Anemia of Disordered Iron Metabolism and Heme Synthesis

Most common amenia worldwide

Iron Deficiency Anemia

A cause of IDA is decreased intake of iron ie

Inadequate iron intake (vegetarian)

A cause of IDA is an increased need for iron ie

pregnant/lactating women or growing children

A cause of IDA is an increased loss of iron ie

Menstruation, chronic GI bleed, intravascular hemolysis

Pathogenesis

Development of the disease

IDA has 3 stages of iron depletion. Which department depletes first?

Storage Iron

What is the second stage of iron depletion in IDA?

Transport Iron

What is the 3rd and last stage of iron depletion in IDA?

Functional Iron

What stage of IDA has Normal HGB, Normal Serum Iron, Normal TIBC, and decreased Ferritin?

Stage 1- Storage Iron depletion

What stage of IDA has Normal HGB, Decreased Serum Iron, Increased TIBC, and decreased Ferritin?

Stage 2- Transport Iron depletion

What stage of IDA has decreased HGB, decreased Serum Iron, Increased TIBC, and decreased ferritin?

Stage 3- Functional iron depletion

What stage of IDA will patient be in full-blown anemia and begin to develop generic anemia symptoms?

Stage 3

Why is TIBC of Transferrin increasing as Iron is depleting?

Think of it like a bus driver with a bus full of empty seats. This man needs the money, so he wants butts in seats. He has a large capacity to take more people than if he had a full bus. 

What is pica? And what anemia is it associated with?

Craving weird foods like dirt or chalk; IDA

The percent saturation of transferrin is … in IDA

decreased

Protoporphyrin complexed to zinc instead of Fe (ZPP) is … during IDA

Increased

A specialized test for IDA is bone marrow stain with Prussian blue to see hemosiderin. What is hemosiderin?

A storage form of iron

Where is hemosiderin and ferritin found?

Liver, BM, and spleen

Common way to treat IDA are…

iron supplements

What is the blood picture of IDA?

Hypochromic, microcytic anemia

In IDA there is an increased … indicating that there is greater variation in the size of RBCs

RDW (Red Cell Distribution Width)

Anemia of chronic disease (ACD) is also known as…

Chronic Inflammation

What anemia is common amongst hospital patients?

ACD

What is the paradox of ACD? Hint: it is what differentiates it from IDA

Iron is abundant in body stores. It is just not reaching the cells therefore slowing down production

Another word for iron deficiency is…

Sideropenia

What causes the sideropenia of ACD?

All the above

What is neutrophil lactoferrin?

Iron-binding protein found in the granules of neutrophils.

How does neutrophil lactoferrin cause sideropenia?

It scavenges available iron when stimulated by Hepcidin in order to restrict pathogen growth

Is Ferritin an acute phase reactant?

yes

How does increased ferritin cause sideropenia in ACD?

There is an increased storage of Iron, making it unavailable for HGB

Do cytokines contribute to sideropenia of ACD?

Yes, inhibits erythropoiesis by inhibit EPO

What does a blood picture look like for ACD?

Normochromic, normocytic anemia

What anemia is this?

Usually mild

• Increased to normal ferritin

• Decreased serum iron

• Decreased TIBC

• Decreased or normal %Sat

• Normal RDW

ACD

Treatment of ACD

Anything that diminishes the underlying inflammation, but usually anemia is mild enough to not need treatment

What type of synthesis is impaired in Sideroblastic Anemia?

Heme 

Etiology

Cause of disease

Etiologies of Sideroblastic Anemia are hereditary causes, drugs, and what type of metal poisoning?

Lead

Leading poisoning in children can lead to impaired … development

mental

Symptoms of Sideroblastic Anemia include all except

Pica

Blood Picture of Sideroblastic Anemia

• normochromic, normocytic anemia

• RDW normal 

• Basophilic stippling

• Pappenheimer bodies

• BM has Iron ring around the mitochondria of developing RBCs

Why is basophilic stippling characteristic of Sideroblastic anemia?

Lead slows the breakdown in RNA

Why are pappenheimer bodies characteristic of Sideroblastic anemia?

Because they are made of Iron deposits

Treatments of Sideroblastic Anemia include

Both

Hemochromatosis is a genetic abnormality and is most common in people of … descent

European

Hemochromatosis involves a deficiency of…

Hepcidin

What is hepcidin?

A hormone produced by the liver to regulate iron metabolism

What will Hepcidin deficiency lead to?

Increased Iron absorption and uncontrolled release of Iron from macrophages into plasma

Therapeutic phlebotomy and Iron chelation are treatments for…

Hemochromatosis

Porphyrias is an inherited disease that blocks … synthesis

Porphyrin

What is porphyrin again?

The ring of heme that chelates iron

What enzyme is deficient in Congenital Erythropoietic Porphyria (CEP)?

Uroporphyrinogen III synthase

what are clinical features of CEP?

severe photosensitivity, blistering, red urine, hemolytic anemia, and erythrodontia (red-brown teeth)

What enzyme is deficient in Erythropoietic Protoporphyria (EPP)?

Ferrochelatase

What distinguishes EPP and CEP clinically?

EPP causes more moderate photosensitivity without blistering while CEP has intense photosensitivity with blistering and scars

What is a hallmark laboratory finding in EPP?

elevated free protoporphyrin in RBCs, plasma, and feces

EPP accumulates protoporphyrin which is water … so its excreted in …

insoluble, feces

CEP accumulates uroporphyrin and coproporphyrin which are water … so its excreted in …

soluble, urine