Renal System

佚名  

T he components of the renal system are the kidneys, ureters, bladder, and urethra. The kidneys, located retroperitoneally in the lumbar area, produce and excrete urine to maintain homeostasis. They regulate the volume, electrolyte concentration, and acid-base balance of body fluids; detoxify the blood and eliminate wastes; regulate blood pressure; and support red blood cell production (erythropoiesis). The ureters are tubes that extend from the kidneys to the bladder; their only function is to transport urine to the bladder. The bladder is a muscular bag that serves as reservoir for urine until it leaves the body through the urethra.

PATHOPHYSIOLOGIC MANIFESTATIONS

Wastes are eliminated from the body by urine formation ― glomerular filtration, tubular reabsorption, and tubular secretion ― and excretion. Glomerular filtration is the process of filtering the blood as it flows through the kidneys. The glomerulus of the renal tubule filters plasma and then reabsorbs the filtrate. Glomerular function depends on the permeability of the capillary walls, vascular pressure, and filtration pressure. The normal glomerular filtration rate (GFR) is about 120 ml/min. To prevent too much fluid from leaving the vascular system, tubular reabsorption opposes capillary filtration. Reabsorption takes place as capillary filtration progresses. When fluid filters through the capillaries, albumin, which doesn't pass through capillary walls, remains behind. As the albumin concentration inside the capillaries increases, the capillaries begin to draw water back in by osmosis. This osmotic force controls the quantities of water and diffusible solutes that enter and leave the capillaries.

Anything that affects filtration or reabsorption affects total filtration effort. Capillary pressure and interstitial fluid colloid osmotic pressure affect filtration. Interstitial fluid pressure and plasma colloid osmotic pressure affect reabsorption.

Altered renal perfusion; renal disease affecting the vessels, glomeruli, or tubules; or obstruction to urine flow can slow the GFR. The results are retention of nitrogenous wastes (azotemia), such as blood urea nitrogen and creatinine, which are consequent to acute renal failure.

Capillary pressure

The renal arteries branch into five segmental arteries, which supply different areas of the kidneys. The segmental arteries then branch into several divisions from which the afferent arterioles and vasa recta arise. Renal veins follow a similar branching pattern ― characterized by stellate vessels and segmental branches ― and empty into the inferior vena cava. The tubular system receives its blood supply from a peritubular capillary network. The ureteral veins follow the arteries and drain into the renal vein. The bladder receives blood through vesical arteries. Vesical veins unite to form the pudendal plexus, which empties into the iliac veins. A rich lymphatic system drains the renal cortex, kidneys, ureters, and bladder.

Capillary pressure reflects mean arterial pressure (MAP). Increased MAP increases capillary pressure, which in turn increases the GFR. When MAP decreases, so do capillary pressure and GFR. Autoregulation of afferent and efferent arterioles minimizes and controls changes in capillary pressure, unless MAP exceeds 180 mm Hg or is less than 80 mm Hg.

Sympathetic branches from the celiac plexus, upper lumbar splanchnic and thoracic nerves, and intermesenteric and superior hypogastric plexuses, which surround the kidneys, innervate the kidneys. Similar numbers of sympathetic and parasympathetic nerves from the renal plexus, superior hypogastric plexus, and intermesenteric plexus innervate the ureters. Nerves that arise from the inferior hypogastric plexus innervate the bladder. The parasympathetic nerve supply to the bladder controls urination.

Increased sympathetic activity and angiotensin II constrict afferent and efferent arterioles, decreasing the capillary pressure. Because these changes affect both the afferent and efferent arterioles, they have no net effect on GFR.

Inadequate renal perfusion accounts for 40% to 80% of acute renal failure. Volume loss (as with GI hemorrhage, burns, diarrhea, and diuretic use), volume sequestration (as in pancreatitis, peritonitis, and rhabdomyolysis), or decreased effective circulating volume (as in cardiogenic shock and sepsis) may reduce circulating blood volume. Decreased cardiac output due to peripheral vasodilatation (by sepsis or drugs) or profound renal vasoconstriction (as in severe cardiac failure, hepatorenal syndrome, or with such drugs as nonsteroidal anti-inflammatories [NSAIDs]) also diminish renal perfusion.

Hypovolemia causes a decrease in MAP that triggers a series of neural and humoral responses: activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, and release of arginine vasopressin. Prostaglandin-mediated relaxation of afferent arterioles and angiotensin II�mediated constriction of efferent arterioles maintain GFR. GRF decreases steeply if MAP decreases to less than 80 mm Hg. Drugs that block prostaglandin production (such as NSAIDs) can cause severe vasoconstriction and acute renal failure during hypotension.

Prolonged renal hypoperfusion causes acute tubular necrosis. Processes involving large renal vessels, microvasculature, glomeruli, or tubular interstitium cause intrinsic renal disease. Emboli or thrombi, aortic dissection, or vasculitis can occlude renal arteries. Cholesterol-rich atheroemboli can occur spontaneously or follow aortic instrumentation. If they lodge in medium and small renal arteries, they trigger an eosinophil-rich inflammatory reaction.

Interstitial fluid colloid osmotic pressure

Few plasma proteins and red blood cells are filtered out of the glomeruli, so interstitial fluid colloid osmotic pressure (the force of albumin in the interstitial fluid) remains low. Large quantities of plasma protein flow through glomerular capillaries. Size and surface charge keep albumin, globulin, and other large proteins from crossing the glomerular wall. Smaller proteins leave the glomerulus but are absorbed by the proximal tubule.

Injury to the glomeruli or peritubular capillaries can increase interstitial fluid colloid osmotic pressure, drawing fluid out of the glomerulus and the peritubular capillaries. Swelling and edema occur in Bowman's space and the interstitial space surrounding the tubule. Increased interstitial fluid pressure opposes glomerular filtration, causes collapse of the surrounding nephrons and peritubular capillaries, and leads to hypoxia and renal cell injury or death. When cells die, intracellular enzymes are released that stimulate immune and inflammatory reactions. This further contributes to swelling and edema.

The resulting increase in interstitial fluid pressure can interfere with glomerular filtration and tubular reabsorption. Loss of glomerular filtration renders the kidney incapable of regulating blood volume and electrolyte composition. Diseases that damage the tubules cause tubular proteinuria because small proteins can move from capillaries into tubules.

Normal glomerular cells, which are endothelial in nature, form a barrier that holds cells and other particles back. The basement membrane typically traps larger proteins. The channels of the basement membrane are coated with glycoproteins that are rich in glutamate, aspartate, and sialic acid. This produces a negative charge barrier that impedes the passage of such anionic molecules as albumin. (See A closer look at the glomerulus ).

Glomerular disease disrupts the basement membrane, allowing large proteins to leak out. Damage to epithelial cells permits albumin leakage. Hypoalbuminemia, as in nephrotic syndrome, is the result of excessive urine loss, increased renal catabolism, and inadequate hepatic synthesis. Plasma oncotic pressure decreases, and edema results as fluid moves from capillaries into the interstitium. Consequent activation of the renin-angiotensin system, AVP, and sympathetic nervous system increases renal salt and water reabsorption, which further contributes to edema. The severity of edema is directly related to the degree of hypoalbuminemia, and is exacerbated by heart disease or peripheral vascular disease.

Plasma colloid pressure

Protein concentration of the plasma determines the plasma colloid pressure (the pulling force of albumin in the intravascular fluid), the major force on reabsorption of fluid into the capillaries. Plasma protein levels can decrease as a result of liver disease, protein loss in the urine, and protein malnutrition.

As oncotic pressure decreases, less fluid moves back into the capillaries and fluid begins to accumulate in the tubular and peritubular areas. Swelling around the tubule causes collapse of the tubule and peritubular capillaries, hypoxia, and death of the nephrons.

Diminished plasma oncotic pressure and urinary protein loss stimulate hepatic lipoprotein synthesis, and the resulting hyperlipedemia manifests as lipid bodies (fatty casts, oval fat bodies) in the urine. Metabolic disturbances result as other proteins are lost in the urine, including thyroxine-binding globulin, cholecalciferol-binding protein, transferrin, and metal-binding proteins. Urine losses of antithrombin III, decreased serum levels of proteins S and C, hyperfibrinogenemia, and enhanced platelet aggregation lead to a hypercoagulable state, as in nephrotic syndrome. Some patients also develop severe immunoglobulin G deficiency, which increases susceptibility to infection.

Structural variations

Variations in normal anatomic structure of the urinary tract occur in 10% to 15% of the total population and range from minor and easily correctable to lethal. Ectopic kidneys, which result if the embryonic kidneys do not ascend from the pelvis to the abdomen, function normally. If the embryonic kidneys fuse as they ascend, the single, U-shaped or horseshoe kidney causes no symptoms in about one third of affected persons. The most common problems associated with horseshoe kidneys include hydronephrosis, infection, and stone formation.

Urinary tract malformations are commonly associated with certain nonrenal anomalies. These characteristics include low-set and malformed ears, chromosomal disorders (especially trisomies 13 and 18), absent abdominal muscles, spinal cord and lower extremity anomalies, imperforate anus or genital deviation, Wilms' tumor, congenital ascites, cystic disease of the liver, and positive family history of renal disease (hereditary nephritis or cystic disease). (See Congenital nephropathies and uropathies .)

Obstruction

Obstruction along the urinary tract causes urine to accumulate behind the source of interference, leading to infection or damage. (See Sources of urinary flow obstruction .) Obstructions may be congenital or acquired. Causes include tumors, stones (calculi), trauma, edema, pregnancy, benign prostatic hyperplasia or carcinoma, inflammation of the GI tract, and loss of ureteral peristaltic activity or bladder muscle function.

Consequences of obstruction depend on the location and whether it is unilateral or bilateral, partial or complete, and acute or chronic, as well as the cause. For example, obstruction of a ureter causes hydroureter, or an accumulation of urine within the ureter, which increases retrograde pressure to the renal pelvis and calyces. As urine accumulates in the renal collection system, hydronephrosis results. If the obstruction is complete and acute in nature, increasing pressure transmitted to the proximal tubule inhibits glomerular filtration. If GFR declines to zero, the result is renal failure.

Chronic partial obstruction compresses structures as urine accumulates and the papilla and medulla infarct. The kidneys initially increase in size, but progressive atrophy follows, with eventual loss of renal mass. The underlying tubular damage decreases the kidney's ability to conserve sodium and water and excrete hydrogen ions and potassium; sodium and bicarbonate are wasted. Urine volume is excessive, even though GFR has declined. The result is an increased risk for dehydration and metabolic acidosis.

Tubular obstruction, caused by renal calculi or scarring from repeated infection, can increase interstitial fluid pressure. As fluid accumulates in the nephron, it backs up into Bowman's capsule and space. If the obstruction is unrelieved, nephrons and capillaries collapse, and renal damage is irreversible. The papillae, which are the final site of urine concentration, are particularly affected.

Relief of the obstruction is usually followed by copious diuresis of sodium and water retained during the period of obstruction, and a return to normal GFR. Excessive loss of sodium and water (more than 10 L/day) is uncommon. If GFR doesn't recover quickly, diuresis may not be significant after relief of the obstruction.

Unresolved obstruction can result in infection or even renal failure. Obstructions below the bladder cause urine to accumulate, forming a medium for bacterial growth.

Cystitis is an infection of the bladder that results in mucosal inflammation and congestion. The detrusor muscle becomes hyperactive, decreasing bladder capacity and leading to reflux into the ureters. This transient reflux can cause acute or chronic pyelonephritis if bacteria ascend to the kidney.

Bilateral obstruction not relieved within 1 week of onset causes acute or chronic renal failure. Chronic renal failure progresses over weeks to months without symptoms until 90% of renal function is lost.

DISORDERS

Renal disorders include acute and chronic renal failure, glomerulonephritis, hypospadias and epispadias, nephrotic syndrome, neurogenic bladder, polycystic kidney, renal agenesis, renal calculi, and vesicoureteral reflux.

Acute renal failure

Acute renal failure, the sudden interruption of renal function, can be caused by obstruction, poor circulation, or underlying kidney disease. Whether prerenal, intrarenal, or postrenal, it usually passes through three distinct phases: oliguric, diuretic, and recovery. About 5% of all hospitalized patients develop acute renal failure. The condition is usually reversible with treatment, but if not treated, it may progress to end-stage renal disease, prerenal azotemia, and death.

Causes

Acute renal failure may be prerenal, intrarenal, or postrenal. Causes of prerenal failure include:

• arrhythmias
• cardiac tamponade
• cardiogenic shock
• heart failure
• myocardial infarction
• burns
• dehydration
• diuretic overuse
• hemorrhage
• hypovolemic shock
• trauma
• antihypertensive drugs
• sepsis
• arterial embolism
• arterial or venous thrombosis
• tumor
• disseminated intravascular coagulation
• eclampsia
• malignant hypertension
• vasculitis.

Causes of intrarenal failure include:

• poorly treated prerenal failure
• nephrotoxins
• obstetric complications
• crush injuries
• myopathy
• transfusion reaction
• acute glomerulonephritis
• acute interstitial nephritis
• acute pyelonephritis
• bilateral renal vein thrombosis
• malignant nephrosclerosis
• papillary necrosis
• polyarteritis nodosa
• renal myeloma
• sickle cell disease
• systemic lupus erythematosus
• vasculitis.

Causes of postrenal failure include:

• bladder obstruction
• ureteral obstruction
• urethral obstruction.

Pathophysiology

The pathophysiology of prerenal, intrarenal, and postrenal failure differ.

Prerenal failure. Prerenal failure ensues when a condition that diminishes blood flow to the kidneys leads to hypoperfusion. Examples include hypovolemia, hypotension, vasoconstriction, or inadequate cardiac output. Azotemia (excess nitrogenous waste products in the blood) develops in 40% to 80% of all cases of acute renal failure.

When renal blood flow is interrupted, so is oxygen delivery. The ensuing hypoxemia and ischemia can rapidly and irreversibly damage the kidney. The tubules are most susceptible to the effects of hypoxemia.

Azotemia is a consequence of renal hypoperfusion. The impaired blood flow results in decreased glomerular filtration rate (GFR) and increased tubular reabsorption of sodium and water. A decrease in GFR causes electrolyte imbalance and metabolic acidosis. Usually, restoring renal blood flow and glomerular filtration reverses azotemia.

Intrarenal failure. Intrarenal failure, also called intrinsic or parenchymal renal failure, results from damage to the filtering structures of the kidneys. Causes of intrarenal failure are classified as nephrotoxic, inflammatory, or ischemic. When the damage is caused by nephrotoxicity or inflammation, the delicate layer under the epithelium (the basement membrane) becomes irreparably damaged, often leading to chronic renal failure. Severe or prolonged lack of blood flow by ischemia may lead to renal damage (ischemic parenchymal injury) and excess nitrogen in the blood (intrinsic renal azotemia).

Acute tubular necrosis, the precursor to intrarenal failure, can result from ischemic damage to renal parenchyma during unrecognized or poorly treated prerenal failure; or from obstetric complications, such as eclampsia, postpartum renal failure, septic abortion, or uterine hemorrhage.

The fluid loss causes hypotension, which leads to ischemia. The ischemic tissue generates toxic oxygen-free radicals, which cause swelling, injury, and necrosis.

Another cause of acute failure is the use of nephrotoxins, including analgesics, anesthetics, heavy metals, radiographic contrast media, organic solvents, and antimicrobials, particularly aminoglycoside antibiotics. These drugs accumulate in the renal cortex, causing renal failure that manifests well after treatment or other toxin exposure. The necrosis caused by nephrotoxins tends to be uniform and limited to the proximal tubules, whereas ischemia necrosis tends to be patchy and distributed along various parts of the nephron.

Postrenal failure. Bilateral obstruction of urine outflow leads to postrenal failure. The cause may be in the bladder, ureters, or urethra.

Bladder obstruction can result from:

• anticholinergic drugs
• autonomic nerve dysfunction
• infection
• tumors.

Ureteral obstructions, which restrict blood flow from kidneys to bladder, can result from:

• blood clots
• calculi
• edema or inflammation
• necrotic renal papillae
• retroperitoneal fibrosis or hemorrhage
• surgery (accidental ligation)
• tumor or uric acid crystals.

Urethral obstruction can be the result of prostatic hyperplasia, tumor, or strictures.

The three types of acute renal failure (prerenal, intrarenal, or postrenal) usually pass through three distinct phases: oliguric, diuretic, and recovery.

Oliguric phase. Oliguria may be the result of one or several factors. Necrosis of the tubules can cause sloughing of cells, cast formations, and ischemic edema. The resulting tubular obstruction causes a retrograde increase in pressure and a decrease in GFR. Renal failure can occur within 24 hours from this effect. Glomerular filtration may remain normal in some cases of renal failure, but tubular reabsorption of filtrate may be accelerated. In this instance, ischemia may increase tubular permeability and cause backleak. Another concept is that intrarenal release of angiotensin II or redistribution of blood flow from the cortex to the medulla may constrict the afferent arterioles, increasing glomerular permeability and decreasing GFR.

Urine output may remain at less than 30 mL/hour or 400 mL/day for a few days to weeks. Before damage occurs, the kidneys respond to decreased blood flow by conserving sodium and water.

Damage impairs the kidney's ability to conserve sodium. Fluid (water) volume excess, azotemia (elevated serum levels of urea, creatinine, and uric acid), and electrolyte imbalance occur. Ischemic or toxic injury leads to the release of mediators and intrarenal vasoconstriction. Medullary hypoxia results in the swelling of tubular and endothelial cells, adherence of neutrophils to capillaries and venules, and inappropriate platelet activation. Increasing ischemia and vasoconstriction further limit perfusion.

Injured cells lose polarity, and the ensuing disruption of tight junctions between the cells promotes backleak of filtrate. Ischemia impairs the function of energy-dependent membrane pumps, and calcium accumulates in the cells. This excess calcium further stimulates vasoconstriction and activates proteases and other enzymes. Untreated prerenal oliguria may lead to acute tubular necrosis.

Diuretic phase. As the kidneys become unable to conserve sodium and water, the diuretic phase, marked by increased urine secretion of more than 400 ml/24 hours, ensues. GFR may be normal or increased, but tubular support mechanisms are abnormal. Excretion of dilute urine causes dehydration and electrolyte imbalances. High blood urea nitrogen (BUN) levels produce osmotic diuresis and consequent deficits of potassium, sodium, and water.

Recovery phase. If the cause of the diuresis is corrected, azotemia gradually disappears and recovery occurs. The diuretic phase may last days or weeks. The recovery phase is a gradual return to normal or near-normal renal function over 3 to 12 months.

Renal failure affects many of the body processes. Metabolic acidosis may be the result of decreased excretion of hydrogen ions. Anemia occurs from erythropoietinemia, glomerular filtration of erythrocytes, or bleeding associated with platelet dysfunction. Sepsis is also common because of decreased white blood cell�mediated immunity. Heart failure can result because of fluid overload and anemia, which cause additional workload to the heart. Anemia also causes tissue hypoxia, which then stimulates increased ventilation and work of breathing. Respiratory compensation for metabolic acidosis has a similar effect on the respiratory system. Abnormalities in quantities or function of anticoagulant proteins, coagulation factor, platelet, or endothelial mediators result in a hypercoagulable state. This results in bleeding or clotting difficulties. Altered mental status and peripheral sensation are believed to be due to effects on the highly sensitive cells of nerves secondary to retained toxins, hypoxia, electrolyte imbalance, and acidosis. The hypermetabolic state induced by this critical illness promotes tissue catabolism.

Signs and symptoms

Signs and symptoms of acute renal failure include:

• oliguria due to decreased GFR
• tachycardia due to hypotension
• hypotension due to hypovolemia
• dry mucous membranes due to stimulation of the sympathetic nervous system
• flat neck veins due to hypovolemia
• lethargy due to altered cerebral perfusion
• cool, clammy skin due to decreased cardiac output and heart failure.

Progressive symptoms include:

• edema related to fluid retention
• confusion due to altered cerebral perfusion and azotemia
• GI symptoms due to altered metabolic status
• crackles on auscultation due to fluid in the lungs
• infection due to altered immune response
• seizures and coma related to alteration in consciousness
• hematuria, petechiae, and ecchymosis related to bleeding abnormalities.

Complications

Complications of acute renal failure may include:

• chronic renal failure
• ischemic parenchymal injury
• intrinsic renal azotemia
• electrolyte imbalance
• metabolic acidosis
• pulmonary edema
• hypertensive crisis
• infection.

Diagnosis

Diagnosis of acute renal failure is based on the following results:

• blood studies showing elevated BUN, serum creatinine, and potassium levels; decreased bicarbonate level, hematocrit, and hemoglobin; and acid pH
• urine studies showing casts, cellular debris, and decreased specific gravity; in glomerular diseases, proteinuria and urine osmolality close to serum osmolality; sodium level less than 20 mEq/L if oliguria results from decreased perfusion, and more than 40 mEq/L if cause is intrarenal
• creatinine clearance test measuring GFR and reflecting the number of remaining functioning nephrons
• electrocardiogram (ECG) showing tall, peaked T waves; widening QRS complex; and disappearing P waves if hyperkalemia is present
• ultrasonography, plain films of the abdomen, kidney-ureter-bladder radiography, excretory urography, renal scan, retrograde pyelography, computed tomographic scans, and nephrotomography.

Treatment

Treatment for acute renal failure includes:

• high-calorie diet that's low in protein, sodium, and potassium to meet meta