Kidney - Secretion and pH Flashcards
1
Q
Secretion with neg charged ion
A
- occurs in cells in the proximal tubule
- Have organic ion transporters (OA-) which usually take organic ions that have negative charge but could also secrete organic ions with positive charge (O+)
- These are antiporters so take OA- out of cell into lumen and take neg ion out of lumen and into cell
- Bile salts are transported that have negative charge
- Liver when it metabolizes organic ions it generates these organic ions and puts a charge on them, usually a neg charge and then gives ability for kidney to kick it out
- In pharmacology this gets to be a big deal ; this happens in proximal tubule so before loop of henle
- Bile salts, aspirin, penicillin are the organic ions that are going into the cells and then out into lumen of proximal tubule cells
- Lot of competition for this transporter that is organic ion transporter
2
Q
PAH and secretion with positively charged ion
A
- Compound called PAH- which is para-amino hippuric acid ; at beginning of WWII there was penicillin – if give penicillin and PAH- at same time since then they compete for transporter and that extends half life of penicillin significantly so people can give doses of penicillin that less but can spread out its use by creating this competition
- Also have pathway for positively charged organic ion – things that compete for this transporter are: cimetidine (histimineantagonist) – given for gastric problems and ulcers to block acid secretion; drug called procainamide (cardiac drug that helps with arrhythmia)
- Want to know meds people on because if on both of these drugs then half life of both gets extended and so need to lower the dose for one or the other or both
3
Q
K+ Secretion in Distal Tubule
A
- we want to put K+ out into lumen and then to urine
- K+ ion channel is on lumen side of distal tubule
- contrast w/proximal tubule cell where K+ simply recycles back into the blood - b/c we’re more concerned w/moving Na+ into blood
4
Q
how does the kidney handle individual solutes?
A
- filtered glucose in Bowman’s capsule
- the more glucose in blood, the more gets filtered
- we reabsorb glucose in the proximal tubule to a particular point (max state/transport maximum, b/c only so many transporters)
- but at Tm there’s still more glucose so it shows up in the urine since all transporters are busy
- in normal individual the urine and filtered load curves are parallel
- once you hit glucose mx then you excrete glucose in urine and differential is what you transport back in
- at 1 mg/mL glucose you absorb all of the glucose
- if BG is far out then filter out a lot but you absorb lots of glucose and still glucose is filling up in urine
5
Q
Glucose and Urine
A
- filtered load (what gets filtered in glomerulus ) = [plasma in mg/ml] x GFR (120 mls/min)
- Tm = filtered load - excretion rate (what ends up in urine)
- excretion rate = urine vol x [urine]
- Filter, then in proximal tubule we reabsorb and some other substances can be secreted
- Graph – if increase plasma glucose you increase what is filtered; you reabsorb glucose, all of it normally and when exceed transport maximum, glucose shows up in urine
- Normally no glucose in urine so 0 mg/ml and vol is 1 ml/min but zero glucose in urine so in L part of graph and when substract you get positive number so its reabsorption and reabsorb 120 mg/min
6
Q
Diabetic
A
- Diabetic – high blood sugar so 5x normal; 5 mg/ml x 120 mls/min gives filtered load of 600 mg/min and minus excretion rate which is 225 mg/min assuming 2 ml/min urine and concentration of glucose in urine is 112.5 mg/ml and you get 225 as excretion rate
- Exceed transport max so 375 is transport max
- But under normal circumstances you can’t figure out transport max but can figure out if things are reabsorbed or secreted
- If blood glucose was 5 to 6 to 7 you increase filtered load and amount in urine goes up but diff btwn 2 remains the same and you get 375 again so same transport max
- Get 600 mg/ml in tubule and 225 mg/ml show up in urine and diff gives +375 mg/min which is reabsorption amount based on how much goes into urine
7
Q
Tm and Reabsorption or Secretion
A
- to figure out transport max you must have some spill over into urine
- if Tm is positive then you have reabsorption
- if Tm is negative then you have secretion
8
Q
PAH, which is secreted
A
- in urine you see what you filtered, plus what you secreted!!
- again curves are parallel, different is what you transport out!
- if increase PAH in blood then more in tubule,
- if more in urine then what you filtered –> it was secreted
- If less in urine then what you filtered –> it was reabsorbed
- Tm = filtered load - excretion rate
- if PAH is secreted then excretion rate is greater than filtered load
- so Tm will be neg which means secretion
9
Q
How did we figure out GFR = 120 mls/min?
A
- clearance of substance that is filtered and so not secreted and not reabsorbed
- clearance of a substance = excretion rate/[plasma]
- look at plasma clearance - ability of kidney to completely remove a solute from the plasma (mls/min)
- this can be used to figure out GFR only if the substance/solute is neighter secreted nor reabsorbed
- clearance x plasma concentration = urine concentration x urine vol
- clearance = urine conc x urine vol/plasma concentration
- clearance of insulin was used to determine GFR
- clearance of creatinine is about GFR in humans; take blood level of creatinine (breakdown product of creatine) and measure what is going on in urine to figure out GFR
10
Q
Insulin clearance gives you GRF
A
- insulin used to determine GFR - filtered only, not secreted or reabsorbed
- insulin clearance = GFR = 60 mg/ml x 4 ml/min / 2mg/ml
- Ci = 120 ml/min
- in humans to check kidney function we look at clearance of creatinine (creatine (product of muscle metabolism) to creatinine in liver)
- creatinine isn’t reabsorbed or secreted
11
Q
with plasma load, filtered load and urine which we can measure we can figure out reabs or secretion
A
- measure what is in urine to get excretion rate and diff between that and plasma load going into kidney to get reabsorb or secretion
- glucose “normal” : 700 ml/min x 1 mg/ml = 700 mg/min
- 120 mg/min = filtered load ; not in urine, so 120 mg/min reabsorbed
- “diabetic”: begin w/plasma glu of 5 mg/ml
- work thru and find glucose is spilled into urine (water follows the glucose)
- Tmax for glucose is 37.5 mg/min, and some glucose is cleared from blood (b/c in urine)
- can’t reabsorb all the glucose
12
Q
Glucose vs. PAH
A
glucose = reabsorbed solute
PAH = secreted
13
Q
PAH Clearance
A
- PAH clearance will give you renal plasma flow since it passes thru kidney via filtration and secretion
- 0.1 x 700 ml/min = 70 mg/min
- 0.1 x 120 = 12 mg/min = filtered load
- urine: 70 mg/min (clearance)
- secretion = 70-12 = 58 mg/min
- renal plasma flow is actually calculated using a secreted substance such as PAH
- because PAH actually gets completely cleared into urine, not all secreted solutes do
- what is in urine is bigger than what you filtered due to secreted stuff; diff between excretion and filtered gives neg number which is secretion
- only filter 20% of vol that goes thru so rest of blood in peritubular bed has PAH in it ans secrete that too
14
Q
Our pH
Why so tightly regulated
A
- our pH between 7.37 - 7.42 (low then go in acidosis, at 7 CNS not happy and go into coma, and above it you are alkaline/alkalosis/alkalemia and then at 7.7 you go tetany or convulsions)
- regulated due to proteins, NT, nervous system
- biggest challen to pH is production of acid - via normal metabolism
- CO2 = volatile acid, can blow off via respiratory system
- lactic acid
- phosphoric acid or ketone bodies
15
Q
What to do about acid?
A
- chemical buffering via proteins
- pKa = 7.4 for some proteins so COOH can donate H and NH2 can accept H
- histadine = really great a.a. for buffering w/imidizole group and alpha amino group
- HgB has 36 histadines - great buffer
- 75% of chemical buffering via proteins
- chemical buffering via phosphates: H2PO4 2- and HPO4- has pKa = 6.8
- chemical buffering via bicarbonate
- H2O + CO2 –> H2CO3 –> HCO3- + H+
- Henderson Hassalbach: pH = pKa + log [HCO3-]/[CO2]
- if we have 20:1 ratio of HCO3- to CO2 thn we can hit the7.4
- that’s why the body regulates this 20:1 ratio
HCo3- can be regulated by kidney and CO2 regulated by lungs
16
Q
Lungs - hyperventilating
A
- Graph 1: as you blow off CO2 you lose acid since decrease [Co2], so increase RMV will make blood more alkaline (less acidic)
- overtime, kidney compensates since decrease pH in blood, kidney increases HCO3- excretion into urine so overall decrease [HCO3-]
- diamax tends to inhibit rxn via inhibition of carboxylase anhydrase
- keep more CO2 in body so don’t blow off too much CO2 since not carried in blood as bicarbonate to be blown off
- Graph 2: if chemoreceptors detect decrease in pH, RMV increases in response (respiratory response to metabolic issue)
- it is difficult for the lungs to completely fix a metabolic issue - they try
- here chemorecetors respond to acid environment in blood so increase RMV and blow off CO2 which is acidic and help correct
18
Q
Kidney Regulation - HCO3- reabsorption in kidney
A
- HCO3 transport can be coupled w/Na+, or w/Cl- antiporter
- CO2 readily permeable to membrane
- CO2 in blood at equilibrium with CO2 in cell
- most CO2 in body transfered as bicarbonate
- if increase CO2 in blood, then increase HCO3- in blood - more CO2 diffuse into proximal tubule and push rxn to make more bicarbonate and increase bicarbonate in blood
19
Q
Kidney Regulation - H+ ion trapped to clear H+; NH4+ created which can leave via urine
A
- 60% of acid load exits this way
- H+ gets trapped on NH4+ (need pH 9 to get it off!)
- pH urine is from 4.4-8.0, usually on acidic end
- fates:
- H+ + HCO3-
- H+ +HPO4 2- –> H2PO4-: filtered phosphate, titratable acid
- ammonium ion traps NH3 + H+ –> NH4+ trapped once it gets on - its stuck
- 75% H+ come out via ammionium trap to eliminate
- pH has to reach 9.8 to get dissociation of NH4 and that will never happen
20
Q
Kidney Regulation - HPO3 2- filtered into lumen
A
- alpha intercollated cells in distal tubule
- aldosterone can stimulate H+ out of lumen
- HCO3 - goes into blood
- 40% of acid load exists this way
- if there is a lot of acid/CO2 in blood, this can happen
- you remove CO2, use H+ to make H2PO4 - (get rid of H+) and make new HCO3- to be put into blood
