The Urinary System: Part A

Home , Afferent arterioles, Arcuate vein, Distal convoluted tubule, Efferent arteriole, Glomerulus (kidney), Kidney

10/20/2014

PowerPoint® Lecture Slides Kidney Functions prepared by Barbara Heard, Atlantic Cape Community • Regulating total water volume and total College solute concentration in water • Regulating ECF ion concentrations C H A P T E R 25 • Ensuring long-term acid-base balance • Removal of metabolic wastes, toxins, drugs The Urinary System: Part A

Kidney Functions Urinary System Organs

• Endocrine functions • Kidneys - major excretory organs – Renin - regulation of blood pressure • Ureters - transport urine from kidneys to – Erythropoietin - regulation of RBC urinary bladder production • Urinary bladder - temporary storage • Activation of vitamin D reservoir for urine • Gluconeogenesis during prolonged fasting • Urethra transports urine out of body

Figure 25.1 The urinary system. Figure 25.2b Position of the kidneys against the posterior body wall.

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) 12th rib Urinary bladder

Urethra

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Internal Anatomy Homeostatic Imbalance

• Renal cortex • Pyelitis – Granular-appearing superficial region – Infection of renal pelvis and calyces • Renal medulla • Pyelonephritis – Composed of cone-shaped medullary (renal) – Infection/inflammation of entire kidney pyramids • Normally - successfully treated with – Pyramids separated by renal columns antibiotics • Inward extensions of cortical tissue

Figure 25.2a Position of the kidneys against the posterior body wall. Figure 25.3 Internal anatomy of the kidney.

Renal hilum

Renal cortex

Anterior Inferior Renal medulla vena cava Aorta Peritoneum Peritoneal cavity Major calyx (organs removed) Papilla of Supportive pyramid Renal tissue layers vein Renal pelvis • Renal fascia anterior Minor calyx Renal artery posterior Ureter • Perirenal fat capsule Renal pyramid in renal medulla • Fibrous Body of capsule Renal column vertebra L2 Fibrous capsule Body wall Posterior Photograph of right kidney, frontal section Diagrammatic view

Figure 25.4a Blood vessels of the kidney. Cortical radiate Blood and Nerve Supply vein Cortical radiate artery Arcuate vein • Kidneys cleanse blood; adjust its Arcuate artery composition  rich blood supply Interlobar vein Interlobar artery • Renal arteries deliver ~ ¼ (1200 ml) of Segmental arteries Renal vein cardiac output to kidneys each minute Renal artery • Arterial flow into and venous flow out of Renal pelvis

kidneys follow similar paths Ureter • Nerve supply via sympathetic fibers from renal plexus Renal medulla

Renal cortex

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Figure 25.4b Blood vessels of the kidney. Aorta Inferior vena cava Nephrons

Renal artery Renal vein • Structural and functional units that form Segmental artery Interlobar vein urine

Interlobar artery Arcuate vein • > 1 million per kidney • Two main parts Arcuate artery Cortical radiate vein – Renal corpuscle Peritubular Cortical radiate artery capillaries or vasa recta – Renal tubule

Afferent arteriole Efferent arteriole

Glomerulus (capillaries)

Nephron-associated blood vessels (see Figure 25.7)

Figure 25.5 Location and structure of nephrons. Renal Corpuscle Renal cortex Renal medulla Renal pelvis Glomerular capsule: parietal layer Basement membrane Ureter Podocyte • Two parts of renal corpuscle Kidney Fenestrated endothelium Renal corpuscle of the glomerulus – Glomerulus • Glomerular capsule Glomerular capsule: visceral layer • Glomerulus Distal convoluted Apical Mitochondria • Tuft of capillaries; fenestrated endothelium  tubule microvilli highly porous  allows filtrate formation

Proximal Highly infolded basolateral convoluted – Glomerular capsule (Bowman's capsule) tubule membrane Proximal convoluted tubule cells • Cup-shaped, hollow structure surrounding Cortex Apical side

glomerulus Medulla

Thick Basolateral side Thin segment segment Distal convoluted tubule cells Nephron loop • Descending limb • Ascending limb Nephron loop (thin-segment) cells Collecting duct Principal Intercalated cell cell

Renal Corpuscle Figure 25.5 Location and structure of nephrons. (3 of 7)

• Glomerular capsule Basement – Parietal layer - simple squamous epithelium membrane – Visceral layer - branching epithelial podocytes Podocyte • Extensions terminate in foot processes that cling to basement membrane Fenestrated endothelium • Filtration slits between foot processes allow of the glomerulus filtrate to pass into capsular space Glomerular capsule: visceral layer

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Renal Tubule Renal Tubule

• Three parts • Proximal convoluted tubule (PCT) – Proximal convoluted tubule – Cuboidal cells with dense microvilli (brush • Proximal  closest to renal corpuscle border  surface area); large mitochondria – Nephron loop – Functions in reabsorption and secretion – Distal convoluted tubule – Confined to cortex • Distal  farthest from renal corpuscle

Figure 25.5 Location and structure of nephrons. (4 of 7) Renal Tubule

Apical microvilli Mitochondria • Nephron loop – Descending and ascending limbs – Proximal descending limb continuous with proximal tubule – Distal descending limb = descending thin limb; simple squamous epithelium – Thick ascending limb Highly infolded basolateral membrane • Cuboidal to columnar cells; thin in some nephrons Proximal convoluted tubule cells

Figure 25.5 Location and structure of nephrons. (6 of 7) Renal Tubule

• Distal convoluted tubule (DCT) – Cuboidal cells with very few microvilli – Function more in secretion than reabsorption – Confined to cortex

Nephron loop (thin-segment) cells

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Figure 25.5 Location and structure of nephrons. (5 of 7) Collecting Ducts

• Two cell types Apical side – Principal cells • Sparse, short microvilli • Maintain water and Na+ balance – Intercalated cells • Cuboidal cells; abundant microvilli; two types Basolateral side – A and B; both help maintain acid-base balance of blood Distal convoluted tubule cells

Figure 25.5 Location and structure of nephrons. (7 of 7) Collecting Ducts

• Receive filtrate from many nephrons Principal cell Intercalated cell • Run through medullary pyramids  striped appearance • Fuse together to deliver urine through papillae into minor calyces

Collecting duct cells

Figure 25.5 Location and structure of nephrons. Renal cortex Classes of Nephrons Renal medulla Renal pelvis Glomerular capsule: parietal layer Basement membrane Ureter Podocyte Kidney • Cortical nephrons—85% of nephrons; Fenestrated endothelium Renal corpuscle of the glomerulus • Glomerular capsule Glomerular capsule: visceral layer almost entirely in cortex • Glomerulus Distal convoluted Apical Mitochondria tubule microvilli • Juxtamedullary nephrons – Long nephron loops deeply invade medulla Proximal Highly infolded basolateral convoluted tubule membrane Proximal convoluted tubule cells – Ascending limbs have thick and thin Cortex Apical side segments Medulla

Thick Basolateral side – Important in production of concentrated urine Thin segment segment Distal convoluted tubule cells Nephron loop • Descending limb • Ascending limb Nephron loop (thin-segment) cells Collecting duct Principal Intercalated cell cell

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Figure 25.7a Blood vessels of cortical and juxtamedullary nephrons. Cortical nephron Juxtamedullary nephron • Short nephron loop • Long nephron loop Nephron Capillary Beds • Glomerulus further from the cortex-medulla junction • Glomerulus closer to the cortex-medulla junction • Efferent arteriole supplies peritubular capillaries • Efferent arteriole supplies vasa recta Renal Glomerulus Efferent corpuscle (capillaries) arteriole Cortical radiate vein Glomerular Cortical radiate artery capsule Afferent arteriole Collecting duct Proximal Distal convoluted tubule convoluted • Renal tubules associated with two tubule Afferent Efferent arteriole arteriole capillary beds Peritubular capillaries Ascending limb of – Glomerulus nephron loop

Cortex-medulla junction – Peritubular capillaries Arcuate vein Kidney Arcuate artery Vasa recta Nephron loop Descending • Juxtamedullary nephrons also associated limb of nephron loop with – Vasa recta

Nephron Capillary Beds Nephron Capillary Beds

• Glomerulus - specialized for filtration • Peritubular capillaries • Different from other capillary beds – fed – Low-pressure, porous capillaries adapted for and drained by arteriole absorption of water and solutes – Afferent arteriole  glomerulus  efferent – Arise from efferent arterioles arteriole – Cling to adjacent renal tubules in cortex • Blood pressure in glomerulus high – Empty into venules because – Afferent arterioles larger in diameter than efferent arterioles – Arterioles are high-resistance vessels

Figure 25.7a Blood vessels of cortical and juxtamedullary nephrons. Cortical nephron Juxtamedullary nephron Nephron Capillary Beds • Short nephron loop • Long nephron loop • Glomerulus further from the cortex-medulla junction • Glomerulus closer to the cortex-medulla junction • Efferent arteriole supplies peritubular capillaries • Efferent arteriole supplies vasa recta Renal Glomerulus Efferent corpuscle (capillaries) arteriole Cortical radiate vein Glomerular Cortical radiate artery capsule Afferent arteriole Collecting duct • Vasa recta Proximal Distal convoluted tubule convoluted Afferent tubule arteriole Efferent – Long, thin-walled vessels parallel to long arteriole Peritubular capillaries Ascending nephron loops of juxtamedullary nephrons limb of nephron loop

Cortex-medulla – Arise from efferent arterioles serving junction Arcuate vein Kidney juxtamedullary nephrons Arcuate artery Vasa recta Nephron loop Descending limb of • Instead of peritubular capillaries nephron loop – Function in formation of concentrated urine

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Juxtaglomerular Complex (JGC) Juxtaglomerular Complex (JGC)

• One per nephron • Three cell populations • Involves modified portions of – Macula densa, granular cells, extraglomerular – Distal portion of ascending limb of nephron mesangial cells loop • Macula densa – Afferent (sometimes efferent) arteriole – Tall, closely packed cells of ascending limb • Important in regulation of rate of filtrate – Chemoreceptors; sense NaCl content of formation and blood pressure filtrate

Juxtaglomerular Complex (JGC) Juxtaglomerular Complex (JGC)

• Granular cells (juxtaglomerular, or JG • Extraglomerular mesangial cells cells) – Between arteriole and tubule cells – Enlarged, smooth muscle cells of arteriole – Interconnected with gap junctions – Secretory granules contain enzyme renin – May pass signals between macula densa and – Mechanoreceptors; sense blood pressure in granular cells afferent arteriole

Figure 25.8 Juxtaglomerular complex (JGC) of a nephron. Kidney Physiology: Mechanisms of Urine Formation Glomerular capsule Glomerulus Foot Efferent processes arteriole Parietal layer of podocytes • 180 L fluid processed daily; only 1.5 L  of glomerular Podocyte cell body capsule (visceral layer) Capsular urine Afferent space Red blood cell arteriole Efferent Proximal arteriole tubule cell • Three processes in urine formation and

Juxtaglomerular adjustment of blood composition complex • Macula densa cells – Glomerular filtration of the ascending limb of nephron loop Lumens of • Extraglomerular glomerular – Tubular reabsorption mesangial cells capillaries • Granular Endothelial cell – Tubular secretion cells Afferent of glomerular arteriole capillary Glomerular mesangial cells

Juxtaglomerular complex Renal corpuscle

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Kidney Physiology: Mechanisms of Urine Kidney Physiology: Mechanisms of Urine Formation Formation • Glomerular filtration – produces cell- and • Kidneys filter body's entire plasma volume protein-free filtrate 60 times each day; consume 20-25% oxygen used by body at rest; produce • Tubular reabsorption urine from filtrate – Selectively returns 99% of substances from • Filtrate (produced by glomerular filtration) filtrate to blood in renal tubules and collecting ducts – Blood plasma minus proteins • Urine • Tubular secretion – <1% of original filtrate – Selectively moves substances from blood to – Contains metabolic wastes and unneeded filtrate in renal tubules and collecting ducts substances

Figure 25.9 A schematic, uncoiled nephron showing the three major renal processes that adjust plasma composition. Glomerular Filtration Afferent arteriole Glomerular capillaries

Efferent arteriole Cortical • Passive process radiate artery Glomerular capsule • No metabolic energy required 1

Renal tubule and • Hydrostatic pressure forces fluids and collecting duct containing filtrate solutes through filtration membrane

Peritubular • No reabsorption into capillaries of 2 capillary glomerulus 3 To cortical radiate vein

The Filtration Membrane Figure 25.10a The filtration membrane.

• Porous membrane between blood and Glomerular capsular space Efferent Cytoplasmic extensions interior of glomerular capsule arteriole of podocytes – Water, solutes smaller than plasma proteins Filtration slits pass; normally no cells pass Podocyte Afferent cell body arteriole • Three layers Proximal convoluted – Fenestrated endothelium of glomerular Glomerular tubule capillary covered by Parietal layer Fenestrations podocytes that form of glomerular (pores) capillaries the visceral layer of capsule glomerular capsule – Basement membrane (fused basal laminae Glomerular capillaries and the Glomerular visceral layer of the glomerular capillary endothelium of two other layers) capsule (podocyte covering Foot and basement processes – Foot processes of podocytes with filtration membrane removed) of podocyte slits; slit diaphragms repel macromolecules

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Figure 25.10b The filtration membrane. Figure 25.10c The filtration membrane. Filtration slits Filtration membrane • Capillary endothelium Capillary • Basement membrane

Podocyte • Foot processes of podocyte cell body of glomerular capsule

Foot Filtration processes slit Slit Plasma Filtrate diaphragm in capsular space

Foot Fenestration processes (pore) of podocyte

The Filtration Membrane Pressures That Affect Filtration

• Macromolecules "stuck" in filtration membrane • Outward pressures promote filtrate engulfed by glomerular mesangial cells formation • Allows molecules smaller than 3 nm to pass – Hydrostatic pressure in glomerular – Water, glucose, amino acids, nitrogenous wastes capillaries = Glomerular blood pressure • Plasma proteins remain in blood  maintains • Chief force pushing water, solutes out of blood colloid osmotic pressure  prevents loss of all • Quite high – 55 mm Hg (most capillary beds ~ 26 water to capsular space mm Hg) – Proteins in filtrate indicate membrane problem – Because efferent arteriole is high resistance vessel with diameter smaller than afferent arteriole

Pressures That Affect Filtration Net Filtration Pressure (NFP)

• Inward forces inhibiting filtrate formation • Pressure responsible for filtrate formation

– Hydrostatic pressure in capsular space (HPcs) (10 mm Hg) • Pressure of filtrate in capsule – 15 mm Hg • Main controllable factor determining – Colloid osmotic pressure in capillaries (OPgc) glomerular filtration rate (GFR) • "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

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Figure 25.11 Forces determining net filtration pressure (NFP). Glomerular Glomerular Filtration Rate (GFR) capsule Efferent arteriole • Volume of filtrate formed per minute by both kidneys (normal = 120–125 ml/min) HPgc = 55 mm Hg • GFR directly proportional to OPgc = 30 mm Hg – NFP – primary pressure is hydrostatic pressure in glomerulus Afferent HPcs = 15 mm Hg arteriole – Total surface area available for filtration – glomerular mesangial cells control by contracting NFP = Net filtration pressure – Filtration membrane permeability – much = outward pressures – inward pressures

Regulation of Glomerular Filtration Regulation of Glomerular Filtration

• Constant GFR allows kidneys to make • Intrinsic controls (renal autoregulation) filtrate and maintain extracellular – Act locally within kidney to maintain GFR homeostasis • Extrinsic controls – Goal of intrinsic controls - maintain GFR in kidney – Nervous and endocrine mechanisms that • GFR affects systemic blood pressure maintain blood pressure; can negatively affect kidney function –  GFR  urine output   blood pressure, and vice versa – Take precedence over intrinsic controls if – Goal of extrinsic controls - maintain systemic systemic BP < 80 or > 180 mm Hg blood pressure

Regulation of Glomerular Filtration Intrinsic Controls

• Controlled via glomerular hydrostatic • Maintains nearly constant GFR when MAP pressure in range of 80–180 mm Hg – If rises  NFP rises  GFR rises – Autoregulation ceases if out of that range – If falls only 18% GFR = 0 • Two types of renal autoregulation – Myogenic mechanism – Tubuloglomerular feedback mechanism

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Intrinsic Controls: Myogenic Mechanism Intrinsic Controls: Tubuloglomerular Feedback Mechanism • Smooth muscle contracts when stretched • Flow-dependent mechanism directed by •  BP  muscle stretch  constriction of macula densa cells; respond to filtrate NaCl concentration afferent arterioles  restricts blood flow into glomerulus • If GFR  filtrate flow rate   reabsorption time  high filtrate NaCl – Protects glomeruli from damaging high BP levels  constriction of afferent arteriole •  BP  dilation of afferent arterioles   NFP & GFR  more time for NaCl • Both help maintain normal GFR despite reabsorption normal fluctuations in blood pressure • Opposite for  GFR

Extrinsic Controls: Sympathetic Nervous Extrinsic Controls: Sympathetic Nervous System System • Under normal conditions at rest • If extracellular fluid volume extremely low – Renal blood vessels dilated (blood pressure low) – Renal autoregulation mechanisms prevail – 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

Extrinsic Controls: Renin-Angiotensin- Extrinsic Controls: Other Factors Affecting Aldosterone Mechanism GFR • Main mechanism for increasing blood • Kidneys release chemicals; some act as pressure – see Chapters 16 and 19 paracrines that affect renal arterioles • Three pathways to renin release by – Adenosine granular cells – Prostaglandin E2 – Direct stimulation of granular cells by – Intrinsic angiotensin II – reinforces effects of sympathetic nervous system hormonal angiotensin II – Stimulation by activated macula densa cells when filtrate NaCl concentration low – Reduced stretch of granular cells

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Tubular Reabsorption Tubular Reabsorption

• Most of tubular contents reabsorbed to • Paracellular route blood – Between tubule cells • Selective transepithelial process • Limited by tight junctions, but leaky in proximal – ~ All organic nutrients reabsorbed nephron 2+ 2+ + + – Water and ion reabsorption hormonally – Water, Ca , Mg , K , and some Na in the PCT regulated and adjusted • Includes active and passive tubular reabsorption • Two routes – Transcellular or paracellular

Figure 25.13 Transcellular and paracellular routes of tubular reabsorption. Slide 1 The transcellular route 3 Transport across the The paracellular route Tubular Reabsorption of Sodium involves: basolateral membrane. (Often involves: involves the lateral intercellular • Movement through leaky 1 Transport across the spaces because membrane tight junctions, particularly in apical membrane. transporters transport ions into the PCT. + 2 Diffusion through the these spaces.) • Movement through the inter- • Na - most abundant cation in filtrate cytosol. 4 Movement through the interstitial fluid and into the stitial fluid and into the capillary. capillary. – Transport across basolateral membrane Filtrate Tubule cell Interstitial fluid in tubule Peri- lumen Tight junction Lateral tubular • Primary active transport out of tubule cell by intercellular capillary Na+-K+ ATPase pump  peritubular capillaries space

3 4 – Transport across apical membrane + 1 2 3 4 • Na passes through apical membrane by H2O and solutes Transcellular Capillary secondary active transport or facilitated diffusion route endothelial cell mechanisms Apical membrane

Reabsorption of Nutrients, Water, and Ions Passive Tubular Reabsorption of Water

• Na+ reabsorption by primary active • Movement of Na+ and other solutes transport provides energy and means for creates osmotic gradient for water reabsorbing most other substances • Water reabsorbed by osmosis, aided by • Creates electrical gradient  passive water-filled pores called aquaporins reabsorption of anions – Aquaporins always present in PCT  • Organic nutrients reabsorbed by obligatory water reabsorption secondary active transport; cotransported with Na+ – Aquaporins inserted in collecting ducts only if ADH present  facultative water – Glucose, amino acids, some ions, vitamins reabsorption

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Passive Tubular Reabsorption of Solutes Figure 25.14 Reabsorption by PCT cells. Slide 1

+ 1 At the basolateral membrane, Na+ is 2 “Downhill” Na entry at the pumped into the interstitial space by the apical membrane. Na+-K+ ATPase. Active Na+ transport 3 Reabsorption of organic • Solute concentration in filtrate increases creates concentration gradients that drive: nutrients and certain ions by Filtrate Nucleus Interstitial cotransport at the apical as water reabsorbed  concentration Peri- membrane. in tubule Tubule cell fluid tubular lumen capillary 4 Reabsorption of water by gradients for solutes  osmosis through 2 aquaporins. Water • Fat-soluble substances, some ions and Glucose reabsorption increases the Amino 1 concentration of the acids solutes that are left behind. urea, follow water into peritubular Some 3 ions These solutes can then be Vitamins reabsorbed as they move capillaries down concentration gradients 4 down their gradients: Lipid-soluble substances Lipid- 5 –  Lipid-soluble drugs, environmental soluble 5 diffuse by the transcellular substances route. pollutants difficult to excrete 6 Various − Ions 6 Various ions (e.g., Cl , Tight junction Paracellular Ca2+, K+) and urea diffuse and urea route by the paracellular route. Primary active transport Transport protein Secondary active transport Ion channel Passive transport (diffusion) Aquaporin

Transport Maximum Reabsorptive Capabilities of Renal Tubules and Collecting Ducts • Transcellular transport systems specific • PCT and limited – Site of most reabsorption

– Transport maximum (Tm) for ~ every • All nutrients, e.g., glucose and amino acids reabsorbed substance; reflects number of • 65% of Na+ and water carriers in renal tubules available • Many ions – When carriers saturated, excess excreted in • ~ All uric acid; ½ urea (later secreted back into urine filtrate) • E.g., hyperglycemia  high blood glucose levels

exceed Tm  glucose in urine

Reabsorptive Capabilities of Renal Tubules Reabsorptive Capabilities of Renal Tubules and Collecting Ducts and Collecting Ducts • Nephron loop • DCT and collecting duct

– Descending limb - H2O can leave; solutes – Reabsorption hormonally regulated cannot • Antidiuretic hormone (ADH) – Water • Aldosterone – Na+ (therefore water) – Ascending limb – H2O cannot leave; solutes can • Atrial natriuretic peptide (ANP) – Na+ • Thin segment – passive Na+ movement • PTH – Ca2+ • Thick segment – Na+-K+-2Cl- symporter and Na+- H+ antiporter; some passes by paracellular route

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Reabsorptive Capabilities of Renal Tubules Reabsorptive Capabilities of Renal Tubules and Collecting Ducts and Collecting Ducts • Antidiuretic hormone (ADH) • Aldosterone – Released by posterior pituitary gland – Targets collecting ducts (principal cells) and distal DCT – Causes principal cells of collecting ducts to – Promotes synthesis of apical Na+ and K+ insert aquaporins in apical membranes  channels, and basolateral Na+-K+ ATPases for water reabsorption Na+ reabsorption; water follows • As ADH levels increase  increased water –  little Na+ leaves body; aldosterone absence reabsorption  loss of 2% filtered Na+ daily - incompatible with life – Functions – increase blood pressure; decrease K+ levels

Reabsorptive Capabilities of Renal Tubules Tubular Secretion and Collecting Ducts • Atrial natriuretic peptide • Reabsorption in reverse; almost all in PCT – Reduces blood Na+  decreased blood – Selected substances volume and blood pressure + + + – K , H , NH4 , creatinine, organic acids and – Released by cardiac atrial cells if blood bases move from peritubular capillaries volume or pressure elevated through tubule cells into filtrate • Parathyroid hormone acts on DCT to – Substances synthesized in tubule cells also - increase Ca2+ reabsorption secreted – e.g., HCO3

Tubular Secretion Figure 25.15 Summary of tubular reabsorption and secretion. Cortex

65% of filtrate volume Regulated reabsorption reabsorbed • Na+ (by aldosterone; − • H2O Cl follows) + − 2+ • Na , HCO3 , and • Ca (by parathyroid many other ions hormone) • Glucose, amino acids, • Disposes of substances (e.g., drugs) and other nutrients bound to plasma proteins

+ + • H and NH4 Regulated • Some drugs secretion • Eliminates undesirable substances • K+ (by aldosterone) passively reabsorbed (e.g., urea and uric Outer Regulated medulla reabsorption • H2O (by ADH) acid) • Na+ (by aldosterone; Cl− follows) • Urea (increased • Rids body of excess K+ (aldosterone by ADH) • Urea

effect) Regulated secretion Inner • K+ (by • Controls blood pH by altering amounts of medulla aldosterone)

+ – • Reabsorption or secretion H or HCO in urine to maintain blood pH 3 described in Chapter 26; + − involves H , HCO3 , + and NH4

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Regulation of Urine Concentration and Countercurrent Mechanism Volume • Osmolality of body fluids • Occurs when fluid flows in opposite – Expressed in milliosmols (mOsm) directions in two adjacent segments of – Kidneys maintain osmolality of plasma at same tube with hair pin turn ~300 mOsm by regulating urine concentration – Countercurrent multiplier – interaction of and volume filtrate flow in ascending/descending limbs of – Kidneys regulate with countercurrent nephron loops of juxtamedullary nephrons mechanism – Countercurrent exchanger - Blood flow in ascending/descending limbs of vasa recta

Figure 25.16a Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. (1 of 4) The Countercurrent Multiplier

The three key players and their • Constant 200 mOsm difference between orientation in the osmotic gradient:

(c) The collecting ducts of two limbs of nephron loop and between all nephrons use the gradient to adjust urine osmolality. ascending limb and interstitial fluid 300

300 • Difference "multiplied" along length of loop

400 to ~ 900 mOsm (a) The long nephron loops of juxtamedullary nephrons create the gradient. They act as 600 countercurrent multipliers. The osmolality of the medullary 900 interstitial fluid progressively increases from the 300 mOsm of (b) The vasa recta preserve the normal body fluid to 1200 mOsm gradient. They act as at the deepest part of the medulla. countercurrent exchangers. 1200

Figure 25.16a Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to The Countercurrent Exchanger produce urine of varying concentration. (4 of 4)

(continued) As water and solutes are reabsorbed, the loop first concentrates the filtrate, then dilutes it. • Vasa recta Active transport Passive transport Water impermeable 300 • Preserve medullary gradient 300 100 Cortex 100 300 300 1 Filtrate entering the 5 Filtrate is at its most dilute as it – Prevent rapid removal of salt from interstitial nephron loop is isosmotic to leaves the nephron loop. At both blood plasma and 100 mOsm, it is hypo-osmotic space cortical interstitial fluid. to the interstitial fluid. – Remove reabsorbed water 400 400 200 4 Na+ and Cl- are pumped out Outer of the filtrate. This increases the medulla interstitial fluid osmolality. • Water entering ascending vasa recta 600 600 400 2 Water moves out of the either from descending vasa recta or filtrate in the descending limb down its osmotic gradient. This concentrates the filtrate.

reabsorbed from nephron loop and 900 900 700 Osmolality Osmolality of interstitial fluid (mOsm) 3 Filtrate reaches its highest collecting duct  concentration at the bend of the Inner loop. medulla Nephron loop – Volume of blood at end of vasa recta greater 1200 1200 than at beginning

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Figure 25.16b Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to Figure 25.16c Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. produce urine of varying concentration.

Vasa recta preserve the gradient. Collecting ducts use the gradient.

The entire length of the vasa recta is highly permeable to water Under the control of antidiuretic hormone, the collecting and solutes. Due to countercurrent exchanges between each ducts determine the final concentration and volume of section of the vasa recta and its surrounding interstitial fluid, the urine. This process is fully described in Figure 25.17. blood within the vasa recta remains nearly isosmotic to the surrounding fluid. As a result, the vasa recta do not undo the osmotic gradient as they remove reabsorbed water and solutes. Collecting duct Blood from efferent To vein arteriole 300

300 325

300 400 400 The countercurrent flow of fluid moves 400 through two adjacent parallel sections of the vasa recta.

600 600

600

900 900 Osmolality Osmolality ofinterstitial fluid(mOsm)

900

Figure 25.17 Mechanism for forming dilute or concentrated urine. Formation of Dilute or Concentrated Urine If we were so overhydrated we had no ADH... If we were so dehydrated we had maximal ADH...

Osmolality of extracellular fluids Osmolality of extracellular fluids

ADH release from posterior pituitary ADH release from posterior pituitary

Number of aquaporins (H2O channels) in collecting duct Number of aquaporins (H2O channels) in collecting duct • Osmotic gradient used to raise urine H2O reabsorption from collecting duct H2O reabsorption from collecting duct concentration > 300 mOsm to conserve Large volume of dilute urine Small volume of concentrated urine Collecting Collecting duct duct water Descending limb 300 Descending limb 300 of nephron loop of nephron loop 100 100 150

– Overhydration  large volume dilute urine DCT 100 DCT 300 Cortex Cortex • ADH production ; urine ~ 100 mOsm 300 100 300 300 100 300 300

• If aldosterone present, additional ions removed  400

~ 50 mOsm 600 400 600 600 400 600 600 100 Outer Outer – Dehydration  small volume concentrated medulla medulla Urea

urine 900 700 900 900 700 900 900

Osmolality interstitial (mOsm) Osmolality fluid of Osmolality interstitial (mOsm) Osmolality fluid of • Maximal ADH released; urine ~ 1200 mOsm Urea Urea Inner Inner medulla medulla 100 • Severe dehydration – 99% water reabsorbed 1200 1200 1200 1200 1200 Large volume Small volume of of dilute urine Urea contributes to concentrated urine Active transport the osmotic gradient. Passive transport ADH increases its recycling.

Urea Recycling and the Medullary Osmotic Diuretics Gradient • Urea helps form medullary gradient • Chemicals that enhance urinary output – Enters filtrate in ascending thin limb of – ADH inhibitors, e.g., alcohol nephron loop by facilitated diffusion + – Na reabsorption inhibitors (and resultant H2O – Cortical collecting duct reabsorbs water; reabsorption), e.g., caffeine, drugs for leaves urea hypertension or edema – In deep medullary region now highly – Loop diuretics inhibit medullary gradient concentrated urea  interstitial fluid of formation medulla  back to ascending thin limb  – Osmotic diuretics - substance not reabsorbed high osmolality in medulla so water remains in urine, e.g., high glucose of diabetic patient

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Renal Clearance Renal Clearance

• Volume of plasma kidneys clear of • C = UV/P particular substance in given time – C = renal clearance rate (ml/min) • Renal clearance tests used to determine – U = concentration (mg/ml) of substance in GFR urine – To detect glomerular damage – V = flow rate of urine formation (ml/min) – To follow progress of renal disease – P = concentration of same substance in plasma

Renal Clearance Homeostatic Imbalance

• Inulin (plant polysaccharide) is standard used • Chronic renal disease - GFR < 60 ml/min – Freely filtered; neither reabsorbed nor secreted by for 3 months kidneys; its renal clearance = GFR = 125 ml/min – E.g., in diabetes mellitus; hypertension • If C < 125 ml/min, substance reabsorbed • Renal failure – GFR < 15 ml/min • If C = 0, substance completely reabsorbed, or not filtered – Causes uremia – ionic and hormonal imbalances; metabolic abnormalities; toxic • If C = 125 ml/min, no net reabsorption or molecule accumulation secretion – Treated with hemodialysis or transplant • If C > 125 ml/min, substance secreted (most drug metabolites)

Physical Characteristics of Urine Physical Characteristics of Urine

• Color and transparency • Odor – Clear – Slightly aromatic when fresh • Cloudy may indicate urinary tract infection – Develops ammonia odor upon standing – Pale to deep yellow from urochrome • As bacteria metabolize solutes • Pigment from hemoglobin breakdown; more – May be altered by some drugs and concentrated urine  deeper color vegetables – Abnormal color (pink, brown, smoky) • Food ingestion, bile pigments, blood, drugs

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Physical Characteristics of Urine Chemical Composition of Urine

• pH • 95% water and 5% solutes – Slightly acidic (~pH 6, with range of 4.5 to 8.0) • Nitrogenous wastes • Acidic diet (protein, whole wheat)   pH – Urea (from amino acid breakdown) – largest • Alkaline diet (vegetarian), prolonged vomiting, or solute component urinary tract infections  pH – Uric acid (from nucleic acid metabolism) • Specific gravity – Creatinine (metabolite of creatine phosphate) – 1.001 to 1.035; dependent on solute concentration

Chemical Composition of Urine Urine transport, Storage, and Elimination: Ureters • Other normal solutes • Convey urine from kidneys to bladder + + 3– 2– 2+ 2+ – Na , K , PO4 , and SO4 , Ca , Mg and – Begin at L2 as continuation of renal pelvis – HCO3 • Retroperitoneal • Abnormally high concentrations of any • Enter base of bladder through posterior constituent, or abnormal components, e.g., wall blood proteins, WBCs, bile pigments, may – As bladder pressure increases, distal ends of indicate pathology ureters close, preventing backflow of urine

Homeostatic Imbalance Urinary Bladder

• Renal calculi - kidney stones in renal • Muscular sac for temporary storage of pelvis urine – Crystallized calcium, magnesium, or uric acid salts • Retroperitoneal, on pelvic floor posterior to pubic symphysis • Large stones block ureter  pressure & pain – Males—prostate inferior to bladder neck • May be due to chronic bacterial infection, – Females—anterior to vagina and uterus urine retention, Ca2+ in blood, pH of urine • Treatment - shock wave lithotripsy – noninvasive; shock waves shatter calculi

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Urinary Bladder Urinary Bladder

• Openings for ureters and urethra • Layers of bladder wall • Trigone – Mucosa - transitional epithelial mucosa – Smooth triangular area outlined by openings – Thick detrusor - three layers of smooth for ureters and urethra muscle – Infections tend to persist in this region – Fibrous adventitia (peritoneum on superior surface only)

Urinary Bladder Figure 25.18 Pyelogram.

• Collapses when empty; rugae appear Kidney Renal • Expands and rises superiorly during filling pelvis without significant rise in internal pressure • ~ Full bladder 12 cm long; holds ~ 500 ml Ureter – Can hold ~ twice that if necessary – Can burst if overdistended

Urinary bladder

Figure 25.20a Structure of the urinary bladder and urethra. Figure 25.20b Structure of the urinary bladder and urethra. Peritoneum Peritoneum Ureter Rugae Ureter Detrusor Adventitia Ureteric orifices Rugae Trigone of bladder Detrusor Bladder neck Internal urethral sphincter Prostate Ureteric orifices Prostatic urethra Intermediate part of the urethra External urethral sphincter Bladder neck Urogenital diaphragm Internal urethral sphincter

Trigone Spongy urethra Erectile tissue of penis External urethral sphincter Urogenital diaphragm Urethra External urethral orifice External urethral orifice Male. The long male urethra has three regions: prostatic, intermediate, and spongy. Female. © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc.

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Urethra Urethra

• Sphincters • Female urethra (3–4 cm) – Internal urethral sphincter – Tightly bound to anterior vaginal wall • Involuntary (smooth muscle) at bladder-urethra – External urethral orifice junction • Anterior to vaginal opening; posterior to clitoris • Contracts to open – External urethral sphincter • Voluntary (skeletal) muscle surrounding urethra as it passes through pelvic floor

Figure 25.20a Structure of the urinary bladder and urethra. Urethra Peritoneum Ureter Rugae Detrusor Adventitia • Male urethra carries semen and urine Ureteric orifices Trigone of bladder Bladder neck – Three named regions Internal urethral sphincter Prostate • Prostatic urethra (2.5 cm)—within prostate Prostatic urethra • Intermediate part of the urethra (membranous Intermediate part of the urethra External urethral sphincter urethra) (2 cm)—passes through urogenital Urogenital diaphragm diaphragm from prostate to beginning of penis • Spongy urethra (15 cm)—passes through penis; opens via external urethral orifice Spongy urethra Erectile tissue of penis

Micturition Micturition

• Urination or voiding • Reflexive urination (urination in infants) • Three simultaneous events must occur – Distension of bladder activates stretch – Contraction of detrusor by ANS receptors – Opening of internal urethral sphincter by ANS – Excitation of parasympathetic neurons in reflex center in sacral region of spinal cord – Opening of external urethral sphincter by somatic nervous system – Contraction of detrusor – Contraction (opening) of internal sphincter – Inhibition of somatic pathways to external sphincter, allowing its relaxation (opening)

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Figure 25.21 Control of micturition. Homeostatic Imbalance

Brain Higher brain Urinary bladder centers fills, stretching bladder wall Allow or inhibit micturition as appropriate • Incontinence usually from weakened

Afferent impulses Pontine micturition Pontine storage pelvic muscles from stretch center center receptors – Stress incontinence Simple Promotes micturition Inhibits micturition by spinal by acting on all three acting on all three reflex spinal efferents Spinal efferents • Increased intra-abdominal pressure forces urine

Spinal Spinal through external sphincter cord cord

Parasympathetic Sympathetic Somatic motor Parasympathetic activity – Overflow incontinence activity activity nerve activity Sympathetic activity Somatic motor nerve activity • Urine dribbles when bladder overfills

Detrusor contracts; External urethral internal urethral sphincter opens sphincter opens

Inhibits Micturition

Homeostatic Imbalance Developmental Aspects

• Urinary retention • Three sets of embryonic kidneys form in – Bladder unable to expel urine succession – Common after general anesthesia – Pronephros degenerates but pronephric – Hypertrophy of prostate duct persists – Treatment - catheterization – Mesonephros claims this duct; becomes mesonephric duct – Metanephros develop by fifth week, develops into adult kidneys and ascends

Figure 25.22a Development of the urinary system in the embryo. Figure 25.22b Development of the urinary system in the embryo. Degenerating pronephros

Degenerating pronephros Developing digestive tract

Urogenital Duct to ridge yolk sac Duct to yolk sac Allantois Mesonephros Allantois Body stalk

Cloaca Urogenital sinus Mesonephric duct Ureteric bud Rectum (initially, pronephric duct) Mesonephros Ureteric bud Hindgut Mesonephric Week 5 duct Metanephros Week 6

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Developmental Aspects Figure 25.22c Development of the urinary system in the embryo.

• Metanephros develops as ureteric buds that induce mesoderm of urogenital ridge Urogenital to form nephrons sinus – Distal ends of ureteric buds form renal pelves, Gonad (developing calyces, and collecting ducts urinary bladder) – Proximal ends become ureters Rectum • Kidneys excrete urine into amniotic fluid by Metanephros third month (kidney) • Cloaca subdivides into rectum, anal canal, and urogenital sinus Week 7

Figure 25.22d Development of the urinary system in the embryo. Homeostatic Imbalance

• Three common congenital abnormalities • Horseshoe kidney – Two kidneys fuse across midline  single U- Urinary bladder Gonad shaped kidney; usually asymptomatic Urethra Kidney • Hypospadias Anus – Urethral orifice on ventral surface of penis

Ureter Rectum – Corrected surgically at ~ 12 months

Week 8

Homeostatic Imbalance Developmental Aspects

• Polycystic kidney disease • Frequent micturition in infants due to small bladders and less-concentrated urine – Many fluid-filled cysts interfere with function • Incontinence normal in infants: control of • Autosomal dominant form – less severe but more voluntary urethral sphincter develops with common nervous system • Autosomal recessive – more severe • E. coli bacteria account for 80% of all urinary – Cause unknown but involves defect in tract infections signaling proteins • Untreated childhood streptococcal infections may cause long-term renal damage • Sexually transmitted diseases can also inflame urinary tract

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Developmental Aspects

• Most elderly people have abnormal kidneys histologically – Kidneys shrink; nephrons decrease in size and number; tubule cells less efficient – GFR ½ that of young adult by age 80 • Possibly from atherosclerosis of renal arteries • Bladder shrinks; loss of bladder tone  nocturia and incontinence