Anemia of chronic disease (Year of the Zebra)

Summary

The video script discusses 'anemia of chronic disease,' a condition characterized by low red blood cell count associated with chronic illnesses like infections, cancer, and autoimmune disorders. It explains how chronic inflammation disrupts iron metabolism, hindering red blood cell production. The script details the role of iron in hemoglobin and its absorption process, and outlines the complex mechanisms behind the disease, including cytokines' impact on erythropoietin production and iron sequestration. Symptoms are typically mild, and treatment focuses on addressing the underlying cause, with potential use of intravenous iron or erythropoietin in severe cases.

Takeaways

• 🩸 'Foreign disease' or anemia of chronic disease is characterized by low red blood cell (RBC) count associated with chronic conditions like infections, malignancy, diabetes, or autoimmune disorders.
• 🔍 The term 'anemia of chronic inflammation' was previously used due to the continuous inflammation from chronic diseases impairing iron metabolism and RBC production.
• 🌟 RBCs, produced in the bone marrow in response to erythropoietin, are rich in hemoglobin, a protein that binds oxygen, making RBCs essential oxygen transporters.
• 🧬 Hemoglobin molecules consist of four heme groups, each containing iron, allowing them to bind up to four oxygen molecules.
• 🥗 Iron, crucial for RBC and hemoglobin production, is absorbed from the diet in the small intestine after being oxidized from Fe2+ to Fe3+ by the enzyme hephestin.
• 🔄 In chronic disease, the anemia mechanism involves decreased RBC lifespan due to cellular destruction and decreased RBC production due to dysregulation of iron homeostasis.
• 🧬 Cytokines like tumor necrosis factor alpha and interferon gamma inhibit erythropoietin production and promote RBC degradation, contributing to anemia.
• 🔗 IL-10 and IL-6 are involved in the sequestration of iron within macrophages and the inhibition of iron absorption from the intestine, respectively.
• 💉 Symptoms of anemia of chronic disease are typically mild, including fatigue, pallor, and shortness of breath, especially with physical exertion.
• 🩺 Diagnosis often involves a complete blood count and iron studies, revealing low serum iron, normal to low transferrin saturation, and elevated ferritin levels.
• 🛑 Treatment focuses on addressing the underlying chronic disease and may include intravenous iron therapy or erythropoietin injections in severe cases.

Q & A

What is the term used to describe a low red blood cell count associated with chronic diseases?

The term used is 'anemia of chronic disease', which is also referred to as 'disease anemia'.

What are the chronic diseases that can lead to anemia of chronic disease?

Chronic diseases such as infections, malignancy, diabetes, and autoimmune disorders can lead to anemia of chronic disease.

How does chronic inflammation contribute to the development of anemia of chronic disease?

Chronic inflammation impairs iron metabolism and RBC production, leading to the development of anemia of chronic disease.

What is the role of erythropoietin in RBC production?

Erythropoietin is a molecule secreted by the kidneys in response to low oxygen levels in the blood, which stimulates the production of RBCs in the bone marrow.

What is the function of hemoglobin in red blood cells?

Hemoglobin binds to oxygen, allowing red blood cells to transport oxygen to tissues throughout the body.

How is iron absorbed in the body, and where does it primarily take place?

Iron is absorbed in the small intestine, specifically the duodenum, where it is released as Fe2+ ions and then oxidized to Fe3+ ions for absorption.

What is the role of transferrin in iron transport within the body?

Transferrin is an iron transport protein that carries iron in the blood to various target tissues for use in processes like hemoglobin production.

What are the two main mechanisms that contribute to anemia of chronic disease?

The two main mechanisms are decreased RBC lifespan due to direct cellular destruction and decreased RBC production due to dysregulation of iron homeostasis and signals controlling RBC production.

Which cytokines are involved in the pathogenesis of anemia of chronic disease?

Cytokines such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10) play a role in the pathogenesis of anemia of chronic disease.

What are the typical symptoms of anemia of chronic disease?

Symptoms include fatigue, pallor, and shortness of breath, particularly during physical activity like walking up stairs.

How is anemia of chronic disease typically diagnosed, and what lab findings might be observed?

It is usually discovered incidentally during workup for a chronic disease. Lab findings may include low serum iron, normal to low serum iron binding capacity, low transferrin saturation, and normal or increased serum ferritin levels.

What are the treatment options for anemia of chronic disease?

Treatment involves correcting the underlying chronic disease process. In severe cases, intravenous iron therapy, RBC transfusions, or erythropoietin injections may be used to improve symptoms.

Outlines

00:00

🩸 Understanding Anemia of Chronic Disease

This paragraph delves into the concept of 'anemia of chronic disease,' a condition characterized by low red blood cell (RBC) count associated with chronic diseases like infections, cancer, diabetes, and autoimmune disorders. It was historically known as 'anemia of chronic inflammation,' highlighting the role of continuous inflammation from chronic diseases in impairing iron metabolism and RBC production. The anemia is typically mild and the second most common form of iron deficiency anemia. The paragraph explains the role of erythropoietin in RBC production in response to low blood oxygen levels and the structure and function of hemoglobin and myoglobin, which are crucial for oxygen transport and storage. It also details the process of iron absorption from the diet, its conversion to iron III by hephestin in the duodenum, and its storage and transport mechanisms. The paragraph further explores the complex mechanisms behind anemia of chronic disease, including decreased RBC lifespan due to cellular destruction and decreased RBC production due to dysregulation of iron homeostasis and erythropoiesis signals, influenced by cytokines like tumor necrosis factor alpha, interferon gamma, and IL-10. These cytokines inhibit erythropoietin production, promote RBC degradation, and sequester iron, leading to inadequate iron for hemoglobin production. Symptoms of the anemia are generally mild, including fatigue, pallor, and shortness of breath, especially with physical exertion. Diagnosis often involves a complete blood count and iron studies, revealing low serum iron, normal to low transferrin saturation, and elevated ferritin levels, with hepsidin levels being less commonly assessed.

05:01

💊 Treatment and Management of Anemia of Chronic Disease

The second paragraph focuses on the treatment and management of anemia of chronic disease. It emphasizes that addressing the underlying chronic condition is essential for treating the anemia. For instance, treating infections with antibiotics, removing tumors surgically, or improving blood glucose control in diabetes can resolve the anemia. In cases where hemoglobin levels fall significantly below 7 grams per deciliter, intravenous iron therapy, red blood cell transfusions, or erythropoiesis-stimulating agents (ESAs) like epoetin alpha or darbepoetin alpha may be administered to alleviate symptoms. The paragraph concludes with a recap, summarizing that anemia of chronic disease is a condition arising from chronic diseases and is mediated by inflammatory factors. Treatment strategies aim to correct the underlying condition, and in severe cases, may involve RBC transfusions or erythropoietin injections.

Keywords

💡Red Blood Cells (RBCs)

Red blood cells, or RBCs, are the most common type of blood cell and are responsible for transporting oxygen throughout the body. In the context of the video, RBCs are crucial for understanding anemia of chronic disease, as they may be low in number due to chronic conditions. The video explains that RBCs are produced in the bone marrow in response to erythropoietin, a hormone that signals the need for more oxygen transporters when oxygen levels are low.

💡Anemia

Anemia refers to a condition where there is a deficiency of red blood cells or hemoglobin in the blood, leading to decreased oxygen-carrying capacity. The video discusses anemia of chronic disease, a type of anemia associated with chronic conditions like infections, malignancy, diabetes, or autoimmune disorders. It is characterized by mild anemia due to the body's inflammatory response impairing RBC production.

💡Erythropoietin

Erythropoietin is a hormone produced by the kidneys that stimulates the production of red blood cells. The video explains that erythropoietin is secreted in response to low oxygen levels in the blood, prompting the bone marrow to produce more RBCs. In chronic disease, the production of erythropoietin can be inhibited, contributing to anemia.

💡Hemoglobin

Hemoglobin is an iron-containing protein in red blood cells that binds to oxygen, allowing RBCs to transport oxygen to tissues. The video describes how each hemoglobin molecule can bind up to four molecules of oxygen, highlighting its importance in oxygen transport. Hemoglobin's function is compromised in anemia of chronic disease due to inadequate iron for its production.

💡Iron Metabolism

Iron metabolism refers to the process by which the body absorbs, transports, stores, and utilizes iron, which is essential for the production of hemoglobin. The video explains that in chronic disease, this process is impaired, leading to a decrease in available iron for RBC production and contributing to anemia.

💡Cytokines

Cytokines are signaling molecules that mediate and regulate immunity and inflammation. The video discusses how certain cytokines, such as tumor necrosis factor alpha and interferon gamma, play a role in the pathogenesis of anemia of chronic disease by inhibiting erythropoietin production and promoting RBC destruction.

💡Inflammation

Inflammation is part of the body's immune response to harmful stimuli, such as pathogens or damaged cells. The video describes how chronic inflammation, a hallmark of many chronic diseases, can lead to anemia by impairing iron metabolism and RBC production.

💡Transferrin

Transferrin is an iron-binding protein that transports iron in the blood. The video explains that iron is carried by transferrin to various target tissues, including those involved in RBC production. In anemia of chronic disease, the availability of iron bound to transferrin can be reduced, impacting hemoglobin synthesis.

💡Ferritin

Ferritin is an iron storage protein found in cells. The video describes how iron is temporarily stored as ferritin within cells and is released when needed for processes like hemoglobin production. In chronic disease, ferritin can sequester more iron, making it less available for RBC production.

💡Hepcidin

Hepcidin is a peptide hormone that regulates iron absorption and distribution. The video mentions that in chronic disease, IL-6 can increase the production of hepcidin, which in turn blocks the uptake of iron from the small intestine, contributing to the development of anemia.

💡Treatment of Anemia

The treatment of anemia, as discussed in the video, involves addressing the underlying chronic disease. This can include treatments like antibiotics for infections, surgery for tumors, or improved blood glucose control for diabetes. In cases of severe anemia, intravenous iron therapy or erythropoietin injections may be used to improve symptoms.

Highlights

Foreign disease, or anemia of chronic disease, is characterized by low red blood cell (RBC) count associated with chronic conditions like infections, malignancy, diabetes, or autoimmune disorders.

The disease was previously called anemia of chronic inflammation due to the continuous inflammation caused by chronic diseases.

Anemia of chronic disease impairs iron metabolism and RBC production, typically presenting as mild anemia.

RBCs are produced in the bone marrow in response to erythropoietin, a molecule secreted by the kidneys in response to low oxygen levels.

Hemoglobin, a protein in RBCs, binds to oxygen, making RBCs effective oxygen transporters.

Each hemoglobin molecule can bind up to four molecules of oxygen, facilitated by iron in its heme structures.

Iron is also crucial for proteins like myoglobin and cytochrome oxidase, which are involved in oxygen delivery and ATP generation.

Iron required for RBC production comes from dietary sources and is absorbed in the small intestine, particularly the duodenum.

Hephaestin, an enzyme in the duodenal cells, oxidizes iron from Fe2+ to Fe3+, which then binds to ferritin for storage.

When needed, iron is released from ferritin, binds to transferrin, and is transported to target tissues for utilization.

Anemia of chronic disease involves a two-fold mechanism: decreased RBC lifespan and decreased RBC production.

Shortened RBC lifespan can be due to direct cellular destruction by toxins from cancer cells, viruses, or bacterial infections.

Decreased RBC production is complex and involves dysregulation of iron homeostasis and RBC production signals.

Cytokines, such as tumor necrosis factor alpha and interferon gamma, inhibit erythropoietin production and promote RBC degradation.

Interferon gamma increases the expression of divalent metal transporter one, enhancing iron uptake by macrophages and reducing iron availability for hemoglobin production.

IL-10 mediates increased expression of ferritin receptors on macrophages, sequestering more iron.

IL-6 increases hepcidin production in the liver, blocking further iron uptake from the small intestine.

Symptoms of anemia of chronic disease are mild, including fatigue, pallor, and shortness of breath, especially with physical activity.

Anemia of chronic disease is usually discovered incidentally during workup for a chronic disease, with complete blood count showing mildly decreased hemoglobin.

Iron studies typically show low serum iron levels, normal to low serum iron transferrin, low transferrin saturation, and normal or increased serum ferritin levels.

Treatment of anemia of chronic disease involves correcting the underlying condition and may include intravenous iron therapy or erythropoietin injections in severe cases.

Transcripts

foreign

disease refers to a low red blood cell

or RBC that may be associated with many

chronic disease States like infections

malignancy diabetes or autoimmune

disorders

the disease used to be called anemia of

chronic inflammation because the

underlying cause of anemia is the

continuous inflammation generated by

chronic disease which impairs iron

metabolism and in turn RBC production

the anemia itself is usually mild and

it's the second most common type of iron

deficiency anemia

rbcs are produced in the bone marrow in

response to erythropoietin which is a

molecule secreted by the kidneys in

response to low levels of oxygen in the

blood

taking a closer look at our rbcs we can

see they're loaded with millions of

copies of the same exact protein called

hemoglobin which binds to oxygen and

turns our rbcs into little oxygen

Transporters that move oxygen to all the

tissues in our body zooming in even

closer each hemoglobin molecule is made

up of four smaller heme molecules which

have iron right in the middle oxygen

binds to the iron so each hemoglobin

molecule can bind four molecules of

oxygen

in addition iron is also an important

part of proteins like myoglobin which

delivers and stores oxygen in muscles

and mitochondrial enzymes like

cytochrome oxidase which help generate

ATP

now we get the iron required for RBC

production from our diet following

breakdown of food in the stomach iron is

released as fe2 plus ions and then it's

absorbed in the small intestine

specifically the duodenum

inside the duodenal cells an enzyme

called hephestin oxidizes Iron II plus

to iron three plus ions this form of

iron binds to a protein called ferritin

which temporarily stores the iron

when iron is needed in the body some

iron molecules are released from

ferritin and transported into the blood

where they bind to an iron transport

protein called transferrin that carries

iron to various Target tissues and

releases them there

now the mechanisms that underlie anemia

of chronic disease are complex and still

under investigation in general the

disease mechanism is a two-fold process

decreased RBC lifespan and decreased RBC

production

shortened RBC lifespan is a result of

direct cellular destruction via toxins

from cancer cells viruses or bacterial

infections decreased RBC production is a

bit more complex and involves several

mechanisms

the most important one and the one that

most researchers agree upon involves

dysregulation of iron homeostasis and

the signals that control RBC production

in chronic disease States chemical

Messengers called cytokines mediate this

pathologic process in the kidney immune

system and the GI tract

two cytokines called tumor necrosis

Factor Alpha and interferon gamma

inhibit the production of erythropoietin

in the kidney which subsequently

prevents RBC production in the bone

marrow additionally tumor necrosis

Factor Alpha promotes RBC degradation in

macrophages via phagocytosis an

interferon gamma increases the

expression of a protein Channel called

divalent metal transporter one on the

surface of macrophages

this channel serves as a pathway for

iron to enter the macrophage at

increased rates so less iron is

available for the production of

hemoglobin another cytokine called il-10

mediates the expression of increased

ferritin receptors on the surface of

macrophages which then sequesters even

more iron

finally il-6 also works in the liver by

increasing production of a molecule

called hepsidin which blocks further

uptake of iron from the small intestine

the culmination of all these processes

results in inadequate iron available for

the production of hemoglobin so with

either being locked up in macrophages or

unable to be absorbed fully productive

hemoglobin-laden rbcs cannot be produced

symptoms of anemia of chronic disease

are usually mild including fatigue

pallor and shortness of breath and the

latter is usually associated with

physical activity like walking up three

flights of stairs

anemia of chronic disease is usually

discovered incidentally during the

workup for a chronic disease process a

complete blood count usually shows

mildly decreased hemoglobin usually

between 10 and 12 grams per deciliter

initially the anemia is normocytic which

means that rbcs have a normal size but

eventually it can become microcytic

meaning rbcs get smaller iron studies

Show Low serum iron levels normal to low

serum iron transfer in or total iron

binding capacity low transferring

saturation and normal or increased serum

ferritin levels

pepcidin levels are also usually

elevated although assays to detect

hepsidin levels are not widely available

bone marrow examination while not

routinely performed in the assessment of

anemia of chronic disease can

demonstrate macrophages with increased

iron stores and erythroid precursor

cells

treatment of anemia of chronic disease

requires correcting the underlying

problem or disease process for example

if the anemia is due to an infection

appropriate treatment with antibiotics

may be necessary if a person has a tumor

surgical removal of the tumor may lead

to resolution of the anemia similarly if

the anemia is due to diabetes improved

blood glucose control may result in an

improvement in the anemia

intravenous iron therapy can sometimes

be useful and when hemoglobin levels

fall below 7 grams per deciliter

transfusions with packed rbcs or

erythropoietic agents like a poetin

alpha or Darby poetin Alpha may be given

to improve symptoms

all right as a quick recap anemia of

chronic disease occurs in the context of

chronic disease States like infections

malignancy diabetes and autoimmune

conditions the mechanism of disease is

largely mediated by inflammatory factors

including hepsidin treatment involves

correcting the underlying condition or

in severe cases RBC transfusions or

erythropoietin injections

helping current and future clinicians

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