5.2- excretion as an example of homeostatic control
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Made using Pearson textbook and the specification. Covers the liver and kidneys.
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* Nitrogen-containing compounds, such as urea
* Other compounds, such as the bile pigments found in faeces
* In the lungs, the carbon dioxide diffuses into the alveoli to be excreted as you breathe out
* The liber is involved in converting excess amino acids to urea
* Amino acids are broken down by deamination
* The nitrogen containing part of the molecule is then combined with carbon dioxide to make urea
* Urea is transported in solution- dissolved in the plasma
* In the kidneys the urea is removed from the blood to become a part of the urine
* Urine is stored in the bladder before being excreted from the body via the urethra
* Urea, uric acid and ammonia are all excretory products
* The loss of water and salts may be an important part of homeostasis- maintaining the body temperature and water potential of the blood
* Some metabolic products such as carbon dioxide and ammonia are toxic- they interfere with cell processes by altering the pH, so that normal metabolism is prevented
* Other metabolic products may act as inhibitors and reduce the activity of essential enzymes
* This reduces the affinity of haemoglobin for oxygen, affecting oxygen transport
* The hydrogen ions can then combine with haemoglobin, forming haemoglobinic acid
* The carbon dioxide that is not converted to hydrogencarbonate ions can combine directly with haemoglobin, forming carbaminohaemoglobin
* Both haemoglobinic acid and carbaminohaemoglobin are unable to combine with oxygen as normal
* Proteins in the blood act as buffers to resist the change in pH
* There may also be a rapid heart rate and changes in blood pressure
* This is respiratory acidosis- it can be caused by diseases or conditions that affect the lungs themselves
* They are transported to the liver and the potentially dangerous amino group is removed- deamination
* The amino group is converted to a less soluble and less toxic compound called urea, which can be transported to the kidneys for excretion
* The remaining keto acid can be used directly in respiration to release its energy or it may be converted to a carbohydrate or fat for storage
Formation of urea : ammonia + carbon dioxide = urea + water
2NH3 + CO2 = (NH2)2CO2 + H2O
* The internal structure of the liver ensures that as much blood as possible flows as past as many liver cells as possible
* This enables the liver cells to remove excess or unwanted substances from the blood and return substances to the blood to ensure concentrations are maintained
* The liver cells are very active as they carry out lots of metabolic processes, and these require energy
* This blood is rich in the products of digestion
* The concentrations of various substances will be uncontrolled as they have just entered the body from the products of digestion in the intestines
* The blood may also contain toxic compounds that have been absorbed from the intestine, so these should not circulate around the body
* Blood leaves the liver via the hepatic vein
* The hepatic vein rejoins the vena cava and the blood returns to the body’s normal circulation
* The bile duct carries bile from the liver to the gallbladder where it is stored until required to aid the digestion of fats in the small intestine
* Bile also contains some excretory products such as bile pigments like bilirubin, which will leave the body with faeces
* At intervals, branches from the hepatic artery and hepatic portal vein enter the lobules
* The blood from the two blood vessels is mixed and passes along a sinusoid which is lined with liver cells
* As the blood flows along the sinusoid, it is in closer contact with the liver cells. These cells are then able to remove substances from the blood and return other substances to the blood
* When the blood reaches the end of the sinusoid, the concentrations of many of its components have been modified and regulated
* At the centre of each lobular is a branch of the hepatic vein known as the intra-lobular vessel, and the sinusoids empty into this
* The branches of the hepatic vein, from different lobules join together to form the hepatic vein, which drains blood from the liver
* They have a simple cuboidal shape with many micro bills on their surface
* Their many metabolic functions include protein synthesis, transformation and storage of carbohydrates, synthesis of cholesterol and bile salts, detoxification, and others processes
* This means their cytoplasm must be very dense and is specialised in the numbers of certain organelles it contains
* Synthesis of plasma proteins, bile and cholesterol
* Synthesis of red blood cells in the foetus
* Storage of vitamins A, D and B12, iron and glycogen
* Detoxification of alcohol and drugs
* Breakdown of hormones
* Destruction of red blood cells
* The glycogen forms granules in the cytoplasm of the hepatocytes
* This glycogen can be broken down to release glucose into the blood as required
* Liver cells contain many enzymes that render toxic molecules less toxic
Catalase has a particularly high turnover number of five million
* The cytochromes are also used in other metabolic reactions, such as electron transport during respiration
* Their role in metabolising drugs can interfere with other metabolic roles and cause unwanted side effects of some medicinal drugs
* This is dehydrogenated further by ethanal dehydrogenase
* The final compound produced is ethanoate
* This acetate is combined with coenzyme A to form acetyl coenzyme A, which enters the process of aerobic respiration
* The hydrogen atoms released from alcohol are combined with NAD to form reduced NAD
* If the liver has to detoxify too much alcohol, it uses up its stores of NAD and has insufficient left to deal with fatty acids
* These are then converted directly back to lipids and stored as fat inn the hepatocytes, causing the liver to become enlarged
* This is called fatty liver, which can lead to hepatitis or cirrhosis
* Excess amino acids cannot be stored, because the amino groups make them toxic
* However, the amino acid molecules contain a lot of energy, so it would be wasteful to excrete the whole molecule
* Excess amino acids undergo treatment in the liver to remove and excrete the amino component
* This treatment consists of two processes- deamination followed by the ornithine cycle
* Ammonia is very soluble and highly toxic
* Ammonia must not be allowed to accumulate
* Deamination also produces an organic compound, a keto acid, which can enter respiration directly to release its energy
* The ammonia is combined with carbon dioxide to produce urea
* This occurs in the ornithine cycle
* Ammonia and carbon dioxide combine with the amino acid ornithine to produce citrulline
* This is converted to arginine by addition of further ammonia
* This arginine is then re-converted to ornithine by the removal of urea
* Urea is both less soluble and toxic than ammonia
* It can be passed back into the blood and transported around the body to the kidneys
* In the kidneys the urea is filtered out of the blood and concentrated in the urine
* Urine can be safely stored in the bladder until it is released from the body
The structure of the kidney
Most people have two kidneys, positioned on each side of the spine, just below the lowest rib
Each kidney is supplied with blood from a renal artery and is drained by a renal vein
The kidneys remove waste products from the blood and produce urine. The urine passes out of the kidney down the ureter to the bladder where is can be stored until it is released
What three regions does the kidney consist of?
Outer region = cortex
Inner region = medulla
Centre = pelvis, leads into ureter
The fine structure of the kidney
Bulk of the kidney consists of tubules called nephrons
Each nephron starts in the cortex at a cup-shaped structure called the Bowman’s capsule
The remainder of the nephron is a coiled tubule that passes through the cortex, forms a loop down into the medulla and back to the cortex, before joining a collecting duct that passes back down into the medulla
What is the glomerulus?
The renal artery splits to form many arteriolar, which each lead to a knot of capillaries called the glomerulus
Where does blood from the glomerulus go?
Continues into an efferent arteriole which carries the blood to more capillaries surrounding the rest of the tubule, these capillaries eventually flow together into the renal vein. Each glomerulus is surrounded by the Bowman’s capsule. Fluid from the blood is pushed int the capsule by ultrafiltration.
The endothelium of the capillary
Narrow gaps between the cells of the endothelium of the capillary wall. The cells of the endothelium also contain pores called fenestrations. The gaps allow blood plasma and the substances dissolved in it to pass out of the capillary.
The basement membrane
Consists of a fine mesh of collagen fibres and glycoproteins, this mesh acts as a filter to prevent the passage of molecules with a relative molecular mass greater then 69,000. Most proteins and all bloos cells are held in the capillaries of the glomerulus.
The epithelial cells of the Bowman’s capsule
Podocytes have finger-like projections called major processes, which have minor processes that hold the cells away from the endothelium of the capillary. These projections ensure there are gaps between the cells. Fluid from the blood in the glomerulus can pass between these cells into the lumen of the Bowman’s capsule.
What are the three parts of the tubule?
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
The fluid from many nephrons enters the collecting ducts, which pass down through the medulla to the pelvis at the centre of the kidney.
Ultrafiltration
The filtering of blood at the molecular level.
Blood flows into the glomerulus through the afferent arteriole, which is wider than the efferent arteriole that carries blood away from the glomerulus.
The difference in diameters ensures the blood in the capillaries of the glomerulus maintains a pressure higher than the pressure in the Bowman’s capsule
This pressure difference pushes fluid from the blood into the Bowman’s capsule that surrounds the glomerulus
What does the blood plasma contain?
Water
Amino acids
Glucose
Urea
Inorganic mineral ions- sodium, chloride, potassium
What is left in the capillary?
Blood cells and proteins. The presence of proteins means the blood has a very low water potential, ensuring some fluid is retained in the blood. The low water potential of the blood in the capillaries is important to help re absorb water at a later stage.
What happens as the fluid from the Bowman’s capsule passes along the nephron tubule?
Its composition is altered by selective reabsorption- substances are absorbed back into the tissue fluid and blood capillaries surrounding the nephron.
What happens in the proximal convoluted tubule?
The fluid is altered by the reabsorption of all of the sugars, most mineral ions, and some water
About 85% of the fluid is reabsorbed here
The cells of these tubules have a highly folded surface producing a brush border which increases the surface area
What happens in the descending limb of the loop of Henle?
The water potential of the fluid is decreased by the addition of mineral ions and the removal of water
What happens in the ascending limb of the loop of Henle?
The water potential is increased as mineral ions are removed by active transport
What happens in the collecting duct?
The water potential is decreased again by the removal of water. The final product in the collecting duct is urine.
What does this process ensure?
The final product has a low water potential. The urine therefore has a higher concentration of solutes than is found in the blood and tissue fluid. Urine passes into the pelvis and down the ureter to the bladder.
What does reabsorption involve?
Active transport and cotransport. The cells lining the proximal convoluted tubule are specialised to achieve reabsorption.
What are the specialisations of cells for achieving reabsorption?
The cell surface membrane in contact with the tubule fluid is highly folded to form microvilli, increasing the surface area for reabsorption
The cell surface membrane contains cotransport proteins that transport glucose or amino acids in association with sodium ions from the tubule into the cell
The opposite membrane of the cell close to the tissue fluid and blood capillaries is folded to increase surface area. This membrane contains sodium / potassium pumps that pump sodium ions out of the cell and potassium ions into the cell
The cell cytoplasm has many mitochondria, indicating an active process is involved
What is the movement of sodium ions and glucose into the cell driven by?
The concentration gradient created by pumping sodium ions out of the cell
Where do the sodium ions move?
Into the cell by facilitated diffusion but they cotransport glucose or amino acids against their concentration gradient- this is called secondary active transport
What does the movement of these substances do?
Reduces water potential of blood cells so water is drawn in from the tubule by osmosis. As the substances move through to the blood, the water follows
Describe the mechanism of selective reabsorption
1) Sodium ions are actively pumped out of the cells lining the tubule
2) Concentration of sodium ions in a cell cytoplasm decreases, creating a concentration gradient
3) Sodium ions diffuse into the cell through a cotransport protein- carrying glucose or an amino acid at the same time
4) Water moves into the cell by osmosis
5) Glucose and amino acids diffuse into the blood
What does the loop of Henle consist of?
A descending limb that descends into the medulla and an ascending limb that ascends back out to the cortex.
What does the arrangement of the loop of Henle allow?
Allows mineral ions to be transferred from the ascending limb to the descending limb
What is the overall effect of the arrangement of the loop of Henle?
Increasing the concentration of mineral ions in the tubule fluid, which has a similar effect upon the concentration of mineral ions in the tissue fluid. This gives the tissue fluid in the medulla a very negative water potential.
What happens as mineral ions enter the descending limb?
The concentration of fluid in the descending limb rises. This means its water potential decreases, and becomes increasingly more negative the deeper the tubule descends into the medulla.
What happens as fluid rises up the ascending limb?
Mineral ions leave the fluid. At the base this movement is by diffusion. Higher up the ascending limb active transport is used to move mineral ions out. The upper portion of the ascending limb is also impermeable to water.
What is the effect of these ionic movements?
Creation of higher water potential in the fluid of the ascending limb. Water potential is decreased in the tissue fluid of the medulla. The water potential of the tissue fluid becomes lower towards the bottom of the loop of Henle.
What happens as fluid passes down the collecting duct?
It passes through tissues with an ever-decreasing water potential. Therefore, there is always a water potential gradient between the fluid in the collecting duct and that in the tissues. This allows water to be moved out of the collecting duct and into the tissue fluid by osmosis.
What is the arrangement of the loop of Henle known as?
A hairpin countercurrent multiplier system. The overall effect of this arrangement is to increase the efficiency of transfer of mineral ions from the ascending limb to the descending limb, in order to create the water potential gradient seen in the medulla.
The collecting duct
The tubule still contains a lot of water and has a high water potential
The collecting duct carries the fluid back down to the pelvis through the medulla
As the tubule fluid passes down the collecting duct, water moves by osmosis from the tubule fluid into the surrounding tissue
It then enters the blood capillaries by osmosis and is carried away
Describe the concentration changes in the tubule fluid
Glucose decreases in concentration as it is selectively reabsorbed from the proximal tubule
Sodium ions diffuse into the descending limb of the loop of Henle, causing the concentration to rise. They are then pumped out of the ascending limb, so the concentration falls.
The urea concentration rises as water is withdrawn from the tubule. Urea is also actively moved into the tubule
Sodium ions are removed from the tubule, but their concentration rises as water is removed from the tubule, and potassium ions increase in concentration as water is removed. Potassium ions are also actively transported into the tubule to be removed in urine.
What is osmoregulation and what does it involve?
The control of water potential in the body. Involves controlling levels of both water and salt. The correct water balance between cells and the surrounding fluids must be maintained to prevent water entering cells and causing lysis or leaving cells and causing crenation.
The mechanism of osmoregulation
The kidneys alter the volume of urine produced by altering the permeability of the collecting ducts. The walls of the collecting ducts can be made more or less permeable according to the needs of the body
if you need to conserve less water (on a cool day or if you have drunk a lot of fluid), the walls of the collecting ducts become less permeable. This means less water is re absorbed and a greater volume of urine is produced.
If you need to conserve more water (on a hot day or when you have drunk very little), the collecting duct walls are made more permeable so more water can be re absorbed into the blood, producing a smaller volume of urine.
Altering the permeability off the collecting duct
cells in collecting duct wall respond to ADH- these cells have membrane bound receptors for ADH
The ADH binds to these receptors and causes a chain of enzyme-controlled reactions inside the cell
The end result of these reactions is to cause vesicles containing aquaporins to fuse with the cell-surface membrane, making the walls more permeable to water
What happens when the level of ADH in the blood rises?
More aquaporins inserted, allowing more water to be absorbed into the blood by osmosis. Less urine produced, urine has a lower water potential.
What happens if the level of ADH in the blood falls?
Cell surface membrane invaginates to create new vesicles that remove water permeable channels from the membrane, making the walls less permeable and less water is re absorbed by osmosis into the blood. More water passes down the collecting duct to form a greater volume of urine with a higher water potential.
What are osmoreceptors?
The hypothalamus contains specialised cells called osmoreceptors. These are the sensory receptors that detect the stimulus- they monitor water potential of the blood. These cells respond to the effects of osmosis. When water potential of the blood is low, the osmoreceptor cells lose water by osmosis and shrink, stimulating neurosecretory cells in the hypothalamus in the process.
Neurosecretory cells and ADH
neurosecretory cells are specialised neurones that produce and release ADH
ADH is manufactured in the cell body in the hypothalamus
ADH moves down the axon to the terminal bulb in the posterior pituitary gland, where it is stored in vesicles
When the neurosecretory cells are stimulated by the osmoreceptors, they carry action potentials down their axons and cause the release of ADH by exocytosis
Where does ADH enter?
Blood capillaries running through the posterior pituitary gland. It is transported around the body and acts on the cells of the collecting ducts. Once the water potential of the blood rises again, less ADH is released. ADH is slowly broken down- its half life is about 20 minutes. Therefore, the ADH present in the blood is broken down so the collecting ducts receive less stimulation.
What happens when the water potential of the blood increases?
detected by osmoreceptors in the hypothalamus
Less ADH released from posterior pituitary
Collecting duct walls less permeable
Less water reabsorbed into blood, more urine produced
Decrease in water potential of blood
What happens when the water potential of the blood decreases?
detected by osmoreceptors in the hypothalamus
More ADH released from posterior pituitary
Collecting duct walls more permeable
More water reabsorbed into the blood, less urine produced
Increase in water potential of the blood
Assessing kidney function
estimating the glomerular filtration rate, and analysing urine for proteins- proteins in urine indicate the filtration mechanism has been damaged
GFR is a measure of how much fluid passes into the nephrons each minute. A normal reading is 90-120 cm3min-1
Figure below 60 indicates chronic kidney disease, below 15 indicates kidney failure
Possible causes of kidney failure
Diabetes mellitus, heart disease, hypertension, infection
Renal dialysis
waste products, excess fluid and mineral ions are removed from the blood by passing it over a partially permeable dialysis membrane that allows the exchange of substances between the blood and dialysis fluid
Dialysis fluid contains the correct concentrations of mineral ions, urea, water and other substances found in blood plasma
Any substances in excess in the blood diffuse across the membrane into the dialysis fluid, and any substances that are too low in concentration diffuse into the blood from the dialysis fluid
Haemodialysis
Blood from an artery or vein is passed into a machine that contains an artificial dialysis membrane shaped to form many artificial capillaries, increasing surface area for exchange. Heparin is added to avoid clotting. The artificial capillaries are surrounded by dialysis fluid, which flows in the opposite direction to the blood. This improves the efficiency of exchange. Any bubbles are removed before the blood is returned to the body via a vein. Haemodialysis is usually performed at a clinic two or three times a week, but patients can learn to do it at home.
Peritoneal dialysis
The dialysis membrane is the body’s own abdominal membrane. A surgeon implants a permanent tube in the abdomen. Dialysis solution is poured through the tube and fills the space between the abdominal wall and organs. After several hours, the solution is drained from the abdomen. Sometimes called ambulatory PD because it can be carried out whilst patient is mobile.
Kidney transplant
While the patient is under anaesthesia, the surgeon implants the new organ into the lower abdomen and attaches it to the blood supply and bladder. Patients are given immunosuppressant drugs to help prevent rejection by the immune system.
Advantages of a kidney transplant
freedom from time-consuming renal dialysis
Feeling physically fitter
Improved quality of life
Improved self image
Disadvantages of a kidney transplant
need to take immunosuppressant drugs
Need for major surgery under general anaesthetic
Need for regular checks for signs of rejection
Side effects of immunosuppressant drugs- fluid retention, high blood pressure, susceptibility to infections
Urine analysis
Urine can be tested for:
glucose for diabetes diagnosis
Alcohol to determine blood alcohol levels
Many recreational drugs
Pregnancy testing- hCG
Anabolic steroids
Pregnancy testing
Urine poured onto test stick
HCG binds to mobile antibodies attached to a blue bead
Mobile antibodies move down test stick
If hCG is present, it binds to fixed antibodies holding the bead in place- a blue line forms
Mobile antibodies with no hCG attached bind to another fixed site to ensure the test is working
Testing for anabolic steroids
Half life of 16 hours, remain in the blood for many days. Urine sample analysis using gas chromatography.
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