Case Study

Question One:

Hypertension (in addition to a number of medical conditions) may be considered as primary or secondary. Explain these concepts giving three examples of secondary hypertension and their pathophysiology.

Most of the conditions that cause secondary hypertension involve the overproduction of one of the body's hormones. Some of the medical problems that can cause secondary hypertension include:

Kidney disease. Secondary hypertension is related to damaged kidneys or to an abnormal narrowing of one or both renal arteries. The renal arteries are the major blood vessels that bring blood to each kidney. When the kidney's blood supply is reduced by a narrowing (called renal artery stenosis), the kidney produces high levels of a hormone called renin. High levels of renin trigger the production of other substances in the body that raise blood pressure, particularly a molecule called angiotensin II.

Adrenal disease. The adrenal glands sit on top of the kidneys and produce several hormones that help regulate blood pressure. Sometimes, one or both adrenal glands make and secrete an excess of one of these hormones.
Three different types of adrenal gland conditions cause high blood pressure:

Pheochromocytoma. A tumour of the adrenal gland that overproduces the hormones epinephrine (adrenalin) and norepinephrine (noradrenalin).
Hyperaldosteronism (also called Conn's syndrome). Both adrenal glands can overproduce the salt-retaining hormone aldosterone or it can arise in a benign adrenal tumour.
Hypercortisolism (also called Cushing's syndrome). Both adrenal glands can overproduce the hormone cortisol or it can arise in a benign or malignant tumour.

Hyperparathyroidism. A hormone called parathormone is made by four tiny glands in the neck called parathyroid glands. If the glands produce too much hormone, calcium levels in the blood increase. People with hyperparathyroidism are more likely to have high blood pressure. The exact reason for this association is not known.

Question Two:

Roger was a symptomatic and only came in for a check up. Why is it important for this 'silent disease' to be detected and appropriately treated?

As blood flows through arteries it pushes against the inside of the artery walls. The more pressure the blood exerts on the artery walls, the higher the blood pressure will be. The size of small arteries also affects the blood pressure. When the muscular walls of arteries are relaxed, or dilated, the pressure of the blood flowing through them is lower than when the artery walls narrow, or constrict.
Blood pressure is highest when the heart beats to push blood out into the arteries. When the heart relaxes to fill with blood again, the pressure is at its lowest point. Blood pressure when the heart beats is called systolic pressure. Blood pressure when the heart is at rest is called diastolic pressure. When blood pressure is measured, the systolic pressure is stated first and the diastolic pressure second. Blood pressure is measured in millimeters of mercury (mm Hg). For example, if a person's systolic pressure is 120 and diastolic pressure is 80, it is written as 120/80 mm Hg. The American Heart Association has long considred blood pressure less than 140 over 90 normal for adults. However, the National Heart, Lung, and Blood Institute in Bethesda, Maryland released new clinical guidelines for blood pressure in 2003, lowering the standard normal readings. A normal reading was lowered to less than 120 over less than 80.

Hypertension is a major health problem, especially because it has no symptoms. Many people have hypertension without knowing it. In the United States, about 50 million people age six and older have high blood pressure. Hypertension is more common in men than women and in people over the age of 65 than in younger persons. More than half of all Americans over the age of 65 have hypertension. It also is more common in African-Americans than in white Americans.
Hypertension is serious because people with the condition have a higher risk for heart disease and other medical problems than people with normal blood pressure. Serious complications can be avoided by getting regular blood pressure checks and treating hypertension as soon as it is diagnosed.

If left untreated, hypertension can lead to the following medical conditions: arteriosclerosis, also called atherosclerosis heart attack stroke enlarged heart kidney damage.

Arteriosclerosis is hardening of the arteries. The walls of arteries have a layer of muscle and elastic tissue that makes them flexible and able to dilate and constrict as blood flows through them. High blood pressure can make the artery walls thicken and harden. When artery walls thicken, the inside of the blood vessel narrows. Cholesterol and fats are more likely to build up on the walls of damaged arteries, making them even narrower. Blood clots also can get trapped in narrowed arteries, blocking the flow of blood.

Arteries narrowed by arteriosclerosis may not deliver enough blood to organs and other tissues. Reduced or blocked blood flow to the heart can cause a heart attack. If an artery to the brain is blocked, a stroke can result.
Hypertension makes the heart work harder to pump blood through the body. The extra workload can make the heart muscle thicken and stretch. When the heart becomes too enlarged it cannot pump enough blood. If the hypertension is not treated, the heart may fail.

The kidneys remove the body's wastes from the blood. If hypertension thickens the arteries to the kidneys, less waste can be filtered from the blood. As the condition worsens, the kidneys fail and wastes build up in the blood. Dialysis or a kidney transplant are needed when the kidneys fail. About 25% of people who receive kidney dialysis have kidney failure caused by hypertension.

Question Three:

The renin-angiotensin system plays a central role in blood pressure regulation. Explain the renin-angiotensin system with reference to Conn's syndrome.

The Renin-Angiotensin-Aldosterone System is a hormone system that regulates BP and fluid balance.

When blood volume is low, the juxtaglomerular cells in the kidneys secrete Renin directly into circulation. Plasma Renin converts a polypeptide called Angiotensinogen, which is secreted from Liver into Angiotensin I, which in turn is converted to Angiotensin II (or ATII) by the enzyme called ACE (Angiotensin converting enzyme) found in the lungs.

It so happens that Angiotensin II is a potent vaso-active peptide that causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin II also stimulates the secretion of the hormone Aldosterone from Adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure.

If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high.

There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control HBP, heart failure, renal failure and the harmful effects of Diabetes.

Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. Angiotensin III has 40% of the pressor action of ATII, but 100% of the aldosterone-producing activity of ATII.

Angiotensin II has autocrine, paracrine and endocrine actions on different systems:

Cardiovascular effects:

AT II is the most powerful vasopressor known, constricting both arteries and veins.
Myocyte growth is stimulated through a local tissue RAAS. The same system can be activated in the smooth muscle cells in conditions of HTN or endothelial damage thus contributing to and accelerating the process of Atherosclerosis.

Neurological effects:

ATII increases the thirst sensation by directly stimulating the Subfornical organ of the brain (Dipsogenic action).
AT II also decreases the response of Baroreceptor reflex.
ATII increases secretions of both ADH and ACTH besides stimulating postganglionic sympathetic fibers to secrete Noradrenaline.
Adrenal effects:

Angiotensin II acts on the Adrenal cortex causing it to release Aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium.

Question Four:

Hypertension is treated using a number of lifestyle and medication approaches. Explain how different anti-hypertensive medications act to reduce blood pressure.

Antihypertensive drugs act by different mechanisms to achieve the same result – to reduce high blood pressure to normal levels. To be able to understand how these drugs act, let us understand how the body usually regulates blood pressure. Blood pressure depends on three important factors – how fast the heart beats, the amount of blood the heart pumps out at each beat and the width of the arteries through which the blood travels.

Each of these factors can be affected by how your nervous system is functioning and the levels of particular hormones in blood. Blood pressure generally increases if

The brain produces excess of catecholamine hormones or
The kidneys produce too much of angiotensin hormone or
There is an excess of sodium in the blood

Each category of antihypertensive drugs acts by regulating one of these processes to control the increase in blood pressure.

Diuretics: Drain out excess sodium and water from your body.
Anti-adrenergics: Act on either the alpha or beta type of receptors and are accordingly called alpha blockers or beta blockers. Alpha blockers block the action of the nervous system on the blood vessels and this prevents the arteries from growing narrow. Beta blockers reduce the heart rate, slow down the strength of each heart contraction and also inhibit production of angiotensin, leading to a drop in blood pressure.

ACE inhibitors: Prevent formation of angiotensin by inhibiting an important enzyme in the kidney.
Calcium channel blockers: Prevent calcium from entering the muscles in the heart and blood vessels; the heart rate drops and blood vessels stay wide open, so the blood pressure does not rise.

Direct renin inhibitors: Prevent the enzyme renin from catalysing the reactions that result in formation of angiotensin; lesser angiotensin production means blood pressure stays low.

Angiotensin receptor blockers: Prevent angiotensin from combining with its receptors and so blood pressure stays normal.