Chronic inflammation

Question 1

What is chronic inflammation compared to acute?

Answer 1

prolonged duration - wks/months - years
inflammatory cells = mononuclear- lymphocytes, plasma cells, macrophages
tissue destruction
healing involves angiogenesis and fibrosis

Question 2

How does acute inflammation progress to chronic inflammation?

Answer 2

repeated episodes e.g. peptic ulcer

persistence of injurious agents with failure of resolution e.g. osteomyelitis

Question 3

What are the different causes of primary chronic inflammation?

Answer 3

1) micro-organism associated with intracellular infection e.g. viral agents (hep B) or bacteria resistant to phagocytosis
2) Foreign body reactions - e.g. exogenous materials (silica, asbestos), endogenous substances (lipid material in atherosclerosis)
3) autoimmune diseases e.g. Hashimoto’s thyroiditis, RA
4) Unknown aetiology - chronic inflammatory bowel disease , sarcoidosis

Question 4

Give 2 examples of progression from acute inflammation to chronic due to repeated episodes

Answer 4

Chronic cholecystitis and chronic peptic ulceration

Both are associated with damage to deeper layers of the wall

• damaged smooth muscle cannot heal by regeneration
• healing by repair results in fibrous scarring- this affects contractility of tissue

Question 5

What predisposes acute inflammation of the gallbladder?

Answer 5

gallstones

Question 6

Why do peptic ulcers form?

Answer 6

imbalance between damaging and protective factors of the mucosa - too much HCl released and a lack of protective mucus - leads to flattening and loss of normal mucosal folds

Question 7

What are the consequences of chronic cholecystitis?

Answer 7

Gallbladder is non-contractile due to scar tissue, fatty food intolerance, RUQ pain

Question 8

What are the consequences of chronic peptic ulcers?

Answer 8

Fibrous scarring of stomach muscle which can lead to:

• pyloric stenosis = tend to suffer projective vomiting as stomach can’t process food
• gastric haemorrhage = fibrous tissue holds artery in place, preventing contraction

Question 9

What is the role of CD4+ T cells?

Answer 9

secrete cytokines in response to antigen presentation = activates CD8+ cells and macrophages
cooperate with B cells in humoral response

Question 10

What is the role of CD8+ T cells?

Answer 10

Effector cells

• direct cell killing by apoptosis
• produce cytotoxic cytokines

Question 11

What is the role of B cells?

Answer 11

Respond to stimulation by differentiating into plasma cells

Plasma cells secrete antibodies

Question 12

How can you distinguish plasma cells from lymphocytes?

Answer 12

Plasma cells have a much more abundant cytoplasm

Question 13

What are the key roles of resident macrophages e.g. kupffer cells?

Answer 13

phagocytosis and immune surveillance

Question 14

What happens to macrophages once they are activated by cytokines?

Answer 14

increase in size, mobility and phagocytic activity and produce a range of substances promoting tissue injury, angiogenesis and fibrosis

Question 15

When are macrophages commonly seen?

Answer 15

late stages of acute inflammation as they are involved in removing dead tissue and initiating tissue repair

Question 16

What effect does the production of toxic oxygen metabolites and arachidonic acid metabolites and proteases by macrophages have?

Answer 16

causes direct tissue damage

Question 17

What effect does the production of pro-inflammatory cytokines and chemokines by macrophages have?

Answer 17

activation and recruitment of other inflammatory cells

Question 18

What effect does the production of growth factors by macrophages have?

Answer 18

fibrosis and angiogenesis

Question 19

What effect does the production of collagenases by macrophages have?

Answer 19

remodelling of connective tissue

Question 20

What is a granuloma?

Answer 20

aggregate of macrophages

• may have epithelioid morphology
• little phagocytic activity once granulomas formed
• may fuse to form giant cells like langhan’s, foreign body and touton

Question 21

What are the causes of granulomatous disease (subtype of chronic inflammation)?

Answer 21

infections - mycobacteria (TB), syphilis
foreign bodies - endogenous (cholesterol crystals, necrotic bone), exogenous (silica, oils)
drugs - hepatic granulomas (sulphonamides)
unknown - CD, sarcoidosis, wegner’s granulamatosis

Question 22

What causes TB and what is the immune response?

Answer 22

mycobacterium TB

Mainly T cell mediated (delayed hypersensitivity), macrophages recruited with granuloma formation

Question 23

What occurs in the primary infection of the lungs in TB?

Answer 23

subpleural location (ghon focus), centre undergoes caseation necrosis (TNF-mediated) and bacilli are carried to regional lymph nodes (ghon complex)

Question 24

What is the sequelae of primary TB infection?

Answer 24

Heal by scarring, may undergo calification - CXR shows calcification
progressive pulmonary TB - local tissue destruction
Haematogenous spread - erosion of pulmonary vein or artery =miliary TB

If an inadequate immune response then the pathogen replicates- lung progressively gets destroyed= consumption

Question 25

What are the 2 types of miliary TB?

Answer 25

Pulmonary artery stenosis - lung infection

Pulmonary vein erosion - systemic infection - brain, liver, kidney = very high mortality

Question 26

What are the characteristic features of CD?

Answer 26

transmural (full thickness) of bowel wall
damage to smooth muscle heals by fibrosis - lose contractile component
stenosis may lead to bowel obstruction

Question 27

What are the characteristic features of UC?

Answer 27

Chronic inflammation with ulceration
mucosa heals by regeneration
repeated cycles of ulceration/regeneration
may progress to invasive carcinoma