Impaired production Flashcards
talk of hypersegmented neutrophil and macro-ovalocytes means what?
Vitamin B12 or Folate deficiency
folate is a cofactor for making
B12
“lots of blue means lots of new…?”
reticulocytes
THe higher the MCV, the more likely it is to be..
B12
How long can you go without B12 vs folate?
B12– years
folate– months, maybe just weeks
what do we treat people with who have a B12 or folate deficiency?
always treat with both, because we can’t tell which one is deficient
pencil cells are classic for
iron deficiency anemia
can be from cancer or iron deficiency
the lower MCV is, the more likely it is to be…
iron deficiency
how saturated is transferrin usually?
1/3
hemosiderin
another storage form of iron, in macrophages
hepcidin
shuts down the ferroportin so no more iron comes in
Anemias of Diminished Erythropoiesis
The most common and important anemias associated with red cell underproduction are those caused by nutritional deficiencies, followed by those that arise secondary to renal failure and chronic inflammation
Also included are less common disorders that lead to generalized bone marrow failure, such as aplastic anemia, primary hematopoietic neoplasms, and infiltrative disorders that lead to marrow replacement (e.g., metastatic cancer and disseminated granulomatous disease)
Megaloblastic Anemias
The common theme among the various causes of megaloblastic anemia is an * impairment of DNA synthesis that leads to ineffective hematopoiesis and distinctive morphologic changes, including abnormally * large erythroid precursors and red cells
Pernicious anemia
is a specific form of megaloblastic anemia caused by an autoimmune gastritis that impairs the production of intrinsic factor, which is required for vitamin B12 uptake from the gut
Autoimmune attack on the gastric mucosa. Histologically, there is a chronic atrophic gastritis
Antibodies in pernicious anemia
About 75% of pernicious anemia patients have a type I antibody that blocks the binding of vitamin B12 to intrinsic factor. Type I antibodies are found in both plasma and gastric juice.
Type II antibodies prevent binding of the intrinsic factor-vitamin B12 complex to its ileal receptor. These antibodies are also found in a large proportion of patients with pernicious anemia.
Type III antibodies are present in 85% to 90% of patients and recognize the α and β subunits of the gastric proton pump, which is normally localized to the microvilli of the canalicular system of the gastric parietal cell.
Diagnostic clinical Features of Pernicious Anemia
Moderate to severe megaloblastic anemia
(2) Leukopenia with hypersegmented granulocytes
(3) Low serum vitamin B12
(4) Elevated serum levels of homocysteine and methylmalonic acid
The diagnosis of pernicious anemia is confirmed by
an outpouring of reticulocytes and a rise in hematocrit levels beginning about 5 days after parenteral administration of vitamin B12. Serum antibodies to intrinsic factor are highly specific for pernicious anemia
Pernicious anemia have an increased risk of
gastric carcinoma.
Elevated homocysteine levels are a risk factor for atherosclerosis and thrombosis, and it is suspected that vitamin B12 deficiency may increase the incidence of vascular disease
Anemia of Folate Deficiency
A deficiency of folic acid (more properly, pteroylmonoglutamic acid) results in a megaloblastic anemia having the * same pathologic features as that caused by vitamin B12 deficiency
- Suppressed synthesis of DNA, the common denominator of folic acid and vitamin B12 deficiency, is the immediate cause of megaloblastosis
The three major causes of folic acid deficiency are
Decreased intake
Increased requirements
Impaired utilization
Polyglutamates are sensitive to heat
boiling, steaming, or frying of foods for 5 to 10 minutes destroys up to 95% of the folate content. Intestinal conjugases split the polyglutamates into monoglutamates that are readily absorbed in the proximal jejunum.*
The body’s reserves of folate are relatively modest, and a deficiency can arise within *weeks to months if intake is inadequate
dietary inadequacies in anemia of folate deficiency
Dietary inadequacies are most frequently encountered in chronic alcoholics, the indigent, and the very old
Malabsorption syndromes, such as sprue, can lead to inadequate absorption of this nutrient, as can diffuse infiltrative diseases of the small intestine (e.g., lymphoma).
In addition, certain drugs, particularly the * anticonvulsant phenytoin and oral contraceptives,* interfere with absorption
relative deficiency - folate
Despite normal intake of folic acid, a relative deficiency can be encountered when requirements are increased.
Conditions in which this is seen include pregnancy, infancy, derangements associated with hyperactive hematopoiesis (hemolytic anemias), and disseminated cancer
drugs and folate deficiency
Folic acid antagonists, such as methotrexate, inhibit dihydrofolate reductase and lead to a deficiency of FH4.
Many chemotherapeutic drugs used in the treatment of cancer damage DNA or inhibit DNA synthesis through other mechanisms; these can also cause megaloblastic changes in rapidly dividing cells
The megaloblastic anemia that results from a deficiency of folic acid is identical to that encountered in
vitamin B12 deficiency. Thus, the diagnosis of folate deficiency can be made only by demonstration of decreased folate levels in the serum or red cells.
homocysteine and folate deficiency
As in vitamin B12 deficiency, serum homocysteine levels are increased, but methylmalonate concentrations are normal. However, neurologic changes do not occur.
what else responds to folate therapy?
Although prompt hematologic response heralded by reticulocytosis follows the administration of folic acid, it should be remembered that the hematologic symptoms of vitamin B12 deficiency anemia also respond to folate therapy.
folate and the vitamin B12 neurologic deficits
folate does not prevent (and may even exacerbate) the neurologic deficits typical of the vitamin B12 deficiency states. It is thus essential to exclude vitamin B12 deficiency in megaloblastic anemia before initiating therapy with folate.
most common nutritional disorder in the world
Deficiency of iron is the most common nutritional disorder in the world and results in a clinical signs and symptoms that are mostly related to inadequate hemoglobin synthesis
Iron versus hepciden
Iron absorption is regulated by hepcidin, a small circulating peptide that is synthesized and released from the liver in response to increases in intrahepatic iron levels
Alterations in hepcidin have a central role in diseases involving disturbances of iron metabolism
The anemia of chronic disease (perhaps more accurately referred to as the anemia of chronic inflammation) is caused in part by inflammatory mediators that increase hepatic hepcidin production.
Conversely, hepcidin activity is inappropriately low in both primary and secondary hemochromatosis, a syndrome caused by systemic iron overload.
Secondary hemochromatosis can occur in diseases associated with ineffective erythropoiesis, such as β-thalassemia major and myelodysplastic syndromes
Iron Deficiency Anemia Causes
Dietary lack
Impaired absorption
Increased requirement
Chronic blood loss
Dietary lack
of iron
Infants, who are at high risk due to the very small amounts of iron in milk. Human breast milk provides only about 0.3 mg/L of iron. Cow’s milk contains about twice as much iron, but its bioavailability is poor.
The impoverished, who can have suboptimal diets for socioeconomic reasons at any age
Older adults, who often have restricted diets with little meat because of limited income or poor dentition
Teenagers who subsist on “junk” food
impaired iron absorption
Sprue, other causes of fat malabsorption (steatorrhea), and chronic diarrhea.
Gastrectomy impairs iron absorption by decreasing the acidity of the proximal duodenum (which enhances uptake), and also by increasing the speed with which gut contents pass through the duodenum.
increased requirement of iron
Growing infants, children, and adolescents, as well as premenopausal women, particularly during pregnancy.
Economically deprived women having multiple, closely spaced pregnancies are at exceptionally high risk
Chronic blood loss
and iron
Chronic blood loss is the most common cause of iron deficiency in the Western world
External hemorrhage or bleeding into the gastrointestinal, urinary, or genital tracts depletes iron reserves.
Iron deficiency in adult men and postmenopausal women in the Western world must be attributed to gastrointestinal blood loss until proven otherwise!
clinical features of iron deficiency
spoon shaped nails
misshapen tongue
The diagnosis of iron deficiency anemia ultimately rests on laboratory studies
Both the hemoglobin and hematocrit are depressed, usually to a moderate degree, in association with hypochromia, microcytosis, and modest poikilocytosis.
The serum iron and ferritin are low, and the total plasma iron-binding capacity (reflecting elevated transferrin levels) is high. Low serum iron with increased iron-binding capacity results in a reduction of transferrin saturation to below 15%
