4. Glycogen Storage And Hypoglycaemia Flashcards

Question

Megaloblastic anaemia definition.

Answer 1

Bone marrow produces unusually large, structurally abnormal immature rbc (retinaculocytes)

Answer 2

• Vitamin B12 (Cobalmin) and folate (vitamin B9) Deficiency leads to megaloblastic anaemia due to an inability of red cells precursor cells to synthesise DNA and therefore to divide

Answer 3

– large (‘mega’) red cell precursors are released into bloodstream with large nuclei and open chromatin – macrocytic erythrocyte – big blood cell – ovalocytes – oval rbc ○ Have less rbcs as you don't have enough things to produce them – but in response to this bone marrow pushes out rbc earlier than they should be (with large nuclei and chromatin) - not matured

Answer 4

* "Lemon yellow" skin and angular glossitus | * ''Beefy" red tongue – not enough things required for cell turnover

Answer 5

---> It is an increase in the mean red cell volume to above the normal range (greater than 100 femto litres)

Answer 6

* Megaloblastic anaemia * Drugs (antimetabolites, such as hydroxycarbamide, methotrexate, and azathioprim) * Don't give folic acid with methotrexate as it can block folic acid action * Pregnancy and the neonatal period * Severe thyroid deficiency (hypothyroidism) * Smoking

Answer 7

* can be physical or mental * Weak muscles, numb/tingling feeling in hands and feet, nausea, decreased appetite, weight loss, irritability, fatigue, diarrhoea, smooth and tender tongue, fast heart rate

Answer 8

B12 - is only found in aminal products | • Some foods are fortified with vit B- possible to take supplements

Answer 9

1. Either ingested as free B12 or as a complex 2. B12 released from proteins by proteases first form a complex with proteins called haptocorrins (R-binder) • B12 is very sensitive to hydrochloric acid in stomach so it binds to haptocorrins – to help it pass through stomach 3. B12 haptocorrin complex passes through stomach is digested by pancreatic proteases in the small intestine releasing the B12 4. B12 is sensitive so it binds to a glycoprotein called intrinsic factor produced by cells • A deficiency in intrinsic factor results in pernicious anaemia- a lack of vit B12 absorption ○ If cells aren't producing intrinsic factor ○ Or part of the gut producing intrinsic factor has been removed 5. Once internalised B12 forms a complex with transcobalmin and is released in blood for various tissues

Answer 10

– a reversible peripheral neuropathy – subacute combined degeneration of the cord (degeneration of the posterior and lateral columns of the spinal cord), weakness numbness and tingling in legs, arms and trunk, change in mental status and irreversible nervous system damage if you don’t treat in time

Answer 11

* 1. The brain and central nervous system as it helps with the formation of myelin. * To create DNA * Needed for healthy red blood cell formation * Vitamin B12 also helps with digestion * Heart health; a vitamin B12 deficiency can lead to an increased risk for heart disease. * Liver takes up about half of the dietary B12 and acts as a store of this vitamin. Liver can supply B12 requirements of the body for 3-6 years

Answer 12

• Synthesised in bacteria and plants – Consumed from leafy vegetables/grain fortification

Answer 13

• Extreme tiredness, fatigue, pins and needles (paraesthesia), mouth ulcers, muscle weakness, disturbed vision, psychological problems, which may include depression and confusion.

Answer 14

• Required for DNA methylation during development Used in – DNA Creation, – red blood cell formation

Answer 15

* Foetal growth and development are characterized by widespread cell division. * That’s why women who want to get prgantn or are pregnant are asked to increase their follic acid intake

Answer 16

– Arise from failure of embryonic neural tube closure between the 21st and 27th days after conception – Inadequate concentrations of folate in a pregnant woman

Answer 17

1. It transfers a methyl group from L–methyl malonyl - CoA to form Succinyl CoA 2. It is also required for the transfer of a methyl group from tetrahydrofolate (FH4) to homocysteine to form methionine without which can affect folate metabolism (‘trap’ folate):

Answer 18

* 1. Elevated levels of methylmalonyl coenzyme A (CoA) * 2. Homocysteine (amino acid) levels rise: * 3. Folate trap

Answer 19

– DNA and Red Blood Cell production may slow – Methyl folate trap > Associated with inflammation ○ b12 needed to transfer homocysteine to methionine and folate also effects this conversion, if there is not enough B12 to do this conversion , 5 methyl TH4 folate isn't being converted to TH4- folate so there is a build up – Tend to be higher in people with vitamin B12 deficiency

Answer 20

B12 required for transfer of a methyl group from tetrahydrofolate (FH4) to homocysteine to form methionine • Deficiency prevents its use in other reactions (as it is trapped in FH4 stable form) such as nucleotide synthesis required for DNA synthesis • This leads to a ‘functional folate deficiency’ despite good diet of folate

Answer 21

* Low haematocrit * High mean cell volume (bigger cells) * Increase homocysteine amino acid

Answer 22

* Fewer RBC and so lower haematocrit * Larger cells – increased mean cell volume * Hypersegmented neutrophils – more lobes * Increased levels of homocysteine

Answer 23

---> • Folic acid administration alone reverses the hematologic abnormality BUT • masks the B12 deficiency that can then proceed to severe neurologic dysfunction and pathology • Therefore, megaloblastic anaemia should not be treated with folic acid alone • SO treat with Combination of folate and vitamin B12

Answer 24

– For people with no neurological involvement Initially administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks. (patients tend to be complient due to positive effects of injection) The maintenance oral dose depends on whether deficiency is diet related or not. – dietary advice

Answer 25

Thalassaemia --> due to reduced globin chain synthesis • Alpha thalassemia – absence of alpha globin • Beta thalassemia –absence of beta globin

Answer 26

Thalassaemia --> due to reduced globin chain synthesis • Alpha thalassemia – absence of alpha globin • Beta thalassemia –absence of beta globin Anaemia of chronic disease • Hepcidin results in functional iron ddeficiency Iron deficiency • Lack of iron to synthesise heam Lead poisioning • Acquired defect, inhibitis enzymes involved in hame synthesis Sideroblastic anaemia • Inherited defect in haem synthesis ringed sideroblasts

Answer 27

----> free iron is very toxic to cells – can change from Fe2+ to Fe3+ causing oxidative stresss • Can be used by macrophages to destroy bacteria

Answer 28

``` • Oxygen carriers (myoglobin, haemoglobin) • Co factor in many enzymes ○ Cytochrome P450 ○ Krebs cycle ○ Cytochromes ○ Catalase ```

Answer 29

Body can't excrete iron. | - it is constantly recycled and maintained through dietary uptake

Answer 30

Feerous iron – Fe2+ • Reduced form Ferric iron – Fe3+ • Oxidised form Iron musts be reduced to ferrous iron before it can be absorbed from the diet. Can't absorb ferric ion

Answer 31

Iron musts be reduced to ferrous iron before it can be absorbed from the diet. Can't absorb ferric ion • Need 10-15 mg/day dietary iron (higher for menstruating women) (U.K. Dietary Reference Values 8.7mg per day for men and 14.8mg for women) * Greater for women of child bearing age * Absorption occurs in duodenum and upper jejunum (early in small intestine) * Haem iron best source (most readily absorbed)

Answer 32

* Pathogens require iron | * Can be exploited by macrophages and inflammatory mechanisms

Answer 33

* Mix of haem iron (2+) and non haem iron which is a mixture of 2+ and 3+ form * Ferric iron 3+ must be reduced to ferrous iron 2+ before it can be absorbed from diet * Animal sources of iron * Vegetable sources of iron – need something with it like vitamin C to reduce the iron and help absroption

Answer 34

1. Duodenal crypt cells sense iron status through transferrin and gene complex 2. In the apix – ferric iron must be converted to ferrrous iron for absorption 3. Apical Cell is where iron is reduced by reductase • Dietary iron is reduced on brush border • Absorption facilitated by divalent metal transport (DMT1) • Transfer iron via ferritin to ferroportin (dependent on hepcidin) • Hephaestin oxidises iron from ferrous to ferric (fe2+ in the cell and then when transported by transferrin it is fe3+) • Transported as transferrin 4. Hepcidin – can inhibit this, downregulate export of iron through cells, decrease export of iron

Answer 35

* Amount available to absorb – diet * Stores * Bone marrow - erythropoiesis

Answer 36

• Increase vitamin c intake with iron increase iron absorption ○ Vit c helps reduced ferric to ferrous iron

Answer 37

Can bind non-haem iron in the intestine. Reduces absorption Dictary antioxidants • Tannins in tea • Phytates – chapatis and pulses • Fibre • Antacids - Gaviscon creduce iron uptake)

Answer 38

Increase iron absorption Vitamin C and citrate - prevent formation of insoluble iron compounds - help reduce ferric iron- ferrous

Answer 39

* Haemoglobin * myoglobin * Enzymes – cytochromes * Transported iron – transferrin

Answer 40

• Ferritin – soluble | Haemosiderin – insoluble,less available - granuoles found in macrophages

Answer 41

DMT-1 – dimetaltransporter 1 • Takes non bound iron into cells 1. 3+ bound transferrin bind to receptor and enters cytosol with receptor mediated endocytosis 2. 3+ with endosome released by acidic microenvironemnt and reduced to 2+ 3. 2+ transported hy DMT-1 4. In cytosol 2+ stored in ferritin, exported by ferroprolein or taken up by mitochondria to use in cytochrome enzymes

Answer 42

DMT-1 – dimetaltransporter 1 | • Takes non bound iron into cells

Answer 43

• Only gain a very small amount of iron from diet, most are recycled * Old RBC engulfed by macrophages – phagocytosis * Mainly by splenic macrophages and kupffer cells of liver * Macrophages catabolism haem release from bc * Amino acids reused or deaminated by amino acid metabolism * Iron exported to blood by transferrin or returned to storage as ferritin

Answer 44

• Depends on diet, bone marrow, stores | Dietary iron levels sensed by enterocytes

Answer 45

• Regulate transporters - less transports. Less Iron • Regulate receptors • Hepcidin (block export of iron from enterocytes at time of infection - as iron can help bacteria) and cytokines • Crosstalk between epithelail cell and other cells like macrophages =

Answer 46

Increse – in times of iron overload Decrease – when lots of rbc are produced – high erythropoietic activity → Hepcidin induces internalisation and degradation of ferroportin

Answer 47

Causes release of cytokines Causing Increased hepicidin levels – in response to cytokines produced in inflamamtory response • Inhibits ferroportin • Decrease iron release from rectoendothelial system • Decrease iron absorption from gut Cytokines also inhibit erythropoietin production in kidney, decrease erythropoeisis in bone marrow,

Answer 48

``` • Bone marrow --> make new RBC • Macrophages destroy erythrocytes Plasma iron pool – iron 3+ boudn to transferrin Loss of iron Dietary iron absorption Iron stores – lvier ```

Answer 49

* Insufficient iron in diet – vegan and veggie * Malabsorption of iron – vegan and veggie * Bleeding - menustration * Increase requirement – pregnancy, rapid growth * Anaemia of chronic disease - IBD

Answer 50

Is a sign not a diagnosis ○ Need to understand why the patient has low iron ○ Due to maybe diet or pregnancy etc. - what is the reason for iron deficiency

Answer 51

– Infants – Children – Women of child bearing age – Older adults

Answer 52

* Tiredness * Pallor * Reduced exercise tolerance * Caridac – angina, plapitations * Increased respiratory rate * Heafache, dizzyness * Pica = cravings for weird things – dirt, ices * Cold hands and read Epithelail changes • Glossy tongue • Spoon nails

Answer 53

---> can't be excreted ``` Fenton reaction with iron free radicals • Hydroxyl and hydroperoxyl radical can cause damge to cells (oxidative stress) ○ Lipid peroxidarion ○ Damage to proteins ○ Damage to DNA ```

Answer 54

* Dietary advice * Supplements * Iv iron * Intramuscular iron injections * Blood transfusion

Answer 55

* Low iron * Low transferrin * High iron binding capacity

Answer 56

---> accumualtion of iron after regular transfusions Manage with chelating agents to delay effects ``` Problems accumulation of iron can cause: • Liver cirrohsis • Diabetes • Cariomyopathy • Increased skin pigmentation ```

Answer 57

Mutation in HFE - can't bind to transferrin so the negative influence on iron uptake is lost • More iron in cell • More accumulates in end organs Treat with venesection

Answer 58

Why is there only one way to manage Hereditary Haemochromatosis? • No way of excreting iron • Can only lose iron through bleeding as it accumulates Why might venesection need to be repeated? Why might some drugs e.g. proton pump inhibitors reduce the need for venesection? • Ppi raises stomach ph, so more iron remains in ferric form • Lower acid levels, less iron gets broken away from foods.

4. Glycogen Storage And Hypoglycaemia Flashcards

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