CASE PRESENTATION

jood, 4year old, Saudi, Female

Admitted on 23.12.2010 Complaining of fever& cough &s.o.b &vomiting for 1 day

History of Present Illness :

Patient known case of chronic lung disease with pulmonary hypertension and dysplastic lungs on lasix 1mg/kg p.o o.d . Aldactone 1mg /kg p.o o.d and IIloprost 20mcg inhalation qid doing f .up in K.F.S.H Riyadh Patient was discharge 1 day before from almoasa H.was admitted with chest infection No history of chocking, or cyanosis, No history of F.B inhalation

Birth History : Product of uneventful pregnancy FT, SVD with birth wt. 3.2 kg NICU admission FOR 4 month with R.D /PDA LIGATED AT 3 weeks OF age/02 dependent for more than 3 month
Developmental History : delayed because sick most of the time

Nutritional History : On normal family food

Past History :

Multiple admission before with chest infection No previous hospitalization in R. C.hospital

Vaccination history : completed Family history : history of 2nd degree consanguinity no history of similar condition F.History of joints hyper mobility her uncle and 1cousin

examination

Conscious alert looks unwell no cyanosis with moderate respiratory distress with tachypnea with intercostals & sub costal recession well per fused well hydrated no dysmorphic feature * vital signs temp 39 c , H.R 170/min , R.R 65/min , spo2 87/.

Growth parameter weight 14.2 kg 10th centile height 10th centile head circumference normal * chest bilateral decrease air entry more in the left side with bilateral rhonchi & creps * heart s1 normal increased intensity of 2nd heart sound , no murmur , j.v.p not raised

Abdomen no distension sot &lax & no hepatomegaly , no organomegaly * C.N.S no deficit *joints hyper mobility ,no dislocation *skin hyper elasticity , no ecchymosis ,no other abnormality

Joint Hypermobility ability to painlessly perform one of the following maneuvers:

1. Extend the 5th metacarpophalangeal joint more than 90 degrees, oppose the thumb to the forearm (picture 1).

Bend her thumbs to her forearm.

2.

Extend the elbow more than 10 degrees beyond neutral (picture 2)

Investigation C.B.C 31.7 , HB 11.8 , platelets 255 ,neu 82.4 /. *C.R.protien 405mg/l * blood gas PH 7.35 mmol/l , pco2 33mmhg ,po2 63 mmhg ,Hco3 19.3 * chemistry normal

Admit Assessment

dysplastic left lung with multiple emphysematous change on left side O2 dependent with increase o2 requirement kept on o2 4 lit maintained o2 between 90 to 92 blood gas normal Febrile with moderate respiratory distress chest decrease air entry especially on the left side with inspiratory creps and rhonchi chest x ray showed pneumonic patches / CBC leucocytosis WBC 31000 started on iv antibiotics rocephin and vancomycin

Admission Assessment

Bronchospasm started on ventolin and pulmicort nebulization and methylprednisolone iv Pulmonary HTN kept in aldactone 1 mg /kg p.o O.D lasix 1 mg /kg b.d and IIOPROST 20 mcg inhalation QID

Admission ASSESSMENT

PATIENT ASSESED FOR hypermobility of joints and skin hyperelasticity

Hospital Course
Patient was admitted in picu initially for 3 days for close observation her respiratory distress improved shifted to regular room her fever subsided chest crepitation and rhonchi improved after 3days her C.B.C repeated her w.b.c 9.5 , c.r.protien came down after 2 days 124.3mg/l antibiotics completed for 10 days i.v patient discharge home in good condition o2 1 liter maintained spo2 95/ .

*lasix 1 mg /kg p.o once daily aldactone1 mg/kg o.d *prostin 20mcg inhaler q 10 *flexotide 125 mcg inhaler *OPD appointment after 1 week

Chronic lung disease

O2 dependent for more than 28 days or 36 weeks corrected gestational age with x ray change *causes of chronic lung disease multiple 1, prematurity with R.D.S 2,heart disease e.g. patent ductus arteriosus 3,persistant pulmonary hypertension of the new born 4* infection and others

Chronic lung disease is frequently complicated development of 2ry pulmonary hypertension which associated with increased morbidity &mortality hypoxia& infection

Causes of pulmonary hypertension

Ordinarily, the blood flows easily through the vessels in the lungs, so the blood pressure is usually much lower in the lungs. With pulmonary hypertension, the rise in blood pressure is the end result of a process that begins with changes in the cells that line the lungs' arteries. These changes cause the formation of extra tissue that eventually narrows or completely blocks the blood vessels. Scarring (fibrosis) usually also occurs, making the arteries stiff and narrow. This makes it harder for blood to flow, raising the pressure in the pulmonary arteries.

Classification
Group 1 PAH Examples: "Pulmonary arterial hypertension".

1. Idiopathic (IPAH) 2. Familial (FPAH) 3. Associated with (APAH):

Collagen vascular disease Congenital systemic-to-pulmonary shunts Portal hypertension HIV infection Drugs and toxins Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy) Pulmonary veno-occlusive disease (PVOD) Pulmonary capillary hemangiomatosis (PCH)

4. Associated with significant venous or capillary involvement

5. Persistent pulmonary hypertension of the newborn

Classification

Group 2 PH "Pulmonary venous hypertension". Examples:

1. Left-sided atrial or ventricular heart disease 2. Left-sided valvular heart disease

Group 3 PH "Pulmonary hypertension associated with disorders of the respiratory system or hypoxemia". Examples:

1. 2. 3. 4. 5. 6.

Chronic obstructive pulmonary disease Interstitial lung disease Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Development abnormalities

Classification

Group 4 PH "Pulmonary hypertension caused by chronic thrombotic or embolic disease". Examples:

1. Thromboembolic obstruction of proximal pulmonary arteries 2. Thromboembolic obstruction of distal pulmonary arteries 3. Non-thrombotic pulmonary embolism (tumor, parasites, foreign material)

Group 5 PH These patients have PH caused by inflammation, mechanical obstruction, or extrinsic compression of the pulmonary vasculature (eg, sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels by adenopathy, and fibrosing mediastinitis).

Signs and Symptoms

Most patients with PH initially experience exertional dyspnea, lethargy, and fatigue, which are due to an inability to increase cardiac output with exercise. As the PH progresses and right ventricular failure develops, exertional chest pain (ie, angina), exertional syncope, and peripheral edema may develop. In most circumstances, angina is due to subendocardial hypoperfusion caused by increased right ventricular wall stress and myocardial oxygen demand. However, angina can also be caused by dynamic compression of the left main coronary artery by an enlarged pulmonary artery; this risk is greatest for patients with a pulmonary artery trunk at least 40 mm in diameter

Physical Exam

The initial physical finding of PH is usually increased intensity of the pulmonic component of the second heart sound, which may even become palpable. The second heart sound is narrowly split or single in patients with PH and preserved right ventricular function. Splitting of the second heart sound widens as the right ventricle fails or if right bundle branch block develops. Auscultation of the heart may also reveal a systolic ejection murmur and, in more severe disease, a diastolic pulmonic regurgitation murmur. The right sided murmurs and gallops are augmented with inspiration. Right ventricular hypertrophy is characterized by a prominent A wave in the jugular venous pulse, associated with a right-sided fourth heart sound, and either a left parasternal heave or a downward subxiphoid thrust.

Physical Exam

Right ventricular failure results in systemic venous hypertension. This can lead to a variety of findings such as elevated jugular venous pressure, a right ventricular third heart sound, and a high-pitched tricuspid regurgitant murmur accompanied by a prominent V wave in the jugular venous pulse if tricuspid regurgitation is present. In addition, hepatomegaly, a pulsatile liver, peripheral edema, and ascites may exist. Some patients with PH due to severe COPD develop edema even in the absence of right heart failure. The pathogenesis of edema in such patients is not well understood. It has been hypothesized that edema may develop in these patients due to hypercapnia or hypoxemia. Hypercapnia is associated with an appropriate increase in proximal bicarbonate reabsorption, which minimizes the fall in arterial pH. This increase in proximal bicarbonate transport also promotes the passive reabsorption of sodium chloride and water, and may contribute to edema formation.

Complications

Right-sided heart failure (cor pulmonale). In this condition, your heart's right ventricle becomes enlarged and has to pump harder than usual to move blood through narrowed or blocked pulmonary arteries. Initially, the heart tries to compensate by thickening its walls and expanding the chamber of the right ventricle to increase the amount of blood it can hold. But this measure works only temporarily, and eventually the right ventricle fails from the extra strain. Blood clots. Clots are the end result of a complex process that helps stop bleeding after you've been injured. But sometimes clots form where they're not needed. A number of small clots or just a few large ones can lead to pulmonary hypertension, which is reversible with time and treatment. Having pulmonary hypertension makes it more likely you'll develop clots in the small arteries in your lungs, which is dangerous if you have narrowed or blocked blood vessels.

Arrhythmia. Irregular heartbeats from the upper or lower chambers of the heart are complications of pulmonary hypertension. These can lead to palpitations, dizziness or fainting and can be fatal. Bleeding. Pulmonary hypertension can lead to bleeding into the lungs and hemoptysis.

Generalized Treatment

Diuretics Diuresis will diminish hepatic congestion and peripheral edema. However, it should be performed with caution to avoid decreased cardiac output (due to decreased right and/or left ventricular preload), arrhythmias induced by hypokalemia, and metabolic alkalosis (which can depress ventilation). Although less common, fluid can also be removed by dialysis or ultrafiltration.

Oxygen therapy Continuous oxygen administration remains the cornerstone of therapy in patients with group 3 PH. It is inferred that oxygen may benefit other groups of patients with PH plus resting, exerciseinduced, or nocturnal hypoxemia. Oxygen should be considered for all patients with pulmonary hypertension plus hypoxemia. The flow of oxygen needed to correct hypoxemia should be determined by measurement of the oxygen saturation with therapy. Most often oxygen is administered at 1 to 4 L/min via nasal prongs and adjusted to maintain the oxygen saturation above 90 percent at rest and, if possible, with exercise and sleep. Supplemental oxygen will not significantly improve the oxygen saturation of patients with congenital heart disease and right-to-left shunt (Eisenmenger physiology).

Generalized Treatment

Exercise Exercise training improved the WHO functional class of PH and peak oxygen consumption. Despite the functional benefits, exercise training did not improve hemodynamic measures (eg, the pulmonary artery systolic pressure). Studies suggests that skeletal muscle training may play a major role in the treatment of patients with PH. Transplantation. In some cases, a lung or heart-lung transplant may be an option, especially for younger people who have idiopathic pulmonary hypertension. Major risks of any type of transplantation include rejection of the transplanted organ and serious infection, and you must take immunosuppressant drugs for life to help reduce the chance of rejection.

Advanced Therapy

Most pharmacologic agents used to treat PH promote vasodilation and are antiproliferative. These include prostanoids (eg, epoprestenol, treprostinil, and iloprost), endothelin receptor antagonists (eg, bosentan), and phosphodiesterase-5 (PDE5) inhibitors (eg, sildenafil). Calcium channel blockers (primarily nifedipine) are also used but benefit only a small minority patients. Their limited benefit may reflect the fact that CCBs are pure vasodilators without antiproliferative effects and vasoconstriction is rarely the predominant abnormality. General approach Patients with PH should undergo an invasive hemodynamic assessment and an acute vasoreactivity test prior to the initiation of advanced therapy. Patients with a positive vasoreactivity test can be given a trial of oral CCB therapy. In contrast, patients with a negative vasoreactivity test require advanced therapy with a prostanoid, endothelin receptor antagonist, or PDE5 inhibitor. Combination advanced therapy may be appropriate in truly refractory cases, although data are limited. Lastly, some patients will be refractory to all medical interventions. In these cases, lung transplantation or creation of a right to left shunt by atrial septostomy may be considered.

Advanced Therapy

Epoprostenol (FLOLAN) It improves hemodynamic parameters, functional capacity, and survival in patients with IPAH. In patients with other types of group 1 PAH, intravenous epoprostenol improves hemodynamic parameters and functional capacity. Epoprostenol should be considered the first-line agent in patients with severe disease (ie, NYHA class IV), and in less severe disease (ie, NYHA class II or III). Epoprostenol is delivered continuously through a permanently implanted central venous catheter using a portable infusion pump. It is usually initiated at doses of 1 to 2 ng/kg per min and increased by 1 to 2 ng/kg per min every one to two days as tolerated. Once an initial level of 6 to 10 ng/kg per min is achieved (usually within one to two weeks), most patients require dose increases of 1 to 2 ng/kg per min every two to four weeks to sustain the clinical effect. A maximal dose has not been established. Patients who have been receiving therapy for many years may receive doses as high as 150 to 200 ng/kg per min with sustained clinical and hemodynamic benefit. Excess doses may produce high output cardiac states. In this situation, the dose should be reduced, while monitoring for rebound pulmonary hypertension. Adverse effects. Side effects include jaw pain, diarrhea, and arthralgias. More severe adverse effects are usually attributable to the complex delivery system including thrombosis, pump malfunction, and interruption of the infusion. Central venous catheter infection can also contribute to the morbidity and mortality of continuous epoprostenol therapy.

Endothelin receptor antagonists Endothelin-1 is a potent vasoconstrictor and smooth muscle mitogen. High concentrations of endothelin-1 have been recorded in the lungs of patients with both IPAH and other etiologies of group 1 PAH including scleroderma and congenital cardiac shunt lesions. Bosentan Bosentan (Tracleer), a nonselective endothelin receptor antagonist, improves hemodynamics and exercise capacity in patients with group 1 PAH and delays clinical worsening. The mortality of bosentan-treated IPAH patients appears favorable. The major advantage of bosentan is its oral administration. The main adverse effect of bosentan therapy is hepatotoxicity, which appears to be more severe at higher doses. Liver function tests should be closely monitored during therapy and bosentan should not be used in patients with moderate or severe hepatic dysfunction, or in conjunction with cyclosporine or glyburide. It is also a potent teratogen; meticulous contraception is required if bosentan is used by women with childbearing potential.

Advanced Therapy

Selective

agents Sitaxsentan and ambrisentan are selective type A endothelin-1 receptor antagonists that are administered orally. Preliminary data suggest that they improve exercise tolerance, WHO functional class, hemodynamics, and quality of life in patients with PAH. While there exist theoretical advantages to selective inhibition of the type A endothelin-1 receptor, no clinical advantage to selective inhibition has been demonstrated over nonselective inhibition. The selective agents are also associated with hepatotoxicity and require frequent monitoring of liver function tests.

Advanced Therapy

PDE inhibitors Sildenafil (Viagra, Revatio) is an orally administered cyclic GMP phosphodiesterase type 5 (PDE5) inhibitor that prolongs the vasodilatory effect of nitric oxide. Sildenafil improves pulmonary hemodynamics and exercise capacity in patients with group 1 PAH. And sildenafil is associated with improved arterial oxygenation. Combination therapy Limited experience suggests that bosentan (TRACLEER) can be used safely and effectively with epoprostenoL (FLOLAN) or treprostinil (REMODULIN). The benefits of bosentan plus sildenafil (REVATIO) are best described in patients with IPAH, . Several small trials combining inhaled iloprost (VENTAVIS) and oral sildenafil (REVATIO) have reported improved outcome with combination therapy.

Causes of hyper mobility of joints * misaligned joints * abnormal shaped ends of one or more bones at a joint * a type 1 collagen or other connective tissue defect found in ehler danlos syndrome and marfan syndrome * abnormal joints prioception the condition runs in families suggest that may be a genetic basis

For many people joint hypermobility is relatively benign, but for some people it is the most apparent sign of a rare connective tissue disorder called

Ehlers-Danlos Syndrome.

EDS - Overview
Ehlers-Danlos is a Connective Tissue Disorder caused by defective collagen, the glue that holds the body together. Who is effected?

1 in 5,000 to 10,000 people Males and females equally All ethnic backgrounds

Three common types - Hypermobile, Classic, and Vascular

Similar symptoms, effecting skin and joints Different genetic mutations Runs true in families Vascular EDS is the only type that is life threatening

EDS Signs and Symptoms

Joints

Hypermobile loose or unstable Prone to dislocations and subluxations Chronic joint pain/ Early onset arthritis

Bend his little fingers back to 90-degree angle. (1 Point for each finger.)

Keep knees straight, bend forward and touch the ground with hands flat. (1
Point)

Extend her elbows beyond 10-degrees

Extend her knees beyond 10-degrees. (1 Point).

4. Place both palms on the floor without bending the knees (picture 4).

EDS Signs and Symptoms

Skin
Soft, velvety to the touch Hyperextensive Fragile tears and bruises easily Slow wound healing Scars widen over time Fleshy lesions Diagnosis by skin biopsy ,DNA,biochemical studies but all not sensitive to identify all cases

EDS In the Classroom

Create a safe environment

Avoid slippery floors carpeting is preferable Ergonomic furniture adjusted to correct height Use elevator instead of stairs Lockers at mid-level

Finger joints may be weak

Poor fine motor skills May need help with note-taking

Pencil grips may be helpful

May need additional time for taking tests

EDS In the Classroom

Ehlers-Danlos is a life-long condition and is considered a disability under Section 504 of the Rehabilitation Act of 1973. At school, primary concerns:

Emergency Plan Avoiding injury Preserving joints Emotional considerations