The Anemias:
- Iron-deficiency anemia
- Megaloblastic anemia/Pernicious Anemia
- Aplastic anemia
- Fanconi anemia
- Thalassemia major
- Thalassemia minor
- Polycythemia vera
- Hereditary hemachromatosis
- Hereditary ovalocytosis
- Hereditary spherocytosis
- Hypochromic anemia
- Hemolytic anemia
- Hemolytic disease of the newborn
- Microangiopathic hemolytic anemia
- Hemoglobin CC disease
- Hemoglobin SS disease (sickle cell)
Iron-Deficiency Anemia
Iron-deficiency anemia is one of the most common types of anemias, particularly in the United States of America. This type of anemia can be caused by either:
1) A lower level of red blood cells than normal (the body is not producing enough), and/or
2) Lower levels of hemoglobin.
Maintaining iron balance largely occurs by the absorption of dietary iron. The normal daily Western diet contains about 10-20 mg of iron. This typically comes from heme, available in animal products, and some from vegetables. About 20% of heme is absorbable. Iron-deficiency is due to a number of things and can be caused by insufficient dietary intake of iron, defective iron absorption mechanisms, various types of cancer, or blood loss leading to loss of hemoglobin and iron. This can be due to trauma, heavy menstrual cycles, intestinal bleeding (cancers, polyps, ulcers, colitis, Crohn's disease, bacterial or parasite infection, etc...), uterine bleeding (pregnancy, cancers, fibroids, miscarriage, menstrual cycle, post-partum bleeding, etc...), or even the urinary tract (infection, kidney or bladder stones, cancers, etc...), or diseases that interfere with iron absorption (gluten intolerance, Celiac Disease, inflammatory bowel disease, ulcerative colitis, Tropical Sprue, Sprue, etc...). In this case, the body cannot keep up the pace with the level of replacement of RBCs as they are lost. Infants are at higher risk for iron-deficiency anemia since milk diets don't contain high levels of iron. Children are at risk since they need an increase in dietary iron to support growth and development.
Because free iron is very toxic, the pool of stored iron is tightly bound to ferritin or hemosiderin. Ferritin is a rich protein-iron complex found in all tissues, especially in the liver, spleen, bone marrow, and muscles. In the liver, most of the ferritin is stored in the parenchymal cells. In the spleen and bone marrow, on the other hand, it is mainly found in the phagocytic cells. The iron in hemosiderin is very chemically reactive so it will turn blue-black when exposed to potassium ferrocyanide, part of the Prussian blue stain. With normal iron stores, simply a trace of hemosiderin will be found in the body. In iron-overloaded cells, most iron is stored in hemosiderin. Trace amounts of ferritin normally circulate in the plasma. Serum ferritin is <12 ug/L in iron deficiency. In iron-overload, it is up to 5000 ug/L. Serum levels of transferrin are around 120 ug/L in men and 100 ug/L in women.
Signs and symptoms of advanced iron-deficiency (anemia) include the following:
1) A lower level of red blood cells than normal (the body is not producing enough), and/or
2) Lower levels of hemoglobin.
Maintaining iron balance largely occurs by the absorption of dietary iron. The normal daily Western diet contains about 10-20 mg of iron. This typically comes from heme, available in animal products, and some from vegetables. About 20% of heme is absorbable. Iron-deficiency is due to a number of things and can be caused by insufficient dietary intake of iron, defective iron absorption mechanisms, various types of cancer, or blood loss leading to loss of hemoglobin and iron. This can be due to trauma, heavy menstrual cycles, intestinal bleeding (cancers, polyps, ulcers, colitis, Crohn's disease, bacterial or parasite infection, etc...), uterine bleeding (pregnancy, cancers, fibroids, miscarriage, menstrual cycle, post-partum bleeding, etc...), or even the urinary tract (infection, kidney or bladder stones, cancers, etc...), or diseases that interfere with iron absorption (gluten intolerance, Celiac Disease, inflammatory bowel disease, ulcerative colitis, Tropical Sprue, Sprue, etc...). In this case, the body cannot keep up the pace with the level of replacement of RBCs as they are lost. Infants are at higher risk for iron-deficiency anemia since milk diets don't contain high levels of iron. Children are at risk since they need an increase in dietary iron to support growth and development.
Because free iron is very toxic, the pool of stored iron is tightly bound to ferritin or hemosiderin. Ferritin is a rich protein-iron complex found in all tissues, especially in the liver, spleen, bone marrow, and muscles. In the liver, most of the ferritin is stored in the parenchymal cells. In the spleen and bone marrow, on the other hand, it is mainly found in the phagocytic cells. The iron in hemosiderin is very chemically reactive so it will turn blue-black when exposed to potassium ferrocyanide, part of the Prussian blue stain. With normal iron stores, simply a trace of hemosiderin will be found in the body. In iron-overloaded cells, most iron is stored in hemosiderin. Trace amounts of ferritin normally circulate in the plasma. Serum ferritin is <12 ug/L in iron deficiency. In iron-overload, it is up to 5000 ug/L. Serum levels of transferrin are around 120 ug/L in men and 100 ug/L in women.
Signs and symptoms of advanced iron-deficiency (anemia) include the following:
- Hypochromic, microcytic anemia (RBC's are pale in the middle, smaller, spherocytes)
- Poikilocytosis (RBC's lose their normal discoid shape and become irregular)
- Polychromasia (bluish color to immature RBC's being produced by the bone marrow)
- Decreased hemoglobin values (Hgb)
- Decreased hematocrit (Hct)
- Decreased serum iron and ferritin
- Total plasma iron-binding capacity is high
- Reduction of transferrin saturation
- Possible positive occult blood test (stool) if colorectal cancer is present or there is a bleeding ulcer somewhere
The red blood cells of iron-deficiency anemia are HYPOCHROMIC, meaning that they lack red pigment due to loss of hemoglobin and iron. The RBCs also display POIKILOCYTOSIS and ANISOCYTOSIS, a variety of shapes and sizes respectively.By E. Uthman, MD - http://www.flickr.com/photos/euthman/2274260085/, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=5463883
Poikilocytosis and Anisocytosis, RBCs that are a variety of shapes (stomatocytes, ovalocytes, dacrocytes, some reticulocytes) and sizes (some microcytes and macrocytes) and they are a sign of anemia.By Dr Graham Beards - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20525151
Hypochromic RBCs with a larger area of central pallor mean a lack of hemoglobin, iron and oxygen, resulting in weakness, pallor, fatigue, confusion, dizziness, and other symptomsBy Ed Uthman from Houston, TX, USA - Iron-deficiency Anemia, Peripheral Blood SmearUploaded by CFCF, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=30104241
Megaloblastic/Pernicious Anemia:
Facts About Vitamin B12 (Cobalamin):
Megaloblastic anemia, also called pernicious anemia, is a type of anemia that is caused by a deficiency of vitamin B12 (cobalamin) or folic acid, chemotherapy, autoimmune disease, gluten intolerance, or some antimicrobials. Blood smears may reveal hypersegmented neutrophils (>5 lobes) and/or megaloblasts, which are large, immature, dysfunctional red blood cells.
Vitamin B12 (cobalamin) and folate (folic acid) are coenzymes that are required for the synthesis of thymidine, which is one of the four bases found in DNA (thymine). A deficiency in any of these vitamins or a problem in their metabolism will result in defective nuclear maturity or inadequate DNA synthesis. This slows down or completely blocks cell division. This results in the abnormality of the red blood cell shape and neutrophil shape. These morphologic features are referred to as pancytopenia. The variation in the size and shape of the red blood cells is referred to as anisocytosis. Many red cells are macrocytic (larger) and oval (ovalocytes), with the mean corpuscular cell volumes increasing to >100 fl. The MCHC is not elevated, however, the reticulocyte count may be low. Neutrophils appear larger than normal with 5-6 nuclear lobes.
Vitamin B12 is nearly totally reliant on dietary animal products. Microbes are the origin of cobalamin on the food chain. Plants and vegetables do not contain much, therefore, vegans may suffer from pernicious anemia. The daily need is 2-3 mg. Absorption of the complex requires intrinsic factor. Intrinsic factor is secreted by the parietal cells of the fundic mucosa of the stomach, and is needed for the absorption of vitamin B12 and folic acid by the small intestine. In 1-2% of cases of this type of autoimmune vitamin deficiency, parietal cells are destroyed, which secrete intrinsic factor into the fundic mucosa.
Vitamin B12 and folic acid/folate deficiency may be caused by a number of conditions, including:
Signs and Symptoms:
Diagnostic Features:
Elevated Levels of Vitamin B12:
- It is water-soluble
- It plays a role in myelin synthesis, which covers nerves in the nervous system
- It plays a role in proper nervous system functioning
- It plays a role in the maturation of red blood cells from the bone marrow
- It plays a role in cellular metabolism in each and every cell
- It is a cofactor in DNA synthesis
- We cannot synthesize (make) it and so it must be obtained from the diet
- It is one of 8 B vitamins
- It is the largest and most complex vitamin
- It contains the element cobalt
Megaloblastic anemia, also called pernicious anemia, is a type of anemia that is caused by a deficiency of vitamin B12 (cobalamin) or folic acid, chemotherapy, autoimmune disease, gluten intolerance, or some antimicrobials. Blood smears may reveal hypersegmented neutrophils (>5 lobes) and/or megaloblasts, which are large, immature, dysfunctional red blood cells.
Vitamin B12 (cobalamin) and folate (folic acid) are coenzymes that are required for the synthesis of thymidine, which is one of the four bases found in DNA (thymine). A deficiency in any of these vitamins or a problem in their metabolism will result in defective nuclear maturity or inadequate DNA synthesis. This slows down or completely blocks cell division. This results in the abnormality of the red blood cell shape and neutrophil shape. These morphologic features are referred to as pancytopenia. The variation in the size and shape of the red blood cells is referred to as anisocytosis. Many red cells are macrocytic (larger) and oval (ovalocytes), with the mean corpuscular cell volumes increasing to >100 fl. The MCHC is not elevated, however, the reticulocyte count may be low. Neutrophils appear larger than normal with 5-6 nuclear lobes.
Vitamin B12 is nearly totally reliant on dietary animal products. Microbes are the origin of cobalamin on the food chain. Plants and vegetables do not contain much, therefore, vegans may suffer from pernicious anemia. The daily need is 2-3 mg. Absorption of the complex requires intrinsic factor. Intrinsic factor is secreted by the parietal cells of the fundic mucosa of the stomach, and is needed for the absorption of vitamin B12 and folic acid by the small intestine. In 1-2% of cases of this type of autoimmune vitamin deficiency, parietal cells are destroyed, which secrete intrinsic factor into the fundic mucosa.
Vitamin B12 and folic acid/folate deficiency may be caused by a number of conditions, including:
- malabsorption conditions
- atrophic gastritis
- dietery deficiency (insufficient intake) over a period of years
- deficient intrinsic factor (found in the microvilli of the intestines, so conditions that damage the microvilli will result in this and can be autoimmune, viral, bacterial, due to a parasite infection, allergies such as to gluten, etc...)
- tapeworm infestation, particularly fish tapeworm
- gastrectomy
- Celiac disease
- diverticulitis
- intestinal surgeries such as ileal resection or ileitis
- pancreatitis
- alcoholism
- pregnancy
- enzyme deficiencies
- bacterial overgrowth in blind loops
- diverticula of bowel
- administration of some types of therapeutic drugs
- toxic drugs (some types of chemotherapy)
- oral contraceptives
- anticonvulsants
- hemodialysis
- folic acid antagonist
- metabolic inhibitor to DNA synthesis or folate metabolism, such as methotrexate
- nitrous oxide (anesthesia) reactions
- erythroleukemia
- hyperthyroidism
- disseminated cancer
- lymphoma
- chronic infections
- genetic predisposition (tendency to form antibodies against multiple self-antigens)
- autoimmune destruction of gastric mucosa (chronic atrophic gastritis with loss of parietal cells)
- Type I antibody that blocks binding of vitamin B12 to intrinsic factor (found in plasma and gastric juice)
- Type II antibody prevents binding of intrinsic factor-vitamin B12 complex to its ideal receptor
- Type III antibody is formed most likely as a result from gastric injury
- An auto reactive T-cell response initiative gastric mucosal injury, which in turn triggers the formation of autoantibodies
Signs and Symptoms:
- Glossitis (tongue is shiny, glazed, "beefy")
- Gastritis
- Neurological symptoms such as dizziness, forgetfulness, loss of balance, dementia, mania, psychosis, lethargy, depression, brain shrinkage, shaking, nervousness, anxiety, moodiness, spasms, sensory ataxia, paraparesis, paresthesias, numbness, tingling, degenerative changes in the basal ganglia, sensory and motor pathways cause muscle and nervous system problems, restless leg syndrome, fatigue, lack of motivation, low energy, weakness, changes in eyesight, such as blurry vision, decreased night vision, muscles not functioning properly as the optic nerve may become compromised due to lack of the vitamin complex
- Can cause permanent and irreversible effects
Diagnostic Features:
- Megaloblastic anemia
- Macrocytosis (larger RBC's, target cells)
- Leukopenia (decreased WBC's)
- Hypersegmented granulocytes (neutrophils with >5 lobes)
- Mild to moderate thrombocytopenia (low platelets)
- Mild jaundice
- Possible hemolysis of red blood cells
- Low serum levels of vitamin B12
- Elevated levels of homocysteine and methyl masonic acid in the serum (risk factor for atherosclerosis and thrombosis and vascular disease)
- Serum antibodies to intrinsic factor
Elevated Levels of Vitamin B12:
- Can be a marker/sign of serious disease
- liver disease
- acute hepatitis
- cirrhosis
- hepatocellular carcinoma
- metastatic liver disease
- CML (leukemia)
- Promyelocytic leukemia
- polycythemia vera
- hypereosinophilic syndrome
- smoking
- alcoholism
Aplastic Anemia
Aplastic anemia is a disease of the bone marrow in which the stem cells are damaged and fail to produce new mature cells. In fact, bone marrow biopsies will tend to show very few stem cells, which have mostly been replaced with fat. This type of anemia can actually be fatal. It results in pancytopenia (a deficiency of ALL THREE cell lines, RBCs, WBCs and platelets). Exposure to toxic drugs, radiation, chemotherapy, infections, autoimmune disease, viruses (Epstein-Barr, Cytomegalovirus, Hepatitis, Parvovirus B19, HIV) are all conditions that can cause this type of anemia. A stem cell transplant is required to treat this type of anemia.
Signs and Symptoms:
Signs and Symptoms:
- Fatigue
- Shortness of Breath
- Chronic nosebleeds, gum bleeds, prolonged bleeding from cuts
- Pale skin
- Rapid or irregular heartbeat
- Frequent, prolonged infections
- Easy bruising
- Rash
- Dizziness
- Headaches
Fanconi Anemia
Fanconi anemia is an inherited anemia that can result in bone marrow failure or cancer. Not only is it a blood disease, but it can also affect all the other organs of the body, and can be fatal. It results in an impaired response to DNA damage. It is extremely rare, and when it occurs, it often results in cancer (AML) and bone marrow failure in about 90% of individuals who have it. Most individuals with this type of anemia suffer from other side effects, including congenital defects, short stature, physical abnormalities, and learning disabilities. Bone marrow transplant is the only type of long-term treatment, but the average lifespan is still just 30 years of age.
Diamond-Blackfan Anemia
Diamond-blackfan anemia is also an inherited type of anemia resulting in pure red blood cell aplasia. This type of anemia results in low red blood cell count, but does not affect the other two cell lines as Fanconi anemia does.
THE THALASSEMIAS:
The thalassemias are types of anemia characterized by low hemoglobin production. Symptoms range from none to severe depending on the type of thalassemia involved. They are genetic and inherited from one's parents. There are two major types: 1) Alpha Thalassemia, 2) Beta Thalassemia. Both are inherited in an autosomal-recessive manner.
Signs and symptoms typically include the following:
Signs and symptoms typically include the following:
- Mild-to-severe anemia with a low red blood cell count
- Feeling tired, fatigued, pale skin, bone problems, enlarged spleen and liver, jaundice, dark urine, growth stunted in children, increased susceptibility to infection, heart problems
- Iron-overloading (hemosiderosis)
- Microcytosis (smaller RBC's), target cells
- Genetic testing shows deletion of the 16p chromosome or problems with the HBA1 or HBA2 gene (missing or deleted), with decreased alpha-globin production, with excess of B-chains in adults and excess y-chains in newborns OR mutations in the HBB gene on chromosome 11
Thalassemia Major/Alpha Thalassemia
- Very serious, severe anemia that begins prior to birth
- Genetic
- Unable to make enough hemoglobin
- Excess beta globulins
- Shortened RBC lifespan than the normal 120 day lifespan
- RBC's become fragile and break
Thalassemia Minor/Beta Thalassemia
- Cooley's Anemia
- Symptoms begin within the first 2 years of life
- Excess alpha globulins lead to anemia and ineffective erythropoiesis
Polycythemia vera/Increased RBCs, Many of Them Abnormal
- Hematocrit is >55%
- Increased number of red blood cells
- May be due to a decrease in plasma volume
- Also called erythrocytosis
- May be caused by a primary problem with the bone marrow (myeloproliferative disorder), malignancy, a response to low oxygen, high altitude, malignancy, or blood doping
- Primary polycythemia
- Polycythemia vera
- Polycythemia rubra vera
- Abnormality of the bone marrow (excess platelets and WBCs may also be produced)
- Symptoms include headaches, dizziness, enlarged liver and/or spleen, possible high blood pressure, possible blood clots
- >55% hematocrit
- Only treatment is therapeutic phlebotomy to remove some of the blood
- Often genetic/hereditary and due to a mutation
- Secondary polycythemia
- Altitude sickness
- Cyanosis/Hypoxia (Sleep Apnea, COPD, Heart Disease)
- Induced by Phlebotomy
- Genetic
- Neoplasms
- Receiving some sort of hormone therapy
- Anabolic steroids
By The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 404905. Image and description are from the AFIP Atlas of Tumor Pathology.Declaration of PEIR: «Copyright Information - The Armed Forces Institute of Pathology Electronic Fascicles (CD-ROM Version of the Atlas of Tumor Pathology) contains both U.S. Government work and copyrighted materials used with permission of non-Government contributors. U.S. Government works may be used without restriction, but users of the Electronic Fascicle may not lawfully modify, rent, loan, distribute, create derivative works in whole or in part, or electronically transmit the copyrighted images from one computer to another or over a network without first obtaining permission from the copyright owners. All attempts have been made to remove copyrighted images from the PEIR Digital Library. If a copyright-protected image has inadvertently been included, please notify us and it will be removed immediately.», Public Domain, https://commons.wikimedia.org/w/index.php?curid=4352246
Hereditary Hemochromatosis/Iron-Overloading/Ringed Sideroblasts
Ovalocytosis: Hereditary Elliptocytosis
Hereditary Elliptocytosis
Hereditary Spherocytosis
Sickle Cell Anemia
Hypochromic/Lack of Hemoglobin/Iron-Deficiency Anemia
Hyperchromic/Reticulocytosis/Polychromasia
Hemolytic Anemias:
Associated with the following:
Types of cells you will see, depending on the condition, include:
- Uremia (kidney failure)
- Hemolytic Uremic Syndrome (HUS)
- Severe burns
- Microangiopathic anemia
- Disseminated intravascular coagulation
- Thrombotic thrombocytopenic purpura (TTP)
- Malignant hypertension
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Glucose-6-phosphate-dehydrogenase deficiency
- Hereditary thalassemias
- Sickle cell crisis
Types of cells you will see, depending on the condition, include:
- microcytes
- macrocytes
- polychromasia
- fragmented cells (schistocytes/helmet cells/keratinocytes/triangulocytes)
- teardrop cells (dacrocytes)
- hypochromic cells
- acanthocytes (spur cells)
- echinocytes (burr cells)
- other odd shapes (poikilocytosis/anisocytosis)
Microangiopathic Hemolytic Anemia:
Microangiopathic anemia is represented by fragmented cells damaged by the spleen. Helmet cells (schistocytes), acanthocytes, keratinocytes, echinocytes, macrocytes, microcytes, and polychromic cells can be seen in the image below. There are a handful of causes of this type of anemia, including:
- Pregnancy
- Malignancy
- Systemic lupus crisis
- Hemolytic uremic syndrome
- Renal failure
- Chemotherapy drugs
- Thrombosis (blood clot)
- Trauma
- Transfusion reaction
- Disorders that affect the liver and spleen
Additional Slide Gallery:
Associated Terminology:
Hypoxemia/Hypoxia:
- Hypoxemia is an abnormally low concentration of oxygen in the blood, which is a sign of anemia
- Low arterial oxygen
- Anoxemia is zero arterial oxygen
- Respiratory alkalosis
- Pulmonary embolism
- Diving
- High altitude sickness
- Low arterial oxygen
- Hypoxia is a condition in which the low supply of oxygen is not sufficient for normal life functions, and this is often seen in organ failure and septic shock, including low blood pressure, rapid heart rate, rapid and shallow breathing, shortness of breath, rapid respiration rate, confusion, difficulty communicating or inability to communicate, may lead to coma, may be fatal; Also called cyanosis
- Oxygen is deprived at the tissue level
- Can lead to organ dysfunction and damage
- Pathological most of the time
- Can be normal (temporarily) if someone is training or undergoing strenuous exercise or traveling to higher altitude
- Generalized Altitude Sickness
- Complications: high altitude pulmonary edema, high altitude cerebral edema
- Diving hypoxia
- Preterm birth
- Complications: high altitude pulmonary edema, high altitude cerebral edema
- Localized
- Cyanosis
- Anemia
- Cardiac arrest
- Respiratory problems or diseases
- Sepsis
- Cyanosis
- Generalized Altitude Sickness
- Anoxia is complete oxygen deprivation
- Oxygen is deprived at the tissue level
- Monitored by pulse oximeters, arterial blood gases, or pulmonary function tests
- This is serious and is treated with oxygen, possible intubation, possible hyperbaric chamber therapy, and medications to open up the airways
- There are many causes but a few include:
- Asthma attack
- Drowning
- Carbon monoxide poisoning
- Drug poisoning
- Alcohol poisoning
- Suffocation
- Asphyxiation
- Bacterial sepsis and septic shock
- Stroke
- Myocardial infarction
- COPD
- Smoke exposure
- High mountain climbing and altitude sickness
- Emphysema
- Bronchitis
- Anaphylaxis and allergic reactions
- Pulmonary edema
- Pneumonia
- Sleep apnea
- Pneumothorax
- Lung cancers
- Choking
- Some medications
- Anemia
- Traumatic injuries
- Ischemia
- Lack of blood flow to a tissue, leading to hypoxia (embolism, heart attack, gangrene, peripheral vascular disease)
- Lack of blood flow to a tissue, leading to hypoxia (embolism, heart attack, gangrene, peripheral vascular disease)