Case 7 Flashcards
what does blood regulate
body temp
pH
solutes
restricts osmosis into tissues
how long do erythrocytes survive in the circulation
120 days
what are erythrocytes broken down by
the liver and spleen
what is formation of erythrocytes controlled by
erythropoietin
where is erythropoietin produced by
kidneys in response to low oxygen levels
what does each molecule of haem contain
an iron atom
how many molecules of oxygen does haem bind
one
what does haemoglobin consist of
four peptide chains or globins and four haem molecules. it is a balance of alpha and beta chains
what does proliferation of RBC precursors require
DNA synthesis
protein synthesis
what two B-complex vitamins play a critical role
- folate 950-1000ug/day (required for synthesis pf purines and pryimidines)
- vitamin B12 - required for snyhrisis of some amino acids
anaemia value for men
<13.5 g/dl
anaemia value for women
<11.5 g/dl
symptoms of anaemia
anaemia based on what causes:
- failure of production
- defective red cells
- loss/destruction of red cells
anaemia based on red cell size
- microcytic
- normocytic
- macrocytic
acute blood loss
dilution to maintain circulation volume
chronic blood loss
peptic ulcers, menorrhagia, piles, worms etc
what deficiencies cause anaemia
iron vitamin 12 folate protein vitamin C
approach to the investigation of anaemia
levels of high red cells and increased production
polycythemia
what is saline solution in giving blood
SAGM which stands for saline-adenine-glucose-mannitol.
how much plasma does standard red cell component contain
20mls
What is large MCV a sign of
dtysfunctioning bone marrow
signs of polycythemia
red/bluish skin
complex
twin to twin transfusion
what is a low white cell count called
leukopenia
what is having too many platelets called
thrombosis cytosis
what is too little platelets called
thrombocytopenia
what is bone marrow a site of
postnatal haematopoiesis
leukemia types
how many children cured from ALL
85% of children
how many children cured from AML
70% cured
morphology of AML
auer rods, cytoplasmic granules
morphology of ALL
no auer rods or granules
how much of blood is formed elements - cells
45%
how much is white blood and platelets
less than 1%
diagram of haematopoieses
lifespan of platelets
9-10 days
lifespan of leukocytes
a few days to a few years
how many new red blood cells and platelets a day
175 billion
where is earliest site of haematopoieiss
the yolk site
when does it change from primary to secondary
at 2 months
where does haumatopoeisis move after yolk sac
foetal liver and spleen
2-7 months where does haematopoeiisis take place
liver and spleen
5-9 months where does haematopoiesis take place
bone marrow
where in the adult does haematopoieis take place
vertebrae, ribs, sternum, skull, sacrum and pelvis and demur
at birth what type of bone marrow is present
red bone marrow
what kind of tissue is red marrow
haemotopoietic tissue
stromal cells:
connective tissue cells of any tissue - fibroblasts, fat cels, endothelial cells, reticulum cells and macrophages
what do stromal cells express
adhesion molecules, signal the differential cell, secrete growth factors
what is the state of quiescence
a state of reversible growth arrest
what kind of cells are haemopoeitc cells
self renewal cells and at least some of their daughter cells will be haemopoietic stem cells so the pool of stem cell is not depleted
where do all blood cells originate from
bone marrow
what cell type do all cells originate from
HSC - capable of self renewal and differentiating into other cells
what cells do pluripotential haematopoieitc stem cells give rise to
lymphoid stem cells which give rise to lymphocytes
what do myeloid stem cells give rise to
neutrophils eosinophils basophils monocytes erythrocytes platelets
what is another name for a myeloid stem cell
CFU-GEMM cell
what does CFU stand for
colony forming unit
what does the G stand for
granulocytes
what does the e stand for
erythrocytes
what do the two M’s stand for
monocyte and megakaryoxcyte
erythropoiesis mechanism
Proerythroblast: large cell with cytoplasm that stains dark blue
Gives rise to erythroblasts (early and late)
Normoblasts: smaller cells cytoplasm starting to stain lighter blue, late normoblasts have extruded nucleus (haemoglobin production takes place before it Is lost, 65% of production has taken place by this stage)
Reticulocyte: contains some ribosomal RNA, circulates in peripheral blood (1-2 days)
ENDPOINT: mature erythrocyte: RNA lost
duration: approx 7 days
Lifespan: 120 days
175 billion produced per day
RBC growth factor and size
7.5um and erythropoietin
thrombopoiesis
process of endomitosis is produce megakaryoblasts
Replication of chromosomes occurs but cells don’t divide (endomitotic replication)
Cells become larger
Only fully mature, endomitosis ceases resulting in granulated cytoplasm
Process takes 2-3 days
Each megakaryocyte “fragments” produces around 4000 platelets
Platelets: no nucleus 2-3um in diameter Haemostasis Granules Thrombopoietin
monopoiesis
monoblast: first committed cell
Promonocyte: large cell with indented nucleus only found in bone marrow
monocytes staty for 20-40 hours in peripheral blood circulation
Nucleus: kidney shape
Monocytes migrate to tissues and mature into macrophages
granulopoeisis
Myeloblast: varying size, large nucleus and no cytoplasmic granules
Form promyelocytes: primary cytoplasmic granules
Myelocytes: smaller cells with specific cytoplasmic granules, no noticeable nucleoli
Metamyelocytes: indented or horse-shoe nucleus, lots of cytoplasmic granules
neutrophils
band neutrophils form neutrophils - distinct nuclear lobes (2-5)
Enter circulation at this stage and mature in circulation
Mature neutrophils (polymorphonuclear neutrophils): ingest microorganisms, help defence of body
Approx 14 days for myeloblasts to form mature cells which are released into peripheral blood
Average lifespan in circulation is around 5 days with a further 1-2 days in tissues
Most abundant white blood cell
basophils
usually two nuclear segments, cytoplasmic granules contain heparin and histamine
Rare in normal peripheral blood (less than 1% of leukocytes)
Mature into tissues to form mast cells??
Mast cells: lifespan weeks to months
Both play a role in hypersensitivity - release inflammatory molecules such as histamine
Life span thought to be around 60-70 hours
eosinophils
larger cytoplasmic granules, tend not to have more than 3 nuclear lobes
1-4% of circulating leukocytes
Provide protection against parasites
Involved in allergic responses
Around 8-12 hours lifespan in circulation
Further 8-12 days in tissue
what type of stain is used for blood
Romanowsky type stain
lymphopoiesis
lymphocyte production T lymphocyte tend to mature in thymus B Lymphocytes differentiation in foetus occurs in liver but in adults occurs in bone marrow B lymphocytes mature in to plasma cells Plasma cells are formed in lymph nodes
what transcription factor regulates myeloid lineage cells
PU.1 -protein that in humans is encoded by the SPI1 gene.
what transcription factor regulates differentiation along eryhtopoeitic and megakaryocytic cell lineages
GATA.1
growth factors that play a role in haematopoiesis
SCF stem cell factor
GM-CSF granulocyte macrophage colony-stimulating factor
G-CSF granulocyte colony-stimulating factor
M-CSF macrophage colony-stimulating factor
Interleukin 3
Interleukin 5
Erythropoietin
Thrombopoeitin
erythropoietin
regulates erythropoiesis
Mainly synthesised in kidneys and liver
Reduction in red cell number results in decreased oxygen to tissues
Development of hypoxia in kidneys and liver
Leads to increased production of red blood cells
This corrects hypoxia and EPO synthesis switched off
thrombpoitein
mainly produced in the liver
Stimulates megakaryocytic and platelet production
stem cell factor synthesis
synthesises with cytokines such as IL3 and GM-CSF to increase proliferation of stem cells
interleukin 3
works in conjunction with GM-CSF to proliferate most haempoeitic progenitor cells
what is IL5 produced by
produced by T lymphocytes
GM-CSF
necessary for growth and development of granulocuye and macrophage progenitor cells. also stimulates myeoblasts and mono blasts
M-CSF
plays a role in proliferation and differentiation of haemopoietic stem cells to produce monocytes and macrophages
G-CSF
is similar to M-CSF but acts on the precursor cells which give rise to granulocytes
journey of blood in transfusion
donor NHS blood and transplant Hospital blood bank ward area patient
haemoglobin levels safe to give blood
men: >135g/L
women: >125g/L
what viral tests are carried out on the blood
syphilis HIV hep b hep c hep e
what specific virus will be looked for on the first visit in giving blood
HTLV
why will a small number of patients be tested for cytomegalovirus CMV
because some patients need CMV negative blood firstly being neonates and pregnant women
how much of blood is plasma
55%
what is plasma mixed with
cryoprecipitate -a plasma-derived blood product for transfusion that contains fibrinogen (factor I), factor VIII, factor XIII, von Willebrand factor, and fibronectin.
what is cryoprecipitate
rich in fibrinogen and derived from plasma
fresh frozen [plasma imported
if have an inherited blood disorder that doesn’t have a clotting factor means you have to use important plasma
where are pooled platelets from
4 different donors
red cell transfusion
provided in leucodepleted ‘units’ measuring approximately 280ml
Each unit of red cell rises the Hb by approx 10g/L
Transfused over 2-4 hours
Patients should receive written information prior to receiving a blood transfusion including the risks of reaction and viral transmission
Storage: Temp - 4 degrees +/- 2 degrees
Shelf life: up to 35 days
platelet transfusion
each ‘ATD’ - adult therapeutic dose is ‘pooled’ from 4 different platelet donations
One ATD of platelets would be expected to rise the platelet count by 20-40 x10 to the power of 9, we can check this by doing an increment
Given over 30 mins
Storage: agitation
Temp: 20-24 degrees
Shelf life: 5 days (7 days if bacterial screening)
red cell groups
what is Leinsteiner’s ale
if you have got a blood group antigen on your red cell surface then you will have the opposite antibody in your plasma
forward typing sampling method
adding patient’s red cells to the first four columns
Does the patient have A antigen expressed on the cell surface?
Does it have B?
Does it have D? Don’t call them Rhesus anymore as associating with monkeys
how to tell if antigen is present in the blood test
there is a line at top which means its present and if its at the bottom its not present
what is the reverse group function of a blood test for typing
adding patients plasma to the two end columns
Does the patient have anti-A?
Does the patient have anti-B?
the Kleinhauer test
when a baby is born to a D negative mum, we take a sample from the mum after we find out if baby is positive or negative
If baby is negative there is no issue
But if baby is positive then we do this test to quantify any foetal blood we can see in mothers circulation
Add an acid buffer to the blood film and by doing so it will denature adults’ haemoglobin, the baby has HbF (foetal) differentiate between cells of mother and baby
HbA cells will all denature and become ghosts, and HbF cells will show up and know therefore they are from the baby
what happens if D positive cells go into negative D mum
need to provide anti D for mum to mop up the D positive cells as we don’t want mum to form anti D herself. if she does, subsequent pregnancies can result in haemophiliac disease of the baby. means that they can attack the baby cells if they recognise them as not self and make the baby incredibly unwell
what is flow cytrometry
looking at the use of immunoglobulins to stick on to proteins and looking for expression of the D proteins. more accurate.
how to reduce infection risk
donor lifestyle questionnaire Cleaning and preparing the donor arm Diversion pouch - first part goes into a different sack which puts the first bit of blood that touches the skin and do tests on this part Donor viral testing Leucodepletion non-UK plasma and viral activation Platelets- BACT/ALERT CMV negative components (neonates and pregnant women) Avoid unnecessary transfusion
TACO checklist
NICE quality standards 2016
oxygen delivery
oxygen content of arterial blood x cardiac output
carriage of oxygen in solution
oxygen not very soluble in plasma
About 3ml O2 per litre
Resting O2 of 250ml/min
With 100% oxygen extraction need resting cardiac output of 80L/min
what is the resting cardiac output
5L/min
how much oxygen can a gram of Hb hold
1.3 mls
oxygen content of arterial blood
200ml/L
what happens when O2 binds with heme
general reconfiguration of the whole molecule when 02 binds and when changes from T shape to R shape
oxygen content of arterial blood equation
(haemoglobin conc x % saturation of Hb) + dissolved O2
effect of temp on saturation
middle line is the norm
Right shifting means there is a reduced affinity of O2 for Hb
Left shifting reflects an increased affinity of O2 for Hb so that at the same partial pressure you have an increase in saturation
increased temp means decreased affinity, curve shifts to the right and for the same PO2, saturation is reduced
effect of pH on saturation
decreased pH (increased acidity)
decreased affinity
shift to the right
for there same PO2, saturation is reduced
what is best pH and temp for offloading of O2 in tissues
decreased pH and increased temp both favour offloading of O2
effect of 2,3 DPG
increased 2,3DPG we have deceased affinity and shift to the right
reduce the binding of oxygen to Hb
stored blood is low in 2,3DPG and so has a high affinity for oxygen
changes in global chains with development
muscle oxygen stores
myoglobin
how many times great is CO affinity for Hb than O2
250 times
principles of pulse oxumetry
red line indicates it is full saturated and deoxygenated blood absorbs more red light and has a blue colour
pulse wave of oximetry
why is HbS so prevalent in SA and Asia
because it provides an advantage against malaria
haemoglobin and iron metabolism
what is the predominant type of haemoglobin found in a foetus
HbF
iron transportation etc
Liver secretes apotransferrin into the bile, which flows through the bile duct into the duodenum, where it enters the duodenal circulation:
The intestinal cells secrete free iron into the duodenal circulation.
The apotrasferrin binds with the free iron forming transferrin.
The iron is loosely bound in the transferrin and, consequently, can be released to any tissue cell at any point in the body.
Transferrin is then transported to the liver or the bone marrow:
Liver: here it enters the hepatocytes and combines with apoferritin, forming ferritin (storage molecule).
Bone Marrow: here it binds to receptors on the erythroblasts, delivering iron to the mitochondria for the production of haemoglobin.
