Chronic inflammation mw%% XXXXXXXXXXXXXXXXXXX

Question 1

Define chronic inflammation?

Answer 1

•Inflammation in which the cell population is especially

–Lymphocytes

–Plasma cells

–Macrophages

• Features tissue or organ damage, (necrosis), loss of function.
• Healing and repair

–granulation tissue

–scarring and fibrosis

• May follow from ongoing acute inflammation
• But also arises as primary pathology
• Tends to be long-term

Question 2

How is chronic inflamtion represented Clinically?

Answer 2

• Often no specific “sore bit”
• Malaise and weight loss

–tuberculosis (lung, lymph node) – systemic effect

•Loss of function

–autoimmune thyroiditis (functional gland destruction) – hypothyroidism

Question 3

When do we see chronic inflammation?

Answer 3

•Arising from acute inflammation

–follows on from acute

–inability to remove debris

–fails to resolve – ongoing acute insult

•Arising as a primary lesion

–only see chronic changes

Question 4

What is the big picture of granulation in organisation as an outcome of acute inflammation?

Answer 4

• Granulation tissue is characteristic of organisation
• Results in healing and repair
• Leads to fibrosis and formation of a scar

Question 5

What is the granulation tissue mechanism and function?

Answer 5

• Capillaries grow into inflammatory mass
• Macrophages from blood and tissue
• Fibroblasts lay down collagen to repair damaged tissue
• Collagen replaces inflammatory exudate
• patches tissue defects
• replaces dead or necrotic tissue
• contracts and pulls together

Question 6

What are the products of granulation tissue?

Answer 6

• Fbrous tissue - scar
• Fibrosis as a problem

–adhesions between loops of bowel following peritonitis

•Can progress to chronic inflammation

Question 7

What are the type of diseases which occur as a primary chronic inflammation?

Answer 7

•Autoimmune disease:

–Autoantibodies directed against own cell and tissue components – autoantigens

–Damage or destroy organs, tissues, cells, cell components

–Thyroiditis, rheumatoid disease,

Question 8

What are the main cells involved in primary chronic inflamation?

Answer 8

• Lymphocytes
• Plasma cells
• Macrophages
• Fibrosis

Question 9

What are the causes of chronic inflamation?

Answer 9

1. Material resistant to digestion

–Mycobacteria

2. Exogenous substances

– Metal

3. Endogenous substances

– Keratin

–Cannot easily be phagocytosed

4.Granulomatous inflammation common

Question 10

What are lymphocytes?

Answer 10

• Cells that are part of immune system
• Main types of lymphocyte

–T-cell

–B-cell

•Main functions

–Immune response

–Immune memory

Question 11

What is a Plasma cell?

Answer 11

• Differentiated B-cell
• Antibody production

Question 12

Briefly describe B-cell mechanisms?

Answer 12

•Differentiate to plasma cells

–antibodies

• Facilitate immune response
• Act with macrophages

–antigen presenting capacity

•Immune memory

Question 13

Briefly describe T-cell mechanisms?

Answer 13

•T-cells produce cytokines

–Attract and hold macrophages

–Activate macrophages

–Other cells eg lymphocytes

•Damage and kill (lyse) other cells and destroy antigen

–Chemical mechanisms - granule proteins

Question 14

Briefly describe NK-cell mechanisms?

Answer 14

•NK cell destroy antigens and cells

–chemical mechanisms - granule proteins

Question 15

what are Macrophages?

Answer 15

• Removes debris
• Role in immune system - antigen presenting cell
• Monocyte, histiocyte, activated macrophage, epithelioid cell, giant cell
• Bone marrow, blood tissues

Question 16

Briefly describe macrophage mechanisms?

Answer 16

• Motile phagocyte move from blood
• Long lived
• Take over from neutrophils
• Contain enzymes eg lysozyme
• Produce interferons and other chemicals

–destroy, influence process

Question 17

What are fibroblasts and their function?

Answer 17

• Motile cells
• Metabolically active
• Make and assemble structural proteins

–collagens

–various types

Question 18

Summary of outcome

Answer 18

• Ongoing tissue damage and destruction
• Insidious loss of function
• Cellular and stromal response

–granulation tissue, angiogenesis

• Scarring and fibrosis
• Granuloma formation

Question 19

Granulomatous inflammation

Answer 19

• Characterised by presence of granulomas (granulomata) in tissues and organs
• Stimulated by indigestible antigen

–body cannot get rid of it

•Many serious infectious and idiopathic (= no known cause) diseases

Question 20

Granulomas

Answer 20

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

Question 21

Giant cells

Answer 21

• Granulomas comprise epithelioid histioytes (macrophages)
• ? fusion of macrophages to form larger cells
• Large cytoplasm; multiple nuclei

–several types

•Not always granuloma for giant cells to be present

Question 22

Foreign body type

Answer 22

•Often associated with pyogenic granulation tissue

–acutely inflamed

–neutrophils, pus

–organisation

–giant cells

•eg pilonidal abscess

Question 23

Silicone associated

Answer 23

•Ruptured silicone implants

–usually but not always breast

–vacuoles contain leaked silicone

Question 24

Warthin-Finkeldy type

Answer 24

• Rarely see in measles
• Central cluster of nuclei

Question 25

Infectious granulomatous diseases – examples relevant to global health

Answer 25

• Tuberculosis – Mycobacterium tuberculosis
• Leprosy – Mycobacterium leprae
• Syphilis – Treponema pallidum

Question 26

Non-infective granulomas - examples

Answer 26

• Rheumatoid disease - tissue specific auto-immune disease, ? cause
• Sarcoidosis – classical clinical picture, ? cause
• Crohn’s disease – chronic inflammatory bowel disease, ? cause

Question 27

Wound healing

Answer 27

• Process of repair of tissue damage
• Like any healing process after any injury
• Phase of acute inflammation
• Granulation tissue formation
• Local angiogenesis – new vessels grow
• Fibrosis and scar formation

Question 28

Sequence of events

Answer 28

• Injury, blood clot, acute inflammation, fibrin
• Many growth factors and cytokines involved
• Granulation tissue growth - angiogenesis
• Phagocytosis of fibrin
• Myofibroblasts move in and lay down collagen
• Contraction of scar
• Re-epithelialisation

Question 29

Favouring wound healing

Answer 29

• Cleanliness
• Apposition of edges (no haematoma)
• Sound nutrition
• Metabolic stability and normality
• Normal inflammatory and coagulation mechanisms
• Note local mediators

Question 30

Impaired wound healing

Answer 30

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

Question 31

Fracture healing

Answer 31

• Same principles as healing at any site
• Modified by situation in bone
• Have to repair bony structure as well as soft tissue

Question 32

Sequence of events

Answer 32

• Trauma, fracture, haematoma
• Bits of dead bone and soft tissue
• Acute inflammation, organisation, granulation tissue, macrophages remove debris
• Granulation tissue contains osteoblasts as well as fibroblasts

Question 33

Callus formation

Answer 33

• 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

Question 34

Angiogenesis

Answer 34

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

Question 35

Generic nature of process

Answer 35

•Angiogenesis and organisation in thrombosis

–limits thrombus propagation

–reinstatement of flow

•Angiogenesis in malignant tumours

–angiogenesis occurs as tumour grows

–potential for therapeutic control

•Fibrosis and scarring in atherosclerosis

–similarities with chronic inflammation