Pathology Flashcards
VINDICATE
V = vascular I = infectious/inflammatory N = neoplastic D = drugs/toxins I = idiopathic C = congenital/developmental A = autoimmune T = trauma E = endocrine/metabolic
What sort of things can cause inflammation?
infection, trauma, foreign bodies, immune reaction, necrosis
Vascular changes:
- What vascular changes are there?
- What are vascular changes mediated by?
- What do vascular changes result in?
- changes in flow and vessel caliber, vasodilatation, vasoconstriction
- mediated by histamine and nitric oxide
- they result in calor (increased heat) and rubor (redness/erythema)
What do cellular changes involve?
Stasis, white cell margination, rolling, adhesion and migration
Changes in blood flow in response to injury
Normally blood flows centrally within a vessel quite quickly. When vascular dilatation occurs, the rate of flow slows and cells can move peripherally, especially larger white cells resulting in white cell margination.
Why do blood cells stick to vessels in inflammation?
Normally the blood vessels are slippy and blood doesn’t stick, however, in inflammation the vessels express various proteins on the luminal surface which have a matching protein on the white cell surface and the white cells stick through a lock and key mechanism with ligands
Examples of proteins on the luminal surface in inflammation
Selectins - expressed on various cells including endothelial cells and white cells
Integrins - over 30 types. Bind to ICAM
Vascular Cell Adhesion Molecule (VCAM)
Intracellular Adhesion Molecule (ICAM)
What happens in inflammation?
- Blood vessels dilate
- Margination, rolling and pavementing - white cell drifting to the side of the vessel. There is still low affinity so the cells bind quickly but are let go quickly
- Chemokines from the site of injury bind to proteoglycans on the endothelial cell surface
- Results in vascular permeability (leaky vessels, resulting in loss of proteins), change in osmotic pressure.
- Water follows protein causing swelling (tumour)
What causes vessels to become ‘leaky’?
Usually from trauma/direct injury e.g. toxins or burns
Endothelial cell contraction - histamine, bradykinin, substance P, leukotrienes
White cells - self harm
Transcytosis - vascular endothelial growth factor mediated. cells squeeze themselves between the vessels
New vessel formation - VEGF makes new vessels but increases leakiness
Chemotaxis
When cells move along a chemical gradient
What is the chemical gradient in chemotaxis made up of?
Bacterial components, complement, leukotrienes and cytokines
3 stages of phagocytosis
- recognition and attachment
- engulfment
- killing and degradation
What contains mannose receptors?
Bacterial surface glycoproteins and glycolipids contain terminal mannose residues
Opsonins
Bacteria etc are coated with proteins making them stand out from the crowd.
Include components from the complement cascade as well as immunoglobulin
Describe engulfment in phagocytosis
Pseudopods ‘catch’ bacteria and vesicle formation occurs (phagosome). Phagosome joins with lysosome to form phagolysosome
What is killing and degradation performed by?
Reactive oxygen species or reactive nitrogen species
Clinical features of inflammation
Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain) and sometimes loss of function
What is rubor caused by?
Increased perfusion with slow flow rate and increased vascular permeability
What is calor caused by?
Increased perfusion with slow flow rate and increased vascular permeability
What is tumor caused by?
Vascular changes
What is dolor mediated by?
Prostaglandins and bradykinin
What is the inflammatory cell that characterises acute inflammation?
Neutrophil - sometimes called polymorphs because there are many lobes in nucleus. Granulocytes and have both phagocytic and cytotoxic properties
What 4 options are there after acute inflammation?
- Resolution
- Suppuration
- Repair, organisation and fibrosis
- Chronic inflammation
When are mediators of inflammation produced?
Only for as long as the stimulus persists
How long do neutrophils survive outside the blood vessel?
Only a few hours
What does the degree of healing after inflammation depend on?
Site of injury - different organs have different capacities for repair due to different vascular supplies
Type of injury - severity, pathogenicity of organism
Duration of injury - can it be removed? is it sustained?
Resolution
Complete restoration of the tissue to normal after removal of inflammatory responses
When is resolution most likely to occur?
- minimal cell death
- tissue has capacity to repair (e.g. GI yes, CNS no)
- good vascular supply (delivery of white cells and rapid removal or injurious agents)
- injurious agents are easy removed (cuts/wounds cleaned)
Suppuration
Formation of pus or noun for pus. Contains living, dying and dead cells, neutrophils, bacteria and inflammatory debris. AKA abscess
Organisation
Scarring
When is organisation more likely to occur?
- if injury produces lots of necrosis
- if injury produces lots of fibrin not easily cleared
- poor blood supply (cannot remove debris)
- tissue type
- damage is deep - mucosa where damage goes beyond the basement membrane favours healing by organisation and repair rather than resolution
What type of injuries are erosions and abrasions?
Injuries where the basement membrane is still intact. These heal rapidly with complete resolution. Superficial injuries
What is a common response in all tissues in healing?
Granulation tissue formation
Granulation tissue
Defect is slowly infiltrated by capillaries and then myofibroblasts.
There are deposits of collagen and smooth muscle cells
It looks very red due to constituents
New vessels come in from side and they are leaky
What is chronic inflammation characterised by?
Lymphocytes (small round blue cells) and macrophages are sometimes present
When is chronic inflammation favoured?
- if there is suppuration - walled off pus, scarring
- persistence of injury - foreign material, keratin
- infectious agent - virus, persistence of infection
- type of injury - autoimmune e.g. transplant rejection
Granulomas may be seen in the presence of what?
Foreign bodies, endogenous substances (bone, keratin, crystals), exogenous substances (talc, asbestos, suture material), specific infections, parasites, worms, eggs, syphilis, mycobacterium (TB)
What is a granuloma?
An aggregate of epitheliod histiocytes
Which type of necrosis occurs in the presence of tuberculosis granulomas?
Caseous necrosis
Infarction
Death of tissue after loss of oxygen
How does hypoxia cause cell injury and acute inflammation?
No oxygen means no ATP
Na/K ATPase fails and increased K means swelling
Calcium pump fails therefore increased calcium
>Calcium stimulates ATPase (inhibits ATP), phospholipase (membrane damage), proteases (membrane and cytoskeleton damage), endonuclease (DNA damage and breakdown), mitochondrial permeability (release pro-death factors)
How long is the safety window of inflammation (e.g. MI) in the myocardium?
20 minute window
First signs of cell death
Cells shrink, become redder, nucleus shrinks and becomes darker, marginal contraction bands appear