Theme 2: Lecture 4 - Introduction to Anaemia Flashcards
Definition of anaemia
Hb concentration falls outside the normal range
What are the units of Hb
g/L
Clinical consequence of anaemia
Insufficient O2 delivery
Normal Hb range for children
110-160 g/L
Normal Hb range for women
115-165g/L
Normal Hb range for pregnant women
110-160 g/L
Normal Hb range for men
130-180 g/L
Haematocrit
- % RBC volume to entire blood volume
- 40-45%
RBC count
- Number of RBCs per litre
- 4x10^12/L
MCV
- mean cell volume
- 80-100fL
MCH
mean cell Hb
MCHC
mean cell Hb concentration
Anaemia symptoms
- Lethargy, fatigue
- Shortness of breath (At rest vs On exertion?)
- Palpitations
- Headache
- Worse symptoms if acute onset
Anaemia signs
- Skin pallor
- Pale conjunctivae
- Tachypnoea
- Tachycardia
Koilonychia
- Spoon shaped nails
- due to iron deficiency
Causes of anaemia
Problems of inadequate synthesis:
- Deficiency in necessary components
- Bone Marrow Dysfunction / Infiltration e.g., myelodysplasia or aplastic anaemia
Problems of blood loss or consumption:
- Bleeding
- Haemolytic
myelodysplasia
one of a group of cancers in which immature blood cells in the bone marrow do not mature, so do not become healthy blood cells
aplastic anaemia
body fails to produce RBCs in sufficient number
How can anaemias be classified
- Size of red cell
- Acute or chronic
- Underlying aetiology
What is the most common type of anaemia
Iron deficient
What causes iron deficiency
Bleeding:
- Occult gastro-intestinal blood loss: (GI Malignancy (never miss this) and GI peptic ulceration)
- Menstrual
- Renal tract
Inadequate intake:
- Dietary deficiency - Vegan/vegetarian diet
- Malabsorption - Coeliac and Crohn’s disease
Increased requirements:
-Pregnancy
Diagnostic tests for iron
- Serum ferritin (measure of iron stores)
- Serum Fe
- Serum transferrin
- Transferrin saturation %
What is serum ferritin
- Storage form of iron
- Low = iron deficient (high = iron overload or reactive)
serum iron
Labile in blood, so reflects recent intake of iron
What is serum transferrin
- Carrier molecule for iron from gut to stores
- Homeostatically goes up if iron is deficient
- Reflects total iron binding capacity (TIBC) of the blood
TIBC
- total iron binding capacity
- laboratory test that measures the blood’s capacity to bind iron with transferrin
% transferrin saturation
- Sensitive measure of iron status
- Reflects proportion of transferrin with iron bound
- Low TF saturation indicates iron deficiency
What are the iron studies like in iron deficient anaemia
- Serum iron: low
- Serum transferrin/TIBC: high
- % transferrin saturation: low
- serum ferritin: low
What are the iron studies like in anaemia of chronic disease
- Serum iron: low
- Serum transferrin/TIBC: low
- % transferrin saturation: normal
- serum ferritin: normal or high
What causes microcytic anaemia
- Iron deficiency
- Inherited disorders of haemoglobin (beta-thalassaemia trait)
What causes macrocytic anaemia
- B12 and folate deficiency
- Myelodysplasia (causes defective erythropoiesis)
What causes normocytic anaemia
- Anaemia of chronic disease
- Acute haemorrhage
- Renal failure (caused by low erythropoietin levels)
Anaemia of chronic disease
- disease caused by chronic inflammation and seen in conditions such as connective tissue disease, malignancy, and chronic infection such as TB
- functional deficiency of iron in the places that it’s required due to cytokines which impair the mobilization of iron from stores to cells where it’s needed in the bone marrow
haematinic deficiency
deficiency of any of the vitamins and minerals essential for normal erythropoiesis
what can RBCs look like in haematinic deficiency
microcytic/macrocytic
hypochromic
anisopoikilocytosis
Hypochromic
pale RBCs
anisopoikilocytosis
variation in size and shape of RBCs
haemoglobinopathy
inherited blood disorders in which the individual has an abnormal form of haemoglobin or decreased production of haemoglobin
What do RBCs look like in haemoglobinopathies
sickled
Haemolysis
rupturing of RBCs
Haemolytic anaemia
RBCs are destroyed faster than they are made
what do RBCs look like in haemolytic anaemia
polychromasia
polychromasia
large blueish RBCs
Pencil cells
long thin RBCs
Target cells
RBCs that look like a target with a bullseye in the middle
Reticulocyte count indicates
- Indicate rate of production of RBCs in the bone marrow
- Useful to monitor response to treatment
What is the reticulocyte count in precursor deficiencies
low
What is the reticulocyte count if the bone marrow has been infiltrated
low
What is the reticulocyte count in chronic bleeding
high
What is the reticulocyte in haemolysis
high
dyspepsia
indigestion
melena
black tarry faeces discoloured by presence of digested blood, usually reflects significant bleeding in upper GI tract
menorrhagia
abnormally heavy bleeding on menstruation
Celiac disease
autoimmune disease that occurs in genetically predisposed people where the ingestion of gluten leads to damage in the small intestine.
Crohn’s disease
A type of inflammatory bowel disease
What things do you need to ask about history when anaemia is suspected
- GI Symptoms: Dyspepsia / Reflux, Change in bowel habit (?melaena), Weight loss?
- Menstrual History ?menorrhagia
- Bowel history ?coeliac / Crohn’s disease
- Dietary history
- Travel History
- Ethnic Origin
- Family History
What is megaloblastic anaemia caused by
vitamin B12 or folate deficient anaemia
What are the RBC appearance in megaloblastic anaemia
- Macrocytic
- MCV > 100
Appearance of WBCs in megaloblastic anaemia
hyper segmented neutrophils (more than 4 nuclear lobes)
what is pernicious anaemia a result of a deficiency in
Vitamin B12
Why is there B12 deficiency in pernicious anaemia
- Gastric parietal cells are destroyed by autoimmune causes
- Leads to a deficiency in intrinsic factor (as it’s secreted by parietal cells)
- Intrinsic factor is required to bind to B12 to facilitate its absorption
- Body can’t absorb B12 in the terminal ileum where intrinsic factor is located
How is pernicious anaemia treated
with B12 injections (as it can’t be absorbed in the gut)
-load initially with 5 doses on alternate days and then once every 3 months
What causes vitamin B12 deficiency
Dietary:
- Strict vegans (B12 found in diary produce)
- Supplement with oral B12
Malabsorption:
- Coeliac disease and Crohn’s disease
- Post gastric / ileal surgery
Which drugs cause folate deficiency
- Phenytoin
- Methotrexate
What causes folate deficiency
- Dietary – common
- Malabsorption: Coeliac, Crohn’s disease
- Excess Utilisation: Chronic haemolysis, Pregnancy
- Alcohol
- Drugs
What causes anaemia of chronic disease
- Chronic inflammation
- Chronic infection e.g. TB
- Auto-immune conditions e.g. rheumatoid arthritis
- Cancer
- Renal failure
Characteristics of anaemia of chronic disease
- Poor utilisation of iron in the body
- Dysregulation of iron homeostasis
- Impaired proliferation of erythroid progenitors
What does poor utilization of iron in the body mean
- Iron is stuck in macrophages of the reticuloendothelial system
- There is poor mobilisation of the iron from the stores into the erythroblasts
What happens in dysregulation of iron homeostasis
- Decreased transferrin
- Increased ferritin (acute phase reactant)
- Increased hepcidin
Hepcidin
protein that is a regulator of iron metabolism
acute phase reactants
inflammation markers (proteins) that exhibit significant changes in serum concentration during inflammation
What causes impaired proliferation of erythroid progenitors
- blunted response to EPO
- iron is functionally unavailable
What causes sickle cell anaemia
point mutation in the beta globin gene causing HbS
Describe the blood cells in sickle cell anaemia
- Increased turnover of red cells = survival approx 20 days due to haemolysis
- Raised reticulocytes >10%
How is sickle cell anaemia managed
- analgesia
- hydration
- transfusion
Describe a sickle cell crisis
-Triggered by low blood O2 level
-Vaso-occlusive due to sickling in the vessels
Causes ischaemia leading to pain, necrosis and -potential organ damage
Sickle cell trait
- heterozygous,
- 50% HbS and 50% HbA
- much lower risk of sickling and crisis
- resistance to malaria infection
Describe HbS
- forms long filamentous strands
- insoluble at low O2 tension
- RBCs become inflexible + spiky leading to crisis
Clinical features of thalassaemia
- enlarged spleen, liver, and heart
- bones may be misshapen (frontal bossing)
frontal bossing
prominent, protruding forehead
What is thalassaemia
- Insufficient production of normal Hb, imbalance of alpha and beta chains
- Inherited autosomal recessive, either alpha or beta thalassaemia
Full blood count characteristics of beta thalassaemia
- Microcytic
- Hypochromic
What is beta thalassaemia diagnosed by
- Hb electrophoresis
- Blood film
Electrophoresis
A laboratory technique used to separate DNA and RNA or protein molecules based on their size and electrical charge
Beta thalassaemia major
- homozygous
- disease
- requires life-long transfusions
Beta thalassaemia minor
- heterozygous
- carrier
- aka Beta-thal trait
- clinically healthy
How is bone marrow infiltration investigated
Bone marrow sample obtained from iliac crest:
- aspirate film for morphology of cells
- trephine biopsy for histological section
trephine
a hole saw used in surgery to remove a circle of tissue or bone
Management of chronic anaemia
Treat the underlying cause:
Iron supplementation (oral ferrous sulphate 3 months)
Folic acid (oral folate for 3 months)
B12 (load initially then injections every 3 months)
Erythropoietin (EPO) weekly sub-cut injections in patients receiving haemodialysis or with kidney failure
What does long term transfusion cause
- Iron overload (iron deposition in organs)
- Allo-antibodies (to foreign red cells)
- Therefore have to be careful
