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)

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…

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

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 0.0025. 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?

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”

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

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

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

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)

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.

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

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

Ability to Concentrate Urine in Other Species Animal Max. Urine Conc. (mOsm /L) Beaver 500 Pig 1,100 Human 1,400 Dog 2,400 White Rat 3,000 Kangaroo Mouse 6,000 Australian Hopping Mouse 10,000 Table/data from: www.profelis.org/neu/ppt-d/gh_kapitel_028.ppt

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)