Renal Regulation of Water and Acid-Base Balance Flashcards
What is osmotic pressure?
What is it proportional to?
The side pulling the particles
It is proportional to the no. of solute particles
What is osmolarity and it’s formula?
Osmolarity = Concentration x No. of dissociated particles
= Osm/L OR mOsm/L (units for osmolarity)
Is osmolarity always the same as osmotic pressure?
No, because osmolarity is also dependent on number of dissociated particles
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 body fluid volume?
Where are they found int he body?
60% of body weight
2/3 of fluid sits intracellularly
1/3 of fluid sits in the extracellular fluid (ECF)
Of the ECF, 1/4 is plasma (intravascular) and 3/4 is extravascular
Of the extravascular fluid, 95% is interstitial fluid and 5% is transcellular fluid
Give examples of trans-cellular fluid?
CSF
Periotoneal fluid
What are the unregulated forms of water loss?
What is regulated water loss?
Unregulated = sweat, faeces, vomit, water evaporation from respiratory lining and skin
Regulated = renal regulation - urine production
In the body, what is positive water balance VS negative water balance?
Positive = having drunk lots of water (so lots of water within the body)
Negative = thirsty (need to drink more water)
How do your kidneys normalise a positive water balance VS a negative water balance?
Positive water balance = High water intake enters EC compartment ECF volume increases Sodium conc decreases Osmolarity decreases Hypo-osmotic urine production Osmolarity normalises
Negative water balance = Low water intake Low ECF volume High sodium conc Osmolarity increases Hyper-osmotic urine production Osmolarity normalises
How does water reabsorption occur in the nephrons?
In the PCT = 67% (2/3) water reabsorbed (as 67% of salt is reabsorbed)
Water is not re-absorbed in the ascending limb of the loop of Henle (but salt is)
Water is re-absorbed in descending limb of the loop of Henle (but no salt is)
DCT and CD = variable amount of water is reabsorbed depending on vasopressin / ADH
Why is the loop of Henle designed the way it is?
To make water reabsorption passive
As active reabsorption of water = energy wasting
Actively pumping out salt to change water osmolalities = passive reabsorption of water
The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and CD
What is the countercurrent multiplication system of the loop of Henle?
What is the osmolarity of the interstitial fluid at the top of the loop of Henle VS the bottom?
Filtrate arrives at loop of henle at osmolarity equal to plasma
Salt reabsorbed by being actively pumped out of ascending loop of henle into interstitual fluid
Osmolarity of interstitial fluid = increased
Osmotic pressure gradient from loop of Henle to interstitial fluid established
Water passively flows into interstitial from thin descending
Fresh filtrate arrives - process repeats itself
300 mOsm/L at top
1200 mOsm/L at bottom
How does urea contribute to water reabsorption?
What is this process called?
In the CD, the apical membrane faces the CD and the basolateral membrane faces the interstitial fluid
Filtrate arrives at collecting duct where there are two urea transporters, one on basolateral and one on apical membrane
The 2 urea transporters = UTA-1 and UTA-3
As urea is pumped out, it reaches the medullary interstitum and increases its osmolarity
Can be reabsorbed in the vasa recta (via UT-B1) and the thin descending limb of the loop of Henle via (UT-A2)
Urea keeps being recycled
Urea helps reabsorption of water in the descending limb and CD
This process is called urea recycling
Why recycle urea?
Increasing interstitium osmolarity = helps water reabsorption
Recycling the urea = urine concentration occurs in the CD so urea excretion requires less water
How does vasopressin affect urea?
Increases permeability of CD to urea by boosting UT-A1 and UT-A3
Leads to greater water reabsorption
Where does IV fluid infusion travel to first?
First enters ECF - whether orally or IV
After some time, it equilibrates with the ICF compartment
What is vasopressin / ADH (anti-dieuretic hormone)?
Where is it produced, stored and released?
9 amino acids long
Promotes water reaborption from CD
Produced in hypothalamus in the supraoptic neurons and paraventricular nuclei)
Stored in the posterior pituitary
What affects ADH production and release?
What detects plasma osmomlarity
Stimulates ADH production and release =
Increased plasma osmolarity
Hypovolemia
Decreased BP
Inhibits ADH production and release =
Decreased plasma osmolarity
Hypervolemia
Increased BP
Plasma osmolarity is detected by osmoreceptors
What inhibits ADH production?
Alcohol e.g. ethanol reduces ADH production = increased water loss = feeling dehydrated
ANP
What is the mechanism of ADH?
ADH arrives via blood vessel to V2 receptor on the epithelial cells of the CD
Binds to V2 receptor = G-protein mediated signalling cascade activates cAMP, cAMP activates protein kinase A
Increase in PKA stimulates an intracellular cascade which promotes secretion, movement + insertion of aquaporin 2 into the apical membrane of collecting duct (on tubular side) so water moves in from the urine (in lumen) to inside the cell
Water flows along concentration gradient out of the cell and into the plasma through aquaporin-3/ 4 channels on basolateral side
This process promotes reabsorption of water from collecting duct = lower volume more conc urine
ADH can up/downgrade number of AQP2 (on apical membrane) & AQP3 (on basolateral membrane) as required
What happens in the nephrons when ADH is very low?
PCT = 67% water and 67% salt reabsorbed
In DCT = hypoosmotic
Small amount of ADH = absence of aquaporin-2 (AQP2) channels on the CD = less water reabsorbed in the CD
Urine more dilute
How is NaCl reaborbed in the thin ascending limb?
Top of ascending limb: Na+ and Cl- actively pumped out of tubular fluid into medulla, but this bit is impermeable to water, water stays inside tubule. Creates low water potential in medulla/ high osmolarity
Na+/K+/ATPase on basolateral: pumps Na+ into interstitial fluid to be reabsorbed Na+/K+/ 2Cl- symporter on apical side: Na+, Cl-, K+ enter using Na+ gradient K+/Cl- symporter on basolateral: takes Cl- into interstitial fluid using K+ gradient
Low Na+ and Cl- inside cell:
Net movement of Na+ and Cl- out of tubular fluid so hypoosmotic fluid leaves loop of Henle
