Control of water excretion regulation of plasma osmolarity

Regulation of the osmolarity of extracellular fluid, including that of the plasma, is necessary in order to avoid osmotically induced changes in intra-cellular fluid volume. If the extracellular fluid were to become hypertonic (too concentrated), water would be pulled out of the cells; if it were to become hypotonic (too dilute), water would enter the cells. The osmolarity of extracellular fluid is maintained at 290 mOsm/l by way of the physiological regulation of water excretion. As with sodium, water balance in the body is achieved when water intake is equal to water output. Sources of water input include:

• Metabolically produced water

Sources of water output include:

• Loss from the lungs and nonsweating skin

The two factors controlled physiologically in order to maintain water balance include fluid intake and urine output. Fluid intake is largely influenced by the subjective feeling of thirst, which compels an individual to ingest water or other fluids. Urine output is largely influenced by the action of ADH, which promotes the reabsorption of water from the distal tubule and the collecting duct. Thirst and ADH secretion are regulated by the hypothalamus, of which three functional regions are involved:

• Osmoreceptors

• Thirst center

• ADH-secreting cells

The osmoreceptors of the hypothalamus monitor the osmolarity of extracellular fluid. These receptors are stimulated primarily by an increase in plasma osmolarity; they then provide excitatory inputs to the thirst center and the ADH-secreting cells in the hypothalamus. The stimulation of the thirst center leads to increased fluid intake. The stimulation of the ADH-secreting cells leads to release of ADH from the neurohypophysis and, ultimately, an increase in reabsorption of water from the kidneys and a decrease in urine output. These effects increase the water content of the body and dilute the plasma back toward normal. Plasma osmolarity is the major stimulus for thirst and ADH secretion; two additional stimuli include:

• Decreased extracellular volume

• Angiotensin II

A more moderate stimulus for thirst and ADH secretion is a decrease in extracellular fluid, or plasma volume. This stimulus involves low-pressure receptors in the atria of the heart as well as baroreceptors in the large arteries. A decrease in plasma volume leads to a decrease in atrial filling, which is detected by low-pressure receptors, and a decrease in MAP, which the baroreceptors detect. Each of these receptors then provides excitatory inputs to the thirst center and to the ADH-secreting cells.

Angiotensin II also stimulates the thirst center to increase the urge to ingest fluids, and ADH secretion to promote reabsorption of water from the kidneys. Other factors influencing ADH-secreting cells (but not the thirst center) include pain, fear, and trauma, which increase ADH secretion, and alcohol, which decreases it.

Pharmacy application: drug-related nephropathies

Drug-related nephropathies involve functional or structural changes in the kidneys following the administration of certain drugs. The nephrons are subject to a high rate of exposure to substances in the blood due to the high rate of renal blood flow and the substantial glomerular filtration rate. Furthermore, the kidneys may be involved in the metabolic transformation of some drugs and therefore exposed to their potentially toxic end-products.

Elderly patients are particularly susceptible to kidney damage due to their age-related decrease in renal function. Also, the potential for nephrotoxicity is increased when two or more drugs capable of causing renal damage are administered at the same time. Drugs and toxic end-products of drug metabolism may damage the kidneys by way of the following mechanisms:

• Decrease in renal blood flow

• Direct damage to the tubulointerstitial structures

• Hypersensitivity reactions

Nonsteroidal anti-inflammatory drugs (NSAIDs) may damage renal structures, in particular, the interstitial cells of the medulla. Prostaglandins E2 and I2 are vasodilators that help to regulate renal blood flow under normal physiological conditions. Because NSAIDs inhibit the synthesis of prostaglandins, renal damage likely results from an inappropriate decrease in renal blood flow. Chronic analgesic nephritis (inflammation of the nephrons) is associated with analgesic abuse; ingredients such as aspirin and acetaminophen have been implicated in this disorder.

Acute drug-related hypersensitivity reactions (allergic responses) may cause tubulointerstitial nephritis, which will damage the tubules and interstitium. These reactions are most commonly observed with administration of methicillin and other synthetic antibiotics as well as furosemide and the thiazide diuretics. The onset of symptoms occurs in about 15 days. Symptoms include fever, eosinophilia, hematuria (blood in the urine), and proteinur-ia (proteins in the urine). Signs and symptoms of acute renal failure develop in about 50% of the cases. Discontinued use of the drug usually results in complete recovery; however, some patients, especially the elderly, may experience permanent renal damage.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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