Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com
Cyberfriends: The help you're looking for is probably here.
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.
DoctorGeorge.com is a larger, full-time service.
There is also a fee site at myphysicians.com,
and another at www.afraidtoask.com.
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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. Someday you may be able to access these pictures directly from this page.
Also:
Medmark Pathology -- massive listing of pathology sites
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
handling about 200 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 which 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 which 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 linked below. 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 which 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 which 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 presently have no sponsor.
This page was last updated February 6, 2006.
During the ten 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 KCUMB 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 KCUMB
for making it 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!
GETTING "SPINAL FLUID"
In caring for patients, you will frequently perform lumbar puncture to obtain spinal fluid for
diagnostic purposes. (Reviews: Ann. Int. Med. 104: 840 & 880, 1986; Am. Fam. Phys. 35(6): 112,
1987).
*You are familiar with the anatomy, physiology, and composition of the CSF from other basic
science courses, especially our excellent neurobiology course. (For a review, see Ann. Neurol. 11:
1, 1982.)
*You will learn the technique of lumbar puncture including the measurement and interpretation of
CSF initial pressure ("opening pressure", normally 50-180 mm CSF, elevated in meningitis,
subarachnoid hemorrhage, tumor, abscess, pseudotumor cerebri, lead encephalopathy) during
rotations. You will also learn the old Quickenstadt test, etc., etc. The tray cost $14 in 1980.
Indications for this procedure include suspected CNS infection (by far the most important),
hemorrhage, or leukemia (indications for emergency LP), suspected primary tumor, demyelinating
disease, Guillain-Barré disease, etc. (indications for elective LP).
*It is good to perform elective LP's first thing in the morning. The patient's blood and CSF glucose
levels will be equilibrated, lab's day-shift will examine the specimen.
*Also remember that most people are terrified of LP's. Reassure your patient before beginning the
procedure.
Relative contraindications to LP include:
*Other hazards of lumbar puncture include:
When you have successfully penetrated the subarachnoid space and have measured the spinal fluid
pressure, you are ready to collect your fluid. One recommended way is to collect 2 cc in each of
four plain tubes:
first tube: to MICROBIOLOGY
(gram stain $10, culture and sensitivity $32, acid-fast stain and culture $40, fungal stain and culture
$24, India ink for cryptococcus $10, bacterial antigens $50, virus culture $200)
second tube: to CHEMISTRY
(glucose $8, protein $10, serum protein electrophoresis $53)
third tube: to HEMATOLOGY
("CBC" and differential count $23)
fourth tube: to SEROLOGY and/or ANATOMIC PATHOLOGY
(syphilis test $11, cancer cytology $40, etc., etc.)
The rationale behind this order for collecting your samples is this:
Tissue elements introduced into the CSF by needle trauma (skin, ligament, blood, etc.) will end up
in the fluid sent to Microbiology, where they will cause the least confusion.
Blood in the CSF from a "traumatic tap" is generally easy to spot in the manometer, as it is not
uniformly mixed with the clear fluid. Following a "traumatic tap", there will be appreciably more
blood in the first tube than in later tubes.
(If you are still concerned that the blood in the CSF may be due to a subarachnoid hemorrhage,
remember that this will produce xanthochromia in all but the most acute situations. See below.)
*Another little-known source of confusion is the frequent presence of bone marrow elements in the
first tube. This can simulate "CML involving the meninges". See NEJM 308: 697, 1983.
Of course, what you order depends on the clinical context.
RULE: If the opening pressure, cell count, and protein are normal, and the patient is an adult in
whom you do not suspect immunosuppression or multiple sclerosis, then any additional tests are
very unlikely to yield useful information (Lancet 1: 1 & 769, 1987; Ann. Int. Med. 104: 840,
1986).
"SPINAL FLUID" APPEARANCE
CSF is normally clear as distilled water. * The best way to look at the CSF is straight down through
the top of the test tube (JAMA 253: 2496, 1985) or using a bright x-ray viewing light (JAMA 253:
39, 1985).
Turbid CSF indicates the presence of 200-400 or more cells/cu mcL (normal less than 5, see below).
*Turbidity is rated 0-4+, depending on whether one can see and read newsprint through the tube.
The commonest and most worrisome color change seen in CSF is xanthochromia, the result of red
blood cells undergoing hemolysis in the CSF.
This ranges from pink (a few hours after the bleed, from free hemoglobin) to yellow (a day or more
after the bleed, from bilirubin).
*Red cells probably lyse in the CSF because their membrane integrity depends on their being
surrounded by a certain concentration of serum proteins.
*Newborns and preemies are likely to have yellowish CSF because their immature blood-brain
barrier allows bilirubin to enter it.
*Other causes of yellowish CSF include melanin (metastatic melanoma), carotene (carrot addicts),
the iodine used to cleanse the skin over the puncture site (sloppy puncturist), and rifampin (Ann.
Neurol. 12: 228, 1982). Very high protein levels can also give a pale yellow tinge.
It is very important to note whether the tap has been traumatic. This can and does conceal
meningitis (Clin. Ped. 25: 523 & 575, 1987).
"SPINAL FLUID" CHEMISTRIES
CSF protein normally is around 40-90 mg/dL.
Values will of course be higher in inflammatory processes, cancers, etc., involving the meninges or
ventricles.
*Correction factors exist in case you have a bloody tap. Remember the protein content of plasma is
around 1 times that of serum.
CSF glucose is normally around half of whatever the serum value was an hour or two previously.
(In fasting patients with normal serum glucose, the normal range is around 40-70 mg/dL.)
Low CSF glucose suggests bacterial, TB, fungal, or amebic meningitis, or (less often) meningeal
involvement by cancer.
It is usual to send a serum glucose to the lab at the same time as the CSF.
"SPINAL FLUID" CELLS
CSF ordinarily contains only a few cells (0-5/cu mcL). These are lymphocytes, pia-arachnoid cells,
and a few monocytes.
*If your tap is bloody, you can calculate the expected white cell count using this formula:
The factor .2 is empirical and poorly understood. See J. Pediatr. 107: 249, 1985.
Increased neutrophils suggests bacterial meningitis.
*It may also be seen in early viral meningitis, and in TB, fungal, or syphilitic meningitis, in amebic
infection, or in "aseptic meningitis" due to an abscess or other septic focus below the meninges.
*It may also be seen in acute CNS hemorrhage, acute infarct, or metastatic cancer. (Note that the
same things cause polys to enter the CSF as cause them to migrate anywhere else.)
Even a single poly in a non-traumatic tap is very worrisome, though up to 3 cells/mcL might be
normal (Pediatrics 75: 484, 1985; Am. Fam. Phys. 36(4): 58, 1987).
Increased lymphocytes suggests viral meningitis.
*It may also be seen in resolving bacterial meningitis, in TB, fungal, syphilitic, or parasitic
meningitis, in "aseptic meningitis" (as above), in demyelinating and autoimmune diseases.
* Macrophages in the CSF suggest TB or fungal meningitis, or may be present following hemorrhage
into the subarachnoid space (look for siderophages after the first week....)
* Plasma cells may be present where there is abnormal immunoglobulin production in the CNS
(multiple sclerosis, SSPE, lupus, tuberculosis, fungus infections).
* Eosinophils may be present in small numbers and are not very informative.
Tumor cells (carcinoma cells, leukemic blasts) are detectable in CSF in somewhat fewer than half of
cases with meningeal involvement. * Future cytopathologists see Acta Cytol. 29: 286, 1985, and
Clin. Lab. Med. 5: 275, 1985.
OTHER TESTS
CSF protein electrophoresis: analogous to serum protein electrophoresis in principle.
A simultaneous serum protein electrophoresis is usually performed. (Other techniques, especially
isoelectric focusing, are replacing electrophoresis.)
A few distinct monoclonal-type spikes ("oligoclonal bands") in the gamma region of the CSF
(without any corresponding bands on serum protein electrophoresis) are supposed to help make the
diagnosis of multiple sclerosis and will usually be present in clinically obvious cases. See Clin.
Chem. 29: 810, 1983, and Acta. Neurol. Scand. 67: 365, 1983.
Immunoglobulin production in the CSF can be estimated using various formulas. One example:
(CSF IgG/plasma IgG)/(CSF albumin/plasma albumin)
This is generally increased in "immune" disease of the CNS (including active multiple sclerosis,
SSPE, and lupus cerebritis). But it is not really specific and is likely to elevated in any CNS
infection, acute stroke, and even Alzheimer's disease.
*The old Pandy phenol and colloidal gold tests for CSF proteins are obsolete.
Myelin basic protein: a reference lab procedure. The test is typically positive during acute
demyelinating episodes of multiple sclerosis, and even patients with quiescent disease usually have
mile elevations. (It may also be positive in SSPE, Guillain-Barré syndrome, radiation damage, CNS
lupus, after a CVA, etc. See Acta Neurol. Scand. 67: 365, 1983.)
* Spinal fluid CEA: quite specific for intracranial cancer.
* Spinal fluid beta-2-microglobulin: currently experimental test to detect primary or metastatic
cancer involving the meninges.
Bacterial meningitis antigens: indicated if you at all suspect....
Sensitive counterimmunoelectrophoresis (older) and/or latex agglutination (newer) procedures are
extensively used to detect soluble antigens from pathogenic microorganisms.
The lab will probably test for pneumococcus, various meningococci, H. 'flu, and (for babies) strep B.
Results will be available in minutes to a few hours.
Antibiotics won't spoil this test, though they may make it impossible to culture the responsible
organism.
India ink preparation for Cryptococcus. Probably indicated in any case of suspected meningitis,
though the sensitivity is only around 50%.
Syphilis serology and viral serologies
Fungal serologies
The latex agglutination procedure for detecting cryptococcal antigen is extremely sensitive and
specific (false positives in severe rheumatoid arthritis: why?) and is indicated whenever you
encounter meningitis (nowadays, anybody can have AIDS....)
Many other serologic tests are available for other diseases.
* CSF FINDINGS IN SPECIFIC DISEASES. Don't expect all to be present in
all cases.
Bacterial meningitis
CSF clear to purulent
increased initial pressure
increased protein
decreased glucose
increased polys (often more than 1000/mcL)
increased lymphs (some, typically after treatment)
positive gram stain, culture, and/or meningitis antigens
Brain abscess
CSF usually clear
increased initial pressure
increased protein
normal glucose
increased cells ("aseptic meningitis", seldom over 100/mcL)
Leptospiral meningitis
Like other bacterial meningitis, with a mix of polys and lymphs
Neurosyphilis
may see increased protein, mild lymphocytosis, and/or plasma cells
positive blood FTA-ABS
positive CSF VDRL
Tuberculous meningitis
CSF clear to cloudy
increased initial pressure
increased protein
decreased glucose
increased polys and/or lymphs (not over 1000/mcL)
positive AFB's
Cryptococcal meningitis
CSF usually clear, may be viscous (gooey capsular substance)
increased protein
decreased glucose
increased cells (seldom over 1000/mcL, mostly lymphs)
positive India Ink
positive cryptococcal latex agglutination
Viral meningitis
CSF clear to cloudy
increased initial pressure
increased protein
normal glucose
increased cells (not over 1000/mcL, polys on day 1, then more lymphs)
a specific virus is incriminated by rising titer after patient is better
Multiple sclerosis and SSPE
may be entirely normal, especially between acute episodes of MS
increased globulin
oligoclonal bands
mild lymphocytosis and plasmacytosis
increased IgG synthesis (usually)
increased myelin basic protein (usually)
For reviews of lymphocyte subsets in various stages of MS, see Ann. N.Y. Acad. Sci. 436: 151,
1984, and J. Clin. Invest. 74: 1307, 1984.
The old "anti-myelin antibodies" test is probably worthless.
Guillain-Barré syndrome
only abnormalities are mildly increased protein, minimal (if any) lymphocytosis
Brain tumor
CSF usually clear unless there has been bleeding
increased initial pressure
increased protein
normal glucose (may be low)
increased cells
cancer cells
Pseudotumor cerebri
increased initial pressure without other abnormalities
Subarachnoid hemorrhage
CSF bloody, is usually xanthochromic within a few hours
increased initial pressure (usually)
increased protein
increased polys (reactive, later)
Intracerebral hemorrhage
Same as subarachnoid hemorrhage, except that blood may not reach the subarachnoid space in a
minority of cases
Alzheimer's disease, "functional headache", lumbar disc disease, etc., etc.
No abnormalities.
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Houston Pathology -- loads of great pictures for student doctors
Pathopic -- Swiss site; great resource for the truly hard-core
Syracuse -- pathology cases
Walter Reed -- surgical cases
Alabama's Interactive Pathology Lab
"Companion to Big Robbins" -- very little here yet
Alberta
Pathology Images --hard-core!
Cornell
Image Collection -- great site
Bristol Biomedical
Image Archive
EMBBS Clinical
Photo Library
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
Iowa Skin
Pathology
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
National Museum of Health & Medicine -- Armed Forces Institute of Pathology
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
WebPath:
Internet Pathology
Laboratory -- great site
My team:Ed Lulo's Pathology Gallery
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Dan Hammoudi's Site
Claude Roofian's Site
Pathology Handout -- Korean student-generated site; I am pleased to permit their use of my cartoons
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 which may work well for you
We comply with the
HONcode standard for health trust worthy
information:
verify
here. 
CSF WBC=.2 x CSF RBC x (Blood WBC / Blood RBC)
| 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
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 |
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Taser Video 83.4 MB 7:26 min |
