Intestinal Fluid Balance,

Electrolyte and Fluid losses in

diarrhea
Debby Gates RD(SA)
BSc Dietetics (US)
2 Military Hospital
Department of Paediatrics
Wynberg
GTSDEB002@myuct.ac.za
Outline
1. Fluid absorption & secretion 5. Dehydration
- signs / symptoms
2. Regulation of the osmotic
- types
gradient - consequences

6. Rehydration
3. Mechanisms of Diarrhea
7. Nutritional consequences of
4. Secretory and osmotic diarrhea diarrhea
 Background
Extracellular fluid (ECF) - ⅓ of total body water
Body = 60% fluid (plasma & interstitial fluid)
2 Compartments Water moves passively between fluid
Intracellular fluid (ICF) - ⅔ of body water compartments = in response to
osmotic gradient.
Water shifts across membrane to area
with higher solute [ ] / from diluted to
ECF
concentrated solution = osmosis
Low concentration
High concentration

Cell membrane
Na-K-
ATPase
pump
ICF

Water passes through

Electrolytes cannot move through fluid compartments as water. permeable cell membrane
Rely on transport channels: from area of [low solute]
to area of [high solute]
Passive: along chemical / electrical gradient.
Active: against gradient.
 Intestinal fluid balance
Intestinal fluid balance

A. Absorption of water & B. Secretion of fluids and

electrolytes from digested food electrolytes into intestine (glands
(intestinal villi) of bowel epithelium)

Fluid absorption > fluid secretion Net result : fluid absorption

Osmotic gradient

Disruption in balance = diarrhea or constipation

Fluid absorption & secretion
• GIT Secretions = 7-8L
• Intake = 1-2L
9L

• Absorbed
- small intestine = 7800ml
- large intestine = 1250ml

• Excreted = 100-200ml
Fluid absorption and secretion
• Daily bi-directional flux of 8-9 L H20 between
intestinal lumen and blood
• Osmotic gradient
• H2O and e- simultaneously secreted in crypts and High concentration

absorbed in villi
• Maintains nutrients in solution
• Dilutes hypertonic intestinal contents

• AIM: Absorption > secretion

crypts
• Reduced absorption or increased secretion
 Maintenance of Osmotic Gradient
Absorption of water from GI tract = via osmosis…..

In response to an Osmotic gradient

Maintained by 2 processes:

A. Increased luminal osmotic B. Movement of Electrolytes

pressure (load) due to influx
and digestion of foodstuff
 Maintenance of osmotic gradient
A. Increased luminal osmotic pressure resulting from influx
and digestion of foodstuffs

• Ingestion (starch/protein/fat) large molecules enter GIT

not hypertonic

• Eg. Starch digested to sucrose, fructose (large molecule becomes many

smaller molecules)

• Now hypertonic increases osmotic load water drawn into GIT

lumen and dilutes content for further digestion

• After absorption of maltose / glucose / amino acids

reduced osmotic load and water drawn back into cells
Intestinal absorption of water
Dilute chyme Creation of Hypertonic chyme
enters lumen isotonic chyme enters lumen

Water crosses intestinal

H2O membrane by osmosis
H2O

As ions and nutrients absorbed, iso-osmotic equivalent of water

“follows” almost instantaneously through intercellular pores
 Maintenance of osmotic gradient
B. Movement of electrolytes
Water movement primarily operated by active absorption of electrolytes, especially sodium.
Na+ & Cl- & K +
• Complex physiological and biochemical functions
• Maintain ionic and osmotic balance

Absorption Carbohydrate & Protein

Important to maintain balance
Water balance
Electrolytes move across cell membranes:
• Passive: along chemical / electrical gradient
• Active: against gradient Na-K-ATPase-pump important to maintain gradient
 Maintenance of osmotic gradient

• 20-30 g sodium (and Cl⁻ / HC03⁻ / H⁺) secreted daily in intestinal secretions

• Dietary sodium 2- 5 g daily

• Continuous secretion and absorption in small intestine – mostly absorbed and

VERY small amounts lost in feces

• Diarrhea excessive secretion or reduced absorption can result in rapid

sodium depletion
Movement of electrolytes
Extracellular space

Plasma
membrane

Intracellular space / Cytoplasm

 Movement of electrolytes
Luminal Basolateral
membrane membrane
Extracellular space Active
Lumen transport
system

[Na⁺] = ↑
lumen [Na⁺] = ↑ ECF
Intracellular space / [Na⁺] = ↓ ICF
Cytoplasm
Driving force
for facilitated
Epithelial cell transporters
 Movement of Electrolytes
• ↓ [Na⁺] in enterocyte + ↑ [Na⁺] in lumen = osmotic gradient
• Na⁺ absorbed from GIT

• Process also important to move other molecules

• Digested food (glucose / amino acids) enters cell via a

secondary active transport system -- facilitated by sodium

Na⁺-dependent-glucose-transporter
Sodium/Glucose cotransporter 1(SGLT 1)
 Movement of electrolytes
• Transfer of Na⁺ to extracellular fluid --- raises osmolality
• Na⁺ absorbed into cell & facilitates glucose entry
• cell osmolality -- Water moves into cell
• extracellular [Na⁺] = water diffuses
+
Na
• Active removal of Na⁺ from
cell drives further diffusion
of Na⁺ from lumen into cell H2O

Glucose
Amino
acid
K+ Na+
Glucose
Na+
H + ATP
 Movement of electrolytes
• Transport of Na⁺ ions into cell (across jejunal epithelium) more + charge.
• Lumen more neg charge due to Cl⁻ = sets up electrical charge gradient.
• Chloride ions move by diffusion along electro-chemical gradient.

Chyme relatively Basal epithelium

electronegative relatively electropositive

Cl- Cl-
Cl- Na+
Na+ Na+ Na+

Cl- Na+ Na+

Cl-
 Summary
Na-K-ATPase pump
Cl- Na+ into
cell via o
smotic g
radient
Cl-

Cl-
X2
Glu & a/acids into cell
via SGLT 1
Cl-

X3
Cl-

Cl- into cell via electro-chemical gradient

 In Ileum and colon
• Cl- absorbed by active transport in exchange for equivalent
number of bicarbonate ions
Na+
H2O bicarb
• HCO3- neutralizes acidic products of bacterial action in the
colon

•Each HCO3- carries 1x Na⁺ Cl-

•NaHCO3 carry iso-osmotic equivalent of water into colon

Chloride-bicarbonate exchange system disrupted by various
lumen
bacterial toxins -- cause diarrhea – life-threatening.
 Chloride secretion
• Crypt cells of small intestine actively secrete lumen
electrolytes, leading to water secretion
• Cl⁻ enters crypt cell: co-transport with Na⁺
& K⁺
• Activation Adenylyl cyclase →cAMP
→CFTR= Cl- into lumen
• Cl⁻ attracts Na⁺ →NaCl
• Water drawn into lumen via osmosis
CFTR: C-AMP chloride channel (cystic
fibrosis trans-membrane conductance
regulator)
 Chloride secretion
• Abnormal activation of cAMP-dependent chloride channel (CFTR)
• Severe life-threatening diarrhoea
• Several bacterial toxins activate adenylyl cyclase in crypt enterocytes

lumen
• Elevated levels cAMP
• Chloride channels stuck in the
“open position”
• Ongoing movement of Cl into lumen
• Increased osmolarity
• Massive secretion of water (diarrhoea)

• Eg: cholera
 Mechanisms of diarrhoea
The basic process which incomplete absorption
causes diarrheal disease of water from lumen

Usually secretion & absorption occurs simultaneously with absorption being

greater

↑ Absorption / ↓ secretion excess water in lumen DIARRHEA

Therefore diarrhea is condition of altered water and electrolyte transport

 Mechanisms of diarrhea
Secretions Osmotic • Motility • Structural
Inflammation balance • Medication • Functional
Secretory Osmotic • Food allergy or • Genetic
diarrhea diarrhea intolerance

Watery diarrhea

Intestinal infection can cause diarrhea via both mechanisms

Secretory is more common
Both may occur at the same time in an individual
 Secretory diarrhea
• Disordered / disrupted epithelial electrolyte transport
– caused by toxin activating a pathway (or inflammatory processes / (infectious)
medication / genetic disorders)

• Results from ingestion of poorly absorbed / unabsorbed

substance (ions or sugars) that draws water from plasma into
lumen
 Secretory diarrhea

Cl− channels in the apical membrane of enterocytes

1. Activation Cystic fibrosis transmembrane conductance regulator
Ca2+-activated Cl− channels
Increased or continued
Increased fluid secretion into lumen secretion of chloride from
crypts into lumen
AND / OR

2. Inhibition Na+ transport Impaired or inadequate

absorption of sodium by villi

Reduced fluid absorption from lumen

 Secretory diarrhea
Na+
Cl-
Decreased
absorption of Na⁺

Loss of water and

electrolytes as watery stool

Dehydration H2O

Continues during fasting

Increased secretion of Cl⁻
 Secretory diarrhea

Toxins (most common in developing countries)

• Bacteria - Cholera
- Escherichia coli
- Shigella
- Salmonella
- Campylobacter
• Viruses - Rota (most common cause of severe diarrhea in infants, children & elderly)
• Parasites - Entamoeba histolytica
- Cryptosporidium parvum
 Osmotic diarrhoea
• Bowel mucosa allows rapid osmotic flow of water and ions to maintain
osmotic balance between lumen and plasma

• Excessive amounts of osmotically active particles (ions & nutrients) in

lumen
• Far exceeds needed increased luminal pressure / load

• more fluid moves into the bowel lumen along the osmotic gradient
• poor ability to re-absorb water (ongoing load) & electrolytes
• watery stools dehydration
Osmotic diarrhoea
Osmotically active substance ingested and poorly absorbed:

• Unabsorbed solutes
• fructose, lactose, sugar alcohols (eg xylitol), artificial sweeteners
(aspartame / saccharine), MCTs, etc

• Osmotic laxatives
• Lactulose, poly-ethylene-glycol (PEG)

• Antibiotics, chemotherapy, radiotherapy

 Dehydration
Signs of dehydration – Infants & children
Blood gas (biochemical):
Capillary refill less than 2 seconds pH
Dry mucus membranes HCO3⁻
Absence of tears Na⁺
Sunken fontanelle Base-excess
PCO2
General ill appearance Osmolality

Mild: no hemodynamic changes; ± 5%

Rehydration source, route &
Moderate: tachycardia; ± 10%
volume depends on extent & type
Severe: hypotension + impaired perfusion
of dehydration
(circulatory compromised); ± 15%
 Dehydration
Signs of dehydration – Adults
Mild to moderate Severe
Increased thirst Severely decreased urine output or no
Dry mouth urine output (deep yellow / amber color.
Sleepy Dizziness or lightheadedness - cannot stand
Reduced urine output; concentrated or walk normally
Headache Low blood pressure
Dry skin Rapid heart rate
Dizziness Fever
Poor skin elasticity
Lethargy, confusion, or coma
Rehydration source, route & volume Seizure
depends on extent & type of dehydration
Shock
Dehydration

Identify types of dehydration

Isotonic Hypertonic (Hypernatremic) Hypotonic (Hyponatremic )

 Types of dehydration
Isotonic dehydration (~80% of cases): Type most often caused by diarrhoea

Biochemical features: Clinical manifestations:

Loss of Na and H2O • Thirst

in same proportion as
• Balanced deficit of sodium and water • Sunken fontanelle, lack of tears,
normally found in ECF
• Normal serum [Na]: 130-145 mmol/l • Dry mucous membranes
• Normal serum osmolality: 275 -295 mOsm/l • Reduced skin turgor, sunken eyes
• Hypovolaemia results from ECF loss • Tachycardia
• Oliguria
 Types of dehydration
Hypertonic dehydration: Sometimes occurs in children esp. infants

Loss of free H2O in excess Biochemical features: Clinical manifestations:

of Na when compared with
normal ECF

Usually from ingesting • Deficit water > Na deficit • Disproportionately severe thirst

hypertonic, poorly absorbed fluids • High serum [Na]: >150 mmol/l • Irritability
& not enough free water during • High serum osmolality: >295 mOsm/l • Seizures
diarrhea episode. Hypertonic
fluids cause movement of H2O
(osmosis) into lumen with
retention of Na within circulation.
Insufficient water intake /
excessive sweating.
 Types of dehydration
Hypotonic (Hyponatreamic) dehydration

Biochemical features: Clinical manifestations:

Loss of Na in excess of free
water. Excess H2O absorbed
from the gut while Na loss
continues.
• Deficit of sodium > H20 deficit • Lethargy
• Low serum [Na]: < 130 mmol/l • Occasionally seizures may occur
Usually when drinking large
• Low serum osmolality: < 275 mOsm/l
amounts of water or hypotonic
fluid with low NaCl content e.g.
marathon runners OR those who
receive inappropriate IV
rehydration (e.g. plain dextrose )
 Acid-Base balance
Acid-Base Balance: Acid: substance which can donate H⁺
[H⁺] in body fluids maintained within narrow range. Base: substance which can accept H⁺
Crucial for normal cellular activities.

Serum pH: 7,36 – 7,41

↑ plasma [H⁺] → ↓ pH (more acidic) Acidosis = ↑ acid in body fluid

Metabolic (or Respiratory)
Serum HCO3:
• DKA - ↑ ketones (acid) in body fluid
• Hyperchloremic acidosis – ↑ loss
NaHCO3 – during severe diarrhea
Base-deficit acidosis (metabolic)
Large amounts of intestinal Hypovolaemia from
bicarb lost in diarrhoea dehydration = poor renal
perfusion (poor renal
resorption of bicarb)

Base deficit and acidosis

develops rapidly

Hypovolaemic shock adds to acidosis through lactate

production in under-perfused tissue

Features:
• Low serum bicarbonate, may be <10mmol/l
• Low arterial pH, may be <7.10
• Kussmaul’s breathing
• Increased vomiting
Other losses
• Large faecal losses cause
depletion of:
• Potassium (greatest in infants) Signs of K+ depletion:
• Particularly dangerous in the
malnourished who are often • Generalized muscle
deficient in K+ before diarrhoea. weakness
• Acidosis: ↓ K may be masked as • Cardiac arrhythmia
K+ moves from ICF to ECF in
exchange for H+. • Paralytic ileus
• Rebound hypokalaemia when
acidosis corrected without giving K+
Oral rehydration
• Sodium-glucose transporter (SGLT1) is not necessarily affected by
microbes or inflammation in gut
• If Na and glucose are present in lumen the SGLT1 continues to work,
even when Cl channels continue to cause secretion.
• Oral rehydration solutions (ORS) with both Na and glucose in correct
proportions = increased absorption of Na = increased passive water
absorption
• ORS will not stop the diarrhea, but absorption of water and solutes
will exceed secretion and prevent dehydration
 Oral rehydration
• Oral rehydration solution appropriate for mild to moderate diarrhea except
most severe cases
• life-threatening dehydration, paralytic ileus, unable to drink, profuse vomiting, very
rapid stool loss
• ORS hugely successful to reduce childhood mortality

• Appropriate solutions:
• Isotonic with plasma (300mOsm/l)
• MUST contain sodium
• MUST contain sugar in a 1:1 ratio with sodium to facilitate sodium absorption
• Ideally should contain some potassium and a base: citrate or bicarbonate
Rehydration
Which fluids?
• Appropriate “home” fluids: breastmilk, infant formula, sugar-salt
solution, salted cereal gruels, salted legume soups
• Appropriate IV fluids: Ringer’s Lactate, Normal saline + KCl, Half
Darrow’s, Half Normal saline + 10% glucose + KCl
• UNACCEPTABLE FLUIDS: Plain IV or oral glucose/dextrose, commercial
soups, undiluted soft drinks or cool-drinks
• HOME ORS FORMULA
• In 1 litre (no less) of clean boiled and cooled tap water add: To achieve correct
osmolarity
• ½ level teaspoon salt (NO MORE)
• 8 level teaspoons sugar (NO MORE)
Oral rehydration solution
Composition of standard and reduced osmolarity ORS solutions

  Standard ORS solution Reduced Osmolarity ORS solutions

  (mEq or mmol/l) (mEq or (mEq or (mEq or

mmol/l) mmol/l)
mmol/l)
Glucose 111 111 75-90 75
Sodium 90 50 60-70 75
Chloride 80 40 60-70 65
Potassium 20 20 20 20
Citrate 10 30 10 10
Osmolarity 311 251 210-260 245
 Role of Zinc
• Reduces volume and duration.
• Reduces re-occurance
• Effective even in individuals who are not Zn-depleted
• Side effect: vomiting

• Oral supplementation:
• 10 – 14 days
• 20 mg/d - older than 6 months
• 10 mg/d - younger than 6 months (WHO)
Diarrhea and nutritional status
Diarrhea may cause a decline in nutritional status including weight loss

• Reduced dietary intake

• Vomiting, loss of appetite, withholding of food

• Decreased nutrient absorption

• Damage to villi, deficiency of brush border enzymes, loss of bile salts, rapid gut transit

• Increased nutritional requirements

• Fever, illness, repair to gut mucosa, replacing of lost protein (sloughed mucosa and exuded
plasma proteins)
the end
References

• Biochemical, Physiological and Molecular aspects of nutrition. Stipanuk

& Caudill. 3rd edition, 2013. Chapters 34 – 35 (selected pages on Vula)

• Krause’s Food and the Nutrition Care Process. Mahan, Escott-Stump &
Raymond. 14th Edition, 2016. Chapters 6, 28

• A Whyte & H R Jenkins. Pathophysiology of diarrhoea (2012).

Paediatrics And Child Health 22:10
 References
Books
• Biochemical, Physiological and Molecular aspects of nutrition. Stipanuk &
Caudill. 3rd edition, 2013. Chapters 34 – 35 (selected pages on Vula)
• Krause’s Food and the Nutrition Care Process. Mahan, Escott-Stump &
Raymond. 14th Edition, 2016. Chapters 6, 28
 References
Journal articles
• Dhingra, U., Kisenge, R., Sudfeld, C. R., Dhingra, P., Somji, S., Dutta, A., Bakari, M., Deb, S., Devi, P.,
Liu, E., Chauhan, A., Kumar, J., Semwal, O. P., Aboud, S., Bahl, R., Ashorn, P., Simon, J., Duggan, C. P.,
Sazawal, S., & Manji, K. (2020). Lower-Dose Zinc for Childhood Diarrhea - A Randomized,
Multicenter Trial. The New England journal of medicine, 383(13), 1231–1241.
https://doi.org/10.1056/NEJMoa1915905
• Keely, S. J., & Barrett, K. E. (2022). Intestinal secretory mechanisms and diarrhea. American Journal
of Physiology-Gastrointestinal and Liver Physiology. https://doi.org/GI-00316-2021
• Sweetser S. Evaluating the patient with diarrhea: a case-based approach. Mayo Clin Proc. 2012
Jun;87(6):596-602. doi: 10.1016/j.mayocp.2012.02.015. PMID: 22677080; PMCID: PMC3538472.
• Thiagarajah JR, Donowitz M, Verkman AS. Secretory diarrhoea: mechanisms and emerging
therapies. Nat Rev Gastroenterol Hepatol. 2015 Aug;12(8):446-57. doi: 10.1038/nrgastro.2015.111.
Epub 2015 Jun 30. PMID: 26122478; PMCID: PMC4786374.
• Whyte, L., & Jenkins, H. (2012). Pathophysiology of diarrhoea. Paediatrics and Child
Health, 22(10), 443-447. https://doi.org/10.1016/j.paed.2012.05.006
questions
Contact details
• Debby Gates, RD(SA)
GTSDEB@myuct.ac.za

• Dr Janetta Harbron, PhD, RD(SA)

Jannetta.harbron@uct.ac.za