pathogenesis of infectious and anti-inflammatory disease Flashcards
summarise the natural defences of the ocular surface
how can these mechanisms become compromised?
antimicrobial preterites of tears, constant shedding of cells of ocular surface which reduces contact time with pathogens
imunonosupressed px, corticosteroid use, ocular surface disease, CL wearers
what viruses can effect the ocular surface?
Adenovirus
Herpes simplex
Cytomegalovirus (CMV)
Varicella zoster virus (VZV)
what are normal conjunctival flora/commensals?
*Variety of non-pathogenic bacteria are present on the eyelids and conjunctiva
*Called commensals
*Part of the defence of the eye: these bacteria compete with potential pathogens for nutrients
*Viruses and fungi are uncommon residents, so cornea doesn’t contain commensals for them
*Commensals are normally gram-positive bacteria and uncommonly environmental fungi
what bacteria are commonly resident on the lids and conjunctiva?
-gram positive cocci:
-staph epidermis
-staph aureus
-micrococcus
gram positive bacilli:
-corynebacterium species
anaerobic:
-propionibacterium
what part of the eye is bacterial colonisation greater and why?
Bacterial colonisation is greater on lid margin due to washing action and antimicrobial action.
what peri-ocular infections of the eyelid can you get?
external hordeolum
internal hordeolum
blepharitis
pre-septal cellulitis
orbital cellulitis
what is an external hordeolum?
what are the signs?
what bacteria cause it?
what is the treatment?
what is an internal hordeolum?
*Infection of glands associated with the base of eyelashes including sebaceous glands of Zeis
*Characterised by lid swelling, redness, tenderness, pustule (collection of pus under the skin)
*Common bacteria that cause this: staphylococcus species: staph. Aureus
*Stye treatment: warm compresses, topical antibiotics
*Internal hordeolum: meibomian glands infected
what species cause belpharitis?
is it infective?
*Staphylococcus species: staph. Aureus, staph. Epidermis
no
tell me about staphylococci
gram + or -?
shape?
what does it cause?
how do they produce damage?
*Commensals on human skin
*Gram positive
*Spherically shaped bacteria that aggregate in clusters
*Grow on most media
*Can cause ocular surface infections like conjunctivitis
*Can cause severe infections if gets deeper into the eye
*Systemically are a common cause of food poisoning
*Produce damage by production of toxins resulting in cell damage and instruction
who is pre septal/orbital cellulitis most common in?
why is orbital cellulitis life threatening?
what are the signs?
what is the aetiology?
what is the treatment?
children
Arises from an abscess in sinuses, particularly ethmoid sinus which spread into orbit
There is direct communication between orbital and cranial cavity. Infection can track into grey.
proptosis, lid swelling, limitations of eye movements, pain on eye movement, associated RAPD
sinusitis (80-90%)
step pneumoniae/H. influenzae
same day referral
intravenous antibiotics even before CT scan
surgery to drain abcess
tell me about streptococci
gram + or -?
shape?
what do they cause?
what agar do they grow on?
how do they cause disease?
*Gram positive spherical bacteria
*Form distinctive chains
*Commensals of mouth/gut. Many are non-pathogenetic
*Can cause conjunctivitis or orbital cellulitis
*Can cause pneumonia, wound, and skin infections, sepsis and endocarditis)
Grow on blood agar. (Haemolysis: breaks down blood)
Toxin mediated disease
tell me about haemophilus spp
gram + or -?
shape?
what type of pathogens are they?
commensals of the…
grow on what agar?
what do they cause?
*Gram negative rods
*Most strains of haemophilus influenza are opportunistic pathogens (live in host without causing problems. When other factors liked reduced immune function or chronically inflamed tissues create opportunities for infections.)
- Commensals of the upper respiratory tract
- Grow on chocolate agar (variants of blood agar)
- Common cause of conjunctivitis especially in children with sinusitis
- Can cause pneumonia and meningitis systemically
what is the most common eye infection?
what ages does conjunctivitis effect?
what types can you get?
conjunctivitis
most common in children.
Neonatal ophthalmia: occurs in early years of life, swabs would be taken if failing to respond to broad spectrum antibiotics. Need to be referred
viral, bacterial, chlamydial
what are the characteristics of bacterial conjunctivitis?
what are the signs?
what bacteria causes the acute form?
what bacteria causes the chronic form?
Characteristics
*Usually bilateral after 1-3 days although one eye may proceed the other.
*Rapid onset
*Self-limiting infection
*Caused by staphylococci/streptococci/H. influenzae
Signs
*Pus like discharge
*Eyelids being stuck together on waking up
Acute
■ Staphylococcus aureus (children & adults)
■Strep. Pneumo / H. influenzae (children)
Chronic
■Due to exotoxins
■ Staphylococci / Moraxella / Enterobacteriacae
■ May be difficult to eradicate
what is viral conjunctivitis most commonly caused by?
what are the signs?
what complications can you get of adenovirus?
Most commonly caused by adenovirus sub types
*Commonly associated with cold and flu
*Associated with enlargements of the pre-auricular nodes (Infront of ear)
*Follicular response of tarsal conjunctiva
*Self-limiting (a few days-couple of weeks)
*Usually resolves without any complications
Complications caused by adenovirus :
Pharyngoconjunctival fever
*More common
*associated with upper respiratory tract infection
*resolves within 2 weeks
*pharyngitis/conjunctivitis/fever
epidemic keratoconjunctivitis
*more severe
*lasts for 1-3 weeks
*associated subconjunctival haemorrhages 33%
*may get corneal involvement: 20-30% sub-epithelial infiltrates
what type of virus is adenovirus?
how does it cause disease?
*DNA virus
*Spread by secretions following coughing and sneezing
*Can survive on inanimate objects (fomites) and transmitted to the eye through eye/hand contact
what 2 from does chlamydial conjunctivitis cause?
trachoma
inclusion conjunctivitis
where is trachoma more common?
what are the signs?
what is the treatment?
*Trachoma is endemic in developing countries (due to overcrowding and poor sanitation)
Common in South America, Africa and parts of Asia, indigenous comminates
*Causes palpebral conjunctival scarring
*Causes entropion, extropian, leads to exposure of ocular surface with extensive scarring. Blinding condition.
*Treatment: antibiotics of tetracycline variety, Erythromycin, Azithromycin
who does inclusion conjunctivitis occur in ?
what is it associated with?
what are the signs?
*Affects adults
*Associated with STD’s.
*Involves cornea: punctate keratitis with sub epithelial infiltrates
*Unilateral red eye
*Usually mild/diffuse
*Chronic follicular conjunctivitis (often mis-diagnosed as bacterial infection)
what is chlamydiae?
how can you diagnose it?
*Obligate intracellular parasite
*Depend on host cell
*Inert infectious particles
*Are a type of bacteria
serology, histology, PCR
how can you measure antibiotic sensitivity?
what agars can you get?
*Uses antibiotic impregnated paper discs which are plated onto agar plate.
* Bacteria is allowed to grow on the plate.
*By measuring zone of inhibition of bacterial growth will indicate most effective antibiotic against that bacteria
chocolate agar
blood agar
Mc conkey agar
sabouraud dextrose agar
what is the most common type of keratitis?
what bacteria cause it?
what bacteria are more common for keratitis in contact lens wearers?
bacterial
■ Pseudomonas sp. (Gram -ve)
■ Staphylococcus sp. (Gram +ve)
■ Streptococcus sp. (Gram +ve)
gram -
what are the risk factors for microbial keratitis?
- Contact lens wear (higher incidence for overnight soft cl wear, poor lens hygeine)
- Immunosuppression
- Ocular surface disease
- Trauma
what is a sign of herpetic keratitis?
HSV-1 causes?
HSV-2 causes?
what does varicella zoster virus cause?
dendritic ulcer
HSV-1: herpes simplex cold sores.
HSV-2: genital herpes
Varicella zoster virus causes chickenpox in children but in adults it causes shingles. When it effects ophthalmic division of trigeminal nerve: causes corneal involvement in 65% of cases
what are the mechanisms of bacterial pathogenicity?
*Some produce damage through the colonisation of the body surface and release toxins. They only invade the tissue to a limited extent.
*Some cause damage by invasion and subsequent multiplication in tissues
what causes non-infections keratitis?
what is marginal keratitis?
how is it managed?
toxin mediated. corneal response to toxins. e.g., CLARE
*Non-contact lens wearers
*Increased colonisation on lid margins
*Associated with lid margin disease
*Inflammatory response to bacterial toxins on lids
*Non-infective
*Managed by topical steroids, topical antibiotic, lid hygiene
What is CLPU?
what are the signs?
what is the treatment?
contact lens peripheral ulcer
*localised.
* Important to differentially diagnose from bacterial keratitis.
*Infiltrate is much smaller
*associated with damage to underlying epithelium
*Peripherally just inside the limbus.
* Less than 1 mm in diameter.
- Can be managed in optometric practice
- Treatment: discontinuing of contact lens wear until condition resolves.
what causes uveitis?
what are the different types?
most cases are non-infective.
inflammatory aetiology or idiopathic
*Classified as anterior (iris and pars plicata of ciliary body), intermediate (pars plana of ciliary body), posterior (choroid), panuveitis (inflammation extends throughout uveal tract
what is the infectious aetiology for anterior uveitis?
posterior uveitis?
what is endophthalmitis?
what are the classifications?
what is the treatment?
Anterior
* Herpes simplex virus (HSV)
* Varicella zoster virus (VZV)
Posterior
* Toxoplasmosis (parasites)
* Toxocara (worm infection)
* Syphilis
* Cytomagalovirus (CMV) (immunosuppressed px)
*Serious ocular condition when internal
*Structures are exposed to exogenous organisms (bacteria)
*Result of trauma or penetrative surgery
*Acute post-cataract
*Chronic pseudo phakic
*Bled-related posttraumatic
Treatment:
high dose antibiotics injection into eye, sight threatening
what is inflammation?
what is the purpose of inflammatory cells?
what are the causes of inflammation?
how is inflammation classified?
Response of living tissue to damaging stimuli
Purpose of inflammatory response is to direct immune components (cells, soluble mediators) to site of damage
Contains the damage and initiates repair to restore normal function.
Causes of inflammation:
Infection (stye of lid margin)
Hypersensitivity reactions (inappropriate inflammatory response)
Autoimmunity
Trauma (including iatrogenic-from surgery)
Chemical/toxic
Radiation
Classification of Inflammation
acute: Short duration (minutes or days)
chronic:Long duration (weeks or months)
Can be secondary to acute
What are the major features of acute inflammation?
*Vascular and cellular events triggered by inflammatory mediators:
-vasodilation: redness
-Increased blood flow: heat
-Increased vascular permeability: oedema associated with inflammation
How does movement of inflammatory cells from blood vessels to sight of injury to minimise damage and initiate repair process?
*Neutrophils are first cell to appear in acute inflammatory response.
Extravasation of leukocytes into tissues (exudate)
*Cells move from centre of blood column to endothelial wall of blood vessels. Called MARGINATION.
*This is due to influence from inflammatory mediator
*Adhesion molecules are expressed by the endothelium which allows inflammatory cells to attach
*It then rolls along the vessel wall before coming to rest: ROLLING
*The cell then squeezes through the vessel: DIAPEDESIS.
*Once the cells leaves the vessel, it moves along the concentration gradient of inflammatory chemicals released from the site of inflammation: CHEMOTAXIS.
what is the purpose of phagocytosis?
how does it happen?
*Role is to eliminate potential pathogens or damaged tissues
*Phagocytes arrive at the site of inflammation by chemotaxis
*Microorganisms or cell debris are recognised by specific receptors
*Phagocytes attach to microorganisms, cell debris or foreign material via surface receptors
*Material internalized and destroyed in a controlled manner
*Phagocytosis is enhanced by the antibodies and the complement system of proteins
*Proteins coat the particles to be phagocytosed
*Phagocytes have antibody complement receptors on their surface that enhance the bind of the cell to its target. This is called opsonisation. Antibody and complement components are called opsonins.
what are the inflammatory mediators?
*Vascular and cellular events are under the control of soluble chemical mediators
*Consist of certain chemicals produced by immune or inflammatory cells e.g., Vaso amines produced by mast cells and basophils, cytokines produced by lymphocytes
*Other mediators: complement, kinins found in plasma. These are protein.
Important source of inflammatory mediators is the arachidonic acid pathway. Produces prostaglandins, leukotrienes, and other mediators
what are the inflammatory mediators produced by eicosanoid synthesis called?
how does the pathway work?
eicosanoids
1.Conversion of phospholipids in plasma membranes to arachidonic acid under action of the enzyme phospholipase A2.
2. arachidonic acid is converted into inflammatory mediators
3.lipooxygenase (Locks) converts arachidonic acid into leukotrienes
Cyclo-oxygen (Cox) converts arachidonic acid into prostaglandins, thromboxane A2, prostacyclin.
where are most cell mediators found in the eye?
what is their role?
what do mast cell mediators contain?
how do they cause inflammation?
numerous in conjunctiva
in initiation of type 1 hypersensitivity reaction
contain granules containing pre-formed vasoactive mediators like histamine and heparin
*Upon stimulation, mast cells release these granules. This is called degranulation.
*Release of mediators contained in granules causes vasodilation and increased vascular permeability
*Sensory nerves also contain histamine receptors-can produce itching on skin or eye
*Feature of hay fever and urticaria
*After degranulation mast cell initiates a delayed 2nd phase response. This is characterised by the synthesis of newly formed mediators produced by arachidonic acid pathway (leukotrienes LTD4, LTC4, prostaglandin D2 and platelet activating factor)
what are the outcome of acute inflammatory response?
wha ocular responses can you get to inflammation?
1.Complete resolution
2.Scar formation
3.Progress to chronic inflammation (lymphocytes, macrophages)
redness, oedema, papillae/follicles, exudates, cellular infiltration, discharge
what causes oedema?
how do you differentiate between papillae and follicles on tarsal conjunctiva?
increased vascular permeability
papillae are reddish flat top raised lesions.
- Tarsal plate looks red and velvety.
-each papillae consists of a dilated blood vessel at the centre surrounded by lymphocytes. Covered by hypertrophic epithelium.
-follicles are greyish, round, elevated structures consisting of aggregation lymphocytes with a modification of the overlying epithelium.
what types of discharge can you get?
- Serous: watery
- Mucopurulent: mucus and pus
- Purulent: pus
what cells infiltrate in acute and chronic inflammation?
- Acute inflammation: neutrophils
- Chronic inflammation: influx of inflammatory cells (lymphocytes and macrophages)
how do you get keratic precipitates?
what is flare in anterior uveitis? what signs does it cause?
Inflammatory cells leave vascular system and circulate in the aqueous humour. They deposit as clumps on corneal endothelium and are called keratic precipitates.
protein molecules entering aqueous humour due to breakdown of blood aqueous barrier causing light scatter
what diseases show signs of inflammation of posterior segment?
what is anterior ischaemic optic neuropathy?
what is it a complication of?
anterior ischaemic optic neuropathy
sarcoidosis
*Swollen optic disc caused by vasculitis.
Blood vessel wall of blood vessels suppling disc suffer inflammatory reaction with a gradual reduction in the size of vascular lumen, leads to optic head ischaemia.
temporal arteritis
what does sarcoidosis cause?
*epithelial granulomatous tissue accumulates in a variety of organs including the eye. Produces keratitis and associated retinitis
what is autoimmunity?
what is their genetic susceptibility?
immune system attacks normal body tissues due to breakdown of self-tolerance.
People can have genetic susceptibility to autoimmunity by having HLA haplotypes like HLA B 27.
what is mooren’s ulcer?
what is it caused by?
what other disease it causes by autoimmunity?
peripheral corneal ulcerative keratitis occurs causing progressive thinning of peripheral cornea
Organ specific autoimmune disease (just effect the eye)
Sympathetic ophthalmia
-following penetrating injury to one eye followed by development of inflammation in the other eye within 3 weeks to 1 year of the initial event
what ocular autoimmune diseases can you get with systemic involvement?
- Reiter’s disease
- Ankylosing spondylitis: uveitis
- Rheumatoid arthritis: dry eye
- Behçet’ disease
- SLE
- Sjögren’s syndrome
- Sarcoidosis
- Cicatricial pemphigoid
what is the pathogenesis of allergic eye disease?
Allergic eye disease is caused by Type I or Type IV hypersensitivity reactions
Acute allergic conjunctivitis and seasonal allergic conjunctivitis are classical examples of a Type I hypersensitivity reactions
Atopic allergic conjunctivitis, giant papillary conjunctivitis and vernal are mixed Type I and Type IV reactions
Conjunctival medicamentosa is principally a Type IV reaction
what is type 1 hypersensitivity?
what are ocular examples?
what is it caused by?
*Also referred to as atopy
*Most common
*Mast-cell mediated hypersensitivity
*Occurs within minutes of exposure to a variety of environmental antigens
*Common ocular example: seasonal or perennial allergic conjunctivitis
*Strong genetic link
*Caused by overproduction of IgE
what is the mechanism of type 1 hypersensitivity?
*Mast cells display a high affinity receptor for IgE
*IgE is synthesised in response to certain antigens (allergens)
*Allergens are deposited on mucous membranes and taken up and processed by antigen presenting cells, e.g., dendritic cells.
*Allergen is presented to T helper 2 cells.
*TH2 cells provide cytokine signals to B cells to produce IgE.
*Once synthesised, IgE binds to mast cells.
*Following the first exposure to antigen, the patient is asymptomatic.
*Following 2nd and all after that exposure, antigen causes crosslinking of the IgE which are bound to the surface of the mast cell. Causes mast cell degranulation.
*Degranulation of mast cell produces symptoms of acute allergic reaction.: itching, mucous secretion, vasodilation, and oedema.
*Mast cell mediators include vasoactive chemicals like histamine and heparin
what is type 2 hypersensitivity?
- Antibody mediated hypersensitivity
- Antibody is directed against cell surface antigens
- Antibody can activate complement which produce membrane damage directly by complement mediated cell lysis.
- Certain complement components attract phagocytes which bind to antibody via Fc receptor.
- Attempted phagocytosis of target cell produces further tissue damage through release of proteolytic enzymes.
what is type 4 hypersensitivity?
- Delayed type hypersensitivity
- Take more than 12 hours to develop
- Mediated by T cells
what is the mechanism of type 4 hypersensitivity?
- antigen presenting cells (APC) resident in conjunctiva process antigen and migrate to regional lymph nodes where they activate t cells
- Sensitised T cells migrate back to the conjunctiva where they produce cytokines which attract macrophages which causes tissue damage
