Iron, B12, and Folate Metabolism Flashcards
1
Q
Parts of the stomach?
3
A
Fundus
Body
Antrum
2
Q
What do parietal cells produce?
2
A
- Intrinsic factor (needed for B12 intestinal absorption- B12 cant absorb anything without attachment to intrinsic factor)
- Secrete gastric acid (HCL) – releases iron from heme
3
Q
What do chief cells produce?
peptic cells
A
convert pepsinogen to pepsin
digestion of proteins
4
Q
Functions of the duodenum?
2
A
- recieve bile from the liver
and pancreatic juice from the pancreas - absorbs the majority of the iron
5
Q
Funcitons of the Jejunum?
2
A
- Specialized for absorption (of a variety of substances)
- Nutrients once absorbed are
transported to the liver via
hepatic portal vein
6
Q
Eating fat produces the gall bladder to do what?
A
release bile
7
Q
Functions of the ileum?
2
A
- Absorbs Vitamin B12 (combined with intrinsic factor)
- Bile Salts that have not been
previously absorbed are absorbed here
8
Q
Two types of roles of the liver?
A
Metabolic and regulatory roles
9
Q
What does liver produce?
And what are the roles of these two substances?
A
Produces Hepcidin
-Master regulator of iron
Produces Bile
-Fat emulsifier
10
Q
What does the pancreas produce?
2
A
Protease (degrades protein)
Lipase (degreades fat)
11
Q
What will too much iron do?
A
toxic to cells
Will kill cells
12
Q
What is normal amount of iron in the body?
What percent is it in each place?
A
4-5gms in the body (2.5 gm of it are in hemoglobin)
the rest is in ferritin complexes
13
Q
How does iron naturally occur and what state does it need to be absorbed in?
How does it get to this state?
A
Iron is in plus 3 state Fe3+
To be absorbed, must be in plus 2 state
With Vitamin C becomes Fe2+ (plus 2 state)
14
Q
How do we get rid of iron?
A
No metabolic pathway to get rid of iron
Loss through bleeding, menstrual periods
15
Q
How much a day should males and females ingest?
How much do we absorb a day?
Male and Female?
A
Males 10mg per day recommended
Females 18mg per day recommended
We absorb about 1mg per day (10%)
females - 1-2mg
16
Q
Funcitons of iron?
4
A
Oxygen carrier
Oxygen storage
Energy production
Liver detoxification
17
Q
Where is oxygen stored?
A
myoglobin
18
Q
What is an oxygen carrier?
A
hemoglobin
19
Q
How does iron function in energy production?
2
A
Cytochrome (oxidative phosphorylation)
Krebs Cycle enzymes
20
Q
Where is transferrin made and what is its role?
A
liver
carries iron b/w body locations like gut, liver, bone marrow, macrophages
21
Q
How is iron taken up into the cell?
A
by tranferrin receptors
22
Q
How many iron molecules can transferrin bind and in what state?
A
can bind two Fe3 molecuels
oxidized form
23
Q
Production of transferrin is affected how with iron overload?
How about during iron deficiency?
A
decreased
increased
24
Q
What is the role of transferrin receptors?
A
Collects iron from transferrin for uptake into cells
25
List the steps in iron uptake into the cell
| 5
1. Receptor recognizes and binds transferrin
2. Receptor + transferrin endocytosed
3. Iron released into cell via Iron transporter (DMT1)
4. Receptor + transferrin return to cell surface
5. Transferrin released
26
What percentage of transferrin should be saturated with iron?
20-50%
27
If you have an iron deficieny will their be less or more iron attached to transferrin?
What about in iron overload?
less
more
28
Will there be high or low levels of soluable transferrin receptors in iron deficiency?
What about in iron overload?
high levels of soluable transferrin receptors
low levels
29
What does increasing the level of soluble transferrin receptors tell us?
The number of transferrin receptors found on the surface of cells correlates with the level of iron within cells. When the iron level drops, the cells produce more transferrin receptors. As more receptors are produced, more are cleaved from cell surfaces and enter the blood
30
What could soluble transferrin receptor help us diagnose?
iron deficiency anemia or another kind of anemia in a inflammatory state
31
Where does the majority of iron absorption take place?
duodemnum
32
What are the two main forms of iron in the body?
heme and nonheme iron
33
What is ferric and ferris iron?
```
ferric= Fe3
Ferris= Fe2
```
34
What converts Fe3 to Fe2 before it enters the duodenal cell?
DcytB (duodenal cytochrome reductase)
35
What then is Fe2 absorbed into the cell by?
DMT-1
36
Heme iron (Fe2) enters the cell by binding to an unknown duodenal receptor cell. What happens after that?
hemeoxygenase releases Fe2 from heme and it joins the LIP (labile iron pool)
37
The labile iron pool can be dangerous to cells so what does the cell do it the iron?
3
Stored by ferritan
Used by mitchondria to make heme and enzymes
Exported out of the cell(haephaestin changes Fe2to Fe3 and is released by ferroportin)
38
What regulates ferroportion and how does it do that?
hepciden and it inhbits it but moving it into the cells where it is destroyed
39
How much of serum iron is bound to transferrin?
95%
40
How do we test serum iron?
rountine blood test
41
Whats the limititation of testing a serum iron?
tests total iron, not how much is bound and unbound. Only useful if its grossly abnormal
42
How many atoms of iron can ferritin store?
4,500 (20% of its weight)
43
Name the ways Iron can be lost physiologically?
| 3
cell loss (gut/ desquamation)
Menstration (1mg/day)
pregnancy/lactation
44
Name the ways you can lose iron pathologically?
| 5
```
Bleeding
Gut
menorrhagia
surgery
gross hematuria
```
45
How would you describe loss of iron in the body?
an unregulated process
| -there are no mechanisms to up or down regulate iron loss in the body
46
How is iron homeostasis regulated then if its an unregulated process?
adjusting iron intake ourselves
47
what are old RBCs broken down by and where?
Where is it transported after this?
by macrophages in the spleen and other organs
liver and other storage sites
48
How do new blood cells get iron?
recycled from old RBCs
49
How much iron is lost in routine metabolism?
very little
50
What is intravascular hemolysis?
breakdown of red cells in the circulation
51
What does free hemoglobin bind thats taken up by the liver?
haptoglobin
52
What does heme bind that is taken up by the liver?
What happens to heme that is passing through the kidney?
hemopexin
reabsorbed
53
What are the three mechanisms to conserve iron in pathological situations?
Free hemoglobin binds haptoglobins -> taken up by liver
Free heme binds hemopexin -> taken up by liver
Heme passing through kidney reabsorbed
54
How much iron is absorbed each day?
How much leaves the body each day?
How much of dietary iron is absorbed?
1-2mg
1-2mg
10%
55
What happens when there is increased iron absorption in the body?
5
```
Low dietary iron
Low body iron stores *
Increased red cell production *
Low hemoglobin *
Low blood oxygen content *
```
56
How would increased iron absorption affect hepcidin production?
decreased hepcidin production (increase ferripotin)
57
What happens when there is decreased iron absorption in the body?
Systemic inflammation
58
How would decreased iron absorption affect hepcidin production?
Leads to increased hepcidin production (decrease ferripotin)
59
What controls gut iron absorption?
What detects the amount of iron in the body?
What regulates hepcidin?
hepciden produced by the liver
HFE
hemojuvelin
60
What is the function of Hepcidin?
Inactivates ferroportin
--Stops iron getting out of gut cells (blocks iron release in all cells)
--Iron lost in stool when gut cells shed
DECREASES IRON ABSORPTION
61
On what three cells in ferroportin found on?
gut cells, liver cells and macrophages
62
What are the cofactors that oxidize iron to bind to transferrin?
2
Hephestin in gut
| Ceruloplasmin in other cells
63
What are the three causes of iron deficiency?
Due to reduced intake, increased loss or increased demands
64
Laboratory changes that identify iron deficiency?
| 6
```
Low iron (poor specificity)
Low ferritin (excellent specificity)
Elevated Transferrin (TIBC)
Low transferrin saturation
Hypochromia, microcytosis
Anemia
```
65
What are the three stages leading to iron deficiency?
Reduced iron stores
Iron deficient erythropoiesis
Iron deficient anemia
66
What is hemochromatosis?
iron overload
67
What is hemosiderin?
extra iron in ferritin (nutritional form)
68
Where does the iron deposit in hemosiderin? 4 (and name its associated illness)
Liver (cirrhosis)
Pancreas (diabetes)
Joints (arthritis)
Skin (dermatitis)
69
Why did hemochromatosis evolve?
| 2
1. In times of low iron the body would store up iron to sustain body function
2. Bacteria and infection need iron to survive so we learned to need low iron to defend ourselves)
70
Why is hemochromatosis helpful?
| 2
1. helps protect against malaria, plague, and TB
| 2. helped humans with low iron diets to survive long enough to reproduce
71
What is the hemochromatosis gene and is it recessive or dominant?
C282Y
| autosomal recessive
72
Cardiac and blood symptoms of hemochromatosis?
| 3
cardiomyopathy
hyperferritinemia
electrocardiographic abnormalities
73
Skin symptoms of hemochromatosis?
| 2
skin bronzing
| skin hyper pigmentation
74
Reproductive symptoms of hemochromatosis?
| 2
Loss of libido
| Impotence in males
75
General systemic symptoms of hemochromatosis?
| 6
```
Anthralgia
Fatigue
Abnormalities in the liver
Weakness
Lethargy
Diabetes Mellitus
```
76
Does a high serum ferritin level mean we have hemochromatosis?
No. they could rise in inflammation too
77
When is the only time a liver biopsy is done to test for hemochromatosis?
Pts with normal genetic testign and abnormal serum ferritan level testing
78
What does Vitamin B12 (cobalamin) have a key role in?
| 3
1. Normal functioning of the brain and nervous system
2. Formation of blood
3. Normally involved in the metabolism of every cell of the human body especially affecting DNA synthesis and regulation
1. brain and nervous functioning
2. blood formation
3. Cell metabolism
79
Is B12 (cobalamin) water or lipid soluble?
water soluble
80
How does B12 affect folate?
plays a role in recycling folate
81
What does folate do?
| 2
1. Folates support red blood cell production
2. Helps prevent homocysteine build up in blood
- -High levels leads to inflammation/coronary heart disease
82
What essential amino acid does B12 help make?
Methionine
83
Vitamin B12 is present in the liver in 3 forms. what are they?
Methylcobalamin, adenosylcobalamin
| hydroxycobalamin
84
What is B12 required for inside the cell?
What does the lack of it cause?
DNA synthesis
Lack causes failure of nuclear maturation and cell division
85
How much B12 is required per day?
5 ug (micrograms
86
Vitamin B12 and folate deficiency have the same symptoms. What might differentiate them?
B12 deficiency has neurological symptoms, folate doesn't
Dont give folate alone
87
What is a blood disorder characterized by anemia, with red blood cells that are larger than normal. This condition usually results from a deficiency of folic acid or of vitamin B-12.
Megaloblastic anemia
88
What will you notice about white blood cells in a CBC in megaloblastic anemia?
Hypersegmented neutrophils on CBC
89
If you see vitamin B12 deficiency in neurologic disorder what would you think the pathology was?
2
1. probably secondary deficiency of methionine deprivation in the nerves.
2. Paraesthesia
90
Whats Homocysteinuria?
What can it cause?
3
inherited disorder of the metabolism of the amino acid methionine (B12 helps synthesize methionine)
1. Kyphosis (hunchback of Notre Dame)
2. Lens adaptation
3. Atherosclerosis (leads to MI)-not a strong associated
91
B12 absorption occurs in two phases. What are the names of these phases and describe them?
After absorption where is the B12 delivered and/or absorbed?
The gastric phase
--IF (Intrinsic factor) binds to B12
The intestinal phase
--IF-B12 complex is absorbed in the ileum through specific llieal receptors.
blood and liver
92
What in your diet would cause a B12 deficiency?
a vegan diet (comes from meat)
93
What would cause a B12 deficiency that is caused by impaired absorption of B12?
10
1. Lack of IF in the stomach
2. Gastric surgery
3. Surgical removal of the ileum
4. Crohns disease, IBS, Ulcerative Colitis
5. Bacterial overgrowth in ileum
6. Pancreatic insufficiency (chronic pancreatitis)
7. Metformin (Common diabetic oral medication)
8. Autoimmune disorders eg
9. Graves or Lupus
10. ETOH abuse
94
Whats the underlying abnormality in pernicious anemia?
| 3
1. Underlying abnormality is an atrophic gastric mucosa
2. Failure to secrete normal gastric secretions INCLUDING intrinsic factor
3. Parietal cells of gastric glands secrete intrinsic factor (a glycoprotein) which is ESSENTIAL for absorption of B-12
95
What is B9?
Folate (Folic Acid)
96
What is a folate deficiency called? And what is it a risk factor for?
Hyperhomocysteinemia, a risk factor for cardiovascular diseases
97
Caused of folate deficiency?
| 5
1. Inadequate intake
2. Impaired absorption
3. Impaired metabolism
4. Increased demand (e.g., pregnancy and lactation)
5. The deficiency in elderly: poor diet and poor absorption
98
Drug causes of folate deficiency?
omeprazole (ppi for gerd)
| OTC H2 blockers (Tagamet, Ranitidine)
99
What is the mechanism by which omeprazole reduces folate?
1. Reduces iron absorption if taken at same time
2. Reduces acidity which in turn reduces iron absorption
3. Also reduces magnesium absorption
100
What three things do OTC H2 blockers reduce?
Reduces absorption of iron, folate &B12
101
What do lab results describe when they are talking about erythropoietic changes?
RBC morphology
Color
Size
Example: macrocytic, hyperchromtic, pale, smaller, less hemoglobin
102
What are drastically smaller RBC (less than 7 microns) indicative of iron deficiency?
Microcytes
103
What are larger RBCs (>8.5 microns in diameter) indicative of megaloblastic anemias and aplastic anemias?
Macrocytes
104
What are young RBCs seen in severe anemia?
Polychromasia
105
What are cells have decreased hgb content has increased central pallor indicative iron deficiency anemia?
Hypochromasia
106
What do target cells or codocytes, (bulls eye cells) associated with?
5
1. Liver disease,
2. hemoglobin SC,
3. thalassemia,
4. Fe deficiency,
5. asplenia
107
What are Elliptocytes/ Ovalcytes: Oval shaped elongated RBCs
associated with?
5
1. Hereditary elliptocytosis,
2. megaloblastic anemia,
3. myelofibrosis,
4. iron deficiency,
5. MDS
108
What is a dacrocyte (tear drop cell) associated with?
| 3
1. Myelofibrosis,
2. thalassemia major,
3. megaloblastic anemia
109
Sherocyte: Spherical RBC (membrane loss) associated with what?
2
1. Hereditary spherocytosis,
| 2. immune hemolytic anemia
110
Schistocytes “Helmet cells”: fragmented cells due traumatic membrane disruption are associated with what?
4
1. Microangiopathic hemolytic anemia (HUS/TTP, DIC, pre-eclampsia, HELLP, malignant HTN),
2. vasculitis,
3. glomerulonephritis,
4. prosthetic heart valve
111
Acanthocyte (spur cell): Distorted RBC with irregularly distributed thorn-like projections due to abnormal membrane lipids is associated with what?
3
1. Severe liver disease (spur cell anemia),
2. starvation/anorexia,
3. post-splenectomy
112
Howell-Jolly bodies: small nuclear remnant resembling a pyknotic nucleus are associated with what?
4
1. post splenectomy,
2. hyposplenism (sickle cell disease),
3. neonates,
4. megaloblastic anemia
113
Basophilic stippling: deep blue granulations indicating ribosome aggregation are assocaited with what?
5
1. thalassemia,
2. heavy metal poisoning,
3. megaloblastic anemia,
4. alcoholics,
5. hereditary
114
Rouleaux formation: Aggregates of RBC resembling stacks of coins due to increased plasma concentration of high molecular weight proteins are associated with what?
Most common cause-pregnancy due to fibrinogen increase, inflammatory conditions –polyclonal immunoglobulins, plasma cell dyscrasia – monoclonal paraproteinemia e.g. multiple myeloma
115
Echinocytes “Burr cells”: RBC with numerous regularly spaced, small spiny projections are associated with what?
6
1. Uremia,
2. HUS,
3. burns,
4. cardipulmonary bypass,
5. post-transfusion,
6. storage artifact.
116
Heinz bodies: denatured and precipitated Hgb are associated with what?
3
1. G6PD deficiency post exposure to oxidants,
2. thalassemia,
3. unstable Hgb
117
Sideroblasts: RBCs with Fe containing granules in the cytoplasm are associated with what?
4
1. hereditary,
2. idiopathic, drugs,
3. hypothyroidism,
4. sideroblastic anemia
118
Nucleus: Present in erythroblasts (immature RBCs) are associated with what?
3
1. Hyperplastic erythropoesis seen in hypoxia,
2. hemolytic anemia,
3. extramedullary hematopoiesis (in BM infiltration)
