CASE 1: Manipac Yao

1. The major cause his gastritis and gastric ulcer is the NSAID a non-selective COX-1 and COX-2 inhibitor.
2. Ibuprofen affects the synthesis of the two isoforms of PGH2 synthase which are COX-1 and COX-2.

COX-1 is essential for thromboxane formation in blood platelets, and for maintaining the integrity of the gastrointestinal
epithelium.
COX-2 is stimulated by growth factors, cytokines, and endotoxins.
- Inflammation is associated with the up-regulation of COX-2 and increased formation of prostaglandins. COX-2
levels increase in inflammatory disease states such as arthritis.
- Increased expression of COX-2 is seen in some cancer cells.
- It is also related to the expression of pain.

BIOCHEMICAL BASIS:

Cyclooxygenase is an enzyme which is essential to convert arachidonic acid to prostaglandins. Arachidonic acid is
converted to prostaglandin H2 in body with the help of enzyme cyclooxygenase. If the cyclooxygenase is inhibited by the
NSAID , there will be no formation of COX-1 and COX-2. COX-1 is needed to maintain the mucous secretion in the
stomach so that it will not be affected by the acid secretions. But since COX-1 is blocked therefore the mucous are not
secreted enough to help the stomach maintain its integrity therefore when the stomach pH is high the stomach will be
affected therefore ulcers and bleeding can occur, because the protective covering is lesser than is needed to protect it.

3. The patient can take COX-2 selective drugs like celecoxib, and etoricoxib.

CASE 2: Haya Lin

1. Respiratory distress syndrome (HYALINE MEMBRANE DISEASE) is one of the most common problems of
premature babies. It can cause babies to need extra oxygen and help breathing. The course of illness with
respiratory distress syndrome depends on the size and gestational age of the baby, the severity of the disease,
the presence of infection, whether or not the baby has patent ductus arteriosus, and whether or not the baby
needs mechanical help to breathe. (Children’s Hospital of Philadelphia)

Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most
commonly in those born at <37-week gestation. Risk increases with degree of prematurity. Symptoms and signs
include grunting respirations, use of accessory muscles, and nasal flaring appearing soon after birth.

Pulmonary surfactant is a mixture of phospholipids and lipoproteins secreted by type II pneumocytes. It diminishes the
surface tension of the water film that lines alveoli, thereby decreasing the tendency of alveoli to collapse and the work
required to inflate them. With surfactant deficiency, a greater pressure is needed to open the alveoli. Without adequate
airway pressure, the lungs become diffusely atelectatic, triggering inflammation and pulmonary edema. Because blood
passing through the atelectatic portions of lung is not oxygenated (forming a right-to-left intrapulmonary shunt), the
infant becomes hypoxemic. Lung compliance is decreased, thereby, increasing the work of breathing. In severe cases,
the diaphragm and intercostal muscles fatigue, and CO2 retention and respiratory acidosis develop.

CMMATIAS (CMED 2022)

 2. Biochemical basis

 Role of phosphatidylcholine in lung surfactant.

 Major constituents of surfactant are dipalmitoylphosphatidylcholine (DPPC or dipalmitoyl lecithin),

phosphatidylglycerol, apoproteins and cholesterol.

 These components normally contribute to a reduction in the surface tension within the air spaces (alveoli) of
the lung, preventing their collapse.

 Lung maturity of fetus can be gauged by determining the ratio of DPPC to sphingomyelin or the
Lecithin:Sphingomyelin or L:S ratio in amniotic fluid.

 L:S ratio value of 2 or more is evidence of lung maturity. An indication of a major shift from sphingomyelin to
DPPC synthesis that occurs in pneumocytes that occurs at about 32 wees of gestation.

3. SYMPTOMS

 Rapid, labored, grunting respirations appearing immediately or within a few hours after delivery, with
suprasternal and substernal retractions and flaring of the nasal alae. As astelectasis and respiratory failure
progress, symptoms worsen, with cyanosis, lethargy, irregular breathing, and apnea.

 Neonates weighing <1000g may have lungs so stiff that they are unable to initiate or sustain respirations in
the delivery room.

 On examination, breath sounds are decreased. Peripheral pulses may be decreased with peripheral
extremity edema and decreased urine output.

DIAGNOSIS

 Clinical presentation, including recognition of risk factors, ABGs showing hypoxemia and hypercapnia; and
chest x-ray. Chest x-ray shows diffuse atelectasis classically described as having a ground-glass appearance
with visible air bronchograms; appearance correlates loosely with clinical severity.
RDS can be anticipated prenatally using tests of fetal lung maturity, which are done on amniotic fluid obtained by
amniocentesis or collected from the vagina (if membranes have ruptured) and which can help determine the optimal
timing of delivery. These are indicated for elective deliveries before 39 wk when fetal heart tones, human chorionic
gonadotropin levels, and ultrasound measurements cannot confirm gestational age and for nonelective deliveries
between 34 wk and 36 wk.

Amniotic fluid tests include the

 Lecithin/sphingomyelin ratio
 Foam stability index test (the more surfactant in amniotic fluid, the greater the stability of the foam that forms
when the fluid is combined with ethanol and shaken)
 Surfactant/albumin ratio

Risk of RDS is low when lecithin/sphingomyelin ratio is > 2, phosphatidyl glycerol is present, foam stability
index = 47, or surfactant/albumin ratio is > 55 mg/g.

4. PREVENTION

CMMATIAS (CMED 2022)

  When a fetus must be delivered between 24 wk and 34 wk, giving the mother 2 doses of betamethasone 12
mg IM 24 h apart or 4 doses of dexamethasone 6 mg IV or IM q 12 h at least 48 h before delivery induces
fetal surfactant production and reduces the risk of RDS or decreases its severity.
 Prophylactic intratracheal surfactant therapy given to neonates who are at high risk of developing RDS
(infants < 30 wk completed gestation especially in absence of antenatal corticosteroid exposure) has been
shown to decrease risk of neonatal death and certain forms of pulmonary morbidity (eg, pneumothorax).

TREATMENT

 Intratracheal surfactant
 Supplementary oxygen as needed
 Mechanical ventilation as needed

Specific treatment of RDS is intratracheal surfactant therapy. This therapy requires endotracheal intubation, which
also may be necessary to achieve adequate ventilation and oxygenation. Less premature infants (those> 1 kg) and
those with lower oxygen requirements (fraction of inspired oxygen [FIO2] < 40 to 50%) may respond well to
supplemental oxygen alone or to treatment with nasal continuous positive airway pressure. A treatment strategy of
early (within 20 to 30 min after birth) surfactant therapy is associated with significant decrease in duration of
mechanical ventilation, lesser incidence of air-leak syndromes, and lower incidence of bronchopulmonary dysplasia.

Surfactant hastens recovery and decreases risk of pneumothorax, interstitial emphysema, intraventricular
hemorrhage, bronchopulmonary dysplasia, and neonatal mortality in the hospital and at 1 yr. However, neonates
who receive surfactant for established RDS have an increased risk of apnea of prematurity. Options for surfactant
replacement include

 Beractant
 Poractant alfa
 Calfactant
 Lucinactant

Beractant is a lipid bovine lung extract supplemented with proteins B and C, colfosceril palmitate, palmitic acid, and
tripalmitin; dose is 100 mg/kg q 6 h prn up to 4 doses.

Poractant alfa is a modified porcine-derived minced lung extract containing phospholipids, neutral lipids, fatty acids,
and surfactant-associated proteins B and C; dose is 200 mg/kg followed by up to 2 doses of 100 mg/kg 12 h apart
prn.

Calfactant is a calf lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated
proteins B and C; dose is 105 mg/kg q 12 h up to 3 doses prn.

Lucinactant is a synthetic surfactant with a pulmonary surfactant protein B analog, sinapultide (KL4) peptide,
phospholipids, and fatty acids; dose is 175 mg/kg q 6 h up to 4 doses.

Lung compliance can improve rapidly after therapy. The ventilator peak inspiratory pressure may need to be
lowered rapidly to reduce risk of a pulmonary air leak. Other ventilator parameters (eg, FIO2, rate) also may need to
be reduced.

CMMATIAS (CMED 2022)