When iron is released into the cytoplasm, it enters a cellular compartment called “labile iron pool” (LIP). Both ferrous (Fe²⁺) and ferric (Fe³⁺) iron forms are poorly bound with proteins and are highly toxic to the cells within this compartment. The unneeded iron from LIP is stored in the form of ferritin, which is organic and nontoxic. When the LIP iron content exceeds the ferritin capacity, hemosiderin is generated from ferritin denaturation. Iron in the form of hemosiderin is thought to be more toxic to the body tissues. Hemosiderin initially accumulates in the reticuloendothelial system (spleen, bone marrow, and Kupffer cells in the liver). When the reticuloendothelial system is saturated, deposition occurs in normal body tissues such as the hepatocytes, heart muscles, and the endocrine system. Chelation therapy (e.g., desferrioxamine) removes mainly the extracellular iron and only a fraction of the intracellular LIP iron.

Hemosideroses have different body manifestations according to the area of deposition:

In hemochromatosis, iron deposition initially occurs in the hepatocytes and spares Kupffer cells (the reverse situation to hemosiderosis). The age of presentation is usually between 50 and 60 years of age. Menstruation blood loss in women has a protective effect against hemochromatosis due to iron loss.

Hemochromatosis is asymptomatic in early stages. As the iron deposition progresses, liver failure, skin hyperpigmentation, arthropathy (especially in the metacarpophalangeal joints), and cardiac failure may occur. Deposition of hemosiderin in the subcutaneous tissues results in increased skin tanning and darkening.

Diagnosis is confirmed by measuring serum ferritin level, transferrin saturation testing, liver biopsy, genetic testing, and MRI.

β-thalassemia major is a hereditary hemolytic anemia, characterized by deficiency in the hemoglobin beta chain synthesis. Patients with β-thalassemia major are prone to repeated attacks of intravascular hemolysis that requires repeated hospitalization and blood transfusions.

Patients with β-thalassemia major present with microcytic hypochromic anemia with signs of fatigue and cardiac tachycardia.

Extramedullary hematopoiesis is commonly observed in these patients due to increased body demands. Extramedullary hematopoiesis can be appreciated on plain radiographs as abnormally widened, flat bones.

Within the past few years, MRI has emerged as a powerful diagnostic tool to detect hemosiderosis through the body. Techniques for tissue iron burden quantification are well established for the liver and the heart. Early treatment with chelating agents (e.g., desferrioxamine) reduces the severity of the iron burden complication. MRI iron burden quantification helps in monitoring chelation therapy.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder, characterized by episodic attacks of hemolytic anemia and vaso-occlusive attacks due to “sickling” of the red blood cells (RBCs) under certain body conditions that include dehydration, metabolic acidosis, and low oxygen saturation.

SCD results from abnormal production of hemoglobin (Hb-S). Sickle cell patients are homozygous (HbSS), while heterozygous patients have “sickle cell trait.” SCD can also arise when Hb-S is combined with abnormal hemoglobin (e.g., Hb-S-thalassemia). Hb-S differs from the normal Hb-A only in the substitution of valine for glutamic acid in the sixth position of the β chain.

In SCD, the normal, discoid RBCs shape is transformed into a sickle-shaped, sticky mass during deoxygenation. These sickle cells can stick together, forming a hard mass that may lead to embolization and arterial infarction in different parts of the body.

Approximately 50 % of patients with SCD experience painful crises by the age of 5 years. Patients with sickle cell disease have natural protection against malaria; the reasons are unknown.

Pernicious anemia (PA) is a disease characterized by the development of megaloblastic anemia due to destruction of the gastric parietal cells. Megaloblastic anemias are a subgroup of macrocystic anemias (large volume red blood cells), which most commonly arise due to vitamin B₁₂ and folate deficiencies.

Normally, the parietal cells in the gastric mucosa secrete an intrinsic factor, which is important for absorption of vitamin B₁₂ from the gastrointestinal tract. The fundus of the stomach contains parietal cells, the body contains the cells responsible for the secretion of pepsin and hydrochloric acid, and the antrum contains G cells. Patients with PA develop antigastric parietal cells (GPC) and anti-intrinsic factor antibodies (gastric parietal cells antibodies, or AGPA), which attack the parietal cells and cause autoimmune gastritis. Destruction of the gastric parietal cells leads to gastric mucosal atrophy and compromises the production of the intrinsic factor. Moreover, the atrophic gastritis also compromises the gastric acid pump, leading to deficiency in the secretion of gastric acids (hypo- or achlorhydria). Loss of vitamin B₁₂ causes defective synthesis of the bone marrow cellular activities, leading to the development of megaloblastic erythropoiesis and macrocytic anemia.

Chronic gastritis induces enterochromaffin-like cell hyperplasia, which may result in the development of gastric carcinoid tumors. Compared to the general population, gastric adenocarcinoma is 3–5 times more frequent among patients with PA. The activity of natural killer cells, which participate in immunosurveillance against tumor dissemination, is believed to be compromised in patients with PA.

Atrophic gastritis is divided into two types. Atrophic gastritis type (a) is characterized by mucosal atrophy affecting the fundus and the body of the stomach, with antral sparing. In contrast, atrophic gastritis type (b) is characterized by antral mucosal atrophy, with limited involvement of the fundus and body.

AGPAs are found in 20 % of patients with diabetes mellitus type 1 (DMT1). Researchers suggest that patients with DMT1 should be regularly screened for atrophic gastritis. PA is rare found in the general population, with an incidence of 0.1–2 % of the population. On the other hand, patients with DMT1 have a threefold increased incidence of PA, with a prevalence of 2.5–4 %.

Diagnosis is confirmed by detecting AGPA levels in the serum by the Schilling test.

Hemophilia is a rare, chronic X-linked genetic disease, characterized by the body’s inability to form clotting factors necessary for the blood clotting cascade to occur, resulting in a tendency toward spontaneous bleeding or bleeding after minor body trauma.

The word hemo means bleeding, and the word philia means tendency toward something. Patients with hemophilia have a tendency for slow bleeding, at a constant rate and without clotting, into muscles, joint spaces, and body cavities.

Blood clotting is a complicated process that involves three primary steps. The first step involves immediate constriction of the blood vessels in the area of injury. The second step involves the formation of a platelet plug that stops the bleeding. The third step involves the activation of 12 clotting factors (identified by Roman numerals) that transform the platelet plug into a more stable clot by transforming it into fibrin. The activation of clotting factors is referred to as the “clotting cascade,” because each factor stimulates the next factor in the series, until the formation of the fibrin. Deficiency of one factor will stop the cascade, and a stable clot will not form.

There are three types of hemophilia:

Internal bleeding can be seen as skin bruising, nose bleeding, or blood in the urine (hematuria). Moderate hemophiliacs may bleed 5–6 times per year. Severe hemophiliacs may have 2–3 bleeding episodes per month.

Intracranial bleeding may occur within the brain parenchyma or within the subarachnoid space. Altered consciousness, headache, nausea, and vomiting in a patient with hemophilia after a minor head injury should be considered intracranial bleeding and investigated with a head CT without delay.

Myositis ossificans (MO), also known as “Sterner’s tumor,” is a rare, nonneoplastic condition characterized by formation of bone within muscles. The disease may be hereditary (fibrodysplasia ossificans progressiva, Munchmeyer disease), nontraumatic (e.g., in hemophilia), or traumatic, which is the most common form (e.g., after muscle trauma). The previous classification is applied to intramuscular MO; however, MO can arise against a bone (parosteal MO) or evolve as periostitis (periosteoma).

In the early stages of MO, there are richly vascularized fibroblastic cell proliferations with prominent mitotic activity that mimic malignancy (early pseudosarcomatous phase). As the cells mature, the lesion typically shows three distinct zones. The first zone is composed of rapidly proliferating fibroblasts with areas of hemorrhage and necrosis; the intermediate layer is composed of osteoblasts with osteoid matrix with islands of endochondral ossification; the third outer zone is composed of mature bone, separated from the surrounded tissue by myxoid-fibrous tissue. The peripheral zone usually calcifies at 6–8 weeks after lesion initiation, and complete lesion ossification can be seen 5–6 months from the onset of symptoms. Up to 30 % of lesions regress and resolve spontaneously with maturation.

Patients with MO typically present with painful swelling, commonly in the lower limbs (60–75 % of cases). Patients, especially children, may not recall the incidence of trauma. Diagnostic imaging approach for a patient with painful swelling, with suspicion of MO, should start with conventional radiography, US, CT, and later MRI, as the MRI appearance of MO is generally nonspecific unless the lesion starts to mature. History of trauma is important to suspect MO; however, the absence of history of trauma does not exclude it.