05 Urine Concentration - Vt

7/27/2019 05 Urine Concentration - Vt

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URINE CONCENTRATIONThe rates at which different substances areexcreted in the urine represent the sum of 3renal process:1. glomerular filtration2. reabsorbtion of substances from the renaltubules into the blood.3. secretion of substances from the blood intothe renal tubules

Renal handling of 4 hypotheticalsubstances:1. Filtration only

substance freely filtered but notreabsorbed nor secreted.

Excretion rate=filtration rate

e.g. creatinine2. Filtration with partial reabsorption

substance is freely filtered but part ofthe filtered load is reabsorbed back tothe blood

excretion rate = filtration rate-reabsorption rate

e.g. sodium, chloride3. Filtration with complete reabsorption

substance is freely filtered but isexcreted in the urine because all thefiltered substance is reabsorbed fromthe tubules into the blood

e.g. amino acids, glucose4. Filtration and Secretion

substance is freely filtered and is not

absorbed but is secreted from theperitubular capillary blood into the renaltubules.

Excretion rate = filtration rate+tubularsecretion rate

e.g. organic acids and bases

Glomerular filtration- first step in urine production- water and most solutes in blood plasmamove across the wall of glomerular capillariesinto the glomerular capsule then into the renal

tubule- 125 ml/min or 180 L/day- depends on three pressures:A. Glomerular hydrostatic pressure

blood pressure in glomerular capillaries

promotes filtration by forcing water and

solutes in blood plasma through thefiltration membrane

60 mmHg

B. Bowman's capsule hydrostaticpressure

pressure exerted against the filtration

membrane by fluid already in the

capsular space and renal tubule

opposes filtration and representback pressure

18 mmHg

C. Glomerular Oncotic pressure

due to the pressure of prot

(albumin,globulins, and fibrinogenblood plasma

opposes filtration

18 mmHg

Net filtration Pressure (NFP)the total pressure that promotes filtratiodetermined as follows:NFP = Glomerular hydrostatic pressurBowman's capsule hydrostatic pressurGlomerular oncotic pressure

Glomerular Filtration Rate

125 ml/m or 160 L/day

directly related to the pressures determine net filtration pressure; change in NFP will affect GFR

if GFR is too high, needed substan

may pass so quickly through the rtubules that some are not absorbedare lost in the urine

if GFR is too low, nearly all the filt

may be reabsorbed and certain wproducts may not be adequaexcreted

Renal Autoregulation the kidneys itselves help maintain

constant renal blood flow and despote normal, everyday changeblood

consists of 2 mechanisms:1. Myogenic Mechanism

changes in renal perfusion pres(RPP) sensed by smooth muelements that serve as baroreceptothe afferent glomerular arterioleadjusting transmural pressure

tension across the arteriolar wall2. Tubuloglomerular Feedback

a stimulus received at the macula de

would me transmitted to the arteriof the same nephron to alter GFR

Each nephron regulate its own GFR

as a consequence, whole kidney

and secondarily RBF are autoregulat

increase in renal artery pressurincreased tubular fluid flow rate inloop, and macula densa increa

delivery of solutes (Na, Cl) to ma


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densa vasoconstrictor mediators(angiotensin II, prostaglandins,adenosine) afferent arteriolarconstriction: reduced RBF, glomerularpressure, and GFR

Hormonal RegulationA. Angiotension II

stimulus: decreased blood flow or blood

pressure

constriction of both afferent andefferent arterioles

decreased GFR

B. Atrial Natriuretic Peptide

stretching of the atria of the heart

relaxation of mesangial cells in

glomerulus increases capillary surfacearea available for filtration

increase GFR

REABSORPTIONTubular reabsortion:

2 step process: lumen to interstitium

and interstitium to peritubular capillary

routes: paracellular or transcellular

Reabsorption

Highly selective (complete, partial, or

poor reabsorption)

by controlling the reabsorption rate of

different substances, the kidneysregulate the excretion of solutesindependently of one another forprecise control of the body fluidcomposition

Transport Mechanisms:

simple diffusion (across gradient) simple facilitated diffusion (channels)

secondary active transport (co-transporters)

primary active transport (coupled with

ATP)

Endocytosis (form of primary activetransport)

Limits on the rate of transport1. Transport maximum (Tmax)

maximal tubular transport

capacity (max rate at whicsubstance can be reabsoregardless of the lumconcentration)

Due to saturabilitytransporters

glucose Tmax = 375 (male), mg/min (female) equivalenplasma glucose ~200 mg/dl

Glucose (or any similar solut

excreted before the Tmaxreached splay

2. Gradient-Limited Systems

the epithelium has a fpassive permeability to substance, usually through tight junctions, a lconcentration gradient betwthe interstitium and lumen rein a large passive flux baleak

Regulation of reabsorptionA. Glomerulotubular balance

- changes in GFR are balancedequivalent changes in tubreabsorption, thus maintainingconstant fractional reabsorptiofluid and NaCl

- Although the distal nephroncapable of adjusting reabsorptioresponse to changes in tubular fthe impact of GFR on reabsorption by the proxi

tubule is particularly pronounced- independent of direct neurohum

controlB. Peritubular capillary and re

interstitial fluid physical forces- Hydrostatic and colloid osm

forces govern the rate reabsorption across the peritubcapillaries

- Changes in peritubular capireabsorption can in turn influethe hydrostatic and colloid osm

pressures of the renal interstiand tubular reabsorption of wand solutes

C. Pressure natriuresis and pressdiuresis- Even small increases in art

pressure can cause maincreases in urinary excretionsodium and water

- When increased renal artpressure raises urine outpudecreases the percentage of

filtered load of sodium and w


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that is reabsorbed by the tubules

D. Hormonal control

SECRETIONTubular secretion

Initial step is simple diffusion (or bulkflow) from the peritubular capillaries tothe interstitial fluid

Then solute gains entry to the tubule

either by Simple diffusion through tight

junctions

Active transport through the cells

Segmental nephron functionsPROXIMAL TUBULE

Main reabsorptive region of the nephron

Reabsorbs >100 L/day (55-60% of dailyfiltration rate of 180 L)

Due to expanded surface area available

for reabsorptive work (brush border),and leaky tight junctions enabling high-capacity fluid reabsorption

Reabsorption occurring in the PT isisosmotic

Reabsorption of:

~60% of filtered NaCl & water,

~90% of filtered bicarbonate

all of filtered glucose & aminoacids (Na cotransport),

potassium, calcium, phosphate,magnesium, urea, uric acid

Secretion of:

organic anions (such as urate)and cations, inluding manyprotein-bound drugs

ammonia (major site of ammoniaproduction)

LOOP OF HENLE

Reabsorbs

~ 1525% of filtered NaCl,mainly by the ThAL

calcium and magnesium

ions

Major site of active regulatiomagnesium excretion

Thin descending limb is hiwater-permeable

Thin ascending limb negligible water permeability

Critical role in uriconcentrating ability contributing to the generatio

a hypertonic meduinterstitium (countercurmultiplication)

DISTAL CONVOLUTED TUBULE

Reabsorbs ~5% of the filtered Na

Apical thiazide-sensitive Na+/Cl

transporter in tandem basolateral Na+/K+-ATPase andchannels

Major site (together with connecsegment) of active regulationcalcium excretion

Tight epithelium with little wpermeability

COLLECTING DUCT

CCD and IMCD

reabsorbs~45% of filtered Na+

important for hormonal regulatiosalt and water balance

CCD has high-resistance epith

with two cell types.11 Principal cell

Reabsorbs Na+ and Cl-

Secretes K+ (partly uthe influence aldosterone)

11 Intercalated cell

Type A - acid secrebicarbonate & reabsorption

Type B - bicarbosecretion, reabsorption

IMCD

Site of final modification of urine

Reabsorbs NaCl (apical Na chann

Secretes or reabsorbs K+ (apicchannel)

Reabsorbs water and urea (relato vasopressin present) allowindilute or concentrated urine to

excreted


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Secretes H+ and NH3 (urine pH canbe reduced to 4.5 to 5)

Regulation of water excretion

Water excretion = volume of waterfiltered - volume reabsorbed

Determinants:

Rate of water reabsorption(not the rate at which it isfiltered) major regulated

determinant ADH secretion

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05 Urine Concentration - Vt