L28-kidney lecture 3- urine PH and drug removal

what are the possible routes ( of excreation ) for substances entering the nephron

what is the renal processing of a substance based on

• to what degree is the substance filtered

• how much is reabsorbed

• how much is secreted

different factors affects these things

what does OATS stand for and what are they

organic anon transporters

• they are transporters that passively transport anionic substances down a concentration gradients

• they are important for the renal secretion of drugs and substances

where are OATS primarily expressed

( OAT1/3 , OATT4 , URAT1 )

in the proximal tubule

OAT1/3- basolateral ( blood→ tubule cell)

OAT4- apical ( tubule cell→ urine/inside of nephron)

URAT1- apical ( important for uric acid reabsorption )

what does OCTS stand and what do they do

organic cation transporters

• they passively transport cationic substances down concentration gradients

• theyre important for the excretion of many drugs and substances

where ate OCT primarily expressed

(OCT 2/3 , OCT1 , )

• OCT 2&3- Basolateral ( blood → tubule cell )

• OCT1 -primarily found in the liver but some are seen in the kidney

when substances are in the cell through OCTS how to thee leave into the tubule fluid

through the apical transport of MATE 1&2 which is an organic cation counter transporter

what is the key enzyme that regulates acid base homeostasis

carbonic anhydrase

describe how the Ph is lowered and raised and the kidneys role in this

• adding or subtracting bicarbonate lowers or raises H⁺ therefore influencing ph

• the kidney regulates bicarbonate HCO^-₃

• so it regulates ph

describe bicarbonate reabsorption in the Kidney

• inside the tubule cells there is carbonic anhydrase

• this means that the carbonic acid created can be broken down into H⁺ and HCO^- ₃

• the hydrogen ions are transported out of the tubule cells and into the tubule

• whilst the bicarbonate is transported from the tubule cells into the interstitial space then reabsorbed into the blood

• the hydrogen that’s been pumped into the tubule is able to react with filtered bicarbonate forming carbonic acid again

• which breaks down into water and carbon dioxide which is reabsorbed

• so there no net loss of bicarbonate

explain bicarbonate generation in the kidneys

• in the tubule cells there is carbonic anhydrase present

• this forms water and carbon dioxide into carbonic acid which is split into bicarbonate and hydrogen ions

• the hydrogen ions are pumped into the tubule whilst the bicarbonate are pumped into the blood

• the hydrogen now in the tubule is able to combine with filtered phosphate to form

• the product is then excreted

• this results in the gai of bicarbonate

describe how bicarbonate is generated through glutamine metabolism

• the amino acid glutamine enters the tubule cells through either the filtrate or the blood plasma

• it then gets broken down into ammonia and bicarbonate

• the ammonia gets pumped into the tubule then excreted

• the bicarbonate moves into the blood

• so there a net gain of bicarbonate

what is alkalosis and what is acidosis

• alkalosis- when the body loses hydrogen ions, the PH increases and becomes more alkali

• acidosis- when the body gains more hydrogen ions and the ph. decreases and becomes more acidic

explain the kidneys response to acidosis

• in acidosis there is a high number of protons in the tubule cells

• so they enter into the tubule and react with all the filtered bicarbonate and more of the filtered phosphate

• the kidney can also respond to acidosis to increase glutamine metabolism

• overall the body generates more bicarbonate ions which helps push the equation backwards decreasing hydrogen ions

what is the kidneys response to alkalosis

• there is little hydrogen ions inside the tubule cells

• so there are less hydrogen ions being passed into the tubule

• so less is there to combine with the bicarbonate in the filtrate- so less is reabsorbed

• and glutamine metabolism is lowered- so there is less generation of bicarbonate

• overall this pushes the equation to the side that increases bicarbonate and therefore increases hydrogen ions

explain what happens to drugs depending on if the urine is alkaline or acidic

• most drugs are either weak bases or weak acids

• in alkaline urine acidic drugs are ionised

• in acidic urine alkaline drugs are ionised

• ionised drugs are less likely to be reabsorbed in the kidney so there’s increased excretion