IDA Flashcards
(40 cards)
What’s the Total Body Iron in both male & female
Adult Male: The total iron content is approximately 50 milligrams per kilogram of body weight. This means that for a 70 kg adult male, the total body iron would be around 3500 mg (or 3.5 grams).
Adult Female: The total iron content is slightly lower, at around 40 milligrams per kilogram of body weight. Thus, for a 60 kg adult female, the total body iron would be around 2400 mg (or 2.4 grams).
Iron in Hemoglobin
Hemoglobin, the protein in red blood cells that carries oxygen, contains a significant portion of the body’s iron. Specifically:
450 mL of Blood: Contains about 200 mg of iron.
Since an average adult has about 5 liters (5000 mL) of blood, this means that a substantial amount of iron is tied up in hemoglobin within red blood cells.
Stored Fe is stored in what form?
Ferritin: This is the primary storage form of iron and is found in various cells throughout the body.
Haemosiderin: This is an iron-storage complex that is less readily available for use than ferritin. It is often formed when there is excess iron.
These storage forms of Fe are primarily located in:
Macrophages of the Liver, Spleen, and Bone Marrow: Macrophages are a type of white blood cell that engulfs and digests cellular debris and pathogens. They play a crucial role in recycling iron from old red blood cells.
Liver Parenchymal Cells: These are the functional cells of the liver, involved in a wide range of metabolic processes including iron storage.
List the Proteins important in iron metabolism
Hemoglobin: A protein in red blood cells that carries oxygen from the lungs to tissues and returns carbon dioxide from tissues to the lungs. Hemoglobin contains iron within its heme group, essential for oxygen binding.
- Other haem proteins: These include myoglobin (found in muscle cells), cytochromes (involved in electron transport and energy production), and various enzymes. These proteins also contain heme groups that require iron to function.
Ferritin:
A protein that stores iron and releases it in a controlled fashion. Ferritin acts as a buffer against iron deficiency and iron overload. It is found in cells throughout the body, including the liver, spleen, and bone marrow.
Hemosiderin:
A complex of ferritin, denatured ferritin, and other materials. It is an iron-storage complex that usually forms when there is an excess of iron, particularly in conditions of iron overload.
Transferrin and transferrin receptor:
Transferrin: A blood plasma protein that binds and transports iron throughout the body. Each transferrin molecule can carry two iron ions.
Ferroportin:
A protein that transports iron from inside cells to the outside. It is found on the basolateral surface of enterocytes in the gut (where it exports absorbed iron into the bloodstream), in macrophages (where it releases recycled iron), and in hepatocytes.
Divalent metal transporter 1 (DMT1):
A protein that transports divalent metal ions, including ferrous iron (Fe²⁺), across cell membranes. It is crucial for the absorption of iron from the diet in the intestine and for the uptake of iron by cells throughout the body.
Hepcidin:
A liver-produced hormone that regulates iron balance. Hepcidin controls the amount of iron released into the bloodstream by binding to ferroportin, causing its internalization and degradation. This decreases iron absorption from the gut and iron release from macrophages.
- Hemoglobin and Other Hem Proteins
Function: Hemoglobin, found in red blood cells, carries oxygen from the lungs to the tissues and returns carbon dioxide from the tissues to the lungs. Other hem proteins include myoglobin (in muscles) and cytochromes (involved in electron transport).
Effect on Iron Levels: Hemoglobin contains the majority of the body’s iron. It does not directly affect iron levels but is crucial for the body’s use of iron.
- Ferritin
Function: Ferritin is a protein that stores iron in cells, releasing it in a controlled fashion.
Effect on Iron Levels: It regulates iron storage and release, thus playing a crucial role in maintaining iron homeostasis. Ferritin levels can indicate the amount of stored iron in the body.
- Hemosiderin
Function: Hemosiderin is an iron-storage complex, less accessible than ferritin and typically found in macrophages.
Effect on Iron Levels: It stores excess iron, especially when there is an overload. High levels can indicate iron overload in tissues.
- Transferrin and Transferrin Receptor
Function: Transferrin is a blood protein that binds and transports iron throughout the body. Transferrin receptors on cell surfaces bind to transferrin to allow iron to enter cells.
Effect on Iron Levels: Transferrin increases iron levels in the blood and facilitates iron uptake by cells. Transferrin receptor expression increases when cells need more iron.
- Ferroportin
Function: Ferroportin is a protein that exports iron from cells into the blood.
Effect on Iron Levels: It increases iron levels in the blood by transporting iron out of storage cells, like those in the liver and macrophages.
- Divalent Metal Transporter 1 (DMT1)
Function: DMT1 is involved in the uptake of iron (and other divalent metals) from the gut and into cells.
Effect on Iron Levels: It increases iron levels in cells by facilitating iron absorption from the diet and transport into cells.
- Hepcidin
Function: Hepcidin is a hormone produced by the liver that regulates iron homeostasis.
Effect on Iron Levels: Hepcidin decreases iron levels in the blood by inhibiting ferroportin, reducing iron absorption from the intestine, and trapping iron in storage sites. High hepcidin levels lead to decreased iron in the blood, while low levels increase iron availability
- Increase Iron in Blood: Transferrin, Ferroportin (by exporting iron from cells to blood)
- Increase Iron in Cells: Transferrin (by delivering iron to cells), DMT1 (by absorbing iron into cells)
- Decrease Iron in Blood: Hepcidin (by inhibiting ferroportin)
- Hormone Affecting Both Blood and Cells: Hepcidin
What’s sideroblast
Erythroblasts containing ferritin aggregates are called sideroblasts.
Utilization in Bone Marrow
In the bone marrow, erythroblasts (immature red blood cells) internalize iron to form hemoglobin (heme).
Some iron in erythroblasts is stored as ferritin. Erythroblasts containing ferritin aggregates are called sideroblasts.
Storage in Macrophages
Macrophages store iron in the form of ___ and _____, primarily derived from the breakdown of old red blood cells (senescent red cells).
When the body needs more iron, macrophages can mobilize their stored iron into the bloodstream.
ferritin & hemosiderin
Iron Loss
Iron is lost from the body through the desquamation (shedding) of intestinal cells.
What are the various Fe requirements in
adult male
Adolescent
Female of child bearing age
Pregnancy
Infant 5-12M
Infant 1-4M
Specific Requirements
Adult males and postmenopausal women: 1 mg per day.
Adolescents: Increased iron requirement due to growth.
Females of childbearing age: Increased requirement due to menstrual blood loss (3 mg per day).
Pregnancy: 3-4 mg per day.
Infants (5-12 months): 1 mg per day.
Infants (up to 4 months): 0.5 mg per day.
What are the Factors Favoring Iron Absorption?
Haem Iron
Iron from animal sources (meat, fish, poultry) is in the haem form, which is more efficiently absorbed by the body.
Ferrous Form
Iron in the ferrous (Fe²⁺) form is better absorbed compared to the ferric (Fe³⁺) form.
Acids
Hydrochloric acid (HCl): Present in the stomach, it helps convert iron to its more absorbable ferrous form.
Vitamin C (ascorbic acid): Enhances iron absorption by reducing ferric iron to ferrous iron and forming a soluble iron-ascorbate complex.
Solubilizing Agents
Sugars and amino acids: They form soluble complexes with iron, improving its absorption.
Reduced Serum Hepcidin
Lower levels of hepcidin, a hormone that inhibits iron absorption, favor increased iron absorption.
Ineffective Erythropoiesis
Conditions where red blood cell production is impaired, leading to increased iron absorption to meet the body’s needs.
Pregnancy
Increased iron requirements during pregnancy enhance iron absorption.
Hereditary Hemochromatosis
A genetic disorder that increases iron absorption regardless of the body’s iron status.
What are the Factors decreasing Iron Absorption?
Inorganic Iron
- Iron from plant sources and supplements, which is less efficiently absorbed than haem iron.
Ferric Form
- Iron in the ferric (Fe³⁺) form is less readily absorbed compared to the ferrous form.
Alkalis
- Antacids and pancreatic secretions: These can raise the pH of the stomach, reducing the conversion of ferric iron to the more absorbable ferrous form.
Precipitating Agents
- Phytates (found in grains and legumes), tea, and phosphates: These compounds can bind to iron and form insoluble complexes, reducing its absorption.
Increased Serum Hepcidin
- Higher levels of hepcidin inhibit iron absorption by blocking the release of iron from enterocytes (intestinal cells) and macrophages.
Decreased Erythropoiesis
- Reduced production of red blood cells decreases the body’s demand for iron, lowering absorption rates.
Inflammation
- Chronic inflammation can increase hepcidin levels, thus reducing iron absorption.
What’s the Location of Fe Absorption in the git
Duodenum and Upper Jejunum: These are the primary sites for iron absorption due to their optimal environment and specialized cells
What are the Forms of Iron Absorption
Ferrous Form (Fe²⁺): Iron must be in the ferrous form to be absorbed efficiently.
Haem Iron: About one-fourth of haem iron from animal sources is absorbed. After cellular uptake, haem is broken down, and iron is released into the cytoplasm.
Non-Haem Iron: Only about 1-2% of non-haem iron from plant sources is absorbed.
What are the retarding and enhancing chm/substance that affects Fe absorption
Factors Influencing Absorption
- Retarding Factors:
Tannates (found in tea),
Phytates (found in grains and legumes),
Phosphates: These form insoluble complexes with iron, reducing its absorption.
Enhancing Factors:
- Citrate and phosphorous: These can form soluble complexes with iron, enhancing its absorption.
Cellular Mechanisms involved in Fe absorption
Cellular Mechanisms
Low pH Environment: The acidic environment near the gastroduodenal junction facilitates the dissolution of iron, making it more available for absorption.
Ferric Reductase: This enzyme, located at the brush border of the epithelial cells, converts ferric iron (Fe³⁺) to the absorbable ferrous form (Fe²⁺).
Divalent Metal Transporter 1 (DMT1): This transporter protein moves iron from the apical surface of the intestinal epithelial cell into the cell.
Intracellular Storage and Transport:
Ferritin: Inside the cell, iron can be stored as ferritin.
Haphaestin: At the basal border of enterocytes, this enzyme converts iron back into the ferric form as it is transported into the plasma.
Haphaestin: At the basal border of enterocytes, this enzyme converts iron back into the ferric form as it is transported into the plasma.
What’s transferin & Total Iron-Binding Capacity (TIBC):?
Transferrin:
A glycoprotein produced in the liver that binds and transports iron in the plasma.
Each transferrin molecule can carry two atoms of iron.
Total Iron-Binding Capacity (TIBC):
Refers to the total capacity of transferrin to bind iron.
Typically, about 30% of transferrin’s iron-binding sites are occupied by iron at any given time.
Explain the Process of Iron Transport
Binding and Transport:
- After absorption, iron is bound by transferrin in the plasma.
- Transferrin-bound iron (Fe³⁺) is transported to various tissues, primarily to the bone marrow for erythropoiesis (production of red blood cells).
Delivery to Erythroblasts:
- In the bone marrow, transferrin delivers iron to erythroblasts (immature red blood cells).
- Transferrin binds to transferrin receptors on the surface of erythroblasts.
Endocytosis and Iron Release:
- The transferrin-receptor complex is internalized by endocytosis, forming an endosome.
- A proton pump in the endosome membrane increases the acidity inside the endosome (lowers the pH).
- The acidic environment causes iron to be released from transferrin into the cytoplasm of the erythroblast.
Recycling of Transferrin and Receptors:
- The transferrin molecule, now devoid of iron (called apotransferrin), and the transferrin receptor are recycled back to the cell surface.
- Apotransferrin is released into the plasma to bind more iron and continue the cycle.
Explain the Incorporation of Iron in Erythroid Precursors
Which enzymes catalyzes this?
When it’s inside what happens next?
In a healthy individual, about ____% of the nucleated cells in the bone marrow are sideroblasts.
Iron and Protoporphyrin to Form Haem
Inside the Cytoplasm: Once inside the cytoplasm of the erythroblast, iron is utilized for haem synthesis.
Formation of Haem: Iron is incorporated into protoporphyrin IX to form haem, a crucial component of hemoglobin.
Location of Reaction: This reaction takes place inside the mitochondria of the erythroblast cells.
Enzyme Involved: The enzyme ferrochelatase mediates the incorporation of iron into protoporphyrin IX to form haem.
Ferritin Storage
Iron Storage: In erythroblasts, iron that is not immediately used for haem synthesis is stored as ferritin.
Function of Ferritin: Ferritin acts as an intracellular iron storage protein, helping to maintain a balance of iron within the cells and protect them from iron-induced oxidative damage.
Sideroblasts
Definition: Sideroblasts are erythroblasts that contain aggregates of ferritin.
Bone Marrow Composition: In a healthy individual, about 25-30% of the nucleated cells in the bone marrow are sideroblasts.
Significance: The presence of sideroblasts indicates the availability of stored iron within the erythroblasts, ready for hae
&
Ferritin
Structure: Ferritin consists of a protein shell and an iron core.
Protein Shell: The protein shell is known as apoferritin and is spherical in shape.
Iron Core: The central core is composed of ferric oxyhydroxide molecules.
Solubility: Ferritin is water-soluble.
Mobilization: Iron stored in ferritin is readily mobilized for the synthesis of haemoglobin.
Relationship with Iron Stores: There is a linear relationship between the amount of circulating ferritin and body iron stores, meaning higher ferritin levels indicate higher iron stores.
Storage: Ferritin forms the majority of the body’s storage iron.
