macrocytic and haemolytic anaemia Flashcards
is vitamin b12 soluble?
yes
what are symptoms of mild b12 deficiency?
fatigue, lethargy, depression, poor memory, breathlessness, headaches, pallor – esp in elderly people
what does prolonged vitamin b12 deficiency cause?
severe and irreversible nervous system damage
why is vitamin b12 deficiency common in alcoholics?
they get their calories from alcohol not food
what can cause megaloblastic macrocytic anaemia?
B12/B9 deficiency which causes inhibition of DNA synthesis during RBC production
what clinical test shows B12 deficiency?
increased serum methylmalonic acid (MMA)
why is testing MMA levels not a foolproof way of testing for B12 deficiency?
because not everyone who has increased MMA has a B12 deficiency
what are the uses of B12?
- myelin synthesis in the nervous system
- DNA synthesis - needed in cell metabolism esp RBCs
what is methionine synthase?
an enzyme which uses B12 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine
what is THF needed for?
DNA synthesis
how can you get THF?
from folate in the diet
how does taking folate supplements help in B12 deficiency?
fixes the lack of DNA synthesis but won’t fix the reduced myelin synthesis
is folate water soluble?
yes
what foods are rich in vitamin b12?
meat, eggs, cheese, animal protein
can vitamin b12 be destroyed by cooking?
no
what foods are rich in folate?
liver, greens, yeast
can folate be destroyed by cooking?
yes apart from brief cooking e.g. stir frying
why doesn’t a b12 deficiency show signs and symptoms immediately?
because the body stores b12 efficiently so temporary loss of B12 doesnt result in immediate symptoms
how does b12/folate deficiency result in anaemia?
reduced DNA synthesis –> cells fail to divide –> overly large RBCs –> increased rate of destruction of RBCs –> signs and symptoms of anaemia
where and how is folate absorbed?
duodenum and jejenum
how is b12 absorbed?
- released from food protein by stomach acid
- binds to IF from parietal cells of gastric mucosa and gets absorbed by receptors of ileum epithelial
where are parietal cells found?
gastric mucosa
what cells absorb b12?
ileum epithelial cells
what causes pernicious anaemia characterised by b12 deficiency?
caused by the absence/reduction of intrinsic factor (may be due to autoimmune disease)
what type of drug is omeprazole?
proton pump inhibitor
how can PPIs cause anaemia?
PPIs reduces the amount of acid in the stomach
impacts b12 and iron absorption
leads to anaemia
why do parietal cells release HCl in vesicles?
pass through the bicarbonate barrier lining the stomach then burst when they reach inside
what separates the ileum and the cecum?
the ileocecal valve at the ileocecal junction
what is the risk of a resection of the bowel?
risk of anaemia
what does the blood count of someone with b12 or folate deficiency look like?
decreased Hb, increased MCV (>120), decreased WBC and platelets
what does the blood film or someone with b12/folate deficiency look like?
oval macrocytes and hypersegmented neutrophils (more than 6 lobes)
what does the biochemistry of someone with b12/folate deficiency look like?
increased lactase dehydrogenase (LDH), increased bilirubin
why do people with b12/folate deficiency have increased LDH?
RBCs don’t have mitochondria, so they use LDH in glycolysis to turn pyruvate into lactate and vice versa
if RBCs burst open in anaemia then they release LDH –> high levels of LDH in anaemia
why might people with b12/folate deficiency have jaundice?
its removed from old senescent cells by splenic macrophages
increased haemolysis = increased bilirubin = jaundice
what are the main causes of b12 deficiency?
nutritional - poor diet e.g. vegans
malabsorption - pernicious anaemia
gastric - surgical gastrectomy
intestinal - ileal disease e.g. crohn’s
what is crohn’s disease?
IBD that can affect any part of the GI tract
cause unknown
causes body’s immune system to attacj the GI tract possibly directed at microbial antigens
what is pernicious anaemia?
autoimmune disorder
who is more at risk of pernicious anaemia?
females
associated with fair hair, blue eyes and blood group A
what causes pernicious anaemia?
autoantibody against parietal cells and IF
what problems can pernicious anaemia cause?
gastric atrophy
decreased acid
decreased IF secretion
B12 deficiency
which part of the body does autoimmune gastritis affect?
the parietal cells of the fundus but not the antrum
why does pernicious anaemia lead to iron deficiency and B12 deficiency?
because parietal cells produce acid (iron absorption) and intrinsic factor (B12 absorption)
what are the clinical features of pernicious anaemia?
insidious (gradual onset but fatal if untreated
anaemia
glossitis
mild jaundice
Neurological symptoms; peripheral neuropathy, damage to sensory and motor tracts, dementia, optic atrophy
what is the treatment of pernicious anaemia?
intramuscular B12 every 3 months for life
what do lab investigations show in someone with pernicious anaemia?
macrocytic anaemia
hypersegmented neutrophils
decreased serum B12
what are the causes of folate deficiency?
- Nutritional – old age, poverty, alcoholism
- Malabsorption – Coeliac, Crohn’s
- Excess utilisation – pregnancy, lactation
- Others – anticonvulsants
what are the clinical features of folate deficiency?
same as for pernicious anaemia but without neurological symptoms:
insidious (gradual onset but fatal if untreated
anaemia
glossitis
mild jaundice
what is the treatment for folate deficiency?
oral folic acid
what causes haemolytic anaemia?
shortened RBC survival
what is a sign of haemolytic anaemia?
jaundice without itching
what can long standing haemolysis cause?
gall stones which can obstruct the common bile duct
how does haemolytic anaemia present?
pallor, signs/symptoms of anaemia, jaundice, gallstones and splenomegaly
what are the normal levels of bilirubin in the body?
normally less than 17 micromoles/litre
what bilirubin levels cause jaundice?
Levels of over 34-51 cause jaundice
what are the three sites where pathology may be present in haemolytic anaemia?
- Membrane – hereditary spherocytosis (where immature RBCs don’t shrink down to adult size), oxidising agents, antibodies against RBC membrane (autoantibodies, alloantibodies)
- Haemoglobin - Abnormal structure (sickle cell disease); Imbalance in α:β synth (thalassaemia)
- Enzymes - Glucose-6-phosphate dehydrogenase def.
what do the lab investigations show in haemolytic anaemia?
- Red cell breakdown; increased serum unconjugated bilirubin, urinary urobilinogen, lactate dehydrogenase
- Increased RBC production; increased reticulocytes in blood and RBCs in marrow
what causes hereditary sphreocytosis?
Caused by a defect in proteins of RBC cytoskeleton bc of this the RBC contracts to its most surface-tension efficient and least flexible configuration (a sphere)
why is it bad that spherocytes are v fragile?
prone to physical degradation (e.g. when passing through capillaries)
what are the clinical features of hereditary spherocytosis?
autosomal dominant, chronic haemolytic anaemia, spherocytes visible in peripheral blood film, decreased Hb, increased LDH, increased unconjugated serum bilirubin
what is the function of glucose-6-phosphate dehydrogenase?
prevents/reverses the oxidation of Hb, membrane etc; prolongs the lifetime of RBCs
where is G6PD deficiency common?
Tropical Africa, Middle East, subtropical Asia, Mediterranean
when do G6PD carriers show symptoms?
when RBCs are exposed to certain triggers. can be of 3 main types;
o Foods – e.g. fava beans
o Bacterial or viral infection
o Drugs e.g. dapsone, cotrimoxazole, primaquine
how does autoimmune haemolytic anaemia work?
- IgG antibodies in the blood react with RBC membrane proteins
- IgG antibody attaches to RBC and labels for destruction
- Labelled RBCs then removed by spleen (extravascular haemolysis)
what is the coombs test?
a test for autoimmune haemolytic anaemia
how do you do the coombs test?
- take a blood sample from the patient - antibodies are shown attached to antigens on the RBC surface
- RBCs are washed and incubated with antihuman antibodies
- RBCs agglutinate; antihuman antibodies form links between RBCs by binding to the human antibodies on the RBCs
