P2- Injury, Healing and Repair Flashcards

1
Q

Name the causes of cellular / tissue injury.

A
  • Physical - mechanical , thermal ,electric , Barotrauma
  • Chemical - drugs , metabolic , hypoxia , nutrition
  • Infectious - cytolysis , toxins , immune response
  • Immunological -may contribute to other categories
  • Genetic -may contribute to other categories
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2
Q

What can. cause cellular injury?

A

many agents

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3
Q

Describe mechanics by which cell injury manifest , at a cellular level.

A

Mechanisms by which cell injury is manifest may be very similar for different causal agents

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4
Q

what are the different phases of cellular injury?

A
  • reversible

- irreversible

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5
Q

what is cellular injury recognised by?

A
  • morphological / Structural features

- biochemical features

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6
Q

what does severe damage in cellular injury lead to?

A

cell death

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7
Q

What are the vulnerable intracellular systems of mechanics of cellular injury?

A

-Cell Membrane Integrity
-Aerobic Respiration
-Protein Synthesis :
Enzymes
Structural Proteins
-Genomic Integrity

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8
Q

what is closely related in mechanisms of cellular injury?

A

structural and biochemical aspects

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9
Q

what are types of mechanics of cellular injury?

A
  • deficiency of metabolite (o2)
  • impaired metabolism (respiration and syntheis e.g of proteins)
  • Membrane damage (structural -physical/chemical, functional- failure of ion pumps , calcium ion homeostasis )
  • DNA damage or loss (radiation, drugs, free radicals)
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10
Q

describe disruptions to membrane integrity.

A

-Mechanical disruption
Physical trauma, osmotic, freezing, complement, cytotoxic proteins in Tc cells
-Functional disruption
Depletion of ATP, alterations to lipids and protein in the cell membranes e.g. cross linking induced by free radicals
-CSM and internal membranes.

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11
Q

Describe impaired metabolism.

A
Respiration:
-Lack of oxygen e.g blood supply, CO
-Block mitochondrial respiratory chain e.g. cyanide binding to cytochrome oxidase
Protein synthesis;
-Ricin blocks translation at ribosome
-Decreased ATP will contribute
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12
Q

Describe DNA damage / loss.

A

-May not be immediately apparent
-Dividing cells particularly affected – or when there is a growth stimulus
-Non-lethal damage may introduce heritable abnormality that can lead to disease in daughter cells e.g. neoplasia
-Free radicals
Highly reactive and chemically unstable species

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13
Q

Describe metabolite deficiency.

A
Any essential metabolite:
Oxygen:
-Aerobic metabolism
-Anaerobic pathways induce acidosis
-Ischaemia and infarction 
-Reperfusion injury

Glucose

  • Some cells have high requirements and sensitive to deficiency.
  • Diabetes mellitus - poor utilisation - absolute or relative deficiency of insulin

Hormones
-Lack of trophic hormones leads to target cell atrophy

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14
Q

what does the severity of damage and the effects on the cells and tissues depend on?

A
  • Type, magnitude and duration of injury
  • The type of tissue affected
  • The proportion / numbers and types of cells affected
  • The effect on the connective tissue scaffold
  • The effect on other tissues and structures e.g. blood vessels
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15
Q

what are the stages of cellular insult?

A
  • Normal cell
  • cellular insult
  • adaptive response
  • reversible cell injury (loops to adaptive response and normal cell)
  • irreversible cell injury
  • cell death
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16
Q

what occurs in reversible damage?

A
  • Reduced aerobic respiration
  • Increased anaerobic respiration
  • Membrane pumps fail
  • Cell swelling
  • Accumulation of lipids
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17
Q

what is the recognition of cell injury?

A

Cell swelling (Hydropic change) :

  • Cytoplasm pale and swollen
  • Accumulation of fluid
  • Function of membranes and membrane pumps affected
  • Hypoxia and chemical poisons

Fatty change :
-Accumulate lipid droplets
-Uncoupling of lipid and protein metabolism
-Liver commonly affected
-May see many small vacuoles or one large vacuole
(Both of these events are usually reversible )

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18
Q

what is irreversible damage characterised by?

A
  • Severe damage to cell membranes
  • Severe damage to mitochondria
  • Leakage of enzymes
  • Nuclear changes
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19
Q

what happens in irreversible damage?

A

ATP Depletion

Cell Membrane Damage;

  • Progressive Loss of Phospholipids (Increased Degradation, Reduced Synthesis)
  • Lipid Breakdown Products
20
Q

what are the 2 types of cell death?

A

Apoptosis : pre-programmed (decides itself)

Necrosis : pathological cell death

21
Q

Describe features of apoptosis.

A

-Physiological or
Pathological

-Affects scattered cells: Cells shrink , Apoptotic bodies form, No inflammation

Energy dependent:
Stereotyped sequence of events , Biochemical regulation (Inducers /Inhibitors)

22
Q

Describe features of necrosis.

A
  • Always pathological
  • Affects sheets of cells : Cells swell , Dissolution of organelles, Inflammation
  • Not energy dependent
  • Descriptive terms : Coagulative, Colliquitive Caseous , Fibrinoid
23
Q

what is involved in apoptosis?

A
  • inhibitors
  • inducers
  • Molecular mediators and regulators
  • increased apoptosis (AIDS)
  • decreased apoptosis (Neoplasia)
24
Q

what is the outcome of complete repair after injury and damage?

A

Regeneration Restitution

25
Q

what is the outcome of incomplete repair after injury and damage?

A

repair scarring

26
Q

what is the outcome of cell injury affected by?

A

The type of cell affected:

  • Adaptive capability of cell affected
  • Pre-existing disease

The damaging agent:

  • Duration / Severity of exposure
  • Damage that affects structures required for healing eg blood vessels with radiation

Other host factors

27
Q

what are the classifications of cell types?

A
Labile :
GI Tract, Bone Marrow
Stable:
Hepatocytes, Endothelium
Permanent:
Neurones, Skeletal Muscle
28
Q

what are cells that are lost replaced by?

A

a pool known as stem cells

29
Q

where are stem cells located?

A

in discrete compartments

30
Q

what does the integrity of stem cell compartment determine?

A

the regenerative capacity of the tissue

31
Q

what is stem cells vulnerable to?

A

radiation:

  • impair regenerative capacity
  • transmit mutations to daughter cells
32
Q

Describe complete repair.

A

Labile and stable cell populations :

  • Proliferate to replace lost cells
  • Cessation with contact inhibition

Death of permanent cell populations – return to normal is not possible.

Tissue architecture must be preserved
Examples: Hepatitis A

33
Q

what does repair with scarring follow?

A

injury with damage to tissue architecture

34
Q

what does repair with scarring require?

A

formation of granulation tissue

35
Q

How does repair with scarring proceed through?

A

organisation to fibrosis ( scarring)

-fibrous scar contracts by up to 80%

36
Q

what is an important precursor to repair damaged tissue?

A

granulation tissue

37
Q

Describe formation of granulation tissue?

A
  • Capillary endothelial cells proliferate, grow into the damaged area and form fragile vascular channels
  • Admixed with other cells: neutrophils, macrophages and fibroblasts and myofibroblasts
  • Collagen deposition is associated with scar formation that gradually matures and contracts (by up to 80%)
38
Q

What is first intention repair with scarring?

A

Surgical scar

  • closely apposed edges
  • minimal granulation tissue
  • minimal fibrosis
39
Q

What is second intention repair with scarring?

A

Ulcerated surface

  • Edges widely separated
  • prominent granulation tissue
  • prominent fibrosis
40
Q

what is wound contraction caused by?

A

action of myofibroblasts

41
Q

what does wound contraction minimise?

A

volume of wound

42
Q

what is wound contraction a value of?

A

wound contraction

43
Q

when can wound contraction cause problems?

A
  • Stenosis or stricture eg GI tract, CBD

- Contracture may also cause cosmetic damage and impair mobility

44
Q

what local factors influence wound healing?

A
  • Type of cell / tissue
  • Type of injury (comminution, compound)
  • Foreign material (exogenous, interposed soft tissues)
  • Infection
  • Blood supply
  • Nerve supply
  • Local disease eg neoplasia
  • Stability
45
Q

what systemic factors influence wound healing?

A

-Age

-General health:
Nutrition ( General diet,
Vitamin C)
Specific diseases (Diabetes mellitus, Immunodeficiency)
Drugs(Steroids, Cytotoxic drugs )
46
Q

Excessive scar formation.

A
  • Hypertrophic scar

- Keloid