Inflammation, Healing and Repair

Question 1

what are the 5 causes of inflammation?

Answer 1

physical
infective
chemical
immunological: hypersensitivity
other

Question 2

what kinds of physical inflammation are there?

Answer 2

trauma
heat/cold
radiation

Question 3

what kinds of infective inflammation are there?

Answer 3

bacteria
parasites
viruses

Question 4

what kinds of chemical inflammation are there?

Answer 4

simple poisons e.g. acid

organic poisons e.g. paraquat

Question 5

what kinds of immunological: hypersensitivity reactions are there?

Answer 5

antigen-antibody

cell-mediated

Question 6

what other kinds of inflammation are there?

Answer 6

vascular

hormonal

Question 7

what do calor, dolor, rubor and tumor stand for?

Answer 7

calor - pain
dolor - heat
rubor - redness
tumor - swelling

Question 8

what is congestion?

Answer 8

blood accumulates in organ or tissue as the result of decreased venous return

Question 9

what kind of process is congestion?

Answer 9

passive

Question 10

why does congestion occur?

Answer 10

increased central venous pressure or blockage/obstruction of venous return from a particular vascular bed

Question 11

how does congestion differ from hyperaemia?

Answer 11

congestion is pathological

hyperaemia is an active, physiological reaction to injury

Question 12

what kind of inflammation does congestion lead to?

Answer 12

predisposes to haemorrhaging -> inflammation -> causes fibrosis and organ dysfunction

Question 13

explain how hepatic congestion causes inflammation

Answer 13

1. increased central venous pressure in congestive heart failure
2. increased pressure in central veins
3. expansion
4. pressure on hepatocytes
5. disrupts function
6. cell death (centrilobular necrosis)
7. microhaemorrhages, fibrosis around central veins = permanent dysfunction

Question 14

explain how chronic lung congestion causes inflammation

Answer 14

1. chronic congestion in the lungs
2. microhaemorrhages
3. accumulation of haemosiderin-containing macrophages in alveoli and chronic inflammation and fibrosis in interstitial lung tissue
4. scarring
5. decreased lung compliance
6. impaired gas exchange

Question 15

what is indicative of cellular dysfunction resulting from abnormally increased central venous pressure in the liver?

Answer 15

Cytoplasmic vacuolisation of hepatocytes

Question 16

what 3 signs/symptoms are there of inflammation at a microscopic level?

Answer 16

Hyperaemia
Exudation of fluid
Emigration of leucocytes

Question 17

how does hyperaemia lead to vascular dilation?

Answer 17

injury causes a direct affect on vessels -> vascular dilation
injury causes a nervous reaction (axon-reflex) -> vascular dilation
injury damages cells which release chemical mediators which lead to vascular dilation

Question 18

what is the mechanism of exudation: fluid movement?

Answer 18

hyperaemia -> capillary blood pressure rises -> increased filtration pressure

loss of protein from capillaries -> reduced plasma osmotic pressure -> increased filtration pressure

interstitial tissue protein increase -> increased tissue osmotic pressure -> increased filtration pressure

……..

increased filtration pressure -> local swelling (oedema) -> increased lymph flow from area

Question 19

how does the net movement of plasma proteins and fluid moving into the interstitial space occur?

Answer 19

electrolytes in the artierial side and protein increase the oncotic pressure from osmotic conditions - the increased oncotic pressure moves water and protein out of the vessel from the venal side

Question 20

what is the advantage of exudation?

Answer 20

fluid increase -> dilution of toxins (reduce toxin concentration in the area)

Question 21

what is the contents of the exudation fluid?

Answer 21

• globulins (protective antibodies)
• fibrin deposition ( limit bacterial spread)
• various factors (promoting healing)

Question 22

what is the exudation protein passage?

Answer 22

chemical mediatiors:

• endothelial contraction
• increased permeability*

direct endothelial injury (e.g. burns) - increased permeability*

Question 23

which cell is the first to the site of damage?

Answer 23

neutrophil

Question 24

what do neutrophils do?

Answer 24

degrade cell debris (cells damaged from toxins etc)

Question 25

what kind of cells are neutrophils?

Answer 25

phagocytes

Question 26

where are neutrophils made?

Answer 26

bone marrow

Question 27

how long are neutrophils around for?

Answer 27

short lives - 1-3 days

Question 28

what enzymes do neutrophils contain and what do they do?

Answer 28

- myeloperoxidase (generates hydrogen peroxide) - lysozyme - acid hydrolase (hydrolysis)

Question 29

what kind of nucleus does a neutrophil have?

Answer 29

polymorphonuclear

Question 30

how do neutrophils kill?

Answer 30

1. engulf bacteria by opsonisation 2. endocytosed 3. endocytic vesicle 4. fuses with lysozymes 5. phagolysozome created 6. respiratory burst 7. oxygen free radicals from respiratory burst 8. contributes to hydrogen peroxide formation 9. hydrogen peroxide free radicals 10. all react with bacteria and kill it

Question 31

how do neutrophils do 'opsonisation'?

Answer 31

wrap bacteria in antibodies/c3 | antibodies/c3 receptors on neutrophil to engulf it

Question 32

how does having repeat bacterial infections affect neutrophils?

Answer 32

low opsonisation or low killing mechanisms

Question 33

what do eosinophil granules look like?

Answer 33

red/pink granules with H & E staining

Question 34

what events are eosinophils involved in?

Answer 34

type I hypersensitivity response

Question 35

what is the role of eosinophils?

Answer 35

damp down allergic hypersensitivity responses

Question 36

how do eosinophils reduce allergic responses?

Answer 36

produce histaminase, aryl sulphatase, phospholipase - degrade mast cell mediators

Question 37

what does histaminase do?

Answer 37

breakdown histamine made elsewhere

Question 38

what does phospholipase do?

Answer 38

degrade mast cell mediators

Question 39

what things do eosinophils kill?

Answer 39

antibody-coated parasites e.g. worms/flukes

Question 40

what events are mast cells involved in?

Answer 40

type I hypersensitivity mediated by IgE

Question 41

what do basophils and mast cells granules contain?

Answer 41

histamine, heparin, tryptase, acid hydrolase

Question 42

when do basophils and mast cells degranulate?

Answer 42

on activation

Question 43

what is the activated function of a basophil?

Answer 43

unknown

Question 44

what is the activated function of a mast cell?

Answer 44

release of granules

Question 45

what is the difference between monocytes and macrophages?

Answer 45

macrophages derive from monocytes

Question 46

what are macrophages?

Answer 46

major scavenger cells

Question 47

when do macrophages arrive?

Answer 47

12-24hrs after neutrophils

Question 48

what chemotactic factors do macrophages release?

Answer 48

TNF, PDGF, TGF-β

Question 49

what is the activated function of a macrophage?

Answer 49

phagocytosis and activation of bactericidal mechanisms , antigen presentation

Question 50

what events are macrophages involved in?

Answer 50

inflammatory and specific response

Question 51

where are macrophages found?

Answer 51

in the gut lining - checking for things

Question 52

how are B and T lymphocytes made?

Answer 52

small resting lymphocytes stimulated lymphoblasts formed effector B cell OR effector T cell produced

Question 53

what is the difference between acute and chronic inflammation?

Answer 53

acute - rapid onset, short duration | chronic - pathological consequences

Question 54

activated neutrophils have increased receptors for?

Answer 54

chemoattractants, prostaglandins, leukotrienes, Fc, complement, etc

Question 55

what is the difference in neutrophil production during inflammation?

Answer 55

Normally produce 1010/day, increases 10x

Question 56

why is metabolic activity stimulated during inflammation?

Answer 56

activation of neutrophils -> metabolic activity stimulated -> reactive oxygen and nitrogen intermediates and release of chemical mediators

Question 57

what is inflammation damage regulated by?

Answer 57

regulation of duration and intensity of inflammatory response - e.g. TGF-β

Question 58

what is the sequence of events of inflammation?

Answer 58

1. Bacteria enter tissues, cause damage 2. Mast cells release histamine, also prostaglandins and leukotrienes 3. Vasodilation of arterioles, increasing blood flow 4. Capillary permeability is increased, causing oedema, kininogens converted to kinins 5. Chemotaxis of neutrophils 6. Killing of bacteria 7. Tissue repair

Question 59

where are chemical mediators derived from?

Answer 59

Inflammatory cells | plasma

Question 60

what do mast cells release?

Answer 60

histamine

Question 61

what does histamine cause?

Answer 61

increased vascular permeability and vasodilation

Question 62

what does serotonin cause?

Answer 62

vasodilation

Question 63

what do prostaglandins cause?

Answer 63

vasodilation, oedema ( PGE2, PGI2)

Question 64

what leukotrienes cause?

Answer 64

vasoconstriction, increased permeability

Question 65

what do cytokines cause?

Answer 65

IL-2, IL-4 IL-10, TGF-β IFN-γ, TNF-α

Question 66

what do IL-2, IL-4 cause?

Answer 66

stimulate lymphocyte proliferation

Question 67

what do IL-10, TGF-β cause?

Answer 67

suppress lymphocyte proliferation

Question 68

what do IFN-γ, TNF-α cause?

Answer 68

macrophage activation

Question 69

what releases serotonin?

Answer 69

platelets

Question 70

what are prostaglandins and leukotrienes?

Answer 70

Arachadonic acid derivatives

Question 71

where are cytokines released from?

Answer 71

inflammatory cells, endothelium, etc

Question 72

what are the outcomes of inflammation?

Answer 72

- usually disappears in hours/days - tissue returns to normal - fluid and degraded protein drained by lymphatic system - exudate, debris and fibrin removed by phagocytes - inflammatory cells removed by apoptosis

Question 73

what must circulating neutrophils do to enter inflamed tissue?

Answer 73

adhere to and pass between endothelial cells Expression of cell-adhesion molecules (CAMs) is critical

Question 74

what are the 4 steps for neutrophil to enter the tissue?

Answer 74

1. rolling - low affinity binding of endothelial selectin molecules to neutrophil mucins 2. activation - endothelial cell activates integrin on the neutrophil -> firm binding 3. arrest/adhesion 4. migration - in response to chemoattractants