Q21

Describe the morphological changes seen in cells with irreversible ischaemia?

  • Mitochondrial swelling: influx of Ca, loss of proteins, enzymes, RNA, through hyperpermeable membranes.
  • Lysosomal injury – leakage of enzymes into cytoplasm. – autodigestion.
  • Cell membrane leakage in both directions, fluid in, eg CK,Trop out..
  • Nuclear changes (pyknosis/karyolysis/karyolexis).

What metabolic changes occur in irreversible ischaemia?

  • Inability to reverse mitochondrial dysfunction causing ATP depletion.
  • Disturbances of cell membrane.
  • Contributing mechanisms:
    • Mitochondrial dysfunction;
    • loss of membrane phospholipids;
    • cytoskeletal abnormalities;
    • reactive oxygen species;
    • lipid breakdown products;
    • loss of intracellular amino aids

Q22

What is apoptosis?
Prompt: Describe features and purpose of apoptosis.

  • Programmed cell death / “ suicide programme”
  • Remove degraded- un needed cells, Stop excess growth, Tightly controlled
  • Activates degradation enzymes, Intact membrane packaging(es), Phagocytosis encouraged = end point
  • Non inflammatory

Pass criteria:

  • Physiological or pathological initiators/ Capsases/ Intrinsic/ extrinsic paths
  • Mitochondrial v death receptor

List some important stimuli for apoptosis?

  • Loss of growth/ stimulating hormones (e.g. GH, nerve growth, loss of sex hormones)
  • Excessive DNA damage (via p53 build up)
  • Unfolded protein build up
  • Developmental atrophy, (embryogenesis)
  • Proliferative tissues- homeostasis – non useful cells/ excess to function- loss of contact inhibition
  • Loss of useful cells after finished purpose (e.g. neutrophils/ lymph  post infl)
  • Cells with harmful characteristics (e.g. autoimmune antigens /xs mutations)
  • Infections (viral leading to cell death)
  • Parenchymal damage after duct obstruction

Pass Criteria:

  • 3 concepts

Q23

What systemic factors affect wound healing?

  • Nutrition
    • protein/ Vit C/ zinc/debilitation
  • Metabolic
    • partic diabetes/ hypermetabolic/ unwell/ sepsis
  • Hormonal
    • steroids effect of other hormone deficiencies/ XS catechols
  • Circulatory status
    • shocked/ hypotensive PVD/ venous ob, lymphatic obstruction
  • Age
  • Drugs

Pass criteria:

  • Need 3 factors  + 3 examples

What local factors impede wound healing?

  • Infection
  • Type/ / size  of wound/not opposed
  • Position- eg vasc/mvt/ pressure
  • Foreign bodies
  • Wound vascularity/ local pressure excess
  • Movement- excess
  • Genetic features
  • Excessive granulation “ proud wounds”
  • Neuropathic wounds

Pass Criteria:

  • Bold PLUS at least 3 local factors

Q24

What cell types are present in chronic inflammation?

  • Macrophages
  • Lymphocytes
  • Plasma cells
  • Eosinophils
  • Mast cells
  • Neutrophils

Pass criteria:

  • Bold PLUS 2 others

What processes mediate the persistent accumulation of macrophages seen in chronic inflammation?

  1. Continued recruitment of monocytes (continued expression of adhesion molecules and chemotactic factors)
  2. Local proliferation of macrophages
  3. Immobilisation of macrophages

Pass Criteria:

  • Bold to pass

 

What products are released by activated macrophages in chronic inflammation?

Products associated with tissue injury:

  • Toxic O2 metabolites; Proteases (elastases, collagenases); Neutrophil chemotactic factors; Coagulation factors; AA metabolites; Nitric oxide

Products associated with fibrosis:

  • Growth factors (PDGF, FGF, TGF); Fibrogenic cytokines; Angiogenesis factors (FGF); “Remodelling” collagenases

Pass criteria:

  • Processes in bold and an example of each
  • Simple list (of 5 or more) passes. Better pass if organised into groups

Q25

Describe the factors that affect wound healing?
Prompt: Outline how they affect the healing process.

  • Local: blood supply, denervation, local infection, FB, haematoma, mechanical stress, necrotic tissue, protection, surgical technique, tissue type
  • Systemic: Age, anaemia, drugs, genetic disorders, hormones, diabetes, malignant disease, malnutrition, obesity, systemic infection, temperature, trauma, hypovolaemia, hypoxia, uraemia, vitamin deficiency (C), trace metal deficiency (Cu, Zn)

Pass criteria:

  • At least 3 local and 3 systemic. Must describe effect to pass

Q26

Describe the 2 different forms of pathological calcification.
Prompt: What is meant by dystrophic calcification / metastatic calcification?

  • Dystrophic calcification
    • normal serum calcium
    • in necrotic or dying tissue
  • Metastatic calcification
    • normal tissue
    • abnormal (raised) calcium

Please give an example(s) of dystrophic calcification, and metastatic calcification.

  • Dystrophic calcification
    • atherosclerosis; calcific aortic stenosis; tuberculous node
  • Metastatic calcification – nephrocalcinosis; pulmonary calcinosis; gastric mucosal

Describe the different principal pathological causes of hypercalcaemia, with some clinical examples.
Prompt: Hyperparathryoidism from increased PTH secretion is one example. Can you give another?

  • Increased PTH secretion + bone resorption – hyperparathyroidism
  • Destruction of bone tissue – skeletal metastases, myeloma, Paget’s
  • Vit-D related disorders – sarcoidosis, hypervitaminosis D
  • Renal failure – secondary hyperparathyroidism + phosphate retention

Pass criteria:

  • 2 out of 4

 


Q27

Describe the 2 different forms of pathological calcification and give an example of each.
Prompt: “What is meant by dystrophic calcification / metastatic calcification”?

  1. Dystrophic calcification
    • Normal serum calcium
    • In necrotic or dying tissue
  2. Metastatic calcification
    • Abnormal (raised) calcium
    • Normal tissue

Give examples of each.
Prompt: What type of abnormal calcification is nephrocalcinosis?

  • Dystrophic calcification:
    • Atherosclerosis
    • Calcific aortic stenosis
    • Tuberculous node.
  • Metastatic calcification
    • Nephrocalcinosis
    • Pulmonary calcinosis
    • Gastric mucosal

Describe the different principal pathological causes of hypercalcaemia, with some clinical examples.
Prompt: Hyperparathryoidism from increased PTH secretion is one example. Can you give another?

  1. Increased PTH secretion + bone resorption – hyperparathyroidism
  2. Destruction of bone tissue – skeletal metastases, myeloma, Paget’s
  3. Vit-D related disorders – sarcoidosis, hypervitaminosis D
  4. Renal failure – secondary hyperparathyroidism + phosphate retention

Pass criteria: 2/4


Q28

Describe the main vascular changes that occur with acute inflammation.

  • Vasodilation & incr blood flow via mediators eg histamine, NO action on vasc smooth muscle
  • Increased permeability
  • Stasis (mins)
  • Accumulation of leukocytes on vasc endothelium

Pass criteria:

  • Bold points PLUS 1 other

What are the major mechanisms for the increased vascular permeability that occurs with inflammation?
Prompt: What mediators affect vascular permeability?

  • Gaps due to endothelial contrac via mediators (immediate transient): histamine (fast), bradykinin, sub P, leukotrienes, cytokines(longer). Venules.
  • Direct injury to vessel: immediate sustained eg burns, lytic bact
  • Delayed prolonged  2-12 hrs burn, radiation, toxins mech unclear
  • Leukocyte-dep injury: venules, pul caps, hours
  • Incr transcytosis: vesicles, vacuoles, incr channels VEGF
  • New vessel formation; new bvs leaky; VEGF, mediators

Pass Criteria:

  • Bold PLUS 2 others

Q29

Describe the clinical features of acute radiation syndrome.
Prompt: How do the clinical features of acute radiation injury change with increasing dose?

  • Features are dose-dependent
    • < 200 rem:  Subclinical: mild N & V, minor neutropenia
    • 200-600 rem:  Haematopoietic:  N & V, neutropenia max. at 2 wks, risk of infection
    • 600-1000 rem:  Gastrointestinal:  N, V and diarrhoea, severe neutropenia, death from shock and infection within 2 weeks
    • > 1000 rem:  CNS: Severe N & V, coma within 3 hours, no lymphocytes, death within 36 hours

Pass criteria:

  • Must describe increasing effect on bone marrow with dose to pass

Describe some of the delayed effects of radiation injury.

  • Carcinogenesis: esp leukaemias and thyroid ca in children
  • Blood vessels: fibrosis, narrowing – leads to organ ischaemia
  • Skin:  radiation dermatitis, impaired healing
  • Heart: pericardial fibrosis leading to constrictive pericarditis.
  • Lungs:  radiation pneumonitis with intraalveolar and institial fibrosis
  • Kidneys and urinary tract:  Peritubular fibrosi, loss of glomeruli, bladder fibrosis
  • GIT:  oesophagits, gastritis, enteritis, colitis, proctitis, fibrosis leading to strictures and obstruction
  • Breast: fibrosis
  • Ovary and testis:  fibrosis and infertility
  • Eyes:  cataracts
  • CNS: transverse myelitis

Pass Criteria:

  • Must get carcinogenesis plus effects on at least 3 other systems

Q30

Describe the effects of acute ionising radiation exposure on tissues.

  • Sublethal doses –> delayed effects: mutations, chromosome aberrations, genetic instability.
  • Larger doses kill proliferating cells –> haem, gut most prone; (clinical use vs proliferating cancer cells.).  Vessel endothelial cell injury causes delayed organ dysfunction.
  • Larger still – overt tissue necrosis.
  • Delayed consequences include fibrosis – scarring when parenchymal cells cant regenerate, when vessels are damaged;
  • Carcinogenesis – skin, leukemia, osteogenic sarcomas, lung ca.; thyroid ca in children

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