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Acute Diarrhoea
Ahmed Laving
What’s the problem?
 Diarrhoea major health concern in developing
countries
 4 billion global cases diarrhoea per year
 Mortality down from 4.5 million deaths/yr to 1.8
million deaths/yr since introduction of Oral
Rehydration Solution (ORS) in the late 1970’s
 Mainly affects <2 yr olds
 Most common cause worldwide: Rota virus
infection (up to 40% of inpatient cause of
diarrhoea)
WHO Bulletin 2006
Definitions
 Diarrhoea: three or more loose stools per day
 Acute diarrhoea: diarrhoea lasting less than
14 days
 Persistent diarrhoea: diarrhoea lasting more
than 14 days.
 Dysentery: diarrhoea with visible blood in the
stool
Normal GI Physiology-
Digestion
DUODENUM AND JEJUNUM
Pancreatic enzymes-
Amylase-acts on starches and produces oligo-, di-and tri-
saccharides and alpha dextrins
Exopeptidases -breaks carboxy and amino ends of polypeptides
from the stomach
Nuclease-splits nucleic acid to nucleotides-are then broken
down into nucleosides-then into purine and pyrimidine bases
Lipase-breaks triglycerides into fatty acids & mono-glycerides.
Bile acid activated lipase acts on cholesterol esters of fat
soluble vitamins, phospholipids and triglycerides
Water and Electrolytes
Water
 Little movement in stomach
 Large volumes of water are normally secreted into the small
intestinal lumen, but a large majority of this water is efficiently
absorbed before reaching the large intestine.
Na
 Via Na/Glu and Na/ AA co-transport mechanisms
 Basolateral membrane contains Na/K ATPase for active
transport
Cl
 Enters enterocytes via Na-K-Cl co-transporter in the basolateral
membrane. Cl then secreted back to lumen via protein kinases
e.g. Protein kinase A
Acute Diarrhoea: Pathophysiology
 Villous epithelial damage
 Loss of brush border enzymes
 Immature crypt cells allow net secretion
 Toxins: affect Na/K/ATPase pump
 Net effect: loss of body water, electrolytes, nutrients
 Children more prone to dehydration
 Higher surface to body weight ratio (higher insensible
loss/kg)
 Higher metabolic rate
 Dependent on others for fluids
Acute diarrhoea
 More than 90% of cases of acute diarrhoea
are caused by infectious agents; these cases
are often accompanied by vomiting, fever,
and abdominal pain.
 The remaining 10% are caused by
medications, toxic ingestions, ischemia, and
other conditions.
Types of Diarrhoea
 Osmotic
 Secretory
 Inflammatory
Osmotic Diarrhoea
Osmotic diarrhoea typically results from one of two situations:
1.Ingestion of a poorly absorbed substrate: usually a carbohydrate or
divalent ion. Common examples: mannitol or sorbitol, epson salt
(MgSO4) and some antacids (MgOH2).
2.Malabsorption: carbohydrates the most common but can result from
virtually any type of malabsorption .Example lactose intolerance
from brush border enzyme lactase deficiency.
Lactose also fermented by colonic bacteria, resulting in production of
excessive gas.
A distinguishing feature of osmotic diarrhea is that it stops after the
patient is fasted or stops consuming the poorly absorbed solute
Secretory Diarrhea
 Diarrhea occurs when secretion of water into the
intestinal lumen exceeds absorption.
Vibrio cholerae, produces toxin that activates adenyl
cyclase, causing increase in cAMP within
enterocytes. This results in prolonged opening of
chloride channels allowing uncontrolled secretion of
water from the crypts.
(Cholera toxin also affects enteric nervous system,
resulting in an independent stimulus of secretion.)
 Exposure to toxins from several other types of
bacteria (e.g. E. coli heat-labile toxin) induces the
same response.
Secretory Diarrhea…cont’d
Non-pathogenic agents can induce secretory
diarrhoea by turning on intestinal secretory
machinery, including:
 some laxatives
 hormones secreted by certain types of tumors (e.g.
VIP)
 a broad range of drugs (e.g. antibiotics,
antidepressants)
 certain metals, organic toxins, and plant products
(e.g. arsenic, insecticides, mushroom toxins,
caffeine)
In most cases, secretory diarrhoea will not resolve
during a 2-3 day fast.
Inflammatory & Infectious
Diarrhoea
Results from breach of the GIT barrier
Causes
1. exudation of serum and blood into the lumen
2. widespread destruction of absorptive epithelium
Water absorption becomes very inefficient and
diarrhoea results.
Examples of pathogens:
 Bacteria: Salmonella, E. coli, Campylobacter
 Viruses: rotaviruses, coronaviruses,
 Protozoa: coccidia species, Cryptosporium, Giardia
Epidemiologic classifications
Travelers diarrhoea
 Nearly 40% of tourists to endemic regions of
Latin America, Africa, and Asia develop
traveler's diarrhoea.
 Commonly due to ETEC, Campylobacter,
Shigella, and Salmonella.
 Other agents are Giardia and Cyclospora
Diarrhoea following food
poisoning
Diarrhoea after food eaten at a picnic, banquet, or
restaurant may suggest infection with:
 Salmonella, Campylobacter, or Shigella: from
chicken
 EHEC (O157:H7): from undercooked hamburger
 Bacillus aureus: from fried rice
 Staphylococcus aureus or Salmonella: from
mayonnaise or creams
 Salmonella: from eggs; and
 Vibrio species, Salmonella, or acute hepatitis A:
from seafood (especially raw)
Immunodeficient persons
Primary or secondary immunodeficiency states:
 Common enteropathogens often cause a more
severe and protracted diarrhoeal illness
 Opportunistic infections, e.g. Mycobacterium
species, viruses (CMV, adenovirus, and HSV),
protozoa (Cryptosporidium, Isospora belli,
Microsporidia and Blastocystis hominis).
 In patients with AIDS, agents transmitted venereally
per rectum (e.g., Neisseria gonorrhoeae,
Treponema pallidum, Chlamydia) may cause
proctocolitis.
Summary
 Profuse watery diarrhoea secondary to small bowel
hypersecretion occurs with ingestion of preformed bacterial
toxins, enterotoxin -producing bacteria, and enteroadherent
pathogens.
 Diarrhoea associated with marked vomiting and minimal or no
fever may occur abruptly within a few hours after ingestion of
toxins; vomiting is usually less, and abdominal cramping or
bloating is greater; fever is higher with the latter. Cytotoxin -
producing and invasive microorganisms all cause high fever and
abdominal pain.
 Invasive bacteria and E histolytica often cause bloody diarrhoea
(dysentery).
 Yersinia invades the terminal ileal and proximal colon mucosa
and may cause especially severe abdominal pain with
tenderness mimicking acute appendicitis.
Zinc and Diarrhoea
 Zinc is lost in greater amount during diarrhoea
 Important for cell multiplication
 Supplementation results in faster regeneration of the
gut epithelium
 Enhances immune response early clearance of
diarrhea pathogen from the intestine
 Increases level of enterocyte brush border enzymes
 Reduces stool volumes (18-53%) and duration
(25%) of ongoing diarrhea
 Lowers the incidence of diarrhea in the following 2-3
months by 18-20%

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Acute Diarrhoea.pptx

  • 2. What’s the problem?  Diarrhoea major health concern in developing countries  4 billion global cases diarrhoea per year  Mortality down from 4.5 million deaths/yr to 1.8 million deaths/yr since introduction of Oral Rehydration Solution (ORS) in the late 1970’s  Mainly affects <2 yr olds  Most common cause worldwide: Rota virus infection (up to 40% of inpatient cause of diarrhoea) WHO Bulletin 2006
  • 3. Definitions  Diarrhoea: three or more loose stools per day  Acute diarrhoea: diarrhoea lasting less than 14 days  Persistent diarrhoea: diarrhoea lasting more than 14 days.  Dysentery: diarrhoea with visible blood in the stool
  • 4. Normal GI Physiology- Digestion DUODENUM AND JEJUNUM Pancreatic enzymes- Amylase-acts on starches and produces oligo-, di-and tri- saccharides and alpha dextrins Exopeptidases -breaks carboxy and amino ends of polypeptides from the stomach Nuclease-splits nucleic acid to nucleotides-are then broken down into nucleosides-then into purine and pyrimidine bases Lipase-breaks triglycerides into fatty acids & mono-glycerides. Bile acid activated lipase acts on cholesterol esters of fat soluble vitamins, phospholipids and triglycerides
  • 5. Water and Electrolytes Water  Little movement in stomach  Large volumes of water are normally secreted into the small intestinal lumen, but a large majority of this water is efficiently absorbed before reaching the large intestine. Na  Via Na/Glu and Na/ AA co-transport mechanisms  Basolateral membrane contains Na/K ATPase for active transport Cl  Enters enterocytes via Na-K-Cl co-transporter in the basolateral membrane. Cl then secreted back to lumen via protein kinases e.g. Protein kinase A
  • 6. Acute Diarrhoea: Pathophysiology  Villous epithelial damage  Loss of brush border enzymes  Immature crypt cells allow net secretion  Toxins: affect Na/K/ATPase pump  Net effect: loss of body water, electrolytes, nutrients  Children more prone to dehydration  Higher surface to body weight ratio (higher insensible loss/kg)  Higher metabolic rate  Dependent on others for fluids
  • 7. Acute diarrhoea  More than 90% of cases of acute diarrhoea are caused by infectious agents; these cases are often accompanied by vomiting, fever, and abdominal pain.  The remaining 10% are caused by medications, toxic ingestions, ischemia, and other conditions.
  • 8. Types of Diarrhoea  Osmotic  Secretory  Inflammatory
  • 9. Osmotic Diarrhoea Osmotic diarrhoea typically results from one of two situations: 1.Ingestion of a poorly absorbed substrate: usually a carbohydrate or divalent ion. Common examples: mannitol or sorbitol, epson salt (MgSO4) and some antacids (MgOH2). 2.Malabsorption: carbohydrates the most common but can result from virtually any type of malabsorption .Example lactose intolerance from brush border enzyme lactase deficiency. Lactose also fermented by colonic bacteria, resulting in production of excessive gas. A distinguishing feature of osmotic diarrhea is that it stops after the patient is fasted or stops consuming the poorly absorbed solute
  • 10. Secretory Diarrhea  Diarrhea occurs when secretion of water into the intestinal lumen exceeds absorption. Vibrio cholerae, produces toxin that activates adenyl cyclase, causing increase in cAMP within enterocytes. This results in prolonged opening of chloride channels allowing uncontrolled secretion of water from the crypts. (Cholera toxin also affects enteric nervous system, resulting in an independent stimulus of secretion.)  Exposure to toxins from several other types of bacteria (e.g. E. coli heat-labile toxin) induces the same response.
  • 11. Secretory Diarrhea…cont’d Non-pathogenic agents can induce secretory diarrhoea by turning on intestinal secretory machinery, including:  some laxatives  hormones secreted by certain types of tumors (e.g. VIP)  a broad range of drugs (e.g. antibiotics, antidepressants)  certain metals, organic toxins, and plant products (e.g. arsenic, insecticides, mushroom toxins, caffeine) In most cases, secretory diarrhoea will not resolve during a 2-3 day fast.
  • 12. Inflammatory & Infectious Diarrhoea Results from breach of the GIT barrier Causes 1. exudation of serum and blood into the lumen 2. widespread destruction of absorptive epithelium Water absorption becomes very inefficient and diarrhoea results. Examples of pathogens:  Bacteria: Salmonella, E. coli, Campylobacter  Viruses: rotaviruses, coronaviruses,  Protozoa: coccidia species, Cryptosporium, Giardia
  • 13. Epidemiologic classifications Travelers diarrhoea  Nearly 40% of tourists to endemic regions of Latin America, Africa, and Asia develop traveler's diarrhoea.  Commonly due to ETEC, Campylobacter, Shigella, and Salmonella.  Other agents are Giardia and Cyclospora
  • 14. Diarrhoea following food poisoning Diarrhoea after food eaten at a picnic, banquet, or restaurant may suggest infection with:  Salmonella, Campylobacter, or Shigella: from chicken  EHEC (O157:H7): from undercooked hamburger  Bacillus aureus: from fried rice  Staphylococcus aureus or Salmonella: from mayonnaise or creams  Salmonella: from eggs; and  Vibrio species, Salmonella, or acute hepatitis A: from seafood (especially raw)
  • 15. Immunodeficient persons Primary or secondary immunodeficiency states:  Common enteropathogens often cause a more severe and protracted diarrhoeal illness  Opportunistic infections, e.g. Mycobacterium species, viruses (CMV, adenovirus, and HSV), protozoa (Cryptosporidium, Isospora belli, Microsporidia and Blastocystis hominis).  In patients with AIDS, agents transmitted venereally per rectum (e.g., Neisseria gonorrhoeae, Treponema pallidum, Chlamydia) may cause proctocolitis.
  • 16. Summary  Profuse watery diarrhoea secondary to small bowel hypersecretion occurs with ingestion of preformed bacterial toxins, enterotoxin -producing bacteria, and enteroadherent pathogens.  Diarrhoea associated with marked vomiting and minimal or no fever may occur abruptly within a few hours after ingestion of toxins; vomiting is usually less, and abdominal cramping or bloating is greater; fever is higher with the latter. Cytotoxin - producing and invasive microorganisms all cause high fever and abdominal pain.  Invasive bacteria and E histolytica often cause bloody diarrhoea (dysentery).  Yersinia invades the terminal ileal and proximal colon mucosa and may cause especially severe abdominal pain with tenderness mimicking acute appendicitis.
  • 17. Zinc and Diarrhoea  Zinc is lost in greater amount during diarrhoea  Important for cell multiplication  Supplementation results in faster regeneration of the gut epithelium  Enhances immune response early clearance of diarrhea pathogen from the intestine  Increases level of enterocyte brush border enzymes  Reduces stool volumes (18-53%) and duration (25%) of ongoing diarrhea  Lowers the incidence of diarrhea in the following 2-3 months by 18-20%