Uro Renal regulation of water and acid-base balance Flashcards
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
What is the distribution of body fluid: extracellular : intracellular?
Which compartment does fluid enter first?
1:2 extra:intra
Fluid enters ECF first the equilibrates with ICF
what makes up extracellular fluid?
Extravascular (75%)
- interstitial fluid (95%)
- transcellular fluid (5%) (inc. peritoneal fluid, csf and periocular fluid)
Intravascular (25%)
(plasma)
examples of sources of unregulated water loss
Sweat
Feces
Vomit
Water evaporation from respiratory lining and skin
Explain how renal regulation works when you have a positive water balance?
- High water intake
- Inc. ECF volume, Dec. [Na+], dec. osmolality
- Hypoosmotic urine production
- Osmolarity normalises
Why does the medullary interstitium need to be hyperosmotic?
Since water is reabsorbed through the passive process of osmosis, it requires a gradient.
-> hyperosmotic conditions allows for water reabsorption to occur from the Loop of Henle and Collecting duct.
What does UT-A2 facilitate?
urea entering the loop of henle (thin descending limb)
What does UT-A3 facilitate?
urea entering the medulla from collecting duct
which urea transporters does vasopressin boost?
UT-A1 & UT-A3 numbers (more urea in blood)
main function ADH?
Promote water reabsorption from collecting duct
Where is ADH produced?
: Hypothalamus (neurons in supraoptic & paraventricular nuclei)
Where is ADH sotred?
Posterior Pituitary
which receptors detect changes to plasma osmolality? Where are they found?
osmoreceptors in hypothalamus.
What does ADH up/down regulate?
AQP2 and AQP3 as required
is AQP2 on the apical/basolateral membrane?
apical
is AQP3 and 4 on the apical/basolateral membrane?
basolateral
Describe how NaCl reabsorption occurs in thick ascending limb ?
Na+-K+-2Cl- symporter pumps ions in (apical)
Na+-K+ ATPase pump 3Na+ out and 2k+ in (basolateral)
K+-Cl- symporter pumps ions out (basolateral)
Cl- passively moves through channel out on basolateral side
K+ passively moves out through channel on apical side and is recycled
Describe NaCl reabsorption at the DCT?
Na+-Cl- symporter pumps ions in (apical)
Na+-K+-ATPase pump pumps 3Na+ out and 2K+ in (Basolateral)
K+-Cl- symporter pumps ions out (basolateral)
Cl- passively moves out through channel (basolateral)
Describe how Na+ reabsorption occurs in the principal cells of the collecting duct
Na+ passively moves in through channel (Apical)
Na+-K+-ATPase pump pumps 3Na+ out and 2K+ in (basolateral)
ADH supports Na+ reabsorption in:
Thick ascending limb: ↑Na+ - K+ - 2Cl- symporter
Distal convoluted tubule: ↑Na+ - Cl- symporter
Collecting duct: ↑Na+ channel
cause of central diabetes insipidus?
Decreased/negligent production and release of ADH
cause central diabetes SIADH (Syndrome of inappropriate antidiuretic hormone secretion)?
Increased production and release of ADH
cause nephrogenic diabetes insipidus?
Less/mutant AQP2
Mutant V2 receptor
Clinical features central diabetes insipidus?
- polyuria
- polydipsia
clinical features SIADH?
Hyperosmolar urine
Hypervolemia
Hyponatremia
clinical features nephrogenic diabetes insipidus?
Polyuria
Polydipsia
Treatment central diabetes insipidus?
external ADH (ddAVP/ desmopressin)
Treatment SIADH?
Non-peptide inhibitor of ADH receptor
conivaptan & tolvaptan
Treatment nephrogenic diabetes insipidus?
thiazide diuretics + NSAIDS
roles of kidneys in acid-base balance?
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
why is there a net addition of metabolic acid from diet metabolism?
base excretion in faeces
⍺-Intercalated cell function
HCO3- reabsorption & H+ secretion.
This is via Cl- HCO3- antiporter
β-Intercalated cell function
HCO3- secretion & H+ reabsorption.
Secretion via Cl- HCO3- antiporter on apical membrane
Reabsorption via H+ ATPase pump
Give an example of regulated water loss?
Renal regulation- urine production
Explain how renal regulation works when you have a negative water balance?
- Low water intake
- Dec. ECF volume, Inc. [Na+], Inc. osmolality
- Hyperosmotic urine production
- Osmolarity normalises
Describe the process of countercurrent multiplication
This is the process by which the interstitial medulla becomes hyperosmolar and creates a conc. gradient.
As salt and water moves from the thick ascending loop into the interstitial medulla it inc. the osmolality causing water to move from the thin decending loop into the interstitial medulla to equilibrate
After this repeats several times a conc. gradient is achieved
What does UT-A1 fascilitate?
Urea moving from tubular fluid into collecting duct cells
What does UT-B1 fascilitate?
Urea moving into vasa recta (blood)
What is the mechanism of ADH?
ADH binds to V2 receptor which is coupled to a G protein
This activates adenylate cyclase which produces cAMP then protein kinase A
This leads to insertion of AQP2 on the apical membrane
This promotes reabsorption of water from the collecting duct into the blood via AQP3 and 4
Describe how diuresis occurs along the entire nephron
At the PCT: 67% water reabsorption, 67% NaCl reabsorption
TDL of LOH: Isosmotic fluid enters. Impermeable to NaCl. Water passively reabsorbed .
ThinAL of LOH: Impermeable to water. NaCl passively reabsorbed.
ThickAL of LOH: NaCl actively reabsorbed. Hypoosmotic fluid
DCT: NaCl actively reabsorbed. Impermeable to water (AQP 2 absent)
CT: Hypoosmotic fluid. NaCl actively reabsorbed. Water reabsorbed
Hypoosmolar and watery urine
How much bicarbonate is in the ECF and how do we maintain this amount?
ECF [HCO3-] = 350mEq or 24mEq/L
If we use this without replenishing it we would run out in 4-7 days and go into metabolic acidosis
What equation represents metabolic acid neutralisation?
H2SO4 + 2NaHCO3 -> Na2SO4 + 2CO2 + H20
HCl + NaHCO3 -> NaCl + CO2 + H2O
How much bicarbonate is reabsorbed around the nephron?
PCT: 80%
ThickAL of LOH: 10%
DCT: 6%
CT: 4%
What equations are is used to calculate pH and [H+] from [HCO3-] and PCO2?
pH = pK’ + log (HCO3-/aPCO2)
[H+] = (24 x PCO2)/[HCO3-]
How is HCO3- reabsorbed in the PCT?
H+ moved from cell into tubular fluid via Na+- H+ antiporter and via H+ ATPase pump
In tubular fluid: H+ + HCO3- -> H2O3- -> H20 + CO2 (via carbonic anhydrase)
CO2 enters cell by diffusion
In cell: H+ + HCO3- H20 + CO2 (via carbonic anhydrase)
On basolateral membrane: Na+- HCO3- symporter pumps bicarbonate into blood.
Na+/K+ ATPase also present
How is new bicarbonate made in the PCT?
On apical side: Na+- H+ antiporter secrets urea into tubular fluid
NH3- Passively moves out
Na+ - H+ antiporter secretes H+ into tubular fluid
In tubular fluid: H+ + NH3 -> NH4+ (urea)
In cell: Glutamine -> 2NH4+ (secreted)
Glutamine -> A2- -> 2HCO3- (reabsorbed)
How is new bicarbonate made in the DCT and CT?
On apical side: H+ ATPase pump secretes H+
H+ K+ ATPase secretes H+
In tubular fluid: H+ + HPO42- -> H2PO4- (phosphate buffer neutralises protons)
In cell: H+ + HCO3- H20 + CO2 (via carbonic anhydrase)
Basolateral side: Cl- - HCO3- antiporter (bicarbonate reabsorption) and Cl- channel
What is the compensatory mechanism for respiratory acidosis?
Intracellular buffering to inc. bicarbonate reabsorption and production
What is the compensatory mechanism for respiratory alkalosis?
Intracellular buffering to dec. bicarbonate reabsorption and production
