Renal regulation of water and acid-base balance Flashcards
What is osmotic pressure proportional to?
Number of solute particles
What is osmolarity equal to?
Concentration x No. of dissociated particles
What are the units of osmolarity?
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
What is the total fluid volume of the body?
60% of body weight
What proportion is extracellular and intracellular?
1/3 extracellular
2/3 intracellular
Give examples of trans-cellular fluid?
CSF
Periotoneal fluid
What comprises extracelllular fluid?
Transcellular
Interstitial
Plasma
What are the unregulated forms of water loss?
Sweat
Feces
Vomit
Water evaporation from respiratory lining and skin
What is the regulated form of water loss?
Renal regulation – urine production
What happens when there is a positive water balance?
High water intake enters EC compartment
ECF volume increases
Sodium conc decreases
Osmolarity decreases
Hypo-osmotic urine production
Osmolarity normalises
What happens when there is a negative water balance? (low water intake)
Low water intake
Low ECF volume
High sodium conc
Osmolarity increases
Hyper-osmotic urine production
Osmolarity normalises
What percentage of water is absorbed in the PCT?
67%
What occurs in the descending limb of the loop of henlé?
Water is passively absorbed
Salt is not reabsorbed
Why is an osmotic gradient in the loop of henle essential?
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.
What is countercurrent multiplication?
Filtrate arrives at loop of henle at osmolarity equal to plasma
Salt is actively reabsorbed into interstitial from ascending
Water passively flows into interstitial from thin descending
Fresh filtrate arrives
Active salt reabsorbed into interstitium again from ascending
Water from descending equilibrates by passively moving into interstitium
What is the gradient that can be achieved via countercurrent mulitplcation?
300 at top
1200 at bottome
What is urea recycling?
Urea contributes to the concentrating of the interstitium
Filtrate arrives at collecting duct where there are two urea transporters on basolateral (UT-A3) and on apical membrane (UT-A1)
Urea pumped out to medullary interstitum, increases osmolarity
Can be reabsorbed by vasa recta by UTB-1 transporter
But also reabsorbed to filtrate by descending limb of loop (UT-A2) aka urea recycling
What are the two goals of urea recycling?
Urea excretion requires less water due to high osmolarity at bottom
Increases interstitium osmolarity to aid water reabsorption process
Where does IV fluid infusion first enter?
Extracellular compartment
What is the main function of ADH?
Promote water reabsorption from collecting duct
Where is ADH produced?
Hypothalamus (neurons in supraoptic & paraventricular nuclei)
Where is ADH stored?
Posterior pituitary
What happens when you are dehydrated?
Rise in plasma osmolarity is detected by osmoreceptors
Stimulates ADH production and release
What happens to inhibit ADH?
Decreased osmolarity
Hypervolemia
Increase in blood pressure
What other substances inhbit ADH?
Ethanol
ANP
How does ADH support water reabsorption?
ADH binds to V2 receptor
G-protein mediated signalling cascade activates cAMP
cAMP activates protein kinase A
What does ADH do with regards to aquaporins?
ADH up/downgrades AQP2 & AQP3 numbers as required
AQP2 on apical cell membrane (lumen side) AQP3 on basolateral (to blood)
also effects on UT-A3 and UT-A1 - icnreased permeability to urea - more reabsorption (less excretion)
How is sodium actively reabsorbed in PCT
NaK2CL triple transporter from lumen to tubular cell
Na+/K+ ATPase pump from tubular cell to blood
K+CL- symporter into blood
What is the conc of the fulid in DCT?
Hyposomotic
Why is some water reabsorbed in diuresis?
Paracelluar pathways
Some aquaporins function
How does ADH support Na+ reabsorption in the kidney?
Thick ascending limb: ↑Na+ - K+ - 2Cl- symporter
Distal convoluted tubule: ↑Na+ - Cl- symporter
Collecting duct: ↑Na+ channel
What are some ADH-related clinical disorders?
Central diabetes insipidus
Syndrome of inappropriate ADH secretion
Nephrogenic diabetes insipidus
What is the primary excretion of base?
Faeces
What does the excretion of bicarbonate lead to?
Net addition of Metabolic Acid
How are metabolic acids neutralised?
𝐻2𝑆𝑂𝟒+2𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎2𝑆𝑂4+2𝐶𝑂2+2𝐻2𝑂
𝐻𝐶𝑙+𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎𝐶𝑙+𝐶𝑂2+𝐻2𝑂
What is the ECF conc of bicarbonate?
ECF [HCO3-] = ~350mEq
What is the role of the kidneys to maintain acid-base balance?
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
How does bicarbonate act as a buffer?
𝑪𝑶𝟐+𝑯𝟐𝑶↔𝑯𝟐𝑪𝑶𝟑↔𝑯++𝑯𝑪𝑶𝟑−
What is the Henderson-hasselbalch equation?
𝒑𝑯=𝒑𝑲^′+𝒍𝒐𝒈 (𝑯𝑪𝑶𝟑−)/𝜶𝑷𝑪𝑶𝟐
[𝑯+]= (𝟐𝟒 𝐱 𝑷𝑪𝑶𝟐)/([𝑯𝑪𝑶𝟑−])
What is a disorder caused by pCO2 called?
Respiratory
What is a disorder caused by bicarbonate called?
Metabolic
How is bicarbonate reabsorbed to the blood in the PCT?
H+ and HCO3- are converted to H2CO3 then H2O and CO2 by carbonic anhydrase
CO2 diffuses into the PCT cell
carbonic anhydrase converts this back to H+ and HCO3-
the Na+ HCO3- symporter drives this back into the blood through the basolateral membrane
H+ goes back into the tubular fluid by Na+/H+ antiporter and via H+ ATPase transporter (apical side)
How is bicarbonate reabsorbed in DCT and collecting duct?
H+ and HCO3- are converted to H2O and CO2 in the tubular fluid (carbonic anhydrase)
CO2 diffuses into DCT/collecting duct, converted back by carbonic anhydrase
HCO3- pumped to blood by Cl- HCO3- antiporter
H+ secreted by H+ ATPase pump and H+ K+ATPase
all within alpha intercalated cells
How are new bicarbonate ions produced?
PCT - ammoniogenesis
DCT and collecting duct - carbonic anhydrase
Describe the process of ammioniogenesis?
In PCT : glutamine broken down to NH4+ and A2- (A2 gives rise to two HCO3- which is reabsorbed)
NH4+ needs to be excreted so that the bicarb created is not wasted
Either becomes NH3 gas and diffuses out or forced out by Na+ NH4+ antiporter
What the characteristics of metabolic acidosis?
Reduced bicarbonate
Reduced pH
What the characteristics of metabolic alkalosis?
Increased bicarbonate
Increased pH
What is the compensatory mechanisms of metabolic acidosis?
Hyperventilation
Increased bicarbonate reabsorption and production
What is the compensatory mechanisms of metabolic alkalosis?
Decreased ventilation
Increased bicarbonate excretion
What the characteristics of respiratory acidosis?
Increased pCO2
Reduced pH
What the characteristics of respiratory alkalosis?
Decrease pCO2
Increased pH
What is the compensatory mechanisms of respiratory acidosis?
Acute intracellular buffering
Chronic Increased bicarbonate reabsorption and production
What is the compensatory mechanisms of respiratory alkalosis?
Acute Intracellular buffering
Chronic Decreased bicarbonate reabsorption and production
describe the process of forming new bicarbonate using carbonic anhydrase?
In DCT/collecting duct alpha intercalated cell: same process as in reabsorption but H+ in tubular fluid is bound to HPO42- to create H2PO4- which acts as a buffer and produces a net gain of HCO3 (reduced amount of H+)
describe the process of bicarbonate excretion in the DCT/collecting duct
H+ and HCO3- are converted to H2O and CO2 in the tubular fluid (carbonic anhydrase)
CO2 diffuses into DCT/collecting duct, converted back by carbonic anhydrase
HCO3- secreted into tubular fluid by CL- HCO3- antiporter
H+ reabsorbed to blood by H+ ATPase pump on basolateral membrane (b intercalated cells only)
how is sodium actively reabsorbed in DCT
NaCl symporter from lumen to tubular cell
NaKATPase pump to blood
K+Cl- symporter to blood
how is sodium actively reabsorbed in collecting duct
principal cells
passively enters cell
Na+K+ATPase pump into blood
