RENAL REGULATION OF WATER AND ACID BASE BALANCE

Question 1

How do you calculate osmolarity?

Answer 1

Concentration x no. of dissociated particles

100mmol/L NaCl = 200 mOsm/L

Question 2

How is body fluid distributed?

Answer 2

2/3 intracellular fluid

1/3 extracellular:

• 95% interstitial fluid
• 25% intravascular fluid
• 5% transcellular fluid

Question 3

Give examples of unregulated water loss

Answer 3

Sweat
Faeces
Vomit
Water evaporation from respiratory lining and skin

Question 4

In which parts of the nephron does water reabsorption occur?

Answer 4

DCT (67%)
Thin descending limb (15%)
Thin ascending limb
Collecting duct

Question 5

In which parts of the nephron does Na+ Cl- reabsorption occur?

Answer 5

Thin ascending limb (passive)

Thick ascending limb (active)

Question 6

What is countercurrent multiplication?

Answer 6

Allows the continued reabsorption of water and production of concentrated urine

Thick ascending limb actively pumps salt out into interstitial fluid which becomes hyperosmolar.
Passive water reabsorption from descending limb due to this concentration gradient so equilibrium is reached.

New tubular fluid enters descending limb and pushes the relatively hyperosmolar fluid down.

These 2 steps repeat and the osmotic gradient of the medullary interstitium forms

Question 7

How does urea recycling work and what does it result in?

Answer 7

Some urea in the collecting duct is reabsorbed into the interstitium by UT-A1 and UT-A3.

The urea then is either transported into the vasa recta by UT-B1 or re-enters the thin descending limb by UT-A2 to make its way back to the collecting duct.

Urine concentration occurs due to increased interstitium osmolarity.
Urea excretion requires less water since urea levels in collecting duct equilibrate with interstitium levels (600 mmol/L) so more urea excreted in same amount of water

Question 8

What is the vasa recta?

Answer 8

Blood capillaries surrounding nephron

Question 9

What are the effects of vasopressin/AVP/ADH on urea recycling?

Answer 9

Increases UT-A1/A3 levels so more urea is reabsorbed

Question 10

What factors stimulate ADH production and release?

Answer 10

Increased plasma osmolarity
Decreased BP
Hypovolemia
Nausea
Angiotensin II
Nicotine

Question 11

What factors inhibit ADH production and release?

Answer 11

Decreased plasma osmolarity
Increased BP
Hypervolemia
Ethanol
Atrial natriuretic peptide

Question 12

How is plasma osmolarity detected?

Answer 12

Osmoreceptors in hypothalamus

Question 13

How is blood pressure detected?

Answer 13

Baroreceptors

Question 14

How does ADH work?

Answer 14

Binds to G linked V2 receptor on basolateral membrane of collecting duct cell. Increases aquaporin-2 channels on apical membrane and aquaporin-3 channels on basolateral membrane allowing increased water reabsorption

Question 15

During diuresis how does the nephron increase dilute urine excretion?

Answer 15

NaCl reabsorption in thick ascending limb by apical Na+/K+/2Cl- symporter, basolateral Na+/K+ ATPase pump and K+/Cl- symporter

NaCl reabsorption in distal convoluted tubule by apical Na+/Cl- symporter, basolateral Na+/K+ ATPase pump and K+/Cl- symporter

Na+ reabsorption in collecting duct principal cells by apical Na+ ion channel and basolateral Na+/K+ ATPase pump.

Some water is still reabsorbed in the collecting duct even with 0 ADH due to paracellular pathways

Question 16

During antidiuresis how does the nephron increase concentrated urine in low volume excretion?

Answer 16

High ADH supports Na+ reabsorption:

• Increased Na+/K+/2Cl- symporter (thick ascending)
• Increased Na+/Cl- symporter (DCT)
• Increased Na+ channel (collecting duct)

This increases interstitium osmolarity so more water can be reabsorbed

Aquaporin channels in DCT and collecting duct
As you go down collecting duct more and more water is reabsorbed due to interstitial gradient

Question 17

Name 3 ADH related disorders

Answer 17

Central diabetes insipidus
Syndrome of inappropriate ADH secretion (SIADH)
Nephrogenic diabetes insipidus

Question 18

What is the cause, clinical features and treatment of central diabetes insipidus?

Answer 18

Cause: Decreased/negligent production and release of ADH (genetic)

Clinical features: Polyuria, polydipsia

Treatment: External ADH

Question 19

What is the cause, clinical features and treatment of SIADH?

Answer 19

Cause: Increased production/release of ADH

Clinical features: Hyperosmolar urine, hypervolemia, hyponatremia

Treatment: Non-peptide inhibitor of ADH receptor (conivaptan, tolvaptan)

Question 20

What is the cause, clinical features and treatment of nephrogenic diabetes insipidus?

Answer 20

Cause: Less/mutant AQP2, mutant V2 receptor

Clinical features: Polyuria, polydipsia

Treatment: Thiazide diuretics (paradoxical - reduces eGFR), NSAIDs

Question 21

What causes the need for acid-base balance?

Answer 21

Acid and base derived from diet and metabolism

Base excretion in faeces so need to neutralise net addition of metabolic acid

Question 22

Which organ carries out acid-base balance and how do they do it?

Answer 22

Kidneys

• Secretion and excretion of H+
• Reabsorption of HCO3- (almost 100%)
• Production of new HCO3-

Question 23

What should the ECF concentration of HCO3- be?

Answer 23

24 mEq/L

Question 24

Where are bicarbonate ions reabsorbed in the nephron?

Answer 24

PCT (80%)
Thick ascending limb (10%)
DCT (6%)
Collecting duct (4%)

Question 25

What is the relationship between [H+] and [HCO3-]

Answer 25

[H+] is inversely proportional to [HCO3-]

Question 26

How is HCO3- reabsorbed in the PCT?

Answer 26

CO2 enters cell from tubular fluid via diffusion. Reacts with water catalysed by carbonic anhydrase H+ formed is secreted by: - Na+/H+ antiporter - H+ ATPase pump HCO3- formed is reabsorbed by: - Na+/HCO3- symporter

Question 27

How do alpha intercalated cells of DCT and collecting duct contribute to acid base balance?

Answer 27

HCO3- reabsorption and H+ secretion H+ formed is secreted by: - H+ ATPase pump - H+/K+ ATPase HCO3- formed is reabsorbed by: - Cl-/HCO3- antiporter

Question 28

How do beta intercalated cells of DCT and collecting duct contribute to acid base balance?

Answer 28

HCO3- secretion and H+ reabsorption HCO3- secreted by: - Cl-/HCO3- antiporter H+ reabsorbed by: - H+ ATPase pump

Question 29

Where does new bicarbonate ion production occur?

Answer 29

``` PCT DCT (alpha intercalated cell) Collecting duct (alpha intercalated cell) ```

Question 30

How do cells in the PCT produce new bicarbonate ions?

Answer 30

Glutamate into 2NH4+ and a divalent ion Divalent ion into 2HCO3- and reabsorbed into blood NH4+ secreted by: - Na+/H+ antiporter (ammonia replaces H+) - Into NH3 which diffuses through NH3 then react with H+ in tubular fluid and excreted with rest of NH4+ Ammonia cannot enter blood because if it does it goes to liver where its converted to a urea ion and H+. The H+ will require a HCO3- for neutralisation so no net gain of HCO3-

Question 31

How do the alpha intercalated cells of the DCT and collecting duct produce new bicarbonate ions?

Answer 31

H20+CO2 --> H+ + HCO3- in cell HCO3- into blood by apical Cl-/HCO3- antiporter. H+ into tubular fluid by: - H+ ATPase pump - H+ K+ ATPase In tubular fluid HPO4 2- acts as a non-bicarbonate buffer reacting with the H+ forming H2PO4- and excreted

Question 32

What are the characteristics of metabolic acidosis/alkalosis?

Answer 32

Metabolic acidosis: Decreased [HCO3-] and pH | Metabolic alkalosis: Increased [HCO3-] and pH

Question 33

What are the characteristics of respiratory acidosis/alkalosis?

Answer 33

Respiratory acidosis: Increased pCO2 and decreased pH | Respiratory alkalosis: Decreased pCO2 and increased pH

Question 34

What is the compensatory response to metabolic acidosis?

Answer 34

Hyperventilation to decrease pCO2 which decreases [H+] and increases pH Increased HCO3- reabsorption and production

Question 35

What is the compensatory response to metabolic alkalosis?

Answer 35

Hypoventilation to increase pCO2 which increases [H+] and decreases pH Increased HCO3- excretion

Question 36

What is the compensatory response to respiratory acidosis?

Answer 36

Acute: - Intracellular buffering (CO2 enters cell and into H+ + HCO3- via carbonic anhydrase, H+ is neutralised by proteins so net gain of HCO3-, HCO3- is transported back to blood to help with decreasing pH) Chronic: - Increased HCO3- reabsorption and production - Increased excretion of H+/NH4+

Question 37

What is the compensatory response to respiratory alkalosis?

Answer 37

Acute: - Intracellular buffering (H2CO3 --> H+ + HCO3-) backwards reaction increasing carbonic acid so less HCO3- Chronic: - Decrease reabsorption and production of HCO3-