Describe the steps involved in angiogenesis.

  1. Proteolysis of basement membrane of parent vessel – allows formation of capillary sprout and subsequent cell migration
  2. Migration and chemotaxis of endothelial cells – towards angiogenic stimulus
  3. Proliferation of endothelial cells
  4. Lumen formation, maturation, inhibition of growth/remodelling – of endothelial cells, remodelling into capillary tubes
  5. Increased permeability through gaps and transcytosis – recruitment of periendothelial cells to support endothelial tubes, providing maintenance and accessory cell function

Pass: 2


What is steatosis?

Abnormal accumulations of triglycerides within parenchymal cells

Which organs are commonly involved in steatosis?


Heart, muscle, kidneys

Pass: 2

What are the causes of hepatic steatosis?

Alcohol abuse

Toxins (CCl4), protein malnutrition, diabetes mellitus, obesity, anoxia, starvation

In the liver it results from defects in any one of the events in the sequence from fatty acid entry to lipoprotein exit (FFA-esterified to triglycerides- converted into cholesterol and phospholipids or oxidized to ketone bodies- associated with apoproteins to form lipoproteins and released into the circulation)

Pass: 2


Describe the process of fracture healing.

  1. Haematoma formation / fibrin mesh
  2. Ingrowth of inflammatory cells
  3. Activation of osteoprogenitor cells
  4. Woven bone
  5. Callus
  6. Remodelling

Pass: 5 of 6

What factors may interfere with this process?

  1. Displaced / Comminuted
  2. Foreign Bodies
  3. Inadequate immobilisation
  4. Infection
  5. Nutrition Calcium / Phosphate
  6. Diabetes / Systemic Illness

Pass: 5 of 6


What are the three major components of acute inflammation?

  1. Dilation of small vessels leading to increase blood flow.
  2. Increased permeability of the microvasculature enabling plasma protein and leucocytes to leave the circulation
  3. Emigration of leucocytes from the microcirculation to the site of injury

Pass Criteria:

  • Bold to pass
  • Neutrophils predominate in the early inflammatory (6-24 hours) infiltrate and are later replaced by monocytes and macrophages (24-48 hours)

How are leucocytes delivered to the site of injury?

PROMPT – What are the three processes that leucocytes undergo to move from the blood to the site of injury?

  • Multi-step process mediated and controlled by adhesion molecules and chemokines
    1. Margination: Occurs when leucocytes adopt peripheral position along the epithelium. Rolling (transient adherence mediated by selectins), activation and firm attachment (mediated by integrins) to the endothelium.
    2. Transmigration (diapedesis): across the endothelium. Migration through interendothelial spaces typically in post capillary venules.
    3. Chemotaxis: Leucocytes move toward the site of the injury along a chemical gradient of chemoattractants, which can be exogenous or endogenous.

Pass Criteria:

  • Bold to pass

Name some of the chemoattractants responsible for chemotaxis.

  • Most common exogenous agent – Bacterial products
  • Endogenous
    • IL-8
    • C5a
    • Leukotriene B4
    • All bind to specific receptors and promote polymerisation of actin

Pass Criteria:

  • Bold + 1
  • Note – Polymerisation of actin at the leading edge of the cell establishes a “front wheel” drive in the direction of the injury

What chemical mediators are responsible for pain, fever and tissue damage?

  • IL-1
  • TNF
  • Prostaglandins
  • Bradykinin
  • Neutrophil and Macrophage Lysosomal enzymes
  • Oxygen metabolites
  • NO

Pass Criteria:

  • Bold + 1


What are the causes of pancreatitis?

  • Gallstones
  • Alcohol
  • Iatrogenic
  • Viral
  • Hyperlipoproteinaemia
  • Hypercalcaemia
  • Drugs
  • Trauma
  • Shock
  • Vasculitis
  • Genetic mutations
  • Scorpion bite
  • Atheroembolism
  • Duct obstruction (tumour, parasites etc)

Pass Criteria:

  • Bold + 1

What is the likely pathogenesis of acute pancreatitis?

  • Autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes e.g. trypsinogen
  • Causes interstitial inflammation and oedema, proteolysis, fat necrosis and haemorrhage

Pass Criteria:

  • Bold to pass

What are the acute complications of severe pancreatitis?

  • Haemolysis
  • Disseminated Intravascular Coagulation
  • Fluid Sequestration
  • Acute respiratory distress syndrome
  • Diffuse fat necrosis
  • Peripheral vascular collapse
  • Shock
  • Acute renal tubular necrosis

Pass Criteria:

  • 3 answers to pass


What are the characteristics of chronic inflammation?

  • Inflammation for a prolonged period (week or more)
  • Characterised by macrophages, lymphocytes and plasma cells
  • With simultaneous – active inflammation/tissue destruction and attempts at repair by connective tissue, fibrosis

Pass Criteria:

  • 3 of 4 bold to pass

Why does macrophage accumulation persist in chronic inflammation?

  • Continued recruitment of monocytes (continued expression of adhesion molecules and chemotactic factors)
  • Local proliferation of macrophages
  • Immobilisation of macrophages

Pass Criteria:

  • Bold to pass

What are the causes of chronic inflammation?

PROMPT – Can you give an example of each?

  • Persistent infection
    • Tuberculosis
    • Syphilis
  • Autoimmune
    • Rheumatoid Arthritis
    • Multiple Sclerosis
    • Inflammatory Bowel Disease
    • Systemic Lupus Erythematosus
  • Prolonged exposure to an agent
    • Exogenous – silica -> silicosis, foreign body, persistent trauma
    • Endogenous – lipid -> atherosclerosis

Pass Criteria:

  • 2/3 bold with examples


What is Shock?

  • State where reduced cardiac output or effective blood volume results in impaired tissue perfusion and cellular hypoxia

Pass Criteria:

  • Bold concepts

How do microbes initiate septic shock?

PROMPT – What are the mechanisms?

  1. Interaction with innate cells of immune system – example neutrophils, macrophages, monocytes
  2. Interaction with humoral cells of immune system to activate complement and coagulation pathways
  3. Direct action on endothelium (complex, not fully understood) Toll-like receptors recognise microbial elements, and other mechanisms
  4. End result is mediator release examples TNF, IL-6, 8, 10, PAF PAI-1, HMGB1

Pass Criteria:

  • 2 of 3 plus examples of each (at least 1) + understand role of mediators

When DIC develops, what is the process?

  • Induction of procoagulant state by
    1. Increased TF production
    2. Decreased production of Protein C
    3. TF pathway inhibitor Thrombomodulin
    4. Decreased fibrinolysis by increasing plasminogen activator inhibitor
  • Combined with stasis (decreased washout of activated coagulation factors) results in activation of thrombin and fibrin rich thrombi

Pass Criteria:

  • 2 of 4 & understanding of process

What factors determine the severity and outcome of septic shock in an individual?

  • Extent and virulence of infection
  • Immune status of host
  • Presence of other co-morbid conditions
  • Pattern and level of mediator production


What stimuli cause production of inflammatory mediators?

  • Substances released from
    • Necrotic cells
    • Microbial products
    • Cell injury
    • Mechanical irritation

Pass Criteria:

  • 2 to pass

What are the chemical mediators of acute inflammation and what are their actions?

PROMPT – What are the mechanisms?

  • Histamine: vasodilation, increased vascular permeability, endothelial activation
  • Prostaglandins: vasodilation, increased vascular permeability
  • Leukotrienes: increased vascular permeability, chemotaxis, white cell adhesion and activation
  • Platelet-activating factor: vasodilation, increased vascular permeability, chemotaxis, white cell adhesion, degranulation
  • Complement: white cell chemotaxis and activation, vasodilation
  • Cytokines (TNF, IL-1): endothelial activation (adhesion), fever, pain, hypotension, decreased vascular resistance
  • Chemokines: chemotaxis, white cell activation
  • Kinins: increased vascular permeability, vasodilation, pain, smooth muscle contraction

Pass Criteria:

  • 4 to pass including names and actions


Describe the phases of cutaneous wound healing.

  • Inflammation, proliferation and maturation
  • Phases overlap, and separation arbitrary
  • Initial injury -> platelet adhesion and aggregation + formation of clot on wound surface -> inflammation.
  • Proliferative phase -> formation of granulation tissue, proliferation and migration of connective tissue cells, and re-epithelialisation of the wound surface.
  • Maturation involves ECM deposition, tissue remodelling + wound contraction.

Pass Criteria:

  • 2 of 3 phases in bold with correct descriptions to pass

What factors influence cutaneous wound healing?

  • Systemic factors
    • Nutrition: protein deficiency and vitamin deficiency -> retard healing
    • Metabolic status: Diabetes mellitus -> delayed healing
    • Circulatory status: inadequate blood supply or drainage (arteriosclerosis or varicose veins)
    • Hormones e.g. glucocorticoids influence various components of inflammation, also inhibit collagen synthesis
  • Local factors
    • Infection single most important cause of delay in healing
    • Mechanical factors: early motion of wounds
    • Foreign bodies impede healing
    • Size, location and type of wound (mechanism of injury).

Pass Criteria:

  • 2 systemic and 2 local factors to pass

What is wound contraction?

  • Wound contraction generally occurs in large surface wounds.
  • The contraction helps to close the wound by decreasing the gap between its dermal edges + reducing the wound surface area.
  • Important feature in healing by secondary union.
  • Initial steps of wound contraction involve formation, at the edge of the wound, of a network of myofibroblasts.

Pass Criteria:

  • Bold to pass


What is the sequence of events for tissue healing by scar formation?

  1. Blood clot
    • Stop bleeding
    • Create scaffold
  2. Granulation tissue
    • Angiogenesis
    • Migration & proliferation of fibroblasts
  3. Cell proliferation and collagen deposition
    • Extracellular matrix (ECM) deposition
  4. Scar formation
    • Blanching
    • Increased collagen: type 3 then type 1
  5. Wound contraction
    • Myofibroblasts
  6. Connective tissue remodelling
    • ECM synthesis and degradation
  7. Recovery of tensile strength

Pass Criteria:

  • 5 of 7 to pass

How do skin wounds recover tensile strength?

  • Increase in collagen synthesis (type 1) & reduction in collagen degradation (first 2/12)
  • Then structural modification of collagen with cross linking & increased fibre size

Pass Criteria:

  • Bold to pass

What is the approximate time frame for recovery of tensile strength in skin wounds?
Prompt: What is the strength of skin wounds when sutures are removed?

  • Skin wound has 10% tensile strength at 1/52
  • Continues to improve over next 3 weeks
  • Plateaus at ~3/12 when tensile strength is 70-80%
  • May never recover to 100%

Pass Criteria:

  • Concept that very weak at time of suture removal and months to attain plateau phase

Inflammation 1 to 10    Inflammation 11 to 20

Inflammation 21 to 30    Inflammation 31 to 40

Inflammation 41 to 50