Physiology Review Sheet
Renal Physiology Part II
I.
Water Balance and Agents Affecting Renal Function
a. kidneys maintain water balance via monitoring plasma osmolar concentration in
hypothalamus and ↑ or ↓ ADH release
b. urinary concentration range: very dilute (50 mOsm/L or 1.002 specific gravity) or very
concentrated (1200-1400 mOsm/L or 1.032 specific gravity); Uosm can range from 1/6 of
Posm to 4X Posm
i. note: there’s a greater ability to dilute urine than to concentrate it
ii. response to water load is rapid and efficient
1. initial increase in urine flow rate  due to suppression of ADH (1%
decrease is Posm is necessary to ↓ ADH to 0)
2. ADH suppression is rapid
3. actions of ADH are rapid
iii. as urine flow rate ↑, Uosm ↓
c. ADH
i. entire collecting duct is permeable to water with ADH present
1. water is reabsorbed in all segments
2. produces concentrated urine
3. without ADH, no segment of the CD is permeable to water  excrete lots
of dilute urine (no water reabsorbed and further solute is extracted)
ii. ADH: cys-tyr-phe-gln-asn-cys-pro-arg-gly-NH2 (S-S bond between cys and cys)
1. made in hypothalamus
2. transported down axons of supraoptic and paraventricular nuclei
3. stored in pituitary
iii. stimuli for ↑ release
1. ↑ Posm  osmoreceptors in hypothalamus outside BBB shrink when ECF
osmolarity ↓
2. ↓ BP  baroreceptors (low pressure in great veins and LA and RA; high
pressure in carotid sinus and aortic arch); low pressure receptors are major
regulators of volume effects of ADH (via vagus nerve)
a. clinically: CHF  water retention and hyponatremia are
complications
b. volume depletion at a given Posm  regulation of volume >
regulation of Posm
3. AII
4. pain
5. nausea
6. anesthetics
7. hypoglycemia
iv. inhibitors of release
1. alcohol
2. ANP
3. volume expansion at a given Posm
v. ADH receptors
1. regulate water permeability = V2
a. basolateral surface of CD cells
b. via Gs  ↑ cAMP  ↑ PKA  ↑ protein phosphorylation
c. AQP-2 channels up-regulated rapidly (into apical membrane)
i. ↑ transcription
ii. 6 membrane-spanning domains
d. synthetic ADH analogue (1-deamino-8-D-arg vasopressin – aka
desmopressin – dDAVP)  antidiuretic, but little vasoconstriction
 treat vasopressin deficiency
2. V1 – receptors on smooth muscle of vasculature  vasoconstriction
d. Free Water clearance
i. excretion of water relative to a solute
ii. CH2O = V – Cosm
1. Cosm = (Uosm x V) / Posm
2. Cosm is volume of plasma completely cleared of total solute
iii. solute concentration of urine relative to plasma that determines net loss/gain of
water from body
iv. range
1. + if Uosm < Posm
a. water diuresis
b. dilute urine
c. attempt to concentrate Posm
d. can only form + free water with suppression of ADH
e. ↓ ability to form if . . .
i. ↓ GFR  ↓ solute delivery to AL
ii. ↑ Na+ & water reabsorption  ↓ solute delivery to AL
iii. loop diuretics ↓ + CH2O by inhibiting AL function
iv. thiazides  inhibit DCT function (no effect on medullary
gradient)
v. leads to hypoosmolarity and hyponatremia
f. formed in tAL and TAL (and some in DCT)
2. 0 if Uosm = Posm
a. isosmotic urine
b. isosmotic reduction in ECF
c. promoted by loop diuretics
3. – if Uosm > Posm
a. dehydration
b. concentrated urine
c. attempt to dilute Posm
d. can only be formed with ADH present
e. aka TcH2O  positive number indicating negative free water
clearance
f. formed in CD
g. ↓ ability with anything inhibiting water reabsorption in CD
i. loop diuretics (↓ osmolar gradient)
ii. central diabetes insipidus (problems with ADH synthesis and
release)
iii. nephrogenic diabetes insipidus (problems with ADH acting
on kidney)
iv. water loss in GI tract
v. inappropriate thirst regulation
vi. causes hyperosmolarity and hypernatremia
e. diuretics & aldo sensitive region
II.
i. thiazides, loop diuretics, CA inhibitors  ↑ delivery of Na+ to aldo sensitive
region
ii. block NaCl uptake by macula densa  ↑ renin  ↑ aldo
iii. ↑ secretion of K+ and H+ -- flow dependent (and not all Na+ is reabsorbed)
iv. complications: hypokalemia and metabolic alkalosis  avoid by . . .
1. K+ supplements (and/or bananas)
2. aldo antagonist coadministration (intermittent)
3. interfere with ENaC
f. renal vascular hypertension
i. compromised renal blood flow due to stenosis of renal artery  ↑ renin-angiotensin
cascade  ↑ AII
ii. very sensitive to ACE inhibitors (eg captopril)
1. ↓ BP due to ↑ kinin activity (NOT due to ↓ AII)
2. but could cause collapse of GFR  AII constricts efferent arteriole to
maintain GFR with ↓ blood flow, if remove AII  collapse GFR
iii. AT1 receptor antagonists (e.g. losartan) also ↓ BP (still be careful of effect on
GFR)
g. Darrow-Yannet diagrams
i. defined by changes in ECF
ii. isosmotic dehydration
1. diarrhea or hemorrhage
2. isosmotic ↓ in ECF
iii. hyperosmotic dehydration
1. sweating
2. more water than salt is lost (remember: sweat is hypotonic)
3. osmolarity ↑  water moves from ICF into ECF to make up for ECF lost
iv. hypoosmotic dehydration
1. adrenal insufficiency (Addison’s disease)
2. more salt than water lost (hypotension  ↑ ADH  retain water  ↓
Posm)
3. ICF expands and ECF is reduced
v. isosmotic overhydration
1. edema
2. eg due to liver dysfunction and ↓ albumin  altered Starling forces 
favors filtration into ISF
3. isosmotic expansion of ECF
vi. hyperosmotic overhydration
1. NaCl gain (rare)
2. ↑ osmolality
3. ↓ ICF, but ↑ ECF
vii. hypoosmotic overhydration
1. water gain (SIADH)
2. ↑ ICF and ECF
3. ↓ Posm due to expansion of ECF  triggers release of natriuretic factors
(see prev lecture)
Renal Acid Base
a. pH = - log [H+]
i. arterial = 7.4 ([H+] = 40nM)  normal range = 7.37 – 7.42 ([H+] = 43nM – 38nM)
b. acid inflow
i. volatile acid
1. from CO2 production
a. CO2 + H2O  in RBC via carbonic anhydrase  H2CO3 
dissociates  H+ + HCO3b. CO2 mostly generated in RBC
c. usually transported as HCO3- in plasma (diffuses out of RBC in
exchange for Cl-  anion exchanger, AE1 (aka Band III)
d. reverses in lungs (driven by PCO2 gradients)
2. eliminated by lungs
3. largest amount of acid load
ii. fixed acid
1. metabolism of proteins
a. generates phosphoric acid  phosphate circluates as dibasic form
(HPO42-) at arterial pH (pK = 6.8)
b. first buffer H+, then excrete
2. diet dependent (can be alkaline load with vegetarian diet)
3. eliminated by kidneys
c. H+ buffering
i. prevents ↓ in pH during proton load
ii. bicarbonate
1. NaHCO3 from kidney (24 mEq/L)
2. major buffer
iii. more in acid/base
d. Excretion of acid
i. H+ secretion
1. not a major form of excretion, but acidifies urine
2. in proximal tubule, ↑ H+ by 4-5x  enough to reabsorb 80% HCO3- here
3. NHE-3 (Na/H exchanger in proximal tubule)
4. intercalated cell of CD  abundant H+ ATPase  lots of H+ secretion
ii. HCO3- reabsorption
1. need acidic urine
2. 80% in proximal tubule
a. CA on brush border readily forms CO2  HCO3- diffuses into
interstitium via AE-1 and NBC (no H+ excreted here)
b. note: CA inhibitors only work with tubular CA, not intracellular 
spill Na+ and HCO33. distal nephron – intercalated cells of CD (5%)
a. no CA here  ↑ [H+] in TF forces HCO3- reaction to completion
b. reabsorb all remaining HCO3- of Western diet here
c. if vegetarian (alkalosis)  repolarize intercalated cells to secrete
HCO3- and actively transport H+ into interstitium (takes a few days)
4. 15% reabsorbed in TAL
5. note: no H+ excreted
6. ↑ HCO3- reabsorption
a. volume contraction
b. ↑ filtered load of HCO3c. hypercapnia (↑ PCO2)
d. hypokalemia
e. acidosis (↑ H+ secretion  ↑ HCO3- reabsorption)
7. hyperkalemic metabolic acidosis with alkaline urine
a. K+ moves into cell  significant H+ moves out  ↑ K+ secretion,
↓ H+ secretion  ↓ HCO3- reabsorption
b. kidney responds to IC alkalosis rather than EC acidosis
c. life-threatening  ↑ K+ can alter RMP of excitable cells
i. fix by stimulating Na/K ATPase to ↓ ECF K+
ii. use insulin (+glucose), aldo, NE
iii. titratable acid excretion
1. need acidic urine
2. actually excrete H+
3. depends on pKa and concentration of weak acid
4. phosphate is most abundant weak acid in ECF (3-4 mg%); pKa = 6.8 
good buffer because close to 7.4
a. pH of 7.4  mostly dibasic form  filtered
b. as [H+] ↑ due to tubular secretion  H+ associates with HPO42- 
H2PO4c. excretion of H2PO4  elimination of H+
d. NaHCO3 formed from IC metabolisms  new bicarb created by
kidney  absorbed across basolateral membrane
i. excreted a H+ from protein metabolism
ii. replenished a bicarb from H+ buffering
iv. NH3 production / excretion of NH4+
1. need acidic urine
2. actually excrete H+
3. proximal tubular cells generate NH3  diffuses into tubular lumen as a gas
(non-ionic diffusion)  reacts with H+ to form NH4+ (pKa = 9.0)
a. ammonia is selectively trapped on side where pH is lower
b. lowest pH (in lumen) provides a sink for reaction and NH4+ (ionic)
can’t diffuse back into cell
c. any weak base is trapped in acid urine
d. weak acids are trapped in alkaline urine
i. enhance ASA excretion with OD
ii. administer acetozolaminde (CA inhibitor)
4. NH4+ is reasorbed in TAL  competes with K+ for NaK2Cl co transporter
 secreted into CD by Na/K ATPase on basolateral surface of CD
(unknown why)
5. also forms new bicarbonate (see titratable acid)