Chronic inflammation

Question 1

Define chronic inflammation?

Answer 1

inflammation in which the cell population is especially
lymphocytes
plasma cells (production of antibodies)
macrophages (phagocytes and involved in the antigen presentation to the immune response)

Features of tissue or organ damage, (necrosis), loss of function

healing and repair
-granulation tissue
-scarring and fibrosis

may follow from ongoing acute inflammation
and commonly does
“acute on chronic inflammation”

but also arises as primary pathology
tends to be long-term

Question 2

Describe the clinical presentation of chronic inflammation?

Answer 2

often no specific “sore bit”

malaise and weight loss
tuberculosis (lung, lymph node, bone, kidney, skin) – systemic effect

loss of function
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

Question 3

Where do we see chronic inflammation?

Answer 3

arising from acute inflammation
follows on from acute
large volume of damage
inability to remove debris
fails to resolve – ongoing acute insult

arising as a primary lesion
no preceding acute phase
only see chronic changes

Question 4

What is angiogenesis?

Answer 4

new vessels form- capillary buds (growing off existing vessels)
Vascular Endothelial Growth Factor (VEGF) released by hypoxic cells and stimulates proliferation
enzyme secretion aids process
enable blood supply to enter damaged tissue

Question 5

Why is VEGF (Vascular Endothelial Growth Factor) useful?

Answer 5

inhibit endothelial cell growth and is actually used therapeutically in some cancers.

Question 6

Describe the generic nature of angiogenesis?

Answer 6

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

Question 7

How is wound repaired?

Answer 7

capillaries grow into inflammatory mass:
for access of plasma proteins
macrophages from blood and tissue
fibroblasts lay down collagen
repairs damaged tissue
collagen replaces inflammatory exudate

In doing so
granulation tissue patches tissue defects
replaces dead or necrotic tissue
granulation tissue contracts and pulls edges of damage (eg wound) together

Question 8

Describe the acute and chronic interface?

Answer 8

acute inflammation

…

mixture of acute and chronic inflammation (e.g. infected wound)
exudate, neutrophils
lymphocytes, plasma cells, fibroblasts, fibrosis (Components of chronic)

chronic inflammation (once inflammation has resolved, acute inflammation is resolved and the infection is stopped) -still have tissue damage and so chronic inflammation and formation of scar

Question 9

What is pyogenic granulation tissue?

Answer 9

acute and chronic
pus formation in the presence of granulation tissue

pyogenic( neutrophils)
granulation (chronic inflammatory components)

Question 10

What are some products of granulation tissue?

Answer 10

fibrous tissue - scar
eg small firm blemish on skin

fibrosis as a problem
adhesions between loops of bowel following peritonitis

chronic inflammation

Question 11

Describe primary chronic inflammation?

Answer 11

-autoimmune disease

autoantibodies directed against own cell and tissue components – autoantigens

damage or destroy organs, tissues, cells, cell components

thyroiditis, rheumatoid disease, pernicious anaemia (chief/parietal cells), systemic lupus erythematosis (nuclear antigen)

-lymphocytes, plasma cells, macrophages, fibrosis

-resistance to digestion
mycobacteria, brucella, viruses where cell wall or organism are resistant to enzymes

-exogenous substances
sutures, metal and plastic e.g. joint replacements, mineral crystals, glass
not provoke immune response

-endogenous substances
-necrotic tissue, keratin, hair
cannot easily be phagocytosed

Question 12

What are the cells and tissue components involved in chronic inflammation?

Answer 12

cells and their roles:
lymphocytes
plasma cells
macrophages
fibroblasts

tissue components:
granulation tissue
collagen

Question 13

Describe lymphocytes?

Answer 13

cells that are part of immune system

small round cells with lots of subtypes and functions

main types of lymphocyte:
T-cell
B-cell

main functions:
immune response
immune memory

Question 14

Describe plasma cells?

Answer 14

differentiated B-cell
characteristic morphology
antibody production
intermediate size

Question 15

Describe how B cells work?

Answer 15

differentiate to plasma cells and produce antibodies and in doing so
facilitate adaptive immune response

act with macrophages - antigen presenting capacity

lymphocytes produce immune memory

Question 16

Describe how T cells work?

Answer 16

T-cells produce cytokines- attract and hold macrophages
activate cells, eg other lymphocytes, macrophages
alter permeability of endothelial cells

T-cells produce interferons-
antiviral effects
attract and stimulate other cells

T cells also can damage and kill (lyse) other cells and destroy antigen
chemical mechanisms - granule proteins
(more specific- cellular immune response)

Question 17

Describe how NK cells work?

Answer 17

NK cell destroy antigens and cells
chemical mechanisms - granule proteins
innate immunity

Question 18

Describe how macrophages work?

Answer 18

antigen presenting cell
floating around in peripheral blood (monocyte),tissue (histiocytes) , activated macrophage, epithelioid cells, giant cell (nucleus multiplied)

-come from bone marrow but also in peripheral blood

Question 19

Characteristics of macrophages?

Answer 19

mobile phagocyte move from blood
long lived unlike neutrophils
take over from neutrophils
contain enzymes e.g. lysozyme
produce interferons (can destroy invading organisms like viruses) and other chemicals
or themselves influence processes or other cells to do that kind of work

Question 20

Give characteristics of granulomatous inflammation?

Answer 20

characterised by presence of granulomas (collections of macrophages) (granulomata) in tissues and organs

stimulated by indigestible antigen
body cannot get rid of it

many serious infectious and idiopathic (= no known cause) diseases produce granulomas

these diseases important on global scale - causes a lot of morbidity and mortality

Question 21

Give characteristics of 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
response to indigestible antigen
many are type IV hypersensitivity reactions

Question 22

Describe what giant cells are and how they are thought to have been formed?

Answer 22

fusion of macrophages to form larger cells?
large cytoplasm; multiple nuclei
several types
don’t always need granuloma for giant cells to be present

Question 23

Give characteristics of langhans type giant cell?

Answer 23

classically found in TB
peripheral rim of nuclei
large eosinophilic cytoplasm

Question 24

Give characteristics of the foreign body giant cell type?

Answer 24

often associated with pyogenic granulation tissue

acutely inflamed
neutrophils, pus
organisation
giant cells

eg pilonidal abscess (ingrown nasal hair- can’t be digested)

Question 25

Give characteristics of silicone associated giant cells?

Answer 25

ruptured silicone implants

usually but not always breast

vacuoles contain leaked silicone

Question 26

What is the bug of tuberculosis?

Answer 26

mycobacterium tuberculosis

Question 27

What is the bug of leprosy?

Answer 27

mycobacterium leprae

Question 28

What is the bug of syphilis?

Answer 28

treponema pallidum

Question 29

Give examples of non -infective granulomatous conditions?

Answer 29

rheumatoid disease- tissue specific auto-immune disease , ? cause

sarcoidosis- granulomas developing in organs

Crohn’s Disease- chronic inflammatory bowel disease

Question 30

What are the steps of wound healing?

Answer 30

acute phase of acute inflammation
granulation tissue formation
local angiogenesis – new vessels grow
fibrosis and scar formation

Question 31

Describe what happens in surgical wound healing?

Answer 31

pull edges as close together using suture material
minimal gap-blood clot
small amount of granulation tissue
small linear scar

Question 32

Describe what happens in healing of larger defects?

Answer 32

lot of tissue damage
lots of granulation tissue ingrowth
contracting and scarring

Question 33

How do we favour wound healing?

Answer 33

cleanliness
apposition of edges (no haematoma- easy access for bugs)
sound nutrition
metabolic stability and normality
normal inflammatory and coagulation mechanisms
note local mediators

Question 34

Summary of sequence of events in wound healing?

Answer 34

injury, blood clot, acute inflammation, deposition of 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 35

What contributes to impaired wound healing?

Answer 35

dirty, gaping wound, large haematoma
poorly nourished, lack of vitamins C, A
abnormal CHO metabolism, diabetes, corticosteroid therapy
inhibition of angiogenesis

Question 36

Differences between wound healing and fracture healing?

Answer 36

same principles as healing at any site
modified by situation in bone (bone has matrix)
have to repair bony structure as well as soft tissue

Question 37

What are the sequence of events in wound healing?

Answer 37

trauma, fracture, haematoma
bits of dead bone and soft tissue
acute inflammation, organisation, granulation tissue, macrophages remove debris
…. difference in bone…..
granulation tissue contains osteoblasts ( lay down bone matrix) as well as fibroblasts

Question 38

What are the steps involved in callus (lump of tissue with remodelling going on) formation?

Answer 38

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