Tissue damage and Inflammation Flashcards
causes of tissue damage (7)
ishaemia / infarction
trauma
tempeerature changes
light exposure
chemical injury
dysregulated immunity
nutiritaonl damnage
how does ischemia cause tissue damage
reduced oxygen supply
how does trauma cause tissue damage
usually mechanical
zonular rupture - lens discloation
ciliary muscle disinsertion - leads to TM collapse and angle recession glaucoma
how does temeprature cause tissue damage
e.g. cryotheraphy causing adherive scar
how does light expsoure cause cell damage
UV generally leads to overproduction of free radicals by photons
Corneal epithelium damage in snow blindness
Photoreceptor bombardment with photons
alkali injury
causes liquefactive necoriss
coagulates conjunctival blood vessels –> procealin white is due to limbal ischaemia
penetrates the corneal easliy
kills lens epithelium and causes sevre non-granulomatous iridocyilits
acid injury
causes coagulative necorsis
less desctrictuve
Argon laser
Wavelength: 485 - 514
Mechanism: photocoag
Use: coag from the chorocapillaris to the neuclear layer
frequency double Nd-YAG laser
Wavelength: 532
Mechanism: photocoag
Use: safer than argon for mac laser
diode laser
Wavelength: 810
Mechanism: photocoag
Use: ROP, retinal photocoagulation, destruciton of the CB
photodynamic laser therapy
Wavelength: 689
Mechanism: photoradical
Use: chorodial vascular pahtology e/g/ haemoagiams
Nd-YAG laser
Wavelength: 1064
Mechanism: photodisruptive
Use: YAG PC, P
excimer laser
Wavelength: 193
Mechanism: photoablation
Use: refractice surgery
femto laser
Wavelength: 1053
Mechanism: photoablation
Use: refractice surgery
PRP laser
destroys localished patches of the outer retina and RPE
reactive proliferation of RPE aorund white cirel (glial cell) = scar
transpupillary thermotherapy
IR to heat to 40degrees chorodial melanoms to bring about cell necrosis
acid injuriew
coagulative necorsis
alkali injuries
liquefactive necrosis
coagulates conjunctival blood vessels: “porcelain white” appearance
Widespread limbal ischaemia and destruction of limbal stem cells
drusen
PAS positive structure, found betwen the RPE and bruchs membrane
transiet strutures
4 types: hard, soft, basal and calcific
hard drusen
Well-demarcated
PAS-positive
Made of hyaline
soft drusen
Poorly defined
Represent removal of RPE from the Bruch membrane
basal drusen
Diffuse small drusen found in the macula
calcific drusen
Refractile drusen found near areas of RPE atrophy.
reticular pseudodrusen
Found between inner segment and outer segment (IS/OS) junction and RPE
Associated with the transition to advanced forms of AMD i.e. geographic AMD.
Made of extracellular material
pseudodrusen on FAF
Reduced signal from blocking and increased the signal from RPE distress.
mechanisms of cell death
- necorsis = death of a group of cells, always pathological
- apoptosis = programmed cell death
reversible injury
- hydropic swelling - cell becomes swollen, usually 2nd to trauma
- atrophy - decrease in cell size and number
acute inflammation
Reaction to injury be it physical, chemical, infective, immunological
Vascular phase followed by cellular phase
classic signs of acute inflammation
Classic signs: redness, heat, swelling, pain, loss of function
Hyperaemia: initial vasoconstriction then dilation
Vasodilation slows blood flow causing cells to move to the sides (margination)
Exudation: protein-rich fluid moves into interstitial fluid (dilutes toxins)
Leucocyte migration for phagocytosis: extravasation and chemotaxis
Non-adaptive, no memory, non-specific
duration of acute inflammation and outcome
lasts 1-2 days
resolve (if no tissue destruction and exudate is removed),
suppurate,
repair with organisation/scarring (if the exudate persists),
progress to chronic
inflammation.
If tissue is destroyed, regeneration can occur if the lost cells are labile or stable. If permanent cells are lost, a vascularised connective tissue scar forms
chemical mediators in vascular pahse
Histamine: from degranulated mast cells. Increases vascular permeability (C3a and C5a) and vasodilation of venules. Short-term effect (5-15 minutes)
Kinins: more prolonged venule and capillary vasodilation response
Prostaglandin: dilates arterioles. More persistent response (4-24 hours)
cell type on bacterial infection
bacterial
cell type on parasitic infection
eosinophil
cell type in viral infection
monocytes
neutrophil rolling
Bonds are established (by selectins on endothelium and integrins on neutrophils) between endothelium and white cells following margination
(normally, both neutrophils and endothelium have negative charge and so do not contact)
platelet activaition
Platelet activating factor activates neutrophils and induces beta-integrins
expression on their cell membranes which further promote adhesion with the endothelium
trigger for migration of neutrophils
ransmigration of the neutrophils between endothelial cells then occurs,
stimulated by IL-8
chemotaxis
following transmigration, the movement of cells is mediated by
chemotaxis, along the concentration gradient of chemotactic agents.
It is the directional and purposive movement of phagocytic cells towards areas of injury/invasion
steps in chemotaxis
o Reception of signals
o Response to signals (transduction)
examples of chemotaxis
o Cytokines from other leucocytes
o Complement components (C5 and C5a)
o Arachidonic acid derivatives (eicosanoids eg. leukotrienes and prostaglandin
E)
o Pathogens
o Lymphokines (produced by T helper lymphocytes)
role of leucocytes
Once within the injured tissue, leucocytes can undertake phagocytosis
Recognition, aided by opsonisation
o Opsonins: IgG and C3b
Bacterium/foreign object engulfed by a phagosome
phagosome
Phagosome fuses with lysosome: associated with the “respiratory burst” of
metabolic activity producing hydrogen peroxide
macrophages
Within tissues, monocytes undergo enlargement, increased lysosome numbers,
Golgi and ER development
macrophage activation
Increased phagocytic capacity
Production of hydrolytic enzymes, pyrogen and interferon (blocks translation of viral mRNA)
Stimulates fibroblast proliferation and further polymorph production
Lymphocytes activating factor (IL-1) stimulates T helper cells
role of macropahges
Stimulated by C3b
Capable of cell division
Contribute to antigen presentation
Can fuse to form multinucleated giant cells (increased phagocytic activity)
Epithelioid cells within granulomas are derived from a single macrophage
(increased secretory capacity)
granulomatous KPs
“mutton-fat” KPs) are composed on
macrophages compared to non-granulomatous KPs which are mainly lymphocytes and PMLs
complement systemt
Involved in acute inflammation, phagocytosis, clotting, immune and
hypersensitivity reactions (C3a and C5a are anaphylatoxins)
what stimulates complement
Classical and alternative pathways are both stimulated by plasmin
components of the complement systtem
C3a and C5a increases vascular permeability as above. C5a is 1000 times more active
C5b joins with C6, C7, C8 and C9 to form the membrane attack complex which is
capable of cell lysis
plasma cascade system
Factor XII (Hageman factor) of the clotting cascade has a central role in activating
3 systems operating within plasma
systems operative within the plasma cascade system
Kinin system (via activating prekallikrein) to produce potent vasodilators
Clotting cascade (via stimulating factor XI)
Complement system (via activating plasminogen to plasmin)
All three have positive feedback loops to activate more Hageman factor
chronic inflammation
Response to persistent pathogen/irritant (need not be infectious)
NB: acute phase does not need to be prolonged (eg. in TB it is very brief)
Cellular response predominates: mixed proliferation and destruction
granuloma
failure of acute inflammatory neutrophils to clear the inciting agent, meaning macrophages take over
Derived from macrophages and their lineage
Caseation is a feature of tuberculous granuloma
structure of granuloma
Inner core of macrophages and epithelioid cells with increased secretory
capacity
Core surrounded by layer of activated macrophages (containing ingested microoganisms) and T lymphocytes
Outer layer containing fibroblasts and multinucleated giant cells
delayed hypersenitivy response and granuloma
Response to breakdown of endogenous materials (eg. chalazion: reaction to
rupture of a blocked meibomian gland duct releasing irritant keratin)
Response to exogenous non-biological materials ie. foreign body
Mainly mycobacteria eg. TB or leprosy and fungi
Unknown eg sarcoidosis (non-caseating)
non-granulomatous inflammation
characterised by lymphocytes and plasma cells
Behcet’s disease
Multiple sclerosis
corneal angiogenesis
Response to inflammation promoted by fibrin and its degradation products
endothelial activation
Endothelial activation (within 24 hours)
Endothelium retracts and nucleoli enlarge
Endothelial basal lamina broken down by plasminogen activator
Produced by fibroblasts, macrophages and others
vascular sprotuing
Sprouts from post-capillary venules and capillaries
Lumen formation and anastomosis of blind channels
vascular maturation
deposition of ECM and laminin and basal lamina formation
latent period
Vasodilation
Vascular permeability of neighbouring vessels
Stromal oedema
tissue damage from ionising radiation
Direct killing of cells ( free radicals release, ionic forms of hydrogen and hydroxyl result in a break in DNA structure)
Cellular DNA changes
Damage to blood vessels leading to secondary ischaemic necrosis
occular manifestataions of damaged from ionising radation
Necrosis of sclera ( can occur with mitomycin C)
Dry eye syndrome ( usually occur with doses of 60-70gy)
Punctate epithelial erosion
Cataracts
radiation induced cataract
( may take up to 20 years after exposure before developing cataract)
Young patients more susceptible as more active lens cells growing .
The lens is the most radiosensitive structure with an average latent period of 2-3 years.
raidation retinopathy
Slowly progressive
Microangiopathic changes can mimic diabetic retinopathy.
4) The delay is usually 2-3 years for radiation optic neuropathy
commotio retinae
Caused by shockwaves from trauma
Induces outer retinal sheen-like whitening
OCT findings
Photoreceptor and retinal pigment epithelium (RPE) disruption
Vision can go down to 6/60
chorodial rupture
Disruption to Bruch’s membrane/RPE
Associated with subretinal bleeding
Usually around optic disc or periphery (occasionally in the macula)
Choroidal neovascularization (CNV) can grow at rupture site.
post-traumatic macular hole
Traumatic vitreomacular traction
Submacular haemorrhage from choroidal rupture
Severe commotio retinae
retinal sclopetaria
Caused by high-velocity projectile injury to the orbit
Causes choroidal and retinal damage
Can present with subretinal, retinal and vitreous haemorrhage
Over time retinal scars will form
