Pathophysiology of Pathophysiology of digestion. Violation of digestion. Violation of digestion in a oral digestion in a oral cavity, stomach and cavity, stomach and intestine. intestine. Marta R. Gerasymchuk, Marta R. Gerasymchuk, M.D., Ph.D., Associate Professor of M.D., Ph.D., Associate Professor of PATHOPHYSIOLOGY DEPARTMENT, PATHOPHYSIOLOGY DEPARTMENT, Ivano-Frankivsk National Medical Ivano-Frankivsk National Medical University University
Transcript
Pathophysiology of digestion. Pathophysiology of digestion. Violation of digestion in a oral Violation of digestion in a oral cavity, stomach and intestine.cavity, stomach and intestine.
Marta R. Gerasymchuk, Marta R. Gerasymchuk, M.D., Ph.D., Associate Professor of M.D., Ph.D., Associate Professor of PATHOPHYSIOLOGY DEPARTMENT, PATHOPHYSIOLOGY DEPARTMENT, Ivano-Frankivsk National Medical Ivano-Frankivsk National Medical
UniversityUniversity
Plan of the lecturePlan of the lecture1.1. Insufficiency of digestion. Etiology.Insufficiency of digestion. Etiology.
2.2. Caries. Paradontitis.Caries. Paradontitis.
3.3. Syndromes of digestion insufficiency.Syndromes of digestion insufficiency.
4.4. Disorders of stomach.Disorders of stomach.
5.5. Ulcer disease of stomach.Ulcer disease of stomach.
ContentContentCaries. Aetiology. PathogenesisCaries. Aetiology. PathogenesisParadontitis. Aetiology. PathogenesisParadontitis. Aetiology. PathogenesisInsufficiency of Insufficiency of digestiondigestionDisturbance of stomach functions. Disturbance of stomach functions.
Disturbance of hydrochloric acid, pepsin,Disturbance of hydrochloric acid, pepsin, mucus secretionmucus secretion
Disturbance of stomach motor functionDisturbance of stomach motor functionThe reasons and pathophysiologic mechanisms of The reasons and pathophysiologic mechanisms of stomach ulcerstomach ulcerDisturbance of intestinal functionsDisturbance of intestinal functionsDisturbance of digestion and absorbtion in intestinesDisturbance of digestion and absorbtion in intestinesDisturbances of intestine motor functionDisturbances of intestine motor functionEthiology liver functions violationEthiology liver functions violationPathophysiology of the liver functions violationPathophysiology of the liver functions violationViolation of metabolic functions. Violation of antitoxic Violation of metabolic functions. Violation of antitoxic functionfunctionViolation of bile formation and excretionViolation of bile formation and excretion
ActualityActuality• Gastrointestinal disorders are not cited as the
leading cause of death in the World, nor do they receive the same publicity as heart disease and cancer.
• However, according to government reports, digestive diseases rank third in the total economic burden of illness, resulting in considerable human suffering, personal expenditures for treatment, lost working hours, and a drain on the nation’s economy.
• It has been estimated that every 3rd – 4th person in the World has digestive disease. Even more important is the fact that proper nutrition or a change in health practices could prevent or minimize many of these disorders.
Dental cariesDental caries Dental cariesDental caries is an infectious microbial
disease that begins as demineralization of inorganic portion of tooth, followed by destruction of organic portions, leading to cavity formation.
• The Caries ProcessThe Caries Process occurs as an interaction between the biofilm and the tooth surfaces: the caries lesion is the manifestation of the stage of the process at one point in time.
Salient features of carious Salient features of carious process are listed below:process are listed below:
1. Carious process is spread over time
2. Carious process does not have to progress
3. The initial lesion can be arrested and reversed
4. All ages are susceptible to caries
5. Caries is the major cause of tooth loss in all age groups. Pit and fissure caries.
AETIOLOGYAETIOLOGYFour major factors involved in aetiology:Four major factors involved in aetiology: Cariogenic bacteriaCariogenic bacteria Bacterial plaqueBacterial plaque Susceptible tooth surfaceSusceptible tooth surface Fermentable bacterial substrate (sugar)Fermentable bacterial substrate (sugar)
Classification of Caries Based on ActivityClassification of Caries Based on Activity
a. Primary caries b. Secondary caries (recurrent caries) c. Residual caries d. Arrested caries
According to World Health Organization (WHO), According to World Health Organization (WHO), thethe shape and depth of the carious lesions can be shape and depth of the carious lesions can be
scored onscored on a four-point scale (D1 to D4):a four-point scale (D1 to D4):• D1—clinically detectable enamel lesions with intact (non-cavitated surfaces)• D2—clinically detectable cavities limited to the enamel• D3—clinically detectable lesions in dentin (with and without cavitation of dentin)• D4—lesions into pulp.
Arrested caries
Spread from mandibular teeth may causeSpread from mandibular teeth may cause Spread from mandibular teeth may cause
Ludwig's angina,
parapharyngeal abscess,
mediastinitis, pericarditis,
empyema, and jugular thrombophlebitis.
Spread from maxillary teethSpread from maxillary teeth may cause purulent sinusitis,
meningitis,
brain abscess,
orbital cellulitis,
and cavernous sinus thrombosis.
It is a chronic inflammatory disease of It is a chronic inflammatory disease of the gum and tissues that surround and the gum and tissues that surround and support the teeth. If left untreated, support the teeth. If left untreated, periodontal disease can lead to tooth periodontal disease can lead to tooth loss.loss.
This disease is divided into two types: This disease is divided into two types: – Gingivitis (gum disease)Gingivitis (gum disease)– PeriodontitisPeriodontitis
What is Periodontal disease?What is Periodontal disease?
Periodontal disease (Cont.)Periodontal disease (Cont.) The development of disease is also The development of disease is also
dependent on several other factors. dependent on several other factors. – IllnessIllness
Diabetes. Many kinds of bacteria Diabetes. Many kinds of bacteria (germs) thrive on sugar, including (germs) thrive on sugar, including glucose – the sugar linked to diabetes.glucose – the sugar linked to diabetes.
– Bad habitsBad habitsSmoking make it harder for gum Smoking make it harder for gum
tissue to repair itselftissue to repair itself
– Poor oral hygiene habitsPoor oral hygiene habits– Family history of dental disease Family history of dental disease
GingivitisGingivitisThe first stage of periodontal disease.The first stage of periodontal disease.
Poor brushing and flossing habits allow Poor brushing and flossing habits allow dental plague.dental plague.
Plaque is a sticky material made of bacteria, Plaque is a sticky material made of bacteria, mucus, and food debris that develops on the mucus, and food debris that develops on the exposed parts of the teeth. exposed parts of the teeth.
If you do not remove plaque, it turns into a If you do not remove plaque, it turns into a hard deposit called tartar that becomes hard deposit called tartar that becomes trapped at the base of the tooth. trapped at the base of the tooth. Bacteria and the toxins they Bacteria and the toxins they
produce cause the gums to produce cause the gums to
become infected, swollen, and tender.become infected, swollen, and tender.
• Periodontitis – inflammation of the supporting tissue of the teeth
PeriodontitisPeriodontitis
Damages the bone and connective tissue Damages the bone and connective tissue that support the teeth.that support the teeth.
Plaque builds and hardens under the gums.Plaque builds and hardens under the gums.
The gums pull away from the teeth, forming The gums pull away from the teeth, forming “pocket” of infection.“pocket” of infection.
The infection leads to loss of the bone that The infection leads to loss of the bone that holds the tooth in its socket and might lead holds the tooth in its socket and might lead to tooth loss.to tooth loss.
Periodontal disease
A ‘two-hit’ model for the pathogenesis of A ‘two-hit’ model for the pathogenesis of accelerated periodontal destruction in patients accelerated periodontal destruction in patients
with diabetes mellituswith diabetes mellitus
Lalla, E. & Papapanou, P. N. (2011) Diabetes mellitus and periodontitis: a tale of two common interrelated diseases
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2011.106
PreventionPrevention
The best method to prevent this The best method to prevent this disease is daily brushing and flossing.disease is daily brushing and flossing.
Four steps for prevention of this Four steps for prevention of this disease are: disease are: Stop smoking. Stop smoking. Reduce stressReduce stress Maintain a wellMaintain a well- - balanced diet balanced diet
Eating foods with antioxidant properties, Eating foods with antioxidant properties, such as, those containing vitamin E or such as, those containing vitamin E or vitamin C can help your body repair vitamin C can help your body repair damaged tissue.damaged tissue.
Avoid clenching and grinding your Avoid clenching and grinding your teeth. teeth.
• Insufficiency of digestion is a pathological condition at which the digestive system does not provide assimilation of the nutrients that get inside the organism.
Etiology of digestion Etiology of digestion insufficiency:insufficiency:
1. 1. Alimentary (food) factors:Alimentary (food) factors: a) reception of bad and rough food; a) reception of bad and rough food; b) kidney live on dry rations; b) kidney live on dry rations; c) irregular reception of food; c) irregular reception of food; d) disbalanced meal (for example, reduction d) disbalanced meal (for example, reduction
of the maintenance of vitamins, proteins in a of the maintenance of vitamins, proteins in a diet); diet);
e) overindulge in alcohol.e) overindulge in alcohol. 2. 2. Physical factorsPhysical factors.. Among factors of this Among factors of this
group the greatest role belongs to radiation group the greatest role belongs to radiation which effects epithelial cells of the alimentary which effects epithelial cells of the alimentary channel which have high mitotic activity.channel which have high mitotic activity.
Etiology of digestion insufficiencyEtiology of digestion insufficiency::
3. 3. Chemical agentsChemical agents are the reason of are the reason of digestion disorders after poisonings digestion disorders after poisonings with inorganic and organic substances with inorganic and organic substances during manufacture and in life.during manufacture and in life.
4. 4. Biological factors:Biological factors: a) a) bacteriabacteria (for example, v.cholera, (for example, v.cholera,
causative agents of dysentery, typhoid causative agents of dysentery, typhoid fever, paratyphus); fever, paratyphus);
b) b) bacterial bacterial toxins (for example, at toxins (for example, at salmonellosis, staphylococcal salmonellosis, staphylococcal infection); infection);
c) c) virusesviruses (for example, adenoviruses); (for example, adenoviruses); d) d) helminthshelminths..
Etiology of digestion insufficiency (cont):
5. Organic effects: a) congenital anomalies of digestive system; b) postoperative conditions; c) tumours of digestive system.6. Disorders of nervous and humoral regulation. Disorders of
digestion can develop during: a) psychoemotional disorders (neurotic and neurosis-like
conditions); b) mental diseases (schizophrenia, a manic - depressive syndrome); c) organic diseases of the central nervous system (encephalites); d) lesions of peripheral structures of vegetative nervous system; e) reflex disorders (various viscero-visceral reflexes).
Disorders of humoral regulation of digestion may be connected to disorders of synthesis and secretion of gastrointestinal hormones (gastrine, secretin, cholecystokinin-pancreazymin etc.).
Syndromes of digestion Syndromes of digestion InsufficiencyInsufficiency
• 1) starvation; • 2) dispeptic syndrome; • 3) dehydratation; • 4) disturbance of the acid-basic balance; • 5) intestinal autointoxication; • 6) the painful syndrome.
Dispeptic syndromeDispeptic syndrome includes different includes different combinations of the combinations of the following symptoms: following symptoms:
a) anorexia, a) anorexia, b) heartburn, b) heartburn, c) eructation, c) eructation, d) nausea, d) nausea, e) vomitting, e) vomitting, f) meteorism, f) meteorism, g) constipations,g) constipations, h) diarrhea.h) diarrhea.
AnorexiaAnorexia is a full absence of appetite is a full absence of appetite combined with an objective need of combined with an objective need of
foodfoodThere are following kinds of anorexia:There are following kinds of anorexia: аа) ) intoxicalintoxical – develops during acute and chronic poisonings (for example, salts – develops during acute and chronic poisonings (for example, salts
of mercury, medical products, bacterial toxins); of mercury, medical products, bacterial toxins); b) b) dispepticdispeptic –arises at diseases of digestive system, has more often behavior- –arises at diseases of digestive system, has more often behavior-
reflex nature; reflex nature; c) c) neurodynamicneurodynamic – develops as a result of reciprocal inhibition of the appetite – develops as a result of reciprocal inhibition of the appetite
centre after overexcitation of separate structures of limbic systems (for centre after overexcitation of separate structures of limbic systems (for example, a painful syndrome during heart attacks, colics, peritonitis); example, a painful syndrome during heart attacks, colics, peritonitis);
d) d) neuroticneurotic – it is connected with excessive excitation of cortex brain and – it is connected with excessive excitation of cortex brain and strong emotions (especialy negative); strong emotions (especialy negative);
e) e) psychogenicpsychogenic – is connected with conscious restriction of food (for example, – is connected with conscious restriction of food (for example, with an aim of getting thin or as result of mental disorders); with an aim of getting thin or as result of mental disorders);
f) f) neuroendocrinopathyneuroendocrinopathy – is caused by organic lesions of the central nervous – is caused by organic lesions of the central nervous system (hypothalamus) and endocrine diseases (hypophysial cachexia, system (hypothalamus) and endocrine diseases (hypophysial cachexia, Addison’s disease).Addison’s disease).
In the basis of development of anorexia two mechanisms may take In the basis of development of anorexia two mechanisms may take place: place:
1) 1) reduction of excitability of the food centrereduction of excitability of the food centre (intoxical, dispeptic, (intoxical, dispeptic, neuroendocrinopathy anorexia); neuroendocrinopathy anorexia);
2) 2) inhibition of food centre neuronsinhibition of food centre neurons (neurodynamic, neurotic, psychogenic (neurodynamic, neurotic, psychogenic anorexia). anorexia).
► The heartburnThe heartburn is a feeling of heat or burnings is a feeling of heat or burnings along the esophagus. Its development is connected along the esophagus. Its development is connected with irritation of receptors of the esophagus during with irritation of receptors of the esophagus during pelting contents of stomach into an esophagus pelting contents of stomach into an esophagus gullet (reflux). gullet (reflux).
It may be caused by: It may be caused by: аа) a large quantity of formed gastric juice; ) a large quantity of formed gastric juice; b) functional insufficiency of cardial sphincter.b) functional insufficiency of cardial sphincter.► MeteorismMeteorism is surplus accumulation of gases in the is surplus accumulation of gases in the
digestive channel due to their increased formation digestive channel due to their increased formation or insufficient removing from intestines. or insufficient removing from intestines.
► DiarrheaDiarrhea is a frequent emptying of intestines with is a frequent emptying of intestines with discharging of diluted and plentiful excrements.discharging of diluted and plentiful excrements.
The eructationThe eructation is a sudden involuntary allocation into oral cavity of is a sudden involuntary allocation into oral cavity of gas from a stomach esophagus, sometimes with small portions of gas from a stomach esophagus, sometimes with small portions of stomach contents.stomach contents.
The nauseaThe nausea is a burdensome sensation in epigastric area, chest and is a burdensome sensation in epigastric area, chest and in oral cavity, quite often previous to vomitting and frequently is in oral cavity, quite often previous to vomitting and frequently is accompanied general weakness, sweatness, increasing of salivation, accompanied general weakness, sweatness, increasing of salivation, coldness of arms and legs, pallor of skin, decrease of arterial coldness of arms and legs, pallor of skin, decrease of arterial pressure that is connected to activation parasympathetic nervous pressure that is connected to activation parasympathetic nervous system. In the basis of nausea stays excitation of the emetic centre, system. In the basis of nausea stays excitation of the emetic centre, which is insufficient for occurrence of vomitting.which is insufficient for occurrence of vomitting.
VomittingVomitting is the is the complex-reflex act complex-reflex act which results to which results to eruption of stomach eruption of stomach contents outside contents outside through the mouth. through the mouth. It is a result of the It is a result of the emetic centre emetic centre excitation which is excitation which is situated in medulla situated in medulla oblongata.oblongata.
Constipations are slowing down, difficulted or regularly insufficient emptying of intestines.• There are two mechanisms of development of constipations - spastic
and atonic. The first is caused by long constant contraction of smooth muscles of intestines, the second – because of their atonia.
Spastic constipations are: • а) inflammatory - arise owing to local spastic reflexes with changed
mucous membrane; • b) proctogenic - develop in case of anorectal area pathology; • c) mechanical – arise in case of impassability of guts; • d) toxic – is a result of poisonings by lead, mercury, thallium.Atonic constipations are: • а) alimentary – develop with consuming of light food containing (little
quantity of) cellulose; • b) neurogenic – is result of disorders of nervous regulation of intestinal
motility; • c) hypodynamic – arise in bed-patients, old men, people with very low
motor activity; • d) constipations in case of anomalies of thick gut (Girshprungs
disease); • e) constipations as a consequensce of water-electrolyte metabolism
disorders.
The pain frequently accompanies development of the alimentary channel diseases.
There are following mechanisms of pain occurrence at lesions of digestive organs:
• а) the spastic mechanism. The pain is caused by a spasm of smooth muscles of different parts of the alimentary tract. It is considered, that in this case the reason of pain is constriction of the vessels which are laying in the wall of hollow organs owing to what the ischemia develops. It causes appearance of metabolic products from the working organs, and their influence on pain receptors. At sharply arising strong spasm colic pain develops;
• b) the hypotonic mechanism. At reduction of smooth muscles tone (hypotonia) the pain appears from stretching of the wall of hollow organs (stomach, guts, gall bladder) by their contents. Thus the mechanical stretching of tissues causes irritation of the nervous endings;
• c) influence of biological active substances (histamine, serotonin, kinines, prostaglandins) on the nervous endings.
Disturbance of stomach functionsDisturbance of hydrochloric acidHydrochloric acid is excreted by parietal cells of mucous membrane of stomach which number in a healthy person is about 1 billion. Secretion of it is regulated by complicated mechanisms which include three interconnected phases of secretion: neurogenic (vagal), gastric (gastrine) and intestinal which is regulated by irritation of receptors and intestinal hormones.In regulation of functional activity of parietal cells nervous system (through mediator acethylcholine), and also various hormones (serotonin, insulin) take place. 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). Stimulation of H2-histamine receptors promotes formation of cAMP and stimulation of CCK-receptors and M3-receptors results to increasing of endocellular calcium (Са++) level. Besides the stimulation of M3-receptors increases, in comming of Са++ into a cell and due to increasing of inositolthreephosphate (IP3) level strengthens an output of endocellular Са++. Gastrin, cholecystokinin and histamine also raise output of Са++ due to action on IP3. Parietal cell has a receptor for prostaglandin E2 (PGE2) stimulation which reduces level of cAMP and results to inhibition of hydrochloric acid secretion.
In the basis of indigestion the following disturbances of functions of digestive system
may take place:1. Disturbance of secretion in digestive system: A. Hypersecretion conditions: 1) hypersalivation, 2) gastric hypersecretion, 3) pancreatic hypersecretion, 4) hypercholia;
2. Disturbance of motor function of the alimentary channel:1) disturbance of chewing, 2) disturbances of swallowing - dysphagia, 3) gastric dyskinesias, 4) intestinal dyskinesias, 5) dyskinesia of gall bladder and biliary ducts, 6) disturbances of defecation.
3. Disturbance of absorbtive functions - syndrome of malabsorption.
Disturbance of stomach motor function Disturbance of stomach motor function is called gastric diskinesia.
There are two kinds of gastric diskinesia: hypertonic and hypotonic.• Hypertonic kind is characterised by strengthening of peristaltics
(hyperkinesia) and increasing of stomach muscles tone (hypertonia).
• The hypotonic kind, on the contrary, is characterized by hypotonia and hypokinesia.
The reasons of motor gastric disturbance of hypertonic type may be: а) some food factors (rough food, alcohol); b) increase of gastric secretion; c) increase of a tone of vagal nerve; d) some gastrointestinal hormones (motilin).Hypertension and hyperkinesia of stomach leads: 1) to a long delay of food in stomach that promotes increase of
gastric secretion and development of ulcers on mucous membrane;
2) to development of antiperistaltics of stomach that results in development of dispeptic disturbances (eructation, nausea, vomitting).
Reduction of motor activity of Reduction of motor activity of stomach may be caused by:stomach may be caused by:Reduction of motor activity of Reduction of motor activity of stomach may be caused by:stomach may be caused by:
аа) alimentary factors (fat food); ) alimentary factors (fat food); b) reduction of gastric secretion b) reduction of gastric secretion
(hypoacid gastritis); (hypoacid gastritis); c) reduction of vagal nerve tone; c) reduction of vagal nerve tone; d) action inhibiting motility of stomach d) action inhibiting motility of stomach
through gastrointerstitial hormones through gastrointerstitial hormones (gastroinhibiting peptide, secretine (gastroinhibiting peptide, secretine etc.); etc.);
e) removal of pyloric part of stomach; e) removal of pyloric part of stomach; f) the common weakening of organism, f) the common weakening of organism,
an exhaustion, gastroptosis.an exhaustion, gastroptosis.• At At hypotonic diskinesiashypotonic diskinesias time of time of
food staying in the stomach is food staying in the stomach is shortened that conducts to shortened that conducts to disturbance of its digestion. Action of disturbance of its digestion. Action of the undigested components of food the undigested components of food on receptors of guts mucous on receptors of guts mucous membrane causes the increase of membrane causes the increase of peristaltics and diarrhea.peristaltics and diarrhea.
Gastritis Chronic gastritis and prolonged
inflammation of the stomach may be caused by either benign or malignant ulcers of the stomach or by the bacteria Helicobacter pylori.
Chronic gastritis is sometimes associated with autoimmune diseases such as pernicious anemia; dietary factors such as caffeine; the use of medications, especially NSAIDs; alcohol; smoking; or reflux of intestinal contents into the stomach.
Pathophysiology of gastritis
In gastritis, the gastric mucous membrane becomes edematous and hyperemic (congested with fluid and blood) and undergoes superficial erosion. It secretes a
scanty amount of gastric juice, containing very little acid but much mucus. Superficial ulceration may occur and can lead to hemorrhage.
The reasons and pathophysiologic
mechanisms of stomach ulcer 1. Psychoemotional negative overstrains
2. Stress.
3. Hereditary predisposition.
4. Errors in nutrition meal
5. Chronic gastritis and duodenitis with increased secretion of glands of mucus membrane.
6. Microbic factor – Helicobacter pylori.
7. Harmful habits – smoking, overindulge of alcohol
Pathogenesis of Ulcers
Aggressive Factors Acid, pepsin Bile salts Drugs (NSAIDs) H. pylori
Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori.
Helicobacter pyloriHelicobacter pylori These bacterias produce a These bacterias produce a lot enzymeslot enzymes ( (urease, protease, urease, protease,
phospholipasephospholipase), damaging protective barrier of mucous ), damaging protective barrier of mucous membrane, and also various cytotoxins. membrane, and also various cytotoxins.
The most pathogenic are The most pathogenic are Vac A-strainVac A-strain, that produce , that produce vacuolizating cytotoxinvacuolizating cytotoxin which results in formation of which results in formation of cytoplasmatic vacuoles and destructions of epithelial cytoplasmatic vacuoles and destructions of epithelial cellscells, and the , and the Cag A-strainCag A-strain which which expresses gene expresses gene associated with cytotoxinassociated with cytotoxin. This gene codes protein which . This gene codes protein which has has direct damaging effect on mucous membranedirect damaging effect on mucous membrane. .
H. pyloriH. pylori promotes liberation in mucous membrane of stomach promotes liberation in mucous membrane of stomach interleukines, lysosomal enzymes, TNFinterleukines, lysosomal enzymes, TNFαα, that causes , that causes development of inflammatory processesdevelopment of inflammatory processes in the mucous in the mucous membrane of stomach. membrane of stomach. Pathophysiologic mechanismsPathophysiologic mechanisms of of duodenum ulcer development in 95 % of cases is associated duodenum ulcer development in 95 % of cases is associated with with HelicobacterHelicobacter. .
leads to increase of gastrin levelleads to increase of gastrin level hydrochloric acid secretionhydrochloric acid secretion. . deficiency of pancreatic bicarbonatesdeficiency of pancreatic bicarbonates promotes development promotes development
of duodenitis and besides causes of duodenitis and besides causes appearance of gastric appearance of gastric sites metaplasia in duodenumsites metaplasia in duodenum which are quickly contaminated which are quickly contaminated by Helicobacter. by Helicobacter.
Further in case of unfavourable course especially when there Further in case of unfavourable course especially when there are additional ethiology factors (hereditary predisposition, are additional ethiology factors (hereditary predisposition, 0 (1) 0 (1) group of bloodgroup of blood, smoking, psychological overstrain etc.). , smoking, psychological overstrain etc.).
Gastric and Duodenal Ulcers
A peptic ulcer is an excavation (hollowed-out area) that forms in the mucosal wall of the stomach, in the pylorus (opening between stomach and duodenum), in the duodenum (first part of small intestine), or in the esophagus.
A peptic ulcer is frequently referred to as a gastric, duodenal, or esophageal ulcer, depending on its location, or as peptic ulcer disease.
Clinical Manifestations of UlcerClinical Manifestations of Ulcer
Gastric:Gastric: Burning or gassy sensation Burning or gassy sensation
in high epigastric area in high epigastric area Occurs within ½ hr. after Occurs within ½ hr. after
eating, food can worsen eating, food can worsen symptomssymptoms
Rarely occurs at nightRarely occurs at night Vomiting may ease Vomiting may ease
discomfortdiscomfort May lose weightMay lose weight Pyrosis Pyrosis
Duodenal:Duodenal: More cramplike discomfortMore cramplike discomfort Occurs on empty stomach, Occurs on empty stomach,
food relieves symptomsfood relieves symptoms Often occurs at nightOften occurs at night Vomiting uncommonVomiting uncommon May gain weightMay gain weight PyrosisPyrosis
Gastric ulcer
Duodenal ulcer
Disturbance of intestinal functions• Functions of intestines may be broken owing to
many organic diseases. In some cases these disturbances arise owing to disorders of nervous regulation of small and large intestine motility.
Disturbance of digestion and absorbtion in intestines
• The complex of disturbances which appear in an organism as a result of disturbance of digestion processes and absorbtion, has received the name of syndrome of maldigestion and malabsorbtion.
Syndrome of MalabsorbtionSyndrome of Malabsorbtion The syndrome of The syndrome of
malabsorbtion is a complex of malabsorbtion is a complex of symptoms whichsymptoms which appears appears result ofresult of absorbtion disturbanceabsorbtion disturbance of of substances in guts. substances in guts. Disturbance of absorbtion in guts Disturbance of absorbtion in guts may be caused by disturbances may be caused by disturbances that appear on three levels:that appear on three levels:
• The syndrome of maldigestion is disturbances of primary digestion, caused by insufficient reception of digestive enzymes into guts in particular in case of pancreatic hyposecretion.
• This syndrome is presented by:
1) disturbance of digestion of fats (absence of lipase and phospholipase). About 60-80 % of fat that gets into intestines is deduced with feaces – steatorrhea (fat in feaces);
2) disturbance of absorbtion of fat-soluble vitamins – causes the development of hypovitaminosis A, E and K;
3) disturbance of proteins digestion (absence of digestive proteases). About 30-40 % of food proteins are not acquired. In feaces there is a plenty of muscular fibres;
4) disturbance of digestion of carbohydrates (absence of amylases);
5) disturbance of decomposition of nucleinic acids (absence of nucleases).
Disturbances of intestine motor function Disturbances of intestine motor function • Disturbances of motor function of guts refer to intestinal diskinesia.
There are two types of intestinal diskinesia: • hyperkinetic (strengthening of the peristaltics, segmentary and
pendulum-like movements, and is manifastatied as diarrheas).• hypokinetic (weakening of motor activity of guts which result to
development of constipations). The reasons of intestinal diskinesias of hyperkinetic type may be: а) increase excitability; b) action unusual, pathological irritators undigested food (for example, for
achylia), products of rotting and fermentation, toxic substances etc. on receptors of guts.;
c) increase of the centres of vagal nerve excitability; d) increase of some gastrointerstitial hormones formation that strengthen
peristaltics of guts (motilin).
• Intestinal dyskinesias of hypokinetic type are manifestated by reduction intestinal peristaltics. That results in appearance of constipations. According to mechanisms of development there are two kinds of constipations: spastic and atonic.
IleusIleus is a disruption of the normal is a disruption of the normal propulsive gastrointestinal motor activity propulsive gastrointestinal motor activity from non-mechanical mechanismsfrom non-mechanical mechanisms
Motility disorders that result from structural Motility disorders that result from structural abnormalities are termed mechanical abnormalities are termed mechanical bowel obstruction.bowel obstruction.
Obstruction of venules and lymphatics in bowel wall
Edema of bowel wall
Ischaemia of bowel wall
Necrosis of bowel wall
Enterotoxemia
Death
Rupture of bowel wall
Peritonitis
PATHOPHYSIOLOGY OF LIVER• The main liver functions are as follows: metabolic, disintoxicative, bile
forming and bile excretory. Besides that, liver participates in digestion, blood coagulation, thermoregulation, hemodynamics, phagocytosis and other processes.
• Ethiology of liver functions violation• Liver diseases are caused by the great number of factors:1) Infectious agents – hepatitis virus, Koch’s bacillus, Actynomyces,
Echinococcuses, Ascarises etc.;2) Hepatotropic poisons, including medicines – tetracycline,
Liver diseases pathogenesis is Liver diseases pathogenesis is characterized by two main mechanismscharacterized by two main mechanisms::
- the - the direct hepatocytes affectiondirect hepatocytes affection – dystrophy, – dystrophy, necrosis;necrosis;
- - autoimmune injuryautoimmune injury of hepatocytes by of hepatocytes by autoantibodies, which are formed in response to autoantibodies, which are formed in response to hepatocytes antigens structure changed.hepatocytes antigens structure changed.
Liver affection by any of the above described Liver affection by any of the above described etiologic factors may lead to such state, when the etiologic factors may lead to such state, when the liver becomes not capable to execute its functions liver becomes not capable to execute its functions and to provide the homeostasis. That state is called and to provide the homeostasis. That state is called the the liver insufficiencyliver insufficiency. It may be total, when all . It may be total, when all functions are suppressed; or partial, when only functions are suppressed; or partial, when only some functions suffer, e.g., the bile-forming one. some functions suffer, e.g., the bile-forming one.
Animation of mechanical waves in liver during MRE.
Metabolic functionMetabolic function failurefailure
► Liver is the central organ of the chemical Liver is the central organ of the chemical homeostasis. It is placed between the homeostasis. It is placed between the collar collar veinvein from one side, and the from one side, and the systemic systemic circulationcirculation from the other. Its placement from the other. Its placement should be recognized as the optimal one for should be recognized as the optimal one for the execution of the metabolic function. the execution of the metabolic function.
► The The metabolic liver functionmetabolic liver function means liver means liver participation in the chemical elements participation in the chemical elements metabolism of almost all classes – carbons, metabolism of almost all classes – carbons, fats, proteins, enzymes, vitamins. fats, proteins, enzymes, vitamins. HepatocytesHepatocytes affection negatively influences affection negatively influences each of those metabolisms.each of those metabolisms.
Carbohydrate Carbohydrate metabolism metabolism
disorderdisorder
The The slowing-down of glycogen splittingslowing-down of glycogen splitting in liver is conditioned in liver is conditioned by corresponding enzymes by corresponding enzymes defect or their total absencedefect or their total absence. The . The diseases belonging to that group are called diseases belonging to that group are called glycogenosisesglycogenosises, , all being of inheritable origin. They are manifested by all being of inheritable origin. They are manifested by glycogen accumulation in liver, by hepatomegalia and glycogen accumulation in liver, by hepatomegalia and hypoglycemia. Several forms are distinguished among them, hypoglycemia. Several forms are distinguished among them, depending which enzymes is not synthesized.depending which enzymes is not synthesized.
GlycogenGlycogen synthesis synthesis and its splitting are the and its splitting are the main regulatory processes, with the help of main regulatory processes, with the help of which liver which liver keeps glucose homeostasiskeeps glucose homeostasis, , particularly its level in blood. The slowing-particularly its level in blood. The slowing-down of glycogen synthesis may happen at down of glycogen synthesis may happen at any hepatocytes affection. any hepatocytes affection. That leads to the simultaneous That leads to the simultaneous limitation of glucuronic acid limitation of glucuronic acid formationformation, which is indispensable in , which is indispensable in disintoxication of many disintoxication of many exogenic poisonsexogenic poisons (industrial toxins) and final metabolites (industrial toxins) and final metabolites (cadaverine, putrescine) and (cadaverine, putrescine) and unconjugated bilirubinunconjugated bilirubin..
Fat metabolism disorder. Liver fatty infiltrationFat metabolism disorder. Liver fatty infiltration• Exogenic triglycerides are hydrolyzed in the intestines, and in
enterocytes they are resynthesized and come into the liver as a part of hylomicrones. They come into hepatocytes and are decomposed to fatty acids and glycerin. Fatty acids are partly oxidized and partly participate in the formation of triglycerides, phospholipids and cholesterin ethers. The formed triglycerides are expelled by the liver into blood in the form of lipoproteides of very low and of low density.
• The production of lipoproteides by the liver demands the close linkage of the processes of lipidic and albumin synthesizes. The availability of the starting products is also indispensable, but in the balance amount. The reason of fats infiltration can be any agent, which violates this balance in such way, that lipids amount become higher in the correlation to albumins amount. In the result of that it is impossible to involve the liver lipids into the synthesis of lipoproteides and to excrete them into blood. A part of lipids deposits in liver.
FATTY FATTY LIVERLIVER
ObesityDiabetes
Toxic
Protein metabolism infringementProtein metabolism infringement• The main consequences of albumin metabolism infringement
at the liver affection are as follows:a) Hypoproteinemia is the result of blood level decrease of
albumins, α- and β-globulins, which are synthesized by hepatocytes. It leads to hypooncia and as the result edema develops.
b) Hyper-gamma-globulinemiais the result of gamma-globulines synthesize increase by Kuffer’s cells and plasmocytes.
c) Dysproteinemia is the result of macroglobulins and crioglobulins accumulation.
d) Hemorrhagic syndrome in the result of the decreased synthesis of blood coagulation factors (besides VIII factor).
e) The increase of blood RN (retarded nitrogen) in the result of the decreased urea synthesis and ammonia accumulation. That happens at 80% parenchyma affection.
f) Increase of enzymes level in blood (aminotranspherases).
Microelements metabolism disorder
• At the long-term copper accumulation by abnormal metall-thionein, the binding centres satiate, and copper excess is absorbed by liver lysosomes.
• The metal is accumulated in hepatocytes and leads to hepatomegalia.
• The well-known example is Wilson’s disease, when copper deposits in hepatocytes. Normally, the copper, which comes into a Normally, the copper, which comes into a hepatocyte, is distributed among the cytoplasm and the subcellular organels. hepatocyte, is distributed among the cytoplasm and the subcellular organels. • There is a special albuminspecial albumin in the liver – metall-thioneinmetall-thionein, which binds copper. It functions as a temporal copper depositor. In some time, the deposited copper enters the metal-containing enzymes, or is withdrawn with bile.
Mechanism of fibrosis and
cirrhosis of the
liver
The characteristic diffuse The characteristic diffuse nodularity of the surface reflects nodularity of the surface reflects the interplay between nodular the interplay between nodular regeneration and scarring. The regeneration and scarring. The greenish tint of some nodules is greenish tint of some nodules is due to bile stasis.due to bile stasis.
Blind Man’s Blind Man’s
DiagnosisDiagnosis
Antitoxic function disorder• The antitoxic liver function aggravation is connected to the
violation of certain reactions directed to rendering harmless the toxic substances, which are formed in an organism or come from outside:
a) Urea synthesis disorder resulting in ammonia accumulations.
b) Conjugation disorder, i.e. the formation of pair compounds with glucuronic acid, glycin, cystine, taurine. In such way unconjugated bilirubin, scatol, indol, phenol, kadaverin, thyramin, etc. become harmless.
c) Acetylization disorder leading to sulphamides accumulation at their long-term usage. d) Oxidization disorder leading to the accumulation of aromatic carbons.Deep disorders of the antitoxic liver function bring forward liver encephalopathy and liver coma.
Hepatocerebral coma
• The main mechanism of the central nervous system damage is the accumulation of toxic neurotropic substances:
• a) Ammonia. In liver mytochondria urea is synthesized from ammonia. At liver affection, ammonia does not join the urea cycle (ornitative cycle). Ammonia binds with α-ketoglutaric acid and forms glutaminic acid. Exclusion of α-ketoglutaric acid from Krebs cycle slows down ATP and decreases energy outcome in neurons, decreases their repolarization and function.
• b) Rotting products, which are absorbed from the large intestine – phenol, indol, skatol, kadaverine, thyramine.
• c) Low-molecular fatty acids – oleic, capronic, valeric. They interact with lipids of neurons membranes and slow down the excitement transfer.
The Hepatocerebral coma is a syndrome developing in the result of the liver insufficiency. It is characterized by the deep affection of the central nervous system (consciousness loss, reflexes loss, cramps, blood flow and breathing disorders).The most frequent liver coma reasons are as follows: viral hepatitis, toxic liver viral hepatitis, toxic liver dystrophy, cirrhosis, portal hypertensiondystrophy, cirrhosis, portal hypertension.
Disorders of bile formation and secretion The main indicator of bile formation and bile secretion is the secretion of bile pigments, i.e. bilirubin and its derivatives. Unmconjugated bilirubin is not soluble in water. In blood, 75 % of it binds with albumin and circulates in such form. Unconjugated bilirubin approaches the hepatocyte and binds with lipandin, the albumin placed on its surface, or with γ-albumin, which might be identical to glutation-5-transpherase. Ligandin transports unconjugated bilirubin to microsomes, where it binds with glucuronic acid (conjugation). Monoglucuronide and bilirubin dyglucuronide are formed. The conjugated bilirubin is secreted into the duodenum and is removed from the organism as stercobilin with feces and urine. A part of the conjugated bilirubin is restored up to urobilinogen in liver ducts, gallbladder and small intestines under the influence of microflore enzymes. Urobilinogen does not enter the general blood flow and normally is not excreted. It is absorbed into the liver vein and is splitted by the liver to pirolites.The violation of bile formation and bile excretion is manifested by characteristic syndromes: jaundice, cholemia and steatorrhea.
Jaundice (icterus)Jaundice (icterus) This means yellowishing of skin, mucous membranes and sclera in This means yellowishing of skin, mucous membranes and sclera in
the result of bile pigments depositing in them. There are three types the result of bile pigments depositing in them. There are three types of jaundice:of jaundice:
A. A. HemolyticHemolytic jaundice, conditioned by the surplus formation of jaundice, conditioned by the surplus formation of unconjugated bilirubin or by the violation of its transportation.unconjugated bilirubin or by the violation of its transportation.
B. B. ParenchimatousParenchimatous jaundice, conditioned by hepatocytes pathology. jaundice, conditioned by hepatocytes pathology.C. C. ObstructiveObstructive jaundice, which takes place on the basis of the jaundice, which takes place on the basis of the
insufficient bile outflow.insufficient bile outflow. The The normal plasma concentration of bilirubin normal plasma concentration of bilirubin is maximally 17 μmol/L (1 is maximally 17 μmol/L (1
mg/dL). If it rises to more than 30 μmol/L, the sclera become yellow; if the mg/dL). If it rises to more than 30 μmol/L, the sclera become yellow; if the concentration rises further, the skin turns yellow as well (concentration rises further, the skin turns yellow as well (jaundice jaundice [icterus]). Several forms can be distinguished:[icterus]). Several forms can be distinguished:
This means yellowishing of skin, mucous membranes and sclera in This means yellowishing of skin, mucous membranes and sclera in the result of bile pigments depositing in them. There are three types the result of bile pigments depositing in them. There are three types of jaundice:of jaundice:
A. A. HemolyticHemolytic jaundice, conditioned by the surplus formation of jaundice, conditioned by the surplus formation of unconjugated bilirubin or by the violation of its transportation.unconjugated bilirubin or by the violation of its transportation.
B. B. ParenchimatousParenchimatous jaundice, conditioned by hepatocytes pathology. jaundice, conditioned by hepatocytes pathology.C. C. ObstructiveObstructive jaundice, which takes place on the basis of the jaundice, which takes place on the basis of the
insufficient bile outflow.insufficient bile outflow. The The normal plasma concentration of bilirubin normal plasma concentration of bilirubin is maximally 17 μmol/L (1 is maximally 17 μmol/L (1
mg/dL). If it rises to more than 30 μmol/L, the sclera become yellow; if the mg/dL). If it rises to more than 30 μmol/L, the sclera become yellow; if the concentration rises further, the skin turns yellow as well (concentration rises further, the skin turns yellow as well (jaundice jaundice [icterus]). Several forms can be distinguished:[icterus]). Several forms can be distinguished:
Hemolytic jaundice• Appears, as a rule, in the result
of the excess erythrocytes haemolysis. Its reasons are the same as for the haemolytic anaemia. The special features of bile pigments exchange at this jaundice are as follows:
1) in the blood – high level of unconjugated bilirubin;
2) in the feaces – stercobilin concentration is increased;
3) in the urine – stercobilin concentration is increased too,
4) no cholemia.
Parenchymatous jaundice is conditioned by endogenic (inheritable) and outside influences.
• The basis of inheritable hepatic jaundice is the violations of the unconjugated bilirubin capture by hepatocytes, its insufficient conjugation or its insufficient isolation of the conjugated bilirubin from the hepatocyte.
Parenchymatous jaundiceParenchymatous jaundice is characterized by the following violations of bile pigments metabolism: A) in the blood – the unconjugated bilirubin concentration is increased and the conjugated bilirubin appears; B) in the feces – stercobilin drops; C) in the urine – stercobilin drops, the appearance of urobilin and conjugated bilirubin.
Cholelithiasis (pigmental stones)• Obstructive jaundice is connected with the
obstruction for bile outflow (tumour, cholelithiasis).• Peculiarities of bile pigments metabolism at this type
of jaundice are as follows: • in the blood – the conjugated bilirubin usually are elevated; Blood levels of bile acids often are elevated
in obstructive jaundice.• feces – clay colored because of the lack of bilirubin in the bile; • urine - is dark.
• Cholemic syndrome appears at obstructive and parenchimatous jaundices, when bile comes into blood. It is caused by bile acids and the main symptoms are:
• Steatorea is a syndrome, which is based on the violation of digestion and fats absorption. Fats are excreted with feces. The fat-like vitamins are being lost together with fats.
Portal hypertensionPortal hypertension
DDevelopment of portal hypertensionevelopment of portal hypertension Characterized by, that displays by Characterized by, that displays by triad signtriad sign: :
2)2) capute medusaecapute medusae – varicose veins – varicose veins of front wall of abdomen, veins of of front wall of abdomen, veins of gullet (esophagus), and rectal veins, gullet (esophagus), and rectal veins,
3)3) splenomegalysplenomegaly. .
Portal hypertension
Increased pressure inperitoneal capillaries
Portosystemicshunting of
blood
Splenomegaly
AscitesDevelopment of
collateral channels
Caputmedusae
Esophagealvarices
Hemorrhoids
Shunting of ammonia
and toxins from theintestine into the
general circulation
Hepaticencephalopath
y
Anemia
Leukopenia
Bleeding
Thrombocytopenia
Mechanisms of disturbed liver function Mechanisms of disturbed liver function related to portal hypertensionrelated to portal hypertension.
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