Regulating total water volume and total solute concentration in water Kidney Functions Regulating total water volume and total solute concentration in water Regulating ECF ion concentrations Ensuring long-term acid-base balance Removal of metabolic wastes, toxins, drugs © 2013 Pearson Education, Inc.

Activation of vitamin D Kidney Functions Endocrine functions Renin - regulation of blood pressure Erythropoietin - regulation of RBC production Activation of vitamin D © 2013 Pearson Education, Inc.

Kidneys - major excretory organs Urinary System Organs Kidneys - major excretory organs Ureters - transport urine from kidneys to urinary bladder Urinary bladder - temporary storage reservoir for urine Urethra transports urine out of body © 2013 Pearson Education, Inc.

Figure 25.1 The urinary system. Hepatic veins (cut) Esophagus (cut) Inferior vena cava Renal artery Adrenal gland Renal hilum Aorta Renal vein Kidney Iliac crest Ureter Rectum (cut) Uterus (part of female reproductive system) Urinary bladder Urethra © 2013 Pearson Education, Inc.

Internal Anatomy Renal cortex Renal medulla Granular-appearing superficial region Renal medulla Composed of cone-shaped medullary (renal) pyramids © 2013 Pearson Education, Inc.

Figure 25.4a Blood vessels of the kidney. Cortical radiate vein Cortical radiate artery Arcuate vein Arcuate artery Interlobar vein Interlobar artery Segmental arteries Renal vein Renal artery Renal pelvis Ureter Renal medulla Renal cortex Frontal section illustrating major blood vessels © 2013 Pearson Education, Inc.

Structural and functional units that form urine Nephrons Structural and functional units that form urine > 1 million per kidney Two main parts Renal corpuscle Renal tubule © 2013 Pearson Education, Inc.

Two parts of renal corpuscle Glomerulus Tuft of capillaries; fenestrated endothelium  highly porous  allows filtrate formation Glomerular capsule (Bowman's capsule) Cup-shaped, hollow structure surrounding glomerulus © 2013 Pearson Education, Inc.

Figure 25.5 Location and structure of nephrons. Renal cortex Renal medulla Renal pelvis Glomerular capsule: parietal layer Basement membrane Ureter Podocyte Kidney Fenestrated endothelium of the glomerulus Renal corpuscle • Glomerular capsule Glomerular capsule: visceral layer • Glomerulus Distal convoluted tubule Apical microvilli Mitochondria Highly infolded basolateral membrane Proximal convoluted tubule Proximal convoluted tubule cells Cortex Apical side Medulla Basolateral side Thick segment Thin segment Distal convoluted tubule cells Nephron loop • Descending limb • Ascending limb Nephron loop (thin-segment) cells Collecting duct Principal cell Intercalated cell Collecting duct cells © 2013 Pearson Education, Inc.

Renal Tubule Three parts Proximal convoluted tubule Nephron loop Proximal  closest to renal corpuscle Nephron loop Distal convoluted tubule Distal  farthest from renal corpuscle -> Collecting duct © 2013 Pearson Education, Inc.

Proximal convoluted tubule (PCT) Renal Tubule Proximal convoluted tubule (PCT) Cuboidal cells with dense microvilli (brush border  surface area); large mitochondria Functions in reabsorption and secretion Confined to cortex © 2013 Pearson Education, Inc.

Renal Tubule Nephron loop Descending and ascending limbs Distal descending limb = descending thin limb; simple squamous epithelium Thick ascending limb Cuboidal to columnar cells; thin in some nephrons © 2013 Pearson Education, Inc.

Distal convoluted tubule (DCT) Renal Tubule Distal convoluted tubule (DCT) Cuboidal cells with very few microvilli Function more in secretion than reabsorption Confined to cortex © 2013 Pearson Education, Inc.

Receive filtrate from many nephrons Two cell types Collecting Ducts Receive filtrate from many nephrons Two cell types Principal cells Sparse, short microvilli Maintain water and Na+ balance Intercalated cells Cuboidal cells; abundant microvilli; two types A and B; both help maintain acid-base balance of blood © 2013 Pearson Education, Inc.

Cortical nephrons—85% of nephrons; almost entirely in cortex Classes of Nephrons Cortical nephrons—85% of nephrons; almost entirely in cortex Juxtamedullary nephrons Long nephron loops deeply invade medulla Important in production of concentrated urine © 2013 Pearson Education, Inc.

Figure 25.7a Blood vessels of cortical and juxtamedullary nephrons. Cortical nephron Juxtamedullary nephron • Short nephron loop • Glomerulus further from the cortex-medulla junction • Efferent arteriole supplies peritubular capillaries • Long nephron loop • Glomerulus closer to the cortex-medulla junction • Efferent arteriole supplies vasa recta Renal corpuscle Glomerulus (capillaries) Efferent arteriole Cortical radiate vein Cortical radiate artery Glomerular capsule Afferent arteriole Collecting duct Proximal convoluted tubule Distal convoluted tubule Afferent arteriole Efferent arteriole Peritubular capillaries Ascending limb of nephron loop Cortex-medulla junction Arcuate vein Kidney Arcuate artery Vasa recta Nephron loop Descending limb of nephron loop © 2013 Pearson Education, Inc.

Nephron Capillary Beds Renal tubule associated with two capillary beds Glomerulus Peritubular capillaries Juxtamedullary nephron associated with Vasa recta Important in regulation of rate of filtrate formation and blood pressure © 2013 Pearson Education, Inc.

Nephron Capillary Beds Glomerulus - specialized for filtration Different from other capillary beds – fed and drained by arteriole Afferent arteriole  glomerulus  efferent arteriole Blood pressure in glomerulus high because Afferent arterioles larger in diameter than efferent arterioles Arterioles are high-resistance vessels © 2013 Pearson Education, Inc.

Nephron Capillary Beds Peritubular capillaries Low-pressure, porous capillaries adapted for absorption of water and solutes Arise from efferent arterioles Cling to adjacent renal tubules in cortex Empty into venules © 2013 Pearson Education, Inc.

Juxtaglomerular Complex (JGC) Two important cell type: Macula densa, granular cells, Macula densa: Tall, closely packed cells of ascending limb Chemoreceptors; sense NaCl content of filtrate Granular cells (juxtaglomerular, or JG cells) Enlarged, smooth muscle cells of arteriole Secretory granules contain enzyme renin Mechanoreceptors; sense blood pressure in afferent arteriole © 2013 Pearson Education, Inc.

Juxtaglomerular Complex (JGC) Granular cells (juxtaglomerular, or JG cells) Enlarged, smooth muscle cells of arteriole Secretory granules contain enzyme renin Mechanoreceptors; sense blood pressure in afferent arteriole © 2013 Pearson Education, Inc.

Figure 25.8 Juxtaglomerular complex (JGC) of a nephron. capsule Glomerulus Foot processes of podocytes Efferent arteriole Parietal layer of glomerular capsule Podocyte cell body (visceral layer) Capsular space Afferent arteriole Red blood cell Efferent arteriole Proximal tubule cell Juxtaglomerular complex • Macula densa cells of the ascending limb of nephron loop Lumens of glomerular capillaries • Extraglomerular mesangial cells • Granular cells Endothelial cell of glomerular capillary Afferent arteriole Glomerular mesangial cells Juxtaglomerular complex Renal corpuscle © 2013 Pearson Education, Inc.

Kidney Physiology: Mechanisms of Urine Formation Three processes in urine formation and adjustment of blood composition Glomerular filtration Tubular reabsorption Tubular secretion © 2013 Pearson Education, Inc.

Kidney Physiology: Mechanisms of Urine Formation Glomerular filtration – produces cell- and protein-free filtrate Tubular reabsorption Selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts Tubular secretion Selectively moves substances from blood to filtrate in renal tubules and collecting ducts © 2013 Pearson Education, Inc.

Kidney Physiology: Mechanisms of Urine Formation Filtrate (produced by glomerular filtration) Blood plasma minus proteins Urine <1% of original filtrate Contains metabolic wastes and unneeded substances © 2013 Pearson Education, Inc.

To cortical radiate vein Glomerular filtration Figure 25.9 A schematic, uncoiled nephron showing the three major renal processes that adjust plasma composition. Afferent arteriole Glomerular capillaries Efferent arteriole Cortical radiate artery Glomerular capsule 1 Renal tubule and collecting duct containing filtrate Peritubular capillary 2 3 To cortical radiate vein Three major renal processes: Urine 1 Glomerular filtration 2 Tubular reabsorption 3 Tubular secretion © 2013 Pearson Education, Inc.

Glomerular Filtration Passive process No metabolic energy required Hydrostatic pressure forces fluids and solutes through filtration membrane No reabsorption into capillaries of glomerulus © 2013 Pearson Education, Inc.

The Filtration Membrane Porous membrane between blood and interior of glomerular capsule Water, solutes smaller than plasma proteins pass; normally no cells pass Three layers Fenestrated endothelium of glomerular capillaries Basement membrane (fused basal laminae of two other layers) Foot processes of podocytes with filtration slits; slit diaphragms repel macromolecules © 2013 Pearson Education, Inc.

Figure 25.10a The filtration membrane. Glomerular capsular space Efferent arteriole Cytoplasmic extensions of podocytes Filtration slits Podocyte cell body Afferent arteriole Proximal convoluted tubule Glomerular capillary covered by podocytes that form the visceral layer of glomerular capsule Parietal layer of glomerular capsule Fenestrations (pores) Glomerular capillaries and the visceral layer of the glomerular capsule Glomerular capillary endothelium (podocyte covering and basement membrane removed) Foot processes of podocyte © 2013 Pearson Education, Inc.

Figure 25.10c The filtration membrane. • Capillary endothelium Capillary • Basement membrane • Foot processes of podocyte of glomerular capsule Filtration slit Slit diaphragm Plasma Filtrate in capsular space Foot processes of podocyte Fenestration (pore) Three layers of the filtration membrane © 2013 Pearson Education, Inc.

The Filtration Membrane Macromolecules "stuck" in filtration membrane Allows molecules smaller than 3 nm to pass Water, glucose, amino acids, nitrogenous wastes Plasma proteins remain in blood  maintains colloid osmotic pressure  prevents loss of all water to capsular space Proteins in filtrate indicate membrane problem © 2013 Pearson Education, Inc.

Pressures That Affect Filtration Outward pressures promote filtrate formation Hydrostatic pressure in glomerular capillaries = Glomerular blood pressure Chief force pushing water, solutes out of blood Quite high – 55 mm Hg (most capillary beds ~ 26 mm Hg) Because efferent arteriole is high resistance vessel with diameter smaller than afferent arteriole © 2013 Pearson Education, Inc.

Pressures That Affect Filtration Inward forces inhibiting filtrate formation Hydrostatic pressure in capsular space (HPcs) Pressure of filtrate in capsule – 15 mm Hg Colloid osmotic pressure in capillaries (OPgc) "Pull" of proteins in blood – 30 mm Hg Sum of forces  Net filtration pressure (NFP) 55 mm Hg forcing out; 45 mm Hg opposing = net outward force of 10 mm Hg © 2013 Pearson Education, Inc.

Net Filtration Pressure (NFP) Pressure responsible for filtrate formation (10 mm Hg) Main controllable factor determining glomerular filtration rate (GFR) © 2013 Pearson Education, Inc.

Figure 25.11 Forces determining net filtration pressure (NFP). Glomerular capsule Efferent arteriole HPgc = 55 mm Hg OPgc = 30 mm Hg Afferent arteriole HPcs = 15 mm Hg NFP = Net filtration pressure = outward pressures – inward pressures = (HPgc) – (HPcs + OPgc) = (55) – (15 + 30) = 10 mm Hg © 2013 Pearson Education, Inc.

Regulation of Glomerular Filtration Volume of filtrate formed per minute by both kidneys (normal = 120–125 ml/min) Constant GFR allows kidneys to make filtrate and maintain extracellular homeostasis Goal of intrinsic controls - maintain GFR in kidney GFR affects systemic blood pressure  GFR  urine output   blood pressure, and vice versa Goal of extrinsic controls - maintain systemic blood pressure © 2013 Pearson Education, Inc.

Regulation of Glomerular Filtration Intrinsic controls (renal autoregulation) Act locally within kidney to maintain GFR Extrinsic controls Nervous and endocrine mechanisms that maintain blood pressure; can negatively affect kidney function © 2013 Pearson Education, Inc.

Two types of renal autoregulation Intrinsic Controls Two types of renal autoregulation Myogenic mechanism Tubuloglomerular feedback mechanism © 2013 Pearson Education, Inc.

Intrinsic Controls: Myogenic Mechanism Smooth muscle contracts when stretched  BP  muscle stretch  constriction of afferent arterioles  restricts blood flow into glomerulus Protects glomeruli from damaging high BP  BP  dilation of afferent arterioles Both help maintain normal GFR despite normal fluctuations in blood pressure © 2013 Pearson Education, Inc.

Intrinsic Controls: Tubuloglomerular Feedback Mechanism Flow-dependent mechanism directed by macula densa cells; respond to filtrate NaCl concentration If GFR  filtrate flow rate   reabsorption time  high filtrate NaCl levels  constriction of afferent arteriole   NFP & GFR  more time for NaCl reabsorption Opposite for  GFR © 2013 Pearson Education, Inc.

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 © 2013 Pearson Education, Inc.

Effects of Angiotensin II Constricts arteriolar smooth muscle, causing MAP to rise Stimulates the reabsorption of Na+ Acts directly on the renal tubules Triggers adrenal cortex to release aldosterone Stimulates the hypothalamus to release ADH and activates the thirst center © 2013 Pearson Education, Inc.

Effects of Angiotensin II Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration © 2013 Pearson Education, Inc.

Extrinsic Controls: Renin-Angiotensin Mechanism Triggers for renin release by granular cells Reduced stretch of granular cells (MAP below 80 mm Hg) Stimulation of the granular cells by activated macula densa cells Direct stimulation of granular cells via 1-adrenergic receptors by renal nerves © 2013 Pearson Education, Inc.

afferent arterioles; GFR peripheral resistance SYSTEMIC BLOOD PRESSURE (–) Blood pressure in afferent arterioles; GFR GFR Granular cells of juxtaglomerular apparatus of kidney Baroreceptors in blood vessels of systemic circulation Release Stretch of smooth muscle in walls of afferent arterioles Filtrate flow and NaCl in ascending limb of Henle’s loop (+) (+) Renin (+) Sympathetic nervous system Catalyzes cascade resulting in conversion Targets Vasodilation of afferent arterioles Angiotensinogen Angiotensin II (+) (+) Macula densa cells of JG apparatus of kidney (+) Adrenal cortex Systemic arterioles Releases Aldosterone Vasoconstriction; peripheral resistance Release of vasoactive chemical inhibited Targets Kidney tubules Vasodilation of afferent arterioles Na+ reabsorption; water follows (+) Stimulates (–) Inhibits Increase Decrease GFR Blood volume Systemic blood pressure Myogenic mechanism of autoregulation Tubuloglomerular mechanism of autoregulation Hormonal (renin-angiotensin) mechanism Neural controls 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. © 2013 Pearson Education, Inc. Figure 25.12

Extrinsic Controls: Sympathetic Nervous System Under normal conditions at rest Renal blood vessels dilated Renal autoregulation mechanisms prevail © 2013 Pearson Education, Inc.

Extrinsic Controls: Sympathetic Nervous System If extracellular fluid volume extremely low (blood pressure low) Norepinephrine released by sympathetic nervous system; epinephrine released by adrenal medulla  Systemic vasoconstriction  increased blood pressure Constriction of afferent arterioles   GFR  increased blood volume and pressure © 2013 Pearson Education, Inc.