The functions of the kidney:

The functions of the kidney: After reading this lecture you should be able to.. 1. List the main functions of the kidney. 2. Know the basic physiological anatomy of the kidney and the nephron 3. Describe the steps of urine formation. 4. Define the net filtration pressure and show the forces that act on filtration membrane. The functions of the kidney are: 1. Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites. The kidneys are the primary means for eliminating waste products of metabolism that are no longer needed by the body. These products include urea (from the metabolism of amino acids), creatinine (from muscle creatine), uric acid (from nucleic acids), end products of hemoglobin breakdown (such as bilirubin), and metabolites of various hormones. These waste products must be eliminated from the body as rapidly as they are produced. The kidneys also eliminate most toxins and other foreign substances that are either produced by the body or ingested, such as pesticides, drugs, and food additives. 2. Regulation of Water and Electrolyte Balances. For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. If intake exceeds excretion, the amount of that substance in the body will increase. If intake is less than excretion, the amount of that substance in the body will decrease. 3. Regulation of Acid-Base Balance. The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. 4. Regulation of Erythrocyte Production. The kidneys secrete erythropoietin, which stimulates the production of red blood cells. One important stimulus for erythropoietin secretion by the kidneys is hypoxia. 1

5. Regulation of 1,25 Dihydroxyvitamin D3 Production. The kidneys produce the active form of vitamin D, 1,25- dihydroxyvitamin D3, by hydroxylating this vitamin at the number 1 position. 6. Glucose Synthesis. The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis. The kidneys capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver. 7. Regulation of Arterial Pressure. The kidneys play a dominant role in longterm regulation of arterial pressure by excreting variable amounts of sodium and water. The kidneys also contribute to short-term arterial pressure regulation by secreting vasoactive factors or substances, such as renin, that lead to the formation of vasoactive products. General Organization of the Kidneys and Urinary Tract The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity. Each kidney of the adult human weighs about 150 grams and is about the size of a clenched fist. The medial side of each kidney contains an indented region called the hilum through which pass the renal artery and vein, lymphatic, nerve supply, and ureter, which carries the final urine from the kidney to the bladder, where it is stored until emptied. The kidney is surrounded by a tough, fibrous capsule that protects its delicate inner structures. 2

The nephron is the functional unit of the kidney responsible for the formation of urine. Each kidney contains more than a million nephrons. A nephron consists of small tubes, or tubules, and associated small blood vessels. Fluid formed by capillary filtration enters the tubules and is subsequently modified by transport processes; the resulting fluid that leaves the tubules is urine. Renal Blood Vessels Arterial blood enters the kidney through the renal artery, which divides into interlobar arteries that pass between the pyramids through the renal columns. Arcuate arteries branch from the interlobar arteries at the boundary of the cortex and medulla. A number of interlobular arteries radiate from the arcuate arteries into the cortex and subdivide into numerous afferent arterioles, which are microscopic. The afferent arterioles deliver blood into glomeruli capillary networks that produce a blood filtrate that enters the urinary tubules. The blood remaining in a glomerulus leaves through an efferent arteriole, which delivers the blood into another capillary network the peritubular capillaries surrounding the renal tubules. This arrangement of blood vessels is unique. It is the only one in the body in which a capillary bed (the glomerulus) is drained by an arteriole rather than by a venule and delivered to a second capillary bed located downstream (the peritubular capillaries). Blood flow to the two kidneys is normally about 22 per cent of the cardiac output, or 1100 ml/min. as we said; the renal artery enters the kidney through the hilum and then branches progressively to form the radial arteries and afferent arterioles. The distal ends of the capillaries of each glomerulus coalesce to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surrounds the renal tubules. The renal circulation is unique in that it has two capillary beds, the glomerular and peritubular capillaries, which are arranged in series and separated by the 3

efferent arterioles, which help regulate the hydrostatic pressure in both sets of capillaries. High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption. By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, thereby changing the rate ofglomerular filtration, tubular reabsorption, or both in response to body homeostatic demands. Nephron Tubules The tubular portion of a nephron consists of a glomerular capsule, a proximal convoluted tubule, a descending limb of the loop of Henle, an ascending limb of the loop of Henle, and a distal convoluted tubule. 4

The glomerular (Bowman s) capsule surrounds the glomerulus. The glomerular capsule and its associated glomerulus are located in the cortex of the kidney and together constitute the renal corpuscle. The glomerular capsule contains an inner visceral layer of epithelium around the glomerular capillaries and an outer parietal layer. The space between these two layers is continuous with the lumen of the tubule and receives the glomerular filtrate. Filtrate that enters the glomerular capsule passes into the lumen of the proximal convoluted tubule. The wall of the proximal convoluted tubule consists of a single layer of cuboidal cells containing millions of microvilli; these microvilli increase the surface area for reabsorption. In the process of reabsorption, salt, water, and other molecules needed by the body are transported from the lumen, through the tubular cells and into the surrounding peritubular capillaries. The glomerulus, glomerular capsule, and convoluted tubule are located in the renal cortex. Fluid passes from the proximal convoluted tubule to the loop of Henle. This fluid is carried into the medulla in the descending limb of the loop and returns to the cortex in the ascending limb of the loop. Back in the cortex, the tubule again becomes coiled and is called the distal convoluted tubule. The distal convoluted tubule is shorter than the proximal tubule and has relatively few microvilli. The distal convoluted tubule terminates as it empties into a collecting duct. The two principal types of nephrons are classified according to their position in the kidney and the lengths of their loops of Henle. Nephrons that originate in the inner one-third of the cortex called juxtamedullary nephrons because they are next to the medulla have longer loops of Henle than the more 5

numerous cortical nephrons, which originate in the outer two thirds of the cortex. The juxtamedullary nephrons play an important role in the ability of the kidney to produce concentrated urine. A collecting duct receives fluid from the distal convoluted tubules of several nephrons. Fluid is then drained by the collecting duct from the cortex to the medulla as the collecting duct passes through a renal pyramid. This fluid, now called urine, passes into a minor calyx. Urine is then funnelled through the renal pelvis and out of the kidney in the ureter. Urine Formation Results from Glomerular Filtration, Tubular Reabsorption and Tubular Secretion The rates at which different substances are excreted in the urine represent the sum of three renal processes: (1) Glomerular filtration. (2) Reabsorption of substances from the renal tubules into the blood. (3) Secretion of substances from the blood into the renal tubules. Expressed mathematically: Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate. 6

Urine formation begins when a large amount of fluid that is virtually free of protein is filtered from the glomerular capillaries into Bowman s capsule. Most substances in the plasma, except for proteins, are freely filtered, so that their concentration in the glomerular filtrate in Bowman s capsule is almost the same as in the plasma. As filtered fluid leaves Bowman s capsule and passes through the tubules, it is modified by reabsorption of water and specific solutes back into the blood or by secretion of other substances from the peritubular capillaries into the tubules. Glomerular Filtration The glomerular capillaries have large pores in their walls, and the layer of Bowman s capsule in contact with the glomerulus has filtration slits. Water, together with dissolved solutes (but not proteins), can thus pass from the blood plasma to the inside of the capsule and the nephron tubules. The volume of this filtrate produced by both kidneys per minute is called the glomerular filtration rate (GFR). Endothelial cells of the glomerular capillaries have large pores (200 to 500 Å in diameter) called fenestrae; thus, the glomerular endothelium is said to be fenestrated. As a result of these large pores, glomerular capillaries are 100 to 400 times more permeable to plasma water and dissolved solutes than are the capillaries of skeletal muscles. Although the pores of glomerular capillaries are large, they are still small enough to prevent the passage of red blood cells, white blood cells, and platelets into the filtrate. 7

Before the filtrate can enter the interior of the glomerular capsule, it must pass through the capillary pores, the basement membrane (a thin layer of glycoproteins lying immediately outside the endothelial cells), and the inner (visceral) layer of the glomerular capsule. The inner layer of the glomerular capsule is composed of unique cells called podocytes. Each podocyte is shaped somewhat like an octopus, with a bulbous cell body and several thick arms. Each arm has thousands of cytoplasmic extensions known as pedicels, or foot processes. These pedicels interdigitate, like the fingers of clasped hands, as they wrap around the glomerular capillaries. The narrow slits between adjacent pedicels provide the passageways through which filtered molecules must pass to enter the interior of the glomerular capsule. Although the glomerular capillary pores are apparently large enough to permit the passage of proteins, the fluid that enters the capsular space contains only a small amount of plasma proteins. This relative exclusion of plasma proteins from the filtrate is partially a result of their negative charges, which hinder their passage through the negatively charged glycoproteins in the basement membrane of the capillaries. The large size and negative charges of plasma proteins may also restrict their movement through the filtration slits between pedicels. It is important to know that: 1. Filterability of Solutes Is Inversely Related to Their Size. 2. Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size. The forces that act on the glomerular membrane: These factors are depending on the glomerular membrane conditions that affect GFR. The other factors are the effects of filtration pressure. The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries. These forces include (1) Hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure), which promotes filtration. 8

(2) The hydrostatic pressure in Bowman s capsule outside the capillaries, which opposes filtration. (3) The colloid osmotic pressure of the glomerular capillary plasma proteins, which opposes filtration; and (4) The colloid osmotic pressure of the proteins in Bowman s capsule, which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman s capsule fluid is considered to be zero. Glomerular Ultrafiltrate The fluid that enters the glomerular capsule is called ultrafiltrate because it is formed under pressure the hydrostatic pressure of the blood. This process is similar to the formation of tissue fluid by other capillary beds in the body in response to Starling forces. The force favoring filtration is opposed by a 9

counterforce developed by the hydrostatic pressure of fluid in the glomerular capsule. Also, since the protein concentration of the tubular fluid is low (less than 2 to 5 mg per 100 ml) compared to that of plasma (6 to 8 g per 100 ml), the greater colloid osmotic pressure of plasma promotes the osmotic return of filtered water. When these opposing forces are subtracted from the hydrostatic pressure of the glomerular capillaries, a net filtration pressure of only about 10 mmhg is obtained. Because glomerular capillaries are extremely permeable and have an extensive surface area, this modest net filtration pressure produces an extraordinarily large volume of filtrate. The glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys per minute. The GFR averages 115 ml per minute in women and 125 ml per minute in men. This is equivalent to 7.5 L per hour or 180 L per day (about 45 gallons)! Since the total blood volume averages about 5.5 L, this means that the total blood volume is filtered into the urinary tubules every 40 minutes. Most of the filtered water must obviously be returned immediately to the vascular system, or a person would literally urinate to death within minutes. 10