Regulation of Sodium and Water

Question 1

What are the functions of water and fluids in the body?

Answer 1

• Dissolve and transport substances, account for blood volume, help maintain body temperature, protect and lubricate tissue, participate in chemical reactions
• To maintain water balance, a person must consume at least the same amount lost each day to avoid life-threatening losses

Question 2

How do we consume water?

Answer 2

• Food eaten, air temperature, humidity, altitude, activity level
• Men need around 13 cups and women need around 9 cups
• Ingestion of liquids and food

Question 3

How do we lose water?

Answer 3

1. Urination and feces (water loss through kidneys) -> cannot be completely shut down
2. Skin: perspiration (temperature and humidity)
3. Lungs: loss during respiration
   - Loss of water by perspiration and respiration is insensible water loss (unregulated)

Question 4

Osmotic Pressure

Answer 4

• Hormonal regulation of urine production is regulated by osmotic pressure of plasma
• Plasma osmolality: largely dependent on sodium concentration (sodium indirectly controls the amount of water in the body)
• Movement of water across the biological membranes is dependent on the osmotic pressure differences between the intracellular fluid (ICF) and extracellular fluid (ECF)
• Osmotic pressure of EFC in normal state is due to sodium ions (equal to osmotic pressure of ICF which is due to potassium ions)
• 285-295 milliosmoles/kg

Question 5

Osmolarity

Answer 5

Number of moles (or millimoles) per liter of solution

Question 6

Osmolality

Answer 6

• Number of moles (or millimoles) per kg of solvent
• If solvent is pure water there is almost no difference between osmolality and osmolarity
• Biological fluids
• Osmolality of intra and extracellular fluid is the same, but there is marked difference in the solute content

Question 7

How is plasma osmolality computed?

Answer 7

• From concentrations (mmol/L) of sodium, potassium, urea, and glucose: 2(Na+) + 2(K+) + Urea + Glucose
• Factor of 2 is used for Na+ and K+ ions to account for the associated anion concentration
• Plasma Na+ is predominant: plasma osmolality (mmol/kg) = 2 x plasma Na+ (mmol/L)

Question 8

Nephron

Answer 8

• Function: regulate osmolality
  1. Filtration: ions and small molecules
  2. Reabsorption: selective reabsorption of ions and molecules happens at the ascending limb of loop of Henle
• Comprised of eight sequential structural components that collectively facilitate the overall filtering of the blood:
  1. Bowman’s capsule -> surrounds the glomerulus
  2. Proximal convoluted tubule
  3. Descending limb of Henle’s loop
  4. Loop of Henle
  5. Ascending limb of Henle’s loop
  6. Distal convoluted tubule
  7. Collecting duct
  8. Urine bladder

Question 9

Glomerulus

Answer 9

• Group of capillaries interposed between two arterioles (afferent and efferent)
• Filtration

Question 10

Podocytes

Answer 10

• Podocytes in the Bowman’s capsule form pores which prevents passage of large molecules into the nephron tubule
• Filtration

Question 11

Renal Tubule

Answer 11

• Reabsorption
• Single layer of epithelial cells
• Fluid flows through the tubule in one direction (Bowman’s capsule -> collecting duct system -> ureter)

Question 12

Juxtaglomerular Cells (JG)

Answer 12

• Associated with afferent arteriole and can produce renin
• Renin is an enzyme that cleave angiotensinogen to angiotensin I

Question 13

Macular Densa Cells

Answer 13

• Salt sensors that generate paracrine signals to control kidney function
• Blood flow, glomerular filtration, renin release
• Detect changes in sodium and secrete:
  1. Vasopressor that can bind to receptors on afferent arteriole decreasing glomerular filtration rate -> reduced filtration (when sodium is increased)
  2. Signals to the efferent arteriole to increase water and salt reabsorption (when blood pressure is decreased or sodium is decreased)

Question 14

Explain how antidiuretic hormone (ADH/vasopressin) is used to regulate sodium and water balance.

Answer 14

1. Plasma osmolality increases (due to Na+)
2. Osmoreceptors of hypothalamus are stimulated
3. ADH secretion -> neural tract -> posterior pituitary -> bloodstream -> kidney
4. Increases water reabsorption by the renal tubules
5. Plasma osmolality decreases

Question 15

Explain how ADH is secreted.

Answer 15

• Secreted from supraoptic and PVN
• Neurons extend to posterior pituitary
• Released directly into the bloodstream

Question 16

How does ADH signal?

Answer 16

• Signals via GPCR (Avpr2 or V2) in the kidneys
  1. ADH binds to V2 on cells of distal convoluted tubule
  2. Binding -> activates adenylate cyclase -> increases cAMP
  3. cAMP activates PKA
  4. PKA phosphorylates aquaporin-2 (AQP2)
  5. Phosphorylated AQP2 moves into the apical membrane
  6. AQP2 is a water channel and allows water back into the cell

Question 17

Aldosterone

Answer 17

• Mineralocorticoid
• produced in the zona glomerulosa of the adrenal cortex
• Regulates Na+/K+ and Na+/H+ exchange in the renal tubule
• Sodium retention
• Binds to MR in the cell cytosol -> receptor translocate to the nucleus -> stimulates the production of ion channels
• Also acts in the colon to increase sodium and water retention

Question 18

Renin

Answer 18

• When ECF volume falls -> renal plasma flow decreases -> release of renin from juxtaglomerular cells
• 30 AA zinc containing enzyme
• Substrate is the glycoprotein angiotensinogen (produced by the liver)
• Hydrolyzes the leu-leu bond of angiotensinogen to generate biologically inactive decapeptide angiotensin I

Question 19

Angiotensin-converting enzyme (ACE)

Answer 19

• Angiotensin I -> angiotensin II
• Zinc metalloprotein
• Produced by the pulmonary endothelium (lungs) and kidney
• Inactivates bradykinin (potent vasodilator)

Question 20

Angiotensin II

Answer 20

• Most potent vasoconstrictive agent known
• Also stimulates aldosterone synthesis and secretion

Question 21

Explain the renin-angiotensin-aldosterone system.

Answer 21

1. Liver produces angiotensinogen
2. Renin (from the kidney) converts angiotensinogen to angiotensin I
3. ACE (from the lungs and kidney) converts angiotensin I to angiotensin II
4. Angiotensin II -> kidney -> constricts glomerular efferent arteriole and increases Na+/H+ exchanger activity
5. Angiotensin II -> posterior pituitary -> ADH secretion
6. Angiotensin II -> vascular smooth muscle -> hypertension
7. Angiotensin II -> hypothalamus -> stimulates thirst
8. Angiotensin II -> adrenal cortex -> aldosterone secretion

Question 22

What factors stimulate renin secretion?

Answer 22

1. Decreased blood pressure
2. Decreased sodium delivery to the macula densa
3. Increased sympathetic tone

Question 23

Atrial Natriuretic Protein (ANP)

Answer 23

• Secreted by atrial cells of the heart in response to volume expansion or increased blood pressure
• Stimulates the excretion of sodium in the urine (natriuresis)
• Hormone antagonist to the angiotensin pathway
• Decreases blood volume and pressure by: increasing filtration rate, decreasing reabsorption of sodium by nephrons, inhibiting renin, aldosterone, and ADH release

Question 24

What are the effects of aldosterone?

Answer 24

Causes the nephron distal tubules to reabsorb more sodium and water -> increases blood volume

Question 25

What are the effects of ADH?

Answer 25

- Mediates insertion of aquaporins into nephron collecting duct cells -> more water is reabsorbed into the blood - Increases sodium reabsorption in the medulla of the kidney

Question 26

Hypertonic

Answer 26

Effective osmolality is increased -> body fluid is called hypertonic

Question 27

Hypotonic

Answer 27

Osmolality is decreased -> body fluid is called hypotonic

Question 28

Explain the isotonic contraction (loss) of ECF.

Answer 28

- Results from loss of fluid that is isotonic with plasma - Typically caused by loss of GI fluid - Equivalent amounts of sodium and water are lost -> plasma sodium is often normal - Hypovolemia -> reduce renal blood flow - Renin-aldosterone system is activated -> selective sodium reabsorption occurs - ADH secretion -> reabsorption of equivalent amounts of water

Question 29

Hypotonic Contraction

Answer 29

- Predominant sodium depletion - Infusion of fluids with low sodium content like dextrose -> hypo-osmolality -> inhibits ADH secretion -> water loss (plasma sodium tends to return to normal) - Deficiency of aldosterone in Addison's disease -> decreased sodium retention -> lowers osmolality and inhibits ADH -> contraction of ECF volume -> hypovolemia -> ADH secretion -> further hemodilution and hyponatremia

Question 30

Hypotonic Expansion

Answer 30

- Predominant water excess results only when the normal homeostatic mechanism fails - Water retention either due to glomerular dysfunction, ADH excess or excess intake - Water excess will lower osmolality - Inhibition of ADH secretion and excretion of large volumes of dilute urine can improve - Hyponatremia persists due to inhibition of aldosterone secretion by expanded ECF volume - Cellular overhydration

Question 31

Hypertonic Contraction

Answer 31

- Water depletion - Caused by diarrhea, vomiting, excess sweating, diabetes insipidus (ADH deficiency) - Hypernatremia present with high plasma osmolaity - Volume depletion -> reduce renal blood flow and stimulates aldosterone secretion -> further sodium retention -> hypertension - Increase is osmolality -> thirst and increase water intake

Question 32

Hypertonic Expansion

Answer 32

- Conn's syndrome (too much aldosterone) and Cushing's syndrome (too much CORT) - Excess mineralocorticoid (or MR signaling) -> produce sodium retention -> increase in plasma osmolality -> increase ADH secretion -> restore osmolality - Aldosterone will cause sodium retenton - Associated with hypokalemia (low potassium) -> metabolic alkalosis