1. Renal Physiology For Bio 260

2. Review Your Anatomy!!!

3. Figure 25.1 Esophagus (cut) Inferior vena cava Adrenal gland Hepatic veins (cut) Renal artery Renal hilum Renal vein Iliac crest Kidney Ureter Urinary bladder Urethra Aorta Rectum (cut) Uterus (part of female reproductive system)

4. Figure 25.3 Renal cortex Renal medulla Major calyx Papilla of pyramid Renal pelvis Ureter Minor calyx Renal column Renal pyramid in renal medulla Fibrous capsule Renal hilum (a) Photograph of right kidney, frontal section(b) Diagrammatic view

5. Figure 25.4b Aorta Renal artery Segmental artery Interlobar artery Arcuate artery Cortical radiate artery Afferent arteriole Glomerulus (capillaries) Nephron-associated blood vessels (see Figure 25.7) Inferior vena cava Renal vein Interlobar vein Arcuate vein Cortical radiate vein Peritubular capillaries and vasa recta Efferent arteriole (b) Path of blood flow through renal blood vessels

6. Nephrons Structural and functional units that form urine ~1 million per kidney Two main parts 1.Glomerulus: a tuft of capillaries 2.Renal tubule: begins as cup-shaped glomerular (Bowman’s) capsule surrounding the glomerulus

7. Figure 25.5

8. Fenestrated endothelium of the glomerulus Microvilli Cortex Medulla Podocyte Basement membrane Mitochondria Highly infolded plasma membrane Proximal convoluted tubule Distal convoluted tubule Descending limb Loop of Henle Ascending limb Glomerular capsule Renal corpuscle Glomerulus Thick segment Collecting duct Intercalated cell Principal cell Thin segment Proximal convoluted tubule cells Glomerular capsule: parietal layer Glomerular capsule: visceral layer Distal convoluted tubule cells Loop of Henle (thin-segment) cells Collecting duct cells Renal cortex Renal medulla Renal pelvis Ureter Kidney

9. Nephrons Cortical nephrons—85% of nephrons; almost entirely in the cortex Juxtamedullary nephrons – Long loops of Henle deeply invade the medulla – Extensive thin segments – Important in the production of concentrated urine

10. Juxtaglomerular Apparatus (JGA) Granular cells (juxtaglomerular, or JG cells) – Enlarged, smooth muscle cells of arteriole – Secretory granules contain renin – Act as mechanoreceptors that sense blood pressure

11. Juxtaglomerular Apparatus (JGA) Macula densa – Tall, closely packed cells of the ascending limb – Act as chemoreceptors that sense NaCl content of filtrate Extraglomerular mesangial cells – Interconnected with gap junctions – May pass signals between macula densa and granular cells

12. Figure 25.8 Glomerulus Glomerular capsule Afferent arteriole Efferent arteriole Red blood cell Podocyte cell body (visceral layer) Foot processes of podocytes Parietal layer of glomerular capsule Proximal tubule cell Lumens of glomerular capillaries Endothelial cell of glomerular capillary Efferent arteriole Macula densa cells of the ascending limb of loop of Henle Granular cells Extraglomerular mesangial cells Afferent arteriole Capsular space Renal corpuscle Juxtaglomerular apparatus Mesangial cells between capillaries Juxtaglomerular apparatus

13. Renal Physiology

14. Kidney Functions Removal of toxins, metabolic wastes, and excess ions from the blood Regulation of blood volume, chemical composition, and pH

15. Kidney Functions Gluconeogenesis during prolonged fasting Endocrine functions – Renin: regulation of blood pressure and kidney function – Erythropoietin: regulation of RBC production Activation of vitamin D

16. Kidney Physiology: Mechanisms of Urine Formation The kidneys filter the body’s entire plasma volume 60 times each day Filtrate – Blood plasma minus proteins Urine – <1% of total filtrate – Contains metabolic wastes and unneeded substances

17. Mechanisms of Urine Formation 1.Glomerular filtration 2.Tubular reabsorption – Returns all glucose and amino acids, 99% of water, salt, and other components to the blood 3.Tubular secretion – Reverse of reabsoprtion: selective addition to urine

18. Figure 25.10 Cortical radiate artery Afferent arteriole Glomerular capillaries Efferent arteriole Glomerular capsule Rest of renal tubule containing filtrate Peritubular capillary To cortical radiate vein Urine Glomerular filtration Tubular reabsorption Tubular secretion Three major renal processes:

19. Renal Filtration Step one of making urine

20. Glomerular Filtration Passive mechanical process driven by hydrostatic pressure The glomerulus is a very efficient filter because – Its filtration membrane is very permeable and it has a large surface area – Glomerular blood pressure is higher (55 mm Hg) than other capillaries Molecules >5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood

21. Figure 25.11 Glomerular capsule Afferent arteriole 10 mm Hg Net filtration pressure Glomerular (blood) hydrostatic pressure (HP g = 55 mm Hg) Blood colloid osmotic pressure (Op g = 30 mm Hg) Capsular hydrostatic pressure (HP c = 15 mm Hg)

22. Glomerular Filtration Rate (GFR) Volume of filtrate formed per minute by the kidneys (120–125 ml/min) Governed by (and directly proportional to) – Total surface area available for filtration – Filtration membrane permeability – NFP

23. Regulation of Glomerular Filtration GFR is tightly controlled by two types of mechanisms Intrinsic controls (renal autoregulation) – Act locally within the kidney Extrinsic controls – Nervous and endocrine mechanisms that maintain blood pressure, but affect kidney function

24. Intrinsic Controls Maintains a nearly constant GFR when MAP is in the range of 80–180 mm Hg Two types of renal autoregulation – Myogenic mechanism (Chapter 19) – Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus

25. Intrinsic Controls: Myogenic Mechanism  BP  constriction of afferent arterioles – Helps maintain normal GFR – Protects glomeruli from damaging high BP  BP  dilation of afferent arterioles – Helps maintain normal GFR

26. Important The next slide is very important for an understanding of GFR

27. Figure 25.12 Stretch of smooth muscle in walls of afferent arterioles Blood pressure in afferent arterioles; GFR Vasodilation of afferent arterioles GFR Myogenic mechanism of autoregulation Release of vasoactive chemical inhibited Intrinsic mechanisms directly regulate GFR despite moderate changes in blood pressure (between 80 and 180 mm Hg mean arterial pressure). Extrinsic mechanisms indirectly regulate GFR by maintaining systemic blood pressure, which drives filtration in the kidneys. Tubuloglomerular mechanism of autoregulation Hormonal (renin-angiotensin) mechanism Neural controls SYSTEMIC BLOOD PRESSURE GFR Macula densa cells of JG apparatus of kidney Filtrate flow and NaCl in ascending limb of Henle’s loop Targets Granular cells of juxtaglomerular apparatus of kidney AngiotensinogenAngiotensin II Adrenal cortexSystemic arterioles (+) Renin Release Catalyzes cascade resulting in conversion (+) Kidney tubules Aldosterone Releases Targets Vasoconstriction; peripheral resistance Blood volume Na + reabsorption; water follows Systemic blood pressure (+) (–) Increase Decrease Stimulates Inhibits Baroreceptors in blood vessels of systemic circulation Sympathetic nervous system (+) (–) Vasodilation of afferent arterioles

28. 5 Effects of Angiotensin!!! 1. Activates smooth muscles of arterioles (vasconstriction) THEREFORE raises BP

29. Angiotensin Effects 2. Stimulates reabsorption of sodium directly – Also indirectly by stimulating ALDOSTERONE – Therefore water follows the Na+ reabsorption – Therefore BV up – Therefore of BP up

30. Angiotensin-5 effects 3. Stimulates hypothalamus To release ADH To activate thirst center

31. Angiostensin Decreases peritubular capillary hydrostatic pressure. How? Afferent arteriole constriction

32. Angiostensin Glomerula mesaglial cells contract Decreases GFR Wht? Since decreases surface area of filtration is decreased.

33. Renal Reabsorption Step 2 in making urine

34. Reabsorption of Nutrients, Water, and Ions Water is reabsorbed by osmosis (obligatory water reabsorption), aided by water-filled pores called aquaporins Cations and fat-soluble substances follow by diffusion

35. Figure 25.14 1 At the basolateral membrane, Na + is pumped into the interstitial space by the Na + -K + ATPase. Active Na + transport creates concentration gradients that drive: 2 “Downhill” Na + entry at the luminal membrane. 4 Reabsorption of water by osmosis. Water reabsorption increases the concentration of the solutes that are left behind. These solutes can then be reabsorbed as they move down their concentration gradients: 3 Reabsorption of organic nutrients and certain ions by cotransport at the luminal membrane. 5 Lipid-soluble substances diffuse by the transcellular route. 6 Cl – (and other anions), K +, and urea diffuse by the paracellular route. Filtrate in tubule lumen Glucose Amino acids Some ions Vitamins Lipid-soluble substances Nucleus Tubule cell Paracellular route Interstitial fluid Peri- tubular capillary Tight junction Primary active transport Passive transport (diffusion) Secondary active transport Transport protein Ion channel or aquaporin Cl –, Ca 2+, K + and other ions, urea Cl – 3Na + 2K + 3Na + 2K + K+K+ H2OH2O Na + 6 5 4 3 2 1

36. Reabsorptive Capabilities of Renal Tubules and Collecting Ducts PCT – Site of most reabsorption 65% of Na + and water All nutrients Ions Small proteins

37. Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Loop of Henle – Descending limb: H 2 O – Ascending limb: Na +, K +, Cl 

38. Reabsorptive Capabilities of Renal Tubules and Collecting Ducts DCT and collecting duct – Reabsorption is hormonally regulated Ca 2+ (PTH) Water (ADH) Na + (aldosterone and ANP)

39. Renal Secretion Step 3 in making urine

40. Tubular Secretion Reabsorption in reverse – K +, H +, NH 4 +, creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrate Disposes of substances that are bound to plasma proteins

41. Tubular Secretion Eliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid) Rids the body of excess K + Controls blood pH by altering amounts of H + or HCO 3 – in urine

42. Formation of Dilute Urine Filtrate is diluted in the ascending loop of Henle In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine Na + and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm

43. Figure 25.17b Active transport Passive transport Small volume of concentrated urine Cortex NaCI Urea H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O Outer medulla Inner medulla (b) Maximal ADH DCT Descending limb of loop of Henle Collecting duct H2OH2O H2OH2O

44. Diuretics Chemicals that enhance the urinary output – Osmotic diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient) – ADH inhibitors such as alcohol – Substances that inhibit Na + reabsorption and obligatory H 2 O reabsorption such as caffeine and many drugs