Transport and ExcretionReabsorption of Na+, glucose HCO3- etcAlready talked about Na+ going across the apical membrane (Na+/H+ anti-port main way) meaning that the protons must go into the lumen- where are they coming from?Protons that are pumped into the lumen combined with bicarbonate ions (filtered) to make carbonic acid which dissociates to CO2 and H2O. Co2 permeable so easily permeates through the apical and basolateral membrane so there is always Co2 coming our. In the epithelial cell some CO2 enters where it combines with water which forms carbonic acid to forms protons and bicarbonate- it is these protons that provide the protons being pumped across the apical membraneFiltered bicarbonate not used up because it gets reabsorbed by the ECFThis is a mechanism for the reabsorption of Na+ and HCO3- because it is a 3 Bicarbonate Na+ symport it is electrogenic and makes the membrane more negativeSome of the H+ does not combine with bicarbonate so it is excreted in urine (way more protons are being secreted(excreted) than being reabsorbed)- our diets are acidicThe water ill follow by osmosis and things that are not transported will build up in concentration such as (Cl-) which creates a concentration gradient for Cl- to move across the epithelium- 2/3 paracellular route (between cells) and 1/3 goes through Cl- ion channels in both membranesUrea is concentrated in tubule fluid and in the proximal tubule and distal tubule, urea isn’t permeable so as water is reabsorbed then the urea is left behind and the concentration goes up and in those places that do have urea transporters (collecting duct) it will passively be reabsorbed down its concentration gradientNot much protein is taken up but once inside the cell they are degraded or put back across the basolateral side. This means there should be no protein in urineSecretion of H+ ionsH+ ions are constantly excreted by 3 mechanisms1. Proton secretion in proximal tubule (previous slide)sodium dependent2. Distal tubule and collecting duct2. Sodium independentproton pump in apical membrane pumping H+ out by H2O dissociation in cell and the hydroxyl ions combine with CO2 to form HCO3 and is pumped out through a Cl-/HCO3 exchanger and Cl- doesn’t accumulate and is pumped right out3. ATPase – H+/K+ ATPaseprotons out and K+ inProtons come from same place as above (dissociation of water) and also pumps K+ ions in which leave the cell through K+ channels in basolateral membraneMechanism for K+ reabsorption“gets rid of acid by reabsorption of potassium” – acidosis associated with hyperkalemiaFate of Secreted H+ IonsIf there were no buffers, then up to a point these mechanisms would work but then halt because cant concentrate any moreBuffersTake up protons and convert them to something else renewing proton gradient1. Bicarbonate bufferCO2 produced is reabsorbed into epithelial cell2. Phosphate bufferK= combining with dibasic Na+ phosphate can accept a proton to become monobasic and releases a Na+ ion which gets reabsorbed3. Ammoniadiffuse into tubular fluid and combines with protons to form ammonium ion which makes it impermeable and traps the protons in the urineK+ homeostasisNeed to keep K+ level in body constantK+ is most abundant cation in the bodyInside concentration high and outside concentration not as highWhere is most of the K+ located?Most in skeletal muscleRBCliverboneMost K+ is contained in the cells and only 1-2% is located extracellularWe take in about 100 mEq/day which is more than we need so excrete as much as we intakeget rid of about 100mEq/day and 90% done in kidney and 10% in stoolsThese are slow mechanisms so what is the buffer that handles it in the mean time? THE NA+/K+ PUMP!! This sequesters K+ into the intracellular compartmentsThe liver and skeletal muscle are the two most important muscle in doing thisThis happens by most of the K+ that is filtered is reabsorbed in the proximal tubulethen distal and collecting duct do the rest of the adjustment (distal tubule fine tuning due to principle cells and intercalating cells that regulate K+ reabsorption)Secretion of K+ Ions and XenobioticsFor the cell to secrete K+ it depends on where the channels are- if in basolateral membrane wont secrete but if in apical membrane then K+/Na+ pumps will drive secretionPrinciple cells: have Na+/K+ pumps in the basolateral membrane and K+ pumps in the apical membrane that is inwardly rectifying WHY DOES THIS MAKE SENSE-EXAMThis K+ channel is called the ROMK1 (renal outer medulla K+ channel)Mechanisms for secretion of xenobiotics:Foreign organic molecule that the kidney can secrete (drug or toxin)Kidney has broad capacity to secrete organic molecules and do this by a family of OAT and OCT that occur in both membranes and can transport xenobiotics to be excreted. Broad specificity. Same ones that are in liver cells to do the same thingAnionic: diureticsCationic: nicotineExcretion and ClearanceWe rely upon the kidney to clear things from the bloodIt is possible to measure the rate at which things get excreted from the body and measure glomerular filtration rateTo measure this need a substance that is freely filtered but not reabsorbed- use INULININULIN is a polymer of fructose and non toxic and is freely filtered into the kidney tubule but not reabsorbed or secretedBecause of this if you inject inulin in the blood, the amount of inulin appearing in the urine/min is the same as the amount being excreted/minuteBy measuring the clearance of inulin in the blood you can measure the glomerular filtration rateRenal Handling of SolutesOnce you have measured the GFR you can compare this will rate excretion of other substancesThis will give you an idea of how other substances are handled by the kidneyMicturition ReflexBladder can hold 500ml of urine- highly compliantTwo sphincter- internal (smooth muscle) and external (skeletal muscle innervated by spinal motor neurons)Urination is under reflexive control1. Stretch sensitive nerves excite parasympathetic neurons which stimulate contraction of bladder muscle and also inhibit motor neurons that are constricting the external sphincter3. Contractions increase with stretch sensitive sensors and force internal sphincter open causing urinationThis is a reflex that is suppressed through voluntary meansWater and Salt BalanceResponse to Changes in Blood volume and PressureOn a typical day we ingest about 2L of food and drinkWe need to keep total salt content and water content