SCD Both Adults And Kids And Kidney Diseases Flashcards
Define SCd and hemoglobinopathies
How is HbS formed?
Normal human haemoglobin have how many types and state them
Which type predominates in the first year of life
is one of the disorders in a broad group of hemoglobinopathies.
- Hemoglobinopathies - inherited/genetic disorders that results into abnormal production of one of the globin chains that forms the hemoglobin.
- In SCD, the beta chain is affected by a mutation that results into a formation of an abnormal hb called HbS
NB;- HbS formed by a point mutation, in which glutamic acid is substituted with valine at position 6 in the beta hb chain gene.
Normally human have the following types of hb;- ✓HbA- 2alpha +2beta chains
✓HbA2- 2alpha + 2 delta chains
✓HbF- 2alpha + 2gamma chains
HbF
HbA predominates (96%), with HbA2 making about 2-3% -Simply presence of HbS makes the disorder so called Sickle Cell Disease. True or false
What are the types of SCD and explain
What is the second most common type of SCd
- Sickle Cell Anemia- homozygous form, in which both hemoglobin are HbS ie. (HbS,HbS) - Severest form.
- Sickle Cell Trait- heterozygous with half of hb being normal and half being sickle hb ie.(HbS,HbA). -No symptoms unless under low oxygen tension
- Sickle cell beta thalathemias- heterozygous form but with the concentration normal hb being higher than sickle hb. Mild form
4.Hemoglobin S-C disease- there is no normal hemoglobin.
-It’s form is HbS,HbC.
-Similar presentation to Sickle Cell Anemia except
mild and less frequent.
-Similar mutation forms HbC except Glutamic acid is substituted by lysine.
Hemoglobin S-C disease
Where does sickle cell gene originate from
And make have equal chance of getting it as females do true or false
Sickle gene originates from Africa and India but because of globalisation its now spreading world wide (1 per 625 live births in America, Medscape).
-Thus highest incidence are found in Subsaharan Africa, India and Middle East. Common in Africa, Mediterrenian and Middle East
-M:F=1:
True
-Median age to acquire renal failure is 23.1 years and life expectancy is 27 years regardless of dialysis (medscape) ie. SCA
True or false
What is the pathogenesis of SCD
True
- SCD is caused by a point mutation at position 6 of the beta hb gene in which a hydrophilic glutamic acid is replaced by valine.
- The susceptible RBCz once subjected to an oxygen tension of <40mmHg for about 2-4 minutes they become deoxygenated.
- Deoxygenated hb undergoes hydrophobic interaction with adjacent sickle hb forming large polymer and thus RBC becomes less deformable and acquire sickle shape.
- Rigid RBCs obstruct microvasculature causing tissue hypoxia which precipitates further sickling.
- Sickle cells rapidly hemolyze and have a life span of about 10- 20 days
The initiation of polymerization may be incomplete and reversible if re-oxygenation occurs early in the process. Repetitive exposure to alternating deoxygenated and oxygenated states can lead to membrane distortion, oxidative damage and irreversible sickling.
What are the clinical features of SCA
State the types of sickle cell crisis
What ar ethe factors that can precipitate sickle cell crisis
Clinical features of SCA:-
- Chief cause for admission of patients is Sickle cell crises.
- This includes the following;✓ Vaso-occlusive crisis.
- Pain Crisis
- Splenic sequestration - Acute Chest Syndrome ✓Aplastic Crisis.
✓Hemolytic Crisis
SC crises:• Infections • Low oxygen tension • Concomitant medical conditions (e.g., sarcoidosis, diabetes mellitus, herpes) • Dehydration • Acidosis • Extreme physical exercise • Physical or psychologic stress • Alcohol •
•
•
• Pregnancy
• Cold weather
Explain VOC(vasooclusive crisis)
-due to obstruction of microvasculature by rigid sickle cells.
Painful crises- can affect any part but is chiefly expirienced in the abdomen, bones, joints and soft tissues
-Starts suddenly, very severe, and it may last for several hours.
-Commonly long bones are affected, but in the 1st 18 months can involve metatarsals and metacarpals causing dactylitis (painfull swelling hands and feet)
What is splenic sequestration
Splenic sequestration-
- When vasooclusion occurs in the spleen, the micro vessels blocked and blood accumulates in the spleen.
- Causes rapid enlargement and it’s a life threatening medical condition.
- Common in the first five years of life and may cause splenic infarction (autosplenism) at the end of childhood.
- Sequestration causes worsening of baseline anemia and increase risk of infection by encapsulated organism
- This includes H.influenza, S.pneumoniae, S.typhi and N.meningitidis.
Explain acute chest syndrome
Acute chest syndrome;-
- Commonly characterized by chest pain, fever, cough, tachypnea, pulmonary infiltrates, hypoxemia.
- Medical emergency is commonly precipitated by chest infections in children.
Explain hemolytic crisis and aplastic crisis
APLASTIC CRISIS
- Worsening of baseline anemia due to infection of
parvovirus B-19.
- This is single stranded RNA virus that is acquired by respiratory droplets and a special philia for erythrocytes progenitor
- Thus switches off RBC production and causes drastic drop of reticulocyte counts.
3. HEMOLYTIC CRISIS - accelerated breakdown of RBC that occurs with coexistence of G6PD deficiency.
- G6PD is a recessive X linked disorder that results to deficiency of the enzyme reqiured for formation glutathione in PP pathway
-Glutathione is required for clearing free radicals to prevent oxidative damage
Name other clinical manifestations of SCD
Other clinical manifestations;-
CNS –major devastating manifestation is stroke that is normally ischemic but can be hemorrhagic in adults after rupture of aneurysm.
-convulsions occurs concurrently with stroke but can occur isolated or with acute chest syndrome.
EYE- Para orbital infarction may lead to ptosis and also retinal vascular manifestation.
PRIAPISM- Sustained, painful and unwanted penile erection in SCD. Recurrent episodes may lead to fibrosis and impotence.
LEG ULCERS- Due to minor injuries especially on the malleoli. And because poor circulation healing is delayed and infections are established.
CHOLELITHIASIS- This is due to rapid hemolysis of RBC causing hyperalbuminaemia that causes formation of bile stones.
RENAL MANIFESTATIONS- Vasooclusion of renal small vessels causes ischemic injury and hence renal failure insues.
VIRAL HEPATITIS- Due to multiple blood transfusion
How is SCd diagnosed
Investigated
Attacks are diagnosed clinically, i.e. there is no gold standard diagnostic test. Hemolysis (anemia and jaundice) is often present, although for painful crises the
diagnosis depends essentially on how the patient describes the pain. LAB INVESTIGATION
For Screening, Diagnosis and Confirmation
• Sickling test (Hemoglobin S solubility test and sodium metabisulfite test), not for infants. Useful after 6month from birth.
• Newborn Screening: HPLC fractionation (High performance liquid Chromatography) and thin Layer/Isoeletric focusing.
• Abnormal hemoglobin forms are detected on hemoglobin electrophoresis, a form of gel electrophoresis on which the various types of hemoglobin move at varying speed. Sickle cell hemoglobin (HbSS) and Hemoglobin C with sickling (HbSC)—the two most common forms—can be identified from there.
• DNA analysis. This test is used to investigate alterations and mutations in the genes that produce hemoglobin components. It may be performed to determine whether someone has one or two copies of the Hb S mutation or has two different mutations in hemoglobin genes (e.g., Hb S and Hb C). Genetic testing is most often used for prenatal testing: amniotic fluid may be tested at 14 to 16 weeks to provide a definitive answer.
Other tests that may be used to help evaluate someone who is suspected of having or who is known to have sickle cell trait or disease include:
- Complete blood Count (CBC)
- Blood Smear
- Iron Studies
- LFT
- RFT
- Electrolytes
- Chest X-ray in Acute Chest Syndrome
- TransCranial Doppler Ultrasound (TCD),MRI (with or without angiography) and Neuropsychometric studies (NPM)
How is SCD treated
How is VOC treated
Febrile illness
TREATMENT
• Children with fever are screened for bacteremia i.e. complete blood count, reticulocyte count and blood culture taken. Younger children (varies from center to center) are admitted for intravenous antibiotics while older children with reassuring white cell counts are managed at home with oral antibiotics. Children with previous bacteremic episodes should be admitted.
Painful (vaso-occlusive) crises
• Most patients with sickle cell disease have intensely painful episodes called vasoocclusive crises. The frequency, severity, and duration of these crises vary tremendously, however. Painful crises are treated symptomatically with analgesics; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) “not applicable in our setting” devices are commonly used in this setting. Diphenhydramine is effective for the itching associated with the opioid use.
• NB: analgesia, Oxygen, hydration and warmth.
How is acute chest crisis treated
Acute chest crises
• Management is similar to vaso-occlusive crises with the addition of antibiotics (usually a quinolone or macrolide, since wall-deficient [“atypical”] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation. Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple blood transfusion or exchange transfusion is indicated. The latter involves the exchange of a significant portion of the patients red cell mass for normal red cells, which decreases the percent hemoglobin S in the patient’s blood.
Hydroxyurea
• The first approved drug for the causative treatment of sickle cell anemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al) and shown to increase survival time in a study in 2003. This is achieved by reactivating fetal hemoglobin production in place of the hemoglobin S that causes sickle cell anemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but it is likely that the benefits outweigh the risk
How is splenic sequestration crisis treated
SPLENIC SEQUESTRATION CRISIS,
• Treatment includes early intervention and maintenance of hemodynamic stability using isotonic fluid or blood transfusions.
• Careful blood transfusions with red blood cells are recommended to treat both the sequestration and the resultant anemia.
• Blood transfusion aborts the red blood cell sickling in the spleen and allows release of the patient’s blood cells that have become sequestered, often raising the hemoglobin above baseline values.
• Typically recommend only 5 mL/kg of red blood cells because the goal is to prevent hypovolemia.
- Blood transfusion that results in hemoglobin levels above 10 g/dL may put the patient at risk for hyperviscosity syndrome because of the risk that that patient may release the blood within the spleen.
- If there is recurrent episode Prophylactic splenectomy is the only choice for preventing future life threating episode.
How is priapism treated
PRIAPISM
• The optimal treatment for acute priapism is unknown. Acutely, supportive therapy, such as a hot shower, short aerobic exercise, or pain medication, is commonly used by patients at home.
• A prolonged episode lasting >4 hr should be treated by aspiration of blood from the corpora cavernosa
• Urology consultation is required to initiate this procedure, with appropriate input from a hematologist.
