Important Pathophysiologic Manifestations of Chronic Renal Failure

Hypervolemia

Total-body contents of Na⁺ and H₂ O are increased, ^[5] although this increase may not be clinically apparent until the GFR is reduced to very low levels. Weight gain is usually associated with volume expansion and is offset by the concomitant loss of lean body mass. The combination of loop diuretics with metolazone, which acts by inhibiting the Na-Cl cotransporter of the distal convoluted tubule, can overcome diuretic resistance.

Acidemia

Although urine can be acidified normally in most patients with CRF, these patients have a reduced ability to produce ammonia. In the early stages, the accompanying organic anions are excreted in urine, and the metabolic acidosis is of the non-anion gap variety. However, with advanced renal failure, a fairly large "anion gap" may develop (to approximately 20 mmol/L) with a reciprocal fall in plasma HCO₃ ^- concentration. This acidemia is

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Hyperkalemia

The approximate daily filtered load of K⁺ is 700 mmol. Most of this filtered load is reabsorbed in tubule segments, and most of the K⁺ excreted in the final urine reflects events governing K⁺ handling at the level of the cortical collecting tubule and beyond. K⁺ excretion in the gastrointestinal tract is augmented in patients with CRF. However, hyperkalemia may be precipitated in a number of clinical situations, including protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, metabolic acidosis, and exposure to a variety of medications that inhibit K⁺ entry into cells or K⁺ secretion in the distal nephron.

Cardiac and Pulmonary Manifestations

Hypertension is a common complication of CRF and ESRD. Because hypervolemia is the major cause of hypertension in uremia, normotension is usually restored by the use of diuretics in predialysis patients or by dialysis in ESRD patients. Despite therapy, patients continued to be hypertensive because of the vasodilators required for the management of overwhelming hyperreninemia. Patients generally have left ventricular hypertrophy and accelerated atherosclerosis (disordered glucose and fat metabolism).

Pericarditis is usually observed more in underdialyzed patients than in patients with CRF who undergo regular dialysis or in whom dialysis has not been initiated. This pericarditis rarely leads to tamponade.^[14] Pericardiocentesis is

TABLE 54-4 -- Metabolic acidosis in chronic renal failure

	PaCO2 (mm Hg)	pH	HCO3 - (mEq/L)	K+ (mEq/L)
Preoperative	32	7.32	17	5.0
Intraoperative	40	7.25	18	5.3
Postoperative	44	7.21	19	5.6
	48	7.18	19	5.9
The patient is a 36-year-old man with severe diabetic nephropathy and end-stage renal failure undergoing cadaveric renal transplantation. Preoperatively, the patient has a chronic metabolic acidosis (HCO3 - , 17 mEq/L) with partial respiratory compensation (PaCO2 , 32 mm Hg; pH 7.32). Potassium is high normal at 5.0 mEq/L. Intraoperatively, he is given "standard" mechanical minute ventilation, and with "normal" PaCO2 (40 mm Hg), the metabolic acidosis is unmasked (pH 7.25) and potassium climbs to 5.3 mEq/L. His trachea is extubated at the end of the procedure, but graft function is sluggish and the metabolic acidosis remains unchanged. With residual opioid-induced narcosis, moderate CO2 retention occurs (PaCO2 , 44, 48 mm Hg), pH falls further to 7.18, and a dangerous degree of hyperkalemia develops (5.9 mEq/L).
HCO3 - , calculated bicarbonate; K+ , serum potassium; PaCO2 , arterial CO2 tension.

usually avoided because of the risk of hemorrhage with uremic coagulopathy.^[15] These manifestations are relieved by dialysis.

A unique form of pulmonary congestion and edema may occur even in the absence of volume overload and is associated with normal or mildly elevated intracardiac and pulmonary capillary wedge pressure. This entity, characterized radiologically by peripheral vascular congestion giving rise to a "butterfly wing" distribution, is due to increased permeability of alveolar capillary membranes. This "low-pressure" pulmonary edema, as well as the cardiopulmonary abnormalities associated with circulatory overload, usually responds promptly to vigorous dialysis. ^[16]

Hematologic Manifestations

CRF usually causes a normochromic, normocytic anemia. Anemia is generally observed when the GFR falls below 30 mL/min and is due to insufficient production of erythropoietin by the diseased kidneys. Other factors are iron deficiency, either related to or independent of blood loss from repeated laboratory testing, blood retention in the dialyzer, or gastrointestinal bleeding.^[17]

Treatment of anemia with human recombinant erythropoietin (50 to 75 IU/kg subcutaneously triweekly) normalizes the hematocrit, avoids repetitive red cell transfusion, reduces the requirement for hospitalization, and decreases cardiovascular mortality by about 30%.^[18]

Prolongation of the bleeding time because of decreased activity of platelet factor 3, abnormal platelet aggregation and adhesiveness, and impaired prothrombin consumption contribute to the clotting defects. The abnormality in platelet factor 3 correlates can be corrected by dialysis. Prolongation of the bleeding time is seen even in well-dialyzed patients. Abnormal bleeding times and coagulopathy in patients with renal failure may be managed with desmopressin, cryoprecipitate, conjugated estrogens, and blood transfusions, as well as by the use of erythropoietin. ^{[17] [19]}