Pathophysiology of gastro-intestinal tract

Gastro-intestinal tract
Organs of oral cavity
Esophagus
Stomach
Small and large intestine
Secretory function of salivary glands, liver, pancreas
Neurohormonal regulation

Major processes in GIT
nutrition
digestion, absorption
movement
Salivary glands
absorption
Vena cava
rectum
stomach
esophagus
Colon
intestine
secretion
digestion
motility

Physiology of the stomach
пищевод
дно
Pyloric sphincter
двенадцатиперстная
кишка
антральный
отдел
(секреция слизи,
пепсиногена,
гастрина)
isthmus
Parietal cells
Smooth muscle
cells
G-cells
Chief cells
cells
тело
(секреция слизи,
пепсиногена, HCl)

Antral G-cell
Parietal cell
Gastrin
Н+
secretion
К+,H+ АТФase
CNS
Acetylcholine
Antral receptor
Local reflex
Histamine
Acetylcholine
Stretch
Parietal receptor
Food (view, smell, test)
Regulation of gastric secretion

Mechanisms of gastric
hypersecretion
Stimulation:
neurogenic (vagotonia),
hormonal (gastrin, histamine, ↑Ca2+ in hyperparathyroidism…)
Failure of inhibitory mechanisms (antral, duodenal)
Hyperplasia of the gastric glands

Gastrinoma (Zollinger-Ellison syndrome)
Marked gastric hypersecretion
Diarrhea
Abdominal pain
Peptic ulcer(s) of upper GI tract
Gastro-esophageal reflux
Gastrin-secreting tumor of the duodenum (75%), pancreas (24%), stomach, liver, ovary (1%).

Pathogenic consequences of gastric hypersecretion
Disorders of gastric motility (hypercontraction)
Disorders of digestion
Hyperkinesia
Disorders of water-electrolyte and acid-base balance
Development of acid-dependent diseases
Erosion
Acute ulcer
Chronic ulcer
mucosa
Submucous layer
Muscle layer
Serous

mucus
bicarbonate
PG Е2
Adequate blood flow
HCl
pepsin
Bile acids
Helicobacter рylori
agressive
Aggressive and protective factors of gastric juice
amylin
protective

Helicobacter pylori

The role of
Helicobacter pylori
Helicobacter pylori
urease
urea
ammonia
Increase of pH
in antrum
Gastrin production
Hyperproduction of
НСl
Increase of
IFNγ , TNFα
apoptosis, slowing of regeneration and reparation
Antral gastritis B, ulcer
Risk of cancer
Cytiotoxic
effect
cytotoxines
(Vac A, Cag A…)
Injury of
epithelium
Infiltration with
neutrophils

Ulceroprotective effect
of amylin
Inhibition of gastric secretion
Stimulation of production of mucus
Acceleration of healing of mucosa

Pathogenesis of gastro-esophageal
reflux disease (GERD)
Motor dysfunction of the
lower esophageal sphincter
Gastro-esophageal
reflux
Decreased mucosal resistance
Increase in
intragastric
pressure
Decreased esophageal clearance
Gravity
Esophageal peristaltics
Saliva
Renewal of the epithelium

Mechanisms of gastric hyposecretion
Disorders of regulation
(neurogenic, hormonal)
Atrophy of mucosa (autoimmune gastritis)
Resection of the stomach

Induction of autoimunity against parietal cells

Mechanisms of immune-mediated parietal cell death leading to gastric atrophy

Complications of gastric hyposecretion
Disorders of protein digestion
Hypokinesia
Disorders in barrier function
Disorders of iron and vitamin В12 absorption
Disorders of intestinal secretion and digestion

Increased gastric motility (gastric hyperkinesia)
Neurogenic
Increased production of НСl, gastrin, motilin …
Hypercalcemia
Pylorostenosis
Complications:
Decrease volume adaptation
Increase in intragastric pressure
Increased tone of the stomach
Dyspepsia

Decrease of gastric motility
Neurogenic
- reflex gastroparesis
- authonomic neuropathy (diabetes, alcoholism) - vagotomia
Humoral
- hyposecretion of НCL
- increased production of HCl, GIP, amylin…
Disorders of smooth muscle cell metabolism
- anorexia
- chronic intoxication
- hypokalemia
- ischemia

The passage of chyme through GI tract in normal conditions (A) and after resection of stomach (B)
A
B

The consequences of stomach resection
Disorders in reservoir function of the stomach
Decreased number of secretory cells (achlorhydria)
Vitamin B12 deficiency → anemia
Disturbance of fractional influx of chyme into the duodenum
Disturbances in the regulation of secretory function of pancreas and liver
Accelerated passage of chyme through the small intestine