Renin-Angiotensin-Aldosterone System


The renin-angiotensin-aldosterone system (RAAS) plays a physiological role in regulating blood volume and systemic vascular resistance. The two together have an influence on cardiac output and arterial blood pressure. There are three important components to the RAAS; renin, angiotensin, and aldosterone.

Stimulation of renin from the juxtaglomerular cells (JG) is stimulated by sympathetic nerve activation through B1-adrenoceptors, renal hypotension or decreased sodium in the distal tubules of the kidney. A reduction in blood pressure in the afferent arterioles causes release of renin, and conversely increased arteriole pressure inhibits renin release. Specialized cells of the distal tubules; the macula densa sense the concentration of sodium and chloride ions in normal tubular fluid. When NaCl ions are elevated, renin is inhibited, and when there is a reduction in tubular NaCl the JG is stimulated to release renin. When arteriole pressure is reduced, there is a decreased GFR. The decreased GFR reduces NaCl in the distal tubule which is an important mechanism contributing to renin release.

Renin acts upon the substrate angiotensinogen the undergoes cleavage to form angiotensin I. The vascular endothelium has an enzyme; angiotensin converting enzyme (ACE), that cleaves angiotensin I to form angiotensin II. Angiotensin II carries out several important functions; it causes vasoconstriction resulting in systemic vascular resistance and increase in arterial pressure. It also stimulates sodium reabsorption that increases the sodium and water retention in the body. It acts on the adrenal cortex to release aldosterone. It stimulates the release of vasopressin otherwise known as antidiuretic hormone that increases fluid retention in the kidneys. It stimulates thirst because of the amount of sodium being reabsorbed. Lastly it stimulates cardiac hypertrophy.

The RAAS is not only regulated by internal inhibition and stimulation, but by natriuretic peptides (NPs) that are synthesized in the heart, brain and other organs. The physiological function of NPs is too decrease blood volume and systemic vascular resistance. NPs increase the glomerular filtration rate which causes increased sodium excretion (natriuresis) and increased fluid excretion (diuresis). They also inhibit renin release and decrease circulating levels of angiotensin II and aldosterone. This results in systemic vasodilation.


General Endocrinology

Hormones make up the endocrine system and act on almost every tissue in the body. Hormones are substances that are produced by a specialized cell that circulates in the blood. The best example of this is insulin which is secreted by the beta cells in the pancreas.


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There are multiple forms of chemical signaling that hormones utilize. The first is autocrine where the cell targets itself. Signaling across gap junctions occurs when a specialized cell targets another cell that is connected via a gap junction. Paracrine is when the targeted cell is nearby. Endocrine which will be the primary focus for today is when the cell produces hormones or chemical signals that have to travel through the blood stream to act on distant cells. Depending on the receptor type to these hormones distinguishes the action it has on the recipient tissue or cell. Receptors can by cytoplasmic, ion channels, tyrosine kinase receptors, or a G-protein coupled receptor. There can also be different types of hormones. Protein hormones utilize calcium as a secondary messenger. The action potential of protein hormones is quick as opposed to steroid hormones. The action of steroid hormones is slow as steroids are not as membrane permeable as protein hormones. Its important to note that hormones are released in pulses. Each pulse has an amplitude and period.

The endocrine system needs feedback control loops to function properly. Negative control loops maintain hormonal balance. Positive control loops are actually what causes physiological changes in the tissues involved.

The endocrine system starts in the hypothalamus. The hypothalamus releases releasing hormones to stimulate the anterior and posterior pituitary to secrete effector hormones that act on various sites of the body.

The anterior pituitary otherwise known as the adenohypophysis secretes the majority of the hormones. Releasing hormones are secreted by the hypothalamic neurons into the hypothalamopituitary portal system. These hormones are then carried down the pituitary stalk by this portal system into the adenohypophysis. The anterior pituitary secretes adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These all act on their respectable tissues/cells to secrete specific hormones. ACTH acts on the adrenal gland, which sits on top of the kidneys. The adrenal gland is responsible for secretion of catecholamines (epinephrine/norepinephrine) that influences the flight or fight response as well as glucocorticoids such as cortisol which have physiological effects throughout the entire body. TSH acts on the thyroid gland to secrete the thyroid hormones T3 and T4. These hormones also have wide-spread physiological function throughout the body. GH acts on the liver and influences bone, muscle, and tissue growth. PRL acts on the mammary glands such as the breast glands to stimulate growth and to start lactation. FSH and LH act on the testes of males to secrete inhibin and testosterone as well on the ovaries in females to secrete estrogen, progesterone, and inhibin. Decreased or elevated levels of any of these hormones can have detrimental effects on normal physiological processes. These discrepant levels can either be from primary disease (In the organ where the hormones are produced) or it can be secondary disease, i.e. from the hypothalamus, or pituitary.

Oxytocin and vasopressin (ADH) are the hormones secreted by the posterior or neurohypophysis pituitary. These are synthesized in the paraventricular supraoptic nuclei of the hypothalamus and are carried down the pituitary stalk by axonal transport. These hormones are then released into the general circulation in the neurohypophysis. Oxytocin works in females and males. It effects the uterine smooth muscle and mammary glands in females and in males it effects the smooth muscle in the ductus deferens and the prostate gland. Vasopressin or ADH promotes water retention in the distal tubules and collecting ducts of the kidneys. SIADH is excess ADH secretion and results in concentrated urine, and a low serum concentration. In other words there is low serum sodium which is bad! Diabetes insipidus on the other hand is deficiency in ADH.