Absorption 1: Ions and H2O Flashcards

Question

how is iron regulated? what does too much/little iron cause?

Answer 1

Tight regulation of iron is crucial There is no active excretory mechanism for iron once it has entered the body Hereditary haemochromatosis: Too much iron Iron deficiency anaemia: Too little iron (not enough to produce RBC)

Answer 2

Plasma iron pool: The Iron that circulates in blood Large amount of iron in the plasma moves to bone marrow for RBC production (erythropoiesis) When RBCs become senescent, they are engulfed by splenic macrophages Iron is liberated from haemoglobin and enters back into plasma iron pool The liver is a major storage region for iron: When there is excess iron in the plasma pool, the iron is stored in the liver. When plasma iron pool diminishes the iron stored in the liver can be released to top it up. Iron out: We lose very small amounts of iron per day (1-2mg) This is in the form of shedding of skin cells and enterocytes. women lose iron via blood during menstruation Iron in: 1-2mg of iron per day enters our body from our diet to top up the iron we lose.

Answer 3

Inorganic iron Source: green vegetables e.g. broccoli Majority of the iron from these sources is non-absorbable as: A lot of the iron is bound anti-oxidants --> makes iron inert and inaccessible. Inorganic iron is in an Fe3+ state - needs to be reduced to Fe2+ before it can be absorbed Haem iron Source: red meats Haem iron is far more bioavailable (greater absorption) We have equal absorption of haem iron and inorganic iron We eat less meat and more vegetables it balances out There is a gradient of iron absorption from small to large bowel - most absorbed in small, less absorbed in large bowel

Answer 4

Inorganic ferric Fe3+ iron is reduced to ferrous Fe2+ form This is done partly by stomach acid This means iron uptake may be affected for patients who have had gastrectomies PPIs could potentially be used to treat hereditary haemochromatosis The iron is mosty reduced by binding to Dcytb (duodenal cytochrome B) (a ferric reductase) Ferrous (Fe2+) iron can now be absorbed by the enterocyte The iron is taken up by DMT1 (divalent metal transporter 1) The absorbed iron now has 3 possible fates: - Iron used by cell in metabolic processes - Iron stored in cell by being bound to ferritin This storage protein makes iron inert Prevents damage to cells (e.g. DNA damage), as iron drives free radical production - Iron is effluxed out of enterocytes and into the blood through Ferroportin Iron will then be oxidised in the blood and it binds to transferrin (Iron on its own is toxic)

Answer 5

Transferrin receptor mediated endocytosis Cells express transferrin receptor on their cell surface Involves both transferrin receptor, DMT-1 + ferric reductase STEAP-3 This allows them to capture of transferrin-bound iron Iron is liberated from complex Occurs in cells that need iron, e.g. erythroid precursor

Answer 6

Absorption of iron is tightly regulated by hepcidin Hepcidin: (hormone): is an inhibitor of SI iron absorption Made predominantly by liver - hepatocytes Hepcidin Mediates its effects through Ferroportin (it binds to Ferroportin and degrades it so iron can’t be effluxed) High iron levels: High iron sensed by proteins in hepatocyte: TfR2 HFE HJV abnormality in any one of these can disrupt hepcidin production (results in excess iron intake) Hepcidin is produced by hepatocytes --> binds to Ferroportin --> Iron no longer effluxed from enterocyte. Low iron levels: (anaemia, erythropoiesis, hypoxia) Hepcidin is switched off --> increase iron absorption

Answer 7

When you have an infection or inflammation the body triggers Interlukin-6 Interlukin-6 them stimulates hepcidin transcription and translation Hepcidin prevents iron from being effluxed by enterocyte into the plasma pool Hepcidin also binds to Ferroportin on cell surface of macrophages Macrophages would usually efflux iron after engulfing senescent RBCs Due to the binding of hepcidin, the macrophage becomes iron loaded, as iron is trapped so cannot be effluxed into plasma iron pool Lowering plasma iron is useful: Bacteria/pathogens they need iron to survive. Low iron therefore limits bacterial damage and proliferation Also, a depleted plasma iron pool is good because lots of iron makes inflammation worse through driving reactive oxygen species.

Answer 8

Anemia of chronic diseases (ACD) Iron deficiency anaemia (IDA): most common cause is excessive bleeding.

Answer 9

Anaemia of chronic diseases occurs due to chronic infections/inflammations Inflammations/Infections cause an increase in hepcidin which causes a reduction in iron available (it becomes locked away due to mechanisms previously mentioned) This results in anaemia despite there being adequate body iron Obesity causes low grade chronic inflammation which causes increase in hepcidin - anaemia of chronic disease 6 months after restrictive bariatric surgery: decrease in serum hepcidin - improved functional iron status

Answer 10

Haemochromatosis: is a hereditary disease characterised by improper dietary iron metabolism which causes the accumulation of iron in a number of body tissues. Causes for causing HH: Mutation in HFE or HJV or TfR2 means you can no longer sense iron levels - you won’t switch hepcidin on when needed - iron overload. Mutation in hepcidin itself, so it can’t function Mutation in Ferroportin (insensitive to hepcidin) These mutation impact the ability to supress iron at level of enterocyte.

Answer 11

Mechanisms A Hereditary disorder means that the body can’t make hepcidin --> ↑ iron levels --> Iron is stored in the liver (later stored in other organs) However, there is not enough transferrin for all of this iron to bind to in the circulation Unbound iron is toxic (iron drives production of free radicals). This results in organ damage This Iron accumulation can eventually cause end stage organ damage, most importantly in the liver and pancreas This manifests as liver failure and diabetes mellitus respectively

Answer 12

Treatment: Phlebotomy (taking blood) this reduces iron levels as if you take blood, the body makes more RBC using iron. As a result iron is mobilised out of liver. So regular phlebotomy removes excess iron out of organs. Therefore, if you catch Haemochromatosis early, the irreversible effects of iron overload can be avoided (extensive liver damage or extra-hepatic damage)

Answer 13

Fenton reactions (1) Fe2+ + H2O2 → Fe3+ + OH· + OH− (2) Fe3+ + H2O2 → Fe2+ + OOH· + H+ Production of free radicals mediate oxidative stress, cellular damage ( DNA adducts) and eventual cellular death via apoptotic signalling.

Answer 14

Iron deficiency is the most common widespread nutritional disorder in the world Two billion people are anaemic due to iron deficiency IDA is frequently exacerbated by other diseases e.g. malaria, HIV/AIDS, hookworm infestations, schistosomiasis, tuberculosis WHO recommends: Increase iron intake Control infection Improve nutritional status

Answer 15

Effects 2-5% of adult men + post-menopausal women Common cause of referral to gastroenterologists (4-13%) Causes: Menstrual blood loss → commonest cause in pre-menopausal women Blood loss from GI tract (e.g. due to cancer or ulcer) - commonest cause in adult men and post-menopausal women Drugs (chronic NSAID users) → cause blood loss of GI tract - may develop IDA Treatment for IDA: 200 mg iron twice daily plus 250 mg ascorbate (makes iron more bioavailable) for 3 months

Answer 16

Coeliac Disease: An inappropriate autoimmune response to gluten that effects the SI More specifically it results in a reaction to gliadin, a gluten protein found in wheat, barley and rye. Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein + immune system cross-reacts with the bowel tissue causing an inflammatory reaction This Causes villous atrophy and crypt hyperplasia (gives flattened surface epithelium in place of villi) This results in damage to the absorptive surface of intestine meaning you are unable to take nutrients from your food as effectively.

Answer 17

Symptoms: IDA (not absorbing iron due to damage of gut lining) Diarrhoea Weight loss (not accessing nutrition) Fatigue stunted growth in children Only effective treatment is lifelong gluten-free diet

Answer 18

Diagnosis: Test for total immunoglobulin A (IgA), IgG and IgA tissue transglutaminase (tTG) Follow this up with a small bowel biopsy

Absorption 1: Ions and H2O Flashcards

(42 cards)