医检-专业英语总.doc

Medical English for laboratory medical students Department of Laboratory Medicine 0 Medical English for laboratory medical students Department of Laboratory Medicine 1 contents Chapter 1 Disorders of Lipoprotein metabolism 1 Chapter 2 Diagnosis of Liver Disease 7 Chapter 3 Introduction to Quality Control Techniques 13 Chapter 4 Clinical Approach to Bleeding Disorders 20 Chapter 5 Automated Blood Cell Counter Principles 33 Chapter 6 Transfusion Biology and Therapy 41 Chapter 7 Complement in Disease States 58 Chapter 8 Clinical and Laboratory Evaluation of Systemic Rheumatic Diseases 63 Chapter 9 Introduction to Microbial Diseases 70 Chapter 10 Gram Positive Cocci 75 Chapter 11 Gram Negative Bacteremia 80 Chapter 12 Molecular Pathology An introduction 84 Chapter 13 Molecular pathology of infectious diseases 91 Chapter 14 Therapeutic Drug Monitoring 99 Chapter 15 Toxicology 116 Chapter 16 Laboratory Tests in Diagnosisand Management of Diabetes Mellitus 126 Chapter 17 Thyroid function tests 134 Medical English for laboratory medical students Department of Laboratory Medicine 2 Chapter 1 Disorders of Lipoprotein metabolism DISORDERS OF THE EXOGENOUS LIPOPROTEIN PATHWAY The term exogenous lipoprotein pathway refers to the metabolism of intestinal lipoproteins primarily those formed in response to dietary fat i e chylomicrons Genetic defects in either lipoprotein lipase LPL or apoC 11 and lead to significant hyperchylomicronemia and hypertriglyceridemia Brunzell 1989 Defective or Missing LPL This genetic condition is ordinarily accompanied by massive increases in chylomicrons with marked hypertriglyceridemia as high as 10 000 mg dL The marked chylomicronemia indicative of an inability to clear dietary fat is manifested by a thick creamy layer over a clear infranate in a tube of plasma left to stand overnight at 4 Type I pattern Hypercholesterolemia is normally present but the ratio of triglyceride to cholesterol is usually 10 or higher VLDL cholesterol is normal but HDL cholesterol and LDL cholesterol levels are low In individuals with functional LPL the intravenous injection of heparin releases membrane bound LPL into the bloodstream this is called the post heparin lipolytic activity test or PHLA test PHLA is absent from the plasma of affected patients and also from adipose tissue when tested The cofactor for LPL apoC II is present in normal concentrations however This pediatric disorder ordinarily presents before the age of 10 years Abdominal pain is usually the initial symptom presenting as colic in the first year of life or as an acute abdominal condition later in childhood Other clinical features may include eruptive xanthomas hepatosplenomegaly and lipemia retinalis The absence of atherosclerosis in LPL deficiencies suggests that chylomicrons unlike chylomicron remnants are not atherogenic This disorder is rare and is due to the homozygous state for a mutant allele The human LPL gene is approximately 30 Kb in length and consists of 10 exons interrupted by nine introns Missense mutations typically predominate in the LPL gene with a preferential location in exons 3 Medical English for laboratory medical students Department of Laboratory Medicine 3 4 and 5 mutations have been described in the catalytic triad Asp158 His241 and Ser132 Brunzell 1989 Once the mutation has been elucidated in the affected proband the DNA from the members of these rare families can be screened for a similar mutation Parents or siblings who are obligate heterozygous carriers for the defect in the LPL gene can have mild dyslipidemia which can present as hypercholesterolemia alone hypertriglyceridemia alone or both lipids elevated an isolated low HDL cholesterol level has also been described The pleiotropic presentation in obligate heterozygous carriers for LPL deficiency led to the hypothesis that such patients may reflect a subset of familial combined hyperlipidemia FCHL Kwiterovich 1993a Deficiency of ApoC II When apoC II the cofactor for LPL is deficient hypertriglyceridemia can vary from 800 to almost 10 000 mg dL A massive increase of chylomicrons alone may occur or can also be accompanied by an increase in VLDL see later Cholesterol levels range from approximately 150 to 1000mg dL LDL cholesterol and HDL cholesterol levels are below the fifth percentile for normal individuals PHLA activity is absent or very low However addition of apoC II to plasma of these patients in vitro or by blood or plasma transfusion in vivo allows normal PHLA activity ApoC II levels when measured immunochemically are present in only trace amounts The problem usually presents in adulthood with pancreatitis although one patient developed pancreatitis as early as age six The disorder is rare and inherited as an autosomal recessive trait A number of abnormalities in ApoC II have been described They are usually caused by either small deletions or a splice site mutation Breslow 1989 Brunzell 1989 l DISORDERS OF THE ENDOGENOUS LIPOPROTEIN PATHWAY The endogenous lipoprotein pathway refers to lipoproteins and apolipoproteins that are synthesized in tissues other than the intestine predominantly in the liver Genetic defects have been described at various points along the VLDL endogenous lipoprotein pathway IDL endogenous lipoprotein pathway and VLDL endogenous lipoprotein pathway Such defects are primarily related to 1 increased hepatic production of apoB 100 leading to group of closely related syndromes of VLDL apoB overproduction 2 increased synthesis of VDDL or 3 catabolic defects in the removal of LDL either through the defect in the Medical English for laboratory medical students Department of Laboratory Medicine 4 LDL receptor itself or a defect in the ligand for the LDL receptor namely apoB 100 Familial Combined Hyperlipidemia FCHL One of the first disorders of VLDL apoB overproduction was described in families of survivors of premature myocardial infarction K witerovich 1993a Overproduction of apolipoprotein B and VLDL lead to the overproduction of VLDL remnants IDL and LDL Kane and Havel 1989 Depending on the activity of LPL the patient may present with an elevated level of VLDL alone Type IV lipoprotein phenotype an elevated level of LDL alone Type a lipoprotein phenotype or an elevated level of both VLDL and LDL Type b lipoprotein phenotype Tendon and tuberous xanthomas are not part of the clinical presentation of FCHL although corneal arcus vertical ear creases and isolated xanthelasma can be This disorder is probably inherited as an autosomal dominant trait and ordinarily the diagnosis is made by finding at least on first degree relative who has a lipoprotein phenotype distinctly different from the proband Expression of the disorder is delayed but it is not unusual to see FCHL or one of its metabolic variants presenting in children and adolescents from families with premature CHD Cortner 1990 Other variants of FCHL which are also characterized by the presence of small dense LDL particles include hyperapobetalipoproteinemia hyperapoB LDL subclass pattern B familial dyslipidemic hypertension and syndrome X Kwiterovich 1993a In addition to small dense LDL particles these syndromes tend to share other characteristics such as hyperinsulinism glucose intolerance and adult onset diabetes mellitus Hypertension and low levels of HDL Particularly when hypertriglyceridemia is part of the phenotype The genetic defects underlying FCHL are not known but FCHL is undoubtedly genetically heterogeneous A number of candidate genes for FCHL and its related syndromes have been proposed These include defects in the regulatory or structural portion of the APOB gene although evidence from three laboratories indicates that a defect in this gene is highly unlikely as a common etiology of FCHL the trans DNA binding protein for APOB heterozygous carriers for a defect in the LPL gene although recent data indicate that this is unlikely to be a common cause of FCHL the APOA I C III A IV gene complex e g increased levels of apoC III may inhibit lipolysis or a defect in apoA IV may interfere with its proposed role in facilitating the transfer of apoC II to chylomicrons the ATHS gene on chromosome 19 the insulin receptor gene the gene for the putative basic protein receptor and mutations in the genes for several basic serum proteins that play a role in cellular lipid acylation Kwiterovich 1993a Several laboratories have shown evidence that there is a cellular defect in cultured fibroblasts Medical English for laboratory medical students Department of Laboratory Medicine 5 from patients with hyper apo B to the normal response to serum basic proteins I and II on the production of cellular hyper apo B to the normal response to serum basic proteins I and II on the production of cellular triglyceride and cholesterylesters respectively Kwiterovich 1993a Overproduction of Triglyceride Enriched VLDL In some patients with endogenous hypertriglyceridemia Hepatic triglycerides are oversynthesized but apoB is not leading to the secretion of triglyceride enriched VLDL Kane 1989 Such patients usually present with hypertriglyceridemia and low levels of LDL cholesterol and HDL cholesterol The disorder is believed to be due to the inability of LDL cholesterol and HDL cholesterol The disorder is believed to be due to the inability of LPL to hydrolyze normally such large triglyceride enriched VLDL In contrast with FCHL such patients and their affected family relatives do not have elevations in LDL and treatment of such familial hypertriglyceridemic patients FHTs with diet weight loss and medication will not produce a flip flop pattern with a conversion from a Type IV to a Type IIa or Type IIb pattern as can occur in FCHL CAD appears less prevalent in such patients compared with patients with Type IV lipoprotein patterns from FCHL families in whom the Type IV pattern is often accompanied by above average levels of LDL cholesterol and significant elevations in LDL apoB In families in whom FHT breeds true the adults often have glucose intolerance obesity hyperuricemia and peripheral vascular disease This disorder is probably inherited as an autosomal dominant trait with reduced penetrance in that the phenotype is expressed in only one of five children under the age of 20 years born to an affected parent Familial Hypercholesterolemia Familial hypercholesterolemia FH is an autosomal dominantly inherited condition that has a gene dosage effect Hobbs 1992 FH heterozygotes have plasma concentrations of total and LDL cholesterol that are elevated two to three times above normal FH homozygotes have levels that are elevated by five to six times FH is completely expressed at birth and early in childhood and the frequency of FH heterozygostes is about 1 in 500 Kwiterovich 1993b The triglyceride and HDL cholesterol levels are often normal in FH heterozygotes but persons with FH can have modest hypertriglyceridemia and a lower HDL cholesterol level The heterozygous FH child is clinically asymptomatic in the first decade of life 10 to 15 of these children develop tendon xanthomas during the second decade of life most commonly in the Achilles tendon and extensor tendons of the hands K witerovich 1993b However children with heterozygous FH manifest endothelial cell dysfunction in the first decade of life Celemajer Medical English for laboratory medical students Department of Laboratory Medicine 6 1992 CAD is present in about 20 of males by age 40 and in 50 by age 50 such early CAD is delayed 10 years in females with heterozygous FH Homozygous FH children have cholesterol levels that range from 600 to 1000mg dL Planar xanthomas flat orange colored skin lesions may be present at birth and usually occur by five years of age Planar xanthomas can be found on the buttocks between the webbings of the fingers and in the popliteal fossa Tendon and tuberous xanthomas often develop between the ages of 5 and 15 years Angina pectoris and myocardial infarction are common in the second decade of life and have occurred as early as six years of age Generalized atheroclerosis affects the aortic valve and the aorta leading to aortic stenosis that is often life threatening The fundamental defect in FH has been elegantly elaborated by Goldstein Browm and coworkers Hobbs 1992 Over 150 genetic mutations have been described in the locus that specifies the LDL receptor gene include insertions deletions missense and nonsense mutations The synthesis intracellular transport clustering in coated pits on the cell surface ability to bind and internalized LDL and recycling of the LDL receptor can each be affected by a mutation in the LDL receptor gene A number of patients with the clinical phenotype of homozygous FH are true genetic compounds that is they have two different mutant alleles at the LDL receptor locus that results in nonfunctional or markedly defective LDL receptors Familial Defective ApoB 100 In 1 of about 20 families the presence of high LDL cholesterol levels and xanthomas is not due to FH LDL receptor activity is normal but a defect in the ligand apoB is present in which glutamine is substituted for arginine at residue 3500 Myant 1991 The mutant apoB in this disorder familial defective apoB 100 is not bound normally by the LDL receptor often leading to elevated LDL cholesterol levels However most patients with familial defective apoB 100 do not have tendon xanthomas and the LDL cholesterol levels in children or adults with this disorder can be normal or moderately elevated Myant 1991 The defect appears to account for only a small proportion perhaps 1 to 2 of premature CAD For the purpose of treatment it does not appear necessary to distinguish FH from familial defective apoB 100 Medical English for laboratory medical students Department of Laboratory Medicine 7 New Words and Phrases Chylomicrons 乳糜微粒 Hyperchylomicronemia 高乳糜微粒血症 Hypertriglyceridemia 高甘油三酯血症 Intravenous 静脉内的 Lipolytic 脂分解的 Xanthomas 黄色瘤 Hepatosplenomegaly 肝脾肿大 Atherosclerosis 动脉粥样硬化 Dyslipidemia 脂代谢紊乱 Hypercholesterolemia 高胆固醇血症 Pancreatitis 胰腺炎 Autosomal 常染色体 Apolipoproteins 载脂蛋白 Ligand 配体 Hyperlipidemia 高脂血症 Xanthelasma 黄斑瘤 Hypertension 高血压 Hyperuricemia 高尿酸血症 Medical English for laboratory medical students Department of Laboratory Medicine 8 Chapter 2 Diagnosis of Liver Disease In this section the major hepatic disorders are discussed with emphasis on laboratory evaluations that enable diagnosis often without the need to perform invasive procedures such as liver biopsies It is important to remember that in acute hepatitis the principal changes are significant elevations of aminotransferases in cirrhosis these tend to remain normal or become slightly elevated while the total protein and albumin are depressed and ammonia concentrations in serum are elevated In post hepatic biliary obstruction bilirubin and ALP become elevated and in space occupying diseases of the liver ALP and LD are elevated In fulminant hepatic failure the aminotransferases and ammonia are elevated while total protein and albumin are depressed HEPATITIS Hepatitis usually first manifests itself clinically with the symptoms of fatigue and anorexia Jaundice may be present Generally jaundice is first seen as clear icterus when the patient has total serum bilirubin concentrations above 2 mg dL The cause of acute of acute hepatitis is almost always viral although chemical exposure such as to carbon tetrachloride or chloroform or to drugs such as acetaminophen especially in children should be considered A special category of toxin induced hepatitis is that induced by alcohol discussed subsequently The cardinal finding in hepatitis is a rise in the aminotransferases to values of more than 200IU L and often to 500 or even 1000 IU L The AST ALT ratio is close to 1 or may slightly favor ALT The bilirubin is invariably elevated and is composed of both direct and indirect types Elevations of indirect bilirubin are due to the inability of injured hepatocytes to conjugate bilirubin whereas the rise of direct bilirubin is due to the blockage of compromised canaliculi secondary to the inflammatory process that occurs in the acute phase Because of hepatocyte damage LD levels are mildly elevated to values of 300 to 500 IU L Because of inflammation of canaliculi and Medical English for laboratory medical students Department of Laboratory Medicine 9 ductules necrosis of canaliculi and ductules or both the ALP is often also elevated to values of 200 to 500IU L Unless the hepatitis is severe and involves the whole liver progressing to fulminant hepatic failure the total protein and albumin are within their normal ranges The globulin fractions may be elevated as a result of infection Given the pattern of the analytes suggestive of hepatitis specific causes should be screened for i e a determination of serologic markers for hepatitis A B and C Screening for anti hepatitis A IgM and for HBsAg can be performed within one day If either of these tests is positive the diagnosis is established If they are negative further screening for hepatitis B should be undertaken i e determination of serum titers of anti HBcAg IgM and IgG core window and anti HbsAg IgG If only the latter screen is positive it may be difficult to establish whether hepatitis B is the cause of the infection or whether the patient has been exposed to the virus in the past Unless the patient has chronic active or persistent hepatitis in which case HBsAg is continuously present titers of anti HBsAg IgG are elevated long after the aminotransferases return to normal levels If hepatitis B can be ruled out screening for antibodies to hepatitis C should be performed If this screen is negative other viral causes should be sought e g CMV and EBV Other causes such as chemical toxins should also be considered especially when a viral hepatitis screen is negative In alcoholic hepatitis the described pattern of abnormal analyte concentrations holds except that AST often becomes disproportionately elevated over ALT In addi