DUYGU UNKARACALAR, PGY-1

02/03/2010

Diarrhea started 4 weeks ago, green, watery, non-bloody, (+) mucus x4/day

x2-3/day vomiting after feeds for about 3-4 weeksNo feverRecently less active, sleepy but sometimes irritableNo URI symptomsDecrease UOP (last 5 days x1 wet diaper/day but

mother does not know if he passes urine with diarrhea)

No travel hx or sick contacts

Chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days

Mechanism:Osmotic diarrhea (common in children)Secretory diarrheaMotility disturbancesInflammatory

Vomiting and diarrhea are common in infants and are most often infectious. If persists >1 week, intolerance of formula or some other protein should be suspected Diet history

Infection Formula intolerance

Mucosal injury

Increase permeability

Further Exacerbated formula intolerance

mucosal injury

Malabsorption, poor intake

Malnutrition

Diet: Breast milk only every 3 hours for 20 mins, no change in appetite

PMH:BH FT, NSVD, Apgars: 9/9, no NICU BW: 2560 gNo similar problems before, no medical problemsNo surgery or hospitalizationsNKDA, UTD

FH: 22 y/o Mother & Father, healthy, no consanguinity, no previous pregnancy

SH: First and only child lives with parents

Looks pale and tiredT: 37.6, HR: 158, RR: 38, BP: 90/45, sO2: 97%Wt: 3200 (<3 pc), Ht: 55 cm (3-10 pc), HC: 38 cm ( <3 pc)HEENT: NCAT, depressed anterior fontanel, sunken eyes,

dry mucous membranes, dry lips, op wnl, Tms wnl, no LAPsLungs: B/L equal air entry, no w/r/rHeart: (+) S1, S2, no MAbd: Distended, (+) BS, NTND, 3 cm palpable liver, no SMExt: Cap refill =4-5 sec, B/L weak pulses , 2+ pretibial edemaGenital: Tanner stage I male, testes b/l in scrotumSkin: No rash, delayed turgor-tonus Neuro: Alert, able to hold his head when prone, no

lateralizations, DTRs b/l equal, moro (++/++), grasping (++/++)

GI: Formula protein

intolerance/allergy Intractable diarrhea-like

syndrome Malabsorption Syndromes

Cystic fibrosis Shwachman-Diamond

Syndrome Disorders of liver and biliary

tract Congenital lactase deficiency Glucose-galactose

malabsorption Sucrase-isomaltase deficiency Intestinal enterokinase

deficiency Short bowel syndrome Hirsprung disease Autoimmun entheropathy Acquired lactose intolerance

Infectious: Giardiasis Protracted viral enteritis Intestinal protozoal diseases

Systemic: Crohn’s disease Hyperthyroidism Immune deficiencies ( IgA

deficiency)

CBC: 16.1 > 7.1/ 21 < 70, retic: 1%Periferal smear: 58 % PMNL, 40% L, 2% MU/A: pH: 5, SG: 1021, (+) bil, rare leucocytesBMP: 129/4.9, 101/17, 4/0.12, 128/9.28, PO4: 4.83LFT: 3.67/2.01, 95/67, 309/439, 3.22/2.29PT: 15.4, INR: 2, APTT: 45Stool guiac (-) Stool cx Pending, stool parasitis PendingBlood cxPendingVitamin A, D, E & K blood levelsPendingIg A, M, G levels Pending

IVF, Vitamin K, FFP, RBC transfusionsSulbactam-Ampicillin + Amikacin2nd day : T: 38.3, dry cough CXR: hyperinflation,

no infiltrationStool pH: 6, reducing substance (-), stool Fat (-)Stool cx (-), stool parasitis x3 (-), Blood cx(-) Stool guiac x3 (-)Low vitamin A & E blood levelsIg A, M, G levels wnl

Increase LFTs

? Cystic Fibrosis

Malabsorption

Sweat test: 97 mEq/l

The most common lethal inherited disease in the caucasians

An autosomal recessive disorderA disease of exocrine gland function that involves

multiple organ systems Chronic respiratory infections, pancreatic enzyme

insufficiency and associated complicationsMedian survival age-36.9 years

Mutations in the CFTR gene

Protein (Cl channel-CAMP)

Decrease secretion of Cl + increase reabsorb of Na&wateracross the epithelial cells

Increased viscosity of secretions makes them difficult to clear (respiratory tract, pancreas, GI tract, sweat glands

and other exocrine tissues)

Most fatalities associated with progressive lung disease The lungs are normal in utero, at birth, and after birth, before the

infection Shortly after birth, many patients acquire a lung infection

(Haemophilus influenzae, Staphylococcus aureus, P aeruginosa, Burkholderia cepacia, Escherichia coli, and Klebsiella pneumoniae)

Clinical picture:Chronic or recurrent cough Prolonged symptoms of bronchiolitis occur in infants Posttussive vomiting episodes Recurrent wheezingRecurrent pneumoniaAtypical asthmaPneumothoraxHemoptysisDigital clubbing Dyspnea on exertionHistory of chest painRecurrent sinusitisNasal polyps

Intestinal Neonates:

Infants may present with intestinal obstruction at birth Meconium ileus (7-10%)VolvulusIntestinal atresiaPerforationMeconium peritonitisPassage of meconium may be delayed (>24-48 h after

birth)Cholestatic jaundice may be prolonged

Infants and children: Increased frequency of stools Malabsorption (ie, fat in stools, oil drops in stools)Failure to thriveIntussusception (ileocecal)Rectal prolapse

PancreaticPancreatic insufficiency (PI)

Fat-soluble vitamin deficiency Malabsorption of fats, proteins, and carbohydrates (Steatorrhea,

frequent, poorly formed, large, bulky, foul-smelling, greasy stools that float in water)

Failure to thrive (despite an adequate appetite)Foul-smelling flatusRecurrent abdominal painAbdominal distentionMany infants have symptoms of gastroesophageal reflux

HepatobiliaryGallstonesJaundiceHepatosteatosis, obstructive cirrhosis Gastrointestinal tract bleeding

Males are frequently sterile because of the absence of the vas deferens

Undescended testicles Hydrocele Fertility is maintained, although possibly

decreased, in femalesSecondary sexual development is often

delayedAmenorrhea may occur in patients with severe

nutritional or pulmonary involvement

Sweat testThe quantitative pilocarpine iontophoresis test (QPIT) to

collect sweat and perform a chemical analysis of its chloride content

>60 mmol/L of chloride in the sweat RepeatFalse (+) results

Genetic test (>1600 CF mutations, ΔF508)Neonatal screening: Rely on testing for immunoreactive

trypsinogen (IRT). The presence of high levels of IRT, a pancreatic protein typically elevated in infants with cystic fibrosis. If (+), repeat IRT testing, DNA testing, or both.

CXR: Hyperinflation, peribronchial thickening, bronchiectasis , pulmonary nodules resulting from abscesses, infiltrates, atelectasis, flattenned domes of the diaphragm, thoracic kyphosis, and bowing of the sternum, pulmonary artery dilatation and right ventricular hypertrophy associated with cor pulmonale. Several radiologic scoring systems are recognized

Sinus Radiography: Panopacification of the sinuses is present in almost all patients with cystic fibrosis

(high sensitivity and specificity)

Pulmonary function testing (PFT)Obstructive changes in the beginningRestrictive changes

Semen analysisObstructive azospermi

Bronchoalveolar lavage

Sputum microbiology

Controlling respiratory infection, clearing airways of mucous, administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral supplements) to maintain adequate growth, and managing complications

Multidisciplinary carePatient/parent education, including counselingA high-energy and high-fat diet, in addition to vitamin

(especially fat soluble) and mineral supplementationUpper body exercises, such as canoe paddling, may

increase respiratory muscle endurance

Pancrelipase (Creon, Pancrease, Ultrase, Viokase)

Enteric-coated pancreatic enzyme microspheres containing various amounts of lipase, protease, and amylase. Assists in digestion of protein, starch, and fat

Vitamins A, D, E, and K Agents to treat associated conditions or complications

(eg, insulin) BronchodilatorsMucolytic agents (Dornase alfa)Antibiotics

Cephalosporins-H. inf, Staph. Aureus, Pseu. AureginosaFlouroquinolones-P. aureginosaAerosolized form (eg, gentamicin, colistin, tobramycin)

Every 2-3 months to achieve the following goals: Maintenance of growth and development Maintenance of as nearly normal lung function as

possibleAppropriate use of antibiotics, bronchodilators, and

airway clearance techniques Clinical assessment to monitor gastrointestinal tract

involvement and presence of malabsorption and to provide enzyme and nutrition supplementation

Monitoring for complications and their treatment Addressing psychosocial issues

Nasal polyps Chronic and persistent

sinusitis with complications such as mucopyocele formation

Bronchiectasis Atelectasis Pneumothorax Hemoptysis Hypertrophic pulmonary

osteoarthropathy Allergic bronchopulmonary

aspergillosis (ABPA) Pulmonary hypertension Cor pulmonale End-stage lung disease Osteoporosis

Pancreatitis Cystic fibrosis–related

diabetes mellitus Meconium ileus Distal intestinal obstruction

syndrome Gastroesophagial reflux Rectal prolapse Vitamin deficiency (especially

fat-soluble vitamins) Fatty liver Focal biliary cirrhosis Portal hypertension Liver failure Cholecystitis and

cholelithiasis Rickets

Creon 3000 U/kg, multivitamin & minerals, continue IVF and antibiotics

Decrease sO2 78-80%ABG: pH: 7.28, pCO2: 66 Intubation PICUMeropenem & Vancomycin8th day of admission Multiple organ failure DeathHomozygotic ΔF508 mutation (+)Genetic counselling

Full autopsy was doneLungs: Macroscopically massive consolidations, intraalveolar

macrophages, mononuclear infectious cell infiltration in the interstitial tissue, patchy intraalveolar hemorrhage, cx Stenotrophomonas maltophilia, Acinetobacter lwoffii

Liver: Bigger than regular size (281 g-N: 143 g), hepatosteatosis, cholestasis, mild mononuclear inflamatuar cell infiltrations in some portal areas

Spleen: Bigger than regular size (21 g-N:15g), severe congestion

Pancreas: Fibrosis, ductal dilatation, eosinophilic material in the lumens

Brain: Mild edemaOthers: Congestion

Davis PB, Drumm M, Konstan MW. Cystic fibrosis. Am J Respir Crit Care Med. Nov 1996;154(5):1229-56. 

Collaco JM, Vanscoy L, Bremer L, et al. Interactions between secondhand smoke and genes that affect cystic fibrosis lung disease. JAMA. Jan 30 2008;299(4):417-24. 

Sharma GD, Doershuk CF, Stern RC. Erosion of the wall of the frontal sinus caused by mucopyocele in cystic fibrosis. J Pediatr. May 1994;124(5 Pt 1):745-7.

Bruno MJ, Haverkort EB, Tytgat GN, van Leeuwen DJ. Maldigestion associated with exocrine pancreatic insufficiency: implications of gastrointestinal physiology and properties of enzyme preparations for a cause-related and patient-tailored treatment. Am J Gastroenterol. Sep 1995;90(9):1383-93. 

LeGrys VA, Yankaskas JR, Quittell LM, Marshall BC, Mogayzel PJ Jr. Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr. Jul 2007;151(1):85-9.

[Guideline] Comeau AM, Accurso FJ, White TB, et al. Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report. Pediatrics. Feb 2007;119(2):e495-518.

Goulet O, Ruemmele F. Causes and management of intestinal failure in children. Gastroenterology. 2006;130 (2 Suppl 1):S16-28. 

Ren CL, Brucker JL, Rovitelli AK, Bordeaux KA. Changes in lung function measured by spirometry and the forced oscillation technique in cystic fibrosis patients undergoing treatment for respiratory tract exacerbation. Pediatr Pulmonol. Apr 2006;41(4):345-9. 

[Best Evidence] Moran A, Pekow P, Grover P, et al. Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy trial. Diabetes Care. Oct 2009;32(10):1783-8.