what senses it: baroreceptors in arteries, veins and the juxtaglomerular apparatus
what they do: the JGA senses not enough sodium in ascending limb of loop of Henle, releases renin, the sympathetic nervous system shrinks vessels to keep BP up, and in severe cases (hemorrhage) the aortic and pulmonary baroreceptors stimulate ADH release via hypothalamic hormones
ADH increases water reabsorbtion by collecting duct, increasing fluid retention.
Renin from the JGA causes conversion of Angiotensin I to the active form, angiotensin II.
Angiotensin II is a powerful vasoconstrictor. It stimulates Aldosterone release, constricts afferent and efferent arterioles, increases oncotic pressure (protein concentration) in peritubular capillaries and decreases hydrostatic pressure, lowers GFR, thus increasing sodium and water reabsorption in proximal tubule, increasing fluid retention.
Aldosterone increases Na+ reabsorbtion in distal tubule & collecting duct, increasing fluid retention. Drugs that suppress this hormone function as diuretics that are unique in that they do not increase potassium excretion.
RAAS = A system of hormones (renin, angiotensin II and aldosterone) that work together to increase fluid retention and blood pressure, and reinforce each other.
Sympathetic nervous activity (autonomic nervous system) in response to hypovolemia constricts afferent and efferent arterioles in glomerulus, lowering GFR and increasing fluid retention.
CONGESTIVE HEART FAILURE and renovascular hypertension (due to renal artery stenosis) both lower renal blood flow (RBF). CHF lowers it because the heart is overloaded and weakened, can't pump hard as it should. Renal artery stenosis lowers it because the blood can't get through. Both are wrongly interpreted by the kidney as systemic hypovolemia (when in fact it is local), and stimulate the RAAS system causing more fluid retention and exacerbating the problem. This is why diuretics are desperately needed in the case of CHF.
HYPERVOLEMIA first triggers pressure natriuresis which increases GFR and lowers reabsorbtion of water & sodium in proximal tubule, causes suppression of RAAS system, lowering reabsorption in proximal and distal tubules, and causes release of ANP, (atrial natriuretic peptide) which increases GFR by lowering reabsorption of sodium and water at the collecting duct.
HIGH BLOOD PRESSURE
risk factors: genetics, age, obesity, insulin resistance
BP = CO x TPR
blood pressure = cardiac output x total peripheral resistance
Primary hypertension comprises 90% of high blood pressure cases and is due to increases in BOTH CO and TPR. CO is increased by high catecholamines, increased sympathetic nervous activity (possibly due to stress), high sodium consumption and retention, and increased RAAS. TPR is increased by the destruction of some peripheral blood vessels, systemic vasoconstriction due to excessive RAAS, sympathetic nervous activity, decreased endothelial mediated vasodilation (downregulated nitrous oxide), and long term by hypertrophy and scarring of the stressed vessel walls, reducing compliance. All these factors conspire to push the pressure natriuresis threshold to the right, permanently increasing the systemic BP. NO is activated in the vasa recta to dilate those vessels and reduce the risk of anoxia in kidney tissue.
Both sodium and angiotensin II produce ROS (reactive oxygen species = free radicals that do oxidative damage to blood vessels) which damage the vasa recta. The damaged vasa recta vasoconstricts even more due to increased RAAS which inhibits vasodilation due to NO, prostaglandins or dopamine.
Hypertension develops in 3 phases:
I: persistent excess angiotensin II and sympathetic nervous activity
II: chronic vasoconstriction due to imbalanced AII and nitrous oxide (NO), oxidative stress and damage to renal capillaries resulting in reduced lumen size and smooth muscle hypertrophy, sodium retention due to kidney damage which further increases fluid retention and BP
III: but fluid retention isn't characteristic of high BP because pressure natriuresis curve shifts right and increased pressure helps kidneys ("hypertensive kidney") excrete enough fluids to maintain a "normal" amount of fluid in body
Most potassium is intracellular, and the levels are closely controlled in the body. Too little causes muscle weakness, twitches and tetany, and can be caused by diarrhea or some diuretics. Too much is almost always caused by ingesting it, and causes heart arrhythmias and nervous excitability. Most potassium (67%) is reabsorbed in the proximal tubules (20% in thick ascending limbs), but the reabsorption by the alpha intercalated cells in the DISTAL TUBULE and COLLECTING DUCT is not hormonally regulated. Excretion IS hormonally regulated, because the sodium potassium pump (aka Na/K ATPase) in the principal cells of the COLLECTING TUBULE is upregulated by ALDOSTERONE. More pumps means more K out and more Na in.
OSMOTIC DIURETICS such as glucose, sucrose, mannitol, corn silk and althea work at the PCT to increase excretion of water by pulling it with them osmotically when they are excreted. Normally glucose is not excreted in the urine, but diabetics with very high blood sugar overwhelm the kidneys' ability to reabsorb sugar and so may become dehydrated this way. Most of these increase potassium secretion too.
Carbonic anhydrase inhibitors are used to regulate acid/base and water/bicarbonate excretion.
THIAZIDE DIURETICS are commonly paired with an ACE inhibitor to treat hypertension. The ACE inhibitor stops the production of Angiotensin I so there is less Angiotensin II. The thiazides (bendrofluazide, chlorthalidone) inhibit Na-Cl reabsorption from the distal tubules causing osmotic retention of fluid in the DISTAL excretory tubules. Any hypovolemia triggers aldosteron release and potassium secretion, and with thiazides there is a risk of hypokalemia.
LOOP DIURETICS (furosemide = lasix, ethacrynic acid, bumetanide) act on the THICK ASCENDING LIMB by inhibiting sodium, potassium and cloride reabsorption, and that keeps the water in the ducts. CAFFEINE acts on both proximal and distal tubules by preventing sodium reabsorption. All decrease the hyperosmolarity of the medulla of the kidney.
ALDOSTERONE INHIBITORS are also known as POTASSIUM SPARING DIURETICS (spironolactone, amiloride) and increase excretion of sodium and water while retaining potassium in the COLLECTING TUBULES. These are less commonly used because they can cause substantial fluid retention fluctuations.