Topic 4: Endocrine Flashcards
When we are on bypass (heart and lungs are being bypassed)- what does it mean for drug administration?
Heart and lungs not perfused
- not able to secrete normal hormones
- not part of drug metabolism
Deeper levels of anesthesia appear do what?
- To reduce or eliminate endocrine responses
- Also appear to reduce mortality
Posterior lobe aka
Neurohypophysis
Anterior Lobe aka
Adenohypophysis
Pituitary Gland has what two functions?
neural and endocrine
Posterior pituitary is what portion of the gland?
the “neurosecretory” portion—it’s essentially modified nervous tissue
Posterior pituitary secretes what?
ADH (vasopressin)
Oxytocin
Oxytocin does what?
released by what?
Positive feedback loop during labor
Milk letdown during lactation
The “Cuddle” hormone
released by post pituitary
High concentrations of ADH (Vasopressin) do what to – peripheral vascular resistance?
May increase peripheral vascular resistance
High concentrations of ADH (Vasopressin) do what to –cardiac contractility?
May decrease cardiac contractility
High concentrations of ADH (Vasopressin) do what to coronary blood flow?
May decrease coronary blood flow
High concentrations of ADH (Vasopressin) do what to renal vascular resistance?
Increases renal vascular resistance
High concentrations of ADH (Vasopressin) do what to renal blood flow?
Reduces renal blood flow
High concentrations of ADH (Vasopressin) do what to von Willebrand factor?
Stimulates release of von Willebrand factor
High concentrations of ADH (Vasopressin) do what to hemostasis?
May improve hemostasis
ADH (Vasopressin) is a potent regulator of what?
Regulates renal water excretion (POTENT)
What Stimulates Vasopressin Release?
Increase plasma osmolarity Decreased BV or decreased (or perceived) BP Hypoglycemia Angiotensin II Stress Pain
Venting keeps what low?
left atrial pressure low simulating low CBV (potent stimulant)
Can Vasopressin release be stopped while on bypass?
Magnitude of increase can be reduced but not eliminated
Pulsatile Flow effect on Vasopressin release?
No significant decrease during bypass – significant decrease immediately after – back to normal 48 hours post-op
-Strangely, no effect on U.O.
How to prevent large Vasopressin release with Drugs?
Anesthesia with large doses of synthetic opioids Fentanyl (50 μg/kg) or sufentanil Regional anesthesia (Works for non-cardiac procedures)
ADH concentrations increase markedly during CPB ___ of anesthesia or perfusion technique
irrespective
Anterior portion secretes what kind of hormones?
trophic hormones that regulate:
- Adrenal cortex** (ACTH)
- Thyroid** (TSH)
- Ovaries/Testes
- Growth (HGH)
Most damaging complication to pituitary
Pituitary Apoplexy
Pituitary Apoplexy is most common in what pts?
Rare, more common in patients with pituitary adenomas (benign tumor) usually diagnosed post hoc
Pituitary Apoplexy symptoms
Ptosis (droopy eyelids) opthalmoplegia (paralysis muscles controlling eye) nonreactive & dilated pupils decreased visual acuity hormonal defects
Pituitary Apoplexy treatment
Hormonal replacement (HGH) / hypophysectomy
Damage to pituitary usually blamed on what?
ischemia, hemorrhage, and edema of gland
produce norepinephrine?
Adrenal medulla
Peripheral sympathetic & central nerve terminal
Epinephrine concentration increases how much over CPB from preoperative levels?
10 fold
Norepinephrine concentration increases how much over CPB from preoperative levels?
4 fold
EPI PEAK on bypass
When target temperature reached
NOREPI PEAK in bypass
After release of cross-clamp and rewarming
Prevention of Catecholamine release?
As with vasopressin, magnitude of increase can be reduced but not eliminated…and the adrenal medulla is just one honking big sympathetic nerve
Reduce Catecholamine release with Propofol?
Propofol infusion during bypass (4 mg/kg/hr) versus single bolus injection diazepam (0.1 mg/kg)
-Significant reduction of [catecholamine]
Reduce Catecholamine release with anesthesia?
Deep anesthesia versus light
-Greater depth (regardless of type) gives significant reduction of [catecholamine] and decreased mortality (documented in peds)
Reduce Catecholamine release with opiod general anesthesia?
High dose opiod general anesthesia (fentanyl or sufentanil) plus thoracic epidural versus high dose opiod anesthesia alone
–Significant reduction of [catecholamine] during and after bypass
Reduce Catecholamine release with spinal block ?
General anesthesia with high spinal block (bupivacaine) versus general anesthesia alone
-Significant reduction of [catecholamine]
Reduce Catecholamine release with pulsatile vs non-pulsatile flow?
Pulsatile versus non-pulsatile flow
-Older studies – minimal difference due to “technique” and definition of “pulsatile”?
Cortisol
Corticosteroid (adrenal cortical hormone)
released in response to stress
increases blood sugar, increases stores of sugar in liver as glycogen
suppresses immune system
Cortisol increases what?
increases blood sugar
increases stores of sugar in liver as glycogen
Adrenocorticotropic hormone
Corticotropin /
promotes increased production & release of corticosteroids and cortisol
Acts as an appetite suppressant, anxietomimetic, and (conversely) a pro-inflammatory
Adrenocorticotropic hormone promotes what?
promotes increased production & release of corticosteroids and cortisol
Adrenocorticotropic hormone acts as what?
Acts as an appetite suppressant, anxietomimetic, and (conversely) a pro-inflammatory
Adrenal Cortical Hormones (Cortisol and Adrenocorticotropic) Increase may be attenuated by what?
Deeper levels of anesthesia
Addition of thoracic epidural
Carbohydrate metabolism regulated by: (5)
insulin glucagon cortisol growth hormone epinephrine
Glucose concentration increases?
Hyperglycemia—worse with hypothermia
Stay elevated for many hours post-CPB
hypoinsulinemia
Insulin levels decrease—worse with hypothermia
Insulin resistance: Type I DM
do not require increased insulin doses
Insulin resistance: Type II DM
do require increased insulin doses
Atrial Natriuretic Factor does what? antagonist of what?
Incredibly efficacious vasodilator
Almost the exact physiologic antagonist of aldosterone
Peptides released from cardiac atria
Atrial Natriuretic Factor released from what?
Peptides released from cardiac atria
Atrial Natriuretic Factor release triggered by? (5)
- atrial distention (such as a-fib)
- Β-adrenergic stimulation
- Angiotensin-II
- Hypernatremia
- Endothelins (the most potent vasoconstrictors known)
the most potent vasoconstrictors known
Endothelins
Atrial Natriuretic Factor does what? (5)
- increased glomerular filtration rate
- inhibits renin release
- reduced plasma concentrations of aldosterone
- antagonize renal vasoconstrictors
- reduce arterial blood pressure
Interestingly, ANF helps prevent ______ myocardium and has other ______ on cardiomyocytes and cardiac vascular endothelium
“scarring” of ischemic
anti-ischemic effects on
ANF concentrations reduced when on CPB?
Concentrations reduced during bypass
hypothermia
cross clamping
ANF concentrations rise when?
Concentrations rise during rewarming and post bypass
What happens to the relation between Atrial Naturetic factor concentration and atrial pressure during bypass and early post operative period?
normal relation lost during bypass and early post operative period
Renin-Angiotensin-Aldosterone regulates what?
atrial pressure, intravascular volume, electrolyte balance
what secretes renin ? why is renin secretion increased?
Juxtaglomerular apparatus secretes renin
-increased secretion due to sodium depletion, decreased blood volume, reduced renal perfusion
Aldosterone (increased concentration) stimulates what?
stimulates readsorption of sodium and secretion of potassium and hydrogen ion by renal distal tubules
Angiotensin II (increased concentration) increases what? (2)
- increased blood pressure by direct vasoconstriction
- stimulates release of aldosterone for adrenal glands
Research utilizing ACE-inhibitors and ARBS suggest that CPB temporarily breaks the linkage between what during and immediately post-bypass?
“breaks the linkage” between Renin-Angiotensin-Aldosterone and hypo- or hypertension
Eicosanoids metabolized by ?
lungs
Prostaglandins mostly related to ?
inflammation
Thromboxanes mostly related to?
injury
Endoperoxide prostaglandins H2 produces?
PGE2, PGF2alpha, PGD2
prostacyclin (PGI2) or thromboxane (TXA2)
PGE generally
vasodilator
PGF2alpha, PGD2
pulmonary vasoconstrictor
PGI2
disaggregates platelets, potent vasodilator
TXA2
platelet aggregator, potent vasoconstrictor
Prostacyclin & thromboxane increase when?
during bypass and begin to decrease shortly thereafter
Aprotinin is what? affect on prostacyclin?
protease inhibitor – reduces increase in thromboxane – no effect on prostacyclin – better preservation of platelet function
CPB can induce “sick euthyroid syndrome”, what levels are low?
T3 and T4 levels are low but the thyroid gland is apparently “normal”
CPB can induce “sick euthyroid syndrome” resulted from what?
The result of disruption of the thyrotropic feedback loop
“sick euthyroid syndrome” does giving thyroxine help?
Mixed evidence whether giving thyroxine helps (trophic and pro-metabolic effects) or hurts (possible increased risk of MIs)
things that stimulate histamine release? (5)
-opioids (morphine / meperidine)
-muscle relaxants (tubocurarine)
-antibiotics
-heparin
-protamine
Concentration increases with administration of heparin – remains elevated
Ionized Ca %
50%
bound to protein Ca%
40%
chelated Ca%
10%
Blood concentration of Ca maintained by?
parathormone and vitamin D (bones / kidney)
Give extra calcium only when the following three conditions are present (per your book):
1) ready to terminate bypass
2) ionized calcium is reduced
3) need to increase contractility and BP
Second most abundant intracellular cation
Mg
Mg key factor in enzyme systems (5)?
- transmembrane electrolyte gradients
- energy metabolism
- synthesis various messaging substances
- function of ion channels
- hormone secretion and action
Mg Ionized, bound and chelated
%’s?
Ionized (55%), bound protein (30%), chelated (15%)
is it possible have normal [plasma] but intracellular depletion of Mg?
YES
Mg does what during bypass?
Decreases during bypass
Decreased levels may associated with cardiac dysrhythmias
Mg does what?
Helps suppress arrhythmias
- direct myocardial membrane effect
- direct / indirect effect on cellular sodium and potassium
- antagonism of calcium entry into the cell
- prevention of coronary arterial spasms
- antagonism of catecholamine action
- improves myocardial oxygen supply / demand ration
- inhibition of calcium current during plateau phase of myocardial action potential
Mg is antagonist of what?
- antagonism of calcium entry into the cell (inhibition of calcium current during plateau phase of myocardial action potential)
- antagonism of catecholamine action
Supplemental magnesium typical dose?
Typically ~ 2 grams post-cross clamp removal
Changes in potassium concentration caused by?
- cardioplegia
- anesthetic drugs
- priming solutions
- renal function
- carbon dioxide tension
- arterial pH
- hypothermia (decrease as cool, increase as warm)
- insulin treatment of hyperglycemia moves glucose and potassium into cell)
Albumin may help reduce decrease in what concentration?
K