Name the mechanism of transport, disease and diuretic that occurs at the following nephron sites:

1. Proximal tubule
2. Thick ascending limb
3. Distal convoluted tubule
4. Cortical collecting tubule and duct

1. Sodium-hydrogen exchanger (NHE); no disease; affected by carbonic anhydrase inhibition indirectly
2. Sodium-Potassium-Chloride transporter (NKCC); Bartter's syndrome; blocked by loop diuretics
3. Sodium-chloride co-transporter (NCCT): Gitelman's syndrome; blocked by thiazides
4. Epithelial sodium channel (ENaC); pseudohypoaldosteronism, blocked by ENaC blockers and indirectly blocked by aldosterone antagonists

Channels = passive transport, no chemical reaction between channel and molecule in flux. Faster than transporter movement

Transport= active or passive

Paracellular is always passive; only requires movement across one barrier

Transcellular entails movement across two barriers; can be passive OR active

U/P Na ratio x P/U Creatinine ratio

1. Erythropoietin - interstitial cells of kidney
2. 1,25 (OH)₂ vitamin D - proximal tubular cells
3. Renin - granular cells of JG apparatus
4. Klotho- newly discovered; mainly found in distal convoluted cells

Drug avoids renal absorption by binding to albumin; enters tubule via anion transporter, where it inhibits NK2C in thick ascending limb of loop of Henle. This abolishes hypertonicity of medulla, preventing concentration of urine.

Ethacrynic is ideal, although torsemide might also be viable. Do NOT give furosemide or bumetanide.

Used when patient is losing GFR and other salt retaining pathology (e.g. CHF, cirrhosis, pulmonary edema, nephrotic syndrome)

Proteinuria will inactivate diuretic activity in the tubule (albumin binds to diuretic, deactivating it)

They cause release of prostaglandin from macula densa, leading to systemic vasodilation.

Ethacrynic acid has a high incidence of ototoxicity (although all loop diuretics can cause it)

Increased renin-aldosterone stimulates excretion of potassium.

Amiloride, a potassium-sparing diuretic. Blocks sodium channels in the cortical collecting ducts.

1. Inhibits water reabsorption throughout nephron; inhibits Na reabsorption at sights of paracellular Na reabsorption (i.e. thick ascending limb of Henle, proximal tubule)
2. Reduce bicarb reabsorption at proximal tubule and thick ascending limb of Henle. Reduce hydrogen ion secretion in cortical collecting duct.

1. All diuretics cause volume (expansion/depletion)
2. All diuretics cause secondary (hyper/hypo)aldosteronism and (increased/decreased) delivery of sodium to the collecting duct. This results in (hypo/hyper)kalemia, except in the case of _____.
3. Most diuretics cause metabolic (acidosis/alkolosis), with the exception of carbonic anhydrase inhibitors, which cause (acidosis/alkolosis). What is the mechanism for the former?

1. Depletion
2. Hyperaldosteronism, increased, hypokalemia, K⁺-sparing diuretics
3. Alkolosis, acidosis. Volume depletion and potassium loss.

1. Those affecting the proximal tubule. The volume depletion in the other agents cause urate reabsorption in the proximal tubule.
2. Those acting on the proximal tubule and loop diuretics (the former for the same reason above, the latter because loop diuretics inhibit Ca reabsorption at the loop of Henle); thiazides have the most pronounced hypocalcuria.
3. Increase excretion (loop diuretics inhibit absorption at loop of Henle, thiazides inhibit at distal convoluted tubule)

1. Aldosterone antagonists (spironolactone and eplerenone) = cytoplasmic mineralocorticoid receptors
2. Epithelial sodium channel blockers (triamterene and amiloride) = luminal membrane of the cortical collecting duct

Autosomal dominant genetic overexpression of ENaC.

ENaC blockers (triamterene and amiloride) can be used to block it, but since aldosterone is already low, spironolactone and eplerenone are ineffective.

You take a urine sample of a patient with hypokalemia. What would you expect if the urine potassium was...

1. Low
2. Normal

1. Low intake, GI loss, intracellular shift
2. Renal loss ("normal" excretion during hypokalemia is considered inappropriately high excretion)

1. ß2-adrenergic agonists & insulin (act on Na/K pump), alkalosis 
2. Acidic pH (note: minimal movement with organic or respiratory acidosis)

Diabetic nephropathy and interstitial diseases of different causes. Patient will most likely be hypertensive with moderate to mild renal insufficiency

Primary renal salt reabsorption proximal to collecting duct (mechanism unknown) --> Low renin --> Low aldosterone --> hyperkalemia, metabolic acidosis

Hyper = Cardiac arrythmias, increased velocity of repolarization, T waves peaked with shorter QT intervals, narrowed QRS, loss of P waves

Hypo = ST depression, T wave inversion, U wave appears

A patient has hyperkalemia. What would the following scenarios suggest?

1. Low PRA, low aldosterone, high BP
2. High PRA, high aldosterone, low BP
3. High PRA, high aldosterone, high BP

1. Hyporeninemic hypoaldosteronism (due to diabetic nephropathy or interstitial disease), pseudohypoaldosteronism type II / Gordon's (enhanced reabsorption of Na, decreased flow rate)
2. Pseudohypoaldosteronism type I (aldosterone is ineffective)
3. Drug-related (amiloride/triamterene, antibiotics)

What lab values would you expect for the following conditions?

1. Primary hyperaldosteronism
2. Apparent mineralcorticoid excess state
3. Liddle's syndrome
4. Addison's disease
5. Dexamethasone-suppressible hyperaldosteronism

1. Low renin, high aldosterone, low K, high BP
2. Low renin, low aldosterone, low K, high BP (defect in ß-hydroxysteroid dehydrogenase)
3. Low renin, low aldo, low K, high BP (overexpression of ENaC)
4. High renin, low aldosterone, high K, low BP
5. Low renin, high aldosterone, low K, high BP

All conditions have high renin and high aldosterone

1. Renal salt loss - low K, low BP
2. Increase in renin without volume depletion (malignant hypertension or renal artery stenosis) - low K, high BP
3. Low salt intake - normal K, high BP

1. Intravenous calcium (stabilizes cell membrane)
2. Insulin with glucose (stimulates intracellular shift)
3. Intestinal K-binding with cation-exchange resin and/or dialysis
4. Increased renal excretion with diuretics (provide adequate Na and mineralocorticoids)

What are important clinical findings for:

1. ATN
2. Acute glomerulonephritis
3. Acute interstitial nephritis
4. Urethral obstruction
5. Obstructive uropathy

1. Dirty granular casts in urine
2. Cellular casts
3. Cellular casts and eosinophils
4. Distended bladder, anuria
5. Hydronephrosis/ureter on renal sonogram; anuria

PRERENAL vs. ATN

1. Urine specific gravity: >1020 vs. <1012
2. Urine/plasma creatinine: >40 vs. <20
3. Urine sodium: <20 vs. >40
4. FE_Na: <1% vs. >2%
5. FE_Urea: <35% vs. >50%

Efferent arteriolar tone is greater than afferent, maintaining GFR (and filtration fraction) in face of reduced renal blood flow.

In ATN, the opposite is true: afferent constriction is greater than efferent, leading to progressive loss of GFR and filtration fraction

1. Parasympathetic (S2-S4) innervate the bladder body, causing contraction. Carried by pelvic nerve
2. Afferent axons return through the pelvic nerve
3. Sympathetic nerves from T10-L2 innervate bladder body, neck and prostatic urethra, causing relaxation. Carried by hypogastric nerve
4. Somatic nerves are innervating the external sphincter originate from S2-S4 and travel through the pudendal

Parasympathetic are inhibited (bladder body relaxes)

Sympathetics stimulate bladder neck contraction via alpha-adrenergic receptors and relaxes bladder body via ß-receptors

Pudendal contracts external sphincter

What are the consequences of neurological damage...

1. Above the brainstem?
2. At the suprasacral (above T12) lesion?
3. Below the sacral segment or at the pelvic nerve?

1. Involuntary bladder contraction and synergic relaxation of sphincter. Causes incontinence with complete bladder emptying at low pressure. No renal function at risk.
2. Detrusor hyperreflexia with external sphyncter dyssynergia; high bladder pressure dangerous to renal function and hydronephrosis
3. Areflexic bladder

What is the drug therapy of choice for...

1. Detrusor hypersensitivity
2. Obstruction due to prostate hyperplasia

1. Anticholinergic
2. Alpha-adrenergic blockers (terazosin, doxazosin, tamsulosin)

DHT (testosterone converted by 5-alpha-reductase in prostate) and estrogen. Low testosterone/estrogen ratio.

Note: no clear relationship between size of prostate and symptoms

• Acute urinary retention
• Chronic urinary retention
• Life-threatening urinary tract infections
• Evidence of bladder or kidney damage

1. TURP (transurethral resection of prostate), open surgery for extremely large
2. 5-alpha-reductase inhibitors (finasteride/dutasteride) and alpha-adrenergic blockers (doxazosin, tamsolosin, solodosin). Note: more specific alpha blockers that target 1a = less orthostatic hypotension

Cystitis = frequrency, dyuria and hypogastric pain; NO FEVER. 3-day course of anti-microbial

Pyelonephritis = flank pain and systemic symptoms (fever, chills, malaise, leukocytosis). 7-14 days course treatment

Neisseria gonorrhoeae or Chlamydia trachomitis; Escherichia coli

In both cases, believed to be upstream complication of UTI; usually associated with prostatic enlargement.

• Phentolamine: alpha-adrenergic blocker (used in catecholamine excess)
• IV nitroglycerine: can lead to methemoglobinemia and cyanide accumulation
• Esmolol: ß-1 selective adrenergic block
• Fenoldopam: dopamine agonist, vasodilator

Thiazides will decrease calcium excretion (volume depletion increases AngII, and consequently, increases Na reabsorption in proximal tubule via Na/H pump; calcium follows sodium via paracellular route)

Thiazide will increase magnesium excretion

Increase calcium excretion (NKCC inhibition prevents paracellular calcium reabsorption; counters effect of low EVV)

Thiazides decrease calcium excretion (low extracellular volume increases AngII --> increases Na/H activity --> increases Na reabsorption in proximal tubule --> increases calcium reabsorption in positive tubule)