Iron, B12, Folate

Question 1

Iron

Answer 1

No metabolic pathway to get rid of iron
       Loss through bleeding, menstrual periods 
Essential element
  Males 10mg per day
  Females 18mg per day
  We absorb about 1mg per day (10%)

Question 2

Iron functions

Answer 2

Oxygen carriers
  hemoglobin
Oxygen storage
  Myoglobin
Energy production
  Cytochromes (oxidative phosphorylation)
  Krebs cycle enzymes
Other
  Liver detoxification

Question 3

Transferrin

Answer 3

Synthesised in the liver.
Each molecule can bind two Fe3+ molecules (oxidized)
Contains 95% of serum Fe.
Usually about 30% saturated with Fe.
Production decreased in iron overload.
Production increased in iron deficiency.
Measured in blood as a marker of iron status.

Question 4

Hepcidin

Answer 4

25 aa peptide
Antimicrobial activity
Hepatic bacteriocidal protein
Master iron regulatory hormone
Inactivates ferroportin
  Stops iron getting out of gut cells
  Iron lost in stool when gut cells shed
Leads to decreased gut iron absorption

Question 5

hematochromatosis

Answer 5

Too much iron

Sx. include: Fatigue, loss of libido, joint ache, skin bronzing, liver abnormalities, weakness…

Question 6

Vitamin B12 (Cobalamin) Overview

Answer 6

Normal functioning of the brain and nervous system

Formation of blood

Normally involved in the metabolism of every cell of the human body especially affecting DNA synthesis and regulation

Question 7

Vitamin B12 (Cobalamin) Key Roles

Answer 7

recycling of folates:
Folates support red blood cell production
Helps prevent homocysteine build up in blood
High levels leads to inflammation/coronary heart disease

methionine synthesis
Methionine is an essential amino acid
Comes from meat, fish and dairy products
Used in Europe to treat depression, liver disease, inflammation and certain muscle pains.

Question 8

Vitamin B12 RDA

Answer 8

Total amount of B-12 required per day is only about 5ug
Normal liver/tissue storage is about 1000 times the daily need
**Vitamin B12 deficiency and folate deficiency show the same symptoms.

Question 9

B12 absorption occurs in two phases:

Answer 9

The gastric phase
IF (Intrinsic factor) binds to B12

The intestinal phase
IF-B12 complex is absorbed in the ileum through specific llieal receptors.

Question 10

Vitamin B12 deficiency

Answer 10

Similar to Folate, but B12 has neuropathy

Supplement of folate alone aggravates the neuropathy:
B12 and Folate should be given together
Never give folate to an individual with megaloblastic anemia because it will mask B-12 deficiency and neurological degeneration will continue.

Question 11

Folate (Folic Acid)

Answer 11

Vitamin B9
Folate (the anion form of folic acid)
Need a good balance between folate & B12
Participates in a single carbon transfer (e.g., synthesis of choline, serine, glycine, methionine, nucleic acids)

Question 12

Folate deficiency

Answer 12

Hyperhomocysteiemia, a risk factor for cardiovascular diseases

Megaloblastic anemia (which results from a deficiency of vitamin B12 and folic acid)

Significant relationship btw folate and neural tube defects, cancer and cardiovascular disease led to FDA-mandated fortification of bread, cereals, pasta and other grain products

Question 13

Microcytes

Answer 13

Drastically smaller RBC (less than 7 microns) indicative of iron deficiency and defective Hgb synthesis

Associated conditions:
Microcytic anemia, IDA, thalassemia, sickle cell anemia, hemoglobinopathy

Question 14

Macrocytes

Answer 14

Larger (>8.5 microns in diameter) indicative of megaloblastic anemias and aplastic anemias

Associated conditions: Macrocytic anemia, Reticulocytosis, Liver disease, hemolytic anemia, recovery from acute hemorrhage, asplenia, aplastic anemia, myelodysplasia, endocrinopathies

Question 15

Polychromasia

Answer 15

Young RBC’s seen in severe anemia.

Question 16

Hypochromasia

Answer 16

Cells have decreased hgb content has increased central pallor indicative iron deficiency anemia.

Question 17

Target cells (codocytes)

Answer 17

bulls eye” on dried film

Associated condition: Liver disease, hemoglobin SC, thalassemia, Fe deficiency, asplenia

Question 18

Elliptocytes/ Ovalcytes

Answer 18

Oval shaped elongated RBCs

Associated condition: Hereditary elliptocytosis, megaloblastic anemia, myelofibrosis, iron deficiency, MDS

Question 19

Dacrocyte (tear drop cell)

Answer 19

Single pointed end, looks like a tear drop

Associated condition: Myelofibrosis, extramedullary hemopoiesis, thalassemia major, erythroleukemia, megaloblastic anemia

Question 20

Spherocyte

Answer 20

Spherical RBC (membrane loss)

Associated condition: Hereditary spherocytosis, immune hemolytic anemia, acute alcoholism, Hgb C disease, severe burn injury, hemolytic transfusion reactions, severe hypophosphatemia

Question 21

Schistocytes “Helmet cells”

Answer 21

fragmented cells due traumatic membrane disruption

Associated condition: Microangiopathic hemolytic anemia (HUS/TTP, DIC, pre-eclampsia, HELLP, malignant HTN), vasculitis, glomerulonephritis, prosthetic heart valve

Question 22

Acanthocyte (spur cell)

Answer 22

Distorted RBC with irregularly distributed thorn-like projections due to abnormal membrane lipids

Associated condition: Severe liver disease (spur cell anemia), starvation/anorexia, post-splenectomy, hepatic necrosis, pyruvate kinase deficiency, uremia.

Question 23

Howell-Jolly bodies

Answer 23

small nuclear remnant resembling a pyknotic nucleus

Associated condition: post splenectomy, hyposplenism (sickle cell disease), neonateds, megaloblastic anemia

Question 24

Basophilic stippling

Answer 24

deep blue granulations indicating ribosome aggregation

Associated condition: thalassemia, heavy metal poisoning, Arsenic poisoning, sideroblastic anemia, megaloblastic anemia, alcoholics,,hemolytic anemia, unstable Hgb, Pyridine 5’-nucleotidase deficiency (hereditary)

Question 25

Rouleaux formation

Answer 25

Aggregates of RBC resembling stacks of coins due to increased plasma concentration of high molecular weight proteins

Associated condition: Most common cause-pregnancy due to fibrinogen increase, inflammatory conditions –polyclonal immunoglobulins, plasma cell dyscrasia – monoclonal paraproteinemia e.g. multiple myeloma

Question 26

Echinocytes “Burr cells”

Answer 26

RBC with numerous regularly spaced, small spiny projections

Associated condition: Uremia, HUS, burns, cardipulmonary bypass, post-transfusion, storage artifact.

Question 27

Heinz bodies

Answer 27

denatured and precipitated Hgb

Associated condition: G6PD deficiency post exposure to oxidants (Oxidative Hemolytic Anemia), thalassemia, unstable Hgb

Question 28

Sideroblasts

Answer 28

RBCs with Fe containing granules in the cytoplasm
Associated condition: Nucleated RBCs, hereditary, idiopathic, drugs, hypothyroidism, sideroblastic anemia, Iron Laden mitochondria

Question 29

Nucleus/ Cabot’s Ring Bodies

Answer 29

Nuclear remnants - Present in erythroblasts (immature RBCs)

Associated condition: Lead toxicity, Pernicious anemia, Hemolytic anemia