Iron Overload/ Deficiency Flashcards
The transport and storage of iron is largely mediated by which three proteins
Transferrin
Transferrin Receptor 1 (TfR1)
Ferritin
Transferrin transfers iron to which tissues
Tissues that have Transferrin receptors, especially erythroblasts in the bone marrow
Some iron is stored in the macrophages as which compounds
Ferritin and
Haemosiderin
Is Haemosiderin water soluble or insoluble
Insoluble
Which of these is visible in macrophages and other cells by light microscopy after Staining
Haemosiderin or Ferritin
Haemosiderin
(It contains more iron than ferritin (30 versus 23%), and it forms granules large enough to be seen with the light microscope.)
Iron stored as Ferritin or Haemosiderin is in the ferric (3+) or ferrous (2+) form?
Ferric(3+)
Iron is contained in muscle as which compound
Myoglobin
What are the changes seen in Tissue Ferritin and TfR1 in iron overload
Increased tissue Ferritin
Decreased TfR1
What are the changes seen in tissue Ferritin and TfR1 in Iron deficiency
Tissue Ferritin decreases
TfR1 increases
How does Iron deficiency affect Iron Regulatory Protein (IRP)
Iron deficiency increases the ability of IRP to bind to IREs(iron response elements)
How does Iron overload affect Iron Regulatory Protein (IRP)
Iron overload decreases the ability of IRP to bind to IREs(iron response elements)
IREs: Transferrin, TfR1
What happens when plasma iron is raised and transferrin is saturated
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
Where is Hepcidin produced
Produced by liver cells
What is the major hormonal regulator of iron Homeostasis
Hepcidin
How does Hepcidin function as the major hormonal regulator of iron homeostasis
It inhibits iron release from macrophages, intestinal epithelial cells by its interaction with the trans membrane iron exporter ferroportin, accelerating degradation of ferroportin mRNA
Which three proteins control Hepcidin synthesis and secretion
Hemojuvelin
Transferrin Receptor 2
HFE
Decreased production of Hepcidin occurs in response to what conditions?
Iron deficiency
Hypoxia
Ineffective Erythropoiesis
What is the role of Transferrin Receptor 2
Senses the degree of saturation of transferrin
What is the effect of high saturation levels of Transferrin on Hepcidin
Stimulates Hepcidin synthesis
What is the effect of low saturation levels of Transferrin on Hepcidin
Reduction in Hepcidin synthesis
Which food is the best source of iron
Liver
Normal Erythropoeisis requires how many mg/day of iron
20-25mg
WHat is normal body iron stores
40-50mg Fe/kg
List 9 factors favoring absorption of iron
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
Where in the GIT is iron absorbed
Intestinal mucosal cells in the duodenum and upper jejunum absorb the iron
Which hereditary diseases causes an increase in iron absorption
Hereditary Haemochromatosis
Which form of iron favours iron absorption
Ferrous (Fe2+) form
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
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
What protein controls the export of iron from the duodenal enterocyte into portal plasma
Ferroportin
Which group of people are more likely to develop iron deficiency
Menstruating Female
Pregnant Female
Female (12-15)
What is the effect of iron deficiency on DMT- 1 expression in duodenal crypt cell
Increased expression
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)
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
True or False
When iron deficiency is developing the reticuloendothelial stores (Haemosiderin and Ferritin) become completely depleted before anemia occurs
True
List some signs of Anemia
Painless glossitis Angular stomatitis Koilonychia Dysphagia (as a result of pharyngeal webs) Pica
What are the top three causes of iron deficiency in order of prevalence
decreased dietary intake
increased demand
increased losses
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
Describe the blood film in severe anemia
Hypochromic microcytic cells, with occasional target cells and pencil shaped poilkilocytes
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
Is the level of soluble transferrin receptor (STFR) increased or decreased in iron deficiency Anemia
Increased
Is the serum ferritin in iron deficiency anemia, high or low
Low
Is the serum Ferritin in iron overload high or low
High
What is the level of serum Ferritin in the anemia of chronic disorders
Normal or raised
What is the main cause of in men and post menopausal women
Gastro intestinal blood loss
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
What is the best preparation for oral iron
Ferrous sulfate which contains 67 mg of iron in each 200 mg tablets
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
List 4 side effects of ferrous sulphate iron tablets
Nausea,
Abdominal pain
Constipation
Diarrhea
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”
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
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
When treating a patient with iron deficiency anemia using oral iron therapy hemoglobin should rise at a rate of……
2g/dL every 3 weeks
What are two types of iron therapy treatments for patients with iron deficiency anemia
Oral iron
parenteral iron
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
What is the safest form of parenteral iron
Ferric hydroxide sucrose (Venofer)
How is Ferric hydroxide - sucrose (Venofer) administered
By slow intravenous injection or infusion usually 200 mg of iron in each infusion
List three examples of parentral iron
Ferric hydroxide-sucrose (Venofer) Iron Dextran (CosmoFer) Iron sorbitol (Jectofer)
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
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
What are two main causes of anemia of chronic disorders
Chronic inflammatory diseases
Malignant diseases
Chronic inflammatory diseases are at cars of anemia of chronic disorders least two types of them
Infectious
Non infectious
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
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
Malignant disease are a cause of Anemia of Chronic disorders, list some examples
Carcinoma
Lymphoma
Sarcoma
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
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
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
What are the two types of Sideroblastic Anemia
Hereditary
Acquired
Describe the hereditary inheritance of Sideroblastic Anemia
Usually occurs in males
Transmitted by females
List on type of Primary Acquired Sideroblastic Anemia
Myelodysplasia
List one type of Secondary Acquired Sideroblastic Anemia
Other malignant diseases of the bone marrow
Drugs
Other benign condition
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)
What is the diagnosis for Sideroblastic Anemia
Diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts
What is the treatment for Sideroblastic Anemia
Pyridoxine Therapy (Vitamin B-6)
Repeated blood transfusions
Why is bone marrow aspiration not a good investigation for iron overload
Because it does not give information about the parenchymal iron
List two examples of direct evaluation of iron status
Bone marrow aspirate
Liver Biopsy
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
What ar ethe two types of evaluation for iron stores?
Direct and Indirect
List clinical presentations of Iron overload
Increased skin pigmentation Hepatic disease Diabetes mellitus Abdominal pain Cardiac dysfunction Arthropathy Gonadal insufficiency Endocrine Dysfunction Delayed puberty
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
What is the treatment for iron overload
Phlebotomy
Iron chelation
What are the major causes of death in iron overload
Cirrhosis
Hepatocellular carcinoma
List four indirect methods for evaluation of iron status
- Ferritin
- Serum iron, TIBC, saturation
- Serum transferrin receptor
- Red cell protoporphyrin
What is the most useful indirect measureof iron status
Ferritin
What is the limitation of using ferritin as an indicator of iron status
Ferritin is affected by inflammatory states. (acute phase reactant)
What is a disadvantage and an advantage of indirect methods of evaluating iron status?
Adv: easy and convenient
Dis: lack specificity and sensitivity
What are signs of iron deficiency in neonates
cognitive and behavioural changes
WHat are three signs of iron deficiency in children
Irritabilty , poor cognition, decline in pschomotor response
List thefour sequence of events leading up to and including iron deficiency anemia
- iron stores depleted
- Iron absorption incresed
- Ineffective erythropoeisis
- Iron deficiency anemia
List 5 differential diagnosis for microcytic hypochromic anemia
TAILS
- Thalassemia
- Anemia of chronic disease
- Iron Deficiency Anemia
- Lead Poisoning
- Sideroblastic Anemia
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
WHat are three main causes of iron overload
- hereditary hemochromatosis
- increased dietary intake
- chronic transfusion
