HOMEOSTASIS

Homeostasis – the maintenance of a constant internal environment within restricted limits in organisms. This involves volume, chemical make-up and other features of the blood and tissue fluid (bathe the cells, supply nutrients and remove wastes). It ensures that the cells are in an environment that meets their requirements and allow them to function normally even if there are external changes. This gives an organism a degree of independence. There continuous fluctuations brought about by variations in internal and external conditions, like changes in temperature, pH and water potential, but occur around an optimum point. Homeostasis is the ability to return to the optimum point and so maintain organisms in a balanced equilibrium.

Homeostasis is important for the following reasons, amongst others:- Enzymes and proteins are sensitive to pH and temperature, changes to them could decrease

their function or denaturing them. - Changes to water potential could cause cells to shrink or expand, maybe even burst (lyses)

due to water entering or leaving by osmosis. This prevents the cell to operate normally. - Organisms with the ability to maintain a constant internal temperature are more

independent of changes in the external environment. They can have a wider geographical ranger and so greater chance of finding food, shelter, etc.

Control mechanisms:- Optimum point – the point at which the system operates best. This is monitored by…- Receptor – detects any deviation from the optimum point (detects a stimulus) and informs

the...- Coordinator – which coordinates information from receptors and sends instruction to an

appropriate…- Effector – often a muscle or a gland, which brings about the changes to return to optimum

point. This return to normality creates a…- Feedback mechanism, by which a receptor responds to a stimulus created by the change to

the system brought about by the effector.

It is important that when an effector has corrected any deviation and returned the system to the optimum point, this information is fed back to the receptor. If this is not done, the receptor will continue to stimulate the effector leading to over-correction.

Most systems use negative feedback. Negative feedback – when the change produced by the control system leads to a change in the stimulus detected by the receptor and turns the system off, returning the system to its optimum level and preventing overshoot. Example of this is control of blood glucose. Having two receptors that work antagonistically to each other gives a greater degree of homeostatic control. Positive feedback – a deviation from an optimum causes changes that results in an even greater deviation from the normal. The corrective measure is not turned off. An example of this can be seen in the neurones when a stimulus leads to small influx of Na2+, which causes a further increase in Na2+. It also occurs during certain diseases, like typhoid fever, where there is breakdown of temperature regulation leading to rise in body temperature leading to hyperthermia.

Control systems normally have many receptors and effectors, giving separate mechanisms to produce movement towards an optimum. This allows greater degree of control of a particular factor being regulated.

The information provided form the receptor is analysed by the coordinator before the action is taken place. For example, the skin receptors may be saying it is cold and that body temperature should be raised. But information from regions in hypothalamus in the brain may indicate that blood temperature is above normal. By analysing the information from all detectors the brain can decide the best action, in this example not to raise body temperature.

Hypothalamus – region of the brain that is responsible for producing hormones to regulate temperature, thirst, hunger, sleep, mood, sex drive, and other functions.

Endotherms – animals that get their heat from their own metabolic activities; an animal that is dependent on or capable of internally generating heat. Ectotherms – animals who obtain their heat from their environment; an animal that is dependent on external sources of body heat. Ectotherms control their temperature by their behaviour. Reptiles control their temperature by:

- Exposing themselves to the Sun – orientate that the maximum area of their body is exposed. - Taking shelter , so they would not over-heat during the hottest peaks. In the night they

retreat into burrows to reduce heat loss when the external temperature is low. - Gaining warmth from the ground , by pressing against it.

Endotherms regulate their temperature by physiological mechanisms:In cold climates, mammals and bird evolved features like small surface area to volume ratio, smaller extremities and thick fur, feather or fat layers to insulate the body. More rapid mechanisms:

- Vasoconstriction – when the diameter of arterioles near the surface of the skin becomes smaller. This reduces volume of blood reaching the skin surface through capillaries and the blood that enters the skin is insulated by layer of fat. Loses little heat to the environment

- Shivering – muscles undergo/experience involuntary rhythmic contractions to produce metabolic heat.

- Raising of hair – caused by hair erector muscles contract, which causes a thicker layer of air around the skin, insulating and conserving mammals.

- Increased metabolic rate – increase of respiration by hormones. - Decrease in sweating - Behaviour - sheltering from wing, huddling together, expose oneself to the sun

In warm climates, rapid responses to lose heat in the environment:- Vasodilation – when diameter of the arterioles near the surface of skin increases to allow

more warm blood to pass close to the skin surface. - Increased sweating – energy is needed to heat up water. The high latent heat of

vaporisation of water makes sweating an efficient way of losing heat. Furry animals cool by panting, water evaporating from mouth and tongue.

- Lowering of body hair – hair erector muscles relax and causes the hair to flatten against the body. This reduces the thickness of the insulating layer.

- Behaviour – avoiding heat during the day by sheltering in burrows and seeking shade.

Hormones similar characteristics:- Produced in glands (endocrine glands) that secrete hormones directly into the blood- Carried in the blood plasma to target cells (cells they act on – have specific receptors on

their cell-surface membrane that is complementary to the hormone. - Effective in low concentrations but have widespread and long-lasting effects.

Second messenger model – hormone mechanism that uses two hormones in regulation of something, for example blood glucose contraction.

REGULATION OF BLOOD GLUCOSE

The system have antagonistic hormones working against each other, e.g. insulin and glucagon Uses negative feedback. Concentration of glucose fluctuates around an optimum point.

Glossary of regulation of blood sugar by the liver:- Glucose – hexose monosaccharide, used for respiration - Glycogen – a polysaccharide made of isomer of α glucose, highly branched- Islets of Langerhans – hormone producing cells in the pancreas- α cells – produce hormone glucagon- β cells – produce hormone insulin - glucagon – hormone that increases glucose concentration - insulin – hormone that lower glucose concentration; globular protein of 51 amino acids - glycogenesis – conversion of glucose to glycogen - glycogenolysis – breakdown of glycogen to glucose- gluconeogenesis – production of glucose from sources non-carbohydrate, such as glycerol

and amino acids - glycerol – part of the triglycerides and phospholipids

- gluco/glycol – glucose - neo – new - lysis – splitting - genesis – birth/origin

Role of pancreas:Pancreas – large, pale-coloured gland found in upper abdomen and produced enzymes, such as protease, amylase and lipase, for digestion and hormone, insulin and glucagon, for regulating blood glucose concentration. The cells that produce the hormones is known as islets of Langerhans. They include:

- Alpha cells – larger and produce glucagon. - Beta cells – smaller and produce insulin.

Role of liver:Liver – located below the diaphragm and is made of cells hepatocytes. It has many roles including regulating blood glucose concentration. Glycogenesis, glycogenolysis and gluconeogenesis and processes that take place in the liver. Liver can store 75-100g of glycogen which is sufficient amount to maintain human’s blood glucose for about 12 hours at rest, in absence of other sources.

Importance of maintain blood glucose concentration- glucose is respiratory substance of cells, this is sensitive to brain cells who can only respire

on glucose - Maintaining water potential of the cells – cells could either gain or lose water by osmosis

which can it to shrivel or burst. This is particularly sensitive to brain cells.

Normal concentration of blood is 5mmmol dm-3. Blood glucose comes from three sources:- Diet – absorbed glucose from hydrolysis/digestion of other carbohydrates like starch,

maltose, lactose and sucrose.

- From glycogenolysis- From gluconeogenesis

β cells’s receptors detect the rise of blood glucose concentration (stimuli)

They respond by secreting insulin directly into blood plasma.

Insulin binds to glycoprotein receptors (which almost all body cells have, red blood cells do not have).

The α cells detect fall in blood glucose concentration

(stimuli)

They respond by secretin glucagon into blood plasma

Other hormonesThere are at least four other hormones apart from glucagon that can increase blood sugar concentration, one of them being adrenaline. At times of excitement or stress, adrenaline is produced by the adrenal glands (lie above the kidneys). It raises concentration by:

- Attaching to protein receptors on cell-surface membrane of target cells- Activate enzymes that perform glycogenesis

Adrenaline involved mechanism:- Adrenaline binds to a transmembrane protein receptor within the cell-surface membrane of

liver cell. - The binding of adrenaline causes the protein to change shape on the inside of the

membrane. - The change in shape leads to activation of an enzyme, adenyl cyclase, which converts ATP to

cyclic AMP (cAMP). - cAMP acts as a second messenger and binds to protein kinase enzyme, activating it by

changing its shape.

Change tertiary structure of glucose transport carrier proteins, which causes their overall shape to change to open and allow more glucose to enter the cell by facilitated diffusion.

Increase number of carrier proteins responsible for glucose transport in cells-surface membrane by making the vesicles containing them fuse with the membrane

Activate enzymes to perform glycogenesis and glucose to fat. Increasing rate of

absorption of glucose into cells, in particular muscle cells.

Increasing rate of respiration Increasing rate of

glycogenesis and rate of conversion glucose into fat

Attach to specific protein receptors on cell-surface membrane

Activate enzymes to perform glycogenesis

Activate enzymes to perform gluconeogenesis from amino acids and glycerol

Increase concentration of blood glucose

- Kinase protein catalyses the glycogenolysis, the glucose produced moves into the blood by facilitated diffusion through channel proteins.

Diabetes – type of disease that in which a person is unable to metabolise carbohydrate properly, in particular glucose. One form of it is diabetes mellitus. It is a metabolic disorder caused by an inability to control blood glucose concentration due to a lack of the hormone insulin or loss of responsiveness to insulin.

There are two forms of diabetes:Type I (insulin dependent) Type II (insulin independent)Due to the body being unable to produce insulin. It may be the result of an autoimmune response when body immune system attack its own cells.

Normally due to glycoprotein receptors on body cells being lost or losing their responsiveness to insulin. It also may be due to an inadequate supply of insulin from pancreas.

Develops quickly Develops slowlyUsually develops in childhood It usually develops in people of around 40 years

of age. Though due to obesity and poor diet type Ii diabetes can occur as young as adolescentsSymptoms are usually less severe and may go unnoticedAbout 90% of people have with diabetes have type II

Signs of diabetes: - High blood glucose concentration- Presence of glucose in urine- Need to urinate excessively- Genital itching or regular episodes of

thrush

- Weight loss- Blurred vision

Symptoms of diabetes: - Tiredness - Increased thirst and hunger

Diabetes can be treated successfully, though no cure is not yet found:- Type I diabetes – injections of insulin, the does of insulin must be matched exactlu to the

glucose intake. If a person with diabetes takes too much insulin, they will experience low blood glucose concentration that can result in unconsciousness. To make sure the correct does is taken, blood glucose concentration is monitored usuing biosensors.

- Type II diabetes – controlled by regulating the inatke of carbodydrate in diet and matching this to the amount of exersize taken. In some cases this may be supplemented by enjoection of insulin or use drugs that stimulate insulin production or slow down rate at which the body absrobs glucose from the intestine.

The table above shows daily balance between loss and gain of salts and water from a typical human. In blood optimum concentration of water and salts is mantained to keep water potential of blood plasma and tissue fluid constant. Osmoregulation – homeostatic control of water potential of the blood. It is carried out the neuphron in the kidney. Neuphron – narrow tube up to 14 mm long, closed at one end, with two twisted regions seperated by a long hairpin loop. Filtering structure in the kidneys. It removes excess water, wastes and other substances from your blood, and returns substances like sodium, potassium or phosphorus whenever any of these substances run low in your body. Kidney – an organ that removes waste products and drugs from the body, balance body’s fluids, release hormones to regulate blood pressure, produce vitamin D to promote strong, healthy bonds and control production of red blood cells. They are found at the back of the abdominal cavity, one on each side of the spinal chord. http://www.kidneyhealthcare.com/2010/12/nephron-structure-function-nephron.html https://www.kidney.org/kidneydisease/howkidneyswrk

Structure of mammalian kidney- Fibrous capsule – outer membrane that protect the kidney- Cortex – a lighter coloured outer region, consists of Bownman’s capsules, convoluted

tubules and blood vessels. - Medulla – darker coloured inner region, consists of loops of Henle, collecting ducts and

blood vessels. - Renal pelvis – funnel-shaped cavity that collects urine into the ureter- Ureter – tupe that carries urine to the bladder- Renal artery – supplies kidney with blood from the heart via aorta- Renal vein – remainds blood to the heart via the vena cava

In each kidney there are around one million nephrons.

Structure of the nephron- Bowman’s capsule – closed end at the start of nephron; cup-shaped and surrounds

glomerulus. The inner layer of the capsule consists of specialised cells, podocytes. - Proximal convoluted tubules – series of loops surrounds by blood capillaries; its walls are

made of epithelial cells with microvilli.

- Loop of Henle – long, hairpin loop that extends from the cortex into the medulla of the kidney and back again. Surrounded by blood capillaries. The loop can be divided further into two parts, descending and ascending loop.

- Distal convoluted tubule – series of loops that surrounded by blood capillaries. Its walls are made of epithelial cells, but it is surrounded by fewer capillaries than the proximal tubule.

- Collecting duct – a tube into which a number of distal convoluted tubules from a number of nephron empty. It is lined by epithelial cells and becomes increasingly wide as it empties into the pelvis of the kidney.

Associating blood vessels:- Afferent arteriole – vessel that arises from renal artery and supplies nephron with blood. In

the capsule forms glomerulus. - Efferent arteriole – vessel that leaves the capsule, has smaller diameter and so has higher

blood pressure. - Glomerulus – many-branched knot of capillaries from which fluid is forced out of the blood. - Blood capillaries – concentrated network of capillaries that surrounds the proximal

convoluted tubule, the loop of Hele and distal convoluted tubule. They reabsorb the mineral salts, glucose and water. The capillaries merge into venules (tiny veins) that merge together to form renal vein.

Dissection guide for kidney:http://ftp.collin.edu/lcorrea/Department%20of%20Biology%20Page/Anatomy%20&%20Physiology/A&P%20II%20Urinary%20System/Kidney%20Dissection%20Guide.pdf

One important function of the kidney is to maintain the water potential of plasma and so tissue fluid – osmoregulation.

The nephron carries out its role of osmoregulation in stages:1) Formation of glomerular filtrate by ultrafiltration

Blood enters the kidney through the renal artery, branching into one million afferent arterioles, each of them entering the Bowman’s capsule of a nephron. In the capsule it becomes a glomerulus, the capillaries later megre to form efferent arteriole which sub-divides into capillaries and wind around the various tubules of the nephron before combining to form the renal vein. The walls of glomerular capillaries are epithelial cells with pores between them. Due to lower diameter of the efferent arteriole, there is a build-up of hydrostatic pressure within the glomerulus. Due to this water, glucose and mineral ions are squeezed out of the capillary to form the glomerular filtrate. Blood cells and proteins are too large so remain in the capillary. The movement is resisted by:

- Capillary epithelial cells- Connective tissue and epithelial cells of blood capillaries- Epithelial cells of capsule- Hydrostatic pressure of fluid in capsule space- Low eater potential of the blood on glomerulus.

This would prevent the filtrate to leave the glomerular capillaries. However, there are modifications to reduce this barrier:

- Inner layer of renal capsule is made of podocytes, which have spaces between them which allow filtrate to pass beneath them and through gaps between the branches.

- The endothelium of glomerular capillaries has spaces up to 100nm wide between its cells, allowing fluid pass between them rather than through cells.

Due to this, the hydrostatic pressure of bloom is sufficient to overcome the resistance and filtrate passes from the glomerulus into renal capsule. The filtrate does not contain cells or plasma proteins because they are too large to pass through the connective tissue.

2) Reabsorption of glucose and water by proximal convoluted tubule Almost 85% of filtrate is reabsorbed back into the blood. Ultrafiltration operates by size and most of 125cm3 of filtrate is extremely useful for the body, for is reabsorbed. Some, however are wastes like urea. Proximal convoluted tubules are adapted to reabsorb substances into the blood by having epithelial cells that have:

- Microvilli – provides larger surface area- Infoldings at their bases give large surface are to transfer reabsorbed substances into

capillaries- High density of mitochondria to provide ATP for active transport

Active transport process:- Na+ are actively transported by the cells lining of proximal convoluted tubule into blood

capillaries, creating a diffusion gradient. - Na+ diffuse does a concentration gradient from the lumen of the proximal convoluted tubule

by facilitated diffusion by co-transport carrier proteins. These proteins are specific to other types of molecules, for example glucose, amino acids or chloride ions.

- Majority of the molecules that have been co-transported into the cell is reabsorbed by the blood along with water by diffusion.

About 180 dm3 enters the nephrons each day. About 1 dm3 leaves the body as urine. 85% of reabsorption of later occurs in proximal convoluted tubule. The remainder is reabsorbed from collecting duct.

3) Maintenance of a gradient of sodium ions in the medulla by the loop of Henle The loop of Henle is responsible for water being reabsorbed from the collecting duct, concentrating the urine so it has lower water potential than the blood.

The loop of Henle has two regions:- Descending limb – narrow, thin walls which are highly permeable to water- Ascending limb – wider, thick walls which are impermeable to water.

Loop of Henle acts as a counter-current multiplier. The process:

- Na+ are actively transported out of the ascending limb (using ATP provided by many mitochondria in the cells of ascending limb) which creates a low water potential (high ion concentration in the interstitial region (region of medulla between two limbs). Water cannot pass out by osmosis from the ascending limb as it is impermeable to water. No movement of water, and if it is, very little.

- In descending limb is very permeable to water so by osmosis it moves into interstitial space. This water enters blood capillaries and carried away.

- The filtrate in this way lose water, its lowest water potential at tip of hairpin. Here Na+ diffuse out of the filtrate. They are actively pumped out of the filtrate as it moves up the ascending limb. The filtrate gains higher water potential.

http://www.news-medical.net/health/The-Loop-of-Henle.aspx

4) Reabsorption of water by the distal convoluted tubule and collecting ducts - In interstitial space between ascending limb and collecting duct a gradient of water

potential, lower being in the medulla. - Collecting duct is permeable to water and so water moves out of by osmosis as filtrate

moves down it. - The water potential is always higher in the duct than in the interstitial space, so water

continuously moves out while filtrate moves down the collecting duct. The urine leaves the collecting duct on its way to balder, it has a lower water potential than the blood.

Water moves out by special channel proteins that are specific to water – aquaporins. Antidiuret hormone (ADH) – alters number of these channels and so control water loss.

Main role of convoluted tubule is to make final adjustments to the water and salts that are reabsorbed and control the pH of blood by being selective which ions to reabsorb. This is done by controlling the permeability under influence of various hormones. The cells on the walls of the convoluted tubule have microvilli and many mitochondria that allow them to reabsorb material rapidly from filtrate by active transport.

Counter-current system make sure that there is gradient continuously, so water would continuously flow out of distal convoluted tubule and collecting duct, no matter of the water potential of filtrate at this point. If the currents were in the same direction (parallel) less of water would enter the blood.

Regulation of water potential of the bloodWater potential of the blood depends on the concentration of solutes like glucose, proteins, sodium chloride and other mineral ions, and volume of water in the body. A rise in solute (which lowers water potential) can be caused by:

- Too little water being consumed- Lots of sweating - Large amount of ions is taken in

The body uses hormones that acts on distal convoluted tubule and collecting duct for osmoregulation in the blood.

Process:- Cells have osmoreceptors in the hypothalamus of the brain which detect fall in water

potential. It is believed due to the receptors loosing water by osmosis to the blood. The osmoreceptor cells would shrink.

- This change causes hypothalamus to produce a hormone, antidiuretic hormone (ADH). - ADH passes to posterior pituitary gland and secreted into capillaries.- ADH by blood enters the kidney - Specific protein receptors on the cell-surface membranes bind to ADH molecules, which are

on the cell-surface membrane of the cells that make up walls of distal convoluted tubule and collecting duct, leading to activation of an enzyme phosphorylase.

- Phosphorylase causes vesicles within the cell that contain pieces of plasma membrane with numerous aquaporins, to move to and fuse with its cell-surface membrane

- Therefore ADH increases the permeability to urea of collecting duct, so passes out, which further lowers the water potential of the fluid around the duct.

- The combine effect is that more water leaves the collecting by osmosis, down a water potential gradient, and re-enters the blood.

- This would not increase on its own the water potential of the blood. Osmoreceptors also send nerve impulses to the thirst centre of the brain to encourage the individual to find and drink more water.

- The osmoreceptors in the hypothalamus detect the rise in water potential and send fewer impulses to pituitary gland. The gland therefore would reduce the release of ADH and so permeability of collecting ducts to water and urea would revert to its former state.

A fall in solute would rise the water potential, can be caused by:- Large volumes of water being consumed- Salts used in metabolism or excreted and not replaced in the diet.

Process of response: - Osmoreceptors detect rise in water potential. - They increase the frequency of nerve impulses to the pituitary gland to reduce the release of

ADH. - Less ADH, decrease in permeability of collecting ducts to water and urea. - Less water is reabsorbed into the blood. - More diluted urine is produce. Water potential in blood falls. - When water potential of blood has returned to normal, the osmoreceptors cause the

pituitary to raise its ADH release back to normal level.