2 - Acute Inflammation Flashcards
What is inflammation
The body’s response to tissue injury that has caused necrosis in the tissue. You seem the SAME features in different organs. It is a DYNAMIC process which evolves over time. The process of inflammation is named ‘itis’
What does inflammation involve?
Changes to BV walls so that leukocytes, fluid and protein can migrate from Bfs into the injured tissue.
What does the outcome and clinical manifestation of inflammation depend on
The nature, intensity, duration of the injurious agent and the tissue effect
What are the triggers to ACUTE inflammation?
Similar triggers to cell injury including
- infections (bacterial, viral, parasitic) and microbial toxins
- trauma (blunt and penetrating)
- Physical and chemical agents (thermal, irradiation)
- Tissue necrosis
- Foreign bodies (splinters, sutures)
- Immune reactions (hypersensitivity)
Outline the process of acute inflammation
- I.e. by necrosis. After injury pro-inflammatory substances are released from the injured cells. These activate resident tissue macrophages and endothelial cells that line the local blood vessels
- Activated endothelial cells produce inflammatory cytokines, prostaglandins and NO that cause vasodilation, increase in blood flow and increase the permeability of blood vessels
- There is increase in blood flow to the tissue (hyperaemia) and increase of protein rich fluid OUT of the vessels into the damaged tissue (exudation). The exudation causes accusation of fluid in the inflamed tissue (oedema)
Loss of fluid from vessels increases blood viscosity so blood velocity slows (stasis). As stasis occurs leukocytes gather at the edges of the blood flow rather than centre -MARGINATION. Leukocytes - mainly neutrophils - gather along vascular endothelium especially at post capillary venules
- Expression of adhesion molecules on luminal surfaces of endothelial cells
- Increased expression of selectin on endothelial cells binds to glycoprotein receptor and slows neutrophils
- Increased expression of integrin on neutrophils which binds to addressins on endothelial cells and stops neutrophils - Neutrophil migration into tissue by diapedesis;
insert cell processes into junctions between endothelial cells and squeeze through into the space between between the endothelial cells and the BASEMENT membrane and eventually into the extra-vascular space. - Neutrophil activation
- neutrophils are activated by chemokines, endothelial cell surface molecules, Interleukin 1 (IL-1), Tumour Necrosis Factor (TNF alpha) which are released by damaged tissue, activated endothelial cells and other leukocytes
- leukocytes in inflamed tissue are activated by bacterial products which bind to Toll Like Receptors
- neutrophils migrate to the injury by moving up a gradient of chemotactic factors (chemotaxis) - Neutrophils attack the inflammation cause
- limited killing potential and many are killed
- necrotic neutrophils release substances that are vasoactive, chemotactic, and damaging to adjacent tissues.
- when infection; tissue debris, bacteria, dead neutrophils make pus
What does the protein exudate leaving the vessels and entering the injured tissue contain?
The fluid exudate contains a number of proteins that play an important role in inflammation - antibodies, fibrinogen, complement proteins, kinin, plasmin cascades which act as chemical mediators
Why is fibrinogen important
Fibrinogen is in the protein exudate that accumulates at injured tissue. It is converted into fibrin which acts as glue to seal damaged blood vessels and stabilises damaged tissues.
Fibrin accumulates on epithelial surfaces such as the pericardium/pleura and is compacted by organ movement into a dense fibrous exudate
What is stasis
The slowing of blood though vessels due to the permeability changes during inflammation causing an increase in permeability of fluid out of the vessels
How do selectin molecules work
Selectin molecules on endothelial luminal surface binds to glycoprotein receptors on the neutrophil like Velcro and cause the neutrophil to slowly roll along the BV
How do interin molecules work
After selectin. Increased expression of selectin molecules on the neutrophils. These bind to ligands called addressins on the endothelial cells so that neutrophils STOP rolling and adhere firmly to the endothelial surface
What is the movement of neutrophils into damaged tissue called
Diapaedesis
What are neutrophils and other leukocytes attracted to/activated by in damaged tissue?
Chemokines, TNF alpha, IL-1, activated endothelial cell surface molecules, and bacterial products that bind to Toll Like Receptors
What are chemotactic factors and what do they bind to?
Can be…
Exogenous substances: bacterial products with an N-formyl-methionine terminal amino acid
Endogenous - components of the complement system and chemokines (IL-8 and C5a)
Most chemokines bind to 7 transmembrane G-protein coupled receptors on the leukocyte surface which will increase actin polymerisation at the leading edge of the cell and cause extension of FILOPPDIA (cell processes) towards to injury site
When does acute inflammation subside?
When the offending agent is terminated and secreted mediators of inflammation are broken down. There are anti-inflammatory mechanisms to control the response and prevent it causing excessive damage to the tissue.
What are the gate keepers of acute inflammation?
Endothelial cells. Result in a range of molecular signals being activated. When sitting above an injured tissue they turn on a new gene transcription leading to the production of inflammatory molecules
