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Yr 2 MCD - Haem > 9 - Iron Deficiency > Flashcards

9 - Iron Deficiency Flashcards

1
Q

What proteins in the body contain iron?

A

Haemoglobin

Myoglobin

Ribonucleotide reductase

Cyclo-oxygenase

Succinate dehydrogenase

Cytochrome a,b,c

Cytochome P450

Catalase

Myoglobin

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2
Q

What is the biggest reservoir of iron in the body?

A

Haemoglobin

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3
Q

What is the role of iron in haemoglobin?

A

Holds onto oxygen

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4
Q

What are the consequences of low iron in the body?

A

Low iron = low Hb = anaemia

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5
Q

How is iron incorporated into haemoglobin?

A

Iron in centre protoporphyrin ring within HAEM

Haem is the red part of haemoglobin

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6
Q

How long do red cells live for?

A

120 days

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7
Q

How much iron do we need to make red cells per day?

A

20mg/day

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8
Q

Why do we not need to consume 20mg of iron per day to continue making red cells?

A

Iron is recycled so some of the iron requirement for the day comes from previous days

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9
Q

How much iron do men and women need to consume per day?

A

Men = 1mg/day Women = 2mg/day

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10
Q

How is iron recycled?

A

During red blood cell breakdown, the iron is removed from the cells and conserved

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11
Q

What causes loss of iron on a daily basis?

A

Desquamated cells of skin and gut

Bleeding through menstruation

Pathological loss sometimes

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12
Q

How much iron is provided by the average human diet per day?

A

12-15mg/day

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13
Q

What natural foods does iron occur in?

A

Meat and fish (haem iron)

Vegetables

Whole grain cereal

Chocolate

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14
Q

Despite people consuming a larger amount of iron than needed on average per day, why do many people still suffer iron deficiency?

A

Because most iron eaten does not get absorbed

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15
Q

What occurs if a person has low iron?

A

They have low haemoglobin as a result and so become anaemic

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16
Q

Outline the composition of the haemoglobin protein molecule

A

Haemoglobin:

  • is a composite protein (consists of globin protein chains and haem groups, containing iron)
  • consists of a ring of carbon, hydrogen and nitrogen atoms
  • in its centre is an iron atom in the ferrous (Fe2+) state.

Haem:

  • haem groups are associated with a single globin chain
  • haem sits in a pocket formed by the globin chain
  • is responsible for the red colour of haemoglobin
  • haem combines reversibly with oxygen

In the final haemoglobin molecule, the haem groups are near the surface of the molecule

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17
Q

Outline normal iron haemostasis in the body

A

To re-make huge numbers of red cells on a daily basis, you need 20mg iron every day

  • not possible to absorb this amount or iron daily
  • iron is recycled when red cells are broken down, and used to make new cells
  • unfortunately, iron is also lost in some form everyday

GOOD NEWS:

  • normal human diet provides 12-15mg or iron every day

BAD NEWS

  • it’s difficult to absorb iron
  • most iron eaten is not absorbed
  • we cannot absorb iron in the ferric (Fe3+) state
  • we can only absorb ferrous (Fe2+) iron
  • when you eat, it depends on what else you have in the food that will determine the level of absorption. E.g. orange juice helps to increase Fe2+, tea increases Fe3+.
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18
Q

What is the advantage of eating meat and fish when it comes to iron absorption from food?

A

The advantage of eating meat and fish is that iron has already been incorporated in the haem group

If you eat meat and fish, you are essentially eating haem – this is very easy to absorb

Absorption of iron is very good when you eat meat and fish due to this haem form

Vegetarians need to be more careful

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19
Q

What factors affect iron absorption?

A

DIET

Increase haem iron in the diet and ferrous iron

INTESTINE

Acid in the duodenum, the ligand (meat)

SYSTEMIC FACTORS

Iron deficiency, anaemia/hypoxia and pregnancy

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20
Q

What happens to your iron absorption if you’re anaemic, hypoxic or pregnant?

A

If you are anaemia/hypoxic or pregnant, you absorb MORE iron. This is for compensation.

It is important to note that there are NO REGULATED MECHANISMS FOR IRON EXCRETION so absorption is particularly important.

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21
Q

How do gut cells alter iron absorption?

A

There are proteins sitting at the bottom of the small intestine.

STEP 1:

  • iron is absorbed from the gut lumen into cells.

STEP 2:

  • iron needs to be transported by ferroportin
  • levels of transport are regulated by hepcidin.
22
Q

What is ferroportin?

A

FERROPORTIN

  • this is the iron transporter protein
  • is controlled by a peptide hormone: hepcidin (25 amino acids)
23
Q

What is hepcidin?

A

25 amino acid protein

“The master controller of iron homeostasis”

Hepcidin binds to and induces degradation of ferroportin.

When this happens iron is stuck in the enterocytes and when it is shed the iron is effectively lost from the body.

High hepcidin leads to a decrease in iron entering the blood from the duodenum, macrophages and from hepatocytes.

24
Q

What happens to hepcidin if iron levels are high?

A

If iron levels are high:

  • hepcidin levels increase
  • this blocks the ferroportin
  • stops you from absorbing iron.

There are several proteins involved in the cycle, which have iron-responsive elements.

25
Q

Where is ferroportin found?

A
  1. Enterocytes of the duodenum
  2. Macrophages of the spleen, which extract iron from old or damaged cells
  3. Hepatocytes
26
Q

What is transferrin and what is its role in iron haemostasis?

A

When Fe enters the blood, it binds to transferrin protein (transferrin holds onto Fe in the circulation)

Generally, transferrin is not fully saturated with iron (only 20-40% saturated with iron)

In hospitals, we record the transferrin, the total iron binding capacity, and the transferrin saturation

Transferrin forms stable complexes with iron and more than 40 other metal ions

It cannot transport iron inside the cells where it is needed

Transferrin-iron interacts with the transferrin receptor and the whole transferrin complex is internalised

As the pH drops iron is released and transferrin receptors are recycled

27
Q

In what situations is iron potentially toxic and insoluble?

A

Iron binding proteins and transport systems maintain iron in a soluble and non-toxic form.

28
Q

What is erythropoietin?

A

Hormone

Made in the kidney (mainly) and liver.

Increased amounts of erythropoietin are produced in anaemia.

ANAEMIA

  • leads toTISSUE HYPOXIA
  • leads to INCREASED ERYTHROPOIETIN
  • acts on red cell precusors.
29
Q

What is Anaemia of Chronic Disease (ACD) and what conditions are associated with it?

A

ACD is anaemia is patients who are unwell

It does not result from bleeding, marrow infiltration of disease or iron/B12/folate deficiency

There is no obvious cause for ACD other than that the patient is ill

Associated conditions:

  • Chronic infections (TB/HIV)
  • Chronic inflammatory disorders (rheumatoid arthritis, systemic lupus erythematosus)
  • Underlying malignancy
  • Miscellaneous things (e.g. someone with cardiac failure may get ACD)
30
Q

What laboratory signs can indicate “being ill”?

A

C-reactive protein increases during illness

Erythrocyte sedimentation rate – increased ESR due to increased inflammatory proteins

Acute phase response increases in: ferritin, Factor VIII, fibrinogen and immunoglobulins

31
Q

What causes Anaemia of Chronic Disease (ACD)?

A

ACD is underpinned by cytokine release that occurs in patients that are unwell

Cytokines prevent the usual flow of iron from the duodenum to the red cells, and therefore block iron utilisation

Cytokines include TNF alpha and interleukins

CYTOKINES DO SEVERAL THINGS:

  • stop erythropoietin increasing
  • stop iron flowing out of cells
  • increase production of ferritin
  • increase death of red cells

THEREFORE:

  • make less red cells
  • more red cells die
  • less availability of iron (it is stuck in the cells or with ferritin).

In normal anaemia, erythropoietin increases in order to boost red cell production. In ACD however, this increase in erythropoietin is blunted – this is one of the things that contributes to a persisting anaemia.

32
Q

List the overall causes for anaemia

A

Iron Deficiency

Anaemia of Chronic Disease

33
Q

What are some causes for iron deficiency?

A

BLEEDING

  • most common
  • e.g. menstrual blood loss, GI bleeding and pregnancy-associated blood loss

INCREASED USE

  • e.g. rapid growth (e.g. in adolescence)
  • e.g. pregnancy (the baby takes iron preferentially)

DIETARY DEFICIENCY

  • e.g. in vegetarianism

MALABSORPTION OF IRON

  • e.g. in coeliac disease
34
Q

What is the commonest cause of anaemia?

A

Iron Deficiency

35
Q

What are some useful investigations to consider when potentially diagnosing iron deficiency anaemia?

A

In a menstruating woman over 40, or someone with heavy periods or multiple pregnancies who has NO GI symptoms – don’t do anything. You won’t need to do extra tests to see why this person has iron deficiency.

You may ask if patients there is blood in the urine or faeces, and may check for antibodies for coeliac disease.

36
Q

When would you do a full GI investigation?

A
  • The patient is male
  • The patient is a woman over 40, or a post-menopausal woman
  • The patient is a woman with scanty menstrual loss

Otherwise, iron deficiency anaemia is probably due to menstruation in the patient.

37
Q

What are the full GI investigations done in some iron deficiency anaemia cases?

A

Upper GI endoscopy – oesophagus, stomach and duodenum

Take a duodenal biopsy

Colonoscopy

38
Q

What is done if there are no GI abnormalities in a patient with iron deficiency anaemia which is not due to menstruation?

A

If there are no GI abnormalities, and coeliac antibodies are not present, you can look at the small bowel.

It is unusual to bleed in the small bowel.

Give patient a small bowel meal (drink a radio-opaque substance) and follow through.

39
Q

What laboratory parameters are important in anaemia?

A
  • Mean cell volume (MCV)
  • Serum iron
  • Ferritin
  • Transferrin (= total iron binding capacity, TIBC)
  • Transferrin saturation
40
Q

Why does low haemoglobin and low MCV not tell you for sure that the patient is iron deficient?

A

This is because there is more than one cause of a low MCV.

Iron deficiency is only one of the causes for low MCV.

Need to look at other parameters to determine why the patient has a low MCV. This includes looking at serum iron, ferritin, transferrin (TIBC) and transferrin saturation.

41
Q

What are the 3 causes of low MCV?

A
  1. Iron deficiency
  2. Thalassaemia trait (heterozygous)
  3. Anaemia of chronic disease (low or normal MCV)
42
Q

In what order would you look at laboratory parameters during iron deficiency anaemia diagnosis?

A
  1. Look at MCV
  2. If we further learn that the serum iron is low, this is still not enough to tell if the patient is iron deficient
    * This is because we also see low serum iron in ACD (in thalassaemia trait, serum iron is normal)
  3. If we want to confirm thalassaemia trait, we use Hb electrophoresis – this confirms additional Hb types
  4. We can check ferritin – ferritin is LOW in iron deficiency and HIGH in chronic disease
  5. CRP and ESR
  • may be raised in chronic disease
  • if ferritin is normal, this still could reflect Fe deficiency
  1. We can check transferrin
  • in Fe deficiency, transferrin increases
  • therefore there is low transferrin saturation
  • if you have chronic disease, you struggle to make proteins therefore transferrin is low/normal
43
Q

What is the problem with using ferritin in iron defiency anaemia diagnosis?

A

Ferritin is:

  • LOW in iron deficiency
  • HIGH in chronic disease

Problem with ferritin:

  • if ferritin is NORMAL, patient may be Fe deficiency if they have underlying chronic disease

For example, if a patient has rheumatoid arthritis plus a bleeding ulcer, the RhA shoves the ferritin up and ferritin appears normal

44
Q

How would you investigate and eventually form a diagnosis for the patient with the attached profile?

A

60 year-old woman

Low:

  • haemoglobin
  • MCV
  • serum iron
  • ferritin
  • transferrin saturation.

The patient is anaemic (low Hb), the serum iron is low but ferritin is low so the patient must have iron deficiency. The transferrin saturation in low, confirming Fe deficiency.

Past 60, so patient will not be menstruating. Look for another cause of iron deficiency.

Further investigations for this patient:

  • Endoscopy and colonoscopy
  • Duodenal biopsy – to be absolutely sure about coeliac disease
  • Anti-helicobacter antibodies
  • Anti-coeliac antibodies (abdominal ultrasound to look at kidneys, urine dipstick)

NOTE: Any male patient of any age with a low ferritin – this suggests iron deficiency. The patient needs to have upper and lower GI endoscopies to look for a source of bleeding.

45
Q

Outline classical presentation of anaemia due to iron deficiency

A

The haemoglobin, MCV, serum iron and ferritin would be low.

Transferrin would be high, and therefore transferrin saturation would be low.

46
Q

Outline classical presentation of Anaemia of Chronic Disease (ACD)

A

The haemoglobin and serum iron would be low.

The MCV would be normal or low.

The ferritin would be normal or high.

Transferrin would be normal or low

Transferrin saturation would be normal.

47
Q

Outline the classical presentation of Thalassemia Trait

A

The haemoglobin and MCV would be low.

However, serum iron, ferritin, transferrin and transferrin saturation would all be normal.

This can be confirmed using haemoglobin electrophoresis.

48
Q

Outline the classical presentation of rheumatoid arthritis with a bleeding ulcer

A

The haemoglobin, MCV, serum iron and transferrin saturation are low.

The ferritin is normal.

49
Q

What additional test/investigation can be done when the cause of anaemia is still unknown after looking at laboratory parameters?

A

In real life, we do not know the cause of anaemia. Sometimes, the iron parameters are unhelpful.

Additional tests include looking at the blood film (small, pale, strand shapes including pencil cells) and bone marrow.

50
Q

What does the blood film of a patient with iron deficiency look like?

A

Blood film in iron deficiency

  • Cells are very pale – they are not easy to see because they don’t have much haemoglobin
  • Red cells are normally round – pencil cells can be seen (long and thin)
  • If pencil cells are seen, the patient has iron deficiency

Yr 2 MCD - Haem (12 decks)

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