Mechanisms of Diuretic Therapy in Hypertension and Kidney Disease

Jump To Section

• Diuretic Mechanisms in Hypertension
• Physiological Changes Over Time
• Volume Status Assessment
• Chronic Kidney Disease Approach
• Treatment Goals Differences
• Full Transcript

Diuretic Mechanisms in Hypertension

Dr. David Ellison, MD, clarifies a fundamental teaching point for medical professionals. He explains that diuretics in essential hypertension are not primarily used to reduce extracellular fluid volume. Dr. David Ellison, MD, states this is a common misconception among clinicians. The initial physiological response does involve salt and water excretion.

This process leads to a temporary reduction in fluid volume. However, the primary long-term antihypertensive effect stems from a different mechanism.

Physiological Changes Over Time

Dr. David Ellison, MD, describes the fascinating temporal shift in diuretic action. He notes that blood pressure equals cardiac output multiplied by systemic vascular resistance. Initially, diuretic use causes a slight drop in cardiac output and a rise in systemic vascular resistance.

Dr. David Ellison, MD, explains the net effect is still a blood pressure reduction. Over approximately two weeks, the body's fluid volume returns toward normal. Concurrently, systemic vascular resistance falls significantly. After one month, the patient's fluid status is typically normal, but their arterioles are dilated.

Volume Status Assessment

The interview with Dr. Anton Titov, MD, highlights key monitoring parameters. Dr. David Ellison, MD, emphasizes that volume assessment is not critical in essential hypertension treatment. This is because thiazides function as effective vasodilators in this context.

Potassium level monitoring remains crucial due to diuretics' known side effects. Dr. Ellison's explanation provides clarity on why weight and fluid status tracking are less emphasized for hypertensive patients on these medications compared to those with heart failure.

Chronic Kidney Disease Approach

Dr. David Ellison, MD, draws a critical distinction for patients with kidney impairment. He states the approach is "very different" for patients with severe chronic kidney disease, such as stage four. In these cases, extracellular fluid volume overload is a primary concern.

Dr. Ellison recommends a careful physical examination to assess for signs of fluid overload. This includes evaluating for edema, jugular venous distension, and lung crackles. The therapeutic goal shifts fundamentally in this patient population.

Treatment Goals Differences

Dr. David Ellison, MD, summarizes the divergent treatment objectives based on patient diagnosis. In essential hypertension, diuretics lower blood pressure primarily through systemic vasodilation. The mechanism for this vasodilation remains partially understood and is likely multifactorial.

In contrast, for chronic kidney disease patients with hypertension, diuretics work by reducing extracellular fluid volume. Dr. Anton Titov, MD, facilitates this clarification of distinct therapeutic pathways. Both mechanisms effectively reduce blood pressure but through fundamentally different physiological approaches.

Full Transcript

Dr. Anton Titov, MD: The patients with hypertension who chronically use diuretics—is there any criteria apart from the level of the blood pressure? And perhaps the level of potassium is also important? Are there any other tests they can do?

Dr. David Ellison, MD: That's a great question. What I tend to teach to medical students and residents is that most of the time, when we use diuretics in hypertension—in essential hypertension—we're not using them to reduce the extracellular fluid volume. And so, you really don't need to think about whether the patient has signs of congestion, because that's not why we are using the drugs.

So, you give a thiazide diuretic to a patient with hypertension, and you measure their weight, their fluid status, and their systemic vascular resistance. There's a very interesting phenomenon that still is not completely understood. But what happens is initially, the patient will excrete more salt and water; they pee out more salt and water in the urine. And that will reduce their extracellular fluid volume.

And actually, there may be a rise in their systemic vascular resistance. Recall that blood pressure is equal to cardiac output times systemic vascular resistance. And so initially, what happens is the cardiac output will go down a little bit, and the systemic vascular resistance will rise a little bit, but the net effect is a reduction in blood pressure.

But over the course of days—two weeks—that really changes. And the blood volume and the extracellular fluid volume typically return toward normal. It never totally normalizes, but it increases.

During the time that blood volume and the extracellular fluid volume and the weight increase, the systemic vascular resistance falls. So after one month or so on a thiazide diuretic, typically your fluid status in the body is pretty normal. But instead, your arterioles are dilated; you have a reduction in systemic vascular resistance.

Dr. Anton Titov, MD: How the diuretic causes the decline in systemic vascular resistance is still debated.

Dr. David Ellison, MD: I think it's still very confusing. It's probably multifactorial. But this is why when we use thiazide diuretics to treat essential hypertension, we don't think that much about volume, because we are using them to be vasodilators really, and they're very effective as a dilator. So that's why we don't really think about volume in hypertension.

Now, as I mentioned before, that's a very different situation than the patient with chronic kidney disease, especially severe chronic kidney disease. And there's no question that we look for signs of extracellular fluid volume overload.

So, if I have a patient in the clinic who has chronic kidney disease, stage four, and his blood pressure is 190 over 100, I will certainly try and do a careful physical exam and see if they have signs of fluid overload. And many times, those will need an actual reduction in their extracellular fluid volume.

And so, the use of the diuretic in that situation will be for a different purpose. At the end of the day, it still brings down blood pressure, but there it brings down blood pressure by reducing extracellular fluid volume. Whereas in essential hypertension, it brings down blood pressure by causing systemic vasodilation.