Anemia 1. Definition 2. Symptoms

1. Decrease in the number of RBCs in the blood, resulting in reduced oxygen-carrying capacity 2. Symptoms: fatigue, dyspnea (on exertion), weakness \ \ \ With more severe anemia, may see confusion, tachycardia, hypotension, syncope, and death

Iron 1. Absorption - Where is it absorbed? - Forms?

First and second portions of the duodenum Forms: - Reduced +2 (Ferrous) or +3 (Ferric) state (Ferric is useless to us) - Heme Iron - Gluconate, sulfate - Role of pH, food (absorbed better in low pH/acidic)

Iron 1. Dietary Sources - Most easily absorbed? - Plants/Vegetarians? - Geritol?

- Heme iron is most easily absorbed - Plants are a poor source (have Fe 3+ if they do) - Vegetarians at risk for deficiency Supplement with Geritol

Iron Absorption at the Enterocyte 1. Describe the Process

\ \ \ _Heme_ Iron is absorbed by heme transporter then bound to Mucosal Ferritin (protects from redox reactions) - Fe 2+ leaves the enterocyte into the extracellular space via Ferroportin 1 (_inhibited_ by Hepcidin), is oxidized by Hephaestin (copper containing molecule) to Fe 3+ (Ferric form) - Binds Plasma Transferrin in the blood \ \ \ _Nonheme_ iron does the same, except is converted to Fe 2+ by Duodenal Cytochrome B first and then taken up by DMT 1

Iron Loss 1. Insensible loss 2. Vascular loss

Insensible: sweat and endothelial sloughing Vascular: - External loss (traumatic) - Sequestration (hematoma) - Menstrual - Internal loss (GI) --\> Gastroduodenal (ulcer, espophageal varices), Colonic (tumors, diverticulitis)

Iron Deficiency Anemia 1. Lab Values - Hgb/Hct - MCV - Ferritin - Transferrin Saturation - TIBC - Reticulocytosis

Hgb/Hct low MCV low Ferritin low (both intracellular (can't be measured) and vascular) - Very accurate indirect measurement of total iron body stores - Ferritin of 10 or less is 99% sensitive/specific for \ \ \ Iron deficiency anemia\ \ \ Transferrin Saturation low (Transferrin itself will be high) TIBC high (measures transferrin ^^^) Reticulocytosis

Microcytic Anemia Flashcards by Christopher Hauglid

Anemia

Definition
Symptoms

Decrease in the number of RBCs in the blood, resulting in reduced oxygen-carrying capacity
Symptoms: fatigue, dyspnea (on exertion), weakness

***With more severe anemia, may see confusion, tachycardia, hypotension, syncope, and death

How well did you know this?

Not at all

Perfectly

Anemia

How to categorize? (4)

Size, Color, Chronicity, Etiology

How well did you know this?

Not at all

Perfectly

Hypochromic Microcytosis

How well did you know this?

Not at all

Perfectly

What is a normal Hb in Males? Females?

Males = 14 to 17.5 g/dL

Females = 12 to 15 g/dL

How well did you know this?

Not at all

Perfectly

What is a normal Hct in Males? Females?

Males = 42-50%

Females = 36-44%

How well did you know this?

Not at all

Perfectly

What is a normal RBC count in Males? Females?

Males = 4.5 - 6.0 Million

Females = 4.0 to 5.0 Million

How well did you know this?

Not at all

Perfectly

What is a normal MCV?

80-100 fL

How well did you know this?

Not at all

Perfectly

What is a normal MCH?

30-34 pg

How well did you know this?

Not at all

Perfectly

What is a normal MCHC? (i.e. Hgb/Hct x 100)

30-36%

How well did you know this?

Not at all

Perfectly

What is a normal RDW? (Red Cell Distribution Width)

13-15%

How well did you know this?

Not at all

Perfectly

What does a large RDW mean? small?

Large = Size is all over the map

Small = Uniform in size

How well did you know this?

Not at all

Perfectly

Iron

Absorption
- Where is it absorbed?
- Forms?

First and second portions of the duodenum

Forms:

Reduced +2 (Ferrous) or +3 (Ferric) state (Ferric is useless to us)
Heme Iron
Gluconate, sulfate
Role of pH, food (absorbed better in low pH/acidic)

How well did you know this?

Not at all

Perfectly

Iron

Dietary Sources
- Most easily absorbed?
- Plants/Vegetarians?
- Geritol?

Heme iron is most easily absorbed
Plants are a poor source (have Fe 3+ if they do)
Vegetarians at risk for deficiency

Supplement with Geritol

How well did you know this?

Not at all

Perfectly

Iron Absorption at the Enterocyte

Describe the Process

***Heme Iron is absorbed by heme transporter then bound to Mucosal Ferritin (protects from redox reactions)

Fe 2+ leaves the enterocyte into the extracellular space via Ferroportin 1 (inhibited by Hepcidin), is oxidized by Hephaestin (copper containing molecule) to Fe 3+ (Ferric form)
Binds Plasma Transferrin in the blood

***Nonheme iron does the same, except is converted to Fe 2+ by Duodenal Cytochrome B first and then taken up by DMT 1

How well did you know this?

Not at all

Perfectly

Hepcidin

Role
Upregulation
Downregulation

Role: Reduces iron absorption by blocking ferroportin

Upregulated: by IL-6, high circulating ferritin

Downregulated: by low ferritin, hypoxia

How well did you know this?

Not at all

Perfectly

Erythropoietin

Produced where?
Use in Anemias?
Therapeutic Use

Produced by renal fibroblasts in response to hypoxia

Not useful in anemias that are already EPO-abundant (e.g. iron deficiency)

Should be co-administered with parenteral iron

How well did you know this?

Not at all

Perfectly

Iron Distribution in the Body

4 parts

Circulating RBCs 2500 mg

Fe-containnig Proteins (e.g. Ferritin) 400 mg

Transferrin-bound 3-7 mg

Storage (marrow, RES) 1000 mg

How well did you know this?

Not at all

Perfectly

Iron Loss

Insensible loss
Vascular loss

Insensible: sweat and endothelial sloughing

Vascular:

External loss (traumatic)
Sequestration (hematoma)
Menstrual
Internal loss (GI) –> Gastroduodenal (ulcer, espophageal varices), Colonic (tumors, diverticulitis)

How well did you know this?

Not at all

Perfectly

Iron Deficiency Anemia

Lab Values
- Hgb/Hct
- MCV
- Ferritin
- Transferrin Saturation
- TIBC
- Reticulocytosis

Hgb/Hct low

MCV low

Ferritin low (both intracellular (can’t be measured) and vascular)

Very accurate indirect measurement of total iron body stores
Ferritin of 10 or less is 99% sensitive/specific for ***Iron deficiency anemia***

Transferrin Saturation low (Transferrin itself will be high)

TIBC high (measures transferrin ^^^)

Reticulocytosis

Reticulocytosis

Normal Lab Values

Serum Fe
TIBC
Saturation
Ferritin

Serum Fe 60-150 mcg/dL

TIBC 300-360 mcg/dL

Saturation 20-50%

Ferritin 40-200 mcg/L ***Excellent indicator of total body iron***

Iron Deficiency Anemia

Common Causes

Detailed history is essential
> 50 y.o. GI malignancy until proven otherwise
IBD
Ulcer/esophagitis
Vascular malformations
Hematoma, sequestration (rare)
Gynecologic loss

Iron Deficiency

Signs and Symptoms (5)

Pica (chewing ice)/Pagophagia (chewing on/eating clay)

Restless Legs Syndrome

Pallor/Pale palmar creases/Pale Conjunctiva

Glossitis

Nail Changes

How much iron can be absorbed per day if given orally?

How much can be given IV?

Absorbed Orally: 25 mg

IV: 500 mg

**Anemic of Chronic Disease** 1. Hepcidin - What is it? - Effects? - Induced/Stimulated by?

Hepcidin - An **acute phase reactant** - Has an **antibacterial effect** (presumably by limiting Fe-dependent electron transport) - **IL-6** is a potent stimulator of hepcidin production - **TNF, IFa, IFy** also induce hepcidin (elevated in **anemias of autoinflammation, cancer**)

What is this and what disease does this patient have?

Microcytic Hypochormic Anemia (with **Rouleaux formation** (i.e. clumping of cells)) Seen in **Rheumatoid Arthritis** (i.e. **Anemia of Chronic Disease**)

**Anemia of Renal Disease** 1. Type of Anemia 2. Mechanism

Usually a **normochromic anemia** Increased **RBC destruction** (lysis with azotemia (minor contribution)) Anemia unrecognized by diseased renal fibroblasts **NO** erythropoietin surge **NO** marrow stimulation

**Thalassemia** 1. Alpha-like globins (1 major) 2. Beta-like globins (4 major)

Alpha-like: **alpha**, zeta, and xi Beta-like: **beta, gamma, delta, epsilon**

\*\*\*Important\*\*\* How many alpha alleles do we have and on which chromosome?

**Two alpha alleles** per chromosome (**4 total**) Chromosome **16** \*\*\*only one copy of all Betas on chromosome **11**\*\*\*

How are Thalassemias named?

For the **gene that is deficient**

**a⁺-thalassemia** 1. Missing **one** allele 2. Missing **two** alleles 3. Missing **three** alleles

Missing... **One:** a₂B₂ --\> **Silent** carrier ---\> asymptomatic **Two:** 85-95% a₂B₂ --\> a⁺-thal **trait** --\> **mild anemia** (no tx. required) **Three:** 5-30% Hgb H (B₄) "**Hgb H disease**"

**a⁰-thalassemia**

(no alpha chains) B₄, Y₄ --\> a⁰-thal --\> **Fetal Hydrops** (Lethal)

What is a hallmark for **Thalassemias** on PBS?

**Target Cells**

alpha-thalassemia **trait**

Hemoglobin H Disease ( --/-a, B₄)

Hemoglobin **Bart's** **Fetal Hydrops** (NO functional hemoglobin)

**B-Thalassemia** 1. B⁺-Thalassemia 2. B⁰-Thalassemia

B⁺-Thalassemia: B-thal **trait** or B-thalassemia **minor** B⁰-Thlassemia: B-thalassemia **major** - **No** Hb A, **Mostly** Hb **F** and some Hb A₂ - **_Severe, transfusion-dependent_** \*\*\***B-Thalassemia** tends to be **_more severe_**, as there are only 2 B genes\*\*\*

**B-Thalassemia** 1. Thalassemia Intermedia

Two defective but **partially functional B genes** \*\*\*Severity is between Minor and Major\*\*\*

**B-Thalassemia** 1. Disease

Increased **RBC destruction** Iron (Fe) **overload** Anemia, hypermetabolic marrow Therapeutic **phlebotomy** (bleeding) _Transfusion Requirement_

**Sideroblastic Anemias** 1. Marrow Effects? 2. Iron Stores? 3. Cause

1. All sideroblastic anemias produce **ringed sideroblasts** in the marrow 2. Irone stores are sufficient, usually **high** 3. Not making **porphyrin**

Bone Marrow with **Ringed Sideroblasts**

**Sideroblastic Anemias** 1. Congenital 2. Acquired (primary vs secondary)

1. X-linked and involve **ALA synthase deficiency** 2. Primary (myelodysplastic syndrome - **pre-malignant**) Secondary (**alcohol abuse**, drug induced (isoniazid, chloramphenicol), **lead poisoning**, **copper deficiency**)

**Sideroblastic Anemias** 1. Characteristics

May be **normocytic** May have a **dimorphic appearance** May demonstrate **hemolytic changes** May show **iron deposits** (\*\*\*Pappenheimer Bodies\*\*\*) \*\*\*Transfusion to treat anemia, therapeutic phlebotomy to treat iron overload\*\*\*

**Pappeheimer Body** (precipitated iron granules)

**Sideroblastic Anemia** - Dimorphism - Hypochromic - Teardrop shapes

**Sideroblastic Anemia** 1. Summary 2. Treatment

1. Total body **iron overload**, insufficient heme iron 2. **Treated** with **Pyridoxine**, Transfusion, Phlebotomy, Chelation, Marrow Transplantation

Summary of Anemia Testing