原发性肾小球疾病英文课件

第二章 原发性肾小球疾病 Chapter 2 Primary Glomerular Disease 概述 肾小球疾病（Glomerular disease）是指病变位于肾小 球的一类以血尿，蛋白尿，水肿和髙血压等为主要表现 的肾脏疾病，可导致终末期肾脏病(End Stage Renal Disease, ESRD)，分原发性，继发性和遗传性。 原发性病因常不明确，故又称之为特发性，肾小球病变 是唯一或主要病变。继发性病因常比较明确（如系统性 红斑狼疮和糖尿病等），肾小球病变为全身性疾病的一 个部分，病理变化类型并不单一。而遗传性肾小球疾病 ，是遗传基因变异所致的肾小球疾病（如Alport综合征 和Fabry病等）。 分类 原发性肾小球疾病病理分型(根据WHO 1995年制定 的标准)： n微小病变性肾小球病 n局灶节段性肾小球肾炎/肾小球硬化 n弥漫性肾小球肾炎 膜性肾病 增生性肾炎 系膜增生性肾小球肾炎 毛细血管内增 生性肾小球肾炎 腹增生性肾小球肾炎/系膜毛细血管 性肾小球肾炎 新月体(和坏死)性肾小球肾炎 增生硬化性/硬化性肾小球肾炎 n免疫反应 n肾小球免疫损伤的机制 n肾小球疾病的进展 发病机制 (The mechanisms of glomerular injury) 临床表现 n蛋白尿 Proteinuria n血尿 Hematuria n水肿 Edema n高血压 Hypertension n肾功能损害 Renal Insufficiency Nephrotic syndrome Figure 1. Nephrotic edema. Figure 2. Nephrotic edema. Nephrotic syndrome This is characterized by proteinuria (Typically 3.5g/24h), hypoalbuminemia ( less than 30g/dL ) and edema. Hyperlipidaemia is also present. Primary and secondary causes are summarized in Table 2, 3a,b In practice, many clinicians refer to “nephrotic range” proteinuria regardless of whether their patients have the other manifestations of the full syndrome because the latter are consequences of the proteinuria. Pathophysiology Proteinuria Proteinuria can be caused by systemic overproduction, tubular dysfunction, or glomerular dysfunction. It is important to identify patients in whom the proteinuria is a manifestation of substantial glomerular disease as opposed to those patients who have benign transient or postural (orthostatic) proteinuria. Heavy proteinuria (albuminuria) Figure 3. Zandi-Nejad K et al. Kidney Int. Suppl 2004;92:S76-S89 图1、导致蛋白尿肾病的小管间质炎症及肾硬化的某些事件 图2、肾脏对滤过白蛋白处理(回吸收) 的旁路 Russo LM et al. Kidney Int. Suppl 2004;92:S67-S68 Hypoalbuminemia nHypoalbuminemia is in part a consequences of urinary protein loss. It is also due to the catabolism of filtered albumin by the proximal tubule as well as to redistribution of albumin within the body. This in part accounts for the inexact relationship between urinary protein loss, the level of the serum albumin, and other secondary consequences of heavy albuminuria . The salt and volume retention in the NS may occur through at least two different major mechanisms. nIn the classic theory, proteinuria leads to hypoalbuminemia, a low plasma oncotic pressure, and intravascular volume depletion. Subequent underperfusion of the kidney stimulates the priming of sodium-retentive hormonal systems such as the RAS axis, causing increased renal sodium and volume retention, In the peripheral capillaries with normal hydrostatic pressures and decreased oncotic pressure, the Starling forces lead to transcapillary fluid leakage and edema . Edema nIn some patients, however, the intravascular volume has been measured and found to be increased along with suppression of the RAS axis. An animal model of unilateral proteinuria shows evidence of primary renal sodium retention at a distal nephron site, perhaps due to altered responsiveness to hormones such as atrial natriuretic factor. Here only the proteinuric kidney retains sodium and volume and at a time when the animal is not yet hypoalbuminemic. Thus, local factors within the kidney may account for the volume retention of the nephrotic patient as well. Edema Figure 4. Hyperlipidemia nMost nephrotic patients have elevated levels of total and low-density lipoprotein (LDL) cholesterol with low or normal high-density lipoprotein (HDL) cholesterol . Lipoprotein (a) Lp(a) levels are elevated as well and return to normal with remission of the nephrotic syndrome. Nephrotic patients often have a hypercoagulable state and are predisposed to deep vein thrombophlebitis, pulmonary emboli, and renal vein thrombosis. Cause Table 2 CAUSES OF THE NEPHROTIC SYNDROME Table 3a NEPHROTIC SYNDROME ASSOCIATED WITH SPECIFIC CAUSES (“SECONDARY” NEPHROTIC SYNDROME) Table 3b NEPHROTIC SYNDROME ASSOCIATED WITH SPECIFIC CAUSES (“SECONDARY” NEPHROTIC SYNDROME) Pathology patterns and clinical presentations of idiopathic nephrotic syndome nIn adults, the nephrotic syndrome is a common condition leading to renal biopsy. In many studies, patients with heavy proteinuria and the nephrotic syndromes have been a group highly likely to benefit from renal biopsy in terms of a change in specific diagnosis, prognosis, and therapy. nSelected adult nephrotic patients such as the elderly have a slightly different spectrum of disease, but again the renal biopsy is the best guide to treatment and prognosis (Table 2, 3). Renal biopsy PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME n Minimal Change Disease n Focal Segmental Glomerulosclerosis n Membranous Nephropathy n Membranoproliferative Glomerulonephritis (MPGN) Figure 5a. Pathology of glomerular disease. Light microscopy. (a) Normal glomerulus; minimal change disease. Table 4 PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME n Minimal Change Disease n Focal Segmental Glomerulosclerosis n Membranous Nephropathy n Membranoproliferative Glomerulonephritis(MPGN) Figure 5b. Segmental sclerosis; focal segmental glomerulosclerosis. Figure 6. Light microscopic appearances in focal segmental glomerulosclerosis. Segmental scars with capsular adhesions in otherwise normal glomeruli. Table 5 PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME n Minimal Change Disease n Focal Segmental Glomerulosclerosis n Membranous Nephropathy n Membranoproliferative Glomerulonephritis(MPGN) Figure 7a. Early MN: a glomerulus from a patient with severe nephrotic syndrome and early MN, exhibiting normal architecture and peripheral capillary basement membranes of normal thickness (Silvermethenamine 400). Figure 7b Morphologically advanced MN Figure 7c. Morphologically more advanced MN (same patient as in (b) Table 6 PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME n Minimal Change Disease n Focal Segmental Glomerulosclerosis n Membranous Nephropathy n Membranoproliferative Glomerulonephritis(MPGN) Figure 8. Pathology of membranoproliferative glomerulonephritis type I. (a) Light microscopy shows a hypercellular glomerulus with accentuated lobular architecture and a small cellular crescent (methenamine silver). Table 7 Diagnosis and Differential diagnosis n Initial evaluation of the nephrotic patient includes laboratory tests to define whether the patient has primary, idiopathic nephrotic syndrome or a secondary cause related to a systemic disease. nCommon screening tests include the fasting blood sugar and glycosylated antibody test for rheumatoid disease, and the hemoglobin tests for diabetes, and antinuclear serum complement, which screen for many immune complex-mediated disease , In selected patients, cryoglobulins, hepatitis B and C serology, anti-neutrophil cytoplasmic antibodies (ANCA), anti GBM antibodies, and other tests may be useful. Once secondary causes have been