MoD Session 1 Flashcards Preview

Semester 2 > MoD Session 1 > Flashcards

Flashcards in MoD Session 1 Deck (154):
0

What can disease be considered as?

Consequence of failed homeostasis w/consequent morphological and functional disturbance

1

What does all disease start with?

Cell injury

2

What are the increasing levels of response mounted by a cell as a stimulus moves from being physiological to harmful?

Homeostasis
Cellular adaptation
Cellular injury
Cell death

3

At what point does cell injury become cell death?

When the injury becomes irreversible

4

What can cause cell injury?

Hypoxia
Toxins
Physical agents
Radiation
Micro-organisms
Immune mechanisms
Dietary insufficiency
Genetic abnormalities

5

What is hypoxaemic hypoxia?

Decrease in arterial oxygen content due to altitude or lung disease

6

What is anaemic hypoxia?

Decreased oxygen carriage by haemoglobin caused by anaemia or carbon monoxide poisoning

7

What is ischaemic hypoxia?

Interrupted blood supply caused by BV blockage or heart failure

8

What is histiocytic hypoxia?

Inability of a cell to use oxygen due to disabled oxidative phosphorylation enzymes caused by cyanide poisoning

9

How does the tolerance of hypoxia vary between neurones and fibroblasts before irreversible injury is caused?

Neurones can tolerate a few minutes
Fibroblasts can tolerate a few hours

10

Give examples of toxins that could cause cellular injury.

Glucose/salt in hypertonic solutions
Oxygen at high concentration
Therapeutic drugs

11

Give examples of physical agents that may cause cellular injury.

Direct trauma
Extreme temperature
Changes in pressure
Electric currents

12

How is urticaria (hives) caused?

Hypersensitivity reaction causes host tissue to be injured secondary to an overly vigorous immune response

13

How does Grave's disease cause cellular injury?

Autoimmune reaction which fails to distinguish b/w self and non-self

14

What shows cellular injury when caused by immune mechanisms?

Redness

15

Give an example of a genetic abnormality which can cause cellular injury.

Inborn errors of metabolism

16

By what mechanisms can cellular injury be caused?

Target:
Cell membranes, especially lysosomes
Nucleus
Proteins (structural cytoskeleton and enzymes)
Mitachondria

17

How can hypoxia cause reversible cell injury?

Ischaemia decreases oxidative phosphorylation --> decreases ATP to 5-10% of normal concentration --> cell reacts

18

Why does lipid deposition occur in reversible cell injury caused by hypoxia?

Ribosomes detach from the ER --> protein synthesis is decreased --> lipid is deposited

19

Why does chromatin clump during reversible cell injury caused by hypoxia?

Increased glycolysis lowers pH which in turn causes chromatin to clump

20

How are blebs formed in reversible cell injury caused by hypoxia?

The sodium/potassium pump is disrupted so cell swells as osmotic ions move in w/water allowing blebs to form

21

Why does cytosolic calcium levels increase in irreversible cell injury caused by hypoxia?

Leaky CSM allows calcium entry
ER and mitochondria also increase calcium levels

22

Which enzymes are affected by the increase in cytosolic calcium in irreversible cell injury caused by hypoxia?

ATPase
Phospholipase
Protease
Endonuclease

23

What effects does the high cytosolic calcium levels acting on enzymes within the cell have in irreversible cell injury caused by hypoxia?

Decreases ATP levels
Decreases phospholipid levels
Disrupts membrane and cytoskeleton proteins
Causes nuclear chromatin damage

24

Is the pathogenesis of cell injury due to all insults the same?

No, it may vary and attack different key structures

25

Which three free radicals are of biological significance?

Hydroxyl
Superoxide
Hydrogen peroxide

26

How does the Fenton reaction form free hydroxyl radicals?

Iron(II) is oxidised to iron(III) whilst hydrogen peroxide becomes an hydroxide ion and hydroxyl free radical

27

How does the Haber-Weiss reaction form hydroxyl free radicals?

An oxide ion, hydrogen ion and hydrogen peroxide react to form oxygen, water and a hydroxyl free radical

28

Which free radical is the most dangerous biologically?

Hydroxyl

29

Why must hydrogen peroxide and oxide ions be rapidly removed by the body?

To prevent formation of more dangerous hydroxyl free radicals

30

Why is the Fenton reaction important in bleeding?

Iron is available so there is an increased risk of hydroxyl free radical formation

31

What insults particularly cause free radical production?

Chemical (paracetamol)
Radiation
Ischaemia-reperfusion
Cellular aging
High oxygen concentration

32

What damage do free radicals cause to cellular structures?

Lipid peroxidation
Bent/broken/cross-linked proteins, carbohydrates and nucleic acids

33

Why are free radicals required by leucocytes?

Killing bacteria
Cellular signalling

34

How are free radicals removed?

Antioxidant system

35

Which enzymes are involved in the antioxidant system?

Superoxide dismutase
Catalases
Peroxidases

36

What are free radical scavengers?

Vitamins A, C, E which can sequester metal ions and prevent Fenton reaction

37

What type of proteins are used in the antioxidant system?

Storage

38

What is ischaemia reperfusion injury?

When bloodflow is returned to damaged but not yet necrotic tissue causing damage worse than if the bloodflow was not restored

39

What mechanisms can cause reperfusion injury?

Increased ROS w/reoxygenation
Increased neutrophils causing more inflammation and tissue injury
Delivery of complement proteins activating the complement pathway

40

What cells are heat shock proteins present in?

All at low concentrations

41

What is the function of heat shock proteins?

Mend mis-folded proteins
Maintain cell vitality

42

What type of proteins are heat shock proteins?

Unfoldases/chaperonins e.g. Ubiquitin

43

How does the cell use heat-shock proteins to maintain cell vitality?

Turns off production of other proteins and increases heat-shock protein synthesis

44

What happens to a mis-folded protein if it cannot be re-folded?

It is destroyed

45

What are the stages of cell injury as seen by light microscopy?

Alive --> injured --> dead-pyknosis --> karyorrhexis --> karyolysis

46

What is pyknosis?

Irreversible cell shrinkage

47

Why does an injured cell become more darker staining as its injury becomes less reversible?

Denatured proteins accumulate

48

When does chromatin clumping remain reversible until?

Pyknosis

49

In reversible cell injury, what cellular changes are seen by electron microscopy?

Cell swelling and blebs
Autophagy by lysosomes
Chromatin clumping
Mitochondrial and ER swelling
Dispersion of ribosomes
Aggregation of intramembranous particles

50

In irreversible cell injury, what cellular changes are seen by electron microscopy?

Rupture of lysosomes and autolysis
Pyknosis of nucleus
Mitochondrial swelling w/large densities formed inside
Lysis of ER
Myelin figures
Defects in CSM

51

What is oncosis?

Cell death w/swelling
Spectrum of changes that occur in injured cells prior to death

52

What is the relationship between ATP and oncosis?

There is none - it is an ATP independent process

53

What cellular changes are seen in oncosis?

Cell and mitochondrial swelling
Plasma membrane rupture

54

What is necrosis?

Morphological changes that occur in a living organism after a cell has been dead for some time

55

Typically what period of time after cell death is necrosis seen?

4-24 hours

56

What is apoptosis?

Cell death w/shrinkage induced by a regulated intracellular programme where the cell activates enzymes that degrade its own nuclear DNA and proteins

57

Is apoptosis and active process?

Yes, it's ATP dependent

58

What cellular changes are seen in apoptosis?

Cell shrinkage
Chromatin condenses
Nuclear fragments
Membrane integrity preserved
Apoptotic bodies

59

What does this describe?

Seen w/damage to cell membranes --> cell contents leak out --> inflammation

Necrosis

60

What is fat necrosis?

Destruction of adipose

61

How are chalky deposits formed in fat necrosis?

Lipases free fatty acids which combine with calcium

62

What can cause fat necrosis?

Pancreatitis
Trauma to adipose

63

What can fat necrosis mimic?

Breast cancer nodule

64

What is caseous necrosis?

Amorphous structureless debris associated with TB

65

What is liquefactive necrosis?

Enzymatic digestion of tissues seen in tissues lacking stroma

66

How is pus formed in colliquitive necrosis?

Increased inflammation and neutrophils

67

What is coagulative necrosis?

Denaturation of proteins causing them to coagulate seen in solid organs

68

Why is a 'ghost outline' seen in coagulative necrosis?

Cellular architecture is somewhat preserved

69

How does coagulative necrosis appear histiologically?

Intense pink staining
Small nuclei

70

How can liquefactive and coagulative processes be rescued when occurring in cells which are still alive?

Rescued by heat shock proteins

71

What is gangrene?

Necrosis that is visible to the naked eye

72

What is the difference between dry and wet gangrene?

Dry: tissue dries before infection can take hold
Wet: bacteria or fungi invade before drying completes

73

How can wet gangrene cause septicaemia?

Microorganisms can easily leak into surrounding capillaries

74

How does gas gangrene lead to the development of palpable pockets of gas in a tissue?

Wet gangrene w/anaerobic bacteria

75

Which type of necrosis is associated with ischaemia?

Coagulative

76

What is an infarct?

Area of ischaemic necrosis

77

What two types of infarct are possible?

White
Red

78

Which two types of necrosis can cause an infarct to form?

Coagulative e.g. MI
Liquefactive e.g. Cerebral infarct

79

What can cause an infarction?

Thrombosis and embolism
Compression/twisting of BV - twisted spermatic cord, hernia, twisted bowel

80

How is a wedge shaped white infarct formed?

Arteral insufficiency so not reperfused due to single blood supply --> occluded artery at apex of wedge of infarct

81

How are red infarcts formed?

Venous insufficiency/reperfused/dual blood supply sufficient to cause haemorrhage but not rescue tissue

82

What features are present in tissue which can form a red infarct?

Numerous anastomoses
Loose tissue w/poor stromal support

83

What reduces arterial filling hence causing ischaemia in red infarction?

Capillaries leak causing venous pressure to increase

84

What do the consequences of infarction depend on?

Alternative blood supply
Speed of ischaemia
Tissue involved
Oxygen content of blood

85

What causes release of molecules by injured and dying cells?

Calcium entering damaged membranes

86

What molecules are leaked by injured and dying cells?

Potassium
Enzymes
Myoglobin

87

What are the affects of molecules released by injured and dying cells?

Local inflammation
General toxic effects on body

88

Why can molecules released by injured and dying cells be used for diagnosis?

They may appear in blood

89

What can cause potassium to explode out of dead cells?

Large MI
Severe burns
Tourniquet removal
Tumour necrosis syndrome

90

What is tumour necrosis syndrome?

Where cancer cells are effectively killed so release lots of potassium

91

Why is potassium used in cardiac surgery?

High levels stop the heart

92

In what order are enzymes released by injured and dying cells?

Smallest molecular weight first w/increasing weight w/increasing pore size

93

Give three examples of enzymes released by injured or dying cells.

Creatine kinase
AST
Troponin

94

How does myoglobin released by injured or dying cells cause brown coloured urine?

Dead myocardium or striated muscle releases myoglobin which plugs renal tubes --> greatly increases myoglobin levels in the urine

95

What is apoptosis characterised by?

Shrinkage
Consistent cleavage of DNA breakdown
Use of ATP
Maintained membrane integrity
Lack of lysosomal emzyme involvement
Rapid completion time

96

What is apoptosis used physiologically for?

Sculpting during embryogenesis
Involution of hormones and cytotoxic killer T cells

97

How can apoptosis be identified pathologically?

Individual cell destruction w/shrunken, intensely pink appearance

98

What is the process seen by a cell undergoing apoptosis?

Normal cell --> condensation --> cell buds --> apoptotic bodies

99

Why is there no inflammation in apoptosis?

Apoptotic bodies are removed by phagocytes therefore there is no release of cellular contents

100

How does extrinsic intimation cause apoptosis?

Stressed cell expresses death receptors --> death ligand TRAIL binds --> activates caspase-8

101

How does intrinsic initiation cause apoptosis?

Stimulated by DNA damage or hormone withdrawal --> p53 stimulates mitochondria which stimulates apoptosome --> activated caspase-9

102

What is the process of degradation and phagocytosis seen in apoptosis?

Loss of microvilli and junctions +/- nuclear changes --> fragmentation creating apoptotic bodies --> apoptotic body expresses surface proteins for recognition by phagocytosis

103

Name 7 important apoptotic molecules.

Death receptors
Death ligands
Caspases
p53
Cytochrome C
APAFI
Bcl-2

104

What are caspases?

Effector molecules of apoptosis

105

What is p53?

'Guardian of the genome' which mediates apoptosis in response to DNA damage

106

What does Bcl-2 do?

Prevents cytochrome C release from mitochondria therefore inhibiting apoptosis

107

What causes abnormal accumulations in a cell?

If the cell cannot metabolise something

108

What can abnormal accumulations in a cell derive from?

Cell's own metabolism
Extracellular space - iron in bleeding
Outer environment - dust

109

Can abnormal accumulations in a cell be reversed?

Yes, if cell metabolism recovers

110

What four mechanisms can cause abnormal accumulations in a cell?

Abnormal metabolism
Alterations in protein folding and transport
Enzyme deficiency
Inability to degrade phagocytosed particles

111

How does abnormal accumulation of water and electrolytes cause tissues to become heavy?

Vacuoles/hydropic swelling increase water content

112

What very difficult to treat condition caused by water and electrolyte retention stops breathing?

Cerebral oedema

113

What causes steatosis?

Alcohol
Diabetes mellitus
Obesity
Toxins

114

How are xanthomas formed?

Cholesterol vesicle filled cells form foam cells as cholesterol is not broken down by the body so is stored in membrane bound droplets

115

What forms myelin figures?

Phospholipids

116

What is the first stage of liver disease?

Steatosis

117

How does mild steatosis compare to advanced steatosis?

Mild = asymptomatic
Advanced = increased weight and size of liver

118

What causes abnormal accumulations of carbohydrates?

Secondary to inborn errors of metabolism

119

How are abnormal accumulations of protein seen in cells?

Eosinophilia droplets in cytoplasm

120

What is Mallory's hyaline?

Damaged hepatocyte protein due to accumulation of keratin in alcoholic liver disease

121

How does incorrectly folded alpha 1-antitrypsin lead to emphysema and hepatitis?

Causes alpha 1-antitrypsin deficiency --> accumulates in ER

122

How do exogenous pigments remain in the skin?

Macrophages pick up pigment and stay indefinitely, replaced when they die and remain stained

123

Why is some exogenous pigment found in lymph nodes?

Some is taken up by lymph fluid and taken to nodes

124

Give three examples of endogenous pigments found in the body.

Bilirubin
Heamosiderin
Lipfuscin

125

How is heam converted to a toxic endogenous pigment?

Haem --> biliverdin (non-toxic) --> bilirubin (toxic)

126

What is the irreversible step in bilirubin production from biliverdin?

Breaking of porphyrin ring

127

Why is bilirubin associated with liver disease when it can be formed by all tissues of the body?

It is transported w/albumin to the liver

128

What is heamosiderin?

Iron storage molecule seen in systemic/local excess of iron

129

What causes haemosiderin deposition in tissues?

Bruising

130

What is hereditary haemochromatosis?

Absorption of too much iron which affects the liver and pancreas

131

What is another name for hereditary haemochromatosis?

Bronze diabetes

132

When is lipofuscin seen?

In age/wear and tear in tissues which have been damaged by free radicals

133

What type of cells is lipofuscin not seen in?

Rapid turnover cells

134

What are the three stages of excessive alcohol intake?

Steatosis - reversible
Acute alcohol hepatitis - reversible
Cirrhosis - irreversible

135

What are the S/S of acute alcoholic hepatitis?

Fever
Liver tenderness

136

How does the liver appear in cirrhosis?

Hard and nodular w/scar tissue and macrophages

137

What is dystrophic calcification?

Pathological local deposition of calcium seen in tuberculous lymph nodes and atheroma

138

Is there abnormal serum calcium or calcium metabolism in dystrophic calcification?

Nope

139

What is favoured in dystrophic calcification?

Hydroxyapatite crystal formation

140

Which is the commonest type of pathological calcification?

Dystrophic

141

What is metastatic calcification?

Hypercalcaemia leading to deposition of hydroxyapatite crystals in all tissues

142

What can cause metastatic calcification?

High PTH
Destruction of bone due to tumour
Paget's disease
Immobilisation causing lack of bone formation stimulus

143

What causes cellular aging?

Shortening of telomeres

144

What occurs at a critical telomere length?

Replicating senescence

145

Why can germ cells and stem cells replicate indefinitely?

They contain telomerase which replicates their telomeres

146

How does the pattern of oncosis/necrosis compare to apoptosis?

Oncosis/necrosis: contiguous group of cells
Apoptosis: single cells

147

How does the cell size in oncosis/necrosis compare to that in apoptosis?

Oncosis/necrosis: enlarged (swelling)
Apoptosis: reduced (shrinkage)

148

How does the nucleus of a cell undergoing oncosis/necrosis compare to that of one undergoing apoptosis?

Oncosis/necrosis: pyknosis-karyorrhexis-karyolysis
Apoptosis: fragmentation into nucleosome size fragments

149

How does the plasma membrane compare in oncosis/necrosis to apoptosis?

Oncosis/necrosis: disrupted, early lysis
Apoptosis: intact but w/altered structure, especially orientation of lipids

150

How do the cellular contents compare in oncosis/necrosis and apoptosis?

Oncosis/necrosis: enzymatic digestion which may leak out of cell
Apoptosis: remain intact but may be released by apoptotic bodies

151

Compare adjacent inflammation in oncosis/necrosis to apoptosis.

Oncosis/necrosis: frequent
Apoptosis: does not take place

152

Does oncosis/necrosis have a physiological or pathological role?

Invariably pathological

153

When is apoptosis physiological and when is it pathological?

Physiological to eliminate unwanted cells
Pathological after some forms of cell damage, especially DNA damage