[4] Anemia Flashcards
Definition of Anemia in Males and Females
Hb < 13.5 g/dL in Males
Hb < 12.g g/dL in Females
Based on MCV, anemia is classified as?
Microcytic: MCV < 80
Normocytic: MCV = 80 - 100
Macrocytic: MCV > 100
What is the progenitor RBC?
Erythroblast
Microcytic anemias are due to what defect?
Decreased production of Hb
Heme is composed of?
Iron and Protoporphyrin
Sideroblastic Anemia is due to?
Defective protoporphyrin synthesis
How do Thalassemias cause Microcytic Anemia?
Decreased production of globin chains
Most common type of anemia
Iron Deficiency Anemia
Absorption of heme occurs in what part of the GIT?
Duodenum
What is responsible for the uptake of iron in the gut?
Enterocytes
Iron is bound to this molecule in the blood
Transferrin
Storage sites for iron in the body
Liver and Bone Marrow
What does TIBC measure?
Amount of Transferrin in the blood
What does Serum Ferritin measure?
How much iron is in the storage sites
These parasites are common causes of iron deficiency
Necator and Ancylostoma (Hookworms)
How goes gastrectomy cause IDA?
Decreased acid would cause less iron to be in a reduced state (Fe 2+), which is better absorbed compared to Fe3+
RBCs in early stage Iron Deficiency Anemia present as?
Normocytic Anemia
Function: Hepcidin
Sequesters iron in storage sites
How does chronic disease cause iron deficiency anemia?
Release of acute phase reactants cause:
Hepcidin: Iron sequestration
Decrease of EPO production
What enzyme is the rate-limiting step for the production of Protoporphyrin?
Aminolavalunic Acid Synthase (ALAS)
What is the Co-Factor for the rate-limiting step for the production of Protoporphyrin?
Vitamin B6
Classic presentation of a RBC in Sideroblastic Anemia
Ring Sideroblast (Ring of Iron that is trapped inside the mitochondria)
Most common form of congenital Sideroblastic anemia is caused by?
Loss of ALAS
Common causes of Acquired Sideroblastic Anemia
Alcoholism: Mitochondrial poison damages the production of protoporphyrin
Lead Poisoning: Denatures ALAD and Ferrochelatase
Vitamin B6 Deficiency: Co-factor for the first step of Protoporphyrin production
Laboratory Findings in Patients with Sideroblastic Anemia
Ferritin: +
TIBC: -
Serum Iron: +
% Saturation Iron: +
Laboratory Findings in Patients with Iron Deficiency Anemia
Ferritin: -
TIBC: +
Serum Iron: -
% Saturation Iron: -
How do Thalassemias cause anemia?
Decreased synthesis of globin chains
Usual cause of alpha-thalassemias
Gene Deletion
Normally there are 4 Alpha Alleles are present on Chromosome 16
In an alpha-thalassemia, is a cis deletion or trans deletion worse?
Cis deletion (Same gene knockout)
Associated with increased risk of severe thalassemia in offspring
Usually seen in Asians
What is the pathophysiology that occurs in a 3 gene deletion alpha-thalassemia?
B chains may form tetramers that cause RBC damage
Patients present with severe anemia
What is the pathophysiology that occurs in a 4 gene deletion alpha-thalassemia?
y chains form tetramers (Hb Barts) that damage RBCs
Fatal in utero (Hydrops fetalis)
Beta-Thalassemia is caused by?
Gene Mutation (Not deletions like Alpha-thalassemias)
Two B genes are present on Chromosome 11, mutations result in absent (B0) or diminished (B+) production of B-globin chains
What is the mildest form of Beta-Thalassemia?
B/B+ (Beta-Thalassemia Minor)
Usually asymptomatic with increased RBC count
What is the most severe form of Beta-Thalassemia?
When does this disease present in the patient? Why?
B0/B0 (Beta-Thalassemia Major)
Presents with severe anemia a few months after birth because HbF (A2Y2) at birth is temporarily protective
Treatment for patients with Beta-Thalassemia?
What is a complication of this treatment?
Chronic Transfusion
May cause secondary hemochromatosis (Remember that the body does not really have a way to remove iron)
Presentation of Beta-Thalassemic RBCs on Blood Smear
Microcytic, hypochromic target cells with nucleated red blood cells
Electrophoresis presentation of Beta-Thalassemia Major
HbA: - or 0
HbA2: +
HbF: +
Most common cause of Macrocytic Anemia
Folate or Vitamin B12 Deficiency (Megaloblastic Anemia)
How does folate or vitamin B12 deficiency cause anemia?
Impairs synthesis of DNA precursors
What drug commonly causes macrocytic anemia?
5-FU
Where is folate obtained from and where is it absorbed in the GIT?
Folate is obtained from green, leafy vegetables
Jejunum
Blood smear finding of Macrocytic Anemia
Macrocytic RBCs Hypersegmented Neutrophils (>5 lobes)
How does methylmalonic acid help differentiate a folate and vitamin B12 deficiency?
Normal serum levels of methylmalonic acid points to a folate deficiency as Vitamin B12 is necessary for its conversion to succinyl CoA
In what part of the GIT is Vitamin B12 absorbed?
Ileum
Why is Vitamin B12 deficiency less common than folate deficiency?
There is a large hepatic store of Vitamin B12
Most common cause of Vitamin B12 deficiency
Pernicious Anemia
Autoimmune destruction of parietal cells leading to IF deficiency: Vitamin B12 binds to IF to be absorbed in the ileum
How does pancreatic insufficiency cause B12 deficiency?
Lack of proteases to cleave the B12-R Factor unit, which prevents IF from binding to B12 for absorption
What are reticulocytes?
Young RBCs released from bone marrow
RBC Lifespan
120 Days
How do you correct reticulocyte count?
Reticulocyte x Hct/45
Define: Hereditary Spherocytosis
Inherited defect of RBC cytoskeleton membrane tethering proteins
Ankyrin, spectrin and band 3:1
How does having a spherocyte shape of RBC cause anemia?
Unable to effectively pass through splenic sinusoids causing excessive destruction
Diagnostic test for Hereditary Spherocytosis
Osmotic Fragility Test
Increased fragility in hypotonic solution
Treatment for Hereditary Spherocytosis
Splenectomy
What is a Howell-Jolly Body?
Histopathologic finding of remnant DNA in Erythrocytes usually seen in patients with severe splenic dysfunction
What is the cause of Sickle Cell Anemia?
AR Mutation in B Chain of Hemoglobin
Glutamic Acid replaced by Valine
What is the predominant Hb of Sickle Cell Anemia? What is the problem with this type of Hb?
HbS
These Hb polymerize when under oxidative stress causing the classic sickle pattern
Treatment for Sickle Cell Anemia
Hydroxyurea
Causes increase of HbF, which is protective against sickling
Most common cause of death for children with sickle cell anemia
Infection by encapsulated organisms (H. influenza, Strep pneumo)
Results from autophagy of the spleen
Most common cause of death for adults with sickle cell anemia
Acute chest syndrome
Caused by vasoocclusion of pulmonary vasculature, usually preceded by an infection
Cause of Hemoglobin C
AR defect of Hemoglobin B chain
Glutamic Acid is replaced by Ly-C-ine
Pathophysiology of Paroxysmal Nocturnal Hemoglobinuria
Acquired defect in myeloid stem cells resulting in absent GPI
Renders cells susceptible to complement
(occurs at night due to mild respiratory acidosis that occurs during sleep)
Screening Test for Paroxysmal Nocturnal Hemoglobinuria
Sucrose Test
Confirmatory Test for Paroxysmal Nocturnal Hemoglobinuria
Acidified Serum Test
Flow Cytometry to detect lack of CD55 (DAF)
In patients with G6PD Deficiency oxidative stress causes Hb to precipitate as?
Heinz Bodies
What are some common causes of oxidative stress in patients with G6PD?
Infections
Drugs (Primaquine, sulfa drugs, dapsone)
Fava beans
Presentation of patients with G6PD
Hemoglobinuria and Back Pain
Pathophysiology of Autoimmune Hemolytic Anemia
IgG or IgM mediated destruction of RBC
Treatment of Autoimmune Hemolytic Anemia
Cessation of offending drug
Steroids
IVIG
Splenectomy
Test used to diagnose Immune Hemolytic Anemia
Coombs Test
Which of the Coombs Tests are more important in the diagnosis of Autoimmune Hemolytic Anemia?
Direct Coombs: Anti-IgG is added to patients RBCs. If they are already coated with IgG, then they will agglutinate.
[Indirect Coombs: Tests whether the patients serum has the antibody]
Hallmark of Microangiopathic Hemolytic Anemia
Schistoscytes
Define: Myelophthisic Process
Pathologic process that replaces bone marrow resulting in pancytopenia
