Lecture 20 Flashcards
What is the prevalence of iron deficiency?
The most common nutrient deficiency in the world and New Zealand
Aside from iron what other nutrients do New Zealanders consume low amount of?
NZ has low Selenium and iodine dietary intakes
Iodine involved with thyroid function, can develop gouta and hyperthyroidism
Nutrient biomarkers
Iron is the only nutrient that has really good biomarkers
-useful to be able to determine peoples iron levels, and overall health
Major minerals
Present in amounts larger than 5grams (a teaspoon)
A pound is about 454g
-Thus only Ca Calcium and Ph Phosphorous appear in amounts larger than a pound
Calcium 1150g (maintains bone health and bone matrix. Large daily requirement)
Phosphorous 400g
Potassium 210g
Sulfur 90g
Chloride 90g
Magnesium 30g
Trace Minerals
Minerals present in amounts less than 5grams (1 teaspoon) (are over a dozen. Only six shown) -require less on a daily basis -iron is incredibly important so proportionate amount doesnt correlate to non-importance Iron 2.4g Zinc 2.0g Copper 0.09g Manganese 0.02g Iodine 0.02g Selenium 0.02g
Major Iron containing and Iron binding proteins and their functions
- O2 Transport
- Energy metabolism
- Fatty acid metabolism
- DNA and collagen synthesis
Haemoglobin - O2 Transport (vital for life)
Myoglobin - O2 transport in body
Cytochrome oxidase and other cytochromes - Electron Transport
Catalase - Peroxidase reduction (oxidative stress response)
cytochrome P450 - Metabolism of fatty acids, steroids, prostaglandins, leukotrienes
Ribonucleotide reductase- DNA synthesis
Succinate dehydrogenase - oxidation of fatty acids
Procollogen propyl hydroxylase - collagen synthesis
Phenylalanine hydroxylase - Conversion to Tyrosine
Iron Homeostasis
20-25mg iron is recycled daily and used for red blood cell formation
1-2mg iron is required to be absorbed daily to replace losses
-lost through gut via gut enterocyte (normal storage area of iron when isnt required by body) - enterocytes get sloffed off and lost through GI tract in stolls/poo
Iron bioavailability is low but variable, depending on
-Physiological factors
-Dietary factors
Quantity of Iron stores
Erthrocytes -2500mg
Plasma- 4mg
Body Stores- 1000mg
Myoglobin & Respiratory enzymes (related to O2 release in muscles)- 300mg (small amount)
-the remainder we keep continually recycling
Iron regulation
Iron is under tight regulation
-require a small amount of iron daily, because we require most of the iron on the body that we utilise
Red cell Destruction (RBC have high turn over -every 120 days) –RE system–> Plasma –Bone marrow) –> Red cell production
-RBC broken down, iron released and stored and repackaged to make new RBC
-only lose iron through blood loss
-Period Woman- small amounts
-If person has iron deficiency anaemia:
1. Dietary intake of iron
2. Look for cause of Blood loss (cancer of gut-causing increased blood uptake/loss from gut)
Iron Recycling
- Transferring carries iron in blood –>
a) some iron delivered to myoglobin of muscle cells - b) Bone marrow encorporates iron into haemoglobin of RBC and stores excess iron in ferritin (and hemosiderin)–>
- Iron containing hemoglobin in RBC carrier Oxygen–>
a) some losses if bleeding occurs - b) Liver (and spleen) dismantles RBC, packages iron into transferrin, and stores excess iron in ferritin (and hemosiderin)–>
a) some losses via sweat, skin and urine
- -> Transferrin carries iron in blood
What ions is iron specifically associated with?
Transported with Transferrin - new free around body. always attached to protein
Stored with Ferritin
Iron absorption
Iron into food –>
(absorbed in Duodenum) Mucosal cells in the intestine store excess iron in mucosal ferritin in enterocyte (a storage protein)
(when enterocyte is turned over, it is sloffed off and released into digestive tract and lost in stools) –>
a) If body does NOT need iron –> iron is excreted in shed intestinal cells
b) If body DOES need iron –> Mucosal ferritin releases iron to mucosal transferrin (a transport protein), which hands off iron (from ferritin in enterocyte) to another transferrin that travels through the blood to the rest of the body
Iron and Duodenum
Type of iron eaten in diet strongly effects availbility
Haem Iron- from meat/animal sources, redder meat has more heam iron. Relatively bio available. Taken up by gut enterocyte easily (take up 25-30% of haem iron that we digest)
Haem oxygenase reduces Haem iron from Hb, removes it from Hb.
Enters Labile iron pool
-if required by body it is transported out of gut enterocyte through IReg1 Iron Regulatory Transport Protein. Then taken up by Transferrin
-if not required by body, is stored as ferritin, in Iron Fe3+ oxidised state
Non-haem iron: from plant and cereal sources. Needs to be reduced by stomach acidity/HCl + Dietary reducing agents (3+–>2+) before absorbed by gut enterocyte
-Dietary reducing agents eaten in diet, solubilise Iron so can be absorbed into gut enterocyte
Cytrochrome enzymes on enterocyte cell membrane- help reduce 3+ –> 2+
Then transported via DMT1 divalent methyl transport protein –> into gut enterocyte.
Joins current iron in Labile iron pool –> required or not required by body
All cell membranes also have TfR1 Transferrin Receptor proteins- allow uptake of iron into cells
Why don’t we release most of our stored iron into our body?
Because we’re already in Iron Homeostasis
would rather store and lose through Digestive system
Clinical conditions interfering with this gut enterocyte membrane reaction:
1. malabsorption- reduced iron bioavailability
2. Stomach removed- no acidity/HCl produced by stomach. Decreased availability of Non-Haem iron, as absence of reducing agent
Basic Iron Schematic
Iron consumed
Duodenal enterocyte -ferroportin-> BV + transferrin
RBC + Macrophage(take out iron) -ferroportin-> BV + transferrin
Transferrin Receptor on hepatocyte cell membrane attach to transferring –transferring and transferring receptor are encoytosed and iron released inside cell -> hepatocyte Fe storage reservoir (trasnferring leave cell and T receptor returns onto membrane)–ferroportin –> BV
BV RBC
Hepsidin
Regulatory controller of Iron in body
Hormone produced by Liver
Familial/Genetic conditions:
-Heamachromatosis (iron overload) which affects Hepsidin function (does regulate uptake of iron out of gut enterocyte)
-take up iron without regulation, way too much than needed, stored in liver.
-if undiagnosed, amount of Iron in liver causes liver chirrosis and eventually liver cancer
-Treatment: patient Bled off every 6wks -3months. dependent on severity. common condition
Heme vs Non-heme iron
Only foods derived from animal flesh provide heme, but they also contain non-heme iron.
Meat contians both heme and non-heme iron (provides both sources of iron)
All the iron in foods derived from plants are non-heme iron
–>
Heme accounts for about 10% of average daily iron intake, but is well absorbed -more effectively (about 25%)
Non-heme iron accounts for the remaining 90% but is less well absorbed (~17%)
-dont absorb all iron
-major cause of iron deficiency anaemia in NZ is from poor diet
-high risk group for iron deficiency: Vegetarians. Only eat non-heme iron. therefore need to eat alot more of it (as rel. less well absorbed 17%
High risk group for iron deficiency
Vegetarians. Only eat non-heme iron. therefore need to eat alot more of it (as rel. less well absorbed 17%
Factors enhancing Non-heme iron absoprtion
reduce non-heme (3=–>2+) to become more soluble
- MFP (meat factor protein) factor- helps reduce non-heme iron at gut enterocyte level. (public health campiagns targeted at young children, adolesence and pregnant woman)
- Vitamin C- potent enchancer of heme iron absoprtion
- Citric acid from foods
- Lactic acid from foods (yoghurt, feremented milk products)
- HCl from stomach
- Sugars
- must be eaten simultanouesly
Ascorbic acid
Basal absorption of non heme iron , when including ascorbic acid/Vitamin C
- increases significantly
- saturable mechanism (plataeu at Vit C dietary level of 500mg)
Cereal iron
Iron salt/mineral:
- iron sulphate or iron fumerate
- similar to non heme irons (will need to be reduced/solubilised before being absorbed in duodenum)
- if orange orange juice consumed with cereal, will help increase reduction of Iron from F3+ –> F2+ (solubilisation) and therefore increase iron absoprtion
Factors Which inhibit Non-heme iron absoprtion
- Phytates (assoc. with whole grain/fibrous foods)
- Fibres (assoc. with whole grain/fibrous foods)
- Oxalates (spinach. contains so much oxalate that Iron is bound to oxalate, therefore unable to be solubilised for enterocyte uptake)
- Calcium (milk, binds to iron in cereal)
- Phosphorous
- Polyphenols
- Tannins (tea. Bind to iron salts in cereal, reduce bioavailability (renders it insoluble, preventing absorption in duodenum) . Brown rim in cup. Powerful Polyphenol)
Problem with Non-heme iron
Even though available in alot of food
- has a lot of things that reduces its bioavailability in duodenum
- easy nutrient to become deficient in
Absorbable iron
Total iron vs Absorbed iron Comparing standard servings Pork:1.5mg --> 0.5 mg Spinach: 4mg -->0.1mg Fish:1mg --> 0.1mg Bread: 3mg --> 0.1mg Chicken: 2mg --> 1mg Steak:5mg --> 1.5mg -spinach has alot of iron in it, nearly as much per servingas steak, but only absorb minimal 1. Red meat- highest and most bioavailable amount of Iron 2. White meat. some Shell fish
Iron Contamination
Older days
Cookware of iron- heavy pans
when cooking Particularly acidic food, iron would leach out of cooking utensils into food
–good in developing countries and emergencies economies, with major problem of iron deficiencies
Iron Supplements
Will be prescribed if have iron deficiency
Nz iron prescriptions are high dosages (about 300mg per tablet)
-usually also come with Vit C to increase uptake (are a mineral/iron salt, low iron bioavailabilty, therefore need to give large amount of non heme iron/iron salt w. vit C)
Problem: large amount of iron gives gut disturbances
-diarohea/constipation
-cont comply to taking and stop taking them - due to adverse effects
Iron RDIs
RDI dependant oon physiological stages of growth
- Infants breast fed- 0.5mg
- infants born with large amount of iron, given from mother during last trimester of pregnancy. sufficient amount of iron for their iron stores until 6months
- lower requirement, as breast milk iron is like-heme iron (well absorbed) - Infants bottle fed- 3mg
- high amount required as iron in infant formula is iron salt/non-heme iron, not well absorbed, therefore baseline consumption amount is larger - Infants 7-12months- 11mg (rapid growth, massive expansion in Blood volume, therefore increasing iron requirement)
- Children 1-3 years- 9mg
- Children 4-8 years- 10mg
- Teenagers 9-13 years- 8mg
- Woman 14-18 years- 15mg (particularily for girls - menstruation (loss of Iron through lost blood)
- Woman 19-50 years- 18mg
- Men 14-18 years- 11mg
- Pregnancy-27 mg (huge increase)
- Men over 19 years- 8mg
NZ Iron deficiency risk groups
Related to RDI requirement(increase of requirement) daily dietary intake, related to physiological stages of growth
- Infancy
- Adolescnece (particularily female adolesence)
- Pregnancy
- Vegans/Vegeterians
- Ultra Endurance athletes
- increased blood volume, increased heamodilution, increased RBC turnover
- risk of iron deficient
Iron Deficiency
3x stages (adults)
- have really good biomarkers of iron status, good indicators of stages of iron deficiency.
- also good at giving cue as to whether due to chronic dietary cause or acute clinical cause
1. Depleted storage iron - serum ferritin
Iron deficiency in NZ woman
Alot have Stage 1 and 2 Iron deficiency
- if took blood test Hb count would be normal
- Ferritin and Transferrin would be low
- alot of people would be unaware. Low storage iron signs arent very objective. May feel tired- but is a very subjective sign - alot of people are tired but arent iron deficient.
- -know unless have full Blood test/count, to find true iron status, as clinical signs wont ilustrate Stage 1 and 2
- really aware of yourself having anaemia (Less RBC, less Oxygenation, shorter breath, dizzy upon standing up). Obvious clinical signs
Histology Iron Deficiency ANemia
Pale Normal shape Microcytic anaemia - Small RBC (opposite to large irregular folate/B12 deficiency macrocytic)
