Perspectives on Disease

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 400,000 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)
• Diarrhea (kills >10,000 babies daily)
• Diphtheria
• Neonatal tetanus (still a terrible problem; 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 . 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. Around 40% of hospital autopsies show a previously-unknown illness contributing to death (Arch. Path. Lab. Med. 123: 191, 1999). 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                                                                                                                                                                                        
•  Conduction system problems 
• Cocaine use
• Electrolyte problems (i.e., diuretic abuse)
• Myocarditis

The average American's chances of being killed by 

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.
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 moredeaths 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.
 
The commonest chromosomal syndromes are Klinefelter's (XXY; 1/850) and Down's syndromes (trisomy 21; maybe 1/1000). Turner's (XO) and "supermale" ( 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):

• African tick-bite fever
• Alexithymia
• Angioimmunoblastic lymphadenopathy
• Anticardiolipin antibody ("lupus anticoagulant") disease
• Asperger's (high-functioning autism, great at science and math, much difficulty learning scial 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
• Eosinophilic esophagitis
• Esophageal chest pain 
• 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.)
• Inflammatory aortic aneurysm
• 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
• Obliterative bronchiolitis (a major factor in tobacco-related lung disease)
• 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
• Serrated adenoma of the colon, and its premalignant potential
• Sjogren's involvement of the nervous system
• 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)