Systemic Response to Injury Flashcards by Carlos Altamirano

Protein signaling compounds that mediate cellular responses

Cytokines

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Cytokine: Induces muscle breakdown and cachexia through increased catabolism

TNF-α

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Cytokine: Induces fever through prostaglandin activity in anterior hypothalamus

IL-1

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Cytokine: Promotes β-endorphin release from pituitary

IL-1

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Cytokine: Promotes lymphocyte proliferation and Ig production

IL-2

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Cytokine: Elicited by all immunogenic cells as a mediator of acute phase response

IL-6

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Cytokine: Prolongs activated neutrophil survival

IL-6

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Cytokine: Chemoattractant for neutrophils, basophils, eosinophils, and lymphocytes

IL-8

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Cytokine: Activates macrophages via Th1 cells

IFN-γ

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Protect cells from deleterious effects of traumatic stress and, when released by damaged cells, alert the immune system of the damage

Heat shock proteins

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Bind both autologous and foreign proteins and thereby function as intracellular chaperones for ligands such as bacterial DNA and endotoxin

Heat shock proteins

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Cause cell injury through oxidation of unsaturated fatty acids within cell membranes

ROS

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Derived primarily by oxidation of membrane phospholipid arachidonic acid

Eicosanoids

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Enzyme involved in the oxidation of membrane phospholipid arachidonic acid

PLA2

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Action of phospholipase A2 is inhibited by

Corticosteroids

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Arachidonic acid undergoes the COX pathway to generate (2)

Cyclic endoperoxidases

1) PG
2) TXA2

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Arachidonic acid undergoes the LOX pathway to generate (2)

HPETE (5-Hydroperoxyeicosatetraenoic acid)

1) HETE (5-Hydroxyicosatetraenoic acid)
2) Leukotrienes

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MOA of Aspirin (NSAID prototype)

Nonselectively and irreversibly inhibits COX (COX-1 and 2)

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Aspirin anti-inflammatory effect is mediated by

Inhibition of COX-2 thereby inhibition of TXA2 production by platelets and decreases platelet aggregation

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GI toxicity of NSAIDs is mediated by

Inhibition of COX-1 hence PG synthesis (for HCO3 and mucous secretion)

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A viral illness for which aspirin is used is associated with what syndrome in children

Reye syndrome

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Reye syndrome is characterised by (2)

Acute non-inflammatory

1) Encephalopathy
2) Fatty degenerative liver failure

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Nonselective but reversible COX inhibitors (2)

1) Indomethacin

2) Ketorolac

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Selective COX-2 inhibitor with reduced risk of GI toxicity

Celecoxib

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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

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

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

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/F After injury, there is an increase in urinary nitrogen excretion

After an injury, loss of urinary nitrogen corresponds to a loss in lean body mass of ___% per day

1.5