MoD session 3: chronic inflammation

Question 1

Define chronic inflammation

Answer 1

A chronic response to injury with associated fibrosis. Overlaps with host immunity, can last years

Question 2

Characteristics of chronic inflammation?

Answer 2

Swelling
Pain
Fibrosis

Question 3

In what situations could chronic inflammation arise?

Answer 3

1. AI damage too severe to be resolved in a few days so takes over, e.g. in burn infections most common
2. Begins without AI: in chronic infections (e.g. TB), autoimmune conditions (e.g. rheumatoid arthritis) or chronic low-level irritation (e.g. reaction to foreign material)
3. Develops alongside AI, e.g. prolonged exposure to toxic agents

Question 4

Role of macrophages in CI?

Answer 4

Monocytes in blood, enter tissue become macrophages. Main cell type in CI, can replicate (unlike neutrophils), take over from neutrophils

Functions:

• phagocytosis
• secretion of cytokines
• synthesise complement components and clotting factors
• present antigen to immune system
• stimulate angiogensis
• induce fibrosis
• induce fever, acute phase reaction and cachexia

Question 5

How do macrophages/monocytes appear microscopically?

Answer 5

Similar to lymphocytes
Largest WBC
Kidney bean-shaped nucleus
Larger amount of cytoplasm compared to nucleus than lymphocytes
“Ground glass” appearance of granules. Not granulocytes

Question 6

Role of lymphocytes in CI?

Answer 6

If present, the areas without lymphocytes usually indicate some antigenic material is there.
Functions:
-processing antigens
-B lymphocytes–>plasma cells that secrete antibodies
-secrete cytokines
-natural cytotoxic killer cells kill cells
-T lymphocytes control some cytotoxic functions

Question 7

Microscopic appearance of lymphocytes?

Answer 7

Vary
Usually plasma cells have a clock-face nucleus: clumps of chromatin at periphery of nucleus, often an eccentric pink cytoplasm with lots of ER

Question 8

Role of eosinophils in CI?

Answer 8

Normally present but concentration increases in CI
Function:
-attack large parasites, e.g. worms
-allergic reactions and immune response (IgE relation)
-in some tumours e.g. Hodgkin’s lymphoma

Question 9

Microscopic appearance of eosinophils?

Answer 9

“Tomato wearing sunglasses”
Granules in cytoplasm stain bright red as acidophilic
Bilobed nucleus

Question 10

Which inflammatory cells are granulocytes?

Answer 10

Neutrophils
Eosinophils
Basophils (very blue staining granules)

Question 11

Role of fibroblasts and myofibroblasts in CI?

Answer 11

Fibroblasts respond to chemotactic stimuli and move to sites needed, where they produce collagen, elastin and GAGs.
Can differentiate into myofibroblasts which can contract to help healing

Question 12

How are giant cells formed?

Answer 12

Macrophages can fuse with each other due to the presence of foreign bodies or bacteria which cause frustrated phagocytosis

Question 13

Langhans type giant cell?

Answer 13

Horseshoe of nuclei around periphery, foamy cytoplasm

E.g. in TB

Question 14

Foreign body type giant cell?

Answer 14

Nuclei arranged randomly

Often when hard to digest the foreign body: giant cell sticks to its surface

Question 15

Touton’s type giant cell?

Answer 15

Nuclei in a ring towards centre, form in lesions with a high lipid concentration, and lesions will also contain foam cells (macrophages with foamy cytoplasm)
E.g. fat necrosis, xanthomas

Question 16

What are some complications of CI?

Answer 16

1. Fibrosis: fibroblasts stimulated by cytokines, excess collagen deposition, impairs organ function, if has myofibroblasts can contract and cause more problems (e.g. contraction of cirrhotic liver will impair portal blood flow, causing ascites)
2. Impaired function: e.g. chronic inflammatory bowel disease
3. Atrophy: loss of functional tissues. E.g. gastric mucosa loss causes increased lamina propria and lymphocytes
4. Inappropriate immune response: can attack innoculous targets or the body’s normal tissues.

Question 17

What is a granuloma?

Answer 17

A mass of macrophages that often form giant cells; the result of a particle that is poorly soluble or difficult to eliminate: a foreign body (e.g. a thorn) or “tough” bacteria (e.g. mycobacterium tuberculosis). Usually 0.5-1mm diameter. Also in leprosy and syphilis
Granuloma forms around the free or phagocytosed particle, or for unknown reason such as in Crohn’s disease

Question 18

Foreign body granuloma?

Answer 18

Contains macrophages and foreign body giant cells, epithelioid cells, fibroblasts at the periphery
Few or no lymphocytes
Develop around non-antigenic material such as surgical thread

Question 19

Hypersensitivity/immune granuloma?

Answer 19

Contain macrophages, giant cells (Langhans), more epithelioid cells than in FBG, some fibroblasts at periphery, lymphocytes
Develop around insoluble antigenic particles that cause cell-mediated immunity, can be harmful as occupy parenchymal space within organ
Can undergo central necrosis (e.g. in TB)

Question 20

Sarcoidosis?

Answer 20

Non-caseous granulomas form throughout the body, especially in the lymph nodes and lungs
Often affects young adult women, idiopathic

Question 21

Chronic cholecystitis?

Answer 21

Inflammation and ulceration of the gallbladder mucosa
Causes gall stones, fibrotic wall, repeat attacks of AI
If untreated CI will persist due to repeated obstruction by gallstones

Question 22

Gastritis?

Answer 22

Acute-alcohol, drugs
Chronic-helicobacter pylori

Both can cause CI and ulceration due to imbalance of acid production and loss of mucosal defence

Question 23

Inflammatory bowel disease?

Answer 23

Idiopathic, describes CD and UC.

• Crohn’s disease: transmural. Causes strictures, fistulae, and patchy full-thickness inflammation throughout the bowel. Can affect entire digestive system: from mouth to anus. Symptoms commonly include diarrhoea, abdo pain, fatigue, weight loss, blood in faeces
• Ulcerative colitis: superficial, only affects colon. Causes diarrhoea, abdo pain.

Question 24

Cirrhosis?

Answer 24

Common causes: alcohol, infection (HBC, HCV), immunological diseases, fatty liver, drug abuse
Causes fibrosis and impaired function

Question 25

Rheumatoid arthritis?

Answer 25

Autoimmune condition:
-localised effects- CI joint destruction
-systemic effects-can cause amyloidoses in organs
CI can stimulate immune response as well as CI causing pathology itself

Question 26

Wegeners granulomatosis?

Answer 26

Unknown cause but causes granulomas
Now called Granulomatosis with Polyangiitis
Commonly affects kidneys and lungs

Question 27

Tuberculosis-how bacteria cause disease and possible outcomes

Answer 27

Bacteria produce no toxins or lytic enzymes, but cause disease by persistence and induction of cell-mediated immunity. Tends to have granulomas with necrosis (caseous)
Outcomes:
1. Arrest, fibrosis, scarring
2. Erosion into bronchus: bronchopneumonia, TB in gastrointestinal tract
3. TB empyema (TB in pleura)
4. Erosion into blood stream –> miliary TB (TB in multiple organs)

Question 28

Features of Crohn’s disease?

Answer 28

Discontinuous distribution
Affects any part of the GI system
Classically a “cobbelstone” appearance to bowel mucosa
Granulomas often present
Common-anal lesions and bowel fistulae (as deeper inflammation)

Question 29

Features of ulcerative colitis?

Answer 29

Inflammation only in mucosa and submucosa
Commonly has crypt abscesses and distorted crypt architecture
Significant increased risk of colon cancer
Often most severe in distal colon
Colectomy often indicated
May develop complications in other organs e.g. bile ducts (Sclerosing cholangitis), liver (cirrhosis), spine (ankylosing spondylitis), skin ulcers, arthritis

Question 30

Microscopic features of rheumatoid arthritis?

Answer 30

Pus in joints
Hypertrophy
Immune cells
Damaged articular cartilage

Question 31

Define ulcer

Answer 31

A break in the skin or mucous membrane with loss of surface tissue, disintegration and necrosis of epithelial tissue

Question 32

How does H. pylori cause gastritis and what are the microscopic features?

Answer 32

Colonises gastric pits in mucosa, damages epithelial cells by release of enzymes, imbalance of acid leads to loss of mucosal defence so inflammation results

Microscopically: loss of mucous membrane, lamina propria has lymphocytes, plasma cells and neutrophils

Question 33

Describe what happens when a person inhales M. tuberculosis

Answer 33

1. AI-vascular dilation, exudate leaks into tissues
2. Neutrophils emigrate and begin phagocytosis
3. CI after a few days: macrophages take over, release cytokines and complement components. Lymphocytes-plasma cells-for immune response
4. Caseous necrosis
5. Frustrated phagocytosis of macrophages–>giant cells (Langhans)
   6, Persistent hypersensitivity leads to granuloma

Question 34

Acid fast stain?

Answer 34

Stain for mycobacteria

As they are not sensitive to Gram staining

Question 35

Mantoux test?

Answer 35

Synthetic tuberculin protein injected underneath skin, site checked 48-72 hours later, reaction indicates exposure to TB (active or latent disease, BCG vaccine or natural immunity)

Question 36

Primary complex and Ghon focus and complex in reference to TB?

Answer 36

Primary complex-local lung area in which the bacteria reside
Ghon focus-primary lesion that is usually asymptomatic
Ghon complex-lesion in lung due to TB, calcified focus of infection and associated lymph node

Question 37

Ranke complex?

Answer 37

An area seen in “healed” TB

Question 38

Define miliary TB, Pott’s disease and scrofula

Answer 38

Miliary TB: numerous small granulomas in many organs showing a wide TB distribution
Pott’s disease: TB in the vertebrae
Scrofula: TB infection of lymph nodes causing neck lymphadenopathy