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ESA2 - Mechanisms Of Disease > Cell Injury > Flashcards

Flashcards in Cell Injury Deck (122):
1

What does the degree of cell damage depend on?

- Nature of injury
- Duration of injury
- Severity of injury
- Type of tissue

2

In disease where does the ultimate abnormality lie?

In the cell

3

What are the main causes of cell injury? (7)

- Hypoxia
- Microorganisms
- Physical agents (temperature, trauma)
- Chemical agents (drugs, poisons)
- Autoimmune reactions
- Diet insufficiencies/excess
- Genetic abnormalities

4

What is the difference between hypoxia and ischaemia?

- Hypoxia is OXYGEN DEPRIVATION of tissues and ischaemia is LOSS OF BLOOD SUPPLY to tissues
- Ischaemia can cause hypoxia as lack of blood supply leads to O2 deprivation

5

What are the 4 causes of hypoxia?

- HYPOXAEMIC - arterial content of O2 is low (altitude, lung disease)
- ANAEMIC - decreased carrying capacity of Hb (anaemia, CO)
- ISCHAEMIC - loss of blood supply (heart failure, blockage)
- HISTIOCYTIC - disabled oxidative phosphorylation (CN-)

6

Why can the length of time that a cell can tolerate hypoxia vary?

Different cells have different tolerance levels e.g. NEURONES can only tolerate a few minutes, whereas DERMAL FIBROBLASTS can tolerate hours

7

List 3 physical agents that can cause cell injury

- Extreme temperature
- Direct trauma
- Radiation

8

Describe 2 ways in which immune mechanisms can cause cell injury

- HYPERSENSITIVITY REACTIONS where host tissue is injured secondary to an immune reaction
- AUTOIMMUNE REACTION where immune system fails to distinguish between self and non-self cells

9

List 3 chemical agents that can cause cell injury

- Poisons
- Alcohol/illicit drugs
- Oxygen in high concentrations

10

What cell components are the primary targets for cell injury?

- Plasma membrane
- Nucleus
- Proteins
- Mitochondria

11

Why are proteins considered a primary target for cell injury?

- Proteins have many structural and metabolic roles within the cell
- They form the cytoskeleton and enzymes involved in metabolic processes within the cell

12

When does the cell become fully compromised to cell injury following oxygen deprivation?

- When intracellular ATP concentrations drop to 5-10% of the norm
- ATP is needed for the majority of metabolic processes that occur in cells so decrease in ATP leaves vital processes compromised

13

What is pathology?

The study of disease and cellular malfunction, investigating the structural and functional changes that occur in the cell during disease

14

Define 'oncosis' and explain how this occurs

- Oncosis is CELL DEATH WITH SWELLING
- When intracellular ATP is low, the Na+/K+ pump cannot function
- This results in an influx of Na+ which draws water with it causing the cell and organelles to swell

15

Explain the changes that occur AFTER ONCOSIS of the cell following injury

- Ca2+ enters cell/released from stores in mitochondria and ER
- Activates a number of enzymes (such as phospholipases, endonucleases, proteases and ATPases) which cause damage to cell components
- Digestive enzymes leak out of lysosomes and cause further damage
- Blebbing occurs, followed by cell death

16

When does cell injury become irreversible?

- Decreased ATP production due to O2 deprivation affects the action of the protein channels in the plasma membrane and therefore the integrity
- Loss of membrane integrity (following oncosis) leads to an influx of Ca2+ into the cell which activates potent enzymes that cause irreversible damage

17

Briefly describe how free radicals can cause cell injury

- Cause lipid peroxidation (formation of lipid radicals) which can lead to loss of membrane integrity
- Cause crosslinking and denaturing of proteins
- Cause damage to DNA and increase risk of genetic mutations

18

What defence mechanisms does the body have to protect against free radicals?

- ENZYMES such as superoxide dismutase and catalase
- ANTIOXIDANTS such as glutathione and free radical scavengers (vitamins A, C and E)

19

What are free radicals (ROS)?

Molecules with a SINGLE UNPAIRED ELECTRON that can cause oxidative damage

20

What happens to ribosomes when intracellular ATP levels are low and what is the sequela?

- Ribosomes detach from ER into cytoplasm as ATP is required for them to be attached
- Protein synthesis is compromised which leads to an accumulation of fats and denatured proteins (as enzymatic pathways cannot occur)

21

Define 'necrosis'

The morphological changes that take place after a cell has been dead for some time - changes in appearance occur due to progressive degradation of injured cell by enzymes

22

How could you detect damage to certain cells/tissues using a blood test?

- As cells lose membrane integrity upon injury, intracellular substances leak out into circulation
- Detection of these could indicate damage to specific tissues e.g. Troponin is released by cardiac myocytes upon damage; hepatocytes release transaminases ALT and AST

23

Name a secondary cause of damage to the cell due to lack of oxygen and ATP

- Lack of oxygen activates anaerobic (glycolytic) pathway
- Increased production of LACTATE decreased the intracellular pH which affects the function of many proteins and 'chromatin clumping' occurs

24

What is meant by 'ischaemic-reperfusion injury'?

When blood flow is returned to a tissue that has been subjected to ischaemia but ISN'T NECROTIC, the tissue injury is sometimes worsened that if the blood supply had not been restored

25

Explain 3 ways in which ischaemia-reperfusion can worsen cell injury

- Increased production of ROS SPECIES upon reoxygenation
- Increased number of NEUTROPHILS as blood is reinstated, resulting in more inflammation and increased tissue injury
- Delivery of COMPLEMENT PROTEINS and activation of the complement pathway

26

Give one example of a chemical that can cause cell injury and briefly explain how this occurs

- CYANIDE
- Binds to cellular components (mitochondrial cytochrome oxidase) and inhibits oxidative phosphorylation
- Lack of ATP production begins the pathway of cell damage and death

27

Why could we not live without free radicals?

- Produced by leukocytes and are released to kill bacteria
- Role in cell signalling

28

Name 3 free radicals produced by the body

- Superoxide O2-
- Hydrogen peroxide H2O2
- HYDROXYL OH-

29

Name 2 ways in which dangerous hydroxyl OH- free radicals can be formed

- RADIATION can directly lyse water to form OH-
- FENTON reaction which forms OH- from Fe2+ and H2O2
- HABER-WEISS reaction which forms OH- from superoxide and H2O2

30

What is a heat shock protein? Explain their role and give one example

- HSPs recognise proteins that have been mis-folded or damaged during cell injury and repair them
- They play a key role in MAINTAINING PROTEIN VIABILITY DURING CELL INJURY
- An example of a HSP is Ubiquitin

31

Explain how cytoplasmic changes identified using a light microscope can help to identify injured cells

- Reduced pink staining of cytoplasm due to accumulation of water (reversible)
- Followed by increased pink staining due to detachment and loss of ribosomes from ER and accumulation of denatured proteins (irreversible)

32

Describe the visible nuclear changes that occur during IRREVERSIBLE cell injury

- PYKNOSIS (shrinkage)
- KARRYOHEXIS (fragmentation)
- KARRYOLYSIS (dissolution)

33

Name one reversible nuclear change that occurs following cell injury

CHROMATIN CLUMPING due to reduced intracellular pH

34

List 4 reversible changes that occur during cell injury

- CELL SWELLING due to failure of ionic pumps
- CYTOPLASMIC BLEBS due to cell swelling
- CHROMATIN CLUMPING due to reduced pH
- RIBOSOME SEPARATION FROM ER due to lack of ATP

35

List 4 irreversible changes that occur during cell injury

- Nuclear changes such as pyknosis, karryohexis and karryolysis
- Swelling and rupture of lysosomes
- Membrane defects and lysis of ER
- Amorphous densities in swelled mitochondria

36

When does necrosis occur?

4-24 hrs after cell death (oncosis)

37

What is the difference between coagulative and liquifactive necrosis?

- COAGULATIVE - proteins undergo denaturation and coagulate/clump. Dead tissue is solid
- LIQUIFACTIVE - proteins undergo dissolution by cells own enzymes (proteases). Dead tissue liquifies

38

Describe how coagulative necrosis occurs and state the appearance of the tissue

- DENATURATION OF PROTEINS DOMINATES OVER RELEASE OF ACTIVE PROTEASES
- Dead tissue has a SOLID appearance and is WHITE
- Cell architecture is preserved creating a "GHOST OUTLINE" after a few days
- Appearance is modified following acute inflammatory response and phagocytosis

39

What type of necrosis is commonly seen in tissues with massive neutrophil infiltration (e.g. Abscesses) and why?

- LIQUIFACTIVE
- Neutrophils release PROTEASES so active enzyme degradation is substantially greater than denaturation, leading to enzymatic digestion

40

What tissues are more susceptible to liquifactive necrosis, rather than coagulative and why?

- Tissues such as BRAIN and LUNGS
- Tissues are fragile and have NO SUPPORT from a collagenous matrix
- Dead tissue is a viscous mass and if acute inflammation occurs, PUS is present

41

Describe the appearance of a tissue that has undergone caseous necrosis

- "Cheesy appearance" with amorphous (structure less) debris
- Granulomatous inflammation
- No "ghost outline"

42

Which microbial infection may give rise to caseous necrosis?

TUBERCULOSIS

43

Describe how fat necrosis occurs following acute pancreatitis

- Release of pancreatic LIPASES from damaged pancreatic acinar cells of the inflamed pancreas
- Lipases act on fatty tissue causing fat necrosis and release of free fatty acids
- Fatty acids can calcify forming chalky deposits known as CALCIUM SOAPS or "taches de bougie"

44

Explain how fat necrosis can be mistaken for breast cancer

- Fat necrosis can occur after direct trauma to fatty tissue in breast
- Once healed, it leaves an IRREGULAR SCAR which can mimic a nodule of breast cancer

45

What is gangrene?

- NOT A TYPE OF NECROSIS
- Necrosis that is visible to the naked eye
- Can have DRY or WET gangrene

46

Describe the differences in dry and wet gangrene

- DRY - tissue is left exposed to air and becomes dehydrated so bacteria cannot infiltrate (results from coagulative necrosis)
- WET - tissue is infected by bacterial culture which can infiltrate circulation and cause septicaemia (results from liquifactive necrosis)

47

What is gas gangrene? Give one example of how this may occur

- WET GANGRENE where tissue has become infected by ANAEROBIC BACTERIA which produce palpable bubbles of gas within the tissues
- Occurs during crushing of a limb in a motorcycle accident (injured tissue loses blood supply, becomes necrotic and picks up bacteria from soil)

48

Define 'infarction' in its simplest terms

Necrosis due to ischaemia

49

What is an 'infarct'?

- Area of tissue death (necrosis) caused by obstruction of a tissues blood supply (ischaemia)
- Most infractions are due to thrombosis or embolism

50

List 4 occurrences that can cause an infarct

- THROMBOSIS (blockage of vessel by a thrombus)
- EMBOLISM (blockage by embolus/fragment of thrombus)
- EXTERNAL COMPRESSION of a vessel (by tumour/within hernia)
- TWISTING of vessel (testicular torsion)

51

Give examples of coagulative and liquifactive necrosis caused by ischaemia

- MYOCARDIAL INFARCTION is ischaemic necrosis of the heart and is coagulative
- CEREBRAL INFARCTION is ischaemic necrosis of the brain and is liquifactive

52

Describe the formation of a white infarct and give examples of organs where this may occur

- OCCLUSION OF AN END ARTERY in 'solid' organs, causing ischaemia and coagulative necrosis
- Solid nature of dead tissue limits the amount of haemorrhage
- Tissue appears white due to lack of blood supply
- Occurs in the HEART, SPLEEN and KIDNEYS; appear wedge-shaped with occluded artery at the apex

53

What causes a red infarct to appear red?

Extensive haemorrhage into dead tissue

54

Give 5 examples of where a red infarct may occur

- Organs with a dual blood supply
- Organs with numerous anastomoses
- Loose tissues which do not have a collagenous support (lungs)
- Where venous pressure is increased
- Where there has been previous conjestion

55

Explain how increased venous pressure can lead to a red infarct

- Increased pressure transmitted to capillary bed
- Tissue pressure increases so there is reduced arterial filing pressure, causing ischaemia and necrosis
- Tissue is engorged in blood therefore infarct is red

56

Why do organs with dual blood supplies cause red infarcts?

- Occlusion of the main arterial supply causes an infarct
- Secondary arterial supply is insufficient to rescue the tissue but still allows blood to flow, causing haemorrhage and red infarct

57

What do the consequences of infarcts depend on?

- Whether tissue has a dual blood supply
- How quickly ischaemia occurs (if slow, alternative perfusion can develop)
- How vulnerable tissue is to hypoxia
- Oxygen content of blood (anaemic patients experience more damage)

58

What are the consequences of molecules leaking out of injured cells?

- May have general toxic effects on body
- May cause local irritation or inflammation
- Appear in high concentrations in the blood so can be measured and used to aid diagnosis

59

What is the significance of the release of potassium from an injured cell?

- High concentrations of potassium can cause the heart to stop
- Potassium solution is used to keep the heart still during surgery

60

Explain how high potassium concentrations can reach the heart and cause it to stop

- Myocardial infarction
- Massive necrosis elsewhere in the body (severe burns, tourniquet shock and tumour lysis syndrome)

61

Name 3 principle molecules that are released from cell membranes following damage

- Potassium
- Enzymes (transaminases, troponin)
- Myoglobin

62

How can enzymes in the plasma be used as a useful diagnostic tool in determining cell injury?

- Enzymes that are released into the plasma following cell injury would normally be intracellular and can be detected in blood tests
- Indicates organ involved, timing and evolution of the tissue damage
- e.g. Troponin is released following MI but can only be detected 20mins straight after the occurrence

63

What is the significance of myoglobin release following cell membrane injury?

- Released from dead myocardium or damaged striated muscle, causes rhabdomylosis from burns/trauma, potassium depletion or drug abuse
- Can plug renal tubules and cause renal failure

64

Define 'apoptosis'

- CELL DEATH WITH SHRINKAGE
- Physiological death of a single cell due to activation of regulated intracellular enzymatic reactions

65

What are 'caspases' and what is their cellular function?

- Proteases that are activated and mediate the cellular effects of apoptosis
- Act by breaking up cytoskeleton, cleaving proteins and initiating DNA degradation

66

Explain 3 ways in which apoptosis differs from oncosis/necrosis under a microscope

- In apoptosis the membrane integrity is maintained and there is no leakage or inflammation
- Apoptosis results in cell shrinking, not swelling
- In apoptosis, the chromatin condenses and there is no karyolysis of DNA, budding occurs and formation of apoptotic bodies

67

What is the difference between intrinsic and extrinsic apoptosis?

- INTRINSIC occurs as a result of increased permeability of mitochondrial membrane leading to leakage of proteins and activation of enzymes
- EXTRINSIC occurs due to binding of external ligands to "death receptors" which activate enzymes

68

Describe the process of intrinsic apoptosis and the enzymes involved

- p53 mediates apoptosis in response to DNA damage
- Increased permeability of mitochondria leads to leakage of cytochrome c, which interacts the APAF1 and Caspase9 which form an APOPTOSOME which activates various downstream caspases

69

Describe the process of extrinsic apoptosis

- Receptor mediated by binding of external ligands such as TRAIL and Fas to "death receptors"
- Leads to activation of Caspase8 and other caspases independently of mitochondria

70

What is the role of Bcl-2?

INHIBITS INTRINSIC APOPTOSIS by preventing the release of cytochrome c from the mitochondria

71

Describe the degradation stage of apoptosis

- Budding of cell membrane and contents produces APOPTOTIC BODIES
- These are phagocytosed by neighbouring cells or phagocytes (macrophages)

72

Name 5 abnormal cellular accumulations that can occur following cell injury

- Water and electrolytes
- Lipids
- Proteins
- Carbohydrates
- Pigments

73

What is meant by 'hydroptic swelling'?

- Cell swelling due to osmotic disturbances
- Occurs when ATP production is insufficient for function of ion channels, leading to an influx of Na+ into cell and water follows
- Cells are enlarged but NOT HYPERTROPHIC

74

Explain how cell swelling can cause further problems in certain parts of the body

- In BRAIN cell swelling causes tissue to expand
- No room for expansion due to skull
- COMPRESSION occurs, blood vessels are squeezed and blood supply to brain is reduced

75

What is 'steatosis' and where might this occur in the body?

- Accumulation of TAGs in cells and tissues due to cell injury
- Commonly seen in the LIVER (major organ of fat metabolism) caused by alcohol abuse, DM, obesity and toxins such as carbon tetrachloride

76

How might the liver appear in advanced steatosis?

- Golden yellow in colour
- Enlarged
- When cut, knife is covered in grease

77

What is steatosis a sign of?

ALCOHOLIC LIVER DISEASE

78

Describe 2 ways in which an accumulation of cholesterol can cause visible effects on cell structures

- Accumulation of cholesterol in smooth muscle cells and macrophages of vessels can lead to FOAM CELLS which form atherosclerotic plaques
- Accumulation in skin and tendons during Hyperlipidaemia can cause xanthoma, xanthelasma or corneal arcus

79

How may accumulated proteins appear in damaged cells?

- Eosinophilic droplets
- Aggregates within cytoplasm

80

Explain how α1-antitrypsin deficiency can lead to emphysema of the lungs

- Liver produces incorrectly folded version of α1-antitrypsin that cannot be packaged by ER
- ACCUMULATION within ER and cannot be secreted
- PROTEASES act in lung unchecked which can lead to damage and breakdown of lung tissue

81

Give two examples of exogenous pigments that can accumulate in cells

- CARBON/SOOT in coal-workers pneumoconiosis where coal dust is phagocytosed and leads to BLACKENED LUNGS which can become fibrotic or emphysematous
- TATTOOING where pigments in skin can be phagocytosed by macrophages or enter lymph nodes

82

Give 3 examples of endogenous pigments that can accumulate in cells

- BILIRUBIN (breakdown of Hb in RBC lysis)
- LIPOFUSCIN (from previous lipid peroxidation)
- HAEMOSIDERIN (iron storage molecule derived from Hb)

83

What is the appearance of LIPOFUSCIN in cells?

- YELLOW/BROWN GRAINS in cytoplasm
- Seen in ageing/long lived cells (myocardium) but not in those with a high turnover (epithelia)

84

Give an example of how local overload of iron and haemosiderin can be seen

- HAEMORRHAGE of skin or subcutaneous tissue
- BRUISING

85

What is 'haemosiderosis' and how can this be caused?

- SYSTEMIC OVERLOAD OF IRON into tissues or organs
- Caused by haemolytic anaemia, blood transfusion and hereditary haemochromatosis

86

What are the effects of haemochromatosis and how is this treated?

- Iron deposits (skin, liver, pancreas, heart, endocrine) which can lead to SCARRING, DYSFUNCTION and FAILURE of organs
- Treated by REPEATED BLEEDING

87

What is 'bilirubin' and how can it accumulate?

- Stack of polyphyrin rings that have lost their iron (heme) and is a BRIGHT YELLOW PIGMENT
- If levels rise (due to obstruction or overwhelming of bile flow) this can cause JAUNDICE
- Can be formed anywhere in the body as all cells contain heme in cytochromes

88

Briefly describe the formation and excretion of bilirubin

- Heme groups broken down and iron is lost, forming BILIVERDIN which is harmless
- Biliverdin is broken down into bilirubin which is VERY TOXIC
- Transported from tissues to liver via albumin to be CONJUGATED as excreted in the bile

89

Define 'apoptosis'

- CELL DEATH WITH SHRINKAGE
- Physiological death of a single cell due to activation of regulated intracellular enzymatic reactions

90

What are 'caspases' and what is their cellular function?

- Proteases that are activated and mediate the cellular effects of apoptosis
- Act by breaking up cytoskeleton, cleaving proteins and initiating DNA degradation

91

Explain 3 ways in which apoptosis differs from oncosis/necrosis under a microscope

- In apoptosis the membrane integrity is maintained and there is no leakage or inflammation
- Apoptosis results in cell shrinking, not swelling
- In apoptosis, the chromatin condenses and there is no karyolysis of DNA, budding occurs and formation of apoptotic bodies

92

What is the difference between intrinsic and extrinsic apoptosis?

- INTRINSIC occurs as a result of increased permeability of mitochondrial membrane leading to leakage of proteins and activation of enzymes
- EXTRINSIC occurs due to binding of external ligands to "death receptors" which activate enzymes

93

Describe the process of intrinsic apoptosis and the enzymes involved

- p53 mediates apoptosis in response to DNA damage
- Increased permeability of mitochondria leads to leakage of cytochrome c, which interacts the APAF1 and Caspase9 which form an APOPTOSOME which activates various downstream caspases

94

Describe the process of extrinsic apoptosis

- Receptor mediated by binding of external ligands such as TRAIL and Fas to "death receptors"
- Leads to activation of Caspase8 and other caspases independently of mitochondria

95

What is the role of Bcl-2?

INHIBITS INTRINSIC APOPTOSIS by preventing the release of cytochrome c from the mitochondria

96

Describe the degradation stage of apoptosis

- Budding of cell membrane and contents produces APOPTOTIC BODIES
- These are phagocytosed by neighbouring cells or phagocytes (macrophages)

97

Name 5 abnormal cellular accumulations that can occur following cell injury

- Water and electrolytes
- Lipids
- Proteins
- Carbohydrates
- Pigments

98

What is meant by 'hydroptic swelling'?

- Cell swelling due to osmotic disturbances
- Occurs when ATP production is insufficient for function of ion channels, leading to an influx of Na+ into cell and water follows
- Cells are enlarged but NOT HYPERTROPHIC

99

Explain how cell swelling can cause further problems in certain parts of the body

- In BRAIN cell swelling causes tissue to expand
- No room for expansion due to skull
- COMPRESSION occurs, blood vessels are squeezed and blood supply to brain is reduced

100

What is 'steatosis' and where might this occur in the body?

- Accumulation of TAGs in cells and tissues due to cell injury
- Commonly seen in the LIVER (major organ of fat metabolism) caused by alcohol abuse, DM, obesity and toxins such as carbon tetrachloride

101

How might the liver appear in advanced steatosis?

- Golden yellow in colour
- Enlarged
- When cut, knife is covered in grease

102

What is steatosis a sign of?

ALCOHOLIC LIVER DISEASE

103

Describe 2 ways in which an accumulation of cholesterol can cause visible effects on cell structures

- Accumulation of cholesterol in smooth muscle cells and macrophages of vessels can lead to FOAM CELLS which form atherosclerotic plaques
- Accumulation in skin and tendons during Hyperlipidaemia can cause xanthoma, xanthelasma or corneal arcus

104

How may accumulated proteins appear in damaged cells?

- Eosinophilic droplets
- Aggregates within cytoplasm

105

Explain how α1-antitrypsin deficiency can lead to emphysema of the lungs

- Liver produces incorrectly folded version of α1-antitrypsin that cannot be packaged by ER
- ACCUMULATION within ER and cannot be secreted
- PROTEASES act in lung unchecked which can lead to damage and breakdown of lung tissue

106

Give two examples of exogenous pigments that can accumulate in cells

- CARBON/SOOT in coal-workers pneumoconiosis where coal dust is phagocytosed and leads to BLACKENED LUNGS which can become fibrotic or emphysematous
- TATTOOING where pigments in skin can be phagocytosed by macrophages or enter lymph nodes

107

Give 3 examples of endogenous pigments that can accumulate in cells

- BILIRUBIN (breakdown of Hb in RBC lysis)
- LIPOFUSCIN (from previous lipid peroxidation)
- HAEMOSIDERIN (iron storage molecule derived from Hb)

108

What is the appearance of LIPOFUSCIN in cells?

- YELLOW/BROWN GRAINS in cytoplasm
- Seen in ageing/long lived cells (myocardium) but not in those with a high turnover (epithelia)

109

Give an example of how local overload of iron and haemosiderin can be seen

- HAEMORRHAGE of skin or subcutaneous tissue
- BRUISING

110

What is 'haemosiderosis' and how can this be caused?

- SYSTEMIC OVERLOAD OF IRON into tissues or organs
- Caused by haemolytic anaemia, blood transfusion and hereditary haemochromatosis

111

What are the effects of haemochromatosis and how is this treated?

- Iron deposits (skin, liver, pancreas, heart, endocrine) which can lead to SCARRING, DYSFUNCTION and FAILURE of organs
- Treated by REPEATED BLEEDING

112

What is 'bilirubin' and how can it accumulate?

- Stack of polyphyrin rings that have lost their iron (heme) and is a BRIGHT YELLOW PIGMENT
- If levels rise (due to obstruction or overwhelming of bile flow) this can cause JAUNDICE
- Can be formed anywhere in the body as all cells contain heme in cytochromes

113

Briefly describe the formation and excretion of bilirubin

- Heme groups broken down and iron is lost, forming BILIVERDIN which is harmless
- Biliverdin is broken down into bilirubin which is VERY TOXIC
- Transported from tissues to liver via albumin to be CONJUGATED as excreted in the bile

114

What is 'dystrophic calcification' and where might this occur?

- Local change or disturbance in tissues favours NUCLEATION OF HYDROXYAPATITE CRYSTALS
- No change in calcium metabolism or serum Ca2+/K+ concentration
- Occurs in dying tissue, heart valves (not pulmonary), tuberculous lymph nodes and atherosclerotic plaques

115

How does metastatic calcification differ from dystrophic?

- Metastatic is body-wide whereas dystrophic is localised
- Hydroxyapitate crystals are deposited in normal tissues where there is HYPERCALCAEMIA secondary to disturbances in calcium metabolism

116

Describe 2 ways which hypercalcaemia can occur, leading to metastatic calcification

- Increased secretion of PTH and bone reabsorption by parathyroid tumour, ectopic secretion of PTHrp or renal failure (increased Pi absorption)
- Destruction of bone tissue by bone marrow tumour, diffusion of skeletal metastases, Paget's disease or immobilisation

117

Describe the process of cell ageing

- Accumulations of damage to organelles/DNA, denatured proteins and lipofuscin
- REPLICATION SENESCENCE where telomeres shorten as cells age and replicate (cells lose their ability to divide)

118

Why can some cells (such as stem cells and germ cells) continue to replicate indefinitely?

- Contain TELOMERASE
- Maintains the length of the telomeres so cells can continue to replicate without senescence
- Telomerase is also produced by CANCER CELLS

119

Name 3 effects of chronic excessive alcohol consumption on the liver

- LIVER STEATOSIS (alcohol affects fat metabolism, causing steatosis and hepatomegaly, reversible)
- ACUTE ALCOHOLIC HEPATITIS (toxic metabolites produced from alcohol can cause focal hepatocyte necrosis, reversible)
- CIRRHOSIS (hardening of liver and scarring, irreversible)

120

Explain the pathophysiology of acute alcoholic hepatitis

- Excessive consumption of alcohol leads to build up of toxic metabolites
- Causes ACUTE HEPATITIS with focal necrosis, Mallory body formation and infiltration of neutrophils
- Symptoms include fever, jaundice and liver tenderness. Often reversible

121

Describe one irreversible effect of chronic excessive alcohol consumption on the liver

- CIRRHOSIS
- Appears as hard, shrunken liver with micronodules of regenerating hepatocytes surrounded by bands of collagen
- Damage is irreversible and can be fatal

122

Give examples of pathological and physiological apoptosis

- PATHOLOGICAL - viral hepatitis, toxic injury or tumour
- PHYSIOLOGICAL - embryogenesis and development of limbs (interdigitation)