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Haematology > The Nutritional Anaemias > Flashcards

The Nutritional Anaemias Flashcards

1
Q

What is anaemia?

A

Anaemia is a condition where number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient for body’s physiological needs

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2
Q

What causes the oxygen insufficiency of anaemic RBCs ?

A

Insufficient oxygen carrying capacity is due to reduced haemoglobin concentration as seen with insufficient RBC

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3
Q

What is haemoglobin?

A

Iron containing oxygen transport metalloprotein

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4
Q

What is the consequence of decreased Hb in RBCs?

A

Within RBCs

Reduction in haemoglobin = anaemia (reduction in oxygen carrying capacity)

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5
Q

What do RBCs require in order to mature?

A
  • Vitamin B12 & folic acid; DNA synthesis
  • Iron; Haemoglobin synthesis
  • Vitamins
  • Cytokines (erythropoeitin)
  • Healthy bone marrow environment
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6
Q

What mechanism failures cause anaemia to occur?

A
  1. Failure of Production: hypoproliferation,
    Reticulocytopenic
  2. Ineffective Erythropoiesis
  3. Decreased Survival: Blood loss, haemolysis,
    reticulocytosis
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7
Q

What are the different types of low Hb anaemias?

A
  • Microcytic
  • Normocytic
  • Macrocytic
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8
Q

Outline the microcytic low Hb anaemias

A
  • iron deficiency (low heme)
  • thalassaemia (globin deficiency
  • anaemia of chronic disease
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9
Q

What are the normocytic low Hb anaemias?

A
  • anaemia chronic disease
  • aplastic anaemia
  • chronic renal failure
  • bone marrow infiltration
  • sickle cell disease
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10
Q

What anaemias cause macrocytic low Hb levels?

A
  • B12 / Folate deficiency
  • myelodysplasia
  • alcohol / drug induced
  • liver disease
  • myxoedema
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11
Q

Apart from Hb what other aspect of RBCs can we look at to diagnose anaemia type?

A

Reticulocyte count then adds further clue as to failure of production or increased losses

Find out if anaemia is acquired or hereditary

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12
Q

What are nutritional anaemias?

A

Anaemia caused by lack of essential ingredients that the body acquires from food sources

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13
Q

Lack of which essential sources can lead to nutritional anaemia?

A

Iron deficiency
Vitamin B12 deficiency
Folate deficiency

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14
Q

What is the significance of iron?

A

Essential for O2 transport, Most abundant trace element in body

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15
Q

What is the daily requirement of iron?

A

Daily requirement for iron for erythropoiesis varies depending on gender and physiological needs

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16
Q

Where is the majority of iron in the body acquired from?

A

Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood)

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17
Q

How does a vegetarian diet affect Iron levels?

A

Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater

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18
Q

How is iron requirement variable between genders?

A

Women require more iron due to menstruation and especially during pregnancy

Menopausal women require ~similar amounts as men

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19
Q

What is the role of iron in the body?

A

Iron is an essential component of cytochromes, oxygen-binding molecules (i.e., haemoglobin and myoglobin), and many enzymes.

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20
Q

Where is dietary iron absorbed?

A

Dietary iron is absorbed predominantly in the duodenum

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21
Q

How does iron travel through GI system to cells?

A

Fe3+ ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin

Stored iron can be mobilized for reuse

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22
Q

Outline the average amount of iron carried by an adult male

A

Adult men normally have 35 to 45 mg of iron per kilogram of body weight

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23
Q

Why do women have lower iron levels than men?

A

Premenopausal women have lower iron stores due to recurrent blood loss through menstruation

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24
Q

Where does majority of dietary iron end up in the body?

A

More than 2/3 of body’s iron content incorporated into Hb in developing erythroid precursors and mature red cells

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25
Q

Where is the iron (not used in Hb) found?

A

Most remaining body iron is found in hepatocytes and reticuloendothelial macrophages, which serve as storage deposits

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26
Q

What is the role of reticuloendothelial macrophages?

A

Reticuloendothelial macrophages

  • ingest senescent red cells
  • catabolise Hb to scavenge iron
  • load iron onto transferrin for reuse
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27
Q

How is iron metabolism regulated?

A

Iron metabolism is unusual in that it is controlled by absorption rather than excretion.

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28
Q

How is iron ever lost?

A

Iron is only lost through blood loss or loss of cells as they slough

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29
Q

How much iron is lost on average?

A

Men and non-menstruating women lose about 1 mg of iron per day
Menstruating women lose from 0.6 to 2.5 percent more per day.

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30
Q

Describe the structure of Hb

A

Hb: 4 haem groups, 4 globin chains able to bind 4 O2

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31
Q

What are the different forms of iron in the body?

A 
>1  stable form of iron: 
Ferric states (3+) and Ferrous states (2+)
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32
Q

How is iron stored in the body?

A

Remaining Fe kept as storage and transport proteins ferritin and hemosiderin

Found in cells of liver, spleen and bone marrow

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33
Q

Where is iron absorbed?

A

Duodenum & proximal jejunum
Via ferroportin receptors on enterocytes
Transferred into plasma and binds to transferrin

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34
Q

What cells regulate iron absorption

A

Regulated by GI mucosal cells and hepcidin

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35
Q

What determines the amount of iron absorbed?

A

Amount absorbed depends on type ingested

Heme, ferrous (red meat, > than non-heme, ferric forms Heme iron makes up 10-20% of dietary iron

36
Q

What factors effect amount of iron absorbed?

A

Other foods, GI acidity, state of iron storage levels and bone marrow activity affect absorption

37
Q

What is the role of Hepcidin?

A

Hepcidin, its receptor and iron channel ferroportin control dietary absorption, storage, and tissue distribution of iron

38
Q

What is Hepcidin?

A

the iron-regulatory hormone

39
Q

How does hepcidin decrease iron transfer to blood palsma?

A

Hepcidin causes ferroportin internalization and degradation

40
Q

Which structures transfer iron to the blood plasma?

A

Iron transfer into blood plasma occurs from:

  • the duodenum
  • macrophages (involved in recycling senescent erythrocytes)
  • iron-storing hepatocytes.
41
Q

How is hepcidin activity mediated?

A

Feedback regulated by

  • [iron] in plasma and liver
  • erythropoietic iron demand
42
Q

Where is iron transported and stored?

A

Iron transported from enterocytes and then either into plasma or if excess iron stored as ferritin

43
Q

How is iron stored in plasma?

A

In plasma: attaches to transferrin and then transported to bone marrow binds to transferrin receptors on RBC precursors

44
Q

How does ferrtin and transferrin levels change during iron deficiency?

A

A state of iron deficiency will see reduced ferritin stores and then increased transferrin

45
Q

How does serum Fe levels change throughout the day?

A

Serum Fe fluctuates throughout the day depending on what you eat

46
Q

What does a lab ferritin level study tell us?

A

Low ferritin levels show iron store levels and allow diagnoses of iron deficiency

47
Q

What other factor may cause ferritin levels to increase

A

Ferritin also part of the immune system

Ferritin levels may increase due to infection and may not necessarily mean iron levels have also increased

48
Q

Outline the lab results indicating iron deficiency anaemia

A

Low Ferritin
Low TF saturation
High TIBC
Low/Norm Serum Fe

49
Q

What are the causes of Iron deficiency anaemia?

A

NOT ENOUGH IN

  • Poor Diet
  • Malabsorption
  • Increased physiological needs

LOSING TOO MUCH
- Blood loss: menstruation, GI tract loss, parasites

50
Q

Outline tests carried out to investigate IDA

A

FBC: Hb, MCV, MCH, Reticulocyte count

Iron Studies: Ferritin, Transferrin Saturation

Blood film

BMAT and Iron stores

51
Q

Describe the type of anaemia seen in IDA

A

Iron deficiency anaemia is initially normocytic and normochromic

52
Q

Describe the development of IDA

A

Before anaemia develops, iron deficiency occurs in several stages
Transferrin % saturation w/ Fe + free erythrocyte protoporphyrin values become abnormal after tissue stores are depleted of iron

Decreased {Hb] when iron is unavailable for haem synthesis

MCV and MCH aren’t abnormal for several months after tissue stores depleted of iron

53
Q

What are the lab indicators of anaemia?

A

Serum ferritin = most sensitive laboratory indicators of mild iron deficiency

Stainable iron in tissue stores is equally sensitive, but not performed in clinical practice

54
Q

Why may reticulocyte numbers be normal in IDA patients?

A

The reticulocyte count inappropriately normal, as would expect bone marrow to compensate for anaemia by producing more new red cells.

55
Q

What is anisocytosis?

A

variation of the red cell size

56
Q

What is hypochromia?

A

area of central pallor of red cells that is larger than normal, indicates a low MCHC

57
Q

Outline the prevalence of IDA

A 
World’s most common nutritional deficiency
- 2% in adult men (≤ 69 years old)
- 4% in adult men ≥ 70 years old*
- 10% in Caucasian, non-Hispanic women
- 19% in African-American women
- Common cause of referral
- Excessive menstrual losses 1st cause in premenopausal
women
58
Q

What is the most common cause of IDA in men and postmenopausal women?

A

Blood loss from the GI tract is the most common cause of IDA in adult men and postmenopausal women

59
Q

Outline the signs and symptoms of IDA

A

Symptoms
fatigue, lethargy, and dizziness

Signs
pallor of mucous membranes, 
Bounding pulse, 
systolic flow murmurs, 
Smooth tongue, koilonychias
60
Q

Describe the lab findings seen in B12/folate deficient patients

A

Macrocytic Anaemia

Low Hb and high MCV with normal MCHC

61
Q

What are the causes of macrocytic megaloblastic anaemia

A

Megaloblastic

  • Low reticulocyte count
  • Vitamin B12/Folic acid deficiency
  • Drug-related (interference with B12/FA metabolism)
62
Q

What are the causes of macrocytic non-megaloblastic anaemia?

A

Non-megaloblastic

  • Alcoholism ++
  • Hypothyroidism
  • Liver disease
  • Myelodysplastic syndromes
  • Reticulocytosis (haemolysis)
63
Q

What is the significance of B12 and folate?

A

Both important for the final maturation of RBC and for synthesis of DNA

Both needed for thymidine triphosphate synthesis

64
Q

What are the sources of B12 and folate?

A

B12: Animal and dairy produce

Folate: vegetables, liver

65
Q

Describe the characteristics of a megaloblastic blood film

A

Seen in B12 and Folic Acid deficiency.

Characterized by macro-ovalocytes and hypersegmented neutrophils

66
Q

Describe the blood film of Folate deficient patients

A

Megaloblastic anemia, with macroovalocytes and hypersegmented neutrophil

  • Reticulocytes: 20
  • Folate 0.9 (5-15)
  • B12 163 (180 – 350)
67
Q

What is the role of folate?

A

Folate required for DNA synthesis, specifically the nucleotide bases; adenine, guanine, thymidine synthesis

68
Q

Describe the blood film of a myelodysplastic patient

A

Anaemia in myelodysplastic syndrome with

several macrocytes

69
Q

How is folate acquired in to the body?

A

Folate comes from most foods with 60-90% lost in cooking

70
Q

Where is folate absorbed?

A

Absorbed in Jejunum

Body has enough stores usually for 3-5 months

71
Q

What is Vitamin B12?

A

Essential cofactor for methylation in DNA and cell metabolism

72
Q

What is the role of B12?

A

Required for the intracellular conversion of 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine

73
Q

What substance is needed for B12 absorption?

A

Requires the presence of Intrinsic Factor for absorption in terminal ileum

74
Q

Where is intrinsic factor (IF) produced?

A

IF made in Parietal Cells in stomach

75
Q

Describe the transportation of vit. B12

A

Transcobalamin II and Transcobalamin I transport vitB12 to tissues

76
Q

What are the different types of B12 Deficiency causes

A
  • Impaired absorption
  • decreased intake
  • congenital
  • increased requirement
  • medication
77
Q

What disorders cause impaired absorption of B12?

A
  • pernicious anaemia
  • gastrectomy / ileal resection
  • zollinger-ellison syndrome
  • parasites
78
Q

What kind of diets decrease B12 intake?

A

malnutrition

vegan diet

79
Q

Outline congenital causes of B12 deficiency

A
  • IF receptor deficiency

- cobalamin mutation CG1 gene

80
Q

What conditions cause patients to need an increased B12 requirement ?

A
  • haemolysis
  • HIV
  • pregnancy
  • Growth spurts
81
Q

What medications cause B12 deficiency?

A

alcohol
NO
PPI, H2 antagonists
metformin

82
Q

What are the haematological consequences of B12 deficiency?

A

High MCV
Low/Norm Hb
Low reticulocyte count

83
Q

Describe a B12 deficient blood film

A

macrocytes, ovalocytes, hypersegmented neutrophils

84
Q

Outline some of the 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
85
Q

What are the characteristics of pernicious anaemia?

A

Autoimmune disorder
Lack of IF
Lack of B12 absorption

Gastric Parietal cell antibodies
IF antibodies

86
Q

What is the basis of nutritional anaemia treatments?

A

Treat the underlying cause

87
Q

What are the treatments available for nutritional anaemic patients?

A

Iron – diet, oral, parenteral iron supplementation, stopping the bleeding

Folic Acid – oral supplements

B12 – oral vs intramuscular treatment

Haematology (8 decks)

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