3.20 NIELL Iron Overload Flashcards
Why is Fe overload bad
-Generated Hydroxyl radicals
–lipid peroxidation, fibrosis, carcinogenesis
Alcohol and Iron
-30% alcoholics have Fe overload
–Possible folate def increases iron absorption
Clinical: skin pig, hypogonadism, glucose intolerance, Most Iron in kupffer cells vs hepatocytes
Thalassemia and IRON!!!!
-Pts receiving transfusion recieve 200-300ml/kg/year
Clinical problems:
- 1st decade with HEPATOMEGALLY (enlarged liver)
- Lack of sexual development (OH NO!!!)
- 2nd decade: Cardiomegally (bad) Treatment: Dextroferramine: Fe chelator
Hereditary Hemachromatosis
Mutation of HFE gene (Auto Recessive w/ reduced penetrance)
-Result: low hepcidin regardless of iron concentration and iron accumulation develops over years b/c absorption from GI tract even with high iron conctration
Hemachromatosis Clinical Symptoms
- Liver Function abnormalities -Arhtralgias
- Weakness and lethargy -Impotence in men
- Skin hyperpigmentation -Electrocardiographic changes
- Diabetes mellitus -Hepatomas (malignant tumor of liver) increase 20 fold
- Present 30-50 yrs old
Hemachromatosis Lab Findings
Normal: WBC, Hematocrit and Platelets
Abnormal:
- Serum Iron .180microg/dl
- Iron binding capacity: normal to low (transferrin is being used up)
- Saturation.62% -Serum Ferritin . 800microg/liter
- Liver biopsy: increased iron
Hemachromatosis Treatment
- Phlebotomy: bleed the bastards
- Aim to keep ferritin <50ng/ml
Diet Restrictions:
- Raw shell fish
- less fat and animal protein
- avoid vit c (increase absorption)
- avoid alcohol (never)
Results of Treatment and what will not improve??
- General Health improves
- Hyperpigmentation lessens
- Arthalgias may disappear
- DIABETES will NOT improve
- Stop cirrohosis of liver
- If treated before cirrhosis, hepatoma will not develop
Screen for Hemachromatosis
- Genetic testing of family to see if they have mutation
- Having mutation does mean pt will develop disease
- Insurance companies do not want to pay for and not much evidence supports this
Folate Deficiencies
- Body stores 10-12mg (small) so def can develop rapidly/3-4 months
- Absorption is duodenum and jejunum
- Main foods: liver, greens and yeast
Candidates for Folate Supplement
People who are/have:
- Pregnant/lactating
- Increased RBC turnover (hemolytic diseases)
- Exfoliative dermatitis
- Drugs: methotrexate
Impaired absorption of Folic Acid
Tropical Sprue
Regional Enteritis
Resection of small intestines
Seen most in: elderly, poor and alcoholics
Treatment of Folate Deficiency
Give 1mg/day of folic acid orally
-Need to be sure it is not B12 def (give B12 and folate together if unsure) b/c of neuropathy
Clinical Features of Megablastic Anemias
- Insidious onset: gradually progressive symptoms
- Mild Jaundice: excess breakdown of hemoglobin resulting from increased ineffective erythropoiesis in the BM
- Glossitis: Beefy red tongue
- Angular stomatitis: corners of mouth
- Weight loss (symptoms of malabsorption)
- Purpura: from thrombocytopenia (less common)
Lab Values of Megablastic Anemias
PANCYTOPENIA
- WBC: low -MCH ([Hgb] per RBC): high, cytoplasm keeps dev but cells are not dividing
- Hgb: low -RDW: high, variation in shape and size
- Hct: low -Retic Count: low, new RBC are not being produced
_-MCV**>98fL (macrocytic)_ -LDH and Bilirubin: High, Marrow cell breakdown
BOOK EXPLANATION OF LAB VALUES
Absorption of B12
B12 Nutritional Aspects
Body Stores 2-3mg, def takes 2-4 yrs to develop
Absorption site: Ileum
Sources:Animal products, Milk, Eggs and Cheese
B12 Def Gastric Disorders
Total Gastrectomy
Blind Loop Syndrome
Zollinger Ellison Syndrome: Gastric producing tumor in pancreas secretes HCL prevents transfer of Cbl from R binders to IF
Intestinal Disorders and other causes of B12 deficincy
Intestinal:
- Ileal Resection
- Regional enteritis
- Cbl malabsorption from hypothyroidism or drugs
- Tropical Sprue
Other:
- pancreatic insufficiency: lack of transfer to IF
- Dietary: fucking vegans (rare)
Main differentiation between B12 and Folate Deficiencies?
B12 have Neurological disorders
EARLY:
- Parathesias of hands and feet
- Somulence and dementia
- Descreased vibritory and proprioception
- Loss of position sense (in dark)
Late:
- Spastic paralysis from demyelination of dorsal and lateral columns - not reversible
- “Combined system disease”
PERNICIOUS ANEMIA
- Cause by auto immunoe attack on the gastric mucosa leading to atrophy of the stomach
- Wall of stomach thins, with plasma cell and lymphoid (CD4) infiltrate of the lamina propria
- Intestinal metaplasia may occur
- SECRETION OF IF IS ABSENT (B12 DEF)
- Antiparietal cell abs in 90% of PA and 60% of atrophic gastritis
- Intrinsic factor abs found in 50-70% of PA
OTHER AUTOIMMUNE DISEASES ASSOCIATED WITH PA
- Auto thyroid disorder
- Type 1 diabetes
- Hypoparathyroidism
- Addison Disease
- Ulcerative colitis
Vitiligo
-Aquired agammaglobulinemia
Schilling Test
PART I:
-Drink cyanocobalamin, 24hr urine collection, at 2 hrs give 1000microg of IM b12, measure in urine
PART II:
-Give 60 mg of hog intrinsic factor with radioactive B12
PART III:
Repeat after 14 days of antibiotics
