Lecture 7: Iron Chemistry Flashcards
Where is ferritin stored?
instestinal epithelia
How is Fe3+ transported
Bound to transferrin
Iron homostasis:
cellular uptake:
Storage:
Depletion:
average daily diet contains about 10 to 15mg of iron mainly in the form of the haemo of red meats.
Uptake of iron in the small instestine: FE2+- free bound to to haem
occurs mainly in the duodenum where the ferric iron is reduced to ferrous by intestinal agents.
absorbed ferrous iron is oxidised to the ferric form iron combines with the protein apoferritin
Transient storage as ferritin inside the instestinal epithelia
- Transport in blood: FE3+- bound to transferrin in very high affinity
- Cellular uptake: endocytosis of trasnferrin, release of iron in acidic endosome
- Storage: intracellular ferritin particles
- Depletion: scaled off cells, blood loss, breast milk
Draw the cellular uptake diagram
Lecture slide
What cells and proteins are involved in iron homeostasis
Enterocytes of the proximal small intestine absorb iron
Circulating iron transferrin is taken up by erythrocyte precursors in the bone marrow,
where the iron is incorporated into the heme component of haemoglobin
Hepcidin, the iron-regulatory protein produced by hepatocytes, controls the flow of iron into the plasma
Iron stores are sensed by hepatic sinusoidal endothelial cells, which produce BMP6, a key endogenous regulator of hepcidin expression.
Assessing iron status
Serum iron: measures the level of iron in the liquid part of your blood.
Ferritin: Stored iron in the body
Transferrin or total iron binding capacity:
Transferrin is the main transport protein of iron.
TIBC is a good indirect measurement of transferrin.
Your body makes transferrin in relationship to your need for iron; when iron stores are low, transferrin levels increase, while transferrin is low when there is too much iron.
Transferrin saturation: represents the percentage of transferrin that is saturated with iron.
Souble trasnferrin receptor: Transferrin receptors are present on cell surfaces and are responsible for the internalisation of transferrin resulting in intracellular release or iron.
The amount of soluble transferrin receptor closely reflects iron stores
Disorders of iron metabolism: Iron overload due to what other complications?
Iron overload:
Is the accumulation of excess iron in body tissues.
Iron overload usually occurs as a result of a genetic predisposition to absorb iron in excess of normal.
Iron overload can also occur as a complication of
Other hematologic disorders
Chronic transfusion therapy
Chronic hepatitis.
Excessive iron ingestion.
What are two ways which cause disorder of iron metabolism
Once iron is absorbed, there is no physiologic mechanism for excretion of excess iron from the body other than blood loss (i.e., pregnancy, menstruation or other bleeding.)
When iron absorption exceeds the storage capacity of ferritin molecules, unbound iron may promote free-radical formation in cells, resulting in membrane lipid peroxidation and cellular injury
What is haemochromatosis and causes
Hemochromatosis is a disease that occurs as a result of significant iron overload.
Genetic (HFE gene mutation) or non genetic causes
Effects of haemochromatosis
Accumulates where?
Symptoms?
Excess iron accumulates in organs (particularly the liver, pancreas,
heart), joints, and the pituitary gland.
After several decades of increased iron absorption non-specific symptoms (i.e., fatigue, weakness, joint stiffness) develop, followed by advanced conditions (i.e., arthritis, cirrhosis, liver cancer).
HFE gene mutations codes for what? AND how does this relate to iron overload?
codes for a transmembrane glycoprotein that modulates iron uptake. This protein is highly expressed in intestinal cells at the site of dietary iron absorption.
HFE protein is bound to transferrin receptor and when bound prevents iron from being absorbed and modulates iron absorption. If there is a mutation and the HFE protein is not coded for and thus not present, this allows the transferrin receptor to absorb as much iron that comes to it.
Recent studies suggest that loss of a functional HFE protein leads to increased iron uptake in the intestinal epithelial cell, which results in increased dietary iron absorption.
HFE protein stops iron absorption, makes hepcidin (stop iron export) SO aim is to increase ferritin stores
What is herditary haemochromatosis
Hereditary hemochromatosis is the genetic disease that results
from significant iron overload.
The majority of hereditary hemochromatosis (also known as Type 1 Hemochromatosis) is associated with homozygous mutations in the HFE gene.
Clinical aspects of haemochromatosis (what is tests are elevated)
elevated transferrin saturation,
elevated serum ferritin,
elevated transaminase (indicative of liver disease), or
elevated blood glucose (indicative of diabetes)
Tests confirming haemochromatosis
A. Indirectly by quantitative phlebotomy.
The amount of mobilizable iron removed from the body by weekly or biweekly phlebotomy measures the degree of iron overload and confirming a hemochromatosis diagnosis
B. HFE genotyping.
Genotyping for HFE mutations can provide additional confirmatory evidence that a patient has hereditary hemochromatosis.
Causes of Iron Defiency Anaemia
Diets low in iron
Body changes
An increased iron requirement and increased red blood cell production is required when the body is going through changes such as growth spurts or pregnancy.
Gastrointestinal tract abnormalities
Malabsorption of iron is common after some forms of gastrointestinal surgeries. Most of the iron taken in by foods is absorbed in the upper small intestine. Any abnormalities in the gastrointestinal (GI) tract could alter iron absorption and result in iron-deficiency anemia.
