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

1
Q

What is osmolarity?

A

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

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2
Q

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

A

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

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3
Q

What is osmotic pressure proportional to?

A

Osmotic pressure ∝ No. of solute particles

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4
Q

How is body fluid distributed?

A
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5
Q

What is transcellular fluid?

A

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.

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6
Q

What are the unregulated sources of water loss?

A

Sweat
Faeces
Vomit
Water evaporation from respiratory lining and skin

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7
Q

What are the regulated sources of water loss?

A

Renal regulation - urine production

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8
Q

Outline renal regulation of water

A

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

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9
Q

How does osmolarity change within the medulla?

A

The deeper into the medulla, the higher the osmolarity

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10
Q

What is required for the movement of water?

A

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

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11
Q

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

A

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

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12
Q

Where is the majority of water reabsorbed?

A

67% water absorbed in the PCT

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13
Q

Where in the nephron is water reabsorbed?

A

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

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14
Q

What is countercurrent multiplication?

A

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.

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15
Q

Outline the process of countercurrent multiplication in more detail

A

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.

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16
Q

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

A

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

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17
Q

Summarise urea recycling

A

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.

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18
Q

What is the first step in urea recycling?

A

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.

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19
Q

Why is urea recycled into the medullary interstitium?

A

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

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20
Q

What is the role of vasopressin in urea recycling?

A

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

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21
Q

Give a brief overall view of urea recycling (diagram)

A
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22
Q

What is ADH?

A

Protein hormone
Promotes water reabsorption from the collecting duct

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23
Q

What factors stimulate ADH production and release?

A

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

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24
Q

What factors inhibit ADH production and release?

A

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

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25
Q

What detects changes in plasma osmolarity?

A

Osmoreceptors in the hypothalamus

26
Q

What is the threshold for BP change to stimulate baroreceptors?

A

5-10% change require for detection by baroreceptors

27
Q

Outline the mechanism of action of ADH

A

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

28
Q

At what levels of ADH does diuresis occur?

A

Zero/small

29
Q

What is diuresis?

A

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

30
Q

What is occurring in the thick ascending limb during diuresis?

A

Active reabsorption of NaCl makes the tubular fluid hypoosmotic

31
Q

What is occurring in the DCT during diuresis?

A

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

32
Q

What is occurring in the collecting duct during diuresis

A

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

33
Q

What are the ADH levels in antidiuresis?

A

High

34
Q

What are the effects of ADH on sodium reabsorption?

A

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

35
Q

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

A

Decreased/negligent production and release of ADH

Polyuria
Polydipsia

External ADH

36
Q

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

A

Increased production and release of ADH

Hyperosmolar urine
Hypervolemia
Hyponatremia

Non-peptide inhibitor of ADH receptor
(conivaptan & tolvaptan)

37
Q

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

A

Less/mutant AQP2
Mutant V2 receptor

Polyuria
Polydipsia

Thiazide diuretics + NSAIDs

38
Q

Explain the concept of acid-base balance

A

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

39
Q

How is metabolic acid neutralized?

A

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

40
Q

What is the extracellular fluid concentration of bicarbonate ions?

A

~350mEq OR 24mEq/L

41
Q

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

A

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

42
Q

What is the role of carbonic anhydrase?

A

Aids in the production of bicarbonate

43
Q

What is the Henderson-Hasselbalch equation?

A
44
Q

What equation is used to calculate H+ concentration?

A
45
Q

Where is bicarbonate reabsorbed in the nephron?

A

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

46
Q

How are acid-base disorders categorised?

A

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

47
Q

What are the roles of alpha and beta intercalated cells?

A

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

48
Q

How is bicarbonate reabosrbed in alpha-intercalated cells?

A

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

49
Q

How are new bicarbonate ions produced?

A

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)

50
Q

What are the characteristics of metabolic acidosis?

A

↓ [HCO3-]
↓ pH

51
Q

What are the compensatory responses to metabolic acidosis?

A

↑ Ventilation
↑ [HCO3-] reabsorption and production

52
Q

What are the characteristics of metabolic alkalosis?

A

↑ [HCO3-]
↑ pH

53
Q

What are the compensatory responses to metabolic alkalosis?

A

↓ Ventilation
↑ [HCO3-] excretion

54
Q

What are the characteristics of respiratory acidosis?

A

↑ PCO2
↓ pH

55
Q

What are the compensatory responses to respiratory acidosis

A

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

56
Q

What are the characteristics of respiratory alkalosis?

A

↓ PCO2
↑ pH

57
Q

What are the compensatory responses to respiratory alkalosis?

A

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

58
Q

What is intracellular buffering?

A

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

59
Q

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

A

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

60
Q

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

A

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