Chapter 26

The Urinary System

 

Lecture Outline

INTRODUCTION

•      The urinary system consists of two kidneys, two ureters, one urinary bladder, and one urethra (Figure 26.1).

•      Urine is excreted from each kidney through its ureter and is stored in the urinary bladder until it is expelled from the body through the urethra.

•      The specialized branch of medicine that deals with structure, function, and diseases of the male and female urinary systems and the male reproductive system is known as nephrology. The branch of surgery related to male and female urinary systems and the male reproductive system is called urology.

Chapter 26
The Urinary System

•      Kidneys, ureters, urinary bladder & urethra

•      Urine flows from each kidney, down its ureter to the bladder and to the outside via the urethra

•      Filter the blood and return most of water and solutes to the bloodstream

Overview of Kidney Functions

•      Regulation of blood ionic composition

–   Na+, K+, Ca+2, Cl- and phosphate ions

•      Regulation of blood pH, osmolarity & glucose

•      Regulation of blood volume

–   conserving or eliminating water

•      Regulation of blood pressure

–   secreting the enzyme renin

–   adjusting renal resistance

•      Release of erythropoietin & calcitriol

•      Excretion of wastes & foreign substances

 

ANATOMY AND HISTOLOGY OF THE KIDNEYS

•      The paired kidneys are retroperitoneal organs (Figure 26.2).

External Anatomy of the Kidney

•      Near the center of the concave medial border of the kidney is a vertical fissure called the hilus, through which the ureter leaves and blood vessels, lymphatic vessels, and nerves enter and exit (Figure 26.3).

•      Three layers of tissue surround each kidney: the innermost renal capsule, the adipose capsule, and the outer renal fascia.

•      Nephroptosis is an inferior displacement of the kidneys.  It most often occurs in thin people.  This condition is dangerous because the ureters may kink and block urine flow (Clinical Application).

External Anatomy of Kidney

•       Paired kidney-bean-shaped organ

•       4-5 in long, 2-3 in wide,
1 in thick

•       Found just above the waist between the peritoneum & posterior wall of abdomen

–    retroperitoneal (along with adrenal glands & ureters)

•       Protected by 11th & 12th ribs with right kidney lower

 

External Anatomy of Kidney

•       Blood vessels & ureter enter hilus of kidney

•       Renal capsule = transparent membrane maintains organ shape

•       Adipose capsule that helps protect from trauma

•       Renal fascia = dense, irregular connective tissue that holds against back body wall

External Anatomy of Kidney

Internal Anatomy of the Kidney

•      Internally, the kidneys consist of cortex, medulla, pyramids, papillae, columns, calyces, and pelves (Figure 26.3).

•      The renal cortex and renal pyramids constitute the functional portion or parenchyma of the kidney.

•      The nephron is the functional unit of the kidney.

Internal Anatomy of the Kidneys

•      Parenchyma of kidney

–   renal cortex = superficial layer of kidney

–   renal medulla

•   inner portion consisting of 8-18 cone-shaped renal pyramids separated by renal columns

•   renal papilla point toward center of kidney

•      Drainage system fills renal sinus cavity

–   cuplike structure (minor calyces) collect urine from the papillary ducts of the papilla

–   minor & major calyces empty into the renal pelvis which empties into the ureter

Internal Anatomy of Kidney

•       What is the difference between renal hilus & renal sinus?

•       Outline a major calyx & the border between cortex & medulla.

Blood and Nerve Supply of the Kidneys

•      Blood enters the kidney through the renal artery and exits via the renal vein.

–   Figures 26.4 and 26.5 show the branching pattern of renal blood vessels and the path of blood flow through the kidneys.

 

•      In a kidney transplant a donor kidney is placed in the pelvis of the recipient through an abdominal incision.  The renal artery, renal vein, and ureter of the donor kidney are connected to the corresponding structure in the recipient.  The patient is then placed on immunosuppressive drugs to prevent rejection of the transplanted kidney.

Blood & Nerve Supply of Kidney

•      Abundantly supplied with blood vessels

–   receive 25% of resting cardiac output via renal arteries

•      Functions of different capillary beds

–   glomerular capillaries where filtration of blood occurs

•   vasoconstriction & vasodilation of afferent & efferent arterioles produce large changes in renal filtration

–   peritubular capillaries that carry away reabsorbed substances from filtrate

–   vasa recta supplies nutrients to medulla without disrupting its osmolarity form

•      The nerve supply to the kidney is derived from the renal plexus (sympathetic division of ANS).  Sympathetic vasomotor nerves regulate blood flow & renal resistance by altering arterioles

 

 

Nephrons

•      A nephron consists of a renal corpuscle where fluid is filtered, and a renal tubule into which the filtered fluid passes (Figure 26.5).

•      Nephrons perform three basic functions: glomerular filtration, tubular reabsorption, and tubular secretion.

•      A renal tubule consists of a proximal convoluted tubule (PCT), loop of Henle (nephron loop), and distal convoluted tubule (DCT).

•      Distal convoluted tubules of several nephrons drain into to a single collecting duct and many collecting ducts drain into a small number of papillary ducts.

Blood Vessels around the Nephron

•      Glomerular capillaries are formed between the afferent & efferent arterioles

•      Efferent arterioles give rise to the peritubular capillaries and vasa recta

Nephrons

•      The loop of Henle consists of a descending limb, a thin ascending limb, and a thick ascending limb (Figure 26.5).

•      There are two types of nephrons that have differing structure and function.

–   A cortical nephron usually has its glomerulus in the outer portion of the cortex and a short loop of Henle that penetrates only into the outer region of the medulla (Figure 26.5a).

–   A juxtamedullary nephron usually has its glomerulus deep in the cortex close to the medulla; its long loop of Henle stretches through the medulla and almost reaches the renal papilla (Figure 26.5b).

Blood Supply to the Nephron

The Nephron

•      Kidney has over 1 million nephrons composed of a corpuscle and tubule

•      Renal corpuscle = site of plasma filtration

–   glomerulus is capillaries where filtration occurs

–   glomerular (Bowman’s) capsule is double-walled epithelial cup that collects filtrate

•      Renal tubule

–   proximal convoluted tubule

–   loop of Henle dips down into medulla

–   distal convoluted tubule

•      Collecting ducts and papillary ducts drain urine to the renal pelvis and ureter.

Cortical Nephron

•       80-85% of nephrons are cortical nephrons

•       Renal corpuscles are in outer cortex and loops of Henle lie mainly in cortex

Juxtamedullary Nephron

•       15-20% of nephrons are juxtamedullary nephrons

•       Renal corpuscles close to medulla and long loops of Henle extend into deepest medulla enabling excretion of dilute or concentrated urine

Histology of the Nephron and Collecting Duct

•      Glomerular Capsule

–   The glomerular capsule consists of visceral and parietal layers (Figure 26.6).

–   The visceral layer consists of modified simple squamous epithelial cells called podocytes.

–   The parietal layer consists of simple squamous epithelium and forms the outer wall of the capsule.

•      Fluid filtered from the glomerular capillaries enters the capsular space, the space between the two layers of the glomerular capsule.

Histology of the Nephron & Collecting Duct

•      Single layer of epithelial cells forms walls of entire tube

•      Distinctive features due to function of each region

–   microvilli

–   cuboidal versus simple

–   hormone receptors

Renal Tubule and Collecting Duct

•      Table 26.1 illustrates the histology of the cells that form the renal tubule and collecting duct.

•      The juxtaglomerular apparatus (JGA) consists of the juxtaglomerular cells of an afferent arteriole and the macula densa. The JGA helps regulate blood pressure and the rate of blood filtration by the kidneys (Figure 26.6).

•      Most of the cells of the distal convoluted tubule are principal cells that have receptors for ADH and aldosterone. A smaller number are intercalated cells which play a role in the homeostasis of blood pH.

•      The number of nephrons is constant from birth. They may increase in size, but not in number (Clinical Application).

Structure of Renal Corpuscle

•       Bowman’s capsule surrounds capsular space

–   podocytes cover capillaries to form visceral layer

–   simple squamous cells form parietal layer of capsule

•       Glomerular capillaries arise from afferent arteriole & form a ball before emptying into efferent arteriole

 

Histology of Renal Tubule & Collecting Duct

•       Proximal convoluted tubule

–    simple cuboidal with brush border of microvilli that increase surface area

•       Descending limb of loop of Henle

–    simple squamous

•       Ascending limb of loop of Henle

–    simple cuboidal to low columnar

–    forms juxtaglomerular apparatus where makes contact with afferent arteriole

•    macula densa is special part of ascending limb

•       Distal convoluted & collecting ducts

–    simple cuboidal composed of principal & intercalated cells which have microvilli

 

 

 

Juxtaglomerular Apparatus

•       Structure where afferent arteriole makes contact with ascending limb of loop of Henle

–    macula densa is thickened part of ascending limb

–    juxtaglomerular cells are modified muscle cells in arteriole

Number of Nephrons

•      Remains constant from birth

–   any increase in size of kidney is size increase of individual nephrons

•      If injured, no replacement occurs

•      Dysfunction is not evident until function declines by 25% of normal (other nephrons handle the extra work)

•      Removal of one kidney causes enlargement of the remaining until it can filter at 80% of normal rate of 2 kidneys

OVERVIEW OF RENAL PHYSIOLOGY

•      Nephrons and collecting ducts perform three basic processes while producing urine: glomerular filtration, tubular secretion, and tubular reabsorption (Figure 26.7).

 

Overview of Renal Physiology

•      Nephrons and collecting ducts perform 3 basic processes

–   glomerular filtration

•   a portion of the blood plasma is filtered into the kidney

–   tubular reabsorption

•   water & useful substances are reabsorbed into the blood

–   tubular secretion

•   wastes are removed from the blood & secreted into urine

•      Rate of excretion of any substance is its rate of filtration, plus its rate of secretion, minus its rate of reabsorption

Overview of Renal Physiology

•      Glomerular filtration of plasma

•      Tubular reabsorption

•      Tubular secretion

GLOMERULAR FILTRATION

•      The fluid that enters the capsular space is termed glomerular filtrate.

•      The fraction of plasma in the afferent arterioles of the kidneys that becomes filtrate is termed the filtration fraction.

 

Glomerular Filtration

•      Blood pressure produces glomerular filtrate

•      Filtration fraction is 20% of plasma

•      48 Gallons/day
filtrate reabsorbed
to 1-2 qt. urine

•      Filtering capacity
enhanced by:

–   thinness of membrane

    & large surface area of

    glomerular capillaries

–   glomerular capillary BP is high due to small size of efferent arteriole

The Filtration Membrane

•      The filtering unit of a nephron is the endothelial-capsular membrane.

–   glomerular endothelium

–   glomerular basement membrane

–   slit membranes between pedicels of podocytes.

•      Filtered substances move from the blood stream through three barriers: a glomerular endothelial cell, the basal lamina, and a filtration slit formed by a podocyte (Figure 26.8).

•      The principle of filtration - to force fluids and solutes through a membrane by pressure - is the same in glomerular capillaries as in capillaries elsewhere in the body.

Filtration Membrane

•      #1 Stops all cells and platelets

•      #2 Stops large plasma proteins

•      #3 Stops medium-sized proteins, not small ones

Net Filtration Pressure

•      NFP = total pressure that promotes filtration

•      NFP = GBHP - (CHP + BCOP) = 10mm Hg

Net Filtration Pressure

•      Glomerular filtration depends on three main pressures, one that promotes and two that oppose filtration (Figure 26.9).

•      Filtration of blood is promoted by glomerular blood hydrostatic pressure (BGHP) and opposed by capsular hydrostatic pressure (CHP) and blood colloid osmotic pressure (BCOP). 

–   The net filtration pressure (NFP) is about 10 mm Hg.

•      In some kidney diseases, damaged glomerular capillaries become so permeable that plasma proteins enter the filtrate, causing an increase in NFP and GFR and a decrease in BCOP. (Clinical Application)

Glomerular Filtration Rate

•      Amount of filtrate formed in all renal corpuscles of both kidneys / minute

–   average adult male rate is 125 mL/min

•      Homeostasis requires GFR that is constant

–   too high & useful substances are lost due to the speed of fluid passage through nephron

–   too low and sufficient waste products may not be removed from the body

•      Changes in net filtration pressure affects GFR

–   filtration stops if GBHP drops to 45mm Hg

–   functions normally with mean arterial pressures 80-180

Regulation of GFR

•      The mechanisms that regulate GFR adjust blood flow into and out of the glomerulus and alter the glomerular capillary surface area available for filtration.

•      The three principal mechanisms that control GFR are renal autoregulation, neural regulation, and hormonal regulation.

Regulation of GFR

Renal Autoregulation of GFR

•      Mechanisms that maintain a constant GFR despite changes in arterial BP

–   myogenic mechanism

•   systemic increases in BP, stretch the afferent arteriole

•   smooth muscle contraction reduces the diameter of the arteriole returning the GFR to its previous level in seconds

–   tubuloglomerular feedback

•   elevated systemic BP raises the GFR so that fluid flows too rapidly through the renal tubule & Na+, Cl- and water are not reabsorbed

•   macula densa detects that difference & releases a vasoconstrictor from the juxtaglomerular apparatus

•   afferent arterioles constrict & reduce GFR

Neural Regulation of GFR

•       Blood vessels of the kidney are supplied by sympathetic fibers that cause vasoconstriction of afferent arterioles

•       At rest, renal BV are maximally dilated because sympathetic activity is minimal

–    renal autoregulation prevails

•       With moderate sympathetic stimulation, both afferent & efferent arterioles constrict equally

–    decreasing GFR equally

•       With extreme sympathetic stimulation (exercise or hemorrhage), vasoconstriction of afferent arterioles reduces GFR

–    lowers urine output & permits blood flow to other tissues

Hormonal Regulation of GFR

•      Atrial natriuretic peptide (ANP) increases GFR

–   stretching of the atria that occurs with an increase in blood volume causes hormonal release

•   relaxes glomerular mesangial cells increasing capillary surface area and increasing GFR

•      Angiotensin II reduces GFR

–   potent vasoconstrictor that narrows both afferent & efferent arterioles reducing GFR

TUBULAR REABSORPTION AND TUBULAR SECRETION

Tubular Reabsorption & Secretion

•       Normal GFR is so high that volume of filtrate in capsular space in half an hour is greater than the total plasma volume

•       Nephron must reabsorb 99% of the filtrate

–    PCT with their microvilli do most of work with rest of nephron doing just the fine-tuning

•    solutes reabsorbed by active & passive processes

•    water follows by osmosis

•    small proteins by pinocytosis

•       Important function of nephron is tubular secretion

–    transfer of materials from blood into tubular fluid

•    helps control blood pH because of secretion of H+

•    helps eliminate certain substances (NH4+, creatinine, K+)

 

•       Table 26.3 compares the amounts of substances that are filtered, reabsorbed, and excreted in urine with the amounts present in blood plasma.

 

Reabsorption Routes

•      A substance being reabsorbed can move between adjacent tubule cells or through an individual tubule cell before entering a peritubular capillary (Figure 26.11).

•      Fluid leakage between cells is known as paracellular reabsorption.

•      In transcellular reabsorption, a substance passes from the fluid in the tubule lumen through the apical membrane of a tubule cell, across the cytosol, and out into interstitial fluid through the basolateral membrane.

Reabsorption Routes

•      Paracellular reabsorption

–   50% of reabsorbed material
moves between cells by
diffusion in some parts of
tubule

•      Transcellular reabsorption

–   material moves through
both the apical and basal
membranes of the tubule
cell by active transport

Transport Mechanisms

•      Solute reabsorption drives water reabsorption. The mechanisms that accomplish Na⁺ reabsorption in each portion of the renal tubule and collecting duct recover not only filtered Na⁺ but also other electrolytes, nutrients, and water.

Transport Mechanisms

•      Apical and basolateral membranes of tubule cells have different types of transport proteins

•      Reabsorption of Na+ is important

–   several transport systems exist to reabsorb Na+

–   Na+/K+ ATPase pumps sodium from tubule cell cytosol through the basolateral membrane only

•      Water is only reabsorbed by osmosis

–   obligatory water reabsorption occurs when water is “obliged” to follow the solutes being reabsorbed

–   facultative water reabsorption occurs in collecting duct under the control of antidiuretic hormone

 

Active and Passive Transport Processes

•      Transport across membranes can be either active or passive (See Chapter 3).

•      In primary active transport the energy derived from ATP is used to “pump” a substance across a membrane.

•      In secondary active transport the energy stored in an ion’s electrochemical gradient drives another substance across the membrane.

Transport Maximum (T_m)

•      Each type of symporter has an upper limit on how fast it can work, called the transport maximum (T_m).

•      The mechanism for water reabsorption by the renal tubule and collecting duct is osmosis.

•      About 90% of the filtered water reabsorbed by the kidneys occurs together with the reabsorption of solutes such as Na⁺, Cl^-, and glucose.

•      Water reabsorption together with solutes in tubular fluid is called obligatory water reabsorption.

•      Reabsorption of the final water, facultative reabsorption, is based on need and occurs in the collecting ducts and is regulated by ADH.

Glucosuria

•      Renal symporters can not reabsorb glucose fast enough if blood glucose level is above 200 mg/mL

–   some glucose remains in the urine (glucosuria)

•      Common cause is diabetes mellitis because insulin activity is deficient and blood sugar is too high

•      Rare genetic disorder produces defect in symporter that reduces its effectiveness

 

 

Reabsorption and Secretion in the Proximal Convoluted Tubule

Reabsorption in the Proximal Convoluted Tubule

•      The majority of solute and water reabsorption from filtered fluid occurs in the proximal convoluted tubules and most absorptive processes involve Na⁺.

•      Proximal convoluted tubule Na⁺ transporters promote reabsorption of 100% of most organic solutes, such as glucose and amino acids; 80-90% of bicarbonate ions; 65% of water, Na⁺, and K⁺; 50% of Cl^-; and a variable amount of Ca⁺², Mg⁺², and HPO₄^-2.

•      Normally, 100% of filtered glucose, amino acids, lactic acid, water-soluble vitamins, and other nutrients are reabsorbed in the first half of the PCT by Na⁺ symporters. Figure 26.12 shows the operation of the main Na⁺-glucose symporters in PCT cells.

Reabsorption in the Proximal Convoluted Tubule

•      Na⁺/H⁺ antiporters achieve Na⁺ reabsorption and return filtered HCO₃^- and water to the peritubular capillaries (Figure 26.13). PCT cells continually produce the H⁺ needed to keep the antiporters running by combining CO₂ with water to produce H₂CO₃ which dissociates into H⁺ and HCO₃^-.

•      Diffusion of Cl^- into interstitial fluid via the paracellular route leaves tubular fluid more positive than interstitial fluid. This electrical potential difference promotes passive paracellular reabsorption of Na⁺, K⁺, Ca⁺², and Mg⁺² (Figure 26.14).

•      Reabsorption of Na⁺ and other solutes creates an osmotic gradient that promotes reabsorption of water by osmosis (Figure 26.15).

Reabsorption in the PCT

•       Na+ symporters help reabsorb  materials from the tubular filtrate

•       Glucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubule

•       Intracellular sodium levels are kept low due to Na+/K+ pump

Reabsorption of Bicarbonate, Na+ & H+ Ions

•       Na+ antiporters reabsorb Na+ and secrete H+

–    PCT cells produce the H+ & release bicarbonate ion to the peritubular capillaries

–    important buffering system

•       For every H+ secreted into the tubular fluid, one filtered bicarbonate eventually returns to the blood

Secretion of NH₃ and NH₄⁺ in the Proximal Convoluted Tubule

•      Urea and ammonia in the blood are both filtered at the glomerulus and secreted by the proximal convoluted tubule cells into the tubules.

•      The deamination of the amino acid glutamine by PCT cells generates both NH₃ and new HCO₃^- (Figure 26.16).

•      At the pH inside tubule cells, most NH₃ quickly binds to H⁺ and becomes NH₄⁺.

•      NH₄⁺ can substitute for H⁺ aboard Na⁺/H⁺ antiporters and be secreted into tubular fluid.

•      Na⁺/HCO₃⁺ symporters provide a route for reabsorbed Na⁺ and newly formed HCO₃^- to enter the bloodstream.

Passive Reabsorption in the 2nd Half of PCT

•       Electrochemical gradients produced by symporters & antiporters causes passive reabsorption of other solutes

•       Cl-, K+, Ca+2, Mg+2 and urea passively diffuse into the peritubular capillaries

•       Promotes osmosis in PCT (especially permeable due to aquaporin-1 channels