Blood Flashcards
Blood makes up what compsotion of ECF ?
25%
What are are the 2 componenents of blood ?
cellular elements
plasma
What is the difference between ISF and plasma ?
plasma contains proteins
What does the plasma contain ?
Gases trace elements organic molecules ion water
What are the organic molecules that plasma can contain ?
Amino acids glucose proteins lipid nitrogenous waste
What are the 4 main plasma proteins ?
albumins
globulins
fibronogens
transferrin
Where are the plasma proteins produced ?
liver
What is albumin ?
the most abundant plasma protein
major contributors to colloid osmotic pressure
carriers of various substances
What are globulins ?
clotting factors
enzymes
antibodies
carriers
What are fibrinogens ?
form fibrin threads that are essential to blood clotting
What is transferrin ?
iron transport
globulins from the lymphoid tissue provide globulins
What are the cellular elements of plasma ?
erythrocytes
leukocytes
platelets
What do erythrocytes do ?
Transport oxygen from the lungs to the tissues
transport carbon dioxide from the tissues to the lungs
What do leukocytes do ?
involved in the immune reponse
work in tissues rather than the CS
What are thrombocytes ?
They are cell fragments that have split off a megakaryocyte
What are the types of leukocytes
neutrophils eosinophils basophils monocytes lymphocytes
What is a haematocrit ?
ratio of red blood cells to plasma
expressed as a percentage
How is a haematocrit made ?
drawing a blood sample into a capillary tube
placing it into a centrifuge
red blood cells go to the bottom
thin buffy coat in the top - leukocytes
What is the PCV ?
total percentage of red blood cells in the total volume of the blood
What can a low PCV indicate ?
anaemia
over production of WBCs
blood loss
What can a high PCV indicate ?
dehydration
What are the 2 ways of carrying out blood doping ?
PCV transfusion where the plasma and buffy coat are removed and only the red blood cells are injected back in
Injections of erythropoietin - stimulate red blood cell synthesis
What can serum be used to test for ?
blood type
cholesterol type
How can we obtain a serum sample ?
removing the anti coagulant from the blood and the serum separates
What is serum ?
clear liquid that can be separated from clotted blood
it lacks cells and clotting factors that are in the plasma
What does the serum contain ?
antigens
antibodies
hormones
drugs
What are the properties of plasma ?
high specific heat capacity to move metabolised heat and maintain body temperature
over 90% water - transport molecules and materials
What is the most abundant cation in the plasma ?
sodium
What is the most abundant anion in the plasma ?
chloride
What is hyponatraemia ?
salt concentrations are diluted
osmolarity of plasma reduces
fluid will move across the blood brain barrier leading to swelling
What molecules are transported in the plasma ?
nutrients - glucose , aminoa acids , lipids and vitamins
waste products - creatinine , billirubin and urea
dissolved gases
Hormones - peptides and steroid hormones
Where is oncotic pressure higher ?
in the plasma than the ISF
What is oodema ?
obstruction/removal of lymph nodes
proteins move from plasma to ISF less colloid osmotic pressure and less opposition to hydrostatic pressure
excess fluid in the interstitial space.
What does an increase in capillary hydrostatic pressure do ?
increase in venous pressure heart failure right ventricle fails build up of blood that is pushed back into the venous system swelling
What does a decrease in plasma protein concentration mean ?
due to liver failure
oncotic pressure not maintained
fluid not drawn back
What does an increase in interstitial proteins mean?
inflammation
histamine produced
leaky capillaries
proteins move out of plasma
What happens if arterial blood pressure falls ?
capillary hydrostatic pressure falls too
increase in fluid absorption
net absorption - maintain blood volume and therefore pressure
What is haemopoiesis ?
process by which blood cells and platelets are formed
What an pluripotent haematopoietic stem cells do ?
develop into any blood cell type
Where does haemopoiesis occur ?
initially in the yolk sac
as the embryo develops blood cell production spreads to liver , spleen and bone bone marrow
What are the remaining regions of active bone marrow as humans age ?
pelvis
spine
cranium
ribs
Why is active bone marrow red ?
contains haemoglobin
What colour is inactive bone marrow and why ?
yellow
adipocytes
What are the 2 lineages blood cells can be produced in ?
myeloid line
lymphoid line
What are the 2 classifications of leukocytes ?
phagocytes
granulocytes
What do monocytes become in tissues ?
macrophages
What can basophils become in tissues ?
mast cells
What are the phagocytes ?
lymphocytes
monocytes
neutrophils
What are granulocytes ?
neutrophils
eosinophils
basophils
however they can have phagocytic properties
Where does an erythroblast loose its nucleus ?
bone marrow
What do reticulocytes loose ?
their mitochindria
How do megakaryocytes become platelets ?
the megakaryocytes loose their protrusions and become platelets
What are the proportions of blood cells made by bone marrow ?
25% red blood cells
75% white blood cells
Which cells have the shorter lifespan ?
white blood cells
What is the half life of neutrophils ?
6 hours
How long can a RBC survive in circulation ?
4 months
Which molecules can stimulate haematopoiesis ?
cytokines colony stimulating factors interleukins erythropoietin thrombopoietin
What are cytokines ?
proteins that are released from a cell and stimulate growth and activity of another cell
What are colony stimulating factors ?
they are used in colony forming units
made by endothelial cells and WBCs
What is erythropoietin ?
a glycoprotein
controls red blood cell synthesis
What is thrombopoietin ?
produced in the liver cells
influences megakaryocytes
What are interleukins ?
secreted by WBCs
stimulate production of the same WBC in the immune response
mobilise haematopoietic stem cells
What does eryhtropoietin do ?
stimulates red blood cell production
released in times of hypoxia
increases RBCs and therefore haemoglobin allowing more o2 transport
What is released to produce EPO ?
HIF-1
a transcription factor
What is differentiation ?
the process by which a PHSC becomes increasingly committed to a particular cell type
Which molecules work during erythropoiesis ?
EPO IL-3
What is the process by which erythrocytes are formed ?
proerythroblast
erythroblast pinches off nucleus
reticuclocytes loose mitochondria (blood)
erythrocytes
What is the rate at which bone marrow generates new RBCs ?
2-3 million per second
How do red blood cells die ?
they live for 120 days
swell up
rigind and fragile
How are dead RBCs removed ?
tight network of vessels in spleen and liver
How is hypoxia detected ?
by the peritubular cells of the kidney
What do the peritubular cells do ?
release EPO
What does EPO do ?
increase stem cell turnover
maturation of RBC precursors
increase rate of RBC release
How long does it take for new RBCs to appear ?
1-3 days
What happens if there is excess HPO ?
immature red blood cells bind to the HPO
mop up the excess
What is thrombopoietin ?
a glycoprotein
regulates growth and maturation of megakaryocytes
Where is thrombopoietin produced ?
primarily in the lier and the kidney
How do platelets regulate the amount of TPO ?
platelets bind to TPO and destroy the excess TPo in negative feedback
What is leukopoiesis ?
stimulation and generation of leukocytes
What do CSFs do to leukocytes ?
they stimulate growth of leukocyte colonies
What makes CSFs ?
endothelial cells
bone marrow
fibroblasts
WBCs
What are inhibitory factors of leukopoiesis ?
hormones
antibiotics
alcohol
What are granulocytes ?
contain granules
neutrophils
basophils
eosinophils
Which cells are agranulocytes ?
monocytes
In a bacterial infection which cells will be abundant ?
WBCs
neutrophils and monocytes as they are phagocytic
In a viral infection which cells will be abundant ?
increased lymphocytes as they have memory cells
What is granulopoiesis ?
development of granulocytic white blood cells
neutrophils
eosinophils
basophils
What are the stages of granulopoiesis ?
myeloblasts
these enlarge and differentiate into
promyelocyte
What are neutrophils ?
most abundant leukocyte
granules contain lysozymal enzymes
multilobular nucleus
What are eosinophils ?
fight parasites and viruses in allergic reactions
they appear red
What do eosinophilic granules contain ?
Major basic protein
Are eosinophilic granules basic or acidic ?
basic - stain with Eosin which is acidic
What are basophils and what do they contain ?
histamine , heparin and peroxidases
used in allergic reactions
Are basophilic granules acidic or basic ?
they are acidic
they stain with haematoxylin dues which are basic
appears blue
What is major basic protein ?
predominant constituent of the crystalline core of eosinophilic granules
toxic in bacteria
What are macrophages ?
they are formed from monocytes
they are agranulocytes
they have a slightly indented nucleus
Which molecules are involved in monopoiesis ?
CSFs
interleukins
What are the steps in monopoiesis ?
monoblast
promonocyte (slightly indented nucleus)
mature monocytes
mature monocytes migrate from the bone marrow to the peripheral tissue and become macrophages
What do macrophages do ?
phagocytose pathogens and debris
they act as APCs to lymphocytes
How are lymphocytes made ?
along thelymphoid line
made from a common lymphoid precursor which can develop into a pro T cell or a pro B cell
How can lymphocytes be identified ?
large nuclei
they are agranulocytes
What are CD molecules ?
molecules on the surface that are used to differentiate and purify specific cells
How many CD molecules are there ?
300
What can antibodies do ?
can detect different molecules on WBCs and RBCs
What can uncommitted stem cells do ?
differentiate into a range of cells
What are sources of blood cells ?
bone marrow
peripheral blood (if cytokines are injected)
umbilical chord blood
Why might a bone marrow transplant be needed ?
if an individuals stem cells are effected
must be matched by HLA
What is non hodgkins lymphoma ?
cancers that develop in the lymphatic system
What is leukaemia ?
cancer of leukocytes and bone marrow
leukocytes replicate in an uncontrolled manner
What are the 2 types of leukaemias ?
acute and chronic
What is acute leukaemia ?
bone marrow releases masses of immature WBCs
What is chronic leukaemia ?
bone marrow releases relatively mature but ineffective WBCs
What can leukaemia affect ?
lymphoblastic (lymphoid line)
myelogenous (myeloid line)
What happens to the nucleus when erythroblasts pinch off it in erythropiesis ?
it is phagocytosed by phagocytes
What is the shape of erythrocytes ?
biconcave disc shape
What does the shape of the erythrocyte allow for ?
larger surface area
thin - rapid diffusion of oxygen
flexibility - squeeze through narrow capillaries
How do RBCs get their energy ?
ATP from glycolysis (they have no mitochondria)
What is the protein in a RBC ?
haemoglobin
What is a molecule of haemoglobin made from ?
2 molecules of alpha globin
2 molecules of beta globin
The 2 chains are different sizes , what does this allow for ?
they can fit together to make a tetramer
What does oxygen bind to in a haemoglobin molecule ?
one of the 4 globin chains
What ave rise to the alpha globin and beta globin families ?
a gene duplication
What does foetal Hb contain and why ?
gamma globin
higher affinity for oxygen
Why are the alpha and beta globin genes separated ?
Beta globin genes are in chromosome 11 chromosome breakage is believed to have separate the genes so that the alpha gene is on chromosome 16
How many haem groups are there per Hb molecule ?
4
What is a haem group made of ?
carbon-nitrogen-hydrogen porphyrin ring
What do the haem groups attach to in Hb ?
each haem group is tightly bound but non covalently bound to one of the 4 lobin chains
What happens to iron after it is ingested from the diet?
it binds to transferrin
What happens to excess iron ?
it is stored in the liver as ferritin
Where is haemoglobin made ?
in the bone marrow
How long does a RBC live for ?
120 days
How far does a RBC travel ?
1000 km
What happens to old RBCs ?
they are destroyed by the spleen and the Hb is converted to bilirubin
What happens to bilrubin ?
it is metabolised by the liver and excreted in bile
it is excreted by the kidney in urine
excreted in faeces
What is hyperbilirubinaemia ?
too much bilirubin in the blood
babies cannot break down the bilirubin so it builds up in tissues
presents as jaundice
What are the factors that determine Hb ability to carry oxygen ?
partial pressure of oxygen
number of free binding sites for oxygen in a RBC
Why is Hb nearly fully saturated in the lungs ?
there is a high enough partial pressure
What is the saturation in resting tissue and why ?
75 %
in resting tissue there is a high amount of c02 which means a lower Hb affinity for 02
the 02 is released
What happens during exercise ?
p02 falls
Hb will release 02
02 is used to generate ATP
What is the bohr effect ?
during anaerobic exercise there is a rise in lactic acid levels this reduces the affinity of Hb for O2 and 02 is released
What are the other molecules that Hb can bind to ?
Carbon dioxide protons carbon monoxide nitric oxide glucose
Which gas out competes oxygen for binding sites on haemoglobin ?
carbon monoxide
What are haemoglobinopathies ?
qualitative
mutations in globin genes
globin chains are abnormal
What is an example of a haemoglobinopathy ?
sickle cell anaemia
What are thalassaemias ?
quantitative
reduced amount/abnromal globin chains
due to defects at the gene expression level
What causes sickle cell anaemia ?
a mutation in the gene coding for B globin of Hb
What is the sickle cell trait ?
heterozygotes
rarely have symptoms
confers a benefit in that they are resistant to malaria as the parasite cannot hold onto the actin in erythrocytes
What happens to those who are homozygotes ?
develop sickle cell anaemia
HbS polymerises at low P02 - long crystals of HbS
crystals are lress soluble and form intracellular precipitates - sickle cell shaped erythrocytes
What is the consequence of having sickle shaped RBCs?
fragile and more likely to tear
tangled and blocked in vessels
What is alpha thalassaemia ?
production of alpha globin is deficient
excess beta chain production
unsable tetramers
What is beta thalassaemia ?
excess alpha chains produced
bind to RBC membranes
damage
toxic aggregates
What is anaemia ?
condition that arises from insufficient erythrocytes or insufficient Hb content
What is the main consequence of having anaemia ?
there is a reduction in the ability of RBC to oxygenate tissues leading to tissue hypoxia
What are the 3 absolute indices
MCV
MCH
MCHC
What is the MCV ?
mean corpuscular volume
average RBC volume
measured in Fl
What is MCH ?
mean corpuscular Hb content
average amount of Hb per RBC in pg
What is MCHC ?
mean corpuscular haemoglobin concentration
g/L g/100 ml
average conc of Hb inside a RBC
What are some features of anaemia ?
headaches
lethargy
shortness of breath
tachycardia
How can we classify anaemia ?
based on RBC size and Hb content
mode of development
If cells have a normal MCH and MCV they are ?
normocytic and normochromic
If cells are normochromic and normocytic why might someone present signs of anaemia ?
acute blood loss
haemolysis
marrow disease
if cells have a high MCV they are ?
macrocytic
Why might someone have macrocytic cells
vitamin b12 deficiency
If RBCs are small and pale they are ?
microcytic and hypochromic
What are microcytic and hypochromic cells associated with ?
iron deficiency anaemia
What are the signs of iron deficiency anaemia ?
hypochromic and microcytic RBCs
low MCV and ,MCH
How can er classify anaemia based on mode of development ?
acute/chronic haemorrhage - iron deficiency anaemia
failure to produce RBC - due to deficiency in the haematinics , marrow disease or leukaemia
Excess destruction - haemolytic anaemia , sickle cell or thalassaemia
What does leukaemia mean for the absolute indices ?
there is over production of WBC
leading to low PCV
What is acute haemorrhage ?
less than litre of blood lost
What can pumping with intravenous fluid cause ?
haemodilution
number of RBC decreases
normocytic and normochromic
blood contains reticulocytes - replace
What is a chronic haemorrhage ?
occur over time
can be GI related
presents as Fe deficiency
What are the haematinics ?
the vitamins and minerals needed for normal erythropoiesis
vitamin B12
folate
iron
What is ferritin ?
excess iron is stored in the liver as ferritin
normal range - 15-400
How much iron is in the body ?
3-5 g
Where is iron in the body found ?
75% in Hb in erythrocytes
20% in ferritin in the liver
5% in myoglobin
0.1% transferrin
What is myoglobin ?
a protein that contains a haem group
carries oxygen to the muscle
What is transferrin ?
protein that binds to iron and transports it throughout the body to the bone marrow usually
How is iron usually lost ?
sloughing of epithelial cells
How much iron is required to meet the daily requirement ?
10-20 mg per day
What percentage of iron consumed is absorbed ?
10%
What are the 2 types of iron in the food ?
haem iron and non haem iron
What is haem iron ?
found only in myoglobin in meat chicken and fish it is rapidly absorbed in the gut
What is non haem iron ?
found in plants
not easily absorbed by the body
What are the inhibitors if iron absorption ?
the bind to iron and prevent its absorption
eg, phytates , phosphates , tannins
What are promoters of iron absorption ?
vitamin C and citric acid
What are the 2 valency states of iron ?
Fe 2+ and Fe3+
What is ferrous haem iron ?
Fe 2+
What is non haem ferric iron ?
Fe3+
Which form of iron is absorbed ?
ferrous
How can Fe3+ be reduced ?
vitamin C and citric acid
Why might someone have iron malabsorption ?
high phytate diet
low Vit.C
citric acid
What is the avergae dietary intake of vitamin B12 ?
20 miligrams
What is the minimum intake of vitamin B12 ?
1-2 miligrams per day
What are sources of vitamin b12 ?
animal produce
marmite
How long can vitamin B12 stores last ?
several years
What is the average dietary intake of Folate ?
250 miligrams per day
What is the minimum intake of Folate ?
150 miligrams per day
What are sources of folate ?
liver and veg
How long do folate stores last ?
few months
What are folate and vit B12 needed for ?
DNA synthesis
What happens when vit.B12 and folate are deficient ?
ineffective DNA synthesis
delayed nuclear maturation
cytoplasmic maturation continues
cells have a large cytoplasm
What are the features of v.12 and folate deficient cells ?
asynchronous cells
large cytoplasm
megaloblastic
neutrophils have more lobes
What is the pathway of folate ?
folate dihydrofolate tetrahydrofolate 5,10 methylene 5-methyl FH4
What does methionine synthase do ?
it converts homocysteine into methionine
What does M.S require ?
vit.B12
to allow folate to be recycled
How is homocysteine converted to methionine ?
Homocysteine take carbon from 5-methyl FH4 to become methionine
What does the 5-methyl FH4 become ?
tetrahydrofolate
How is folate used in DNA synthesis ?
5,10 methylene FH4 donates carbon to dUMP
the 5,10 methylene FH4 becomes dihydrofolate
dUMP becomes dTMP which becomes DNA
What happens if there is no vitamin B12 ?
MS would not be activated
no recycling of folate from 5 methyl FH4 to tetrahydrofolate
no 5,10 methylene to donate carbon to dUMP
What is megaloblastic anaemia ?
deficiency in vit.B12 and folate
cells become megaloblastic
reduced survival time of cells
cant transport oxygen as well
What are the 2 main problems associated with vitamin B12 deficiency ?
megaloblastic anaemia as no recycling of folate
B12 is a coenzyme for fatty acid breakdown - abnormal cell membranes - spinal chord degeneration - neurological symptoms
What are the causes of vitamin B12 deficiency ?
dietary
GIT disease / surgery
pernicious anaemia
crohns disease
Which cells produce IF ?
parietal cells that line the wall of the stomach
What does IF do ?
binds to B12
helps b12 to travel through the tract
Where does if bind in the ileum ?
IF binds to mucosal cells receptors
allows receptor mediated endocytosis into the blood
What are the 2 binding sites on IF ?
one for b12
one for the receptor in ileum mucosal cells
What is pernicious anaemia ?
autoimmune response to IF producing cells
eg. the parietal cells
destroys IF and b12 cant be absorbed
What are the symptoms of pernicious anaemia ?
macrocytic cells
egg shaped
less biconcave
neutrophils are multilobular
Why is serum B12 low in pernicious anaemia ?
v12 deficiency means that folate is trapped as 5-methyl FH4
this is extracellular
What is the test for pernicious anaemia ?
schilling test
What isthe first part of the schilling test ?
a does of radioactively labelled B12 2 hours later large does of IM B12 this saturates b12 binding sites radio labelled b12 should pass in urine if less than 15% - malabsorption
What is the second test
large dose of B12 and IF
large B12 im Injection
more than 15% absorption - pernicious anaemia
less than 15% - ileal disease
Why can folate deficinect occur in a few months ?
small stones that can degrade over a few month
What are the causes of folate deficiency ?
decreased intake
increased requirement
malabsorption in GI disease
What can marrow disease cause ?
failure to produce RBCs
What is aplastic anaemia ?
bone marrow not functioning
pancytopoenia
die to autoimmune disease or genetic fanconi anaemia
What is spherocytosis ?
spectrin mutation abnormal RBC membrane
What is haemostasis ?
the process by which bleeding stops to keep blood within the vessel
What are the 3 mechanisms of haemostasis ?
vasoconstriction
formation of the platelet plug
blood coagulation to form the thrombus
What is vasoconstriction ?
applying pressure to an artery or arteriole to limit blood flow and stop bleeding
pressure must be applied to reduce blood flow to allow the creation if the seal
smooth muscle responds to paracrines - constricts reducing blood flow
How are thrombocytes formed ?
they are formed as the fragments off megakaryocytes
What regukates the number of thrombocytes ?
thrombopoietin
regulates the number of thrombocytes by a negative feedback loop
What destroys thrombocytes ?
spleen
What is the average lifespan of a thrombocytes ?
8-12 days
What do thrombocytes contain ?
basophilic intracellular granules
What initiates platelet adhesion ?
exposure to collagen
What is released on exposure to collagen and what does it do ?
vWF- released by the endothelium to make platelets sticky
What allows platelets to bind to collagen ?
integrin
How are platelets activated ?
when they bind to collagen
What do activated platelets release ?
intracellular granules
serotonin
ADP
platelet activating factor
What does serotonin do ?
aids in platelet aggregation
What does ADP do ?
aids in platelet aggregation
What does platelet activating factor do ?
activates more platelets
released by platelets , neutrophils , monocytes
What does release of granules cause and why ?
thromboxane 2
this is released from the platelet membrane and increases aggregation and vasoconstriction
How is the plug kept local ?
endothelium releases platelet activating factor to prevent the platelets binding to normal endothelium
also releases prostacyclin and nitric oxide
What is coagulation ?
the conversion of the platelet plug into a more stable thrombus
what is the overall reaction in coagulation ?
the conversion of soluble fibrinogen into insoluble fibrin
What is vitamin K needed for and what does it do ?
it is needed for the activation of clotting factors and to allow calcium to bind to the clotting proteins
What is the intrinsic pathway activated by ?
initiated by exposed collagen
this activates factor XII which is already in the blood
What initiates the extrinsic pathway ?
initiated by damaged tissue exposing thromboplastin (factor III)
this activates factor VII
factor III must be released so this is extrinsic
Describe the intrinsic pathway ?
collagen exposure activates factor XII XIIa activates XI XIa activates IX IXa activates X in the common pathway vWF activates VIII
Describe the extrinsic pathway ?
Damages tissue exposes factor III
factor III activates VII
VIIa activates X in the common pathway
Describe the common pothway ?
factor X is activated by the extrinsic and intrinsic pathways
Xa converts Prothrombin to thrombin via thromboplastin
Thrombin converts soluble fibrinogen into insoluble fibrin
Thrombin activates XIII which converts the insoluble fibrin into cross linked fibrin this is the clot
What is required for coagualtion ?
vitamin K
calcium ions
phospholipids
What does anticoagulation involve ?
stopping platelet adhesion
inhibiting the coagulation pathway
stopping fibrin production
What releases anticoagulants ?
endothelial cells
What are the anticoagulants ?
protein C
Heparin
Anti thrombin
thrombomodulin
What do heparin, anti thrombin and thrombomodulin do?
block thrombin
factors IX XI XII and X
What does protein C do ?
block V and VIII
When the clot is no longer required what is it broken down by ?
plasmin - a fibrinolytic agent
How is plasmin made ?
from plasminogen which is found in the clot
What catalyses the reaction from plasminogen to plasmin ?
thrombin
tissue plasminogen activator
Why is fibrinogen also broken down and why ?
to prevent it forming fibrin
What are the blood indices ?
PCV
RBC count
Hb conc
What is PCV/haematocrit ?
volume percentage of RBC s in blood
How is PCV determined ?
centrifuging a blood sample into the buffy coat , plasma and packed red blood cells
the volume of red blood cells is divided by the total volume
What is a normal PCV ?
35-54 %
What is red blood cell count ?
the number of red blood cells a person has
How is RBC count determined ?
placing cells in small squares
counting the number of cells
extrapolating this to find the number of blood cells
blood dilution factor
What is the unit of RBC count ?
million per microlitre
What is a normal red blood cell count ?
- 6-5.9 million per microlitre in males
4. 2-5.4 million per microlitre
What is haemoglibin concentration ?
average concentration of Hb in a red blood cell
How is Hb conc determined ?
Drabkins reaent added to blood sample
diluted
spectrometer used to measure the abosrption wavelength
compared to a graph
What are the units of haemoglobin conc ?
g/L
What is a normal Hb conc ?
13.5 to 17.5 g/L in males
What are the absolute indices ?
measurement of the size and Hb content of RBCs they are used in the diagnosis of anaemia
MCH
MCV
MCHC
What is MCH ?
mean corpuscular haemoglobin
average mass of Hb in a cell
How is MCH determined ?
mass of Hb per L of blood / number of RBC per L of blood
What are the units of MCH ?
pg
pico = 10 ^ -12`
What is MCHC ?
mean corpuscular haemoglobin concentration
average conc of Hb per red blood cell
How is MCHC determined ?
mass of Hb per 100 ml of blood / PCV in ml per 100 ml of blood
What is a normal ,MCH ?
27-32 pg
What are the units of MCHC ?
gg/L or g/100 ml
What is the normal range for MCHC ?
30-35 g/100 ml
What is MCV ?
mean corpuscular volume that a red blood occupies
How is MCV determined ?
volume in litres occupied by a RBC in a L / number of RBC per L
What is the unit of MCV ?
fl
femto = 10^-15
What is the normal MCV ?
83-96 fl
What are the absolute indices for iron deficienecy anaemia ?
MCV will be lower
MCH and MCHC also low
What are the absolute indices for Vitamin B112 and folate deficnency ?
megaloblastic anaemia - MCV high
MCH high and MCHC high due to lower RBC count
What are thromboembolic episodes ?
where the thrombus breaks loose and is carried in the blood stream to plug another vessel
Why can clots from ?
scarring
foreign surfaces
slow blood
What are pieces of the thrombus that break off called ?
emboli
What is deep vein thrombosis ?
blood clot usually develops inn a depp leg vein
causes pain and swelling
leads to pulmonary embolism - blood clot breaks off and blocks a vessel in the lung
What is disseminated intravascular coagulopathy ?
tissue damage leads to factor III release from the extrinsic pathway
this uses up all the molecules in the coagulation pathway
fibrin degradation products are released - bleed to death
How can artery blockage by a clot be removed in myocardial infarction ?
tissue plasminogen activator
How does aspirin work ?
prevents platelet plug formation by inhibiting an enzyme in the synthesis of thromboxane A2
How does warfarin work ?
blocks action of vitamin K - a cofactor needed in the activation of clotting factors
When taking a haematocrit why is calcium removed ?
it is removed by the chelator to prevent coagulation
What does ehlers danlos syndrome mean ?
collage disorder - platelet plug cant form as blood is not exposed to collagen
What is purpura ?
red/purple spots on the skin
a bacteria releases a toxin that that activates clotting factor XII
this causes disseminated intravascular coagulopathy
What is thrombocytopenia ?
low levels of thrombocytes
below 60 x 10^9 / dl
could be due to bone marrow suppression due to chemotherapy
What is thrombocythemia ?
excess platelet production
What is thrombopathy ?
platelets have defective thromboplastin (catalyses prothrombin to thrombin)
What is haemophilia ?
blood clotting factor is absent or defective
there is a normal vascular and haemostatic response but no clotting
What is haemophilia A ?
factor VIII deficiency
X-linked recessive
nornal bleeding time
affects intrinsic patway
What is haemophilia B ?
factor IX deficiency
X-linked recessive
What is haemophilia characterised by ?
spontaneous bleeding
What is von willebrand disease ?
most common inherited disorder vWF usually mediates factor VIII activation - therefore low levels of VIII and makes platelets sticky can lead to anaemia platelet count is normal
What is bleeding time ?
the time taken for the formation of the platelet plug against a pressure of 40 mm Hg
What is the normal bleeding time ?
3-8 mins
What can bleeding time be used for ?
vWF deficiency
thrombocytopenia - needed in the plug
Why is calcium removed ?
times are independent of calcium (needed in all 3 pathways)
What is prothrombin time ?
time taken fro the formation of fibrin in a high concentration of thromboplastin on recalcification
effectiveness of extrinsic and common pathway
What is normal prothrombin time ?
10-14 secs
What is thrombin time ?
the conversion of fibrinogen to fibrin is catalysed by thrombin . thrombin is added directly to the sample bypassing the extrinsic and intrinsic pathways
What is activated partial prothrombin time ?
intrinsic and common pathway effectiveness
issues with thrombin and fibrinogen
What is normal APPT ?
38-45 secs
What are the 2 types of immunity ?
innate and specific
What are the chracteristics of innate immunity ?
operates early in the immune response
identical and present in individuals all the time
quality/quantity is constant after exposure
no immunological memory
What are the characterisitics of specific acquired (adaptive) immunity ?
it is specific to non slef antiens
requires prior exposure
not immediate
immunoligcal memoey for the secondary immune rsponse
What are the physical and chemical examples of innate immunity ?
keratinised epithelium
mucus
ciliated epithelium
extreme local pH
How does mucus work ?
highly glycosylated protein
attracts water
stops particles spreading by sticking them together
Which phagocytic cells are involved in innate immunity ?
neutrophils
eosinophils
monocytes
What are the characteristics of neutrophils ?
multilobular nuclei
phagocytic
primary response
short lived and rapid turnover
What are the characteristics of eosinophils ?
granulocyte
allergic responses
larger than erythrocytes
What are the characteristics of monocytes ?
differentiate from macrophages in the tissues
signal innate and adaptive responses via cytokines n
scavenger cells for phagocytosis
why mght opsinisation be required ?
not all foreign particles are recognised by the immune system some might need to be antibody coated
this makes the pathogen more attractive to phagocytes
Where might opsinisation be important ?
in bacteria that have a capsule
What is the complement system ?
proteins that interact in the blood
the proteins are inactivated and become activated by different pathways
What can activated complement proteins do ?
carry out opsinisation - facilitating uptake and killing of pathogens
recruitment of inflammatory cells
perforation of the cell membrane can cause lysis
What is adaptive immunity mediated by ?
lymphocytes
What are the 2 types of adaptive immunity ?
humoral immunity - involves antibodies from a B cell lineage
Cellular immunity - activated T cells which can be cytotoxic or activate B cells
What are dendritic cells ?
they can signal for other T cells
they are APCs
What are mast cells ?
involved in alleries and the immune reponse as they release histmaine
How do lymphocytes appear ?
large nucleus and small cytoplasm
larger than erythrocytes
What are plasma cells ?
fully differentiated B cells
secrete antibodies
eccentric nucleus
extensive RER
What is an antibody ?
aqa secreted immunoglobulin that works in the mucosas , tissue and body fluids
WHhat is the structure of antibody ?
2 light chains
2 heavy chains
2 antigen binding sites
receptor binding sites
What are antibodies involved in ?
opsonisation
agglutination
neutralisation
activation of complement
What does the activation of complement lead to ?
plasma proteins that are activated by pathogens leading to a cascade of different reactions
What are monoclonal antibodies ?
they are clones of antibodies produced by the same B cell
highly specifc for an individual antigen
How can monoclonal antibodies be used therapeutically ?
herceptin in the treatment of breast cancer - only used if the HER2 receptor is present
infliximab used in rheumatoid arthritis - works against a TNF
What is a key step in adaptive immunity ?
presentation of an antigen to a T cell by an antigen presentingg cell
What is MHC ?
major histocompatibility complex
set of cell surface proteins essential for recognition of the immune system - they are p;aced on APC
What does an APC do ?
triggers T cells - activate cytotoxic T cells
activate B cells to produce antibodies
Which cells acts as APCs ?
dendritic cells and macrophages
What does it mean if MHC is highly polymorphic ?
more than 2 types
many different structures
specific combination is unique to the individual
MHC genes are analysed in tissue matching for transplantation
What are memory cells ?
long lived cells that are capable of responding to an antigen on its re introduction after initial exposure
What does immunological memory mean for the secondary response ?
in the secondary response antibody production is quicker and more substantial on the second exposure to the antigen
How does gingivitis progress ?
inflammation attracts neutrophils which are in large reserves in the bone marrow
neutrophils engulf and kill bacteria
neutrophils try to access bacteria and this leads to destruction of collagen
when they die in large numbers they are degraded by macrophages - swelling
What is the biochemical basis for the blood groups ?
a complex mixture of glycoproteins and glycolipids that are antigens in the surface of erythrocytes
What are the classifications of blood groups ?
ABO system
Rhesus factor presence or absence
What is the biochemical basis for the ABO systerm
ABO antigens are glycoproteins or glycolipids that consist of a ceremide (lipid) which has an oligosaccharide attached to it
How are the A/B/O groups characterisd ?
different enzymes that alter the glycoprotien in a different way
What are the enzymes responsible for modification ?
O - inactive glycosytransferase
A- A-Glycosytransferase
B- B- Glycosytransferase
What do the enzymes modify ?
Glycoprotein H
An individual develops blood group
antibodies to which antigens ?
the antigens it does not have present on its erythrocytes
What do ABO genes exhibit ?
co dominance - some alleles are both expressed in the phenotype eg. AB or BO
What is self tolerance ?
if antigens are already in the RBC surface - antibodies arent produced
What does serum contain ?
the antibodies to the antigens of blood groups the person doesnt express
Which antigens are present on someone of O blood type ?
none
Which antigens are present on AB ?
A and B antigens
When does agglutination occur ?
if the blood groups arent compatible
Which group is the universal donor ?
O - no antigens
Which group is the universal recipient ?
AB - no antibodies
What does agglutination lead to ?
a haemolytic transfusion reaction
RBC agglutination
intravascular coagulation
RBC lysis - antibodies binfd to RBCs activating complement - leads to anaemia
What is the recipient serum tested for ?
that there are no other antibodies against other antigens
What percentage of caucasians have the D antigen and are Rhesus postive ?>
85%
What happens in the first pregnancy of a rhesus positive baby and rhesus negative mother ?
the presence of the D antigen on foetal erythrocytes initiates the immune response from the mother
this is a primary response - minor destruction of foetal erythrocytes
What happens in the second and subsequent pregnancies of a rhesus positive baby and rhesus negative mother ?
the mother will initiate the secondary immune response - memory B cells are abundant
major destruction of foetal erythrocytes - babies are anaemic
What can be given to overcome haemolytic disease of the new born ?
mothers can be given transfusions of antibodies against the rhesus antigen - stops the rhesus antigen on foetal erythrocytes being recognised by the mother immune system
What are the 3 modes of developing anaemia ?
failure to produce
excess destruction
acute/chronic haemorrhage
What is haem iron ?
fe 2+
ferrous
What are examples of innate immunity ?
Ciliated epithelium
Mucosa
keratinised epithelium
localised ph
What are the roles of macrophages ?
scavenger cells
signal for innate and aquired immunity via cytokines
What aer the actions that activated complement can carry out ?
opsinisation
perdoration of pathogen cell membranes
recruitement of inflammotry cells
What are dendritic cells?
signal fro t cell s
APCs
What are mast cells ?
in allergic reactions
produce histamine
inflammatory response
What are the 4 roles of antiibodies ?
opsinisation
neutralisation
activaation of complement
agglutination
