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
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
Neurologic (CNS
): uremia Þ encephalopathy (ß mental function)
Neurologic (PNS
): ascending symmetric peripheral neuropathy Þ numbness and dysesthesias (restless leg syndrome)
Endocrine
: azotemic pseudo-diabetes
Treatment of end-stage renal disease (ESRD)
Hemodialysis
85% of patients
diffusive clearance
semipermeable memb: K, urea, phos go from blood to dialysate; HCO3-, Ca++ from dialysate to blood
ultrafiltration (hydraulic pressure gradient)
water goes from blood to dialysate
Peritoneal dialysis
15%
fill peritoneal cavity with peritoneal dialysate
Þ similar results
need four exchanges per day
Renal Transplantation
Restores all kidney functions
Requires lifetime immosuppressive therapy
Þ more prone to infections
Lasts 10-12 years
12,000 – 13,000 transplants per year (250,000 dialysis patients)