Medicine Marrow Pg 81-90 (Hematology)
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Questions and Answers

What is the most sensitive and specific test for hemolysis?

  • LDH
  • S. haptoglobin (correct)
  • Reticulocyte production index (RPI)
  • S. bilirubin

    • Intravascular hemolysis is primarily located in the blood vessels.

    True

    Name one common cause of acute intravascular hemolysis.

    Mismatched blood transfusion

    During intravascular hemolysis, the urine may show signs of ______.

    <p>hemoglobinuria</p> Signup and view all the answers

    Match the following terms related to hemolysis with their definitions:

    <p>PNH = A genetic condition affecting red blood cell stability MAHA = A type of hemolytic anemia due to blood vessel damage G6PD deficiency = An enzyme deficiency that can lead to hemolysis AIHA = An autoimmune condition resulting in red blood cell destruction</p> Signup and view all the answers

    What is the primary reason for Vitamin B12 absorption issues in individuals?

    <p>Autoimmune disorders</p> Signup and view all the answers

    Intrinsic Factor (IF) is secreted by goblet cells in the stomach.

    <p>False</p> Signup and view all the answers

    What complex forms when Vitamin B12 binds with R-factor in the stomach?

    <p>R-factor/Vitamin B12 complex</p> Signup and view all the answers

    The Vitamin B12-IF complex binds with __________ receptors in the ileum.

    <p>CUBAM</p> Signup and view all the answers

    Match the following Vitamin B12 forms with their characteristics:

    <p>Adenosylcobalamine = Form of Vitamin B12 used in energy metabolism Methylcobalamine = Form of Vitamin B12 important for neuroprotection Holotranscobalamin = Active transport form of Vitamin B12 in circulation Cobalamin = Generic term for Vitamin B12 compounds</p> Signup and view all the answers

    What is the most important cause of Vitamin B12 deficiency?

    <p>Pernicious anemia</p> Signup and view all the answers

    Vitamin B12 is absorbed only in the stomach.

    <p>False</p> Signup and view all the answers

    What are the two key processes in which Vitamin B12 acts as a co-factor?

    <p>Homocysteine to methionine and methylmalonyl CoA to Succinyl CoA.</p> Signup and view all the answers

    The infection caused by Diphyllobothrium latum is associated with Vitamin B __________ deficiency.

    <p>12</p> Signup and view all the answers

    Match the following types of Transcobalamin with their descriptions:

    <p>TC-1 = Produced by granulocytes, increased in myeloproliferative neoplasms TC-2 = Produced in all tissues, especially the liver, important for transport TC-3 = Has some role in the transport of Vitamin B12</p> Signup and view all the answers

    Where in the body is folic acid primarily absorbed?

    <p>Proximal small intestine</p> Signup and view all the answers

    Vitamin B12 deficiency leads to an accumulation of 5-methyl THFA levels.

    <p>True</p> Signup and view all the answers

    Name one major cause of folate deficiency.

    <p>Decreased intake</p> Signup and view all the answers

    The primary form of folate found in food is __________.

    <p>Monoglutamate</p> Signup and view all the answers

    Match the following causes of folate deficiency with their descriptions:

    <p>Nutritional = Decreased intake Celiac disease = Decreased absorption Pregnancy = Increased demand Methotrexate = Drug interference</p> Signup and view all the answers

    Which of the following antibodies are sensitive and specific in the pathogenesis of pernicious anemia?

    <p>Anti-intrinsic factor antibody</p> Signup and view all the answers

    Pernicious anemia is associated with autoimmune conditions like Addison's disease and Type 1 Diabetes Mellitus.

    <p>True</p> Signup and view all the answers

    What are the characteristic clinical features of pernicious anemia?

    <p>Pallor with yellowish tinge, angular cheilitis, atrophic glossitis, and hyperpigmentation.</p> Signup and view all the answers

    Pernicious anemia is often seen in _____ aged women.

    <p>middle-aged to elderly</p> Signup and view all the answers

    Match the findings from bone marrow smear to their descriptions in pernicious anemia:

    <p>Dyserythropoiesis = Abnormal erythroid cell development Erythroid hyperplasia = Increased erythroid precursor cells ↓ myeloid: erythroid ratio = Lower myeloid cells compared to erythroid cells Megaloblasts = Large precursor red blood cells</p> Signup and view all the answers

    At what serum vitamin B12 level is a deficiency diagnosed?

    <p>Below 200 pg</p> Signup and view all the answers

    Methylmalonyl CoA levels are decreased in vitamin B12 deficiency.

    <p>False</p> Signup and view all the answers

    What characterizes Hypersegmented Neutrophils in a peripheral blood smear?

    <p>More than 5 lobes</p> Signup and view all the answers

    The presence of __________ in urine can indicate elevated Methylmalonyl CoA levels.

    <p>Methylmalonic acid</p> Signup and view all the answers

    Match the following features of a peripheral blood smear with their descriptions:

    <p>Megaloblasts = Indicate vitamin B deficiency with abnormal shape &amp; size Hypersegmented Neutrophils = Neutrophils with more than 5 lobes Pseudo-Pelger-Huet cells = Abnormal neutrophils typically having 2-3 lobes Cabot rings = Cylindrical structures often seen in megaloblastic anemia</p> Signup and view all the answers

    Which of the following conditions can lead to megaloblastic anemia?

    <p>Vitamin B12 deficiency</p> Signup and view all the answers

    Thiamine deficiency is a cause of megaloblastic anemia.

    <p>False</p> Signup and view all the answers

    What is the time taken for depletion of Vitamin B12 stores in the body?

    <p>2-5 years</p> Signup and view all the answers

    Alcoholism is associated with __________ changes in macrocytic anemia.

    <p>normoblastic</p> Signup and view all the answers

    Match the following causes of macrocytic anemia with their corresponding changes:

    <p>Vitamin B12 deficiency = Megaloblastic Changes Liver disease = Normoblastic Changes Folate deficiency = Megaloblastic Changes Bone marrow failure syndromes = Normoblastic Changes</p> Signup and view all the answers

    Which of the following conditions is associated with low iron indices?

    <p>Iron deficiency anemia</p> Signup and view all the answers

    The Reticulocyte production index is always high in microcytic hypochromic anemia.

    <p>False</p> Signup and view all the answers

    What does MCV stand for in the context of anemia?

    <p>Mean Corpuscular Volume</p> Signup and view all the answers

    Sideroblastic anemia is associated with ______ iron indices.

    <p>high</p> Signup and view all the answers

    Match the following anemia types with their associated iron indices:

    <p>Iron deficiency anemia = Low Anemia of chronic disease = Low Sideroblastic anemia = High Thalassemia trait = High</p> Signup and view all the answers

    Which of the following correctly describes hypoproliferative anemia?

    <p>RPI is less than 2.5</p> Signup and view all the answers

    Inherited hemoglobinopathy is an example of extracorpuscular anemia.

    <p>False</p> Signup and view all the answers

    Name one example of acquired immune hemolytic anemia.

    <p>Warm autoimmune hemolytic anemia</p> Signup and view all the answers

    ____ is a type of anemia associated with high mean corpuscular volume (MCV).

    <p>Megaloblastic anemia</p> Signup and view all the answers

    Match the following types of hemolytic anemia with their classification:

    <p>Sickle cell anemia = Inherited Intracorpuscular Thalassemia = Inherited Intracorpuscular Autoimmune hemolytic anemia = Acquired Immune Extracorpuscular Microangiopathic hemolytic anemia = Acquired Non-Immune Extracorpuscular</p> Signup and view all the answers

    Which of the following is a symptom of spinal cord involvement in hemalotology?

    <p>Increase in peripheral neuropathy</p> Signup and view all the answers

    Peripheral neuropathy is more severe in cases of Vitamin B12 deficiency compared to folic acid deficiency.

    <p>True</p> Signup and view all the answers

    What is the primary treatment for Vitamin B12 deficiency?

    <p>Lifelong Vitamin B12 supplementation</p> Signup and view all the answers

    The presence of __________ in a peripheral blood smear indicates megaloblastic changes.

    <p>oval macrocytosis</p> Signup and view all the answers

    Match the investigation findings with their associated results in Vitamin B12 deficiency:

    <p>Peripheral Blood Smear = Oval macrocytosis with elevated MCV Serum gastrin levels = Increased Serum Vitamin B levels = Decreased Bone marrow = Megaloblastic</p> Signup and view all the answers

    Study Notes

    Intravascular Hemolysis

    • Occurs within blood vessels
    • Elevated lactate dehydrogenase (LDH)
    • Hemoglobin in the blood (Hemoglobinemia)
    • Increased reticulocyte count (Reticulocytosis)
    • Increased mean corpuscular volume (MCV)
    • Hemoglobin and hemosiderin in the urine
    • Decreased serum haptoglobin (most sensitive and specific indicator of hemolysis)
    • Mild unconjugated hyperbilirubinemia
    • Dark urine in acute cases
    • Chronic cases can have varying symptoms

    Causes of Intravascular Hemolysis

    • Acute onset:

      • Mismatched blood transfusions
      • Sepsis
      • Toxins
      • Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency

    • Chronic or acute on chronic onset:

      • Paroxysmal nocturnal hemoglobinuria (PNH)
      • Microangiopathic hemolytic anemia (MAHA)
        • Fragmentation hemolysis
        • Hemolytic uremic syndrome (HUS)
      • Paroxysmal cold hemoglobinuria

    Vitamin B12 Absorption

    • Primarily absorbed from animal sources
    • Stomach: Vitamin B12 binds with R-factor/Haptocorrin (found in saliva)
    • Duodenum: Pancreatic enzymes split the complex.
    • Duodenum/Jejunum: Vitamin B12 combines with Intrinsic Factor (IF) released by parietal cells.
    • Ileum: The IF-B12 complex binds with CUBAM receptors and is released into circulation.
    • Circulation: Vitamin B12 binds with Transcobalamin-a (TC-a) to form holotranscobalamin.
    • Bone marrow: Holotranscobalamin participates in hemoglobin synthesis and red blood cell maturation.

    Causes of Vitamin B12 Deficiency

    • Autoimmune:

      • Pernicious anemia:
        • Most important cause
        • Antibodies against parietal cells and IF
      • Ileal disease:
        • Crohn’s disease
        • Tropical sprue
      • Tuberculosis (TB)

    • Small Intestinal Bacterial Overgrowth (SIBO):

      • Bacteria from the large bowel migrate to the small bowel
      • Caused by:
        • Dysmotility (e.g., scleroderma, diabetes mellitus, amyloidosis)
        • Proton Pump Inhibitors (PPIs) (causing hypochlorhydria)
        • Blind loop syndrome

    • Congenital:

      • Transcobalamin-2 deficiency
      • CUBAM mutation causing Imerslund-Grasbeck syndrome (B12 deficiency + proteinuria)

    • Infection:

      • Fish tapeworm (Diphyllobothrium latum) infection

    Transcobalamin (TC)

    Type Description
    TC-1 Produced by granulocytes. Increased in myeloproliferative neoplasms (MPN), leading to proliferation of mature granulocytes.
    TC-2 Produced in all tissues (especially the liver). Plays a crucial role in vitamin B12 transport.
    TC-3 Has some role in vitamin B12 transport.

    Vitamin B12 Functions

    • Co-factor in two metabolic processes:
      • Homocysteine to Methionine
      • Methylmalonyl CoA to Succinyl CoA

    Folic Acid Metabolism

    • Site of absorption: Proximal small intestine (jejunum and duodenum).
    • In intestinal lumen:
      • Monoglutamate (major form in food) is converted to 5-methyl THFA (circulating and storage form)
      • 5-methyl THFA is converted to THFA (functional form), which is involved in 1-carbon transfer for DNA synthesis.
      • THFA requires vitamin B12 for conversion to homocysteine and then to methionine.

    Deficiency Effects of Folate and Vitamin B12

    Folate Deficiency Vitamin B12 Deficiency Vitamin B12 + Folate Deficiency
    5-methyl/THFA levels ↓ ↑ ↓
    Homocysteine levels ↑ ↑ ↑
    Methylmalonyl CoA levels ↑ ↑ ↑
    Red cell folate levels ↓ ↓ ↓
    • Folate trap: When vitamin B12 is deficient, 5-methyl THFA accumulates.

    Causes of Folate Deficiency

    • Decreased Intake (Most Common):

      • Nutritional deficiency

    • Decreased Absorption:

      • Celiac disease

    • Increased Demand:

      • Pregnancy
      • Growth
      • Hemolysis (compensatory erythropoiesis)

    • Drugs:

      • Folate antagonists (methotrexate)
      • Sulfasalazine
      • Proton Pump Inhibitors (PPIs)
      • Pyrimethamine
      • Triamterene
      • Phenytoin

    Macrocytic Anemia

    • MCV > 100 fl

    • Megaloblastic Changes (Megaloblastic Anemia):

      • Large nucleated erythroid precursors
      • Nuclear maturation lags (no chromatin condensation)
      • Causes:
        • Vitamin B12 deficiency
        • Folate deficiency
        • Drugs inhibiting DNA synthesis (cytarabine, hydroxyurea, 6-mercaptopurine)
        • Thiamine deficiency
        • Orotic aciduria (pyrimidine metabolism)

    • Normoblastic Changes:

      • Causes:
        • Bone marrow failure syndromes
        • Liver disease
        • Scurvy
        • Hypothyroidism
        • Alcoholism
        • Brisk reticulocytosis
        • Post-bleeding
        • Chronic obstructive pulmonary disease (COPD)
        • Myelodysplastic syndromes (MDS) (macro-ovalocytes) → Aplastic anemia

    Pernicious Anemia

    • Pathogenesis: Autoimmune antibodies
      • Anti-parietal cell antibody (sensitive)
      • Anti-intrinsic factor antibody (specific)
    • Vitamin B12 Deficiency:
      • Hyperchlorhydria
      • Hypergastrinemia
      • Abdominal pain
      • Ulcerations
      • Diarrhea (osmotic/secretory)

    Clinical Features of Pernicious Anemia

    • Middle-aged to elderly female
    • Often asymptomatic
    • Pallor with yellowish tinge (due to hemolytic jaundice)
    • Skin and mucosal changes:
      • Angular cheilitis
      • Atrophic glossitis with beefy-red tongue
      • Hyperpigmentation
    • Autoimmune association:
      • Addison’s disease
      • Type 1 diabetes mellitus
      • Vitiligo
    • Antral sparing with body involvement

    Bone Marrow Findings in Pernicious Anemia

    • Bone marrow smear (done in pancytopenia):

      • Dyserythropoiesis
      • Erythroid hyperplasia
      • Decreased myeloid:erythroid ratio

    • Bone marrow aspiration:

      • Megaloblasts
      • Giant metamyelocytes

    Diagnosis of Megaloblastic Anemia

    • Serum Vitamin B12 Levels:

      • 300 pg: Possible deficiency

      • 200 - 300 pg: Normal level
      • < 200 pg: Vitamin B12 deficiency

    • Measure levels of:*

    • Methylmalonyl CoA

    • Serum Folate

    • Homocysteine (all increased in vitamin B deficiency)

    • Methylmalonyl CoA (MMA): Found in urine

    • Anti-Parietal Cell Antibody: Positive in pernicious anemia.

    • Peripheral Blood Smear:

      • Features of dyserythropoiesis:

        • Megaloblasts: Abnormal shape & size of red blood cell precursors due to vitamin B deficiency.
        • Hypersegmented Neutrophils: Neutrophils with more than 5 lobes (normal 2-5 lobes). An early sign of the abnormality.
        • < 5 lobes: Neutrophils with less than 5 lobes.
        • Pseudo-Pelger-Huet cells: Abnormal neutrophils with two or three lobes instead of the normal 3-5 lobes, often seen in myelodysplastic syndromes (MDS).
        • Earliest change: More than 5 lobes in neutrophils is the first detectable morphological change.

      • Additional features:

        • Cabot rings
        • Basophilic stippling
        • Howell-Jolly bodies

    Approach to Microcytic Hypochromic Anemia

    • Lineage*

    • Single:

      • Reticulocyte production index: Low, High
      • Mean corpuscular volume (MCV): Low, High

    • Multiple

      • Reticulocyte production index: Low, High
      • Mean corpuscular volume (MCV): Low, High

    • Iron indices (Low):

      • Iron deficiency anemia
      • Anemia of chronic disease

    • Iron indices (High):

      • Sideroblastic anemia
      • Thalassemia trait

    Approach to Hemolysis

    • Hyperproliferative anemia (RPI > 2.5)*
    • Inherited vs acquired
    • Intracorpuscular vs extracorpuscular
    • Intravascular vs extravascular
    • Hypoproliferative anemia (RPI < 2.5)*
    • Low-normal MCV:
      • Iron deficiency anemia
      • Chronic disease anemia
      • Sideroblastic anemia
    • Elevated MCV:
      • Megaloblastic anemia
      • Folate deficiency
      • Orotic aciduria
      • Thiamine deficiency
      • DNA synthesis inhibiting drugs
    • Inherited Intracorpuscular*
    • Hemoglobinopathies:
      • Sickle cell anemia
      • Thalassemia
    • Membrane defects:
      • Hereditary spherocytosis
      • Elliptocytosis
    • Enzymopathies:
      • G6PD deficiency
      • Pyruvate kinase deficiency
    • Acquired Extracorpuscular*
    • Immune:
      • Autoimmune:
        • Warm and cold autoimmune hemolytic anemia (AIHA)
        • Paroxysmal cold hemoglobinuria
      • Alloimmune:
        • Hemolytic disease of the newborn (HDN)
        • Hemolytic transfusion reactions
      • Drug-induced immune hemolytic anemia
    • Non-immune:
      • Fragmentation hemolysis:
        • Microangiopathic hemolytic anemia (HUS/TTP)
      • Paroxysmal nocturnal hemoglobinuria (PNH)
      • Sepsis
      • Toxins and drugs

    Hematology Report - Pernicious Anemia

    • CNS Features (Spinal Cord Involvement):*
    • Dorsal column, lateral corticospinal and spinothalamic tract involvement
    • Peripheral neuropathy (paraesthesia of hands and feet)
    • Late changes: Involves cortex and optic nerve
    • GI Symptoms:*
    • Increased risk of cancer (more common in males)
    • Investigations:*
    • Peripheral Blood Smear:
      • Oval macrocytosis with elevated MCV
      • Dyserythropoiesis
      • Leukopenia with hypersegmented neutrophils
      • Thrombocytopenia
    • Bone marrow: Megaloblastic
    • Serology: Anti-intrinsic factor (IF) antibody
    • Serum gastrin levels: Increased
    • Serum Vitamin B12 levels: Decreased

    Treatment for Pernicious Anemia

    • Lifelong vitamin B12 supplementation (Hydroxycobalamin)
    • Regimen:
      • 1000 µg orally daily for 1 week
      • 1000 µg weekly for 1 month
      • 1000 µg monthly for life every 6-12 months
    • Response to Treatment:*
    • Reticulocyte count ↑ by Day 2-3, maximum by 6-8 days
    • MCV: Normal in 10 weeks
    • Prognosis: Good with treatment

    Differences in Folate Deficiency

    • Peripheral neuropathy (+), less severe
    • Spinal cord involvement (-)
    • Subacute combined degeneration (SCD) often not present

    Body Stores of Vitamin B12 and Folate

    Vit B12 Folic Acid
    Body stores 2-5 mg 5-10 mg
    RDA 3-7 µg/day 50 µg/day
    Time taken for depletion 2-5 years Few weeks
    • Vitamin B12 stores take longer to deplete, making deficiency less common, even in vegetarians

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    Description

    This quiz covers intravascular hemolysis, including its characteristics, causes, and associated symptoms. It also touches on the absorption of Vitamin B12, particularly from animal sources. Test your knowledge on these important medical concepts.

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