Chapter II - Urinary System

Kidneys

The kidneys are bean-shaped excretory organs in vertebrates. Part of the urinary system, the kidneys filter wastes (especially urea) from the blood and excrete them, along with water, as urine. The medical field that studies the kidneys and diseases affecting the kidney is called nephrology.

Location
In humans, the kidneys are located in the posterior part of the abdomen. There is one on each side of the spine; the right kidney sits just below the liver, the left below the spleen. Above each kidney is an adrenal gland (also called the suprarenal gland).

Fig: Human kidneys viewed from behind with spine removed (will be added later)

The kidneys are retroperitoneal, which means they lie behind the peritoneum, the lining of the abdominal cavity. They are approximately at the vertebral level T12 to L3, and the right kidney usually lies slightly lower than the left in order to accommodate the liver.

Organization
The upper parts of the kidneys are partially protected by the eleventh and twelfth ribs, and each whole kidney is surrounded by two layers of fat (the perirenal fat and the pararenal fat) which help to cushion it.

In a normal human adult, each kidney is about 11 cm long and about 5 cm thick, weighing 150 grams. The kidneys are "bean-shaped" organs, and have a concave side facing inwards (medially). On this medial aspect of each kidney is an opening, called the hilum, which admits the renal artery, the renal vein, nerves, and the ureter.

The outermost portion of the kidney is called the renal cortex, which sits directly beneath the kidney's loose connective tissue capsule. Deep to the cortex lies the renal medulla, which is divided into 10-20 renal pyramids in humans. Each pyramid together with the associated overlying cortex forms a renal lobe. The tip of each pyramid (called a papilla) empties into a calyx, which empties into the renal pelvis. The pelvis transmits urine to the urinary bladder via the ureter.

Fig: Above each human kidney is one of the two adrenal glands. (will be added later)

Nephron
The basic functional unit of the kidney is the nephron, of which there are more than a million in each normal adult human kidney. Nephrons regulate water and soluble matter (especially electrolytes) in the body by first filtering the blood, then reabsorbing some necessary fluid and molecules while secreting other, unneeded molecules. Reabsorption and secretion are accomplished with both cotransport and countertransport mechanisms established in the nephrons and associated collecting ducts.

Collecting duct system
Fluid flows from the nephron into the collecting duct system. This segment of the nephron is crucial to the process of water conservation by the organism. In the presence of antidiuretic hormone (ADH; also called vasopressin), these ducts become permeable to water and facilitate its reabsorption, thus concentrating the urine and reducing its volume. Failure of the organism to produce ADH (or inability of the collecting ducts to respond to it) may cause excessive urination, called diabetes insipidus. Conversely, when the organism must eliminate excess water, such as after excess fluid drinking, the production of ADH is decreased and the collecting tubule becomes less permeable to water, rendering urine dilute and abundant. Failure of the organism to decrease ADH production appropriately may lead to water retention and dangerous dilution of body fluids, which in turn may cause severe neurological damage. After being processed along the collecting tubules and ducts, the fluid, now called urine, is drained into the bladder via the ureter, to be finally excluded from the organism.

Functions

• Excretion of waste products-The kidneys excrete a variety of waste products produced by metabolism, for example, urea (from protein catabolism) and uric acid (from nucleic acid metabolism).
• Homeostasis-The kidneys regulate the pH, mineral ion concentration, and water composition of the blood. By exchanging hydronium ions and hydroxyl ions, the blood plasma is maintained by the kidney at pH 7.4. Urine, on the other hand, becomes either acidic at pH 5 or alkaline at pH 8.
• Hormone secretion-The kidneys secrete a variety of hormones, including erythropoietin, renin, and vitamin D.

Terms

• Renal capsule: The membranous covering of the kidney.
• Cortex: The outer layer over the internal medulla. It contains blood vessels, glomeruli (which are the kidneys' "filters") and urine tubes and is supported by a fibrous matrix.
• Hilus: The opening in the middle of the concave medial border for nerves and blood vessels to pass into the renal sinus.
• Renal column: The structures, which support the cortex. They consist of lines of blood vessels and urinary tubes and a fibrous material.
• Renal sinus: The cavity, which houses the renal pyramids.
• Calyces: The recesses in the internal medulla, which hold the pyramids. They are used to subdivide the sections of the kidney. (singular-calyx)
• Papillae: The small conical projections along the wall of the renal sinus. They have openings through which urine passes into the calyces. (singular-papilla)
• Renal pyramids: The conical segments within the internal medulla. They contain the secreting apparatus and tubules and are also called Malpighian pyramids.
• Renal artery: Two renal arteries come from the aorta, each connecting to a kidney. The artery divides into five branches, each of which leads to a ball of capillaries. The arteries supply (unfiltered) blood to the kidneys. The left kidney receives about 60% of the renal blood flow.
• Renal vein: The filtered blood returns to circulation through the renal veins, which join into the inferior vena cava.
• Renal pelvis: Basically just a funnel, the renal pelvis accepts the urine and channels it out of the hilus into the ureter.
• Ureter: A narrow tube 40 cm long and 4 mm in diameter. Passing from the renal pelvis out of the hilus and down to the bladder. The ureter carries urine from the kidneys to the bladder by means of peristalsis.
• Medical terms related to the kidneys involve the prefixes renal- and nephro-.
• Nephrectomy-Surgical removal of the kidney is a nephrectomy, while a radical nephrectomy is removal of the kidney, its surrounding tissue, lymph nodes, and potentially the adrenal gland. A radical nephrectomy is performed for removal of cancers.

Diseases and disorders

Congenital

• Polycystic kidney disease(PKD)-is a progressive, genetic disorder of the kidneys. PKD is characterized by the presence of multiple cysts (polycystic) in both kidneys. The disease can also damage the liver, pancreas and rarely the heart and brain.
  - Autosomal dominant polycystic kidney disease (ADPKD) is generally a late onset disorder characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. Kidney manifestations in this disorder include renal function abnormalities, hypertension, renal pain, and renal insufficiency.
  - Autosomal recessive polycystic kidney disease (ARPKD) is much rarer that ADPKD and is often lethal. The signs and symptoms of the condition are usually apparent at birth or in early infancy.
• Congenital hydronephrosis
• Renal dysplasia
• Congenital obstruction of urinary tract
• Horseshoe kidney- Horseshoe kidney is a congenital disorder, affecting about 1 in 500 children, in which a person's two kidneys fuse together to form a horseshoe-shape. This is the most common type of fusion anomaly in the kidneys.
• Duplicated ureter

Acquired

• Renal failure-Acute renal failure & chronic renal failure
• Kidney stones are a relatively common and particularly painful disorder.
• Pyelonephritis is infection of the kidneys and is frequently caused by complication of a urinary tract infection.
• Azotemia is a toxic condition characterized by abnormal and dangerously high levels of urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood.
• Hydronephrosis is the enlargement of one or both of the kidneys caused by obstruction of the flow of urine.
• In nephrotic syndrome, the glomerulus has been damaged so that a large amount of protein in the blood enters the urine. Other frequent features of the nephrotic syndrome include swelling, low serum albumin, and high cholesterol.
• Kidney tumors 1) Wilms tumor 2) Renal cell carcinoma
• Glomerulonephritis-Glomerulonephritis is a primary or secondary autoimmune renal disease featuring inflammation of the glomeruli. It may be asymptomatic, or present with hematuria and/or proteinuria (blood resp. protein in the urine). There are many recognized types, divided in acute, subacute or chronic glomerulonephritis. Causes are infectious (bacterial, viral or parasitic pathogens), autoimmune or paraneoplastic.
• Diabetic nephropathy- Diabetic nephropathy, also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries.
• Lupus nephritis- Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus (SLE), a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints and nervous system.
• Minimal change disease- Minimal change disease or nil disease (lipoid nephrosis) is a disease of the kidney which causes nephrotic syndrome and usually affects children (peak incidence at 2-3 years of age).
• Trauma
• Interstitial nephritis- Interstitial nephritis (or Tubulo-interstitial nephritis) is a form of nephritis affecting the interstititum of the kidneys surrounding the tubules.
• Common causes include infection, or reaction to medication (such as an analgesic or antibiotics.)

Renal failure
Renal failure is the condition where the kidneys fail to function properly. Physiologically, renal failure is described as a decrease in the glomerular filtration rate. Clinically, this manifests in an elevated serum creatinine. It can broadly be divided into two categories: acute renal failure and chronic renal failure.

Chronic renal failure (CRF) develops slowly and gives few symptoms initially. It can be the complication of a large number of kidney diseases, such as IgA nephritis, glomerulonephritis, chronic pyelonephritis and urinary retention. End-stage renal failure (ESRF) is the ultimate consequence, in which case dialysis is generally required while a donor for renal transplant is found.

Acute renal failure (ARF) is, as the name implies, a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 to 500 mL/day in adults, less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants), body water and body fluids disturbances and electrolyte derangement. An underlying cause must be identified to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these underlying causes.

Wilms' tumor

Wilms tumor is a neoplasm of the kidneys that typically occurs in children. It is eponymously named after Dr Max Wilms, a German surgeon (1867-1918). It is also known as a nephroblastoma.

Approximately 500 cases are diagnosed in the U.S. annually. Majority of them (75%) occur in otherwise normal children; a minority (25%) is associated with other developmental abnormalities. Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, fibrous tissue. The tumor is compressing the normal kidney parenchyma. Wilms tumor may be separated into 2 prognostic groups based on pathologic characteristics:

· Favorable - Contains well developed components mentioned above
· Anaplastic - Contains diffuse anaplasia (poorly developed cells)

Wilms tumor can affect any child regardless of race, sex, country of origin, or parental occupation. The disease is mostly noticed around age three, but has been recorded in children as old as age sixteen. Most cases begin with experience of the following symptoms:

• Abdominal mass
• Blood in the urine
• Fever
• Less frequent anorexia, vomiting, and malaise
• It can be associated with a WAGR complex. This complex includes Wilms' Tumor, aniridia, genitourinary malformation, and mental motor retardation.

Renal Cell Carcinoma

Renal cell carcinoma, also known by the eponym Grawitz tumor, is the most common form of kidney cancer arising from the renal tubule. It is the most common type of kidney cancer in adults. Initial therapy is with surgery. It is notoriously resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy.

Signs and symptoms

The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This "classic triad" is infrequently present when the patient first presents for medical attention.

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion, which disturbs the renal contour. It will frequently have an irregular or lobulated margin. 85% of solid renal masses will be RCC. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat). Following intravenous contrast administration (computed tomography or magnetic resonance imaging), enhancement will be noted, and will increase the conspicuity of the tumor relative to normal renal parenchyma.

Treatment

· If it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with surgery. If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with chemotherapy and other treatments.

· Surgical removal of all or part of the kidney (nephrectomy) is recommended. This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues.

· Percutaneous, image-guided therapies, usually managed by radiologists, are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy).

· Radiation therapy is not commonly used for treatment of renal cell carcinoma because it is usually not successful. Radiation therapy may be used to palliate the symptoms of skeletal metastases.

· Medications such as alpha-interferon and interleukin-2 (IL-2) have been successful in reducing the growth of some renal cell carcinomas, including some with metastasis. IL-2 (Proleukin®) is presently the only therapy FDA-approved for the treatment of metastatic renal cell carcinoma (kidney cancer).