dr shahida mushtaq. provides advanced understanding and applied knowledge in the theory and...

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