Iron Overload and Megaloblastic Anemia: White Flashcards
What effects can unbound iron have on tissues?
(1) lipid peroxidation
(2) Fibrosis
(3) Carcinogenesis
What is the effect of alcohol on iron?
(1) 30% of chronic alcoholics have iron overload
(2) Folate deficiency increases iron absorption
What are the clinical findings of anemia due to alcoholism?
(1) Skin pigmentation
(2) hypogonadism
(3) glucose intolerance
(4) Iron in Kupffer cells.
Why does thalassemia lead to iron overload?
Abnormal red blood cells have decreased survival time and are degraded at an increased rate leading to iron accumulation.
What clinical problems are associated with thalassemia iron overload?
(1) 1st decade hepatomegaly
(2) lack of sexual development
(3) 2nd decade Cardiomegaly
What is hemochromotosis?
Hemochromatosis is a disorder that results in iron overload caused by an autosomal recessive mutation in the HFE gene. (variable penetrance)
What is the result of HFE mutation?
A mutation in HFE results in low hepcidin. Low hepcidin causes the accumulation of iron over time. Constant abosrption
What is the result of iron overload in various tissues?
(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.
What are the clinical symptoms of hemachromatosis?
(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%
What are the unusual laboratory findings in hemochromatosis?
(1) Serum iron in excess of 180dl
(2) TIBC normal to low
(3) % saturation > 62%
(4) Serum ferritin > 800 ug/L
What is the treatment for hemochromatosis?
Phlebotomy is used to treat hemochromotosis.
What dietary changes are necessary with hemochromatosis?
(1) avoid raw shellfish
(2) Eat less fat and animal protein
(3) Eat more vegetables and fruits
(4) avoid vitamins
(5) Avoid alcohol
What are the results of phlebotomy therapy?
phlebotomy will improve most symptoms except cirrhosis and diabetes.
How is hemochromatosis screened for?
PCR analysis is used for the HFE mutation
What is megaloblastic anemia?
Anemia characterized by macrocytic cells with immature nuclei and mature cytoplasm.
What foods contain folate?
Folate is found in liver greens and yeast
What is the daily requirement for folate?
100-150 mg
Where is folate absorbed in the GI tract?
Folate is absorbed in the duodenum and the jejunum
What conditions increase the demand for dietary folate?
(1) pregnancy
(2) increased RBC turnover
(3) Exfoliative dermatitis
(4) Drugs (methotrexate)
What conditions can impair the absorption of folate?
(1) tropical sprue
(2) regional enteritis
(3) resection of the small intestines.
What conditions predispose to inadequate dietary folate intake?
The elderly, poor, and alcoholics tend to have reduced folate intake.
What are the clinical features of Megaloblastic anemia?
(1) insidious onset
(2) Mild jaundice
(3) Glossitis
(4) angular stomatitis
(5) Weight loss
(6) Purpura
What are the cellular morphological characteristics of Megaloblastic anemia?
(1) large oval red cells (macrocytosis)
(2) Hypersegmented neutrophils
(3) Abnormal immature nuclei in RBC precursors
(4) mature cytoplasm
What are the abnormal lab findings in megaloblastic anemia?
(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)
What is the treatment for folate deficiency?
Give 1mg of oral folic acid daily. Cannot give with folate with B12 deficiency as B12 neuropathy may be aggravated.
What is the effect of supplementary folate on B12 deficiency?
Supplemental folate will improve anemia of B12 deficiency but may aggravate neuropathy
What is the function of B12?
B12 is a coenzyme that helps transfer methyl groups. Important in myelin production
How is B12 absorbed?
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.
How much dietary B12 is required each day?
1-2 ug
Where is B12 absorbed?
In the Ileum.
What foods contain B12?
Animal products
What gastric surgical disorders can predispose to B12 deficiency?
(1) total gastrectomy
(2) blind loop syndrome
(3) Ileal resection.
What parasites can cause B12 deficiency
Some tapeworms can cause B12 deficiency
What non surgical disorders can cause B12 deficiency?
(1) Zollinger Ellison syndrome (pancreatic tumors)
(2) Regional enteritis
(3) Hypothyroidism
(4) drugs
(5) tropical sprue
(6) Pancreatic insufficieny.
What neurological disorders are associated with B12 deficiency?
Loss of proprioreception, parathesias of the hands and feet as well as other nurological symptoms are associated with B12 deficiency.
What is pernicious anemia?
Pernicious anemia is an Autoimmune disease with insidious onset which causes atrophy of the gastric mucosa. This leads to B12 deficiency.
What is the epidemiology of pernicious anemia?
Pernicious anemia is most common people over 40. Scandanavians are the most susceptible.
What causes the autoimmune reaction of pernicious anemia?
Antibodies against the H/K ATPase which cause destruction of gastric mucosa. anti parietal cell and anti IF antibodies are also seen in PA.
What various AI diseases are associated with pernicious anemia?
(1) AI thyroid disorders
(2) Type I diabetes
(3) Hypoparathyroidism
(4) Addison disease
(5) Ulcerative colitis
(6) Vitiligo
(7) Acquired agammaglobulinemia.
What is the treatment for B12 deficiency?
Intramuscular B12 is the treatment for B12 deficiency
What is the schilling test?
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.
What is sprue?
Non-Tropical sprue: An immunological reaction to gluten in the intestines.
Tropical sprue: overgrowth of bacteria in the intestines leading to malabsorption.
