BISC 307L 1st Edition Lecture 37 Current Lecture Transport and Excretion Reabsorption of Na glucose HCO3 etc o o Already talked about Na going across the apical membrane Na H antiport 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 membrane To make this work must get rid of bicarbonate leaves through basolateral membrane there is a Na 3bicarbonate symport which is driven by the bicarbonate gradient and pumps 3 bicarbonates and 1 Na ion out of cell Filtered bicarbonate not used up because it gets reabsorbed by the ECF This is a mechanism for the reabsorption of Na and HCO3because it is a 3 Bicarbonate Na symport it is electrogenic and makes the membrane more negative o Some 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 acidic o The 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 membranes o Urea 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 gradient o Not 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 urine Secretion of H ions o o H ions are constantly excreted by 3 mechanisms 1 Proton secretion in proximal tubule previous slide sodium dependent 2 Distal tubule and collecting duct 2 Sodium independent proton 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 out 3 ATPase H K ATPase protons out and K in Protons come from same place as above dissociation of water and also pumps K ions in which leave the cell through K channels in basolateral membrane Mechanism for K reabsorption gets rid of acid by reabsorption of potassium acidosis associated with hyperkalemia Fate of Secreted H Ions o o If there were no buffers then up to a point these mechanisms would work but then halt because cant concentrate any more o Buffers Take up protons and convert them to something else renewing proton gradient 1 Bicarbonate buffer CO2 produced is reabsorbed into epithelial cell 2 Phosphate buffer K combining with dibasic Na phosphate can accept a proton to become monobasic and releases a Na ion which gets reabsorbed 3 Ammonia diffuse into tubular fluid and combines with protons to form ammonium ion which makes it impermeable and traps the protons in the urine K homeostasis o o o o o Need to keep K level in body constant K is most abundant cation in the body Inside concentration high and outside concentration not as high Where is most of the K located Most in skeletal muscle RBC liver bone Most K is contained in the cells and only 1 2 is located extracellular o We 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 stools o These 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 compartments o The liver and skeletal muscle are the two most important muscle in doing this o This 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 Xenobiotics o o For 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 secretion o Principle 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 EXAM o This K channel is called the ROMK1 renal outer medulla K channel o 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 thing Anionic diuretics Cationic nicotine Excretion and Clearance o o We rely upon the kidney to clear things from the blood o It is possible to measure the rate at which things get excreted from the body and measure glomerular filtration rate o To measure this need a substance that is freely filtered but not reabsorbeduse INULIN o INULIN is a polymer of fructose and non toxic and is freely filtered into the kidney tubule but not reabsorbed or secreted o Because 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 minute o By measuring the clearance of inulin in the blood you can measure the glomerular filtration rate Renal Handling of Solutes o o Once you have measured the GFR you can compare this will rate excretion of other substances o This will give you an idea of how other substances are handled by the kidney Micturition Reflex o o Bladder can hold 500ml of urine highly compliant o Two sphincter internal smooth muscle and external skeletal muscle innervated by spinal motor neurons o Urination is under reflexive control o 1 Stretch sensitive nerves excite parasympathetic neurons which stimulate contraction of bladder muscle and also inhibit motor neurons that are constricting the external sphincter o 3 Contractions increase with stretch sensitive sensors and force internal sphincter