WEEK 1: ANAEMIA Flashcards
What is anemia?
*Inadequate capacity of the blood to transport oxygen in the conditions prevailing
*Anemia is a condition marked by a decrease in the number of red blood cells (RBC), the proportion of hemoglobin, or the collective volume of packed RBCs (hematocrit).
Outline and describe the measures of anemia
- Hematocrit or packed cell volume ( Hct or PCV)
It is the measure of the total volume of blood occupied by cells. It is measured in percentage (%)
*Total hemoglobin (Hb) : it is the total hemoglobin content of blood expressed as g/L or g/ dL
*Mean cell volume (MCV) : it is average size of erythrocytes measured in fl ( Femto litres or L x10^-15)
- Mean cell hemoglobin: It is the average amount of hemoglobin per cell in pg ( picogram or g x10^-12)
*Red blood cell count (RBC): the number of red blood cells per liter of blood
State the 2 basic causes of anaemia
- Normal lifespan of erythrocytes but problem with the synthesis process
- Normal synthesis process of erythrocytes but short lifespan of erythrocytes in the body due to early breakdown or abnormal blood loss
State the components of erythrocytes
*Hemoglobin
* cytoskeletal proteins
* Enzymes: carbonic anhydrase and glycolytic enzymes
State other hormones that indirectly influence erythropoiesis
- Androgens: Stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells.
*Growth Hormone:
- Estrogen: Estrogen has been shown to inhibit the production of erythropoietin-stimulating factor (ESF), which is a precursor of erythropoietin (EPO) that requires activation by a kidney mechanism for elaboration of the functional circulating ESF.
*Thyroxine
Why do males have more Hematocrit in blood than women?
*Estrogen inhibits erythropoiesis in females hence less erythrocytes produced
State the requirements for erythropoiesis
Adequate supply of:
* Amino acids
*Iron
*Vitamin B12
*Folic acid
*Other vitamins
Outline factors that may limit hemoglobin synthesis
- lack of iron ( FE2+)
- Error in globin synthesis: Genetic mutation, deficiency essential in amino acids and protein deficiency, Malnutrition
*Error in hem synthesis: Genetic or heavy metal poisoning
Which structure in the life cycle of erythrocyte synthesize hemoglobin?
Pro-erythroblasts
Describe macrocytic anemia
*High MCV and MCH
* MCV greater than 100fl
*DNA synthesis is impaired but hemoglobin synthesis is normal
* Caused by deficiency in vitamin B12 and folate which are needed to convert RNA base uracil to the DNA base thymine
* In this deficiency, RNA synthesis and protein synthesis are normal but DNA synthesis is reduced , so cell division is impaired
Outline possible causes of macrocytic anemia
*cytotoxic drugs
*immuno-suppressants
*anti-HIV therapy
*cancer chemotherapy
Name the 2 types of macrocytic anemia
*megaloblastic (hypersegmented neutrophils)
*non-megaloblastic
Differentiate between megaloblastic and non-megaloblastic macrocytic anemia
M: consists of large immature erythrocytes
NM: consist of large mature erythrocytes
N: Due to vitamin B12 or folate deficiency and drug toxicity
NM: due to alcohol abuse, pregnancy and hypothyroidism
Describe the etiology of macrocytic anaemia
*Megaloblastic anemia occurs from deficiencies in folic acid and vitamin B12.
*Folate deficiency is due to diminished intake (alcohol abuse or malnutrition), increased consumption (hemolysis or pregnancy), malabsorption (familial, gastric bypass, or medications like cholestyramine or metformin).
*Vitamin B12 deficiency appears in diminished intake (malnutrition), malabsorptive states (atrophic gastritis either autoimmune or non-autoimmune from Helicobacter pylori or Zollinger-Ellison syndrome, Diphyllobothrium tapeworm infection, gastric bypass, ileal resection), or the presence of antagonists (nitrous oxide).
*Drugs that impair DNA synthesis are folic acid analogs (ex. methotrexate, trimethoprim-sulfamethoxazole), nucleic acid analogs (5-fluorouracil, zidovudine), and others (hydroxyurea, pentamidine, phenytoin, pyrimethamine, sulfasalazine, triamterene).
Non-megaloblastic anemia, the absence of hyper segmented neutrophils, occurs in a variety of settings.
*Benign conditions are alcohol consumption (RBC toxicity), hereditary spherocytosis (impaired volume regulation increases red cell size), hypothyroidism and liver disease (due to lipid deposition in the cell membrane), and marked reticulocytosis from states of excess RBC consumption such as hemolysis or turnover in pregnancy or primary bone marrow disease (reticulocytes are larger than the average RBCs)
*Some cases of macrocytosis are normal variants associated with a genetic predisposition or found in infants, patients with Down syndrome, and pregnant women.
*Others are spurious findings include hyperglycemia concentrates the blood, and when diluted, the RBCs swell with volume, leukocytosis and paraproteinemia increase sample turbidity for overestimates of RBC size, or operator error from occlusion of microscope aperture or sample left out at room temperature too long
Describe the histopathology of macrocytic anaemia
Macrocytic anemia that is megaloblastic contains hypersegmented neutrophils and macro-ovalocytes on peripheral blood smear (PBS) (figure “macrocytic anemia”). Anisocytosis and poikilocytosis are not uncommon due to ineffective erythropoiesis.
*Bone marrow evaluation will demonstrate hypercellularity with abnormal maturation and proliferation of myeloid cell lines, particularly the erythroid lineage.
Nonmegaloblastic macrocytic anemia will not have hyper segmented neutrophils; instead, its PBS will show round macrocytes or macro reticulocytes, in addition to other cells representative of the underlying etiology (acanthocytes from liver disease, myeloid dysplasia or immaturity in primary bone marrow disease, polychromatophilic RBCs with reticulocytosis, schistocytes from hemolysis, or spherocytes in inherited hemolytic anemias such as hereditary spherocytosis).
Describe the pathophysiology of macrocytic anaemia
The equation for mean corpuscular volume [MCV (fL) = Hct (%) X 10 / RBC (106/microgram)] explains how macrocytic anemia represents large red blood cells (RBCs) in comparison to total amount.
*Folate and vitamin B12 are necessary for RBC nucleic acid synthesis.
*Without DNA or RNA, erythropoiesis is ineffective with nuclear/cytoplasmic asynchrony, resulting in larger erythrogenic precursors with abnormal nuclei (ex. hypersegmentation) but normal cytoplasms.
*Anemia occurring in the presence of macrocytosis and hypersegmented neutrophils is known as megaloblastic anemia.
*The absence of hypersegmented neutrophils characterizes non-megaloblastic anemia.
*This occurs from mechanisms discussed earlier: abnormalities involving the RBC membrane, excess erythrocytic precursors, increased cell volume, or RBC toxicity.
How do healthcare providers diagnose macrocytic anemia?
*Complete blood count (CBC):
Healthcare providers use this test to evaluate your red blood cell count and function.
*Peripheral blood smear (PBS):
This test is a technique healthcare providers use to examine your blood cells. Unlike some blood tests that are analyzed by a machine, healthcare providers analyze your blood cells by looking at them under a microscope.
*Reticulocyte count:
A reticulocyte count measures the number of immature red blood cells (reticulocytes) in your bone marrow. Healthcare providers measure reticulocytes to determine if your bone marrow is producing enough healthy red blood cells.
Describe the characteristics of microcytic anaemia
*Normal cell division but impaired hemoglobin synthesis
*Normal number of cells but a much reduced amount of hemoglobin is produced to fill them
* REDUCED MCV AND MCH
* MCV less than 80fl
* RBC is normal
* Hct and Hb will be reduced
Describe the etiology of microcytic anaemia
*Iron deficiency: This may be due to decreased iron in the diet, poor absorption of iron from the gut, acute and chronic blood loss, increased demand for iron in certain situations like pregnancy or recovering from major trauma or surgery.
*Thalassemia: mutation which inactivates a globin gene synthesis or genes
*Chronic inflammatory disease
* Failure to produce haem component of hemoglobin , which is porphyrin : genetic mutation, lead poisoning ( sideroblastic anaemia)
Describe histopathology of microcytic anaemia
The decreased quantity of hemoglobin in the RBCs leads to a compromised size of RBCs.
*Normal RBCs contain a central zone of pallor, which is usually one-third of the size of RBC; however, in hypochromic microcytic anemia, that size increases, and hemoglobin is usually only present in the peripheral rim of the RBCs.
*The normal size of RBC is about 80 to 100 femtolitre/RBC (fl/RBC); however, in iron deficiency anemia, this size decreases below 80 fl/RBC.
*Normal bone marrow stored iron gives a black-blue color on reaction with Prussian blue dye but, in iron deficiency-related hypochromic microcytic anemia, that stainable iron is markedly decreased or even absent in severe cases. Poikilocytes in the form of small, elongated red cells (pencil cells) are also characteristically seen.
Describe pathophysiology of microcytic anaemia
.
Hypochromic microcytic anemia is caused by any factor which reduces the body’s iron stores. Hemoglobin is a globular protein that is a major component of RBCs it is manufactured in the bone marrow by erythroid progenitor cells. It has four globin chains two of which are alpha-globin chains while the other two are beta-globin chains, these four chains are attached to a porphyrin ring (heme) the center of which contains iron in the form of ferrous (reduced iron) capable of binding four molecules of oxygen. Reduced iron stores halt the production of hemoglobin chains, and its concentration begins to decrease in the newly formed RBCs since the red color of RBCs is due to hemoglobin the color of the newly formed RBCs begins to fade thus the name, hypochromic. As the newly produced RBCs contain less amount of hemoglobin, they are of relatively small size when compared to normal RBCs, thus the name, microcytic.
Iron deficiency hypochromic microcytic anemia is caused due to disruption of iron supply in diet due to decreased iron content in the diet, pathology of the small intestines like sprue and chronic diarrhea, gastrectomy, and deficiency of vitamin C in the diet. It may be due to acute or chronic blood loss and also due to suddenly increased demands of pregnancy or major trauma and surgery.
Reduced hemoglobin in the RBCs decreases the amount of oxygen delivered to the peripheral tissues leading to tissue hypoxia.
Name the protein that transport iron in blood
transferrin protein carries this iron in the blood
Name the iron transporter
Where is iron absorbed?
Iron is subsequently absorbed from the duodenum and upper parts of the jejunum through an iron transporter called ( ferroportin)
What controls the process of iron absorption from the gut?
It is controlled by hepcidin, a protein that regulates the amount of iron absorbed from the diet
*Hepcidin is the main modulator of iron metabolism, giving it a key role in the pathophysiology of anemia of chronic disease.
*An acute-phase protein, the up regulation of hepcidin is facilitated by interleukin-6 (IL-6) and other proinflammatory cytokines.
*Hepcidin binds to the iron export protein, ferroportin, which is present in macrophages, hepatocytes, and enterocytes.
Increased hepcidin levels lead to iron trapping within macrophages and hepatocytes, resulting in low levels of circulating iron. Through negative feedback stimulated by increased iron stores, hepcidin causes enterocytes and macrophages to degrade ferroportin, thus reducing absorption and promoting storage, respectively.
