RBC disorders Flashcards
What is Anemia
Reduction in circulating red blood cell (RBC) mass
Anemia generally presents with
Weakness, fatigue, and dyspnea 2. Pale conjunctiva and skin 3. Headache and light headedness 4. Angina, especially with preexisting coronary artery disease
Anemia labs
Anemia is defined as Hb < 13.5 g/dL in males and< 12.5 g/dL in females
normal Hb is 13.5-17.5 g/dL in males and 12.5-16.0 g/dL in females
MCV classification of anemia
anemia can be classified as microcytic
(MCV < 80 µm3), normocytic (MCV = 80-100 µm3), or macrocytic (MCV > 100 µm3).
Basic Principles of Microcytic Anemias
Anemia with MCV < 80 µm3
B. Microcytic anemias are due to decreased production of hemoglobin.
1. RBC progenitor cells in the bone marrow are large and normally divide multiple
times to produce smaller mature cells (MCV = 80-100 µm3). 2. Microcytosis is due to an “extra” division which occurs to maintain hemoglobin
concentration.
C. Hemoglobin is made of heme and glob in; heme is composed of iron and
protoporphyrin. A decrease in any of these components leads to microcytic anemia. D. Microcytic anemias include (1) iron deficiency anemia, (2) anemia of chronic
disease, (3) sideroblastic anemia, and (4) thalassemia.
Iron Deficiency Anemia lab measures
Serum iron-measure of iron in the blood
2. Total iron-binding capacity (TIBC) - measure of transferrin molecules in the
blood 3. % saturation - percentage of transferrin molecules that are bound by iron
(normal is 33%) 4. Serum ferritin - reflects iron stores in macrophages and the liver
Pathology of Iron Deficiency Anemia
Due to decreased levels of iron
1. ↓i ron →↓heme → ↓hemoglobin → m
icrocytic anemia
B. Most common type of anemia
1. Lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of world’s population.
Iron is consumed in heme (meat-derived) and non-heme (vegetable-derived) forms.
1. Absorption occurs in the duodenum. Enterocytes have heme and non-heme (DMT1) transporters; the heme form is more readily absorbed.
- Enterocytes transport iron across the cell membrane into blood via ferroportin.
- Transferrin transports iron in the blood and delivers it to liver and bone marrow macrophages for storage.
- Stored intracellular iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction.
Causes of Iron Deficiency Anemia
- Infants - breast-feeding (human milk is low in iron)
- Children-poor diet
- Adults (20-50 years) - peptic ulcer disease in males and menorrhagia or pregnancy in females
- Elderly - colon polyps/carcinoma in the Western world; hookworm
(Ancylostoma duodenale and Necator americanus) in the developing world - Other causes include malnutrition, malabsorption, and gastrectomy (acid aids than Fe 3+).iron absorption by
Stages of Iron deficiency
- Storage iron is depleted - ↓ferritin; ↑TIBC
- Serum iron is depleted - ↓serum iron; ↓% saturation
- Normocytic anemia - Bone marrow makes fewer, but normal-sized, RBCs.
- Microcytic, hypochromic anemia - Bone marrow makes smaller and fewer RBCs.
clinical features of iron deficiency anemia
Clinical features of iron deficiency include anemia, koilonychia, and pica
lab findings of iron deficiency anemia
- Microcytic, hypochromic RBCs with ↑red cell distribution width (RDW)
- ↓ferritin; ↑TIBC; ↓ serum iron; ↓% saturation
- ↑Free erythrocyte protoporphyrin (FEP)
Treatment for Iron deficiency anemia
Treatment involves supplemental iron (ferrous sulfate)
Plummer-Vinson syndrome
Plummer-Vinson syndrome is iron deficiency anemia with esophageal web and
atrophic glossitis; presents as anemia, dysphagia, and beefy-red tongue
Anemia of Chronic Disease
Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune
conditions) or cancer; most common type of anemia in hospitalized patients
Pathology of iron deficiency anemia
Chronic disease results in production of acute phase reactants from the liver,
including hepcidin.
1. Hepcidin sequesters iron in storage sites by
(1) limiting iron transfer from
macrophages to erythroid precursors and
(2) suppressing erythropoietin (EPO) production; aim is to prevent bacteria from accessing iron, which is necessary for their survival.
decrease iron - decrease heme- decrease hemoglobin - microcytic
Lab findings of Anemia of Chronic Disease
↑ ferritin, TIBC, serum iron, and % saturation
2. ↑ Free erythrocyte protoporphyrin (FEP)
Treatment for Anemia of chronic disease
Treatment involves addressing the underlying cause.
Sideroblastic Anemia
Anemia due to defective protoporphyrin synthesis
1. protoporphyrin heme hemoglobin microcyt ic anemia
Protoporphyrin is synthesized via a series of reactions…
- Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to
aminolevulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step). - Aminolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen.
- Additional reactions convert porphobilinogen to protoporphyrin.
- Ferrochelatase attaches protoporphyrin to iron to make heme (final reaction; occurs in the mitochondria)
What happens to iron in sideroblastic anemia
Iron is transferred to erythroid precursors and enters the mitochondria to form
heme. If protoporphyrin is deficient, iron remains trapped in mitochondria.
1. Iron-laden mitochondria form a ring around the nucleus of erythroid precursors;
these cells are called ringed sideroblasts (hence, the term sideroblastic anemia, Fig. 5.2).
congenital vs acquired sideroblastic anemia
Sideroblastic anemia can be congenital or acquired.
1. Congenital defect most commonly involves ALAS (rate-limiting enzyme).
- Acquired causes include
i. Alcoholism - mitochondrial poison ii. Lead poisoning - inhibits ALAD and ferrochelatase iii. Vitamin B6 deficiency - required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for tuberculosis
lab findings for sideroblastic anemia
Laboratory findings include increased ferritin , decreased TIBC, increased serum iron, and increased % saturation
(iron-overloaded state).
Thalassemia
A. Anemia due to decreased synthesis o f the glob in chains of hemoglobin
1. ⬇️globin- ⬇️hemoglobin ➡️microcytic anemia
B. Inherited mutation; carriers are protected against Plasmodium falciparum malaria. C. Divided into - and -thalassemia based on decreased production of alpha or beta
globin chains.
1. Normal types of hemoglobin are HbF ( 2 2) , HbA ( 2 2) , and HbA 2 ( 2 2).
compare lab findings for microcytic anemias