Metabolic Regulation In Injury Flashcards
Does insulin phosphorylate or dephosphorylate things?
Dephosphorylate
Cascade that glucagon stimulates
.cAMP/PKA
. Causes release of glucose from liver via glycogen catabolism, gluconeogenesis, and FA release from adipose
. Epinephrine does same thing
What state is caused by injury
. Hypermetbolic styate
. basal metabolic rate (BMR) inc. proportional to injury
Cytokines
. Peptide signaling molecule assoc. w/ immune response
. Important ones: tumor necrosis tractor (TNF), IL-1, IL-6, interferon-gamma (IFN)
. Initiate and regulate metabolic response to injury.infection
Cortisol
. Steroid hormone synthesized in adrenal gland
. Slow time scale
. Generated normally in cycle w/ circadian clock
. Counter-regulatory hormone (opposes insulin, promotes catabolic processes)
Effects of cortisol
. Skeletal muscle: protein catabolism activated, synthesis inhibited
. Liver: gluconeogenesis stimulated
. Inhibited infmallatory response
. Inhibits fibroblast formation slowing wound healing
What happens I there is too much cortisol?
. From adrenal gland tumor (Cushing’s)
. Symptoms: truncates obesity, insulin resistance causing DM, poor immune system, poor wound healing
What happens w/ too little cortisol
. Most common Addison’s disease
. Symptoms: hypoglycemic from poor gluconeogenesis
. Dec. bp
. Stress causes drop in bp and patient goes into shock
In injury, balance btw insulin and counter-regulatory hormones shift in direction of ____
Counter regulatory hormones
. Causes insulin resistance
Basal metabolic rate
. Energy required by individual during physical, digestive, and emotional rest
What determines BMR
. Body surface area: greater surface area, more heat loss
. Age: kids need more energy than adults to grow
. Women have lower than men
. Regular exercise inc. BMR
How does starvation effect BMR
. Dec. up to 50%
What percentage increase in BMR for each degree C rise in body temp?
12% inc.
Effect of burns, severe infections, and prolonged lack of food on BMR
. Burns: inc. BMR 2 fold
. Severe infections: inc. BMR 50%
. Prolonged lack of food: dec. BMR
How does hypermetabolism help in injury
. Hyperglycemia for cells using aerobic metabolism in injured area (fibroblasts, macrophages, leukocytes)
. Kidney uses more glucose than usual
. AA released from skeletal muscle is muscle is uninjured to use for gluconeogenesis, Gln in intestines, substrates for protein synthesis by liver, plasma cells that make antibodies, and cells in wound healing
How does preoduction of proteins by liver change in response to injury?
. Makes less of albumin and transferrin
. Makes more C-reactive protein, serum amyloid A, haptoglobin (combines w/ harmful substances released during cell lysis), fibrinogen (promotes/regulates hemostasis), ceruloplasmin (delivers Cu to wound for collagen biosynthesis), component C3 (complement)
Complement cascade
. Initial step: antibody binds to infectious agent
. Final step causes lysis of foreign cell
. Series of step involving zymogens (key steps are proteolytic cleavage and conformational changes)
. Found in blood and lymph
C-reactive protein
. Protein Marker of inflammation
. Stimulates complement and promotes interaction btw pathogens and phagocytic cells
. Binds chromatin and histones to prevent autoimmune problems
. Enhances chemotaxis and phagocytosis
. Modulates platelet activation
. Inhibits IL-1 and TNF to regulate inflammation
Chromatin
Human DNA complexed w/ protein
Histones
Proteins found to DNA
Changes in lipid metabolism in response to injury
. Inc. counter-regulatory hormones cause stimulation in HSL via PKA phosphorylating it after activation by adenylate cylase and cAMP
. Helps catabolize TAGs w/ other lipases
. FAs exported and taken up by other tissues
Ketogenesis w/ injury
. Doesn’t happen
. There is insulin available
Muscle in injury
. Protein catabolism leads to muscle weakness
. Nitrogen excretion decreases if you provide good nutritional support (5% dextrose infusion)
. Percent muscle loss by administering propranolol
Propranolol
. Inhibits Epinephrine
. Counteracts hypermetbaolic state assoc. w/ injury
. Prevents excess catabolism and muscle loss
. Improves aerobic response to exercise in massively burned children