Heme II Chapter 7 & 8

Most total body iron is present as what?

hemoglobin iron (affects RBC capacity to carry O2)

Stored ferritin iron

easily utilized by body

Stored serum ferritin

measures iron stores

Transferrin role in iron regulation

transport, 2 iron binding sites

Ferritin role in iron regulation

iron storage

Ferroportin role in iron regulation

transports iron across membranes

Hemosiderin role in iron regulation

iron storage, less available

Hephaestin role in iron regulation

Cu dependent enzyme that helps iron across enterocyte membrane.

Hepcidin role in iron regulation

inactivates ferroportin, decreases iron absorption

Adult male normal iron levels

Serum 65-170 mcg/dL

TIBC 250-450 mcg/dL

Transferrin 200-400

% Transferrin Saturation 20-55

Ferritin 20-250

Adult female normal iron levels

Serum 50-170 mcg/dL

TIBC 250-450 mcg/dL

Transferrin 200-400

% Transferrin Saturation 15-50

Ferritin 10-120

Newborn normal iron levels

Serum 40-250 mcg/dL

TIBC 100-400 mcg/dL

Transferrin 130-275

% Transferrin Saturation 12-50

Ferritin 50-600

Adolescent normal iron levels

Serum 50-150 mcg/dL

TIBC 250-450 mcg/dL

Transferrin 200-400

% Transferrin Saturation 15-55

Ferritin 10-150

Sources of Iron

meat, fish, green veggies, wheat germ, cereals (wheaties), beans, whole grain breads

What form of iron is incorporated within the heme moiety competing the lasts tem of heme biosynthesis?

ferrous (Fe2+)

Microcytic anemia

MCV < 80

MCHC < 32

serum iron, total iron binding capacity (TIBC), ferritin

Microcytic anemia low iron

iron deficiency

anemia or chronic inflammation

renal disease

Male anemia

<13 g/dl

Female anemia

<12 g/dl

Microcytic

Thalassemia

Iron deficiency

Chronic disease

Sideroblastic

Lead poisoning

Normocytic

Renal disease

Acute blood loss

Chronic disease

Hemolysis

Macrocytic

B12 deficiency

Liver disease

ETOH

Folate

Drugs/dysplasia

Microcytic hypochromic anemias

Involves a defect in hemoglobin synthesis

Iron Deficiency Anemia

Low iron, low hgb

Not enough in or too much out (find leak)

1st step – rule out bleeding

High risk

• Prenatal

• Children

Etiology

• Inadequate intake

• Increased need

• Impaired absorption

• Chronic blood loss

Stage 1 of IDA

progressive loss of storage iron

• normal iron, normal hgb, normal TIBC, ↓ ferritin,

  normal % saturation, normal morph

Stage 2 of IDA

exhaustion of iron storage pool

• ↓ iron, slight ↓ hgb, ↑ TIBC, ↓ ferritin, ↓ % saturation,

  slight micro/hypo

Stage 3 IDA

anemia

• Same as stage 2, but more pronounced

• ↓ ↓ ↓ hgb, marked micro/hypo

Signs and Symptoms of IDA

Fatigue, Irritability, Headache, Weakness, especially with exercise, Shortness of breath, Tachycardia, Pale skin color or pallor

Koilonychias

severe IDA

concave, cracked nails

Glossitis

severe IDA

sore, swollen tongue

PICA

Severe IDA

urge to eat non food things

Laboratory Findings of IDA

Microcytic, hypochromic

↓ Hgb, MCV, iron, ferritin, % saturation

↑ RDW, TIBC, transferrin

Iron deficiency anemia treatment- Oral supplements

Ferrous sulfate, Iron dextran parenteral administration, Monoferric – given IV

Iron deficiency anemia treatment- RBC transfusion

does not fix Fe def

Anemia of Chronic Inflammation etiology

2nd most common cause of anemia

Due to a chronic conditions/infections

Hospitalized patients

Autoimmune

Long term immune activation

High levels of hepcidin (acute phase reactant

Laboratory testing and results (ACI)

RBCs may be microcytic to normocytic and hypochromic to normochromic

Unremarkable morphology

↓ serum iron – it’s all hiding, transferrin, % saturation, and TIBC

 Norm-↑ ferritin and transferrin – knows iron is hiding

Differential diagnosis between IDA and anemia of inflammation

Transferrin decreased in ACI

Sideroblastic Anemias

Defective incorporation of iron into hemoglobin

• present but cannot be used, accumulation in erythroid cells, ineffective erythropoiesis, increase in serum and tissue iron, microcytic/hypochromic

iron deposits in mitochondria of erythroblasts

Ringed sideroblasts in bone marrow are HALLMARK

Sideroblastic Anemias

congenital- rare

acquired- myelodysplastic syndrome with ringed syderoblasts in BM

secondary- lead (rare), blocks heme synthesis, basophilic stippling (ribosomes), no ringed sideroplasts

alcohol/ drugs

Sideroblastic Anemia Laboratory Findings

ringed sideroblasts ONLY in BM

• Fe accumulation in mitochondria (dots around nucleus)

↓ Hgb and RBC

Dimorphic RBCs

Variable MCV and MCH

↑ RDW

Anisocytosis, poikilocytosis, target cells, Pappenheimer bodies, and basophilic stippling.

Serum

• ↑ iron, ferritin, % saturation

• Normal - ↓ Transferrin/TIBC

Treatment for Sideroblastic Anemia

Pyridoxine (B6)

Transfusion

The Porphyrias

Hereditary conditions that impair production of protoporphyrin in the heme synthesis pathway

Disorders of iron storage

Inability to convert porphyrins into protoporphyrin and then heme

• defective enzymes causes excess iron in the tissues

Iron overload and hemochromatosis

• accumulation of excess iron in cells in various tissues

• hemochromatosis

Hemochromatosis

tissue damage resulting from excess iron

Hereditary hemochromatosis (HH)

Recessive genetic disorder

Hepcidin deficiency

• Exessive accumulation of iron

Leads to chronic liver disease, arthritis, diabetes,

pituitary damage, congestive cardiac failure, and cardiac arrhythmias.

Secondary hemochromatosis can be acquired or

secondary to other inherited hemolytic anemias.

Anemia

Ineffective erythropoiesis

Iron overload

Early clinical findings of HH

Nonspecific and may include fatigue, joint pain, bronze discoloration of the skin

Laboratory testing and results of HH

Increased liver function enzyme tests

If due to Hereditary hemochromatosis

• ↑ serum iron, serum ferritin, serum transferrin

Treatment for HH

Therapeutic phlebotomy

chelating agents may be used to reduce iron stores

Macrocytic anemia

MCV > 103

B12 and folate levels

Etiology of Megaloblastic Anemia

Root Cause

• impaired DNA synthesis (not RNA)

• defective nuclear maturation

Deficiencies of vitamin B12 and/or folate

anemia is mild to severe

Vitamin B12

AKA cobalamin (cobalt + vitamin)

essential nutrient present in foods of animal irigin

nutritional deficiency uncommon

Decreased B12 usually accompanied by?

increased folate

Major cause of B12 deficiency is?

malabsorption- pernicious anemia

B12 Deficiency Causes

Dietary deficiency: vegan diet

Malabsorption

hemodialysis

HIV/AIDS

alcohol

Role of Vitamin B12

RBC maturation in BM

energy levels

brain and nerve health (myelin synthesis)

DNA synthesis

converts methylmalonyl CoA to Succinyl CoA

Vitamin B12 DNA synthesis

Breaks down homocysteine into methionine

Transfer of a methyl group from 5-methyltetrahydrofolate (5-methyl THF) to homocysteine, generating methionine

Pancytopenia

low RBC, WBC and platelets

T/F Ineffective erythropoiesis is exhibited in Megaloblastic anemia

True

Folate Function

transfers carbon units in the form of methyl groups from donors to receptors

Folate Deficiency

leads to impaired cell replication

Folate Circulates in the blood as?

5-methyl Tetrahydrofolate

Folate is found in what?

Green leafy veggies, fruits, dairy, cereals, animal foods

Causes of folic acid deficiency

Decreased dietary intake

Increased requirement

Malabsorption

Drug-induced - methotrexate, pyrimethamine, phenytoin, alcohol, isoniazid, and oral contraceptives

The most common causes of folate malabsorption are diseases of the intestinal tract.

Clinical manifestations of folic acid deficiency are the same as those for vitamin B12 deficiency

nerve damage

depression

dementia

Role of Folate and Vitamin B12

folate carries methyl group

B12 helps deliver the methyl group to homocysteine so it can become methionine

FOLATE PROVIDES B12 TRANSFERS

Without B12 what happens to folate?

its trapped as 5-methyl-THF and can’t be used causing increased homocysteine and impaired DNA synthesis

Final goal of Vitamin B12 and Folate

DNA synthesis

Pernicious Anemia

Autoimmune Disorder

CD4 T cells attack parietal cells, interfere with IF secretion

Intestinal malabsorption of B12 due to lack of intrinsic factor

Production of antibodies to IF and gastric parietal cells (B23 absorption blocked)

Glossitis

inflammation of the tongue that causes it to swell, turn red, and often become smooth and sore

Pernicious anemia refers to cobalamin deficiency that results from lack of what?

Intrinsic factor