This site complies with the HONcode standard for trustworthy health information: verify here. |
Cyberfriends: The help you're looking for is probably here.
This website collects no information. If you e-mail me, neither your e-mail address nor any other information will ever be passed on to any third party, unless required by law.
This page was last modified January 1, 2016.
I have no sponsors and do not host paid advertisements. All external links are provided freely to sites that I believe my visitors will find helpful.
Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.
I am active in HealthTap, which provides free medical guidance from your cell phone. There is also a fee site at www.afraidtoask.com.
If you have a Second Life account, please visit my teammates and me at the Medical Examiner's office. |
With one of four large boxes of "Pathguy" replies. |
I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
pathology.org -- my cyberfriends, great for current news and browsing for the general public
EnjoyPath -- a great resource for everyone, from beginning medical students to pathologists with years of experience
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
still handling dozens of requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
During the eighteen years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at William Carey
for making it still possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
KCUMB Students
Public Database of Human Cancers -- World Health Organization
Stanford Surgical Pathology Criteria -- probably the best resource for the practicing surgical pathologist in an increasingly difficult specialty
Medscape Pathology -- mostly clinical medicine, the best "daily news" of the medical world
Pathology Resident Wiki
Human Pathlogy -- growing resource
Surgical Pathology Atlas -- lots of photos
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Pathopic -- Swiss site; great resource for the truly hard-core
Alabama's Interactive Pathology Lab
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
Karolinska Institutet -- pathology links
Johns Hopkins CPC's
Oklahoma Teaching Cases
Indiana U. Teaching Cases
SUNY Histopathology
West Virginia Case of the Month
Society for ultrastructural pathology -- electron microscope cases
PathologyPics -- where pathologists share favorite images. Thanks!
WebPath:
Internet Pathology
Laboratory -- great siteEd Lulo's Pathology Gallery
Also:
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Medmark Pathology -- massive listing of pathology sites
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
Learning objectives
Recognize the common porphyrias. Suspect porphyria when appropriate,
order the right tests,
and collect the specimens properly.
"Big Robbins" -- RBC / Bleeding
Lectures follow Textbook
QUIZBANK... Metabolic #'s 112-114
Porhpyria Registry -- good Yahoo! group
European Porphyria Initiative |
Porphyria images
|
PORPHYRIAS AT A GLANCE:
DEFICIENT ENZYMES | DISEASES |
* ALA synthetase (turns glycine + succinic acid into ALA) | (rare porphyria) |
* ALA dehydratase / ALAD (turns ALA into PBG) | (rare , J. Clin. Invest. 89: 1431, 1992; Blood 97: 2972, 2001; seven cases reported to date, remember that porphobilinogen will not be increased) |
Porphobilinogen deaminase (uroporphyrinogen I synthetase) (turns four PBG's to UroI) | acute intermittent porphyria |
* Uroporphyrinogen III synthetase (turns four PBG's to UroIII) | congenital erythropoietic porphyria |
Uroporphyrinogen III decarboxylase (turns UroIII to CoproIII) |
porphyria cutanea tarda (one dose, mild) / * hepatoerythropoietic porphyria (two doses, severe) |
* Coproporphyrinogen III oxidase | coproporphyria |
Protoporphyrinogen III oxidase (turns CoproIII to ProtoIII) | variegate porphyria |
Ferrochelatase (puts the iron into ProtoIII) | (erythropoietic) protoporphyria |
INTRODUCTION New porphyrias continue to be described (* for example, a coproporphyria
variant with severe hemolysis: Blood 91: 1453, 1998).
The porphyrias must be the most-hated diseases
in medicine.
* This unit will focus on what a general physician needs to know about the porphyrias. DO NOT go
back and memorize the porphyrin section of Stryer!
* Dividing porphyrias into "hepatic" ("caused by accumulation of precursors of the P450
cytochrome") and "erythropoietic" ("caused by accumulation of precursors of hemoglobin") is
becoming unfashionable.
Despite the problems making porphyrins, the metabolic machinery goes into overdrive
so patients are seldom anemic.
All about the LAB DIAGNOSIS of porphyrias:
NEJM 324: 143, 1991; update J. Clin. Path. 54: 500, 2001. Diaper diagnosis of erythropoietic porphyria (all you need is a diaper and a
hippie's ultraviolet light): NEJM 330: 119, 1994. Porphyria in children:
Mayo Clin. Proc. 77: 825, 2002 (kids); Am. J. Clin. Path. 119(S): S-86, 2003.
MECHANISMS AND SYMPTOMATOLOGY IN THE PORPHYRIAS
{09199} porphyria
Most current thinking focuses on accumulations of toxic metabolites.
DELTA-AMINO LEVULINIC ACID and PORPHOBILINOGEN
are neurotoxins that produce cerebral dysfunction
and damage (confusion, "psychiatric disease", depression, anxiety,
hallucinations, paranoia), autonomic neuropathy (vomiting, constipation, urinary
retention, tachycardia, hypertension, often atrial fibrillation -- Am. J. Card. 104:
373, 2009), severe (sometimes chronic) abdominal pain, and (often) hyponatremia from
inappropriate hADH secretion.
These porphyrias imitate other many diseases, from acute appendicitis to acute schizophrenia.
Between attacks, patients have mild symptoms, including "psychoneuroses". Obviously, making the correct diagnosis is important. (Up to 1 in 300 psychiatric patients
has AIP as their main problem.)
Delta-amino levulinic acid may be a false transmitter for gamma-amino butyric acid. It also blocks
one of ATP-ases (perhaps a sodium pump) in nervous tissue.
The damage to the peripheral nerves caused by the porphyria neurotoxins
is not reversible when the acute attack ends. Many of these people end up with
chronic severe pain and weakness. On nerve biopsy, findings are nonspecific; the axons
are selectively damaged rather than the myelin.
Urine rich in porphobilinogen turns reddish-purple (uroporphyrin) on long exposure to bright light
(toilet, ward station, lab). "Porphyria" means "purple".
UROPORPHYRINOGEN (mostly in the cytoplasm) when exposed to ultraviolet light generates free radicals.
The worst wavelength is 400 microns (* "the Soret band", responsible
for the orange-red fluorescence), which is not screened out by window glass or standard sun-screens. These patients need
to use opaque stuff on their skin. Beta-carotene, which absorbs the
problem photons, is another mainstay of
their therapy but nobody knows how well it actually works.
Patients with these porphyrias suffer blistering (subepidermal
separation) and scarring of the skin. Look especially on the
backs of the hands.
For some reason uroporphyrinogen also causes increased lanugo hairs ("hypertrichosis"). Look
especially over the cheeks and temples.
PROTOPORPHYRIN IX (mostly in the mitochondria and red blood cells) generates free radicals too.
Other current ideas about how porphyrias cause symptoms focus on the actual
LACK OF HEME MOIETIES IN TISSUE. This is difficult to study but makes sense.
ACUTE INTERMITTENT PORPHYRIA (AIP -- see Neurology
48: 1678, 1997)
This autosomal dominant disorder is due to a partial deficiency of uroporphyrinogen I synthetase
(porphobilinogen deaminase). It is a disease of flare-ups that will baffle anyone
who doesn't consider it.
To make the definitive diagnosis, you can measure the level of the enzyme in RBC's to detect even latent AIP.
This is now the preferred means of making the diagnosis; of course, you need a
specialty lab.
* By now, a host of different alleles are known, and which type is
present correlates with severity (Medicine 84: 35, 2005).
The disease is most common in Sweden due to a founder effect.
* The homozygous form is of course a disaster: Neurology 61: 1764, 2004.
During acute episodes, the patient typically has severe colicky
ABDOMINAL PAIN and/or "PSYCHIATRIC DISTURBANCES". Most are tachycardiac (helpful in following the illness), and hypertension and
leukocytosis are common.
MRI scans show vascular mayhem in the brain in acute intermittent porphyria (Neurology 41: 1300,
1991).
* Poe's Roderick Usher ("Fall of the House of...") was perhaps based on someone with acute
intermittent porphyria (JAMA 261: 863, 1989). UMKC's Loretta Loftus et. al. suggests porphyria
as the cause of Vincent VanGogh's craziness (Br. Med. J. 303: 1589, 1991).
Especially suspect AIP whenever a patient has suggestive signs after taking
BARBITURATES (which
increase ALA synthesis).
Oral contraceptives, sulfa drugs (sulfonamides), ketoacidosis,
cocaine (Lancet 2: 1150, 1987), fasting, and acute infections also
precipitate attacks. (These patients need a Medi-alert bracelet.)
* Mathilde Schleicher, one of Freud's first patients,
developed psychosis,
abdominal pain, constipation, and red-purple urine. Freud recognized quickly
this was medical disease and referred her to the internists; unfortunately she
was killed by a dose of an old sulfonamide.
The BASIC SCREENING TEST FOR AIP is URINARY PORPHOBILINOGEN. (ndications for this test includes elements of
the clinical picture outlined above. Be suspicious! One patient in 1000 has at least the genetic
potential to express AIP.
Urine porphobilinogen will be increased during acute episodes (at least) of AIP (* also variegate
porphyria and coproporphyria.)
* Theoretically, the urine "dipstick" test for urobilinogen should record porphobilinogen, too. This
just doesn't work in practice,
because porphobilinogen is very unstable and there's not enough to turn color anyway.
You must collect the urine for porphobilinogen assay in a
LIGHT-PROOF BOTTLE (wrap it in aluminum
foil.) Alkalinization is no longer strongly recommended.
Most important, the urine must be REFRIGERATED.
Even if you see purple urine, get confirmation on a super-fresh or very-well-refrigerated
specimen.
* The traditional
screening tests for porphobilinogen are extraction-based
traditional-bench-chemistry tests
called the "Watson-Schwartz" and "Hoesch" tests, and you may
hear these names.
These are NOT sufficiently sensitive for routine
screening (Am. J. Clin. Path. 92: 644, 1989).
Today's lab will use high pressure liquid chromatography to screen
for delta-amino levulinic acid and porphobilinogen.
* If you need further tests to establish the diagnosis of acute intermittent porphyria, get consultation.
You may order urinary uroporphyrin (will be high), urinary delta-amino levulinic acid, and/or red
cell porphobilinogen deaminase (detects the latent illness).
You may also discover the patient has inappropriate hADH production and increased thyroid
binding globulin, though this is not part of the work-up.
* You will learn how to treat acute intermittent porphyria on rotations. Specific remedies
have included heme derivatives plus
glucose. Both inhibit the synthesis of amino-levulinic acid.
Today's "Panhematin" is hemin, an iron-containing porphyrin and
generally recognized as effective (Am. J. Med. 119: 801.e19, 2006 --
bewails the ongoing problem of missed diagnoses).
Liver transplant for cure: Lancet 363: 705, 2004.
* Recently a considerably increased incidence of hepatocellular carcinomas
in acute intermittent porphyria patients in Sweden got noticed (J. Clin. Path. 65: 976, 2012).
What might be the reason?
VARIEGATE PORPHYRIA
This disease, similar in symptoms to AIP but with photosensitization as well,
may perhaps have afflicted the European royal families --
King James (Bible Version), George III (American revolution, update Lancet 366:
332, 2005 supports the claim and also finds arsenic from quack treatments in
his hair, which has toxicities that mimic porphyria), Mary Queen of Scots, and others all
had symptoms (but who hasn't had belly pain and/or been a little crazy?),
and some of their living descendants do have variegate porphyria (case for porphyria: Br. Med. J. 1: 7, 1968;
case against porphyria J. Clin. Path. 65: 200, 2012).
Your lecturer is undecided.
To make this diagnosis, measure protoporphyrinogen oxidase after puberty
(S. Afr. Med. J. 70: 819,
1986 -- this disease is very common in South African whites because of a founder effect).
Gung-ho clinicians now aspirate
duodenal bile or cannulate the common bile duct to measure bile porphyrins
(* protoporphyrin is soluble in bile but not in urine),
establishing the
diagnosis between attacks (NEJM 324: 1432, 1991, works great). Homozygotes are severely
affected (Clin. Genet. 32: 300, 1987).
COPROPORPHYRIA
Deficiency of coproporphyrinogen oxidase. This fortunately rare disease is similar to AIP, and tends
to produce a bad neuropathy and a noxious pain syndrome.
* Part of the mythology of "multiple chemical sensitivities"
is that it is forme fruste of coproporphyria. This obviously
doesn't make sense, and
the lab that popularized the diagnosis was using a
flawed assay: Arch. Int. Med. 157: 281, 1997.
More about "MCS", later, along with why almost no one in scientific medicine
believes in it any more, and how its proponents operate. PORPHYRIA CUTANEA TARDA (familiar as "PCT"; Medicine 89: 69, 2010)
This commonest of the porphyrias is due to a partial deficiency of uroporphyrinogen
decarboxylase. (Molecular biology: Blood 88: 3589, 1996). Uroporphyrinogen is elevated
in the urine, enabling the diagnosis. It announces itself
as scarring from sun exposure, and perhaps extra hair (especially on the cheeks).
The disease may be inherited, OR one or more liver problems may cause sufficient
deficiency of the enzyme to create an acquired illness. Here's the classification:
Because it usually expresses itself only in the setting of iron overload
or chronic liver disease, it is hard to decide where "familial" ends and
"multifactorial, like most other diseases" begins.
Unless the deficiency is very severe (the rare, recessive familial PCT), it manifests only if there is
also systemic iron overload (i.e., hemochromatosis, older drinkers heterozygous for
hemochromatosis, with thal minor, or on dialysis -- Nephron 60: 428, 1992, or with sideroblastic
anemia). As you might guess, iron further inhibits the enzyme. The mainstay of treatment is
removing iron from the body.
The plot thickens even more... porphyria cutanea tarda from whatever
cause down-regulates hepcidin, the liver iron-handler. This
probably explains everything (Blood 112: 4723, 2008).
Alcohol also inhibits the enzyme, and acute episodes often follow a drunken spree.
Still other patients have smoldering hepatitis C (South. Med. J.
90: 872, 1997) and/or HIV infections
as the trigger (Arch. Derm. 132: 1448, 1996; even in the absence
of sickness, HIV often raises the urine and stool levels of porphyrins as
in PCT (Arch. Derm. 132: 1443, 1996). Review:
Mayo Clin. Proc. 73: 895, 1998.
I'd suggest screening all your young PCT patients.
* Aluminum, in old-time uremic patients on dialysis, also caused PCT.
Cool finding: Because the urine is loaded with uroporphyrin,
the urine is likely to be reddish or brownish, and if
you have a fluorescent light handy, it will glow pink. There's a lot
of PCT out there, and the fluorescent light trick
will make you look and feel clever. (See Postgrad. Med. 105:
208, 1999).
{12141} porphyria cutanea tarda
* Future pathologists: Liver biopsy specimens from patients with this disease are fluorescent
due to the uroporphyrin crystals.
* Homozygous PCT is a much more serious disease; you may hear it called "hepatoerythropoietic
porphyria". Assaying the enzyme won't tell you which is which, y'gotta examine the
patient... Am. J. Med. Sci. 315:59, 1998. Year-long "child abuse" ordeal for
parents of sibs with the disorder ("I know what that is, these are old cigarette burns!!!") --
Arch. Derm. 146: 529, 2010.
The main problem is SKIN PHOTOSENSITIVITY with increased tanning, blistering, scarring, especially the
backs of the hands. There is often hypertrichosis.
The histopathology features separation of epidermis and dermis, without inflammation,
and with preservation of the shapes of the dermal papillae. No one really understands
how this happens.
The BASIC LAB TEST today is getting a PLASMA FLUORESCENCE SCAN across the spectrum.
Order it when you see suspicious skin lesions. (The peaks will also tell you
whether it's PCT or variegate porphyria).
* To screen a relative for latent PCT, you can
test for erythrocyte uroporphyrinogen decarboxylase (Clin.
Chem. 34: 2355, 1988).
(ERYTHROPOIETIC) PROTOPORPHYRIA
Deficiency of ferrochelatase, the enzyme that inserts iron into the completed heme ring.
The troublesome allele identified: Blood 93: 2105, 1999; how the mutations
work Blood 96: 1545, 2000.
Because of the protoporphyrin IX, these people complain of burning pain a few minutes after ultraviolet light exposure.
Protoporphyria is rather common and of variable expressivity.
Series Arch. Derm. 143: 1125, 2007.
This is primarily a photosensitivity syndrome, with beta-carotene the mainstay of treatment.
A small minority of proroporphyria patients
get liver damage (sometimes even cirrhosis) from porphyrin crystals that accumulate
in the hepatic parenchyma. (Successful transplant: Gastroenterology 98: 816, 1988.
Nowadays, we transplant marrow and liver at the same time -- why?)
An easy way to help make the diagnosis is by noting the red fluorescence of the erythrocytes.
We recommend ordering a RED CELL PROTOPORPHYRIN IX assay for screening.
You'll make the definitive diagnosis by enzyme assay.
* The ultra-rare X-linked dominant protoporphyria is due to a gain-of-function
mutation in delta-ALA synthetase 2 (Am. J. Hum. Genet. 83: 408, 2008).
CONGENITAL ERYTHROPOIETIC PORPHYRIA (* Gunther's disease)
This a rare autosomal recessive disorder with a lack of uroporphyrinogen III synthetase. Gene
cloned: Hum. Genet. 88: 320, 1992; molecular biology J. Clin. Inv. 107:
753, 2001; forme fruste Arch. Derm. 128: 1243, 1992 and Arch. Derm. 141:
1575, 2005; unusual genetic variant
Blood 109: 2618, 2007.
There are crystals in RBC's that cause hemolysis.
Today, bone marrow transplantation, if available, is curative.
The most severe forms might have given rise to
stories about vampires and werewolves:
An inbred mountain community (say, in Transylvania)
may have had a large cluster of these unfortunates.
See also Dragon 131: 8, 1988.
Consider additional factors behind the stories. Violent behavior transmitted by bite:
Rabies.
"Fresh"
blood on the mouth and in the throat of a corpse following burial: Bloody purge of decomposition.
The normal slippage of the epidermis after death, described in some exhumation accounts,
was interpreted as the vampire shedding its skin like a snake to regain
its strength. The groan emitted by the corpse when it was "staked"
was escaping gases of decomposition. * Bone marrow transplantation is curative: J. Ped. 129: 453, 1996;
Blood 92: 4053, 1998; Blood 109: 2618, 2007.
Gene therapy cures a tissue culture: Blood 85: 1449, 1995.
Congenital erythropoietic prophyria
Congenital erythropoietic prophyria The diagram is simplistic -- PCT can show the perivascular PAS-positive stuff, and of course
erythropoietic protoporphyria can blister.
ACQUIRED PORPHYRIAS AND PSEUDOPORPHYRIAS
The most important "acquired porphyria" (a term passing out of use) is
LEAD POISONING, which simulates acute intermittent
porphyria (abdominal pain, insanity, etc). Lead ion inhibits delta-amino levulinic acid dehydratase
(porphobilinogen synthetase; Am. J. Ind. Med. 32: 15, 1997),
ferrochelatase (the enzyme that puts the iron into the heme ring when it is finished), and other
enzymes.
During the 1980's, we looked for low delta-amino
levlinic acid dehydratase levels in erythrocytes to screen.
Erythrocyte zinc protoporphyrin (increased) and urinary delta-amino levulinic acid (increased) are
were also useful, sensitive procedures. Free erythrocyte protoporphyrin then became standard.
However, the EPA lowered the acceptable levels in the late 1990's (thanks for once), and
everybody now uses direct assay of atomic lead, using a
special LEAD-FREE CONTAINER. The birth of the lead-free vacutainer tube:
Clin. Chem. 45: 148, 1999.
Mercury and arsenic are other heavy metals that will change the porphyrin patterns.
Industrial poisons (notably polychlorinated benzene: Arch. Env. Health 54:
248, 1999) have caused and will cause outbreaks of
acquired porphyria by interfering with heme metabolism.
As you might expect, the iron chelator
desferrioxamine produces an acute porphyria. * A host of drugs (some noted photosensitizers, some not)
cause a rash like that of PCT ("pseudo-porphyria" or the badly-named "acquired PCT")
in "predisposed" people. Lab porphyrin and enzyme values remain normal.
Biopsy findings are identical to PCT.
This "pseudoporphyria" may be hard to reverse even after discontinuation
of the offending medicine (Mayo Clin. Proc. 76: 488, 2001).
How this happens is still mysterious.
REMEMBER: Acute intermittent porphyria can simulate most neurologic and psychiatric diseases,
including "drug-seeking malingerers" complaining of atypical pain.
* Anesthesia for the porphyria patient: Anesth. Analg. 80:
591, 1995; gabapentin for seizures seems safe Neurology 46: 1497, 1996.
BIBLIOGRAPHY / FURTHER READING
I urge anyone interested in learning more about
the porphyrias
to consult these standard textbooks.
In my notes, the most helpful current
journal references are embedded in the text.
Students using these during lecture strongly prefer this.
And because the site is constantly being updated,
numbered endnotes would be unmanageable.
What's available online, and for whom, is always changing.
Most public libraries will be happy to help you get an article
that you need. Good luck on your own searches, and again,
if there is any way in which I can help you, please contact me at
scalpel_blade@yahoo.com.
No texting or chat messages, please. Ordinary e-mails are welcome.
Health and friendship!
The porphyrias are a family of diseases caused by errors of heme synthesis,
variably expressed and
(no doubt) much under-diagnosed (Postgrad. Med. 86: 295, 1989). Since porphyrin
synthesis enzymes are in short supply, the common ones are autosomal
dominants. All porphyrias are semi-treatable. All get missed, and the patients suffer and die (Medicine 71: 1, 1992).
Easy updates: Lancet 365: 241, 2005; Ann. Int. Med. 142: 439, 2005;
Am. J. Clin. Path. 119(S3): S-86, 2003; Lancet 375: 924, 2010;
Blood 120: 4496, 2012.
These people have fragile skin in any case, and biopsying isn't a good idea.
People with these porphyrias complain of severe pain beginning
a few minutes after ultraviolet light exposure.
The idea is that
since certain chemicals in large quantities can give anybody porphyria
with vague mental and physical complaints, then certain people must have
similar complaints because they are
super-sensitive to many other chemicals.
* When hemochromatosis is the problem, the severity of the
porphyria for the amount of iron depends some on the allele: Lancet 349: 1025, 1997; Blood 95: 1565, 2000.
Puzzle that one out. for the very iron-overloaded: Arch. Derm.
139: 309, 2003 -- anyway, wouldn't you rather have twice-a-week
phlebotomy than take medication?
The classic histopathology is a thick deposition of PAS-positive
material around the blood vessels in the upper dermis. Again, no one really
understands this. (You can see this in PCT, and you can see PCT-like blisters
in protoporphyria. But again, you shouldn't have biopsied in the first place.)
* Eventually you may have enough increase in porphobilinogen (or whatever
causes the neuropathy of porphyria) to produce a neuropathy: Neurology 51: 262, 1998.
Erythrodontia (red teeth)
Mayo Clinic
Fluorescent teeth
Mayo Clinic
The worst was "Turkish porphyria" (1954-1959).
Seed grain treated with hexachlorobenzene ended up getting
eaten instead. Worst-affected were children of nursing mothers; all died.
Follow-up: Arch. Neuro. 39: 744, 1982.
Henry's Clinical Diagnosis and Management by Laboratory Methods
Robbins and Cotran Pathologic Basis of Disease
Rosai and Ackerman's Surgical Pathology
Rubin's Pathology: Clinicopathologic Foundations of Medicine
Demay's Cytopathology
New visitors to www.pathguy.com reset Jan. 30, 2005: |
Ed says, "This world would be a sorry place if
people like me who call ourselves Christians
didn't try to act as good as
other
good people
."
Prayer Request
Teaching Pathology
If you have a
Second Life
account, please visit my teammates and me at the
Medical Examiner's office.
PathMax -- Shawn E. Cowper MD's
pathology education links
Ed's Autopsy Page
Notes for Good Lecturers
Small Group Teaching
Socratic
Teaching
Preventing "F"'s
Classroom Control
"I Hate Histology!"
Ed's Physiology Challenge
Pathology Identification
Keys ("Kansas City Field Guide to Pathology")
Ed's Basic Science
Trivia Quiz -- have a chuckle!
Rudolf
Virchow on Pathology Education -- humor
Curriculum Position Paper -- humor
The Pathology Blues
Ed's Pathology Review for USMLE I
Pathological Chess |
Taser Video 83.4 MB 7:26 min |
Click here to
see the author prove you can have fun skydiving without being world-class. Click here to see the author's friend, Dr. Ken Savage, do it right. |