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The Urinary System

P A R T A

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Kidney Functions

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

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Other Renal Functions

Gluconeogenesis during prolonged fasting Production of renin to help regulate blood

pressure and erythropoietin to stimulate RBC production

Activation of vitamin D

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Other Urinary System Organs

Urinary bladder – provides a temporary storage reservoir for urine

Paired ureters – transport urine from the kidneys to the bladder

Urethra – transports urine from the bladder out of the body

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Urinary System Organs

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Kidney Location and External Anatomy The kidneys lie in a retroperitoneal position in

the superior lumbar region The right kidney is lower than the left because

it is crowded by the liver The lateral surface is convex; the medial

surface is concave The renal hilus leads to the renal sinus Ureters, renal blood vessels, lymphatics, and

nerves enter and exit at the hilus

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Layers of Tissue Supporting the Kidney Renal capsule – fibrous capsule that surrounds

the kidney Adipose capsule – cushions the kidney and

helps attach it to the body wall Renal fascia – outer layer of dense fibrous

connective tissue that anchors the kidney

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Kidney Location and External Anatomy

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Internal Anatomy (Frontal Section) Cortex – the light colored, outer region Medulla – exhibits cone-shaped medullary

(renal) pyramids separated by columnsThe medullary pyramid and its surrounding

cortex constitute a lobeBaseApex or papilla

Minor calyces- collect the urine from the papilla

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Internal Anatomy

Major calyces Receive the urine from the minor calyces

Renal pelvis Funnel shaped tube that collect urine from

the major calyces Renal sinus Urine flows through the pelvis and ureters to

the bladder

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Internal Anatomy

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Blood and Nerve Supply

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

The nerve supply is via the renal plexus

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Renal Vascular Pathway

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The Nephron

Nephrons are the structural and functional units that form urine, consisting of:Glomerulus – a tuft of capillaries associated

with a renal tubuleGlomerular (Bowman’s) capsule – blind,

cup-shaped end of a renal tubule that completely surrounds the glomerulus

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The Nephron

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

Renal tubules

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The Nephron

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Anatomy of the Glomerular Capsule The external parietal layer is a structural layer The visceral layer consists of modified,

branching epithelial podocytesExtensions 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

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Renal Tubules

Proximal convoluted tubule (PCT) – composed of cuboidal cells with numerous microvilli and mitochondriaReabsorbs water and solutes from filtrate

and secretes substances into it

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Renal Tubules

Loop of Henle – a loop of the renal tubuleProximal part is similar to the proximal

convoluted tubuleProximal 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 than reabsorption

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Renal Tubule

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Renal Tubules

The distal portion of the distal convoluted tubule and the collecting ducts have two types of cells:

Principal Intercalated

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Renal Tubules

Intercalated cellsCuboidal cells with microvilli Function in maintaining the acid-base

balance of the body Principal cells

Cuboidal cells without microvilliHelp maintain the body’s water and salt

balance

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Nephrons

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

Juxtamedullary nephrons:Are located at the cortex-medulla junctionHave loops of Henle that deeply invade the

medulla Have extensive thin segmentsAre involved in the production of

concentrated urine

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Nephron Anatomy

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Capillary Beds of the Nephron

Every nephron has two capillary bedsGlomerulus Peritubular capillaries

Each glomerulus is: Fed by an afferent arteriole Drained by an efferent arteriole

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Capillary Beds of the Nephron

Blood pressure in the glomerulus is high because:Arterioles are high-resistance vesselsAfferent arterioles have larger diameters

than efferent arterioles Fluids and solutes are forced out of the blood

throughout the entire length of the glomerulus

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Capillary Beds

Peritubular beds are low-pressure, porous capillaries adapted for absorption that: Arise from efferent arteriolesCling to adjacent renal tubulesEmpty into the renal venous system

Vasa recta – long, straight capillaries of juxtamedullary nephrons

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Capillary Beds

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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

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Vascular Resistance in Microcirculation Resistance in afferent arterioles:

Protects glomeruli from fluctuations in systemic blood pressure

Resistance in efferent arterioles:Reinforces high glomerular pressureReduces hydrostatic pressure in peritubular

capillaries

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Juxtaglomerular Apparatus (JGA) Juxtaglomerular (granular) cells

Enlarged, smooth muscle cells on the arteriole walls

Secrete renin Macula densa

Tall, closely packed distal tubule cells Lie adjacent to JG cells

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Juxtaglomerular Apparatus (JGA) Main JGA functions:

GFR control Stimulated by high tubular [NaCl]

Renin release Stimulated by low tubular [NaCl]

EPO release

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Juxtaglomerular Apparatus (JGA) When GFR increases:

Macula densa senses the increase of flow and NaCl

Macula densa sends paracrine message to afferent arteriole

Afferent arteriole constricts causing decrease in GFR

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Juxtaglomerular Apparatus (JGA)

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Filtration Membrane

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

It is composed of three layersFenestrated endothelium of the glomerular

capillariesVisceral membrane of the glomerular

capsule (podocytes) A basement membrane

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Filtration Membrane

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Filtration Membrane

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Filtration Barrier

Mesangial cells: Secrete cytokines associated with

immune and inflammatory processes Have filaments that enable them to

contract and decrease capillary blood flow

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Mechanisms of Urine Formation

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

The filtrate:Contains all plasma components except

proteinLoses water, nutrients, and essential ions to

become urine The urine contains metabolic wastes and

unneeded substances

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Mechanisms of Urine Formation

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

filtration– Tubular

reabsorption– Secretion

The Urinary System

P A R T B

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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 more permeableGlomerular 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

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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)

Colloid osmotic pressure in the capsular space

NFP = HPg – (OPg + HPc)

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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 filtrationFiltration membrane permeabilityNet filtration pressure

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Glomerular Filtration Rate (GFR) GFR is directly proportional to the NFP Changes in GFR normally result from changes

in glomerular blood pressure

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Glomerular Filtration Rate (GFR)

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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

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Regulation of Glomerular Filtration Three mechanisms control the GFR

Renal autoregulationNeural controlsHormonal mechanism

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Renal Autoregulation

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

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Renal Autoregulation

Two types of controlMyogenic – increased systemic blood

pressure stimulates stretch receptors on the afferent arterioles that causes its vasoconstriction Important in protecting the kidney from

hypertension-induced glomerular injury

Renal Autoregulation

Flow-dependent tubuloglomerular feedback –increased amount of NaCl in the DCT is sensed by the macula densa. It then releases paracrine signals that

cause afferent vasoconstriction If the NaCl in the DCT is reduced the

paracrines signals will cause afferent vasodilation

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Sympathetic Nervous System

When the sympathetic nervous system is at rest:Renal blood vessels are maximally dilatedAutoregulation mechanisms prevail

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Sympathetic Nervous System

Sympathetic system – when under severe and acute conditions:Norepinephrine and epinephrine cause

vasoconstriction of the afferent arterioles GFR will then decrease

The sympathetic nervous system also stimulates renin release

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Sympathetic Nervous System Renin-angiotensin mechanism Is triggered when the JG cells release renin Renin converts angiotensinogen into

angiotensin I that is converted to angiotensin II As a result systemic pressure rises

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Hormonal Control

Renin release is triggered by:Decreased NaCl concentration at the

macula densaDirect stimulation of the JG cells via 1-

adrenergic receptors by renal nervesDecreased blood pressure at the glomerulus

Hormonal Control

Angiotensin II will Causes direct vasoconstriction of the

efferent arteriole increases GFRStimulates reabsorption of Na

Directly and through aldosteroneStimulates thirst center in the hypothalamusStimulates hypothalamic release of ADH

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Hormonal Control

Causes general vasoconstriction Mean arterial pressure rises

Stimulates the adrenal cortex to release aldosterone

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Extrinsic Control - hormonal

Angiotensin II will Causes direct vasoconstrictionStimulates reabsorption of Na

Directly and through aldosteroneStimulates thirst center in the hypothalamusStimulates hypothalamic release of ADH

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Tubular Reabsorption A return of most of the water and solutes

filtered to the blood Mainly at PCT Reabsorption routes

TranscellularLuminal and basolateral membranes of

tubule cellsEndothelium of peritubular capillaries

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Tubular Reabsorption

ParacellularBetween tubular cells

Leaky tight junctions

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Routes of Water and Solute Reabsorption

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Glomerular filtration produces fluid similar to plasma without proteins

The PCT reabsorbs 60-70% of the filtrate produced

Secretion also occurs in the PCT

Reabsorption and secretion at the PCT

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Tubular Reabsorption Tubular cells use active transport to create an

electrochemical gradient Na is the primary driving force for most renal

reabsorptionIt is directly or indirectly involved passive or

active transport of many substances

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Tubular Reabsorption

Active transport of Na from the lumen to the ECF creates an electrochemical gradient Lumen becomes negative then ECFAnions will follow Na out of the lumenWater will follow by osmosis

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Reabsorption by PCT Cells

Sodium-linked secondary active transport causes the absorption of many other substancesGlucose, amino acids, ions, etcSymport /antiportFacilitated diffusion

OsmosisObligatory water absorption

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Sodium Reabsorption

Na+ is transported from the lumen into the tubular cell passively down its electrochemical gradient

Na is actively transported from the tubular cells to the interstitial fluid by a Na+-K+ ATPase pump

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Sodium Reabsorption

From there it moves to peritubular capillaries due to:Low hydrostatic pressureHigh osmotic pressure of the blood

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

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Reabsorption by PCT Cells

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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

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Nonreabsorbed Substances

Substances are not reabsorbed if they: Lack carriersAre not lipid solubleAre too large to pass through membrane

pores Urea, creatinine, and uric acid are the most

important nonreabsorbed substances

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Absorptive Capabilities of Renal Tubules and Collecting Ducts

Substances reabsorbed in PCT include:Sodium, all nutrients, cations, anions, and

waterUrea and lipid-soluble solutesSmall proteins

Loop of Henle reabsorbs:Only H2O in the descending limbOnly electrolytes in the ascending limb

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Absorptive Capabilities of Renal Tubules and Collecting Ducts

DCT absorbs:Electrolytes and water

Collecting duct absorbs:Water and urea

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Na+ Entry into Tubule Cells

Passive entry: symporter Na-K ATPase creates the ionic gradient for

the symporter In the PCT: facilitated diffusion In the ascending loop of Henle: actively In the DCT: Na+-Cl– mainly active. Under

influence of aldosterone In collecting tubules: primarily active transport.

Also under the influence of aldosterone

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Atrial Natriuretic Peptide Activity

ANP reduces blood Na+ which:Decreases blood volumeLowers blood pressure

ANP lowers blood Na+ by:Acting directly on medullary collecting ducts

to inhibit Na+ reabsorptionCounteracting the effects of angiotensin IIIncreasing GFR and reducing water

reabsorption

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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 acidRidding the body of excess potassium ionsControlling blood pH

The Urinary System

P A R T C

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Regulation of Urine Concentration and Volume

OsmolalityThe number of solute particles dissolved in

1L of waterReflects 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

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Countercurrent Mechanism Happens in the medulla Countercurrent multiplier in the loop of Henle

CountercurrentFluid flowing in opposite directions in two

adjacent tubulesMultiplier

Because it multiplies the salinity deep in the medulla

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Countercurrent Mechanism

Countercurrent Exchanger in the vasa rectaBlood make passive exchange with the

surrounding interstitial fluid of the medulla It looses water when flowing into the

medulla It gains water and looses NaCl when

blood flows toward the cortex

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Countercurrent Mechanism

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

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

Vasa recta also delivers blood to the cells in the area

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Osmotic Gradient in the Renal Medulla

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Loop of Henle: Countercurrent Multiplier The descending loop of Henle:

Is relatively impermeable to solutesIs permeable to water

Obligatory water absorption The ascending loop of Henle:

Is permeable to solutesIs impermeable to water

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Loop of Henle: Countercurrent Multiplier Urea also contributes to the medullary

osmolalityThin limbs of Henle absorb ureaDCT is impermeable to urea Collecting ducts in the deep medullary

regions are permeable to urea

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Loop of Henle: Countercurrent Mechanism

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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

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Formation of Dilute Urine

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)

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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

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Formation of Concentrated Urine ADH-dependent water reabsorption is called

facultative water reabsorption ADH works by inserting aquaporins into the

principal cells of the collecting ducts The kidneys’ ability to respond depends upon

the high medullary osmotic gradient

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Formation of Dilute and Concentrated Urine

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Diuretics

Chemicals that enhance the urinary output include:Any substance not reabsorbedSubstances that exceed the ability of the

renal tubules to reabsorb itSubstances that inhibit Na+ reabsorption

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Diuretics

Osmotic diuretics include:High glucose levels – carries water out with

the glucose Alcohol – inhibits the release of ADHCaffeine and most diuretic drugs – inhibit

sodium ion reabsorptionLasix and Diuril – inhibit Na+-associated

symporters

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Summary of Nephron Function

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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 GFRDetect glomerular damageFollow the progress of diagnosed renal

disease

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Renal Clearance

RC = UV/P

RC = renal clearance rateU = concentration (mg/ml) of the substance

in urineV = flow rate of urine formation (ml/min)P = concentration of the same substance in

plasma

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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

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Physical Characteristics of Urine Odor

Fresh urine is slightly aromaticStanding urine develops an ammonia odorSome drugs and vegetables (asparagus)

alter the usual odor

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Physical Characteristics of Urine 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

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Chemical Composition of Urine

Urine is 95% water and 5% solutes Nitrogenous wastes: 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

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Ureters

Slender tubes that convey urine from the kidneys to the bladder

Ureters enter the base of the bladder through the posterior wallThis closes their distal ends as bladder

pressure increases and prevents backflow of urine into the ureters

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Ureters

Ureters have a trilayered wall Transitional epithelial mucosaSmooth muscle muscularisFibrous connective tissue adventitia

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

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Urinary Bladder

Smooth, collapsible, muscular sac that stores urine

It lies retroperitoneally on the pelvic floor posterior to the pubic symphysisMales – prostate gland surrounds the neck

inferiorlyFemales – anterior to the vagina and

uterus Trigone – triangular area outlined by the

openings for the ureters and the urethraClinically important because infections

tend to persist in this region

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Urinary Bladder

The bladder wall has three layers Transitional epithelial mucosaA thick muscular layerA fibrous adventitia

The bladder is distensible and collapses when empty

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

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Urinary Bladder

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Urethra

Muscular tube that:Drains urine from the bladderConveys it out of the body

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Urethra

Sphincters keep the urethra closed when urine is not being passedInternal urethral sphincter – involuntary

sphincter at the bladder-urethra junctionExternal urethral sphincter – voluntary

sphincter surrounding the urethra as it passes through the urogenital diaphragm

Levator ani muscle – serves as a voluntary constrictor of the urethra

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Urethra 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

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Urine – Storage reflex Distension of bladder walls stimulates stretch

receptors Visceral afferent fibers take the stimulus to the

sacral region of the spinal cord Sympathetic stimulation and parasympathetic

inhibitionRelax the detrusor muscleContracts the internal urethral sphincter

Somatic motor stimulation causes contraction of the external urethral sphincter

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Micturition (Voiding or Urination) The act of emptying the bladder: voiding reflexes Stretch receptors in the bladder wall send stimulus

to the sacral portion of the spinal cordSympathetic neurons are inhibitedParasympathetic neuron are stimulated

Stimulate detrusor muscle to contractCauses internal sphincter to relax

Somatic motor neurons are inhibited

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Micturition (Voiding or Urination)

Also inhibit synapses on the sympathetic neurons

The micturition center integrates information from the bladder with information coming from amygdala and cerebral cortex

When it is appropriate to urinate the external sphincter relaxes

Fear prompts urination

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Micturition (Voiding or Urination)

– Also inhibit synapses on the sympathetic neurons• The micturition center integrates information

from the bladder with information coming from amygdala and cerebral cortex

• When it is appropriate to urinate the external sphincter relaxes

• Fear prompts urination

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Developmental Aspects 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