Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

U N I T 7

Neuromuscular Complications Many persons with CKD have alterations in peripheral and central nervous system function. 13,37 Peripheral neu- ropathy, or involvement of the peripheral nerves, affects the lower limbs more frequently than the upper limbs. It is symmetric, affects both sensory and motor func- tion, and is associated with atrophy and demyelination of nerve fibers, possibly due to uremic toxins. Restless leg syndrome is a manifestation of peripheral nerve involvement and can be seen in as many as two thirds of persons on dialysis. This syndrome is characterized by creeping, prickling, and itching sensations that typically are more intense at rest. Temporary relief is obtained by moving the legs. A burning sensation of the feet, which may be followed by muscle weakness and atrophy, is a manifestation of uremia. The central nervous system disturbances in uremia are similar to those caused by other metabolic and toxic disorders. Sometimes referred to as uremic encepha- lopathy, the condition is poorly understood and may result, at least in part, from an excess of toxic organic acids that alter neural function. Electrolyte abnormali- ties, such as sodium shifts, also may contribute. The manifestations are more closely related to the progress of the uremic state than to the level of the metabolic end products. Reductions in alertness and awareness are the earliest and most significant indications of uremic encephalopathy. These often are followed by an inabil- ity to fix attention, loss of recent memory, and percep- tual errors in identifying persons and objects. Delirium and coma occur late in the disease course; seizures are the preterminal event. Disorders of motor function commonly accompany the neurologic manifestations of uremic encephalopa- thy. During the early stages, there often is difficulty in performing fine movements of the extremities; the gait becomes unsteady and clumsy with tremulousness of movement. Asterixis (dorsiflexion movements of the hands and feet) typically occurs as the disease pro- gresses. It can be elicited by having the person hyper- extend his or her arms at the elbow and wrist with the fingers spread apart. If asterixis is present, this position causes side-to-side flapping movements of the fingers. Sexual Dysfunction Alterations in sexual function and reproductive ability are common in CKD. 38 The cause probably is multifac- torial and may result from high levels of uremic toxins, neuropathy, altered endocrine function, psychological factors, and medications (e.g., antihypertensive drugs). Impotence occurs in as many as 56% of male patients on dialysis. Derangements of the pituitary and gonadal hormones, such as decreases in testosterone levels and increases in prolactin and luteinizing hormone levels, are common and cause erectile difficulties and decreased spermatocyte counts. Loss of libido may result from chronic anemia and decreased testosterone levels. Impaired sexual function in women is manifested by abnormal levels of progesterone, luteinizing hormone, and prolactin. Hypofertility, menstrual abnormalities,

When untreated, anemia causes or contributes to the weakness, fatigue, depression, insomnia, and decreased cognitive function that commonly accom- pany CKD. There also is an increasing concern regard- ing the physiologic effects of anemia on cardiovascular function. 32 The anemia of renal failure produces a decrease in blood viscosity and a compensatory increase in heart rate. The decreased blood viscosity also exacerbates peripheral vasodilation and contrib- utes to decreased vascular resistance. Cardiac output increases in a compensatory fashion to maintain tis- sue perfusion. Anemia also limits myocardial oxygen supply, particularly in persons with coronary heart disease, predisposing to angina pectoris and other ischemic events. A remarkable advance in the treatment of anemia in CKDwas realized when recombinant human erythropoi- etin (rhEPO) became available. Because iron deficiency is common among persons with CKD, iron supplemen- tation often is needed. 33 Iron can be given orally or intravenously. Intravenous iron is used for treatment of persons who are not able to maintain adequate iron status with oral iron. Although adverse reactions have been reported, intravenous preparations are generally safe and well tolerated. Coagulation Disorders. The coagulation disorders of CKD are mainly caused by platelet dysfunction. 35 Platelet counts may be slightly decreased and the bleed- ing time is prolonged because of abnormal adhesive- ness and aggregation. Clinically, persons with CKD can experience epistaxis (nosebleeds), menorrhagia (excessive menstrual bleeding), gastrointestinal bleed- ing, and bruising of the skin and subcutaneous tissues. Coagulative function improves with dialysis but does not completely normalize, suggesting that uremia con- tributes to the problem. Persons with CKD also have greater susceptibility to thrombotic disorders, particu- larly if their underlying disease was characterized by a nephrotic presentation. Immunologic Disorders All aspects of inflammation and immune function may be affected adversely by the high levels of urea and metabolic wastes seen in CKD. A decreased granu- locyte count, defective phagocyte function, impaired acute inflammatory response, and impaired humoral and cell-mediated immunity are typical. These immu- nologic abnormalities decrease the efficiency of the immune response to infection, which is a common complication of CKD. 36 Skin and mucosal barriers to infection also may be defective. In persons who are maintained on dialysis, vascular access devices are common portals of entry for pathogens. Many persons with CKD fail to mount a fever with infection, making a diagnosis of infection more difficult. The delayed-type hypersensitivity response is also impaired. Although persons with CKD have normal humoral responses to vaccines, a more aggressive immunization program may be needed.