Renal Physiology & Disease - Clinical Correlations (Regner)

Question 1

1) What is a typical daily water intake?
2) What is a typical daily urine output?
3) In what ways is water lost other than urine output?

Answer 1

1) Input: 1.0-1.5 L/d
2) Urine Output: 1.0-1.5 L/d (aside from insensible losses, must match input!)
3) Insensible Losses: Stool, Sweat, Pulmonary

Question 2

In what two major ways does the hypothalamus act to maintain isotonicity in the body?

How does the hypothalamus sense changes in tonicity?

Answer 2

1) Sensation of thirst is increased during hypertonicity and decreased during hypotonicity.
2) ADH release is increased during hypertonicity and decreased during hypotonicity.

The hypothalamus contains osmoreceptors.

Question 3

Describe the osmolarity of the tubular fluid as it progresses through the nephron:

1) Proxmial tubule
2) Loop of Henle
3) Distal tubule
4) Collecting tubule & duct

How does ADH affect the answer to #4?

Answer 3

1) Essentially isotonic (300 mOsm/L)
2) Becomes increasingly hypertonic through the descending segment, deeper into the renal medulla, (up to 1200 mOsm/L), and then increasingly hypotonic as the loop ascends back toward the renal cortex, eventually dropping to 100-200 mOsm/L.
3) ~100-300 mOsm/L
4) Anywhere from 50 to 1200 mOsm/L; ADH increases the tonicity of the tubular fluid (toward the 1200 end) in order to retain water.

Question 4

The concentration of what ion primarily determines ECF tonicity? Why?

What is the normal serum concentration range of this ion?

Answer 4

Na⁺, because it is the major ion of the ECF. Ingested fluid must enter the ECF before it can travel into other compartments.

Normal serum Na⁺ is 135-145 mEq/L.

Question 5

What are the clinical manifestations of hyponatremia?

Answer 5

Hyponatremia:

• Nausea / Vomiting
• Weakness
• Lethargy
• Headache
• Seizures
• Respiratory Depression
• Death

Question 6

Name 4 non-pharmaceutical conditions that can lead to innapropriate ADH secretion and disturbed water balance.

Answer 6

1. Cancer (e.g. small cell lung)
2. CNS disease
3. Pulmonary disease
4. HIV

Question 7

Name 3 types of drugs that can lead to innapropriate ADH secretion and disturbed water balance.

Answer 7

1. Narcotics
2. Antiemetics
3. SSRIs

Question 8

What water-balance related conditions could be caused by innappropriate elevation of ADH?

Answer 8

Hypoosmolarity, and specifically Hyponatremia

Question 9

What is a normal GFR?

Name three ways in which GFR can be calculated/estimated.

Can results from these three methods be directly compared?

Answer 9

Normal GFR: 90-125 mL/min

Serum creatinine and its clearance can be used to estimate the GFR.

1) GFR = 100/serum creatinine
2) GFR = CrCl = (U_Cr x UF)/P_Cr
3) GFR = CrCl = ((140-age) x weight (kg))/(P_Cr x 72), x0.85 if female (Cockcroft-Gault equation)

Results from these methods will not always agree. Use caution in assuming the GFR from one calculation.

Question 10

1) What compound is considered the gold standard for measuring GFR?
2) Why is it more accurate than creatinine?
3) What is the advantage to using creatinine?

Answer 10

1) Inulin
2) Some creatinine secretion occurs in the nephron, so creatinine clearance will tend to overestimate the GFR. Also, because inulin is not a natural product of the body, its serum concentration can be precisely known (as a known amount is infused).
3) Creatinine is a natural product of the body, whereas inulin requires an infusion. Creatinine has been shown to be accurate enough under most circumstances.

Question 11

What is the use of Blood Urea Nitrogen (BUN) in assessing kidney function?

Answer 11

BUN is less accurate than creatinine in estimating the GFR, as it can vary due to protein intake, catabolic rate, and tubular reabsorption.

However, BUN is useful in conjunction with creatinine in the differential diagnosis of renal disease.

Question 12

Why is creatinine useful in measuring GFR again?

Answer 12

Because it is only filtered and not secreted or reabsorbed (mostly).

Thus, it simplifies the renal input = output equation to amount filtered (the GFR) = amount excreted (measurable creatinine).

Question 13

What factors can cause inaccuracy in serum creatinine based GFR estimates?

Answer 13

Extremes of:

• Age
• BMI
• Muscle Mass

Question 14

How does baroreceptor activation help to correct a loss in BP?

(I mean the activation of a baroreceptor response due to a loss in BP, not an increased rate of baroreceptor firing due to a gain in BP. “Baroreceptor Activation” was used in the former context in this lecture.)

Answer 14

Baroreceptor activation leads to increased sympathetic tone, which mediates:

• Increased cardiac contractility & HR
• Increased venous return
• Increased arterial resistance
• Increased renin secretion

Question 15

What does activation of renal sympathethic nerves accomplish?

Answer 15

• Increased renin release
• Increased Na⁺ reabsorption

Activation of renal sympathetics → mechanisms that promote BP increase

Question 16

How does Ang II mediate increased reabsorption of Na⁺ in the proximal tubule?

Answer 16

Ang II binds the AT₁ receptor, leading to increased activity of Na⁺ transport channels, including:

• BL side Na⁺/H⁺ exchanger
• Apical side Na⁺/K⁺ ATPase
• Apical side Na⁺/HCO₃^- symporter

(BL side = tubular lumen side)

Question 17

How does Aldosterone mediate increased reabsorption of Na⁺ in the cortical collecting duct principal cells?

Answer 17

Aldosterone increases the number of Na⁺ transport channels, including:

• luminal Na⁺ channels (?)
• BL side Na⁺/K⁺ ATPases

Question 18

Name three mechanisms that stimulate Ang II formation

Answer 18

Ang II formation is dependent upon renin secretion, and therefore is stimulated by:

1. Baroreceptor activation
2. Macula densa activation
3. Increased renal sympathetic tone

Question 19

How does ADH mediate increased water reabsorption from the distal tubules, collecting tubules, and collecting ducts?

Answer 19

AVP binds a V₂ receptor that activates G_s, leading to increased cAMP and thus PKA. PKA-mediated protein phosphorylation stimulates the translocation of Aquaporin-2 (AQP-2) channels from cytoplasmic vesicles into the BL cell wall.

Question 20

What clinical lab findings would be seen with enchanced tubular Na⁺ and H₂O reabsorption?

Answer 20

• Low urine Na⁺
• Low FENa⁺ (Fractional Excretion of Na⁺)
• Elevated urine osmolarity

Question 21

What is the purpose of parathyroid hormone (PTH)?

How does it accomplish this purpose?

Answer 21

PTH is released to increase serum Ca²⁺ levels when said levels are low.

It does this via:

• Increased Vitamin D₃ activation
  
  • Causes increased intestinal Ca²⁺ reabsorption
• Increased renal Ca²⁺ absorption
• Increased Ca²⁺ release from bone

Question 22

How can kidney disease cause secondary hyperparathyroidism?

What complications can arise from this secondary hyperparathyroidism?

Answer 22

Decreased kidney function can lead to:

• Increased serum PO₄ (insufficient excretion), which chelates Ca²⁺
• Decreased synthesis of 1,25 Vitamin D (Calcitriol) by proximal tubule cells, leading to decreased Ca²⁺ absorption from the intestine

Together, these factors cause a decrease in serum Ca²⁺, so PTH is released to restore these levels.

This can lead to excessive bone turnover and extraosseus calcification.