Inflammation and repair

Question 0

Rubor in acute inflammation

+ Calor in acute inflammation

Answer 0

Redness - arteriole vasodilation (d/t histamine)

Heat - same as above

Question 1

Histamine function

Answer 1

Key chemical in acute inflammation
Mast cell release
Arteriole vasodilation
Incr venular permeability

Question 2

Tumor in acute inflammation

Answer 2

Swelling; incr vessel permeability

histamine

Question 3

Dolor in acute inflammation

Answer 3

Pain, bradykinin, PGE release

Question 4

Acute inflammation main cell mediators

Answer 4

Neutrophil dominant, Incr in IgM

Question 5

Initial vessel events in acute inflammation

Answer 5

Transient vasoconstriction –> arteriolar vasodilation –> incr venular permeability

Question 6

Neutrophil margination in acute inflammation:

Answer 6

Due to selectins
Integrins –> neutrophil adhesion molecules;

C5a and LTB4 activate –> neutrophil margination
CD11/CD18 - are markers for integrins

Question 7

Endothelial cell adhesion molecules are activated by:

Answer 7

Activated by IL1 and TNF

Question 8

ICAM

VCAM

Answer 8

Intercellular adhesion molecule

vascular cell adhesion molecule

Question 9

Leukocyte adhesion molecule defect

Answer 9

Failure of umbilical cord to separate

- poor wound healing

Question 10

Causes of Decr activation of neutrophil adhesion molecules

Causes of Incr activation of neutrophil adhesion molecules

Answer 10

Neutrophillic leukocytosis; corticosteroids

neutropenia; endotoxins

Question 11

Chemotaxis directed by

Answer 11

Movement directed by C5a and LTB4

Question 12

Opsonising agents

Answer 12

IgG, C3b –> enhance phagocytosis

Question 13

Neutrophils, monocytes, macrophages have receptors for:

Answer 13

IgG, C3b

Question 14

O2 dependent MPO system

Answer 14

Most potent microbicidal system –> in neutrophils and monocytes.

Produces superoxide from O2 via NADPH oxidase with NADPH cofactor; produces respiratory burst

Question 15

Test for respiratory burst:

Enzyme which converts superoxide to peroxide

Answer 15

Nitroblue tetrazolium (NBT)
Superoxide dysmutase

Question 16

Chronic granulomatous disease

Answer 16

Absent NADPH oxidase –> no respiratory burst
Staphylococcus aureus is NOT killed (catalase positive)
Streptococcus killed (catalase Negative)

Question 17

Genetic Microbicidal defects:

Answer 17

Chronic granulomatous disease of childhood (XR)

Myeloperoxidase deficiency (AR)

Question 18

Myeloperoxidase

Answer 18

Lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)

Question 19

Genetic Opsonisation defect:

Phagocytosis defect:

Answer 19

Bruton’s agammaglobulinaemia (XR, decr IgG)

Chediak-Higashi - Membrane protein defect in transfering lysosomal enzymes to phagocytic vacuoles. AR and giant lysosomes. also has defect in microtubule polymerisation

Question 20

Actions of Cytokines:

• PGE2
• PGI2
• NO
• IL1 and TNF
• IL6

Answer 20

• PGE2 - vasodilation, fever
• PGI2 - vasodilation, prevent platelet aggregation
• NO - vasodilator, FR gas from conversion of arginine to citrulline
• IL1 and TNF - fever, synthesis of acute phase reactants in liver, leukocytosis
• IL6 - stimulated by IL1, stimulates synthesis of APR

Question 21

Acute phase reactants:

Answer 21

Fibrinogen, ferritin, C-reactive protein

Question 22

Bradykinin function

Answer 22

Kinin produced in conversion of factor XII to factor XI

mediates pain, vasodilation;
incr vessel permeability,

Iatrogenic association: cough/angioedema ACE inhibitors.

Question 23

Anaphylatoxins

Answer 23

C3a and C5a. directly stimulate mast cell release of histamine

Question 24

Prostaglandin I1

Answer 24

Synthesised by endothelial cells Vasodilator Inhibits platelet aggregation

Question 25

Lipoxygenase pathway Which drug inhibits lipoxygenase? Which drugs block lipoxygenase receptor?

Answer 25

- hydroxylation of arachidonic acid pathway - Zileuton - Zafirlukast, montelukast

Question 26

Effect of LTC4, D4, E4

Answer 26

bronchoconstriction

Question 27

Thromboxane A2 function

Answer 27

Synthesised by platelets; Effects: platelet aggregation, vasoconstriction, bronchoconstriction

Question 28

Corticosteroid actions:

Answer 28

- inhibits phospholipase A2 - inhibits activation of neutrophil adhesion molecules - neutrophilic leukocytosis, lymphopenia, eosinopenia

Question 29

Fever effect on body

Answer 29

Right shift OBC | - hostile to bacterial/viral replication

Question 30

Pseudomembranous inflammation

Answer 30

Toxins from Corynebacterium diptheriae, clostridium difficile

Question 31

Cellulitis pathology

Answer 31

Subcutaneous inflammation | - strep pyogenes (hyaluronidase)

Question 32

Suppurative inflammation example:

Answer 32

Abscess formation | - staphylococcus aureus (coagulase)

Question 33

Chronic inflammation

Answer 33

Monocyte/macrophage mediated Incr IgG Repair by fibrosis

Question 34

Granuloma formation pathology

Answer 34

Cellular immunity; macrophages interact with Th1 cells - memory cells

Question 35

Collagen fibres function | - types of collagen

Answer 35

Triple helix of cross-linked alpha chains. Cross links at points of hydroxylation -- to increase tensile strength Type 1 collagen: bones, tendons Type 2: Cartilage Type 3: Early wound repair (everything else) Type 4: Basement membrane Type X: epiphyseal plate

Question 36

Cell cycle key checkpoint Action of TP53 and RB suppressor gene Action of BAX gene

Answer 36

Key checkpoint from G1 to S phase - arrests cell in G1 phase for DNA repair or apoptosis - stimulates apoptosis. Is activated by TP53 if too much DNA damage

Question 37

Extracellular matrix formed by: Complete restoration possible in cells which are: Scar tissue:

Answer 37

- Basement membrane, interstitial matrix - cell capable of duplication, no damage to basement membrane - end product of repair by connective tissue

Question 38

Define: Laminin Fibronectin Keloid

Answer 38

- Key basement membrane glycoprotein - Key interstitial matrix glycoprotein - Excessive type III collagen - common in blacks

Question 39

Angiogenesis in wound repair | Key events in wound repair

Answer 39

- basic fibroblast growth factor + vascular endothelial growth factor - Key event: Granulation tissue formation - fibronectin is responsible. BECOMES SCAR TISSUE

Question 40

% normal tensile strength of a healed wound

Answer 40

80

Question 41

Inhibition of wound healing (factors):

Answer 41

Infection (MCC S.aureus) Zinc deficiency DM

Question 42

Ehlers-Danlos syndrome

Answer 42

Defects in collagen synthesis and structure; hyperelasticity

Question 43

Scurvy

Answer 43

Decr collagen tensile strencth by decreasing cross-links at points of hydroxylation

Question 44

Pyogenic granuloma

Answer 44

Exuberant granulation tissue - bleeds when touched

Question 45

Healing by primary intention: Healing by secondary intention:

Answer 45

Clean wound --> appose wound margins with suture Infected wound - leave wound open --> myofibroblasts are important in healing defect

Question 46

HEALING in liver injury: - Lung injury - CNS injury

Answer 46

- regenerative nodules; abnormal cytoarchitecture - type II pneumocyte repair cell - astrocyte and microglial cell repairs cells --> gliosis

Question 47

WBC alterations in acute inflammation: Effects of ESR Function of CRP

Answer 47

Neutrophilic leukocytosis, left shifts the curve, toxic granulation - increased fibrinogen enhances rouleau - indicator of acute inflammation and inflammatory atheromatous plaque.

Question 48

Polyclonal gammopathy

Answer 48

Diffuse elevation of gamma-globulins - Incr IgG - chronic inflammation