PBL 2 Flashcards
Non consanguineous
These are two individuals that are not related, they are further apart in terms of relation than second cousins.
Hepatosplenomegaly
disorder where both the liver and spleen swell beyond their normal size
Crackles
lung sounds that can be heard in
patients with pneumonia
Sonorous wheeze
low-pitched, course, loud,
low snoring or moaning sound, due to narrowing
of the large airways or an obstruction of the
bronchus
ESR - erythrocyte sediment rate
the rate at which RBCs sediment (settles
to the bottom of liquid) in a period of one hour;
elevated levels occur with inflammation,
anaemia, infection, etc.
Bilateral haziness
diffuse haziness that would
typically be called by inflammation, or thickening of tissues
Dactylitis
inflammation
of an entire digit, caused
by blocked blood
circulation
Hb electrophoresis
test to detect different types of haemoglobin
Nucleated RBCs
very immature forms of RBCs,
seen when there is a severe demand for RBCs to
be released by the bone marrow
Acute splenic sequestration crisis
refers to an
acute condition of intrasplenic pooling of large amounts of blood
Cefotaxime
antibiotic
Erythromycin
antibiotic
Peripheral blood smear
thin layer of blood
smeared on a glass microscope slide, and then stained in order to allow the blood cells to be examined via microscope
what is sickle cell anaemia
it is an autosomal recessive condition that affect the oxygen carrying capacity of haemoglobin molecules
what does autosomal recessive conditions mean that you need
Need two copies of the mutated gene n order to get sickle cel anaemia HbSS
what happens when you get one copy of the gene
- this means that you have a sickle cell trait which is HbAS
what is the mutation for sickle cell anaemia
- non conversed missense
- occurs in one of amino acid which encodes the beta globin chain on chromosome 11 at position 6
- converts glutamic acid to valine (thymine to adenine) in RNA A to U
what is haemoglobin A made out of
2 alpha, 2 beta chains
(dominates after 6
weeks of age)
what is haemoglobin S made out of
2 alpha, 2 mutant beta
chains
what is haemoglobin A2 made out of
2 alpha, 2 delta chains
what is haemoglobin F made out of
2 alpha, 2 gamma chains
(dominates up to 6
weeks of age)
what is haemoglobin F made out of
2 alpha, 2 gamma chains
(dominates up to 6
weeks of age)
Describe how to do a solubility test for the diagnosis of an SCA
- Is able to diagnose if there is HbS present
- It is a very cheap and paper based screening test
- It has 100% sensitivity to the presence of HbS
- It has 100% specificity to HbS
- You add 20μl blood to a solubility buffer (2.49 M
phosphate buffer) - You then add saponin and a reducing agent (sodium
hydrosulphite) - HbA and HbS are both identified in this test
How do you use blood smears for the diagnosis of sickle cell anaemia
Most peripheral smears will not show abnormal
haemoglobin
This is because HbS will only cause sickling in
hypoxaemia
In hypoxaemia, the HbS form long polymer fibres,
and the cells sickle
To induce hypoxaemia, 2% sodium metabisulphite
(antioxidant) is added to the blood sample
How do you treat sickle cell anaemia
Bone marrow transplant can potentially cure children
Hydroxyurea → drug which increases HbF production
→ this helps to reduce the symptoms and
complication of SCD
Antibiotics → reduce risk of infection
Pain relief → reduce pain levels
Blood transfusion → transfuse non-sickled blood into a
patient
Oxygen → increase O2 concentration in the blood
In the future? Possibly mutant ß-globin chain
switching → epigenetics
what is the selective advantage of sickle cell trait
Being a sickle cell carrier gives an individual a
protective advantage over non-carriers in malaria
This might be why sickle cell is still present in
malaria endemic regions
RBCs infected with malaria have lower O2 levels
This makes them sickle, and allows the RBCs to
degrade
As a result, the parasite dies
what is the mechanism for sickle cell trait protecting against malaria
P. Falciform infects an HbAS RBC
This requires higher oxygen consumption, and
decreases partial pressure of oxygen
This leads to sickling of RBCs and then subsequent
removal of the cells
Thus, the parasite is killed
What are the examples of other autosomal recessive disorders
- haemoglobin S - sickle cell anaemia
CFTR - resistance to tuberculosis - cystic fibrosis
HEXA - tay sachs
HBA1/HBA2 thalassemia
what is the difference between glutamic acid and valine
Glutamic acid
- charged
- polar
- tucks into haemoglobin
valine
- hydrophobic
- non polar
- sticks out of haemoglobin
describe sickle cell crisis
Describes several independent acute conditions
that occur in patients with SCD
Most of these crises last between 5-7 days
Infection, dehydration, and acidosis are all triggers
as they favour sickling
However, most of the time, there is no definitive
predisposing cause
what can cause a sickle cell crisis
Infection, dehydration, and acidosis are all triggers
as they favour sickling
how do you treat a vast-occlusive crisis
Treated with hydration, analgesics, and blood
transfusion
what is a Vasco-occlusive crisis caused by
Caused by sickled RBCs obstructing capillaries and
restricting blood flow to an organ
- Dactylitis → due to recurrent ischaemic necrosis of the
small bones in the hands and feet - Swelling persists for 1-2 weeks even after pain is
resolved - Infarction of abdominal and retroperitoneal organs
- Initially spleen enlarges
- Then undergoes auto-splenectomy
- Can lead to hepatic (liver) infarct
what is a splenic sequestration crisis
- this is an acute, painful enlargement of the spleen
what is a splenic sequestration crisis resulting in
Results in Hb levels falling, and a potential for
hypovolaemic shock
Because the spleen has narrow vessels, and is
responsible for clearing defective RBCs, the spleen is
commonly affected in SCD
What causes a splenic sequestration crisis
- caused by intrasplenic trapping of red blood cells
what is the damage of the splenic sequestration crisis
- Damage in spleen leads to an increased risk of infection
from encapsulated organisms (i.e. bacteria with a
protein coat) - Emergency → patient will die within 1-2 days without
treatment
what are the symptoms of acute chest syndrome
Classified by two of the following symptoms: - Chest pain - Fever - Pulmonary infiltrate/focal abnormality - Respiratory symptoms - Hypoxaemia - 80% of patients have a vaso-occlusive crisis during acute chest syndrome
what increases the risk of sickle cell disease
afro caribbean parents
what cases the…
- hepatosplenomegaly syndrome
- lung field rales/ sonorous wheeze
- low haemoglobin
- white cell count increase
- platelet count lowering
- high ESR
- chest radiograph with bilateral hazinesss
- diactylitis
- peripheral blood smear
Hepatosplenomegaly → splenic sequestration
syndrome
Lung field rales, sonorous wheeze → lung infection
Low haemoglobin → due to haemolytic anaemia
associated with SCD
White cell count increased → due to infection
Platelet count low → vaso-occlusive crisis → spleen
is blocked and so platelets can’t exit into the
circulation
High ESR → because RBCs are being destroyed
quicker and, therefore, need to be replaced quicker
Chest radiograph with bilateral haziness → lung
infection
Dactylitis → vaso-occlusive crisis in the vessels
leading to and from the peripheral digits
Peripheral blood smear → low oxygen levels lead to
sickling of sickle cell RBCs
what does genetic counselling teach
The genetic inheritance of SCD
Disease-related health problems e.g. splenic
sequestration syndrome
Future family planning
How do you cope with a child who has a chronic illness
- learn about the illness
- join a support group
- face the possibility of early death
- maintain open and honest communication
- share leadership
- include all family members in decision making
What is auscultation
this is the action of listening to a person’s lungs, heart and intestines during a physical examination in order to find a diagnosis
What is the difference between foetal and adult haemoglobin
Foetal Haemoglobin - has a higher affinity for oxygen than adults, can carry 30% more oxygen, this is because the maternal blood has to dissociate from oxygen in an area that has a low partial pressure for oxygen this means that the fatal haemoglobin needs to have an higher affinity in this area in order to bind to it - 2 alpha, 2 gamma chains (dominates up to 6 weeks of age)
Adult haemoglobin
- has 2 alpha chain and 2 beta subunits
- dominates after 6 weeks of age
- lower affinity for oxygen
What happens once the red blood cells are infected
parasitisation of AS red blood cells this increases the oxygen consumption and deceases the partial pressure of oxygen therefore the red blood cells sickle
- these red blood cells are removed as fewer surface proteins which adhere to the endothelium
What does hyroxycarbomide do
this is a form of treatment for sickle cell anaemia that promotes production of foetal haemoglobin so they can pick up more oxygen
- given to patients once a day
- drug is withdrawn and causes increase in haemoglobin
what are the ways of diagnosing sickle cell anaemia
- solubility test
- electrophoresis
- blood smear
who should receive genetic counselling
- parents of new borns with a sickle cell disorder or trait
- pregnant women/prenatal counselling
How do you do a electrophoresis of sickle cell anaemia
Able to differentiate between heterozygous (HbAS) and homozygous (HbSS) states
The charged glutamic acid AA changes the speed
which the sample moves
Therefore, in HbAS one strand moves much faster
than the other
On the other hand, in HbSS both strands move quickly
