Unit 10: Kidney Liver & Endocrine2
Discuss bladder perforation that can occur during TURP?
- 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. - 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 patient will require emergent suprapubic cystostomy or possibly exploratory laparotomy.
What is the treatment for TURP syndrome.
- Support oxygenation and CV support - Tell surgeon to abort the procedure - Lab data: electrolytes, hematocrit, creatinine, glucose, and 12-lead EKG - If Na+ > 120 mEq/L, then restrict fluids and give + furosemide (loop diuretic) - If Na+ < 120 mEq/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 patient has difficulty with oxygenation and/or pulmonary edema (chest auscultation and CXR will be helpful)
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)
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 (increased cAMP). - increased SVR from V1 receptor stimulation in the vasculature ( increased IP3, DAG, Ca+)
What clinical situations increase ADH release?
-PEEP -Positive-pressure ventilation -Hypotension -Hemorrhage
Can 0.9% NaCl and/or LR be used as an irrigation solution for TURP? Why or why not?
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.
How does the kidney contribute to the volume and composition of the extracellular fluid?
2 key hormones that govern how 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) Kidneys also regulate potassium, chloride, phosphate, magnesium, hydrogen, bicarbonate, glucose, and urea.
LIst 3 mechanisms that promote renal vasodilation.
3 pathways that promote renal vasodilation: - Prostaglandins - Atrial natriuretic peptide (increase RAP -> Na+ and water excretion) - Dopamine-1 receptor stimulation (increase RBF)
Which antibiotics are nephrotoxic?
Antibiotics increase the risk of AKI. This risk is reduced with intravenous fluids, correction of correctable risk factors, and close monitoring of serum trough levels. Nephrotoxic antibodies: - Aminoglycosides (gentamycin, tobramycin, amikacin) - Amphotericin B - Vancomycin - Sulfonamide - Tetracyclines - Cephalosporins
Where is 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 the Na/K-ATPase in the principal cells of the distal tubules and collecting ducts, aldosterone causes: - Sodium reabsorption - Water reabsorption - Potassium excretion The net effect is that aldosterone increases blood volume but it does NOT affect osmolarity. This is because the water follows sodium in direct proportion when it's reabsorbed into the peritubular capillaries.
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 Krebs 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.
What is calcitriol, and 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] vitamin D3 [inactive D3] - In the kidney, (under control of parathyroid hormone), 25 [OH] vitamin D3 is converted to calcitriol (1,25 [OH]2 Vitamin D3 - the active form of vitamin D3) Calcitriol has 3 functions. It stimulates: - intestine to absorb Ca+2 from food - bone to store Ca+2 - Kidney. to reabsorb Ca+2 and phosphate.
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.
Describe the MOA, 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 presentation of TURP syndrome.
Cardiopulmonary: - Circulatory overload: - HTN - Reflex bradycardia - CHF - Pulmonary edema - Dysrhythmias - MI CNS: - Restlessness - Nausea and vomiting - Cerebral edema - Seizures - Coma Metabolic: - Hyponatremia MISC. - Hemolysis - Hypo=osmolality
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 b/c it increases risk of HLA sensitization and future rejection of a transplanted kidney.
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 sevoflurane be administered at a rate of 1 L/min for no more than 2 MAC hours. After 2 MAC hours have elapsed, the fresh gas flow should be increased to 2 L/min.
List the 3 conditions that increase renin release, and give examples of each.
Conditions that increase Renin Release - Causes 1. decreased renal perfusion pressure - hemorrhage, PEEP, CHF, liver failure with ascites, sepsis, diuresis 2. SNS Activation (Beta-1) - circulating catecholamines, exogenous catecholamines 3. Tubuloglomerular Feedback - the macula densa in the distal tubule contains chemoreceptors that monitor [Na+] and [Cl-] in the tubular fluid - decreased sodium & chloride in distal tubule.
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)]
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 patient will develop a compensatory respiratory alkalosis (hyperventilation) - Acidosis shifts the oxyhemoglobin dissociation curve to the right (right=release). This partially compensates for anemia.
How can you use renal function tests to differentiate between prerenal oliguria and acute tubular necrosis?
Dx Test - Prerenal Oliguria - Acute Tubular Necrosis FeNA+ (%) - < 1 - > 3 Urinary Na+ (mEq/L) - < 20 - > 20 Urine osmolality (mOsm/kg) - > 500 - < 400 BUN: Creatinine ratio - > 20:1 - 10-20:1 Sediment - Normal/poss hyaline casts - tubular epithelial cells/granular casts
Describe how extracorporeal shock wave lithotripsy breaks 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, 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.
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.
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 factors increase compound A production with sevoflurane?
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
How do you interpret the fraction excretion 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.
What is the mechanism of action of fenoldapam? Why is it used?
Fenoldopam is a selective DA1 receptor agonist that increases RBF. - Low dose fenoldopam (0.1-0.2 mcg/kgmin) 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.
Discuss the path blood follows after it enters the renal artery.
Filtration occurs at the glomerular capillary bed. Reabsorption and secretion occur at the peritubular capillary bed.
How do general and neuraxial anesthesia affect hepatic blood flow?
General anesthesia as well as neuraxial anesthesia reduce liver blood flow as a function of decreased MAP.
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.
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)
What are the 3 determinants of glomerular hydrostatic pressure?
Glomerular hydrostatic pressure is the most important determinant of GFR. 3 determinants of glomerular hydrostatic pressure - arterial blood pressure - afferent arteriole resistance - efferent arteriole resistance
how can acetaminophen cause hepatic injury? what is the treatment?
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.
What is the risk of glycine when used for irrigation during TURP?
Glycine metabolism can increase ammonia production, and this 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.
What is the hepatic arterial buffer response?
Hepatic Artery Perfusion Pressure = MAP - Hepatic Vein Pressure Hepatic arterial buff 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 - Severe liver disease impairs this response.
Which vessels supply blood to the liver? Which provides comparatively more blood flow? Which provides more oxygen?
Liver is supplied by 2 vessels: portal vein & hepatic artery - Aorta -> Splanchnic organs -> Portal vein - > Liver - Aorta -> Hepatic artery -> Liver Portal vein supplies: - 75% of liver blood flow - 50% of oxygen content (lower O2 saturation) Hepatic artery supplies: - 25% of liver blood flow - 50% of oxygen content (higher O2 saturation)
How much blood flow does the liver receive (% of CO and total)?
Liver receives ~30% of the CO (1500mL)
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. Large volume of dilute urine is excreted. Potassium, calcium, magnesium, and chloride are lost to the urine as well. Clinical uses: - HTN - CHF/acute pulmonary edema - Hypercalcemia Key side effects: - Hypokalemic, hypochloremic metabolic acidosis - Hypocalcemia - Hypomagnesemia - Hypovolemia -Ototoxicity (ethacrynic acid > furosemide) - reduced lithium clearance
Discuss the use of succinylcholine in the patient with renal failure.
Opening of the nAChR at the neuromuscular junction can increase serum potassium by 0.5 - 1.0 mEq/L for up to 10-15 min. - Succinylcholine is safe in patients with renal failure and a normal potassium level. - In the patient with hyperkalemia (K+ > 5.5 mEq/L), the normal response to succinylcholine may increase serum potassium to a dangerous level.
Describe the MOA, 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 AKI - intracranial HTN Key Side effects: - Volume overload in CHF patients - pulmonary edema - If BBB is disrupted, mannitol will enter the brain and cause cerebral edema.
What are the best tests of hepatic synthetic function? Which is best for acute injury? Why?
PT: - Normal value = 10.9 -12.5s - Very sensitive for acute injury (factor V and VII t/2 is 3-6 hrs) Albumin: - Normal value = 3.5 - 5.0 g/dL - Not sensitive for acute injury (t1/2 = 21 days)
What is the normal portal vein pressure? What value is diagnostic of portal HTN?
Portal Perfusion Pressure = Portal Vein Pressure - Hepatic Vein Pressure Portal vein Normal pressure: 7-10 mmHg Diagnostic for portal HTN: > 20-30 mmHg Sinusoidal Normal pressure: 0 mmHg Diagnostic for portal HTN: > 5mmHg
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
Describe the MOA, clinical use, and key side effects of potassium-sparing diuretics.
Potassium-sparing diuretics: - Spironolactone - Amiloride - Triamterene MOA: - Amiloride and triamterenene inhibit potassium secretion and sodium reabsorption in the collecing ducts. Their function is independent of aldosterone. - Spironolactone exists in a subclass of ptoassium-sparing diuretics called aldosterone antagonists. Blocking aldosterone at mineralocorticoid receptors, inhibits potassium secretion and sodium reabsorption in the collecting ducts. Clinical uses: - To reduce potassium loss in a patient receiving a loop or thiazide diuretic - 2nd hyperaldosteronism Key side effects: - Hyperkalemia (risk increased with concurrent use of NSAIDs, BB, and ACE inhibitors - Metabolic acidosis - Gynecomastia - Libido changes (spironolactone) - Nephrolithiasis (triamterene)
What is the most common cause of prerenal injury? What is the treatment?
Prerenal Injury: Hypoperfusion Perfusion is impaired as a result of hypovolemia, decreased CO, systemic vasodilation, renal vasoconstriction, or icnreased intra-abdominal pressure. The is no intrinsic damage ... yet Treatment: - Risk of prerenal azotemia is reduced by maintaining MAP > 65 mmHg and providing appropriate hydration - 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 in intravenous fluid bolus confirms the dx of prerenal azotemia.
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 way.
What steps can be taken to prevent nephrotoxicity from radiographic contrast 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. - Intravenous 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.
What are the key functions of each part of the nephron?
Proximal tubule: - Bulk reabsorption of solutes/water Loop of Henle (descending) -Countercurrent mechanism - high perm. to H2O Loop of Henle (ascending) - Countercurrent mechanism (concentrates urine) - No perm to H2O Distal tubule -Fine tunes solute conc. (aldosterone and ADH) Collecting Duct - Regulates final conc. of urine (aldosterone and ADH)
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 in the urine.
Describe the myogenic mechanism of renal autoregulation.
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 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 = 125 mL/min or ~20% of RBF Filtration fraction is 20%. Means that 20% of the renal blood flow is filtered by the glomerulus and 80% delivered to the peritubular capillaries.
Discuss the anatomy of the renal cortex and medulla.
Renal cortex: outer part of the kidney - contains most part of the nephron (glomerulus, Bowman's capsule, proximal tubules, and distal tubules) Renal medulla: inner part of kidney - contains parts of the nephron not in the renal cortex (loops of henle and collecting ducts) - medulla divided into pyramids - APEX (of pyramid) called papilla. Region contains lots of collecting ducts - Papilla drain urine into minor calyxes - Multiple minor calyces converge to form major calyxes - Major calyces converge to form renal pelvis, empties urine into the ureter. - Calyces, pelvis, and ureters have capability to contract and push urine towards the bladder
Discuss the pathophysiology of renal osteodystrophy
Renal osteodystrophy is caused by: - Decreased vitamin D production - Secondary hyperparathyroidism Pathophysiology: - An inadequate supply of vitamin D impairs calcium absorption in the GI tract. - Body responds to hypocalcemia by increasing parathyroid hormone release. This action demineralizes bone to restore the serum calcium concentration. - Net result is a decreased bone density and increased risk of bone fractures.
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. - Results in tubular obstruction and acute tubular necrosis. - Myoglobin scavenges nitric oxide, leading to renal vasoconstriction and ischemia.
What are the risk factors for halothane hepatitis?
Risk factors: - Age > 40 - Female gender - Greater than 2 exposure - Genetics - Obesity - CYP2E1 induction (alcohol, isoniazid, phenobarbital)
Discuss the use of the aminosteroid NMB in patients with CKD.
Rocuronium primarily undergoes hepatobiliary elimination, 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 to 3-OH vecuronium. Its 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 this population.
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 use evaluate the state of 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 is the function of Kupffer cells?
Since portal vein blood drains the intestine, the liver receives a significant bacterial load. Kupffer cells (part of the reticuloendothelial system) remove the bacteria before the blood drains into the vena cava.
What coagulation factors are NOT produced by hepatocytes?
Since the hepatocytes produce so many proteins, it's easier to learn what they do NOT produce. - Von Willebrand factor: Vascular endothelial cells - Factor III (tissue factor): Vascular endothelia cells - Factor IV (calcium): Diet - Factor VIII (antihemophilic factor): Liver sinusoidal cells (not hepatocytes) and endothelia cells
Discusses glycogenesis, glycogenolysis, and gluconeogenesis. What is the stimulus for each? How does each affect serum glucose?
Stimulus-Metabolic Process-How glucose is normalized Hyperglycemia -> release of: -- Insulin (beta cells) - Glycogenesis - Glucose-> Glycogen (storage) Hypoglycemia -> release of: - Glucagon - Glycogenolysis -> Glycogen (storage) -> Glucose - Epi (adrenal medulla)->Gluconeogenesis-> Non-carbohydrates -> Glucose -- Amino acids --Pyruvate --Lactate --Glycerol (triglycerides) *The liver is an important regulator of serum glucose. Clears insulin from the circulation. Patients with liver failure are at risk of hypoglycemia.
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 of the range of autoregulation. - When 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. Little agreement about range of RBF autoregulation. 50-180 mmHg.
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 time to the R wave on the EKG to minimize the risk of "R-on-T" phenomenon.
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: - SNS - RASS - ADH -- Decrease RBF, GFR, UOP, Na excretion Vasodilation & Sodium Excretion: - Prostaglandins - ANP - Kinins -- Increase RBF, GFR, UOP, Na excretion
What are the 2 modern methods used to classify the severity of acute renal injury?
There are 2 modern methods used to classify the severity of renal injury: - RIFLE Criteria: Risk, Injury, Failure, Loss, ESKD - Acute Kidney Injury Network (AKIN) Both systems grade renal function on serum creatinine and urinary output. Serum creatinine (not urine output) is a more sensitive indicator of renal dysfunction. Both methods highlight that kidney injury occurs along continuum.
Describe the MOA, clinical use, and key side effects of thiazide diuretics.
Thiazide Diuretics: - Hydrochlorothiazide - Metolazone - Indapamide MOA: - Thiazides 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 diabetes mellitus -Hypercalcemia -Hyperuricemia - caution with gouty arthritis - Hypokalemic, hypochloremic metabolic alkalosis - Hypovolemia
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/L) - Urine sodium concentration (130-260 mEq/day) - Urine specific gravity
Compare and contrast the location and function of dopamine 1-and 2 receptors.
Two types of dopamine receptors: DA1 and DA2 - DA1 receptors are present in the kidney and the splanchnic circulation - DA2 receptors are present on the presynaptic adrenergic nerve terminal "----------" -------- DA1 -----------------------DA2 Location - Renal vasculature/tubules - Presynaptic SNS nerve terminal 2nd Messenger - increased cAMP - Decreased cAMP Function - Vasodilation, increased RBF, increased GFR, diuresis, sodium excretion - Decreased NE release
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 contact 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
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. BUN < 8 mg/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
How does uremia affect coagulation? How can bleeding be minimized in these patients?
Uremic patients 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. - The 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 24 hours of surgery.
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. Anticoagulants that are dependent on vitamin K: Proteins S, C, Z
Name 2 tests of hepatocellular injury.
AST (10-40 units/L) and ALT (10-55 units/L) - marked elevation of both suggests hepatitis - AST/ALT ratio > 2 suggest cirrhosis or alcoholic liver disease.
List the absolute and relative contraindications to extracorporeal shock wave lithotripsy.
Absolute contraindications: - Pregnancy - Risk of bleeding Relative contraindications: - Pacemaker/ICD - Calcified aneurysm of the aorta or renal artery - UTI (untreated) - Obstruction beyond the renal stone - Morbid obesity
Where does bilirubin come from? How is it cleared from the body?
Bilirubin: - The erythrocyte's life cycle is 120 days. Aged RBCs are proceeded by the reticuloendothelial cells in the spleen.. - In the spleen: Hgb -> Heme ->Unconjugated bilirubin (this compound is neurotoxic) - Unconjugated bilirubin is lipophilic. It's transported to the liver bound to albumin. - 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.
How do you dose the the reversal agent for the patient with CKD?
Both anticholinesterases and anticholinergics used to reverse NMB undergo renal elimination, and thus share a similar increase in duration. They do not require dosage adjustments.
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. GFR to stage CKD Stage ----- Description ---- GFR mL/min 1 - normal - > 90 2 - mildly decreased - 60-89 3 - moderately decreased - 30-59 4 - severely decreased - 15-29 5 - kidney failure *requires dialysis - < 15
Which class of neuromuscular blockers provides the most predictable duration of action in patients with chronic kidney disease?
Due to their organ independent elimination, cisatracurium and atracurium are more predictable agents in this population.
List 5 indications for dialysis.
Dialysis is the cornerstone of AKI treatment. 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 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, hypoosmolality, hemolysis, and hemoglobinuria (renal failure)
How does chronic kidney disease affect the serum potassium concentration? How is hyperkalemia treated in this patient population?
Hyperkalemia is the result of impaired potassium excretion. Dialysis is indicated when serum potassium exceeds 6 mEq/L Other treatments that reduce serum potassium include: - Glucose (25-50) + insulin (10-20 units) - Hyperventilation (for every 10 mmHg decrease in PaCO2, the serum potassium level is reduced by 0.5 mEq/L) - Sodium bicarbonate (50-100 mEq). - Calcium chloride (1g) does not change serum potassium concentration. It raises threshold potential in the myocardium and reduces the risk of lethal dysrhythmias.
What is the most common complication of dialysis?
Hypotension is the most common event during dialysis. This is due to intravascular volume depletion and osmotic shifts.
What is intrinsic renal injury? What is the treatment?
Intrinsic Injury: Parenchymal - While intrinsic injury can be caused by injury to the tubules, glomerulus, or the interstitial space, we will focus our discussion on acute tubular necrosis. Treatment: - Restore renal perfusion - Supportive
How do the kidneys help to regulate blood pressure? What other systems also contribute to blood pressure regulation?
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) - Intermediate 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 much blood flow do the kidney receive (% of CO and total flow)?
Kidneys receive 20-25% of the CO (1000-1250 mL/min)
Discuss the use of opioids in the patient with chronic kidney disease.
Morphine is metabolized to morphine-6-glucuronide. 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, alfentanil, 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 a reference).
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.
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 - 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 - Sphincter of Oddi controls the flow of bile is released from the common hepatic duct - Contraction of the sphincter of Oddi (narcotics) increases biliary pressure.
How does tubuloglomerular feedback affect renal autoregulation?
The juxtaglomerular apparatus is located in the distal 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.
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. - Lungs excrete volatile acids (CO2) and the kidneys excrete non-volatile acids. - Kidneys maintain acid-base balance by titrating hydrogen in the tubular fluid, which creates acidic or basic urine.
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 trifluoroacetaic acid (TFA). Halothane hepatitis result of immune mediated reaction cause by TFA. 40% metabolized compared to desflurane 0.02% and isoflurane 0.2%. Sevoflurane does NOT produce TFA.
What plasma proteins are produces 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.
What is the functional unit of the liver? Describe its anatomy.
The liver's functional unit is the lobule (otherwise known as the acinus).
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 is hypertension.
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)
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.
What determines how much blood is delivered to the portal vein?
The portal vein receives venous blood that has passed through the splanchnic circulation.