Macrocytic Anemia

How are vitamin B12 deficiencies treated?

-B12 Intramuscular injection -Nasal spray, patch, pills/capsules

What are the symptoms of CNS demyelinating?

-Irritability, depression, confusion, dementia -Psychosis or schizophrenia

What are the motor symptoms of peripheral demylinating neuropathies?

-Weakness / atrophy / reflexes -Sudomotor: reduced sweat (heat intolerance)

What are causes of macrocytosis?

Alcoholism, vitamin deficiency, or disease of the liver, spleen, or lung

What tissues are affected by the deficiency of tetrahydrofoliate?

Blood, skin, GI tract

How is megaloblastic anemia treated?

Chemotherapy, radiation therapy, etc.

What vitamin deficiencies are most commonly associated with anemia?

Cobalamin (vitamin B12) Foliate (vitamin B9) Pyridoxine (vitamin B6)

What are alternative names for vitamin B12?

Cyanocobalamin and cobalamin

What conditions occur when there is not enough methionine to methylate fatty acids to make myelin?

Demyelinating neuropathy

What is myelophthisic anemia?

Destruction of bone marrow precursor cells

What is the role of glutathione?

Detoxifies free radicals

What groups are commonly affected by vitamin B12 deficiency?

Elderly, alcoholics, and some ova-lacto vegetarians

What is macrocytosis?

Enlarged erythrocytes but no or minimal anemia

T or F? Vitamin B6 deficiency is common in the US, but not in other countries.

False, it is not common in the US, but common in other countries

What is sideroblastic anemia?

Heme synthesis disorder

In macrocytic anemia, Hb is low, and MCV is _______.

High

What are some clinical markers of B12 and foliate deficiencies?

Homocysteine and methylmalonic acid

What is aplastic anemia?

Hypoproliferative bone marrow

What is the cause of megaloblastic anemia?

Inadequate supply of nucleic acids

What type of anemia is most commonly associated with macrocytic anemia?

Megaloblastic anemia

What conditions require a high intake of foliate?

Pregnancy and lactation

What protein is required to absorb vitamin B12 in the mouth and stomach?

R proteins

Why are pancreatic enzymes required to absorb vitamin B12?

Release B12 from R proteins

What organs are most affected by macrocytic anemia?

Skin and GI tract

Where is vitamin B12 absorbed?

Terminal ileum

What about the structure makes cobalt an essential trace mineral?

The co core corrin-ring

T or F? B6 can help treat macrocytic anemia, even if it's not the cause.

True

T or F? Vitamin B12 deficiency is delayed for several years because the liver stores several years' supply.

True

What are some rare causes of vitamin deficiency anemia?

Vitamin B2 (riboflavin), B3 (niacin), choline

Can vitamin deficiencies be genetic?

Yes, genetic metabolic pathway defects can cause vitamin deficiencies

High levels of free radicals can cause _________, a vascular disease responsible for heart attack and stroke.

atherosclerosis

Cystine is needed to make ________.

glutathione

What is megaloblastic anemia?

Macrocytic anemia due to disorders of DNA replication

Why are ova-lacto vegetarians vulnerable to vitamin B12 deficiency?

Milk, cheese, and eggs are important sources of B12 and most veggies are low in B12

Repeated exposure to ______ may contribute to B12 or foliate deficiency.

Nitrous oxide

T or F? Foliate depletes vitamin B12.

True

T or F? Iron, Foliate & B12 deficiencies often coexist in elderly and patients with poor nutrition

True

T or F? Most macrocytic anemia is caused by deficiency in vitamins.

True

T or F? Single exposure to nitrous oxide can cause rapid neuropsychiatric deterioration, parestheisia or ataxia in existing B12 deficiency

True

In macrocytosis, Hb is normal, and MCV is _______.

high

Pyridoxine helps convert _______ to cysteine.

homocysteine

Anemia from B12 malabsorption is called __________.

pernicious anemia

What are some vascular diseases associated with chronic B12/foliate deficiencies?

-Atherosclerosis -Venous thrombosis

What are some derma symptoms of foliate/B12 deficiency?

-Atrophic glossitis Smooth tongue, reduced papillae -Hyperpigmentation -Cheilitis, stomatitis

What are some tests for foliate/B12 deficiencies?

-Blood smear / Blood measures -Direct measures: Serum B12 Erythrocyte Foliate -Metabolite measures: Increased Homocysteine: B12 or Foliate deficiency Increased MMA: B12 deficiency

How do macrocytic conditions differ from megaloblastic anemia?

-Cells are hypochromic -Multi-segmented neutrophils are absent -Unresponsive to B12 or Foliate

What are the causes of macrocytosis?

-Chronic Obstructive Pulmonary Disease (COPD) CO2 retention increases cell water due to increased bicarbonate -Liver disorders High cholesterol and phospholipids increase membrane area Codocytes (Target cells) -Hypothyroidism 10% incidence of megaloblastic anemia Macrocytic anemia unresponsive to B12 or Foliate

What are the characteristics of megaloblastic anemia?

-Erythroblasts grow but don't make enough DNA to divide -Fewer and larger cells -Deficiencies of vitamin B12 or foliate for DNA synthesis

How are foliate deficiencies treated?

-Foliate capsules of tablets -Diet of dark green veggies, citrus fruits, and fortified bread and cereal

What are the symptoms of other B12 deficiency disorders?

-Higher cervical, breast and lung cancer incidence -restless leg, sleep disorders -fractures -hypercholesterolemia

What DNA replication disorders cause megaloblastic anemia?

-Hyper-segmented neutrophils are pathognomonic -Ovalocytes

What are the causes of macrocytosis in accelerated erythropoiesis?

-Increased reticulocytes -Less mature but larger cells -RDW & MCV will be increased -Blood smear shows increased reticulocytes

What are the sensory symptoms of peripheral demylinating neuropathies?

-Paresthesia (burning feet, mouth, tongue, etc.) -Reduced touch sensation -Reduced special senses -Loss or coordination / abnormal gait

What are some neurological disorders associated with chronic foliate/B12 deficiency?

-Peripheral demyelinating neuropathies -CNS demyelinating symptoms

What are some sources of vitamin B12?

-Plants: variable -Meat: high -Most comes from microorganisms

What are the main deficiency causes?

-Pregnancy -Alcoholics -Malnutrition -Certain drugs

What are the symptoms of venous thrombosis?

-Rapid onset regional edema -Tissue infarction

What factors increase erythropoiesis?

-Recovery for hemorrhage or hemolysis -High altitude

What are some causes of B12 malabsorption?

-Reduced oral secretions due to xerostomia and drugs -Reduced gastric secretions due to anti-secretory therapy, gastritis, gastoectomy, etc. -Reduced pancreatic secretion due to pancreatic failure -Intestinal bacterial or parasitic affection -Alimentary disease or surgery -Hereditary disorders in absorption

What are the symptoms of atherosclerosis?

-Stroke -Myocardial Infarction -Peripheral artery disease

What are B12 and foliate needed for?

-Tetrahydrofoliate for DNA synthesis -Methionine to methylate fatty acids to make myelin -Methionine to make cysteine to make glutathione -Degradation of homocysteine and methylmalonic acid

What are B12 and foliate needed for?

1. Make pyridine nucleotides for DNA synthesis 2. Make methionine a. methylate fatty acids to make myelin for neurons b. to make cysteine for glutathione to detoxify free radicals 3. Make glutathione

What conditions cause high cell division?

Anemia, exfoliative dermatitis, cancer, etc.

What vitamins are needed in addition to pyridoxine to convert homocysteine to cysteine?

B12 and B9

What are the symptoms of other foliate deficiency disorders?

Birth (neural tube) defects Pregnancy complications Higher colon cancer incidence

How are macrocytic bone marrow disorders diagnosed?

Bone marrow biopsy

What are the likely causes of other macrocytic conditions?

Certain genetic conditions Alcoholism Splenectomy Liver or lung disease (next slide) Hypothyroidism (next slide) Accelerated erythropoiesis (second slide)

What is a symptom of other B12/foliate deficiency disorders?

Diarrhea from malabsorption due to failure to replace mucosal absorptive cells

Where does most foliate absorption occur?

Duodenum and early jejunum

Why are alcoholics vulnerable to vitamin B12 deficiency?

Glutathione is used up in hepatic alcohol detoxification and alcohol calories displace nutrition-bearing foods

What conditions occur when there is not enough methionine to make cysteine to make glutathione?

Increases oxidative damage

What is myelodyplastic anemia?

Ineffective RBC production causing dysplastic cells

What factor is required to absorb vitamin B12 in the stomach?

Intrinsic factor (most important GI secretion)

Why are B12 and foliate the most common deficiencies?

It is difficult for the body to absorb