Renal Endocrinology Flashcards
erythropoietin (EPO)
stimulates RBC production
produced by peritubular interstitial cells in cortex/outer medulla
when is EPO production upregulated
hypoxic conditions
aged RBCs have dec. O2 carrying capacity –> dec. O2 reaching kidneys –> stimulates inc. EPO production
how does RBC production depend on EPO
once hematopoietic stem cells commit to erythroid lineage they express an EPO receptor
if EPO binds: erythroblasts survive and differentiate
(hypoxic conditions)
if EPO does not bind: erythroblasts undergo apoptosis
(normoxic conditions)
what is EPO expression dependent on
hypoxic conditions
allows survival of HIFs
hypoxia-inducible factors (HIFs) in hypoxic conditions
transcription factors accumulate –> cross into nucleus of peritubular cells –> induce EPO expression
hypoxia-inducible factors (HIFs) in normoxic conditions
HIFs get hydroxylated –> targets them for ubiquination –> gets degraded by proteasomes
where is the ONLY place where calcitriol is produced
kidneys
inactive vitamin D must travel to kidneys to get hydroxylated by 1a-hydroxylase to form active vitamin D3 (calcitriol)
what stimulates 1a-hydroxylase action
PTH
hypophosphatemia
hypocalcemia
what inhibits 1a-hydroxylase action
calcitriol (negative feedback)
FGF-23
function of calcitriol
increase Ca and PO4 reabsorption
where is FGF-23 produced
osteocytes in bone
what does FGF-23 bind to
binds to FGF-23 & a-Klotho coreceptor
effect of FGF-23
increases PO4 excretion in PCT
increases Ca and Na reabsorption in DCT
how does chronic kidney disease effect FGF-23
dysregulation of FGF-23 leads to INCREASED PO4 REABSORPTION –> hyperphosphatemia
how does chronic kidney disease cause mineral bone disease (CKD-MBD)
hyperphosphatemia –> loss in a-Klotho coreceptor –> decreased FGF-23 binding –> overproduction of FGF-23 (lack of negative feedback) –> additional hyperphosphatemia
