urine dr a. villaflor

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URINE FORMATIONBlock VIII Module 1February 25, 2010

Dr. A. VillaflorGroup 2

THE KIDNEY- Regulate the composition and volume

of the plasma water.- Determines the composition and

volume of the extracellular fluidcompartment.

- Influence the intracellular fluidcompartment by continuous exchangeof water and solutes across all cellmembranes.

- Endocrine gland producingerythropoietin

- Regulation of BP: Renin-Angiotensin-Aldosterone System (RAAS): regulatesblood volume and amount of salt inthe body

Renal Blood supply- 21% of the cardiac output (1200

mL/min)- renal a --> interlobar a --> arcuate a

--> interlobular (radial) a --> afferentarterioles --> glomerular capillaries

--> efferent arterioles --> peritubularcapillaries --> interlobular v -->arcuate v --> interlobar v --> renal v

The Nephron- Functional unit- 1 million per kidney- Cannot regenerate- Physiologic loss of 10% per ten years

after age 40- The nephron

1. Glomeruluso

tuft of capillarieso Lined by epithelial cells

o Enclosed by Bowman’s capsule

o Filtering structure

2. Tubules

o Several segments

o Filtered fluid is processed toform urine

o Proximal, descending limb, loopof Henle, ascending thin,ascending thick, macula densa,early distal, late distal,connecting tubule, corticalcollecting, medullary collecting,large collecting ducts

- Regional differences:o Cortical (peritubular capillaries

surround the entire tubularsystem)

o Juxtamedullary nephrons (vasarecta form the long efferentarterioles)

URINE FORMATION- Glomerular filtration- Tubular reabsorption

- Tubular secretion

Mathematical expression:Urinary excretion rate= filtration rate – reabsorption rate +secretion rate

Glomerular filtration- Filtered fluid (glomerular filtrate is

protein-free with no cellular elements)- GFR is about 20% f the renal plasma

flow- Determined by balance of hydrostaticand colloid osmotic pressures, ANDcapillary filtration coefficient (K f )(permeability and filtering surfacearea)

Glomerular capillary membrane- Endothelium of the capillary- Basement membrane



- Podocytes – foot-like processes(epithelial cell layer) have gaps calledslit pores

- Primary point for restriction to plasmaproteins is the basement membrane

Filterability- Charge selective – negative

substances are filtered lesso Albumin can’t pass through

- Size selective – bigger substancesfilters less

o Water, Na + , and glucose arefiltered well

GFR = K f X net filtration pressure

Forces Favoring Filtration- Glomerular hydrostatic pressure (HPg)

= 60 mmHg

- Bowman’s capsule colloid osmoticpressure (OPb)

Forces Opposing Filtration- Bowman’s capsule hydrostatic

pressure (HPb) = 18 mmHg- Glomerular capillary colloid osmotic

pressure (OPg) = 32 mmHg

Net filtration pressure = HPg – HPb –OPg + OPb

= (60 – 18 – 32) mmHg

= +10 mmHg

GFR = K f X (HPg – HPb – OPg + OPb)

Increased GFR- Increased glomerular capillary

filtration coefficient- Increased glomerular capillary

hydrostatic pressureHPg – determined by

1. Arterial pressure2. Afferent arteriolar resistance3. Efferent arteriolar resistance

Increased glomerular hydrostatic pressure- Increases arterial pressure- Dilatation of afferent arterioles- Constriction of efferent arterioles (not

less than 3-fold increase in resistance)

Decreased GFR- Increased Bowman’s capsule

hydrostatic pressure (obstruction tothe urinary tract)

- Increased glomerular capillary colloidosmotic pressure1. Arterial plasma colloid osmotic

pressure

2. Fraction of plasma filtered byglomerular capillaries (filtrationfraction)

Decreased glomerular hydrostatic pressure- Decreased arterial blood pressure- Afferent arteriole constriction- More that 3-fold increase in efferent

arteriolar constriction or resistance

Increased capillary colloid pressure- Increased filtration fraction

1. Increase GFR2. Reduce renal plasma flow

RENAL BLOOD FLOW (RBF)- 1200 mL/ min- 21% of the cardiac output- RBF = renal artery pressure – renal

vein pressure / total renal vascularresistance

Renal artery pressure = systemic pressureRenal vein pressure = 3 to 4 mmHg

Total renal vascular resistance =interlobar, afferent and efferent arterioles

Renal vascular resistance controlled by:- Sympathetics- Hormones- Local internal renal control

mechanisms

Net filtration pressure = sum of hydrostatic and colloid osmotic forces thateither favour or oppose filtration acrossthe glomerular capillaries

K f = hydraulic conductivity and surfacearea of the glomerular capillaries



Physiologic control of GFR and RBF- Decrease GFR

1. Sympathetic activation2. Norepinephrine/epinephrine3. Endothelin

- Increase GFR1. Endothelial-derived nitric oxide2. Prostaglandins

Angiotensin – prevents drop inGFR

AUTOREGULATION OF GFR AND RENALBLOOD FLOW

Intrinsic feedback mechanismsaimed to keep RBF and GFR inconstant levels

- Maintain oxygen delivery- Maintain nutrient supply- Remove waste products of metabolism- Allow precise control of renal excretion

of water and solutes – prevent extremechanges in renal excretion

Glomerulotubular balance- Tubules increase reabsorption rate

in response in GFR Tubuloglomerular feedback

- Ensure relatively constant NaCldelivery to the distal tubules and

helps prevent spurious fluctuationin renal excretion1. Afferent arteriolar feedback

mechanism2. Efferent arteriolar feedback

mechanism

- Uses the juxtaglomerular complex– macula densa cells (initial distaltubule) and the juxtaglomerular

cells (walls of the afferent andefferent arterioles

Drop in NaCl delivery to the distal tubule---

Signal to the macula densa1. Afferent arteriolar dilatation –

increase GFR2. Increase renin release from the

juxtaglomerular cells – angiotensincascade – increase GFR

Myogenic Autoregulation of RBF and GFR- Ability of individual blood vessels toresist stretching during increasedarterial pressure

High protein intake increases RBF and GFRHigh blood glucose increases RBF and GFR

Arteriolarresistance Renal blood flow Net ultrafiltration

pressure

Control

Increased afferent

Decreasedafferent

Increased efferent

Decreasedefferent



Physiologic and pharmacologic factors with effects on glomerularhemodynamics

Afferentarteriolar

resistance

Efferentarteriolar

resistance

Renal bloodflow

Ultrafiltrationpressure K f GFR

Renalsympatheticnerves

EpinephrineAdenosine

CyclosporineNSAIDs

Angiotensin II

Endothelin-1

High proteindiet

Nitric Oxide

Atrialnatriuretricpeptide (ANP)

ProstaglandinsE2/I2

Calciumchannelblockers

ACE inhibitor /angiotensinreceptorblockers

Glomerular filtrate flow

Proximal tubule loop of Henle distalconvoluted tubule collecting tubulescollecting ducts URINE

Final urine composition

- Tubular reabsorption (mostsubstances, glucose, urea, Na + )

- Tubular secretion (K + , H + )

Urine Excretory rate

= glomerular filtration – tubular secretion+ tubular reabsorption

AmountFiltered

Amountreabsorb

ed

AmountExcreted

% of Filtered

loadReabsorb

edGlucose(g/day) 180 180 0 100

Bicarbonate(mEq/day)

4,320 4,318 2 >99.9

Sodium(mEq/day)

25,560 25,410 150 99.4

?

?

?

?

?

?

?



Chloride(mEq/day)

19,440 19,260 180 99.1

Urea(g/day) 46.8 23.4 23.4 50

Creatinine (g/day) 1.8 0 50 0

Tubular reabsorption- Quantitatively large

o Small change in GFR andtubular reabsorption canpotentially cause a largeurinary excretion of thatsubstance

o Not true in reality, GFR andreabsorption is closelycoordinated to prevent largefluctuations in urinary

excretion- Highly selectiveo Tubular segments control

the rate of reabsorption of each substanceindependently, for precisecontrol of the composition of the body fluids

Transport mechanisms- Transcellular- Paracellular- Ultrafiltration (bulk-flow) –

hydrostatic and colloid osmoticforces

- Passiveo Osmosiso Diffusion, facilitated diffusion

- Active transporto Primaryo Secondary (co-transport,

counter transport)



Solute and water transport in the loop of Henle

- Descending part of the thinsegment – highly permeable towater, moderately permeable tosolutes, simple diffusion occurs

- Thin ascending limb of the loop –less reabsorptive function

- Thick ascending limb of the loop –high metabolic activity, highlyreabsorptive function,impermeable to water

Distal tubule- Juxtaglomerular complex – first

part of the distal tubule, providesfeedback control of GFR and bloodflow

- Avid reabsorption of sodium,potassium, and chloride

- Impermeable to water and urea- Diluting segment

Late distal tubule and cortical collectingtubule

- Principal cellso Sodium reabsorption and

potassium secretionK + enters the cellbecause of thesodium-potassiumATPaseHigh intracellular K +

allows diffusion intothe luminal fluid

- Intercalated cellso Secrete hydrogen and

reabsorbed bicarbonate

H2O + CO 2 H2 CO 3 HCO 3 + H +

Absorbed secreted



Medullary collecting duct- Final site for urine processing- Permeability to water is controlled

by ADH- Permeable to urea- Secretes H + against a large

concentration gradient – role inacid-base regulation

The relative degree of reabsorption of solute versus the reabsorption of water ina tubular segment, determines theconcentration of that solute in the tubular fluid

Regulation of tubular reabsorption

1. Glomerulotubular balanceo Most basic controlling

mechanism for tubularreabsorption

o Intrinsic ability of the tubulesto increase reabsorption ratein response to increasedtubular load

o Occur independently of

hormoneso Prevent overloading of the

distal segments when GFRincreases

2. Colloid osmotic pressure of theplasma

o Systemic plasma colloidosmotic pressure increaseperitubular capillary colloidosmotic pressure increasesreabsorption

o Higher filtration fractionmeans greater fraction of plasma filtered, increasesplasma protein and thusincreases capillaryreabsorption rate

3. Peritubular capillary and renalinterstitial fluid physical forces

o High arterial pressureincreases peritubular

capillary hydrostaticpressure --- decreasereabsorption rate

o High resistance of theafferent and efferentarterioles decreases

capillary hydrostaticpressure --- increasereabsorption rate

4. Renal interstitial hydrostatic andcolloid osmotic pressure

o Increase renal interstitialfluid hydrostatic pressuredecreases interstitial fluidcolloid osmotic pressure,decreases net reabsorption

Hormone Site of Action Effects

Aldosterone Distal tubule/Collecting duct

NaCl, H 2Oreabsorption,

K + secretion

Angiotensin Proximal tubuleNaCl, H 2O

reabsorption,H+ secretion

Antidiuretichormone

Distal tubule/Collecting duct

H2Oreabsorption

Atrialnatriureticpeptide

Distal tubule/Collecting duct NaClreabsorption

Parathyroidhormone

Proximaltubules, thickascending loopof Henle/Distal tubules

PO 42-

reabsorptionCa ++

reabsorption

Sympathetic Nervous System- Activation constricts the afferent

and efferent arterioles, GFRdecreased

- Activation increases sodiumreabsorption in the proximaltubule, the ThAL

- Increases renin release andangiotensin II formation - increasetubular reabsorption

REGULATION OF ECF OSMOLARITY ANDSODIUM CONCENTRATION

Osmolarity



- Total concentration of solutes inthe ECF

- Amount of solutes divided by thevolume of ECF

- Regulated by ECF water

Total body water- Controlled by fluid intake

o Regulated by factors thatcontrol thirst

- Renal excretion of watero Controlled by factors that

influence GFR and tubularreabsorption

Renal ways of excreting water- Excess body water – urine

osmolarity can reach to 50 mOsm/L

(dilute)- Body water deficit – urineosmolarity can go as high as 1200to 1400 mOsm/L (concentrated)

- Excretion of a dilute oroncentration urine made withoutmajor changes in the excretion of solute (Na + or K + )

Antidiuretic hormone (ADH)- Vasopressin- Secreted by the posterior pituitary

gland- Alters renal excretion of waterindependently of the rate of soluteexcretion

- Allows more water reabsorption onthe distal and collecting tubulesand decreases the urine output

Diluting the urine- Glomerular filtrate osmolarity is

about the same as plasma (300mOsm/L)

- Proximal tubule – water and solutesare in equal proportionsreabsorbed

- Descending limb of the loop of Henle – water reabsorbed byosmosis making the tubular fluidhypertonic (until it equilibrates withthe surrounding interstitial fluid of the renal medulla) – about 4x theoriginal glomerular filtrateosmolarity

- Ascending limb of the loop of Henle – both the thin and the thick segments, ACTIVE reabsorption of Na + , K + , and Cl - while impermeableto water. Tubular fluid becomesdilute as it ascends the loop,(hypoosmotic). Osmolarity can beas low as 100 mOsm/L – 1/3 that of plasma, until the early distalconvoluted tubule

- Hypoosmolarity of the fluid in thissegment is independent of thepresence of ADH

SUMMARY:- Results from the continuous

reabsorption of solutes and failureof water reabsorption from the

distal tubules- Fluid leaving the ascending limb of the loop and early distal tubule isALWAYS DILUTE REGARDLESS OF

THE LEVEL OF ADH- Large amounts of dilute urine is

excreted, if ADH is absent, makingthe distal tubules which arecontinually reabsorbing solutes tobe impermeable to water

Concentrating the urine

Requirements:1. High levels of ADH2. High osmolarity of the renal

medullary interstitium – providesthe osmotic gradient needed forwater reabsorption in the presenceofADH

Medullary interstitium surrounding thecollecting ducts are NORMALLYHYPEROSMOTIC

The presence of ADH in high levels move

water from the collecting tubules to theinterstitiumWater is reabsorbed back into the blood

by the VASA NRECTA --- minimalamounts of concentrated urine

Creation of a hyperosmotic renalmedullary interstitium

- Operation of theCOUNTERCURRENT mechanism



- Special anatomical arrangement of the loops of Henle and vasa recta(specialised peritubular capillaries)--- 25% of human nephrons are

JUXTAGLOMERULAR – loops of Henle and vasa recta extendingdeep into the medulla, beforereturning back to the cortex

- Role of the collecting ducts

Countercurrent mechanism1. Interstitial fluids osmolarity in all

parts of the body – 300 mOsm/L.the same as the plasma

2. Interstitial fluid osmolarity of therenal medullary area – 1200 to1400 mOsm/L

3. It has accumulated large amounts

of solutes in greater excess of water

Role of Urea- Urea contributes about 40% (500

mOsm/L) of the renal medullaryinterstitium osmolarity

- Passively reabsorbed from theinner medullary collecting ducts

- Reabsorption: as water flows intothe ascending limb, into the distaland cortical collecting duct – zero

urea absorption due tiimpermeability of these tubules;with ADH, and consequent waterreabsorption to the interstitium,urea concentration inside thetubules increases. As the fluidreach the inner medullarycollecting duct, (permeable to ure),urea now diffuses into theinterstitium. ADH increases thepermeability of this segment tourea.

STEPS…1. Plasma flowing form the

descending limb of the vasa rectabecomes hyperosmotic

a. Water diffusion out of theblood

b. Solute diffusion from therenal interstitium into theblood

2. In the ascending limb of the vasarecta, solutes diffuse back into the

interstitium and water diffusesback into the vasa recta.

The ‘U’ shape capillary preventsthe loss of solutes from theinterstitium.

COUNTER CURRENT EXCHANGER The vasa recta does not create the

medullary hyperosmolarity, but preservesit by the diffusion of fluid and solutes intoand out of the medullary interstitium andthe blood.

Though it minimizes solute lossfrom the interstitium, it maintains itsabsorptive capacity through bulk flow dueto the colloid osmotic and hydrostaticpressures that favour reabsorption inthese capillaries.

THIN ASCENDING LOOP- Impermeable to water- More permeable to NaCl- Some passive diffusion of NaCl in

to the interstitium- The tubular fluid becomes more

dilute as it flows to the thicksegment

- Urea from the medullaryinterstitium (from the innermedullary collecting duct) diffuses

back into this segment THICK ASCENDING LOOP

- Impermeable to water- Active transport of electrolytes- Tubular fluid becomes dilute

ADH- Supraoptic and paraventricular

nuclei of hypothalamussynthesis

- Posterior pituitary storage

- Calcium entry in the nerve endingsincrease to affect membranepermeability when hypothalamicnuclei are stimulated ADHrelease

- AV3V – anteroventral region of the3 rd ventricle (subfonical organ andthe organum vasculosum of thelamina terminalis)



- Osmoreceptors – neuronal cellsexcited by changes in ECFosmolarity.

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urine dr a. villaflor

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