Kidney, liver, and endocrine complete Flashcards
Describe the anatomy of the nephron
The nephron is the functional unit in the kidney. Pay particular attention to the nephron as well as its blood supply
discuss the anatomy of the renal cortex and medulla
Renal cortex: Outer part of the kidney, it contains most parts of the nephron (glomerulus, bowman’s capsule, proximal tubules, and distal tubules)
Renal medulla: Inner part of the kidney
* it contains the parts of the nephron not in the renal cortex (loops of Henle and collecting ducts)
* the medulla is divided into pyramids
* the APEX of each pyramid is called the papilla. This region contains lots of collecting ducts
* the papilla drains urine into the minor calyces
*Multiple minor calyces converge to for the major calyces
* multiple major calyces converge to form the renal pelvis, which empties urine into the ureter
* the calyces, pelvis, and ureters have the capability to contract and push urine towards the bladder
how does the kidney contribute to the volume and composition of the extracellular fluid
there are 2 key hormones that govern the kidney regulates ECF volume and composition:
* Aldosterone- controls extracellular fluid volume (Na+ and water are reabsorbed together)
Antidiuretic hormone (vasopressin) controls plasma osmolarity (water is reabsorbed, but Na+ is not)
The kidneys also regulate potassium, chloride, phosphate, magnesium, hydrogen, bicarbonate, glucose, and urea
how do the kidneys help regulated blood pressure? what other systems also contribute to blood pressure regulation?
The kidneys provide intermediate and long term blood pressure control:
* long-term control of BP is carried out by the thirst mechanism (intake) and sodium and water excretion (output)
* intermedate-term control of BP is carried out by the renin-angiotensin-aldosterone system
*short-term control of BP is carried out by the baroreceptor reflex
How does the kidney eliminate toxins and metabolites?
glomerular filtration and tubular secretion clear the blood of metabolic byproducts, toxins, and drugs
like the liver, the kidney is capable of phase I and II biotransformation
how does the kidney contribute to acid-base balance? which other organ is essential to this process?
the key organs of acid-base balance include the lungs and the kidneys
* the lungs excrete volatile acids (CO2), and the kidneys excrete non-volatile acids
* the kidneys 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?
Erythropoietin is released in response to inadequate O2 delivery to the kidney. Clinical examples include: 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, what does it do?
calciferol is synthesized from ingested vitamin D or following exposure to ultraviolet light.
* in the liver, calciferol is converted to 25 [OH] vit D3 (inactive D3)
* in the kidneys (under control of parathyroid hormone), 25 [OH] vit D3 is converted to calcitriol (1,25 [OH]2 vitamin D3- the active form of vit D3)
Calcitriol has 3 functions. It stimulates:
* the intestine to absorb Ca+2 from food
* the bone to store Ca+2
* the kidney to reabsorb Ca+2 and phosphate
How much blood flow do the kidneys receive (% of CO and total flow)?
The kidneys receive 20-25% of the cardiac output (1000-1250 mL/min)
Discuss the path blood flows after it enter the renal artery
Filtration occurs at the glomerular capillary blood
Reabsorption and secretion occur at the peritubular capillary bed
Discuss the significance of renal autoregulation
The purpose of autoregulation is to ensure a constant amount of blood flow is delivered to the kidneys over a wide range of arterial blood pressures. Glomerular filtration becomes pressure-dependent when MAP is outside the range of autoregulation
* 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
There is little agreement about the range of RBF autoregulation. We like 50-180 mmHg
How does tubuloglomerular feedback affect renal autoregulation?
The juxtaglomerular apparatus is located in the distal renal tubule, specifically the region that passes between the afferent and efferent arterioles
Tubuloglomerular feedback about the sodium and chloride composition in the distal tubule affects arteriolar tone. In turn, this creates a negative feedback loop to maintain renal blood flow
when renal blood flow decreases, GFR also declines which reduces Na and CL delivery to the juxtaglomerular apparatus (sensed by the macula densa). This leads to the dilation of the afferent arterioles, which restores GFR. A lower Cl concentration in the ultrafiltrate triggers renin release from the juxtaglomerular cells, which activates the renin-angiotensin-aldosterone system. Angiotensin 2 causes constriction of the efferent arteriole, which also increases GFR.
Describe the myogenic mechanism of renal autoregulation
if the renal artery pressure is elevated, the myogenic mechanism constricts the afferent arteriole to protect the glomerulus from excessive pressure.
When the renal artery pressure is too low, the myogenic mechanism dilates the afferent arteriole to increase blood flow going to the nephron
how does the surgical stress response affect renal blood flow?
the surgical stress response 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
Vasoconstriction & sodium retention:
Ischemia, sepsis, surgical stress response
-> SNS- renin-angiotensin-aldosterone, antidiuretic hormone -> decrease in RBF, GFR, urine output, sodium excretion
Vasodilation and sodium excretion:
Prostaglandins and Atrial natriuretic peptide, kinins-> increase in RBF, GFR, Urine output, Sodium excretion
List the steps involved in the renin angiotensin aldosterone pathway
The RAAS plays an integral role in the regulation of systemic vascular resistance and the composition of the extracellular volume. By extension, it greatly influences cardiac output and arterial blood pressure
list 3 conditions that increase renin release, and give examples of each.
- Decreased renal perfusion pressure: Hemorrhage, PEEP, CHF, Liver failure with ascites, sepsis, diuresis
- SNS activation (Beta-1): circulating catecholamines, exogenous catecholamines
- Tubuloglomerular feedback: decreased sodium & chloride in distal tubule
where is the aldosterone produced, and what is its function?
Aldosterone is a steroid hormone that is produced in the zona glomerulosa of the adrenal gland.
By stimulating Na/K-ATPase in the principal cells of the distal tubules and collecting ducts, aldosterone causes:
* sodium reabsorption
* water reabsorption
* Potassium excretion
*hydrogen excretion
The net effect is that aldosterone increases blood volume but, it does NOT affect osmolarity. This is because the water follows in direct proportion when it’s reabsorbed into the peritubular capillaries.
Where is antidiuretic hormone produced, and what is its function?
ADH is 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
How ADH increases blood pressure:
* increased blood volume from V2 receptor stimulation in the collecting ducts (increase cAMP)
* Increased SVR from V1 receptor simulation in the vasculature ( Increase IP3, DAG, Ca+)
what clinical situations increase ADH release?
while anesthetic agents do not directly affect ADH homeostasis, they do impact arterial blood pressure and venous blood volume. In turn, these changes increase ADH release. Examples include:
*PEEP
*Positive-pressure ventilation
*hypotension
*hemorrhage
list 3 mechanisms that promote renal vasodilation.
There are three pathways that promote renal vasodilation
* Prostaglandins (inhibited by NSAIDs)
* atrial natriuretic peptide (increase RAP ->Na+ and water excretion)
* Dopamine-1 receptor stimulation (increased RBF)
compare and contrast the location and function of dopamine 1- and 2 receptors
There are two types DA1 and DA2.
* DA1 receptors are present in the kidney and the splanchnic circulation
*DA2 receptors are present on the presynaptic adrenergic nerve terminal
Location:
DA1 receptors: renal vasculature, Tubules
DA2 presynaptic SNS nerve terminal
2nd messenger:
DA1: increased cAMP,
DA2 receptor: Decreased cAMP
Function:
DA1- vasodilation, increased renal blood flow, increased GFR, Diuresis, Sodium excretion
DA2- decreased norepinephrine release
what is the mechanism of action of fenoldopam? why is it used?
Fenoldopam is a selective DA1 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
- it 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
Glomerular filtration rate = 125mL/min or around 20% of RBF
as you can see, the filtration fraction is 20%. This means that 20% of the renal blood flow is filtered by the glomerulus, and 80% is delivered to the peritubular capillaries
What are the 3 determinants of glomerular hydrostatic pressure?
Glomerular hydrostatic pressure is the most important determinant of GFR.
There are 3 determinants of glomerular hydrostatic pressure:
* arterial blood flow
* afferent arteriole resistance
* efferent arteriole resistance
How do changes in afferent arteriole diameter, efferent arteriole diameter, and plasma protein concentration affect net filtration pressure?
Describe the fate of sodium at each location in the nephron
Each percentage represents how much sodium is reabsorbed at each point in the nephron
Define reabsorption, secretion, and excretion.
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
what are the key functions of each part of the nephron
proximal tubule:
* bulk reabsorption of solutes
*bulk reabsorption of water
Loop of Henle (Descending):
* countercurrent mechanism (tubular fluid concentrate)
* High permeability to H2O
Loop of Henle (Ascending):
* countercurrent mechanism (tubular fluid diluted)
* No permeability to H2O
Distal Tubule:
* Fine tunes solute concentration (aldosterone and ADH)
Collecting duct:
*regulates final concentration of urine (aldosterone and ADH)
Describe the mechanism of action, clinical use, and key side effects of carbonic anhydrase inhibitors.
Carbonic anhydrase inhibitors:
* Acetazolamide
* Dorzolamide
MOA:
* Noncompetitive inhibition of carbonic anhydrase in the proximal tubule -> net loss of HCO3- and Na+ with a net gain of H+ and CL-
Clinical uses:
*open- angle glaucoma
* altitude sickness
* central sleep apnea syndrome
Key side effects:
* Metabolic acidosis
* Hypokalemia
Describe the mechanism of action, clinical use, and key side effects of osmotic diuretics
Osmotic diuretics:
* Mannitol
* Glycerin
* Isosorbide
MOA:
* Osmotic diuretics are sugars that undergo filtration but not reabsorption. They 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 HTN
Key side effects:
* Pulmonary overload in CHF patients
* Pulmonary edema
* If the blood-brain barrier is disrupted, mannitol will enter the brain and cause cerebral edema
describe the MOA, clinical use, and key side effects of loop diuretics.
Loop diuretics:
* furosemide
* Bumetanide
* Ethacrynic acid
MOA:
* Loop diuretics 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 sodium that remains in the tubule overwhelms the distal tubule’s reabsorption capability. Thus, a large volume of dilute urine is excreted. potassium, calcium, magnesium, and chloride are lost to the urine as well.
Clinical uses:
* HTN
* CHF/Pulmonary edema
* Hypercalcemia
Key side effects:
* Hypokalemia, hypochloremic metabolic alkalosis
* Hypocalcemia
* Hypomagnesemia
* Hypovolemia
* Ototoxicity (ethacrynic acid > furosemide)
* Reduced lithium toxicity
Describe the MOA, clinical use, and key side effects of thiazide diuretics
Thiazide diuretics:
* Hydrochlorothiazide
* Metolazone
*Indapamide
MOA:
*Thiazide inhibit the Na-Cl transporter in the distal tubule
Clinical uses:
*HTN
*CHF
*osteoporosis (reduces Ca excretion)
* Nephrogenic diabetes insipidus
Key side effects:
* Hyperglycemia- caution with DM
* Hypercalcemia
* Hyperuricemia - caution with gouty arthritis
* Hypokalemic, hypochloremic metabolic alkalosis
* hypovolemia
Describe the MOA, clinical use, and key side effects of potassium-sparing diuretics.
Potassium-sparing diuretics:
* Spironolactone
* Amiloride
* Triamterene
MOA:
* Amiloride and triamterene inhibit potassium secretion and sodium reabsorption in the collecting ducts. Their function is independent of aldosterone.
- Spironolactone exists in a subclass of potassium-sparing diuretics called aldosterone antagonists. By blocking aldosterone at mineralocorticoid receptors, spironolactone inhibits potassium secretion and sodium reabsorption in the collecting ducts
Clinical uses:
* To reduces potassium loss in a pt receiving a loop or thiazide diuretic
* Secondary hyperaldosteronism
Key side effects:
* Hyperkalemia (risk increased with concurrent use of NSAIDs, beta-blockers, and ACE inhibitors)
* Metabolic acidosis
* Gynecomastia
* Libido changes (spironolactone)
* Nephrolithiasis (triamterene)
List 3 tests of GFR and give the normal values for each
Glomerular function is measured by GFR. Clinical tests include:
- Blood urea nitrogen (10-20 mg/dL)
- Serum creatinine (0.7-1.5 mg/dL)
- Creatinine clearance (110-150 mL/min)
List 4 tests of tubular function and give the normal values for each.
Tubular function is measured by urine concentrating ability. Clinical tests include:
- Fractional excretion of Na+ (1-3%)
- Urine osmolality (65-1400 mOsm/kg). Note: if expressed as osmolarity, units of measurement are mOsm/L.
- 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?
Urea is the primary metabolite of protein metabolism in the liver (amino acids -> ammonia -> urea)
Because urea undergoes filtration AND reabsorption, it is a better indicator of uremic symptoms than as a measurement of GFR.
<8 mg/dL- overhydration, decreased urea production: Malnutrition, severe liver disease
20-40mg/dL
Dehydration
Increased protein input: high protein diet, GI bleed, hematoma breakdown
catabolism: trauma, sepsis
Decreased GFR
> 50mg/dL: decreased GFR
What is the BUN:Creatinine ratio? what do the numbers mean?
Since BUN undergoes filtration AND reabsorption and creatinine undergoes filtration but NOT reabsorption, the ratio of these substances in the blood can help us evaluate the state oh hydration.
* The normal ratio is 10:1
* A BUN:Cr ratio of >20:1 suggests prerenal azotemia
* The aforementioned non-renal causes of elevated BUN can also affect this ratio
What test is the best indicator of GFR? how is this value calculated?
Creatinine clearance is the most useful indicator of GFR
GFR = [(140-age) x body weight (kg)]/ [72 x serum Cr (mg/dL)] (x0.85 if female)
how do you interpret the fraction excretion (Fe) of sodium?
Fe(Na+) relates sodium clearance to creatinine clearance
- if Fe(Na+) < 1% then more sodium is conserved relative to the amount of creatinine cleared. This suggests prerenal azotemia
- If Fe(Na+) >3% then more sodium is excreted relative to the amount of creatinine cleared. This suggests impaired tubular function.
How can you use renal function tests to differentiate between prerenal oliguria and acute tubular necrosis?
what is the most common cause of perioperative acute kidney injury? Who is at the highest risk?
The most common cause of perioperative kidney injury is ischemia-reperfusion injury.
The following patients are at risk for acute kidney injury during the perioperative period:
* Pre-existing kidney disease
* Prolonged renal hypoperfusion
*Congestive heart failure
*Advanced age
*sepsis
*jaundice
*high-risk surgery (use of aortic cross-clamp and liver transplant)
what are the 3 modern methods used to classify the severity of acute renal injury?
Theses are 3 modern methods used to classify the severity of renal injury:
* RIFLE criteria: Risk, Injury, Failure, Loss, End-Stage Kidney Disease
Risk:
* SCr: increase in SCr to >1.5x baseline
* UOP< 0.5 mL/kg/hr for >6hrs
Injury:
* SCr: increase in SCr to >2x baseline
*UOP < 0.5 mL/kg/hr for >12 hrs
Failure:
*Increase in SCr to >2x baseline
*UOP <0.3 mL/kg/hr for >12hr or…Anuria for >12hr
Loss
* need for renal replacement therapy >4 weeks
End-stage
* need for renal replacement therapy >3 months
Acute Kidney Injury Network (AKIN)
Risk
* Increase in SCr > 1.5-2x baseline or…>0.3mg/dL
* UOP< 0.5 mL/kg/hr for >6hrs
Injury
* Increase in SCr >0.5mL/kg/hr for >12hrs
* UOP <0.5 mL/kg/hr for >12 hrs
Failure
* Increase in SCr >3x baseline or… >0.5mg/dL to absolute value >4mg/dL or….Need for renal replacement therapy
* UOP < 0.3mg/kg/hr >12 hr or… anuria for >12hr
last one is Kidney Disease Improving Global Outcomes (KDIGO)
These systems grade renal function on serum creatinine and urinary output. Serum creatinine (not urine output) is a more sensitive indicator of renal dysfunction. Their methods highlight that kidney injury occurs along a continuum.
what is the most common cause of prerenal injury? what is the treatment?
Prerenal injury: Hypoperfuison
* Perfusion impaired as a result of hypovolemia, decreased cardiac output, systemic vasodilation, renal vasoconstriction, or increased intra-abdominal pressure. There is no intrinsic damage…yet
Treatment:
* the risk of prerenal azotemia is reduced by maintaining MAP >65mmHg and providing appropriate hydration
* The restoration of renal blood flow with IVF, hemodynamic support, and/or PRBCs (if insufficient DO2)
* renal prostaglandins mediate vasodilation in the kidney. NSAIDs reduce prostaglandin synthesis, so avoid them if prerenal injury is a concern.
* An improvement in UOP following an intravenous fluid bolus confirms the diagnosis of prerenal azotemia
(Azotemia- elevated levels of urea and other nitrogen compounds in the blood)
What is intrinsic renal injury? What is the treatment?
Intrinsic injury: Parenchymal dysfunction
* While intrinsic injury can be caused by injury to the tubule, glomerulus, or the interstitial space, we will focus our discussion on acute tubular necrosis
* ATN is usually caused by ischemia (medulla at highest risk) or nephrotoxic drugs (IV contrast dye, abx, NSAIDs)
Treatment:
* Restore renal perfusion
* Supportive
What is postrenal injury? What is the treatment?
Postrenal injury: Obstruction
* Postrenal AKI is the result of an obstructive phenomena
* The source of the 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?
The most common cause of CKD is diabetes mellitus
The second most common cause of hypertension
Define the 5 stages of chronic kidney disease.
Chronic kidney disease is a progressive and irreversible disorder that reflects the ongoing inability of the kidneys to sustain their normal functions
We can use GFR to stage chronic kidney disease
Stage:
1: normal : GFR >90
2: Mildly decreased: GFR 60-89
3: Moderately decreased: GFR 30-59
4: Severely decreased: 15-29
5: Kidney Failure (requires dialysis): <15
How does uremia affect coagulation? how can bleeding be minimized in these patients?
Uremic pts are at increased risk of bleeding.
* bleeding time is a measure of platelet function. It is elevated by uremia and is the most accurate predictor of bleeding risk
* if PT, PTT, and platelet counts are normal
* The first-line treatment is desmopressin (von Willebrand factor VIII)
* Cryoprecipitate may be used to provide VIII-vWF, however, its use is associated with an increased risk of viral transmission
* Dialysis improves bleeding time, so it should be performed within 24hrs of surgery
why are patients with chronic kidney disease often anemic? what is the treatment for this?
Causes of anemia with CKD:
* 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 a first-line treatment because it increases the risk of HLA (human leukocyte antigens) sensitization and future rejection of a transplanted kidney.
How does chronic kidney disease affect acid-base balance?
Decreased excretion of non-volatile acid contributes to a gap metabolic acidosis
* Gap acidosis is the result of an accumulation of nonvolatile acids
* The pt will develop a compensatory respiratory alkalosis (HTN)
* Acidosis shifts the oxyhemoglobin association to the right. This partially compensates for anemia (release)
How does chronic kidney disease affect the serum potassium concentration? How is hyperkalemia treated in this patient population?
Hyperkalemia is the result of impaired excretion.
Dialysis is indicated when serum potassium exceeds 6 mEq/L
Other treatments that reduce serum potassium include:
* Glucose (25-50g) + Insulin (10-20 units)
* Hyperventilation ( for every 10 mmHg decrease in PaCO2, the serum potassium level is reduced by 0.5 mEq/L)
*calcium chloride (1g) does not change serum potassium concentration. Instead, it raises threshold potential in the myocardium and reduces the risk of lethal dysrhythmias
discuss the pathophysiology of renal osteodystrophy
renal osteodystrophy is caused by:
* decreased vit D production
*secondary hyperparathyroidism
Pathophysiology:
* An inadequate supply of Vit D impairs calcium absorption in the GI tract
* The body responds to hypocalcemia by increasing parathyroid hormone release. This action demineralizes bone to restore the serum calcium concentration
* The net result is a decreased bone density and increased risk of bone fractures
List 5 indications for dialysis
Dialysis is the concentration of AKI tx. There are 5 indications for its use:
* Volume overload
* Hyperkalemia
* Severe metabolic acidosis
* Symptomatic uremia
* Overdose with a drug that is cleared by dialysis
what are the most common complications of dialysis?
hypotension is the most common event during dialysis. This is due to intravascular volume depletion and osmotic shifts
what are the fresh gas flow recommendations for sevoflurane? why is this?
Compound A is produced when sevoflurane is degraded by soda lime. In theory, this can be toxic to the kidneys (there is no good human data)
The FDA recommends that sevo be administered at a rate of 1L/min for no more than 2 MAC hours. After 2 MAC hours have elapsed, the fresh gas flow should be increased to 2L/min
what factors increase compound A production with sevo?
Factors associated with increased compound A production include:
* High concentrations over a long period of time
* Low fresh gas flow
* High temperature of CO2 absorbent
* Increased CO2 production
* Desiccated soda lime
Discuss the use of succ’s in the pt with renal failure.
Opening of the nAChR at the neuromuscular junction can increase serum potassium by 0.5-1 mEq/L for up to 10-15 min
* Succ’s is safe in pts with renal failure with a normal potassium level
* in the pt with hyperkalemia (K+ >5.5mEq/L), the normal response to succ’s may increase serum potassium to a dangerous level
which class of neuromuscular blockers provides the most predictable duration of action in pts with chronic kidney disease?
Due to their organ independent elimination, cisatracurium and atracurium are more predictable agents in this population
discuss the use of the aminosteroid neuromuscular blocker in pts with chronic kidney disease.
Roc primarily undergoes hepatobiliary elimination. >70% hepatic and 10-25% renal. However, it is associated with an unpredictably increased duration of action. Possible causes include a reduced clearance. altered protein binding, and/or an increased potency.
Vecuronium is metabolized by 3-OH vecuronium. Its duration is prolonged as a function of decreased clearance and an increased elimination half-life. 40-50% metabolized by the liver and 50-60% by the kidney.
Pancuronium is primarily eliminated by the kidneys >85% and 15% liver. and has no use in this population
How do you dose the reversal agent for the pt with chronic kidney dx?
Both anitcholinesterases and anticholinergics used to reverse neuromuscular blockers undergo renal elimination, and thus share a similar increase in duration. They do not require dosage adjustments
Discuss the use of opioids in the pt with chronic kidney disease.
Morphine is metabolized to morphine-6-glucuonide. This product is more potent than morphine, and it relies on renal excretion. Accumulation can contribute to respiratory depression.
Meperidine is metabolized to normeperidine. Accumulation of normeperidine can cause convulsions.
Fentanyl, sufentanil, afentanil, and remifentanil do not produce active metabolites and are better choices with renal failure. Hydromorphone may or may not produce an active metabolite (depends on the reference)
Hydromorphone is metabolized to an active metabolite, hydromorphone-3-glucuronide. This can cause prolonged respiratory depression and myoclonus. The literature is inconsistent on this one. Whether or not hydromorphone produces an active metabolite, renal impairment does necessitate a dose reduction
what steps can be taken to prevent nephrotoxicity from radiographic constant media?
Prevention of contrast-induced nephropathy (CIN):
* 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
*IV hydration with 0.9% NaCl prior to administration of contrast dye
*Sodium bicarbonate injection or infusion
* N-acetylcysteine is a free radical scavenger. It has fallen out of favor for lack of efficacy.
how does rhabdomyolysis affect renal function?
Rhabdomyolysis and myoglobinemia are sequelae of direct muscle trauma, muscle ischemia, or prolonged immobilization
* Myoglobin binds oxygen inside of the myocyte
* when it is released into the circulation, it is freely filtered at the glomerulus. In the presence of acidic urine (pH <5.6), myoglobin precipitates in the proximal tubule
* This 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 patient with rhabdomyolysis?
Preventative strategies include:
* Maintenance of renal blood flow and tubular flow with IV hydration
* Osmotic diuresis with mannitol
* UOP should be kept >100-150 mL/hr
* Sodium bicarbonate and/or acetazolamide to alkalize the urine
As an aside, hemolysis from a hemolytic reaction is treated in the same way
which antibiotics are nephrotoxic?
Some antibiotics increase the risk of AKI. This risk is reduced with IV fluids, correction of correctable risk factors, and close monitoring of serum trough levels
Nephrotoxic antibiotics:
* Aminoglycosides (gentamycin, tobramycin, amikacin)
* Amphotericin B (antifungal)
* vancomycin- (glycopeptide antibiotic)
* Sulfonamide (Trimethoprim, sulfadiazine, Bactrim)
* tetracyclines (Lymecycline, methacycline, doxycycline)
* Cephalosporins (Cephalexin, ceftriaxone, cefotaxime)
What are calcineurin inhibitors, and how do they affect renal function?
Calcineurin inhibitors (cyclosporine and tacrolimus) are immunosuppressant agents used to prevent rejection of transplanted organs. Side effects include 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. This creates a dilutional effect that increases the risk of hyponatremia, hypo-osmolality, hemolysis, and hemoglobinuria (renal failure)
what is the risk of glycine when used for irrigation during TURP?
Glycine metabolism can increase ammonia production, and can reduce LOC and contribute to encephalopathy.
Glycine is an inhibitory neurotransmitter in the retina. It 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’re highly ionized, so they’re good conductors of electricity. Therefore, these fluids are contraindicated when unipolar electrocautery is used.
The introduction of bipolar cautery in newer resectoscope permits use of ionic solutions
Describe the presentation of TURP syndrome.
Cardiopulmonary:
* Circulatory overload:
* HTN
* Reflex bradycardia
* CHF
* Pulmonary edema
* Dysrhythmias
* Myocardial infarction
CNS:
* Restlessness
* N/V
* Cerebral edema
* Seizures
* Coma
Metabolic:
* Hyponatremia
Misc.:
* Hemolysis
* Hypo-osmolality
What is the treatment for TURP syndrome?
- Support oxygenation and cardiovascular support
- Tell the surgeon to abort the procedure
- Lab data: Electrolytes, hematocrit, creatinine, glucose, and 12- lead EKG
- If Na > 120mEq/L, then restrict fluids and give furosemide (loop diuretic)
- If Na <120mEq/L, then give 3% NaCl at <100 mL/hr (discontinue when Na+ >120 mEq/L)
- Correcting serum Na too quickly increases the risk of central pontine myelinolysis
- Midazolam may be used for seizures
- Proceed with tracheal intubation and mechanical ventilation if the pt has difficulty with oxygenation and/or pulmonary edema (chest auscultation and CXR will be helpful)
Discuss bladder perforation that can occur during TURP?
Bladder perforation can occur if the resectoscope punctures the bladder wall
* Inadvertent stimulation of the obturator nerve through the bladder wall can cause lower extremity movement, which may cause the resectoscope to puncture the bladder wall.
* This complication is more easily recognized in a conscious patient, especially if sensory anesthesia does not extend much beyond T10
* Presentation includes abdominal and/or shoulder pain
* A 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
* The pt will require emergent suprapubic cystostomy or possibly exploratory laparotomy
describe how extracorporeal shock wave lithotripsy breaks up kidney stones.
ESWL delivers shock waves in rapid succession that are directed at the stone.
* Because the 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, producing smaller small stone fragments that are eliminated via the urine
* It’s important that there’s nothing between the energy source and the stone.
list the absolute and relative contraindications to extracorporeal shock wave lithotripsy (ESWL).
absolute:
* 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?
The shock wave can produce dysrhythmias (probably due to mechanical influence), and 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.
The livers functional unit is the lobule (otherwise known as the acinus)
Arterioles: terminal branches of: hepatic artery and portal vein
Capillaries: sinusnoids
Venules: central vein
function of kupffer cells?
since portal vein blood drains the intestine, the liver receives a significant bacterial load.
Kupffer cells (part of the reticuloendothelial (fixed phagocytic cells) system) remove the bacteria before the blood drains into the vena cava
describe the flow of bile from its site of production to release into the duodenum.
The flow of bile:
* Bile is produced by the hepatocytes
* The canaliculi drain bile into the bile duct
* The bile ducts converge to form the common hepatic duct
* The cystic duct (from the gallbladder) and the pancreatic duct join the common hepatic duct before it empties into the duodenum
* The sphincter of Oddi controls the flow of bile released from the common hepatic duct
* Contraction of the sphincter of Oddi (narcotics) increase biliary pressure
How much blood flow does the liver receive (% of CO and total)?
The liver receives around 30% of CO (1500mL)
Which vessels supply blood to the liver? Which provides comparatively more blood flow? Which provides more oxygen?
The liver is supplied by 2 vessels: portal vein & hepatic artery
* Aorta -> Splanchnic organs -> portal vein -> liver
* Aorta -> Hepatic artery -> liver
Portal vein supplies (alpha 1):
* 75% of liver blood flow
* 50% of oxygen content (lower O2 saturation)
Hepatic artery supplies (alpha 1 and beta 2):
* 25% of liver blood flow
* 50% of oxygen content (higher O2 saturation)
Portal blood flow is determined by what circulation system?
The 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 HTN?
Portal vein:
Normal pressure- 7-10 mmHg
Diagnostic for portal HTN: >20-30mmHg
Sinusoids:
Normal: 0 mmHg
Diagnostic for portal HTN: >5mmHg
What is the hepatic arterial buffer response?
Hepatic artery perfusion pressure = MAP- Hepatic Vein pressure
Hepatic arterial buffer response: This is a fancy way of saying that a reduction in portal vein flow is compensated by an increased hepatic artery flow
- this response is mediated by adenosine (direct vasodilator effect only on hepatic artery, not portal vein)
- Severe liver dx impairs this response
How do general and neuraxial anesthesia affect hepatic blood flow?
General anesthesia as we all neuraxial anesthesia reduce liver blood flow as a function of decreased MAP
What coagulation factors are NOT produced by hepatocytes?
Since the hepatocytes produce so many proteins, its easier to learn what they do NOT produce:
- 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
What coagulation factors are dependent on vitamin K? What anticoagulants are dependent on Vitamin K?
Vitamin K is required to synthesize factors II, VII, IX, and X, and absorption of vitamin K is dependent on the presence of bile in the gut
(1972)
Anticoagulants that are dependent on Vitamin K: Proteins S,C,Z
what plasma proteins are produced by the liver?
The liver produces all of the plasma proteins except for immunoglobulins (gamma globulins).
- Albumin: Provides oncotic pressure and is a reservoir for acidic drugs
- Alpha-1 acid glycoprotein: is a reservoir for basic drugs
- Pseudocholinesterase metabolizes succinylcholine and ester-type local anesthetics
Discuss glycogenesis, glycogenolysis, and gluconeogenesis. What is the stimulus for each? How does each affect serum glucose?
Stimulus:
Hyperglycemia -> Release of insulin (pancreatic beta cells)- Metabolic process is glycogenesis-> glucose turned into glycogen (storage)
Stimulus:
Hypoglycemia-> Release of: Glucagon (pancreatic alpha cells) and Epi (adrenal medulla)-> metabolic process ( Glycogenolysis and gluconeogenesis) -> glucose is normalized by glycogen (storage)-> glucose and Non-carbohydrates turned to glucose such as amino acids, pyruvate, lactate, and glycerol (triglycerides)
the liver is an important regulator of serum glucose. It also clears insulin from the circulation. Therefore, pts with liver failure are at risk of hypoglycemia.
Discuss 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
- the deamination process produces a large quantity of ammonia. The 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?
Bilirubin:
* The 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 (this component is neurotoxic)
* Unconjugated bilirubin is lipophilic. It’s transported to the liver bound to albumin
* the liver conjugates bilirubin with glucuronic acid. This increases its 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:
* Normal value = 12-14 sec
* Very sensitive for acute injury ( Factor 5 and 7 t1/2 is 4-6hrs)
Albumin:
* Normal value= 3.5- 5.0 g/dL
* Not sensitive for acute injury (t1/2= 21 days)
Name 2 tests of hepatocellular injury
AST (10-40 units/L) and ALT (10-50 units/L)
* Marked elevation of both suggest hepatitis
* AST/ALT ratio > 2 suggest cirrhosis or alcoholic liver dx
Name 3 tests of biliary duct obstruction. Which is the most specific?
5’-nucleotidase (0-11 units/L) is the MOST specific indicator of biliary duct obstruction
Y Glutamyl transpeptidase (0-30 units/L)
Alkaline phosphatase (45-115 units/L) is not very specific (it’s also in bone, placenta, and tumors)
How can you use these hepatic function tests to aid your differential diagnosis of hepatic dysfunction?
Which type of viral hepatitis has the highest incidence?
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 content
Type C= Percutaneous
Type D= Percutaneous
What is the prescribed prophylaxis regimen after exposure to hepatitis 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 tx?
Glutathione is a substrate for many phase 2 conjugation reactions. It increases a substance’s water solubility so that the substance can be excreted in the bile or by the kidney
- Acetaminophen produces a toxic metabolite called N-acetyl-p-benzoquinoneimine ( NAPQI)
- With normal acetaminophen dosing, NAPQI is conjugated with glutathione. The conjugated metabolite is not toxic.
- Acetaminophen overdose consumes the liver’s supply of glutathione
- Since the conjugation substrate isn’t available, the concentration of NAPQI rises, and this leads to hepatocellular injury
Treatment consists of oral N-acetylcysteine within 8 hours of acetaminophen overdose
How can halogenated anesthetics cause hepatic injury? Which agent presents the greatest risk?
The liver metabolizes desflurane, isoflurane, and halothane to inorganic fluoride ions and trifluoroacetic acid (TFA)
Halothane hepatitis is believed to be the result of an immune-mediated reaction caused by TFA. Up to 20% of halothane is metabolized, so it makes sense that halothane metabolism produces significant quantity of TFA. By comparison 0.02% Des and and 0.2% Isoflurane are metabolized. These drugs produce minuscule quantities of TFA, however, there is a theoretical risk that they can cause hepatitis, particularly in sensitized patients.
Sevoflurane does not produce TFA.
What are the risk factors for halothane hepatitis?
Unless you provide anesthesia in a third world country, you’ll probably never touch halothane. You should still know this stuff, however.
Risk factors:
* Age >40
* Female gender
* Greater than 2 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
Second most common- Hepatitis C
Is the patient with acute hepatitis a candidate for surgery?
- If acute hepatitis: Non-emegergent surgery should be postponed until symptoms have resolved and liver function tests return to normal
- If chronic hepatitis- The pt may proceed to surgery so long as the condition is stable
Your primary objectives are to preserve hepatic blood flow and avoid drugs that can potentiate hepatocellular injury. Some pts may be sensitive to the CNS effects of anesthetic drugs, while alcoholics experience a higher tolerance
What anesthetic techniques can be used to maintain hepatic blood flow?
- Use isoflurane (preserve hepatic blood flow the best)
- Avoid halothane (Don’t use if in OR)
- Avoid PEEP (increases resistance to hepatic drainage)
- 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 pt 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 pt? why?
Anesthetic requirement:
* MAC is decreased in the acutely intoxicated pt
* MAC is increased in the chronic alcohol abuser that is not intoxicated
* Alcohol potentiates GABA. There is an increased effect of benzodiazepines
* Alcohol inhibits NMDA receptors
What are the signs, symptoms, and treatment for alcohol withdraw syndrome?
Alcohol abuse creates a state of dependency. Signs and symptoms of withdrawal begin 6-8 hrs after the blood alcohol concentration returns to normal and peak at 24-36 hrs
- Early s/sx: Tremors and disorder perception (hallucinations, nightmares)
- Late s/sx: Increased SNS activity (tachycardia HTN, Dysrhythmias), N/V, insomnia, confusion, agitation
- Treatment: Alcohol, beta-blockers, alpha-2 agonists
What are the signs, symptoms, and treatment for delirium tremens?
Delirium tremens occurs after 2-4 days without alcohol
* S/sx- grand mal seizures, tachycardia, hyper- or hypotension, and combativeness
* Treatment: Diazepam (or other benzo) and beta-blockers
Why are alcoholics susceptible to Wernicke-korsakoff syndrome
Alcoholics are often deficient in vit B12 (thiamine)
Wernicke-korsakoff syndrome is characterized by a loss of neurons in the cerebellum, and this is brought on by thiamine deficiency
List the etiologies of cirrhosis and the cause of each.
- Non-alcoholic fatty liver dx (most common cause of liver dx) - Fatty infiltration (d/t obesity, metabolic dx)
- Alcohol abuse: fatty infiltration
- Alpha-1- antitrypsin deficiency: Genetic (this diseases also causes emphysema)
- Biliary obstruction: Inflammation and tissue destruction
- Chronic hepatitis: Inflammation and tissue destruction
- Right-sided heart failure: Increased hepatic vascular resistance
- Hemochromatosis: Iron overload
- Wilson disease: Genetic (copper accumulates in the tissues)
What is cirrhosis?
Cirrhosis is characterized by cell death, where healthy hepatic tissue is replaced by nodules and fibrotic tissue. This reduces the number of functional hepatocytes as well as the number of sinusoids.
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.
- The number of blood vessels passing through the liver is reduced, which increases hepatic vascular resistance (Portal HTN)
- To partially offset the increased resistance, the body creates collateral vessels that bypass the liver; these are called portosystemic shunts
- Since this blood bypasses the liver, drugs and toxins (ammonia) remain in the systemic circulation for a longer period of time
What is the MELD score, and what do the numbers mean?
The MELD score uses a logarithmic calculation that examines 3 factors of hepatic function: Bilirubin, INR, and serum creatinine
- low risk= <10
- Intermediate risk= 10-15
- High risk = >15
Compare and contrast the architecture of the nervous system and endocrine system.
compare and contrast positive and negative feedback loops in the endocrine system
Compare and contrast how the hypothalamus communicates with the anterior and posterior pituitary glands.
the hypothalamus communicates with the posterior pituitary gland through a series of neural connections, and it communicates with the anterior pituitary gland with a group of releasing and inhibiting hormones
Name the 7 hypothalamic hormones, and identify their effects on the anterior pituitary gland.
Compare and contrast the presentation and treatment of SIADH and diabetes insipidus.
What are the 3 zones of the adrenal cortex? What substances does each synthesize?
The adrenal cortex has 3 zones that synthesize and release:
* Mineralocorticoids (aldosterone)
* glucocorticoids (cortisol)
* androgens (dehydroepiandrosterone)
Notice that the cortical layers (outside to inside) spell GFR.
Remember what each one releases with: “salt, sugar, sex”
Describe the steps involved in the renin-angiotensin-aldosterone system.
compare and contrast the glucocorticoid and mineralocorticoid potencies of the endogenous and synthetic steroids
pay attention to the following:
* no glucocorticoid effects = aldosterone
* No mineralocorticoid effects = dexamethasone, betamethasone, triamcinolone
How do you determine who should receive perioperative steroid supplementation?
The answer depends on how much exogenous steroid the pt is receiving and for how long.
What 4 endocrine hormones produced by the pancreas? Which cell types produce each one?
Describe the physiology of the insulin receptor.
the insulin receptor is made up of 2 alpha and 2 beta subunits that are joined together by disulfide bonds. When insulin binds to the receptor, the beta subunits activate tyrosine kinase, which then activates insulin-receptor substrates (IRS). The insulin cascade turns on the GLUT4 transporter, which increases glucose uptake by skeletal muscle and fat.
what is the difference between type I and type II diabetes mellitus?
Diabetes is classified as either type I or type II
* T1DM is characterized by a lack of insulin production
* T2DM is characterized by a relative lack of insulin and insulin resistance
Compare and contrast the onset, peak, and duration of the exogenous insulin preparations
