The Nutritional Anaemias Flashcards
What is anaemia?
Anaemia is a condition where number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient for body’s physiological needs
What causes the oxygen insufficiency of anaemic RBCs ?
Insufficient oxygen carrying capacity is due to reduced haemoglobin concentration as seen with insufficient RBC
What is haemoglobin?
Iron containing oxygen transport metalloprotein
What is the consequence of decreased Hb in RBCs?
Within RBCs
Reduction in haemoglobin = anaemia (reduction in oxygen carrying capacity)
What do RBCs require in order to mature?
- Vitamin B12 & folic acid; DNA synthesis
- Iron; Haemoglobin synthesis
- Vitamins
- Cytokines (erythropoeitin)
- Healthy bone marrow environment
What mechanism failures cause anaemia to occur?
- Failure of Production: hypoproliferation,
Reticulocytopenic - Ineffective Erythropoiesis
- Decreased Survival: Blood loss, haemolysis,
reticulocytosis
What are the different types of low Hb anaemias?
- Microcytic
- Normocytic
- Macrocytic
Outline the microcytic low Hb anaemias
- iron deficiency (low heme)
- thalassaemia (globin deficiency
- anaemia of chronic disease
What are the normocytic low Hb anaemias?
- anaemia chronic disease
- aplastic anaemia
- chronic renal failure
- bone marrow infiltration
- sickle cell disease
What anaemias cause macrocytic low Hb levels?
- B12 / Folate deficiency
- myelodysplasia
- alcohol / drug induced
- liver disease
- myxoedema
Apart from Hb what other aspect of RBCs can we look at to diagnose anaemia type?
Reticulocyte count then adds further clue as to failure of production or increased losses
Find out if anaemia is acquired or hereditary
What are nutritional anaemias?
Anaemia caused by lack of essential ingredients that the body acquires from food sources
Lack of which essential sources can lead to nutritional anaemia?
Iron deficiency
Vitamin B12 deficiency
Folate deficiency
What is the significance of iron?
Essential for O2 transport, Most abundant trace element in body
What is the daily requirement of iron?
Daily requirement for iron for erythropoiesis varies depending on gender and physiological needs
Where is the majority of iron in the body acquired from?
Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood)
How does a vegetarian diet affect Iron levels?
Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater
How is iron requirement variable between genders?
Women require more iron due to menstruation and especially during pregnancy
Menopausal women require ~similar amounts as men
What is the role of iron in the body?
Iron is an essential component of cytochromes, oxygen-binding molecules (i.e., haemoglobin and myoglobin), and many enzymes.
Where is dietary iron absorbed?
Dietary iron is absorbed predominantly in the duodenum
How does iron travel through GI system to cells?
Fe3+ ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin
Stored iron can be mobilized for reuse
Outline the average amount of iron carried by an adult male
Adult men normally have 35 to 45 mg of iron per kilogram of body weight
Why do women have lower iron levels than men?
Premenopausal women have lower iron stores due to recurrent blood loss through menstruation
Where does majority of dietary iron end up in the body?
More than 2/3 of body’s iron content incorporated into Hb in developing erythroid precursors and mature red cells
Where is the iron (not used in Hb) found?
Most remaining body iron is found in hepatocytes and reticuloendothelial macrophages, which serve as storage deposits
What is the role of reticuloendothelial macrophages?
Reticuloendothelial macrophages
- ingest senescent red cells
- catabolise Hb to scavenge iron
- load iron onto transferrin for reuse
How is iron metabolism regulated?
Iron metabolism is unusual in that it is controlled by absorption rather than excretion.
How is iron ever lost?
Iron is only lost through blood loss or loss of cells as they slough
How much iron is lost on average?
Men and non-menstruating women lose about 1 mg of iron per day
Menstruating women lose from 0.6 to 2.5 percent more per day.
Describe the structure of Hb
Hb: 4 haem groups, 4 globin chains able to bind 4 O2
What are the different forms of iron in the body?
>1 stable form of iron: Ferric states (3+) and Ferrous states (2+)
How is iron stored in the body?
Remaining Fe kept as storage and transport proteins ferritin and hemosiderin
Found in cells of liver, spleen and bone marrow
Where is iron absorbed?
Duodenum & proximal jejunum
Via ferroportin receptors on enterocytes
Transferred into plasma and binds to transferrin
What cells regulate iron absorption
Regulated by GI mucosal cells and hepcidin
What determines the amount of iron absorbed?
Amount absorbed depends on type ingested
Heme, ferrous (red meat, > than non-heme, ferric forms Heme iron makes up 10-20% of dietary iron
What factors effect amount of iron absorbed?
Other foods, GI acidity, state of iron storage levels and bone marrow activity affect absorption
What is the role of Hepcidin?
Hepcidin, its receptor and iron channel ferroportin control dietary absorption, storage, and tissue distribution of iron
What is Hepcidin?
the iron-regulatory hormone
How does hepcidin decrease iron transfer to blood palsma?
Hepcidin causes ferroportin internalization and degradation
Which structures transfer iron to the blood plasma?
Iron transfer into blood plasma occurs from:
- the duodenum
- macrophages (involved in recycling senescent erythrocytes)
- iron-storing hepatocytes.
How is hepcidin activity mediated?
Feedback regulated by
- [iron] in plasma and liver
- erythropoietic iron demand
Where is iron transported and stored?
Iron transported from enterocytes and then either into plasma or if excess iron stored as ferritin
How is iron stored in plasma?
In plasma: attaches to transferrin and then transported to bone marrow binds to transferrin receptors on RBC precursors
How does ferrtin and transferrin levels change during iron deficiency?
A state of iron deficiency will see reduced ferritin stores and then increased transferrin
How does serum Fe levels change throughout the day?
Serum Fe fluctuates throughout the day depending on what you eat
What does a lab ferritin level study tell us?
Low ferritin levels show iron store levels and allow diagnoses of iron deficiency
What other factor may cause ferritin levels to increase
Ferritin also part of the immune system
Ferritin levels may increase due to infection and may not necessarily mean iron levels have also increased
Outline the lab results indicating iron deficiency anaemia
Low Ferritin
Low TF saturation
High TIBC
Low/Norm Serum Fe
What are the causes of Iron deficiency anaemia?
NOT ENOUGH IN
- Poor Diet
- Malabsorption
- Increased physiological needs
LOSING TOO MUCH
- Blood loss: menstruation, GI tract loss, parasites
Outline tests carried out to investigate IDA
FBC: Hb, MCV, MCH, Reticulocyte count
Iron Studies: Ferritin, Transferrin Saturation
Blood film
BMAT and Iron stores
Describe the type of anaemia seen in IDA
Iron deficiency anaemia is initially normocytic and normochromic
Describe the development of IDA
Before anaemia develops, iron deficiency occurs in several stages
Transferrin % saturation w/ Fe + free erythrocyte protoporphyrin values become abnormal after tissue stores are depleted of iron
Decreased {Hb] when iron is unavailable for haem synthesis
MCV and MCH aren’t abnormal for several months after tissue stores depleted of iron
What are the lab indicators of anaemia?
Serum ferritin = most sensitive laboratory indicators of mild iron deficiency
Stainable iron in tissue stores is equally sensitive, but not performed in clinical practice
Why may reticulocyte numbers be normal in IDA patients?
The reticulocyte count inappropriately normal, as would expect bone marrow to compensate for anaemia by producing more new red cells.
What is anisocytosis?
variation of the red cell size
What is hypochromia?
area of central pallor of red cells that is larger than normal, indicates a low MCHC
Outline the prevalence of IDA
World’s most common nutritional deficiency - 2% in adult men (≤ 69 years old) - 4% in adult men ≥ 70 years old* - 10% in Caucasian, non-Hispanic women - 19% in African-American women - Common cause of referral - Excessive menstrual losses 1st cause in premenopausal women
What is the most common cause of IDA in men and postmenopausal women?
Blood loss from the GI tract is the most common cause of IDA in adult men and postmenopausal women
Outline the signs and symptoms of IDA
Symptoms
fatigue, lethargy, and dizziness
Signs pallor of mucous membranes, Bounding pulse, systolic flow murmurs, Smooth tongue, koilonychias
Describe the lab findings seen in B12/folate deficient patients
Macrocytic Anaemia
Low Hb and high MCV with normal MCHC
What are the causes of macrocytic megaloblastic anaemia
Megaloblastic
- Low reticulocyte count
- Vitamin B12/Folic acid deficiency
- Drug-related (interference with B12/FA metabolism)
What are the causes of macrocytic non-megaloblastic anaemia?
Non-megaloblastic
- Alcoholism ++
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (haemolysis)
What is the significance of B12 and folate?
Both important for the final maturation of RBC and for synthesis of DNA
Both needed for thymidine triphosphate synthesis
What are the sources of B12 and folate?
B12: Animal and dairy produce
Folate: vegetables, liver
Describe the characteristics of a megaloblastic blood film
Seen in B12 and Folic Acid deficiency.
Characterized by macro-ovalocytes and hypersegmented neutrophils
Describe the blood film of Folate deficient patients
Megaloblastic anemia, with macroovalocytes and hypersegmented neutrophil
- Reticulocytes: 20
- Folate 0.9 (5-15)
- B12 163 (180 – 350)
What is the role of folate?
Folate required for DNA synthesis, specifically the nucleotide bases; adenine, guanine, thymidine synthesis
Describe the blood film of a myelodysplastic patient
Anaemia in myelodysplastic syndrome with
several macrocytes
How is folate acquired in to the body?
Folate comes from most foods with 60-90% lost in cooking
Where is folate absorbed?
Absorbed in Jejunum
Body has enough stores usually for 3-5 months
What is Vitamin B12?
Essential cofactor for methylation in DNA and cell metabolism
What is the role of B12?
Required for the intracellular conversion of 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
What substance is needed for B12 absorption?
Requires the presence of Intrinsic Factor for absorption in terminal ileum
Where is intrinsic factor (IF) produced?
IF made in Parietal Cells in stomach
Describe the transportation of vit. B12
Transcobalamin II and Transcobalamin I transport vitB12 to tissues
What are the different types of B12 Deficiency causes
- Impaired absorption
- decreased intake
- congenital
- increased requirement
- medication
What disorders cause impaired absorption of B12?
- pernicious anaemia
- gastrectomy / ileal resection
- zollinger-ellison syndrome
- parasites
What kind of diets decrease B12 intake?
malnutrition
vegan diet
Outline congenital causes of B12 deficiency
- IF receptor deficiency
- cobalamin mutation CG1 gene
What conditions cause patients to need an increased B12 requirement ?
- haemolysis
- HIV
- pregnancy
- Growth spurts
What medications cause B12 deficiency?
alcohol
NO
PPI, H2 antagonists
metformin
What are the haematological consequences of B12 deficiency?
High MCV
Low/Norm Hb
Low reticulocyte count
Describe a B12 deficient blood film
macrocytes, ovalocytes, hypersegmented neutrophils
Outline some of the clinical consequences of B12 deficiency
Brain: cognition, depression, psychosis Neurology: myelopathy, sensory changes, ataxia, spasticity (SACDC) Infertility Cardiac cardiomyopathy Tongue: glossitis, taste impairment Blood: Pancytopenia
What are the characteristics of pernicious anaemia?
Autoimmune disorder
Lack of IF
Lack of B12 absorption
Gastric Parietal cell antibodies
IF antibodies
What is the basis of nutritional anaemia treatments?
Treat the underlying cause
What are the treatments available for nutritional anaemic patients?
Iron – diet, oral, parenteral iron supplementation, stopping the bleeding
Folic Acid – oral supplements
B12 – oral vs intramuscular treatment
