Renal regulation of water and acid-base balance Flashcards
Describe the body’s fluid distribution in different compartments
- 2/3 Intracellular fluid
- 1/3 extracellular fluid (ECF)
Describe the different components of the extracellular fluid in order of abundance.
- Interstitial fluid (that surrounds and bathes cells) 70ish percent
What happens at the PCT in the kidney water wise?
2/3 of water gets reabsorbed
What happens at the descending loop of Henle water and ion wise?
- Water passively reabsorbed
- NaCl isn’t reabsorbed
What happens in the ascending loop of Henle?
- NaCl is reabsorbed passively in the thin ascending limb
- NaCl is also reabsorbed actively in the thick ascending limb
- Water can’t be reabsorbed
How does ADH work to regulate water reabsorption and where does it act?
ADH modulates aquaporin channels (open and closing them) to vary amount of water reabsorption, act on the DCT and collecting duct.
What happens at the DCT and collecting duct?
There’s a variable amount of water reabsorbed depending on body’s needs.
Action of ADH kicks in here.
How does the body passively reabsorb water into the body without spending a lot of energy. (2 words)
Countercurrent multiplication
In collecting duct cells what side does the basolateral cell membrane face?
The side with the blood capillaries
What side does the apical cell membrane face?
The lumen of the collecting duct (the inside of the tube)
What is the vasa recta?
A series of blood capillaries that surround nephron mainly in medullary region
How and where is urea transported out into the medullary interstitium?
Through UT-A1 and UT-A3 transporters in the inner collecting duct
Once the urea is in the interstitium what are its two paths?
-It can go into vasa recta through UT-B1 transporter which surrounds nephron
-It can go into descending limb of loop of Henle through UT-A2 transporter where it goes back through nephron and some exits collecting duct back into interstitium again
Which transporter is responsible for moving urea into the vasa recta?
UT-B1
Why is urea recycled?
To increase interstitium osmolarity which leads to helping conserve water.
When is vasopressin (ADH) released?
When plasma osmolality increases (dehydration)
What does vasopressin do to this mechanism?
Helps boost UT-A1 and UT-A3 numbers to increase collecting duct’s permeability for urea to aid urea reabsorption
What is Vasopressins main function?
Promote water reabsorption from collecting duct by increasing UREA and SODIUM reabsorbtion.
Where is ADH/ Vasopressin produced?
In hypothalamus by neurones in supraoptic and paraventricular nuclei
Where is ADH/Vasopressin then stored?
Once produced it’s packaged into granules and sent to posterior pituitary for storage
What does ADH do to the kidneys to conserve water?
leads to the insertion of aquaporin channels in collecting duct to reabsorb water.
What is hypovolemia?
Hypovolemia means low blood volume
Which receptors detect change in blood pressure?
baroreceptors
What other factors stimulate ADH production and release? (3)
- Nicotine
- Nausea
- Angiotensin II
What is the target of ADH in the collecting duct?
V2 receptor on basolateral membrane of principal cells of collecting duct.
What happens when ADH binds to V2 receptor?
It triggers a G-protein mediated signal cascade in the cell (protein kinase A involved) leads to the expression/ insertion of aquaporin channels.
What is the next step in the ADH signal pathway after the G-protein mediated signal cascade is triggered?
Protein kinase A gets activated.
What is the effect of protein kinase A activation in the ADH signal pathway?
It increases secretion of aquaporin 2 channels in vesicle form which are inserted into apical cell membrane.
How does water get absorbed into the blood vessel in the collecting duct?
Water is absorbed through aquaporin 2 into the cell, and then through aquaporin 3 and 4 in the basolateral cell membrane into the lumen.
What is diuresis?
Increased excretion of dilute urine
At a cellular level how is NaCl reabsorbed in thick ascending limb?
Through Na+ K+ 2Cl- symporter
At a cellular level how is NaCl reabsorbed in the DCT?
Through Na+ K+ ATPase pump, Na+ is pumped into blood
Where are principal cells found?
In the collecting duct.
What causes central diabetes insipidus?
Decreased/negligent production and release of ADH.
Clinical features of central diabetes insipidus?
- Polyuria- large urine volume
- Polydipsia- thirst
How do you treat central diabetes insipidus?
External ADH
What causes/ is Nephrogenic Diabetes Insipidus?
Correct amount of ADH produced but something going wrong at collecting duct?
- Fewer/mutant AQP2
- Mutant V2 receptors
How do you treat nephrogenic diabetes insipidus?
- Thiazide diuretics- reduce filtration rate at Bowman’s capsule so less blood filtered so less urine produced
- NSAIDs
What is Symptom of inappropriate ADH secretion (SIADH)?
Increased unnecessary production and release of ADH
Clinical features of Symptom of inappropriate ADH secretion (SIADH)?
- Hyperosmolar urine
- Hypervolemia
- Hyponatremia
How do you treat Symptom of inappropriate ADH secretion (SIADH)?
Giving two examples.
Non peptide inhibitor of ADH receptor (conivaptan and tolvaptan)
What do the kidneys do to help maintain blood ph?
- Reabsorption of 100% of HCO3-
- Production of new HCO3-
- Helps secrete and excrete H+ ions
What is the enzyme that converts CO2 and H2O into carbonic acid? (H2CO3)
Carbonic anhydrase
What is an acid-base disorder due to changes in PCO2 called?
Respiratory disorder
What is an acid-base disorder due to changes in HCO3- conc called?
Metabaolic disorder.
Where is most of the HCO3- reabsorbed in the nephron?
80% in the PCT
What does alpha intercalated cell do?
HCO3- reabsorption and H+ secretion
What does beta intercalated cell do?
HCO3- secretion and H+ reabsorption
Describe how new HCO3- is produced at PCT
1) glutamine molecules gives 2 NH4+ molecules and 1 divalent ion (A2-) which gives rise to 2 HCO3-
2) The 2 NH4+ is excreted into tubular fluid
- Through Na+ H+ antiporter (NH4+ substitutes in place of H+)
- Turns into NH3 and moves into tubular fluid where it combines with a H+ to form NH4+ again
How is metabolic acidosis characterised?
Decrease in HCO3- conc leading to decrease in pH
What is the compensatory response for metabolic acidosis
- Increased (hyper)ventilation which kicks in first → PCO2 goes down so H+ conc goes down
- Increased HCO3- conc reabsorption and production to compensate for decrease in conc
How is metabolic alkalosis characterised?
Increased HCO3- conc leading to increased pH
What is the compensatory response for metabolic alkalosis?
- Decreased (hypo)ventilation which kicks in first → PCO2 goes up so H+ conc goes up
- Increased HCO3- conc excretion to compensate for increase in conc
How is respiratory acidosis characterised?
Increased PCO2 leading to lower pH
How is respiratory alkalosis characterized?
Decreased PCO2 leading to higher pH
What is a normal HCO3- conc?
24mEq/L (REMEMBER THE NUMBER)
What is a normal blood pH?
7.4
