Pathophysiology of Body Fluids and Fluid Therapy

Total Body Water, Intracellular fluid and extracellular fluid as a percentage of body weigth and a function of age

 Compartments of total body water, expressed as a percentage of body weight, in an older child or adult

 The Concentration of the major cations and anions in the intracellular space and the plasma, expressed in mEq/L.

Causes of Hypernatremia
Excessive Sodium
Improperly mixed Formula Excess sodium bicarbonate Ingestion of seawater or sodium chloride intentional salt poisoning (child abuse of Munchhausen syndrome by proxy) Intravenous hypertonic saline Hyperaldosteronism

Water Deficit
Nephrogenic Diabetes Insipidus Acquired X-Linked (MIM 304800) Autosomal Recessive (MIM 222000) Central Diabetes Insipidus Acquired Autosomal Dominant (MIM 125700) Increased Insensible Losses Premature Infants Radiant Warners Phototherapy Inadequate Intake Ineffective breast-feeding Child negfect of abuse Adipsia (Lack of thirst)

Water And Sodium Deficits

Gastrointestinal Losses Diarrhea Emesis/Nasogastric suction Osmotic Cathartics (e.g.lactulose) Cutaneous Losses Burns Excessive sweating Renal Losses Osmotic Diuretic (e.g.mannitol) Diabetes Melitus Chronic kidney disease (e.g.dysplasia and obstructive uropathy ) Polyuric phase of acute tubular necrosis Post obstructive diuresis

 Mechanism of brain edema during correction of hypernatremia

Pseudohyponatremia Hyperosmolality

Hyperglycemia Mannitol

Hypovolemic Hyponatremia
Extrarenal Losses
Gastrointestinal (Emesis,Diarrhea ) Skin ( Sweating or Burn ) Third space Losses

Renal Losses
Thiazide or loop diuretic Osmotic diuresis Post obstructive diuresis Polyuric phase of ATN Juvenile nephronophthisis ( MIM 256100/602088/266900/604387) Autosomal recessive polycistic kidney kidney disease (MIM 263200 ) Tubulointerstitial nephritis Obstructive uropathy Cerebralsalt wasting Proximal (Type II) RTA (MIM 604278 ) Lack of aldosterone effect (high serum potassium) Absent aldosterone(e.g.21-hydroxylase deficiency [MIM 201910] ) Pseudohypoaldosteronism type I (MIM 264530 and 177735 ) Urinary Tract obstruction and/or urinary tract infection

Euvolemic hyponatremia
Syndrome of inappropriate antidiuretic hormone Desmopressin acetate Glucocorticoid deficiency Hypothyroidism Water Intoxication Istrogenic (i.e.excess hypotonic intravenous fluids ) Swimming lesson Tap water enema child abuse Psychogenic polydipsia Diluted formula Beer potomania

Hypervolemic hyponatremia
Congestive heart failure Cirrhosis Nephrotic Syndrome Renal Failure Capillary leakdue to sepsis Hypoalbuminemia due to gastrointestinal disease

CAUSES of HYPERKALEMIA
Spurious Laboratory Value
Hemolysis Tissue Ischemia during blood drawing Thrombocytosis Leukocytosis

Increased Intake
Intravenous or oral Blood transfusions

 Transcellular Shifts
Acidemia Rhabdomyolysis Tumor lysis syndrome Tissue necrosis Hemolysis/hematomas/GI bleeding Succinylcholine Digitalis Intoxication Fluoride Intoxication Beta-adrenergic blockers Exercise Hyperosmolality Insulin deficiency Malignant hyperthermia (MIM 145600) Hyperkalemic periodic paralysis (MIM 170500)

Decreased Excretion
Renal Failure
Primary Adrenal disease
Acquired Addison disease 21-hydroxylase deficiency (MIM 201910) 3-hydroxysteroid dehydrogenase deficiency (MIM 201810) Lipoid kongenital adrenal hyperplasia (MIM 201710 ) Adrenal hypoplasia congenita (MIM 300200) Aldosterone syntase deficiency (MIM 203400) Adrenoleukodystrophy (MIM 300100)

Hyporeninemic hypoaldosteronism
Urinary tract obstruction Sickle cell disease (MIM 603903) Kidney Transplant Lupus Nephritis

Renal Tubular Disease

Pseudohypoaldosteronism type I (MIM 264350 and 177735) Pseudohypoaldosterone type II (MIM 145260 ) Urinary tract obstruction Sickie cell disease Kideney Transplant

 Medications
Angiotensin converting enzyme inhibitors Angiotensin II blockers Potassium sparing diuretics Cyclosporin Nonsteroidal anti inflammatories Trimethoprim

Causes of Hypokalemia
Spurious
High white blood cell count

Transcellular Shifts
Alkalemia Insulin Adrenergic agonist Drugs/toxins (theophyline barium, toluene) Hypokalemic periodic paralysis (MIM*170400)

Decreased Intake Extrarenal Losses

Diarrhea Laxative abuse Sweating

Renal Losses
With Metabolic Acidosis Distal renal tubular acidosis (RTA) (MIM 179800/602722) Proximal RTA (MIM 6042781) Ureterosigmoidostomy Diabetic Ketoacidosis
Without specific acid based disturbanced Tubular toxins amphotericin, cisplatin, aminoglycosides Interstitial Nephritis Diuretic phase of acute tubular necrosis Postobstructive diuresis Hypomagnesemia High urine anions (e.g. penicillin or penicillin derivative)

 With metabolic Alkalosis

Low urine chloride Emesis nasogastricsuction Chloride losing diarrhea (MIM 214700) Cystic fibrosis (MIM 219700) Low chloride formula Posthypercapnia Previous loop or thiazide diuretic use High urine chloride and normal blood pressure Gitelman syndrome (MIM 263800) Bartter syndrome (MIM 602023) Loop and Thiazide diuretic

High urine chloride and high blood presurre

Adrenal adenoma or hyperplasia Glucocorticoid remedial aldosteronism (MIM 103900) Renovascular Disease Renin secreting tumor 17 hydroxylase deficiency ( MIM 202110) 11 hydroxylase deficiency (MIM 202010) Cushing Syndrome 11 hydroxysteroid dehydrogenase deficiency (MIM 218030) Licorice ingestion Liddle syndrome (MIM 177200)

Causes of Hypocalcemia
Specific Causes In The Neonate
Early neonatal hypocalcemia Late neonatal hypocalcemia Maternal hypercalcemia

Hypoparathyroidism
DiGeorge syndrome (MIM* 188400) X Linked hypoparathyroidsm (MIM 307700) Parathyroid hormone (PTH) gene mutations (MIM 168450) Calcium sensing receptor mutation (MIM 601199) Autosomal recessive hypoparathyroidsm with dysmorphic features (MIM 241410) HDR (or Barakat ) syndrome ( MIM 146255 ) Autoimmuno polyglandular syndrome type I (MIM 240300) Kearns sayre syndrome (MIM 530000 ) Hemochromatosis Wilson disease ( MIM 277900 ) Postsurgical hypoparathyroidism Radioactive iodine ablation of the thyroid gland Hypomagnesemia

Lack of Response to PTH

Pseudohypoparathyroidism type IA ( MIM 103580 ) Pseudohypoparathyroidism type IB ( MIM 603233 ) Pseudohypoparathyroidism type II Hypomagnesemia

Vitamin D Deficiency
Poor Intake Lack of Sunligth Malabsorption Increase Metabolism (e.g.,anticonvulsants) Failure to form 25 hydroxyvitamin D in the Liver Vitamin D dependent rickets type 1 ( MIM 264700 ) Vitamin D dependent rickets type 2 ( MIM 277420 ) Renal Insufficiency

Redistribution of Plasma Calcium

Hyperphosphatemia Rhabdomyolysis Tumor Lysis syndrome Blood Transfusions Hungry bone Syndrome Acute Pancreatitis Osteopetrosis, Infantile ( MIM 259700 )

Inadequate calcium Intake

Calcium Poor diet or total parenteral nutrition Dietary calcium chelator Malabsorption

Unknown
Septic Shock Critical illness

Causes Of Hypercalcemia
Excess Parathyroid Hormone
Primary Hyperparathyroidsm
Sporadic Adenoma Familial Isolated Hyperparathyroidism ( MIM *145000 ) Multiple Endocrine Neoplasia type I ( MIM 131100 ) Multiple Endocrine Neoplasia type II ( MIM 171400 ) Hyperparathyroidism Jaw Tumor Syndrome ( MIM 145001 ) Calcium - Sensing receptor mutation ( MIM 239200 )

Transient Secondary Neonatal Hyperparathyroidism Tertiary Hyperparathyroidism

Excess Vitamin D
Hypervitaminosis D Subcutaneous fat Necrosis Sarcoidosis Granulomatous disease (e.g.,tuberculosis and Fungal Infections ) Lymphomas

 Excess Calcium Intake

Calcium Supplements Latrogenic (e.g., total parenteral nutrition )

Excess Renal Reabsorption of Calcium

Familial Benign hypocalciuric hypercalcemia ( MIM 145980 ) Thiazide Diuretic

Release From Bone

Thyrotoxicosis Hypervitaminosis A Malignancy Associated Ectopic parathyroid hormone ( PTH ) PTH related peptide Bone Metatasis Other Factors Immobilization Renal Osteodystrophy Low turnover disease Aluminum Deposition

 Miscellaneous
Williams Syndrome ( MIM 194050 ) Hypophosphatemia Pheochromocytoma Adrenal Insufficiency Recovery Phase of rhabdomyolisis Jansen metaphyseal chondrodysplasia ( MIM 156400 ) Hypophosphatasia ( MIM 241500 )

Clinical Manifestations of Hypercalcemia

Gastrointestinal
Nausea and Vomiting Poor Feeding Failure to Thrive Constipation Abdominal Pain Pancreatitis Peptic ulcer

Cardiac
Hypertension Decreased QT Interval Arrhythmias

Central Nervous System

Lethargy Hypotonia Psychiatric disturbances Coma

Kidney
Polyuria and Dehydration Hypernatremia Renal Failure Nephrolithiasis

Causes of Hypomagnesemia
Gastrointestinal Disorders
Diarrhea Nasogastric Suction or emesis Inflammatory bowel disease Celiac disease Intestinal hymphangiectasia Small bowel resection or bypass Pancreatitis Protein calorie malnutrition Primary Intestinal hypomagnesemia with secondary hypocalcemia ( MIM * 602014 )

Renal Disorders
Medications: amphotericin, cisplatin, cyclosporin, loop diuretics, mannitol, pentamidine, aminoglycosides, thiazide diuretic Diabetes Acute tubular necrosis ( recovery phase ) Postobstruvtive nephropathy Chronic kidney diseases: Interstitial nephritis, glomerulonephritis, postrenal transplant Hypercalcemia Intravenous fluids Primary aldosteronism Genetic diseases Gitelman Syndrome ( MIM 263800 ) Bartter Syndrome ( MIM 602023 ) Familial hypomagnesemia with hypercalciura and Nephrocalcinosis ( MIM 603959 ) Autosomal recessive renal magnesium wasting ( MIM 248250 ) Autosomal dominant renal magnesium wasting ( MIM 154020 ) Autosomal dominant hypoparathyroidism ( MIM 601198/601199 ) mitochondrial disorders

 Miscellaneous Causes
Poor Intake Hungry Bone Syndrome Insulin Administration Pancreatitis Intrauterine growth retardation Infants of Diabetic mothers Exchange Tranfusion

Causes of Hypophosphatemia
Transcellular Shifts
Glucose Infusion Insulin Refeeding Total Parenteral Nutrition Respiratory Alkalosis Tumor growth Bone marrow transplantation Hungry bone syndrome

Decreased Intake
Nutrional Premature Infants Low Phosphorous formula Antacids and other phosphate binder

 Renal Losses
Hyperparathyroidism Parathyroid hormone related peptide X Linked hypophosphatemic rickets ( MIM*307800 ) Tumor Induced osteomalacia Autosomal dominant hypophosphatemic rickets (MIM 193100 ) Fanconi syndrome Dent disease ( MIM 300009 ) Hypophosphatemic rickets with hypercalciura ( MIM 241530 ) Volume expansion and intravenous fluids Metabolic acidosis Diuretic Glycosuria Glucocorticoids Kidney Tranplantation

 Multifactorial
Vitamin D deficiency Vitamin D dependent rickets type 1 ( MIM 264700 ) Vitamin D dependent rickets type 2 ( MIM 277440 ) Alcoholism Sepsis Dialysis

Causes of Hyperphosphatemia
Transcellular Shifts
Tumor Lysis Syndrome Rhabdomyolysis Acute hemolysis Diabetic Ketoacidosis and lactic acidosis

Increase Intake
Enemas and laxatives Cows Milk in infants Treatment of hypophosphatemia Vitamin D intoxication

 Decreased Excretion
Renal Failure Hypoparathyroidism Acromegaly Hyperthyroidism Tumoral calcinosis with hyperphosphatemia ( MIM*211900 )