Factor VII deficiency
pH 7.4 PCO2
B. Ulcer Formation
Plate6.7UlcerII
159 Bile salts,
pancreatic enzymes O2 radicals
Stress (shock, burns, operation)
Gastritis
Psychogenic components
Barrier function disturbed
H+ secretion Pepsinogen secretion
Chemical aggression Prostaglandin
synthesis Indomethacin, diclofenac,
acetylsalicylic acid, etc.
Helicobacter pylori infection
Gastrinoma, Smoking etc.
Ulcer Rapid restitution
through migration
Blood perfusion Mucosal
protection
Epithelial damage
Granulation, angiogenesis, restitution of basal membrane Covering defect
through cell division Wound
Smoking
Smoking
Wound healing Smoking
Radiograph: Treichel J. Doppelkontrastuntersuchung des Magens, 2nd ed. Stuttgart: Thieme; 1990
Disorders after Stomach Surgery
Gastric tumors are treated surgically by remov-ing the stomach (gastrectomy [GE]) and replac-ing it with jejunal loops, or by gastric resection (Billroth I or II, or Roux). Treatment-resistant gastric ulcers have also been treated with selec-tive vagotomy (VT). Nonselecselec-tive VT is often unavoidable in tumor operations or when bleeding occurs. These procedures may result in undesirable functional disorders (→A):
Surgical reduction of gastric volume and disordered accommodation reflex and recep-tive relaxation reflexes after VT increase gas-tric wall tension when ingesting a normal meal; this leads to feeling full, nausea, and vom-iting as well as premature satiety. A serious consequence is too rapid gastric emptying.
This is due to: 1) an absent accommodation re-flex that raises the pressure gradient from stomach to small intestine; 2) the “apportion-ing” antrum and pylorus are absent; and 3) gastric emptying into the small intestine is no longer inhibited. The latter is especially true af-ter VT (no vagovagal reflex) and in gastric re-section after Billroth II or Roux, in which chyme circumvents the duodenal chemosensors.
Consequences of too rapid gastric emptying are (→A, bottom):
◆Too high a chyme volume per unit time dis-tends the intestinal wall and, via hormones and neurotransmitters, brings about nausea, vomit-ing, cramps, and pain as well as vasomotor reac-tions with cutaneous vascular dilation (flush), tachycardia, palpitations, and abnormal ortho-static regulation. This early dumping syndrome (occurring 30–60 min after food intake) is also in part due to:
◆Hypertonicity of chyme that is emptied too quickly. Via osmotically obliged water secretion into the intestinal lumen, this chyme also: 1) increases intestinal distension; 2) results in di-arrhea; and 3) leads to further cardiovascular reactions that are initiated by the resulting hy-povolemia.
◆Furthermore, the secreted water dilutes the enzymes and bile salts in the intestinal lumen.
This dilution can be critical, for example, for the liberation of heme-iron from hemoglobin in food or for absorption of fat including the fat-soluble vitamin D (see below).
◆High concentrations of carbohydrate and
es-pecially sugar (e.g., marmalade) in chyme also cause symptoms because the rapid absorption of glucose causes a high hyperglycemia peak that 90–180 minutes after food intake fol-lowed by reactive hypoglycemia due to the re-lease of insulin (confusion, loss of conscious-ness), the so-called late dumping syndrome.
◆Rapid gastric emptying also exceeds the di-gestive capacity of the upper small intestine.
Moreover, after VT pancreatic secretion is de-creased to half, and in Billroth II the upper du-odenum does not receive the flow of chyme, so that there is no physiological stimulus for se-cretin and CCK secretions. As a result, the distal small intestine takes part in the digestion and absorption of nutrients. Its chemosensors are intensively involved in initiating reflexes and hormonal signals that bring about the feeling of premature satiety (see above), so that these patients eat too little and lose weight. Deficient chyme preparation is partly responsible for the distal shift of digestion and absorption. After distal gastric resection, the pieces of food leav-ing the stomach are too large (> 2 mm). As one third of iron in food comes from hemoglobin (in meat), incomplete digestion of oversized food particles diminishes the availability of heme-iron.
Billroth II (but not Roux-Y) gastrectomy can lead to the blind loop syndrome (→pp. 38 and 164).
Reduced H+secretion in the stomach de-creases the liberation of iron in food and the absorption of Fe(II). Loss of the sources of iron will ultimately lead to iron-deficiency anemia (→p. 42).
Additionally, when the number and activity of the parietal cells is diminished, the secretion of intrinsic factor is also reduced. If it falls be-low 10 % of its normal value, cobalamin absorp-tion is affected so that (long-term) cobalamin deficiency can arise and the anemia is further aggravated (→ p. 38). Osteomalacia will ulti-mately result from Ca2+and vitamin D deficien-cy (→p. 144).
160
6Stomach,Intestines,Liver
Plate6.8DisordersAfterStomachSurgery
161 Vomiting,
pain Flushing,
tachycardia
Late dumping syndrome
Emptying Preparation
of chyme Gastric
secretion Pancreatic
secretion
Glucose
absorption Intestinal
distension Water
secretion Digestion moved distally
Hypo-volemia Dilution of enzymes and
bile salts
3060min after meal
90180 min after meal:
clouding of consciousness Billroth I operation
Billroth II operation
Vagotomy (VT)
Heme-Fe availability distensionWall
Selective Unselective
Gastric resection
Gastric
volume Accommod-ation reflex
Sugar Volume Hypertonicchyme Nutrients Meat
FeII salts
Weight loss Osteomalacia Anemia intakeFood Vitamin D deficiency Cobalamine
deficiency Fe deficiency
deficiencyIF Fat absorption
Premature satiety
Ca2+
Diarrhea Vasomotor
reactions
Hyper-glycemia
Reactive hypo-glycemia
Gastrectomy Replacement stomach
Early dumping syndrome
FeII absorption A. Disorders After Stomach Surgery
Diarrhea
The term diarrhea is used if stool has lost its normal firm consistency. This is usually associ-ated with an increase in its weight (in males > 235; in females > 175 g/d) and its fre-quency (> 2 per day). Diarrhea can have various causes:
Osmotic diarrhea results from the intake of a large number of substances that are not or only slowly absorbable even normally, or in mal-absorption (→p. 164 ff.). Among the first group are sorbitol (in“sugar-free” medications and sweets or certain fruits), fructose (in lemon-ades, diverse fruits, honey), magnesium salts (antacids, laxatives) as well as poorly absorbed anions such as sulfate, phosphate, or citrate.
Nonabsorbed substances are osmotically ac-tive in the small intestine and therefore“suck”
water into the lumen. (H2O secretion; →B, left). Table A illustrates this in a simulated ex-periment. Intake of, for example, 150 mmol of a nonabsorbable substance (in this example, polyethylene glycol, PEG) in 250 mL water (PEG concentration = [PEG] = 600 mmol/L) starts os-motic water secretion in the duodenum so that the volume is increased to 750 mL ([PEG] falls to 200 mmol/L). The osmolality has adjusted to that of plasma (290 mOsm/L), 90 mOsm/L now being contributed by Na+, K+and the accompa-nying anions (ion secretion into the lumen be-cause of the high chemical gradients). The vol-ume in the middle of the small intestine has ris-en to 1000 mL. [PEG] has fallris-en to 150 mmol/L, and the entering ions contribute 140 mOsm/L.
Because of the high active absorption, especial-ly of Na+(plus anions–) in ileum and colon (denser epithelium than in the jejunum), the osmolality contributed by the ions falls to 90 and 40 mOsm/L, respectively. The main cation in stool is K+(marked Na+absorption in ileum and colon). The result is that given 150 mmol PEG in 250 mL H2O, the volume of diarrhea will be 600 mL. Without ion absorption in the ileum and colon (e.g., after resection, disease), the vol-ume of diarrhea could even rise to 1000 mL.
(PEG is, e.g., given to cleanse the gut before a coloscopy).
In malabsorption of carbohydrates (→B, right and p. 164 ff.) the reduced Na+absorption in the upper small intestine (diminished Na+ symport with glucose and galactose) leads to
reduced water absorption. The osmotic activity of the nonabsorbed carbohydrates additionally results in water secretion. However, bacteria in the large intestine can metabolize up to 80 g/d (divided over four meals) of nonabsorbed car-bohydrates into organic acids useful for provid-ing energy that together with water are ab-sorbed in the colon (→B, middle). It is only the large amounts of marked gas produced (flatu-lence) that provide evidence of carbohydrate malabsorption. However, if > 80 g/d (i.e., > ¼ of normal carbohydrate supply) is not absorbed or the intestinal bacteria are decimated by antibiotics, diarrhea occurs.
Secretory diarrhea (in the narrow sense) oc-curs when Cl–secretion of the small intestinal mucosa is activated (→C). Within the mucosal cells Cl–is secondarily actively enriched by a basolateral Na+-K+-2 Cl–symport carrier and is secreted via luminal Cl–channels. These open more frequently when the intracellular con-centration of cAMP rises. cAMP is formed in greater amounts in the presence of, for exam-ple, certain laxatives and bacterial toxins (Clos-tridium difficile, Vibrio cholerae). Cholera toxin causes massive diarrhea (up to 1000 mL/h) that can rapidly become life-threatening because of the loss of water, K+, and HCO3–(hypovolemic shock, hypokalemia, nonrespiratory acidosis).
Overproduction of VIP (vasoactive intestinal peptide) by pancreatic islet cell tumors also causes high cAMP levels in intestinal mucosa cells leading to copious, life threatening diar-rhea: pancreatic“cholera” or watery diarrhea syndrome.
There are several reasons why diarrhea oc-curs after resection of the ileum and of part of the colon (→D). Bile salts, normally absorbed in the ileum, cause accelerated passage through the colon (reduced water absorption). In addi-tion, the nonabsorbed bile salts are dehydroxy-lated by the bacteria in the colon. The resulting bile salt metabolites stimulate the secretion of NaCl and H2O in the colon. Finally, there is also a lack of active absorption of Na+in the resected intestinal segments.
162
6Stomach,Intestines,Liver
Plate6.9Diarrhea
163 H2O
(mL) 250 750 1000
750 600
(mmol)PEG
150 150 150 150 150
[PEG]
(mmol/L) 600 200 150 200 250
[Na+]+[ K+] (mmol/L)
~0 45 70 45 20
[Anions]
(mmol/L)
~0 45 70 45 20
Osmol.
(mosm/L) 600 290 290 290 290 Uptake of 150mmol of a nonabsorbable,
osmotically active substance (PEG) in 250mLH2O
Secretion of H+O+Na2+(+anions+K)
Absorption of H2O+Na+, secretion of K+
(after K.D. Fine et al.)
Hormones and neurotransmitters
(e.g. VIP)
Toxins (cholera, clostridium
difficile) Laxatives
Diarrhea
cAMP
Small intestine epithelium NaK++ Na+
Cl 2Cl
Cl channel
Resection of ileum and parts of colon
Bile salt reabsorption
Accelerated passage through colon
Colon bacteria Bile salt metabolites NaCl and H2O secretion Diarrhea
Water absorption No Na+ absorption from resected segments
Osmotic
diarrhea Flatulence Secretory diarrhea Poorly absorbed
carbohydrates (e.g. sorbitol, fructose)
Disorder of carbohydrate digestion and absorption (e.g.disaccharidase deficiency,carrierdefects)
Na+ cotransport
Na+ absorption
H2O absorption H2O secretion in
upper small intestine
Carbohydrates max. 34 g/h
Short-chain fatty acids Gases (H2,CO2) Antibiotics
Bacteria
Large intestine
Injejunum
H2O
Cl H2O