Homeostasis

What is Homeostasis?

Homeostasis in mammals is the process of maintaining the internal environment within restricted limits. Multiple physiological control systems are involved to maintain temperature, pH, glucose concentration and water content but they are all examples of negative feedback systems: 

If a factor in the internal environment increases or decreases above or below the ideal level, changes take place to restore the original level. 

A negative feedback control system responds when conditions change from the ideal and returns conditions to the optimum level. Negative feedback is a continuous cycle.

Our body has two main systems which it uses to maintain a constant internal environment:

• Nervous system: This uses action potentials in neurones to transfer electrical signals from the receptors to the brain and spinal cord (co-ordinators) and then to effectors (these can be muscles or glands).

• Endocrine system: This uses hormones which are released from specialised tissues known as glands and travel through the blood stream to various effector organs.

Temperature and pH

Temperature and pH must be maintained to regulate enzyme activity. If body temperature deviates too far from the optimum of 37°C enzyme activity would decrease (if temperature was too low due to low kinetic energy) or enzymes would denature (if temperature is too high). If blood pH deviates from the optimum (7.35 to 7.45) then enzymes would denature due to ionic bonds being disrupted which hold the tertiary structure of the enzyme in place. 

Temperature Control:

The hypothalamus in the brain contains the thermoregulatory centre, it contains receptors sensitive to the temperature of the blood. It also receives nervous impulses from thermoreceptors in the skin and then sends impulses along motor neurones to various effectors:

Too Hot	Too Cold
Sweat glands in the skin release more sweat. The sweat evaporates, transferring heat energy from the skin to the environment.	Skeletal muscles contract rapidly (shivering). These contractions need energy from respiration, and some of this energy is also released as heat.
Blood vessels dilate - allowing more blood to flow through skin capillaries, and more heat to be lost  This is called vasodilation.	Blood vessels constrict – which allows less blood to flow through skin capillaries and conserve the core body temperature.  This is called vasoconstriction.
If we are too hot nerve impulses are sent to the hair erector muscles in the skin which relax. This causes the skin hairs to lie flat. This is called pilorelaxation.	If we are too cold nerve impulses are sent to the hair erector muscles in the skin which contract. This raises the skin hairs and traps a layer of insulating air next to the skin.  This is called piloerection.

Behavioural temperature adaptations:

 If animals get too hot or cold they can also change their behaviour in response to a change in conditions to help regulate their temperature. 

E.g – basking in the sun, cooling off with water, seeking shade, huddling for warmth, being active or reducing activity. 

Some organisms can increase or reduce their surface area to increase or decrease heat loss through conduction. 

Blood Glucose Concentration is also controlled through negative feedback:

Glucose is constantly needed in cells to produce ATP and provide energy, and it also contributes to the water potential of blood and body fluids outside of cells. 

Blood plasma is 90-92% water with dissolved solutes including glucose, blood glucose concentration must therefore be controlled to maintain the water potential of blood. Any deviation in the water potential of blood will affect the metabolism of cells, as well as causing cells to gain or lose water and so vary in size due to osmosis. 

Blood glucose levels are maintained within the optimum (4-5g in the blood) by an endocrine control system which uses negative feedback. The hormones insulin and glucagon as well as glands in the liver and the pancreas are responsible for maintaining the feedback loop. 

Blood glucose concentration

Blood glucose concentration should stay between 4-8mmol dm-3 of blood. If the concentration is too low cells may not have enough glucose for respiration and may not function normally – brain cells are especially sensitive to this. If blood glucose levels are too high, it can disrupt the water potential of blood and cause disruption as water will start to move in and out of cells – including red blood cells! In patients with diabetes a very high or low concentration of glucose can cause death. 

Blood glucose concentration increases in the body when:

• Eating sugary foods

• Eating food rich in Carbohydrates- Carbohydrates are broken down into monosaccharides in the small intestine and absorbed into the blood

• Glycogen stores in the liver are broken down to release glucose, glucose is then released into the bloodstream (glycogenolysis).

• When other substances are converted into glucose e.g lactate (lactic acid produce in muscles through anaerobic respiration), amino acids, glycerol, fatty acids (gluconeogenesis). This also happens in the liver. Glucose is produced from amino acids and glycerol.

Blood glucose concentration decreases in the body when: 

• During intense exercise – increased levels of respiration in muscles reduces blood glucose levels as uptake into muscles increases, energy is needed for muscle contraction. 

• Glucose used up in respiration- being constantly taken out of the blood for respiration.

• If glucose levels are too high the liver removes glucose from the blood and converts it into glycogen in the liver- takes place after meals to store the glucose produced by digestion (glycogenesis). 

• Drinking alcohol can prevent the liver from producing glucose so can cause a decrease in blood sugar levels. 

Blood glucose concentration is controlled by an endocrine system:

Receptors: located in the islets of Langerhans (endocrine tissue) in the pancreas. 

Signals: The hormones insulin and glucagon – both secreted by the pancreas

Effectors: liver, muscle and fat cells are the target cells of the hormones, they have specific receptors on their membrane. They act as effectors in response to them. 

The pancreas:

Endocrine glands are the glands that secrete hormones without ducts, while exocrine glands secrete hormones through ducts. The pancreas contains both exocrine and endocrine tissue, the exocrine tissue secretes digestive enzymes into the bile duct. The endocrine tissue (the islets of Langerhans) secretes hormones. The islets of Langerhans contain two cell types:

• α cells that secrete the hormone glucagon

• β cells that secrete the hormone insulin

Blood glucose regulation

• The concentration of glucose in the blood must be kept at a constant level

• Glucose is used by cells to produce ATP via respiration.

• If the blood glucose concentration falls, then the rate of respiration may also fall.

• If the blood glucose concentration gets too high, it lowers the water potential of the blood. This causes water to move out of cells into the blood by osmosis from a less negative to a more negative water potential.

Normal Blood Glucose Concentration

90 mgcm-3

Blood glucose concentration increases

• The increase is detected by beta cells in the pancreas

• Beta cells secrete insulin into the bloodstream

• Insulin has three effects:

• 1- Binds to insulin receptors on the cell surface membrane. This triggers vesicles carrying glucose transport protein channels to fuse with the cell membrane. The glucose transport protein channels are now inserted into the cell surface membrane. So, more glucose molecules can now move into the cell by facilitated diffusion

• 2- Insulin triggers the rate of respiration to increase- will require more glucose

• 3- Insulin triggers glycogenesis and lipid synthesis from glucose (Glycogenesis= glucose is converted into glycogen in the liver and muscle cells)

• Once blood glucose conc reduces back to normal levels, the beta cells detect this and reduces the amount of insulin secreted (Negative feedback).

Blood Glucose concentration decreases

• Blood glucose decreases- this is detected by alpha cells in the pancreas

• The alpha cells secrete glucagon into the bloodstream

• Glucagon receptors are found on the cell surface membrane of liver cells

• Effects of Glucagon:

• 1- Liver cells are triggered to break down glycogen into glucose (Glycogenolysis- glycogen is broken down to glucose) in the liver cells. Glucose is then released into the bloodstream.

• 2- Liver cells are triggered to carry out gluconeogenesis (to produce glucose from amino acids and glycerol). Glucose is released into the bloodstream.

• 3- Glucagon reduces the amount of glucose that liver cells absorb from the blood

• Once the blood glucose concentration increases, this is detected by alpha cells in the pancreas. Alpha cells reduce the amount of glucagon secreted (Negative feedback).

Adrenaline

• Causes blood glucose concentration to increase

• Adrenaline is secreted by the adrenal glands during during stressful situations (fight or flight)

• Adrenaline triggers liver cells to convert glycogen into glucose. Glucose is then released into the bloodstream.

• The glucose can then be used as a source of energy for muscle contraction during fight or flight.

The Kidneys

The kidneys form the urinary system with the bladder and have two roles in the body:

• Osmoregulation – maintaining the water potential of blood by removing excess water or retaining water.

• Excretion – removing nitrogenous waste (excess protein) in the form of urea from the blood. 

There are two kidneys, each receives blood from the renal artery. Kidneys act like filters, removing urea from the blood and diluting it with water to form urine. Urine is then sent to the bladder for storage via the ureter. Once the bladder fills the urine passes out through the urethra.

The kidney reabsorbs important amino acids, salts and glucose that it filters out of the blood initially so that they are not lost in urine. The amount of water in the urine is adjusted to maintain the water potential of the blood. 

Kidney Structure

Nephron – fine tube structures which carry out filtration and reabsorption. There are roughly one million nephrons in each kidney (200,000 – 2.5 million).

The Cortex – the outer layer jammed pack full of the filtration parts of the nephrons. Filters the blood.

Medulla – the inner layer which contains the tubes carrying filtered wastes to the centre (pelvis) of the kidney. Contains the loop of Henle and the collecting duct parts of the nephrons. 

Renal Pelvis – Where all the collecting ducts come together and connect to the ureter. 

Ureter – transports urine to the bladder to be excreted. 

Ultrafiltration

The first function of the nephron is to filter the blood. This takes place at a structure called the glomerulus: A many-branched knot of capillaries from which fluid is forced out of the blood using blood pressure. 

Blood enters the glomerulus from the renal artery through the afferent arteriole, the blood flows through the knot of capillaries and leaves through the efferent arteriole which has a narrower lumen than the afferent arteriole. This creates a high hydrostatic pressure which forces plasma from the blood through the walls of the capillaries into a filter called the Bowman’s capsule. 

Small molecules can leave including glucose, amino acids, hormones, urea, water, and ions but large proteins and red blood cells are too big to pass through the gaps in the walls of the capillary endothelium called fenestrations. 

The plasma then passes through a filter into the lumen of the Bowman’s capsule which is a cup shaped sack around the glomerulus. The filter is made up of the basement membrane and specialised Bowman’s capsule epithelial cells called podocytes. The foot processes known as pedicels that extend from the podocytes wrap themselves around the capillaries of the glomerulus to form filtration slits. The pedicels increase the surface area of the cells enabling efficient ultrafiltration. Podocytes also secrete and maintain the basement membrane which is a mesh like layer of proteins. This filtration system prevents large or charged molecules from entering the glomerular filtrate which then flows through the rest of the nephron. 

Selective Reabsorption

The rest of the nephron is responsible for making sure necessary, useful molecules remain in the body, firstly this is done through selective reabsorption then through the reabsorption of water. The glomerular filtrate flows from the Bowman’s capsule into the proximal convoluted tubule (PCT) where approximately 85% of the filtrate is reabsorbed into the blood including: 

• All of the glucose – needed for respiration

• All of the amino acids – needed for building proteins

• Some inorganic salts – often ones low in concentration in the blood, not high in diet

• Most of the water moves back into the blood by osmosis

The cells lining the PCT are specialised to maximise reabsorption: 

• Folded membrane to give large surface area so lots of reabsorption can occur simultaneously

• Lots of membrane proteins for facilitated diffusion of glucose and amino acids via co-transport with sodium

• Lots of ribosomes to make those membrane proteins

• Lots of mitochondria to provide the ATP for protein synthesis and active transport which could be used to reabsorb the molecules

Osmoregulation and ADH

Filtration is one role of the kidneys, the other is osmoregulation or control of water potential of the blood. In order to do this the kidneys have to control how much water is reabsorbed into the blood and how much is removed in urine.

Loop of Henle

The loop of Henle is where this process starts, its function is to create a low water potential in the medulla of the kidney. 

So far the glomerulus and PCT have been situated in the cortex of the kidney but the loop of Henle consists of a descending limb into the medulla and an ascending limb back out to the cortex​. 

This allows salts (sodium and chloride ions) to be transferred from the ascending limb to the descending limb​. The overall effect is to increase the concentration of salts in the filtrate so that they diffuse out from the ascending limb into the surrounding medulla tissue, giving a low (very negative) water potential.

Remember – the nephron is surrounded by a network of capillaries; water is therefore reabsorbed into the blood not just out into the tissue fluid. 

 1 – As fluid is moving up the ascending limb sodium and other ions are actively transported out of the filtrate into the tissue fluid. The loss of these ions causes the filtrate to become less concentrated (higher water potential)

2 – The sodium ions lower the water potential of the surrounding medulla tissue; the water potential of the medulla becomes more negative towards the base of the loop of Henle. Water does not follow the ions due to osmosis because the membrane of the ascending limb is impermeable to water.

3 – The descending limb is permeable to water, so water moves out of the filtrate here by osmosis into blood capillaries because the ions have made the surrounding tissue have a very low water potential. This concentrates the filtrate lowering the water potential. 

The loop of Henle uses a hairpin countercurrent multiplier because it allows the concentration of the filtrate to increase (by reabsorbing water) and the concentration of the external tissue to increase (which helps to remove the water) at the same time. This ultimately allows the nephron to reabsorb more water and concentrate the urine while at the same time using as little energy as possible.

DCT and Collecting Duct

Filtrate moving from the top of the ascending limb of the loop of Henle into the distal convoluted tubule and the collecting duct still has a high water potential. The collecting duct is the last chance for the body to keep hold of any water that’s been filtered out of the blood. The water potential gradient set up by the loop of Henle allows water to be absorbed along the whole length of the collecting duct

The permeability of the membrane of both of these sections of the nephron is controlled by the hormone ADH (antidiuretic hormone). Any change in blood water potential is detected by osmoreceptors in the hypothalamus. If the hypothalamus detects that blood water potential is too low it stimulates the posterior pituitary gland to secrete more ADH. 

Too little water in blood  (low water potential)	Too much water in blood  (high water potential)
Low concentration of water in the blood is detected by osmoreceptors in the hypothalamus	High concentration of water in the blood is detected by osmoreceptors in the hypothalamus
Pituitary gland is stimulated to release more ADH	Pituitary gland is stimulated to release less ADH
ADH travels in the blood to the kidney	ADH travels in the blood to the kidney
ADH causes the collecting ducts to become more permeable to water	ADH causes the collecting ducts to become less permeable to water
This means more water is reabsorbed back into the blood	This means less water is reabsorbed back into the blood
Volume of urine decreases, and concentration increases	Volume of urine increases, and concentration decreases

How ADH works

Cells in the wall of the collecting duct have receptors for ADH​ on their plasma membrane, they also contain vesicles with aquaporins (water protein channels). 

ADH binds to these receptors and causes a chain of enzyme controlled reactions inside the cell​ using the secondary messenger model. The cascade causes the vesicles containing the aquaporins to move and fuse with the membrane. This makes the membrane of cells lining the collecting duct more permeable to water​. 

More ADH in the blood means more aquaporins are inserted allowing more water to be reabsorbed, and less, more concentrated urine with a lower (more negative) water potential

Summary of blood glucose control

Process	Converts	Activated by	Inhibited by	Happens in
Glycogenesis	Glucose to glycogen	Insulin from pancreas	Adrenaline from adrenal gland	Liver
Glycogenolysis	Glycogen to glucose	Glucagon from pancreas and Adrenaline from adrenal glands		Liver and Muscles
Gluconeogenesis	Glycerol/amino acids to glucose	Glucagon		Liver

Diabetes

Diabetes is a condition where blood glucose concentration cannot be controlled properly. After eating blood glucose concentration does not reduce as it should as glucose is not being absorbed. A normal blood glucose concentration of above 7.8mM is considered high enough to be diabetes.

There are two types:

	Type 1	Type 2
Caused by	The immune system attacks β cells in the islets of Langerhans. Not sure why this happens could be genetic cause or the result of a viral infection	β cells in the islets of Langerhans do not produce enough insulin or the body’s cells do not respond properly to insulin. This can be caused by fat around the organs. Effects people with poor diet, lack of exercise but also older people or people with family history are at risk
Effect	Pancreas no longer secretes insulin	Insulin receptors on target cells do not work properly so cells do not take up enough glucose.
Consequence	After eating blood sugar levels can become very high – hyperglycaemia. The kidneys cannot reabsorb all the glucose. Could lead to coma and death if it gets too high!	Blood glucose concentration is generally higher than normal.
Symptoms	glucose in urine increased thirst and a dry mouth needing to urinate frequently tiredness unintentional weight loss	urinating more than usual, particularly at night feeling thirsty all the time feeling very tired losing weight without trying to cuts or wounds taking longer to heal
Treatment	Insulin therapy – injecting insulin regularly throughout the day after eating. It needs to be carefully controlled as injecting too much could cause a dangerous drop in blood glucose – hypoglycaemia. Regular, healthy diet helps to control levels.  Long term stem cell treatment or a pancreas transplant	Eating a balanced diet and exercise regime. Glucose-lowering medication can be taken if these do not help control it. Taking insulin or having a pancreas transplant would not be effective as cells do not respond properly to insulin.

Type 2 Diabetes Causes and Responses

Type II diabetes prevalence is increasing in the UK population as it is linked to increasing levels of obesity. This is a direct result of an increase in unhealthy diets along with a reduction in physical activity. Type II diabetes can cause other health problems including increased risk of heart disease, stroke, vision loss and kidney failure. This puts a strain on the NHS so health advisors want to try and increase awareness and reduce obesity levels through education, but some people believe that the food industry also has a role to play. 

 

Health Advisors Responses	Food Industry Responses
Recommend that people’s diet is low in fat, sugar, and salt but contains lots of grains, fruit, and vegetables. And promote regular exercise.	Make products healthier by using sugar alternatives to sweeten food and drink and reducing sugar, fat, and salt content. However, there is some evidence to suggest that artificial sweeteners are linked to weight gain.
Campaigns including the NHS ‘Change4Life’ to educate people about how having a healthy lifestyle can reduce their risk of developing conditions including Type II diabetes.	There is pressure to increase profits so they are reluctant to spend money on developing healthier alternatives if they will be less popular and make less money.
Challenging the food industry to reduce advertising of junk food to children and make labelling clearer so that people can make healthier choices.	The food industry will only change in the long term if public opinion and habits towards healthy eating change.

Testing for glucose in urine

If it is suspected that a person has diabetes a doctor may request a sample of their urine be tested for glucose. Normally the concentration of glucose in urine should be very low (0-0.8mM). Along with other symptoms if the value is higher than this could mean the patient has diabetes – a blood test would then be used to confirm this as it could also be caused by high blood pressure or kidney failure. We can test urine for the presence of glucose using Benedict’s reagent. 

There are two types of Benedict’s reagent:

Qualitative	Contains potassium thiocyanate	Produces a range of coloured precipitates when boiled from green to brick red in the presence of reducing sugar.
Quantitative	Contains copper sulphate	Does not give a red precipitate on boiling. The amount of reducing sugar present is measured by the disappearance of the blue colour of copper sulphate.

Quantitative Benedict’s reagent can be used to test a range of known concentrations of glucose and a colorimeter used to measure the absorbance of each sample. This is used to create a calibration curve (straight lines are still curves!)

The higher the glucose concentration the paler the solution so the lower the absorbance reading. 

Once this has been done, samples of unknown glucose concentration can be tested with Benedict’s and the absorbance measured. The calibration curve can then be used to estimate the concentration of glucose in the unknown sample based on its absorbance reading.