Cell Injury, Degeneration & Death

Question 1

Cell Injury

1. difference between reversible and irreversible cell injury? [2]
2. the threshold between reversible and irreversible depends on which 3 factors? [3]

Answer 1

1. reversible = changes to cell due to environmental stress that return to normal once stimulus is removed whereas irreversible = permanent and results in cell death (usually necrosis)
2. depends on type, duration and severity of the injury

Question 2

Mechanisms (Pathogenesis) of Cell Injury

1. effect on cytoplasm/ribosomes [1]
2. effect on mitochondria [2]
3. effect on cell membrane [2]
4. effect on nucleus [2]
5. cause of oxidative stress and how is it formed pathologically? [4]

Answer 2

1. effect on cytoplasm/ribosomes:
   
   • disrupted enzymes, structural protein synthesis and architecture
2. effect on mitochondria:
   
   • disrupted aerobic respiration/ATP synthesis
3. effect on cell membrane:
   
   • disrupted ion concentrations,
   • esp. increased Ca²⁺ ions
4. effect on nucleus:
   
   • disrupted DNA maintenance
   • DNA damage
5. oxidative stress:
   
   • caused by reactive oxygen species (free radicals) which are normally formed in small amounts as a by-product of respiration
   • formed pathologically by:
     
     • absorption of radiation,
     • toxic chemicals,
     • hypoxia etc.

Question 3

Features of Cell Injury

1. what are they? [5]
2. how does cloudy swelling occur? [2]
3. how does fatty change occur? [2]

Answer 3

Nature of changes are same whether reversible or irreversible but reversible are less severe and include particularly:

1. cloudy swelling
   
   • osmotic disturbance:
     
     • loss of energy-dependent Na pump leads to Na influx and build up of intracellular metabolites
2. cytoplasmic blebs
3. disrupted microvilli
4. swollen mitochondria
5. fatty change
   
   • accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism, especially in liver

Question 4

Necrosis

1. define necrosis [1]
2. define infarction [1]
3. histological features of necrosis? [5]
4. types of necrotic tissue? [4]

Answer 4

1. necrosis = unprogrammed cell death
2. infarction = necrosis caused by loss of blood supply
3. histological changes:
   
   • cell swelling
   • vacuolation
   • disruption of cell membranes and its organelles including mitochondria, lysosomes and ER
   • release of cell contents (cell lysis) including enzymes causes adjacent damage and acute inflammation
   • DNA disruption and hydrolysis
4. types of necrotic tissue:
   
   • coagulative
   • colliquitive
   • caseous
   • fat

Question 5

Coagulative Necrosis

1. describe the tissue consistency [2]
2. describe the 2 types [2]

Answer 5

1. firm with tissue outline retained
2. types:
   
   • haemorrhagic:
     
     • due to blockage of venous drainage
   • gangrenous:
     
     • larger area especially lower leg

Question 6

Colliquative Necrosis

1. describe the tissue consistency [2]
2. examples of conditions in which this type of necrosis occurs? [2]

Answer 6

1. tissue becomes liquid and its structure is lost
2. examples found in:
   
   • infective abscess
   • cerebral infarct

Question 7

Caseous Necrosis

1. describe the tissue consistency? [2]
2. give an example of a condition in which this type of necrosis occurs [2]

Answer 7

1. combination of coagulative and colliquitive, appearing “cheese-like”
2. classical for:
   
   • granulomatous inflammation, especially TB

Question 8

What is the cause of fat necrosis?

Answer 8

due to action of lipases on fatty tissue

Question 9

Describe the functional and inflammatory effects of necrosis [4]

Answer 9

1. Functional:
   
   • depends on the tissue/organ
2. Inflammation:
   
   • release of cell contents activates inflammation and causes damage
     
     • either acute with removal of stimulus and then healing and repair
     • or chronic with persistence of stimulus and chronic inflammation

Question 10

Apoptosis

1. definition? [1]
2. features of apoptosis? [4]
3. causes of physiological apoptosis? [5]
4. causes of pathological apoptosis? [3]
5. describe the morphology of apoptosis [4]
6. what is pyknosis? [1]

Answer 10

1. apoptosis = genetically programmed/activated cell death
2. features:
   
   • requires energy and distinct pathways involved
   • plays an important physiological role, but can occur in pathological situations
   • does not cause inflammation but may be caused by immunological mechanisms
3. causes of physiological apoptosis:
   
   • embryogenesis: deletion of cell populations
   • hormone dependent involution: uterus, breast, ovary
   • cell deletion in proliferating cell populations to maintain constant number of cells: epithelium
   • deletion of inflammatory cells after an inflammatory response
   • deletion of self-reactive lymphocytes in thymus
4. causes of pathological apoptosis:
   
   • viral infection: cytotoxic T-lymphocytes
   • DNA damage
   • hypoxia/ischaemia
5. morphology of apoptosis:
   
   • cell shrinkage
   • chromatin condensation (unlike necrosis): packaging up of nucleus = pyknosis
   • membranes of cell and mitochondria etc. remain intact, unlike necrosis
   • but cytoplasmic blebs form and break off to form apoptotic bodies which are phagocytosed by macrophages

Question 11

Depositions

1. definition? [1]
2. describe the typical composition [2]

Answer 11

1. depositions = abnormal accumulation of substances
2. composition may be of:
   
   • normal endogenous substances, e.g.
     
     • normal products of metabolism, including protein, lipid, and carbohydrate
     • pigments (some deposits are both product & pigment)
   • exogenous (foreign) material, e.g.
     
     • pigments
     • industrial material

Question 12

Amyloid

1. describe the nature of amyloid [4]
2. how does amyloid occur? [3]
3. types of systemic deposition of amyloid [2]

Answer 12

1. nature of amyloid:
   
   • soluble protein fibrils of amyloid are organised (abnormally folded) into specific abnormal, insoluble aggregates
   • on morphology, it resembles fibrosis but without prior inflammation
   • amyloid is a general pattern/appearance which can be produced by multiple different proteins, due to multiple different causes (c.f. cirrhosis)
   • amyloid accumulation may be systemic or localised
2. how amyloid occurs:
   
   • excessive production/accumulation of a normal protein
   • production/accumulation of an abnormal protein
   • tendency of protein to misfold
3. types of systemic amyloid:
   
   • AL amyloid:
     
     • immunoglobulin light chain that is produced in B cell neoplasms (e.g. multiple myeloma)
   • AA amyloid:
     
     • serum amyloid associated protein produced in the liver in prolonged chronic inflammation (e.g. rheumatoid arthritis)

Question 13

Pathological Calcification

1. definition? [1]
2. types of calcification? [2]
3. causes of increased serum calcium? [3]

Answer 13

1. deposition of calcium salts
2. types:
   
   • dystrophic
     
     • deposition in abnormal tissue with normal serum calcium
   • metastatic
     
     • deposition in normal, living tissue with raised serum calcium, often in connective tissue of blood vessels
     • can compromise tissue function
3. causes:
   
   • increased levels of PTH (parathyroid hormone)
     
     • primary = parathyroid gland tumour
     • secondary = kidney disease
   • may be systemic effect with cancer