ChronInflam

Question 1

Formation of granulation tissue mechanism and function

Answer 1

• Capillaries grow
• Plasma proteins accessed
• Macrophages
• Fibroblasts lay down collagen
• Collagen replaces inflammatory exudate
• Tissue defects are patched
• Replace necrotic tissue
• Pulls together tissue

Question 2

Granulation tissue can progress to

Answer 2

• Fibrous tissue - scar
• Fibrosis as a problem: adhesion between loops of bowel following peritonitis
• Can progress to chronic inflammation

Question 3

Cells types involved in chronic inflammation

Answer 3

• Lymphocytes
• Plasma cells
• Macrophages
• Fibroblasts

Question 4

Lymphocytes

Answer 4

• Part of immune system
• Small round cells with lots of subtypes and functions
• 2 main types: T cells and B cells
• Main functions: immune response and memory

Question 5

T Cells

Answer 5

• Produce cytokines: attract and hold macrophages, excite macrophages, get other cells involved, permeability
• T-cells produce interferons: antiviral effects and attract and stimulate other cells

Question 6

B Cells

Answer 6

• Differentiate to plasma cells
• Facilitate immune response and have an immune memory
• Collaborate with macrophages: antigen presenting cells

Question 7

Plasma cells

Answer 7

• Differentiated B cell
• Antibody production
• Intermediate size

Question 8

Macrophages

Answer 8

• Remove debris
• Role in immune system, antigen presenting cell
• Bone marrow, blood tissues

Question 9

What can a macrophage become?

Answer 9

• Monocyte
• Histiocyte
• Activate macrophage
• Epitheloid cell (looks like an epithelial cell but is a macrophage)
• Giant cell

Question 10

Mechanism of macrophages

Answer 10

• Move from blood
• Take over from neutrophils
• Contain enzymes
• Produce interferons and other chemicals which destroy and influence
• Crux of chronic inflammation is if these responses tend not recede

Question 11

Fibroblasts

Answer 11

• Motile cells
• Metabolically active
• Make and assemble structural proteins: collagens and various other types

Question 12

Causes of primary chronic inflammation

Answer 12

• Material resistant to digestion
• Exogenous substance
• Endogenous substances
• Granulomatous inflammation common in all of these

Question 13

Material resistant to digestion

Answer 13

• Mycobacteria, Brucella, viruses

- Cell wall resistant to enzymes

Question 14

Exogenous substances

Answer 14

• Sutures, metal and plastic

- You don’t get an immune response as they’re sterile but you get chronic inflammation

Question 15

Endogenous substances

Answer 15

• Necrotic tissue, keratin, hair

- Similar concept as exogenous, you can’t get phagocytosed

Question 16

Clinical presentations of chronic inflammation

Answer 16

• No specific sore bit as an anatomical pointer
• Malaise and weight loss
• Loss of function

Question 17

Loss of function in chronic inflammation examples

Answer 17

• Autoimmune thyroiditis (functional gland destruction) - hypothyroidism
• Crohn’s disease (GI tract ulceration and fibrosis) - pain, diarrhoea, gut obstruction
• Leprosy (cutaneous nerve destruction) - loss of sensation, destroying the tissue

Question 18

Why do we see chronic inflammation?

Answer 18

• Arising from acute inflammation: large volume of damage, inability to remove debris, fails to resolve (super infection)
• Primary lesion: no preceding acute phase, only see chronic changes

Question 19

Adverse effects of tissue scarring

Answer 19

• After granulation tissue is characteristic of organisation
• A scar can form but this can lead to fibrosis which means there are adhesions between loops of bowel following peritonitis
• Can progress to chronic inflammation

Question 20

Granulomatous inflammation characteristics

Answer 20

• Particular kind of inflammatory response characterised by granulomas in tissues and organs
• Stimulated by indigestible antigen. E.g. macrophages can’t get rid
• Serious infections and idiopathic diseases
• Diseases important on a global scale are granulomatous inflammatory diseases

Question 21

Granulomas

Answer 21

• Aggregates of epithelioid macrophages in tissue
• May contain giant cells
• May surround dead material
• May be surrounded by lymphocytes
• Contain neutrophils, eosinophils
• May be in response to indigestible antigen
• Many are type IV hypersensitivity reactions

Question 22

Giant cells

Answer 22

Granulomas comprise of epithelioid histiocytes (aka macrophages)

• Large cytoplasm, multiple nuclei
• Several types
• Giant cells can be present even when there is no granuloma present

Question 23

Examples of types of giant cell

Answer 23

• Langhans type
• Foreign body type
• Silicone associated

Question 24

Langhans type

Answer 24

• Classically found in TB
• Peripheral rim of nuclei
• Large eosinophillic cytoplasm

Question 25

Foreign body type

Answer 25

- Often associated with pyogenic granulation tissue - Acutely inflamed - Neutrophils, pus - Typically you can see slits in the cell which could be acetabular particules or glass

Question 26

Silicone associated

Answer 26

- Rupture silicone implants: usually but not always breast, vacuoles contain leaked silicone - Produces granulomatous response - Can be found around about the affected area and axillary lymph nodes - You can also see the typical bubbles in the histology dye to the inability to dissolve`

Question 27

Examples of non-infective granulomas

Answer 27

- Rheumatoid disease: tissue specific autoimmune disease - Sarcoidosis: classical clinical picture, unknown cause, fibrosis in the lung fields - Crohn's disease: chronic inflammatory bowel disease, unknown cause. Ulceration of mucosa, you can see the mucous disappear into granulation tissue microscopically

Question 28

Factors involved in promoting healing and repair

Answer 28

1. Phase of acute inflammation 2. Granulation tissue formation 3. Local angiogenesis - new vessels grow 4. Fibrosis and scar formation

Question 29

Granulation tissue formation

Answer 29

- Healing by primary intention: In surgical wounds you allow for a minimal gap, which means a small amount of granulation tissue - Healing by secondary intention: On larger wounds, there is a lot of granulation tissue ingrowth in a lot of different directions which means there is a lot more contraction and scarring as it crosslinks.

Question 30

Fibrosis and scar formation

Answer 30

- Phagocytosis of fibrin - Myofibroblasts move in and lay down collagen - Contraction of scar

Question 31

Overall favoured wound healing

Answer 31

- Cleanliness - Apposition of edges (no haematoma) - Sound nutrition: wound healing is a catabolic process - Metabolic stability and normality - Normal inflammatory and coagulation mechanisms

Question 32

Angiogenesis

Answer 32

- New vessels form capillary buds - Vascular Endothelial Growth Factor (VEGF) released by hypoxic cells stimulates proliferation - Enzyme blood supply to enter damaged tissue

Question 33

Nature of Process of Angiogenesis

Answer 33

- Limits propagation and reinstates flow - Malignant tumours: angiogenesisas tumour is hypoxic, stimulates tissue around it to improve blood supply - Fibrosis and scarring in atherosclerosis: similarities with chronic inflammation

Question 34

Impaired wound healing

Answer 34

- Dirty, gaping wound, large haematoma - Poorly nourished, lack of vitamins C, A - Abnormal CHO metabolism, diabetes, corticosteroid therapy - Inhibition of angiogenesis

Question 35

Fracture healing 1

Answer 35

- Same principle as wound healing - Fracture and a haematoma (sub-periosteal haemorrhage) - Bits of dead bone and soft tissue are mixed together in a bit of a mess - Acute inflammation, organisation, granulation tissue and macrophages remove debris - Granulation tissues contain osteoblasts as well as fibroblasts

Question 36

Fracture healing 2. New bone

Answer 36

- Osteoblasts lay down woven bone - Nodules of cartilage present - Followed by bone remodelling: osteoclasts remove dead bone, progressive replacement of woven bone by lamellar bone, reformation of cortical and trabecular bone