Wednesday, March 20, 2019

Anaemia: General Concepts and Iron

Just going to skip a bit ahead because we have a tute on anaemia this afternoon :)

Definition of anaemia

Anaemia is when haemoglobin levels are lower than would be expected for that individual (based on characteristics such as age and sex). There is usually a reduction in red cell count and haematocrit. Anaemia is not a disease in its own right but rather a manifestation of some other underlying problem that needs to be diagnosed.

Clinical manifestations of anaemia: symptoms, signs and classification on MCV

Since haemoglobin carries oxygen, and we kind of need oxygen to make our cells work, the lack of haemoglobin seen in anaemia can lead to tiredness, shortness of breath, dizziness, and many other fun symptoms. Signs can include pallor (especially of mucous membranes) and tachycardia (the body tries to increase cardiac output to make up for the low oxygen in the blood). Specific types of anaemia may also have specific symptoms: for instance, jaundice might be seen in either haemolytic or megaloblastic anaemia.

Causes of anaemia: principles

The main causes of anaemia are reduced production of red blood cells and increased loss of red blood cells (perhaps due to bleeding or haemolysis of red blood cells). Remember, anaemia is not a disease in its own right and the underlying cause does need to be diagnosed.

Investigations usually start by doing a blood count to see how many cells there are and how big they are, and if any abnormalities are detected, from looking at a blood film. As well as looking at red blood cells, it might also be useful to look at the other types of cells. For instance, in aplastic anaemia, the bone marrow has failed, so there will be reduced production of all types of cells in the blood. On the other hand, in pure red cell aplasia, there will only be reduced production of red blood cells. Other causes of anaemia, such as myelodysplasia (bone marrow dysfunction), or secondary causes such as insufficient nutrition (especially with iron, B12, and folate), may also lead to their own pattern of cell abnormalities.

As mentioned earlier, specific types of anaemia may also have specific symptoms. These symptoms can be used to help narrow down the cause of anaemia. For instance, since red blood cells are broken down in the spleen, splenomegaly (a large spleen) may be seen in haemolytic anaemia.

Iron metabolism and iron deficiency

Iron is important for making haemoglobin, as each haem unit is associated with iron. We normally have around 4-5g of iron, and over half of that is found in red blood cells. Once iron is absorbed, it is bound to transferrin and transported to the bone marrow. Excess iron may be stored in liver macrophages as ferritin.

Iron deficiency is due to either reduced intake of iron or increased usage of iron. Reduced intake may be due to insufficient consumption (rare in the developed world) or poor absorption (perhaps due to a condition such as coeliac disease). Increased usage may be due to chronic blood loss (due to a bleeding ulcer or perhaps heavy periods) or increased usage in general (iron requirements increase quite a bit during pregnancy).

The main causes of iron deficiency vary according to age. In very young children (<5 years), inadequate iron in the diet is the main cause of deficiency. In children aged 5-15 years old, the increased usage due to growth is the main cause. For 15-40 year olds, the main causes vary according to sex: for women, menstruation and pregnancy are the main culprits, but since men don't menstruate or get pregnant, their main cause of deficiency is coeliac disease. Finally, in people over 40 years of age, the main cause of iron deficiency is gastrointestinal blood loss (presumably due to an ulcer or something similar).

Iron deficiency anaemia is a gradual process. It starts off with negative iron balance (i.e. more usage than intake). At this stage, there is no anaemia. In the next stage, in iron deficient erythropoiesis, the red blood cells that are being produced may have lower iron, but this is still not enough to cause anaemia. Eventually, if the iron imbalance is not corrected, full-blown iron deficient anaemia can result.

In iron deficient anaemia, most red cell indices (haemoglobin levels, haematocrit, mean cell volume, etc.) are low. The main exception is the red blood cell distribution width (RDW), which might be high. This is because older red blood cells that were created prior to the deficiency might be normal, whereas the newer red blood cells are abnormal. Abnormal iron deficient cells tend to be smaller (microcytic) and hypochromic (pale). Sometimes there might be mild thrombocytosis (increased platelets) and a reduced reticulocyte count (suggesting that not as many new blood cells are being made). Iron levels can be measured directly: iron tends to be low, transferrin tends to be increased (as the body is trying to make sure that it carries and transports as much iron that it can get its hands on), transferrin saturation is low, and ferritin is low.

Other clinical features that might be seen in iron deficient anaemia are atrophic glossitis (smooth tongue), angular chelitis (redness and fissures at the corner of the mouth), and koilonychia ("spoon nails"), but these visible features are uncommon.

To treat iron deficiency, the underlying cause should be treated. If the person is not taking in enough iron, they should adjust their diet to increase their iron intake. If they are bleeding from an ulcer, the ulcer should be treated. In the interim, patients can also be given iron replacement tablets or syrup (or maybe injections if severe) to top up their iron levels.

Iron overload

Iron overload is, well, an overload of iron. Serum iron, transferrin saturation, and ferritin are all increased. There may also be abnormal liver and endocrine function as excess iron can form damaging haemosiderin deposits. Patients with genetic haemochromatosis can undergo regular venesection (basically bloodletting, but more modern) to get rid of the excess iron. Patients who have iron overload due to having blood transfusions can undergo chelation therapy to get rid of the excess iron.

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