Acute Inflammation 1- Events and Mechanisms Flashcards
What is acute inflammation?
The process by which cells and exudate accumulate in irritated tissues and usually tend to protect from further injury. It is a rapid and protective mechanism to protect tissue
What is exudate?
A protein-rich fluid that arrives due to an increase in vascular permeability and contains antibodies and proteins which fight infection
What are the two types of inflammation?
- Acute:
Rapid and protective mechanism to protect tissue - Chronic:
Recurring inflammation
What are the four cardinal signs?
- Heat
- Redness
- Swelling
- Pain
What is orbital cellulitis?
A diffuse inflammation of subcutaneous tissues, which spreads along the connective tissue planes, caused by a bacteria and resulting in acute inflammation
What are the main processes of inflammation?
Vasodilation and increased permeability (allows protein-rich fluid to accumulate)
What are the causes of inflammation?
- Chemical sources (acid, alkali, histamine etc.)
- Hypoxia (inadequate oxygen supply leading to release of Hypoxia-Inducible Factor-1 (HIF-1), and/or necrosis with the release of uric acid and ATP from cells)
- Infective agent (e.g. bacterial, viral, fungal, parasitic, rikettsial, mycoplasmic, protozoal)
- Nutritional abnormality (e.g. niacin deficiency leading to pellagra)
- Physical trauma (e.g. heat, trauma, cold, radiation)
- Immunological sources (e.g. excessive response to exogenous antigen (allergy), autoimmunity)
- Genetic abnormality (e.g. HGPRTase deficiency leading to gout)
In simple terms. describe the mechanisms of inflammation
- A change in the vessels
- Dilate and enlarge to increase blood flow in inflamed tissue (redness/heat)
- Increased permeability (swelling/pain from stretch on inflamed tissue) - Swelling and exudation
- Gaps open up to allow protein-rich plasma to exude from blood vessel into inflamed tissue
- Leukocytes then emigrate from vessel to enter inflamed tissue to fight infection
What are the characteristics of an acutely inflamed tissue?
- Blood vessel has dilated and is full of RBCs, due to increase blood flow in tissue
- Lots of clear space, due to exudation of clear fluid into tissue
Elaborate on swelling and exudation in the inflammatory response
Increased permeability in the microvasculature
- Primarily in venules- histamine induced contraction by endothelial cells
- Gaps open up in endothelial cells by chemicals
- Histamine (released from granules in mast cells) has receptors on endothelial cells of venules which cause them to contract and open up venule when required - Severe irritant can lead to apoptosis or necrosis
- Damage to endothelial cells, which causes leakage - Results in proteinaceous exudate
- Eventually leads to stasis (can leads to ischemia and allows leukocytes to slow down and enter tissue)
What are the primary benefits of exudate?
- Dilution of irritant
- Extravasation of plasma proteins
* Immunoglobulins/ antibodies-can fight microbe
* Complement (recruitment of leukocytes, opsonisation, perforation of pathogen cell membranes)
* Coagulation proteins including fibrinogen, which can form insoluble fibrin to wall off irritant (see more information below) - Nutrition is provided for tissue cells and leucocytes
What is Fibrinous exudate?
Exudate where fibrinogen is coagulated to fibrin, which is an adherent protein
How do you recognise fibrin from collagen microscopically?
Fibrin is laid down haphazardly whereas collagen is laid down in parallel bundles
What are the harmful effects of exudation?
- Swelling:
- Pain due to stretching of the tissue
- If the epiglottis where to clog it would compromise oxygen intake
- In the bone, it could cause ischaemia (lack of blood flow)
- Meninges can lead to intracranial pressure - Microbes causing inflammation may be spread by exudate
- Stasis can lead to impaired blood flow, and endothelial injury may lead to thrombosis and ischaemia, or necrosis of tissue.
Cellular emigration can be used to refer to when white-blood cells emigrate from the blood to the infected tissue. Elaborate on the types, and their purpose
- Neutrophils (PMN) have multi-lobed nuclei, and are usually 10um in diameter. They predominate early in acute inflammation.
- Lymphocytes play a role in acute inflammation caused by intracellular microorganisms eg/ viruses. They are 8-10um in diameter, and have an oval nucleus with little cytoplasm
- Monocytes (which mature into macrophages) are around 20um in diameter, and have a kidney shaped nucleus with abundant cytoplasm. They play a major role in the later stages as well as in chronic inflammation and healing.
What is margination?
The process in which leukocytes move to the periphery of the vessels due to changes in the haemodynamic conditions (increased vessel diameter and also stasis)
What is pavementing and diapedesis?
Pavementing: when neutrophils cover the endothelium of the blood vessel as they adhere to the side
Diapedesis: when neutrophils leave the blood capillaries and enter tissue
What is chemotaxis?
The direction movement of cells along a chemical gradient (to the site of injury)
The emigration of WBCs occurs via the projection of a pseudopod between the blood vessel’s endothelial cell
After penetrating the vascular basement membrane by enzymatic digestions, WBCs move to the site of greatest concentration of chemotactic factors using acting filaments in the cytoplasm.
Do neutrophils or monocytes dominate early in inflammation?
Neutrophils tend to dominate early (6-24 hours) as they are more numerous than monocytes, they respond more rapidly to chemokines and they attach more firmly to adhesive molecules induced upon the endothelium. But undergo apoptosis after 12-24 hours.
Hence monocytes tend to dominate later in the inflammatory response (longer lived, can proliferate in tissue), unless there is continued recruitment of neutrophils
What are some common chemotactic molecules?’
Let there be four In lave to eat, and then C4, nah C5 aye?
o Endogenous chemicals -LTB4 -IL-8 -C5a o Exogenous chemicals -N-formylated bacterial peptides (bacteria with this peptide are strongly chemoattractive for neutrophils, and are refered to as pyogenic meaning pus-inducing -Some lipids that are bacterial products
What is the morphology of exudate dependent upon?
- DOSAGE
The nature and dose of the irritant- a small dose may lead to watery’serous exudate, whereas a large dose may lead to Fibrinous exudate - TISSUE
The organ or tissue involved- mesothelial cells more likely to form fibrinous exudate - RESPONSE
The nature of the host response- different irritants will cause different responses
What are the types of exudate?
- Serous- a water exudate
- Mucous- a development of serous exudate
- Fibrinous- White, stringy fibrin forming
- Purulent/suppuratives- containing pus
- Pseudomembranous- formation of a false membrane
- Ulcer- Serious case of exudation damage to epithelial surface
- Haemorrhage- Damage to vessels from exudation
THERE CAN BE A COMBINATION OF THESE DIFFERENT TYPES!
Describe the process of phagocytosis by leucocytes
- Opsonisation (helping to recognise) where apsonins (condiments) including IgG and the complement C3b are recognise by WBC receptors. This is a process done by the complement system
- Phagocytosis (Engulfment)
where foreign particles are engulfed by the extension of cytoplasmic pseuodpods, which enclose the particle in a membrane bound phagosome (vesicle) - Killing (Degradation) where the phagosome fuses with a lysosomal granule to form a phagolysosome, where the foreign organism is killed or degraded by the digestive enzymes and oxygen radicals in the lysosome
