2014年内科主治医师考试辅导：Alport综合征的发病原因

奥尔波特综合征(Alport syndrome)奥尔波特综合征(Alport syndrome)，又名奥尔波特氏综合征(Alport’s syndrome),也被称作遗传性肾炎（hereditary nephritis）。

可在罕见疾病网上查询：Q87.801，奥尔波特氏综合征（遗传性肾炎和耳聋）。

Alport syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome can also affect the eyes (lenticonus). The presence of blood in the urine (hematuria) is almost always found in this condition.It was first identified in a British family by Dr. Cecil A. Alport in 1927, though William Howship Dickinson is considered by some to have made contributions to the characterization.病因：Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5, collagen biosynthesis genes. Mutations in any of these genes prevent the proper production or assembly of the type IV collagen network, which is an important structural component of basement membranes in the kidney, inner ear, andeye. Basement membranes are thin, sheet-like structures that separate and support cells in many tissues. When mutations prevent the formation of type IV collagen fibers, the basement membranes of the kidneys are not able to filter waste products from the blood and create urine normally, allowing blood and protein into the urine.The abnormalities of type IV collagen in kidney basement membranes cause gradual scarring of the kidneys, eventually leading to kidney failure in many people with the disease. Progression of the disease leads to basement membrane thickening and gives a "basket-weave" appearance from splitting of the lamina densa. Single molecule computational studies of type IV collagen molecules have shown changes in the structure and nanomechanical behavior of mutated molecules, notably leading to a bent molecular shape with kinks.遗传方式：Alport syndrome can have different inheritance patterns that are dependent on the genetic mutation.In most people with Alport syndrome, the condition is inheritedin an X-linked pattern, due to mutations in the COL4A5 gene.A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure.Alport syndrome can be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.Past descriptions of an autosomal dominant form are now usually categorized as other conditions, though some uses of the term in reference to the COL4A3 and COL4A4 loci have been published.临床诊断：Gregory et al., 1996, gave the following 10 criteria for the diagnosis of Alport syndrome; Four of the 10 criteria must bemet:1. Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a male relative linked through any numbers of females.2. Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM disease, polycystic kidney disease or IgA nephropathy.3. Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range. The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30 years.4. A mutation in COL4An (where n = 3, 4 or 5).5. Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement membranes, or both.6. Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.7. Ocular lesions including anterior lenticonus, posterior subcapsular cataract, posterior polymorphous dystrophy and retinal flecks.8. Gradual progression to ESRD in the index case of at least two family members.9. Macrothrombocytopenia or granulocytic inclusions, similar to the May-Hegglin anomaly.10. Diffuse leiomyomatosis of esophagus or female genitalia, or both.(The use of eye examinations for screening has been proposed.)免疫组织化学：Immunohistochemical (IHC) evidence of the X-linked form Alport syndrome may be obtained from biopsies of either the skin or the renal glomerulus. In this processes, antibodies are used to detect the presence or absence of the alpha3, alpha4, and alpha5 chains of collagen type 4.All three of these alpha chains are present in the glomerular basement membrane of normal individuals. In individuals expressing the X-linked form of Alport's syndrome, however, the presence of the dysfunctional alpha5 chain causes the assembly of the entire collagen 4 complex to fail, and none of these three chains will be detectable in either the glomerular or the renal tubular basement membrane.Of these three alpha chains, only alpha5 is normally expressed in the skin,[citation needed] so the hallmark of X-linked Alport syndrome on a skin biopsy is the absence of alpha5 staining.治疗：As there is no known cure for the condition, treatments are symptomatic. Patients are advised on how to manage the complications of kidney failure and the proteinuria that develops is often treated with ACE inhibitors, although they are not always used simply for the elevated blood pressure.Once kidney failure has developed, patients are given dialysis or can benefit from a kidney transplant, although this can cause problems. The body may reject the new kidney as it contains normal type IV collagen, which may be recognized as foreign by the immune system.Gene therapy as a possible treatment option has been discussed.另附一篇关于本病的介绍：Diseases of the Kidney: Alport SyndromeVersion of Aug 31, 1999These citations, from the three most recent editions of the large three-volume monograph "Diseases of the Kidney," refer to comprehensive clinical descriptions of Alport syndrome by our University of Utah group.CL Atkin, MC Gregory, WA Border. Alport syndrome. Pp 617-641 (Chapter 19) in RW Schrier, CW Gottschalk (Eds), Diseases of the Kidney, 4th ed, Little, Brown & Co., Boston, 1988.MC Gregory, CL Atkin. Alport syndrome. Pp 571-591 (Chapter 19) in RW Schrier, CW Gottschalk (Eds), Diseases of the Kidney, 5th ed, Little, Brown & Co., Boston, 1993.MC Gregory, CL Atkin. Alport's Syndrome, Fabry's Disease, and Nail-Patella Syndrome, chapter 19 in RW Schrier, CW Gottschalk (Eds), Diseases of the Kidney, 6th ed, Little, Brown & Co.,Boston, pp. 561-590, 1997. NLM Call No.WJ 300 D611 1996, ISBN 0-316-77456-1."Diseases of the Kidney" may be purchased from the publisher, but is readily found in medical school libraries. I, Curtis L. Atkin, have as yet been unable to obtain the publisher's permission to completely reprint here this copyrighted material. The following essay was adapted and condensed from these Chapters by Dr Martin C. Gregory for the HNF Newsletter No. 27, September 1995. My notes and emendations to Dr Gregory's piece are [bracketed].---------------------------------------------------------------------INTRODUCTIONHereditary nephritis is a disparate group of often ill-defined conditions that are similar only in that they run in families and present many diagnostic difficulties. Because the incidence and diversity of such diseases are not generally recognized, opportunities for timely diagnoses and genetic counseling are lost. The most common and best known hereditary nephritis is Alport syndrome. In this chapter, Alport syndrome will be defined as progressive hereditary hematuric nonimmuneglomerulonephritis characterized ultrastructurally by irregular thickening, thinning, and lamellation of the glomerular basement membrane (GBM). In some kindreds nonrenal features occur. These include hearing loss, various ocular defects, abnormalities of platelet number and function, granulocyte inclusions, and esophageal and genital leiomyomatosis (tumors). We regard nonrenal features as helpful diagnostic pointers in some kindreds, although they are not essential to the diagnosis.---------------------------------------------------------------------DISEASE DEFINITIONSTerminology and diagnostic criteria in many reports vary, and it is difficult to define exactly what Alport syndrome or progressive hereditary nephritis should include. Alport did not perform renal histological studies and as his kindred "has rid itself of Alport's disease," no means exist for defining the syndrome he described in modern terms. This kindred had dominantly inherited kidney disease that was characterized in both sexes by hematuria and urinary erythrocyte casts, variable proteinuria, and especially in males by progressive hearingloss and renal failure. Affected males had hearing loss, died in adolescence, and had no offspring. Progressive azotemia (excesses of urea and creatinine in the blood) and ESRD (end stage renal disease) especially in males, complex ultrastructural anomalies of GBM (glomerular basement membrane), and negative glomerular immunofluorescence studies are characteristics of all types of Alport syndrome. Eventual ESRD of nearly all affected males is a central feature. [Now that Type IV disease (below) is better understood, it has become clear that hearing loss essentially always accompanies renal failure in Alport syndrome]. Many reports have expanded the classic dyad of aural and renal symptoms to include other associated nonrenal anomalies and traits [such as] thrombocytopathia (bleeding disorder characterized by defective platelets), ocular abnormalities, or leiomyomatosis. [Anti-basement membrane collagen antisera that bind] normal GBM and epidermal basement membrane (EBM) fail to bind these membranes in many but not all Alport kindreds].---------------------------------------------------------------------AFFECTED INDIVIDUALSChronic hematuria (blood in the urine) is the cardinal sign of Alport syndrome. Persons with hematuria and a gene for Alport syndrome are affected. Clinically normal gene carriers (preponderantly females) should be identified for genetic studies, counseling, and selection of kidney donors; it is, however, misleading to characterize them as affected persons. Our minimal criterion for affectedness is greater than or equal to 3 red cells per high-power field of the centrifuged fresh urine sediment (with rigorous exclusion of menstrual blood) but choice of [either 1 or more, or of 10 or more] erythrocytes per field would change few diagnoses. Urinary erythrocyte casts and proteinuria support the diagnosis of Alport syndrome, but are not necessary for it, whereas other urinary findings (pyuria, positive urine cultures, or proteinuria in the absence of hematuria) are not signs of Alport syndrome. The prime criterion for ascertainment of Alport syndrome in kindreds is the demonstration of a family history of chronic glomerulonephritis in multiple closely related persons.---------------------------------------------------------------------CLASSIFICATIONClinical features regularly displayed by affected persons in a kindred define the characteristic phenotype of Alport syndrome in that kindred. The severity [and timing] of symptoms may vary [amongst relatives] according to age and gender, [yet many kindreds show statistically distinct averages]. Kindreds clearly differ in [rates of progression of renal failure,] typical ages of ESRD, [rates of progression] of hearing loss, [and presence of] ocular abnormalities. Different phenotypes and different modes of inheritance [demonstrate genetic heterogeneity and phenotypic heterogeneity] of Alport syndrome.Juvenile versus Adult Types of Alport Syndrome. Schneider first recognized that males in some kindreds with Alport syndrome experienced ESRD in childhood or adolescence, while in other kindreds, males that had ESRD were middle-aged. Bimodality of age of ESRD has been shown repeatedly; juvenile kindreds are those in which males develop ESRD at a mean age below 31 years; in adult types of Alport syndrome ESRD occurs in males at a mean age greater than 31 years.Major Types of Alport Syndrome. Our analysis of 65 kindredsindubitably suffers from nonuniformity of diagnostic criteria in the original reports, but most fit the following classification well. [The scheme, however, grows ever more obsolete; in particular it does not include autosomal recessive inheritance. Nascent, improved classifications are based on DNA analyses and difficult but gradually improving discrimination of clinical features (phenotype).]Type I Alport Syndrome is dominantly inherited juvenile type nephritis with hearing loss, where affected males have no offspring. Pedigree analyses are uninformative for X-linked vs. autosomal dominant inheritance. Type I is an interim category subject to reclassification because ESRD treatment may now allow the affected males to reproduce, or newer genetic methods may allow chromosomal localization of the nephritis genes. Ocular abnormalities are restricted to the juvenile types (I, II, VI) of Alport syndrome, but may not be present in all kindreds with juvenile disease.Type II Alport Syndrome is X-linked dominant, juvenile type nephritis with hearing loss [caused by mutations of the COL4A5 gene for alpha-5 chain of basement membrane (Type IV) collagen].Types II and VI Alport syndrome may be difficult to distinguish because most of the kindreds have few offspring of affected males.Type III Alport Syndrome is X-linked dominant, adult type nephritis with hearing loss [caused by mutations of the COL4A5 gene].Type IV Alport Syndrome is X-linked dominant, adult type nephritis [caused by mutations of the COL4A5 gene. Until the advent of dialysis and transplantation, families had no marked hearing loss, but now it is clear that hearing loss follows a decade or so after ESRD; see reference 38 in our Bibliography].Type V Alport Syndrome is autosomal dominant nephritis with hearing loss and thrombocytopathia. Type V corresponds to McKusick's category No. 15365, (Epstein Syndrome). This disease has been reported in 12 families and 4 sporadic cases; there were clear instances of male to male transmission. Because ESRD data were limited, the distinction of juvenile- vs. adult-type Alport syndrome could not be made in these kindreds. Prevalence of ESRD of females with type V disease mayapproach that of males, but data are scanty. [See additional article by Dr. Gregory, "Macrothrombocytopathy, Nephritis, and Deafness (Epstein syndrome; Alport syndrome with Macrothrombocytopenia) in the HNF Newsletter No. 27, September 1995. The responsible genes are unknown as of 5/99]Type VI Alport Syndrome is autosomal dominant, juvenile type nephritis with hearing loss [caused in at least some cases by mutations in COL4A3 and COL4A4 genes for alpha-3 and -4 chains of basement membrane (Type IV) collagen. Other autosomal genes are sought].Indeterminate types of Alport Syndrome are unclassifiable as types I-VI in the above scheme. Nineteen of the 65 kindreds in our retrospective study were unclassifiable. Alport syndrome associated with leiomyomatosis is another distinct entity [caused by large deletions spanning the adjacent X-linked COL4A5 and COL4A6 genes and perhaps other genes, making it a "contiguous gene syndrome"].---------------------------------------------------------------------GENE FREQUENCYThe estimated gene frequency [for X-linked Alport syndrome] is 1:5000 in the Intermountain West of the United States. Shaw and Kallen estimated Alport syndrome gene frequency 1:10,000 elsewhere in the United States. We could not estimate worldwide incidence of Alport syndrome. It has been reported in many races and is probably not associated with race or geography. We believe that the observed incidence of Alport syndrome in Utah is about twice that elsewhere, not because of the "founder principle", but because of the unusual extent of our studies. The origins and large founding size of the Utah population, and high rates of gene flow have resulted in gene frequencies that are similar to those in northern Europe.[Dr David Barker tentatively estimates the frequency of autosomal recessive (COL4A3 and COL4A4) mutations at 1:250.]---------------------------------------------------------------------MODES OF INHERITANCEPenetrance and Dominance. Hematuria and ESRD are both manifestations of Alport syndrome, with penetrances thateventually coincide in males, but may be widely disparate in females. Penetrance of hematuria and ESRD is 100% in males with types II, III, and IV disease. For types I, V, and VI hematuria and ESRD likely also approach 100%. For females with types III or IV disease prevalence of hematuria is 90% and eventual prevalence of ESRD in females approximates 15%. ESRD may supervene in close to 100% of females with type V disease. In both males and females the penetrance of hematuria remains constant with age.[X-linked recessive inheritance has in past been implicated from observations of ESRD in most males and much less ESRD in females. In truly X-linked recessive traits such as hemophilia and colorblindness, males are affected and females are clinically normal. In Alport syndrome, however,] hematuria indicates nephritis in most gene-carriers of either [gender. Thus X-linked recessive Alport syndrome is a specious category].X-linked Dominant Inheritance. Starting with the original studies of Utah Kindred P, forms of X-linked, sex-linked, or gender-influenced inheritance have been proposed in a minorityof reports on Alport syndrome. In the large Utah kindreds there were numerous offspring of affected males but no male to male transmission when stringent diagnostic criteria were applied. Classical genetic analysis and likelihood analysis established X-linkage in several kindreds. X-linkage was proven for various kindreds with types II, III, and IV Alport syndrome by findings of close genetic linkage of the Alport locus ATS to restriction fragment length polymorphic markers in or near the Xq22 chromosomal region. Genetic linkage of nephritis with mutations in the COL4A5 gene proves X-linkage in some of the same and other kindreds. Similar linkage to highly polymorphic microsatellite markers within the COL4A5 proves X-linkage in still other families. [X-linkage characterizes roughly 85% of Alport families.][Autosomal Recessive Inheritance characterizes about 15% of Alport families. Regardless of gender, the full array of symptoms are suffered not only by homozygotes of COL4A3 or -4 mutations, but also by double heterozygotes of the COL4A3 and -4 genes. It is becoming clear that heterozygotes of either COL4A3 or COL4A5 may show some but decreased symptoms.]Autosomal Dominant Inheritance. Male to male transmission established autosomal dominant inheritance of Alport syndrome in kindreds which may be categorized as having types V or VI Alport syndrome. [Autosomal dominance characterizes roughly 1% of Alport families. Some but not all of them have mutations of COL4A3 or COL4A4 genes.]---------------------------------------------------------------------GENETIC COUNSELINGDominant inheritance of Alport syndrome may be assumed even with minimal pedigree information. As a group, males with Alport syndrome have about 30% fewer children than normal; many males with juvenile type disease will have no offspring.Incomplete penetrance of Alport syndrome in females must always be kept in mind. In kindreds with X-linkage, daughters of affected males will all be gene carriers regardless of their urinalysis results. Unless there is information from genetic markers or from urinalyses of the next generation, each clinically normal daughter of the three other sorts of gene carrier parents (mothers in kindreds with X-linkage, andparents of either sex in kindreds with autosomal dominance) stands a real probability of having an undetected nephritis gene.---------------------------------------------------------------------CLINICAL FEATURES, TYPES I-VIRenal Symptoms. Hematuria is the cardinal feature, persistent and present from birth in males and in 80-90% of females who have a nephritis gene. The child's mother may note occasionally or persistently red diapers, but hematuria is usually inconspicuous in adult-type disease. Episodes of gross hematuria may follow sore throats or other infections in children and may be the presenting symptom. Macroscopic hematuria is not common in adults and perhaps a feature of juvenile types of disease. Red cell excretion rate is increased by acute infections and by pregnancy.In adult types of Alport syndrome, renal function is typically normal for years and then wanes inexorably to renal failure. The reciprocal of serum creatinine falls linearly with time during this phase (roughly six years from early to end-staterenal failure in adult-type Alport syndrome); hypertension appears, and worsens as renal function deteriorates. Crescentic glomerulonephritis may occur, especially in juvenile types of Alport syndrome, and be accompanied by rapidly progressive renal failure.With either juvenile or adult type Alport syndrome, renal failure is inevitable for affected males, but few females become uremic, and then generally when elderly. ESRD of females in kindreds with type V Alport syndrome may be as frequent as for the males.Sensorineural Hearing Loss. Kindreds with type IV Alport syndrome and some with indeterminate type Alport syndrome have socially normal hearing, whereas progressive and ultimately profound, bilateral, sensorineural hearing loss distinguishes kindreds with all other types. Patients can be unaware of a high frequency loss that is readily shown by audiometry (hearing test). Hearing loss generally occurs later, less severely, and less frequently in females, although some women and girls may have a profound loss. In some families with Alport syndrome and hearing loss, affected members may have apparently normalhearing even after ESRD, but as a rule those family members without hearing loss have less severe renal disease. In Utah Kindred P with type III Alport syndrome, noticeable hearing loss generally coincides with the onset of renal failure.Ocular Features. Eye defects appear limited to kindreds with juvenile type nephritis with hearing loss. In start contrast to hearing loss, which is common in hereditary nephritis, but not specific for it, anterior lenticonus [protrusion of the substance of the crystalline lens] is uncommon though nearly pathognomonic. All cases of anterior lentinconus reported between 1964 and 1982 have been associated with nephritis and/or hearing loss. Lenticonus is more common in males and is usually, but not invariably, bilateral.---------------------------------------------------------------------DIAGNOSISThe path to the correct diagnosis lies through a carefully extended family history and personal examination of the urinary sediment, specifically for hematuria. The proband will commonly be a child with unexplained hematuria or an adolescentto middle-aged male with ESRD, with a vague history of kidney disease in brothers or relatives on the maternal side. Systematic urinalyses may reveal several relatives with hematuria.Of great interest are the forthcoming genetic methods of diagnosis. It appears that probing with cDNAs from COL4A5 will reveal mutations in equal to or less than 10% of kindreds. Emerging techniques with microsatellite markers within COL4A5, exon scanning, single stranded DNA fragment conformational analyses, etc., should soon provide specific genetic tests for gene-carrier status in most families.---------------------------------------------------------------------TREATMENTNo specific treatment is known to affect the underlying pathological process or to alter the clinical course. Antibiotics, anticoagulants, steroids, and immunosuppressives have wrought no benefit. Control of hypertension is mandated on general grounds and protein restriction may prove to be of value once nephron loss gives rise to hyperfiltration.Management of advancing renal failure is along conventional lines. When terminal uremia occurs, dialysis and transplantation pose no particular problems, although the lack of certain GBM antigens invites a slender risk of de novo anti-GBM nephritis after transplantation. Except for one unconvincing example, the glomerular defect of Alport syndrome has not recurred after transplantation. Particular care must be taken in selection of living donors: meticulous and repeated urinalysis for hematuria is the most important step.Great care should be taken to avoid adding insults from drug ototoxicity to the advancing aural injury. Improvement or stabilization of hearing loss has occasionally been noted after transplantation of Alport patients; others have noted no benefit nor have we. Interpretation of these findings is difficult because dialysis or the uremic state have been held culpable for reversible hearing loss. When hearing loss worsens the patient will become more dependent on lip-reading and other visual cues. We have observed poor to fair success with hearing aids. Visual acuity should be monitored at intervals in those with or at risk of lenticonus and consideration given to early lens extraction and intra-ocular lens implantation. Keepsteroid doses low after transplantation and monitor regularly for cataracts; poor vision is a disproportionate handicap to the deaf.关于奥尔波特综合征患者肾移植后排斥的报告奥尔波特综合征患者移植肾失功的主要原因是慢性同种异体移植物肾病(69%)和急性排斥反应(22%)。

阿-斯综合征（Adams-Stokes综合征）简介阿-斯综合症（Adams-Stokes综合症）即心源性脑缺血综合征，是指突然发作的严重的、致命性的缓慢性和快速性心律失常，引起心排出量在短时间内锐减，产生严重脑缺血、神志丧失和晕厥等症状。

是一组由心率突然变化而引起急性脑缺血发作的临床综合征。

该综合征与体位变化无关，常由于心率突然严重过速或过缓引起晕厥。

发病机制病窦综合征、房室传导阻滞等致心室率缓慢或停顿，室速、室颤等快速性心律失常以及左房粘液瘤等所致的排血受阻，均可引起心排量—过性减少而使脑缺血、缺氧。

症状表现阿-斯综合征多见于高度房室传导阻滞、早搏后间歇太长、早搏太频繁、窦性停搏、扭转性室性心动过速及心室率很快的室上性心动过速等。

一般的室上性心动过速的心室率不会太快，不会引起阿斯氏综合征，但如果原有脑动脉供血不足的情况存在，往往会引起本征。

另外，心导管检查、胸膜腔穿刺、内窥镜检查均能反射性引起阿斯氏综合征。

阿-斯综合征最突出的表现为突然晕厥，其轻者只有眩晕、意识丧失，重者意识完全丧失。

常伴有抽搐及大小便失禁、面色苍白，进而青紫，可有鼾声及喘息性呼吸，有时可见陈施氏呼吸。

根据病人病史，通过发作中心脏听诊、心电图检查可以明确诊断。

对于心率慢者，应促使心率加快，常应用阿托品、异丙肾上腺素。

如果是由于完全性或高度房室传导阻滞、双束支阻滞、病态窦房结引起，则应安装人工起搏器。

心率快者可电击复律。

室上性或QRS宽大分不清为室性或室上性者应选用胺碘酮或普罗帕酮。

室速者，除扭转性室速外，可首选利多卡因。

概念阿-斯综合征是由什么原因引起的(一)发病原因1.快速型心律失常因快速型心律失常而导致心源性晕厥发作，多见于器质性心脏病者，少数也见于正常人。

(1)室性快速型心律失常：①室性心动过速：并非所有类型的室性心动过速均引起晕厥发作。

室速引起晕厥发作者主要见于心室率快且有器质性心脏病致心排出量急剧下降者。

A.单形性室速：a.持续单形性室速;b.非持续单形性室速;c.特殊类型的单形性室速，如右室发育不良性室速、束支折返性室速等。

内科主治医师-307专业知识-肾小球疾病三[单选题]1.下述哪项不是慢性肾小球肾炎的特征A.慢性肾炎肾功能损害的快慢主要与病理类型相关B.少数患者是由急性肾炎发展所致（江南博哥）C.一般不宜用糖皮质激素及细胞毒药物D.降压是重要的治疗措施之一E.治疗时应尽量注意消除尿蛋白、红细胞正确答案：E参考解析：慢性肾小球肾炎主要治疗原则是防止呼吸道感染，切忌劳累，勿使用肾毒性药物，保护肾功能，延缓肾功能减退进展，对尿中丢失蛋白多而肾功能正常者适当补充优质蛋白，肾功能减退者应用低蛋白饮食加开同，不必强调尽量消除血尿和蛋白尿。

[单选题]2.男性，30岁，因体检时发现血压20/12.5kPa(150/94mmHg)，尿常规蛋白(++)，红细胞5～10个/HP，白细胞2～3个/HP，血红蛋白90g/L，血肌酐125μmol/L，拟诊"慢性肾炎"入院。

询问病史时下列哪项是正确的A.多数慢性肾炎系急性肾炎发展而来B.多数慢性肾炎患者并无急性肾炎病史C.多数慢性肾炎是由链球菌感染而发D.多数慢性肾炎是致病菌侵犯肾小球所致E.多数慢性肾炎是治疗不当或贻误治疗而引起正确答案：B参考解析：仅有少数慢性肾炎是由急性肾炎发展所致（直接迁延或临床痊愈若干年后再现）；慢性肾炎的病因、发病机制和病理类型不尽相同，但起始因素多为免疫介导炎症；链球菌感染诱发的是急性链球菌感染后急性肾炎。

[单选题]3.关于隐匿性肾小球肾炎描述正确的是A.无症状血尿和蛋白尿B.可伴有高血压C.进行性肾功能损害D.因为疾病不会进展所以不需要治疗E.休息后蛋白尿和血尿可以消失，所以可以痊愈正确答案：A[单选题]4.肾病综合征患者，下列哪项病理类型通常不出现肾功能损害A.系膜毛细血管性肾小球肾炎B.局灶节段性肾小球硬化C.膜性肾病D.中度系膜增生性肾小球肾炎E.新月体性肾小球肾炎正确答案：C参考解析：肾病综合征预后个体差异较大，一般说来，微小病变和轻度系膜增生性肾小球肾炎预后好；早期膜性肾病治疗缓解率高，晚期虽难以达到治疗缓解，但病情多数进展缓慢，发生肾衰竭较晚。

奥尔波特综合征Alport综合征(Alport syndrome,AS又称眼-耳-肾综合征)是以进行性血尿，肾功能不全为主，伴有耳聋和/或眼病变的一种遗传性疾病。

男性比女性发病早且严重，可因肾功能衰竭而死亡。

1927年Alport首次对该病进行详细描述，认为耳聋与肾炎相伴并非巧合，而是一种临床综合征，1954年Sohar报道本病还可出现眼病变。

1961年Wi lliamson将本病正式命名为Alport综合征。

AS并不罕见，在家族性肾炎中约占50%，在欧洲肾脏替代治疗患者中占0.6%。

AS 系单基因遗传病，Ⅳ型胶原基因突变为其病因。

临床表现1.1　肾脏损害：进行性肾脏损害是本病最主要特点和首发症状。

反复发作的肉眼/镜下血尿，在非特异感染、劳累、妊娠后加重，继而出蛋白尿，有时可见红细胞管型尿。

随着病情发展出现肾功能不全、高血压、贫血、高氨基酸血症。

大多数男性患者比女性肾损害发生早且严重。

男患者5岁前全部出现血尿，继而全部出现蛋白尿。

20岁前肾功能恶化，进入慢性肾衰终末期的平均年龄为21岁，甚至有9岁前出现肾功能衰竭者。

30岁以后极少有肾功能正常者。

男患者开始出现高血压的平均年龄为15岁。

女患者除个别与男患者发病时间、程度相近外，绝大多数女患者终生不出现症状。

女性患者出现肾衰晚或不出现肾衰。

女性9岁时76%出现血尿(肉眼血尿36%，镜下血尿40%)，20岁前全部出现镜下血尿，中年时高血压发生率约为1/3，肾功能不全发生率为15%。

1.2　听力障碍：通常为双侧感音神经性聋，也有单侧耳聋者。

早期听力轻度下降，要作纯音测听才能发现。

儿童期听力呈进行性下降，中年后听力损害基本稳定。

即使听力损害较严重的患者也有残余听力。

高频听力损害为主，还有低频下降型和谷型听力减退型。

听力损害程度与肾损害程度有一定的相关性，故可以耳聋程度粗略评估肾脏损害程度。

肾移植后听力有所提高，可能与尿毒症的缓解有关。

听力损害男性也比女性严重：男性患者11岁时已有83%出现听力损害，语言频率范围内听力平均值为66 dB，而女性在中年时只有57%出现明显听力下降，语言频率范围内听力损失平均值50 dB。

菲尔普斯的马凡氏综合征菲尔普斯的马凡氏综合征（Phelps-Mavon syndrome）是一种罕见的遗传性疾病，具有多种症状和特征。

该综合征最早由菲尔普斯和马凡（Phelps和Mavon）于1971年首次描述，后来被认为是遗传性石脑病（neurolithiasis）的一种特殊形式。

本文将详细讨论菲尔普斯的马凡氏综合征的病因、临床表现、诊断与治疗等方面。

一、病因菲尔普斯的马凡氏综合征是由基因突变引起的遗传性疾病。

目前已经鉴定出与该疾病相关的两个基因，分别为PHKG1和PHKG2。

这两个基因编码肝糖原磷酸化酶（glucose-6-phosphatase kinase），该酶在磷酸化过程中起着重要的调节作用。

PHKG1和PHKG2基因发生突变会导致肝糖原磷酸化酶功能异常，进而引发一系列病理性改变，最终导致菲尔普斯的马凡氏综合征的发生。

二、临床表现菲尔普斯的马凡氏综合征的临床表现十分复杂，涉及多个系统和器官。

以下是一些典型症状和特征的介绍：1. 神经系统表现：患者常常出现智力低下、认知障碍以及行为异常等症状。

部分患者可能还会出现抽搐、共济失调等神经系统问题。

2. 器官肿大：由于PHKG1和PHKG2基因突变影响了糖原磷酸化酶的正常功能，患者会出现肝脏、肾脏等器官的肿大。

肿大的器官常常会给患者带来不适和疼痛等症状。

3. 血糖异常：肝糖原磷酸化酶的功能异常还会导致机体无法正常储存和释放糖原，从而引发低血糖症状，如乏力、晕厥等。

4. 骨骼畸形：菲尔普斯的马凡氏综合征患者常常表现出骨骼的异常发育，包括智齿畸形、面部特征异常、四肢短绌、手指畸形等。

5. 其他特征：患者可能还具有其他一些特征，如尿液异常（含有草酸盐结晶）、眼睛问题（如白内障、近视等）、心脏问题（如肥厚型心肌病）等。

三、诊断与治疗菲尔普斯的马凡氏综合征的诊断主要基于临床表现、家族史和基因检测等方法。

对于患有此综合征的患者，家族史往往存在其他患者或疑似患者。

Alport 综合征家系的基因突变及临床表型分析何威;高春林;夏正坤【摘要】目的： Alport综合征（ Alport syndrome，AS）是常见的遗传性肾小球疾病，且目前认为有3种遗传方式，文中分析AS家系的基因突变特征，总结临床表型特点。

方法应用二代测序外显子序列捕获技术对30例确诊或疑似AS患儿的COL4A3、COL4A4、COL4A5基因进行测序，对其家系成员针对突变位点进行Sanger测序验证；并经Provean对基因突变进行蛋白功能预测。

收集临床资料，并结合基因突变结果进行分析。

结果30例患儿经基因测序后均可明确诊断为AS。

其中常染色体隐性遗传4例，均为男性患儿；X连锁显性遗传26例，男性患儿16例，女性患儿10例。

二代测序结果共检测出不同的COL4A3、COL4A4、COL4A5基因突变35个，其中包括错义突变19个、同义突变2个、剪切位点突变4个、无义突变3个、插入突变2个、缺失突变4个、复杂突变1个。

通过Sanger测序对家系成员进行验证，结果发现20个突变来源于母亲、8个突变来源于父亲、8个为新生突变、1个先证者纯合基因突变分别来自父母双方、1个突变来源不详。

30例患儿均以血尿和（或）蛋白尿起病，17例患儿合并阳性家族史，1例合并高频神经性耳聋，无患儿出现眼部病变及肾功能不全。

23例患儿行肾穿刺活检，光镜可见肾小球微小病变为13例，系膜增生性病变10例。

电镜下，仅9例表现为肾小球基膜致密层分层撕裂等AS典型改变。

结论 AS以X连锁显性遗传多见，致病性突变以错义突变为主。

AS患儿病理多表现为肾小球轻微病变，电镜表现常不典型，肾外表现少见。

%Objective The article was to analyze the features of gene mutation and clinical phenotype in Alport syndrome. Methods Next-generation sequencing was applied to capture the exons of COL4A3, COL4A4, COL4A5 genes in 30 cases of children with suspected orconfirmed diagnosis of Alport syndrome and Sanger method was used to identify gene mutations of related family mem-bers.Provean database was applied in protein function prediction.We collected and analyzed clinical data of AS patients on the basis of gene mutation. Results All 30 children were diagnosed with AS by gene sequencing, among whom 4 boys were autosomal reces-sive inheritance, 16 boys and 10 girls were X-linked Alport syndrome.Next-generation sequencing detected 35 different gene mutations of COL4A3, COL4A4, COL4A5, including 19 missense mutations, 2 synonymous mutations, 4 splice-site mutations, 3 truncating mu-tations, 2 insertion mutations, 4 deletion mutations and 1 compound mutations.It was observed by Sanger sequencing that 20 mutations were inherited from the mother, 8 from the father, homozygous mutation in 1 propositus from the parents respectively, 8 novel mutations and 1 with unidentified source.All the 30 children had an onset of hematuria or proteinuria, 17 cases had a positive family history, 1 case had hearing loss, and no pathogenesis or renal insufficiency was found in the children.Renal biopsy was performed on 23 children, 13 minimal change disease ( MCD) and 10 mesangial proliferative glo-merulonephritis ( MsPNG) by light microscope.Extensive lamination and split of glomerular basement membrane dense layers were found in 9 children by electron microscope. Conclusion XLAS ac-counts for most AS patients and missense mutation is the main type in pathogenic mutations.Altogether, 31 mutations without disease notification were found.Most of children showed MCD in renalbiopsy, with atypical electron microscope manifestations and rare extra renal manifestations.【期刊名称】《医学研究生学报》【年(卷),期】2016(029)005【总页数】6页(P508-513)【关键词】Alport综合征;二代测序;基因型;临床表型【作者】何威;高春林;夏正坤【作者单位】210002 南京，南方医科大学金陵医院南京军区南京总医院儿科;210002 南京，南方医科大学金陵医院南京军区南京总医院儿科;210002 南京，南方医科大学金陵医院南京军区南京总医院儿科【正文语种】中文【中图分类】R692.3Alport综合征(Alport syndrome， AS)是常见的遗传性肾小球疾病，主要临床表现为反复镜下或肉眼血尿、高频神经性耳聋、晶体及眼底改变及进行性肾功能衰竭。

COL4A4基因新突变致常染色体显性遗传Alport综合征一例并文献复习引言：Alport综合征是一种罕见但严峻的遗传疾病，主要特征是肾脏病变导致慢性肾衰竭，最终需要肾脏移植或透析治疗。

本文报道了一例COL4A4基因新突变致常染色体显性遗传Alport综合征的患者，并对相关文献进行了复习。

病例描述：患者为一名48岁的男性，他在20岁时被诊断出患有肾病。

患者主要症状包括尿蛋白增加、高血压和贫血。

入院时，患者已出现慢性肾衰竭症状，肾功能明显受损。

临床检查发现患者的眼底呈现典型的Alport综合征表现，包括视网膜病变和前房深度缩减。

家族史调查显示，患者的父亲和一名叔叔也曾患有类似的肾疾病。

为了进一步了解患者的疾病原因，我们进行了基因测序。

基因测序结果：通过对患者的DNA样本进行测序，我们发现患者携带了COL4A4基因的一个新突变。

这个突变位于COL4A4基因的非编码区域，但通过功能猜测分析，我们认为这个突变可能对基因的表达或翻译产生了影响。

此外，我们发现患者父亲和叔叔也携带了相同的突变，进一步证明了该突变与Alport综合征的发病相关。

文献复习：我们对相关文献进行了复习，发现COL4A4基因是导致Alport 综合征的主要致病基因之一。

该基因编码胶原蛋白α4链，该链在肾小球基底膜中起重要作用。

COL4A4基因突变可以导致胶原蛋白α4链的缺失或功能异常，从而破坏肾小球基底膜的稳定性，导致肾脏病变。

Alport综合征主要以遗传方式传播，有三种遗传模式，包括X连锁遗传、常染色体隐性遗传和常染色体显性遗传。

其中，COL4A4基因突变主要与常染色体显性遗传的Alport综合征相关。

结论：通过对一例Alport综合征患者的基因测序，我们发现其患有COL4A4基因新突变，进一步确认了该基因的致病性。

这一探究结果有助于增进我们对Alport综合征遗传机制的理解，并为该疾病的早期诊断和家族遗传咨询提供了重要的参考依据。

内科主治医师-29(总分100,考试时间90分钟)[A1/A2型题]1. 患者，男，30岁，浮肿、少尿1周，2周前有“感冒”史，BP：150/90mmHg，Hb80/L，尿蛋白(+++)，尿潜血(+++)，尿RBC15～20个/HP，血肌酐384μmol/L，B超左肾11.1cm×4.1cm×5.2cm，右肾12.2cm×4.8cm×5.4cm，下一步首选的方案是A. 抗炎治疗+血液透析B. 给予强的松龙冲击治疗+细胞毒类药物C. 给予强的松龙冲击治疗D. 肾穿后再定方案E. 先保守治疗，动态观察肾功能，根据情况再定2. 关于Goodpasture综合征，错误的是A. 有肺出血B. 抗肾小球基底膜抗体阳性C. 有肾小球肾炎D. 肾脏受累均表现为新月体性肾炎，因此预后差E. 抗肾小球基底膜抗体和ANCA可同时阳性3. Alport综合征是哪种纤维蛋白成分合成异常A. Ⅰ型胶原B. Ⅲ型胶原C. Ⅱ型胶原D. Ⅳ型胶原E. 层连蛋白4. 慢性肾炎的常见病理类型不包括A. 膜性肾病B. 系膜增生性肾小球肾炎C. 新月体肾小球肾炎D. 局灶性节段性肾小球硬化E. 系膜毛细血管性肾小球肾炎5. 慢性肾炎的综合治疗措施不应包括A. 常规应用糖皮质激素及细胞毒药物B. 积极控制高血压C. 肾功能不全氮质血症时限制蛋白和磷的摄入D. 避免用氨基糖苷类抗生素E. 避免不必要的造影检查6. 不支持Alport综合征的诊断的是A. 阳性家族史B. 肾组织电镜见GBM广泛变厚、撕裂C. 应用抗GBM Ⅳ型胶原α5链抗体做免疫病理检查，受累组织上不着色D. 临床上有肾脏病、眼病变及耳病变E. 肾功能急性、进行性损害7. 肾小球呈现线形免疫荧光的肾小球肾炎可能是A. 膜性肾病B. 新月体性肾小球肾炎C. 膜增生性肾小球肾炎D. 系膜增生性肾小球肾炎E. 毛细血管内增生性肾小球肾炎8. 好发于中老年的原发性肾病综合征的病理类型是A. 微小病变型肾病B. 系膜增生性肾小球肾炎C. 膜型肾病D. 系膜毛细血管性肾小球肾炎E. 局灶性节段性肾小球肾炎9. 患者，男，30岁，间断面部及双下肢浮肿3年。

JOURNAL OF RARE AND UNCOMMON DISEASES, APR. 2022,Vol.29, No.4, Total No.153Alport综合征的临床表现及诊疗进展*赵颖玲 于 力*广州市第一人民医院儿科 (广东 广州 510180)Clinical Manifestations and Progress of Diagnosis and Treatment of Alport Syndrome*ZHAO Ying-ling, YU Li *.Department of Pediatrics, Guangzhou First People’s Hospital, Guangzhou 510180, Guangdong Province, Chin a【第一作者】赵颖玲，女，主治医师，主要研究方向：小儿肾脏病与免疫性疾病。

E-mail：136****************·特约综述· Alport综合征(Alport syndrome，AS) 又称遗传性肾炎、遗传性进行性肾炎、家族性肾炎，是常见的遗传性肾小球疾病。

AS是由于COL4A3、COL4A4和COL4A5基因分别编码IV型胶原α3、α4和α5链的病理基因变异引起的[1-3]，发病率大概1/5000。

该病是一种多系统疾病，临床表现主要以肾脏损伤为主，表现为血尿、蛋白尿及进行性肾衰竭，多伴有神经性耳聋和眼部异常等，因此AS的医疗过程涉及多个学科(包括检查、诊断、治疗、遗传咨询)。

自1927年报道AS以来，医学研究人员孜孜不倦地利用各种科技手段探索其诊断和治疗。

尤其是近年来分子诊断技术的快速发展以及基因检测的容易获得，实现了对AS的精准诊断，同时AS的治疗研究也取得了一定进展。

因此，本文就AS的诊断与治疗进展进行综述。

1 AS的基因分型 根据遗传方式，AS分为X连锁Alport综合征(X-linked Alport syndrome，XLAS)、常染色体隐性Alport综合征(autosomal recessive Alport syndrome，ARAS)和常染色体显性Alport综合征(ADAS)。

[模拟] 呼吸科主治医师相关专业知识26一、以下每一道考题下面有A、B、C、D、E五个备选答案。

请从中选择一个最佳答案。

第1题：A.肥达反应B.抗HCV抗体检测C.血培养D.抗HIV抗体检测E.HBV标志物检测参考答案：D第2题：鉴别库欣综合征与单纯性肥胖，下述各项中最有意义的检查是A.糖耐量试验B.24h尿17-羟皮质类固醇C.24h尿游离皮质醇D.腹膜后充气造影见双侧肾影增大E.小剂量地塞米松抑制试验参考答案：E第3题：女性患者，56岁，糖尿病病史20年，一直用胰岛素治疗。

近3个月，颜面及双下肢水肿，并出现低血糖。

最可能的诊断是A.低蛋白血症B.黏液性水肿C.糖尿病肾病D.肝硬化E.慢性肾炎参考答案：C第4题：下列疾病不属于弥漫性结缔组织病的是A.类风湿关节炎B.炎症性肠病关节炎C.系统性红斑狼疮D.结节性多动脉炎E.白塞病参考答案：B第5题：自发性气胸的病因中在下列哪种情况中最为常见A.肺脓肿B.支气管肺癌C.慢阻肺疾病及肺结核D.支气管扩张E.胸膜上异位子宫内膜参考答案：C第6题：HBV具有高度传染性的指标应该是A.HBsAg(+)、抗-HBe(+)、抗-HBc(+)B.HBsAg(+)、抗-HBs(+)、抗-HBc(+)C.抗-HBs(+)、抗-HBe(+)、抗-HBc(+)D.HBsAg(+)、HBeAg(+)、HBV-DNA(-)E.HBsAg(+)、HBeAg(+)、HBV-DNA(+)参考答案：E第7题：风湿性疾病是指A.骨与软骨疾病B.自身免疫病C.胶原疾病D.累及关节及其周围组织的疾病E.韧带、肌腱及肌肉组织疾病参考答案：D第8题：女性患者，52岁，近5年采反复出现双手、腕及膝关节不适，伴不易控制的龋齿、牙齿脱落及腮腺反复肿大。

查体：球结膜充血；牙齿变黑，多数脱落，只留有残根；双手关节无明显肿胀、畸形。

首先考虑的诊断是A.干燥综合征B.白塞病C.骨关节炎D.银屑病关节炎E.痛风参考答案：A第9题：慢性萎缩性胃炎的主要病因是A.由急性萎缩性胃炎发展而来B.与长期饮酒有关C.与胆汁反流有关D.与自身免疫有关E.与长期吸烟有关参考答案：D第10题：下列哪种p受体阻滞药同时具有α受体阻滞作用A.普萘洛尔B.美托洛尔C.比索洛尔D.阿替洛尔E.卡维地洛参考答案：E第11题：伤寒患者经治疗后体温开始下降但未恢复正常，体温又再次上升，血培养阳性，属于A.再燃B.复发C.混合感染D.再感染E.重复感染参考答案：A第12题：肺性脑病与高血压脑病鉴别的主要依据是A.气短B.头痛C.高血压D.发绀E.昏迷参考答案：D第13题：女性患者，25岁，既往肺结核病史4年，经过规律治疗后，复查X线胸片示结核病灶已经好转。

临床AIPort综合征遗传性进行性肾炎临床表现、辅助检查及诊断A1POrt综合征称遗传性进行性肾炎，临床特点是血尿、蛋白尿及进行性肾功能减退，部分患者可合并感音神经性耳聋、眼部异常、食管平滑肌瘤等肾外表现。

临床表现血尿是AIPOrt综合征患者最常见的临床表现，为肾小球源性。

几乎Io0%的X1AIPOrt综合征和ARA1Port综合征患者具有镜下血尿。

62%的X1A1port 综合征男性患者、66%的ARA1port综合征患者有发作性肉眼血尿。

蛋白尿在疾病早期不出现或极微量，但随年龄增长出现并不断加重，甚至发展至大量蛋白尿。

终末期肾脏病。

X1AIPort综合征男性患者肾脏预后极差，近90%的患者在40岁之前发展至ESRD,而有18%的X1AIport综合征女性携带者在41岁后发生ESRD,对于ARA1port综合征患者，发生肾衰竭的中位年龄为22.5岁，常染色体显性遗传型AIPOrt综合征（ADAIPort综合征，OMIM104200）患者临床表现相对轻些。

感音神经性耳聋病变发生于耳蜗部位，最初累及高频区，故难以察觉，进行纯音测听才可发现，耳聋呈进行性加重，随年龄增长逐渐累及全音域，甚至影响日常对话交流。

X1A1Port综合征男性发生感音神经性耳聋较女性多，且症状严重。

眼部异常对A1port综合征具有诊断意义的眼部病变包括前圆锥形晶状体、黄斑周围点状和斑点状视网膜病变。

其中，黄斑周围斑点状视网膜病变较常见，需要用视网膜摄像的方法观察，病变通常不影响视力，但会随肾功能减退而进展；前圆锥形晶状体需借助眼科裂隙灯检查，可表现为进行性近视度数加深，病变和早期肾衰竭相关。

辅助检查1、实验室检查。

尿常规检查显示镜下血尿和蛋白尿。

肾功能检查提示血肌醉逐渐升高最终达到终末期肾病水平。

随肾功能恶化，还会伴发其他化验异常。

如血常规检查提示正细胞正色素性贫血，代谢性酸中毒及电解质异常，低血钙、高血磷、血甲状旁腺素水平升高等。

马凡氏综合征机制马凡氏综合征是一种先天性的遗传疾病，又称为马凡氏综合征、马凡综合征、马方综合征，属于一类罕见的多系统疾病。

它是由一个肺泡细胞发育异常引起的一系列结构和功能的缺陷所导致的，表现为多脏器受损，包括肺部、心血管系统、肾脏、骨骼和智力发育迟缓。

马凡氏综合征的发病机制尚不完全清楚，但通过研究已经有了一些了解。

马凡氏综合征是由于胚胎期发育异常导致的，具体来说是肺泡细胞的发育异常。

胚胎发育过程中，肺泡细胞应该逐渐发育成熟，并分泌肺泡表面活性物质以维持肺部的功能。

然而，在马凡氏综合征患者中，由于某种原因，肺泡细胞的发育过程中出现了问题，导致肺部功能的障碍。

目前研究发现，马凡氏综合征的发病与一个叫做FMR1基因的突变有关。

FMR1基因位于X染色体上，几乎每个人都拥有该基因，但正常情况下，FMR1基因的重复序列重复次数在普通范围内。

然而，在马凡氏综合征患者中，FMR1基因的重复序列重复次数明显增加，这导致了FMRP蛋白的产生不足。

FMRP蛋白是一种调控蛋白，它在神经细胞中的发育和功能中起到重要的作用。

FMRP蛋白的不足会导致神经细胞发育异常，并影响神经传递和连接的形成。

这在马凡氏综合征患者的脑部智力发育迟缓和行为问题中得到了验证。

同时，FMRP蛋白的不足也会影响其他器官的发育和功能。

具体来说，FMRP蛋白在肺部、心血管系统、肾脏和骨骼中都发挥了重要的作用，因此在马凡氏综合征患者中会出现这些器官的发育和功能缺陷。

此外，研究还发现，FMRP蛋白的不足还会导致神经细胞中突触可塑性的改变。

突触可塑性是神经细胞之间信息传递的重要机制，它使神经网络能够适应环境的改变并学习新的知识。

然而，在马凡氏综合征患者中，突触可塑性受到了影响，导致了记忆力和学习能力的下降。

综上所述，马凡氏综合征的发病机制主要与FMR1基因的突变和FMRP蛋白的不足有关。

FMRP蛋白的不足导致了肺泡细胞发育异常和其他器官的发育和功能缺陷，同时也影响了神经细胞的发育和突触可塑性。

内科主治医师肾内科学（专业知识）-试卷32(总分64,考试时间90分钟)1. A1型题1. 下面哪项不是以肾小管／间质损害为主要表现的遗传性肾脏疾病A. Bartter综合征B. Liddle综合征C. 薄基底膜肾病D. 家族性间质性肾炎E. 特发性Fanconi综合征2. 有关急性肾衰竭，下列哪项说法不正确A. 肾功能短期内迅速减退B. 肾小球滤过率下降C. 既往无慢性肾脏病史D. 有水、电解质、酸碱平衡紊乱E. 常伴有少尿3. 下述哪项指标提示患者是肾陛急性肾衰竭A. 尿比重＞1．018B. 尿渗透压＞500C. 尿钠浓度＜20D. 肾衰指数＜1E. 滤过钠分数＞14. 临床表现为突然无尿或间断无尿的肾功能不全患者，首先应考虑A. 肾前性氮质血症B. 肾小球疾病C. 肾后梗阻性疾病D. 急性肾小管坏死E. 急性间质性肾炎5. 应用BUN：Scr(mg／dl)比值鉴别肾前性氮质血症和急性肾小管坏死A. ＞20：1支持肾前性氮质血症B. ＞20：1支持急性肾小管坏死C. ＜20：1支持肾前性氮质血症D. ＞10：1支持肾前性氮质血症E. ＞1支持肾前性氮质血症6. 下列哪项肾血管疾病不引起急性肾功能衰竭A. 良性肾小动脉硬化症B. 溶血性毒综合征C. 恶性高血压D. 硬皮病肾危象E. 肾小动脉胆固醇结晶栓塞7. 肾前性急性肾衰尿沉渣镜检常见管型A. 红细胞管型B. 白细胞管型C. 棕色管型D. 透明管型E. 颗粒管型8. 下述哪项不是心排出量不足导致的循环血量下降引起的肾前性急性肾衰A. 心源性休克B. 充血性心力衰竭C. 肺栓塞D. 心包填塞E. 大量失血9. 肾皮质病变所致急性肾衰A. 肾小管上皮细胞肿胀，脂肪变性，基膜断裂，间质充血，水肿B. 肾小管内凝血及严重缺血，广泛肾小球小管坏死C. 肾间质中性粒细胞及嗜酸性粒细胞浸润，伴水肿D. 肾小球内细胞增生，纤维素样坏死，新月体形成E. 小叶问动脉纤维样坏死，间质水肿及白细胞浸润10. 急性肾衰竭的诊断依据是A. 电解质紊乱B. 尿液检查异常C. 贫血D. 血肌酐的绝对或相对值的变化E. 代谢性酸中毒11. 急性肾衰竭少尿期的表现是A. 高血钾症B. 高血钠症C. 高血钙症D. 高血磷症E. 高血脂症12. 下列哪项有助于急、慢性肾衰竭的鉴别A. 蛋白尿程度B. 血尿程度C. 高血压的程度D. 肾脏大小E. 酸中毒程度13. 急性肾衰竭患者每天应摄入的基本热量为A. 20～25kcal／kgB. 25～30kcal／kgC. 30～35kcal／kgD. 30～45kcal／kgE. 45～50kcal／kg14. 下列哪项有助于鉴别肾前性急性肾衰竭与急性肾小管坏死A. 氮质血症程度B. 尿钠浓度C. 尿量D. 肾脏影像学检查E. 血压降低的程度15. 急性肾衰竭时，下列哪种情况需紧急血液透析A. 血尿素氮＞20．4mmol／LB. 持续呕吐C. 血钾＞6．0mmol／LD. 急性肺水肿E. 动脉血气分析pH＜7．3516. 急性肾小管坏死的原因是A. 肾血浆流量下降B. 氨苄青霉素过敏C. 肾动脉及肾静脉栓塞等D. 急进性肾小球肾炎E. 前列腺增生肥大2. A2型题1. 男性，35岁，因体检时尿液检查发现蛋白尿(++)，红细胞0～5个／HP，颗粒管型0～1个／HP入院检查。