BY3BC1- Medical Biochemistry Lecture 1 - Organ Function Testing LO- - How do biomedical scientists use biochemical test? - How do we identify abnormal results? - How good is a particular test at providing a diagnosis? Uses of biochemical tests - Diagnosis (HIV number of virus particles can diagnose HIV) - Management - Progression of disease (quantify viral load and see how its reducing due to treatment if it is) - Response of treatment - Recurrence of disease (can track viral load months after treatment) - Screening -detection in asymptomatic individuals - Population -new-born screening - Selected group- obese patients for type 2 diabetes mellitus - Individual - familial hypercholesterolaemia Biomarkers - Biochemical tests use biomarkers (biomarker natural occurring molecule/gene/chrematistic in which a particular pathogenic disease/pathway can be identified) - Usually measured in blood but can be in urine, faeces, or CSF (found in the brain and spinal cord- difficult to retrieve, taken from lower region of the spine if needed) - Biomarkers can be enzymes, metabolites (when a disease specifically alters a biological mechanism) or hormones (e.g. insulin in diabetes I, individuals who have extra growth hormones acromegaly) - Ions or gases are often also measured in clinical biochemistry Tissue Blood Enzyme - Serum proteins/ enzymes as biomarkers Enzyme
- In normal tissue the cell membrane is intact, and enzyme escapes due to normal cell turnover - When the membrane is damaged high levels of enzyme are released into the blood. The enzyme in the blood can diagnose which disease caused the damage. - Are there any problems with this approach? - Increased cell number increases serum enzyme activity (leads to false increase) in natural circumstances - Introduction of enzyme within a tissue increases release (too much alcohol, increases alcohol dehydrogenase- but isn't due to disease due to a stimuli) Tissue - Increased serum enzyme activity does not always mean cell damage Enzyme - May be hyper-proliferation (due to a drug or cancer (cancers arent indicitive of the enzyme released)) Enzyme Enzyme - May be induction (synthesis of more enzyme) - Some instances of induction can be diagnostically useful - Same argument applies to non-enzyme proteins in the serum e.g. albumin - Many of these are normally secreted Enzyme what makes an ideal biomarker? - Tissue specific (i.e. only present within one tissue) - Rapid release in response to damage (heart attack needs to know urgently) - Very low in serum of normal individuals (biomarkers levels need to stay high in conc when disease occurs and low in normal conditions) - Easily measures with clear universal reference values - If these criteria are difficult to achieve use a battery of tests to make a profile - (e.g heart attack you do a ECG, blood pressure reading, blood test looking for troponin) Blood Metabolites as biomarkers - Useful to assess the function of the organ that produces them - However, many metabolites are not 'organ specific' - The concentration in serum may depend on uptake by other tissues and/or excretion