Regulation of sodium Flashcards
Why is regulation of sodium important for the body?
Na concentration is the main regulator of ECF fluid (as it is the main regulator of blood osmolalality. THerefore it is also a very important driver of blood volume, and therefore blood pressure
Why is regulation of sodium important for the body?
Na concentration is the main regulator of ECF fluid (as it is the main regulator of blood osmolalality. THerefore it is also a very important driver of blood volume, and therefore blood pressure
Where is Na normally reasborbed?
Under normal conditions, mostly in proximal convuluted tubule and ascending loop of henle
Through which mechanism is Na NORMALLY excreted?
As Na is related to blood pressure, and BP is related to GFR, high Na leads to high BP leading to high GFR->when Na high it is excreted more because of high BP
How are Na levels sensed in the kindey?
The distal conveluted tubule passes very close to the glomerulus, in a zone called the macula densa. The cells there can sense Na levels and will produce renin if it its low
Describe the RAAs system and its consequences in the body.
When Kidney macula densa senses low Na/BP, it produces renin, which is an enzyme that will transform liver Angiotensinogen to Ang I. In lungs, Ang I is converted by ACE to Ang II. Ang II causes vasoconstriction of blood vessels AND increased Adrenal production of Aldosterone. Ald causes increases Na reabsroption in collecting duct, increasing water as well, etc
What other factors control aldosterone? (appart from Ang II)
Low baroreceptor firing and decreased osmolarity (like vasopressin)
On a cellular level, what are the roles of aldosterone? How?
Increase Na uptake, increase K+ excretion, increase H+ secretion
It acts on Type I steroid receptor-dimerises upon binding intracellularly, then goes and acts as TF
Increase production of the Na channels etc
Potentially increases their activity as well
Describe consequences of low aldosterone
Hypoaldosterodism-constant reduced sodium reabsoprtion capacity, increased sodium in urine, lower ECF, lower BP
=> Dizziness, low BP, salt craving, palpitations)
Describes the consequences of high aldosterone
Hyperaldosterodism-reabsorption of Na in distal nephron always high-Reduce urine Na, hypertension, increased ECF, downregulation of RAAs, increased BNP and ANP
=>high BP, muscle weakness, polyuria, thirst
What is Liddle’s syndrome?
mutation of aldosterone activated Na channel-always on. causes same symptoms as hyperaldosteronism
What is the effect of increased/decreased ECF volume and blood pressure on sodium retention
We have baro receptors on the “low pressure” right side of heart and atrium and on “high pressure” side- carotid, aorta, kidney
When the Low pressure OR high pressure side detect lower BP-brainstem signalling to increase SNS and stimulate ADH release. (The kidney sensors also will lead to renin secretion (JGA cells))
when the low pressure ones detect higher than normal BP (atrial stretch), then produce BNP and ANP
What is ANP? (arial natiruetic peptide)
Small peptide made in response to strecth of atrium (high BP)-vasodilates Blood vessels, inhbits sodium retention, inhibits renin and aldosterone => reduces BP
What are ACE inhbitors and what are they used for?
ACE is angiotensin I converting enzyme. ACE inhbitors target the enzyme and reduce its activity, lowering Ang II, reducing vasoconstriction and aldo->lower BP
What diuretics are used to treat blood pressure and why?
Diuretic drugs aim to have more Na released in urine
Osmotic diurectics-like glucose is T2DM-mannitol
Carbonic anhydrase inhbitors
Loop diuretics: Furosemide
Thiazides
K+ sparing diruetics: amilorides, sprionlactone (targets aldo)
why are carbonic anyhydrase inhbitors used to reduce Na?
Carbonic anhydrase activity leads to Na+ re-absorption and increased urinary acidity, as Na can be intaken in exchange for an H+
if no H+, no Na reuptake
How does furosamide work for Na reabsorption?
Blocks the apical channels that intakes 1 Na, 2Cl and 1 H_
How does thiazide work in na reasborption?
Blocks the Na/Cl co import channels
Why is it important to regulate potassium in your body?
Most abundant intracellular ion. High K+ depolarises membranes-causes weird action potentials. arrythmias
Low K+-can produce AP well enough, asystole
How are potassium levels regulated?
As K+ is eaten, it comes to blood where insulin makes it enter cells
In kidneys Potassium is very linked to sodium
Na Intake is nearly always in exchanged for K, and then Na passes to blood with K/Na antiport (2K in, 3 Na out)
Aldosterone, high plasma K, Tubular flow rate, pH will all lead to increase activity of the intake of Na (therefore excretion of K)
To increase K, decrease aldosterone and stuff
what are the causes of hypokaleamia?
Quite common is hospital
Caused by diuretics, vommiting, diarrhoae, genetics (Giterlmans syndrome, mutation in Na/Cl transporer)
What are the main causes of hyperkaleamia?
ACE inhbitors, K+ sparing diuretics, elderly
Recall the normal plasma pH, and the ranged compatible with life. And what about urine?
Plasma pH around 7.4, and ranges can go from 7 to 7.8 about there
Urine on the other hand can go from 4/5 to 9 easy
What is the main pH buffer used in the body? What is its concentration? And where in the kidney is it mostly reabsorbed?
Bicarbonate-HCO3-
Around 24mMol
80% taken up again in proximal conveluted tubule -rest is later
