L.6 Iron Metabolism & Disorders Flashcards
(107 cards)
1
Q
Iron absorption steps
A
- Ingestion of dietary iron
Non-heme = ferric form Fe3+
Heme = ferrous form Fe2+ - Ferric complexes of non-heme sources are not easily absorbed - gastric acid solubilizes this iron.
- Iron released from protein complexes by proteolytic enzymes in stomach.
- Ferric iron (Fe3+) reduced to ferrous state (Fe2+) at brush border of enterocytes by Dcytb
- Ferrous transported across entercyte plasma membrane into cytoplasm by DMT-1 (membrane protein)
Acidic pH of stomach facilitates transport. - In enterocyte, iron stored as ferritin
2
Q
Iron storage
A
Stored as ferritin
Lost when enterocyte is sloughed off into intestinal tract.
3
Q
Iron release from enterocytes
A
- Iron moves from enterocyte to circulation through membrane protein Ferroportin-1.
- Hephaestin oxidizes iron Fe2+ to Fe3+ form which is required for binding to apotransferrin.
4
Q
What protein regulates movement of iron into plasma by ferroportin?
A
Hepcidin
5
Q
A
6
Q
A
7
Q
What is the site in the Hb molecule where oxygen reversibly binds?
A
Iron held at the centre of the porphyrin ring
Iron is crucial for oxygen transport in hemoglobin.
8
Q
What are the two forms of iron supplied in the diet?
A
- Haem iron
- Non-Haem iron
9
Q
Where is Haem iron derived from?
A
Hb, myoglobin from food of animal origin
10
Q
What is the form of Non-Haem iron?
A
Ferric Fe+++ form
11
Q
How is Non-Haem iron converted before absorption?
A
Converted to the ferrous form
12
Q
What is the recommended daily intake of iron for a healthy diet?
A
Approx 15mg iron/day
13
Q
What amount of iron do we need to absorb daily?
A
1-2 mg/day
14
Q
List some sources of dietary iron.
A
- Red meat
- Liver
- Green vegetables
- Poultry
- Dried fruit
15
Q
What increases iron absorption in the body?
A
Foods containing ascorbic acid and muscle protein
16
Q
What can inhibit iron absorption?
A
Caffeine
17
Q
How much iron does the typical adult human body contain?
A
About 3-5 grams of iron
18
Q
What are the vital roles of iron in the body?
A
- Synthesis of haem, myoglobin, cytochromes
- Co-factor in DNA synthesis
- Connective tissue production
19
Q
What happens to excessive iron in the body?
A
It is toxic to the body.
20
Q
Where is iron primarily found in the body?
A
- Red blood cells (RCs)
- Macrophages
- Hepatocytes
- Enterocytes
21
Q
How much iron is lost from the body per day?
A
1-2 mg of iron
22
Q
What factors increase the efficiency of intestinal absorption of iron?
A
Accelerated erythropoietic activity and depletion of body iron stores
23
Q
What can result in accelerated erythrocyte production?
A
- Bleeding
- Hypoxia
- Haemolysis
24
Q
Is there a physiological mechanism for the excretion of iron?
A
No
25
Where does control of iron balance occur?
At the level of iron absorption (duodenum and jejunum)
26
What factors modify iron balance?
* Dietary excess (over supplementation)
* Inherited protein defect (haemochromatosis)
* Anaemia (ineffective erythropoiesis)
* Iatrogenic (Red Cell Transfusions)
27
What is Hepcidin?
Master iron regulating protein
28
What role does Hepcidin play in iron balance?
Regulates iron recycling/balance via interaction with ferroportin 1
29
What is the function of DMT1?
Transports iron across the enterocyte apical plasma membrane
30
What does Ferroportin 1 do?
Transports iron across the basolateral membrane of the enterocyte
31
What is the role of Hephaestin?
Facilitates cellular export of iron & oxidizes Fe2+ to Fe3+ for binding to apotransferrin
32
What is the first step in iron absorption?
Dietary iron exists in 2 forms: Non-heme (Fe3+) & Heme (Fe2+)
33
What does gastric acid do to iron?
Solubilizes this form of iron and provides an acidic environment
34
What enzyme reduces ferric iron Fe3+ to ferrous iron Fe2+?
DcytB (duodenal cytochrome b)
35
What happens to iron in the enterocyte?
* Stored as ferritin
* Transported across the basolateral membrane into the plasma
36
How is iron transported across the basolateral membrane?
By Ferroportin 1
37
What happens to iron when it enters circulation?
Oxidized by Hephaestin to Fe3+ for binding to transferrin
38
What is Transferrin?
Transports iron around the blood
39
What is the significance of transferrin saturation?
Indicates body iron status
40
What is the formula to calculate % transferrin saturation?
Serum iron/TIBC x 100%
41
How does iron enter developing RBCs?
By receptor-mediated endocytosis through TfR on the RC membrane
42
What happens to excess iron taken up by developing erythroblasts?
Stored as Ferritin
43
Where is iron stored in the body?
* Bone marrow
* Liver
* Pancreas
* Spleen
44
What is Haemosiderin?
Formed from aggregates of ferritin, found primarily in macrophages
45
What is Ferritin?
Primary iron storage protein found in the bone marrow, liver, spleen
46
What is the role of Hepcidin in iron absorption?
Inhibits absorption when iron stores are adequate
47
What factors lead to high hepcidin levels?
* Chronic kidney disease
* Dialysis
* Genetic factors
* Infectious/inflammatory disease
48
What condition is characterized by increased absorption of iron from the GI tract?
Hereditary Haemochromatosis (HH)
49
What mutation is associated with Hereditary Haemochromatosis?
C282Y mutation
50
What is the treatment for Hereditary Haemochromatosis?
Phlebotomy
51
What is the most common cause of anaemia worldwide?
Iron deficiency
## Footnote
Affects approximately 500 million people globally.
52
What type of anaemia results from iron deficiency?
Microcytic, hypochromic anaemia
## Footnote
Characterized by reduced MCV and MCH, with small and pale red cells.
53
What laboratory findings indicate iron deficiency anaemia?
Reduced Hb, RCC, MCV, MCH; normal or high RDW; abnormal RBC histogram
## Footnote
WBC can be normal or raised, and platelets can vary.
54
What does a high RDW indicate in the context of anaemia?
Anisocytosis
## Footnote
Reflects variation in red blood cell size.
55
What is the significance of the percentage of hypochromic red cells (%HRC) in iron deficiency?
Relates to iron status over the preceding 3 months; >5% suggests iron deficiency
## Footnote
%HRC indicates the proportion of erythrocytes with cellular Hb <280 g/l.
56
What are the components of a Full Blood Count (FBC) relevant for diagnosing iron deficiency anaemia?
Hb, RCC, MCV, MCH, RDW, RBC histogram, WBC, platelets
## Footnote
Each component provides insights into the presence and severity of anaemia.
57
True or False: Iron homeostasis is static and can be easily assessed with a single test.
False
## Footnote
Iron homeostasis is dynamic, making diagnosis complex.
58
Fill in the blank: The appearance of red blood cells in iron deficiency anaemia is due to a defect in _______.
Hb synthesis
## Footnote
This defect leads to the characteristic microcytic, hypochromic appearance.
59
What is the morphology of RBCs in blood film?
Microcytic, hypochromic, anisocytosis, progressively abnormal poikilocytosis (e.g. pencil-shaped cells, target cells, dacrocytes)
## Footnote
Reticulocytes are normal or increased.
60
What is the typical WBC count in blood film morphology?
Raised WBC in some cases due to over-stimulation of bone marrow
## Footnote
This may vary based on the underlying condition.
61
What are the possible platelet counts observed?
Low, normal, or high
## Footnote
The platelet count can vary depending on the underlying pathology.
62
What are the components of iron studies (Haematinics)?
* Serum iron
* Transferrin saturation
* TIBC
* Serum ferritin
## Footnote
Reference ranges for serum ferritin differ between males and females.
63
What factors can influence serum iron levels?
* Meals
* Infection
* Inflammation
* Diurnal variation
## Footnote
These factors must be considered when interpreting serum iron levels.
64
How is transferrin saturation calculated?
Serum iron/TIBC x100
## Footnote
Normal transferrin saturation is 16-50%.
65
What is the transferrin saturation level in iron deficiency?
<15%
## Footnote
This indicates a significant iron deficiency.
66
What transferrin saturation level indicates iron overload?
>55%
## Footnote
This suggests excess iron in the body.
67
What are the findings of iron studies in iron deficiency anemia (IDA)?
* Serum Iron Decreased
* TIBC Increased
* Transferrin Saturation Decreased
* Serum Ferritin Decreased
## Footnote
These findings help diagnose IDA.
68
Why is serum ferritin important in diagnosing anemia?
It differentiates IDA from other microcytic hypochromic anemias
## Footnote
Serum ferritin levels can be normal to increased in Anaemia of Chronic Disease.
69
What is the primary goal of management in iron deficiency?
Identification and treatment of the underlying cause and correction of the deficiency by therapy with inorganic iron
## Footnote
Management includes addressing blood loss and administering oral iron therapy.
70
What is a common reason for failure to respond to oral iron therapy?
Patient not taking it
## Footnote
Other reasons may include continued haemorrhage or malabsorption.
71
What should be reassessed in non-responding patients to oral iron?
The diagnosis to exclude other causes of microcytic anaemia
## Footnote
Potential causes include infections, renal or hepatic failure, underlying malignant disease, or anaemia of inflammation due to high hepcidin levels.
72
Why is laboratory monitoring important in the management of iron deficiency?
To monitor treatment response and track erythropoiesis
## Footnote
Lab findings help detect any complications during recovery.
73
What effect does oral iron treatment have on erythropoiesis?
Stimulates a burst of erythropoiesis
## Footnote
Leads to the appearance of new, normal-sized RBCs (normocytes) in circulation.
74
What potential issue can arise from rapid RBC production during iron treatment?
Folate deficiency
## Footnote
This can lead to a mixed (dimorphic) blood film.
75
What are the two distinct RBC populations observed after iron treatment or transfusion?
* Abnormal cells: microcytic, hypochromic
* Normal cells: normocytic, normochromic
## Footnote
This results in anisocytosis and anisochromasia.
76
Fill in the blank: Lab findings help track _______ during recovery from iron deficiency.
erythropoiesis
77
True or False: The presence of new normocytes indicates a successful response to iron therapy.
True
78
What does anisocytosis refer to?
Variation in size of red blood cells
## Footnote
It is often observed in mixed blood films after treatment.
79
What does anisochromasia refer to?
Variation in colour of red blood cells
## Footnote
It is also a feature seen in blood films post iron treatment.
80
What are inflammatory cytokines involved in Anaemia of Chronic Disorders?
IL-6, TNF-α, IFN-γ
## Footnote
These cytokines are released in response to chronic disease and impact iron metabolism and erythropoiesis.
81
What effect does IL-6 have on hepcidin production?
Stimulates the liver to produce hepcidin
## Footnote
Hepcidin blocks iron absorption and inhibits iron release from macrophages and hepatocytes.
82
What is the role of hepcidin in iron metabolism?
Blocks iron absorption and inhibits iron release from macrophages and hepatocytes
## Footnote
It does this by degrading ferroportin.
83
What results from the action of hepcidin in Anaemia of Chronic Disorders?
Functional iron deficiency
## Footnote
Iron is present but sequestered and unavailable for erythropoiesis.
84
How do inflammatory cytokines affect erythropoietin (EPO) production?
Suppress EPO production in the kidney
## Footnote
This reduction affects red blood cell production.
85
What is the impact of cytokines on erythroid progenitor cells?
Inhibit proliferation in the bone marrow
## Footnote
This leads to reduced red blood cell production.
86
How does chronic inflammation affect red blood cell lifespan?
Decreases RBC lifespan
## Footnote
Increased macrophage activity leads to early phagocytosis of RBCs.
87
What lab findings are associated with Anaemia of Chronic Disease?
Decreased: Hb, serum iron, transferrin saturation, TIBC; Increased: Ferritin, CRP
## Footnote
TIBC may also be normal in some cases.
88
What is the main characteristic of Hereditary Haemochromatosis (HH)?
Increased absorption of iron from the GI tract
## Footnote
This leads to iron overload in the body.
89
What role does the HFE protein play in Hereditary Haemochromatosis?
Involved in hepcidin production
## Footnote
Mutations in the HFE gene lead to decreased hepcidin production.
90
On which chromosome is the HFE gene encoded?
Chromosome 6
## Footnote
This gene is crucial for iron metabolism regulation.
91
What mutation is primarily associated with Hereditary Haemochromatosis?
C282Y mutation
## Footnote
This mutation results in a substitution of Cyt with Tyr at position 282 in HFE protein.
92
What percentage of the European population of Celtic origin is heterozygous for the C282Y mutation?
Approx 10%
## Footnote
In Ireland, the prevalence is 1 in 83.
93
What are some other mutations that cause Hereditary Haemochromatosis?
TfR2, HJV, ferroportin
## Footnote
These mutations also affect iron metabolism.
94
Fill in the blank: The C282Y mutation was identified in _______.
1996
## Footnote
This mutation is the most common cause of Hereditary Haemochromatosis.
95
What genetic mutation is associated with hereditary hemochromatosis (HH)?
Mutation in the HFE gene
## Footnote
This mutation leads to impaired regulation of hepcidin.
96
What is the role of hepcidin in iron absorption?
Hepcidin inhibits iron absorption by degrading ferroportin
## Footnote
In HH, decreased hepcidin activity results in increased ferroportin activity.
97
What are the primary organs affected by excess iron accumulation in HH?
* Liver
* Pancreas
* Heart
* Joints
* Skin
* Pituitary
## Footnote
Excess iron can cause significant damage and lead to various complications.
98
What toxic effects does excess iron have on the body?
Generates free radicals causing oxidative stress and cell damage
## Footnote
This can lead to serious health issues.
99
List some common symptoms of hereditary hemochromatosis.
* Chronic fatigue
* Diabetes mellitus
* Melanoderma
* White nails
* Flat nails
* Koilonychia
* Hepatomegaly
* Cirrhosis
* Hepatocellular carcinoma
* Joint pain
* Osteoporosis
## Footnote
Symptoms can vary in severity and presentation.
100
What is a clinical consequence of iron overload regarding transferrin?
Complete saturation of transferrin and excess non-transferrin bound iron in plasma
## Footnote
This indicates significant iron overload.
101
What harmful radicals are generated due to excess iron?
Free hydroxyl radicals
## Footnote
These radicals can damage oxygen-related tissues.
102
What are potential health complications from iron overload?
* Cardiac failure
* Liver cirrhosis
* Liver fibrosis
* Liver cancer
* Diabetes mellitus
* Infertility
* Growth failure
## Footnote
Excess iron can initiate toxicity to various organs.
103
What laboratory findings are indicative of hereditary hemochromatosis?
* FBC: Hb increased, normochromic, normocytic RBCs
* Serum Ferritin > 300-1,500ug/l
* Haemosiderin staining of Bone Marrow and liver +++
* Serum Iron increased
* % Transferrin saturation > 45%
* Demonstration of C282Y mutation by PCR
## Footnote
High transferrin saturation is one of the earliest and most sensitive signs.
104
What is the primary treatment method for hereditary hemochromatosis?
Phlebotomy
## Footnote
This method is used to reduce iron overload.
105
How often should phlebotomy be performed initially in HH treatment?
Weekly for 6 months
## Footnote
Frequency is adjusted once iron stores are exhausted.
106
What is the recommended follow-up frequency for phlebotomy after initial treatment?
Two to four units each year, continued indefinitely
## Footnote
This helps maintain safe iron levels.
107
Why is early diagnosis important in hereditary hemochromatosis?
To prevent complications like cirrhosis and hepatocellular carcinoma
## Footnote
Early intervention can significantly improve outcomes.
