Paediatrics State Exam Questions 2023-2024 PDF

PEDIATRICS STATE EXAM UPJS 2023-2024  STATE EXAM QUESTIONS - Paediatrics 1. Pneumonia in Infants and Toddlers Differential Diagnosis of Nonconjugated Hyperbilirubinemia Side Effects of Longterm Treatment with Corticosteroids and Prevention’...

PEDIATRICS STATE EXAM UPJS 2023-2024  STATE EXAM QUESTIONS - Paediatrics 1. Pneumonia in Infants and Toddlers Differential Diagnosis of Nonconjugated Hyperbilirubinemia Side Effects of Longterm Treatment with Corticosteroids and Prevention’s Possibilities 2. Pneumonia in Older Children Differential Diagnosis of Conjugated Hyperbilirubinemia Cutaneous Infections in Children 3. Tuberculosis Differential Diagnosis of Nausea and Vomiting in Children Prematurity and Low Birth Weights Complications and Consequences 4. Bronchial Asthma Differential Diagnosis of Haematuria Defects in Metabolism of Carbohydrates (Galaktosemia, Fructose Disorders, Glycogenoses) 5. Cystic Fibrosis Differential Diagnosis of Proteinuria Primary and Secondary Immunodeficiencies (AIDS) 6. Acute Bronchitis and Bronchiolitis Differential Diagnosis of Oedema Vaccination - Principles, Schedule 7. Congenital Heart Diseases with Left to Right Shunt Differential Diagnosis of Unconsciousness Sinusitis, Tonsillitis and Adenoids 8. Congenital Heart Diseases with Right to Left Shunt Differential Diagnosis of Lymphadenopathy Neonatal Screening, Birth Trauma 9. Infective Endocarditis Hypoglycaemia in Children Juvenile Idiopathic Arthritis 10. Myocarditis and Pericarditis Seizures in Children Bone Diseases (Osteomyelitis, Aseptic Necrosis, Osteoporosis) 11. Dysrhythmias in Children Iron Deficiency Anaemias Adrenal Gland Cortex Diseases 12. Heart Failure and its Treatment Acute Leukaemias, Malign Lymphomas Primary Monosymptomatic Nocturnal Enuresis, Undescended Testis Department of Paediatrics and Adolescent Medicine Pavol Jozef Šafárik University in Košice, Faculty of Medicine  STATE EXAM QUESTIONS - Paediatrics 13. Arterial Hypertension Congenital and Acquired Coagulopathies Otitis Media, Mastoiditis, Hearing Screening 14. Upper and Lower Urinary Tract Infections Differential Diagnosis of Chronic Cough Numeric and Structural Anomalies of Autosomes and Gonosomes 15. Vesicoureteral Reflux and Obstructive Uropathy Congenital and Acquired Thrombocytopenias and Thrombocytopathies The Most Frequent Respiratory Complications in Term Neonates (RDS, PPNH, Transitory Tachypnea of Newborn, MAS) 16. Acute Kidney Injury, Haemolytic-Uremic Syndrome Differential Diagnosis of Syncope ALTE and Sudden Infant Death Syndrome 17. Chronic Kidney Disease (CKD) Principles and Indications of Formula Feeding, Formula Types Congenital Viral and Bacterial Newborn’s Infections (TORCH, GBS, E. coli) 18. Acute Poststreptococcal and Rapidly Progressive glomerulonephritis Breastfeeding, Complementary feeding and Weaning Acute Infectious Laryngitis, Acute Epiglottitis 19. Obesity in Childhood, Dyslipidaemias Differential Diagnosis of Hepatosplenomegaly Solid Tumours in Children (including Tumours of Central Nervous System) 20. Sepsis in Childhood Disorders of Thyroid Gland Acute Abdomen 21. Nephrotic Syndrome Fever and its Treatment, Fever of Unknown Origin (FUO) Disorders of Calcium and Phosphorus Metabolism, Disorders of Parathyroid Gland 22. Acid-Base Disorders Meningitis and Encephalitis Congenital Abnormalities of Digestive System 23. Oesophageal (GERD) and Stomach Disorders Vitamin D and K deficiency (rickets) Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Scleroderma Department of Paediatrics and Adolescent Medicine Pavol Jozef Šafárik University in Košice, Faculty of Medicine  STATE EXAM QUESTIONS - Paediatrics 24. Growth Disorders Chronic glomerulonephritis (IgA Nephropathy, Henoch-Schönlein Purpura), Alport Syndrome Antibiotic Therapy in Children 25. Acute Diarrhoea in Children Differential Diagnosis of Polydipsia and Polyuria Non-infectious Cutaneous Disorders in Children (Atopic Dermatitis, Urticaria, Seborrheic Dermatitis, Haemangiomas) 26. Inflammatory Bowel Disease in Children Diabetes Mellitus Type 1 Child Abuse and Neglect 27. Malabsorption and Celiac Disease Infant and Child Resuscitation Disorders of Amino Acid Metabolism (Phenylketonuria, Disorders of Ammonia Detoxification) 28. Disorders of Water Balance Scope and History of Pediatrics, Pediatric Epidemiology Cardiomyopathies 29. Malnutrition and Failure to Thrive Congenital Malformations of Central Nervous System Foreign Body Aspiration 30. Childs Growth and Development Anaemias (except for Iron Deficiency Anaemias) Liver Insufficiency, metabolic Disorders of Liver 31. Shock in children Differential diagnosis of Dyspnoe Disorders of Puberty 32. Disorders of Sodium and Potassium metabolism Differential diagnosis of Chest Pain Viral hepatitis and Chronic Hepatitis Department of Paediatrics and Adolescent Medicine Pavol Jozef Šafárik University in Košice, Faculty of Medicine 1a. Pneumonia in Infants and Toddlers Pneumonia: Definition: - “Pneumonia is an infection of the lower respiratory tract that involves the airways and parenchyma with consolidation of the alveolar spaces” - Lower RTI is often used to encompass bronchitis, bronchiolitis, pneumonia, or any combination of the three. - Lobar pneumonia describes pneumonia localized to one or more lobes of the lung - Atypical pneumonia describes patterns typically more diffuse or interstitial than lobar pneumonia. - Interstitial pneumonitis refers to inflammation of the interstitium, which is composed of walls of the alveoli, the alveolar sacs and ducts, and the bronchioles.It is characteristic of acute viral infections but may also be chronic inflammation. - Bronchopneumonia refers to inflammation of the lung that is centered in the bronchioles and leads to production of a mucopurulent exudate that obstruct some of these small airways and causes patchy consolidation of the adjacent lobules Epidemiology: - Immunization have had a great impact on the incidence of pneumonia caused by Pertussis, Diphtheria, Measles, Haemophilus, Influenza and S. pneumoniae - Risk factors for lower RTI include: o GERD, neurological impairment (aspiration), immunocompromising situations, anatomic abnormalities of respiratory tract, stay in hospital (ICU). Etiology: - Community-acquired pneumonia o Neonates: E. coli, S. agalactiae, S. pneumoniae o Infants: RSV, Herpes simplex, CMV, S. pneumoniae, H. influenzae o Toddlers: RSV, Parainfluenza, influenza viruses, human metapneumovirus, S. pneumoniae o Older children: Mycoplasma pneumoniae, S. pneumoniae, C. pneumoniae - Atypical pneumonia: o Mycoplasma pneumoniae o Chlamydophila pneumoniae - Afebrile pneumonia in infants: o Chlamydia trachomatis, Mycoplasma hominis, U. urealyticum, CMV - Pneumonia in immunocompromised patients: o Mycobacterium avium complex o Aspergillus o CMV o Pneumocystis jiroveci - Patients with cystic fibrosis: o S. aureus (in infancy) o P. aeruginosa, B. cepacia (older patients) Clinical manifestations: - Neonates: o May have fever or hypoxia only, with subtle or absent physical findings - Infants: o Apnea may be the first sign of pneumonia - Toddlers: o Fever, chills, tachypnea, cough, malaise, retractions, dyspnea are morecommon in older infants and children. - In general, viral pneumonias are associated more often with cough, wheezing, or stridor, but fever can be less prominent in viral pneumonia compared to bacterial. - Bacterial pneumonias typically are associated with higher fever, chills, cough, dyspnea, crackles on auscultation and concomitant conjunctivitis (infants) may be present. Typical respiratory symptoms: o Dyspnea, chest pain, cough (productive/non-productive) o Fever: ▪ During fever the HR will increase approx. 10 beats per 1 celsius o Tachypnea – the most sensitive and specific symptom of pneumonia ▪ Newborn: RR > 60 – indication of severe infection RR > 70 ▪ Infant: RR > 50 – indication of severe infection RR > 70 ▪ Toddler: RR > 40 – indication of severe infection RR > 50 ▪ Older child: RR > 20 – indication of severe infection RR > 50 o Associative symptoms: ▪ Abdominal pain, rash (viral infections), headache, lethargy,pharyngitis, nausea, vomiting, diarrhea ▪ Involvement of eye – think C. trachomatis o Signs of respiratory distress: ▪ Nasal flaring ▪ Intercostal and subcostal retractions ▪ Grunting o Clinical pictures: - Tachypnea + respiratory distress (in drawing) + stridor in child – Refer to hospital for ATB and O2 - Tachypnea – Non-severe pneumonia – Prescribe appropriate ATB - Normal respiratory rate - Advise caregiver Diagnosis: - History: o Immunization status? TB exposure? Maternal chlamydia/group B strepstatus? o Choking episodes (pneumonia following foreign body)? o Previous episodes of pneumonia? Previous antibiotics? o Travel history, animal exposure etc. - Basic parameters to be checked if suspicion of pneumonia: o RR, HR, Temperature, O2 saturation - Investigations (routine blood work is not required in children with uncomplicatedlower RTI who will be treated as outpatients): o CBC o CRP, PCT o Electrolytes, particularly sodium – severe pneumonia, complication of SIADH o Consider blood cultures, sputum cultures o TB testing - Auscultation: o Crackles – basally, bilateral or unilateral Every child less than 3 months with signs of pneumonia should be referred immediately to nearest healthcare facility because they are at high risk of severe illness: o In this cases, X-ray is mandatory (In older children it depends on the clinicalpicture) - CXR: o This is not indicated in children with mild, uncomplicated lower RTI who will be treated as an out-patient (children over 3 months) o Indication: ▪ Severe infections ▪ To exclude other pathology and look for complications ▪ To exclude pneumonia in an infant less than 3m o May confirm the diagnosis but cannot differentiate between viral and bacterial infection o Findings: ▪ Cavities containing fluid and air is charachteristic of staph. Pneumonia ▪ Patchy, peripheral consolidation – viral pneumonia ▪ Lobar consolidation – bacterial infection ▪ Perihilar infiltrates – mycoplasma infection ▪ Pleural effusion, emphysema – reveals complications o In case of serious disease, such as pleural abscess, ct chest can be utilized Treatment: - Supportive measures: o Adequate hydration, oxygenation, nutrition, antipyretics and pain control o Wheezing – rapid-acting bronchodilators o Fever – paracetamol - Monitoring should include: o RR, work of breathing, auscultation o Temperature o HR o O2 sat  - Criteria for intensive care: o O2 sat < 92 in FiO2 of > 0.6 o Shock o Rising respiratory rate and rising pulse rate with clinical evidence of severerespiratory distress and exhaustion, with or without a raised PaCO2 ▪ Respiratory failure: Low PO2 (type 1), Low PO2 + High PCO2 (type 2) o Recurrent apnea or slow irregular breathing - Antibiotics – dose according to child’s weight! o Antibiotics that are used depend on age of patient and etiology: ▪ Common antibiotics for treating pneumonia:  Oral antibiotics: o Amoxicillin, Amoxicillin-Clavulanate, Cotrimoxazole, Azithromycin, Clarithromycin, Erythromycin, Cefaclor  IV antibiotics o Amoxicillin, Ampicillin, Cefotaxime, Cefuroxime o Amoxicillin is DOC for outpatients o IV 3rd generation cephalosporins for inpatients ▪ In child less than 1 year o IV ampicillin or penicillin for inpatients ▪ In child over 1 year of age o Atypical pneumonia (most common in older children > 5 years) ▪ Macrolides Complications o Pleural effusion – fluid in the pleural space as the result of inflammation. o Empyema – bacterial infection in the pleural space. Parapneumonic effusions develop in approximately 40% of patients admitted to hospital with bacterial pneumonia. If an effusion is present and the patient is persistently febrile, the pleural space should be drained. o Necrotizing Pneumonia – necrosis or liquefaction of lung parenchyma. o Lung Abscess – A collection of inflammatory cells leading to tissue destruction resulting in one or more cavities in the lungs. A rare complication. Treatment of both Necrotizing Pneumonia and Lung Abscess involves long term parenteral antibiotics for 2-4 weeks, or 2 weeks after the patient is afebrile, and has clinically improved. o Hyponatremia: ▪ Serum sodium 5 mg/dl Children: >2-3 mg/dl Non-conjugated hyperbilirubinemia: - Physiological jaundice of the newborn - 1. Increased hemoglobin breakdown: o Hemolysis: ▪ G6PD deficiency ▪ Hemolytic disease of the fetus and newborn ▪ Sickle cell anemia, Spherocytosis, Thalassemia - 2. Impaired hepatic uptake of bilirubin o Drugs (e.g. rifampin, sulfonamides) - 3. Defective conjugation of bilirubin o Inherited hyperbilirubinemia ▪ Gilbert syndrome ▪ Crigler-Najjar syndrome o Neonatal jaundice ▪ Liver disease: ▪ Hepatitis (e.g. viral, toxic, autoimmune) ▪ Cirrhosis ▪ Wilson disease Physiological jaundice of the newborn: - Physiological jaundice of the newborn is a common cause of hyperbilirubinemia among newborns. It is a diagnosis of exclusion, made after careful evaluation has ruled out more serious causes of jaundice, such as hemolysis, infection, and metabolic disease. - Physiologic jaundice is the result of many factors that are normal physiologic characteristics of newborns, which include: o Increased bilirubin production resulting from an increased RBC mass o Shortened RBC life span o Hepatic immaturity of ligandin and glucuronosyltransferase - The clinical pattern of physiologic jaundice in term infants includes a peak indirect bilirubin level of no more than 12 mg/dL on day 3 of life. In premature infants, the peak is higher (15mg/dL) and occurs later (5th day). - The jaundice is non-physiological or pathological if it is clinically evident on the first day of life, if: o the bilirubin level increases more than 0.5mg/dL/hr o the peak bilirubin is greater than 13 mg/dL in term infants o the direct bilirubin fraction is greater than 1.5mg/dL o hepatosplenomegaly and anemia is present Increased hemoglobin breakdown: Glucose-6-phosphate dehydrogenase defi ciency: (Favism) - G6PD deficiency leads to an impaired regeneration of reduced glutathione, an important antioxidant, which makes RBCs more susceptible to oxidative stress andcan result in episodic hemolytic anemia. - The condition is inherited in an X-linked recessive pattern and it is the most common human enzyme deficiency worldwide. G6PD is the rate-limiting enzyme ofthe pentose phosphate pathway.  - The disease is usually asymptomatic, but a sudden surge in oxidative stress (e.g. infection, consumption of fava beans, or various drugs such as antimalarial, sulfa-drugs (TMP-SMX)) may lead to a life-threatening hemolytic crisis. These crises arises within 2-3 days after increased oxidative stress and presents with sudden onset of back or abdominal pain, jaundice, dark urine and possible transient splenomegaly. - G6PD deficiency is diagnosed based on intravascular hemolysis findings (e.g. normocytic anemia, increased LDH, increased reticulocyte count and decreased haptoglobin), as well as Heinz bodies and bite cells found in blood smears. The confirmatory test includes quantitative G6PD enzyme analysis. - Managed by preventing triggers of hemolysis.. Hemolytic disease of the fetus and newborn: Definition: - HDFN is a condition characterized by the destruction of fetal red blood cells and anemia. It is commonly caused by Rhesus and ABO incompatibility between motherand fetus. Etiology: - ABO incompatibility - Rhesus incompatibility - Risk factors: Maternal exposure to fetal blood during pregnancy (amniocentesis, termination of pregnancy, ectopic pregnancy, placental abruption) Pathophysiology: - ABO incompatibility o Highest risk: ▪ Mother, blood group O – child, blood group A or B ▪ Maternal antibodies (anti-A and/or anti-B) against non-self-antigens ofthe ABO system are present even if sensitization has not occurred - Rhesus incompatibility o In a Rh-negative mother and Rh-positive child: ▪ Maternal exposure to fetal blood → Production of maternal IgM antibodies against the Rh antigen → Over time, seroconversion toRh-IgG (able to cross placenta). In a subsequent pregnancy with aRh-positive child:  Rapid production of maternal IgG anti-D antibodies to fetal RhD antigens → Rh-IgG agglutination of fetal RBCs with hemolyticanemia → Risk of HDFN and hydrops fetalis Clinical features: - Prenatal – hydrops fetalis (only expected in cases of Rh incompatibility) - Postnatal – Neonatal anemia, hepatosplenomegaly, neonatal jaundice, hypoxiaDiagnosis: - Prenatal – imaging; ultrasound to determine hydrops fetalis, doppler sonography of fetal blood vessels to look for increased flow rate indicating fetal anemia - Postnatal – Coombs test: o In Rh incompatibility – positive o In ABO incompatibility – weak-positive or negative Treatment: - Prenatal: o Intrauterine blood transfusion - Postnatal: o Anemia – iron supplementation and RBC transfusion (if necessary) o Hyperbilirubinemia – phototherapy o In severe cases – IV immunoglobulin (IVIG) Prevention: - Screening:  ABO and Rh(D) typing of the mother: ▪ Rh-positive mothers do not need further screening ▪ Rh-negative mothers – screening for anti-D antibodies  Anti-D antibodies present (Sensitized mothers) → Monitoring for evidence of hemolysis (amniocentesis, imaging)  In cases of postpartum hemorrhage (in Rh-negative mother): 1. Conduct Rosette test – a qualitative test that assesses if fetal-maternal hemorrhage occurred. 2. If positive Rosette → Conduct Kleihauer-Betke test –a quantitative test for evaluation of fetal-maternal hemorrhage Defective conjugation of bilirubin: Gilbert syndrome: - inherited as an autosomal recessive trait - caused by mutations to the UGT1A1 gene located on the long arm (q) of chromosome 2 (2q37) - is characterized by a 70–80% reduction in the glucuronidation activity of the enzyme (UGT1A1) - may become apparent shortly after birth, it may not be recognized for many years - episodes of mild jaundice may appear in young adults and is more common in males than females, frequently, episodes of jaundice are overlooked Characteristics - bilirubin levels may ↑ with stress, strain, dehydration, fasting, infection or exposure to cold, in many individuals, jaundice is only evident when one of these triggers raises the bilirubin levels - presence of hyperbilirubinemia in the absence of hemolysis or structural liver damage - people with GS predominantly have elevated unconjugated bilirubin, while conjugated bilirubin is usually within the normal range and is less than 20% of the total - detect DNA mutations - polymerase chain reaction / DNA fragment sequ Crigler-Najjar syndrome: - Crigler-Najjar syndrome is a rare autosomal recessive (AR) disorders caused by absence (type I) or reduced activity (type II) of UDP-glucuronosyltransferase. Thisdisease disrupts the liver’s ability to conjugate bilirubin, resulting in severe unconjugated hyperbilirubinemia. - Is caused by a mutation in the UGT1A1 gene CN syndrome type I: Etiology: - Autosomal recessive inheritance: o UDP-glucuronosyltransferase activity is absent Clinical features: - Symptoms become apparent shortly after birth - Excessive, persistent neonatal jaundice - Neurological symptoms caused by kernicterus Diagnosis: - Very increased indirect bilirubin (20-50 mg/dL) - Normal liver function tests - No evidence of hemolysis Management: - Phototherapy - Plasmapheresis – during acute rises in serum - Liver transplantation – curative treatment Prognosis: - Incompatible with life because of Kernicterus  Kernicterus: An irreversible neurological syndrome that occurs in inadequately treated neonates with high levels of serum bilirubin (>25mg/dL) as a result of deposition of unconjugated bilirubin in the basal ganglia and/orbrain stem nuclei. Long-term sequelae include hearing impairment, movement disorders (athetosis), intellectual disability and dental enamel hypoplasia. CN syndrome type II: Etiology: - UDP-glucuronosyltransferase activity is markedly reduced Clinical features: - Often asymptomatic - No neonatal jaundice - No neurological symptoms Diagnosis: - Increased indirect bilirubin (< 20mg/dL) - Normal liver function tests - No evidence of hemolysis Treatment: - If patient become icteric: Phototherapy or Phenobarbital - Avoid hormonal contraception and hepatic enzyme inhibitors Prognosis: - Management of jaundice allows for normal quality of life Neonatal jaundice: Wilson disease Autosomal recessive disorder of copper homeostasis - affected gene is on chromosome 13 and encodes a highly conserved copper-transporting P-type adenosine triphosphatase (ATP7b) that excretes copper into bile Presents as hepatic or central nervous system involvement - liver disease occurs at an average age of 10 to 13 years in 45% of patients, rarely is seen before 3 years of age - 35% of patients present with neurologic signs (tremor, rigidity, dysarthria) a decade older than patients who have hepatic involvement - 10% present with psychiatric disturbances (depression, new-onset school problems, impulsive behavior) - 10% present with other manifestations, including hemolytic anemia, Fanconi syndrome (glycosuria, aminoaciduria), and cardiomyopathy - mixed conjugated and unconjugated hyperbilirubinemia - hepatic involvement ranges from asymptomatic transaminitis to acute liver failure with jaundice, cirrhosis, hepatic necrosis, and encephalopathy o Liver biopsy - nonspecific findings of steatosis and glycogen deposition, micronodular cirrhosis and piecemeal necrosis also can be seen Kaiser-Fleischer (KF) rings, representing copper deposition in Descemet’s membrane, are visible on a slitlamp examination of the eye Neurologic symptoms are attributed to copper deposition in the basal ganglia and include parkinsonian symptoms KF rings -present in patients who have neurologic symptoms, may be absent in patients who have liver disease Diagnosis clinical signs and symptoms slitlamp examination can be performed to evaluate for KF rings - laboratory findings of impaired hepatic copper metabolism: serum ceruloplasmin concentration ↓ - copper is not conjugated to the apoceruloplasmin synthesized by the hepatocyte - unconjugated apoceruloplasmin is degraded rapidly - urinary copper ↑ in a 24-hour collection  - liver biopsy - definitive genetic testing is now available for Wilson disease. Treatment is geared toward attaining and maintaining normal copper homeostasis - oral D- penicillamine, trientine- copper chelators - zinc acetate- prevents the absorption of copper from the gastrointestinal tract - to avoid copper-rich foods : shellfish, legumes, nuts, chocolate, and liver - liver transplantation is the treatment of choice for selected patients who have either advanced liver disease or fulminant liver failure Autoimmune hepatitis inflammatory hepatitis characterized by the development of pathologic autoantibodies to normal host proteins and a dense mononuclear infiltrate in the portal tracts in the absence of another cause AIH - two general categories classified by the type of autoantibodies produced: - anti-nuclear antibody/ anti-smooth muscle antibody (ANA/SMA) AIH - anti-liver kidney microsomal antibody 1 (LKM1) AIH Diagnosis suspected on the basis of clinical characteristics and demonstration of the autoantibodies, as well as an elevated immunoglobulin G value !!! Definitive diagnosis - liver biopsy- typical histologic picture - mononuclear infiltrate invading the hepatic parenchyma (periportal hepatitis), with periportal necrosis Therapy - In most cases- the disease responds well to immunosuppressive - Urgent liver transplantation - indicated if the patient presents in acute fulminant hepatic failure Neonatal hyperbilirubinemia Healthy term infants: the threshold typically is considered to be a level > 18 mg/ dL (> 308μmol/L) In such infants, risk increases with increasing hyperbilirubinemia, there is no level of hyperbilirubinemia that is considered safe Physiologic hyperbilirubinemia  occurs in almost all neonates  shorter neonatal RBC life span increases bilirubin production; deficient conjugation due to the deficiency of UGT decreases clearance; and low bacterial levels in the intestine combined with increased hydrolysis of conjugated bilirubin increase enterohepatic circulation  bilirubin levels can rise up to 18 mg/dL by 3 to 4 days of life (7 days in Asian infants) and fall thereafter Neurotoxicity  major consequence of neonatal hyperbilirubinemia  acute encephalopathy can be followed by a variety of neurologic impairments, including cerebral palsy and sensorimotor deficits; cognition is usuallyspared Kernicterus  the most severe form of neurotoxicity  can nearly always be prevented  kernicterus is brain damage caused by unconjugated bilirubin deposition in basal ganglia and brain stem nuclei, caused by either acute or chronic hyperbilirubinemia Normally, bilirubin bound to serum albumin stays in the intravascular space → bilirubin can cross the blood-brain barrier and cause kernicterus in certain situations: ▪ When serum bilirubin concentration is markedly elevated ▪ When serum albumin concentration is markedly low (eg, in preterm infants) ▪ When bilirubin is displaced from albumin by competitive binders Pathologic hyperbilirubinemia in term infants - Jaundice appears in the first 24 h, after the first week of life, or lasts > 2 wk - Total serum bilirubin (TSB) rises by > 5 mg/ dL/ day - TSB is > 18 mg/ dL - Infant shows symptoms or signs of a serious illness Some of the most common pathologic causes are: ▪ Immune and nonimmune hemolytic anemia ▪ G6PD deficiency ▪ Hematoma resorption ▪ Sepsis ▪ Hypothyroidism Infants who are premature, small for gestational age, and/or ill (eg, with sepsis, hypotermia, or hypoxia) ->much greater risk Definitive treatment of hyperbilirubinemia involves: Phototherapy, Exchange transfusion 1c. Side-effects of long-term treatment with corticosteroids andprevention possibilities Glucocorticoids Mineralocorticoids  Short acting (36h): dexamethasone Corticosteroid toxicity depends on the dose that is administered over a certain period of time. Therefore, even low doses can have toxic effects if administered long-term. If glucocorticoids are administered once or only briefly (e.g. for treatment of anaphylaxis),there are usually no significant side effects even in high doses. Routes of administration can be: - Topical (e.g. eye, skin, mucous membranes) - Local injection (e.g. intraarticular) - Inhaled - Oral - Parenteral Effects of corticosteroids: - Anti-inflammatory and immunosuppressive: o Acute effects (within minutes) ▪ Decreased vasodilation and decreased capillary permeability ▪ Decreased leukocyte migration to inflammatory foci  o Long-term effects (within hours) ▪ Neutrophilic leukocytosis ▪ Decreased AA derivatives (by inhibiting phospholipase A2) ▪ Down expression of pro-inflammatory genes ▪ Increase expression of anti-inflammatory genes - Mineralocorticoid properties – only in high doses and over long periods of time: o Reduce sodium excretion – SE: Hypernatremia o Increase potassium excretion – SE: Hypokalemia - Anti-proliferative: o Trigger cell apoptosis and inhibit fibroblast proliferation Corticosteroids – side-effects: - Skin: o Skin atrophy – due to loss of dermal collagen o Stretch marks, purpura (purple striae), acne, hypertrichosis - CVS: o Hypertension - Metabolism: o Weight gain/redistribution of fat: ▪ Truncal obesity, buffalo hump, facie lunata (“Cushingoid appearance”) o Hyperglycemia -> glucocorticoid-induced diabetes o Proteolysis – contributes to hyperglycemia o Lipolysis – contributes to hyperlipidemia causing redistribution of fat o Hypocalcemia leading to PTH activation thereby secondary osteoporosis ▪ Glucocorticoids affect calcium handling by increasing renal excretionand inhibiting gastrointestinal absorption - CNS: o Mood disorders, cognitive disorders (e.g. memory deficits), psychosis (inhigh doses over longer periods of time) - Eyes: o Cataract, Glaucoma - Other: o Adrenocortical atrophy ▪ Acute adrenal insufficiency – if sudden discontinuation o Avascular necrosis of bone o Osteoporosis, osteopenia: ▪ Decreased bone formation and increased bone resorption ▪ Growth inhibition of children o Myopathy – progressive weakness of proximal limb muscles, myalgia o Peptic ulcers and GI hemorrhage o Immunosuppression Prevention possibilities: - Tapering to avoid toxicity in long-term administration (> 3 weeks) - Gastric ulcers: o PPI - Osteoporosis: o Vit D, Calcium - Etc. 2a. Pneumonia in older children Pneumonia: Definition: - “Pneumonia is an infection of the lower respiratory tract that involves the airways and parenchyma with consolidation of the alveolar spaces” - Lower RTI is often used to encompass bronchitis, bronchiolitis, pneumonia, or any combination of the three. - Lobar pneumonia describes pneumonia localized to one or more lobes of the lung - Atypical pneumonia describes patterns typically more diffuse or interstitial than lobar pneumonia, and presents with a clinical pattern which is different from the normal features of pneumonia. - Interstitial pneumonitis refers to inflammation of the interstitium, which is composed of walls of the alveoli, the alveolar sacs and ducts, and the bronchioles.It is characteristic of acute viral infections but may also be chronic inflammation. - Bronchopneumonia refers to inflammation of the lung that is centered in the bronchioles and leads to production of a mucopurulent exudate that obstruct some of these small airways and causes patchy consolidation of the adjacent lobules Epidemiology: - Pneumonia kills more children under the age of five than any other illness in everyregion of the world - It is estimated that of the 9 million child deaths in 2007, 20% were due to pneumonia - Immunization have had a great impact on the incidence of pneumonia caused by Pertussis, Diphtheria, Measles, Haemophilus, Influenza and S. pneumoniae - Risk factors for lower RTI include: o GERD, neurological impairment (aspiration), immunocompromising situations, anatomic abnormalities of respiratory tract, stay in hospital (ICU). Etiology: - Community-acquired pneumonia o Older children: ▪ Bacterial – more common in older children. Mycoplasma pneumoniae, S. pneumoniae, C. pneumoniae ▪ Viral: Influenza, Adenovirus, Parainfluenza  o Pneumonia in immunocompromised patients: ▪ Mycobacterium avium complex ▪ Aspergillus ▪ CMV ▪ Pneumocystis jiroveci o Patients with cystic fibrosis: ▪ S. aureus (in infancy) ▪ P. aeruginosa, B. cepacia (older patients) Clinical features: - Constitutional symptoms (e.g. fever, chills, malaise, fatigue) - Productive cough – with purulent sputum (yellow-greenish) - bacterial - Tachypnea, dyspnea – tachypnea is the most sensitive and specific sign ofpneumonia! Age: RR: Indication of severe infection: > 5 years >20 >50 - Chest indrawing, other signs of increased work of breathing - Crackles, bronchial and decreased breath sounds on auscultation - Dullness on percussion Diagnosis: - Pneumonia history: o Presence of cough, difficulty breathing, shortness of breath, chest pain, fever, recent upper respiratory tract infections o Associated symptoms (e.g. headache, lethargy, pharyngitis, nausea,vomiting diarrhea, abdominal pain, rash) o Duration of symptoms o Immunization status, TB exposure, maternal chlamydia/GBS status inpregnancy, choking episodes, previous episodes, previous antibiotics o Contacts, travel history, day care attendance, animal exposure - Vital signs that should be taken include: o RR, HR, Temperature, O2 sat. ▪ Any child with an increased RR should be immediately identified ashaving possible pneumonia. - Dehydration status: o Sign of severe infection that may require hospitalization: ▪ Fluid and nutrition intake, urine output evaluation - Routine blood work – not indicated in uncomplicated infections o Consider the following: ▪ CBC, particularly WBC and CRP ▪ Electrolytes, particularly sodium ▪ Consider blood cultures, sputum cultures ▪ TB testing if needed - CXR (not indicated in children with mild, uncomplicated infections who will be treated as outpatients): o Consider if infection is severe, diagnosis otherwise inconclusive, to exclude other causes of dyspnea (e.g. foreign body, heart failure), to look for compli-cations or to exclude pneumonia in an infant less than 3 months with fever Treatment: - Supportive measures: o Oxygen therapy o Anti-pyretic – paracetamol o Bronchodilators o Suction of secretions – if necessary o Fluid maintenance – avoid overhydration ▪ Encourage oral fluids and food as soon as can be taken - Monitoring should include: o RR, work of breathing, auscultation o Temperature o HR o O2 sat - Criteria for intensive care: o O2 sat < 92 in FiO2 of > 0.6 o Shock o Rising respiratory rate and rising pulse rate with clinical evidence of severe respiratory distress and exhaustion, with or without a raised PaCO2 ▪ Respiratory failure: Low PO2 (type 1), Low PO2 + High PCO2 (type 2) o Recurrent apnea or slow irregular breathing - Antibiotics – dose according to child’s weight! o Antibiotics that are used depend on age of patient and etiology: ▪ Common antibiotics for treating pneumonia:  Oral antibiotics: o Penicillin – Amoxicillin, Amoxicilin-Clavulanate o Macrolides – Azithromycin, Clarithromycin o Cephalosporins – 2nd generation: Cefaclor  IV antibiotics o Penicillin: Amoxicillin, Ampicillin, Benzyl Penicillin o Cephalosporins: ▪ Cefuroxime (2nd generation) ▪ Cefotaxime (3rd generation) o Amoxicillin is DOC for outpatients o IV 3rd generation cephalosporins for inpatients ▪ In child less than 1 year o IV ampicillin or penicillin for inpatients ▪ In child over 1 year of age o Atypical pneumonia (most common in older children > 5 years) ▪ Macrolides Prevention: - Vaccination – measles, Pneumococcus, HiB 2b. Differential diagnosis of Conjugated hyperbilirubinemia INTRO Q. 1b Conjugated hyperbilirubinemia: - A conjugated (‘direct’) bilirubin concentration > 2mg/dL if the total bilirubin is < 5mg/dL, or more than 20% of the total bilirubin if the bilirubin is > 5 mg/dL. Due to intrahepatic  cholestasis (hepatocellular injury through infection, cirrhosis, inflammation, etc.) or extrahepatic outflow obstruction (biliary obstruction by calculi,malignancies, strictures etc.) - It is never physiological Conjugated hyperbilirubinemia: - Decreased bilirubin excretion: o Intrahepatic cholestasis: ▪ Sepsis, hepatitis, TORCH, cystic fibrosis o Extrahepatic cholestasis: ▪ Billiary atresia, choledochal cyst, tumors/strictures - Intrahepatic pathologies: o Infectious hepatitis o Metabolic diseases: ▪ Dublin-Johnson, Rotor syndrome, Alpha-1-AT deficiency o Idiopathic neonatal hepatitis o Alagille syndrome Dublin-Johnson syndrome: - An autosomal recessive disorder causing inherited hyperbilirubinemia due to defective MRP2 transporter. The defective transporter impairs movement of conjugated bilirubin from the hepatocyte to the bile canaliculi. - Clinical features include mild to moderate jaundice during adolescence that worsens because of medication (particularly contraceptives) or pregnancy. - Diagnosed based on findings of direct hyperbilirubinemia as well as liver biopsy showing darker granular pigmentation. - No treatment required. Rotor syndrome: - An autosomal recessive disorder causing inherited hyperbilirubinemia due to impaired transport and reduce storage capacity of conjugated bilirubin. It is usually asymptomatic. - The diagnosis is based on direct hyperbilirubinemia and mild, indirect hyperbilirubinemia, normal liver function tests and increased urinary coproporphyrins I and III. - No treatment required. Congenital TORCH infections – vertically transmitted infections that are capable ofsignifi cantly influencing fetal and neonatal morbidity and mortality Biliary atresia: Definition: - Obliteration or discontinuity of the extrahepatic biliary system, most commonly of the common bile duct Pathophysiology: - Obstruction of bile flow leads to cholestasis, which leads to secondary biliary cirrhosis and portal hypertension Clinical features: - Prolonged neonatal jaundice - Acholic stools, dark urine - Hepatomegaly Diagnosis: - Conjugated hyperbilirubinemia - Mild/moderate increase in aminotransferases and ALP, increased GTP - USG: o Absence of gallbladder, no dilatation of the biliary tree - Intraoperative cholangiography Treatment: - Hepatoportoenterostomy - In cases of liver cirrhosis -> Liver transplantation (primary reason for liver transplantation in children) 2c. Cutaneous infections in children Superficial bacterial infections: Impetigo Definition: - Impetigo is an infectious, predominantly pediatric skin disease caused by S. aureus or, less commonly, S. pyogenes. There are both bullous and non-bullous variants. Epidemiology: - Most common bacterial skin infection among children - Age: 2-6 years of age – most commonly - Highly contagious o Route of infection: ▪ Primary – bacterial infection to previously healthy skin ▪ Secondary (Impetiginisation) – secondary infection of pre-existing skinlesion (e.g. scabies, insect bites, eczema) Etiology: - S. aureus – 80% of causes o Causes bullous and non-bullous impetigo – S. aureus produce exfoliativetoxins A and B which are responsible for bullous impetigo - S. pyogenes o Causes non-bullous impetigo only - Predisposing factors: o Warm and humid climate o Unsanitary living conditions; poor personal hygiene o Underlying atopic dermatitis, diabetes mellitus or immunodeficiency Clinical features: - Non-bullous impetigo – 70% of cases o Lesions: Papules -> Small vesicles surrounded by erythema -> Pustules thatrupture -> Oozing secretion that dries -> Honey-colored crusts -> Heal without scarring o Localization: Face, especially around nose and mouth (most common),extremities o Pruritus may be present, regional lymphadenopathy - Bullous impetigo – 30% of cases o Lesions: Vesicles that grow to form large, fl accid bullae, which go on torupture and form thin, brown crusts ▪ Lateral traction causes sloughing of the skin (positive Nikolsky sign) o Localization: trunk and upper extremities - Ecthyma: o Ulcerative impetigo that extends into the dermis (coin-sized, superficial ulcer,with a ‘punched-out’ appearance) Note: Impetigo should be suspected in children presenting with honey-colored crusts around the mouth and nose. Diagnosis: - Based on clinical presentation - Culture – in cases with inconclusive diagnosis Treatment: - Wound cleansing with antibacterial washes (e.g. chlorhexidine) - Non-bullous impetigo with single lesions or small areas: o Topical antibiotics - Bullous impetigo, ecthyma, or severe non-bullous impetigo (widespread): o 1st generation cephalosporins (e.g. cephalexin) or dicloxacillin o Alternative: Amoxicillin-clavulanate, macrolides o If MRSA – clindamycin, TMP-SMX Complications: - If GAS infection: o Acute PSGN - Superinfection Erysipelas Definition: - Erysipelas is a superficial skin infection involving the upper dermis, with lymphangitis and lymphadenitis. Etiology: - Group A Streptococcus – S. pyogenes o Entry via minor skin injury -> Infection of upper dermis + spread viasuperficial lymphatic vessels - Other beta-hemolytic streptococci Clinical features: - Location: o Lower limb – 80% of cases o Face - Sudden onset, tender, sharply demarcated skin lesion, with erythema, edema and warmth - Lymphangitis – red streak radiating from the skin lesions - Systemic symptoms – fever, chills, nausea, headaches, myalgia/arthralgia Diagnosis: - Clinical diagnosis - Laboratory show increased CRP, ESR and leukocytosisTreatment: - Antibiotics (e.g. penicillin V, cephalexin or dicloxacillin) - If severe – surgical debridement and other antibiotics Cellulitis: - Rapidly spreading local infection of the deep dermis and subcutaneous tissues - Caused by S. aureus (purulent cellulitis), S. pyogenes (nonpurulent cellulitis) or P.multocida (cat/dog bites) - Presents with erythematous skin lesion with poorly defined margins and possibly systemic symptoms – may also present as orbital or periorbital (preseptal) cellulitis. Superficial viral infections: - Molluscum contagiosum o A self-limiting skin infection caused by molluscum contagiosum virus – typically presents with multiple, benign, non-tender, skin-colored, pearly,dome-shaped papules with central umbilication. o Common in young children and adolescents – present on face, trunk or extremities o Treated by cryotherapy or curettage, if there is no spontaneous remission. - Human papilloma virus (Warts) o Hyperkeratotic lesions caused by HPV through direct skin contact. Appear ascauliflower-like lesions, commonly found on fingers, palms, or soles of feet. - Herpes simplex o HSV-1: Labial herpes (mostly) o HSV-2: Genital herpes (mostly) 3a. Tuberculosis Tuberculosis: Definition: - Tuberculosis is a chronic bacterial infection that spread via inhalation and typicallyaffects the lungs. Epidemiology: - Slowly declining incidence of TB infections in Europe o Highest prevalence in Romania - More lethal than any other contagious disease Classification: - Pulmonary TB – which can be distinguished as: o Primary disease o Secondary disease - Extrapulmonary TB o Can affect almost every organ (e.g. lymph nodes, pleura, upper airways, skeletal, genitourinary, pericardial, CNS, GI etc.) Etiology: - Mycobacterium tuberculosis complex (TBC) – including M. tuberculosis, M.africanum, M. canettii etc. o Vaccine strain (BCG) – M. bovis - Risk factors: - Immunosuppression - Drug abuse, alcoholism - Malnutrition - Diabetes mellitus - Pre-existing lung disease - Poverty - Residents and employees of prisons, homeless shelters etc. - Treatment with TNF-a inhibitors – reactivation of TB Pathogenesis: - In case of an infection, the vast majority of patient does not result in clinical apparent infection. However, 10-30% develop Primary infection: o Primary tuberculosis (Primary infection) occurs when the organism settles in the lung causing inflammatory reaction (Gohn focus) – here the bacilli multiplies and spread via lymphatics causing lymphadenopathy (Gohn complex – lung lesion, lymphadenopathy and lymphangitis) – the primary infection can develop into: ▪ Latent tuberculosis (90% of cases)  Definition: Primary infection without any pathological findings on radiological imaging, but with positive tuberculin test.However, it is non-transmissible.  Bacilli remains dormant in granulomas and can develop/reactivate to post-primary infection (Secondary disease) ▪ Primary progressive tuberculosis (1-5% of cases):  Definition: Primary infection with radiological-pathological findings of tuberculosis. Occurs when the cell mediatedimmunity fails/weak  At risk patients are immunocompromised patients and childrenunder the age of 4 years – clinical picture depends on the age and dissemination (may be pulmonary, extrapulmonary or disseminated disease) o Reactivation tuberculosis (Secondary disease): ▪ Definition: Following a latent primary TB infection. 80% of secondaryinfections begin in the lungs (upper lobes are mainly affected) ▪ Occurs when the organism has been dormant, and something triggersit to reactive and proliferates Note: M. tuberculosis remains dormant within the host and may be reactivated once the immune system becomes compromised (e.g. byhigh doses of glucocorticoids or chemotherapeutic agents, HIV infection) Note: Primary infection is most common in young children, while post-primary (secondary infection) is most common in adolescences.  Clinical features - Latent infection: o Asymptomatic and patient is not contagious - Active infection (either primary or reactivated): o Complaints – non-specific! ▪ Headache, weakness, poor appetite, weight loss, sweating o Signs and symptoms – non-specific! ▪ Coughing ▪ Fever, subfebrility ▪ Haemoptoe ▪ Vomiting, nausea The most common clinical presentation in children with TB is – in this case wehave to consider TB: o Prolonged fever o Failure to thrive o Unresolved pneumonia o Persistent lymphadenopathy - Extrapulmonary forms of TB: o Most common sites include: ▪ Bones (e.g. Pott’s disease – TB spondylitis) ▪ Pleura (e.g. pleuritis) ▪ Lymphatics ▪ Liver o Other places include: ▪ CNS (e.g. meningitis) ▪ Urogenital (e.g. prostatitis, nephritis, salpingitis etc.) ▪ Gastrointestinal ▪ Skin (e.g. lupus vulgaris – reddish-brown nodules becoming ulcers) ▪ Heart (e.g. pericarditis – risk of constrictive pericarditis) ▪ Adrenals Note: Childhood TB disease most commonly presents as pulmonary (77%) or lymphatic (13%). In infancy pulmonary TB and CNS are mostcommon. - Miliary tuberculosis: o Definition: ▪ Massive lymphohematogenous spread of M.tuberculosis from a pulmonary or extrapulmonary focus with multiple organ involvement and very small granuloma lesions  Accounts for about 20% of all extrapulmonary TB cases  May present 2-5 months after initial infection or years after o Clinical features: ▪ Pulmonary involvement (most common) ▪ CXR – multiple, small, nodular densities of equal size scatteredthroughout the lungs – “millet seed” appearance ▪ Other commonly affected organs  CNS, Choroid, Skin, Liver/spleen, Kidneys, Adrenal glands Diagnosis: - History: o Assess risk of active TB through history and physical examination. - Clinical picture o A child with prolonged fever, unresolved pneumonia, failure to thrive and lymphadenopathy – always consider TB - Radioimaging: o CXR – hilar lymphadenopathy, Gohn complex, upper cavitary lung lesions o CT/MRI - Bronchological examination:  o Bronchoscopy, fibroscopy o Bronchoalveolar lavage - Microbiology: o Collect specimen from sputum, gastric washing, laryngeal swab, bronchoscopy, biopsy etc. o Sputum microscopy: ▪ With acid-fast stain (Ziehl-Neelsen stain) – old way ▪ Fluorescence microscopy: auramine-rhodamine staining – new way o Culture (gold standard): ▪ Used for species identification, sensitivity testing, and to identifypossible resistances. May take up to six weeks. ▪ BACTEC ▪ PCR testing - Immunological testing: o Tuberculin skin test – Mantoux test, Heaf test ▪ Measure the skin lesion after injection of purified protein derivative intradermally into ventral forearm. The tuberculin causes a delayed HSR mediated by T cells  > 15mm – positive if low risk factors (hyperreaction) ▪ False positive in cases of BCG vaccination or infection by non-TB mycobacterium ▪ False negative in cases of immunosuppression o IGRA (Interferon gamma release assay): ▪ ELISA test that measures the level of IFN-y expressed by T-cells aftercoming into contact with synthetic TB peptides ▪ No false positives o NAAT (Nucleic acid amplification test) o Xpert MTB/RIF: ▪ Newest option – simultaneous TB diagnosis and ATB sensitivity test inless than 2 hours Interpretation of the PPD test: Diameter of induration: Consider positive in following groups: > 5mm Immunosuppressed patients/HIV patients > 10mm Patients with high risk of reactivation > 15mm, highly positive Always consider positive, even without risk factors Differential diagnosis: - Granulomatous diseases - Nontuberculous mycobacterial infections and MAC infection - Atypical pneumonia - Lung cancer Treatment: - Principles in treatment (same as in adults): o If active disease: ▪ Minimum 6 months combined drug-therapy with intensive phase (2months; 3-4 drugs) and continuation phase (4-7 months; 2 drugs) ▪ Longer periods of treatment in extrapulmonary TB ▪ Administration under surveillance – Directly observed therapy (DOT) ▪ Isolation until secretions are negative o Latent TB: ▪ Isoniazid for 6 months OR Isoniazid + Rifampicin for 3 months - Drugs used in tuberculosis (anti-TB drugs): RIPE o Rifampin o Isoniazid o Pyranzinamine o Ethambutol - Multidrug resistant TB o Delamanid (for children)  - Monitor drug side-effects: o Renal retention parameters, ophthalmology, ENT, liver function tests - Side-effects of drugs: o Isoniazid – Hepatotoxicity, Peripheral polyneuropathy, Optic neuritis o Rifampin – Hepatotoxicity, CYP-inducer, Red/orange body fluids (urine,tears) o Pyrazinamide – Hepatotoxicity, Hyperuricemia, Arthralgia, Myopathy o Ethambutol – Optic neuritis Prevention: - BCG vaccination - Notification - Post-exposure management Congenital tuberculosis – very rare: - Vertical transmission to fetus from the mother (e.g. hematogenous, in-uteroaspiration or infection by infectious secretions) - Clinical picture may be non-specific – importance of clinical suspicion and imaging(milliary TB). o TB in fetus may presents with low birth weight, IUGR or preterm births o Most common features of congenital TB include: ▪ Poor feeding, fever, irritability, FTT, cough ▪ Possible hepatosplenomegaly, lymphadenopathy ▪ Risk of meningitis, septicemia 3b. Differential diagnosis of Nausea and Vomiting in children Introduction: Nausea and vomiting are common sequelae of a multitude of disorders that can range from mild, self-limited illnesses to severe, life-threatening conditions. The symptoms of nausea and vomiting may be caused by many pathologic states involving several systems(including gastrointestinal, neurological, renal, and psychiatric). Younger children may notbe able to describe nausea, which may further complicate the diagnosis. The best course of action should be dictated by the medical history, taking into consideration clinical features of specific disorders and their relative frequency among children in different agegroups. The most important consideration during the initial encounter is recognition of serious conditions, such as intestinal obstruction and increased ICP, for which immediateintervention is required. Definition: Vomiting (emesis) refers to the forceful oral expulsion of gastric contentsassociated with contraction of the abdominal and chest wall musculature. o Vomitus often has a slightly yellow tinge, which is caused by reflux of smallamounts of bile into the stomach o If green or bright yellow color, the vomitus is considered bilious, indicatinglarger amounts of bile in the stomach – bilious vomiting is associated withintestinal obstruction Nausea generally refers to an unmistakable sensation of unpleasantness that may precede vomiting, but may be present even in a child who does not vomit. It is often associated with autonomic changes such as salivation, increased heart rates, and a reduction in gastric tone and mucosal blood fl ow. Differential diagnosis of Nausea and Vomiting in children: - Concerning signs that may indicate serious cause of nausea and vomiting: - Nonspecific symptoms: - Prolonged vomiting - Profound lethargy - Significant weight loss - Symptoms of GI obstruction or disease: - Bilious vomiting - Projectile vomiting in an infant three to six weeks of age - Hematemesis - Hematochezia (rectal bleeding) - Marked abdominal distension and tenderness  - Symptoms or signs suggesting neurologic disease: - Bulging fontanelle in neonate/young infant - Headache, positional triggers for vomiting or vomiting on awakening,and/or vomiting with lack of nausea - Altered consciousness, seizures, or focal neurological abnormalities - History of head trauma - Hypotension and/or hyponatremia and hyperkalemia - According to age group: Neonates and young infants: - GERD - Enteropathy - Pyloric stenosis - Adrenal insufficiency - Intestinal obstruction; Malrotation with volvulus, Hirschsprung disease - Inborn error of metabolism Older infants and children: - Gastroenteritis, other infections - Gastroparesis - Intussusception - Anaphylaxis - Adrenal crisis - Intracranial hypertension - Migraine - Medical child abuse Adolescents - Dyspepsia - Appendicitis - Inflammatory bowel disease - Pregnancy - Bulimia, psychogenic vomiting Differential diagnosis: Etiology Iatrogenic and toxic causes: - Medication (e.g. chemotherapy, antiarrhythmic, antibiotics, antiepileptic) - Alcohol, illegal drugs, other toxins Infectious causes: - Viral gastroenteritis – most common! - Bacterial gastroenteritis Gastrointestinal causes: - Functional dyspepsia - Irritable bowel syndrome, Inflammatory bowel disease - Appendicitis, Cholecystitis, Pancreatitis, Hepatitis - Intestinal obstruction; volvulus, dysmotility, intussusception, pyloric stenosis - Gastroparesis, gastric ulcer - GERD CNS and psychiatric causes: - Intracranial hypertension – infarction, infection, malignancy, head injury - This might give vomiting without nausea - Affection of vestibulocochlear nerve and balance - Migraine - Emotional and physical stress - Anorexia nervosa, bulimia nervosa, anxiety Other: - Pregnancy - Metabolic abnormalities – acidosis, uremia, adrenal dysfunction Approach to management: - The exclusion of life-threatening disorders such as bowel obstruction, diabetic ketoacidosis,  adrenal crisis, toxic ingestion or intracranial hypertension is very important. In both urgent care and routine outpatient settings, the followings threesteps should generally be undertaken in patients with nausea and vomiting: 1) The etiology should be sought, taking into account the child’s age, and whether the nausea and vomiting is acute, chronic, or episodic. 2) The consequences or complications of nausea and vomiting (e.g. fluid deprivation, hypokalemia, and metabolic alkalosis) should be identified and corrected. 3) Targeted therapy should be provided, when possible (e.g. surgery for bowel obstruction or dietary changes for food sensitivity). Evaluation: - Important points that should be taken into account: o Presence of abdominal pain, headache or other alarming signs (e.g. ICHTN) o Differentiate between vomiting and regurgitation, associated nausea o When the symptoms started? ▪ Acute (e.g. cholecystitis, food poisoning, gastroenteritis, drugs, etc.) ▪ Chronic (e.g. GERD, gastroparesis, medication, metabolic,pregnancy) o How long did it last? ▪ Hours, days (e.g. food poisoning, viral gastroenteritis, cholecystitis) ▪ Weeks, months (e.g. obstruction, CNS) o Associated pain? ▪ If pain resolves after vomiting – think obstruction ▪ Localization, intensity and timing  Upper, right quadrant – biliary disorders  Epigastric – gastric ulcer, pancreatitis  Lower, right quadrant – appendicitis  Lower abdominal area – genitourinary o Relation to meals? ▪ Before breakfast – increased ICP, uremia, pregnancy ▪ At or after meals – functional dyspepsia, pyloric stenosis ▪ Hours after meals – obstruction, gastroparesis ▪ Persistent, with no relation to meals o How does the vomitus look like? ▪ Indigested food – esophageal dysmotility disorders ▪ Partly digested – obstruction in antrum, gastroparesis ▪ Biliary – proximal obstruction ▪ Feculent – fistula o Toxin exposure? ▪ Food intake, other people sick, viral symptoms ▪ Chemotherapy, radiation therapy ▪ Medication/drugs 3c. Prematurity and Low birth weight complications and consequences Definition: Prematurity - Preterm birth is defined as live birth between 20 0/7 weeks and 36 6/7 weeks of gestation. It is subcategorized by WHO into: o Moderate to late preterm 32 to < 37 weeks o Very preterm 28 to 40 years ▪ BMI of mother < 19 or > 35 ▪ Smoking, poor nutritional status ▪ Psychosocial stress ▪ Chronic disease (e.g. diabetes, thyroid disease) ▪ Intrauterine infection, Urinary tract infection, STI ▪ Severe bacterial vaginosis ▪ Polyhydramnion, Preeclampsia, Placentia previa, Abruptio placentae ▪ PROM Problems related to prematurity: - Skin: o Loss of heat and fluids because of thin epidermis, low subcutaneous fatand big surface area compared to weight – risk of hypothermia and dehydration - Pulmonary: o Soft and indulging chest, weak musculature, low surfactant, less developedCNS reflex mechanisms - Liver: o Immaturity of liver enzymes (e.g. conjugation of bilirubin) - Kidney: o Low concentration ability resulting in fluid, electrolyte and acid-basebalance disorders. - GIT: o Low levels of hormones and enzymes related to digestion o Small vitamin stores o Immature glycolysis - CNS: o Immature reflexes resulting in apnea, bradycardia and circulatory disturbances - Immunity: o Increased tendency to infection due to immature immune system o Increased tendency of sepsis Note: Special focus on decreased temperature, hypoglycemia and respiratory problems in premature neonates. Clinical manifestation  Small body and disproportional large head  Less rounded features due to lack of fat stores  Fine hair (lanugo) covering much of the body  Low body temp  Respiratory distress due to lack of surfactant  Lack of sucking and swallowing reflexes -> feeding problems Treatment: - Medication: o Corticosteroids: ▪ Used in ventilatory-dependent preterms to prevent bronchopulmonary dysplasia. This allow for an increase in lung function and less cases of chronic lung disease. - Oxygen therapy  - Phototherapy for hyperbilirubinemia - Continuous naso/orogastic nutrition - Temperature regulation Complications: General complications: o Respiratory disturbances – Respiratory distress syndrome o Temperature disturbances o Decreased growth and development o Psychosocial complications: ▪ difficulties in language, concentration/attention, learning, socialinteractions, motor development and mental health Specific, serious complications: MUST KNOW ALL THESE. o Peri/intraventricular hemorrhage o Cystic periventricular leukomalacia o Retinopathy of prematurity o Hearing impairment o Bronchopulmonary dysplasia (old and new) o Persistent ductus arteriosus o Necrotizing enterocolitis o Neonatal hypocalcemia Complications of the prematurity Peri- Intra- Ventricular Hemorrhage (PIVH) Intraventricular hemorrhage (IVH) of the newborn is bleeding into the fluid-filled areas (ventricles) inside the brain. The condition occurs most often in babies that are born early (premature). With BW less then 1500g (20%), under 34 GA Infants born more than 10 weeks early are at highest risk for this type of bleeding. The smaller and more premature an infant is, the higher the risk for IVH. This is because blood vessels in the brain of premature infants are not yet fully developed. They are very fragile as a result. The blood vessels grow stronger in the last 10 weeks of pregnancy. PIVH Changes of the cerebral perfusion pressure: Vaginal delivery, If ventilation support was needed, PTX, asfyxia, apnoe, hyperkapnia, hypokapnia cardiopathies, PDA infections, sepsis shock, or if we give too much or more fluid boluses PIVH Clinically – sometimes asymptomatic, sometimes deterioration, seizures, coma, feeding intolerance, increased ventilation support needed, anemia. Usually unilateral PIVH Classification: There are four types of IVH. These are called "grades" and are based on the degree of bleeding. ▪ Grades 1 and 2 involve a smaller amount of bleeding. Most of the time, there are no long-term problems as a result of the bleeding. Grade 1 is also referred to as germinal matrix hemorrhage (GMH). ▪ Grades 3 and 4 involve more severe bleeding. The blood presses on (grade 3) or directly involves (grade 4) brain tissue. Grade 4 is also called an intraparenchymal hemorrhage. Blood clots can form and block the flow of cerebrospinal fluid. This can lead to increased fluid in the brain (hydrocephalus). Prevention Antenatally- centralisation of the hig risk pregnancies Postnatally- do not give fluid boluses, use the optimal and effective treatment strategy, less invasive but if ventilation support is necessary then it must be set to the optimal way Treatment and decreasing of the cerebral pulsy Keep the cerebral perfusion pressure in the zone of autoregulation Use the sofisticated ventilation modes or non invasive ventilation Treat and prevent the apnoe Cord milking ?  Follow closelly the PDA haemodynamic interactions Cystic periventricular leukomalacia (cPVL) Is a form of white-matter brain injury, characterized by the necrosis (more often coagulation) of white matter near the lateral ventricles. It can affect newborns and (less commonly) fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. We saw it in 5- 15% of premature newborns, with GA less then 32 week, BW less then 1500 g in white matter around the side ventricles. Etiopathogenesis: In the process of morphogenesis focuses PVL pass through three stages: 1) necrosis, 2) resorption, 3) the formation gliosis scars or cysts. a. Cysts occur when large and confluent focuses of PVL, with mixed necrosis (kollikvacia in the center and coagulation rim at the periphery). Around the foci is generally defined area of other lesions of the brain white matter - the death of prooligodendrocytes, proliferation microgliocytes and astrocytes, swelling, bleeding, loss of capillaries, and others (the so-called "diffuse component PVL"). However, diffuse lesions without necrosis are not PVL. Increased risk in premature rupture of membranes, chorioamnoinitis, twin to twin transfusion syndrome, pathology of the umbilical cord, oligohydramnion USG is the tool for verification or MRI - only in severe or diffuse cases Age at diagnosis is inversely related to gestational age and degree of prematurity: Gestational age* Age at onset < 30 weeks 20.2 days 31-33 weeks 13.8 days > 34 weeks 5.4 days Full term 1-3 days Treatment and decreasing of the cerebral pulsy Keep the cerebral perfusion pressure in the zone of autoregulation Use the sofisticated ventilation modes or non invasive ventilation Treat and prevent the apnoe Cord milking ? Follow closelly the PDA haemodynamic interactions ROP- retinopathy of prematurity In 1940 first written as rentrolentálna fibrodysplázia Prematurity, Immaturity Oxygen toxicity – hypoxia, hyperoxia Blood transfusions increasing the risk Prevention Limits are crutial 90 – 95 ( optimal ) Screening- in all babies delivered before 32 week, and in all under 1500 g (a) Retina vessels in the process of their formation and progressive covering of the retina surface. (b) Hyperoxia at this formative stage suppresses VEGF and, consequently, results in regression of newly formed vessels. (c) Upon return to normal air, the ischemic retina upregulates VEGF to high levels, causing excessive formation of leaky vessels. To antagonize VEGF at this stage has been suggested as a strategy to reduce adverse vessel formation. (d) An alternative strategy proposed by Shih et al. (2) is to protect retina vessels from oxygen-induced obliteration through administration of PlGF-1 Therapy Early diagnosis Laser coagulation or cryotherapy, Or intravitral application of anti- VGF - Avastin (Bavacizumab) The aim is influance the neovascularisation. Consequences: blindness, anatomic a function changes of the retina, secondary glaucoma, myopia, amblyopia, strabismus Bronchopulmonary dysplasia (BPD) Is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are present tend to not be mature enough to function normal.It is more common in infants with low birth weight (LBW) and those who receive prolonged mechanical ventilation to treat respiratory distress syndrome (RDS). It results in significant morbidity and mortality. The definition of BPD has continued to evolve primarily due to changes in the population, such as more survivors at earlier gestational ages, and improved neonatal management including surfactant, antenatal glucocorticoid therapy, and less aggressive mechanical ventilation. Classification: Classic BPD: New BPD: Less fibrosis Extensive fibroproliferation Less regional heterogenicity Atelectasis and or hyperinflation Milder airway disease Airway epithelial and smooth muscle lesions Redused alveolarisation Decreased alveoli and abnormal vessels Dysmorphic vascular growt Risk factors Not well controlled ventilatory support Fluctuation of the FiO2 Early pneumopathies (hyaline mebrane disease or MAS) Infetions (chorioamnitis, sepsis) Extreme prematurity- anatomical and functional immaturity of the lungs Postanatal damage of the lungs PIE (pulmonary interstital emphysema)  High inspiratory pressures used for a long time Atelectasis Increased resistance of the airway Increased intrapulmonary pressure Boys are more sensitive Prevention Prenatal care Timing of the delivery Optimal lung recruitment The best possible support of the ventilation in time (CPAP, SiPAP, Volume AC) Oxygen saturation limits StcO2 90 - 95 Ductus arteriosus persistent (DAP) Fetal circulation Systemic resistance Pulmonary resistance Postnatally left to right flow Closing – (decreased)PGE2, (increased) O2, corticoids Opening – (increased) PGE2 (decreased) O2, NO Closing alone: 24 hrs - 50% 48 hrs - 90% 72 hrs - 99.9% In premature babies it is individual Why it is importatnt to follow the PDA patency? It will tell us about the transition Sign of the PVR PDA increasing the risk for PIVH and NEC For the selection of the ventilation support strategy CPAP verzus UPV – Volume / AC Use or not use - Surfactant Monitoring the flow in PPHN We evaluating the circulation When the treatment is not necessary Good prenatal care, optimal timing of the delivery Spontaneus closure Not increased risk for PIVH, NEC, BPD CPAP is enough for the ventilation When treat and follow closely PDA No prenatal care Not optimal timing of the delivery High risk for PIVH a NEC Patency High risk for deterioration How treat PDA Indomethacín - preventon of PIVH III, IV , prevencia NEC Ibuprofen - prevencia NEC Paralen ? Surgical ligation Necrotising enterocolitis (NEC) Age at diagnosis is inversely related to gestational age and degree of prematurity Gestational age* Age at onset Pathophysiology of NEC < 30 weeks 20.2 days 31-33 weeks 13.8 days > 34 weeks 5.4 days Full term 1-3 days Diagnosis of NEC: High index of suspicion based on history and physical findings Early appearances are subtle and easily confused with neonatal sepsis. o Apnea (pause in breathing) o Bradycardia (slowing of heart rate) o Lethargy o Temperature instability Diagnosis and Staging of NEC: Later signs reflect progression of illness: Palpable mass, Hypotension, Bleeding disorders, Acidosis, Abdominal tenderness, Abdominal wall erythema, Peritonitis, Ascites The best prevention of NEC Use only colostrum or mother milk Start with a feeding as soon as possible (also in very small babies) Care about the babies together with mothers Support the healthy gut flora, support the microbiome Neonatal hypocalcemia - Ca-P imbalance occurs - Insufficient intake - Excessive losses - Long-term TPN Early onset neonatal hypocalcemia (ENH) (48-72h) - occurs in the first 3 days of life - Premature newborns- increased risk- gestational week less than 32 Etiology Decreased intake, hypoalbuminemia, decreased response to vit. D Interruption of transplacental Ca supply rapid postnatal decline in calcaemia Reduced target organ response to parathyroid hormone Clinically- often asymptomatic, symptoms- lethargy, inadequate food intake, vomiting, abdominal distension Late onset neonatal hypocalcemia (LNH) - Rarely - usually symptomatic- neonatal tetany - aetiology- phosphate-rich formula/ cow's milk, hypoparathyroidism - In prematurity can lead to pathological fractures of long bones and ribs Prematurity hearing impairment - 1-5/ 100 newborns at risk, occurs as a consequence of hypoperfusion - Prenatal- CMV, rubella, toxoplasmosis, syphilis, HSV, toxic substances - Perinatal- hyperbilirubinemia (unconjugated), asphyxia, prematurity, hypotrophy, infections, ototoxic ATB- aminoglycosides (streptomycin, neomycin, kanamycin, gentamycin, viomycin, polymyxin B) Accumulation in the inner ear, destroys outer and later inner hair cells and lesions the striae vascularis and ganglion cells - Postnatal- meningitis, inf. diseases, head trauma, noise, diseases of the auditory organ - Newborn hearing screening- OAE, higher. stem evoked potentials 4a. Bronchial Asthma: Asthma: Definition: - Asthma is a chronic inflammatory disease of the respiratory system characterized by: o Bronchial hyperresponsiveness (airways constricting in response to triggers) o Episodic respiratory symptoms o Reversible airflow obstruction - Asthma usually develops in childhood and is triggered by allergens such as pollen, dust mites, and certain foods. Epidemiology: - High prevalence in some countries – around 10% of children o Prevalence is increasing over the world - Asthma is the most common chronic disease of childhood in industrialized countries, affecting nearly 7 million children younger than 18 years of age in US. Classification: - Intermittent asthma - Mild persistent asthma - Moderate persistent asthma - Severe persistent asthma Asthma endotypes type 2 high: eosinophilic inflammation (IL-4, IL-5, IL-9, IL-13), more common type 2 low: neutrophilic inflammation (IL−17, IL-6, IL-21, IL-22), less common, often severe and resistant to therapy Asthma phenotypes in childhood 1) Transient 2) persistent a. Linked with smoking i. Non-atopic during pregnancy a. Ssociated with viral RTIs (RSV) b. Viral RTIs b. May remit during school age c. Not associated wit atopy c. Variable response to bronchodilators d. Remits by school age ii. Atopic e. Impaired lung function at a. Bronchial responsiveness, impaired birth lung function f. Variable response to b. Parental history of asthma bronchodilators c. most ongoing during school age Etiology: d. good response to bronchodilators - Exact etiology of asthma remains unknown – some environmental trigger in agenetically susceptible individual – polygenic association! o “Double hit”- Atopic sensitization + viral infection (eg. human rhinovirus 3) - Known risk factors include: o Family history of asthma o Past history of allergies o Atopy – genetic predisp. to produce IgE o Low socioeconomic status o Second-hand smoking - Triggering factors: o Dust mites, mold spores o Domestic animals with fur o Air pollution o Cockroaches o Pollen o Occupational irritants Pathogenesis: - Presentation of allergens by antigen-presenting cells leads to stimulation of Th2-cells which activates B cells, mast cells and eosinophils. o This activation leads to release of factors such as histamine, leukotrienes, prostaglandins, cytokines and basic proteins and enzymes. - Asthma consists of the following three pathophysiological processes: 1) Bronchial hyperresponsiveness 2) Bronchial inflammation – inhalation of antigen leads to bronchialsubmucosal edema and smooth muscle contraction 3) Endobronchial obstructions due to bronchospasm, edema, hypertrophyof smooth muscle cells and increased mucus production Clinical features: - Children with asthma have symptoms like: o Coughing o Recurring episodes of wheezing o Breathlessness o Chest tightness These signs are particularly occurring at night or early in the morning. - Physical signs – according to severity o Cyanosis, drowsiness, difficulty speaking o Tachycardia, hyperinflated chest o Use of accessory muscles o Intercostal retractions Acute asthma attacks – acute, reversible episode of lower airway obstruction thatmay be life- threatening: o Tachypnea, tachycardia, cough, wheezing and prolonged expiration o As attack progresses, cyanosis, retractions, agitation, inability to speak,diaphoresis and pulsus paradoxus may be observed o Increase in PCO2 (hypercapnia), Decrease in O2 saturation  Comorbid conditions: Eczema/atopic dermatitis Allergic rhinitis  colds, ear infections  sneezing in the morning  blocked nose, snoring, mouth breathing Allergic conjunctivitis  ocular itching  eyelid swelling  tearing, watery discharge  foreign body sensation Gastro-esophageal reflux (GER)  Nocturnal cough followed by vomiting Diagnosis: - History: o A combination of history, clinical findings and pulmonary function tests areneeded to confirm the diagnosis and assess the severity of asthma o What features one should look for specifically? ▪ Dyspnea: Expiratory wheeze, Accessory muscle movement, Difficulty in feeding, talking, getting to sleep, Irritability ▪ Cough: Persistent/ recurrent / nocturnal/ exercise-induced ▪ Associated conditions: Eczema, Allergic rhinitis, Allergic conjunctivitis - Clinical examination: o Auscultation: ▪ Characteristic findings are usually present during acute attacks  Prolonged expiration with wheezing – expiratory wheezing!  Decreased breath sounds – possibly ‘silent chest’  Tachypnea o In severe attacks: ▪ Altered level of consciousness, cyanosis - Pulmonary function tests: o PEFR – peak expiratory flow rate It is highly suggestive of asthma when: ▪ >15% increase in PEFR after inhaled short acting β2 agonist ▪ >15% decrease in PEFR after exercise ▪ Diurnal variation > 10% in children not on bronchodilator o Spirometry: ▪ Reversibility testing (broncholysis): an increase in FEV1 (≥ 12%) after administration of a bronchodilator indicates reversible airflow limitation consistent with asthma.  ▪ Challenge tests (provocation): specific (allergen) or non-specific (histamin, exercise) test to assess airflow limitation (decrease in FEV1) ▪ First-line diagnostic test for confirmation of the diagnosis in patients > 5 years of age (Difficult to tell children 12% increase in FE - FeNO (fractional exhaled nitric oxide) testing o NO is produced by inflammatory cells in asthma o Exhaled NO reflects airway inflammation and can be used in diagnostics and monitoring of asthma. - Specific/non-specific challenge tests: o Methacholine challenge test – bronchoprovocation test – second-line ▪ Evidence of bronchial hyperresponsiveness after inhalation of methacholine – Positive if FEV1 is reduced > 20% - Chest X-ray: o Usually indicated in patients with severe asthma to exclude diff. diagnoses(e.g. pneumonia, pneumothorax) ▪ In severe cases – signs of hyperinflation; low, flattened diaphragm,wide intercostal spaces - Laboratory: o Pulse oximetry and ABG: ▪ Blood gas analysis should be performed if SpO2 is < 94% ▪ Findings on ABG:  Initially – Decreased pCO2, Increased pH, decreased pO2 o Type 1 respiratory failure (due to tachypnea)  Ultimately – Increased pCO2, Decreased pH, big decreased inpO2: o Type 2 respiratory failure (due to respiratory fatigue) o Immunoglobulins: Check for specific or total IgE - Allergic asthma: o Skin prick testing Treatment: - Non-specific management: o AVOID triggers o Healthy nutrition o Regular exercise - Pharmacotherapy: o Drugs for asthma: ▪ Short term relievers – used at the time of acute attacks:  Immediate reversal of bronchospasms, but no effect on underlying inflammation: o Short-acting beta-2 agonists o Anticholinergics ▪ Long term relievers – taken regularly on a long term basis:  To control degree of inflammation and bring improvement of overall asthma control: o Corticosteroids – INHALED CSs o Long-acting beta-2 agonists o Leukotriene modifiers o Methyl xanthines ▪ New modalities:  Monoclonal anti-IgE – not frequently used  Specific immunotherapy  General about pharmacological asthma management: o Asthma management in children is a STEP-BY-STEP approach in treatment,in which we build up the treatment according to how symptoms are controlled. ▪ Asthma control test:  The patient describes during the past 4 weeks how he/she has been feeling – based on the score outcome it is possible to seeif the control of asthma is satisfactory or not.  The test includes questions about symptom frequency, time ofoccurrence, etc. Classification of asthma control Intermittent Asthma Moderate Persistent Asthma − Symptoms less than once a − Symptoms daily week − Exacerbations may affect − Brief exacerbations activity and sleep − Nocturnal symptoms not more − Nocturnal symptoms more than than twice a month once a week − Daily use of inhaled SABA Mild Persistent Asthma (short-acting 2-agonist) − Symptoms more than once a week but less than once a day Severe Persistent Asthma − Exacerbations may affect − Symptoms daily activity and sleep − Frequent exacerbations − Nocturnal symptoms more than − Frequent nocturnal asthma twice a month symptoms − Limitation of physical activities - Severity of asthma exacerbations: o Mild o Moderate o Severe Asthma exacerbation treatment: o Inhaled rapid-acting beta-2 agonists – metered dose inhaler ▪ 2-4 puffs of salbutamol via spacer, every 10-20 minutes for one hour  If not sufficient – hospitalization is required. o Inhaled rapid-acting beta-2 agonists – nebulization: ▪ 2.5-5mg salbutamol via nebulizer, every 20-30 minutes  o Supplementary ipratropium bromide: ▪ 250 ug/dose, every 20-30 minutes o Oral/parenteral glucocorticoids: ▪ 1-2mg/kg/day o Oxygen supplementation, Fluid replacement Drug list: - Beta-2-agonists: SABA (Albuterol, Terbutaline), LABA (Sameterol, Formoterol) - Inhaled CS: Beclomethasone, Fluticasone, Budesonide etc. - Oral CS: Methylpredisolone, Prednisone - Leukotriene modifiers: Montelukast, Zafirlukast, Zileuton - Muscarinic antagonist: Ipratropium, Tiotropium - Biologicals: Omalizumab (Anti-IgE), Mepolizumab (anti-IL-5) - Methylxanthines: Theophylline (inhibits phosphodiesterases) - Mast-cell stabilizers: Cromolyn, Nedocromil (prevents degranulation) Complications of asthma: - Status asthmaticus: o Extreme asthma exacerbation that does not respond to initial treatment with bronchodilators. Initially presents with tachypnea, tachycardia, hypoxemia and cyanosis, as well as hypercarbia. Signs of imminent respiratory arrest includes drowsiness/confusion, paradoxical thoracoabdominal movement, bradycardia, absent wheezing and pulsus paradoxus. Diagnosed based on ABG and Peak expiratory flow measurement. Management include hospitalization with supplemental oxygen or noninvasive ventilation ▪ Medications:  SABA, SAMA (Ipratropium bromine), Oral corticosteroid  Intravenous magnesium sulfate 4b. Differential diagnosis of hematuria Hematuria: - The definition of hematuria is based on microscopic examination of freshmidstream urine sediment – more than 5 RBC/visual field Classified into: - Microscopic – not grossly visible (more frequent) o Usually glomerular in origin - Macroscopic – grossly visible o Usually non-glomerular in origin Morphology of the RBCs – by urine phase contrast microscopy - Identifies the origin of hematuria: o RBCs from the lower urinary tract maintain their morphology ▪ Normal RBCs in urine = Lower urinary tract o Glomerular hematuria is characterized by dysmorphic RBCs ( > 5-12% acanthocytes) ▪ Acanthocytic/abnormal RBCs in urine = Glomerular origin Etiology of hematuria: - Prerenal: o Due to bleeding disorders (e.g. thrombocytopenia, hemophilia, drugs etc.) - Renal: o Glomerular origin: ▪ Acute PSGN ▪ IgA nephropathy:  Primary: Berger disease  Secondary: HS purpura ▪ Alport syndrome, Thin basement membrane nephropathy ▪ Other GN, SLE, MPGN... o Non-glomerular: ▪ Hypercalciuria, calcium-stones