Systemic Response to Injury Flashcards
Protein signaling compounds that mediate cellular responses
Cytokines
Cytokine: Induces muscle breakdown and cachexia through increased catabolism
TNF-α
Cytokine: Induces fever through prostaglandin activity in anterior hypothalamus
IL-1
Cytokine: Promotes β-endorphin release from pituitary
IL-1
Cytokine: Promotes lymphocyte proliferation and Ig production
IL-2
Cytokine: Elicited by all immunogenic cells as a mediator of acute phase response
IL-6
Cytokine: Prolongs activated neutrophil survival
IL-6
Cytokine: Chemoattractant for neutrophils, basophils, eosinophils, and lymphocytes
IL-8
Cytokine: Activates macrophages via Th1 cells
IFN-γ
Protect cells from deleterious effects of traumatic stress and, when released by damaged cells, alert the immune system of the damage
Heat shock proteins
Bind both autologous and foreign proteins and thereby function as intracellular chaperones for ligands such as bacterial DNA and endotoxin
Heat shock proteins
Cause cell injury through oxidation of unsaturated fatty acids within cell membranes
ROS
Derived primarily by oxidation of membrane phospholipid arachidonic acid
Eicosanoids
Enzyme involved in the oxidation of membrane phospholipid arachidonic acid
PLA2
Action of phospholipase A2 is inhibited by
Corticosteroids
Arachidonic acid undergoes the COX pathway to generate (2)
Cyclic endoperoxidases
1) PG
2) TXA2
Arachidonic acid undergoes the LOX pathway to generate (2)
HPETE (5-Hydroperoxyeicosatetraenoic acid)
1) HETE (5-Hydroxyicosatetraenoic acid)
2) Leukotrienes
MOA of Aspirin (NSAID prototype)
Nonselectively and irreversibly inhibits COX (COX-1 and 2)
Aspirin anti-inflammatory effect is mediated by
Inhibition of COX-2 thereby inhibition of TXA2 production by platelets and decreases platelet aggregation
GI toxicity of NSAIDs is mediated by
Inhibition of COX-1 hence PG synthesis (for HCO3 and mucous secretion)
A viral illness for which aspirin is used is associated with what syndrome in children
Reye syndrome
Reye syndrome is characterised by (2)
Acute non-inflammatory
1) Encephalopathy
2) Fatty degenerative liver failure
Nonselective but reversible COX inhibitors (2)
1) Indomethacin
2) Ketorolac
Selective COX-2 inhibitor with reduced risk of GI toxicity
Celecoxib
Anti-inflammatory effect of omega 3 fatty acids (3)
1) Inhibits TNF release from hepatic Kupffer cells
2) Inhibits leukocyte adhesion
3) Inhibits leukocyte transmigration
Elevated during G- bacteremia, hypotension, hemorrhage, endotoxemia, and tissue injury
Kallikrein
Action of kinins (6)
1) Vasodilation
2) Increased capillary permeability
3) Tissue edema
4) Pain pathway activation
5) Inhibition of gluconeogenesis
6) Increased bronchoconstriction
Actions of serotonin
1) Vasoconstriction
2) Bronchoconstriction
3) Platelet aggregation
Associated with eosinophil and mast cell chemotaxis
Histamine (H4)
PSY nervous system transmits its efferent signals via
Acetylcholine
Vagus nerve potentially regulates early pro inflammatory mediator release, specifically
TNF
CNS regulates inflammation via
Vagus nerve
Stimulus for cortisol release
ACTH
In burn-injured patients, cortisol may be chronically elevated for how long
4 weeks
Cortisol impairs wound-healing by reducing what substances in the wound
1) TGF-β
2) IGF-I
Principal regulator of steroid synthesis
ACTH
Sequence in steroid synthesis (3)
1) Cholesterol converted to pregnenolone by ACTH
2) Pregnenolone converted to progesterone or 17α-OH-pregnenolone
3) Progesterone converted to 11-Deoxycorticosterone to corticosterone to aldosterone (mineralocorticoid)
3) Progesterone converted to 17α-OH-prrogesterone to 11-deoxycortisol to cortisol (glucocorticoid)
3) 17α-OH-pregnenolone converted to DHEA to androstenedione to testosterone to estradiol (sex steroid)
A steroid alcohol
Cholesterol
Cholesterol is a precursor of (5)
1) Cell membranes
2) Vitamin D (7-dehydrocholesterol)
3) Bile salts (cholic and chenodeoxycholic acid)
4) Adrenal hormones (aldosterone and cortisol)
5) Sex hormones (testosterone and estradiol)
Cholesterol is composed of (2)
1) 4 fused hydrocarbon rings (A-D)
2) 8-membered branched hydrocarbon chain (20-27) attached to the D-ring
3) Single hydroxyl group at C3 of the A ring to which a fatty acid can be attached to form cholesterol esters
Counter regulatory mediator that potentially reverses the anti-inflammatory effects of cortisol
Macrophage Migration-Inhibiting Factor
MMIF is stored and secreted by (2)
1) Anterior pituitary
2) Intracellular pools within macrophages
GH exerts downstream effects through (2)
1) Direct interaction with GH
2) Enhanced hepatic synthesis of IGF-I
Actions of GH and IGF-I (3)
1) Protein synthesis
2) Insulin resistance
3) Mobilization of fat stores
Catecholamines
1) Epinephrine
2) Norepinephrine
3) Dopamine
Elevations of plasma catecholamine levels last ___ after severe injury
24-48h
Overall action of insulin
Anabolic state
Hallmarks of critical illness due to the catabolic effects of circulating mediators (2)
1) Insulin resistance
2) Hyperglycemia
T/F Hyperglycemia is associated with immunosuppression and increased risk for infection
T
Normal healthy adult requires how many calories per day
22-25 kcal/kg/day
Initial hours after surgical or traumatic injury are metabolically associated with (2)
1) Reduced total body energy expenditure
2) Urinary nitrogen wasting
Short-term fasting, # of days
Less than 5 days
Principal sources of fuel in healthy adult
Protein and lipids
Most abundant source of energy in healthy adult
Lipids
Rapidly and preferentially depleted fuel stores
Hepatic glycogen
Short-term fasting: Fall of serum glucose concentration within
Less than 16 hours
Recycling of peripheral lactate and pyruvate for hepatic gluconeogenesis is accomplished by
Cori cylce
Precursors for hepatic gluconeogenesis
1) Peripheral lactate
2) Peripheral pyruvate
3) Alanine from skeletal muscle
Cori cycle is also known as
Lactic acid cycle
Metabolic pathway involving conversion of lactate (from the skeletal muscle) into glucose and brought back to the muscle for utilization
Cori cycle
Energy expense of Cori cycle
4 ATP molecules
T/F Lactate production is sufficient to maintain systemic glucose need during short-term fasting
F
Short-term fasting: Source of substrate for hepatic gluconeogenesis when lactate is insufficient
Amino acids
Amount of protein that must be degraded daily to provide amino acids for hepatic gluconeogenesis
75 g/d for a 70 kg adult
Proteolysis during starvation results from
1) Decreased insulin
2) Increased cortisol
Proteolysis during starvation results in increased excretion of
Urinary nitrogen in urine
Amount of urinary nitrogen excreted in urine during starvation
> =30 g/day
Normal amount of urinary nitrogen excreted per day
7-10 g
Effect on proteolysis by prolonged fasting
Reduced to 20 g/d
Effect on urinary nitrogen excretion by prolonged fasting
2-5 g/day
Why proteolysis and urinary nitrogen excretion are decreased during prolonged fasting
Adaptation by vital organs by using ketone bodies as their principal source of fuel
Ketone bodies become an important source of fuel for the brain after how many days of fasting
2
Ketone bodies gradually become the principal source of fuel for the brain after how many days of fasting
24 days
Injuries that poses the highest energy demands (2)
1) Major burns
2) Sepsis/peritonitis
Principal source of energy during critical illness and stressed states
Lipids
Lipolysis in injury occurs mainly in response to
Catecholamine stimulation of hormone-sensitive TAG lipase
Injury and severe infections induce a state of
Insulin resistance
T/F Increase in plasma glucose level in injury is proportional to the severity of injury
T
T/F After injury, there is an increase in urinary nitrogen excretion
T
After an injury, loss of urinary nitrogen corresponds to a loss in lean body mass of ___% per day
1.5
