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Nutrition and Drug Monitoring > Iron Part 1 > Flashcards

Iron Part 1 Flashcards

1
Q

Which proteins are complexed with irons?

A
  • 65% in haemoglobin (Hb)
  • 30% ferritin/haemosiderin
  • 3.5% myoglobin (Mb)
  • 0.5% haem enzymes
  • 0.1% transferrin
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2
Q

What is the Physiological Iron Requirement?

A
  • Turnover 20-30 mg/day
  • Absorption 1-2 mg/day
    • 5-10% of 10-15 mg in diet
      • 1 mg/day menstruation
      • 1-2 mg/day pregnancy
      • 0.5 mg/day paediatric
  • Losses 1-2 mg/day
    • Intestines, Bile, Skin, Urine
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3
Q

What are causes of increased iron absorption?

A
  • Iron deficiency (up to 30%)
  • Increased erythropoiesis
  • Ingestion of acids, e.g. ascorbate (reduces Fe3+ to Fe2+)
  • Pregnancy
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4
Q

What are causes of decreased iron absorption?

A
  • Decreased erythropoiesis
  • Ingestion of alkalis
  • Ingestion of tea
  • Precipitating agents (phytates, phosphates)
  • Desferrioxamine
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5
Q

What are features of Intracellular Ferritin?

A
  1. Intracellular storage of bioavailable iron
    • Hollow spherical particle found in Hepatocytes, macrophages
    • Solid-state core of up to 4000 Fe3+ ions
  2. 450 kDa, 24 subunits
    • 21 kDa ‘H’ chains, predominate in heart/kidney isoforms
    • 19 kDa ‘L’ chains, predominate in liver/spleen isoforms
  3. Ferroxidase activity
  4. Denatures to hemosiderin
    • Heterogenous aggregate of iron, lysosomal components and other products of intracellular digestion
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6
Q

What are features of plasma ferritin?

A
  • Small amount of ferritin is secreted into plasma
  • L-rich, low iron content, glycosylation slows clearance
  • No role in iron transport or uptake but correlates with total stores
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7
Q

What does low ferritin indicate?

A

Low ferritin indicates iron deficiency

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8
Q

What causes High Ferritin?

A

High ferritin does not necessarily indicate iron overload. Caused by:

  • Redistribution
  • Increased ferritin synthesis
  • Release of tissue ferritin
  • Liver disease
  • Chronic inflammation
  • Malignancy
  • Thyrotoxicosis
  • Alcohol
  • Familial hyperferritinaemia and cataract syndrome
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9
Q

What should be considered with Ferritin >10,000 μg/L?

A

Consider:

  • Still’s disease
  • Haemophagocytic Lymphohistiocytosis
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10
Q

What are investigations for a raised serum ferritin?

A
  • Question alcohol intake and other risk factors for liver disease, transfusion history, family history of iron overload and the presence or absence of type 2 diabetes mellitus, obesity and hypertension, as well as for symptoms and signs that may point to an underlying inflammatory or malignant disorder
  • Initial investigations: FBC & film, repeat ferritin, TSAT, inflammation markers (e.g. CRP), renal/liver/lipid profiles (abdominal u/s if LFT abnormal), glucose, consider hepatitis serology
  • No evidence for therapeutic venesection in non-alcoholic fatty liver disease
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11
Q

What should be done based on the ferritin levels?

A
  • Ferritin <1000 μg/L, normal TSAT, otherwise well: (lifestyle adjustment), repeat in 3–6 months
  • Unexplained persistent hyperferritinaemia (especially >1000 μg/L): refer to a hepatologist
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12
Q

What are features of Transferrin?

A
  • 80 kDa, 6% carbohydrate
  • Reversibly binds 2x Fe3+ and 2x HCO3-
  • 2x N-linked bi/tri-antenarry glycans
    • Determines half-life
    • Variants – serum/CSF, alcohol, polymorphisms, inborn errors
  • Recycled approximately 500 times
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13
Q

How is Serum Iron assessed?

A
  • Predominantly reflects transferrin-bound iron = in-use iron binding capacity
  • Requires a fasted sample otherwise if a patient has a large iron load in food, it will go up as a measurement otherwise even if the patient is low in iron
  • Colorimetric, atomic absorption spectroscopy, ICP-MS
  • (Abdominal x-ray if acute toxic ingestion suspected)
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14
Q

How is Transferrin and Ferritin measured?

A

Specific immunoassay

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15
Q

What is the Unsaturated Iron Binding Capacity (UIBC)?

A
  • The unused iron binding capacity. Measures the unbound tranferrin
  • Measured as the amount of Fe3+ taken up (by transferrin) at alkaline pH
  • Fallen out of favour.
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16
Q

What isTotal Iron Binding Capacity (TIBC)?

A

Total available iron if all binding sites (principally transferrin) fully saturated

Measured as iron concentration when sample saturated with added Fe3+

  • If Calculated from UIBC
    • TIBC = UIBC + [Iron]
  • If Calculated from transferrin
    • TIBC (umol/L) = transferrin (g/L) x 24.7
17
Q

How is transferrin calculated from TIBC?

A

Transferrin (g/L) =0.0007 x TIBC (ug/L)

18
Q

How is %transferrin saturation calculated?

A
  • 100 x [Iron]/TIBC
19
Q

What causes secondary iron overload?

A
  1. Excess iron intake
    • Dietary: Drinking beer brewed in iron containers
    • Supplements or injections
    • Transfusion-related siderosis
    • Long-term dialysis
  2. Sideroblastic anaemia
  3. Ineffective erythropoiesis
  4. Porphyria cutanea tarda
20
Q

What causes Primary Iron Overload?

A
  • Hereditary haemochromatosis: HFE, TFR2 & gain-of-function Ferroportin defects\
  • African iron overload
  • Juvenile haemochromatosis: Haemojuvelin (BMP coreceptor) & Hepcidin defects
  • Neonatal haemochromatosis
  • Acaeruloplasminaemia
  • Hyperferritinaemia-catarract syndrome: Ferritin L-chain defects
  • Erythropoietic protoporphyria: Mitoferrin defects
  • Atransferrinaemia: Transferrin defects
  • Macrophage-predominant iron overload:
  • Ferroportin loss-of-function
  • Anaemia with iron overload and sideroblasts: Glutaredoxin 5 defects
  • Friedreich ataxia: Frataxin defects (mitochondrial iron chaperone)
21
Q

What is the pathogenesis of Hereditary haemochromatosis?

A
  • Inherited progressive iron overload due to increased iron uptake 3-4 mg/day: positive iron balance 400-1000 mg/year
  • Lipid peroxidation in the liver so cellular injury leading to fibrosis
  • Iron deposition: Liver (90%), Endocrine glands, Joints, Heart
  • Menstruation has positive effect.
22
Q

What is the classican triad of Hereditary Haemochromatosis?

A
  • Pigmentation (‘bronzing’)
  • Diabetes
  • Cirrhosis

​

  • Hypothyroidism
  • Hypogonadism
  • Cardiomyopathy
23
Q

What are common symptoms of Hereditary haemochromatosis?

A
  • Fatigue
  • Weight loss
  • Weakness
  • Arthralgia
  • Oligo/amenorrhoea
  • Erectile dysfunction
24
Q

What are investigations for Hereditary haemochromatosis?

A
  • FBC, LFT, TSAT
  • High transferrin saturation and serum ferritin
  • (Liver biopsy, hepatic stored iron)
  • MRI scan
  • (Genetic testing): HFE gene defects have low penetrance. Only C282Y homozygotes generally develop clinical disease
  • Exclude other causes of iron overload
25
Q

What are the genetics of Hereditary Haemachromatosis?

A

HFE gene defects predominate: Very high prevalence in north European descent (polymorphisms)

  1. HFE C282Y: HFE protein cannot bind B2-microglobulin
    • HFE cannot stabilise in cell membranes
    • Unregulated TFR-mediated intestinal iron uptake
  2. HFE H64D
    • HFE binds TFR but lacks high degree of inhibition
26
Q

What the different variations of HFE gene defects?

A

1 copy C282Y

  • Carrier of the C282Y variant; no increased risk of developing hereditary HC
  • 25% of individuals may exhibit mild/moderate iron overload
  • Complications due to iron overload are rare
  • May be influenced by additional factors( genetic, environmental)

1 copy C282Y, 1 copy H63D

  • Excludes the most common cause of hereditary HC
  • May predispose to mild/moderate iron overload
  • If iron overload, consider other contributing factors
  • If severe iron overload, consider rare genetic causes
  • Consider family testing for iron overload

2 copies C282Y

  • Reported in approximately 90% of hereditary HC patients
  • Investigate for iron overload
  • Consider family testing for iron overload
27
Q

What is the treatment for Hereditary Haemachromatosis?

A

Reduce the amount of iron present

  • Therapeutic phlebotomy - weekly venesection and FBC
    • Ferritin 20-30 μg/L and TSAT <50% (monthly TSAT)
    • Blood donation opportunity
  • Iron chelation (desferrioxamine)

Avoid alcohol

‘Minihepcidins’

Nutrition and Drug Monitoring (17 decks)

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