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Anemias by Pathoma
Terms in this set (123)
Anemia is characterized by what three findings?
1) Decreased Hemoglobin
2) Decreased RBC Count
3) Decreased Hematocrit
Microcytic Anemias (MCV<80fL)
Anemia of Chronic Disease (ACD)
X-Linked Sideroblastic Anemia
Iron Deficiency Anemia Type
-Microcytic, Hypochromic Anemia
Iron Deficiency Anemia Molecular Cause
-due to decreased levels of Iron
-DOWN Iron --> DOWN Heme --> DOWN Hemoglobin --> MICROCYTIC ANEMIA
Iron Deficiency Anemia Lab Values
-DOWN Ferritin, UP TIBC
-DOWN Serum Iron, DOWN % Saturation
-UP Free Erythrocyte Portoporphyrin (FEP)
Iron Deficiency Anemia Treatment
-Ferrous Sulfate and Treatment of Underlying Cause (GI Problems, Plummer Vinson Syndrome)
Anemia of Chronic Disease (ACD) is associated with...
Chronic Inflammation or Cancer
ACD is most common in...
Chronic Disease results in production of Acute Phase Reactants from the Liver, including...
ACD is mainly characterized by a...
...decrease in available Iron, which leads to a Microcytic Anemia
-sequesters Iron in storage sites by a) limiting iron transfer from macrophages to erythroid precursors and b) suppressing EPO production.
ACD Lab Values
-UP Ferritin (in ACD, you cannot use stored Fe, thus it piles up and upregulates Ferritin transcription), DOWN TIBC
-DOWN Serum Iron, DOWN % Saturation
-UP Free Erythrocyte Portoporphyrin (FEP)
Treatment for ACD
-exogenous EPO (for cancer patients and those with Chronic Kidney Disease)
-or address the underlyling cause!
Sideroblastic Anemia Cause
-DOWN Protoporphyrin--> DOWN Heme --> DOWN Hemoglobin --> MICROCYTIC ANEMIA
When protoporphyrin is deficient, iron...
...remains trapped in mitochondria.
Congenital Sideroblastic Anemia Affected Enzyme
-ALA Synthase issue (the rate limiting enzyme)
Acquired Sideroblastic Anemia
-Alcoholism: mitochondrial poison
-Lead Poisoning: inhibits ALAD and Ferrochelatase
-Vitamin B6 Deficiency: B6 is a required cofactor for ALA Synthase. This deficiency is most commonly seen as a side effect of Isoniazid Treatment for Tuberculosis.
Sideroblastic Anemia Lab Values
-HIGH Ferritin (due to Bone Marrow Macrophages taking up leaked Fe from damaged RBCs)
-HIGH Serum Iron
-High % Saturation
-DECREASED Synthesis of Globin Chains --> DECREASED Hemoglobin --> MICROCYTIC ANEMIA
A Thalassemia Inherited Mutation makes carriers protected against...
Plasmodium falciparum malaria
Alpha-Thalassemia is due to a ___
Gene DELETION! There are 4 alpha alleles on Chromosome 16!
1 Alpha Gene Deletion
2 Alpha Gene Deletion
-Mild Anemia with slightly INCREASED RBC Count
-Cis Deletion (same chromosome)=ASIANS. THIS IS WORSE!
-Trans Deletion (opposite chromosomes)=AFRICANS
3 Alpha Gene Deletion
-Beta Chain Tetramers form (HbH) that damage RBCs
HbH is seen via what lab technique?
4 Alpha Gene Deletion
-Lethal In Utero (Hydrops Fetalis)
-Gamma Chain Tetramers form (HbBarts) that damage RBCs
HbBarts is seen via what lab technique?
Beta-Thalassemia is due to ___
Gene MUTATIONS! There are 2 beta alleles on Chromosome 11!
What two mutations are seen in Beta-Thalassemia?
-Point Mutations in Promoter Region
-Splice Site Mutations
Beta Thalassemia Minor
-mild, usually asymptomatic with increased RBC count
-Beta Normal/Beta +
-microcytic, hypochromic RBCs and target cells on a blood smear.
Beta Thalassemia Minor Lab Values
-Hemoglobin Electrophoresis shows INCREASED HbA2
Beta Thalassemia Major
-most severe form of disease with severe anemia a few months after birth
-Beta Null/Beta Null
-HbF (at birth) is temporarily protective
Beta Thalassemia Major and tetramers?
-Alpha Tetramers will percipitate and damage RBC membranes.
Alpha Tetramer percipitation and RBC damage results in...
1) Ineffective Erythropoiesis
2) Extravascular Hemolysis
Quintessential Phenotypes of Beta Thalassemia Major are a result of
-Major Erythroid Hyperplasia
Beta Thalassemia Major Phenotype
-expansion of hematopoiesis into marrow of skull and facial bones (Crewcut Skull and Chipmunk Face)
-extramedullary hematopoiesis with Hepatosplenomegaly
-risk of aplastic crisis with Parvovirus B19
Beta Thalassemia Major Treatment
-Chronic Transfusions, which lead to a risk for Secondary Hemochromatosis
Beta Thalassemia Major Lab Values
-Hemolytic Electrophoresis shows Little to No HbA, INCREASED HbA2 AND HbF
Beta Thalassemia is prevalent in...
Lead Poisoning is a ___ Anemia that inhibits...
-inhibits Ferrochelatase and ALA Dehydratase.
Macrocytic Anemias (MCV>100fL)
-most commonly due to Folate or Vitamin B12 Deficiency
Both Folate and Vitamin B12 Deficiencies are...
Macrocytic, Megaloblastic Anemias
Megaloblastic Anemia is an anemia (of macrocytic classification) that results from...
...inhibition of DNA synthesis during red blood cell production.
...impaired division and enlargement of RBC precursors
Megaloblastic Anemia is indicated by...
Both Folate and Vitamin B12 are necessary for...
Synthesis of DNA Precursors
Dietary Folate is obtained from...
green vegetables and some fruits
Folate is absorbed in...
Folate Deficiency develops...
within months, because body stores are minimal.
Causes of Folate Deficiency
-poor diet (alcoholics, elderly)
-increased demand (pregnancy, cancer, hemolytic anemia)
-folate antagonists (methotrexate, which inhibits dihydrofolate reductase)
Clinical and Laboratory Findings for Folate Deficiency
-DECREASED Serum Folate
-INCREASED Serum Homocysteine
-NORMAL Methylmalonic Acid
Vitamin B12 is required in order to convert...
Methlymalonic Acid to Succinyl CoA
Dietary Vitamin B12 is complexed to...
...Animal Derived Proteins
Vitamin B12 Absorption Process
1) Salivary Gland Enzymes (Amylase) liberate Vitamin B12, which is then bound by R-Binder (also from the Salivary Gland) and carried through the stomach.
2) Pancreatic Proteases in the Duodenum detach Vitamin B12 from the R-Binder.
3) Vitamin B12 binds Intrinsic Factor (made by Gastric Parietal Cells) in the small bowel; the IF-Vitamin B12 Complex is absorbed in the Ileum.
Clinical and Laboratory Findings for Vitamin B12 Deficiency
-Subacute Combined Degeneration of the Spinal Cord
-DECREASE Serum Vitamin B12
-INCREASED Serum Homocysteine
-INCREASED Methylmalonic Acid
What is the most common cause of Vitamin B12 Deficiency?
-Pernicious Anemia! Autoimmune Destruction of Parietal Cells (in the body of the Stomach) leads to Intrinsic Factor Deficiency.
Other causes of Vitamin B12 Deficiency include...
-Terminal Ileum Damage (Crohn Disease or Fish Tapeworm)
-Dietary Deficiency is rare, except in Vegans!
Vitamin B12 Deficiency develops...
over YEARS, because our Livers have large stores of Vitamin B12
Normocytic Anemias (MCV 80-100fL)
.....INCREASED Peripheral Destruction (RBCs being destroyed outside of the Bone Marrow)
.....UNDERPRODUCTION (Bone Marrow is underproducing RBCs)
What is used to distinguish between the two etiologies of Normocytic Anemia?
-young RBCs that are released from the Bone Marrow
A Normal Reticulocyte Count should be...
The blueish hue of Reticulocyte cytoplasm is due to...
A properly functioning marrow responds to anemia by increasing the Reticulocyte Count to...
>3%, this shows that the Bone Marrow is responding to the anemia by trying to make more RBCs.
Why is the RC falsely elevated with Anemia?
-Because Reticulocyte Count is measured as a PERCENTAGE of the total RBCs. Thus, a decrease in the total RBCs falsely elevates the percentage of Reticulocytes.
Peripheral RBC Destruction is termed...
Hemolytic Anemias (which have INCREASED RC) are divided into two groupings...
In Extravascular Hemolysis, the RBCs are destroyed via...
-the Reticuloendothelial System (macrophages of the Spleen, Liver, and Lymph Nodes)
Macrophage Function in Extravascular Hemolysis
-consume RBCs and break down the Hemoglobin
Protoporphyrin is broken down into...
-unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion into bile.
Clinical and Laboratory Findings of Extravascular Hemolysis
-Anemia with Splenomegaly
-Jaudice, due to Unconjugated Bilirubin
-Increased Risk for Bilirubin Gallstones
-Marrow Hyperplasia with corrected RC >3%
Unconjugated Bilirubin causes Jaundice because...
-it overwhelms the ability of the Liver to conjugate it fast enough, thus it builds up!
In Intravascular Hemolysis, the RBCs are destroyed...
Clinical and Laboratory Findings of Intravascular Hemolysis
-Decreased Serum Haptoglobin (tries to save free Hb from leaving the body)
Normocytic Anemias with Predominant Extravascular Hemolysis (3)
-Sickle Cell Anemia
Hereditary Spherocytosis Mechanism
-Spherocytes are not problematic in and of themselves. However, they are less able to maneuver through Splenic Sinusoids and are thus consumed by Splenic Macrophages, resulting in Anemia!
Hereditary Spherocytosis Clinical and Laboratory Findings
-Spherocytes with loss of Central Pallor
-Splenomegaly (due to Macrophage Hypertrophy)
-Jaundice (with unconjugated bilirubin)
-Increases risk for Aplastic Crisis with Parvovirus B19 Infection of Erythroid Precursors
Hereditary Spherocytosis Diagnosis
-Osmotic Fragility Test (increased fragility in Hypotonic Solution)
Hereditary Spherocytosis Treatment
-Splenectomy: anemia resolves, but the Spherocytes persist and Howell-Jolly Bodies (fragments of nuclear material in RBCs) emerge on blood smear.
Sickle Cell Polymerization is...
What increases Sickling?
5 Complications associated with Vaso-Occlusion
2) Autosplenectomy: causes increased risk of infection with Encapsulated Organisms)
3) Acute Chest Syndrome (most common cause of Death in HbS Adults)
4) Pain Crisis
5) Renal Papillary Necrosis (Hematuria and Proteinuria)
On a Smear of Sickle Cell TRAIT...
NO SICKLING WILL BE SEEN!
Sickle Cell Anemia Laboratory Findings
-Metabisulfite Screen causes cells with any amount of HbS to Sickle
-Hb Electrophoresis confirms the presence and amount of HbS
Sickle Cell Anemia Disease vs Traits Hemoglobin Concentrations
Disease: 90% HbS, 8% HbF, 2% HbA2, no HbA
Trait: 55% HbA, 43% HbS 2% HbA2
Sickle Cell Treatment
Hydroxyurea (which increases levels of HbF) and Hydration
Hemoglobin C Cause
-Autosomal Recessive Mutation in Beta Chain of Hemoglobin. Glutamic Acid replaced by Lysine.
-Mild Anemia due to Extravascular Hemolysis
-Characteristic HbC Crystals are seen in RBCs on Blood Smear
Normocytic Anemias with Predominant Intravascular Hemolysis
-Paroxysmal Nocturnal Hemoglobinuria (PNH)
-Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
-Immune Hemolytic Anemia (IHA)
-Microangiopathic Hemolytic Anemia
Paroxysmal Nocturnal Hemoglobinuria (PNH)
-acquired defect in Myeloid Stem Cells, resulting in absent GPI
-renders cells susceptible to destruction by complement.
Blood cells coexist with...
What two substances on the surface of RBCs inactivate Complement?
-DAF (Decay Accelerating Factor) and MIRL.
DAF is secured to the cell membrane by...
-GPI (an anchoring glycolipid)
Absence of GPI leads to absence of DAF, which...
...renders cells susceptible to complement-mediated damage.
Paroxysmal Nocturnal Hemoglobinuria (PNH) Diagnosis Test
Paroxysmal Nocturnal Hemoglobinuria (PNH) Complications
-Iron Deficiency Anemia
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Genetics and Overall Problem
-X-Linked Recessive Disorder resulting in reduced half life of G6PD.
-renders cells susceptible to oxidative stress
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Pathway
-Glutathione (an antioxidant) neutralizes H2O2, but becomes oxidized in the process. NADPH, a byproduct of G6PD is needed to reverse this reaction.
-DOWN G6PD --> DOWN NADPH --> DOWN Reduced Glutathione--> INCREASED Oxidative Injury by H2O2 --> Intravascular Hemolysis
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Causes
-Fava Beans (Mediterranean People!)
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency has a protective role against...
In Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Oxidative Stress percipitates Hb as...
...Heinz Bodies, which are removed by Splenic Macrophages, resulting in Bite Cells. This leads to predominantly Intravascular Hemolysis.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Mneumonic
"Stress makes me eat bites of fava beans with Heinz Ketchup"
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Other Presentations
Immune Hemolytic Anemia (IHA)
-antibody-mediated (IgG or IgM) destruction of RBCs
IgG-Mediated Disease + Mnemonic + RBC Type + Mechanism
-usually involves extravascular hemolysis
-IgG binds RBCs in the relatively warm central body ("WARM weather is GREAT")
-the membrane of antibody-coated RBC is consumed by Splenic Macrophages
Drugs commonly associated with IgG-Mediated Disease are...
Two Possible Mechanisms for Drug Cause of IgG-Mediated Disease
1) Drugs many attach to the RBC Membrane (like Penicillin) with subsequent binding of antibody to drug-membrane complex
2) Drugs may induce production of autoantibodies (alpha-methyldopa) that bind self antigens on RBCs
Treatment of IgG-Mediated Disease
-cessation of the offending drug
-IVIF (buys you time)
IgM-Mediated Disease + Mneumonic + RBC Type + Mechanism
-usually involves intravascular hemolysis
-IgM binds RBCs and fixes complement in the relatively cold temperature of extremities ("COLD weather is MMMiserable")
-IgM (Cold) Agglutinin is caused my Mycoplasma pneumonia infections and Infectious Mononucleosis
IHAs are usually Coombs...
Direct Coombs Test
-Anti-IgG Antibodies (Coombs Reagent) added to patient's blood to determine if PATIENT's RBCs are already coated with IgG
Indirect Coombs Test
-normal, test RBCs added to patient's SERUM to determine PATIENT's SERUM has anti-RBC IgGs. Then, Coombs Reagent (Anti IgG Antibody) is added.
Microangiopathic Hemolytic Anemia
-intravascular hemolysis that results from vascular pathology
-RBCs are destroyed as they pass through circulation
Microangiopathic Hemolytic Anemia Smear Findings
-SHISTOCYTES (Helmet Cells) are seen on blood smear due to mechanical destruction of RBCs
Microangiopathic Hemolytic Anemia Causes
-Prosthetic Heart Valves
Anemia due to Underproduction
Basic Principles of Anemia due to Underproduction
-decreased production of RBCs by Bone Marrow
-characterized by low corrected Reticulocyte Count
Etiologies of Anemia due to Underproduction
1) causes of Microcytic and Macrocytic Anemia
2) Renal Failure (decreased production of EPO by Peritubular Interstitial Cells)
3) Damage to Bone Marrow Precursor Cells
-infects progenitor RBCs
-temporarily halts Erythropoiesis
-leads to significant anemia in the setting of preexisting marrow stress
-Supportive Treatment only...
-damage to Hematopoietic Stem Cells
-results in Pancytopenia with low Reticulocyte Count
Etiologies of Aplastic Anemia
-drugs or chemicals
In Aplastic Anemia, BM Biopsy reveals
-empty, fatty marrow
Treatment of Aplastic Anemia
-cessation of any causative drugs
-Bone Marrow Transplant (as a last resort)
-pathologic process (like metastatic cancer) that replaces Bone Marrow.
-Hematopoiesis is impaired, resulting in Pancytopenia.
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