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Semester 2 - PathPro > 2. Cell Injury and death > Flashcards

2. Cell Injury and death Flashcards

1
Q

What can severe changes in environment lead to?

A

• All cells have effective mechanisms to deal with mild
changes in environmental conditions.
• More severe changes in environment lead to cell adaptation, injury or cell death.

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2
Q

What does the degree of injury depend on?

A

Degree of injury depends on:
– Type of injury
– Severity of injury
– Type of tissue.

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3
Q

What kind of things can cause cell injury?

A
  • Hypoxia -oxygen deprevation
  • Toxins - alcohol, drugs, insecticides
  • Physical agents
  • Radiation
  • Micro-organisms - bacteria, virus, fungi, parasites
  • Immune mechanisms
  • Dietary insufficiency and deficiencies, dietary excess
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4
Q

Give examples of physical agents that cause cell injury

A
  • Direct trauma (crush, incision,laceration etc)
  • Extremes of temperature (burns, frostbite, hypothermia)
  • Changes in pressure
  • Electric currents
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5
Q

What is the cell injury response?

A
  • Homeostasis
  • Cellular adaptation
  • Cellular injury
  • Cell death
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6
Q

What things are toxic?

A
  • Glucose and salt in hypertonic solutions
  • high O2 concentration
  • poisons
  • pollutants
  • insecticides
  • herbicides
  • asbestos
  • alcohol
  • narcotic drugs
  • medicines
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7
Q

What are the 4 types of hypoxia?

A
  1. Hypoxaemic hypoxia - – arterial content of oxygen is low
  2. Anaemic hypoxia – decreased ability of haemoglobin to carry oxygen
  3. Ischaemic hypoxia - interruption to blood supply
  4. Histiocytic hypoxia – inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes
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8
Q

What causes Hypoxaemic hypoxia?

A
  • Reduced inspired p02 at altitude - There’s reduced concentration of oxygen in the surroundings of the individual.
  • Reduced absorption secondary to lung disease
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9
Q

What causes Anaemic hypoxia?

A
  • Anaemia

* Carbon monoxide poisoning

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10
Q

What causes Ischaemic hypoxia?

A
  • Blockage of a vessel

* Heart failure

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11
Q

What causes Histiocytic hypoxia?

A

• Cyanide poisoning

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12
Q

What is the difference between hypoxia and ischaemia?

A

hypoxia - oxygen deprivation
ischaemia - loss of blood supply to a particular organ or tissue so not only loss of oxygen but also other substrates like glucose. Ischaemia will have a more rapid change and cause more sever injury

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13
Q

How long can neurones and fibroblasts survive during hypoxia?

A

Neurones = few minutes Fibroblasts = few hour

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14
Q

Give a summary of hypoxic cell injury

A
  1. Cell is deprived of oxygen.
  2. Mitochondrial ATP production stops.
  3. The ATP-driven membrane ionic pumps run down e.g Na/K+ pump.
  4. Sodium and water seep into the cell.
  5. The cell swells, and the plasma membrane is stretched.- oncosis
  6. Glycolysis enables the cell to limp on for a while.
  7. The cell initiates a heat-shock (stress) response (see below), which will probably not be able to cope if the hypoxia persists.
  8. The pH drops as cells produce energy by glycolysis and lactic acid accumulates - which can cause clumping of nuclear chromatin.
  9. Calcium enters the cell.
  10. Calcium activates:
    • phospholipases, causing cell membranes to lose phospholipid,
    • proteases, damaging cytoskeletal structures and attacking membrane proteins,
    • ATPase, causing more loss of ATP,
    • endonucleases, causing the nuclear chromatin to clump.
  11. The ER and other organelles swell.
  12. Enzymes leak out of lysosomes and these enzymes attack cytoplasmic components.
  13. All cell membranes are damaged and start to show blebbing.
  14. At some point the cell dies, possibly killed by the burst of a bleb.

1 - 9 - reversible
10 - 14 - irreversible - prolonged hypoxia

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15
Q

What can cause Ischaemia-Reperfusion Injury?

A

If blood flow is returned to a tissue which has been subject to ischaemia but isn’t yet necrotic, sometimes the tissue injury that is then sustained is worse than if blood flow was not restored. It may be due to:
• Increased production of oxygen free radicals with
reoxygenation as a result of a burst of mitochondrial activity.
• Increased number of neutrophils following reinstatement of blood supply resulting in more inflammation and increased tissue injury.
• Delivery of complement proteins and activation of the complement pathway.

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16
Q

What are hypersensitivity reactions?

A

Hypersensitivity reactions - host tissue is injured secondary to an overly vigorous immune reaction, e.g., urticaria (= hives)

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17
Q

Besides hypoxia, how else can the cell be injured?

A

Limited responses to injuries so similar outcomes to hypoxia.

Attack different key structures - mainly membranes (eg radicals)

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18
Q

What are autoimmune reactions?

A

Autoimmune reactions - immune system fails to distinguish self from non-self, e.g., Grave’s disease of thyroid.

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19
Q

What are free radicals?

A

• = reactive oxygen species
• Single unpaired electron in an outer orbit – an
unstable configuration hence react with other molecules, often producing further free radicals

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21
Q

What are the 3 free radicals of biological significance?

A

• OH• (hydroxyl) - the most dangerous
•O2- (superoxide
• H2O2
(hydrogen peroxide)

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22
Q

When are free radicals produced?

A
  1. Normal metabolic reactions: e.g., oxidative
    phosphorylation
  2. Inflammation: oxidative burst of neutrophils
  3. Radiation: H2O –> OH•
  4. Contact with unbound metals within the body: iron
    (by Fenton reaction) and copper
    • Free radical damage occurs in haemachromatosis and
    Wilson’s disease
  5. Drugs and chemicals: e.g., in the liver during metabolism of paracetamol or carbon tetrachloride
    by P450 system
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23
Q

How does the body control free radicals?

A
  1. Anti-oxidant scavengers: donate electrons to the free radical
  2. Metal carrier and storage proteins (transferrin, ceruloplasmin): sequester iron and copper
  3. Enzymes that neutralise free radicals
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24
Q

Give the cell components most susceptible to injury

A

There are four essential cell components that are the principal targets of cell injury:

  1. Cell membranes
  2. Nucleus
  3. Proteins - structural proteins and enzymes
  4. Mitochondria
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25
Q

Give 3 examples of Anti-oxidant scavengers

A

vitamins A, C and E

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26
Q

What do injured and dying cells look like under a light microscope?

A

In hypoxia:
•Cytoplasmic changes - swollen, cytoplasm less pink and more watery looking

  • Nuclear changes - pyknosis, Karyorrhexis, Karyolysis
  • Abnormal cellular accumulations
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27
Q

How do free radicals injure cells?

A

• If the number of free radicals overwhelms the anti-
oxidant system = oxidative imbalance
• Most important target are lipids in cell membranes.
– Cause lipid peroxidation.
– This leads to generation of further free radicals → autocatalytic chain reaction.
• Also oxidise proteins, carbohydrates and DNA
– These molecules become bent out of shape,
broken or cross-linked
– Mutagenic and therefore carcinogenic

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28
Q

Give 3 examples of Enzymes that neutralise free radicals

A

– Superoxide dismutase
– Catalase
– Glutathione peroxidase

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29
Q

What are free radicals?

A

Free radicals are reactive oxygen species. They have a single unpaired electron in an outer orbit. This is an unstable configuration and because of this free radicals react with other molecules, often producing further free radicals

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30
Q

What are heat shock proteins , give their function and provide an example

A
  • Heat shock proteins are another way in which the cell protects itself against the effects of injury.
  • Examples include stress proteins, unfoldases, chaperonins.
  • Heat shock or the cellular stress response is triggered by any form of injury, not just heat.
  • All cells when submitted to stress turn down their usual protein synthesis and turn up the synthesis of HSPs.
  • HSPs are important in cell injury as the heat shock response aims to ‘mend’ misfolded proteins and maintain cell viability and thus maximising cell survival.
  • One example of a HSP is ubiquitin.
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31
Q

What do injured and dying cells look like under an electron microscope?

A

Reversible:
• Swelling – both of the cell and the organelles due to Na+/K+ pump failure
• Cytoplasmic blebs, which are symptomatic of cell swelling
• Clumped chromatin due to reduced pH
• Ribosome separation from the endoplasmic reticulum due to the failure the of energy-dependant process of maintaining ribosomes in the correct location

Irreversible:
• Increased cell swelling
• Nuclear changes - pyknosis, karyolysis, or karyorrhexis
• Swelling and rupture of lysosomes – reflects membrane damage
• Membrane defects
• The appearance of myelin figures (which are damaged membranes)
• Lysis of the endoplasmic reticulum due to membrane defects
• Amorphous densities in swollen mitochondria

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32
Q

Define the following terms

  1. Pyknosis
  2. Karyolysis
  3. Karyorrhexis
A
  1. Pyknosis- Shrinkage of nucleus
  2. Karyorrhexis - Fragmentation of nucleus
  3. Karyolysis - Complete disintegration of nucleus
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33
Q

When does Abnormal cell accumulations occur?

A
  • Seen when metabolic processes become deranged

* Often occur with sublethal or chronic injury

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34
Q

Are abnormal cell accumulations reversible?

A
  • Can be reversible

* Can be harmless or toxic

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35
Q

Where do these abnormal cell accumulations come from?

A

They can derive from the:
• Cell’s own metabolism
• The extracellular space, e.g., spilled blood
• The outer environment, e.g., dust

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36
Q

What are the five main groups of intracellular accumulations?

A
  • Water and electrolytes
  • Lipids – triglycerides and cholesterol
  • Proteins – e.g., Mallory’s hyaline, alpha-1 antitrypsin
  • ‘Pigments’ – exogenous and endogenous
  • Carbohydrates
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37
Q

When does fluid accumulate in cells?

A
  • Hydropic swelling
  • Occurs when energy supplies are cut off, e.g., hypoxia
  • Indicates severe cellular distress
  • Na+ and water flood into cell
  • Particular problem in the brain
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38
Q

Define steatosis

A
  • accumulation of triglycerides
  • Often seen in liver (major organ of fat metabolism)
  • If mild - asymptomatic
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39
Q

What are the causes of lipids accumulating in cells?

A
  • Alcohol (reversible in about 10 days)
  • Diabetes mellitus
  • Obesity
  • Toxins (e.g., carbon tetrachloride)
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40
Q

What happens when there is excess cholesterol (lipid) accumulated in cells? What forms?

A

Cholesterol:
• Cannot be broken down and is insoluble
• Can only be eliminated through the liver
• Excess stored in cell in vesicles
• Accumulates in smooth muscle cells and macrophages in atherosclerotic plaques = foam cells
• Present in macrophages in skin and tendons of people with hereditary hyperlipidaemias = xanthomas

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41
Q

Give two examples of Accumulation of exogenous pigment in cells

A

• Carbon/coal dust/soot – urban air pollutant
• Inhaled and phagocytosed by alveolar macrophages
• Leads to Anthracosis and blackened peribronchial lymph nodes
• Usually harmless, unless in large amounts = fibrosis
and emphysema = coal worker’s pneumoconiosis

  • Tattooing – pigments pricked into skin
  • Phagocytosed by macrophages in dermis and remains there
  • Some pigment will reach draining lymph nodes producing darkened lymph nodes
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42
Q

How does protein accumulation in cells present visually?

A

These accumulations can be seen as eosinphil droplets or aggregations in the cytoplasm.

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43
Q

Give and explain 2 conditions that can cause the accumulation of proteins in cells

A

Alcoholic liver disease:
• Mallory’s hyaline (damaged keratin filaments)

α1-antitrypsin deficiency:
• Liver produces incorrectly folded α1-antitrypsin protein (a protease inhibitor)
• Cannot be packaged by ER, accumulates within ER and is not secreted
• Systemic deficiency – proteases in lung act unchecked
resulting in emphysema

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44
Q

Give an example of Accumulation of endogenous pigment in cells

A

Haemosiderin:
•Iron storage molecule
•Derived from haemoglobin, yellow/brown
• Forms when there is a systemic or local excess of iron, e.g., bruise
•With systemic overload of iron, haemosiderin is deposited in many organs = haemosiderosis
• Seen in haemolytic anaemias, blood transfusions and hereditary haemochromatosis

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45
Q

What is hereditary haemochromatosis?

A
  • Genetically inherited disorder - results in increased intestinal absorption of dietary iron
  • Iron is deposited in skin, liver, pancreas, heart and endocrine organs - often associated with scarring in liver (cirrhosis) and pancreas.
  • Was called ‘bronze diabetes’
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46
Q

What are the symptoms of hereditary haemochromatosis?

A
  • liver damage
  • heart dysfunction
  • multiple endocrine failures, especially of the pancreas
47
Q

What is the treatment for hereditary haemochromatosis?

A

Treatment is repeated bleeding

48
Q

how is bilirubin produced?

A

Bilirubin is produced from the breakdown of haem from haemoglobin (breakdown of porphyrin rings). Formed in all cells of body (cytochromes contain heme)

49
Q

How is bilirubin eliminated?

A

Bilirubin is eliminated in bile.

It’s taken from body tissues by albumin to the liver, here it’s conjugated and excreted in bile.

50
Q

What causes jaundice?

A
  • Jaundice is the accumulations of bilirubin .

* It occurs if bile flow is obstructed or overwhelmed, bilirubin in the blood rises and jaundice occurs.

51
Q

What does jaundice look like?

A

You get a bright yellow colouring of the skin and sclera.

52
Q

List the systemic and local effects of molecule leakage

A
  • Can cause local inflammation
  • May have general toxic effects on body
  • May appear in high concentrations in blood and can aid in diagnosis
53
Q

Give the 3 main molecules that can leak out of membranes

A
  • Potassium
  • Enzymes
  • Myoglobin
54
Q

Describe Potassium leakage when the membranes are leaky, including what conditions it can lead to and the treatment

A
  • When damage occurs to the cell and to the cell membrane, It can result in the release of K+ into the extracellular space - hyperkalemia.
  • This can be particularly harmful as it causes an electrolyte imbalance, this can bring on conditions such as cardiac arrhythmia and sudden death.
  • Given fluids to lower potassium levels
55
Q

Describe Enzyme leakage

A

Enzymes such as Creatine kinase, AST (liver enzyme), troponin potterns (C, T, I) can leak out of the cell. They can be used to identify the site of damage within the body.

56
Q

Who are particularly vulnerable to potassium leakage?

A

people undergoing chemotherapy as massive amounts of tumour necrosis and lysis of tumour cells release lots K+ ions into body

57
Q

What is Wilson’s disease?

A

Excessive copper in tissues

  • autosomal recessive
  • can increase production of free radicals by contact with unbound Cu
58
Q

What is one method to diagnose cell death?

A

Dye exclusion technique:

  • dye into cell medium
  • if it doesn’t enter cell → cell membrane intact and cell is alive
  • if it does enter cell → cell membrane not intact and cell is dead

Better to test for cell death by looking at functional rather than morphological criteria

59
Q

Describe myoglobin leakage

A

Myoglobin is found in striated tissue (heart and skeletal muscle).
When damage occurs to these striated cells it causes the release of myoglobin into the extracellular space.
It can cause a condition know as myoglobinuria as a build up of myoglobin can block the kidneys where it’s excreted and result in renal failure.

60
Q

What is Pathological calcification?

A

Pathological calcification is an abnormal deposition of calcium salts within tissues.

61
Q

What are the 2 types of calcification of tissues?

A
  • dystrophic (localised), more common

- metastatic (generalised)

62
Q

Where does dystrophic calcification occur?

A
  • area of dying tissue
  • atherosclerotic plaques
  • aging or damaged heart valves
  • in tuberculus lymph nodes
  • some malignancies`
63
Q

Why does dystrophic calcification occur?

A
  • No abnormality in calcium metabolism, or serum calcium or phosphate concentrations
  • Local change/disturbance favours nucleation of hydroxyapatite crystals
  • Can cause organ dysfunction, e.g., atherosclerosis, calcified heart valves
64
Q

Why does metastatic calcification occur?

A

•Due to hypercalcaemia secondary to disturbances in calcium metabolism

•Hydroxyapatite crystals are deposited in normal
tissues throughout the body

•Usually asymptomatic but it can be lethal
•Can regress if the cause of hypercalcaemia is
corrected

65
Q

Where does metastatic calcification occur?

A

disturbance is body-wide

66
Q

What causes hypercalcaemia?

A
  • Increased secretion of parathyroid hormone (PTH) resulting in bone resorption
  • Destruction of bone tissue
67
Q

What are the causes of hyperparathyroidism?

A

Primary:
- due to parathyroid hyperplasia or tumour

Secondary:
- due to renal failure and the retention of phosphate

Ectopic:
- secretion of PTH-related protein by malignant tumours (e.g., carcinoma of the lung)

68
Q

What causes destruction of bone tissue?

A

• Primary tumours of bone marrow, e.g., leukaemia,
multiple myeloma
• Diffuse skeletal metastases
• Paget’s disease of bone - when accelerated bone
turnover occurs
• Immobilisation

69
Q

Define oncosis.

A

cell death with swelling, the spectrum of changes that occur prior to death in cells injured by hypoxia and some other agents.

70
Q

Define necrosis.

A

in a living organism the morphologic changes that
occur after a cell has been dead some time, e.g., 4-24 hours.

Note that necrosis describes morphologic changes and is not a type of cell death, i.e., it is an appearance and not a process.

71
Q

Where does coagulative necrosis occur and what is the exception?

A

Usually occurs in ischaemia of solid organs

Exception: brain (liquefactive necrosis).

72
Q

Where does liquefactive necrosis occur?

A

Usually occurs in ischaemia of loose tissue (where there is an absence of stroma), infective aetiologies.

73
Q

What are the 4 types of necrosis?

A

2 main types:

  • coagulative
  • liquefactive (colliquitive)

2 other special types:

  • caseous
  • fat necrosis
74
Q

What is the difference between coagulative and liquefactive necrosis?

A

When cells are dying their proteins can either undergo denaturation (as denatured proteins tend to coagulate this is called coagulative necrosis) or autolysis (where the proteins undergo dissolution by the cells own enzymes = liquifactive necrosis).

coagulative = Protein denaturation
liquefactive =

75
Q

What occurs in coagulative necrosis?

A
  • Denaturation and aggregation of proteins dominates over release of active proteases.
  • Cellular architecture is somewhat preserved, “ghost outline” of cells (collagenous stroma is more resistant to dissolution).

e.g. myocardium necrosis following ischaemia

76
Q

What occurs in liquefactive necrosis?

A
  • Enzyme degradation is substantially greater than denaturation.
  • Leads to enzymatic digestion (liquefaction) of tissues
  • site of necrosis will eventually be marked by a cyst

e.g. brain ischaemia leading to neural necrosis

77
Q

What occurs in caseous necrosis?

A

• Contains amorphous (structureless) debris.
(c.f. ghost outline in coagulative necrosis).

  • Particularly associated with infections e.g. especially tuberculosis.
  • Histological examination shows amorphous eosinophilic area, stippled by haemotoxyphylic nuclear debris.

caseum = cheese

78
Q

What occurs in fat necrosis?

A

Fat necrosis may be due to:
• direct trauma to adipose tissue and extracellular liberation of fat
• enzymatic lysis of fat due to release of lipases

Following trauma to adipose tissue, the intracellular release of fat elicits a brisk inflammatory response, with macrophages phagocytosing the fat, proceeding eventually to fibrosis. The result may be a palpable mass, particularly at a superficial site such as the breasts (not to be misdiagnosed with cancer).

In acute pancreatitis, there is a release of lipase. Fat cells have their stores of fat split into fatty acids, which then combine with calcium and precipitate out as white soaps. In severe cases hypocalcaemia can ensue.

79
Q

What should caseous necrosis raise a suspicion of?

A

Tuberculosis.

80
Q

Define gangrene.

A

Necrosis visible to the naked eye

- An appearance of necrosis

81
Q

Define infarction.

A

Necrosis caused by ischaemia.

  • cause of necrosis
  • can result in gangrene
82
Q

Define infarct.

A

An area of necrotic tissue which is the result of ischaemia

- An area of ischaemic necrosis

83
Q

What is dry gangrene?

A

Necrosis modified by exposure to air
- coagulative necrosis

e.g. umbilical cord necrosis after birth

84
Q

What is wet gangrene?

A

Necrosis modified by infection with a mixed bacterial culture
- liquefactive necrosis

85
Q

What is gas gangrene?

A

Wet gangrene where the infection is with anaerobic bacteria that produce visible and palpable bubbles of gas
- most common is clostridium perfingens

86
Q

Define thrombus.

A

Presence of a blood clot thats been formed abnormally in blood vessel that obstructs blood flow.

87
Q

Define embolus.

A

Any detached intravascular solid, liquid or gaseous material that forms a mass that is carried by the blood to a site that is distant to the site of origin
- can be formed from a thrombus.

88
Q

What can cause tissue infarction?

A
  • thromus
  • embolus
  • compression on blood vessels (due to growth of mass)
  • twists in structures:
    • spermatic cord (testicular torsion)
    • bowel twisted in its own mesentery
89
Q

What is a white (anaemic) infarct?

A

• lack of hemorrhaging
• occlusion of an end artery (i.e., any artery that is
the sole source of arterial blood to a segment of an organ)
• tissues most likely to be affected are solid organs - organs typically include single blood supply
• infarct generally results grossly in a wedge (apex closest to the occlusion)

  • coagulative necrosis
  • Heart, kidneys, spleen
90
Q

What is a red (haemorrhagic) infarct?

A
  • bleeding into the dead tissue
  • mostly commonly because organ/tissue has dual blood supply - brain, lung - blood delivered from other supply but not enough
  • occurs in loose tissue
  • numerous anastomoses
  • Prior congestion
  • Raised venous pressure
  • white infarcts can become red with re-perfusion
91
Q

What does degree of infarct depend on?

A
  • Alternative blood supply
  • Speed of ischaemia
  • Tissue involved (some organs more susceptible, worse in certain organs)
  • Oxygen content of the blood
92
Q

What is ischaemia re-perfusion injury?

A

Paradoxically, if blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than if blood flow hadn’t been returned.

93
Q

What can cause ischaemia re-perfusion injury?

A
  • Increased production of oxygen free radicals with reoxygenation.
  • Increased number of neutrophils resulting in more inflammation and increased tissue injury (oedema, subsequent tissue injury)
  • Delivery of complement proteins and activation of the complement pathway (similar effects to inflammatory response)
94
Q

What do injured and dying cells look like under a light microscope?

A
  • Cytoplasmic changes
  • Nuclear changes
  • Abnormal cellular accumulations
95
Q

Define apoptosis.

A

Cell death with shrinkage, induced by a regulated intracellular program where a cell activates enzymes that degrade it’s own nuclear DNA and proteins.

  • Characteristic microscopic appearance
  • Characteristic DNA breakdown
96
Q

What are some differences between apoptosis and necrosis/oncosis?

A

Apoptosis:

  • no inflammatory response
  • cell membrane integrity maintained
  • active process
  • lysosomal enzymes not involved
  • shrinkage
  • single cells
  • physiological or pathological

Necrosis/oncosis:

  • inflammation
  • cell membrane disrupted
  • passive
  • groups of cells
  • always pathological
97
Q

When does apoptosis occur physiologically?

A
  1. In order to maintain a steady state
  2. Hormone-controlled involution
  3. Embryogenesis (e.g. production of separate fingers from webbed fingers, glands)
98
Q

When does apoptosis occur pathologically?

A
  • Cytotoxic T cell killing of virus-infected or neoplastic cells
  • When cells are damaged, particularly with damaged DNA
  • Graft versus host disease
99
Q

What is graft vs host disease?

A

The donated bone marrow or peripheral blood stem cells view the recipient’s body as foreign, and the donated cells/bone marrow attack the body.

100
Q

What are the 3 phases of apoptosis?

A
  • Initiation
  • Execution
  • Degradation & phagocytosis (of apoptotic bodies)
101
Q

What mechanisms trigger initiation and execution phase of apoptosis, and what do they result in?

A

Triggered by two mechanisms: intrinsic and extrinsic

• Both result in activation of caspases

102
Q

What are caspases?

A
  • Enzymes that control and mediate apoptosis

- Cause cleavage of DNA and proteins of the cytoskeleton

103
Q

What are the triggers for intrinsic pathway of apoptosis?

A

intrinsic pathway of apoptosis?
Initiating signal comes from within the cell

Triggers:

  • Most commonly irreparable DNA damage
  • Withdrawal of growth factors or hormones
104
Q

How does intrinsic pathway of apoptosis lead to activation of caspases?

A

p53 protein is activated and this results in the outer mitochondrial membrane becoming leaky

Cytochrome C is released from the mitochondria and this causes activation of caspases

105
Q

What are the triggers for extrinsic pathway of apoptosis?

A

Initiated by extracellular signals

Triggers:

  • Cells that are a danger,
    e. g., tumour cells, virus infected cells
106
Q

How does extrinsic pathway of apoptosis lead to activation of caspases?

A

• One of the signals is TNFα

  • Secreted by T killer cells
  • Binds to cell membrane receptor (‘death receptor’)
  • Results in activation of caspases
107
Q

What is the end result of apoptosis?

A
  • Both intrinsic and extrinsic pathways cause the cells to shrink and break up into apoptotic bodies
  • The apoptotic bodies express proteins on their surface
  • They can now be recognised by phagocytes or neighbouring cells
  • Finally degradation takes place within the phagocyte/neighbour (preventing damage to the rest of the tissue through inflammation)
108
Q

compare the structural changes in oncosis/necrosis and apoptosis

A

Pattern:
apoptosis = Single cells
oncosis/necrosis = Contiguous groups of cells

Cell size :
apoptosis = Reduced (shrinkage)
oncosis/necrosis = Enlarged (swelling)

Nucleus:
apoptosis = Fragmentation into nucleosome size fragments; form clumps beneath nuclear membrane
oncosis/necrosis = Pyknosis – karyorrhexis -
karyolysis

Plasma membrane :
apoptosis = Intact
oncosis/necrosis = Disrupted, early lysis

Cellular contents:
apoptosis = Intact, released in apoptotic bodies
oncosis/necrosis = Enzymatic digestion, leak out of cell

Adjacent inflammation:
apoptosis = No
oncosis/necrosis = Frequent

109
Q

Compare what happens during apoptosis and necrosis

A

apoptosis:
• shrinkage and chromatin condensation
• cytoplasmic budding
• apoptic bodies phagocytosed with no inflammation as no leakage of cell contents

necrosis:
• swelling
• blebbing with disruption of cell mebrane
• release of proteolytic enzymes with inflammatory reaction

110
Q

describe the microscopic appearances of apoptosis

A

Under the light microscope apoptotic cells are shrunken and appear intensely eosinophilic. Chromatin condensation, pyknosis and karyorrhexis are seen and these take on a distinctive appearance in apoptosis.

Under the electron microscope apoptotic cells show cytoplasmic budding (not blebbing as is seen in oncosis) which progresses to fragmentation into membrane-bound apoptotic bodies which contain cytoplasm, organelles and often nuclear fragments. The apoptotic bodies are eventually removed by macrophage phagocytosis

111
Q

What is replicative senescence?

A

A limitation in the number of times that cells can divide

Ends of chromosomes are called telomeres, with every replication the telomere is shortened. When the telomeres reach a critical length, the cell can no longer divide

112
Q

Which types of cells have the ability to divide more than others and why?

A
  • Germ cells and stem cells contain an enzyme called telomerase - maintains the original length of the telomeres. In this way they can continue to replicate, indefinitely in the case of germ cells
  • Many cancer cells produce telomerase and so have the ability to replicate multiple times

Semester 2 - PathPro (16 decks)

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