Iron Overload and Megaloblastic Anemia: White

Question 1

What effects can unbound iron have on tissues?

Answer 1

(1) lipid peroxidation
(2) Fibrosis
(3) Carcinogenesis

Question 2

What is the effect of alcohol on iron?

Answer 2

(1) 30% of chronic alcoholics have iron overload

(2) Folate deficiency increases iron absorption

Question 3

What are the clinical findings of anemia due to alcoholism?

Answer 3

(1) Skin pigmentation
(2) hypogonadism
(3) glucose intolerance
(4) Iron in Kupffer cells.

Question 4

Why does thalassemia lead to iron overload?

Answer 4

Abnormal red blood cells have decreased survival time and are degraded at an increased rate leading to iron accumulation.

Question 5

What clinical problems are associated with thalassemia iron overload?

Answer 5

(1) 1st decade hepatomegaly
(2) lack of sexual development
(3) 2nd decade Cardiomegaly

Question 6

What is hemochromotosis?

Answer 6

Hemochromatosis is a disorder that results in iron overload caused by an autosomal recessive mutation in the HFE gene. (variable penetrance)

Question 7

What is the result of HFE mutation?

Answer 7

A mutation in HFE results in low hepcidin. Low hepcidin causes the accumulation of iron over time. Constant abosrption

Question 8

What is the result of iron overload in various tissues?

Answer 8

(1) Brain: lethargy and confusion
(2) Skin: Hyperpigmentation
(3) Heart: Cardiomyopathy
(4) Liver: cirrhosis and hepatoma
(5) Pancreas: diabetes
(6) Genitals: hypogonadism
(7) Joints: chondrocalcinosis and arthritis.

Question 9

What are the clinical symptoms of hemachromatosis?

Answer 9

(1) Liver function abnormalites 75%
(2) weakness and lethargy 74%
(3) hyperpigmentation 70%
(4) Diabetes 48%
(5) Arthralgias 44%
(6) Impotence in men 45%
(7) EKG changes 31%

Question 10

What are the unusual laboratory findings in hemochromatosis?

Answer 10

(1) Serum iron in excess of 180dl
(2) TIBC normal to low
(3) % saturation > 62%
(4) Serum ferritin > 800 ug/L

Question 11

What is the treatment for hemochromatosis?

Answer 11

Phlebotomy is used to treat hemochromotosis.

Question 12

What dietary changes are necessary with hemochromatosis?

Answer 12

(1) avoid raw shellfish
(2) Eat less fat and animal protein
(3) Eat more vegetables and fruits
(4) avoid vitamins
(5) Avoid alcohol

Question 13

What are the results of phlebotomy therapy?

Answer 13

phlebotomy will improve most symptoms except cirrhosis and diabetes.

Question 14

How is hemochromatosis screened for?

Answer 14

PCR analysis is used for the HFE mutation

Question 15

What is megaloblastic anemia?

Answer 15

Anemia characterized by macrocytic cells with immature nuclei and mature cytoplasm.

Question 16

What foods contain folate?

Answer 16

Folate is found in liver greens and yeast

Question 17

What is the daily requirement for folate?

Answer 17

100-150 mg

Question 18

Where is folate absorbed in the GI tract?

Answer 18

Folate is absorbed in the duodenum and the jejunum

Question 19

What conditions increase the demand for dietary folate?

Answer 19

(1) pregnancy
(2) increased RBC turnover
(3) Exfoliative dermatitis
(4) Drugs (methotrexate)

Question 20

What conditions can impair the absorption of folate?

Answer 20

(1) tropical sprue
(2) regional enteritis
(3) resection of the small intestines.

Question 21

What conditions predispose to inadequate dietary folate intake?

Answer 21

The elderly, poor, and alcoholics tend to have reduced folate intake.

Question 22

What are the clinical features of Megaloblastic anemia?

Answer 22

(1) insidious onset
(2) Mild jaundice
(3) Glossitis
(4) angular stomatitis
(5) Weight loss
(6) Purpura

Question 23

What are the cellular morphological characteristics of Megaloblastic anemia?

Answer 23

(1) large oval red cells (macrocytosis)
(2) Hypersegmented neutrophils
(3) Abnormal immature nuclei in RBC precursors
(4) mature cytoplasm

Question 24

What are the abnormal lab findings in megaloblastic anemia?

Answer 24

(1) WBC decreased (pancytopenia)
(2) Hgb decreased
(3) Hct decreased (pancytopenia)
(4) Platelets decreased (pancytopenia)
(5) MCV increased
(6) RDW increased
(7) reticulocytes decreased
(8) LDH and bilirubin increased (liver damage)

Question 25

What is the treatment for folate deficiency?

Answer 25

Give 1mg of oral folic acid daily. Cannot give with folate with B12 deficiency as B12 neuropathy may be aggravated.

Question 26

What is the effect of supplementary folate on B12 deficiency?

Answer 26

Supplemental folate will improve anemia of B12 deficiency but may aggravate neuropathy

Question 27

What is the function of B12?

Answer 27

B12 is a coenzyme that helps transfer methyl groups. Important in myelin production

Question 28

How is B12 absorbed?

Answer 28

B12 is bound by R-binder which protects B12 from gastric secretions. In the duodenum IF displaces R binder. IF-B12 complex binds the receptor cubilin in the ileum. This new complex binds amnionless which facilitates the endocytosis of B12.

Question 29

How much dietary B12 is required each day?

Answer 29

1-2 ug

Question 30

Where is B12 absorbed?

Answer 30

In the Ileum.

Question 31

What foods contain B12?

Answer 31

Animal products

Question 32

What gastric surgical disorders can predispose to B12 deficiency?

Answer 32

(1) total gastrectomy (2) blind loop syndrome (3) Ileal resection.

Question 33

What parasites can cause B12 deficiency

Answer 33

Some tapeworms can cause B12 deficiency

Question 34

What non surgical disorders can cause B12 deficiency?

Answer 34

(1) Zollinger Ellison syndrome (pancreatic tumors) (2) Regional enteritis (3) Hypothyroidism (4) drugs (5) tropical sprue (6) Pancreatic insufficieny.

Question 35

What neurological disorders are associated with B12 deficiency?

Answer 35

Loss of proprioreception, parathesias of the hands and feet as well as other nurological symptoms are associated with B12 deficiency.

Question 36

What is pernicious anemia?

Answer 36

Pernicious anemia is an Autoimmune disease with insidious onset which causes atrophy of the gastric mucosa. This leads to B12 deficiency.

Question 37

What is the epidemiology of pernicious anemia?

Answer 37

Pernicious anemia is most common people over 40. Scandanavians are the most susceptible.

Question 38

What causes the autoimmune reaction of pernicious anemia?

Answer 38

Antibodies against the H/K ATPase which cause destruction of gastric mucosa. anti parietal cell and anti IF antibodies are also seen in PA.

Question 39

What various AI diseases are associated with pernicious anemia?

Answer 39

(1) AI thyroid disorders (2) Type I diabetes (3) Hypoparathyroidism (4) Addison disease (5) Ulcerative colitis (6) Vitiligo (7) Acquired agammaglobulinemia.

Question 40

What is the treatment for B12 deficiency?

Answer 40

Intramuscular B12 is the treatment for B12 deficiency

Question 41

What is the schilling test?

Answer 41

Patient drinks radiolabeled cobalamin. IM B12 is then added. Urine is collected. labeled B12 in the urine is indicative of B12 that has been absorbed. Part II involves adding IF and looking for any change in urine B12. Part III involves repeating the procedure after 14 days of antibiotics.

Question 42

What is sprue?

Answer 42

Non-Tropical sprue: An immunological reaction to gluten in the intestines. Tropical sprue: overgrowth of bacteria in the intestines leading to malabsorption.