peptic ulcer disease - russian state medical...

Peptic ulcer disease

Bogush N.L.

Definition

Peptic ulcer disease (PUD) -

it is a chronic intermittent and recurrent

disease with a defect in the mucosa of

stomach or duodenum that extends through

the muscularis mucosa into the submucosa

or deeper.

Symptomatic ulcers

A breach in the mucosa arise:

• By stress

• By intake of some medical drugs

• As complications at:

Cushing disease, Wakesa disease, leukemias,

diabetes mellitus, chronic diseases of the liver,

kidneys, brain, atherosclerosis.

• By Zollinger-Ellison syndrome

Etiology of PUD

Theories:

• 1. Mechanical (Ashoff)

• 2. Inflammatory

• 3. Vascular (Virchov)

• 4. Peptic, autodigestion (Quinke)

• 5. Cortex-visceral

• 6. Infectious

• 7. Inherited

Outward signs of hereditary

predisposition

• 1. Asthenic constitution

• 2. Blond hair

• 3. Blue eyes

• 4. Hand type – radial, foot type –

intermediate

• 5. Blood type – 0 (I), Rh “-”.

Hereditary predisposition

Such persons can have:

- level of maximal HCl secretion,

- content of pepsinogen I in the serum,

- gastrin secretion after meal

+

glycoproteins (GAG) in the mucus

Pathogenesis of PUD

• PUD arises as an imbalance between local

gastroduodenal protective mechanisms and

the aggressive damaging factors (exogenous

and endogenous).

I. Local protective mechanisms

• 1. The mucosa (with the mucus)

• 2. The mucus

• 3. The mechanism of antro-duodenal

inhibition or damping, that HCl secretion

• 4. Intensive blood circulation

Protective features of the mucus

• 1. A gel-like mucus film with thickness 0,1-0,5

mm thick.

• 2. Protects from mechanical injury.

• 3. Compounds:

acid GAG – fucose; neutral GAG –

N-acetylneuraminic acid (salic acid) = NANA.

• 4. Can’t be digested by pepsin.

• 5. Prevents direct contact of the juice, acid with

the epithelium.

Protective mechanisms of the mucosa -1

• 1. A mucus production.

• 2. Tight cells junctions (keep H+ in the lumen).

• 3. Bicarbonate production ( HCl within mucosa).

• 4. Prostaglandin E production.

• 5. Synthesis of IgA antibodies (due to plasma

cells).

• 6. High ability of regeneration important for

epithelial repair and wound healing.

Epithelial repair and wound healing.

• Healing of light epithelial arrosion – through

sideward epithelial cells migration along the basal

membrane. Takes 30 min.

• Healing of more deep defects – through

proliferation, which takes more time. Growth

factors are: EGF-like growth factor, TGF, IGF-1,

gastrin-releasing peptide.

• Healing of big defects – through the inflammation.

Protective mechanisms of the mucosa -2

• 7. Intensive blood circulation (sympathetic N.S.).

• 8. Many mast cells – regulate the blood flow.

• 9. Antro-duodenal inhibitory reflex – regulates

HCl production: pH in antrum to 2-2,5 or pH in

duodenum to 4,0 inhibition of HCl secretion.

• 10. Neuro-endocrine regulation of gastric juice

secretion: synthesis of gastrin, secretin,

somatostatin; innervation with n.vagus endings.

Protective role of prostaglandins E2 and I2.

• 1. Stimulate the mucus synthesis.

• 2. They synthesis of GAG (mucopolysaccharides) and hydrophobic properties of the mucus.

• 3. They synthesis of bicarbonates.

• 4. They intensity of the blood flow.

• 5. They HCl secretion.

So, they act as potent gastroprotectors.

II. Endogenous damaging

factors.

• 1. Acid-peptic factor.

• 2. Motordisfunction of stomach and

duodenum.

• 3. Disorders of neuro-humoral regulation

(n.vagus).

• 4. Disorders of cells and humoral immunity.

The STOMACH

Esophagus

Cardia

Fundus

Parietal cells (H+)

Body

Chief cells (pepsin)

Duodenum

Pyloric

canal

Pylorus Antrum

G-cells

(gastrin)

Carbonic anhydrase

CO2 HCO3¯ Cl¯

H20

Diffusion

Ach

M1-r

M2-r Ach

G-cell

Hist prod.

cell

Parietal

cell

Ganglion

Intramural

neuron

G-r

gastrin

H2-r

Histamin

Ca++

H+

Ach –acetylcholin;

r - receptor

Stimulators of HCl secretion

Proton

pump

Functions of the stomach .

• 1. Reservoir

• 2. Secretory

• 3. Motility

• 4. Evacuatory

• 5. Excretory

Morfofunctional types of gastric secretion.

• 1. Normal – N HCl and pepsin in gastric

juice.

• 2. Hyperchlorhydremic - HCl, N pepsin.

• 3. Hyperpepsinogenic – N HCl, pepsin.

• 4. Pyloric - HCl, pepsin.

• 5. Hypochlorhydremic - HCl, N pepsin.

• 6. Hypopepsinogenic – N HCl, pepsin.

• 7. Achylic - HCl, pepsin.

Gastric juice secretion.

During an intubation 3 portion of the juice:

I portion – the juice from the empty stomach.

II portion – juice secretion as a response on the tube mechanical irritation – the basal secretion. Depends from neuro-humoral regulation!

III portion - juice secretion as a response on chemical stimuli: injection of histamin or pentagastrin. Depends from amount of the parietal cells (hereditary).

Regulation of gastric juice

secretion.

• The stimulators are: n. vagus tonicity,

gastrin, histamin, glucocorticoids,

parathyroid hormone, bombesin,

enkephalins…

• The inhibitors are: mineralcorticoids,

sectretin, glucagon, somatostatin…

Proteolytic activity of gastric

juice

The coefficient of proteolytic activity =

PEPSIN â (active)

common PEPSIN - PEPSIN â

= 0,3

The high concentration of H+ activates

pepsinogen into pepsin.

Acid-peptic factor – harmful action of

gastric juice.

1.Pathogenesis of ulcer at HCl hypersecretion.

HCl damage of mucosal barrier back

diffusion of H+ damage of endothelium

in the vessels occlusion of vessels

ischemia necrosis + pepsin action

fixation of the damage the ulcer.

2. Motordisfunction of the stomach and the

duodenum

• motor activity of the stomach rapid evacuation of acid contents duodenal ulcer(?)

• motor activity of the stomach long contact of stomach mucosa with acid contents stomach ulcer(?)

• The duodenal-gastric reflux, backward flow bile acids with lysolecitin appear in the stomach removing of mucus, epithelium damage stomach ulcer(?), mucous cells metaplasia (precancerous condition).

III. External damaging factors.

• 1. Nutritional factors.

• 2. Harmful, pernicious habits.

• 3. Helicobacter pylori.

• 4. Medicine.

• 5. Stress.

1.Nutritional factors.

• 1. Irregular meal fasting hypersecretion.

• 2. Starvation fasting hypersecretion, stress, negative nitrogen balance and bad mucosa regeneration.

• 3. Irritating food – spicy food, fruit juices, coffee, beer, wine…. gastric juice hypersecretion.

• 4. Empty stomach or refined products in the meal bad gastric juice absorption and HCl neutralization.

2. Harmful, pernicious habits.

• 1. Smoking blood flow, HCl-

secretion, motility, bicarbonate

secretion, Prgl E synthesis and mucosal

regeneration.

• 2. Alcohol intake moderate drinking of

wine and beer HCl-secretion, gastrin

production; alcohol in large quantities or in

high concentration damages the mucosa.

3. Helicobacter pylori (HP).

S-shaped gram “-” rod, lives under mucus. It has: 1) enzyme UREASE that produce NH3 from the urea, which defends the rod from HCl (+ C02, HCO3); 2) enzyme CATALASE which defends the rod from phagocytes.

HPs produce from the urea the toxic monochlora-mine; secret toxic lipases, proteases, phospho-lipases, produce toxic oxygen radicals and destroy the mucus and cells; excrete CO2 meteorism;

stimulate chemotaxis and secretion of Il-1, IL-6, Il-8, TNF; HCl-secretion; thrombus formation.

4. Medicine.

Aspirin, NSAiDs Prgl synthesis, bicarbonate

secretion, mucus formation +damage the

mucosa locally by nonionic diffusion into the

mucosal cells.

Reserpin Histamin secretion and so HCl

secretion.

Catecholamines spasm of vessels and ischemia.

Glucocorticoides HCl secretion, mucus

formation, regeneration, food evacuation.

5. Stress.

STRESS

Hypothalamus vegetative N.S.

ACTH cortisol vagus+symphat N.S.

Acch + Norepin

HCl, pepsin ( gastrin, histamin)

blood flow, regeneration

mucus formation; motordisfunction

Principles of Phatogenetic Therapy –1.

• The diet. Refuse from harmful habits.

• activity of acid-peptic factor: blockers of

1) M2-cholinoreceptors = cholinolytics; 2) gastrin

receptors; 3) H2-histamin receptors; 4) blockers of

proton pump; 5) antacids (HCl).

• growth of HP: 1) AB; 2) metronidasol; 3) drugs

with bismuth.

• Immunocorrectors.

Principles of Phatogenetic Therapy –2.

• Cell protectors: 1) drugs that defensive

mucus layer = polysaccharides + sulfur; 2)

drugs that mucus secretion = Prgl E.

• Sedatives.

• Analgetics.

• Surgery.

The dumping syndrome -1.

A stump from the stomach reservoir and motility function.

A meal I. Too rapid emptying distension + mechanical irritation of the gut (the pieces of food > 2 mm) nausea, bloating, flushing, pain in the abdomen; hypertonicity of chyme - H2O secretion and diarrhea; activation of kallikrein-kinine system (dilation of mesenterical vessels + their permeability) CBV activation of sympathetic N.S. ( catecholamines) cardiovascular reactions: palpitation,weakness...

[ 30-60 min after food intake – early D.S.]

The dumping syndrome -2.

II. glucose in the blood (especially when

sugar is in the food) secretion of

insulin 90-180 min after food intake

hyperglycemia changes into hypoglycemia:

confusion, loss of consciousness – late D.S.