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Overview of kidney functions 

Chapter 26: The Urinary System

      

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)

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Anatomy and histology of the kidneys 

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Organs of the urinary system in a female

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

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Position and coverings of the kidneys

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Internal anatomy 

Renal cortex – superficial   



Renal medulla – inner region 



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Outer cortical zone Inner juxtamedullary zone Renal columns – portions of cortex that extend between renal pyramids 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

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Anatomy of the kidneys 

Parenchyma (functional portion) of kidney 

 

Internal anatomy of the kidneys

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

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Blood and nerve supply of the kidneys 



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Blood 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

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The nephron – functional units of kidney

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Nephrons 



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

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



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

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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

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Histology of a renal corpuscle

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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

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Overview of renal physiology 1.

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 

2.

3.

 

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Structures and functions of a nephron Renal tubule and collecting duct

Renal corpuscle Afferent arteriole

Glomerular capsule Urine (contains excreted substances)

Fluid in renal tubule

1 Filtration from blood plasma into nephron

2 Tubular reabsorption from fluid into blood

Efferent arteriole

Peritubular capillaries

3 Tubular secretion from blood into fluid Blood (contains reabsorbed substances)

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Glomerular filtration 

Glomerular filtrate – fluid that enters capsular space 



The filtration membrane

Daily volume 150-180 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.

Copyright 2009, John Wiley & Sons, Inc.

Podocyte of visceral layer of glomerular (Bowman’s) capsule

Net filtration pressure

Filtration slit Pedicel

1

Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through

2

Basal lamina of glomerulus: prevents filtration of larger proteins

3

Slit membrane between pedicels: prevents filtration of medium-sized proteins



Net filtration pressure (NFP) is the total pressure that promotes filtration  

(a) Details of filtration membrane

Pedicel of podocyte

Filtration slit





Basal lamina

Lumen of glomerulus

Fenestration (pore) of glomerular endothelial cell

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

TEM 78,000x

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(b) Filtration membrane

The pressures that drive glomerular filtration

1 GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg

2 CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg 3 BLOOD COLLOID OSMOTIC PRESSURE (BCOP) = 30 mmHg

Afferent arteriole

Proximal convoluted tubule

Efferent arteriole

NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg Glomerular (Bowman's) Capsular capsule space

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Glomerular filtration 

3 Mechanisms regulating GFR





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

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Too high – substances pass too quickly and are not reabsorbed Too low – nearly all reabsorbed and some waste products not adequately excreted

Tuboglomerular feedback

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Mechanisms regulating GFR Neural regulation

2. 









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Tubular reabsorption and tubular secretion

Reabsorption routes and transport mechanisms 

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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.

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

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Reabsorption – return of most of the filtered water and many solutes to the bloodstream 

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

3.



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

GFR directly related to pressures that determine net filtration pressure Copyright 2009, John Wiley & Sons, Inc.



Kidneys themselves maintain constant renal blood flow and GFR using

Homeostasis requires kidneys maintain a relatively constant GFR 



Renal autoregulation

1.

Glomerular filtration rate – amount of filtrate formed in all the renal corpuscles of both kidneys each minute

Reabsorption routes 

Paracellular reabsorption   

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

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

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Secondary active transport

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Sodium-potassium pumps in basolateral membrane only Symporters, antiporters



Transport maximum (Tm)

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Obligatory vs. facultative water reabsorption



Upper limit to how fast it can work

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Reabsorption routes: paracellular reabsorption and transcellular reabsorption

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+

  





Solute reabsorption promotes osmosis – creates osmotic gradient



 

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Reabsorption in the loop of Henle 

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

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

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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 ClMajor 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 

  

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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



Reabsorption and secretion in the proximal convoluted tubule

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

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.

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Hormonal regulation of tubular reabsorption and secretion 

Angiotensin II - when blood volume and blood pressure decrease 







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

Stimulates principal cells in collecting duct to reabsorb more Na+ and Cl- and secrete more K+



Stimulates cells in DCT to reabsorb more Ca2+

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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  

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

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

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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.

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

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Absent or low ADH = dilute urine Higher levels = more concentrated urine through increased water reabsorption

Formation of dilute urine

Increases water permeability of cells by inserting aquaporin-2 in last part of DCT and collecting duct

Atrial natriuretic peptide (ANP) 

Parathyroid hormone 

Antidiuretic hormone (ADH or vasopressin)

Decreases GFR, enhances reabsorption of Na+, Cl- and water in PCT

Aldosterone - when blood volume and blood pressure decrease 

Regulation of facultative water reabsorption by ADH

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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.

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Countercurrent multiplication 

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

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  

Countercurrent exchange

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



 





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

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Mechanism of urine concentration in longloop juxtamedullary nephrons

Vasa recta Loop of Henle Juxtamedullary nephron and its blood supply together

Glomerular (Bow man’s) capsule H2O Glomerulus

Afferent arteriole

Na +CI– Blood flow

Distal conv oluted tubule

Presense of Na +-K+-2CI– symporters Interstitial fluid in renal cortex

200

Efferent arteriole

300

H2O

H2O 300

300 100

320

380

200

3 Principal cells in

H2O

collecting duct reabsorb more w ater w hen ADH is present

Na +CI– Interstitial fluid in renal medulla

320

Collecting duct

300

H2O

400

Flow of tubular fluid

300

H2O

Proximal conv oluted tubule

H2O

Na +CI– 400

400

500

H2O

600

H2O 600

580

400

780

600

H2O

Na +CI– 600

1 Symporters in thick

Osmotic gradient

700

ascending limb cause buildup of Na + and Cl– 800

Urea

H2O 980

1000

H2O

800

800

H2O

800 900

4 Urea recycling 1000

causes buildup of urea in the renal medulla

Na +CI–

H2O 1000 1100

H2O 1200

through loop of Henle establishes an osmotic gradient

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Summary of filtration, reabsorption, and secretion in the nephron and collecting duct

1200

Loop of Henle

1200

Papillary duct

1200

Concentrated urine

(a) Reabsorption of Na +CI– and w ater in a long-loop j uxtamedullary nephron

1200

(b) Recycling of salts and urea in the v asa recta

Evaluation of kidney function 

Urinalysis 

 



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2 Countercurrent flow

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.

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Evaluation of kidney function 

Blood tests 





Urine transportation, storage, and elimination 

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

Ureters 



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

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

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Ireters, urinary bladder, and urethra in a female

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Urinary bladder and urethra 

Urinary bladder   

Hollow, distensible muscular organ Capacity averages 700-800mL Micturition – discharge of urine from bladder  





Urethra 



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Comparison between female and male urethras

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

Small tube leading from internal urethral orifice in floor of bladder to exterior of the body In males discharges semen as well as urine

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