7.1 Renal regulation of water and acid-base balance Flashcards
- different renal processes regulating water balance - role of vasopressin in urine production and excretion - the role of kidney in maintaining the body's acid base balance - different renal-regulation associated clinical disorders
What the simplified version of the henserson-hasselbalch equation?
[H+] = (24*PCO2)/[HCO3-]
Where are the osmoreceptors?
Hypothalamus
What are the 5 functions of the kidney?
excretion of metabolic products e.g. urea
excretion of foreign substances e.g. drugs
homeostasis of body fluids, electrolytes & acid base balance
regulates blood pressure
secretes hormones (erythropoietin, renin)
What are the 3 types of passive transport that take place in the kidney?
diffusion
osmosis
electrical gradient difference
What are the 2 types of passive transport that take place in the kidney?
primary active (ATPase pump, endocytosis) secondary active (symport, antiport)
What is secondary active transport?
Movement of one solute along its electrochemical gradient which provides energy for the other solute to move against it
How is osmolarity calculated?
concentration x number of dissociated particles
mOsm/L
e.g. 100mmol/ L of NaCl
= 100 x 2
= 200 mOsm/L
Calculate the osmolarity for 100 mmol/L of glucose
100 mOsm/L
What % of your body weight is total fluid volume?
60%
What are the two main fluid compartments, what % of your total fluid volume are they?
extracellular fluid 33%
intracellular fluid 66%
What is the extracellular fluid made of?
25% - intravascular (plasma)
75% - extravascular (95% interstitial fluid, 5% transcellular fluid)
What is an example of transcellular fluid?
CSF
What are the two types of water loss?
unregulated
regulated
What are some examples of unregulated water loss? (4)
sweat
feces
vomit
water evaporation from respiratory lining and skin
What is regulated water loss?
renal regulation - urine production
What are the two types of water balance?
positive water balance
negative water balance
What positive water balance?
high water intake
increases the ECF volume
decreases Na+
decreases osmolarity
How do the kidneys correct positive water balance?
hyperosmotic urine (compared to plasma)
What is negative water balance?
low water balance
this causes ECF volume to decrease
increasing the concentration of Na+
increasing osmolarity
How do the kidneys correct negative water balance?
hyperosmotic urine production (compared to plasma)
and trigger thirst
Where is most water reabsorbed in the kidney?
PCT (~67%)
What % of water is reabsorbed in the loop of Henle?
15%
What is reabsorbed in the ascending limb of the loop of Henle?
NaCl
How is NaCl reabsorbed in the ascending limb of the loop of henle?
thin: passively
thick: actively
What happens in the descending limb of the loop of henle?
water is passively reabsorbed
Why is it significant that water is reabsorbed passively?
a gradient is therefore required so,
the medullary interstitium needs to be hyperosmotic
Why is NaCl transported into an out of in the loop of henle?
to maintain the so the medullary interstitium is hyperosmotic so more water reabsorption can occur
How much water is reabsorbed in the PCT and collecting duct?
variable depending of the body’s need and activation of the aquaporin 2 channels activated by vasopressin
Why is water passively reabsorbed?
so the body does not have to spend a lot of energy
What does counter current multiplication do in the kidneys?
highest osmolarity at bottom of loop of henle;
maintains gradient so water can move out of urine by osmosis
What is the vasa recta?
series of capillaries around the nephron, supply blood to the medulla
What transporter facilitate the recycling of urea out from the collecting duct into the medullary interstitium
UT-A1
UT-A3
What is the concentration of urea in the medullary interstitim
up to 600 mmol/L
What membrane does the UT-A1 transporter allow urea to cross?
apical cell membrane of collecting duct
What membrane does the UT-A3 transporter allow urea to cross?
basolateral cell membrane
Once urea has reached the medullary interstitium, what are the two places it can go?
Vasa recta
Thin descending limb
What transporter facilitates the movement of urea from the medullary interstitium into the vasa recta?
UT-B1
What transporter facilitates the movement of urea from the medullary interstitium into the thin descending limb?
UT-A2
What is the purpose of urea recycling from the collecting duct into the thin descending limb?
to increase the osmolarity of the interstitium
Urea recycling causes an increase in the osmolarity of the interstitium, what two purposes does this serve?
urine concentration occurs
urea excretion requires less water
How does urea recycling mean that urea excretion requires less water?
is the concentration of urea outside the collecting duct is high (up to 600 mmol/L) then the concentration of urea excreted in the urine can also be this high, meaning less water will have to be dragged along with it
Which urea transporters does vasopressin increase the expression of?
UT-A1
UT-A3
–> remember increases the concentration of urine
When intravenous fluids are given, what is the first fluid compartment it enters?
extracellular fluid compartment
Which compound, NaCl or Urea is responsible for generating a hyperosmotic medullary interstitium?
both
What type of hormone is vasopressin?
peptide hormone (9 aa)
Where is vasopressin produced?
Hypothalamus, from neurones in supraoptic and paraventricular nuclei
Where is vasopressin stored?
posterior pituitary
What is the primary function of vasopressin?
promotes water reabsorption from the collecting duct
What would a high plasma osmolarity cause in terms of ADH?
stimulate ADH production and release
opens up aquaporin channels
What would happen if plasma osmolarity decreased?
inhibition of ADH production and release
What is hypovolemia?
decreased volume of circulating blood in the body
What % change of circulating blood volume is required for stimulation/inhibition of ADH receptors?
5-10%
What receptors detect the change in circulating blood volume?
baroreceptors
What are the 5 factors that stimulate ADH production and release?
increased plasma osmolarity hypovolaemia (low blood pressure) nausea angiotensin II nicotine
What are the 4 factors that inhibition ADH production and release?
decreased plasma osmolarity
hypervolaemia (high blood pressure)
ethanol
atrial natriuretic peptide
describe the mechanism of action of ADH?
- ADH binds to the V2 receptors on the basolateral membrane of a principle cell
- This triggers a G protein mediated signalling cascade
- This activates protein kinase A
- Which increases the secretion of aquaporin-2 channels
- These AP2 channels are transported to and inserted in the apical membrane
- Through these channels allow more water to be reabsorbed by thr PCT
What AQP receptors can ADH increase and decrease as required?
AQP2 on the apical membrane
AQP3 on the basolateral membrane
Explain Na+ reabsorption into the blood in the thick ascending limb
Na - K ATPase pump (pumps out Na into the blood)
Low conc. of Na+ in the cell
Na+ K 2Cl symporter, transports sodium into the cell down its gradient.
This releases energy used to transports K and Cl into the cell
K and Cl are then transported into the blood by the K and Cl symporter
K used by Na - K ATPase pump to transport Na into the blood
In terms of osmolarity, when urine enters the descending limb it is..
isosmotic
In terms of osmolarity, when urine enters the descending limb it is..
hypoosmotic
What substances move in out out in the DCT?
Na - active
Cl - active
What substances move in or out in the collecting duct?
Na Cl (active) - outer medulla Water - inner medulla
What osmolarity is urine?
50 mOsm/L
What osmolarity is plasma?
~ 300 mOsm/L
What is antidiuresis?
concentrated urine in low volume excretion
What happens in antidiuresis?
ADH –> high
ADH supports Na reabsorption in:
- Thick ascending limb: Na+-K+-2Cl-
- Distal Convoluted tubule: Na+ - Cl- symporter
- Collecting duct: Na+ channel
by increasing the number of symporters and channels
What happens to water reabsorbtion in anti-diuresis?
DCT - water reabsorption
CD- water reabsorption in inner and outer medulla
What could the osmolarity of urine be in anti-diuresis
1200 mOsm/L
What are 3 ADH related clinical disorders?
- central diabetes insipidus
- syndrome of inappropriate ADH secretion (SIADH)
- nephrogenic diabetes insipidus
What is the cause of central diabetes insipidus?
decreased/negligent production and release of ADH
What is the cause of SIADH?
increased production and release of ADH
What is the cause of nephrogenic diabetes insipidus?
less/mutant AQP2
mutant V2 receptor
(normal amount of ADH produced)
What are the clinical features of central diabetes insipidus?
polyuria
polydipsia
What are the clinical features of SIADH?
hyperosmolar urine
hypervolaemia
hyponatraemia
What are the clinical features of nephrogenic diabetes insipidus?
polyuria
polydipsia
What is the treatment for central diabetes insipidus?
external ADH
What is the treatment for SIADH?
non-peptide inhibitor of ADH receptor
conivaptan & tolvaptan
What is the treatment for nephrogenic diabetes insipidus?
thiazide diuretics and NSAIDs
What do thiazide diuretics do?
reduce filtration rate at bowman’s capsule so less urine produced
Does ADH regulate the number of aquaporin channels on the apical or basolateral membrane?
both
What will the blood be in SIADH?
hypoosmotic - as holding onto a lot of water when it doesnt need to
What will the blood be in SIADH?
hypoosmotic - as holding onto a lot of water when it doesnt need to
What two things introduce acids and bases into our body?
diet
metabolism
What is the primary was bases are excreted from the body?
faeces
Because most of the bases are removed in faeces, what does this leave us with
net addition of metabolic acid
Why is it important to remove this net addition of metabolic acid?
so it does not affect the blood pH
What is the primary way metabolic acids are neutralised?
bicarbonate buffer system
What is the problem with the bicarbonate buffer system?
if it isnt replenished it will run out.
What is the role of the kidneys in metabolic acid neutralisation?
secretion and excretion of H+
reabsorption of HCO3- (almost 100%)
production of new HCO3-
What is the equation showing the bicarbonate ion as a buffer?
carbon dioxide + water <–carbonic anhydrase–> H+ + bicarbonate (HCO3-)
What organs manage the bicarbonate buffer system?
lungs
kidney
What happens to H+ if PCO2 increases?
[H+] also increases
If changes in H+ are caused by fluctuations in PCO2, what type of acid base disorder is it?
respiratory
If changes in H+ are caused by fluctuations in [HCO3-] , what type of acid base disorder is it?
metabolic
Where is most bicarbonate ions reabsorbed ?
PCT
What are the two ways the H+ ion can exit the cell and enter the tubular fluid?
Na+ H+ antiporter
H+ ATPase pump
How is bicarbonate reabsorbed into the blood in the PCT?
Na+ HCO3- symporter
Where are the intercalating cells?
DCT and collecting duct
What are the two types of intercalated cells?
a and b
What is the function of the a intercalated cell?
HCO3- reabsorption
H+ secretion
What is the function of the b intercalated cell?
HCO3- secretion
H+ reabsorption
Which intercalated cell is more commonly used?
a, for reabsorption of bicarbonate
b is used if body is getting alkali
What transporter is used to move HCO3- ions out of the intercalated cell into the blood (a), or tubular fluid (b)
Cl-HCO3- antiporter
Why do we have two types of intercalated cells?
to manage the acid base balance in the body
Where are new bicarbonate ions produced?
PCT
What molecule is bicarbonate created from in the PCT, and what other products are made?
Glutamine –> 2ammonium + 2 bicarbonate
When bicarbonate is produced in the PCT, why is it important that the ammonium is removed and not sent to the liver?
In the liver it will become 2 urea and a proton which will require neutralisation by a bicarbonate ion, nullifying its production
What is done with the ammonium byproduct in the PCT?
excreted in the urine
What are the two ways in which ammonium is removed from the cells in the PCT and into the tubular fluid?
Na+ H+ antiporter (with NH4+ ion substituting with H+) become ammonia (NH3) gas and diffuse out into the tubular fluid where it will bind with an H+ and become NH4+
How is bicarbonate produced in the DCT and collecting duct.
In the a intercalated cells,
when H+ is transported into the tubular fluid, instead of being neutralised by a bicarbonate, it can be neutralised by a phosphate ion (phosphate buffer system) so the bicarbonate made in the cell and enters the blood is a net gain
What are the four acid base imbalances?
metabolic acidosis
metabolic alkalosis
respiratory acidosis
respiratory alkalosis
What are the characteristics of metabolic acidosis?
low [HCO3-], low pH
What are the characteristics of metabolic alkalosis?
increased [HCO3-]
increased pH
What are the characteristics of respiratory acidosis?
increased pCO2
decreased pH
What are the characteristics of respiratory alkalosis?
decreased pCO2
increased pH
What is the compensatory response for metabolic acidosis?
increased ventilation
increased [HCO3-] reabsorption and production
What affect does hyperventilation have on PCO2?
hyperventilation = decreased PCO2
What is the compensatory response for metabolic alkalosis?
decreased ventilation
increase [HCO3-] excretion
What is the compensatory response for respiratory acidosis?
acute: intracellular buffering (so inc. CO2 enters the cells and gets turned into H+ and HCO3- by carbonic anhydrase, H+ neutralised by cell proteins so net +1 bicarbonate)
chronic: increased [HCO3-] reabsorption and production, increased excretion of H+ and NH4+
What is the compensatory response for respiratory alkalosis?
acute: intracellular buffering (shift equation to more carbonic acid side, so less bicarbonate produced)
chronic: decreased [HCO3-] reabsorption and production
pH= 7.2 [HCO3-] = 17mEq/L pco2 = 35mmHg
metabolic acidosis
pH=7.5, [HCO3-] = 17mEq/L, PCO2= 35mmHg
respiratory alkalosis
What is normal range of [HCO3-]?
23-30 mEq/L (24)
What is normal range of PCO2?
35 to 45 mmHg
4.7 - 6.0 kPa
