Tales from haem clinic: RBC Flashcards
What is dietary source of iron?
red meat, green leafy vegetables, pulses
What is a dietary source of vitamin B12?
meat, fish, eggs, milk, cheese
What is a dietary source of folate?
green leafy vegetables, whole grain cereal, yeast, fruit, some other veggies
What is hepcidin?
Key regulator of the entry of iron into the circulation of mammals
What is ferroportin?
Transmembrane protein that transports iron from inside of a cell to outside
What does it mean by efflux?
flowing out of a substance
What is an enterocyte?
Highly specialised cell of the duodenal epithelium that coordinates iron uptake and transport in the body
What is erythropoiesis?
Producing RBC
What are the processes that regulate absorption of iron?
Hepcidin works by binding to ferroportin and inducing its internalisation
- thus preventing the efflux of iron from the duodenal enterocyte
The iron is then lost when the enterocyte dies and is shed into the gut lumen
When iron stores (ferritin) are full, there is upregulation of hepcidin expression and iron absorption is limited
- whereas a requirement for increased erythropoiesis leads to a reduction in hepcidin and iron absorption is increased
What are 3 mechanisms that can result in anaemia? (and a cause for it)
1) reduced production of RBC by bone marrow
- e.g., by deficiency of iron, B12, or folate, leukaemia
2) loss of blood from the body
- e.g. gastrointestinal bleeding, heavy menstrual bleeding
3) reduced survival of RBC in the circulation (haemolysis)
- e.g., sickle cell disease, G6PD deficiency, hereditary spherocytosis
2&3 can be written together as excess loss/ destruction
What is WBC and what are its units?
white blood cell count in a given volume of blood (x10^9/L)
What is Hb and what are its units?
haemoglobin concentration (g/L)
What is RBC and what are its units?
red blood cell count in a given volume of blood (x10^12/L)
What is Hct and what are its units?
haematocrit (L/L) previously known as packed cell volume and expressed as %
What is MCV and what are its units?
mean cell volume (fL) (1x10^-15L)
What is MCH and what are its units?
mean cell haemoglobin (pg) (1x10^-12g)
What is MCHC and what are its units?
mean cell haemoglobin concentration (g/L)
What is platelet count and what are its units?
the number of platelets in a given volume of blood (x10^9/L)
MCV=
Hct x1000/ RBC
MCH=
Hb/ RBC
MCHC=
Hb/ Hct
How did we used to measure WBC, RBC and platelet count?
Initially counted visually, using a microscope and a diluted sample of blood
How do we count WBC, RBC and platelet count now?
Now counted in large automated instruments, by enumerating electronic impulses generated when cells glow between a light source and a sensor or when cells flow through an electrical field
Why are blood cell parameters so important?
- The Full Blood Count (FBC) is a frequently performed blood test, often requested routinely both in GP surgeries and in hospitals
- The vast majority of patients will have a FBC checked regularly during a hospital admission
- Understanding red blood cell parameters helps in the diagnostic interpretation of FBC
What is anaemia?
reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subjected of the same age and gender
Hb concentration is reduced
Anaemia is usually due to a reduction of the absolute amount of haemoglobin in the blood stream
What else is reduced in anaemia usually?
RBC and Hct/pCV are usually also reduced
Looking at what can help suggest what the cause of anaemia is?
classification on the basis of cell size can help suggest specific causes, (not mechanism)
What are the 3 types of sizes and what colours associates with them?
Microcytic- usually hypochromic
normocytic- usually normochromic
macrocytic- usually normochromic
How much of a normal red blood cell is pale?
about a third of the diameter
- this is a result of the disc shape of the red cell; the centre has less haemoglobin and is therefore paler
WHat does hypochromia mean?
It means that the cells have a larger area of central pallor than normal
This results from a lower haemoglobin content and concentration and a flatter cell
Hypochromia and microcytosis often go together
What are poikilocytes?
abnormal shape
What should you examine when it comes to RBCs?
size
shape
colour
any abnormal shapes I.e., poikilocytes
What are the types of anaemia?
Aplastic
Iron deficiency
Sickle cell
Thalassaemia
Vitamin deficiency
What is aplastic anaemia?
body stops producing enough new blood cells
What is thalassaemia?
causes the body to have less haemoglobin than normal
It is an inherited blood disorder
What can cause increased blood loss?
hookworm (most common cause worldwide), gastrointestinal (often silent/ asymptomatic), menstrual (menorrhagia)
What are causes of iron deficiency anaemia?
Increased loss (blood loss)
Insufficient intake/ malabsorption
Increased requirements (physiological, pregnancy, infancy)
What are clinical features of iron deficiency anaemia?
pallor, fatigue, breathlessness
Failure to thrive
Koilonychia
Angular cheilitis
What does the cell look like if there is reduced MCH and MCHC, and what sort of anaemia is it?
hypochromic and microcytic
e.g., iron deficiency
What does the cell look like if there is reduced MCH, but normal MCHC, and what sort of anaemia is it?
normochromic and microcytic
e.g., thalassaemia trait
What does hypochromia correlate with?
MCHC
What are the ways to investigate haemoglobin in a lab?
electrophoresis and High performance liquid chromatography (HPLC)
What can you use high performance liquid chromatography for?
quantitation of HbA2
How do you distinguish between iron deficiency and thalassaemia trait?
Hb
MCV
MCH
MCHC
RBC
Hb electrophoresis
Ferritin
What are the 2 most common causes of microcytosis?
iron deficiency (defect in haem synthesis) and thalassaemia trait (defect in globin synthesis)
What is the key difference between alpha and beta thalassaemia?
defect in alpha chain and defect in beta chain synthesis
Do you understand this diagram about iron deficiency anaemia?
What is the treatment for iron deficiency anaemia?
iron replacement therapy e.g., ferrous sulphate tablets
When is hepcidin secreted?
It is usually secreted by the liver in response to high iron stores
hepcidin production is also increased in inflammatory states= reducing iron supply
How would you treat anaemia of a chronic disease?
Controlling the underlying disease to reduce inflammation (e.g., by treating the infection) will treat the anaemia
Do you understand this diagram about anaemia of chronic diseases?
How is vitamin B12 absorbed?
- Stomach:
B12 combines with Intrinsic factor (IF) made in the
gastric parietal cells - Small intestine:
B12-IF binds to receptors in the ileum - Vitamin B12 deficiency may result from:
inadequate intake e.g. veganism
inadequate secretion of IF: pernicious anaemia
(an autoimmune disorder)
Malabsorption e.g. coeliac disease, surgery lack of acid in stomach (achlorhydria)
What can cause macrocytic anaemia?
- Lack of vitamin B12 or folic acid (megaloblastic anaemia)
- Use of drugs interfering with DNA synthesis
- Liver disease and ethanol toxicity
- Haemolytic anaemia (reticulocytes increased)
Why does macrocytic cells appear when haemolytic anaemia occurs?
Remember:
Young red cells are about 20% larger than mature red cells so if there is an increased proportion of young red cells (polychromasia/reticulocytes) in the circulation, the average cell size (MCV) will be increased
What causes haemolytic anaemia?
The normal erythrocyte life span is 120 days
Erythrocyte function depends on:
– Integrity of the membrane –Haemoglobin structure and function – Cellular metabolism
A defect in any of these results in shortened erythrocyte survival: haemolysis:
–Membrane e.g. Hereditary Spherocytosis
–Haemoglobin e.g. HbSS (an example of haemoglobinopathy)
– Cellular metabolism e.g. G6PD deficiency
What is a megaloblast?
abnormal erythroblast in the bone marrow
- It is lager than normal and shows asynchronous nucleocytoplasmic maturation
What is megaloblastic anaemia?
it is caused by a deficiency of vitamin B12 or folate and is a cause of macrocytic anaemia
What does polychromasia describe?
Increased blue tinge to the cytoplasm of a red cell
It indicates that the red cell is young and reflects increased erythropoiesis in the bone marrow which occurs as a response to haemolysis
Polychromatic cells are larger than normal red cells I.e., polychromasia is one of the causes of macrocytosis
How can you detect young RBCs?
do a special stain, new methylene blue, for reticulocytes
Why does new methylene blue work for reticulocytes?
this stains for their higher RNA content
What does reticulocytosis mean and why may it occur?
Refers to the presence of increased numbers of reticulocytes
It may occur as a response to bleeding or red cell destruction (haemolysis)
What are the causes of normocytic anaemia?
recent blood loss
failure of production of red cells
pooling of red cells in the spleen
What are causes of recent blood loss normocytic anaemia?
gastrointestinal haemorrhage, trauma
What are causes of failure of production of red cells normocytic anaemia?
Bone marrow failure or suppression (e.g., chemotherapy)
Bone marrow infiltration (e.g., leukaemia) anaemia of chronic disease
What are causes of pooling of red cells in the spleen normocytic anaemia?
hypersplenism, e.g., liver cirrhosis
Splenic sequestration in HbSS (sickle cell anaemia: only in children <5 y/o)
What is splenic sequestration in simple terms?
Red blood cells get trapped in the spleen
What types of poikilocytes are there?
target cells
Sickle cells
Fragments
Spherocytes
Elliptocytes
Irregularly contracted cells
What is the pathophysiology of sickle cell disease?
hypoxia–>
polymerisation of HbS–>
Rigid sickling of RBCs–> 1 & 2
1…
haemolysis, reduced RBC survival–>
anaemia, jaundice, gallstones
2…
vaso-occlusion–>
bone, kidney, cerebral, retina, lung, spleen
What has a lower affinity haemoglobin, HbA or HbS?
HbS
What is the affinity for HbS?
the baseline Hb concentration in individuals with HbSS is lower than for HbA (roughly 60-80g/L in HbSS)
Does the lower affinity of HbS result in symptoms of anaemia in HbSS?
No, this can be partly explained by the oxygen-Hb dissociation curve
What is the spleen involved in?
Immune defence
Breakdown and removal of old, malformed or damaged RBCs ‘quality control’
What does repeated splenic vaso-occlusion (usually with no symptoms) in HbSS lead to?
to the spleen no longer working by the age of 5 years: this is known as ‘functional hyposplenism’
What does hyposplenism increase?
susceptibility to encapsulated bacterial infection
- immunisation
- prophylactic (preventative) antibiotics
What are target cells?
RBC with an accumulation of haemoglobin in the centre of the area of central palor
What are howell jolly bodies?
remnants of DNA from nuclei that haven’t been fully expelled by late erythroblasts during their maturation in the bone marrow
Do you think polycythaemia due to hypoxia could have any undesirable effects?
It could cause hyperviscocity and predispose to thrombosis
List a possible cause and mechanism of a raised haemoglobin concentration in: a patient with an abdominal mass?
Carcinoma of the kidney- inappropriate erythropoietin synthesis
List a possible cause and mechanism of a raised haemoglobin concentration in: a breathless cyanosed patient?
Hypoxia- appropriately increased erythropoietin
List a possible cause and mechanism of a raised haemoglobin concentration in: a patient with an enlarged spleen?
Polycythaemia vera- abnormal bone marrow function
List a possible cause and mechanism of a raised haemoglobin concentration in: a young healthy athlete?
be very suspicious- blood doping or inappropriate erythropoietin use
