Session 4- Introduction to anaemia & Vitamin B12 and folate metabolism Flashcards
define anaemia
a haemoglobin concentration lower than the normal range which varies
clinical signs of anaemia
glossitis, spoon shaped nails, angular chelitis
-Pallor • Tachycardia • Systolic flow murmur • Tachypnoea • Hypotension
symtoms of anaemia
Shortness of breath • Palpitations • Headaches • Claudication • Angina • Weakness & Lethargy • Confusion
key clinical point of anaemia
Anaemia in itself is not a diagnosis but a
manifestation of an underlying disease state and it
is important to establish the cause of the anaemia
specific signs associated with the cause of anaemia
Koilonychia
Glossitis
Angular stomatitis
Abnormal facial bone
development
Rare in recent times as
preventable with early diagnosis
Thalassaemia
koilonychia
(Spoon shaped nails)
Iron deficiency
glossitis
(inflammation & depapillation of tongue)
Vitamin B12 deficiency
angular stomatitis
(Inflammation of corners of the mouth)
Iron deficiency
why might anaemia develoop- bone marrow
Reduced or dysfunctional erythropoiesis Abnormal Haem synthesis Abnormal globin chain synthesis
why might anaemia develop- peripheral red blood cells
abnormal structure
mechanical damage
abnormal metabolism
removal- spleen
why might anaemia develop
increased removal by reticuloendothelial system
what is the role of erythropeitin in the hormonal control of erythropoiesis
when there is low blood oxygen pericytes in kidney sense hypoxia and produce erythropoietin
EPO travels in bloodstream and binds to receptors on erythblasts in bone marrow and stimulates red cell production
increased number of red cells in blood
high blood oxygen
negative feedback on pericytes
why might anaemia develop in reduced or dysfuntional erythpoiesis
Anaemia can result from marrow being
unable to respond to EPO
myelofibrosis
anaemia of chronic disease
myelodysplastic syndroms
myelofibrosis
If marrow is infiltrated by cancer cells
or fibrous tissue (myelofibrosis) the
number of normal haemopoietic cells is
reduced
anaemia of chronic disease
In Anaemia of chronic disease e.g. in
rheumatoid arthritis, iron is not made
available to marrow for rbc production
myelodysplastic syndrome
In rare forms of blood cancer called myelodysplastic syndromes abnormal clones of marrow stem cells limit the capacity to make both red and white blood cells
why might anaemia develop- defects in haemoglobin synthesis
Defects in the haem synthetic
pathway can lead to
Sideroblastic anaemia
Insufficient iron in diet can lead to iron deficiency anaemia (not enough iron to make Haem) Anaemia of chronic disease can result in a functional iron deficiency (sufficient iron in body but not made available for erythropoiesis
mutations in the genes encoding the globin chain proteins
• α Thalassaemia
• β Thalassaemia
• Sickle cell disease
why might anaemia develop- defects in red cell metabolism
G6DPH deficiency
pyruvate kinase deficiency
why might anaemia devlop- excessive bleeding
Chronic bleeding
• Heavy menstrual bleeding • Repeated nosebleeds • Haemorrhoids Occult gastrointestinal bleeding (blood lost in stool) • Ulcers (stomach or small intestine) • Diverticulosis • Polyps in large intestine • Intestinal cancer • Kidney or bladder tumours (blood lost in urine)
autoimmune haemolytic anaemia
autoantibodies bind to the red cell membrane
proteins causing them to be recognised by
macrophages in the spleen and destroyed
2 key features can help to work out the cause of an anaemia
- The rbc size – macrocytic, microcytic, normocytic (big, small, normal)
- The presence or absence of reticulocytosis (has the marrow responded normally?)
reticulocytes
• Immature red blood cells (i.e. those which have just
been released from the marrow into blood)
• No nucleus & eliminate remaining mitochondria
• Typically compose ~1% of all red blood cells and take
~ 1 day to mature into erythrocytes
macrocytic anaemia
FAT RBC
foetus- increased folate demand in late pregnancy
alcohol- toxicity towards bone marrow + secondary likely B12/Folate deficiency
hypoThyrodism- low thyroid hormones affect hormones involved in haemopoiesis
reticulocytes- secondary to blood loss, many reticulocytes are produced
B12/Folate- deficiency/pernicious- thymine deficiency- uracil used - constant DNA repaire - nucleus never matures, glossitis
Cirrhosis/ chronic liver disease- not fully confirmed yet, maybe excess cholesterol deposition
megaloblastoc anaemia
• Interference with DNA synthesis during erythropoiesis causes development of nucleus to be retarded in relation to maturation of cytoplasm • Cell division delayed and erythroblasts continue to grow to form megaloblasts which give rise to larger red cells