RED CELLS
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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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.

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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.

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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 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!

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Courtesy of CancerWEB

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Taiwanese pathology site
Good place to go to practice

Blood 1
Smears
Indiana U.

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Photos, explanations, and quiz
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Photomicrograph collection
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Iowa Virtual Microscopy
Have fun

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Brown Digital Pathology
Some nice cases

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Nice photos
UMDNJ

Bloodline
Category index
Great hematology image collection

Hematology Atlas
Nivaldo Medeiros MD
Brazilian Pathologist

American Society of Hematology (?!)
Image Bank
For the gung-ho students


Anemias For Understanders

TOO MANY RED CELLS BEING DESTROYED IN THE BODY (hemolysis)
TOO MANY RED CELLS BEING LOST FROM THE BODY (acute hemorrhage)
ENOUGH HEMOGLOBIN NOT BEING MADE

ENOUGH NORMOBLASTS NOT BEING MADE



All hemolytic disorders:

Spherocytosis: Spherocytes (look smallish as they don't lie flat, no central pallor) on peripheral smear; Increased MCHC (hyperchromasia -- remember spherocytosis as the one genuine cause)

Paroxysmal nocturnal hemoglobinuria: New molecular assays have replaced the old Ham test (acid hemolysis)

Enzyme deficiencies: Heinz bodies

Abnormal hemoglobins: Target cells ("codocytes"; Mexican hat cells; if it's extremely humid or the tech uses a blow-dryer on the slide, you'll get these as artifact)

Sickle cell disease: Sickled cells (drepanocytes; if in doubt, remember sickled red cells have no central pallor)

Hemoglobin C disease (two doses): Hemoglobin C crystals (add a drop of vinegar to see them better; it also helps if the spleen is gone)

Hemoglobin SC disease: Hemoglobin SC ("birds in flight") crystals

Immune hemolysis: Spherocytes (especially true microscopherocytes, because portions of the membrane have been removed); Positive direct Coombs' test. (Savvy labs now give you a free Coombs test if you're found to have unexplained elevated reticulocytes: Am. J. Clin. Path. 124: 129, 2005).

Some mechanical hemolysis (clostridia, burns, prosthetic heart valves, microangiopathy): Schistocytes and other fragments on peripheral smear

Acute hemorrhage: Increased reticulocytes

Enough hemoglobin not being made: Decreased MCV (microcytosis); Decreased MCHC (hypochromia)

Not enough usable iron: Decreased serum iron

Actual iron deficiency (none stored): Very low serum ferritin (reliable); Zero stainable marrow iron stores (but who needs to check?); low serum iron (usually), increased total iron binding capacity / low transferrin saturation (less reliable than serum ferritin).

Free erythrocyte protoporphyrin: Screening tool for iron deficiency, best in kids. Why? (Also picks up lead poisoning. Why?)

Anemia of inflammation / sideroblastic anemias: Increased serum ferritin; total iron binding capacity not indreased

Sideroblastic anemia: Dimorphic population (some forms); Ringed sideroblasts in marrow

Lead poisoning: Coarse basophilic stippling (maybe -- lead inhibits ribonuclease)

Basophilic stippling

WebPath Photo

Thalassemias: Coarse basophilic stippling (maybe); Pancake cells ("leptocytes")

Enough normoblasts not being made: Decreased reticulocytes

Not enough nucleic acid being made: Increased MCV (macrocytosis); Hypersegmented PMN's

B12 deficiency: Low serum B12; Perform a Schilling test (if you can get the isotope)

Classic pernicious anemia: Schilling test becomes normal on addition of extrinsic factor; with the isotope unavailable, just check the blood for antibodies against gastric parietal cell antibodies (maybe 70% sensitive and 50% specific if you're just fishing) and maybe intrinsic factor antibodies (J. Clin. Path. 62: 439, 2009, even less sensitive and rare if anti-parietal cell antibodies are not present); do a good H&P, make a presumptive diagnosis and treat

Folic acid deficiency: Low red cell folate (avoids the pitfall of plasma fluctuations with diet)

Infiltrative disease of bone marrow: Teardrop red cells (it's still unsettled, but your lecturer believes that teardrop red cells are the ones made in spleen)


KCUMB Students
"Big Robbins" -- RBC / Bleeding
Lectures follow Textbook

QUIZBANK

Blood Banking!
WebPath Tutorial

Red cells

WebPath Photo

Coulter counter

WebPath Photo

Normal automated hemogram printout

WebPath Photo

INTRODUCTION

ANEMIAS OVERSIMPLIFIED (see also Lancet 355: 1169 & 1260, 2000)

ANEMIAS OF BLOOD LOSS

HEMOLYTIC ANEMIAS: INTRODUCTION

Howell-Jolly bodies and nucleated red

WebPath Photo

Hemolytic anemia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Thick skull
Juvenile hemolysis
WebPath Photo

HEREDITARY SPHEROCYTOSIS

Spherocytosis

WebPath Photo

Spherocytosis

WebPath Photo

Spherocytosis
Spleen
WebPath Photo

Parvo B-19 hydrops fetalis

Yutaka Tsutsumi MD

Parvovirus B19
Aplastic crisis in hereditary spherocytosis
Yutaka Tsutsumi MD

HEMOLYTIC DISEASE DUE TO ERYTHROCYTE ENZYME DEFECTS

SICKLE CELL DISEASE (Ped. Clin. N.A. 49: 1193, 2002; Lancet 376: 2018, 2010)

Sickle cell disease

WebPath Photo

Sickle cell disease

WebPath Photo

Sickle Cell Anemia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Sickle cell disease
Autosplenectomy
WebPath Photo

HEMOGLOBIN C DISEASE

Hemoglobin C

WebPath Photo

HEMOGLOBIN E DISEASE

THE THALASSEMIAS ("Cooley's anemia", "Mediterranean blood", etc.; Am. Fam. Phys. 80: 339, 2009; Lancet 379: 373, 2012)

Thalassemia Minor
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA ("PNH")

AUTOIMMUNE HEMOLYTIC ANEMIAS

HEMOLYTIC ANEMIA RESULTING FROM TRAUMA TO RED CELLS

Schistocytes

WebPath Photo

DIC
Schistocytes, no platelets
Wikimedia Commons

Burr Cells in Uremia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

MEGALOBLASTIC ANEMIAS

Megaloblastic anemia
Automated printout
WebPath Photo

Hypersegmented poly
Pernicious anemia
KU Collection

Hypersegmented poly
Megaloblastic anemia
WebPath Photo

Megaloblastic anemia

WebPath Photo

IRON DEFICIENCY ANEMIAS

Pathology of Iron Metabolism
WebPath Tutorial

Iron deficiency

WebPath Photo

Iron deficiency

WebPath Photo

Automated printout -- iron deficiency

WebPath Photo

Iron Deficiency Anemia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Iron deficiency anemia
Peripheral smear
KU Collection

ANEMIA OF (CHRONIC) INFLAMMATION ("Anemia of Chronic Disease", NEJM 352: 1011, 2005)

SIDEROBLASTIC ANEMIA

PURE RED CELL APLASIA

Normal marrow
Section
WebPath Photo

Normal marrow
Higher power, section
WebPath Photo

Normal marrow
Smear
WebPath Photo

Normal marrow

WebPath Photo

Normal marrow

WebPath Photo

Rouleaux formation

WebPath Photo

FINISHING UP: Thankfully, hemoglobins with excessively high oxygen affinity ("Chesapeake" and many others) are uncommon. As you'd expect, these render the patient polycythemic.

* Red-cell substitutes have been a disappointment. A bovine hemoglobin preparation delivers the goods but only lasts for a day in the bloodstream; it is now in widespread use in some nations and helps JW's in the USA. The older perfluorocarbon emulsions ("Fluosol", others) required patients to breathe 100% oxygen which was deadly to the lungs. Review Am. J. Clin. Path. 118 S: S-71, 2002. Update from the Hop: Arch. Path. Lab. Med. 131: 734, 2007.

We'll do polycythemia vera, other secondary polycythemias, acquired (autoimmune) aplastic anemia, and the myelodysplastic syndrome under "White Cells". Enjoy these pictures:

{13856} red cell, normal blood. (If platelets stick to polys, it's EDTA anticoagulant effect ("satellitism"). Some folks have a gene to make this happen.)

JEHOVAH'S WITNESSES AND BLOOD TRANSFUSION

{13858} red cell, normal marrow, unusual stain
{13976} red cell, normal blood (two orthochromatic normoblasts)
{20780} red cell, normal blood
{46538} red cell, normal blood
{26161} basophilic normoblast (prorubricyte)
{26162} basophilic normoblast (prorubricyte)
{26197} basophilic normoblast (prorubricyte)
{26198} basophilic normoblast (prorubricyte)
{26223} polychromatophilic normoblast (rubricyte)
{26224} polychromatophilic normoblast (rubricyte)
{18690} orthochromatophilic normoblast (metarubricyte)
{10127}red cell, even staining for hemoglobin

{10130} Heinz bodies
{10418} nucleated red cells in hemolytic disease of the newborn
{21113} hemolytic disease of the newborn
{13898} polychromasia (the purple, large red cells are "reticulocytes")
{14722} reticulocytes, normal
{14723} reticulocytes, too many
{39616} erythroid hyperplasia
{39617} erythroid hyperplasia


{27434} plasmodium vivax
{13880} cold agglutinins in the blood
{12299} hereditary spherocytosis
{16172} spherocytes
{11547} hereditary elliptocytosis (spherocytosis variant)
{13892} hereditary elliptocytosis (spherocytosis variant)
{12305} spur cells ("acanthocytes"' E.T.-finger cells); abetalipoproteinemia case; there are other odd genetic syndromes featuring this anomaly
{13871} abetalipoproteinemia smear (lymphocyte in upper right)
{20128} abetalipoproteinemia smear


{17419} sickle cell disease
{13907} target cells
{16167} target cells
{16177} target cells
{16169} stomatocytes (flattened uniconcave RBC's typical of acute drunkenness, liver disease and various rarities, everyone's allowed a few)
{12308} schistocytes
{13895} schistocyte
{16178} schistocytes
{17137} DIC
{20149} thalassemia
{13877} basophilic stippling
{10430} "megaloblasts" (i.e., the red cell precursors in pernicious anemia)


{13751} megaloblastic blood smear
{13754} megaloblastic marrow
{13757} megaloblastic marrow
{13889} macro-ovalocytes (i.e., megaloblastic anemia)
{12302} teardrops


{14013} sideroblastic blood (dimorphic RBC population)
{27342} ringed sideroblasts, iron stain (not the greatest photo)
{09054} iron in mitochondria
{14025} Pappenheimer body (retained iron-loaded mitochondrion, i.e., you have sideroblastic anemia and/or have had a splenectomy; you need a Prussian blue stain to see them well)
{16168} Pappenheimer bodies
{13854} polycythemia vera blood
{13976} rouleaux
{14028} multinucleated red cell (DiGuglielmo's?)
{23920} myelodysplastic syndrome
{13883} Howell-Jolly bodies (stray chromosomes not extruded; usually mean the patient has had a splenectomy -- say, after trauma, for treatment of bad thalassemia or spherocytosis, or a sickler's autosplenectomy -- and they were not removed)


{16170} Howell-Jolly bodies
{13904} post-splenectomy
{29011} blood bank

Howell-Jolly bodies and nucleated red

WebPath Photo

Let the young sing songs of death. They are stupid. The finest thing under the sun and the moon is the human soul. I marvel at the small miracles of kindness that pass between humans. I marvel at the growth of conscience, at the persistence of reason in the face of all superstition and despair. I marvel at human endurance.

BIBLIOGRAPHY / FURTHER READING

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