Supplemental reading
Traditionally the light
microscopic morphologic changes indicative of nonlethal injury to cells are
called degenerations. It is important to understand that the term degeneration
always implies reversible injury. The morphologic expressions of cell injury
visible with the light microscope involve principally the cytoplasm. The
nucleus is remarkably unaffected, save, perhaps, for some clumping of the
chromatin against the nuclear membrane. three distinctive patterns of degeneration
can be recognized: cellular swelling, hydropic degeneration and fatty change.
There is some virtue in differentiating among these three patterns because they
offer clues to the nature of the injury. For example, fatty change in the liver
is characteristic of alcoholism but is rare in viral hepatitis. Conversely, the
acute stages of viral hepatitis typically are marked by striking hydropic
degeneration (ballooning) of liver cells. However, it must not be assumed that
individual agents always induce specific morphologic alterations; at best the
correlations are imperfect. Sometime an injurious influence first induces
cellular swelling, followed by hydropic degeneration, in turn leading to fatty
change. Such a sequence is not invariable, however. sometimes cellular swelling
passes directly to fatty change or, alternatively, the manifestations of cell
injury may not progress further.
Fatty change is the most ominous
of the cellular degenerations and commonly encountered in the liver, heart and
kidneys. Although reversible, it often implies severe injury and may even
forebode cell death. It is characterized microscopical by the accumulation of
fat vacuoles within parenchymal cells. Early there are numerours small vacuoles
dispersed throughout the cytoplasm, creating a foamy appearance under the light
microscope, but nucleus is not displaced. More intense lipid accumulation leads
to coalescence of these small droplets into one or more very large vacuoles,
which frequently distend the cell and displace the nucleus, sometimes
compressing it against the plasma membrane. Indeed, in very advanced fatty
change, the cell may appear to be transformed to a fat storage cell. Sufficient
accumulation may distend the cell until it ruptures the plasma membrane and coalesces
with adjacent cell into a so-called fatty cyst. Whatever the size of the
vacuoles, with routine tissue stains(e. g. , hematoxylin and eosin) they appear
as cleared spaces. Standard histologic techniques employ lipid solvents which
remove the vacuolar contents. However, with appropriate aqueous fixatives and
frozen section techniques, the
lipid content can be preserved and stained with Sudan Ⅳ or
Oil Red O, imparting a red –orange coloration to the lipid globules.
Congestion, or hyperemia, is the presence in the vessels of a tissue or organ of more than the normal amount of blood. Congestion is of two types, active (arterial) and passive(venous), and it may be acute(of short duration) or chronic (long-standing).
Passive congestion is due to an
impairment of venous drainage. It may be more or less generalized as in
congestive heart failure, in which the entire pulmonary or systemic
circulation, or both, may be involved. Localized passive congestion may result
from venous occlusion by thrombi or ligatures or from venous compression by
adjacent diseased organs. The passive congestion that follows obstruction of
one or only a few veins is often transient because of the generally abundant
collateral circulation in the venous system. In such cases large collateral
veins often develop from previously insignificant vessels. In an organ involved
by passive hyperemia, the volume of blood is increased, but the rate of blood
flow is decreased.
In chronic passive congestion,
the persistent decrease of blood flow leads to ischemic (not pressure) atrophy
of the more sensitive parenchymal cells, while the stromal cells tend to
proliferate. Repeated capillary hemorrhages produce hemosiderin deposits. The
eventual microscopic picture is characterized by widely dilated capillaries
packed with red cells; atrophy, degeneration, and even disappearance of some of
the parenchymal cells; fibrosis; and deposits of hemosiderin in macrophages and
free in the tissues. Edema is a frequently associated lesion. The organs most
frequently involved by chronic passive congestion are the lungs, liver, spleen,
and pancreas.
The lungs in chronic passive congestion
are large, heavy, and frequently edematous. The cut section oozes blood freely
and has a rubbery firmness and a rusty brown color (brown induration of the
lung). In very severe cases the lung bases may be firm, gray, and relatively
bloodless because of severe fibrosis. The large pulmonary arteries are
sclerotic with lipid or fibrous intimal plaques. The microscopic changes
include markedly dilated septal capillaries which bulge into the alveolar,
edema and fibrosis of the alveoli septa with eventual loss of capillaries,
cuboidal alveolar lining cells, and many hemosiderin-laden macrophages in the
alveoli. The small pulmonary vessels may show fibrous or muscular thickening of
their walls.
The liver in chronic passive congestion is initially enlarged but eventually becomes smaller than normal. The external and especially the cut surfaces have a mottled appearance with a continuous purple background (central areas) in which are spaced round or branching, slightly bulging tracts of yellowish tan tissue averaging 1 mm in size (portal areas). This yellow and purple mottling is similar to the cut surface of a nutmeg seed—hence, “ nutmeg liver”. Microscopically the sinusoids are markedly dilated, especially centrally where the liver cells are atrophic (ischemic atrophy due to sluggish blood flow) and may show fatty degeneration, while the periportal cells are normal. In severe cases necrosis of central liver cells occurs and leads to extravasation of red blood cells into the spaces previously occupied by the liver cells—hemorrhagic central necrosis.
Definition and Nature of Inflammation
When living tissue are
injured, a series of changes, which may last for hours, days or weeks, occurs
in and around the area of injury.
This response to injury is known as inflammation, the term being derived
from the Latin inflamare meaning to burn.
The injury is abnormal, but
the body's reaction, inflammation, is a normal, if complex, physiological
reaction, the only one possible in the circumstances of that particular injury.
Its purpose is to localize and eliminate the causative agent, to limit tissue
injury and then to restore the tissue to normality or as close to normality as
possible. This reactive nature of inflammation was first recognized by John Hunt
(1794), who, after his studies of war wounds, concluded: ‘Inflammation is itself
not to be considered as a disease, but as a salutary operation consequent
either to some violence or some disease.’
Many different types of
injury may evoke inflammation. They may be physical agents, chemical substances,
hypersensitivity reaction, microbial infections, and necrosis of tissue and so
on. The reaction in the first few hours after injury is stereotyped and widely
different kinds of injury cause a similar initial response-the acute
inflammatory reaction. The terms acute and chronic refer to the duration of the
response. Acute inflammation lasts for days or a few weeks; chronic inflammation
persists for weeks, months or even years.
The inflammatory response is usually beneficial, indeed it
is essential in combating most infections and in limiting the harmful effects
of many toxic agents. However it
is not always of benefit. There are many situations when destruction of tissue
or other untoward effects are due not to the damaging agent but to one or other
aspect of the body's response to injury. For example in acute inflammation of
the larynx, there may be sufficient inflammatory swelling to obstruct the
airway and cause death from asphyxia. Inflammation is best considered not as a
single process but as a collection of distinct processes, each of which may
have evolved for defense against injury, but each of which has also potentially
deleterious effects.
The Mechanism of Cancer Metastasis
Metastasis is the spread of
cancer from a primary tumor to distant sites of the body and is a defining
feature of cancer. Three steps, as follows, are necessary for production of
metastasis: (1) Invasion of cancer cells into lymphatic or blood vessels or
into appropriate tissue spaces. (2) Detachment of the cells with embolization
or other mechanical transport, and (3) lodgment and progressive growth of the
cells in a new location. Every cancer has its own particular growth
characteristics, including the ability to invade and metastasize, the time
required for metastasis, and the place to which metastases occur. Metastatic
ability of a tumor is, of course, influenced by its location, since the nature
of the vascular supply of the primary site is important. Many cancers cell seem
to be capable of entering the first step in the development of metastasis without
necessarily continuing the process to the point of completion. For example, blood
vessel invasion is relatively common in many cancers, but it does not
necessarily mean that metastasis has already taken place, or that it will.
Transport, the second step in the development of metastasis, is more or less
mechanical. It is assisted by natural movements of the part, such as
peristalsis and by excessive manipulation of the tumor by the patient or
physician. Again, however even the presence of tumor cells in the blood stream
does not necessarily mean that metastasis will take place. There is
considerable evidence that tumor cells are often embolic in blood or lymphatic
vessels without production of metastasis. Many tumor cells must be lost along
the course.
It is evident
that the third step in the development of metastasis is of much importance,
tumor cells must lodge and grow in their new location. Not all organs and
tissues are equally susceptible to the development of metastases. For example, metastases
are relatively uncommon in the spleen or in skeletal muscle, although both must
receive many tumor emboli. Conversely, metastases grow well in the liver. Such
difference in the "soil" are not well understood and may be related
to such factors as variation in vascular size and permeability, local
nourishment and local resistance.
Arteriosclerosis
Arteriosclerosis is a hardening and thickening of the walls of arteries. It is a generic term which includes several somewhat different lesions. The most common type of arteriosclerosis, termed arteriosclerosis without qualification, or atherosclerosis to emphasize the fatty plaques (atheromas), is characterized by anatomic changes mainly in the intima. Special types of arteriosclerosis are given qualifying names. Because of the increasing average age of the populace and the decreasing incidence of most infectious diseases, arteriosclerosis, through its effects on various organs, especially the heart and brain, has now become the most important single cause of death in the United States.
Arteriosclerosis is usually a
generalized change, but its severity may vary in different regions of the body.
The larger vessels are involved mainly, and changes are most readily seen in
the aorta. The arteriosclerotic aorta is dilated and often somewhat elongated
and tortuous. Scattered irregularly over the intima are elevated, pearly gray,
hard plaques with round or irregular outlines. Yellow halos surround some of
the plaques. Section of a plaque reveals a superficial layer of hyaline
connective tissue and a soft, yellow or orange, grumous or mushy center. In
severe cases the large plaques are ulcerated and partly covered by flat mural
thrombi. Other plaques may be calcified as thin, curved, scaly plates. Between
the plaques the intima is diffusely thickened, gray, and opaque and is
frequently longitudinally wrinkled because of post-mortem retraction (not
pitted as in syphilitic aortitis). The aorta as a whole is rigid and inelastic.
These changes are most severe in the lower abdominal aorta and in the iliac
arteries. Plaques tend to localize particularly about the openings of branches,
and there is usually an especially severe plaque at the site of insertion of
the ligamentum arteriosum.
In general, the muscular arteries undergo the changes of
arteriosclerosis later in life than does the aorta, and the resultant plaques
are more fibrous and less lipidized. An exception to this generalization is the
coronary arteries, which sometimes undergo arteriosclerosis rather early in
life, especially in men. Cases of coronary arteriosclerosis without significant
arteriosclerosis of the aorta or other vessels are not infrequent in men
between ages 30 and 50. Coronary plaques are mainly fatty in type and occur
predominantly in the proximal parts of the arteries. Cerebral arteriosclerosis
occurs late in life, and the basilar and middle cerebral arteries are most
severely involved. Arteriosclerosis often affects the internal carotid
arteries, especially near the bifurcation of the common carotids and within the
skull. Abdominal arteries, with the exception of the splenic artery, are rarely
the seat of severe arteriosclerosis, except at their origins from the aorta,
until quite late in life. Peripheral arteries, chiefly those of the lower
extremities, are often sclerotic; the most severe changes occur in the femoral
and popliteal arteries. The pulmonary arteries are usually almost free of
arteriosclerosis.
(From
textbook of Pathology, Bruce. Fallis, M. D. p394-396)
Obstructive emphysema
Obstructive emphysema is a chronic, usually progressive, largely irreversible pulmonary disease characterized by persistent overdistention of the lungs and gradual loss of pulmonary tissue . The pulmonary changes are diffuse but not always uniform and are caused by obstruction to air flow, especially during expiration. The obstruction to airflow is usually the result of chronic inflammation of the bronchial tree, and in England the term “chronic bronchitis ” is essentially synonymous with obstructive emphysema.
Obstructive emphysema is a very common disease and is found to some degree in about one-third of all autopsies. In England, where this disease is apparently somewhat more common than in the United States, “chronic bronchitis”is surpassed as a cause of death only by heart disease, cerebrovascular accidents, and cancer and constitutes the cause of 10 percent of all medical visits to general physicians. Obstructive emphysema is more common in men than in women (about 10:1), usually occurs after age 40, and is not definitely familial, although there may be a constitutional predisposition.
At autopsy in a case of obstructive emphysema the thoracic
cage is usually enlarged with an increased anteroposterior diameter (barrel
chest). The diaphragm may be hypertrophied, measuring up to 1cm in thickness,
and is usually low and flat. When the sternum is removed, the voluminous lungs
overfill the thoracic cage and bulge outward through the incision in the chest
wall. Extensive fibrous pleural adhesions are usually present. The lungs, after
removal from the chest, remain large and do not collapse. They are soft,
fluffy, relatively bloodless, and usually darkly pigmented by carbon. After
they have been transected, the lungs collapse and lie flat on the cutting
board, and the fact that pulmonary tissue has been lost is obvious.
(From textbook of Pathology,
Bruce. Fallis, M. D. p292-293)
Cirrhosis
Cirrhosis is a collective term,
which includes those chronic liver diseases in which hepatic injury is
associated with fibrosis of the liver. Cirrhosis is, thus, essentially
synonymous with chronic productive hepatitis. Cirrhosis is characterized
anatomically by (1) widespread but not necessarily uniform involvement of the
liver; (2) degeneration, necrosis, and usually regeneration of liver cells; and
(3) fibrosis of the liver, sometimes associated with partial or complete loss
of lobular architecture. Most cases of cirrhosis are progressive and terminate
in death due usually to failure of liver function or complications of portal
venous hypertension.
The classification of cirrhosis
is based on the anatomic changes in the liver. Unfortunately this anatomic
classification correlates only imperfectly with the incompletely known causes
of cirrhosis; i. e. , a given type of cirrhosis may have several different
causes, and the same factor may cause different types of cirrhosis under
different circumstances. The most important types of cirrhosis (with common
synonyms) are (1) portal cirrhosis (Laennec’s cirrhosis, alcoholic cirrhosis,
fatty nutritional cirrhosis; when the term cirrhosis is used without
qualification, portal cirrhosis is usually implied), (2) postnecrotic cirrhosis
(coarse nodular cirrhosis, healed yellow atrophy, posthepatitic cirrhosis,
chronic hepatitis), and (3) biliary cirrhosis (obstructive cirrhosis). Later in
the chapter a section is devoted to each of these types of cirrhosis. Uncommon
types of cirrhosis in the United States include cardiac cirrhosis (congestive
cirrhosis), the pigmentary cirrhosis of hemochromatosis, and zooparasitic
cirrhosis caused by the liver fluke or by schistosomiasis.
The cirrhotic liver is usually
abnormal in size, shape, consistency, and color, the exact changes varying with
the type of cirrhosis. The liver may be enlarged by an infiltration of fat or
other materials. On the other hand, progressive loss of parenchymal cells and
retraction of fibrous tissue lead to reduction of liver size. In a given case,
the liver may be enlarged early (“hypertrophic cirrhosis”), only to shrink
progressively as time passes so that the liver is small at the time of death
(“atrophic cirrhosis”). In some cases, the left lobe of the liver is injured
severely than the right and becomes disproportionately small, probably because
the left lobe receives nutritionally inferior blood from the splenic and
inferior mesenteric veins while the right lobe receives blood from the superior
mesenteric veins (this results from a “streamline flow” in the short portal
vein). Although the overall shape of the liver is usually retained, the
external and cut surfaces are usually nodular (hobnail liver) with projecting
masses of soft liver tissue separated by sunken bands of gray fibrous tissue.
Because of the increase of fibrous tissue, the liver is firm or hard and cuts
with increased resistance. The color of the cirrhotic liver varies and consists
of one or more of the following: red-brown (liver parenchyma), gray (fibrous
tissue), yellow (fat), and orange or green (bile).
(From textbook of Pathology,
Bruce. Fallis, M. D. pP353-354)
Peptic Ulcer
Peptic
ulceration occurs in the stomach and duodenum. Both acute and chronic forms are
founded, the latter being more common.
Clinical
Features. Approximately 10 per cent of the adult male populations are affected
by peptic ulceration. The male incidence is higher, the proportion being 3:2
for gastric ulcer and 10:1 for duodenal ulcer. Duodenal ulcers are three to
four times as common as gastric ulcers and most occur between the ages of 30
and 40 years, a decade or so earlier than gastric ulcers. In about 20 per cent
of the latter a duodenal ulcer is or has been present all in almost all
instances it precedes the gastric lesion.
The history is very important and
the diagnosis may often be made on to alone. Periodic epigastria pain occurs
after meals, discomfort from a gastric ulcer being noted half to one hour after
food whilst the stomach is still full, gradually passing off as the organ
empties, or relieved by vomiting. In a duodenal ulcer, a long post parricidal
interval of two to three hours offend exists before pain is apparent and it may
then occur immediately before next meal. Both food and alkalis relieve the pain
initally, although relief is greater in a duodenal than in a gastric ulcer.
Involvement of the pancreas may produce backache, which can mistakenly be
attributed to an orthopedic lesion. Nocturnal pain, at times sufficient to wake
the patient from sleep, is often a feature of a duodenal ulcer. Flatulent
dyspepsia may be the main symptom and aggravation by a fatty diet will
stimulate gall bladder disease. The appetite generally remains with loss of
weight. Lassitude and malaise may occur with secondary anemia from chronic
blood loss. Mental irritability is often prominent, but between attacks the
patient is usually eel and symptom free. Remissions, initially lasting months
or years, become shooter and the attacks more frequent. The latter may persist
for days or weeks and are often related to dietary indiscretion or periods of
intense worry or strain.
On examination the main physical
sign is tenderness in the epigastrium or right hypochondria, but between
attacks this may be absent.
Chronic Glomerulonephritis
Symptomatic chronic
glomerulonephritis is preceded by latent glomerulonephritis. In the
latent stage there are no symptoms, but the presence of slight hematuria and
proteinuria indicates the gradual progression of glomerular inflammation；the
blood pressure is normal at first but eventually becomes elevated. Latent
glomerulonephritis may heal but usually passes imperceptibly into chronic
glomerulonephritis. The clinical course of chronic glomerulonephritis is
characterized by the insidious onset of progressive，
irrevocable renal failure and hypertension. Hematuria and proteinuria occur but
are usually slight. About one patient in four will have one or multiple
exacerbations resembling acute glomerulonephritis，usually after a
streptococcal infection. The hypertension may become malignant，and
some degree of congestive heart failure is common. Death is due to uremia and
usually occurs in adolescence or early adult life，about one year after
the first symptoms of uremia.
In the history of patients with chronic
glomerulonephritis there may have been an initial attack of acute
glomerulonephritis，usually 5 to 15 years previously. However，many
patients with chronic glomerulonephritis give no history of acute
glomerulonephritis；it is unclear whether such cases represent a
different disease from those cases which begin with acute glomerulonephritis or
merely instances in which a mild acute glomerulonephritis was overlooked or
forgotten by the patient. A carefully taken history often reveals a partial or
complete nephrotic syndrome（see Membranous Glomerulonephritis and the
Nephrotic Syndrome）several years before the onset of chronic
glomerulonephritis.
At autopsy in a case of chronic glomerulonephritis the
kidneys grossly are very small (about 50 gm each)，especially in
long-standing cases in persons beyond adolescence. Each renal capsule strips
with great difficulty to reveal a coarsely granular，firm，very
pale，grayish white kidney.On the cut surface the renal
architecture is obscure，and the cortex is very thin. Microscopically the
changes are diffuse but not entirely uniform. Progressive hyalinization of the
glomerular tufts obliterates the glomerular capillaries，and
eventually the hyaline glomerulus fuses with the thickened glomerular capsule
to produce a small，pink，acellular ball. Such
hyaline globules may finally be resorbed，so that no trace of
the preexistent glomerulus remains. Because the peritubular capillaries arise
from the efferent glomerular arterioles，glomerular
hyalinization causes ischemic tubular atrophy involving most of the tubules.
There is severe interstitial fibrosis，both collapse and
productive in type，and the interstitial tissue is infiltrated by
lymphocytes. A few partially hyalinized glomeruli still contain some patent
capilaries and are only focally adherent to such glomeruli usually undergo
compensatory hypertrophy in an attempt to maintain renal function；they
are dilated，and their epithelial cells are large. Such hypertrophied
nephrons produce the coarse granules seen on the external surface of the kidney
grossly. Secondary vascular changes are caused by hypertension and consist of
arteriolosclerosis（hyaline or hyperplastic） or
arteriolar necrosis. Either benign or malignant nephrosclerosis may be
superimposed on the other renal changes. The type and severity of the vascular
changes depend on the severity and duration of the hypertension and the age of
the patient.
(From textbook of Pathology,
Bruce. Fallis, M. D. p489)
Tuberculosis (phthisis, consumption) is caused by Mycobacterium
tuberculosis. The tubercle bacillus is an aerobic bacterium, which grows slowly.
Within limits, an increased oxygen tension stimulates its growth, which is
perhaps a factor in its usual localization in the lungs. There are three strains
of Mycobacterium tuberculosis. Infection with the bovine strain is acquired
by ingestion of milk from infection cows, and most cases occur in children
with the initial lesions in the tonsils and cervical lymph nodes (scrofula)
or in the intestine and mesenteric lymph nodes. Infection with the bovine
strain is rare in the United States because of eradication of tuberculosis
in cattle and pasteurization of milk but constitutes about 10 per cent of
tuberculosis elsewhere. The avian strain rarely if ever causes progressive
tuberculosis in man. The human strain causes almost all cases of tuberculosis
in the United States, and the remainder of the discussion of tuberculosis
deals with this strain. Infection with the atypical mycobacterium is discussed
later.
The tubercle bacillus has a waxy cell wall which is in part
responsible for its acid-fast character (i. e. , it resists decolorization by
acids after having been stained by certain aniline dyes). The tubercle bacillus
is rich in phospholipid, and this lipid is apparently related to the
granulomatous inflammation and tubercles which occur in tuberculous lesions.
The protein fraction of the bacillus, tuberculoprotein, is evidently
responsible in some way for the development of bacterial hypersensitivity
during infection (see under Determinants of Tuberculous Lesions). Tubercle bacilli
produce neither an exotoxin nor an endotoxin, and tissue injury during
infection is dependent mainly on bacterial hypersensitivity.
The source of infection with the human strain is persons with
chronic pulmonary tuberculosis. Usually infection results from continued close
exposure to a tuberculous patient, e. g. , a household contact. Transmission is
by airborne bacilli. From the lung lesions the bacilli are expelled in droplets
by coughing. Although these droplets are, of course, infectious, they quickly
settle out of the air. However, the tubercle bacillus resists drying (but not
direct sunlight) because of its waxy cell wall and survives up to several
months in dried sputum. Dust from dried sputum is the chief source of airborne
bacilli and is the major vehicle of infection.
Tuberculosis is endemic in all
countries and is the most important chronic infectious disease. In 1900
tuberculosis was the most frequent cause of death in the United States. The
mortality rate of tuberculosis has declined for many decades primarily as a
result of an improvement in general living conditions in most countries. Better
methods of diagnosis, isolation, and treatment may have contributed to the more
rapid rate of this decline in recent years. Epidemiologic studies have not
clarified all the causes of long-term variations in the rate of tuberculous
mortality, but urbanization and substandard living conditions seem to be the
most important factors in increasing the rate.