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BREAST DISEASE     Breast cancer Breast lump Breast awareness Breast calcifications  Breast cysts Breast pain Duct ectasia Fat necrosis Fibroadenoma Hyperplasia Intraductal papilloma Phyllodes tumour Sclerosing adenosis                                                                                                                                                 

LIVER ABSCESS      Anatomy of liver Physiology of liver Method of examination of liver Haematology of liver disease. Amoebic liver abscess .Pyogenic liver abscess. Percutaneous needle aspiration of liver abscess. Case study.  Result Result continued  Discussion                                                                 

CHOLECYSTECTOMY    Introduction   Historical Review  Anatomy of Gallbladder Physiology of Gallbladder Physiologic effects of pneumoperitoneum Pathology  of Gallbladder Investigations Pre- operative preparation of laparoscopic cholecystectomy Contraindications  Treatment modalities for gallstones.  Anaesthesia                                                                                                                       

INGUINAL HERNIA    HOW SURGICAL OPERATION IS DONE     THYROID EXAMINATION MANAGEMENT OF SEVERELY INJURED PATIENT      SEPSIS AND MULTIPLE ORGAN FAILURE CHEST TRAUMA     BRONCHOGENIC CARCINOMA     TETANUS AND ANAEROBIC INFECTIONS 

PHYSIOLOGY OF GALLBLADDER.

INTRODUCTION:

            All the hepatic cells continually form a small amount of secretion called bile. This is secreted into a minute bile canaliculi that lies between the hepatic cells in the hepatic plates, and the bile then flows peripherally towards the interlobular septa where the canaliculi empty into terminal ducts, finally reaching the hepatic duct and common bile duct from which the bile either empties directly into the duodenum or is directed through the cystic duct into the gall bladder. The gall bladder and bile ducts are well adopted for the function of storing and discharging bile into the duodenum during digestion. The storage of bile in small bulk is made possible by the concentrating power of the gall bladder. The intermittent discharge of concentrated bile results from co-ordination between the gall bladder and the sphincter of the common bile duct, so that the contraction of the gall bladder is accompanied by the relaxation of the sphincter.

 

FUNCTIONS OF THE GALL BLADDER.

            The functions of gall bladder are as follows,

(A)  STORAGE OF BILE IN GALL BLADDER

(B)   GALL BLADDER ABSORPTION OR CONCENTRATION OF BILE

(C)  GALL BLADDER SECRETION

(D)  GALL BLADDER AND BILIARY TRACT MOTOR ACTIVITY

 

(A)  STORAGE OF BILE IN GALL BLADDER:

            The bile secreted continually by the liver cells is normally stored in the gall bladder until needed in the duodenum. The liver excretes bile at the rate estimated at 40 ml/hr. the total secretion of bile each day is some 700 to 1200 ml, and the maximum volume of the gall bladder is only 30 to 60 ml. Bile secretion that can be stored in gall bladder is 12 hours.

 

(B)   GALL BLADDER ABSORPTION OR CONCENTRATION OF BILE:

            A primary function of the gall bladder is to concentrate bile by absorption of water and sodium. It has been more than three hundred years since Diemerbroek first recognised that bile enters the gall bladder. In the early 1900s, it was suggested that the difference between the gall bladder and the hepatic bile could be explained by gall bladder absorption of isotonic NaCl and NaHCO₃. Subsequent studies by Radvin demonstrated that that the gall bladder reabsorbs approximately 16% of its volume per hour without any significant alteration in the amounts of bile acids, bile pigment, or cholesterol that are initially present ³⁰. These early investigators concluded that constituents of bile were neither absorbed nor secreted by the gall bladder, but increased in concentration as a result of an absolute decrease in gall bladder volume. The gall bladder is capable of concentrating the impermeable solutes contained in the hepatic bile by a factor of 5 to 10 and reducing its volume by 80-90%. Gall bladders transport large volumes of isotonic fluid. Despite a dramatic increase in sodium concentration, the presence of bile salts and proteins is responsible for the observation of gall bladder bile is isotonic to plasma. (Figure 8)

            Reabsorption of the gall bladder fluid is largely determined by the sodium transport. The cation traverses the apical (luminal) membrane down an electrochemical gradient. This relatively low cellular concentration is maintained by active Na⁺ extrusion across the basolateral membrane by an energy dependent carriers exists at the apical membrane which determine entry into the cell of Na⁺ -K⁺ APTase pump.

            It has been demonstrated that independent (although simultaneous) energy dependent carriers exist at the apical membrane which determine entry into the cell of Na⁺ by Na⁺ / H⁺ exchange and Cl^- by Cl^- / HCO₃^- exchange. The result is a “silent” or electrochemically neutral coupled entry mechanism. Absorption of the water by the gall bladder is a passive process and is linked to active solute transport. There is a direct correlation between water and electrolyte absorption with time. Evidence suggests that water transport occur as a result of local osmotic forces and is intimately related to the ultra structure of the cell.

 

 

 

 

 

 

 

            It is doubtful if the bile have any absorptive function under normal circumstances. It is well known, however, that when the common bile duct is obstructed, the bile is gradually absorbed and replaced by a colourless mucoid secretion.

 

(C)  GALL BLADDER SECRETION:

            Although the main function of the gall bladder is absorptive, gall bladder mucosa also secretes mucous substances variously called mucous, mucins, mucoprotiens, mucopolysaccharides and glycoproteins. About 20 ml of mucin is secreted in 24 hours. These substances constitute the ‘white bile’ found in the mucocele of the gall bladder where the cystic duct is blocked by a gall stone. The bile from the pathological gallbladders is more viscous than bile from normal gall bladders largely because of increase in these mucous substances.

            The bile ducts are provided with glands that secreted small quantities of mucus. This ‘White Bile’ is the secretion of mucous the mucous glands that continue to function even against a high backpressure. The discovery at the operation of ‘White Bile’ in the common duct in a patient suffering from obstructive jaundice indicates that complete obstruction has been present for many days and implies a poor prognosis ³¹.

 

(D)  GALL BLADDER AND BILIARY TRACT MOTOR ACTIVITY:

GALL BLADDER EMPTYING AND FILLING:

            Bile is stored in the biliary tract during the interdigestive periods and then delivered into the duodenum after meal stimulation. More recent information indicates that bile flow occurs probably in a continuous fashion, with some gall bladder emptying going on constantly. Nonetheless the ingestion of the food and the release of the Hormone cholecystokinin (CCK) constitute the major stimulus for gall bladder emptying. The factors responsible for the gall bladder filling and emptying include hormonal, neural, and mechanical factors. Alteration in the normal motor activity of the gall bladder and biliary tract disrupts the kinetics of the bile flow and the enterohepatic circulation of bile acids and has been linked to gall stone formation as well as heterogenous group of disorders known as biliary dyskinesia. Structure of terminal end of CBD is shown in figure 9.

 

 

 

 

 

 

REGULATION OF BILIARY SECRETION:

Gall bladder emptying and sphincter relaxation are under both

(a)    Humoral and

(b)   Neural influences.

These two interact to produce control.

(a)    HUMORAL EFFECT:

            Although CCK is believed to be the primary hormonal stimulus for gall bladder contraction, motilin, secretin, histamine, prostaglandins, Gastrin and glucagon have all been shown to have varying effects on the contractile process.

(i)      CHOLECYSTOKININ [CCK]:

            This hormone was the first extracted from the upper intestinal mucosa of the dogs by Ivy and Oldberg in 1928. It was isolated in pure from by Jorpes and Mutt (1962) and shown to be linear polypeptide containing 33 amino acids residues (Jorpes 1968); the activity of CCK residues is in the carboxyl-terminal position of the molecule. Jorpes and Mutt also showed that cholecystokinin (CCK) and pancreozymin (PZ) were one and the same substance.

            Protein and most other foodstuffs like acid, egg yolk and peptone serve as stimuli for CCK release from the duodenum, fat are the most potent factor including the release of CCK. Shortly after the release of CCK commences in response to a meal. Gall bladder concentration is initiated and serum level of CCK correlate with the degree of the gall bladder contraction and emptying. Maximal emptying (approximately 75 to 80 percent) occurs within 90-120 minutes after meal consumption. CCK receptor have been identified in the smooth muscles of the gall bladder, and the contractile process is probably mediated, at least in part, by changes in the relative concentration of intracellular cyclic nucleotides.

            Studies from Grossmann’s laboratory establishes that essential amino acids were more effective that essential amino acids were more effective than non essential amino acids, that only the l and not the d forms were effective and that tryptophan and phenylalanine were most effective in releasing CCK from the duodenal mucosa. Acid in the duodenum released only small amounts of CCK from the duodenal mucosa. Acid in the duodenum released only small amounts of CCK.

            Cholecytokinin has a potent stimulant action on the gall bladder muscle and an inhibitory action on the common duct sphincter are physiological processes and are likely to be directly involving no mediation by nerve although the possibility of H₂₊ receptor interaction has been raised.

 

(ii)SECRETIN:

            Bayliss discovered this hormone and Starling in 1902 was isolated in pure form by Jorpes and Mutt in 1961. It is a linear polypeptide containing 27 amino acid residues and is released from duodenal mucosa by acid. Secretin alone does not alter gall bladder pressure but potentates the action of CCK on the gall bladder and common duct sphincter, the latter role probably being physiological. In addition, secretin increases the flow of bile from the liver.

Role of Secretin in Controlling Bile Secretion.

            In addition to the strong stimulating effect of bile acids on bile secretion, the hormone secretin also increases bile secretion rate for several hours after a meal. However, this increases in secretion represents mainly secretion of a bicarbonate- rich watery solution by the epithelial cells of the bile ductules and ducts and not increased secretion of bile acids by liver parenchymal cells. The bicarbonate in turn passes into the small intestine and joins the bicarbonate from the pancreas in neutralising duodenal acid operates not only through its effects on the secretion by the liver ductules and duct as well.

 

(i)                  HISTAMINE:

            Histamine has been shown to cause marked increase in gall bladder pressure. Schoetz et al [1978] demonstrated the presence of inhibitory H₂ and stimulatory H₁ receptors in the primate gall bladder but their role is unclear.

 

(b)   NEURAL EFFECTS:

            The predominant neural factor regulating gall bladder motor activity is cholinergic (Parasympathetic) stimulation through the vagus nerves. Evidence for this relationship comes from a variety of studies, which demonstrates that direct and pharmacologic cholinergic stimulation is associated with release of acetylcholine and can be correlated with gall bladder contraction. Clinical experience suggests that truncal vagotomy reduces gall bladder emptying.

            The role of the sympathetic nervous system is unclear.

 

SPHINCTER OF ODDI AND BILIARY TRACT MOTOR ACTIVITY

            Kerilkamp and Boyden [1940] with the help of a special technique that involved maceration and preliminary dissection followed by hardening and final dissection showed that the sphincter of Oddi comprised of the following elements.

1.      SPHINCTER CHOLEDOCHUS

2.      SPHINCTER PANCREATICUS

3.      SPHINCTER AMPULLAE

 

1.      SPHINCTER CHOLEDOCHUS;

            It ensheathed the lower end of the common bile duct above its junction with the pancreatic duct. It is the only component that is always presents and is responsible for guarding the lower end of the common duct. Its function can be investigated by measuring the resistance offered to the passage of fluid in duodenum.

 

2.      SPHINCTER PANCREATICUS

            There is no information on the functional importance of the inconstant sphincter pancreaticus.

 

3.      SPHINCTER AMPULLAE:

            The mode of termination of the pancreatic and the common duct is variable; they may enter the duodenum independently, side by side or by common ampulla. When they terminate in ampulla, blockage of this outlet by a calculus or by spasm of its sphincter may allow bile to enter the pancreatic secretion to enter the bile duct.

            Ultimately, flow of bile into the duodenum is dependent on the co-ordination of gall bladder contraction and sphincter of Oddi relaxation. The sphincter and surrounding duodenal musculature appear to have phasic contractile activity that serves to propel the bile into the duodenum. During the interdigestive period, this activity, which may be regulated by the hormone Motilin, is sufficient to allow passage of some bile to pass into duodenum. This activity is probably modulated by a number of factors, including gut peptides, neural factors, enkaphalins. The bile duct itself has minimal, if any inherent motor activity and is believed to serve as a conduit for bile.

 

BILE FORMATION:

COMPOSITION OF BILE:

            Bile is a complex solution composed of water, organic lipids, and electrolytes, which is normally secreted by hepatocytes. The composition of bile is given in the table. The most abundant substance secreted in the bile is the bile salts, but also secreted or excreted in large concentrations and bilirubin cholesterol, lecithin, and the usual electrolytes of plasma. In the concentrating process in the gall bladder, water and large portions of the electrolytes (except calcium ions) are reabsorbed by the gall bladder mucosa, but essentially all other constituents, including especially the bile salts and the lipid substance cholesterol and lecithin are not reabsorbed and therefore become highly concentrated in the gall bladder bile.

            The electrolyte composition of bile is similar to that of extra-cellular fluid. Bile is isotonic and has a neutral or slightly alkaline pH. The protein content of bile is relatively low, although studies suggest that this may actually increase during gall stone formation. The predominant organic solutes present in bile are bile salts, cholesterol and phospholipids. Together these substances account for approximately 80 percent of the dry weight of bile.

 

BILE FORMATION AND SECRETION:

            Bile formation and secretion is a complex process that probably involves two distinct mechanisms. The active transport of bile acids by the hepatocytes into the bile canaliculi provides the osmotic gradient that causes the water to passively diffuse into the small ducts. This process has been referred to as “bile acid-dependent.” The second component involves the active transport of sodium and other solutes into the bile canaliculi with the passive diffusion and ultra filtration of water and small solutes. This “bile acid-independent” component accounts for a significant volume and has been shown, at least experimentally. To be identified by a number of pharmacological agents. A variety of other organic anions and cations are also transported in this manner. The role of canalicular microfibrils in this process is uncertain at this time. Once in the canaliculi, the, bile composition is further modified by secretin, a duodenally released peptide, and perhaps other peptides as well. Secretin increases bile secretion and is capable of stimulating secretion of an alkaline secretion from the ducts themselves.

 

FUNCTIONS OF BILE:

The functions of bile are as follows,

1.      Bilirubin and cholesterol are mainly excreted through this route.

2.      It neutralises the acidity of the gastric contents.

3.      Bile salts solubilize triglyceride fat.

4.      Bile salts help in the absorption of calcium, cholesterol and fat-soluble vitamins [A, D, E, & K] from the intestine.

5.      The products of the steroid hormones particularly sex hormones, thyroid and adrenal hormones are excreted in it.

6.      It is also the main route of excretion of some drugs and poisons such as salts of heavy metals, atropine strychnine and salicylates.

7.      Large molecules which cannot be excreted via this route.

 

BILE SALTS:

            The liver cells form about 0.5 gram of bile salts daily. The precursor of bile salt is cholesterol, which is either supplied in the diet or synthesised in the liver cells during the course of fat metabolism and then converted to cholic acid or chenodeoxycholic acid in about equal quantities. These acids then combine principally with glycine and to a lesser extent with taurine to form glyco- and tauro-conjugated bile acids. The salts of these acids are secreted in the bile.

 

FUNCTIONS OF BILE SALTS:

            Functions of the bile salts which are as follows,

(i)                  EMULSIFYING OR DETERGENT FUNCTION: They have a detergent action on the fat particles in the food, which decreases the surface tension of the particles and allows the agitation in the intestinal tract to break the fat globules into minute sizes.

(ii)                ABSORPTION OF FATTY ACIDS, MONOGLYCERIDES CHOLESTEROL AND OTHER LIPIDS FROM THE INTESTINAL TRACT: They do this by forming minute complexes with these lipids. The complexes are called micelles and they are highly soluble because of electrical charges of the bile salts.

(iii)               They absorb fat-soluble vitamins [A, D, E & K].

ENTERO-HEPATIC CIRCULATION OF BILE SALTS:

            The quantity of bile secreted by the liver each day is highly dependent on the availability of bile salts – the greater the quantity of bile salts in the entero-hepatic circulation (usually a total of about 2.5 grams), the greater the rate of bile secretion.

            The primary bile acids, chenodeoxycholic and cholic acid, are synthesised exclusively in the liver from cholesterol. After conjugation with either taurine or glycine, these substances are secreted into the extrahepatic biliary tract. During indigestive periods, the bulk of these bile acids are stored in the gall bladder. Bile salts and other solutes are concentrated in the gall bladder as described above and emptied in the duodenum in response to the meal stimulated release of CCK. Over 80 percent of the conjugated bile acids are relatively absorbed in the terminal ileum. The remaining portion is not absorbed undergoes bacteria mediated enzymatic deconjugation in the terminal ileum or colon, and then passively reabsorbed.  A small portion of unconjugated bile acids is not absorbed in this manner and undergoes enzymatic dehydroxylation by colonic bacteria and is converted to secondary bile acids, deoxycolic acid or lithocolic acid. A proportion of these secondary bile acids is then passively absorbed. Ultimately, all the bile acid moieties that are absorbed in the intestine are brought back through the portal circulation of the liver. As a result of this efficient entero-hepatic circulation, 95 percent of hepatic synthesised bile acid pool is available for re-circulation. This system allows a relatively small pool of bile acids to re-circulate six to twelve times per day with minimal loss during each pass. Only about 5 percent of bile is excreted in the faeces as acidic sterol. The hepatic synthesis of bile acids is regulated by entero-hepatic circulation through a negative feedback system.