Systemic Physiology Learning Resource Pack 2024 PDF

A LEARNING RESOURCE PACKAGE FOR LECTURE IN SYSTEMIC PHYSIOLOGY COMPILED BY ANNALIE B. PARAGAS, DVM, MPH Associate Professor 1 College of Veterinary Medicine Tarlac Agricultural University...

A LEARNING RESOURCE PACKAGE FOR LECTURE IN SYSTEMIC PHYSIOLOGY COMPILED BY ANNALIE B. PARAGAS, DVM, MPH Associate Professor 1 College of Veterinary Medicine Tarlac Agricultural University 1  Micro-syllabus in Systemic Physiology Course description Vision This course deals on the normal physiology of the TAU as one of the top respiratory, digestive, metabolic, urinary, and body 500 universities in fluid systems. This helps to understand and apply Asia. biological principles and mechanisms underlying health and diseases. Additionally, this will aid future veterinarians: (1) to interpret results for accurate disease diagnosis; (2) prescribe and implement treatment to remedy diseases and abnormalities of animals; (3) formulate and implement agricultural development plans and programs. Furthermore, this discusses also the latest developments in the field of Veterinary Physiology. Credit: 3-3-4 Breakthrough Goals Anchored on the Target Outcomes challenges of the 1. Articulate and discuss the latest developments Sustainable Development in the specific field of practice; Goals for inclusive 2. Effectively communicate orally and in writing growth, TAU will: using both English and Filipino; 1. take lead in 3. Work effectively and independently in multi- innovative teaching disciplinary and multi-cultural teams; methodologies and 4. Generate and share knowledge relevant to appropriate technologies specific fields in the study of Veterinary to create an ideal Physiology; environment to optimize 5. Formulate and implement agricultural learning; development plans and programs; 6. Understand and apply biological principles and 2. advance sustainable mechanisms underlying animal production, agricultural health, and diseases; productivity and improve 7. Interpret results for accurate disease income through diagnosis; and innovation, technology 8. Prescribe and implement treatment to remedy generation, transfer and diseases and abnormalities of animals or training; and prescribe termination of cases, as necessary. 3. use Science, Course Contents Technology and I. Respiratory System Engineering (STE) Functional Anatomy of the mammalian effectively for climate respiratory system change resiliency, Factors affecting respiration and ventilation adaption and Diffusion of respiratory gases agricultural Regulation of Ventilation – neural productivity. control; humoral control Respiratory clearance 2  Non-respiratory functions of the respiratory system Avian respiration II. Urinary System Structure and function of the kidney Formation of urine ▪ Glomerular filtration ▪ Tubular reabsorption and secretion ▪ Autoregulation ▪ Counter-current mechanism Hormones and kidney functions ▪ Anti-diuretic hormone ▪ Angiotensin II ▪ Aldosterone ▪ Parathyroid hormone Micturition ▪ Micturition reflexes ▪ Characteristic of Mammalian urine Renal Clearance Maintenance of acid-base balance Avian renal physiology III. Digestive system The digestive tract and accessory glands Physical and mechanical factors in digestion ▪ Prehension ▪ Mastication ▪ Deglutition ▪ Smooth muscle activity Digestive secretions ▪ Digestion and absorption of carbohydrates, protein and fats ▪ Microbial digestions in the large intestines Ruminant digestion Avian digestion Metabolism of major nutrients – carbohydrate, proteins, fat IV. Temperature regulation in hemeotherms and poikilotherms Teaching and Learning Activities Instructor’s/Professor’s Note/Message Synchronous discussion will be done via online (Google Meet, Google Classroom); Asynchronous discussion will be done at the student’s own pace time (within the prescribed schedule of the specific topic); Student-led/Teacher-led discussion forum will be conducted to encourage students to participate in the discussion (A specific topic will be posted and every student is required to post at least 2 comments regarding the topic posted, this also encourages the student to read and understand 3 the topic posted). Self-gauging quizzes will be posted after each topic. Assessment Strategies 1. Graded discussion forum; 2. During synchronous discussion a paddlet will be used in graded recitation (if possible); 3. Online short quizzes will be conducted to encourage students read the previous topics discussed or the topics in advanced; 4. Reflective journal/Session paper will be given to encourage the students to dig more of the topics, to do research about the topics assigned. 5. Faculty-Marked Assignment will be given and will be graded; and 6. Term exams will be delivered online. Suggested Readings Instructor’s Contact details: Reece, William O. 1997. Physiology of Domestic Animals. Williams and Wilkins, Baltimore [email protected] Swenson, M et al. Duke’s Physiology of Domestic Animals, Cornell University Press, Ithaca, NY Cunningham, JG. 2002. Textbook of Veterinary Physiology. WB Saunders Co., Philadelphia Rhodes, RA and Tanner, GA. 1995. Medical Physiology. Little Brown and Co., Boston. Grading System LECTURE = 60% Quizzes 25% Term Tests (30%) Class Standing (5%) (attendance, participation, interest, and attentiveness) LABORATORY = 40% Activity or exercises (hands on) = 15% Laboratory report= 10% Reporting = 10% Project = 5% PASSING GRADE = 75% 4 Class Policies The course activity will be delivered on a blended scheme (online, offline, face-to-face) or flexible learning strategies. During discussions and topic brainstorming, everyone is encouraged to share their opinions and insights with equal opportunities while complimenting all students with no gender limitations. All students are encouraged to observe online discussion etiquette (muted microphone; and presentable appearance during video conferences). Always use gender-fair language inclusive and free of gender stereotypes and biases. During group reporting, peer teaching, and assigning workshops in groups, all students have equal interactions with each other in an environment free from gender discrimination. All students are encouraged to participate in online/ face-to-face evaluation for the teaching and learning assessment to gauge the skills and knowledge gained during the course administration. The submission bins for the faculty-marked assignments/session papers/reflective journals will be opened at a prescribed range of time. Any late submission will mean a deduction in grade for that activity or may have been internally arranged when needed if reasons are plausible. Everyone will use the school’s email domain in submitting school-related activities and requirements if face-to-face cannot be done. Students are encouraged to consult about the course or specific topics during the class or at designated consultation hours. Attendance of students is called before and after discussion or as needed. Students who will be excused due to health issues or any plausible circumstances that delay their attendance, activities, or submission of requirements in the class should be presented with proof and/or promissory notes (if needed). Always maintain cleanliness and orderliness in the classroom for a conducive learning environment. Incentives will be given to the 5  class when classroom management is continuously maintained at the end of the month. Such incentives will be in the form of merit points and other equivalents after consultation with the class. However, non-compliant with this protocol will be given demerits (points) and other equivalents. Always observe the minimum health protocols. The Passing Grade is 75%. A comprehensive exam for conditional students will be given only to those with a 65% grade, while 64% and below will already be given a failing grade of 5.00. MODULE TITLE PAGE MODULE 01 THE KIDNEYS AND THE URINARY SYSTEM 6 MODULE 02 URINE FORMATION 11 MODULE 03 KIDNEY FUNCTION TESTS 17 MODULE 04 THE COUNTERCURRENT MECHANISM AND 20 HORMONAL REGULATION OF RENAL FUNCTIONS MODULE 05 THE ACID-BASE BALANCE, DISTURBANCES, AND 26 THE AVIAN URINARY SYSTEM MODULE 06 THE DIGESTIVE SYSTEM 32 MODULE 07 THE RUMINANT DIGESTION AND RUMINATION 44 MODULE 08 RUMEN FERMENTATION AND MICROORGANISMS 50 MODULE 09 PROTEIN DIGESTION IN RUMINANTS 58 MODULE 10 THE ABSORPTION AND GASTRIC MOTILITY 61 THE GASTRIC, PANCREATIC, AND BILIARY MODULE 11 67 SECRETIONS THE ENTEROHEPATIC CIRCULATION, CHEMICAL MODULE 12 DIGESTION OF NUTRIENTS, AND LIPID 75 DIGESTION THE MECHANISM OF ABSORPTION, AND AVIAN MODULE 13 82 DIGESTION MODULE 14 THE RESPIRATORY SYSTEM 91 THE GAS LAWS, AND THE MECHANISM OF MODULE 15 94 RESPIRATION ALVEOLAR GAS EXCHANGE AND THE DEAD- MODULE 16 100 SPACE VENTILATION HUMORAL AND MECHANICAL FACTORS MODULE 17 103 AFFECTING RESPIRATION THE BUFFER SYSTEM OF THE BODY, AND MODULE 18 108 AVIAN RESPIRATORY SYSTEM 6  Learning Resource Materials MODULE 01: THE KIDNEYS AND THE URINARY SYSTEM Target Outcomes At the end of the lesson, you are expected to: 1. Distinguish and define the structures and functions of the kidneys; 2. Discuss how blood is filtered in the kidney; 3. Identify the factors that regulate blood filtration; and 4. Know the Principles of Autoregulation of Renal Blood Flow and Filtration Rate. Abstraction THE KIDNEYS AND URINARY SYSTEM Two major functions of the kidneys: Excretion of metabolic waste products. Regulation of the volume and composition of the body’s internal environment, the extracellular fluid (ECF). In this regard it has been said that the composition of the body fluids is determined not by what the mouth takes in but by what the kidneys keep. Other essential functions: Secretion of hormones. Hydrolysis of small peptides. The hormones participate in the regulation of systemic and renal dynamics, red blood cell production, and calcium, phosphorus and bone metabolism. Small peptide hydrolysis conserves amino acids, detoxifies toxic peptides, and regulates effective plasma levels of some peptide hormones. Because of these multiple functions, there are many clinical signs associated with renal disease. MULTIPLE FUNCTIONS OF THE KIDNEYS Excretion of metabolic waste products and foreign chemicals, drugs and hormone metabolites -urea, creatinine, uric acid, end products of hemoglobin breakdown and metabolites of various hormones. Regulation of water and electrolyte balance. Regulation of arterial pressure. Regulation of acid-base balance. Regulation of RBC production. Regulation of 1,25 Dihydroxy Vit D3 production. Gluconeogenesis: Kidneys synthesize glucose from amino acids and other precursors during prolonged fasting. Formation of urine. Concentration of urine and reabsorption of essential electrolytes. Kidneys perform most of their important function by filtering the plasma and removing the substances from the filtrate at variable rates, depending on the needs of the body. Ultimately, they clear unwanted substances from the filtrate by excreting them in the urine while returning substances that are needed back to the blood. ANATOMY OF KIDNEY The two kidneys are located on the posterior wall of the abdomen, outside the peritoneal cavity. 7  The functional unit of the kidney is the nephron. Nephron numbers vary considerably among species and within species and their numbers are relatively constant. The kidney consists of two regions such as outer cortex and an inner region, the medulla. NEPHRON COMPONENTS The glomerular capsule (Bowman’s capsule) is the dilated blind end of the nephron and consists of the invaginated capillary tuft called as the glomerulus. In the mammals the blood from the renal artery is delivered to the afferent arteriole which divides into numerous glomerular capillaries. The capillaries coalesce to form the efferent arteriole which conducts blood away from the glomerulus and is returned to the systemic circulation through the renal vein. The glomerular capsule is lined by a layer of epithelial cells. The area between the glomerular tuft and the Bowman’s capsule is known as the Bowman’s space and it is the site of collection of the glomerular filtrate which is directly funneled into the proximal tubule. The nephron is continued from the glomerular capsule by proximal tubule which is composed of proximal convoluted portion and the proximal straight portion. Convoluted portion is within the cortex and the straight portion extends about half way into the outer medulla. The loop of Henle consist of descending thin limb which is continuous from the proximal straight tubule, the ascending thin limb that terminates at the junction of the inner and outer medulla (cortical nephrons lack a thin ascending limb) and the ascending thick limb that returns to the glomerulus of origin in the cortex and passes between the afferent and efferent arterioles. The distal nephron begins at this point and consist of distal tubule, the connecting tubule, cortical collecting tubule and collecting duct (outer medullary and inner medullary). The distal tubule, connecting tubule and cortical collecting tubule are collectively referred to as distal convoluted tubule. BLOOD SUPPLY Blood flow to the kidneys is normally 22% of the cardiac output. The renal artery enters the kidney and branches to form the interlobar arteries, arcuate arteries, interlobular arteries and afferent arterioles which lead to the glomerular capillaries, where large amount of fluid and solutes (except plasma proteins) are filtered to begin urine formation. The distal ends of the capillaries of each glomerular coalesce to form the efferent arteriole which leads to a second capillary network, the peritubular capillaries surrounding the renal tubules Renal circulation is unique, in that it has two capillary beds: Glomerular capillaries Peri-tubular capillaries, separated by efferent arterioles which help to regulate the hydrostatic pressure. The glomerulus has a high pressure of 60 mm Hg and peritubular capillaries have a low pressure of 13 mm Hg which helps in rapid fluid filtration. The peritubular capillaries empty into vessels of the venous system which run parallel to the arteriolar vessels and progressively form the interlobular vein, arcuate vein, interlobar vein and renal vein. VASA RECTA The peritubular capillaries branches to form the vasa recta into the medulla and lie side by side with the loops of Henle. Like the loops of Henle, the vasa recta return toward the cortex and empty into the cortical veins. They are associated with long looped nephrons. They play an essential role in the formation of concentrated urine. JUXTAGLUMERULAR (JG) APPARATUS When the thick segment of the ascending limb of the loop of Henle returns to its glomerulus of origin in the cortex, it passes in the angle between afferent and efferent arterioles and continues as the distal tubule. The side of the tubule that faces the glomerulus 8  comes in contact with the arterioles, the contact epithelial cells are denser than the other epithelial cells and are collectively called as macula densa. Macula densa marks beginning of the distal tubule. The smooth cells of the afferent and efferent arterioles that make contact with the macula densa are specialized smooth muscle cells and are called as Juxta glomerular cells or Granular cells. Juxta glomerular cells have secretory granules that contain renin, a proteolytic enzyme. The space between the macula densa and the afferent and efferent arterioles and the space between the glomerular capillaries is known as mesangial region/Extra glomerular mesangial cells or Lacis cells. JG cells are involved in feedback mechanism that assist regulation of renal blood flow and glomerular filtrate rate. INNERVATION Innervation to the kidney is provided by fibers from the sympathetic division of the autonomic nervous system which assists in the regulation of renal blood flow (RBF), glomerular filtration rate (GFR), salt and water reabsorption by the nephron. RBF and GFR is brought about by vasoconstriction initiated by reflexes through the vasomotor center in the medulla and pons. Increased sympathetic tone elicits renin secretion from granular cells and enhances sodium reabsorption from nephron segments. TYPES OF NEPHRON Mammalian kidney has two principal types of nephrons and are classified based on Location of their glomeruli Depth of penetration of the loops of Henle into the medulla. Those nephrons with glomeruli in the outer and middle cortices are called cortical nephrons. They are associated with the loop of Henle that extend to the junction of the cortex and medulla or into the outer zone of the medulla: Marine aquatic mammals Those nephrons with glomeruli in the cortex close to the medulla are known as juxtamedullary nephrons. They are associated with loops of Henle that extend deeper into the medulla: Mammals in arid region desert animals such as Kangaroo and rat. GLOMERULAR FILTRATION RATE (GFR) It is the quantity of GF formed each minute in all the nephrons of both the kidneys/kg body weight. In humans it is about 125 ml/min. Total quantity of GFR formed /day = 180 L. Over 99% of the filtrate is reabsorbed in the tubules, the remainder passing into the urine. FILTRATION FRACTION It is the percentage of the renal plasma flow that becomes Glomerular Filtrate. The normal plasma flow through both the kidneys is 650 ml/min but the normal GFR in both the kidneys is 125 ml/min, hence the average filtration fraction is 19%. FACTORS AFFECTING GLOMERULAR FILTRATION RATE Three factors that determine the filtration pressure are Glomerular pressure Plasma colloidal osmotic pressure (COP) Bowman’s capsular pressure Greater the glomerular pressure, greater is the filtration. Greater the plasma COP and Bowman’s capsular pressure, lesser is the filtration. Effect of renal blood flow GFR is affected by the rate of blood flow through the nephrons. Since a very large portion of plasma is filtered through the glomerular membrane, the COP in the glomerulus is high which opposes further filtration. Therefore, a portion of plasma fluid is not filtered until new plasma flows into the glomerulus. Greater the plasma flow, greater the filtration rate. 9  Effect of afferent arteriolar constriction Afferent arteriolar constriction decreases the rate of blood flow into the glomerulus and decreases GFR, causing decreased filtration rate whereas dilatation increases glomerular pressure as well as GFR. Effect of efferent arteriolar constriction Constriction of the efferent arteriole increases the resistance and outflow from the glomeruli, increases the glomerular pressure and also GFR initially. But when blood stagnates in the glomerulus for a prolonged period, increase in plasma COP occurs which causes a fall in GFR. Net effect is slight increase in GFR. Effect of sympathetic stimulation Mild to moderate stimulation of sympathetic nerves causes afferent arteriolar constriction and decreases GFR. Strong sympathetic stimulation causes great reduction in the glomerular blood flow and glomerular pressure resulting in fall of GFR to zero level. Effect of arterial pressure When arterial pressure increases from 100 to 200 mm Hg afferent arteriolar constriction occurs automatically by autoregulation, thus prevents a major rise in glomerular pressure (GP) and GFR increases to only 15-20%. AUTOREGULATION OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION RATE RBF and GFR remains almost relatively constant when the systemic arterial pressure changes from 75 mm Hg to 160 mm Hg. This ability of the RBF and GFR to resist severe changes in the arterial pressure is called as 'autoregulation of RBF and GFR'. It is an intrinsic mechanism which is independent of the nerve supply. Two theories have been proposed to explain autoregulation Myogenic Theory JG Theory Myogenic theory According to this theory, the increase in BP would expand an artery and it would respond by contracting. In this way, RBF would be decreased and glomerular HP reduced. The reduced glomerular HP reduces GFR. A reduction in BP causes less tension and blood vessel would dilate to increase RBF and glomerular HP with subsequent increase in GFR. That is, when arterial pressure rises, arterioles are stretched, once stretched, arterioles contract forcefully. This decreases RBF to normal level. A decrease in arterial pressure dilates the blood vessels which increases RBF and GFR. JG theory Juxta glomerular apparatus (JGA) contains renin (a proteolytic enzyme). Renin is released when: Reduced GFR Reduced glomerular pressure Increased sympathetic stimulation of kidneys The last two occur during low BP and always cause reduced GFR. Reduced GFR causes reduced sodium concentration in the tubular fluid as it flows past the macula densa and this low sodium causes release of renin from JGA. Once renin is released from JG cells it diffuses into the blood of afferent arteriole and circulates throughout the body. In the blood it splits a renin substrate, an alpha 2 globulin to angiotensin I, a decapeptide. Angiotensin I is rapidly converted to angiotensin II by converting enzyme which is present in high concentration in the lungs. Angiotensin II is a powerful vasoconstrictor and causes vasoconstriction throughout the body thereby increasing the BP. Some amount of Angiotensin II is formed in the glomerulus, i.e. in the JG cells. Angiotensin II causes marked constriction of efferent arteriole which increase glomerular pressure and also GFR but decreases RBF. Increase in pressure increases GFR but decrease in blood flow decreases GFR and in effect there is a less change in GFR. Decreased blood flow to peritubular capillaries decreases peritubular pressure, which causes increased tubular reabsorption, so excretion is reduced. When efferent arterioles are constricted, GFR is normal, excretion of waste products such as urea, creatinine is normal. At the same time there is an increase in tubular reabsorption of salt and water. Therefore, effect of angiotensin is to conserve water and salt while allowing normal excretion of waste products. 10  Angiotensin II constricts the efferent arterioles to a greater extent than that of afferent arteriole. Reabsorption of water and salt by renin-angiotensin system helps to control arterial BP. Utilization of Learning Self-gauging assessment: 1. What are the 2 major functions of the kidneys? 2. What is juxtaglomerular apparatus? 3. Differentiate cortical and juxtaglomerular nephrons. 4. Differentiate the Myogenic and JG Theory of Autoregulation of renal blood flow. IMPLICATIONS: _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ 11  Learning Resource Materials MODULE 02: URINE FORMATION Target Outcomes At the end of the lesson, you are expected to: 1. Demonstrate the process of urine formation; 2. Identify the absorptive capabilities of different tubular segments; 3. Recall reabsorption and secretion in different regions of tubules; and 4. Distinguish and define the structures and functions of urinary bladder. Abstraction TUBULOGLOMERULAR FEEDBACK The mechanism of tubuloglomerular feedback (TGF) is also associated with the JG theory of autoregulation. TGF refers to alteration in GFR with changes in the tubular flow rate. It is mediated by the macula densa cells of the JG apparatus. These cells sense changes in the sodium and chloride to their region. If GFR is increased because of increased glomerular HP there will be increase in macula densa flow and sodium and chloride delivery initiates a response that returns GFR and macula densa flow towards the normal by afferent arteriole constriction (which lowers glomerular HP). When renal blood flow falls too low it decreases the GFR thereby, decreases in sodium and chloride delivery to the distal tubule which initiate a signal from macula densa and dilates the afferent arterioles and it increases glomerular blood flow and glomerular pressure. This causes the GFR to increase to normal. FORMATION OF URINE Three processes are involved in the urine formation in the nephrons: Glomerular filtration Tubular reabsorption Tubular secretion GLOMERULAR FILTRATION Glomerular filtrate is the fluid that is filtered through the glomerular membrane into the Bowman’s capsule. Glomerular capillary membrane Glomerular capillaries are relatively impermeable to proteins so that the filtered fluid, glomerular fluid (GF) is essentially protein free and devoid of cellular elements. The glomerular capillary membrane has three layers: Endothelium of the capillary Basement membrane A layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane. The endothelial cells lining the glomerulus are perforated by thousands of small holes called fenestrae. Surrounding the endothelium is the basement membrane composed of a meshwork of collagen and proteoglycan fibrillae which can filter large amount of water and small solutes. The final layer contains epithelial cells called podocytes lining the outer surface of the glomerulus. These cells are not continuous but consists of many finger-like projections which form slit pores through which glomerular filtrate filters. Therefore, GF must pass through three different layers before it enters the Bowman’s capsule. 12  The permeability of the glomerular membrane is 100 to 1000 times as great as that of the usual capillary and is because of the pores of the endothelium which are approximately 100 nm diameter and also slit pores approximately 25 nm wide. Despite the tremendous permeability of glomerular membrane, it has a high degree of selectivity for the sizes of the molecules that it allows to pass. Molecular weight Permeability Example 5000 1.0 Inulin 30,000 0.5 Very small protein 69,000 0.005 Albumin Therefore, plasma proteins are completely impermeable. Reasons for high degree of selectivity Size of the molecule: Pores in the membrane allow molecules with a diameter up to 8 nm. Pores are lined with a strong negative charges and electrostatic repulsion of the protein molecules (proteins are electronegative) prevent their filtration. Dynamics of Glomerular filtrate The energy for the filtration is provided by the heart in the form of hydrostatic pressure of the blood inside the glomerular capillaries and the colloidal osmotic pressure of the fluid within the Bowman’s space through the capillary membrane into the Bowman’s capsule. On the other hand, colloid osmotic pressure in the blood and the hydrostatic pressure in the Bowman’s space oppose filtration. The colloidal osmotic pressure in the Bowman’s capsule is negligible due to very low protein content. The colloidal osmotic pressure in the glomerular capillaries increases, since 1/5th of the fluid portion of the plasma in the capillaries filters into the capsule increases the protein concentration about 20% as blood passes from arterial to venous end of the glomerular capillaries. The colloidal osmotic pressure of the blood entering the capillaries is 28 mm Hg which rises to 36 mm Hg by the time the blood reaches the venous side and so the average colloidal osmotic pressure is 32 mm Hg. Filtration pressure It is the net pressure forcing the fluid through the glomerular membrane equals to the glomerular pressure minus sum of glomerular colloidal osmotic pressure and capsular pressure. For example, If Glomerular Hydrostatic Pressure = 60 mm Hg, Colloidal Osmotic Pressure in glomerulus = 32 mm Hg and capsular pressure (Bowman’s capsule Hydrostatic Pressure) = 18 mm Hg Then, the Filtration pressure = 60-(18+32) = 10 mm Hg. Tubular transport Transport of fluid from the Bowman’s capsule to the renal pelvis is accomplished by a difference in the hydrostatic pressure. Tubular reabsorption involves transport of water and solutes from the tubular fluid to the peritubular capillaries. Tubular secretion It is the transport of solute from the peritubular capillaries to the tubular fluid. TUBULAR REABSORPTION Reabsorption plays a major role than the secretion in the formation of urine. More than 90% of the water in the GF is reabsorbed as it passes through the tubules. Some substances such as sodium, glucose and amino acids are almost completely reabsorbed so that their concentration decreases almost to zero before the fluid becomes urine so that they are conserved by the body and not excreted and lost by the urine. Basic mechanisms of absorption is by two process Active transport Passive transport 13 Active transport through the tubular wall Tubular epithelial cells have a brush border at the luminal surface. It is composed of microvilli which increases surface area of the lumen. The base of the cell rests on the basement membrane. Basal channels in the basement membrane increases the surface area. Epithelial cells are attached to each other near the brush border forming tight junction or zona occludens. Sodium, glucose, amino acid, calcium, potassium, phosphate and urate ions are actively transported. They are transported through carrier proteins. Uniport Transport by a carrier for a single compound (e.g., sodium) and is unidirectional. Symport or co-transport Transport of two compounds on the same carrier in the same direction (e.g., sodium plus glucose, or sodium plus amino acid). Antiport or counter transport Movement of a compound in one direction driven by the movement of a second compound in opposite direction (e.g., Na2+ and H+ antiport). Sodium reabsorption About 65% of Na2+ is reabsorbed in the proximal tubule. The energy required for this mechanism is derived from the Na2+-K+ ATPase (sodium pump) located in the basolateral membrane of the proximal tubule epithelial cells. Electrochemical Gradient Sodium ions are actively transported from the interior of the tubular epithelial cells to the peritubular space across the basal membrane. Therefore, intracellular Na2+ is lowered, creating a chemical gradient for Na 2+ (lumen concentration higher) between the tubular lumen and tubular epithelial cell. It also causes a low negative intracellular electrical potential (-70 mv) which in turn causes the Na2+ to diffuse from the tubular lumen into the cell through the brush border. This mechanism is uniport or unidirectional Na2+ transport. Chloride ion readily diffuses from the tubular lumen to the peritubular space through tight junction between tubular epithelial cells because of transepithelial electrical potential difference (lumen negative) created by Na2+ transport. Antiport or counter transport of sodium ion Diffusion of Na2+ because of electrochemical gradient is coupled through a carrier protein with H+ diffusing in the opposite direction from the cell interior to the tubular lumen. HCO3- in the cell can diffuse through the basolateral membrane to the peritubular space or move into the tubular lumen in counter transport to Cl- diffusion into the cell. Chloride driven sodium ion transport As more of HCO3- is being reabsorbed in to the peritubular space Cl - gradient favors diffusion of Cl- through the leaky tight function from the tubular lumen into the peritubular space and is accompanied by diffusion of Na 2+ in the same direction to maintain electrical neutrality. Glucose and amino acid reabsorption These are reabsorbed by symport or co-transport. They are coupled with specific carriers that require Na2+ binding and diffuse into the cell. Inside the cell Na2+ and glucose or amino acid separates from the carrier. The Na2+ is actively transported by Na2+- K+ ATPase to the peritubular space. Glucose and amino acids are then transported by facilitated diffusion. Passive transport of water and other solutes After the diffusion of solute (Na2+, Cl-, HCO3-, glucose, amino acid) into the peritubular space, an osmotic gradient is established, where by a greater osmotic pressure is present in the peritubular space. Therefore, water diffuses from the peritubular lumen and tubular cells into the peritubular space. As 65% of Na2+ is reabsorbed, similarly 65% of water is reabsorbed from the proximal tubule (an additional amount for other osmotically active substances such as glucose, amino-acid). As water is reabsorbed, urea and other non-actively reabsorbed solutes get concentrated in the tubular lumen. A chemical concentration gradient is established for these substances and they are reabsorbed down their concentrated gradient. The extent of their reabsorption depends on the permeability of the tubular epithelium for the solute. 14  Urea permeability for the proximal tubule is much less than that of water and more than 50% of the amount of urea in the GF continues beyond the proximal tubule. There is no permeability of tubular membrane for reabsorption of creatinine, inulin, mannitol and sucrose and therefore once these are filtered, their total quantity appears in the urine. Reabsorption of proteins and peptides Proteins with a molecular weight of less than 69,000 are reabsorbed in the proximal tubule and not lost in the urine. They are reabsorbed by endocytosis and subsequently degraded by cellular lysosomes to amino acids. The amino acids move from the cell to the peritubular space by facilitated diffusion. Small peptides are hydrolyzed at the luminal brush border of proximal tubule and the resultant amino acids is taken into the cell by co-transport mechanism. TUBULAR SECRETION Several substances are transported from the peritubular capillaries into the interstitial fluid and then to the tubular lumen via the tubular epithelial cells. Antiport of H+ along with Na2+ reabsorption in the proximal tubule and distal tubule. H+ is secreted throughout the nephron. K+ transport is unique, in that it is reabsorbed in some parts of the tubule and secreted in others. It is reabsorbed in the convoluted portion of proximal tubule and secreted in the straight portion of proximal tubule. It is secreted and reabsorbed in the distal nephron. Ammonium ions are synthesized in the epithelial cells and diffuse into the tubular fluid. ABSORPTIVE CAPABILITIES OF DIFFERENT TUBULAR SEGMENTS Proximal tubule: 65 % of the reabsorption and secretion take place. Only 35% of the GF leaves the proximal tubule. Thin segment of Loop of Henle: Permeability of the epithetical cells of descending limb of Loop of Henle is great and occurs by simple diffusion. It is highly permeable to water and moderately permeable to urea and Na2+. Ascending limb of Loop of Henle: It is less permeable to water and more permeable to urea. Thick segment of Loop of Henle and distal tubule They have rudimentary brush border and cells adapted for Na 2+ transport against concentration gradient. They are impermeable to water and urea. Here, active absorption of Na2+ and active secretion of K+ is controlled by aldosterone. Collecting tubule Final concentration of urine takes place in the collecting tubule. It has two functional units, cortical and medullary portion. Cortical portion is impermeable to urea and medullary portion is moderately permeable to urea. Permeability of collecting tubule to water is determined by the concentration of Antidiuretic hormone (ADH) in the blood. Large amount of ADH causes collecting tubule to be highly permeable to water. In the absence of ADH, very little water is reabsorbed. They can secrete H+ into the tubule. REABSORPTION AND SECRETION IN DIFFERENT REGIONS OF TUBULES Water transport is by osmotic diffusion. Proximal tubule: 65% reabsorption Loop of Henle: 15% Distal tubule: 10% Collecting duct: 9.3% Urine: 0.7% Glucose, proteins, amino acids, vitamins and acetoacetate ions are completely reabsorbed by active process in proximal tubule. 50% of urea is reabsorbed. Creatinine is not reabsorbed but some quantities are secreted in proximal tubule. About 86% of urate ions are reabsorbed. Sulphate, phosphate and nitrates are transported similarly like urates. K+ ion is secreted in distal tubule and collecting tubule. 15  H+ ions are actively secreted in proximal tubule, distal tubule and collecting tubule. Transport maximum Substances such as glucose that are actively absorbed by a carrier transport, there is a maximum rate at which they can be reabsorbed. This is known as transport maximum (T m). When Tm is exceeded in the nephron, it appears in the urine, e.g., in Diabetes mellitus, the movement of glucose from the plasma to the cells is impaired because of lack of insulin. Glucose concentration increases causing plasma and tubular loads to increase. When increased tubular load exceeds the availability of the carrier’s molecules for glucose reabsorption, excess glucose flows through the tubules into to the urine. As glucose is retained within the tubules it contributes to an increase in osmotic pressure and therefore water also remains in the tubular fluid. The point at which the glucose first begins to appear in the urine, 175 mg/dl is known as the renal threshold for glucose. The Tm for the kidney is reached when all the nephrons are reabsorbing to their maximum ability. Tm for glucose = 320 mg/min FUNCTIONS OF THE URINARY BLADDER It provides an expandable reservoir for urine, which is continuously flowing from pelvis of the kidney through ureters. Micturition It is the process in which the urinary bladder empties when it becomes filled with urine. Passage of Urine from the kidney to the bladder Urine is secreted continuously though at a varying rate and it passes through the collecting ducts into the pelvis of the kidney and carried to the urinary bladder by the ureters. The ureters contain muscles capable of contraction, which helps in propulsion of urine along the tube into bladder. Each ureter is innervated by both sympathetic and parasympathetic nerves. As urine collects in the pelvis, pressure increases which initiates peristaltic contraction beginning from pelvis and spreading down along the ureters to force urine towards bladder. Parasympathetic stimulation increases frequency and sympathetic stimulation decreases frequency of peristalsis of ureters. Filling and emptying of bladder (Micturition Reflex) At the junction of ureter with bladder, an ureterovesicular valve is present which prevents reflux of urine from bladder. The urinary bladder possesses the power of accommodation to increase in its contents without increase in internal pressures up to about 150 mm H2O. So, as urine enters the bladder, its walls becomes distended. Out flow of urine into the urethra is prevented by sphincters at the neck of the bladder (internal and external sphincters). When the pressure in the bladder reaches 150 mm water, contraction of bladder wall begins, relaxation of sphincter occurs and urination or micturition occurs. Contraction of abdominal muscles and contraction of diaphragm assist the emptying of the bladder. The urinary reflex may be assisted by voluntary effect; may also be opposed voluntarily. This is accompanied by inhibition of spinal centers of micturition and by contraction of external sphincter which surrounds the external part of the urethra. The desire to urinate arises from stimulation of receptors in the wall of the bladder by stretch and contraction of musculature. Nerves from sympathetic and parasympathetic divisions of ANS supply the bladder. The preganglionic sympathetic fibers leave from spinal cord in 2 nd to 4th lumbar nerves to the posterior mesenteric ganglion and postganglionic fibers reach the bladder through hypogastric nerves. In all mammals, parasympathetic nerves cause contraction of whole bladder and they are main motor nerves. They are inhibitory to internal sphincter. Complete emptying of the bladder depends upon maintenance of bladder muscle contraction and sphincter relaxation. This is achieved by two reflex systems. Receptors are present in the bladder walls that are stimulated during contraction of urinary bladder. Another reflex arises from receptors in the wall of urethra. Urine flow through urethra helps to maintain bladder contraction and relaxation of external sphincter. 16  The tone of the bladder decreases as the bladder becomes emptied of its contents and this is accompanied by contraction of sphincter. The cessation of micturition involves voluntary control and voluntary regulation. Utilization of Learning Self-gauging assessment: 1. Discuss the 3 phases of urine formation. 2. How micturition reflex occurs? 3. Illustrate the flow of urine from the kidney to the urinary bladder. IMPLICATIONS: _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ 17  Learning Resource Materials MODULE 03: KIDNEY FUNCTION TESTS Target Outcomes At the end of the lesson, you are expected to: 1. Distinguish uremia or azotemia; 2. Identify the test required to detect functional disorders of the kidneys; 3. Discuss the renal mechanism of urine formation; and 4. Identify hyperosmolality of the medullary fluid. Abstraction UREMIA OR AZOTEMIA Urea is the chief nitrogenous end product of protein metabolism and is excreted by the kidneys in the urine of mammals. It is also found in the blood and lymph. Uremia is a toxic condition that occurs due to retention of urea is the blood. It results due to Renal failure. Increased production of urea in the liver due to high protein diet, drugs, increased breakdown of protein etc. Decreased elimination of urea due to reduced blood flow to kidney, obstruction of urinary tract etc. Dehydration Chronic infection of the kidney. The symptoms of uremia are lethargy, depression, nausea, vomiting, deep breathing, dizziness, coma and convulsions. In these cases, there is usually a smell of urine in all the animal’s secretions. TERMINOLOGIES Diuresis: Increased urine formation. Polyuria: Increased excretion of urine. It may be due to the deficiency of ADH. Oliguria: Reduced excretion of urine Anuria: Complete cessation of urine formation. Dysuria: Difficult or painful micturition. Stranguria: Slow dropwise painful discharge of urine caused by spasm of urethra and bladder. KIDNEY FUNCTION TESTS Renal clearance is the measurement of the kidney’s ability to remove substances from the plasma. Clearance measurements are used to determine Renal Blood Flow (RBF), Renal Plasma Flow (RPF), Glomerular Filtration Rate (GFR), Filtration Fraction (FF) and how different substances are handled by the kidney tubules (reabsorbed or secreted) and to compare the kidney function values for diagnostic purposes. PLASMA CLEARANCE It is used to express the ability of the kidneys to clean or clear the plasma of various substances. e.g., If the plasma passing through the kidneys contains 1 mg of a substance in each ml and 1 mg of this substance is also excreted into the urine each minute, then 1 ml/min of the plasma is cleared of the substance. Plasma clearance is an excellent measure of kidney function and the clearance rate of different substances are determined by analyzing the concentration of substance simultaneously in plasma and urine and measuring the rate of urine formation. 18 INULIN CLEARANCE AS AN ESTIMATE OF GFR A substance to measure GFR must be freely filtered at the glomerulus and should not be reabsorbed or secreted by the tubular epithelium after it enters the nephron. Inulin, a fructose polysaccharide is the substance that is most commonly used. Mannitol, is another polysaccharide used to estimate GFR. CREATININE CLEARANCE In clinical conditions it can be used to measure GFR and kidney functions. Creatinine is freely filtered and not reabsorbed by the tubules. In some species (not in dogs) about 10% is secreted by the tubules. It can’t be used in birds because creatinine is either secreted or reabsorbed from the tubules to a greater extent. MEASUREMENT OF RPF The substance used must be freely filtered at the glomerulus and must not be reabsorbed from the tubular lumen and must be secreted by the tubular epithelium so that all of the substances in the blood perfusing the tubules is removed before the blood leaves the kidney. Therefore, if all the substance in the plasma that perfuses the kidneys is excreted in the urine the rate of its excretion is the same as its plasma load. Para Amino Hippuric acid (PAH) is used to measure RPF. PLASMA LOAD AND TUBULAR LOAD Plasma load of a substance is the total amount of substance in the plasma that passes through the kidneys each minute. For example, if the concentration of glucose in the plasma is 100 mg/100 ml and 600 ml of plasma passes through both the kidneys each minute, then the plasma load of glucose is 600 mg/min. A fraction of plasma load that is filtered as GF is referred to as tubular load. For example, if 125 ml of GF is formed each minute with a glucose concentration of 100 mg% then the tubular load of glucose is 125 mg (100 x 1.25) glucose/min. RENAL MECHANISM OF URINE FORMATION Renal mechanism of concentrated and dilute urine formation Concentrated urine is formed by passive water reabsorption from the tubules while many solutes in the tubular fluid are absorbed by active process. Dilute urine is formed by absorption of solutes alone and excretion of water in the urine. Dilution or concentration of urine depends on: Hypertonicity/osmolality of the interstitial fluid in the renal medulla. Dilution of the tubular fluid by the thick ascending limb and distal tubules by solute reabsorption which allows formation of dilute urine. Variation in the water permeability of collecting ducts due to ADH, which determines the final concentration of urine. For concentration of urine, there is generation of hypertonic medullary fluid and increase water reabsorption in the distal tubule. For generating hypertonic medullary fluid, two factors are essential: Reabsorption of osmotically active substance by the tubules into the medulla. Removal of water from the interstitium by the vasa recta. These two factors are produced by counter current mechanism. HYPEROSMOLALITY OF THE MEDULLARY FLUID Normal osmolality of the GF as it enters the proximal tubule is 300 milli osm/L. But osmolality in the medullary interstitial fluid is higher reaching a maximum in the inner most regions of the medulla, it increases from 300 milli osm/L to 1200 milli osm/L. The cause of this increased osmolality is the active transport of both sodium and chloride out of the Loop of Henle’s ascending limb and slight reabsorption of sodium actively from the collecting tubule into the interstitial fluid. Also, the cause for accumulation of sodium chloride in medulla is: 19  Sluggish blood flow through vasa recta which helps to prevent removal of sodium chloride from the interstitial fluid. Presence of countercurrent mechanism in the Loop of Henle and vasa recta. Utilization of Learning Self-gauging assessment: 1. Differentiate uremia and azotemia. 2. Define diuresis, polyuria, anuria, dysuria, and stranguria. 3. What is renal plasma flow? 4. Discuss the renal mechanism of urine formation. IMPLICATIONS: _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ 20  Learning Resource Materials MODULE 04: THE COUNTERCURRENT MECHANISM AND HORMONAL REGULATION OF RENAL FUNCTIONS Target Outcomes At the end of the lesson, you are expected to: 1. Distinguish the permeability of tubules; 2. Discuss the countercurrent mechanism; 3. Trace the excretion of diluted and concentrated urine; and 4. Enumerate different buffers of the body. Abstraction PERMEABILITY OF THE TUBULES Descending limb of Loop of Henle: High permeability for water and no permeability for sodium, chloride and urea. Ascending thin limb of Loop of Henle: No permeability for water, highly permeable to sodium, chloride and moderately permeable to urea. Ascending thick limb of Loop of Henle: Permeable to sodium, chloride, low permeability to water and urea. Distal tubule: Permeable to sodium, chloride and low permeability for water and urea. Cortical collecting tubule, outer medullary collecting duct and inner medullary collecting duct: Sodium reabsorption is stimulated by aldosterone and water and urea reabsorption by ADH. COUNTERCURRENT MECHANISM A counter current system of tubules or vessels exists where the inflow of fluid runs parallel to, counter to, and in close proximity to the outflow for some distance. These characteristics are common to the anatomical arrangements of the Loops of Henle and vasa recta. In the kidney, two counter current systems operate. Counter current multiplier - Loops of Henle Counter current exchanger – Vasa recta Counter current multiplier The ascending thick limb of the Loop of Henle is permeable to solutes and so the solutes diffuse into the medullary interstitial fluid with retention of water in the tubule, thereby diluting the tubular fluid. This creates a small osmotic gradient between the tubular and peritubular fluids (interstitial fluid). This osmotic gradient is being multiplied vertically by counter current flow in the descending thin limb (permeable for water and not for solutes). Water diffuses from the lumen of the descending thin limb into the interstitial fluid. Therefore, the tubular fluid of the descending thin limb increases in osmotic concentration as it descends to the inner most region of the medulla. When thin tubular fluid enters the ascending thin limb (permeable for solute and not for water), sodium chloride diffuses readily outward into the inner medullary interstitial fluid and urea diffuses inward into the tubular fluid. Continued active secretion by the ascending thick limb, concentration of tubular fluid in the descending thin limb and diffusion from the lumen of the ascending thin limb into the medullary interstitial fluid establishes a vertical osmotic gradient. Therefore, each time sodium chloride makes the circuit around the Loop of Henle, this multiple the concentration of sodium chloride in the medulla and hence, Loop of Henle is called as counter current multiplier. Countercurrent exchanger - Vasa recta It is a counter current system in which transport between the outflow and inflow is entirely passive. Vasa recta is permeable to water and solutes throughout their length. 21  In the descending limb of the vasa recta, water is drawn by osmosis from the plasma of vasa recta to the hyperosmotic peritubular fluid (created by counter current multiplier) and the solutes diffuse from the peritubular fluid into the vasa recta. In the ascending limb, solutes diffuse back into the peritubular fluid and water is drawn by osmosis back into the vasa recta. Net result is that the solutes responsible for medullary gradient are mostly retained in the medulla and the vasa recta carry only slightly more solutes than are brought to them. Blood flow in the vasa recta is sluggish because an increased rate of medullary blood flow results in decreased time required for diffusion of solute from the ascending limb back to peritubular fluid resulting in gradual loss or wash out of medullary gradient. All the excess salt removed from the interstitial fluid has to be replaced to maintain an osmotic gradient. Recirculation of urea It is a mechanism for concentration of urea in the medulla. Urea is concentrated in collecting tubule and diffuses through the walls of collecting tubule into the medullary interstitial fluid. From there, it is reabsorbed in the Loop of Henle and flows with tubular fluid in the ascending limb through distal tubule into collecting tubule and again out of the collecting tubule into the medullary interstitial fluid. Urea circulates several times before it flows into the urine and it causes urea to accumulate in high concentration in medullary interstitium. This counter current multiplier system helps in concentration of urine and also ensures constant excretion of urea when urine output is low. EXCRETION OF DILUTED URINE When there is excess of water in the body and a reduction in plasma osmolarity, kidneys can excrete a dilute urine with a concentration as low as 50 mOsm/L. This can be achieved by reabsorbing only the solutes and not water in the distal parts of the nephron. The total amount of solute excreted remains constant but the urine formed is very dilute and urine osmolarity decreases from 600 to about 100 mOsm/L. The glomerular filtrate initially formed has the osmolarity similar to that of plasma (300 mOsm/L). In order to excrete excess water it is necessary to dilute the filtrate as it passes along the tubule which is achieved by reabsorption of solutes to a greater extent than water. As the fluid flows through the proximal tubule solutes and water are reabsorbed in equal amount and there is a little change in osmolarity but when it reaches down the descending limb of loop of Henle water is reabsorbed by osmosis and the tubular fluid reaches the osmolarity of renal medulla, i.e. it becomes hyperosmotic. In the ascending limb of loop of Henle sodium, potassium and chloride are actively reabsorbed. Therefore, the fluid becomes dilute as it flows to distal tubule with osmolarity decreasing to 100 mOsm/L (osmolarity is one third of that of plasma). When the fluid passes to late distal tubule and collecting tubule there is little reabsorption of sodium chloride. In the absence of ADH, collecting tubule is impermeable to water and additional reabsorption of solutes causes tubular fluid to become even more dilute, decreasing its osmolarity to as low as 50 mOsm/L. Therefore, failure of reabsorption of water and continued reabsorption of solutes leads to a large volume of dilute urine. EXCRETION OF CONCENTRATED URINE For formation of a concentrated urine two basic requirements are essential High level of ADH which increases the permeability of distal tubule and collecting tubule to water. High osmolarity of the renal medullary fluid which provides osmotic gradient for reabsorption of water in the presence of ADH. When the tubular fluid leaves the loop of Henle and flows into the distal convoluted tubule in the renal medulla, fluid is dilute with a osmolarity of 100 mOsm/L. As fluid flows into the cortical collecting tubule, the amount of water reabsorption is dependent on plasma concentration of ADH. In the presence of high concentration of ADH the cortical collecting tubule becomes highly permeable to water and large amounts of water are reabsorbed. 22  As the fluid flows into the medullary collecting tubule there is further water reabsorption and when the fluid reaches the end of the collecting ducts the osmolarity reaches 1200 mOsm/L which is similar to renal medullary osmolarity. Therefore, by reabsorbing as much as water as possible, kidneys form a highly concentrated urine excreting normal amount of solutes in urine and increasing the ECF volume. HORMONAL REGULATION OF RENAL FUNCTION ADH and water conservation ADH is synthesized in the cell bodies of hypothalamic nuclei (supraoptic nuclei) and transported to nerve fiber endings in the posterior lobe of the pituitary where it is stored in the secretory granules. Its release in the blood is controlled by osmoreceptors in the hypothalamus that are close to the supraoptic nuclei. It regulates water conservation. Increase in plasma osmolality stimulates osmoreceptors in the hypothalamus causing release of ADH which decreases the ECF volume. Fear and pain also cause release of ADH. Aldosterone Adrenal cortex regulates K+ and Na+ concentration. It acts on tubules causing Na+ reabsorption and K+ excretion. Aldosterone increases Na+ reabsorption from distal tubules by increasing Na+ transport protein; salt free diet causes increased aldosterone secretion resulting in increased Na reabsorption. Renin - Angiotensin system Renin is activated by reduced circulating blood volume as in hemorrhage. Decreased sodium concentration in the distal convoluted tubule and sympathetic stimulation also causes release of renin. Parathyroid hormone Ca2+ and PO4 excretion in urine is regulated at the proximal tubule by the action of parathyroid and thyrocalcitonin from thyroid. Parathyroid hormone (PTH) causes decrease in PO4 reabsorption and increase in PO4 excretion in urine. PTH increases mobilization of Ca2+ from bone and absorption from intestine resulting in increased plasma Ca2+ level and decreased Ca++ excretion. Atrial natriuretic peptide Myocardial cells of the atria release the ANP when the atria are stretched during high volume of blood. It has the following functions. Increases the GFR by causing vasodilatation of afferent arterioles and vasoconstriction of efferent arterioles. Inhibits angiotensin II stimulated absorption of Na+ and water in proximal tubules. Reduces water reabsorption in collecting tubules. Inhibits aldosterone release. Decreases the response of the collecting tubules and collecting ducts to ADH. Local hormones Erythropoietin produced from kidney regulates erythropoiesis. Renin is produced from kidney. Prostaglandin from kidney acts as blood pressure lowering agents. PGE is natriuretic. FUNDAMENTALS OF ACID-BASE BALANCE The normal blood pH is 7.4. Maintenance of normal blood and extracellular pH within the narrow limits is essential for homeostasis. The pH usually refers to the hydrogen ion (H+) concentration and has a widespread effect on the function of the body systems. Any disturbance in the H+ ion concentration leads to imbalance of pH. When pH rises above the optimal value it is referred to as alkalosis and if pH drops below optimum level it is referred as acidosis. Regulation of hydrogen ion concentration Three primary buffer systems are involved in regulation of H + ion concentration in the body fluids to prevent alkalosis or acidosis. Chemical acid base buffer systems 23  Respiratory regulation of acid base balance Renal control of acid base balance CHEMICAL ACID-BASE BUFFER SYSTEMS When there is a change in the H+ ion concentration, the body fluids react immediately to minimize the change. Chemical buffers act by converting either strong acids or bases into weaker acids or bases. The various chemical buffers are: Bicarbonate This is the most important buffer system in the body. Bicarbonate combines with H+ ions to form carbonic acid in the tubular fluid, which then dissociates to CO 2 and H20. The CO2 formed is removed by the lungs and the HCO 3- formed in the cells is reabsorbed from the filtrate to the blood. Phosphate buffer It plays a major role in buffering renal tubular fluid and ICF. The two main elements of the phosphate buffer are HPO42- (base) and H2PO4- (weak acid). Hydrogen ions from strong acids are captured by converting a weak base to a weak acid and strong base captured by conversion of a weak acid to a weak base. Protein buffer It is an intracellular buffer present in high concentrations in the blood. Hemoglobin molecule forms the second most important blood buffer and is present in the form of proteinate ions (Hb-). These basic ions, with their weak acids (HHb) form a buffer pair. When an acid is added to the blood, (IMAGEEEEEE) This reaction shifts to the right and the ratio of base to acid is decreased. Hemoglobin is a powerful buffer and it binds with protein, CO 2 and H+ ions. In the tissues CO2 passes into the RBC where it combines with water to form carbonic acid which is catalyzed by the enzyme carbonic anhydrase. Carbonic acid then dissociates into HCO3- and H+ ions. The H+ ions binds to hemoglobin to form HHb and the HCO3- ions passes back to the plasma in exchange for chloride ions. In the lungs this process is reversed where in H+ ions bind to hemoglobin and recombine with bicarbonate to form CO2 which passes into the alveoli. Ammonia buffer system Ammonia is formed by the hydrolysis of glutamine in the presence of enzyme glutaminase in the tubular cells which freely diffuses into luminal fluid and continues with H+ ions to form NH4+ ions. This NH4+ ions combine with chloride ions and is excreted as ammonium chloride in the urine. RESPIRATORY REGULATION OF ACID-BASE BALANCE The respiratory system acts as the second line of defense against acid base disturbances. An increase in PCO2 of ECF, decreases the pH, while a decrease in PCO2, increases the pH. Therefore, by adjusting the PCO2, the lungs effectively regulate the H+ ion concentration of the ECF. An increase in ventilation removes CO2 from ECF thereby reducing the H+ ion concentration. Similarly, a decrease in ventilation, increases CO 2 thus increasing H+ ion concentration in ECF. Arterial PCO2 is inversely proportional to alveolar ventilation, i.e., if alveolar ventilation falls, PCO2 rises. Therefore, relatively small changes in ventilation has a profound effect on H+ ion concentration and pH. Respiratory system acts as a typical negative feedback controller of H + ion concentration. An increase in the H+ concentration above the normal, stimulates the respiratory system and alveolar ventilation increases. This decreases the PCO 2 in ECF and reduces H+ ions concentration back to normal. RENAL CONTROL OF ACID-BASE BALANCE The kidneys regulate acid-base balance by excreting either an acidic or basic urine. Excretion of either an acidic or a basic urine removes acids or basic from the ECF. Large numbers of HCO3- ions are filtered in the urine and if they are excreted into the urine, it removes base from the blood. Similarly, large numbers of H + ions are secreted into the urine, and if they are excreted, it results in loss of acid from the blood. If more HCO3- ions are filtered than the H+ secreted, there will be net loss of base from ECF. The kidneys regulate ECF H+ ions through three basic mechanisms: Tubular Secretion of H+ ions Reabsorption of filtered bicarbonate ions 24  Combination of excess H+ ions with phosphate and amino buffers Tubular secretion of H+ ions H+ ions are secreted in the proximal tubule, thick ascending loop of Henle and distal tubule by sodium hydrogen counter transport. This occurs by means of active transport of sodium ions into the cell and H+ ions from the tubular cell into the tubular lumen against the concentration gradient provided by sodium-potassium ATP pump. For each H+ ion secreted, one HCO3- ion is reabsorbed. When CO2 diffuses into the tubular cells, formed by metabolism, CO2 combines with water, forms H2CO3 which dissociates into HCO3- and H+ ions. H+ ions are secreted from the cell into the lumen by sodium-hydrogen counter transport. The sodium moves into the cell by concentration gradient established by sodium-potassium ATPase pump in the basolateral membrane. H+ ions are also secreted in the distal tubule and collecting ducts and transported through H + pump by H+ ATPase mechanism. Reabsorption of filtered bicarbonates The filtered bicarbonate ions are not easily reabsorbed across the tubular membrane. The bicarbonates combine with H+ ions to form H2CO3 which then dissociates to form Co2 and H2O. This CO2 moves across the tubular membrane and diffuses immediately into the tubular cell. Inside the cell, it combines with H2O to from H2CO3 in the presence of carbonic anhydrase and H2Co3 dissociate to HCO3- and H+ ion. Therefore, for energy H+ ion formed in the tubular epithelial cells, a HCO3- ion is formed and reabsorbed into the blood. Combination of excess H+ with phosphate buffer When excess of H+ ions are secreted, only a small fraction of is excreted in the ionic form (H+) in the urine and the remaining H+ ions combines with buffers such as phosphate and ammonia buffer in the tubular fluid as urine can be acidified to a pH of about 4.5. The phosphate buffer system is composed of HPO42- and H2PO4 -. Both are concentrated in the tubular fluid because of poor reabsorption. Excess H + ions combines with HPO42- to form H2PO4 which in turn are excreted as sodium salt (NaH2PO4). Combination of excess H+ with ammonia buffer system This buffer system is composed of ammonia (NH 3) and ammonium ion (NH4+). Ammonium ion is synthesized from glutamine which is actively transported into the tubular epithelial cells. Inside the cell, glutamine is metabolized to form NH 4+ and two HCO3 - ions. The NH4+ is secreted into the tubular lumen by countercurrent mechanism in exchange for sodium which is reabsorbed. The HCO3- moves across the basolateral membrane along with reabsorbed Na+ into the blood. Therefore, for each molecule of glutamine metabolized in the proximal tubule, two NH4+ ions are secreted into the urine and two HCO 3 - ions are reabsorbed into the blood. In the collecting tubule, formation of NH 4+ ions occur by a combination of NH3 (ammonia) with H+ ions and then excreted as NH4+. The collecting ducts are permeable to NH3 and form NH4+. Hydrogen ions react with NH3 and form NH4+. For each NH4+ excreted, one HCO3- reabsorbed in to the blood. ELECTROLYTES Sodium / Potassium: Sodium reabsorption and H+ ion excretion is interlinked. Sodium reabsorption is controlled by the hormone, aldosterone and ion exchange proteins that exchange sodium for H+ ions or K+ ions. Therefore, the changes in aldosterone secretion may influence acid-base balance. Chloride: The bicarbonate and chloride ions are the two abundant negative ions in the plasma. In order to maintain electroneutrality any change in chloride must be accompanied by opposite change in bicarbonate concentration. Therefore, chloride concentration may also influence acid base balance. Utilization of Learning Self-gauging assessment: 1. How recirculation of urea occurs? 2. Discuss the renin-angiotensin system. 3. How does renal control of acid-base balance occur? 25  4. How does respiratory control or regulation of acid-base balance occur? IMPLICATIONS: _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ 26  Learning Resource Materials MODULE 05: THE ACID-BASE BALANCE, DISTURBANCES, AND THE AVIAN URINARY SYSTEM Target Outcomes At the end of the lesson, you are expected to: 1. Discuss how kidneys play a major role in maintaining pH of the blood; 2. Discuss how the maintenance of fluids and electrolytes balance by the kidneys during dehydration; 3. Identify the structure of kidneys in bird; and 4. Discuss the formation of urine in birds. Abstraction ACID-BASE BALANCE DISTURBANCES The pH of the ECF is determined by the rate of conjugate base to their weak acids. The total amount of buffer base in whole blood including HCO 3, Hb and other bases of lesser importance is called buffer base (B.B). These bases are known as metabolic components determining blood pH. Acid base disturbance involves either the gain or loss of strong acid or the gain or loss of base (Cl- or HCO3-) by the ECF. Metabolic acidosis The gain of strong acid or loss of base from the ECF is known as metabolic acidosis. Acidemia will be present in metabolic acidosis. It occurs in: Ketosis. Diabetes mellitus in which ß hydroxy butyric acid, acetone, acetoacetic acid is produced. Renal acidosis in which there is failure of HCO3- reabsorption and loss in the urine. Diarrhea where pancreatic juice containing HCO3 is not reabsorbed and is lost. In all these cases, HCO3- falls either as a result of a reaction with acid or due to direct loss from ECF and pH falls. This results in fall of all blood buffer bases. Usually there is no change in plasma PCO2. However, a fall in pH results in increased alveolar ventilation and therefore a fall in PCO2. Decreased PCO2 will bring the ratio of conjugate base to weak acid back to normal. However, the total bases will be less than normal and this requires renal correction - the excretion of H+ and restoration of plasma HCO3-. The acidemia stimulates secretion of H+ ion by the renal tubule. This ensures reabsorption of all HCO3 ions from tubular fluid and the excess H+ ions will begin to acidify the urine. For each H+ ion secreted, one HCO3 will be reabsorbed into the plasma. This holds good for short-term stress and in severe conditions, therapeutic action is required. Metabolic alkalosis This process involves the gain of base (OH or HCO 3 ions) or loss of strong acid by ECF. Metabolic alkalosis is present in Persistent vomiting, in which gastric acid is lost from the body. K+ deficiency in which renal tubules secretes large amount of H+ ions into urine. Injection of HCO3 solutions. In all these cases, there is an increase in HCO3 - in ECF, resulting in increased base content. The response of the body is opposite to the one observed in metabolic acidosis. Alkalemia results in rise in pH which will depress pulmonary ventilation and PCO2 will rise. This respiratory compensation thus will bring pH back to normal. Renal correction consists of decreased secretion of pH ions and so increased excretion of HCO3- ions. Respiratory acidosis 27  If excretion of CO2 by the lungs falls below the rate of CO2 production in the body, respiratory acidosis develops. There will be an increase in blood PCO 2 (hypercapnia) and the primary defect will be in the inability of lungs to expire CO2 at a normal rate. This may be due to Depression of respiratory centers in CNS. Abnormality of chest wall or respiratory muscles which prevents enlargement of thorax. Obstruction to gas movement in lungs. A rise in PCO2 causes increase in H2CO3 and buffer reaction prevents the fall of pH caused by rise in H2CO3. Renal compensation then follows. Low pH stimulates secretion of H + into urine with a rise in plasma HCO3-. Respiratory alkalosis When alveolar hyperventilation occurs, the expiration of CO 2 may exceed the rate of its production within the body and respiratory alkalosis develops. There will be low plasma PCO2 (hypocapnia) and alkalemia. Hyperventilation is caused by abnormal stimulus to respiratory centers either directly as in NH3 toxicity or through hypoxemia acting through peripheral chemoreceptors. Buffer reaction follows: Thus, HCO3 falls and Hb rises. The renal compensation begins, alkalemia depresses H+ ion secretion by renal tubules and excretion of filtered HCO3 rises. This results in further fall of plasma HCO3 and the ratio of HCO3 to H2CO3 moves back to normal. THIRST AND DEHYDRATION Regulation of fluid by the body is necessary to maintain homeostasis. If the water or electrolyte equilibrium is affected, many body functions fail to proceed at normal rates. Water Water is a major constituent of all living things. Most of the ions and molecules that make up living matter have chemical and physical relationships with water. The total body water content varies among different species, age, sex, nutritional factors etc. Water content is highest in the new born animal and declines as age advances. An adult contains 60% of water by weight depending upon age and the amount of body fat. Body fat is inversely proportional to the body water content. For example, a very lean animal will contain 70% of water whereas very fat animal will have only 40% of total body water. Body fluid Compartments Body fluid is present in three different compartments namely, intracellular fluid and extracellular fluid, which in turn is divided into interstitial fluid and plasma. In a lean animal, 50% of water is present intracellular, 15% in the interstitial spaces and 5% in the blood plasma. Apart from this, water is also present in the transcellular fluids such as in CSF, aqueous humor of the eye, synovial fluids, urine, bile etc. Water molecules can rapidly penetrate most of the cell membrane. If an osmotic or hydrostatic pressure gradient exists between body fluid compartments, a shift of water will occur. Addition of an isotonic NaCl solution to the ECF causes equal distribution of water extracellularly and intracellularly. If a hypertonic NaCl solution is added, water would begin to shift into the plasma, while, an addition of hypotonic NaCl solution shifts the water into the cell. Water balance The total amount of water in the body almost remains relatively constant. The body gains water either by ingestion or as end product of cellular metabolism. Similarly, loss of water occurs in urine, from the skin, expired gases, feces etc. THIRST Loss of water from the body is continuous and when there is deficiency of water, specific controls of water intake act to correct the deficit. Water deprivation causes the sensation of thirst and drive to drink water. Several mechanisms aid in the control of the amount of water to be ingested so that it equals the deficit of body water. 28  A decrease in body water causes thirst which is characterized by dryness of the throat and mouth due to decreased salivary secretion. The center for thirst and drinking behavior is located in the hypothalamus of the brain. Water deficiency causes a rise in osmotic and sodium concentration in the ECF and a decrease in the circulating fluid volume together with a fall in BP. A fall in the BP is detected by the baroreceptors and the renin relating cells of the kidney which stimulates the thirst center in the hypothalamus. As a result, thirst and drinking of water occurs. A fall in arterial BP alone also causes the release of renin from the juxta glomerular cells of the afferent arterioles of the kidney glomeruli. Renin acts on angiotensinogen to form angiotensin I, which in turn in is converted to angiotensin II by the converting enzyme. In most of the animal’s angiotensin II causes an increase in drinking water. During water deprivation, excretion of water by the kidney is controlled primarily by the Antidiuretic Hormone (ADH) secreted from the posterior pituitary gland. ADH acts on the nephrons of the kidney and causes increased reabsorption of water thereby decreasing the excretion of water with urine. The oxidation of food stuffs also yields some amount of water. The oxidation of each gram of carbohydrate, fat and protein yields about 0.6 ml, 1.1 ml and 0.4 ml of water. This metabolic water constitutes 5 to 10% of the total water intake in animals. DEHYDRATION Dehydration in the animals results due to reduced or absence of intake of water and continuous loss of body water. Dehydration involves both loss of water and electrolytes. The process of dehydration may be slow or rapid depending on the relative rates of water and electrolyte loss. In a simple dehydration due to lack of water under moderate environmental conditions, causes the animals to seek and drink water. There will be a decrease in urine volume output. These changes can be seen when the dehydration is about 1-2% of the body weight. Severe dehydration occurs when the water loss is 10% of the body weight. The immediate source of water lost from the body is the ECF. If the rate of water loss is very rapid, there is drastic reduction in ECF volume. In slow dehydration, there will be a shift of water from the cells into the ECF. During water deprivation loss of water from the body causes an increase in ECF osmolality and a decrease in ECF volume. This stimulates the drinking behavior and a reduced urine output. Electrolytes are also excreted from the body in proportion to water loss in order to prevent a further rise in osmoconcentration. In early dehydration, sodium chloride is excreted in the urine. There is a shift of intracellular water to extracellular fluid. Cellular potassium is also excreted in the urine. Therefore, after a long period of dehydration depletion of both water and primary electrolytes occurs. In human, the limit to which the water can be lost is about 15-25% of the body weight before death occurs. Adaptation to water lack Some of the species that are found in the desert regions such as camel, donkey, kangaroo rats etc., have acquired adaptation to resist water lack. During high summer temperature, these animals have to expend increased amount of water to control their body temperature in the desert regions as there is little amount of rainfall and natural vegetation which contains less water. Under these conditions, the animals have to obtain water either through vegetation or through metabolic water. The water obtained through these mechanisms are small as the actual amount of water formed from the oxidation of fat, carbohydrates and protein are 0.12 g/kcal, 0.14 kg/Kcal and 0.10 g/kcal. The camel has a remarkable ability to conserve water and can withstand a water loss of 25%. During the day when the heat stress is greatest, the camel can rise its body temperature thereby storing heat and saving water. During the cooler night this stored heat is dissipated and the body temperature is brought back to normal. The camel’s summer fur also aids in reducing the solar heat gain. Camel conserves water by excreting dry feces. The water lost through respiration also is very low in camels because of their ability to reduce the relative humidity of expired air to below 100%. This is due to the hygroscopic nature of the nasal secretions. The camel also has the 29  ability to rehydrate rapidly as it can ingest 1/4 th of its body weight as water in a few minutes. The oval biconcave RBCs of the camel are highly resistant to osmotic hemolysis. The donkeys can also withstand dehydration up to 30% and can rehydrate rapidly by drinking 20.5 liters of water in 2.5 minutes. Sheep also has remarkable ability to withstand heat stress and water lack. It can resist 30% dehydration and minimize solar heat absorption by increasing the wool surface temperature up to 87ºC. It dissipates heat by means of panting. ELECTROLYTES An electrolyte in any chemical that dissociates to ions when dissolved in a solution. Ions can be positively charged (cations) or negatively charged (anions). The major electrolytes found in the body are sodium, potassium, calcium, magnesium, chloride, phosphate, sulphate and bicarbonate. The primary electrolytes of the ECF are sodium, chloride and bicarbonate and in the ICF are potassium and phosphates. Composition of major electrolytes in the body fluids (mOsm/Kg H20) Ions Plasma Interstitial ICF Fluid Sodium 146 142 14 Potassium 4.2 4.0 140 Chloride 105 108 4 Bicarbonate 27 28.3 10 Sodium It is the major cation of ECF. About 45% of sodium stored is found in ECF, 45% in the bone and the remaining intracellularly. It plays an important role in the excitability of muscles and neurons and in regulating the fluid balance in the body. A constant sodium equilibrium in maintained in the ECF by two mechanisms-long term and short-term control. The short-term control is achieved by the ADH- thirst control system whereas long term control is by both ingestion and urinary excretion of sodium. Short term Control (ADH-Thirst Control System) If ECF sodium rises, it stimulates the release of ECF and thirst. Water gained by this mechanism, dilutes the ECF thereby restoring normal sodium level. This increases the blood volume and a slight increase in BP, which in turn increases the GFR and excretion of excess sodium and water there by restoring the ECF volume to its normal level. Long-term Control (Salt hunger/ Sodium ingestion) A deficiency of sodium in the ECF causes increased excretion of water due to inhibition of the release of ADH. A decline in osmolality decreases the GFR with a subsequent increase in reabsorption of sodium and water. Many sodium deficient animals have a strong behavioral drive to salt to replace the deficiency of sodium. This is called as salt hunger and is commonly seen in ruminants. An increase in angiotensin II stimulates the salt hunger. A decrease in the plasma sodium and BP stimulates the release of aldosterone from the adrenal cortex via the Renin- Angiotensin system. Aldosterone enhances the reabsorption of sodium from the renal tubule. Aldosterone also increases the secretion of potassium ions from the renal tubules into the lumen. Urinary excretion of Sodium Sodium is filtered at the glomerulus and most of it is reabsorbed in the renal tubules. If the plasma sodium or the GFR increases, the amount of sodium filtered into the tubule will also increase but the reabsorption of sodium will not increase. An increase in the arterial BP results in the release of Atrial Natriuretic factor (ANF) from the atria of the heart. This hormone inhibits renin and aldosterone release which results in increased excretion of sodium and inhibition of reabsorption of sodium. Along with sodium, water will also be lost thereby bringing the BP back to normal level. Potassium It is the major cation of intra cellular fluid and about 89% of the total body content of potassium is present in the ICF. Potassium is important for the functioning of excitable cells and in the regulation of fluid levels within the cells. 30  Potassium output in usually equal to the potassium input. Almost nearly all the potassium filtered by the kidney glomeruli is reabsorbed by proximal convoluted tubule and is secreted in the distal tubule and the collecting ducts. Potassium reabsorption by the tubular cells occurs by active transport of potassium into the cells in exchange for sodium through the Na/K ATPase system. Potassium concentration is regulated by the aldosterone. An increase in ECF potassium results in the aldosterone release, which increases the potassium excretion in the urine and returning of the plasma potassium to its normal level. Potassium is secreted in exchange for the sodium ion in the tubular cells. Hydrogen ion secretion competes with K+ for Na+ with which it exchanges. Therefore, an increased H + secretion depresses K+ secretion. Likewise, an increased reabsorption of Na + facilitates increased K+ secretion. An excess of aldosterone results in hypokalemia whereas deficiency of aldosterone causes hyperkalemia. Chloride and bicarbonate The sodium ions are balanced electrically with the chloride and bicarbonate ions. The chloride ions are regulated secondarily to sodium and bicarbonate ions. The excretion or reabsorption of sodium ions is accompanied by chloride ions. Similarly, chloride ions are excreted along with the bicarbonate ions to maintain electroneutrality in the ECF. The bicarbonate ion is unique in that it is formed or removed rapidly by the body. Bicarbonates are formed and removed by carbon dioxide. EXCRETION IN BIRDS Urine formation in birds is almost similar to the mammals but still then there are some notable differences: Presence of two major types of nephrons which are functionally different. Presence of renal portal system. Formation of uric acid instead of urea as the end product of nitrogen metabolism. Post renal modification of the urine in the ureter. In the birds, the ureters transport the urine to the cloaca, which is the common collection site for digestive, reproductive and urinary organs. There is no urinary bladder in birds. NEPHRON TYPES Avian kidneys are characterized by having two major types of nephrons: Reptilian type; and Mammalian type The reptilian type nephrons are located in the cortex and it lacks the loop of Henle. It has no capacity to concentrate the urine, i.e., there is no tubular transport system and whatever solute and water is present in the filtrate, directly passes to the cloaca. Mammalian type of nephrons have well defined loop of Henle. It has the capacity to concentrate the urine. In this tubular transport system is present. RENAL PORTAL SYSTEM A unique feature of avian kidney is its Renal Portal System (RPS) which provides an extra branch of blood flow to the renal tubules along with peritubular capillaries. Venous blood from portal vein gives one branch to the kidney and this branch provides the microcapillaries which perfuse the tubules along with peritubular capillaries. Both the branches of capillaries are interconnected and drained by the venous system to the posterior vena cava. When it leaves these capillary networks and enters the renal vein there is a valve which regulates the transition of the blood in these capillary networks. URIC ACID FORMATION AND EXCRETION The metabolic end product of protein and amino acids in reptiles and birds is the uric acid (instead of urea in mammals). Uric acid is formed in liver and also in kidneys from ammonia. Uric acid is freely filterable at the glomerulus, and it is also secreted by the tubules. Tubule secretion accounts for 90% of total uric acid eliminated. 31  The renal portal system may provide a greater quantity of blood to the tubules for the secretion of uric acid by the tubules. Since greater quantity of uric acid is available in the tubules, which exceeds the solubility, the uric acid is precipitated. It passes through the tubules in the precipitated form and appears in the urine as a white coagulum. Since the uric acid is not in solution, it does not contribute to osmotic pressure, and thus avoids obligatory water loss. MODIFICATION OF THE URETERAL URINE The post renal modification of urine is possible in the birds when the urine reaches the cloaca water is drawn back to colon and cecum due to antiperistaltic movement of colon. So, when urine is exposed to colon and cecum for water absorption, sodium is also reabsorbed. CONCENTRATION OF AVIAN URINE Renal response to ADH in birds is similar to that of the mammals. In addition to the action of ADH on the tubular cells it also controls the functioning of reptilian and mammalian type of nephrons. URINE CHARACTERISTICS AND FLOW Birds urine when mixed with feces is cream colored and contains thick mucus. The precipitated uric acid is mixed with mucus and mucus facilitates the carrying of uric acid in the urine. Utilization of Learning Self-gauging assessment: 1. Discuss the uric acid formation and excretion in birds? 2. What are the notable differences of avian and mammalian urinary system? 3. Characterize the avian urine. 4. Differentiate the reptilian and mammalian type of nephron in birds. IMPLICATIONS: _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ 32  Learning Resource Materials MODULE 06: THE DIGESTIVE SYSTEM Target Outcomes At the end of the lesson, you are expected to: 1. Differentiate ruminant and monogastric gastrointestinal tract; 2. Identify factors of digestion; 3. Enumerate functions of saliva and its importance in the ruminant animals; 4. Understand the basic unit of salivary secretion; and 5. Explain the mechanism of salivary secretion, its control and importance in animals. Abstraction PHYSIOLOGY OF DIGESTION AND ABSORPTION Digestion is the process of breakdown of complex food into simpler form by the activities of the alimentary tract and glandular secretions for absorption of nutrients and the rejection of their residues. Food Food is a complex mixture of substances like carbohydrates proteins, fats, vitamins, inorganic salts and water to meet the nutri