S1) Cell Injury

Question 1

What are the 4 stages of response to cell injury?

Answer 1

Homeostasis, cellular adaption, cellular injury, cell death

Question 2

Causes of cell injury (5)

Answer 2

• Hypoxia/ ischaemia
• Toxins
• Physical agents eg direct trauma, extremes of temperature, changes in pressure and electric currents
• Radiation
• Micro-organisms

Question 3

Name and describe the 4 types of hypoxia

Answer 3

1) Hypoxaemic hypoxia: arterial content of O2 is low
- Altitude and lung disease malabsorption

2) Anaemic hypoxia: decreased ability of haemoglobin to carry oxygen
- anaemia and CO poising

3) Ischaemic hypoxia: interruption to blood supply

4) Histiocytic hypoxia: inability to utilise oxygen
- Cyanide poisoning

Question 4

Reversible hypoxia: What is the primary effect?

Answer 4

Decrease in oxidative phosphorylation, so decrease in ATP levels

Question 5

What is the effect of decreased ATP levels? (3)

Answer 5

1) NaK ATPase
2) Increase in glycolysis
3) Detachment of ribosomes from RER

Question 6

How does reduction of NaK ATPase activity effect the cell?

Answer 6

Cell swelling

ER swelling

Blebs

Question 7

How does an increase in glycolysis affect the cell?

Answer 7

Lowered pH - chromatin clumps

Lowered glycogen

Question 8

How does the detachment of ribosomes affect the cell?

Answer 8

Decreased protein synthesis, causing lipid deposition

Question 9

What is the primary effect of irreversible hypoxia?

Answer 9

Increase in intracellular calcium (from mitochondria and ER)

Question 10

What is the affect of increased intracellular calcium? (4)

Answer 10

Activation of 4 enzymes

• ATPase (decreased ATP)
• Phospholipase (decreased phospholipids)
• Protease (disruption to membrane and cytoskeletal proteins)
• Endonuclease (nuclear chromatin damage)

Question 11

How does the immune system cause damage to cells? (2)

Answer 11

Hypersensitivity reactions

Autoimmune reactions

Question 12

3 types of free radical

Answer 12

Hydrogen peroxide

Superoxide

Hydroxyl

Question 13

How are free radicals produced? (5)

Answer 13

Oxidative phosphorylation

Inflammation

Radiation

Unbound metals in the body

Drugs and chemicals

Question 14

How are free radicals suppressed? (3)

Answer 14

• Anti-oxidant scavengers - vitamins A, C and E and glutathione
• Metal carrier and storage proteins (transferrin for iron and ceruloplasmin for copper)
• Enzymes which neutralise free radicals
  
  • Catalase converts hydrogen peroxide to water and oxygen
  • Superoxide dismutase turns superoxide to hydrogen peroxide
  • Glutathione peroxidase

Question 15

What do free radicals do in the body? (3)

Answer 15

Oxidative imbalance:

1) Lipid peroxidation - creates even more free radicals by autocatalysis
2) Oxidised proteins, carbs and DNA, changing their conformation
3) Mutagenic and carcinogenic

Question 16

How do cells protect themselves?

Answer 16

Heat shock proteins - these mend misfolded proteins

Unfoldases and chaperonins eg ubiquitin

Question 17

Which 4 sites are most susceptible to injury?

Answer 17

Cell membranes, nucleus, proteins and mitochondria

Question 18

How does the cell look during reversible injury?

Answer 18

Blebs

Clumping of chromatin

Autophagy by lysosomes

ER/ mitochondrial swelling

Dispersion of ribosomes

Question 19

How does the cell look during irreversible injury?

Answer 19

Rupture of lysosomes and autolysis

Myelin figures / defects in cell membrane

Lysis of ER

Nuclear pyknosis (dark) or karyolysis (clear) or karyorrhexis (fragmented)

Question 20

What is oncosis?

Answer 20

Cell death with swelling

Question 21

What is necrosis?

Answer 21

The changes that occur after a cell has been dead for some time

Question 22

What are the 4 types of necrosis?

Answer 22

Coagulative
Liquefactive (colliquitive)
Caseous
Fat necrosis

Question 23

Coagulative necrosis:

Where does it occur?

What does it do?

What does it look like?

Answer 23

Ischaemia of solid organs eg the heart

Denaturation of proteins

White - cell architecture maintained (ghost cells)

Question 24

Liquefactive necrosis:

Where does it occur?

What does it do?

What does it look like?

Answer 24

Ischaemia of loose tissues eg brain

Enzyme activation

Red - cell debris remains - lots of neutrophils

Question 25

Caseous necrosis: Why does it occur? What does it look like?

Answer 25

Infection eg TB Cheese like appearance - structureless debris

Question 26

3 types of gangrene + types of necrosis which accompany them

Answer 26

Dry - modified by exposure to air - coag necrosis Wet - modified by infection - liquefactive Gas - wet gangrene with anaerobic bacteria which produce gas

Question 27

How can infarction be caused?

Answer 27

Thrombosis (clot) Embolism (moving clot) Hernia and twisting of vessels

Question 28

What causes white infarcts?

Answer 28

Occlusion of end arteries

Question 29

Where do red infarcts occur and why are they red?

Answer 29

They occur in loose tissue Red because dual blood supply and raised venous pressure cause reperfusion

Question 30

Why is reperfusion after ischaemia sometimes more harmful? (3)

Answer 30

More oxygen free radicals More neutrophils Complement proteins activate complement pathway

Question 31

How does DNA breakdown in apoptosis differ to oncosis?

Answer 31

Apoptosis - controlled degradation Oncosis - DNA is chopped randomly

Question 32

When does physiological apoptosis occur? (3)

Answer 32

Maintaining a steady state Hormone controlled involution Embryogenesis

Question 33

When does pathological apoptosis occur? (3)

Answer 33

Cytotoxic T cell killing of virus infected/neoplastic cells Damaged cells (especially DNA defects) Treatment of leukaemias

Question 34

Describe intrinsic intiation

Answer 34

Signal comes from within the cell Triggered by 1) Irreparable DNA damage 2) Withdrawal of growth factors or hormones P53 activated - makes outer mitochondrial membrane leaky Cytochrome C released - activates caspases

Question 35

Describe extrinsic initation

Answer 35

Triggered by tumour / virus infected cells TNFa released by cytotoxic cells - binds to cell surface activating caspases

Question 36

Budding or blebbing?

Answer 36

Apoptosis - budding Necrosis - blebbing

Question 37

How does the nucleus differ in apoptosis / necrosis?

Answer 37

Apoptosis - cut into nucleosome sized fragments Necrosis - pkynosis (shrinkage), karyolysis (fading) or karyorrhexis (fragmentation)

Question 38

Name 4 cell accumulations

Answer 38

Water - common with ischaemia Lipids Proteins Pigments

Question 39

What is the name given to accumulation of triglycerides?

Answer 39

Steatosis

Question 40

What causes steatosis?

Answer 40

Alcohol, diabetes, obesity, toxins eg CCl4 Mainly in liver

Question 41

Why is cholesterol accumulation damaging? Where can cholesterol be eliminated from?

Answer 41

Accumulates in smooth muscle and macrophages forming foam cells The liver

Question 42

Where is cholesterol present in people with hereditary hyperlipidaemias and what does this cause?

Answer 42

Macrophages in skin and tendons Causes xanthomas

Question 43

What does alcoholic liver disease cause?

Answer 43

Mallory's hyaline (damaged keratin filaments)

Question 44

What cells remove carbon/soot and what can this cause in large quantities?

Answer 44

Alveolar macrophages Fibrosis and emphysema

Question 45

What is haemosiderin/ when is it formed? What causes haemosiderosis?

Answer 45

An iron storage molecule formed during systemic or local overload of iron eg in a bruise Deposition of haemosiderin into organs

Question 46

What causes hereditary haemochromatosis and what does it cause? How is it treated?

Answer 46

Increased intestinal absorption of iron - deposited into skin, liver, pancreas, heart and endocrine organs - causes liver cirrhosis and pancreatic scarring Repeated bleeding

Question 47

What causes jaundice?

Answer 47

Accumulation of bilirubin

Question 48

How is bilirubin formed? How is it carried to the liver? How is it excreted?

Answer 48

Breakdown product of heme Albumin Bile

Question 49

Where does dystrophic calcification occur?

Answer 49

Areas of dying tissue Tuberculous lymph nodes

Question 50

Causes of hypercalcaemia (2)

Answer 50

- Increased PTH secretion causing bone resorption | - Destruction of bone tissue

Question 51

Describe the three types of increased PTH secretion

Answer 51

Primary - parathyroid hyperplasia / tumour Secondary - renal failure and retention of phosphate Ectopic - secretion of PTH related protein by malignant tumours

Question 52

What causes destruction of bone tissue? (4)

Answer 52

Primary tumours of bone marrow Diffuse skeletal metastasis Paget's disease - accelerated bone turnover Immobilisation

Question 53

What controls replicative senescence?

Answer 53

Length of telomeres

Question 54

How do cells respond to the heat shock response?

Answer 54

Decrease usual protein synthesis Increase synthesis of HSPs

Question 55

Fat necrosis: What occurs? How does it appear? Where does it occur?

Answer 55

Lipase releases fatty acids which complex with calcium to form soaps Soaps appear as white chalky deposits Pancreas, breast and salivary glands

Question 56

Differences between apoptosis and necrosis: Number of cells? Membrane integrity?

Answer 56

Apoptosis - single cells, membrane intact Necrosis - group of cells, membrane lysed early

Question 57

Clinical signs of chronic hepatitis (5)

Answer 57

Raised ALT, AST and LDH Raised bilirubin Decreased albumin Raised PT (prothrombin) Raised ammonia

Question 58

Clinical signs of alcoholic liver disease (3)

Answer 58

Raised bilirubin Raised alkaline phosphatase Raised gamma GT

Question 59

Clinical signs of acute pancreatitis? (4)

Answer 59

Raised serum amylase within 24 hours Raised serum lipase from 72-96 hours Glycosuria Possible hypocalcaemia