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Essential Haematology > Iron Overload/ Deficiency > Flashcards

Iron Overload/ Deficiency Flashcards

1
Q

The transport and storage of iron is largely mediated by which three proteins

A

Transferrin
Transferrin Receptor 1 (TfR1)
Ferritin

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2
Q

Transferrin transfers iron to which tissues

A

Tissues that have Transferrin receptors, especially erythroblasts in the bone marrow

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3
Q

Some iron is stored in the macrophages as which compounds

A

Ferritin and

Haemosiderin

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4
Q

Is Haemosiderin water soluble or insoluble

A

Insoluble

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5
Q

Which of these is visible in macrophages and other cells by light microscopy after Staining

Haemosiderin or Ferritin

A

Haemosiderin
(It contains more iron than ferritin (30 versus 23%), and it forms granules large enough to be seen with the light microscope.)

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6
Q

Iron stored as Ferritin or Haemosiderin is in the ferric (3+) or ferrous (2+) form?

A

Ferric(3+)

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7
Q

Iron is contained in muscle as which compound

A

Myoglobin

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8
Q

What are the changes seen in Tissue Ferritin and TfR1 in iron overload

A

Increased tissue Ferritin

Decreased TfR1

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9
Q

What are the changes seen in tissue Ferritin and TfR1 in Iron deficiency

A

Tissue Ferritin decreases

TfR1 increases

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10
Q

How does Iron deficiency affect Iron Regulatory Protein (IRP)

A

Iron deficiency increases the ability of IRP to bind to IREs(iron response elements)

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11
Q

How does Iron overload affect Iron Regulatory Protein (IRP)

A

Iron overload decreases the ability of IRP to bind to IREs(iron response elements)

IREs: Transferrin, TfR1

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12
Q

What happens when plasma iron is raised and transferrin is saturated

A

The amount of iron transferred to parenchymal cells (liver, endocrine organs, pancreas and heart) is increased…..
…..and this is the basis of the pathological changes associated with iron loading conditions

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13
Q

Where is Hepcidin produced

A

Produced by liver cells

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14
Q

What is the major hormonal regulator of iron Homeostasis

A

Hepcidin

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15
Q

How does Hepcidin function as the major hormonal regulator of iron homeostasis

A

It inhibits iron release from macrophages, intestinal epithelial cells by its interaction with the trans membrane iron exporter ferroportin, accelerating degradation of ferroportin mRNA

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16
Q

Which three proteins control Hepcidin synthesis and secretion

A

Hemojuvelin

Transferrin Receptor 2

HFE

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17
Q

Decreased production of Hepcidin occurs in response to what conditions?

A

Iron deficiency
Hypoxia
Ineffective Erythropoiesis

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18
Q

What is the role of Transferrin Receptor 2

A

Senses the degree of saturation of transferrin

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19
Q

What is the effect of high saturation levels of Transferrin on Hepcidin

A

Stimulates Hepcidin synthesis

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20
Q

What is the effect of low saturation levels of Transferrin on Hepcidin

A

Reduction in Hepcidin synthesis

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21
Q

Which food is the best source of iron

A

Liver

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22
Q

Normal Erythropoeisis requires how many mg/day of iron

A

20-25mg

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23
Q

WHat is normal body iron stores

A

40-50mg Fe/kg

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24
Q

List 9 factors favoring absorption of iron

A 
Haem iron
Ferrous form (Fe2+)
Acids (HCl, vitamin C)
Solubizing agents (sugar, amino acids)
Iron deficiency 
Ineffective erythropoiesis
Pregnancy 
Hereditary haemochromatosis
Increased expression of ferroportin in the duodenal enetrocytes
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25
Q

Where in the GIT is iron absorbed

A

Intestinal mucosal cells in the duodenum and upper jejunum absorb the iron

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26
Q

Which hereditary diseases causes an increase in iron absorption

A

Hereditary Haemochromatosis

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27
Q

Which form of iron favours iron absorption

A

Ferrous (Fe2+) form

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28
Q

List 10 factors that reduce iron absorption

A 
Inorganic iron
Ferric Form (Fe3+)
Alkalis- antacids, pancreatic secretions
Precipitating agents- phytates, phosphates 
Iron excess
Decreased erythropoiesis
Infection 
Tea
Decreased expression of DMT-1 and ferroportin in duodenal enterocytes
Increased Hepcidin
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29
Q

What is the name if the special receptor that haem is absorbed through in the duodenum

A

HCP-1

Absorption of dietary heme(found only in animals)

Protein in small intestine

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30
Q

What protein controls the export of iron from the duodenal enterocyte into portal plasma

A

Ferroportin

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31
Q

Which group of people are more likely to develop iron deficiency

A

Menstruating Female
Pregnant Female
Female (12-15)

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32
Q

What is the effect of iron deficiency on DMT- 1 expression in duodenal crypt cell

A

Increased expression

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33
Q

What is the effect of low Hepcidin levels in iron deficiency on Ferroportin levels

A

Increase ferroportin levels in order to allow more iron to enter portal plasma

(Thus less iron is lost when the enterocyte is shed into the gut lumen from the apex of the villous)

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34
Q

What is the function of the Transferrin receptor 2

A

This senses the degree of saturation of Transferrin and is a key regulator of Hepcidin synthesis

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35
Q

True or False

When iron deficiency is developing the reticuloendothelial stores (Haemosiderin and Ferritin) become completely depleted before anemia occurs

A

True

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36
Q

List some signs of Anemia

A 
Painless glossitis
Angular stomatitis
Koilonychia
Dysphagia (as a result of pharyngeal webs)
Pica
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37
Q

What are the top three causes of iron deficiency in order of prevalence

A

decreased dietary intake
increased demand
increased losses

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38
Q

WHat is the value of the iron daily losses, and how is iron lost

A

1-2mg/day
Via nails, shedding of intestinal cells, hair, urine, skin, menstruation

39
Q

Describe the blood film in severe anemia

A

Hypochromic microcytic cells, with occasional target cells and pencil shaped poilkilocytes

40
Q

What is the blood film when the iron deficiency is associated with severe folate or vitamin B12 deficiency

A

A ‘dimorphic‘ film

Dual population of red cells- one is macrocytic and the other microcytic and hypochromic

41
Q

Is the level of soluble transferrin receptor (STFR) increased or decreased in iron deficiency Anemia

A

Increased

42
Q

Is the serum ferritin in iron deficiency anemia, high or low

A

Low

43
Q

Is the serum Ferritin in iron overload high or low

A

High

44
Q

What is the level of serum Ferritin in the anemia of chronic disorders

A

Normal or raised

45
Q

What is the main cause of in men and post menopausal women

A

Gastro intestinal blood loss

46
Q

What is the general treatment for iron deficiency

A

The underlying cause is treated as far as possible

Iron is given to correct the anemia and replenish stores

47
Q

What is the best preparation for oral iron

A

Ferrous sulfate which contains 67 mg of iron in each 200 mg tablets

48
Q

Ferrous sulfate tablets are the best preparation of oral iron, when are the best given

A

On an empty stomach in doses spaced by at least 6 hrs

49
Q

List 4 side effects of ferrous sulphate iron tablets

A

Nausea,
Abdominal pain
Constipation
Diarrhea

50
Q

What changes should be made in administration of ferrous sulphate iron tablets if side effects occur

A

The side effects can be reduced by giving parenteral iron or by using a preparation of the lower Iron content example “ferrous gluconate”

51
Q

What is the term used to describe a sweet liquid used for medical purposes to be taken orally and intended to cure one’s illness

A

Elixir

52
Q

For patients with iron deficiency anemia oral iron therapy is usually administered how long does this treatment last

A

It’s a last for approximately six months which is enough time to correct the anemia and to replenish your body iron stores

53
Q

When treating a patient with iron deficiency anemia using oral iron therapy hemoglobin should rise at a rate of……

A

2g/dL every 3 weeks

54
Q

What are two types of iron therapy treatments for patients with iron deficiency anemia

A

Oral iron

parenteral iron

55
Q

List 7 reasons for Failure of response to oral iron

A 
Continuing hemorrhage
Failure to take tablets
Wrong diagnosis
Mix deficiency
Iron refractory Iron deficiency anemia
Malabsorption
Use of slow release preparation
56
Q

What is the safest form of parenteral iron

A

Ferric hydroxide sucrose (Venofer)

57
Q

How is Ferric hydroxide - sucrose (Venofer) administered

A

By slow intravenous injection or infusion usually 200 mg of iron in each infusion

58
Q

List three examples of parentral iron

A 
Ferric hydroxide-sucrose (Venofer)
Iron Dextran (CosmoFer)
Iron sorbitol (Jectofer)
59
Q

When is the only time that parenteral iron is administered

A

Is given when there are high iron requirements as in gastrointestinal bleeding, severe menorrhagia, chronic haemodialysis, with erythropoietin therapy, and when oral iron is ineffective or impractical

60
Q

What are the characteristic features of anemia of chronic disorders
(Colour, size, anemia progression, serum TIBC, iron TIBC, sTfR, serum Ferritin, bone marrow storage)

A

Normochromic, Normocytic or mildly hypochromic
Mild non progressive anemia
Both the serum and iron TIBC are reduced (iron stores are increased therefore TIBC is decreased)
sTfR normal
Serum Ferritin normal or raised
Bone marrow storage normal

61
Q

What are two main causes of anemia of chronic disorders

A

Chronic inflammatory diseases

Malignant diseases

62
Q

Chronic inflammatory diseases are at cars of anemia of chronic disorders least two types of them

A

Infectious

Non infectious

63
Q

Chronic inflammatory diseases are causes of anemia of chronic disorders there are two types: infectious and non-infectious. List some examples of infectious causes of chronic inflammatory disease

A 
Pulmonary abscess
 tuberculosis
pneumonia
Osteomyelitis 
Bacterial endocarditis
64
Q

Chronic inflammatory diseases are causes of anemia of chronic disorders there are two types: infectious and non-infectious. List some examples of non infectious causes of chronic inflammatory disease

A

Rheumatoid arthritis
Systemic lupus erythematosus
Sarcoidosis
Crohns disease

65
Q

Malignant disease are a cause of Anemia of Chronic disorders, list some examples

A

Carcinoma
Lymphoma
Sarcoma

66
Q

What is the pathogenesis of Anemia of Chronic disorders?

A

There is decresed release of iron from macrophages, reduced red cell lifespan and an inadequate erythropoietin response to anemia. EPO (suppressed)

Hepcidin is an acute phase reactant and is increased in Chronic diseases or inflammation, as a result the ferroportin is less available to transport iron from the proximal SI

67
Q

What is the treatment for Anemia of chronic disorders

A

Anemia is corrected by successful treatment of the underlying disease and does not respond to Iron therapy

68
Q

What is sideroblastic anemia

A

This is a refractory anemia with hypochromic cells in the peripheral blood and increase marrow iron, it is defined by the presence of many pathological ring sideroblast in the bone marrow

your body’s not making use of iron in your red blood cells

69
Q

What are the two types of Sideroblastic Anemia

A

Hereditary

Acquired

70
Q

Describe the hereditary inheritance of Sideroblastic Anemia

A

Usually occurs in males

Transmitted by females

71
Q

List on type of Primary Acquired Sideroblastic Anemia

A

Myelodysplasia

72
Q

List one type of Secondary Acquired Sideroblastic Anemia

A

Other malignant diseases of the bone marrow
Drugs
Other benign condition

73
Q

Describe the physical appearance of sideroblasts

A

These are abnormal erythroblasts containing numerous iron granules arranged in a ring or collar around the nucleus (instead of the few randomly distributed iron granules seen when normal erythroblasts are stained for iron)

74
Q

What is the diagnosis for Sideroblastic Anemia

A

Diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts

75
Q

What is the treatment for Sideroblastic Anemia

A

Pyridoxine Therapy (Vitamin B-6)

Repeated blood transfusions

76
Q

Why is bone marrow aspiration not a good investigation for iron overload

A

Because it does not give information about the parenchymal iron

77
Q

List two examples of direct evaluation of iron status

A

Bone marrow aspirate
Liver Biopsy

78
Q

What are the underlying conditions that cause increased iron absorption from diets with normal amounts of bioavailable iron

A

Hereditary (HFE mutation haemochromatosis

Iron loading anemias

Chronic liver disease

Porphyria Cutanea Tarda

79
Q

What ar ethe two types of evaluation for iron stores?

A

Direct and Indirect

80
Q

List clinical presentations of Iron overload

A 
Increased skin pigmentation 
Hepatic disease
Diabetes mellitus

Abdominal pain
Cardiac dysfunction 
Arthropathy

Gonadal insufficiency 
Endocrine Dysfunction
Delayed puberty
81
Q

In the laboratory evaluation of Iron overload what methods are used

A

MRI- STANDARD (less invasive)
SQUID (superconducting quantum interference device)
Ferritin- also good
Liver Biopsy

82
Q

What is the treatment for iron overload

A

Phlebotomy

Iron chelation

83
Q

What are the major causes of death in iron overload

A

Cirrhosis

Hepatocellular carcinoma

84
Q

List four indirect methods for evaluation of iron status

A
  • Ferritin
  • Serum iron, TIBC, saturation
  • Serum transferrin receptor
  • Red cell protoporphyrin
85
Q

What is the most useful indirect measureof iron status

A

Ferritin

86
Q

What is the limitation of using ferritin as an indicator of iron status

A

Ferritin is affected by inflammatory states. (acute phase reactant)

87
Q

What is a disadvantage and an advantage of indirect methods of evaluating iron status?

A

Adv: easy and convenient

Dis: lack specificity and sensitivity

88
Q

What are signs of iron deficiency in neonates

A

cognitive and behavioural changes

89
Q

WHat are three signs of iron deficiency in children

A

Irritabilty , poor cognition, decline in pschomotor response

90
Q

List thefour sequence of events leading up to and including iron deficiency anemia

A
  • iron stores depleted
  • Iron absorption incresed
  • Ineffective erythropoeisis
  • Iron deficiency anemia
91
Q

List 5 differential diagnosis for microcytic hypochromic anemia

A

TAILS
- Thalassemia
- Anemia of chronic disease
- Iron Deficiency Anemia
- Lead Poisoning
- Sideroblastic Anemia

92
Q

List 5 indications for parenteral iron

A
  • high iron requiremnet
    -GI bleeding
    -severe menorrhagia
    -mid-late pregnancy
  • chronic hemodialysis
  • post-op after major surgery
  • malabsorption syndrome
  • intolerable side effects of oral iron
93
Q

WHat are three main causes of iron overload

A
  • hereditary hemochromatosis
  • increased dietary intake
  • chronic transfusion

Essential Haematology (14 decks)

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