Inflammation and Healing

Question 1

define inflammation

Answer 1

local tissue response to injury

Question 2

name some beneficial effects of inflammation

Answer 2

Destruction of invading microorganisms.

Walling off of an abscess cavity - preventing spread of infection.

Question 3

give examples of how inflammation may cause disease

Answer 3

An abscess in brain = space-occupying lesion, compressing surrounding structure.
Fibrosis from chronic inflammation - distort tissues, alter function.

Question 4

define acute inflammation

Answer 4

the initial and often transient series of tissue reactions to injury

Question 5

define chronic inflammation

Answer 5

subsequent and often prolonged tissue reactions following the initial response

Question 6

what type of cell is characteristically recruited in acute inflammation?

Answer 6

neutrophil polymorph

Question 7

list the possible outcomes of acute inflammation

Answer 7

suppuration (e.g. abscess)
organisation
progression to chronic inflammation
resolution

Question 8

what is the vascular component of acute inflammation?

Answer 8

dilatation of vessels

Question 9

what is the exudative component of acute inflammation?

Answer 9

vascular leakage of protein-rich fluid

Question 10

list the causes of acute inflammation

Answer 10

microbial infections;
hypersensitivity reactions;
physical agents;
chemicals;
bacterial toxins;
tissue necrosis (e.g. ischaemic infarction)

Question 11

name some physical agents that may cause acute inflammation

Answer 11

trauma; ionising radiation; heat; cold

Question 12

name some chemical agents that may cause acute inflammation

Answer 12

corrosives; acids; alkalis; reducing agents

Question 13

describe how a microbial infection causes acute inflammation

Answer 13

viruses - death of individual cells by intracellular multiplication.
bacteria - release of exotoxins/endotoxins

Question 14

how does a hypersensitivity reaction cause acute inflammation?

Answer 14

inappropriate/excessive immune reaction damages tissues

Question 15

define tissue necrosis

Answer 15

death of tissues from lack of oxygen/nutrients resulting from inadequate blood flow (infarction)

Question 16

what are the macroscopic appearances of acute inflammation?

Answer 16

redness - rubor
heat - calor
swelling - tumor
pain - dolor
loss of function

Question 17

what causes redness/rubor in acute inflammation?

Answer 17

dilatation of small blood vessels within the damaged area

Question 18

what causes the heat associated with inflammation of peripheral parts of the body?

Answer 18

increased blood flow (hyperaemia) through the region - vascular dilatation and delivery of warm blood

Question 19

what causes swelling associated with acute inflammation?

Answer 19

oedema - accumulation of fluid in extravascular space as part of fluid exudate.
also physical mass of inflammatory cells.

Question 20

what causes the pain associated with acute inflammation?

Answer 20

stretching/distortion of tissues due to oedema.
pus under pressure in an abscess cavity.
chemical mediators (bradykinin, prostaglandins, serotonin)

Question 21

what causes loss of function in acute inflammation?

Answer 21

movement of inflamed area is consciously and reflexly inhibited by pain.
severe swelling may limit movement.

Question 22

If there are neutrophil polymorph’s present, is it acute or chronic inflammation?

Answer 22

acute

Question 23

what are the three processes involved in acute inflammation?

Answer 23

1. changes in vessel calibre and flow
2. increased vascular permeability and formation of fluid exudate
3. formation of cellular exudate - migration of neutrophil polymorphs into extravascular space

Question 24

describe the changes in vessel calibre seen in acute inflammation

Answer 24

dilatation of arteriole
opening of pre-capillary sphincter
most capillaries full of blood

Question 25

give some examples of chemical mediators that increase vascular permeability in acute inflammation?

Answer 25

histamine bradykinin nitric oxide

Question 26

what is exudation?

Answer 26

net escape of protein-rich fluid from blood vessels

Question 27

what proteins are present in the fluid exudate seen in inflammation?

Answer 27

immunoglobulins | coagulation factors - fibrin deposition

Question 28

describe the process of neutrophil polymorph migration into tissues in acute inflammation

Answer 28

1. margination of neutrophils 2. pavementing of neutrophils 3. pass between endothelial cells 4. pass through basal lamina and migrate into adventitia

Question 29

what is the main source of histamine?

Answer 29

mast cells, stored in granules in their cytoplasm

Question 30

what stimulates histamine release?

Answer 30

C3a and C5a | lysosomal proteins released from neutrophils

Question 31

what is the effect of histamine?

Answer 31

dilates vessel | increases vascular permeability

Question 32

describe the role of tissue macrophages in acute inflammation

Answer 32

secrete chemical mediators that attract neutrophil polymorphs to the site

Question 33

describe the role of the lymphatics in acute inflammation

Answer 33

channels dilate, and drain away the oedema fluid, limiting swelling. antigens are carried to regional lymph nodes for recognition by lymphocytes.

Question 34

what is the major role of neutrophil polymorphs in acute inflammation?

Answer 34

PHAGOCYTOSIS

Question 35

describe the steps of phagocytosis

Answer 35

1. adhesion of particle to cell surface (opsonisation facilitates) 2. ingestion of particle by sending out pseudopodia 3. fusion of lysosomes with the phagosome - phagolysosome 4. intracellular killing of microorganism

Question 36

list the five terms used to describe special macroscopic appearances of acute inflammation - as dependent on the type of tissue involved and the type of agent provoking the inflammation.

Answer 36

``` serous suppurative (purulent) inflammation membranous inflammation pseudomembranous inflammation necrotising (gangrenous) inflammation ```

Question 37

describe some beneficial effects of acute inflammation

Answer 37

dilution of toxins - allows them to be carried away in lymphatic. entry of antibodies - phagocytosis, toxin neutralisation. transport of drugs (antibiotics) to inflamed area fibrin formation impedes movement of microorganisms.

Question 38

describe some harmful effects of acute inflammation

Answer 38

vascular damage. swelling - e.g. airway obstruction inappropriate inflammatory response - type 1 hypersensitivity reactions (e.g. hayfever)

Question 39

what factors determine the outcome of acute inflammation?

Answer 39

type of tissue involved. amount of tissue destruction. both of these depend on nature of injuring agent.

Question 40

what is the usual result of acute inflammation?

Answer 40

resolution

Question 41

what causes acute inflammation to progress to suppuration?

Answer 41

excessive exudate

Question 42

what causes acute inflammation to progress to organisation?

Answer 42

excessive necrosis

Question 43

what causes acute inflammation to progress to chronic inflammation?

Answer 43

persistent causal agent

Question 44

what conditions favour resolution of acute inflammation?

Answer 44

minimal cell death/tissue damage. occurred in organ with regenerative capacity (e.g. liver) rapid destruction of causal agent rapid removal of fluid/debris - good local vascular drainage.

Question 45

what is pus?

Answer 45

a mixture of living/dying/dead neutrophils and bacteria, cellular debris and possibly globules of lipid

Question 46

what conditions favour progression of acute inflammation to organisation?

Answer 46

large amounts of fibrin. lots of necrotic tissue. exudate and debris not removed/discharged

Question 47

what are the systemic effects of inflammation?

Answer 47

``` pyrexia. constitutional symptoms. weight loss. reactive hyperplasia of reticuloendothelial system. haematological changes. amyloidosis. ```

Question 48

what are the predominant cells seen in chronic inflammation?

Answer 48

lymphocytes, plasma cells and macrophages | also fibroblasts and multinucleate giant cells

Question 49

list the causes of chronic inflammation

Answer 49

primary chronic inflammation transplant rejection progression from acute inflammation recurrent episodes of acute inflammation

Question 50

give some examples of causes of primary chronic inflammation

Answer 50

TB, leprosy, viral infections - resistance to phagocytosis. endogenous - necrotic adipose tissue, bone exogenous - silica, asbestos, sutures, prostheses autoimmune diseases chronic IBD eg ulcerative colitis primary granulomatous diseases - Crohn's, sarcoidosis

Question 51

what are the macroscopic appearances of chronic inflammation?

Answer 51

``` chronic ulcer chronic abscess cavity thickening of wall of a hollow viscus granulomatous inflammation fibrosis ```

Question 52

describe the cellular infiltrate seen in chronic inflammation

Answer 52

lymphocytes, plasma cells and macrophages. possibly a few eosinophil polymorphs, but no neutrophil polymorphs. some macrophages may form neutrophil giant cells.

Question 53

describe the differences between macrophages and neutrophil polymorphs

Answer 53

macrophages can ingest a wider range of materials. neutrophil polymorphs last 3 days - destroy themself when they ingest microorganisms. Macrophages are long-lived - if they can't kill ingest microorganisms, they will harbour them.

Question 54

give some examples of organisms that can survive inside macrophages

Answer 54

mycobacteria - M tuberculosis and M leprae. | histoplasma capsulatum.

Question 55

what are macrophages derived from? what system does this make them part of?

Answer 55

blood monocytes. | mononclear phagocyte system aka reticuloendothelial system.

Question 56

define a granuloma

Answer 56

aggregation of epithelioid histiocytes

Question 57

what cell types does a granuloma contain?

Answer 57

epithelioid histiocytes | also possible - lymphocytes and histiocytic giant cells

Question 58

give some examples of granulomatous disease

Answer 58

Tuberculosis leprosy Crohn's disease sarcoidosis

Question 59

describe the morphology of an epithelioid histiocyte

Answer 59

``` vague histological resemblance to epithelial cells. large vesicular nuclei eosinophilic cytoplasm. elongated. arranged in clusters. ```

Question 60

name a major secretory product of epithelioid histiocytes

Answer 60

angiotensin-converting enzyme | can use ACE levels as a marker for systemic granulomatous disease (e.g. sarcoidosis)

Question 61

what does association of granulomas with eosinophils indicate?

Answer 61

parasitic infection (e.g. worms)

Question 62

What type of granuloma is seen in TB?

Answer 62

granuloma with caseating necrosis

Question 63

what type of cells make multinucleate giant cells in granuloma?

Answer 63

histiocytes

Question 64

list some common causes of granuloma

Answer 64

TB, leprosy, fungi, parasites, syphilis. materials that resist ingestion - keratin, necrotic bone, talk, silica. beryllium Crohn's disease; sarcoidosis; Wegener's granulomatosis

Question 65

what causes formation of histiocytic giant cells?

Answer 65

accumulation of matter that is indigestible by macrophages. | especially when foreign particles are too large to be ingested by a single macrophage.

Question 66

describe the appearance of Langhans giant cells

Answer 66

horseshoe arrangement of peripheral nuclei at one pole of the cell - characteristic in TB

Question 67

what type of giant cell is characteristic in TB

Answer 67

Langhans giant cell

Question 68

describe the appearance of foreign body giant cells

Answer 68

large cells with nuclei randomly scattered throughout cytoplasm

Question 69

what must be present for there to be a granuloma?

Answer 69

EPITHELIOID HISTIOCYTES - giant cells are commonly seen in granulomas, but without epithelioid histiocytes, it's not a granuloma

Question 70

describe the appearance of Touton giant cells

Answer 70

central ring of nuclei, peripheral to which there is lipid material

Question 71

list some of the roles of chronic inflammation in systemic/organ-specific diseases

Answer 71

myocardial fibrosis after MI. initiation and propagation, and progression, of cancer e.g. ulcerative colitis, tissue response to asbestos fibres. atheroma development. tissue injury associated with neurodegenerative disorders e.g. MS

Question 72

differentiate between resolution and repair

Answer 72

Resolution - initiating factor removed, tissue undamaged/able to regenerate. Repair - initiating factor still present, tissue damaged and unable to regenerate.

Question 73

define repair

Answer 73

replacement of damaged tissue by fibrous tissue. | collagen is produced by fibroblasts.

Question 74

list types of cell that regnerate

Answer 74

``` hepatocytes pneumocytes all blood cells gut epithelium skin epithelium osteocytes ```

Question 75

what cell types don't regenerate?

Answer 75

myocardial cells | neurones

Question 76

describe the appearance of coagulative necrosis

Answer 76

firm, pale area with ghost outlines on microscopy

Question 77

describe the appearance of colliquative necrosis. where is this seen?

Answer 77

dead area is liquefied. | seen in the brain.

Question 78

what disease shows caseous necrosis? what is the appearance of this?

Answer 78

TB. | pale yellow semi-solid material.

Question 79

define gangrene, and its appearance

Answer 79

necrosis with putrefaction. follows vascular occlusion or certain infections. black.

Question 80

what is fibrinoid necrosis?

Answer 80

a microscopic feature in arterioles in malignant hypertension

Question 81

list the types of necrosis

Answer 81

``` coagulative colliquative caseous gangrene fibrinoid fat necrosis ```

Question 82

what causes fat necrosis?

Answer 82

trauma. | pancreatitis.

Question 83

give an example and explanation of complete restitution

Answer 83

complete restoration following loss of part of a regenerative cell population - e.g. healing of a minor skin abrasion.

Question 84

define organisation of tissues

Answer 84

repair of specialised tissues by formation of fibrous scar.

Question 85

how does organisation occur?

Answer 85

production of granulation tissue, laid on a scaffold of fibrin, and removal of dead tissue by phagocytosis.

Question 86

describe the formation of granulation tissue

Answer 86

capillary endothelial cells grow and proliferate into damaged area - open into vascular channels, arranged as loops. fibroblasts divide, secrete collagen/matrix, and acquire bundles of muscle fibres - myofibroblasts, function as SMCs. contract to reduce wound size.

Question 87

what does granulation tissue consist of?

Answer 87

loops of capillaries supported by myofibroblasts. | possible inflammatory cells.

Question 88

what causes wound contraction? what is its purpose?

Answer 88

contraction of myofibroblasts in granulation tissue. collagen is secreted, forming a scar. reduces volume of tissue for repair - but this produces a scar

Question 89

describe "healing by first intention"

Answer 89

apposed wound margins are joined by fibrin deposition, which is then replaced by collagen and covered by epidermal growth

Question 90

describe "healing by second intention"

Answer 90

wound margins are unapposed due to extensive tissue damage. tissue defect fills with granulation tissue. epithelial regeneration to cover surface. granulation tissue contracts - scar formation

Question 91

list some complications of scarring/wound contraction

Answer 91

stenosis (narrowing) - if tissue damage goes around the lumen of a tube obstruction of a tube due a stricture permanent shortening of a muscle - contracture burns can result in a lot of contraction - cosmetic damage, impaired motility

Question 92

describe abscess formation

Answer 92

1. pus accumulates in a tissue 2. becomes surrounded by a 'pyogenic membrane' 3. this consists of sprouting capillaries, neutrophils and occasional fibroblasts 4. this will eventually result in granulation and scarring

Question 93

what challenge does an abscess present for treating bacterial infection?

Answer 93

bacteria within abscess cavity are relatively inaccessible to antibodies and antibiotic drugs

Question 94

describe the difference between a bacterial endotoxin and an exotoxin

Answer 94

``` exotoxin = synthesised inside the cell endotoxin = associated with cell wall ```