1b// Renal Regulation of Water and Acid-Base Balance Flashcards
How do you measure osmolarity and what are it’s units?
Concentration x number of dissociated particles
= Osm/ L or mOsm/ L
What is osmolality?
Osm/ Kg or mOsm/ kg
What is the osmolarity for 100mmol/ L of glucose and 100mmol/ L of NaCl?
glucose = 100mOsm/L
NaCl= 200mOsm/ L
What is osmotic pressure directly proportional to?
number of solute particles
What is a human’s body fluid distribution?
2/3 intracellular fluid
1/3 extracellular fluid
- of this 1/4 intravascular (plasma) and 3/4 extravascular
of the extravascular…
- 95% interstitial fluid
- 5% transcellular fluid
What separates intra and extracellular fluid?
cell membrane (phospholipid bilayer)
What separates extra and intravascular fluid?
capillary wall
Our total fluid volume is roughly how much of our body weight?
60%
What are examples of unregulated water loss? (4)
Sweat
Feces
Vomit
Water evaporation from respiratory lining and skin
What are regulated ways of water loss?
renal regulation (urine production- kidneys)
If you drink a lot of water does your urine become hyper or hypoosmotic?
Hypoosmotic
What happens to ECF, Na concentration and osmolarity when you drink lots of water?
increase ECF
decrease Na
Decrease in osmolarity
When you drink lots of water, do you require positive or negative water balance from renal regulation?
positive water balance
Describe positive and negative water balance.
*osmolarity normalises in the blood
*hyperosmotic urine is low in volume and dark in colour
How is water reabsorbed and what does it require?
passive process of osmosis and requries a gradient
Where is water reabsorbed in a nephron?
PCT
Descending limb of loop of Henle
Distal convoluted tubule
Collecting Duct
What does the loop of Henle and collecting duct require for water reabsorption?
The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and Collecting duct.
Where is most of the nephron and why?
in the cortex because there is more space
What 2 things happen in the loop of Henle?
Active salt reabsorption
Passive water reabsorption
How does active salt reabsorption and passive water reabsorption occur at the loop of Henle?
countercurrent multiplication (a continuous and dynamic process)
What is countercurrent Multiplication?
https://www.osmosis.org/learn/Kidney_countercurrent_multiplication
How does ICL describe countercurrent multiplication?
Water can be reabsorbed due to increased solute concentration within the juxtamedullary fluid. The ascending limb is effectively impermeable to water.
Tight junctions present in the ascending limb decrease paracellular transport of water.
Sodium chloride passively diffuses upon the hairpin bend, within the thin ascending limb.
Sodium chloride is actively transported out of the thick ascending limb.
N.B: Upon entering the descending limb of the loop of Henle, the filtrate is isotonic with the plasma.
Active salt reabsorption into the juxtamedullary interstitium by the thick ascending limb, reducing the water potential such that a gradient is established.
Passive water reabsorption through osmosis from the thin descending limb into
the hyperosmolar interstitium.
What would the 2 steps of countercurrent multiplication look like?
What is urea recycling according to osmosis?
Ut-A1
https://www.osmosis.org/learn/Urea_recycling
What is urea recycling according to ICL?
1) Urea enters the thin descending limb via UT-A2
2) At the collecting duct urea leaves via UT-A1 (apical cell membrane) then into interstitium via UT-A3 (basolateral cell membrane)
3) this increases interstitium osmolarity
4) Urine concentration occurs
5) then a small amount of urea from the interstitium enters the vasa recta via UT-B1
What increases UT-A1/3 numbers?
Vasopressin
- urea excretion requires less water
True or False.
NaCl and Urea are both responsible for generating hyperosmotic medullary interstitium.
True
True or False.
Intravenous fluid infusion first enters the intracellular fluid (ICF) and then travels to the ECF compartment.
False
True or False.
Osmolarity for 100mmol/ L NaCl is less than 200mmol/ L of Na+ ions.
False
What is ADH (like biomolecule) and how big is it?
protein
9 AA long
What is the main function of ADH?
Promote water reabsorption from collecting duct
Where is ADH stored?
Posterior Pituitary
Where is ADH produced?
Hypothalamus (neurons in supraoptic & paraventricular nuclei)
What stimulate ADH production? (5)
increased plasma osmolarity
decreased blood pressure
angiotensin II
Nicotine (antidiuretic)
Hypovolaemia
What inhibits ADH production and release? (5)
decreased plasma osmolarity
hypervolaemia
increased bp
ethanol
atrial natriuretic peptide
How much change isrequired to be detected (and how) to be transmitted to hypothalamus?
5-10% change required for detection by baroreceptors; information transmitted to hypothalamus.
What detects changes in plasma osmolarity? And what is a healthy adult’s osmolarity?
plasma osmolality: 275-290 mOsm/kg H20 (Healthy adult) Fluctuation detected by osmoreceptors in hypothalamus
What is the mechanism of action of ADH?
1) ADH binds to V2 receptors (basolateral side) on principal cells in the collecting duct
2) activates G protein on V2 receptor which activates adenylyl cyclase to turn ATP into cAMP
3) cAMP activates protein kinase A
4) protein kinase A triggering the translocation of aquaporins 2 from vesicles to the apical cell membrane
5) this causes more water to be reabsorbed into the cell via AQP2
6) water then leaves the cell on the basolateral side via AQP4 (and AQ3)
What does ADH upgrade?
AQP2 and 3
What is diuresis?
increased dilute urine excretion
Is there high or low ADH during diuresis?
low/ none
What happens at the thick ascending limb?
*Active Na Cl reabsorption
basolateral side:
1) NaK ATPase pump
- 2 K into cell
- 3 Na out of cell
2) KCl symporter
- 1 k and 1 Cl out of cell
3) facilitated diffusion of Cl via ion channels
apical side:
1) Na K 2Cl symporter
- 1 Na, 1 K, 2 Cl enter cell
2) facilitated diffusion of K out of cells via ion channels
What happens at the distal convoluted tubule?
*NaCl reabsorption
basolateral side:
1) Na K ATPase pump
- 2 K into cell
- 3 Na out of cell
2) K Cl symporter
- 1 k and 1Cl out of cell
3) facilitated diffusion of Cl via ion channels
apical side:
1) Na Cl symporter
What happens at the collecting duct?
*Principal Cell: Na+ reabsorption
basolateral side:
1) Na K ATPase pump
- 2 K into cell
- 3 Na out of cell
apical side:
1) facilitated diffusion of Na via ion channels into cell
What is the difference between diuresis and antidiuresis?
ADH amount is low during diuresis
- high during anti-diuresis
no aquaporins in distal convoluted tubule and collecting duct during diuresis
during anti-diuresis urine is roughly 1200 mOsm/ L (for diuresis it is roughly 50)
What are the 3 ADH related clinical disorders? (and their old names)
AVP deficiency
- central diabetes insipidus
Syndrome of inappropriate ADH secretion (SIADH)
AVP resistance
- nephrogenic diabetes insipidus
What is the cause, clinical features and treatment of AVP deficiency?
What is the cause, clinical features and treatment of SIADH?
What is the cause, clinical features and treatment of AVP resistance?
True or False.
One of the body’s response to increased plasma osmolarity is the trigger of thirst.
true
True or False.
ADH regulates the number of aquaporin channels on both the apical and basolateral membranes of the principal cells.
True
True or False.
The blood of patient suffering for SIADH will slowly get more hyperosmotic.
False
What are the equations for metabolic acid neutralisation?
What are the roles of the kidneys?
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
Where does metabolic water go from these equations?
goes to the kidneys
What is the ECF concentration of HCO3-?
roughly 350mEq or 24mEq/L
What is the arrow equation for diet metabolism?
What is the role of bicarbonate ion?
acts as a buffer
What is the ionic equation including bicarbonate ion and CO2?
What equation is used for measure pH?
If PCO2 caused an acid-base disorder, what type of disorder is it?
respiratory
If concentration of bicarbonate ion caused an acid-base disorder. what type of disorder is it?
metabolic
In the nephron how much bicarbonate ion is reabsorbed and where?
What main 2 places does bicarbonate ion reabsorption occur (that you need to know)?
PCT
DCT and collecting duct (alpha and beta cells)
What happens at the PCT?
basolateral side:
1) NaK ATPase pump on
2) Na HCO3 symporter side making them leave the cell
- called NBC1
- 1 Na and 3 HCO3
middle of the cell:
1) CO2 enters the cell via diffusion (lowkey basolateral side)
2) H + HCO –><– H20 + CO2
- via carbonic anhydrase
apical side:
1) Na H antiporter
- 1 H out of cell
- 1 Na into cell
- called NHE3
2) H ATPase pump
- called V-ATPase
- 1 H out of cell
outside of cell in tubular fluid:
1) H + HCO3 –> H2CO3 –> (CA) H2O + CO2
What happens at alpha intercalated cells of DCT and CD?
*HCO3- reabsorption and H+ secretion
basolateral side:
1) Cl HCO3 antiporter
- 1 Cl into cell
- 1 HCO3 out of cell
2) Cl facilitated diffusion via ion channel out of cell
inside cell;
1) H + HCO –><– H20 + CO2
- via carbonic anhydrase
apical side:
1) H ATPase pump
- called V-ATPase
- 1 H out of cell
2) H K ATPase
- 1 H out
- 1 K into cell
outside of cell:
1) H + HCO3 –> H2CO3 –> (CA) H2O + CO2
What happens at beta intercalated cells of the DCT and CD?
*HCO3- secretion and H reabsorption
basolateral side:
1) H ATPase pump
- called V-ATPase
2) facilitated diffusion of Cl via ion channel out of cell
inside cell:
1) H + HCO –><– H20 + CO2
- via carbonic anhydrase
apical side of cell:
1) Cl HCO3 antiporter
- 1 Cl into cell
- 1 HCO3 out of cell
What is the new bicarbonate ion production at the PCT?
Glutamine makes ammonium and A2-
The A2- makes bicarbonate which then enters the blood
ammonia leaves the cell via diffusion
ammonia also leaves via the NaH antiporter on the apical side
- NHE3
- 1 NH4 out and 1 Na in
antiporter NHE3 also makes H+ leave the cell
outside the cell…
H + NH3–> NH4
What is the new bicarbonate ion production at the DCT and CD?
outside of cell in tubular fluid
H + HPO4(2-) –> H2PO4-
What are the characteristics of metabolic acidosis and what is the compensatory response?
decreased HCO3- and decreased pH
increased ventilation and increased HCO3- reabsorption and production
What are the characteristics of metabolic alkalosis and what is the compensatory response?
increased HCO3- and increased pH
decreased ventilation and increased HCO3- excretion
What are the characteristics of respiratory acidosis and what is the compensatory response?
increased PCO2 and decreased pH
acute= intracellular buffering
chronic= increased HCO3- reabsorption and production
What are the characteristics of respiratory alkalosis and what is the compensatory response?
decreased PCO2 and increased pH
acute= intracellular buffering
chronic= decreased reabsorption and production of HCO3-
