1. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Urinary system physiology

2. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Mechanisms of Urine Formation  The kidneys filter the body’s entire plasma volume 60 times each day  The filtrate:  Contains all plasma components except protein  Loses water, nutrients, and essential ions to become urine  The urine contains metabolic wastes and unneeded substances

3. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Glumerular Filtration  The fluid that is forced out of capillaries into the Bowman’s space is called glumerular filtrate  Similar to blood plasma without the proteins  Tubular reabsorption and secretion  The fluid in the DCT and PCT is called tubular fluid  Differs from the filtrate because substances are moving in and out the tubules  Water conservation  Occur in the collecting duct  The fluid is called urine Basic processes of urine formation

4. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Reminder - Capillary Beds of the Nephron  Every nephron has two capillary beds  Glomerulus  Peritubular capillaries  Each glomerulus is:  Fed by an afferent arteriole  Drained by an efferent arteriole

5. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://members.aol.com/Bio50/LecNotes/lecnot37.html  Most molecules smaller than 3 nm can pass freely. That includes water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes and vitamins

6. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Glomerular Filtration  Filtration is a passive process in which hydrostatic pressure forces fluid and solutes through a membrane  The glomerulus is more efficient than other capillary beds because:  Large surface area of the filtration membrane  filtration membrane is more permeable  Glomerular blood pressure is higher because  Arterioles are high-resistance vessels  Afferent arterioles have larger diameters than efferent arterioles  Higher BP results in higher net filtration pressure

7. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Specials characteristics of glumerular filtration  Filtration depends on the balance between hydrostatic pressure and colloid osmotic pressure on both sides of the capillary wall  Blood hydrostatic pressure (BHP) is much higher in the glomerulus (60 mmHg as compared to 10-15)  Hydrostatic pressure in the capsular space is about 18 mm Hg (compared to about 0 in the interstitial fluid).  This is a result of continuous filtration and the presence of fluid in the space.  The colloid osmotic pressure (COP) of the blood is about the same as elsewhere – 32 mm Hg  The glomerular filtrate is almost protein-free and has no significant COP

8. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Glomerular filtration  Total forces in the renal corpuscle:  Forces that work to move fluid from capillaries into capsular space:  Glomerular capillaries hydrostatic pressure (GHP) – 55-60 mm Hg  Forces that work to move fluid out of capsular space to capillaries:  Blood colloid osmotic pressure (BCOP) – 32 mm Hg  Capsular space hydrostatic pressure (CsHP) – 18 mm Hg  60 out – 18 in – 32 in = 10 mmHg net filtration pressure

9. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Net Filtration Pressure Filtration pressure across the filtration membrane is equal to the blood hydrostatic pressure (BHP) minus the colloid osmotic pressure (COP) in the glomerular capillary and minus the capsular pressure (CP).

10. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Glomerular filtration rate (GFR)  Amount of filtrate produced by the two kidneys each minute (~125 ml)  Factors that control GFR:  Total surface area available for filtration  Filtration membrane permeability  Net filtration pressure (NFP)  GFR is usually measured over 24 hr and it is about 180 L/day for males and 150 L/day in females

11. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Regulation of Glomerular Filtration  2 types of mechanisms control the GFR  Renal autoregulation (intrinsic system)  Myogenic mechanism  Tubuloglomerular feedback mechanism  Extrinsic mechanisms  Neural controls (extrinsic system)  Hormonal mechanism (the renin-angiotensin system)

12. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Intrinsic Controls - autoregulation  Renal autoregulation is the ability of the nephron to adjust the blood flow and GFR without external control  Under normal conditions, renal autoregulation maintains a nearly constant glomerular filtration rate  Autoregulation involves two types of control  Flow-dependent tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus  Myogenic – responds to changes in pressure in the renal blood vessels

13. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Tubuluglomerular feedback mechanism  The juxtaglomerular apparatus (JGA) monitors the fluid entering the DCT and adjusts the GFR  Components of the JGA:  The granular/juxtaglumerular (JG) cells – enlarged smooth muscle cells in the afferent arteriole.  They respond to the cells of the macula densa to dilate or constrict the arterioles  Act as mechanoreceptors that sense blood pressure  Can release renin when BP decrease  The macula densa is a patch of ET at the start of the DCT (in some books it said to be in loop of Henle) directly across from the JG cell  Sense NaCl concentration in the tubular fluid

14. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Autoregulation control of GFR  If GFR rises, flow of tubular fluid increases and rate of NaCl reabsorption decreases.  The macula densa sense the change and stimulate the contraction of JG cells  This results in constriction of the afferent arteriole thus reducing GFR

15. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Intrinsic Controls: Myogenic Mechanism  The myogenic mechanism – base on the tendency of smooth muscle to contract when stretches   BP  constriction of afferent arterioles  Helps maintain normal GFR  Protects glomeruli from damaging high BP   BP  dilation of afferent arterioles  Helps maintain normal GFR

16. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Extrinsic Controls – neural control  When the sympathetic nervous system is at rest:  Renal blood vessels are maximally dilated  Autoregulation mechanisms is controlling  Under stress:  Norepinephrine is released by the sympathetic nervous system  Epinephrine is released by the adrenal medulla  Afferent arterioles constrict and filtration is inhibited  The sympathetic nervous system also stimulates the renin- angiotensin mechanism

17. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Renin-Angiotensin Mechanism – hormonal control  A reduction in afferent arteriole pressure triggers the JG cells release renin  Renin acts on angiotensinogen to release angiotensin I  Angiotensin I is converted to angiotensin II  Angiotensin II:  Causes mean arterial pressure to rise  Stimulates the adrenal cortex to release aldosterone  As a result, both systemic and glomerular hydrostatic pressure rise

18. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Extrinsic Controls: Renin-Angiotensin Mechanism  Triggered when the granular cells of the JGA release renin angiotensinogen (a plasma globulin) resin  angiotensin I angiotensin converting enzyme (ACE)  angiotensin II

19. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://www.cvphysiology.com/Blood%20Pressure/BP015.htm

20. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Reabsorption and secretion  Conversion of the glomerular filtrate to urine involves the removal and addition of chemicals by tubular reabsorption and secretion  Accomplished via diffusion, osmosis, and carrier- mediated transport  Cells of the PCT reabsorb 60-70% of the filtrate volume  Reabsorbed materials enter the peritubular fluid and diffuse into the preitubular capillaries

21. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Nonreabsorbed Substances  Substances are not reabsorbed if they:  Lack carriers  Are not lipid soluble  Are too large to pass through membrane pores

22. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Nonreabsorbed Substances  A transport maximum (T m ):  Reflects the number of carriers in the renal tubules available  Exists for nearly every substance that is actively reabsorbed  When the carriers are saturated, excess of that substance is excreted

23. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Regulation of Urine Concentration and Volume  Osmolality  The number of solute particles dissolved in 1L of water  Reflects the solution’s ability to cause osmosis  Body fluids are measured in milliosmols (mOsm)  The kidneys keep the solute load of body fluids constant at about 300 mOsm  This is accomplished by the countercurrent mechanism

24. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The loop of Henle and countercurrent multiplication  Countercurrent multiplication –exchange occurs between fluids moving in different directions; the effect of the exchange increased as the fluid movement continues  Between the close ascending and descending limbs of loop  Difference in permeability in two arms:  Thin descending is permeable to water and almost not to solutes  Thick ascending relatively impermeable to both but contains active transport mechanism that pump sodium and chloride ions from tubular fluid to peritubular fluid of the medulla

25. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Countercurrent multiplication  Sodium and chloride are pumped out of the thick ascending limb into the peritubular fluid by co-transport carriers (Na + -K + /2Cl - transporter)  That elevates the osmotic concentration in the peritubular fluid around the thin descending limb  The result is flow of water out of the thin descending limb into the peritubular fluid and increased concentration of solutes in the thin limb  The arrival of highly concentrated solution in the thick limb accelerate the reabsorption of sodium and chloride ions

26. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 26.13b Countercurrent Multiplication and Concentration of Urine

27. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The countercurrent multiplication:  Creates osmotic gradient in medulla  Facilitates reabsorption of water and solutes before the DCT  Permits passive reabsorption of water from tubular fluid in the collecting system

28. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Osmotic gradient  The kidney has an osmotic gradient from cortex to medulla  The outer layer of the kidney is isotonic with the blood: ~300 milliosmoles/liter  The innermost layer (medulla) is very hypertonic: ~1200 milliosmoles/liter

29. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 26.13c Countercurrent Multiplication and Concentration of Urine

30. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Solutes and water reabsorbed in the medulla need to be returned into circulation.  Blood enters the vasa recta with osmotic concentration of ~300 mOsm/l  Blood descending in the medulla gradually increases in osmotic concentration because of solute reabsorption (plasma proteins limit osmotic flow out of the blood)  Blood flowing toward the cortex gradually decreases in osmotic concentration mainly because of water flowing into capillaries Function of the vasa recta

31. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  DCT performs final adjustment of urine by active secretion or reabsorption  Tubular cells actively reabsorb Na + and Cl -.  In the distal part of the DCT reabsorption of sodium ions in exchange to another cation (usually K+)  The ion pumps and Na+ channels are regulated by aldosterone  The DCT is a primary site of calcium ions reabsorption (regulated by PTH and calcitriol) Reabsorption and secretion at the DCT

32. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The concentration of the urine is adjusted in the collecting ducts  The kidney uses osmosis in the collecting duct to control the concentration and volume of urine  The collecting ducts pass through tissue with a very high osmotic pressure in the medulla.  As the urine passes into the collecting duct it first passes through a region of isotonic osmotic pressure (300 milliosmoles/liter) and then through a region of hypertonic osmotic pressure (up to 1200 milliosmoles/liter)  If the collecting duct has low water permeability the dilute urine in the kidney tubule passes through with little uptake of water  If the collecting duct has high water permeability much of the water will be reabsorbed from the collecting duct into the interstitial fluid

33. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings ADH and urine volume  The permeability of the wall of the collecting duct varies under the influence of antidiuretic hormone (ADH).  ADH is released by the posterior pituitary in response to increased osmotic pressure (decreased water or increased solutes in blood).  When ADH reaches the kidney, it increases the permeability of the epithelial linings of the distal convoluted tubule and collecting duct to water, and water moves rapidly out of these segments, eventually into the blood, by osmosis (water is reabsorbed).  Consequently, urine volume falls, and urine concentrates soluble wastes and other substances in minimal water. Concentrated urine minimizes loss of body fluids when dehydration is likely.  If the osmotic pressure of the blood decreases, ADH is not released and water stays in the collecting duct, leaves as part of the urine.

34. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Aldosterone and urine concentration  Aldosterone is a steroid secreted by the adrenal cortex  It is secreted when blood sodium falls or if blood potassium rises  It is also secreted if BP drops (indirectly through the release of renin-angiotensin II that promotes aldosterone secretion)  Aldosterone secreted – increased tubular reabsorption of Na + in exchange for secretion of K + ions – water follow  Net effect is that the body retains NaCl and water and urine volume reduced  The retention of salt and water help to maintain blood pressure and volume

35. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Atrial natriuretic peptide (ANP) and urine volume  Secreted from the atrial myocardium in response to high BP  Has 4 actions that result in the excretion of more salt and water in the urine:  Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP)  Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion  Inhibits ADH  Inhibits NaCl reabsorption by the collecting ducts

36. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings A Summary of Renal Function Figure 26.16b