Robert Alan Wood, M.D.

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0002049/robert-wood

Also blood pressure chart lower number perindopril 2 mg generic, administration of drugs that decrease tone of the sphincter has been successfully tried pulse pressure tamponade perindopril 2 mg buy low cost. Popularly heart attack meme perindopril 8 mg mastercard, it is known as "heartburn" as the patient describes the pain in the retrosternal area heart attack lyrics demi buy perindopril 4 mg overnight delivery. Aerophagia While eating and drinking hypertension 7th safe perindopril 4 mg, some volume of air is automati cally swallowed. A small volume of the swallowed air is removed by belching (regurgitation of air) and a volume of it enters into the intestine. Note, the body of esophagus is dilated (upper arrow) and lower part is narrowed giving appearance of a rat tail (lower arrow). These individuals develop abdominal discomfort and borborygmi (rumbling noises in the intestine and colon). Esophagus is a unique structure having both striated and smooth muscle, and both the muscle are innervated by vagus nerve. Esophageal peristalsis is initiated by swallowing, which may be air, or saliva, and need not be food. Special features of esophageal muscles, Esophageal sphincters, Types and mechanism of esophageal peristalsis, Causes and treatment of achalasia cardia and reflux esophagitis. Correlate the electrophysiology of gastric contractions with gastric motor dysfunctions. Functionally, stomach is divided into two parts: the proximal stomach (consisting mainly the body of the stomach), which acts as a reservoir, and the distal stomach (consist ing mainly the antrum of the stomach), which acts as a pump. The proximal stomach, for its property of receptive relaxation, receives and stores food, and for its tonic contractions pushes food toward the antrum. The distal stomach for its property of phasic contractions, mixes, grinds, and breaks down food into smaller particles and regulates emptying of food into small intestine through gastroduodenal junctions. To allow the stomach to act as a reservoir for storage of large amount of food of a single meal. To cut foodstuff into smaller particles and mix the food with gastric juice, the process in which food is converted into chyme. To allow gastric contents to enter the duodenum at a slow but controlled rate, so that duodenum and jeju num being narrower tubes, handle the chyme appro priately. He was the first scientist to systematically study the digestive processes in human beings. He was first physiologist to study gastric motility in a patient with a gastric fistula. Proximal Stomach the proximal part of stomach accommodates large volume of food (as large as 2 to 4 liters) without much increase in intragastric pressure. Chapter 48: Gastric Motility 405 Gastroduodenal Junction the junction between the stomach and duodenum is called gastroduodenal junction. There is a sphincter in the pylorus consisting of a ring like thickening of circular muscle fibers, known as pyloric sphincter. To allow gastric contents to enter the duodenum at a slow and controlled rate (the rate at which duodenum is capable of possessing the chyme). Therefore, food in fundus and body remains relatively unmixed for a longer duration. The antrum, physiologically acts as a mechanical pump, which propels food towards the pylorus and helps in grinding and mixing of food. Antral contractions break foodstuff into smaller par ticles and mix food thoroughly with gastric juice that help in partial digestion of food. Pyloric sphincter remains partially closed and does not allow easy entry of gastric contents into the duodenum. However, vigorous contractions of gastric antrum help gastric content enter the duodenum at a slow but controlled rate. After grinding and mixing of food with gastric juice, the gastric content is now called chyme. The duodenal mucosa is relatively resistant to bile acids but sensitive to gastric acid, whereas gastric mucosa is appar ently resistant to gastric acid but sensitive to bile acids. Therefore, in case of incompetent pyloric sphincter, regurgitation of duodenal content (containing bile acids) into the stomach usually results in gastric ulcer. On the other hand, rapid emptying of gastric contents (containing acidic chyme) into the duodenum promptly causes duodenal ulcer. Normally, as soon as acidic chyme from stomach enters the duodenum, the acidic pH stimulates release of secretin from S cells of duodenum and upper jejunum. Therefore, immediately the acidic chyme is neutralized by the aqueous component of pancreatic juice. However, when gastric emptying is faster or secretion of pancreatic juice is less, the possibility of duodenal ulcer is more. Moreover, the content in the part of the duodenum above the sphincter Oddi does not get well mixed with pancreatic secretion. Neural Control of Pyloric Part the pylorus is richly innervated by parasympathetic (vagal) and sympathetic fibers. However, activation of parasympathetic fibers have both stimulating and inhibiting effects. However, the circular muscle layer of the muscularis externa is more prominent than the longitudinal layer. In general, muscularis externa in fundus and body is thin and in antrum and pylorus is considerably thick. Note, muscularis externa is more developed in the antrum of the stomach (B) compared to the body of the stomach (A). Basic Histology, by V Subhadra Devi, 1st edition, 2016; Jaypee Brothers Medical Publishers (P) Ltd. Parasympathetic innervation (vagal fibers) stimulates whereas sympathetic innervation (fibers originate from celiac plexus) inhibits gastric motility and secretion. Axons arising from intramural plexuses innervate smooth muscles and secretory cells. Some of the sensory fibers act as afferent link between the sensory receptors of the gastric mucosa and the intramural plexuses. Few of these afferent fibers provide information about an intragastric pressure, gastric distention, chemical composition and pH of gastric content, and pain sensation originating in the stomach. The contractions that result from these action potentials are stronger than the contractions that occur in the absence of these action potentials. Acetylcholine and gastrin improve gastric contractility by enhancing the amplitude and duration of the plateau phase of gastric slow waves. Electrophysiology of Gastric Motility the peristaltic waves in the stomach occur usually at the frequency of gastric slow waves. These peristaltic waves are generated by a pacemaker zone located in the middle of the body of the stomach. The frequency of peristaltic wave is about 3 per minute in human being and the waves are conducted from body toward pylorus. The gastric slow wave has four phases that resem ble the action potentials of cardiac muscle. However, it does not overshoot and last for a longer period (10 times that of cardiac action potential). The smooth muscles of stomach contract when the depolarization of the slow wave exceeds the threshold for contraction. The force of contraction depends on the degree, frequency and duration of depolarization. Greater the depolarization and longer the muscle cells remain depolarized (above threshold), greater is the force of contraction. If stomach is allowed to remain empty for a longer duration, contractions become vigorous. The antral contractions are intense in such a situa tion and are associated with the relaxation of pyloric sphincter. Gastric Relaxations Receptive Relaxation this is the relaxation of the fundus and body of the stom ach in response to chewing and swallowing of food. Because of receptive relaxation, the intragastric pressure does not rise in spite of accumulation of a large volume of food. Normally, gastric motility induced by vagal stimulation is mediated by cholinergic fibers. Receptive relaxation is vagally mediated and adaptive relaxation is mainly a vagovagal reflex. Adaptive and Feedback Relaxations There are other two types of gastric relaxations: adaptive and feedback. The adaptive relaxation is the relaxation of stomach triggered by distension of stomach. Receptive relaxa tion starts even before food reaches stomach whereas adaptive relaxation occurs in response to stretching of stomach wall. The feedback relaxation of stomach is a reflexive relaxation that occurs due to presence of food in proximal segment of small intestine. Acidic chyme and fatty acid in intestine inhibit gastric motility by both hormonal and neural mechanisms that cause feed back relaxation of stomach. It helps in propelling food into the antrum and mixing of food with gastric juice. Therefore, food does not enter the duodenum, rather is recirculated in the stomach. Migrating Motor Complex During the interdigestive phase, antrum of the stomach remains silent for about 75­90 minutes, after which a burst of electrical and motor activities occurs. Peristalsis After about half an hour following gastric filling, gastric peristalsis starts. The pacemaker for gastric peristalsis is located in the middle of the stomach close toward greater cur vature. Reverse Peristalsis Sometimes in abnormal situations, peristalsis occurs in reverse direction, which starts in the lower parts of the body and proceeds toward esophagus. The lower and upper esophageal sphincters relax so that gastric content is forced out of esophagus and oral cavity. Note, pyloric sphincter is closed in step A, B, and C during which thorough mixing and grinding of food occurs and the food material is converted into chyme. In stage D, sphincter is partially opened that causes slow emptying of gastric content into duodenum. Usually, it occurs at a slow but controlled rate so that duodenum and jejunum comfortably accommodate and process the chyme at a desired rate. Retropulsion the terminal part of antrum exhibits rapid and forceful contractions that forces the chyme to be propelled back toward the proximal part of the antrum and body of the stomach. Retropulsion is very effective in mixing and grinding the larger food particles into smaller ones. Then, pyloric sphincter partially opens and gastric pump slowly pushes food into duodenum. Mechanism of Gastric Emptying When food enters stomach, stomach relaxes due to receptive and adaptive relaxations. Gastric empty ing occurs by three mechanisms: peristaltic contraction, antral contraction, and retropulsion. Physiological Significance As the muscle layers in the fundus and body are thin, contractions in these parts of the stomach are weak. Therefore, gastric content in body of stomach settles into different layers based on their density. Fat content of the food forms an oily layer on the top of the other gastric contents. This is why fat is emptied slower than the carbohydrate and protein (Applica tion Box 48. Liquid portion of the food flow around the mass and enter the antrum, and from there into the duodenum. Fat ensures slow gastric emptying and slow absorption of alcohol from intestine, and therefore the person drives his car back after the party, even after a heavy drink. Peristaltic Contractions the peristaltic contractions usually begin in the middle of the stomach and proceeds in a ring like fashion toward pylorus. The velocity and magnitude of contraction increase as the contractile waves approach pylorus. As contractions are weak in the fundus and body of the stomach, the proximal portion of stomach mainly serves the reservoir function. Therefore, usually proper mixing of food with gastric secretion does not occur in these parts of the stomach. Antral Contractions Antral contractions help thorough mixing of food with the gastric juice. But, as the pyloric sphinc ter remains closed, peristaltic wave fails to push food into the duodenum, rather food returns back into the body of the stomach. After few such contractions, pylorus opens partially with a narrow opening at the center. Regulation of Gastric Emptying Gastric emptying is regulated by both neural and hormonal mechanisms. The upper part of the small intestine (duode num and jejunum) contains receptors that detect change in pH, osmotic pressure, and products of fat and protein digestion. The chyme that enters duodenum is highly acidic and hypertonic and contains products of protein and fat digestion. Acid in the duodenum: With decrease in the pH of the duodenal content the rate of gastric emptying decreases. Products of fat digestion: Products of fat digestion like fatty acids and also some fat molecules in the duode nal content inhibit gastric emptying.

Mechanism and Regulation of Secretion Mechanism the exact mechanism of intestinal secretion is not clear: 1 blood pressure medication and adderall purchase perindopril line. The cations are secreted by active transport and anions are transported along with cations to maintain electroneutrality blood pressure under 100 purchase generic perindopril online. Mucin is the major component of mucous that forms a gel to cover the mucosal epithelium heart attack enrique lyrics discount perindopril 4 mg buy line. Mucous protects the intestinal epithelium and helps in smooth passage of chyme through the intestinal lumen blood pressure medication benicar perindopril 4 mg purchase fast delivery. Experiment to Study Intestinal Secretion In animal models blood pressure medication kalan cheap perindopril online, experiments are performed to study the rate and composition of intestinal secretion. In these animals, a loop of intestine is resected and both ends of the loop are connected to anterior abdominal wall in such a way that they open to outside. Thereafter, various stimuli are applied on the loop and their effects are studied. This provides suitable environment for digestion and absorption of food materials in the intestine. Mucus in the intestinal secretion contains immunoglobulins that play an important role in local defenses. These microorganisms are present mainly in the ileum than in upper part of the intestine. This is because the acidic content of duodenum and upper jejunum do not favor growth of bacteria: 1. Normally, bacteria are lost in the stool and replaced in the intestine by their natural growth. However, excess loss of bacterial flora in diseases like acute diarrhea results in improper digestion and absorption (Clinical Box 43. Bile salts are converted to bile acids by intestinal bacteria, which are then absorbed into portal blood from intestine and colon. This occurs due to production of amines like indole and skatole by intestinal bacteria. Therefore, poorly absorbable antibiotic like neomycin that modifies bacterial flora decreases plasma cholesterol. Though these bacteria are nonpathogenic and beneficial, their entry into systemic circulation can cause systemic sepsis as occurs in ionizing radiation that breaks the intestinal defense barrier. Bacterial flora is not well developed in infants and is slowly established during early childhood. Therefore, lactobacilli treatment is a must in any acute gastroenteritis in children. Applied Physiology Malabsorption Syndrome the commonest abnormality due to inappropriate intestinal secretion is malabsorption syndrome. However, malabsorption also occurs due to gastric, hepatic and pancreatic deficiencies. In malabsorption due to intestinal causes, the digestive and absorptive functions of small intestine are impaired. Therefore, unless the disease process significantly affects the adequate length of intestine, malabsorption does not develop. Similarly, only in surgical procedure that removes or bypasses more than 50% of the intestine, significant malabsorption occurs. In these conditions, hypoproteinemia develops early due to deficient absorption of amino acids. Functions of Intestinal Flora Intestinal bacteria are essential for many gut functions: 1. Normal bacterial flora is essential for digestion and absorption of essential nutrients including vitamins, minerals, and water. They produce chemicals that help in formation of short chain fatty acids, which help in growth of the intestinal mucosa. Fat soluble vitamins (A, D, E, and K) are also not properly absorbed due to defective fat absorption. Excretion of large amount of fat (steatorrhea) results in bulky, pale and foul-smelling stool. This condition is commonly observed in patients with surgically created blind loops of small intestine, which is popularly known as blind loop syndrome. Steatorrhea occurs due to excessive hydrolysis of conjugated bile salts by the bacteria. Intestinal secretion is very useful for digestion and absorption of nutrients from intestine, as it contain enzymes for digestion of all types of nutrients. Therefore, nature has given a vast surface area for absorption by providing microvilli and brush borders. Intestinal bacteria facilitate the process of digestion and absorption and help in synthesis of few vitamins. Diarrhea occurs, if the secretion of water is increased or absorption of water is decreased. Intestinal glands, Intestinal mucosa, Intestinal endocrine cells, Mechanism and regulation of intestinal secretion, Composition and functions of intestinal secretion, Bacterial flora of intestine, may come as Short Questions. Layers of wall of intestine, Arrangement of villi and microvilli in the mucosa, Structure of intestinal glands, Structure of intestinal mucosa, Intestinal endocrine cells and their secretions, Composition and functions of intestinal secretion, Mechanism and regulation of intestinal secretion, Experiment to study intestinal secretion, What is Thiry-Vella loop, Types of bacteria in bacterial flora of intestine, Functions of bacterial flora, Causes of malabsorption syndrome, Blind loop syndrome. The secretion of large intestine is not considered so important physiologically as it does not help in digestion. The major function of large intestine is the absorption of water and electrolytes. It absorbs about 90% of its load (mainly water is absorbed) in the form of chyme presented to it from the ileum. Of about 2 liters of isotonic chyme that enters large intestine, only about 200 ml is excreted as feces. Lamina propria contains intestinal glands and submucosa contains lymphatic nodules. Colonic Secretion Composition of Secretion Secretion of large intestine contains mainly mucous ­ secreted by goblet cells. Length of colon (ascending, transverse, descending and sigmoid colon) in adult is about 110 cm. The diameter of large intestine is bigger than small intestine, which favours slow passage of chyme through it and also absorption of maximum quantity of water during its passage. There are no villi, though the mucosal epithelium is folded to give villi like appearance to some extent. There are many crypts of Lieberkühn in the mucous membrane that secrete a solution isotonic to that of plasma. Mechanism of Secretion There are crypts in the mucous membrane that secrete a solution isotonic to that of plasma. Mucous secreted from goblet cells has following functions: - Protects intestinal mucosa - Help in stool formation - Lubricate the intestinal mass - Neutralize the acid which is formed by bacteria in the large intestine. About 90% water is reabsorbed from the intestinal contents: - Therefore, when content of large intestine passes very slowly or there is stagnation, constipation occurs due to absorption of more water that causes solidification of stool. Transfer of electrolytes and water: Large intestine can absorb Na+, K+, Cl-, glucose and certain vitamins. Na+ is actively absorbed from the colon and water follows along the osmotic gradient generated by absorption of Na+ and Cl-. Functions of Colonic Bacteria the physiological role of colonic bacterial flora are: 1. Acidic reaction of stool: Organic acids formed from carbohydrates by bacteria causes slightly acidic reaction of the stool (pH 5 to 7): a. Production of amines: A number of amines are formed in the colon by bacterial enzymes that decarboxylate amino acids. These amines are histamine and tyramine which may be harmful if produced in excess quantity. Colour of stool: Pigments biliverdin and stercobilinogen formed from the bile pigments by the intestinal bacteria are responsible for the brown colour of the stool. In some individuals, more gas is produced in the intestine that causes cramps, borborygmi (rumbling noise) and abdominal discomfort. They produce about 8 liter of gas per day that contributes to flatus and colonic motility. Hence, in severe liver disease, hepatic encephalopathy (suppression of brain activities) occurs. Organisms At birth, the colon is sterile but the colonic bacterial flora becomes established early in life. The micro-organisms habituating the colon are bacilli such as mainly Escherchia coli and Enterobacter aerogens. Chapter 44: Secretion of Large Intestine 391 Absorption of Water Normally, about 1. As most of the nutrients are absorbed mainly in the duodenum and jejunum, the osmolality of intestinal content which is about 600 mOsm/kg H2O, decreases to about 200 mOsm/kg H2O in the ileum and colon. Role of rectum in defecation reflex is discussed in `Motility of Large Intestine". Though, normally absorption of water from rectum is not significant, the absorptive capacity is more (Clinical Box 44. Drugs that are administered rectally include purgatives, sedatives, anesthetics, and tranquilizers. However, care should be taken to control the volume of enema introduced into rectum in children as excess water absorption can cause water intoxication. Colonic bacteria are involved in gas production that facilitates the process of bowel movement by distending the bowel and also they help in synthesis of few vitamins. Colonic bacterial flora, Colonic secretion, Role of colon in water and electrolyte absorption, Absorption of water by intestine, may come as Short Questions. Layers of wall of large intestine, Structure of large intestinal glands, Structure of large intestinal mucosa, Mechanism and regulation of colonic secretion, Types of bacteria in bacterial flora of intestine, Functions of bacterial flora in large intestine, How is water secreted and absorbed in different parts of the colon. Electromechanical Coupling Like skeletal muscle, smooth muscle have electromechanical coupling. That means, depolarization of the membrane causes opening of voltage-gated Ca++ channels and increases cytosolic calcium, which leads to muscle contraction. Pharmacomechanical Coupling In addition, smooth muscles have an additional mechanism of pharmacomechanical coupling, in which binding of a ligand to its receptor on the muscle membrane leads to opening of Ca++ channels and increase in cytosolic calcium without change in membrane potential. Mechanomechanical Coupling Stretch of smooth muscle causes muscle contraction, which is known as mechanomechanical coupling. Stretch on muscle opens stretch-sensitive calcium channel on the muscle cell membrane. When action potentials are associated with slow waves, they occur on the plateau phase (phase 2). The electrical slow waves are wide spontaneous rhythmic fluctuations in the membrane potential ranging between ­65 and ­40 mV. Slow waves are generated by the interstitial cells of Cajal located between the longitudinal and circular muscle layers. Interstitial cells have long processes that form gap junctions with longitudinal and circular muscle cells. This enables easy and rapid conduction of slow waves from the interstitial cells into the smooth muscles. Note that frequency is least in stomach (3/min) and maximum in intestine (15/min). Phase 1: this is the rising phase (depolarization), which occurs due to opening of voltage gated Ca++ channel. Phase 2: this is the plateau phase that occurs due to balance between inward Ca++ current and outward K+ current. Phase 3: this is the falling phase (repolarization) occurring due to activation of voltage gated K+ channel. Frequency: the frequency of slow waves is 3/min in stomach, 6 to 10/min in colon, 15/min in jejunum and ileum, and 18/min in duodenum. Action Potentials When the peak of a slow wave exceeds the threshold, action potential is triggered from the peak. Note, once the threshold is reached, action potential is generated on the peak of slow wave. Note that with increased number of action potential on a slow wave increases the magnitude of contraction and contraction does not occur in the absence of action potential. The magnitude and frequency of action potential are enhanced by vagal stimulation and inhibited by sympathetic stimulation. Relationship between electrical and mechanical responses: Slow waves that are not accompanied by action potentials do not elicit contraction, whereas, slow waves that are accompanied by action potentials evoke contraction. The greater the frequency of action potential (that occur at the peak of slow waves), the more intense is the contraction. However, the electrical coupling between circular cells is better than the longitudinal cells because the circular cells have more gap junctions. They neither form regular neuromuscular junctions nor do they release neurotransmitters at their axon terminal. Rather, most of motor axons release transmitters from varicosities that occur all along their axon, during propagation of an action potential, and the neurotransmitter diffuses to reach the muscle or interstitial cells (refer to . Cell bodies of excitatory motor neurons are present in the myenteric plexus and the axons project aborally to innervate muscle fibers. Stimulation of secretomotor neurons release histamine during allergic reactions and produce neurogenic secretory diarrhea during stress. Propulsion of food is achieved by peristaltic movement; trituration and mixing are accomplished by retropulsive and segmental movements. These neurons stimulate circular muscle contraction, and help in formation and progression of contractile ring behind the stimulus. These neurons assist in ensuing relaxation of circular muscle in the portion of the gut ahead of the stimulus.

Types of Blood Flow Blood flow is of two types: laminar (streamline) flow and turbulent flow blood pressure medication leg cramps buy 2 mg perindopril. The layer of the blood blood pressure quizlet purchase perindopril 2 mg amex, which is in close contact with the wall of the vessel heart attack xoxo buy genuine perindopril online, does not move at all due to the frictional resistance with the vessel wall pulse pressure 40 order perindopril cheap online, the next layer moves with lesser velocity hypertension 30 year old male buy perindopril 2 mg low price. However, laminar flow occurs up to a certain velocity beyond which the flow becomes turbulent. In cardiovascular system, at the site of constriction, increase in the velocity of blood flow makes the flow turbulent. Therefore, a murmurish sound is heard on auscultation at the site of constriction of the vessel or cardiac orifice. For example, a bruit is auscultated over an arterial constriction, or a murmur is heard over a stenotic cardiac valve. Poiseuille-Hagen Formula Poiseuille-Hagen formula denotes the relationship between viscosity of the fluid with the radius and length of the tube. F = (Pa ­ Pv) × /8 × 1/h × r4/L Where, F = Flow Pa ­ Pv = Pressure difference between the both ends of the tube h= Viscosity of fluid r = Radius of tube L = Length of tube As discussed above, flow is equal to the pressure difference divided by resistance. Therefore, resistance (R) is calculated from the following formula: 8 L R= r 4 Flow varies directly with the fourth power of the radius. Blood flow is markedly affected by a small change in the diameter of the blood vessel. The flow becomes double in a vessel by just increasing the radius to about 20% Consequently, blood flow is significantly altered by mildly changing the diameter of vessels. In fact, blood pressure is markedly increased by vasoconstriction Turbulent Flow the turbulent flow occurs when velocity is above critical velocity. Turbulence of flow depends on the diameter of the vessel and the viscosity of the blood. On the contrary, resistance is inversely proportional to the radius (discussed below). Factors Affecting Peripheral Resistance Peripheral resistance is determined by two main factors: Caliber of blood vessel and viscosity of blood. Radius of Blood Vessel the radius of the blood vessel significantly affects peripheral resistance. Decrease in radius of vessels to half increases peripheral resistance by 16 times. Conversely, when radius is doubled, resistance is reduced to 6% of its previous value. Therefore, the smaller branch that receives peripheral blood from the main artery contains less number of cells, which is called as plasma skimming. Temperature Increase in body temperature decreases viscosity and decrease in temperature increases viscosity. Plasma Skimming In blood vessels, cells mostly accumulate at the center of the flowing column of blood. Therefore, the portion of blood, which is available at the periphery of blood vessel (close to the vessel wall) has low cell content. Blood entering into smaller branches arising from a large vessel mainly comes from the peripheral part of the column of the blood. This explains why the hematocrit of capillary blood is about 25% less than the whole-body hematocrit. Viscosity mainly depends on the factors like hematocrit, composition of plasma, resistance of red cells to deformation and temperature. Hematocrit Hematocrit is the single most factor that greatly affects viscosity of blood. Hematocrit is the packed cell volume, which depends mainly on the number of red cells in the blood. The effect of change in viscosity on resistance is less in smaller vessels than in the larger vessels. Critical Closing Pressure In a rigid tube, a linear relationship exists between flow and pressure. Especially in capillaries, flow ceases when pressure is reduced beyond a point (but pressure is not zero). This is explained by two factors: (i) some pressure is required to force the red cells to pass through the capillaries which have the smaller diameter than the red cells, and (ii) blood vessels are surrounded by tissues that exert pressure (tissue pressure) on them. Thus, intraluminal pressure in capillaries should be more than the tissue pressure for flow to resume. Composition of Plasma In plasma, it is mainly the concentration of plasma proteins that affects viscosity. Viscosity increases in conditions in which concentration of plasma protein is more, for example, in paraproteinemia and multiple myeloma (increase in myeloma protein). Resistance of Red Cells to Deformation When the red cells become rigid as seen in hereditary spherocytosis, viscosity increases. In a blood vessel, the flow is absent below certain pressure, called as critical closing pressure. The other radius is infinite, so, T P= or T = P × r r So, in a small diameter blood vessel, less wall tension is required to balance the distending pressure. The relationship between intraluminal extending pressure (P) and the tension (T) developed in the wall of a hollow structure. Note, in a spherical structure, the tension in the wall is the product of intraspherical pressure and the radius (r) of the sphere. If the thickness of the vessel wall (w) is taken into consideration, like in an artery, r Wall tension (T) = P × w Application of Laplace Law the Laplace law helps us to understand the physiological mechanisms in altered situations and pathological conditions affecting the functioning of many organs. In hollow viscus like bladder, ventricle or the alveoli of the lungs, the wall tension depends on the distending pressure and its radius. That means the wall tension increases when the organ gets filled (distending pressure rises) or the cavity size (radius) increases. Also the wall tension decreases when the wall thickness is more and the wall tension increases when the wall thickness decreases. On the other hand, in a dilated heart as seen in heart failure, more energy is required to pump blood as the wall tension is more. Therefore, a dilated or distended heart pumps blood less efficiently (Clinical Box 92. At the area of constriction, lateral pressure decreases and therefore perfusion decreases. Plasma skimming, Critical closing pressure, Relationship between dynamic and lateral pressure in vascular system, Laminar and turbulent flow, Application of Laplace law, are asked as Short Questions in exam. What is laminar flow, What is turbulent flow, What is critical velocity, What are the differences between laminar flow and turbulent flow, What is Reynolds number, What is Poiseuille-Hagen formula, What is vascular hindrance, What is hematological hindrance, List the factors and their contribution to hematological hindrance, Why acute myocardial infarction is common in aortic stenosis, What is plasma skimming, What is critical closing pressure, What is the law of Laplace, Why are capillaries less prone to rupture, Why does the dilated heart fail faster. Understand the importance of sympathetic innervation of arterial system for maintaining arterial volume and pressure. Describe the principle of arterial hemodynamics in in various physiological conditions. These vessels have all the three layers, namely tunica intima, tunica media and tunica adventitia. The tunica media containing smooth muscle is thicker in the arterial compartment than the other compartments of circulatory system. However, the amount of smooth mus cle present varies in different parts of arterial system (for details, refer to . In these ves sels, the quantity of elastic component is more than the muscle component. Increase in vasoconstrictor tone increa ses and decrease in vasoconstrictor tone decreases blood pressure. In fact, a significant fall in blood pressure occurs when blood passes through arterioles. During systole, forward movement of blood is due to the energy created by forceful ejection of blood that occurs due to ventricular contraction. Had the aorta and large arteries been stiff (no recoil ing effect), flow of blood during diastole would have stopped and that would have resulted in intermittent blood flow only during systole. Thus, blood moves continuously during systole and diastole due to the Windkessel effect of elastic arteries. A Arterial Pressure Pulse Arterial pressure pulse is the pressure wave that travels along the wall of the arteries created by forceful ejection of blood into the arterial system during ventricular systole. These pressure waves are felt as arterial pulses when clini cally examined by the physician. The velocity of transmission of pulse wave in the wall of the artery is fifteen times the velocity of flow of blood in the lumen of the artery. The amplitude and the pattern of arterial pulse also change from central arteries to peripheral arteries. The central arterial pulse has higher amplitude, steep ascending limb, less sharp peak and incissura in the upper part of the descending limb, which is less steep. The peripheral arterial pulse has steep ascending limb, sharp peak, steep descending limbs, and the dicrotic notch (instead of incissura) present toward the lower part in the descending limb. The percussion wave or tidal wave occurs due to ejection of blood dur ing ventricular systole. The dicrotic wave occurs due to rebound of blood against the closed aortic valve during diastole. The aorta and the large arteries due to their elastic recoil property, maintain forward movement of blood during diastole (details, described below). Small arteries, arterioles and metarterioles are richly innervated by sympathetic fibers and offer maximum resistance to blood flow. Functional Aspects Arterial Elasticity Aorta and large arteries have more compliance due to the presence of more elastic elements in their wall. When blood is ejected forcefully into the aorta and its major branches during ventricular systole, these vessels are dis tended. During diastole, the aortic wall immediately recoils back to its previous position. Due to the Windkessel effect, the vessel wall that recoils back on the blood column pushes the blood to move in forward direction during diastole. Arterial Pressure Arterial pressure is defined as the lateral pressure exerted by the column of blood on the walls of the arteries. The pressure in the arteries fluctuates during systole and diastole of the cardiac cycle. The maximum pressure is recorded during systole (systolic blood pressure) and the minimum pressure is recorded during diastole (diastolic blood pressure). In adults, the systolic pressure ranges between 100­ 140 mm of Hg and diastolic pressure ranges between 60­90 mm Hg (for details of blood pressure, refer Chapter 96). Indirect Methods Blood pressure is usually measured with the help of a sphygmomanometer. In this method, the cuff of the sphygmomanometer is wrapped around the arm of the subject. The cuff is then inflated until the air pressure in the cuff over comes the arterial pressure and obliterates the arterial lumen. This is confirmed by palpating the radial pulse that disappears when the cuff pressure is raised above the arterial pressure. When pressure in the cuff reaches just below the arte rial pressure, blood escapes beyond the occlusion into the peripheral part of the artery and pulse starts reap pearing. This is detected by the appearance of sounds in the stethoscope, which is taken as the systolic pressure. The blood pressure can be measured by three methods: (1) palpatory, (2) auscultatory, and (3) oscillatory method. Ideally, blood pressure should be measured first by the palpatory and then by the auscultatory method. The change in pressure during systole and diastole of a cardiac cycle produces pulse pressure. It grossly decreases across the arterioles, almost negligible in capillaries and nil in veins. Direct Methods the blood pressure is measured directly by placing a can nula in the artery and connecting the cannula to a mercury manometer or a pressure transducer. Palpatory Method In palpatory method, pressure in the cuff is progressively raised and radial artery pulse is palpated simultaneously. Phase I: Sudden appearance of faint tapping sound which becomes gradually louder and clea rer during the succeeding 10 mm Hg fall in pressure. Appearance of the sound is recorded as systolic blood pressure and disappearance of sound is recorded as dias tolic blood pressure. In persons having severe hyperten sion, muffling rather than the disappearance of sound is taken as diastolic pressure. Note, diaph ragm of stethoscope is placed on brachial artery for auscultating sounds. Oscillatory Method In oscillatory method, the procedure is same as that of palpatory method. The pressure in the cuff is raised and the appearance and the disappearance of the oscillations of the mercury column are noted. The point of appearance of the oscillation gives systolic pressure and the point of disappearance of the oscillations gives diastolic pressure. Auscultatory Method In auscultatory method, pressure in the cuff is raised by about 20 mm Hg above palpatory level and then progres sively lowered during which brachial artery is auscultated for sounds by placing the diaphragm of a stethoscope on it. The Windkessel effect is due to arterial elasticity, which facilitates the movement of blood in arteries in forward direction during diastole. The more quantity of smooth muscle in comparison to the vessel wall in arterioles and metarterioles offers resistance to distension.

Thus blood pressure solution scam buy perindopril 8 mg cheap, cortisol excess causes maldistribution of fat in the body that result in truncal obesity pulse pressure method generic perindopril 2 mg buy online, moon face and buffalo hump with thinning of extremities arrhythmia 10 cheap perindopril 2 mg line. The exact cause of peculiar distribution of fat is not known blood pressure 80 over 50 discount 8 mg perindopril otc, but it is associated with insulin resistance and/or increase in insulin level blood pressure chart record keeping generic 8 mg perindopril visa. Therefore, obesity is restricted by the negative feedback actions of leptin (leptin inhibits feeding). To summarize the effect of cortisol on metabolisms, it is an important diabetogenic, ketogenic, and anti-insulin hormone (Flowchart 59. Probably, this action is mediated by inhibition of Na+-Ca++ exchanger in the cell membrane so that the Ca++ concentration is maintained in the blood vessel smooth muscle cells. In adrenal insufficiency, blood vessels become unresponsive to catecholamines (Clinical Box 59. However, it is desirable to inject cortisol along with catecholamines as it maintains vascular reactivity. Also, cortisol mediates responsiveness of catecholamines to vasoconstrictors by its permissive action. Catecholamine injection without administration of cortisol in shock does not ensure adequate vasoconstriction and blood pressure continues to remains low. Permissive Actions of Cortisol Glucocorticoid is essential (even in small quantity) for some physiological actions of other hormones to take place. This is called permissive action of cortisol (as cortisol allows the specific actions of these hormones to occur, though it does not produce these effects by itself). Surfactant synthesis in the fetal lung and maturation of lungs during intrauterine life. It decreases the responsiveness to gustatory, olfactory, auditory, and visual stimuli. The patients with adrenal insufficiency develop changes in personality, and remain irritable and apprehensive. Steroid Cortisol Corticosterone Aldosterone Deoxycorticosterone Cortisone Mineralocorticoid activity 1 15 3000 100 0. The inotropic effect on skeletal muscle is due to increase in acetylcholine synthesis at the muscle-nerve terminals. However, cortisol in excess decreases muscle protein synthesis and promotes proteolysis. Therefore, in the absence of cortisol, free water clearance is impaired and dilution of urine is limited (Clinical Box 59. It also increases phosphate excretion by inhibiting reabsorption of it in proximal tubule. Sudden infusion of large volume of saline or glucose solution in such patient may result in water intoxication. Following infusion of glucose saline, the glucose is metabolized, but the body can not remove water as cortisol is lacking. The cells in the brain swell, that impairs the hypothalamic thermoregulatory centers. It decreases the synthesis of type-I collagen, which is a fundamental component of bone matrix. Thus, it decreases supply of Ca++ to the bones, which is essential for bone mineralization. Therefore, prolonged administration of cortisol may cause osteoporosis (Clinical Box 59. The patient develops clinical features of hyperaldosteronism, though the plasma aldosterone and plasma renin activity remains low. It may occur due to congenital deficiency of the hormone or ingestion of licorice. It is essential for the rapid clearance of a water Chapter 59: Adrenal Cortex 517 3. The intestinal enzyme system of fetal pattern to the postnatal or adult pattern is altered by cortisol, which is essential for disaccharides to be digested by the infants. All these actions allow the fetal lung to satisfactorily expand at the first breath. Effects on Blood Cells Though, cortisol influences all the three formed elements of blood, the impact is more on leucocytes. Though it causes mild neutrophilia and monocytosis, it causes profound lymphocytopenia, eosinopenia and basopenia. Cortisol decreases circulating lymphocyte count by decreasing mitotic activity of lymphocyte precursors. It decreases the ability of lymphocytes and monocytes to secrete cytokines that are essential for proliferation of lymphocytes. Cortisol causes eosinopenia by stimulating apoptosis (programmed cell death) of eosinophil. It facilitates sequestration of eosinophil in spleen and lungs (thus, decreases the peripheral eosinophil count). Effects on Inflammation Cortisol has profound anti-inflammatory and anti-allergic actions. The inflammatory responses include: dilation of capillaries, increased capillary permeability, migration of granulocytes to the site of injury and killing of the organisms or the insulting agents by the granulocytes, mainly neutrophils (for details, refer Chapter 19). It stimulates synthesis of lipocortins (a family of phosphoproteins) in the target cells. Lipocortin inhibits the activity of phospholipase A2; therefore, decreases the release of arachidonic acid, which is the precursor for many mediators of inflammation like prostaglandins, thromboxanes, leukotrienes, etc. Therefore, it decreases release of proteolytic enzymes and hyaluronidase from lysosomes that are required for inflammatory reactions to occur. Consequently, it decreases the release of histamine, an important mediator of inflammation (histamine causes vasodilation and increases capillary permeability). It prevents the margination of leucocytes and adherence of leucocytes to the capillary endothelial wall. Cortisol inhibits the expression of receptors in the endothelial cells that normally causes chemotactic peptides to interact with leucocytes to stick to the vessel endothelium. Though cortisol causes mild neutrophillia, it actually decreases the activity of leucocytes. Thus, it decreases the synthesis and deposition of fibrils at the site of inflammation. This is suggested to be the primary mechanism of antiinflammatory actions of cortisol (Flowchart 59. Nevertheless, the physician has to be cautious for use of cortisol to prevent inflammation (Clinical Box 59. However, it should not be prescribed for treating acute inflammations due to infections. If cortisol is given in infections, the toxic features of infection dramatically disappear due to its anti-inflammatory actions. But, actually infection spreads as cortisol suppresses immunity (discussed below). Thus, cortisol in such conditions masks the actual disease and delays the diagnosis. Therefore, cortisol should not be prescribed in acute infections like pneumonia, cholecystitis, pancreatitis, active tuberculosis etc. If situation warrants cortisol treatment in such conditions, it should always be prescribed with appropriate and adequate antibiotics. Cortisol inhibits degranulation of mast cells and, therefore, prevents release of histamine. Therefore, cortisol is used frequently for the treatment of allergy both locally and systemically (Clinical Box 59. The activated T cells kill organisms, secrete interleukins and activate type 1 helper-T cells that mediate immunological responses. Cortisol decreases circulating lymphocytes by inhibiting lymphocyte mitotic activity. It mainly decreases T cell population, especially type-I helper T cells by stimulating their apoptosis. Immature T cells in thymus and immature B and T cells in lymph nodes are destroyed by high level of plasma cortisol, which in turn decreases the size of thymus and lymph nodes. Cortisol inhibits the cytotoxic effects of T cells by inhibiting the transport of lymphocytes to the site of antigenic stimulation and by decreasing the production of cytokines from them. Allergy occurs due to antigen-antibody reaction that stimulates the release of histamine from mast cells. In local allergy, release of histamine locally causes redness, itching and swelling. In systemic allergy (anaphylaxis), histamine released into circulation inhibits heart that decreases cardiac output, and causes vasodilation that decreases blood pressure. The antiallergy effects of cortisol include the following: Chapter 59: Adrenal Cortex Flowchart 59. Important Note Indications and contraindications of cortisol use: Cortisol is used in the treatment of many diseases and also contraindicated for other diseases. Cortisol is used for the treatment of inflammatory diseases like rheumatoid arthritis, etc. When an inflammatory process is lifethreatening, administration of cortisol provides immediate relief. Cortisol is frequently used for prevention of transplant rejection as it inhibits cellular immunity. However, cortisol given for a long time decreases body immunity and, therefore, increases the susceptibility to various bacterial fungal and viral infections. For example, in the management of bronchial asthma, to ensure effective bronchodilation, inhalation of both cortisol and sulbutamol is advised. Therefore, it is used in the treatment of keloid (the tumor of scar tissue) by local injections. A person suffering from acute infection should not be treated with steroids without antibiotics, though it suppresses inflammation and dramatically improves the condition. This is because cortisol suppresses immunity and spreads infection (person may die due to severe infection). Cortisol does not facilitate degradation of antibodies nor does it interfere in the interaction of antigen and antibodies. The decreased production of interleukin-1 by cortisol suppresses the febrile responses to inflammation. Prednisolone: It has predominantly glucocorticoid activity and less mineralocorticoid activity. Therefore, cortisol is prescribed cautiously in patients already having history of peptic ulcer. Thus, cortisol has profound inhibitory effects on cellular immunity, for which it is frequently used for prevention of transplant rejection. However, in large doses, it also suppresses production of antibodies and, therefore, 520 Section 6: Endocrine Physiology due to their direct action on the membrane channels or enzymes. He had pioneered in the study of functions hypothalamus, pituitary and the hypothalamo-pituitary-adrenocortical axis. Source: Papers relating to pituitary body, hypothalamus and parasympathetic nervous system. Role in Stress the most important function of cortisol is to protect the body against stress. In absence of glucocorticoids, body can not cope with stress even in mild intensity. Centripetal obesity and overweight: this is due to peculiar distribution of body fat in which fat is deposited more in the abdomen and upper back. Fat pad in lower neck and interscapular region gives the typical appearance of buffalo hump. Rapid Actions of Steroid As steroids act though transcription of genes in the cells, it takes hours to days for their full actions to manifest. However, recently, it has been observed that some of the steroid actions occur within few minutes. Note the presence of centripetal obesity, moon face, buffalo hump, pendulous abdomen with stria over it, poor muscle development and thin limbs, easy bruisability, poor wound healing (infections). Hypertension: Patient develops hypertension due to water accumulation as glucocorticoid in excess has significant mineralocorticoid activity. Increased angiotensinogen secretion by cortisol and direct action of cortisol on blood vessel contribute to it. Excess fat deposition in abdomen causes rapid stretching of the skin that results in formation of striae. Ecchymoses: the skin and subcutaneous tissue are thin as a result of protein catabolism. Therefore, minor injury causes ecchymoses and bruises (subcutaneous and intracutaneous hemorrhages). Proximal myopathy: the legs become thin due to proteolysis in the skeletal muscle and reduced bone mass. Poor wound healing: Hyperglycemia promotes growth of the organism at the wound site. Many patients develop hyperglycemia and glucose intolerance, and about 20% of patients develop insulin resistant diabetes mellitus. Osteoporosis develops due to decreased bone mineralization and decreased bone mass. However, tubercular infection of the adrenal gland, secondary metastasis, amyloidosis and cytomegalovirus infection affecting the gland may destroy and produce the disease.

For details of red cell destruction and bilirubin metabolism heart attack and vine cover purchase perindopril with amex, refer to Chapter 13 enrique heart attack purchase perindopril. Globin is the protein component hypertension medicines order 4 mg perindopril with mastercard, which is degraded into amino acids that enter the amino acid pool of the body and are reutilized whenever required blood pressure chart age 13 perindopril 2 mg purchase free shipping. Heme is catabolized by the microsomal oxygenase system to release iron blood pressure medication options buy perindopril canada, which joins the iron pool of the body. Chapter 41: Physiology of Liver, Liver Function Tests and Pathophysiology of Jaundice Table 41. Affinity to brain tissue Unconjugated bilirubin More Absent Present High Conjugated bilirubin Less (< 0. Normal Plasma Bilirubin Level: the normal concentration of bilirubin in plasma is 0. Types of Jaundice Clinically, jaundice is detected when bilirubin level is more than 2 mg/dL. Physiologically, the causes of jaundice are divided broadly into two categories: increased production of bilirubin and decreased excretion of bilirubin. Decreased Excretion of Bilirubin the excretion of bilirubin is impaired when liver cannot conjugate bilirubin efficiently, which is called hepatic jaundice, or when conjugated bilirubin cannot be excreted in bile due to biliary obstruction, which is called obstructive jaundice. Hepatic jaundice commonly occurs in viral hepatitis and obstructive jaundice is commonly seen in gallstones (stone in the common bile duct) or stricture of bile duct. However, hepatic and obstructive jaundice overlap in their pathophysiologic processes. Increased Production of Bilirubin Production of bilirubin is increased in hemolysis. Hemolytic Bilirubinemia Fecal stercobilinogen Urinary urobilinogen Urinary bilirubin van den Bergh test Liver function Mild Increased Increased Absent Indirect Normal Hepatic Moderate Decreased Decreased Present Biphasic Impaired Obstructive Severe Absent Absent Present Direct May be impaired 2. Consequently, conjugated bilirubin (bilirubin glucuronide) is excreted in the urine. Plasma albumin may be low as diseased liver cannot synthesize the normal amount of albumin. Plasma globulins are high in liver disease because of a rise in the gamma-globulin fraction. Neonatal jaundice could be due to defective conjugation of bilirubin (Clinical Box 41. In hepatic jaundice, narrowing of biliary canaliculi occurs very often resulting in intrahepatic obstruction (stasis). In obstructive jaundice, biliary stasis behind the site of obstruction causes damage to the hepatocytes. Obstructive Jaundice Obstructive jaundice occurs due to obstruction to bile secretion into intestine. As bile salt is reduced in intestine, there is an increased fecal excretion of fat (steatorrhea). The conjugated bilirubin accumulates proximal to the obstruction, and is regurgitated by the liver cells into the bloodstream. Therefore, the level of conjugated bilirubin in the blood is high, which is excreted in urine and causes deep yellow urine. Like conjugated bilirubin, bile salts are also regurgitated into the blood stream, and excreted in urine. But, later, prolonged biliary stasis damages the liver and impairs liver functions. The test is based on the principle that excess of water soluble bilirubinglucuronide gives a reddish-violet color when brought in contact with diazo reagent. If the color appears late, or only after addition of alcohol, the test is said to be indirect positive. The jaundice usually appears on the second or third day of life and disappears within a week. It occurs due to subnormal activity of glucuronyl transferase that impairs conjugation of bilirubin in hepatocyte. Laboratory Diagnosis of Jaundice Hemolytic Jaundice In hemolytic jaundice, excessive production of bilirubin allows liver to conjugate more than the normal quantity of bilirubin. This leads to increased excretion of fecal stercobilinogen and urinary urobilinogen (Table 41. Bilirubin in plasma forms a complex with albumin, which cannot be excreted in the urine. Therefore, hemolytic jaundice is acholuric jaundice (absence of bilirubin in urine). Hepatic Jaundice In hepatic jaundice, all three steps of bilirubin metabolism (uptake, conjugation, and excretion) are affected. But as mentioned earlier, the rate-limiting step is excretion, and therefore that may be the most affected. Therefore, not only the conjugation of bilirubin is impaired, but also some amount of conjugated bilirubin is not excreted in bile. The conjugated bilirubin that accumulates in liver cells diffuses across the cell membrane into the bloodstream. Thus, in hepatic jaundice the blood contains excess of bilirubin-albumin complex as diseased liver may not be able to conjugate all the load of bilirubin. Bilirubin released from hemolysis is conjugated in liver and conjugated bilirubin is secreted in bile into intestine. Excess production of bilirubin by hemolysis leads to hemolytic (Prehepatic) jaundice, diseases of liver (defect in conjugation) causes hepatic jaundice, accumulation of bilirubin due to obstruction to flow of bile causes obstructive (posthepatic) jaundice. Functions of liver, Bilirubin metabolism, Pathophysiology of jaundice, Differences in laboratory diagnosis of types of jaundice, Liver function tests, can come as Short Questions. Functional Anatomy Bile is formed in the liver and is excreted through the bile ductules. The bile ductules along with the branches of portal vein and hepatic artery form the portal triad. The cystic duct from gallbladder combines with hepatic duct to form common bile duct. Common bile duct combines with pancreatic duct and opens to second part of duodenum through sphincter of Oddi. Composition of Bile Bile is a greenish yellow fluid formed in the liver and stored in gallbladder. It is composed of water (98%), and solids that mainly include bile salts and pigments and different ions (Table 42. Bile salts Bile pigments Cholesterol Inorganic salts Fatty acids and fat Alkaline phosphatase Cations: Na+, K+, Ca2+, and Mg2+ 2­ 379 Table 42. Hepatic and Gallbladder Bile There are differences between hepatic bile (bile formed in the liver) and gallbladder bile (bile stored in gallbladder) as bile is concentrated and acidified in gallbladder (Table 42. Water absorption is the major mechanism for concentration of bile that occurs secondary to Na+ absorption (secondary active transport). Bile Acids and Salts Bile Acids There are two types of bile acids: primary and secondary. The secondary bile acids are produced in the intestine where intestinal bacteria convert primary bile acids into secondary bile acids. Bile acids are conjugated with taurine or glycine to form taurocholic acid or glycocholic acid. These acids then combine with sodium and potassium salts to form Na+-taurocholate, Na+-glycocholate, K+-taurocholate, and K+-glycocholate, respectively. For their amphipathic (both hydrophilic and hydrophobic domains) property, along with lecithin and cholesterol, bile salts form cylindrical disks, called as micelles (for details, refer the chapter "Principles of Digestion and Absorption: Chapter 51". Lipids are transported in micelles from the lumen to the membrane of intestinal mucosal epithelial cells where micelle dissociates and lipids are absorbed. Along with phospholipids and monoglycerides, they cause emulsification of fat, which is essential for digestion and absorption of fat. Source of bile acid: Bile salts are converted to bile acids in the intestine, which are then absorbed into portal blood. Thus, bile salts are important sources of bile acids that add to the bile acid pool of the body. Absorption of fat-soluble vitamins: Bile salts facilitate absorption of fat soluble vitamins (vitamins A, D, E, and K). Hence, in obstructive jaundice, features of deficiencies of fat soluble vitamins develop. Prevention of gallstone formation: Bile salts along with lecithin solubilize cholesterol. Constipation occurs in conditions of deficiency of delivery of bile into intestine as occurs in obstructive jaundice. Prevention of bacterial growth: Bile maintains pH of intestinal content and prevents overgrowth of bacteria in intestine. Enterohepatic Circulation Bile acids and salts are absorbed from the intestine and re-excreted in the bile, and this cycle is repeated so many times, which is called enterohepatic circulation of bile acids and salts. Functions of Bile Salts Bile salts are primarily responsible for absorption of fat and fat soluble nutrients. Thus, from gut, about 95% of secreted bile salts and bile acids are transferred back to liver via portal circulation, and only 200 to 500 mg/day of bile acids are excreted from stool. Enterohepatic circulation ensures preservation and reutilization of various substances. The substances that undergo enterohepatic circulation include bile salts, bile acids, bile pigments, vitamin D, vitamin B12, thyroxine, drugs, etc. Total amount of bile acids (conjugated and unconjugated, and primary and secondary) in the body ranges from 2 to 4 g. Bile acid is cycled several times a day during meals, so that a small pool of bile acid can efficiently provide enough bile salts to facilitate adequate lipid absorption from small intestine. Though absorption of bile acids and salts from intestine occurs efficiently, some amount is lost with every cycle of passage through intestine. This accounts for loss of about 500 mg of bile acid daily, which is replenished by synthesis of new bile acids from cholesterol. Thus, fecal excretion of bile acid accounts for an efficient medium for loss of body cholesterol. Determinants of Enterohepatic Circulation the major determinants of enterohepatic circulation of bile acids and salts are integrity of intestinal epithelium to reabsorb them and efficiency of hepatocytes to pick them up from portal blood. Integrity of Intestinal Epithelium Bile salts are absorbed mainly in the terminal ileum by an efficient carrier mediated process so that only a 5% of intestinal bile salts enter the colon. Also in the intestine, bacteria deconjugate the bile salts to bile acids, and bile acids are absorbed passively and easily as they are more lipophilic than bile salts. Importance of Enterohepatic Circulation the primary function of enterohepatic circulation of bile acids and salts is to maintain the total bile acid pool of the body. Thus, intestinal absorption of bile acids and salts into portal blood is an important determinant of enterohepatic circulation of these substances. Further, bacteria convert primary bile acids to secondary bile acids that are also absorbed into portal circulation. Therefore, lipid malabsorption occurs in chronic inflammatory conditions of intestine (Clinical Box 42. The ions are transported in a similar way to that of pancreatic extralobular ducts. Modification of Bile in Gallbladder Bile is continuously synthesized and secreted from liver and is stored in the gallbladder. Acidification of bile: the hydrogen ion is secreted from gallbladder epithelial cell into the bile to make the bile acidic. Concentration of bile: H+ is secreted into the lumen of gallbladder in exchange for Na+ (Na+-H+ exchanger). For Na+ transport into the cell, the gradient is created by Na+-K+ pump located in the basolateral membrane of the epithelial cells. Once they reach liver, hepatocytes efficiently pick-up bile salts from hepatic blood, which accounts for removal of more than 80% of portal bile salts. This hepatic uptake of bile salts is an important determinant of secretion of bile salts in the bile. Thus hepatic uptake is the determinant of efficiency of enterohepatic circulation of bile salts. Therefore, inflammation of lower part of small intestine (enteritis) that inhibits absorption of bile salts in intestine results in loss of large quantity of lipid in the stool (due to malabsorption of fat). Similarly, inflammation of liver (hepatitis) impairs the uptake of bile acid and salts from portal blood that in turn decreases their secretion in the bile. Regulation of Bile Secretion Bile secretion is influenced by choleretics and cholagogues. Bile acids are taken up from the sinusoidal blood by transport proteins that are present on the basolateral membrane of the hepatocytes. It should be noted that high concentration of free bile acids destroys the organelles of hepatocytes. Bile acids are conjugated with glycine or taurine and then secreted into the lumen of hepatic canaliculi by facilitated diffusion. The concentration gradient is maintained by formation of micelles in the bile present in the canaliculi. Mechanism of Water and Electrolyte Secretin Water and electrolyte concentration of bile in the bile canaliculi is same with that of plasma. Cholagogues the substances that cause contraction of gallbladder to increase the output of bile from the structure are called cholagogues. Cholecystokinin causes contraction of smooth muscles of gallbladder and empties its contents. Functions of Bile Functions of bile are mainly due to presence of bile salts in it. Bile pigments (bilirubin and biliverdin) are responsible for greenish-yellow coloration of gallbladder that helps to identify the organ especially in small animals.

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