25 The Urinary System.

25 The Urinary System

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 Gluconeogenesis during prolonged fasting
Kidney Functions Endocrine functions Renin - regulation of blood pressure Erythropoietin - regulation of RBC production Activation of vitamin D Gluconeogenesis during prolonged fasting © 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.

Retroperitoneal, in the superior lumbar region; ~ T12 to L5
Kidney Anatomy Retroperitoneal, in the superior lumbar region; ~ T12 to L5 Right kidney crowded by liver  lower than left Adrenal (suprarenal) gland atop each kidney Convex lateral surface, concave medial surface; vertical renal hilum leads to renal sinus Ureters, renal blood vessels, lymphatics, and nerves enter and exit at hilum © 2013 Pearson Education, Inc.

Figure 25.2b Position of the kidneys against the posterior body wall.
12th rib © 2013 Pearson Education, Inc.

Layers of surrounding supportive tissue
Kidney Anatomy Layers of surrounding supportive tissue Renal fascia Anchoring outer layer of dense fibrous connective tissue Perirenal fat capsule Fatty cushion Fibrous capsule Prevents spread of infection to kidney © 2013 Pearson Education, Inc.

Internal Anatomy Renal cortex Renal medulla
Granular-appearing superficial region Renal medulla Composed of cone-shaped medullary (renal) pyramids Pyramids separated by renal columns Inward extensions of cortical tissue © 2013 Pearson Education, Inc.

Internal Anatomy Papilla Lobe Renal pelvis
Tip of pyramid; releases urine into minor calyx Lobe Medullary pyramid and its surrounding cortical tissue; ~ 8/kidney Renal pelvis Funnel-shaped tube continuous with ureter © 2013 Pearson Education, Inc.

Internal Anatomy Minor calyces Major calyces Urine flow
Drain pyramids at papillae Major calyces Collect urine from minor calyces Empty urine into renal pelvis Urine flow Renal pyramid  minor calyx  major calyx  renal pelvis  ureter © 2013 Pearson Education, Inc.

Homeostatic Imbalance
Pyelitis Infection of renal pelvis and calyces Pyelonephritis Infection/inflammation of entire kidney Normally - successfully treated with antibiotics © 2013 Pearson Education, Inc.

Figure 25.2a Position of the kidneys against the posterior body wall.
Anterior Inferior vena cava Aorta Peritoneum Peritoneal cavity (organs removed) Supportive tissue layers Renal vein • Renal fascia anterior posterior Renal artery • Perirenal fat capsule • Fibrous capsule Body of vertebra L2 Body wall Posterior © 2013 Pearson Education, Inc.

Figure 25.3 Internal anatomy of the kidney.
Renal hilum Renal cortex Renal medulla Major calyx Papilla of pyramid Renal pelvis Minor calyx Ureter Renal pyramid in renal medulla Renal column Fibrous capsule Photograph of right kidney, frontal section Diagrammatic view © 2013 Pearson Education, Inc.

Kidneys cleanse blood; adjust its composition  rich blood supply
Blood and Nerve Supply Kidneys cleanse blood; adjust its composition  rich blood supply Renal arteries deliver ~ ¼ (1200 ml) of cardiac output to kidneys each minute Arterial flow into and venous flow out of kidneys follow similar paths Nerve supply via sympathetic fibers from renal plexus © 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.

Figure 25.4b Blood vessels of the kidney.
Aorta Inferior vena cava Renal artery Renal vein Segmental artery Interlobar vein Interlobar artery Arcuate vein Arcuate artery Cortical radiate vein Peritubular capillaries or vasa recta Cortical radiate artery Afferent arteriole Efferent arteriole Glomerulus (capillaries) Nephron-associated blood vessels (see Figure 25.7) (b) Path of blood flow through renal 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 Corpuscle Glomerular capsule
Parietal layer - simple squamous epithelium Visceral layer - branching epithelial podocytes Extensions terminate in foot processes that cling to basement membrane Filtration slits between foot processes allow filtrate to pass into capsular space © 2013 Pearson Education, Inc.

Figure 25.5 Location and structure of nephrons. (2 of 7)
Glomerular capsule: parietal layer © 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 © 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
Proximal descending limb continuous with proximal tubule 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.

Collecting Ducts Two cell types Principal cells Intercalated 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.

Receive filtrate from many nephrons
Collecting Ducts Receive filtrate from many nephrons Run through medullary pyramids  striped appearance Fuse together to deliver urine through papillae into minor calyces © 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.

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 Ascending limbs have thick and thin segments 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 tubules associated with two capillary beds Glomerulus Peritubular capillaries Juxtamedullary nephrons also associated with Vasa recta © 2013 Pearson Education, Inc.

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.

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.

Vasa recta Long, thin-walled vessels parallel to long nephron loops of juxtamedullary nephrons Arise from efferent arterioles serving juxtamedullary nephrons Instead of peritubular capillaries Function in formation 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.

Juxtaglomerular Complex (JGC)
One per nephron Involves modified portions of Distal portion of ascending limb of nephron loop Afferent (sometimes efferent) arteriole Important in regulation of rate of filtrate formation and blood pressure © 2013 Pearson Education, Inc.

Three cell populations Macula densa, granular cells, extraglomerular mesangial cells Macula densa Tall, closely packed cells of ascending limb Chemoreceptors; sense NaCl content of filtrate © 2013 Pearson Education, Inc.

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
180 L fluid processed daily; only 1.5 L  urine Three processes in urine formation and adjustment of blood composition Glomerular filtration Tubular reabsorption Tubular secretion © 2013 Pearson Education, Inc.

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.

Kidneys filter body's entire plasma volume 60 times each day; consume 20-25% oxygen used by body at rest; produce urine from filtrate 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 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 25.10b The filtration membrane.
Filtration slits Podocyte cell body Foot processes Filtration slits between the podocyte foot processes © 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 engulfed by glomerular mesangial cells 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) – ( ) = 10 mm Hg © 2013 Pearson Education, Inc.

Glomerular Filtration Rate (GFR)
Volume of filtrate formed per minute by both kidneys (normal = 120–125 ml/min) GFR directly proportional to NFP – primary pressure is hydrostatic pressure in glomerulus Total surface area available for filtration – glomerular mesangial cells control by contracting Filtration membrane permeability – much more permeable than other capillaries © 2013 Pearson Education, Inc.

Regulation of Glomerular Filtration
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.

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 Take precedence over intrinsic controls if systemic BP < 80 or > 180 mm Hg © 2013 Pearson Education, Inc.

Maintains nearly constant GFR when MAP in range of 80–180 mm Hg
Intrinsic Controls Maintains nearly constant GFR when MAP in range of 80–180 mm Hg Autoregulation ceases if out of that range 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: 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.

Extrinsic Controls: Renin-Angiotensin- Aldosterone Mechanism
Main mechanism for increasing blood pressure – see Chapters 16 and 19 Three pathways to renin release by granular cells Direct stimulation of granular cells by sympathetic nervous system Stimulation by activated macula densa cells when filtrate NaCl concentration low Reduced stretch of granular cells © 2013 Pearson Education, Inc.

Extrinsic Controls: Other Factors Affecting GFR
Kidneys release chemicals; some act as paracrines that affect renal arterioles Adenosine Prostaglandin E2 Intrinsic angiotensin II – reinforces effects of hormonal angiotensin II © 2013 Pearson Education, Inc.

Most of tubular contents reabsorbed to blood
Tubular Reabsorption Most of tubular contents reabsorbed to blood Selective transepithelial process ~ All organic nutrients reabsorbed Water and ion reabsorption hormonally regulated and adjusted Includes active and passive tubular reabsorption Two routes Transcellular or paracellular © 2013 Pearson Education, Inc.

Tubular Reabsorption Transcellular route
Apical membrane of tubule cells  Cytosol of tubule cells  Basolateral membranes of tubule cells  Endothelium of peritubular capillaries © 2013 Pearson Education, Inc.

Tubular Reabsorption Paracellular route Between tubule cells
Limited by tight junctions, but leaky in proximal nephron Water, Ca2+, Mg2+, K+, and some Na+ in the PCT © 2013 Pearson Education, Inc.

The paracellular route involves: The transcellular route involves: 3
Figure Transcellular and paracellular routes of tubular reabsorption. Slide 1 Transport across the basolateral membrane. (Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces.) The paracellular route involves: The transcellular route involves: 3 • Movement through leaky tight junctions, particularly in the PCT. • Movement through the interstitial fluid and into the capillary. Transport across the apical membrane. 1 Diffusion through the cytosol. 2 Movement through the interstitial fluid and into the capillary. 4 Filtrate in tubule lumen Tubule cell Interstitial fluid Peri- tubular capillary Tight junction Lateral intercellular space 3 4 1 2 3 4 H2O and solutes Transcellular route Capillary endothelial cell Apical membrane Paracellular route H2O and solutes Basolateral membranes © 2013 Pearson Education, Inc.

Tubular Reabsorption of Sodium
Na+ - most abundant cation in filtrate Transport across basolateral membrane Primary active transport out of tubule cell by Na+-K+ ATPase pump  peritubular capillaries Transport across apical membrane Na+ passes through apical membrane by secondary active transport or facilitated diffusion mechanisms © 2013 Pearson Education, Inc.

Reabsorption of Nutrients, Water, and Ions
Na+ reabsorption by primary active transport provides energy and means for reabsorbing most other substances Creates electrical gradient  passive reabsorption of anions Organic nutrients reabsorbed by secondary active transport; cotransported with Na+ Glucose, amino acids, some ions, vitamins © 2013 Pearson Education, Inc.

Passive Tubular Reabsorption of Water
Movement of Na+ and other solutes creates osmotic gradient for water Water reabsorbed by osmosis, aided by water-filled pores called aquaporins Aquaporins always present in PCT  obligatory water reabsorption Aquaporins inserted in collecting ducts only if ADH present  facultative water reabsorption © 2013 Pearson Education, Inc.

Passive Tubular Reabsorption of Solutes
Solute concentration in filtrate increases as water reabsorbed  concentration gradients for solutes  Fat-soluble substances, some ions and urea, follow water into peritubular capillaries down concentration gradients  Lipid-soluble drugs, environmental pollutants difficult to excrete © 2013 Pearson Education, Inc.

Figure 25.14 Reabsorption by PCT cells.
Slide 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: 1 2 “Downhill” Na+ entry at the apical membrane. Reabsorption of organic nutrients and certain ions by cotransport at the apical membrane. 3 Filtrate in tubule lumen Nucleus Interstitial fluid Peri- tubular capillary Tubule cell 4 Reabsorption of water by osmosis through aquaporins. Water reabsorption increases the concentration of the solutes that are left behind. These solutes can then be reabsorbed as they move down their gradients: 2 Glucose Amino acids Some ions Vitamins 1 3 4 5 Lipid-soluble substances diffuse by the transcellular route. Lipid- soluble substances 5 Various Ions and urea 6 6 Various ions (e.g., Cl−, Ca2+, K+) and urea diffuse by the paracellular route. Tight junction Paracellular route Primary active transport Transport protein Secondary active transport Ion channel Passive transport (diffusion) Aquaporin © 2013 Pearson Education, Inc.

Most of tubular contents reabsorbed to blood
Tubular Reabsorption Most of tubular contents reabsorbed to blood Selective transepithelial process ~ All organic nutrients reabsorbed Water and ion reabsorption hormonally regulated and adjusted Includes active and passive tubular reabsorption Two routes Transcellular or paracellular © 2013 Pearson Education, Inc.

Transcellular transport systems specific and limited
Transport Maximum Transcellular transport systems specific and limited Transport maximum (Tm) for ~ every reabsorbed substance; reflects number of carriers in renal tubules available When carriers saturated, excess excreted in urine E.g., hyperglycemia  high blood glucose levels exceed Tm  glucose in urine © 2013 Pearson Education, Inc.

Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
PCT Site of most reabsorption All nutrients, e.g., glucose and amino acids 65% of Na+ and water Many ions ~ All uric acid; ½ urea (later secreted back into filtrate) © 2013 Pearson Education, Inc.

Nephron loop Descending limb - H2O can leave; solutes cannot Ascending limb – H2O cannot leave; solutes can Thin segment – passive Na+ movement Thick segment – Na+-K+-2Cl- symporter and Na+-H+ antiporter; some passes by paracellular route © 2013 Pearson Education, Inc.

DCT and collecting duct Reabsorption hormonally regulated Antidiuretic hormone (ADH) – Water Aldosterone – Na+ (therefore water) Atrial natriuretic peptide (ANP) – Na+ PTH – Ca2+ © 2013 Pearson Education, Inc.

Antidiuretic hormone (ADH) Released by posterior pituitary gland Causes principal cells of collecting ducts to insert aquaporins in apical membranes  water reabsorption As ADH levels increase  increased water reabsorption © 2013 Pearson Education, Inc.

Aldosterone Targets collecting ducts (principal cells) and distal DCT Promotes synthesis of apical Na+ and K+ channels, and basolateral Na+-K+ ATPases for Na+ reabsorption; water follows  little Na+ leaves body; aldosterone absence  loss of 2% filtered Na+ daily - incompatible with life Functions – increase blood pressure; decrease K+ levels © 2013 Pearson Education, Inc.

Atrial natriuretic peptide Reduces blood Na+  decreased blood volume and blood pressure Released by cardiac atrial cells if blood volume or pressure elevated Parathyroid hormone acts on DCT to increase Ca2+ reabsorption © 2013 Pearson Education, Inc.

Reabsorption in reverse; almost all in PCT
Tubular Secretion Reabsorption in reverse; almost all in PCT Selected substances K+, H+, NH4+, creatinine, organic acids and bases move from peritubular capillaries through tubule cells into filtrate Substances synthesized in tubule cells also secreted – e.g., HCO3- © 2013 Pearson Education, Inc.

Disposes of substances (e.g., drugs) bound to plasma proteins
Tubular Secretion Disposes of substances (e.g., drugs) bound to plasma proteins Eliminates undesirable substances passively reabsorbed (e.g., urea and uric acid) Rids body of excess K+ (aldosterone effect) Controls blood pH by altering amounts of H+ or HCO3– in urine © 2013 Pearson Education, Inc.

Figure 25.15 Summary of tubular reabsorption and secretion.
Cortex 65% of filtrate volume reabsorbed • H2O • Na+, HCO3−, and many other ions • Glucose, amino acids, and other nutrients Regulated reabsorption • Na+ (by aldosterone; Cl− follows) • Ca2+ (by parathyroid hormone) • H+ and NH4+ • Some drugs Regulated secretion • K+ (by aldosterone) Outer medulla Regulated reabsorption • H2O (by ADH) • Na+ (by aldosterone; Cl− follows) • Urea (increased by ADH) • Urea Regulated secretion • K+ (by aldosterone) Inner medulla • Reabsorption or secretion to maintain blood pH described in Chapter 26; involves H+, HCO3−, and NH4+ Reabsorption Secretion © 2013 Pearson Education, Inc.

Regulation of Urine Concentration and Volume
Osmolality Number of solute particles in 1 kg of H2O Reflects ability to cause osmosis © 2013 Pearson Education, Inc.

Regulation of Urine Concentration and Volume
Osmolality of body fluids Expressed in milliosmols (mOsm) Kidneys maintain osmolality of plasma at ~300 mOsm by regulating urine concentration and volume Kidneys regulate with countercurrent mechanism © 2013 Pearson Education, Inc.

Countercurrent Mechanism
Occurs when fluid flows in opposite directions in two adjacent segments of same tube with hair pin turn Countercurrent multiplier – interaction of filtrate flow in ascending/descending limbs of nephron loops of juxtamedullary nephrons Countercurrent exchanger - Blood flow in ascending/descending limbs of vasa recta © 2013 Pearson Education, Inc.

Countercurrent Mechanism
Role of countercurrent mechanisms Establish and maintain osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through medulla Allow kidneys to vary urine concentration © 2013 Pearson Education, Inc.

The three key players and their orientation in the osmotic gradient:
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 three key players and their orientation in the osmotic gradient: (c) The collecting ducts of all nephrons use the gradient to adjust urine osmolality. 300 300 400 (a) The long nephron loops of juxtamedullary nephrons create the gradient. They act as countercurrent multipliers. 600 The osmolality of the medullary interstitial fluid progressively increases from the 300 mOsm of normal body fluid to 1200 mOsm at the deepest part of the medulla. 900 (b) The vasa recta preserve the gradient. They act as countercurrent exchangers. 1200 © 2013 Pearson Education, Inc.

Countercurrent Multiplier: Nephron Loop
Descending limb Freely permeable to H2O H2O passes out of filtrate into hyperosmotic medullary interstitial fluid Filtrate osmolality increases to ~1200 mOsm © 2013 Pearson Education, Inc.

Countercurrent Multiplier: Nephron Loop
Ascending limb Impermeable to H2O Selectively permeable to solutes Na+ and Cl– actively reabsorbed in thick segment; some passively reabsorbed in thin segment Filtrate osmolality decreases to 100 mOsm © 2013 Pearson Education, Inc.

The Countercurrent Multiplier
Constant 200 mOsm difference between two limbs of nephron loop and between ascending limb and interstitial fluid Difference "multiplied" along length of loop to ~ 900 mOsm © 2013 Pearson Education, Inc.

The Countercurrent Exchanger
Vasa recta Preserve medullary gradient Prevent rapid removal of salt from interstitial space Remove reabsorbed water Water entering ascending vasa recta either from descending vasa recta or reabsorbed from nephron loop and collecting duct  Volume of blood at end of vasa recta greater than at beginning © 2013 Pearson Education, Inc.

Long nephron loops of juxtamedullary nephrons create the gradient.
Figure 25.16a Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. (2 of 4) Long nephron loops of juxtamedullary nephrons create the gradient. The countercurrent multiplier depends on three properties of the nephron loop to establish the osmotic gradient. Fluid flows in the opposite direction (countercurrent) through two adjacent parallel sections of a nephron loop. The descending limb is permeable to water, but not to salt. The ascending limb is impermeable to water, and pumps out salt. © 2013 Pearson Education, Inc.

Osmolality of filtrate Osmolality of filtrate entering the ascending
Figure 25.16a Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. (3 of 4) Long nephron loops of juxtamedullary nephrons create the gradient. These properties establish a positive feedback cycle that uses the flow of fluid to multiply the power of the salt pumps. Interstitial fluid osmolality Start here Water leaves the descending limb Salt is pumped out of the ascending limb Osmolality of filtrate in descending limb Osmolality of filtrate entering the ascending limb © 2013 Pearson Education, Inc.

Figure 25.16a Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. (4 of 4) (continued) As water and solutes are reabsorbed, the loop first concentrates the filtrate, then dilutes it. Active transport Passive transport Water impermeable 300 300 100 Cortex 100 300 300 Filtrate entering the nephron loop is isosmotic to both blood plasma and cortical interstitial fluid. 1 5 Filtrate is at its most dilute as it leaves the nephron loop. At 100 mOsm, it is hypo-osmotic to the interstitial fluid. 400 400 200 Na+ and Cl- are pumped out of the filtrate. This increases the interstitial fluid osmolality. 4 Outer medulla Osmolality of interstitial fluid (mOsm) 600 600 400 Water moves out of the filtrate in the descending limb down its osmotic gradient. This concentrates the filtrate. 2 900 900 700 Filtrate reaches its highest concentration at the bend of the loop. 3 Inner medulla Nephron loop 1200 1200 © 2013 Pearson Education, Inc.

Vasa recta preserve the gradient.
Figure 25.16b Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. Vasa recta preserve the gradient. The entire length of the vasa recta is highly permeable to water and solutes. Due to countercurrent exchanges between each section of the vasa recta and its surrounding interstitial fluid, the 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. Blood from efferent arteriole To vein 300 325 300 400 The countercurrent flow of fluid moves through two adjacent parallel sections of the vasa recta. 400 600 600 900 900 1200 Vasa recta © 2013 Pearson Education, Inc.

Osmolality of interstitial fluid (mOsm)
Figure 25.16c Juxtamedullary nephrons create an osmotic gradient within the renal medulla that allows the kidney to produce urine of varying concentration. Collecting ducts use the gradient. Under the control of antidiuretic hormone, the collecting ducts determine the final concentration and volume of urine. This process is fully described in Figure Collecting duct 300 400 Osmolality of interstitial fluid (mOsm) 600 900 1200 Urine © 2013 Pearson Education, Inc.

Formation of Dilute or Concentrated Urine
Osmotic gradient used to raise urine concentration > 300 mOsm to conserve water Overhydration  large volume dilute urine ADH production ; urine ~ 100 mOsm If aldosterone present, additional ions removed  ~ 50 mOsm Dehydration  small volume concentrated urine Maximal ADH released; urine ~ 1200 mOsm Severe dehydration – 99% water reabsorbed © 2013 Pearson Education, Inc.

Figure 25.17 Mechanism for forming 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 H2O reabsorption from collecting duct H2O reabsorption from collecting duct Large volume of dilute urine Small volume of concentrated urine Collecting duct Collecting duct Descending limb of nephron loop 300 Descending limb of nephron loop 300 100 100 150 DCT 100 DCT 300 Cortex Cortex 300 100 300 300 100 300 300 400 600 400 Osmolality of interstitial fluid (mOsm) 600 600 400 Osmolality of interstitial fluid (mOsm) 600 600 100 Outer medulla Outer medulla Urea 900 700 900 900 700 900 900 Urea Urea Inner medulla Inner medulla 1200 100 1200 1200 1200 1200 Large volume of dilute urine Small volume of concentrated urine Urea contributes to the osmotic gradient. ADH increases its recycling. Active transport Passive transport © 2013 Pearson Education, Inc.

Urea Recycling and the Medullary Osmotic Gradient
Urea helps form medullary gradient Enters filtrate in ascending thin limb of nephron loop by facilitated diffusion Cortical collecting duct reabsorbs water; leaves urea In deep medullary region now highly concentrated urea  interstitial fluid of medulla  back to ascending thin limb  high osmolality in medulla © 2013 Pearson Education, Inc.

Chemicals that enhance urinary output
Diuretics Chemicals that enhance urinary output ADH inhibitors, e.g., alcohol Na+ reabsorption inhibitors (and resultant H2O reabsorption), e.g., caffeine, drugs for hypertension or edema Loop diuretics inhibit medullary gradient formation Osmotic diuretics - substance not reabsorbed so water remains in urine, e.g., high glucose of diabetic patient © 2013 Pearson Education, Inc.

Clinical Evaluation of Kidney Function
Urine examined for signs of disease Assessing renal function requires both blood and urine examination © 2013 Pearson Education, Inc.

Volume of plasma kidneys clear of particular substance in given time
Renal Clearance Volume of plasma kidneys clear of particular substance in given time Renal clearance tests used to determine GFR To detect glomerular damage To follow progress of renal disease © 2013 Pearson Education, Inc.

Renal Clearance C = UV/P C = renal clearance rate (ml/min)
U = concentration (mg/ml) of substance in urine V = flow rate of urine formation (ml/min) P = concentration of same substance in plasma © 2013 Pearson Education, Inc.

Renal Clearance Inulin (plant polysaccharide) is standard used
Freely filtered; neither reabsorbed nor secreted by kidneys; its renal clearance = GFR = 125 ml/min If C < 125 ml/min, substance reabsorbed If C = 0, substance completely reabsorbed, or not filtered If C = 125 ml/min, no net reabsorption or secretion If C > 125 ml/min, substance secreted (most drug metabolites) © 2013 Pearson Education, Inc.

Chronic renal disease - GFR < 60 ml/min for 3 months E.g., in diabetes mellitus; hypertension Renal failure – GFR < 15 ml/min Causes uremia – ionic and hormonal imbalances; metabolic abnormalities; toxic molecule accumulation Treated with hemodialysis or transplant © 2013 Pearson Education, Inc.

Physical Characteristics of Urine
Color and transparency Clear Cloudy may indicate urinary tract infection Pale to deep yellow from urochrome Pigment from hemoglobin breakdown; more concentrated urine  deeper color Abnormal color (pink, brown, smoky) Food ingestion, bile pigments, blood, drugs © 2013 Pearson Education, Inc.

Slightly acidic (~pH 6, with range of 4.5 to 8.0) Acidic diet (protein, whole wheat)   pH Alkaline diet (vegetarian), prolonged vomiting, or urinary tract infections  pH Specific gravity 1.001 to 1.035; dependent on solute concentration © 2013 Pearson Education, Inc.

Chemical Composition of Urine
95% water and 5% solutes Nitrogenous wastes Urea (from amino acid breakdown) – largest solute component Uric acid (from nucleic acid metabolism) Creatinine (metabolite of creatine phosphate) © 2013 Pearson Education, Inc.

Chemical Composition of Urine
Other normal solutes Na+, K+, PO43–, and SO42–, Ca2+, Mg2+ and HCO3– Abnormally high concentrations of any constituent, or abnormal components, e.g., blood proteins, WBCs, bile pigments, may indicate pathology © 2013 Pearson Education, Inc.

Urine transport, Storage, and Elimination: Ureters
Convey urine from kidneys to bladder Begin at L2 as continuation of renal pelvis Retroperitoneal Enter base of bladder through posterior wall As bladder pressure increases, distal ends of ureters close, preventing backflow of urine © 2013 Pearson Education, Inc.

Three layers of ureter wall from inside out
Ureters Three layers of ureter wall from inside out Mucosa - transitional epithelium Muscularis – smooth muscle sheets Contracts in response to stretch Propels urine into bladder Adventitia – outer fibrous connective tissue © 2013 Pearson Education, Inc.

Figure 25.19 Cross-sectional view of the ureter wall (10x).
Lumen Mucosa • Transitional epithelium • Lamina propria Muscularis • Longitudinal Layer • Circular layer Adventitia © 2013 Pearson Education, Inc.

Renal calculi - kidney stones in renal pelvis Crystallized calcium, magnesium, or uric acid salts Large stones block ureter  pressure & pain May be due to chronic bacterial infection, urine retention, Ca2+ in blood, pH of urine Treatment - shock wave lithotripsy – noninvasive; shock waves shatter calculi © 2013 Pearson Education, Inc.

Muscular sac for temporary storage of urine
Urinary Bladder Muscular sac for temporary storage of urine Retroperitoneal, on pelvic floor posterior to pubic symphysis Males—prostate inferior to bladder neck Females—anterior to vagina and uterus © 2013 Pearson Education, Inc.

Openings for ureters and urethra Trigone
Urinary Bladder Openings for ureters and urethra Trigone Smooth triangular area outlined by openings for ureters and urethra Infections tend to persist in this region © 2013 Pearson Education, Inc.

Urinary Bladder Layers of bladder wall
Mucosa - transitional epithelial mucosa Thick detrusor - three layers of smooth muscle Fibrous adventitia (peritoneum on superior surface only) © 2013 Pearson Education, Inc.

Collapses when empty; rugae appear
Urinary Bladder Collapses when empty; rugae appear Expands and rises superiorly during filling without significant rise in internal pressure ~ Full bladder 12 cm long; holds ~ 500 ml Can hold ~ twice that if necessary Can burst if overdistended © 2013 Pearson Education, Inc.

Kidney Renal pelvis Ureter Urinary bladder
Figure Pyelogram. Kidney Renal pelvis Ureter Urinary bladder © 2013 Pearson Education, Inc.

Figure 25.20a Structure of the urinary bladder and urethra.
Peritoneum Ureter Rugae Detrusor Adventitia Ureteric orifices Trigone of bladder Bladder neck Internal urethral sphincter Prostate Prostatic urethra Intermediate part of the urethra External urethral sphincter Urogenital diaphragm Spongy urethra Erectile tissue of penis External urethral orifice Male. The long male urethra has three regions: prostatic, intermediate, and spongy. © 2013 Pearson Education, Inc.

Figure 25.20b Structure of the urinary bladder and urethra.
Peritoneum Ureter Rugae Detrusor Ureteric orifices Bladder neck Internal urethral sphincter Trigone External urethral sphincter Urogenital diaphragm Urethra External urethral orifice Female. © 2013 Pearson Education, Inc.

Muscular tube draining urinary bladder
Urethra Muscular tube draining urinary bladder Lining epithelium Mostly pseudostratified columnar epithelium, except Transitional epithelium near bladder Stratified squamous epithelium near external urethral orifice © 2013 Pearson Education, Inc.

Urethra Sphincters Internal urethral sphincter
Involuntary (smooth muscle) at bladder-urethra junction Contracts to open External urethral sphincter Voluntary (skeletal) muscle surrounding urethra as it passes through pelvic floor © 2013 Pearson Education, Inc.

Urethra Female urethra (3–4 cm) Tightly bound to anterior vaginal wall
External urethral orifice Anterior to vaginal opening; posterior to clitoris © 2013 Pearson Education, Inc.

Figure 25.20b Structure of the urinary bladder and urethra.
Peritoneum Ureter Rugae Detrusor Ureteric orifices Bladder neck Internal urethral sphincter Trigone External urethral sphincter Urogenital diaphragm Urethra External urethral orifice Female. © 2013 Pearson Education, Inc.

Male urethra carries semen and urine
Three named regions Prostatic urethra (2.5 cm)—within prostate Intermediate part of the urethra (membranous urethra) (2 cm)—passes through urogenital diaphragm from prostate to beginning of penis Spongy urethra (15 cm)—passes through penis; opens via external urethral orifice © 2013 Pearson Education, Inc.

Figure 25.20a Structure of the urinary bladder and urethra.
Peritoneum Ureter Rugae Detrusor Adventitia Ureteric orifices Trigone of bladder Bladder neck Internal urethral sphincter Prostate Prostatic urethra Intermediate part of the urethra External urethral sphincter Urogenital diaphragm Spongy urethra Erectile tissue of penis External urethral orifice Male. The long male urethra has three regions: prostatic, intermediate, and spongy. © 2013 Pearson Education, Inc.

Three simultaneous events must occur
Micturition Urination or voiding Three simultaneous events must occur Contraction of detrusor by ANS Opening of internal urethral sphincter by ANS Opening of external urethral sphincter by somatic nervous system © 2013 Pearson Education, Inc.

Reflexive urination (urination in infants)
Micturition Reflexive urination (urination in infants) Distension of bladder activates stretch receptors Excitation of parasympathetic neurons in reflex center in sacral region of spinal cord Contraction of detrusor Contraction (opening) of internal sphincter Inhibition of somatic pathways to external sphincter, allowing its relaxation (opening) © 2013 Pearson Education, Inc.

Pontine control centers mature between ages 2 and 3
Micturition Pontine control centers mature between ages 2 and 3 Pontine storage center inhibits micturition Inhibits parasympathetic pathways Excites sympathetic and somatic efferent pathways Pontine micturition center promotes micturition Excites parasympathetic pathways Inhibits sympathetic and somatic efferent pathways © 2013 Pearson Education, Inc.

Figure 25.21 Control of micturition.
Brain Higher brain centers Urinary bladder fills, stretching bladder wall Allow or inhibit micturition as appropriate Afferent impulses from stretch receptors Pontine micturition center Pontine storage center Simple spinal reflex Promotes micturition by acting on all three spinal efferents Inhibits micturition by acting on all three Spinal efferents Spinal cord Spinal cord Parasympathetic activity Sympathetic activity Somatic motor nerve activity Parasympathetic activity Sympathetic activity Somatic motor nerve activity Detrusor contracts; internal urethral sphincter opens External urethral sphincter opens Inhibits Micturition © 2013 Pearson Education, Inc.

Incontinence usually from weakened pelvic muscles Stress incontinence Increased intra-abdominal pressure forces urine through external sphincter Overflow incontinence Urine dribbles when bladder overfills © 2013 Pearson Education, Inc.

Developmental Aspects
Three sets of embryonic kidneys form in succession Pronephros degenerates but pronephric duct persists Mesonephros claims this duct; becomes mesonephric duct Metanephros develop by fifth week, develops into adult kidneys and ascends © 2013 Pearson Education, Inc.

Figure 25.22a Development of the urinary system in the embryo.
Degenerating pronephros Developing digestive tract Urogenital ridge Duct to yolk sac Mesonephros Allantois Cloaca Mesonephric duct (initially, pronephric duct) Ureteric bud Hindgut Week 5 © 2013 Pearson Education, Inc.

Figure 25.22b Development of the urinary system in the embryo.
Degenerating pronephros Duct to yolk sac Allantois Body stalk Urogenital sinus Rectum Mesonephros Ureteric bud Mesonephric duct Metanephros Week 6 © 2013 Pearson Education, Inc.

Metanephros develops as ureteric buds that induce mesoderm of urogenital ridge to form nephrons Distal ends of ureteric buds form renal pelves, calyces, and collecting ducts Proximal ends become ureters Kidneys excrete urine into amniotic fluid by third month Cloaca subdivides into rectum, anal canal, and urogenital sinus © 2013 Pearson Education, Inc.

Figure 25.22c Development of the urinary system in the embryo.
Urogenital sinus (developing urinary bladder) Gonad Rectum Metanephros (kidney) Week 7 © 2013 Pearson Education, Inc.

Figure 25.22d Development of the urinary system in the embryo.
Urinary bladder Gonad Urethra Kidney Anus Ureter Rectum Week 8 © 2013 Pearson Education, Inc.

Three common congenital abnormalities Horseshoe kidney Two kidneys fuse across midline  single U-shaped kidney; usually asymptomatic Hypospadias Urethral orifice on ventral surface of penis Corrected surgically at ~ 12 months © 2013 Pearson Education, Inc.

Polycystic kidney disease Many fluid-filled cysts interfere with function Autosomal dominant form – less severe but more common Autosomal recessive – more severe Cause unknown but involves defect in signaling proteins © 2013 Pearson Education, Inc.

Frequent micturition in infants due to small bladders and less-concentrated urine Incontinence normal in infants: control of voluntary urethral sphincter develops with nervous system E. coli bacteria account for 80% of all urinary tract infections Untreated childhood streptococcal infections may cause long-term renal damage Sexually transmitted diseases can also inflame urinary tract © 2013 Pearson Education, Inc.

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 © 2013 Pearson Education, Inc.

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