Renal regulation of water and acid-base balance Flashcards
What is osmotic pressure directly proportional to?
No of solute particles, not size
What is osmolarity?
Concentration x no of disassociated particles
=osm/l or mOsm/L
What is the total fluid volume ?
60% of body weight
How is the body fluid split between extracellular and intracellular
1/3 - extra cellular
How is extra cellular fluid split?
What are the two ways in which water can be lost ?
Unregulated and regulated
What are the ways water can be loss - unregulated
Sweat
Feces
Vomit
Water evaporation from respiratory lining and skin
What are the ways water be loss - regulated ?
Renal regulation – urine production
What are 2 types of renal regulation
Positive water balance and negative water balance
What is positive water balance ?
What is negative water balance?
Where is the water reabsorbed
2/3 in PCT, 15% in descending limb
What is countercurrent multiplication?
Step 1 - active salt reabsorption in thick ascending loop of Henle
Step 2 -passive water reabsorption in descending loop of Henle
What is the purpose of urea recycling*
To have urea concentration in the medulla interstitium
To get rid of urea with as little water as possible
Which side is UTA1?
Apical
Which side is UTA3?
Basolateral
What is vasa recta
Capillary network surrounding the nephron in the medullary region
What happens when urea enters the nephron via the thin descending limb?
Enters through UTA2 receptor
What is ADH and what is its main function
Protein of 9 amino acids
Promote water reabsorption from collecting duct
Other functions: helps with urea recycling an sodium reabsorption
Where is ADH produced
Hypothalamus (neutrons in supraoptic and paraventricular nuclei)
Where is ADH stored
Posterior pituitary
How is a fluctuation of plasma osmolarity detected
By osmoreceptors
What factors stimulate ADH production and release?
Increase in plasma osmolarity
Hypovolemia - decrease in blood pressure
Nausea
Angiotensin II
Nicotine
How is change in blood pressure detected and where are signals sent
By baroreceptors and sent to hypothalamus
What state does the medullary interstitium need to be in for water reabsorption to occur from the Loop of Henle and Collecting Duct?
Hyperosmotic
What state does the medullary interstitium need to be in for water reabsorption to occur from the Loop of Henle and Collecting Duct?
Hyperosmotic
What state does the medullary interstitium need to be in for water reabsorption to occur from the Loop of Henle and Collecting Duct?
Hyperosmotic
What is the purpose of urea recycling
To have urea concentration in the medulla interstitium to increase osmolality and support passive water reabsorption
To get rid of urea with as little water as possible
Where can urea go?
Through UT-A1 and UT-A3 tranporters
Then either to the vasa recta via UT-B1 transporters (into blood circulation)
Or back to the nephron through the descending limb via UT-A2 transporters
What happens when urine concentration hapens?
Urea excretion requires less water
How does vasopressin help urea recycling?
By boosting UT-A1 and UT-A3 numbers in colllecting duct
What factors inhibit ADH production and release?
Decrease in plasma osmolarity
Hypervolemia - increase in blood pressure
Ethanol
Atrial natriuretic peptide
How does NaCl reabsorption happen in the thick ascending limb?
What is the mechanism of ADH?
ADH reaches the principal cells, which are lining the collecting duct lumen, and the later part of the DCT - through the blood circulation
Attaches itself to the V2 receptor on the basolateral membrane of the principal cell
Binding reaction activates the G Protein coupled mediated signalling cascade
Activates Protein Kinase A
Secretion of AQP2 channels
These are transported the apical side membrane
Water can then enter the principal cells and then leave via either AQP3 or AQP4 to get into the blood
What is diuresis?
Increased Dilute Urine Excretion
What happens during diuresis?
ADH amount is small or zero
Isosmotic fluid enters Loop of Henle and leaves as hypoosmotic as salt is being reabsorbed
Salt is still being reabsorbed in the DCT and water isn’t due to absent AQP2.
Salt is still reabsorbed in collecting duct via sodium channels and NaKATPase Pump
Towards inner side of collecting duct water can be reabsorbed through paracellular pathways
Results in hypoosmotic urine
What happens during atudiuresis?
High number of ADH
Salt and water reabsorbed in the DCT since there are AQP2 and same in collecting duct
Therefore concentrated urine
What does ADH support Na+ reabsorption in?
Thick ascending limb via NaK 2Cl Symporter
DCT via NaCl symporter
Collecting duct via Na+ channel
What causes Central Diabetes Insipidus?
What are the clinical features?
What is the treatment?
Decreased/negligent production of ADH - could be due to genetics or acquired (e.g. trauma/infection)
Polyuria, polydipsia
External ADH
What causes Syndrome of inappropriate ADH secretion?
What are the clinical features?
What is the treatment?
Increased production and release of ADH
Hyperosmolar urine
Hypervolemia
Hyponatremia
Non-peptide inhibitor of ADH receptor (conivaptan & tolvaptan)
What causes Nephrogenic Diabetes Insipidus?
What are the clinical features?
What is the treatment?
Less/mutant AQP2
Mutant receptor
Polyuria, polydipsia
Thiazide diuretics (slowing filtration at Bowmans Capsule) , NSAIDs
Where do acid and base get added from?
Diet and Metabolism
How do we lose base and what does it result in?
Through feces
Net addition of Metabolic Acid
How is metabolic acid neutralised?
Through different buffer systems such as bicarbonate
What is the role of the kidneys in acid base balance?
Secretion and excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
What does Henderson-Hasselbalch equation show?
How H+ and HCO3- affects pH
What causes a respiratory acid base disorder?
Change in pCo2
What cases a metabolic acid base disorder?
Change in HCO3-
Where is the majority of HCO3- reabsorbed?
In the PCT
How is bicarbonate ions reabsorbed in the PCT?
CO2 enters cells through diffusion
H+ and HCO3- produced
H+ enters tubular fluid via Na+H+ antiporter or via H+ATPase pump
HCO3- reabsorbed into blood via Na+HCO3- symporter
Where do you find a-intercalated cells and b -intercalated cells?
DCT and Collecting Duct
What does b-intercalated cells do?
How does this happen?
HCO3- reabsorption and H+ secretion
H+ATPase Pump and H+K+ATPase
Cl-HCO3- Antiporter- blood
What does b-intercalated cells do?
How does this happen?
HCO3- secretion and H+ reabsorption
Cl-HCO3- Antiporter
H+ATPase Pump-blood
How are new bicarbonate ions produced in the PCT?
Glutamine is converted to 2 NH4+ and A2-
A2- turns into 2 HCO3- and reabsorbed
2 NH4+ goes into tubular fluid by Na+H+ antiporter (replaces H+) or becomes NH3 and then binds with H+ to become NH4+
How are new bicarbonate ions produced in the DCT and collecting duct?
In the tubular fluid, the H+ is neutralised by the phosphate buffer system and a new bicarbonate ion is gained
What are the characteristics of metabolic acidosis?
What is the compensatory response?
What are the characteristics of metabolic acidosis?
What is the compensatory response?
What are the characteristics of metabolic alkalosis?
What is the compensatory response?
What are the characteristics of respiratory acidosis?
What is the compensatory response?
What are the characteristics of respiratory alkalosis?
What is the compensatory response?
