S5 L1 - Haemoglobinopathies and Haemolytic Anaemias Flashcards
- *Haemoglobinapthies**
- What are these disorders?
- What is the normal structure of haemoglobin
- 2 major well known haemoglobinapthy disorders and briefly explain them
- *Haemoglobin:**
- 3 main types of haemoglobin
- Why do these change?
- Which is the main form just before birth? What happens after birth?
Haemoglobinapthies
- What are these disorders?
Disorders with defects in globin chain synthesis, inherited autosomal recessive
- What is the normal structure of haemoglobin
Haemoglobin is a tetramer of 4 globin polypeptide chains; 2 alpha (α) and two non-alpha chains (β, δ or γ). Each globin chain is complexed with an oxygen binding haem group.
- 2 major well known haemoglobinapthy disorders and briefly explain them
Sickle cell anaemia: Globin gene mutations alter structure/function/stability of the haemoglobin tetramer
Thalassaemias: Globin gene mutation reduce expression of specific protein resulting in imblanace in the composition of the haemoglobin tetramer
Haemoglobin:
- 3 main types of haemoglobin
HbA: 2 alpha/2 beta chains
HbA2: 2 alpha/2 delta chains
HbF: 2 alpha/2 gamma chains
- Why do these change?
Different Haemoglobins expressed during development as an adaptive response to variations in oxygen requirements
- Which is the main form just before birth? What happens after birth?
• Fetal haemoglobin (HbF) main form just before birth.
• HbA commences before birth and steadily increases to become dominant after birth
- *Thalassaemia**
- What is the normal expression of globin genes?
- What happens in thalassaemia?
- Which ethinicity’s is each type of thalassaemia most common in?
- *Alpha-thalassaemia:**
- How many alpha-globin genes do humans have?
- How many ‘types’ of this type of thalassaemia are there?
- Describe each type and the symptoms
Thalassaemia
- What is the normal expression of globin genes?
Normal expression of globin genes is under tight control to ensure a 1:1 ratio of α to non–α globin chain proteins
- What happens in thalassaemia?
Defects in this regulation of expression of globin genes can result in abnormalities in both the relative and absolute amounts of the globin chain proteins and can result in:
— β thalassaemia (β globin gene expression affected)
— α thalassaemia (α globin gene expression affected)
- Which ethinicity’s is each type of thalassaemia most common in?
Traditionally more prevalent in South Asian, Mediterranean, Middle east (β thalassaemia) and Far East (α thalassaemia) populations
Alpha-thalassaemia: DELETION OF ALPHA CHAINS
pic
- *Beta-Thalassaemia:**
- Which globin chain
- Which chromosome
- What does the mutation lead to…
- How many types of beta-thalassaemia are there? Name and explain all types
Beta-Thalassaemia TOTAL ABSENCE OF PRODUCTION (NOT DELETION)
(pic)
- *Thalassaemia:**
- Blood film (what does this show)
- What happens to excess unaffected globin chains? How does this cause even more problems? Which other type of anaemia do patients with thalassamia therefore also suffer from?
- *Consequences of Thalassaemia**
- 3 main and try and link these together
• Extramedullary haemopoiesis occurs in an attempt to compensate but results in splenomegaly, hepatomegaly and expansion of haemopoiesis into the bone cortex ..this impairs growth and causes classical skeletal abnormalities
• Reduced oxygen delivery leads to stimulation of EPO which further contributes to the drive to make more defective red cells
• Iron overload is major cause of premature death and occurs due to:
— Excessive absorption of dietary iron due to ineffective haematopoiesis
— Repeated blood transfusions required to treat the anaemia
• Reduced Life expectancy
- *Thalassaemia - Treatments**
- remember acronym as well…
(pic)
FITI SHC
- *Sickle Cell Disease**
- Inheritance pattern
- What is Codon change mutation, which aa is changed?
- How is a heterozogous mutation written as?
- How is a homozygous mutation written as?
- Inheritance pattern
Autosomal recessive disease resulting from mutation of β-globin gene
- What is Codon change mutation, which aa is changed?
GAG codon changed to GTG resulting in glutamic acid being substituted by valine at position 6.
- How is a heterozogous mutation written as?
Mutant haemoglobin molecule containing this mutated β-globin protein referred to as Haemoglobin S (HbS). Heterozygous HbS carrier state causes a mild asymptomatic anaemia
- How is a homozygous mutation written as?
HbSS = homozygous sickle cell anaemia, is most common cause of severe sickling syndrome
- *Sickle cell disease:**
- What is this disease
- What happens in this disease
- 3 types of crises
- Consequences of the crisis (list)
Treatments
What is this disease/what happens:
• Anaemia usually mild and well tolerated as HbS readily gives up oxygen in comparison to HbA
• Problems come in low oxygen state as deoxygenated HbS forms polymers that cause red cells form a sickle shape
• Irreversibly sickled red are cells less deformable and can cause occlusion in small blood vessels – ‘sticky’
What happens in this disease
3 types of crisis
Consequences of the crisis
all - see pic
Treatments:
Folic acid
Penicillin and vaccinations as hyposplenic
Red cell exchange
Hydoxycarbamide - increase HbF levels and other effects
- *Haemolytic anaemia**
- Normal lifespan of RBC
- Where does haemolysis occur in the body?
- What tries to compensate for HA?
- When does anaemia develop due to HA?
- Causes of HA
- Lab findings
- Some signs of haemolytic anaemia
- Why does splenomegaly occur?
- What is the risk of a massive sudden haemolysis (and a cause of sudden haemolysis)
- Normal lifespan of RBC
- Where does haemolysis occur in the body?
- What tries to compensate for HA?
- When does anaemia develop due to HA?
- Causes of HA
- Lab findings
see pic for all
- Some signs of haemolytic anaemia:
Jaundice due to bilirubin build up, pigment gallstones…
- Why does splenomegaly occur?
overworking of red pulp (splenomegaly then leads to further anaemia)
- What is the risk of a massive sudden haemolysis (and a cause of sudden haemolysis)
Massive sudden haemolysis e.g. from incompatible blood transfusion can cause cardiac arrest due to lack of oxygen delivery to tissues & hyperkalaemia due to release of intracellular contents
- *Inherited defects in red cell membrane structure**
- *-** Name two key conditions
- What does the mutation affect
- What does this result in…
Inherited defects in red cell membrane structure
- Name two key conditions and mutation:
Hereditary spherocytosis:
Ankyrin defective
Hereditary eliptocytosis: HES
Spectrin defective
Results in:
Both are not as flexible, easily damaged, removed by the spleen (lead to haemolytic anaemia)
- *Acquired damage**
- List of types of damage
- One of the damage types is mechanical damage, name of this type of anaemia and describe 2 ways mechanical damage can occur
- Blood film - of haemolytic anaemia caused by mechanical damage
- List of types of damage:
• Mechanical damage
• Heat damage from severe burns
• Osmotic damage (drowning in freshwater)
- One of the damage types is mechanical damage, name of this type of anaemia and describe 2 ways mechanical damage can occur
Microangiopathic haemolytic anaemias result from mechanical damage e.g.
• Shear stress as cells pass through a defective heart valve (e.g. in aortic valve stenosis).
• Cells snagging on fibrin strands in small vessels where increased activation of clotting cascade has occurred (e.g. in Disseminated Intravascular coagulation)
-
Blood film - of haemolytic anaemia caused by mechanical damage:
Schistocytes Fragments resulting from mechanical damage are called. The presence of schistocytes is a good indicator that some form of pathology is present
- *Autoimmune Haemolytic anaemia
- ** What is this, what happens, how does it lead to haemolytic anaemia
