Flashcards in Autopsies And Chronic Inflammation Deck (36):
What are the 3 kinds of autopsy?
Coroners- performed on behalf of HM coroner, no consent needed. Performed when patient not seen within 14 days of death by doctor, doctor unable to say what killed them, suspicious death, patient was in care of state or incarcerated
Hospital autopsies- consent is needed from next of kin. May be limited.
What is involved in an autopsy?
Histology, toxicology, biochemistry, microbiology, genetics
What cells are involved in chronic inflammation?
What are the 3 types of giant cell and when are they seen? What do they each look like?
Langhans- TB- nuclei are arranged around periphery
Foreign body- foreign material- nuclei arranged randomly.
Touton- seen in fat necrosis and xanthomas. Nuclei arranged in horseshoe shape
When does chronic inflammation arise?
After or alongside acute inflammation
Chronic persistent infections
Prolonged exposure to toxic agents
What are the possible complications of chronic inflammation?
Excessive fibrosis- fibroblasts are stimulated by cytokines to produce excess collagen. This is normally helpful to wall of infection. If inappropriate can replace normal parenchyma and impair function of organ eg fibrosis of lung of liver cirrhosis.
What can cause cirrhosis?
Alcoholism, chronic hepatitis B or C
What can cirrhosis of the liver lead to?
What is a granuloma?
A lesion that surrounds an agent which the immune system cannot destroy. They have macrophages and lymphocytes at their centre to help destroy the particle and epithelioid histiocytes around the outside to wall of the infection from healthy tissue
What are labile, stable and permanent tissues?
Labile- constantly dividing
Stable- divide when needed
Permanent- cannot divide
What are unipotent stem cells? Give an example
They can only differentiate into one thing eg megakaryocytes
What are multipotent stem cells? Give an example
They can differentiate into a range of things. Eg haematopoietic stem cell
What are totipotent stem cells? Give an example
Can differentiate into any type of cell. Eg embryonic stem cells.
What is the difference between resolution/ regeneration and fibrous repair?
In the first there is an intact tissue scaffold so the tissue can regenerate to how it was before. In the latter this scaffold is gone so the place will be replaced by scar tissue.
Outline the process of fibrous repair
Phagocytosis of necrotic tissue
Proliferation of endothelial cells
Proliferation of fibroblasts and myofibroblasts
Granulation tissue matures into fibrous scar
Scar matures and shrinks
How is collagen made?
Synthesis of tropo collagen- association of triple helix- Gly X Y.
Glycosylation, hydroxylation- makes pre- procollagen
Cleavage produces tropo collagen
Cross linking produces collagen
What is ehlors danlos syndrome?
A defect in collagen synthesis. Wound healing is poor and patients are subject to joint dislocation
What is osteogenesis imperfecta?
A defect in collagen I. Too little bone tissue and skeletal fragility. Blue sclera are also seen as there is not enough collagen in sclera.
What is alport syndrome?
X linked defect in type IV collagen. Results in dysfunction of glomerular basement membrane, cochlea of ear and lens of the eye. Patients present with haematuria which progresses to chronic renal failure
What is epidermal growth factor?
Has mitogenic effects on epithelial cells, hepatocytes and fibroblasts. Produced by keratinocytes, macrophages and inflammatory cells. Binds to epidermal growth factor receptor.
What is VEGF?
Vascular endothelial growth factor- induces vasculogenesis and angiogenesis, chronic inflammation and wound healing
What is platelet derived growth factor?
Stored in platelet alpha granules and released on platelet activation. Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes.
What is tumour necrosis factor?
Induces fibroblast migration, fibroblast proliferation and collagenase secretion.
What is contact inhibition?
Normal cells will replicate until they have no cells surrounding them and then stop, so that they form a monolayer sheet of cells with no overlap. Cells adhere to each other and the ECM by adhesion molecules.
How do cells bind to each other?
How do cells bind to the ECM?
How does healing by primary intention occur?
Occurs in incisional, closed, non infected and sutured wounds.
Haemostasis- space fills with clotted blood
Inflammation- neutrophils appear
Migration of cells-macrophages appear and scavenge dead neutrophils. These release cytokines which attracts fibroblasts and endothelial cells.
Granulation tissue forms
Fibroblasts proliferate and deposit collagen.
Regression of vascualr channels causes scar to form.
How does healing by secondary intention occur?
Seen in excisional wounds with tissue loss and separated edges, or infected wounds.
Open wound is filled with granulation tissue
More intense inflammatory reaction
Myofibroblasts contract the wound.
How do bone fractures heal?
Haematoma fills the gap
Granulation tissue forms.
Platelets and inflammatory cells release cytokines. This activates osteoclastic and osteoblastic activity
A soft callus is formed of fibrous tissue and cartilage within which woven bone begins to form.
A hard callus is laid down by osteoblasts formed from woven bone
Woven bone is reorganised into lamellar bone due to the mechanical stresses placed upon it.
Which factors influence healing and repair?
Size/location/type of wound
What are the complications of fibrous repair?
Adhesions can form
Loss of function due to scar tissue
Disruption of tissue architecture
How does healing and repair occur in cardiac muscle?
Very limited capacity—> MI is followed by scar formation.
How does healing and repair occur in the liver?
Very good capacity —> if part of the lvier is removed there is compensatory overgrowth of liver tissue in other lobes
How does healing and repair occur in peripheral nerves?
The ends of the nerves regress by wallerian degeneration. The proximal stumps of the degenerated axons sprout and elongate, then they use the schwann cells to guide them back to the tissue that the nerve innervates.
How does healing and repair occur in cartilage?
Does not heal well as it lacks blood supply, lymphatic drainage or innervation