Medical Interventions End of Course Comprehensive Study Guide

Overview of Medical Interventions and Examination Structure

• Medical interventions are measures used to improve health or alter the course of an illness. They function to maintain health and homeostasis within the body.

• Primary categories of medical interventions include:

  • Genetics

  • Pharmacology

  • Diagnostics

  • Surgery

  • Immunology

  • Medical Devices

  • Rehabilitation

• The Medical Interventions (MI) End of Course (EOC) Exam consists of a total of $49$ Multiple Choice (MC) items.

• The approximate weight of each unit on the exam is as follows:

  • Unit 1.1: $11\%$

  • Unit 1.2: $7\%$

  • Unit 1.3: $7\%$

  • Unit 1.4: $8\%$

  • Unit 2.1: $8\%$

  • Unit 2.2: $6\%$

  • Unit 3.1: $8\%$

  • Unit 3.2: $7\%$

  • Unit 3.3: $8\%$

  • Unit 3.4: $7\%$

  • Unit 4.1: $12\%$

  • Unit 4.2: $5\%$

  • Unit 4.3: $3\%$

  • Unit 4.4: $3\%$

Information Gathering, Disease Identification, and Bioinformatics

• Signs vs. Symptoms:

  • Signs are objective, measurable, and recorded by healthcare professionals (e.g., temperature, heart rate, blood pressure, rash, swollen glands).

  • Symptoms are subjective problems reported by the patient (e.g., tiredness, sore throat, nausea).

• Outbreak Investigation: Finding "Patient 0" (the first person infected) is critical for determining the disease identity, transmission method, and exposure list.

• Bioinformatics: This field involves the collection, classification, storage, and analysis of biochemical and biological information using computers. It is used to identify disease pathogens through DNA sequencing.

• The BLAST Program: A tool used to scan DNA sequences. To identify a pathogen:

  1. A sample of Cerebrospinal Fluid (CSF) is taken via a spinal tap (as in the case of bacterial meningitis suspected in Sue Smith).

  2. The CSF is "plated" to grow bacteria.

  3. Bacteria are lysed (blown up) and DNA is isolated.

  4. DNA is amplified and sequenced.

  5. The string of $A$, $T$, $C$, and $G$ is entered into BLAST, which compares it to millions of stored genes to identify the organism.

Enzyme-Linked Immunosorbent Assay (ELISA)

• Principles of Immunology:

  • Antigen: A protein marker on the outside of every living cell or virus used for identification.

  • Antibody: Produced by B lymphocytes (a type of leukocyte); their job is to attach to and neutralize foreign antigens, signaling T lymphocytes to destroy the invader.

• ELISA Procedure:

  1. A tray with small wells is pre-coated with specific antibodies for the pathogen.

  2. Patient serum (or CSF) is added. If the pathogen (antigen) is present, it binds to the antibodies.

  3. Primary Antibody is added to latch onto the trapped antigen.

  4. Secondary Antibody (linked to an enzyme) is added, which attaches to the primary antibody.

  5. A substrate is added. The enzyme acts on the substrate to produce a visible color change.

• Test Results:

  • Qualitative: Observing if a color change occurs (Positive vs. Negative).

  • Quantitative: Measuring the intensity of the color to determine pathogen concentration. This requires a Serial Dilution for comparison.

• Serial Dilution Example: Starting with $100\,ng/mL$, transferring equal parts to subsequent wells results in concentrations of $50$, $25$, $12.5$, and $6.25\,ng/mL$. Comparison helps determine the aggressiveness of the infection and treatment duration.

Antibiotics and Bacterial Resistance

• Bacterial Classification:

  • Gram Negative: Thinner peptidoglycan layer, pinkish-red stain, contains an outer membrane with endotoxins (lipopolysaccharides) and porins. Contains a periplasm fluid layer.

  • Gram Positive: Thick peptidoglycan layer ($20$ times more than Gram Negative), purple stain, no outer membrane or porins, contains teichoic acids.

• Bacterial Structures:

  • Nucleoid: Gel-like region containing the single circular DNA molecule.

  • Plasmids: Small circular DNA carrying non-essential but advantageous genes (e.g., antibiotic resistance).

  • Ribosomes: Sites of protein synthesis.

  • Capsule: Glycocalyx layer for adherence and immune protection.

  • Flagella: Propellers for movement.

  • Pili: Fimbriae for attachment; Sex pilus for conjugation.

• Antibiotic Mechanisms of Action:

  • $\beta$-Lactam Antibiotics: Irreversibly inhibit enzymes involved in cell wall synthesis (peptide bridges in peptidoglycan).

  • Tetracyclines: Reversibly bind to the $30S$ ribosomal subunit, blocking tRNA attachment and stopping protein synthesis.

  • Fluoroquinolones: Inhibit topoisomerases to prevent DNA supercoiling and essential cell processes.

  • Sulfonamides: Competitively inhibit enzymes that bind with $PABA$ in the folic acid biosynthesis pathway.

• Antibiotic Resistance Mechanisms:

  • Conjugation: Bacteria link pili to exchange plasmids.

  • Transformation: Scavenging DNA from dead bacterial cells.

  • Transduction: Resistance delivered via a viral vector.

Hearing Loss: Physics and Anatomy

• Properties of Sound:

  • Intensity: Measured in decibels ($dB$); relates to amplitude (wave height) and loudness.

  • Frequency: Relates to pitch; the number of waves crossing a point per set time.

• Ear Anatomy & Function:

  • Outer Ear: Pinna (collects sound) and Auditory Canal.

  • Middle Ear: Tympanic Membrane (vibrates), Ossicles (Malleus, Incus, Stapes), and Eustachian Tube (pressure maintenance).

  • Inner Ear: Oval Window, Cochlea (fluid waves stimulate hair cells), Cochlear Nerve, and Vestibule (semicircular canals for balance).

• Types of Hearing Loss:

  • Conductive: Damage to outer/middle ear (pinna, canal, eardrum, ossicles). Often medically/surgically correctable.

  • Sensorineural: Damage to the cochlea or auditory nerve. Often permanent; caused by noise exposure or aging.

  • Mixed: Combination of both types.

• Diagnostic Tests:

  • Rinne Test: Compares bone conduction (tuning fork on mastoid process) vs. air conduction. Normal air conduction is twice as long as bone.

  • Speech in Noise Test: Evaluates ability to detect speech against static.

  • Pure Tone Test (Audiogram): Determines the threshold of hearing at frequencies between $250$ and $8000\,Hz$.

• Audiogram Translation:

  • Right Ear = Red Circle; Left Ear = Blue X.

  • Normal: $0-20\,dB$

  • Mild: $21-40\,dB$

  • Moderate: $41-55\,dB$

  • Moderate to Severe: $56-70\,dB$

  • Severe: $71-90\,dB$

  • Profound: $>90\,dB$

Vaccination and Epidemiology

• Vaccination Definition: Injection of dead, weakened, or modified pathogens to activate the immune system and create memory cells.

• Vaccine Production Methods:

  1. Similar-Pathogen: Using a related live virus (e.g., Cowpox for Smallpox).

  2. Attenuated: Weakened live virus adapted to cold environments (e.g., Measles).

  3. Killed: Pathogen killed by heat or radiation (e.g., Polio); often requires boosters.

  4. Toxoid: Uses neutralized toxins (e.g., Tetanus).

  5. Subunit: Uses a small "chunk" of the pathogen (e.g., Hepatitis B).

  6. Naked-DNA: Gene for a protein is placed in a vector (e.g., experimental HIV vaccine).

• Recombinant DNA Technology in Vaccines:

  • Restriction enzymes "cut out" genes; DNA ligase "glues" them into plasmids.

  • Plasmids are inserted into bacteria via heat shock.

  • Bacteria replicate the DNA, which is then extracted for injection.

Genetic Testing and Screening

• Types of Genetic Disorders:

  • Single-Gene: Mutation in one gene (e.g., Sickle cell, Cystic fibrosis). Includes autosomal dominant/recessive and sex-linked (X-linked more common in males).

  • Multifactorial: Combination of multiple genes and environment (e.g., Breast cancer, Diabetes, Alzheimer’s).

  • Mitochondrial: Rare; passed only from mother to child (e.g., Leber’s hereditary optic neuropathy).

  • Chromosomal: Missing or extra chromosomes (e.g., Trisomy 21 / Down’s Syndrome).

• Screening Procedures:

  • Carrier Screening: High-risk adults testing for genes to pass on.

  • Preimplantation Genetic Diagnosis (PGD): Testing one cell of an $8$-cell embryo created via IVf before implantation.

  • Amniocentesis: Fetal cells taken from amniotic fluid after $14$ weeks.

  • Chorionic Villus Sampling (CVS): Placental cells removed earlier than amniocentesis via vaginal needle.

  • Newborn Screening: Blood sample taken shortly after birth (e.g., screening for Tay Sachs in Ashkenazi Jews).

Laboratory Techniques: PCR and Genotyping

• Polymerase Chain Reaction (PCR) Steps:

  1. Denaturation ($95^{\circ}C$): Breaks hydrogen bonds to separate double-stranded DNA.

  2. Annealing ($55^{\circ}C$): Primers bind to the target DNA sequence.

  3. Extension ($72^{\circ}C$): Taq polymerase adds nucleotides to create two double-stranded pieces. Within $1.5$ hours, $1$ copy becomes over $2$ billion.

• Isolation and Centrifugation: Cells are lysed; centrifugation spins heavy components into a pellet at the bottom; Chelex is used to separate DNA into the supernatant.

• Restriction Analysis: Uses restriction enzymes to cut DNA at specific sequences, identifying Single Nucleotide Polymorphisms (SNPs).

• Gel Electrophoresis: DNA fragments move toward the positive end of a buffer chamber; distance traveled correlates to fragment size. Used to determine alleles/genotype.

Cancer: Detection and Treatment

• Characteristics of Cancer Cells: Loss of contact inhibition (cells stack on top of each other), irregular shapes, multiple nuclei, abnormal chromosome numbers, and mutation of cell regulation genes.

• Imaging Technologies:

  • X-ray: Noninvasive; photons pass through soft tissue and are absorbed by bone. $2$-D images.

  • CT Scan: Rotational X-ray producing cross-sectional "slices"; visualizes organs and soft tissue.

  • MRI: Uses magnets and radio waves to detect hydrogen atoms; superior detail for fine soft tissue.

  • Bone Scan: Uses radionuclides (tracers); "hot spots" indicate high metabolic activity or cancer.

• DNA Microarray: Compares gene expression between healthy and cancer tissue.

  • Red: Highly expressed in cancer.

  • Green: Highly expressed in healthy tissue (underexpressed in cancer).

  • Yellow: Expressed equally in both.

• Cancer Genetics:

  • Proto-oncogenes: Normal genes that stimulate division; become Oncogenes when mutated.

  • Tumor Suppressor Genes: Stop growth or induce apoptosis in abnormal cells (e.g., $p53$, $BRCA1$, $BRCA2$).

• Treatment Options:

  • Radiation: Local treatment using selective high-energy rays.

  • Chemotherapy: Systemic treatment via bloodstream; targets all rapidly dividing cells.

  • Biofeedback: Conscious control of involuntary processes to manage pain and stress.

• Pharmacogenetics: Study of how SNPs (e.g., in the $TPMT$ enzyme) affect individual drug responses (e.g., Thiopurines/Azathioprine for Leukemia).

Manufacturing Human Proteins and Organ Failure

• Insulin Production: Produced via bacterial transformation of E. coli. Plasmids are modified with the human insulin gene, inserted via heat shock and calcium chloride, and plated on agar with antibiotics.

• Protein Purification: Bacteria are lysed with lysozyme; fluids are harvested and run through chromatography. Hydrophobic proteins (like GFP) are isolated using high-salt and low-salt buffers.

• Confirmation: SDS-PAGE (vertical electrophoresis) checks protein purity before sale.

• End-Stage Renal Disease (ESRD): Diagnosed via Glomerular Filtration Rate (GFR) and Urinalysis.

  • Dialysis: Hemodialysis (blood filtered by external machine) vs. Peritoneal Dialysis (filtering via the peritoneal membrane in the abdomen).

• Organ Allocation: Regulated by NOTA and OPTN. Based on compatibility, geography, time on list, and age (children preferred). Social status and wealth are excluded.

• Matching Tests:

  • Blood Typing: Finding compatible $A$, $B$, $AB$, or $O$ types and $Rh$ factor.

  • HLA Typing: Matching HLA antigens controlled by the MHC on chromosome $6$.

  • Panel Reactive Antibody (PRA) Screening: Mixing recipient serum with $60$ random donor samples; ideally needs $<50\%$ reaction.

  • Crossmatch: Mixes donor WBCs with recipient serum; agglutination means a positive result and surgery cancellation.

• Future Trends:

  • Xenotransplantation: Species-to-species transplant (e.g., pig heart valves).

  • Tissue Engineering: Growing bladders or skin in the lab.

  • Bionics: Fusion of human and machine (e.g., myoelectric prosthetic arms).

Questions & Discussion

• What is bioinformatics? The use of computer technology to manage and analyze biological data, particularly for pathogen identification using BLAST.

• How does a vaccine activate the body’s immune system? By introducing a harmless version of an antigen, causing the body to produce antibodies and memory lymphocytes.

• What is the goal of PCR? To produce millions of copies of a specific DNA segment for testing.

• How do physical and occupational therapists differ? Physical therapists focus on strength and motor skills (building function); occupational therapists focus on Relearning Activities of Daily Living (ADLs) like eating and grooming.

• What are bioethical concerns for cochlear implants? High cost, potential for complete hearing loss, and being viewed as offensive by the deaf community as an infringement on their culture.