Pathology - inflammation Flashcards
What are some vascular changes that occur in response to injury?
- Changes in flow and vessel caliber and vasodilation
- These first involve arterioles and then capillary beds
What chemicals mediate vasodilation and what is the result of vasodilation?
Mediated by histamine and nitric oxide and results in increased heat (calor) and redness/erythema (rubor)
What are some cellular changes that occur in response to injury?
Stasis, white cell margination, rolling, adhesions, migration
How is white cell margination able to occur after injury?
Vasodilatation occurs which slows the rate of blood flow making cells able to move peripherally - especially larger white cells
Name some chemical mediators that are expressed after injury
- Selectins - expressed on endothelial cell surface
- Integrins - bind to vessel walls, cell matrix and other cells
- Vascular cell adhesion molecule (VCAM)
- Intercellular adhesion molecule (ICAM)
What chemicals cause release of inflammatory mediators in cells?
- Histamine and thrombin increase selectin expression
- TNF and IL-1 increase endothelial expression of VCAM and ICAM
What substance increaes the affinity of VCAMs and ICAMs for integrins?
- Chemokines from the site of injury bind to proteoglycans on endothelial cell surface.
- These proteoglycans then increase the affinity of VCAMs and ICAMs for integrins
What happens as a result of vascular permeability in response to injury?
- Leaky blood vessels - loss of proteins
- Change in osmotic pressure - water follows protein - swelling
What happens in chemotaxis?
Cells follow a chemical gradient and move along it
What are the 3 phases of phagocytosis?
- Recognition and attachment
- Engulfment
- Killing and degradation
What is involved in the recognition and attachment stage of phagocytosis?
- Mannose receptors
- Bacterial surface glycoproteins and glycolipids contain terminal mannose residues.
- Mammalian glycoproteins and glycolipids do not
- Scavenger receptors - similar to mechanism that phagocytes recognise low density lipoprotein
- Opsonins - bacteria etc are coated with proteins making them stand out, include components of the complement cascade as well as Ig
What is involved in the engulfment stage of phagocytosis?
- Pseudopods
- Vesicle formation - phagosome
- Joins with lysosome - phagolysosome
What is involved in the killing and degradation stage of phagocytosis?
- Reactive oxygen species
- NADPH oxidase - oxygen gains an electron from NADPH and becomes superoxide
- Reactive nitrogen species
- Nitric oxide synthase - combines NO with superoxide and produces ONOO
What are the clinical features of inflammation according to Celsus?
Rubor (erythema), calor (heat), tumor (swelling), dolor (pain) and loss of function
What mediates the pain/dolor part of the inflammatory response?
Prostaglandins and bradykinin
What is the main cell of acute inflammation?
Neutrophil
What is the resolution stage of inflammation?
Complete restoration of the tissue to normal after removal of inflammatory components
What is needed for effective resolution?
- Minimal cell death
- Tissue has capacity to repair (e.g. GI tract frequently replaces epithelium)
- Good vascular supply
- Injurious agent easily removed
What is suppuration?
- Pus - contains living, dying and dead cells, neutrophils, bacteria and inflammatory debris (fibrin)
- May be termed an abscess
When a space is filled by pus and walled off what is it called?
An empyema
When does organisation occur as part of the inflammatory process?
Mucosa where damage goes beyond the basement membrane favours healing by organisation and repair, not resolution
When can resolution occur as part of the inflammatory healing process?
- Erosions and abrasions describe injury with basement membrane intact.
- These heal rapidly with complete resolution
How is granulation tissue formed?
- Defect is slowly infiltrated by capillaries and then by myofibroblasts
- Deposit collagen and smooth muscle cells
- Given constituents it looks very red
What happens when there is too much scarring and fibrosis of the liver?
- Cirrhosis occurs - results in liver failure
- The liver has some regenerative capacity but can be overwhelmed
What happens as a result of liver cirrhosis?
- Liver failure - loss of liver function, can’t remove toxins and can’t make any proteins
- Plus, large volume of blood flows throughout the liver so can result in vascular disturbances
What factors favour chronic inflammation?
- Suppuration
- Persistence of injury
- Infectious agent e.g. virus
- Type of injury - autoimmune, transplant rejection
What is a granuloma?
Aggregate of epitheloid histiocytes
What can cause granuloma formation?
- Foreign bodies:
- Endogenous - keratin, bone, crystals
- Exogenous - talc, asbestos, suture material, oil
- Specific infection, parasites, syphilis
- Mycobacterium - TB
What is the characteristic feature of a granuloma caused by TB?
Caseous necrosis - cheesy necrosis
How does hypoxia cause cell injury and then acute inflammation?
- No oxygen = No ATP
- No ATP:
- Na/K ATPase fails -> increased K + swelling
- Ca pump fails -> increased intracellular Ca
- increased Ca stimulates; ATPase, phospholipase (membrane damage), proteases (membrane and cytoskeleton damage), endonuclease (DNA damage and breakdown) and mitochondrial permeability (release pro death factors)
What are the first signs in cells after an MI?
- Cells shrink, become red, nucleus shrinks and becomes dark
- Marginal contraction bands appear
What happens in the first 24 hours following an MI?
Cell contents leaked, complement cascade initiated and acute inflammation
At what point is the heart most susceptible to cardiac rupture post-MI?
- 3-7 days post-MI
- Necrosis and neutrophils may be all that is holding it together if the full thickness is affected
What happens after the acute inflammation response to an MI (48 hours)?
- Resolution, restitution and chronic inflammation
- As time progresses, neutrophils fade and are replaced by macrophages
- At this point definite changes can be seen at autopsy - presence of macrophages causes a yellow appearance
Would resolution ever occur after an MI?
- Only if it was short lived and if the injury was mild and blood supply was good
- MI - blood supply is by definition poor, generally once cell death has occurred resolution is unlikely
Describe the process of restitution after an MI
Progressive scarring - macrophages fade and are replaces by fibroblasts
How long after an MI do fibroblasts start to work?
Occurs progressively after 2 weeks and is complete at 6 weeks, so if an MI occurred more than 6 weeks ago it is impossible to date it i.e. could be 7 weeks or 7 years
What is the issue with scarring of the heart post-MI?
- Scar tissue has replaced an area of muscle so the muscle can’t function as well which results in a weaker heart -> heart failure
- Scar tissue can also damage the nerves innervating the heart causing ineffective pace making
