Principles and Practice of Pediatric Nephrology Vijayakumar M, Nammalwar BR
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1Basic Nephrology2

Structure and Functions of the Kidneys1

Nammalwar BR,
Vijayakumar M
 
INTRODUCTION
The kidney maintains the extracellular volume, osmoregulation, electrolyte and acid-base balance. It regulates the arterial blood pressure, calcium, phosphorus and magnesium metabolism, removes the metabolic nitrogenous waste products, toxins, drugs and is responsible for the production of hormones, vitamin D, erythropoietin, renin and vasoactive amines.
 
GROSS ANATOMY
The kidneys are paired organs that lie on the posterior wall of the abdomen behind the peritoneum on either side of the vertebral column. The kidneys grow rapidly in the first year of life, from 4.5 cm in length at birth to 6.5 cm in childhood and to 11 cm in adulthood. The renal artery and vein, nerves and pelvis enter the kidney on the medial side (Fig. 1.1). The renal tissue is divided into outer region, the cortex and the inner medulla and is composed of nephrons, blood vessels, lymphatics and nerves. The medulla in the human kidney is divided into conical masses called renal pyramids with the intervening renal columns. The base of the pyramids originates at the corticomedullary border and the apices are the papillae, which project into the minor calyces, wherein urine is collected from the papillae. The minor calyces are cup-like structures joining within the kidney to form three or four major calyces. The major calyces in turn unite to form the pelvis, the upper expanded region of the ureter, which carries urine to the urinary bladder 4(Fig. 1.2). The walls of the calyces, pelvis and ureters contain smooth muscle that contracts to propel the urine towards the urinary bladder.
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Fig. 1.1: Anatomy of the kidney and ureters in relation to the vascular system
 
Renal Vascular System
The renal artery divides into five segments, which subsequently branches up the sides of the pyramids to form the interlobar artery, arcuate artery, interlobular artery and the afferent arteriole, which leads to glomerular capillaries (Fig. 1.3). The glomerular capillaries come together to form the efferent arteriole, which leads into a second capillary network, the peritubular capillaries, which supply blood to the nephron. The vessels of the venous system run parallel to the arterial vessels and progressively form the interlobular, arcuate, interlobar and renal vein.
 
Nervous System
Sympathetic fibers originate in the lower splanchnic nerves and travel through the lumbar ganglion to the kidney. Stimulation of the sympathetic nervous system reduces renal blood flow by causing intrarenal vasoconstriction. It also stimulates the local renin-angiotensin-aldosterone system and enhances sodium reabsorption.
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Fig. 1.2: Cut section of the kidney with features of renal parenchyma
 
STRUCTURE AND FUNCTIONS OF THE NEPHRON
The gross functions of the kidney are:
  1. Regulates the osmotic pressure (osmolality) of the body fluids by excreting osmotically dilute or concentrated urine.
  2. Regulates the concentrations of numerous ions in blood plasma, including Na+, K+, Ca++, Mg++, Cl, HCO3, phosphate and sulfate.
  3. Regulates acid-base balance by excreting H+ when there is excess acid or HCO3 when there is excess base.
  4. Regulates the volume of the extracellular fluid (ECF) by controlling Na+ and water excretion.
  5. Regulates arterial blood pressure by adjusting Na+ excretion and producing various substances (e.g. renin) that can affect blood pressure.
  6. Eliminates the waste products of metabolism, such as urea, the main nitrogen-containing end product of protein metabolism in humans; uric acid, the end product of purine metabolism and creatinine, the end product of muscle degradation.
  7. Eliminates drugs and toxic compounds.
  8. They are the major sites of production of certain hormones, including erythropoietin and 1,25-dihydroxyvitamin D3.
  9. 5They degrade several polypeptide hormones, including insulin, glucagon and parathyroid hormone.
  10. They synthesize ammonia, which plays a role in acid-base balance.
  11. They synthesize substances that affect renal blood flow and Na+ excretion, including arachidonic acid derivatives, prostaglandins, thromboxane A2 and kallikrein, a proteolytic enzyme that results in the production of kinins.
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Fig. 1.3: Cut section of the kidney with diagrammatic presentation of the renal blood supply
The functional unit of the kidneys is the nephron. Each human kidney contains approximately 1.2 million nephrons. The nephron consists of a glomerulus, proximal tubule, loop of Henle, distal tubule and collecting duct system (Fig. 1.4). The glomerulus is responsible for filtering the blood, providing a barrier to the passage of protein and cells into the urine. The glomerulus consists of a network of capillaries supplied by the afferent arteriole and drained by the efferent arteriole. The glomerular capillaries press into the closed end of the proximal tubules, forming capsule of Bowman of the glomerulus. The capillaries are covered by epithelial cells, called podocytes, which form the visceral layer of the capsule of Bowman. The visceral cells continue at the vascular pole to form the parietal layer of the capsule of Bowman. The space between the visceral and the parietal layer is the Bowman's space, which at the urinary pole of the glomerulus becomes the lumen of the proximal tubule (Fig. 1.5). The endothelial cells of the glomerular capillaries are covered by a basement membrane, which is surrounded by podocytes. The capillary endothelium, basement membrane and foot process of podocytes form the filtration barrier. The endothelium is fenestrated and is freely permeable to water, small solutes and most proteins, but not permeable to cellular components. The endothelial cells have negatively-charged glycoproteins on their surface, which retard the filtration of negatively-charged proteins 6into Bowman's space. The endothelial cells synthesize a number of vasoactive substances, angiotensin, prostaglandins, nitric acid, endothelin-1, bradykinins and glucocorticoids that are important in controlling renal flow. The basement membrane, which is a porous matrix of negatively-charged proteins including type-IV collagen, laminin, the proteoglycans agrin, perlecan and fibronectin, is an important filtration barrier to plasma proteins. The basement membrane functions primarily as charge-selectivity filter allowing proteins to cross on the basis of electrical charge. The podocytes have long finger-like process that interdigitate to cover the basement membrane and are separated by apparent gaps called filtration slits. Each filtration slit is bridged by a thin diaphragm, which contains pores (Fig. 1.6). The filtration slit diaphragm is composed of several proteins including nephrin, podocin, alpha-actinin 4 and CD2-associated protein (CD2AP). Filtration slit diaphragm, which function primarily as the size-selective filter, retard the filtration of proteins and macromolecules that cross the basement membrane from entering Bowman's space. In addition to the phagocytosis of the proteins, podocytes have a well-developed Golgi apparatus, used to produce and maintain the glomerular basement membrane.
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Fig. 1.4: Diagrammatic presentation of segments of the nephron
7
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Fig. 1.5: Diagrammatic presentation of structure of the glomerulus
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Fig. 1.6: Electron microscopic presentation of glomerular capillary wall showing the components of the filtration barrier
Nephrons is classified into superficial and juxtamedullary. The glomerulus of each superficial nephron is located in the outer region of the cortex. Its loop of Henle is short and its efferent arteriole branches into peritubular capillaries that surround the nephron segments of its own and adjacent nephrons. This capillary network serves as a pathway to deliver substances to the nephron for secretion and return of reabsorbed water and solutes to the circulatory system. The glomerulus of juxtamedullary nephron is located at the corticomedullary junction and has long loop of Henle, which extend deep into the medulla. The efferent arteriole forms both a network of peritubular capillaries and also number of vascular loop called vasa recta, deep in the medulla. The long loop of Henle and its vasa recta serve in concentrating and diluting the urine. The proximal tubule initially forms several coils, followed by a straight piece that descends towards the medulla. The next segment is the loop of Henle, which is composed of the straight part of the proximal tubule, termed as descending thin limb, which end in a hairpin turn, followed by ascending thin limb and thick ascending limb. At the end of the ascending limb, where nephron passes between the afferent and efferent arterioles of the same nephron is the juxtaglomerular apparatus. This is made up of an area of thickened epithelial cells of the afferent arteriole, the granular cells. They manufacture, store and release renin. Renin is involved in the formation of angiotensin II and ultimately aldosterone. The area of specialized cells lining the wall of the distal tubule is the macula densa and the extraglomerular mesangial cells (Fig. 1.7). The juxtaglomerular apparatus activates the renin-angiotensin-aldosterone and sodium conservation process. The distal tubule is joined by two or more nephrons to form a cortical collecting duct, which later becomes the medullary collecting duct. Numerous collecting ducts from the 8nephrons join and open by way of the duct of Bellini into minor calyx at the papillary tip of the pyramid (Figs 1.2 and 1.4).
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Fig. 1.7: Diagrammatic presentation of juxtaglomerular apparatus
After its production in the glomerulus, the filtrate enters the tubule, which functions to reabsorb and secrete fluid and electrolytes to adjust the urinary composition to maintain homeostasis of body fluid. Each nephron segment has specific transport functions (Table 1.1). Almost all cells in the nephron, have a single non-motile primary cilium, which protrudes into tubule fluid. Primary cilia are mechanosensors, which sense changes in the flow rate of tubule fluid and chemosensors, sense or respond to compounds in the surrounding fluids and initiate Ca-dependent signaling pathways including those that control kidney cell function, proliferation, differentiation and apoptosis. The process of reasborption of solutes, electrolytes and water from the tubular fluid to blood across the renal tubular cell membrane and secretion from the peritubular capillary blood to tubular fluid is the result of specialized membrane carrier proteins called ‘transporters’, channels or by diffusion. Active transporters are 9Na+/K+-ATPase, Ca++-ATPase, H+-K+-ATPase and H+ ATPase. The passive transporters are Na+/K+/Cl and Na+/glucose cotransporters and Ca++/Na+ and H+/Na+ exchanger.
Table 1.1   Tubular functions
Sites
Function
Reabsorption
Secretion
Proximal tubule
Bicarbonate (80%)
Calcium (70%)
Phosphorous (80%)
Magnesium (15%)
Potassium (67%)
Proteins as amino acids (100%)
Sodium and chloride (67%)
Urea (67%)
Water (67%)
Loop of Henle
Thin descending limb
Water (15%)
Urea
Thin ascending limb
Sodium chloride (25%)
Thick ascending limb
Bicarbonate (10%)
Magnesium (60%)
Potassium (20%)
Ammonium (variable)
Calcium (20%)
Sodium chloride (25%)
Distal tubule
Bicarbonate (10%)
Calcium (9%)
Magnesium (5%)
Phosphorus (10%)
Sodium chloride (5%)
Collecting duct
Bicarbonate (4%)
Ammonium (variable)
Potassium (nil)
Bicarbonate in metabolic alkalosis
Sodium chloride (3%)
Potassium (0%–70%)
Urea (variable)
Urea (variable)
Water (variable)
Courtesy: Koeppen BM, Stanton BA. Renal Physiology. Mosby; 2007
BIBLIOGRAPHY
  1. Mehta KS. Anatomy of human kidneys. In: Nammalwar BR, Vijayakumar M (Eds). Principles and Practice of Pediatric Nephrology, 1st edition. Jaypee Brothers Medical Publishers (P) Ltd;  New Delhi:  2004. pp. 3–7.
  1. Mehta KS. Basic renal physiology. In: Nammalwar BR, Vijayakumar M (Eds). Principles and Practice of Pediatric Nephrology, 1st edition. Jaypee Brothers Medical Publishers (P) Ltd;  New Delhi:  2004. pp. 8–14.
  1. Eaton DC, Pooler J. Vander's Renal Physiology, 7th edition. McGraw Hill;  New York:  2009.
  1. Koeppen BM, Stanton BA. Renal Physiology, 4th edition. Mosby;  Philadelphia:  2009.