Pathology 3500

Iron Deficiency

The Importance of Iron:

Iron is an essential mineral that plays a crucial role in several physiological processes within the body. Here’s an overview of its key functions:

1. Oxygen Transport

Iron is a key component of hemoglobin, the protein in red blood cells responsible for transporting oxygen from the lungs to tissues and organs.
Iron is also part of myoglobin, a protein that stores and supplies oxygen to muscles .

2. Enzyme Function

Iron is a cofactor for numerous enzymes, including those involved in DNA synthesis, electron transport, and neurotransmitter production.
It supports the function of cytochromes, which are necessary for energy production through cellular respiration .

3. Metabolism and Energy Production

Iron is essential for mitochondrial function because it assists with enzymes or cofactors needed for ATP (adenosine triphosphate) production, the primary energy source for cells.
It aids in the metabolism of macronutrients (carbohydrates, proteins, and fats), ensuring efficient energy use .

🩺 Symptoms:

Individuals with iron deficiency often experience a range of symptoms, many of which can impact daily functioning and overall well-being

Fatigue and Weakness

Reduced hemoglobin levels impair oxygen delivery to tissues, leading to persistent tiredness and decreased muscle strength [5] .

Pale Skin (Pallor)

A noticeable paleness, especially in the face, inner eyelids, and nails, results from decreased red blood cell production [4].

Cold Hands and Feet

Poor circulation due to reduced red blood cells can make extremities feel unusually cold [4].

Shortness of Breath

Shortness of Breath
Lower oxygen-carrying capacity causes difficulty breathing during routine activities or exercise [6] .

Brittle Nails and Hair Loss

Brittle Nails and Hair Loss
Iron deficiency can weaken nails, making them brittle, and may contribute to hair thinning or loss [7].

Headaches

Frequent headaches may occur due to reduced oxygen delivery to the brain [8] .

Chest Pain or Heart Palpitations

The heart may work harder to compensate for low oxygen levels, leading to chest discomfort or irregular heartbeats [10] .

Difficulty Concentrating ("Brain Fog")

Impaired oxygenation can affect cognitive functions, resulting in concentration difficulties [10] .

Iron Physiology: Absorption

Iron is primarily absorbed in the duodenum and proximal jejunum of the small intestine.

The absorption process depends on the source of iron: heme iron (derived from animal sources) is more efficiently absorbed than non-heme iron (derived from plant sources).

The regulation of iron absorption is controlled by hepcidin, a hormone that inhibits iron release into the bloodstream. Hepcidin accomplishes this by degrading ferroportin, the protein responsible for exporting iron from intestinal cells into circulation.

Pathophysiology

Iron deficiency occurs when the body's iron stores are depleted, leading to impaired oxygen transport and enzyme function. The condition develops in three stages:

(1) Iron depletion, where stored iron levels drop.

(2) Iron-deficient erythropoiesis, where red blood cell production is affected.

(3) Iron-deficiency anemia, where hemoglobin synthesis is significantly impaired, reducing oxygen delivery to tissues .

🔬 Diagnostic Tests for Iron Deficiency

Serum Ferritin
- Most specific test for iron stores; <30 ng/mL confirms deficiency
- Low even before anemia develops

Serum Iron
- Often reduced in iron deficiency, but fluctuates with diet and inflammation
- Best interpreted with other iron studies

Total Iron-Binding Capacity (TIBC)
- Increased as the body tries to bind more iron
- Reflects elevated transferrin levels

Complete Blood Count (CBC)
- Shows microcytic, hypochromic anemia: ↓MCV, ↓MCH, ↑RDW
- Early clue before ferritin drops

Peripheral Blood Smear
- May show pale (hypochromic), small (microcytic) RBCs
- Supports CBC findings

Secondary Complications

Iron deficiency, the most common nutritional disorder worldwide, can lead to a range of secondary complications that affect multiple organ systems and overall health.

Screen Shot 2025-04-02 at 3.35.00 PM.png

Iron Deficiency Anemia (IDA)

Immune System Dysfunction

This is the most direct complication. It occurs when iron depletion impairs hemoglobin synthesis, reducing oxygen-carrying capacity

Another secondary consequence of iron deficiency includes reduced immune cell function (e.g. an impaired T-cell response).

Plummer-Vinson Syndrome

Characterized by iron deficiency anemia, dysphagia, and esophageal webs; increases risk of upper esophageal carcinoma .

Pregnancy Complications:

Cardiovascular Impact

Restless Legs Syndrome (RLS)

A secondary consequence of iron deficiency is an Increased risk of preterm birth, low birth weight and maternal morbidity

Iron deficiency (even without anemia) impairs myocardial energetics, worsening symptoms and increasing hospitalization risk in heart failure patients

RLS causes discomfort and urges to move the legs, especially at night. Iron therapy often improves symptoms

💊 Treatment and Management

1. Dietary Modifications

Include iron-rich foods like red meat, legumes, and leafy green vegetables
Pair with Vitamin C-rich foods to boost iron absorption

2. Iron Supplementation

Oral Supplements: Ferrous sulfate is commonly used
Parenteral Iron: Recommended for individuals with absorption issues or intolerance to oral iron

3. Address Underlying Causes

Identify and treat sources of blood loss, such as gastrointestinal bleeding or heavy menstrual periods

4. Ongoing Monitoring

Regularly check ferritin and hemoglobin levels to assess treatment effectiveness

ron-Deficient-Anemia-prone-regions-revealed-low-CFR-by-COVID-19-CFR-Case-Fatality-Rate.png

Source: Pandey S, Singh V. Food Fortification to Combat Iron Deficiency Anaemia. International Journal of Advanced Nutritional and Health Science 2013;1(1): 39-47.

🌎 Global Impact

Iron deficiency is a major global health issue, particularly in developing countries, where it remains the leading cause of anemia.

Limited access to iron-rich foods, poor dietary diversity, and high rates of parasitic infections and malnutrition contribute to its widespread prevalence [17].

The most affected populations include women of reproductive age, pregnant women, and young children due to increased iron demands and frequent blood loss [17] .

Inadequate healthcare systems and lack of supplementation in high-burden regions worsen the prevalence and outcomes of IDA [18].

Multifactorial interventions (e.g., food fortification, deworming, maternal supplementation) are essential but underutilized in many high-risk settings [18].