University of Jordan1 Renal system Faisal I. Mohammed, MD, PhD Yanal Shafagoj, MD, PhD

University of Jordan 1

Renal system

Faisal I. Mohammed, MD, PhD

Yanal Shafagoj, MD, PhD


Tubular reabsorption and tubular secretion Reabsorption – return of most of the filtered

water and many solutes to the bloodstream About 99% of filtered water reabsorbed Proximal convoluted tubule cells make largest

contribution Both active and passive processes

Secretion – transfer of material from blood into tubular fluid Helps control blood pH Helps eliminate substances from the body (K+)


Reabsorption routes and transport mechanisms Reabsorption routes

Paracellular reabsorption Between adjacent tubule cells Tight junction do not completely seal off interstitial fluid from tubule

fluid Passive

Transcellular reabsorption – through an individual cell Transport mechanisms

Reabsorption of Na+ especially important Primary active transport

Sodium-potassium pumps in basolateral membrane only Secondary active transport

Symporters, antiporters Transport maximum (Tm)

Upper limit to how fast it can work Obligatory vs. facultative water reabsorption


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

+ Most solute reabsorption involves Na+

Symporters with glucose, amino acids, lactic acid, water-soluble vitamins, phosphate and sulfate

Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be secreted Solute reabsorption promotes osmosis – creates osmotic gradient

Aquaporin-1 in cells lining PCT and descending limb of loop of Henle As water leaves tubular fluid, solute concentration increases

Urea and ammonia in blood are filtered at glomerulus and secreted by proximal convoluted tubule cells


Reabsorption and secretion in the proximal convoluted tubule


Reabsorption in the loop of Henle

Chemical composition of tubular fluid quite different from filtrate Glucose, amino acids and other nutrients were already

reabsorbed in PT At the entranc of LH Osmolarity still close to that of blood

Reabsorption of water and solutes balanced In the descending: 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 Ascending: Na+-K+-2Cl- symporters function in Na+ and Cl-

reabsorption – promotes reabsorption of cations No water is reabsorbed in ascending limb – osmolarity

decreases


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


Reabsorption and secretion in the late distale convoluted tubule and collecting duct Reabsorption on the early distal convoluted tubule

Na+-Cl- symporters reabsorb Na+ and Cl- (Thiazide) Major site where parathyroid hormone stimulates

reabsorption of Ca+ depending on body’s needs Reabsorption and secretion in the late distal

convoluted tubule and collecting duct 90-95% of filtered solutes and fluid have been returned by

now Principal cells reabsorb Na+ and secrete K+

Intercalated cells reabsorb K+ and HCO3- and secrete H+

Amount of water reabsorption and solute reabsorption and secretion depends on body’s needs


Hormonal regulation of tubular reabsorption and secretion

Angiotensin II - when blood volume and blood pressure decrease Decreases GFR, enhances reabsorption of Na+, Cl- and water

in PCT Aldosterone - when blood volume and blood pressure

decrease Stimulates principal cells in collecting duct to reabsorb more

Na+ and Cl- and secrete more K+ (Aldactone) Parathyroid hormone

Stimulates cells in DCT to reabsorb more Ca2+


Regulation of facultative water reabsorption by ADH

Antidiuretic hormone (ADH or vasopressin) Increases water

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

Atrial natriuretic peptide (ANP) Large increase in blood

volume promotes release of ANP

Decreases blood volume and pressure by inhibiting reabsorption of Na+ and water in PCT and collecting duct, suppress secretion of ADH and aldosterone

ANP

Produced by atria due to stretching of walls. Antagonist to aldosterone. Increases Na+ and H20 excretion. Acts as an endogenous diuretic.


Production of dilute and concentrated urine Even though your fluid intake can be highly

variable, total fluid volume in your body remains stable

Depends in large part on the kidneys to regulate the rate of water loss in urine

ADH controls whether dilute or concentrated urine is formed Absent or low ADH = dilute urine Higher levels = more concentrated urine through

increased water reabsorption


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


Formation of dilute urine

Osmolarity of interstitial fluid of renal medulla becomes greater, more water is reabsorbed from tubular fluid so fluid become more concentrated

Water cannot leave in thick portion of ascending limb but solutes leave making fluid more dilute than blood plasma

Additional solutes but not much water leaves in DCT

Low ADH makes late DCT and collecting duct have low water permeability


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


Countercurrent multiplication

Process by which a progressively increasing osmotic gradient is formed as a result of countercurrent flow

Long loops of Henle of juxtamedullary nephrons function as countercurrent multiplier

Symporters in thick ascending limb of loop of Henle cause buildup of Na+ and Cl- in renal medulla, cells impermeable to water

Countercurrent flow establishes gradient as reabsorbed Na+ and Cl- become increasingly concentrated

Cells in collecting duct reabsorb more water and urea Urea recycling causes a buildup of urea in the renal medulla Long loop of Henle establishes gradient by countercurrent

multiplication


Countercurrent exchange

Process by which solutes and water are passively exchanged between blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow

Vasa recta is a countercurrent exchanger Osmolarity of blood leaving vasa recta is only

slightly higher than blood entering Provides oxygen and nutrients to medulla without

washing out or diminishing gradient Vasa recta maintains gradient by countercurrent

exchange


Mechanism of urine concentration in long-loop juxtamedullary nephrons

University of Jordan 20(b) Recycling of salts and urea in the vasa recta(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron

Glomerular (Bowman’s) capsule

Afferentarteriole

Efferentarteriole

Glomerulus

Distal convoluted tubule

Proximalconvolutedtubule

Symporters in thickascending limb causebuildup of Na+ and Cl–

Interstitial fluidin renal medulla

300

1200

1000

800

Osmoticgradient

600

400

H2OH2O

H2O

200

1200

980

600780

400580

200380

300

100

Loop of Henle1200 Concentrated urine

300

300

320

400

600

800

1000

1200

800

H2O

Urea

Papillaryduct

Collectingduct

300

500

700

900

1100

1200

400

800

1000

600

Na+CI–

Blood flow

Flow of tubular fluid

Presense of Na+-K+-2CI–

symportersInterstitialfluid inrenal cortex

320

Juxtamedullary nephronand its blood supply together

Vasarecta

Loop ofHenle

H2O

H2O

H2O

H2O

H2O

H2O

H2O

1

H2O

H2O

Na+CI–

Na+CI–

H2O

Na+CI–

H2O

Na+CI–

(b) Recycling of salts and urea in the vasa recta(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron


Afferentarteriole

Efferentarteriole

Glomerulus





300

1200

1000

800

Osmoticgradient

600

400

H2OH2O

H2O

200

1200

980

600780

400580

200380

300

100


300

300

320

400

600

800

1000

1200

800

H2O

Urea

Papillaryduct

Collectingduct

Countercurrent flowthrough loop of Henleestablishes an osmoticgradient

300

500

700

900

1100

1200

400

800

1000

600

Na+CI–

Blood flow




320


Vasarecta

Loop ofHenle

H2O

H2O

H2O

H2O

H2O

H2O

H2O

1

2

H2O

H2O

Na+CI–

Na+CI–

H2O

Na+CI–

H2O

Na+CI–



Afferentarteriole

Efferentarteriole

Glomerulus





300

1200

1000

800

Osmoticgradient

600

400

H2OH2O

H2O

200

1200

980

600780

400580

200380

300

100


300

300

320

400

600

800

1000

1200

800

H2O

Urea

Papillaryduct

Collectingduct


Principal cells incollecting ductreabsorb morewater when ADHis present

300

500

700

900

1100

1200

400

800

1000

600

Na+CI–

Blood flow




320


Vasarecta

Loop ofHenle

H2O

H2O

H2O

H2O

H2O

H2O

H2O

1

2

3

H2O

H2O

Na+CI–

Na+CI–

H2O

Na+CI–

H2O

Na+CI–



Afferentarteriole

Efferentarteriole

Glomerulus





300

1200

1000

800

Osmoticgradient

600

400

H2OH2O

H2O

200

1200

980

600780

400580

200380

300

100


300

300

320

400

600

800

1000

1200

800

H2O

Urea

Papillaryduct

Urea recyclingcauses buildupof urea in therenal medulla

Collectingduct


Principal cells incollecting ductreabsorb morewater when ADHis present

300

500

700

900

1100

1200

400

800

1000

600

Na+CI–

Blood flow




320


Vasarecta

Loop ofHenle

H2O

H2O

H2O

H2O

H2O

H2O

H2O

1

2

3

4

H2O

H2O

Na+CI–

Na+CI–

H2O

Na+CI–

H2O

Na+CI–


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

Na+ Reabsorption

90% filtered Na+ reabsorbed in PCT.

In the absence of aldosterone, 80% of the remaining Na+ is reabsorbed in DCT.

Final [Na+] controlled in CD by aldosterone.

When aldosterone is secreted in maximal amounts, all Na+ in DCT is reabsorbed.

Insert fig. 17.26

K+ Secretion

90% filtered K+ is reabsorbed in early part of the nephron.

Secretion of K+ occurs in CD. Amount of K+ secreted depends upon:

Amount of Na+ delivered to the region. Amount of aldosterone secreted.

As Na+ is reabsorbed, lumen of tubule becomes –charged. Potential difference drives secretion of K+ into tubule.

Transport carriers for Na+ separate from transporters for K+.

K+ Secretion (continued)

Final [K+] controlled in CD by aldosterone. When

aldosterone is absent, no K+ is excreted in the urine.

High [K+] or low [Na+] stimulates the secretion of aldosterone.

Only means by which K+ is secreted.

Insert fig. 17.24

Renal Acid-Base Regulation

Kidneys help regulate blood pH by excreting H+ and reabsorbing HC03

-. Most of the H+ secretion occurs across the

walls of the PCT in exchange for Na+. Antiport mechanism.

Moves Na+ and H+ in opposite directions.

Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03

- and excrete H+. Returns blood pH back to normal range.

Reabsorption of HCO3-

Apical membranes of tubule cells are impermeable to HCO3

-. Reabsorption is indirect.

When urine is acidic, HCO3- combines with H+

to form H2C03-, which is catalyzed by ca

located in the apical cell membrane of PCT. As [C02] increases in the filtrate, C02 diffuses into

tubule cell and forms H2C03. H2C03 dissociates to HCO3

- and H+. HCO3

- generated within tubule cell diffuses into peritubular capillary.

Acidification of Urine

Insert fig. 17.28

Urinary Buffers

Nephron cannot produce a urine pH < 4.5. In order to excrete more H+, the acid must be

buffered. H+ secreted into the urine tubule and

combines with HPO4-2 or NH3.

HPO4-2 + H+ H2PO4

-

NH3 + H+ NH4+

Diuretics

Increase urine volume excreted. Increase the proportion of glomerular filtrate that is excreted as

urine.

Loop diuretics: Inhibit NaCl transport out of the ascending limb of the LH.

Thiazide diuretics: Inhibit NaCl reabsorption in the 1st segment of the DCT.

Ca inhibitors: Prevent H20 reabsorption in PCT when HC0s

- is reabsorbed.

Osmotic diuretics: Increase osmotic pressure of filtrate.

Clinical Diuretics Sites of Action

Insert fig. 17.29


Evaluation of kidney function

Urinalysis Analysis of the volume and physical, chemical

and microscopic properties of urine Water accounts for 95% of total urine volume Typical solutes are filtered and secreted

substances that are not reabsorbed If disease alters metabolism or kidney function,

traces if substances normally not present or normal constituents in abnormal amounts may appear


Evaluation of kidney function

Blood tests Blood urea nitrogen (BUN) – measures blood nitrogen that

is part of the urea resulting from catabolism and deamination of amino acids

Plasma creatinine results from catabolism of creatine phosphate in skeletal muscle – measure of renal function

Renal plasma clearance More useful in diagnosis of kidney problems than above Volume of blood cleared of a substance per unit time High renal plasma clearance indicates efficient excretion of

a substance into urine PAH administered to measure renal plasma flow


Urine transportation, storage, and elimination Ureters

Each of 2 ureters transports urine from renal pelvis of one kidney to the bladder

Peristaltic waves, hydrostatic pressure and gravity move urine

No anatomical valve at the opening of the ureter into bladder – when bladder fills it compresses the opening and prevents backflow


Ireters, urinary bladder, and urethra in a female


Urinary bladder and urethra

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

Combination of voluntary and involuntary muscle contractions When volume increases stretch receptors send signals to

micturition center in spinal cord triggering spinal reflex – micturition reflex

In early childhood we learn to initiate and stop it voluntarily Urethra

Small tube leading from internal urethral orifice in floor of bladder to exterior of the body

In males discharges semen as well as urine


Comparison between female and male urethras

Glucose and Amino Acid Reabsorption

Filtered glucose and amino acids are normally reabsorbed by the nephrons. In PCT occurs by secondary active transport with

membrane carriers. Carrier mediated transport displays:

Saturation. Tm.

[Transported molecules] needed to saturate carriers and achieve maximum transport rate.

Renal transport threshold: Minimum plasma [substance] that results in

excretion of that substance in the urine. Renal plasma threshold for glucose = 180-200 mg/dl.

Kidney Diseases

Acute renal failure: Ability of kidneys to excrete wastes and regulate

homeostasis of blood volume, pH, and electrolytes impaired. Rise in blood [creatinine]. Decrease in renal plasma clearance of creatinine.

Glomerulonephritis: Inflammation of the glomeruli. Autoimmune disease by which antibodies have been

raised against the glomerulus basement membrane. Leakage of protein into the urine.

Kidney Diseases (continued)

Renal insufficiency: Nephrons are destroyed. Clinical manifestations:

Salt and H20 retention. Uremia. Elevated plasma [H+] and [K+].

Dialysis: Separates molecules on the basis of the ability to

diffuse through selectively permeable membrane.


Documents

University of Jordan1 Renal system Faisal I. Mohammed, MD, PhD Yanal Shafagoj, MD, PhD