Ghai Essential Pediatrics PDF

Eighth Edition  Contents Preface to the Eighth Edition vii 7. Micronutrients in Preface to the First Edition ix Health and Disease 110 List of Contributors...

Eighth Edition  Contents Preface to the Eighth Edition vii 7. Micronutrients in Preface to the First Edition ix Health and Disease 110 List of Contributors xi Ashima Gulati, Arvind Bagga Fat soluble vitamins 110 1. Introduction to Pediatrics Water soluble vitamins 117 Minerals and trace elements 121 Vinod KPaul Pediatrics as a specialty Health system in India 2 8. Newborn Infants 124 National programs on child health 3 Ramesh Agarwal, V inod K Paul, Ashok K Deorari Resuscitation of a newborn 125 Routine care 133 2. Normal Growth and its Disorders 7 Thermal protection 143 Ramesh Agarwal, Naveen Sankhyan, Vandana Jain Fluid and electrolyte management 146 Somatic growth 11 Kangaroo mother care 148 Assessment of physical growth 11 Breastfeeding 150 Disorders of growth 35 Care of low birth weight babies 155 Abnormalities of head size and shape 39 Infections in the neonates 162 Perinatal asphyxia 166 3. Development 42 Respiratory distress 168 Ramesh Agarwal, Vandana Jain, Naveen Sankhyan Jaundice 172 Normal development 42 Congenital malformations 176 Behavioral disorders 57 Followup of high risk neonates 178 Habit disorders and tics 59 Metabolic disorders 179 Effect of maternal conditions on fetus and neonates 181 4. Adolescent Health and Development 63 9. Immunization and Immunodeficiency Tushar R Godbole. Vijayalakshmi Bhatia 184 Physical aspects 63 Aditi Sinha, Surjit Singh Cognitive and social development 63 Immunity 184 Problems faced by adolescents 65 Primary immunodeficiency disorders 185 Role of health care provider 67 Immunization 188 Commonly used vaccines 190 5. Fluid and Electrolyte Disturbances 70 Vaccine administration 203 Kamran Afzal Immunization programs 205 Composition of body fluids 70 Immunization in special circumstances 206 Deficit therapy 72 Sodium 73 10. Infections and Infestations 209 Potassium 76 Tanu Singha!, Rakesh Lodha, SK Ka bra Calcium 79 Fever 209 Magnesium 82 Common viral infections 213 Acid-base disorders 83 Viral hepatitis 220 Human immunodeficiency virus (HIV) 229 6. Nutrition 88 Common bacterial infections 240 V inod KPaul, Rakesh Lodha, Anuja Agarwala Tuberculosis 250 Macronutrients 88 Fungal infections 259 Normal diet 90 Protozoa! infections 260 Undernutrition 95 Congenital and perinatal infections 272 Management of malnutrition l 00 Helminthic infestations 273  ________ -....E s s e n t ia l P e d ia t ri c _s _________________________ ______________ 11. Diseases of Gastrointestinal System Rheumatic fever and rheumatic heart disease 433 Infective endocarditis 443 and Liver 278 Myocardial diseases 447 Anshu Srivastava, Barath Jagadisan, SK Yachha Pericardia! diseases 450 Gastrointestinal disorders 278 Systemic hypertension 451 Acute diarrhea 291 Pulmonary arterial hypertension 456 Persistent diarrhea 297 Rhythm disorders 457 Chronic diarrhea 299 Preventing adult cardiovascular disease 462 Gastrointestinal bleeding 306 Disorders of the hepatobiliary system 309 Acute viral hepatitis 312 16. Disorders of Kidney and Liver failure 313 Urinary Tract 464 Chronic liver disease 316 Arvind Bagga, Aditi Sinha, RN Srivastava Renal anatomy and physiology 464 12. Hematological Disorders 330 Diagnostic evaluation 467 Acute glomerulonephritis 474 Tulika Seth Nephrotic syndrome 477 Anemia 330 Chronic glomerulonephritis 483 Approach to hemolytic anemia 337 Urinary tract infections 483 Hematopoietic stem cell transplantation 347 Acute kidney injury 487 Approach to a bleeding child 349 Chronic kidney disease 493 Thrombotic disorders 355 Renal replacement therapy 497 Leukocytosis, leukopenia 357 Disorders of renal tubular transport 497 Enuresis 504 Congenital abnormalities of kidney and 13. Otolaryngology 359 urinary tract 505 Sandeep Samant, Grant T Rohman, Cystic kidney diseases 507 Jerome W T hompson Diseases of the ear 359 17. Endocrine and Metabolic Diseases of the nose and sinuses 363 Diseases of the oral cavity and pharynx 366 Disorders 510 Diseases of the larynx and trachea 368 PSN Menon, Anurag Bajpai, Kanika Ghai Diseases of the salivary glands 370 Disorders of pituitary gland 511 Disorders of thyroid gland 516 Disorders of calcium metabolism 521 14. Disorders of Respiratory System 371 Disorders of adrenal glands 523 SK Kabra Obesity 528 Disorders of the gonadal hormones 53 l Common respiratory symptoms 371 Diabetes mellitus 54 l Investigations for respiratory illness 373 Respiratory tract infections 374 Acute lower respiratory tract infections 376 18. Central Nervous System 549 Bronchial asthma 382 Veena Kalra Foreign body aspiration 391 Approach to neurological diagnosis 549 Lung abscess 391 Seizures 552 Bronchiectasis 392 Febrile convulsions 556 Cystic fibrosis 393 Epilepsy 557 Acute respiratory distress syndrome (ARDS) 393 Coma 561 Acute bacterial meningitis 563 Tuberculous meningitis 566 15. Disorders of Cardiovascular Encephalitis and encephalopathies 568 System 396 lntracranial space occupying lesions 570 Subdural effusion 573 R Krishna Kumar, R Tandon, Manu Raj Hydrocephalus 574 Congestive cardiac failure 396 Neural tube defects 575 Congenital heart disease 400 Acute hemiplegia of childhood 577 Acyanotic congenital heart defects 413 Paraplegia and quadriplegia 578 Cyanotic heart disease 420 Ataxia 579 Obstructive lesions 429 Cerebral palsy 581 ___________________________________:c:on :.:;t:: ent :.:. :s....J- Degenerative brain disorders 583 24. Eye Disorders 665 Mental retardation 584 Radhika Tandon Neurocutaneous syndromes 586 Pediatric eye screening 665 Congenital and developmental abnormalities 666 19. Neuromuscular Disorders 587 Acquired eye diseases 667 Sheffali Gulati 25. Skin Disorders 672 Approach to evaluation 587 Neena Khanna. Seemab Rasool Disorders affecting anterior horn cells 588 Basic principles 672 Peripheral neuropathies 589 Genodermatoses 675 Acute flaccid paralysis 592 Nevi 679 Neuromuscular junction disorders 593 Eczematous dermatitis 680 Muscle disorders 594 Disorders of skin appendages 682 Papulosquamous disorders 684 20. Childhood Malignancies 599 Disorders of pigmentation 686 Drug eruptions 686 Sadhna Shankar, Rachna Seth Infections 687 Leukemia 599 Diseases caused by arthropods 694 Lymphoma 608 Brain tumors 612 26. Poisonings, Injuries and Retlnoblastoma 614 Accidents 696 Neuroblastoma 616 P Ramesh Menon Wilms tumor 617 Soft tissue sarcoma 618 Poisoning 696 Bone tumors 619 Common poisonings 700 Malignant tumors of the liver 620 Envenomation 703 Histiocytoses 620 Injuries and accidents 704 Oncologic emergencies 622 Hematopoietic stem cell transplantation 623 27. Pediatric Critical Care 708 Rakesh Lodha, Manjunatha Sarthi 21. Rheumatological Disorders 624 Assessment and monitoring of a seriously ill child 708 Surjit Singh Pediatric basic and advanced life support 71O Arthritis 624 Shock 715 Systemic lupus erythematosus 628 Mechanical ventilation 719 Juvenile dermatomyositis 629 Nutrition in critically ill children 720 Scleroderma 630 Sedation, analgesia and paralysis 721 Mixed connective tissue disease 630 Nosocomial infections in PICU 721 Vasculitides 631 Transfusions 723 22. Genetic Disorders 635 28. Common Medical Procedures 727 Sidharth Kumar Sethi. Arvind Bagga Neerja Gupta, Madhulika Kabra Obtaining blood specimens 727 Chromosomal disorders 636 Removal of aspirated foreign body 727 Single gene disorders 64 l Nasogastric tube insertion 728 Polygenic inheritance 644 Venous catheterization 728 Therapy for genetic disorders 644 Capillary blood (hell prick) 730 Prevention of genetic disorders 645 Umbilical vessel catheterization 730 Arterial catheterization 731 23. Inborn Errors of Metabolism 647 lntraosseous Infusion 731 Neerja Gupta, Madhulika Kabra Lumbar puncture 732 Thoracocentesis 733 Suspecting an inborn error of metabolism 647 Abdominal paracentesis or ascitic tip 734 Aminoacidopathies 652 Urea cycle defects 653 Catheterization of bladder 734 Organic acidurias 655 Peritoneal dialysis 734 Defects of carbohydrate metabolism 655 Bone marrow aspiration and biopsy 736 Mitochondial fatty acid oxidation defects 657 Liver biopsy 737 Lysosomal storage disorders 659 Renal biopsy 738  E s s e n ti a i Pe d i a tr ic s ________________________________ ___ ______________ 29. Rational Drug Therapy 739 Outpatient management of sick child age 2 months upto 5 years 758 Anu Thukral, Ashok K Deorari Revision in IMNCI guidelines 767 30. Integrated Management of Neonatal 31. Rights of Children 768 and Childhood Illness 751 Rajeev Seth AK Patwari, S Aneja Child abuse and neglect 769 IMNCI strategy 751 Adoption 770 Outpatient management of young infants age up to 2 months 752 Index 773  Introduction to Pediatrics Vinod K Paul The branch of medicine that deals with the care of children neurology, hematooncology, endocrinology and cardiology). and adolescents is pediatrics. This term has roots in the Pediatrics covers intensive care of neonates and children Greek word pedo pais (a child) and iatros (healer). Pediatrics using the most sophisticated technology, on the one hand, covers the age group less than 18 yr of age. A physician and providing home care to newborns and children, on the who specializes in health care of children and adolescents other. Child health is thus a state-of-art clinical science as is a pediatrician. The goal of the specialty is to enable a child well as a rich public health discipline. to survive, remain healthy, and attain the highest possible Medical students should possess competencies for the potential of growth, development and intellectual care of healthy and sick children. The agenda of high child achievement. Child health encompasses approaches, mortality due to pneumonia, neonatal infections, preterm interventions and strategies that preserve, protect, promote birth complications, diarrhea, birth asphyxia and vaccine and restore health of children at individual and population preventable diseases is still unfinished. The benefits of level. advancing pediatric specialties must reach all children. Children under 15 yr of age comprise about 30% of India's Besides, an increasing body of knowledge on pediatric population. Childhood is the state when the human being origins of noncommunicable diseases of the adult is set to is growing and developing. It is time to acquire habits, change the paradigm of child health. Primary prevention, values and lifestyles that would make children responsible identification of early markers and timely treatment of adult adults and citizens. The family, society and nation are duty­ disorders are the emerging imperatives in pediatrics. bound to make children feel secure, cared for, and protected from exploitation, violence and societal ills. Female children Historical Perspective face gender bias in access to healthcare and nutrition. A civilized society nurtures all its children, girls and boys Medical care of children finds place in the ancient Indian, alike, with love, generosity and benevolence. Greek and Chinese systems of health. But as a formal Child is not a miniature adult. The principles of adult discipline, pediatrics took root in Europe and the US in the medicine cannot be directly adapted to children. Pediatric 19th century when some of the famous children hospitals biology is unique and risk factors of pediatric disease are were established. BJ Hospital for Children, Mumbai was distinct. Clinical manifestations of childhood diseases may the first child hospital to be established in India in 1928. be different from adults. Indeed, many disorders are unique Postgraduate diploma in pediatrics was started there in to children. Drug dosages in children are specific and not a 1944; postgraduate degree programs began in the fifties. mathematical derivation of the adult doses. Nutrition is a Pediatrics became an independent subject in MBBS course critical necessity for children not only to sustain life, but to in mid-nineties. The first DM program in neonatology ensure their growth and development. started in 1989 at PGIMER, Chandigarh and in pediatric neurology at AIIMS in 2004. Pediatrics as a Specialty Pediatrics is a fascinating specialty. It encompasses care of Challenge of High Child Mortality premature neonates on the one hand, and adolescents, on India has the highest number of child births as well as the other. The discipline of pediatrics has branched into well­ child deaths for any single nation in the world. Each year, developed superspecialties (such as neonatology, as many as 27 million babies are born in the country. This nephrology, pulmonology, infectious disease, critical care, comprises 20% of the global birth cohort. Of the 7.8 million 1 ___e_s_s_e_n__ ai t__ l P_ _de _ _· c _tai _ s n ---------------------------------- under 5 child deaths in the world in 2010, 1.7 million (23%) Reduction in infant mortality is the foremost occur in our country. The mortality risk is highest in the development goal of the country. India is a signatory of neonatal period. National programs focus generally on the millennium declaration and thereby committed to the child deaths under the age of 5 yr (under-5 mortality). Millennium Development Goals (MDC). The MDC Table 1.1 provides the most recent figures on the key child 4 encompasses reduction of U5MR by two-thirds by 2015 mortality indices. from the 1990 baseline. Since the U5MR in 1990 was 117 per 1000 live births, the MDC 4 goal is to attain U5MR Table 1.1: Child mortality indices in India of 39 per 1000 live births by 2015. This corresponds to an IMR of 29 per 1000 live births. Given the prevailing levels Indices Level in 2012 (Fig. 1.1), India would have to further accelerate her child Under 5 mortality rate (USMR) 52 per 1000 live births survival action to attain MDC 4. This is difficult, but Infant mortality rate (IMR) 42 per 1000 live births achievable. The XII Plan aims to bring IMR to 25 per 1000 Neonatal mortality rate (NMR) 29 per 1000 live births live births by 2017. Early neonatal mortality rate (ENMR) 23 per 1000 live births USMR Number of deaths under the age of 5 years per 1000 live births Why do children die? !MR Number of deaths under the age of 1 year per 1000 live births The eight important causes of under 5 mortality in children NMR Number of deaths under the age of 28 days per 1000 live births in India are: (i) pneumonia (24%), (ii) complications of ENMR Number of deaths under the age of 7 days per 1000 live births prematurity (18%), (iii) diarrhea (11%), (iv) birth asphyxia (10%), (v) neonatal sepsis (8%), (vi) congenital anomalies In terms of under 5 mortality (U5MR), India ranks 46th (4%), (vii) measles (3%), and (viii) injuries (3%) (Fig. 1.2). among 193 countries. The U5MR in India (52 per 1000 live The above causes are the proximate conditions that lead births) is unacceptably high given our stature as an to death. Poverty, illiteracy, low caste, rural habitat, economic, scientific and strategic power. U5MR in Japan harmful cultural practices, and poor access to safe water (3), UK (5), USA (8), Sri Lanka (17), China (18) and Brazil and sanitation are important determinants of child health. (19) is worth comparing with that of India. Great nations Undernutrition is a critical underlying intermediate risk not only have negligible child mortality, but also ensure factor of child mortality, associated with 35% of under 5 good health, nutrition, education and opportunities to child deaths. Undernutrition causes stunting and wasting, their children. Majority (56%) of under 5 deaths occur in predisposes to infections and is associated with adult the neonatal period (20 U [Na] 20 U [Na ] >20 u [Na] 25 mEq/1 in the first 24-48 hr) intracranial hemorrhage; slowly developing hypematremia of chronic hyponatremia. Clinical features include mutism, dysarthria, spastic quadriplegia, ataxia, pseudo­ Table 5.6: Causes of hypernatremia bulbar palsy, altered mental status, seizures and Net water loss hypotension. Pure water loss Fluid restriction alone has no role in the management Insensible losses of symptomatic hyponatremia. Normal saline is also Diabetes insipidus inappropriate for treating hyponatremic encephalopathy Inadequate breastfeeding due to non-hemodynamic states of vasopressin excess, Hypotonic fluid loss such as SIADH and postoperative hyponatremia, as it is Renal: Loop, osmotic diuretics, postobstructive, polyuric phase not sufficiently hypertonic to induce reduction in cerebral of acute tubular necrosis edema. In presence of elevated ADH levels there is Gastrointestinal: Vomiting, nasogastric drainage, diarrhea; impaired ability to excrete free water with the urine lactulose osmolality exceeding that of plasma. V2-receptor anta­ Hypertonic sodium gain gonists or vaptans that block the binding of ADH to its Excess sodium intake V2 receptor, are yet not recommended for treatment of Sodium bicarbonate, saline infusion hyponatremic encephalopathy. These agents may have Hypertonic feeds, boiled skimmed milk a role in treating euvolemic hyponatremia from SIADH Ingestion of sodium chloride and hypervolemic hyponatremia in congestive heart Hypertonic dialysis failure. Endocrine: Primary hyperaldosteronism, Cushing syndrome  s --------------- __E_s_s_e_n_ti_a _i _P_e _d_ia_t_ri_c ----------------- is generally well tolerated. The latter adaptation occurs maintained predominantly through the regulation of renal initially by movement of electrolytes into cells and later excretion. The fractional excretion of potassium is about by intracellular generation of organic osmolytes, which 10%, chiefly regulated by aldosterone at the collecting duct. counter plasma hyperosmolarity. Renal adaptive mechanisms maintain potassium homeostasis until the glomerular filtration rate drops to less Treatment than 15-20 ml/min. Excretion is increased by aldosterone, Treatment involves restoring normal osmolality and high sodium delivery to the collecting duct (e.g. diuretics), volume and removal of excess sodium through the urine flow (e.g. osmotic diuresis), blood potassium level, administration of diuretics and hypotonic crystalloid glucocorticoids, ADH and delivery of negatively charged solutions. The speed of correction depends on the rate of ions to the collecting duct (e.g. bicarbonate). In renal failure, development of hypernatrernia and associated symptoms the proportion of potassium excreted through the gut (Box 5.2). Because chronic hypernatrernia is well tolerated, increases, chiefly by the colon in exchange for luminal rapid correction offers no advantage and may be harmful sodium. since it may result in brain edema. Usually a maximum of Aldosterone and insulin are two play important roles 10% of the serum sodium concentration or about 0.5 mEq/ in potassium homeostasis. Insulin stimulated by potassium 1/hr should be the goal rate of correction. Seizures due to ingestion increases uptake of potassium in muscle cells, hypernatremia are treated using 5-6 ml/kg infusion of through increased activity of the sodium pump. High 3% saline over 1-2 hr. potassium levels stimulate its renal secretion via aldos­ terone-mediated enhancement of distal expression of POTASSIUM ----- ------------- secretory potassium channels (ROMK). Insulin, beta­ adrenergic stimuli and alkalosis enhance potassium entry Physiology into cells. The reverse happens with glucagon, a-adrener­ Potassium being a predominantly intracellular cation, its gic stimuli and acidosis. blood levels are unsatisfactory indicator of total body stores. Normal serum concentration of potassium ranges Hypokalemia between 3.5 and 5 mEq/1. Common potassium-rich foods Hypokalernia is defined as a serum potassium level below include meats, beans, fruits and potatoes. Gastrointestinal 3.5 mEq/1. The primary pathogenetic mechanisms result­ absorption is complete and potassium homeostasis is ing in hypokalemia include increased losses, decreased intake or transcellular shift (Table 5.7). Vomiting, a Box 5.2: Treatment of hypernatrernia Treat hypotension first, regardless of serum sodium Table 5. 7: Causes of hypokalernia (normal saline bolus, Ringer lactate, 5% albumin) Correct deficit over 48 to 72 hr. Rapid decline of chronic Increased losses (>48 hr) hypematremia is associated with risk of cerebral Renal edema. Recommended rate of drop in serum sodium is Renal tubular acidosis (proximal or distal) 0.5 mEq/1/hr (10-12 mEq/1/ day) Drugs (loop and thiazide diuretics, amphotericin B, Oral solutions preferred to parenteral correction aminoglycosides, corticosteroids) Generally hypotonic infusates are used (infusate sodium Cystic fibrosis of - 40 mEq/1, as N/4 or N/5 saline). Sodium free fluids Gitelman syndrome, Bartter syndrome, Liddle syndrome should be avoided (except in acute onset hypematremia, Ureterosigmoidostomy e.g. sodium overload) Mineralocorticoid excess (Cushing syndrome, hyperal­ Decline of serum Na+ can be estimated using Adrogue­ dosteronism, congenital adrenal hyperplasia (11 P-hydroxy­ Madias Formula: lase, 17 o:-hydroxylase deficiency) High renin conditions (renin secreting tumors, renal artery + + Na Jinf+ (K+ Jinf- [Na L) stenosis) D[Na +J = {[ (TBW + 1) Extrarenal Where [Na+] expected change in serum sodium; [Na+] inf Diarrhea, vomiting, nasogastric suction, sweating sodium and [K+]infpotassium in 1 liter of the infusate, [Na+Js Potassium binding resins (sodium polystyrene sulfonate) serum sodium; TBW or total body water = 0.6 x body weight Decreased intake or stores Seizures due to hypematremia are treated using hypertonic Malnutrition, anorexia nervosa (3%) saline at 5-6 ml/kg infusion over 1-2 hr. Potassium-poor parenteral nutrition Renal replacement therapy (peritoneal or hemodialysis, hemofiltration) is indicated for significant hypematremia Intracellular shift (> 180-200 mEq/1) with concurrent renal failure and/ or Alkalosis, high insulin state, medications (P2-adrenergic volume overload. agonists, theophylline, barium, hydroxychloroquine), Ensure correction of ongoing fluid losses; frequent bio­ refeeding syndrome, hypokalemic periodic paralysis, chemical and clinical reassessment is needed. malignant hyperthermia, thyrotoxic periodic paralysis  Fluid and Electrolyte Disturbances - common cause of hypokalemia, produces volume deple­ tension such as congenital adrenal hyperplasia, gluco­ tion and metabolic alkalosis. Volume depletion leads to corticoid remediable hypertension or Liddle syndrome. secondary hyperaldosteronism, which enhances sodium Relative hypotension and alkalosis suggests diuretic use, or resorption and potassium secretion in the cortical collecting a tubular disorder such as Bartter or Gitelman syndrome. tubules. Metabolic alkalosis also increases potassium Therapy involves decreasing ongoing losses (e.g. secretion due to the decreased availability of hydrogen ions discontinuation of diuretics, -agonists), replenishing for secretion in response to sodium resorption. potassium stores (oral or intravenous administration of Regardless of the cause, hypokalemia produces similar potassium chloride) and disease-specific therapy for the signs and symptoms. Symptoms are nonspecific and conditions such as Bartter and Gitelman syndrome (e.g. predominantly are related to muscular or cardiac function. indomethacin, angiotensin-converting enzyme inhibitors) Severe hypokalemia ( 7.0 mEq/1) or the patient is symptomatic with sample. Thrombocytosis and leukocytosis can also lead ECG changes, therapy should be initiated promptly with to false elevation of serum potassium levels. True hyper­ intravenous calcium gluconate, followed by sodium kalemia is caused by one or more of 3 mechanisms: bicarbonate, insulin-glucose infusion and/or nebulized increased potassium intake, extracellular potassium shifts 2 -agonists. Hemodialysis may be needed in the more or decreased excretion (Table 5.8). Increased potassium refractory patients. Milder elevations (5.5-6.5 mEq/1) are intake may result from inappropriate intravenous or oral managed with elimination of potassium intake, dis­ potassium supplementation. Packed red blood cells have continuation of potassium sparing drugs and treatment high concentrations of potassium that can lead to of the underlying etiology. Children with primary or hyperkalernia. Acidosis results in transcellular potassium secondary hypoaldosteronism require stress-dose steroid shift, but any cellular injury that disrupts the cell mem­ supplements and mineralocorticoids. brane (e.g. tumor lysis syndrome, rhabdomyolysis, crush injury, massive hemolysis) can cause hyperkalemia. Sox 5.4: Treatment of hyperkalemia Patients may report nausea, vomiting and paresthesias Prompt discontinuation of potassium-containing fluids or nonspecific findings of muscle weakness (skeletal, and medications that lead to hyperkalemia respiratory), fatigue and ileus. Clinical manifestations are Stabilize the myocardial cell membrane to prevent lethal related to the effects of elevated potassium levels on cardiac cardiac arrhythmia. Use intravenous (IV) 10% calcium conduction since they interfere with repolarization of the gluconate (or calcium chloride), at 0.5 ml/kg over 5-10 cellular membrane. ECG changes appear progressively minutes under cardiac monitoring. Discontinue if bradycardia develops Table 5.8: Causes of hyperkalemia Enhance cellular uptake of potassium Regular insulin and glucose IV: (0.3 D regular insulin/g Decreased losses glucose over 2 hr) Renal failure Sodium bicarbonate IV: 1-2 mEq/kg body weight over Renal tubular disorders: Pseudohypoaldosteronism, urinary 20-30 minutes tract obstruction Beta-adrenergic agonists, such as salbutamol and Drugs: ACE inhibitors, angiotensin receptor blockers, terbutaline nebulized or IV potassium sparing diuretics, NSAIDS, heparin Ensure total body potassium elimination Mineralocorticoid deficiency: Addison disease, 21-hydroxylase Sodium polystyrene sulfonate (Kayexalate) oral/per deficiency, 3P-hydroxysteroid dehydrogenase deficiency rectal: 1 g/kg (max. 15 g/dose) oral or as rectal enema in Increased intake 20-30% sorbitol Intravenous or oral potassium intake; packed red cells Loop or thiazide diuretics (only if renal function is transfusion maintained) Extracellular shift Hemodialysis is necessary to treat severe symptomatic hyperkalemia that is resistant to drug therapy, particularly Acidosis, low insulin state, medications (P-adrenergic blockers, in patients with impaired renal functions. Continuous digitalis, succinylcholine, fluoride), hyperkalemic periodic veno-venous hemofiltration with dialysis (CVVHDF) have paralysis, malignant hyperthermia also been used to remove potassium Cellular breakdown Children with primary or secondary hypoaldosteronism Tumor lysis syndrome, rhabdomyolysis, crush injury, massive require maintenance steroids and mineralocorticoid hemolysis supplements  Fluid and Electrolyte Disturbances - CALCIUM growth hormone, adrenal and gonadal steroids also have minor influences on calcium metabolism. Physiology Role of the calcium-sensing receptor. The calcium-sensing Ninety-eight percent of body calcium is found in the receptor (CaSR) is a G protein-coupled receptor, which skeleton which is in equilibrium with the extracellular allows the parathyroid chief cells, the thyroidal C cells concentration of calcium. Approximately 1 to 2% of body and the ascending limb of the loop of Henle (renal tubular calcium exists in the ECF for physiological functions like epithelial cells) to respond to changes in the extracellular blood coagulation, cellular communication, exocytosis, calcium concentration. The ability of the CaSR to sense endocytosis, muscle contraction and neuromuscular the serum calcium is essential for the appropriate transmission. Calcium affects the intracellular processes, regulation of PTH secretion by the parathyroid glands and through its calcium-binding regulatory protein, calmodulin. for the regulation of passive paracellular calcium Most of the filtered calcium is reabsorbed in the absorption in the loop of Henle. Calcitonin secretion and proximal tubule (70%), ascending loop of Henle (20%) and renal tubular calcium reabsorption are directly regulated the distal tubule and collecting duct (5-10%). Factors that by the action of calcium ion on its receptor. Ionized calcium promote calcium reabsorption include parathormone acts through calcitonin, to inhibit its release from bones. (PTH), calcitonin, vitamin D, thiazide diuretics and Decrease in extracellular calcium concentration, stimulates volume depletion. Volume expansion, increased sodium the CaSR in parathyroid glands, resulting in an increase intake and diuretics such as mannitol and frusemide in PTH secretion (Fig. 5.7). PTH increases distal renal promote calcium excretion. tubular reabsorption of calcium within minutes and The intestine serves as a longterm homeostatic stimulates osteoclast activity, with release of calcium from mechanism for calcium. Although the major source of the skeleton within 1-2 hr. More prolonged PTH elevation calcium is dietary, less than 15% of dietary calcium is stimulates la-hydroxylase activity in the proximal tubular absorbed, primarily in the ileum and jejunum by means cells, which leads to 1, 25-dihydroxy-vitamin D production. of active transport and facilitated diffusion. Calcium is In the kidney, vitamin D and PTH stimulate the activity controlled primarily by major regulatory hormones, PTH, of the epithelial calcium channel and the calcium-binding calcitonin and vitamin D. Additionally thyroid hormones, protein (i.e. calbindin) to increase active transcellular l Decreased plasma calcium 7-dehydrocholesterol in Dietary skin Vit D2 (ergocalciferol) Vit D3 (cho alciferol) r 1 I { {{ff·,fr - i------ Fig. 5.7: Regulation of plasma calcium. Reduction in ionized calcium results in parathormone secretion, which through direct and indirect actions on the bones, intestine and the kidneys results in positive calcium balance. Calcitonin results in accretion of bone mass. Discontinuous lines indicate inhibitory control  l s ________________ __E_s_s_ e_n_t_ia_ _P_e _d_ia_t _ri_c_ __________________ calcium absorption in the distal convoluted tubule. These and algorithm for investigating the etiology are shown in mechanisms help to maintain normal levels of serum Table 5.9 and Fig. 5.8. Hypocalcemia manifests as central calcium. nervous system irritability and poor muscular contractility. Plasma calcium exists in 3 different forms: 50% as Newborns present with nonspecific symptoms such as biologically active ionized form, 45% bound to plasma lethargy, poor feeding, jitteriness, vomiting, abdominal proteins (mainly albumin) and 5% complexed to phosphate distension and seizures. Children may develop seizures, and citrate. In the absence of alkalosis or acidosis, the twitching, cramps and rarely laryngospasm (Box 5.5). proportion of albumin-bound calcium remains relatively Tetany and signs of nerve irritability may manifest as constant. Metabolic acidosis leads to increased ionized muscular twitching, carpopedal spasm and stridor. Latent calcium from reduced protein binding and alkalosis has tetany can be diagnosed clinically by clinical maneuvers the opposite effect. Plasma calcium is tightly regulated such as Chvostek sign (twitching of the orbicularis oculi despite its large movements across the gut, bone, kidney and cells in the normal range of 9-11 mg/dl. Table 5. 9: Causes of hypocalcemia Because calcium binds to albumin and only the unbound (free or ionized) calcium is biologically active, the serum Neonatal: Early (within 48-72 hr after birth) or late (3-7 days level must be adjusted for abnormal albumin levels. For after birth) neonatal hypocalcemia; prematurity; infant of every 1 g/dl drop in serum albumin below 4 g/dl, measured diabetic mother; neonates fed high phosphate milk serum calcium decreases by 0.8 mg/dl. Corrected calcium Parathyroid: Aplasia or hypoplasia of parathyroid glands, can be calculated using the following formula: DiGeorge syndrome, idiopathic; pseudohypoparathyroidism; autoimmune parathyroiditis; activating mutations of calcium Corrected Ca = sensing receptors [4 - plasma albumin in g/ dl] x 0.8 + measured serum calcium Vitamin D: Deficiency; resistance to vitamin D action; acquired Alternatively, serum free (ionized) calcium levels can or inherited disorders of vitamin D metabolism be directly measured, negating the need for correction Others: Hypomagnesernia; hyperphosphatemia (excess intake, for albumin. renal failure); malabsorption syndromes; idiopathic hypercalciuria; renal tubular acidosis; metabolic alkalosis; Hypocalcema i hypoproteinemia; acute pancreatitis Drugs: Prolonged therapy with frusernide, corticosteroid or Hypocalcemia is defined as serum calcium less than phenytoin 8 mg/dl or ionized calcium below 4 mg/dl. The causes Low serum calcium Correct for level of serum albumin; measure ionized calcium Normal J_ Low + No action] Serum magnesium Normal Low J Serum phosph Correct hypomagnesemia j + = + High Parathormone Low.r l?5(0H)D3 and 1,25(0H)2D3 levelsl I +L. --F + Hi + Low OH)D3 low ll 25(0H)D3 normal 1,25(0HhD3 1,25(0HhD3 low I high Renal failure ! +r Vitamin D + VDDR type I + VDDR type II Pseudohypoparathyroidism deficiency Renal failure Tumor lysis Fig. 5.8: Algorithm for evaluation of hypocalcemia. VDDR vitamin D dependent rickets  Fluid and Electrolyte Disturbances - Box. 5.5: Clinical features of hypocalcemia tightly controlled by the body, even mild persistent Carpopedal and muscle spasms elevations should be investigated. Etiologies of hyper­ Tetany calcemia vary by age and other factors (Table 5.10). Laryngospasm Hypercalcemia is often asymptomatic, although it can cause Paresthesias symptoms at levels as low as 12 mg/dl and consistently at Seizures values above 15 mg/dl. Such high values are however, Irritability, depression, psychosis rarely encountered and present as stupor and coma. Intracranial hypertension Neonates may be asymptomatic or may have vomiting, Prolonged QTc interval hypotonia, hypertension or seizures. Clinical features in older children are summarized in Box 5.6 and include irritability, and mouth elicited by tapping the facial nerve anterior to Box 5.6: Clinical features of hypercalcemia the external auditory meatus) and the Trousseau sign Lethargy, confusion, Bradycardia, systemic (carpopedal spasm elicited by inflating a blood pressure depression, coma hypertension, headache cuff on the arm to a pressure above the systolic pressure Hyporeflexia Nephrocalcinosis, Muscle weakness nephrolithiasis for 3 min). ECG shows prolonged corrected QT interval Constipation Polyuria (QTc) to more than 0.45 seconds. Cardiac function may be Reduced QTc interval impaired because of poor muscle contractility. Prolonged hyp ocalcemia can present with features of rickets. malaise, headache, confusion, unsteady gait and proximal Management muscle weakness. Abdominal pain with paralytic ileus, nausea and vomiting and constipation are often observed. Tetany, laryngospasm and seizures must be treated Ectopic calcification can lead to symptoms of pancreatitis, immediately with 2 ml/kg of 10% calcium gluconate, with epigastric pain and vomiting. Ectopic calcification can administered IV slowly under cardiac monitoring. Calcium manifest as conjunctivitis or band keratopathy. Renal gluconate 10% (100 mg/ml) IV solution contains 9.8 mg/ manifestations due to renal stones and nephrocalcinosis can ml (0.45 mEq/ml) elemental calcium; calcium chloride 10% progress to renal failure, and polyuria and polydipsia occur (100 mg/ml) contains 27 mg/ml (1.4 mEq/ml). Initially IV due to nephrogenic diabetes insipidus. calcium boluses are given every 6 hr. Thereafter, oral calcium supplementation is provided at 40-80 mg/kg/ Treatment day. Oral calcium therapy is used in asymptomatic pati­ The initial treatment of hypercalcemia involves hydration ents and as followup to intravenous (IV) calcium therapy. to improve urinary calcium excretion. Rapid lowering of Intravenous infusion with calcium-containing solutions serum calcium can be expected with isotonic sodium can cause severe tissue necrosis; therefore integrity of the IV site should be ascertained before administering calcium Table 5.1 0: Causes of hypercalcemia through a peripheral vein. Rapid infusion of calcium­ containing solutions through arterial lines can cause Neonates arterial spasm and if administered via an umbilical artery Neonatal primary hyperparathyroidism, secondary hyper- catheter, intestinal necrosis. Magnesium administration parathyroidism is necessary to correct any hypomagnesemia because Familial hypocalciuric hypercalcemia hypocalcemia does not respond until the low magnesium Excessive supplementation of calcium William syndrome, hyp ophosphatasia, idiopathic infantile level is corrected. In patients with concurrent acidemia, hypercalcernia hypocalcemia should be corrected first. Acidemia increa­ ses the ionized calcium levels by displacing calcium from Older children albumin. If acidemia is corrected first, ionized calcium Hyperparathyroidism (parathyroid adenoma, autosomal levels decrease. dominant hereditary hyperparathyroidism, multiple endo­ Calcium carbonate is an oral supplement providing 40% crine neoplasia type 1) elemental calcium. Therapy with cholecalciferol is used Malignancies: Non-Hodgkin or Hodgkin lymphoma, Ewing in patients with vitamin D deficiency. Calcitriol, an active sarcoma, neuroblastoma, Langerhans cell histiocytosis, metabolic form of vitamin D (i.e. 1,25-dihydroxychole­ rhabdomyosarcoma calciferol) is administered in liver or renal disease. Granulomatous disease: Sarcoidosis, tuberculosis, Wegener disease, berylliosis Hypercalcemia Others: Vitamin Dor A intoxication; thiazide diuretics; milk­ alkali syndrome; dietary phosphate deficiency; subcutaneous Hyp ercalcemia is defined as a serum calcium level greater fat necrosis; thyrotoxicosis; prolonged immobilization than 11 mg/dl. Because calcium metabolism normally is  s -------- ___E_s_se _n_ t_i_a _l _P_e _d_ ia_t _r_ic_ -------------------------- chloride solution, because increasing sodium excretion gastrointestinal (diarrhea, vomiting, nasogastric suction) increases calcium excretion. Addition of a loop diuretic or renal (chronic use of thiazide diuretics, recovery phase inhibits tubular reabsorption of calcium but attention of acute tubular necrosis, Gitelman syndrome, familial should be paid to other electrolytes (e.g. magnesium, h ypomagnesemia-h ypercalci uria -nephrocalcinosis). potassium) during saline diuresis. Bisphosphonates serve Symptomatic magnesium depletion (occurs at levels below to block bone resorption and decrease serum calcium within 1.2 mg/dl) is often associated with multiple biochemical a couple of days but have not been used extensively in abnormalities, including hypokalemia, hypocalcemia and children. Pamidronate and etidronate have been used in metabolic acidosis. As a result, hypomagnesemia is the treatment of hypercalcemia due to malignancy, sometimes difficult to attribute solely to specific clinical immobilization and hyperparathyroidism but may cause manifestations. Hypomagnesemia often leads to hypo­ mineralization defects. calcemia, possibly by inhibition of PTH activity. Peritoneal dialysis or hemodialysis can be used in Neuromuscular manifestations of hypomagnesemia extreme situations, particularly in patients with renal include muscle weakness, tremors, seizures, paresthesias, failure. Calcimimetics (cinacalcet hydrochloride) change the tetany, positive Chvostek sign, Trousseau signs and configuration of the CaSR in a manner that makes it more nystagmus. Cardiovascular manifestations include sensitive to serum calcium. Its safety and efficacy in nonspecific T-wave changes, U-waves and prolonged QT pediatric population has yet to be substantiated. Surgical interval and arrhythmias. intervention may be needed in patients with hyper­ parathyroidism, particularly with recurrent renal stones or Treatment persistent serum calcium levels higher than 12.5 mg/dl. Therapy can be oral for patients with mild symptoms or Subtotal parathyroidectomy can be performed, or complete intravenous for patients with severe symptoms or those parathyroidectomy can be chosen with reimplantation of a unable to tolerate oral administration. Severe hypoma­ small amount of tissue in the forearm. gnesemia is treated with slow intravenous infusion of magnesium sulfate (50% solution) at a dose of 25-50 mg/kg MAGNESIUM (2.5-5.0 mg/kg of elemental magnesium). The dose is repeated every 6 hr, for a total of 2-3 doses. Doses need to be Physiology reduced in children with renal insufficiency. Oral replace­ Magnesium is the third-most abundant intracellular cation ment should be given in the asymptomatic patient, or those predominantly located in muscle and liver cells. Most requiring longterm replacement, preferably with a intracellular magnesium is bound to proteins; only sustained-release preparation to avoid diarrhea. Oral approximately 25% is exchangeable. magnesium preparation provide 5-7 mEq of magnesium per Magnesium plays a fundamental role in many functions tablet. Two to four tablets may be sufficient for mild, of the cell, including energy transfer and storage and nerve asymptomatic disease while severe cases require up to six conduction. Magnesium also plays important role in to eight tablets, to be taken daily in divided doses. Patients protein, carbohydrate, and fat metabolism, maintenance with renal magnesium wasting may benefit from diuretics of normal cell membrane function and regulation of PTH with magnesium-sparing properties, such as spironolactone secretion. and amiloride. Dietary sources include green leafy vegetables, cereals, Hypermognesemio nuts and meats. Absorption of magnesium takes place primarily in the small intestine and is inversely related to Serum magnesium >2.5 mg/dl is uncommon in children the amount of magnesium, calcium, phosphate and fat. and may be seen in the setting of renal insufficiency, PTH and glucocorticoids increase magnesium absorption. prolonged use of magnesium containing antacids or in Absorption is diminished in presence of substances that neonates born to mothers given magnesium sulfate as a complex with magnesium (free fatty acids, fiber, phytate, treatment for eclampsia. Symptoms of hypermagnesemia phosphate, oxalate); increased intestinal motility and are nonspecific at lower levels: nausea, vomiting, flushing, calcium also decrease magnesium absorption. Vitamin D lethargy, weakness and dizziness. At higher levels, deep and PTH enhance absorption. Renal excretion is the tendon reflexes are depressed which may progress to coma principal regulator of magnesium balance. Reabsorption and respiratory depression. Effects on the heart may result occurs chiefly in the thick ascending loop of Henle (70%) in prolongation of intervals on ECG or manifest as and to a smaller extent in the proximal (15%) and distal arrhythmias, complete heart block and asystole. (5-10%) tubules. Fractional excretion of magnesium exceeding 4% indicates renal magnesium wasting. Treatment In patients with mildly increased levels, the source of Hypomognesemio magnesium may simply be removed. Intravenous calcium Hypomagnesemia develops from decreased intake or directly antagonizes the cardiac and neuromuscular effects more commonly increased losses which could be of excess extracellular magnesium. Dialysis may be used  Fluid and Electrolyte Disturbances - for patients with severe hypermagnesemia and renal or loss of bicarbonate results in metabolic acidosis. If the impairment, or those with serious cardiovascular or reverse occurs, it results in metabolic alkalosis. The neuromuscular symptoms. principle mechanism for carbon dioxide handling is by the lungs. Hyperventilation results its CO2 washout and ACID-BASE DISORDERS drop in arterial pC02 (respiratory alkalosis), hypo­ ventilation has the opposite effect (respiratory acidosis). Regulation of Acid-Base Equilibrium When only one primary acid-base abnormality occurs and The body is sensitive to changes in blood pH level, as its compensatory mechanisms are activated, the disorder disturbances in acid-base homeostasis can result in is classified as simple acid-base disorder. A simple denaturation of proteins and inactivation of enzymes that algorithm for defining simple acid-base disorders is shown may be potentially fatal. Strong mechanisms exist to in Fig. 5.9. When a combination of disturbances occurs, regulate acid-base balance and maintain arterial pH (7.35 the disorder is classified as a mixed acid-base disorder. to 7.45), pC02 (35 to 45 mm Hg) and HC03-(20 to 28 mEq/1) The latter are suspected when the compensation in a given within a narrow range. patient differs from the predicted values in Table 5.11. Acidemia is defined as H +concentration exceeding In order to maintain body homeostasis, changes in pH 45 nmol/1 (pH 7.45) are resisted by a complex system of intracellular and define alkalemia. The disorders that cause acidemia or extracellular buffers. The first line of defense, are the alkalemia are termed as acidosis and alkalosis respectively. chemical buffers. In metabolic disorders the extracellular Metabolic activity results in production of two types of buffers rapidly titrate the addition of strong acids or bases. acids, carbonic acid (a volatile acid, derived from carbon Intracellular buffers chiefly accomplish the buffering of dioxide) and nonvolatile acids (including sulfuric acid, respiratory disorders. Secondary respiratory compen­ organic acids, uric acid and inorganic phosphates). sations to metabolic acid-base disorders occur within Accumulation of H + ions of nonvolatile acids due to excess minutes and is completed by 12 to 24 hr. In contrast production or inadequate buffering, failure to excrete H + secondary metabolic compensation of respiratory --, Blood pH Acidemia (l pH) t Lr IRespiratory acidosis Metabolic acido Respiratory alkalosis Metaboli Respiratory acidosis Metabolic acidosis Metabolic alkalosis with compensatory with compensatory with compensatory metabolic alkalosis respiratory alkalosis respiratory acidosis Fig. 5.9; Algorithm for simple acid-base disorders Table 5.11 : Compensation for primary acid-base disorders Disorder Primary event Compensation Expected Compensation Metabolic acidosis l [HC03-J l pC02 pC02 l by 1-1.5 mm Hg for 1 mEq/l l[HC03] Metabolic alkalosis t [HC03-J t pC02 pC02 t by 0.5-1 mm Hg for 1 mEq/1 t [HC03] Respiratory acidosis Acute (20 anion gap decreases by 2.5 mEq/1. mOsm/kg) with metabolic acidosis suggests the presence of osmotically active agents such as methanol, ethylene Metabolic Acidosis glycol or ethanol. Metabolic acidosis is an acid-base disorder characterized by a decrease in serum pH that results from either a loss Clinical Features in plasma bicarbonate concentration or an increase in Initially, patients with a metabolic acidosis develop a hydrogen ion concentration (Table 5.12). Primary meta­ compensatory tachypnea and hyperpnea, which may bolic acidosis is characterized by an arterial pH of less progress if the acidemia is severe, and the child can present than 7.35 due to a decrease in plasma bicarbonate in the with significant work of breathing and distress (Kussmaul absence of an elevated PaC02. If the measured PaC02 is breathing). An increase in H+ concentration results in pulmonary vasoconstriction, which raises pulmonary Table 5.12: Causes of metabolic acidosis artery pressure and pulmonary vascular resistance. Normal anion gap (hyperchloremic acidosis) Tachycardia is the most common cardiovascular effect Renal loss of bicarbonate seen with mild metabolic acidosis. Cerebral vasodilation Proximal (type 2) renal tubular acidosis, carbonic anhydrase occurs as a result of metabolic acidosis and may contribute inhibitors (e.g. acetazolamide), tubular damage due to drugs to an increase in intracranial pressure. Acidosis shifts the or toxins oxygen-hemoglobin dissociation curve to the right, Gastrointestinal bicarbonate loss decreasing hemoglobin's affinity for oxygen. During Diarrhea, ureteral sigmoidostomy, rectourethral fistula, metabolic acidosis, excess hydrogen ions move toward the fistula or drainage of small bowel or pancreas intracellular compartment and potassium moves out of the Decreased renal hydrogen ion excretion cell into the extracellular space. Untreated severe Renal tubular acidosis type 1 and type 4 (aldosterone metabolic acidosis may be associated with life-threatening deficiency) arrhythmias, myocardial depression, respiratory muscle Potassium sparing diuretics fatigue, seizures, shock and multiorgan failure. Increased hydrogen chloride production Parenteral alimentation, increased catabolisrn of lysine and Treatment arginine Ammonium chloride ingestion It is important to identify the cause of metabolic acidosis as most cases resolve with correction of the underlying Elevated anion gap disorder. The role of alkali therapy in acute metabolic Increased acid production/accumulation: Sepsis, shock, poisonings acidosis is limited. It is definitely indicated in some (ethanol, methanol, ethylene glycol); inborn errors of situations, e.g. salicylate poisoning, inborn errors of metabolism metabolism, or in those with pH below or equal to 7.0 or Ketoacidosis: Diabetic ketoacidosis, starvation [HC03-J less than 5 mEq/1, as severe acidosis can produce Exogenous acids: salicylates, iron, isoniazid, paraldehyde myocardial dysfunction. The amount of bicarbonate Failure of acid excretion: Acute or chronic renal failure required is: Body weight (kg) x base deficit x 0.3.  i _______ __E_s_s_ e_n_t_a_i_P_e _d_ia _t _ri_cs_ ___________________________ One ml of 7.5% sodium bicarbonate provides 0.9 mEq Table 5.13: Causes of metabolic alkalosis bicarbonate. The recommendation is to replace only half Chloride responsive of the total bicarbonate deficit during the first few hours Gastric fluid loss (e.g. vomiting, nasogastric drainage) of therapy. This amount is given as continuous infusion Volume contraction (e.g. loop or thiazide diuretics, metolazone) over two hours. Rapid correction of acidosis with sodium Congenital chloride diarrhea, villous adenoma bicarbonate can lead to extracellular volume expansion, Cystic fibrosis exacerbating pulmonary edema in patients with cardiac Post-hypercapnia syndrome (mechanically ventilated patients failure. In the latter, the rate of infusion should be slower with chronic lung disease) or sodium bicarbonate replaced by THAM [dose (ml) = Chloride resistant weight (kg) x base deficit] which is infused over 3-6 hr. If Primary aldosteronism (adenoma, hyperplasia) hypernatremia is a concern, sodium bicarbonate may be Renovascular hypertension, renin secreting tumor used as part of the maintenance intravenous solution. Bartter and Gitelman syndromes During correction of acute metabolic acidosis, the effect Apparent mineralocorticoid excess of sodium bicarbonate in lowering serum potassium and Glucocorticoid remediable aldosteronism ionized calcium concentrations must also be considered Congenital adrenal hyperplasia (11 - and 17a-hydroxylase and monitored. Since bicarbonate therapy generates large deficiency) Liddle syndrome amount of CO2, ventilation should increase proportion­ Excess bicarbonate ingestion ately otherwise this might worsen intracellular acidosis. The inability to compensate may be especially important formation of CO2 and water from HC03. Within several in patients with diabetic ketoacidosis who are at risk for hours, elevated levels of HC03- and metabolic alkalosis cerebral edema. In diabetic ketoacidosis, insulin therapy inhibit the respiratory center, resulting in hyp oventilation generally corrects the acidosis. and increased pC02 levels. This mechanism produces In newborns, frequent administration of hypertonic a rise in pC02 of as much as 0.7 to 1 mm Hg for each solutions such as sodium bicarbonate have led to intracranial 1 mEq/1 increase in HC03. hemorrhage resulting from hyperosmolality and resultant fluid shifts from the intracellular space. Children with Clinical Features inherited metabolic abnormalities, poisoning, or renal failure Signs and symptoms observed with metabolic alkalosis may require hemodialysis. usually relate to the specific disease process that caused the Mild to moderate acidosis in renal failure or renal tubular acid-base disorder. Increased neuromuscular excitability acidosis improves on oral alkali therapy, the dose being 0.5 (e.g. from hypocalcemia), sometimes causes tetany or to 2 mEq/kg/day of bicarbonate in 3-4 divided doses. In seizures. Generalized weakness may be noted if the patient cases of acidosis due to volume depletion, the volume deficit also has hypokalemia. Patients who develop metabolic should be corrected. alkalosis from vomiting can have symptoms related to severe volume contraction, with signs of dehydration. Metabolic Alkalosis Although diarrhea typically produces a hyperchloremic Metabolic alkalosis (pH >7.45) is an acid-base disturbance metabolic acidosis, diarrheal stools may rarely contain caused by elevation in the plasma bicarbonate (HC03) significant amounts of chloride, as in the case of congenital concentration in the extracellular fluid that results from a chloride diarrhea. Children with this condition present at net loss of acid, net gain of base or loss of fluid with more birth with watery diarrhea, metabolic alkalosis, and hypo­ chloride than bicarbonate. There are 2 types of metabolic volemia. Weight gain and hypertension may accompany alkalosis classified based on the amount of chloride in the metabolic alkalosis that results from a hyper­ urine, i.e. chloride-responsive or chloride resistant mineralocorticoid state. (Table 5.13). Chloride-responsive metabolic alkalosis shows urine chloride levels of less than 10 mEq/1 and is Treatment characterized by decreased ECF volume and low serum The overall prognosis in patients with metabolic alkalosis chloride levels, such as occurs with vomiting or use of depends on the underlying etiology. Prognosis is good diuretics. This type responds to administration of chloride with prompt treatment and avoidance of hypoxemia. Mild salt (usually as normal saline). Chloride resistant metabolic or moderate metabolic alkalosis or alkalemia rarely alkalosis is characterized by urine chloride levels of more requires correction. For severe metabolic alkalosis, therapy than 20 mEq/l. Primary aldosteronism is an example of should address the underlying disease state, in addition chloride-resistant metabolic alkalosis and this type resists to moderating the alkalemia. The initial target pH and administration of therapy with chloride. bicarbonate level in correcting severe alkalemia are The body compensates for metabolic alkalosis through approximately 7.55 and 40 mEq/1, respectively. buffering of excess bicarbonate and hypoventilation. Intra­ Therapy with diuretics (e.g. furosemide, thiazides) cellular buffering occurs through sodium-hydrogen and should be discontinued. Chloride-responsive metabolic potassium-hydrogen ion exchange, with eventual alkalosis responds to volume resuscitation and chloride  Fluid and Electrolyte Disturbances - repletion. Chloride-resistant metabolic alkalosis may be acidosis can lead to missed therapies and diagnosis. more difficult to control. As with correction of any electrolyte Assisted ventilation is required in many cases. or acid-base imbalance, the goal is to prevent life-threatening complications with the least amount of correction. Respiratory Alkalosis For persistent severe metabolic alkalosis in the setting Respiratory alkalosis occurs in the setting of a primary of fluid overload, wherein saline cannot be given, cautious decrease in pC02 as a consequence of hyperventilation use of HCl or ammonium chloride may be considered. (Table 5.15). In a child this may result from high fever, Acetazolamide may help patients with chloride-resistant sepsis, mild bronchial asthma, central nervous system metabolic alkalosis provided GFR is adequate. Correction disorders or overventilation of an intubated child in of metabolic alkalosis in patients with renal failure may intensive care setting. In acute respiratory alkalosis, require hemodialysis or continuous renal replacement titration is done by intracellular buffers. Renal compen­ therapy with a dialysate that contains high levels of sation begins within several hours and takes several days chloride and low HC03. for the maximal response. Respiratory Acidosis Table 5.15: Causes of respiratory alkalosis Respiratory acidosis occurs when the alveolar ventilation falls or when carbon dioxide production is increased, so Hypoxia and hypoxemia that the arterial partial pressure of carbon dioxide (PaCO2) High altitude or low fraction of inspired oxygen, anemia, is elevated above the normal range (>44 mm Hg) leading hypotension or lung disease to a blood pH lower than 7.35 (Table 5.14). pC02 is directly Pulmonary disorders proportional to carbon dioxide production and inversely Pulmonary edema, embolism, airway obstruction, pneumonia, proportional to alveolar ventilation. The kidneys compen­ intersititial lung disease sate for respiratory acidosis by increasing HC03- reabsor­ Mechanical ventilation (ventilatory rate or tidal volume too ption, a process that begins in 6-12 hr but takes 3-5 days high) for maximal compensation. Extrapulmonary disorders (severe respiratory alkalosis) The kidneys increase excretion of hydrogen ions (pre­ dominantly in the form of ammonium) that increases the Stress, neurologic disease (stroke, infection, trauma, tumor) plasma bicarbonate concentration by approximately Medications: Catecholamines, progesterone, methylxanthines, salicylates, doxapram, nicotine 3.5--4 mEq/1 for every 10 mm Hg increase in CO2. Hyperthermia, hepatic encephalopathy, sepsis, recovery from Clinical Features metabolic acidosis Patients with acute respiratory acidosis frequently demon­ strate air-hunger with retractions and use of accessory Clinical Features muscles. Neurologic findings include anxiety, disorien­ Patients primarily have clinical manifestations of the tation, confusion and lethargy followed by tremors, som­ underlying disorder. Alkalosis, by promoting the binding nolence or coma at higher pC02_ Hypercapnic neurologic of calcium to albumin, can reduce the fraction of ionized changes are reversible with no residual effect. Cardio­ calcium in blood which may manifest as feeling of tingling, vascular findings include tachycardia, bounding arterial paresthesias, dizziness, palpitations, tetany and seizures. pulses and in severe cases hypotension. Therapy is directed towards the causal process. Treatment Suggested Reading The goal of therapy is to correct or compensate for the Carmody JB, Norwood VF. A clinical approach to pediatric acid-base underlying pathologic process. Failure to consider a mixed disorders. Postgrad Med J 2012;88:143-51 Holliday MA, Ray PE, Friedman AL. Fluid therapy for children: facts, fashions and questions. Arch Dis Child 2007;92:546-50 Table 5.14: Causes of respiratory acidosis Lietman SA, Germain-Lee EL, Levine MA. Hypercalcemia in chil­ Decrease in alveolar ventilation dren and adolescents. Curr Opin Pediatr 2010;22:508-15 Depressed central respiratory drive Masilamani K, van der Voort J. The management of acute hyperkale­ Acute paralysis of the respiratory muscles mia in neonates and children. Arch Dis Child 2012;97:376-80 Moritz ML, Ayus JC. Improving intravenous fluid therapy in chil­ Acute or chronic parenchymal lung and airway diseases dren with gastroenteritis. Pediatr Nephrol 2010;25:1383-4 Progressive neuromuscular disease Moritz ML, Ayus JC. New aspects in the pathogenesis, prevention, Worsening scoliosis (restrictive lung disease) and treatment of hyponatremic encephalopathy in children. Pediatr High carbon dioxide production and inability to increase Nephrol 2010; 25:1225-38 minute ventilation Rey C, Los-Arcos M, Hernandez A, Sanchez A, et. al Hypotonic ver­ sus isotonic maintenance fluids in critically ill children: a multicenter Extensive burn injury prospective randomized study. Acta Paediatr 2011;100:1138-43 Malignant hyperthermia Shaw N. A practical approach to hypocalcemia in children. Endocr Fever Dev 2009;16:73-92  Nutrition Vinod K Paul, Rakesh Lodha, Anuja Agarwala Nutrition, also called nourishment, is the provision to cells the enzymes in the gut. Fibers are essential for the normal and organisms of the materials necessary in the form of functioning of the gut, elimination of waste, bile acid food to support life. Our food is made up of essential, binding capacity and for maintaining the growth of normal natural substances called nutrients. There are seven major intestinal microflora. classes of nutrients: carbohydrates, fats, fiber, minerals, proteins, vitamins and water. These nutrients can be grou­ Proteins ped as macronutrients and micronutrients. The macro­ Proteins are the second most abundant substance in the nutrients are needed in large quantities, e.g. carbohydrates, body, after water. They are required for the growth and fats and proteins and are building blocks of the body. The synthesis of tissues in the body; formation of digestive micronutrients, e.g. minerals and vitamins are needed in juices, hormones, plasma proteins, enzymes and hemo­ tiny quantities and are crucial for their role in metabolic globin; as buffers to maintain acid-base equilibrium in the pathways and in enhancing immunity. Micronutrients are body; and as alternate source of energy for the body. discussed in Chapter 7. Amino acids that can be synthesized in the body are called nonessential, while essential amino acids require to be MACRONUTRIENTS supplied in the diet. Carbohydrates Essential amino acids include leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and Carbohydrates are the main source of energy in the Indian valine. Histidine and arginine are essential during infancy diet contributing to 55-60% of total energy intake. because the rate of their synthesis is inadequate for Carbohydrates contribute taste, texture and bulk to the sustaining growth. diet. Lack of carbohydrates (less than 30%) in the diet may produce ketosis, loss of weight and breakdown of proteins. Carbohydrates are divided into simple carbohydrates Protein Quality (monosaccharide and disaccharides such as glucose and Food proteins differ in their nutritional quality depending fructose in fruits, vegetables and honey, sucrose in sugar on their amino acid profile and digestibility. Cereal grains and lactose in milk) and complex carbohydrates (oligo­ are deficient in the essential amino acids like lysine, saccharides and polysaccharides such as starch in cereals, threonine or tryptophan, whereas pulses are rich in lysine millets, pulses and root vegetables). The main source of but are limited in sulfur containing amino acids, mainly energy in the body is glucose derived from starch and methionine. When cereals are taken in combination with sugars present in the diet. Glucose is used as a fuel by the the pulses, the deficiency in one is made good by an excess cells and is converted to glycogen by liver and muscles. in other. Proteins provide 4 kcal energy per gram. Excess carbohydrates are converted to fat. Carbohydrates The following terms are used to describe protein quality: provide 4 kcal of energy per gram. Nitrogen absorbed Fiber True digestibility (TD) = Nitrogen intake x 100 Dietary fibers include polysaccharides such as cellulose, hemicelluloses, pectin, gums, mucilage and lignin. They Nitrogen retained Biological value (BV) x 100 have little nutritional value as they are not digested by Nitrogen absorbed 88 ----------------------------------------N_u_tr-it_i_o_n....- TD Simple lipids Net protein utilization (NPU) = x BV 100 Egg protein has the highest values for BV and NPU and Saturated fatty acids Unsaturated fatty acids I Ghee, butter, coconut oil is therefore taken as the reference protein, and the value of others is expressed as relative to egg (taken as 100%). Generally, animal proteins have a higher BV than the plant Monounsaturated fatty acids Polyunsaturated fatty acids Olive oil, palm oil Corn oil, soya bean oil, proteins. The nutritive value of a mixture of two proteins groundnut oil, mustard oil sunflower oil may be higher than the mean of the two because of mutual complementary effects. Essential fatty acids Requirements The protein allowances shown in Table 6.1 Linoleic acid Linolenic acid are given in terms of the mixed vegetable proteins con­ tained in Indian diets, the NPU of which is assumed to be Fig. 6.1: Classification of fats 65. Nearly 8-12% of the total energy should be provided from protein sources. An intake of 8% proteins may be Fats provide 9 kcal of energy per gram. About 25-30% sufficient for those having a higher content of animal of energy intake should be from fat. However, in proteins or high value proteins in the diet. malnourished children, up to 45% of calories can be provided from fat safely. In India, almost 10-15% of fat is Fats derived from invisible fat; therefore, visible fat intake Fats comprise a diverse group of saponifiable esters of should be restricted to below 20%. Saturated fat should long chain fatty acids. Fats function as structural elements not exceed 7% of the total fat intake; polyunsaturated fat of the cell membranes, are a major source of energy, carry should be restricted to 10% and rest should be derived fat soluble vitamins (A, D, E and K) and are precursors of from monounsaturated fats. A minimum of 3% energy prostaglandins and hormones. should be derived from linoleic and 0.3% from linolenic Fats are present in the diet or the human body in the form acid. of fatty acids (triglycerides), phospholipids and cholesterol. Fatty acids have varying carbon chain length and may be Triglycerides saturated or unsaturated (Fig. 6.1) depending on the predo­ Triglycerides are divided on the basis of chain length into minating fatty acids. The degree of saturation determines medium chain triglycerides (MCT; 6-12 carbon length) or whether the fat is solid or liquid at room temperature. long chain triglycerides (LCT; >12 carbon length). MCTs are Table 6.1: Daily nutrient requirements and recommended dietary allowances for Indian children Age Energy,kcal Protein,g Visible fat,g Calcium,mg Iron,mg Zinc,mg Magnesium, mg 10 g/kg/day, the same treatment should the financial resource to feed the child, is specifically be continued till recovery. If there is a moderate weight gain trained to give appropriate feeding (types, amount, of 5-10 g/kg/day; food intake should be checked and the frequency), lives within easy reach of the hospital, is children should be screened for systemic infection. In case trained to give structured play therapy and is motivated of poor weight gain of 5-10 yr) lymphadenopathy immunodeficiency Recurrent staphylococcal cold abscesses, Any age Coarse facial features, Hype