Nutritional anaemia Flashcards
What is anaemia? (3)
- Anaemia is a condition in which the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body’s physiologic needs
- Insufficient oxygen carrying capacity is due to reduced haemoglobin concentration as seen with insufficient RBC
- Anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of haemoglobin in the blood
What is Hb?
- Iron containing oxygen transport metalloprotein
* Within RBCs
Can we use Hb levels to diagnose anaemia?
Yes
What does maturation of RBCs require?
• Maturation of red blood cells require
o Vitamin B12 & folic acid; DNA synthesis
o Iron; Haemoglobin synthesis
What are vitamins needed for?
o Cytokines (erythropoeitin) o Healthy bone marrow environment
What are the mechansism of action of anaemia?
• Failure of Production: hypoproliferation (bone marrow can make RBC but doesn’t have right ingredients)
o Reticulocytopenic
• Ineffective Erythropoiesis (cannot make it properly)
• Decreased Survival
o Blood loss, haemolysis, reticulocytosis
Give types of nutrional anaemia
o Iron deficiency
o Vitamin B12 deficiency
o Folate deficiency
What is the function of iron?
What’s our daily requirement and why do women need more?
- Essential for O2 transport
- Most abundant trace element in body
- Daily requirement for iron for erythropoeisis varies depending on gender and physiolgical needs
- Women need more iron due to blood loss from menstruation
What are the daily iron requirements?
- Daily dietary iron requirements differ at various stages of development, between men and women, and between pregnant and nonpregnant women.
- The data reported in this table assume an average dietary iron absorption of 10%.
- Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood). Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater.
How is iron distributed in the body?
- Iron is an essential component of cytochromes, oxygen-binding molecules (i.e., haemoglobin and myoglobin), and many enzymes.
- Dietary iron is absorbed predominantly in the duodenum.
- Fe+++ ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin. Stored iron can be mobilized for reuse.
- Adult men normally have 35 to 45 mg of iron per kilogram of body weight. Premenopausal women have lower iron stores as a result of their recurrent blood loss through menstruation.
- More than two thirds of the body’s iron content is incorporated into haemoglobin in developing erythroid precursors and mature red cells.
- Most of the remaining body iron is found in hepatocytes and reticuloendothelial macrophages, which serve as storage deposits.
- Reticuloendothelial macrophages ingest senescent red cells, catabolise haemoglobin to scavenge iron, and load the iron onto transferrin for reuse.
- Iron metabolism is unusual in that it is controlled by absorption rather than excretion. Iron is only lost through blood loss or loss of cells as they slough.
- Men and nonmenstruating women lose about 1 mg of iron per day. Menstruating women lose from 0.6 to 2.5 percent more per day.
- An average 60-kg woman might lose an extra 10 mg of iron per menstruation cycle, but the loss could be more than 42 mg per cycle depending on how heavily she menstruates.
- Average values in a 70-kg man. Values in women are lower
- Only lose iron from blood loss- very little excreted
What are the forms of stable iron?
What is it used for?
• >1 stable form of iron:
• Ferric states (3+) and Ferrous states (2+)
• Most iron is in body as circulating Hb
o Hb: 4 haem groups, 4 globin chains able to bind 4 O2
• Remainder as storage and transport proteins
• ferritin and haemosiderin
• Found in cells of liver, spleen and bone marrow
What absorbs iron?
What transports it into the blood?
- Regulated by GI mucosal cells and hepcidin
- Duodenum & proximal jejunum
- Via ferroportin receptors on enterocytes
- Transferred into plasma and binds to transferrin
- Amount absorbed depends on type ingested
- Heme, ferrous (red meat, > than non-heme, ferric forms Heme iron makes up 10-20% of dietary iron
- Other foods, GI acidity, state of iron storage levels and bone marrow activity affect absorption
How is iron-regulated by hepcidin?
How is hepacin regulated?
- the iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron…
- Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes.
- Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron.
How is iron transported?
How is iron deff identified
- Iron transported from enterocytes and then either into plasma or if excess iron stored as ferritin
- In plasma: attaches to transferrin
- and then transported to bone marrow binds to transferrin receptors on RBC precursors
- A state of iron deficiency will see reduced ferritin stores and then increased transferrin
Read over Laboratory iron studies
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What are the causes of ID?
NOT ENOUGH IN
• Poor Diet
• Malabsorption
• Increased physiological needs
LOSING TOO MUCH
• Blood loss
• menstruation, GI tract loss, paraistes
How can we investigate ID?
- FBC: Hb, MCV, MCH, Reticulocyte count
- Iron Studies: Ferritin, Transferrin Saturation
- Blood film
- ?BMAT and Iron stores
Describe the initial stages of ID?
- As you start to run out or iron stores ferritin respond very quickly
- Before anaemia develops, iron deficiency occurs in several stages.
- Serum ferritin is the most sensitive laboratory indicators of mild iron deficiency. Stainable iron in tissue stores is equally sensitive, but is not performed in clinical practice.
- The percentage saturation of transferrin with iron and free erythrocyte protoporphyrin values do not become abnormal until tissue stores are depleted of iron.
- A decrease in the haemoglobin concentration occurs when iron is unavailable for haem synthesis.
- MCV and MCH do not become abnormal for several months after tissue stores are depleted of iron.
What are the symptoms and signs of anaemia?
Symptoms • fatigue, lethargy, and dizziness Signs • pallor of mucous membranes, • Bounding pulse, • systolic flow murmurs, • Smooth tongue, koilonychias
Describe B12 and folate deficiency
- Both have very similar laboratory finding and clinical symptoms
- Can be found together or as isolated
- pathologies
- Macrocytic Anaemia
- Low Hb and high MCV with normal MCHC
What causes macrocytic anaemia?
- Megaloblastic : Low reticulocyte count
- Vitamin B12/Folic acid deficiency
- Drug-related
- (interference with B12/FA metabolism)
Define Nonmegaloblastic
What is folic acid needed for?
Anaemia causes by:
- Alcoholism ++
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (haemolysis)
- Vitamin B12 = cobalamin
- Folic acid
- Both important for the final maturation of RBC and for synthesis of DNA
- Both needed for thymidine triphosphate synthesis
Describe the differences in a blood film between megablastic and nonmegablastic anaemia
- Megaloblastic changes of blood cells are seen in B12 and Folic Acid deficiency
- They are characterized on the peripheral smear by macroovalocytes and hypersegmented neutrophils.
What are the causes of megablastic and nonmegablastic?
Diagnosis: Folate Deficiency
• Reticulocytes: 20
• Folate 0.9 (5-15)
• B12 163 (180 – 350)
• Folate necessary for DNA Synthesis:
• Adenosine, guanine and thymidine synthesis
• Folate comes from most foods with 60-90% lost in cooking. It is absorbed in the Jejunum and the body has enough stores usually for 3-5 months
What are the causes of Causes of Folate Deficiency?
On table
What is VB12 needed for?
- Essential co-factor for methylation in DNA and cell metabolism
- Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
- Foods containing vit B12:
- Animal sources: Fish, meat, dairy
- UK intake recommendations are 1.5mcg/day
- EU: 1mcg/day and USA: 2.4mcg/day
- average western intake 5-30mcg/day
- Body (liver) storage: 1-5mg so many years for deficiency
- Requires the presence of Intrinsic Factor for absoprtion in terminal ileum
- IF made in Parietal Cells in stomach
- Transcobalamin II and Transcobalamin I transport vitB12 to tissues
Give some causes of causes of B12 Deficiency
On table
What are the clinical and haematological consequences of VB12 deficiency?
Clinical consequences
• Brain: cognition, depression, psychosis
• Neurology: myelopathy, sensory changes, ataxia, spasticity (SACDC)
• Infertility
• Cardiac cardiomyopathy
• Tongue: glossitis, taste impairment
• Blood: Pancytopenia
What is Pernicious Anaemia and the treatments available?
- Autoimmune disorder
- Lack of IF
- Lack of
- B12 absorption
- Gastric Parietal cell antibodies
- IF antibodies
Treatments • Treat the underlying cause **** • Iron – diet, oral, parenteral iron supplementatin, stopping the bleeding • Folic Acid – oral supplements • B12 – oral vs intramuscular treatment
Look at summary table
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