Renal Function 3/25 What is nitrogenous waste and why must we remove it? What are the Structures of the glomerulus? What are the types of transport in nephron? What are the segmental differences along nephron? What is GFR and how does GFR change in disease? Why does a diabetic have an enormous urine volume and dehydration when the blood glucose it too high?

Overview of Renal Function: 1) You have two kidneys that clean your blood at very high metabolic cost in terms of % cardiac output and O 2 demand. 2) Blood wastes, especially toxic nitrogenous ones, are removed into glomerular filtrate by the kidneys. 3) Most of the valuable parts of the 180 L/day of filtrate created by the kidneys are reabsorbed by the nephron back into blood in the kidneys. 4) Hormones, such as ADH and aldosterone, fine tune this reabsorption process, in the collecting duct or distal nephron. 5) About 1% of the filtrate becomes urine that exits each kidney in a ureter and travels to the bladder for temporary storage and removal. 6) After the collecting duct, urine delivered to bladder and cannot be modified 6) Voiding the bladder causes urine to leave the body by the urethrawhen a combination of voluntary and involuntary nervous systems work together. Bonus: Kidney makes Angiotensin I that becomes Angiotensin II in lung via ACE Bonus: The kidney is critical for erythropoietin/Vit D production/Ca++ control. Bonus: The kidney also helps control blood pH and electrolyte levels.

What are nitrogenous wastes? Why does the kidney remove nitrogenous wastes from the body? Why is removal difficult? Relative safety/toxicity of metabolites: Carbos vs.Fats vs.Protein (AminoAcids) Amino acids metabolism releases toxic nitrogenous wastes when oxidized. Nitrogenous wastes: Ammonia- Urea (50%)- Uric acid- Creatinine- Relative water solubility of waste: Azotemia and severe exercise: Uremia and renal failure: How do we remove waste from the blood, but keep the vitamins, minerals, glucose, etc that we need in the blood?

What are the circulatory structures of the kidney? Why is the kidney so sensitive to ischemia and infarct? Cleaning the blood is VERY expensive in terms of ATP used for reabsorption, excretion, and secretion. Oxygen consumption as % of total= about 7% “AT REST” Cardiac output as % of total (at rest)= about 20% % Cardiac Output to kidney during exercise? 1-3% (minimal) What renal blood vessels deliver arterial blood to/return venous blood? Renal Arteries (Veins)- (Lt/Rt) Interlobar Arteries (Veins)- Arcutate and Interlobular Arteries (Veins)- Afferent Arteriole  (GlomerularCapillaries)  Efferent Arteriole –The efferent arteriole has three choices: it can perfuse…. –E.A.  Peritubular Capillaries- –E.A.  Vasa Recta-Capillaries- –E.A.  Back interlobular veins  Renal Veins  Vena Cava

Each kidney has a ONE renal artery in and ONE renal vein moving blood out. What happens if a thrombosis blocks an artery? ONE WAY IN (R.A.) ONE WAY OUT(R.V.)

THE NEPHRON IS THE FUNCTIONAL UNIT OF THE KIDNEY! WHAT DOES A NEPHRON DO? Major parts and players in the NEPHRON: Nephrons Filter then Reabsorb! Glomerular capillaries: site of blood filtration (about 180 Liters/day) Bowman’s Capsule around capillaries PCT (65% of reabsorption=most at start!) Loop of Henle (15-20% of reabsorption) Cortical LH or Medullary LH DCT (5-10% of filtrate of reabsorption) Collecting Ducts (0-10% of reabsorption) Fine tuning occurs when hormones act on CD! Technically CD is not part of nephron Filtrate Becomes Urine: 180 L filtrate/day reabsorpt.  18 L reabsorpt.  1.80 L reabsportion  900ml Urine/day Loop of H. Medulla

Each collecting duct receives filtrate (now called urine) from many distal convoluted tubules Glomerulus, PCT, Short Loops, and DCT Long Loops of Henle For Maximal Water Reabsorption! Urine passes into the ureters for delivery to trigone of the bladder

GLOMEROLAR (or “BOWMAN’S”) CAPSULE AND THE GLOMERULUS IS WHERE FILTRATION OCCURS. Arterial Supply of Renal Corpuscles (capillaries): Afferent Arteriole (IN) and Efferent Arteriole (OUT) Glomerular capillaries (corpuscles) in between Efferent Arterioles deliver some blood into a second set of capillaries (peritubular or vasa recta)…yes this is a portal system! Glomerular Capillaries are under high pressure These capillaries are rich in fenestrations (80nm wide) that allow selected materials in blood to pass through to capsular space (exit blood). Basement Membrane Fenestra (8 nm)- Podocytes and slits (Fenestra 30nm) Large proteins (negative charge) are excluded based on size and charge, everything else can pass fenestrations, please don’t forget that protein charge is very important! What happens to urine protein content if pores get too big?

The key to the glomerulus is having fenestra that are large enough to allow large amounts of fluid to be filtered, yet small enough so that cells and proteins are unable to be filtered! Plasma proteins are negatively charged and the sides of slits are negatively charged (this creates charge repulsion). It is also important to have supporting structures on the back side of the basement membrane to hold things in place (podocytes).

Lets consider the forces that create filtrate at the start of a glomerular capillary! Hydrostatic pressure in capillary= +60 mmHg out of capillary Hydrostatic pressure in capsule= -18 mmHg out of capillary(opposes60) Osmotic pressure in plasma= -28 mmHg into capillary Osmotic pressure in filtrate= 0 mmHg essentially zero! –Hopefully NO protein was filtered! Net Filtration Pressure: (+60out of blood)+(18into blood) + (-28into blood) + (0) = NET OUT mmHg (60mmHg-18mHg) - 28 mmHg = NET OUT mmHg 42mmHg – 28mmHg = +14 mmHg OUT! Therefore fluid is filtered from the start of the glomerular capillary, through the fenestrations, and into the glomerular capsule(“glomerular filtration”) Volume filtrate/Time = glomerular filtration “rate” (GFR) Blood is very viscous (“thick”) after leaving glomerular capillaries!

GLOMERULAR FILTRATION RATE (“GFR”) IS VOLUME OF FILTRATE PRODUCED/MINUTE (ml fluid entering capsule/minute) Facts: Kidney size(fist), location(retroperitoneal), number (2) Why do we clinically measure renal function (filtration rate)? Filtration is a function of hydrostatic pressures: blood pressure in capillary vs. hydrostatic pressure in capsule. It is also a function of oncotic pressure created by hydrogen-bonds of water to protein in the blood (protein “should” not be in filtrate). Typical GFR=120 ml/minute this is V.I.P. This is typically split by the two kidneys, if you lose one all 120 ml/minutes goes to the one remaining kidney. How much is this per day? 125 ml/min(60min/hr)(24hr/day)= 180,000ml/day What happens to GFR if bacteria infect the kidney and erode the slits (fenestrations)? What happens to GFR if the blood pressure is too high or low? What happens to GFR if the bladder can’t drain?

PROXIMAL CONVULUTED TUBULE IS THE FIRST PART OF THE NEPHRON TO RECLAIM VALUABLE SALTS AND WATER FROM THE FILTRATE THAT WAS JUST FORMED. 65% of water reabsorption occurs along the PCT! How Much Is This? (180L)(0.65) = 120 L (60 L left in filtrate) Tubular Epithelium: Luminal, Basolateral, Interstitial Tight Junctions- Na+/K+-ATPase pushes ions into interstitium Secondary Active Tx: Na+-Glucose Co-transport Solvent Drag pulls water into peritubular capillary Filtrate not to different from what it was at start except that volume is reduced 65% (120 L is now only 60L). Fluids and reabsorbed materials are then transferred to peritubular capillaries and whisked away to the renal vein.

The key to reabsorption in all parts of the nephron (and PCT) is that if you pump ions out of the filtrate, water will follow via solvent drag. Many pumps help make this possible.