L.8 Megaloblastic Anaemia Flashcards
1
Q
What characterizes Macrocytic Anaemias?
A
Large erythrocytes, MCV > 100fL, raised MCH, normal MCHC
Macrocytic Anaemias are characterized by the presence of large red blood cells and specific laboratory findings.
2
Q
What percentage of adults show macrocytosis in routine FBC?
A
2.5-4%
Macrocytosis can be found in a small percentage of adults without necessarily indicating anaemia.
3
Q
In what percentage of cases is macrocytosis not accompanied by anaemia?
A
Up to 60%
Macrocytosis can occur without anaemia, often indicating early deficiency in B12 or folate.
4
Q
What is the most common cause of macrocytosis?
A
Alcoholism
Alcohol consumption is a significant contributor to the development of macrocytosis.
5
Q
List other causes of macrocytosis.
A
- B12 deficiency
- Folate deficiency
- Chemotherapy
- Reticulocytosis
- Liver disease
- Hypothyroidism
- Myelodysplasia
These conditions can lead to an increase in red blood cell size.
6
Q
How can Macrocytic Anaemia be classified?
A
Megaloblastic anaemia and Non-megaloblastic anaemia
The classification is based on underlying mechanisms affecting red blood cell production.
7
Q
Define Megaloblastic Anaemia.
A
Anameia commonly caused by deficiencies in Vit B12 or folate leading to ineffective haematopoiesis. Characterised by Megaloblasts which are large nucleated red blood cell (RBC) precursors with noncondensed chromatin due to impaired DNA synthesis.
The condition leads to the production of large, abnormal erythroid precursors.
8
Q
What is the cause of Megaloblastic Anaemia?
A
Deficiencies in Vitamin B12 or folic acid
These vitamins are crucial for nucleic acid synthesis and their deficiency leads to megaloblastic anaemia.
9
Q
What are megaloblasts?
A
Giant, abnormal erythroid precursors identified in the bone marrow
Their presence is a hallmark of Megaloblastic Anaemia.
10
Q
List causes of Megaloblastic Anaemia.
A
- Vitamin B12 deficiency
- Folate deficiency
- Atrophic gastritis
- Malabsorption
- HIV treatments
- Anti-convulsants
- Bone marrow disorder
These factors disrupt normal red blood cell production.
11
Q
List causes of Non-megaloblastic Anaemia.
A
- Alcoholism
- Liver disease
- Hypothyroidism
- Haemolysis
- Haemorrhage
- COPD
- Splenectomy
- Medication side effects
- Myelodysplasia
Non-megaloblastic anaemia can arise from various systemic conditions and factors.
12
Q
What can cause false elevation of macrocytic RBCs?
A
• Cold agglutinins
• Marked leucocytosis
• Hyperglycaemia
These factors can result in misleading laboratory results regarding RBC size.
13
Q
What are the clinical features of megaloblastic anaemia?
A
• Insidious onset
• Slow development of anaemia
• Few symptoms until Hb & Hct are significantly decreased
• Typical anaemic symptoms: TATT, weakness, yellow or waxy pallor
• Dyspepsia
• Glossitis
• Loss of weight and appetite
• Neurological disturbances in B12 deficiency
Neurological issues may include peripheral neuropathy.
14
Q
What is the recommended daily allowance of Vitamin B12?
A
2-5 µg
This amount varies based on individual dietary needs.
15
Q
Where is Vitamin B12 absorbed in the body?
A
Ileum
The ileum is the final section of the small intestine, crucial for nutrient absorption.
16
Q
What are the sources of Vitamin B12?
A
• Meat
• Fish
• Eggs
• Dairy
Vitamin B12 is primarily found in animal products.
17
Q
What is the body liver store of Vitamin B12?
A
3-5 mg
These stores can last for several years.
18
Q
What is the source of folic acid?
A
• Green vegetables
• Yeast
Folic acid is essential for DNA synthesis and repair.
19
Q
What is the recommended daily allowance of folic acid?
A
50-100 µg
Adequate intake is crucial for preventing certain types of anaemia.
20
Q
What is the body liver store of folic acid?
A
10-12 mg
These stores are lower compared to Vitamin B12.
21
Q
Where is folic acid absorbed in the body?
A
Duodenum & proximal segment of the small intestine
This absorption occurs shortly after food enters the small intestine.
22
Q
What is another name for Vitamin B12?
A
Cobalamin
Cobalamin is essential for red blood cell formation and neurological function.
23
Q
What is the basic structure of Vitamin B12?
A
Cobalt in the centre of a corrin ring attached to a nucleotide portion
This structure is unique among vitamins and contributes to its biological functions.
24
Q
How is Vitamin B12 synthesized in nature?
A
By micro-organisms
This synthesis occurs in the gut of some animals and in soil.
25
In which types of foods is Vitamin B12 found?
Foods of animal origin: liver, meat, fish, dairy
## Footnote
It does not occur in fruits, cereals, or vegetables.
26
What is the typical daily intake of Vitamin B12 in Western diets?
5 – 30 µg/day
## Footnote
This intake may vary based on dietary habits and preferences.
27
What is released from the salivary glands in the oral phase of Vitamin B12 absorption?
An R-protein which is a Vitamin B12 binding protein
## Footnote
The R-protein is essential for the initial binding of Vitamin B12 in the mouth.
28
What occurs during the gastric phase of Vitamin B12 absorption?
Peptic digestion occurs in the stomach at a low pH
## Footnote
This low pH helps release Vitamin B12 from food.
29
What happens to R-proteins in the duodenum?
Pancreatic proteases degrade the R proteins, releasing Vitamin B12
## Footnote
This process is crucial for the subsequent binding of Vitamin B12 to Intrinsic Factor.
30
What does the released Vitamin B12 bind to after being released from R proteins?
Intrinsic Factor (IF)
## Footnote
Intrinsic Factor is resistant to pancreatic degradation.
31
Where is Intrinsic Factor secreted from?
The parietal cells of the gastric mucosa
## Footnote
This secretion occurs in response to the presence of food.
32
What is required for the absorption of Vitamin B12?
Intrinsic Factor (IF)
## Footnote
Without Intrinsic Factor, Vitamin B12 absorption is impaired.
33
What does the IF-B12 complex resist during absorption?
Digestion
## Footnote
This resistance allows the complex to pass through the jejunum into the ileum.
34
What specific receptor does the IF-B12 complex bind to in the ileum?
Cubulin
## Footnote
Cubulin is located on the microvilli of the intestinal epithelial cells.
35
What happens to Vitamin B12 after it attaches to the Cubulin receptor?
Vitamin B12 is taken into the mucosal cell and the IF is degraded
## Footnote
This process allows for the transport of Vitamin B12 into the bloodstream.
36
What are the transport proteins for Vitamin B12 in the blood?
Transcobalamin I (TCI), Transcobalamin II (TCII), Transcobalamin III (TCIII)
## Footnote
These proteins are responsible for carrying Vitamin B12 from the mucosal cell to various tissues.
37
What is the function of Transcobalamin I (TCI)?
Produced by granulocytes – carries 75% of recycled VitB12.
## Footnote
TCI plays a significant role in the recycling process of Vitamin B12.
38
What is the primary function of Transcobalamin II (TCII)?
Mediates transfer of B12 into the tissues and binds 90% of newly absorbed B12.
## Footnote
TCII is an alpha-globulin produced in the liver, crucial for B12 transport.
39
What is the role of Transcobalamin III (TCIII)?
Found in neutrophils – does not bind significant amounts of B12.
## Footnote
Unlike TCI and TCII, TCIII has a minimal role in B12 transport.
40
What happens to the transcobalamin II/B12 complex once it binds to the receptor of a developing cell?
It is internalised, liberating Vitamin B12 and degrading transcobalamin by lysosomal enzymes.
## Footnote
This process allows for the utilization of Vitamin B12 within the cell.
41
Where is Vitamin B12 stored in the body?
Liver (50%), heart, kidney.
## Footnote
The liver is the primary storage site for Vitamin B12.
42
Name one cause of Vitamin B12 deficiency related to nutrition.
Vegans, Pregnant women on a poor diet, Malnutrition.
## Footnote
These groups may not consume enough Vitamin B12 through their diet.
43
What is a malabsorption cause of Vitamin B12 deficiency?
Pernicious anaemia (loss of IF), Gastrectomy, Crohn’s disease, Tropical sprue, Coeliac disease, Surgical resection of ileum, Drugs, Blind loop syndrome.
## Footnote
These conditions affect the body's ability to absorb Vitamin B12 effectively.
44
What can lead to impaired utilization of Vitamin B12?
TC II deficiency, Nitrous oxide inhalation.
## Footnote
These factors interfere with the body's ability to utilize Vitamin B12.
45
What is a biological competition cause of Vitamin B12 deficiency?
Intestinal parasite, Leishmaniasis, Bacterial overgrowth.
## Footnote
These organisms can consume Vitamin B12 before it reaches the ileum, leading to a deficiency.
46
What is Pernicious Anaemia (PA)?
A Megaloblastic Anaemia caused by an absence of Intrinsic Factor due to gastric atrophy.
## Footnote
It is the most common cause of Vitamin B12 deficiency.
47
What causes Pernicious Anaemia?
Presence of auto-immune antibodies to gastric parietal cells.
## Footnote
It is classified as an autoimmune disease.
48
Which population is most commonly affected by Pernicious Anaemia?
Northern Europeans, particularly women around 60 years of age.
## Footnote
Individuals with a family history of the condition and those with another autoimmune condition are also at higher risk.
49
How is Pernicious Anaemia treated?
Lifelong monthly parenteral doses of Hydroxycobalamin.
50
What is the role of Vitamin B12 (Cyanocobalamin) in metabolism?
Required as a co-factor for essential metabolic pathways.
## Footnote
It is involved in the formation of Succinyl CoA and the conversion of homocysteine to methionine.
51
What is Succinyl CoA required for?
It is required at the early stage of haem synthesis.
52
What is the significance of methionine in the body?
Required for myelin synthesis.
53
What is the function of tetrahydrofolate?
Required for DNA synthesis.
54
What are the red cell indices associated with Vitamin B12 deficiency?
Hb reduced, RCC reduced, MCV >100fL, MCH increased, MCHC normal, RBC histogram abnormal.
## Footnote
WBC can be decreased due to neutropenia, and platelets can be slightly decreased.
55
What morphological features are seen in megaloblastic anaemia?
Triad of Oval Macrocytes, Hypersegmented Neutrophils, and Howell-Jolly Bodies.
## Footnote
Red cells appear Macrocytic and Normochromic.
56
What is the normal range for Vitamin B12 assay?
160-760 ng/L.
57
What laboratory findings suggest ineffective erythropoiesis?
LDH increased, Bilirubin increased, Haptoglobin decreased, Reticulocyte count decreased.
58
What are the findings in a bone marrow examination for Vitamin B12 deficiency?
Hypercellular with large erythroblasts.
59
Fill in the blank: Pernicious Anaemia is more common in _______.
women around 60 years of age.
60
True or False: Vitamin B12 is not required for DNA synthesis.
False.
61
What is the cellular characteristic of bone marrow in megaloblastic anaemia?
Bone marrow is hypercellular
## Footnote
Hypercellular indicates an increased number of cells present in the bone marrow.
62
What percentage of erythroid precursors are megaloblasts in megaloblastic anaemia?
At least 50%
## Footnote
This indicates a significant presence of megaloblasts in the erythroid lineage.
63
What are megaloblasts?
Large nucleated erythroid precursors
## Footnote
They are indicative of impaired erythropoiesis in megaloblastic anaemia.
64
What is the most characteristic finding in megaloblastic anaemia related to erythroblasts?
Dissociation between nuclear and cytoplasmic development
## Footnote
This is referred to as nuclear-cytoplasmic asynchrony.
65
What appearance does the erythroblast nucleus maintain in megaloblastic anaemia?
Primitive appearance
## Footnote
Despite maturation and haemoglobinisation of the cytoplasm, the nucleus appears underdeveloped.
66
What is the chromatin structure in the nucleus of megaloblasts?
Loose, open chromatin
## Footnote
This reflects the abnormal maturation process in megaloblastic anaemia.
67
What types of abnormal cells are characteristic in megaloblastic anaemia?
Giant and abnormally shaped metamyelocytes and enlarged hyperpolyploid megakaryocytes
## Footnote
These abnormalities indicate ineffective hematopoiesis.
68
What happens to many abnormal immature cells in the bone marrow in megaloblastic anaemia?
They die, resulting in ineffective erythropoiesis
## Footnote
This contributes to the anemia observed in patients.
69
What is the naturally occurring form of vitamin B9?
Folate
## Footnote
Folate is essential for various bodily functions, including DNA synthesis.
70
What is the synthetic form of vitamin B9 used in supplements?
Folic acid
## Footnote
Folic acid is often used to fortify foods and is more readily absorbed than folate.
71
How does the absorption of folic acid compare to that of folate?
Folic acid is better absorbed
## Footnote
60μg of folic acid provides the same benefits as 100μg of folate.
72
What is the Recommended Dietary Allowance (RDA) of folic acid for adults?
400μg
## Footnote
50-80% of this amount is absorbed in the intestine.
73
How much folate can the liver store?
5-10mg
## Footnote
This storage capacity is important for maintaining adequate levels in the body.
74
What important role does folate play in human health?
Normal embryogenesis
## Footnote
Folate is crucial during pregnancy for fetal development.
75
In which foods is folate found abundantly?
Eggs, milk, yeast, mushrooms, and green leafy vegetables
## Footnote
Green leafy vegetables are particularly high in folate.
76
What happens to folate when food is overcooked?
It is destroyed by heat
## Footnote
This can lead to a significant loss of folate in cooked foods.
77
What are common symptoms of folate deficiency?
Fatigue, tongue swelling, growth problems, loss of appetite, mouth sores, gray hair
## Footnote
These symptoms reflect the importance of folate in cellular health.
78
What increased amounts of folate are required during pregnancy?
Due to the added stress of rapidly growing cells
## Footnote
Increased folate is essential for proper fetal development and to prevent complications.
79
What are potential consequences of folate deficiency prior to pregnancy?
Premature birth and neural tube birth defects, such as spina bifida
## Footnote
Neural tube defects are serious congenital anomalies that can impact the spinal cord and brain.
80
By what percentage did neural tube defect cases decrease in the U.S. due to folate supplements?
36%
## Footnote
This statistic highlights the effectiveness of folate supplementation in reducing birth defects.
81
What neurologic symptom associated with decreased folate can occur during pregnancy?
Restless leg syndrome
## Footnote
This condition can cause discomfort and disrupt sleep for pregnant women.
82
In what form is most folic acid found in food?
Conjugated polyglutamate form
## Footnote
This form must be converted for absorption in the body.
83
Where does absorption of folate primarily occur?
Upper small intestine, especially in the proximal jejunum
## Footnote
This area is crucial for nutrient absorption.
84
What enzyme hydrolyses polyglutamate forms of folate in the intestine?
Pteroylpolyglutamatehydrolase (PPH)
## Footnote
This enzyme converts polyglutamate to a more absorbable form.
85
What is the monoglutamate form of folate converted to within the small intestinal mucosa?
Tetrahydro-folate (THF)
## Footnote
THF is essential for various metabolic processes.
86
What is the primary storage form of folate in the liver?
Tetrahydro-folate (THF)
## Footnote
This storage is important for maintaining folate levels in the body.
87
What is the role of THF in the body?
Cofactor in DNA synthesis
## Footnote
THF is involved in the synthesis of nucleotides necessary for DNA.
88
What is the active form of folic acid?
5-MTHF (Methylene Tetrahydrofolate)
## Footnote
5-MTHF is crucial for amino acid and nucleotide metabolism.
89
What two amino acids are synthesized with the help of 5-MTHF?
Methionine from Homocysteine and Serine to Glycine
## Footnote
These processes are vital for protein metabolism and cellular function.
90
What is thymidine a precursor for?
DNA
## Footnote
Thymidine is essential for DNA structure and function.
91
What does folate deficiency inhibit in DNA synthesis?
Thymidolyate synthesis
## Footnote
This step is critical in the DNA synthesis pathway.
92
What is a consequence of inhibited thymidolyate synthesis?
Increase in homocysteine levels
## Footnote
Elevated homocysteine is associated with various health risks.
93
What are some causes of folate deficiency?
Nutritional inadequacy, malabsorption, increased requirement, drug inhibition, biologic competition
## Footnote
These factors can lead to insufficient folate levels in the body.
94
Which demographic groups are at risk for nutritional folate deficiency?
Low-income individuals, elderly people, alcoholics
## Footnote
These groups may have limited access to adequate nutrition.
95
What conditions could lead to malabsorption of folate?
Ileitis, tropical sprue, non-tropical sprue, blind loop syndrome
## Footnote
These conditions affect the intestines and nutrient absorption.
96
What diseases are associated with an increased requirement for folate?
Sickle Cell Anemia (SCA), Thalassemia, leukemia, pregnancy
## Footnote
These conditions involve rapid cell turnover and increased folate demand.
97
Name some drugs that can inhibit folate metabolism.
Oral contraceptives, long-term anticoagulant therapy, phenobarbital, antimetabolite chemotherapy
## Footnote
These medications can interfere with folate utilization in the body.
98
What biological condition can cause competition for folate absorption?
Bacterial overgrowth in the small intestine
## Footnote
This can disrupt normal nutrient absorption processes.
99
What is the primary result of folate deficiency?
Decreased synthesis of THF, required for DNA synthesis
## Footnote
THF stands for tetrahydrofolate, a critical cofactor in the synthesis of nucleotides.
100
What is impaired due to folate deficiency?
DNA synthesis is impaired due to the inability to convert dUMP to dTMP
## Footnote
dUMP stands for deoxyuridine monophosphate and dTMP stands for deoxythymidine monophosphate.
101
What are the consequences of impaired DNA synthesis in folate deficiency?
DNA fragmentation and cell death, leading to ineffective erythropoiesis
## Footnote
Ineffective erythropoiesis refers to the reduced production of red blood cells due to impaired maturation.
102
Which cell lineages are affected by folate deficiency?
All cell lineages are affected
## Footnote
This includes red blood cells, white blood cells, and platelets.
103
What does FBC stand for in the context of laboratory investigation?
Full Blood Count
## Footnote
FBC provides important information about the cellular components of blood.
104
What are the red cell indices indicative of folate deficiency?
* Hb reduced (as low as 20 - 30g/l)
* RCC reduced
* MCV >100fL
* MCH increased
* MCHC normal
* RBC Histogram abnormal
* WBC can be decreased due to neutropenia
* Platelets can be slightly decreased
## Footnote
MCV stands for mean corpuscular volume, MCH for mean corpuscular hemoglobin, and MCHC for mean corpuscular hemoglobin concentration.
105
What is the morphology seen on a blood film in folate deficiency?
* Oval Macrocytes
* Hypersegmented Neutrophils
* Howell-Jolly Bodies
* Macrocytic, Normochromic red cells
* Poikilocytosis proportional to severity of anaemia
## Footnote
Hypersegmented neutrophils are characterized by more than 5 lobes in the nucleus.
106
What do decreased reticulocyte counts indicate in folate deficiency?
Reticulocytes can be decreased on diagnosis but increase on treatment
## Footnote
Reticulocytes are immature red blood cells released from the bone marrow.
107
What are the findings in a folate assay for diagnosing deficiency?
* Serum folate assay decreased
* Red cell folate assay decreased
* Both must be decreased to diagnose folate deficiency
## Footnote
Serum folate reflects recent intake, while red cell folate reflects availability for erythropoiesis.
108
What tests are indicative of ineffective erythropoiesis?
* LDH increased
* Bilirubin increased
* Haptoglobin decreased
* Reticulocyte count decreased
## Footnote
LDH stands for lactate dehydrogenase, and haptoglobin is a protein that binds free hemoglobin.
109
What does a bone marrow examination reveal in folate deficiency?
Hypercellular bone marrow with large erythroblasts
## Footnote
Erythroblasts are immature red blood cells in the bone marrow.
110
What is a key feature of Non-Megaloblastic Anaemia on FBC?
Non-anaemic macrocytosis
## Footnote
This means that macrocytes are present without a decrease in hemoglobin.
111
What differentiates Non-Megaloblastic Anaemia from Megaloblastic Anaemia in morphology?
Hypersegmented neutrophils are NOT present
## Footnote
The absence of hypersegmented neutrophils helps distinguish between the two types of anaemia.
112
What are common causes of Non-Megaloblastic Anaemia?
* Alcoholism
* Liver Disease
* Hypothyroidism
* Stimulated Erythropoiesis by EPO mAb treatment
## Footnote
EPO mAb refers to erythropoietin monoclonal antibody treatment.
113
What treatment is given for Vitamin B12 deficiency?
Hydroxycobalamin
## Footnote
Hydroxycobalamin is a form of Vitamin B12 used in treatment.
114
What treatment is given for folate deficiency?
Folic acid given orally
## Footnote
Folic acid is the synthetic form of folate used as a dietary supplement.
