nephron physiology

Question 1

copy out normal nephron physiology

Answer 1

page 528)

Question 2

Fanconi syndrome

Answer 2

reabsorptive defect in the PCT
associated with increase excretion of nearly all amino acids, glucose, HCO3-, and PO4 3-. may result in metabolic acidosis (proximal renal tubular acidosis- remember, in fanconi syndrome, we don’t resorb HCO3-).
causes include hereditary defects (Wilson disease- copper accumulates in the kidney and causes damage), ischemia, and nephrotoxins/drugs
remember, kidneys put out FABulous Glittering Liquid: fanconi is first, bartter is second, gitelman is third, liddle is fourth

Question 3

Bartter syndrome

Answer 3

reabsorptive defect in the thick ascending loop of Henle.
autosomal recessive. affects the Na/K/2Cl transporter. causes hypokalemia and metabolic alkalosis with hypercalciuria.
(alkalosis: this defect causes vol depletion –> incr. aldosterone and incr. distal Na delivery –> increased Na reabsorption in collecting duct principle cells. to compensate, we lose K in the collecting duct (hypokalemia) and we excrete more H in the collecting duct alpha cells (alkalosis)

Question 4

Gitelman syndrome

Answer 4

reabsorptive defect in the NaCl in the DCT. autosomal recessive. less severe than bartter syndrome. leads to hypokalemia and metabolic alkalosis, but without hypercalciuria (not sure why mechanistically, but I know that gitelman is a relatively “good” defect and bartter is a relatively “bad” defect).

Question 5

Liddle syndrome

Answer 5

last one! This causes INCREASED Na resorption in the distal and collecting tubules (increased activity of epithelial Na channel).
autosomal dominant.
causes hypertension, hypokalemia, metabolic alkalosis, decreased aldo. treatment: amiloride (blocks the Na channel in the collecting tubule.

Question 6

relative concentrations along proximal tubles: think about Na, Cl, creatinine, inulin, PAH, urea, phosphate, HCO3, amino acids, glucose

Answer 6

this could show up as graph interpretation. the graph would have percent distance along proximal tubule on the x axis and TF/P on the y axis (TF is tubular fluid conc.; P is plasma fluid conc.). very positive linear slope suggests secretion without much resorption (PAH, creatinine). inulin slope also increases (its amount is the same but its concentration will increase as water is absorbed in the PCT). Cl resorption initially occurs more slowly than Na resorption; thus, it will have a positive slope at first (water is resoprbed more- concentration will increase), then it will plateau. Na is close to 1 all the time- it is resoprbed at about the same rate as water.
Pi and HCO3 have negative, non-linear slopes. amino acids and glucose have the most negative slopes.

Question 7

renin-angiotensin system: what induces release of renin? what regulates angiotensin converting enzyme? what does angiotensin II do?

Answer 7

renin is released when BP is low, low delivery of Na to the macula densa, high sympathetic tone. it is released by juxtoglomerular cells.
ACE breaks down bradykinin (mediator of pain and vasodilation).
angiotensin:
1. peripheral vascoconstriction
2. preferential constriction of the efferent arteriole of the glomerulus to preserve GFR (no net loss of Na/water because of compensatory Na resorption in the proximal and distal nephron)
3. induce release of aldosterone from the adrenals (aldo will act in the collecting duct to increase Na channels and Na/K ATPase; enhances K and H excretion)
4. directly increase Na/H exchanger in the PCT (can permit a contraction alkalosis)
5. increase ADH release from the posterior pituitary to increase water resorption
6. stiumate thirst
angiotensin also limits bradycardia that would normally accompany its pressor effects

Question 8

atrial naturetic peptide

Answer 8

released from atria in response to increased volume. may act as a check on the renin-angiotensin-aldosterone system. relaxes vascular smooth muscle via cGMP, increases GFR, decreases renin.
it will increase GFR (dilated afferent arteriole?) without a compensatory Na resoption in the distal nephron. this causes net Na and water loss.

Question 9

juxtoglomerular apparatus. What is a drug that may decrease activity of the JGA?

Answer 9

consists of JG cells (modifed smooth muscle of the afferent arteriole) and the macula densa (NaCl sensor in the DCT). JG cells secrete renin in response to decr. renal BP, decr. NaCl delivery to the DCT, and increased sympathetic tone (beta 1). beta blockers decrease JGA activity by blocking beta 1 receptors.

Question 10

What are the endocrine functions of the kidney (4)? What cells perform these endocrine functions?

Answer 10

1. interstitial cells release EPO in response to hypoxia
2. convert 25-OH vitamin D to 1,25 OH vitamin D using 1 alpha hydroxylase. this happens in the PCT.
3. JG cells secrete renin
4. prostaglandins: paracrine secretion vasodilates the afferent arterioles to increase renal blood flow. NSAIDs may block this and cause acute renal failure.

Question 11

What does PTH do in the kidney?

Answer 11

secreted in response to low plasma calcium, high plasma PO4 3-, or low 1,25 (OH)1 vitamin D.
causes increased calcium resorption in the DCT, decreased phosphate resorption in the PCT, and increased 1,25 (OH)2 vitamin D production (increased 1 alpha hydroxylase activity).