💧Urology💧- Regulation of Water & Acid-Base Balance

Question 1

What is osmolarity?

Answer 1

Osmolarity = Concentration x No. of dissociated particles
= Osm/L OR mOsm/L

Question 2

Calculate the osmolarity for 100 mmol/L glucose and 100mmol/L NaCl

Answer 2

Osmolarity for glucose = 100 x 1 = 100 mOsm/L
Osmolarity for NaCl = 100 x 2 = 200 mOsm/L

Question 3

What is osmotic pressure proportional to?

Answer 3

Osmotic pressure ∝ No. of solute particles

Question 4

How is body fluid distributed?

Answer 4

Question 5

What is transcellular fluid?

Answer 5

Transcellular fluid is a component of extracellular fluid that is found in specialized compartments, separated from other extracellular fluids by epithelial layers. These fluids are typically involved in lubrication, cushioning, or specific physiological functions.

Question 6

What are the unregulated sources of water loss?

Answer 6

Sweat
Faeces
Vomit
Water evaporation from respiratory lining and skin

Question 7

What are the regulated sources of water loss?

Answer 7

Renal regulation - urine production

Question 8

Outline renal regulation of water

Answer 8

Note [Na+] refers to concentration of sodium, not amount

Question 9

How does osmolarity change within the medulla?

Answer 9

The deeper into the medulla, the higher the osmolarity

Question 10

What is required for the movement of water?

Answer 10

Since water is reabsorbed through the passive process of osmosis, it requires a gradient

Question 11

What conditions are needed for water reabsorption to occur in the LOH and collecting duct?

Answer 11

The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and Collecting duct

Question 12

Where is the majority of water reabsorbed?

Answer 12

67% water absorbed in the PCT

Question 13

Where in the nephron is water reabsorbed?

Answer 13

PCT (majority)
Passively in the descending LOH
Variable amounts of water in the collecting duct

Question 14

What is countercurrent multiplication?

Answer 14

Countercurrent multiplication is the process in the loop of Henle where active reabsorption of sodium and chloride in the thick ascending limb creates an osmotic gradient in the medullary interstitium. This gradient allows passive water reabsorption in the thin descending limb, concentrating the tubular fluid.

Question 15

Outline the process of countercurrent multiplication in more detail

Answer 15

Initial Conditions (A):
The osmolarity of the fluid in both limbs and the interstitium starts at ~300 mOsm/L.
There is no gradient yet.
Active Salt Reabsorption (B):
The thick ascending limb actively transports NaCl into the interstitium.
The ascending limb is impermeable to water, so osmolarity in the ascending limb decreases (e.g., to 200 mOsm/L), while the interstitial fluid becomes more concentrated (e.g., to 400 mOsm/L).
Passive Water Reabsorption (C):
The thin descending limb is permeable to water but not to solutes.
Water moves out of the descending limb into the hyperosmotic interstitium, increasing the tubular osmolarity in the descending limb (e.g., to 400 mOsm/L).
Gradient Amplification (D to F):
With continuous flow and repeated active salt pumping and water movement, the osmolarity gradient is progressively amplified.
The medullary interstitium becomes increasingly concentrated (up to ~1200 mOsm/L at the tip of the loop), and tubular fluid osmolarity varies along the loop.

Question 16

What is meant when urea is described as an “ineffective osmole”?

Answer 16

Urea can diffuse easily across most cell membranes with the help of urea transporters.
As a result, urea concentrations equilibrate between intracellular and extracellular compartments, minimizing any osmotic gradient it might create

Question 17

Summarise urea recycling

Answer 17

Urea recycling involves urea reabsorption in the collecting duct via UT-A1 and UT-A3 transporters, enhanced by vasopressin. Recycled urea contributes to the medullary interstitium’s high osmolarity, supporting water reabsorption and urine concentration. This process minimizes water loss and is essential for maintaining the osmotic gradient for concentrated urine production.

Question 18

What is the first step in urea recycling?

Answer 18

Thin Descending Limb: Urea enters the nephron from the medullary interstitium via UT-A2 transporters.
Urea travels through the nephron to the collecting duct, where it is reabsorbed into the medullary interstitium through UT-A1 (apical membrane) and UT-A3 (basolateral membrane) transporters.

Question 19

Why is urea recycled into the medullary interstitium?

Answer 19

Recycled urea contributes to the high osmolarity of the medullary interstitium (600 mmol/L), which is essential for water reabsorption and urine concentration

Question 20

What is the role of vasopressin in urea recycling?

Answer 20

Vasopressin (ADH) increases the expression of UT-A1 and UT-A3 in the collecting duct, enhancing urea reabsorption

Question 21

Give a brief overall view of urea recycling (diagram)

Answer 21

Question 22

What is ADH?

Answer 22

Protein hormone
Promotes water reabsorption from the collecting duct

Question 23

What factors stimulate ADH production and release?

Answer 23

Increase plasma osmolarity
Hypovolemia - decreased blood pressure
Nausea
Angiotensin II
Nicotine

Question 24

What factors inhibit ADH production and release?

Answer 24

Decreased plasma osmolarity
Hypervolemia - increased blood pressure
Ethanol
Atrial natriuretic peptide (ANP)

Question 25

What detects changes in plasma osmolarity?

Answer 25

Osmoreceptors in the hypothalamus

Question 26

What is the threshold for BP change to stimulate baroreceptors?

Answer 26

5-10% change require for detection by baroreceptors

Question 27

Outline the mechanism of action of ADH

Answer 27

Binds to V2 receptor G-protein reaction cascade Activates adenylate cyclase, converts ATP to cAMP cAMP promotes activity of protein kinase A Leads to insertion of AQP2 into apical membrane

Question 28

At what levels of ADH does diuresis occur?

Answer 28

Zero/small

Question 29

What is diuresis?

Answer 29

Diuresis refers to the increased production of dilute urine, typically due to minimal or absent Antidiuretic Hormone (ADH)

Question 30

What is occurring in the thick ascending limb during diuresis?

Answer 30

Active reabsorption of NaCl makes the tubular fluid hypoosmotic

Question 31

What is occurring in the DCT during diuresis?

Answer 31

Sodium and chloride are actively reabsorbed via: Na⁺-Cl⁻ symporters into the tubular cells Na⁺-K⁺ ATPase pump for sodium transport into the blood

Question 32

What is occurring in the collecting duct during diuresis

Answer 32

Minimal Water Reabsorption: Low ADH prevents the insertion of AQP2 channels, so water stays in the lumen. Sodium Reabsorption: Principal cells in the collecting duct reabsorb sodium using the Na⁺-K⁺ ATPase pump, contributing to electrolyte balance

Question 33

What are the ADH levels in antidiuresis?

Answer 33

High

Question 34

What are the effects of ADH on sodium reabsorption, and which channels are affected?

Answer 34

Supports Na+ reabsorption Thick ascending limb: ↑Na+/K+/2Cl- symporter Distal convoluted tubule: ↑Na+/Cl- symporter Collecting duct: ↑Na+ channel

Question 35

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

Answer 35

Decreased/negligent production and release of ADH Polyuria Polydipsia External ADH

Question 36

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

Answer 36

Increased production and release of ADH Hyperosmolar urine Hypervolemia Hyponatremia Non-peptide inhibitor of ADH receptor (conivaptan & tolvaptan)

Question 37

What is the cause, clinical features and treatment of Nephrogenic Diabetes Insipidus?

Answer 37

Less/mutant AQP2 Mutant V2 receptor Polyuria Polydipsia Thiazide diuretics + NSAIDs

Question 38

Explain the concept of acid-base balance

Answer 38

Diet and metabolism contribute to the production of acids and bases. Acid is balanced against base, with base excreted in faeces. However, there is a net addition of metabolic acid of approximately 50–100 mEq/day, which must be neutralised

Question 39

How is metabolic acid neutralized?

Answer 39

𝐻2𝑆𝑂𝟒+2𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎2𝑆𝑂4+2𝐶𝑂2+2𝐻2𝑂 𝐻𝐶𝑙+𝑁𝑎𝑯𝑪𝑶𝟑↔𝑁𝑎𝐶𝑙+𝐶𝑂2+𝐻2𝑂

Question 40

What is the extracellular fluid concentration of bicarbonate ions?

Answer 40

~350mEq OR 24mEq/L

Question 41

What is the role of kidneys in acid-base balance?

Answer 41

Secretion and excretion of H+ Reabsorption of HCO3- Production of new HCO3-

Question 42

What is the role of carbonic anhydrase?

Answer 42

Aids in the production of bicarbonate

Question 43

What is the Henderson-Hasselbalch equation?

Answer 43

Question 44

What equation is used to calculate H+ concentration?

Answer 44

Question 45

Where is bicarbonate reabsorbed in the nephron?

Answer 45

Majority (80%) in the PCT Minor amounts in the thick ascending limb, DCT and collecting duct, in decreasing amounts

Question 46

How are acid-base disorders categorised?

Answer 46

By their primary cause Respiratory: Changes in PCO2 Metabolic: Changes in [HCO3−]

Question 47

What are the roles of alpha and beta intercalated cells?

Answer 47

⍺-Intercalated cell: HCO3- reabsorption & H+ secretion β-Intercalated cell: HCO3- secretion & H+ reabsorption

Question 48

How is bicarbonate reabosrbed in alpha-intercalated cells?

Answer 48

CO₂ diffuses into the cell and reacts with water, catalyzed by carbonic anhydrase, to form carbonic acid (H₂CO₃), which dissociates into H⁺ and HCO₃⁻ (bicarbonate) The HCO₃⁻ produced is transported into the blood through the basolateral Cl⁻/HCO₃⁻ exchanger

Question 49

How are new bicarbonate ions produced?

Answer 49

In the PCT from glutamine Ammoniogenesis Glutamine produces 2 ammonium ions and a divalent ion - produces 2 bicarbonate ions Ammonium ions must be excreted to allow net addition of HCO3- Occurs via Na+/H+ antiporter and via diffusion in the form of NH3 gas In the DCT - protons can be neutralised by another urinary buffer (e.g. phosphate)

Question 50

What are the characteristics of metabolic acidosis?

Answer 50

↓ [HCO3-] ↓ pH

Question 51

What are the compensatory responses to metabolic acidosis?

Answer 51

↑ Ventilation ↑ [HCO3-] reabsorption and production

Question 52

What are the characteristics of metabolic alkalosis?

Answer 52

↑ [HCO3-] ↑ pH

Question 53

What are the compensatory responses to metabolic alkalosis?

Answer 53

↓ Ventilation ↑ [HCO3-] excretion

Question 54

What are the characteristics of respiratory acidosis?

Answer 54

↑ PCO2 ↓ pH

Question 55

What are the compensatory responses to respiratory acidosis

Answer 55

Acute: intracellular buffering Chronic: ↑ [HCO3-] reabsorption and production

Question 56

What are the characteristics of respiratory alkalosis?

Answer 56

↓ PCO2 ↑ pH

Question 57

What are the compensatory responses to respiratory alkalosis?

Answer 57

Acute: intracellular buffering Chronic: ↓ [HCO3-] reabsorption and production

Question 58

What is intracellular buffering?

Answer 58

The process by which cells use intracellular proteins, organic phosphates (e.g., ATP), and intracellular bicarbonate to mitigate changes in pH caused by acute respiratory acidosis or alkalosis

Question 59

How does intracellular buffering work in the context of acute respiratory acidosis?

Answer 59

Intracellular proteins (e.g., haemoglobin in red blood cells) and phosphates act as buffers by binding to the excess H⁺, limiting the pH change

Question 60

How does intracellular buffering work in the context of acute respiratory alkalosis?

Answer 60

Less CO₂ enters cells, leading to a reduction in intracellular H⁺ production Buffers release H⁺ to compensate for the alkalotic shift, stabilizing intracellular pH