Outline the scope of the introductory course in pathology and clinical pathology. Describe the announced criteria for passing, and the factors that will be considered in any narrative performance summary. Give the title or nickname of the course text or the last name of its first author.

Describe the scope of pathology as a discipline. Distinguish general, systemic, anatomic, and clinical pathology. Mention at least three things a pathologist does when he or she is not teaching medical students! Tell how to contact your pathology instructors.

Identify Rudolf Virchow as the founder of modern pathology. Explain briefly the idea that pathology deals with human beings from the molecular to the social levels, and mention at least one health problem "caused by politicians".

Explain why we call our approach to pathology "scientific", and why we believe that we are telling you the truth. Distinguish various levels of scientific statements ("theory", "hypothesis", etc.) Answer common criticisms of pathology education made by non-physicians. Mention and justify at least one criterion for evaluating a media health claim.

Define iatrogenic disease, mention the extent of the problem, give at least two examples, and explain why some iatrogenic disease is acceptable. Comment on the application of Hippocrates' dictum, "First Do No Harm" to today's medical practice.

Mention how we screen for color-blindness, and tell what a color-blind student should do in lab.

Pathology is the scientific study of disease. Disease could reasonably be defined as internal problems that cause pain and/or interfere with a person's ability to work, play, and/or love others.

Injuries (mechanical, chemical, electrical, or thermal), poisonings, and bad habits may or may not be included in someone's definition of disease.

The social pathology that leads to disease is often listed among a patient's problems. Dr. Virchow, the founder of modern pathology, considered it a principal mechanism of disease, though it falls outside the domains of anatomic and clinical pathology.

There are several thousand distinguishable diseases. Generally, we will not tell you in this course about diseases that affect fewer than 1 in 20,000 people during their lifetimes.

Doctors talk about disease and other human tragedy without showing obvious emotion. We are sometimes asked how we can do this. Knowing the truth about our problems is essential before we can do much about them.

INEVITABLE, SERIOUS DISEASES: Everyone who lives long enough will probably get:

Atherosclerosis: an accumulation of cholesterol and debris in cells of the intimal layer of the large arteries, eventually ruining the artery. Some atherosclerosis is inevitable.

Alzheimer's changes: the anatomic lesions of Alzheimer's appear in the brains of most, probably all, elderly people. Symptomatic Alzheimer's may or may not be inevitable.

Osteoarthritis: irreversible wear-and-tear and age-related changes in joints.

Osteoporosis: irreversible loss of the substance of bones

Senile macular degeneration: Central blindness due to old age

Senile cataract: Opacification of the lens due to old age

OUR VERY COMMON, SERIOUS DISEASES

Atherosclerosis remains our most ubiquitous health problem. It kills a majority of US citizens. The epidemic peaked in 1968, and atherosclerosis will soon be second to cancer as a killer of Americans.

Atherosclerosis begins during the first year of life.

Severe atherosclerosis causes transient ischemic attacks, strokes, angina pectoris, heart attacks, ruptured aortic aneurysms, leg claudication, bowel ischemia, kidney destruction (by "atheroembolization") and gangrene of the legs.

Whether atherosclerotic plaques in humans can be made to go away is a subject of debate today. In the animal models, it is largely reversible. I predict that during the next few years, cardiologists will focus on "vulnerable plaque" (i.e., the lipid-rich areas that actually cause most of the trouble) and discover that it often shrivels to nothing when coronary risk factors are eliminated.

Cancers ("malignant neoplasms") are groups of cells that grow as if they were a new organ, invade and destroy normal tissue, and spread to remote sites by the bloodstream or lymph vessels.

These develop in approximately 35% of US citizens (1,334,100 new cases this year, 556,500 deaths).

The higher incidence in men is mostly explained by more incidental prostate cancers. The higher mortality in men is mostly explained by men having been smoking longer.

The commonest cancers in male humans (#'s: 2003)

(1) Prostate cancers (220,900 new cases this year; 28,900 deaths; lung cancer used to be more common,and plus prostate cancer is being diagnosed much sooner)

(2) Lung cancers (91,800 new cases this year; total rate is declining!; 88,400 deaths, obviously as lethal as ever)

(3) Colon-rectum cancers (72,800 new cases this year, 28,500 deaths)

(4) Bladder cancers (42,200 new cases this year; 8600 deaths)

(5) Lymphomas and myeloma (40,100 new cases this year; 17,500 deaths)

(6) Melanomas (29,900 new cases this year; 4700 deaths)

(7) # Kidney cancers (19,500 new cases this year; 7400 deaths)

(8) Oropharynx cancers (18,200 new cases this year, 4800 deaths, going down)

(9) # Leukemias (17,900 new cases this year; 12,100 deaths)

(10) Pancreas cancers (14,900 new cases this year; 14,700 deaths; very lethal cancer);

(11) Stomach cancers (13,400 new cases this year; 7000 deaths)

(12) Liver and biliary cancers (14,800 new cases this year; 10,500 deaths)

(13) Esophagus cancers (10,600 new cases this year; 9900 deaths; very lethal cancer)

(14) # CNS cancers (10,200 new cases this year; 7300 deaths)

(15) Larynx cancers (7100 new cases this year, thankfully declining; 3000 deaths)

The commonest cancers in female humans:

(1) Breast cancers (211,300 new cases this year; 39,800 deaths; the rate probably is stable, while the death rate is declining significantly)

(2) Lung cancers (80,100 new cases this year, will soon catch up with the men; 68,800 deaths, making it the #1 cancer killer of women by a solid margin)

(3) Colon-rectum cancers (74,700 new cases this year; 28,800 deaths)

(4) Endometrium cancers (40,100 new cases this year; 6800 deaths)

(5) Lymphomas and myelomas (35,500 new cases this year; 17,360 deaths)

(6) Ovary cancers (25,400 new cases this year; 14,300 deaths)

(7) Melanomas (24,300 new cases this year; 2900 deaths)

(8) Bladder cancers (15,200 new cases this year; 3900 deaths)

(9) Pancreas cancers (15,800 new cases this year; 15,300 deaths; very lethal cancer)

(10) Thyroid cancers (16,300 new cases this year; 800 deaths)

(11) # Leukemias (12,700 new cases this year; 9800 deaths)

(12) Uterine cervix cancers (12,200 new cases this year, 4100 deaths; despite low U.S. rates, this is the great cancer killer of young women worldwide)

(13) # Kidney cancers (12,400 new cases this year; 4500 deaths)

(14) Oropharynx cancers (9500 new cases this year; 2400 deaths)

(15) Stomach cancers (9000 new cases this year; 5100 deaths)

(16) # CNS cancers (8100 new cases this year; 5800 deaths)

"#" designates categories that contain a large number of pediatric patients.

NOTE: Small skin cancers that are easily cured are not included. These categories include cancers of all degrees of aggressiveness that arise in a particular organ. For example, the common lung cancers are still nearly 100% fatal, but some cancers that arise in the lungs are slow-growing, and intercurrent disease can kill these patients.

High blood pressure ("hypertension") means increased systemic systolic and/or diastolic pressure.

High blood pressure eventually affects 15% of US citizens. The causes may be apparent but are usually mysterious.

Complications of most forms of high blood pressure include accelerated atherosclerosis, strokes, heart pump failure, brain malfunction, and kidney damage.

Not everyone with occasional elevated blood pressure readings is sick. The significance of such "labile hypertension" remains unclear.

Emphysema (loss of the elasticity in the lung air spaces) and chronic bronchitis (longstanding inflammation of the larger airways) are very troublesome.

These are very common, and are to be expected in cigaret smokers and those who must breathe polluted air.

Diabetes mellitus means lack of insulin or resistance to its actions.

Maybe 5% of US citizens eventually get some form of diabetes. Today, its most serious consequences are damage to the arteries, arterioles, eyes, kidneys, and nerves.

Bacterial pneumonias are infections within the alveoli of the lungs.

These often affect people with underlying physical problems. Bacterial pneumonia is a common mechanism of death in these people.

Aspiration pneumonias result from getting something bad (especially stomach contents) into the airways.

This is a very common mechanism of death in people with underlying physical or substance-abuse problems.

Actually most bacterial pneumonias are the results of aspiration of micro-organisms from the mouth.

Tuberculosis: a special bacterial pneumonia that was once a major killer of healthy young people.

TB infection is still common, but serious disease is controllable.

Deep vein thrombosis: a blood clot in the deep veins, usually of a leg.

This is a minor problem by itself, but if the clot breaks off, it can cause sudden death by traveling to the pulmonary arterial tree. When this happens, it is called a pulmonary thromboembolus ("blood clot in the lung").

Child abuse and neglect

This has always been widespread, but it has only recently been recognized as important. Although it is reported much more often today, I know of no reason to believe that its prevalence in the US is increasing.

Psychoneuroses

Anxiety, depression, agoraphobia, panic attacks, and related phenomena that appear to result (at least in part) from one's experiences rather than from well-defined organic changes. The basic ability to test reality is preserved.

Somewhere between 10% and 70% of US citizens are impaired by psychoneuroses on any given day.

Emotional overlay ("the supratentorial component") is important in most serious illness.

Alcoholism: loss of self-control in drinking ethyl alcohol.

Around 10% of US citizens ultimately become alcoholics. This is harmful to them and to their families, employers, and other associates.

If you feel a compulsion to drink, or cannot stop after one drink, then you must stop for the rest of your life. If you don't care about yourself, then at least do this for the sake of those around you.

Around one US citizen in three presently has a serious personal problem because of an alcoholic.

Nicotine addiction

This is the principal risk factor for:

lung cancer
emphysema/chronic bronchitis
Buerger's thromboangiitis obliterans (only rare one on the list)

Combined with alcoholism, it is the principal risk factor for:

mouth and throat cancer
esophageal cancer
larynx cancer

It is an important risk factor for:

atherosclerosis/sudden cardiac death
bladder cancer
gum disease
kidney cancer
pancreas cancer
upset stomach and peptic ulcer
household fires

Today, most new nicotine addicts are adolescents. Cigaret smoking, once macho, is now a teenaged girl's vice.

NOTE: Human beings are selectively fearful. Consider smokers who won't try a single parachute jump "because you can get killed"....

Osteoporosis

This disables many older people, especially older women. It can produce chronic pain, collapsed vertebral bodies, fractured hips, etc., etc.

Osteoarthritis

This causes pain and interferes with movement.

Alzheimer's disease

This eventually results in profound loss of mental function.

Alzheimer's disease includes "senility". Around 15% of US citizens have it when they die.

HIV virus infection (AIDS virus infection)

Iatrogenic disease

OUR VERY COMMON, USUALLY LESS SERIOUS DISEASES (NON-DISEASES, ETC.):

Each of these affects 5% or more of US citizens at risk sometime during their lives. Some can be fatal, others are only trivial.

Bacterial diseases

boils
cellulitis
strep throats
bacterial conjunctivitis
bacterial ear infections
impetigo
food poisoning (especially staphylococcal)
bacterial diarrheas ("Montezuma's revenge", etc.)
gonorrhea (one million cases yearly; 300,000 hospitalizations)

Viral, chlamydial, and mycoplasmal diseases

viral upper respiratory infections
viral and mycoplasmal chest colds
viral and chlamydial conjunctivitis
viral and mycoplasmal ear infections
viral gastroenteritis
infectious mononucleosis
herpes zoster infections (chickenpox, shingles)
herpes simplex I (lip) and II (genitals)
cytomegalic inclusion disease (cytomegalovirus infection)
chlamydial urethritis and cervicitis

Fungal, protozoal, and parasitic diseases

tinea ("athlete's foot", "crotch rot", "ringworm", etc.)
fungal infections of the nails
"subclinical" histoplasmosis
"subclinical" toxoplasmosis
lice ("pediculosis")

Men's stuff

adolescent gynecomastia
knee injuries
varicoceles
sports injuries
inguinal hernias
impotence
premature ejaculation
male pattern baldness (bothers some men, doesn't bother others, some men like it)
homosexuality

As always, this is extremely politicized; right or wrong, "ego-dystonic" gay men are not the only people nowadays who seek to become more comfortable with a range of sexual expressions


transvestism ("cross-dressing")
Again, hard to justify as a "disease" though some men may wish to be rid of the compulsion


benign prostatic enlargement
microscopic cancers of the prostate

Women's stuff

fibrocystic diseases of the breast
menstrual iron deficiency anemia
frigidity
menstrual cramps
vaginal infections (candida, trichomonas, gardnerella)
bacterial urinary bladder and kidney infections
atypias of the cervical epithelium
leiomyomas ("fibroids") of the uterus
endometriosis
vomiting of pregnancy
pre-eclampsia
miscarriages
cystoceles
menopausal hot flashes
kraurosis of the vulva
idiopathic hirsutism

Skin diseases

acne
atopic dermatitis ("eczema")
seborrheic dermatitis (dandruff, "oily skin", etc.)
contact dermatitis
drug rashes
miliaria ("prickly heat", "jungle rot", etc.)
warts
seborrheic keratoses
tinea versicolor and ringworm
capillary hemangiomas
dermatofibromas
pigmented nevi ("moles")
lentigos ("moles", "liver spots", etc.)
epidermoid inclusion cysts ("sebaceous cysts")
sun-damaged skin
actinic keratoses

Circulatory system

floppy mitral valve ("Barlow's syndrome")
patent foramen ovale (usually a trivial autopsy finding)
varicose veins

Digestive diseases

dental caries ("cavities")
gum disease
aphthous stomatitis ("canker sores")
reflux peptic esophagitis
hiatus hernias
peptic ulcers of stomach and duodenum
diverticular disease of the colon
functional bowel disease ("spastic colon")
hemorrhoid problems
Gilbert's "disease" (problems conjugating bilirubin)
gallstones

Allergic diseases

food allergies (milk, eggs, peanuts, sesame, wheat, fish, shellfish, etc.)
respiratory allergies ("hay fever", asthma)
poison ivy

Above the neck

functional headaches (muscle spasm, migraine, cluster)
refractive errors, astigmatism
presbyopia
cataracts
conjunctivitis
impacted earwax
otitis externa
presbycusis
serous otitis
otosclerosis
mild perceptual and learning problems

Musculoskeletal problems

low back pain
bursitis
tendinitis
sprains
fractures
ingrown toenails
bunions

Nutritional problems

obesity
"subclinical" folic acid deficiency (major problem, long-neglected)
iron deficiency
"subclinical" iron overload
(??) "functional hypoglycemia" ("idiopathic post-prandial syndrome")
(??) "subclinical" zinc deficiency

Burns

Despite all this, today's North Americans and Northern Europeans (no, not the Himalayan Hunza people; that's a cynical lie) are the healthiest people ever.

WORLD HEALTH

All the diseases listed so far are common all over the world.

Other diseases are very prevalent in some or all of the developing nations.

These are primarily political and economic problems rather than scientific mysteries.

Very common, could be controlled

• Keratomalacia (blindness from vitamin A deficiency)


• Malaria (might be the most prevalent serious disease worldwide)


• Measles (about 700,000 deaths worldwide each year, almost entirely in countries where they do not immunize: Int. J. Inf. Dis. 4: 14, 2000)


• Whooping cough (kills hundreds of thousands of children yearly: Ped. Inf. Dis. J. 16(4S):S85-9, 1997)


• Diarrhea (kills >10,000 babies daily; NEJM 325: 327, 1991)


• Diphtheria


• Neonatal tetanus (still a terrible problem: Bulletin of WHO 76: 161, 1998; there are an estimated 277,000 deaths worldwide each year)


• Trachoma


• Yaws

Very common, less controllable:

• Tuberculosis


• Respiratory infections


• Schistosomiasis


• Hookworm


• Typhoid


• Dengue


• Malnutrition (around 35 million people die of malnutrition yearly)

Very common, less morbidity:

• Polio (thankfully disappearing)


• Hepatitis (A and B)


• Leprosy

The governments of certain "developing" nations actively oppose efforts to control infectious diseases among their poor. They know that these diseases are important in limiting population growth.

During the last few years, the standing of the World Health Organization, a major branch of the United Nations, has deteriorated greatly in the eyes of the medical world. I think a lot of this criticism is misdirected, but the facts are still discouraging. Despite some success against particular infectious diseases, the World Health Organization is helpless to deal with the kleptocratic politics of the poor nations, where governments want their people sick. Instead of focusing on what it does best, it has taken refuge behind a facade of rhetoric ("Health is...." "Health for all by the year 2000", etc.) and grandiose, useless programs. For the sickening facts, see Br. Med. J. 309: 1425, 1491, 1566 & 1636, 1994 and 310: 110 & 178, 1995; Lancet 345: 203, 1995; Lancet 351: 351, 743, 1998. At least the money doesn't seem to be going into the kleptocrats' Swiss bank accounts, which is itself quite an accomplishment.

Today, most health-sector activities in the poor nations are funded by the World Bank, which has taken a hard-nosed attitude in the 1990's and required reform (i.e., the government must adopt policies that encourage free enterprise and a strong economy) and cooperation. See Lancet 351: 665, 1998.

WORDS FOR COMMON AND/OR TRANSMISSIBLE DISEASES: You need to know these terms.

Epidemic: a disease that is widespread in a community of people. (It is often, but need not be, a contagious disease).

Epizootic: an epidemic in a community of animals. (Pronounce it "EPP-ee-zoe-WOTT-ick".)

Pandemic: a worldwide epidemic.

Endemic: a never-ending epidemic.

Infectious disease: one caused (or assumed to be caused) by micro-organisms (the infectious agents) that can be transmitted from creature to creature.

Zoonosis: an infectious disease that people usually acquire from sick animals rather than from other people.

Vector: an organism, usually an insect, that carries an infectious disease from person to person, etc.

Carrier: a person who harbors the infectious agents but has no symptoms.

Reservoir: the place (usually animals or carriers) where an infectious agent lives between epidemics.

HOW COMMON IS A DISEASE?

First, you must define the disease and the population.

Criteria for making the diagnosis of a disease are generally established by pathologists. The autopsy is still ultimate proof of the presence or absence of most diseases.

The population may be all the people in Kansas City, all the pregnant women in Missouri, all the US citizens currently living in Tokyo, all the scleroderma patients attending a certain clinic, etc.

Incidence: the number of new cases during a period of time (generally new cases per 100,000 population per year)

Prevalence: the total number of cases during a period of time (generally cases per 100,000 population)

Obviously, incidence equals prevalence divided by average duration.

OUR FATAL DISEASES YESTERDAY

Our ancestors died of bacterial diseases, smallpox, famine, trauma, and obstetrical catastrophes. Cancer and gout probably followed. Mosquito-borne diseases have also been very important in warmer regions.

The common bacterial infections caused the majority of deaths, young and old people.

Pneumococcal pneumonia was such a common killer of the elderly that it was called "the old man's friend". It did not spare the young, either. Dr. William Osler called the pneumococcus "captain of the men of death". Today penicillin ("the old man's enemy") cures all but neglected cases.

Other gram-positive cocci (staphylococcus, streptococcus) were major killers. They produce a variety of illnesses.

Tuberculosis ("the white plague") killed 1 person in 5. Today almost all cases are curable using drugs.

Syphilis killed 1 person in 5 or even more in the centuries after its introduction, and caused chronic severe pain and/or insanity in many more. Today it is easily cured using antibiotics.

Bubonic plague ("black death") killed half the people in Europe and Asia every few centuries. Now it is easy to cure.

Typhus, a rickettsial disease transmitted by lice, was another highly fatal epidemic disease, especially during wartime. Cholera was yet another major epidemic killer, especially during the 1800's.

Tetanus killed more victims of war wounds than the wounds themselves did. Today almost everybody in the US is effectively immunized against to tetanus toxin. Russell Crowe's character in "Gladiator" reflected after the battle about how many of his men would go on to die of wound infections.

Infantile diarrhea is usually a bacterial disease. It is still a major world-wide killer. All these babies could be saved were it not for political, social, and economic problems.

Influenza, caused by a virus, was another dread epidemic disease. Death is usually due to bacterial superinfection of the damaged lungs.

Yellow fever (caused by a virus) and malaria (caused by a protozoan) were two very important, mosquito-borne killers.

Smallpox, caused by a virus, was the leading cause of death in many countries until vaccination made it preventable.

Most people in the US are immunized: against these diseases, which would otherwise be common:

Diphtheria
Measles
Mumps
Pertussis ("whooping cough")
Rubella ("German measles")
Poliomyelitis
Smallpox (thought to be extinct today)
Tetanus

Several relatively common, noninfectious, non-cancerous diseases that were once often fatal but are now usually cured by surgery.

Abdominal aortic aneurysms
Appendicitis
Berry aneurysms
Benign ovarian tumors
Bleeding peptic ulcers
Cardiac valvular problems
Congenital heart diseases
Dissecting aneurysm
Diverticulitis
Ectopic pregnancies
Gallstones
GI malformations
Intussusception of the bowel
Kidney stones
Obstetrical problems
Strangulated hernias
Volvulus

Without high technology, these would all be important killers once again. (The only exception is smallpox, which seems to be extinct, but could well reappear as a biological weapon.)

OUR FATAL DISEASES TODAY

What kills the two million people who die yearly in the US?

Atherosclerosis

Myocardial infarction ("heart attack") and sudden cardiac death

(These together cause 600,000 deaths per year.)

Stroke (200,000 deaths per year)

Ruptured aortic aneurysm (less common)

(These figures include diabetics, because most diabetics die of atherosclerosis.)

Risk factors for atherosclerosis are:

(1) Elevated serum cholesterol (by far the most important)
(2) Cigaret smoking
(3) High blood pressure
(4) Diabetes mellitus (less important than any of the first three factors)
(5) Lack of exercise (less important than any of the first four factors)
(6) Hereditary differences in the lipoprotein molecules and their receptors, homocysteine metabolism, and the coagulation proteins. Some of these are very important, and are being sorted out.
(7) Obesity? stress? (Whether these are independent risk factors is unclear. You will have to decide for yourself!)

Cancer (over half a million deaths in the US each year)

Any cancer, untreated, will eventually kill the patient.

Approximately 25% of US citizens die of cancer

Slightly more men than women die, since breast cancers are often cured.

See the earlier section on common serious diseases for information about various cancers. Remember lung cancer is now the commonest cancer killer of both men and women. ("You've come a long way, Baby.")

Emphysema and chronic bronchitis (150,000 deaths per year)

Cigaret smoking causes the overwhelming majority of fatal cases.

High blood pressure and heart pump failure (100,000 deaths per year)

High blood pressure promotes atherosclerosis and kidney disease, but it can also kill by causing heart pump failure.

Heart pump failure ("congestive heart failure") may also be due to disease of the valves, anatomical defects, amyloidosis, drugs, virus infections, and so forth.

Alcoholism is the other leading cause of "natural" (?!) death:

Cirrhosis of the liver (70,000 deaths per year from this alone; in the US, alcohol is the usual cause.)

Alcohol is also involved in a majority of homicides, suicides, and accidents.

Pulmonary thromboembolus is primary cause of 50,000 deaths a year. (The source is usually a leg vein, sometimes a pelvic vein.)

Many more patients with serious underlying diseases die with these travelling thrombi as the final mechanism.

Kidney disease (35,000 deaths a year)

Common fatal kidney diseases include chronic glomerulonephritis, chronic interstitial nephritis ("pyelonephritis"), and adult polycystic kidney disease.

Diabetes mellitus, amyloidosis, systemic lupus, and bad high blood pressure are other common causes of end-stage kidney disease.

Alzheimer's disease (including "senility") causes many deaths, usually through bacterial-aspiration pneumonia.

Bacterial and aspiration pneumonias are common final mechanisms of death in many debilitating diseases.

Today, the pneumonias seldom kill a previously-healthy young person.

Acquired Immune Deficiency Syndrome (AIDS)

In some communities, AIDS remains a leading cause of death.

Unnatural deaths:

Homicides (around 30,000 per year)

Suicides (true number unknown, estimates give it around 50,000 per year)

"Accidents" (around 100,000 per year)

When pathologists speak of the manner of death, we mean "natural", "homicide", "suicide", or "accidental". We may also conclude, after autopsy, that the manner of death is "undetermined".

Iatrogenic disease is disease caused by medical diagnosis and/or treatment. It is epidemic, though deaths are usually listed under the patient's disease and often would have occurred anyway. (Classical scholars call it "iatrogenous disease"....) For the disturbing Harvard study, see NEJM 324: 307 & 377, 1991.

What kills young people in the US?

"Before birth":

An unknown percentage (at least 31%, maybe more -- NEJM 319: 189, 1988) of fertilized eggs fail to implant or are lost before pregnancy is recognized.

Around 1 out of every 6 known implantations is followed by spontaneous miscarriage.

There are around 1.5 million legal abortions performed in the US yearly. (Contrast this to large areas where both contraception and abortion are illegal, and where illegal abortion is the leading cause of death in women aged 15-39: Br. Med. J. 300: 1705, 1990.)

You will have to decide for yourself what all this means.

Under one year: Prematurity and birth defects

Around 1.3% of US newborns die from these causes. This is pretty good; only a few nations with fewer % poor do better.

Mysterious "sudden infant death syndrome" kills around 0.5% of infants during the first year of life. See below.

Ages 1-19:

Males:

(1) "Accidents" (around 8000 / year)

(2) Homicide (around 2500 / year)

(Homicide is extremely common in the age 10-20 range in certain U.S. communities; JAMA 267: 2905, 1992)

(3) Suicide (around 1700/year)

(4) Cancer (around 1200/year)

Females:

(1) "Accidents" (around 4000 / year)

(2) Cancer (around 1000 / year)

(3) Homicide (around 700 / year, double the suicide rate)

Child abuse and neglect causes some deaths among children. The true prevalence is unknown and is controversial -- at least some are overlooked ("accidents" or "sudden infant death syndrome"). Likewise, the incidence of infanticide in the developing nations is unknown, but is probably high.

Ages 20-39:
Males:

(1) Accidents (around 20,000 / year)

(2) Suicide (around 9000 / year)

(3) Homicide (around 8000 / year)

(4) Heart disease, followed closely by cancer and then HIV infection

Females:
(1) Accidents (around 6000 / year)

(2) Cancer (Around 6000 / year)

(3) Heart disease (around 2800 / year)

(4) Suicide, followed closely by homicide and HIV infection

Natural death in young athletes:

• Coronary artery atherosclerosis (think of hereditary cholesterol problems; marathon runners' immunity to atherosclerosis is a lie)


• Coronary artery malformations


• Berry aneurysms


• Hereditary hypertrophic cardiomyopathy


• Right ventricular dysplasia (Am. J. Med. 89: 588, 1990)


• Conduction system problems (WPW, long QT syndrome, Brugada)


• Cocaine use


• Electrolyte problems (i.e., diuretic abuse)


• Myocarditis

The average American's chances of being killed by (Nature 367: 39, 1994):

motor vehicle accident... 1 in 100
murder... 1 in 300
house fire... 1 in 800
firearm accident... 1 in 2500
electrocution... 1 in 5000
passenger plane crash... 1 in 20,000
flood... 1 in 30,000
tornado... 1 in 60,000
fireworks... 1 in 1 million
botulism... 1 in 3 million
asteroid or comet impact with earth... 1 in 3000 to 1 in 250,000

LIFESTYLE-RELATED DISEASES:

Today's deadly diseases in the US are largely lifestyle-related. (This is one factor that contributes to physicians' dissatisfaction with their work!)

Alcohol abuse and nicotine addiction are grave public health problems. Use of certain of the illegal drugs (amphetamine, cocaine, heroin, phencyclidine, others) is clearly harmful.

Contrary to what you have been told by doctor-bashers, the prevalence of alcoholism and drug addiction among physicians is substantially lower than among their non-physician peers. However, doctors do have an unfortunate tendency to prescribe mind-altering substances for themselves. Don't do this. See JAMA 267: 2333, 1992.

Sexual promiscuity (homosexual, heterosexual) causes many health problems.

Obesity and lack of exercise probably contribute to ill-health.

Americans tend to eat too much salt, saturated fat and cholesterol, too many calories, and too little fiber. Sucrose (cane sugar) is bad for the teeth.

Sunlight is the principal cause of all three common skin cancers, as well as the cancer that arises within the adult eye. (Sunlight also helps activate vitamin D, but vitamin D supplementation of food has apparently eliminated our need for sunlight.)

Some food additives that make some people sick are tartrazine yellow (dye), monosodium glutamate ("Chinese restaurant syndrome"), wasabi (horseradish served with sushi, the "Japanese restaurant syndrome"), and sulfites ("salad-bar asthma").

Despite the claims of "alternative medicine", the following are probably not significant health problems. (Let us know if you have additional facts about these.)

• lack of sunlight (where there are other ways to get vitamin D)


• refined sugar


• white flour


• coffee and tea


• cow's milk


• Pasteurized milk


• Bovine growth hormone


• cooked ("dead") food


• antiperspirants


• fluoridated water


• tap water


• food preservatives


• pesticide residues


• immunizations


• subclinical vitamin and mineral deficiencies (except folic acid in junk-food-only folks and folks who need more because of kinks in their metabolisms, and vitamin D in old folks)


• amygdalin ("laetrile", "vitamin B-17") deficiency


• pangamic acid ("vitamin B-15", usually glycine or sugar) deficiency


• toxic bowel settlement ("removed only at enema parlors")


• spinal subluxations (undetectable except by traditional chiropractors)

INHERITED DISEASE AND BIRTH DEFECTS

Commonest serious Mendelian genetic diseases:

• Familial hypercholesterolemia ("hyperlipidemia type II") (?? 1/200)


• Polycystic kidneys (1/800 adults)


• Fragile X (1/1500 men)


• Cystic fibrosis (1/1600 white kids)


• Sickle cell disease (1/1600 black kids)


• Von Recklinghausen's disease (1/2500 people)


• Tuberous sclerosis (?? 1/1000)


• Duchenne's muscular dystrophy, "Jerry's kids", 1/3500 boys)

Many genetic syndromes are much more prevalent within particular ethnic groups. No race is "superior". Here are a few to remember:

• Alpha-thalassemias and sickle-thals (Blacks)


• Beta-thalassemias (Mediterraneans)


• Gaucher's disease (Jewish people)


• G-6-PD deficiencies (a mild Black form, a severe Mediterranean form)


• Hemoglobin C and sickle-C diseases (Blacks)


• Hemoglobin E disease (Vietnamese)


• Hereditary spherocytosis (Scotch-Irish)


• Joseph Disease (Portuguese)


• Pyruvate kinase deficiency (Amish)


• Tay-Sachs disease (Jewish people)

While we're here... I have often questioned the value of declaring the person's race at the beginning of the case presentation. I give my "race" as "human", and believe that everybody else should, too. Compared with Euro-Americans, Afro-Americans have substantially more deaths due to high blood pressure, plasma cell myeloma, and prostate cancer, and substantially fewer deaths due to malignant melanoma; they also have far less osteoporosis and testicular cancer.

The suicide rate among black men in the US is also far lower than among white men. For a review, see Lancet 351: 934, 1998.

The commonest chromosomal syndromes are Klinefelter's (XXY; 1/850) and Down's syndromes (trisomy 21; maybe 1/1000). Turner's (XO) and "supermale" ( XYY, a curious subject) are slightly less common.

The commonest catastrophic birth defects are neural tube defects (bad "spina bifida", etc.; 1/500 births) and cerebral palsy (maybe 1/400).

DREAD DISEASES OF YOUNG ADULTS:

Several common, chronic diseases that can be really bad and that begin during young adult life are listed here, with their approximate prevalence among young adults.

• Alcoholism (8%)


• Ankylosing spondylitis (0.1%)


• Berry aneurysm rupture (0.2%)


• Major mood disorder ("manic-depression", 0.7%)


• Multiple sclerosis (0.1%)


• Regional enteritis (0.1%)


• Rheumatoid arthritis (3%)


• Schizophrenia (1%)


• Systemic lupus erythematosus (0.5%)


• Ulcerative colitis (0.3%)

"NEW DISEASES" (unknown, rare, or seldom recognized a few years ago):

• Alexithymia


• Angioimmunoblastic lymphadenopathy


• Anticardiolipin antibody ("lupus anticoagulant") disease


• Asperger's (high-functioning autism, great at science and math, much difficulty learning social skills)


• Biliary sludge


• Branhamella infections


• BRCA1 anti-oncogene deletion syndrome
• Brugada's: sudden death in young men with a characteristic EKG


• Carbohydrate craving syndromes


• Chlamydia TWAR, the asthma bug


• Chlamydial sexually transmitted disease


• Chronic infectious mononucleosis


• Cryptosporidiosis


• Dysplastic nevus syndrome


• Esophageal chest pain (vascular spasm: -- Gastroent. 116: 28, 1999; Ann. Int. Med. 124: 1008, 1996)


• Facet syndrome (back and neck pain)


• Familial hypocalciuric hypercalcemia


• Fetal alcohol syndrome


• Fetal tobacco syndrome


• Fibromyalgia syndrome ("fibrositis", "pain modulation syndrome")


• Floppy mitral valve


• Food allergies (the more subtle manifestations)


• Fragile X syndrome (hemizygous, heterozygous)


• Helicobacter infections


• Herpes simplex II


• Homocysteine problems (atherosclerosis, thrombosis)


• Human papillomavirus sexually transmitted disease


• Hypercoagulability genes (antithrombin III and protein C and S deficiencies, V-Leiden)


• Hürthle cell adenoma of the kidney


• Iatrogenic hyponatremia (Br. Med. J. 304: 1218, 1992)


• IgA nephropathy


• Immotile cilia syndromes (Kartagener's, etc.)


• Interstitial cystitis ("Hunner's ulcer")


• Iron overload syndromes


• Job's hyper-IgE syndrome


• Kawasaki disease


• Legionnaire's disease


• Li Fraumeni anti-oncogene deletion syndrome


• Long QT (about 4000 deaths per year in the US alone)


• Lyme arthritis


• "New" complications of chronic hemodialysis (amyloidosis, kidney cancer)


• Non-alcoholic steatohepatitis


• Non-polyposis familial colon cancer


• Obsessive-compulsive problems (once "rare")


• Parvo 19


• Persistent pulmonary hypertension of the newborn


• Post-streptococcal behavioral changes ("PANDAS")


• Renal tubular acidosis


• Retrovirus infections (AIDS, epidemic leukemia, etc.)


• Severe acute respiratory syndrome (coronavirus) / hantavirus pneumonia
  
• SAPHO (acne, pustules within bones, odd bony overgrowths especially on the chest joints)


• Seasonal affective disorder


• Sjogren's encephalopathy


• Sleep apnea


• Sleep-related eating disorders


• Sulfite allergy ("salad bar disease")


• Thrombophilias (inherited hypercoagulable blood; several dominant genes)


• Transient stress lymphocytosis (wasn't on the books, but I think it was generally known)


• Vulvar vestibulitis syndrome ("the pain isn't sexual, the sex is painful"; I think it's an organic pain syndrome -- until recently they got sent to the psychiatrist)

"NON-DISEASES" (i.e., named entities that produce no morbidity or are beneficial)

• Absent deep tendon reflexes, many other "neuro" curiosities


• Birthmarks (most types), cherry angiomas


• Carbon pigmentation of the lung ("uncomplicated black lung")


• Cardiac rhythm disturbances (certain types)


• Carrier states, including thalassemia minima and most thalassemia minors


• Certain inborn errors of metabolism (some are even "longevity genes")


• Exercise-related "abnormalities" ("athlete's heart", lab test changes)


• Ectopias (Fordyce granules, etc.)


• Freckles, lentigos, common nevi, most anisocoria and vitiligo cases, morphea


• Hyperlipidemia type IV ("isolated hypertriglyceridemia")


• Macroamylasemia (idiopathic type), many other lab curiosities


• Medial calcific sclerosis of the arteries ("Monckeberg's")


• Minor malformations (torus, Darwin's tubercles, fused toes, many others)


• Nail anomalies (most)


• Orthostatic proteinuria, thin-GBM non-disease


• Physiologic jaundice of the newborn, "Gilbert's" bilirubin conjugation defects


• Pigments from medications (melanosis coli, argyria) or food (carotenemia)


• Soldier's plaque of the epicardium


• Sugar-icing of the peritoneal surfaces


• Tinea versicolor, other trivial infestations


• Tongue anomalies: most geographics, hairys, rhomboids, and scrotals

Some of these might be considered minor cosmetic problems, or patients may actually like them.

EASY-TO-MISS DISEASES

Primary care is the pinnacle of medical practice because the physician must constantly be asking, "What is the WORST TREATABLE thing this COULD POSSIBLY be?" Then the physician must rule this out (or in).

Here's my list of easy-to-miss, easy-to-treat, deadly-if-untreated diseases.

• addisonism (adrenal cortical insufficiency; several causes)


• arsenic poisoning


• B₁₂ deficiency (pernicious anemia, fad diets)


• bacterial endocarditis


• bacterial meningitis (easy to miss in the very young)


• Behcet's


• carbon monoxide poisoning (bad home heater; miss this and the whole family dies)


• carcinoid syndrome


• cerebrospinal fluid leak


• compartment syndrome (you won't get another chance...)


• cryoglobulinemia syndromes


• cushingism (adrenal cortical hyperfunction; several causes)


• gas gangrene / flesh-eater streptococcus (you won't get another chance...)


• hemochromatosis


• hereditary angioedema


• hyperthyroidism (especially its atypical presentations)


• hypopituitarism (don't miss any form, including adult growth hormone deficiency)


• hypothyroidism


• insulinoma


• lead poisoning


• long QT


• Lyme disease


• manganese poisoning


• meningococcal infection


• neurosyphilis


• normal pressure hydrocephalus


• osteomalacia / vitamin D deficiency (especially with today's fad diets)


• pheochromocytoma


• polyarteritis nodosa / Churg-Strauss


• porphyrias (a whole bunch of them)


• relapsing polychondritis


• renovascular hypertension


• Rocky Mountain spotted fever


• sarcoidosis


• sleep apnea


• sporotrichosis


• Stevens-Johnson syndrome


• temporal arteritis


• thallium poisoning


• tuberculosis, especially in the meninges


• Wegener's granulomatosis


• Whipple's (especially its atypical presentations)


• Wilson's copper overload

DISEASES WE SKIP

In this course, we do not discuss certain functional medical problems (i.e., those that lack any known anatomic correlate). However, it is obvious that physiologic defects are essential to these processes.

• Addictions (alcoholism, heroin, cocaine, nicotine, etc.)


• Functional obesity, anorexia nervosa, bulemia


• Schizophrenia, autism, major affective disorders


• Idiopathic epilepsy, narcolepsy, sleep apnea, trigeminal neuralgia


• Panic disorder, agoraphobia, globus hystericus


• Conversion reaction, obsessions and compulsions


• Attention disorder ("hyperactive child"), learning and reading problems


• Some personality disorders and gender identity problems, alexithymia


• Phantom limb phenomenon, causalgias


• Functional headaches (tension, migraine, cluster), benign familial tremor


• Normal pressure hydrocephalus, pseudotumor cerebri


• Functional bowel syndrome ("spastic colon"), "colonic inertia" (slow-transit-time constipation), menstrual cramps, bashful bladder, premenstrual syndrome


• Proctalgia fugax, prostatodynia, nocturnal leg cramps


• Fibromyalgia syndrome ("fibrositis")


• Orthostatic proteinuria, intermittent idiopathic hematuria


• Idiopathic paroxysmal atrial tachycardia, other arrhythmias, heart blocks


• Idiopathic infertility, other sexual problems


• Movement disorders (torticollis, Tourette's, blepharospasm, myoclonus, "restless legs")

Other important medical problems are largely mechanical and you will learn about these on your rotations.

• Burns and their complications


• Intertrigo, decubiti (bedsores), stercoraceous ulcers, fecal impaction


• Functional heart murmurs


• Cleft palate, pilonidal cysts


• Hernias, cystoceles, rectal and uterine prolapses


• Muscle strains and sprains, tendinitis, bursitis, carpal tunnel syndromes


• Specific fractures and their complications


• Dislocations, subluxations, compartment syndromes


• Nerve compressions


• Bunions, ingrown toenails, ganglion cysts


• Knee problems (torn menisci, torn ligaments, etc.)


• Other non-traumatic joint problems (congenital hip dislocations, Legg-Calve-Perth's, Osgood-Schlatter's)


• Back and neck problems (curvatures, strains, herniated nucleus pulposus, cervical spondylosis)


• Obstetrical problems (cervical incompetence, disproportions, malpositions, placenta previa, abruption of the placenta)


• Eye problems (presbyopia, cataracts, glaucoma, retinal detachment, strabismus, keratoconus)


• Ear problems (otitis externa and media, Ménière's, Báràny's, otosclerosis, impacted cerumen)

A few other important entities usually fall outside the domain of anatomic pathology:

Porphyrias and other inborn errors of metabolism have few or no anatomic changes, and we will discuss these only briefly. Retinitis pigmentosa is an important group of degenerative disorders of the retina, but pathologists almost never see them, since they are not biopsy-diseases.

Wolf-Parkinson-White syndrome, blocks (bundle branch, Winckebach's, Mobitz II, Stokes-Adams attacks, etc.), channelopathies like Brugada's and long QT, and a host of other cardiac conduction-rhythm problems are diseases for electrocardiographers, not pathologists.

Transient ischemic attacks of the brain ("little strokes"), amaurosis fugax, and related phenomena leave no anatomic traces.

The anaphylactic, vasovagal, and vagovagal varieties of shock can cause death with little or no anatomic change. So can postural asphyxias ("swallowing the tongue", etc.)

The anatomic pathology of cerebral concussion is unknown.

RIGHT TREATMENT, WRONG REASON

"Science is self-correcting". In medical school, I was taught silly mechanisms ("nitrates dilate your calcified coronary arteries!") for the following treatments, which actually work well but by a different mechanism:

• nitrates for angina pectoris (did anybody ever really believe that nitroglycerine dilated all those fibrotic and calcified coronary arteries?!)
• bismuth for peptic ulcer and gastritis (the "antiacid and coating agent" actually kills the bacteria)
• selenium ("blue shampoo") for dandruff and seborrhea (various fanciful mechanisms of action were discarded when we figured out that it really kills the fungi that cause dandruff)
• nitroprusside for hypertensive crisis (breaks down into the previously-unknown endothelially-derived relaxation factor)
• salicylazosulfapyridine for ulcerative colitis (watch for this one; it's an antibacterial that probably kills the bacteria that cause ulcerative colitis; currently "believed to work by inhibiting prostaglandin production and preventing inflammation", though it isn't in use for anything else)
• interferon for Kaposi's "sarcoma"; in the early AIDS era, clinicians went gah-gah over "probable mechanisms of action against this cancer"; now it's clear that Kaposi's is not cancer at all, but a viral infection, and interferon is an anti-viral compound. Ditto interferon and hairy-cell leukemia.

MORE WORDS ABOUT DISEASES

Symptoms: what the patient tells you, the physician.

Signs: what you, the physician, discover on physical exam and special studies, by yourself or with help. Means the same as findings.

Lesion: any unit of abnormal anatomy (less often, abnormal chemistry or an abnormal molecule)

Morphology: the anatomic lesion(s)

Etiology: what causes the disease. A noun or nouns. If it's external, it's called the etiologic agent. The etiology of many diseases is unknown.

Pathogenesis: how the etiologic agent causes the disease. A short story that usually includes "many of the steps are presently unknown".

Pathognomonic: a sign or group of signs that occur in only one disease. Same as diagnostic (of).

Prognosis: how the patient can realistically expect to do.

Syndrome: A group of symptoms and/or signs that tend to run together but may be caused by any of several diseases

THE GREATEST MISERY

Which diseases cause the most overall suffering and time lost from work prior to old age? It is probably a near-tie:

• Alcoholism (self, family member)
• All other psychiatric disease together (schizophrenia, mood disorders, neurosis)
• Musculoskeletal disorders (arthritis, low back pain)

MALE:FEMALE RATIOS

Many diseases clearly occur more often in one sex or the other.

The reasons for this are seldom known, but will probably be discovered. (For example, pre-menopausal women are immune to South American blastomycosis because estrogens cause the fungus to revert to hyphal form, which is easily killed by the body.)

These rules of thumb work most of the time:

Women are more likely to get any disease in which autoimmunity is believed to be an important mechanism (except diseases linked to a particular class I HLA molecule, i.e., ankylosing spondylitis and its family).

Women also are more prone to develop significant osteoporosis.

Men are more likely to get all the other diseases.

THE MOST INTERESTING DISEASES

This is a matter of opinion. You may decide the psychiatric disorders are the most interesting.

Especially intriguing are treatable organic diseases that affect the mind. Remember these before you commit your patient to psychotherapy or a life in custodial care!

• Adrenal gland problems (too much or too little cortisol or catecholamine)


• Brain infections (remember cryptococcus, herpes simplex I, Lyme disease, HIV)


• Brain tumors (especially meningiomas) and many other brain diseases


• Brucellosis, other chronic infections


• Drugs (know atropine, digitalis, methyldopa, reserpine, drugs of abuse)


• Epilepsy (especially temporal lobe problems and psychomotor seizures)


• Hashimoto's encephalopathy


• Hypoglycemia (early type II diabetes, insulin shock, tumors, functional)


• Immunologic disease (systemic lupus, IgE-mediated allergies)


• Infectious mononucleosis (Epstein-Barr, cytomegalovirus "mono")


• Osteomalacia (not all of your "total body pain" patients have fibromyalgia....)
• Parathyroid disease (hypercalcemia, hypocalcemia), other calcium problems


• Poisoning (especially mercury)


• Porphyrias (especially acute intermittent)


• Potassium problems (too much, too little)


• Sensory deprivation (is your patient blind? deaf?)


• Syphilis ("general paralysis of the insane") and perhaps Lyme disease


• Thrombotic thrombocytopenic purpura


• Thyroid problems (too much thyroid hormone, or too little)


• Vitamin B₁, B₃, and B₁₂ deficiencies


• Wilson's disease (copper disposal problem)

CULT DIAGNOSES ("imaginary diseases")

"A court of law is not a good place to try to get at the truth." Certain "cult" diagnoses have had a devastating impact on both their "victims" and those around them. People with emotional problems typically feel chronically unwell. (The mainstay of therapy is to learn new living skills to replace those that were once required to survive in an abusive home.) However, once such a person self-diagnoses or is diagnosed as having a "cult" diagnosis, he/she gains "victim" status, will make absurd demands on others, and will get sicker and sicker.

Multiple chemical sensitivities is seen almost exclusively in survivors of real child abuse. Strangely, most or all synthetic chemicals cause symptoms (but no objective signs), exactly at the threshold at which the chemical can be smelled. Natural chemicals do not have this effect. The obvious conclusion is the correct one. Tell such a person that an odor is synthetic (even carbon dioxide), and it will produce symptoms. Victims typically try to force everyone around them not to use cologne or deodorant, etc., etc. If a schoolchild is designated as "victim", all the teachers and other kids are affected. And so forth.

The false memories syndrome ruined thousands of lives for the falsely-accused before society finally wised up. Rather than learn new methods of coping with adult life, emotionally-disturbed people were told instead that they were horribly scarred by (probably-imaginary) forgotten sexual abuse and/or satanic cult exposure and/or alien abduction. Again, the cult keeps people sick.

There are certain to be more cults like this in the future. As physicians, you will discover that if you suggest to someone that a particular symptom will develop, it will. This makes these iatrogenic diseases.

TREATING DISEASE

We are healthy because of good food, good sanitation, adequate living space, public health programs, and a good medical system for treating diseases and injuries. (It is hard to say which of these is most important.)

Some diseases can be cured.

Examples include surgical diseases (localized cancers, appendicitis, hernias, gallstones, etc.), and bacterial and parasitic diseases.

Surgery became practical with antisepsis in the later 1800's, while the antibiotics came into use in the 1940's. Before this, the history of therapeutics was essentially the history of quackery and iatrogenic disease.

Most other diseases are not curable, but can be treated.

Treatments that work well are generally simple once you understand the pathology. Treatments that don't work well are generally quite elaborate. (One notable exception is chemotherapy for a few cancers, principally those that occur in young people.)

Again, most effective treatments are of relatively recent origin.

Your patients may be self-conscious about disease that cannot be treated, and cannot be hidden.

Other people tend to shy away from the person who's visibly different.

Not for sissies, but the best, and easiest, ice-breaker when the problem cannot be hidden is for the patient to draw attention to the problem. Decorate your wheelchair (movie, "Silver Bullet"). Put plastic flowers on your crutches. "Do you like my birthmark [grin]? Feel how rough it is!" "Every hair fell out of my body when I was only six!" "A bear did that to me [chuckle]." "I'm a hobbit." Choose a nickname ("Folks call me 'Patch' / 'Spot' / 'Eraser Man'!")

The practice of medicine in the U.S. has become so corrupted by big-money and big-egos (plus an occasional bit of sheer stupidity) that Americans now trust their lawyers more than their physicians, particularly to explain all the options truthfully and to act according to their wishes (NEJM 330: 223, 1994).

I would like you to help change this back. I will give you the knowledge and the power to reason; you need to find the integrity within yourselves.

The medical care that people receive in the US is high-quality but very expensive. Often the benefits of treatment are obvious, often they are not. Our society has decided to make it hardest for the working poor to obtain basic care, and rations the care for those with access by "managed care". Expect this to change.

Health care costs total around 12% of our gross national product. Remember these equal health care incomes. Physician's bills make up around 30% of this. In 1992, we spent $800,000,000,000 on health care.

The British health care system generates only half the costs (and half the incomes) of our health care system. The British seem to be just as healthy as we are.

It is commonplace for the hospital bill for a profoundly brain-damaged premature baby to total $100,000 or more. (By comparison, the amount spent to save each otter after the Exxon Valdez oil spill was a mere $80,000: Science 254: 1596, 1991.)

The average cost to the family of a child who has died of leukemia (not counting the portion that their insurance pays) is $38,000. (There are around 12,000 new cases of childhood leukemia per year; around half of them get cured, the other half die.)

In mid-1986, the average AIDS victim lived 160 days with the disease, and died with medical bills totalling $140,000. A lot has changed since then, but the cost of treating ten American AIDS victims exceeds the total health care expenditures of several developing nations with millions of sick people.

There are now 10,000 people in the United States in irreversible comas. There are many thousands more with profound mental impairments or "locked in". (All these are unkindly called "vegetables"; "apallic" means no working cortex.) All would die quickly without continuous medical care, and someone pays $130,000 per patient per year (Br. Med. J. 301: 1094, 1990).

Today, the usual cause of a well-to-do US family's being reduced to poverty is medical bills for the care of one member.

Around 28 million US citizens have little access to primary health care because they have neither insurance nor welfare.

One factor that makes health care more expensive in the US is large awards in medical malpractice cases. The average award today is over one million dollars.

It is probably inevitable that any system of health care distribution will contain perverse incentives (Sci. Am. 269(1): 24, July 1993) either to overtreat-overcharge (fee-for-service, defensive medicine) or to undertreat (HMO's/managed care, British socialized medicine).

Disease can ruin the quality of life for a person. Most of us physicians find it hard not to treat disease under any circumstances.

Managed care saved the health care system in the mid-1990's. Managed death is next. Most states now have a Natural Death Act, reflecting a world-wide movement. (Of course, you don't stop treating all patients who say they want to die.) Right or wrong, by the time you are in practice, active euthanasia, under some circumstances, will almost certainly be legal throughout most, if not all, of the U.S.

Active euthanasia is already a fact of life in most countries (for example, Hastings Center Reports 22(6): 3, Nov.-Dec. 1992), though it remains illegal. French physicians talk freely about euthanizing babies when there is profound neurological damage (Lancet 355: 2112, 2000). The Dutch legalized active euthanasia experience: Lancet 338: 669, 1991. Euthanasia was lately (1997) legal, with some controls, in parts of Australia (NEJM 334: 326, 1996). However, this was reversed on political pressure. Oregon's "Ballot Issue 16" succeeded in 1994 and was strongly supported by the Federal appeals court (i.e., the government has no reason to interfere with a terminally-sick person's desire to die comfortably; this thinking would put active euthanasia on a par with legal abortion). Colombia legalized it in 1997 (Br. Med. J. 3134: 1852, 1997), the same month that the Supreme Court decided that physician-assisted suicide was not a constitutional right, but that the states could decide (Washington vs. Glicksberg, Vacco vs. Quill). Oregon made it legal in 1997 (NEJM 340: 577, 1999), and it has had a major impact on terminal care, not so much that assisted suicide is being carried out but that physicians have educated themselves about things they can do instead (JAMA 285: 2363, 2001; JAMA 288: 91, 2002 is a good "what to do when..." article). The reason people choose it is mostly out of fear of losing autonomy and/or bowel/bladder control (NEJM 342: 598, 2000). Suicide and assisting suicide for an altruistic motive have always been legal in modern Switzerland, and the Swiss will probably soon legalize active euthanasia (Br. Med. J. 321: 271, 2003). Active euthanasia used to bother me some. However, it is now pretty clear that a solid majority of the American public wants to allow active euthanasia in certain incurable-disease situations: (NEJM 326: 197, 1992; JAMA 267: 2658, 1992; according to the JAMA, several mostly-pro-life demographic segments that one would expect to oppose the idea actually support it strongly). In 1992, a state referendum (Washington Initiative 119) failed; exit polls showed it failed only because voters thought the particular ballot proposal lacked sufficient controls. Both the physicians and the public in Jack Kevorkian's Michigan seem to strongly prefer legalization over an explicit ban (NEJM 304: 303, 1996). The British overwhelmingly favor active euthanasia in cases of intractable suffering and useless life: Br. Med. J. 305: 728, 1992. Even the British Medical Journal, not noted for its radical editorials, called Jack Kevorkian a "hero": Br. Med. J. 312: 1431, 1996. The Netherlands experience, and a little number juggling for the US, indicates that physician-assisted suicide won't be a huge money-saver for the public (NEJM 339: 167, 1998) -- implicit is the reassurance that it won't do major harm to health care incomes. More from the Netherlands: NEJM 342: 551, 2000. Mount Sinai euthanasia survey: NEJM 338:1193, 1998. According to this anonymous poll, it's not as widespread in the US as you might think. Only about 10% of oncologists say they have performed physician-assisted suicide (Ann. Int. Med. 133: 527, 2000)

New definitions of death will focus on permanent loss of higher cortical functions and allow a physician to pronounce a patient dead while the heart is beating (Hast. Cent. Rep. 23(4): 18, 1993; I said years ago this would happen as the need for health care rationing became obvious). For some reason (not physicians' incomes, surely), the AMA still goes gah-gah over both active euthanasia and physician participation in capital punishment (JAMA 270: 365, 1993, though abortion for convenience isn't a problem), but the AMA is now willing to publish neutral articles on what a physician should do if asked for active euthanasia (accompanied, of course, by reaffirmations of its opposition to active euthanasia; JAMA 270: 870, 874 & 875, 1993). The New England Journal no longer subscribes to the anti-euthanasia taboo: NEJM 334: 1374, 1996.

Were I to request active or passive euthanasia, or end my life to escape the ravages of disease or injury (any of which I might at some time do), I would want at least some of the money that would have been spent on my care to go to help poor children who would otherwise not have a chance in life. I suspect that most decent people think similarly, and a few physicians are finally finding the courage to say as much in public (South Afr Med. J. (!): 82: 35, 1992).

Today's medicine causes health problems. Much of this is unavoidable, and is even expected. Iatrogenic ("doctor-caused") problems include:

• complications of surgery, drugs, radiation, and other therapies
• expected and unexpected effects of invasive diagnostic procedures
• patient misunderstandings and stigmatization
• "economic morbidity" to patients and their families

In considering today's epidemic of iatrogenic disease, we must remember that all the writings of Hippocrates ("First Do No Harm") do not contain a single remedy specific for a particular disease.

It is a fact that patients almost always misrepresent what has happened between them and any physician. (For example, I have never heard a physician tell a patient how long he or she would live.) Remember this when you take patient histories, and when you hear "testimonials" (good or bad).

UNCONVENTIONAL TREATMENTS

Many sick people seek treatment from outside the hated "medical establishment". They may choose from a wide range of unconventional healers.

Many people claim that they have been healed by unconventional means. You will have to form your own opinion about each case.

Rheumatoid arthritis, regional enteritis, multiple sclerosis, and warts often seem to respond remarkably well to spiritual healing. I know no naturalistic explanation for these cases, though there might be one, and there are no "placebo-controlled studies".

If you investigate other cases thoroughly, you will most often discover that the patient never had the disease, or was cured by conventional means, or had a self-limited disease, or still has the disease.

Denial of illness is characteristic of many sick people. Remember also that some people are under great pressure to say they have been healed "spiritually". Many people still believe that serious disease is a punishment for extraordinary sinfulness (their own, their parents').

As a lawyer, Ms. Rodham-Clinton wrote a brief arguing that the state could force parents who believed their child's cleft palate was "God's punishment" to have it fixed anyway. The Republicans (convention, 1992) cited this as proof she was "anti-family".

When you read articles pointing out that sick people who attend church seem to do better than those who don't, bear in mind that those attending church are perhaps not so sick and/or have a better support system.

Most clergy are happy to work with physicians, and a spirit of mutual respect usually prevails.

Two references on "commercial" (?) faith-healing:

Dr. William Nolen's Healing: A Doctor in Search of a Miracle, 1974. Dr. Nolen, a Christian, personally investigated Katheryn Kuhlmann, occultist Norbu Chen, and the Filipino psychic surgeons. Dr. Nolen saw no evidence of any miracles. All but Kuhlmann were blatant and shameless frauds.

Professional stage magician James Randi's personal investigation of TV faith-healers appears in The Faith Healers, Buffalo: Prometheus Books, 1987. Mr. Randi describes many fraudulent practices. (For me, the most damning of all the observations is that the "televangelists" never approach or televise the members of the audience that are truly and visibly sick -- multiple sclerosis, cerebral palsy, visible tumors, obvious deformities, etc.)

People in the US spend over ten billion dollars per year on the unproven remedies of alternative medicine. This is several times greater than the total spent on medical research.

Almost without exception, health-care providers who say they use alternative techniques have never tested their methods by honest, controlled experiments. Instead, they have six standard excuses.

(1) "Our methods are harmless and pleasant."

(2) "Our methods are less expensive than the AMA's."

(3) "Our methods are spiritual and/or cannot be explained."

(4) "We will never treat individual 'whole persons' as statistics."

(5) "The methods of science are invalid (Einstein's relativity, Heisenberg's uncertainty, 'Postmodernism', etc.)"

(6) "We don't have any money for research." (!?!)

Alternative practitioners make a great show of loving their patients. They are also much more likely than faith-healers to attack the characters, motives, and skill of honest physicians.

NOTE: In 1986, the average yearly income for a chiropractor, after taxes and expenses, was $116,000.

Attacks on genuine science come from both the screwball right and the screwball left, and are hallmarks of both. Now that the left-wing social agenda (i.e., massive government redistribution of wealth and opportunity) is overwhelmingly unpopular around the world, left-wing nuts in "academia" have little to do except bad-mouth science, which nobody understands anyway. For example, in 1995, the $5.3 million dollar Smithsonian "Science in American Life" exhibit omitted all reference to the space program and the transistor in favor of an emphasis on underrepresentation of women and minorities in science, and how research is often driven by the corporate profit motive instead of pure altruism (Nature 374: 207, 1995; and you thought Marxist ideology was dead?) A real scientist on the project complains about domination of the whole project by left-wing "social scientists and pseudoscientists who had no idea how science really works."

Evidence that spiritual healing or alternative remedies are ever effective remains anecdotal.

But right or wrong, spiritual healers and alternative medical practitioners have a tremendous impact on your patients' perceptions of disease and medical doctors.

In particular, be aware that some of your most helpless patients will have their therapeutic and pain medications withheld by families who have bought into "spiritual" ("Christian" or "New Age") or "alternative healing".

As of this writing, the Office of Alternative Medicine (now the National Center for Complementary and Alternative Medicine), established at the NIH for political reasons, isn't inspiring much confidence (Sci. Am. 269(3): 39, Sept. 1993; JAMA 280: 1553, 1998)

HOLISTIC MEDICINE

Classical pathology describes discrete diseases and this enables us to treat patients effectively. There actually are different diseases that are best treated by different methods.

Offering a simple-minded explanation and a "safe natural treatment" for the "whole" of disease (or to strengthen the "whole" patient) are standard ploys of the medical quack.

So is the meaningless charge that "AMA doctors don't understand health".

Do not confuse the slogans of quackery with the methods all physicians use to understand and help their patients as people.

The relationship between "stress" and disease remains poorly understood. (All about stress: JAMA 267: 1244, 1992, for physiologists).

In many animal models, stress seems to help cause specific diseases, but in many others, it seems to help prevent specific diseases.

All the serious recent work I could find has utterly failed to confirm the once-fashionable claims that certain "stressful life-events" tend to precede the appearance or recurrence of clinical diseases apart from the psychiatric syndromes. For example, see J. Inf. Dis. 178S1:S67, 1998 (zoster), Arch. Int. Med. 159: 2430, 1999 (genital herpes), Cancer 77: 1089, 1996 and Cancer 79: 105, 1996 and Br. Med. J. 304: 1078, 1992 and Br. Med. J. 319: 1027,1999 (breast cancer); Arch. Gen. Psych. 49: 396, 1992 and Am. J. Psych. 148: 733, 1991 (AIDS); Am. J. Card. 68: 1171, 1991 (coronary disease); Ann. Int. Med. 114: 381, 1991 and Gut 31: 179, 1990 inflammatory bowel disease). The one exception is multiple sclerosis, where a relationship has long been clear (Br. Med. J. 327: 646, 2003). Also discredited is the old "holistic" claim that serious disease and death are more likely after bereavement and so forth (J. Behav. Med. 13: 263, 1990). By the mid-1990's serious researched had stopped even looking at this stuff.

You may hear that people unconsciously choose particular diseases to "symbolize their emotional conflicts". Patients are blamed for being sick because they have unhealthy attitudes. In some circles (both "liberal-holistic" and "conservative-spiritual"), people scapegoat the sick. This is cruel, and it is also groundless (NEJM 312: 1570, 1985).

Be aware of the ways in which lifestyle affects disease, and the effect of the disease and its treatment on the "whole patient" and his or her associates. But be realistic.

Your patient has other problems besides the disease. It may help if you know what these are, but there is seldom much you can do about them.

You may run into "religious conservatives" who contend that unusual sickness means unusual wickedness, and "if you were really sorry for your sin, you would walk out healed", etc. It's hard to argue with these folks, but I'm not aware of any reason to think this is true. And following Job, I prefer incomplete answers to the obviously-wrong answers of uncharitable ignorance. See also Luke, "If a tower falls on you and kills you, does that mean you were more wicked than the next person?" "No."

A school of pop psychology (popular with both left-wingers and right-wingers, it seems to have peaked in the late 1980's, but is still with us) emphasizes "everyone is an addict of some kind and is either in recovery or in denial", "you cannot begin to solve the problems of others until you have solved your own", and "the process of recovery is never finished". Only an ideologue would consider these to be better than half-truths.

No reasonable person would deny the importance of lifestyle in several common diseases, and the importance of attitude and participation in some situations faced by sick people. But be aware that many of your patients who have non-lifestyle-related diseases are being told they are "responsible", "have bad attitudes", etc., etc.

I note with some satisfaction an increasing use of the compound word "self-empowerment" by today's trendoids. As far as I can tell, it means, "Quit sobbing, shut up, wise up, act smart, and make a life for yourself." Watch for even more of this, especially in view of diminishing public's indulgence for (and tolerance of) do-nothings and crybabies.

Patients like to have the physician explain their diseases and procedures to them. They also like being given something to do to help in their treatment. They like to be treated courteously, and most of them like to be touched. If a physician does these things, patients will usually be satisfied with the overall care they have received.

Catch-phrases of the "political correctness" movement (which peaked in the early 1990's) include "different abilities / differently-abled" for handicaps, and "challenged" instead of "sick".

This led to some Alice-in-Wonderland litigation; for example, in some jurisdictions you cannot consider that being in a wheelchair is a worse outcome than being able to walk, because being in a wheelchair is "differently abled". I'd like to meet the left-wing nut, confined to a wheelchair because of a physician's error, who forgoes suing for damages, since he or she is now "differently abled".

Likewise, "challenges" are issued to winners, not to losers. (Even immunologic "challenges" are administered to creatures known to have fought off infection before.) I cannot regard simply getting sick, especially from some unhealthy and unwholesome practice, as making somebody a winner.

A word-search in 1993 showed these terms to be common in the allied-health literature, but non-existent in writings intended for physicians.

The Americans with Disabilities Act has made a level playing-field for companies wishing to hire the handicapped. It has also led to some bizarre law. There are some the-sky's-the-limit entitlements. And it only applies to disabled people. For example, if you have cystic fibrosis (a real disability) but can do a particular job, they cannot fire you for it, and have to make reasonable accommodations if you want to apply for the job. However, if you are fired by some moron for carrying the gene (this has happened), you have no legal recourse, and your rights have not been violated, because you are not disabled.

Today, "medical ethics" is a growth industry that pays extremely well (i.e., protection from lawsuits; Pediatrics 93: 310, 1994).

It was also obvious to this writer, when he was in training, that opposition by other physicians to discontinuing heroic therapy was motivated, at least in part, by economic incentives. (Yeah, there will never be a health-care reimbursement system without perverse incentives.) Remember this the next time somebody's "awful ethical dilemma" seems incredibly silly.

Today's ethicists talk about "futility" (JAMA 281: 937, 1999) as if it were a new scientific discovery, instead of just the plain truth that there are problems you can't solve despite massive effort and money. (Cynics: The "futility movement" coincided with changes in reimbursement plans for physicians and hospitals which meant that they would lose, rather than make, money when families insisted on "doing everything" for their dying loved one....) We even hear about something "beyond futility", i.e., disability and death with dignity (JAMA 287: 2253, 2002) and comfort.

FINAL NOTE

Pathology is the scientific knowledge that will enable you to find and treat disease effectively. Don't be discouraged! There's plenty you can do!-- ERF

Welcome to the introductory Pathology course. Most of you are undergraduate medical students. In this course you will learn the essential facts about human disease, so that you will be able to practice honest medicine.

Ideas about disease have changed during human history. People have thought about sickness as magical and mysterious, as abnormalities of whole persons, as abnormalities of individual organs, as abnormalities of cells, and as abnormalities of molecules.

Primitive people believe diseases are caused by gods and spirits. Diseases occur because people sin beyond the community standards, break taboos, or are bewitched. Primitive people treat diseases by praying, confessing their sins, and acting out magical ceremonies. In many cultures, the patient must show unquestioning faith, or the gods will be displeased and the patient will suffer. Most cultures also have some naturalistic ideas about disease. So primitive people also treat sick people by putting things into any and all body orifices, or even by creating new body orifices.

The ancient Egyptians made around 700,000,000 mummies. They took the organs out of the dead people and preserved them. Oddly, we have no record that Egyptian doctors ever examined their former patients' insides. They made some notes on practical therapeutics, but most of the surviving Egyptian medical literature is occult nonsense. One evil spirit is called "Mr. Pus-Friend, Cancer-Brother", etc.

The ancient Greek medical texts never mention supernatural causes of disease. The ancient Greeks had no concept of the real mechanics of disease, beyond observations of wounds, tumors, "swellings", etc. The best-known physician of ancient Greece was Dr. Hippocrates (460-377 BC). He and his students believed all diseases were processes that involved entire persons. Dr. Hippocrates sometimes tried to explain disease in terms of the traditional doctrine of four humors (blood, phlegm, yellow bile, black bile.) Disease is caused by imbalances of the four humors ("bad blendings," "dyscrasias") within the whole person. Disease was never localized to one part of the body. All this was wrong, but Dr. Hippocrates was no dogmatizer and the "four humors" myth probably did his patients no harm.

Hippocrates
NIH photo

Dr. Hippocrates was really an empiricist. He taught his students to carefully observe patients and watch what happened to them as they were treated. Dr. Hippocrates proved that sick people can be examined, their diseases classified, a diagnosis made for each, a prognosis established, and the patient treated intelligently. Although the Greeks understood almost nothing about real disease processes, they did discover what treatments helped for different patients. But except for minor surgery, they had no specific remedies for specific diseases. The Greeks cured almost nobody. Dr. Hippocrates is most famous for institutionalizing the high ideals of medical ethics. The Hippocratic oath made medicine a sacred calling rather than just a way of making a living. Hippocrates emphasized that some diseases are not treatable and that it is a credit to the physician to be candid about this. Two Alexandrian physicians did autopsies. Dr. Herophilus (335-280 BC) to do the first descriptions of cadaver dissection, and Dr. Eristratos (310-250) to correlate organ changes with diseases (ascites with cirrhosis, etc.) Their work had no real impact on the understanding of disease. They tried to correlate their findings with the clinical pictures with some success, but they had no influence on prevailing dogmas.

Dr. Cornelius Celsus (first century AD) described medical practice in his time in De Medicina. This book includes descriptions of heart disease and mental illness, and the four classic signs of inflammation.

Dr. Claudius Galen (130-200 AD), another Roman, began his career as the government physician to the gladiators. A careful observer, Dr. Galen soon became a famous physician, writer and lecturer. He discovered and explained several anatomic structures, including the recurrent laryngeal nerve, which he named "Galen's nerve." He wrote up some amazing experiments he did on living animals, and he published long lists of the rich and famous people who attended his lectures.

Galen
NIH photo

Dr. Galen dissected Barbary monkeys instead of humans. His mistakes included the five-lobed human liver, the two common bile ducts, and the holes where the blood goes through the septum of the heart. Dr. Galen's work remained the absolute authority until time of Dr. Vesalius. At anatomy demonstrations in the middle ages, the learned anatomy professor read out loud from Galen while the lowly morgue attendant cut on the body. If the morgue attendant found something that was not in "Galen", the professor ignored it. So there was exactly no progress in anatomy or anatomic pathology.

Dr. Celsus and Dr. Galen knew how inflammation and cancer looked and acted, and they emphasized patterns of symptoms and signs. For lack of any better theory of pathology, both these Roman doctors subscribed to the "four humors" idea of Dr. Hippocrates. Dr. Galen was also an amateur pagan philosopher and some of these writings survive too. He respected his Jewish and Christian neighbors, and was opposed to the persecutions. Like Dr. Hippocrates, Dr. Celsus and Dr. Galen had no concept of organ pathology, and they probably cured nobody.

Neither Dr. Hippocrates nor Dr. Galen ever did an autopsy (at least lawfully). Ancient and medieval superstition prohibited opening a dead body. Pathologic anatomy was limited to observing war wounds, bone injuries, skin diseases and a few clinical signs. In the middle ages, the Moslem world produced the best physicians. They were excellent observers of the living, but did not do autopsies. It took special permission from the pope to allow Dr. Mondino de Luzzi to perform an autopsy in front of an audience; this took place in Bologna in 1316. The autopsy (necropsy, post-mortem exam, "post") became popular only after Dr. Vesalius's anatomic work (1543). People realized that they could learn about the world by observing it, instead of reading old books.

When autopsies became legal, early investigators made many discoveries that offered new understandings of old diseases, but nobody understood essential diseases processes. As Dr. Galen and humoralism lost popularity, new fad theories emerged to explain all disease. In countries where it was legal to teach the existence of atoms, methodist physicians attributed all disease to changes in distances between atoms. In countries where atomic theory was still banned for ideological reasons (too unspiritual), pneumatist (vitalist) physicians blamed disease on the spiritual forces that controlled physiologic processes.

All previous anatomic pathology was superseded in 1761 by Dr. John Morgagni, an Italian. He called his charming series of 700 autopsies The Seats and Causes of Disease, Investigated by Anatomy. Written at age 78, it summed up a lifetime's experience and is still a great read. On the evidence, Dr. Morgagni was a genuinely good human being and was among the most beloved people of his era. Thanks to his work, all disease was now recognized as disease of organs, and disease "sat" in different organs in different patients. Dr. Morgagni meticulously related his patients' symptoms to their diseased organs, making the first clinico-pathologic correlations. This was real progress, but Dr. Morgagni had no real idea of how disease in one organ caused malfunction in another organ, or even what disease is. Since every major organ has one vein, Dr. Morgagni's students developed the next fad theory. All disease was due to phlebitis, inflammation of the vein draining the organ.

Morgagni
NIH photo

Dr. Karl Rokitansky of Vienna was the next great autopsy pathologist. He wrote the Handbook of General Pathologic Anatomy (1846), and in his day was the world's most famous pathologist. Vienna law decreed that everybody who died got autopsied by him. He did over 30,000 autopsies personally. Dr. Rokitansky was a colleague of Dr. Joseph Skoda, the world's most famous clinical diagnostician. In the morning, Dr. Skoda taught all the Viennese medical students on the wards and tried to make diagnoses on the patients who were still alive. In the afternoon, everybody went downstairs to see Dr. Rokitansky's autopsies on the dead patients and find out whether Dr. Skoda had been right. Thus, Dr. Rokitansky performed the most important function of the medical pathologist, relating clinical signs and symptoms to pathologic anatomy, and correlating function and structure. The medical students handled all the fresh organs without gloves and then go deliver babies without washing their hands. This was unhealthy, but it continued until a young instructor named Dr. Ignatius Semmelweiss introduced mandatory hand-washing. But that's another story.

Semmelweiss
NIH photo

Dr. Rokitansky and Dr. Skoda agreed that the medical therapeutics of their era had little to offer. (They were right.) Dr. Skoda's motto was "Forget treatment, the diagnosis is everything". They called this approach therapeutic nihilism. Dr. Skoda the clinician and Dr. Rokitansky the pathologist were brilliant, but nobody really had any idea what caused most disease. They didn't even know about germs. Dr. Rokitansky came up with a theory to explain all disease as crasias and dyscrasias. These caused the non-cellular ground substance to produce new defective cells.

Rokitansky NIH photo

Rokitansky NIH photo

Skoda
NIH photo

Dr. Rudolf Virchow (1821-1902) is the greatest pathologist of all time. Dr. Virchow was a German, a tiny man, almost a dwarf. Dr. Virchow started as a junior autopsy pathologist working for the German government at the University of Berlin. He liked to cut thin sections of diseased tissues with a razor, and look at them using the latest technology, the microscope. Dr. Virchow first achieved renown by discovering leukemia and myelin.

During the German revolution of 1848, there was a bad typhus epidemic. The government sent Dr. Virchow to find out what caused typhus. After investigating, he announced that typhus was caused by the conservative politicians, who had done nothing about poverty and overcrowding. The government fired him for saying this, and he continued his work elsewhere. Since Dr. Virchow's time, pathologists have remained interested in the social pathology that produces disease.

Dr. Virchow's book Cell Pathology (1858) is the basis for all modern pathology. Dr. Virchow worked out hypertrophy, hyperplasia, metaplasia, basic acute and chronic inflammation, granulomas, thrombosis, infarction, the nature of tumor growth and routes of tumor spread, and much more. If nobody tells you who discovered something, there is a good chance it was Dr. Virchow. Dr. Virchow established the principle that all cells come from pre-existing cells and he emphasized that all disease is disease of cells. Dr. Virchow's ideas were introduced within months of the two other great unifying principles of today's science, the periodic table of the elements and the common origin of living things. Although he described much of the anatomy of illness, and was not himself an experimentalist, Dr. Virchow realized the overriding importance of the new science of experimental physiology. He emphasized that morbid anatomy always reflects disordered pathophysiology.

Dr. Virchow became a member of the German senate, for his time an extreme liberal, even a pinko. Dr. Virchow liked to describe the body as a republic with every cell equal. Especially, Virchow despised notions of "race" as unscientific (Nature 427: 487, 2004). Chancellor Otto von Bismark hated Dr. Virchow so much that in 1865 he challenged him to a duel. Dr. Virchow accepted, and chose as the weapons two sausages. He stipulated that his sausage was to be a clean cooked sausage, and Bismark's sausage was to be loaded with trichinosis larvae, served raw, and eaten by Bismark.

Dr. Virchow became the world medical dictator and the arbiter of scientific controversy. He was usually right, but was skeptical about micro-organisms as causes of diseases. When Dr. Pasteur first demonstrated the streptococcus bacteria that cause human infections, Dr. Virchow was in the audience. Everybody looked to see what old Dr. Virchow would say about the new claim. Dr. Virchow nodded and walked out without saying anything, and Dr. Pasteur and his germs became official.

Virchow NIH photo

Virchow NIH photo

Virchow NIH photo

Virchow NIH photo

Virchow Humor

Virchow NIH photo

Dr. Louis Pasteur (late 1800's) was the first person to conquer diseases using the methods of laboratory science. He first solved the mystery of bad-tasting wine, then explained and prevented epidemic disease among silkworms, anthrax in sheep, and finally rabies in humans. Dr. Pasteur was a chemist and could not stand the sight of blood. He considered going to medical school but never went because he was terrified of having to watch an autopsy.

Pasteur NIH photo

Cohnheim NIH photo

Dr. Virchow's student Dr. Julius Cohnheim worked out much of the pathology of acute inflammation and of tuberculosis. Dr. Cohnheim's pupil, the flamboyant Dr. Paul Ehrlich, devised many of the stains still in use by pathologists.

Ehrlich
NIH photo

In the mid-twentieth century, pathologists really started thinking about diseases of molecules -- the molecular basis of disease. Progress in biochemistry unravelled the defects in inborn errors of metabolism. Dr. Linus Pauling (1949) worked out the physical chemistry of red cell sickling in sickle cell anemia. Every effective therapy today is the result of the laboratory study of disease.

Pauling
NIH photo

Today there is a new emphasis on disease as it involves whole persons. Today's most important diseases are lifestyle-related. Everyone recognizes the importance of habits in acquiring lung cancer, emphysema, heart disease, cirrhosis, and AIDS. Emotional factors influence other diseases, including high blood pressure, asthma, skin diseases, gastrointestinal diseases, and perhaps even cancer. Physicians are alert now to the ways in which illness affects a person's whole life, to the emotional needs of patients that cause them to seek medical attention, and to their spiritual needs, patient dignity, and their rights to make decisions about their own health care.

* In the twentieth century, two pathologists have distinguished themselves as spokespersons for human conscience, though you might not agree with one or both. Pathologist-turned-politician Salvador Allende took steps to turn Chile into his dream of a Marxist state. (Your lecturer considers this a misguided ideal.) Canadian John McCrae wrote the brilliant World War I lyric, In Flanders Fields. (Read it. Is it a militaristic poem, an anti-war poem, or both?)

In Medical Pathology, you will think about all these things at once. Pathology deals with abnormal gross and microscopic anatomy, abnormal biochemistry, and abnormal physiology. Disease involves molecules, cells, organs, whole persons, and groups of people. We are sensitive to all aspects of disease. We'll put everything together in this course.

-- Ed Friedlander, M.D.