Lung In Sickle Cell Disease Flashcards
HbS gene is protective against:
Malaria
Most severe form of SCD
Sickle cell anemia (HbSS)
Amino acid substitution in HbSS
Valine for glutamic acid
Structural changes in HbS
When deoxygenated, beta subunit of HbS is exposed and polymerizes with other Hgb tetramers, causing aggregates (crystals) that distort RBC membrane. After exposure to hypoxic or acidic environment, there is loss or K and increases in free Ca, causing dehydration. These cause membrane to stiffen and the RBC to be sickle shaped, subject to hemolysis and causing obstruction in small blood vessels.
Pathogenesis of SCD
-Sickle cell is deficient in antioxidant and produces oxidant species.
-Hemolysis produces free Hb and extra cellular heme, which is proinflammatory and a damage-associated molecular pattern molecule (DAMP).
-Release of neutrophil extracellular traps (NET)
-Inhibition of NO causes increased cellular adhesion and diminished vasodilation
-Enhanced adhesion of sickle cells to each other, endothelium, and neutrophil causes VASO-OCCLUSIVE CRISIS (VOC)
SCD in newborns
Asymptomatic due to HbF
Manifestations at 10-12 weeks
Age group with highest incidence of ACS
2-4 years old
Most important risk factor for development of SCLD
Recurrent ACS
ACS is more common and more severe in this subtype
HbSS
Incidence of ACS is inversely proportional to __ and directly proportional to __
Inverse:
HgF
Direct:
Steady state WBC - release free radicals and inflammatory mediators
Increased risk of ACS in children with fever
ANC > 9
Hgb < 8.6
Previous ACS
URTI
Noncompliance to penicillin
Common infections causing ACS
C. pneumoniae
M. pneumoniae
RSV
Parvovirus B19 - marrow necrosis
Common cause of ACS
Pulmonary fat embolism - activates SPLA2 which liberates fatty acids, causing acute pulmonary toxicity
Wheezing in SCD
Increased risk of ACS, decreased lung function, death
ACS symptoms
Chest pain
Productive cough
Dyspnea
Bone pain if from fat embolism
Fever, tachypnea, crackles, wheezes
CXR of ACS
NEW PULMONARY INFILTRATE, commonly in lower and middle lobes
Presentation of SCLD
Hypoxemia
RLD due to recurrent damage to parenchyma
Cor pulmonale
Diffuse interstitial fibrosis in CXR
Risk factors for SDB/OSA in SCD
Compensatory adenotonsillar hypertrophy in functional asplenia
Altered facial bone structure due to extramedullary hematopoiesis
PFT in SCD
Obstructive becoming restrictive with age
Can be obstructive, restrictive, mixed
Causes of LFT abnormalities
- Asthma
- Hyperdynamic pulmonary circulation due to raised cardiac output from chronic anemia
- Transfusion causes increased pulmonary capillary blood volume
Diagnostics
Sickle test (HbS solubility test, sodium metabisulfite test)
Tests to separate hemoglobins
Molecular testing
Management of ACS
Broad spectrum antibiotics including atypicals
Hydration not more than 1.5x FM (can cause vascular leak)
Simple BT if low Hgb
Exchange transfusion if high Hct to avoid increased viscosity
Supplemental O2; escalate if increased hypoxia, dyspnea, pH < 7.25
Analgesia
Bronchodilator, dexamethasone
Inhaled NO if with PH
Management of PH in ACS
Anticoagulation
Hydroxyurea
Prostacyclin agonist or ET-1 antagonist NOT PDD5 inhibitor
LFT monitoring
Bronchodilator challenge if <70%
Cold air or exercise challenge if >70%
AVOID methacholine (can precipitate ACS)
Annual monitoring
Impulse oscillometry in young children
