The Urinary System

4.3a The physiology of the urinary system

The urinary system consists of the kidneys, the ureters, the bladder and the urethra. An alternative name is the renal system, although strictly speaking, renal (from the Latin term for kidney) is a term that refers to the kidneys alone. The Greek word for kidney is nephron, and hence the study of the kidneys is called nephrology.

The fluid that leaves the nephron to enter the collecting tubule and thence the renal pelvis has the composition of urine. This yellow-colored fluid consists mostly (96 percent) of water, with a further 2 percent being urea (the waste product of protein metabolism) and the remaining 2 percent comprising a range of other salts including sodium, potassium and uric acid. In a healthy adult, approximately 1–1.5 liters of urine are passed a day, although this can vary from as little as 500 milliliters to as high as 3 liters, depending on the balance of fluid intake and other fluid losses.

Diuretic drugs that act on the kidney tend to inhibit the amount of water that is reabsorbed, and so increase the volume of urine entering the renal pelvis. Some diuretic drugs may also affect the reabsorption of salts. This is why some diuretics can lead to sodium or potassium depletion, and others may cause a buildup of uric acid (predisposing to an attack of gout).

The kidneys and the formation of red blood cells

Erythropoietin (EPO) is a hormone that is made within the kidneys and is released into the bloodstream in response to low levels of oxygen. It is an essential factor in the production of red blood cells from the bone marrow. When blood oxygen levels drop, the secretion of EPO is stimulated, and this in turn increases the production of red blood cells from the bone marrow. These blood cells are then available to carry more oxygen, and thereby to increase the level of oxygen in the blood.

The kidneys and the control of blood pressure

Healthy kidneys are essential for the control of blood pressure, and disease of the kidneys is one of the causes of hypertension. In addition, the kidneys act in a situation of shock (low blood pressure) to conserve fluid, and so to prevent its loss into the urine. There are at least two important hormone systems that cause the kidney to excrete more fluid when the blood pressure is high and to conserve fluid when the blood pressure drops.

The hormones involved in the kidneys’ control of blood pressure include aldosterone, renin, angiotensin I and II, and atrial natriuretic factor (ANF). ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers are drugs used in the treatment of hypertension and heart failure. They act by blocking the formation of one of these hormones (angiotensin II).

The kidneys and vitamin D metabolism

Although vitamin D is mostly manufactured as a response to the action of sunlight on the skin, it requires conversion within the kidneys to become active in the body. For this reason, kidney disease can be a cause of the disease of weakening of the bones known as osteomalacia.

The physiology of the ureters

The ureters receive a steady flow of urine from the renal pelvis at a rate of 20–100 milliliters/hour. These structures run down the back of the abdominal cavity and enter the bladder where it sits within the pelvis. The flow of urine is aided by waves of muscular contractions that are generated by the smooth muscle fibers within the ureter walls.

The urine that enters the bladder passes through a narrowing, akin to a valve, as it enters the bladder. This important structure prevents the return of urine back into the ureter (known as reflux) from the bladder. The urine enters the bladder in little spurts, which occur every 10 seconds or so.

Figure 4.3a-V The pelvic organs associated with the bladder in the female

Figure 4.3a-VI The pelvic organs associated with the bladder in the male

The bladder is a hollow, pear-shaped organ, the function of which is to act as a reservoir for urine. Figures 4.3a-V and 4.3a-VI above show a vertical section through the pelvis of a woman and a man, respectively. These diagrams illustrate the position of the bladder within the pelvis. Note how in the woman the bladder sits just in front of the cervix and womb. In the man the prostate gland sits at the neck of the bladder, surrounding the first part of the urethra.

The bladder is lined by a form of epithelium called transitional epithelium that has the ability to stretch. Within the wall of the bladder are sheets of smooth muscle, which together are called the detrusor muscle. When the detrusor muscle contracts, it forces urine out through the urethra.

In a healthy adult the desire to urinate arises when the bladder contains more than 300 milliliters of urine. At this stage, the stretch of the bladder muscle stimulates nerve impulses so that the bladder contracts spontaneously (this is a spinal reflex). Indeed, this is what occurs both in the newborn and in someone who has had a spinal injury. However, in the healthy adult, although the sensation of a desire to urinate occurs at this stage, the brain exerts an inhibitory control on this reflex until an appropriate time arises for it to occur. This voluntary control of bladder function is usually learned during the third year of life.

The physiology of the urethra

In both women and men the urethra passes through the region of the body called the perineum that forms the floor of the pelvis. In doing so, it passes through the pelvic floor muscles, which are slung between the pubic bone and the base of the sacrum and coccyx.

At the origin of the urethra is a smooth muscle ring called the internal urethral sphincter. This is generally maintained in a state of contraction, thus holding the urine within the bladder. In addition to the internal sphincter, the muscles of the pelvic floor provide an additional external urethral sphincter as a result of their generally high level of tone. Together, these factors exert a closing pressure on the urethra, which is released when the person intends to urinate.

Diseases of the urinary system are investigated within three distinct conventional specialties. Medical conditions that affect the kidney are treated by a renal physician within the specialty of renal medicine or nephrology. Conditions that affect the ureters, bladder and urethra, and also those conditions of the kidney that may require surgery, are treated by a surgeon called a urologist within the specialty of urology. Conditions that affect the male reproductive organs are also commonly treated by a urologist. However, those conditions that result from sexually transmitted diseases are treated by a genitourinary physician within the specialty of genitourinary medicine or sexual medicine.

The investigation of the urinary system

The investigation of the urinary system involves:

•a thorough physical examination

•urine examination

•blood examination to check for anemia, to assay waste products and salts in the serum, and to look for autoantibodies and other markers of specific diseases

•imaging tests to examine the structure of the urinary system, including ultrasound scan, computed tomography (CT) scan and plain X-ray images

•imaging tests to examine the function of the urinary system, including intravenous urography, cystourethrography and radioactive isotope scans

•examination of the inside of the bladder (cystoscopy)

•biopsy of the kidneys

•urodynamic studies.

These are each considered briefly in turn below.

Physical examination

The urine can also be analyzed for the substances that are dissolved within it. In addition to the usual body wastes, drugs and hormones can also be found in the urine. Therefore, a urine test can detect the presence of illicit drugs or increased levels of hormones. There is very little protein to be found in healthy urine, but in severe kidney disease it may be present in vast quantities. Both the total protein and the albumin (the most common protein in the plasma) levels may be assessed from a urine sample. A 24-hour collection of urine may be used to quantify accurately the protein loss in kidney disease, and can also be used to assess the rate at which blood is filtered by the kidneys (glomerular filtration rate).

Blood examination

A serum sample of blood can be analyzed to reveal the disturbances in blood chemicals that result from kidney failure. In particular, the by-products of protein metabolism (urea and creatinine) may be increased in quantity. In severe kidney disease there may also be disturbances of the concentration of the basic mineral salts, such as sodium, calcium and potassium, in the blood. The level of creatinine may be inserted into a mathematical formula that incorporates the age, ethnicity and sex of the patient to generate an estimate of the amount of fluid filtered by the kidneys in a fixed amount of time. This is the estimated glomerular filtration rate (eGFR), which is a useful indication of the progression of chronic kidney disease (CKD), a condition that becomes increasingly prevalent with aging.

Other factors that indicate a specific cause of kidney disease may also be assayed (e.g. autoantibodies in systemic lupus erythematosus (SLE)). In disease of the prostate gland, a particular protein called prostate-specific antigen (PSA) is assayed, as this is more likely to be raised if cancer is present.

A full blood count (FBC) may reveal the anemia of chronic disease that can accompany chronic kidney disease.

Imaging tests to examine the structure of the urinary system

Ultrasound, magnetic resonance imaging (MRI) and CT scans are used to visualize the shape of the kidneys, ureters and bladder. The images obtained may be used to examine gross defects, such as the presence of cancer or obstruction to the outflow of urine from the bladder, but cannot reveal the more subtle changes that occur in most diseases of the urinary system. An ultrasound scan obtained by means of a probe passed into the anus may also be used to examine the prostate gland.

Figure 4.3b-II Excretion urogram showing a pale patch of contrast in the calyx of the left kidney

The pale patch represents a large calculus (kidney stone).

Cystoscopy

In cystoscopy, a fiber-optic telescope is inserted into the urethra so that the inside of the bladder can be seen directly. The patient is usually heavily sedated, or has a general anesthetic. Biopsies of the bladder can also be taken by means of the cystoscope.

Renal biopsy

Under guidance from an ultrasound scan, a needle may be directed through the skin into the kidney to remove a small sample of tissue for examination. This procedure carries a small but significant risk of bleeding into or around the kidney.

Urodynamic studies

Urodynamics is the study of the pressure of the urine in the bladder and the flow of the stream of the urine from the urethra. Specialized tests to measure the pressure within the bladder and the flow rate are used mostly to investigate the underlying problem in cases of incontinence or obstructed flow of urine. Urodynamic studies may be used in combination with MCU.

4.3c Diseases of the kidneys

The conditions studied in this section are:

Part I: Disease processes that affect the kidney:

•glomerulonephritis – nephritic syndrome and nephrotic syndrome

•acute and chronic pyelonephritis

•kidney and ureteric stones

•polycystic kidney disease

•interstitial nephritis

•hemolytic uremic syndrome

•hypertension and the kidneys

•diabetes and the kidneys

•cancer of the kidney

Part II: Serious consequences of disease of the kidney:

•acute kidney injury (AKI)

•chronic kidney disease (CKD).

All the common diseases of the kidney described in this section may be so severe as to lead to either sudden (acute) or gradual (chronic) failure of the kidney to perform its necessary functions.

Part I: Disease processes that affect the kidney

Glomerulonephritis

Glomerulonephritis is a term used to describe a broad range of conditions that affect the structure of the cup-like origin of the tubules in the kidney and the cluster of blood vessels within this cup known as the glomerulus. In glomerulonephritis the filtering process is impaired. This has the consequence that red blood cells and protein may leak out of the blood into the urine, and also that excess salts, wastes and water may be retained in the circulation.

In medical textbooks, the condition of glomeru-lonephritis may be categorized according to the precise pathological changes occurring in the glomerulus, and these categories are assigned descriptive terms such as minimal change, membranous glomerulonephritis and mesangiocapillary glomerulonephritis. This categorization, which is based on the results of kidney biopsy and is important for predicting prognosis, does not relate directly to the condition that may have caused the disease process. For this reason it is not described further in this section.

Glomerulonephritis can result from a variety of underlying disease processes, but also commonly develops without any obvious cause. In many cases the problem results from the deposition of autoantibodies within the glomerulus. Autoantibodies stimulate the immune response, and the inflammation that results leads to glomerular damage. Autoantibodies may develop as a delayed response to infection, as part of an established autoimmune disease such as systemic lupus erythematosus (SLE) or as a reaction to certain drugs. They may also account for many of the cases of glomerulonephritis of unknown cause.

The Streptococcus bacterium, which is a common cause of sore throat and tonsillitis, used to be a very common cause of antibody-related glomerulonephritis. Post-streptococcal glomerulonephritis tends to lead to a characteristic cluster of symptoms known as nephritic syndrome or acute nephritis (see below). Bright’s disease is an old-fashioned name for nephritic syndrome. This term used to be almost synonymous with post-streptococcal kidney disease.

Other infectious agents that may cause the development of damaging autoantibodies include viruses, such as measles and hepatitis, bacteria, such as Salmonella, and parasites, such as malaria.

Glomerulonephritis may also be part of the disease process of a multisystem autoimmune disease. SLE is the most common specific autoimmune disease known to cause glomerulonephritis. In SLE, chronic kidney disease (CKD) resulting from severe persistent cases of glomerulonephritis is the most common cause of death.

Some drugs may also trigger the development of damaging autoantibodies. The drug that most commonly has this effect is penicillamine, which is prescribed as a disease-modifying treatment in rheumatoid arthritis.

THE CONSEQUENCES OF GLOMERULAR DAMAGE

The effects of glomerulonephritis can be broadly divided into four categories, although in practice, for any individual patient, it may be difficult to assign them to a category. The categories are:

•hematuria (blood in the urine)

•proteinuria (protein in the urine)

•nephritic syndrome (blood and protein in the urine, with high blood pressure and edema)

•nephrotic syndrome (excessive protein in the urine leading to severe edema).

HEMATURIA AND PROTEINURIA IN GLOMERULONEPHRITIS

Some forms of glomerulonephritis cause sufficient damage to the glomerulus to bring about a leakage of red blood cells, protein or both. This leakage may not be sufficiently severe to be visible to the patient, and instead may be picked up on routine urine testing. Greater numbers of red blood cells might cause the urine to appear pink or smoky colored, and excess protein might cause the urine to appear frothy. There may be no other symptoms.

Nevertheless, despite the mildness of the symptoms, the finding of even small amounts of blood or protein in the urine in the absence of urinary infection can be a warning sign of a progressive disease of the kidney. CKD can be the long-term consequence of glomerulonephritis that may be signaled by hematuria or proteinuria. For this reason, all patients who are found to have unexplained hematuria or proteinuria above a certain level will be referred to a renal physician for further investigations.

Some forms of glomerulonephritis that cause hematuria or proteinuria may respond to treatment with immunosuppressant drugs, including corticosteroids. Other immunosuppressant medications that may be prescribed at the same time include azathioprine, cyclophosphamide and chlorambucil. All these drugs can have a wide range of toxic effects.

Nephritic syndrome is a term used to describe a glomerulonephritis that causes severe symptoms to appear rapidly. In nephritic syndrome the patient, commonly a child, becomes unwell with fever, vomiting and pain in the back. There may be a history of a streptococcal infection within the past two to four weeks, although streptococcal infection is not always the cause. The face becomes puffy with edema and blood pressure is raised. The urine may be pink or smoky colored by red blood cells. In severe cases the production of urine becomes severely reduced as the filtration function of the kidney is extremely impaired. The patient is then at risk of death from acute kidney failure or malignant hypertension.

A patient with nephritic syndrome requires close medical observation. In most childhood cases there is full recovery from the condition after four to seven days, although a minority of cases take a more chronic course. In contrast to the forms of glomerulonephritis that cause hematuria and proteinuria alone, most of these chronic cases of nephritic syndrome do not respond to immunosuppressant drugs. In post-streptococcal nephritis a course of penicillin is given to ensure eradication of the Streptococcus.

In acute cases, as the tissue of the kidneys recovers, the toxins and excess salts that have built up in the body are cleared by means of profuse urination. However, in rare cases, the patient may die during the acute illness from acute renal failure and from damage caused to the brain by a rapidly rising blood pressure. Convulsions may develop in these severe cases. This consequence can be prevented with the help of emergency dialysis, which takes over the function of the failing kidney (see later).

In the more chronic cases, and more commonly in adults, there may be persisting damage to the kidneys. This damage can progress to chronic kidney failure over the course of months to years.

NEPHROTIC SYNDROME

Other forms of glomerulonephritis cause the filter of the kidney to leak large amounts of protein. This protein is lost into the urine, which becomes frothy as a result. The main plasma protein to be lost is albumin, but other proteins, including immunoglobulin (the protein that forms the plasma antibodies), are also lost. Nephrotic syndrome describes those cases when excessive amounts of protein are lost into the urine. As albumin is the most abundant plasma protein, this is found in high concentrations in the urine.

Other causes of nephrotic syndrome include the kidney damage that develops in some cases of diabetes, rare drug reactions and allergic reactions.

It is important for the plasma to be maintained at a certain concentration to give it sufficient osmotic pressure to remain in the circulation. The protein albumin plays a vital role in giving the plasma this adequate level of concentration. If albumin is lost, the plasma becomes too dilute, and the plasma fluid tends to move by osmosis into the more concentrated tissue fluid. Excessive fluid collecting in the tissues is called edema. In nephrotic syndrome, the severity of the proteinuria results in severe edema. The patient develops very swollen ankles and legs, and eventually fluid collects in a wide range of body regions, including the abdomen, within the lungs, the facial tissues and the genitalia.

In nephrotic syndrome, changes in the constitution of the plasma mean that clotting becomes a problem, and there is an increased risk of venous thrombosis. Loss of antibodies means that the patient with nephrotic syndrome is more prone to infection. Hyperlipidemia can also develop.

The patient with nephrotic syndrome is treated by means of diuretic medication to encourage loss of the excess tissue fluid, and restriction of salt in the diet. ACE inhibitor medication is prescribed, as this tends to reduce proteinuria, partly by reducing blood pressure. Anticoagulant medication may be given by injection to prevent blood clots. Statins may be prescribed to reduce the hyperlipidemia. Some cases will respond to corticosteroid medication or to other immunosuppressant drugs; this is particularly true in many of the cases that start in childhood.