J.Jpn. Surg. Soc.. 55(7): 631-661, 1954
宿題報告
Clinical and Experimental Studies on Acute Intestinal Obstruction
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Surgery, Nippon Medical School Saburo MATSUKURA |
Pathophysiology of lieus
(1) Immunoserological studies
1. The percipitation test revealed that the lipoprotein of the intestine of normal and ileus animals can produce highly specific antibodies.
2. Intensity of Arthus phenomenon of the rabbits sensitized to the antigens of men and of animals differs but little. The fact deserves attention.
3. Injection of these antigens into guinea pigs causes weak active anaphylactic shock, while the serum injection of the rabbits sensitized to intestinal lipoprotein causes typical reversed anaphylactic symptoms (bronchial spasm, convulsions of extremities, defecation, urination, etc.), and kills guinea pigs.
These phenomena are immunologically important, for they indicate the presence there of some common antigen in the intestinal lipoprotein and in the organs of guinea pigs ; hence further experiments on this point.
Experiment I. Antigen adsorption test
The mixture of this antiserum and a large quantity of intestinal lipoprotein does not let the animals die, although the antiserum alone give rise to shock death.
Experiment II. Desensitization
Desensitization of guinea pigs is not effective after several injections of the antiserum.
Experiment III. Study on antigenic specificity of organ lipoprotein
Complement fixation test reveals that there is a common antigen in the lipoprotein of many organs.
These results show that in ileus, antigen-antibody reaction occurs not only in bowels but also in many organs.
4. Relations of intestinal lipoprotein with Forssman antigen.
Experiment I. Injection of the serum of the rabbits sensitized to intestinal lipoprotein causes relatively demonstrative shock symptoms to mice and rats that have had no Forssman antigen ; but not death.
Experiment II. This antiserum reacts slightly with Forssman antigen in the complement fixation test.
Experiment III. This antiserum has a little hemolysin a s has been revealed in the test with the red cells of a goat.
Experiment IV. After adsorption of this antiserum with bacteria (Shigella shigae, Salmonella typhi) that contain Forssman antigen, this antiserum can bring guinea pigs reversed anaphylaxis and death.
These experimental data tell that the intestinal lipoprotein is similar but not quite identical to Forssman antigen.
5. Studies on the antigen of ileus
Experiment I. Two and a half hours after the onset of strangulation, the precipitation test is positive in the serum and the ascites of diseased animals.
Experiment II. The precipitation test of the serum remains positive several days after the release of obstruction, and the value reaches maximum 24 hours after the operation.
Experiment III. In the serum of the patients 24 hours after the opeation, the precipitation test is positive, but is negative 48 hours postopreatively.
Experiment IV. Studies on complement values in ileus Figures indicate that the complemental values decrease with the progress of ileus, suddenly reducing to zero as death sets in.
6. Studies on antibodies in ileus
Experiment I. Animal serum several hours after the onset of the obstruction is found positive in the precipitation test.
Experiment II. In the serum of the patients, 24 hours after the operation, the precipitation test is positive.
Summary : By the immunoserological studies mentioned above, the author now knows that anaphylactic shock develops in ileus by the antigen and antibody of the lipoprotein.
(2) Studies on vagus substance in ileus
1. The intestine of a guinea pig is very sensitive to histamine, and contracts intensively, but that of a mouse is not.
2. Pyribenzamine inhibits the contraction of a guinea pig's intestines.
3. By acetylcholine, the bowels of a mouse contracts as those of a guinea pig.
4. Marked contraction is inhibited by atropine.
5. The serum of healthy men and animals does not cause the contraction to the bowels of a guinea pig and of a mouse.
6. The serum in ileus contains an effective substance that causes the bowel ccntration to a guinea pig and a mouse.
7. This effective substance is not influenced by pyribenzamine, but inhibited by atropine.
8. If kept in an ice box for 24 hours, it becomes markedly inactive.
9. Addition of eserine to this substance does not alter its action after 24 hours.
10. Such an effective substance is proved in the ascites, several hours after the onset of the obstruction.
11. This substance is also proved in dogs treated with eserine earlier, and its quantity is larger than it is in untreated dogs.
12. The substance increases with the progress of ileus and even so after the release of the obstruction. It disappears from the serum several days after the releaese.
These taken into consideration, the increased effective substanse in the serum and ascites in ileus that is capable of contracting the intestines can be concluded to have the fhe tollowing characteristics.
1. It can contract not only the bowels of a guinea pig but also those of a mouse which is not sensitive to histamine.
2. This action is not influenced by pyribenzamine.
3. But is markedly inhibited by atropine. Accordingly the substance is very much like aectylcholine, and not histamine.
(3) Studies on Histamine
1. Histamine in the blood, the lung, the liver, and the bowels does not change in ileus.
2. In some closed loop of the bowels, histamine increases, but in others, it remains unincreased.
3. Antibiotics by way of mouth prevents the increase of histamine in the closed loop. This indicates that histamine in the bowels has intimate relations with intestinal bacteria.
Histamine in the ascites is almost equal to that in the blood quantitatively, and with the grade of bowel necrosis, it slightly increase.
(4) Studies on acetylcholine and cholinesterase in ileus
1. Acetylcholine of the intestine
The upper portion of the normal intestine contains more acetylcholine than the lower portion. In ileus, above the obstruction, acetylcholine remains unchanged, but below the obstruction, it is reduced, In the closed loop, its reduction is remarkable and is parallel to the pathological changes.
2. Acetylcholine of the liver
Acetylcholine is not found in the normal liver, but is seen much in the ileus liver.
3. Cholinesterase in the blood and liver in ileus
Cholinesterase is slightly less than in the normal blood, while it is one half of the normal value in the liver.
4. Deacetylcholinizing power of the liver
Perfusion method proves that the normal liver has highly deacetylcholinizing power, which, in ileus, reduces and goes in parallel to the activity of cholinesterase in the liver.
Influence of Ileus
1. On blood circulation
In the ileus shock the volume of the circulating blood reduces to 2/3 of the normal value, and that of the plasma, to one half. Extracellular fluid increases in the early stage of ileus, but reduces to 2/3 of the normal volume in the shock stage. In the shock stage liver blood flow and the pressure of the small veins of the liver are seen lessened. Renal blood flow and glomerular filtration are lowered.
2. Plasma protein and tissue protein
Blood specific gravity (GB) increases and plasma specific gravity (GP) decreases both to a marked degree. Here, the blood liquid and plasma protein give very much lowered readings, while albumin reduces much. But serum globulin, particularly γ-globulin increases.
Tissue protein
There is more mobile protein than visceral protein in the normai liver. In muscles, vice versa.
In the shock stage, however, hepatice mobile protein conspicuously lessen, while that of the muscles reduces but little. Visceral protein remains unchanged both in the liver and in muscles.
Liver fluid increases much in the shock stage, but musclar fluid reduces. There appear marked hemoconcentration and hypoproteinemia.
3. Intermediary protein metabolism
The increases of aminoacid nitrogen is very slow in the early stage of the disease, but becomes very rapid, particularly in the hepatic veins, as the shock stage is reached. Non-protein nitrogen in the blood is increased earlier than amino-acid nitrogen.
4. Blood gas, pH, and tissue respiration
In the shock stage, oxygen decrease and carbon dioxide increase are strong in the portal and hepatic veins, indicating poor blood supply and anoxia of the liver.
With the progress of the desease blood pH reduces in the hepatic veins.
Tissue respiraion of the liver increases in the early stage of ileus, but reduces in the shock stage.
5. Tissue glycogen
Blood glycogen and lactic acid. Liver-and muscular-glycogen increased in ileus. Blood glucose incre ases but in the shock stage it is inclined to decrease.
Blood lactic acid is increased, particulary in the hepatic veins.
6. Serum iron, tissue iron, and Ferritin fragment in ileus.
Serum iron increases.
Tissue iron and ferritin of the liver markedly reduced. Ferritin fragment appaers in the circulatory blood.
7. Urine 17 K.S. and blood acidphiles
17 Ketosteroids in the urine increase to a considerable extent, and three days after the release of obstruction they reach maximum. Acidophilic cells are low in number, but 5 days after the release of obstruction, they begin to return to the normal level.
8. Pathohistological studies
In the liver, as a result of circulatory disturbance, there occur congestions that are marked in the lobules and in the central zones. Edema and hemostasis develop. Regressive degenerations count atrophy of the cell chords of the liver, rarefaction, dissociation, turbid swelling, and nuclear concentration. Mitochondria is disintegrating and getting into the abnormal arrangement.
Kidneys show high grade hemorrhage into the cortex and medulla. The deposition of protein in the space of urinary tubles and Bowman capsules indicate renal insufficiency.
The adrenal cortex marks such degeneation of cells as pale staininig, fusion and disappearance of nucleus. Cellular infiltration and small necrotic dots indicate violent secretion.
Alkali phosphatase increases in the liver. But, in the intestine above the obstruction, it is unchanged, while in the part below the obstruction, it is reduced.
Ribonucleic acids and polysaccharides in the liver disintegrate with the progress of ileus, and it takes two days after the release of obstruction for them to return to the normal values. In the mesenteric lymph nodes there is prolifiration of the basophilic reticular cells in the early stage, and five days after the release, low-molecule desoxyribonucleic acids are found. In the adrenal cortex, lipoids and cholesterine are reduced.
9. Bacteriological Studies
a. Aerobic and anaerobic bacteaia in the bowels and ascites show remarkable proliferation as ileus progresses. Administration of antibiotics before obstruction inhibits bacterial growth in the bowel.
Animal experiments proved that those treated with antibiotics survive 5 times longer than the untreated animals do.
b. The great majority of intestinal bacteria is Colibacilli and produces indol in ileus.
c. More obligate anaerobes are isolated from the bowels of experimental animals and patients than from the normals.
d. Most anaerobes in the bowels are of bacillus type and are Gram positive.
e. Most bacteria which are isolated in ileus are B. welchii, B. ramosus, and B. bifidus.
f. In cases in which anaerobes are found, death comes earlier than in the case in which they are absent.
g. Chief gas producing anaerobes are B. welchii, B. ramosus, and Vibrion septique.
Clinic of Ileus
Diagnosis
It is not always easy to establish correct diagnosis in all cases of ileus. Causes vary, and also sites and types of the obstruction differ from one another. For instance, complicated ileus, clinical course is more acute than in the simple one. Volvulus of small intestine is rare and yet early diagnosis is desirable. The following table will help the easy diagnosis of this disease.
1. Shock symptoms are usually strong.
2. There are ileus symptoms (abdominal pain, vomiting, absence of excretion of gas and stools).
3. In most cases, distention of abdomen, visible peristalsis, loud whirring and gurgling sounds are not so marked as in the ordinary mechanical ileus.
4. Roentgenologic examination shows that in most cases there are no such symptoms as dilation of the bowel, gas accumulation, and fluid level. Authors call it "negative shadow" or "gas minus ileus".
5. Intraabdominal exsudate is mostly present.
6. Many patients have had a laparotomy.
7. There is leucocytosis.
8. There is no rise in temperature.
Treatment
The treatment of ileus has made a remarkable progress as the Knowledge of pathophysiology and antibiotics made early diagnosis and early treatment possible. According to the statistics of our clinic in the 15 years from 1935 to 1950, the operative mortality of ileus was 12.0 percent of 374 cases. Since 1951 up to the present, however, it reduced to 1.9 percent of 103 patients.
Conclusion
1. The most significant factor that brings death in ileus is anaphylactic shock caused by antigen-antibody reaction of the intestinal lipoprotein.
2. The effective substance in the blood of ileus is not histamine but acetylcholine-like substance.
(author's abstract)
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