RBC Disorders Flashcards
Anemia definition and symptoms
Reduction in Circulating RBC mass. Hb Below 13.5g/dL in Males and 12.5 g/dL in females
See symptoms of hypoxia = weakness, fatigue, dyspnea, pale conjunctiva and skin, headache/lightheaded, angina
Normal Lab values for Hemoglobin for Males and Females
Males = 13.5-17.5 g/dL Females = 12.5-16 g/dL
Microcytic vs Normocytic vs Macrocystic
Microcytic = MCV < 80 μm3 normocytic = MCV 80-100μm3 Macrocytic = MCV > 100μm3
Mechanism of Microcytic Anemias
Hb = heme (made of fe and protoporphyrin) + globin
Hb therefore decreases if any of the components decrease
Fe decreases with decreases intake, excess loss, or chronic disease. Protoporphyrin decreases with defects in its synthesis. Globin decreases in thalssemias
Become microcytic because bone marrow does one “extra” division to try and maintain Hb concentration
Normal pathway of Fe
Iron is consumed in heme (meat) and non-heme (veggies)
1) absoprtion occurs in duodenum’s enterocytes via DMT1 transporters (heme form is more readily absobred)
2) Enterocytes transport Fe across cell into blood via ferroportin
3) Transferrin picks up Fe in blood and carries it to liver and bone marrow macrophages for storage
4) Ferritin binds Fe intracellulary to store it and prevent it from forming free radicals
Laboratory measurements of Iron Status
1) Serum iron
2) Total Iron Binding Capacity
3) %Saturation
4) Serum Ferritin
1) Serum iron = meausre of Fe in blood
2) Total Iron Binding Capacity = measure of transferrin molecules in blood
3) %Saturation = percentage of transferrin binding a Fe (normally 33%)
4) Serum Ferritin = reflects Fe reserves in macrophages and liver
Causes of Iron deficiency
1) Infants - breast milk has low Fe
2) Children - poor diet
3) Adult males = peptic ulcer
4) Adult females = menorrhagia
5) Elederly = colon polyps / carcinoma
6) Hookwork infections = Ancyostoma duodenale and Nector Americanus
7) Malnutirition or malabsorption (celiac)
8) Gastrectomy = acid normally aids absorption of Fe by keeping it in 2+ state which is transported easier than 3+
Stages of Iron Deficiency and sumamry lab values
1) Storage of Fe is depleted - ↓ ferritin, ↑ TIBC
2) Serum Fe is depleted = ↓ serum iron, ↓%saturation
3) Normocytic Anemia = EARLY STAGE bone marrow makes fewer but normal sized RBCs
4) Microcytic, hypochromic Anemia = Bone marrow makes fewer and smaller RBCs.
Labs: microcytic, hypochromic RBS with ↑Red cell distribution Width (RDW = lots of different sized RBCs)
↓ ferritin, ↑ TIBC, ↓ serum iron, ↓%saturation
Treat with supplemental Fe (ferrous sulfate) and treat underlying condition
Plummer Vinson Syndrome
Iron deficiency Anemia with esophageal web and atrophic glossitis. Anemia, dysphagia, and beefy red tongue.
Anemia of Chronic Disease
- Mechanism
- Labs
Associated with chronic inflammation or cancer. Chronic disease get acute phase reactants from liver including hepcidin. Hepcidin sequesters Fe storage by (1) limiting iron transfer from macrophages to to erthyroid precursors (2) suppressing Erythropoietin; aim is to prevent bacteria access to Fe.
↓ available Fe, ↓ heme, ↓hemeglobin, normocytic, to microcytic
↑ferritin, ↓TIBC, ↓serum iron, ↑%saturation, ↑Free erythrocyte protoporphyrin
Hepcidin
Acute phase reactant produced by liver. It sequesters Fe storage by (1) limiting iron transfer from macrophages to to erthyroid precursors (2) suppressing Erythropoietin; aim is to prevent bacteria access to Fe. Responisble for anemia seen in chronic disease
Sideroblastic Anemia
Microcytic Anemia due to defective protoporphoryin synthesis characterized by ringed sideroblasts on histology (iron trapped in mitchondira surround nucleus of erythroid precursors)
Fe enters erythroblasts’s mitochondria, no protoporphyrin to attach to, Fe causes free radicals and damages cell, cell dies and releases Fe into serum, Some Fe is taken up by bone macrophages (↑ferritin)
See ↑ferritin, ↓TIBC, ↑serum iron, ↑%saturation = iron overloaded state.
Steps of Protoporphyrin Synthesis
1) Aminovulenic Acid synthetase (ALAS) converts Succinyl CoA to Aminolevulinic Acid (ALA) using B6 as a cofactor. Rate limiting step
2)Aminovulenic Acid Dehydratase (ALAD) converts ALA to porphobilinogen
3) Series of reactions converts porphobilinogen to protoporphyrin
4)Ferrocheletase INSIDE mitochondria attaches Fe to protoporphyrin to make Heme
A defect in any step will cause Fe to be trapped in the mitochondira and give rise to “ringed sideroblasts” and give sideroblastic anemia
Ringed Sideroblasts
Cells with Iron ladden mitochondria surrounding nucleus. Due to problems with protoporphyrin synthesis and sign of Sideroblastic Anemia
Congenital Defects of Sideroblastic Anemia
Deficiency in any of the enzymes needed to make protoporphyrin.
Most commonly seen is defect in ALAS that converts SCoA to ALA
Acquired Causes of Sideroblastic Anemia
Alcoholism - poisons mitochondria and impairs production of protoporphyrin
Lead Poisoning = inhibits ALAD and Ferrocheletase
Vitamin B6 deficiency = required cofactor for ALAS (most commonly seen in isoniazid treatment for TB)
Isoniazid
Drug used in treatment of TB. Side effect is Vitamin B6 deficiency that leads to siderblastic anemia
Thalsassemia
Microcytic anemia due to decreased synthesis of globin chains
Inherited mutations. Carriers are protected against plasmodium falciprum
Normal types of Hemeglobin
Fetal = HbF = α2γ2 HbA = α2β2 HbA2 = α2δ2
αThalsassemias
-all variations and ethnicities
Gene DELETION.
Normally 4 α genes, 2 each on chromosomes 16
(1)One deletion = asymptomatic
(2)Two Deleted = mild anemia with increased RBC count
Cis = ASIAN. deletions occur on same chromosomes and more liekly to produce severely anemic children
Trans = AFRICAN. Deletions on opposite chromosomes
(3) Three genes deleted = severe anemia. β chains form tetramers (HbH) that damages RBCs
(4) 4 genes deleted = hydrops fetals = lethal in utero. γ chains for tetramers (Hb Barts) that damage RBCs
β Thalassemia
Gene MUTATION seen in Africans and Mediterraneans
Two β genes on chromosome 11. Mutations result in absent β0 or diminished β+ production of β chain.
Get microcytic anemia with varying severity depending on mutations
β Thalassemia minor
β/β+ = mildest form of disease. Usually asymptomatic with slight increase in RBC count
Get microcytic, hypochromic RBCs, and traget cells on blood smear
Slightly decreased HbA and increased HbA2 and HbF
β Thalassemia Major
β0/β0. Most severe form of disease seen few months after birth since HbF is initially protective
α tetramers aggregate and damage RBC resulting in effective erythropoiesis and extravascualr hemolysis (removal of RBCs by spleen).
Get massive Erythroid hyperplasia ensues and see (1)hematopoiesis occuring not just in central axilia skeleton but also in skull (buzzcut appearance on xray) and facial bones (chipmunk facies) (2) extramedullary hematopoiesis (liver and spleen) (3) risk for aplastic crisis with parvovirus B19 infection of erythroid precursors.
Need chronic transfusions that can lead to sexondary hemochromatosis
Smear shows microcytic, hypochromic RBCs, target cells, nucleated RBCs.
Have HbA2 and HbF, and little to no HbA
Crewcut appearance on X-ray and Chipmunk Facies
β Thalassemia Major