1. Anatomy and Physiology
Marieb’s Human
Anatomy and Physiology
Ninth Edition
Marieb w Hoehn
Chapter 25
Urinary system
Lecture 16
Part 2: Regulation of Urine Osmolarity and Volume
Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1]
Slides 16 – 38; 50 min [Lecture 2]
118 min (38 slides plus review of course Web sites and syllabus)

2. Where have we been; we are we going?
Renal corpuscle – provides the raw materials to the nephron for processing
PCT – reclaims those substances the body can use
DCT – gets rid of those substances the body doesn’t want or need; reabsorb some more Na+, Ca2+
300 mOsm/L
*Note osmolarity of fluid in PCT
Collecting duct – provides the OPTION of reclaiming H2O or letting it pass out of the body
Obligatory H2O reabsorption…

3. Overview of Facultative H2O Reabsorption
Note that outflow of water from collecting duct is dependent upon the osmotic gradient in the medulla
Figure from: Hole’s Human A&P, 12th edition, 2010
Under influence of ADH
Increasing concentration →
Facultative – not compulsory or automatic
(Facultative water reabsorption)
Urea

4. The Loop of Henle (Nephron Loop)
Crucial renal function is to keep the body fluids at about 300 mOsm (osmolarity of blood plasma) by varying the concentration of urine
The mechanism shown is called the “countercurrent multiplier”
Increasing concentration →
A change of 100 mOsm/L is equivalent to a specific gravity change of about Maximum to which human urine can be concentrated is about 1200 mOsm/L (roughly a specific gravity of 1.030)
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001
SO HOW DOES THIS HELP?

5. The Countercurrent Multiplier
Recall that all movement of H2O occurs passively by osmosis
We would like some mechanism to concentrate urine
Excrete more H2O when body fluids are tending to become hypotonic (more dilute)
Excrete less H2O when body fluids are tending to become hypertonic (more concentrated)
Utilizes two factors
Hypertonicity of the peritubular fluid, established by the countercurrent multiplier
Variable permeability of the collecting ducts to H2O depending upon levels of ADH
We will use the phrase, “Water follows salt (solute) when it can”

6. Influence of ADH on H2O Reabsorption
Note that amount of water pulled out of collecting duct is dependent upon the osmotic gradient in the medulla that was established by the countercurrent multiplier.
Under influence of ADH
Figure from: Hole’s Human A&P, 12th edition, 2010
Facultative – not compulsory or automatic
(Facultative water reabsorption)
Urea

7. Vasa Recta of Juxtamedullary Nephrons
Figure from: Hole’s Human A&P, 12th edition, 2010
Recall that the vasa recta is present in juxtamedullary nephron loops (which give the kidneys the ability to produce a concentrated urine)
The vasa recta functions to
Deliver blood to medullary cells
Return reabsorbed solutes and water in the medulla to the general circulation without disrupting the medullary concentration gradient

8. Urea and Uric Acid Excretion
product of amino acid catabolism (deamination)
plasma concentration reflects the amount or protein in diet
enters renal tubules through glomerular filtration
50% reabsorbed
rest is excreted
Uric Acid
product of nucleic acid metabolism
enters renal tubules through glomerular filtration
100% of filtered uric acid is reabsorbed
10% secreted and excreted

9. Summary of Events in the Nephron/Collecting Duct
Filtrate produced
Reabsorption of 65% of filtrate
Obligatory water reabsorption
Reabsorption of Na+ and Cl- by active transport
5,6. Facultative reabsorption of water
7. Absorption of solutes and water by vasa recta
(Aldosterone)
(Aldosterone)

10. Diuretics Osmotic diuretics, e.g., mannitol, glucose
A diuretic promotes the loss of water in the urine
Osmotic diuretics, e.g., mannitol, glucose
Drugs that block Na+/Cl- transport in PCT and DCT, e.g., hydrochlorothiazide
High-ceiling/loop diuretics that reduce gradient along nephron loop, e.g., furosemide (Lasix)
Aldosterone-blocking agents, e.g., spironolactone (K+ sparing), natriuretic peptides
ACE inhibitors, e.g., Captopril
Drugs with diuretic side-effects, e.g., alcohol (how?), caffeine
Caffeine dilates afferent ateriole and increases GFR, thus causing diuresis.

11. Review Regulation of urine concentration and volume Urine composition
Results from a combination of
Countercurrent multiplier in loop of Henle
Responsiveness of the DCT and collecting ducts to ADH and aldosterone
Is critical to homeostasis
Urine composition
Is variable
Depends upon both diet and activity
Consists of mostly water plus
Creatinine
Urea
Uric acid
Traces of amino acids
Electrolytes

12. Effect of ADH on Renal Tubules
without ADH, DCT and collecting duct are impermeable to water
with ADH, DCT and collecting duct become permeable to water
with ADH, water is reabsorbed by osmosis into hypertonic medullary interstitial fluid via aquaporin channels in tubular cells
What has to happen as far as osmolarity in the DCT in order for the kidney to have the option to reabsorb water under the influence of ADH?
Figure from: Hole’s Human A&P, 12th edition, 2010

13. Ability to Concentrate Urine in Other Species
Animal Max. Urine Conc. (mOsm /L)
Beaver Pig 1,100
Human 1,400
Dog 2,400
White Rat 3,000
Kangaroo Mouse ,000
Australian Hopping Mouse ,000
Table/data from:

14. Renal Clearance
the rate (ml/min) at which a substance is removed from the plasma
tests of renal clearance (Cx)
inulin clearance test (standard; 125 ml/min)
creatinine clearance test (easy to do)
paraminohippuric acid (PAH) test
tests of renal clearance are used to calculate glomerular filtration rate
Creatinine is used because it fulfills these requirements (though not perfectly) and it is produced naturally by the body (creatinine is a metabolite of creatine, which is found in muscle). It is actively secreted by the kidneys such that creatinine clearance overestimates actual GFR by 10-20%. This margin of error is acceptable considering the ease with which creatinine clearance is measured. Other more precise GFR measurements involve constant infusions of inulin or another compound, to maintain a steady state in the blood. Since creatinine is already at a steady-state concentration in the blood, measuring creatinine clearance is much less cumbersome.
Examples: - Cx = 125 ml/min (125 ml of ‘x’ is removed from the plasma every min = 100%) - Cx = 60 ml/min (some reabsorption of ‘x’ is occurring) - Cx = 0 ml/min (complete reasbsorption of ‘x’ is occurring) - Cx = 630 ml/min (secretion of ‘x’ is occurring)