Flashcards in Inflammation and Repair Deck (45):
What causes inflammation?
Infections, necrosis, foreign bodies (rate crystals from GOUT, cholesterol crystals, and lipids) and immune reactions.
When rate crystals are consumed they cause damage to the membrane of the phagolysosome leading to release of lysosomal enzymes.
Recognition of microbes is done by...
TLR (toll like receptors)
What are some molecules that indicate cell damage.
Uric acid; DNA break down
Increased ATP; mitochondria break down
Reduced K concentration; plasma membrane damage
DNA in the cytoplasm.
These molecules cause activation of the inflammasome, which causes production of IL-1
cause fever indirectly
A gain of function of the inflammasome will cause...
auto inflammatory syndromes
Acute inflammation major components
Dilation of small vessels, which increases blood flow
Increased permeability, which allows for proteins and leukocytes to leave vessel.
Emigration of leukocytes to activation and elimination of microbes.
Key sign of acute inflammation is the presence of neutrophils
Effects of histamine and serotonin
Main regulator of blood dilation in brain is via serotonin, while histamine effects the whole body.
Histamine cause stasis to develop, which allow for transmigration of leukocytes out of BV.
Release of histamine is regulated by
physical damage, binding of ab to mast cells, hypersensitivity, and anaphylatoxins.
What is exudation? vs ultra filtrate
It is the escape of fluid proteins and leukocytes from vascular tissue into tissue.
Ultra filtrate is considered transudate, which is low protein content with little or no cellular material.
Pus, which is an exudate rich in leukocytes (neutrophils mainly), debris, and microbes.
What are the binding factors/factors for transmigration of leukocytes
Sialyl-lewis X (rolling), CD18/31 (stoping), secretion of collegenase (extravasation).
What are the binding factors of endothelium cells for transmigration of leukocytes
P and E selectins (rolling), ICAM-1 and VCAM-1, used for stoping
Leukocyte adhesion deficiency
The patient will have recurrent bacterial infections, due to defective inflammation process.
IL-8, C5a, C3a, C4a, and leukotriene B4 (LTB4)
They work by activating GPCR and causing polymerization of actin filaments in direction of concentration.
What do corticosteroids do to the inflammation process?
They inhibit the formation of AA by preventing the activation of PLA-2. This prevents the formation of COX products such as PGE-2 (fever), indirectly decreasing IL-1 and TNF formation, also decreasing iNOS formation.
Causes vasodilation and increase permeability of capillary, edema formation, chemo attractant for neutrophils, and causes fever
Causes vasodilation and increases the permeability of capillary, causes edema formation in neutrophils.
contraction of uterine, bronchial smooth muscles, and small arterioles.
Potent inhibitor of platelet aggregation and vasodilator
Potent platelet aggregator and vasoconstrictor.
Used for protection of gastric mucosa
potent chemotactic agent for neutrophils and causes generation of ROS and release of lysosomal granules.
LT C4, D4, and E4
cause vasoconstriction, bronchospasm, and increased permeability of venues and causing bronchospasm.
Used to suppress inflammation by inhibiting the recruitment of leukocytes by inhibiting chemotaxis and adhesion to endothelium.
ROS formed for break down of microbes
Respiratory burst causes the formation of supra-oxide via NADPH oxidase
Dismutase then converts supra-oxide into H2O2
Myeloperoxidase (MPO) then converts hydrogen peroxide into bleach.
Secondary Granule content
Lysozymes, collagenase, gelatinase, lactoferrin, plasminogen activator, hisaminase, and alkaline phosphate.
Primary granule content
Myeloperoxidase, bacterial factors (lysozymes and defensins), acid hydrolase, and a variety of neutral proteases (cleaves extracellular components and C3 and C5 proteins).
NETs (neutrophils extracellular traps)
Extracellular fibrillar network that provides antimicrobial substances, which prevents the spread of microbes by trapping them in fibrils.
Caseating granuoma and shows signs of giant cells.
Acid-fast bacilli in macrophages; non-caseating granulomas.
Gumma: plasma cell infiltrate, central cells are are necrotic.
Rounded stellate granuloma containing central granular debris and recognizable neutrophils,
Non-caseating granulomas with abundant activated macrophages
Crowns disease (inflammatory bowel disease)
Non-caseating granulomas in the wall of the intestine.
Systemic effects of inflammation
Fever (PGE-2), acute phase proteins (CRP,SSA), increased leukocytes, high levels of IL-1 and TNF.
Steps of scar formation
Granulation tissue formation (fibroblast/connective tissue)
Remodeling connective tissue: remodeling of connective tissue, making scar.
Scar contraction (myofibroblasts)
What converts collagen type 3 into collagen type 1 in scars.
Matrix metalloproteinase (MMP's), requires zinc to function
Factors that effect tissue repair
Diabetes (abnormal wound healing)
Nutritional status (Vit C)
Glucocorticoids (steroids, inhibits PLA-2)
Type of injury and extent of injury
Location of injury
What does CSF (colony stimulating factor) do?
CSF is responsible for proliferation of progenitor cells in the bone marrow and hematopoietic stem cells.
Liver regeneration phases (3)
Priming phase (IL-6, induce GF receptors)
Growth factor phase (HGF and TGF-a, cell cycle stimulation)
Termination phase (restoration to quiescence TGF-B)
Healing by First intension
This is only if the damage is on the epithelial layer. Epithelial regeneration and happens if the cut is small and there are few epithelial deaths.
This process takes about a month to fully repair and form scar tissue that contain fibrous unions. This causes tensile strength of the wound to increase.
Healing by Second intension
This is if the damage goes beneath the epidermis. This is generally done for large wounds,abscess, ulcerations, and ischemic necrosis.
This process involves the conversation of collagen type 3 to collagen type 1 (2 weeks)
Wound contracture happens here so the scar that is formed is much smaller (5-10% of original size)
When does an organ go through fibrosis?
When an organ receives repeated injury such as drinking alcohol, it will recruit macrophages, which will cause destruction of tissue and replacement with fibroblasts, thus making it hard and there is a loss of function.
What is a keloid?
Keloids are tissues that have collagen type 3 in excess. This happens because the collagen type is suppose to be converted to type 1, but something happens so the scar grows beyond the area of injury.