RBC Disorders Flashcards
1
Q
Anemia
A
- reduction in circulating RBC mass
- presents with signs and sxs of hypoxia (weakness, fatigue, dyspnea, pale conjunctiva, pale skin, headache, lightheadedness, angina especially in preexisting CAD)
- hemoglobin (Hb), hematocrit (Hct), and RBC count are used as surrogates for RBC mass, which is difficult to measure
- anemia: 100 microm^3)
2
Q
Microcytic Anemias (Basic Principles)
A
- anemia with MCV < 80 microm^3
- microcytic anemias are due to dec production of Hb
- RBC progenitor cells in the bone marrow are large and normally divide multiple times to produce smaller mature cells (MCV = 80-100 microm^3)
- microcytosis is due to an “extra” division which occurs to maintain hemoglobin concentration
- hemoglobin is made of heme and globin; heme is composed of iron and protoporphyrin
- a decrease in any of these components leads to microcytic anemia
- microcytic anemias include iron deficiency anemia; anemia of chronic disease; sideroblastic anemia; thalassemia
3
Q
Iron Deficiency Anemia
A
- due to decreased levels of iron
- low iron –> low heme –> low Hb –> microcytic anemia
- most common type of anemia
- lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of world’s population
4
Q
Consumption of Iron
A
- iron is consumed in heme (meat-derived) and non-heme (vegetable-derived) forms
- 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
5
Q
Laboratory Measurements of Iron Status
A
- serum iron: measure of iron in the blood
- total iron-binding capacity (TIBC): measure of transferrin molecules in the blood
- % saturation: percentage of transferrin molecules that are bound by iron (normal is 33%)
- serum ferritin: reflects iron stores in macrophages and the liver
6
Q
Causes of Iron Deficiency
A
- 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 iron absorption by maintaining the Fe2+ state, which is more readily absorbed than Fe3+)
7
Q
Stages of Iron Deficiency
A
- storage iron is depleted: decreased ferritin and increased TIBC
- serum iron is depleted: decreased serum iron means decreased % saturation
- normocytic anemia: bone marrow makes fewer, but normal-sized, RBCs
- microcytic, hypochromic anemia: bone marrow makes smaller and fewer RBCs
8
Q
Clinical Features of Iron Deficiency Anemia
A
- anemia
- koilonychia (spoon nails)
- pica (appetite for substances that are largely non-nutritive like paper, clay, metal, etc.)
9
Q
Laboratory Findings in Iron Deficiency Anemia
A
- microcytic, hypochromic RBCs with increased red cell distribution width (RDW)
- dec ferritin; inc TIBC; dec serum iron; dec % saturation
- inc free erythrocyte protoporphyrin (FEP)
10
Q
Treatment for Iron Deficiency Anemia
A
-supplemental iron (ferrous sulfate)
11
Q
Plummer-Vinson syndrome
A
- iron deficiency anemia with esophageal web and atrophic glossitis
- presents as anemia, dysphagia, and beefy-red tongue
12
Q
Anemia of Chronic Disease
A
- anemia associated with chronic inflammation (e.g. endocarditis or autoimmune conditions) or cancer
- most common type of anemia in hospitalized pts
- chronic disease results in production of acute phase reactants from the liver, including hepcidin
- hepcidin sequesters iron in storage sites by limiting iron transfer from macrophages to erythroid precursors and suppressing EPO production; aim is to prevent bacteria from accessing iron, which is necessary for their survival
- decreased available iron leads to dec heme which leads to dec Hb which leads to microcytic anemia
13
Q
Laboratory Findings and Treatment in Anemia of Chronic Disease
A
- inc ferritin, dec TIBC, dec serum iron, dec % saturation
- inc free erythrocyte protoporphyrin (FEP)
- treatment involves addressing the underlying cause
14
Q
Sideroblastic Anemia
A
- anemia due to defective protoporphyrin synthesis
- dec protoporphyrin –> dec heme –> dec Hb –> microcytic anemia
- iron is transferred to erythroid precursors and enters the mitochondria to form heme
- if protoporphyrin is deficient, iron remains trapped in mitochondria
- iron-laden mitochondria form a ring around the nucleus of erythroid precursors; these cells are called ringed sideroblasts (hence, the term sideroblastic anemia)
- can be congenital or acquired
- congenital defect most commonly involves ALAS (rate-limiting enzyme)
- acquired causes include alcoholism (mitochondrial poison); lead poisoning (inhibits ALAD and ferrochelatase); and vitamin B6 deficiency (required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for TB)
15
Q
Synthesis of Protoporphyrin
A
- aminolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic acid (ALA) using vit. B6 as a cofactor (rate-limiting step)
- aminolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen
- additional rxns convert prophobilinogen to protoporphyrin
- Ferrochelatase attaches protoporphyrin to iron to make heme (final rxn; occurs in the mitochondria)
16
Q
Laboratory Findings for Sideroblastic Anemia
A
-inc ferritin, dec TIBC, inc serum iron, inc % saturation (iron-overloaded state)
17
Q
Thalassemia
A
- anemia due to dec synthesis of the globin chains of Hb
- dec globin –> dec Hb –> microcytic anemia
- inherited mutation; carriers are protected against Plasmodium falciparum malaria
- divided into alpha and beta-thalassemia based on dec production of alpha or beta globin chains
- normal types of hemoglobin are HbF (alpha2, gamma2), HbA (alpha2, beta2), and HbA2 (alpha2, sigma 2)
18
Q
alpha-Thalassemia
A
- usually due to gene deletion; normally, 4 alpha genes are present on chromosome 16
- one gene deleted: symptomatic
- two genes deleted: mild anemia with inc RBC count; cis deletion is associated with an increased risk of severe thalassemia in offspring
- cis deletion is when both deletions occur on the same chromosome; seen in Asians
- trans deletion is when one deletion occurs on each chromosone; seen in Africans, including African Americans
- three genes deleted: severe anemia; beta chains form tetramers (HbH) that damage RBCs; HbH is seen on electrophoresis
- four genes deleted: lethal in utero (hydrops fetalis); gamma chains form tetramers (Hb Barts) that damage RBCs; Hb Barts is seen on electrophoresis
19
Q
beta-Thalassemia
A
- usually due to gene mutations (point mutations in promotor or splicing sites); seen in individuals of African and Mediterranean descent
- two beta genes are present on chromosone 11; mutations result in absent (beta0) or diminished (beta+) production of the beta-globin chain
20
Q
beta-Thalassemia Minor
A
- beta-Thalassemia minor (beta/beta+) is the mildest form of disease and is usually asymptomatic with an increased RBC count
- microcytic, hypochromic RBCs and target cells are seen on blood smear
- hemoglobin electrophoresis shows slightly dec HbA with increased HbA2 and HbF
21
Q
beta-Thalassemia Major
A
- beta0/beta0
- the most severe form of disease and presents with severe anemia a few months after birth
- high HbF at birth is temporarily protective
- unpaired alpha chains precipitate and damage RBC membrane, resulting in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBCs by the spleen)
- massive erythroid hyperplasia ensues resulting in expansion of hematopoiesis into the skull (reactive bone formation leads to “crewcut” appearance on x-ray) and facial bones (chipmunk facies); extramedullary hematopoiesis with hepatoplenomegaly; and risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
- chronic transufsions are often necessary; leads to risk for secondary hemochromatosis
- smear shows microcytic, hypochromic RBCs with target cells and nucleated RBCs
- electrophoresis shows HbA2 and HbF with little or no HbA
22
Q
Macrocytic Anemia (Basic Principles)
A
- anemia with MCV > 100 microm^3
- most commonly due to folate or vit. B12 deficiency (megaloblastic anemia)
- folate and vit. B12 are necessary for synthesis of DNA precursors
- folate circulates in the serum as methyltetrahydrofolate (methyl THF); removal of the methyl group allows for participation in the synthesis of DNA precursors
- methyl group is transferred to vit. B12 (cobalamin)
- vit. B12 then transfers it to homocysteine, producing methionine
- lack of folate or vit. B12 impairs synthesis of DNA precursors
- impaired division and enlargement of RBC precursors leads to megaloblastic anemia
- impaired division of granulocytic precursors leads to hypersegmented neutrophils
- megaloblastic change is also seen in rapidly-dividing (e.g. intestinal) epithelial cells
- other causes of macrocytic anemia (without megaloblastic change) include alcoholism, liver disease, and drugs (e.g. 5-FU)
23
Q
Folate Deficiency
A
- dietary folate is obtained from green vegetables and some fruits and is absorbed in the jejunum
- folate deficiency develops within months, as body stores are minimal
- causes include poor diet (e.g. alcoholics and elderly), inc demand (e.g. pregnancy, cancer, and hemolytic anemia), and folate antagonists (e.g. methotrexate (cancer drug), which inhibits dihydrofolate reductase)
24
Q
Clinical and Laboratory Findings in Folate Deficiency
A
- macrocytic RBCs and hypersegmented neutrophils (>5 lobes)
- glossitis (swollen tongue, tongue appears smooth)
- dec serum folate
- inc serum homocysteine (increases risk for thrombosis)
- normal methylmalonic acid
