Hereditary spherocytosis

Late complications may result in the development of pigmented gallstones, which is secondary to the detritus of the broken-down blood cells (unconjugated or indirect bilirubin) accumulating within the gallbladder.

[3][4] In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms – a hemolytic crisis.

Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing for normal hemoglobin, reticulocyte and bilirubin levels.

[6] While HS is most commonly (though not exclusively) found in Northern European and Japanese families, an estimated 25% of cases are due to spontaneous mutations.

These dominant forms tend to leave a family history that yields generational splenectomies and black gallstones cholelithiasis.

[citation needed] Spherocytes have less plasma membrane compliance and fluidity, and this has implications throughout the entirety of circulation within the body, i.e. arteries, arterioles, capillaries, venules, veins, and organs.

However, the most pronounced issues with the lack of compliance and fluidity declare themselves in the failure of the erythrocyte to deform itself when transiting arterioles, capillary beds, and venules.

At the anatomic level, the passage from the cords of Billroth into the sinusoids may be seen as a "bottleneck", where red blood cells need to be flexible in order to pass through.

In HS, the erythrocytes fail to pass through fenestrations, and this is where resident splenic macrophages sample, or "bite", part of the stuck spherocytes' plasma membranes.

Available lab testing that may aid in the diagnosis of HS is as follows: The common findings of lab testing in setting of a patient with hereditary spherocytosis: In chronic cases, patients who have taken iron supplementation, have heterozygous hemochromatosis, or received numerous blood transfusions, iron overload may cause additional health issues.

Measuring iron stores is sometimes considered part of the diagnostic approach to hereditary spherocytosis in older patients presenting with heart muscle damage of unknown etiology or liver disease without apparent cause.

[6] Common current management focuses on interventions prevent the body from inappropriately destroying the functional spherocytes produced by erythrocyte progenitor cells within the bone marrow.

HS Alpha-1 deficiency.
Caption: The deficiency of alpha-1 subunits in spectrin protein network (top). The resulting failed or weakened tethering of spectrin interior to the plasma membrane to the greater actin cytoskeleton (bottom).
Micrograph of a spherocyte (center).
HS Beta deficiency.
Caption: The deficiency of Beta subunits in spectrin protein network (top). The resulting failed or weakened tethering of spectrin interior to the plasma membrane to the greater actin cytoskeleton (bottom).
HS Ankyrin deficiency.
Caption: The deficiency of ankyrin that normally associates with plasma membrane proteins (top). The resulting failed or weakened anchorage of spectin to interior plasma membrane, and subsequently weakened association between the greater actin cytoskeleton and the plasma membrane (bottom).
HS Band-3 deficiency.
Caption: The deficiency of band-3 protein (top). The resulting destabilized plasma membrane without integral band-3 PROTEIN for association with protein-4.2 and subsequently ANKYRIN (bottom).
HS Protein-4.2 deficiency.
Caption: The deficiency of protein-4.2 (top). The resulting inability of the greater actin cytoskeleton to associate with the plasma membrane via spectrin and ankyrin, and the subsequent loss of band-3 protein within microvesicles (bottom).