S GAYATHTI GOPAKUMAR NATURAL SCIENCE ST. THOMAS TRAINING COLLEGE THIRUVANANTHAPURAM

EXCRETORY SYSTEM IN HUMANS

The excretory system is a passive biological system that removes excess, unnecessary materials from the body fluids of an organism, so as to help maintain internal chemical homeostasis and prevent damage to the body. The dual function of excretory systems is the elimination of the waste products of metabolism and to drain the body of used up and broken down components in a liquid and gaseous state. In humans and other amniotes (mammals, birds and reptiles) most of these substances leave the body as urine and to some degree exhalation, mammals also expel them through sweating. Only the organs specifically used for the excretion are considered a part of the excretory system. In the narrow sense, the term refers to the urinary system. However, as excretion involves several functions that are only superficially related, it is not usually used in more formal classifications of anatomy or function. As most healthy functioning organs produce metabolic and other wastes, the entire organism depends on the function of the system. Breaking down of one of more of the systems is a serious health condition, for example kidney failure.

URINARY SYSTEM The kidneys are large, bean-shaped organs which are present on each side of the vertebral column in the abdominal cavity. Humans have two kidneys and each kidney is supplied with blood from the renal artery. The kidneys remove from the blood the nitrogenous wastes such as urea, as well as salts and excess water, and excrete them in the form of urine. This is done with the help of millions

of nephrons present in the kidney. The filtrated blood is carried away from the kidneys by the renal vein (or kidney vein). The urine from the kidney is collected by the ureter (or excretory tubes), one from each kidney, and is passed to the urinary bladder. The urinary bladder collects and stores the urine until urination. The urine collected in the bladder is passed into the external environment from the body through an opening called the urethra.

KIDNEYS The kidney's primary function is the elimination of waste from the bloodstream by production of urine. They perform several homeostatic functions such as:1. Maintain volume of extracellular fluid

2. Maintain ionic balance in extracellular fluid 3. Maintain pH and osmotic concentration of the extracellular fluid. 4. Excrete toxic metabolic by-products such as urea, ammonia, and uric acid. The way the kidneys do this is with nephrons. There are over 1 million nephrons in each kidney; these nephrons act as filters inside the kidneys. The kidneys filter needed materials and waste, the needed materials go back into the bloodstream, and unneeded materials become urine and are gotten rid of. In some cases, excess wastes crystallize as kidney stones. They grow and can become painful irritants that may require surgery or ultrasound treatments. Some stones are small enough to be forced into the urethra.

INTERNAL ANATOMY A frontal section through the kidney reveals an outer region called the renal cortex and an inner region called the medulla. The renal columns are connective tissue extensions that radiate downward from the cortex through the medulla to separate

the

most

characteristic

features

of

the

medulla,

the renal

pyramids and renal papillae. The papillae are bundles of collecting ducts that transport urine made by nephrons to the calyces of the kidney for excretion. The renal columns also serve to divide the kidney into 6–8 lobes and provide a supportive framework for vessels that enter and exit the cortex. The pyramids and renal columns taken together constitute the kidney lobes.

Figure : Left Kidney

Renal Hilum The renal hilum is the entry and exit site for structures servicing the kidneys: vessels, nerves, lymphatics, and ureters. The medial-facing hila are tucked into the sweeping convex outline of the cortex. Emerging from the hilum is the renal pelvis, which is formed from the major and minor calyxes in the kidney. The smooth muscle in the renal pelvis funnels urine via peristalsis into the ureter. The renal arteries form directly from the descending aorta, whereas the renal veins return cleansed blood directly to the inferior vena cava. The artery, vein, and renal pelvis are arranged in an anterior-to-posterior order.

NEPHRONS AND VESSELS The renal artery first divides into segmental arteries, followed by further branching to form interlobar arteries that pass through the renal columns to reach the cortex. The interlobar arteries, in turn, branch into arcuate arteries, cortical radiate arteries, and then into afferent arterioles. The afferent arterioles service about 1.3 million nephrons in each kidney.

Figure: Blood Flow in the Kidney

NEPHRONS: THE FUNCTIONAL UNIT Nephrons take a simple filtrate of the blood and modify it into urine. Many changes take place in the different parts of the nephron before urine is created for disposal. The term forming urine will be used hereafter to describe the filtrate as it

is modified into true urine. The principle task of the nephron population is to balance the plasma to homeostatic set points and excrete potential toxins in the urine. They do this by accomplishing three principle functions—filtration, reabsorption, and secretion. They also have additional secondary functions that exert control in three areas: blood pressure (via production of renin), red blood cell production (via the hormone EPO), and calcium absorption (via conversion of calcidiol into calcitriol, the active form of vitamin D). Nephrons are the “functional units” of the kidney; they cleanse the blood and balance the constituents of the circulation. The afferent arterioles form a tuft of high-pressure capillaries about 200 µm in diameter, the glomerulus. The rest of the nephron consists of a continuous sophisticated tubule whose proximal end surrounds the glomerulus in an intimate embrace—this is Bowman’s capsule. The glomerulus and Bowman’s capsule together form the renal corpuscle. As mentioned earlier, these glomerular capillaries filter the blood based on particle size. After passing through the renal corpuscle, the capillaries form a second arteriole, the efferent arteriole. These will next form a capillary network around the more distal portions of the nephron tubule, the peritubular capillaries and vasa recta, before returning to the venous system. As the glomerular filtrate progresses through the nephron, these capillary networks recover most of the solutes and water, and return them to the circulation. Since a capillary bed (the glomerulus) drains into a vessel that in turn forms a second capillary bed, the definition of a portal system is met. This is the only portal system in which an arteriole is found between the first and second capillary beds. (Portal systems also link the hypothalamus to the anterior pituitary, and the blood vessels of the digestive viscera to the liver.)

Figure: Blood Flow in the Nephron The two capillary beds are clearly shown in this figure. The efferent arteriole is the connecting vessel between the glomerulus and the peritubular capillaries and vasa recta.

Cortex In a dissected kidney, it is easy to identify the cortex; it appears lighter in color compared to the rest of the kidney. All of the renal corpuscles as well as both the proximal convoluted tubules (PCTs) and distal convoluted tubules are found here. Some nephrons have a short loop of Henle that does not dip beyond the cortex. These nephrons are called cortical nephrons. About 15 percent of nephrons

have long loops of Henle that extend deep into the medulla and are called juxtamedullary nephrons. Renal Corpuscle As discussed earlier, the renal corpuscle consists of a tuft of capillaries called the glomerulus that is largely surrounded by Bowman’s (glomerular) capsule. The glomerulus is a high-pressure capillary bed between afferent and efferent arterioles. Bowman’s capsule surrounds the glomerulus to form a lumen, and captures and directs this filtrate to the PCT. The outermost part of Bowman’s capsule, the parietal layer, is a simple squamous epithelium. It transitions onto the glomerular capillaries in an intimate embrace to form the visceral layer of the capsule. Here, the cells are not squamous, but uniquely shaped cells (podocytes) extending finger-like arms (pedicels) to cover the glomerular capillaries. These projections interdigitate to form filtration slits, leaving small gaps between the digits to form a sieve. As blood passes through the glomerulus, 10 to 20 percent of the plasma filters between these sieve-like fingers to be captured by Bowman’s capsule and funneled to the PCT. Where the fenestrae (windows) in the glomerular capillaries match the spaces between the podocyte “fingers,” the only thing separating the capillary lumen and the lumen of Bowman’s capsule is their shared basement membrane. These three features comprise what is known as the filtration membrane. This membrane permits very rapid movement of filtrate from capillary to capsule though pores that are only 70 nm in diameter.

Figure: Podocytes Podocytes interdigitate with structures called pedicels and filter substances in a way similar to fenestrations. In (a), the large cell body can be seen at the top right corner, with branches extending from the cell body. The smallest finger-like extensions are the pedicels. Pedicels on one podocyte always interdigitate with the pedicels of another podocyte. (b) This capillary has three podocytes wrapped around it.

Figure: Fenestrated Capillary Fenestrations allow many substances to diffuse from the blood based primarily on size.

The fenestrations prevent filtration of blood cells or large proteins, but allow most other constituents through. These substances cross readily if they are less than 4 nm in size and most pass freely up to 8 nm in size. An additional factor affecting the ability of substances to cross this barrier is their electric charge. The proteins associated with these pores are negatively charged, so they tend to repel negatively charged substances and allow positively charged substances to pass more readily. The basement membrane prevents filtration of medium-to-large proteins such as globulins. There are also mesangial cells in the filtration membrane that can contract to help regulate the rate of filtration of the glomerulus. Overall, filtration is regulated by fenestrations in capillary endothelial cells, podocytes with filtration slits, membrane charge, and the basement membrane between capillary cells. The result is the creation of a filtrate that does not contain cells or large proteins, and has a slight predominance of positively charged substances. Lying

just

outside

Bowman’s

capsule

and

the

glomerulus

is

the juxtaglomerular apparatus (JGA). At the juncture where the afferent and efferent arterioles enter and leave Bowman’s capsule, the initial part of the distal convoluted tubule (DCT) comes into direct contact with the arterioles. The wall of the DCT at that point forms a part of the JGA known as the macula densa. This cluster of cuboidal epithelial cells monitors the fluid composition of fluid flowing through the DCT. In response to the concentration of Na+ in the fluid flowing past them, these cells release paracrine signals. They also have a single, nonmotile cilium that responds to the rate of fluid movement in the tubule. The paracrine signals released in response to changes in flow rate and Na+ concentration are adenosine triphosphate (ATP) and adenosine.

Figure: Juxtaglomerular Apparatus and Glomerulus (a) The JGA allows specialized cells to monitor the composition of the fluid in the DCT and adjust the glomerular filtration rate. (b) This micrograph shows the glomerulus and surrounding structures. LM × 1540. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

A second cell type in this apparatus is the juxtaglomerular cell. This is a modified, smooth muscle cell lining the afferent arteriole that can contract or relax in response to ATP or adenosine released by the macula densa. Such contraction and relaxation regulate blood flow to the glomerulus. If the osmolarity of the filtrate is too high (hyperosmotic), the juxtaglomerular cells will contract, decreasing the glomerular filtration rate (GFR) so less plasma is filtered, leading to less urine formation and greater retention of fluid. This will ultimately decrease blood osmolarity toward the physiologic norm. If the osmolarity of the filtrate is too low, the juxtaglomerular cells will relax, increasing the GFR and enhancing the loss of water to the urine, causing blood osmolarity to rise. In other words, when osmolarity goes up, filtration and urine formation decrease and water is retained. When osmolarity goes down, filtration and urine formation increase and water is

lost by way of the urine. The net result of these opposing actions is to keep the rate of filtration relatively constant. A second function of the macula densa cells is to regulate renin release from the juxtaglomerular cells of the afferent arteriole. Active renin is a protein comprised of 304 amino acids that cleaves several amino acids from angiotensinogen to produce angiotensin I. Angiotensin I is not biologically active until converted to angiotensin II by angiotensin-converting enzyme (ACE) from the lungs. Angiotensin II is a systemic vasoconstrictor that helps to regulate blood pressure by increasing it. Angiotensin II also stimulates the release of the steroid hormone aldosterone from the adrenal cortex. Aldosterone stimulates Na+ reabsorption by the kidney, which also results in water retention and increased blood pressure.

Figure: Conversion of Angiotensin I to Angiotensin II The enzyme renin converts the pro-enzyme angiotensin I; the lung-derived enzyme ACE converts angiotensin I into active angiotensin II.

Proximal Convoluted Tubule (PCT) Filtered fluid collected by Bowman’s capsule enters into the PCT. It is called convoluted due to its tortuous path. Simple cuboidal cells form this tubule with prominent microvilli on the luminal surface, forming a brush border. These microvilli create a large surface area to maximize the absorption and secretion of solutes (Na+, Cl–, glucose, etc.), the most essential function of this portion of the nephron. These cells actively transport ions across their membranes, so they possess a high concentration of mitochondria in order to produce sufficient ATP. Loop of Henle The descending and ascending portions of the loop of Henle (sometimes referred to as the nephron loop) are, of course, just continuations of the same tubule. They run adjacent and parallel to each other after having made a hairpin turn at the deepest point of their descent. The descending loop of Henle consists of an initial short, thick portion and long, thin portion, whereas the ascending loop consists of an initial short, thin portion followed by a long, thick portion. The descending thick portion consists of simple cuboidal epithelium similar to that of the PCT. The descending and ascending thin portions consists of simple squamous epithelium. As you will see later, these are important differences, since different portions of the loop have different permeabilities for solutes and water. The ascending thick portion consists of simple cuboidal epithelium similar to the DCT. Distal Convoluted Tubule (DCT) The DCT, like the PCT, is very tortuous and formed by simple cuboidal epithelium, but it is shorter than the PCT. These cells are not as active as those in the PCT; thus, there are fewer microvilli on the apical surface. However, these

cells must also pump ions against their concentration gradient, so you will find of large numbers of mitochondria, although fewer than in the PCT. Collecting Ducts The collecting ducts are continuous with the nephron but not technically part of it. In fact, each duct collects filtrate from several nephrons for final modification. Collecting ducts merge as they descend deeper in the medulla to form about 30 terminal ducts, which empty at a papilla. They are lined with simple squamous epithelium with receptors for ADH. When stimulated by ADH, these cells will insert aquaporin channel proteins into their membranes, which as their name suggests, allow water to pass from the duct lumen through the cells and into the interstitial spaces to be recovered by the vasa recta. This process allows for the recovery of large amounts of water from the filtrate back into the blood. In the absence of ADH, these channels are not inserted, resulting in the excretion of water in the form of dilute urine. Most, if not all, cells of the body contain aquaporin molecules, whose channels are so small that only water can pass. At least 10 types of aquaporins are known in humans, and six of those are found in the kidney. The function of all aquaporins is to allow the movement of water across the lipid-rich, hydrophobic cell membrane.

URETER The ureters are muscular ducts that propel urine from the kidneys to the urinary bladder. In the human adult, the ureters are usually 25–30 cm (10– 12 in) long. In humans, the ureters arise from the renal pelvis on the medial aspect of each kidney before descending towards the bladder on the front of the psoas major muscle. The ureters cross the pelvic brim near the bifurcation of the iliac

arteries (which they run over). This "pelviureteric junction" is a common site for the impaction of kidney stones (the other being the uteterovesical valve). The ureters run posteriorly on the lateral walls of the pelvis. They then curve anteriormedially to enter the bladder through the back, at the vesicoureteric junction, running within the wall of the bladder for a few centimeters. The backflow of urine is prevented by valves known as ureterovesical valves. In the female, the ureters pass through the mesometrium on the way to the bladder.

URINARY BLADDER The urinary bladder is the organ that collects waste excreted by the kidneys prior to disposal by urination. It is a hollow muscular, and distensible (or elastic) organ, and sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra. Embryologically, the bladder is derived from the urogenital sinus, and it is initially continuous with the allantois. In human males, the base of the bladder lies between the rectum and the pubic symphysis. It is superior to the prostate, and separated from the rectum by the rectovesical excavation. In females, the bladder sits inferior to the uterus and anterior to the vagina. It is separated from the uterus by the vesicouterine excavation. In infants and young children, the urinary bladder is in the abdomen even when empty.

URETHRA In anatomy, the (from Greek – ourethra) is a tube which connects the urinary bladder to the outside of the body. In humans, the urethra has an excretory function in both genders to pass.

SUBSTANCES

BILE After bile is produced in the liver, it is stored in the gall bladder. It is then secreted within the small intestine where it helps to emulsify fats in the same manner as soap. Bile also contains bilirubin, which is a waste product. Bile salts can be considered waste that is useful for the body given that they have a role in fat absorption from the stomach. They are excreted from the liver and along with blood flow they help to form the shape of the liver where they are excreted. For instance, if biliary drainage is impaired than that part of the liver will end up wasting away. Biliary obstruction is typically due to masses blocking the ducts of the system such as tumors. The consequences of this depend on the site of blockage and how long it goes on for. There is inflammation of the ducts due to the irritation from the bile acids and this can cause infections. If rupture of the duct takes place it is very traumatic and even fatal.

URINE Within the kidney, blood first passes through the afferent artery to the capillary formation called a glomerulus and is collected in the Bowman's capsule, which filters the blood from its contents—primarily food and wastes. After the filtration process, the blood then returns to collect the food nutrients it needs, while

the wastes pass into the collecting duct, to the renal pelvis, and to the ureter, and are then secreted out of the body via the urinary bladder.

CLINICAL SIGNIFICANCE KIDNEY STONES Scientifically, masses referred to as a renal calculus or nephrolith, or more commonly, “kidney stones,” are solid masses of crystals that may be a variety of shapes, sizes, and textures, that can reside within one or both of the kidneys. Kidney stones form when the balance is off between the concentration of substances that pass through urine, and the substances that are supposed to dissolve them. When substances are not properly dissolved, they have the ability to build up, and form these kidney stones. These stones are most commonly made up of substances such as calcium, cystine, oxalate, and uric acid, as these are the substances that normally would dissolve within the urine. When they do not dissolve correctly and further build up, they will commonly lodge themselves in the urinary tract and in this case, are usually small enough to pass through urine. In extreme situations, however, these stones may lodge themselves within the tube that connects the kidney and the bladder, called the ureter. In this case, they become very large in size and will most likely cause great pain, bleeding, and possibly even block the flow of urine. These can occur in both men and women, and studies show that around 12% of men and 8% of women in America will develop kidney stones within their lifetime.

Treatment In those extreme situations, in which kidney stones are too large to pass on their own, patients may seek removal. Most of these treatments involving kidney stone removal are done by an urologist; a physician who specializes in the organs of the Urinary system. A common way of removal is shock wave lithotripsy, in which the urologist will shock the kidney stone into smaller pieces via laser, allowing these pieces to further pass through the urine on their own, as a normal case of kidney stones. Larger, more serious cases may demand Cystoscopy, Ureteroscopy, or Percutaneous Nephrolithotomy, in which the doctor will use a viewing tool or camera to locate the stone, and based on the size or situation, may either chose to continue with surgical removal, or use the shock wave lithotripsy treatment. Once the kidney stone(s) are successfully eliminated, the urologist will commonly suggest medication to prevent future recurrences.

PYELONEPHRITIS Pyelonephritis is a type of urinary tract infection that occurs when bacteria enters the body through the urinary tract. It causes an inflammation of the renal parenchyma, calyces, and pelvis. There are three main classifications of pyelonephritis: acute, chronic and xanthogranulomatous.

Acute Pyelonephritis In acute pyelonephritis, the patient experiences high fever, abdominal pain and pain while passing urine. Treatment for acute pyelonephritis is provided via antibiotics and an extensive urological investigation is conducted to find any abnormalities and prevent recurrence.

Pyelonephritis In chronic pyelonephritis, patients experience persistent abdominal and flank pain, high fever, decreased appetite, weight loss, urinary tract symptoms and blood in the urine. Chronic pyelonephritis can also lead to scarring of the renal parenchyma caused by recurrent kidney infections.

Xanthogranulomatous Pyelonephritis Xanthogranulomatous pyelonephritis is an unusual form of chronic pyelonephritis. It results in severe destruction of the kidney and causes granulomatous abscess formation. Patients infected with Xanthogranulomatous pyelonephritis experience recurrent fevers, anemia, kidney stones and loss of function in the affected kidney.

Treatment A urine culture and antibiotics sensitivity test is issued for patients who are believed to have pyelonephritis. Since most cases of pyelonephritis are caused from bacterial infections, antibiotics are a common treatment option. Depending on the species of infecting organism and antibiotics sensitivity profile of the organism, treatment may include fluoroquinolones, cephalosporins, aminoglycosides, or trimethoprim

individually

or

in

combination.

For

patients

with

xanthogranulomatous pyelonephritis, treatment might include antibiotics as well as surgery. Nephrectomy is the most common surgical treatment for a majority of cases involving xanthogranulomatous pyelonephritis.

Epidemiology In men, roughly 2-3 cases per 10,000 are treated as outpatients and 1 in 10,000 cases require admission to the hospital. In women, approximately 12–13 in 10,000 cases are treated as outpatients and 3-4 cases are admitted to a hospital. The most common age group affected by Xanthogranulomatous pyelonephritis is middle-aged women. Infants and elderly are also at an increased risk because of hormonal and anatomical changes.