Podcast
Questions and Answers
What is the most sensitive and specific test for hemolysis?
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.
Intravascular hemolysis is primarily located in the blood vessels.
True (A)
Name one common cause of acute intravascular hemolysis.
Name one common cause of acute intravascular hemolysis.
Mismatched blood transfusion
During intravascular hemolysis, the urine may show signs of ______.
During intravascular hemolysis, the urine may show signs of ______.
Match the following terms related to hemolysis with their definitions:
Match the following terms related to hemolysis with their definitions:
What is the primary reason for Vitamin B12 absorption issues in individuals?
What is the primary reason for Vitamin B12 absorption issues in individuals?
Intrinsic Factor (IF) is secreted by goblet cells in the stomach.
Intrinsic Factor (IF) is secreted by goblet cells in the stomach.
What complex forms when Vitamin B12 binds with R-factor in the stomach?
What complex forms when Vitamin B12 binds with R-factor in the stomach?
The Vitamin B12-IF complex binds with __________ receptors in the ileum.
The Vitamin B12-IF complex binds with __________ receptors in the ileum.
Match the following Vitamin B12 forms with their characteristics:
Match the following Vitamin B12 forms with their characteristics:
What is the most important cause of Vitamin B12 deficiency?
What is the most important cause of Vitamin B12 deficiency?
Vitamin B12 is absorbed only in the stomach.
Vitamin B12 is absorbed only in the stomach.
What are the two key processes in which Vitamin B12 acts as a co-factor?
What are the two key processes in which Vitamin B12 acts as a co-factor?
The infection caused by Diphyllobothrium latum is associated with Vitamin B __________ deficiency.
The infection caused by Diphyllobothrium latum is associated with Vitamin B __________ deficiency.
Match the following types of Transcobalamin with their descriptions:
Match the following types of Transcobalamin with their descriptions:
Where in the body is folic acid primarily absorbed?
Where in the body is folic acid primarily absorbed?
Vitamin B12 deficiency leads to an accumulation of 5-methyl THFA levels.
Vitamin B12 deficiency leads to an accumulation of 5-methyl THFA levels.
Name one major cause of folate deficiency.
Name one major cause of folate deficiency.
The primary form of folate found in food is __________.
The primary form of folate found in food is __________.
Match the following causes of folate deficiency with their descriptions:
Match the following causes of folate deficiency with their descriptions:
Which of the following antibodies are sensitive and specific in the pathogenesis of pernicious anemia?
Which of the following antibodies are sensitive and specific in the pathogenesis of pernicious anemia?
Pernicious anemia is associated with autoimmune conditions like Addison's disease and Type 1 Diabetes Mellitus.
Pernicious anemia is associated with autoimmune conditions like Addison's disease and Type 1 Diabetes Mellitus.
What are the characteristic clinical features of pernicious anemia?
What are the characteristic clinical features of pernicious anemia?
Pernicious anemia is often seen in _____ aged women.
Pernicious anemia is often seen in _____ aged women.
Match the findings from bone marrow smear to their descriptions in pernicious anemia:
Match the findings from bone marrow smear to their descriptions in pernicious anemia:
At what serum vitamin B12 level is a deficiency diagnosed?
At what serum vitamin B12 level is a deficiency diagnosed?
Methylmalonyl CoA levels are decreased in vitamin B12 deficiency.
Methylmalonyl CoA levels are decreased in vitamin B12 deficiency.
What characterizes Hypersegmented Neutrophils in a peripheral blood smear?
What characterizes Hypersegmented Neutrophils in a peripheral blood smear?
The presence of __________ in urine can indicate elevated Methylmalonyl CoA levels.
The presence of __________ in urine can indicate elevated Methylmalonyl CoA levels.
Match the following features of a peripheral blood smear with their descriptions:
Match the following features of a peripheral blood smear with their descriptions:
Which of the following conditions can lead to megaloblastic anemia?
Which of the following conditions can lead to megaloblastic anemia?
Thiamine deficiency is a cause of megaloblastic anemia.
Thiamine deficiency is a cause of megaloblastic anemia.
What is the time taken for depletion of Vitamin B12 stores in the body?
What is the time taken for depletion of Vitamin B12 stores in the body?
Alcoholism is associated with __________ changes in macrocytic anemia.
Alcoholism is associated with __________ changes in macrocytic anemia.
Match the following causes of macrocytic anemia with their corresponding changes:
Match the following causes of macrocytic anemia with their corresponding changes:
Which of the following conditions is associated with low iron indices?
Which of the following conditions is associated with low iron indices?
The Reticulocyte production index is always high in microcytic hypochromic anemia.
The Reticulocyte production index is always high in microcytic hypochromic anemia.
What does MCV stand for in the context of anemia?
What does MCV stand for in the context of anemia?
Sideroblastic anemia is associated with ______ iron indices.
Sideroblastic anemia is associated with ______ iron indices.
Match the following anemia types with their associated iron indices:
Match the following anemia types with their associated iron indices:
Which of the following correctly describes hypoproliferative anemia?
Which of the following correctly describes hypoproliferative anemia?
Inherited hemoglobinopathy is an example of extracorpuscular anemia.
Inherited hemoglobinopathy is an example of extracorpuscular anemia.
Name one example of acquired immune hemolytic anemia.
Name one example of acquired immune hemolytic anemia.
____ is a type of anemia associated with high mean corpuscular volume (MCV).
____ is a type of anemia associated with high mean corpuscular volume (MCV).
Match the following types of hemolytic anemia with their classification:
Match the following types of hemolytic anemia with their classification:
Which of the following is a symptom of spinal cord involvement in hemalotology?
Which of the following is a symptom of spinal cord involvement in hemalotology?
Peripheral neuropathy is more severe in cases of Vitamin B12 deficiency compared to folic acid deficiency.
Peripheral neuropathy is more severe in cases of Vitamin B12 deficiency compared to folic acid deficiency.
What is the primary treatment for Vitamin B12 deficiency?
What is the primary treatment for Vitamin B12 deficiency?
The presence of __________ in a peripheral blood smear indicates megaloblastic changes.
The presence of __________ in a peripheral blood smear indicates megaloblastic changes.
Match the investigation findings with their associated results in Vitamin B12 deficiency:
Match the investigation findings with their associated results in Vitamin B12 deficiency:
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)
- Pernicious anemia:
-
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
- Causes:
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
- Autoimmune:
- Non-immune:
- Fragmentation hemolysis:
- Microangiopathic hemolytic anemia (HUS/TTP)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Sepsis
- Toxins and drugs
- Fragmentation hemolysis:
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.
