The Erythrocyte Flashcards
How much blood does a 70kg man have
5.6L
What percentage of blood is water
78%
What temperature is blood
38 degrees
What is the pH of blood
7.35-7.45
What does blood carry to tissues
(7)
Oxygen
Water
Electrolytes
Hormones
Vitamins
Antibodies
Heat
What does blood carry away from the tissues
Waste matter (urea)
Carbon dioxide
What percentage of blood is plasma
55%
What percentage of blood is erythrocytes
45%
What are the formed elements of blood
Red cells (99%)
Platelets (1%)
WBC (1%)
Describe the structure of a rbcs
(4)
Biconcave disc to enhance the diffusion of gases by increasing surface area
Thin to enable oxygen to diffuse rapidly and alse increase flexibility
When mature they don’t have nuclei, mitochondria or other organelles
Packed full of haemoglobin
What is the diameter of an rbcs
7-8 micrometers
For how long do rbcs survive
120 days
What conditions are needed for an rbc to survive 120 days
Intact red cell membrane
Normal haemoglobin structure
Normal metabolic pathways
What happens if rbcs are damaged or not functioning correctly
(3)
They are removed by macrophages
The haemoglobin components are recycled
- iron is recycled
- globin is broken down into amino acids and haem is excreted in bile
What enzyme is found in rbcs which is involved in gaseous exchange
Carbonic anhydrase
What does carbonic anhydrase do
It takes CO2 and H2O and catalyses the creation of a stable molecule called bicarbonate
What does bicarbonate do
This is an easier form of carrying CO2
This acts as a buffer for the blood
What is the chemical formula for bicarbonate
HCO3-
Why is HCO3- considered more efficient of a molecule
It dissolves much better than CO2
Great quantities of CO2 can be transported this way without needing to be inside the small rbc
What happens when HCO3- dissolved in the blood arrives in the capillaries of the lung
HCO3- is converted back to gaseous CO2
CO2 then diffuses out into the lungs where it is breathed out
How long does it take reticulocytes to become rbcs
approx 2 days
What does increased reticulocytes mean
Disease or mass bleed
The bone marrow is under pressure to replace rbcs
What happens during the development from a proerythroblast to an erythrocyte
(4)
Cell keeps getting smaller
Cytoplasmic to nuclear ratio gets bigger
Haemoglobin accumulates
Nucleus shrinks and is eventually dispelled
List the cells involved in the maturation of the erythrocyte
(7)
Hemocytoblast
Proerythroblast
Early erythroblast
Late erythroblast
Normoblast
Reticulocyte
Erythrocyte
What cell type is involved in phase 1 of erythrocyte development
Early erythroblast
What happens in phase 1 of erythrocyte development
Ribosome synthesis
What cell types are involved in phase 1 of erythrocyte development
Late erythroblast
Normoblast
What happens in phase 2 of erythrocyte development
Haemoglobin accumulation
What cell type is involved in phase 3 of erythrocyte development
Reticulocyte
What cell types of involved in the progression from normoblast to reticulocyte
Pronormoblast
Basophilic normoblast
Polychromatophilic normoblast
Orthochromatic normoblast
Reticulocyte
What was the role of bone marrow macrophages originally thought to be
That they scavenged and phagocytosed extruded nuclei
What is the role of bone marrow macrophages
Providing cytokines and other signals needed to promote erythropoiesis
How do macrophages promote proliferation of pro/erythroblasts into more mature cells
(2)
The close physical proximity of the macrophage brought about by the interaction of adhesion molecules on both cell types
Its characteristic cytoplasmic protrusions
What happens to erythroblasts which have been stimulated to mature
(2)
They move to the sinusoids of the bone marrow which are close to blood vessels
This facilitates the migration of reticulocytes and erythrocytes into circulation
What is the erythroblastic island in the bone marrow
(3)
Erythroblastic islands are specialized microenvironmental compartments within which erythroblasts proliferate and differentiate.
These islands consist of a central macrophage that extends cytoplasmic protrusions to a ring of surrounding erythroblasts
Central macrophage provides further cues to induce erythroblast differentiation, expansion and haemoglobinisation
What happens after erythroblasts have interacted with macrophages?
Erythroblasts extrude their nuclei
Nuclei are phagocytosed by macrophages
Reticulocytes are released into circulation
What are reticulocytes
rbcs with remnants of ribosomal RNA
How do we identify reticulocytes
RNA reacts with methylene blue dye (basic dye) to produce a blue precipitate
Can be counted using a flow cytometer and CD71
What is a normal reticulocyte count
Between 0.2 and 2%
Why would one have high reticulocytes
(4)
Bleeding
High altitude
Haemolytic anaemia
They are a baby
Why would one have low reticulocytes
Aplastic anaemia
Iron deficiency anaemia
Radiation
What growth factors control erythropoiesis
SCF
EPO
What is EPO
An essential erythroid specific factor
A hormone produced in the pertubular interstitial cells of the kidney (90%) and the liver (10%)
What is the molecular mass of EPO
34kDa
What happens when EPO is activated
(3)
EPO signalled when blood volume is low
EPO receptor engagement results in JAK2 pathway activation
This acts on the BFU-E (burst forming unit)
Where is JAK 2 receptor found
On developing rbcs in body
What pathway is mutated in a lot of leukaemias
JAK pathway
What activates EPO
Tissue hypoxia
EPO promotes cell division and differentiation into normoblasts in what cells
(5)
CFU-GEMM
BFU-E
CFU-E
Pro-Normoblast
Basophilic normoblast
What are the effects of EPO
Shorten the cell cycle time of dividing cells
Shorten the maturation time
Inhibit apoptosis
Promotes reticulocyte release from the bone marrow
What causes macrocytes
(3)
Liver disease
Alcoholism
-> can be oval shaped in megaloblastic anaemia
What causes target cells
(4)
Iron deficiency
Liver disease
Haemoglobinopathies
Post-splenectomy
What are stomatocytes
rbcs with a rectangular pale patch in centre
What causes stomatocytes?
Liver disease
Alcoholism
What causes pencil cells
Iron deficiency
What are echinocytes
Spiky rbcs
What causes echinocytes
(3)
Liver disease
Post-splenectomy
Storage artefact
What are acanthocytes?
Misshapen rbcs
What causes acanthocytes
Liver disease
Abetalipoproteinaemia
Renal failure
What causes microspherocytes?
(3)
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Speticaemia
What causes rbc fragments (6)
DIC
Microangiopathy
HUS
TTP
Burns
Cardiac valves
What are elliptocytes
Oval shaped rbcs
What causes elliptocytes
Hereditary elliptocytosis
What causes tear drop poikilocytes
(2)
Myelofibrosis
Extramedullary haemopoiesis
What causes basket cells (2)
Oxidant damage e.g. G6P deficiency
Unstable haemoglobin
What causes sickle cells
Sickle cell anaemia
What causes microcytes
(2)
Iron deficiency
Haemoglobinopathy
List some RBC inclusions
(6)
Howell-Jolly body
Pappenheimer bodies (Siderotic granules)
Basophilic stippling
Malaria parasite
Reticulocyte RNA
Heinz bodies
What type of staining is needed for RNA and Heinz bodies
New Methylene Blue
What are Heinz bodies
Oxidised denatured Hb
What are siderotic granules
Granules containing iron
Appear purple with conventional staining and blue with Perls stain
What is Howell-Jolly body
DNA remnant
What is basophilic strippling
Denatured RNA
What do we use red cell indices for
Classification of anaemia
What are the three red cell indices
MCV
MCH
MCHC
What is MCV
Average volume of the red cell, expressed in femtolitres (fL or 10^-15L)
What does MCV suggest
Cells are normocytic, macrocytic or microcytic
What is the equation for MCV
(Hct% x10)/ RBC (x10^12/L)
What is MCH
The average weight of Hb in the red cell, expressed as picograms (pg or 10^12g)
What is MCH
The average weight of Hb in the red cell, expressed as picograms (pg or 10^12g)
What is MCH
The average weight of Hb in the red cell, expressed as picograms (pg or 10^12g)
What does MCH suggest
RBCs are normochromic or hypochromic
What is the equation for MCH
(Hb g/L)/ RBC (x10^12/L)
What is MCHC
Average concentration of Hb in the RBC volume expressed as grams of haemoglobin
Reported as g/L or g/dL
What is the equation for MCHC
(Hb g/L x 100)/Hct %
The loss of what molecules determine the time of death for rbcs
(3)
When rbcs run out of G6PD or pyruvate kinase
They can’t replenish these so the cell begins to lose its shape and flexibility
This damage is recognised by phagocytic cells
What are the two types of rbc haemolysis?
Extravascular haemolysis (90%)
Intravascular haemolysis (10%)
Where does extravascular haemolysis occur
Spleen
Liver
Where does intravascular haemolysis occur
Within the circulation
How is haem broken down
(2)
The protoporphyrin ring is broken down to iron, carbon monoxide and biliverdin
Biliverdin is further broken down into bilirubin by haemoxygenase
