Wake Gi Diarrhea, Fluid And Electrolyte Absorption

Front 1

Diarrhea

Back 1

is not a disease , it is a pathology in response to a condition

results from an imbalance

Excessive loss of water in
the feces (> 300 ml/day)

(Clinically defined as > 3 bowel movements/day)

Front 2

Absorption
(Definition)

Back 2

The transfer of substances from the lumen of the gastrointestinal tract into the circulation (net absorption)

Front 3

Efficient Absorption of any substance depends on...

Back 3

Adequate form (digestion products)

Adequate surface area for absorption

Adequate rate of transit through the intestine

Specific cofactors and/or carriers

Front 4

Osmolality
(Definition)

Back 4

Osmoles of solute per kg of solvent (depends on the number of particles in solution)

Front 5

What is the osmolality of the plasma?

Back 5

Luminal contents of the intestine are isotonic compared with plasma
(~290 mOsmols/kg)

Front 6

Site of Absorption

Back 6

Minimal in the stomach and colon, primarily in the small intestine

Front 7

Why is the small intestine so good at absorption?

Back 7

Structural Configuration of the
Small Intestine (Structure aids function)

The efficiency of absorption is increased by increasing the available surface area at 3 levels of magnitude

The intestinal mucosal surface area is under trophic influences linked to the presence of food in the gastrointestinal tract

Front 8

How much do the circular folds of the small intestine increase the surface area of the intestinal cylinder?

Back 8

3 fold

Front 9

How much do the circular villi of the small intestine increase the surface area of the intestinal cylinder?

Back 9

30 fold
(another 10 fold over circular fold)

Front 10

How much do the microvilli of the small intestine increase the surface area of the intestinal cylinder?

Back 10

600 fold
(another 20 fold over villi)

Front 11

What are the basic components of the small intestine and how do they facilitate absorption?

Back 11

1) Small intestinal surface area
is amplified by the circular folds, villi, & microvilli.

2) Absorption is also facilitated by movement of the villi. This stirs the chyme immediately adjacent to the mucosa and presents new surfaces
for absorption. Movement of the villi is regulated by local nervous reflexes and hormonal mechanisms.

3) Extension of the microvilli is
regulated to facilitate absorption by increasing surface area.

Front 12

Blood flow to Villus at rest

Back 12

Rate of blood flow to the small intestine is
about 10-15% of Cardiac output (75%-> mucosa,
5%->submucosa, 20%->muscularis externa)

Front 13

Blood flow to villus after a meal

Back 13

Blood flow increases 30-130% (especially to
the mucosa) as a result of increased fraction
of Cardiac output going to the small intestine
as well as shunting of blood from other layers
to the mucosa

Front 14

What is the postprandial blood flow to intestine

Back 14

1-2 liters/minute

Front 15

How much fluid is endogenously secreted in one day? Components?

Back 15

7000 ml/day

bile= 500 ml/day

pancrease = 1500 ml/day

salivary glands =1500 ml/day

stomach = 2500 ml/day

Front 16

What is oral intake/day?

Back 16

2000 ml/day

Front 17

What percent is absorbed of the orally intaken substances and endogenous secretions?

Back 17

98%

Front 18

What is the most important organ for quantitative water absorption occur?

Back 18

jejunum

Front 19

What is the most efficient organ of water absorption?

Back 19

colon

Front 20

Cellular Mechanisms of Water Absorptions

Back 20

Water absorption is passive and dependent on absorption
of ions (principally Na+ & Cl-) and solutes (sugars, amino acids)

Water movement may be transcellular (through the cell) or paracellular (through the tight junctions between cells)

Water moves bidirectionally to keep the luminal contents isotonic with plasma

BIDIRECTIONAL, PASSIVE, FOLLOWING OSMOLES

Front 21

Where is passive solute permeability the best?

Back 21

Passive solute permeability and water absorption decreases caudally.
(Highest permeability in duodenum/jejunum)

this is why the jejunum is most important for quantitative absorption of water

the colon has very tight, tight junctions (therefore, the worst)

Front 22

Ion Transport in the

Jejunum

Back 22

Na: Actively absorbed (enhanced by absorption of sugars, amino acids)

K: Passively absorbed

Cl: Passively Absorbed

HCO3: Secreted

Front 23

Ion Transport in the

Ileum

Back 23

Na: Actively absorbed

K: Passively absorbed

Cl: Absorbed (exchanged for HCO3)

HCO3: Secreted

Front 24

Ion Transport in the

Colon

Back 24

Na: (ENAC is important)

K: Net secretion (when luminal [K]<25 mM)

Cl: Absorbed (exchanged for HCO3)

HCO3: Secreted

Front 25

What is the importance of K+ Absorption?

Back 25

*Most K+ absorption in the small intestine is driven by water absorption, that increases the lumenal K+ concentration.

Hence, significant K+ loss may occur in diarrhea, leading to decreased extracellular levels and life-threatening consequences such as CARDIAC ARRHYTHMIAS.

Infants with prolonged diarrhea are particularly susceptible to HYPOKALEMIA.

There is not a good active mechanism for reabsorbing the K+.

Front 26

Basic Principles of Water Absorption

Back 26

Water movement in the intestine is passive & dependent upon transport of electrolytes and other solutes

Water movement may be transcellular or paracellular (through the tight junctions between cells)

Water moves bidirectionally to keep the luminal contents isotonic with plasma

Ions (& solutes) are transported via transcellular and paracellular pathways into the lateral spaces, where
a “standing osmotic gradient” is established for the
passive movement of water.

Front 27

GI effects of Opiods

Back 27

Constipation...although with withdrawal - diarrhea

Front 28

Compounds released by enteric neurons that stimulate net secretion

Back 28

Acetylcholine
Nitric oxide
Serotonin
VIP
Substance P

Front 29

Compounds released by enteric neurons that promote net absorption

Back 29

Norepinephrine
Neuropeptide Y
Opioids

Front 30

Compounds released by enteroendocrine cells in mucosa or submucosa that stimulate net secretion

Back 30

Histamine
Calcitonin
Guanylin
Bradykinin
Platlet-activating factor
Prostaglandins
Leukotrienes
Arachidonic acid
Adenosine

(inflammatory mediators)

Front 31

Compounds released by enteroendocrine cells in mucosa or submucosa that promote net absorption

Back 31

Somatostatin

Front 32

Hormones (via the circulation) that stimulate net secretion

Back 32

Prostaglandins
Atrial natriuretic peptide
Gastrin
Motilin
Bombesin
GIP

Front 33

Hormones (via the circulation) that promote net absorption

Back 33

Epinephrine
Enkephalins
Aldosterone
Glucocorticoids
Angiotensin II
Peptide YY
Prolactin
Growth hormone

Front 34

Lumenal factors that stimulate net secretion

Back 34

Bile salts
Long-chain fatty acids

Front 35

Lumenal factors that promote net absorption

Back 35

Short chain fatty acids

Front 36

Osmotic Diarrhea

Back 36

Presence of osmotically active nonabsorbable luminal contents
(e.g., magnesium salts, lactose, lactulose, sorbitol, etc.)

Front 37

Exudative Diarrhea

Back 37

Loss of epithelial cells or disruption of tight junctions allows water and electrolytes to accumulate in the lumen (e.g. ulcerative colitis, shigellosis, drugs, radiation, immune destruction – e.g. celiac disease)

Front 38

Secretory Diarrhea

Back 38

Excess water secretion into the intestine (e.g., infection, cholera, bacterial enterotoxins, endocrine tumors, drugs)

Front 39

Diarrhea associated with Motility Disturbances

Back 39

Both increases and decreases in gut motility can lead to diarrhea.

Increased motility: e.g. thyrotoxicosis, opiate withdrawal.

Decreased motility: e.g. large diverticula, smooth muscle damage associated with scleroderma, dematomyositis, amyloidosis, & muscular dystrophy; autonomic neuropathy associated with Diabetes. This diarrhea is secondary to bacterial overgrowth (bacteria disrupt electrolyte absorption and secrete osmotically active substances).

Front 40

Mechanism of Osmotic Diarrhea

Back 40

Poorly absorbed, low molecular weight aqueous solutes create an osmotic force that quickly pulls water (and ions) into the intestinal lumen (in order to maintain an intra-luminal osmolality equal to that of body fluids). Shows an abnormal Osmotic Gap (disappears with fasting)

Causes: Lactase deficiency (lactose), foods and supplements (sorbitol, lactulose, Mg++)

Front 41

Mechanims of Secretory Diarrhea

Back 41

Caused by overstimulation of the intestinal tract’s secretory capacity. Driving force is always either net secretion of Cl- or HCO3-, or inhibition of net Na+ absorption. Shows a normal Osmotic Gap.

Causes: bacterial enterotoxins, neuroendocrine tumors (overproduce pro-secretory hormones), inflammatory mediators, dihydroxy bile acids, hydroxylated fatty acids, drugs

Front 42

Mechanisms of Complex Diarrhea

Back 42

Most clinically significant diarrheas are complex, with
multiple pathophysiologic mechanisms involving consideration of paracrine,
immune, neural, and endocrine modulators

Front 43

How do you distinguish between osmotic and secretory diarrhea?

Back 43

osmotic gap

An Osmotic Gap < 50 mOsm is considered normal.
The “Gap” is normally made up of Mg2+, Ca2+, NH4+, and organic cations

Secretory Diarrhea: no excess osmotic gap in stool electrolytes, but the pattern of stool electrolytes may be altered (more common).
Osmotic Gap < 50 mOsm

Osmotic diarrhea: non-absorbable organic solutes or ions constitute a greater proportion of ions & solutes.
Osmotic Gap > 50 mOsm

Front 44

How do you determine the osmotic gap?

Back 44

osmotic gap = 290 mOsm - 2{[Na+] + [K+]}

Front 45

Mechanisms of Acute Diarrhea

Back 45

1. Enteric Infection with Enterotoxin-Producing Bacteria
2. Common bacterial causes of enteritis and/or colitis
3. Viral Causes
4. Other Causes (cryptosporidia, giardia lamblia)

Front 46

Enteric Infection with Enterotoxin-Producing Bacteria

and Acute Diarrhea

Back 46

V. Cholera (cholera toxin, CT)

Toxigenic E. coli (Heat-stable toxin, STa)

Front 47

Common bacterial causes of enteritis and/or colitis

and Acute Diarrhea

Back 47

(Damage surface epithelium, causing inflammation)

- Shigella
- Salmanella
- Yersinia
- Aeromonas
- Camylobacter
- Clostridium difficile

Front 48

Viral causes of Acute Diarrhea

Back 48

(Cause enterocyte destruction, inflammation)

- Rotovirus (Most common cause of diarrhea in infants world-wide)
- Norwalk or Norwalk-like virus

Front 49

Chronic Diarrhea

Hormone-Secreting Neoplasms

Back 49

- Pancreatic cholera (VIP)

- Carcinoid syndrome

- Medullary carcinoma of the thyroid (calcitonin)

- Zollinger-Ellison Syndrome (gastrinoma)

- Systemic Mastocytosis (H2-induced gastrin hyper-secretion)

Front 50

Chronic Diarrhea

Ileal Disease or resection

Back 50

Malabsorbed bile acids and fatty acids

Front 51

Chronic Diarrhea

Intestinal Lymphectasia

Back 51

Increased interstitial hydrostatic pressures, steatorrhea

Front 52

Chronic Diarrhea

Celiac Disease (tropical and nontropical sprue)

Back 52

Villus atrophy, inflammation

Front 53

Chronic Diarrhea

Diabetes mellitus

Back 53

Autonomic neuropathy (degeneration of adrenergic nerves)

Front 54

Chronic Diarrhea

Bacterial Overgrowth

Back 54

Bile acid and carbohydrate malabsorption

Front 55

Chronic Diarrhea

Inflammatory Bowel Disease

Back 55

Bile acid malabsorption, inflammatory mediators, bacterial overgrowth

Front 56

Medications Associtaed with Diarrhea

Back 56

1. Antacids (Mg-containing)
2. Antibiotics (most)
3. Anti-hypertensives (e.g. beta blockers)
4. Anti-inflammatory agents (e.g. NSAIDs)
5. Anti-neoplastics (many)
6. Anti-retroviral agents
7. Acid-reducing agents (e.g. histamine H2-receptor blockers, PPIs)
8. Colchicine
9. Prostaglandin analogs (e.g. misoprostol)
10. Theophylline (& caffeine- “Starbucks diarrhea”)
11. Herbal products and supplements

Front 57

Name opiates used to treat Diarrhea

Back 57

Diphenoxylate
Loperamide
Codeine
Morphine
Tincture of opium

Front 58

Name adrenergic agonists used to treat Diarrhea

Back 58

Clonidine (alpha-adrenergic agent)

Front 59

Name somatostatin analogs used to treat Diarrhea

Back 59

Octreotide (carcinoid syndrome)

Front 60

Name bile acid-binding resin used to treat Diarrhea

Back 60

Cholestyramine

Front 61

Name fiber supplements used to treat Diarrhea

Back 61

Psyllium

Calcium polycarbophil

Front 62

Nonspecific Therapies for Chronic Diarrhea

Back 62

Opiates

Adrenergic agonist

Somatostatin analog

Bile acid-binding resin

Fiber supplements

Bismuth subsalicylate (pepto-bismol)

Front 63

What changes occur in the bowel of the elderly?

Back 63

Age-related decline in CFTR expression (constipation in the elderly)

Colonic CFTR expression (Cl- secretion) declines with age (major player in water secretion)

Colonic ENaC expression (Na+ absorption) is maintained with age (major player in water absorption)

This sets up a potential imbalance between intestinal water absorption and secretion where the stool becomes excessively desiccated

Further supporting an important role of diminished Cl- secretion in constipation
is the clinical results with drugs that activate ClC2 chloride channels for the treatment of constipation.