Lecture 22 - Sodium Balance

why is sodium so important?

it is critical for life, the total volume has major impact on total blood volume, impacts blood pressure, it is required for normal blood volume, blood pressure and organ perfusion, used to be very scarce so we were designed to retain it in order to maintain blood volume, now we have too much of it causing increasing cases of high blood pressure and associated diseases

in what ways do we lose sodium?

by excessive sweating, diarrhea, vomiting, osmotic diuresis, diuretics, blood loss and decreased intake

osmotic diuresis

common ways diabetes impacts the patient, causes a lack of control on glucose so you cant reabsorb it which increases flow rates causing you to lose sodium

how do you gain sodium?

mainly diet through processed and fast foods

bowman’s capsule

where capillary produces glomerular ultrafiltrate based on starling forces so it wanders into the tubule

proximal tubule reabsorption

70%

loop of Henle reabsorption

20-30%

distal tubule reabsorption

5-10%

collecting duct reabsorption

1-3%, fine tuning of Na+ absorption happens here

co-transporter actions along the Na+ concentration gradient

reabsorption starts off high and gradually decreases along the nephron and the co-transported use low intracellular Na+ and Na+//K+ ATPase on basolateral membrane maintains lower intracellular Na+ concentration leading to the reclamation of it alongside water

NCCK transporter

co-transported in the descending limb

Na+/Cl- transporter

co-transporter in the distal convoluted tubule

normal filtered volume

150 L

normal Na+ concentration and filtration

140 mMol/L and filtered 21,000 mmols where less than 1% is filtered through the kidneys and that same amount is excreted to ensure sodium balance

what happens to Na+ filtration when there is a sodium deficit

in this case less than .005% of total Na+ would be filtered and excreted which is about 10 mmoles, this is done by increasing the reabsorption of Na+ to excrete less of it helping water retention in hot climates like the desert where there is less water available stopping/managing dehydration

plasma volume role in Na+ balance

it is what allows us to gage the Na+ volume in the body

arterial baroreceptors location

located in the carotid body and aortic arch, respond depending on how full they are, like a balloon where the more plasma there is the bigger it gets

afferent arterioles location

located in the kidneys

atrial stretch receptors location

located in the heart

carotid sinus receptors

gages the amount of fluid in arterial receptors that are delivering blood to the brain

aortic arch receptors

baroreceptor communication through vagus nerve and IX nerve

brainstem activity

receives input from the carotic sinus nerve, nerve IX and vagus nerve X, the higher the amount of brain traffic sent afferently the higher the volume and pressure

wall tension

a function of volume and pressure, an increase in the two results in an increase in the plasma flow in the aortic arch

cardio regulatory center and chemoreceptors in medulla oblongata

receives traffic via vagus nerve and IX cranial nerve

baroreceptors and carotid body receptors

provides negative influence so the more nerve traffic that gets into the brainstem the more downregulation of activity within the cardio regulatory center which in turn means lower SNS nerve output and naturally if volume/pressure is low this decreases nerve traffic which increases SNS nerve output

negative influence

increase in nerve traffic = increase in downregulation of activity within cardiovascular center = decrease in SNS nerve output

positive influence

decrease in volume/pressure = decrease in nerve traffic = increase in SNS nerve output

SNS activation and the renin angiotensin system

renin is a poilytic enzyme present in mainly the afferent arteriole and the juxtaglomerulus apparatus, it converts angiotensin into angiotensin 1 through SNS activity, this then gets cleaved to angiotensin 2 with a chymase and this would be the active form acting on the kidney

angiotensin 2

increases na+ and water reabsorption returning it us to a setpoint to maintain sodium balance

the afferent arteriole and influence on the renin angiotensin system

a decrease in pressure/flow in the afferent arteriole will trigger the release of renin activating angiotensin II to mediate sodium balance

regulation of renin secretion

if arterial blood pressure sensed by afferent arteriolar stretch in the macula densa will cause an increase in renin activity, if the SNS is active this will also increase release of renin and finally dietary sodium/low intake will increase sodium, the angiotensin activity is mediated by baroreceptors in the arch of the aorta and the carotid body in the SNS, and the afferent arteriole

angiotensin in the proximal tubule

it drives the activity of the NHE3 luminal sodium transport protein and norepinephrine via SNS activity, ultimately increasing Na+ movement into the cells so it goes into the basolateral membrane so it can get reabsorbed

angiotensin in the distal convoluted tubule

doesn’t directly activate NCC but protein and kinases are involve too, it increases Na+/Cl- movement into the cell, the setpoint moves so less Na+ leaves the distal convoluted tubule

hemodynamic effects of angiotension

these effects act in the renal microcirculation that enhance proximal tubule reabsorption causing constriction of efferent arteriole, this increase in resistance lowers pressure in the post-glomerular capillary which increases concentration

reabsorption in peritubular capillaries

lower hydrostatic pressure in peritubular capillaries results in net reabsorption of interstitial fluid, the angiotensin II increases resistance in the efferent arteriole which then lowers it in the post-glomerular capillary increasing concentration, this lowers pressure in the capillaries with increases osmotic pressure favoring water movement into peritubular capillary so decreasing hydrostatic pressure increases oncotic putting water in the lumen and na+ drags in with it

angiotensin II effects on the reabsorption in the peritubular capillaries

it increases filtration fraction and increase the oncotic pressure in the capillaries

angiotensin impact on aldosterone

angiotensin II synthesizes it and releases it, this is a hormone located in the adrenal cortex and produced by the glomerulosa cells in the cortex of the adrenal gland

aldosterone receptors

located in the collecting duct, increasing number and open probability of sodium channels to increase sodium reabsorption cause more epithelial channels in the membrane that are open favors the movement of Na+ into tubular cells for reabsorption

how does aldosterone act on principal cells?

it combines with a cytoplasmic receptor, the hormone receptor complex initiates transcription in the nucleus, the translation and protein synthesis makes new protein channels and pumps, aldosterone induced proteins modulate existing channels and pumps, results in increased Na+

how does angiotensin II act on the nephron?

at the proximal convoluted tubule it changes starling forces that favor reabsorption of salt and water, in the distal convoluted tubule it drives it to reabsorb more Na+ via Na+/Cl- co-transporter and finally at the collecting duct it is released so that Na+ opens channels

what happens to sodium levels when you eat too much sodium or sit in a hot tub for too long?

the water pressure transmits pressure to the interstitial space, this changes starling forces driving water into the vascular compartment shifting na+ there so baroreceptors can suddenly increase volume and pressure

how do we shut down the renin angiotensin system

by increasing baroreceptor activity and decreasing SNS activity but we also take advantage of another volume receptor where kidney try to put out more Na+ to return to balance in response to decreased Na+ reabsorption through less na+/k+ exchange activity which decreases co-transport lowering aldosterone and the amount of open Na+ channels

cardiac atria

acts as a volume receptor the atrial myocytes secrete a hormone in response to atrial stretch signaling the kidney to reduce na+ secretion, this explains increased need to pee when you go swimming, increase vascular volume will increase stretch of atrial myocytes which increases ANP causing vasodilation, this in turn increases GFR and reduces sodium reabsorption in the collecting duct

ANP (atrial diuretic peptide)

it opposes effects of aldosterone reducing the reabsorption of sodium via vasodilation, responds to low pressure/volume

how accurately does the kidney maintain ECF volume?

if you take people on a constant sodium intake then suddenly increase dietary sodium , when intake increases, excretion does not increase immediately so ECF volume increases (happens over a few days), increase in Na+ reabsorption = increase in Na+ content until levels are the same, after a few days intake will equal excretion meaning a new steady state at expanded ECF volume

case of the day

denise is 16 yr old girl brought into a clinic in haiti, 12hrs ago she started having fever, abdominal cramps, and profuse water diarrhea as much as 1 L/h, her BP is 90/50 and HR is 130 bpm, she is lethargic, unable to drink, sunken eyes and poor skin turgor

case of the day diagnosis

cholera, she has severe depletion of sodium due to high stool losses via diarrhea, very low ECF volume, needs immediate intravenous sodium and water replacement, isotonic saline is need at more than 10% her body weight

oral rehydration fluid

NaCl, glucose, potassium chloride and sodium citrate, if she could drink give her soup cause highest sodium content