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

2. Hydrostatic Pressures n 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) n 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) - CHP is normally low (15 mm Hg) Thus, net hydrostatic pressure = 50 - 15 = 35 mm Hg

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

4. Net Filtration Pressure n Thus, the net filtration pressure = net hydrostatic pressure - colloid osmotic pressure = 35 mm Hg - 25 mm Hg = 10 mm Hg n 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

6. Regulation of the Urinary System Endocrine Regulation of Kidney Function Autoregulation of Kidney Function Neural (sympathetic) Regulation of Kidney Function Urine Flow

7. Endocrine Regulation of Kidney Function n n Endocrine Glands: ductless glands which secrete hormones into the circulation, acting at a distant site n n Three main hormones are involved in regulation of kidney functions: - Antidiuretic Hormone (ADH, AVP) - Aldosterone - Renin, Angiotensin II

8. Antidiuretic Hormone n n Now called arginine vasopressin (AVP) n n Synthesized in the brain, released from posterior pituitary n n Action: increases permeability of the distal convoluted tubule and collecting ducts to water n n Result: - increased water reabsorption - decreased urine volume - decreased osmolality of interstitial fluids

9. Antidiuretic Hormone Regulation of ADH/AVP secretion: n n Response to osmolality of interstitial fluid: - Osmoreceptors in the brain detect changes in osmolality - Increased osmolality results in increased ADH release - increased water reabsorption - decreased osmolality of fluids - Decreased osmolality results in decreased ADH release - decreased water reabsorption - increased osmolality of fluids

10. Antidiuretic Hormone Regulation of ADH/AVP secretion: n n Response to changes in blood pressure: - Blood pressure receptors in heart, aortic arch, and carotid artery - Increased blood pressure results in decreased ADH - decreased water reabsorption - decreased blood volume, blood pressure - Decreased blood pressure results in increased ADH - increased water reabsorption - increased blood volume, pressure

11. Antidiuretic Hormone n n ADH also inhibited by alcohol, caffeine - decreased water reabsorption - increased urinary volume - potential for dehydration n n Insufficient ADH results in disease: diabetes insipidus - impaired water reabsorption from DCT, collecting ducts - increase urine volume 10 times

12. Aldosterone n n Steroid hormone produced in the adrenal cortex n n Stimulates sodium and chloride uptake from DCT and collecting duct n n Increases expression of genes involved in active sodium transport n n Since Cl- ions follow Na+ ions, also get increased resorption of chloride n n Since Na+ transport out of nephron is linked to K+ transport into nephron, aldosterone increases urinary potassium content

13. Aldosterone n n Thus, decreased aldosterone secretion results in decreased reabsorption of Na+ and Cl-, with increased secretion of K+ - increased osmolarity of urine, loss of sodium - decreased gradient for water reabsorption in the DCT and collecting tubule (increased water loss)

14. Regulation of Aldosterone Secretion n n Aldosterone is regulated primarily by levels of Na+, K+, and angiotensin II (see next slide) n n Decreased [Na+] and increased [K+] in interstitial fluid of adrenal cortex results in increased aldosterone secretion - increased reabsorption of Na+, secretion of K+ n n Increased [Na+] and decreased [K+] in interstitial fluid leads to decreased aldosterone secretion - decreased reabsorption of Na+, secretion of K+

15. Renin/Angiotensin System n n Blood pressure (and aldosterone secretion) is also regulated by interactions between renin and angiotensin n n Renin is produced by the juxtaglomerular apparatus of the kidney n n Regulation: renin increases if blood pressure at the afferent arteriole decreases, or if sodium concentrations in the DCT decrease

16. Action of Renin/Angiotensin System n n Action: renin converts angiotensinogen to angiotensin I n n Angiotensin I is converted to angiotensin II n n Angiotensin II increases blood pressure

17. Renin/Angiotensin System n n Angiotensin II increases blood pressure two ways: - Vasoconstriction (decreased diameter of vessels) - Increased aldosterone release - aldosterone increases salt reabsorption - increased osmolality of interstitial fluids - results in increased ADH secretion, increased water reabsorption - end result = increased blood pressure

18. Autoregulation of Kidney Function n n If systemic blood pressure (BP) decreases, the afferent arteriole will relax (expand) to allow more blood into the glomerular capillaries n n If systemic BP increases, the afferent arteriole can constrict to prevent excessive glomerular pressure n n In addition, constriction of the efferent arteriole increases glomerular pressure n n Relaxation of the efferent arteriole decreases glomerular pressure

19. Autoregulation of Kidney Function n n Through regulation of afferent and efferent arteriole constriction, the glomerular hydrostatic pressure can be maintained over a wider range of blood pressures n n Upper limit: systemic BP of 180. Above this, hydrostatic BP increases, resulting in damage to the kidneys

20. Sympathetic Regulation of Kidney Function n n The kidneys receive neural input from sympathetic fibers n n Neurotransmitter: norepinephrine n n Action: constriction of small arteries and afferent arterioles n n Severe stress or injury causes decreased renal blood supply and decreased glomerular hydrostatic pressure, resulting in markedly decreased filtration rates and tissue damage n n The result of sustained shock: kidney failure

21. Tubular Load & Tubular Maximum n n Tubular Load: the total amount of a substance that passes through the filtration membrane per minute n n Tubular Maximum: the maximum rate at which a substance can be reabsorbed n n Example: tubular maximum of glucose is 320 mg/min In diabetics, this maximum is exceeded, resulting in glucose in the urine.

22. Urine Flow: Kidneys to Bladder n n Flow from the kidney to the bladder requires peristaltic contraction of the ureters - hydrostatic pressure at renal pelvis = 0 - contractions increased by parasympathetic innervation - contractions occur every few seconds to minutes

23. Urine Flow: Micturition n n Micturition: release of urine from the bladder n n Mechanism: micturition reflex - stretch receptors in bladder wall cause parasympathetic firing - bladder wall contracts - internal urinary sphincter relaxes (smooth muscle) - external sphincter required to control timing of micturition