Inflammation and Healing Flashcards
define inflammation
local tissue response to injury
name some beneficial effects of inflammation
Destruction of invading microorganisms.
Walling off of an abscess cavity - preventing spread of infection.
give examples of how inflammation may cause disease
An abscess in brain = space-occupying lesion, compressing surrounding structure.
Fibrosis from chronic inflammation - distort tissues, alter function.
define acute inflammation
the initial and often transient series of tissue reactions to injury
define chronic inflammation
subsequent and often prolonged tissue reactions following the initial response
what type of cell is characteristically recruited in acute inflammation?
neutrophil polymorph
list the possible outcomes of acute inflammation
suppuration (e.g. abscess)
organisation
progression to chronic inflammation
resolution
what is the vascular component of acute inflammation?
dilatation of vessels
what is the exudative component of acute inflammation?
vascular leakage of protein-rich fluid
list the causes of acute inflammation
microbial infections; hypersensitivity reactions; physical agents; chemicals; bacterial toxins; tissue necrosis (e.g. ischaemic infarction)
name some physical agents that may cause acute inflammation
trauma; ionising radiation; heat; cold
name some chemical agents that may cause acute inflammation
corrosives; acids; alkalis; reducing agents
describe how a microbial infection causes acute inflammation
viruses - death of individual cells by intracellular multiplication.
bacteria - release of exotoxins/endotoxins
how does a hypersensitivity reaction cause acute inflammation?
inappropriate/excessive immune reaction damages tissues
define tissue necrosis
death of tissues from lack of oxygen/nutrients resulting from inadequate blood flow (infarction)
what are the macroscopic appearances of acute inflammation?
redness - rubor heat - calor swelling - tumor pain - dolor loss of function
what causes redness/rubor in acute inflammation?
dilatation of small blood vessels within the damaged area
what causes the heat associated with inflammation of peripheral parts of the body?
increased blood flow (hyperaemia) through the region - vascular dilatation and delivery of warm blood
what causes swelling associated with acute inflammation?
oedema - accumulation of fluid in extravascular space as part of fluid exudate.
also physical mass of inflammatory cells.
what causes the pain associated with acute inflammation?
stretching/distortion of tissues due to oedema.
pus under pressure in an abscess cavity.
chemical mediators (bradykinin, prostaglandins, serotonin)
what causes loss of function in acute inflammation?
movement of inflamed area is consciously and reflexly inhibited by pain.
severe swelling may limit movement.
If there are neutrophil polymorph’s present, is it acute or chronic inflammation?
acute
what are the three processes involved in acute inflammation?
- changes in vessel calibre and flow
- increased vascular permeability and formation of fluid exudate
- formation of cellular exudate - migration of neutrophil polymorphs into extravascular space
describe the changes in vessel calibre seen in acute inflammation
dilatation of arteriole
opening of pre-capillary sphincter
most capillaries full of blood
give some examples of chemical mediators that increase vascular permeability in acute inflammation?
histamine
bradykinin
nitric oxide
what is exudation?
net escape of protein-rich fluid from blood vessels
what proteins are present in the fluid exudate seen in inflammation?
immunoglobulins
coagulation factors - fibrin deposition
describe the process of neutrophil polymorph migration into tissues in acute inflammation
- margination of neutrophils
- pavementing of neutrophils
- pass between endothelial cells
- pass through basal lamina and migrate into adventitia
what is the main source of histamine?
mast cells, stored in granules in their cytoplasm
what stimulates histamine release?
C3a and C5a
lysosomal proteins released from neutrophils
what is the effect of histamine?
dilates vessel
increases vascular permeability
describe the role of tissue macrophages in acute inflammation
secrete chemical mediators that attract neutrophil polymorphs to the site
describe the role of the lymphatics in acute inflammation
channels dilate, and drain away the oedema fluid, limiting swelling.
antigens are carried to regional lymph nodes for recognition by lymphocytes.
what is the major role of neutrophil polymorphs in acute inflammation?
PHAGOCYTOSIS
describe the steps of phagocytosis
- adhesion of particle to cell surface (opsonisation facilitates)
- ingestion of particle by sending out pseudopodia
- fusion of lysosomes with the phagosome - phagolysosome
- intracellular killing of microorganism
list the five terms used to describe special macroscopic appearances of acute inflammation - as dependent on the type of tissue involved and the type of agent provoking the inflammation.
serous suppurative (purulent) inflammation membranous inflammation pseudomembranous inflammation necrotising (gangrenous) inflammation
describe some beneficial effects of acute inflammation
dilution of toxins - allows them to be carried away in lymphatic.
entry of antibodies - phagocytosis, toxin neutralisation.
transport of drugs (antibiotics) to inflamed area
fibrin formation impedes movement of microorganisms.
describe some harmful effects of acute inflammation
vascular damage.
swelling - e.g. airway obstruction
inappropriate inflammatory response - type 1 hypersensitivity reactions (e.g. hayfever)
what factors determine the outcome of acute inflammation?
type of tissue involved.
amount of tissue destruction.
both of these depend on nature of injuring agent.
what is the usual result of acute inflammation?
resolution
what causes acute inflammation to progress to suppuration?
excessive exudate
what causes acute inflammation to progress to organisation?
excessive necrosis
what causes acute inflammation to progress to chronic inflammation?
persistent causal agent
what conditions favour resolution of acute inflammation?
minimal cell death/tissue damage.
occurred in organ with regenerative capacity (e.g. liver)
rapid destruction of causal agent
rapid removal of fluid/debris - good local vascular drainage.
what is pus?
a mixture of living/dying/dead neutrophils and bacteria, cellular debris and possibly globules of lipid
what conditions favour progression of acute inflammation to organisation?
large amounts of fibrin.
lots of necrotic tissue.
exudate and debris not removed/discharged
what are the systemic effects of inflammation?
pyrexia. constitutional symptoms. weight loss. reactive hyperplasia of reticuloendothelial system. haematological changes. amyloidosis.
what are the predominant cells seen in chronic inflammation?
lymphocytes, plasma cells and macrophages
also fibroblasts and multinucleate giant cells
list the causes of chronic inflammation
primary chronic inflammation
transplant rejection
progression from acute inflammation
recurrent episodes of acute inflammation
give some examples of causes of primary chronic inflammation
TB, leprosy, viral infections - resistance to phagocytosis.
endogenous - necrotic adipose tissue, bone
exogenous - silica, asbestos, sutures, prostheses
autoimmune diseases
chronic IBD eg ulcerative colitis
primary granulomatous diseases - Crohn’s, sarcoidosis
what are the macroscopic appearances of chronic inflammation?
chronic ulcer chronic abscess cavity thickening of wall of a hollow viscus granulomatous inflammation fibrosis
describe the cellular infiltrate seen in chronic inflammation
lymphocytes, plasma cells and macrophages.
possibly a few eosinophil polymorphs, but no neutrophil polymorphs.
some macrophages may form neutrophil giant cells.
describe the differences between macrophages and neutrophil polymorphs
macrophages can ingest a wider range of materials.
neutrophil polymorphs last 3 days - destroy themself when they ingest microorganisms.
Macrophages are long-lived - if they can’t kill ingest microorganisms, they will harbour them.
give some examples of organisms that can survive inside macrophages
mycobacteria - M tuberculosis and M leprae.
histoplasma capsulatum.
what are macrophages derived from? what system does this make them part of?
blood monocytes.
mononclear phagocyte system aka reticuloendothelial system.
define a granuloma
aggregation of epithelioid histiocytes
what cell types does a granuloma contain?
epithelioid histiocytes
also possible - lymphocytes and histiocytic giant cells
give some examples of granulomatous disease
Tuberculosis
leprosy
Crohn’s disease
sarcoidosis
describe the morphology of an epithelioid histiocyte
vague histological resemblance to epithelial cells. large vesicular nuclei eosinophilic cytoplasm. elongated. arranged in clusters.
name a major secretory product of epithelioid histiocytes
angiotensin-converting enzyme
can use ACE levels as a marker for systemic granulomatous disease (e.g. sarcoidosis)
what does association of granulomas with eosinophils indicate?
parasitic infection (e.g. worms)
What type of granuloma is seen in TB?
granuloma with caseating necrosis
what type of cells make multinucleate giant cells in granuloma?
histiocytes
list some common causes of granuloma
TB, leprosy, fungi, parasites, syphilis.
materials that resist ingestion - keratin, necrotic bone, talk, silica.
beryllium
Crohn’s disease; sarcoidosis; Wegener’s granulomatosis
what causes formation of histiocytic giant cells?
accumulation of matter that is indigestible by macrophages.
especially when foreign particles are too large to be ingested by a single macrophage.
describe the appearance of Langhans giant cells
horseshoe arrangement of peripheral nuclei at one pole of the cell - characteristic in TB
what type of giant cell is characteristic in TB
Langhans giant cell
describe the appearance of foreign body giant cells
large cells with nuclei randomly scattered throughout cytoplasm
what must be present for there to be a granuloma?
EPITHELIOID HISTIOCYTES - giant cells are commonly seen in granulomas, but without epithelioid histiocytes, it’s not a granuloma
describe the appearance of Touton giant cells
central ring of nuclei, peripheral to which there is lipid material
list some of the roles of chronic inflammation in systemic/organ-specific diseases
myocardial fibrosis after MI.
initiation and propagation, and progression, of cancer e.g. ulcerative colitis, tissue response to asbestos fibres.
atheroma development.
tissue injury associated with neurodegenerative disorders e.g. MS
differentiate between resolution and repair
Resolution - initiating factor removed, tissue undamaged/able to regenerate.
Repair - initiating factor still present, tissue damaged and unable to regenerate.
define repair
replacement of damaged tissue by fibrous tissue.
collagen is produced by fibroblasts.
list types of cell that regnerate
hepatocytes pneumocytes all blood cells gut epithelium skin epithelium osteocytes
what cell types don’t regenerate?
myocardial cells
neurones
describe the appearance of coagulative necrosis
firm, pale area with ghost outlines on microscopy
describe the appearance of colliquative necrosis. where is this seen?
dead area is liquefied.
seen in the brain.
what disease shows caseous necrosis? what is the appearance of this?
TB.
pale yellow semi-solid material.
define gangrene, and its appearance
necrosis with putrefaction.
follows vascular occlusion or certain infections.
black.
what is fibrinoid necrosis?
a microscopic feature in arterioles in malignant hypertension
list the types of necrosis
coagulative colliquative caseous gangrene fibrinoid fat necrosis
what causes fat necrosis?
trauma.
pancreatitis.
give an example and explanation of complete restitution
complete restoration following loss of part of a regenerative cell population - e.g. healing of a minor skin abrasion.
define organisation of tissues
repair of specialised tissues by formation of fibrous scar.
how does organisation occur?
production of granulation tissue, laid on a scaffold of fibrin, and removal of dead tissue by phagocytosis.
describe the formation of granulation tissue
capillary endothelial cells grow and proliferate into damaged area - open into vascular channels, arranged as loops.
fibroblasts divide, secrete collagen/matrix, and acquire bundles of muscle fibres - myofibroblasts, function as SMCs.
contract to reduce wound size.
what does granulation tissue consist of?
loops of capillaries supported by myofibroblasts.
possible inflammatory cells.
what causes wound contraction? what is its purpose?
contraction of myofibroblasts in granulation tissue. collagen is secreted, forming a scar.
reduces volume of tissue for repair - but this produces a scar
describe “healing by first intention”
apposed wound margins are joined by fibrin deposition, which is then replaced by collagen and covered by epidermal growth
describe “healing by second intention”
wound margins are unapposed due to extensive tissue damage.
tissue defect fills with granulation tissue.
epithelial regeneration to cover surface.
granulation tissue contracts - scar formation
list some complications of scarring/wound contraction
stenosis (narrowing) - if tissue damage goes around the lumen of a tube
obstruction of a tube due a stricture
permanent shortening of a muscle - contracture
burns can result in a lot of contraction - cosmetic damage, impaired motility
describe abscess formation
- pus accumulates in a tissue
- becomes surrounded by a ‘pyogenic membrane’
- this consists of sprouting capillaries, neutrophils and occasional fibroblasts
- this will eventually result in granulation and scarring
what challenge does an abscess present for treating bacterial infection?
bacteria within abscess cavity are relatively inaccessible to antibodies and antibiotic drugs
describe the difference between a bacterial endotoxin and an exotoxin
exotoxin = synthesised inside the cell endotoxin = associated with cell wall
