chronic renal failure Flashcards
what does kidneys do?
The kidneys have several important functions: They regulate uid volume and the acid/base balance of plasma; excrete nitrogenous waste; synthesize erythro- poietin, 1,25-dihydroxycholecalciferol, and renin; are responsible for drug metabolism; and serve as the target organ for parathormone and aldosterone. Under normal physiologic conditions, 25% of the circulating blood perfuses the kidney each minute. The blood is ltered through a complex series of tubules and glomerular cap- illaries within the nephron, the functional unit of the kidney (Figure 12-1). Ultra ltrate, the precursor of urine, is produced in nephrons at a rate of about 125 mL/min2.
what is renal failure?
Stage 5 is re ected by renal failure, wherein 75% or more of the approximately 2 million nephrons have lost function. With disease pro- gression (stages 2 through 5), nitrogen products accumu- late in the blood, and the kidneys perform fewer excretory, endocrine, and metabolic functions, with eventual loss of the ability to maintain normal homeo- stasis. The resultant clinical syndrome—caused by renal failure, retention of excretory products, and interference with endocrine and metabolic functions—is called uremia. Sequelae involve multiple organ systems, with cardiovascular, hematologic, neuromuscular, endocrine, gastrointestinal, and dermatologic manifestations. The rate of destruction and the severity of disease depend on the underlying causative disorders and contributing factors, with diabetes and hypertension recognized as the primary etiologic diseases.2,6
what are the four most common causes of end stage renal disease?
The four most common known causes of ESRD are diabetes mellitus (37%), hypertension (24%), chronic glomerulonephritis (16%), and polycystic kidney disease (4.5%). Other common causes, in decreasing order, are systemic lupus erythematosus, neoplasm, urologic disease, and acquired immunode ciency syndrome (AIDS) nephropathy.2
what is pathophysiology of renal failure?
Deterioration and destruction of functioning nephrons are the underlying pathologic processes of renal failure. The nephron includes the glomerulus, tubules, and vas- culature. Various diseases affect different segments of the nephron at rst, but the entire nephron eventually is affected. For example, hypertension affects the vascula- ture rst, whereas glomerulonephritis affects the glom- eruli rst. Once lost, nephrons are not replaced. However, because of compensatory hypertrophy of the remaining nephrons, normal renal function is maintained for a time. During this period of relative renal insuf ciency, homeostasis is preserved. The patient remains asymp- tomatic and demonstrates minimal laboratory abnor- malities such as a diminished GFR. Normal function is maintained until greater than 50% of nephrons are destroyed. Subsequently, compensatory mechanisms are overwhelmed, and the signs and symptoms of uremia appear. In terms of morphology, the end-stage kidney is markedly reduced in size, scarred, and nodular2 (Figure
A patient in early renal failure may remain asymptom- atic, but physiologic changes invariably develop as the disease progresses. Such changes result from the loss of nephrons. Renal tubular malfunction causes the sodium pump to lose its effectiveness, and sodium excretion occurs. Along with sodium, excessive amounts of dilute urine are excreted, which accounts for the polyuria that is commonly encountered.2
Patients with advanced renal disease develop uremia, which is uniformly fatal if not treated. Failing kidneys are unable to concentrate and lter the intake of sodium, which contributes to the drop in urine output, develop- ment of uid overload, hypertension, and risk for severe electrolyte disturbances (sodium depletion and hyperkalemia—higher-than-normal levels of potassium) and cardiac disease. These cardiovascular system–related events cause approximately half of the deaths occurring annually among patients with ESRD.2,10
The buildup of nonprotein nitrogen compounds in the blood, mainly urea, as a consequence of loss of glomeru- lar ltration function, is called azotemia. Level of azote- mia is measured as blood urea nitrogen (BUN). Acids also accumulate because of tubular impairment. The combination of waste products serves as a substrate for the development of metabolic acidosis, the major result of which is ammonia retention. In the later stages of renal failure, acidosis causes nausea, anorexia, and fatigue. Patients may hyperventilate to compensate for the metabolic acidosis. With acidosis superimposed on ESRD, adaptive mechanisms already are taxed beyond normal levels, and any increase in demand can lead to serious consequences. For example, sepsis or a febrile illness can result in profound acidosis and may be fatal.2
Patients with ESRD demonstrate several hematologic abnormalities, including anemia, leukocyte and platelet dysfunction, and coagulopathy. Anemia, caused by decreased erythropoietin production by the kidney, inhi- bition of red blood cell production and hemolysis, bleed- ing episodes, and shortened red cell survival, is one of the most familiar manifestations of ESRD. Most of these effects result from unidenti ed toxic substances in uremic plasma and from other factors.2 Host defense is compro- mised by nutritional de ciencies, leukocyte dysfunction, depressed cellular immunity, and hypogammaglobu- linemia. This diminished capacity leads to diminished granulocyte chemotaxis, phagocytosis, and bactericidal activity, making affected persons more susceptible to
infection.9
Hemorrhagic diatheses, characterized by tendency
toward abnormal bleeding and bruising, are common in patients with ESRD and are attributed primarily to abnormal platelet aggregation and adhesiveness, decreased platelet factor 3, and impaired prothrombin consumption. Defective platelet production also may play a role. Platelet factor 3 enhances the conversion of prothrombin to thrombin by activated factor X.9
A variety of bone disorders are seen in ESRD; these are collectively referred to as renal osteodystrophy. Decreased kidney function results in decreased 1,25-dihydroxyvitamin D production, which leads to reduced intestinal absorption of calcium (thereby con- tributing to hypocalcemia). With advanced CKD, renal phosphate excretion drops, and results in increased levels of serum phosphorus. Excess phosphorus causes serum calcium to be deposited in bone (osteoid), leading to a decreased serum calcium level and weak bones. In response to low serum calcium, the parathyroid glands are stimulated to secrete parathormone (PTH). This results in secondary hyperparathyroidism. PTH has three main functions:
• •
•
Inhibiting the tubular reabsorption of phosphorus Stimulating renal production of the vitamin D neces- sary for calcium metabolism
Enhancing vitamin D absorption within the intestine
High levels of PTH are sustained, however, because in ESRD the failing kidney does not synthesize 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D; thus, calcium absorption in the gut is inhib- ited. PTH activates tumor necrosis factor and interleukin-1, which mediate bone remodeling, calcium mobilization from bones, and increased excretion of phosphorus, potentially leading to formation of renal and metastatic calci cations. Levels of broblast growth factor 23 (FGF-23), a key regulator of phosphorus and vitamin D metabolism, also increase and result in inhibition of osteoblast maturation and matrix mine- ralization.12 The progression of osseous changes is as follows: osteomalacia (increased unmineralized bone matrix), followed by osteitis brosa (bone resorption with lytic lesions and marrow brosis) (Figure 12-3), and nally, osteosclerosis of variable degree (enhanced bone density) (Figure 12-4). With renal osteodystrophy in children, bone growth is impaired, along with a ten- dency for spontaneous fractures with slow healing, myopathy, aseptic necrosis of the hip, and extraosseous calci cations.
what is sepsis?
Sepsis is defined as whole body inflammation caused by a severe infection. It can be fatal and is complicated by organ dysfunction (kidneys, liver).
