Chapter 26: The Urinary System

Chapter 26: The Urinary System
Copyright 2009, John Wiley & Sons, Inc.

Overview of kidney functions
Regulation of blood ionic composition Regulation of blood pH Regulation of blood volume Regulation of blood pressure Maintenance of blood osmolarity Production of hormones (calcitrol and erythropoitin) Regulation of blood glucose level Excretion of wastes from metabolic reactions and foreign substances (drugs or toxins) Copyright 2009, John Wiley & Sons, Inc.

Anatomy and histology of the kidneys
External anatomy Renal hilium – indent where ureter emerges along with blood vessels, lymphatic vessels and nerves 3 layers of tissue Renal capsule – deep layer – continuous with outer coat of ureter, barrier against trauma, maintains kidney shape Adipose capsule – mass of fatty tissue that protects kidney from trauma and holds it in place Renal fascia – superficial layer – thin layer of connective tissue that anchors kidney to surrounding structures and abdominal wall Copyright 2009, John Wiley & Sons, Inc.

Organs of the urinary system in a female

Position and coverings of the kidneys

Copyright 2009, John Wiley & Sons, Inc.
Internal anatomy Renal cortex – superficial Outer cortical zone Inner juxtamedullary zone Renal columns – portions of cortex that extend between renal pyramids Renal medulla – inner region Several cone shaped renal pyramids – base faces cortex and renal papilla points toward hilium Renal lobe – renal pyramid, overlying cortex area, and ½ of each adjacent renal column Copyright 2009, John Wiley & Sons, Inc.

Anatomy of the kidneys Parenchyma (functional portion) of kidney Renal cortex and renal pyramids of medulla Nephron – microscopic functional units of kidney Urine formed by nephron drains into Papillary ducts Minor and major calyces Renal pelvis Ureter Urinary bladder Copyright 2009, John Wiley & Sons, Inc.

Internal anatomy of the kidneys

Blood and nerve supply of the kidneys
Blood supply Although kidneys constitute less than 0.5% of total body mass, they receive 20-25% of resting cardiac output Left and right renal artery enters kidney Branches into segmental, interlobar, arcuate, interlobular arteries Each nephron receives one afferent arteriole Divides into glomerulus – capillary ball Reunite to form efferent arteriole (unique) Divide to form peritubular capillaries or some have vasa recta Peritubular venule, interlobar vein and renal vein exits kidney Renal nerves are part of the sympathetic autonomic nervous system Most are vasomotor nerves regulating blood flow Copyright 2009, John Wiley & Sons, Inc.

Blood supply of the kidneys

The nephron – functional units of kidney
2 parts Renal corpuscle – filters blood plasma Glomerulus – capillary network Glomerular (Bowman’s) capsule – double-walled cup surrounding glomerulus Renal tubule – filtered fluid passes into Proximal convoluted tubule Descending and ascending loop of Henle (nephron loop) Distal convoluted tubule Copyright 2009, John Wiley & Sons, Inc.

Nephrons Renal corpuscle and both convoluted tubules in cortex, loop of Henle extend into medulla Distal convoluted tubule of several nephrons empty into single collecting duct Cortical nephrons – 80-85% of nephrons Renal corpuscle in outer portion of cortex and short loops of Henle extend only into outer region of medulla Juxtamedullary nephrons – other 25-20% Renal corpuscle deep in cortex and long loops of Henle extend deep into medulla Receive blood from peritubular capillaries and vasa recta Ascending limb has thick and thin regions Enable kidney to secrete very dilute or very concentrated urine Copyright 2009, John Wiley & Sons, Inc.

The structure of nephrons and associated blood vessels

Histology of nephron and collecting duct
Glomerular capsule Visceral layer has podocytes that wrap projections around single layer of endothelial cells of glomerular capillaries and form inner wall of capsule Parietal layer forms outer wall of capsule Fluid filtered from glomerular capillaries enters capsular (Bowman’s) space Copyright 2009, John Wiley & Sons, Inc.

Histology of a renal corpuscle

Renal tubule and collecting duct
Proximal convoluted tubule cells have microvilli with brush border – increases surface area Juxtaglomerular appraratus helps regulate blood pressure in kidney Macula densa – cells in final part of ascending loop of Henle Juxtaglomerular cells – cells of afferent and efferent arterioles contain modified smooth muscle fibers Last part of distal convoluted tubule and collecting duct Principal cells – receptors for antidiuretic hormone (ADH) and aldosterone Intercalated cells – role in blood pH homeostasis Copyright 2009, John Wiley & Sons, Inc.

Overview of renal physiology
Glomerular filtration Water and most solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubule Tubular reabsorption As filtered fluid moves along tubule and through collecting duct, about 99% of water and many useful solutes reabsorbed – returned to blood Tubular secretion As filtered fluid moves along tubule and through collecting duct, other material secreted into fluid such as wastes, drugs, and excess ions – removes substances from blood Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted Excretion of any solute = glomerular filtration + secretion - reabsorption Copyright 2009, John Wiley & Sons, Inc.

Structures and functions of a nephron
Renal corpuscle Renal tubule and collecting duct Peritubular capillaries Urine (contains excreted substances) Blood reabsorbed Tubular secretion from blood into fluid Tubular reabsorption from fluid into blood Fluid in renal tubule Afferent arteriole Filtration from blood plasma into nephron Efferent Glomerular capsule 1 2 3 Renal corpuscle Renal tubule and collecting duct Peritubular capillaries Urine (contains excreted substances) Blood reabsorbed Tubular reabsorption from fluid into blood Fluid in renal tubule Afferent arteriole Filtration from blood plasma into nephron Efferent Glomerular capsule 1 2 Renal corpuscle Renal tubule and collecting duct Peritubular capillaries Urine (contains excreted substances) Blood reabsorbed Fluid in renal tubule Afferent arteriole Filtration from blood plasma into nephron Efferent Glomerular capsule 1 Copyright 2009, John Wiley & Sons, Inc.

Glomerular filtration
Glomerular filtrate – fluid that enters capsular space Daily volume liters – more than 99% returned to blood plasma via tubular reabsorption Filtration membrane – endothelial cells of glomerular capillaries and podocytes encircling capillaries Permits filtration of water and small solutes Prevents filtration of most plasma proteins, blood cells and platelets 3 barriers to cross – glomerular endothelial cells fenestrations, basal lamina between endothelium and podocytes and pedicels of podocytes create filtration slits Volume of fluid filtered is large because of large surface area, thin and porous membrane, and high glomerular capillary blood pressure Copyright 2009, John Wiley & Sons, Inc.

The filtration membrane

Filtration slit Pedicel of podocyte Fenestration (pore) of glomerular endothelial cell Basal lamina Lumen of glomerulus (b) Filtration membrane TEM 78,000x (a) Details of filtration membrane Pedicel Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through Basal lamina of glomerulus: prevents filtration of larger proteins Slit membrane between pedicels: prevents filtration of medium-sized proteins Podocyte of visceral layer of glomerular (Bowman’s) capsule 1 2 3 Filtration slit Pedicel of podocyte Fenestration (pore) of glomerular endothelial cell Basal lamina Lumen of glomerulus (b) Filtration membrane TEM 78,000x (a) Details of filtration membrane Pedicel Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through Basal lamina of glomerulus: prevents filtration of larger proteins Podocyte of visceral layer of glomerular (Bowman’s) capsule 1 2 Filtration slit Pedicel of podocyte Fenestration (pore) of glomerular endothelial cell Basal lamina Lumen of glomerulus (b) Filtration membrane TEM 78,000x (a) Details of filtration membrane Pedicel Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through Podocyte of visceral layer of glomerular (Bowman’s) capsule 1

Net filtration pressure
Net filtration pressure (NFP) is the total pressure that promotes filtration NFP = GBHP – CHP – BCOP Glomerular blood hydrostatic pressure is the blood pressure of the glomerular capillaries forcing water and solutes through filtration slits Capsular hydrostatic pressure is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and represents “back pressure” Blood colloid osmotic pressure due to presence of proteins in blood plasma and also opposes filtration Copyright 2009, John Wiley & Sons, Inc.

The pressures that drive glomerular filtration

NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg BLOOD COLLOID OSMOTIC PRESSURE (BCOP) = 30 mmHg CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg Capsular space Glomerular (Bowman's) capsule Efferent arteriole Afferent arteriole 1 2 3 Proximal convoluted tubule NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg Capsular space Glomerular (Bowman's) capsule Efferent arteriole Afferent arteriole 1 2 Proximal convoluted tubule NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg Capsular space Glomerular (Bowman's) capsule Efferent arteriole Afferent arteriole 1 Proximal convoluted tubule

Glomerular filtration
Glomerular filtration rate – amount of filtrate formed in all the renal corpuscles of both kidneys each minute Homeostasis requires kidneys maintain a relatively constant GFR Too high – substances pass too quickly and are not reabsorbed Too low – nearly all reabsorbed and some waste products not adequately excreted GFR directly related to pressures that determine net filtration pressure Copyright 2009, John Wiley & Sons, Inc.

3 Mechanisms regulating GFR
Renal autoregulation Kidneys themselves maintain constant renal blood flow and GFR using Myogenic mechanism – occurs when stretching triggers contraction of smooth muscle cells in afferent arterioles – reduces GFR Tubuloglomerular mechanism – macula densa provides feedback to glomerulus, inhibits release of NO causing afferent arterioles to constrict and decreasing GFR Copyright 2009, John Wiley & Sons, Inc.

Tuboglomerular feedback

Mechanisms regulating GFR
Neural regulation Kidney blood vessels supplied by sympathetic ANS fibers that release norepinephrine causing vasoconstriction Moderate stimulation – both afferent and efferent arterioles constrict to same degree and GFR decreases Greater stimulation constricts afferent arterioles more and GFR drops Hormonal regulation Angiotensin II reduces GFR – potent vasoconstrictor of both afferent and efferent arterioles Atrial natriuretic peptide increases GFR – stretching of atria causes release, increases capillary surface area for filtration Copyright 2009, John Wiley & Sons, Inc.

Tubular reabsorption and tubular secretion
Reabsorption – return of most of the filtered water and many solutes to the bloodstream About 99% of filtered water reabsorbed Proximal convoluted tubule cells make largest contribution Both active and passive processes Secretion – transfer of material from blood into tubular fluid Helps control blood pH Helps eliminate substances from the body Copyright 2009, John Wiley & Sons, Inc.

Reabsorption routes and transport mechanisms
Paracellular reabsorption Between adjacent tubule cells Tight junction do not completely seal off interstitial fluid from tubule fluid Passive Transcellular reabsorption – through an individual cell Transport mechanisms Reabsorption of Na+ especially important Primary active transport Sodium-potassium pumps in basolateral membrane only Secondary active transport Symporters, antiporters Transport maximum (Tm) Upper limit to how fast it can work Obligatory vs. facultative water reabsorption Copyright 2009, John Wiley & Sons, Inc.

Reabsorption and secretion in proximal convoluted tubule (PCT)
Largest amount of solute and water reabsorption Secretes variable amounts of H+, NH4+ and urea Most solute reabsorption involves Na+ Symporters for glucose, amino acids, lactic acid, water-soluble vitamins, phosphate and sulfate Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be secreted Solute reabsorption promotes osmosis – creates osmotic gradient Aquaporin-1 in cells lining PCT and descending limb of loop of Henle As water leaves tubular fluid, solute concentration increases Urea and ammonia in blood are filtered at glomerulus and secreted by proximal convoluted tubule cells Copyright 2009, John Wiley & Sons, Inc.

Reabsorption and secretion in the proximal convoluted tubule

Reabsorption in the loop of Henle
Chemical composition of tubular fluid quite different from filtrate Glucose, amino acids and other nutrients reabsorbed Osmolarity still close to that of blood Reabsorption of water and solutes balanced For the first time reabsorption of water is NOT automatically coupled to reabsorption of solutes Independent regulation of both volume and osmolarity of body fluids Na+-K+-2Cl- symporters function in Na+ and Cl- reabsorption – promotes reabsorption of cations Little or no water is reabsorbed in ascending limb – osmolarity decreases Copyright 2009, John Wiley & Sons, Inc.

Na+–K+-2Cl- symporter in the thick ascending limb of the loop of Henle

Reabsorption and secretion in the late distale convoluted tubule and collecting duct Reabsorption on the early distal convoluted tubule Na+-Cl- symporters reabsorb Na+ and Cl- Major site where parathyroid hormone stimulates reabsorption of Ca+ depending on body’s needs Reabsorption and secretion in the late distal convoluted tubule and collecting duct 90-95% of filtered solutes and fluid have been returned by now Principal cells reabsorb Na+ and secrete K+ Intercalated cells reabsorb K+ and HCO3- and secrete H+ Amount of water reabsorption and solute reabsorption and secretion depends on body’s needs Copyright 2009, John Wiley & Sons, Inc.

Hormonal regulation of tubular reabsorption and secretion
Angiotensin II - when blood volume and blood pressure decrease Decreases GFR, enhances reabsorption of Na+, Cl- and water in PCT Aldosterone - when blood volume and blood pressure decrease Stimulates principal cells in collecting duct to reabsorb more Na+ and Cl- and secrete more K+ Parathyroid hormone Stimulates cells in DCT to reabsorb more Ca2+ Copyright 2009, John Wiley & Sons, Inc.

Regulation of facultative water reabsorption by ADH
Antidiuretic hormone (ADH or vasopressin) Increases water permeability of cells by inserting aquaporin-2 in last part of DCT and collecting duct Atrial natriuretic peptide (ANP) Large increase in blood volume promotes release of ANP Decreases blood volume and pressure by inhibiting reabsorption of Na+ and water in PCT and collecting duct, suppress secretion of ADH and aldosterone Copyright 2009, John Wiley & Sons, Inc.

Production of dilute and concentrated urine
Even though your fluid intake can be highly variable, total fluid volume in your body remains stable Depends in large part on the kidneys to regulate the rate of water loss in urine ADH controls whether dilute or concentrated urine is formed Absent or low ADH = dilute urine Higher levels = more concentrated urine through increased water reabsorption Copyright 2009, John Wiley & Sons, Inc.

Formation of dilute urine
Glomerular filtrate has same osmolarity as blood 300 mOsm/liter Fluid leaving PCT is isotonic to plasma When dilute urine is being formed, the osmolarity of fluid increases as it goes down the descending loop of Henle, decreases as it goes up the ascending limb, and decreases still more as it flows through the rest of the nephron and collecting duct Copyright 2009, John Wiley & Sons, Inc.

Formation of dilute urine
Osmolarity of interstitial fluid of renal medulla becomes greater, more water is reabsorbed from tubular fluid so fluid become more concentrated Water cannot leave in thick portion of ascending limb but solutes leave making fluid more dilute than blood plasma Additional solutes but not much water leaves in DCT Low ADH makes late DCT and collecting duct have low water permeability Copyright 2009, John Wiley & Sons, Inc.

Formation of concentrated urine
Urine can be up to 4 times more concentrated than blood plasma Ability of ADH depends on presence of osmotic gradient in interstitial fluid of renal medulla 3 major solutes contribute – Na+, Cl-, and urea 2 main factors build and maintain gradient Differences in solute and water permeability in different sections of loop of Henle and collecting ducts Countercurrent flow of fluid though descending and ascending loop of Henle and blood through ascending and descending limbs of vasa recta Copyright 2009, John Wiley & Sons, Inc.

Countercurrent multiplication
Process by which a progressively increasing osmotic gradient is formed as a result of countercurrent flow Long loops of Henle of juxtamedullary nephrons function as countercurrent multiplier Symporters in thick ascending limb of loop of Henle cause buildup of Na+ and Cl- in renal medulla, cells impermeable to water Countercurrent flow establishes gradient as reabsorbed Na+ and Cl- become increasingly concentrated Cells in collecting duct reabsorb more water and urea Urea recycling causes a buildup of urea in the renal medulla Long loop of Henle establishes gradient by countercurrent multiplication Copyright 2009, John Wiley & Sons, Inc.

Countercurrent exchange
Process by which solutes and water are passively exchanged between blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow Vasa recta is a countercurrent exchanger Osmolarity of blood leaving vasa recta is only slightly higher than blood entering Provides oxygen and nutrients to medulla without washing out or diminishing gradient Vasa recta maintains gradient by countercurrent exchange Copyright 2009, John Wiley & Sons, Inc.

Mechanism of urine concentration in long-loop juxtamedullary nephrons

1 3 4 1 3 1 1 (b) Recycling of salts and urea in the vasa recta
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron Glomerular (Bowman’s) capsule Afferent arteriole Efferent Glomerulus Distal convoluted tubule Proximal convoluted tubule Symporters in thick ascending limb cause buildup of Na+ and Cl– Interstitial fluid in renal medulla 300 1200 1000 800 Osmotic gradient 600 400 H 2 O 200 980 780 580 380 100 Loop of Henle Concentrated urine 320 H2O Urea Papillary duct Urea recycling causes buildup of urea in the renal medulla Collecting Countercurrent flow through loop of Henle establishes an osmotic Principal cells in collecting duct reabsorb more water when ADH is present 500 700 900 1100 Na+CI– Blood flow Flow of tubular fluid Presense of Na+-K+-2CI– symporters Interstitial fluid in renal cortex Juxtamedullary nephron and its blood supply together Vasa recta Loop of Henle 1 3 4 (b) Recycling of salts and urea in the vasa recta (a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron Glomerular (Bowman’s) capsule Afferent arteriole Efferent Glomerulus Distal convoluted tubule Proximal convoluted tubule Symporters in thick ascending limb cause buildup of Na+ and Cl– Interstitial fluid in renal medulla 300 1200 1000 800 Osmotic gradient 600 400 H 2 O 200 980 780 580 380 100 Loop of Henle Concentrated urine 320 H2O Urea Papillary duct Collecting Countercurrent flow through loop of Henle establishes an osmotic Principal cells in collecting duct reabsorb more water when ADH is present 500 700 900 1100 Na+CI– Blood flow Flow of tubular fluid Presense of Na+-K+-2CI– symporters Interstitial fluid in renal cortex Juxtamedullary nephron and its blood supply together Vasa recta Loop of Henle 1 3 (b) Recycling of salts and urea in the vasa recta (a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron Glomerular (Bowman’s) capsule Afferent arteriole Efferent Glomerulus Distal convoluted tubule Proximal convoluted tubule Symporters in thick ascending limb cause buildup of Na+ and Cl– Interstitial fluid in renal medulla 300 1200 1000 800 Osmotic gradient 600 400 H 2 O 200 980 780 580 380 100 Loop of Henle Concentrated urine 320 H2O Urea Papillary duct Collecting Countercurrent flow through loop of Henle establishes an osmotic 500 700 900 1100 Na+CI– Blood flow Flow of tubular fluid Presense of Na+-K+-2CI– symporters Interstitial fluid in renal cortex Juxtamedullary nephron and its blood supply together Vasa recta Loop of Henle 1 (b) Recycling of salts and urea in the vasa recta (a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron Glomerular (Bowman’s) capsule Afferent arteriole Efferent Glomerulus Distal convoluted tubule Proximal convoluted tubule Symporters in thick ascending limb cause buildup of Na+ and Cl– Interstitial fluid in renal medulla 300 1200 1000 800 Osmotic gradient 600 400 H 2 O 200 980 780 580 380 100 Loop of Henle Concentrated urine 320 H2O Urea Papillary duct Collecting 500 700 900 1100 Na+CI– Blood flow Flow of tubular fluid Presense of Na+-K+-2CI– symporters Interstitial fluid in renal cortex Juxtamedullary nephron and its blood supply together Vasa recta Loop of Henle 1

Evaluation of kidney function
Urinalysis Analysis of the volume and physical, chemical and microscopic properties of urine Water accounts for 95% of total urine volume Typical solutes are filtered and secreted substances that are not reabsorbed If disease alters metabolism or kidney function, traces if substances normally not present or normal constituents in abnormal amounts may appear Copyright 2009, John Wiley & Sons, Inc.

Evaluation of kidney function
Blood tests Blood urea nitrogen (BUN) – measures blood nitrogen that is part of the urea resulting from catabolism and deamination of amino acids Plasma creatinine results from catabolism of creatine phosphate in skeletal muscle – measure of renal function Renal plasma clearance More useful in diagnosis of kidney problems than above Volume of blood cleared of a substance per unit time High renal plasma clearance indicates efficient excretion of a substance into urine PAH administered to measure renal plasma flow Copyright 2009, John Wiley & Sons, Inc.

Urine transportation, storage, and elimination
Ureters Each of 2 ureters transports urine from renal pelvis of one kidney to the bladder Peristaltic waves, hydrostatic pressure and gravity move urine No anatomical valve at the opening of the ureter into bladder – when bladder fills it compresses the opening and prevents backflow Copyright 2009, John Wiley & Sons, Inc.

Ireters, urinary bladder, and urethra in a female

Urinary bladder and urethra
Hollow, distensible muscular organ Capacity averages mL Micturition – discharge of urine from bladder Combination of voluntary and involuntary muscle contractions When volume increases stretch receptors send signals to micturition center in spinal cord triggering spinal reflex – micturition reflex In early childhood we learn to initiate and stop it voluntarily Urethra Small tube leading from internal urethral orifice in floor of bladder to exterior of the body In males discharges semen as well as urine Copyright 2009, John Wiley & Sons, Inc.

Comparison between female and male urethras

End of Chapter 26 Copyright 2009 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein. Copyright 2009, John Wiley & Sons, Inc.

Chapter 26: The Urinary System

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