L11: Nutritional Anaemias Flashcards
Define anaemia
→the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body’s physiologic needs
What is insufficient oxygen carrying capacity due to?
→reduced haemoglobin concentration as seen with insufficient RBC
How many chains are found in Hb?
→alpha=2
→beta=2
What are the basic requirements for normal erythropoeisis?
→Vitamin B12 & folic acid →Iron →vitamins →cytokines →healthy bone marrow environment
Why is VitB12 and folic acid needed for erythropoiesis?
→DNA synthesis
Why is iron needed for erythropoeisis?
→Hb synthesis
→Essential for O2 transport
→Most abundant trace element in body
What are the three mechanisms of action that leads to anaemia?
→hypoproliferation
Reticulocytopenic
→Ineffective Erythropoiesis
→Decreased Survival
Give three examples of microcytic anaemias
→Iron deficiency
→Thalassemia
→anaemia of chronic disease
What is thalassaemia due to?
→globin deficiency
Give examples of normocytic diseases
→anaemic chronic disease →aplastic anaemia →chronic renal failure →bone marrow infiltration →SCD
Give examples of macrocytic diseases
→b12 deficiency →folate deficiency →myelodysplasia →alcohol/drug induced →liver disease →myxoedema
What does reticulocyte count inform on?
→whether marrow can actually make cells
→adds further clue as to failure of production or increased losses
What is nutritional anaemia?
→Anaemia caused by lack of essential ingredients that the body acquires from food sources
What deficiencies are found in nutritional anaemias?
→Iron deficiency
→Vitamin B12 deficiency
→Folate deficiency
What are foods that are rich in iron?
→Meats
→seafood
→vegetables
→wheat
How does iron absorption differ between meat eaters and vegetarians?
→Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater.
How is excess iron dealt with?
→regulation is at absorption level, not excreted is an essential component of cytochromes, oxygen-binding molecules
Where is dietary iron absorbed?
→predominantly in the duodenum
How does iron circulate?
→bound to plasma transferrin and accumulate within cells in the form of ferritin
How is 2/3 of the iron in the body incorporated?
→incorporated into haemoglobin in developing erythroid precursors and mature red cells
Which other cells is iron found in?
→hepatocytes and reticuloendothelial macrophages
What do reticuloendothelial macrophages do?
→ingest senescent red cells,
→catabolise haemoglobin to scavenge iron,
→load the iron onto transferrin for reuse
How many states of iron are in the body?
→ferric states- 3+
→ferrous states- 2+
Where are ferrritin and haemosiderin found?
→liver
→spleen
→bone marrow
How is iron regulated?
→Regulated by GI mucosal cells and hepcidin
How is iron absorbed?
→Via ferroportin receptors on enterocytes
→Transferred into plasma and binds to transferrin
What affects absorption activity?
→GI acidity,
→state of iron storage levels
→bone marrow
What is hepcidin?
→iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron
What does hepcidin do to ferroportin?
→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
How is hepcidin feedback regulated?
→by iron concentrations in plasma
→the liver and by erythropoietic demand for iron.
What do transferrin bind to in the bone marrow?
→receptors on RBC precursors
What is the relationship between transferrin and Fe store levels?
→inversely proportional to Fe stores
What is an indirect measurement of transferrin in the lab?
→total iron binding capacity
Why is ferritin an unreliable measure?
→part of immune system and can be raised in immune response
What is TIBC levels like in iron deficiency anaemia?
→high
What studies are involved in iron deficiency investigations?
→FBC: Hb, MCV, MCH, Reticulocyte count
→Iron Studies: Ferritin, Transferrin Saturation
→blood film
Which test is most sensitive indicator of mild iron deficiency?
→serum ferritin
What is anisocytosis?
→variation of red cell size
What is the most common cause of IDA in adult men and postmenopausal women?
→Blood loss from the GI tract
What are the sigs for IDA?
→pallor of mucous membranes,
→Bounding pulse, systolic flow murmurs,
→Smooth tongue, koilonychias
What type of anaemia is consistent with B12 and folate deficiency?
→macrocytic anaemia
→Low Hb and high MCV with normal MCHC
What is the reticulocyte count like in megablastic macrocytic anaemia?
→low
What are the causes of megablastic macrocytic anaemia?
→Vitamin B12/Folic acid deficiency
→Drug-related eg methotrexate (interference with B12/FA metabolism)
What are the causes of nonmegaloblastic macrocytic anaemia?
→Alcoholism ++ →Hypothyroidism →Liver disease →Myelodysplastic syndromes →Reticulocytosis (haemolysis)
Where is B12 and folate absorbed?
→B12= ileum via IF
→folate=duodenum and jejunum
How long is the average body store for B12 and folate?
→B12=2-4 years
→folate=3-4 months
How much does cooking affect B12 and folate?
→10-30% loss for B12
→60-90% loss after cooking
What is another name for B12?
→cobalamin
Why is B12 and folic acid important?
→Both important for the final maturation of RBC and for synthesis of DNA
→Both needed for thymidine triphosphate synthesis
What are the characteristics of megaloblastic on peripheral smears?
→macroovalocytes and hypersegmented neutrophils
What are the causes of increased demand leading to folate deficiency?
→Infancy and growth spurts
→Haemolysis & rapid cell turnover: eg SCD
→Disseminated Cancer
→Urinary losses: eg heart failure
What are the causes of decreased absorption in folate deficiency?
→folate antagonists
→jejunal resection
→tropical sprue
What is B12 essential for?
→methylation in DNA and cell metabolism
→Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
How is IF made?
→Parietal Cells in stomach
What molecules transport B12 to tissues?
→Transcobalamin II and Transcobalamin I
What is pernicious anaemia?
→Lack of IF
Lack of b12 absorption
Autoimmune- IF antibodies
What are the causes of impaired absorption is B12 deficiency?
→pernicious anaemia
→Gastrectomy or ileal resection
→Zollinger-Ellison syndrome
→parasites
What are some congenital causes of B12 deficiency?
→IF
→cobalamin mutation
What are some haemotological consequences of B12 deficiencies?
→low ret count
→low/normal Hb
→raised LDH
What are the clinical consequences of B12 deficiency?
→Neurology: myelopathy, sensory changes, ataxia, spasticity (SACDC) →infertility →Brain: cognition, depression, psychosis →Tongue: glossitis, taste impairment →Blood: Pancytopenia
What are treatments for B12 and folate deficiency?
→Folic Acid – oral supplements
B12 – oral vs intramuscular treatment
