regulation of water and acid base balance Flashcards
what is osmolarity?
Osmotic pressure ∝ No. of solute particles
Osmolarity = Concentration x No. of dissociated particles
= Osm/L OR mOsm/L
Calculate the osmolarity for 100 mmol/L glucose and 100mmol/L NaCl.
Osmolarity for glucose = 100 x 1 = 100 mOsm/L
Osmolarity for NaCl = 100 x 2 = 200 mOsm/L
= 300 mOsm/L
water moves from an area of low to high osmolarity
what is water distribution around the body?
Total fluid volume = ~60% of body weight
2/3 in intercellular fluid
1/3 in extracellular fluid:
- 1/4 of this is in plasma (intravascular)
- 3/4 extravascular: 95% interstitial fluid, 5% transcellular (eg. CSF) fluid
what are the methods of water loss from the body?
unregulated: Sweat Feces Vomit Water evaporation from respiratory lining and skin
regulated:
urine
how does renal regulation work in terms of positive and negative water balance?
positive: high water intake -> increased ECF volume decreased sodium ion concentration decreased osmolarity -> hypoosmotic urine (dilute urine) -> osmolarity normalises
negative: low water intake -> decreased ECF volume increased sodium ion concentration increased osmolarity -> hyperosmotic urine -> osmolarity normalises
how does water reabsorbtion take place in the nephrons?
Since water is reabsorbed through the passive process of osmosis, it requires a gradient.
The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and Collecting duct.
67% of water is reabsorbed in the proximal convoluted tubule
15% in the thin descending limb of the loop of henle
here NaCl cannot leave, and water is reabsorbed passively
in the thin ascending limb NaCl leaves passively
water cannot be reabsorbed
in the thick ascending loop, NaCl is actively transported out
variable water is reabsorbed in the collecting duct, due to the effects of ADH
what is counter current multiplication?
look at the diagram, it explains it better
- active salt reabsorbtion from the thick ascending loop
increases the osmolarity in the interstitium - this causes passive water reabsorbtion from the thin descending loop
- due to salt not being able to be reabsorbed in the thin descending loop, osmolarity can only get so low, so it is highest at the bottom
- im not really sure
by the end, the osmolarity goes:
thin descending: 300 700 1000 1200
thin ascending:
1200
thick ascending: 1000 800 500 100
how does urea recycling work?
in the collecting duct of the kidney there are UT-A1 and UT-A3 channels that carry urea from the collecting duct into the interstitium
vasopressin increases the numbers of these channels
so water follows urea into the interstitium when you are running low on water, as osmolarity is increased
urea is either then:
taken back into the descending loop by UT-A2 channels
taken into the Vasa recta (blood) by UT-B1 channels
{urea excretion requires less water as:
urine concentration occurs}
idk she didnt really make sense
what is vasopressin?
aka ADH
Description: Protein (Length of 9 Amino acids)
Main function: Promote water reabsorption from collecting duct
also plays a role in sodium and urea reabsorbtion
Production: Hypothalamus (neurons in supraoptic & paraventricular nuclei)
storage: posterior pituitary
what stimulates and inhibits ADH production?
stimulatory: increased plasma osmolarity (as water leaves cells so they shrink and fire more) hypovolaemia decreased blood pressure nausea angiotensin 2 nicotine
inhibitory: decreased plasma osmolarity hypervolaemia increased blood pressure ethanol atrial natriuretic peptide
what is the mechanism of action of ADH?
ADH binds to V2 receptors on the basolateral side of the collecting duct
this activates a G protein coupled receptor
activates adenylate cyclase
atp-> cAMP
increases protein kinase A
more aquaporin 2 channels are inserted into the apical membrane
more aquaporin 3 channels are inserted into the basolateral side
water is reabsorbed from the lumen through these channels, AQP 2, then AQP 4
back into the blood
ADH up/downgrades AQP2 & AQP3 numbers as required.
how does urea recycling work?
in the collecting duct of the kidney there are UT-A1 and UT-A3 channels that carry urea from the collecting duct into the interstitium
vasopressin increases the numbers of these channels
so water follows urea into the interstitium when you are running low on water, as osmolarity is increased
urea is either then:
taken back into the descending loop by UT-A2 channels
taken into the Vasa recta (blood) by UT-B1 channels
{urea excretion requires less water as:
urine concentration occurs}
idk she didnt really make sense
what is vasopressin?
aka ADH
Description: Protein (Length of 9 Amino acids)
Main function: Promote water reabsorption from collecting duct
also plays a role in sodium and urea reabsorbtion
Production: Hypothalamus (neurons in supraoptic & paraventricular nuclei)
storage: posterior pituitary
what stimulates and inhibits ADH production?
stimulatory: increased plasma osmolarity (as water leaves cells so they shrink and fire more) hypovolaemia decreased blood pressure nausea angiotensin 2 nicotine
inhibitory: decreased plasma osmolarity hypervolaemia increased blood pressure ethanol atrial natriuretic peptide
what is the mechanism of action of ADH?
ADH binds to V2 receptors on the basolateral side of the collecting duct
this activates a G protein coupled receptor
activates adenylate cyclase
atp-> cAMP
increases protein kinase A
more aquaporin 2 channels are inserted into the apical membrane
more aquaporin 3 channels are inserted into the basolateral side
water is reabsorbed from the lumen through these channels, AQP 2, then AQP 4
back into the blood
ADH up/downgrades AQP2 & AQP3 numbers as required.
what is antidiuresis?
Concentrated urine in low volume excretion
ADH amount: High
ADH supports Na+ reabsorption in:
Thick ascending limb: ↑Na+ - K+ - 2Cl- symporter
Distal convoluted tubule: ↑Na+ - Cl- symporter
Collecting duct: ↑Na+ channel
increases osmolarity of interstitium, so more water reabsorbed
how is NaCl reabsorbed in the thick ascending limb?
active reabsorbtion
basolateral membrane:
Na-K-2Cl symporter
(K is recycled back out of the cell into the lumen)
apical membrane:
Na-K ATPase pump (sodium leaves, into blood. potassium back into cell)
K-Cl symporter into blood
also Cl channels into blood
main is Na+ - K+ - 2Cl- symporter
how is NaCl reabsorbed in the proximal convoluted tubule?
active process
basolateral membrane:
Na-Cl symporter (into cell from lumen)
apical membrane:
Na-K ATPase pump (3 sodium out into blood, 2 potassium, into cell)
K-Cl symporter into blood
Cl channels into blood
main is Na+ - Cl- symporter
how is Na+ reabsorbed in the principal cells of the collecting duct?
active process
basolateral membrane:
sodium ion channels
apical membrane:
sodium potassium ATPase (3 sodium out, 2 potassium)
main is Na+ channels
what is acid base balance and why is it done? and what are the roles of the kidneys in this?
diet + metabolism ->
acid + base
-> base excretion in faeces ->
ned addition of acid (50-100 mEq/day)
so we need metabolic acid neutralisation:
𝐻2𝑆𝑂𝟒+2𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎2𝑆𝑂4+2𝐶𝑂2+2𝐻2𝑂
𝐻𝐶𝑙+𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎𝐶𝑙+𝐶𝑂2+𝐻2𝑂
ECF [HCO3-] = ~350mEq OR 24mEq/L
role of the kidenys:
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
Cant rely solely on bicarbonate as it will run out in 7 days
So kidneys make new bicarbonate
Reabsorbs almost 100% of bicarbonate
what is central diabetes insipidus?
cause: Decreased/negligent production and release of ADH
clinical features:
Polyuria
Polydipsia
treatment:
external ADH
what is syndrome of inappropriate ADH secretion?
SIADH
cause:
Increased production and release of ADH
clinical features:
Hyperosmolar urine
Hypervolemia
Hyponatremia
treatment:
Non-peptide inhibitor of ADH receptor
(conivaptan & tolvaptan)
what is nephrogenic diabetes insipidus?
cause:
Less/mutant AQP2
Mutant V2 receptor
clinical features:
Polyuria
Polydipsia
treatment:
Thiazide diuretics + NSAIDs
(paradoxical effect but no one knows why)
what is acid base balance and why is it done?
diet + metabolism ->
acid + base
-> base excretion in faeces ->
ned addition of acid (50-100 mEq/day)
so we need
what is the role of bicarbonate as a buffer?
𝑪𝑶𝟐 + 𝑯𝟐𝑶 ↔ 𝑯𝟐𝑪𝑶𝟑 ↔ 𝑯+ + 𝑯𝑪𝑶𝟑−
first reaction uses carbonic anhydrase
80% of bicarb reabsorbtion takes place in the PCT
10% in the thick ascending limb
6% in the DCT
4% in the collecting duct
what is the henderson hasselbalch equation?
𝒑𝑯=𝒑𝑲^′+𝒍𝒐𝒈 (𝑯𝑪𝑶𝟑−)/𝜶𝑷𝑪𝑶𝟐
[𝑯+]= (𝟐𝟒 𝐱 𝑷𝑪𝑶𝟐)/([𝑯𝑪𝑶𝟑−])
changing pCO2 is respiratory alkalosis/acidosis
changing {HCO3-} is metabolic
how are bicarbonate ions reabsorbed?
HCO3 and H+ are produced from CO2 and water when CO2 enters the cell
PCT:
Na-HCO3 symporter (bicarb into the blood)
H+ ions are excreted using:
H+ ATPase pump
Na-H antiporter
DCT and collecting duct:
⍺-Intercalated cell: HCO3- reabsorption & H+ secretion.
β-Intercalated cell: HCO3- secretion & H+ reabsorption.
how is bicarb reabsorbed/secreted in the DCT and collecting duct?
⍺-Intercalated cell: HCO3- reabsorption & H+ secretion.
β-Intercalated cell: HCO3- secretion & H+ reabsorption.
alpha:
bicarb reabsorbed through Cl- - HCO3- antiporter
H+ secreted through H+ ATPase Pump
or H+ - K+ ATPase
beta:
bicarb excreted through Cl- - HCO3- antiporter
H+ reabsorbed through H+ ATPase pump
how are new bicarbonate ions produced?
PCT:
glutamine ->
2NH4+ and a 2- anion
2- anion -> 2 bicarbonate (leaves cell into blood)
the NH4+ leaves the cell as it would make 1 urea and an H+ with bicarbonate if it stayed
in tubular fluid NH3 + H+ -> NH4+ (ammonium, which is peed out)
DCT and collecting duct:
Cl- - HCO3- antiporter pumps bicarb back into the blood (bicarb from normal H2O CO2 reaction)
in the tubular lumen HPO4 2- is used as a buffer instead to create a net gain of bicarb
HPO4 2- + H+ -> H2PO4-
how does ventilation change acid base balance?
increased ventilation (hyper) corrects acidosis
decreased ventilation corrects alkalosis (more CO2 hanging about in the lungs)
