Minerals And Nutritional Anemias Flashcards
What are the functions and deficiency syndromes of iron?
Functions: Essential component of hemoglobin and iron- containing metalloenzymes
Deficiency symptoms: Hypochromic microcytic anemia
What are the functions of copper and its deficiency symptoms?
Function: Component of cytochrome c oxidase, dopamine β- hydroxylase, tyrosinase, lysyl oxidase, and involved in cross-linking collagen and keratin
Deficuency symptoms: Muscle weakness, neurologic defects, hypopigmentation, abnormal collagen cross-linking
Describe the effects of copper
- Cofactor in redox reactions
- Lysyl oxidase
- Collagen Synthesis (Covalent cross-links) – Differentiate from vitamin C
- Tyrosinase (Melanin synthesis)
- Cytochromes (Electron transport chain)
- Superoxide dismutase (Scavenger of reactive oxygen species)
- Lysyl oxidase
- Forms ceruloplasmin in liver (copper transport protein)
- Helps in iron metabolis
Summarize copper metabolism
- Dietary copper transported to liver bound to albumin
- In hepatocytes, forms ceruloplasmin (secreted into plasma) (requires Copper transporting ATPase)
- Aged ceruloplasmin taken up by liver from plasma and copper secreted into bile (requires Copper transporting ATPase)
What is the role of ceruloplasmin in iron metabolism?
- Ceruloplasmin (ferroxidase) converts ferrous iron to ferric form
- Converts ferrous (absorbed iron) to ferric form and incorporates ferric iron into transferrin for transport of iron
- Mobilizes ferric ions from ferritin and hemosiderin
- Ceruloplasmin is a serum protein (a2-globulin)
- Acute phase protein
What are the manifestations of copper deficiency?
- Microcytic anemia (smaller RBCs)
- Ceruloplasmin (ferroxidase) required for iron mobilization
- Copper deficiency affects iron mobilization
- Degradation of vascular tissue – decreased lysyl oxidase activity.
- Increased risk of bleeding/ hemorrhage
- Defects in hair: Hypopigmented discolored hai
What is Menkes syndrome (Menke kinky hair syndrome)?
- Inherited defect in dietary copper absorption
- Low plasma copper levels
- X-linked disorder
- Hair twisty, grayish and “kinky” (Tyrosinase)
• Aneurysms and neurological dysfunction
(low lysyl oxidase activity)
• Early age of presentation (1-2 years)
What is Wilson disease?
- Autosomal recessive disorder
- Accumulation of copper in liver, brain and eye
- Mutation of copper transporting ATPase (ATP7B gene)
- Over 30 mutations (Allelic heterogeneity)
- Attaches copper to ceruloplasmin and excretes copper into bile
Outline the cause of Wilson disease
- Defective biliary copper excretion
Defective copper incorporation into ceruloplasmin - Accumulation of toxic levels in liver
- Liver damage – hepatitis and cirrhosis (presenting symptom)
- Excess copper spills into plasma
- • Eye: Kayser-Fleischer rings in cornea
• Brain: Neurological damage causing
neuropsychiatric symptoms (basal ganglia)
Describe the lab diagnosis of Wilson disease
Lab Diagnosis
- Decreased serum ceruloplasmin
- Increased urinary excretion of copper
- Increased hepatic copper content
What are the Corneal findings of Wilson disease?
Kayser-Fleischer (KF) rings – Copper deposits in cornea
Patients with Kayser-Fleischer rings usually have basal ganglia (CNS) involvement
What is the significance of iron?
-Heme synthesis- Hemoglobin, myoglobin (in muscle)
- RBCs contain hemoglobin (Largest storage form for iron)
- Loss of RBCs results in loss of iron
- For Redox reactions and component of cytochromes of electron transport chain
Describe dietary intake
- Tightly regulated by body iron stores
- Intestinal mucosal cells are iron sensors (requires HFE)
- Higher body iron stores; less iron absorbed in intestine
- Heme iron (red meat) absorbed better than inorganic iron (vegetarian)
- Inorganic iron in ferrous form is absorbed
- Ferric iron changed to ferrous iron in stomach
- low pH in stomach and dietary vitamin C
- Vegans risk of iron deficiency (high content of phytate and oxalate)
Explain iron transport and storage
Ceruloplasmin (ferroxidase) converts ferrous iron to ferric iron
which is incorporated to transferrin
- Transferrin (transport protein) for ferric ion in plasma
- B-globulin serum protein
- Iron stored in liver and RES as ferritin and hemosiderin (ferric)
- Tiny amounts of ferritin in blood – Measurement of serum ferritin levels indicators of body iron s
What are the lab tests for iron status?
Serum ferritin levels indicator of iron stores (Normal: 50-300 ng/ml)
• High serum ferritin in iron overload (hemochromatosis)
• Low serum ferritin in iron deficiency anemia
- Serum iron (remember, iron is bound to transferrin)
- Low serum iron levels in iron deficiency anemia
- High serum iron levels in iron overload (hemochromatosis)
- Transferrin saturation and Total iron binding capacity
- Hemoglobin levels and hematocrit
- MCV, MCHC – Red cell indicators of RBC size and hemoglobin concentration
What is the logic behind lab tests for iron status?
- Serum iron: Iron bound to transferrin (Normal: 50-150 g/dL)
- Serum iron decreased in iron deficiency anemia
- Serum iron increased in iron overload
Ug/dl - TIBC increased in iron deficiency anemia
- TIBC decreased in iron overload
• Percent saturation of transferrin: Percent of transferrin binding sites occupied by iron. Normally 1⁄3 binding sites
saturated with iron (Normal: 30% transferrin saturation) Total Iron Binding Capacity (TIBC) Explained
• Transferrin saturation decreased in iron deficiency anemia
• Transferrin saturation increased in iron overload
What causes iron deficiency anemia?
• Most common nutritional deficiency
• Reduced dietary iron absorption: Vegans, low dietary vitamin C, achlorhydria
(low stomach HCl), high dietary fiber
• Infants, pregnant women and blood donors at risk
• Chronic bleeding: Increased menstrual bleeding, uterine fibroids, GI bleeding
(ulcer/ cancer), parasitic infestation
What are the clinical features of iron deficiency anemia?
Clinical features: • Iron deficiency anemia – hypochromic microcytic • Fatigue and pallor • Weakness, dizziness • Brittle nails • Pica (appetite for soil
What are the lab tests of iron deficiency anemia?
Low serum ferritin levels (indicate low body iron stores)
Low serum iron levels
- Low percent saturation of transferrin (<20%)
- Increased TIBC
- Low hemoglobin levels; low hematocrit
- Low MCV (microcytic anemia) and low MCHC (hypochromic anemia)
- Bone marrow iron stores - low
What are the dietary modifications for management of iron deficiency?
- Supplement iron rich foods
* Increase availability of dietary iron – vitamin C; Include heme iron (animal sources); Reduce dietary fiber
What is hereditary hemochromatosis (iron overload)?
- Autosomal recessive disorder; Common in Caucasians
- Excessive iron absorption (HFE gene mutation)
- Most frequent mutation is C282Y allele of HFE
- However, other mutations are known (allelic heterogeneity)
- Many are compound heterozygotes
- Delayed age of onset
- Males affected earlier than females – variable expressivity • Excessive accumulation of iron in skin, liver and pancreas
What are the clinical features of hereditary hemochromatosis(iron overload)?
Excess iron causes free radical formation and DNA damage
Clinical Features: http://www.hemochromatosis.org/#videos
• More common in males; presenting age 40
- Acute synovitis or chronic joint pain (knuckles)
- Chronic fatigue (difficult to diagnose)
• Hepatomegaly; Liver damage – cirrhosis; hepatocellular
carcinoma
- Diabetes – destruction of beta cells of pancreas
- Cardiac dysfunction
- Brownish skin pigmentation (Bronze orange color of skin)
- ‘Bronze Diabetes’
What are the lab tests for hereditary hemochromatosis?
- High serum ferritin levels – indicate excessive iron stores
- High serum iron levels
- Transferrin saturation (>50%)
- TIBC is decreased
Describe the management of hereditary hemochromatosis?
- Phlebotomy – removal of blood (donation of blood)
- Dietary modifications – Reduce dietary iron content and iron absorption from diet
- Reduce red meat (iron in meat is better absorbed)
- High fiber content (fiber reduces iron absorption)
What is nutritional anemia?
- Anemia is a clinical sign
- Reduced red cell mass
- Hemoglobin levels <12 g/dL; and/ decreased RBC count
- Measure hemoglobin concentration, hematocrit and RBC count
- Erythropoiesis (RBC formation) in bone marrow depends on availability of nutrients, growth factors and precursor cells
- Reduced nutrient availability results in nutritional anemia
How is nutritional anemia classified based on MCV?
• Nutritional anemias based on RBC size
• Microcytic anemia (<80) due to reduced heme synthesis.
• Also seen in lead poisoning
• Macrocytic anemia (>100) due to reduced cell
division.
• Normocytic anemia (Normal MCV) – Protein energy malnutrition (PEM
What is the type of anemia and lab test of pyridoxine deficiency?
Microcytic anemia
Low MCV; Elevated Homocysteine; Iron parameters - Normal
What type of anemia and lab tests are done for copper deficiency?
Microcytic anemia
Low MCV; Low serum copper
What are the types of anemia and lab tests. Done for vitamin B12 deficiency?
Macrocytic, megaloblastic anemia; Neuropsychiatric manifestations
Lab test: MCV – Increased; Increased Homocysteine; Increased methylmalonate; Low Vitamin B12 levels
What are the types of anemias and lab tests of folic acid deficiency?
Macrocytic, megaloblastic anemia
MCV – Increased; Increased Homocysteine; Methylmalonate - Normal; Low Folic acid levels; Normal vitamin B12 levels
Compare macrocytic anemias in folate deficiency and vitamin B12 deficiency
Vitamin B12 deficiency
• Clinical features: Anemia with associated neurological features
• Anemia – Macrocytic (MCV increased) and megaloblastic bone marrow
• Serum homocysteine and serum methylmalonate levels are elevated
• Anemia is due to folate trap
• Neurological features may be due to accumulation of methylmalonate (affects myelination)
• Risk factors: Parietal cell destruction (pernicious anemia); ileal mucosal disease or resection; vegan diet
• Serum vitamin B12 levels are low
Folate deficiency
• Clinical features: Macrocytic anemia
• Anemia – Macrocytic (MCV increased)
and megaloblastic bone marrow
• Serum homocysteine levels are elevated; Serum methylmalonate levels are normal
• Anemia is due to folate deficiency
• Risk factors: pregnancy, malabsorption syndrome, folate antagonist treatment
• Serum folate levels are low
