Chapter 1 General Concepts of Disease: Diagnostic Resources.

Chapter 1

General Concepts of Disease:

Diagnostic Resources

Approach to Patient Care – Symptomatic Disease

• The Physical Examination

- Physician looks for and listens for manifestations of disease

Includes: Visual inspection of skin, nails, and oral mucous membranes

Specialized Instruments for Inspection of Structures in Recesses of Body

• Otoscope – allows practitioner to look into the curved ear canal

• Ophthalmoscope – Inspection of retina and back of the eye

• Vaginal Speculum – visual inspection of upper vagina and outer cervix

Physical Exams also include:

• Auscultation – listening for heart and breath sounds with stethoscope

• Percussion – gentle tapping over body cavities to detect changes in the resonance of the chamber (i.e. when there is an accumulation of abnormal fluid)

• Palpation – applying gentle pressure to feel for abnormal growths

• History and Physical Exam are supplemented by special procedures:– Radiologic tests– Lab tests

These are useful in treatment of acute disease – sinusitis, UTI’s, fractures of bones, myocardial infractions, middle ear infections

Can only manage chronic diseases (diabetes, cancer, atherosclerosis etc)

Asymptomatic Disease

• Screening – the attempt to discover disease before it manifests in a patient

• Goal of screening is to either cure a disease by catching it early (i.e. cancer) or to begin treatment early to delay the progression of the disease (i.e. hypertension)

When do We Screen?

• - Likelihood of the patient developing a particular disease

• - Availability of the treatment of the disease

• - Cost of the screening test

Lung Cancer• - Most deadly cancer in the US (causes the

largest number of cancer deaths each year)• Radiographic techniques

– Pros: can detect lung cancer when it is small and potentially curable

– Cons: Are expensive and do confer potential harm to the patient by exposure to ionizing radiation

Best Practice: not ideal for screening entire population but only those with greatest risk (smoking history)

Hypertension

• Onset at all ages and can lead to more serious and chronic diseases

• Screening: Blood Pressure Cuff and Stethoscope

• Treatment: lifestyle modifications and relatively inexpensive pharmaceutical drugs

• Best Practice: Screen all patients at each visit to a practitioner’s office

Cervical Cancer

• Pap Smear – cells are scraped from the surface of the cervix, smeared on a slide, and examined under the microscope for abnormalities

• Dramatically reduced mortality from cervical cancer

• -These screening techniques are reactive – not proactive (most effective way of reducing disease

Purpose and Requirements for Effective Screening

• Benefits of Screening– Should provide some benefit to the person being

screened

• Screening for Genetic Disease– Early identification and treatment of the disease will

favorably influence course of disease.

Diagnostic Tests and Procedures

• Clinical laboratory tests– Purpose: To determine concentration of substances in

blood or urine frequently altered by disease– Uses:

• Determine concentration or activity of enzymes in the blood

• Evaluate function of organs• Monitor response of certain cancers to treatment• Detect disease-producing organisms in urine,

blood, feces• Determine response to antibiotics

Diagnostic Tests and Procedures• Tests of electrical activity: to measure electrical

impulses associated with bodily functions and activities– ECG/EKG: (Electrocardiography) measures serial

changes in electrical activity of the heart in various phases of the cardiac cycle

• Identify disturbances in heart rate, rhythm, abnormal impulses

• Recognize heart muscle injury from ECG abnormalitieshttps://www.youtube.com/watch?v=RYZ4daFwMa8

– EEG: (electroencephalogram) measures electrical activity of brain; brain waves

– EMG: (Electromyography) measures electrical activity of skeletal muscle during contraction and at rest

Diagnostic Tests and Procedures

• Radioisotope (radionuclide) studies: evaluate organ function by determining rate of uptake and excretion of substances labeled with a radioisotope

• Uses:– Anemia: radioisotope-labeled vitamin B12– Hyperthyroidism: radioactive iodine– Pulmonary blood flow: albumin; to detect presence of

blood clots– Cancer spread: phosphorus; to determine presence of

tumor deposits in bone or spine– Heart muscle damage: evaluate blood flow

Diagnostic Tests and Procedures• Endoscopy

– To examine interior of body using rigid or flexible tubular instruments equipped with lens and light source

– To perform surgery formerly done through large abdominal incisions

• Bronchoscope: trachea and major bronchi• Cystoscope: bladder• Laparoscope: abdomen

Bronchogram showing normal caliber and branching of bronchi and bronchioles

© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

• Ultrasound– Mapping echoes produced by high-frequency sound

waves transmitted into body; echoes reflect change in tissue density, producing images

– Greatest contrast is provided where soft tissues and liquids meet

– Most useful in studying cystic structures(gallbladder, urinary bladder, and the gravid (pregnant) uterus).

– Procedure of choice for detecting gallstones

• In pregnancy it can be used without risk of radiation to the fetus (twins, ectopic pregnancies, structural abnormalities of fetus and placenta, heart defects can be detected)

Radiologic Procedures

• Radiology – discipline of medicine that uses techniques such as X-rays, CT scans, and nuclear medicine to diagnose disease

• X-ray– Principle: use of high-energy radiation waves at lower

doses to produce images to help diagnose disease– Can penetrate through tissues at varying degrees

depending on tissue density – Act on a photographic film or plate (roentgenogram)

as the rays leave the body

• Radiopaque: appears white on film; high-density tissues such as bone absorb most of the rays

• Radiolucent: appears dark on film; low-density

tissues allow rays to pass through

• X-ray can include use of contrast media to outline structures not otherwise visualized on standard films– Barium sulfate: intestinal tract – Radiopaque oil: bronchogram– Intravenous dye: intravenous pyelogram; urinary tract– Radiopaque tablets: visualize gallstones– Arteriogram: visualize blood flow, identify narrowing or

obstruction– Cardiac catherization: blood flow through heart, detect

abnormal communications between chambers

X-ray of colon with radiopaque barium sulfate© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

X-ray of gallbladder; gallstones appear as radiolucent (dark) within a radiopaque bile (white)

Opened gallbladder, same patient

© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

Carotid angiogram, narrowing of carotid artery© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

• Computed tomographic (CT) scans (sophisticated X-rays)– Principle: radiation detectors record

amount of X-rays or ionizing radiation

absorbed by body and feed data into a computer that reconstructs the data into an image

– Radiopaque and radiolucent tissues appear white and dark as in a conventional x-ray

– Individual organs sharply demarcated by planes of fat that appear dark because of its low density

– Delivers higher dose of ionizing radiation than x-ray

• Uses of computed tomographic (CT) scans– Cancer screening asymptomatic individuals– Detect abnormalities in internal organs that

cannot otherwise be identified by standard x-ray (intracerebral hemorrhages, pulmonary embolisms, aortic dissection, kidney and pancreatic cancers, liver abscess, gallstones)

CT scan, abdomen at level of kidneys, fluid-filled cysts, right kidney

© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

• Magnetic resonance imaging (MRI)– Principle: computer-constructed images of body

based on response of hydrogen protons in water molecules when placed in a strong magnetic field

– (does not use X rays)

• Protons align in the direction of the magnetic field• Protons are temporarily dislodged and wobble

when radiofrequency waves are directed at them• Protons emit a measurable signal (resonance) that

can be used to construct images• Intensity of resonance depends on water content

of tissues, strength and duration of radiofrequency pulse

• MRI: advantages over CT scan– Does not use ionizing radiation– Can detect abnormalities in tissues surrounded by bone, such

as spinal cord, orbit, skull– Bone interferes with scanning because of its density but does

not produce an image in MRI because of its low water content – However, individual must remain still for very long periods of

time, confinement and noise often intolerable to patients; expensive

• Uses– Orthopedic (bone and joints), neurologic (brain and nerve)

Multiple sclerosis– Superior to mammography in detecting breast cancer– https://www.youtube.com/watch?v=8oI9YnhPNcQ

MRI, brain, with malformation within brain stem© Courtesy of Leonard Crowley, M.D./University of Minnesota Medical School

• Positron emission tomography (PET)– Principle: Measures metabolism of

biochemical compounds that are labeled with positron-emitting isotopes (C, O, N) to measure organ function, example glucose

– Disadvantages• Very expensive and not widely available• Requires facilities for incorporating the isotopes

into the biochemical compound

• Uses of PET– Assess biochemical functions in brain

– Determine metabolic activities of organ or tissue; specific site in an organ where compound is metabolized

– Evaluate changes in blood flow in heart muscle following a heart attack

– Distinguish benign from a malignant tumor (increased glucose uptake in malignant versus benign tumors)

Anatomic Pathology Tests and Procedures

• Surgical Pathology – diagnosis of lesions in pieces of tissue removed from a patient– Based on gross (naked-eye) and microscopic

examination by pathologistGross appearance (melanoma)

Records size, color, and texture of the lesion and

Relationship to surrounding structures

(microscopic biopsy)

(on skin) (cut)

BiopsyBiopsy: tissue samples obtained for histologic (tissue) examination to determine abnormal structural and cellular patterns accompanying disease

• Liver, kidney, bone marrow–Partial (incisional) biopsy: only part of the lesion is removed. Used for primary diagnosis–Needle biopsy – inserts needle into solid organ and aspirates a core of the tissue (liver, kidney, and prostate disease)

Excisional Biopsy• Remove in entirety a small lesion

– Done for both diagnosis and treatment– Removal of large specimens in operating

room is called a resection (primarily used for treatment purposes)

– Usually require 1-2 days for preparation under the microscope slide

– Rapid diagnosis a frozen section can be prepared in minutes

Cytology

• Background Information:– Specimens consist of cells sloughed or

scraped from body surfaces– Examined primarily to detect cancer cells– Cytotechnologist will examine stained smears– Pathologist interprets any abnormalities– Any body fluid (urine, sputum, cerebrospinal

fluid, pleural fluid) can be used– Majority are from PAP smears

Fine Needle Aspiration (FNA)

• Uses a small caliber needle to obtain specimens for cytologic examination

• Is faster and less expensive than open biopsy

• However, specimen is not always adequate to provide diagnosis

• Video: FNA liver

https://www.youtube.com/watch?v=MaShkXjse-U

Clinical Pathology Tests• Areas of laboratory medicine:

– Part of pathology that performs lab tests on tissues and fluids

– Subdivided into:• Chemistry- blood glucose, cholesterol and other lipids, kidney and liver

tests

• Hematology• Microbiology• Immunopathology (detection of antigens and antibodies in blood and

tissue and the study of lymphocytes – WBC’s)

• Blood bank (transfusion medicine) – procurement, typing, testing, processing, storage, and administering blood components as well as monitoring adverse reactions to transfusions

Hematology- Blood

• A complete blood count (CBC) most common hematologic test– Consists of:

• measurement of hemoglobin• Counting RBC and WBC• Microscopic evaluation of morphologic (form)

changes in blood cells

Special tests for anemia and blood coagulation

CBC Report

Bacterial Culture

• Most common test performed in microbiology lab

• Bacteria easily grown and tested for sensitivity to antibiotics

Bacterial Sensitivity Chart

Cytogenetics

• Examining chromosomal and genetic makeup of cells to diagnose and detect disorders such as trisomies, translocations, and deletions known to cause disease

Molecular Diagnosis

• Have become extremely important diagnostic tools to detect human disease

• Goes beyond what can be seen with the naked eye (or microscope) to determine the “molecular signature” of a growth (neoplasm/tumor) or microorganism

• Each microorganism and tumor has a unique signature of genes that pathologists can use to identify it

• Tumors that appear identical under the microscope, yet have vastly different prognoses (and requires different treatments), can be separated and identified on their DNA profiles

• Involves genetic sequencing

Polymerase Chain Reaction (PCR)

• Sequences short stretches of a gene

• Involves amplifying (increasing) numbers of a gene or nucleic acid

• Example: If a particular viral infection is suspected, PCR of the viral nucleic acid can be performed on a patient’s blood sample. Fluorescent probes can then detect the viral nucleic acid (DNA or

RNA)

Proteomics• Maps the pattern of proteins involved in

supporting cancerous growths

• Uniqueness in the proteins will identify the type of tumor as well as its growth.

• Uses mass spectroscopy

• We now have the ability to amplify and sequence large numbers of genes and proteins.

• The new insights that we have are leading to more targeted patient care for the treatment of diseases

Pharmacogenomics• Predicts a particular patient’s response to

drugs on the basis of a person’s genetic makeup

• Genes that code for enzymes used in drug metabolism are determined so that the proper dose can be calculated

• http://medprofvideos.mayoclinic.org/videos/pharmacogenomics-right-drug-right-dose-right-time

Targeted Therapy• Treatment with a particular drug if the

substance in which they act upon is known to be present.

• Ex. Breast cancer – patient is routinely tested for estrogen and progesterone receptors and a particular growth factor receptor. If present, they are blocked by pharmaceutical agents so that tumor cells do not respond and growth of tumor is limited

• Pathologists apply molecular methods to diagnose inherited disorders, cardiovascular diseases and immunoglobulin activities

• https://www.youtube.com/watch?v=6UXxmTFsNf0

Discussion

• What are the underlying principles for these diagnostic procedures: x-ray, CT scan, MRI, PET?

• Explain the requirements for an effective screening.

• Differentiate:– Symptomatic versus specific treatment– Sign versus symptom– Symptomatic versus asymptomatic disease– Diagnosis versus prognosis