Presentation: Chest Pain 2
Title: Chest Infections
Date & Time: Friday, January 25, 2008 at 9 AM
Lecturer: Ed Friedlander MD
QUIZBANK: Respiratory
Breakdown of the "Respiratory" quizbank items:
Introduction to Lung Pathology 1-42, 170-198
Interstitial Disease 235-249
Lung Cancer 199-234
Tobacco 43-65
Occupational Disease 150-169
Obstructive Disease 132-149
Infectious Disease 66-131
LUNG INFECTIONS
The airways of non-smokers are normally sterile below the vocal cords, but almost any organism capable of causing disease has caused pneumonia, infection of the lung substance.
Infections by the common bacteria most often cause exudation (edema fluid, then polys and maybe macrophages) into the alveolar spaces ("I'm coughing up icky stuff").
If the bacterial infection is confined to patches within individual lobes, it is called bronchopneumonia.
If the bacteria spread aggressively ("through the pores of Kohn"), stopping only for interlobar fissures, it is called lobar pneumonia.
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Viral and mycoplasma infections most often cause mild edema confined to the interstitium, and infiltration of the interstitium by lymphs and macrophages ("I've got a dry, hacking cough").
TB, pneumocystis, and fungal pneumonias each have distinctive pathology.
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{11435} cryptococcal pneumonia
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The terminology for all this is a little confused. Often "pneumonia" is used for inflammation in the alveolar air spaces, and "pneumonitis" is used for inflammation limited to the interstitium.
Lung infections are a common pathway out of life for people with disabling diseases of all sorts.
BRONCHOPNEUMONIA ("lobular pneumonia")
This patchy lung infection is ubiquitous in the hospital, and you will spend much of your time diagnosing and treating "pneumonia".
Why sick people get bronchopneumonia:
The anatomic pathology is nodules of edematous to hemorrhagic-purulent, patchy infected areas in the lung substance. Often easy to see, they are always easier to feel, being distinctly firmer than normal lung. You can even hear that there is less air.
Microscopically, the lesion is polys and fibrin nets in the air spaces. There is seldom much fibrin. (Important exception: E. coli pneumonias are mostly interstitial.)
Bronchopneumonia used to be a common complication of measles and whooping cough. Secondary bronchopneumonia caused by staph was a major killer in the 1918 influenza pandemic.
Pneumonic plague develops during plague outbreaks, and is transmitted person-to-person without requiring a rat flea. The virulence factor turns out to be plasminogen activator (think about it: Science 315: 529, 2007).
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{10148} bronchopneumonia (patchy)
{49076} bronchopneumonia
Though common, bronchopneumonia is an opportunistic infection, and patients are already sick with something that allows bacteria to gain a foothold.
Many people with bronchopneumonia have deficient gag and/or cough reflexes, from old age, anesthesia, drugs, pain, wasting diseases, paralysis.
If the cilia are not functioning optimally (hereditary dyskinesis, mild squamous metaplasia, cigaret smoking, irritant gas exposure, viral chest cold), it is hard to clear bacteria.
Alcohol and tobacco are noted for interfering with the ability of the alveolar macrophages to kill bacteria, and even oxygen therapy is supposed to be able to do this.
When secretions pool in the chest (bad chronic bronchitis, cystic fibrosis, or behind an obstructing cancer), bacteria have a great place to grow.
Edema fluid is a good culture medium, and it is common for a single clinical episode of bronchopneumonia to be series of infections by different organisms. It may begin as a pneumococcal infection, which is replaced by a H. 'flu infection, which is replaced by a klebsiella infection, which is replaced by a serratia infection. This probably explains most "antibiotic failures".
Aspiration pneumonia follows aspiration of gastric contents (or sometimes just food; in the newborn it can be meconium). Chemical injury plus mixed bacteria (from the mouth -- worst is a mouth is full of rotten teeth) cause a fulminant disease.
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Actually most bronchopneumonia cases are caused by bugs aspirated from the mouth.
The large majority of aspiration pneumonias are on the right side, and most often the right upper lobe is involved (why?).
* Fears that the "back to sleep" campaign for SIDS prevention would result in an increase in deaths from aspiration have proved unfounded (Pediatrics 109: 661, 2002).
* If you perform pulmonary lavage on a child with lung disease, you may be given the "lipid-laden macrophage index". This has been promoted recently as a marker for chronic aspiration; I am more willing to believe that it's less specific and just as likely to be the result of some alveoli being chronically obstructed (Eur. Resp. J. 18: 790, 2001).
Special cases:
{12638} vicious case of staph pneumonia
LOBAR PNEUMONIA
As noted above, this is an infection of an entire lobe
produced by a virulent micro-organism.
By far the most common etiologic agent has always been
Streptococcus pneumoniae
("pneumococcus", a gram-positive diplococcus called "captain of
the men of death", "the old man's
friend", etc.), which struck down healthy people in their prime
(Chest 99: 2, 1991). But this
organism is still easy to handle with antibiotics,
epidemics have become
rare, there's the vaccine, and few people die today of
pneumococcal pneumonia.
{27689} pneumococci in sputum; gram stain
Klebsiella pneumoniae ("Friedlander's pneumonia",
named by German pathologist Carl Friedlander whose
relationship if any to your lecturer remains unknown) causes lobar
pneumonia in deteriorated alcoholics. This gram-negative rod is
coated by a thick slimy capsule,
and victims cough up sticky slime ("cranberry sauce").
Staphylococcus
(after influenza), H. 'flu,
pseudomonas, and
others are notable causes of lobar
pneumonia in those with damaged lung defenses.
In the era when huge numbers of people died of pneumococcal
pneumonia, the classical anatomic
pathologists distinguished four successive stages of lobar
pneumonia:
1. Hyperemia and edema: the bugs divide like crazy, and
the blood vessels dilate and leak fluid in
response to injury. "Congestion", given in traditional accounts
of pneumonia, is an obvious
misnomer.
2. Red hepatization: the inflammation progresses, and
the damaged vessels now leak fibrinogen,
which forms fibrin meshworks in the alveoli. Some red cells are
released by damage to the blood
vessels, and polys come in to fight the bacteria. The alveolar
exudate becomes "rusty sputum".
3. Gray hepatization: fibrin dominates the picture,
while polys and red cells break down ("gray"
because hemorrhage is no longer taking place and the red cells
have lysed)
4. Resolution: plasmin clears out the fibrin, and the
lung returns to normal (hopefully).
COMPLICATION: The pleural surfaces overlying the infection are
almost always involved,
accounting for the pain of lobar pneumonia. There will be fibrinous
adhesions, which may resolve or turn
into scars.
COMPLICATION: In Klebsiella, staph,
or pseudomonas
lobar pneumonia, there is often necrosis
and abscess formation, which greatly complicates healing.
Necrosis is rare in pneumococcal
pneumonia (exception: the slimy type 3). More on this below.
{12641} staph producing abscess
COMPLICATION: If the infection gets really bad in the pleural
space, it will fill with pus
("empyema") and this will need to be drained. (This was the
most helpful
thing that a doctor could do for
pneumococcal pneumonia before penicillin.)
{49077} empyema
COMPLICATION: Sometimes the fibrin in the alveoli mostly
organizes instead, leaving a scar.
{39530} organizing pneumonia; balls of fibrin in
the alveoli
COMPLICATION: The bacteria often spread to other structures
(pericardial sac, meninges)
Today, uncomplicated lobar pneumonias are easily treated with
antibiotics once the etiologic agent
is identified.
{11431} lobar pneumonia
LEGIONNAIRE'S DISEASE (legionellosis, "Pontiac fever", etc.)
This is a special form of bronchopneumonia named for a lethal
outbreak at an American Legion
convention at a hotel in Philadelphia.
The etiologic agent is Legionella pneumophila. You
need special stains (immunostain or silver) to
see it.
The organism is common in standing water, especially in
air-conditioning systems.
Most healthy people merely experience a bad "chest cold", but
in older people who drink and smoke
heavily, it is likely to be fatal if
untreated.
{08179} legionella demonstrated with a silver
stain
NOTE: We are now recognizing that many cases of tough-to-treat
community acquired pneumonias
are due to CHLAMYDIA (Arch. Int. Med. 148: 1425, 1988),
notably the TWAR strain
("Chlamydia pneumoniae", Chest 95: 664, 1989; NEJM
323: 1546, 1990). These infections have
long been recognized in newborns, who acquire the more familiar
sexually-transmitted pathogen
from the birth canal. It's now a notorious, chronic, hard-to-eradicate
infection of the airways (J. Inf. Dis. 182: 1678, 2000; Am. J. Resp.
CCM 164: 536, 2001).
* NOTE: Untreated syphilis
in the mother can cause necrosis of the lungs
of the unborn child (Arch. Path. Lab. Med. 126: 484, 2002.
PNEUMOCYSTIS PNEUMONIA
This is a curious lung infection caused by a unicellular
organism (somewhere on the lineage that split to form protozoa and fungi),
Pneumocystis carinii (jirovecii).
It was originally identified as the cause of plasma-cell
pneumonia in malnourished children in
Europe at the end of World War II.
It is now familiar as a cause of pneumonia in AIDS patients
and people on cancer chemotherapy.
Instead of a plasma-cell pneumonia, these people show no
visible cellular reaction to the infection.
The organism and its cysts grow in the foamy exudate.
* As junior medical students,
we used to go to the airport to
pick up the pentamidine the CDC
shipped in every time we suspected pneumocystis. It was the only
thing that we knew worked. If you spend any time on the oncology service, you will
probably meet
pneumocystis (i.e., you will develop antibodies), but it can't hurt you as long as your T-cells are
working properly.
Future pathologists: You still need silver stains or immunostains
if you want to
identify pneumocystis with confidence. {0456} pneumocystis pneumonia
LUNG ABSCESS
Polys plus necrosis in a confined space (i.e., walled off by
granulation tissue) within the lung.
Mechanisms (after Baby Robbins):
1. Aspiration of bacteria (bad teeth, tonsils), as when drunk
or unconscious.
2. Complication of necrotizing pneumonia
(staph,
klebsiella,
pseudomonas, legionella) or
bronchiectasis
3. Obstructed bronchus (as, behind a cancer)
4. Infection within a lung cancer itself
5. Septic pulmonary embolus (leg vein infection, endocarditis,
and now an extremely common
problem of IV drug abusers -- Chest 94: 251, 1988)
6. Infarction of a pre-existing infection (as when a pulmonary
embolus hits an area of
bronchopneumonia)
Anaerobic bacteria are often present, and aerobes may also be
involved.
Sooner or later, the enlarging abscess ruptures into an
airway. The patient gets a worse cough and
bad breath, while the radiologist looks for air-fluid levels.
VIRUS RESPIRATORY DISORDERS -- MEET THE BUGS
These contagious diseases, typically spread by droplets, range from "the common cold" to deadly
viral pneumonitis.
By convention, upper respiratory infections involve the nose, sinuses,
throat, tonsils, and/or middle
ear. The anatomy is variable, and sinuses are often occluded. * CT scanners see NEJM 330: 25,
1994.
* Dost thou pray to thy god that thy nose may not run? Nay, foolish one! Thou blowest thy nose
on the sleeve of thy toga!
Lower respiratory infections involve the larynx, trachea, bronchi, alveoli ("viral pneumonitis",
"chest cold"), and/or pleura.
The anatomic pathology of a cold is what you'd expect.
If you were to biopsy the nasal mucosa in a common cold, you'd see abundant mucus production and
edema (hence, watery snot), and a preponderance of lymphocytes and plasma cells. Neutrophils
appear (and the snot turns yellow) when necrotic tissue
sloughs. (The "pop" wisdom is that the yellow mucus that occurs
late in a cold represents "bacterial superinfection"; do your own gram
stain and find out for yourself.)
In a typical viral interstitial pneumonitis, inflammatory cells fill the alveolar septa, but without
entering the alveolar spaces. (Absence of inflammatory exudate in the alveolar spaces distinguishes
"pneumonitis" from "pneumonia"; the distinction often blurs in practice.)
In fatal chest colds, we see similar changes, but with more florid cell damage. Death results when
the airways are sufficiently damaged to allow fibrin to escape and block air flow and exchange.
Failure of the airway to clear its secretions invites bacterial superinfection, with a neutrophilic
response.
A host of different viruses can be involved.
Rhinoviruses (>100 species), the usual agents of "the common cold" ("coryza", etc.), attack the
upper respiratory tract directly. They supposedly do not cause lower respiratory infections.
* "Stress & the common cold": NEJM 325: 606, 1991. Steam inhalation, Mom's favorite aid for the
common cold, is worthless (JAMA 271: 1112, 1994).
* Pleconaril, the new anti-viral agent that seems to be effective against
coxsackievirus (J. Inf. Dis. 181: 20, 2000) and the common
cold (Med. J. Aust. 175: 112, 2001).
Echinacea fails to help the common cold -- the conclusion of
a very elaborate, very expensive study (NEJM 353: 337 & 341, 2005)
which left the reviewers asking, "How much longer will we continue
funding studies of folk remedies when there is no plausable mechanism and
no demonstrable active substance?"
Coronaviruses (many species) are the second most common cause of the common cold.
The classic coronaviruses
supposedly do not cause lower respiratory infections, either. SARS is of course
a novel coronavirus infection (NEJM 348: 1977 & 1995, 2003).
Adenovirus (many species) can produce common colds, chest colds, red eyes ("epidemic
keratoconjunctivitis"), and/or GI upsets. Necrosis is typical of the most severe adenovirus
pneumonitis, which can be fatal (Arch. Path. Lab. Med. 113: 1349, 1989;
a bad case in an immunocompetent adult, which I suspect actually
happens fairly often Am. J. Med. Sci. 285: 285, 2003; the military must think so also
since it vaccinated against adenovirus from 1971 to 1999 and after cessation,
the disease re-emerged especially in recruits: J. Inf. Dis. 196:
67, 2007). Pathologists notice
enlarged, basophilic nuclei without any texture; these denote "smudge cells", typical of adenovirus
infection.
Disseminated adenovirus as cause of death in immune compromise: Am. J. Clin. Path. 120: 575, 2003.
{24371} adenovirus lung infection; low power shot just
shows thickening of the alveolar septa
Influenza (A, B, C; name is Spanish for "bad influence") is primarily an infection of any and all parts
of the respiratory tree. Update Nat. Med. 9: S-83, 2004
Systemic complaints begin 1-2 days after exposure, with fever, headache, myalgias, and fatigue. In
severe cases, necrotizing lesions of the airway appear.
Staphylococcal superinfection is common
and deadly.
Mutants vary their neuraminidase and hemagglutinin antigens, producing a new strain every few
years.
Influenza A: Pandemic influenza
Influenza B: Epidemics; children badly affected
Influenza C: Sporadic, upper respiratory infections
Tens of thousands of people die of influenza during every epidemic. The "flu shot" works great for
kids but only produces a 30% or so reduction in cases when used in nursing homes (abstract
92357998, from Italy). You already know about the 1918 epidemic of "Spanish flu",
which caused the greatest number of deaths of any infectious disease outbreak.
Forty million dead is a conservative estimate (Nat. Med. 10: S-83, 2004).
The mutation that triggered it: Science 293: 1842, 2001.
* The dread chicken flu in Hong Kong: Lancet 351: 467 &
472, 1998. Evolution of
new flu strains is blamed on agricultural practices in which chickens and
pigs are raised together.
* Recovering the virus and its genes from
bodies frozen in the Alaskan permafrost: Proc. Nat. Acad. Sci. 96:
1651, 1999. This is from the Armed Forces Institute of Pathology team
that succeeded in recovering the virus, which was also able simply to make
the recovery from old glass autopsy slides. The leader of
the rival group, which sought unsuccessfully to recover
the virus from a Norwegian burial, wrote the science-adventure book
"Hunting the 1918 Flu" (review NEJM 250: 352, 2004).
Parainfluenza viruses cause symptoms similar to influenza. Remember them as causes of
laryngotracheobronchitis ("croup").
Echovirus (* "enteric, cytopathic, human orphans"), an oral-fecal route pathogen that reaches the
other tissues via the bloodstream, produces sore throat and perhaps a rash ("exanthem"). It's also
linked to myocarditis.
Coxsackie virus A (* named for Coxsackie, N'Yawk) produces an annoying, blistering infection of
the throat, confusingly mislabelled "herpangina". It also produces the curious, usually-mild "hand, foot, and
mouth" disease (strains A15 and A16 and others including enterovirus 71;
blisters on hands, feet, and mouth;
Acyclovir therapy for coxsackie A: Cutis 57: 232, 1996.
Coxsackie virus B can involve the pleura (producing pleural pain, or "pleurisy"). It is also
implicated in both acute myocarditis and (as we have seen) in chronic immune-mediated myocarditis
("Barney Clark's disease").
Enterovirus 71 is one to watch. It caused a 1998 epidemic in Taiwan
with a devastating rhombencephalitis (NEJM 341: 929, 936, & 984, 1999).
Respiratory syncytial virus ("RSV"; NEJM 325: 57, 1991) causes epidemics of potentially-lethal
bronchiolitis and pneumonia in children (well-known, and rampant in hospitals
Clin. Inf. Dis. 31: 590, 2000) and debilitated adults (stay tuned). In fatal
cases, we see epithelial syncytia (i.e., fused, multinucleated cells) in the terminal bronchiolar
mucosa.
* Monoclonal antibody administered straight into the lungs to fight RSV: Proc. Nat. Acad. Sci. 91:
1386, 1994 (if we get a cure for the common cold it could be down these lines, but it's a long way
off).
* The famous RSV-vaccine fiasco -- previous "immunization" made the natural
infection worse.
Note that certain other viruses (measles,
mumps,
rubella,
chickenpox, etc.) enter the body by way of
the lungs. They may produce lung involvement during the clinical phase, but this follows spread of
the virus through the bloodstream.
NOTE: Mycoplasma pneumoniae, a little bacterium, is another very notable cause of chest colds,
probably more common than these viruses. More about this later.
VIRAL AND MYCOPLASMAL PNEUMONIA ("primary atypical pneumonia",
"chest cold", etc.)
A family of infections by micro-organisms smaller than
familiar bacteria, all causing interstitial
pneumonitis.
A while back, a group biopsied a bunch of folks with colds, and
found what you'd expect -- inflammation,
mostly lymphocytes, in the bronchial mucosa (Am. J. Resp. Crit.
Care Med. 151: 879, 1995).
Many annoying chest-colds are caused by Mycoplasma
pneumoniae (check blood for cold
agglutinins).
Viral infection of the lungs can be seen in measles (major
killer worldwide), influenza
(all strains),
chicken pox, adenovirus infection (look for "smudge cells"; this can cause
serious pneumonia even in healthy people, Am. J. Med. Sci. 325:
285, 2003).
Something that's getting more recognition lately is that
herpes simplex I is prone to erupt as a very serious pneumonitis
in patients on long-term mechanical ventilation.
Consider this the ultimate "stress lip blister." See Am. J. Resp.
Crit. Care Med. 175: 935, 2007.
Respiratory syncytial virus, once considered merely the usual
cause of "bronchiolitis" in toddlers,
is now known to be prevalent and
lethal among older adults. You should already be familiar with the multinucleated epithelial cells in the bronchioles.
* Interestingly, a vaccine was tried in the late 1960's and
proved to make the disease worse instead of
rendering the kids immune (J. Inf. Dis. 167: 553, 1993).
Puzzle that one out.
Metapneumovirus, a cause of wheezing mostly in youngsters,
was discovered in 2001 (Lancet 360: 1393, 2002; NEJM 350: 443 & 451, 2004).
Lethal influenza infection without staph superinfection presents
primarily as necrosis along the epithelium of the bronchi
and bronchioles. There may also be diffuse alveolar damage.
You will make the diagnosis by immunohistochemistry (Clin. Inf. Dis. 43: 132, 2006).
Unlike many other viral infections, there is no "trademark" histopathologic lesion.
Herpes simplex
can present as an ulcerative tracheobronchitis
in moderately immunocompromised hosts. Alternatively,
herpes simplex and herpes zoster can
both present as miliary hemorrhagic areas in the lung parenchyma
if immunosuppression is severe. Look for "herpes cells" with
a single intranuclear inclusion surrounded by a clear halo.
(* In contrast to skin and cervix, these viruses seldom
produce multinucleation in the lung.)
The nastiest infectious pneumonitis in the U.S. is the new
hantavirus, from inhaled mouse droppings
("Navajo pneumonia"; anatomic pathology Am. J. Path. 146:
552, 1995; review NEJM 330: 949, 1994). The virus specifically
damages the endothelial cells, producing an extreme pulmonary edema.
Distinctive for this
infection is an abundance of immunoblasts in lung
and peripheral blood.
SARS is a coronavirus: NEJM 348: 1977 & 1995, 2003.
The origin remains unknown; the original claim that it was a zoonosis
from eating wild animals didn't work out (Science 301: 1031, 2003).
The epidemic: Lancet 362: 1353, 2003.
Thankfully only about 1000 people died (follow-up Nat. Med. 9(s):
S-88, 2004).
The pathology (Lancet 361: 1773, 2003; Am. J. Clin. Path. 121: 574, 2004;
Hum. Path. 36: 303, 2005) features:
* The receptor for the virus in the lung is angiotensin converting
enzyme-2 (Nat. Med. 11: 875, 2005).
* Nobody knows how many nasty chest-colds are really zoonotic
Q-fever
(Coxiella). Probably underdiagnosed. Pathologists look for "ring / donut granulomas".
"Poker player's pneumonia", the scourge of one town,
was Q-fever traced to a cat's placenta (NEJM
319: 354, 1988).
In most cases of viral pneumonitis
that come to autopsy, the pathologist sees edema and
inflammatory cells, and the process is
confined to the interstitium.
The lungs are heavy but not airless (why not?) The inflammatory
infiltrate is mostly lymphs and
macrophages.
In severe cases, an ARDS picture supervenes, with hyaline
membranes.
* Lymphoid interstitial pneumonitis is a dense, polyclonal
("pseudolymphoma") infiltration
of lymphocytes strictly confined to the pulmonary interstitium,
usually in kids with AIDS or
adults with Sjogren's.
Don't confuse it with a virus.
Some patients have a low-grade clonal lymphomas,
which look identical; it's a spectrum (Chest 122: 2150, 2002).
{38402} bad viral pneumonia; the lung is nearly
solid from all the inflammatory stuff in the alveolar septa
Most patients recover without treatment. The most worrisome
thing about chest viruses for
healthy adults is that they predispose the lung to bacterial
superinfection.
You're already familiar with Kaposi's virus infection
("Kaposi's sarcoma") of the lung (Radiology
195: 545, 1995).
TUBERCULOSIS
("TB", "the white plague" -- covered twice in
R&F). Also here.
Primary tuberculosis occurs when the TB bacillus first infects a person.
A single lesion (the Ghon focus) occurs just under the pleura in the midportion (midway between
apex and base -- the best-ventilated area) of one lung.
The bacilli find their way to the regional lymph nodes, and in a few weeks, granulomas have walled
off the bacilli in both locations. (The combination of lesions in the lung and node is called the Ghon
complex). Viable bacilli remain in the Ghon focus/complex for life.
{08333} TB, lymph node
Much primary TB is asymptomatic, i.e., you discover you're turned your TB skin test.
Progressive
primary tuberculosis is the name given to overwhelming primary infection, which is not so rare
as we used to teach.
The classic dogma is that almost all progressive adult TB represents reactivation of a latent primary
focus. I have never understood why people believed this, and it turns out that it's clearly not true:
NEJM 330: 1697, 1703 & 1710, 1994 (at least in America's slums; confirmed NEJM 346:
1453, 2002; TB in immigrants does often seem to be reactivation). Only in 2002 did we get molecular
proof that one patient's TB had reactivated:
J. Inf. Dis. 185: 401, 2002. Primary or re-activated, the
pathology of bad TB is that of classic "secondary tuberculosis"....
Secondary tuberculosis ("active TB", "postprimary tuberculosis", "adult tuberculosis", "reinfection
tuberculosis", "cavitary tuberculosis") occurs when bacilli escape the original Ghon focus or
more bacilli enter the body from outside.
{08459} cavitary TB
The bacilli may be released from the Ghon focus by invading cancer or "by immunosuppression"
of some sort.
The infection usually reappears at the apex of one or both lungs ("Simon's foci" -- the TB bacilli
actually entered the bloodstream, but grow best in the lung apex where oxygen is most
abundant.) This is one cause of "white pneumonia" ("pneumonia alba"; the other is
syphilis).
The better the patient's cell-mediated immunity, the more classic the granulomas.
In other words, the worst TB cases in America today have very few, if any, granulomas! For
example, an AIDS patient can have lungs teeming with "red snappers" with only a sprinkling of
macrophages trying to fight them. (This patient may not even be very sick, but his ability to
transmit the infection is impressive.)
Polys are most abundant when the caseum has eroded into the large airways (why?). Also
remember that TB tends to calcify (handy for radiologists who want to tell it from cancer).
{05949} TB eroding through the chest wall
Arrested TB is secondary TB that has "calcified" and/or been largely replaced by collagen.
{11423} old TB
By contrast, progressive pulmonary tuberculosis spreads throughout the lungs and can produce a
"tuberculous empyema" by involving the pleural cavities.
When a large portion of the lung has undergone caseous necrosis,
extension into a large airway
causes all the debris to be coughed up -- exactly what the TB bacillus "wants", since this is how it is
transmitted to other people. The result is a cavity. (* Howler in R&F: "coin lesions" are lone
granulomas, not cavities.)
TB is also prone to infect the larynx and larger airways ("tracheobronchial TB") and, because bacilli
are swallowed, to affect the intestine (* look for Peyer's patches with ulcers having their long axes
perpendicular to the long axis of the bowel). Miliary TB results when many TB bacilli enter the bloodstream but the granulomatous response is
good. It is supposedly named for millet seed (parakeet seed -- * would anyone prefer "milli-",
meaning "thousands" of little granulomas?).
When TB ruptures into a pulmonary artery, there is miliary involvement of
part of a lung, while rupture
into a vein results in miliary involvement of the rest of the body.
When I have fears that I may cease to be
Keats went to medical school for a year and was
licensed as a physician and surgeon. He quit
to devote his life to writing poetry.
In this sonnet, he shares his fear that he may die before
had has time to get all his ideas into writing.
With his medical training, he had good reason to be afraid.
A few days before he wrote the poem,
he had experienced his first episode of hemoptysis. Three years
later he was dead of tuberculosis.
* Also good: Alexander Dumas Jr.'s Camille (TB is
glamorous), Eugene O'Neill's Long Day's
Journey Into Night (TB and drug addiction aren't glamorous),
1970's Italian film A Brief Vacation
(TB as social-political-feminist problem). I didn't understand
Thomas Mann's The Magic Mountain.
Reminder: In most chronic inflammatory diseases of lung,
clubbing of the nails ("Hippocratic
change") often develops because megakaryocytes embolize through
the new vascular channels formed in the lungs.
Infection by Histoplasma capsulatum, a tiny non-encapsulated (i.e., misnamed) yeast.
The organism is found primarily in the U.S., in the Mississippi River valley, and it is ubiquitous in
Kansas City. The organism is inhaled from bird (especially starling) or bat guano (caves are full of
it: JAMA 260: 2510, 1988), or from soil where these have been deposited. Only the spores
produced by the mycelium are contagious (i.e., you cannot possibly catch "histo" from a patient).
{10364} histoplasmosis in macrophages
When most people meet the histoplasma fungus, they develop only a mild fever and chest cold. If
the person goes to the doctor and gets a diagnosis, it is primary pulmonary histoplasmosis.
Latent histoplasmosis is the residue of an old, healed infection. Tiny calcified granulomas are found
in the lungs, and often in the spleen and even the liver. If you really looked, you'd probably find
tiny, old histoplasmosis lesions in a majority of autopsies in Kansas City. They may or may not
contain stainable or viable histoplasma.
Chronic pulmonary histoplasmosis is a cavitating, granulomatous disease of the lungs, while
disseminated histoplasmosis kills the immunosuppressed and those who, for some reason, cannot
mount an immune response. The diagnosis is generally a surprise at autopsy. "Histo" in AIDS: Am.
J. Med. 86: 141, 1989.
Single organ histoplasmosis has been reported for many locations, notably the adrenal glands (Ann.
Int. Med. 110: 87, 1989). A "histoplasmoma" is a calcified histoplasmosis granuloma, while
"sclerosing mediastinitis" is the result of serious histoplasmosis in the chest.
The similarity to TB should be obvious, and the pathogenesis ("histo" produces no tissue toxin but is
hated by the T-cells -- Am. Rev. Resp. Dis. 138: 578, 1988), gross pathology, and clinical pictures
are virtually identical. Histoplasmosis in AIDS: J. Inf. Dis. 158: 623, 1988.
Histoplasmosis endocarditis: South. Med. J. 100: 208, 2007.
Today, there's a urine test for histoplasmosis antigen that works
reasonably well (Am. J. Clin. Path. 128: 18, 2007.)
* Trivia: African histoplasmosis is caused by Histoplasma dubosii.
Infection by Coccidioides immitis,
an organism fortunately confined to parts of the U.S. southwest.
The fungus appears in tissue as a large spherule, often filled with endospores.
The infection most often takes the form of a severe chest cold with joint pains, but it proves lethal in
some cases.
Blacks and especially Filipinos are especially susceptible to this infection, and this was a major
killer of army recruits early in the 20th century. Navy
SEALs:
J. Inf. Dis. 186: 865, 2002.
Of course, other immunosuppressed patients are at extra
risk.
{24221} coccidioidomycosis
An opportunistic fungal infection by a yeast that abounds in pigeon droppings.
The yeast has a huge, gooey polysaccharide capsule (the basis for the India Ink test), and it
reproduces by narrow-based budding.
The most common site of infection is the meninges, and the underlying cerebral cortex may be
infected via the Virchow-Robin spaces and turned into swiss cheese.
Order a latex agglutination test on spinal fluid if you even vaguely suspect cryptococcosis.
Any other organ can be involved as well (* "crypto" of the prostate: Ann. Int. Med. 111: 125, 1989).
In the immunosuppressed patient, there is usually no inflammatory reaction, and the disease comes
on slowly.
Pneumonia
never mind the exotic bug...
Pittsburgh Illustrated Case
The new link is pseudomonas / aspergillus
and hyper-IgE SYndrome: J. Allerg. Clin. Imm. 119: 1234, 2007.
Lung Abscess
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
Suppurative pleuritis
Not quite empyema
WebPath
Future radiologists: It is often impossible to tell these from
cancers on screening scan. ("This looks like bronchiolo-alveolar to me!":
Radiology 245: 267, 2007).
{11732} lobar pneumonia
{11733} lobar pneumonia
{11734} streptococci in lobar pneumonia,
gram stain
{12464} lobar pneumonia
{17565} lobar pneumonia
{17567} lobar pneumonia
Pneumocystis
Lung pathology series, great photos
Dr. Warnock's Collection
--Epictetus
* Adenovirus hepatitis after bone marrow transplant:
Arch. Path. Lab. Med. 127: 246, 2003.
{24374} adenovirus lung infection; hyaline membranes;
no visible smudge cells but lots of lymphocytes
{01743} smudge cell, schematic diagram
Adenovirus of the kidney
Advanced students
Yutaka Tsutsumi MD
* Not to be confused with
the dread foreign zoonosis, "hoof/foot and mouth disease"; see above.
RSV
WebPath Photo
Viral lung infection
Lymphocytes
WebPath Photo
As we've seen, it's now pretty clear that mycoplasma, chlamydia, and
probably other little bugs that are hard to grow in the lab are colonists
in asthmatic airways and contribute to the problems (J. Imm. 179:
3995, 2007).
Adenovirus pneumonia
Can you find smudge cells?
Yutaka Tsutsumi MD
Measles pneumonia
Can you see the measles cells?
Yutaka Tsutsumi MD
Influenza
Yutaka Tsutsumi MD
Measles pneumonia
Yutaka Tsutsumi MD
CMV pneumonia
Yutaka Tsutsumi MD
Herpes simplex pneumonia
Yutaka Tsutsumi MD
Varicella-zoster pneumonia
Yutaka Tsutsumi MD
The "bird flu" is so dreaded since (like SARS) it attacks primarily
the alveolar epithelium and causes ARDS. "Bird flu" produces more necrosis
and less fibrosis than SARS (Hum. Path. 37: 381, 2006).
Respiratory syncytial virus
Bad pneumonitis
WebPath
Respiratory syncytial virus
Syncytia
WebPath
Viral Pneumonia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
Lymphocytic interstitial pneumonia
Pittsburgh Pathology Cases
Kaposi's in the lung
Lung pathology series
Dr. Warnock's Collection
Tuberculosis
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
Tuberculosis of the lung
Classic drawing
Adami & McCrae, 1914
You are already familiar with how TB causes tissue injury.
(Click here for a review.)
Tuberculosis
Very large Ghon focus
WebPath Photo
{08336} TB, lymph node
{10230} TB in the lung, good cavity
{21151} disseminated, miliary TB in liver
TB
WebPath Photo
Tuberculosis; white pneumonia
Lung pathology series; follow the arrows
Dr. Warnock's Collection
{08187} TB, kidney
{08188} TB, lung
{08190} TB, lung
{08193} TB, lung
Before my pen has gleaned my teeming brain,
Before high-piled books, in charactery,
Hold like rich garners the full-ripened grain;
When I behold, upon the night's starred face,
Huge cloudy symbols of a high romance,
And think that I may never live to trace
Their shadows, with the magic hand of chance;
And when I feel, fair creature of an hour,
That I shall never look upon thee more,
Never have relish in the faery power
Of unreflecting love! -- then on the shore
Of the wide world I stand alone, and think
Till Love and Fame to nothingness do sink.
{06065} histoplasmosis
{06068} histoplasmosis
Ghon focus; histoplasmosis
Lung pathology series
Dr. Warnock's Collection
COCCIDIOIDOMYCOSIS
("San Joaquin Valley fever") NEJM 332: 1077, 1995
Most famous for occurring in the San Joaquin valley of central California,
a variant strain is very abundant in the Phoenix-Tucson area of Arizona.
{24224} coccidioidomycosis
Cryptococcosis
Infection in Virchow-Robin spaces
KU Collection
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BLASTOMYCOSIS
("blasto", "North American blasto", "Chicago disease"): JAMA 261: 3159,
1989; Lancet 1: 25, 1989 (still good); South. Med. J. 92:
289, 1999.
Infection by Blastomyces dermatitidis, a yeast found primarily in the Mississippi River valley, especially on riverbanks.
Recognize these yeasts by their large size, thick walls and single, broad-based buds. One good way to catch the bug is to mess around in a beaver dam. Subclinical infection is now known to be common, though not nearly so common as histoplasmosis (Am. J. Med. 89: 470, 1990).
The host response is generally a mix of suppuration and loose granuloma formation.
Skin infections (for some reason considered to be "always secondary to lung infection") feature a chronic dermatitis, with overgrowth of the epidermis ("pseudoepitheliomatous hyperplasia") that will almost always be mistaken clinically for cancer.
Making the diagnosis is tricky. Culture will take about 5 weeks, so cytology (brushings, washings) plus serology are probably in order whenever you are trying to diagnose "pneumonia" or "lung cancer" (Chest 121: 768, 2002).
"Blasto" is a primary infection, and not much seen in immunocompromised patients; it is now turning up as a pathogen in AIDS. It responds poorly to anti-fungal drugs, though some infections have been successfully treated.
* It is a common cause of death in pet dogs.
* Its known virulence factor (BAD1) causes macrophages to pump out lots of TGF-β and thus suppress their own production of TNF-α: J. Immunol. 168: 5746, 2002).
{00443} blastomycosis in tissue
{10667} blastomycosis in the lung (my case)
{00460} blastomycosis in AIDS patient (fungus is black)
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A fungal infection caused by a huge yeast, Paracoccidioides brasiliensis, that produces many spores
at the same time ("multiple buds", "mariner's wheel").
{24491} South American "blastomycosis" of the face
Most victims are male agricultural workers, especially in the Amazon basin. The victim usually has
picked his teeth with a piece of jungle wood. (The common claim, repeated in "Big Robbins", that
oral lesions have spread from the lungs seems silly to this pathologist.) The mouth, and sometimes
the lungs, are the usual sites of involvement.
* Women during child-bearing years are immune, since estrogens turn the yeast into a
non-pathogenic hyphal form.
Invasive fungus infection, usually by Aspergillus fumigatus or niger, the familiar, ubiquitous fungi
with septate, narrow-angle branching hyphae and characteristic fruiting bodies (* which resemble a
holy water sprinkler used by some denominations -- "aspergillum"). More pathogenic than mucor,
it also invades blood vessels.
"Big Robbins" describes "colonizing aspergillus (aspergilloma)" as if it were a wad of harmless
fungus growing in an old TB cavity. Since these lungs often have no other evidence of previous TB,
and since these patients do cough up blood, it seems more likely that the fungus has invaded a blood
vessel, then colonized the ischemic tissue.
Everyone believes in invasive aspergillosis, a common, life-threatening, hard-to-diagnose infection
among the immunosuppressed.
* Is nothing safe? Aspergillus and other horrid fungi
from taking a shower Cin. Inf. Dis. 35:
E86, 2002. Does make sense. Also fusariosis Clin. Inf. Dis. 33:
1871, 2001.
{00413} aspergillus, brain
People also get allergic to aspergillus, i.e., to airborne spores, which can produce type I (asthma),
type III (organic pneumoconiosis), and/or type IV (more organic pneumoconiosis) immune injury.
Of course, people can and do become allergic to their own infectious agents, and people who already
have fungus balls tend to become allergic to them. And aspergillus commonly infects people who
already have allergic asthma. Both are called allergic aspergillosis (Postgrad. Med. J. 64 Supp. 4:
96, 1988).
* Aspergillus flavus produces aflatoxin, the famous carcinogen.
Histoplasmosis and blastomycosis
Lung pathology series
Dr. Warnock's Collection
PARACOCCIDIOMYCOSIS
("South American blastomycosis")
There are several different tissue reactions, depending on how
immunocompromised the patient is. Macrophages tend to attack the spores,
while neutrophils attack the hyphae (Am. J. Clin. Path. 127: 349, 2007).
{06077} aspergillus, brain
{06085} aspergillus, vessel; silver stain
{10670} aspergillosis, lung
{10673} aspergillosis, lung
{11018} aspergillosis, lung; silver stain
{37661} aspergillosis, brain
Aspergilloma
Lung pathology series; follow the arrows
Dr. Warnock's Collection
Hyphal fungi and candida
Lung pathology series
Dr. Warnock's Collection
Lobar pneumonia
Bronchopneumonia I
Pneumococcal pneumonia
Pneumocystis carinii
Tuberculosis
HISTOPLASMOSIS ("histo")
Blastomycosis