Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MEH > 4a - Introduction to anaemia, B12 and folate > Flashcards

4a - Introduction to anaemia, B12 and folate Flashcards

1
Q

What is aneamia?

A

Haemoglobin outside of the reference range for the normal population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Identify some symptoms of anaemia

A

shortness of breath, tiredness, cardiac failure, palpitations, headache Sign of an underlying condition: pallor, tachycardia, tachypnoea, hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Identify the mechanisms of anaemia

A
  1. Dyserythropoiesis 2. Haemoglobin synthesis 3. Loss of Blood 4. Overactive RES - (reticuloendothelial system)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What Is erythropoiesis?

A
  • Production of RBCs in the bone marrow. Initially begin as nucleated cells; nucleus becomes smaller and is extruded.
  • Cytoplasm: blue and pink (as it becomes more haemoglobinsed)
  • Enter circulation – for about 120 days
  • Triggered by erythropoietin - produced by the kidney in response to low oxygen conditions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the purpose of the RES?

A

Old and damaged RBCs are removed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is aplastic anaemia ?

A

Bone marrow and HPSCs are damaged which causes an inability of haematopoietic stem cells to generate mature blood cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does reduced erythropoiesis arise?

A
  • Kidney damage
  • Chronic renal failure
  • Aplastic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can myelofibrosis cause anaemia?

A
  • Myelofibrosis is the production of collagen and fibrous tissue in the bone marrow reducing the space available for correct erythropoiesis to occur.
  • This causes a reduction in the haemopoetic stem cells produced
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is dyserythropoiesis?

A
  • Defective red blood cell development
  • Iron is not released for use in bone marrow
  • Reduced lifespan of red cells
  • The marrow shows a lack of response to erythropoietin.
  • Seen in: Renal disease, inflammatory conditions such as Rheumatoid arthritis, SLE, Inflammatory bowel disease (Ulcerative Colitis or Crohn’s), chronic infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the mechanisms of anaemia?

A

Bone marrow:

  • Abnormal erythropoeisis
  • Abnormal Hb synthesis

Red blood cells

  • Abnormal Function
  • Structure

Metabolism Removal - Abnormal function of the RES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What factors affect Hb synthesis

A
  • Lack of iron (haem) - Lack of B12/ folate (DNA synthesis) - Mutations in globin chain synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Categorise abnormalities of red cell membranes

A
  • Inherited (genetic) - Acquired
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Identify some inherited diseases which impact red cell membranes

A
  • Thalassemia - Hereditary spherocytosis - Hereditary elliptocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why do issues of metabolism in red cells arise in anaemia?

A
  • Red cells need ATP to keep the membrane working properly - Lipid bilayer needs to be maintained! - Red cell enzyme defects can lead to anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Identify two metabolic disorders which result in anaemia ?

A
  1. Glucose-6-phosphate dehydrogenase 2. Pyruvate kinase deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Identify some ACQUIRED abnormalities of the red cell membrane

A
  • Heart valves – become lose, cells become sheared as they go through –> produces red cell fragments - Vasculitis - MAHA (microangiopathies) – little blood clos form in small vessels as RBCs try to pass by clots they become sheared - DIC – disseminated intravascular coagulopathy
17
Q

How do ACQUIRED abnormalities of the red cell membrane result in anaemia ?

A
  • Mechanical damage to the red cells
  • Cells taken out of the circulation
18
Q

How do impairment to the normal reticuloendothelial system result in anaemia?

A
  • The spleen removes damaged (e.g. they don’t look right) or defective red cells
  • It will do this in many of the causes of anaemia already covered e.g membrane disorders, enzyme disorders, haemoglobin disorders
19
Q

Identify three situations in which the RES removes red blood cells in anaemia

A
  • Autoimmune haemolytic anaemia
  • Haemolytic anaemia
  • Myelofibrosis
20
Q

What is Haemolytic anaemia?

A
  • RBCs destroyed more quickly as they are abnormal or damaged
  • Intravascular - Can occur within the blood vessels
  • Extravascular - outside (within the RES macrophages in spleen. Liver, bone marrow)
21
Q

Describe AUTOIMMUNE HAEMOLYTIC ANAEMIA

A
  • Autoantibodies (ie Immunoglobulin -Ig – protein produced by own B lymphocytes) bind to the red cell membrane proteins
  • Cells in the RES recognise part of the antibody, attach to it and remove it and the red cell from the circulation
22
Q

Describe Myelofibrosis

A
  • Rare haemotological condtiion
  • Bone marrow gets very fibrotic - increase in reticulin/ collagen fibers
  • No more space for cells to go so there is less room for haemopoesis to happen
  • Reduced erythropoesis
  • Increased removal RES – spleen gets bigger starts removing cells
  • Patients become anaemia and have a low platelet count
23
Q

How do we evaluate anaemia ?

A
  • Mechanism
  • Size
  • Reticulocytosis
24
Q

When do we get Anaemia with reticulocytosis?

A
  1. Acute blood loss
  2. Splenic sequestration - of cells in spleen > enlarged spleen
  3. Haemolysis
25
Q

Define some ways in which haemolysis arises which causes anaemia with reticulocytosis?

A
  1. Non-Immune
  2. Mechanical - Heart valves/ Microangiopathic haeamolytic anaemia (MAHA
  3. Haemoglobinopathies
  4. Enzyme defects
  5. Membrane defects
26
Q

Define the 3 classes of Anaemia

A
27
Q

Identify some causes of primary bone marrow failure

A
  • Aplastic anaemia
  • Red cell aplasia
28
Q

Identify soem causes of secondary bone marrow failure

A

Anaemia of chronic disease

Combined haematinic deficiencies

Uraemia

Endocrine abnormalities

HIV infection

29
Q

What type of anaemia does Vitamin B12 / folate deficiency cause and descibe this?

A
  • Megaloblastic anaemia - Commonest cause of macrocytic anaemia
  • Deficiency in building blocked required for DNA synthesis
  • Characterised by asynchromonous nucleur maturation - cell division lag behind cytoplasm development, Large (“mega”) red cell precursors are released into the bloodstream with inappropriately large nuclei and open chromatin
30
Q

Describe the pathway of vitamin B12 absorption

A

•B12 binds to haptocorrin (secreted by salivary glands) –> B12 and haptocorrin molecules enter the stomach

  • Stomach has parietal cells (HCl production) (also produce intrinsic factor - produced in stomach and also passes into the small intestine) ​
  • Haptocorrin B12 factor splits apart and B12 binds to the intrinsic factor ​
  • B12 intrinsic factor complex passes down to the terminal ilium​
  • In terminal ilium – B12 is absorbed across the terminal ilium ​
  • Enters the portal blood attached to carrier portien called transcobalamin ​
  • Mainly stored in the liver and carried to areas that it is required – e.g. erythroid cells and nerve cells ​
31
Q

What is pernicious anaemia?

A

Lack of intrinsic factor in Vitamin B12 absorption

32
Q

What is folate and what does it do?

A

Folate

  • Present in most foods, yeast, liver and leafy greens
  • Absorption in the duodenum and jejunum

Function

  • Stable form: Methyl-THF
  • Dietary folates: converted to tetrohydrofolate ‘functional form’ – carbon donator, moves carbon around from diff. molecules

•THF (functional folate) essential for: thymidylate synthesis (synthesis of Thymine) - needed for DNA synthesis

​

33
Q

What is the role of vitamin B12

A
  • Important for producing the building blocks for DNA synthesis (via thymidine synthesis)
  • Produces the functional form of Folate - tetrahydrofolate
  • Vitamin B12 transfers a methyl group from FH4 to homocysteine to form methionine - to form functional THF
34
Q

What happens if there is a lack of Vitamin B12

A
  • Lack of B12 means that the methyl group cannot be moved - so we get methyl THF instead of THF
  • This traps’ folate in the stable methyl- FH4 form
  • Results in impaired thymidine synthesis
35
Q

How do a lack of Vitamin B12 and Folate cause megaloblastic anaemia?

A
  • Leads to thythymidylate deficiency
  • No thymine, uracil is incorporated into DNA instead

•DNA repair enzymes detect error and DNA strands destroyed

•Causes asynchronous maturation between nucleus and the cytoplasm

•Nucleus (lacking DNA) not fully mature

•But cytoplasm, in which RNA production and haemoglobin synthesis continues matures at the normal rate

36
Q

How do cells appear on a peripheral blood film when they show megaloblastic features

A
  • Macrocytic red cells
  • Anisopoikilocytosis (RBCs that are of different sizes and shapes) with tear drops
  • Hypersegmented neutrophils
  • Can see white cell precursors also megaloblastic anaemia

•Nucleus (lacking DNA) not fully mature

37
Q

How do we investigate megaloblastic anaemia?

A
  • Low Hb
  • High MCV (only 75%)
  • Blood film shows ‘megaloblastic’ features – large, hypersegmented neutrophils
  • High bilirubin and LDH (indicates cell turnover)
  • Check B12 and serum folate at the same time -
  • Vit B12 test is a poor test (also if borderline, repeat } If indeterminate
  • Check plasma total homocysteine (tHcy) and/or plasma methylmalonic acid (MMA) (intermediates in pathway
38
Q

How do we treat Vit B12 and Folate deficiency

A

Folate deficiency - oral folic acid recommended to pregnant women

Vitamin B12

  • Depends on the course
  • Pernicious anaemia – hydoxycobalamine
  • Instramuscular B12 not oral because they cant absorb it
39
Q
A

MEH (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions