Yaffas notes for Case 7 Flashcards
what do all blood cells begin their life as and where
pluripotential haemopooietic stem cells (PHSC) and in the bone marrow
what is a committed cell that produces erythrocytes called
CFU-E
what cells give rise to granulocytes, erythrocytes, monocytes and megakaryocytes
CFU-GEMM
what do PHSCs present with on their surface
CD34+ and CD38-
what does the stem cell factor do. SCF
synergises with IL-3 and GM-CSF to increase proliferation of stem cells
what is GM-CSF necessary for
growth and development of granulocyte and macrophage progenitor cells
Stimulates myeloblasts and monoblasts
what does G-CSF act on
acts on precursor cells which give rise to neutrophils
what does M-CSF play a role in
proliferation and differentiation of haematpoietic stem cells to produce monocytes and macrophages
what does IL-3 do
works in conjunction with GM-CSF to proliferate most of the haematopoietc progenitor cells
what does IL5 do and what produces it
produced by T lymphocytes and plays a role in growth and differentiation of eosinophils
where is thrombopoietin produced
mainly in the liver
what does thrombopoietin stimulate
megakaryocytes and platelet production
differentiation inducers factors
PU.1
GATA.1
what does PU.1 cause
differentiation of cells along the myeloid lineage
what does GATA.1 cause
differentiation of cells along the eryhtropoeitc and megakaryocytic lineages
thickness and diameter of RBCs
7.8 micrometers in diameter and 2.5 micrometers in thickness
what is the average volume of a red blood cell
90-95cm cubed
what is the normal range of the mean corpuscular volume
80-99fL
where are erythrocytes produced in early weeks of embryonic life
in the yolk sac
where are erythrocytes produced in the middle trimester of gestation
liver (mainly), spleen and lymph nodes
where are erythrocytes produced in the last month of gestation and after birth
RBC’s produced in the bone marrow
first cell that can be identified as belonging to the red blood cells series:
the pro erythroblast
this is formed from the CFU-E stem cells
how much haemoglobin do proerythroblasts have
very little haemoglobin
what forms polychromatophil and orthochromatic erythroblasts
basophil erythroblasts
what comes after the orthochromatic erythroblast:
reticulocyte
how long does it take to reach the reticulocyte stage of the RBC
5 days
final cell produced
mature erythrocyte - takes 1 to 2 days
where is erythropoietin produced
the kidney
what is erythropoietin produced as a response to
low tissue oxygenation
what stimulates erythropoietin production
noradrenaline and adrenaline
what does erythropoeitn stimulate
production of proerythroblasts from hematopoietic stem cells
life span of a RBC
120 days
what happens when a RBC goes past the 120 days
it becomes more fragile and cell ruptures during passage through the red pulp of the spleen. the content of the red blood cell (haemoglobin) is released and is phagocytose by the macrophages in many parts of the body.
what cell phagocytoses RBCs
Kupffer cells of the liver and macrophages of the spleen and the bone marrow
what does this cause
release of Fe into the blood
what carries Fe to the bone marrow for production of new erythrocytes
transferrin
Fe can be carried to the bone marrow, but where else?
the liver
how Is iron stored In the liver
as ferritin
what happens to the porphyrin portion of the haemoglobin molecule
converted by the macrophages to bilirubin, which is released into the blood and later removed form the body by secretion through the liver into bile
diagram of Haematopoeisis
average amount of haemoglobin per 100ml of cells in men
15g of haemoglobin per 100mls
average amount of haemoglobin per 100mls in females
14g of haemoglobin per 100mls
how much oxygen is each gram of haemoglobin able to combine with
1.34mls of oxygen
chains that combine to form haemoglobin
2 alpha chains and 2 beta chains
how much oxygen can be transported by each haemoglobin molecule and why
four molecules
each haemoglobin chain has a heme group containing one atom of iron and because there are four haemoglobin chains (alpha and beta) in each haemoglobin molecule, one find four iron atoms in each haemoglobin molecule, each of these can loosely bind with one molecule of oxygen making a total of four molecules of oxygen being transported by each haemoglobin molecule
HbA occurs in what percentage of adults (normal and most common)
97%
what does 2,3-DPG do
binds to haemoglobin molecule and lowers its oxygen affinity
what does the liver secrete into the bile
apotransferrin which flows through the bile duct into the duodenum where it enters the duodenal circulation
what does the binding of apotransferrin and free iron in the duodenal circulation form
transferrin
where is transferrin transported
either to the liver or bone marrow
what happens to transferrin in the liver
enters the hepatocytes and combines with apoferritin forming ferritin
what happens to transferrin in the bone marrow
binds to receptors on the eryhtroblasts, delivering iron to the mitochondria for the production of haemoglobin
granulopoiesis
- myeoblasts of varying size, large nucleus and no cytoplasmic granules are the first committed cells
what do myeoblasts form
promyelocytes which comprise of primary cytoplasmic granules
what do promyelocytes form
myelocytes depending on the cell type
what do myelocytes form
metamyelocytes which are non-dividing cells with an indented nucleus and many cytoplasmic granules
what percentage of the circulating leucocytes are neutrophils
40-75%
how many lobes do mature leucocytes have
5 lobes
eosinophils constitute what percentage of leucocytes
1-6%
what percentage of leucocytes do basophils consitute
less than 15
what percentage of leucocytes do basophils consitute
less than 1%
monopoieses timeline
- monoblast is first committed cell
- this divides and differentiate into a promonocyte
- this differentiates into a mature monocyte
percentage of leucocytes that monocytes constitute
2-10%
how long do monocytes circulate for before turning into macrophages in tissues
2-4 days
where does lymphopoeiss occur in a foetus and an adult
the liver in a foetus
the bone marrow in an adult
what do B lymphocytes mature into
plasma cells
where are plasma cells formed
in the lymph nodes and themselves produce antibodies
where to T Lymphocytes mature
in the thymus
percentage of circulating leucocytes that lymphocytes make up
20-50%
3 reasons for anaemia
- reduced production of RBCs
- increased loss of RBCs
- haemoglobinopathies: sickle cell anaemia and thalassaemia
what is macrocytic anaemia a result of
vitamin B12 deficiency, folate deficiency and alcohol excess (liver disease)
what is normocytic anaemia a result of
acute blood loss, anaemia of chronic disease, pregnancy and bone marrow failure/supression
what is microcytic anaemia a result of
iron-deficiency anaemia or thalassaemia
reduced production of RBCs is a result of what deficiencies
iron deficiency
folate deficiency
Vitamin B12 deficiency
what is reduced production of RBCs a result of (non-deficiencies)
anaemia of chronic disease (rheumatoid arthritis - decreases folate)
cancers e.g leukaemia
increased destruction and loss of RBCs is a result of
- blood loss
- sickle cell disease
- thalassaemia
- erythrocyte membrane defects
- cancers
- haemolytic disease of a newborn
- incompatible blood transfusion
blood film appearances
treatment for iron deficiency anaemia
ferrous sulphate
what is vitamin B12 anaemia caused by
malabsorption of the vitamin
what is pernicious anaemia
term used to describe vitamin B12 deficiency resulting from the inadequate gastric production or defective function of intrinsic factor
treatment for pernicious anaemia
folate
intramuscular vitaminB12
causes of folate deficieny anaemia
- diet/decreased intake
- increased requirements
- impaired utilisation
treatment for folic deficiency anaemia
oral folic acid
two haemoglobinopathies
sickle cell disease
thalassaemia
what is the genetic variation in sickle cell disease
genetic variation in the beta global chain of the Hb molecule (HbS)
what happens when a person has sickle cell disease
the Hb molecule becomes unstable in low oxygen condition leading to the formation insoluble rigid chains
this causes vasoconstriction-occlusion and destruction of the red cell - haemolysis
pathogenesis of sickle cell disease
HbS molecules undergo polymerization (combine) when deoxygenated.
Initially the red cell cytosol converts from a freely flowing liquid to a viscous gel as HbS aggregates form.
With continued deoxygenation aggregated HbS molecules assemble into long needle-like fibres within red cells, producing a distorted sickle shape.
The presence of HbS underlies the major pathologic manifestations:
Chronic haemolysis
Microvascular occlusions
Sickle red cells express higher than normal levels of adhesion molecules and are sticky.
Tissue damage: this is as a result of the microvascular occlusions causing certain tissue to become hypoxic as a result of ischemia.
clinical features of SCA
anaemia stroke acute chest syndrome impaired growth and development chronic organ damages
treatment for sickle cell anaemia
bone marrow transplants
prophylactic antibiotics due to increased susceptibility of infections
blood transfusion to reduce the amount of HbS cells
what is thalassaemia
a group of inherited disorders resulting in reduced production of one or more global chains.
this results in an imbalance of globin chains ad many pathological effects
pathological effects of thalassaemia
- damage to red cell precursors - leading to ineffective eryhtropoeisis
- damage to mature blood cells leading to haemolytic anaemia
what type of anaemia does thalassamia mainly cause
microcytic anaemia
what are the two main types of thalassaemia
alpha thalasseamia
beta thalassaemia
clinical classification of thalassaemia:
- Thalassaemia Major Continual transfusion dependent - Thalassaemia Intermedia Less severe anaemia and can survive without regular blood transfusions - Thalassaemia Minor/ Carrier Asymptomatic carrier
clinical features of thalassaemia
- problems due to anaemia e.g failure to grow and develop
- problems due to iron overload - failure of grow and mature
blood group table
