4. Nutritional Anaemias Flashcards
(34 cards)
1
Q
What is anaemia?
A
- Number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet body’s physiological needs; can also be less than normal quantity of haemoglobin in blood
- Insufficient oxygen carrying capacity is due to reduced haemoglobin concentration as seen with insufficient RBC
- Hb in g/L
2
Q
What is haemoglobin? and what is expected on the blood film?
A
- Haemoglobin – iron containing oxygen transport metalloprotein within RBCs
- Varying normal concentration according the age, menstrual cycle, gender, pregnancy.
- On a blood film, if the RBC has sufficient levels of Hb, there would be a clear ring of colour
3
Q
What is required for normal erythropoiesis?
A
• Maturation of red blood cells require:
- Vitamin B12 and folic acid for DNA synthesis
- Iron for Haemoglobin synthesis
• Also need other vitamins, cytokines (erythropoietin), healthy bone marrow environment
4
Q
What mechanisms cause anaemia?
A
1) Failure of production: hypoproliferation -> reticulocytopoenic (decreased number of reticulocytes)
2) Ineffective erythropoiesis: (red blood cell production)
3) Decreased survival:
- > blood loss, haemolysis, reticulocytosis (increased number of reticulocytes/immature RBCs)
5
Q
How is anaemia classified?
A
Microcytic, normocytic, macrocytic anaemia - MCV
6
Q
Expand on microcytic
A
- Iron deficiency (haeme deficiency)
- Thalassaemia (globin deficiency)
- Anaemia of chronic disease
7
Q
Expand on normocytic
A
- Anaemia chronic disease
- Aplastic anaemia
- Chronic renal failure
- Bone marrow infiltration
- Sickle cell disease
8
Q
Expand on macrocytic
A
- B12 and folate deficiency
- Myelodysplasia – deficiency in the bone marrow where it makes abnormal RBCs
- Alcohol induced
- Drug induced
- Liver disease
- Myxoedema
9
Q
What are the different measurements to allow anaemia classification?
A
- MCV (mean cell volume) – of RBC, part of complete blood count
- Reticulocyte count – caused by failure of production (reticulocytopoenic) or increased losses?
10
Q
What are the key players in nutritional anaemia?
A
- Iron deficiency
- vitamin B12 deficiency
- folate deficiency
11
Q
Expand on iron.
A
- Essential for O2 transport (haemoglobin synthesis)
- Daily requirement for iron for erythropoiesis varies depending on gender (little bit more in a menstruating women) and physiological needs, increases in pregnancy and lactation
- Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood). Non heme iron absorption is lower (applies to those with vegetarian diets, for whom iron requirement is approx.. 2-fold greater)
12
Q
What is the distribution of iron within adults body? - inc, regulation and transport/storage
A
- Dietary iron -> plasma transferrin, mainly absorbed in duodenum
- MAJORITY of iron is in circulating erythrocytes (also a lot utilised in bone marrow and muscle myoglobin), storage iron in liver
- Iron levels are REGULATED by hepcidin ~ tells your body how to regulate it at absorption level
• TRANSPORT:
- transferrin and lactoferin
•STORAGE ~ most in hepatocytes and reticuloendothelial macrophages.
- Ferritin = short-terM
- Haemosiderin = long-term
- (found in cells of liver, spleen and bone marrow)
13
Q
Describe iron metabolism.
A
- Iron metabolism controlled by absorption (rather than usual excretion); only lost through blood loss or loss of cells as they slough
- More than 1 stable form of iron: Ferric states (3+) and Ferrous states (+2); these are two different oxidation states
- Reticuloendothelial macrophages ingest senescent RBCs, catabolise Hb to scavenge iron and load the iron onto transferrin for reuse
14
Q
Describe iron absorption
A
- Regulated by GI mucosal cells and hepcidin
- Most absorption in duodenum and proximal jejunum
- Via FERROPORTIN receptors on enterocytes
- Amount absorbed depends on the type ingested ~ heme, ferrous iron-containing proteins GREATER absorption than non-heme, ferric forms which is bound to other substances
- Other factors that affect absorption: other foods, GI acidity, state of iron storage levels, bone marrow activity
15
Q
How is iron concentration regulated?
A
HEPCIDIN
- Inhibits iron transport by binding to iron export channel ferroportin located on the BASOLATERAL surface of enterocytes and membrane of reticuloendothelial cells (macrophages), and hepatocytes
- Hepcidin causes ferroportin internalisation and degradation (lysosomal) -> decreased iron transfer into the blood plasma, from macrophages involved in recycling senescent erythroyctes and from iron-storing hepatocytes
- Hepcidin is feedback-regulated by iron concentrations in plasma and the liver and by erythropoetic demand for iron.
16
Q
Describe iron transport and storage.
A
- From duodenum into mucosal cells ~ Iron transported from enterocytes and then either into plasma or if excess iron stored as ferritin
- Combine with apoferritin (unbound ferritin) -> ferritin
- Or cross to plasma where it binds to transferrin and enter cells via transferrin receptor (e.g. in erythroid precursors)
17
Q
How can you carry out iron deficiency investigations?
A
- Full blood count (red blood cells): Hb, MCV, MCH, reticulocytes and blood film
- Iron studies: ferritin, transferrin saturation, TIBC (total iron binding capacity)
- Other studies: BMAT, iron stores
18
Q
What are the different lab iron studies?
A
- SERUM Fe - Hugely variable during the day.
- BLOOD TEST: FERRITIN – measures amount of iron stored; primary storage protein, provides reserve, water soluble ~ high levels can indicate iron storage disorder,
- BLOOD TEST: TRANSFERRIN – made by liver, inversely proportional to Fe stores, vital for Fe transport,
- URINE TEST: HAEMOSIDERIN – water insoluble, Fe- protein complex/iron-storage complex in cells; haemodiserinuria (brown urine) is secondary to excess intravascular haemolysis
- BLOOD TEST: IRON BINDING CAPACITY – shows capacity to bind iron with transferrin (indirectly reflects transferrin levels)
- BLOOD TEST: TRANSFERRIN SATURATIONS – Ratio of serum iron and total iron binding capacity – revealing % of transferrin binding sites that have been occupied by iron
19
Q
What would you see in a state of iron deficiency?
A
- Reduced Hb levels
- Reduced MCV
- Reduced MCH
- Reduced serum Fe
- Reduced ferritin
- Increased TIBC (reflecting transferrin)
- Reduced transferrin saturation
- Reduced/absent bone marrow iron studies
20
Q
What are the causes of iron deficiency?
A
- Not enough: poor diet, malabsorption, increased physiological needs (e.g. pregnancy)
- Losing too much: blood loss, menstruation, GI tract loss, parasites
21
Q
Iron deficiency occurs in several stages before anaemia develops. What are they?
A
- Initially normocytic and normochromic
- Moderate: microcytic (low MCV), hypochromic (low MCHC), reticulocytopoenic?
- Serum ferritin most sensitive indicator for mild iron deficiency
- Percentage saturation of transferrin with iron and free erythrocyte protoporphyrin (high levels indicate disruption of heme production?) values do not become abnormal until tissue stores are depleted of iron
- Decrease in Hb concentration -> when iron unavailable for haem synthesis
- MCV and MCH do not become abnormal for several months after tissues stores are depleted of iron.
22
Q
What is the prevalence of iron deficiency?
A
- World’s most common nutritional deficiency
- Blood loss from GI tract – most common causes of IDA in adult men and postmenopausal women
- Excessive menstrual losses – 1st cause in premenopausal women
23
Q
What are the symptoms of iron deficiency?
A
- Symptoms: fatigue, lethargy, dizziness
- Signs: pallor of mucous membranes, bounding pulse, systolic flow murmurs, smooth tongue, koilonychias (‘spoon nails’)
24
Q
Expand on clinical results of vitamin B12 and folate deficiency.
A
- Both have very similar lab findings and clinical symptoms
- Can be found together or as isolated pathologies
- Cause of macrocytic anaemia – low Hb, high MCV, normal MCHC
25
Expand on folate
- Folate necessary for DNA Synthesis:
Adenosine, guanine and thymidine synthesis
- absorbed in the Jejunum and the body
26
Causes of folate deficiency
=> Increase demand - e.g. pregnancy/breast feeding, infancy and growth spurts, haemolysis and rapid cell turnover (e.g. SCD), disseminated cancer and urinary losses (e.g. heart failure)
=> Decreased intake - e.g. poor diet, elderly and chronic alcohol intake
=> Decreased absorption - e.g. medication (folate antagonists), coeliac, jejunal resection and tropical sprue
27
Expand on vitamin B12.
- 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
- Animal sources: Fish, meat, dairy
- 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
28
What are the causes of B12 deficiency?
=> Impaired absorption - e.g. pernicious anaemia, gastrectomy/ileal resection, Zollinger-Ellison syndrome and parasites
=> Decreased intake - e.g. malnutrition, vegan diet
=> Congenital causes - intrinsic factor receptor deficiency, Cobalamin mutation, C-G-1 gene
=> Increase requirements - e.g. Haemolysis, HIV, pregnancy, growth spurts
=> Medication - e.g. alcohol, NO, PPI H2 antagonists, metformin
29
What are haematological consequences?
- Normal/raised MCV ~ megaloblastc anaemia ineffective erythropoeisis
- Normal/low Hb
- Low reticulocyte count
- Raised LDH ~ intramedullary haemolysis
- BLOOD FILM: macrocytes, ovalocytes, hypersegmented neuts
- BMAT: hypercellular, megaloblastic, giant metamyelocytes ~ unusual to need
- Increased MMA ~ not standard lab test
30
Clinical consequences
- Brain: cognition, depression, psychosis
- Neurology: myelopathy, sensort changes, ataxia, spasticity (SACDC)
- Infertility
- Cardiac cardiomyopathy
- Tongue: glossitis, taste impairment
- Blood: Pancytopenia (reduction in the number of red blood cells, white blood cells and platelets)
31
What is pernicious anaemia?
- Autoimmune disorder
- Lack of IF -> lack of B12 absorption
- From gastric parietal cell autoantibodies or IF autoantibodies
32
Treatments for iron, folate/B12 deficiency:
* Treat the underlying cause
* Iron – diet, oral, parenteral iron supplementation, stopping the bleeding
* Folic acid – oral supplements
* B12 – oral vs intramuscular treatment
33
Macrocytic anaemia: causes
```
• MEGALOBLASTIC: low reticulocyte count
- Vitamin b12/folic acid deficiency
- Drug-related
- Any interference with B12/folic acid metabolism
• NONMEGALOBLASTIC:
- Alcoholism ++
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (haemolysis)
```
34
Megaloblastic 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.
