Unit 10: Kidney, Liver, & Endocrine Flashcards
Describe the anatomy of the renal cortex and medulla
Renal Cortex = Outer part of the kidney
-contains most parts of the nephron (glomerulus, Bowman’s capsule, proximal tubules, and distal tubules)
Renal Medulla = Inner part of the kidney
-contains parts of the nephron not in the renal cortex (loops of Henle and collecting ducts)
-divided into pyramids
-APEX of each pyramid is called the papilla (contains lots of collecting ducts)
-papilla drains urine into the minor calyxes
-multiple minor calyces converge to form the major calyxes which converge to form the renal pelvic which empties urine into the ureter
-calyces, pelvis, and ureters have the capability to contract to push urine towards the bladder
What is the nephron? Describe its anatomy
The functional unit in the kidney
What two hormones govern how the kidney regulates the volume and composition of the extracellular fluid?
Aldosterone: controls ECF volume – sodium and water are reabsorbed together
Antidiuretic Hormone (Vasopressin): controls plasma osmolarity – water is reabsorbed, but sodium is not
*Both act in the distal tubule and collecting duct
*kidneys also regulate potassium, chloride, phosphate, magnesium, hydrogen, bicarb, glucose, and urea
How do the kidneys help to regulate blood pressure? What other systems also contribute to BP regulation?
Long term BP control is carried out by the thirst mechanism (intake) and sodium/water excretion (output)
Intermediate BP control is carried out by the renin-angiotensin-aldosterone system
Short term BP control is carried out by the baroreceptor reflex
How does the kidney eliminate toxins and metabolites?
Glomerular filtration and tubular secretion
-like the liver the kidney is capable of phase I and II biotransformation
What two organs contribute to acid-base balance?
Lungs: excrete volatile acids (CO2)
Kidneys: excrete non-volatile acids – maintain acid-base balance by titrating hydrogen in the tubular fluid, which creates acidic or basic urine
What stimulates the kidney to release erythropoietin? What does EPO do after it is released?
Released in response to inadequate O2 delivery to the kidney
-examples includes: anemia, reduced intravascular volume, and hypoxia (high altitude, cardiac and/or pulmonary failure)
-EPO stimulates stem cells in the bone marrow to produce erythrocytes
-Severe kidney disease reduces EPO production and leads to chronic anemia
What is calcitriol and what does it do?
Calciferol –> synthesized from ingested vitamin D or following exposure to ultraviolet light
- converted to 25 [OH] vitamin D3 (inactive D3) in the liver
- 25 [OH] vitamin D3 is converted to calcitriol (1,25 [OH]2 Vitamin D3 - active form) in the kidney
Calcitriol stimulates:
- the intestine to absorb Ca2+ from food
- the bone to store Ca2+
- the kidney to reabsorb Ca2+ and phosphate
How much blood flow do the kidneys receive (% of CO and total flow)?
20-25% of the CO (1000 - 1250 mL/min)
Describe the blood flow through the kidney starting with the renal artery
- Renal Artery
- Renal Segmental Artery
- Interlobar Artery
- Arcuate Artery
- Interlobular Artery
- Afferent Arterioles
- Glomerular Capillary Bed –> filtration
- Efferent Arterioles
- Peritubular Capillary Bed –> reabsorption and secretion
- Venules
- Interlobular Vein
- Arcuate Vein
- Interlobar Vein
- Renal Segmental Vein
- Renal Vein
What is the significance of renal autoregulation?
Purpose is to ensure a constant amount of blood flow is delivered to the kidneys over a wide range of arterial blood pressures
GFR becomes pressure-dependent when MAP is outside the range of autoregulation (50-180)
- when renal perfusion is too low –> renal blood flow is increased by reducing renal vascular resistance
- when renal perfusion is too high –> renal blood flow is reduced by increasing renal vascular resistance
What is the myogenic mechanism of renal autoregulation?
If renal artery pressure is elevated the myogenic mechanism constricts the afferent arteriole to protect the glomerulus from excessive pressure
If renal artery pressure is too low the myogenic mechanism dilates the afferent arteriole to increase blood flow going to the nephron
How does tubuloglomerular feedback affect renal autoregulation?
Juxtaglomerular apparatus is located in the distal tubule (region that passes between the afferent and efferent arterioles)
Tubuloglomerular feedback about the sodium and chloride composition in the distal tubule affects arteriolar tone – creates a negative feedback loop to maintain renal blood flow
How does the surgical stress response affect renal blood flow?
It induces a transient state of vasoconstriction and sodium retention –> this persists for several days resulting in oliguria and edema
Vasoconstriction of the renal vasculature during this time predisposes the kidneys to ischemic injury and nephrotoxicity from drugs administered during the perioperative period
What are the steps involved in the renin angiotensin aldosterone pathway?
What three conditions increase renin release? Give examples of each
- Decreased Renal Perfusion Pressure: hemorrhage, PEEP, CHF, Liver failure w/ ascites, Sepsis, Diuresis
- SNS Activation (Beta-1): Circulating catecholamines, Exogenous catecholamines
- Tubuloglomerular Feedback: Decreased sodium and chloride in distal tubule
Where is aldosterone produced? What is its function?
Produced in the zona glomerulosa of the adrenal gland
By stimulating the Na/K-ATPase in the principal cells of the distal tubules and collecting ducts, aldosterone causes:
- sodium reabsorption
- water reabsorption
- potassium excretion
- hydrogen excretion
Net effect is aldosterone increases blood volume but it does NOT affect osmolarity (water follows the sodium in direct proportion)
Where is antidiuretic hormone produced? What is its function?
Produced in the supraoptic and paraventricular nuclei of the hypothalamus
It is released from the posterior pituitary gland in response to:
- increased osmolarity of the ECF
- decreased blood volume
ADH increased BP by:
- increased blood volume from V2 receptor stimulation in the collecting ducts (increased cAMP)
- increased SVR from V1 receptor stimulation in the vasculature (increased IP3, DAG, Ca2+)
What clinical situations increase ADH release?
-PEEP
-Positive-pressure ventilation
-Hypotension
-Hemorrhage
*anesthetic agents do not directly affect ADH homeostasis – impact arterial BP and venous blood volume thus increase ADH release
What three mechanisms promote renal vasodilation?
-Prostaglandins (inhibited by NSAIDs)
-Atrial Natriuretic Peptide (increased RAP –> Na+ and water excretion)
-Dopamine 1 receptor stimulation (increased RBF)
Where are dopamine-1 and dopamine-2 receptors located? What is each of their functions?
Dopamine-1:
-located in renal vasculature and tubules
-2nd messenger is increased cAMP
-function = vasodilation, increased RBF, increased GFR, diuresis, and sodium excretion
Dopamine-2:
-located in presynaptic SNS nerve terminal
-2nd messenger is decreased cAMP
-function = decreased norepinephrine release
What is the mechanism of action of fenoldapam? Why is it used?
Selective dopamine-1 receptor agonist that increases renal blood flow
-low dose fenoldopam (0.1-0.2 mcg/kg/min) is a renal vasodilator and increases RBF, GFR, and facilitates Na excretion without affecting arterial blood pressure
-may offer renal protection during aortic surgery and during cardiopulmonary bypass
How much of the renal blood flow is filtered at the glomerulus? Where does the rest go?
Renal Blood Flow = 1000 - 1250 mL/min
GFR = 125 mL/min or ~20% of RBF
*20% of RBF is filtered by the glomerulus and 80% is delivered to the peritubular capillaries
What are the three determinants for glomerular hydrostatic pressure?
- Arterial blood pressure
- Afferent arteriole resistance
- Efferent arteriole resistance
*glomerular hydrostatic pressure = most important determinant of GFR
How do changes in afferent arteriole diameter, efferent arteriole diameter, and plasma protein concentration affect net filtration pressure?
What are the definitions of reabsorption, secretion, and excretion related to the kidney?
Reabsorption: substance is transferred from the tubule to the peritubular capillaries
Secretion: substance is transferred from the peritubular capillaries to the tubule
Excretion: substance is removed from the body in the urine
What percent of sodium is reabsorbed at each point in the nephron?
- Proximal Tubule = 65%
- Loop of Henle (ascending thick) = 20%
- Distal Tubule = 5%
- Collecting duct = 5%
- Urine = 5%
What is the key function of the proximal tubule in the nephron?
Bulk reabsorption of solutes
Bult reabsorption of water
What is the key function of the descending Loop of Henle in the nephron?
Countercurrent mechanism (tubular fluid concentrated)
High permeability to H2O
What is the key function of the ascending Loop of Henle in the nephron?
Countercurrent mechanism (tubular fluid diluted)
No permeability to H2O
What is the key function of the distal tubule in the nephron?
Fine tunes solute concentration (Aldosterone and ADH)
What is the key function of the collecting duct in the nephron?
Regulates final concentration of urine (Aldosterone and ADH)
What is the mechanism of action, clinical use, and key side effects of Carbonic Anhydrase Inhibitors? Give examples
Noncompetitive inhibition of carbonic anhydrase in the proximal tubule –> net loss of bicarb and sodium with a net gain of hydrogen and chloride
Clinical Uses:
- open-angle glaucoma
- altitude sickness
- central sleep apnea syndrome
Key Side Effects:
- metabolic acidosis
- hypokalemia
Examples = Acetazolamide and Dorzolamide
What is the mechanism of action, clinical use, and key side effects of Osmotic Diuretics? Give examples
Sugars that undergo filtration but not reabsorption – inhibit water reabsorption in the proximal tubule (primary site) as well as the loop of Henle
- water is excreted in excess of electrolytes
Clinical Uses:
- free radical scavenging
- prevention of acute kidney injury (little evidence to support this)
- intracranial hypertension
Key Side Effects:
- volume overload in CHF patients
-pulmonary edema - if blood-brain barrier is disrupted, mannitol will enter the brain and cause cerebral edema
Examples = Mannitol, Glycerin, Isosorbide
What is the mechanism of action, clinical use, and key side effects of Loop Diuretics? Give examples
They poison the Na-K-2Cl transporter in the medullary region of the thick portion of the ascending loop of Henle (primary site) – the amount of Na that remains in the tubule overwhelms the distal tubule’s reabsorption capability –> large volume of dilute urine is excreted (K, Ca, Mg, and Cl are lost to urine as well)
Clinical Uses:
-HTN
-CHF / Acute pulmonary edema
-Hypercalcemia
Key Side Effects:
-hypokalemic, hypochloremic metabolic alkalosis
-hypocalcemia
-hypomagnesemia
-hypovolemia
-ototoxicity (ethacrynic acid > furosemide)
-reduced lithium clearance
Examples = Furosemide, Bumetanide, Ethacrynic acid
What is the mechanism of action, clinical use, and key side effects of Thiazide Diuretics? Give examples
Inhibit the Na-Cl transporter in the distal tubule
Clinical Uses:
-HTN
-CHF
-Osteoporosis (reduces Calcium excretion)
-Nephrogenic diabetes insipidus
Key Side Effects:
-hyperglycemia (caution with DM)
-hypercalcemia
-hyperuricemia (caution with gouty arthritis)
-hypokalemic, hypochloremic metabolic alkalosis
-hypovolemia
Examples = Hydrochlorothiazide, Metolazone, Indapamide
What is the mechanism of action, clinical use, and key side effects of Potassium-Sparing Diuretics? Give examples
Amiloride & Triamterene: inhibit potassium secretion and sodium reabsorption in the collecting ducts – function is independent of aldosterone
Spironolactone (subclass of K-sparing diuretics –> Aldosterone Antagonists): block aldosterone at mineralocorticoid receptors – inhibits potassium secretion and sodium reabsorption in the collecting ducts
Clinical Uses:
-reduce potassium loss in a patient receiving a loop or thiazide diuretic
-secondary hyperaldosteronism
Key Side Effects:
-hyperkalemia (increased risk w/ concurrent use of NSAIDs, beta-blockers, and ACE inhibitors)
-metabolic acidosis
-gynecomastia
-libido changes (spironolactone)
-nephrolithiasis (triamterene)
Examples = Spironolactone, Amiloride, Triamterene
What are the three clinical tests that measure GFR? What is the normal value for each?
Blood Urea Nitrogen (BUN) – 10-20 mg/dL
Serum Creatinine – 0.7-1.5 mg/dL
Creatinine Clearance – 110-150 mL/min
What four clinical tests measure tubular function? What is the normal value for each?
-Fractional Excretion of Na – 1-3%
-Urine Osmolality – 65-1400 mOsm/kg
-Urine Sodium Concentration – 130-260 mEq/day
-Urine Specific Gravity – 1.003-1.030
What is included in the differential diagnosis of a low BUN? How about a high BUN?
BUN < 8mg/dL:
- Overhydration
- Decreased urea production (malnutrition, severe liver disease)
BUN 20-40 mg/dL:
- Dehydration
- Increased protein input (high protein diet, GI bleed, Hematoma breakdown)
- Catabolism (trauma, sepsis)
- Decreased GFR
BUN >50 mg/dL:
- Decreased GFR
*urea = primary metabolite of protein metabolism in the liver – undergoes filtration and reabsorption thus better indicator of uremic symptoms than as a measurement of GFR
What is the BUN:Creatinine ratio? What do the numbers mean?
BUN undergoes filtration AND reabsorption
Creatinine undergoes filtration but NOT reabsorption
Ratio of these substances in the blood can help evaluate the state of hydration
Normal = 10:1
Ratio > 20:1 = suggests prerenal azotemia
*non-renal causes of elevated BUN can also affect the ratio
What test is the best indicator or GFR? How is this value calculated?
Creatinine Clearance = most useful indicator
GFR = [(140 - age) x Body Weight (kg)] / [72 x Serum Cr (mg/dL)]
How do you interpret the fraction excretion of sodium?
Fe(Na+) relates sodium clearance to creatinine clearance
-Fe(Na+) <1% = more sodium is conserved relative to the amount of creatinine cleared –> Suggests prerenal azotemia
-Fe(Na+) >3% = more sodium is excreted relative to the amount of creatinine cleared –> Suggests impaired tubular function
How can you use renal function tests to differentiate between prerenal oliguria and acute tubular necrosis?
Prerenal Oliguria:
- fractional excretion of Na+ <1%
- urinary Na+ <20 mEq/L
- urine osmolality >500 mOsm/kg
- BUN:Creatinine ratio >20:1
- sediment = normal or possible hyaline casts
Acute Tubular Necrosis:
- fractional excretion of Na+ >3%
- urinary Na+ >20 mEq/L
- urine osmolality <400 mOsm/kg
- BUN:Creatinine ratio 10-20:1
- sediment = tubular epithelial cells or granular casts
What is the most common cause of perioperative acute kidney injury? Who is at the highest risk?
Most common cause = ischemia-reperfusion injury
Highest Risk:
- pre-existing kidney disease
- prolonged renal hypoperfusion
- congestive heart failure
- advanced age
- sepsis
- jaundice
- high-risk surgery (aortic cross clamp and liver transplant
What are the three modern methods used to classify the severity of acute renal injury?
RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease)
AKIN (Acute Kidney Injury Network)
KDIGO (Kidney Disease Improving Global Outcomes)
*these systems grade renal function on serum creatinine and urinary output – serum creatinine (not urine output) is a more sensitive indicator of renal dysfunction
What is the RIFLE classification of acute renal injury?
Risk: increase in SCr to >1.5x baseline and UOP <0.5 mL/kg/hr for >6hr
Injury: increase in SCr to >2x baseline and UOP <0.5 mL/hr for >12hr
Failure: increase in SCr to >3x baseline or increase >0.5 mg/dL to absolute value of >4 mg/dL and UOP <0.03 mg/kg/hr for >12 hr or anuriea for >12 hr
Loss: need for renal replacement therapy >4 weeks
End-Stage: need for renal replacement therapy >3 months
What is the Acute Kidney Injury Network (AKIN) classification of acute renal injury?
Risk:
- increase in SCr >1.5x baseline or increase in SCr >0.3 mg/dL
- UOP <0.5 mL/kg/hr for >6 hrs
Injury:
- increase in SCr >2-3x baseline
- UOP <0.5 mL/hr for >12 hrs
Failure:
- increase in SCr >3x baseline or increase in SCr >0.5 mg/dL to absolute value >4 mg/dL or need for renal replacement therapy
- UOP <0.3 mL/kg/hr for >12 hrs or anuria for >12 hrs
What is the Kidney Disease Improving Global Outcomes (KDIGO) classification of acute renal injury?
Risk: increase in SCr >1.5-2x baseline within the past 7 days or increase in SCr >0.3 mg/dL within 48 hrs and UOP <0.5 mL/kg/hr for >6 hrs
Injury: increase in SCr >2-3x baseline and UOP <0.5 mL/hr for >12 hrs
Failure: increase in SCr >3x baseline or increase in SCr to absolute value of >4 mg/dL or need for renal replacement therapy and UOP <0.3 mL/hr for >12 hr or anuria for >12 hr
What is the most common cause of prerenal injury? What is the treatment?
Most Common Cause of Prerenal = Hypoperfusion
- perfusion is impaired as a result of hypovolemia, decreased CO, systemic vasodilation, renal vasoconstriction, or increased intra-abd pressure (no intrinsic damage yet)
Treatment:
- risk of prerenal azotemia is reduced by maintaining MAP >65 and providing appropriate hydration
- restoration of renal blood flow with IVF, hemodynamic support, and/or PRBCs
- renal prostaglandins mediate vasodilation in the kidney – NSAIDs reduce prostaglandin synthesis so avoid them in prerenal injury
- an improvement in UOP following an IVF bolus confirms diagnosis of prerenal azotemia
What is intrinsic renal injury? What is the treatment?
Intrinsic Injury = Parenchymal dysfunction
-can be caused by injury to the tubules, glomerulus or the interstitial space – focus on Acute Tubular Necrosis
Acute Tubular Necrosis - caused by ischemia (medulla at highest risk) or nephrotoxic drugs (IV contrast dye, abx, NSAIDs)
Treatment = restore renal perfusion and supportive care
What is postrenal injury? What is the treatment?
Postrenal Injury = Obstruction
-source of obstruction can arise anywhere between the collecting system and the urethra
Treatment = relieve the obstruction
What are the first and second most common causes of chronic kidney disease?
Most Common Cause = Diabetes Mellitus
Second Most Common Cause = Hypertension
What are the five stages of Chronic Kidney Disease?
Stage 1 (Normal) - GFR >90 mL/min
Stage 2 (Mildly Decreased) - GFR 60-89
Stage 3 (Moderately Decreased) - GFR 30-59
Stage 4 (Severely Decreased) - GFR 15-29
Stage 5 (Kidney Failure Dialysis) - GFR <15
How does uremia affect coagulation? How can bleeding be minimized in these patients?
Uremic patients are at INCREASED risk of bleeding
-bleeding time = measure of platelet function
-PT, PTT, and platelet counts are normal
-first line treatment is desmopressin (von Willebrand Factor VIII)
-Cryo may be used to provide VIII-vWF (use is associated with an increased risk of viral transmission)
-Dialysis improves bleeding time – should be performed within 24 hours of surgery
Why are patients with CKD often anemic? What is the treatment for this?
-Decreased erythropoietin production leads to normochromic normocytic anemia
-Excess parathyroid hormone replaces bone marrow with fibrotic tissue
Treatment:
-exogenous EPO or Darbepoetin + iron supplementation
-blood transfusion is not first-line treatment – increases risk of HLA sensitization and future rejection of a transplanted kidney
How does CKD affect acid-base balance?
Decreased excretion of non-volatile acid contributes to a gap metabolic acidosis
-gap acidosis = result of accumulation of nonvolatile acids
-pt will develop a compensatory respiratory alkalosis (hyperventilation)
-acidosis shifts oxyHgb dissociation curve to the right (right = release) – partially compensates for anemia
How does CKD affect the serum potassium concentration? How is hyperkalemia treated in this population?
Hyperkalemia = result of impaired potassium excretion
-dialysis is indicated when K+ >6 mEq/L
-glucose (25-50g) + insulin (10-20 units)
-hyperventilation (for every 10 mmHg decrease in PaCO2 – K+ decreases by 0.5 mEq/L)
-sodium bicarb (50-100 mEq)
-calcium chloride (1g) – doesn’t change K= level but raises threshold potential in myocardium reducing risk of lethal dysrhythmias
What is the cause and pathophysiology of renal osteodystrophy?
Caused by:
- decreased vitamin D production
- secondary hyperparathyroidism
Pathophysiology:
- inadequate supply of vitamin D impairs calcium absorption in the GI tract
- body responds to hypocalcemia by increasing parathyroid hormone release – action demineralizes bone to restore serum calcium concentration
- net result = decreased bone density and increased risk of bone fractures
What are the 5 indications for dialysis?
-Volume Overload
-Hyperkalemia
-Severe Metabolic Acidosis
-Symptomatic Uremia
-Overdose with a drug that is cleared by dialysis
What is the most common complication of dialysis?
Hypotension
-due to intravascular volume depletion and osmotic shifts
What are the fresh gas flow recommendations for sevoflurane? Why?
Admin at a rate if 1 L/min for no more than 2 MAC hours – after 2 MAC hours then increase to 2 L/min
-compound A is produced when sevo is degraded by soda lime – theory is this is toxic to the kidneys – NO HUMAN DATA
What factors increase compound A production with Sevo?
-High concentration over a long period of time
-Low fresh gas flow
-High temperature of CO2 absorbent
-Increased CO2 production
What is the consideration when using SUX in a patient with renal failure?
Opening of the nAChR at neuromuscular junction can increase serum K+ by 0.5-1 mEq/L for up to 10-15 min
-SUX = SAFE in patients with renal failure and a NORMAL potassium level
-pt w/ hyperkalemia (>5.5) normal response to SUX may increase K+ to dangerous level
Which class of neuromuscular blockers provides the most predictable duration of action in patients with CKD?
Cisatracurium and Atracurium
-due to their organ independent elimination
What are the considerations of using aminosteroid neuromuscular blockers in patients with CKD?
Rocuronium primarily undergoes hepatobiliary elimination – associated with unpredictably increased duration of action (possible causes include a reduced clearance, altered protein binding, and/or an increased potency)
Vecuronium is metabolized to 3-OH vecuronium – duration is prolonged as a function of decreased clearance and an increased elimination half-life
Pancuronium is primarily eliminated by the kidneys and has no use in the population
How do you dose the NMB reversal agent for the patent with CKD?
Do not require dosage adjustments
-both anticholinesterases and anticholinergics used to reverse NMB undergo renal elimination and share an increase in duration
What are the considerations for the use of opioids in the patient with CKD?
Morphine: metabolized to morphine-6-glucuronide – more potent than morphine and relies on renal excretion (accumulation can contribute to respiratory depression)
Meperidine: metabolized to normeperidine (accumulation can cause convulsions)
Fentanyl, Sufentanil, Alfentanil, and Remi: do not produce active metabolites and are better choices w/ renal failure
Hydromorphone: metabolized to an active metabolite, hydromorphone-3-glucuronide – can cause prolonged respiratory depression and myoclonus (inconsistent literature)
What steps can be taken to prevent nephrotoxicity from radiographic contrast meda?
-Use nonionic iso- or low-osmolar contrast instead of hyperosmolar contrast
-Use the lowest volume of contrast as the procedure will allow
-Withholding other drugs with known nephrotoxic effects
-Intravenous hydration with 0.9% NaCl prior to admin of contrast dye
-Sodium Bicarb injection or infusion
-N-acetylcysteine is a free radical scavenger (fallen out of favor for lack of efficacy
How does rhabdomyolysis affect renal function?
-Myoglobin binds oxygen inside the myocyte
-When it is released into the circulation, it is freely filtered at the glomerulus (in the presence of acidic urine - myoglobin precipitates in the proximal tubule)
-Results in tubular obstruction and acute tubular necrosis
-In addition - myoglobin scavenges nitric oxide, leading to renal vasoconstriction and ischemia
How can you prevent or minimize renal injury in the pt with rhabdomyolysis?
-Maintenance of renal blood flow and tubular flow with IV hydration
-Osmotic diuresis with mannitol
-UOP should be kept >100-150 mL/hr
-Sodium bicarb and/or acetazolamide to alkalize the urine
*hemolysis from hemolytic reaction is treated the same way
Which antibiotics are nephrotoxic?
-Aminoglycosides (gentamycin, tobramycin, amikacin)
-Amphotericin B
-Vancomycin
-Sulfonamide
-Tetracyclines
-Cephalosporins
*risk is reduced with IV fluids, correction of correctable risk factors, and close monitoring of serum trough levels
What are calcineurin inhibitors, and how do they affect renal function?
Calcineurin Inhibitors (Cyclosporine and Tacrolimus) – immunosuppressant agents used to prevent rejection of transplanted organs
Side Effects = HTN and renal vasoconstriction
Sirolimus is a non-calcineurin inhibitor that carries a much lower risk of nephrotoxicity
What is the risk of distilled water when used for irrigation during TURP?
Distilled water has an osmolality of zero – creates dilutional effect that increases risk of hyponatremia, hypoosmolality, hemolysis, and hemoglobinuria (renal failure)
What is the risk of glycine when used for irrigation during TURP?
Glycine metabolism can increase ammonia production – can reduce LOC and contribute to encephalopathy
It is also an inhibitory neurotransmitter in the retina – can cause blindness or blurry vision for up to 24-48 hours
Can 0.9% NaCl and/or LR be used as an irrigation solution for TURP? Why or why not?
Yes and No
-0.9% NaCl or LR would be great choices, however they are highly ionized, so they are good conductors of electricity – reason they are contraindication with unipolar electrocautery is used
*introduction of bipolar cautery in newer resectoscope permits use of ionic solutions
What is the cardiopulmonary presentation of TURP syndrome?
Circulatory Overload
-hypertension
-reflex bradycardia
-CHF
-pulmonary edema
-dysrhythmias
-MI
What is the CNS presentation of TURP syndrome?
-Restlessness
-Nausea and Vomiting
-Cerebral Edema
-Seizures
-Coma
What is the Metabolic presentation of TURP syndrome?
Hyponatremia
What is the miscellaneous presentation of TURP syndrome?
Hemolysis
Hypo-osmolality
What is the treatment for TURP syndrome?
-Support oxygenation and cardiovascular support
-Tell surgeon to abort procedure
-Lab data – electrolytes, hematocrit, creatinine, glucose, and 12-lead EKG
-If Na >120 –> restrict fluids and give + furosemide
-If Na <120 –> give 3% NaCl at <100 mL/hr (discontinue when Na >120)
-Correcting serum Na too quickly increases risk of central pontine myelinolysis
- Midazolam may be used for seizures
-Proceed with tracheal intubation and mechanical ventilation if pt has difficulty w/ oxygenation and/or pulm edema
How can bladder perforation occur during TURP?
Can occur if the resectoscope punctures the bladder wall – inadvertent stimulation of obturator nerve through bladder wall can cause lower extremity movement
-more easily recognized in a conscious patient (especially if sensory anesthesia doesn’t extend much beyond T10
-presentation includes abdominal and/or shoulder pain
-reduction of irrigation fluid return is an early sign of bladder rupture
-treatment is supportive (IVF, pressors, etc) with serial assessment of H&H and transfusion as indicated
-pt will require emergent suprapubic cystostomy or possibly exploratory laparotomy
How does extracorporeal shock wave lithotripsy break up kidney stones?
ESWL delivers shock waves in rapid succession that are directed at the stone
-because acoustic impedance of water and human tissue is roughly similar the shock wave moves through the body until it reaches the body-stone interface
-at this point the energy is released breaking up the stone – produces smaller stone fragments that are eliminated via the urine
-important that there’s nothing between the energy source and the stone
What are the absolute and relative contraindications to extracorporeal shock wave lithotripsy?
Absolute Contraindications:
- pregnancy
- risk of bleeding (bleeding disorder or anticoagulation)
Relative Contraindications:
- pacemaker/ICD
- calcified aneurysm of the aorta or renal artery
- UTI (untreated)
- obstruction beyond the renal stone
- morbid obesity
How does ESWL affect cardiac conduction? What is done to minimize this risk?
Shock wave can produce dysrhythmias – the pulse wave is timed to the R wave on the EKG to minimize the risk of “R-on-T” phenomenon
What is the functional unit of the liver? Describe its anatomy
Liver’s Functional Unit = The Lobule (also known as the acinus)
-arterioles –> terminal branches of hepatic artery and portal vein
-capillaries –> sinusoids
-venules –> central vein
What is the function of Kupffer cells?
Kupffer cells (part of the reticuloendothelial system) remove the bacteria before the blood drains into the vena cave
Describe the flow of bile from its site of production to release into the duodenum
-Bile is produced by the hepatocytes
-Canaliculi drain bile into the bile duct
-Bile ducts converge to form the common hepatic duct
-Cystic duct (from gallbladder) and pancreatic duct join the common hepatic duct before it empties into the duodenum
-Sphincter of Oddi controls flow of bile released from the common hepatic duct
-Contraction of sphincter of Oddi (narcotics) increases biliary pressure
How much blood flow does the liver receive (% of CO and total)?
~30% of Cardiac Output – 1500mL
Which vessels supply blood to the liver? Which provides comparatively more blood flow? Which provides more oxygen?
Portal Vein:
- aorta –> splanchnic organs –> portal vein –> liver
- 75% of liver blood flow
- 50% of oxygen content (lower O2 saturation)
Hepatic Artery:
- aorta –> hepatic artery –> liver
- 25% of liver blood flow
- 50% of oxygen content (higher O2 saturation)
What circulation system determines portal blood flow?
Portal vein receives venous blood that has passed through the splanchnic circulation
What is the normal portal vein pressure? What value is diagnostic of portal hypertension?
Normal = 7-10 mmHg
Portal HTN = >20-30 mmHg
What is the hepatic arterial buffer response?
Hepatic Artery Perfusion Pressure = MAP - Hepatic Vein Pressure
Hepatic arterial buffer response: a reduction in portal vein flow is compensated by an increased hepatic artery flow
-response is mediated by adenosine
-severe liver disease impairs this response
How do general and neuraxial anesthesia affect hepatic blood flow?
Reduce liver blood flow as a function of decreased MAP
What coagulation factors are NOT produced by hepatocytes? Where are each produced instead?
-Von Willebrand Factor –> vascular endothelial cells
-Factor III (Tissue Factor) –> vascular endothelial cells
-Factor IV (Calcium) –> diet
-Factor VIII (Antihemophilic Factor) –> liver sinusoidal cells (not hepatocytes) and endothelial cells
*since hepatocytes produce so many proteins, it’s easier to learn what they dont produce
What coagulation factors are dependent on vitamin K? what anticoagulants are dependent on vitamin K?
Vitamin K is required for synthesis of Factors II, VII, IX, and X
-absorption of vitamin K is dependent on the presence of bile in the gut
Anticoagulants that are dependent on vitamin K = Proteins S, C, Z
What plasma proteins are produced by the liver?
Liver produces all the plasma proteins expect for immunoglobulins (gamma globulins)
-Albumin: provides oncotic pressure and is reservoir for acidic drugs
-Alpha-1 Acid Glycoprotein: reservoir for basic drugs
-Pseudocholinesterase: metabolizes SUX and ester-type local anesthetics
What is the stimulus for glycogenesis? How does it affect serum glucose?
Stimulus = Hyperglycemia
-release of insulin from pancreatic beta cells
Glucose –> Glycogen (storage) –> lowers serum glucose
What is the stimulus for glycogenolysis? How does it affect serum glucose?
Stimulus = Hypoglycemia
-release of glucagon from pancreatic alpha cells
-release of epi from adrenal medulla
Glycogen (storage) –> Glucose –> increases serum glucose
What is the stimulus for gluconeogenesis? How does it affect serum glucose?
Stimulus = Hypoglycemia
-release of glucagon from pancreatic alpha cells
-release of epi from adrenal medulla
Non-Carbohydrates –> Glucose –> increases serum glucose
-amino acids
-pyruvate
-lactate
-glycerol (triglycerides)
What is the role of the liver and amino acid deamination? What happens when the liver is unable to perform this function?
Amino acid deamination allows the body to convert proteins to carbohydrates and fats – some of these are utilized in Kreb’s cycle to produce ATP
Produces a large quantity of ammonia – liver converts ammonia to urea, which is eliminated by the kidney
Failure to clear ammonia (hepatic failure or portosystemic shunting) leads to hepatic encephalopathy
Where does bilirubin come from? How is it cleared from the body?
-Erythrocyte’s life cycle is 120 days –> aged RBCs are processed by the reticuloendothelial cells in the spleen
-In the spleen: hemoglobin –> heme –> unconjugated bilirubin (neurotoxic)
-Unconjugated bilirubin is lipophilic –> transported to the liver bound to albumin
-Liver conjugates bilirubin with glucuronic acid (increases water solubility)
-Conjugated bilirubin is excreted into the bile, metabolized by intestinal bacteria and eliminated in the stool
What are the best tests of hepatic synthetic function? Which is best for acute injury? Why?
PT and Albumin
- PT = very sensitive for acute injury (factor 5 and 7 half life is 4-6 hours)
- Albumin = not sensitive for acute injury (half life is 21 days)
*normal PT = 12-14 sec
*normal Albumin = 3.5-5 g/dL
What are two tests of hepatocellular injury?
AST (Aspartate Aminotransferase)
ALT (Alanine Transaminase)
- marked elevation of both suggests hepatitis
- AST/ALT ratio >2 suggests cirrhosis or alcoholic liver disease
*normal AST = 10-40 units/L
*normal ALT = 10-50 units/L
What are three tests of biliary duct obstruction? Which is the most specific?
5’Nucleotidase (0-11 units/L) –> Most Specific Indicator
Y Glutamyl Transpeptidase (0-20 units/L)
Alkaline Phosphatase (45-115 units/L) –> not very specific, also in bone, placenta, and tumors
What causes prehepatic dysfunction? What hepatic function tests are affected?
Causes:
-Hemolysis
-Hematoma Reabsorption
Hepatic Function Test Changes:
-increased unconjugated bilirubin
What causes hepatocellular injury? What hepatic function tests are affected?
Causes:
- Cirrhosis
- Alcohol Abuse
- Drugs
- Viral Infection
- Sepsis
- Hypoxemia
Hepatic Function Test Changes:
- increased conjugated bilirubin
- increased AST/ALT
- increased PT
- no change in albumin (acute injury) or decreased albumin (chronic injury)
- no change or increased alkaline phosphatase
What causes cholestatic dysfunction? What hepatic function tests are affected?
Causes:
-Biliary Tract Obstruction
-Sepsis
Hepatic Function Test Changes:
-increased conjugated bilirubin
-increased AST/ALT in late disease
-increased PT in late disease
-decreased albumin in late disease
-increased alkaline phosphatase
-increased Y Glutamyl Transpeptidase 5’-nucleotidase
What is the percent incidence for each type of viral hepatitis?
Type A = 50%
Type B = 35%
Type C = 15%
Type D = Co-infection with type B
How is each type of viral hepatitis transmitted?
Type A = oral-fecal
Type B = percutaneous or sexual contact
Type C = percutaneous
Type D = percutaneous
What is the prescribed prophylaxis regimen after exposure to Hep A, B, or C?
Type A = pooled gamma globulin, Hep A vaccine
Type B = Hep B immunoglobulin, Hep B vaccine
Type C = interferon + ribavirin
How can acetaminophen cause hepatic injury? What is the treatment?
Glutathione is a substrate for many phase 2 conjugation reactions – increases a subs
How can acetaminophen cause hepatic injury? What is the treatment?
Glutathione is a substrate for many phase 2 conjugation reactions – increases a substance’s water solubility so that it can be excreted in the bile or by the kidney
Acetaminophen produces a toxic metabolite (N-acetyl-p-benzoquinoneimine) – normal dosing this is conjugated with glutathione
In acetaminophen overdose – consumes the liver’s supply of glutathione – concentration of NAPQI rises and leads to hepatocellular injury
Treatment = oral N-acetylcysteine within 8 hours of acetaminophen overdose
How can halogenated anesthetics cause hepatic injury? Which agent presents the greatest risk?
Liver metabolizes Des (0.02%), Iso (0.2%), and Halothane (20%) to inorganic fluoride ions and trifluoroacetic acid (TFA)
-Halothane hepatitis – result of immune mediated reaction caused by TFA
What are the risk factors for halothane hepatitis?
-Age >40
-Femal Gender
-Greater than two exposures
-Genetics
-Obesity
-CYP2E1 induction (alcohol, isoniazid, phenobarbital)
What are the first and second most common causes of chronic hepatitis?
Most Common = Alcoholism (alcohol is the most common cause of drug-induced hepatitis as well)
Second Most Common = Hep C
Is the patient with acute hepatitis a candidate for surgery? How about if they have chronic hepatitis?
Acute Hepatitis – non-emergent surgery should be postponed until symptoms have resolved and liver function tests return to normal
Chronic Hepatitis – pt may proceed to surgery so long as the condition is stable
*primary objectives are to preserve hepatic blood flow and avoid drugs that can potentiate hepatocellular injury
What anesthetic techniques can be used to maintain hepatic blood flow?
-Use Iso (preserves hepatic blood flow the best)
-Avoid Halothane
-Avoid PEEP
-Ensure normocapnia
-Liberal use of IV fluids
-Regional anesthesia is ok as long as there are no coagulation defects
Which drugs should be avoided in the patient with hepatitis?
Avoid hepatotoxic drugs or those that inhibit CYP450:
-Acetaminophen
-Halothane
-Amiodarone
-Antibiotics: PCN, Tetracycline, and Sulfonamides
How is the anesthetic requirement altered in the alcoholic patient? Why?
-MAC is decreased in the acutely intoxicated patient
-MAC is increased in chronic alcohol abuser that is not intoxicated
-Alcohol potentiates GABA (increased effect of benzodiazepines)
-Alcohol inhibits NMDA receptors
What are the signs, symptoms, and treatment for alcohol withdraw syndrome?
Early: tremors and disordered perception (hallucinations, nightmares)
Late: increased SNS activity (tachycardia, HTN, dysrhythmias), N/V, insomnia, confusion, agitation
Treatment: alcohol, beta-blockers, alpha-2 agonists
*symptoms begin 6-8 hours after the blood alcohol concentration returns to near normal and peak at 24-36 hours
What are the signs, symptoms, and treatment for delirium tremens?
Symptoms:
- grand mal seizures
- tachycardia
- hyper or hypotension
- combativeness
Treatment:
- diazepam (or other benzos)
- beta blockers
Why are alcoholics susceptible to Wernicke-Koraskof syndrome?
they are deficient in vitamin B (thiamine)
*Wernicke-Korsakoff syndrome is characterized by a loss of neurons in the cerebellum, and is brought on by thiamine deficiency
What are the etiologies of cirrhosis and the cause of each? (8)
Non-alcoholic Fatty Liver Disease (most common) – fatty infiltration d/t obestiy, metabolic disease
Alcohol Abuse – fatty infiltration
Alpha-1-Antitrypsin Deficiency – genetic (also causes emphysema)
Biliary Obstruction – inflammation and tissue destruction
Chronic Hepatitis – inflammation and tissue destruction
Right-Side Heart Failure – increased hepatic vascular resistance
Hemochromatosis – iron overload
Wilson Disease – genetic (copper accumulates in the tissues)
What is cirrhosis?
Characterized by cell death, where healthy hepatic tissue is replaced by nodules and fibrotic tissue
Reduces the number of functional hepatocytes as well as the number of sinusoids
*when blood can’t flow past the nodules this causes portal HTN – elevated portal pressure is transmitted to the splanchnic circulation
How does cirrhosis affect liver blood flow? What is the consequence of this?
As the number of hepatocytes dwindles, so does the liver’s ability to perform all of its essential functions:
- number of blood vessels passing through the liver is reduced –> increases hepatic vascular resistance (portal HTN)
- to partially offset the increased resistance, the body creates collateral vessels that bypass the liver (portosystemic shunts)
- since the blood bypasses the liver, drugs, and toxins (ammonia) remain in the systemic circulation for a longer period of time
What is the MELD score? What do the numbers mean?
Uses logarithmic calculation that examines 3 factors of hepatic function:
- Bilirubin
- INR
- Serum Creatinine
Low Risk = <10
Intermediate Risk = 10-15
High Risk = >15
What is the Child-Pugh score? What are the classes?
Examines 5 factors of hepatic function:
-Albumin
-PT
-Bilirubin
-Ascites
-Encephalopathy
Class A (5-6 points) = 10% risk of periop mortality
Class B (7-9 points) = 30 % risk
Class C (10-15 points) = 80% risk
*if a pt is class A or B and otherwise optimized - reasonable to proceed with surgery
*pt with class C should be managed medically until hepatic function improves
What cardiovascular changes accompany cirrhosis?
Hyperdynamic Circulation:
- decreased SVR and BP –> increased CO
- increased RAAS –> increased blood volume
- increased peripheral blood flow (shunting) –> increased SvO2
- decreased response to vasopressors
- diastolic dysfunction
Portal HTN:
- increased hepatic vascular resistance –> increased backpressure to proximal organs
- esophageal varices –> bleeding
- splenomegaly –> thrombocytopenia
Ascites:
- decreased oncotic pressure
- decreased protein binding
- increased volume of distribution
- drainage –> hypotension
What pulmonary changes accompany cirrhosis?
Restrictive Defect: ascites and/or pulmonary effusion reduce pulmonary compliance
Respiratory Alkalosis: hypoxemia –> compensatory hyperventilation
Hepatopulmonary Syndrome: pulmonary vasodilation –> intrapulmonary shunt –> hypoxemia
Portopulmonary HTN: PAP >25 mmHg in the setting of portal HTN
What is the etiology of hepatic encephalopathy? What is the treatment?
Decreased Hepatic Clearance –> Increased Ammonia –> Cerebral Edema –> Increased ICP
Treatment: lactulose, antibiotics, and reduced protein intake
What renal changes accompany cirrhosis?
Renal Hypoperfusion: decreased GFR –> increased RAAS –> Na+ and H2O retention (dilutional hyponatremia may occur)
Hepatorenal Syndrome: decreased GFR –> renal failure (liver transplant is the definitive treatment)
What is the TIPS procedure?
Transjugular Intrahepatic Portosystemic Shunt
-bypasses a portion of the hepatic circulation by shunting blood from the portal vein (hepatic inflow vessel) to the hepatic vein (hepatic outflow vessel)
-reduces portal pressure and minimizes back pressure on the splanchnic organs
-in turn it reduces the likelihood of bleeding from esophageal varices and reduces amount of ascites
*temporary treatment for hepatorenal syndrome
*hemorrhage is a significant risk
Which hormone stimulates bile release? What is the stimulus for release?
Cholecystokinin (CCK) stimulates gallbladder contraction – increases flow of bile into the duodenum
Production and Release = Duodenum
Release Due to –> food ingestion (fat and amino acids) and increased vagal stimulation (PNS = rest & digest)
What is the pathophysiology and treatment of Cholecystitis, Cholelithiasis, and Choledocholithiasis?
Cholecystitis: Inflammation of the gallbladder
- treatment = cholecystectomy
Cholelithiasis: Gallstones
- treatment = cholecystectomy
Choledocholithiasis = Stones in common bile duct (may be result of inflammation of pancreatic head which obstructs common bile duct)
- treatment = ERCP
Who is at highest risk for developing gallstone?
-Obesity
-Aging
-Rapid weight loss
-Pregnancy
-Women > Men
*The Three “F’s” – Fat, Female, 40
What are the signs and symptoms of gallstones?
-Leukocytosis
-Fever
-RUQ Pain (pain is worse with inspiration – Murphy’s Sign)
What drugs can be used to relax the sphincter of Oddi?
-Glucagon (increases risk of PONV)
-Naloxone (poor choice for surgical patient)
-Nitroglycerin
*Glycopyrrolate and Atropine may help as well
*Opioids can precipitate spasm of sphincter of Oddi – may cause false positive during cholangiogram
What drugs can be used to relax the sphincter of Oddi? (3)
-Glucagon (increases risk of PONV)
-Naloxone (poor choice for surgical patient)
-Nitroglycerin
*Glycopyrrolate and Atropine may help as well
*Opioids can precipitate spasm of sphincter of Oddi – may cause false positive during cholangiogram (real world - never have held narcotics for this reason)
Compare and contrast the architecture of the nervous system and endocrine system
Nervous System = Wired
- electrical –> chemical
- messengers: neurotransmitters
- released: synapse (close to the cell)
- target: specific cells (very precise)
- speed: fast
- duration: short
Endocrine System = Wireless
- travels in the blood
- messengers: hormones
- released: endocrine (cell releases substance that travels through bloodstream before it acts on different cells) – paracrine (cell releases a substance that acts on adjacent cells) – autocrine (cell releases substance that acts on the surface of the same cell)
- target: more widespread
- speed: slow
- duration: long
How does the hypothalamus communicate with the anterior pituitary gland?
Communicates with a group of releasing and inhibiting hormones
-releasing and inhibiting hormones are released from the hypothalamus into the hypophyseal portal vessels
-hormones are transported along the pituitary stalk by the hypophyseal portal vessels
-hypothalamic releasing and inhibiting hormones influence hormone secretion by the anterior pituitary gland
-releasing hormones increased pituitary output and inhibiting hormones reduce pituitary output
How does the hypothalamus communicate with the posterior pituitary gland?
Communicates through a series of neural connections
-in the hypothalamus: ADH is formed primarily in the supraoptic nuclei – oxytocin is formed primarily in the paraventricular nuclei
-ADH and oxytocin are carried by axonal transport along the pituitary stalk
-posterior pituitary gland releases ADH and oxytocin into the systemic circulation
What are the 7 hypothalamic hormones? What are their effects on the anterior pituitary gland?
- Luteinizing Hormone (releasing hormone) – increases follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Corticotropin (releasing hormone) – increases adrenocorticotropic hormone (ACTH)
- Thyrotropin (releasing hormone) – increases thyroid stimulating hormone (TSH)
- Prolactin (releasing hormone) – increases prolactin
- Prolactin (inhibiting hormone) – decreases prolactin
- Growth Hormone (releasing hormone) – increase growth hormone
- Growth Hormone (inhibiting hormone) – decreases growth hormone
Where is the pituitary gland located? What is another name for the anterior and posterior pituitary glands?
Resides in sella turcica – connected to hypothalamus via pituitary stalk
Anterior Pituitary = Adenohypophysis
Posterior Pituitary = Neurohypophysis
What hormones are released from the anterior pituitary gland? (6)
-Follicle-stimulating hormone
-Luteinizing hormone
-Adrenocorticotropic hormone
-Thyroid stimulating hormone
-Prolactin
-Growth hormone
*Remember “FLAT PiG”
What is the function of each of the anterior pituitary hormones?
- FSH
- LH
- ACTH
- TSH
- Prolactin
- Growth Hormone
-Follicle-stimulating hormone –> germ cell maturation and ovarian follicle growth (females)
-Luteinizing hormone –> testosterone production (males) and ovulation (females)
-Adrenocorticotropic hormone –> adrenal hormone release
-Thyroid stimulating hormone –> thyroid hormone release
-Prolactin –> lactation
-Growth hormone –> cell growth
What hormones are released from the posterior pituitary gland? What are their functions?
Antidiuretic Hormone –> water retention
Oxytocin –> uterine contraction and breast feeding
What are the causes, presentation, and treatment for SIADH?
SIADH = Too much ADH
-Traumatic brain injury (most common)
-Cancer (small cell carcinoma)
-Noncancerous lung disease
-Carbamazepine
Presentation = Hyponatremia
-euvolemic or hypervolemic
-hypotonic plasma osmolarity (<275 mOsm/L)
-low plasma sodium (<135 mEq/L)
-low urine output
-higher urine osmolarity than plasma osmolarity
-high urine sodium
Treatment:
-fluid restriction
-demeclocycline (decreases responsiveness to ADH)
-if pt is symptomatic or Na <120 give hypertonic NaCl (don’t correct > 1 mEq/L/hr)
What are the causes, presentation, and treatment for Diabetes Insipidus?
DI = Too Little ADH
- pituitary surgery (most common)
- traumatic brain injury
- subarachnoid hemorrhage
Presentation = Polyuria
- euvolemic or hypovolemic
- hypertonic plasma osmolarity (>290 mOsm/L)
- high plasma sodium (>145 mEq/L)
- high urine output
- lower urine osmolarity than plasma osmolarity
- normal urine sodium
Treatment:
- DDAVP or vasopressin
- supportive
What are the anesthetic implications of acromegaly?
-Distorted facial features (difficult mask)
-Large tongue, teeth, and epiglottis (difficult laryngoscopy)
-Subglottic narrowing and vocal cord enlargement (difficult ETT placement - use smaller tube)
-Turbinate enlargement (risk of epistaxis – avoid nasal intubation if possible)
-OSA is common
-Increased risk of HTN, CAD, and rhythm disturbances
-Glucose intolerance
-Skeletal muscle weakness
-Entrapment neuropathies are common
Compare and contrast T4 and T3
Thyroxine (T4):
-directly released from the thyroid
-concentration is the highest in the blood (think T4 as a delivery vehicle)
-more protein binding than T3
-less potent than T3
-7 day half-life
Triiodothyronine (T3):
-mostly extrathyroid conversion of T4 to T3
-a small amount is released from the thyroid
-concentration is highest in the target cell (T4 is converted to T3 – think of T3 as the active form)
-less protein binding than T4
-more potent than T4
-1 day half-life
How does iodine deficiency affect T3 and T4?
TSH stimulates the iodide pump – Iodine is a substrate that the thyroid requires to synthesize T3 and T4
When iodine is not available (dietary deficiency) – thyroid is unable to produce a sufficient quantity of T3 and T4
How does thyroid hormone affect cardiac function?
Increases myocardial performance independent of the ANS:
- increases chronotropy
- increases inotropy
- increases lusitropy
- decreases SVR
Effect on the ANS that impact cardiac function:
- increases number and sensitivity of cardiac beta receptors
- decreases number of cardiac muscarinic receptors
How does thyroid hormone affect the respiratory system?
Increases BMR –> Increases O2 Consumption –> Increases CO2 Production –> Increase Minute Ventilation (increased Vt and RR)
How does thyroid hormone affect MAC?
Hyper- and hypothyroidism DO NOT affect MAC
*they do affect speed of anesthetic induction when a volatile agent is used – Hyperthyroidism = slower induction (d/t higher CO) – Hypothyroidism = faster induction (d/t lower CO)
What is the most common etiology of hyperthyroidism? What are the other causes? (7)
-Grave’s Disease (most common)
-Myasthenia Gravis
-Multinodular Goiter
-Carcinoma
-Pregnancy
-Pituitary Adenoma
-Amiodarone (less common than hypothyroidism)
What is the most common etiology of hypothyroidism? What are the other causes? (6)
-Hashimoto’s Thyroiditis (most common)
-Iodine Deficiency
-Hypothalamic-Pituitary Dysfunction
-Neck Radiation
-Thyroidectomy
-Amiodarone (more common than hyperthyroidism)
How are TSH, T3, and T4 levels affected by hyperthyroidism and hypothyroidism?
Hyperthyroidism = Low TSH + High T3 and T4
Hypothyroidism = High TSH + Low T3 and T4
What is the difference between myxedema coma and cretinism?
Myxedema coma: occurs with end-stage hypothyroidism (coma is a consequent, not a cause, of severely impaired thyroid function)
Cretinism: caused by neonatal hypothyroidism that leads to physical and mental retardation
What 3 thionamides can be used to treat hyperthyroidism? What is their mechanism of action?
Thionamides = Propylthiouracil (PTU), Methimazole, and Carbimazole
MOA: inhibit thyroid synthesis by blocking iodine addition to the tyrosine residues on thyroglobulin
-PTU also inhibits the peripheral conversion of T4 to T3
*require 6-7 weeks to achieve a euthyroid state
*only available PO but can be crushed and given via OG
Why are beta blockers used to treat hyperthyroidism?
They reduce SNS stimulation and inhibit peripheral conversion of T4 to T3
What are contraindications to radioactive iodine?
Pregnancy
Breast feeding mothers
When is it okay for a patient with hyperthyroidism to undergo surgery? How about the hypothyroid patient?
Hyperthyroidism:
-do NOT proceed to elective surgery until pt is euthyroid (may require upwards of 6-8 weeks)
-emergency surgery warrants administration of a beta-blocker, potassium iodide, glucocorticoid, and PTU
Hypothyroidism:
-ok to proceed to surgery if mild to moderate disease
What is the best way to secure the airway in a patient with a large goiter?
Goiter can cause tracheal deviation and/or tracheomalacia
On boards –> Goiter = Awake Intubation
*next best response is a technique that maintains spontaneous ventilation
What anesthetic agents should be avoided in hyperthyroid patient? (4)
- Sympathomimetics
- Anticholinergics
- Ketamine
- Pancuronium
What is the presentation of thyroid storm? When does it typically present?
Thyroid Storm = Medical Emergency (can occur in hyperthyroid AND euthyroid pts)
Generally brought on by stressful events: infection, surgery, etc (most commonly occurs 6-18 hours after surgery)
Common S/Sx:
-fever >38.5*C
-tachycardia/ tachyarrhythmias (a-fib)
-HTN
-CHF
-shock
-confusion and agitation
-N/V
*Under anesthesia thyroid storm can mimic MH, pheochromocytoma, neuroleptic malignant syndrome, and light anesthesia
How do you manage the patient with thyroid storm?
Four B’s:
- Block synthesis (methimazole, carbimazole, PTU, potassium iodide)
- Block release (radioactive iodine, potassium iodide)
- Block T4 to T3 conversion (PTU, propranolol, glucocorticoids)
- Block beta receptors (propranolol, esmolol)
Other treatment:
- cardiopulmonary support
- active cooling measures (cold IVF, ice packs)
- PTU or methimazole can be given OGT if during surgery
- beta blockers
- treat fever with acetaminophen
- avoid aspirin (can dislodge T4 from plasma proteins –> increases unbound fraction)
- management is same in pregnant and non-pregnant patients
Why is hypocalcemia a potential complication of thyroidectomy? How and when does it present?
Resection of parathyroid glands (without reimplantation) –> hypocalcemia at least 6-12 hours after surgery
Most S/Sx of hypocalcemia are the result of increased nerve and muscle irritability:
-muscle spasm –> tetany
-laryngospasm
-mental status changes
-hypotension
-prolonged QT interval
-paresthesias
-Chvostek’s sign (tapping on the angle of the jaw -facial nerve/masseter muscle –> facial contraction on ipsilateral side)
-Trousseau’s sign (muscle spasm in hand or forearm in response to BP cuff inflation for 3 min)
How does hypothyroidism affect gastric emptying?
Associated with delayed gastric emptying –> Increases risk of aspiration
What are the 3 zones of the adrenal cortex? What substances does each synthesize?
Zona Glomerulosa: Mineralocorticoids (salt) –> Aldosterone
Zona Fasciculata: Glucocorticoids (sugar) –> Cortisol
Zona Reticularis: Androgens (sex) –> Dehydroepiandrosterone
*cortical layers (outside to inside) spell GFR and remember release with “salt, sugar, sex”
Explain the steps involved in the Renin-Angiotensin-Aldosterone System
How much cortisol is produced per day? What is the normal cortisol level?
Cortisol production = 15-30 mg/day
Normal Serum Level = 12 mcg/dL
*stress can increase cortisol production upwards of 100 mg/day with serum level up to 30-50 mcg/day during and after major surgery
How does cortisol affect cardiovascular function?
Cortisol improves myocardial performance by increasing the number and sensitivity of beta receptors on the myocardium
Cortisol is also required for the vasculature to respond to the vasoconstrictive effects of catecholamines
Compare and contrast the glucocorticoid and mineralocorticoid potencies of the endogenous and synthetic steroids
What are unique side effects of epidural triamcinolone?
Associated with higher incidence of skeletal muscle weakness
More likely to cause sedation (not euphoria) and anorexia (not increased appetite)
*Triamcinolone is commonly administered in epidural space to treat lumbar disc disease
What is Conn’s syndrome? How does it present?
Conn’s Syndrome = Too much aldosterone
-primary – increased aldosterone release from the adrenal gland
-secondary – usually due to increased renin release or aldosterone secreting tumor
S/Sx (aldosterone = mineralocorticoid – present as mineralocorticoid excess):
-HTN (sodium and water retention)
-Hypokalemia (potassium wasting)
-Metabolic alkalosis (H+ wasting)
Chronic consumption of what food can produce a syndrome that resembles hyperaldosteronism (Conn’s Syndrome)?
Long term licorice ingestion (glycyrrhizic acid)
What is the treatment for Conn’s Syndrome?
-Aldosterone Antagonists (spironolactone or eplerenone)
-Potassium supplementation
-Sodium restriction
-Removal of aldosterone secreting tumor
What is the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s Syndrome = Too much cortisol
Cushing’s Disease = Too much ACTH
What are the causes of Cushing’s syndrome?
Cushing’s Syndrome = Too much cortisol
Endogenous Causes = Over production of cortisol
-pituitary tumor (Cushing’s Disease)
-adrenal tumor
Exogenous Causes = Steroid Medications
What are glucocorticoid effects?
-Hyperglycemia
-Weight gain (central obesity, buffalo hump, moon face)
-Increased risk of infection
-Osteoporosis
-Muscle weakness
-Mood disorder
**Too much = Cushing’s Disease
**Too little = Addison’s Disease
What are mineralocorticoid effects?
-Hypertension (sodium and water retention)
-Hypokalemia (potassium wasting)
-Metabolic alkalosis (H+ wasting)
What are androgenic effects?
Women become masculinized (hirsutism, hair thinning, acne, amenorrhea)
Men become feminized (gynecomastia, impotence)
How does Cushing’s Syndrome present? Why?
Cortisol has glucocorticoid, mineralocorticoid, and androgenic effects so Cushing’s will present as an excess of these 3 things
What endocrine disorder can occur after transsphenoidal resection of pituitary gland?
Diabetes Insipidus (too little ADH)
*usually a transient complication
What are they types of adrenal insufficiency? How does it present?
Adrenal Insufficiency = Too little mineralocorticoid, glucocorticoid, and androgen
Primary (Addison’s): adrenal glands don’t secrete enough steroid hormone (most common is autoimmune)
Secondary: decreased CRH or ACTH release (most common is exogenous steroid use)
Presentation:
- muscle weakness/fatigue
- hypotension
- hypoglycemia
- hyponatremia
- hyperkalemia
- metabolic acidosis (usually mild)
- anorexia
- N/V
- hyperpigmentation of knees, elbows, knuckles, lips, and buccal mucossa
What is the treatment for adrenal insufficiency?
Steroid replacement therapy (15-30 mg cortisol equivalent/day)
What is acute adrenal crisis? How does it present?
Adrenal insufficiency is a chronic state, but can deteriorate into an Acute Adrenal Crisis if pt is faced with additional stress (infection, illness, sepsis, surgery) Medical Emergency
Presentation:
-hemodynamic instability collapse
-fever
-hypoglycemia
-impaired mental status
What is the treatment for acute adrenal crisis?
-Steroid replacement therapy (hydrocortisone 100 mg + 100-200 mg q24h)
-ECF volume expansion (D5NS is best)
-Hemodynamic support
Describe the surgical stress response in patients on chronic steroid therapy
Exogenous steroid supplementation suppresses ACTH release from the anterior pituitary gland – some pts on chronic steroid therapy won’t be able to increase cortisol release in response to perioperative stress
When should a patient receive perioperative steroid supplementation?
Should Receive “Stress Dose” Steroids When:
- prednisone dose = >20 mg/day for >3 weeks (there is risk of HPA suppression)
- prednisone dose = 5-20 mg/day for >3 weeks (there is possible risk of HPA suppression)
Does Not Need “Stress Dose” Steroids When:
- prednisone dose = <5 mg/day for any time period or any dose for <3 weeks (no risk of HPA suppression)
What are the 4 endocrine hormones produced by the pancreases? Which cell type produce each one?
Alpha Cells –> Glucagon
Beta Cells –> Insulin
Delta Cells –> Somatostatin
PP –> Pancreatic Polypeptide
What conditions stimulate insulin release?
Anything that raises blood glucose:
-PNS stimulation (occurs after eating a meal)
-SNS stimulation (increase blood glucose –> increased insulin release)
-Hormones (glucagon, catecholamines, cortisol, growth hormone)
-Beta agonists
*glucose = primary stimulator of insulin release from pancreatic beta cells
What conditions decrease insulin release?
Anything that reduces blood glucose:
-Hormones (insulin – decreased glucose –> decreased insulin release)
-Volatile anesthetics
-Beta antagonists
What is the physiology of the insulin receptor?
-Made up of 2 alpha and 2 beta subunits that are joined by disulfide bonds
-When insulin binds –> beta subunits activate tyrosine kinase –> activates insulin-receptor substrates (IRS)
-Insulin cascade turns on GLUT4 transporter –> increases glucose uptake by skeletal muscle and fat
What factors stimulate glucagon release?
Anything that reduces blood glucose:
-hypoglycemia
-stress
-trauma
-sepsis
-beta agonists
*glucagon is secreted by pancreatic alpha cells – catabolic hormone that promotes energy release from adipose and the liver
*physiologic antagonist to insulin
What factors inhibit glucagon release?
Anything that increases blood glucose:
-insulin
-somatostatin
What are other uses for glucagon?
Glucagon (1-5 mg IV) increases myocardial contractility, HR, and AV conduction by increasing intracellular concentration of cAMP (does this independently of the ANS)
Useful in the following situations:
-beta blocker overdose
-CHF
-low CO after MI or cardiopulmonary bypass
-improving MAP during anaphylaxis
Also administered during ERCP to relax biliary sphincter
What is somatostatin?
Somatostatin = Growth Hormone-Inhibiting Hormone
-regulates ENDOCRINE hormone output from the islet cells
Released by delta cells
-inhibits insulin AND glucagon
-inhibits splanchnic blood flow, gastric motility, and gall bladder contraction
What is pancreatic polypeptide?
Inhibits pancreatic EXOCRINE hormone secretion, gall bladder contraction, gastric acid secretion, and gastric motility
What are the diagnostic criteria for diabetes mellitus?
-Fasting Plasma Glucose >126 mg/dL
-Random Glucose Level >200 mg/dL + classic symptoms
-Two Hour Plasma Glucose >200 mg/dL during oral glucose tolerance test
-Hemoglobin A1c >6.5%
What is the classic triad of diabetes mellitus? Why does it occur?
Polyuria – Dehydration – Polydipsia
*hyperglycemia >180 mg/dL –> glycosuria –> osmotic diuresis –> hypovolemia –> classic symptom triad
What is the difference between type 1 and type 2 diabetes mellitus?
Type 1: characterized by lack of insulin production
Type 2: characterized by a relative lack of insulin + insulin resistance
What are the most common causes of T1DM and T2DM?
Type 1: autoimmune response (early in life)
Type 2: obesity (later in life, but prevalence is increasing in obese children)
What is diabetic ketoacidosis?
- Hyperglycemia (>250 mg/dL) but cells are starved for fuel
- Not enough insulin –> Ketoacidosis, Hyperosmolarity (from increased glucose), and dehydration
- Usually caused by infection
- More common with type 1 DM
- Metabolic acidosis causes kussmaul respirations
- Acetone causes fruity-smelling breath
Treatment = volume resuscitation, insulin, potassium after acidosis subsides
What is hyperglycemic hyperosmolar state?
-Hyperglycemia (>600 mg/dL) – significantly increases serum osmolarity (>330 mOsm/L)
-Enough insulin is produced to prevent ketosis but not hyperglycemia
-Usually caused by insulin resistance or inadequate production
-More common with type 2 DM
-Compared to DKA, HSS is associated with greater elevation in glucose and osmolarity
-Glycosuria leads to dehydration and hypovolemia
-Mild metabolic acidosis may occur (usually >7.3 and no anion gap)
Treatment = volume resuscitation, insulin, correct electrolytes
What are the long term complications associated with diabetes mellitus?
Microvascular: neuropathy (sensory, motor, autonomic), retinopathy, nephropathy
Macrovascular: coronary artery disease, peripheral vascular disease, cerebrovascular disease
Other: stiff joint syndrome, poor wound healing, cataracts, glaucoma
How does diabetes mellitus affect the autonomic nervous system?
-Painless myocardial ischemia (referred pain pathways are dysfunctional)
-Reduced vagal tone –> tachycardia
-Risk of dysrhythmias
-Orthostatic hypotension
-Impaired respiratory compensation to hypoxia and hypercarbia –> increased sensitivity to anesthetic drugs
-Delayed gastric emptying –> increased risk of aspiration
-Impaired thermoregulation –> increased risk of hypothermia
-Regional anesthesia may worsen neurologic defects in the patient with diabetic polyneuropathy
-Diarrhea and constipation
What is the prayer sign?
Diabetes mellitus can cause glycosylation of the joints –> stiff joint syndrome with reduced ROM of AO joint
Prayer sign suggests joint glycosylation and increased risk of difficult intubation
What is the mechanism of action of the biguanides? List an example
Inhibit gluconeogenesis and glycogenolysis in the liver and decrease peripheral insulin resistance
Example: Metformin
Key Facts:
-does not cause hypoglycemia
-risk of metabolic acidosis
-often used for polycystic ovarian disease
What is the mechanism of action of the sulfonylureas? List examples
Stimulates insulin secretion from pancreatic beta cells
Examples: Glyburide, Glipizide, Glimepiride
Key Facts:
-risk of hypoglycemia
-avoid if there is a sulfa allergy
What is the mechanism of action of the meglitinides? List examples
Stimulate insulin secretion from pancreatic beta cells
Examples: Repaglinide, Nateglinide
Key Facts:
-risk of hypoglycemia
What is the mechanism of action of the thiazolidinediones? List examples
Decrease peripheral insulin resistance and increase hepatic glucose utilization
Examples: Rosiglitazone, Pioglitazone
Key Facts:
-does not cause hypoglycemia
-black box warning d/t risk of CHF
What is the mechanism of action of the alpha-glucosidase inhibitors? List examples
Slows digestion and absorption of carbohydrates from the GI tract
Examples: Acarbose, Miglitol
Key Facts:
-does not cause hypoglycemia
What is the mechanism of action of the glucagon-like peptide-1 receptor agonists? List examples
Increases insulin release from beta cells, decreases glucagon release from alpha cells, and prolongs gastric emptying
Examples: Exenatide, Liraglutide
Key Facts:
-risk of hypoglycemia
What is the mechanism of action of the dipeptidyl-peptidase-4 inhibitors? List examples
Increase insulin release from pancreatic beta cells and decrease glucagon release from alpha cells
Examples: suffix -liptin
Key Facts:
-risk of hypoglycemia
What is the mechanism of action of the amylin agonists? List examples
Decrease glucagon release from pancreatic alpha cells and reduce gastric emptying
Examples: Pramlintide
Key Facts:
-risk of hypoglycemia if co-admin with insulin
-does not alter insulin levels
-may cause N/V
What are the very rapid-acting exogenous insulins? What is the onset, peak, and duration?
-Lispro
-Insulin Aspart
-Glulisine
Onset = 5-15 min
Peak = 45-75 min
Duration = 2-4 hours
What are the rapid-acting exogenous insulins? What is the onset, peak, and duration?
Regular Insulin
Onset = 30 min
Peak = 2-4 hours
Duration = 6-8 hours
What are the intermediate-acting exogenous insulins? What is the onset, peak, and duration?
NPH
Onset = 2 hours
Peak = 4-12 hours
Duration = 18-28 hours
What are the long-acting exogenous insulins? What is the onset, peak, and duration?
Detemir:
-onset = 2 hours
-peak = 3-9 hours
-duration = 6-24 hours
Glargine:
-onset = 1.5 hours
-peak = none
-duration = 20-24+ hours
What are the ultra long-acting exogenous insulins? What is the onset, peak, and duration?
Degludec
Onset = 2 hours
Peak = none
Duration = 40+ hours
What is the presentation, risks, and treatment of hypoglycemia in the perioperative period?
-Highest risk if insulin is given during fasting
-S/Sx: SNS stimulation (tachycardia, HTN, diaphoresis)
-Difficult to diagnose under GA (even harder if pt is on beta-blocker)
-Possible cause of delayed emergence
-Rebound hyperglycemia (Somogyi effect) may cloud diagnosis
-Treatment: D50 (50-100 mL) or glucagon (0.5-1 mg IV or SQ)
What is the association between insulin and allergic reactions?
Insulin allergy was more common when animal-derived insulin products were used
Chronic NPH use (or fish allergy) may sensitize pt to protamine
What drugs counter the hypoglycemia effect of insulin?
-Epinephrine
-Glucagon
-Cortisol
What drugs extend or enhance the hypoglycemic effect of insulin? (3)
- MAOIs
- Salicylates
- Tetracycline
What is the pathophysiology of carcinoid syndrome?
Carcinoid syndrome – associated with secretion of vasoactive substances from enterochromaffin cells
-usually associated with tumors of the GI tract, but can also arise from locations outside the GI tract as well (i.e. Lungs)
-these tumors tend to release histamine, serotonin, kinins, and kallikrein
What hormones are released by a carcinoid tumor? What are the systemic effects of each?
Histamine: bronchoconstriction, vasodilation, hypotension, flushing (head/neck)
Kinins and Kallikrein: bronchoconstriction, vasodilation, hypotension, flushing (head/neck), increased histamine release from mast cells
Serotonin: bronchoconstriction, vasodilation, hypertension, SVT, increased GI motility (diarrhea, abdominal pain)
**Most common signs = Flushing and Diarrhea
What are the signs and symptoms of carcinoid crisis?
Carcinoid Crisis = life threatening
-Tachycardia
-Hyper or hypotension
-Intense flushing
-Abdominal pain
-Diarrhea
What drugs are used in the treatment of carcinoid crisis?
Somatostatin (octreotide or lanreotide) – inhibit release of vasoactive substances from carcinoid tumors
Antihistamines – H1 & H2: diphenhydramine + ranitidine or cimetidine
5-HT3 Antagonists
Steroids
Phenylephrine or vasopressin for hypotension
What drugs should be avoided in the patient with carcinoid syndrome?
-Histamine releasing drugs: morphine, meperidine, atracurium, thiopental, and SUX
-SUX inducted fasciculations can cause hormone release from the tumor
-Exogenous catecholamines can potentiate hormone release
-Sympathomimetic agents: ephedrine and ketamine
Where in the nephron does each class of diuretic act?
- Carbonic Anhydrase Inhibitors = Proximal Convoluted Tubule
- Osmotic Diuretics = Proximal Tubule
- Loop Diuretics = Thick Ascending Loop of Henle
- Thiazide Diuretics = Distal Convoluted Tubule
- Potassium Sparing Diuretics = Late Distal Tubule to the Collecting Duct
