X-Linked autosomal recessive disorder Impairment of uroporphyrinogen synthase Hydroxymethylbilane accumulates (ferocious pink) Profound skin lesions and disfigurement Only girls get it
Porphyria Cutanea Tarda
Autosomal dominant disorder Impairment of uroporphyrinogen decarboxylase Neural and skin problems. Uroporphyrinogen accumulates Extreme photosensitivity
Autosomal dominant disorder Impairment of coproporphyrinogen oxidase Mild neural and skin problems Coproporphyrinogen accumulates Photosensitivity (erythema, bullae milia)
Autosomal dominant Slow heme turnover due to slow ferrochelatase Protoporphyrin IX accumulates Mostly dermal effects. Photosensitivity, itching, redness, painful erosions.
binds copper; appears to be more important as copper storage pool than as a transport protein; integrates iron and copper homeostasis
binds extracopuscular hemoglobin
main regulator of iron transport as an inhibitor. Low levels lead to iron absorption and transport out of cell Increased expression lead to decrease iron absorption and release from cell. It binds to ferroportin and does not let iron release from the cell.
erythropoietin and hypoxia
these molecules decrease the expression of hepcidin leading to increse iron transport out of cell
HJV, HFE, TtR2
mutations in these will lead to too little hepcidin expressed causing too much iron to be absorbed.
Iron deficiency anemia (IDA)
Caused by inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in the urine. Treated with diet, oral ferrous iron salts coupled with vitamin C. Fatigue from effect on hemoglobin, TCA, and ETC heme and iron-sulfur proteins.
the primary organ that accumulates iron.
increased iron deposition in tissues from iron overload
tissue damage from excess iron
iron intoxication signs
vomiting, severe gastroenteritis, melena, hematemesis
Autosomal recessive Mutations in the HFE gene, typically C282Y homozygotes. No mechanism for excretion of iron. Advanced symptoms include Hepatomegaly, skin bronzing, diabetes mellitus (bronze diabetes), severe fatigue, arthritis
main cellular storage protein for iron.
elevated serum ferritin
This can represent iron overload but can reflect inflammation, several types of liver damage, renal disease.
decreased serum ferritin
associated with iron deficiency and hemodialysis
iron over load treatments
phlebotomy chelation therapy Avoid red-meat and alcohol avoid vitamin C supplemetns or iron supplements.
Serum Iron (SI)
measures iron concentration in serum, i.e. outside of RBC
Serum Ferritin (SF)
measure of iron contained or stored in the body
Total Iron Binding Capacity (TIBC)
determines the capacity of circulating transferrin
Transferrin-iron saturation percentage (TS%)
how much of the transferrin is actually carrying iron. Normally 25-35%. Higher is suggestive of hemochromatosis. Lower is suggestive of iron deficiency anemia.
Monogenic, autosomal recessive condition involving liver sirrhosis pluss neurological and psychiatric defects. Defects in ATP7B protein blocks copper elimination leads to Cu accumulation.
carries most copper in human plasma. Low serum concentrations in patients with Menkes and Wilson's disease.
Menkes (kinky hair syndrome)
ATP7A defect X-Linked Plasma [catechol] are abnormal due to Cu deficiency. Low serum copper and ceruloplasmin Suspected in males who develop hypotonia, failure to thrive, and seizures between 6-10 weeks. Hair and skin changes, neurodevelopmental delays, temperature instability, hypoglycemia. Death usually by 3.
produced by the ETC. Cannot diffuse from site of origin Generates other reactive oxygen species
not a free radical but can generat free radicals by reaction with transition metals. Can diffuse through membranes
the most reactive species in attacking biologic molecules. Produced from hydrogen peroxide in the fenton reaction in the presence of Cu or Fe.
Reactive nitrogen oxygen species. A free radical that is produced endogenously by nitric oxide synthase. Binds to metal ions. Combines with O2 or other oxygen containing radicals to produce additional RNOS.