Page 262 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Hemochromatosis by Fe (Fe accelerates ascorbic acid break-
down).
Hemachromatosis is a condition in which
there is an excessive accumulation of iron (Fe) Wilson’s Disease
in the body, deposited in the parenchymal cells
of the liver, pancreas, and other organs. Pri- Copper (Cu) metabolism (→ B). Normal Cu up-
mary (= idiopathic, = hereditary) hemochro- take is ca. 2–5 mg daily, of which 40–60% are
matosis (→ A1) is a common disease (1 in absorbed in the stomach and upper duode-
400), inherited as an autosomal recessive trait. num. It is then incorporated mainly into ceru-
The abnormality consists of a markedly raised loplasmin (CP) in the liver. It reaches the sys-
intestinal absorption of Fe; in a year 0.5–1 g ex- temic plasma in this form (ca. 93% of plasma
cess Fe is taken up. Fe, ferritin, and transferrin Cu; → B1). CP, which binds six to seven Cu
saturation are increased in serum (→ p. 38). If atoms relatively firmly, is apparently impor-
diagnosed early, the increased Fe content tant for the oxidation of Fe 2+ in plasma
(25–50 g) can be normalized by means of (→ p. 38), but only a little CP-bound Cu is re-
weekly bloodlettings over one to two years (se- leased into the tissues. This is not true of the
rum ferritin < 50 µg/L; transferrin saturation portion of Cu that is bound to transcuprin and
< 50%). Secondary hemochromatoses (→ A2)
albumin (ca. 7% of plasma Cu). Old (desialysed)
Metabolism occur if there is an abnormal utilization of Fe CP is broken down in the liver and the liber-
ated Cu is excreted, firmly bound to biliary
(increased Fe absorption with ineffective
proteins (→ B2), in the bile and stool (ca.
erythropoiesis, for example, in β thalassemia
Wilson’s disease (hepatolenticular degen-
(e.g., alcoholic cirrhosis, portocaval shunt), in
8 or sideroblastic anemia; → p. 36), liver disease 1.2 mg/d).
atransferrinemia (→ p. 38), and porphyria cu- eration) is an autosomal recessive disorder of
tanea tarda (→ p. 254) as well as in excessive Cu metabolism in which the liver, central ner-
Fe supply, either orally or parenterally (fre- vous system, eyes, and other organs are over-
quent blood transfusions which are a second loaded with Cu. The imbalance is caused by ge-
cause in conditions of abnormal Fe utilization; netic defects fo the Cu-transporting Cu-ATPase.
long-term hemodialysis; injection of Fe prep- The defect results in failure to excrete suffi-
arations). cient Cu via the bile, the normal route, and
Toxic cell damage (→ A3) is the result of in- the ability to incorporate Cu into CP is dimin-
creased Fe deposition (especially in the form of ished (→ B). As a result, free or only loosely
hemosiderin [siderosis]). Participating in this bound Cu accumulates in the liver and then in
are: 1) Fe-mediated formation of O 2 radicals plasma (at subnormal total Cu concentration)
(lipid peroxidation of cellular membranes); 2) and in other organs (→ B3). In this form it is
DNA damage; and 3) an increased formation of cytotoxic because it binds to proteins, espe-
collagen, initiated by Fe. cially the sulfhydryl groups, and promotes the
When the Fe content in the liver has in- formation of O 2 radicals (lipid peroxidation).
creased to ca. 20 times the normal amount, fi- The effects (→ B4) are hemolytic anemia and
brosis with subsequent cirrhosis develops chronic active hepatitis that can later change
(→ p.172ff.). The risk of lethal hepatocellular to cirrhosis. If the hepatitis takes a fulminant
carcinoma increases twohundredfold. Pan- course, large amounts of Cu are suddenly re-
creatic fibrosis caused by siderosis results in leased from the necrotic liver and this may
insulin deficiency and thus diabetes mellitus. trigger a hemolytic crisis. The accumulation of
The incorporation of melanin and hemosiderin Cu in the CNS can cause numerous and diverse
in the skin (especially if exposed to the sun) neurological, neuromuscular, and psychogenic
leads to marked pigmentation (“bronzed dia- abnormalities. Deposition of granular Cu in
betes”). Siderosis in the heart causes a cardio- Descemet’s membrane of the eye can bring
myopathy that through arrhythmia and heart about a Kayser–Fleischer ring around the per-
failure is a frequent cause of death in young iphery of the cornea. The kidneys, skeleton,
252 patients. The joint damage (pseudogout) is in and heart can also be affected.
part due to vitamin C deficiency brought about
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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