PBL2 Flashcards
(24 cards)
ebola
this is a viral infection that infects its patients over a number of days eventually leading to haemorrhage and death, it causes symptoms such as diarrhoea and vomiting, it is spread by fluid contact and direct contact
cholera
cholera is a bacterial disease that is infectious and can be fatal, it infects the small intestine and can cause severe vomiting and diarrhoea which can leads to dehydration. It is contracted from infected watery supplies
in vitro
this is testing in a test tube or glass, this is differentiated from in vivo which is using organisms and doing testes inside the organism
diarrhoea
this is an abnormal passage of loose liquid stools more than 3 times a day, the volume of stool has to be over 250g
- acute if it lasts less than 14 days
mechanism of action of cholera toxin
- In the chloral toxin it is made out of two subunits
- It is gamma shaped
- The alpha subunit binds to adenyl cyclase
- This causes it to activate the ATP and convert it to cAMP
- The amount of cAMP increases within the cell
- This activates the CFTR channel
- This causes the increased secretion of chloride ions into the lumen of the small intestine
- Sodium follows out down the electrical gradient in order to maintain electroneutrality of the lumen of the small intestine
- Where sodium goes water follows
- Therefore, the amount of water that is in the small intestine increases largely
- There is decreased absorption of the Na and Cl as this transporter is blocked
- Na glucose transporter is not affected
what are the 4 different types of diarrhoea
- Osmotic diarrhoea
- Secretory diarrhoea
- Inflammatory and infectious diarrhoea
- Diarrhoea that is associated with deranged motility
describe osmotic diarrhoea
- Absorption of water in the intestines is dependent on adequate absorption of solutes, osmotic diarrhoea results in an increase of non-absorbed solutes in the lumen
Results from two situations
1. Ingestion of a poorly absorbed substrate – this is usually a carbohydrate or divalent enzyme
2. Malabsorption – this is when you have the inability to absorb certain nutrients such as carbohydrates, a common one is the inability to absorb lactose resulting in a lactose intolerance which is caused by the deficiency in the brush border enzyme lactase, the lactose remains in the intestinal lumen and this causes water to leave and move into the intestinal lumen
Distinguishing feature - It stops after the patient has fasted or stops consuming the absorbed solute
due to
- coeliacs disease
- lactose intolerance
- somatic laxatives
describe secretary diarrhoea
- Large volumes of water are normally secreted in the small intestine lumen but these are normally absorbed before reaching the large intestine
- Secretory diarrhoea is caused when secretion of water in the intestine in the lumen exceeds the volume of water that is being absorbed
- Lethal as can cause dehydration, these people have to be hydrated
- (decreased absorption and increased secretion)
what causes secretary diarrhoea
- Chloera
- E.coli
- Some laxatives
- Hormones secreted by certain types of tumours
- Range of drugs such as some types of asthma medications
- Certain metals, organic toxins and plant products
describe inflammatory diarrhoea
- This happens when the epithelium is disrupted due to microbial or viral pathogens
- Destroys absorptive epithelium therefore absorption of water is inefficient
The immune response that the body gives to these pathogens contributes to the diarrhoea that develops, white blood cells lead them to secrete inflammatory mediators and cytokines which can stimulate secretion
Reactive oxygen species form leukocytes can damage or kill intestinal epithelial cells which replace brush border enzymes with transporters that are necessary for absorption of nutrients and water
what causes inflammatory diarrhoea
- Infectious pathogens such as….
- • Bacteria: Salmonella, E. coli, Campylobacter
- • Viruses: rotaviruses, coronaviruses, parvoviruses (canine and feline), norovirus
- • Protozoa: coccidia species, Cryptosporium, Giardia
- Inflammation – crohsn and ulcerative colitis
describe diarrhoea associated with deranged motility
- Increased propulsion absorbed in many types of dirrohea
- Increase transit time results in decreased absorption and therefore results in diarrhoea
due to
- IBS
- hyperthryodisim
- drugs
describe oral rehydration therapy as a treatment for diarrhoea
Use oral rehydration therapy as a treatment
- It uses the sodium chloride and glucose transporter as this is unaffected by the cholera toxin this means that it can absorb solutes and therefore water will passively diffuse in once sodium is absorbed into the cell therefore reducing the amount of water that is in the lumen
describe what the bicarbonate does
- Diarrhoea causes a net loss of bicarbonate from the gut with the diarrhoea
- Therefore, this would cause metabolic acidosis due to the loss and lowering of bicarbonate
- The amount of hydrogen ions that the body retains by the kidney keeping hydrogen ions and not excreting them and by respiratory compensation increases hydrogen ion concentration
- Only used for the correction of metabolic acidosis of diarrhoeal dehydration
name the different sources of fluid in the body
- The small intestine absorbs amount 8L of fluid a day
- The stomach absorbed about 2L
- The colon absorbs 1400L a day
- ingested water (2 liters)
- liver and pancreatic secretions ( 2 liters)
- salivary gland secretions (1.5 liters)
- secretions by glands of the stomach and small intestines (3.5 liters).
- Small intestine absorbs 8.5L
- Colon 400ml
- Faeces 100ml
describe absorption that happens in the small intestine
Absorption in the small intestine
- There is a sodium potassium ATPase transporter, this causes 2 Na to be pumped out and 3 potassium to be pumped in
- This allows the absorption of sodium chloride and glucose, as sodium is absorbed water follows and therefore this allows the absorption of water
- This ATPase transporter is inhibited by cAMP therefore it is inhibited when the cholera toxin increases
describe secretion that happens in the small intestine
- CFTR secretes chloride out of the cell this is activated by cAMP (apical membrane in crypts)
- Therefore, when cAMP increases when the cholera toxin is present it causes more chloride excretion
what is the role of water in the gut
- Hydrolysis
- Propulsion of food
- Forms mucus with mucin in order to protect the stomach epithelium and prevent it from self-absorption
- Facilitation of absorption (brings the products of digestion into close proximity to microvilli)
how do the treatments work in the treatment of diarrhoea
- When you add the cholera toxin the amount of sodium in the cell decreases down to 10 this is because it is entering the lumen in order to keep it electroneutral, this causes the water intracellular volume to decrease as water follows sodium
- When sodium potassium and chloride are present it does not return as sodium is not absorbed due to the SGLT1 protein channel not being active
- Glucose needs to be present as it is pumped out of the cell that is reabsorobed via the SGLT1 protien channel, if there is no glucose present then this channel does not work therefore no reabsorption of sodium this means that there is no reabsorbed of water, this is why when glucose is present it nearly goes back to the original concentration
What are the sources of fluid that enter the small intestine
- oral intake
- saliva
- bile
- gastric jucie
- pancreatic jucie
- intestinal juice
how does absorption of sodium glucose and water happen in a villus enterocyte
on the apical membrane
- sodium glucose transporter transports sodium and glucose into the cel
baso lateral membrana
- potassium sodium transporter transports potassium into the cell and sodium into the interstitial fluid
- glucose is transported out of the cell into the interstitial fluid
- water transported via paracellular transport into the interstitial fluid
how does secretion of sodium glucose and water happen in a crypt enterocyte
- on the basolateral membrane there is the potassium sodium transporter this transports sodium into the interstitial layer and then it goes back into the lumen
- this is because on the apical membrane there is a chloride transporter CFTR which is transporting chloride into the. lumen of the gut
- sodium makes sure that the gut stays electroneutral, this causes water to go into the gut
- the entry the chloride into the cell is caused by the sodium, potassium, chloride transporter on the basolateral membrane
describe oral rehydration therapy
- this card
Essential components: Sodium chloride + glucose
SGLT on apical membrane of enterocytes need BOTH Na+
and glucose for co-transport
Their absorption creates an osmotic gradient for water to
diffuse from lumen into capillaries
Potassium added to correct hypokalaemia
– Low K+ can cause muscle cramping, weakness and
arrhythmias
Bicarbonate added to correct metabolic acidosis
Apart from gastric juice, all the other secretions into the
bowel are alkaline, so intestines have high HCO3- levels
This is lost in diarrhoea → can cause metabolic acidosis
what are other treatments for diarrhoea
Antimotility agents (e.g. loperamide)
Relief for mild-moderate diarrhoea
Antibiotics
Generally not used; can cause diarrhoea
For cholera: only if severely dehydrated
Treat underlying cause for chronic diarrhoea
