Pathophysiology of Hypertension

00:00 So, let's talk about the big picture of hypertension. The vast, vast majority of people, 90-95% on the pie chart over there on the right have primary or idiopathic hypertension.

00:15 5-10% of people have some secondary hypertension that's caused by a specific chain or other identifiable cause but that's a distinct minority. Renal artery stenosis is one such etiology. Another one is renin-producing tumors. Obviously that will cause hypertension.

00:35 Another one is hyperaldosteronism. The adrenal cortex cranking out too much aldosterone.

00:41 Pheochromocytomas making too many catecholamines, in particular epinephrine, by a tumor in the adrenal medulla. Polyarteritis nodosa will cause local inflammatory vasoconstriction which can cause hypertension. But the vast majority of the people again have what is called essential hypertension, meaning we don't have a clue. Actually we do have a clue.

01:08 It's really a cumulative effect of several small genetic polymorphisms individually, probably not much of an effect. Cumulatively, they can cause hypertension. There is also interacting environmental factors. How much water are you drinking? How much salt are you eating? Things like that. So, about 5% of patients will have something that's not in the normal range of hypertension. So hypertension, we'll talk about in a minute, is a certain level but 5% of patients overall have something called malignant hypertension.

01:40 If it's untreated can lead to death within 1-2 years. So, much higher mortality than even some of the worst cancers that are out there. So, big picture #2, causes of hypertension.

01:54 So, renal, endocrine, cardiovascular, and neurologic are all mechanisms by which you can get high blood pressure. So let's talk first about the renin angiotensin system. This involves production by the kidney of renin. Okay, so decreased renal perfusion sensed by the juxtaglomerular apparatus cells near the afferent arteriole secreted peptide hormone renin. That renin is produced by the kidney when it senses low flow. That renin will act on angiotensinogen produced by the liver to produce the peptide angiotensin I and then peripheral endothelial cells in the various vascular beds will convert that to angiotensin II which is going to be the major actor as we talked about increasing blood volume and causing vasoconstriction. Renal hypertension, the angiotensin II, there are at least 5 different effects. So just kind of briefly to review them. It acts on the pituitary gland, which will cause antidiuretic hormone secretion which will increase water resorption in the collecting ducts of the kidney. So that's increasing blood volume. Angiotensin II will cause arteriolar vasoconstriction. It causes increased sodium and chloride reabsorption and with it becomes obligate water. So, that's another way to increase volume besides the effects of antidiuretic hormone. You can have increased aldosterone secretion which also acts on the renal tubular epithelial cells to increase sodium and chloride absorption and with it comes water. And then finally, angiotensin II has increased sympathetic activities. So it will act on the neural axis to cause vasoconstriction.

03:53 Very effective. Okay. That's the renal aspect of hypertension. Let's talk about an endocrine aspect of hypertension and mainly this is going to be adrenocortical. So adrenal cortex hyperfunction. Cells making too much of aldosterone, the mineralocorticoid and there are variety of entities from Cushing syndrome primary tumors of the adrenal cortex or those related to increased adrenal corticotropic hormone, ACTH, secretion by the pituitary. You can have primary hyperaldosteronism so you just make too much aldosterone just because you have an enzymatic defect. Congenital adrenal hyperplasia due to small genetic polymorphisms and even licorice ingestion. So it's an interesting cause of hypertension and we're not going to get into the pathophysiology here. You can have exogenous hormones. So glucocorticoids, estrogen, sympathomimetics. So things that are going to increase the cholinergic signaling. Tyramine-containing foods, all those are exogenous causes of having increased aldosterone production. Acromegaly which is a primary growth hormone producing tumor of the pituitary, which will cause systemic manifestations and endocrine hypertension. Hypothyroidism which will also cause increased volume retention and that's why it causes endocrine hypertension. And then finally, hyperthyroidism which causes thyrotoxicosis. Pregnancy thru the effects of estrogen can also cause a transient hypertension and also due to effects on the placental vasculature. Cardiovascular causes of hypertension include coarctation of aorta so a genetic defect that causes constriction of the proximal aorta. Polyarteritis nodosa, inflammation of the vessels, will cause increase vascular tone particularly in the arterioles.

06:02 And increased intravascular volume can be a cause of cardiovascular hypertension.

06:07 Increased cardiac output, heart squeezing more aggressively or at a higher rate. And notably for the geriatric population rigidity of the aorta. As we age, the aorta accumulates more and more fibrous connective tissue and tends to lose the elasticity that had characterized the earlier younger version of itself. As a result, the pipe gets stiffer and stiffer and stiffer. So instead of dilating during systole, it's now kind of a stiff pipe that leads to a cardiovascular reason to have high blood pressure particularly in the older population. And then things having to do with neurologic causes, psychogenic. So I can get very agitated. As you get readyfor exam, you can get agitated that will raise your blood pressure. You can get it from increased intracranial pressure due to the release of cathecols. You can get it from sleep apnea probably due to relatively high levels of hypoxia. And then acute stress including surgery can be a means by which you can get neurologic hypertension. Essential hypertension can be in part because there's just decreased or diminished sodium excretion and clearly that's going to affect blood volume.

07:20 The more sodium that you retain, the more water you retain with it and the greater the blood volume. That will increase cardiac output but that will also elevate blood pressure.

07:32 Increased vascular resistance can be due to structural changes in the vessel wall or increased tone, vasoconstriction. A variety of genetic factors can lead to essential hypertension. The boards like to quiz you on these. These are very very rare causes for hypertension, but they do in fact occur and these are due to genetic variations in the aldosterone synthase genes so you would get increased overall aldosterone secretion and salt and water retention or mutations that affect sodium resorption within the renal tubules. If you have increased levels of sodium resorption, you will have increased levels of water resorption as well and diseases such as Little's syndrome will be a cause for hypertension. And then finally, a variety of environmental factors. Remember that hypertension for most of us, essential hypertension, primary hypertension is going to be a combination of little tiny genetic polymorphisms interacting with the environment.

08:46 And environment includes stress, obesity, smoking, physical inactivity, high salt intake, all of those will act in association with the various other genetic factors.