RENAL SYSTEM PHYSIOLOGY Dr Shahab Shaikh PhD, MD Lecture – 4: Tubular Reabsorption - 2 •••••••••••••••••••••••••••••••••• College of Medicine Al Maarefa Colleges of Science & Technology

OBJECTIVES Qualitatively describe the forces that determine movement of reabsorbed fluid from interstitium into peritubular capillaries. State the major characteristics of the proximal-tubular systems for active reabsorption of organic nutrients. Understand pressure natriuresis, pressure diuresis and osmotic diuresis. List the approximate percentages of the filtered load of sodium reabsorbed by the various tubular segments. Understand the active step of sodium reabsorption in all sodium-reabsorbing segments. Understand the mechanisms of water reabsorption. Understand the water permeability characteristics of each tubular segment. Understand the maximum urinary osmolarity. Define obligatory water loss, and understand its determinants.

Urine Formation Three Basic Mechanisms (Renal Processes) of Urine Formation include: Glomerular filtration - GF Tubular reabsorption - TR Tubular secretion - TS

Tubular Reabsorption Some Major Substances Reabsorbed: Sodium Water Glucose Amino acid Bicarbonate Phosphate Urea

Tubular Reabsorption – Glucose & AA Glucose and Amino Acid (AA) reabsorption is by secondary active transport (with Na+). Both Glucose and AA are filtered by glomeruli but all are reabsorbed in PCT with Na+ (secondary active transport). In normal person, there is no glucose and amino acids in urine. For both glucose and amino acid specialized Symport carrier, such as Na+ and glucose co-transporter (SGLT) is present in PCT and transfers both Na+ and glucose from lumen to the cell. The Na+ - K+ pump operating at basolateral membrane drives the co-transport system at the lumen

Tubular Reabsorption – Glucose Tubular Maximum (Tm): Tubular maximum refers to the upper limit on transport of a substance across the kidney tubules when all of the carriers specific for the substance are saturated. Any quantity of a substance filtered beyond its Tm is not reabsorbed and escapes into the urine. In general, all actively reabsorbed substances exhibit a tubular maximum. Renal threshold: The plasma concentration at which the Tm of a particular substance is reached and the substance first starts appearing in the urine is called the renal threshold.

Tubular Reabsorption – Glucose Tubular Maximum (Tm) of Glucose: Tm for glucose is 375 mg/minute. When the filtered load of glucose becomes more than this Tm value, Glucose appears in urine. Renal threshold for Glucose: Renal threshold is the plasma concentration of glucose at which glucose will appear in the urine, it is 180mg % - 200mg %. Because at this renal threshold (180mg % - 200mg % in plasma) Tm of glucose is reached, therefore, glucose appears in the urine. This is the reason why Glycosuria occurs in many DM patients even before there is any real damage to kidneys in DM (Diabetic Nephropathy) Ideally the renal threshold for Glucose should have been 375 mg/100ml but it is not so. Why & Why?

Tubular Reabsorption – Glucose Tubular Maximum (Tm) & Renal threshold for Glucose: Splay In the renal handling of glucose curve, the Tm is approached somewhat gradually, along a curve, rather than abruptly with a sharp deflection. The curve is known as the splay. Splay: has two possible explanations. Because the carrier has a finite affinity for glucose, a saturating concentration of glucose in the tubular fluid is needed to occupy all sites for glucose on the carrier. Hence, glucose is spilled in the urine before the TM is reached, and splay results. 2. In any one person there may be an eightfold difference in the glomerular surface area available for filtration, and a twofold to threefold variation in the volume of the proximal tubule. Unless the glucose-reabsorptive capacity of each proximal tubule is tailored precisely to the glucose filtering capacity of its own glomerulus, some nephrons will excrete glucose before TMGluc for most nephrons is reached, and other nephrons will continue to reabsorb after TMGluc has been exceeded.

Tubular Reabsorption – Urea Urea is produced continuously by the liver as an end product of protein metabolism. Urea is a waste substance that is eliminated to maintain nitrogen balance and is also a useful (necessary) factor in controlling water balance. Urea is freely filtered, about 50% is reabsorbed in the proximal tubule. An amount equal to that reabsorbed is then secreted back into the loop of Henle. DCT and CT are impermeable to urea, therefore, no urea is absorbed here Finally, about half is reabsorbed again in the medullary collecting duct. The net result is that about half the filtered load is excreted. ADH increases urea permeability of CT in the medulla.

Tubular Reabsorption – Urea & Cl-

Phosphate – Calcium - Magnesium Renal threshold of PO4-3 and Ca2+ is their normal plasma concentration. 85% of filtered Phosphate is actively reabsorbed in PCT by Na+ - PO4 co-transport carrier. 15% filtered load is excreted in urine. 60% of plasma Ca2+ is filtered in the glomerular capillaries PCT and thick ascending limb of Loop of Henle reabsorb more than 90% of filtered Ca2+ DCT and CT reabsorb 8% of filtered Ca2+ Ideally the renal threshold for Glucose should have been 375 mg/100ml but it is not so. Why?

Phosphate – Calcium - Magnesium PO4-3 and Ca2+ are regulated by hormone parathyroid. PTH (parathyroid hormone) – causes Ca2+ reabsorption and inhibits phosphate reabsorption. PTH causes phosphaturia (increase phosphate in urine). Mg2+ is reabsorbed in PCT, thick ascending limb of loop of Henle and DCT Ideally the renal threshold for Glucose should have been 375 mg/100ml but it is not so. Why?

Other waste Products Other waste products e.g. uric acid, creatinine, phenol (derived from many foods) are not passively reabsorbed as urea. Urea is smallest particle of waste products, therefore, it is only waste product i.e. passively reabsorbed (50%) in PCT. Ideally the renal threshold for Glucose should have been 375 mg/100ml but it is not so. Why?

Obligatory Urine Volume It is the minimum quantity of urine that must be excreted each day to rid the body of waste products of metabolism and ions that are ingested. Obligatory urine volume is dependent on the maximum concentrating ability of the kidney. A normal 70-kilogram human must excrete about 600 milliosmoles of solute each day. If maximal urine concentrating ability is 1200 mOsm/L, the minimal volume of urine that must be excreted, called the obligatory urine volume, can be calculated as: 600 mOsm/day = 0.5 L/day 1200 mOsm/L Ideally the renal threshold for Glucose should have been 375 mg/100ml but it is not so. Why?

References Human physiology by Lauralee Sherwood, 8th edition Text Book Of Physiology by Guyton & Hall, 11th edition Review of Medical Physiology by Ganong. 24th edition

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