Renal Regulation of Water and Acid-Base Balance Flashcards
What is the relationship between osmotic pressure and the number of solute particles?
proportional
What is osmolarity?
Measure of solute in a concentration of a solution
Does not equal concentration
How do you calculate osmolarity?
concentration x number of dissociated particles (Osm/L, mOsm/L)
What is the difference between plasma and urine osmolarity?
Plasma osmolarity is constant and urine osmolarity is variable
Where is the majority of body fluid found?
2/3 in the intracellular fluid
Where is the 1/3 of extracellular fluid found?
- 80% interstitial fluid (extravascular)
- 20% plasma
What are the different forms of unregulated water loss?
- sweat
- feces
- vomit
- water evaporation from respiratory lining and skin
What is the form of regulated water loss?
renal regulation (urine production)
What are the 2 different forms of renal regulation?
positive and negative water balance
What is positive water balance?
- high water intake
- increased ECF volume
- reduced Na+ concentration
- reduced osmolarity
- hypoosmotic urine production
- osmolarity normalises
What is the first compartment of the body where new fluid is put?
ECF
What is negative water balance?
- low water intake
- reduced ECF volume
- increased [Na+]
- increased osmolarity
- hyperosmotic urine production
- thirst induced
- osmolarity normalizes
Where is the majority (67%) of water reabsorbed?
the distal convoluted tubule
What is absorbed in the ascending limb of the loop of Henle?
- Thin: passive NaCl
- Thick: active NaCl
no water
What is the only place in the kidney nephron where water is passively reabsorbed?
Descending loop of Henle
What is absorbed in the descending limb of the loop of Henle?
- water (passive)
- no NaCl
How are electrolytes transported into the blood in the thick ascending loop of henle?
- Na+/K+/2Cl- triple sympoter passively reabsorbs all three from the filtrate at the apical side of the membrane
- sodium transported into blood and potassium into cell through Na+/K+ ATPase pump via active transport
- K+/Cl- symporter pumps the ions into blood passively
Where is the concentration of sodium and chloride ions higher in the nephron?
Medullary interstitium
What is required for water to be reabsorbed at the descending loop of Henle by osmosis?
the medullary interstitium needs to be hyperosmotic to create a gradient since osmosis is passive
What process creates the gradient between the medullary interstitium and loop of Henle?
- countercurrent multiplication
- makes medulla hyperosmolar
How does countercurrent multiplication work?
- osmolarity is equal in ALH, DLH and interstitium (isosmotic)
- ions actively transported out of ALH into interstitium
- osmolarity is increased in interstitium and decreased in ALH
- water leaves DLH and osmolarity equilibrates with interstitium
- new fluid enters the LoH decreasing the osmolarity of the DLH
- new fluid reaches thin ALH, making it hyperosmolar
- ions are reabsorbed into the intersitium from the ALH but more from the thin part at bottom than thick part
- process continues, multiplying each time
- creates concentration gradient where osmolarity is highest at the bottom of the LoH and interstitium and lowest at the top
What does the A/B in UT-A/B stand for?
Apical or basolateral
Where do basolateral transporters transport ions to?
Blood
Which proteins transport urea from the collecting duct to the medullary interstitium?
UT-A1, UT-A3
What are the 2 possible locations for urea to go to once in the medullary interstitium?
- the descending loop of Henle
- the Vasa-Recta
Which protein transports urea into the Vasa Recta?
UT-B1
What transporters allows for the movement of urea into descending LoH?
UT-A2
What is the purpose fo urea recycling?
to increase the interstitial osmolarity
- causes urine concentration independent of water
- urea excretion needs less water (high concentrations can be excreted)
How is ADH/vasopressin involved in urea recycling?
boosts UT-A1 and UT-A3 numbers
What is the main function of ADH/vasopressin?
- promote water reabsorption from the collecting duct
- urea and sodium reabsoprtion
Where is ADH produced?
- hypothalamus
- neurons in the supraoptic and paraventricular nuclei
Where is ADH stored?
the posterior pituitary gland
What detects fluctuation in plasma osmolarity?
osmoreceptors in the hypothalamus
What factors stimulate ADH production and release?
- increased plasma osmolarity
- hypovolemia (reduced BP)
- nausea
- angiotensin II
- nicotine
What factors inhibit ADH production and release?
- low plasma osmolarity
- hypervolemia (increased BP)
- ethanol
- ANP,BNP
What detects changes in BP?
baroreceptors to the hypothalamus
What is required in order for baroreceptors to detect BP changes?
5-10% change in blood pressure
What receptor binds ADH?
V2 receptor
What happens when ADH binds to a V2 receptor?
- activates the G protein mediated signalling cascade
- adenylate cyclase converts ATP to cAMP
- activates protein kinase A
- increase the secretion of Aquaporin 2 channels that are transporters of water on apical membrane of collecting duct cells
How is water reabsorbed into the blood?
aquaporin 3 and 4 on basolateral membrane
What is diuresis?
increased dilute urine secretion (low/no ADH)
What is absorbed in the collecting duct during diuresis?
- water is passively reabsorbed into outer medulla
- NaCl actively reabsorbed in outer medulla and passively reabsorbed in inner medulla
What is the type of fluid that enters the LoH?
Isosmotic
What is the type of fluid that enters the DCT?
Hypoosmotic
What is reabsorbed in the DCT during diuresis?
- NaCl actively rabsorbed
- no aquaporins so no water reabsorption
What is the type of fluid that exits the CD?
hypoosmotic
How is sodium reabsorbed in the collecting duct?
- Na+/K+/ATPase Pump
- sodium channels
What is antidiuresis?
- concentrated urine in low volume excretion
- high ADH
How does ADH increase salt reabsorption in the thick ascending limb?
increased number/action of the Na+/K+/2Cl- symporter
How does ADH increase salt reabsorption in the DCT?
increased number/action of the Na+/Cl- symporter
How does ADH increase salt reabsorption in the CD?
increased Na+ channels
What is reabsorbed in the DCT during antidiuresis?
- NaCl via active transport
- water through AQP2
What is reabsorbed in the CD during antidiuresis?
- water reabsorbed increases as passing into the medulla
What are some examples of ADH related clinical disorders?
- vasopressin deficiency
- syndrome of inapropriate ADH secretion (SIADH)
- vasopression resistance
What is the cause of vasopressin deficiency?
decreased/negligent production/release of ADH
What are the clinical features of vasopressin deficiency?
- polyuria
- polydipsia
What is the treatment given for vasopressin deficiency?
external ADH
What is the cause of SIADH?
increased production and release of ADH
What are the clinical features of SIADH?
- hyperosmolar urine
- hypervolemia
- hyponatremia
What is the treatment given for SIADH?
Non-peptide inhibitor of ADH receptor (conivaptan and tolvaptan)
What is the cause of vasopressin resistance?
- less/mutant AQP2
- mutant V2 receptors
What are the clinical features of vasopressin resistance?
- polyuria
- polydipsia
What is the treatment of vasopressin resistance?
Thiazide diuretics and NSAIDs
How are acids and bases removed from the body?
- bases lost in faeces
- acids not excreted, must be neutralised to maintain pH
What mechanisms neutralise excess metabolic acids?
Bicarbonate buffering mechanism
What is the metabolic role of kidneys?
- secretion and excretion of H+
- reabsorption of HCO3-
- production of new HCO3-
What is the Hendersson-Hasselbach equation
How much of bicarbonate ions are reabsorbed in the PCT?
80%
How much of bicarbonate ions are reabsorbed in the ascending LoH?
10%
How much of bicarbonate ions are reabsorbed in the CD?
4%
How is bicarbonate reabsorbed into blood from the tubular fluid in the PCT?
- NHE3: Na+/H+ antiporter on the apical membrane
- H+ATPase on the apical membrane
- NBC1: Na+/HCO3- symporter on the basolateral membrane
- Na+/K+ ATPase pump on the basolateral membrane
Where are intercalated cells found?
Distal convoluted tubule and collecting duct
What is the role of the alpha-intercalated cells?
- HCO3- reabsorption
- H+ secretion
(alpha for acid secretion)
What is the role of the beta-intercalated cells?
- HCO3- secretion
- H+ reabsorption
(b for base secretion)
What happens in the alpha-intercalated cell?
- H+ back into tubular fluid via H+ATPase and H+/K+ ATPase
- HCO3- into blood by Cl-/HCO3- antiporter
What happens in the beta-intercalated cell?
- HCO3- into tubular fluid by Cl-/HCO3- antiporter
- H+ ATPase pump for H+ into the blood
Where are new bicarbonate ions produced
PCT
How is new bicarbonate produced?
- glutamine broken into 2 ammonia and 2 HCO3-
What happens if ammonia reaches the blood and eventually back to the liver?
- breaks down into urea and H+
- then uses up another HCO3- for neutralisation
How do you prevent ammonia from reentering the blood stream and reaching the liver?
- secreted via NHE3 antiporter with H+
- diffuses out as NH3 gas
- H+ in tubular fluid binds to NH3 to produce NH4
How is bicarbonate produced in the DCT and CD?
- by alpha intercalated cells
- carbonic anhydrase catalyses conversion of water and carbon dioxide into hydrogen ions and bicarbonate
- bicarbonate absorbed into blood via Cl-/HCO3- antiporter
What happens to the excess proton when HCO3- is produced in the DCT and CD?
it is neutralised by phosphate in the tubule
What are the characteristics of metabolic acidosis?
- low [HCO3-]
- low pH
What are the characteristics of metabolic alkalosis?
- high [HCO3-]
- high pH
What is the compensatory response to metabolic acidosis?
- acute = increased ventilation
- chronic = increased [HCO3-] reabsorption and production
What is the compensatory response to metabolic alkalosis?
- acute = hypoventilation
- chronic = increased [HCO3-] excretion
What are the characteristics of respiratory acidosis?
- high pCo2
- low pH
What is the compensatory response to respiratory acidosis?
- acute = intracellular buffering
- chronic = increase [HCO3-] reabsorption and production
What are the characteristics of respiratory alkalosis?
- low Pco2
- high pH
What is the compensatory response to respiratory alkalosis?
- acute = intracellular buffering
- chronic = increase [HCO3-] excretion and reduced [HCO3-] production
What sort of gradient does countercurrent multiplication create?
creates concentration gradient where osmolarity is highest at the bottom of the LoH and interstitium and lowest at the top of the LoH
