Physiology of the Urinary System

1. Physiology of the Urinary System Functions of the Urinary System Major Nitrogenous Wastes Formation of Urine Filtration Reabsorption Secretion

2. Functions of the Urinary System • Remove waste products from blood • Maintain water balance • Maintain salt balance • Regulate blood pressure

3. Major Nitrogen-containing Wastes • Urea: results from catabolism of amino acids - amino acids => ammonia => urea - protein is 16% nitrogen - 100 g of protein => 16 g of waste nitrogen - of these 16 g, 14 g is converted to urea - most abundant nitrogenous waste product (21 g/day) • Ammonia salts: Minor component of urine. Of 16 g of waste nitrogen, 2 g are converted to ammonia salt

4. Major Nitrogen-containing Wastes (cont.) • Uric acid: results from breakdown of nucleic acids (RNA), about 0.5 g/day • Creatine: generated in muscle tissue from breakdown of creatine phosphate (1.8 g/day, depending on muscle mass)

5. Processes involved in Urine Formation Three processes are involved: • Filtration: forcing water and solutes across plasma membrane (renal corpuscle). Selection by size. • Reabsorption: Taking back water and important solutes (nutrients, salts) back into the bloodstream. Very specific. • Secretion: Transporting substances into urine. Specific.

7. parietal epithelium efferent arteriole podocyte DCT macula densa glomerular capillary juxtaglomerular cells afferent arteriole Filtration • All filtration occurs at the renal corpuscle • Recall that the corpuscle if formed from the glomerulus (capillary) and Bowman’s capsule (continuous with the tubules of the nephron)

8. Process of Filtration • Blood pressure forces water across the glomerular endothelium, basement membrane, and filtration slits of podocyte cells (visceral layer of Bowman’s capsule) into the capsular space filtration Podocytes filtration slits fenestra capsular space endothelial wall of capillary basement membrane

10. Size Selection at Different Components of Filtration Apparatus • Fenestrated capillaries of glomerulus: pores allow water and most solutes through (but NOT blood cells) • Basement membrane: permits smaller proteins, nutrients, and ions through • Filtration slits of podocytes: prevent passage of most proteins - The filtrate contains dissolved ions and small organic molecules, including nutrients. - Filtration is selective for size only

11. Some Definitions regarding Filtration • Renal Fraction: that part of the total cardiac output which passes through the kidneys (about 20%) • The renal flow rate is 1.2 liters of blood per minute • Filtration Fraction: the amount of plasma going to the kidney which is filtered and becomes filtrate - on average, 20% of renal fraction - blood is about 50% plasma, so the renal flow rate is 0.6 liters/min - 0.6 liters/min x 20% = 0.12 ml filtrate/min

12. Some More Definitions regarding Filtration • Glomerular Filtration Rate: how much filtrate is produced per minute (120 ml/min, or 170 liters/day) - about 99% of this must be reabsorbed - urine output = 1.7 liters

13. Driving Force of Filtration • The filtration across membranes is driven by the net filtration pressure • The net filtration pressure = net hydrostatic pressure minus the net colloid osmotic pressure • The net hydrostatic pressure is determined by the glomerular hydrostatic pressure (GHP) minus the capsular hydrostatic pressure (CHP)

14. Hydrostatic Pressures • The GHP is the blood pressure in the glomerular capillaries - tendency to push water and solutes out of plasma, across membranes - since efferent arteriole is smaller than afferent arteriole, GHP is relatively high (50 mm Hg) • The CHP is the resistance to flow along nephron tubules and ducts - tendency to push water and solutes out of filtrate, into plasma - CHP is normally low (15 mm Hg) Thus, net hydrostatic pressure = 50 - 15 = 35 mm Hg

15. Colloid Osmotic Pressure (COP) • The colloid osmotic pressure is the osmotic pressure resulting from the presence of proteins in a solution • The COP of blood is about 25 mm Hg • The COP of filtrate is normally 0 • Thus, total COP is 25 mm Hg

16. Net Filtration Pressure • Thus, the net filtration pressure = net hydrostatic pressure - colloid osmotic pressure = 35 mm Hg - 25 mm Hg = 10 mm Hg • Abnormal changes in either net hydrostatic pressure or colloid osmotic pressure will affect filtration rate - damage to glomerulus will allow proteins into the filtrate, decreasing net COP, and increasing filtration rate - increasing capsular hydrostatic pressure (obstruction of tubules, ducts) will markedly decrease net hydrostatic pressure, decreasing filtration rate

17. Reabsorption • Reabsorption takes place in the proximal convoluted tubule (PCT; 65%), loop of Henle (20%), distal convoluted tubule (DCT; 5%), and collecting ducts (10%) • In the PCT: - Over 99% of organic nutrients (glucose, amino acids) are resorbed - Active ion resorption - Water resorption by osmosis - Other solvents (urea, lipids, Cl- ions) resorbed by solvent drag • At the end of the PCT, filtrate contains no glucose, no amino acids, 12% of NaCl, 25% of volume, and increased urea, uric acid (no change in osmolarity)

18. Resorption in the Loop of Henle • In the loop of Henle, half of the remaining water and 2/3rds of the remaining NaCl will be resorbed • The loop of Henle utilizes a countercurrent multiplication exchange system to reabsorb water and NaCl • Countercurrent: exchange occurs between fluids moving in opposite directions • Multiplication: the effect of exchange between the limbs increasing as fluid movement occurs

19. Countercurrent Exchange: Loop of Henle • The walls of the descending and ascending limbs have different permeability characteristics • The descending limb is permeable to water, impermeable to solutes • The ascending limb is impermeable to water and solutes • Na+ and Cl- are actively pumped out of ascending limb • Osmotic concentration of peritubular fluid rises • Water leaves descending limb by osmosis • Increased solute concentration causes increased Na+ and Cl- transport

20. Results of Countercurrent Exchange • Get resorption of water and NaCl, with filtrate at the end of the loop of Henle with lower osmolarity than at the beginning of the loop • A concentration gradient is built up in the peritubular space, which allows subsequent resorption of water from collecting duct

21. Reabsorption in the DCT and Collecting Ducts • In the distal convoluted tubule, small adjustments in composition of filtrate take place - active transport of Na+ and Cl- continues - water reabsorption occurs under influence of ADH (5% of total water reabsorption) • In the collecting ducts, water and sodium are reabsorbed - water is reabsorbed under regulation by ADH (10% of water reabsorption) - sodium reabsorbed under regulation by aldosterone - some reabsorption of bicarbonate and urea

22. Secretion into Urinary Filtrate • Secretion plays a relatively small role in production of urine • Occurs in tubules and ducts • There is active secretion of a number of substances into the filtrate: - potassium, hydrogen ions (in exchange for sodium ions) - creatinine, penicillin, neurotransmitters, organic acids and bases

23. Summary • Reviewed major nitrogenous wastes • Defined terminology related to filtration • Reviewed processes of filtration, absorption, and secretion (mechanisms, site of action)

24. Next Lecture...... Regulation of the Urinary System