IDA

Question 1

What’s the Total Body Iron in both male & female

Answer 1

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).

Question 2

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.

Question 3

Stored Fe is stored in what form?

Answer 3

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.

Question 4

These storage forms of Fe are primarily located in:

Answer 4

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.

Question 5

List the Proteins important in iron metabolism

Answer 5

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.

Question 6

• 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

Question 7

• 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

Question 8

What’s sideroblast

Answer 8

Erythroblasts containing ferritin aggregates are called sideroblasts.

Question 9

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.

Question 10

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.

Answer 10

ferritin & hemosiderin

Question 11

Iron Loss

Iron is lost from the body through the desquamation (shedding) of intestinal cells.

Question 12

What are the various Fe requirements in

adult male
Adolescent
Female of child bearing age
Pregnancy
Infant 5-12M
Infant 1-4M

Answer 12

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.

Question 13

What are the Factors Favoring Iron Absorption?

Answer 13

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.

Question 14

What are the Factors decreasing Iron Absorption?

Answer 14

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.

Question 15

What’s the Location of Fe Absorption in the git

Answer 15

Duodenum and Upper Jejunum: These are the primary sites for iron absorption due to their optimal environment and specialized cells

Question 16

What are the Forms of Iron Absorption

Answer 16

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.

Question 17

What are the retarding and enhancing chm/substance that affects Fe absorption

Answer 17

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.

Question 18

Cellular Mechanisms involved in Fe absorption

Answer 18

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.

Question 19

Haphaestin: At the basal border of enterocytes, this enzyme converts iron back into the ferric form as it is transported into the plasma.

Question 20

What’s transferin & Total Iron-Binding Capacity (TIBC):?

Answer 20

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.

Question 21

Explain the Process of Iron Transport

Answer 21

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.

Question 22

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.

Answer 22

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

Question 23

&

Question 24

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.

Question 25

Haemosiderin

Solubility: Haemosiderin is water-insoluble.

Formation: It is formed by ____

Visibility: Haemosiderin can be seen under light microscopy when stained using the Prussian blue reaction.

Haemosiderin is mainly found in?

Answer 25

Formation: It is formed by the lysosomal digestion of ferritin aggregates

Location: It is mainly found in macrophages, especially in the liver, spleen, and bone marrow.

Question 26

Between ferritin & haemosiderin which has a higher iron/protein content

Answer 26

Haemosiderin has a higher iron/protein content than ferritin

Question 27

The causes of Fe deficiency is classified into?
With possible causes

Answer 27

Inadequate intake

Defective Absorption:

• Subtotal Gastrectomy: Surgical removal of part of the stomach can impair iron absorption due to a reduction in the gastric acid necessary for converting ferric iron to the more absorbable ferrous form.
• Celiac Disease: An autoimmune disorder where the ingestion of gluten leads to damage in the small intestine, thereby reducing the surface area for absorption and leading to iron deficiency.

Excessive Loss of Iron:

• Gastrointestinal (GI) Bleeding: Conditions like oesophageal varices, hiatus hernia, peptic ulcers, and gastritis can cause significant blood loss.
• Hookworm Infestation: Hookworms attach to the intestinal wall and consume blood, leading to iron loss.
• Uterine Bleeding: Heavy menstrual bleeding (menorrhagia) or other forms of uterine bleeding can cause iron deficiency.
• Urinary Tract Bleeding: Blood loss through the urinary tract, although less common, can also contribute.
• Respiratory Tract Bleeding: Rare, but possible in conditions where there is significant bleeding in the respiratory tract.
• Bleeding Disorders: Conditions that impair blood clotting, leading to excessive bleeding, can result in iron deficiency.

Increased Requirement of Iron:

• Pregnancy: The growing fetus and placenta, along with increased blood volume, require additional iron.
• Infancy: Rapid growth during infancy increases the need for iron.
• Adolescence: During adolescence, the body undergoes rapid growth and development, increasing the iron requirement.

Question 28

What are the Features Specifically Related to Iron Deficiency

Answer 28

Features Specifically Related to Iron Deficiency

Pica: An abnormal and strong craving to eat non-nutritive substances such as clay, paint, cardboard, or coal. This behavior is often a sign of iron deficiency.

Koilonychia: Also known as “spoon nails,” this condition is characterized by thin, concave nails that may become brittle.

Angular Stomatitis: Inflammation and cracking at the corners of the mouth.

Atrophic Glossitis: A smooth, glossy tongue due to the loss of papillae, often accompanied by a burning sensation.

Plummer-Vinson Syndrome: This syndrome is a triad of iron deficiency anemia, dysphagia (difficulty swallowing), and glossitis. It is associated with an increased risk of esophageal cancer.

Question 29

What are the Clinical Features Related to the Cause of Iron Deficiency Anemia (IDA)

Answer 29

Haematemesis: Vomiting blood, which may indicate gastrointestinal bleeding.

Menorrhagia: Heavy menstrual bleeding, a common cause of iron loss in women of childbearing age.

Alteration in Bowel Habits: Changes in bowel habits, which may suggest colon cancer (colorectal carcinoma).

Signs of Malnutrition in Children: Poor growth, developmental delays, and other signs indicative of inadequate nutrition.

Question 30

What are the Laboratory Features of Iron Deficiency Anemia (IDA) in the 3 stages anemia goes through.

Answer 30

Depletion of Iron Stores

• Serum Ferritin: This is the most sensitive indicator of iron stores. In this stage, serum ferritin levels are low, reflecting depleted iron reserves. Since ferritin is an acute-phase reactant, it may be falsely elevated in inflammatory conditions, masking the depletion.
• Bone Marrow Iron Stain: A direct assessment, revealing absent or decreased iron stores in macrophages.

2. Iron-Deficient Erythropoiesis

• Serum Iron: Low levels of iron in the blood as iron stores are depleted.
• Total Iron-Binding Capacity (TIBC): Elevated, as the body attempts to capture more iron by increasing the production of transferrin, the protein that transports iron.
• Transferrin Saturation: Decreased, as there is less iron available to bind to transferrin. This is calculated as the ratio of serum iron to TIBC.
• Erythrocyte Protoporphyrin: Increased, as iron-deficient erythropoiesis leads to the accumulation of iron-free protoporphyrin in red blood cells.
• Serum Ferritin: Continues to decrease, confirming depleted iron stores.

3. Iron Deficiency Anemia

• Hemoglobin (Hb): Reduced levels, indicating anemia.
• Hematocrit (Hct): Decreased, reflecting the lower volume of red blood cells.
• Mean Corpuscular Volume (MCV): Low, indicating microcytic (small-sized) red blood cells.
• Mean Corpuscular Hemoglobin (MCH): Low, indicating hypochromic (pale) red blood cells.
• Red Blood Cell Distribution Width (RDW): Increased, showing greater variation in red blood cell size.
• Peripheral Blood Smear: Reveals microcytic, hypochromic red blood cells, often with anisocytosis (variation in size) and poikilocytosis (variation in shape).

Question 31

What are the results of Complete Blood Count (CBC) in IDA

Answer 31

Anemia: This refers to a reduction in the number of red blood cells (RBCs) or the amount of hemoglobin in the blood. In IDA, this is typically characterized by:

Low Hemoglobin and Hematocrit: Indicating fewer RBCs or reduced hemoglobin in the blood.

Decreased Red Cell Indices:

Mean Corpuscular Volume (MCV): Low MCV indicates microcytic (smaller than normal) red blood cells.

Mean Corpuscular Hemoglobin (MCH): Low MCH indicates hypochromic (paler than normal) red blood cells.

Thrombocytosis: An increase in the number of platelets. This can be a reactive process due to the body’s response to anemia.

Question 32

What are the usual findings in Peripheral Blood Film of IDA

Answer 32

Anisopoikilocytosis: Variation in the size (anisocytosis) and shape (poikilocytosis) of red blood cells. This is often seen in IDA due to the production of abnormal RBCs.

Microcytic Hypochromic Cells: Red blood cells that are smaller than normal (microcytic) and have less hemoglobin, making them paler (hypochromic).

Pencil Cells: Elliptocyte or pencil-shaped red blood cells, which are indicative of iron deficiency.

White Blood Cells (WBCs): These may be normal or slightly increased in number.

Platelets: Often increased in number on the blood film.

Question 33

What are the findings in Bone Marrow Aspiration of IDA

Answer 33

Bone Marrow Aspiration

Micronormoblastic Erythropoiesis:

• Smaller Erythroblasts: Erythroblasts (immature red blood cells in the bone marrow) are smaller than normal.
• Reduced Cytoplasm: The cytoplasm of these erythroblasts is reduced and may appear vacuolated (containing small cavities) with ragged borders.

Myelopoiesis: The production of myeloid cells (precursors of white blood cells) is normal.

Megakaryopoiesis: The production of megakaryocytes (precursors of platelets) is normal or increased.

Iron Stain:

• Perls’ Prussian Blue Reaction: This is a staining method used to detect iron in tissues.
• Absence of Stainable Iron: In IDA, there is a lack of stainable iron in the bone marrow, indicating depleted iron stores.

Question 34

What’s the function
Normal range, values and interpretation in IDA
& drawback of using Serum Ferritin

Answer 34

Function: Reflects the amount of storage iron in the body.

Normal Range: 15-300 µg/L.

Interpretation:

Below 12 µg/L strongly suggests depleted iron stores.

Higher levels indicate greater storage iron.

• Drawbacks:

Non-specific: Levels can increase due to acute phase reactions (inflammation, infection).

Question 35

What are the normal range, function & interpretation of
Serum Iron
Total Iron Binding Capacity (TIBC)

Answer 35

Serum Iron

Normal Range: 50-150 µg/dL.

Interpretation:

Low levels seen in iron deficiency anemia (IDA), chronic inflammation, and malignancy.

Provides direct measurement of iron in the blood plasma.

Total Iron Binding Capacity (TIBC)

Normal Range: 300-400 µg/dL.

Function: Reflects the capacity of transferrin to bind iron.

Interpretation:

Increased in IDA: Indicates increased binding capacity of transferrin due to low serum iron levels.

Decreased in iron overload conditions.

Question 36

What are the normal range, function & interpretation of
Transferrin Saturation

Answer 36

Transferrin Saturation

Normal Range: Typically around 30%.

Function: Indicates the percentage of transferrin that is saturated with iron.

Interpretation:

Normal saturation: Around 30%.

<15% in IDA: Indicates low iron availability to bind to transferrin due to low serum iron or increased TIBC.

Question 37

Explain the function & interpretation of Serum Transferrin Receptor Assay & Free Erythrocyte Protoporphyrin (FEP)

Answer 37

Serum Transferrin Receptor Assay

Function: Measures the amount of transferrin receptors in the blood.

Interpretation:

Increased in iron deficiency anemia (IDA) due to an upregulation of transferrin receptors on erythroid precursors.

More reliable than serum ferritin as it is not affected by acute phase reactions.

Free Erythrocyte Protoporphyrin (FEP)

Function: Assesses the level of protoporphyrin in erythrocytes, which combines with iron to form heme in the mitochondria of erythroid precursors.

Interpretation:

Increased in IDA because the lack of iron prevents the formation of heme, leading to an accumulation of protoporphyrin.

Also elevated in anemia of chronic disease (ACD) and lead poisoning.

Normal levels in thalassemia, as the primary defect lies in globin synthesis rather than heme synthesis.

Question 38

What are the Differential Diagnosis & why do you think so? /i.e characteristics

Answer 38

Thalassemia Minor

Characterized by microcytic, hypochromic anemia.

Normal or increased serum ferritin and iron.

Normal or decreased TIBC.

Normal or decreased transferrin saturation.

Anemia of Chronic Disease (ACD)

Usually normocytic or microcytic anemia.

Low serum iron, but normal or increased serum ferritin (due to increased iron storage in response to inflammation).

Decreased TIBC.

Low transferrin saturation.

Sideroblastic Anemia

Characterized by the presence of ringed sideroblasts in the bone marrow.

Increased serum iron and ferritin.

Normal or decreased TIBC.

High transferrin saturation.

Question 39

What is the Treatment of Iron Deficiency Anemia (IDA)
Side effects & considerations

Answer 39

Oral Iron Therapy

Common Preparations: Ferrous sulfate 200 mg (contains 60 mg elemental iron).

Response to Therapy:

Reticulocytosis: Develops within one week and peaks between 8-10 days.

Hemoglobin Rise: Gradual increase of 1 g/dL in 4 weeks.

Duration: 6-8 weeks needed for hemoglobin restoration, with therapy continuing for a total of 6 months to replenish body iron stores.

Side Effects:

Gastrointestinal symptoms such as vomiting, constipation, diarrhea, and gastritis.

Parenteral Iron Therapy

Indications:

Intolerance to oral iron.

Advanced stage of pregnancy with moderate to severe anemia.

Malabsorption conditions.

Question 40

• CROSS CHECK IMAGE (A MUST)