Group 5, Section B1

OUTLINE
I. Diarrhea II. Presentation of Case 1 III. Mechanism of Diarrhea IV. Management VI. Cholera

I. Diarrhea
A. Definition Defined as passage of abnormally liquid or unformed stools at an increased frequency > 200-300 gm/day > 3 stools/day

I. Diarrhea

I. Diarrhea
Classification: Duration of the illness Mechanism Severity Acute - < 2 weeks Persistent- 2 to 4 weeks Chronic- > 4 weeks Stool Characteristic

I.Diarrhea
Acute Diarrhea
common cause of death in developing countries. < 2 weeks

Causes 90 % - INFECTIOUS AGENTS 10 % - Medications , Toxic ingestions, Ischemia

I.Diarrhea
Chronic Diarrhea
> 4 weeks
Caused by: Infection Allergy IBD (inflammatory bowel disease) or Crohns disease.

I. Diarrhea
Types of Diarrhea
Secretory diarrhea
Infections increase the secretion of water and electrolytes which override the re-absorptive ability of the large intestine. Cause:
Bacterial Viral Protozoan Drugs (Laxatives)

I.Diarrhea
Osmotic diarrhea - Maldigestion and Malabsorption - Water and electrolyte retention in Large Intestine Causes:
Lactose Intolerance Malabsorption Pancreatic disease

The most common pathogens causing diarrhea are :

Rotavirus (15-25%)

Enterotoxigenic Escherichia coli 10-20%

Shigella 5-15%

Campylobacter jejuni 10-15%

I.Diarrhea
Transmission
Most of the diarrheal agents are transmitted by the fecal-oral route Airborne (viruses) Nosocommial transmission is possible Shigella (the bacteria causing dysentery) is mainly transmitted person-to-person

I. Diarrhea
Signs and Symptoms Loose and watery stool Increase in frequency of bowel movements Presence of mucus, pus, blood or excessive amounts of fat Dehydration

I.Diarrhea
Person at Risk:
Cholera: 2 years and above, uncommon in very young infants Shigellosis: more common in young children aged below 5 years Rotavirus diarrhea: more common in young infants and children aged 1-2 years E. coli diarrhea: can occur at any age Amebiasis: more common among adults

I.Diarrhea
Management: A. Prevention Hand washing Proper preparation and storage of food Clean water source Clean environment Proper waste management

Management
B. Non-pharmacological Diet
Avoid high fiber diet, caffeine, alcohol Continuing solids Improve mothers diet Continue breast feeding as usual
during and after rehydration therapy.

Rehydration
50-200ml/kg/day of ORAL REHYDRATION SOLUTION (ORS)

Case I Discussion
A mother brought her 10-months old, 8-kg daughter to a health center because of diarrhea of one day duration which occurred 4 times. There was no accompanying vomiting. She has been breastfed since birth. At 5 months old. Lugaw with fish and vegetables were started. At the onset of diarrhea, the mother stopped breastfeeding and giving of solid foods and instead shifted to giving am with sugar. The child is alert, with good skin turgor and adequate urine output.

Metabolic Changes Observed in Diarrhea

QUESTION 1: Describe the sequence of the various metabolic changes observed in diarrhea and correlates these to the clinical manifestations observed in the patient.

Normal Intestinal Physiology

Osmotic diarrhea

Secretory diarrhea

Motility-related diarrhea

Exudative diarrhea

oMaldigestion o Osmotic laxatives o Lactose intolerance o Fructose malabsorptionon

water is drawn into the bowels

 Osmotic
Digestive enzyme deficiencies Ingestion of un-absorbable solute

Gastrointestinal function and motility

INCREASED GI FUNCTION AND MOTILITY - movement of food, water absorption - Parasympathetic NS increases GI motility - Bacteria causes the Crypts of Liberkuhn to secrete large amounts of choride and bicarbonate. Osmotic movement of water
propels the movement of stool out of the system.

LOOSE WATERY STOOL

Alteration in fluid volume

DEFICIENT FLUID VOLUME secretion of water by the Crypts of Liberkuhn in the small intestine causes the fecal matter to travel faster to anus.

DEHYDRATION

Acid- base balance

Metabolic acidosis- precursor to diarrhea Hypokalemia- prolonged diarrhea
< 3.0 meq/L- muscle weakness, muscle cramps and cardiac arrhythmias.

Composition
Semisolid or loose stool Mucous Blood

Evaluation of nutritional status and state of hydration of the patient.

QUESTION 2: Evaluate the nutritional status and state of hydration of the patient (use growth chart and assessment of hydration table). Compute for the ideal weight for age of the patient.

DATA:
Sex: Female Age: 10 months old Weight: 8 kg Does the young infant have diarrhea? YES For how long? One day Frequency : Four times

Mild

Moderate

Severe

-Irritable

-Irritable -Weak pulse -Some reduction in urine volume

-Moribund, apathetic -Peripheral circulatory failure (cold extremities, warm body, excessive blanching, weak pulse) -Marked reduction in urine volume
Thirsty -Fontanelle markedly depressed -Eyeballs markedly sunken -Facies markedly dry and pinched -Buccal mucosa dry -Lips parched -Loss of skin turgor (except hypernatremic in which it may not be variety prominent)

Thirsty

Thirsty -Fontanelle depressed -Eyeballs sunken -Facies dry and pinched -Buccal mucosa dry -Lips parched -Loss of skin turgor (except in in hypernatremic variety)

ASSES AND CLASSIFY SICK CHILD AGED 2 MONTHS UP TO 5 YEARS

ASK: Does the child have diarrhea? If YES, ask: For how long? Is there blood in the stool?

Look and feel: Look at the childs general condition. Is the child: Abnormally sleepy or difficult to awaken? Restless and irritable? Look for sunken eyes.

 Offer the child fluid. Is the child: Not able to drink or drinking poorly? Drinking eagerly, thirsty?

Pinch the skin of the abdomen. 10

Does it go back: Very slowly (longer than 2 seconds)? Slowly?

Classify Diarrhea

If diarrhea for 14 days or more

If blood in stool

 Based on Integrated Management of childhood Illness the infant is considered NO DEHYDRATION status. Based on the assessment that the child is alert, with good skin turgor and adequate urine output. Computation: Formula: [ AGE (month) + 9] / 2 ( weight for kilograms) WHO Weight standards = 10 months + 9/ 2 = 9.5 kg The infant has poor nutritional status based on her low weight for age.

Cycle of Malnutrition and Diarrhea

Impaired absorption of Na

NET SECRETION

Cl , HCO3

+++++

 Exudative
Inflammation Decreased colonic reabsorption

Increased motility
Decreased transit time

CONTINUATION Evaluation of nutritional status and state of hydration of the patient.

QUESTION 3: Determine the adequacy of the patients diet before and during diarrhea relate this to the cycle of malnutrition and diarrhea.

 Before diarrhea: inadequate. 10 months- eat variety of foods (rice and meat products)
sustain her nutritional requirement to boost her immune system thus preventing malnutrition.

During diarrhea: inadequate

Discontinue breast feeding am or rice water was given- alternative for starch requirement, supplementary source of fluid and electrolytes WHO: Am has the nutritional advantage of providing more calories during rehydration than does ORS

Advantages of breastfeeding and oral rehydration solution.

QUESTION 4: What advice should be given to the patients mother regarding breastfeeding, use of home fluids/oral rehydration solutions and other nutritional support for the patient.

ADVANTAGES A. Breastfeeding/Colostrums -Continued during diarrhea. -As often as the infant desires -Less prone to diarrhea. -Low buffering capacity, stools of breastfed babies are acidic. -Low E. coli count, high Lactobacillus bitidus -Viable phagocytes, IgA and IgM which protect against most enteropathogens -Better growth performance.
Has right amount of fat, sugar, water, and protein that is needed for a baby's growth and development -Greater Immune Health: IgA antibodies against infections on the childs intestinal flora. Side Note: The quality of a mother's breast milk may be compromised by alcoholic beverages, caffeinated drinks, marijuana, methamphetamine, heroin, and methadone.

Advantage B. Oral Rehydration Solutions (ORS) -prepared at home by mixing eight level teaspoonfuls of cane sugar (40 grams of sucrose), one level teaspoonful of table salt (five grams of NaCl) with or without a lemon squeezed in one litre of potable water. Since 2 g of sugar releases I g of glucose, 40 g of sucrose is used. Alternatively a 3 finger pinch (upto the first crease) of table salt and closed fistful of cane sugar are mixed in half a litre of water. -Replenishes lost essential fluids that maintain body homeostasis. -patient treated with ORS do not require an intravenous access, a potentially painful and difficult procedure in young children. Although effective in rehydration, it do not decreases stool volume because of the relatively high osmolality of glucose they contain.

Advantage
C. Nutritional Support

Zinc

Potassium

Greatly reduces the severity and duration of diarrhea Influences osmotic balance between cells and interstitial fluid (Na-KATPase Pump)

 QUESTION 5: What biochemical significance if any, can be given to the use of am with sugar in diarrheic patients?

 Effective treatment for diarrhea Rice starch is rapidly converted to glucose by pancreatic amylase and brush border hydrolases. Rice powder, being mostly starch, releases more than twice the amount of glucose when digested than is present in standard ORS solution
Glucose provides energy and also draws water that helps to replenish the water that are lost in the stool.

 Sodium- glucose transport mechanism

High concentration of sodium, water and glucose in the gut lumen High concentration will enter the epithelial cell using SGLT1 carrier protein Glucose and sodium entered the cell water will follow through Where sodium goes, water follows

Outline
I. Definition II. Presentation of the Case III. Biochemical Aspect of Cholera IV. Mode of Transmission V. Signs and Symptoms VI. Diagnosis and Treatment

WHAT is

CHOLERA?
Acute Intestinal infection Caused by an enterotoxin released by bacterium, Vibrio cholera Profuse watery diarrhea

Vibrio cholerae
no known animal hosts attach themselves easily to the shells of crabs, shrimps and other shellfish Fecal contamination

Vibrio Cholerae
2 out of 150 serotypes of cholera toxin: O1 and O139

Case 2:
A 21-year-old female medical student at FEU-NRMF suddenly began to pass profuse watery stools continuously. This was associated with 6 episodes of vomiting of previous ingested food, her general condition declined abruptly, and she was rushed to the FEU-NRMF emergency room. On admission, she was cyanotic, skin turgor was poor, with blood pressure of 70/50 mmHg palpatory, her pulse was weak and rapid. The ER physician on duty diagnosed her as acute gastroenteritis probably viral T/C cholera, he took some blood and stool sample and was treated immediately.

BIOCHEMICAL BASIS OF CHOLERA

Biochemical Basis
2 subunits of Enterotoxin: 1. one A subunit

2. five B subunits

Biochemical Basis
2 subunits of Enterotoxin: 1. one A subunit a. one A1 peptide b. one A2 peptide 2. five B subunits

A1
A2

Five B subunits

Enterotoxin

Ganglioside GM1

Extracellular Space 1

Enterotoxin

Ganglioside

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin

Ganglioside

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin

Ganglioside

G Protein 3

Inactive Adenylate Cyclase

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

How G Protein normally works?

G Protein

Biochemical Basis

Biochemical Basis

Biochemical Basis

Biochemical Basis

 video

Extracellular Space 1

Enterotoxin

Ganglioside

Adenylate cyclase

NAD

Adenylyl cyclase

G Protein 3

Inactive Adenylate Cyclase

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

ADP-Ribosylation ADENYLATE CYCLASE

NAD Nicotinamide ADP ribose

ADP-Ribosylation ADENYLATE CYCLASE

NAD Nicotinamide ADP ribose + G protein

ADP-Ribosylation ADENYLATE CYCLASE

NAD Nicotinamide ADP ribose + G protein
A1

ADP-Ribosylation ADENYLATE CYCLASE

NAD Nicotinamide ADP ribose + G protein

A1
G protein ADP Ribose

+ nicotinamide

ADP-Ribosylation ADENYLATE CYCLASE

NAD Nicotinamide ADP ribose + G protein

G protein ADP Ribose

+ nicotinamide

= ACTIVATE ADENYLYL CYCLASE

Extracellular Space 1

Enterotoxin

Ganglioside

Adenylate cyclase

NAD

Adenylyl cyclase

G Protein 3

Inactive Adenylate Cyclase

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin

Ganglioside

Adenylate cyclase

NAD

Adenylyl cyclase

G Protein 3

Active Adenylyl Cyclase

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin

Ganglioside

2 4 CAMP ATP Adenylyl Cyclase 3

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

ATP

Active Adenylyl Cyclase

cAMP
(cyclic Adenosine Monophosphate)

Extracellular Space 1

Enterotoxin

Ganglioside

2 4 CAMP ATP Adenylyl Cyclase 3

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin

Ganglioside

Protein Kinase 2 4 CAMP ATP Adenylate Cyclase 3 5

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin Cl

Ganglioside 6

CFTR

Protein Kinase 2 4 CAMP ATP Adenylate Cyclase 3 5

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin Na Cl

Ganglioside 6

CFTR

Protein Kinase 2 4 CAMP ATP Adenylate Cyclase 3 5

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

Extracellular Space 1

Enterotoxin Na Cl

H2O
Na, H2O

Ganglioside 6

CFTR

7 8

Protein Kinase 2 4 CAMP ATP Adenylate Cyclase 3 5

G Protein

Epithelial cell of the Small Intestine

Interstitial Spce

BLOOD VESSEL

V. Cholera
Uses NAD to transform the G protein Inactivates the GTPase function of G protein Adenylyl cyclase is activated for longer period 100 fold increase in cAMP Activation of ion channels Ions flow out and water follows