FINAL REVIEW part 1 - Inflammation

Question 1

Ways cells adapt to stress?

Answer 1

1-Atrophy
2-Hypertrophy
3-Hyperplasia: more cells
4-Metaplasia: changing types (eg. mucocilliary)
5-Dysplasia: Cells are diff. sizes, nuclei diff, divide more rapidly. Prelude to cancer.
6-Anaplasia: cancer

Question 2

hypoxemia vs hypoxia vs ischemia vs anemia vs anoxia

Answer 2

1- lack O2 in arterial blood
2- Lack O2 in tissues
3 - Restriction in blood supply to tissue
4- Decrease in total amount of Hb in blood
5- Complete deprivation of O2 in tissue

Question 3

Mechanisms of cell injury (6)?

Answer 3

1- Depletion ATP
2- Influx Calcium
3- Mitochondrial damage and dysfunction
4- Accumulation of ROS
5- Defect in membrane permeability
6-Damage DNA/p+

Question 4

Hypoxic injury steps?

Answer 4

decrease O2 -> decrease oxidative phosphorylation of mitochondria -> reduce ATP prod. -> Na/K pump not working properly -> increase intracellular Na -> increase attraction of H2O intracellular -> increase cellular swelling -> Ribosome on ER detach due to swelling -> impaired p+ synthesis

also: reduce ATP prod. -> anaerobic glycolysis -> increase lactic acid -> decrease pH

Also: Reduce ATP -> release of Ca2+ from ER/mitochondria stores + Ca2+ (atp dependant) pump not working -> increase intracell. Ca2+ -> Activation of Enz. -> results in: membrane damage and nuclear damage

Question 5

Reactive oxygen species cause cell injury by three main reactions?

Answer 5

• Lipid peroxidation of membranes. Double bonds in membrane polyunsaturated lipids
• Cross-linking and other changes in proteins.
• DNA damage.

Question 6

Types of necrosis?

Answer 6

Coagulative: cell retain barriers
Liquefactive: Full neutrophiles, result in hole in tissues, absec
Caseous: caog + liqu necrosis, cheese like. In tuberculosis
Gangrene: Ischemic necrosis followed by bacterial attack

Question 7

Apoptosis characteristics?

Answer 7

1-requires active RNA/p+ synthesis
2-Cell quickly replaced
3-No inflammation

Question 8

Necrosis characteristics?

Answer 8

• Cell and organelles swell
• Membrane blebs
  last longer than apoptosis
• Followed by inflammation

Question 9

Apoptosis execution in two pathways?

Answer 9

1- Intrinsic - mitochondria: Lack growth factors/DNA damage/misfolded proteins -> Bcl-2 family sensors activation -> activation of effectors Bax and Bak -> These dimerize and create passage in mitochondria which allows for leakage of cytochrome C + cofactors -> Initiator caspases -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis
2- Extrinsic - 2.1Death receptors: Fas ligand (for Fas) ->Activation of death molecules on cell surface (mainly part of Tumor Necrosis Factor receptor family with a death domain inside the cell) Fas with a death domain -> Fas trimerize -> Creating the FADD (Fas Activating Death Domain) with 3 death domain inside the membrane -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis
2.2: TNF binds to TNF receptor 1 (TNFRI) -> Creating the TRADD -> FADD -> Activation of caspase cascade -> Executioner caspases -> Breakdown of cytoskeleton/endonucleases activation -> cytoplasmic blebs -> apoptotic body with ligands for phagocytic cell receptors -> Phagocytosis

Question 10

Acute inflam. steps?

Answer 10

1- Recognition of microbe, necrotic cells and foreign substances
2-Vascular changes: INcreased blood flow due to vasodilatation + increase vascular permeability
3-Leukocyte Recruitment :
4- Leukocyte Activation

Question 11

Transudate vs exsudate

Answer 11

Almost no p+, few blood cells

high p+, and lots blood cells

Question 12

3. Leukocytes recruitment steps?

Answer 12

3. 1. Margination and rolling: Margination = when WBC accumulate near periphery of vessels. Weak/transient interaction between leuko. and endothelial cells = mediated by SELECTINS (found on both). Expressed on endothelial by stimulation of histamine and thrombin
4. 2 Adhesion: Binding of INTEGRINS (on both WBC and endo. cells) causes firm adhesion
5. 3 Transmigration: Neutro. go between cells, then secrete COLLAGENASES to breakdown the basement membrane.
6. 4 Chemotaxis: Leuko. follow gradient of [].

Question 13

Phagocytosis stages

Answer 13

1. Recognition and attachment: TLR, Fc portion of IgG
2. Engulfment: Membrane zip up around microbe. This becomes a phagosome inside the cytosol. Lysosome (with ROS and Enz.) fuse to the phagosome, becoming a phagolysosome
3. Killing and Digestion

Question 14

Two major sources of inflammatory mediators?

Answer 14

1- Cell derived: Either preformed stocked in granules and secreted or de novo produced
2-Plasma p+-derived: Major source is the liver (Complement, Kinins, clotting system)

Question 15

Activation of complement system (3 pathways)?

Answer 15

• Classical : 2IgG activating C1
• Alternative: ON its own
• Lectin:

Question 16

All three pathways of complement activation leads to?

Answer 16

1. Activation of C3 => Formation of C3 convertase that cleave C3 to C3a and C3b
2. CHEMOTAXIS: C5a and C3a: Recruitment and activation of leuko. (also increase adhesion to endothelium)
3. OPSONIZATION: C3b bound on bacteria attracts phagocytes.
4. VASODILATATION: C3a and C5a
5. LYSIS: C5b to C9 create the membrane attack complex (MAC) that put a hole on B membrane.

Question 17

Kinin system activation leads to?

Role?

Answer 17

Bradykinin

a) Bind to GCPR on nociceptor causing pain and
b) increase vascular permeability, arteriolar dilation

Question 18

Prostanglandins formation and actions?

Answer 18

Phospholilase A-2 (Enz.) that liberates Arachidonic acid from membrane ->Cyclooxygenase (COX1 and 2) type 2 more involved in inflam. -> Prostaglandin
Functions: Vasodilation and increase vascular permeability and causes pain

Question 19

Chemokines receptor family?

Answer 19

CXCR and CCR

Question 20

Nitric oxide action?

Answer 20

Relaxation of smooth musc.

Question 21

Plt activating factors actions?

Answer 21

Vascular permeability, vasoconstriction, growth factors, clotting, chemotaxis.

Question 22

Systemic effects of inflammation (3) with cause?

Answer 22

1-Fever: Due to prostaglandins, reason b/c leukocytes speed increases
2-Leukocytis: Increase prod. in bone marrow
3-Acute phase response by liver: Increase mediators prod. Eg. C-Reactive p+ ->Opsonin, chemotactic

Question 23

What is Wallerian degeneration?

Answer 23

Regeneration of myelinated axons by Schwann cells (periphery) (they normally myelinate axons) guidance.

Question 24

Different intention repairs?

Answer 24

Primary: surgical with suture
Secondary: Large wound ->granulation tissue->large scare

Question 25

Fibroblast role?

Answer 25

• Lay down collagen for formation of Extra-Cellular Matrix (ECM)
• transform into myofibroblast and are contractile