Basic functions of the liver. Physiology of the hepato-biliary system

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The liver is the largest human gland- its weight is about 1.5 kg. The metabolic functions of the liver are extremely important for maintaining the vitality of the body. Metabolism of proteins, fats, carbohydrates, hormones, vitamins, neutralization of many endogenous and exogenous substances. Excretory function - bile secretion, necessary for the absorption of fats and stimulation of intestinal motility. Approx. released per day 600 ml bile.

Liver is an organ that performs the role blood depot. Up to 20% of the total blood mass can be deposited in it. During embryogenesis, the liver performs a hematopoietic function.
The structure of the liver. In the liver, epithelial parenchyma and connective tissue stroma are distinguished.

The hepatic lobule is the structural and functional unit of the liver.

The structural and functional units of the liver are the hepatic lobules numbering about 500 thousand. The liver lobules are shaped like hexagonal pyramids with a diameter of up to 1.5 mm and a slightly greater height, in the center of which is the central vein. Due to the peculiarities of hemomicrocirculation, hepatocytes in different parts of the lobule find themselves in different oxygen supply conditions, which affects their structure.

That's why in the lobule there are central, peripheral and between them intermediate zones. A feature of the blood supply to the hepatic lobule is that the intralobular artery and vein extending from the perilobular artery and vein merge and then the mixed blood moves through the hemocapillaries in a radial direction towards the central vein. Intralobular hemocapillaries run between the hepatic beams (trabeculae). They have a diameter of up to 30 microns and belong to the sinusoidal type of capillaries.

Thus, through the intralobular capillaries, mixed blood (venous - from the portal vein system and arterial - from the hepatic artery) flows from the periphery to the center of the lobule. Therefore, hepatocytes in the peripheral zone of the lobule find themselves in more favorable oxygen supply conditions than those in the center of the lobule.
By interlobular connective tissue, normally poorly developed, pass blood and lymphatic vessels, as well as excretory bile ducts. As a rule, the interlobular artery, interlobular vein and interlobular excretory duct go together, forming the so-called liver triads. The collecting veins and lymphatic vessels pass at some distance from the triads.

Hepatocytes. Liver epithelium.

Epithelium liver consists of hepatocytes, components 60% of all liver cells. Associated with the activity of hepatocytes perform most of the functions, characteristic of the liver. At the same time, there is no strict specialization between liver cells and therefore the same hepatocytes produce both exocrine secretion (bile), and by type endocrine secretion numerous substances entering the bloodstream.

Hepatocytes are separated by narrow gaps (space of Disse)– filled with blood sinusoids, in the walls of which there are pores. From two adjacent hepatocytes, bile is collected in bile capillaries>tubules of Genirga>interlobular tubules>hepatic duct. Moves away from him cystic duct to gallbladder. Hepatic + cystic duct = common bile duct into the duodenum.

Composition and functions of bile.

excreted in bile products of exchange: bilirubin, drugs, toxins, cholesterol. Bile acids are needed for emulsification and absorption of fats. Bile is formed by two mechanisms: GI-dependent and independent.

Liver bile: isotonic to blood plasma (HCO3, Cl, Na). Bilirubin (yellow). Bile acids (can form micelles, detergents), cholesterol, phospholipids.
In the bile ducts, bile is modified.

Cystic bile: water is reabsorbed in the bladder>^ concentration of org. substances. Active transport of Na, followed by the movement of Cl, HCO3.
Bile acids circulate (saving). They are isolated in the form of micelles. Absorbed passively in the intestine and actively in the ileum.
» Bile is produced by hepatocytes

The components of bile are:
Bile salts (= steroids + amino acids) Detergents capable of reacting with water and lipids to form water-soluble fatty particles
Bile pigments (result of hemoglobin degradation)
Cholesterol

Bile is concentrated and deposited in the gallbladder and is released from it during contraction
- Bile release is stimulated by the vagus, secretin and cholecystokinin

BILE FORMATION AND BILE EXCECTION.

Three important notes:

• bile is formed constantly, and is released periodically (therefore accumulates in the gallbladder);
• bile does not contain digestive enzymes;
• bile is both a secretion and an excretion.

COMPOSITION OF BILE: bile pigments (bilirubin, biliverdin - toxic products of hemoglobin metabolism. Excreted from the internal environment of the body: 98% with bile from the gastrointestinal tract and 2% by the kidneys); bile acids (secreted by hepatocytes); cholesterol, phospholipids, etc. Hepatic bile is slightly alkaline (due to bicarbonates).
In the gallbladder, bile concentrates and becomes very dark and thick. Bubble volume 50-70 ml. The liver produces 5 liters of bile per day, and 500 ml is secreted into the duodenum. Stones in the bladder and ducts are formed (A) with an excess of cholesterol and (B) a decrease in pH due to stagnation of bile in the bladder (pH<4).

MEANING OF BILE:

1. emulsifies fats,
2. increases the activity of pancreatic lipase,
3. promotes the absorption of fatty acids and fat-soluble vitamins A, D, E, K,
4. neutralizes NS1,
5. has a bactericidal effect,
6. performs an excretory function,
7. stimulates motility and absorption in the small intestine.

BILE ACIDS CIRCULATION: Bile acids are used repeatedly: they are absorbed in the distal ileum (ileum), enter the liver through the bloodstream, are captured by hepatocytes and are again released into the intestine as part of bile.

REGULATION OF BILE FORMATION: neuro-humoral mechanism. The vagus nerve, as well as gastrin, secretin, and bile acids increase the secretion of bile.

REGULATION OF BILE EXCECTION: neuro-humoral mechanism. The vagus nerve, cholecystokinin, causes contraction of the gallbladder and relaxation of the sphincter. Sympathetic nerves cause the bladder to relax (accumulation of bile).

NON-DIGESTIVE FUNCTIONS OF THE LIVER:

1. protective (detoxification of various substances, synthesis of urea from ammonia),
2. participation in the metabolism of proteins, fats and carbohydrates,
3. inactivation of hormones,
4. blood depot, etc.

Subject: Pathological physiology of the liver.

1. Liver functions and etiology of liver failure.
2. Metabolic disorders in liver pathology.
3. Violation of the antitoxic and barrier function of the liver.
4. Violation of bile formation and bile excretion.
5. Cholelithiasis.

1. Liver functions and etiology of liver failure.

The liver takes part:

1) in the metabolism of proteins, carbohydrates, fats, cholesterol;

2) fibrinogen, prothrombin, heparin;

3) enzymes, vitamins, pigments;

4) in water and mineral metabolism;

5) in the exchange of bile acids and bile formation;

6) in the regulation of total blood volume;

7) in barrier and antitoxic functions.

In addition, the liver is one of the main depots of proteins, carbohydrates, vitamins and other substances.

The main factors causing the development of pathological processes in the liver are:

1) Causative agents of infections and invasions and their toxins (streptococci, staphylococci, viruses, fasciola, etc.)

2) Industrial poisons (chloroform, mercury, lead, phosphorus, benzene, etc.)

3) Medicinal substances (sulfonamides, barbiturates, tetracycline, biomycin)

4) Plant poisons.

The above factors penetrate the organ through the portal vein, hepatic artery, bile ducts and lymphatic vessels of the liver.

As a result of their influence, an inflammatory process develops in the liver - hepatitis or dystrophic processes - hepatosis (for example, fatty liver (fatty hepatosis)).

Chronic hepatitis often leads to cirrhosis.

Cirrhosis (from the Greek kirros, Latin cirrus - red) is the degeneration of liver cells (hepatocytes) and a strong proliferation of connective tissue with its subsequent compaction, leading to diffuse shrinkage of the organ.

One of the consequences of cirrhosis is dropsy of the abdominal cavity (ascites), which develops as a result of:

1) stagnation of blood in the portal vein;

2) violation of lymph outflow;

3) hypoproteinemia and, as a result, a decrease in oncotic pressure.

Insufficiency of liver function is manifested in violation of:

1) metabolism;

2) barrier and antitoxic functions;

3) synthesis and secretion of bile;

4) composition and properties of blood;

5) functions of depositing various substances.

1. Metabolic disorders in liver pathology.

A) Disorders of carbohydrate metabolism.

The liver ensures the constant concentration of glucose in the blood.

This is done by a two-way process:

1) Glycogenogenesis (formation of glycogen from blood glucose and its deposition in the liver).

2) Glycogenolysis (glycolysis) – the formation of glucose from the glycogen depot in the liver and its release into the blood.

The activity of these two processes is controlled by blood sugar levels.

These processes are also greatly influenced by hormonal levels.

Hormones that increase glycogen deposition in the liver: ACTH, glucocorticoids and insulin.

Hormones that stimulate the breakdown of glycogen: growth hormone, glucagon, adrenaline.

With liver pathology, glycolysis decreases, which leads to hypoglycemia.

A decrease in glycogenogenesis is observed with prolonged muscular work in combination with poor feeding, with cachexia and infections accompanied by fever.

B) Protein metabolism disorder.

In the liver, bile acids are synthesized from free amino acids, fatty acids and a significant part of the enzyme protein are formed.

The liver is the only site of synthesis of plasma albumin and the main proteins of the blood coagulation system (fibryogen, prothrombin).

For liver damage:

1) the synthesis of albumins and globulins decreases, which leads to hypoproteinemia;

2) the level of fibrinogen and prothrombin decreases, which leads to a decrease in blood clotting;

3) the activity of various enzymes decreases;

4) the content of ammonia in the blood, a metabolite of protein synthesis, increases, which leads to intoxication of the body, stimulation of the central nervous system and convulsions.

B) Violation of fat metabolism.

The liver synthesizes from fatty acids, glycerol, phosphoric acid, choline and other bases the most important components of cell membranes - phospholipids, as well as metabolites of fatty acids - ketone bodies.

The liver is also involved in the metabolism cholesterol – an important component of blood plasma, the main source of corticosteroid hormones and vitamin D.

When an organ is damaged, the following occurs:

1) impaired fat oxidation, which causes fatty infiltration of the liver;

2) increased formation of ketone bodies, which leads to ketosis;

3) disruption of cholesterol metabolism, which can lead to atherosclerosis.

D) Violation of vitamin metabolism.

The liver is involved in the metabolism of almost all vitamins, mainly as a depot.

When the liver is damaged, the absorption of vitamins from the intestines, both water- and fat-soluble, sharply decreases.

A necessary condition for the absorption of fat-soluble vitamins is the presence of bile in the intestines.

D) Violation of mineral metabolism.

The liver is the central organ for the exchange and storage of copper, zinc and iron.

Excess copper is excreted from the body mainly with bile, so a violation of bile secretion causes an increased copper content in the blood and liver, which leads to intoxication.

The liver synthesizes a number of zinc-containing enzymes.

With cirrhosis, the zinc content in the liver and blood drops sharply.

The liver also regulates the absorption of iron in the intestines.

In cirrhosis, as a result of increased iron absorption, hemosiderin is deposited in tissues in large quantities, causing hemochromatosis, or “bronze diabetes”.

D) Violation of water metabolism.

The liver is a water depot, and due to albumin it maintains the colloid-osmotic balance of the blood, which is regulated simultaneously by oncotic pressure and osmotic pressure.

With severe liver damage (usually cirrhosis), this balance is disrupted, leading to ascites.

Note:

Osmotic pressure (osmosis) is pressure that prevents the release of fluid from vessels and capillaries into tissues, provided by the K+Na+ pump (this is a special protein - see biophysics).

Oncotic pressure (oncos) is pressure that prevents the release of fluid from the blood and lymphatic channels into the tissue, caused by the presence of proteins in the blood plasma and lymph.

They seem to “hold” liquid due to hydrophilic endings.

Both types of pressure maintain colloid-osmotic balance and, in general, homeostasis (constancy of the internal environment of the body).

1. Violation of the antitoxic and barrier function of the liver.

All the blood flowing from the intestines.

It passes through the portal vein to the liver and is neutralized there.

The antitoxic function of the liver is to convert both metabolites (metabolic products) common to the cell and substances foreign to the body.

Detoxification occurs by converting various substances into inactive complexes and removing them from the body:

1) Phenol, cresol, indole, skatole, etc. + sulfuric and glucuronic acids;

2) Glucuronic acid + bilirubin and steroid hormones;

3) Mercury, arsenic, lead + nucleoproteins.

With liver pathology, toxic substances from the intestines spread freely throughout the body, causing its poisoning.

The removal of foreign substances and various infectious agents from the blood and the utilization of blood pigments are carried out by Kupffer cells.

Therefore, when the liver is damaged, infectious diseases are more severe.

1. Violation of bile formation and bile excretion.

Disruption of the processes of formation and secretion of bile is observed in diseases of the liver and gall bladder, infectious diseases, blood diseases, etc. At the same time, pigment metabolism is also disrupted.

Scheme 1. Normal exchange of bile pigments.

Blood (free (protein) bilirubin) Þ

Yellowish color of plasma

Liver (+ glucuronic acid of hepatocytes) Þ separation from plasma protein Þ bound (protein-free) bilirubin (bilirubin glucuronide)

indirect

Intestine (stercobilin (90%) a small part bypasses the liver and mesobilin (10%))Þ

OS with feces (dark coloring of feces)

Kidneys (urobilinogen (orange-red pigment))

OS with urine (yellow color of urine)

Oxidation in the light

Urobilin

Jaundice (lat. Jeterus) is a symptom of damage to the liver or bile ducts, manifested by a yellow discoloration of the skin and mucous membranes. This is due to the deposition of bile pigments in the tissues.

Depending on the origin, there are 3 types of jaundice: mechanical, parenchymal and hemolytic.

1. Mechanical (obstructive, congestive) jaundice.

It occurs as a result of difficulty or cessation of the outflow of bile from the liver into the duodenum.

Scheme 2. Obstructive jaundice.

Bile, accumulating and having no outlet. It breaks the bile capillaries and fills the hepatocytes, causing their death. Pouring into the lymphatic crevices and entering the general circulation, bile causes the phenomenon of cholemia. In addition, bilirubinemia and bilirunucria occur. The feces become discolored because... there is no flow of bile into the intestines. Bile, entering organs and tissues, causes jaundice and skin itching, as well as depression of the central nervous system. As a result of the death of hepatocytitis, obstructive jaundice can cause parenchymal jaundice.

2. Parenchymal (hepatic, infectious-toxic) jaundice.

Observed in a number of infections (Botkin's disease (viral hepatitis), pneumonia, typhus) and many poisonings that cause the death of liver cells.

Scheme 3. Parenchymal jaundice.

Red blood cells (90 – 130 days)	aging		(hemoglobin Þ bilirubin) Þ
Blood (free bilirubin) ß liver (a lot of free bilirubin Ü Organ damageÞ little bound bilirubin)

Parenchymal jaundice causes not only functional, but also morphological changes in hepatitis.

Therefore, not only pigment metabolism is disrupted, but also other types of metabolism, as well as the antitoxic and barrier functions of the liver. Bilirubinemia, bilirubinuria and urobilinuria are noted. As a result of intrahepatic blockage, symptoms of obstructive jaundice appear.

3. Hemolytic jaundice.

Scheme 4. Hemolytic jaundice.

Red blood cells (destruction)			(a lot of hemoglobin Þ a lot of bilirubin) Þ
Blood (lots of free bilirubin) ÞÞÞÞÞÞÞÞÞÞÞ

With hemolytic jaundice, only pigment metabolism is disrupted, because bile acids and cholesterol do not accumulate in the blood. This type of jaundice is characterized by bilirubinemia, urobilinuria and an increase in the amount of conjugated bilirubin in the blood. It is not excreted by the kidneys and is a toxin that subsequently causes damage to liver cells. This can lead to paremchymatous jaundice.

1. Cholelithiasis.

This disease is characterized by the formation of stones in the bile ducts of the liver and gallbladder. Causes: stagnation of bile, infection and disruption of nervous regulation. The main clinical manifestations are pain, jaundice and fever. The disease most often occurs in domestic animals (dogs, cats) and is associated with feeding.

Pathogenesis: the disease develops in one of two ways:

1) inflammation of the mucous membrane of the ducts or bladder Þ desquamation of the mucosal epithelium Þ
Þ layering of bile salts Þ stone.

2) stagnation of bile Þ its thickening as a result of reverse absorption of liquid Þ precipitation of salts in the form of sand Þ concentration of sand in stones.

The growth of stones occurs similar to the growth of a snowball, so when cut, the stones are usually layered. The stones contain inorganic and organic components of bile: bile pigments, bile salts and cholesterol. Stones may not cause visible harm or cause concern until they block the lumen of the bile ducts, often causing obstructive jaundice. The pain is caused by the pressure of the stone on the wall of the bile duct or gallbladder as a result of pressure from internal organs. A gradual thinning of the bladder wall develops and ultimately its perforation, which leads to inflammation of the peritoneum (peritonitis).

Fever occurs as a result of aseptic inflammation or infection.

The physiological significance of the liver as a gland involved in interstitial metabolism is determined by the fact that substances absorbed from the intestine into the blood pass through the liver and undergo chemical changes in it. In the liver, glucose is formed from a number of substances (fructose, galactose, lactose, glycerol, amino acids), from which glycogen is synthesized and deposited in the liver cells (see Carbohydrate metabolism). In the liver, acetone bodies are formed from lipids (mainly due to a lack of glycogen in the liver and diabetes), most of the cholesterol, bile acids, and carotene also accumulates. Here, deamination and transamination of amino acids occurs (see Nitrogen metabolism), blood proteins (albumin, globulins, many blood clotting factors), urea, uric acid, choline, and creatinines are synthesized. A significant part of hemoglobin is destroyed in the liver; the resulting bilirubin (see) is excreted with bile into the intestines, iron (ferritin) is deposited.

The liver takes part in maintaining the dynamic balance of many plasma substances (sugar, cholesterol, blood proteins, axerophthol, iron, water). About 1.5 liters of blood flows through the liver in 1 minute. and 1/7 of the body’s total energy is released in it. The temperature of the blood flowing from it during digestion increases by 1-2°.

To study the functions of the liver, they resort to removing it, turning off the portal blood flow, applying angiostomy tubes to the vessels, and perfusion of the isolated liver. After removal of the liver, 3-8 hours. hypoglycemia occurs (see), leading to death.

To study the participation of liver cells and vessels in the transformation of substances that enter the blood in one way or another, various options for vascular ligation are used, including direct and reverse Eck-Pavlov fistulas, ligation of the hepatic artery and all afferent vessels of the liver (devascularization). The Eck-Pavlov fistula operation involves creating an anastomosis between the portal and inferior vena cava.

After such an operation and ligation of the portal vein near the liver, all blood from the intestines begins to enter the body, bypassing the liver. At the same time, the viability of the liver is preserved, since its blood supply is preserved: blood enters through the hepatic artery and flows out through arteriovenous and arterio-sinusoidal anastomoses (Fig. 8).

Rice. 8. Scheme of relationships between intrahepatic vessels:
1 - arteries;
2 - bile duct;
3 - lymphatic duct;
4 - branch of the portal vein;
5 - central foam;
6 - liver cells;
7 - bile canaliculus;
8 - Disse space;
9 - sinusoid;
10 - Kupffer cells;
11 - entrance sphincter;
12 - exit sphincter;
13 - arteriovenous anastomosis;
14 - arteriole flows into the sinusoid.

In the blood of the portal vein during the digestion process, the amount of ammonia, glucose, amino acids, and water increases sharply. In the presence of an Eck's fistula, blood of such a composition enters the circulation, as a result of which the amount of ammonia sharply increases in the blood and brain tissue with a high protein content in food, poisoning develops, and the animal goes into coma. In the liver, ammonia is converted into a less biologically active substance - urea, and substances such as histamine, digitalis, novocaine, iron, atropine, ergotoxin, morphine and others, to some extent lose their toxicity. When the hepatic artery is ligated, collaterals develop over time, which partially ensures the delivery of arterial blood.

The liver continues to take part in metabolic processes even after staged devascularization. The level of sugar and cholesterol in the blood is maintained, serum albumin is slightly reduced.

The liver inactivates many hormones: adrenaline, estrogens, gonadotropic hormones, adrenal hormones, secretin, gastrin, etc. Along with neutralization, some substances, passing through the liver, on the contrary, acquire greater toxicity, for example, colchicine turns into a more toxic substance - oxycolchicine; After acetylation in the liver, sulfonamides become less soluble, as a result of which they are easily deposited in the urinary tract.

In the implementation of the protective function against foreign agents, reticuloendothelial (Kupffer, “shore”) cells play a significant role. They have the properties of fixed phagocytes that absorb bacteria from the blood, as well as some irritating substances. Phagocytic activity is favored by slow blood flow in the portal sinusoids. However, these cells can also play a negative role, absorbing and retaining for a long time many substances, for example, gum arabic, polyvinylpyrrolidone, which are part of plasma substitutes. As a result of the accumulation of a large amount of irritating substances, reactive proliferation of Kupffer cells occurs, which leads to a cirrhotic process.

The liver has a bile-forming function, which is largely excretory. Bile (see) contains many substances that circulate in the blood (dyes, antibiotics, bilirubin, hormones), as well as substances formed in the gland itself, for example bile acids, which form paired compounds with glycocol and taurine (glycocholic and taurocholic acids), which gives them greater solubility. Possessing high surface activity, they sharply reduce the surface tension of bile, and this helps to retain a number of substances in it in a dissolved state (cholesterol, lecithin, calcium salts). In the intestine, bile acids help emulsify and absorb fat (see Fat metabolism); 85-95% of bile acids are absorbed from the intestine into the blood, from where they are captured by liver cells and again excreted into bile. In this way, the enterohepatic circulation of bile acids is established.

Kupffer and polygonal cells take part in the process of bile formation. There is a direct connection between the blood vessels and the bile canaliculi: the sinusoids communicate through the intercellular gaps with the spaces of Disse, and the latter connect to the bile canaliculi through the pores between the liver cells. Blood substances can penetrate the bile canaliculi in two ways: through the intercellular spaces and through Kupffer cells.

Polygonal liver cells also participate in the process of bile formation, as evidenced by inclusions in the protoplasm containing proteins and bile pigments; In their formation, the Golgi apparatus apparently plays a significant role. It is possible that these same cells secrete water.

The leading role in the mechanism of bile formation is played, in all likelihood, by active transport of substances. This is evidenced by a number of facts: bile formation can occur at low blood pressure, and also in the case when the pressure of bile in the tubules is greater than the pressure of blood in the capillaries; removal of certain substances selectively (for example, sugar enters the blood and bile acids into bile); Bile formation sharply decreases against the background of inhibition of tissue respiration of the liver.

Some researchers believe that the primary process of bile formation occurs through the secretion of water and salts, dyes, and pigments dissolved in it. Subsequently, as it moves through the tubules, an equilibrium is established between substances that can penetrate the membranes, and all other substances that do not penetrate the membranes are retained in the bile. The latter can enter the blood only if the outflow of bile is disrupted.

The process of bile formation is affected by the influence of humoral stimuli: secretin, cholic acid salts, bile acids, acetylcholine, protein digestion products (peptones), hormones (adrenaline, thyroxine, sex hormones, ACTH, cortina). Nervous influences on the process of bile formation are not always expressed equally. The effect of irritation of the vagus nerves after their transection is different. The secretory effect is observed when they are irritated only on the 4-5th day after transection, which, according to the ideas of I.P. Pavlov, is associated with a more rapid degeneration of inhibitory fibers. Atropine under these conditions reduces the secretory response. Increased bile formation was also observed after irritation of the central end of the vagus nerve, provided that the other end was intact. Irritation of the sympathetic nerve apparently inhibits bile secretion.

The difficulty in elucidating the mechanism of action of nerves on the process of bile formation is that it is still unknown how this influence is carried out: either the nerves act directly on secretory cells, or the permeability of the membranes changes, or some vasomotor changes occur.

The process of bile formation is usually studied by collecting bile directly from the gallbladder. The amount of bile varies significantly under experimental conditions. It has been established that chronic loss of bile leads to a decrease in bile formation, and after feeding, bile secretion increases, especially in cases where, in addition to food, bile is introduced into the intestine. It has also been shown that bile from the duct enters the intestine continuously; its quantity, both in the presence and absence of a bubble, remains constant (A.V. Gubar).

An equally important function of the liver is blood storage. The liver vessels can hold 20% of all blood. Blood retention in the liver does not mean venous stagnation. The process of blood deposition in the liver is greatly facilitated by the sphincters of the veins and sinusoids. The input sphincter of the sinusoid regulates the inflow, and the output sphincter regulates the outflow of blood. Significant blood deposition is observed during anesthesia. The liver, as one of the depositing organs in the portal vein system, is a special “gateway” between the portal and general circulation. The activity of other depositing organs (spleen, intestines) depends on its functional state. All blood leaving the spleen and intestines necessarily passes through the liver.

The liver removes excess water from the blood, which goes into the formation of lymph and bile. The liver produces from 1/2 to 1/3 of all lymph with a high protein content (6%), as well as an average of 600-700 ml of bile per day, which is poured into the digestive tract. Blood flowing through the sinusoids loses a large amount of water, especially during digestion. During the period when blood flow into the portal vein increases, the pressure in it increases and becomes significantly higher than in the hepatic vein. In animals with portocaval anastomosis according to Eck, water introduced into the body in the form of an isotonic saline solution is excreted much more slowly.

The liver is a multifunctional organ. It performs the following functions:

• 1. Participates in protein metabolism. This function is expressed in the breakdown and rearrangement of amino acids. Amino acids are processed in the liver with the help of enzymes. The liver contains reserve protein, which is used when protein intake from food is limited.
• 2. The liver is involved in carbohydrate metabolism. Glucose and other monosaccharides entering the liver are converted into glycogen, which is stored as a sugar reserve. Lactic acid and the breakdown products of proteins and fats are converted into glycogen. When glucose is consumed, glycogen in the liver is converted into glucose, which enters the blood.
• 3. The liver participates in fat metabolism through the action of bile on fats in the intestines. Oxidation of fatty acids occurs in the liver. One of the most important functions of the liver is the formation of fat from sugar. With an excess of carbohydrates and proteins, lipogenesis (synthesis of lipoids) predominates, and with a lack of carbohydrates, gliconeogenesis (synthesis of glycogen) from protein predominates. The liver is a fat depot.
• 4. The liver is involved in the metabolism of vitamins. All fat-soluble vitamins are absorbed from the intestinal wall only in the presence of bile acids secreted by the liver. Some vitamins are deposited (retained) in the liver.
• 5. The liver breaks down many hormones: thyroxine, aldosterone, blood pressure, insulin, etc.
• 6. The liver plays an important role in maintaining the hormonal balance of the body due to its participation in hormone metabolism.
• 7. The liver is involved in the exchange of microelements. It affects the absorption of iron in the intestines and deposits it. The liver is a depot of copper and zinc. It takes part in the exchange of manganese, cobalt, etc.
• 8. The protective (barrier) function of the liver is manifested in the following. First, microbes in the liver undergo phagocytosis. Secondly, liver cells neutralize toxic substances. All blood from the gastrointestinal tract through the portal vein system enters the liver, where substances such as ammonia are neutralized (converted into urea). In the liver, toxic substances are converted into harmless paired compounds (indole, skatole, phenol).
• 9. The liver synthesizes substances that participate in blood clotting and components of the anticoagulant system.
• 10. The liver is a blood depot.
• 11. The participation of the liver in the digestive processes is ensured mainly by bile, which is synthesized by liver cells and accumulates in the gallbladder. Bile performs the following functions in the digestive processes:
  • * emulsifies fats, thereby increasing the surface area for their hydrolysis by lipase;
  • * dissolves fat hydrolysis products, thereby promoting their absorption;
  • * increases the activity of enzymes (pancreatic and intestinal), especially lipases;
  • * neutralizes acidic gastric contents;
  • * promotes the absorption of fat-soluble vitamins, cholesterol, amino acids and calcium salts;
  • * participates in parietal digestion, facilitating the fixation of enzymes;
  • * enhances the motor and secretory function of the small intestine.
• 12. Bile has a bacteriostatic effect - it inhibits the development of microbes, prevents the development of putrefactive processes in the intestines.

Some diseases of the digestive system

Chronic gastritis is manifested by chronic inflammation of the mucous membrane (in some cases, deeper layers) of the stomach wall. A very common disease, accounting for about 35% of digestive diseases, and 80-85% of stomach diseases.

Chronic gastritis is the result of the further development of acute gastritis, but more often develops under the influence of various harmful factors (repeated and prolonged eating disorders, consumption of spicy and rough foods, addiction to very hot foods, poor chewing, dry food, consumption of strong alcoholic beverages).

The cause of chronic gastritis can be poor nutrition (especially deficiency of protein, iron and vitamins), prolonged uncontrolled use of medications that have an irritating effect on the gastric mucosa (including some antibiotics), industrial hazards (lead compounds, coal, metal dust and etc.), the effect of toxins in infectious diseases, hereditary predisposition.

Under the influence of prolonged exposure to harmful factors, functional secretory and motor disorders of the stomach first develop, and subsequently dystrophic and inflammatory changes and disturbances in regeneration processes. These structural changes develop primarily in the epithelium of the superficial layers of the mucous membrane, and later the gastric glands are involved in the pathological process, which gradually atrophy.

The most common symptoms are a feeling of pressure and fullness after eating, heartburn, nausea, sometimes dull pain, decreased appetite, and an unpleasant taste in the mouth. Chronic gastritis with normal and increased secretory function of the stomach - usually superficial or with damage to the gastric glands without atrophy; occurs more often at a young age, mainly in men. Characterized by pain, often ulcer-like, heartburn, sour belching, a feeling of heaviness after eating, and sometimes constipation. Chronic gastritis with secretory insufficiency is characterized by atrophic changes in the gastric mucosa and its secretory insufficiency, expressed to varying degrees; develops mainly in mature and elderly people. Gastric and intestinal dyspepsia are noted (unpleasant taste in the mouth, loss of appetite, nausea, especially in the morning, belching of air, rumbling and transfusion in the abdomen, constipation or diarrhea); with a long course - weight loss. Possible complications: bleeding.

Chronic gastritis is considered a precancerous disease. Treatment is usually carried out on an outpatient basis; in case of exacerbations, hospitalization is advisable. Medical nutrition is of key importance. During the period of exacerbation of the disease, meals should be fractional, 5-6 times a day. Astringent and enveloping agents are indicated. In order to influence the secretory function of the stomach, vitamins PP, C, B6 are prescribed.

Prevention. The main importance is a balanced diet, avoidance of strong alcoholic beverages and smoking. It is necessary to monitor the condition of the oral cavity, promptly treat diseases of other abdominal organs, and eliminate occupational hazards. Patients with chronic gastritis should be registered at a dispensary and comprehensively examined at least twice a year.

Chronic cholecystitis is chronic inflammation of the gallbladder. The disease is common, more common in women. Bacterial flora (Escherichia coli, streptococci, staphylococci, etc.) penetrates the gallbladder. A predisposing factor in the occurrence of cholecystitis is stagnation of bile in the gallbladder, which can be caused by gallstones, compression and kinks of the bile ducts, disturbances in the tone and motor function of the biliary tract under the influence of various emotional stress, endocrine and autonomic disorders, reflexes from pathologically altered organs of the digestive system.

Stagnation of bile in the gallbladder is also promoted by pregnancy, a sedentary lifestyle, rare meals, etc. The direct impetus for an outbreak of the inflammatory process in the gallbladder is often overeating, especially the intake of very fatty and spicy foods, the intake of alcoholic beverages, an acute inflammatory process in another organ (sore throat, pneumonia, etc.).

Chronic cholecystitis can occur after acute cholecystitis, but more often it develops independently and gradually, against the background of cholelithiasis, gastritis with secretory insufficiency, chronic pancreatitis and other diseases of the digestive system, obesity.

Characterized by a dull, aching pain in the right hypochondrium that is constant or occurs 1-3 hours after eating a large and especially fatty and fried meal. The pain moves up to the area of ​​the right shoulder and neck, right shoulder blade. Bacteriological examination of bile (especially repeated) makes it possible to determine the causative agent of cholecystitis.

During cholecystography, a change in the shape of the gallbladder is noted, often its image is unclear due to a violation of the concentrating ability of the mucous membrane, sometimes stones are found in it.

After taking an irritant - cholecystokinetics (usually two egg yolks) - insufficient contraction of the gallbladder is noted. Signs of chronic cholecystitis are also determined by echography (in the form of thickening of the walls of the bladder, its deformation, etc.).

The course in most cases is long-term, characterized by alternating periods of relief and exacerbation; the latter often occur as a result of eating disorders, drinking alcohol, heavy physical work, and hypothermia. Deterioration of the general condition of patients and temporary loss of their ability to work - only during periods of exacerbation of the disease.

Depending on the characteristics of the course, there are sluggish and the most common - recurrent, purulent-ulcerative forms of chronic cholecystitis. Often the inflammatory process is the “impetus” for the formation of gallstones.

During exacerbations of chronic cholecystitis, patients are hospitalized in surgical or therapeutic hospitals. In mild cases, outpatient treatment is possible. Prescribe bed rest, dietary nutrition, with meals 4-6 times a day, antibiotics by mouth. During the period of subsidence of the inflammatory process, thermal physiotherapeutic procedures can be prescribed to the area of ​​the right hypochondrium (UHF, etc.).

To improve the outflow of bile from the gallbladder, both during exacerbation and during remissions, choleretic drugs are widely prescribed: allohol and a decoction or infusion of corn silk. These drugs have antispasmodic, choleretic, nonspecific anti-inflammatory and diuretic effects. Chronic cholecystitis is treated with mineral water (Essentuki No. 4 and No. 17, Slavyanovskaya, Smirnovskaya, Mirgorodskaya, Novo-Izhevskaya, etc.). After the exacerbation of cholecystitis subsides and for the prevention of subsequent exacerbations (preferably annually), sanatorium-resort treatment is indicated (Essentuki, Zheleznovodsk, Truskavets, Morshin and other sanatoriums, including local ones, intended for the treatment of cholecystitis).

Prevention of chronic cholecystitis consists of following a diet, playing sports, physical education, preventing obesity, and treating focal infections.

Intestinal dysbiosis is a disease characterized by a violation of the mobile balance of microflora that normally populates the intestines. If in healthy people lactobacilli, anaerobic streptococci, E. coli, enterococci and other microorganisms predominate in the sections of the small intestine and large intestine, then with dysbacteriosis the balance between these microorganisms is disturbed, putrefactive or fermentative flora and fungi develop abundantly. Microorganisms that are normally uncharacteristic for it are found in the intestines. Opportunistic microorganisms are actively developing, usually found in small quantities in the intestinal contents; instead of non-pathogenic strains of Escherichia coli (Escherichia), its more pathogenic strains are often found. Thus, with dysbiosis, qualitative and quantitative changes in the composition of microbial associations in the gastrointestinal tract (microbial landscape) are observed.

Intestinal dysbiosis is caused by diseases and conditions that are accompanied by disruption of the processes of digestion of nutrients in the intestine (chronic gastritis, chronic pancreatitis, etc.). The cause of intestinal dysbiosis can be long-term, uncontrolled use of antibiotics, especially broad-spectrum antibiotics, which suppress the normal intestinal flora and promote the development of those microorganisms that are resistant to these antibiotics.

With dysbacteriosis, the activity of the intestinal microflora against pathogenic and putrefactive microorganisms is disrupted. Products of abnormal breakdown of nutrients by microflora unusual for the intestine (organic acids, hydrogen sulfide, etc.), formed in large quantities, irritate the intestinal wall. It is also possible to develop an allergy either to normal breakdown products of food substances or to bacterial antigens.

Characteristic: decreased appetite, unpleasant taste in the mouth, nausea, flatulence, diarrhea or constipation. Signs of general poisoning are often observed, lethargy is observed, and ability to work is reduced. When diagnosing, one should distinguish between dysbacteriosis that occurs against the background of irrational use of antibacterial drugs and dysbacteriosis that accompanies acute and chronic diseases of the digestive system.

Treatment in mild cases is outpatient, in more severe cases - in an inpatient setting. Stop the administration of antibacterial agents, which could lead to the development of dysbacteriosis, and prescribe restorative therapy (vitamins, etc.). To normalize the intestinal flora, it is advisable to use enteroseptol and bifidumbacterin. It is often advisable to prescribe digestive enzyme preparations.

Prevention comes down to the rational prescription of antibiotics, good nutrition and restorative therapy for people who have suffered from severe general diseases of the digestive system.

Functional gastric achylia is a condition characterized by temporary inhibition of gastric secretion without organic damage to the secretory apparatus of the stomach.

Causes: depression, poisoning, severe infectious disease, hypovitaminosis, nervous and physical fatigue, etc. Apparently, in some people functional achylia is associated with congenital weakness of the secretory apparatus of the stomach. Functional achilias are observed in patients with diabetes mellitus. Typically, functional achylia is a temporary condition.

However, with prolonged inhibition of the neuroglandular apparatus of the stomach, organic changes develop in it.

The disease is asymptomatic or manifests itself as a decrease in appetite, in rare cases - poor tolerance of certain types of food (milk), and a tendency to diarrhea. A distinction is made between achlorhydria (the absence of free hydrochloric acid in the gastric juice) and achylia, in which there is also no pepsin in the gastric juice.

Treatment. It is necessary to eliminate the factors leading to the development of functional achylia. For neurogenic achilia, a work-rest schedule, regular meals are established, and juice substances, vitamins, and bitters are prescribed.

The liver is the largest glandular organ, and if removed or severely damaged, death occurs in a person or animal.

Main functions of the liver:

• 1) synthesis and secretion of bile;
• 2) participation in the metabolism of carbohydrates, fats and proteins (deamination, synthesis of amino acids, urea, uric and hippuric acids);
• 3) fibrinogen formation;
• 4) formation of prothrombin;
• 5) formation of heparin;
• 6) participation in the regulation of total blood volume;
• 7) barrier function;
• 8) hematopoiesis in the fetus;
• 9) deposition of iron and copper ions;
• 10) formation of vitamin A from carotene.

Insufficiency of liver function in the body is manifested in metabolic disorders, bile formation disorders, decreased liver barrier function, changes in the composition and properties of blood, changes in the function of the nervous system, and impaired water metabolism.

LIVER FAILURE

Etiology of liver failure

Among the large number of etiological factors that lead to liver failure, the most important are the factors that cause inflammation in the liver - hepatitis. These include bacteria (streptococcus, staphylococcus, typhoid bacillus, etc.), viruses, spirochetes, industrial poisons (phosphorus, mercury, lead, manganese, benzene, etc.), medicinal substances (barbiturates, sulfonamides, atophan, antibiotics - biomycin, tetracycline), plant poisons, alkaloids, etc.

With parenteral administration of foreign protein, serums, vaccines, food and drug allergies, allergic hepatitis can develop.

Often, insufficiency of liver function occurs due to long-term dietary disturbances (consumption of fatty foods, alcoholic beverages, lack of protein in food). The final stage of development of chronic hepatitis is usually cirrhosis of the liver. Histologically, cirrhosis is characterized by degenerative changes in liver cells with simultaneous atypical regeneration and strong proliferation of connective tissue, resulting in either scar formation or diffuse shrinkage of the liver.

Liver function disorders can be of a secondary nature, for example, in case of impaired general circulation, impaired bile secretion, or general amyloidosis.

Experimental reproduction of liver failure

Complete liver removal. The operation of complete liver removal in dogs is performed in two steps. First stage consists of anastomosis between the inferior vena cava and the portal veins, followed by ligation of the inferior vena cava above the anastomosis. Second phase : 4-5 weeks after the development of collaterals that ensure the outflow of venous blood into the superior vena cava, the portal vein is ligated above the anastomosis and the liver is removed. 3-8 hours after liver removal in dogs, symptoms of hypoglycemia occur (first phase). This condition can be temporarily improved by administering 0.25-0.5 g/kg glucose or fructose intravenously every hour (Fig. 103).

Removal of the liver also leads to a decrease in urea in the blood and urine, an increase in amine nitrogen and uric acid in the blood, a decrease in albumin, fibrinogen, prothrombin in the blood serum, an increase in all amino acids and bilirubin in it, which gives an indirect reaction. The antitoxic function of the liver is lost.

Poisoning the body with toxic products causes a coma after 20-40 hours, ending in death from paralysis of the respiratory center. Before this, the animal experiences periodic breathing of the Cheyne-Stokes type, tachycardia, and a decrease in blood pressure (second phase).

Partial liver removal. After removing 70-75% of the liver in dogs or rats, after 4-8 weeks, its original weight is completely restored. Restoration of the organ is two-phase. The most rapid weight gain is observed during the first 3 days after surgery, which is associated with a period of intense division of liver cells. The second phase of liver weight gain is observed from the 7th day and is caused by cell hypertrophy. During the regeneration process, a change in metabolism occurs. The glycogen content in the liver sharply decreases in the first hours after partial removal. During the same period, glucose utilization decreases, as the activity of hexokinase and glucokinase drops to 50% of the norm.

In the regenerating liver, the activity of transaminases, arginase and other enzymes noticeably decreases. The most dramatic changes are observed in the metabolism of nucleic acids. The period starting from 12 hours after liver removal and lasting up to 3 days is characterized by intense synthesis of DNA and RNA.

Partial removal of the liver can be repeated several times without reducing the ability to regenerate and without losing its main functions.

Eck fistula placement. In order to establish the significance of insufficiency of liver functions in the processes of digestion and interstitial metabolism, in 1877 the Russian surgeon N.V. Eck proposed the operation of anastomosis between the portal and inferior vena cava (Fig. 104). The portal vein above the anastomosis is ligated and thus the liver is switched off from the vascular system of the digestive organs.

In the first days after the operation, the condition of the animals, provided they are fed dairy and plant foods, is satisfactory, despite the fact that blood flow through the liver and oxygen consumption are reduced by 50%. After 10-12 days, movement disorders (ataxia, manege movements), rigidity of the hind limbs, tonic and clonic convulsions appear and increase. Along with this, symptoms of depression and drowsiness are detected. The animal reacts poorly to painful stimuli. When feeding raw meat, the described phenomena occur within 3-4 days after the operation. The content of ammonia and ammonium salts in the blood increases significantly, which under normal conditions are neutralized by the liver. After the application of an Eck fistula, the liver’s ability to regenerate decreases, the synthesis of proteins and hemoglobin, the use of amino acids, the synthesis of bile acids and other functions decrease.

Fistula Pavlova - Ecca(reverse Eck fistula). An anastomosis is placed between the inferior vena cava and the portal vein, followed by ligation of the inferior vena cava above the anastomosis. The purpose of this operation is to be able to study liver functions under different conditions of food load and determine its detoxification role in the body.

Angiostomy in London. In dogs, cannulas are sewn into the wall of large veins (portal and hepatic), making it possible to chronically receive blood flowing to the liver and flowing out of it. Using this method, it was possible to study the participation of the liver in various disorders of interstitial, protein, carbohydrate, salt metabolism and bilirubin formation. The angiostomy method also makes it possible to obtain experimental data on the barrier and neutralizing functions of the liver.

Liver puncture and scanning. To determine the condition of the liver, the intravital puncture method is currently used. A suspension of cellular elements or a small cylindrical piece of liver tissue is examined, from which sections are prepared for microscopy, which makes it possible to judge the morphological and histochemical changes in the liver with its various lesions.

Radioisotope method Liver examination involves the use of rose bengal paint labeled J 131. Normal liver epithelial cells selectively absorb this dye. When the function of the liver parenchyma changes (hepatitis, cirrhosis, development of tumor nodes), paint absorption is disrupted and characteristic defects are visible on the scanogram (absorption curve).

Metabolic disorders due to liver failure

Carbohydrate metabolism. When the liver parenchyma is damaged, the following processes occur:

• 1) reducing the formation and deposition of glycogen in the liver from monosaccharides and their breakdown products;
• 2) inhibition of glycolysis;
• 3) inhibition of gluconeogenesis - the formation of glucose from the breakdown products of protein and fat;
• 4) a decrease in the flow of glucose into the general circulation and the development of hypoglycemia. A drop in blood sugar levels below 45-40 mg% can lead to hypoglycemic coma.

Fat metabolism. Disorders of fat metabolism are expressed as follows:

• 1) stopping the release of triglycerides and fatty acids from the liver as part of lipoproteins;
• 2) a violation of fat oxidation in the liver, which causes its fatty and infiltration;
• 3) increased formation of ketone bodies;
• 4) changes in cholesterol synthesis (see “Disorders of fat metabolism”).

Protein metabolism. The causes of protein metabolism disorders are:

• 1) disruption of the synthesis of protein and other nitrogen-containing substances (choline, glutathione, taurine, ethanolamine) from amino acids;
• 2) changes in the breakdown of amino acids in the reactions of deamination, transamination, decarboxylation;
• 3) violation of urea formation.

Protein synthesis disorder is one of the first signs of liver failure. The result of this may be a qualitative and quantitative change in the composition of blood plasma proteins. At the very beginning, when the liver parenchyma is damaged, abnormal, qualitatively altered paraprotein globulins appear. More significant disorders of liver function lead to a decrease in albumin, α- and β-globulins, since the liver under normal conditions synthesizes all blood albumin and about 80% of globulins. The exception is γ-globulin, the synthesis of which occurs in lymphatic tissue and bone marrow. When the liver is damaged, the synthesis of fibrinogen and prothrombin also decreases and their content in the blood decreases.

Impaired breakdown of amino acids, as well as protein biosynthesis, occurs as a result of a decrease in ATP and pyridine nucleotides in the liver cell when the liver parenchyma is damaged. In this case, the main pathway of amino acid breakdown - oxidative deamination - to α-keto acids and ammonia through intermediate stages suffers. Damage to the liver parenchyma also disrupts transamination processes. Due to this, the synthesis of amino acids and, at the same time, proteins are reduced.

The main method of neutralization and removal of ammonia in mammals is the formation of urea, which occurs in liver cells (ornithine cycle). The formation of citrulline occurs in mitochondria, and the formation of arginine occurs in the cytoplasmic matrix. This process requires the necessary amount of energy and appropriate enzymes. Therefore, with damage to the liver parenchyma and a decrease in ATP, an increase in ammonia and amine nitrogen in the blood and a decrease in urea and uric acid in the blood and urine are observed. Retention of ammonia in the body leads to toxic effects, especially from the central nervous system.

A decrease in protein synthesis dramatically changes the activity of various enzymes: cathepsins, esterases, etc., since a significant part of the liver protein is an enzymatic protein.

Impaired liver barrier function

Insufficiency of liver function is also characterized by a violation of its barrier function. Experiments conducted on dogs with Eck's fistula confirmed that the liver neutralizes toxic products resulting from protein metabolism. In such dogs, ammonium carbamate and methylated betaine products can be found in the body.

The neutralizing function of the liver is achieved thanks to the chemical processes occurring in it. The most important of them are the following:

Acetylation. This process occurs with the help of coenzyme A with the participation of ATP. In this case, along with non-toxic compounds, some toxic products can also be formed. Once acetylated in the liver, sulfonamides become less soluble and more easily deposited in the urinary tract, which can lead to bleeding and anuria.

Oxidation. In liver failure, this process, like acetylation, is reduced. There is no oxidation of amino groups using amino oxidases to aldehydes and corresponding acids. This disrupts the conversion of santonin into oxysantonin, atophan into oxyatophan, and ethyl alcohol through acetaldehydes to acetic acid.

Methylation. It changes sharply with insufficiency of liver function, in particular the formation of adrenaline, creatine, methylnicotinamide from methyl groups, the donors of which are methionine, choline, betaine.

Formation of pair compounds. The formation of such compounds with glucuronic acid, glycocol, cystine and sulfuric acid is often reduced. For example, the synthesis of hippuric acid from glycocol and benzoic acid (Quick's test) is significantly reduced. The formation of aromatic acids and alcohols (phenol, benzoic and salicylic acids, phenolphthalein, menthol, camphor) in combination with glucuronic acid is also reduced. The formation of paired compounds with cysteine ​​and the formation of mercapturic acids are reduced. The formation of indican from indole sharply decreases when it is combined with sulfuric acid.

Damage to the cells of the reticuloendothelial system of the liver leads to disruption of the retention, digestion and neutralization of many microorganisms, their toxins and various colloidal compounds.