Week 1: Cell death and adaptation Flashcards

1
Q

What is the cellular injury?

A

The non-lethal response to a damaging agent, results in a loss of normal functioning.

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2
Q

What are the potential outcomes of cellular injury?

A

Cellular injury may be short lived hence reversible
Alternativly cell injury can be prolonged, leading to cell death.

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3
Q

What factors affects the amount of function lost as a result of cellular injury?

A

The number of cells, and the extend to which these cells are injured

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4
Q

In what scenarios can tissue injury lead to tissue death?

A
  1. Extensive cellular injury so looses regenerative capacity
  2. Tissue retains regnerative capacity but the ECM has severe damage, so damage is permanent and function reduced
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5
Q

What are some common causes of cellular injury?

A
  1. Lack of factors essential for normal cell function
    - ischemia/hypoxia
    -nutrient deficiency
    -neural stimulation
  2. Physical - trauma, temperature
  3. Chemical - drugs, toxins
  4. Inflammation (may be autoimmune)
    5, Metabolic and genetic disorders - diabetes and obesity
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6
Q

What affects a cells susceptibility to injury?

A

Metabolic rate
Anatomical position

For examples cells most vulnerable to hypoxia tend to have a high oxygen demand and are located far away from the nearest blood vessel

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7
Q

Do all cells in a tissue respond equally at the same time to a given injury?

A

No due to different suspectibility to that injury
Some cells will take longer to be injured or killed by that stimuli

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8
Q

What are the clinical methods of detecting cell injury and death?

A

Presentation of symptoms in the patient, due to decreased tissue/organ function
Blood test may detect leaked intracellular contents when severe membrane damage has occured

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9
Q

What are the pathological ways of detecting cell injury and death?

A

Morphological changes in the tissue
Light microscope changes
Gross changes in surgical speciemens

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10
Q

What is sublethal cell injury?

A

Cell injury that is reversible

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11
Q

What are the common morphological changes in sublethal cell injury?

A

Cell swelling - in all cells
Fatty changes - only is some cell types mainly hepatocytes

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12
Q

What is the mechanism causing cell swelling in cellular injury?

A

shown by all cell types, Na/K+ pump failure,
intracellular Na+ conc increases,
intracellular environment has a higher concentration of solutes, causing inward movement of water by osmosis.
Cell swelling is visible on the light microscope
This causes damage to the membrane and organelles that is only visible under the electron microscope

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13
Q

What is the mechanism causes fatty changes in cellular injury?

A

Causative factors: alcohol, toxins, hypoxia, obseity, malnutrion and altered metabolism in diabetes
Intracellular accumulation of lipid due to deranged metabolism
Results in disruption of aerobic glycolysis and beta oxidation of fats

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14
Q

What is another term used to describe cellular swelling of hepatocytes during cellular injury>

A

Hepatocyte ballooning

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15
Q

How can cellular swelling be identifed?

A

In light microscope - increased cytoplasm size, typically cells appear paler stained and loose characteristic shape
Electron microscope may also detect damage to cell membrane and organelles

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16
Q

How can lipid accumulation in hepatocytes be identified?

A

Liver is often enlarged and yellowed in colour
Fat droplets can be seen in histological images of hepatocytes

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17
Q

What are the two different types of cell death?

A

Apoptosis
Necrosis

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18
Q

What are the key features of apoptosis?

A

Programmed cell death
Is a physiological process - hence is neat and tidy
Requires the activation of specific enzymes often caspases
Normally only occurs in single cells
Maintains tissue function

Results in unwanted cells or cells injured beyond repair.

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19
Q

What are the key features of necrosis?

A

Is pathological
Is uncontrolled breakdown by non specific enzyme activation
hence is messy and typically affects a larger group of cells

Is very common after injury.

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20
Q

What are the two different morphologies of necrosis?

A

Coagulative
Liquifactive

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21
Q

What are the features of coagulative necrosis?

A

Most common morphology of necrosis
Injury thoguht to damage structural proteins and enzymes so blocks breakdown of dead tissue.
Causes slower shrinking of cells.
Tissue architecture can be preserved but in a weak and non-functional way.
Cystoplasm becomes opaque and cell outlines still visible
Commonly caused by ischemic conditions

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22
Q

What are the features of liquifactive necrosis?

A

Less common morphology of necrosis
Causes rapid degradation of cells to liquid mass.
Commonly caused by infections - resulting in rapid recruitment of immune cells causing rapid digestion of tissue so loss of normal structure

23
Q

How does the duration of cellular injury/stress effect how that can be detected?

A

Originally short duration injury is reversible
When injury prolongs to irreversible the original can is at the biochemical levels
Changes then occur to ultrastructure, light microscope detectable then morphological changes visible to the eye.

24
Q

What are the key processes in necrosis of a cell?

A

Severe injury - ischemia, toxins, burn. chemical or physical injury
Results in denaturation of cellular proteins
Leakage of cellular content through damaged membranes, which can then act as DAMPs activating macrophages causing local inflammation.
Enzymatic digestion of the damaged cell, in severe cases lysosomal enzymes may enter the damaged cell cytoplasm through the damaged membrane.

25
Q

What is the process of co-agulative necrosis?

A

Injury damages cell membrane content and proteolytic enzymes - so damaged components not broken down initially.
Leakage of cell content, acts as DAMPs triggering a localised inflammatory response
Immune cells recruited to the area secrete lysosomal enzymes to digest damaged tissue
DAMPs also attract macrophages to phagocytose and clear the damaged tissue
Results in granulation tissue formation

26
Q

What are the key features of a histological slide showing coagulative necrosis?

A

Purple dots showing immune cells
Pink blobs of necrotic tissue

27
Q

What is the gross appearance of coagulative necrosis?

A

Pale tissue with yellow colour from acute inflammatory cells
If blood is flowing into tissue haemorrhage may be present - this is most common is areas of acute inflammation and dual blood supply.

28
Q

What type of necrosis is more common in the brain?

A

Liquifactive

29
Q

How is liquifactive necrosis shown on a histological image?

A

Pale zone of liquid - lack of structure or cellular content

30
Q

What are the outcomes after necrosis?

A

Regeneration from progenitor cells
Scar formation

31
Q

What is dystophic calcification in regard to necrosis?

A

Occurs if necrotic cells are not cleared fast enough.
Calcium ion are deposited, remains present as a form of scar tissue.

32
Q

What are the cellular changes during apoptosis?

A

May be activated by extrinsic or intrinsic pathways.
The cell shrinks and chromatin condenses
Membrane starts blebing
Organelles disintegrate
Nucleus and organelles collapse
Membrane continues to bleb
Apoptotic bodies form
Macrophages phagocytose apoptotic membrane bound bodies form

33
Q

What do apoptotic cells tend to look like under a microscope?

A

Shrunken cells
Smaller and darkly stained nucleus
Or darker small staining round sfragments of nucleus
Apoptotic bodies look like small darker staining round bodies

34
Q

In what physiological scenarios may apoptosis occur?

A

Embryogenesis
Death of neutrophils and lymphocytes at the end of the inflammatory response
Breakdown of hormone dependent tissues, such as breast involution post lactation.

35
Q

What pathological situations can trigger apoptosis?

A

DNA damage (by radiation, hypoxia, cytotixic drugs)
Accumulation of misfolded proteins in the endoplasmic reticulum - may be due to viral infection or genetic mutation
Atrophy of organs where duct obstruction occurs.

36
Q

How can apoptosis be dysregulated?

A

Reduced apoptosis - mutations in genes affecting apoptosis process (p53 MDM2 FASL, FAS etc)
Increases apoptosis - in ishcemic injury where pathway is activated such as in neurodegenerative diseases

37
Q

What is gangrenous necrosis?

A

Clinical term - not a specific pattern of cell death
Normally occurs after coagulative necrosis in multiple layers and a loss of blood supply
results in a massive inflammatory response
Mostly found in limbs and intestines
Extremities mumify
Wet gangrene - when a superimposed infection causes liquifactive necrosis

38
Q

What is fat necrosis?

A

Local areas of fat destruction
Normally from physical damage or chemical damage (such as release of lipases during pancreatitis)
Cell membrane of fat cells are liquified forming large liquid spaces, that will be surrounded by inflammatory cells (macrophages)
Fatty acids accumulate and combine with calcium to form white deposits

39
Q

What is the difference between apoptosis being activated in response to a pathological situation and necrosis occuring?

A

Apoptosis does not result in inflammation
Necrosis does result in inflammation
Necrosis requires damage to the cell membrane initially, apoptosis does not
Apoptosis is typically only one cell
Necrosis is many cells

40
Q

What is the intrinsic pathway of apoptosis?

A

Under normal conditions survival signals, result in production of anti-apoptopic proteins that maintain mitochondrial membrane integrity
Under pathological circumstances, mechanisms are activated so survival signals are lost and pro-apoptopic proteins are produced.
For example p53 detects DNA damage causes upregulation of BAD and BAX.
These increase the permeability of the mitochondrial membrane
Cytochorme C release
Binds to APAF1
Activates CASP9 led caspase cascapde
Eventually CASP3 activated leading to apoptosis

41
Q

What is the extrinsic pathway leading to apoptosis?

A

Activation by activation of plasma mebrame death receptors, members of TNF receptor family.
Most well known FasL bind to Fas receptor on cell membrane.
Adaptor protein FADD is activates, which ten binds to and activates caspase-8 resulting in a capsiase cascade.
Eventually caspase 3 is activated resulting in apoptosis

42
Q

What is meant by adaptation to cell injury?

A

Reversible changes to function and structure of a cell in new physiological or pathological conditions, that later resolve without harmful consequences

43
Q

What is the difference between cellular stress and cellular injury?

A

Stress - has no long lasting harmful consequences (maintains function), results in reversible adaptation
Injury - may be reversible or irrevisible but the cell is unable to adapt having a harmful consequence (loss of function)

44
Q

What are the different adaptations to cellular stress?

A

Hypertrophy - increase in size
Hyperplasia - increase in cell number
Atrophy - decrease in size and metabolic activity
Metaplasia - changing phenotype of the cells.

45
Q

Which cell is apoptosis and necrotic? Why?

A

Apoptosis shows blabbing 4
Necrosis shows damage to the cell membrane 3

46
Q

What does fat necrosis look like?

A

Large accumulation of lipids
Eliminate of adipocyte membrane
Ringed by macrophages

47
Q

What is shown in the image?

A

Hemorragia coagulative necrotic bowel

48
Q

What is hypertrophy?

A

Enlargement of cells - results in increase in the size of the organ.
Contain increased amounts of structural proteins and organelles
Caused by increased functional demand or by growth factor/hormonal stimulation

49
Q

What tissues does hypertrophy normally occur in?

A

Limited capacity to divide
Physiology - uterus during pregnancy
Pathology - heart muscle due to hypertension or increased intracardiac pressure

50
Q

What is hyperplasia?

A

Increase in the number of cells in an organ due to proliferation from differentiated cells or pro-genitor cells
Stimulated by hormones or growth factors

51
Q

What types of tissues typically undergo hyperplasia?

A

Tissue with maintained proliferative capacity.
Physiology - hormonal hyperplasia in endometrium during menstal cycle, regeneration of liver when a lob e has been removed
Pathological - increases estrogenic stimulation leading to endometrial hyperplasia - heavy mesntraul bleeding increase risk of cancer

52
Q

What is atrophy?

A

The reduced size of an organ or tissue caused by reduction in the size and number of cells.
Caused by decreased workload, loss of innervation, diminished blood supply, malnutrition and ageing.
Often accompanied by autophagy
Seen in brain

53
Q

What is metaplasia?

A

Change in one differentiated cell type to another better adapted to the stress, thought to be due to change in differentiation signals to the stem cells.

54
Q

What are some examples of metaplasia as an adaptation to cellular injury?

A

Barrets Oesophagus
Smoking - change from cilitaed columnar epithelium in bronchi to stratified sqaoumous, better against noxious chemicals but lost of mucus secretion and cillary clearance.