Biomed Chem Lecture 1

Course Description

• BNUR 2015: A branch of biomedical and laboratory medicine.

• Focus on:

  • Structure of molecules and macromolecules

  • Various chemical processes and metabolic pathways within the body

  • Systemic approach of lab diagnostics

• Emphasizes:

  • Function tests of body systems in health and disease

  • Normal and abnormal biochemical lab findings

  • Interpretation of clinical and laboratory data

  • Role of laboratory in disease diagnosis

Lecture Outline

Introduction to Biomedical Chemistry and Laboratory Diagnostics

• Role of Laboratory Medicine in Patient Care

• Sample Types and Quality Assurance

• Normal Ranges/Variations

• Assessment of the Appropriateness of Test Results

Topics Covered

1. Organic Substrates: Proteins, Carbohydrates (CHO), Lipids, Nucleic Acid

2. Metabolic Pathways & Metabolic Regulation

Introduction to Laboratory Medicine

Patient Care Cycle Steps

1. Self-assessment of state of health

2. Interview & examination

3. Objective data collection

4. Role of the laboratory

5. Decision tree

6. Therapy & evaluation

Important Considerations

• Scope of Lab Services

• Goals of Lab Tests

• Types of Samples

• Quality Assurance

• Strategies to Assess the Appropriateness of Test Results

  • Accuracy & Precision

  • Reference Ranges, Critical Values, Variations

  • Sensitivity and Specificity of Tests

  • Right Test, Right Patient, Appropriate Time, Accurate Test Result

Scope of Lab Services

Subspecialties of Laboratory Medicine

• Hematology & Blood Banking

• Microbiology

• Cytology, Histology, & Histopathology

• Clinical Chemistry: e.g., Endocrinology, Immunology

Purpose of Study

• Early detection & diagnosis of disease

• Monitoring & evaluation of treatment

• Research studies

Goals for Laboratory Tests

Types of Laboratory Tests

• Diagnostic/follow-up tests

• Screening tests

• Point of care tests

Examples of Population-Disease-Lab Tests

• Neonates: Hypothyroidism, measured by Serum TSH

• Adolescents: Substance abuse, assessed via Drug screen

• Pregnancy: Gestational diabetes, evaluated through Plasma glucose

• Industry: Lead exposure, monitored via Blood lead

• Elderly: Malnutrition, checked using Serum vitamin D

Types of Samples

• Blood

  • Whole, plasma, or serum

• Urine

• Feces

• Cerebrospinal fluid (CSF)

• Renal stones

• Semen

• Others (with anticoagulants)

Data and Laboratory Management

• Important Components

  • Safety

  • Customer Service

  • Patient Preparation

  • Sample Collection

  • Sample Handling

  • Sample Transport

  • Quality Control

  • Record Keeping

  • Reporting

  • Personnel Competency Testing

  • Quality Assurance Cycle

Accuracy & Precision

Definitions

• Accuracy: Closeness of measurements to the true value. Determined by:

  • Comparing to a reference method

  • Comparing test results between laboratories

• Precision: Degree of fluctuation in measurements; determined by:

  • Internal Quality Control (QC)

  • Use of the same control over a specific time period

Physiological & Analytical Variation

Types of Variation

• Inter-individual Variation: Differences among individuals influenced by age, sex, race, etc.

• Intra-individual Variation: Variations within the same individual due to diurnal cycles, diet, and social factors.

• Reference Interval (RI): Normal variations of a value established statistically.

  • E.g., Sex differences for specific tests like CK, cholesterol, and thyroxine.

Mean, SD & CV

Statistical Definitions

• Mean (M): Average value of a dataset, calculated as
  $Mean = \frac{\text{sum of values}}{\text{number of variants (n)}}$

• Standard Deviation (SD): A measure of data dispersion relative to the mean.

• Standard Error of the Mean (SEM): $SEM = \frac{SD}{\sqrt{n}}$

• Coefficient of Variation (CV): The ratio of SD to the mean, expressed as a percentage; ideally < 5%.
  $CV = \frac{SD}{Mean} \times 100$

True & False Results

Test Classifications

• True Positive (TP): Correctly identifies a diseased patient.

• True Negative (TN): Correctly identifies a healthy individual.

• False Positive (FP): Incorrectly identifies a healthy individual as diseased.

• False Negative (FN): Incorrectly identifies a diseased individual as healthy.

Statistical Result Table

Predictive Values

Definitions

• Positive Predictive Value (PPV): Percentage of positive test results indicating presence of disease.
  $PPV = \frac{TP}{TP + FP} \times 100$

• Negative Predictive Value (NPV): Percentage of negative test results indicating absence of disease.
  $NPV = \frac{TN}{TN + FN} \times 100$

• Sensitivity: Percentage of diseased individuals with a positive test result.
  $Sensitivity = \frac{TP}{TP + FN} \times 100$

• Specificity: Percentage of healthy individuals with a negative test result.
  $Specificity = \frac{TN}{TN + FP} \times 100$

Critical Values

Definition

• Critical values used to guide quick clinical decisions.

Blood Glucose Critical Values

• Reference Interval: 70-110 mg/dL (3.8-6.1 mmol/L)

  • Critical Hypoglycemia: <40 mg/dL (2.2 mmol/L)

  • Critical Hyperglycemia: >450 mg/dL (25 mmol/L)

• Serum Calcium Critical Values:

  • Level 1: 2.10–2.62 mmol/L

  • Level 2: <1.75 mmol/L (Hypocalcemic tetany)

  • Level 3: >2.75 mmol/L (Primary hyperparathyroidism)

  • Level 4: >3.37 mmol/L (Hypercalcemic coma)

Incidence & Prevalence

Definitions

• Incidence: Number of new cases in a population within a specified time frame (e.g., per year).

• Prevalence: Total number of cases present in a population at a specific point in time.

Organic Substrates

Proteins

• Most abundant organic molecules (>15% of cellular structure)

• Body synthesizes 100,000 to 140,000 types of proteins

  • Each has different structure and function

• Composed of elements: Carbon (C), Oxygen (O), Hydrogen (H), Nitrogen (N), and Sulfur (S).

• Structural Units: Amino Acids (AA)

Functions of Proteins

• Structure: E.g., Collagen (included in hair and nails).

• Transport: E.g., Hemoglobin transports oxygen.

• Storage: E.g., Myoglobin stores oxygen.

• Signal Transduction: E.g., Receptors transmit signals.

• Hormones: E.g., Insulin regulates blood sugar levels.

• Catalysis: Enzymes facilitate biochemical reactions.

Amino Acids (AA)

• Essential Amino Acids: Nine essential AA must be sourced through the diet.

• Each AA has:

  • An amino group (NH2), a carboxyl group (COOH) and a variable R group.

  • Two ends: N-terminal and C-terminal.

  • Charges can be positive (basic), negative (acidic) or neutral.

Structural Levels of Proteins

1. Primary Structure: Sequence of amino acids.

2. Secondary Structure: A-helix or B-sheet formations.

3. Tertiary Structure: Overall 3-D shape of the protein.

4. Quaternary Structure: Complex of multiple polypeptides.

Denaturation of Proteins

• Loss of the normal 3D structure, rendering them biologically inactive.

• Can be physiological (e.g., as part of metabolic processes) or pathological (caused by heat, shear forces, chemicals).

Carbohydrates

Types of Carbohydrates

• Monosaccharides:

  • Pentose sugars (5C) are part of RNA & DNA (e.g., ribose).

  • Hexose sugars (6C) are energy sources (e.g., glucose, fructose, galactose).

• Disaccharides: Formed from two linked monosaccharides (e.g., sucrose, lactose).

• Polysaccharides: Long chains of monosaccharides, e.g., cellulose and glycogen, serving as energy sources.

Carbohydrate Structure

• Composed of C, H, O with a 1:2:1 ratio.

• Examples include structural formulas for glucose, fructose, and galactose.

Lipids

Types of Lipids

• Fatty Acids (FA): Can be saturated or unsaturated.

• Glycerides:

  • Monoglycerides, diglycerides, triglycerides.

• Nonglycerides: Phospholipids and sterols.

• Combinations: Glycolipids and lipoproteins.

Lipid Characteristics

• Hydrocarbon-containing compounds, hydrophobic.

• Essential for cell structure and function, extracted using organic solvents.

Fatty Acids

• Precursor components of lipids.

• Long chains of carbon atoms with COOH group.

  • Saturated (single bonds)

  • Unsaturated (one or more double bonds, can be cis or trans).

Glycerides

• Composed of glycerol and fatty acids bonded through ester bonds.

Phospholipids

• Form cell membranes, consisting of glycerol, two fatty acids, and a phosphate group; contains a hydrophilic head and hydrophobic tail.

Nucleic Acids

Types

• Deoxyribonucleic Acid (DNA): Carries genetic information, found in nucleus and mitochondria.

• Ribonucleic Acid (RNA): Involved in protein synthesis; includes mRNA, tRNA, and rRNA.

Structure of DNA

• Composed of nucleotides, with deoxyribose sugar, phosphate group, and nitrogen bases (A, T, C, G).

• Forms the base-pairing rule (A-T, C-G).

• Antiparallel double-helix structure.

Genetic Code

• Represents chemical language for DNA instructions using base sequences, forming a triplet code where three bases equal one amino acid.

Metabolic Pathways & Regulation

Metabolism

• Refers to all biochemical reactions in an organism.

• Anabolism: Building molecules, requiring energy.

• Catabolism: Breaking down molecules, producing energy.

Cellular Metabolic Processes

• ATP Generation and utilization, energy balance, and the roles of macromolecules.

  • Specific metabolic pathways (e.g., glycolysis, TCA cycle) occur in distinct cellular compartments.

Metabolic Pathway Relationships

• Interconnected systems whereby substrates convert into products; includes glycolysis, gluconeogenesis, fat metabolism, etc.