
## Acute inflammation
<ul>
  <li>Reaction to injury be it physical, chemical, infective, immunological</li>
  <li>Vascular phase followed by cellular phase</li>
  <li>Classic signs: redness, heat, swelling, pain, loss of function</li>
  <ul>
    <li>Hyperaemia: initial vasoconstriction then dilation</li>
    <li>Vasodilation slows blood flow causing cells to move to the sides (margination)</li>
    <li>Exudation: protein-rich fluid moves into interstitial fluid (dilutes toxins)</li>
    <li>Leucocyte migration for phagocytosis: extravasation and chemotaxis</li>
    <li>Non-adaptive, no memory, non-specific</li>
  </ul>
  <li>Lasts 1-2 days</li>
  <li>
    Outcome: resolve (if no tissue destruction and exudate is removed), suppurate, repair with
    organisation/scarring (if the exudate persists), progress to chronic inflammation
  </li>
  <ul>
    <li>If tissue is destroyed, regeneration can occur if cells are labile or stable</li>
    <li>If permanent cells are lost, a vascularised connective tissue scar forms.</li>
  </ul>
  <li>Chemical mediators of vascular phase:</li>
  <ul>
    <li>
      Histamine: from degranulated mast cells. Increases vascular permeability (C3a and C5a) and
      vasodilation of venules.&nbsp;
    </li>
    <li>Kinins: more prolonged venule and capillary vasodilation response</li>
    <li>Prostaglandin: dilates arterioles.</li>
  </ul>
  <li>Cellular phase</li>
  <ul>
    <li>Neutrophils predominate in bacterial infection</li>
    <li>Eosinophils predominate in parasitical infection</li>
    <li>Monocytes predominate in viral infection</li>
    <li>Cell adhesion molecules are expressed on activated endothelial cells</li>
    <li>
      Bonds are established (by selectins and integrins) between endothelium and white cells
      following margination (normally, both neutrophils and endothelium have negative charge and so
      do not contact)
    </li>
    <ul>
      <li>So-called neutrophil rolling</li>
    </ul>
    <li>
      Platelet activating factor activates neutrophils and induces beta-integrins expression to
      promote adhesion with the endothelium
    </li>
    <li>Transmigration of the neutrophils between endothelial cells then</li>
    <ul>
      <li>Stimulated by IL-8</li>
    </ul>
  </ul>
  <li>
    Chemotaxis: after transmigration the movement of cells is mediated by chemotaxis, along the
    concentration gradient of chemotactic agents
  </li>
  <ul>
    <li>The movement of phagocytic cells towards areas of injury/invasion</li>
    <li>Steps:</li>
    <ul>
      <li>Reception of signals</li>
      <li>Response to signals (transduction)</li>
    </ul>
    <li>Examples of chemotactics:</li>
    <ul>
      <li>Cytokines from other leucocytes</li>
      <li>Complement components (C5 and C5a)</li>
      <li>Arachidonic acid derivatives (eicosanoids eg. leukotrienes and prostaglandin E)</li>
      <li>Pathogens</li>
      <li>Lymphokines (produced by T helper lymphocytes)</li>
    </ul>
    <li>
      Binding of chemotactic factors on the polymorph stimulates calcium influx leading to increased
      cGMP and microtubule assembly to aid migration
    </li>
  </ul>
  <li>Once within the injured tissue, leucocytes undertake phagocytosis</li>
  <ul>
    <li>Recognition, aided by opsonisation</li>
    <ul>
      <li>Opsonins: IgG and C3b</li>
    </ul>
    <li>Bacterium/foreign object engulfed by a phagosome</li>
    <li>
      Phagosome fuses with lysosome with &ldquo;respiratory burst&rdquo; of metabolic activity
      producing hydrogen peroxide
    </li>
    <ul>
      <li>Myeloperoxidase increases the effectiveness of hydrogen peroxide</li>
      <li>Lactoferrin inhibits microorganisms growth</li>
      <li>Oxygen-dependent free radical formation also kills bacteria</li>
    </ul>
  </ul>
</ul>

## Macrophages
<ul>
  <li>
    Within tissues monocytes enlarge, increase lysosome numbers, Golgi, ER&nbsp; development etc.
    Macrophage activation leads to:
  </li>
  <ul>
    <li>Increased phagocytic capacity</li>
    <li>
      Production of hydrolytic enzymes, pyrogen and interferon (blocks translation of viral mRNA)
    </li>
    <li>Stimulates fibroblast proliferation and further polymorph production</li>
    <li>Lymphocytes activating factor (IL-1) stimulates T helper cells</li>
  </ul>
  <li>Stimulated by C3b (also an opsonin)</li>
  <li>Capable of cell division</li>
  <li>Contribute to antigen presentation</li>
  <li>Can fuse to form multinucleated giant cells (increased phagocytic activity)</li>
  <li>
    Epithelioid cells within granulomas are derived from a single macrophage (increased secretory
    capacity)
  </li>
</ul>
<ClinicalCorrelate>
  <p>
    Granulomatous keratic precipitates (&ldquo;mutton-fat&rdquo; KPs) are composed of macrophages
    compared to non-granulomatous KPs which are mainly lymphocytes and PMLs.
  </p>
</ClinicalCorrelate>

## Complement system
<ul>
  <li>
    Involved in acute inflammation, phagocytosis, clotting, immune and hypersensitivity reactions
    (C3a and C5a are anaphylatoxins)
  </li>
  <li>Classical and alternative pathways are both stimulated by plasmin</li>
  <li>C3a and C5a increases vascular permeability as above</li>
  <ul>
    <li>C5a is 1000x more active</li>
  </ul>
  <li>
    C5b joins with C6, C7, C8 and C9 to form the membrane attack complex (MAC) which is capable of
    cell lysis
  </li>
</ul>

## Plasma cascade system
<ul>
  <li>
    Factor XII (Hageman factor) of the clotting cascade has a central role in activating 3 systems
    operating within plasma
  </li>
  <ul>
    <li>Kinin system (via prekallikrein) to produce potent vasodilators</li>
    <li>Clotting cascade (via stimulating factor XI)</li>
    <li>Complement system (via activating plasminogen to plasmin)</li>
  </ul>
  <li>All three have positive feedback loops to activate more Hageman factor</li>
</ul>

## Chronic inflammation
<ul>
  <li>Response to persistent pathogen/irritant</li>
  <li>Cellular response predominates: mixed proliferation and destruction</li>
  <li>Unique cellular organisations: granuloma</li>
  <ul>
    <li>Granulomas represent failure of acute neutrophils to clear the pathogen</li>
    <ul>
      <li>Derived from macrophages and their lineage</li>
    </ul>
    <li>Inner core of macrophages and epithelioid cells with increased secretory capacity</li>
    <li>
      Core surrounded by activated macrophages (containing ingested micro-oganisms) and T
      lymphocytes
    </li>
    <li>Outer layer of fibroblasts and multinucleated giant cells</li>
    <li>Caseation is a feature of tuberculous granulomas</li>
  </ul>
  <li>
    Granulomatous inflammation may be non-infectious: example of delayed hypersensitivity response
    (type IV)
  </li>
  <ul>
    <li>Response to breakdown of endogenous materials&nbsp;</li>
  </ul>
</ul>
<ClinicalCorrelate>
  <>
    <p>
      A chalazion is a type IV reaction to rupture of a blocked meibomian gland duct releasing
      irritant keratin.
    </p>
    <ul>
      <li>Response to exogenous non-biological materials ie. foreign body</li>
      <li>Mainly mycobacteria eg. TB or leprosy and fungi</li>
      <li>Unknown eg sarcoidosis (non-caseating)</li>
    </ul>
  </>
</ClinicalCorrelate>
<ul>
  <li>Non-granulomatous inflammation</li>
  <ul>
    <li>Characterised by lymphocytes and plasma cells</li>
    <li>Behcet&rsquo;s disease</li>
    <li>Multiple sclerosis</li>
  </ul>
</ul>

## Corneal angiogenesis
<ul>
  <li>Response to inflammation promoted by fibrin and its degradation products</li>
  <li>Latent period</li>
  <ul>
    <li>Vasodilation&nbsp;</li>
    <li>Vascular permeability of neighbouring vessels</li>
    <li>Stromal oedema</li>
  </ul>
  <li>Endothelial activation (within 24 hours)</li>
  <ul>
    <li>Endothelium retracts and nucleoli enlarge</li>
  </ul>
  <li>Endothelial basal lamina broken down by plasminogen activator</li>
  <ul>
    <li>Produced by fibroblasts, macrophages and others</li>
  </ul>
  <li>Vascular sprouting</li>
  <ul>
    <li>Sprouts from post-capillary venules and capillaries</li>
    <li>Lumen formation and anastomosis of blind channels</li>
  </ul>
  <li>Vascular maturation: deposition of ECM and laminin and basal lamina formation</li>
</ul>


Pathology

Inflammation

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Cornea

Corneal Structure And Development

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Collagen

Tissue Damage

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Free Radicals And Antioxidants

Immunology

Ocular Immunology

Microbiology

Viral Infections

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Antimicrobials

Genetics

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Chromosome Defects

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance