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Aspek Biokimia Fungsi

Absorpsi dan Sekresi Intestinalserta Hubungannya dengan

Patofisiologi Diare

Bagian Biokimia Kedokteran

Fakultas Kedokteran

Universitas Islam Sumatera Utara

2012

Normally, absorption and secretion ofwater and electrolytes occur throughoutthe intestine.

Water and electrolytes are simultaneouslyabsorbed by the villi and secreted by thecrypts of the bowel epithelium.

A healthy adult takes in less than 2 litres of

fluid each day. Saliva and secretions fromthe stomach, pancreas, and liver addabout 7 litres, making a total of about9 litres that enter the small intestine everyday.


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Only 100 to 200 mL of water being

excreted each day in formed stools.

When net secretion exceeds its limitedabsorptive capacity, diarrhoea occurs.

When solutes (particularly sodium/Na) areactively absorbed Osmotic gradientsare created Absorption of water fromthe small intestine

To enter the epithelial cells, sodium is :

a. Linkedto the absorption of chloride,

b.Absorbed directly as sodium ion,

c. Exchanged for hydrogen ion,

d. Linked to the absorption of organic

materials (monosaccharide, AA).


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Glucose

Galactose

Fructose


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After being absorbed, sodium is

transported out of the epithelial cells by

an ion pump referred to as Na+K+ATPase Na to ECF Osmolality

Waterand other electrolytes to flow

passively from the bowel lumen through

intercellular channels and into the ECF.

ECF : Extracellular fluid

ICF : Intracellular fluid

IS : Interstitial fluid

Secretory stimuli increase the ability of

chloride to pass through the luminal

membrane of the crypt cells, allowing that

ion to enter the bowel lumen

This movement of chloride ion creates an

osmotic gradient that causes water and

other electrolytes to flow passively from

the ECF into the bowel lumen through the

intercellular channels.


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Compounds that stimulate active

secretion and inhibit active absorption:

a) Neurotransmitters: Vasoactive intestinal peptide (VIP)

Acetylcholine

Substance P

ATP and UTP

b) Serotonin and Neurotensin.

Released by enterochromaffin cells

c) Prostaglandins, leukotrienes and platelet-

activating factor (PAF).

Released by inflammatory cells.

(d) Guanylin, a luminally active peptide

released by Goblet cells.

The Ca2+ increase opens a basolateral K+

channel different from that opened by

cAMP.

VIP and acetylcholine are the

predominant transmitters with direct

epithelial secretory and/or antiabsorptive

effects released by secreto-motor nerves.


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The group of compounds that both inhibit

active secretion (HCO3 as well as Cl) and

enhance active absorption, includesnorepinephrine (via 2-receptors),

neuropeptide Y, enkephalins, all

neurotransmitter, and somatostatin.

Norepinephrine, the predominant

antisecretory/proabsorptive agonist in the

intestines, activates 2-receptors on both

enterocytes (22) and nerves (S32, S33). Theneural effect is inhibitory, blocking release of

secretion-inducing neurotransmitters.

PATHOPHYSIOLOGY OF DIARRHEA

General Aspects

Patients may use the word diarrhea for

increases in stool mass (in adults, up to

250 g/dL is considered normal), stool

liquidity, or stool frequency. The first

criterion truly defines diarrhea.
http://www.ncbi.nlm.nih.gov/pubmed/6278952http://www.ncbi.nlm.nih.gov/pubmed/6278952


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Diarrheal driving forces

Osmosis, active secretion, exudation,

and altered motility diarrhea.

Osmotic Diarrhea :

When poorly absorbable, lowmolecular

weight aqueous solutes are ingested, their

osmotic force quickly pulls water and,

secondarily, ions into the intestinal lumen.Such as : Lactulose, sorbitol or Mg2+.

Osmotic diarrhea can also develop when anordinarily absorbable nutrient is ingested by an

individual with an absorptive defect.

Eg. Lactose intolerence congenital lactase

deficiency, or carbohydrate by someone with

gluten-sensitive enteropathy (celiac disease),

maldigestion in pancreatic insufficiency.

Secretory Diarrhea :

Diarrhea resulting from overstimulation of the

intestinal tracts secretory capacity can develop

in pure form (e.g., cholera) or as a component

of a more complex disease process (e.g., celiac

disease, Crohn disease).


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Pure secretory diarrhea is characterized by :

a.Large stool volumes (which can exceed 1 liter per

hour in well hydrated adults),

b.Absence of red or white blood cells in the stool,

c.Absence of fever or other systemic symptoms

(except those due to dehydration),

d.Persistence of diarrhea with fasting (volume may

diminish).

A number of secretory stimuli can cause

diarrhea, These include bacterial enterotoxins,

hormones generated by endocrine neoplasms,dihydroxy bile acids, hydroxylated fatty acids, &

inflammatory mediators.

Exudative diarrhea :

If the intestinal epitheliums barrier function

is compromised by loss of epithelial cells or

disruption of tight junctions, hydrostatic pressure

in blood vessels & lymphatics will cause water

and electrolytes, mucus, protein, and sometimes

even red and white cells to accumulate luminally

(e.g., ulcerative colitis, shigellosis, intestinal

lymphangiectasia).


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1

PATOPHYSIOLOGY OF ACUTE

DIARRHEAS

Enteric infection with enterotoxin-producing

bacteria

Three bacterial enterotoxins produced by two

enteric organisms, V. cholerae and E. coli.

In fact, similar toxic peptides are produced by

Yersinia (S52), Salmonella (S53) and perhaps

other enteropathogenic bacteria,

The V. cholerae enterotoxin, is an 84-kDa

protein, consisting of a dimeric A subunit and

5 identical B subunits.

Toxigenic E. coli Travelers diarrheaElaborate at least two secretion-

stimulating enterotoxins : 1) Heat-labile

toxin and 2) Heat-stable toxin, activates

guanylate cyclase in the intestinal

epithelium , thereby activating cGMP-

dependent protein kinase (PKG), which,

like PKA, can open the CFTR anionchannel.


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Enterotoxin attach to endocrine

(enterochromaffin) cells on the villus

surface of the intestinal epithel, causing anincrease of cAMP or cGMP release

serotonin, neurotensin, and possibly other

peptides (eg. VIP) into the subepithelial

space.

The VIP attaches to receptors on both villusand crypt enterocytes, activating adenylylcyclase and inducing cAMP-mediatedalterations of ion transport (inhibition ofabsorption in villus cells and stimulation ofsecretion in crypt cells).

Common bacterial causes of enteritis and/orcolitis are Shigella, Salmonella,Yersinia,enteroinvasive E. coli, P. aeromonas, andCampylobacter.

These organisms invade the epithelium andmultiply intracellularly, damaging the surfaceepithelium and causing inflammation (releaseinflamatory mediator ) Diarrhea.

Some viruses also invade the intestinalepithelium, causing enterocyte destruction,inflammation, and a temporary sprue-likesyndrome (partial villus atrophy and crypthypertrophy).


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These include rotavirus (worldwide, probably

the most common cause of diarrhea in

infants), certain adenoviruses.

Some enteric bacteria produce cytolytic

toxins that destroy epithelial cells, interfering

with absorption and causing inflammation.

These include : Shigella dysenteriae

(Shiga toxin), a protein synthesis inhibitor;

Clostridium difficile, (A toxin, alters

cytoskeletal structure), and whoseproliferation is induced by broad-spectrum

antibiotics; Vibrio parahaemolyticus.

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