Module 2: Excretion F214 Communication, homeostasis and energy Learning Outcomes • Define the term excretion. • Explain the importance of removing metabolic wastes, including carbon dioxide and nitrogenous waste, from the body. Excretion • Excretion is the removal of unwanted products of metabolism • Main products – carbon dioxide – urea Carbon dioxide • Produced in every living cell during aerobic respiration • Transported in the blood stream Carbon Dioxide Transport • CO2 carried in three ways – 5% in solution in plasma as CO2 – 10% combines with amino groups in Hb molecule (carbamino haemoglobin) – 85% hydrogen carbonate ions Carbon dioxide transport • Transported in blood as hydrogen carbonate ions • Carbonic anhydrase catalyses the reaction CO2 + H2O H2CO3 Carbon Dioxide Transport • Carbonic acid dissociates H2CO3 H+ + HCO3• H+ ions associate with haemoglobin (buffer) Haemoglobinic acid (HHb) Chloride Shift • Build up HCO3- causes them to diffuse out of RBC • Inside membrane positively charged • Cl- diffuse into RBC from plasma to balance the electrical charge What happens if CO2 is not excreted? • Carbon dioxide is toxic – Hydrogen carbonate ions can reduce the ability to transport oxygen – Forms carbaminohaemoglobin which has a lower affinity for oxygen than normal haemoglobin – Respiratory acidosis • Drop in blood pH – Headache, drowsiness, restlessness, tremor and confusion Learning Outcomes • Describe the formation of urea in the liver, including an outline of the ornithine cycle. Urea • Produced by the liver from excess amino acids • Deamination • Urea formation • Transported from the liver to the kidneys in the blood stream, where it is excreted dissolved in water, as urine. Amino acid + oxygen keto acid + ammonia Ammonia + carbon dioxide urea + water Urea Formation • Amino Acid molecules contain a lot of energy • Urea is formed from two processes – Deamination – Ornithine cycle Amino acid ammonia urea deamination Ornithine cycle Deamination • Amine group (NH2) of each amino acid is removed • Ammonia (NH3) is formed which is highly soluble and highly toxic • Keto acid can enter respiration to release energy or stored as fat deamination Ornithine Cycle • Ammonia is quickly converted into the less soluble and less toxic urea CO(NH2)2 • The ornithine cycle requires the input of energy from ATP The ornithine cycle Citruline CO2 Ammonia NH3 ATP ornithine ATP ADP ADP arginine Urea CO(NH2)2 Learning Outcomes • Describe, with the aid of diagrams and photographs, the histology and gross structure of the liver. The liver and it’s associated organs Histology. • The liver lies below the diaphragm and just to the right of centre. • Its is supplied by two different blood supplies, the hepatic artery brings oxygenated blood from the aorta, the hepatic portal vein delivers blood from the digestive tract. Histology • Blood is carried away by the hepatic vein to the vena cava. • 75% of the blood delivered to the liver arrives via the hepatic portal vein at a very low pressure. Histology of the liver • The liver is divided into two principal lobes • The lobes are subdivided into about 100,000 lobules. Histology of liver Liver Lobules Liver Lobules lobules • Each lobule is a six sided structure consisting of specialised epithelial cells called hepatocytes. • The lobules are arranged in irregular, branching, interconnected plates around a central vein. • The blood passes through large endothelium-lined spaces called sinusoids. sinusoids • Within the sinusoids there are fixed phagocytes called Kupffer cells. – The role of these is to destroy worn out red and white blood cells, bacteria and foreign matter arriving from the digestive tract. • Blood flows from the hepatic portal vein and hepatic artery towards the centre of the lobule, where it enters a central vein leading to the hepatic vein. Liver Lobule Liver Lobule Bile Duct • Running alongside the sinusoids are bile canaliculi. • These carry bile from the centre of the lobule to the outside, where it enters a branch of the bile duct. • The bile ducts merge and form the larger right and left hepatic ducts. Learning Outcomes • Describe the roles of the liver in detoxification Detoxification • Detoxification can take place by the oxidation, reduction or methylation of toxins • Detoxification of alcohol, antibiotics, steroid hormones etc • Example catalase Hydrogen peroxide water and oxygen 2H2O2 2H2O + O2 Detoxification of alcohol • Alcohol is broken down into ethanoate by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase. • Ethanoate enters the Krebs cycle and is metabolised to produce ATP. • Reduced NAD is produced Detoxification of alcohol Fatty Liver • NAD is used to oxidise fatty acids in the liver – If NAD is reduced it can not oxidise the fatty acids, which accumulate and are converted into fat – The fat is deposited in the liver Cirrhosis • Damaged hepatocytes are replaced by fibrous tissue • Structure of blood supply is lost – Blood flows from hepatic artery into hepatic vein without flowing through sinusoids • Effects – Increase in ammonia concentration which can cause major damage to the central nervous system Pupil Activity • Answer the question sheet on the liver • Answer the past paper questions on the liver • Answer the stretch and challenge question on page 41 of your textbook. The Kidneys Module 2: Excretion Learning Outcomes • Describe, with the aid of diagrams and photographs, the histology and gross structure of the kidney. • Describe, with the aid of diagrams and photographs, the detailed structure of a nephron and its associated blood vessels. Position of the kidney and associated structures in the human body Kidney cut in half The structure of the nephron • Each kidney is made up of thousands of tiny tubes called nephrons The Nephron • Bowman’s capsule • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule • Collecting duct Nephron • Blood supply Afferent arteriole glomerulus efferent arteriole Kidney Function • Cortex – Filtration is carried out by the nephrons. – Dense capillary network which receives blood from renal artery. • Medulla – Nephron extends across to form renal pyramids • Pelvis – Renal pyramids project into a central space called the pelvis. – Urine passes from the pelvis into the ureter Learning Outcomes • Describe and explain the production of urine, with reference to the processes of ultrafiltration and selective reabsorption. Revision • On a sheet of A4 plain paper – Draw and label the cross section of a kidney – Draw and label a nephron • Swap your sheets over for marking – both are to be marked out of 10 • What is your total out of 20? The Nephron 1. Ultrafiltration 2. Selective reabsorption in the proximal convoluted tubule 3. Reabsorption of water in the loop of Henlé (counter current system) 4. Reabsorption in the distal convoluted tubule and the collecting duct. Ultrafiltration in the renal capsule • The blood in the capillaries is separated from the lumen of the renal capsule by – Endothelium – basement membrane – Podocytes • The endothelium of the renal capsule Podocytes Ultrafiltration in the renal capsule • Gaps allow most molecules to pass through • Basement membrane – prevents large molecules e.g. plasma proteins, from passing through. Ultrafiltration • High pressure maintained as afferent arteriole is wider than efferent arteriole. • Hydrostatic pressure builds up forcing substances through endothelial pores, across basement membrane and into Bowman’s capsule. • The fluid in the renal capsule is known as glomerular filtrate Comparison of blood and glomerular filtrate substance Concentration in blood plasma (g dm-3) Concentration in glomerular filtrate (g dm-3) Water 900 900 Inorganic ions 7.2 7.2 Urea 0.3 0.3 Uric acid 0.04 0.04 Glucose 1.0 1.0 Amino acids 0.5 0.5 proteins 80.0 0.05 selective reabsorption • All glucose, amino acids, vitamins and many sodium and chloride ions are reabsorbed out of the proximal convoluted tubule and back into the blood. • The walls of the nephron are made up of cuboidal epithelium with microvilli – give LSA • Blood capillaries lie close to the outer surface of tubule Selective reabsorption • Outer membranes of cells actively transport sodium ions out of cytoplasm (sodium potassium pump) • Sodium ions diffuse down a concentration gradient back into the cytoplasm, passing through cotransporter proteins that transport glucose or amino acids Selective reabsorption 1. Sodium ions are actively transported out of cells into the tissue fluid 2. Glucose or amino acids enter cells with sodium ions by facilitated diffusion 3. Glucose and amino acids diffuse into the blood capillary Selective reabsorption • Reabsorption of salts, glucose and amino acids – reduces the water potential of cells – Increases water potential in tubule • Water is reabsorbed into the blood by osmosis Learning outcomes • Explain, using water potential terminology, the control of the water content of the blood, with reference to the roles of the kidney, osmoreceptors in the hypothalamus and the posterior pituitary gland. Reabsorption of water • The Loop of Henlé – Function • Create a high concentration of sodium ions and chloride ions in the tissue fluid of the medulla – Why? • Allows water to be reabsorbed from the contents of the nephron as they pass through collecting duct – Survival advantage • Very concentrated urine can be produced • Conserves water and prevents dehydration The loop of Henlé • Descending limb – Water-permeable • Ascending limb – more permeable to salts/less permeable to water. The loop of Henlé 1. Upper part of ascending limb • Active transport of sodium and chloride ions out of the nephron • Increases water potential of fluid inside nephron • Decreases water potential outside it 2. Descending limb • Water moves down a water potential gradient from nephron and into surrounding tissues The loop of Henlé 3. Lower part of ascending limb • • • Fluid is very concentrated Sodium and chloride ions diffuse out into the surrounding tissues Counter-current system – – Solute concentration at any part of the ascending tubule is lower than that in the descending limb. Causes a build up of salt concentration in the surrounding tissues Distal convoluted tubule and collecting duct • DCT – Sodium ions actively pumped out of nephron into blood. • 2nd part DCT – acts as collecting duct – regulating how much water passes into the medulla (and urine concentration). Reabsorption of water from the collecting duct Reabsorption of water in the collecting duct • Tissue fluid deep in the medulla has a very low water potential • Water moves down a water potential gradient and enters the blood by osmosis Conservation of water • The longer the loop of Henlé • The lower the water potential can be built up • Greater the water potential gradient • More water reabsorbed • Smaller volume of concentrated urine produced Osmoregulation • Learning outcomes – Explain, using water potential terminology, the control of the water content of the blood, with reference to the roles of the kidney, osmoreceptors in the hypothalamus and the posterior pituitary gland Osmoregulation • Osmoregulation is the control of water content of the body • It is an example of negative feedback • Negative feedback – – – – – stimulus Receptor Message Effector response Osmoregulation • Osmoreceptors in the hypothalamus are sensitive to the water potential of the blood • Cell bodies of neurosecretory produce ADH (anti-diuretic hormone) • ADH passes along the axon which terminates in the posterior pituitary gland • ADH released into the blood ADH • Synthesised in the hypothalamus • Secreted from the pituitary gland • Target cells – cells lining the collecting duct – ADH attaches to cell surface membrane – Vesicles containing aquaporins move to the plasma membrane – Forming channels that allow water molecules to pass through Learning Outcomes • Describe how urine samples can be used to test for pregnancy and detect misuse of anabolic steroids. Urine Sampling • Urine contains many waste products of metabolism • This can be tested and used to diagnose illness • Examples – Early diagnosis of pregnancy – Evidence for the misuse of drugs Pregnancy testing • Most pregnancy test kits use monoclonal antibodies to test for the presence of HCG (human chorionic gonadotrophin) in the urine. • The antibodies bind with HCG. How a dipstick works • HCG-specific antibodies are coated with gold atoms • Anti-body gold complexes coat the end of the dipstick • Further up the dipstick in the Patient Test Result region are monoclonal anti-bodies which bind to the HCG-antibodygold complex. How the dipstick works Anabolic steroids • Anabolic steroids stimulate anabolic reactions in the body – Large molecules are built up from smaller ones • Steroids are – Derived from cholesterol – Lipid soluble – Increase protein synthesis inside the cell Anabolic Steroids • Urine testing – Gas chromatography to create a chromatogram – Test for presence of nandrolone – Although difficult to ascertain what is an abnormal level Learning Outcomes • Outline the problems that arise from kidney failure and discuss the use of renal dialysis and transplants for the treatment of kidney failure. Kidney failure • Renal dialysis – Haemodialysis – Peritoneal dialysis • Kidney transplant – Dues to a shortage of donors scientists are studying the possibility of a xenotransplant. Haemodialysis Haemodialysis • Blood from the patient’s vein is passed through very small tubes made from a partially permeable membrane. • On the outside of the membrane, dialysis fluid flows in the opposite direction. • The fluid has the water potential and concentration of ions and glucose that the patient’s blood should have. Peritoneal dialysis • Peritoneum is the layer of tissue that lines the abdominal cavity. • A catheter is inserted into the peritoneum cavity • Dialysis fluid is passed in and left there • Fluid is drained off.