Flashcards in Ch5 - 2) Microcytic anemia Deck (103):
Microcytic anemias include
(1) iron deficiency anemia, (2) anemia of chronic disease, (3) sideroblastic anemia, and (4) thalassemia.
Iron deficiency anemia is due to?
decreased levels of iron -> dec heme -> dec hemoglobin —» microcytic anemia
What is the most common type of anemia?
iron deficiency anemia
What is the most common nutritional deficiency in the world?
Lack of iron, affecting roughly 1/3 of world's population
Iron is consumed in what forms?
heme (meat-derived) and non-heme (vegetable-derived) forms
Absorption of iron occurs in the?
duodenum, Enterocytes have heme and non-heme (DMT1) transporters; the heme form is more readily absorbed
How do enterocytes transport iron?
across the cell membrane into blood via ferroportin
How does transferrin transports iron?
in the blood and delivers it to liver and bone marrow macrophages for storage.
Stored intracellular iron is bound to what?
ferritin, which prevents iron from forming free radicals via the Fenton reaction
Laboratory measurements of iron status
1) serum iron 2)TIBC 3) % saturation 4) Serum ferritin
What does the serum iron measure?
Serum iron is a measure of iron in the blood
What does total iron-binding capacity (TIBC) measure?
transferrin molecules in the blood
What does % saturation of iron measure?
percentage of transferrin molecules that are bound by iron (normal is 33%)
What does serum ferritin measure?
reflects iron stores in macrophages and the liver
What is iron deficiency is usually caused by?
dietary lack or blood loss
What is iron deficiency is usually caused by in infants?
breast-feeding (human milk is low in iron)
What is iron deficiency is usually caused by in children?
What is iron deficiency is usually caused by in adults?
(20-50 years old)—peptic ulcer disease in males and menorrhagia or pregnancy in females
What is iron deficiency is usually caused by in elderly?
colon polyps/carcinoma in the Western world; hookworm (Ancylostoma duodenale and Nieator americanus) in the developing world
What are some other causes for iron deficiency?
malnutrition, malabsorption, and gastrectomy (acid aids iron absorption by maintaining the Fe2+ state, which is more readily absorbed
What are the stages of iron deficiency?
1. Storage iron is depleted— decreased serum ferritin; increased TIBC (transferrin) 2. Serum iron is depleted— dec serum iron; dec % saturation 3. Normocytic anemia—Bone marrow makes fewer, but normal-sized, RBCs 4. Microcytic, hypochromic anemia—Bone marrow makes smaller and fewer RBC's
The initial stage of iron deficiency results in what type of anemia?
normocytic anemia b/c the bone marrow's initial response is to make as many normal RBC's as possible
what are the clinical features of iron deficiency
anemia, koilonychia, and pica.
Laboratory findings for iron deficiency include?
microcytic, hypochromic RBCs with increased red cell distribution width increased RDW, 2. decreased ferritin; inc TIBC; dec serum iron; dec % saturation 3. inc Free erythrocyte protoporphyrin (FEP
What is FEP?
free erythrocyte protoporphoryin - decreased Fe means less protoporphorin is bound producing heme.
Why do you have increased RDW in iron deficiency?
initial response of bone marrow is to produce as many normal RBC's as possible, after the anemia progresses it produces small RBC's - varying sizes means increased RDW
What is RDW?
red blood cell distribution width, measures the spectrum of size of the RBC's
What does a low RDW mean?
all of the red blood cells have the same size
What does a high RDW mean?
RBC's have diffent sizes
What is the treatment for iron deficiency anemia?
involves supplemental iron (ferrous sulfate) - always ask why is the pt iron deficient
How does the size of the RBC and compare to a lymphocyte on a blood smear?
nucleus of the lymphocyte should represent the size of the RBC
What is Plummer-Vinson syndrome?
it is iron deficiency anemia with esophageal web and atrophic glossitis; presents with anemia, dysphagia, and beefy-red tongue
What is an esophogeal web?
some of the mucosa of the esophagous outfolds potentially creating a partial obstruction in the esophagus
What is anemia of chronic disease
Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune conditions) or cancer;
What is the most common type of anemia in hospitalized patients?
anemia of chronic disease
How is hepcidin related to chronic disease?
chronic disease results in production of acute phase reactants from the liver including hepcidin.
What does hepcidin do?
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.
How is anemia of chronic disease related to micrcytic anemia?
decreased availablity of iron —> decreased heme -> decreased hemoglobin -> microcytic anemia
What are the laboratory findings for anemia of chronic disease?
inc ferritin, dec TIBC, dec serum iron, dec % saturation, inc FEP
In anemia of chronic disease why is there increased ferritin?
in anemia of chronic disease there is an inability to use storage iron - storage iron builds up meaning ferritin goes up
Why is there a decrease in serum iron in anemia of chronic disease?
if the bone marrow cannot use the iron in the macrophages it will use the iron from the serum also decreasing % satuation
Why is there increased FEP in anemia of chronic disease?
decreased iron availability leads to free protoporphorin since Hb is composed of HEME and PROTOPORPHORIN
Is anemia of chronic classified as normocytic or microcytic?
in the early phase of anemia of chronic disease the pt first develops a normocytic anemia, as it becomes more severe the pt can go on to develop microcytic anemia
What is the treatment of anemia of chronic disease?
Treatment involves addressing the underlying cause, exogenous EPO is useful in a subset of patients, especially those with cancer.
What is sideoblastic anemia due to?
Anemia due to defective protoporphyrin synthesis
How does sideroblastic anemia lead to microcytic anemia?
decreased protoporphyrin -> dec hemoglobin -> microcytic anemia
Where are the reactions of the protoporphorin synthesis occuring?
in the progenitor cells of the red blood cells in the erythroblast
What is the first step in the production of protoporphorin
1. Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step).
What is the rate limiting step in the synthesis of protoporphorin?
SCoA -> ALA via ALAS with B6 as a cofactor
What happens after the rate limiting step in the synthesis of protoporphorin?
Aminolevulinic acid dehydrogenase (ALAD) converts ALA to porphobilinogen (Additional reactions convert porphobilinogen to protoporphyrin)
In the synthesis of protoporphorin what happens in the final reaction?
Ferrochelatase attaches protoporphyrin to iron to make heme (occurs in the mitochondria).
How is heme formed?
Iron is transferred to erythroid precursors and enters the mitochondria to form heme.
What happens if protoporphyrin is deficient?
iron remains trapped in mitochondria
What is seen when iron gets trapped in the mitochondria?
iron-laden mitochondria form a ring around the nucleus of erythroid precursors; these cells are called ringed sideroblasts (hence, the term sideroblastic anemia).
Where does sideroblastic anemia get its name?
The ring around the nucleus of erythroid precursors of iron laden mitochondria is called ringed sideroblasts
Is sideroblastic anemia congenital or acquired?
can be either congenital or acquired
Describe the congenital form of sideroblastic anemia?
most commonly involves ALAS (rate-limiting enzyme)
What are the acquired causes of sideroblastic anemia?
Alcoholism, Lead poisoning, Vitamin B6 deficiency
How can alcoholism lead to sideroblastic anemia?
How does lead poisoning lead to sideroblastic anemia?
inhibits ALAD and ferrochelatase
How does Vitamin B6 deficiency lead to sideroblastic anemia? This is most commonly seen as a side effect of what treatment?
required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for tuberculosis
In sideroblastic anemia why is there increased ferritin?
build up of iron in the erythroid precursor which dies and leaks iron -> consumed by bone marrow macrophages -> high stores of Fe (increased ferritin)
What are the laboratory findings for sideroblastic anemia?
inc ferritin, dec TIBC, inc serum iron, and inc % saturation
Why is there increased percent saturation in sideroblastic anemia?
its an iron overloaded state and results in leakage of iron into serum also increasing the percent saturation
How are hemachromatosis patients similar to sideroblastic anemia patients?
both are iron overloaded states - similar lab values
What is thalassemia?
Anemia due to decreased synthesis of the globin chains of hemoglobin
How is thalassemia related to microcytic anemia?
dec globin -> dec hemoglobin —> microcytic anemia
what is a characteristic of the carriers of thalasemia?
it is an inherited mutation; carriers are protected against Plasmodium falciparum malaria.
How is thalassemia divided?
into alpha and beta thalassemia based on decreased production of alpha or beta globin chains
Regarding microcytic anemia what are the normal lab findings?
Ferritin- normal, TIBC- 300pg/dL, Serum Iron- 100pg/dL, % Saturation- 33%
Regarding microcytic anemia what are the lab values for Iron Deficiency Anemia?
Ferritin- Low, TIBC- High, Serum Iron- Low, % Saturation- Low
Regarding microcytic anemia what are the lab values for Anemia of Chronic Disease?
Ferritin- High, TIBC- Low, Serum Iron- Low, % Saturation- Low
Regarding microcytic anemia what are the lab values for sideroblastic anemia?
Ferritin- High, TIBC- Low, Serum Iron- High, % Saturation- High
Regarding microcytic anemia what are the lab values for pregnancy and oral contraceptives?
TIBC- High, % Saturation- Low
What are the normal types of hemoglobin?
HbF (alpha and gamma), HbA (alpha and beta), and HbA2 (alpha and sigma)
What is alpha-Thalassemia usually due to?
gene deletion; normally, 4 alpha genes are present on chromosome 16.
In alpha thalassemia what are the symptoms when one gene is deleted?
In alpha thalassemia what are the symptoms when two genes are deleted?
mild anemia with increased RBC count; cis deletion is associated with an increased risk of severe thalassemia in offspring.
In alpha thalassemia what are the symptoms when cis deletion occurs?
it is when both deletions occur on the same chromosome; seen in Asians
In alpha thalassemia what are the symptoms when trans deletion occurs?
it is when one deletion occurs on each chromosome; seen in Africans, including African Americans
Which is worse cis or trans deletion in alpha thalassemia?
Cis because it is associated with an increased risk of severe thalassemia in offspring
In alpha thalassemia what are the symptoms when three genes are deleted?
severe anemia; beta chains form tetramers (HbH) that damage RBCs; HbH is seen on electrophoresis.
In alpha thalassemia what are the symptoms when four genes are deleted?
lethal in utero (hydrops fetalis); gamma chains form tetramers (Hb Barts) that damage RBCs; Hb Barts is seen on electrophoresis.
What is Hb Barts?
it is a tetramer of gamma chains
What is the difference between beta and alpha thalassemia?
alpha is due to gene deletions and beta is due to gene mutations
Beta-Thalassemia is usually due what?
to gene mutations (point mutations in promoter or splicing sites); seen in individuals of African and Mediterranean descent
Where are beta genes present?
Two beta genes are present on chromosome 11; mutations result in absent (ß0) or diminished (ß+) production of the ß-globin chain
What is the difference between beta0/beta+?
beta0 is the complete inability to produce beta chain, beta+ is decreased production of beta chain
(beta/beta+ - one normal beta and one decreased production of beta) is the mildest form of disease and is usually asymptomatic with an increased RBC count.
In beta-thalassemia minor, what is seen on blood smear?
microcytic, hypochromic RBCs and target cells are seen on blood smear
In beta-thalassemia minor, what is seen on hemoglobin electrophoresis?
It shows slightly decreased HbA with increased HbA2 (5%, normal 2.5%) and HbF (2%, normal 1%)
(beta0/beta0) is the most severe form of disease and
How does beta-Thalassemia major present?
with severe anemia a few months after birth; high HbF (a2y2) at birth is temporarily protective
In beta-Thalassemia major, why is there ineffective erythropoiesis and extravascular hemolysis?
alpha tetramers aggregate and damage RBCs, (removal of circulating RBCs by the spleen).
What is ineffective erythropoesis in beta-Thalassemia major?
damage to the red blood cells as they are being generated by alpha dimers
What is extravascular hemolysis in beta-Thalassemia major?
removal of circulating RBCs by the spleen
Why do the patients with beta-Thalassemia major develop massive erythroid hyperplasia?
due to the anemia that develops
Why is there expansion of hematopoiesis into the skull in beta-Thalassemia major?
There is severe anemia resulting in erythropoietin increase from the kidney resulting in hyperplasia at the bone marrow
What does expansion of hematopoiesis in beta-Thalassemia major present as?
reactive bone formation leads to crewcut appearance on x-ray and facial bones chipmunk face
In beta-Thalassemia, what is seen in massive erythroid hyperplasia?
(1) expansion of hematopoeisis into marrow of the skull and facial bones (2) extra medullary hematopoiesis with hepatosplenomegaly, and (3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors.
In beta-Thalassemia what is often necessary?
chronic transfusions are often necessary; leads to risk for secondary hemochromatosis
In beta-Thalassemia, what does the blood smear show?
microcytic, hypochromic RBCs with target cells and nucleated red blood cells