Transcript Clinical biochemistry - ASAB-NUST | Lectures for ASAB , UG

Clinical chemistry, chemical pathology
and medical biochemistry
 is the area of clinical pathology that is
generally concerned with analysis of
bodily fluids.
 Originated in the 19th century with simple
chemistry test of blood and urine

Disorders of Protein Metabolism:
 Non-protein nitrogenous compounds (Urea,
uric acid & amino acids): 3 lectures

› 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, heavychain diseases, macroglobulinemia etc.

Clinical Enzymology
› Changes 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 Metabolism
› Hyper and hypolipoproteinemia.
› Atherosclerosis & lipidoses.
› Fatty liver

Disorders of Electrolytes, Blood Gases &Acidbase Balance
› Sodium, 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.

Blood analysis:
› Electrophoretic separation of plasma proteins.
› Electrophoretic separation of plasma lipoproteins.

Estimation of serum enzymes:
› LDH and its isoenzymes.
› CPK and its isoenzymes.

Ornithine carbamoyl transferase.
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
5-nucleotidase.
Isocitric dehydrogenase.
Sorbitol dehydrogenase.
Glucose-6-P dehydrogenase.
Aldolase
› Leucine aminopeptidase.
› Aspartate and Alanine Aminotransferases AST and
ALT.
 Serum
electrolytes:
› Chloride sodium, Potassium, Calcium,
Magnesium, Phosphorus.
 Urine
Analysis:
› Porphyrins.
› Urobilinogen, Amino Levulinic Acid (ALA)

Clinical Biochemistry, 2nd Edition, 2008, R.
Luxton.

Clinical Biochemistry made ridiculously
simple, 2010, Stephen Goldberg.

Clinical Biochemistry; An illustrated color
text, 2008, Allan Gaw, Michael J. Murphy,
Robert A.
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)

This group includes IEM that lead
to acute or progressive
intoxication from accumulation
of toxic compounds proximal to
metabolic block.
Includes (Cont):
 Congenital Urea Cycle Defects
› Arginosuccinate Lyase Def
› Ornithine Carbamyl Transferase Def

Sugar Intolerance
› Galactosaemia
› Hereditary Fructose Intolerance
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
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
Includes:
 Hypoglycaemic disorders
› Gluconeogenesis defects
› Glycogenosis defects
› Hyperinsulinism

Fatty Acid Oxidation Disorders
Includes (Cont)
 Congenital Lactic Acidaemias
› Pyruvate carboxylase deficiency
› Krebs Citric Cycle defects
› Mitochondrial Respiratory Chain defects
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.
Includes:
 Lysosomal Disorders
 Peroxisomal Disorders
 Golgi Apparatus Disorders
 Inborn Errors of Cholesterol Synthesis

Carbohydrate metabolism
› Glycogen storage diseases
› Galactosemia
› Hereditary fructose intolerance

various
galactose-1-phosphate uridyle
transferase, galactose kinase
fructose bisphosphate aldolase
Amino acid metabolism
› Phenylketonuria
› Alkaptonuria
› Maple syrup urine disease
phenylalanine hydroxylase
homogentisic acid oxidase
branched chain ketoacid hydroxylase

Lipid metabolism
› Hyper and hypo lipoproteinemia

Steroid metabolism
› Congenital adrenal hyperplasia

various
21-hydroxylase
Purine metabolism
› Gout
various
› Lesch-Nyhan syndrome
HGPRT
(hypoxanthine-guanine phosphoribosyl transferase)

Lysosomal storage disease
› Tay-sachs disease……..
› Gaucher’s disease……..

hexosaminidase A
glycosylceramidase
Cell transport defects
› Cystinuria……….
› Renal glycosuria……….
› Renal tubular acidosis….
amino acid transport
glucose transport
hydrogen ion
transport
 About
5 million children die in
the first month of life in
developing countries
 Four million children are born
with some congenital
anomaly.
WHO
 Almost
27 - 30 % of babies dying
of SIDS are now proved to be
having some Inborn Errors of
Metabolism (IEM).
 About 5 to 15 % of all sick
neonates in NICU are expected
to have some IEM
WHO

a single gene defect causes
a clinically significant block in a
metabolic pathway resulting either in
accumulation of substrate behind the
block or deficiency of the product
IEM arises from a damaged gene which
leads to abnormal enzyme.
 May be autosomal or sex-linked.
 May be recessive or dominant in
expression.
 Heterozygote will have both normal and
abnormal alleles. But homozygote will
have two alleles the same on each
chromosome.

An accumulation of the substrate before the enzyme
defect*.
 A decrease in the amount of the product is observed.
 An increased concentration of the alternative
metabolites*.
 A decrease or absence of the enzyme activity.

Screening for IEM who do not have the
symptoms
 Investigations of the patient with
symptoms of the IEM

May be carried out in three stages:
a. Diagnosis of Broad Category: Saudubray
et al (2002)* suggested a battery of simple
and routine tests for identification of the
broad category of the disorders. These tests
include plasma electrolytes, ABGs, blood
ammonia and lactic acid etc.
*Saudubray JM, Nasoogne MC, Lonlay PD, Touati G. Clinical approach to
inherited metabolic disorders in neonates: an overview. Smin Neonatol 2002; 7: 3-15.
May be carried out in three stages:
b. Diagnosis of the exact disorder
• It requires very sophisticated equipment
e.g. HPLC, tandem mass spectrometry,
GC-MS and ion exchange
chromatography.
May be carried out in three stages:
b. Diagnosis of the exact disorder (cont)
• These techniques also require elaborate
infrastructure of trained manpower,
proper back-up service for the
instruments and regular supply of
reagents.
May be carried out in three stages:
b. Diagnosis of the exact disorder (cont)
• AKU hospital has taken an initiative to
establish the first-ever lab in the country
for the pin-point diagnosis of some of the
IEM.
May be carried out in three stages:
c. Determination of deficient enzyme or
protein Although a few laboratories in the
world provide this facility, this is only of
academic and research interest. Diagnosis of
the genetic defect provides another
promising pathway for some of these
disorders.