2: RBC and Anaemia Flashcards
Covers RBC, Blood transfusion, Blood cell diseases, Blood groups and Anaemia (168 cards)
1
Q
Where do blood cells originate from
A
Bone marrow:
pelvis, sternum, femur
- constantly regenerated -
2
Q
Where are RBCs derived from
A
Pluripotent haemopoietic stem cells (HSC)
3
Q
What 2 stem cells do HCSs give rise to
A
- lymphoid —> lymphocytes
- myeloid —> erythrocytes, platelets, granulocytes, monocytes, eosinophils, mast cells, basophils
4
Q
Haemopoiesis is the…
A
Formation and development of blood cells
5
Q
Life span and function of erythrocytes
A
120 days - due to lack of organelles
Oxygen transport
6
Q
Life span and function of platelets
A
10 days
Haemostasis
7
Q
Life span and function of monocytes
A
Several days
Phagocytosis, kill microorganisms
8
Q
Life span and function of neutrophils
A
7-10h
Phagocytosis, kill microorganisms
9
Q
Life span and function of eosinophils
A
shorter than neutrophil
Defend against parasites
10
Q
Life span and function of lymphocytes
A
Variable
Humoral and cellular immunity
11
Q
2 characteristics of HSCs
A
- Self renewal (some daughter cells remain as HSCs, pool not depleted)
- Differentiate and mature progeny (other daughter cells follow differentiation pathway)
allow expansion of cells to maintain adequate population of mature cells
12
Q
3 sites of haemopoiesis
A
- yolk sac (mesoderm of embryo) : 3wks
- liver ( HSC maintenance and expansion) : 6-8wks gestation - principle source of blood prior to birth
- bone marrow —> pelvis, femur, sternum, vertebrae (adults) , all bones (children) : 10wks gestation
13
Q
4 things controlling Haemopoiesis
A
- genes
- transcript factors
- growth factors
- microenvironment
14
Q
Where are HSCs and progenitor cells located
A
- ordered fashion in bone marrow
- amongst mesenchymal cells, endothelial cells
- interact with vasculature
15
Q
Disruption of Haemopoiesis regulation
A
Disturbs balance between proliferation and differentiation—> leukaemia or BM failure
16
Q
Glycoprotein hormones regulate
A
- proliferation and differentiation of HSCs
- function of mature blood cells
17
Q
Growth factors affecting erythropoiesis
A
Erythropoietin - glycoprotein hormone
18
Q
Growth factors affecting granulocyte and monocyte production
A
G-CSF
G-M
CSF
cytokines e.g interleukins
19
Q
Growth factors affecting megakaryocytopiesis and platelet production
A
Thrombopoietin (TPO)
20
Q
What can the common myeloid progenitor give rise to
A
Proerythroblast
21
Q
What do proerythroblasts give rise to
A
Erythroblasts —> erythrocytes (differentiation progresses, self renewal and lineage plasticity decrease)
22
Q
Reticulocytes are
A
Slightly immature RBCS
23
Q
Methylene blue stains
A
RNA content ( more in immature RBCs)
24
Q
4 things required for erythropoiesis
A
- iron
- folate
- Vit B12
- Erythropoietin EPO
25
Low iron / B12 / folic acid can lead to
Anaemia (reduced haemoglobin)
26
Macrocytic Anaemia
(RBCs large size)
- Due to B12/folic acid deficiency
- cells grow but don’t develop
27
Causes of microcytic Anaemia (paler and smaller RBCs)
-incr. blood loss
-reduced iron intake
28
Characteristics of Erythropoietin growth factor
- glycoprotein synthesised by kidney cells in response to hypoxia (supply-demand feedback loop)
- stimulates bone marrow to produce more RBCs
29
2 functions of Iron
- O2 transport via Hb
- needed in mitochondrial proteins :
Cytochromes a,b,c, for ATP prod.
Cytochrome P450 for hydroxylation reactions - ETC
30
Haem iron
Fe2+ - best absorbed form
31
Non-haem iron
Fe3+
best form in food
Requires reducing substances for absorption
32
Iron excretion
- no physiological mechanism by which iron is excreted by
- iron absorption is tightly controlled 1-2mg a day from diet
33
2 things B12 and folate are required for
-DNA synthesis - dTTP synthesis—> thymidine
-integrity of nervous system
34
B12 and folate deficiency affects:
All rapidly dividing cells:
- bone marrow: megaloblastic erythropoiesis
-epithelial surface of mouth and gut
-gonads
35
Where is folate absorbed
Small intestine: duodenum and jejunum
36
Where is B12 absorbed
- stomach : cleaved by HCL, combines with IF made in gastric parietal cells
- small intestine : B12-IF binds to receptors in ileum
37
B12 deficiency may result from:
-inadequate intake e.g. veganism
-inadequate secretion of IF : pernicious anaemia
-malabsorption e.g coeliac disease
-lack of stomach acid
38
RBC destruction
-Breakdown in spleen: old or abnormal
- globin returns to amino acids
- haem broken down into iron and bilirubin
-Fe: recycled to bone marrow - transported by transferrin in blood
-bilirubin: excreted in bile (Liver)
-destroyed by splenic macrophages
39
What does erythrocytes function depend on (3)
- integrity of membrane
- haemoglobin structure and function
- cellular metabolism
(Defects result in haemolysis)
40
Erythrocyte membrane structure
- biconcave shape - aids manoeuvrability through small vessels
- lipid bilayer membrane —> protein cytoskeleton cont. transmembrane proteins (maintain integrity, shape and elasticity of red cell)
41
Spheroctyes are
Cells approximately spherical in shape (lost area of cell membrane)
42
Structure of spherocytes
- round, regular outline
- lack central pallor
- less flexible so removed prematurely by spleen
43
How do spherocytes arise
Loss of cell membrane without loss of equivalent amount of cytoplasm so cell forced to round up
44
What is hereditary spherocytosis caused by
Disruption of vertical linkages in membrane
(Autosomal dominant)
45
When can elliptocytes (pencil cells) occur
In iron deficiency
46
2 Skeletal proteins found in RBC membrane
- Spectrin
- junctional
47
2 transmembrane proteins found in RBC membrane
- Band 3
- rhesus
48
How does deficiency in G6PD affect red cells?
1. G6PD is an important enzyme in HMP shunt
2. The HMP shunt involved in metabolism of glutathione protecting the red cell from oxidant damage
3. Therefore deficiency of G6PD causes red cells to be vulnerable to oxidant damage
49
What protects the red cells from oxidant damage?
Glutathione
50
What does G6PD deficiency cause?
Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
51
What are episodes of intravascular haemolysis associated with the appearance of?
considerable numbers of Irregularly contracted cells/ 'bite cells'
52
Blood is composed of
55% plasma
45% erythrocytes
53
Serum is
plasma without clotting factors
54
3 adaptations of RBCs
Incr. SA for gas exchange - biconcave shape
lack of organelles to allow maximum Hb
Incr. flexibility to move through narrow vessels
55
Haematocrit (HCT)
expresses ratio of RBCs to blood volume
- decimal or percentage
- values depend on age and sex
56
2 functions of HSC
self renew to replenish pool
differentiate into mature blood cells
57
What is RBC maturation guided by
Haematopoetic growth factors
58
Process of HSC differentiation to make erythrocytes
HSC
Common myeloid progenitor
Proerythroblast
Reticulocytes - appear blue, found in circulation
Erythrocytes
- as differentiation progresses, self renewal and lineage plasticity decrease
59
When and where is EPO produced
By the kidneys in response to hypoxia (low oxygen)
60
What is the difference between Folate and Folic acid
Folate = Vit. B9
Folic acid = synthetically derived Vit. B9 (not from food)
61
Function of Hepcidin
Hormone regulating absorption of iron in gut according to iron body stores
Produced at liver
62
Hypersplenism
overactive spleen
can lead to anaemia
63
Splenic sequestration
sudden pooling of blood in the spleen
- can be seen in anaemia
64
Splenomegaly
enlargement of the spleen
65
Anaemia is
a blood disorder defined as a reduction in Hb conc.
66
4 causes of reduced Hb concentration
Impaired red cell production
Loss of red blood cells - bleeding
Increased red cell destruction
Reduced red cell survival
67
Clincal presentations of anaemia
Reduced HB conc. --- poor oxygenation of tissues
-dyspnoea on exertion and rest
-pallor
-fatigue
68
2 clinical tests required for diagnosing haematological conditions
blood film and FBC
69
Differentiating anaemia types
Based on cell size and colour
Size (MCV or compare to lymphocytes) - normocytic, microcytic, macrocytic
Colour - Normochromic, Hypochromic (paler), Polychromatic (blue tinge)
Shape - normal, abnormal, immature
70
Microcytic anaemia
usually hypochromic
due to defects in haemoglobin synthesis
- iron deficiency anaemia (haem synthesis)
- thalassemias (globin synthesis)
- anaemia of chronic disease
71
Normocytic anaemia
cells of normal size
acute haemorrhage - loss of RBCs
72
Macrocytic anaemia
Subclassified as megaloblatic anaemia or non megaloblastic
73
3 causes of Non megaloblastic anaemia (Macrocytic)
liver disease and ethanol toxicity
haemolysis/polychromasia
pregnancy
74
Normal shaped RBCs on a blood film
central white spot -less Hb in depression
1/3 diameter should be pale
if greater proportion - hypochromic RBC
75
6 shapes of immature RBCs
Megaloblast
Reticulocyte
Sickle cell
Target cell
Poikilocyte
Elliptocyte
76
Poikilocytes are
RBC showing more shape variety than usual
77
Management of anaemia
dependent on cause
blood transfusion of packed red cells to quickly increase O2 carrying capacity of blood
78
3 causes of anaemia
Bleeding
Nutrient deficiency
Genetic causes
79
3 causes of iron deficiency
Inadequate intake
Inadequate absorption
Excessive iron loss by gradual prolonged bleeding
MICROCYTIC ANAEMIA
80
B12 and Folate deficiency usually lead to
Megaloblastic anaemia (macrocytic)
- larger RBC precursors released into circulation
- hypersegmented neutrophils
81
2 types of anaemia resulting from acute haemorrhage
normocytic
normochromic anaemia
- as no pathology in RBC synthesis (yet)
82
what anaemia results from gradual and prolonged bleeding?
(microcytic) iron deficiency anaemia
- commonly caused by excessive menstrual bleeding
83
How can genetic disorders cause anaemia
-structural abnormality in RBC leading to premature destruction by spleen and haemolytic anaemia
84
2 genetically controlled anaemias
Hereditary spherocytosis - vertical linkages disrupted
Hereditary elliptocytosis - horizontal linkages disrupted
- both autosomal dominant traits that disrupt proteins in RBC membrane
85
Thalassemias
genetic condition causing (microcytic) anaemia
- defect in alpha or beta globin chain (named subsequently)
- can be major or minor
86
Sickle cell anaemia
autosomal recessive (HbS)
defect in Hb synthesis affecting B-chain
removed by spleen
prone to occlusion
(HbAS -sickle cell trait)
87
What is classification of blood based on
- controlled by same gene or set of homolygous genes
- significance depends on ability of antibodies against the antigen to cause haemolysis
88
2 most significantly blood group systems
ABO system
Rh system
89
Blood group system
combination of antigens on RBC surface
90
Antigen classification in ABO system
Group A - antigen A
Group B- antigen B
(A and B are co-dominant)
Group AB- both antigen A and B
Group O - neither antigen A or B - recessive
91
Antigen classification in Rh system
Antigen D- recessive
RhD positive (dd) - expressed
RhD negative (Dd, DD) - not expressed
92
Type of antibody in ABO System
Pentametric IgM
93
Type of antibody in Rhesus system
IgG
94
Occurence of antibody in ABO system
naturally occuring
95
Occurence of antibody in Rhesus system
Acquired following exposure
96
How are ABO antibodies naturally acquired
Early life exposure to sugars which mimic A/B antigens on RBC surface
body develops Anti-A or B against antigen not expressed by own RBC
Antibodies exist in small quantities in plasma
97
How are Anti-RhD antibodies acquired following exposure to RhD antigen
antibodies only develop following exposure to RhD antigen (alloimmunisation)
98
Two types of haemolysis
HTR - Haemolytic transfusion reaction
HDFN - Haemolytic disease of the foetus and newborn
99
In a HTR
-incompatible RBCs transfused into patient
patient has antibodies against antigens on transfused cells leading to haemolysis of transfused cells
100
Response of Anti A and Anti B to a HTR
Activate complement
cause severe intravascular haemolysis (acute HTR)
can be fatal
101
Response of Anti-D to a HTR
can cause haemolysis mainly extravascular and HTR is delayed
not usually fatal
102
In HDFN
Foetal blood cells (RhD+) cross placenta and encounter mothers D antigen
mother produced Anti-D antigen in response (alloimmunisation)
Anti-D IgG crosses placenta and can haemolyse foetal blood cells
103
2 risk factors of HDFN
RhD - only IgG can cross placenta
Mother and newborn have incompatible blood
greater risk if :
mother is blood group AB
high titre of IgG
104
What needs to happen prior to a blood transfusion
Group and screen
O- blood given in emergencies
105
what does a group determine
ABO group - forward (patients RBC+anti-ABO antibodies) and reverse group (patients plasma+RBC expressing antigen A and B)
RhD status - test patients RBCs with anti-D antibodies
106
what does agglutation confirm
interaction between antigen and antibody and therefore presence of antigen on patients RBC
107
What does a blood screen entail
Patients serum tested against panels of RBCs that express relevant RBC antigens
To check for presence of acquired alloantibodies in blood
108
What are acquired antibodies formed as a result of
active immunisation to non-self RBC antigens following exposure to RBCs from another individual :
pregnancy - foetal RBC antigen enters mothers circulation
incompatible transfusion
109
Following a group and screen a Cross match is carried out this, includes
Patients plasma + RBC sample from donor
agglutation = incompatible
no change = compatible
110
How can blood be collected
Whole donation or apheresis
in apheresis blood donor connected to machine which separates out specific blood components
111
FFP is
Fresh Frozen Plasma
- contains all coagulation factors
-used in treatment of bleeding in patients with coagulopathies
112
Cyroprecipitate contains
fibrinogen
Factor VIII
von Willebrand factor
Factor XIII
113
Packed red cells are given to
increase Hb and oxygen carrying capacity of blood:
anaemia
haemorrhage
114
Shelf life and storage of packed red cells
35 days
in fridge at 4°C
115
How to know if a patient has responded to a red cell transfusion
Check for response clinically by assessing patient
measure Hb levels to check increase to normal range
116
Platelets are
fragments of megakaryocytes
117
Role of platelets
blood clotting
118
How are platelets produced for transfusion
pooling from whole blood donations or by apheresis
119
why may platelets be transfused
treat or reduce risk of bleeding
120
Why is it preferred that platelets match the patients ABO group
- can express ABO antigens (only in 4-7% of individuals)
- suspended in plasma which contains donors Anti-ABO antibodies (only a concern if sample in high-titre positive)
121
Platelet shelf life and storage
7 days
at room temperature, requires constant agitation to ensure continuous oxygenation
122
What does seeing nucleated RBCs in blood signify
high demand for RBCs so immature ones released prematurely into circulation
- nucleus lost as they mature
123
Why do polychromatic (immature RBCs) appear blue
high RNA content - shown on methylene blue stain
still reticulocytes that lose ribosomes after few days
124
Where is EPO made
kidneys
in response to hypoxia and anaemia providing a demand-supply feedback loop
125
How does EPO work
interacts with EPO receptors on RBC progenitors in bone marrow to increase RBC production
126
what foods can reduce iron absorption
soya beans - contain phytates that bind to iron reducing absorption
but also have iron in them
127
Negative feedback system involving Hepcidin
Erythropoietic activity supresses hepcidin synthesis, increasing ferroportin duodenum enterocyte, which increases iron absorption
128
Hepcidin in inflammation
Inflammation increases hepcidin which reduces iron supply leading to anaemia of chronic disease
-transferrin reduced
-ferritin increased
-gut iron absorption reduced
129
requirements for folate increase
pregnancy
increased RBC production - sickle cell anaemia
130
What 3 things does erythrocyte function depend on
Membrane integrity
Haemoglobin structure and function
Cellular metabolism
131
RBC membranes
lipid bilayer
supported by protein cytoskeleton with transmembrane proteins to maintain integrity, shape and elasticity
132
Haemoglobin structure
4 haem groups
each with Fe2+ bound by a porphyrin ring
Fe2+ can bind 1 O2 molecule reversibly
each haem group combined to a globin chain produced by cluster genes
133
Types of haemoglobin found in adults and foetuses
HbA - adults
HbB - foetuses
134
Right shift of haemoglobin curve
more O2 unloading
135
2 causes of Right shift
Bohr Effect
HbS - sickle cell haemoglobin
136
Left shift of haemoglobin curve
more O2 loading
137
2 causes of Left shift
Myoglobin
HbF - foetal haemoglobin
138
RBC metabolism and PPP
G6P is oxidised to CO2 producing NADPH - this is the Pentose phosphate pathway
G6PD is the rate-limiting enzyme in this pathway
NADPH reduces oxidised glutathione into reduced glutathione - antioxidant in RBCs
139
When are oxidants produced in the blood
During infection
exogenous e.g drugs/broad beans
140
Issues of G6PD deficiency
Intermittent severe intravascular haemolysis from oxidant damage
- irregular contracted, small bite cells with no central pallor
- Hb denatured and forms round inclusions:
Heinz bodies
X-linked recessive = usually homozygous males
141
Why is G6PD deficient present in individuals with malaria
Acquired immune response in order to combat malaria
better survival advantage as RBCs containing malaria removed
142
What are antioxidants
Chemicals protecting RBC from oxidants
143
Polycythaemia is
too many RBC in circulation
144
Two types of Polycythaemia
Pseudo
True
145
In pseudo polycythaemia
Reduced plasma volume
146
4 branches of true polycythaemia
Blood doping or over transfusion - cyclists
Appropriately increased EPO - high altitude place
Inappropriate EPO synthesis or use - cyclists or renal tumour
Independent of EPO - polycythaemia vera
147
What is Polycythaemia vera
myeloproliferative disorder of bone marrow
-drugs can be given to reduce bone marrow production of RBCs
- can cause hyperviscosity -- thrombosis-- requiring venesection
148
MCV is
average volume of each RBC
MCV (L) = Hct(L/L) x1000 / RBC x (10^12/L)
149
MCH is
mean cell haemoglobin
average mass of Hb in each RBC
MCH (g) = Hb (g/L) / RBC x (10^12/L)
150
MCHC is
mean cell haemoglobin concentration
average conc. of Hb in each RBC
MCHC (g/L) = Hb(g/L) / Hct (L/L)
151
2 mechanisms of anaemia
Failiure to produce RBCs
Excess RBC loss or destructuion
152
What is koilonychia and when does it occur
spooning of nails
presentation of anaemia
153
What is angular cheilitis and when does this occur
Inflammation of corners of mouth
presentation of anaemia
154
What is landsteiners law
Antigens present on RBC are opposite type to antibodies present in plasma
155
what antibodies and antigens are present in individuals with blood group AB
A AND B antigens in blood
no antibodies in plasma
156
what antibodies and antigens are present in individuals with blood group O
no antigens in blood
A and B antibodies in plasma
157
How do genes code for ABO
sugar residue is added to a common glycoprotein and fucose stem (H antigen) on RBC membrane
158
How do genes code for O blood
O gene is recessive - neither A or B sugars only H stem
159
How do genes code for A blood
A gene codes for enzyme adding N-acetyl galactosamine to common H antigen
160
How do genes code for B blood
B gene codes for enzyme that adds galactose to common H antigen
161
What patients are given RBCs
anaemia
162
Why are patients are given FFP
to treat
prolonged APTT and PT
or reversal of warfarin
163
Why are patients are given Cryoprecipitate
Replace FVIII and fibrinogen esp in heavy bleeding - also cont. VWF and FXIII
164
Why are patients given platelets
to treat :
Bone marrow failure
thrombocytopenia
massive bleeding / DIC
165
Why are patients given Factors VIII and IX
To treat :
haemophilia ( A and B - respectively)
166
Why are patients given immunogolbulins
to protect against Hep A
167
What are the main fluid compartments
Intracellular - 55%
Extracellular - 45%
(36% interstitial fluid
Transcellular fluid - 2%
Blood plasma - 7% )
of body water
168
Difference in plasma and serum use
plasma - easy to prepare
serum - blood into tube with anticoagulant, allowed to clot then centrifuged, cleaner sample (serum separator tubes have silica coating to induce clotting and gel layer to form physical barrier between cells and serum)
