Interview Handbook v1.0 PDF

1 Table of Contents Pg No. 1. Diges ve System …………………………………………………………………3 2. Respiratory System………………………………………………………………14 3. Circulatory System……………………………………………………………….23 4. Urinary System…………………………………………………………………….43 5. Nervous System…………………………………………………………………..55 6. Musculoskeletal System……………………………………………………….69 7. Endocrine System………………………………………………………………..79 2 The Diges ve System The process of diges on involves intake of the food (Inges on), breakdown of the food into micromolecules (Diges on), absorp on of these molecules into the blood stream (Absorp on), the absorbed substances becoming components of cells (Assimila on) and elimina on of the undigested substances (Eges on). Diges ve system includes the alimentary canal and associated diges ve glands. Structure of Alimentary Canal The alimentary canal is a con nuous, muscular diges ve tract that begins with an anterior opening, the mouth and opens out posteriorly through the anus. The alimentary canal consists of mouth, buccal cavity, pharynx, oesophagus, stomach, intes ne, rectum and anus. The mouth is concerned with the recep on of food and leads to the buccal cavity or oral cavity. Mechanical diges on is ini ated in the buccal cavity by chewing with the help of teeth and tongue. Chemical diges on is through salivary enzymes secreted by the salivary glands. 3 Human beings and many mammals form two sets of teeth during their life me, a set of 20 temporary milk teeth (deciduous teeth) which gets replaced by a set of 32 permanent teeth (adult teeth). This type of den on is called diphyodont. The permanent teeth are of four diﬀerent types (heterodont), namely, Incisors (I) chisel like cu ng teeth, Canines (C) dagger shaped tearing teeth, Pre molars (PM) for grinding, and Molars (M) for grinding and crushing. Arrangement of teeth in each half of the upper and lower jaw, in the order of I, C, PM and M. The hard chewing surface of the teeth is made of enamel and helps in mas ca on of food. Tongue is a freely movable muscular organ atached at the posterior end by the frenulum to the ﬂoor of the buccal cavity and is free in the front. The oral cavity leads into a short common passage for food and air called pharynx. The oesophagus and the trachea (windpipe) open into the pharynx. Food passes into the oesophagus through a wide opening called gullet at the back of the pharynx. A car laginous ﬂap called epiglo s prevents the entry of food into the glo s (opening of trachea) during swallowing. Two masses of lymphoid ssue called tonsils are also located at the sides of the pharynx. Oesophagus is a thin long muscular tube concerned with conduc on of the food to a ‘J’ shaped stomach passing through the neck, thorax and diaphragm. A cardiac sphincter (gastro oesphageal sphincter) regulates the opening of oesophagus into the stomach. If the cardiac sphincter does not contract properly during the churning ac on of the stomach the gastric juice with acid may ﬂow back into the oesophagus and cause heart burn, resul ng in GERD (Gastroesophageal Reﬂex Disease). The stomach func ons as the temporary storage organ for food and is located in the upper le por on of the abdominal cavity. The opening of the stomach into the duodenum is guarded by the pyloric sphincter. It periodically allows par ally digested food to enter the duodenum and prevents regurgita on of food. The inner wall of stomach has many folds called gastric rugae which unfolds to accommodate a large meal. The small intes ne assists in the ﬁnal diges on and absorp on of food. It is the longest part of the alimentary canal and has three regions, a ‘U’ shaped duodenum (25cm long), a long coiled middle por on jejunum (2.4m long) and a highly coiled ileum (3.5m long). Ileum is the longest part of the small intes ne and opens into the cecum of the large intes ne. 4 The ileal mucosa has numerous vascular projec ons called villi which are involved in the process of absorp on and the cells lining the villi produce numerous microscopic projec ons called microvilli giving a brush border appearance that increase the surface area enormously. The large intes ne consists of cecum, colon and rectum. The cecum is a small blind pouch like structure that opens into the colon and it possesses a narrow ﬁnger like tubular projec on called vermiform appendix. The colon is divided into four regions – an ascending, a transverse, a descending part and a sigmoid colon. The colon is lined by dila ons called haustra (singular – haustrum). The “S” shaped sigmoid colon (pelvic colon) opens into the rectum. Rectum is concerned with temporary storage of faeces. The rectum open out through the anus. The anus is guarded by two anal sphincter muscles. The anal mucosa is folded into several ver cal folds and contains arteries and veins called anal columns. Anal column may get enlarged and causes piles or haemorrhoids. 5 Diges ve Glands Diges ve glands are exocrine glands which secrete biological catalysts called enzymes. The diges ve glands associated with the alimentary canal are salivary glands, liver and pancreas. Stomach wall has gastric glands that secrete gastric juice and the intes nal mucosa secretes intes nal juice. Salivary Glands There are three pairs of salivary glands in the mouth. They are the largest paro ds gland in the cheeks, the sub-maxillary/sub-mandibular in the lower jaw and the sublingual beneath the tongue. Gastric Glands The wall of the stomach is lined by gastric glands. Chief cells or pep c cells or zymogen cells in the gastric glands secrete gastric enzymes and Goblet cells secrete mucus. Liver The liver, the largest gland in our body is situated in the upper right side of the abdominal cavity, just below the diaphragm. The liver consists of two major le and right lobes and two minor lobes. These lobes are connected with diaphragm. Each lobe has many hepa c lobules. Liver cells (hepa c cells) secrete bile which is stored and concentrated in a thin muscular sac called the gall bladder. The duct of gall bladder (cys c duct) along with the hepa c duct from the liver forms the common bile duct. The bile duct passes downwards and joins with the main pancrea c duct to form a common duct called hepato-pancrea c duct. The opening of the hepato-pancrea c duct into the duodenum is guarded by a sphincter called the sphincter of Oddi. Liver has high power of Cys c duct regenera on and liver cells are replaced by new ones every 3-4 weeks. 6 Apart from bile secre on, the liver also performs several func ons: 1. Destroys aging and defec ve blood cells. 2. Stores glucose in the form of glycogen or disperses glucose into the blood stream with the help of pancrea c hormones. 3. Stores fat soluble vitamins and iron. 4. Detoxiﬁes toxic substances. 5. Involves in the synthesis of non-essen al amino acids and urea. Pancreas The second largest gland in the diges ve system is the Pancreas, which is a yellow coloured, compound elongated organ consis ng of exocrine and endocrine cells. It is situated between the limbs of the ‘U’ shaped duodenum. The exocrine por on secretes pancrea c juice containing enzymes such as pancrea c amylase, trypsin and pancrea c lipase and the endocrine part called Islets of Langerhans, secretes hormones such as insulin and glucagon. The pancrea c duct directly opens into the duodenum. Diges on of Food and Role of Diges ve Enzymes The process of diges on converts the solid food into absorbable and assimilable forms. This is accomplished by mechanical and chemical processes. Diges on in the Buccal Cavity The smell, sight and taste as well as the mechanical s mula on of food in the mouth, triggers a reﬂex ac on which results in the secre on of saliva. The mechanical diges on starts in the mouth by grinding and chewing of food. It is called mas ca on. The mucus in saliva prepares the food for swallowing by moistening, so ening, lubrica ng and adhering the mas cated food into a bolus. The bolus is then passed into the pharynx and then into the oesophagus by swallowing or deglu on. The bolus further passes down through the oesophagus to the stomach by successive waves of muscular contrac on called peristalsis. The gastro oesophageal sphincter controls the passage of food into the stomach. 7 Diges on in the Stomach Food remains in the stomach for 4 to 5 hours, the rhythmic peristal c movement churns and mixes the food with gastric juice and make it into a creamy liquid called chyme. The gastric secre on is partly controlled by autonomic reﬂexes. The secre on of gastric juice begins when the food is in the mouth. The gastric juice contains HCl and proenzymes. The stomach prepares food for the small intes ne, where diges on and absorp on into the bloodstream take place. The stomach controls passage of foods into the ﬁrst part of the small intes ne so that it proceeds only when it is chemically ready and in small amounts. Diges on in the Small Intes ne The bile, pancrea c juice and intes nal juice are the secre ons released into the small intes ne. Movements generated by the muscularis layer of the small intes ne helps in the thorough mixing of the food with various secre ons in the intes ne and thereby facilitate diges on. The bile contains bile pigments (bilirubin and biliverdin) as the break down products of hemoglobin of dead RBCs, bile salts, cholesterol and phospholipids but has no enzymes. Bile helps in emulsiﬁca on of fats. Bile salts reduce the surface tension of fat droplets and break them into small globules. Bile also ac vates lipases to digest lipids Proteins and par ally digested proteins in the chyme on reaching the intes ne are acted upon by the proteoly c enzymes of pancrea c juice. The pancrea c juice contains enzymes such as trypsinogen, chymotrypsinogen, carboxypep dases, pancrea c amylases, pancrea c lipases and nucleases. Trypsinogen is ac vated by an enzyme, enterokinase, secreted by the intes nal mucosa into ac ve trypsin, which in turn ac vates the enzyme chymotrypsinogen in the pancrea c juice. Trypsin hydrolyses proteins into polypep des and peptones, while chymotrypsin hydrolyses pep de bonds associated with speciﬁc amino acids. The pancrea c amylase converts glycogen and starch into maltose. Lipase acts on emulsiﬁed fat (triglycerides) and hydrolyses them into free faty acid and monoglycerides. Monoglycerides are further hydrolysed to faty acid and glycerol. Nucleases in the pancrea c juice break the nucleic acid into nucleo des and nucleosides. The secre ons of the Brunner's gland along with the secre ons of the intes nal glands cons tute the intes nal juice or succus entericus. The enzymes in the intes nal juice such as maltase, lactase, sucrase (invertase), 8 pep dases, lipases, nucleo dases and nucleosidases act on the breakdown products of bile and pancrea c diges on. The mucus along with the bicarbonate ions from the pancreas provides an alkaline medium (pH 7.8) for the enzyma c ac on. As a result of diges on, all macromolecules of food are converted into their corresponding monomeric units. The simple substances thus formed are absorbed in the jejunum and ileum region of the small intes ne. The undigested and unabsorbed substances are propelled into the large intes ne. The ac vi es of the gastro-intes nal tract are carried out by the neural and hormonal control for proper coordina on of diﬀerent parts. Gastric and intes nal secre ons are s mulated by neural signals. Hormonal control of the secre on of diges ve juices is carried out by local hormones produced by the gastric and intes nal mucosa. 9 Absorp on and Assimila on of Proteins, Carbohydrates and Fats Absorp on is a process by which the end product of diges on passes through the intes nal mucosa into the blood and lymph. The villi in the lumen of ileum are the absorbing units, consis ng of a lacteal duct in the middle surrounded by ﬁne network of blood capillaries. The process of absorp on involves ac ve, passive and facilitated transport. Small amounts of glucose, amino acids and electrolytes like chloride ions are generally absorbed by simple diﬀusion. The passage of these substances into the blood depends upon concentra on gradients. However, some of the substances like fructose are absorbed with the help of the carrier ions like Na+. This mechanism is called facilitated transport. Nutrients like amino acids, glucose and electrolytes like Na+ are absorbed into the blood against the concentra on gradient by ac ve transport. The insoluble substances like faty acids, glycerol and fat soluble vitamins are ﬁrst incorporated into small, spherical water soluble droplets called micelles and are absorbed into the intes nal mucosa where they are re-synthesized into protein coated fat globules called chylomicrons which are then transported into the lacteals within the intes nal villi and eventually empty into lympha c duct. The lympha c ducts ul mately release the absorbed substances into the blood stream. While the faty acids are absorbed by the lymph duct, other materials are absorbed either ac vely or passively by the capillaries of the villi. Water soluble vitamins are absorbed by simple diﬀusion or ac ve transport. Transport of water depends upon the osmo c gradient. Absorp on of substances in the alimentary canal takes place in mouth, stomach, small intes ne and large intes ne. However maximum absorp on takes place in the small intes ne. Absorp on of simple sugars, alcohol and medicines takes place in the stomach. Certain drugs are absorbed by blood capillaries in the lower side of the tongue and mucosa of mouth. Large intes ne is also involved in absorp on of more amounts of water, vitamins, some minerals and certain drugs. Absorbed substances are transported through blood and lymph to the liver through the hepa c portal system. From the liver, nutrients are transported to all other regions of the body for u liza on. All the body ssues u lize the absorbed substance for their ac vi es and incorporate into their protoplasm, this process is called assimila on. 10 Eges on The diges ve waste and unabsorbed substances in the ileum enter the large intes ne and it mostly contains ﬁbre called roughage. The roughage is u lized by symbio c bacteria in the large intes ne to produce substances like vitamin K and other metabolites. All these substances are absorbed in the colon along with water. The waste is then solidiﬁed into faecal mater in the rectum. The faecal mater ini ates a neural reﬂex causing an urge or desire for its removal. The eges on of faeces through the anal opening is called defaeca on. It is a voluntary process and is carried out by a peristal c movement. Vocabulary 1. Absorp on - Passage of materials through the walls of the small intes ne into the bloodstream. 2. Amino acids - Small building blocks of proteins (like links in a chain), released when proteins are digested. 3. Amylase - Enzyme secreted by the pancreas to digest starch. 4. Anus - Terminal end or opening of the diges ve tract to the outside of the body. 5. Appendix - Blind pouch hanging from the cecum (in the right lower quadrant [RLQ]). 6. Bile - Diges ve juice made in the liver and stored in the gallbladder. 7. Bilirubin - Pigment released by the liver in bile. 8. Bowel - Intes ne. 9. Cecum - First part of the large intes ne. 10. Colon - Large intes ne, consis ng of the cecum; the ascending, transverse, and descending. segments of the colon; and the rectum. 11. Common bile duct - Carries bile from the liver and gallbladder to the duodenum. Also called the choledochus. 12. Defeca on - Elimina on of feces from the diges ve tract through the anus. 13. Deglu on - Swallowing. 14. Den n - The primary material found in teeth. It is covered by the enamel in the crown and a protec ve layer of cementum in the root. 15. Diges on - Breakdown of complex foods to simpler forms. 16. Duodenum - First part of the small intes ne. 11 17. Elimina on - Act of removal of indiges ble materials as feces. 18. Enamel - Hard, outermost layer of a tooth. 19. Esophagus - Tube connec ng the throat to the stomach. 20. Gallbladder - Small sac under the liver; stores bile. 21. Ileum - Third part of the small intes ne 22. Insulin - Hormone produced by the endocrine cells of the pancreas. It transports sugar from the blood into cells and s mulates glycogen forma on by the liver. 23. Jejunum - Second part of the small intes ne. 24. Liver - A large organ located in the RUQ of the abdomen. The liver secretes bile; stores sugar, iron, and vitamins; produces blood proteins; and destroys worn-out red blood cells. 25. Esophageal sphincter - Ring of muscles between the esophagus and the stomach. Also called cardiac sphincter. 26. Mas ca on - Chewing. 27. Palate - Roof of the mouth. 28. Pancreas - Organ under the stomach; produces insulin (for transport of sugar into cells) and enzymes. 29. Papillae - (singular: papilla) Small eleva ons on the tongue. 30. Peristalsis - Rhythmic contrac ons of the tubular organs. 31. Pharynx - Throat 32. Pylorus - Distal region of the stomach, opening to the duodenum. 33. Rectum - Last sec on of the large intes ne, connec ng the end of the colon and the anus. 34. Saliva - Diges ve juice produced by salivary glands. 35. Salivary glands - Paro d, sublingual, and submandibular glands. 36. Sigmoid colon - Fourth and last, S-shaped segment of the colon, just before the rectum; emp es into the rectum. 37. Sphincter - Circular ring of muscle that constricts a passage or closes a natural opening. 38. Stomach - Muscular organ that receives food from the esophagus. 39. Uvula - So ssue hanging from the middle of the so palate. 40. Villi (singular: villus) - Microscopic projec ons in the wall of the small intes ne that absorb nutrients into the bloodstream. 41. Anorexia - Lack of appe te. Anorexia 42. Ascites - Abnormal accumula on of ﬂuid in the abdomen. 12 43. Cons pa on - Diﬃculty in passing stools (feces). Laxa ves and cathar cs are medica ons to promote movement of stools. 44. Diarrhea - Frequent passage of loose, watery stools. 45. Dysphagia- Diﬃculty in swallowing. 46. Eructa on- Gas expelled from the stomach through the mouth. 47. Flatus- Gas expelled through the anus. 48. Hematochezia -Passage of fresh, bright red blood from the rectum. 49. Jaundice (icterus) - Yellow-orange colora on of the skin and whites of the eyes caused by high levels of bilirubin in the blood (hyperbilirubinemia). 50. Melena - Black, tarry stools; feces containing digested blood. 51. Nausea - Unpleasant sensa on in the stomach associated with a tendency to vomit. 52. Steatorrhea - Fat in the feces; frothy, foul-smelling fecal mater. 53. Gastroesophageal reﬂux disease (GERD) - Solids and ﬂuids return to the mouth from the stomach. Heartburn. 54. Hernia - Protrusion of an organ or part through the muscle normally containing it. 55. Cirrhosis - Chronic degenera ve disease of the liver. 56. Pancrea s - Inﬂamma on of the pancreas. 57. Viral Hepa s - Inﬂamma on of the liver caused by a virus. 13 Respiratory System The respiratory system includes external nostrils, nasal cavity, pharynx, larynx, trachea, bronchi and bronchioles and lungs which contain alveoli. The parts star ng from the external nostrils up to the terminal bronchioles cons tute the conduc ng zone, whereas the alveoli and the ducts are called the respiratory zone. The parts of the conduc ng zone, humidiﬁes and warms the incoming air. In human beings, air enters the upper respiratory tract through the external nostrils. The air passing through the nostrils is ﬁltered by ﬁne hairs and mucus lining the passage. The external nostrils lead to the nasal chamber which opens into the nasopharynx which opens through the glo s of the larynx region into the trachea. The ciliated epithelial cells lining the trachea, bronchi and bronchioles secrete mucus. Mucus membrane lining the airway contains goblet cells which secrete mucus, a slimy material rich in glycoprotein. Microorganisms and dust par cles atach in the mucus ﬁlms and are carried upwards to pass down the gullet during normal swallowing. During swallowing a thin elas c ﬂap called epiglo s prevents the food from entering the larynx and avoids choking of food. The trachea is semiﬂexible tube supported by mul ple car laginous rings which extends up to the midthoracic cavity and at the level of the 5th thoracic vertebra where it divides into right and le primary bronchi, one bronchus to each lung. Within the lungs the bronchi divide repeatedly into secondary and ter ary bronchi and further divides into terminal bronchioles and respiratory bronchioles. Bronchi have ‘C’ shaped curved car lage plates to ensure that the air passage does not collapse or burst as the air pressure changes during breathing. The bronchioles are without car laginous rings and have rigidity that prevent them from collapsing but are surrounded by smooth muscle which contracts or relaxes to adjust the diameter of these airways. The ﬁne respiratory bronchioles terminate into highly vascularised thin-walled pouch like air sacs called alveoli meant for gaseous exchange. 14 The lungs are light spongy ssues enclosed in the thoracic cavity surrounded by an air ght space. The thoracic cavity is bound dorsally by the vertebral column and ventrally by the sternum, laterally by the ribs and on the lower side by the dome shaped diaphragm. The lungs are covered by double walled pleural membrane containing a several layers of elas c connec ve ssues and capillaries, which encloses the pleural ﬂuid. Pleural ﬂuid reduces fric on when the lungs expand and contract. Respiratory Func ons The ﬁve primary func ons of the respiratory system are: 1. To exchange O2 and CO2 between the atmosphere and the blood. 2. To maintain homeosta c regula on of body pH. 3. To protect us from inhaled pathogens and pollutants. 4. To maintain the vocal cords for normal communica on (vocaliza on). 5. To remove the heat produced during cellular respira on. 15 Mechanism of breathing The movement of air between the atmosphere and the lungs is known as ven la on or breathing. Inspira on and expira on are the two phases of breathing. Inspira on is the movement of atmospheric air into the lungs and expira on is the movement of alveolar air that diﬀuse out of the lungs. Lungs do not contain muscle ﬁbres but expands and contracts by the movement of the ribs and diaphragm. The diaphragm is a sheet of ssue which separates the thorax from the abdomen. In a relaxed state, the diaphragm is domed shaped. Ribs are moved by the intercostal muscles. External and internal intercostal muscles found between the ribs and the diaphragm helps in crea ng pressure gradients. Inspira on occurs if the pressure inside the lungs (intrapulmonary pressure) is less than the atmospheric pressure likewise expira on takes place when the pressure within the lungs is higher than the atmospheric pressure. 16 Inspiraton is ini ated by the contrac on of the diaphragm muscles and external intercostal muscles, which pulls the ribs and sternum upwards and outwards and increases the volume of the thoracic chamber in the dorso–ventral axis, forcing the lungs to expand the pulmonary volume. The increase in pulmonary volume and decrease in the intrapulmonary pressure forces the fresh air from outside to enter the air passages into the lungs to equalize the pressure. This process is called inspira on. Relaxa on of the diaphragm allows the diaphragm and sternum to return to its dome shape and the internal intercostal muscles contract, pulling the ribs downward reducing the thoracic volume and pulmonary volume. This results in an increase in the intrapulmonary pressure slightly above the atmospheric pressure causing the expulsion of air from the lungs. This process is called expira on. On an average, a healthy human breathes 12–16 mes/minute. An instrument called Spirometer is used to measure the volume of air involved in breathing movements for clinical assessment of a person’s pulmonary func on. Respiratory Volumes and Capaci es The volume of air present in various phases of respira on is denoted as respiratory volumes. Respiratory Volumes: Tidal Volume (TV) Tidal volume is the amount of air inspired or expired with each normal breath. It is approximately 500 mL., i.e. a normal human adult can inspire or expire approximately 6000 to 8000mL of air per minute. During vigorous exercise, the dal volume is about 4–10 mes higher. Inspiratory Reserve volume (IRV) Addi onal volume of air a person can inspire by forceful inspira on is called Inspiratory Reserve Volume. The normal value is 2500–3000 mL. Expiratory Reserve volume (ERV) Addi onal volume of air a person can forcefully exhale by forceful expira on is called Expiratory Reserve Volume. The normal value is 1000–1100 mL. Residual Volume (RV) The volume of air remaining in the lungs a er a forceful expira on. It is approximately 1100–1200 mL. 17 Respiratory Capaci es: Vital capacity (VC) the maximum volume of air that can be moved out during a single breath following a maximal inspira on. A person ﬁrst inspires maximally then expires maximally. VC = ERV+TV+IRV Inspiratory capacity (IC) The total volume of air a person can inhale a er normal expira on. It includes dal volume and inspiratory reserve volume. IC = TV+IRV Expiratory capacity (EC) The total volume of air a person can exhale a er normal inspira on. It includes dal volume and expiratory reserve volume. EC=TV+ERV Total Lung Capacity (TLC) The total volume of air which the lungs can accommodate a er forced inspira on is called Total Lung Capacity. This includes the vital capacity and the residual volume. It is approximately 6000mL. TLC=VC+RV Minute Respiratory Volume The amount of air that moves into the respiratory passage per minute is called minute respiratory volume. Normal TV = 500mL; Normal respiratory rate = 12 mes/minute. Therefore, minute respiratory volume = 6 Litres/minute (for a normal healthy man). Lung Volumes and Capacity 18 Respiratory Pigments Hemoglobin Hemoglobin belongs to the class of conjugated protein. The iron containing pigment por on haem cons tutes only 4% and the rest colourless protein globin belongs to histone class. Hemoglobin has a molecular weight of 68,000 daltons and contains four atoms of iron, each of which can combine with a molecule of oxygen. Methemoglobin If the iron component of the haem is in the ferric state, than the normal ferrous state, it is called methemoglobin. Methemoglobin does not bind with O Normally RBC contains less than 1% methemoglobin. 19 Vocabulary 1. Alveolus (plural:alveoli) - Air sac in the lung. 2. Apex of the lung - Tip or uppermost por on of the lung. An apex is the p of a structure. 3. Base of the Lung - Lower por on of the lung; from the Greek basis, founda on. 4. Bronchioles - Smallest branches of the bronchi. Terminal bronchioles lead to alveolar ducts. 5. Bronchus (plural:bronchi) - Branch of the trachea (windpipe) that is a passageway into the lung; bronchial tube. 6. Cilia - Thin hairs atached to the mucous membrane epithelium lining the respiratory tract. 7. Diaphragm - Muscle separa ng the chest and abdomen. It contracts and relaxes to make breathing possible. 8. Epiglo s - Lid-like piece of car lage that covers the larynx, preven ng food from entering the larynx and trachea during swallowing. 9. Expira on - Breathing out (exhala on). 10. Glo s - Slit-like opening to the larynx. 11. Hilum (of lung) Midline region where the bronchi, blood vessels, and nerves enter and exit the lungs. 12. Inspira on - Breathing in (inhala on). 13. Larynx - Voice box; containing the vocal cords. 14. Lobe - Division of a lung. 15. Medias num Region between the lungs in the chest cavity. It contains the trachea, heart, aorta, esophagus, and bronchial tubes. 16. Nares - Openings through the nose carrying air into the nasal cavi es. 17. Pala ne - tonsil One of a pair of almond-shaped masses of lympha c ssue in the oropharynx 18. Paranasal - sinus One of the air cavi es in the bones near the nose. 19. Parietal - pleura Outer fold of pleura lying closer to the ribs and chest wall. 20. Pharynx - Throat; including the nasopharynx, oropharynx, and laryngopharynx. 21. Pleura - Double-folded membrane surrounding each lung. 22. Pleural - cavity Space between the folds of the pleura. 23. Pulmonary parenchyma - Essen al parts of the lung, responsible for respira on; bronchioles and alveoli. 24. Respira on - Process of moving air into and out of the lungs; breathing. 20 25. Trachea - Windpipe. 26. Visceral pleura - Inner fold of pleura lying closer to the lung ssue. 27. Ausculta on - Listening to sounds within the body. 28. Percussion - Tapping on a surface to determine the diﬀerence in the density of the underlying structure. 29. Rales (crackles) - Fine crackling sounds heard on ausculta on (during inhala on) when there is ﬂuid in the alveoli. 30. Rhonchi - Loud rumbling sounds heard on ausculta on of bronchi obstructed by sputum. 31. Sputum - Material expelled from the bronchi, lungs, or upper respiratory tract by spi ng. 32. Stridor - Strained, high-pitched sound heard on inspira on caused by obstruc on in the pharynx or larynx. 33. Wheezes - Con nuous high-pitched whistling sounds produced during breathing. 34. Croup - Acute viral infec on of infants and children with obstruc on of the larynx, barking cough, and stridor. 35. Diphtheria - Acute infec on of the throat and upper respiratory tract caused by the diphtheria bacterium (Corynebacterium). 36. Epistaxis - Nosebleed. 37. Pertussis - Whooping cough; highly contagious bacterial infec on of the pharynx, larynx, and trachea caused by Bordetella pertussis. 38. Bronchi s - Inﬂamma on of the bronchus. 39. Asthma - Chronic bronchial inﬂammatory disorder with airway obstruc on due to bronchial edema and constric on and increased mucus produc on. 40. Emphysema - is chronic breathlessness caused by gradual breakdown of the thin walls of the alveoli decreasing the total surface area of a gaseous exchange. i.e., widening of the alveoli is called emphysema. 41. Bronchiectasis - Chronic dila on of a bronchus secondary to infec on. 42. Chronic bronchi s - Inﬂamma on of bronchi persis ng over a long me; type of chronic obstruc ve pulmonary disease (COPD). 43. Cys c ﬁbrosis (CF) - Inherited disorder of exocrine glands resul ng in thick mucus secre ons in the respiratory tract that do not drain normally. 44. Atelectasis - Collapsed lung; incomplete expansion of alveoli. 45. Emphysema - Hyperinﬂa on of air sacs with destruc on of alveolar walls 21 46. Pneumoconiosis - Abnormal condi on caused by dust in the lungs, with chronic inﬂamma on, infec on, and bronchi s. 47. Pneumonia - Acute inﬂamma on and infec on of alveoli, which ﬁll with pus or products of the inﬂammatory reac on. 48. Pulmonary embolism (PE) - Clot or other material lodges in vessels of the lung. 49. Pulmonary ﬁbrosis - Forma on of scar ssue in the connec ve ssue of the lungs. 50. Sarcoidosis - Chronic inﬂammatory disease in which small nodules (granulomas) develop in lungs, lymph nodes, and other organs. 51. Tuberculosis (TB) - Infec ous disease caused by Mycobacterium tuberculosis; lungs usually are involved, but any organ in the body may be aﬀected. 52. Pleural eﬀusion - Abnormal accumula on of ﬂuid in the pleural space (cavity). 53. Pleurisy (pleuri s) - Inﬂamma on of the pleura. 54. Pneumothorax Collec on of air in the pleural space. 55. Chronic obstruc ve pulmonary disease (COPD) - Chronic condi on of persistent obstruc on of air ﬂow through bronchial tubes and lungs. COPD is caused by smoking, air pollu on, chronic infec on, and, in a minority of cases, asthma. Pa ents with predominant chronic bronchi s COPD are referred to as “blue bloaters” (cyano c, stocky build), whereas those with predominant emphysema are called “pink puﬀers” (short of breath, but with near- normal blood oxygen levels, and no change in skin color). 56. Cor pulmonale - Failure of the right side of the heart to pump a suﬃcient amount of blood to the lungs because of underlying lung disease. 57. Pulmonary func on tests (PFTs) - Tests that measure the ven la on mechanics of the lungs (airway func on, lung volume, and capacity of the lungs to exchange oxygen and carbon dioxide eﬃciently). 22 Circulatory System Body ﬂuids The body ﬂuid consists of water and substances dissolved in them. There are two types of body ﬂuids, the intracellular ﬂuid present inside the cells and the extracellular ﬂuid present outside the cells. The three types of extracellular ﬂuids are the inters al ﬂuid or ssue ﬂuid (surrounds the cell), the plasma (ﬂuid component of the blood) and lymph. The blood ﬂowing into the capillary from an arteriole has a high hydrosta c pressure. This pressure is brought about by the pumping ac on of the blood and it tends to force water and small molecules out through the permeable walls of the capillary into the ssue ﬂuid. The volume of ﬂuid which leaves the capillary to form ssue ﬂuid is the result of two pressure (hydrosta c pressure and Onco c pressure). At the anterior end of the capillary bed, the water poten al is lesser than hydrosta c pressure inside the capillary bed which is enough to push ﬂuid into the ssues. The ssue ﬂuid has low concentra on of protein than that of plasma. At the venous end of the capillary bed, the water poten al is greater than the hydrosta c pressure and the ﬂuid from the ssues ﬂows into the capillary and water is drawn back into the blood, taking with it waste products produced by the cells. Composi on of Blood Blood is the most common body ﬂuid that transports substances from one part of the body to the other. Blood is a connec ve ssue consis ng of plasma (ﬂuid matrix) and formed elements. The plasma cons tutes 55% of the total blood volume. The remaining 45% is the formed elements that consist of blood cells. The average blood volume is about 5000ml (5L) in an adult weighing 70 Kg. Plasma Plasma mainly consists of water (80-92%) in which the plasma proteins, inorganic cons tuents (0.9%), organic cons tuents (0.1%) and respiratory gases are dissolved. The four main types of plasma proteins synthesized in the liver are albumin, globulin, prothrombin and ﬁbrinogen. Albumin maintains the osmo c pressure of the blood. Globulin facilitates the transport of ions, hormones, lipids and assists in immune func on. Both Prothrombin and Fibrinogen are involved in blood clo ng. Organic cons tuents include urea, amino acids, glucose, fats and vitamins and the inorganic cons tuents include chlorides, carbonates and phosphates of potassium, sodium, calcium and 23 magnesium. The composi on of plasma is not always constant. Immediately a er a meal, the blood in the hepa c portal vein has a very high concentra on of glucose as it is transpor ng glucose from the intes ne to the liver where it is stored. The concentra on of the glucose in the blood gradually falls a er some me as most of the glucose is absorbed. If too much of protein is consumed, the body cannot store the excess amino acids formed from the diges on of proteins. The liver breaks down the excess amino acids and produces urea. Blood in the hepa c vein has a high concentra on of urea than the blood in other vessels namely, hepa c portal vein and hepa c artery. Liver receives its blood supply from two sources: the hepa c artery brings oxygenated blood from the heart, while the hepa c portal vein brings blood from the intes ne and other abdominal organs. The blood is re-turned from the liver to the heart by the hepa c veins. Red Blood Cells Red blood cells are abundant than the other blood cells. There are about 5 million to 5.5 millions of RBC mm23 of blood in a healthy man and 4.5-5.0 millions of RBC mm23 in healthy women. The RBCs are very small with the diameter of about 7µm (micrometer). The structure of RBC is shown in. The red colour of the RBC is due to the presence of a respiratory pigment, haemoglobin dissolved in the cytoplasm. Haemoglobin plays an important role in the transport of respiratory gases and facilitates the exchange of gases with the ﬂuid outside the cell ( ssue ﬂuid). The biconcave shaped RBCs increases the surface area to volume ra o; hence oxygen diﬀuses quickly in and out of the cell. The RBCs are devoid of nucleus, mitochondria, ribosomes and endoplasmic re culum. The absence of these organelles accommodates more hemoglobin thereby maximising the oxygen carrying capacity of the cell. The average life span of RBCs in a healthy individual is about 120 days a er which they are destroyed in the spleen (graveyard / cemetery of RBCs) and the iron component returns to the bone marrow for reuse. Erythropoie n is a hormone secreted by the kidneys in response to low oxygen and helps in diﬀeren a on of stem cells of the bone marrow to erythrocytes (erythropoiesis) in adults. The ra o of red blood cells to blood plasma is expressed as Haematocrit (packed cell volume). 24 White Blood Cells White blood cells (leucocytes) are colourless, amoeboid, nucleated cells devoid of haemoglobin and other pigments. Approximately 6000 to 8000 per cubic mm of WBCs are seen in the blood of an average healthy individual. The diﬀerent types of WBCs. Depending on the presence or absence of granules, WBCs are divided into two types, granulocytes and agranulocytes. Granulocytes Granulocytes are characterised by the presence of granules in the cytoplasm and are diﬀeren ated in the bone marrow. The granulocytes include neutrophils, eosinophils and basophils. (i) Neutrophils are also called heterophils or polymorphonuclear (cells with 3-4 lobes of nucleus connected with delicate threads) cells which cons tute about 60%- 65% of the total WBCs. They are phagocy c in nature and appear in large numbers in and around the infected ssues. (ii) Eosinophils have dis nctly bilobed nucleus and the lobes are joined by thin strands. They are non- phagocy c and cons tute about 2-3% of the total WBCs. Eosinophils increase during certain types of parasi c infec ons and allergic reac ons. (iii) Basophils are less numerous than any other type of WBCs cons tu ng 0.5%- 1.0% of the total number of leucocytes. The cytoplasmic granules are large sized, but fewer than eosinophils. Nucleus is large sized and constricted into several lobes but not joined by delicate threads. Basophils secrete substances such as heparin, serotonin and histamines. They are also involved in inﬂammatory reac ons. 25 Agranulocytes Agranulocytes are characterised by the absence of granules in the cytoplasm and are diﬀeren ated in the lymph glands and spleen. These are of two types, lymphocytes and monocytes. (i) Lymphocytes cons tute 28% of WBCs. These have large round nucleus and small amount of cytoplasm. The two types of lymphocytes are B and T cells. Both B and T cells are responsible for the immune responses of the body. B cells produce an bodies to neutralize the harmful eﬀects of foreign substances and T cells are involved in cell mediated immunity. (ii) Monocytes (Macrophages) are phagocy c cells that are similar to mast cells and have kidney shaped nucleus. They cons tute 1-3% of the total WBCs. The macrophages of the central nervous system are the ‘microglia’, in the sinusoids of the liver they are called ‘Kupﬀer cells’ and in the pulmonary region they are the ‘alveolar macrophages. Platelets Platelets are also called thrombocytes that are produced from megakaryocytes (special cells in bone marrow) and lack nuclei. Blood normally contains 1, 50,000 -3, 50,000 platelets mm23 of blood. They secrete substances involved in coagula on or clo ng of blood. The reduc on in platelet number can lead to clo ng disorders that result in excessive loss of blood from the body. ABO Blood Grouping Depending on the presence or absence of surface an gens on the RBCs, blood group in individual belongs to four diﬀerent types namely, A, B, AB and O. The plasma of A, B and O, individuals have natural an bodies (agglu nins) in them. Surface an gens are called agglu nogens. The an bodies (agglu nin) ac ng on agglu nogen A is called an A and the agglu nin ac ng on agglu nogen B is called an B. Agglu nogens are absent in O blood group. Agglu nogens A and B are present in AB blood group and do not contain an A and an B in them. Distribu on of an gens and an bodies in blood groups are shown in A, B and O are major allelic genes in ABO systems. All 26 agglu nogens contain sucrose, D-galactose, N-acetyl glucosamine and 11 terminal amino acids. The atachments of the terminal amino acids are dependent on the gene products of A and B. The reac on is catalysed by glycosyl transferase. Rh factor is a protein (D an gen) present on the surface of the red blood cells in majority (80%) of humans. This protein is similar to the protein present in Rhesus monkey, hence the term Rh. Individuals who carry the an gen D on the surface of the red blood cells are Rh1 (Rh posi ve) and the individuals who do not carry an gen D, are Rh2 (Rh nega ve). Rh factor compa bility is also checked before blood transfusion. When a pregnant woman is Rh2 and the foetus is Rh1 incompa bility (mismatch) is observed. During the ﬁrst pregnancy, the Rh2 an gens of the foetus does not get exposed to the mother’s blood as their blood are separated by placenta. However, small amount of the foetal an gen becomes exposed to the mother’s blood during the birth of the ﬁrst child. The mother’s blood starts to synthesize D an bodies. But during subsequent pregnancies the Rh an bodies from the mother (Rh2) enters the foetal circula on and destroys the foetal RBCs. This becomes fatal to the foetus because the child suﬀers from anaemia and jaundice. This condi on is called erythroblastosis fetalis. This condi on can be avoided by administra on of an D an bodies (Rhocum) to the mother immediately a er the ﬁrst childbirth. Coagula on of blood Blood clots or coagulates in response to trauma. The mechanism by which excessive blood loss is prevented by the forma on of clot is called blood coagula on or clo ng of blood. The clo ng process begins when the endothelium of the blood vessel is damaged and the connec ve ssue in its wall is exposed to the blood. Platelets adhere to collagen ﬁbres in the connec ve ssue and release substances that form the platelet plug which provides emergency protec on against blood loss. Clo ng factors released from the clumped platelets or damaged cells mix with clo ng factors in the plasma. The protein called prothrombin is converted to its ac ve form called thrombin in the presence of calcium and vitamin K. Thrombin helps in the conversion of ﬁbrinogen to ﬁbrin threads. The threads of ﬁbrins become interlinked into a patch that traps blood cell and seals the injured vessel un l the wound is healed. A er some me ﬁbrin ﬁbrils contract, squeezing out a straw- coloured ﬂuid through a meshwork called serum (Plasma without ﬁbrinogen is called serum). Heparin is an an coagulant produced in small quan es by mast cells of connec ve ssue which prevents coagula on in small blood vessels. 27 Composi on of Lymph and its Func ons About 90% of ﬂuid that leaks from capillaries eventually seeps back into the capillaries and the remaining 10% is collected and returned to blood system by means of a series of tubules known as lymph vessels or lympha cs. The ﬂuid inside the lympha cs is called lymph. The lympha c system consists of a complex network of thin-walled ducts (lympha c vessels), ﬁltering bodies (lymph nodes) and many lymphocy c cell concentra ons in various lymphoid organs. The lympha c vessels have smooth walls that run parallel to the blood vessels, in the skin, along the respiratory and diges ve tracts. These vessels serve as return ducts for the ﬂuids that are con nually diﬀusing out of the blood capillaries into the body ssues. Lymph ﬂuid must pass through the lymph nodes before it is returned to the blood. The lymph nodes that ﬁlter the ﬂuid from the lympha c vessels of the skin are highly concentrated in the neck, inguinal, axillaries, respiratory and diges ve tracts. The lymph ﬂuid ﬂowing out of the lymph nodes ﬂow into large collec ng duct which ﬁnally drains into larger veins that runs beneath the collar bone, the subclavian vein and is 28 emp ed into the blood stream. The narrow passages in the lymph nodes are the sinusoids that are lined with macrophages. The lymph nodes successfully prevent the invading microorganisms from reaching the blood stream. Cells found in the lympha cs are the lymphocytes. Lymphocytes collected in the lympha c ﬂuid are carried via the arterial blood and are recycled back to the lymph. Fats are absorbed through lymph in the lacteals present in the villi of the intes nal wall. Blood vessels – Arteries, Veins and Capillaries The vessels carrying the blood are of three types; they are the arteries, veins and capillaries. These vessels are hollow structures and have complex walls surrounding the lumen. The blood vessels in humans are composed of three layers, tunica in ma, tunica media and tunica externa. The inner layer, tunica in ma or tunica interna supports the vascular endothelium, the middle layer, tunica media is composed of smooth muscles and an extra cellular matrix which contains a protein, elas n. The contrac on and relaxa on of the smooth muscles results in vasoconstric on and vasodila on. The outer layer, tunica externa or tunica adven a is composed of collagen ﬁbres. Arteries The blood vessels that carry blood away from the heart are called arteries. The arteries usually lie deep inside the body. The walls of the arteries are thick, non- collapsible to withstand high pressure. Valves are absent and have a narrow lumen. All arteries carry oxygenated blood, except the pulmonary artery. The largest artery, the aorta (2.5 cm in diameter and 2 mm thick) branch into smaller arteries and culminates into the ssues as feed arteries. In the ssues the arteries branches into arterioles. As blood enters an arteriole it may have a pressure of 85 mm Hg (11.3 KPa) but as it leaves and ﬂows into the capillary, the pressure drops to 35 mm Hg (4.7 KPa). (Note 1 mm Hg =0.13 KPa. SI unit of mm Hg is Kilo Pascal (KPa)). Arterioles are small, narrow, and thin walled which are connected to the capillaries. A small sphincter lies at the junc on between the arterioles and capillaries to regulate the blood supply. Arteries do not always branch into arterioles, they can also form 29 anastomoses. Anastomoses are connec ons of one blood vessel (arteries) with another blood vessel. They provide alternate route of blood ﬂow if the original blood vessel is blocked. For e.g., Arteries in the joints contain numerous anastomoses. This allows blood to ﬂow freely even if one of the arteries closes during bending of the joints. Capillaries Capillary beds are made up of ﬁne networks of capillaries. The capillaries are thin walled and consist of single layer of squamous epithelium. Tunica media and elas n ﬁbres are absent. The capillary beds are the site for exchange of materials between blood and ssues. The walls of the capillaries are guarded by semilunar valves. The blood volume in the capillaries is high but the ﬂow of blood is slow. Mixed blood (oxygenated and deoxygenated) is present in the capillaries. The capillary bed may be ﬂooded with blood or may be completely bypassed depending on the body condi ons in a par cular organ. Veins Veins have thinner walls and a larger lumen and hence can be easily stretched. They carry deoxygenated blood except, the pulmonary vein. The blood pressure is low and the lumen has a wide wall which is collapsible. Tunica media is thinner in veins than in arteries. Unidirec onal ﬂow of blood in veins is due to the presence of semilunar valves that prevents backﬂow of blood. Blood samples are usually taken from the veins rather than artery because of low pressure in the veins. 30 Coronary Blood Vessels Blood vessels that supply blood to the cardiac muscles with all nutrients and removes wastes are the coronary arteries and veins. Heart muscle is supplied by two arteries namely right and le coronary arteries. These arteries are the ﬁrst branch of the aorta. Arteries usually surround the heart in the manner of a crown, hence called coronary artery (L. Corona - crown). Right ventricle and posterior por on of le ventricle are supplied by the right coronary artery. Anterior and lateral part of the le ventricle is supplied by the le coronary arteries. Heart The structure of the heart was described by Raymond de viessens, in 1706. Human heart is made of special type of muscle called the cardiac muscle. It is situated in the thoracic cavity and its apex por on is slightly lted towards le. It weighs about 300g in an adult. The size of our heart is roughly equal to a closed ﬁst. Heart is divided into four chambers, upper two small auricles or atrium and lower two large ventricles. The walls of the ventricles are thicker than the auricles due to the presence of papillary muscles. The heart wall is made up of three layers, the outer epicardium, middle myocardium and inner endocardium. The space present between the membranes is called pericardial space and is ﬁlled with pericardial ﬂuid. The two auricles are separated by inter auricular septum and the two ventricles are separated by inter ventricular septum The separa on of chambers avoids mixing of oxygenated and deoxygenated blood. The auricle communicates with the ventricle through an opening called auriculo ventricular aperture which is guarded by the auriculo ventricular valves. The opening between the right atrium and the right ventricle is guarded by the tricuspid valve (three ﬂaps or cusps), whereas a bicuspid (two ﬂaps or cusps) or mitral valve guards the opening between the le atrium and le ventricle. The valves of the heart allows the blood to ﬂow only in one direc on, i.e., from the atria to the 31 ventricles and from the ventricles to the pulmonary artery or the aorta. These valves prevent backward ﬂow of blood. The opening of right and le ventricles into the pulmonary artery and aorta are guarded by aor c and pulmonary valves and are called semilunar valves. Origin and Conduc on of Heartbeat The heart in human is myogenic (cardiomyocytes can produce spontaneous rhythmic depolarisa on that ini ates contrac ons). The cardiac cells with fastest rhythm are called the Pacemaker cells since they determine the contrac on rate of the en re heart. These cells are located in the right sinoatrial (SA) node/ Pacemaker. On the le side of the right atrium is a node called atrioventricular node (AV node). Two special cardiac muscle ﬁbres originate from the atrioventricular node and are called the bundle of His which runs down into the interventricular septum and the ﬁbres spread into the ventricles. These ﬁbres are called the Purkinje ﬁbres. Pacemaker cells produce excita on through depolarisa on of their cell membrane. Early depolarisa on is slow and takes place by sodium inﬂux and reduc on in potassium eﬄux. Minimum poten al is required to ac vate voltage gated calcium (Ca+) channels that causes rapid depolarisa on which results in ac on poten al. The pacemaker cells repolarise slowly via K1 eﬄux. Heartbeat Rhythmic contrac on and expansion of heart is called heartbeat. The contrac on of the heart is called systole, and the relaxa on of the heart is called diastole. The heart normally beats 70-72 mes per min in a human adult. During each cardiac cycle two sounds are produced that can be heard through a stethoscope. The ﬁrst heart sound (lub) is associated with the closure of the tricuspid and bicuspid valves whereas second heart sound (dub) is associated with the closure of the semilunar valves. These sounds are of clinical diagnos c signiﬁcance. An increased heart rate is called tachycardia and decreased heart rate is called bradycardia. 32 Cardiac Cycle The events that occur at the beginning of heartbeat and lasts un l the beginning of next beat is called cardiac cycle. It lasts for 0.8 seconds. The series of events that takes place in a cardiac cycle. PHASE 1: Ventricular Diastole- The pressure in the auricles increases than that of the ventricular pressure. AV valves are open while the semi lunar valves are closed. Blood ﬂows from the auricles into the ventricles passively. PHASE 2: Atrial Systole - The atria contracts while the ventricles are s ll relaxed. The contrac on of the auricles pushes maximum volume of blood to the ventricles un l they reach the end diastolic volume (EDV). EDV is related to the length of the cardiac muscle ﬁbre. More the muscle is stretched, greater the EDV and the stroke volume. PHASE 3: Ventricular Systole (isovolumetric contrac on) - The ventricular contrac on forces the AV valves to close and increases the pressure inside the ventricles. The blood is then pumped from the ventricles into the aorta without change in the size of the muscle ﬁbre length and ventricular chamber volume (isovolumetric contrac on). PHASE 4: Ventricular Systole (ventricular ejec on) - Increased ventricular pressure forces the semilunar valves to open and blood is ejected out of the ventricles without backﬂow of blood. This point is the end of systolic volume (ESV). PHASE 5: (Ventricular Diastole) -The ventricles begins to relax, pressure in the arteries exceeds ventricular pressure, resul ng in the closure of the semilunar valves. The heart returns to phase 1 of the cardiac cycle. Cardiac Output The amount of blood pumped out by each ventricle per minute is called cardiac output(CO). It is a product of heart rate (HR) and stroke volume (SV). Heart rate or pulse is the number of beats per minute. Pulse pressure = systolic pressure – diastolic pressure. Stroke volume (SV) is the volume of blood pumped out by one ventricle with each beat. SV depends on ventricular contrac on. CO = HR X SV. SV represents the diﬀerence between EDV (amount of blood that collects in a ventricle during diastole) and ESV (volume of blood remaining in the ventricle a er contrac on). SV = EDV - ESV. According to Frank – Starling law of the heart, the cri cal factor controlling SV is the degree to which the cardiac muscle cells are stretched just before they contract. The most important factor in stretching cardiac muscle is the amount of blood returning to the heart and distending its ventricles, 33 venous return. During vigorous exercise, SV may double because of venous return. Heart’s pumping ac on normally maintains a balance between cardiac output and venous return. Because the heart is a double pump, each side can fail independently of the other. If the le side of the heart fails, it results in pulmonary conges on and if the right side fails, it results in peripheral conges on. Frank – Starling eﬀect protects the heart from abnormal increase in blood volume. Blood Pressure Blood pressure is the pressure exerted on the surface of blood vessels by the blood. This pressure circulates the blood through arteries, veins and capillaries. There are two types of pressure, the systolic pressure and the diastolic pressure. Systolic pressure is the pressure in the arteries as the chambers of the heart contracts. Diastolic pressure is the pressure in the arteries when the heart chambers relax. Blood pressure is measured using a sphygmomanometer (BP apparatus). It is expressed as systolic pressure / diastolic pressure. Normal blood pressure in man is about 120/80mm Hg. Mean arterial pressure is a func on of cardiac output and resistance in the arterioles. The primary reﬂex pathway for homeosta c control of mean arterial pressure is the baroreceptor reﬂex. The baroreceptor reﬂex func ons every morning when you get out of bed. When you are lying ﬂat the gravita onal force is evenly distributed. When you stand up, gravity causes blood to pool in the lower extremi es. The decrease in blood pressure upon standing is known as orthosta c hypotension. Orthosta c reﬂex normally triggers baroreceptor reﬂex. This results in increased cardiac output and increased peripheral resistance which together increase the mean arterial pressure. 34 Electrocardiogram (ECG) An electrocardiogram (ECG) records the electrical ac vity of the heart over a period of me using electrodes placed on the skin, arms, legs and chest. It records the changes in electrical poten al across the heart during one cardiac cycle. The special ﬂap of muscle which ini ates the heart beat is called as sinoatrial node or SA node in the right atrium. It spreads as a wave of contrac on in the heart. The waves of the ECG are due to depolariza on and not due to contrac on of the heart. This wave of depolarisa on occurs before the beginning of contrac on of the cardiac muscle. A normal ECG shows 3 waves designated as P wave, QRS complex and T wave. P wave = spread of excita on wave over the atria just before contrac on; QRS wave = spread of excita on wave over the ventricles as the ventricles contract; T wave = electrical recovery and relaxa on of ventricles. A heart atack or myocardial infarc on (MI) can be recognized by an eleva on in the ST segment of the electrocardiographic tracing. Thus, one type of MI is an ST eleva on MI (STEMI). 35 P Wave (Atrial Depolarisa on) It is a small upward wave and indicates the depolarisa on of the atria. This is the me taken for the excita on to spread through atria from SA node. Contrac on of both atria lasts for around 0.8- 1.0 sec. PQ Interval (AV Node Delay) It is the onset of P wave to the onset of QRS complex. This is from the start of depolarisa on of the atria to the beginning of ventricular depolarisa on. It is the me taken for the impulse to travel from the atria to the ventricles (0.12-0.21sec). It is the measure of AV conduc on me. QRS Complex (Ventricular Depolarisa on) No separate wave for atrial depolarisa on in the ECG is visible. Atrial depolarisa on occurs simultaneously with the ventricular depolarisa on. The normal QRS complex lasts for 0.06-0.09 sec. QRS complex is shorter than the P wave, because depolarisa on spreads through the Purkinjie ﬁbres. Prolonged QRS wave indicates delayed conduc on through the ventricle, o en caused due to ventricular hypertrophy or due to a block in the branches of the bundle of His. ST Segment It lies between the QRS complex and T wave. It is the me during which all regions of the ventricles are completely depolarised and reﬂects the long plateau phase before repolarisa on. In the heart muscle, the prolonged depolarisa on is due to retarda on of K+ eﬄux and is responsible for the plateau. The ST segment lasts for 0.09 sec. 36 T wave (Ventricular Repolarisa on) It represents ventricular repolarisa on. The dura on of the T wave is longer than QRS complex because repolarisa on takes place simultaneously throughout the ventricular depolarisa on. Double Circula on Circula on of the blood was ﬁrst described by William Harvey (1628). There are two types of blood circula on in vertebrates, single circula on and double circula on. Arterioles Pulmonary artery Lung capillaries Pulmonary circula on Heart Venae cavae Veins and venules RV RA LA Systemic circula on Systemic capillaries LV Venules Pulmonary veins Aorta Arteries and arterioles The blood circulates twice through the heart ﬁrst on the right side then on the le side to complete one cardiac cycle. The complete double blood circula on is more prominent in mammals because of the complete par on of all the chambers (Auricles and ventricles) in the heart. In systemic circula on, the oxygenated blood entering the aorta from the le ventricle is carried by a network of arteries, arterioles and capillaries to the ssues. The deoxygenated blood from the ssue is collected by venules, veins and vena cava and emp ed into the right atrium. In pulmonary circula on, the blood from heart (right ventricle) is taken to the lungs by pulmonary artery and the oxygenated blood from the lungs is emp ed into the le auricle by the pulmonary vein. Completely separated circuits have an important advantage. Diﬀerent pressures are maintained in the pulmonary and systemic circula on. Why is 37 this advantageous? In the lungs the capillaries must be very thin to allow gas exchange, but if the blood ﬂows through these thin capillaries under high pressure the ﬂuid can leak through or ruptures the capillary walls and can accumulate in the ssues. This increases the diﬀusion distance and reduces the eﬃciency of the gas exchange. In contrast high pressure is required to force blood through the long systemic circuits. Hence the arteries close to the heart have increased pressure than the arteries away from the heart. Completely separated circuits (pulmonary and systemic) allow these two diﬀerent demands to be met with. Regula on of Cardiac Ac vity The type of heart in human is myogenic because the heartbeat originates from the muscles of the heart. The nervous and endocrine systems work together with paracrine signals (metabolic ac vity) to inﬂuence the diameter of the arterioles and alter the blood ﬂow. The neuronal control is achieved through autonomic nervous system (sympathe c and parasympathe c). Sympathe c neurons release nor-epinephrine and adrenal medulla releases epinephrine. The two hormones bind to β – adrenergic receptors and increase the heart rate. The parasympathe c neurons secrete acetylcholine that binds to muscarinic receptors and decreases the heartbeat. Vasopressin and angiotensin II, involved in the regula on of the kidneys, results in vasoconstric on while natriure c pep de promotes vasodila on. Vagus nerve is a parasympathe c nerve that supplies the atrium especially the SA and the AV nodes. 38 Vocabulary 1. Aorta - Largest artery in the body. 2. Arteriole - Small artery. 3. Artery - Largest type of blood vessel; carries blood away from the heart to all parts of the body. 4. Atrioventricular bundle (bundle of His) - Specialized muscle ﬁbers connec ng the atria with the ventricles and transmi ng electrical impulses between them. 5. Atrioventricular node (AV node) - Specialized ssue in the wall between the atria. Electrical impulses pass from the pacemaker (SA node) through the AV node and the atrioventricular bundle or bundle of His toward the ventricles. 6. Atrium - (plural: atria) One of two upper chambers of the heart. 7. Capillary - Smallest blood vessel. Materials pass to and from the bloodstream through the thin capillary walls. 8. Coronary arteries - Blood vessels that branch from the aorta and carry oxygen-rich blood to the heart muscle. 9. Deoxygenated blood - Blood that is oxygen-poor. 10. Diastole - Relaxa on phase of the heartbeat. From the Greek diastole, dila on. 11. Electrocardiogram - Record of the electricity ﬂowing through the heart. The electricity is represented by waves or deﬂec ons called P, QRS, or T. 12. Endocardium - Inner lining of the heart. 13. Endothelium - Innermost lining of blood vessels. 14. Mitral valve - Valve between the le atrium and the le ventricle; bicuspid valve. 15. Murmur - Abnormal swishing sound caused by improper closure of the heart valves. 16. Myocardium - Muscular, middle layer of the heart. 17. Normal sinus rhythm - Heart rhythm origina ng in the sinoatrial node with a res ng rate of 60 to 100 beats per minute. 18. Pacemaker (sinoatrial node) - Specialized nervous ssue in the right atrium that begins the heartbeat. An ar ﬁcial cardiac pacemaker is an electronic apparatus implanted in the chest to s mulate heart muscle that is weak and not func oning. 19. Pericardium - Double-layered membrane surrounding the heart. 20. Pulmonary artery - Artery carrying oxygen-poor blood from the heart to the lungs. 39 21. Pulmonary circula on - Flow of blood from the heart to the lungs and back to the heart. 22. Pulmonary valve - Valve posi oned between the right ventricle and the pulmonary artery. 23. Pulmonary vein - One of two pairs of vessels carrying oxygenated blood from the lungs to the le atrium of the heart. 24. Pulse - Beat of the heart as felt through the walls of the arteries. 25. Septum - Par on or wall dividing a cavity; such as between the right and le atria (interatrial septum) and right and le ventricles (interventricular septum). 26. Sinoatrial node (SA node) - Pacemaker of the heart. 27. Sphygmomanometer - Instrument to measure blood pressure. 28. Systemic circula on - Flow of blood from body ssue to the heart and then from the heart back to body ssues. 29. Systole - Contrac on phase of the heartbeat. From the Greek systole, a contrac ng. 30. Tricuspid valve - Located between the right atrium and the right ventricle; it has three (tri-) leaﬂets, or cusps. 31. Valve - Structure in veins or in the heart that temporarily closes an opening so that blood ﬂows in only one direc on. 32. Vein - Thin-walled vessel that carries blood from body ssues and lungs back to the heart. Veins contain valves to prevent backﬂow of blood. 33. Vena cava - (plural: venae cavae) Largest vein in the body. The superior and inferior venae cavae return blood to the right atrium of the heart. 34. Ventricle - One of two lower chambers of the heart. 35. Venule - Small vein. 36. Arrhythmias - Abnormal heart rhythms 37. Hypertrophic cardiomyopathy - Abnormal thickening of the heart muscle, usually in the le ventricle. 38. Bradycardia - Slower than 60 beats per minute. Normal pulse is about 60 to 80 beats per minute. 39. Tachycardia - Faster than 100 beats per minute. Supraventricular tachycardia (SVT) involves rapid beats coming from the atria (above the ventricles) and causing palpita on (abnormal sensa ons in the chest). 40 40. Cardiogenic shock - Results from failure of the heart in its pumping ac on. Shock is circulatory failure associated with inadequate delivery of oxygen and nutrients to body ssues. 41. Cyanosis - This bluish discolora on of the skin indicates diminished oxygen content of the blood. 42. Hypoxia - Inadequate oxygen in ssues. 43. Vasoconstric on - Constric on of the blood vessels 44. Fluter - Rapid but regular contrac ons, usually of the atria. 45. Fibrilla on - Very rapid, random, ineﬃcient, and irregular contrac ons of the heart (350 beats or more per minute). 46. Atrial ﬁbrilla on (AF) - Electrical impulses move randomly throughout the atria, causing the atria to quiver instead of contrac ng in a coordinated rhythm. 47. Palpita ons - Uncomfortable sensa ons in the chest from missed heartbeats. 48. Conges ve heart failure (CHF) - Heart is unable to pump its required amount of blood. 49. Coronary artery disease (CAD) - Disease of the arteries surrounding the heart. 50. Endocardi s - Inﬂamma on of the inner lining of the heart 51. Hypertension - It is the most common circulatory disease. The normal blood pressure in man is 120/80 mmHg. In cases when the diastolic pressure exceeds 90 mm Hg and the systolic pressure exceeds 150 mm Hg persistently, the condi on is called hypertension. Uncontrolled hypertension may damage the heart, brain and kidneys. 52. Hypertensive heart disease - High blood pressure aﬀec ng the heart 53. Stroke - is a condi on when the blood vessels in the brain bursts, (Brain haemorrhage) or when there is a block in the artery that supplies the brain, (atherosclerosis) or thrombus. The part of the brain ssue that is supplied by this damaged artery dies due to lack of oxygen (cerebral infarc on). 54. Angina Pectoris - (ischemic pain in the heart muscles) is experienced during early stages of coronary heart disease. Atheroma may par ally block the coronary artery and reduce the blood supply to the heart. As a result, there is ghtness or choking with diﬃculty in breathing. This leads to angina or chest pain. Usually, it lasts for a short dura on of me. 55. Myocardial Infarc on (Heart Failure) - The prime defect in heart failure is a decrease in cardiac muscle contrac lity. The Frank- Starling curve shi s downwards and towards the 41 right such that for a given EDV, a failing heart pumps out a smaller stroke volume than a normal healthy heart. When the blood supply to the heart muscle or myocardium is remarkably reduced it leads to death of the muscle ﬁbres. This condi on is called heart atack or myocardial infarc on. The blood clot or thrombosis blocks the blood supply to the heart and weakens the muscle ﬁbres. It is also called ischemic heart disease due to lack of oxygen supply to the heart muscles. If this persists it leads to chest pain or angina. Prolonged angina leads to death of the heart muscle resul ng in heart failure. 56. Rheumatoid Heart Disease - Rheuma c fever is an autoimmune disease which occurs 2- 4 weeks a er throat infec on usually a streptococcal infec on. The an bodies developed to combat the infec on cause damage to the heart. Eﬀects include ﬁbrous nodules on the mitral valve, ﬁbrosis of the connec ve ssue and accumula on of ﬂuid in the pericardial cavity. 57. Cardio Pulmonary Resuscita on (CPR) - CPR is a lifesaving procedure that is done at the me of emergency condi ons such as when a person’s breath or heart beat has stopped abruptly in case of drowning, electric shock or heart atack. CPR includes rescue of breath, which is achieved by mouth to mouth breathing, to deliver oxygen to the vic m’s lungs by external chest compressions which helps to circulate blood to the vital organs. CPR must be performed within 4 to 6 minutes a er cessa on of breath to prevent brain damage or death. Along with CPR, deﬁbrilla on is also done. Deﬁbrilla on means a brief electric shock is given to the heart to recover the func on of the heart. 58. Varicose veins - The veins are so dilated that the valves prevent back ﬂow of blood. The veins lose their elas city and become congested. Common sites are legs, rectal-anal regions (haemorrhoids), the oesophagus and the sperma c cord. 59. Embolism - is the obstruc on of the blood vessel by abnormal mass of materials such as fragment of the blood clot, bone fragment or an air bubble. Embolus may lodge in the lungs, coronary artery or liver and leads to death. 60. Aneurysm - The weakened regions of the wall of the artery or veins bulges to form a balloon like sac. Unruptured aneurysm may exert pressure on the adjacent ssues or may burst causing massive haemorrhage. 42 Urinary System Excretory system in human consists of a pair of kidneys, a pair of ureters, urinary bladder and urethra. Kidneys are reddish brown, bean shaped structures that lie in the superior lumbar region between the levels of the last thoracic and third lumber vertebra close to the dorsal inner wall of the abdominal cavity. The right kidney is placed slightly lower than the le kidney. Each kidney weighs an average of 120-170 grams. The outer layer of the kidney is covered by three layers of suppor ve ssues namely, renal fascia, perirenal fat capsule and ﬁbrous capsule. The longitudinal sec on of kidney shows, an outer cortex, inner medulla and pelvis. The medulla is divided into a few conical ssue masses called medullary pyramids or renal pyramids. The part of cortex that extends in between the medullary pyramids is the renal columns of Ber ni. The centre of the inner concave surface of the kidney has a notch called the renal hilum, through which ureter, blood vessels and nerves innervate. Inner to the hilum is a broad funnel shaped space called the renal pelvis with projec on called calyces. The renal pelvis is con nuous with the ureter once it leaves the hilum. The walls of the calyces, pelvis and ureter have smooth muscles which contracts rhythmically. The calyces collect the urine and emp es into the ureter, which is stored in the urinary bladder temporarily. The urinary bladder opens into the urethra through which urine is expelled out. 43 Structure of a Nephron Each kidney has nearly one million complex tubular structures called nephron. Each nephron consists of a ﬁltering corpuscle called renal corpuscle (malpighian body) and a renal tubule. The renal tubule opens into a longer tubule called the collec ng duct. The renal tubule begins with a double walled cup shaped structure called the Bowman’s capsule, which encloses a ball of capillaries that delivers ﬂuid to the tubules, called the glomerulus. The Bowman’s capsule and the glomerulus together cons tute the renal corpuscle. The endothelium of glomerulus has many pores (fenestrae). The external parietal layer of the Bowman's capsule is made up of simple squamous epithelium and the visceral layer is made of epithelial cells called podocytes. The podocytes end in foot processes which cling to the basement membrane of the glomerulus. The openings between the foot processes are called ﬁltra on slits. The renal tubule con nues further to form the proximal convoluted tubule [PCT] followed by a U-shaped loop of Henle (Henle’s loop) that has a thin descending and a thick ascending limb. The ascending limb con nues as a highly coiled tubular region called the distal convoluted tubule [DCT]. The DCT of many nephrons open into a straight tube called collec ng duct. The collec ng duct runs through the medullary pyramids in the region of the pelvis. Several collec ng ducts fuse to form papillary duct that delivers urine into the calyces, which opens into the renal pelvis. In the renal tubules, PCT and DCT of the nephron are situated in the cor cal region of the kidney whereas the 44 loop of Henle is in the medullary region. In majority of nephrons, the loop of Henle is too short and extends only very litle into the medulla and are called cor cal nephrons. Some nephrons have very long loop of Henle that run deep into the medulla and are called juxta medullary nephrons (JMN). The capillary bed of the nephrons- First capillary bed of the nephron is the glomerulus and the other is the peritubular capillaries. The glomerular capillary bed is diﬀerent from other capillary beds in that it is supplied by the aﬀerent and drained by the eﬀerent arteriole. The eﬀerent arteriole that comes out of the glomerulus forms a ﬁne capillary network around the renal tubule called the peritubular capillaries. The eﬀerent arteriole serving the juxta medullary nephron forms bundles of long straight vessel called vasa recta and runs parallel to the loop of Henle. Vasa recta is absent or reduced in cor cal nephrons. Mechanism of Urine Forma on in Human The nitrogenous waste formed as a result of breakdown of amino acids is converted to urea in the liver by the Ornithine cycle or urea cycle. Urine forma on involves three main processes namely, glomerular ﬁltra on, tubular reabsorp on and tubular secre on. i) Glomerular Filtra on: Blood enters the kidney from the renal artery, into the glomerulus. Blood is composed of large quan es of water, colloidal proteins, sugars, salts and nitrogenous end product. The ﬁrst step in urine forma on is the ﬁltra on of blood that takes place in the glomerulus. This is called glomerular ﬁltra on which is a passive process. The ﬂuid that leaves the glomerular capillaries and enters the Bowman’s capsule is called the glomerular ﬁltrate. The glomerular membrane has a large surface area and is more permeable to water and small molecules present in the blood plasma. Blood enters the glomerulus faster with greater force through the aﬀerent arteriole and leaves the glomerulus through the eﬀerent arterioles, much slower. This force is because of the diﬀerence in sizes between the aﬀerent and eﬀerent arteriole (aﬀerent arteriole is wider than eﬀerent arteriole) and glomerular hydrosta c pressure which is around 55mm Hg. Kidneys produce about 180L of glomerular ﬁltrate in 24 hours. The molecules such as water, glucose, amino acids and nitrogenous substances pass freely from the blood into the glomerulus. Molecules larger than 5nm are barred from entering the tubule. Glomerular pressure is the chief force that pushes water and solutes out of the blood and across the ﬁltra on membrane. The glomerular blood pressure (approximately 55 mmHg) is much higher than in other capillary beds. The two opposing forces are contributed by the plasma proteins in the capillaries. These includes, colloidal osmo c 45 pressure (30 mmHg) and the capsular hydrosta c pressure (15 mmHg) due to the ﬂuids in the glomerular capsule. The net ﬁltra on pressure of 10 mmHg is responsible for the renal ﬁltra on. Net ﬁltra on Pressure = Glomerular hydrosta c pressure - (Colloidal osmo c pressure + Capsular hydrosta c pressure). Net ﬁltra on pressure = 55 mmHg - (30 mmHg + 15 mmHg) = 10mmHg The eﬀec ve glomerular pressure of 10 mmHg results in ultraﬁltra on. Glomerular ﬁltra on rate (GFR) is the volume of ﬁltrate formed min21 in all nephrons (glomerulus) of both the kidneys. In adults the GFR is approximately 120- 125mL/min. Blood from the glomerulus is passed out through the eﬀerent arteriole. The smooth muscle of the eﬀerent arteriole contract resul ng in vasoconstric on. Table 8.1 shows the rela ve concentra ons of substances in the blood plasma and the glomerular ﬁltrate. The glomerular ﬁltrate is similar to blood plasma except that there are no plasma proteins. In cor cal nephrons, blood from eﬀerent arteriole ﬂows into peritubular capillary beds and enters the venous system carrying with it recovered solutes and water from the inters al ﬂuid that surrounds the tubule. Concentra on of substances in the blood plasma and in the glomerular ﬁltrate ii) Tubular Reabsorp on This involves movement of the ﬁltrate back into the circula on. The volume of ﬁltrate formed per day is around 170-180 L and the urine released is around 1.5 L per day, i.e., nearly 99% of the glomerular ﬁltrate that has to be reabsorbed by the renal tubules as it contains certain substances 46 needed by the body. This process is called selec ve reabsorp on. Reabsorp on takes place by the tubular epithelial cells in diﬀerent segments of the nephron either by ac ve transport or passive transport, diﬀusion and osmosis. Proximal Convoluted Tubule (PCT)- Glucose, lactate, amino acids, Na1 and water in the ﬁltrate is reabsorbed in the PCT. Sodium is reabsorbed by ac ve transport through sodium- potassium (Na1 K1) pump in the PCT. Small amounts of urea and uric acid are also reabsorbed. Descending limb of Henle’s loop is permeable to water due the presence of aquaporins, but not permeable to salts. Water is lost in the descending limb, hence Na1 and Cl2 gets concentrated in the ﬁltrate. Ascending limb of Henle’s loop is impermeable to water but permeable to solutes such as Na1, Cl2 and K1. The distal convoluted tubule recovers water and secretes potassium into the tubule. Na1, Cl2 and water remains in the ﬁltrate of the DCT. Most of the reabsorp on from this point is dependent on the body’s need and is regulated by hormones. Reabsorp on of bicarbonate (HCO32) takes place to regulate the blood pH. Homeostasis of K1 and Na1 in the blood is also regulated in this region. Aquaporins are water–permeable channels (membrane transport proteins) that allow water to move across the epithelial cells in rela on to the osmo c diﬀerence from the lumen to the inters al ﬂuid. Collec ng duct is permeable to water, secretes K1 (potassium ions are ac vely transported into the tubule) and reabsorbs Na1 to produce concentrated urine. The change in permeability to water is due to the presence aquaporins. Tubular secre on- Substances such as H1, K1, NH41, crea nine and organic acids move into the ﬁltrate from the peritubular capillaries into the tubular ﬂuid. Most of the water is absorbed in the proximal convoluted tubule and Na1 is exchanged for water in the loop of Henle. Hypotonic ﬂuid enters the distal convoluted tubule and substances such as urea and salts pass from peritubular blood into the cells of DCT. The urine excreted contains both ﬁltered and secreted substances. Once it enters the collec ng duct, water is absorbed and concentrated hypertonic urine is formed. For every H1 secreted into the tubular ﬁltrate, a Na1 is absorbed by the tubular cell. The H1 secreted combines with HCO32, HPO32 and NH32 and gets ﬁxed as H2CO41, H2PO41 and NH41 respec vely. Since H1 gets ﬁxed in the ﬂuid, reabsorp on of H1 is prevented. Osmolarity - The solute concentra on of a solu on of water is known as the solu ons osmolarity, expressed as milliosmoles /liter (mOsm/L). 47 Forma on of concentrated urine Forma on of concentrated urine is accomplished by kidneys using counter current mechanisms. The major func on of Henle’s loop is to concentrate Na1 and Cl2. There is low osmolarity near the cortex and high osmolarity towards the medulla. This osmolarity in the medulla is due to the presence of the solute transporters and is maintained by the arrangement of the loop of Henle, collec ng duct and vasa recta. This arrangement allows movement of solutes from the ﬁltrate to the inters al ﬂuid. At the transi on between the proximal convoluted tubule and the descending loop of Henle the osmolarity of the inters al ﬂuid is similar to that of the blood – about 300mOsm. Ascending and descending limbs of Henle, create a counter current mul plier (interac on between ﬂow of ﬁltrate through the limbs of Henle’s and JMN) by ac ve transport. (a) shows the counter current mul plier created by the long loops of Henle of the JM nephrons which creates medullary osmo c gradient. As the ﬂuid enters the descending limb, water moves from the lumen into the inters al ﬂuid and the osmolarity of inters al ﬂuid decreases. To counteract this dilu on the region of the ascending limb ac vely pumps solutes from the lumen into the inters al ﬂuid and the osmolarity increases to about 1200mOsm in medulla. This mismatch between water and salts creates osmo c gradient in the medulla. The osmo c gradient is also due to the permeability of the collec ng duct to urea. The vasa recta, maintains the medullary osmo c gradient via counter current exchanger (the ﬂow of blood through the ascending and descending vasa recta blood vessels) by passive transport. (b) shows counter current exchanger where the vasa recta preserves the medullary gradient while removing reabsorbed water and solutes. This system does not produce an osmo c gradient, but protects the medulla by removal of excess salts from the inters al ﬂuid and removing reabsorbed water. The vasa recta leave the kidney at the junc on between the cortex and medulla. The inters al ﬂuid at this point is iso-osmo c to the blood. When the blood leaves the eﬀerent arteriole and enters vasa recta the osmolarity in the medulla increases (1200mOsm) and results in passive uptake of solutes and loss of water in descending vasa recta. As the blood enters the cortex, the osmolarity in the blood decreases (300mOsm) and the blood loses solutes and gains water. At the ﬁnal stage in collec ng duct to form concentrated urine (hypertonic). Human kidneys can produce urine nearly four mes concentrated than the ini al ﬁltrate formed. 48 Regula on of Kidney Func on ADH and Diabetes Insipidus The func oning of kidneys is eﬃciently monitored and regulated by hormonal feedback control mechanism involving the hypothalamus, juxta glomerular apparatus and to a certain extent the heart. Osmoreceptors in the hypothalamus are ac vated by changes in the blood volume, body ﬂuid volume and ionic concentra on. When there is excessive loss of ﬂuid from the body or when there is an increase in the blood pressure, the osmoreceptors of the hypothalamus respond by s mula ng the neurohypophysis to secrete the an diure c hormone (ADH) or vasopressin (a posi ve feedback). ADH facilitates reabsorp on of water by increasing the number of aquaporins on the cell surface membrane of the distal convoluted tubule and collec ng duct. This increase in aquaporins causes the movement of water from the lumen into the inters al cells, thereby preven ng excess loss of water by diuresis. When you drink excess amounts of your favourite juice, osmoreceptors of the hypothalamus is no longer s mulated and the release of ADH is suppressed from the neurohypophysis (nega ve feedback) and the aquaporins of the collec ng ducts move into the cytoplasm. This makes the collec ng ducts impermeable to water and the excess ﬂuid ﬂows down the collec ng duct without any water loss. Hence dilute urine is produced to maintain the blood volume. Vasopressin secre on is controlled by posi ve and nega ve feedback mechanism. Defects in ADH receptors or inability to secrete ADH leads to a condi on called diabetes insipidus, characterized by excessive thirst and excre on of large quan es of dilute urine resul ng in dehydra on and fall in blood pressure. 49 Renin Angiotensin Juxta glomerular apparatus (JGA) is a specialized ssue in the aﬀerent arteriole of the nephron that consists of macula densa and granular cells. The macula densa cells sense distal tubular ﬂow and aﬀect aﬀerent arteriole diameter, whereas the granular cells secrete an enzyme called renin. A fall in glomerular blood ﬂow, glomerular blood pressure and glomerular ﬁltra on rate, can ac vate JG cells to release renin which converts a plasma protein, angiotensinogen (synthesized in the liver) to angiotensin I. Angiotensin conver ng enzyme (ACE) converts angiotensin I to angiotensin II. Angiotensin II s mulates Na1 reabsorp on in the proximal convoluted tubule by vasoconstric on of the blood vessels and increases the glomerular blood pressure. Angiotensin II acts at diﬀerent sites such as heart, kidney, brain, adrenal cortex and blood vessels. It s mulates adrenal cortex to secrete aldosterone that causes reabsorp on of Na1, K1 excre on and absorp on of water from the distal convoluted tubule and collec ng duct. This increases the glomerular blood pressure and glomerular ﬁltra on rate. This complex mechanism is generally known as Renin- Angiotensin- Aldosterone System (RAAS). shows the schema c representa on of the various hormones in the regula on of body ﬂuid concentra on. Atrial Natriure c Factor Excessive stretch of cardiac atrial cells cause an increase in blood ﬂow to the atria of the heart and release Atrial Natriure c Pep de or factor (ANF) travels to the kidney where it increases Na1 excre on and increases the blood ﬂow to the glomerulus, ac ng on the aﬀerent glomerular arterioles as a vasodilator or on eﬀerent arterioles as a vasoconstrictor. It decreases aldosterone release from the adrenal cortex and also decreases release of renin, thereby decreasing angiotensin II. ANF acts antagonis cally to the renin- angiotensin system, aldosterone and vasopressin. Micturi on The process of release of urine from the bladder is called micturi on or urina on. Urine formed by the nephrons is ul mately carried to the urinary bladder where it is stored ll it receives a voluntary signal from the central nervous system. The stretch receptors present in the urinary bladder are s mulated when it gets ﬁlled with urine. Stretching of the urinary bladder s mulates the CNS via the sensory neurons of the parasympathe c nervous system and brings about contrac on of the bladder. Simultaneously, soma c motor neurons induce the sphincters to close. Smooth muscles contracts 50 resul ng in the opening of the internal sphincters passively and relaxing the external sphincter. When the s mulatory and inhibitory controls exceed the threshold, the sphincter opens and the urine is expelled out. An adult human on an average excretes 1 to 1.5 L of urine per day. The urine formed is a yellow coloured watery ﬂuid which is slightly acidic in nature (pH 6.0), Changes in diet may cause pH to vary between 4.5 to 8.0 and has a characteris c odour. The yellow colour of the urine is due to the presence of a pigment, urochrome. On an average, 25-30 gms of urea is excreted per day. Various metabolic disorders can aﬀect the composi on of urine. Analysis of urine helps in clinical diagnosis of various metabolic disorders and the malfunc oning of the kidneys. For example the presence of glucose (glucosuria) and ketone bodies (ketonuria) in the urine are indica ons of diabetes mellitus. Hypotonic urine is formed when osmo c pressure of the body ﬂuid is decreased due to water reten on or solute loss when ADH secre on is lowered. If you drink large volume of water without ea ng anything salty, the total body ﬂuid volume increases quickly and the osmolarity decreases. The kidneys increase the volume of urine excreted. The reverse happens when you eat salty food without drinking water. Role of other Organs in Excre on Apart from kidneys, organs such as lungs, liver and skin help to remove wastes. Our lungs remove large quan e

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