2009外文讲义3

Etiology Pathogenesis Clinical manifestations Diagnosis Treatment Differential diagnosis diarrhea

Definition Infantile diarrhea is syndrome caused by multi-pathogens & multifactor. Abnormally fluid content in the stool It is easily complicated: disturbances of water electrolyte and acid- base balance It can be classified infectious non-infectious

Etiology Predisposing factors Infectious factors 1. Immature digestive function and rapid growth 2. Poor host defenses 3. Formula feeding 1. Intraintestinal infections 2 . Extraintestinal infections 1. Dietary factors 2. Weather factors Non-infectious factors

morbidity constituent ratio < 1y 38.65% 1- 2y 32.29% Etiology

Low gastric acidity the ability killing pathogens Low activity of digestive enzymes digestive ability Rapid growth nutrient requirements overburden in gastrointestinal tract Predisposing factors Immature digestive function and rapid growth

Poor host defenses IgM resistance to the infection of gram-negative bacilli SIgA resistance to the local infection Newborn infants have not acquired normal enteric flora Prolonged administration of antibiotics a shift in their balance Predisposing factors

Very few microbes are always pathogenic Many microbes are potentially pathogenic Most microbes are never pathogenic Microbes and humans

Formula feeding Have much more opportunities for contamination Some useful agents (C3,C4, lysozyme, lysosome, lactoferrin and some cells ) which breast milk contains are less or have been destroyed in animal milk after heating Predisposing factors Bottle-fed babies are more predisposed to diarrhea

Intraintestinal infections(enteritis) Viruses: (70%) Rotavirus etc. Bacteria: Escherichia coli (E.coli), etc. Fungi: Candida albicans, etc. Protozoa: Entamoeba histolytic, etc. Infectious Factors

The infectious diarrhea dose not include that having legal name such as bacillary dysentery, cholera Diarrhea caused by other infectious agents and unknown pathogens may all be named “ enteritis” and should be defined with the name of the specific pathogen. Such as enteropathogenic E. Coli. enteritis, rotavirus enteritis.

Viruses Bacteria Parasites fungi Rotavirus Salmonella species Giardia lamblia candida albicans Adenovirus Shigella species Cryptosporidium parvum Nowalk agent Escherichia coli Entamoeba histolytica Campylobacter jejunis torovirus, Yersinia enterocolitica Calcivirus Vibrio cholerae Astrovirus Aeromonas hydrophilia Plegiomonas shigelloides Common infectious etiologic agents of acute gastroenteritis

Infection from E. coli - 5 Groups Enteropathogenic E.coli - (EPEC) Enterotoxigenic E. coli - (ETEC) Enteroinvasive E. coli - (EIEC) Enterohemmorhagic E. coli - (EHEC) Enteroadherent aggregative E. coli - (EAEC)

Enterohemorrhagic E. coli O157:H7 Blood stool Abdominal cramps fever Transmission electron micrograph

Extraintestinal infections Otitis media Upper respiratory infection Meningitis Pneumonia Urinary infection Cutaneous infection etc . diarrhea vomiting Infectious Factors

Dietary factors Feeding conditions causing diarrhea among infants: Excess or irregular feeding. Sudden alteration of diet. Feeding starch or fat too early, changing food or weaning suddenly. Allergy to cow’s milk or disaccharidase deficiency. Non-infectious Factors

Weather factors A cool environment increased bowel peristalsis A hot environment digestive juices drink excess milk Non-infectious Factors

Pathogenesis Osmotic diarrhea Secretory diarrhea Exudative diarrhea Abnormal motility It is important to note that more than one mechanism may coexist. For example, in infectious and inflammatory conditions, malabsorption leading to osmotic diarrhea and active secretion can coexist.

Osmotic diarrhea unabsorbable or poorly absorbable solute that exerts an osmotic pressure effect across the intestinal mucosa, resulting in excessive water output. Causes Dietary factors Viral enteritis Pathogenesis

Secretory diarrhea Abnormal ion transport across the intestinal epithelial cells, which results in increased secretion, decreased absorption, or both. A classic example enterotoxigenic E coli (ETEC ). Pathogenesis

Exudative diarrhea Pathogens invade and multiply within intestinal mucosa with inflammatory changes Leak of blood, fluid, pus Impairment of absorption Causes enteroinvasive E.coli(EIEC), Shigella, Salmonella Pathogenesis

Abnormal motility Enhanced motility resulting in rapid gut transit and decreased contact time between luminal contents and absorptive epithelial cells Slow motility may result in bacterial overgrowth Pathogenesis

Bacterial enteritis Enterotoxin Bacteria invasive intestinal mucosa Heat-intolerant Heat-resistant Enterotoxin enterotoxin Adenyl cyclase Guanyl cyclase Congestion, dropsy, ulcer cAMP↑ cGMP↑ Na+ Cl- H 2 O↑ Small intestine juice secrete↑ Stool (blood, mucus shreds, pus) Diarrhea Pathogenesis of Bacterial enteritis

Carbohydrate decomposition & absorption disorder Shedding of epithelial cells on intestine mucous membrane, intestinal villus shortening Intestinal lactic acid ↑ Intestinal Na + & glucose ↑ Disaccharidase activity ↓ Watery diarrhea Na + , glucose coupling transporter disorder Na + , glucose absorption disorder Reabsorbed water-electrolyte ↓ Pathogenesis of Viral Enteritis Virus particles Microvillares epithelial cells on Small intestine mucous membrane Intestines osmotic pressure↑

Pathogenesis of Noninfectious Diarrhea Improper diet Gastric gathered food ， less gastric acid, lower intestinal bacteria up-moving & propagation Decomposition producing Amines ↑ Bacteria & toxicity products short chain organic acid Intestinal osmotic Portal vein system pressure↑ Enterokinesia↑ entering blood circulation Osmotic diarrhea Toxicosis symptom (endogenous infection)

Classified by course Acute infantile diarrhea: <2 weeks Persisting infantile diarrhea: 2 weeks~2 months Chronic infantile diarrhea: >2 months Clinical manifestations

Clinical manifestations GI symptoms Systemic toxic symptoms Disturbances in water, electrolyte, and/or acid-base balances Acute Diarrhea

Gastrointestinal symptoms Other GI symptoms Frequent stools: loose, watery, with pus,mucus, blood ,undigested food Microscopic findings: WBC, RBC, fatty particles Anorexia, nausea, vomiting, abdominal pain and distention Clinical Manifestations Diarrhea

Clinical manifestations Systemic toxic symptoms Abnormal temperature Irritability, lethargy, coma Acute Diarrhea

Water and electrolyte disturbances The most important evidences to distinguish severe diarrhea from mild The usual causes of death in gastroenteritis The correction of them is the fundamental aim of treatment of diarrhea They include: Dehydration Metobolic acidosis Hypokalemia Hypocalcemia and Hypomagnesemia Clinical Manifestations

Characteristics of some specific enteritis Non-infectious diarrhea : The patient mainly presents the gastrointestinal symptoms without or with mild systemic symptoms and water-electrolyte disturbances The stools may contain mucus, froth, or undigested food, but have no pus or blood . Microscopic findings can be negative or only fatty particles.

Infectious diarrhea Often associated with obvious systemic symptoms and water-electrolyte disturbance in addition to gastrointestinal symptoms Characteristics of some specific enteritis

Infectious diarrhea Invasive bacterial enteritis dysentery-like symptoms: frequent stools with mucus, pus and blood. Microscopic findings of stools are a number of leukocytes and erythrocytes. Characteristics of some specific enteritis

Infectious diarrhea Enterotoxigenic bacterial diarrhea or viral diarrhea stools are often frequent, profuse and watery. Dehydration, electrolyte disturbances and acidosis can develop rapidly. No cells or a little leukocytes can be found under microscopy of the stool. Characteristics of some specific enteritis

Candida albicans enteritis occurs predominantly in infants under 2y and with protracted use of antibiotics who have a disturbed enteric bacterial flora. The patient often has also thrush. The stools often have mucus and much froth, candidal filament may be seen under microscope. Characteristics of some specific enteritis Infectious diarrhea

Rotavirus enteritis Pathogen: Human rotavirus (HRV). Predisposing age: 6 - 24 months. Predisposing seasons: autumn and winter. Suddenly onset with low-grade fever and symptoms of common cold, no obvious toxic symptoms. Characteristics of some specific enteritis

Vomiting usually precedes diarrhea. The diarrhea is typically acute in onset and generally watery in character, frequent and in large amount, odorless. It is usually associated with dehydration which is usually isotonic and associated with electrolyte, acid-base disturbance. It is a self-limited disease, the clinical illness generally lasts for 3-8 days Rotavirus enteritis Characteristics of some specific enteritis

Organism Incubation Duration Vomiting Fever Abdominal Pain Rotavirus 1-7 d 3-8 d Yes Low No Adenovirus 8-10 d 5-12 d Delayed Low No Norovirus 1-2 d 2 d Yes No No Astrovirus 1-2 d 4-8 d +/- +/- No Calicivirus 1-4 d 4-8 d Yes +/- No Aeromonas Species None 0-2 wk +/- +/- No Campylobacter Species 2-4 d 5-7 d No Yes Yes Entamoeba species 5-7 d 1-2+ wk No Yes No Organisms and Frequency of Symptoms

Organism Incubation Duration Vomiting Fever Abdominal Pain Enterohemorrhagic E coli 1-8 d 3-6 d No +/- Yes Enterotoxigenic E coli 1-3 d 3-5 d Yes Low Yes Salmonella Species 0-3 d 2-7 d Yes Yes Yes Shigella Species 0-2 d 2-5 d No High Yes Vibrio species 0-1 d 5-7 d Yes No Yes Giardia Species 2 wk 1+wk No No Yes Campylobacter Species 2-4 d 5-7 d No Yes Yes Cryptosporidium species 5-21 d Months No Low Yes Organisms and Frequency of Symptoms

Dehydration Clinical features of dehydration Degrees of dehydration Types of dehydration Clinical Manifestations Water and electrolyte disturbances

Higher metabolic rates Increased body surface area to mass index Higher body water contents (water comprises approximately 70% of body weight in infants, 65% in children, 60% in adults) Young pediatric patients tend to be more susceptible to fluid losses a quick turnover of fluids and solute

Normal routes of fluid excretion in infants and children. Lungs Skin Urine & feces insensible water losses

Sudden weight loss Changes in activity level (restless, lassitude, lethargy, coma) Thirst and dry mouth Sunken eye sockets and tearless Sunken anterior fontanel ( infant) Dry skin and poor skin turgor Decreased urination (Oliguria) Severe cases: poor peripheral circulation ( prolonged capillary refill time) or even shock Dehydration

Clinical features of dehydration in an infant prolonged

Degrees According to weight loss: Dehydration 100~120 50~100 50 Volume deficit (ml/kg) >10% 5%~10% <5% Weight loss (% of BW) severe moderate mild Extent

Degrees According to the severity of the symptoms and signs The key point to distinguish severe cases from mild and moderate ones is poor peripheral circulation and even shock. Dehydration

Dehydration 5-10% Slight sunken

Types of dehydration Hypertonic Isotonic Hypotonic The type is defined according to the change of serum osmolality (serum Na+ concentration) Dehydration

Isotonic dehydration The commonest type of dehydration in acute infantile diarrhea(acute dehydration) The volume of ECF , but no shift of water between ECF and ICF. Loss of equal amounts of water and sodium with normal serum Na concentration (130~150mmol/L). Types of dehydration Definition:

Hypotonic dehydration A shift of water from ECF to ICF 1. More obvious signs of dehydration and a greater degree of shock per unit of water loss. 2. The increase in the volume of ICF leads to an increase in brain volume, sometimes resulting in convulsions. More common in poorly nourished infants or with prolonged diarrhea in developing countries . Loss of more sodium than water with low serum Na concentration (<130mmol/L) Types of dehydration Definition:

Hypertonic dehydration Loss of more water than sodium with high serum Na concentration (>150mmol/L) 1. Less obvious signs of dehydration 2. Particularly dangerous : Water is drawn out of the brain and cerebral shrinkage within a rigid skull may lead to multiple, small cerebral haemorrhages and convulsions. A shift of water from ICF to ECF The least common, usually results from high insensible water losses or from profuse, low-sodium diarrhea Types of dehydration Definition:

Hypertonic dehydration Isotonic dehydration Hypotonic dehydration humour distribute Interstitial fluid plasma ICF

Property of dehydration ICF: severely decrease, Milder dehydrant sign than the other two kinds >150 mmol / L High grade fever, Infection Hypertonic ECF: severely decrease, Easily shock ， Severer dehydrant sign than the other two kinds <130 mmol / L Chronic gastrointestinal fluid lose Hypotonic ECF: decrease, Osmotic pressure (intracellular = extracellular) Dehydrant volume accord with dehydrant physical sign 130 ～ 150 mmol / L Acute gastrointe-stinal fluid lose Isotonic Pathophysiology & clinical characteristic Serum sodium Pathogeny Type of dehydration

Metabolic acidosis Degrees of acidosis Clinical manifestations

Degrees According to the serum HCO 3 - or CO 2 CP Metabolic acidosis <20 <9 Severe acidosis 20-30 9-13 Moderate cidosis 30-40 13-18 Mild acidosis 40-60 18-27 Normal CO 2 CP(vol%) HCO 3 - ( mEq/L)

Clinical manifestations Lassitude, lethargy, coma or irritability Deep, rapid respiration and cool expiratory air The expiratory air smells like ‘acetone’ Cherry lips Nausea, vomiting Metabolic acidosis

Hypokalemia Definition Features of the body potassium before and after rehydration Clinical manifestations Hypokalemia is a condition of below normal levels of potassium in the blood serum(<3.5 mmol/L) .

Heart symptoms Renal symptoms Neuromuscular symptoms Hypokalemia

Clinical manifestations tachycardia, arrhythmia, dull heart sounds ECG T wave depression, the appearance of a U wave, S-T segments depression, prolonged Q-T intervals. Heart symptoms: Increased myocardial irritability: Hypokalemia

Clinical manifestations Hypokalemia Renal symptoms: Lassitude, weakness, hypotonia, diminished reflexes and even paralysis Abdominal distention with diminished or absent peristalsis Hypokalemic and hypochloremic alkalosis Neuromuscular symptoms Depressed irritability: Polyuria Impaired concentrating ability

Serum K usually remains normal prior to rehydration 1. hemoconcentration 2. During acidosis potassium moves from ICF into ECF 3. Oliguria reduces the excretion of potassium Along with rehydration serum K will gradually fall, because: 1. Hemodilution 2. Acidosis is being corrected, potassium returns from ECF to ICF 3. Potassium excretion is increased along with urine discharge 4. Synthesis of glycogen with infused glucose needs potassium 5. Ongoing loss of potassium due to diarrhea Features of the body K before and after rehydration In the presence of a body potassium deficit

Hypocalcemia and Hypomagnesemia Definition Features before and after rehydration Manifestations : Tetany and convulsion If the tetany or convulsion is not relieved after the patient has been given calcium, hypomagnesemia should be considered. A condition of below normal levels of Ca (<1.75 mmol ) or Mg (<0.6 mmol ) in the blood serum

Features before and after rehydration

Diagnosis Clinical diagnosis history (including feeding history and epidemical data), manifestations, physical examination and routine examination of stool. Dehydration (degree and type), electrolyte disturbances and acidosis should be assessed for moderate and severe cases. Ancillary data : WBC counts of peripheral blood to assess risk of bacterial infection Serum electrolyte and blood gas analysis Etiological diagnosis for enteritis depends on stool bacteria culture or virus identification which are not always available.

Differential Diagnosis Physiologic diarrhea It occurs in infants apparently fatty, younger than six months, usually breast feeding. Accompanied by eczema. Besides diarrhea the infants have no other symptoms and have good appetite and normal weight gain. After solid foods (supplemental food) were added the stools turn to normal

Bacillary dysentery Epidemic data (contact history) Stool bacteria culture. Differential Diagnosis

Acute necrotizing enterocolitis Severe systemic toxic symptoms Obvious bloody diarrhea Differential Diagnosis

Treatment Principles regulating and continue feeding correcting water and electrolyte disturbances controlling intestinal and extraintestinal infection good care and symptomatic treatment

Treatment Fasting severe vomiting Regulating and limiting the diet Antibiotic : bacterial infection Microecological drug : lactobacilli GI tract mucosa protector : smecta Drug therapy Fluid therapy Mainstay of treatment Dietary therapy

Fluid therapy Purpose : Correction of dehydration, electrolyte and acid-base imbalances Common solutions used in fluid therapy Oral fluid therapy Intravenous fluid therapy

Common solutions Non-electrolyte solution Electrolyte solutions Mixed solution Oral rehydration salt(ORS) Fluid therapy

Non-electrolyte solution 5%(isosmotic ) 10% (hyperosmotic ) Because the glucose is used for energy supply after it enters the body, the solutions are known as no tonic solutions only used in providing water and calories. Fluid therapy Glucose solution (GS)

Tonicity or effective osmolality is the ability of a solution to cause water movement . solution osmotic pressure plasma osmotic pressure solution osmotic pressure = %concentration×10×1000×each molecule dissociable ion molecule weight It’s a ratio =

0.9%NaCl osmotic pressure = 0.9×10×1000×2 58.5 Tonicity = 308 ｍＯｓｍ / Ｌ 300 ｍＯｓｍ / Ｌ = 308 ｍＯｓｍ / Ｌ solution osmotic pressure = %concentration×10×1000×each molecule dissociable ion molecule weight solution osmotic pressure plasma osmotic pressure = =1

tonicity include isotonic : An extracellular solution that has effectively the same concentration of solution as that found within a cell hypertonic : A hypertonic solution has higher solution concentrations on the outside. in a net movement of water out of cells. hypotonic : A hypotonic (hypoosmotic) solution has a lower concentration on the outside , in a net movement of water into cells.

Fluid therapy Electrolyte solutions Sodium chloride solution (NaCl) Isotonic (0.9%, Normal saline, NS): Replenish volume. Maintain plasma osmolality Hypertonic(3%) Correct hyponatremia Sodium bicarbonate (SB)(NaHCO 3 ) Isotonic(1.4%) Maintain plasma osmolality, correct acidosis Hypertonic(5% , 3.6 tonic) Correct acidosis Potassium chloride (KCl) Isotonic(1.2%) Hypertonic(10% ,8.9 tonic ) Replenish K+

Mixed solution Components of mixed solution solution component ratio NS 5%/10%GS 1.4%SB 2:1 isotonic sol 2 1 1:1 sol (1/2tonicity) 1 1 2:3:1 sol (1/2tonicity) 2 3 1 4:3:2 sol (2/3tonicity) 4 3 2 1:2 sol (1/3tonicity) 1 2 1:4 sol (1/5tonicity) 1 4 Prepared with different portions of various isotonic electrolyte solutions and glucose solution.

Oral fluid therapy Mild or moderate dehydration. No severe vomiting or abdominal distention Indications ORS may be used with unlimited water intake. The fluid is best given in small amounts frequently . Fluid therapy

Ingredient amount (grams) NaCl 3.5 NaHCO 3 2.5 KCl 1.5 Glucose 20 Water 1000ml Oral rehydration salt (ORS) It has been advocated by the WHO Formula of rehydration salt: 2/3 tonicity and the potassium concentration is 0.15%

40℃ warm water or cooled boiled water Oral rehydration salt (ORS)

Indications Principles Methods The first day The second day Fluid therapy Intravenous fluid therapy

Indications Moderate or severe dehydration The illness is not relieved by oral fluid therapy or complicated with severe vomiting. Intravenous fluid therapy

Principles Correcting volume and electrolyte deficits and correcting acid-base imbalances Supplying maintenance requirements Replenishing ongoing abnormal losses Intravenous fluid therapy

The therapy for the first day Volume supplement Correcting acidosis Replacement of potassium Replacement of calcium and magnesium Intravenous fluid therapy

Volume supplement To determine the amount of fluid to be infused To determine the kind of fluid to be infused To determine the infusion rate (speed) Three “determination”

The amount of fluid 60-80 ml/kg /day Maintenance requirements 10-30ml/kg/day Ongoing abnormal losses 100-120 50-100 50 Preexisting losses (ml/kg) 150-180 120-150 90-120 Total amount (ml/kg) Severe Moderate Mild Degrees of dehydration

losing continuing 1/2 ～ 1/3 tonic Sodic solution physiological need 1/3 ～ 1/5 tonic Sodic solution The Quality of fluid 1/3 ～ 1 / 5 Tonic Sodic solution Hypertonic dehydration 2:3:1 Isotonic dehydration 4:3:2 Hypotonic dehydration Cumulated losing volume Dehydrant category

Shock volume expansion Volume Solution Speed 20ml/kg 2:1 30 ～ 60min 1.4%NaHCO 3 Total volume ≤ 300ml Speed

Speed 5ml / kg / h 8 ～ 10ml / kg / h 12 ～ 16h 8 ～ 12h 24h Keep transfusing period （ physiological need, losing continuing ） Cumulated losing volume Total volume

Correcting acidosis Mild acidosis is easily corrected with volume restoration As the fluid infused contains certain amounts of alkaline solutions and increased renal perfusion permits excretion of excess H + ions in the urine For severe acidosis 1.4%SB (20ml/kg) may be used instead of 2:1 solution for volume expanding therapy. 1ml/kg of 5%SB, can elevate 1mEq/L of HCO 3 - Usually give half of the amount calculated and further regulation is based on further HCO 3 - or blood gas analysis. Intravenous fluid therapy

Replacement of potassium The amount of potassium to be replaced Mild hypokalemia: 200-300mg/kg/day or 3- 4mEq/kg/d (KCl) Severe hypokalemia: 300-450 mg/kg/day or 4-6 mEq/kg/d Some key points should be paid attention to: Intravenous fluid therapy

key points about K + replacement Potassium should not be administered unless the patient has passed urine during 6 hours before admission The concentration of KCl in the infusion should be 0.15-0.3%, not to exceed 0.3% ( 27 mEq/L or 0.2% of KCl is the best) The solution containing potassium can not be injected intravenously quickly. The duration of infusion should be beyond 6-8 hrs. In order to balance the amount of potassium between ECF and ICF, potassium losses are usually replaced over a 4-6 day period

Replacement of calcium and magnesium If patients show the symptoms of hypocalcemia (tetany or convulsion) calcium should be administered 10% Calcium gluconate 10ml + 10% glucose 10ml intravenous injection slowly If the symptoms are not improved, magnesium should be given. Intravenous fluid therapy

The therapy for the second day The fluid therapy on the second day is mainly composed of replacement of ongoing normal and abnormal losses with 1/2 or 1/3 sodium-containing solutions. The volumes of ongoing abnormal losses are dependent on the amount of diarrhea stools. Correcting acidosis and hypokalemia if necessary Intravenous fluid therapy

If we could prevent rotavirus: We would save the lives of 1,400 children a day. We would save countries’ precious human and financial resources. We would make a difference. 2006, USA. oral, vaccine for use in preventing rotavirus gastroenteritis in infants. This vaccine gives health care providers an important new tool that can effectively prevent an illness that affects almost all children within the first few years of life vaccine

Definition: Dehydration Isotonic dehydration Hypotonic dehydration Hypertonic dehydration Hypokalemia Key Points

Etiology of infantile diarrhea To evaluate the severity of dehydration caused by infantile diarrhea, you should pay attention to some signs For fluid therapy, the commonly used non-electrolyte solution and the electrolyte solutions 2:1 isotonic solution ,2:3:1 solution component and usage key points about K + replacement the main distinction between severe and mild infantile diarrhea Key Points

How to expand the plasma volume Which sodium-containing solution (tonicity) is choice in different types of dehydration Clinical signs and symptoms of moderate dehydration The total amount of fluid to be supplemented in different degrees of dehydration The treatment principle of infantile diarrhea Features of the body K before and after rehydration, why? The features of physiologic diarrhea Key Points

2009外文讲义3

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2009外文讲义3