Flashcards in Module 1: Thalassemia and Iron deficiency Anemia Deck (34):
Starting off with the microcytic hemolytic anemias is Alpha Thalassemia, what is the etiology of this?
Deletion mutations on chromosome 16 to any number of the 4 alpha globin genes, which leads to decreased synthesis of alpha globin and accumulation of unpaired Beta globin chains
What are the four different types of Alpha Thalassemia?
1. Silent Carrier: 1 alpha gene deleted (Asymptomatic)
2. Alpha thalassemia trait: Two genes deleted
--- alpha/alpha and -/- (SE Asian) CIS
--- alpha/- and alpha/- (African) TRANS
---mild anemia with increased RBC count
3. Hemoglobin Hd: 3 genes affected; severe anemia
---B chain form tetramer (HbH) --- high affinity O2 -- severe tissue hypoxia
---HbH is prone to oxidation -- precipitated inclusions in older RBCs --- extravascular hemolysis
4. Hydrops Fetalis= lethal in utero; 4 genes deleted
--gamma chains form tetramers (Hb Barts) -- extremely high affinity for 02 --- no O2 reaches tissues
The next hypochromic microcytic anemia is Beta Thalassemia, with extravascular hemolysis. What is the etiology of this anemia?
Decreased synthesis of structurally normal beta globin chains due to point mutations in chromosome 11 in promotor or splicing sites
Inadequate levels of B-globin leads to what?
unpaired alpha globin chains
Explain B+ and B0
B+ : decreased beta chains produced -- mutation in promotor region of gene
B0: no beta chains (homozygous)-mutation in splicing or chain termination
What types of ppl get beta thalassemia?
Mediterranean and S.E. asian males
There are two types of Beta thalassemia, what are these types?
Minor or Trait: B0/B or B+/B -- mild asymptomatic anemia (one normal beta chain and one dimished (+) or absent (0) )
Major: B0/B0 or B+/B+ --- severe transfusion dependent anemia (Abnormal in causes occlusion in small blood vessels)(no beta chains period)
As mentioned before beta thalassemia major is predominately extravascular hemolysis, so therefore what signs will you see in the patient?
Splenomegaly (again this is happening in the spleen) causing a dragging pain in the LUQ
Chronic Hemolytic Anemia (spleen is destroying the RBCs)
---splenic macrophages are eating the defective RBC causing splenomegaly
Beta thalassemia major also involves extramedullary hematopoiesis, what does this involve?
Eventually the liver and spleen starts compensating for the lysing and decreased RBC so more hematopoietic cells are made causing hepatosplenomegaly.
--also causes lymphadenopathy
Patient with beta thalassemia major also have frontal bossing seen on examination (called crew cut appearance on xray) and chipmunk faces, what is this due to?
Expansion of the hematopoietic marrow in the skull via two mechanisms:
Intramedullary hematopoiesis (erythroid hyperplasia): Bone marrow is making more reticulocytes due to increased destruction of RBCs.
Intramedullary hemolysis (aka ineffective erythropoiesis): alpha chain tetramers break RBCs before they leave the marrow.
What are other signs and symptoms in a patient with beta thalassemia?
Jaundice (Due to the unconjugated bilirubin)
Failure to thrive in small kids
Electrophoresis is the best investigation for beta thalassemia, what is seen?
Major: very prominent HbF and small amount of HbA2 (if B0/B0 then no HbA at all; if B+/B+ then a very small amount of HbA)
Minor: HbA2 small amount, small amount of HbF and still majority HbA
What do you see on peripheral blood smear in a patient with thalassemia major?
--Anisopoikilocytosis (RBCs of different shapes and sizes) causes an increase in RDW
---Reticulocytosis (Due to the intramedullary hematopoiesis)
---Target cells ( Hb settling in the center of the cell)
---Normoblasts (due to the Intramedullary hemolysis )
--Hypochromic microcytic RBCs (decreased MCHC due to decreased Hb and decreased MCV)
--Howell Jolly Bodies (because the spleen is getting over worked)
What is seen in regards to lab values in these patients?
Increased Serum Iron
Increased Ferritin (protein that stores iron in the liver)
Decreased TIBC (total iron binding capacity)
Patients with beta thalassemia major need repeated blood transfusions, why?
Due to lack of HbA (worst type of anemia)
What do patients with beta thalassemia major die from?
Most common cause of death is CHF secondary to hemochromatosis
---in a state of iron overload and keep getting blood transfusions so more and more overload of iron --- decreased hepcidin
What are the complications of beta thalassemia major?
1. Hemochromatosis: bronze skin, diabetes, arthritis, restrictive cardiomyopathy, liver cirrhosis, pseudogout
2. Shuts down anterior pituitary: no TSH so thyroid gland atrophies and therefore secondary hypothyroidism ; no LH so testicular atrophy and infertility; no ACTH so secondary adrenal cortical insufficiency so low cortisol
3. Bilirubin gallstones (Cholelithiasis)
4. Encapsulated bacterial infections
5. Aplastic crisis (Parvo B19 - causing reticulocytopenia)
6. Sepsis due to iron loving bacteria: Vibrio Vulnificus and Yersinia Enterolytica (mimics acute appendicitis)
7. Megoblastic anemia due to using up all the folate in the body
What is treatment for beta thalassemia major?
The next anemia that will be discussed is iron deficiency anemia, which is what type of anemia?
Microcytic Hypochromaic Anemia
There are 4 etiologies for iron deficiency anemia each card will go through one. The first etiology is...
1. Nutritional deficiency: very common in children---most of iron intake is from meat as heme iron and grains as stored non heme iron so its okay to give kids meat.
The 2nd etiology for iron deficiency anemia is....
2. Malabsorption: Iron is absorbed in duodenum
--Celiac Sprue (gluten sensitive entropathy)
---Tropical Sprue (bacterial)
---Whipple's (gram positive bacteria common in white men)
3rd etiology for iron deficiency anemia is ...
3. Increased demand
--growing infants and children
4th etiology for iron deficiency anemia is..
4. Chronic blood loss
---Right sided colon cancer (Due to occult blood)
---Uterine fibroids in nulliparous black women who get heavy periods
---Peptic ulcer causes melena
--Gastric cancer or esophagus cancers
Plummer Vision Syndrome is super un common but happens mostly in middle aged women , what is the triad of etiologies?
1. Iron deficiency anemia (fatigue)
2. Glossitis: beefy tongue
3. Esophageal Webbing: dysphagia
How does a patient with iron deficiency anemia present?
--no jaundice due to no elevation in bilirubin
--normal LDH and bilirubin
What is the best investigation for iron deficiency anemia?
Bone marrow biopsy with Prussian Blue staining (Way to invasive to do clinically)
--hypocellular bone marrow because its a production problem not enough iron to make red cells.
What are the lab values for a patient with iron deficiency anemia?
Storage Iron is depleted: so decreased ferritin and increased TIBC
Serum Iron is depleted: low serum iron and low % saturation
What is seen on peripheral blood smear in patients with iron deficiency anemia?
Poikilocytosis (elevated RDW)
Pencil Red Cells
Hypochromic (low MCHC--decreased Hb)
Microcytic (low MCV--small RBC)
Thrombocytosis (idiopathic--elevated platelet count)
Reticulocytopenia (no iron to make reticulocytes)
What are the complications for iron deficiency anemia?
2. Esophageal webs can become squamous carcinoma of the esophagus
3. Pica (eat soil/dirt) due to the chronic iron deficiency
4. Spooning of Fingernails: Koilonychia
Pregnant women need iron supplements as well as what?
Vit C this is for them to be able to absorb iron in the duodenum
What is the normal iron metabolism?
Iron is absorbed in the duodenum. Nonheme iron is carried across the apical and basolateral membranes of enterocytes by transporters
---after reduction by ferric reductase, ferrous iron (Fe2) is transported across the apical membrane
---A second transporter, ferroportin, then moves iron from the cytoplasm to the plasma across the basolateral membrane
--the newly absorbed iron is next oxidized by hephaestin and ceruloplasmin to ferric iron (Fe3), this binds to transferrin.
What is the pathogenesis for iron deficiency anemia?
decreased iron ---- decreased heme ---- decreased hemoglobin --- microcytic anemia
When the body is replete with iron, what happens?
Most iron entering duodenal cells is handed of to ferritin and transfer to plasma transferritin is enhanced when iron is deficient or erythropoiesis is inefficient