Heme/Onc - Week 2 Review - Part 3 - Anemia

Question 1

Classifications of Mean Corpuscular Volume (MCV) - 3

Answer 1

Microcytic < 80
Normocytic - 80 to 100
Macrocytic > 100

Question 2

Microcytic Anemia - 5 Types

Answer 2

1) Iron Deficiency Anemia
2) Anemia of Chronic Disease
3) Sideroblastic Anemia
4) Thalasemia
5) Lead Poisoning

Question 3

Macrocytic Anemia - 2 Subdivisions - 5 Anemias

Answer 3

Megaloblastic Macrocytic - B12 and Folate

Non-Megaloblastic Macrocytic - Liver Disease + EtOH + Drugs (5-FU)

Question 4

Normocytic Anemia with Extravascular Hemolysis (5)

Answer 4

1) Heriditary Spherocytosis
2) Sickle Cell
3) Hemoglobin C
4) Beta Thalessemia (Microcytic)
5) Immune Hemolytic Anemia - IgG Mediated

Question 5

Normocytic Anemia with Intravascular Hemolysis (5)

Answer 5

1) Paroysmal Nocturnal Hemoglobinuria
2) G6PD Deficiency
3) Immune Hemolytic Anemia - IgM Mediated
4) Microangiopathic Anemia
5) Malaria

Question 6

Normocytic Anemia with Underproduction (2)

Answer 6

1) Parvovirus B19

2) Aplastic Anemia

Question 7

Classic S/Sx of Anemia (5)

Answer 7

1) Weakness
2) Fatigue
3) Pale Conjuntiva/Skin
4) Lightheaded/Headache (CNS Hypoxia)
5) Anigina (with preexisting CAD)

Question 8

Microcytic Anemia - 4 Major Types to Review + Associated Defect

Answer 8

1) Iron Deficiency - Lack of Heme
2) Anemia of Chronic Disease - Lack of Heme
3) Sideroblastic Anemia - Lack of Protoprphorin
4) Thalesemia - Lack of Globulin Chain

Question 9

Pathway of Iron Absorption

Answer 9

1) Absorbed in the duodenum via DMT1 transporters
2) Transported into the blood via ferroportin
3) Transferrin binds free Iron
4) Ferritin stores Iron

Question 10

Major Laboratory Measures of Blood (4)

Answer 10

1) Serum Iron
2) Serum Ferratin (Stored Iron)
3) TIBC = Total Iron Binding Capacity - Amount of Transferritin
4) % Saturation = Amount of Transferrin bound by iron - normally 33%

Question 11

Iron Lab Values in Iron Deficiency Anemia vs. Anemia of Chronic Disease

Answer 11

Iron Deficiency

1) Reduced Serum Iron + Saturation
2) Reduced Ferritin (Nothing to Store)
3) Elevated Transferritin (body looking or more iron

Chronic DIsease

1) Reduced Serum Iron
2) Increased Ferritin (all stored)
3) Decreased Transferritin (TIBC)

Question 12

Major Causes of Iron Deficiency (7)

Answer 12

Absorption Issue

1) Breast Milk (infants)
2) Children (poor diet)
3) Malabsorption (Celiac)
4) Gastrectomy (Loss of stomach = less acid = less Fe2+ Iron = Less Absorbed)

Leech Issue

5) Peptic Ulcer
6) Hookworm
7) Colon Polyp/Carcinoma (Bleeds)

Question 13

Change in Non-Iron Labs in Iron Deficiency Anemia (3)

Answer 13

1) Increased Free Erythrocyte Protoporphyrin (Still made but with not heme to bind)
2) Increased RDW (Cell Sizes Vary)
3) Low Hb/Hct

Question 14

Additional Key Iron Deficiency S/Sx (2)

Answer 14

1) Pica - Eat dirt due to psychological drive to get iron

2) Koilonychias (Spoon Shaped Nails)

Question 15

Plummer Vinson Syndrome - Triad

Answer 15

1) Iron Deficiency Anemia
2) Glossitis
3) Esophageal Webs

Typically presents as dysphagia with anemia

Question 16

Anemia of Chronic Disease - Pathophisiology

Answer 16

Chronic inflammation activates immune system - Immune system responds by increasing hepcidin

Hepcidin hides Iron (with Ferritin) - Done to prevent bacteria from using the Iron

Question 17

Sideroblastic Anemia - Mechanism of Anemia + Causes (4)

Answer 17

Mechanism - Decreased Protoporphyrin production - can’t make heme - Iron still goes into the mitochondria and gets trapped (Sideroblasts formed) - Free radial damage from the iron causes cell rupture

Causes

1) Congenital - ALAS Deficiency
2) Alcoholism (MItochondrial Poisoning)
3) Lead Poisoning (Inhibits ALAD + Ferrochetalase)
4) B6 Deficiency (ALAS Co-Factor - Common with Isoniazad Therapy for TB)

Question 18

Protoporphyrin Synthesis - Key Steps (3)

Answer 18

1) Succinyl CoA - Converted to Aminoleuvinic Acid (ALA) via ALA Synthase (ALAS) + Vitamin B6 (Co-Factor)
2) ALA Converted to Porphobiligin via ALAD
3) Eventually transitioned to protophorin - made to heme via Iron addition (ferrochetalase) - Step Occurs in Mitochondria

Question 19

Lab Findings in Sideroblastic Anemia (4)

Answer 19

Lab Findings - All Due to Iron Overloaded State (Ruptures Membrane)

1) Increased Serum Fe (Cell Lysis)
2) Increased % Saturation + Ferritin (Stored cause you can’t use)
3) Low TIBC (Low Transferritin) - Lots circulating, don’t want to promote more

Histology - SIderoblastic Microcytic RBCs (Ringing with Blue Iron)

Question 20

Alpha Thalassemia - Mutation and Gene Location

Answer 20

Mutation of Chromosome 16 - 4 Possible Genes

Question 21

Alpha Thalassemia - Results of # of Mutations

Answer 21

1 Deletion - Asymptomatic
2 Deletions - Mild Anemia - Cis (Asian) is worse - both on same chromosome
3 Deletions - Severe Anemia - Beta Chain Tetromeres (HbH) Damage RBCs
4 Deletions - Fetal Death (Hydrops Fetalisis) - Gamma Chain Tetromeres (HbBarts)

Question 22

Beta Thalassemia - Mutation + Gene Location

Answer 22

Point Mutation - Can be Beta+ or Beta-Null

Chromosome 11

Question 23

Beta Thalassemia Minor - Genetics + Presentation

Answer 23

Genetics - B/B+ - Most Mild Form
Asymptomatic with increased RBC Count - Microcytic Hypochromic Cells

Target Cells on Smear

Question 24

Beta Thalassemia Major - Genetics + Sub-Populations + Labs (3)

Answer 24

Major = Beta-Null/Beta+

African Populations - Alpha and Beta Thalassemia
Mediterranean = Beta Thalassemia

Labs for Beta Major
Microcytic Hypochromic RBCs
Nucleated RBCs (Splenic Production)
Target Cells

Question 25

Beta Thalassemia Major - Presentation + Findings (5)

Answer 25

Presentation - Presents after HbF Drops Findings 1) Alpha Tetramers Aggregate - Extravascular Hemolysis 2) Massive Erythoid Hyperplasia - Skull hematopoeisis = Crew-Cut Skull 3) Facial Bone Hematopoeisis - Chipmunk Facies 4) Hepatosplenomegaly 5) High risk of Aplastic Crisis with Parvovirus B19 Infection

Question 26

Major Causes of Macrocytic Anemia (2)

Answer 26

Folate and B12 Deficiency (Megoblastic)

Question 27

Folate/B12 Pathway

Answer 27

Folate Absorbed as Tetra-Dihydrofolate - THF-Methylated for circulation - B12 removes the Methyl allowing for DNA Synthesis - B12 Produces Methionine from Homocystine in the Processs

Question 28

Impacts of Impaired DNA Synthesis (3)

Answer 28

1) Impaired RBC Synthesis - Macrocytic Anemia 2) Impaired Division of Granulycytic Precursors - Hyper-segmented Neutrophils (>5 Lobes) 3) Gut Enlargement of intestinal epithelium

Question 29

Folate Deficiency Causes (3)

Answer 29

1) Poor Diet - EtOH + Elderly 2) Increased Demand - Pregnancy - No Folate leads to congenital defects 3) Drugs (Methotrexate)

Question 30

Folate Deficiency Alternative Name

Answer 30

1) Giardiasis

Question 31

Folate Deficiency Findings (5)

Answer 31

1) Macrocytic RBCs 2) Hyper-Segmented Neutrophils 3) Low Serum Folate 4) Elevated Serum Homocystine (Not used by B12) 5) Glossitis

Question 32

Vitamin B12 Absorption Pathway - 5 Steps

Answer 32

1) Salivary Amylase Liberated B12 2) R-Binder holds B12 through the stomach 3) Pancreatic Proteases free B12 4) B12 Binds Gastric Parietal Cell Produced Intrinsic Factor 5) B12-IF Absorbed in the ileum

Question 33

Causes of B12 Deficiency (4)

Answer 33

1) Precocious Anemia = #1 Cause - Autoimmune Destruction of Parietal Cells (3 P's - Proton Pump + Pink + Precocious Anemia 2) Pancreatic Insufficiency (No Removal of R-Binder Protein) 3) Diet (Vegan) - Rare 4) Damage to the Ileum (Crohn's Disease)

Question 34

B12 Deficiency - Clinical Findings (3)

Answer 34

1) Macrocytic Anemia with Hyper-segmented Neutrophils 2) Glossitis 3) Sub-Acute Combined Degeneration of SC - Methylmalonic acid Build but destroys DCMLT + CST)

Question 35

B12 Deficiency - Keys Labs (4) + Key Test

Answer 35

1) Smear - Macrocytic Anemia with Hyper-segmented Neutrophils 2) Low Serum B12 3) High Homocystine (no Methionine ProductioN) 4) High Serum Methylmalonic Acid (No Succinyl CoA Production) Schilling Test - Give Pt. Labeled B12 - Check if it makes it to the urine - If not give with IF and see if it makes it Give IF - See B12 in Urine - Means Precocious Anemia (with lack of IF)

Question 36

Reticulocyte Count - Definition + Calculation + Impact of Corrected Count

Answer 36

Reticulocyte = Pre-mature RBC (24 hours) - Bluish cytoplasm from RNA - Normally 1-2% of RBCs Calculation of Corrected Count = (Reticulocyte Count * Hct) / 45 Normal Hct = 45 Corrected > 3% = Bone Marrow responding = Hemoylsis Corrected < 3% = Bone Marrow not responding = Underproduction

Question 37

Extravascular Hemolysis - Location + Impacts + Major Findings (4) + Causes (4)

Answer 37

Macrophages destroy cells in Spleen/Liver/Lymph Nodes Globin Broken down in AA and Heme in Iron (Recycled) And Protoporphoryin (bilirubin) Findings 1) Anemia with splenomegaly 2) Jaundice (Elevated Bilirubin 3) Gallstones (Supersaturated with Bilirubin) 4) Marrow Hyperplasia Causes 1) Hereditary Shpherocytosis 2) Sickle Cell 3) Hemoglobin C

Question 38

Intravascular Hemolysis - Location + Impacts + Major Findings (3) + Causes (5)

Answer 38

Occurs in the vessel - Initial change results in low haptaglobin (haptaglobin binds up all the free hemoglobin) Findings 1) Hemoglobinemia (Lots of Hemoglobin in the blood 2) Hemoglobinuria (in the urine) 3) Hemosiderinuria (RT Cells pick up Hb and hold for a few days before they die Causes 1) PNH 2) G6PD 3) Immune Mediated 4) Microangiopathic Anemia 5) Malaria

Question 39

Hereditary Spherocytosis - Type of Anemia + Pathophysiology

Answer 39

Normocytic Anemia with Extravascular Hemolysis Defect in Ankyrin/Spectrin/ or Band 3:1 - Leads to issues with cytoskeletal teething of RBCs ---- Creates membrane blebs which are removed by the spleen - Cells become round vs. dumbbell - Can't pass splenic capillaries causing lysis

Question 40

Hereditary Spherocytosis - Clinical Findings (3) + Labs (3)

Answer 40

Clinical 1) Hepatosplenomegaly 2) Jaundice 3) Increased risk for aplastic crisis with Parvovirus B19 Labs 1) Spherocytes on smear 2) Increased RDW - Cell Sizes Vary 3) Increased Mean Corpuscular Hb Concentration (MCHC) = More Red

Question 41

Hereditary Spherocytosis - Diagnosis + Treatment (2)

Answer 41

Dx - Fragility Test - Hypotonic solution causes spherocyte rupture but not normal RBCs Treatment - Spleenectomy - Howell-Jolly Bodies Reamin (RBCs DNA Left-Overs normally clearned by the spleen

Question 42

Sickle Cell Anemia - Type of Anemia + Genetics

Answer 42

Normocytic Anemia with Extravascular Hemolysis Genetics - Autosomal Recessive Single AA Substitutions in Hb on Chromosome 11 (Valine replaces a Glutamic Acid) - Beta Globin Gene

Question 43

Sickle Cell Anemia - Pathophysiology + Triggers (4)

Answer 43

HbS - Occurs with 2 Defective Genes --> Polymerizes under oxidative stress + Aggregates into needle stick struckes - continuously sickles + unsickles Triggers 1) Cold 2) Hypoxemia 3) Acidosis 4) Dehydration

Question 44

Sickle Cell Anemia - Clinical Findings (5) + Causes

Answer 44

AREAS A - Autosplenectomy (Increased Infections) + Target Cells + Howell Jowell Bodies R - Renal Papillary Necrosis - From Howell Jowell Bodies E - Encapsulated Organism Infection (Strep. Pneumoniae + Haemophilus Influenza) A - Asplenic Anemia Risk (Parvovirus B19) S - Salmonella Osteomyletis

Question 45

Sickle Cell Anemia - Lab Findings (4)

Answer 45

1) Target Cells - Asplenia + Blebs 2) Skull = Crew-Cut + Chipmunk Face 3) Metabisulfite Screen - Any amount of HbS will sick - Shows Triat and Disease 4) Hb Electrophoresis shows if it is trait of disease

Question 46

Hemoglobin C - Type of Anemia + Genetics

Answer 46

Normocytic Anemia with Extravascular Hemolysis ``` Genetics - Autosomal Recessive Beta Globin (Chromosome 11) AA Mutation ``` Glutamic Acid - Lysine (vs. Valine in HbS)

Question 47

Hemoglobin C - Lab Findings (3)

Answer 47

1) Normocytic Anemia with Extravascular Hemolysis 2) Target Cells 3) HbC Crystals on Smear - Little Rectangles

Question 48

Paroxysmal Nocturnal Hemoglobuinuria (PNH) - Type of Anemia + Pathophysiology

Answer 48

Normocytic Anemia with Intravascular Hemoylysis Acquired defect in the myeloid stem cell = loss of GPI (which holds DAF-CD55) on the RBC - No DAF means compliment can attack and lyse RBCs

Question 49

PNH Markers + Gene

Answer 49

Markers - Loss of CD55 and CD59 Genetics - PIG-A Gene (GPI Production

Question 50

PHN Clinical Features (4)

Answer 50

1) Night Time Hemolysis (Acidosis) 2) Morning Hemoglobinuria (Red Urine) 3) Sucruse Screening Test 4) Complications = Iron Deficiency Anemia + Risk of AML (Myeloid keeps mutating)

Question 51

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) - Type of Anemia + Pathophysiology

Answer 51

Normocytic Anemia with Intravascular Hemoylysis Loss of GP6D = Loss of ability to produce NADPH No NADPH = Can't recycle glutathione No Glutathione = High susceptibility to oxidative stress

Question 52

G6PD - Genetics + Variants (2) + Stress Triggers (4)

Answer 52

Genetics - X-Linked Recessive Variants African = Mild Mediterranean - Severe Triggers 1) Fava Beans 2) Acidosis (DKA) 3) Primaquin 4) Sulfonamides

Question 53

G6PD - Lab Findings (3)

Answer 53

1) Normocytic Anemia with Intravascular Hemoylysis 2) Heinz Bodies (Hb accumulations in the cells) 3) Bite Cells - Macrophages take bites out to try and remove Heinz Bodies

Question 54

Immune Hemolytic Anemia - Type of Anemia + Types (2)

Answer 54

Normocytic Anemia with Intravascular or Extravascular Hemoylysis IgG - Macrophage Induced - Extravascular - Warm Agglutinate IgM - Compliment Induced - Intravascular - Cold Agglutinate

Question 55

IgG Mediated Hemolytic Anemia - Type of Anemia + Key Points (2)

Answer 55

Warm Agglutinate + Extravascular Hemolysis Consumption via splenic macrophages creates spherocytes

Question 56

IgG Mediated Hemolytic Anemia - Causes (4) + Treatment (3)

Answer 56

Causes 1) SLE 2) CLL 3-4) Drugs (Methyldopa + Cephalosporin) Treatment 1) Cessation of Drug 2) IVIgG - Throw dog a bone and keep macrophages busy 3) Spleenectomy

Question 57

IgM Mediated Hemolytic Anemia - Type of Anemia + Key Point + Causes (2)

Answer 57

Cold Agglutinate - Intravascular Hemolysis Fixes Compliment Causes - Mycoplasma Pneumonia + EBV

Question 58

Microangiopathic Hemolytic Anemia - Type + Pathophysiology + Causes (4)

Answer 58

Normocytic Anemia with Intravascular Hemolysis RBCs are sheered by the microthrombi as they pass in circulation - results in schistocyte (Helmet Cells) Causes - Micro-Thormbi Disease 1) TTP 2) HUS 3) DIC 4) HELLP

Question 59

Normocytic Anemia Due to Underproduction - Key Finding + Causes (4)

Answer 59

Reticulocyte Count - Low - Not Corrected for Anemia 1) Parvovirus B19 2) Aplastic Anemia 3) Microcytic Anemia (falls in this category) 4) Macrocytic Anemia (falls in this category)

Question 60

Aplastic Anemia - Mechanism + Findings (4)

Answer 60

Damage to HSCs - Triggers Pancytopenia Pancytopenia 1) Anemia 2) Thrombocytopenia (Bleeding) 3) Leukopenia (Infection) 4) Bone Biopsy - Empty Marrow + <10% Cellularity

Question 61

Aplastic Anemia - Causes (4) + Treatment (2)

Answer 61

Causes 1) Viral Infection (Parvovirus B19) 2) Drugs 3) Chemicals 4) Autoimmune - T-Cell Based Treatment - Transfusion + Marrow Stimulation (GM-CSF)