renal insufficiency: acute or chronic decrease in GFR
renal failure: acute or chronic decrease in GFR, but more advanced state of renal insufficiency
may induce all or some of the abnormalities of uremic syndrome
end-stage renal disease (ESRD): abnormalities can no longer be managed
Metabolic Consequences of Renal Failure
water balance
impaired urinary concentrating ability Þ impaired ability to conserve water Þ water loss (diarrhea, vomiting, sweating) Þ ineffective circulating vol Þ further decline renal funct
impaired ability to dilute urine Þ rise in water intake Þ hyponatremia
Sodium balance
Defect in renal Na conservation Þ decrease Na intake Þ volume depletion
Inability to keep pace with large Na intake
Normal person ingests and excretes 110 mEq/day
Nephron loss Þ GFR reduced by half Þ excretes 55 mEq/day
Results in a (+) Na balance of 55mEq/day Þ ECF expansion Þ surviving nephrons increase Na excretion Þ excretes 110 mEq/day
This new steady state results in persisitent ECF vol expansion and high levels of circulating natriuretic factors
Renal function further declines Þ ECF expansion and natriuretic factors become greater Þ volume overload
Trade-off hypothesis: kidney "trades-off" ECF overload and high natriuretic factor levels in order to maintain a steady state for Na intake and excretion
Hypertension, edema, CHF result
Treatment: reduce Na intake (decreases demand to excrete Na) and/or use a diuretic (stimulates nephron to excrete more Na)
Divalent Ion balance
Reduced GFR Þ decreased Phos excretion Þ accumulation of Phos in ECF
Ca/Phos equilibrium: Ca + Phos Þ CaPhos (salt)
Ý serum Phos shifts equil to the salt which ß serum Ca levels Þ stimulates PTH
PTH: extracts Ca from bone into the serum; promotes tubular excretion of Phos
Trade-off hypothesis: new steady state achieved at expense of bone demineralization and increased PTH levels
Impaired vit D activation Þ decreased absorption of Ca from gut Þ negative Ca balance
Result is renal osteodynstrophy = osteoitis fibrosis cystica (from hyperparathyroidism) + osteomalacia (from inadequate activate vit D) + osteoporosis (from chron metab acidosis)
Treatment: give Phos binders which forms salts in the gut and decreases Phos absorption, then give active vit D
Potassium balance
K secretion decreases Þ serum K level increases Þ hyperkalemia
Aldosterone drives Na/K exchange in distal tubule so must be careful to not use substances which can inhibit aldosterone (ie: renin-ang-aldo inhibitors, catecholamine inhibitors, ACE inhibitors) or volume depletion which limits Na delivery to distal tubule
Acid base balance
Ammonia is major carrier of H+ and 99% of excreted acid is in buffered form
ß renal ammonia production Þ ß net acid excretion Þ metabolic acidosis (ß HCO3-)
treatment: low protein diet (ß acid generation) or give exogenous HCO3- supplement to buffer the retaining acid
Nitrogen balance
In negative nitrogen balance and may be protein malnourished
Clinical Manifestations of the Uremic Syndrome
GI: anorexia, nausea, vomiting Þ wght loss Þ protein malnutrition
Cardiovascular: hypertension (Na retention and ECF expansion) Þ cardiovascular disease (#1 cause of death in these patients)
Hematologic: anemia (ß erythropoietin), proportional to degree of renal insufficiency