Macrocytosis Flashcards
explain microcyte, macrocyte, and the role of mean corpuscular volume (MCV) in assessing red blood cell size
Normal RBC (Red Blood Cell) Size: Typically falls within the range of 80-100 femtoliters (fL) when measured using MCV. This is considered the normal size for red blood cells.
Microcyte: Refers to red blood cells that are smaller than the normal range, typically below 80 fL. Microcytosis can be indicative of conditions such as iron-deficiency anemia or thalassemia.
Macrocyte: Indicates red blood cells that are larger than the normal range, typically above 100 fL. Macrocytosis can result from a reduction in the number of smaller cells, an excess of larger cells, or underlying medical conditions such as vitamin B12 deficiency or folate deficiency.
Mean corpuscular volume (MCV) is a valuable parameter in the complete blood count (CBC) that helps evaluate the average size of red blood cells. Deviations from the normal MCV range can provide important diagnostic information and guide further clinical assessments in cases of anemia and other blood disorders.
explain the stages of erythropoiesis
15-20 µm - Basophilic Cytoplasm, Nucleus with Nucleoli:
Early erythroid precursors exhibit a relatively large cell size, basophilic (blue) cytoplasm, and a nucleus with visible nucleoli.
14-17 µm - Mitosis, Basophilic Cytoplasm, Nucleoli Disappears:
As erythroid precursors progress, they may undergo mitosis. Nucleoli disappear, and the basophilic cytoplasm persists.
10-15 µm - Polychromasia, Hb Appears, Nucleus Condenses:
At this stage, erythroid precursors become smaller (10-15 µm) and exhibit polychromasia, indicating the presence of hemoglobin (Hb). The nucleus condenses.
7-10 µm - Pyknotic Nucleus, Extrusion, Hb is Maximum:
The cells continue to shrink, and the nucleus undergoes pyknotic changes, eventually extruding from the cell. Hemoglobin content is at its maximum.
7.3 µm - Reticulum of Basophilic Material in the Cytoplasm:
At this stage, a reticulum of basophilic (blue) material is observed in the cytoplasm. This represents the synthesis and organization of hemoglobin.
7.2 µm - Mature Red Cell with Hb:
The final stage results in a mature red blood cell (erythrocyte) with a diameter of approximately 7.2 µm. It has a condensed, non-functional nucleus and is filled with hemoglobin.
give an overview of anemia and the classification of anemia based on mean corpuscular volume (MCV)
Anemia: Anemia is a condition characterized by a reduced number of red blood cells or a decrease in the amount of hemoglobin in the blood, resulting in reduced oxygen-carrying capacity.
Microcytic Anemia (< 80fL): Microcytic anemia is characterized by small red blood cells, typically with an MCV of less than 80 femtoliters (fL). This category includes various types of anemia, such as:
Thalassemia
Iron-deficiency anemia
Anemia of chronic disease
Sideroblastic anemia
Macrocytic Anemia (> 100fL): Macrocytic anemia is characterized by large red blood cells, typically with an MCV of greater than 100 fL. This can be associated with conditions like vitamin B12 deficiency or folate deficiency.
Normocytic Anemia (80 - 100fL): Normocytic anemia refers to a condition where the size of red blood cells falls within the normal range, typically having an MCV of 80 to 100 fL.
explain the difference between megaloblastic and non-megaloblastic anemias based on the status of DNA synthesis
Megaloblastic Anemia:
In megaloblastic anemia, DNA synthesis has been inhibited or impaired.
This inhibition is typically due to deficiencies in essential nutrients such as vitamin B12 or folate.
The impaired DNA synthesis results in the abnormal maturation of red blood cell precursors, leading to the production of large and immature red blood cells called megaloblasts.
Non-Megaloblastic Anemia:
In non-megaloblastic anemias, DNA synthesis has not been inhibited.
Non-megaloblastic anemias can have various underlying causes, including iron-deficiency anemia, chronic diseases, hemolytic anemias, and others.
The red blood cells in non-megaloblastic anemias may not exhibit the characteristic large size and immaturity seen in megaloblastic anemias.
explain the classification of anemia based on mean corpuscular volume (MCV) and the presence or absence of megaloblastic features
Microcytic Anemia (< 80fL):
This category includes anemia with smaller red blood cells. Potential causes include: Thalassemia, Iron-deficiency anemia, Anemia of chronic disease, Sideroblastic anemia
Macrocytic Anemia (> 100fL):
Macrocytic anemia is characterized by larger red blood cells. Causes can be megaloblastic, with hypersegmented nuclei, and may include: Vitamin B12 deficiency, Folate deficiency, Myelodysplasia (a group of disorders that affect the bone marrow), Medications
Non-Megaloblastic Anemia:
Non-megaloblastic macrocytic anemia can have various underlying causes and does not exhibit the characteristic hypersegmented nuclei seen in megaloblastic anemia. Potential causes include: Alcohol consumption, Hereditary spherocytosis (a genetic disorder affecting red blood cells), Hypothyroidism (underactive thyroid), Hemolysis (destruction of red blood cells)
Normocytic Anemia (80 - 100fL):
Normocytic anemia encompasses anemia with red blood cells of normal size (MCV between 80 and 100fL).
explain the most common causes of macrocytosis
Alcoholism: Chronic alcohol consumption can lead to macrocytosis due to its adverse effects on vitamin absorption, particularly folate. Alcohol can also directly affect the bone marrow.
B12 Deficiency: Vitamin B12 deficiency can result in macrocytosis. B12 is essential for DNA synthesis and red blood cell maturation. A lack of B12 can lead to megaloblastic anemia, characterized by larger and immature red blood cells.
Folate Deficiency: Folate deficiency, often caused by B12 deficiency, can lead to macrocytosis. Folate is also crucial for DNA synthesis, and its deficiency can result in megaloblastic anemia.
Side Effects of Medicines: Some medications, particularly those that affect DNA synthesis or bone marrow function, can lead to macrocytosis. These may include certain chemotherapy drugs and antiretroviral medications.
Hypothyroidism: Underactive thyroid (hypothyroidism) can be associated with macrocytosis. Thyroid hormones play a role in red blood cell production, and thyroid dysfunction can impact this process.
Myelodysplastic Syndrome: Myelodysplastic syndromes are a group of bone marrow disorders characterized by abnormal blood cell production. Some forms of myelodysplastic syndrome can result in macrocytosis.
explain the most common causes of vitamin B12 deficiency
Pernicious Anemia: Pernicious anemia is an autoimmune condition in which the body’s immune system attacks the stomach’s parietal cells, reducing their ability to produce intrinsic factor. Intrinsic factor is necessary for B12 absorption in the ileum of the small intestine.
Gastrectomy: Surgical removal of all or part of the stomach (gastrectomy) can result in reduced production of intrinsic factor, leading to impaired B12 absorption.
Vegetarian Diet: Vitamin B12 is primarily found in animal products. Individuals following a strict vegetarian or vegan diet may be at risk of B12 deficiency if they do not obtain this nutrient from fortified foods or supplements.
High Use of Antacids/PPI: Long-term use of proton pump inhibitors (PPIs) and antacids can reduce stomach acid production, potentially affecting the release of intrinsic factor and B12 absorption.
Insufficient Pancreatic Enzymes: Conditions that affect the pancreas, such as chronic pancreatitis, can interfere with the digestion and absorption of nutrients, including B12.
Tapeworm Infection: Certain parasitic infections, like tapeworms, can interfere with B12 absorption by consuming or competing for the available B12 in the digestive tract.
Defects in Ileal Mucosa: Conditions that damage the lining of the ileum, the site of B12 absorption, can lead to B12 deficiency. This can include inflammatory bowel diseases or surgical resection of the ileum.
explain the process of vitamin B12 absorption in the body
Digestion: Vitamin B12 is naturally present in animal-based foods. During digestion, stomach acid and digestive enzymes help release B12 from these foods.
Intrinsic Factor (IF): Intrinsic factor is a protein produced by the parietal cells of the stomach. It plays a critical role in B12 absorption. IF is necessary for the efficient absorption of B12 in the small intestine.
B12-IF Complex: In the stomach, IF binds to the B12 molecule, forming a B12-IF complex. This complex protects the B12 from being broken down in the acidic environment of the stomach.
Travel to the Ileum: The B12-IF complex travels to the ileum, which is the final section of the small intestine.
Absorption: In the ileum, the B12-IF complex is recognized by specific receptors on the surface of ileal cells. B12 is then absorbed through these receptors and into the bloodstream, where it can be transported to various cells and tissues in the body.
Vitamin B12 is essential for the production of red blood cells and for the proper functioning of nerve cells, including those in the brain. Without intrinsic factor, only a small amount of B12 can be absorbed, which can lead to B12 deficiency and associated health issues. This is why conditions that affect the production or function of intrinsic factor, such as pernicious anemia, can result in B12 deficiency and the need for B12 supplementation.
explain the different types of antibodies associated with pernicious anemia
Type 1 Intrinsic Factor (IF) Antibody: Type 1 IF antibodies interfere with the binding of vitamin B12 to intrinsic factor (IF). This disruption prevents the formation of the B12-IF complex, which is essential for efficient B12 absorption.
Type 2 Intrinsic Factor (IF) Antibody: Type 2 IF antibodies hinder the B12-IF complex from connecting to the ileum, the site of B12 absorption in the small intestine. This action disrupts the final step of B12 uptake, reducing the amount of B12 that can enter the bloodstream.
Parietal Cell Antibodies: Parietal cell antibodies target the parietal cells in the stomach. Parietal cells are responsible for producing stomach acid and intrinsic factor. When these antibodies attack parietal cells, it can lead to a reduction in both stomach acid and IF production, further impairing B12 absorption.
explain pernicious anaemia
Onset in Adulthood: Pernicious anemia is typically seen in adults and is less common in younger individuals. Symptoms are usually not apparent until after the age of 30, with the average age of diagnosis around 60.
Autoimmune Condition: Pernicious anemia is an autoimmune disorder in which the immune system targets specific components, primarily intrinsic factor. This immune response results in the failure of intrinsic factor, a crucial factor for vitamin B12 absorption.
Prevalence: The prevalence of pernicious anemia is estimated to be around 4% in elderly North Europeans and Africans but is relatively rare in Asians. This could be due to genetic and environmental factors that influence susceptibility.
Impaired RBC Development: Pernicious anemia leads to poor development of red blood cells (RBCs), resulting in a type of macrocytic anemia. Many immature RBCs may not mature and remain in the bone marrow.
Historical Significance: Pernicious anemia was first described by Dr. Thomas Addison, and until the early 1920s, it was often fatal within a few years of diagnosis due to the lack of effective treatment options.
Congenital Form: There is also an inherited form of pernicious anemia, which is autosomal recessive and is typically diagnosed in children. This congenital form is known as “Congenital pernicious anemia” and is usually identified before the age of 5.
what full blood count (FBC) do you predict for someone with pernicious anemia?
Hemoglobin (Hb): Reduced hemoglobin levels are a hallmark of anemia. In pernicious anemia, Hb levels are often significantly lower than the reference range. The extent of anemia can vary from mild to severe.
Mean Corpuscular Volume (MCV): MCV measures the size of red blood cells. In pernicious anemia, the MCV is typically elevated, indicating macrocytic anemia. The red blood cells are larger than normal.
B12 Level: Individuals with pernicious anemia will have decreased levels of vitamin B12 in their blood. This is a key diagnostic marker for the condition.
Folate Level: In some cases, pernicious anemia can lead to reduced folate levels as well. Therefore, it’s essential to assess folate levels to understand the full picture of the anemia.
Haematocrit: The hematocrit, which represents the percentage of blood volume occupied by red blood cells, is usually reduced in pernicious anemia due to the lower red blood cell count.
Reticulocyte Count: In pernicious anemia, the reticulocyte count may be decreased. This indicates a decreased production of red blood cells in the bone marrow.
Iron Studies: Iron studies, including serum iron, ferritin, and total iron-binding capacity (TIBC), may be normal or elevated in pernicious anemia, even though the anemia is primarily caused by a B12 deficiency. This is because the body retains iron but cannot use it effectively in the absence of B12.
explain what happens in the early stages of pernicious anemia
Gastrointestinal Symptoms:
Diarrhea
Constipation
Incontinence
Digestive Issues:
Nausea and/or vomiting
Heartburn
Fatigue and Weakness:
Fatigue or lethargy
Light-headedness when standing or with exertion
Appetite and Weight Changes:
Loss of appetite
Skin and Mucous Membrane Changes:
Pale skin or mild jaundice (yellowing of the skin or eyes due to elevated bilirubin)
Beefy red tongue or glossitis (inflammation of the tongue)
Bleeding gums
Cardiovascular Symptoms:
Shortness of breath on exertion (SOBOE)
Skin Pigmentation:
Blotchy skin pigmentation, which can be associated with hyperpigmentation (darkening) or hypopigmentation (lightening) of the skin
explain what happens in the late stages of pernicious anemia when there is nervous system damage due to a deficiency of vitamin B12 (cobalamin)
Confusion: Individuals may experience difficulty thinking clearly and may have cognitive impairment.
Short-Term Memory Loss: Memory problems, particularly affecting short-term memory, can occur.
Depression: Pernicious anemia can contribute to or exacerbate symptoms of depression.
Loss of Balance: Problems with balance and coordination, along with a sensation of unsteadiness, can be experienced.
Parathesia: Paresthesia refers to abnormal sensations, such as tingling or numbness, often felt in the extremities (hands and feet). This is a common neurological symptom in B12 deficiency.
Problems Concentrating/Irritability: Difficulty focusing, irritability, and mood changes are common.
Hallucinations: In severe cases, individuals may experience hallucinations, which are perceptual disturbances involving seeing or hearing things that are not actually present.
Delusions: Delusions are false beliefs that individuals firmly hold, even when presented with evidence to the contrary.
Optic Nerve Atrophy: Optic nerve atrophy can lead to visual disturbances and impairments in vision.
explain jaundice and the yellowing associated with pernicious anemia
Jaundice (Icterus): Jaundice is a yellowish discoloration of the skin, eyes, and mucous membranes caused by the buildup of bilirubin in the bloodstream. It can manifest as a yellowish color, and the shade of yellow can vary from pale yellow to a deeper yellow or even orange. The specific coloration of jaundice can depend on the level of bilirubin and the underlying cause of the condition.
Lemon Color in Pernicious Anemia: In pernicious anemia, the yellowish or lemon coloration of the skin is often referred to as “lemon-yellow” or “lemon color.” This is a specific term used to describe the pale yellowish skin tone that can be associated with the condition. It’s a result of the anemia and pallor that occurs in pernicious anemia, often in conjunction with other symptoms like fatigue, weakness, and neurological complications.
Both jaundice and the lemon color seen in pernicious anemia are clinical signs of underlying health issues, but they can have different contributing factors and appearances. If you or someone you know is experiencing unusual skin color changes or symptoms related to these conditions, it’s important to seek medical evaluation and diagnosis from a healthcare professional to determine the underlying cause and appropriate treatment.
