Anaemia Flashcards
What are the general causes of anaemia?
Not enough red blood cells
Not enough haemaglobin within red blood cells
What are the causes of anaemia to do with erythropoiesis in the bone marrow?
Reduced erythropoiesis
Dyserythropoiesis
Haemaglobin synthesis
What are the causes of reduced erythropoiesis?
Chronic kidney disease
Empty bone marrow
Infiltration of bone marrow
Why does chronic kidney disease lead to reduced erythropoiesis?
Kidneys don’t produce erythropoietin
Why does empty bone marrow lead to reduced erythropoiesis?
Lack of cells in bone marrow
lack of precursors of red blood cells
What can cause bone marrow to be empty?
Chemotherapy
Parvovirus infection
Aplastic anaemia
Why does infiltration of bone marrow lead to reduced erythropoiesis?
Lack of normal haematopoietic cells
lack of precursors of red blood cells
What can bone marrow be infiltrated with?
Cancer cells
Fibrous tissue
What is the term for bone marrow infiltrated by fibrous tissue?
Myelofibrosis
How is reduced erythropoiesis by chronic kidney disease treated?
Give patient erythropoietin hormone
What are the causes of dyserythropoiesis?
Anaemia of chronic disease
Myelodysplastic syndromes
Which chronic conditions might anaemia be a symptom of?
Chronic inflammatory conditions
- inflammatory bowel disease e.g. crohn’s, ulcerative colitis
- rheumatoid arthritis
Chronic infection
-TB
How do some chronic conditions cause anaemia?
Bone marrow doesn’t respond to erythropoietin
Increased activity of macrophages
-circulating red cells have reduced lifespan
Inflammatory cytokines increase production of hepcidin
- less iron absorption in gut
- less iron release from macrophages
How does anaemia of chronic disease appear on a blood film?
Anaemia can be
- microcytic
- normocytic
- macrocytic
What are the levels of inflammatory markers in anaemia of chronic disease? Give examples
E.g. ferritin
CRP
both raised
How is anaemia of chronic disease treated?
Treat the underlying cause of the anaemia
What is the pathophysiology of myelodysplastic syndromes?
Mutations in cells of bone marrow
As a result
- do not mature
- produce clones of themselves
How do myelodysplastic syndromes cause anaemia?
Proper red blood cells not produced
Red blood cells prematurely destroyed by reticuloendothelial system
How does anaemia caused by myelodysplastic syndromes appear on a blood film?
Macrocytic - red blood cells are large
How is myelodysplastic syndrome diagnosed?
Look at chromosomal changes in bone marrow cells
Look at bone marrow cells and blood film under microscope
How is anaemia caused by myelodysplastic syndromes treated?
Chronic transfusions of red blood cells
Chemotherapy followed by stem cell transplantation in younger patients
What can myelodysplastic syndromes develop into?
Acute leukaemia
What are the causes of anaemia to do with haemaglobin synthesis in the bone marrow?
Lack of iron
Lack of vitamin B12, folate
Genetic disorders
What are vitamin B12 and folate required for?
Nuclear maturation
nuclear division
Cell division
What is seen on a blood film with vitamin B12 and folate deficiency?
Macrocytic - red blood cells are large
What causes macrocytic anaemia with vitamin B12 and folate deficiency?
Cytoplasm develops faster than nuclear maturation, nuclear division and cell division
red blood cell precursors have large nuclei, are large themselves
What do neutrophils look like with vitamin B12 and folate deficiency?
Hypersegmented nuclei
What can prolonged vitamin B12 and folate deficiency lead to?
Pancytopenia - low neutrophils and platelets as well as low red blood cells
What is the term for anaemia caused by vitamin B12 and folate deficiency?
Megaloblastic anaemia
What are the genetic disorders of haemaglobin synthesis?
Sickle cell
Thalassaemia
What is the inhertiance pattern of sickle cell anaemia?
Autosomal recessive
What is the genotype of sickle cell anaemia?
HbS HbS
What is the cause of sickle cell anaemia?
Point mutation in B-globin gene
Valine replaced by glutamate
What are the symptoms of sickle cell anaemia?
Anaemia
Haemolytic crises
Vaso-occlusive crises
Aplastic crises
How severe is the anaemia in sickle cell anaemia? Why?
Mild
because HbS gives up oxygen more readily than HbA
What happens to HbS with oxygen gas exchange?
Deoxygenated HbS
forms polymers of HbS
How do the polymers of HbS affect red blood cells?
Cause red blood cells to sickle - form crescent shape
Damage red blood cell membrane
How do vaso-occlusive crises present?
Pain in ischaemic area
Which tissues and organs are usually involved in vaso-occlusive crises? How?
Brain - infarct
Lung - infarct
Spleen - infarct, atrophy
Kidney - infarct
Femur - avascular necrosis of head
Skin - ulcers
What can trigger a sickle cell crisis?
Temperature change e.g. cold
Stress e.g. infection
How do sickled red blood cells affect blood flow?
Form thromboses in small blood vessels
block blood flow
give ischaemia
HbS is common in which ethnic group? Why?
African people
because it confers protection against malaria
What are the two types of thalassaemias?
Alpha
Beta
What are the types of alpha thalassaemia?
Carrier state
A-thalassaemia trait
HbH disease
Hydrops fetalis
What is the genetic defect in the carrier state of alpha thalassaemia?
Deletion of a single a-globin gene
What are the symptoms of the carrier state of alpha thalassaemia?
Asymptomatic
What is the genetic defect in the a-thalassaemia trait?
Deletion of two a-globin genes
maybe two on same chromosome, or one on each chromosome
What are the symptoms of a-thalassaemia trait?
Mild anaemia
What is the genetic defect of HbH disease?
Deletion of three a-globin genes
What is produced in HbH disease?
Tetramers of b-globin chains
called HbH
What are the symptoms of HbH disease?
Severe anaemia
What appears on a blood film with HbH disease?
Target cells
Heinz bodies
What is the genetic defect in hydrops fetalis?
Deletion of all four a-globin genes
What is produced in hydrops fetalis?
In the foetus
Gamma-globin tetramers produced
Called HbBart
Does a foetus with hydrops fetalis usually survive? Why?
No
intrauterine death
HbBart is unable to deliver oxygen to tissues
What are the types of B-thalassaemia?
B-thalassaemia trait
B-thalassaemia major
What is the genetic defect in B-thalassaemia trait?
Deletion of one b-globin genes
What are the symptoms of B-thalassaemia trait?
Mild anaemia
What is the genetic defect in B-thalassaemia major?
Deletion of both b-globin genes
What are the symptoms of B-thalassaemia major?
Severe anaemia
When do the symptoms of B-thalassaemia major manifest? Why?
6-9 months after birth
when HbF switches to HbA
b-globin chains only produced for HbA
How is B-thalassaemia major treated?
Transfusions
What does a blood film with thalassaemia look like? Why?
Hypochromic
due to lack of Hb
Microcytic
How are red blood cells affected by thalassaemia?
Other globin chain produced in excess
precipitates in red blood cell
Developing red blood cells destroyed within bone marrow
Mature red blood cells destroyed within spleen
How are organs affected by thalassaemia? Why?
Extramedullary haemopoiesis in liver and spleen
giving hepatomegaly, splenomegaly
Expansion of haemopoiesis into bone cortex
gives skeletal abnormalities
Stimulation of erythropoietin production in kidneys
How is iron affected by thalassaemia?
Iron overload
- excess absorption of iron in diet, stimulated by ineffective erythropoiesis
- repeated blood transfusions
How is thalassaemia treated?
Transfusions with iron chelation
Folate
What do target cells look like and why?
Darker region in centre of red blood cell
because Hb has precipitated there
What are the causes of anaemia to do with red blood cells?
Defects in red blood cell
- structure
- metabolism
Loss of red blood cells
What is the most common inherited condition to do with a defective red blood cell membrane leading to anaemia?
Hereditary spherocytosis
What are spherocytes?
Abnormal red blood cells
are spherical in shape
What are elliptocytes?
Abnormal red blood cells
rod-like shape
What are acanthocytes?
Abnormal red blood cells
irregular shape
What are the causes of acquired defective red blood cell membranes?
Mechanical damage
Heat damage - burns
What are some causes of mechanical damage to red blood cells?
Heart valves
Vasculitis
Microangiopathy
DIC
What is a shistocyte?
Fragment of red blood cell
What are some defects in metabolism that lead to anaemia?
G6PDH deficiency
Pyruvate kinase deficiency
What are some causes of loss of red blood cells?
Acute - haemorrage
Chronic - ulceration, cancer, excessive menstruation
How might chronic blood loss present? Why?
Hypochromic microcytic anaemia
due to development of iron deficiency
What are the causes of anaemia to do with the reticuloendothelial system?
Haemolytic anaemia
What is haemolytic anaemia?
Anaemia caused by increased red blood cell destruction
Where does the extra red blood cell destruction occur in haemolytic anaemia?
Intravascular - within blood vessels
Extravascular - reticulendothelial system in spleen, bone marrow, liver
What are the causes of haemolytic anaemia?
Defective red blood cells
as with many of the causes of anaemia
Autoimmune haemolytic anaemia
What is the pathophysiology of autoimmune haemolytic anaemia?
Autoantibodies against bind to red blood cell membrane proteins
spleen destroys those red blood cells
What are the types of autoimmune haemolytic anaemia?
Warm, IgG
Cold, IgM
What are the key lab features of autoimmune haemolytic anaemia?
Increased reticulocytes
Increased bilirubin
Increased LDH
Why are reticulocytes increased with autoimmune haemolytic anaemia?
Bone marrow is producing more red blood cell
to compensate for the increased destruction
Why is bilirubin increased with autoimmune haemolytic anaemia?
Increased breakdown of red blood cells, haemaglobin, haem
haem is broken down into bilirubin
Why is LDH increased with autoimmune haemolytic anaemia?
Red blood cells are rich in this enzyme
How is a shistocyte produced?
Mechanical damage to red blood cells
What is seen in a blood film with myelofibrosis? Why?
Red blood cells are tear-drop shaped
because were squeezed through fibrotic tissue in bone marrow