NAIMMCQ: Pathology

Outline the five steps involved in general wound healing

Answer:

A. removal of central core
B. formation of granulation tissue
C. extracellular matrix deposition
D. scar formation
E. wound contraction

What is healing of a long bone fracture?

Answer:

1. removeal of necrotic bone and debris by macrophages and osteoclasts
2. angiogenesis and fibroblast proliferation
3. callus formation: pluripotential mesenchymal cells from the soft tissue, periosteium and bone marrow proliferate and differentiate, composed of fibrous tissue, cartilage and bone, fusion of osteogenic layers on either side of the callus
4. remodeling phase: newly formed woven bone is gradually converted to lamellar bone, at about 8 weeks the callus is called a secondary or hard callus and it consists mainly of bone
5. stage of consolidation: endocondrial ossification of the cartilage continues, trabecular bone replaces cartilage, the new bone is continuously remodelled and eventually replaced by compact bone, dead bone removed before healing can be completed, eventually the oritinal line of the bone is restored (takes years)

What is the repair of peripheral nerves?

Answer:

1. schwann cells phagocytose degenerative myelin
2. proximal and distal axons degenerate
3. debris is cleared by macrophages
4. schwnn cells proliferate along the former course of the axon along endoneurium
5. proximal axon generates varies sprouts advancing between schwann cells
6. once regenerated axons meet end organ schwnn cells start myelin production

What is repair of skeletal muscle?

Answer:

skeletal muscle cells ar long multinucleated, permanent cells
myonuclei ar unable to divide
1. macrophages clean up intracelular debris
2. satellite cells, mitosis --> myoblasts --> migrate from marginal site to centre of myobibrils, new myofiber nuclei
3. intact basal lamina: keeps both satellite cells and their myoblast progeny within damaged segment, keeps fibroblasts out, allows entry and exit of macorphages
4. after critical mass of myoblasts have formed they begin to fuse to form myotubular giant cells
5. myotubes sent out numerous cytoplasmic processes of which re-establish contact with the original muscle cell
6. cell membranes fuse to facilitat union of regenerated segment with vable myofibre

What is repair of articular cartilage with injuries that involve subchondral bone?

Answer:

haemorrhage, inflammatory response
defects is filled with fibrovascular tissue
differentiation into chondrocytes starts after about two weeks, production of proteoglycans
fibrocartilage formed after 6-8 weeks

What is repair of articular cartilage with erosions, superficial defects?

Answer:

no haemorrhage or inflammation
no repair, lesions persist for long periods without progressing

What is repair of articular cartilage?

Answer:

specific anatomy: no nerves, blood or lymph
chondrocytes responsible for production, maintenance and turnover of matrix
minimal mitotic activty
chondrocytes unable to migrate

What is second intention healing of cutaneous wound healing?

Answer:

occurs When wound edges are far apart with more extensive loss of cells and tissue
occurs in septic wounds of if FB present
takes longer to heal
epithelializaiton may be delayed
more extensive scar formation

What is the process of epithelialization?

Answer:

process of replacement of superficial epithelial cells of skin and mucous membranes: epithelial cells at the wound edge dissasemble connection with basement membrane and adjacent cells, cells express as new surface receptors, movement of cells over the ECM of wound surface, epithelial cells at edge of the wound proliferate
once cells have filled defect they differentitate
inact basement membranes enhance reepithelialization
concurrent inflammation can impair differentiation
concurrent inflammation can impair differentiation: impairs/delays epithelializaiton, ulceration, continuous attempts to cover wound, metaplasia

What are the processes of cutaneous wound first intention healing?

Answer:

occurs if edges are in close proximity
wound needs to be clean and non-septic
initial healing occurs rapidly
epithelialization occurs within days
maturation occurs over longer period
minimal scar tissue formation
tensile strength similar to adjacent tissue

Briefly describe the pathogenesis of granulation tissue formation in a wound, highlighting the important gross and microscopic features.

Answer: Granulation tissue formation is two major processes: fibroblast migration and proliferation and angiogenesis. Migration of the cells begins along the framework formed by plasma proteins and fibrin. This migration is triggered by growth factors. Angiogenesis begins with proteolysis of the basement membrane and ECM of parental vessel. This is followed by migration of immature endothelial cells into the wound. This proliferation of endothelial cells forms solid endothelial tubes. The lumen of the tubes mature into new capillaries. Then there is the formation of gap junctions and recruitment of pericytes and smooth muscle cells to support the new capillary. Grossly, granulation tissue appears as small nodules on the surface of the wound. They are red, hemorrhagic and bleeds easily. Microscopically, fibroblasts and connective tissue fibres grow parallel to wound surface. The proliferating capillaries are arranged perpendicularly to the fibroblasts and are often evenly spaced

What are the types of edema?

Answer: localized: increased pressure ithin veins or lymphatic obstruction
generalized: generallized congestion, hypoproteinamia or increased Na/water retention

What are the three mechanisms to edema formation?

Answer: Alterations to starling forces
1. increased intravascular hydrostatic pressure (factors increase venous pressure more important more important than those increased arterial pressure)
2. decreased palms oncotic/osmotic pressure (hypoproteinemia)
3. increased capillary permeability (inflammatory, allergic rxns)

What are consequences of hemorrhage?

Answer:

amount of loss and rate of loss: closely linked (25% -> hemorrhagic shock, 25% slowly -> anaemia)
site of loss (small amts at critical sites may be fatal--CNS, pericardial sac)

What is aetiology of haemorrhage?

Answer:

trauma: most common
vascular disease: inflammation, neoplasia, degeneration
disorders of clotting: increased tendency to bleed spontaneously or following minimal trauma (coumarin or bracken poisoning)

What are the different classifications of haemorrhage?

Answer:

petechiae (1-2mm, punctate)
purpura (slightly larger, vasculitis)
ecchymotic (2-3 cm, paint brush)
haematoma (blood clotting in a localized area)
haemo-thorax/pericardium, haemarthrosis (blood filling cavity)
extravasation (large region of haem within tissue)
exsanguination (bled-out)

What is congestion?

Answer:

decreased venous outflow from affected part
it is always pathological
described in relation to its distribution or age

What is role of platelets in inflammation?

Answer:

three types of granules: alpha, dense, and lysosome
anucleate
surveillnace role to detect breaches in endothelial surfaces
adhere to subendothelial collagen at site of vascular damage
activated by thrombin or collagen exposure and adhere to exposed subendothelial collagen
release potent inflammatory mediators
platelet derived growth factor induces fibroblast proliferation

What is role of macrophages?

Answer:

mature monocytes
eliminate injurious agents
phagocytose and cytokine production in acute inflammation
initiate process of tissue repair
process and present Ag
can get tissue destruction if inappropriate prolonged activation in chronic inflammation

What are granules in eosinophils?

Answer:

major basic protein
eosinophilic cationic protein
eosinophilic peroxidases
acid phosphatase, catalase
hydrolytic lysosomal enzymes