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Pathophysiology of digestion MD, Prof. Yu.I. Bondarenko. Insufficiency of digestion. The reasons . Manifestations.
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Pathophysiology of digestion MD, Prof. Yu.I. Bondarenko
Insufficiency of digestion. The reasons. Manifestations • The basic role of digestive system consists in digestion of components of food that enter into an alimentary canal (proteins, fats, carbohydrates), absorption of formed nutrients and removing from an organism end-products of metabolism. • Numerous functions of digestive system are regulated by the central and autonomic nervous system, humoral and endocrine influences. • Disorders of regulation cause disturbance of normal course of the processes in an alimentary canal, result in insufficiency of digestion and promote development of many diseases.
Insufficiency of digestion • It is pathological condition at which the digestive system does not provide assimilation of the nutrients that enter in the organism. • hereditary insufficiency of digestion (some kinds malabsorption) • acquired insufficiency of digestion
Causes of digestion insufficiency development • 1. Alimentary (food) factors: • a) reception of bad and rough food • b) dry rations • c) irregular reception of food • d) disbalanced meal (for example, reduction of the contain of vitamins, proteins in diet) • e) abuse in alcohol • 2. Physical factors • Greatest role belonge to radiation which damage epithelial cells of the alimentary channel which have high mitotic activity
3. Chemical agents: Poisonings with inorganic and organic compounds. • 4. Biological factors: • a) bacterium (for example, v.cholera, dysentery, typhoid, paratyphoid fever) • b) bacterial toxins (for example, salmonellosis, staphylococcus infection) • c) viruses (for example, adenoviruses) • d) helminths • 5. Organic effects: • a) congenital anomalies of digestive system • b) postoperative conditions • c) tumors of digestive system
6. Disorders of nervous and humoral regulation: • a) psychoemotional disorders (neurotic and neurosis-like conditions) • b) mental diseases (schizophrenia, maniac - depressive syndrome) • c) organic diseases of the central nervous system (encephalites) • d) lesions of peripheral structures of autonomal nervous system • e) reflex disorder (various viscero-visceral reflexes) • Disorders of humoral regulation of digestion may be connected to disorders of synthesis and secretion gastrointestinal hormones (gastrine, secretin, cholecystokinin-pancreazymin etc.)
Insufficiency of digestion may manifests syndromes: • 1. Starvation • 2. Dispeptic syndrome • 3. Dehydratation • 4. Disturbance of the acid-base balance • 5. Intestinal autointoxication • 6. Painful syndrome
DISPEPTIC SYNDROME • Dispeptic syndrome includes different combinations of the following symptoms: • a) anorexia • b) heartburn • c) eructation • d) nausea • e) vomitting • f) meteorism • g) constipations • h) diarrhea
ANOREXIA Anorexia is a full absence of appetite while person need food Kinds of the anorexia: • а) intoxical - develops during acute and chronic poisonings (for example, salts of mercury, medical products, bacterial toxins) • b) dispeptic - arises at diseases of digestive system, has more often behavior-reflex nature • c) neurodynamic - develops as a result reciprocal disturbance of the appetite centre after overexcitation of structures limbic systems (for example, painful syndrome during heart attacks, colics, peritonitis)
ANOREXIA • d) neurotic - is connected with excessive excitation of cortex brain and strong emotions (especialy negative) • e) psychogenic – is connected with conscious restriction of food (for example, with an aim of getting thin or as result of mental disorders) • f) neuroendocrinopathy - is caused by organic lesion of the central nervous system (hypothalamus) and endocrine diseases (hypophysial cachexia, Addison’s disease)
Mechanisms of anorexia development : • 1. Reduction of excitability of the food centre (intoxical, dispeptic, neuroendocrinopathy anorexia) • 2. Inhibition of neurons of the food centre (neurodynamic, neurotic, psychogenic anorexia)
The heartburn is a feeling of heat or burnings long esophagus. • Development is connected with irritation of receptors of esophagus during pelting contents of stomach into one (reflux). • It may be caused by: • а) increase forming of gastric juice • b) functional insufficiency of cardial sphincter
The eructation is sudden involuntary allocation into oral cavity some gas from a stomach or a gullet, sometimes with small portions of contents of a stomach • The increasing of the contents of gases in stomach may be caused by two reasons: • а) receipt big quantity of gases with food and a drink (for example, aerated drinks), siping of air (aerofagia) • b) formation of gases in the stomach, it is especial at a long delay there peep (at a stomach ulcer, cancer of a stomach) • As a result of increasing of the contents of gases in a stomach it is increased intrastomach pressure. It reflexly can cause: • а) reduction of muscles of a stomach wall • b) a spasm of the gatekeeper • c) a relaxation of muscles of aesophagal-gastric sphincter • Thereof gases are superseded from a cavity of a stomach in a gullet, to a drink. And then in an oral cavity
The nausea is a burdensome sensation in epigastric area breast and in the oral cavities, quite often previous to vomitting and frequently accompanying with the general weakness, sweatness, increasing of salivation, coldness of arms and legs, pallor of a skin, decrease of arterial pressure that is connected to activation parasympathic nervous system. In a basis of a nausea is an excitation of the emetic centre, but insufficient for occurrence of vomitting lays. • Vomitting - the complex-reflex act which results to eruption of contents of a stomach outside through a mouth is a result of excitation of the emetic centre which is situated in an oblong brain.
The mechanism of vomitting includes a number of consecutive stages. His pick out the following pathogenetic variants of vomitting: • а) central - it is connected with increasing of excitability of the emetic centre. It happens at diseases of the central nervous system (meningitises, encephalities, tumours of a brain), at excitation of cortex of the big hemispheres (behavior-reflex vomitting) or receptors of a labyrinth (vestibular vomitting); • b) hematogenic-toxic - it is caused by direct action of toxic substances which are in blood, on receptors that are in emetic centre. It may be exogenous substances (carbonic oxide, alcohol, medical products, toxins of bacteria) or toxic products of an own metabolism which are collected during at a uremia, hepatic insufficiency, decompensated diabetes and others; • c) visceral (reflex) – is a result of reflexes which are caused from different receptors of internal organs. Such reflexogenic zones are in a stomach, a mucous membrane of pharynx, coronal vessels, peritoneum, biliary duct etc.
Meteorism is a superfluous accumulation of gases in the digestive channel due to their increased formation or insufficient removing from intestines • Superfluous formation of gases underlies development of the following kinds of meteorism: • а) alimentary - develops at reception with food a lot cellulose, starches (leguminous, cabbage, a potato) • b) disorders of digestion (pathology of enzymes, disturbances of absorbtion, intestinal disbacterioses)
Disturbance of discharge of gases typically for such meteorism: • а) mechanical - develops as a result of Disturbance of passableness of intestines (spasms, solderings, tumours) • b) dynamic - arises at disorders of motor function of intestines • c) circular – is a result of the general and local disorders of blood circulation
It is pick out two mechanisms of development of constipations - spastic and atonic. • The first is caused by long constant reduction of smooth muscles of guts, the second – because of their atonia. • To spastic constipations concern: • а) inflammatory - arise owing to local spastic reflexes with changed of mucous membrane; • b) proctogenic - develop at a pathology anorectal areas; • c) mechanical - arise at impassability of guts; • d) toxic – is result of poisonings lead, mercury, thallium.
Atonic constipations are: • а) alimentary - develop at receipt light food containing(not enough) cellulose • b) neurogenic – is the result of disorders of nervous regulation of a motility of guts • c) hypodynamic - arise at bed patients, at old men, people with very low motor activity • d) constipations at anomalies of a thick gut (Girshprungs disease) • e) constipations in consequensce disorders water-electrolyte metabolism
Diarrhea • Pathogenetic variants of diarrheas: • а) osmotic diarrhea. Develops when osmotic pressure is increase because of intestinal contents at intake of substances which are bad or are not absorbed at all (for example, laxative), and also at disturbances of digestion and absorbtion (syndromes maldigestion and malabsorbtion) • b) secretory diarrhea. It is connected with activation of secretion of ions (Na+ , Cl‾), that causes the strengthened secretion of water into gap of guts (for example, during cholera) • c) diarrhea, caused by braking of active transport of ions through cellular membranes in guts (for example, congenital chlordiarrhea - genetic defect of absorbtion of anions of chlorine in illeum) • d) diarrhea is caused by increase of permeability of an intestinal wall (inflammatory) • e) diarrhea at disturbance of an intestinal motility
Intestinal autointoxication, as a rule, is connected with infringement corelation between bacterias and formation a plenty of toxic products of fermentation and putrafaction. • Dysbacteriosisis an infringement of a ratio between separate kinds of microflora. Thus the quantity of the bacteria causing processes of putrafaction and fermentation is frequently increased. As a result formation in guts of toxic products - hydrogen sulphide, scatol, indole, phenols, putrescine, cadaverine grows etc. If formation of these products exceeds functional ability of a liver on them detoxifcation, attributes of hepatic insufficiency develop. Development of intestinal autointoxication is promoted by reduction of intestinal peristalsis(constipations), reduction of secretion of intestinal juice, intestinal obstruction.
PAIN • The pain frequently accompanies with development of diseases of the alimentary channel. Depending to the reasons and pathogenesis pain may have different characters. • Distinguish the following mechanisms of occurrence of pain at lesions of digestive organs: • The spastic mechanism. The pain is caused by a spasm of smooth muscles of different parts of the alimentary channel. In this case the reason of pain is constriction of the vessels which are located in the wall of hollow organs owing to that the ischemia develops. It cause appearance of metabolism products in the working organs, and their influence on pain receptors. At sharply arising strong spasm pain on colics type develops
PAIN • The hypotonic mechanism. At reduction of smooth muscles tone (hypotonia) the pain appears due to stretching the wall of hollow organs ( stomach, guts, gall bladder) by their contents. Thus the mechanical stretching of tissues causes irritation of the nervous endings; • Influence of biological active substances (histamine, serotonin, kinines, prostaglandins) on the nervous endings. These substances are formed and secreted at damage of cells and inflammation (gastritis, duodenitis, enteritis, colitis, cholecystitis). Especially a lot of these substances appear during acute pancreatitis.
Functional disorders of digestive system • 1. Disturbance of digestive system secretion : • а) hypersecretion states: • 1 hypersalivation • 2 gastric hypersecretion • 3 pancreatic hypersecretion • 4 hypercholia • b) hyposecretion states: • 1 hyposalivation • 2 gastric hyposecretion • 3 pancreatic hyposecretion • 4 acholia
2. Disturbance of motor function of the alimentary channel: • 1 disturbance of chewing • 2 disturbances of swallowing - dysphagia • 3 gastric dyskinesia • 4 intestinal dyskinesia • 5 dyskinesia of gall bladder and biliary ducts • 6 disturbances of defecation • 3. Disturbance of digestive and absorptive functions - syndromes of maldigestion and malabsorption.
Hydrochloric acid, pepsin, mucus secretion disturbance • Hydrochloric acid is secreted with parietal cells of mucous membrane of stomach. Their number in the healthy person is about 1 billion. • Phases of secretion: 1.Neurogenic (vagal); 2.Gastric (gastrine); 3.Intestinal that is regulated by intestinal hormones. • In regulation of functional activity of parietal cells takes place nervous system (through mediator acethylcholine), and also various hormones (serotonin, insulin). The parietal cell contains receptors to histamine which is released from enterochromaphilic cells (ECL), gastrin and cholecystokinin (CCK-receptors), and also receptors for acethylcholine (M3-receptors),
REGULATION OF OUTPUT HCL • Stimulation of H2-histamine receptors is bring on formation cAMP, and stimulation of CCK-receptors and M3-receptors results to increasing of level of endocellular calcium (Са++). • Stimulation of M3-receptors increases, not only total Са++ into cell and due to increasing of level inositolthreephosphate (IP3) strengthens an output of endocellular Са++. • Gastrin, cholecystokinin and histamine also raise output of Са++ due to action on IPh3 . • Parietal cell has receptor to prostaglandin E2 (PGE2)) which stimulation reduces level cAMP and results ihibition of hydrochloric acid secretion. • Secretion of hydrochloric acid by parietal cell is carried out by principle of the proton pump in which K+ exchanges on H+, and Cl-‾ on HCO3-‾. An important role in this process plays H+, K+ -ATPase which, using energy of ATP, provides transport H+ from parietal cells and K+ into cell.
Hypersecretion of hydrochloric acid plays the important role in development of several gastroenterologic illness, may be observed at hereditary conditioned increasing of weight parietal cells, the increased tone of a vagal nerve, stretching of antral part of stomach during disorder of emptying, increasing of secretion of gastrin, increasing quantity of ECL-cells in the mucous membrane of stomach (in the patients with carcinoid syndrome). • The main cells of mucous membrane form pepsin . It is know seven types of pepsinogen. Disturbance of pepsin formation take place in the number gastroenterologic diseases (for example, stomach ulcer).
Gastric mucus is secreted by stomach mucous cells. Into structure of gastric musous contain glycosaminoglycans and glycoproteins. • From sialic acids N-acethylneuraminic acidprovides ability of gastric mucus to form water-insoluble viscose lay of stomach mucus membrane. • Stimulating influence on formation of mucus result irritation of adreno- and cholinoreceptors, prostaglandins. Hydrolysis of lisosoms cause dehydratation of glycoproteins. • Gastric mucus (together with bicarbonates) takes part in formation of mucus barrier which supports a gradient рН between hollow of stomach and its mucus membrane and H+. • Disturbance of this barrier as a result of reduction the synthesis of prostaglandins in the wall of stomach.
Gastric hypersecretion is characterized : • Increased quantity of gastric juice as after reception of food and also on the empty stomach • Hyperaciditas and hyperchlorhydria - is increase of the common acidity and the maintenance of free hydrochloric acid of gastric juice • Increasing of digestive ability of gastric juice
The disturbances of digestion connected with gastric hypersecretion, are caused with long delay food in the stomach (pylorus is closed, because neutralization of very acidic contents that goes into duodenum,it take a lot time). • Consequences: • A little contents that enter into guts lead to reduction of gut peristaltic and constipation development. • Processes of fermentation and formation gases is amplified in the stomach. It causes appearance of eructation and heartburn • Motor activity of stomach is increased as a result hypertone and hyperkinesis of smooth muscles.
Gastric hyposecretion is characterized: • Reduction the quantity of gastric juice on an empty stomach and after reception of food • Decreased or zero acidity of gastric juice (hypo-or unacidity), reduction of the contents in it or absence of the free hydrochloric acid (hypo- or achlorhydria) • Reduction of digesting ability of gastric juice due to achylia (the full stop formation a hydrochloric acid and enzymes)
Reduction of gastric secretion stipulated disturbance of digestion along alimentary channel. • Insufficient formation of gastric juice that keeps pylorus opened also contents of stomach quickly passes into duodenum where environment becomes constantly alkaline. It causes inhibition of formation secretin. • Insufficiently digested components of food irritate receptors of mucus membrane of guts that results in their strengthening of peristaltic and diarrhea develop. • Besides an absence of a hydrochloric acid leads to development of microflora in the stomach. • Activation of processes of rotting and fermentation is connected appearance such disturbance of digestion, as an eructation, the impose tongue etc.
Disturbance of stomach motor function Disturbance of stomach motor function is called gastric diskinesia • Trere are two kinds of gastric diskinesia: hypertonic and hypotonic • Hypertonic kindis characterized strengthening of peristaltic(hyperkinesia) and increasing of stomach muscles tone (hypertonia) • The hypotonic kind, on the contrary, is characterized hypotonia and hypokinesia
The reasons of motor gastric disturbance of hypertonic type • Some food factors (rough food, alcohol) • Increase of gastric secretion • Increase of vagal nerve tone • Some gastrointestinal hormones (motilin) Hypertension and hyperkinesia of stomach leads to: • A long time delay of food in stomach that promotes increase of gastric secretion and development of ulcers of mucus membrane • Development antiperistaltic of stomach that results in development of dispeptic disturbances (an eructation, nausea, vomitting)
One forms of diskinesia of stomach hypertonic type is pylorospasm • It is observed mainly in babies, especially in the first weeks and months of life. • Pylorospasm in children is caused by functional disturbances of the nervous- muscular system of pylorus part stomach. It is observed mainly at the excitable children who have transferred intra-uterine hypoxia, born in asphyxia with attributes of a birth trauma of the central nervous system • At pylorospasmis marked weak development of muscles in cardial parts of stomach and its more expressed development in the area of pylorus. It promotes development of vomitting and eructation
Causes of stomach motor activity reduction • Alimentary factors (fat food) • Reduction of gastric secretion (hypoacidic gastritis) • Reduction of vagal nerve tone • Action gastrointerstitial hormones (gastroinhibiting peptide, secretine etc.) • Removal of stomach pylorus • The common weakening of organism, an exhaustion, gastroptosis At hypotonic diskinesia time of staying of food in the stomach is shortened that lead to disturbance of its digestion. Action undigested components of food on receptors of mucus membrane of guts causes increase of peristaltic and diarrhea.
ETIOLOGY OF GASTRIC ULCER • Etiology ofulcer disease now is not established ! • In development of stomach and duodenal ulcers • take place the following risk factors • 1. Psychoemotional negative overstrains (negative emotions, conflict situations, feeling of constant alarm, overfatigue etc.) • 2. Stress • 3. Hereditary predisposition • 4. Nutritional disorder – live on dry ration, irregular reception of nutriment, eating of rough or pungent food, bad chawing of food, fast meal, absence of the teeth, the insufficient contents in food of proteins and vitamins • 5. Chronic gastritis and duodenitis with increased secretion • 6.The microbic factor - Helicobacter pylori • 7. Harmful habits - smoking, abuse of alcohol
Pathogenesis of stomach ulcer in general is reduced to disturbance of balance between factors acid-peptic aggressions of gastric contents and elements of protection of stomach mucus membrane and duodenum. • Sufficient of bicarbonates buffer, good regeneration of epithelial cells, blood supply of mucus membrane, normal formation of prostaglandins in wall of stomach are factors that protect mucus. • Helicobacter pylori. These bacterias produce a lot of enzymes (urease, protease, phospholipase), damaging protective barrier of mucus membrane, and also various cytotoxins. The most pathogenic are Vac A-strains, that produce vacuolizing cytotoxin which results in formation cytoplasmatic vacuoles and destructions of epithelial cells, and the Sad A-strains which express gene associated with cytotoxin. This gene codes protein which has direct damaging effect on mucus membrane. • Helicobacter pylori promotes liberation in a mucus membrane of stomach interleukines, lisosomal enzymes, TNFα, that causes development of inflammatory processes in mucus.
