleterious cellular effects:

ATPases

Phospholipases

Proteases

Endonucleases

23
Q

What is the function of an ATPase enzyme?

A

ATPases transport a variety of different compounds, like ions and phospholipids, across a membrane using ATP hydrolysis for energy. An increased activation of ATPase would hesten ATP depletion

24
Q

What is the function of a phospholipase enzyme?

A

Hydrolyses phospholipds into fatty acids. Increased activation of these enzymes will lead to membrane damage

25
Q

What is the function of a protease enzyme?

A

Breaks down proteins into amino acids. Increased amounts of proteases will break down membrane and cytoskeletal proteins

26
Q

What is the function of an endonuclease?

A

Recognize and ‘cut’ at specific points in DNA

27
Q

When does cell death occur?

A

When cells are unable to achieve a new steady state following environmental insults

28
Q

What is the general reason for cell death?

A

Due to irreversible breakdown of energy dependant organised interactions between DNA, membranes and enzymes

29
Q

What are the two types of cell death and what is the key difference between the two?

A

Necrosis and Apoptosis

Key difference: Apoptosis is active and programmed. Necrosis is passive and unprogrammed

30
Q

Which type of necrosis is the most common?

A

Coagulative Necrosis

31
Q

Name the 4 main types of necrosis

A

Coagulative

Caseous

Colliquative

Gangrene

32
Q

What is coagulative necrosis and what are its characteristics?

A

Denaturation of intracytoplasmic protein

The dead tissue becomes firm and swollen

Tissue shows retention of microscopic architecture

Typical of ischaemic injury (except in the brain)

Cellular proteins may leak into the blood

33
Q

What is colliquartive necrosis and what are its characteristics?

A

Necrosis of brain tissue

Total liquefaction and the site is eventually marked by a cyst

The brain unergoes this type of liquefaction because it does not have a collagenous framework

34
Q

What is caseous necrosis and what are its characteristics?

A

Form of cell death in which the tissue maintains a cheese-like appearance

Characteristic of TB

Cheese like

Cellular detail in the area of necrosis is destroyed and surrounded by granulamtous inflammation

35
Q

What is gangrenous necrosis and what are its characteristics?

A

A type of necrosis caused by a critically insufficient blood supply

Can be dry, wet, gaseous or other

36
Q

Name 3 physiological examples of apoptosis

A

Embryogenesis

Involution

Elimination of self reacting lymphocytes

37
Q

Give 3 examples of pathological apoptosis

A

DNA/Protein damage

Viral infections

Cell killing by cyto T cells

38
Q

What does this diagram represent?

A

The mechanisms of Apoptosis

39
Q

Which factors required for Apoptosis are sequestered in the mitochondria and what do these molecules activate when released into the

A

Apoptosis Initiating Factor (AIF) and CytoC

Activate caspases in the cytosol

40
Q

What are the effector molecules of apoptosis and what are they activated by?

A

Caspases

Activated by the presence of CytoC and AIF in the cytosol

41
Q

What is the colloqueal name for P53?

A

‘The Gaurdian of the Genome’

42
Q

What is P53 activated by and what does it cause upon activation?

A

DNA damage

Causes the elimation of damaged cells by apoptosis

43
Q

When are mutations of P53 very common?

A

In malignant tumours

44
Q

How does BCL2 inhibit apoptosis

A

Sequesters CytoC

45
Q

Which of necrosis or apoptosis is physiologic and which is pathologic?

A

Necrosis = Patho

Apoptosis = Physio

46
Q

Is the plasma membrane intact or disrupted during apoptosis?

A

Intact in apoptosis

Disrupted in necrosis

47
Q

What is the staging of the nucleus in apoptosis?

A

Fragmentation to Apoptotic Bodies

48
Q

What is the staging of the nucleus in Necrosis?

A

Pyknosis to Karyorrhexis to Karyolysis

49
Q

Does necrosus feature adjacent inflammation?

A

Yes, frequently

It is not present in apoptosis

50
Q

What is the state of the cell size in necrosis and apoptosis?

A

Enlarged in necrosis

Reduced in apoptosis