MI25 - Cellular Adaptation, Inflammation, Repair Part 3

Biomedical Sciences IV

What are chemical mediators of inflammation?

Chemicals that cause acute and chronic inflammation.

What are the four major categories of chemical mediators of inflammation?

Vasoactive amines, plasma proteases, arachidonic acid metabolites, and cytokines.

What is the principal mediator of the immediate inflammatory response?

Histamine.

What vascular effects does histamine cause?

Dilation of arterioles and increased vascular permeability.

Where is histamine found?

Mast cells, basophils, and platelets.

What triggers histamine release?

Trauma, immune complexes, complement, and WBC lysosomal proteins.

Where is serotonin stored?

In platelets.

When is serotonin released?

When platelets aggregate.

What is the vascular effect of serotonin?

Causes vasoconstriction.

What is the primary mediator in the kinin system?

Bradykinin.

What are the actions of bradykinin?

Arteriolar dilation, increased venular permeability (causing erythema), and increased smooth muscle contraction.

Does bradykinin act quickly or slowly compared to histamine?

Acts slower.

What is the complement system?

A cascade of proteins aiding immune defense against microorganisms.

What activates the classical complement pathway?

Antigen–antibody complexes.

What activates the alternative complement pathway?

Bacterial endotoxins.

Which complement components act as anaphylotoxins?

C3a and C5a.

What do C3a and C5a cause?

Histamine release → vasodilation and increased vascular permeability.

Which complement component is a powerful chemotactic factor for PMNs?

C5a.

What complement components in combination also create chemotactic activity?

The C5b-6-7 complex.

What complement component acts as an opsonin?

C3b.

What does C3b do?

Coats bacterial walls to promote PMN/macrophage phagocytosis.

What components form the membrane attack complex (MAC)?

C5–C9.

What does the membrane attack complex do?

Inserts into cell membranes, allowing water/electrolytes to enter → cell lysis.

What inflammatory peptides are produced during fibrinogen activation?

Fibrinopeptides.

What do fibrinopeptides cause?

Increased vascular permeability and WBC chemotaxis.

How are arachidonic acid metabolites released from cells?

By phospholipases.

What inhibits phospholipase activity?

Steroids.

What two pathways metabolize arachidonic acid?

Cyclooxygenase and lipoxygenase pathways.

What does the cyclooxygenase pathway produce?

Prostaglandins and thromboxane.

What do prostaglandins cause?

Vasodilation, edema, and pain.

What does thromboxane cause?

Vasoconstriction and increased platelet aggregation.

What drugs inhibit prostaglandin and thromboxane formation?

NSAIDs and aspirin.

Why does aspirin lead to prolonged bleeding?

It irreversibly inhibits platelet thromboxane production.

What does the lipoxygenase pathway produce?

Leukotrienes.

What do leukotrienes cause?

Chemotaxis, neutrophil aggregation, vasoconstriction, bronchospasm, and increased vascular permeability.

Why can aspirin trigger asthma?

Blocking cyclooxygenase shunts arachidonic acid to the leukotriene pathway → bronchospasm.

What are cytokines?

Polypeptide messengers important in cellular immunity.

Which cytokines cause fever in acute inflammation?

IL-1 and TNF.

What cytokine stimulates C-reactive protein (CRP)?

IL-6.

What cytokines are potent PMN chemoattractants?

IL-8 and TNF.

What does CRP bind to?

Phosphocholine on damaged cell walls and microbes.

What is the function of CRP?

Acts like an opsonin, marking targets for phagocytosis.

Which complement protein does CRP bind to initiate the classical complement pathway?

C1.

What immune cells does CRP bind to?

Neutrophils and monocytes.

What does CRP binding stimulate?

Production of inflammatory cytokines.

What are the three possible outcomes of acute inflammation?

Resolution, progression to chronic inflammation, or connective tissue substitution (scarring).

What is resolution?

Healing by regeneration of parenchyma.

What tissues most readily regenerate?

Labile tissues.

What are examples of labile tissues?

Limbal stem cells (cornea), skin, gut, hematopoietic tissue.

What are stable tissues?

Tissues that normally do not divide but can proliferate with the right stimulus.

Examples of stable tissues?

Glands (e.g., salivary), liver, kidney, most connective tissues.

When does chronic inflammation occur?

When the inflammatory stimulus persists over time.

What replaces acute inflammatory cells in chronic inflammation?

Chronic inflammatory cells.

Common examples of chronic inflammation?

Apices of teeth with necrotic pulps, periodontitis, autoimmune diseases.

What cell types dominate chronic inflammation?

Lymphocytes, plasma cells, macrophages, and sometimes eosinophils.

How long does chronic inflammation last?

Months to years.

What causes chronic inflammation?

Failure to eliminate the acute agent, low-grade pathogens, autoimmune disease.

What cells replace neutrophils in chronic inflammation?

Lymphocytes, plasma cells, macrophages.

What do cytokines and growth factors stimulate during chronic inflammation?

Accumulation of WBCs, endothelial cells, and fibroblasts → granulation tissue formation.

What is granulation tissue composed of?

Edematous fibrous connective tissue, numerous endothelial cells (leaky capillaries), and chronic inflammatory cells.

What ocular lesion represents granulation tissue?

Pyogenic granuloma on conjunctiva or eyelid after surgery or hordeolum.

What characterizes granulomatous inflammation?

Granulomas made of macrophages, multinucleated giant cells, and surrounding lymphocytes.

What is the prototypical granulomatous disease?

Tuberculosis.

Is granulomatous inflammation the same as granulation tissue?

No — they are completely different processes.

What happens during late chronic inflammation?

Fibrous tissue begins to proliferate.

What is fibrosis?

Replacement of normal tissue with fibrous tissue.

In which tissues does fibrosis always occur?

Permanent tissues.

What are examples of permanent tissues?

Skeletal muscle, cardiac muscle, neurons.

Example of fibrosis after injury?

Myocardial infarction → fibrous scar (no muscle regeneration).

Example of permanent tissue disease?

Poliomyelitis → neurons destroyed → fibrosis → muscle atrophy.

What replaces granulation tissue during scar formation?

Fibrosis.

What do myofibroblasts do in healing?

Pull the wound edges together.

What collagen type appears in mature scars?

Type I collagen.

What happens to capillaries in scar formation?

They collapse as tissue becomes pale and firm.

What causes hemostasis after injury?

Platelet accumulation and fibrin formation.

What holds platelets together in a clot?

Fibrin and fibronectin.

Where does a fibrin scab form?

Only on skin.

Which cells phagocytose debris first?

Neutrophils.

Which cells follow neutrophils?

Macrophages.

What do platelets release to stimulate healing?

Platelet-derived growth factors.

What major process forms new blood vessels?

Angiogenesis.

When does granulation tissue appear?

About 2–5 days after injury.

Which cells cause wound contraction?

Myofibroblasts.

In which wounds is contraction most prominent?

Large wounds (can cause deformity).

What collagen type appears first?

Type III collagen (weeks 1–3).

What collagen replaces type III?

Type I collagen.

What happens to excess cells?

They undergo apoptosis.

Where do keratinocytes migrate from?

Edges of the wound.

Do keratinocytes migrate over or under the scab?

Under the scab.

When does the scab fall off?

When epithelialization is complete.

What is healing by primary intention?

Healing of closely apposed surfaces (e.g., sutured or knife wounds) → narrow scar.

What is healing by secondary intention?

Healing of an open wound → more obvious scarring.

What is an ophthalmic example of secondary intention healing?

Open eyelid wounds after tumor excision healing from the base outward.

What is a keloid?

Excessive, exuberant scar tissue extending beyond wound boundaries.

Who is more prone to keloids?

Dark-skinned individuals (15× more likely).

What mutation is found in keloids?

p53 mutation.

Can keloids occur after blepharoplasty?

Yes.

What are local factors in poor wound healing?

Foreign material, radiation therapy, wound location.

What are systemic factors in poor wound healing?

Malnutrition, steroids, diabetes mellitus.