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Production of Dilute andConcentrated Urine
• Homeostasis of body fluid volume dependsin large part on the ability of the kidneys toregulate the rate of water loss in urine.
• The kidneys produce a large volume ofdilute urine when fluid intake is high, and asmall volume of concentrated urine whenfluid intake is low or fluid loss from othersources is large.
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1. More and more water isreabsorbed by osmosis astubular fluid flows along thedescending limb so the fluidremaining in the lumenbecomes more concentrated.
2. Large numbers of solutes arereabsorbed in the thickascending limb and early DCTwhile the water permeabilityof this portion of the nephronis quite low. So the osmolaritywill decrease
3. Principal cells of the late DCTand CD are impermeable towater when the ADH level isvery low. Thus, tubular fluidbecomes progressively moredilute as it flows onward
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Formation of Diluted Urine
Formation of Concentrated Urine• When water intake is low or water loss is high, the kidneys
must conserve water while still eliminating wastes and excessions.
• Under the influence of ADH, the kidneys produce a smallvolume of highly concentrated urine.
• Urine can be four times more concentrated (up to 1200 mOsm/liter) than blood plasma or glomerular filtrate (300 mOsm/liter).
• The ability of ADH to cause excretion of concentrated urinedepends on
the presence of an osmotic gradient of solutes in the interstitialfluid of the renal medulla.▫ The solute concentration of the interstitial fluid in the kidney
increases from about 300 mOsm/liter in the renal cortex to about1200 mOsm/liter deep in the renal medulla.
▫ The three major solutes contribute to this high osmolarity are Na,Cl, and urea.
▫ Two main factors contribute to building and maintaining thisosmotic gradient:
1. Differences in solute and water permeability and reabsorptionin different sections of the long nephron loops and thecollecting ducts
h fl f fl id h h b h d
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Countercurrent Mechanisms• Countercurrent flow refers to the flow of fluid in
opposite directions. This occurs when fluidflowing in one tube runs counter (opposite) tofluid flowing in a nearby parallel tube.
• Examples of countercurrent flow include theflow of tubular fluid through the descendingand ascending limbs of the nephron loop andthe flow of blood through the ascending anddescending parts of the vasa recta.
• Two types of countercurrent mechanismsexist in the kidneys:
• Countercurrent multiplication: helps the longnephron loop to establish the osmotic gradientin the renal medulla
• Countercurrent exchange: helps the vasa rectato maintain the osmotic gradient in the renalmedulla
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Countercurrent Multiplication• Is the process by which a progressively
increasing osmotic gradient is formed in theinterstitial fluid of the renal medulla as a resultof countercurrent flow.
• Countercurrent multiplication involves the longnephron loops of juxtamedullary nephrons.
1. Symporters in thick ascending limb of loop ofHenle cause buildup of Na+ and Cl- in renalmedulla, cells impermeable to water
2. Countercurrent flow establishes gradient asreabsorbed Na+ and Cl- become increasinglyconcentrated
3. Cells in collecting duct reabsorb more waterand urea
4. Urea recycling causes a buildup of urea in therenal medulla
Long loop of Henle establishes gradient by
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Countercurrent Exchange• It is the process by which solutes and water are passively
exchanged between the blood of the vasa recta and interstitialfluid of the renal medulla
• The vasa recta consists of descending and ascending limbs thatare parallel to each other and to the nephron loop. Blood flowsin opposite directions in the ascending and descending partsof the vasa recta.
• Blood entering the vasa recta has an osmolarity of about 300mOsm/liter. As it flows along the descending part into therenal medulla, Na, Cl, and urea diffuse from interstitial fluidinto the blood and water diffuses from the blood into theinterstitial fluid.
• As the blood flows into the ascending part of the vasa recta, Na,Cl, and urea diffuse from the blood back into interstitial fluid,and water diffuses from interstitial fluid back into the vasarecta.
• The osmolarity of blood leaving the vasa recta is only slightlyhigher than the osmolarity of blood entering the vasa recta.
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Evaluation of Kidney Function• Routine assessment of kidney function
involves evaluating both the quantity andquality of urine and the levels of wastes inthe blood.
• Urinalysis
• Blood Tests▫ Blood urea nitrogen (BUN)▫ Plasma creatinine
• Renal Plasma Clearance
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Renal Plasma Clearance• The best test for evaluation of how effectively
the kidneys are removing a given substancefrom the blood.
• Renal plasma clearance is the volume of bloodthat is cleared of a substance per unit of time,usually expressed in units of milliliters perminute (ml/min).
• The following equation is used to calculateclearance:
• U and P are the concentrations of the substancein urine and plasma respectively (the unit mg/
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• Consider substance A that isfiltered but neither reabsorbednor secreted.
• Its clearance equals the GFRbecause all molecules that passthe filtration membrane appear inthe urine.
• This is the situation for the plantpolysaccharide inulin.
• GFR can be determined by givinginulin intravenously and thenmeasuring the concentrations ofinulin in plasma and urine. Andmeasuring the urine flow rate
• The clearance of creatinine canalso be used to assess GFR.
• Less accurate than inulin
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University of Jordan
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Calculate the GFR from thefollowing data:
Pinulin = 1.0 mg / 100mlUinulin = 125 mg/100 mlUrine flow rate = 1.0 ml/min
GFR = 125 x1.01.
0
= 125 ml/min
GFR = Cinulin
= Pi
n
Uin xV
Renal Plasma Clearance Example
• A 25 year old man weighing 60 kg has a plasma[creatinine] of 0.014 mg/ml. If you know thatUrine [creatinine] = 0.833 mg/ml and Urine flowrate = 0.75 ml/min
• What is his GFR?
• Creatinine clearance= (0.833 x 0.75)/ 0.014 =44.625 ml/min
• Creatinine Clearance ~ GFR• GFR = 44.625 ml/min
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Ureters• They are long, thick walled and narrow tubes.• They transport urine from the renal pelvis of
the kidney to the urinary bladder. Thismovement is achieved by:
1. Peristaltic contractions of the muscular walls ofthe ureters▫ This is the main mechanism
2. Hydrostatic pressure3. Effect of gravity
• As the urinary bladder fills with urine, pressurewithin it compresses the oblique openings intothe ureters and prevents the backflow of urine.
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Urinary Bladder• The urinary bladder is a hollow, distensible
muscular organ situated in the pelvic cavity.• It stores urine until it is excreted to the outside• Its capacity averages 700–800 mL
• It has an internal (involuntary) urethral sphincterand an external (voluntary) urethral sphincter
• The wall is made of three layers:1. Mucosa the innermost layer▫ Made of transitional epithelium and an underlying
lamina propria
2. Muscularis (detrusor muscle)▫ Consists of three layers of smooth muscle fibers
3. Adventitia a layer of areolar connective tissue
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Urethra• A small tube leading from the internal
urethral orifice in the floor of the urinarybladder to the exterior of the body.
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The Micturition Reflex
• Discharge of urine from the urinary bladder,called micturition or urination.
• Emptying of the urinary bladder is a reflexthat we learn to initiate it and stop itvoluntarily since early childhood.
• Micturition occurs through a spinal reflexcalled the micturition reflex
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Volume of urine exceeds 200–400mL
Large increase in the urinarypressure
Stimulation of stretch receptors withinthe wall
Signals are sent to micturition center in sacralspinal cord
Parasympathetic impulses
Urinary bladder wall Internal urethralsphincter
Contraction of the detrusormuscle
Relaxation of thesphincter
Micturation
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Acid–Base Balance
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Acid-base balance• The normal pH of systemic arterial blood is
7.35–7.45.• The overall acid–base balance of the body is
maintained by controlling the H+
concentration of body fluids, especiallyextracellular fluid.
• Metabolic reactions often produce a hugeexcess of H+, so several mechanisms helpmaintain the pH by eliminating the excessH+ :
• Buffer systems• Exhalation of carbon dioxide• Kidney excretion of H+
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Renal Regulation of Acid-BaseBalance
• Kidneys eliminate non-volatile acids (H2SO4,H3PO4)
• Filtration of HCO3-
• Reabsorption of HCO3-
• Production of new HCO3-
• Excretion of HCO3-
• Secretion of H+
• For each HCO3- reabsorbed, there must be a
H+ secreted
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Kidney Excretion of H+
• Cells in both the proximal convoluted tubules(PCT) and the collecting ducts (CD) of thekidneys secrete hydrogen ions into the tubularfluid.
• In the PCT, Na+–H+ antiporters secrete H+ as theyreabsorb Na+
• The apical membranes of intercalated cells ofthe CD include proton pumps (H+ ATPases)that secrete H+ into the tubular fluid.
� HCO3- produced by dissociation of H2CO3 inside
intercalated cells crosses the basolateralmembrane by means of Cl-–HCO3
- antiportersand then diffuses into peritubular capillaries
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• A second type of intercalated cell has proton pumps in itsbasolateral membrane and Cl-–HCO3
- antiporters in itsapical membrane.� They secrete HCO3
- and reabsorb H+.
• Thus, the two types of intercalated cells help maintain thepH of body fluids in two ways:
1. Excreting excess H+ when pH of body fluids is too low2. Excreting excess HCO3
- when pH is too high.
• Some H+ secreted into the tubular fluid of the collectingduct is buffered
• Two buffers combine with H+ in the collecting duct:1. HPO4
-2 (monohydrogen phosphate ion) the most plentifulbuffer in the tubular fluid of the collecting duct. H+
combines with it to form H2PO4- (dihydrogen phosphate
ion)2. NH3 (ammonia) H+ combines with it to form NH+
4(ammonium ion).
• Because these ions cannot diffuse back into tubule cells,they are excreted in the urine
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Renal vein mayhave a higher HCO3level than bloodentering the kidneyin the renal artery.
Most plentiful buffer in thetubular fluid
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The Actions of Buffer Systems• Buffers act quickly by temporarily binding to H+,
removing the highly reactive, excess H+ fromsolution.
• Buffers thus raise pH of body fluids but do notremove H+ from the body.
• Buffer solutions achieve their resistance to pHchange because of the presence of anequilibrium between the weak acid HA and itsconjugate base A−:
HA ⇌ H+ + A−
• When the concentration of H+ increases theequilibrium is shifted to the left. Because of this,
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Protein Buffer System• The most abundant buffer in intracellular
fluid and blood plasma.• Hemoglobin and albumin• When blood pH rises, the free carboxyl group
at one end of a protein releases H+:
• The H+ is then able to react with any excessOH- in the solution to form water.
• When blood pH falls, the free amino group atthe other end of a protein can combine withH+
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Carbonic Acid–Bicarbonate Buffer System
• It is based on the bicarbonate ion (HCO3-), which
can act as a weak base, and carbonic acid(H2CO3), which can act as a weak acid.
• If there is an excess of H+, the HCO3- can
function as a weak base and bind with H+ asfollows,
• Conversely, if there is a shortage of H+, theH2CO3 can function as a weak acid and provideH+, as follows:
• The kidneys synthesize new HCO3- and
reabsorb filtered HCO3-, this important buffer is
not lost in the urine.
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H2O +CO2
Exhalation of Carbon Dioxide• An increase in ventilation eliminates CO2 from
extracellular fluid, the reaction is driven to theleft, which reduces the H+ concentration, andblood pH increases. The opposite happens withdecreased ventilation.
• Changes in the rate and depth of breathing canalter the pH of body fluids within a couple of
i
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