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Molecular Basis of Disease(Sem 4) > Nutritional Anaemias > Flashcards

Nutritional Anaemias Flashcards

1
Q

What is Anaemia?

A
  • A condition where the number of red blood cells is insufficient to meet the body’s physiologic needs.
  • Insufficient oxygen carrying capacity due to reduced haemoglobin
  • When the haemoglobin levels are below normal
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2
Q

What is haemoglobin ?

A

Iron containing oxygen transport Metalloprotein found within red blood cells.

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3
Q

What are the elements of blood?

A 
RBC
Platelets
Monocyte
Lymphocytes
Eosinophil
Basophil
Neutrophil
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4
Q

Describe a normal blood film

A

Round RBC with area of central pallor (central pale area)

Well haemoglobinised cells

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5
Q

What should we take into account when looking at haemoglobin levels ?

A

We should consider ages + biological gender

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6
Q

What does the maturation of RBC require?

A
  • Folic Acid & VIT B12 -DNA synthesis
  • Iron -Haemoglobin synthesis
  • Cytokines (erythropoetin)
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7
Q

What are the Anaemia mechanisms of actions -Bone Marrow

A

Failure of production-Hypoproliferation : Reticulocytopenia (We see a reduction of reticuloctyes (immature red blood cells)

Ineffective erythropoiesis (production of RBC)

Decreased Survival
Blood loss haemolysis,reticulocytosis (increase in reticulocytes)

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8
Q

What is the MSV test?

A

Mean corpuscular volume -The size of the red blood cells :

  • Microcytic (smaller than normal )
  • Normocytic (Normal size)
  • Macrocytic (Bigger than normal)
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9
Q

What are some conditions causing microcytic anaemia ?

A
  • Iron deficiency(heme deficiency )
  • Thalassamia(globin deficiency)
  • Anaemia of chronic disease
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10
Q

What are some conditions causing macrocytic anaemia ?

A 
B12 Defiency 
Folate deficiency 
Myelodysplasia
Alcohol induced
Drug induced
Liver disease
Myxoedema
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11
Q

What are some conditions causing normocytic anaemia ?

A 
Anaemia Chronic Disease
Aplastic Anaemia
Chronic renal Failure
Bone marrow infiltration
Sickle Cell disease
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12
Q

What can reticulocyte count show ?

A

This shows whether the bone marrow is able to create RBC

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13
Q

What are nutritional anaemias?

A

This is anaemia caused by lack of essential ingredients that the body acquires from food sources :

Iron deficiency
Vitamin B12 deificiency
Folate deficiency

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14
Q

Describe how Iron is used in the body

A

-Essential for oxygen transport
It is the most abundant trace element in the body
The requirement of iron for erythropoiesis varies based on gender and physiological needs.
Menstruation in woman increases the iron requirement

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15
Q

Describe the distribution of Iron in adults and how it is absorbed

A
  • Dietary Iron is absorbed in the Duodenum (1-2mg)
  • Body will produce transferrin (a transport proteins )which will carry the iron.
  • Most of the iron sits within the reticuloendothelial macrophages,RBC,liver,bone marrow ,muscles.
  • Iron loss -Sloughed mucosal cells,deqsquamation,menstruation
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16
Q

What are the different forms of iron ?

A

Two stable forms of iron :
Ferric states (3+)
Ferrous states (2+)
Most iron is in the body as circulating Hb.

Ferritin/Hemosiderin
(iron-storage complex)
(Liver,spleen,bone marrow )

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17
Q

Describe Iron Absorption

A

-It is regulated by GI mucosal cells and hepcidin
-Site : Duodenum/proximal jejunum
-Happens via the ferroprotein receptors on enterocytes
Transferred into plasma and binds to transferrin

Amount absorbed will depend on the iron type ingested.

Heme ferrous-red is absorbed more than non heme ferric forms

Heme iron makes up to 10-20% of dietary iron

Acidity of GI, iron storage levels and bone marrow activity can affect absorption.

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18
Q

Describe how Hepcidin regulates Iron.

A

Hepcidin is a regulatory protein.

Hepcidin will reduce the amount of Ferroportin receptors available.

This decreases the amount of Iron absorption.

-Hepcidin causes ferroportin internalistaion and degradation which decreases iron transfer into blood plasma from the duodenum.

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19
Q

How is Hepicidin regulated ?

A

It is feedback regulated by iron concentrations in the plasma and the liver and by erythropoietic demand for iron.

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20
Q

What are the sources of the iron which is transferred into plasma ?

A
  • Duodenum
  • Macrophaged which recycle senescent erythrocytes (ageing RBC )
  • Iron storing hepatocytes
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21
Q

What does iron replete mean ?

A

This is when iron stores are sufficient to meet functional needs and is at a level above that defined as iron deficient and below iron excess.

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22
Q

How can we assess whether a patient has sufficient iron?

A

We can carry out an iron binding test

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23
Q

What can we look for during a iron binding test ?

A 
Serum Fe 
Ferritin
Transferrin Saturation
Transferrin
Total Iron binding capacity

They can all be used together to monitor iron status of patient

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24
Q

What is Serum Fe?

A

This is a test to check how much iron is present in your serum.The serum is the liquid which is left over from the blood when RBC and Clotting factors have been removed.

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25
Q

What is Ferritin ?

A

Ferritin is the primary storage protein and providing reserve/ water soluble.
Ferritin test is a good test for this because low ferritin = low iron storage.

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26
Q

What is the Transferrin Saturation ?

A

This is the ratio of serum iron and total iron binding capacity. It reveals the % of transferrin binding sites that are occupied by iron

27
Q

What is Transferrin ?

A

This is a protein produced by the liver. Its production is inversely proportional to Fe stores. It is vital for iron transport.

28
Q

What is the Total Iron binding capacity ?

A

It is a measurement of the capacity of Transferrin to bind to iron. Indirect measurement of Transferrin

29
Q

Describe these tests and how they are useful

A

These tests are difficult tests to do and may be unreliable/Labile (can change )
The most useful is the Ferritin test.

30
Q

What information can we get from the Ferritin tests and what are some complications involving it ?

A

The Ferritin test is generally the most useful iron test to carry out.
If Ferritin is low this means that there is an iron deficiency.

However it is part of the immune system and inflammatory response in which it may be high.

In these situations, we can check for transferrin which will increase. There will be low iron transferrin saturation.

We can calculate the Transferrin ability to bind to iron which would be high.
We can then use the rest of the tests to confirm

31
Q

What would a typical laboratory result in iron deficiency anaemia look like ?

A

Ferritin - Low
TF Saturation -Low
TIBC- High
Serum Iron -Low/Normal

32
Q

What are the causes of iron deficiency ?

A

Not enough iron due to poor diet , malabsorption , increased physiological needs

Losing too much blood - blood loss, menstruation , Gi tract loss and parasites.

33
Q

How can we investigate iron deficiency?

A

A Full blood count -Hb, MCV,MCH (mean cell haemoglobin ), Reticulocyte count

Iron studies - Ferritin , Transferrin Saturation

Blood film

BMAT ( Bone marrow biopsy but very invasive ) and iron stores

34
Q

Why is ferritin useful ?

A

It can indicate issues with iron storage before more severe problems arise.
Symptoms can be picked up and you can replace iron before the person is anaemic

35
Q

What are hypochromic RBC ?

A

These are RBC which are pale and they have a big area of central pallor. Contain little haemoglobin.

36
Q

What does Reticulocytopenic mean ?

A

This means that the patient has very small amount of reticulocytes.

37
Q

What is the prevalence of iron deficiency?

A

It is mostly common in menstruating women.
Excessive blood loss is the main cause in premenopausal women.

Blood loss (may be underlying cancer )from the GI tract is the most common cause of IDA in adult men and postmenopausal women,

38
Q

What are the symptoms of Iron deficiency Anaemia?

A
  • Fatigue ,lethargy, dizziness
  • Signs -Pallor of mucous membranes, bounding pulse , systolic flow murmurs(cardiovascular problems) smooth tongue, koilonychias (nails which become concave in shape -like a spoon )
39
Q

What is B12 and folate deficiencys and what can it result in ?

A

Vitamin B12 is required for the formation of RBCs.

Folate deficiency is the lack of folic acid which works o support the body to make RBC.

These can cause macrocytic anaemia
Can cause Low Hb, high MCV and normal MCHC

40
Q

What is macrocytic anaemia?

A

Overly large red blood cells and not enough normal red blood cells.

Megaloblastic -(Low reticulocyte count )
Due to Vitamin B12/Folic acid deficiency 
Drug related (due to interference with B12 /FA metabolism )
Nonmegaloblastic (no DNA impairment has happened ) causes :
Alcoholism 
Hypothyroidism
Liver disease
Myelodysplastic syndromes
Reticulocytosis (haemolysis )
41
Q

What are the sources of Vitamin B12 ?

A

Illeum via instrinsic factor

Mainly animal and dairy produce

42
Q

What is the source of Folate ?

A

More frequent
Vegetables and Liver
Duodenum and Jejenum

43
Q

What are B12 and folate important for ?

A

Vitamin B12 is cobalamin
Folate is Folic acid

They are both important for the maturation of RBC and for DNA synthesis

They are also both required for thymidine triphosphate synthesis

44
Q

What is the difference between Megaloblastic and non Megaloblastic macrocytic anaemia ?

A

Megaloblastic changes of blood cells are seen in B12 and Folic acid deficiency.
Characterised by peripheral smear by macro ovalocytes (big and oval shaped ) and hyper segmented (normal lobes around 3-4) neutrophils.
They retain good levels of Hb but are low in the number of cells.

45
Q

What is Macrocytic myelodysplasia ?

A

This is a blood disorder which reduces the number of healthy RBCs.It causes abnormal RBC.The RBC will appear chaotic.

46
Q

How can we diagnose a Folate deficiency (blood count )

A

Not enough reticulocytes
Low folate
Low B12

47
Q

What is folate required for in the body?

A

Folate is necessary for DNA synthesis.

Adenosine, guanine, thymidine synthesis

48
Q

What are the three main folate deficiency causes?

A
  • Increased demand
  • Decreased intake
  • Decreased absorption

Folate comes from most foods with around 60-90% being lost in cooking.It is absorbed in the jejunum and the boyd has enough stores for around 3-5 months

49
Q

What are some factors which can cause increased folate demand?

A
  • Pregnancy /breast feeding
  • Infancy /growth spurts
  • Haemolysis and rapid cell turnover e.g SCD
  • Disseminated cancer
  • Urinary losses -heart failure
50
Q

What are some factors which can cause decreased intake of folate ?

A
  • Poor diet
  • Elderly
  • Chronic alcohol intake (can cause macrocytosis )
51
Q

What are some factors which can cause decreased absorption ?

A
  • Medication (folate antagonists )e.g methotrexate
  • Coeliac
  • Jejunal resection
  • Tropical sprue
52
Q

What is Vitamin B12 required for in the body ?

A

It is an essential co -factor for methylation in DNA and cell metabolism.

Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid and homocysteine

53
Q

What are some sources for Vitamin B12 ?

A

Food containing Vit B12

Animal sources :Milk , fish ,dairy.

54
Q

How does Vit B12 get absorbed ?

A

It is absorbed in the terminal ileum.

It requires intrinsic factor to get absorbed .It is created in the parietal cells in the stomach.

Transcobalamin 11 and Transcobalamin 1 transport vit B12 to tissues

55
Q

What is Pernicious Anaemia ?

A

It is an autoimmune disorder
Body creates antibody’s against the gastric parietal cells which produce intrinsic factor or the intrinsic factor itself.

Lack of B12 absorption

56
Q

How can we identify Pernicious Anaemia?

A

We can identify the presence of the antibody’s against parietal cells /intrinsic factors.
We can then treat by giving the patient direct injections of B12 into blood.

57
Q

What are other causes of B12 deficiency (Impaired absorption)

A

Pernicious Anaemia
Gastrectomy
Zollinger Ellison syndrome
Parasites

58
Q

What are some decreased intake causes of B12 deficiency ?

A
  • Vegan diet

- Malnutrition

59
Q

What are some congenital causes of B12 deficiency ?

A
  • Intrinsic factor receptor deficiency

- Cobalamin mutation C-G-1 gene

60
Q

What are some conditions which cause increased requirements of B12 ?

A

Haemolysis
HIV
Pregnancy
Growth spurts

61
Q

What medication can cause B12 deficiency ?

A

Alcohol
NO
PPI,H2
Metformin

62
Q

What would we see in a patient with B12 /folate deficiency ?

A
  • High MCV
  • Low Hb
  • Low reticulocytes
  • High LDH (lactate dehydrogenase )
  • Blood film (Macrocytes,Ovalocytes,hypersegmented nuets)
  • BMAT (Hypercellular ,megaloblastic giant metamyelocytes
  • MMA(Increased)
63
Q

What are some clinical consequences of B12 deficiency?

A

Brain : cognition, depression , psychosis
Neurology:Myelopathy,sensory changes,ataxia,spasticity
Infertility
Cardiac cardiomyopathy
Tongue :Glossitis, taste impairment
Blood :pancytopenia

64
Q

How can we treat B12 deficiency ?

A

Increasing Iron :Diet , oral , parenteral iron supplementation ,reducing period bleeding

Folic acid-oral supplements
B12 -oral vs intramuscular treatment

Molecular Basis of Disease(Sem 4) (28 decks)

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