Iron Deficiency and Anaemia of Chronic Disease Flashcards
In what state is the iron in the haem group of haemoglobin?
Fe2+ (ferrous)
How much iron do you need per day to maintain the production of red blood cells?
20 mg/day
How can iron be lost under normal, non-pathological conditions?
Desquamation of cells in the skin and gut
Bleeding (menstruation is one of the largest causes of loss of iron from the body in women)
How much iron does the human diet normally provide?
12-15 mg/day
State some natural foods that are high in iron.
Meat and fish
Vegetables
Whole grain cereal
Chocolate
Which form of iron cannot be absorbed?
Fe3+ (ferric)
What effect does drinking tea have on iron absorption?
Cups of tea promotes the conversion of Fe2+ to Fe3+ so less absorbed
Why do meat and fish eaters have an advantage over vegetarians in terms of iron absorption?
They will absorb iron in the haem form
haem iron= iron has already been incorporated into a haem group so easier for u to absorb
State three systemic causes that increase iron absorption.
Iron deficiency
Anaemia/hypoxia
Pregnancy
Which channel, on the basement membrane of intestinal epithelial cells, allows movement of iron into the circulation?
Ferroportin
What is a key regulator of iron absorption that affects ferroportin?
Hepcidin
How is the level of hepcidin affected?
There are certain proteins (such as hepcidin) that have iron-responsive elements in their genes
So iron is part of the complex that switches on hepcidin transcription
High iron - high hepcidin - low ferroportin- low absorption
How is iron stored within cells?
In ferritin micelles
What transports iron in the circulation?
Transferrin
State three parameters that can be measured that involve transferrin?
Transferrin
Transferrin Saturation
Total Iron Binding Capacity (TIBC)
What is the normal transferrin saturation?
20-40%
Where is erythropoietin produced and what effect does it have?
Kidneys (stimulated by hypoxia)
Increase in red blood cell precursors
Red blood cell precursors will survive longer and the EPO will make them grow and differentiate to produce more progeny
What is anaemia of chronic disease?
Anaemia that is seen in patients with chronic disease
What typical signs of anaemia will ACD patients NOT have?
They will NOT be bleeding
They will NOT be iron deficient, B12 deficient or folate deficient
They will NOT have any bone marrow infiltration
State some laboratory signs of being ill.
Raised Erythrocyte Sedimentation Rate (ESR, raised due to RBC clumping together due to increased blood fibrinogen levels)
Acute phase response:
Raised C-reactive protein (CRP, an acute phase protein involved in complement activation during inflammation)
Raised Ferritin (cells die in inflammation and leak ferritin)
Raised Factor VIII
Raised Fibrinogen
Raised Immunoglobulins
State some causes of anaemia of chronic disease.
Chronic infections – e.g. TB/HIV
Chronic inflammation – e.g. SLE, rheumatoid arthritis
Malignancy
Miscellaneous (e.g. cardiac failure)
What is the underlying cause of ACD?
ACD is due to the cytokine release that happens when someone is unwell
The cytokines
a. They stop erythropoietin from increasing
b. Stop iron flowing out of cells and hence the utilisation of iron by RBC
c. Increase production of ferritin ie stuck as ferritin, cannot be utilised
d.Increased death of red cells
Give examples of cytokines involved in ACD.
TNF-alpha
Interleukins
State four broad causes of iron deficiency.
Bleeding
Increased use (e.g. growth, pregnancy)
Dietary deficiency (e.g. vegetarian)
Malabsorption (e.g. Coeliac disease)
In what 4 groups of patients do you perform full GI investigations given the fact that they are iron deficient but have a good diet and excluded from coeliac disease?
Male Women over 40 Post-menopausal women Women with scanty menstrual loss slide 31 for explanations Summary: Male OR any female who has reached/about to reach menopause or does not really bleed much normally
State some other investigations that can be performed.
Antibodies for coeliac disease
Check for urinary blood loss
State three causes of a low MCV.
Iron deficiency
Anaemia of chronic disease
Thalassemia trait
How would you confirm thalassemia trait?
Haemoglobin electrophoresis
How does serum iron help distinguish between the three causes of microcytic anaemia?
Iron deficiency – LOW serum iron
ACD – LOW serum iron
Thalassemia trait - NORMAL serum iron
so it rules out thalassemia trait
Describe the difference in ferritin levels in iron deficiency and anaemia of chronic disease.
Iron deficiency – LOW
ACD – HIGH (ferritin is an acute phase protein and so will rise in eg chronic infections or inflammation. Also because cytokines in ACD promote ferritin production)
Why is ferritin not always reliable? What should you do instead in these scenarios?
Some people may have a anaemia of chronic disease and be iron deficient due to bleeding e.g. rheumatoid arthritis and a bleeding ulcer. Bleeding reduces ferritin stores but cytokines from ACD blocks iron transport out of the cell and so ferritin may build up. This means that the amount of ferritin that leaks into the blood may seem normal)
You need to check the signs of infection/inflammation such as ESR and CRP to see if there is an underlying condition causing a rise in acute phase proteins
Describe the difference in transferrin in iron deficiency and ACD.
Iron deficiency – HIGH
ACD – LOW/NORMAL
Describe the difference in transferrin saturation in iron deficiency and ACD.
Iron deficiency – LOW
ACD – NORMAL
What is the diagnosis of a man of any age with a low ferritin?
Iron deficiency
He needs upper and lower GI endoscopies to look for the source of the bleeding
State what you’d expect the following parameters to be in iron deficiency:
a. Hb
b. MCV
c. Serum Iron
d. Ferritin
e. Transferrin
f. Transferrin Saturation
a. Hb - LOW
b. MCV - LOW
c. Serum Iron - LOW
d. Ferritin - LOW
e. Transferrin - HIGH
f. Transferrin Saturation - LOW
State what you’d expect the following parameters to be in anaemia of chronic disease:
a. Hb
b. MCV
c. Serum Iron
d. Ferritin
e. Transferrin
f. Transferrin Saturation
a. Hb - LOW
b. MCV - LOW/NORMAL
c. Serum Iron - LOW
d. Ferritin - HIGH/NORMAL
e. Transferrin - LOW/NORMAL
f. Transferrin Saturation - NORMAL
State what you’d expect the following parameters to be in thalassemia trait:
a. Hb
b. MCV
c. Serum Iron
d. Ferritin
e. Transferrin
f. Transferrin Saturation
a. Hb - LOW
b. MCV - LOW
c. Serum Iron - NORMAL
d. Ferritin - NORMAL
e. Transferrin - NORMAL
f. Transferrin Saturation - NORMAL
what is acute phase reaction
The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins are an integral part of the acute phase response.
