BI: After Midterm

Definition of inflammation

A host response to eliminate altered cells, foreign bodies, microorganisms, and antigens; characterized by movement of fluid and cells from blood into extravascular tissue

Who first described inflammation as a non-specific, beneficial response to injury?

John Hunter (18th century Scottish surgeon)

Three steps in the inflammatory response

Initiation, Amplification, Termination

Five vascular changes in acute inflammation

Vasodilation, increased blood flow, loss of endothelial integrity, leakage of fluid/proteins, emigration of WBCs

The cardinal signs of inflammation (Celsus)

Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain)

Who added the 5th cardinal sign, Functio Laesa?

Virchow

Who first microscopically described inflamed vessels in frog tissue?

Julius Cohnheim

Main cells of acute inflammation

Neutrophils

Main cells of chronic inflammation

Lymphocytes, macrophages, plasma cells, granulation tissue, fibrosis

Starling's forces regulate

Movement of fluid in and out of the vasculature (via hydrostatic pressure and colloid osmotic pressure)

Non-inflammatory edema occurs when

ECF formation exceeds lymphatic clearance (no increased vascular permeability)

Transudate

Low-protein ECF (specific gravity < 1.015)

Exudate

High-protein ECF (specific gravity > 1.015)

Protein content of pulmonary edema fluid in CHF

Low (transudate) — normal capillary permeability, just increased hydrostatic pressure

Protein content of pleural fluid in pneumonia

Elevated (exudate) — increased vascular permeability

Cause of edema in nephrotic syndrome/malnutrition

Decreased colloid osmotic pressure from low plasma protein

Cause of lymphedema

Obstruction of lymphatics (surgery, radiation, cancer, filariasis)

Who described the "triple response" of the skin?

Sir Thomas Lewis

Three phases of the triple response

White line (vasoconstriction) → Flare (vasodilation) → Wheal (leaky vessels, edema)

Two mechanisms of increased vascular permeability

Endothelial cell contraction (gap formation), direct endothelial injury

Serous exudate

Inflammatory exudate without a prominent cellular response

Fibrinous exudate

Inflammatory exudate with large amounts of fibrin

Purulent/suppurative exudate

Inflammatory exudate with liquefactive necrosis (pus)

Cells that release histamine and serotonin

Mast cells, basophils, and platelets

Trigger for mast cell degranulation

Antigen binding IgE on cell membrane, anaphylatoxins (C3a, C5a), physical stimuli (cold)

Four major plasma-derived mediator cascades

Complement, Coagulation, Kinin/kallikrein, Fibrinolytic system

Factor that activates all four plasma mediator systems

Factor XII (Hageman factor)

Complement anaphylatoxins that release histamine

C3a, C4a, C5a

Complement fragment that is chemotactic for neutrophils

C5a

Complement fragment that opsonizes bacteria

C3b

What does kallikrein do?

Converts kininogen to bradykinin; converts plasminogen to plasmin

Effect of bradykinin

Increases vascular permeability and causes pain

Effect of plasmin

Degrades fibrin (produces FSPs), activates complement (C3a to C3b)

Vasodilators secreted by endothelial cells

Prostacyclin (PGI2), Nitric oxide

Vasoconstrictor secreted by endothelial cells

Endothelin

Roles of nitric oxide in inflammation

Vascular smooth muscle relaxation, decreased platelet aggregation, decreased leukocyte recruitment, antimicrobial activity

Four steps of leukocyte recruitment

Margination, Adherence, Emigration, Chemotaxis

Chemotactic factors for neutrophils

C5a, bacterial peptides (fMLP), chemokines (IL-8), leukotriene B4, cytokines

Three steps of phagocytosis

Recognition (opsonization), Internalization, Digestion

Who discovered the macrophage and phagocytosis?

Ilya Mechnikoff (Nobel Prize 1908)

Oxygen-dependent bactericidal mechanisms

Superoxide, hydrogen peroxide, hypochlorous acid (via myeloperoxidase), hydroxyl radicals

Enzyme deficient in chronic granulomatous disease

NADPH oxidase

Oxygen-independent bactericidal mechanisms

Lysosomal hydrolases, defensins, lactoferrin, lysozyme, major basic protein

Clinical examples of leukocyte-induced tissue injury

ARDS, transplant rejection, glomerulonephritis, reperfusion injury, septic shock, vasculitis

Endogenous pyrogens causing fever

IL-1, TNF-alpha

Mechanism of fever

Increased prostaglandin synthesis in hypothalamus

"Shift to the left" refers to

Release of immature neutrophils into the blood

Components of the acute phase response

Fever, leukocytosis, anorexia, altered sleep, increased acute phase proteins

Where are acute phase proteins made, and what stimulates them?

Liver; stimulated by IL-6

Effect of acute phase proteins on ESR

Increases ESR (erythrocyte sedimentation rate)

Toll-like receptors (TLRs) recognize

PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns)

Best-characterized TLR and its ligand

TLR4, activated by LPS (endotoxin)

2011 Nobel Prize in Medicine was awarded for discovery of

Toll-like receptors (Hoffmann, Beutler, Steinman)

Six outcomes of resolved inflammation

Return to normal permeability, lymphatic drainage of fluid, macrophage pinocytosis of fluid, phagocytosis of apoptotic neutrophils, phagocytosis of debris, disposal of macrophages