Impaired production

Question 1

talk of hypersegmented neutrophil and macro-ovalocytes means what?

Answer 1

Vitamin B12 or Folate deficiency

Question 2

folate is a cofactor for making

Answer 2

B12

Question 3

“lots of blue means lots of new…?”

Answer 3

reticulocytes

Question 4

THe higher the MCV, the more likely it is to be..

Answer 4

B12

Question 5

How long can you go without B12 vs folate?

Answer 5

B12– years

folate– months, maybe just weeks

Question 6

what do we treat people with who have a B12 or folate deficiency?

Answer 6

always treat with both, because we can’t tell which one is deficient

Question 7

pencil cells are classic for

Answer 7

iron deficiency anemia

can be from cancer or iron deficiency

Question 8

the lower MCV is, the more likely it is to be…

Answer 8

iron deficiency

Question 9

how saturated is transferrin usually?

Answer 9

1/3

Question 10

hemosiderin

Answer 10

another storage form of iron, in macrophages

Question 11

hepcidin

Answer 11

shuts down the ferroportin so no more iron comes in

Question 12

Anemias of Diminished Erythropoiesis

Answer 12

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)

Question 13

Megaloblastic Anemias

Answer 13

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

Question 14

Pernicious anemia

Answer 14

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

Question 15

Antibodies in pernicious anemia

Answer 15

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.

Question 16

Diagnostic clinical Features of Pernicious Anemia

Answer 16

Moderate to severe megaloblastic anemia

(2) Leukopenia with hypersegmented granulocytes
(3) Low serum vitamin B12
(4) Elevated serum levels of homocysteine and methylmalonic acid

Question 17

The diagnosis of pernicious anemia is confirmed by

Answer 17

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

Question 18

Pernicious anemia have an increased risk of

Answer 18

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

Question 19

Anemia of Folate Deficiency

Answer 19

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

Question 20

The three major causes of folic acid deficiency are

Answer 20

Decreased intake
Increased requirements
Impaired utilization

Question 21

Polyglutamates are sensitive to heat

Answer 21

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

Question 22

dietary inadequacies in anemia of folate deficiency

Answer 22

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

Question 23

relative deficiency - folate

Answer 23

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

Question 24

drugs and folate deficiency

Answer 24

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

Question 25

The megaloblastic anemia that results from a deficiency of folic acid is identical to that encountered in

Answer 25

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.

Question 26

homocysteine and folate deficiency

Answer 26

As in vitamin B12 deficiency, serum homocysteine levels are increased, but methylmalonate concentrations are normal. However, neurologic changes do not occur.

Question 27

what else responds to folate therapy?

Answer 27

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.

Question 28

folate and the vitamin B12 neurologic deficits

Answer 28

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.

Question 29

most common nutritional disorder in the world

Answer 29

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

Question 30

Iron versus hepciden

Answer 30

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

Question 31

Alterations in hepcidin have a central role in diseases involving disturbances of iron metabolism

Answer 31

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

Question 32

Iron Deficiency Anemia Causes

Answer 32

Dietary lack Impaired absorption Increased requirement Chronic blood loss

Question 33

Dietary lack | of iron

Answer 33

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

Question 34

impaired iron absorption

Answer 34

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.

Question 35

increased requirement of iron

Answer 35

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

Question 36

Chronic blood loss | and iron

Answer 36

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!

Question 37

clinical features of iron deficiency

Answer 37

spoon shaped nails misshapen tongue

Question 38

The diagnosis of iron deficiency anemia ultimately rests on laboratory studies

Answer 38

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%