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Chapter Notes for Lecture: E.N. Marieb, HUMAN ANATOMY & PHYSIOLOGY,5TH Edition, , Benjamine Cummings Publisher, 2001 Prepare from : V.A. Austin’s PowerPpoint Presentation (ISBN: 0-8053-5469-7), CD ROM: Pearson Education, Inc. , 2003.

 

The Urinary System

 

Urinary System Organs: Kidneys

•      Filter 200 liters of blood daily, allowing toxins, metabolic wastes, and excess ions to leave the body in urine

•      Regulate volume and chemical makeup of the blood

•      Maintain the proper balance between water and salts, and acids and bases

•      Produce renin to help regulate blood pressure and erythropoietin to stimulate red blood cell production

•      Activate vitamin D and produce glucose during prolonged fasting

Other Urinary System Organs

•      Urinary bladder – provides a temporary storage reservoir for urine

•      Paired ureters – transports urine from the kidneys to the bladder

•      Urethra – transports urine from the bladder out of the body

Location and External Anatomy

•      The bean-shaped kidneys lie in a retroperitoneal position in the superior lumbar region and extend from the twelfth thoracic to the third lumbar vertebrae

•      The right kidney is lower than the left because it is crowded by the liver

•      The lateral surface is convex and the medial surface is concave, with a vertical cleft called the renal hilus leading to the renal sinus

•      Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus

Kidney: Associated Structures

•      The functionally unrelated adrenal gland sits atop each kidney

•      Three supportive tissues surround the kidney

•    Renal capsule – adheres to the kidney surface and prevents infections in surrounding regions from spreading to the kidneys

•    Adipose capsule – cushions the kidney and helps attach it to the body wall

•    Renal fascia – dense fibrous connective tissue that anchors the kidney

Internal Anatomy

•      A frontal section shows three distinct regions

•    Cortex – the light colored, granular superficial region

•    Medulla – exhibits cone-shaped medullary (renal) pyramids

•   Pyramids are made up of parallel bundles of urine-collecting tubules

•   Renal columns are inward extensions of cortical tissue that separate the pyramids

•   The medullary pyramid and its surrounding capsule constitutes a lobe

•    Renal pelvis – flat, funnel-shaped tube lateral to the hilus within the renal sinus

•      Major calyces – large branches of the renal pelvis

•    Collect urine draining from papillae

•    Empty urine into the pelvis

•      Urine flows through the pelvis and ureters to the bladder

Blood and Nerve Supply

•      Approximately one-fourth (1200 ml) of systemic cardiac output flows through the kidneys each minute

•      Arterial flow into and venous flow out of the kidneys follow similar paths

•      The nerve supply is via the renal plexus

The Nephron

•      Nephrons are the blood-processing units that form urine, consisting of:

•    Glomerulus – a tuft of capillaries associated with a renal tubule

•    Glomerular (Bowman’s) capsule – blind, cup-shaped end of a renal tubule that completely surrounds the glomerulus

•    Renal corpuscle – the glomerulus and its Bowman’s capsule

•    Glomerular endothelium – fenestrated epithelium that allows solute-rich, virtually protein-free filtrate to pass from the blood into the glomerular capsule

Anatomy of the Glomerular Capsule

•      The external parietal layer is a structural layer

•      The visceral layer consists of modified, branching, epithelial podocytes

•      Extensions of the octopus-like podocytes terminate in foot processes

•      Filtration slits – openings between the foot processes that allow filtrate to pass into the capsular space

Renal tubule

•      Proximal convoluted tubule (PCT) – composed of cuboidal cells with numerous microvilli and mitochondria

•    Resorbs water and solutes from filtrate and secretes substances into it

•      Loop of Henle – a hairpin-shaped loop of the renal tubule

•    Proximal part is similar to the proximal convoluted tubule

•    Proximal part is followed by the thin segment (simple squamous cells) and the thick segment (cuboidal to columnar cells)

•      Distal convoluted tubule (DCT) – cuboidal cells without microvilli that function more in secretion that reabsorption

Connecting Tubules

•      The distal portion of the distal convoluted tubule nearer to the collecting ducts

•      Two important cell types are found here

•    Intercalated cells

•   Cuboidal cells with microvilli

•   Function in maintaining the acid-base balance of the body

•    Principal cells

•   Cuboidal cells without microvilli

•   Help maintain the body’s water and salt balance

Nephrons

•      Cortical nephrons – 85% of nephrons; located in the cortex

•      Juxtamedullary nephrons:

•    Are located at the cortex-medulla junction

•    Have loops of Henle that deeply invade the medulla

•    Have extensive thin segments

•    Are involved in the production of concentrated urine

Capillary Beds of the Nephron

•      Every nephron has two capillary beds

•    Glomerulus

•    Peritubular capillaries

•      Each glomerulus is:

•    Fed by an afferent arteriole

•    Drained by an efferent arteriole

•      Blood pressure in the glomerulus is high because:

•    Arterioles are high-resistance vessels

•    Afferent arterioles have larger diameters than efferent arterioles

•      Fluids and solutes are forced out of the blood throughout the entire length of the glomerulus

Capillary Beds

•      Peritubular beds are low-pressure, porous capillaries adapted for absorption that:

•    Arise from efferent arterioles

•    Cling to adjacent renal tubules

•    Empty into the renal venous system

•      Vasa recta – long, straight efferent arterioles of juxamedullary nephrons

Vascular Resistance in Microcirculation

•      Afferent and efferent arterioles offer high resistance to blood flow

•      Blood pressure declines from 95mm Hg in renal arteries to 8 mm Hg in renal veins

•      Resistance in afferent arterioles:

•    Protects glomeruli from fluctuations in systemic blood pressure

•      Resistance in efferent arterioles:

•    Reinforces high glomerular pressure

•    Reduces hydrostatic pressure in peritubular capillaries

Juxtablomerular Apparatus (JGA)

•      Where the distal tubule lies against the afferent (sometimes efferent) arteriole

•      Arteriole walls have juxtaglomerular (JG) cells

•    Enlarged, smooth muscle cells

•    Have secretory granules containing renin

•    Act as mechanoreceptors

•      Macula densa

•    Tall, closely packed distal tubule cells

•    Lie adjacent to JG cells

•    Function as chemoreceptors or osmoreceptors

•      Mesanglial cells appear to control the glomerular filtration rate

Filtration Membrane

•      Filter that lies between the blood and the interior of the glomerular capsule

•      It is composed of three layers

•    Fenestrated endothelium of the glomerular capillaries

•    Visceral membrane of the glomerular capsule (podocytes)

•    Basement membrane composed of fused basal laminas of the other layers

Mechanism of Urine Formation

•      The kidneys filter the body’s entire plasma volume 60 times each day

•      The filtrate:

•    Contains all plasma components except protein

•    Loses water, nutrients, and essential ions to become urine

•      The urine contains metabolic wastes and unneeded substances

•      Urine formation and adjustment of blood composition involves three major processes

•    Glomerular filtration

•    Tubular reabsorption

•    Secretion

Glomerular Filtration

•      Principles of fluid dynamics that account for tissue fluid in all capillary beds apply to the glomerulus as well

•      The glomerulus is more efficient than other capillary beds because:

•    Its filtration membrane is significantly more permeable

•    Glomerular blood pressure is higher

•    It has a higher net filtration pressure

•      Plasma proteins are not filtered and are used to maintain oncotic pressure of the blood

Net Filtration Pressure (NFP)

•      The pressure responsible for filtrate formation

•      NFP equals the glomerular hydrostatic pressure (HPg) minus the oncotic pressure of glomerular blood (OPg) combined with the capsular hydrostatic pressure (HPc)

 

NFP = HPg – (OPg + HPc)

Glomerular Filtration Rate (GFR)

•      The total amount of filtrate formed per minute by the kidneys

•      Factors governing filtration rate at the capillary bed are:

•    Total surface area available for filtration

•    Filtration membrane permeability

•    Net filtration pressure

•      GFR is directly proportional to the NFP

•      Changes in GFR normally result from changes in glomerular blood pressure

Regulation of Glomerular Filtration

•      If the GFR is too high:

•    Needed substances cannot be reabsorbed quickly enough and are lost in the urine

•      If the GFR is too low:

•    Everything is reabsorbed, including wastes that are normally disposed of

•      Three mechanisms control the GFR 

•    Renal autoregulation (intrinsic system)

•    Neural controls

•    The renin-angiotensin system (hormonal mechanism)

Intrinsic Controls

•      Under normal conditions, renal autoregulation maintains a nearly constant glomerular filtration rate

•      Autoregulation entails two types of control

•    Myogenic – responds to changes in pressure in the renal blood vessels

•    Tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus

Sympathetic Nervous System (SNS) Controls

•      When the SNS is at rest:

•    Renal blood vessels are maximally dilated

•    Autoregulation mechanisms prevail

•      Under stress:

•    Norepinephrine is released by the SNS

•    Epinephrine is released by the adrenal medulla

•    Afferent arterioles constrict and filtration is inhibited 

•      The SNS also stimulates the renin-angiotensin mechanism

Renin-Angiotensin Mechanism

•      Is triggered when the JG cells release renin

•      Renin acts on angiotensinogen to release angiotensin I 

•      Angiotensin I is converted to angiotensin II

•      Angiotensin II:

•    Causes mean arterial pressure to rise

•    Stimulates the adrenal cortex to release aldosterone

•      As a result, both systemic and glomerular hydrostatic pressure rise

Renin Release

•      Renin release is triggered by:

•    Reduced stretch of the granular JG cells

•    Stimulation of the JG cells by activated macula densa cells

•    Direct stimulation of the JG cells via b1-adrenergic receptors by renal nerves

•    Angiotensin II

Other Factors Affecting Glomerular Filtration

•      Prostaglandins (PGE2 and PGI2)

•    Vasodilators produced in response to sympathetic stimulation and angiotensin II

•    Are thought to prevent renal damage when peripheral resistance is increased

•      Nitric oxide – vasodilator produced by the vascular endothelium

•      Adenosine – vasoconstrictor on renal vasculature

•      Endothelin – a powerful vasoconstrictor secreted by tubule cells

Tubular Reabsorption

•      A transepithelial process whereby most tubule contents are returned to the blood

•      Transported substances move through three membranes 

•    Luminal and basolateral membranes of tubule cells

•    Endothelium of peritubular capillaries

•      Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways

•      All organic nutrients are reabsorbed

•      Water and ion reabsorption is hormonally controlled

•      Reabsorption may be an active (requires ATP) or passive process

Sodium Reabsorption: Primary Active Transport

•      Sodium reabsorption is almost always by active transport

•    Na+ enters the tubule cells at the luminal membrane

•    Is actively transported out of the tubules by a Na+-K+ ATPase pump

•      From there it moves to peritubular capillaries due to:

•    Low hydrostatic pressure

•    High osmotic pressure of the blood

•      Na+ reabsorption provides the energy and the means for reabsorbing most other solutes

Reabsorption by PCT Cells

•      Active pumping of Na+ drives reabsorption of:

•    Water by osmosis

•    Anions and fat-soluble substance by diffusion

•    Organic nutrients and selected cations by secondary active transport

Nonreabsorbed Substances

•      A transport maximum (Tm):

•    Reflects the number of carriers in the renal tubules available

•    Exists for nearly every substance that is actively reabsorbed

•      When the carriers are saturated, excess of that substance is excreted

•      Substances are not reabsorbed if they:

•    Lack carriers

•    Are not lipid soluble

•    Are too large to pass through membrane pores

•      Urea, creatinine, and uric acid are the most important nonreabsorbed substances

Absorptive Capabilities of Renal Tubules and Collecting Ducts

•      Substances reabsorbed in PCT include:

•    Sodium, all nutrients, cations, anions, and water

•    Urea and lipid-soluble solutes

•    Small proteins

•      Loop of Henle

•    H2O, Na+, Cl-, K+ (descending)

•    Ca2+, Mg2+, and Na+ (ascending)

•      DCT

•    Ca2+, Na+, H+, K+, and water

•    HCO3- and Cl-

•      Collecting duct

•    Water and urea

Na+ Entry into Tubule Cells

•      Passive entry: Na+-K+ ATPase pump

•      In the PCT: facilitated diffusion using symport and antiport carriers

•      In the ascending loop of Henle: facilitated diffusion via Na+-K+-2Cl- symport system

•      In the DCT: Na+-Cl– symporter

•      In collecting tubules: diffusion through membrane pores

Tubular Secretion

•      Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate

•      Tubular secretion is important for:

•    Disposing of substances not already in the filtrate

•    Eliminating undesirable substances such as urea and uric acid

•    Ridding the body of excess potassium ions

•    Controlling blood pH

Regulation of Urine Concentration and Volume

•      Osmolality

•    The number of solute particles dissolved in 1L of water

•    Reflects the solution’s ability to cause osmosis

•      Body fluids are measured in milliosmols (mOsm)

•      The kidneys keep the solute load of body fluids constant at about 300 mOsm

•      This is accomplished by the countercurrent mechanism

Countercurrent Mechanism

•      By the time the filtrate reaches the loop of Henle, the amount and flow are reduced by 65% but it is still isosmotic

•      The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm

•      The loop of Henle functions as a countercurrent multiplier

•      Dissipation of the medullary osmotic gradient is prevented because the blood in the vasa recta equilibrates with the interstitial fluid

Loop of Henle: Countercurrent Multiplier

•      The descending loop of Henle:

•    Is relatively impermeable to solutes

•    Is permeable to water

•      The ascending loop of Henle:

•    Is impermeable to water

•    Actively transports sodium chloride into the surrounding interstitial fluid

•      Collecting ducts in the deep medullary regions are permeable to urea

•      The vasa recta is a countercurrent exchanger that:

•    Maintains the osmotic gradient

•    Delivers nutrient blood supply to the cells in the area

Formation of Dilute Urine

•      Filtrate is diluted in the ascending loop of Henle

•      Dilute urine is created by allowing this filtrate to continue into the renal pelvis

•      This will happen as long as antidiuretic hormone (ADH) is not being secreted

•      Collecting ducts remain impermeable to water; no further water reabsorption occurs

•      Sodium and selected ions can be removed by active and passive mechanisms

•      Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Formation of Concentrated Urine

•      Antidiuretic hormone (ADH) inhibits diuresis

•      This equalizes the osmolality of the filtrate and the interstitial fluid

•      In the presence of ADH, 99% of the water in filtrate is reabsorbed

•      ADH-dependent water reabsorption is called facultative water reabsorption

•      ADH is the signal to produce concentrated urine

•      The kidneys ability to respond depends upon the high medullary osmotic gradient

Diuretics

•      Chemicals that enhance the urinary output include:

•    Any substance not reabsorbed

•    Substances that exceed the ability of the renal tubules to reabsorb it

•      Osmotic diuretics include:

•    High glucose levels – carries water out with the glucose

•    Alcohol – inhibits the release of ADH

•    Caffeine and most diuretic drugs – inhibit sodium ion reabsorption

•    Lasix – inhibits Na+-K+-2Cl- symporters

Renal Clearance

•      The volume of plasma that is cleared of a particular substance in a given time

•      Renal clearance tests are used to:

•    Determine the GFR

•    Detect glomerular damage

•    Follow the progress of diagnosed renal disease

RC = UV/P

RC = renal clearance rate

U = concentration (mg/ml) of the substance in urine

V = flow rate of urine formation (ml/min)

P = concentration of the same substance in plasma

Physical Characteristics of Urine

•      Color and transparency

•    Clear, pale to deep yellow (due to urochrome)

•    Concentrated urine has a deeper yellow color

•    Drugs, vitamin supplements, and diet can change the color of urine

•    Cloudy urine may indicate infection of the urinary tract

•      Odor

•    Fresh urine is slightly aromatic

•    Standing urine develops an ammonia odor

•    Some drugs and vegetables (asparagus) alter the usual odor

•      pH

•    Slightly acidic (pH 6) with a range of 4.5 to 8.0

•    Diet can alter pH

•      Specific gravity

•    Ranges from 1.001 to 1.035

•    Is dependent on solute concentration

Chemical Characteristics of Urine

•      Urine is 95% water and 5% solutes

•      Nitrogenous wastes include urea, uric acid, and creatinine

•      Other normal solutes include:

•    Sodium, potassium, phosphate, and sulfate ions

•    Calcium, magnesium, and bicarbonate ions

•      Abnormally high concentrations of any urinary constituents may indicate pathology

•      Disease states alter urine composition dramatically

Ureters

•      Slender tubes that convey urine from the kidneys to the bladder

•      Ureters enter the base of  the bladder through the posterior wall

•    This closes their distal ends as bladder pressure increases and prevents backflow of urine into the ureters

•      Ureters have a trilayered wall 

•    Transitional epithelial mucosa

•    Smooth muscle mucosa

•    Fibrous connective tissue adventitia

•      Ureters actively propel urine to the bladder via response to smooth muscle stretch

Urinary Bladder

•      Smooth, collapsible, muscular sac that temporarily stores urine

•      It lies retroperitoneally on the pelvic floor posterior to the pubic symphysis

•    Males – prostate gland surrounds the neck inferiorly

•    Females – anterior to the vagina and uterus

•      Trigone – triangular area outlined by the openings for the ureters and the urethra

•    Clinically important because infections tend to persist in this region

•      The bladder wall has three layers 

•    Transitional epithelial mucosa

•    A thick muscular layer

•    A fibrous adventitia

•      The bladder is distensible and collapses when empty

•      As urine accumulates, the bladder expands without significant rise in internal pressure

Urethra

•      Muscular tube that:

•    Drains urine from the bladder

•    Conveys it out of the body

•      Sphincters keep the urethra closed when urine is not being passed

•    Internal urethral sphincter – involuntary sphincter at the bladder-urethra junction

•    External urethral sphincter – voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm

•    Levator ani muscle – voluntary urethral sphincter

•      The female urethra is tightly bound to the anterior vaginal wall

•      Its external opening lies anterior to the vaginal opening and posterior to the clitoris

•      The male urethra has three named regions

•    Prostatic urethra – runs within the prostate gland

•    Membranous urethra – runs through the urogenital diaphragm

•    Spongy (penile) urethra – passes through the penis and opens via the external urethral orifice

Micturition (Voiding or Urination)

•      The act of emptying the bladder

•      Distension of bladder walls initiates spinal reflexes that:

•    Stimulate contraction of the external urethral sphincter

•    Inhibit the detrusor muscle and internal sphincter (temporarily)

•      Voiding reflexes:

•    Stimulate the detrusor muscle to contract

•    Inhibit the internal and external sphincters

Developmental Aspects

•      Three sets of embryonic kidneys develop, with only the last set persisting

•      The pronephros never functions but its pronephric duct persists and connects to the cloaca

•      The mesonephros claims this duct and it becomes the mesonephric duct

•      The final metanephros develop by the fifth week and develop into adult kidneys

Developmental Aspects

•      Metanephros develop as ureteric buds that incline mesoderm to form nephrons

•      Distal ends of ureteric tubes form the renal pelves, calyces, and collecting ducts

•      Proximal ends called ureteric ducts become the ureters

•      Metanephric kidneys are excreting urine by the third month

•      The cloaca eventually develops into the rectum and anal canal

•      Infants have small bladders and the kidneys cannot concentrate urine, resulting in frequent micturition

•      Control of the voluntary urethral sphincter develops with the nervous system

•      E. coli bacteria account for 80% of all urinary tract infections

•      Sexually transmitted diseases can also inflame the urinary tract

•      Kidney function declines with age, with many elderly becoming incontinent