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Chapter 2
Table of Contents
Chapter 2......................................................................................................................0
Pathology of Red Blood Cells.....................................................................................0
Table of Contents........................................................................................................1
1. Deficiency of RBCs/Hb: Anaemia [1-4]..............................................................2
a)
b)
Reduction of the total circulating red cell mass below normal limits
decreasing the oxygen-carrying capacity of the blood
Epidemiology of anaemia:
o 10% in developed countries
o 25-50% in developing countries
o Of this iron deficiency most common
1.1.
-
Acute
o SOB
o Organ failure
o shock
Chronic
o pallor (pale skin, mucosal linings, nail beds, skin creases)
o fatigue
o + haemolysis: jaundice and gallstones
o + ineffective erythropoiesis: iron overload, heart and endocrine failure
o severe and congenital: growth retardation, bone deformities due to
reactive marrow hyperplasia
o related - signs of iron deficiency:
dizziness
hair loss
irritability
weakness
pica, pagophagia
1.2.
-
WBC
RBC
Hb
Haematocrit
Platelets
Iron tests
o
Serum iron
Ferritin => clear iron deficiency, but need to look at CRP as well,
as infection increases ferritin can mask iron deficiency
Condition
Serum Iron
Iron
deficiency
anaemia
Anaemia
of chronic
disease
Pregnancy
Low
Transferrin,
TIBC
High
(compensates)
Transferrin
saturation
Low
Ferritin
Hepcidin
Low
Low
Normal
High
High
Normal
High
Low
Protoporphyrin
High
LFTs
o
Aminotransferases
Alkaline phosphatase
Gamma-glutamyltranspeptidase
1.3.
1.3.1.
-
Causes of Anaemia
Think decreased production or increased destruction! (and more)
Decreased production
Bone marrow aplasia => aplastic anaemia
o
Drugs
Radiotherapy
Radiation
Autoimmune conditions
Folate/Vitamin 12 deficiency
Congenital
Cytotoxic drugs
Cancer
Leukaemias
Myeloproliferative disorders
1.3.2.
Myelofibrosis
Essential thrombocytosis
Increased destruction
Hypersplenism
Spherocytosis
Thalassaemia
Loss
Menstruation
Dilution:
o
Hypervolaemia
Pregnancy
1.4.
1.4.1.
-
1.4.2.
Causes of Microcytosis
Childhood:
o
Thalassamia
Adulthood:
o
Sideroplastic anaemia
Lead poisoning
Epidemiology
o
Aetiology
o
western world:
peptic ulcer
diverticular disease
gynaecological
developing world:
poor bioavailability
Pathogenesis
o
Investigations
o
FBC
Iron tests
LFTs
CRP
Blood film
Clinical features
o
May be asymptomatic
Hb low
MCV low
Erythropoietin high
Microscopic features
o
From podcast:
o
1.4.3.
-
Epidemiology
o
Aetiology
o
chronic infections
neoplasms
Pathogenesis
Microscopic Features
o
No other features
Clinical Features
o
1.4.4.
ferritin elevated
TIBC reduced
Diagnosis
o
Epidemiology
o Alpha is prevalent in the Far East
10
Aetiology
o Genetic
o different severities
minor/trait = heterozygous
major = homozygous
Pathogenesis
o One Hb chain is underproduced
o Other Hb chain precipitates => haemolysis via RBC membrane
damage
o Occurs while cells still in the bone marrow
Clinical Features
o If minor/trait then asymptomatic or minor anaemia, exacerbation
during pregnancy
o If major
osteopenia
o Iron accumulation
o ferritin increased
-
Treatment
o Promote healthy lifestyle and diet
o Folate supplements
o Iron chelators to prevent iron overload
o Lifelong transfusions if major trait
1.5.
11
Sideroplastic anaemia
BM produces sideroblasts instead of RBCs
Genetic or part of myelodysplastic syndrome
Inability to incorporate iron into Hb
Normocytic Anaemia
Causes
AOCD
cancer
1.6.
-
Macrocytic/Megaloblastic Anaemia
Epidemiology
o
F>M
Aetiology
o
o
-
Pathogenesis
o
12
Microscopic Features
o
Anisocytosis
Poikilocytosis
Nucleated RBCs
Bone marrow:
Hypercellular
Megaloblasts
Presentation
o
Symptoms of anaemia
Mild jaundice
1.6.1.
Liver disease
chemotherapy reagents
antifolate drugs
Severe hypothyroidism
Haemolytic anaemia/reticulocytosis
Liver disease
Myeloproliferative disease
Pregnancy
Haemolytic anaemia
a)
Aetiology
o
poor diet
elderly
pregnant women
drugs
Malabsorption
Celiac disease
Clinical Features
o
13
Measure serum and red cell folate and B12 levels to distinguish
Treatment
o
14
B12 absorbed via intrinsic factor which is produced in parietal cells by stomach,
then absorbed in terminal ileum
intrinsic factor aids absorption of B12 in small intestine (first B12 binds to
haptocorrin in the stomach, at higher pH to intrinsic factor)
Aetiology
o
After gastrectomy
poor diet
Clinical Features
o
Complications
o
Neuritis
Dementia
1.7.
-
15
Haemolytic Anaemias
1. Problems with Hb
Thalassaemia
Lead poisoning
Aetiology
Alloimmune reactions
o
Pathogenesis
loss
of
biconcave
SPHEROCYTOSIS
shape
=>
spherocyte
16
More HEREDITARY
4. Misc
Infections
Haemolytic
uraemic syndrome
HUS,
see histopath
chapter 6.10.
Miscoscopic Features
o
o
-
Clinical Features
17
Breakdown extravascular
Erythropoietin increased
Investigations
o
Include direct antiglobulin tests to check for antibodies and rule out
immune haemolytic anaemia
1.7.1.
Epidemiology
o Alpha is prevalent in the Far East
o Beta is prevalent in the Mediterranean
Aetiology
o Genetic
o different severities
minor/trait = heterozygous
major = homozygous
Pathogenesis
o One Hb chain is underproduced
o Other Hb chain precipitates => haemolysis via RBC membrane
damage
18
Clinical Features
o If minor/trait then asymptomatic or minor anaemia, exacerbation
during pregnancy
o If major
osteopenia
o Iron accumulation
o ferritin increased
-
Treatment
o Promote healthy lifestyle and diet
o Folate supplements
o Iron chelators to prevent iron overload
o Lifelong transfusions if major trait
1.7.2.
o
Epidemiology
Aetiology
B-chain abnormality = Hb-S
QuickTime and a
decompressor
are needed to see this picture.
causes of death
-
lung complications
stroke
infections
19
splenic sequestration
QuickTime and a
decompressor
are needed to see this picture.
20
Occurs in up to 7% in children
Exchange transfusion
Priapism (vaso-occlusive)
21
IV fluids
Hydration
IV antibiotics
transfusion
22
Prevention
Transfusion
sometimes difficult as optimal haematocrit for O2 carriage vs
increased viscosity, if too much transfused to raise Hb to normal
levels but if viscosity too high then further complications such as
stroke
alloimmunisation also a problem, sickle cell population has
different surface antigens than blood donors => sensitisation to
red cell antigens => cross matching becomes very difficult, e.g. U
antigens, patients become almost untransfusable, therefore limit
transfusion to severe cases such as chest crises, splenic
sequestration and stroke
Hydroxyurea
Oral chemotherapy reagent for myeloproliferative disorders or
CLL
Side-effect: increased production of fetal Hb which reduces
sickling, also neutrophil reduction, which can also be beneficial
23
24
This is from the podcast on PRV, for more notes, see Chapter 5. Leukaemia and
Myeloproliferative Disorders
symptoms
o vague
o reduced blood supply to various organs as result of increased blood
supply
o dizziness
o headaches
o visual disturbance
o tinnitus
o itch in extremities after hot bath
o stroke
o DVT
o Asymptomatic
Examination
o Facial plethora
o Splenomegaly in 60% of patients
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o Risk of thrombosis increases along with other risk factors such as being
male, obese or older
-
Relative polycythaemia
o Plasma volume decreases, RBCs themselves not increased
o Acute from dehydration, e.g. after diuretic intake or excessive alcohol
intake
o Chronic from kidney disease, obesity, hypertension, high alcohol and
tobacco intake
o May resolve when underlying cause is addressed
o Should be reported and investigate because it may be absolute
polycythaemia
Absolute polycythaemia
o Plasma volume normal
o 1* cause: disorder of haemopoietic stem cell
o 2* cause: when RBC cell mass increases due to increased erythropoietin
production
Excessive smoking
Renal cysts
Uterine fibroids
26
Mutations in EP receptor
Idiopathic polycythaemia
o Erythropoietin:
myeloproliferative disorder
acquired disease
o detection/distinction
Relative or absolute?
-
27
Bibliography
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