What is tissue hypertrophy?

  • Increase in cellular size not number leading to overall organ/tissue size increase
  • Cell size increased by more structural components and increased synthesis of cellular proteins
  • Triggered by increased functional demand or stimulation by hormones or growth factors
  • Can be selective hypertrophy of specific sub-organelles

Pass criteria

  • Bold points

What are examples of hypertrophy?
Prompt: How is it classified?

  • Examples
    • Physiological skeletal muscle enhancement through training or uterus under influence of hormones such as oestrogen
    • Pathological such as cardiomegaly in hypertension and CCF (has an upper limit after which regression occurs -> cell injury -> apoptosis/necrosis)

How is hyperplasia different form hypertrophy?

  • Hyperplasia involves an increase in the number of cells


How do leucocytes get to an area of acute inflammation?

  • Margination of WCC in vessels, rolling and adhesion to endothelium (pavementing) (Selectins)
  • Migration and diapedesis across endothelium (PECAM1, CD31, Integrins)
  • Migration towards chemotactic stimulus in tissue (bacterial products, cytokines, IL8, C5A)

Pass criteria:

  • All bold

What is the role of leukocytes in acute inflammation?

  • Recognition and attachment to materials (opsonins) mediated by receptors
  • Killing of microbes: phagocytosis /engulfment /killing and degradation(H2O2-MPO-Halide)
  • Release of products – Amplify the inflammatory reaction (lysosomal enzymes, reactive oxygen/nitrogen)

Pass criteria:

  • 3 out of 5 bold


What is reperfusion injury?

  • Further cell death in ischaemic tissues following restoration of blood flow

Pass criteria:

  • Bold Points

What are the proposed mechanisms of reperfusion injury?

  • Generation of oxygen free radicals – formed from incomplete reduction of in-coming O2 by damaged mitochondria in affected tissue and action of oxidases (generated from ischaemic cells and leucocytes)
  • Associated inflammation –  cytokines, adhesion molecules generated by hypoxic cells; they recruit neutrophils etc in re-perfused tissue; ensuing inflammation causes additional injury
  • Activation of complement system – IgM Ab deposit in ischaemic tissue; restored blood flow brings complement proteins that bind to Ab and are activated; causing further cell injury and inflammation
  • Mitochondrial permeability transition – via reactive O2 species –  effects mitochondrial function – precludes recovery of ATP / energy  supplies for the cell

Pass Criteria:

  • 2 out of 4


What is metaplasia and give some examples?

  • Reversible change (Among differentiated cells such as epithelial or mesenchymal)
  • Where one cell type is replaced by another by reprogramming of precursor stem cells or undifferentiated mesenchymal cells
  • Examples:
    • Respiratory tract: trachea and bronchi in respiratory tract – due to chronic irritation such as smoking; ciliated columnar to stratified squamous
    • GIT: oesophagus – due to chronic gastric acid reflux; squamous to intestinal-like columnar “Barrett’s oesophagus”

Pass criteria:

  • Bold PLUS 1 out of 2 examples

How may metaplasia progress?
Prompt: What is the potential undesirable outcome of metaplasia?

  • Cells lose normal protective function
  • Persistence of influence that initiated the metaplasia initiates malignant transformation (e.g. squamous cell lung ca; adenocarcinoma oesophagus)

Pass Criteria:

  • Bold to pass


What is hypertrophy?

  • Increase in the size of cells – due to the synthesis of more structural components – resulting in an increase in the size of the organ; caused by increased functional demand or by hormonal stimulation. – pathological or physiological

Pass criteria:

  • Bold to pass


Give examples of physiological and pathological hypertrophy.

  • Physiological
    • Skeletal muscle (gym etc – workload); Uterus in pregnancy (hormonal)
  • Pathological
    • Myocardium (due to hypertension, aortic stenosis – workload); BPH

Pass Criteria:

  • One example of each


Describe the process of skin wound healing by first intention.

  • 24 hours: Scab; Neutrophils; Clot
  • 3 to 7 days: Mitoses; Granulation tissue; Macrophage; Fibroblast; New capillary
  • Weeks: Fibrous union

inflammation 1

  • <24 hours: neutrophils at the margins of the incision,. 24 to 48 hours: epithelial cells move from the wound edges and fuse in the midline beneath the surface scab, producing a continuous but thin epithelial layer that closes the wound.
  • By day 3, neutrophils replaced by macrophages. Granulation tissue progressively invades the incision space. Collagen fibres in the margins of incision. Epithelial cell proliferation thickens the epidermal layer.
  • By day 5, the incisional filled with granulation tissue. Neovascularization is maximal. Collagen bridges the incision. The epidermis recovers its normal thickness.
  • During the second week, continued accumulation of collagen and proliferation of fibroblasts. The leukocytic infiltrate, oedema, and increased vascularity have largely disappeared.
  • By the end of the first month, the scar is made up of a cellular connective tissue devoid of inflammatory infiltrate, covered now by intact epidermis.

Pass criteria:

  • Timeline PLUS
  • Clot
  • Inflammation (neutrophils + macrophages)
  • Granulation
  • Remodelling


What are the morphological and chemical changes associated with early cell injury?

  • Decreased generation of ATP
  • Loss of cell membrane integrity
  • Defects in protein synthesis
  • Cytoskeletal damage
  • DNA damage

Pass criteria:

  • 3 out of 5 to pass

What are the phenomena that characterize irreversible cell injury?

  • The first is the inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury
  • The second is the development of profound disturbances in membranefunction

Pass Criteria:

  • Bold to pass

Can you give an example of a protein that leaks across degraded cell membranes?

  • Cardiac muscle – contains a specific isoform of the enzyme creatine kinase and of the contractile protein troponin.
  • Liver (and specifically bile duct epithelium) – contains a temperature-resistent isoform of the enzyme alkaline phosphatase.
  • Hepatocytes – contain transaminases

Pass Criteria:

  • 1 example to pass


What is the difference between ischaemic and hypoxic injury?

  • Ischaemic involves disruption or reduction in blood supply resulting in reduced oxygen delivery, reduced delivery of substrate and reduced removal of metabolic products
  • Hypoxic involves reduced oxygen delivery only. I hypoxic, anaerobic (glycolytic metabolism can continue as new substrate is being delivered).
  • As a result cellular, hence tissue injury is much more rapid in ischaemic injury

Pass criteria:

  • Candidate to clearly differentiate the 2 processes

Describe the morphologic intracellular changes that occur in ischaemic injury.

  • Reversible; Cell swelling, ultrastructural changes including loss of microvilli and cell surface ‘bleb’ formation. Swelling of ER and mitochondria, Myelin figure formation, and clumping of nuclear chromatin
  • Irreversible; severe mitochondrial swelling, plasma membrane damage, swelling of lysosomes

Pass Criteria:

  • Mention of reversible & irreversible changes with examples from each


What is the complement system?

  • Plasma protein system involved in immunity against microbes. Complement proteins numbered C1-9 are present in plasma in inactive forms

Pass criteria:

  • Bold to pass

Describe the main pathways by which complement activation occurs.

  • Classical pathway: involving an antigen-antibody complex
  • Alternate pathway: triggered by microbial surface molecules (e.g. endotoxin). No antibody involvement.
  • Lectin pathway: plasma mannose-binding lectin binds to carbohydrate on microbe
  • All pathways result in cleavage and activation of C3 (most important and abundant complement component)

Pass Criteria:

  • Bold PLUS way activated

How do activated complement products mediate acute inflammation?

  • Vascular effects: increased permeability; vasodilatation (via C3a, C5a mediated histamine release from mast cells)
  • Leucocyte adhesion, chemotaxis and activation: via C5a
  • Phagocytosis: C3b acts as opsonin on microbe and leads to phagocytosis
  • Cell lysis by the membrane attack complex (MAC) – composed of multiple C9 molecules

Pass criteria:

  • Vascular PLUS 1 other


Describe the sequence of cellular events in acute inflammation.
Prompt: What cells are involved in acute inflammation?
Prompt: How do these cells get from the blood vessels to the inflammatory site?

  • Leucocytes are the major cell type involved. In first 6-24 hours neutrophils, and monocytes/macrophages in  24-48 hours
    • Leucocytes line endothelial wall – margination
  • First stasis of blood flow leading to increased leucocytes along endothelial wall
  • Then leucocyte adhesion to endothelial wall and diapedesis or transmigration across into interstitium – extravasation
    • Adhesion and transmigration and recruitment  are mediated by various mediators such as histamine, PAF cytokines and various attraction molecules – variously called immunoglobulins, integrins, selectins, mucin-like glycoproteins
  • Then leucocytes migrate to site of injury- chemotaxis
    • Chemotaxis and activation is mediated thru various bacterial products, cytokines, chemical factors, Ag-Ab complexes products of necrosis
  • Then leucocyte activation to enable phagocytosis and enzyme release
  • Phagocytosis and release of various enzymes from leucocytes

Pass criteria:

  • Bold to pass

Inflammation 11 to 20    Inflammation 21 to 30

Inflammation 31 to 40    Inflammation 41 to 50

Inflammation 51 to 60