Pathophysiology

Normal Physiology of Iron in the body:

  1. Iron enters the body through the diet in two forms, heme and non-heme iron
    • Both forms are found in foods of plant and animal origin
    • Not much is known about the absorption of heme iron, which is mostly consumed through foods of animal origin2.Non-heme iron enters the proximal part of the small intestine, called the duodenum, and is absorbed by mature duodenal enterocytes
  3. If iron is not immediately needed by the body, it is stored within the cells by ferritin, the major iron-storing protein
    • If the body does not end up needing this iron, it is lost through the death of the enterocyte
  4. If the iron is immediately needed, it must move from the intestinal lumen into the bloodstream
    • This is accomplished by dietary iron (Fe3+) first being reduced to ferrous iron (Fe2+) by duodenal cytochrome B
  5. Next, divalent metal transporters (DMT1) help the Fe2+ cross the apical brush-border of the enterocyte
  6. Ferroportin (FPN1) then steps in to export the iron across the enterocyte basolateral membrane to the bloodstream where it is converted back into iron (Fe3+) to be used in the body
    • Newly absorbed or released iron binds to plasma transferrin which distributes the iron around the body
    • The place of most need is erythroid marrow where iron is utilized for hemoglobin synthesis in the making of new RBCs
  7. Recycling of iron occurs when macrophages eat up RBCs, releasing the iron back into circulation either to be stored or used again
  8. Iron homeostasis is controlled by Hepcidin which is released by the liver
    • If iron requirements increase, hepcidin levels decrease and more iron is mobilized from storage or absorbed in the duodenum
    • Alternatively, if there are adequate levels of iron hepcidin levels increase to downregulate these processes
  9. Iron’s function in the body
    • RBC formation, immune function, brain function, muscle function, and energy production

(Anderson & Frazer, 2017)

Retrieved from https://academic.oup.com/view-large/figure/109555107/ajcn155804fig1.tif

Pathophysiology of Iron Deficiency Anemia (IDA):

Pathophysiology:

  • IDA is a hypochromic-microcytic anemia – red blood cells (RBCs) are abnormally small with low levels of hemoglobin (hgb)
  • Despite the cause, IDA occurs when the body’s iron demand exceeds that of it’s supply
  • Two types: iron store depletion vs. metabolic/functional
  • Inflammatory response of body in response to infection may also contribute to an acute form of IDA
  • How quickly IDA develops depends on cause, but develops in three stages

Iron Store Depletion:

  1. Inadequate dietary intake
    1. Diets low in meat, fish, beans, or iron-fortified foods – commonly seen with vegetarians or individuals living in poverty
    2. Mechanism – low iron stores leads to demand > supply
  2. Excessive blood loss
    1. Hemorrhage, menorrhagia (heavy menstrual bleeding)
    2. Mechanism – depleting iron stores faster than replacing combined while increasing body’s demand for iron

Metabolic/Functional:

  1. Insufficient iron delivery to bone marrow
    1. Iron stores adequate to meet body’s need
    2. Mechanism – delivery to bone marrow to be utilized in the production of RBCs is impaired
  2. Impaired use of iron within bone marrow
    1. Iron stores adequate to meet body’s need
    2. Mechanism – even when delivered, there is impaired use of iron in the bone marrow to produce RBCs

Inflammatory Response:

  • Iron regulates immune effector mechanisms – cytokine activity, nitric oxide formation, and T-cell proliferation
  • Acquired IDA may be body’s response to a pathogen – many pathogens require iron to survive

Stages of Development:

  1. Body’s iron stores are depleted, RBC production proceeds normally with hemoglobin content remaining normal
  2. Reduction in iron transport to bone marrow, causing iron-deficient RBC production (hemoglobin content of RBC is reduced)
  3. Small, hemoglobin-deficient cells enter circulation, replacing normal RBC

(McCance & Rote, 2019)

Clinical Presentation:

  • Early symptoms of IDA include fatigue, weakness, shortness of breath, and pallor
    • These symptoms start to develop in stage three of development due to the reduction in hemoglobin contributing to hypoxemia
  • As hemoglobin levels continue to drop, epithelial tissue begins to express structural and functional changes such as brittle, thin, ridged and spoon-shaped finger nails (figure 1)
    • These changes are a result of impaired capillary circulation
  • Glossitis (figure 2)
    • Caused by tongue papillae atrophy
    • Leads to soreness and redness of the tongue
  • Additionally, individuals with IDA experience angular stomatitis, a dry soreness in the epithelial tissues at the corners of the mouth
  • Iron is an essential component of many enzymes in the body (cytochromes, myoglobin, catalases, peroxidases)
    • Individuals with IDA can also experience gastritis, neuromuscular changes, irritability, headaches, numbness, tingling, and vasomotor disturbances due to deficiencies in these iron-dependent enzymes

(McCance & Rote, 2019)

 

 

Figure 1: 

From Hoffbrand AV, Pettit JE, Vyas P: Color atlas of clinical hematology, ed 4, London, 2009, Mosby

Figure 2:

From Hoffbrand AV, Pettit JE, Vyas P: Color atlas of clincal hematology, ed 4, London, 2009, Mosby

Diagnosis Criteria:

Evaluation of IDA is based on clinical symptoms and blood tests.

  • Low hgb levels in the blood
    • Caused by the direct reduction of hemoglobin synthesis due to low levels of iron or impaired RBC production
  • Lower than normal serum iron, ferritin, and transferrin saturation levels
    • Ferritin – iron-storing protein
    • Transferrin – distributes iron around the body
    • If these levels are low, indicated there is less iron being stored and transferred in the body
  • Iron store levels will be low
    • Directly measured by bone marrow biopsy
    • Indirectly by serum ferritin level, transferrin saturation levels, or total iron-binding capacity

(McCance & Rote, 2019)