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
2
Q
Transferrin transfers iron to which tissues
A
Tissues that have Transferrin receptors, especially erythroblasts in the bone marrow
3
Q
Some iron is stored in the macrophages as which compounds
A
Ferritin and
Haemosiderin
4
Q
Is Haemosiderin water soluble or insoluble
A
Insoluble
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.)
6
Q
Iron stored as Ferritin or Haemosiderin is in the ferric (3+) or ferrous (2+) form?
A
Ferric(3+)
7
Q
Iron is contained in muscle as which compound
A
Myoglobin
8
Q
What are the changes seen in Tissue Ferritin and TfR1 in iron overload
A
Increased tissue Ferritin
Decreased TfR1
9
Q
What are the changes seen in tissue Ferritin and TfR1 in Iron deficiency
A
Tissue Ferritin decreases
TfR1 increases
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)
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
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
13
Q
Where is Hepcidin produced
A
Produced by liver cells
14
Q
What is the major hormonal regulator of iron Homeostasis
A
Hepcidin
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
16
Q
Which three proteins control Hepcidin synthesis and secretion
A
Hemojuvelin
Transferrin Receptor 2
HFE
17
Q
Decreased production of Hepcidin occurs in response to what conditions?
A
Iron deficiency
Hypoxia
Ineffective Erythropoiesis
18
Q
What is the role of Transferrin Receptor 2
A
Senses the degree of saturation of transferrin
19
Q
What is the effect of high saturation levels of Transferrin on Hepcidin
A
Stimulates Hepcidin synthesis
20
Q
What is the effect of low saturation levels of Transferrin on Hepcidin
A
Reduction in Hepcidin synthesis
21
Q
Which food is the best source of iron
A
Liver
22
Q
Normal Erythropoeisis requires how many mg/day of iron
A
20-25mg
23
Q
WHat is normal body iron stores
A
40-50mg Fe/kg
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
25
Where in the GIT is iron absorbed
Intestinal mucosal cells in the duodenum and upper jejunum absorb the iron
26
Which hereditary diseases causes an increase in iron absorption
Hereditary Haemochromatosis
27
Which form of iron favours iron absorption
Ferrous (Fe2+) form
28
List 10 factors that reduce iron absorption
```
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
```
29
What is the name if the special receptor that haem is absorbed through in the duodenum
HCP-1
Absorption of dietary heme(found only in animals)
| Protein in small intestine
30
What protein controls the export of iron from the duodenal enterocyte into portal plasma
Ferroportin
31
Which group of people are more likely to develop iron deficiency
Menstruating Female
Pregnant Female
Female (12-15)
32
What is the effect of iron deficiency on DMT- 1 expression in duodenal crypt cell
Increased expression
33
What is the effect of low Hepcidin levels in iron deficiency on Ferroportin levels
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)
34
What is the function of the Transferrin receptor 2
This senses the degree of saturation of Transferrin and is a key regulator of Hepcidin synthesis
35
True or False
When iron deficiency is developing the reticuloendothelial stores (Haemosiderin and Ferritin) become completely depleted before anemia occurs
True
36
List some signs of Anemia
```
Painless glossitis
Angular stomatitis
Koilonychia
Dysphagia (as a result of pharyngeal webs)
Pica
```
37
What are the top three causes of iron deficiency in order of prevalence
decreased dietary intake
increased demand
increased losses
38
WHat is the value of the iron daily losses, and how is iron lost
1-2mg/day
Via nails, shedding of intestinal cells, hair, urine, skin, menstruation
39
Describe the blood film in severe anemia
Hypochromic microcytic cells, with occasional target cells and pencil shaped poilkilocytes
40
What is the blood film when the iron deficiency is associated with severe folate or vitamin B12 deficiency
A ‘dimorphic‘ film
Dual population of red cells- one is macrocytic and the other microcytic and hypochromic
41
Is the level of soluble transferrin receptor (STFR) increased or decreased in iron deficiency Anemia
Increased
42
Is the serum ferritin in iron deficiency anemia, high or low
Low
43
Is the serum Ferritin in iron overload high or low
High
44
What is the level of serum Ferritin in the anemia of chronic disorders
Normal or raised
45
What is the main cause of in men and post menopausal women
Gastro intestinal blood loss
46
What is the general treatment for iron deficiency
The underlying cause is treated as far as possible
Iron is given to correct the anemia and replenish stores
47
What is the best preparation for oral iron
Ferrous sulfate which contains 67 mg of iron in each 200 mg tablets
48
Ferrous sulfate tablets are the best preparation of oral iron, when are the best given
On an empty stomach in doses spaced by at least 6 hrs
49
List 4 side effects of ferrous sulphate iron tablets
Nausea,
Abdominal pain
Constipation
Diarrhea
50
What changes should be made in administration of ferrous sulphate iron tablets if side effects occur
The side effects can be reduced by giving parenteral iron or by using a preparation of the lower Iron content example “ferrous gluconate”
51
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
Elixir
52
For patients with iron deficiency anemia oral iron therapy is usually administered how long does this treatment last
It’s a last for approximately six months which is enough time to correct the anemia and to replenish your body iron stores
53
When treating a patient with iron deficiency anemia using oral iron therapy hemoglobin should rise at a rate of......
2g/dL every 3 weeks
54
What are two types of iron therapy treatments for patients with iron deficiency anemia
Oral iron
| parenteral iron
55
List 7 reasons for Failure of response to oral iron
```
Continuing hemorrhage
Failure to take tablets
Wrong diagnosis
Mix deficiency
Iron refractory Iron deficiency anemia
Malabsorption
Use of slow release preparation
```
56
What is the safest form of parenteral iron
Ferric hydroxide sucrose (Venofer)
57
How is Ferric hydroxide - sucrose (Venofer) administered
By slow intravenous injection or infusion usually 200 mg of iron in each infusion
58
List three examples of parentral iron
```
Ferric hydroxide-sucrose (Venofer)
Iron Dextran (CosmoFer)
Iron sorbitol (Jectofer)
```
59
When is the only time that parenteral iron is administered
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
What are the characteristic features of anemia of chronic disorders
(Colour, size, anemia progression, serum TIBC, iron TIBC, sTfR, serum Ferritin, bone marrow storage)
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
What are two main causes of anemia of chronic disorders
Chronic inflammatory diseases
| Malignant diseases
62
Chronic inflammatory diseases are at cars of anemia of chronic disorders least two types of them
Infectious
| Non infectious
63
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
```
Pulmonary abscess
tuberculosis
pneumonia
Osteomyelitis
Bacterial endocarditis
```
64
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
Rheumatoid arthritis
Systemic lupus erythematosus
Sarcoidosis
Crohns disease
65
Malignant disease are a cause of Anemia of Chronic disorders, list some examples
Carcinoma
Lymphoma
Sarcoma
66
What is the pathogenesis of Anemia of Chronic disorders?
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
What is the treatment for Anemia of chronic disorders
Anemia is corrected by successful treatment of the underlying disease and does not respond to Iron therapy
68
What is sideroblastic anemia
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
What are the two types of Sideroblastic Anemia
Hereditary
| Acquired
70
Describe the hereditary inheritance of Sideroblastic Anemia
Usually occurs in males
| Transmitted by females
71
List on type of Primary Acquired Sideroblastic Anemia
Myelodysplasia
72
List one type of Secondary Acquired Sideroblastic Anemia
Other malignant diseases of the bone marrow
Drugs
Other benign condition
73
Describe the physical appearance of sideroblasts
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
What is the diagnosis for Sideroblastic Anemia
Diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts
75
What is the treatment for Sideroblastic Anemia
Pyridoxine Therapy (Vitamin B-6)
| Repeated blood transfusions
76
Why is bone marrow aspiration not a good investigation for iron overload
Because it does not give information about the parenchymal iron
77
List two examples of direct evaluation of iron status
Bone marrow aspirate
Liver Biopsy
78
What are the underlying conditions that cause increased iron absorption from diets with normal amounts of bioavailable iron
Hereditary (HFE mutation haemochromatosis
Iron loading anemias
Chronic liver disease
Porphyria Cutanea Tarda
79
What ar ethe two types of evaluation for iron stores?
Direct and Indirect
80
List clinical presentations of Iron overload
```
Increased skin pigmentation
Hepatic disease
Diabetes mellitus
Abdominal pain
Cardiac dysfunction
Arthropathy
Gonadal insufficiency
Endocrine Dysfunction
Delayed puberty
```
81
In the laboratory evaluation of Iron overload what methods are used
MRI- STANDARD (less invasive)
SQUID (superconducting quantum interference device)
Ferritin- also good
Liver Biopsy
82
What is the treatment for iron overload
Phlebotomy
| Iron chelation
83
What are the major causes of death in iron overload
Cirrhosis
| Hepatocellular carcinoma
84
List four indirect methods for evaluation of iron status
- Ferritin
- Serum iron, TIBC, saturation
- Serum transferrin receptor
- Red cell protoporphyrin
85
What is the most useful indirect measureof iron status
Ferritin
86
What is the limitation of using ferritin as an indicator of iron status
Ferritin is affected by inflammatory states. (acute phase reactant)
87
What is a disadvantage and an advantage of indirect methods of evaluating iron status?
Adv: easy and convenient
Dis: lack specificity and sensitivity
88
What are signs of iron deficiency in neonates
cognitive and behavioural changes
89
WHat are three signs of iron deficiency in children
Irritabilty , poor cognition, decline in pschomotor response
90
List thefour sequence of events leading up to and including iron deficiency anemia
- iron stores depleted
- Iron absorption incresed
- Ineffective erythropoeisis
- Iron deficiency anemia
91
List 5 differential diagnosis for microcytic hypochromic anemia
TAILS
- Thalassemia
- Anemia of chronic disease
- Iron Deficiency Anemia
- Lead Poisoning
- Sideroblastic Anemia
92
List 5 indications for parenteral iron
- 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
WHat are three main causes of iron overload
- hereditary hemochromatosis
- increased dietary intake
- chronic transfusion
