Clearance Measurements

Clearance compares the rate at which the glomeruli filter a substance with the rate that the kidneys excrete it into the urine.

If we measure difference in amount of substance filtered and excreted, we can estimate the net amount reabsorbed or secreted by renal tubules.

Gives us information about the 3 basic functions of the kidneys: Glomerular filtration Tubular reabsorption Tubular secretion

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Renal Clearance

Renal Clearance = plasma volume completely cleared of that substance per minute

Typically expressed as ml/min

Cs = Us x V Ps

Cs: Clearance rate of a substance sPs: Plasma concentration of the substanceUs: Urine concentration of that substance V: Urine flow rate

U (urea concentration in the urine) = 6mg/ml

V (rate of urine output) = 2 ml/minP (urea concentration in plasma) =

0.2mg/mlRenal clearance (C) is C = UV/P = 60 ml/min

• tests of renal clearance• inulin clearance test• creatinine clearance test• para-aminohippuric acid (PAH) test

• tests of renal clearance used to calculate glomerular filtration rate

Inulin clearance can be used to estimate GFR

GFR = Us x V = Cs Ps

P inulin = 1 mg/mlUrine inulin = 125 mg/mlV = 1 ml / minGFR = UV/P = 125 ml/min

Changes in average concentrations of different substances at different points in the tubular system relative to the concentration of that substance in the plasma and in the glomerular filtrate. A value of 1.0 indicates that the concentration of the substance in the tubular fluid is the same as the concentration of that substance in the plasma. Values below 1.0 indicate that the substance is reabsorbed more avidly than water, whereas values above 1.0 indicate that the substance is reabsorbed to a lesser extent than water or is secreted into the tubules

The Kidneys Excrete Excess Water by Forming a Dilute Urine

When there is excess water in the body and body fluid osmolarity is reduced, the kidney can excrete urine with an osmolarity as low as 50 mOsm/L

When there is a deficit of water and extracellular fluid osmolarity is high, the kidney can excrete urine with a concentration of 1200 to 1400 mOsm/L

Kidney regulate water excretion independently of solute excretion

Antidiuretic Hormone Controls Urine Concentration

Antidiuretic hormone (ADH): when osmolarity of the body fluids increases above normal more ADH will secreted

When there is excess water in the body and extracellular fluid osmolarity is reduced, the secretion of ADH by the posterior pituitary decreases

The rate of ADH secretion determines whether the kidney excretes a dilute or a concentrated urine

Water diuresis in a human after ingestion of 1 liter of water. After water ingestion, urine volume increases and urine osmolarity decreases, causing the excretion of a large volume of dilute urine; however, the total amount of solute excreted by the kidneys remains relatively constant. These responses of the kidneys prevent plasma osmolarity from decreasing markedly during excess water ingestion

Formation of a dilute urine when antidiuretic hormone (ADH) levels are very low. The ascending loop of Henle, the tubular fluid becomes very dilute. In the distal tubules and collecting tubules, the tubular fluid is further diluted by the reabsorption of sodium chloride and the failure to reabsorb water when ADH levels are very low. The failure to reabsorb water and continued reabsorption of solutes lead to a large volume of dilute urine

Requirements for Excreting a Concentrated Urine-High ADH Levels and Hyperosmotic Renal Medulla Body

The basic requirements for forming a concentrated urine are

(1) a high level of ADH, which increases the permeability of the distal tubules and collecting ducts to water

(2) a high osmolarity of the renal medullary interstitial fluid, which provides the osmotic gradient necessary for water reabsorption to occur in the presence of high levels of ADH

Countercurrent Mechanism

The countercurrent mechanism depends on the special arrangement of the loops of Henle and the vasa recta, the specialized peritubular capillaries of the renal medulla.

The collecting ducts, which carry urine through the hyperosmotic renal medulla before it is excreted, also play a critical role in the countercurrent mechanism

Countercurrent Mechanism Produces a Hyperosmotic Renal Medullary Interstitium

Factors contribute to built up of solute concentration: Active transport of sodium ions and co-transport of

potassium, chloride, and other ions out of the thick portion of the ascending limb of the loop of Henle into the medullary interstitium

Active transport of ions from the collecting ducts into the medullary interstitium

Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into the medullary interstitium

Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium far less than the reabsorption of solutes into the medullary interstitium

Summary of tubule characteristics

Active NaCl transport

PermeabilityH2O NaCl Urea

Proximal tubule ++ ++ + +

Thin descending limb

0 ++ + +

Thin ascending limb

0 0 + +

Thick ascending limb

++ 0 0 0

Distal tubule + +ADH 0 0

Cortical collecting tubule

+ +ADH 0 0

Inner medullary collecting duct

+ +ADH 0 ++ADH0, minimal level of active transport or permeability; +, moderate level of active transport or permeability; ++, high level of active transport or permeability; +ADH, permeability to water or urea is increased by ADH.

Countercurrent multiplier system in the loop of Henle for producing a hyperosmotic renal medulla