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[MBD] NoNa > Nutritional Anaemias > Flashcards

Nutritional Anaemias Flashcards

1
Q

What is Anaemia?

A

Anaemia: ↓ Hb = ↓ RBCs = ↓ oxygen-carrying capacity = cannot meet physiological needs

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2
Q

What is haemoglobin ?

A

Iron-containing, oxygen-carrying metalloprotein found within red blood cells.

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3
Q

What are the elements of blood film?

A 
RBCs
Platelets
Monocytes
Lymphocytes
Eosinophils
Basophils
Neutrophils
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4
Q

Describe a normal blood film

A
  • Round RBC with area of central pallor

- Red = Well haemoglobinised cells

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5
Q

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

A

We should consider age + sex

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6
Q

What does the maturation of RBC require?

A
  • Healthy bone marrow
  • Cytokines - erythropoetin
  • Vit B12 + Folic Acid - DNA synthesis
  • Iron - Hb synthesis
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7
Q

What are the 3 Mechanisms of Action of Anaemia? (Bone Marrow)

A
  • BM fails to produce sufficient Hb - Hypoproliferation. Reticulocytopenia = We see ↓ reticuloctyes (immature red blood cells). ↓ Hb = Healthy BM hyperproduces reticulocytes RBCs. If you are anaemic AND can’t make enough RBCs due to insufficient ingredients/incorrect instructions, ↓ reticulocytes. = reticulocytes show if production failure/↓ RBCs.
  • Ineffective erythropoiesis (production of RBC). sufficient Fe, B12, folate, incorrect instructions - anaemia of chronic disease, insufficient RBC production

-Decreased Survival
Blood loss, haemolysis, reticulocytosis (⬆ reticulocytes)

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8
Q

What is the MCV test?

A

Mean Cell Volume - Avg size of the RBCs:

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

What are some conditions causing microcytic anaemia ?

A
  • Iron deficiency (heme deficiency) = small, pale RBCs produced = ↓ MCV
  • Thalassamia (globin deficiency)
  • Anaemia of chronic disease
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10
Q

What are some conditions causing macrocytic anaemia?

A 
B12 Defiency = ⬆ MCV
Folate deficiency = ⬆ MCV
Myelodysplasia
Alcohol-induced
Drug-induced
Liver disease
Myxoedema
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11
Q

What are some conditions causing normocytic anaemia?

A 
Anaemia of 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

↓ reticulocyte count = insufficient RBC production
↑ reticulocyte count = sufficient RBC production, may be another issue e.g. haemolysis, reticulocytosis, blood loss

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13
Q

What are nutritional anaemias?

A

Nutritional anaemias = anaemia caused by lack of essential ingredients that the body acquires from food sources :

  • Iron deficiency (for Hb synth)
  • Vitamin B12 deificiency (for DNA synth)
  • Folate deficiency (for DNA synth)
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14
Q

Describe how Iron is used in the body

A
  • Essential for oxygen transport
  • Daily requirement of iron for erythropoiesis varies based on gender and physiological needs (pregnant)
  • Menstruation in women increases the iron requirement as blood lost
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15
Q

Absorption and Distribution of Iron in Adults

A
  • Dietary Iron is absorbed in the Duodenum (1-2mg/day)
  • Body produces transferrin (transport protein) which transports iron to where it is required.
  • Most of the iron sits within the RBCs, then bone marrow and reticuloendothelial macrophages and spleen, liver, muscles.
  • Iron loss - Sloughed mucosal cells from GI tract, Menstruation, Desquamation
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16
Q

What are the different forms of iron ?

A

2 stable forms of iron :
-Ferric state (3+)
-Ferrous state (2+)
Most iron is within circulating Hb.

Storage proteins = Ferritin, Hemosiderin
(iron-storage complex)
(Liver,spleen,bone marrow )

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17
Q

Describe Iron Absorption

A

-Iron Absorption is regulated by GI mucosal cells and hepcidin
-Site : Duodenum/Proximal jejunum
-Iron is absorbed via ferroprotein receptors on enterocytes
Transferred into plasma and binds to transferrin

Amount of iron absorbed depends 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, negative feedback.

⬆ Hepcidin = ⬇ Ferroportin receptors available in enterocytes,duodenum,proximaljejumen = ⬇ Iron absorption.

  • Hepcidin causes ferroportin internalistaion and degradation, which decreases iron transfer from duodenum into blood plasma.
  • Iron binds to plasma, and then binds to transferrin (transport protein) which transports iron to where needed (BM RBCs)
  • Left over iron is stored as ferritin (storage protein).
  • Do blood test to measure ferritin = indicates patient’s iron stores
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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
  • Macrophages which recycle senescent erythrocytes (ageing RBCs)
  • Iron-storing hepatocytes
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21
Q

What does iron replete mean ?

A

Iron replete: sufficient iron = hepcidin falls.
This is when iron stores are sufficient to meet functional needs and is at a level above iron deficiency 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 iron binding studies

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23
Q

What can we look for during iron binding studies?

A
  • Serum Fe
  • Ferritin
  • Transferrin
  • Transferrin Saturation
  • Total Iron binding capacity

They can all be used together to indicate 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.
Serum = the liquid which is left over from the blood after removing RBCs and Clotting factors

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25
Q

What is Ferritin ?

A
  • Ferritin is the primary storage protein for iron and provides reserve
  • Water soluble.
  • Ferritin test is a good test for this because ⬇ ferritin = ⬇ iron storage.
  • Ferritin is the best blood test for iron:
  • ⬇ ferritin = iron deficiency
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26
Q

What is the Transferrin Saturation ?

A

Transferrin Saturation = the ratio of serum iron: total iron binding capacity.
It indicates the % of transferrin binding sites that are occupied by iron

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27
Q

What is Transferrin ?

A

Transferrin = A protein produced by the liver.

Transferrin production is inversely proportional to Fe stores

Transferrin is vital for iron transport.

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28
Q

What is the Total Iron binding capacity ?

A

Total Iron binding capacity = A measurement of the capacity of Transferrin to bind to iron.

Indirect measurement of Transferrin

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29
Q

Are these tests (iron binding studies) useful?

A

Iron binding studies are difficult tests to do and may be unreliable/Labile (can change)

The most useful is the Ferritin test.

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30
Q

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

A

Ferritin test = most useful iron test to carry out.
⬇ Ferritin = iron deficiency.

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

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

We can calculate the Transferrin ability to bind to iron which is high in iron deficiency.
We can then use the rest of the tests to confirm

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31
Q

What would typical laboratory results 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 - poor diet , malabsorption (Coeliac disease, tropical sprue), ⬆ physiological needs (pregnancy)

Losing too much blood - blood loss, menstruation , GI tract blood loss, parasites.

33
Q

Iron Deficiency Investigations

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

Ferritin indicates 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

Hypochromic RBCs = RBCs which are pale
Have a larger 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

Iron deficiency 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). -Pale bc anaemic
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 to support the body to make RBC.

Vit B12/Folate deficiencies cause macrocytic anaemia = ⬇ Hb, ⬆ MCV, normal MCHC
-normal Hb within cells, fewer RBCs + bigger RBCs

40
Q

What is macrocytic anaemia?

A

Overly large red blood cells and not enough normal red blood cells.
Macrocytic anaemia = ⬆ MCV, ⬇ Hb

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

Vitamin B12

Source: Animal + dairy produce
Absorption: Illeum via instrinsic factor(IF)

42
Q

What is the source of Folate ?

A

Source: Vegetables and Liver
Absorption: Duodenum and Jejenum

More frequent

43
Q

What are B12 and folate important for ?

A

Vitamin B12 = cobalamin
Folate is Folic acid

Both important for the maturation of RBC + for DNA synthesis
+ 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 on peripheral smear by macroovalocytes (big + oval-shaped RBCs ) + hyper segmented neutrophils (normal lobes around 3-4).

Macrocytic w/o Vit B12/Folate deficiency = Big RBCs, not uniform.
-Myelodysplastic = BM produces abnormal RBCs

(They retain good levels of Hb but are low in the number of cells.)?????????

45
Q

What is Macrocytic myelodysplasia ?

A

Macrocytic myelodysplasia = A blood disorder which reduces the number of healthy RBCs.

It causes abnormal RBCs. The RBCs appear chaotic.

46
Q

How can we diagnose a Folate deficiency (blood count)?

A

Low 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 (amino acids)

48
Q

What are the 3 main folate deficiency causes?

A

1-Increased demand for RBCs
2-Decreased intake - e.g. chronic alcohol use
3-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: meat, fish, dairy.

54
Q

How does Vit B12 get absorbed ?

A

It is absorbed in the terminal ileum.

It requires intrinsic factor to be absorbed. IF is made in the parietal cells in the stomach.
Vit B12 binds to IF to be absorbed.

Transcobalamin 11 + Transcobalamin 1 transport vit B12 to tissues

55
Q

What is Pernicious Anaemia in Vit B12 deficiency?

A

-Autoimmune disorder
Body creates antibodies against the gastric parietal cells which produce intrinsic factor OR antibodies against the intrinsic factor itself = ⬇ IF

= ⬇ Vit B12 absorption

56
Q

How can we identify Pernicious Anaemia?

A

Identify presence of the antibodies against parietal cells/intrinsic factor.

Then treat by giving the patient direct injections of vit B12 into blood.
(-not orally bc can’t absorb)

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

Haematological Consequences in patients with Vit B12/Folate deficiency

A
  • High MCV
  • Low Hb
  • Low reticulocyte count
  • High LDH = RBC breakdown. BM RBCs are so abnormal that can’t survive
  • Blood film = macrocytes, ovalocytes, hypersegmented neutrophils
  • Bone Marrow Biopsy = hypercellular, megaloblastic, giant metamyelocytes, large early WBCs
64
Q

Clinical consequences of B12 deficiency?

A
  • Brain: cognition, depression , psychosis
  • Neurology: Myelopathy, sensory changes, ataxia, spasticity (SACDC)
  • Infertility
  • Cardiac cardiomyopathy
  • Tongue: Glossitis, taste impairment
  • Blood: Pancytopenia - problems with WBCs + platelets
65
Q

Sources of iron

A

Meat - contains blood

Vegetarian - non-heme iron = need twice as much for same iron

66
Q

3 main causes of anaemia

A
  • Nutritional
  • Genetic
  • Infection
67
Q

Common nutritional deficiencies causing Nutritional Anaemia

A
  • Iron deficiency
  • Vit B12 deficiency
  • Folate deficiency
68
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

69
Q

3 types of anaemia

A
  • Microcytic
  • Normocytic
  • Macrocytic
70
Q

Daily iron requirements

A
  • 7-12 months = high requirement - poor iron from maternal milk
  • 14-18yrs = females need more iron than males due to menstruation, all the way throughout adulthood until menopause
  • Pregnant = high requirement
71
Q

Amount of iron absorbed depends on

A
  • type of iron - heme, ferrous (heme iron>ferrous iron)
  • hepcidin + ferroportin activity
  • to ⬆ absorption, take vit C, avoid milk
72
Q

What level is iron regulation?

A

Iron is regulated at the level of absorption from diet - bc can’t excrete excess iron in urine/faeces

73
Q

Low Ferritin =

A

Low Ferritin = Iron Deficient

74
Q

Treating Nutritional Anaemia

A
  • Treat underlying cause
  • Iron = supplement with iron - diet, oral, stop bleeding
  • Folic acid = oral supplements
  • Vitamin B12 = oral/intramuscular treatment
75
Q

Low MCV -

High MCV -

A

Low MCV - Ferritin

High MCV - Vit B12, Folate

[MBD] NoNa (28 decks)

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