Hormones and the Kidney - Slotki Flashcards
Hormones released by the kidney
Hormones acting on the kidney
Out:
Renin
Calcitriol
Erythropoietin
Prostaglandins-acts through adenylyl cyclase-cAMP
Angiotensin II-acts through phosphatidyl inositol pathway and adenylyl cyclase-cAMP
Dopamine
Kinins
Endothelin
NO
In:
Vasopressin
PTH
b-adrenergic
-Norepinephrine-acts through phosphatidyl inositol pathway and DAG
-act on cAMP through adenylyl cyclase
Aldosterone
Nitriuretic peptides- ANP from arteries, urodilatin, BNP, endogenous digitalis-like hormone, guanylins (made in gut)
Insulin
IGF-1
FGF-23
Actions of vasopressin
Stimuli and inhibitors
Water reabsorption
-CCT (principal cells) and MCT
Urea reabsorption
-MCT
Electrolyte handling
Vascular resistance
Prostaglandin production (modulation)
Regulation of cortisol release
Release of factor VIII and vW factor
Stimuli:
Stimuli
Hyperosmolarity
Hypovolemia
Stress, eg pain
Nausea
Pregnancy
Hypoglycemia
Nicotine
Morphine
Other drugs
Inhibitors:
Inhibitors
Hypoosmolarity
Hypervolemia
Ethanol
Phenytoin
Erythropoietin:
Properties
Where are receptors?
Mechanism
Regulation
Role in ESRD
34 kDa glycoprotein
From fibroblast-like renal interstitial cell
Receptors in many tissues
Receptors in: mone marrow (CFU-E), Uterus, smooth muscle, vascular endothelial cell, mesangial cell and tubular cell
Signal transduction via JAK-STAT & Ras/MAP kinase pathways
Controls RBC production by promoting survival, proliferation, and differentiation of erythroid progenitor cells
Cytokine/growth factor
Regulation: Hypoxia –> HIF stabilization –> erythropoietin gene stimulation –> EPO release –> erythropoiesis
If normal O2: HIF-2alpha is hydroxylated by PHD1-3 to form complex with pVHL to signal proteasome degradation of HIF
in ESRD:
Benefits:
Correction of anemia
Improved well-being
Improved LV function
Improved cognitive function
?Stabilization of kidney function in CKD
Problems (more if less responsive to EPO and given higher dose):
Hypertension
Fistula clotting (more viscious blood)
Functional iron deficiency (tx: IV iron)
Increased stroke risk if Hb>13
ANP:
Actions
When is it secreted?
Direct vasodilation
Increased urinary Na+ and water excretion
Increases GFR by Afferent arterial dilation and Efferent arterial constriction
Decreased Na+ reabsorption in papillary collecting duct and maybe in proximal tubule (leading to peritubular capillary pressure and icnreased local dopamine release)
Decreased Renin release
Decreased AngII and K+ induced aldosterone secretion
Decreased AngII induced Na+ reabsorption and aldosterone release
Decreased Collecting tubular reponse to ADH
Secreted in response to:
Volume overload, CHF, CRF and cirrhosis, atrial stretch. Not a diuretic because stimulates RAAS.
Catecholamine effect on the kidney
Beta 1 stimulates RAAS which leads to increased Proximal and loop Na transport (together with alpha 1) which leads to Na reabsorption. Modulated by alpha 2 which inhibits proximal and loop Na transport
Decreased ECF volume (from volume depletion or hypotension) increases SNS activity which increases catecholamines which decrease RBF through renal vasoconstriction which decreases peritubular bloodflow which supports proximal and loop Na transport.
Dopamine and the kidney
Most used vasoconstrictive hormone for hypotension.
Low concentration: Increased RBF fo afferent AND efferent so no effect on GFR.
In high doses acts like epinepherine with alpha 1 to decrease RBF.
Decrease Na reabsorption
In proximal tubule: Direct effect on BM Na/K ATP-ase and Na/H antiporter as a diuretic.
In CCT: Direct action on Na/K ATPase and also secondary inhibition through PGE2
Kinins and the kidney
Kininogen activated by Kallikrein enzyme which is released from the distal convoluted tubule and CNT (connecting tubule). Kininogen leads to bradykinin (in papillary collecting duct) which reduces Na reabsorption in medullary collecting duct. ACE inhibitors inhibit breakdown of bradykinin (by kininases) which leads to coughing.
Endothelin, NO and the kidney
Endothelin is the most powerful vasoconstricter in the body. It acts through the endothelium directly to vasoconstrict the kidney, decrease renal flow and GFR and through increased PGE2 to decrease Na/K ATPase to cause netriuresis.
NO is a complementary syngergist and antagonist by also causing natriuresis in the IMCD and by causing renal vasodilation in the endothelium to increase renal blood flow.
Insulin and GH and the kidney
Hyperinsulinemia (from insulin resistance or metabolic syndrome) causes increased SNS activity and NA reabsorption which both cause hypertension.
GH causes increased IGF1 which causes increased phosphate reabsorption in the proximal tubule, gluconeogenesis and increased RBF and GFR
