2a. Cell Injury

Question 1

What does degree of cell injury depend on?

Answer 1

Type of injury
Severity of injury
Duration of injury
Type of tissue

Question 2

What can cause cell injury?

Answer 2

Hypoxia
Toxins
Physical agents (direct trauma, extremes of temperature)
Radiation
Microorganisms
Immune mechanisms

Question 3

What is the difference between hypoxia and ischaemia?

Answer 3

Ischaemia is insufficient blood flow to provide adequate oxygenation
Hypoxia is reduced oxygen and this can occur when the oxygen content of the arterial blood decreases (anaemia)

Question 4

What are the 4 causes of hypoxia?

Answer 4

Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histiotoxic hypoxia

Question 5

What is hypoxaemic hypoxia?

Answer 5

Arterial content of oxygen is low
Reduced inspired pO2 at altitude
Reduced absorption secondary to lung disease

Question 6

What is anaemic hypoxia?

Answer 6

Decreased ability of haemoglobin to carry oxygen
Anaemia
Carbon monoxide poisoning

Question 7

What is ischaemic hypoxia?

Answer 7

Interruption to blood supply
Blockage of a vessel
Heart failure

Question 8

What is histiotoxic hypoxia?

Answer 8

Inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes
Cyanide poisoning

Question 9

How does the immune system damage the body’s cells?

Answer 9

Hypersensitivity reactions - host tissue injured secondary to overly vigorous immune reaction
Autoimmune reactions - immune system fils to distinguish self from non-self

Question 10

What are the cell components most susceptible to injury?

Answer 10

Cell membranes
Nucleus
Proteins
Mitochondria

Question 11

What happens in the cell in hypoxia (reversible injury)?

Answer 11

Oxidative phosphorylation decreases in mitochondria so less ATP produced
Sodium pump activity decreases so influx of calcium, water and sodium, efflux of potassium (cell swelling, loss of microvilli)
Glycolysis increases, pH and glycogen decreases
Decreased protein synthesis so lipid deposition

Question 12

What happens in prolonged hypoxia to the cell (irreversible)?

Answer 12

Increased cytosolic calcium
Decreased ATP
Decreased phospholipids
Disruption of membrane and cytoskeletal proteins
Nuclear chromatin damage

Question 13

Which of the free radicals are the most dangerous?

Answer 13

OH radical

Question 14

What diseases can free radicals cause?

Answer 14

Haemachromatosis

Wilson’s disease

Question 15

How do free radicals injure cells?

Answer 15

Target lipids in cell membranes
- Cause lipid peroxidation, leads to generation of further free radicals - autocatalytic chain reaction
Oxidise proteins, carbohydrates and DNA
- Molecules become bent out of shape, broken or cross-linked
- Mutagenic therefore carcinogenic

Question 16

How does the body control free radicals?

Answer 16

Anti-oxidant scavengers - donate electrons to free radical (vit A, C, E)
Metal carrier and storage proteins (sequester iron and copper)
Enzymes that neutralise free radicals

Question 17

What names can neutralise free radicals?

Answer 17

Superoxide dismutase
Catalase
Glutathione peroxidase

Question 18

How can the cell protect itself against injury?

Answer 18

Heat shock proteins
Heat shock response aims to mend misfolded proteins and maintain cell viability
Infoldases or chaperonins

Question 19

What can dead cells look like?

Answer 19

Pyknosis - shrinking
Karyorrhexis - breakdown of nucleus
Karyolysis - no nucleus in cell

Question 20

When can abnormal cellular accumulations be seen?

Answer 20

When metabolic processes become deranged

Often occur with sublethal or chronic injury

Question 21

What are the mechanisms of intracellular accumulations?

Answer 21

Abnormal metabolism
Alterations in protein folding and transport
Deficiency of critical enzymes
Inability to degrade phagocytosed particles

Question 22

What can accumulate in cells?

Answer 22

Water and electrolytes
Lipids
Carbohydrates
Proteins
Pigments

Question 23

When does fluid accumulate in cells?

Answer 23

Hydropic swelling
Occurs when energy supplies are cut off
Indicates severe cellular distress
Sodium and water flood into cell

Question 24

When do lipids accumulate in cells?

Answer 24

Steatosis
Often seen in liver
Can be a symptomatic
Causes: alcohol, diabetes mellitus, obesity, toxins

Question 25

How are accumulation of proteins in cells shown?

Answer 25

Seen as eosinophilic droplets or aggregations in cytoplasm

Question 26

What can cause n accumulation of protein in cells?

Answer 26

Alcoholic liver disease | Alpha 1-antitrypsin deficiency

Question 27

What happens in alpha 1-antitrypsin deficiency?

Answer 27

Liver produces incorrectly folded alpha 1-antitrypsin protein Cannot be packaged by ER, accumulates within ER and is not secreted Systemic deficiency - proteases in lung act unchecked resulting in emphysema

Question 28

What causes accumulation of pigment in cells?

Answer 28

Carbon/coal dust/soot Inhaled and phagocytosed by alveolar macrophages Anthracnose and blackened peribronchial lymph nodes Usually harmless unless in large amounts e.g. fibrosis and emphysema

Question 29

What is haemosiderin?

Answer 29

Iron storage molecule Derived from haemoglobin, yellow/brown Forms when there is a systemic or local excess of iron e.g. bruise

Question 30

What is haemosiderosis?

Answer 30

When there is systemic overload of iron, hameosiderin is deposited in many organs Seen in haemolytic anaemias, blood transfusions and hereditary haemochromatosis

Question 31

What is hereditary haemochromatosis?

Answer 31

Results in increased intestinal absorption of dietary iron | Iron is desired in skin, liver, pancreas, heart and endocrine organs - often associated with liver cirrhosis

Question 32

What are the symptoms of hereditary haemochromatosis?

Answer 32

Liver damage Heart dysfunction Multiple endocrine failures

Question 33

What is the treatment of hereditary haemochromatosis?

Answer 33

Repeated bleeding

Question 34

What is jaundice?

Answer 34

Accumulation of bilirubin - bright yellow | Bilirubin deposited in tissues extracellularly or in macrophages

Question 35

What is bilirubin?

Answer 35

Breakdown product of heme, stacks of broken porphyrin rings Formed in all cells of body but must be eliminated in bile Taken from tissues by albumin to liver, conjugated with bilirubin and excreted in bile If bile flow obstructed or overwhelmed, bilirubin in blood rises

Question 36

What happens if molecules leak out of cells?

Answer 36

Can cause local inflammation May have general toxic effects on body May appear in high concentrations in blood and can aid in diagnosis E.g. potassium, enzymes, myoglobin

Question 37

What is pathological calcification?

Answer 37

Abnormal deposition of calcium salts within tissues | Can be localised (dystrophic) or generalised (metastatic)

Question 38

What is dystrophic calcification?

Answer 38

More common than metastatic | Ocurs in area of dying tissue, atherosclerotic plaques, aging or damaged heart valves

Question 39

Hat causes dystrophic calcification?

Answer 39

Local change/disturbance favours nucleation of hydroxyapatite crystals Can cause organ dysfunction

Question 40

What causes metastatic calcification?

Answer 40

Hypercalcaemia secondary to disturbances in calcium metabolism Hydroxyapatite crystals are posited in normal tissues throughout the body Usually asymptomatic but it can be lethal Can regress Increased secretion of PTH resulting in bone reabsorption Destruction of bone tissue