Endocrinology: The Endocrine Control of Salt and Water Balance

ECFV (Extracellular Fluid Volume) = interstitial water + plasma (1/3 of the body)

Control includes the absorptive and excretory processes in the GI (waste), kidneys (urine), skin (sweat) and lungs (water vapor)

*Remember that glucose and Na+ share concentration characteristics via a symport channel.
-Water comes in through aquaporins (water channels)


Kidneys:

Na+ ions move down concentration gradients by co-transporting with glucose, while water moves passively via aquaporins. 

JG cells (which contained renin-filled granules) sit close to glomerulus of renal nephron

     -Macula densa cells detect the Na+ ion change 

Decreased Na+ ion concentration (detected by macula densa cells and communicated to the JG cells) ----> renin secreted into blood

JG cells secrete renin --> renin converts angiotensinogen into AI --> conversion to AII stimulates the adrenal cortical glomerulosa cells to produce aldosterone 

Barely a sixth of the glomerular filtrate entering the nephron actually reaches the bladder. 

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The skin and lungs are innervated by cholinergic (ACh) SN neurons. The eccrine glands produce the sweat that promotes the cooling of the body once the body temperature rises: 

     -Meanwhile the apocrine glands are more to do arm pit sweat and pheromone secretion. 

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Both AII and aldosterone receptors are present along the GI tract so: 

     -All stimulates contraction of GI via angiotensin type I receptors (ATR1), present in smooth muscle (esophagus, jejunum) 

     -Angiotensin type II receptors (ATR2) are present in epithelial cells and may stimulate HCO3 and K+ secretion 

MRs are mainly found in the colon, and aldosterone stimulates Na+ absorption and K+ secretion particularly along the colon. 

*Since progesterone inhibits Na+ reabsorption in the renal distal nephron it is thought likely that it would also have the same effects in the GI tract. 

T3 and T4 stimulate Na+ reabsorption, which is thought to be why individuals with hypothyroidism often crave salt. 

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Natriuretic peptides are involved in loss of Na+ in urine 

Peptides that cause naturesis and counteract vasoconsstriction and Na+ retaining effects of the RAAS.

     -ANP - released by atrial myocytes when stretched by increase in venous return 

     -BNP - produced by the ventricles of the heart, and some by the neurons in the brain 

     -CNP - produced in the brain and endothelial cells 

ANP and BNP are both produced from pro-hormones and then inactivated by endopeptidase 

Natriuretic peptide receptors: NPRA and NPRB (Transmembrane via guanyl cyclase and cGMP)

     -ANP and BNP bind NPRA; CNP binds NPRB

Effects of the natriuretic peptides (NPs):

• Dilate vasculature, decreasing venous and arterial pressures
• Stimulate production of calcitonin gene-related peptide which also dilates vessels 
• Increase GFR by dilating afferent arterioles --> increasing Na+ load in fluid entering proximal convoluted tubules. 
• Decrease proximal convoluted tubule and cortical collecting duct (which VP acts on) Na+ reabsorption causing natriuresis (expelling out of Na+ ions through the urine) 

Calcitonin tones down Ca2+ in the plasma. It also inhibits Na+ reabsorption in ascending limb of Loop of Henle

Androgens and hypertension

• Associated with decreased levels of NP 
• Androgens tend to increase Na+ retention, and decrease Na+ excretion

So the reason why men are more prone to hypertension is because androgens increase angiotensinogen which increases AII and aldosterone production 

Testosterone can also up-regulate the mineralosensitive apical Na+ channel

• Increased renal Na+ reabsorption in distal nephron
• Causes an indirect effect via the RAAS 
• Increased water reabsorption 

Estrogens do the opposite: 

• Increase angiotensinogen BUT they inhibit ACE levels and AII production 
• Reduce AII synthesis and activity in vascular tissue by decreasing ATR1
• Stimulate release of ANP and BNP (which has receptor NPRA) 

Progesterone can bind to MR and are able to have some aldosterone effects but they tend to, in the long term, increase natriuresis, and also appear to increase ANP effects. 

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Catecholamines:

• Increase Na+ reabsorption 
• Sympathetic stimulation of the JG cells leads to increased renin secretion and RAAS
• Increased vasoconstriction of efferent arterioles occurs since catecholamines increase GFR
• Consequence: Increased stimulation of proximal tubular Na+ reabsorption 

Iodothyronines (T3, T4)

• Stimulate proximal tubular Na+ (and water) reabsorption

Vasopressin (or ADH)

• Acts via the V2 receptor, and can stimulate NaCl reabsorption in the ascending loop of Henle and collecting duct. 
• Does this by stimulating and then inserting new Na+ channels into the apical membrane. 

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Renal Water absorption is directly influenced by Na+ reabsorption in proximal and distal tubules. 

• AII and aldosterone raise plasma Na+ and stimulates osmoreceptors outside BBB, which stimulates the hypothalamic thirst center. 

*Oxytocin may play a small role here via V2 but affinity is very low. 

Hyponatremia:

-Can be caused by pathologies like Addison's disease and SIADH (syndrome of inappropriate VP hypersecretion) 

Hypernatremia:

-Can be caused by pathologies like Conn's syndrome (hyperaldosteronism) or Cushing's syndrome (hypercortisolism)

-Sometimes hypernatremia can be mainly caused by a lack of ADH-directed diuresis (increased production of urine) 

• Reduced water reabsorption in collecting ducts 
• Plasma Na+ increases 
• Results in Diabetes Insipidus  

Development of hypertension and hormonal influences

Compensatory mechanisms: 

Reflex decrease in sympathetic activity due to expansion of the ECFV: 

• Results in ANP and BNP (which have the receptor NPRA) promoting natriuresis and diuresis
• Increase in arterial pressure --> decrease in renal SN activity --> increased GFR and decreased RAAS activity --> further diuresis and natriuresis --> restoring of arterial BP back to normal.