Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Infantile Diarrhea SUN Mei Pediatric Dept. 2nd Clinical College, China Medical University Introduction 1. Definition: Infantile diarrhea is one of the most common diseases in infants and toddlers. It is not a definitely disease but a syndrome caused by infectious and non-infectious factors. Clinical manifestations are mainly diarrhea and vomiting, in severe cases it usually associated with dehydration and electrolyte and acid-base disturbances. Major causes of death among children under five in developing countries, 2002 18% 25% Deaths associated with malnutrition 54% 15% 10% 23% 4% 5% Acute respiratory infection Diarrhea Malaria Measles HIV/AIDS Perinatal Other Sources: The world health report 2003, WHO,Geneva. 2.Nomenclature: Infectious Noninfectious. The infectious diarrhea dose not include that having legal name such as bacillary dysentery, cholera and so on. 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. 3. Predisposing age Peak incidence occurs in infants under two to three years of age. Especially under one year, which account for about half of the patients. 4. Prevalent seasons Bacterial enteritis is most prevalent in summer. Viral enteritis in autumn and winter months but they may be occur all year round. Noninfectious diarrhea may occur at any season. Predisposing factors 1. Immature digestive function Low gastric acidity: Normally in adults and adolescents the majority of ingested bacterial pathogens will be killed at the acid environment of stomach (pH 1.5-2.0, <4) and can not get into the intestine. but in infants the low gastric acidity decrease the ability of killing the ingested bacterial. Low activity of digestive enzymes: Enzymes such as amylase can not suit the changes of food in quantity and quality. 2. The rapid growth. The body weight of one year old children is 3 times of birth weight. The nutrient requirements are relatively great, the gastrointestinal tract is usually overburdened and commonly encounter stress. 3. Poor immune function (host defenses) Immunoglobulins especially the level of IgM and secretory IgA from gastrointestinal mucosa are very low. The SlgA could resist the local infection of mucosa and IgM could resist infection of gram-negative bacilli. 4. Disturbed enteric bacterial flora: Normal bacterial flora is highly effective in resisting colonization by potentially pathogenic invaders. The newborn infants have not acquired a normal enteric flora. In infants, the GI normal flora can easy lose or shift in their balance by antibiotics or other factors, which may increase the infants’ susceptibility to enteric infections. 5. Formula feeding: Bottle-fed infant has much more opportunities of contamination; Breast milk contains many factors such as SIgA, complement C3, C4, lysozyme, lysosome, lectoferrin and some cells, these factors are less in animal milk or have been destroyed after boiling. Etiology Infectious factors 1. Intestinal infection Viruses. – Rotavirus is the most common cause of infantile diarrhea especially in autumn and winter. – Norwalk virus is more responsible for diarrhea among older children and adults. – Others such as calicivirus (杯状病毒),enteric adenovirus, astrovirus, corona-like viruses, small round viruses, ECHO, Coxsackie, CMV. Etiology Bacteria Escherichia coli (E. coli) Enteropathogenic E. coli EPEC Enterotoxigenic E. coli ETEC Enteroinvasive E. coli EIEC Enterohemorrhagic E. coli EHEC Enteroadherent-aggregative E. coli EAEC Campylobacter jejuni, Yersinia enterocolitica. Other bacteria: such as staphylococcus aureus, pseudomonas aeruginosa, proteus, Klebsiella, Salmonella typhymurium and citrobacter. Etiology Fungi: especially Candida albicans Protracted use of broad-spectrum antibiotics may alter the normal enteric flora, that may allow the emergence of resistant organisms such as staphylococcus aureus or Candida albicans, especially in debilitated children and those with immunologic deficiency. Protozoa Entamoeba histolytic, Giardia Lamblia Balantidium coli. Etiology 2. Extraintestinal infections Otitis media, upper respiratory infection, meningitis, pneumonia, urinary infection, cutaneous infection or other acute infectious diseases may associate with diarrhea and vomiting. Extragastrointestinal infections cause a temporary upset of gastrointestinal function (toxin, fever). Pathogens infect intestine directly. Local irritation of the rectum (bladder infection). Etiology Antibiotic-associated diarrhea, AAD: Some antibiotics decrease carbohydrate transport and intestinal lactase levels. Eradication of normal gut flora and overgrowth of other organisms may cause diarrhea. Etiology Noninfectious factors Dietary factor : 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. Weather factor Cool increased bowel peristalsis Hot secretion of digestive juice may decrease thirsty excess drinking over burdened GI tract. Pathogenesis Each kind of diarrhea has different pathogenesis, such as: “secretary” “effusive” “osmotic” “abnormal GI peristalsis” Rotavirus invade the mucosa of small intestine ↓ Mucosa shows patchy inflammation, microvilli are irregular, swollen and shortened ↓ Epithelial cells are swollen, microvilli are damaged Glucose-coupled Decreased activity of The total absorptive sodium transport disaccharidase area decrease decreased ↓ ↓ Lactose can not be watery stools digested and absorbed ↓ Organic acid increased ↓ Osmolarity is increased in IT Figure 1. Pathogenesis of rotaviral enteritis Ingested ETEC (ID=108 ) ↓ adhere to and colonize in upper intestinal mucosa via colonization factors (CF) and multiply ↓ Produce enterotoxins (ST and/or LT) ↓ ↓ heat-stable enterotoxin heat-labile enterotoxin ↓ bind to receptors and activate ↓ Guanyl cyclase Adenyl cyclase ↓ ↓ GTP → cGMP↑ cAMP↑← ATP ↓ ↓ →→ Promote ←← secretion of sodium, chloride, water ↓↓ watery diarrhea Figure 2. Pathogenesis of ETEC enteritis Invasive pathogens ↓ invade and multiply within intestinal mucosa ↓ inflammatory changes (congestion, swollen, inflammatory cells infiltration, effusion and ulcer) ↓ water and electrolyte are not absorbed entirely ↓ diarrhea / \ WBC,RBC increase severe general in stools toxic symptoms Figure 3. Pathogenesis of invasive enteritis Feeding fault (overfeeding, unsuitable nutrients) ↓immature digestive function ↓ overburdened GI tract Disturbances of digestive function ↓ Nutrients can not be digested and absorbed properly ↓ Accumulated in upper intestinal tract. Acidity of contents decrease ↓ Bacteria resided in lower IT immigrate into and multiply in upper IT ↓ (endogenous infection) Nutrients are resolved by bacteria ↓ ↓ Fermentative process putrid process ↓ ↓ Organic acids are increased toxic products(amines etc.) (Lactic and acetic acid) ↓ ↓ ↓ liver Hyperosmolarity irritate ↓ ↓ ↓ Blood stream hyperperistalsis of intestinal wall ↓ ↓ General toxic symptoms Diarrhea Figure 4. Pathogenesis of dietary diarrhea Clinical manifestations Classification by the course of diarrhea Acute diarrhea: continuous course < two weeks Prolonged diarrhea: continuous course varies between 2 weeks ~ 2 months Chronic diarrhea: > 2 months. According to severity of diarrhea it may be divided into 2 types: Mild diarrhea: caused by dietary factors or extragastrointestinal infections. Gastrointestinal symptoms: The stools become frequent but usually no more than ten times a day, gruel-like or watery, yellow or greenish yellow in color, smell sour, Vomiting is less common and abdominal pain is mild. Systemic symptoms: There is no obvious systemic symptoms. Infants may be restless or irritable, temperature is normal or slight high. There is no dehydration, electrolyte and acidbase disturbances. Severe diarrhea: caused by intestinal infections. Gastrointestinal symptoms: The stools become more frequent, >10 times daily, watery in consistency, yellow or greenish yellow, sometimes with mucus, pus and blood. Vomiting is severe even blood in vomitus. Other symptoms include: anorexia, nausea, abdominal pain and abdominal distention. Systemic symptoms: Obvious systemic toxic symptoms. Infants may be very irritable, lethargy even coma. The temperature may be high or low. Water and electrolyte disturbances: usually present moderate even severe dehydration, acidosis and electrolyte disturbances. Dehydration: Excessive Loss of Water and Electrolytes Due to Diarrhea and Vomiting. Some signs are usually used as criteria. Dryness of lips, skin and mucous membranes. Poor skin turgor (elasticity). Depressed anterior fontanel. Lack of tears. Sunken eyes socket. Signs of shock: poor peripheral circulation. They may show tachycardia, thin and thready pulse, a low or falling blood pressure, pallor, cool extremities, delayed capillary refilling, hypothermia, oliguria Severity of dehydration: classified into 3 degrees: mild, moderate and severe degree. Table 1. Severity of dehydration mild moderate severe water loss <5% 5-10% >10% (% of BW) <50ml/kg 50-100ml/kg 100-120ml/kg consciousness normal or slight lassitude lethargy (psyche) restlessness restlessness coma skin turgor fair or poor elasticity markedly slight poor decreased (see next page) (go on) mucosa eye socket fontanel tears urine peripheral circulation mild slightly dry slightly sunken slight depression present present fair moderate dry sunken depression decreased oliguria slight poor severe very dry deep sunken deep depression absent anuria collapse cool extremities thin pulse low and dull H.S The types of dehydration According to the osmolarity of remainder of body fluid followed dehydration, the dehydration can be divided into three types: –Isotonic, –hypotonic –hypertonic dehydration. During diarrhea, both water and electrolyte are lost but may not be proportional. The three types of dehydration may be classified by the serum sodium concentration, because sodium is the main component of ECF. Table 2. The types of dehydration Isotonic causes vomiting, diarrhea and poor intake hypotonic hypertonic wrong rehydration excessive intake diarrhea associated sodium or with malnutrition excessive sweat proportional sodium loss= loss of sodium > water loss > loss of water loss of water water loss sodium loss and sodium ECF↓, no ECF→ ICF ICF→ECF circulation is change in ICF ECF↓ ICF↑ better maintained Serum Na 130-150 < 130 >150 (mmol/L) ECF=extracellular fluid ICF= intracellular fluid Isotonic volume of ECF decreased hypotonic severely decreased hypertonic less severely decreased volume of ICF not changed increased decreased symptoms more severe less severe and signs shock occurs easily shock is rare skin color gray gray temperature cold cold cold or warm turgor poor very poor fair feel dry clammy thickened doughy mucosa dry slight moist parched psyche lethargy coma irritability pulse rapid rapid slightly rapid Bp low very low slightly low thirsty yes yes or no polydipsia Metabolic acidosis The more severe the acidosis will be. causes: excessive loss of bicarbonate in intestinal juice. starvation ketosis due to poor intake and malabsorption hypoperfusion and hypotension lead to tissue hypoxia and accumulation of lactic acid decreased excretion of fixed acid due to oliguria. According to the severity of acidosis it could be divided into three degrees. CO2 CP normal 18-27 mEq/L 40-60 vol% mild acidosis 13-18 30-40 moderate 9-13 20-30 severe <9 <20 Clinical manifestations: lassitude, lethargy, coma or irritability. Deep, rapid respiration (Kussmauls breathing) and cool expiratory air. The expiratory air smells like 'acetone.‘ Cherry lips. Nausea, vomiting. Hypokalemia Normal serum potassium is 4-4.5 mmol/L. When serum potassium is less than 3.5mmol/L hypokalemia can be diagnosed. Causes: excessive loss of potassium poor intake The capacity of the kidney to retain K is not as good as that for sodium. During K deficiency, the kidney still excrete certain amounts of potassium. Prior to rehydration, serum K usually remains normal, because: ① Hemoconcentration. ② During acidosis K moves from ICF into ECF. ③ Oliguria reduce the excretion of K. Along with rehydration serum K will gradually fall, because: ① Hemodilution. ②Acidosis is being corrected, K returns from ECF to ICF. ③ K excretion is increased along with urine discharge. ④ Synthesis of glycogen with infused glucose needs K. ⑤Ongoing loss of potassium due to diarrhea. Clinical manifestations of hypokalemia Central nervous system: lassitude Skeletal muscle: weakness, hypotonia , diminished reflexes and even paralysis. Smooth muscle: Abdominal distention with diminished or absent peristalsis. Bowel sound is decreased. Heart: Increased myocardial irritability, presenting as tachycardia, arrhythmia, dull heart sounds. ECG shows prolonged Q-T interval, flat or inverted T waves, prominent u wave and depressed S-T segments. Alkalosis: 2Na+1H ICF ' ECF 3K Hypocalcemia and hypomagnesemia Normal value: Serum calcium is 9-11 mg/dl or 2.2-2.7 mmol/L. When the value is < 7 mg/dl (1.75 mmol/L) hypocalcemia is diagnosed. Serum magnesium: 2.0-3.0 mg/dl or 0.8-1.2 mmol/L. If the concentration is < 1.5mg/dl (0.6 mmol/L) hypomagnesemia is defined. Causes: poor intake. malabsorption. excessive loss of Ca, Mg via diarrhea. prolonged diarrhea or active rickets. Hypocalcemia and hypomagnesemia Prior to rehydration there may be no any hypocalcemic symptoms and sighs due to: ① hemoconcentration. ② increased ionic calcium during acidosis. After rehydration and acidosis being corrected symptoms occur, because: ① hemodilution. ② Ionic calcium decreased after acidosis is corrected Hypocalcemia and hypomagnesemia Manifestations: Tetany and convulsion. If the patient has been given calcium the tetany or convulsion arenot relieved, hypomagnesemia should be considered. Some enteritis caused by specific pathogens. 1. Rotavirus enteritis or autumn diarrhea. Pathogen: Human rotavirus (HRV). Predisposing age: 6 - 24 months. Predisposing seasons: autumn and winter. Suddenly onset with symptoms of common symptoms. low-grade fever and cold, no obvious toxic 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, Some enteritis caused by specific pathogens. 2. ETEC enteritis Sudden onset without significant fever or other systemic symptoms. Main symptoms are diarrhea and vomiting. Frequent diarrhea in large amount. The stool is watery. Dehydration, electrolyte disturbances and acidosis may develop. Self-limited disease with nature course of 3-7 days. 3. Invasive bacterial enteritis. a dysentery-like syndrome that is the same as that caused by shigellar. It is usually abrupt in onset and is characterized by high fever. Frequent diarrhea with mucus, pus and blood. Microscopic findings of stools are leukocytes and erythrocytes in varying amount. Other gastrointestinal symptom includes nausea, vomiting, crampy abdominal pain, tenesmus, fecal urgency. There are sometimes severe systemic toxemia, such as chills, malaise, hyperpyrexia even convulsion or infectious shock. Stool bacterial culture may find the pathogen. Some enteritis caused by specific pathogens. 4. Candid albicans enteritis Patients who have chronic debilitating illness, malnutrition or prolonged treated with antibiotics may catch this disease. It occurs predominately in infants under two years of age. The patient may be associated with thrush. Diarrhea, stool with mucus and many frothes. Chlamydospore, blastospore, candidal filament may be seen under microscope. Differential diagnosis 1.Physiologic diarrhea It occurs in infants apparently fatty, younger than six months, usually breast feeding. Accompanied by eczema. Beside diarrhea the infants have no other symptom and have good appetite and normal weight gain. After solid foods (supplemental food ) are added the stools turn to normal. Differential diagnosis 2. Bacillary dysentery Epidemic data (contact history). Stool bacteria culture. Differential diagnosis 3. Acute necrotizing enterocolitis: which must be treated with surgical therapy in time. Severe systemic toxic symptoms. Obvious bloody diarrhea. Treatment Principle: Regulating and continue feeding. Correcting water and electrolyte disturbances. Reasonable medicine administration. Good care and symptomatic treatment. Dietary therapy Oral fluids may be given unless there is severe vomiting or in advanced condition. For breast-fed infants reduce the frequency of feeding or shorten the feeding time. For bottle-fed infants may start with rice porridge, gruel, diluted milk or skimmed milk. In viral enteritis because of lactase deficiency and defected sodium-coupled-glucose transport. it is necessary to use lactose-free diet. (replace milk with soybean milk or lactose-free formula ). Reasonable medicine administration Antibiotics: is not effective for viral and non-invasive bacterial enteritis. But in cases with severe systemic symptoms such as high fever, antibiotics should be given early, specifically and in full dose. Microcological therapy: restore normal enteric bacteria flora. Reasonable medicine administration Intestinal mucosa protector: which can absorb pathogen and toxin, improve the barrier function of GI wall. WHO/UNICN recent recommendation Provide children with 20mg/d of zinc supplementation for 10-14 days (10mg/d for infants under 6 months old). Reasonable medicine administration Antidiarrheal medicines are ineffective or even dangerous. Such as loperamide, tincture of opium, which may inhibit GI motility, increase the multiplication of bacteria and absorption of toxin. Good care and symptomatic treatment Monitoring water intake and loss. Control infusion rate in different period. Vomiting manage. Abdominal distension manage. FLUID THERAPY Common used fluids and tonicity Non-electrolyte solutions: 5%, 10% Glucose (GS). Because the glucose is discomposed for energy supply after enter the body, the solutions are known as no tonic solution only used in providing water and calorie. Electrolyte solutions 0.9% Natri chloride (Normal saline, NS). It is isotonic. But its chlorine component is more than that in plasma, large amount infusion of NS may lead to hyperchloremia and acidosis. Natri bicarbonate (NB). It is a basic solution with two concentrations that are commonly used: 5% NB is 3.6 tonic solution and 5% NB 1 ml/kg could elevate 1 mEq/L CO2 CP. The isotonic concentration for NB is 1.4%. 10% Kalii chloride. It is 8.9 tonic solution. Oral rehydration salt (ORS) It was advocated by the WHO. Formula of oral rehydration salt: Component amount (grams) NaCl 3.5 NaHCO3 2.5 KCl 1.5 Glucose 20 Water 1000ml It is 2/3 tonic and potassium concentration is 0.15%. Mixed solution Table 3. Components and ingredient of mixed solution Solution component ratio ingredient(ml) NS 10%GS 1.4%NB 10%GS 10%NaCl 5%NB 10%KCl 2:1 isotonic sol. 2 1 500 30 47 500 20 1:1 sol (1/2tonic) 1 1 2:3:1 sol (1/2) 2 3 1 500 15 24 4:3:2 sol (2/3) 4 3 2 500 20 33 1:2 sol (1/3) 1 2 500 15 1:4 sol (1/5) 1 4 500 9 4 500 9 normal maintenance solution (1/3) 1 7.5 Oral fluid therapy Indications: Mild or moderate dehydration. No severe vomiting nor abdominal distention. Replacement volume of deficit requirements is 50ml/kg in mild dehydration, 50-100ml/kg in moderate dehydration, is given within 4-6 hrs. Replacement of abnormal maintenance requirements which is ongoing abnormal loss here is about 30ml/kg, is given within 18 hrs. ORS may be used with unlimited water intake. The fluid is best given in small amount frequently. Potassium concentration in ORS is 20 mEq/L(0.15%), a general dosage for diarrhea. For patients with hypokalemia, additional potassium should be added. Patients with obvious acidosis should be corrected with additional Nat bicarb. For viral enteritis ORS is effective. In viral enteritis stool sodium is about 50 mEq/L, while in the ORS the sodium is 90mEq/L. When administering, additional water should be given. Intravenous fluid therapy Indications: Moderate or severe dehydration. The illness is not relieved by Oral fluid therapy or complicated with severe vomiting. The therapy for the first day. When fluid therapy is talked, the amounts of fluid, the kind of fluid and the infusion rate are three key points in this topic. The total amount of fluid needed for replacement of: preexisting losses ongoing abnormal losses normal losses. Preexisting losses means the body water deficits due to diarrhea and vomiting, by the deficits we evaluated the severity of dehydration. Ongoing abnormal losses due to ongoing diarrhea. The amount of the stools is not readily measurable, it is about 10-30 ml/kg/day, Normal losses means normal maintenance requirements that include urine, feces, sweat and insensible water losses through skin and lungs. This requirement is about 60-80 ml/kg. In summary the total volume of fluid: for mild dehydration 90-120 ml/kg moderate dehydration 120-159 ml/kg severe dehydration 150-180 ml/kg Kind of fluids For preexisting losses: Isotonic dehydration: 1/2 tonics Hypotonic dehydration: 2/3 tonics Hypertonic dehydration: 1/3 tonic For ongoing abnormal losses 1/2 tonic solution is used, For ongoing normal loss 1/3 tonic solution is used. These two ongoing losses go together replenished with 1/2 -1/3 tonic solution. Infusing rates Phase Ⅰ: rapid expansion of plasma volume, which is used in patient with poor peripheral circulation. This phase of treatment is aimed at rapid expansion of extracellular fluid volume, to relieve or prevent shock and to restore renal function. 2:1 solution or 1.4% NB should be used in this phase. This isotonic sodium-containing solution must be given immediately after admission to the hospital. The amount given is 20 ml/kg and injected intravenously within 0.5-1 hr. Infusing rates Phase Ⅱ: For replacement of remaining fluid deficit. It is aimed at correction of dehydration over the next 8-12 hours. The amount and formulation of this phase are dependent upon the severity and type of dehydration. The amount = preexisting losses-the amount of expansion . This amount is about half of total amount. This stage should be completed during the first 8-12 hrs or at an infusing rate of 8-10 ml/kg/hr. Infusing rates Phase Ⅲ: For replenish of ongoing normal and abnormal losses. The infusing rate is decreased to 5 ml/kg/hr in this stage and the remaining fluid would then be given during the following 12-16 hours. The amount = total amount-preexisting losses. (about half of total amount). The kind of fluids: 1/3 tonic solution. Correcting acidosis There are two formulas for calculating the amount of alkaline solution needed: (40-CO2 CP)×0.5×BW(kg)=ml (of 5% N.B) ABE×0.5×BW(kg)= ml (of 5% N.B) We usually give half of the amount calculated and further regulate base on further CO2 CP or blood gas analysis. Replacement of potassium For mild hypokalemia: 200-300 mg/kg. day or 3-4 mEq/kg,d (KCl) severe hypokalemia: 300-450 mg/kg.day or 4-8 mEq/Kg.d Generally the concentration of potassium in the infusion is 27 mEq/L (=KCl 0.2%) and should not exceed 0.3%. For mild cases it may be given orally. Some key points should be paid attention to: K+ should not be administered until the kidneys are functioning (there are urine in bladder or passed urine during 6 hours before admission) The concentration of KCl should be 0.15 -0.3%, < 0.3%. The solution containing K+ can not be injected intravenously. The duration of intravenous infusion of K+ containing solution should > 6-8 hrs. In order to balance K+ between ECF and ICF, K+ losses are usually replaced > 4-6 day's period. Supplement of Calcium and magnesium If patient shows the symptoms of hypocalcemia (tetany or convulsion) calcium should be administered: 10% Cal gluconate 10ml + 10% or 25% glucose 10ml intravenous injection slowly. If the symptom is not improved, magnesium should be given. 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 tonic Sodiumcontaining solutions. The volumes of ongoing abnormal maintenance requirements are dependent on the amount of diarrhea stools. Correcting acidosis and hypokalemia if necessary. CHECKPOINTS Predisposing factors for infants suffering diarrhea. Classification of infantile diarrhea by course and by severity. Mild, moderate and severe dehydration. Characters of rotavirus enteritis. Physiologic diarrhea. Principle for treatment of infantile diarrhea. Formula of oral rehydration salt. Some key points of replacement of potassium.