Red Cells (Erythrocytes) Flashcards
Another name for red cells?
Erythrocyte (bag of haemoglobin - no organelles)
Where and from what are red cells produced, and what is the process called?
Produced in the bone marrow, derived from multipotent haemopoietic stem cells (HSCs). The process is called haemopoiesis (in adults mainly occurs in the bone marrow, especially the pelvis, femur and sternum)
What are 2 essential properties of HSCs?
- They can give rise to all mature blood cells
2. They are self-renewing
Explain what is meant by HSCs are ‘self-renewing cells’
When they differentiate, at least some of their daughter cells remain as HSCs, so the pool of stem cells is not depleted, the others differentiate to produce specific types of blood cell but cannot renew themselves
Blood cells - what is the stem cell hierarchy?
HSCs can differentiation into myeloid stem cells or lymphoid stem cells. The myeloid stem cells can differentiate to granulocytes/monocytes, erythrocytes and megakaryocytes (platelets). The lymphoid stem cells can differentiate to natural killer cells, T cells and B cells
What is the development of red blood cells called?
Erythropoeisis
Process of erythropoiesis:
Myeloid stem cell gives rise to proerythroblast. This then gives rise to early, intermediate and late erythroblasts. Then eventually, erythrocytes.
What regulates erythrocyte production?
The kidney releases erythropoietin, usually in response to hypoxia (lack of oxygen reaching tissues), which stimulates the production of erythrocytes from stem cells in bone marrow. Testosterone can also trigger the release of erythropoietin
Where are the sites of synthesis of red cells?
90% in the kidney - in the juxtatubular and interstitial cells
10% in the liver - in the hepatocyte and interstitial cells
Why is the erythrocyte a biconcave shape?
Helps them manoeuvre through small blood vessels
What do red blood cells have that allow it to carry oxygen?
Haemoglobin (Hb)
Structure of Hb A (in adults):
4 subunits - each composed of a globin chain (2 alpha and 2 beta) bound to a haem group. The haem group contains an Fe2+, in a ring called porphyrin
How does the structure of Hb F (in fetal Hb) differ?
2 alpha and 2 gamma (light beta) globin chains, which gives it a higher affinity to O2 compared to Hb A
How many oxygen molecules can each Hb bind to (and why)?
4 - Each Hb has 4 Fe2+ ions, each binding to one O2 molecule
Which 2 things facilitate the transport of oxygen in Hb?
- Sigmoid oxygen dissociation curve - Hb’s affinity for oxygen increases as successive molecules of oxygen bind, except the last O2 molecule that rarely binds
- Bohr Effect - lowered pH (due to metabolic activity) causes Hb to change shape ad release the oxygen molecules
What is the oxidised form of Hb called, and what is the charge of the iron ion?
Methaemoglobin
Fe3+
From which source and where in the body is iron absorbed from?
Food, duodenum
Best absorbed as Fe2+ but Fe3+ can also be absorbed
Which factors increase or decrease iron absorption?
Increase: Vitamin C and Folic Acid
Decrease: Phytates (e.g. found in soya beans)
Why is absorption of iron strictly controlled?
How much iron is absorbed daily?
The body is unable to get rid of excess iron (via excretion), and iron is toxic to organs e.g. heart and liver.
1-2 mg of iron absorbed daily
Where can iron be stored in the body?
Splenic macrophages
Which chemical controls absorption of iron and how?
Hepcidin - released from the liver, regulates a duodenum enterocyte cell called ferroportin, and so controls the entry of iron into the plasma. It also blocks absorption and release of storage iron
How does hepcidin synthesis, erythropoietic activity and ferroportin link together?
Hepcidin synthesis is suppressed by erythropoietic activity: this ensures iron supply by increasing ferroportin in the duodenum enterocyte, which increases iron absorption
How is iron absorption controlled when storage iron high?
Hepcidin synthesis is increased, which binds and degrades ferroportin
What 2 substances required for DNA Synthesis?
Vitamin B12 and Folic Acid (required for thymine synthesis)
What does deficiency in Vitamin B12 and Folic Acid result in?
Affects rapidly dividing cells e.g. in bone barrows
Potential sources of Vitamin B12 and Folic Acid?
Vitamin B12: Meat, fish, liver & kidney, eggs etc
Folic Acid: Green leafy vegetables, Cauliflower, Brussels sprouts, Liver & kidney
How is Vitamin B12 absorbed?
In the stomach B12 combines with Intrinsic factor (IF) forming B12-IF, which can bind to receptors in the ileum
Potential reasons for Vitamin B12 deficiency?
Veganism/ inadequate intake, inadequate secretion of IF, malabsorption
How long do red blood cells last?
120 days in circulation until it is finally destroyed by phagocytic cells of the spleen
Process of Erythropoiesis:
Proerythroblast, then early, intermediate and late erythroblast, then Polychromatic erythrocyte, then mature erythrocyte
What is the red blood cell terminology to describe the size of the RBC?
Microcytic - smaller / an anaemia with small red cells
Normocytic - normal / an anaemia with normal red cells
Macrocytic - larger / an anaemia with large red cells
How do red blood cells stain and why?
Normally, 1/3 of the diameter is pale due to the biconcave shape, so the indent has little Hb and therefore stains less (paler)
What is the red blood cell terminology to describe the colour of the RBC?
Hypochromia - larger area of central paleness than normal
Polychromasia - increased blue tinge to the cytoplasm of a red cell
What does polychromasia indicate?
The cell is young
Methods to detect a young cell?
- Polychromasia
- Reticulocytosis, increased number of reticulocytes (immature red blood cells). Using a special stain (new methylene blue) to stain higher RNA content, so to detect reticulocytes
What is the red blood cell terminology to describe the variations in shapes and sizes of the RBC?
Poikilocytosis – red cells show more variation in shape than is normal
Anisocytosis – red cells show more variation in size than is normal
What are the 6 different shapes of Poikilocytes?
Spherocytes - spherical
Irregularly contracted cells - irregular?
Sickle cells - Crescent shape
Target cells - red dot at the centre (due to accumulation of Hb there)
Elliptocytes - oval shape
Fragments - piece of red cell
In what conditions may target cells occur/appear?
Obstructive jaundice
Liver disease
Haemoglobinopathies
Hyposplenism
How do sickle cells arise?
Polymerisation of Hb S
Is sickle cell anaemia dominant or recessive?
Recessive
How is Hb S different from Hb A?
When deoxygenated, it is less soluble than Hb A
Why do people who carry only one copy of the sickle cell allele not develop sickle cell?
1 copy of the gene results in only about 45% Hb S, so there is still 55% Hb A, therefore not enough Hb S to form sickle cells
What is the difference between symptoms and signs?
Symptoms - what the patient feels (i.e the concerns they voice)
Sign - Abnormal physical things (i.e a lump, rash etc)
Blood count interpretation: WBC RBC Hb PCV Hct MCV MCH MCHC Platelet count
WBC - white blood cell count, the number of white cells in a given volume of blood
RBC - red blood cell count, the number of red cells in a given volume of blood
Hb - haemoglobin concentration
PCV - packed cell volume, the proportion of a column of centrifuged blood occupied by red cells (now replaced by the haematocrit)
Hct - haematocrit, equivalent to the PCV but not measured by centrifugation
MCV - mean cell volume, i.e. the average size of the red cells
MCH - mean cell haemoglobin, i.e. the average amount of haemoglobin in a red cell
MCHC - mean cell haemoglobin concentration, i.e. the average concentration of haemoglobin red cell
Platelet count - the number of platelets in a given volume of blood
What is anaemia?
Low blood haemoglobin concentration
Measurements used for diagnosing different types of anaemia:
(Low) Concentration of haemoglobin
(Low) Red cell count
(Low) Haematocrit (packed cell volume = volume percentage of erythrocytes in blood (usually around 45%). To measure haematocrit you centrifuge a blood sample and the proportion of total bloodvolume consisting of erythrocytes is the haematocrit.
(Low) Mean Cell Volume/Mean Corpuscular Volume - the average volume of a single red blood cell
Thinned blood - spread out red blood cells
What are the three types of anaemia?
Microcytic (small MCV)
Caused by menstruation, GIT lesions or cancer
Normocytic (normal MCV)
Caused by acute blood loss
Macrocytic (high MCV)
DNA synthesis and cell division fail and there is reduced cell division of progenitor cells so you get larger erythrocytes.
Caused by vitamin B12 deficiency (pernicious anaemia)
What is the normal range?
Based on 95% of the healthy population’s data, i.e in anormal distribution curve, the mean +or- 2 SDs
What is the reference range?
Range of values that is deemed normal for a physiologic measurement in healthy people, used as a comparison line to interpret patient’s data
How is the reference range derived?
Samples are collected from healthy volunteers with defined characteristics
They are analysed using the instrument and techniques that will be used for patient samples
The data are analysed by an appropriate statistical technique
What factors cause ‘normal’ to differ?
Age, Gender, Physiological state (e.g. pregnancy), ethnic origin, altitude (affects Hb), smoking, alcohol intake
How to interpret red cells on a blood count and film?
Anaemia? (clues in the blood count?) Clinical history? Size? Shape? Age? (polychromasia) Poikilocytes?
