The nutritional anaemia Flashcards
What condition is anaemia?
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 physiological needs
What is insufficient oxygen carrying capacity due to?
Insufficient oxygen carrying capacity is due to reduced haemoglobin concentration as seen with insufficient RBCs
What is Haemoglobin?
An Iron containing oxygen transport metalloprotein
What does normal erythropoiesis involve?
- Maturation of RBCs
- DNA synthesis
- Hb synthesis
What does maturation of RBC’s require?
Maturation of RBCs require:
- Vitamins
- Cytokines (erythropoietin)
- Healthy bone marrow environment
What does DNA synthesis require in erythropoiesis?
- Vitamin B12
- Folic Acid
What does Hb synthesis produce?
Iron
What are the mechanism of action for anaemia?
Failure of production: -hypoproliferation reticulocytopenic
- Ineffective erythropoiesis
- Decreased survival: blood loss, haemolysis, reticulocytosis
What is anaemia caused by a lack of?
Anaemia caused by lack of essential ingredients that the body acquires from food sources
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
What is Iron essential for?
Essential for O2 transport
What does recommended iron intake assume?
Recommended intake assumes 75% of iron is from haem iron sources (meats, seafood)
What is Iron an essentia component of?
Iron is an essential component of cytochromes, oxygen-binding molecules (i.e., haemoglobin and myoglobin), and many enzymes
Where is dietary iron absorbed predominantly?
Dietary iron is absorbed predominantly in the duodenum
What are Fe3+ ions bound to and what form do they accumulate in the cell in?
Fe3+ ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin
How much Iron do men have?
Adult men normally have 35 to 45 mg of iron per kilogram of body weight
Why do postmenopausal women have lower iron stores?
Premenopausal women have lower iron stores as a result of their recurrent blood loss through menstruation
What is more than 2/3 of the body’s iron content incorporated into?
More than two thirds of the body’s iron content is incorporated into haemoglobin in developing erythroid precursors and mature red cells
Where is 1/3 of the body iron content found?
Most of the remaining body iron is found in hepatocytes and reticuloendothelial macrophages, which serve as storage deposits
What do reticuloendothelial macrophages do and for what?
Reticuloendothelial macrophages ingest senescent red cells, catabolise haemoglobin to scavenge iron, and load the iron onto transferrin for reuse
How is Iron metabolism controlled?
Iron metabolism is unusual in that it is controlled by absorption rather than excretion
What is iron absorption regulated by?
Regulated by GI mucosal cells and hepcidin
- Duodenum & proximal jejunum
- Via ferroportin receptors on enterocytes
- Transferred into plasma and binds to transferrin
What is the iron regulatory hormone and and its receptor and what do they control?
iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage and tissue distribution of iron
What does Hepcidin cause and decrease?
Hepcidin causes ferroportin internalization and degradation
-Decreases iron transfer into blood plasma from the duodenum from macrophages involved in recycling senescent erythrocytes and from iron-storing hepatocytes
How is hepcidin regulated?
Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron
Where is iron transported from and to where and what happens if there’s excess iron?
Iron transported from enterocytes and then either into plasma or if excess iron stored as ferritin
Iron deficiency causes?
Not enough in: -Poor diet -Malabsorption -Increased physiological needs Losing too much: -Blood loss -Menstruation -GI tract loss -Parasites
What are the stages in development of iron deficiency anaemia?
- Before anaemia develops, iron deficiency occurs in several stages
- Serum ferritin is the most sensitive lab 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
- The reticulocyte count is inappropriately normal, since we would expect the bone marrow to compensate the anaemia by producing more new red cells
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
What is the cause of IDA in premenopausal women?
Excessive menstrual losses
What are the symptoms of anaemia?
- Fatigue
- Lethargy
- Dizziness
- Signs
- -Pallor of mucous membranes
- -Bounding pulse,
- -Systolic flow murmurs,
- -Smooth tongue, koilonychias
What can B12 and folate deficiency be found together as?
Can be found together of as isolated pathologies
What type of anaemia does B12 and folate deficiency cause?
Macrocytic anaemia
What are the symptoms of macrocytic anaemia?
- Low Hb
- High MCV
- Normal MCHC
What is megaloblastic macrocytic anaemia caused by?
Megaloblastic: low reticulocyte count
- Vitamin B12/Folic acid deficiency
- Drug-related
- (interference with B12/FA metabolism)
What is non-megaloblastic macrocytic anaemia caused by?
Nonmegaloblastic
- Alcoholism ++
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (haemolysis)
What is macrocyctic anaemia caused by?
- Vitamin B12 = cobalamin
- Folic acid
Why are both vitamin B12 and folic acid important?
- Both important for the final maturation of RBC and for synthesis of DNA
- Both needed for thymidine triphosphate synthesis
MEGALLOBLASTIC vs. NON MEGALOBLASTIC
- 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 is folate necessary for?
Folate necessary for DNA Synthesis: Adenosine, guanine and thymidine synthesis
What are the causes of folate deficiency?
- Increased demand like pregnancy
- Decreased intake from diet
- Decreased absorption due to medication
What is vitamin B an essential co factor for?
Essential co-factor for methylation in DNA and cell metabolism
Why is the intracellular conversion to 2 active coenzymes necessary?
Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
What does vitamin B12 require in order to be absorbed and where?
Requires the presence of Intrinsic Factor for absoprtion in terminal ileum
Where is intrinsic factor made?
IF made in Parietal Cells in stomach
What transports vitamin B12 to tissues?
Transcobalamin II and Transcobalamin I transport vitB12 to tissues
What are the clinical consequences of anaemia?
Brain: -Cognition -Depression -Psychosis Neurology: -Myelopathy -Sensory changes -Ataxua -Spasticity (SACDC) Infertility Cardiac cardiomyopathy Tongue: glossitis, taste impairment Blood: Pancytopenia
What is pernicious anaemia?
Autoimmune disorder
What is pernicious anaemia due to a lack of?
Lack of IF Lack of: -B12 absorption -Gastric Parietal cell antibodies -IF antibodies
What are the treatments for anaemia?
- Iron – diet, oral, parenteral iron supplementatin, stopping the bleeding
- Folic Acid – oral supplements
- B12 – oral vs intramuscular treatment
