Anaemia Flashcards
What is shown by an increase in unconjugated bilirubin
prehepatic/hepatic jaundice
How does bilirubin become conjugated
Bilirubin in the blood is bound to albumin (unconjugated). It is converted to conjugated bilirubin when entering the liver
What are some of the complications associated with a higher bilirubin?
Jaundice, Obstructive gall stones
What is hereditary spherocytosis?
Inherited disruption of vertical linkages in RBC cell membrane (ankyrin), -> spherocytes
What blood cells would you see in a blood film of hereditary spherocytosis?
Spherocytes, Cells with no central pallor, Reticulocytes
Why would you see reticulocytes in a blood film?
Compensatory effect - as more blood cells get destroyed, early forms of rbcs (reticulocytes) are released from the bone marrow prematurely to do some of the oxygen delivering
seen as polychromatic (blue tinge) cells
What causes raised bilirubin
RBC breakdown
What is haemolysis
^ destruction of RBC
due to intrinsic RBC abnormality
due to extrinsic factors acting on RBC
What is haemolytic anaemia
Haemolysis -> red. Hb
How to treat haemolytic anaemia
Folic acid (aid rq for erythropoeisis)
Splenectomy (^RBC lifespan)
Presentation of px with conjugated bilirubin
Pigment gallstones
Obstructive jaundice - block common bile duct
Difference btw unconjugated and conjugated bilirubin
Unconjugated bilirubin:
insoluble in blood - bound to albumin
Pre-hepatic jaundice
Toxic (to the brain)
Cannot be excreted via urine
Conjugated bilirubin:
Water soluble
small amounts loosely bound to albumin
post-hepatic jaundice (issues w/ bile duct/gallbladder)
Relatively non-toxic
Excreted in urine -> dark
Mechanism of anaemia
PPLS
Production (red. RBC/Hb prod by the bone marrow)
Pooling (Splenomegaly)
Loss of blood from the body
Survival (haemolysis).
What is DAT and how does it work
Direct Antiglobulin test
In solution coloured rabbit AB to identify whether blood contains autoantibodies (binds autoAB)
What does AIHA stand for and what are its causes
Autoimmune Haemolytic anaemia
idiopathic, SLE, lymphoma
What lab evidence would point towards haemolysis
^ LDH (lactate dehydrogenase)
Unconjugated hyperbilirubinemia (show prehepatic issue)
red. haptoglobulins (breakdown free Hb in liver)
What is the bone marrows response to haemolysis
Reticulocytosis
What causes aq haemolytic anaemia (HA)
Defect in the RBC environment (plasma, vasculature)
Non-immune environmental factors leading to aq HA
Haemolytic uraemic syndrome - AKI
Malaria - microbe
Snake venom
drugs - oxidant damage
Immune mediated factors leading to aq HA
Autoimmune
Alloimmune (post transfusion)
How can you differentiate between AIHA and hereditary spherocytosis?
DAT test - positive in AIHA
What inherited defects can affect RBC
Hereditary spherocytosis - membrane
Sickle cell anaemia - Hb
G6PD deficiency - Pentose shunt dysfunction
What is the purpose of the HMP Shunt?
Forms Glutathione and protects RBC from oxidant damage
What enzyme is critical in the HMP shunt that if deficient can lead to haemolytic anaemia?
G6PD
What can you see in a blood film for someone with G6PD deficiency?
Evidence of oxidant damage:
Bite cells w/ no central pallor
Heinz bodies - denatured Hb
Ghost cells
What does the presence of ghost cells show?
Intravascular Haemolysis
What advice would you give patients with G6PD deficiency?
Avoid oxidant drugs, broad beans, naphthalene (in cigarette smoke), protect against infection
Two types of HA
Inherited HA - abnormal membrane/Hb/enzymes
Acquired HA - extrinsic factors: microbes/chemicals/drugs
Where are the two locations that haemolysis can occur?
Intravascular - within blood vessels (acute damage to RBC)
Extravascular - in spleen or liver (due to removal)
What evidence would point towards HA
Morphologically abnormal RBC
^ RBC breakdown - ^bilirubin/red. haptoglobin
^ Bone marrow activity - ^MCV due to reticulocytes
Blood film abnormalities with iron deficiency anaemia
Microcytic (red. MCV)
Hypochromic (red. MCHC)
low ferritin/iron
Clinical signs of iron deficiency anaemia
Koilonychia - bent nails
Glossitis - inflammation of the tongue
Angular stomatitis - inflamed corners of the mouth
Causes of iron deficiency
^ loss - menstrual, GI
insufficient iron - dietary, malabsoption (coeliac)
^ iron rq - pregnancy
What conditions cause microcytic anaemia
Haem Synthesis Defect (iron deficiency, chronic disease)
Globin Synthesis Defect (alpha and beta thalassaemia)
What conditions lead to macrocytic anaemia?
B12 and folate deficiency
Liver disease
Drugs affecting DNA synthesis
What cells would be macrocytic and polychromatic?
Reticulocytes
What conditions lead to normocytic anaemia?
Recent blood loss - GI haemorrhage
Bone marrow failure (leukaemia/chemo),
Splenic Sequestration - hypersplenism
What are the symptoms of iron deficiency anaemia?
Tiredness, lethargy, breathlessness at rest, peripheral oedema
What is ferritin?
Stores of iron in the body
What is transferrin?
plasma transport protein
What is hepcidin?
Protein that inhibits Fe absorption/transport from the gut
released in response to xs ferritin
suppressed by EPO
What questions would you ask someone with iron deficiency anaemia?
Diet (vegan), Gastrointestinal Symptoms (bowels, indigestion, dysphagia), Menstrual History, Weight Loss, Medication (NSAIDs)
How do you treat iron deficiency anaemia?
Iron Replacement Therapy (Ferrous Sulphate)
What is shown in the blood film with high ESR
Rouleaux - stacks of RBC (looks like coins)
When plasma protein conc is high
What are some causes of anaemia of chronic disease?
Infections - TB, HIV
Rheumatoid/ autoimmune
Malignancy
How does chronic disease lead to anaemia?
Inflammatory responses ^ hepcidin production whilst also red. transferrin production
-> less Fe abs from gut / high ferritin
What are the key differences in ferritin/transferrin/transferrin saturation between iron deficiency anaemia and anaemia of chronic disease?
IRON - low ferritin (high in chronic) / high transferrin (low in chronic) / low transferrin saturation (normal in chronic)
What is pernicious anaemia?
Anaemia from deficiency of vitamin B12
What is poikilocytosis?
Variation in RBC shape
What does the term megaloblastic anaemia refer to?
Macrocytic anaemia caused by B12 or folate deficiency
What is a megaloblast and what are the features of it?
Abnormal erythroblast in the bone marrow - macrocytic, asynchronous nucleocytoplasmic maturation. It is NOT a reticulocyte
nucleus hypersegmentation
What are B12/folic acid rq for
Dna synthesis
What are some causes of B12 deficiency?
Dietary, Gastric (gastrectomy, autoimmune), Bowel (Crohn’s)
How would you treat each cause of b12 deficiency?
Dietary - oral supplements,
Gastric & Bowel - IM Hydroxocobalamin Injection
What are some causes of folate deficiency?
Red. Availability (diet, malabsorption - coeliac)
^ Demand (pregnancy, haemolysis)
How would you treat these causes of folate deficiency?
Oral supplements
Neurological disorders associated with B12/folate deficiency
Vit B12- Dementia, spinal cord degeneration
Folate - developmental neural tube defects
How does the body absorb B12
Cleared from food using HCL forms B12-IF (parietal cells)
B12-IF absorbed into ileum where it binds receptors
How does the body absorb folic acid
Absorbed into the duo/jej of the SI
