Disorders of the Proximal Tubule

Question 1

What important vitamin is synthesized to final active form in the proximal tubule?

Answer 1

Vitamin D

Question 2

What are the major substrates reabsorbed in the PT?

Answer 2

Na
Water
K
Phosphorus
Calcium
Glucose
Urea

Question 3

Why is the PT highly susceptible to ischemia?

Answer 3

High ATP demand due to active transport Na/K

Polarized cell structures requires ATP to maintain cytoskeleton attachments and shape

Question 4

What are the common causes of generalized PT dysfunction?

Answer 4

Energy generation issues

Question 5

Describe hereditary renal glucosuria: inheritance, defect, and effects

Answer 5

AR
SGLT2 glucose transporter mutation
Mild to severe glucosuria due to inability to reabsorb glucose

Question 6

What is a SGLT2 inhibitor useful in diabetes?

Answer 6

Canagliflozin

Question 7

Describe cystinuria: inheritance, defect, effects

Answer 7

AR
Mutated AA transporters
Leads to cystine crystals

Question 8

What is X-linked hypophosphatemia - mutation, S/S

Answer 8

PHEX mutation leads to increased FGF-23 which downregulates activity of phosphate/Na symporter

Presents as rickets in kids and osteomalacia in adults

Characterized by: urinary phosphate wasting, low serum Phos

Question 9

What is the defect in AD hypophosphatemic rickets?

Answer 9

FGF-23

Question 10

What is the defect in AR hypophosphatemic rickets?

Answer 10

Mut leading to inc FGF-23 or mut in Na/Pi transporter

Question 11

What is the acquired cause of defective phosphate reabsorption we talked about?

Answer 11

Oncogenic hypophosphatemic osteomalacia - increased FGF-23 production by tumors

Question 12

What is Hartnup Disease?

Answer 12

Defective neutral amino acid transporter?

Question 13

What is Vitamin D-dependent rickets type 1?

Answer 13

Mutated 1a-hydroxylase leading to hypophosphatemia and rickets

Question 14

What is Fanconi syndrome?

Answer 14

usually acquired - glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed

Question 15

What are the clinical manifestations of Fanconi syndrome?

Answer 15

Polyuria/polydipsia
Volume depletion
Arrythmias (low K)
Proteinuria
Growth retardation
Rickets
Renal stones (Ca excretion)

Question 16

What is the major cause of inherited Fanconi syndrome?

Answer 16

Cystinosis

Question 17

What are the major acquired causes of Fanconi syndrome?

Answer 17

Tenofovir use and other retrovirals
Lead
Multiple myeloma

Question 18

What is the treatment for cystinosis

Answer 18

Cysteamine, which binds cysteine in lysosomes and depletes it

Question 19

What are the two effects of ADH on AQP2?

Answer 19

Short-term (minutes) insertion of pores into luminal surface from cytosolic stores

Long-term (>24h) increased synthesis of AQP2

Question 20

What is the C osm clearance (not form?)

Answer 20

Water needed to excrete solutes at the concentration of solutes in plasma

Question 21

What is C water?

Answer 21

The extra water cleared on top of the obligatory amount of water needed based on plasma osmolarity

Question 22

Cwater=

Answer 22

V * (1-(Uosm/Posm)

Question 23

What is the cause of hyposmolar hyponatremia?

Answer 23

Impaired urinary dilution mechanisms

true hyponatremia

Question 24

What are the three places in the nephron that can lead to inability to dilute urine?

Answer 24

Glomerulus issues from age/HF/cirrhosis
Na/Cl reabsorption reduced by diuretics
Upregulation of AQP2 by ADH (SIADH)

all cause lots of water reabsorption

Question 25

What is the major cause of SIADH acc to her?

Answer 25

medications

Question 26

Just go over the last 10 or so slides cause they’re dense and good summary of urine concentration and dilution

Answer 26

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