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Essentials of Diagnosis Produced by atherosclerotic occlusive disease (80–90% of patients) or fibromuscular dysplasia (10–15%). Hypertension. Acute renal failure in patients starting therapy with an ACE inhibitor. General Considerations The two most common forms of renal artery stenosis are atherosclerotic ischemic renal disease and fibromuscular dysplasia. The prevalence of this condition has been estimated only by autopsy and angiographic studies. Approximately 5% of Americans with hypertension suffer from renal artery stenosis. Atherosclerotic ischemic renal disease accounts for nearly all cases of renal artery stenosis. It occurs most commonly in those over 45 years of age with a history of atherosclerotic disease. Other risk factors include renal insufficiency, diabetes mellitus, tobacco use, and hypertension. Clinical Findings SYMPTOMS AND SIGNS Patients with atherosclerotic ischemic renal disease may have refractory hypertension, new-onset hypertension in an older patient, p...

Essentials of Diagnosis Progressive azotemia over months to years. Symptoms and signs of uremia when nearing end-stage disease. Hypertension in the majority. Isosthenuria and broad casts in urinary sediment are common. Bilateral small kidneys on ultrasound are diagnostic. General Considerations Chronic kidney disease affects up to 20 million Americans, or one in nine adults. Most are unaware of the condition because they remain asymptomatic until the disease has significantly progressed. The National Kidney Foundation’s staging system helps clinicians formulate practice plans (Table 22–5). Over 70% of cases of late-stage chronic kidney disease are due to diabetes mellitus or hypertension. Glomerulonephritis, cystic diseases, and other urologic diseases account for another 12%, and 15% of patients have other or unknown causes. Table 22–6. Major causes of chronic renal failure. Glomerulopathies Primary glomerular diseases: Focal and segmental glomerulosclerosis Membran...

Essentials of Diagnosis Hematuria, dysmorphic red cells, red cell casts, and mild proteinuria. Dependent edema and hypertension. Acute renal insufficiency. General Considerations Acute glomerulonephritis is a relatively uncommon cause of acute renal failure, accounting for about 5% of cases of intrinsic renal failure. Pathologically, inflammatory glomerular lesions are seen. These include mesangioproliferative, focal and diffuse proliferative, and crescentic lesions. The larger the percentage of glomeruli involved and the more severe the lesion, the more likely it is that the patient will have a poor clinical outcome. Categorization of acute glomerulonephritis can be done by serologic analysis. Markers include antineutrophil cytoplasmic antibodies (ANCA), anti-GBM antibodies, and other immune markers of disease. Immune complex deposition usually occurs when moderate antigen excess over antibody production occurs. Complexes formed with marked antigen excess tend to remain in the circula...

Essentials of Diagnosis Fever. Transient maculopapular rash. Acute renal insufficiency. Pyuria (including eosinophiluria), white blood cell casts, and hematuria. General Considerations Acute interstitial nephritis accounts for 10–15% of cases of intrinsic renal failure. An interstitial inflammatory response with edema and possible tubular cell damage is the typical pathologic finding. Cell-mediated immune reactions prevail over humoral responses. T lymphocytes can cause direct cytotoxicity or release lymphokines that recruit monocytes and inflammatory cells. Although drugs account for over 70% of cases, acute interstitial nephritis also occurs in infectious diseases, immunologic disorders, or as an idiopathic condition. The most common drugs are penicillins and cephalosporins, sulfonamides and sulfonamide-containing diuretics, NSAIDs, rifampin, phenytoin, and allopurinol. More recently, proton-pump inhibitors have also been recognized as a cause of acute interstitial nephritis. Infec...

Essentials of Diagnosis Acute kidney injury. Clinical scenario consistent with diagnosis (ischemic or toxic insult). Urine sediment with pigmented granular casts and renal tubular epithelial cells is pathognomonic but not essential. General Considerations Acute renal failure due to tubular damage is termed acute tubular necrosis and accounts for 85% of intrinsic acute renal failure. The two major causes of acute tubular necrosis are ischemia and toxin exposure. Ischemia causes tubular damage from states of low perfusion and is often preceded by a state of prerenal azotemia. Ischemic acute renal failure is characterized not only by inadequate GFR but also by renal blood flow inadequate to maintain parenchymal cellular formation. This occurs in the setting of prolonged hypotension or hypoxemia, such as dehydration, shock, and sepsis. Major surgical procedures can involve prolonged periods of hypoperfusion, which are exacerbated by vasodilating anesthetic agents. The other major cause of ...

The hemolytic anemias are a group of disorders in which red blood cell survival is reduced, either episodically or continuously. The bone marrow has the ability to increase erythroid production up to eightfold in response to reduced red cell survival, so anemia will be present only when the ability of the bone marrow to compensate is outstripped. This will occur when red cell survival is extremely short or when the ability of the bone marrow to compensate is impaired for some second reason. Since red blood cell survival is normally 120 days, in the absence of red cell production the hematocrit will fall at the rate of approximately 1/100 of the hematocrit per day, which translates to a decrease in the hematocrit reading of approximately 3% per week. For example, a fall of hematocrit from 45% to 36% over 3 weeks need not indicate hemolysis, since this rate of fall would result simply from cessation of red blood cell production. If the hematocrit is falling at a rate faster than that du...

THE THALASSEMIAS Essentials of Diagnosis Microcytosis out of proportion to the degree of anemia. Positive family history or lifelong personal history of microcytic anemia. Abnormal red blood cell morphology with microcytes, acanthocytes, and target cells. In -thalassemia, elevated levels of hemoglobin A2 or F. General Considerations The thalassemias are hereditary disorders characterized by reduction in the synthesis of globin chains ( or ). Reduced globin chain synthesis causes reduced hemoglobin synthesis and eventually produces a hypochromic microcytic anemia because of defective hemoglobinization of red blood cells. Thalassemias can be considered among the hypoproliferative anemias, the hemolytic anemias, and the anemias related to abnormal hemoglobin, since all of these factors play a role in pathogenesis. Normal adult hemoglobin is primarily hemoglobin A, which represents approximately 98% of circulating hemoglobin. Hemoglobin A is formed from a tetramer—two chains and two c...

Many chronic systemic diseases are associated with mild or moderate anemia. Common causes include chronic infection or inflammation, cancer, and liver disease. The anemia of chronic renal failure is somewhat different in pathophysiology, involving reduced production of erythropoietin, and is usually more severe. Hepcidin has been identified as an important mediator of sequestration of iron within macrophages, and upregulation of hepcidin in response to mediators of inflammation, such as IL-6, is an important cause of anemia of chronic disease. Clinical Findings SYMPTOMS AND SIGNS The clinical features are those of the causative condition. The diagnosis should be suspected in patients with known chronic diseases; it is confirmed by the findings of low serum iron, low TIBC, and normal or increased serum ferritin (or normal or increased bone marrow iron stores). In cases of significant anemia, coexistent iron deficiency or folic acid deficiency should be suspected. Decreased dietary inta...

Essentials of Diagnosis Serum ferritin < 12 mcg/L. Caused by bleeding in adults unless proved otherwise. Responds to iron therapy. General Considerations Iron deficiency is the most common cause of anemia worldwide. The causes are listed in Table 13–3. Aside from circulating red blood cells, the major location of iron in the body is the storage pool as ferritin or as hemosiderin and in macrophages. Table 13–3. Causes of iron deficiency. Deficient diet Decreased absorption Increased requirements Pregnancy Lactation Blood loss Gastrointestinal Menstrual Blood donation Hemoglobinuria Iron sequestration Pulmonary hemosiderosis The average American diet contains 10–15 mg of iron per day. About 10% of this amount is absorbed. Absorption occurs in the stomach, duodenum, and upper jejunum. Dietary iron present as heme is efficiently absorbed (10–20%) but nonheme iron less so (1–5%), largely because of interference by phosphates, tannins, and other food constituents. Sm...

GENERAL APPROACH TO ANEMIAS Anemia is present in adults if the hematocrit is less than 41% (hemoglobin < 13.5 g/dL) in males or less than 37% (hemoglobin < 12 g/dL) in females. Congenital anemia is suggested by the patient’s personal and family history. Poor diet results in folic acid deficiency and contributes to iron deficiency, but bleeding is much more commonly the cause of iron deficiency in adults. Physical examination includes attention to signs of primary hematologic diseases (lymphadenopathy, hepatosplenomegaly, or bone tenderness). Mucosal changes such as a smooth tongue suggest megaloblastic anemia. Anemias are classified according to their pathophysiologic basis, ie, whether related to diminished production or accelerated loss of red blood cells (Table 13–1), or according to cell size (Table 13–2). The diagnostic possibilities in microcytic anemia are iron deficiency, thalassemia, and anemia of chronic disease. A severely microcytic anemia (mean cell volume [...