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161 Cards in this Set

  • Front
  • Back
causes of cell injury
physical agents
chemical agents
nutritional
infectious disease
immunological mechanisms
effects of cell injury depends on:
severity , duration of injurty
vulnerability of the cell
cell's metobalic rate
-cells can adapt with structural and metabolic changes
Cell membrane systems that are vulnerables
-cell membrane
-aerobic respiration, mitochondria
-protein synthesis
-genetic apparatus integrity , DNA
common biochemical themes in cell injury
-ATP depletion due to loss of oxidative phosphorylation in the mitochondria
-loss of calciumhomeostasis
-reactive oxeygon species
what happens in ATP depletion
Na accumulates intracellularly
K diffuses out of cell
Ca moves intracellularly
water and ion diffuse into cell
cellular swelling
what happens in loss of calcium homeostasis
-normally intracellular cytosolic calcium concentrations are lower than extracellular calcium and mitochondrial or ER Ca
-this is maintained by ATP dependent calcium transporter
-Ca influx due to energy failure will activate calcium dependent degradative enzymes
what happens with reactive oxygen species and protective factors
-hydrogen peroxide
-superoxide anion
-hydroxyl radicals

protective factors are:
-superoxide dismutase
-glutathione peroxidase
-catalase
Reversible subcellular changes occurring in reversibly injured cells
-cellular swelling vacuoles formation
-blebbing of plasma membrane
-swelling of mitochondria
-dilation of ER
-Fatty changes
Reversible subcellular changes morphological features
increased pallor
increased turgor
increased weight
Irreversible Injury
-cell unable to produce ATP
-membrane is severely damaged
-point of no return
morphological changes in irreversible cell injury
disruption of plasma membrane, which is why cardiac and liver enzymes are measured in blood to assess myocardial infarction and liver cell injury

nulcear changes, including pyknosis, karyoohexis, karyolysis

rupture of lysosomes, release of lysosomal enzymes
sublethal stress causes the cell to adapt by:
atrophy-shrinkage; occurs in skeletal muscles, heart, secondary sex organs and brain.
hypertrophy-increase in size of cells; common in heart, increased synthesis of extracellular proteins, physiologic, pathologic
hyperplasia-increase in number of cells. can occur with hypertrophy; cannot happen in nerve, cardiac, skeletal , mediated by growth factors and increased DNA division.
metaplasia- reversible replacement of one mature cell by another which is better able to tolerate stress
dysplasia- not a true adaptive change, abnormal proliferation, changes in size shape and organization, atypical hyperplasia, occurs in cervix
cellular accumulation
Atrophy
-reduced functional demand
-inadequate supply of oxygen; myocardial muscles around ischemic areas
-interruption of trophic hormonal signals; menopausal decrease in estrogen and myometrial changes
-persistent cell injury; atrophy of gastric mucosa in chronic gastritis
Hyperplasia
-hormonal stimulation: glandular hyperplasia during breast feeding due to estrogen
Erythropoietin stimulates RBC production normally secreted from kidney, renal tumors and result in bone marrow hyperplasia

-Increased functional demand: bone marrow hyperplasia at high atltitude
-anigenic stimulation in lymphoid hyperplasia in immune responsiveness
Metaplasia
bronchial lining: columnar epi becomes squamous epi in smokers

-acid reflux: normal squamous becomes columnar
Intracellular accumulation
-fat in alcoholic liver injury
-glycogen in inherited lysosomal storage disease
-abnormal proteins: lipofuscin
-iron: hemosiderosis
lipofuscin
wear and tear pigment
-by product of lipid peroxidation-
-non toxic
-resist digestion and persist as membrane bound residual bodies
Hemosiderosis
-denatures form of ferritin
-25% of iron is stored in form of ferritin in hemosiderin
-found in areas of hemmorage or bruises
-normally spleen, bone marrow, and liver
-in frequent blood transfusion
-iron is present throughout body, in places like skin, pancreas, heart, and kidney
Cholesterol
-muscle layer of heart blood vessel is filled with foam cells with lipid vacoules
Calcification
Can be dystrophic:
occurs in dead or injured cells
-blood calcium level is normal
-leads to crystal formation
-appears as white, gritty, granule
-microscopic appearance: deep purple deposits in necrotic tissues
Metastatic Calcification
-occurs in living cells
-hypercalcemic states
- associated with increase serum calcium concentration
-happens in renal failure, nephrocalcinosis, and depositsin kidney

-caused by: vitamin D intoxication, multiple myleoma, parathyroid hormone, hyperparathyroidism, pagets disease
Hyaline changes
-alteration that appears pink
-alchoholic hyaline
- amyloid
The appearance of dead cells is the result of:
-enzymatic digestion; can be secreted by white blood cells or by dying cells that destroy cells of organ
-protein denaturaton: they are injured secondary to cell injury, bind to stain and appear pink
Necrosis
-progressive enzymatic degradation

-always invokes an inflammatory response, our immune cells migrate to the area of dead cells
-proteins denature, appears pink, loss of glycogen particles makes it appear glassy
-pyknosis, karyolysis
Patterns of necrosis
-coagulative
-liquifactive
-gangrenous
-caseous
-fat necrosis
-fibrinoid
coagulative necrosis
-due to denaturation of cellular proteins
-tissue appears as a solic mass, ghosted cell outline, loss of cell structure
-structural outline of cell is preserved
-tissues have firm texture
-myocardial infarction
-heart,kidney,liver,solid organs
-ischemic injury
Gangrenous necrosis
-coagulative necrosis
-ishemic etiology
-peripheral vascular disease, limbs primarily affected
-occurs in lower extremetiies
-wet involves bacteria causing liquifactive necrosis
-dry gangrene involves microscopic pattern of coagulation necrosis
Liquifactive necrosis
-result from tissue digestion by phagocytes hydrolytic enzymes
-occurs in abcess, brain infarcts
-in the CNS, infarction results in liquefactive necrosis
-not complete loss of cellular archetecture
Caseous necrosis
-combination of coagulative and liquifactive
-caseous necrosis in tuberculosis infection
-associated with granuloma formation
-tissue architecture is completley destroyed
Fat necrosis
-occur as a result of pancreatic lipase
-produces focal areas of destruction of fat tissue surrounding pancreas
-released fatty acids combine with calcium to produce fat saponification
Fibrinoid Necrosis
- Occurs in blood vessel
-histologically resemble fibrin
-associated with immunological injury
-fibrin plasma leaks out of blood vessel
-wall of blood vessel becomes pink stained
Apoptosis
-cellular suicide
-orchestrated sequential death
-includes protein cleavage by a group of enzymes known as capsases, protein cross linking, DNA breakdown
-requires genetic activation and regulated by genes
-if affects single cells
-no inflammatory response
-capsases digest nuclear and cytoplasmic proteins
-capsases activates endonucleases
Genes apoptosis is regulated by:
-Bcl-2: inhibits apoptosis
-P53: stimulates apoptosis
Apoptosis steps
-abnormal mitochondrial membran permeability is crucial event which;
-allows escape of cytochorme C into cytosol which
-activates proteolytic enzymes, capsases, leading to execution of process
-final phase is removal of dead cell fragments by phagocytosis without inflammatory response
morphological changes in apoptosis
-cell shrinkage
-chromatin condensation with peripheral clumping
-surface blebs
-fragmentation into apoptic bodies
-ingestion by macrophages
examples of apoptosis
implantation, organogensisis
-menstrual cycle
-deletion of autoreactive T cells in the thymus
-pathologic examples occur in viral hepatits, single liver cells, infected with viruses undergo this
apoptosis vs. necrosis
-necrosis has cell swelling, random nuclear fragmentation, inflammation
-apoptosis has cell shrinkage, specific DNA fragmentation, no inflammation
INFLAMMATION
functions to
-eliminate insult
-remove dead cells
-allow tissue repair to take place
acute inflammation
minutes/days

neutrophils

increased permeability with exudation of luids and plasma proteins
chronic inflammation
days/years

macrophages/lymphocytes

proliferation of blood vessels

fibrosis and tissue necrosis
players of inflammatory response
- inflammatory cells
-cells lining blood vessels
-cells in extracellular matrix

-chemical mediators

-blood vessels
pathology of inflammation
-exaggerated: hypersensitivity
-inappropriate: autoimmune
-deficient: immune deficiency
inflammation produces localized symptoms such as:
tumour
rubor
calor
dolor
loss of function
sequence of acute inflammation
-residential phagocytic cells recognize the offending agent

-secrete mediators to recruit other immune cells

-mediators act on blood vessels
vascular events in acute inflammation
-initial transient vasoconstriction

-massive arteriolar vasodilation, result in increased blood flow; erythema and warmth

-increased vascular permeability will result in swelling

-increased engorgment of blood vessels will result in slowing of blood flow
vascular events in acute inflammation: hyperemia
-increased blood flow
-due to vasodilation of the precapillary arterioles

-redness and heat

-mediated by histamine, bradykinin, and prostglandins
vascular events in acute inflammation:increased permeability
-increased blood flow initially results in increased hydrostatic pressure, the fluid is a transudate

-later, vessel permeability increases, the fluid is exudate

-proteins are lost into the interstitial space

- swelling
there are two types of fluid leaving the intravascular compartment into the interstitial space
transudate: low protein fluid, and ultrafiltrate of plasma

exudate: high protein fluid, increased permeability to protein molecules
In inflammation the fluid is exudate and it is caused by:
leakage of proteins:
albumin

globulins

fibrinogens (only if blood vessel is severely damaged)
constituents of the inflammatory exudate
-consists of erythrocytes that have leaked out of the very permeable and congested capillaries

-thin strands of fibrin derived from fibrinogen in the exuded plasma

- leukocytes that have exited the vessels via transmigration
the lymphatic response
-during inflammation,the whole inflammatory exudate is removed by the lymphatics

-lymphatic vessels become secondarily inflamed; lymphangitis

-draining of lymph nodes is lymphadenitis

-lymph nodes show reactive hyperplasia
cellular events in acute inflammation
-leukocytes are the mjor cellular components of the inflammatory response: they include polymorphonuclear cells, eosinophils, lymphocytes, but the main are PMN's

-the leukocytes become activated
leukocyte recruitment into the area of inflammation involves the following steps
-margination-rolling=adhesion

-transmigration:mediated by PECAM-1

-chemotaxis: once outside the blood vessels, inflammatory cells migrate by chemotaxis

-phagocytosis: recognize particles by opsonins, phagocytose into the phagosome, digest the particle in the phagolysosome.
chemotaxis: important chemotactic factors
-bacterial products
-leukotriene B4
-C5a
-IL-8
leukocyte activation:
will be able to move, produce mediators, produce ROS, and phagocytose
-microbes
-cytokines
-chemokines
-lipid mediators
Opsonins
-to help in the process of phagocytosis

-IgG
-C3b
-collectins

receptors on white blood cell for opsonins
phagocytosis and killing
- killing by oxeygon species

O2, H2O2, HOCL

-myeloperoxidase coverts h2O2 to HOCL
killing and degradation via non oxidative bacterial killing
-lysosomal hydrolases

-bactericidal permeability protein

-lysozyme

-major basic protein

-defensin
Neutrophills life span
6-24 hours, so they are replaced by monocytes in a day or two
pathological sequence of inflammatory response
-TB
-reperfusion injury after myocardial infarction

-autoimmune disease

-allergy
Possible outcomes of ACUTE inflammation
-resolution

-fibrosis

-chronic inflammation
Acute inflammation: resolution
-complete resotration

-minimal cell death and damage
-damaged tissue can be replaced
Acute inflammation: progression to chronic inflammation
-injury persists
-tissue damage continues
-macrophage are called upon to replace neurtophils
-begin chronic inflammation
Acute inflammation: fibrosis and scarring
- if resolution fails

-excessive damage

-the fibrinous exudate persist, the fibrinin stimulate the fibroblast and blood vessel formation to form scar tissue.
Acute inflammation: abscess formation
-formation of pus

-where pus accumulates and becomes localized forming abscess

-caused by pyogenic bacteria
diseases of defective phagocytic functions
-leukocyte adhesion deficiency: defective integrin expression

-chediak-higashi syndrome: defective lysosomal granules

-chronic granulomatous diseases: no ROS is produced
acquired defects in phagocytic functions
- diabetes
-leukemia
-malnutrition
-sepsis
-cancer
-chemotherapy
inflammatory response: mediators
-cellular: from metabolism of arachidonic acid and phospholipids. Cytokines from inflammatory cells

-plasma:from coagulation cascade, from kinin generation, from complement system
Plasma derived mediators from coagulation cascade
-thrombin
-factor Xa
-fibrinopeptides
plasma derived mediators from kinin system
-bradykinin: increased vascular permeability, pain, vasodilation
plasma derived mediators from complement system
-c5a and C3a chemotaxis and anaphylatoxins

-C3b opsonin

-c5-C9 membrane attack complex
Cell derived mediators
-arachadonic acid metabolites: prostaglandins, leukotrienes, lipoxins

-cytokines: TNF and IL-1

-chemokines
most important cytokines in acute inflammation are:
TNF

IL-1
systemic manifestation of inflammation (SIRS)
-fever
-leukocytosis
-leukopenia
-acute phase response
Fever
-mediated by IL-1 TNF

-prostglandins produced from arachidonic acid

-NSAID block prostglandin synthesis
Differential WBC count can reveal
-neutrophillia: bacterial infection

-eosinophillia: parasitic infection or allergic

-lymphocytosis: viral infection

- leukopenia: typhoid fever
Acute phase reaction : secretion of acute phase proteins
- C reactive proteins
-fibrinogen
-serum amyloid A
basic microscopic appearance of morphology of acute inflammation
-edematous
-blood vessel dilation
-inflammatory cell infiltration
gross patterns of acute inflammation morphology
-serous
-fibrinous
-suppurative -abscess
-ulcer
Serous inflammation
-exudate is water and p rotein poor
-blister for example
-occurs into a serous body cavity it is called effusion
fibrinous inflammation
-exudate has large molecule proteins, fibrinogen

-appears as pink, eosinophillic mesh

-pericarditis, pleuritis, meningitis
suppurative inflammation
-large amount of exudate
-purulent exudate: pus, celular debris and inflammatory cells
-bacteria
-abscess
Ulcer
-erosion of mucosal surface

-occurs in : surface mucosa of gut, lower limbs when blood supply is interrupted
chronic inflammation
-prolonged duration
-active process
-tissue destruction
-simultaneously with healing process
primary causes of chronic inflammation
-persistent infection acute to chronic

-recurrent acute inflammation, acute on chronic

-chronic from onset
examples of chronic inflammatory conditions
-TB
-leprosy
-Rheumatoid arthritis
-inflammatory bowel disease
-atheroscelrosis
-silicosis
Chronic inflammation: cellular events
-they undergo recruitment and migration

-macrophages
-lymphocytes
-plasma cells
-eosinophils
Chronic inflammation: macrophages
-derived from blood monocytes
-tissue based: Histiocyte (spleen), kuppfer (liver), osteoclasts (bone) microglia( CNS)
-secretes cytokines
-undergo chemotaxis
-activated into epitheloid cells
-fuse into giant cells
Chronic inflammation: lymphocytes
- B cells and plasma cells
-t lymphocytes
-produce IFN-y
chronic inflammation: macrophages and lymphocyte interaction
-produce mediators of chronic inflammation

-amplify and prolong the chronic inflammatory reaction

-IFN-y and IL-1
chronic inflammation: eosinophils
-secretes eotaxin and major basic protein MBP
-important in parastic infections
chronic inflammation is characterized by:
-chronic inflammatory cells infiltration
-blood vessels proliferation

-tissue destruction

-fibrous tissue formation
chronic granulomatous inflammation
-chronic inflammation can be diffuse or granulomatous

-granulomatous: localized collection of chronic inflammatory cells
-may or may not have central area of caseous necrosis
Granuloma
-central area of: macrophages, epitheloid cells, multinucleated cells

-surrounded in periphery by: lymphocytes and plasma cells

-an outer rim of fibroblasts and connective tissue
granulomatous inflammatory conditions
-TB
-leprosy
-sarcoidosis
-syphilis
-fungal infection
-parastic infection
-foreign bodies
-cat scratch fever
Tissue repair : two ways
-regeneration

-fibrosis and scar formation
cell proliferation: how are new cells formed and how is the process regulated
-mainly driven by growth factors

-growth factors promote entry of cells into the cell cylcle
cell cycle
-G1- presynthetic grwoth phase

-S-DNA synthesis

-G2- premitotic growth phase

-M-mitotic phase
Labile cells
-replaced by maturation from stem cells and by proliferation of mature cells


-Mature cells continuously enter the cell cycle

-bone marrow cells and epi cells
Stable cells
- quiescent ( in the GO stage of the cell cycle

-have only minimal replicative activity in their normal state

-capable of proliferation response to injury or loss of tissue mass

-liver (unlimited capacity) and kidney (limited capacity)
permanent cells
-terminally differentiated and non proliferative in postnatal life

-neurons and myocardial cells
growth factors
-inititiate entry of cells into the cell cycle and promote their transition from GO to G1


-Moving from one phase of cell cycle to another is controlled by cyclins
How do growth factor initiate the process of proliferation
-bind to a receptor

-trigger event

-signal is transduced into the cell

-associate with the DNA

-activate transcription factor
How growth factors send their signals in tissue repair
-autocrine

-paracrine
Growth factors
EGF
TFG-a
HGF
PDGF
FGF
KGF\


KNOW PRIMARY SOURCE AND PRIMARY ROLE IN REGENERATION
where do growth factors come from
-white blood cells
-endothelium

-other inflammatory cells
what is the role of the ECM surrounding the proliferation cells
-provides support to proliferating cells

-storage and presentation of growth factors

-scaffolding for tissue renewal

-cells migrate through ECM, and adhere ECM components
repair by regeneration
-renewal of a damaged tissue by tissues identical to the original one

-tissues are derived from small number of embryonic or adult stem cells

-have potential to replenish and regenerate
repair by connective tissue
-fibrosis and scare formation

-occurs in permanent cells

-or when tissue damage is severe
steps of repair by connective tissue
-angiogenisis
-migration and proliferation of fibroblasts fibrosis

-deposition of ECM
-remodeling
Angiogensis
-sprouting of existing blood vessels

-formation of new blood vessels by implanting endothelial precursors stem cells from bone marrow
migration of fibroblasts in repair of connective tissue
-migrate to area of repair

-macrophages clear the area and induce proliferation of fibroblasts

-fibroblasts deposit ECM into the area of repair

-growth factors involved: TGF-b, PDGF, FGF
results from angiogensis and migration of fibroblasts
- formation of granulation tissue
organ repair

-loose connective tissue
Scar formation.. after angiogenisis and fibroblast migration
-fibroblast proliferation decreases

-new blood vessel formation decreases

-synthesis of collagen increases

-the collagen in the scare is fibrillar collagen

-synthesis begins in 3-5 days

-attains max tensile strenght with cross linking and in presence of vit. C
scar remodling .. step four
-removal of excess collagen
-accomplished by collagenase enzymes

-matrix metalloproteiease MMP
the outcome of the process of repair depends on the balance between....
-collagen and other ECM syntehsis

-degradation
collagen degradation
-metalloproteinease enzymes
-highly regulated
-exist in inactive form
-require zinc for activation
repair in skin cutaneous membrane: three steps
1-inflammation: clot formation and Acute inflammatory response

2-Formation of granulation tissue: fibroblast migration and proliferation and new blood vessel formation

3-ECM deposition and remodling; collagen synthesis and deposition, collagen degradation
types of skin wound healing
-healing by first intention
-healing by second intention
healing by first intention
-uninfected
-surgical incision, borders are proximate to each other
-adequate blood supply
-minimal tissue destruction
-minimal contracture
healing with first intention:within a day(step one)
1-thrombosis: formed from plasma fibrin

forms barrier to invading microorgansisms
repair in skin: first intention (step two)
2-inflammation: dead cells and microorganisms must be removed

-neurtophils liquefies the necrotic tissue

-macrophages phagocytose cellular debris and signals repair

-24-48 hours

-reepithelization
-labile cells regenerate
healing with first intention: granulation tissue (step four)
-day 3
-transient , specialized organ of repair

-replaces provisional matrix, collagen: vertical fibers

-cells (macrophages) and proliferating capillaries

-thin epithelium
cells of granulation tissue for repair in skin
fibroblasts
myofibroblasts
macrophages
first intention healing: step five ; repair in skin

proliferating blood vessels
-angiogensis
-sprouting of endo cells
-horizontal collagen fibers
-thick epi
repair in skin: granulation tissue
-vascular
-edematous: leaky new endo
-insensitive: nerves in dermis destroyed

-site where extracellular matrix will be deposited
fibroblasts proliferation and matrix accumulation: first intention; second week
- collagen accumulation
-inflammation decrease
-less edema
-less blood vessels
-less inflammatory cells
Scar formation : first month; first intention
-avascular
-completely covered by epidermis
-non inflammatory
-lacks hair and nerve supply
healing by second intention occurs in:
-extensive tissue destruction
-ulcer
-burns
-abscesses

characterized by: marked inflammatory response, wound contracture, excessive granulation tissue formation
wound contracture
-specialized cell of granulation tissue

-myofibroblast, a modified fibroblast

-they have the ability to contract

-appear in the third day

-present in burn scars
Wound strength:second intention
-rapid increase in the tensile strength at 7 to 14 days

-but is is only 10-20 percent of the ultimate strength

-most of the strength results results from the cross linking of type I collagen and collagen synthesis exceeding collagen degradation

-70 percent of the strength is reached after three months
conditions that modify repair
-location of the wound
-blood supply
-coagulation defects
-infection
-nutrition
-presence of foreign body
-diseases: DM and atheroscelrosis
repair patterns in specific sites
TISSUE SPACES
-pleural, pericardiial and peritoneal cavities

-characterized by large amount of inflammatory exudates

-repair may be achieved by : resolution if there is no extensive cell death occurring the exudates is completely removed and the tissue return to normal

-Repair may also be achieved by organization If:
-there is extensive exudate accumulation
-granulation tissue grow into the exudate
-the exudate is transformed into fibrous tissue
Kidney
-kidney is composed ot fubules and glomeruli
-tubular epithelium regenerates
-regeneration is non existent in glomeruli
-glomeruli heal by fibrosis
Lung
-superficial injury to respiratory epi heal by regeneration

-alveolar air sac injury with intact basement membrane heal by regeneration: infection, shock

-alveolar injury with disrupted basement membrane heal by fibrosis
Heart
-myocardial cells are non dividing terminally differentiated permanent cells

-infarcted muscle are replaced by granulation tissue initially and later by scar tissue
suboptimal wound repair
-wound dehiscence
-trophic ulcers
-keloid
-excessive contracture
wound dehiscence
-after abdominal surgery
-increased mechanical sress on wound
-wound split open and pull apart
trophic ulcer: non healing wounds in areas
-inadequate blood dupply
-devoid of sensation
-leprosy, diabetic peripheral neuropathy
wound contracture
-excessive myofibroblasts contracture

-locations: palm, sole and anterior thorax
keloid
-excessive scar formation that extends beyond the site of injury
-common among dark skin individuals
-irregular collagen and more abundant fibroblasts
inflammatory mediators.. IgE
-amines
-eicosanoids
-cytokines
Two vasoactive amines
-histamine
-seratonin
Eicosanoids
-prostaglandin
-thromboxane
-leukotriene
principle cell derived mediators of inflammation
-eicosanoids
eicosanoids
-inflammatory response, pain, fever
-coagulation
-GI protection
-pulmonary embolism
-thrombosis is the cause of most heart attacks and strokes
Eicosanoids
-derived from oxygenation of 20 carbon essential fatty acids, omega 3 and 6

-prostglandin, thromboxane, leukotriene, (PG< TX, LT)

-most common precursor arachidonic acid; four double bond
Eisosanoid metabolism
-corticosteriods inhibits the production of arachidonic acid by inhibiting PIP2a

-NSAIDS inhibit eicosanoid metabolism by inhibiting COX functions producing PGG2
Three major groups of eicosanoids
-leukotrienes
-thromboxanes
-prostglandins
pathways for arachodonic acid
-COX converts A acid to PGG2

-Liposygenase converts A acid to leukotrienes

-aspirin inhibits COX , inhibiting the production of prostglandins and thromboxanes
PGI2- prostacyclin
-produced by vascular endothelial cells
-inhibits platelet aggregation
-causes vasodilation
Thromboxane: TXA2
-produced by plateleets
-stimulates platelet aggregation
-causes vasoconstriction
Leukotriens and asthma
-SRS-a: slow reacting substance of anaplylaxis

-starts with glutathione
-LTC4 converts it to glutamate,
-LTD4 converts glutamate to glycine, which leaves LTE4
inflammatory mediators in Asthma
-SRS- A (C4,D4,E4)
-prostaglandin D2
-histamine
-acetylcholline
-platelet activing factor
Aspirin induced asthma
-it knocks out COX
-without cox, all A-acid is shifted toward the leukotrienes production via lipoxygenase
Prostaglandins and GI
-most activate motility

-PGE, gastric protectors
Aspirin is an irreversible inhibitor
-it acetylates COX, leaving salicyclic acid behind from aspirin
COX I
- constituitive
-widely distributed
-gastric protection
COX II
-inducible
-inflammatory cells
Diet can modulate PG metabolism
omega 3 diet will be less inflammatory than omega 6

too much A acid can cause inflammation

-omega 6 can decrease coronary heart disease
Eicosanoid metabolism
-inflammation, coagulation, GI protection, pulmonary embolism

-A-acid
-PGi2, PGE2, ect.
-TXA2
-LTC2,LTE4,LTD4 (SRS-A)

-NSAIDS

-dietary modulation by omega 3