Diarrhoea mechanisms

Question 1

Define diarrhoea

Answer 1

• 3 watery stools or more per day.

Question 2

Describe the pathogenesis of osmotic diarrhoea. Also mention how lactose intolerance can cause this.

Answer 2

• this is brought about by increased amounts of poorly absorbable, highly osmotically active solutes
  
  • This is usually a carbohydrate
    
    • examples include mannitol or sobitol, epson salts, antacids
  • lactose in some patients cannot be properly absorbed - causing it to remain in the lumen
  • lactose is highly osmotically active
  • Because of this, water is retained in the GIT lumen
  • lactose is also fermented by GI bugs, causing gas

Question 3

Describe the pathogenesis of secretory diarrhoea. Name classic bacteria that can cause this.

Answer 3

• it is normal for water to be secreted into the GI lumen when chyme enters - this is not surprising as it will be full of osmotically active substances that will pull water in - as these substances are absorbed, water will also be reabsorbed.
• In secretory diarrhoea, there is INCREASED secretion of fluids and decreased absorption
• Various bacteria can cause this
  
  • E.coli can produce themolabile or thermostable toxin, C.difficile toxin
• Cholera toxin causes activation of intracellular adenylyl cyclase, generating cAMP
  
  • this causes lots of activation of the CFTR channel, drawing chloride in the lumen - to counteract this and confer a charge balance in the lumen, sodium also moves into the lumen - which of course also draws water into the lumen
    
    • it is also thought that cholera toxin loosens tight junctions

Question 4

Explain how inflammatory diarrhoea occurs. State causes, including bacterial

Answer 4

Inflammatory diarrhoea is defined by mucosal destruction.

it results in ion imbalance and thus a loss of fluid - your absorption of fluid and electrolytes is fucked - examples include cytotoxin producing bacteria like the bacteria shigella - which causes cell death - leading to ulceration and further inflammation.

It can also be caused by certain diseseases that damage the mucosa (ulcerative colitis, chron’s disease).

Question 5

Rotovirus can also cause diarrhoea. How does it do this?

Answer 5

• Rotavirus primarily infects intestinal villus enterocytes and crypt cells are spared
• occurs due to virus-mediated destruction of absorptive enterocytes, virus-induced downregulation of the expression of absorptive enzymes - giving a reduced capacity for lumen absorption, and functional changes in tight junctions between enterocytes that lead to paracellular leakage
• There is a secretory component of rotavirus diarrhea that is thought to be mediated by activation of the enteric nervous system and the effects of NSP4—the first described virus-encoded enterotoxin
  
  • from activation of cellular Cl− channels, which increases secretion of Cl− and consequently water

Question 6

Approximately 2 liters of fluid are ingested per day. Salivary secretions, gastric secretions, bile, pancreatic secretions and intestinal secretions all add up to about ???????mL.

Most of this is reabsorbed by the small intestine, about ?????? ml, with the colon absorbing about ???????, leaving only about ????? of water that is excreted in feces.

Answer 6

9000

8000

1200

100-150ml

Question 7

Describe the ways in which sodium can be absorbed from the GI lumen

Answer 7

• first key step for sodium absorption, is that sodium is sent out into the interstital fluid and paracellular spaces via the basal and lateral walls of the cell via a Sodium/potassium pump
  
  • Some sodium can also be absorbed with chloride ions (they are passively dragged by the positive electrical charges of the sodium ions)
  • This active transport of sodium greatly reduces the sodium concentration inside the cell to a low value
  • Because sodium concentration in chyme is usually much higher, this sodium will move into the enterocytes via sodium channels - will also drive water absorption trans and paracellularly.
• Sodium can also be transported alongside other dietary substances - such as glucose, amino acids and also with an ANTIPORTER - with hydrogen. - all of these methods provide more sodium that can be excreted into the interstitial fluid and paracellular fluid.

Question 8

How is potassium absorbed - in both small and large intestine.

Answer 8

• in small intestine it is absorbed passively
  
  • lumen potassium will be higher than that of the interstitial fluid - so potassium will be absorbed paracellularly.
• in large intestine via Potassium/proton pump

Question 9

What hormone released by the adrenal glands, increases sodium absorption in the intestinal eptihelium?

Answer 9

Aldoesterone

Question 10

Chloride ions are primarily absorbed in the upper part of the small intestine. Explain what other ion is important in driving this, and how it does so. Also name an important cholirde antiporter.

Answer 10

Sodium has key role.

When sodium ions are absorbed into epithelial cells and then pumped out, this creates electropositivity in the paracellular spacs, and electronegativity in the GI lumen. As a result, chloride ions move along this electrochemical gradient.

Cholride-bicarbonate antiporter.

Question 11

What are major sources of bicarbonate in the small bowel? Explain the process by which bicarbonate is absorbed; mentioning how it is coupled with the sodium/hydrogen antiporter.

Answer 11

• bicarbonate is normally in high quantities in the lumen because of it’s presence in both pancreatic secretions, bile and secretion by brunner’s glands
• When sodium is absorbed, hydrogen ions can simultaenously be secreted
  
  • as a result, this hydrogen combines with bicarbonate to form Carbonic acid
  • This can dissociate to form water and cabron dioxide
  • Water can be absorbed as per normal means with sodium, whilst carbon dioxide and be readily absorbed into the blood
  • this process is known as the active absorption of bicarbonate ions

Question 12

What hormone that regulates Vitamin D is important in reuglating the role of calcium absorption in the small intestine?

Answer 12

PTH

Question 13

Explain the following blood tests results given that patient has had diarrhoea + infection

Answer 13

• Given the antibiotics, she has lkely had some kind of infection - which has potentially
• Abnromailities are low potassium, low urine and high creatinine
• urea is likely low due to reduced blood flow as a result of reduced blood volume due to water loss
  
  • As such as such, the glomerular filtration rate will be lower due to reduced blood pressure - less urea will be filtered into urine and serum urea will be higher
  • creatinine is the same - would noromally be filtered into the kidneys - but because blood volume is low, glomerular filtraion will be low and creatinine will remain in serum
• there are a few Potassium is primarily an intracellular ion
  
  • Infections or irritation of the intestine can perturb ion transport, or cause cellular leakage due to cell death - and thus reduced potassium

Question 14

State procedures to reduce GI infection

Answer 14

• Aseptic technique
• Hand washing (alcohol gel not sufficient for prevention of viral transmission)
• Cleaning of patient wards
• Toilet cleaning
• appropriate regimens for food hygeine - important for transfer of food bourne toxins
• Educatoin of patients for good hygeine
• Patient isolation in single rooms/low pressure rooms

Question 15

Endotoxins are capable of perturbing normal electrolyte secretion. Name examples of organisms that perturb chloride secretion, causing it be expelled out by the CFTR.

Answer 15

• Cholera toxin
• Heat stable enterotoxin (E.coli)

Question 16

When a compartment, say the blood, has high osmolality, what will happen to water levels in an adjacent cell?

When the blood has low osmolarity - what way will way water move?

Answer 16

• Move into blood
• Move into cell

Question 17

Name diseases that can cause secretory diarrhoea?

Answer 17

Carcinoid syndrome

Zollinger-Ellison syndrome

Question 18

Compare diarrhoea volumes between secretory and inflammatory diarrhoea

Answer 18

Secretory: High volume

Inflammatory: Low volume

Question 19

Is potassium mostly found inside or outside cells?

Answer 19

INSIDE

Question 20

Summarise the differences between tonicity and osomlality

Answer 20

Osmolality - The amount of solute per kilogram. A solution with low osmolality has fewer solute particles per kg of solution, while a solution with high osmolarity has more solute particles per kg of solution.

Tonicity - Way of comparing two solutes by their number of non-penetrating solutes; and thus the resulting water shift.

If the cell has a higher initial concentration of nonpenetrating solutes than the solution, at equilibrium water will have moved into the cell. The solution is hypotonic to the cell.

• 

If the solution has a higher initial concentration of nonpenetrating solutes than the cell, at equilibrium water will have moved out of the cell. The solution is hypertonic to the cell.

• 

If the cell and solution have equal concentrations of nonpenetrating solutes, at equilibrium there will be no net movement of water. The solution is isotonic to the cell.

Freely penetrating solutes in a solution can be ignored for the purpose of determining tonicity. They will contribute to the osmolarity of the solution but distribute throughout the cell-solution system as if the cell membrane were not present. They, therefore, do not ultimately contribute to water movement between compartments.

Urea is the classic example of a penetrating solute. It freely crosses most cell membranes, especially the erythrocyte membrane, via diffusion through urea transporters and (to a small degree) through the phospholipid bilayer (10). NaCl is the primary nonpenetrating solute of the ECF. Its ions carry a charge, making it difficult for them to freely pass through the phospholipid bilayer of the cell membrane. As noted later, while some Na+ does leak into cells, Na+-K+-ATPases pump Na+ out at roughly the same rate, making this solute functionally impermeable.

Solution B has 200 mosM NaCl compared with the cell’s nonpenetrating solutes at 300 mosM. The nonpenetrating solute concentration is higher in the cell, so water moves into the cell until the nonpenetrating solute concentrations are equal. Water movement into the cell increases the cell volume at equilibrium, making solution B hypotonic to the cell.

So although both solutions have an osmolarity of 500 mosM and are hyperosmotic to the cell, hypotonic solution B exerts a greater effect on the volume of the cell at equilibrium than isotonic solution A.

This example shows how a hyperosmotic solution can be isotonic or hypotonic, depending on the concentration of nonpenetrating solutes in the solution. Saying “a cell will ultimately shrink after being placed in a hyperosmotic solution” is not always correct, although this is frequently heard in the classroom. A cell will shrink when placed in a hypertonic solution. This example is useful for showing students that, while osmolarity and tonicity are related, they are not the same thing.

whilst penetrating solutions affect final osmolarity, they do not contribute towards tonicity.

Question 21

Name important factors to consider when look at speed of fluid replacmenta

Answer 21

Age

renal function

cardiovascular status

How much time it took for dehyrdation to develop

Severity of dehydration

Question 22

Colloids are a type of IV solutin with relatively large molecular weight, that remain in the vascular circulation. How do they work? Give common things you would find in colloids?

Answer 22

• They basically exert a high oncotic pressure, essentially creating a water deficit
• This drives water from the interstital space into the blood - thereby expanding blood volume and increasing blood pressure
• Expand blood more volume for volume compared to crystalloids.
• Albumin,gelatin and dextran solutions, hydroxyethyl starches (HES).

Question 23

Crystalloids are solutions containing electrolyte and nonelectrolyte solutes capable of entering all body fluid compartments The major disadvantage of crystalloid solutions is their limited ability to remain within the plasma because the capillary wall is highly permeable to both water and small ions. Give examples of solutions that are crystalloids?

Answer 23

0. 9 Saline
1. 45 Saline

Dextrose

Sodium bicarbonate

Ringer’s lactate

Hartman’s solution

Question 24

The osmolarity of plasma is approximately 265-295 mmol/kg.

Answer 24

• Something that is hypoosmolar will always be hypotonic - causing cell swelling.

Dextrose although can freely can pass into cells - it is quickly metabolised inside cells, and cannot leave. As a result water would enter cells, and cause them to swell - thus is hypotonic. You could in theory give a hyperosmotic dextrose solution but it would still be hypotonic.

Question 25

What is the standard postoperative regimen of fluids?

Answer 25

Saline and dextrose 2:1

Question 26

Ringer’s lactate and hartman’s both contain lactate. Under what metabolic imbalance would these be useful for? (note both of these also contain potassium).

Answer 26

Metabolic acidosis - since lactate metabolism produces lots of bicarbonate.

Ringer’s lactate can cause cerebral oedema.

Question 27

Saline 0.9 is used to replace fluids and electrolyes. It is ?????? with blood concentrations. It is given to inrease the amount of fluid and sodium when they have been depleted.

Answer 27

Isoosmotic

Question 28

5% dextrose is hypotonic- since the dexrtose will travel into the cells. The dextrose will be metabolised into ??? and ???????. This fluid is only used when ????? replacement is required, and there are no ????? loses.

Answer 28

• Water and carbon dioxide
• water
• ion

Question 29

It is usual to give 500ml bags of IV fluids, given usually every 2 hours, 4 hours, 6 hours or 8 hours (6L,3L,2L or 1.5L/daily). 6l is for emergency rehydration, with 6 hours being ore standard. 8l is considered slow rehydration.

The minimum potassium loss each day is about 60-80mmol per day (40-60 in urine, 10 in stool and 10 in skin). In order to replace daily loses, 60-80 of potassium must be given daily and intravenously if there is no oral intake. If the paitent is ???????, then more must be given per day. 20mmol of potassium cholride can be manually added to a 500ml bag of fluid. It can be unsafe to give more than ???mmol of KCL per hour, ???mmol of KCL per litre of fluid, and ???mmol of KCL per day.

Answer 29

Hypokalemic

20mmol

40mmol

140mmol.

Question 30

Low magnesium can affect levels of which other ion?

Answer 30

Potassium and calcium

Question 31

Potassium disturbances cause arythmias. Study the differences in ECG

Question 32

https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323595636000124#hl0000397

Really nice source for overview of ion absorption in the GIT.