What are three effects of reduced ATP during ischemia/hypoxia?
ATP-dependent sodium efflux pump cannot function, ATP dependent Calcium cation efflux transport cannot function, anaerobic glycolysis increases as an attempt to restore the ATP levels
What is the effect of decreased function of the ATP dependent sodium efflux pump?
increased intracellular sodium cations, decreased potassium ion concentration, influx of water, cellular swelling, decreased protein synthesis
What is the effect of decreased function of the ATP dependent calcium cation efflux?
activation of ATPases, phospholipases, proteases, endonucleases
What is the effect of increased Anaerobic glycolysis?
decreased glycogen stores, decreased pH level in the cell, decreased activity of cellular enzymes, detachment of ribosomes
How does ROS cause cellular injury?
functions as oxidizing agents
How does production of OFRs and ROS occur?
Incomplete reduction of O2 during respiration, Accepting or donating of electrons by transition metals, Absorption of X-rays, Detoxification or metabolism of chemicals in liver, Enzymes involved in inflammatory processes
What does ROS react with?
Fatty Acids, Proteins, DNA
What removes free radicals?
SOD, Glutathione peroxidases, catalase
What are the five contexts in which apoptosis occurs?
depravation of hormones or GF (menstruation), irreparable DNA damage, accumulation of misfolded proteins (alzheimer's), Immune system development, Embryogenesis (loss of vestigial tail)
increase in cell size but not number caused by increase work load, occurs by increased protein synthesis
increase in cell number but not size (breast growth)
decrease in cell size but not number caused by decreased work load, proteins degrade and protein synthesis decreases
one adult cell type is replaced by another
where does fat accumulation occur?
What causes fat accumulation?
ethanol consumption and diabetes
what is the effect of fat accumulation?
decreased liver function
what causes lipofuscin accumulation?
Damage due to ROS or OFR which indicates aging
what causes Hemosiderin accumulation?
break down of hemoglobin at sites of localized injury or hemmorrhage; associated with systemic overload of iron
death of cells of the vasculature, kidneys, lungs, and gastric mucosa
What are the three factors that contribute to cellular aging?
accumulation of damage (lipofuscin, incorrectly folded proteins/ cross-linked proteins, protein glycosylation, free radical damage), incomplete replication of protein ends by telomerase, reduced regenerative capacity of stem cells
What are the 5 local signs of acute inflammation?
Heat, redness, swelling, pain, loss of function
What does changes in vascular diameter lead to?
Vasodilation, increased viscosity, margination
What causes vascular permeability?
endothelial cell contraction which leads to gaps that leak fluids, direct injury to endothelial cells, leukocyte-dependent endothelial cell damage, increased fluid flow through endothelial cells, leakage from new blood vessels that form at the site of injury
What are the effects of vascular changes?
release of transudate, release of exudate, edema
What is margination?
WBC flow along the inner wall of blood cells due to changes in blood flow
What is rolling?
leukocytes tumble along the wall
What is transmigration?
leukocyte squeezes through the gaps in edothelial cells
What on endothelial cells binds to sialyl-lewis X-modified glycoprotein on leukocytes to slow down the leukocyte?
What on Leukocytes binds to ICAM-1 and UCAM on endothelial cells to cause firm binding?
What is chemotaxis?
leukocytes follow a chemoattractant gradient composed of bacterial peptides, complement components, and cytokines to the site of an infection
What receptor on leukocytes do chemoattractants bind?
7-transmembrane G-protein coupled receptor
What mediates phagocytosis allowing for regulation?
What is a phagosome?
phagocytic vacuole containing foreign bodies
What destroys the foreign body in the phagosome?
fusing with a lysosome which contains an oxidative burst
What are examples of circulating mediators of inflammation?
complement proteins, kinins, and coagulation factors
How are circulating mediators of inflammation activated?
What cells produce histamine?
mast cells, basophils, and platelets
When is histamine released?
physical injury, immune reactions, complement binding, neuropeptides, and cytokines
What effect does histamine have?
arteriolar dialation, increased vascular permeability, endothelial cell contraction; this results in swelling, edema, and congestion
What does COX metabolize AA into?
Lipoxygenases metabolize AA into?
leukotrienes and lipoxins
What do PGs cause?
vasodilation and edema; pain and fever
What type of drugs are COX inhibitors?
What do Leukotrienes cause?
vasoconstriction and increased vascular permeability; airway constriction
What do lipoxins do?
counteract the activity of leukotrienes
What cleaves Factor XII?
What two systems are triggered by Factor XII activation?
Kinin system, Complement system
triggers assembly of MAC
C3a and C5a
trigger histamine release
chemoattractant for WBC
obsonin which aids in phagocytosis
What are the three outcomes of acute inflammation?
restoration to pre-injury state, scaring or fibrosis, chronic inflammation
What are the three main characteristics of inflammation?
infiltration by macrophages, lymphocytes and plasma cells, continuous tissue destruction by inflammatory cells, extensive tissue repair including angiogenesis and fibrosis