Intro to Medical History, Disease, and Diagnostic Tests

Course exam format (Forsthuber)

4 multiple-choice exams; best 3 of 4 count. Exams are based on the handouts. L1_Intro_History

Greek medicine: the four humors

Blood, phlegm, yellow bile, black bile. Moved from supernatural to natural causes, but theories were not tested (little/no human dissection or autopsy). L1_Intro_History

Who was Imhotep and when?

~2650 BC; pyramid builder and physician to the pharaoh. Speculated to be the original author of the Edwin Smith Papyrus. L1_Intro_History

Edwin Smith Papyrus

Earliest known writing on medicine. Covers trauma surgery, anatomy, diagnosis/treatment of 48 conditions (incl. heart failure). Bought 1862 by Edwin Smith. L1_Intro_History

Hippocrates (460-377 BC)

Founded a school of physicians; credited with the Hippocratic Oath; taught careful observation and reporting of symptoms; helped develop four-humor theory. No human dissection. L1_Intro_History

Celsus (30 BCE - 38 CE)

Roman medical writer; described the cardinal signs of inflammation in 'De Medicina'. L1_Intro_History

Galen (129-216 CE)

Greek physician in the Roman Empire; physician to gladiators in Pergamon; dominated medical teaching >1,000 years. Showed arteries contain blood (not air/pneuma), kidneys make urine, nerves/spinal cord control movement. Some errors because of animal (not human) dissection. L1_Intro_History

Leonardo da Vinci (1452-1519)

Learned from human dissection about muscles, bones and tendons. L1_Intro_History

William Harvey (1578-1657)

Showed the heart moves blood through the body. Book: 'De Motu Cordis et Sanguinis'. L1_Intro_History

Rudolf Virchow (1821-1905)

Father of modern pathology; founded cellular pathology (disease arises from altered cells/tissues seen by microscope). First recognized leukemia; coined 'embolism'; Virchow's node. L1_Intro_History

Virchow's node

Enlarged LEFT supraclavicular lymph node; early sign of gastric cancer. L1_Intro_History

Edward Jenner (1749-1823)

First systematic vaccination; cowpox protects against smallpox. L1_Intro_History

Ignaz Semmelweis (1818-1865)

Showed sanitary conditions save lives; compared childbed fever in midwife vs doctor/student wards. 'Savior of mothers'. L1_Intro_History

Robert Koch (1843-1910)

Founder of modern bacteriology; discovered causes of tuberculosis, cholera, anthrax. L1_Intro_History

Louis Pasteur (1822-1895)

Principles of vaccination, fermentation, pasteurization; first vaccines for rabies and anthrax. L1_Intro_History

Sigmund Freud (1856-1939)

Father of psychoanalysis. L1_Intro_History

Joseph Lister (1827-1912)

Father of antiseptic surgery; used phenol (carbolic acid) on instruments, wounds, dressings. L1_Intro_History

George Papanicolaou (1883-1962)

Showed a vaginal smear can detect uterine cancer (1943); pioneer of early cancer detection (Pap smear). L1_Intro_History

Alexander Fleming (1881-1955)

Discovered penicillin (1928: Penicillium notatum mold inhibited Staph aureus) and researched lysozyme. L1_Intro_History

Define 'disease' (broadest sense)

Undesired deviation from the norm (the 'generally accepted standard'). L1_Intro_History

Sign vs symptom

SIGN = seen/measured by clinician or tests (fever, high BP, bleeding). SYMPTOM = reported by patient, can't be measured (pain, drowsiness, vertigo). L1_Intro_History

The four pillars of understanding disease

Etiology -> Pathogenesis -> Lesion (morphologic change) -> Functional changes (clinical manifestation). L1_Intro_History

Etiology (with example)

The cause of disease: infection, injury, genetic defect. Ex: Streptococcus pneumoniae infection of the lungs. L1_Intro_History

Pathogenesis (with example)

The disease process/mechanism. Ex: strep infection -> lung damage, inflammation, fluid accumulation. L1_Intro_History

Lesion (with example)

Morphologic/ultrastructural change in tissue. Ex: bacterial pneumonia -> lobar consolidation, inflammatory infiltrates, lung edema. L1_Intro_History

Functional changes (with example)

Impaired organ-system function = clinical manifestation. Ex: lobar bronchopneumonia -> fever, pain, malaise, possibly death. L1_Intro_History

Ways to recognize pathologic alteration

Patient report; gross exam (naked eye); histologic exam (microscope); lab exam (blood, urine, DNA); specialized exams (X-ray, US, endoscopy, MRI). L1_Intro_History

Four cardinal signs of acute inflammation (Celsus)

Rubor (redness), Tumor (swelling), Dolor (pain), Calor (heat). L1_Intro_History

Fifth cardinal sign (Galen/Virchow)

Functio laesa = impaired function. L1_Intro_History

Inflammation timeline: 0-4 h

Preformed factors (antibodies, complement, serum & vasoactive factors). Signs: rubor, calor. L1_Intro_History

Inflammation timeline: 4-48 h

Influx of neutrophils. Signs: rubor, calor, dolor, tumor. L1_Intro_History

Inflammation timeline: 24-96 h

Influx of macrophages (start repair, clear dead tissue). Signs: all five incl. functio laesa. L1_Intro_History

Inflammation timeline: >96 h

Adaptive immunity: T lymphocytes activated and migrate to site. Signs: dolor, tumor, functio laesa. L1_Intro_History

How a clinical diagnosis is reached

Current illness (emergency/life-threatening?) -> patient history -> physical exam -> diagnostic tests. L1_Diagnostic_Tests_Pt1

Key questions for 'current illness'

When did it start? First time? Better, worse, or stable? What did the patient try and did it help? If prior episodes, any significant change? L1_Diagnostic_Tests_Pt1

Physical exam principles

Cultivate observation; be systematic; develop a routine; know your tools (stethoscope). L1_Diagnostic_Tests_Pt1

Non-invasive vs invasive procedure

Non-invasive: doesn't break the skin (inspection, reflexes, urine test, throat swab, X-ray, US, MRI, CT, ECG). Invasive: breaks skin (blood draw, spinal tap, biopsy, endoscopy). No universally accepted definition. L1_Diagnostic_Tests_Pt1

CBC

Complete blood count (+ differential). L1_Diagnostic_Tests_Pt1

CMP

Comprehensive metabolic panel: electrolytes (Na, K, Cl, Ca), glucose, BUN, creatinine, liver enzymes (AST, ALT), etc. L1_Diagnostic_Tests_Pt1

ESR: modern usefulness

Erythrocyte sedimentation rate; today mainly useful for myeloma, temporal arteritis, polymyalgia rheumatica. L1_Diagnostic_Tests_Pt1

Other lab tests: urine, stool, CSF

Urine: protein, microorganisms, pH, blood. Stool: blood, parasites, fat. CSF: cells, proteins, microorganisms. L1_Diagnostic_Tests_Pt1

Normal RBC count and Hb

RBC ~5 x10^6/uL. Hb ~14-16 g/dL (dL = 100 mL). L1_Diagnostic_Tests_Pt1

Normal WBC count (CBC slide range)

~4-10 (x10^3/uL) on the slide; fishbone chart lists 4.5-11. Infection -> increased WBC. L1_Diagnostic_Tests_Pt1

Erythrocyte terms: increase / decrease

Increase: erythrocytosis or polycythemia. Decrease: anemia (or erythroblastopenia). L1_Diagnostic_Tests_Pt1

Leukocyte terms

Increase: leukocytosis. Decrease: leukopenia. L1_Diagnostic_Tests_Pt1

Lymphocyte terms

Increase: lymphocytosis. Decrease: lymphocytopenia. L1_Diagnostic_Tests_Pt1

Granulocyte / neutrophil / eosinophil terms

Granulocytosis vs granulocytopenia/agranulocytosis; neutrophilia vs neutropenia; eosinophilia vs eosinopenia. L1_Diagnostic_Tests_Pt1

Platelet terms

Increase: thrombocytosis. Decrease: thrombocytopenia. L1_Diagnostic_Tests_Pt1

Pancytopenia

Decrease in ALL cell lines. L1_Diagnostic_Tests_Pt1

CBC fishbone layout

Hgb at top of the 'Y'; WBC on left; Plt (platelets) on right. Ex: Hgb 16, WBC 8.9, Plt 275. L1_Diagnostic_Tests_Pt1

Chemistry fishbone normals (adult)

Na 135-145; Cl 97-107; BUN 8-21; Glu 70-100; K 3.5-5.0; CO2 22-26; Creat 0.6-1.2. L1_Diagnostic_Tests_Pt1

Hematology fishbone normals (adult)

WBC 4.5-11; Hgb 12.0-17.5; Hct 34-52; Plt 150-450. L1_Diagnostic_Tests_Pt1

Coag fishbone normals (adult)

PT 10-13; PTT 25-35; INR 0.8-1.2. L1_Diagnostic_Tests_Pt1

Blood smear: lymphocyte vs neutrophil

Lymphocyte: round dark nucleus, little cytoplasm. Neutrophil: multi-lobed nucleus. Eosinophil: bilobed nucleus with red granules. Basophil: dark purple granules. L1_Diagnostic_Tests_Pt1

Sickle-shaped cells on a smear

Abnormal RBCs (sickled/elongated cells). L1_Diagnostic_Tests_Pt1

Large blasts with big nuclei on a smear

Abnormal WBCs: myeloid cells -> suggests myeloid leukemia. L1_Diagnostic_Tests_Pt1

Electrocardiogram (ECG/EKG)

Measures electrical activity of the heart. EEG = brain. EMG = muscle. L1_Diagnostic_Tests_Pt1

Normal cardiac conduction path

SA (sinoatrial) node -> AV (atrioventricular) node -> ventricles. L1_Diagnostic_Tests_Pt1

P wave

Atrial depolarization. L1_Diagnostic_Tests_Pt1

QRS complex

Ventricular depolarization. L1_Diagnostic_Tests_Pt1

T wave

Ventricular repolarization. L1_Diagnostic_Tests_Pt1

ST elevation on ECG

Sign of myocardial infarction (MI). L1_Diagnostic_Tests_Pt1

Ventricular flutter

'Bad': ~250-300 beats/min, sinusoidal waves. L1_Diagnostic_Tests_Pt1

Ventricular fibrillation (V-fib)

'Worse': no clear electrical activity. L1_Diagnostic_Tests_Pt1

X-rays: discovery

Wilhelm Roentgen, 1895, while working with a cathode-ray tube (fluorescent screen glowed). Passes through soft tissue, not bone or metal. L2_Diagnostic_Tests_Pt2

Wavelengths: visible light, X-ray, gamma

Visible ~6000 angstroms (400-700 nm); X-ray ~1 angstrom (0.1 nm); gamma ~0.0001 angstrom (

Radiation dose units

Sievert (Sv). 1 Sv = 100 rem. L2_Diagnostic_Tests_Pt2

Radiation benchmarks (mSv)

Chest X-ray 0.10; natural background 2/yr (= 20 chest X-rays); full-body CT 10; heart CT 16; 100 = 1,000 chest X-rays (lowest annual dose with clear cancer increase); ~1,000 = radiation sickness; ~5,000 = kills half within a month. L2_Diagnostic_Tests_Pt2

Chernobyl reactor dose rate

200 Sv/hr (20,000 rem). Control-room staff died within ~2 weeks. L2_Diagnostic_Tests_Pt2

Chernobyl control-room tourism

1.13 mSv per 5 minutes ~ 10 chest X-rays per 5 min. L2_Diagnostic_Tests_Pt2

What shows up well on plain X-ray?

Bones and dense tissue. Soft tissues (lung) are harder to see. L2_Diagnostic_Tests_Pt2

Computed radiography (CR) vs digital radiography (DR)

CR = photostimulable phosphor plates (reusable cassettes). DR = flat-panel digital detector, no film cassettes, read directly by computer; replacing CR in many hospitals. L2_Diagnostic_Tests_Pt2

Uses of plain X-ray (examples)

Fractures (wrist, femur/hip: hip fractures raise mortality in elderly), lung cancer, pneumonia (lobar), bone lesions (plasmacytoma/mets). L2_Diagnostic_Tests_Pt2

CT scan: how it works

Motorized scanner circles the patient; many serial X-ray images compiled into a 3-D image. More detail than X-ray. L2_Diagnostic_Tests_Pt2

CT vs X-ray radiation

Each CT slice uses lower-intensity X-rays, but overall exposure is significantly higher than plain X-ray. L2_Diagnostic_Tests_Pt2

Enhanced X-ray studies with contrast

Contrast material outlines vessels, e.g., brain aneurysm (weak-walled blood pouch that can rupture; may be congenital). L2_Diagnostic_Tests_Pt2

Nuclear medicine

Patient injected with radioactive material (e.g., I-131) that concentrates where activity is highest. Ex: thyroid adenoma, metastatic thyroid cancer. L2_Diagnostic_Tests_Pt2

MRI: how it works

Strong magnet + radio-frequency waves. Atoms align; when the RF pulse stops they relax and emit signals that are recorded. Best for soft tissues (brain, muscle, organs). L2_Diagnostic_Tests_Pt2

MRI safety

Strong magnet: no ferromagnetic objects (iron, steel) in room. Very loud: earplugs/headphones. L2_Diagnostic_Tests_Pt2

T1 vs T2 MRI

T1: only FAT bright (water dark); best for normal anatomy. T2: WATER and FAT bright ('Water is White in T2' = WW2); best for pathology. L2_Diagnostic_Tests_Pt2

Gadolinium

MRI contrast agent; gives bright signal; helps visualize blood vessels/structures. L2_Diagnostic_Tests_Pt2

MRI example: multiple sclerosis

Plaques/lesions seen in brain on T2 scan. L2_Diagnostic_Tests_Pt2

PET scan

Positron emission tomography: inject radioactive tracer; detects gamma rays; shows METABOLIC activity. L2_Diagnostic_Tests_Pt2

Ultrasound

Transducer emits high-frequency sound (>20,000 Hz); echoes reflect differently by tissue density. Painless, works through skin (heart, vessels, organs). L2_Diagnostic_Tests_Pt2

Biopsy

Tissue obtained for histologic exam (e.g., breast biopsy, bone marrow biopsy). L2_Diagnostic_Tests_Pt2

Histology vs cytology

Histology: intact tissue, morphology preserved. Cytology: cells recovered (usually single cells), architecture not preserved (Pap smear, BAL, urine cytology). L2_Diagnostic_Tests_Pt2

Tissue processing

Tissue removed by needle/surgery, fixed or frozen; pathologist inspects, describes, marks and dissects it. Usually embedded in paraffin. L2_Diagnostic_Tests_Pt2

Frozen section

Quick freezing (butanol/liquid nitrogen); done during surgery to give the surgeon fast information. L2_Diagnostic_Tests_Pt2

H&E stain

Hematoxylin = basic dye, stains nucleic acids (nucleus) BLUE. Eosin = acidic dye, stains cytoplasm RED/PINK. L2_Diagnostic_Tests_Pt2

PAS stain

Periodic acid-Schiff: glycogen (liver/muscle); fungi stain PAS positive. L2_Diagnostic_Tests_Pt2

Masson's trichrome

Stains collagen (e.g., liver cirrhosis/fibrosis). L2_Diagnostic_Tests_Pt2

Immunofluorescence (IF)

Identifies specific cell types/tissues/molecules. Ex: immunoglobulins and complement in post-infectious glomerulonephritis. L2_Diagnostic_Tests_Pt2

Three cellular responses to stress/injury

1) Adapt (survive) 2) Cell injury (damaged, may recover) 3) Cell death (severe). L3_Mechanisms_Tissue_Injury

Macroscopic vs microscopic changes

Macroscopic (organ level, naked eye): hypertrophy, atrophy, dysplasia, pigmentation, calcification, fatty change. Microscopic: pigment/inclusions (iron, fat, lipofuscin), multinucleation, apoptosis, necrosis. L3_Mechanisms_Tissue_Injury

Hypertrophy

Cells increase in size (organ may enlarge). Occurs in dividing AND non-dividing cells. Not always abnormal. L3_Mechanisms_Tissue_Injury

Hyperplasia

Increase in NUMBER of cells; only in dividing cells. L3_Mechanisms_Tissue_Injury

Atrophy

Cells/organ shrink. L3_Mechanisms_Tissue_Injury

Metaplasia

One mature cell type changes to another in a specific location, due to chronic stress/injury. Increases cancer risk. L3_Mechanisms_Tissue_Injury

Stimulus -> adaptation match: Increased demand/chronic stimulation

hypertrophy, hyperplasia.

Physiologic hypertrophy example

Pregnant uterus (also physiologic atrophy: uterus shrinks after pregnancy). L3_Mechanisms_Tissue_Injury