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A biopsy is tissue removed from a person during life and that will be sent to the pathologist for diagnosis. A rotten tooth or an ingrown toenail will not be sent for diagnosis; most other tissues, including resections where the diagnosis is already made, will be sent and hence are biopsies. • Closed biopsy means the pathologist or clinicians put a needle into the mass to obtain a few cells ("needle aspiration" or "aspiration biopsy") or a bit of tissue ("needle biopsy" or "core biopsy"). Open biopsy means an incision was made to obtain a larger mass of tissue. • Excisional biopsy means the mass or entire organ was removed for diagnosis and perhaps cure as well. • Autopsy ("necropsy") is the opposite of "biopsy". The pathologist examines part or all of a dead body.
Symptoms are, of course, the patient's subjective observations, while signs are evidence of disease discovered by the physician. Unless otherwise qualified, "signs" are abnormalities on physical exam, and findings are physical, lab or x-ray results. Lesions are fundamental pathologic changes (usually anatomic derangements, though they may be molecular) that the pathologist can exhibit. • A syndrome is a cluster of related symptoms and/or signs not necessarily due to the same causes in different patients, but typically due to a single cause in any individual patient. Your understanding of basic anatomy, biochemistry, and physiology can help you understand the various syndromes. A diathesis is a condition that interferes with normal response to minor hazards of daily living. (The usual use of this odd word is "bleeding diathesis", i.e., the patients are fine until they need to clot their blood.)
you could consider the "cause of fatal measles in poor countries" to be the measles virus. bad nutrition. it is not always clear how a particular mutation leads to a particular disease. the malnutrition that makes the infection more severe.bugs. • Intrinsic etiology means the genetic component of any disease. poisons. Although the human genome is now sequenced. and "Big Robbins" begins with an important point: it is simplistic to think of an individual disease having a single "cause". For example. or the local laws that forbid immunization. the poverty and crowding in which the infection flourishes.• The etiology of a disease is its "cause". • Extrinsic etiology is everything else -. lots more . physical injury.
" "Finding a Reinke crystalloid in a primary benign testicular tumor is pathognomonic of Leydig cell adenoma. cellular. ultrastructural. The story -. • By convention. and molecular levels.") . ("Hearing the fetal heart tone is pathognomonic of pregnancy.from etiology to symptoms and signs -. by which the disease develops. • Pathognomonic is a big word that means that a particular abnormality is found only in one condition. a pathogen is a micro-organism that causes disease.is always complicated. • Morphology / morphologic changes / morphologic derangements is whatever the pathologist can exhibit grossly or under the microscope.• The pathogenesis of a disease is the sequence of events at the organ.
"cases per 100.000 people per year"). The prevalence of a disease tells how many people are affected at any one time (typically. prevalence equals incidence times average duration. . i. • The incidence of a disease is the number of new cases per unit time (usually given as "new cases per 100.• Organic disease has a clear anatomic and/or chemical lesion.000 people"). • The risk of a disease is how much your unusual situation (typically some kind of exposure to an uncommon hazard) increases your chance of getting the disease compared with everybody else.. while functional disease has not (yet?) yielded its deep secrets and is assumed to result from subtle nervous system abnormalities and/or mild mechanical problems. Obviously. Pathologists seldom talk about "the functional diseases". don't expect us to talk about migraine or low back pain with the same zeal as we discuss sickle cell anemia.e.
The prognosis of a disease is the expected outcome for a particular case. The prognosis is likely to be influenced by the diagnosis. and the available treatments. once it is identified. the age and general health of the patient. "poor prognosis" suggests permanent disability or death. . "Good prognosis" suggests that recovery is likely.• The diagnosis is the name given to the particular disease.
under some circumstances.) Right or wrong.S. . of the U. if not all. Most states now have a Natural Death Act.• Disease can ruin the quality of life for a person. (Of course. • Managed care saved the health care system in the mid-1990's. active euthanasia. you don't stop treating all patients who say they want to die. reflecting a world-wide movement. by the time you are in practice. Managed death is next. will almost certainly be legal throughout most. Most of us physicians find it hard not to treat disease under any circumstances.
• Hematoxylin (blue-purple) is a metal chelator. (* Eosin. water.) • Air. which is fluorescent. calcium salts. eosin is acidic and stains bases") isn't exactly so.• • Hematoxylin and eosin (H&E) is the standard tissue stain. We usually use it with aluminum ions. which link it to fixed phosphate groups. . The pedagogical explanation ("hematoxylin is basic and stains acids. and carbohydrate end up unstained. Hematoxylin stains nucleic acids. is a major component of many colors of lipstick. It's also the red dye on pistachio nuts.) • Eosin (red) binds to free amino groups and thus stains arginine and lysine pink. and bacteria blue-purple. fat. (* Hematoxylin comes from an exotic jungle tree.
.. insoluble sugar compounds such as .. i. • Anything with a cis-dihydroxy group. . – glycogen.• Periodic acid-Schiff (PAS) is a stain based on the familiar * periodic acid (H+IO4-) oxidation (cis-diols to aldehydes) and * Schiff-base reactions.e.
• Prussian Blue uses a special solution of * ferrocyanide. • Beta-pleated proteins in humans are abnormal and are called amyloids . • By the familiar reaction (college • cCongo Red is a special dye that fits tightly into beta-pleated proteins of all sorts.
This shows up mycobacteria (TB bugs) and certain other rare substances . others) stain certain waxes a permanent red (or some other color).• Sudan / Oil Red O are oil-based stains that can only be used on thin slices ("frozen sections") of tissue from which fat has not been removed. auramine O. • These stain only fat (usually black or bright red • Acid-fast stains (ZN.
• Acid-fast stains (ZN. auramine O. This shows up mycobacteria (TB bugs) and certain other rare substances . others) stain certain waxes a permanent red (or some other color).
but soon fat globules occur that are not membrane-bound. Failure of lipoprotein secretion by the liver. There are at least six mechanisms by which the liver cell accumulates fat during disease. Fatty change of injured cells occurs classically in the . Impaired fatty acid oxidation by the liver 4. any or all of which may be operating in a given situation. Excess esterification of fatty acid to triglycerides by the liver 5. "steatosis"): accumulation of excess neutral fat in vacuoles within non-adipocytes If there's one big fat vacuole.FATTY CHANGE • • • • • • • • • • • ("fatty metamorphosis". If there's many little fat vacuoles. liver and the heart . 1. Too little apoprotein synthesis by the liver 6. it's "microvesicular". Too much free fat coming to the liver 2. "fatty degeneration". it's "macrovesicular". Too much fatty acid synthesis by the liver 3. At first the fat accumulates in the rough endoplasmic reticulum.
* outdated tetracycline. * non-alcoholic steatohepatitis. Reye's syndrome. and all six mechanisms are known to contribute here. • If the fat is periportal.• Fatty liver develops during heavy drinking. pregnancy (rare and mysterious). * the bad kind of galactosemia. carbon tetrachloride. and * following ileal bypass for weight reduction. • Other causes of heavy-duty fatty liver include kwashiorkor (why?). think of malnutrition / total parenteral nutrition / AIDS wasting . poisoning by phosphorus.
the fat is probably harmless enough.• After a boozy weekend. • Patients with fatty livers do occasionally "die of it". • By itself. but to the sick liver's not being able to buffer a falling blood glucose. A blow to a drinker's abdomen can disrupt enough hepatocytes to cause fatal fat embolization (lung. a person can have several hundred grams of excess fat in the liver. People dying on benders often have livers weighing more than 4000 gm (normal is 1500 gm or so). brain). and sections float. Or the patient may die of hypoglycemia (not due to the fat. can be palpated below the costal arch.) . but its presence is a marker for injury. These livers hurt (stretched Glisson's capsule).
Here is fatty metamorphosis (fatty change) of the liver in which deranged lipoprotein transport from injury (most often alcoholism) leads to accumulation of lipid in the cytoplasm of hepatocytes. .Fatty liver • Intracellular accumulations of a variety of materials can occur in response to cellular injury.
and produces a "tiger-stripe" or "thrush-breast" heart.. • (2) The heart damaged by diphtheria exotoxin is uniformly flabby and often fatty. fat-laden cell may not be permanently damaged or killed. both fortunately rare today: • (1) It most often reflects poor oxygenation (i. .Fatty change in the heart • is seen in two classic situations.e.). And remember cells can and do die without undergoing fatty changes. • Notice that the injured. chronic severe anemia). (The old idea that diphtheria toxin block fatty acid burning by inhibiting the carnitine shuttle has been replaced by the finding that the protein is a nonspecific and very potent inhibitor of protein synthesis. It is distributed away from the vessels.
some texts suggest that only dead things calcify. and X. Of course.. that's the end of the cell. in the presence of normal overall calcium-phosphorus metabolism. IX. Regardless of cause. . the media of large arteries ("Monckeberg's") and the mitral valve annulus.) In intracellular calcification. (* If there is any doubt.) This is calcification that takes place locally. Calcium salts (hydroxides. phosphate-hydroxides) are deposited. VII. This includes the pineal gland. calcium salts stain dark blue on H&E. not just radiologists. calcium salt is complexed to coagulation factors II. This is simply not true. special stains like the Von Kossa of Alizarin red demonstrate it is calcium. the ones that contain gamma-carboxy glutamic acid (and therefore require vitamin K. * In extracellular calcification. causing deadly aortic valve stenosis. "Dystrophic" means "seeking out the bad". Several normal structures tend to calcify during adult life. While a necrotic cell whose mitochondria calcified may provide a nidus for stone-building. etc. the first organelle to calcify is usually the mitochondrion..CALCIFICATION: • • • Dystrophic calcification • • • • • • • • A subject of interest to most physicians. the cartilages in the airways. These are probably harmless. Around 1% of adults develop calcifications in their otherwise-normal sinuses of Valsalva. The calcifications may be of any size..
1998. PNAS 95: 7896 & 8274. One suspect is certain nanobacteria that thrive on the hydroxyapatite surfaces that they build. Tetracycline-sensitive -let's wait and see. . and they are told that this is "proof that the circulation was being restored. Patients feel their fingers tingle during the infusion. • * "Chelation therapy" (infusions of EDTA) is a perennial health fraud that claims to "cure atherosclerosis by removing calcium from the walls of vessels"." Explain.• * Nobody knows why most dystrophic calcifications happen.
Certain tumors contain "psammoma bodies". histoplasmosis. (Think of thyroid cancer. others) often calcify. somatostatinoma). ovarian cancer. Scars (surgical. myocardial) often calcify. especially congenitally bicuspid aortic valves (another common cause of aortic valve stenosis). Caseous granulomas (tuberculosis. The reasons are generally obscure. The fingertip pulp calcifies in scleroderma and CREST syndrome. meningioma. Malformed or damaged cardiac valves tend to calcify. Little spherical calcifications inside giant cells in granulomas are called "Schaumann bodies" .• • • • • • Dystrophic calcification is characteristic of other diseases as well. little spherules of basement membrane that calcify.
) • * Calcification of the pinna of the ear occurs for some reason in some cases of longstanding adrenocortical insufficiency (Addison's disease. If the celiac plexus is involved. Path.• * Uterine fibroids (smooth muscle tumors) often calcify. it may be retained for years as a "lithopedion" ("stone child" -. . this produces one of medicine's most intractable pain syndromes. 1983. 107: 91. (This is an ancient finding: Arch. there are other causes too). "Within the Walls of Tyre"). • A special case of dystrophic calcification is precipitation of calcium stearate in pancreatitis-associated fat necrosis. • If a fetus dies and calcifies.* read Michael Bishop's famous non-supernatural horror story.
Metastatic calcification: • • • • • • • "Metastatic" means "another place". and the walls of small blood vessels. Note that all but the last are sites of pH gradients. the gastric fundic epithelium (near parietal cells). 2004. the basement membranes of certain renal tubules. * High blood calcium is usually due to cancer destroying bone. * The most grisly example of metastatic calcification is the severe autosomal recessive disease familial tumoral calcinosis. 36: 579. Here the serum calcium and/or phosphate ion concentration is already elevated for some reason. * Virchow first explained the mechanism. Genet. relating metastatic calcification of lung and stomach to demineralization of the bones and kidney failure. high hPTH levels (parathyroid adenomas and hyperplasias. . rarely others). Metastatic calcification occurs predictably in the alveolar walls. squamous cell carcinoma of the lung. Gene GALNT3: Nat. milk and antacid abuse. High blood phosphate is almost always due to kidney failure or massive tumor lysis. vitamin D abuse. sarcoid. Healthy tissues calcify. The calcium precipitates first where there is excess hydroxyl ions.
respiratory insufficiency (* "pumice lung") or renal tubular failure can occur.• In very severe lung or kidney involvement. But usually metastatic calcification is harmless evidence of serious disease elsewhere. .
Calcium is more likely to be deposited in tissues that are damaged. At the far left is an artery with calcification in its wall. There are also irregular bluish-purple deposits of calcium in the submucosa. .• This is dystrophic calcification in the wall of the stomach.
• Here is so-called "metastatic calcification" in the lung of a patient with a very high serum calcium level (hypercalcemia). .
bowel ischemia. ruptured aortic aneurysms. Some atherosclerosis is inevitable. strokes.Atherosclerosis • : an accumulation of cholesterol and debris in cells of the intimal layer of the large arteries. angina pectoris. leg claudication. kidney destruction (by "atheroembolization") and gangrene of the legs. • Severe atherosclerosis causes transient ischemic attacks. eventually ruining the artery. heart attacks. .
kid. It is inert though ugly. where it remains indefinitely. ("If you keep smoking.Carbon • Carbon particles enter our bodies in smoke and soot or as the pigment in jailhouse tattoosCarbon settles in macrophages. Carbon in the lungs and nearby lymph nodes is called "anthracosis". your lungs will get blacker and blacker!") .
"peroxidated". "fuscus" is Latin for brown) • This is another brown pigment that is now known to be the un-digestible residue of subcellular membranes whose unsaturated lipids have been scrambled ("polymerized".Lipofuscin • (* "lipochrome". etc. .) by free radicals.
It is of no major consequence.• The yellow-brown granular pigment seen in the hepatocytes here is lipochrome (lipofuscin) which accumulates over time in cells (particularly liver and heart) as a result of "wear and tear" with aging. but illustrates the end result of the process of autophagocytosis in which intracellular debris is sequestered and turned into these residual bodies of lipochrome within the cell cytoplasm .
which forms a striking blue complex with stainable ferric ion ("Prussian blue . a complex mixture of proteins and ferric ions. It is faintly visible as shiny golden granules in unstained tissue sections. • • The best way to demonstrate hemosiderin is using acid ferrocyanide.Hemosiderin • The stainable form of iron is hemosiderin.
• A Prussian blue reaction is seen in this iron stain of the liver to demonstrate large amounts of hemosiderin that are present within the cytoplasm of the hepatocytes and Kupffer cells. only a small amount of hemosiderin would be present in the fixed macrophage-like cells in liver. . Ordinarily. as part of iron recycling. the Kupffer cells.
yellow-orange pigment that results from breakdown of porphyrin rings (mostly hemoglobin). Nasty alleles are Crigler-Najjar.BILIRUBIN JAUNDICE • This is the non-iron-containing. a must-know for today's clinicians. . • Bilirubin by itself is insoluble in water and is carried on albumin to the liver. where hepatocytes conjugate it with glucuronic acid and pour it into the bile. Most common is Gilbert's non-disease (francophiles say zheeel-BAYRRRR's). • Elevated levels of bilirubin in the blood mean jaundice. why?) • Liver cells can't conjugate bilirubin fast enough: – most diseases of liver cells – just being a newborn ("physiologic jaundice of the newborn") – hereditary defects. pathologists look for bilirubin gallstones and elevated urinary urobilinogen. Mechanisms: • Too many red cells being broken down: – all the hemolytic processes (from jogging to sickle cell disease to the intramedullary lysis of normoblasts in thalassemia minor and pernicious anemia.
• The sclera of the eye is yellow because the patient has jaundice. The normally white sclerae of the eyes is a good place on physical examination to look for icterus . or icterus.
and he continued his work elsewhere. Since Dr. Dr. Virchow. Virchow established the principle that all cells come from pre-existing cells and he emphasized that all disease is disease of cells . The government fired him for saying this. The government sent Dr. Dr. Virchow's book Cell Pathology (1858) is the basis for all modern pathology. If nobody tells you who discovered something. Virchow to find out what caused typhus. Dr. there is a good chance it was Dr.• Dr. basic acute and chronic inflammation. the nature of tumor growth and routes of tumor spread. Virchow first achieved renown by discovering leukemia and myelin. there was a bad typhus epidemic. He liked to cut thin sections of diseased tissues with a razor. After investigating. Rudolf Virchow (1821-1902) is the greatest pathologist of all time. granulomas. the microscope. hyperplasia. and much more. and look at them using the latest technology. he announced that typhus was caused by the conservative politicians. Virchow started as a junior autopsy pathologist working for the German government at the University of Berlin. Dr. who had done nothing about poverty and overcrowding. pathologists have remained interested in the social pathology that produces disease. Virchow's time. • • Dr. infarction. Virchow was a German. almost a dwarf. • During the German revolution of 1848. Virchow worked out hypertrophy. Dr. metaplasia. thrombosis. a tiny man.