SODIUM BALANCE

بسم الله الرحمن الرحيم

OVERALL HANDLING OF NA+

Na+ Reabsorption

• Of total energy spent by kidneys, 80% is used for

Na+ transport

• Na+ is not reabsorbed in the

descending limb of the loop of Henle

• In the early proximal tubule, Na+ is reabsorbed primarily with

HCO3- ,Glucose and Amino acids.

In the late proximal tubule, Na+ is reabsorbed primarily with Cl-,

What is Isosmotic Reabsorption• Solute and water reabsorption are coupled and

are proportional to each other. Thus, if 67% of the filtered solute is reabsorbed by the proximal tubule, then 67% of the filtered water also will be reabsorbed.

Glomerulotubular Balance ?

• Tubular reabsorption increases/decreases automatically as the filtered load increases/ decreases.

Glomerulotubular Balance----how?

Increase in GFR

Increase in filtration fraction Increase in concentration of protein in

peritubular capillaries

Increase in πc

Increase reabsorption in proximal tubule

Effects of ECF volume expansion & ECF volume contraction on isosmotic fluid reabsorption in the proximal tubule

Cellular mechanism of Na+ reabsorption in the early distal tubule

Late distal tubule

• Principal cell :Na+ reabsorption & K+ secretion

• α- inetercalted cells K+ reabsorption & H+ secretion

RAAS

Potassium, Calcium, Phosphate & Magnesium Balance

Internal potassium balance (continued)

Potassium handling by naphron

Potassium handling by nephron(continued)

Potassium handling by nephron(continued)

Distal tubule & collecting ducts :

α -Intercalated cells : absorption of potassium if person is on low K+ diet

Principle cells : if person on normal or high K+ diet potassium is excreted by principle cells

Factors affecting K+secretion Magnitude of K+ secretion is determined by

the size of electrochemical gradient across luminal membrane

Diet:High K+ diet concentration inside thus

principle cells increases electrochemical gradient across membrane

Factors affecting K+secretion(continued) Aldosterone :

Aldosterone Na+ re absorption by principle cell by inducing synthesis of luminal membrane Na+ channels & basolateral membrane Na+- K+ channel

more Na+ is pumped out of the cell simultaneously more K+ pumped into the cell

Thus increasing the electrochemical gradient for K+ across the luminal membrane that leads to increase K+ secretion

Relationship between Na+ absorption & K+ secretion High Na+ diet:

more Na+ will be delivered to principle cells ,more Na+ is available for Na+- K+ ATPase than more K+ is pumped into the cell which increases the driving force for K+ secretion

Factors affecting K+secretion(continued) Acid base disturbances :

The exchange of H+ & K+ ion across membrane underlies these effect

Alkalosis H+ in ECF H+ leaves & K+ enters the cell intracellular K+ contn driving force for K+

Acidosis H+ in ECF H+ enters & K+ leaves the cell intracellular K+ contn driving force forK+

Factors affecting K+secretion(continued) Diuretics :

Loop diuretics & thiazide diuretics causes hypokalemia

By decreasing the sodium re absorption in upstream to the site of K+ secretion ,make more Na+ available for the principle cells ,so more Na+ will be given out & more K+ will be taken in by Na+ - K+ ATPase

Increase flow rate luminal K+ contn diluted driving force for K+ secretion

Loop diuretics: also contribute to hypokalemia

by inhibiting Na+ - K+ -2cl co transport & thus K+ re absorption in thick ascending limb

K+ sparing diuretics: inhibits all of the action of aldosterone on

principle cells & therefore inhibits K+ secretion

Role of PTH

In the DCT ,PTH , Ca2+ reabsorption via basolateral receptor

activation of adenyl cyclase & generation of cyclic AMP

proximal tubule PTH inhibits phosphate re absorption by

inhibiting Na phosphate co transport As a result it causes phosphaturea

RENAL CLEARANCE AND RENAL BLOOD FLOW

If substance is filtered , not reabsorbed or secreted , its plasma clearance rate equals GFR

E.g Inuline

Clearance of Various SubstancesAlbumin – 0: normally albumin is not filtered across the membraneGlucose – 0 :normally filtered glucose is completely reabsorbed back into the blood streamInulin – is equal to the GFR.(Glomerular Marker) Inulin is a Fructose polymer ; freely filtered across the membrane and neither reabsorbed nor secreted.PAH – Para Amino Hippuric Acid(& other organic

acids).Has highest clearance since it is both filtered and secreted.

Clinically it is not convenient to use inline clearance so

Which substance is used instead

Creatinine

Calculation

CLEARANCE RATIO Clearance of any substance (x) compared with

clearance of Inulin = C x ( glomerular marker)

C inulinC x = 1 (filtered & neither reabsorbed nor

secreted) C inulinC x < 1 (substance is not filtered/filtered

& reabsorbed) C inulinC x > 1 (substance is filtered as well as

secreted ) C inulin

Sample problem

PAH Clearance is use to Estimate ? Renal Plasma Flow

ERPF = UPAH x V

PPAH

ERPF = Clearance PAH

~

~ 10 % PAHremains

Name Equation Units

Clearance Ux V

Px

mL/min

GFR U inulin x V P inulin

mL/min

Clearance Ratio

C x C inulin

None

Effective Renal Plasma Flow

U (PAH) x V P (PAH)

mL/min

Urine Concentration & Dilution

• The final adjustment of the urine volume and

osmolarity depends on the extent of facultative

water reabsorption in the Collecting Ducts, which

is depends on:-

– The blood level of antidiuretic hormone (ADH).

– The Medullary interstitium (MI) hypertonicity

(Medullary concentration gradient).

Medullary Countercurrent system• Juxta medullary nephrons

– vertical osmotic gradient in MI is estabilished by long loop of henle (Countercurrent multiplier) , – this gradient is preserved byvassa recta,( Countercurrent exchanger) – Which structure use the gradient in conjunction

with the hormone vassopressin, to produce urine of varying concentration ?

collecting ducts of all nephrones(osmotic equilibrating device) .

Countercurrent Multiplication• Comparing the descending and ascending limbs

of the loop of Henle

• The descending ling is highly permeable to water but does not extrude sodium for reabsorption.

• The ascending limb actively transports NaCl out of the tubular lumen into the surrounding interstitial fluid. It is impermeable to water. Therefore, water does not follow the salt by osmosis.

• There is a countercurrent flow produced by the close proximity of the two limbs.

Countercurrent MultiplicationThe descending limb

• is highly permeable to water

• but does not reabsorbs Na+

The ascending limb

• It is impermeable to water. Therefore, water does not follow the salt by osmosis.

• actively transports NaCl out of the tubular lumen into the surrounding interstitial fluid.

Countercurrent Multiplication

BENEFITS OF COUNTERCURRENT MULTIPLICATION

1. It establishes a vertical osmotic gradient in the medullary interstitial fluid. This gradient, in turn, is used by the collecting ducts to concentrate the tubular fluid so that a urine more concentrated than normal body fluids can be excreted.

2. Second, the fact that the fluid is hypotonic as it enters the distal parts of the tubule enables the kidneys to excrete a urine more dilute than normal body fluids.

Role of Vasopressin• Vasopressin-controlled, variable water reabsorption occurs in the

final tubular segments.

• 65 percent of water reabsorption is obligatory in the proximal tubule. In the distal tubule and collecting duct it is variable, based on the secretion of ADH.

• The secretion of vasopressin increases the permeability of the tubule cells to water. An osmotic gradient exists outside the tubules for the transport of water by osmosis.

• Vasopressin works on tubule cells through a cyclic AMP mechanism.

• During a water deficit, the secretion of vasopressin increases. This increases water reabsorption.

• During an excess of water, the secretion of vasopressin decreases. Less water is reabsorbed. More is eliminated.

Mechanism of action of Vasopressin

Regulation of H2O reabsorption in response to H2O deficit

Regulation of H2O reabsorption in response to H2O Excess

Reflex and Voluntary Control of Mictrurition

Abnormalities of micturition

Atonic Bladder Caused by Destruction of Sensory Nerve Fibers.• Micturition reflex cannot occur Person loses

bladder control• overflow incontinence.• A common cause of atonic bladder is crush

injury to the sacral region of the spinal cord.

• Automatic Bladder • Caused by Spinal Cord Damage Above the Sacral

Region.• Typical micturition reflexes can still occur. • Some patients can still control urination in this

condition by stimulating the skin (scratching or tickling) in the genital region, which sometimes elicits a micturition reflex.