Lecture 5

Question 1

Osmotic diuretics

Answer 1

Examples urea or mannitol

These substances, if injected into the bloodstream are filtered and not easily reabsorbed, they draw fluid into the tubules

Question 2

Loop diuretics

Answer 2

Examples furosemide (Lasix), bumetanide (Bumex), ethacrynic acid

So named because they inhibit the Na-2Cl-K co-transporter in the TAL of Henle’s loop
Why does this cause diuresis?
Increased delivery of solutes to the distal tubule due to inhibited reabsorbtion, these solutes act as osmotic agents to draw fluid into the tubule
The countercurrent multiplier system is disrupted and the interstitium cannot become hyperosmolar

Question 3

Thiazide diuretics

Answer 3

Example: hydrochlorothiazide (abbreviated HCTZ)

These agents inhibit sodium chloride reabsorbtion in the early distal tubule.

Question 4

Carbonic anhydrase inhibitors

Answer 4

Example: acetazolamide (Diamox)

Reduce reabsorbtion of Na+ by decreasing bicarbonate reabsorbtion (bicarbonate reabsorbtion is coupled to Na+ reabsorbtion in the proximal tubule via Na+-H+ counter-transport

The disadvantage of this agent is that it causes acidosis through bicarbonate loss in the urine

Question 5

Aldosterone antagonists

Answer 5

Example: spironolactone (Aldactone)

Decreases reabsorbtion of Na+ and decreases K+ secretion by competing for aldosterone binding sites in the distal tubule

Unlike most other diuretics will “spare” potassium

Question 6

Na+ channel blockers

Answer 6

Examples: amiloride and triamterene

Decrease activity of Na/K ATPase in the collecting tubules and thereby decrease Na+ reabsorbtion

These diuretics also “spare” potassium

Question 7

Pre - Renal ARF

Answer 7

Pre-renal- Kidney not getting enough blood flow and therefore becomes ischemic

Examples: heart failure, hypovolemia

Question 8

Intra- Renal ARF

Answer 8

Intra-renal- Damage to the kidney itself

Examples: Toxins, infections, autoimmune disease, direct renal injury

Question 9

Post- Renal ARF

Answer 9

Post-renal- Obstruction of the collecting system

Examples: Stones, urethral valves, tied off ureter, kinked foley

Question 10

Symptoms of Chronic Renal Failure often do not occur until the number of functioning nephrons decreases to at least ____% below normal

Answer 10

70%

Question 11

Mechanisms of injury leading to CRF:

Answer 11

Injury to renal vasculature
Glomerulonephritis
Infection
Nephrotic syndrome

Question 12

Effects of renal failure on the body:

Answer 12

Generalized edema from water and salt retention
Acidosis from failure of the kidneys to excrete acid
High concentrations of nitrogenous waste products (urea, creatine, uric acid) due to failed excretion
Increases in other substances like potassium, phosphates, phenols
Anemia occurs because of decreased synthesis by the kidney of erythropoetin (acts to stimulate RBC production by the bone marrow)
Cardiac output often increases to compensate for decreased oxygen carrying capacity
Pts prone to pulmonary edema and fluid overload’
Minute ventilation is often increased to compensate for acidosis
Osteomalacia:
Abnormal glucose tolerance is common
Platelet and WBC dysfunction occurs
Hypersecretion of gastric acid increases the risk of ulcers
Autonomic neuropathy can slow gastric emptying
Peripheral neuropathy is common

Question 13

Kidney lesions which decrease water and sodium excretion promote _______

Answer 13

HTN!
Hypertension allows water and sodium excretion to return toward normal
Thus the only observed abnormality may be hypertension

Question 14

Basic Principal of Dialysis:

Answer 14

Basic principle:
The artificial kidney passes blood across a thin membrane, on the other side of the membrane is a dialyzing fluid where undesired substances pass by diffusion
The rate of movement of solute across this membrane depends on the concentration gradient of the solute and the permeability and surface area of the membrane and also the length of time the blood and fluid remain in contact with the membrane.
Usually there is about 500 cc of blood in the dialysis machine at any time
To prevent coagulation a small amount of heparin is given

Question 15

Most Common Causes of ESRD:

Answer 15

DM 41%

HTN 28%

Question 16

Indications for dialysis

Answer 16

Fluid overload
Hyperkalemia
Severe acidosis
Metabolic encephalopathy
Pericarditis
Coagulopathy
Refractory GI symptoms
Drug toxicity

Question 17

Normal BUN level:

Answer 17

BUN (blood urea nitrogen) Normally 10-20 mg/dL

Increased BUN can be from decreased GFR or increased protein breakdown (also seen in sepsis or degradation of blood in the GI tract)

Question 18

Normal Creatinine:

Answer 18

Normal values 0.8-1.3 mg/dL in men; 0.6-1.0 in women
A byproduct of muscle metabolism of creatine
Creatinine concentration is directly related to body muscle mass and is inversely related to GFR

Question 19

Creatinine Clearance:

Answer 19

A way to measure GFR
GFR decreases with age in most people (5% decline per decade after age 20)
Because muscle mass also usually declines with age the serum creatinine level remains stable

Question 20

BUN/Creatinine ratio:

Answer 20

Low renal tubular flow rates enhance urea reabsorbtion but do not affect creatinine handling
BUN creatinine ratios > 10:1 are seen in volume depletion or conditions associated with decreased tubular flow and obstructive uropathy

Question 21

Urinalysis:

Answer 21

pH is helpful when arterial pH is known

Urinary pH > 7.0 in the presence of systemic acidosis is suggestive of renal tubular acidosis

Specific gravity is related to urinary osmolality

A specific gravity > 1.018 after an overnight fast is indicative of adequate urinary concentrating ability

A low specific gravity in the face of plasma hyperosmolality is consistent with diabetes insipidus

Question 22

Barbiturates with Renal Failure:

Answer 22

patients with renal disease are more susceptible to these agents probably because of decreased protein binding (more free drug available)

Question 23

Propofol, ketamine, and etomidate with Renal Failure:

Answer 23

no significant differences in uremic patients

Question 24

Benzodiazepines and Renal Failure:

Answer 24

metabolized by liver , most are protein bound so may be additional sensitivity, extra caution with diazepam (Valium) as active metabolites can accumulate

Question 25

Opioids and Renal Failure:

Answer 25

caution is warranted with morphine and meperidine (Demerol), accumulation of metabolites (morphine-6-glucuronide, and normeperidine) can cause problems (respiratory depression and seizures, respectively)

Question 26

Anticholinergics and renal failure:

Answer 26

Atropine and glyco can be used safely though metabolites may accumulate with repeated dosing

Question 27

Metoclopramide and Renal Failure:

Answer 27

Is partly excreted unchanged by the kidney, can accumulate in renal failure but is generally safe to use in a single dose.

Question 28

Volatile agents and renal failure:

Answer 28

There is some concern with enflurane and sevoflurane with fluoride accumulation.

Question 29

Muscle relaxants and renal failure:

Answer 29

Succinylcholine is safe in patients with K<5.0 mEq/L, will transiently increase K+ by almost 0.5 mEq/L Drug of choice is Cis-atracurium as it is degraded by Hoffman elimination Agents to avoid include pancuronium, pipecuronium, alcuronium, doxacurium as these are primarily dependent on renal excretion Vecuronium and rocuronium are primarily eliminated by the liver but there is some mild prolongation in R.F.

Question 30

Reversal agents and renal failure:

Answer 30

Primarily excreted by the kidney but their half-lives are prolonged about as much as some of the muscle relaxants so overall there does not tend to be a problem with these agents.

Question 31

For patients with mild to moderate renal impairment:

Answer 31

Hypovolemia is a key factor in the causation of periop renal failure Post-op renal failure has a mortality of ~50% Prophylaxis with mannitol (0.5g/kg) may help Renal dose dopamine has no good data supporting it at present, in certain cases it can do more harm than good It is easier to treat the complications of fluid overload than it is to treat acute renal failure

Question 32

Risk factors for perioperative renal failure

Answer 32

``` Sepsis Hypovolemia Obstructive jaundice Aminoglycoside antibiotics Nsaids ACE inhibitors Recent dye injections ```

Question 33

Rational management of intraoperative oliguria

Answer 33

First make sure the foley is patent and not kinked Assess fluid status, administer fluid bolus and observe Check CVP and if needed PAC Increase BP if it is low If patient is on lasix they may need their daily lasix if they did not get it Also consider mannitol

Question 34

Kidney Stones:

Answer 34

Most Common: Calcium Oxalate Stones Struvite stones- associated with infection with urea splitting bacteria which form ammonia Most stones <4mm pass spontaneously Analgesics help such as Toradol and opioids Alpha blockers like terazocin may help decrease tone of ureter and promote passage

Question 35

Surgical Mgmt of Kidney Stones:

Answer 35

Used if larger stone or if stone has not passed in 30 days or if there is renal compromise Extracorporeal shock wave lithotripsy (ESWL) Ureteroscopic fragmentation Percutaneous nephrolithotomy Ureteral double J stents (allows urine to drain around obstruction

Question 36

ESWL:

Answer 36

Used for disintegration of stones in the kidney or ureter above the level of the illiac crest Formerly done with patient immersed in water bath. Currently lower energy units require only liquid on the skin to acoustically couple the patient with the energy source. Physics: Tissue has the same acoustic density as water so waves travel through the body without hurting tissue. Impedence by the stone causes it to be broken apart. Tissue damage can occur at the air tissue interface so lung and intestine must be out of the way

Question 37

Contraindications to ESWL:

Answer 37

Inability to properly position patient Pregnancy Infection Obstruction below the level of the stone Proximity to prosthetic device Shock waves are timed 20 ms after the r wave so it is delivered during the ventricular refractory period Pacer/Defibrillators need to be managed per manufacturer directions

Question 38

Gout Tx:

Answer 38

Pain relief: NSAIDs, steroid injection, acetazolamide (works by alkalinizing the urine which traps weak acids) Colchicine was a first line drug, has now fallen out of favor. NSAIDs work better with better safety profile

Question 39

Gout prevention:

Answer 39

Allopurinol: xanthine oxidase inhibitor There is a potential fatal interaction with azathioprine (transplant drug) Uricocurics: Promote excretion of uric acid Examples include sulfinpyrazone and probenecid These drugs compete with uric acid for reabsorbtion at the level of the organic acid transporter in the kidney Caffeine may be protective CPAP may help: Gout associated with sleep apnea (O2 starved cells die and release uric acid)