The polypeptide hepcidin, which is primarily formed in the liver and excreted via the kidneys (Nemeth 2014), inhibits the ability of the intestine to absorb iron. In chronic inflammation, it is increased by inflammatory toxins, especially interleukin. In addition, iron absorption by duodenal enterocytes is downregulated. Thus, a state of functional iron deficiency develops (Cullis 2013).
Erythropoietin (EPO) produced in the kidney promotes the formation of erythrocytes. In inflammatory anemia, the increase in EPO that normally follows a drop in Hb- levels is attenuated (Cullis 2013).
In chronic inflammation, endogenous EPO- production is too low because the bone marrow responds inadequately to stimulation (Kasper 2015).
Fränkel (2017) points to recent studies showing that ACD can be caused by both impaired erythropoiesis and iron sequestration. Proinflammatory cytokines released by inflammation suppress erythropoiesis and cause iron sequestration by the hormone hepcidin. In addition, changes in the cell membrane shorten erythrocyte survival.
In summary, the following factors play a role in ACD:
- 1. slightly shortened erythrocyte survival due to destruction of the cell wall.
- 2. occurrence of hypoferremia due to limited uptake of iron during erythropoiesis due to cytokine stimulation of hepcidin.
- 3. suppression of erythropoiesis by direct action of cytokines on bone marrow.
- 4. effects of inflammation on erythropoietin production are variable (Nemeth 2014).
- Decrease in hemoglobin levels:
Fever and cytokines released during infection exert selective pressure on the erythrocyte membrane, resulting in rupture of the membrane (Kasper 2015).
- Chronic renal failure:
Anemia occurring in chronic renal failure represents a multifactorial process:
- deficient production of erythropoietin in the peritubular cells of the kidneys
- resulting defective erythropoiesis
- impairment of iron utilization
- stimulation of hepcidin production
- Loss of iron through hemodialysis (on average 1 - 3 g / year)
- Occurrence of hyperparathyroidism
- Deficiency of essential nutrients such as folic acid, iron, vit. B
- uremic toxins
- Medications such as ACE inhibitors
- V. a. a peripheral resistance to EPO (Gluba- Brzozka 2020)
- Positive effects of anemia:
Decreased available iron blocks the growth of invading pathogens. In addition, the deprivation of iron leads to a strengthening of the immune defense mechanisms of macrophages (Weiss 2009).