Upload
joy-cain
View
229
Download
0
Tags:
Embed Size (px)
Citation preview
CLINICAL BIOCHEMISTRY
Dr Shahida Mushtaq
OBJECTIVES provides advanced understanding and
applied knowledge in the theory and practice of Clinical Biochemistry
a critical understanding of how biochemical investigations are employed to develop a clinical diagnosis
Help you in developing necessary professional and research skills to promote lifelong learning and career development
COURSE CONTENTS:
Disorders of Protein Metabolism: Non-protein nitrogenous compounds (Urea, uric acid
& amino acids): Their normal plasma levels Disease states associated with their increased and
decreased levels in the plasma. Plasma Proteins:
Normal and abnormal levels of plasma proteins and diseases associated with increased and decreased levels.
Immunochemistry Components of the immune system. Diseases associated with disorders in the immune
system, multiple myeloma, systemic lupus erythromatosis, heavy-chain diseases, macroglobulinemia etc.
Clinical EnzymologyChanges in enzymatic activity in disease
states Hemoglobin
Normal and types of abnormal hemoglobins.Pathological cases associated with
abnormal hemoglobin, e.g., thalassemia, sickle cell anemia etc.
Disorders of Lipid MetabolismHyper and hypolipoproteinemia. Atherosclerosis & lipidoses.Fatty liver.
Disorders of Electrolytes, Blood Gases &Acid-base BalanceSodium, potassium, chloride & their
diagnostic value.Gas transport in the blood (Oxygen & CO2).Blood pH and its regulation.Acidosis and alkalosis (Metabolic and
respiratory) & Pathological conditions associated with each condition.
LAB WORK Estimation of serum enzymes:
LDH and its isoenzymes.CPK and its isoenzymes.
AldolaseLeucine aminopeptidase.Aspartate and Alanine Aminotransferases
AST and ALT. Serum glucose Lipid profile
REFERENCE BOOKS Clinical Biochemistry, 2nd Edition,
2008, R. Luxton.
INBORN ERRORS OF METABOLISM They arise from damaged gene leading
to an abnormal enzyme. They can affect many different
biochemical pathways. May be autosomal or sex linked. Mutation in gametes and normal cells.
IBEM They involve inheritance of abnormal
gene from one or both parents and are linked with abnormal enzyme leading to defect in metabolic pathway.
There may be defects in other types of proteins for example cystic fibrosis.
INBORN ERROR OF METABOLISM (IEM) About 1300 diseases known so far. About 100 start in the neonatal period About 20 are amenable to treatmentIncidence: rare
GENERAL ASPECTS OF (IEM) Suspect IEM in parallel to other
common conditions e.g. Sepsis. Non-specific signs and symptoms e.g.
poor feeding, lethargy, failure to thrive.
Majority of cases may be sporadic. Inborn errors of intoxication are
usually amenable to treatment.
A CLINICALLY USEFUL CLASSIFICATION
Group 1: Disorders that give rise to Intoxication
Group 2: Disorders involving energy metabolism.
Group 3: Disorders involving complex molecules.
(Proposed by JM Saudubray-2002)
GROUP 1: INTOXICATION TYPE
This group includes IEM that lead to acute or progressive intoxication from accumulation of toxic compounds proximal to metabolic block.
GROUP 1: INTOXICATION TYPE (CONT)
Includes: Aminoacidopathies e.g:
Phenylketoneuria (PKU)Maple Syrup Urine Disease (MSUD)Tyrosinaemia type I
Organic acidaemias e.g.Methylmalonic acidaemia (MMA)Propionic Acidaemia Isovaleric Acidaemia
GROUP 1: INTOXICATION TYPE (CONT)
Includes (Cont): Congenital Urea Cycle Defects
Arginosuccinate Lyase DefOrnithine Carbamyl Transferase Def
Sugar IntoleranceGalactosaemiaHereditary Fructose Intolerance
GROUP 2: DEFECTS IN ENEREGY METABOLISM
This group consists of IEM with symptoms due at least partly to a deficiency of energy production or utilization. They result from a defect in the: Liver Myocardium Brain Muscle
GROUP 2: DEFECTS IN ENEREGY METABOLISM (CONT)
Includes: Hypoglycaemic disorders
Gluconeogenesis defectsGlycogenosis defectsHyperinsulinism
Fatty Acid Oxidation Disorders
GROUP 2: DEFECTS IN ENEREGY METABOLISM (CONT)
Includes (Cont) Congenital Lactic Acidaemias
Pyruvate carboxylase deficiencyKrebs Citric Cycle defectsMitochondrial Respiratory Chain defects
GROUP 3: DISORDERS INVOLVING COMPLEX MOLECULES
This group includes diseases that involve defects in the synthesis or the catabolism of complex molecules.
These diseases are: Progressive Permanent Independent of intercurrent events Not amenable to treatment.
GROUP 3: DISORDERS INVOLVING COMPLEX MOLECULES(CONT)
Includes: Lysosomal Disorders Peroxisomal Disorders Golgi Apparatus Disorders Inborn Errors of Cholesterol Synthesis
INHERITANCE 23 pairs of chromosomes Autosomal or sex linked Homozygous or heterozygous inheritance pattern is different for both
autosomal or sex linked genes. Expression of gene depends on
dominence of genes.
INVESTIGATION OF IBEM
An accumulation of the sustrate before enzyme defect.
Decrease in amount of product of enzyme.
An increased concentration of alternate metabolism
A decrease or absence of enzyme activity
INVESTIGATION OF IBEM Screening for the IBEM in individuals
who do not have symptoms. Investigations of the patients with
symptoms of the IBEM.
SCREENING Detecting a patient with an IBEM even
before he shows overt symptoms of the disease
Screening should be done for high risk group
All newborn infantsFamily of affected childrenExpectant mothers who have previously
had affected children (pre natal diagnosis)
SCREENING OF NEWBORN INFANTS There is suitable treatment available for
the disease The disease is life threatening or
seriously debelitating The disease has relatively high
incidence A suitable test is available The cost is acceptable.
PHENYLKETONURIA AND CONGENITAL HYPOTHYROIDISM
INVESTIGATION OF SUSPECTED IBEM Infant may present with symptoms within few
days after birth or within few weeks of life. Failure to thrive Poor feeding Persistent vomiting Unexplained jaundice Unexplained hypoglycemia Ketosis Lactic acidosis Convulsions and coma Lethargy Hypotonia hyperventilation
FRONT LINE TESTS Plasma
ElectrolytesAcid base balanceBlood gasesGlucoseLFTCalcium
FOLLOW UP TEST Plasma
Insulin lactic acidAmmonia ketones
Urine Amino acidSugarOrganic acids
PRENATAL DIAGNOSIS Parents of the affected children Amniocentesis
Fibroblasts recovered from amniotic fluidCultured and specific enzyme studies are
performed 15th week should be completed by 20th week
CVS9th week complete within 10 daysDNA analysisCystic fibrosis