Introduction To Clinical Chemistry PDF 2025

Introduction to Clinical Chemistry PHS 4204  Clinical Chemistry Clinical chemistry is concerned with the analysis of body fluids to yield timely, relevant, accurate and precise information on the metabolic status of the human body.  Hospital Laboratories Anatomi...

Introduction to Clinical Chemistry PHS 4204  Clinical Chemistry Clinical chemistry is concerned with the analysis of body fluids to yield timely, relevant, accurate and precise information on the metabolic status of the human body.  Hospital Laboratories Anatomic Clinical Pathology & Laboratories Histopathology – Hematology – Surgical pathology Blood banking Surgicals Immunopathology Biopsies – Microbiology – Autopsy pathology – Clinical Chemistry Complete Special chemistry Incomplete Needle  Clinical diagnosis is essentially the interpretation of – relevant data obtained from the box – the process of separating signal from noise – and then giving the signal meaning- is it relative to the disease process we are looking for?  Throughout the world, hundreds of thousands of body fluid specimens are analyzed every day and the data obtained are interpreted and used in assessing the health of patients.  This is such a commonplace occurrence that we seldom stop to question it, or consider the implicit assumption that is being made: – that in vivo processes can be understood by analyzing their constituents in vitro.  In other words, that data obtained from a body fluid sample can be used to give us information about the status of the living organism from which it came.  This assumption is the cornerstone upon which clinical chemistry and related disciplines are based.  From the viewpoint of the clinical chemist, patients are ‘black boxes’, complex metabolic machines that process molecules to produce energy Considerable time, effort and money are expended in attempting to find out what is happening inside this box.  Friedrich Wöhler The conceptual chasm between in vivo processes and in vitro analysis, between life and the test tube, was not bridged until 1828 when Friedrich Wöhler (July 31, 1800 - September 23, 1882) synthesized urea in the absence of any ‘vital force’ or living organism.  Wöhler had discovered that urea could be produced by evaporating an isomeric solution of ammonium cyanate. This was the first ‘organic’synthesis, a milestone in clinical chemistry, a bridge between the ‘organic’ and ‘inorganic’ worlds, between the living body and the laboratory. This was the first proof that The complex processes occurring within the human body could be understood in terms of chemical procedures that could be carried out in vitro. This work removed the requirement for any mysterious ‘vital force’ that separated in vivo biochemistry from in vitro chemistry  Vital force Leading physiologists In the 19th century believed that processes within living organisms were unique and could not be duplicated in the laboratory.  Consequently, the in vitro synthesis of ‘organic’ compounds was believed to be impossible. It was postulated that living organisms contained a ‘vital force’ that was the very essence of life.  This dogma of a ‘vital force’ pervaded art and science. A ‘vital force’ (in this case ‘galvanic’) was required, to bring Frankenstein’s monster to life, in Mary Shelley’s (1797- 1851) proto- science fiction novel written in 1816  Vitalism held that no substance produced by living organisms could be synthesized by combining inanimate chemicals in a lifeless container in the laboratory.  To attempt such a synthesis was considered a futile task because of the absence of a ‘vital force’, an enabling factor present in all living things but absent from inanimate objects.  Sir Arthur Eddington (1882- 1944), was a leading proponent of Einstein’s theory of relativity. Despite his acceptance of Einstein’s revolutionary theory of space, time and gravity, Eddington believed firmly that living organisms possessed an unknown force above and beyond those explained by biochemists and physiologists.  One of the first to challenge the vitalists’ viewpoint was René Descartes (1596-1650) who proposed that animals were no more than ‘machines’. Descartes and other ‘mechanists’ believed that life could be explained fully by chemical and physical principles and properties alone.  In 1859 Charles Darwin’s (1809-1882) published the ‘Origin of Species’ with its implication that man could no longer be considered unique: that there was a continuity between man and the animals.  Darwinists argued that vitalism should join other theories of the universe, erroneous philosophies. Darwinists maintained that there is no difference between a living and a dead organism, which could not be explained in terms of chemistry.  Claude Bernard (1813-78) did not believe in ‘vitalism’ but neither did he agree fully with the ‘mechanists’. He believed that the hallmark of life was the presence of a‘definite idea’ which directed its development.  The pioneering clinical chemist, Henry Bence Jones (1813-73) believed that the vital force played a minor role in living processes and that most, if not all, living processes would eventually be understood in terms of chemical and physical laws.  Some adherents of vitalism attempted to minimize the significance of Wöhler’s discovery. For example, Johannes Müller (1801-58) argued that urea was not really an animal product after all, but was instead a product of excretion.  Charles Gerhardt (1816-56) took a similar stance, arguing that “... only the vital force operates to synthesize”. He maintained that urea was a decomposition product formed by purely chemical (non-vitalistic) forces and that this ‘decomposition’ was a type of in vivo combustion.  In 1853, Claude Bernard discovered that glycogen was formed by the liver. This contradicted yet another tenet of vitalism, i.e. that only plants could synthesize complex compounds which were subsequently consumed by animals. In 1860 Marcellin Berthelot (1827-1907) published a book that presented numerous examples of the synthesis of organic compounds from the elements. Hans Driesch (1867-1941) was perhaps the last of the ‘vitalists’, insisting that the functions of protoplasm could not be fully explained mechanistically.  Many components of biological materials that were considered outside the range of capability of the clinical chemistry laboratory and now assayed daily  The blood of patients receiving therapeutic drugs is analyzed regularly Even when concentrations are very low Toxicological sections of the clinical chemistry laboratory have developed extensively  Clinical Chemistry is a multidisciplinary field tht draws upon the fields of: – Pharmacology – Toxicology – Physiology – Immunology – Hematology Format of Clinical Chemistry Is designed to separate the large body of facts into three categories: – Laboratory techniques: The principles of analytical techniques – Pathophysiology: The ways in which the laboratory data is generated are related to disuse or organ dysfunction – Methods of analysis: In-depth survey of the measurement of commonly analyzed biochemical substances  To recognize erroneous analytical data the clinical chemist must have an understanding of pathophysiological mechanisms  Analyte The analyte (any substance that can be measured) can be discussed two ways: – 1. a discussion for instance on carbohydrates Or – 2. by clinical context – by disease or organ dysfunction  Clinical context A discussion of pathological conditions and their clinical symptoms Function and challenge tests that require laboratory analysis A correlation of analyte with disease state  Safety in the Clinical Laboratory Personal behavior Smoking, eating, and drinking should be prohibited in all work areas These activities should be carried out only in designated rest areas completely separated physically from work areas  The greatest danger form eating or smoking in the laboratory is the possibility of infection from laboratory specimens There is also the possibility that food or tobacco or other material could contaminate test materials  No matter what type of work is done (gloves or no) hands must be washed before leaving the lab  Carcinogenic hazard Many of the aromatic amines benzidines – for example used for the testing of hemoglobin both plasma hemoglobin, and occult blood has been replaced With proper precautions some potentially carcinogenic compounds can be used  With proper precautions some potentially carcinogenic compounds can be used occasionally Precautions should include: – Performing the procedure in an isolated area – In a good fume hood – Wearing rubber gloves – And a respirator if the material is a dust  Hepatitis The presence of hepatitis viruses in blood, tissue, urine and feces from infected individuals constitutes a hazard to laboratory personnel Samples from known (or suspected) hepatitis patients should be noticeably marked  Radioactivity All precautions concerning eating, drinking and smoking are particularly applicable to the radioisotope laboratory Although the amount of radioactivity associated with tests for radioimmunoassays is small it can still present a hazard  Radioisotopes often used for labeling are I125 and I131 If by chance these isotopes are injested the compounds may be broken down in the body and radioactive iodine absorbed and concentrated in the thyroid gland Thus the thyroid can receive a much larger dose of radiation that would be expected from a random distribution in the body  Microbiological hazards – All work done with potentially highly infectious specimens should be done in a clean air hood – If material is accidentally dropped, pour disinfectant over the contaminated area – cover with paper towels – Let stand for 30 minutes and then pick up with rubber gloves – The container must be autoclaved  Precautions for handling material (feces, blood, or any body fluid) likely to contain highly infectious agents – viruses, bacteria, fungi or parasites Should include covering all cuts or skin breaks with tape, wearing protective clothing and rubber gloves and working under a safety hood if possible Aerosol must be prevented Collection and Handling of Patient Specimens Quality control in the laboratory begins before the sample is collected from the patient. Accuracy arises from ensuring that the appropriate specimen is collected – The correct collection vessel is used – Pertinent collection variables are considered  Once the sample is collected and delivered to the laboratory errors may arise during the period before the analysis of the sample The problem of sampling collection and processing is complex No simple system meets all the requirements for all analytes that the clinical chemistry laboratory measures The one method of collection and storage for a particular analyte may be invalid for another  An awareness of the availability of many methods must be present It is also important to determine the type of specimens required for a particular analyte before one begins to obtain a specimen For example – the collection of urine for a toxic drug screen is appropriate whereas a serum sample is not  Types of Specimens Blood: – Is Connective Tissue – It is a suspension of cells in a protein-salt matrix – Cells include RBC (erythrocyte, corpuscle, red blood cell) WBC – Agranulocytes: lymphocytes and monocytes – Granulocytes: polymorphonuclear leucocyte, eosinophil, basophil Platelets  Plasma - The non-cellular portion of the blood contains proteins – some of which are involved in blood coagulation When the coagulation process is allowed to proceed to completion the non-cellular fluid which can be separated from the clotted material is called serum  Blood used for biochemical analysis is collected either from veins, arteries or capillaries For most testing the site of phlebotmy has no analytical or physiological significance Venous blood is used because of the ease of collection For a limited number of analytes, such as blood gases and lactic acid, significant differences arise between venous and arterial blood  Most testing is performed on the liquid or serum fraction of blood that has been allowed to clot The assumpttion is made that the distributionn of constituents between the cellular and extracelluar components of the blood is equal  One can extrapolate the concentration of an analyte in blood from that measured in serum is equal This assumption is usually valid for some analytes it is necessary to inhibit the blood clotting process using an anticoagulant Other analytes require the addition of a preservative for accurate results