"pathophysiology [of chronic renal failure]
chronic renal failure often progresses through four stages.
- reduced renal reserve shows a glomerular filtration rate (gfr) of 35% to 50% of normal;
- renal insufficiency, a gfr of 20% to 35% of normal;
- renal failure, a gfr of 20% to 25% of normal;
- end-stage renal disease, a gfr less than 20% of normal.
"nephron damage is progressive; damaged nephrons can't function and don't recover. the kidneys can maintain relatively normal function until about 75% of the nephrons are nonfunctional. surviving nephrons hypertrophy and increase their rate of filtration, reabsorption, and secretion. compensatory excretion continues as gfr diminishes.
urine may contain abnormal amounts of protein, red blood cells (rbcs) and white blood cells or casts. the major end products of excretion remain essentially normal, and nephron loss becomes significant. as gfr decreases, plasma creatinine levels increase proportionately without regulatory adjustment. as sodium delivery to the nephron increases, less is reabsorbed, and sodium deficits and volume depletion follow. the kidney becomes incapable of concentrating and diluting urine.
if tubular interstitial disease is the cause of chronic renal failure, primary damage to the tubules--the medullary portion of the nephron--precedes failure, as do such problems as renal tubular acidosis, salt wasting, and difficulty diluting and concentrating urine. if vascular or glomerular damage is the primary cause, proteinuria, hematuria, and nephrotic syndrome are more prominent.
changes in acid-base balance affect phosphorus and calcium balance. renal phosphate excretion and 1,25(oh)2 vitamin d3 synthesis are diminished. hypocalcemia results in secondary hypoparathyroidism, diminished gfr, and progressive hyperphosphatemia, hypocalcemia, and dissolution of bone. in early renal insufficiency, acid excretion and phosphate reabsorption increase to maintain normal ph. when gfr decreases by 30% to 40%, progressive metabolic acidosis ensues and tubular secretion of potassium increases. total-body potassium levels may increase to life-threatening levels requiring dialysis.
in glomerulosclerosis, distortion of filtration slits and erosion of the glomerular epithelial cells lead to increased fluid transport across the glomerular wall. large proteins traverse the slits but become trapped in glomerular basement membranes, obstructing the glomerular capillaries. epithelial and endothelial injury causes poteinuria. mesangial-cell proliferation, increased production of extracellular matrix, and intraglomerular coagulation cause the sclerosis.
tubulointerstitial injury occurs from toxic or ischemic tubular damage, as with acute tubular necrosis. debris and calcium deposits obstruct the tubules. the resulting defective tubular transport is associated with interstitial edema, leukocyte infiltration, and tubular necrosis. vascular injury causes diffuse or focal ischemia of renal parenchyma, associated with thickening, fibrosis, or focal lesions of renal blood vessels. decreased blood flow then leads to tubular atrophy, interstitial fibrosis, and functional disruption of glomerular filtration, medullary gradients, and concentration.
the structural changes trigger an inflammatory response. fibrin deposits begin to form around the interstitium. microaneurysms result from vascular wall damage and increased pressure secondary to obstruction or hypertension. eventual loss of the nephron triggers compensatory hyperfunction of uninjured nephrons, which initiates a positive-feedback loop of increasing vulnerability.
eventually, the healthy glomeruli are so overburdened that they become sclerotic, stiff, and necrotic. toxins accumulate and potentially fatal changes ensure in all major organ systems.
physiologic changes affect more than one system, and the presence and severity of manifestations depend on the duration of renal failure and its response to treatment. in some fluid and electrolyte imbalances, the kidneys can't retain salt, and hyponatremia results. dry mouth, fatigue, nausea, hypotension, loss of skin turgor, and listlessness can progress to somnolence and confusion later, as the number of functioning nephrons decreases, so does the capacity to excrete sodium and potassium. sodium retention leads to fluid overload and edema; the potassium overload leads to muscle irritability and weakness as well as life-threatening cardiac arrhythmias.
as the cardiovascular system becomes involved, hypertension occurs, and irregular distant heart sounds may be auscultated if pericardial effusion occurs. bibasilar crackles in the lungs and peripheral edema reflect heart failure.
pulmonary changes include reduced macrophage activity and increasing susceptibility to infection. decreased breath sounds in areas of consolidation reflect the presence of pneumonia. as the pleurae become more involved, the patient may experience pleuritic pain and friction rubs.
kussmaul's respirations may be noted as a result of metabolic acidosis. the gi mucosa becomes inflamed and ulcerated, and gums may also be ulcerated and bleeding. stomatitis, uremic fetor (an ammonia smell to the breath), hiccups, peptic ulcer, and pancreatitis in end-stage renal failure are believed to be due to retention of metabolic acids and other metabolic waste products. malnutrition may be secondary to anorexia, malaise, and reduced dietary intake of protein. the reduced protein intake also affects capillary fragility and results in decreased immune functioning and poor wound healing.
normochromic normocytic anemia and platelet disorders with prolonged bleeding time ensue as diminished erythropietin secretion leads to reduced rbc production in the bone marrow. uremic toxins associated with chronic renal failure shorten rbc survival time. the patient experiences lethargy and dizziness.
demineralization of the bone (renal osteodystrophy) manifested by bone pain and pathologic fractures is due to decreased renal activation of vitamin d (which decreases absorption of dietary calcium), retention of phosphate (which increases urinary loss of calcium), and increased circulation of parathyroid hormone (which is caused by decreased urinary excretion).
the skin acquires a grayish yellow tint as urine pigments (urichromes) accumulate. inflammatory mediators released by retained toxins in the skin cause pruritis. uric acid and other substances in the sweat crystallize and accumulate on the skin as uremic frost. high plasma calcium levels are also associated with pruritis.
restless leg syndrome (abnormal sensation and spontaneous movement of the feet and lower legs), muscle weakness, and decreased deep tendon reflexes are believed to result from the effect of toxins on the nervous system.
clinical alert restless leg syndrome is one of the first signs of peripheral neuropathy. this condition will eventually progress to paresthesia and motor nerve dysfunction (bilateral footdrop) unless dialysis is initiated.
chronic renal failure increases the risk of death from infection. this is related to suppression of cell-mediated immunity and a reduction in the number and function of lymphocytes and phagocytes.
all hormone levels are impaired in excretion and activation. females may be anovulatory, amenorrheic, or unable to carry pregnancy to full term. males tend to have decreased sperm counts and impotence."