Chapter 174

### INTRODUCTION

The kidney is a complex network of approximately two million nephrons that are involved in several regulatory and homeostatic functions. Each nephron consists of a glomerulus and a tubule that empties into a collecting duct. Urine is formed by glomerular ultrafiltration, and tubular reabsorption and secretion. The nephron regulates hormones that contribute to fluid homeostasis, bone metabolism, and hematopoiesis.

### THE NEPHRON

The glomerulus is composed of capillaries that feed into the Bowman’s capsule. Blood enters through the afferent arteriole and is drained by the efferent arteriole. The endothelial cells and epithelial cells provide an effective filtration barrier for large molecular weight substances and negatively charged molecules due to the net negative charge of the barrier. Therefore, the filtration barrier is both size selective and charge selective. Mesangial cells contain contractile proteins and respond to various stimuli and regulate filtration.

The main function of the proximal tubule is the reabsorption of Na+ by active transportation. Water and Cl usually follow Na+ passively. About 65%-75% of Na+, water, and Cl are reabsorbed. Na+ reabsorption is also coupled with the secretion of hydrogen ions and reabsorption of 90% of filtered bicarbonate ions. Glucose and amino acids are completely reabsorbed. The proximal tubule also secretes organic cations, such as creatinine.

About 25%-35% of the ultrafiltrate reaches the loop of Henle. Here 15%-20% of the filtered Na+ is reabsorbed. Some Ca2+ and Mg2+ reabsorption also takes place here.

The distal tubule has very tight junctions and is comparatively impermeable to water and Na+. The distal tubule is the major site of parathyroid hormone-regulated Ca2+ reabsorption. The latter end of the distal tubule, unlike the proximal part, participates in aldosterone-mediated Na+ reabsorption.

The juxtaglomerular apparatus is a specialized area of the afferent arteriole and the ascending segment of the loop of Henle, the macula densa. Juxtaglomerular cells contain renin and are innervated by the sympathetic nervous system. Release of renin depends on beta adrenergic stimulation, changes in afferent arteriolar wall pressure, and changes in Cl- flow past the macula densa. Renin acts on angiotensinogen, produced in the liver to form angiotensin I. This is converted in the lungs by angiotensin converting enzyme to form angiotensin II that is responsible for blood pressure regulation and aldosterone secretion. Collectively, this mechanism is termed the renin–angiotensin system.

### RENAL BLOOD FLOW

The volume of blood delivered to the kidney is approximately 20%-25% of cardiac output. This amounts to 1.1-1.5 L/min in a 70 kg man. When determining renal blood flow (RBF), clearance is often calculated. The clearance of a substance is the volume of blood that is completely cleared off that substance per unit time. P-aminohippurate (PAH) clearance is utilized in the measurement of RBF and is as follows:

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