Possible Causes of Hypertension in Young People

1. What are the possible causes of hypertension in young people?

2. How and where are catecholamines synthesized?

3. How do catecholamines control blood pressure and heart rate?

4. Why was it necessary for the G.P. measure urine catecholamines?

5. What does a high urinary metanephrine concentration indicate?

This assignment is based on the case study of Miss Chan, who is a 26 years old woman, having chest pain, sweating, extreme anxiety and abdominal pain with an increased heart rate. She was having these issues over the past few months and observed that, these issues arise after any kind of hard work. Miss Chan also has a family history of death due to heart disease. Therefore, her case needs significant care and consideration. Her reports also show high blood pressure and high pulse rate.

1. In middle age, elevated blood pressure has been found to affect the lifestyle of young adults, especially at the age of twenty five, which enhances the risk of clogged heart arteries by the middle age, found by a U. S. study. It was also found by Acton (2012) that, in young adulthood, hypertension is connected with the high risk of calcium build up in heart arteries at the age of twenty five, which enhances the risk of blood clogging. The reason behind hypertension and calcium build up can be said to be the result of lifestyle changes. At this age, diet changes, hormonal changes and lack of exercise are the important causes of hypertension in young people. There are a number of other health issues, which enhances the risk of hypertension in young adults (Damanhuri, 2012). These include drugs, lifestyle, consumption of unhealthy street food, changes in life style and nutritional diet, hyperthyroidism and aldosteronism. The secondary causes of hypertension include ‘ABCDE’, obstructive sleep apnea; Bruits; catecholamines, coartation and cushing’s syndrome; drugs and diet as well as endocrine and erythropoietin disorders.

In case of Miss Chan, her physical examination showed elevated blood pressure of 110/180 and excessive sweating. The cause of her symptoms could be due to elevated catecholamine levels, which play an important role in establishing white-coat hypertension and OSA. She was also diagnosed to have abdomen pain, which indicate the presence of abdominal bruits. The result of plasma also indicates the role of catecholamines in the elevated level of blood pressure (Eiden, 2013). The urine report of Miss Chan indicated elevated levels of metanephrine,  adrenaline, noradrenaline in blood plasma, indicating elevated levels of hypertension.

2. Catecholamines are the monoamines, which are organic compounds having a catechol group along with an amine in the chain. These are derivatives of biological amino acids and have significant function in the regulatory pathways. The catecholamines have been derived from atyrosine amino acids. These are bound to plasma proteins in circulation and are water soluble (Eleftheriou and Scott 2012). The catecholamine groups include epinephrine or adrenaline, norepinephrine or noradrenaline and dopamine produced from tyrosine and phenylalanine. These epinephrines and norepinephrines are secreted from the adrenal medulla of adrenal glands. These are called stress hormones, which are secreted in response to any stress situation. As in the case of Miss Chan, when she rushes from garden towards her room to receive a phone call, such hormones are secreted as a response of sudden stress and disturbance in the body’s homeostasis. This class of hormones has a distinct structure, a benzene ring with two hydroxyl groups, along with an intermediate ethyl chain and a terminal amine group.

Synthesis and Function of Catecholamines

The catecholamines are produced by the chroimaffin cells in the adrenal medulla and the postganglionic fibers in the human nervous system (Goldstein 2013). On the other hand, being a neurotransmitter dopamine is widely produced in the neuronal cell bodies within two areas of brainstem, the ventral tegmental area and the substantia nigra.

Within these catecholamines, from DOPA, dopamine is first synthesized.. The epinephrine and norepinephrines are then produced after metabolic modification of dopamine. Tyrosine hydroxylase oxidizes tyrosine thereby form DOPA or Dihydroxyphenylalanine (Ice and James 2012). Then DOPA decarboxylase releases carbon dioxide from DOPA and the resultant substance is Dopamine. Then Dopamine hydroxylase modifies dopamine to produce norepinephrine. From the final product, epinephrine is being produced by methylation, where SAM acts as a methyl donor group. In this reaction, the first step by tyrosine hydroxylase is the rate-limiting step for biosynthesis of catecholamines.

Figure: Synthesis of Catecholamines

(Source: Klabunde 2012)

3. Catecholamines act on heart and blood vessels in the case via alpha and beta adrenoceptors. Catecholamines include adrenaline, noradrenaline and dopamine. These are neurotransmitters, released in the synaptic junctions, where they act as stimuli of stress response by the brain. Catecholamines act on alpha and beta adrenergic receptors, after releasing response against stress (Sorriento et. 2012). Catecholamines enhance the heart beat rate, by narrowing blood vessels and by causing rise in blood pressure. The major reason behind  catecholamine related heart beat increases the enhancement of intracellular concentration of cyclic-AMP. The beta1 enhances the concentration of intracellular cycle-AMP (Kuchel et al. 2012). The cyclic-AMP is a secondary messenger, which acts on the activity of protein kinase A. The PKA is a kinase, which has a property of adding phosphate group on its substances, thereby activating those substances. The activated protein kinase A phosphorylates some specified sites of calcium channels, which also includes alpha1-subunits. The phosphorylation of calcium channels modifies the composition and helps the channels to open. . The open calcium channels allow calcium ions to enter. The enhanced concentration of intracellular calcium ion enhances the probability of cardiac contraction. By the similar mechanism, it increases the calcium ion gathered by sarcoplasmic reticulum. The result would be the enhanced amount of calcium stored in the intracellular endoplasmic reticulum (Manger and Gifford 2012). Hence, this also enhances the probability of calcium ion availability in the intracellular vesicles, which could be released for potential action.. Therefore, the net result is an elevated ventricular function.

Norepinephrine is an agonist of alpha and beta-1 receptors and produces vasoconstriction without vasodilation component. As a result, direct positive inotropuc and chronotropic effects are exerted and finally it enhances peripheral vascular resistance, pulse pressure and arterial pressure. Epinephrine is an agonist of alpha and beta receptors. It enhances vasodilation and vasoconstriction (Michalkiewicz 2013). The effects of resulted inotrophic and chronotropic actions involve peripheral resistance and increased pulse pressure. Dopamine is the agonist of dopamine D1 receptors. However, at high concentration dopamine acts as agonist of alpha-1 receptors and enhances the release of norepinephrine from synaptic terminals. Dopamine decreases peripheral vascular resistance and increases pulse pressure and mean arterial blood pressure, by interacting with D1 receptor, which enhances vasodylation. The beta-induced enhancement in stroke volume and heart rate resulted  in high cardiac output and raised systolic BP and enhanced pulse pressure (Mooren 2012).

Role of Catecholamines in Blood Pressure Regulation

4. The presence of catecholamines in plasma indicates the level of stress in the patient. Being the stress hormone, the effect of these hormones is significant in examining the case of blood pressure and hypertension. The Catecholamine Urine Test is used for identifying signs of pheochromocytoma. Sometimes this kind of tumor grows in the adrenal gland and promotes the synthesis of catecholamines (Oemisch 2012). Sometimes, it would help to detect the presence of neuroblastoma, however, this kind of tumors are more common in children. However, in case of Miss Chan, doctors have prescribed for catecholamine urine test to detect the presence of pheochromocytoma. This tumor enhances the release of hormones from adrenal glands in response to stress, it can cause high blood pressure, excessive sweating, rapid heartbeats, all of these signs are present in Miss Chan, so the suggestion for this test to Miss Chan is an appropriate diagnosis. The result showed elevated levels of catecholamines concentration in blood plasma and urine of Miss Chan. The result showed that, Miss Chan has 6175 nmol/24 hrs of metanephrine in her urine sample, whereas the normal range is 375 to 1506 nmol/24 hrs. It is indicting that, Miss Chan is having excessive amount of metabolic products of such hormones in her urine sample (Radermacher et al. 2013). It indicates that, there are some irregularities in hormonal balance, and these stress hormones are the major reason behind her symptoms of acute chest pain, high blood pressure, anxiety and increased pulse rate. Therefore, there is a chance of the presence of a pheochromocytoma tumor. The result would be confirmed with further tests.

5. In the case of Miss Chan, her blood plasma and urine samples were tested for measuring the amount of stress hormones in body fluids. The presence of elevated levels of stresses hormones and its derivates indicate that some hormone imbalance is created in the body, thereby enhancing the formation and release of stress hormone from the adrenal gland (Santiago 2012). The primary catecholamines are broken down into the metabolic metanephrines and normetanephrines. The metanephrine is a metabolic derivative of the result, which indicates the presence of stress hormones or catecholamines. Therefore, the presence of metanephrine in the urine indicates the secretion of excessive amount of catecholamines, which enhances blood pressure and pulse rates along with additional symptoms (Wenzel et al. 2012). The elevated level of metanephrine in blood indicates the presence of pheochromocytomas, which is a rare tumor. This test would be followed by confirmatory tests, which would be applicable to Miss Chan.

Reference List

Acton, Q. (2012). Pheochromocytomas. Atlanta: Scholarly Editions.

Damanhuri, M. (2012). Catecholamines and stress. North Ryde, N.S.W.: Macquarie University.

Eiden, L. (2013). Catecholamine research in the 21st Century. London: Academic Press.

Eiden, L. (2013). Catecholamine research in the 21st Century. London: Academic Press.

Eleftheriou, B. and Scott, J. (2012). Physiology of Aggression and Defeat. Boston: Springer US.

Goldstein, D. (2013). Plasma catecholamines and essential hypertension. An analytical review. Hypertension, 5(1), pp.86-99.

Ice, G. and James, G. (2012). Measuring stress in humans. Cambridge: Cambridge University Press.

Klabunde, R. (2012). Cardiovascular physiology concepts. Philadelphia, PA: Lippincott Williams & Wilkins/Wolters Kluwer.

Klabunde, R. (2012). Cardiovascular physiology concepts. Philadelphia, PA: Lippincott Williams & Wilkins/Wolters Kluwer.

Kuchel, O., Buu, N. and Serri, O. (2012). Sulfoconjugation of catecholamines, nutrition, and hypertension. Hypertension, 4(5_Pt_2), pp.III93-III93.

Manger, W. and Gifford, R. (2012). Pheochromocytoma. New York: Springer New York.

Michalkiewicz, M. (2013). Response: Hypotension and Reduced Catecholamines in Neuropeptide Y Transgenic Rats. Hypertension.

Mooren, F. (2012). Encyclopedia of Exercise Medicine in Health and Disease.

Oemisch, M. (2012). Contribution of catecholamines to visual working memory in the macaque monkey. Kingston, Ont.: [publisher not identified].

Radermacher, P., Huber-Lang, M. and Thiemermann, C. (2013). Catecholamines and the Septic Heart. Shock, 39(4), pp.404-405.

Santiago, J. (2012). Determination of catecholamine induced changes in vascular connexin function and expression.

Sorriento, D., Santulli, G., Del Giudice, C., Anastasio, A., Trimarco, B. and Iaccarino, G. (2012). Endothelial Cells Are Able to Synthesize and Release Catecholamines Both In Vitro and In Vivo. Hypertension, 60(1), pp.129-136.

Wenzel, U., Stange, D. and Dasing, R. (2012). A simple test to appreciate compliance with antihypertensive drug therapy. Journal of Hypertension, 30(3), p.624.