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TABLE 15-1 Hormones That Are Produced or Have Major Actions in the Kidney

Hormones

Major target organ(s)

Function(s)

Produced by the kidney Erythropoietin la,25-Dihydroxyvitamin D3

(+other vitamin D metabolites) Renin (an enzyme)"

Prekallikreins Prostaglandins

Acting on the kidney Aldosterone

Atrial natriuretic factor (ANF)

la,25-Dihydroxyvitamin D3

Endothelins

Vasopressin

Prostaglandins

Catecholamines (epinephrine, norepinephrine) Cortisol Insulin Glucagon Thyroxine

Bone marrow Intestine, bone, kidney

Blood to mediate production of the hormonal angiotensins Serum protein a2-globulins Kidney

Stimulate red blood cell formation

Maintenance of calcium homeostasis and regulation of gene transcription in many target organs To mediate production of aldosterone (by the adrenal cortex)

To produce kinins (e.g., bradykinin) that are potent vasodilators To antagonize hypertension by inhibiting Na+ reabsorption

Stimulate Na+ reabsorption Increase glomerular filtration rate Stimulate Ca2+ reabsorption (Secondary actions) Promote H20 reabsorption

Diverse Diverse Diverse Diverse

1 Technically renin, an enzyme, does not fit the classical or modern definition of a hormone (see Chapter 1).

physiological network of the living organism, in that it functions as the ultimate organ for the monitoring and conservation of body water and all its electrolyte constituents, as well as many small organic molecules. In addition, the kidney plays an important physiological role in maintaining correct acid-base balance. It is thus perhaps not surprising to see concentrated in the kidney such an array of hormone production sites, as well as sites of hormone action. It seems likely that the exquisite anatomical organization of the kidney (discussed later) offers significant advantages to the organism in terms of the regulation of production of key hormones, as well as the regulation of the biological responses to various hormones that affect the homeostasis of key bodily electrolytes.

Many aspects of these processes are also closely linked to the process of blood pressure regulation. Accordingly, a secondary objective of this chapter is to consider hormonal aspects of the cardiovascular system. Table 15-2 summarizes the endocrine aspects of the cardiovascular system.

B. Scope of This Chapter

It is not pedagogically feasible to present a description of the physiological participation of the kidney in the formation of urine, namely, glomerular filtration and determination of electrolyte and acid-base balances. Also, it is beyond the scope of this book to present a detailed consideration of the heart and cardiac physiology and function. Thus, after a brief review of the anatomy of the kidney and the cardiovascular system, this chapter will present separately the renin-angiotensin-aldosterone-atrial natriuretic factor-Na+ reabsorption system, the endothelin system, the kallikrein-kinin system, and the nitric oxide system. Finally, this chapter also provides a brief introduction to the topics of the hormones related to blood cell production and the hormones associated with the inflammation process.

A portion of the renin-angiotensin-aldosterone system, particularly that involving the biosynthesis and secretion of aldosterone, is included in Chapter 10. The roles of the kidney in calcium and phosphorus homeostasis, including its production of key vitamin D metabolites and its action as a target organ for parathyroid hormone, calcitonin, and la,25-dihydroxyvi-tamin D3, are covered in Chapter 9.

II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS

A. The Kidney

1. Introduction

The kidneys, along with the ureters, urinary bladder, and male or female urethra, comprise the anatomical units responsible for the multiplicity of endocrine,

TABLE 15-2 Hormones That Are Produced by or Have a Major Action on the

Cardiovascular System"'6

Hormones

Major target organ(s)

Function(s)

Produced by cardiovascular system Atrial natriuretic hormone (ANF) Endothelins (ET-1, ET-2, ET-3)

Nitric oxide (NO)

Acting on the cardiovascular peripheral system Endothelins Angiotensin II Vasopressin

Prostaglandins (thromboxanes)

Epinephrine, norepinephrine

Bradykinin

Nitric oxide

Atrial natriuretic factor

Kidney glomerulus Endothelial tissue Brain

Vascular smooth muscle

Increase filtration rate Vasoconstriction

Vasorelaxation

Vasoconstriction

Vasoconstriction

Vasoconstriction

Vasoconstriction

Vasoconstriction

Vasorelaxation

Vasorelaxation

Vasorelaxation

" The cardiovascular system comprises the heart and the arterial and venous circulatory systems; see Figure 15-6. b This table excludes hormones that are produced in the blood (e.g., angiotension) and hormones that use blood components as substrates (e.g., renin).

metabolic, and filtering actions of the kidney. Figure 10-1 presents a gross anatomical overview of the urinary system. With the completion of the metabolic and filtration actions of the kidneys, the urine, containing a wide variety of bodily wastes, is conveyed via the two ureters (one per kidney) to the urinary bladder for temporary storage. Then, at the time of micturition or emptying of the urinary bladder, the urine is voided through the urethra. The normal output of urine per day in adults may range from 600 to 2500 ml. Table 15-3 lists the principal electrolytes of the intracellular and extracellular fluids and urine.

2. Kidney —Gross Structure

The two kidneys in humans are located in a posterior position in the abdominal cavity; they present a "beanlike" appearance and are enclosed in a fibrous capsule. Diagrammed in Figure 15-1 is the cross-sectional appearance of the kidney. In the central portion of the concave border is the hilus, which contains all of the blood vessels and nerves for the kidney as well as the ureter. There are three general regions of the kidney: the renal pelvis, the renal cortex, and the renal medulla. The renal pelvis, which is attached to the upper end of the ureter, receives or collects the urine from all regions of the kidney. The renal medulla, which is the inner portion of the kidney, is composed of cone-shaped renal masses termed renal pyramids. The renal cortex constitutes the outer portion of the kidney.

3. Kidney Microscopic Structure

The fundamental operational unit of the kidney is the nephron (see Figure 15-2). Each human kidney contains ~1 million nephrons. The nephron is the anatomical structure responsible for the formation of the urine as a consequence of the filtration of the blood and concomitant associated selective absorption and secretion of constituents in the newly created urine.

Each nephron consists of a renal tubule (largely in the medulla) and a renal corpuscle (located in the cortex). The renal corpuscle (see Figure 15-3), in turn, is composed of a glomerulus enclosed by a capsule, termed Bowman's capsule. The glomerulus is an exquisite anatomical structure containing a group of capillaries interposed between two arterioles. The vessel transporting blood to the glomerulus is known as the afferent arteriole; it divides into 40-60 capillary loops, which then ultimately reunite to form the exit pathway for the blood known as the efferent arteriole. Associated with the cells of the efferent arteriole (see Figure 15-3) is a cluster of cells termed the juxtaglomerular or JG cells. The JG cells are the site of production of the enzyme renin. As noted in Figure 15-2, the efferent arterioles subsequently arborize to form a network of capillaries surrounding the renal tubule.

Bowman's capsule constitutes the beginning of the renal tubule. Specialized cells, termed podocytes, in Bowman's capsule form slits or pores of such molecular dimensions that restrict and effectively prevent the passage of macromolecules in the blood into the top of the nephron; thus, only small molecules pass into the filtrate.

The renal tubule (see Figure 15-2) is anatomically structured to permit countercurrent distributive processes between its proximal and distal regions and

TABLE 15-3 Principal Constituents of Major Body Fluids in the Normal Adult

Constituent

Intracellular compartment (meq/liter)

Extracellular compartment (meq/liter)"

Urine6 (g)e

Urine ratio [plasma]

Cations Sodium Potassium Calcium Magnesium Anions Chloride Bicarbonate Phosphate (HP042 ) Sulfate (SO,2") Other Protein Urea

Creatinine Organic acids Glucose (mg/100 ml)

0 0

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