1) Explain how urine osmolarity is hormonally regulated

2) Describe the regulation of major ions by the kidney.

3) Please include references if available

 

1. Explain how urine osmolarity is hormonally regulated

(Please see attached file for the summarized table of hormones affecting urine osmolarity)

ALDOSTERONE

• secreted by zona glomerulosa of adrenal cortex
• Primary site of action: Principal cells of cortical collecting tubules
• Mechanism: stimulates Na+-K+ ATPase to increase Na+ reabsorption and K+ secretion. It also increases Na+ permeability of luminal side. Its stimulation of NaCl reabsorption in the distal tubule and collecting duct indirectly increases water reabsorption by this nephron segment

ANGIOTENSIN II

• Most powerful sodium retaining hormone
• Increase Na+ and water reabsorption by: stimulating aldosterone secretion; constricting efferent arterioles; directly stimulating Na reabsorption in Proximal tubule, loop of henle, distal tubule, and collecting tubule

Antidiuretic Hormone (ADH)

• most important hormone that regulates reabsorption of water in the kidneys
• Stimulus for release - increase in plasma osmolality and decrease in blood volume
• It increases water permeability of Distal tubule, collecting tubule, and collecting duct
• It stimulates insertion of water channels and aquaporins into the membrane tubules
• It binds with V2 receptors in the lat DT, CT, CD increasing cAMP -> activating protein kinases -> results in insertion of vesicles containing Aquaporin 2 (AQP2) water channels into the apical memebrane of the cells

Atrial natriuretic peptide (ANP) and Brain natriuretic peptide (BNP)

• ANP is a protein polypeptide hormone secreted by atrial myocytes and BNP from cardial ventricles that is produced during volume distention -> inhibits sodium and water reabsorption by renal tubules (collecting ducts) -> increases urinary secretion of Na+ and water -> return of blood volume to normal
• Has the opposite effect of aldosterone -> it generates sodium loss
• It increases GFR by causing vasodilation of the afferent glomerular arterioles
• Decreases sodium reabsorption in the DCT and cortical collecting duct via guanosine 3' 5' - cyclic monophosphate dependent phosphorylation of epithelial sodium channel
• Inhibits renin secretion

Sympathetic nervous system (epinephrine and norepinephrine)

• Decreases Na+ and water excretion by constricting renal arterioles -> decreases GFR
• Increase Na+ and water reabsoprtion in PT, TALH, distal tubules
• Increases renin release and angiotensin II -> increase tubular reabsorption and decrease renal Na+ excretion

Urodilatin

• Secreted by Distal tubule and collecting duct
• Not present in systemic circulation
• More potent in natriuretic and diuretic properties than ANP
• Stimulated by the rise of blood pressure and increase in effective circulating volume
• Inhibits NaCl and water reabsorption of collecting duct

Dopamine

• A catelcholamine released from dopaminergic nerves in kidneys
• Act opposite norepinephrine and epinephrine
• Stimulated by increase effective circulating volume
• Directly inhibits NaCl and water reabsoprtion in PT

Uroguanylin

• Produced by neuroendocrine cells in the intestines in response to oral ingestion of NaCl
• Inhibits NaCl and water reabsorption by the kidneys
• Natriuretic response of kidneys to NaCl are more pronounced when given orally because of the secretion of this hormone

2. Describe the regulation of major ions by the kidney.

A. Glomerulo-Tubular Balance

• Ability of tubules to increase Na+ and water reabsorption in response to increased filtered Na+ load
• A constant fraction of filtered Na+ and water is reabsorbed from proximal tubule despite variations of GFR
• Helps prevent overloading of distal tubule when GFR increases

B. Peritubular capillaries and renal interstitial fluid physical forces - Starling forces

• Starling forces regulate NaCl and water reabsorption across proximal tubule into the capillaries
• Starling forces favoring movement of solutes and water to capillaries: 1. capillary oncotic pressure; 2. interstitial space hydrostatic pressure
• Opposing forces: interstitial oncotic pressure and capillary hydrostatic pressure
• Starling forces do not affect transport of loop of Henle, distal tubule, and collecting duct because these segments are less permeable to water than proximal tubule

3. Please include references if available

• Rodwell et al, 2015. Harper's Biochemistry 30th ed
• Lieberman et al, 2015. Mark's Essential of Biochemistry 2nd ed
• Kasper et al, 2018, Harrison's Principle of Internal Medicine, 20th ed
• Guyton, A., MD. and Hall, J.E., PhD. Textbook of Medical Physiology, 13th ed, 2015
• Berne, R., Levy, M., Koeppen, B., Stanton, B. Physiology, Update version 7th edition, 2017
• Widmaier, R., Raff, H., Strang, K., Vander's Human Physiology 15th edition 2019
• Boron, W., Boulpaep, E. Medical Physiology, 3rd edition, 2016

Please see the attached file for the complete solution