Inflammation Flashcards
What is inflammation?
A reaction to injury or infection involving cells such as neutrophils and macrophages
What is acute inflammation?
Sudden onset - seconds to minutes
Short duration - hours to days
Usually resolves
Caused by neutrophils and monocytes
Initial response of tissue to injury
What is chronic inflammation?
Slow onset or sequel to acute
Subsequent and prolonged response to tissue injury
Long duration, longer onset, long last effects
May never resolve
Caused by lymphocytes, macrophages and plasma cells
What are the causes of chronic inflammation?
Causes:
Primary Chronic Inflammation
Resistance of infective agent, e.g. TB, leprosy
Endogenous materials, e.g. necrotic tissue
Exogenous materials, e.g. asbestos, silica
Autoimmune conditions, e.g. Hashimoto’s, rheumatoid arthritis
Primary granulomatous diseases, e.g. Chron’s, sarcoidosis
Transplant rejection
What is the macroscopic appearance of Chronic inflammation?
Chronic ulcer
Chronic abscess cavity
Granulomatous inflammation
Fibrosis
What is the microscopic appearance of chronic inflammation?
Characteristically lymphocytes, plasma cells and macrophages
Exudation is not a common feature
Evidence of continuing destruction
Possible tissue necrosis
What is the cellular cooperation in chronic inflammation?
B lymphocytes
-Transform into plasma cells and produce antibodies
T lymphocytes
-Responsible for cell-mediated immunity
Macrophages
-Respond to chemotactic stimuli
-Produce cytokines: Interferon alpha and beta, IL1, 6, 8, TNF-alpha
What are neutrophil polymorphs?
-Short lived cells -2 to 3 days
-First on the scene of acute inflammation
-Cytoplasmic granules full of enzymes that kill bacteria
-Usually die at the scene of inflammation
-Release chemicals that attract other inflammatory cells such as macrophages
-Polymorphic nuclei, cytoplasm has bags of enzymes
- White Blood cells
- Phagocytose debris and bacteria and contain lysosomes which kill and digest the bacteria
What are macrophages
-Long lived cells (weeks to months)
-Phagocytic properties
-Ingest bacteria and debris
-May carry debris away
-May present antigen to lymphocytes so secondary immune reaction is induced
-Mostly nucleus
- Doesnt make many proteins
- Immune memory cells
What are plasma cells
Very specialised
Creates antibodies
Lots of cytoplasm and endoplasmic reticulum
Endothelial cells
Line capillary blood vessels in areas of inflammation
Become sticky in areas of inflammation so inflammatory cells adhere to them
Become porous to allow inflammatory cells to pass into tissues
Grow into areas of damage to form new capillary vessels
Theyre very active
Produce nitric oxide to stop things from sticking to them
How does acute inflammation work?
In a normal endothelial cell precapillary sphincter is closed
In acute inflammation precapillary sphincter opens
Causes it to look red because capillaries are open and swollen as it has more blood and fluid in it - more fluid leaking out into tissue
Look back at pictures in ‘acute and chronic inflammation’ lecture
Acute inflammation component
Vascular component: dilation of vessels
Exudative component: vascular leakage of protein-rich fluid
Neutrophil polymorph: cells type recruited to tissue
Sequence of acute inflammation
- injury or infection
- neutrophils arrive and phagocytose and release enzymes
- macrophages arrive and phagocytose
- either resolution with clearance of inflammation or proression to chronic inflammation
- examples of acute (neutrophil-mediated) inflammation -
acute appendicitis, frostbite, Streptococcal sore throat
What does acute inflammation cause?
Microbial infections – bacteria, viruses
Hypersensitivity reactions – parasites
Physical agents – trauma, heat, cold
Chemicals – corrosives, acids
Bacterial toxins
Tissue necrosis – ischemic infarction
What is the appearance of acute inflammation?
Rubor – redness; due to dilation of small vessels)
Calor – heat; only seen peripherally
Tumor – swelling; results from oedema or a physical mass
Dolor - pain
Loss of function
What is neutrophil polymorph emigration?
- Migration of neutrophils
-Due to increase in plasma viscosity and slowing of flow due to injury, neutrophils migrate to plasmatic zone - Adhesion of neutrophils
-Adhesion to the vascular endothelium occurs in venules – called pavementing - Neutrophil emigration
-Neutrophils pass through endothelial cells, onto the basal lamina and then the vessel wall - Diapedesis
RBCs may also escape from vessels, this is a passive process and indicates severe vascular injury
What are the outcomes of acute inflammation?
1.Resolution
2.Suppuration
3.Organisation
4.Progression
Describe resolution
The complete restoration of tissues to normal
There is minimal cell death and rapid destruction of the causal agent
E.g. acute lobar pneumonia
Describe Suppuration
Formation of pus
This becomes surrounded by a pyogenic membrane, which is the start of healing
Leads to scarring
Describe organisation
Replacement by granulation tissue
New capillaries grow into the inflammatory exudate, macrophages migrate and fibrosis occurs
Describe progression
Causative agent is not removed so there is progression to chronic inflammation
What is sepsis
All capillaries in body opened all at once
We do not have enough blood to fill them all
What are fibroblasts?
Long lived cells
Form collagen in areas of chronic inflammation and repair
Spindly shaped cells
Lots of endoplasmic reticulum
Produces collagenous connective tissue in scarring following some types of inflammation
What happens in fibrosis
When fibroblasts produce lots of collagen
What is an example of acute inflammation?
Acute appendicitis
-Unknown precipitating factor
-Neutrophils appear
-Blood vessels dilate
-Inflammation of serosal surface occurs
-Pain felt
-Appendix either surgically removed or inflammation resolves or appendix bursts with generalised peritonitis and possible death
What is an example of chronic inflammation?
Tuberculosis
-No initial acute inflammation
-Mycobacteria ingested by macrophages
-Macrophages often fail to kill the mycobacteria
-Lymphocytes appear
-Macrophages appear
-Fibrosis occurs
Steps in chronic inflammation
- either progression from acute inflammation or starts as
‘chronic’ inflammation such as infectious mononucleosis
(thus better term is macrophage/lymphocyte-mediated
inflammation) - no or very few neutrophils
- macrophages and lymphocytes, then usually fibroblasts
- can resolve if no tissue damage (e.g. viral infection like
glandular fever) but often ends up with repair and formation of scar tissue
What is a granuloma
A particular sort of inflammation
An aggregate of epithelioid histocytes
Points to certain diagnosis such as TB or Crohn’s disease
Granulomas and eosinophil presence indicates a parasite
What is a histamine
A chemical mediator of acute inflammation
What does an antihistamine do?
Stops inflammation
Whats an example of an antihistamine?
Benadryl