Disorders of the Proximal Tubule Flashcards
What important vitamin is synthesized to final active form in the proximal tubule?
Vitamin D
What are the major substrates reabsorbed in the PT?
Na Water K Phosphorus Calcium Glucose Urea
Why is the PT highly susceptible to ischemia?
High ATP demand due to active transport Na/K
Polarized cell structures requires ATP to maintain cytoskeleton attachments and shape
What are the common causes of generalized PT dysfunction?
Energy generation issues
Describe hereditary renal glucosuria: inheritance, defect, and effects
AR
SGLT2 glucose transporter mutation
Mild to severe glucosuria due to inability to reabsorb glucose
What is a SGLT2 inhibitor useful in diabetes?
Canagliflozin
Describe cystinuria: inheritance, defect, effects
AR
Mutated AA transporters
Leads to cystine crystals
What is X-linked hypophosphatemia - mutation, S/S
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
What is the defect in AD hypophosphatemic rickets?
FGF-23
What is the defect in AR hypophosphatemic rickets?
Mut leading to inc FGF-23 or mut in Na/Pi transporter
What is the acquired cause of defective phosphate reabsorption we talked about?
Oncogenic hypophosphatemic osteomalacia - increased FGF-23 production by tumors
What is Hartnup Disease?
Defective neutral amino acid transporter?
What is Vitamin D-dependent rickets type 1?
Mutated 1a-hydroxylase leading to hypophosphatemia and rickets
What is Fanconi syndrome?
usually acquired - glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed
What are the clinical manifestations of Fanconi syndrome?
Polyuria/polydipsia Volume depletion Arrythmias (low K) Proteinuria Growth retardation Rickets Renal stones (Ca excretion)
What is the major cause of inherited Fanconi syndrome?
Cystinosis
What are the major acquired causes of Fanconi syndrome?
Tenofovir use and other retrovirals
Lead
Multiple myeloma
What is the treatment for cystinosis
Cysteamine, which binds cysteine in lysosomes and depletes it
What are the two effects of ADH on AQP2?
Short-term (minutes) insertion of pores into luminal surface from cytosolic stores
Long-term (>24h) increased synthesis of AQP2
What is the C osm clearance (not form?)
Water needed to excrete solutes at the concentration of solutes in plasma
What is C water?
The extra water cleared on top of the obligatory amount of water needed based on plasma osmolarity
Cwater=
V * (1-(Uosm/Posm)
What is the cause of hyposmolar hyponatremia?
Impaired urinary dilution mechanisms
true hyponatremia
What are the three places in the nephron that can lead to inability to dilute urine?
Glomerulus issues from age/HF/cirrhosis
Na/Cl reabsorption reduced by diuretics
Upregulation of AQP2 by ADH (SIADH)
all cause lots of water reabsorption
What is the major cause of SIADH acc to her?
medications
Just go over the last 10 or so slides cause they’re dense and good summary of urine concentration and dilution
aaahhhhh
