5: Red Blood Cell Disorders Flashcards
Anemia is defined as (values)
Classified based on MCV as
Hgb <13.5 g/dl in males and <12.5 g/dl in females
Microcytic <80 um3
Normocytic 80-100
Macrocytic >100
Why are RBCs small in microcytic anemia?
Decreased production of hemoglobin -> extra division (leading to smaller cells) to maintain Hgb concentration
Composition of hemoglobin?
Based on these, what are the 4 causes of microcytic anemia?
Hemoglobin = heme + globin Heme = iron + protoporphyrin
iron deficiency anemia - low iron
anemia of chronic disease - Fe not available due to inc storage in macrophages
sideroblastic anemia - low protoporphyrin
thalassemia - low globin
What is the most common type of anemia
Iron deficiency anemia - roughly 1/3 of world population
Absorption of iron: source? absorbed where? transportation, storage?
Consumed in heme (meat-derived, more readily absorbed) and non-heme (vegetable-derived) forms
Absorption occurs in duodenum, where enterocytes have DMT1 transporters
Transported across CM into blood via ferroportin
Transported in blood via transferrin, delivered to liver, bone marrow macrophages for storage
Stored, bound to ferritin
This prevents iron from forming free radicals via Fenton reaction
Physiologically, there is really no way to eliminate iron in the body, so in absorption, enterocyte has to decide if it will go to the blood (via ferroportin)
Lab measures of iron status (4)
Serum iron
Total iron-binding capacity (TIBC) - serum transferrin, bound or unbound
% saturation - normal is 33%; for every 3 transferrin, one is bound to Fe
Serrum ferritin - reflects iron stores in macrophages and liver
Common causes of IDA in different populations (infant, children, adults, elderly) and other conditions (3)
Infant - breast milk is low in iron
Children - poor diet
Adults - PUD (males), pregnancy, menorrhagia (females)
Elderly - colon polyps/ca; hookworm (Ancylostoma duodenale and Necator americanus) in developing
Other - malnutrition, malabsorption (ex. celiac disease destroys microvilli in duodenum), gastrectomy (acid maintains Fe2+ state, more readily absorbed vs Fe3+; “Fe2 goes IN2 the body”)
Stages of iron deficiency (4) Clinical features (3)
Level of FEP/Free erythrocyte protoporphyrin?
Storage Fe depleted (low ferritin, high TIBC - always opposite, think like more transferrin to find more irons)
Serum Fe depleted (low serum Fe, low saturation)
Normocytic anemia first! - production of fewer, but normal sized RBCs
Microcytic, hypochromic anemia (with high RDW - big spectrum of size between RBCs kasi may normocytic and may microcytic)
Anemia
Koilonychia
Pica
High FEP (Heme = Fe + protoporphyrin)
Treatment of IDA
Supplemental iron (ferrous sulfate) + treat underlying cause
A syndrome associated with IDA is called Plummer-Vinson syndrome. Characteristics?
Esophageal webs, atrophic glossitis
Presents with dysphagia (from esophageal webs), beefy-red tongue (from glossitis - atrophy of lingual papillae), anemia
Anemia of chronic disease is associated with chronic inflammation (like endocarditis or autoimmune disease) or cancer.
This results in production of acute phase reactants from the liver. Which of these is important for ACD and how does it cause anemia?
Hepcidin sequesters iron in storage sites
(Body sort of hides iron which is needed by bacteria)
by:
1) limiting iron transfer from macrophages to erythroid precursors, and
2) suppressing erythropoietin (EPO) production
Anemia of chronic disease is associated with chronic inflammation (like endocarditis or autoimmune disease) or cancer.
Lab findings in terms of iron studies and FEP?
High ferritin (storage Fe can’t be used)
Low transferrin (opposite)
Low serum iron (since body can’t use stored iron, it uses serum Fe instead)
Low saturation
High FEP (inaccessible Fe so body won’t make Heme, Heme = Fe + proto)
Anemia of chronic disease is associated with chronic inflammation (like endocarditis or autoimmune disease) or cancer.
Treatment?
Treat underlying cause
Exogenous EPO useful in some populations, esp those with cancer
Sideroblastic anemia is due to defective protoporphyrin synthesis.
What is the process of protoporphyrin formation? (4 ish)
Succinyl CoA converted to ALA via ALAS with Vit B6 cofactor (rate-limiting step)
ALA converted to porphobilinogen via ALAD
Porphobilinogen converted to protoporphyrin via series of reactions…
Protoporphyrin bound to Fe via Ferrochelatase, to produce Heme. This final reaction occurs in the mitochondria.
Sideroblastic anemia is due to defective protoporphyrin synthesis.
Why is this anemia associated with ringed sideroblasts with Prussian blue stain?
Protoporphyrin deficiency -> Iron not used and remains trapped in mitochondria which forms a ring around the nucleus of erythroid precursors
