-The Endocrine System:

Signalling by using hormones:

Explain the terms endocrine gland, exocrine gland, hormone and target tissue.

Explain the meaning of the terms first messenger and second messenger, with reference to adrenaline and cyclic AMP (cAMP)

Describe the functions of the adrenal glands

HORMONES: molecules that are secreted by endocrine glands and are released into the blood. They act as chemical messengers, carrying a signal from the endocrine gland to a specific target organ or tissue.

Another communication system in the body Blood circulation to transport its signals. The

blood system transports materials all over the body; therefore any signal released into the blood will be transported throughout the body

Signals released by the endocrine system are molecules called hormones.

Hormones are released directly into the blood from glands called endocrine glands.

These are ductless glands – they consist of groups of cells that produce and release the hormone straight into the blood capillaries running through the gland.

Endocrine or Exocrine

ENDOCRINE GLAND: a gland that secretes hormones directly into the blood. Endocrine glands have no ducts.

EXOCRINE GLAND: a gland that secretes molecules into a duct that carries the molecules to where they are used.

Two types of gland in our bodies.

1. Endocrine glands release or secrete their hormones directly into the blood- Use delivery tubes2. Exocrine glands do not release hormone.- Have a small tube or duct that carries their secretion to another place. - The exocrine cells are called acinar cells- They’re found in clusters around the pancreatic duct which goes to the duodenum (part of the small

intestine)- The acinar cells secrete digestive enzymes into the pancreatic duct- The enzymes digest food in the duodenum- Salivary glands secrete saliva into a duct. The saliva flows along the duct into the mouth.- Lacrimal glands secrete tears- Mammary glands produce milk-

Targeting the Signal

TARGET CELLS : cells that possess a specific receptor on their plasma (cell surface membrane).The shape of the receptor is complementary to the shape of the hormone molecule. Many similar cells together form a tissue.

Cells receiving a hormone signal must possess a specific complementary receptor on their plasma membrane

The hormone binds to this receptor If all the cells in the body possess such a receptor then all the cells can respond to the signal Each hormone is different from all the others. This means that a hormone can travel around the in the blood without affecting cells that do not possess the

correct specific receptor. The cells that possess the specific receptor on their cell surface membranes are called target cells . They are usually grouped together to form the target tissue .

For this reason the endocrine system can be used to send signals all over the body at the same time . But it can also be used to send very specific signals.

The Nature of Hormones:

There are two types of Hormone:

1. Protein and peptide hormones, and derivatives of amino acids (for example adrenaline, insulin and glucagon)

2. Steroid Hormones (for example the sex hormones)

These two types of hormone works in different ways Proteins are not soluble in the phospholipids membrane and do not enter the cell Steroids , however, can pass through the membrane and actually enter the cell to have a direct effect on the

DNA in the nucleus.

Polypeptide/amino acid derivative hormone such as adrenaline:

1) Hormone (first messenger) approaches receptor site- Adenyl cyclase in inactive when receptor site is empty

2) Hormone fuses to receptor site which activates adenyl cyclase inside the membrane

- Hormone cannot pass through membrane

3) Activated adenyl cyclase converts ATP to cyclic AMP which acts as a second messenger (which causes a cellular response)

- Activates other enzymes

Steroid hormone mechanism of action:

- E.g. Testosterone- No 2nd messenger required

1) Hormone approaches receptor site

2) Hormone combines with receptor to form a complex

3) Hormone-receptor complex passes across the membrane into the cell where it switches on the DNA that produce specific enzymes

The Action of Adrenaline

FIRST MESSENGER: is the hormone that transmits a signal around the body, the second messenger is the cAMP, which transmits a signal inside the cell.

ADENYL CYCLASE: is an enzyme associated with the receptor from many hormones, including adrenaline. It is found on the inside of the cell surface membrane.

Adrenaline is an amino acid derivative Unable to enter the target cell It must cause an effect inside the cell without entering the cell itself The adrenaline receptor on the outside of the cell surface membrane has a

shape complementary to the shape of the adrenaline molecule This receptor is associated with an enzyme on the inner surface of the cell surface membrane. The enzyme

is called adenyl cyclase.

Adrenaline in the blood binds to its specific receptor on the cell surface membrane. The adrenaline molecule is called the First Messenger .

When it binds to the receptor it activates the enzyme adenyl cyclase. The adenyl cyclase converts ATP into cycle AMP (cAMP).

The cAMP is a second messenger inside the cell; the cAMP can then cause an effect inside the cell by activating enzyme action.

The Functions of the Adrenal Glands:

The adrenal glands are found lying anterior (just above) the kidneys – one of each side of the body. Each gland can be divided into a medulla region and a cortex region.

The Adrenal Medulla

The medulla is found in the centre of the gland. The cells in the medulla manufacture and release the hormone adrenaline in response to stress such as pain or shock. The effects of adrenaline are widespread and most cells have adrenaline receptors. The effect of adrenaline is to prepare the body for activity. This includes the following effects:

Relax smooth muscle in the bronchioles Increases stroke volume of the heart Increases heart rate :- More oxygen and glucose for respiration- Remove carbon dioxide faster Cause general vasoconstriction - raises blood pressure- Gas exchange for respiration- More blood flow to muscles Stimulate the conversion of glycogen to glucose- Used as a respiratory substrate Dilate the pupils- Increase vision Increase mental awareness Inhibit the action of the gut

- Prioritises energy Cause body hair to erect (piloerection)- Look bigger and thus more intimidating to threat (if it’s another organism)- see fight and flight notes in F215

The Adrenal Cortex

The adrenal cortex uses cholesterol to produce certain steroid hormones. These have a variety of roles in the body.

The mineralocorticoids (aldosterone) help to control the concentrations of sodium and potassium in the blood.

The glucocorticoids (e.g cortisol) help to control the metabolism of carbohydrates and proteins in the liver.

The Regulation of Blood Glucose

Describe, with the aid of diagrams and photographs, the histology of the pancreas, and outline its role as an endocrine and exocrine gland.

Explain how bloody glucose concentration is regulated, with reference to insulin, glucagon and the liver.

The Pancreas

The pancreas is a small organ lying below the stomach. It is an unusual organ in that it has both exocrine and endocrine functions.

Secretion of Enzymes

The majority of cells in the pancreas manufacture and release digestive enzymes , this is the exocrine function of the pancreas.

The cells are found in small groups surrounding tiny tubules into which they secrete digestive enzymes. The tubules join to make up the pancreatic duct which carries the fluid containing the enzymes into the first

part of the small intestine.

The fluid contains the following enzymes:

Amylase – a carbohydrase Trypsinogen – an inactive protease

The fluid also contains sodium hydrogen carbonate, which makes it alkaline. This helps to neutralise the contents of the digestive system that have just left the acid environment of the stomach.

Secretion of Hormones:

PANCREATIC DUCT: a tube that collects all the secretions from the exocrine cells in the pancreas and carries the fluid to the small intestine.

ISLETS OF LANGERHANS: small patches of tissue in the pancreas that have an endocrine function

ALPHA AND BETA CELLS: the cells found in the islets of Langerhans

ALPHA CELLS: secrete the hormone glucagon

BETA CELLS: secrete the hormone insulin

INSULIN: the hormone, released from the pancreas, that causes blood glucose levels to go down

GLUCAGON: the hormone that causes blood glucose levels to rise.

Certain areas of the pancreas called the islets of Langerhans contain different types of cells. There are two types of cell. 1) Alpha cells : manufacture and secrete the hormone glucagon.2) Beta cells: manufacture and secrete the hormone insulin. The islets are well supplied with blood capillaries and these hormones are secreted directly into the blood. T This is the endocrine function of the pancreas.

The Control of Blood Glucose:

HEPATOCYTES: liver cells. They are specialised to perform a range of metabolic functions.

The concentration of blood glucose is carefully regulated. The cells in the islets of Langerhans monitor the concentration of glucose in the blood. The normal blood concentration is 90mg 100cm-1 (90 mg in every 100cm3 of blood). (4 -6moldm -3 ) If the concentration rises or falls away from the acceptable concentration then the alpha and beta cells in

the islets of Langerhans detect the change and respond by releasing a hormone.

If Blood glucose rises too high:

A high blood glucose concentration is detected by the Beta cells In response the Beta cells secrete insulin into the blood The target cells are the liver cells or hepatocytes, muscle cells and some other body cells, including those in

the brain These possess the specific membrane – bound glycoprotein receptors for insulin When the blood passes these cells the insulin binds to these receptors This activates the adenyl cyclase inside each cell which converts ATP to cAMP (cyclic AMP) The cAMP activates a series of enzyme controlled reactions in the cell.

Insulin has several effects on the cell:

1. More glucose channels are placed into the cell surface membrane.

2. More glucose enters the cell3. Glucose in the cell is converted to

glycogen for storage (glycogenesis) 4. More glucose is converted to fats.5. More glucose is used in respiration.

The increased entry of glucose, through the specific channels, reduces the blood glucose concentrations.

If Blood Glucose Drops Too Low:

A low Blood Glucose concentration is detected by the alpha cells

In response the alpha cells secrete the hormone glucagon

Its target cells are the hepatocytes (liver cells) which possess the specific receptors for glucagon.

The effect of glucagon includes:

1. Conversion of glycogen to glucose (glycogenolysis)2. Use of more fatty acids in respiration3. The production of glucose by conversion from amino acids and fats (gluconeogenesis)4. Increase in the rate of cellular respiration and the use of glucose as a respiratory substrate

The overall effect of these changes is to increase the blood glucose concentration.

Glucagon:

A protein made of a single polypeptide chain Secreted by alpha cells When blood glucose concentration falls below a set point, the alpha cells secrete glucagon Glucagon activates phosphorylase (an enzyme in the liver) which catalyses glycogenolysis (breakdown of

glycogen to glucose) Also increases the conversion of amino acids and glycerol into glucose-6-phosphate

Negative feedback loop:

As well as glucagon, at least 4 other hormones can also increase blood glucose concentrations In times of acute stress or excitement, adrenaline is secreted This causes the breakdown of glycogen in the liver, boosting glucose concentrations When glycogen stores become exhausted, cortisol is secreted by the adrenal glands Cortisol promotes liver cells to convert amino acids and glycerol into glucose The system for regulating bloody glucose levels is self regulating: the blood glucose concentration itself

determines the relative amounts of insulin and glucagon secreted so it remains relatively stable The two corrective mechanisms regulated by glucagon and insulin act antagonistically

Glycogen GlucagonType of compound Carbohydrate (polysaccharide) Hormone/polypeptide/proteinRole of compound Storage

To provide glucose when blood glucose conc. Falls (glycogenolysis)

Binds to cell receptor

Causes conversion of glycogen to glucose (glycogenolysis)

Increases blood glucose conc.Site or production Liver (hepatocytes) Pancreas

Islets of Langerhans (alpha cells)

The Regulation of Insulin Levels

Outline how insulin secretion is controlled, with reference to potassium ion channels and calcium ion channels in β-cells in the islets of Langerhans.

Compare and contrast the causes of type I and type II diabetes mellitus.

Discuss the use of insulin produced by genetically modified bacteria, and the potential use of stem cells, to treat diabetes mellitus.

The Importance of Regulating Insulin Levels

Insulin brings about effects that reduce the blood glucose concentrations. If the blood glucose concentration is too high then it is important that insulin is released from the beta

cells. However, if the blood glucose concentration drops too low it is important that insulin secretion stops .

The Control of Insulin Secretion by beta cells

1) The cell membranes of the Beta cells contain both calcium ion channels and potassium ions channels2) The potassium ion channels are normally open and the calcium ion channels are normally closed.

Potassium ions diffuse out of the cell making the inside of the cell more negative; at rest the potential difference across the membrane is -70mV.

3) When glucose concentrations outside the cell are high, glucose molecules diffuse into the β cell by facilitated diffusion

4) The glucose is quickly used in metabolism (increases rate of respiration) produce ATP.5) The extra ATP causes the potassium channels to close.6) The potassium can no longer diffuse out and this alters the potential difference across the cell membrane –

it become less negative inside.7) The β-cells are depolarised8) This change in potential difference opens the calcium ion channels (voltage gated)9) Calcium ions enter the cell and cause the secretion of insulin by making vesicles containing insulin move to

the cell surface membrane and fuse with it, releasing insulin by exocytosis .

Diabetes Mellitus

DIABETES MELLITUS: a disease in which blood glucose concentrations cannot be controlled effectively.

HYPERGLYCAEMIA: the state in which the blood glucose concentration is too high

Blood glucose levels never remain absolutely constant. After a meal the concentration of glucose will rise and during exercise the concentration of glucose will fall. However, using a negative feedback mechanism the body is able to keep the blood concentration fairly well

controlled within certain limits. Diabetes Mellitus is a disease in which the body can’t control its blood glucose concentration. This can lead to very high concentrations ( hyperglycaemia) of glucose after a meal rich in sugars and other

carbohydrates It can also lead to the concentration dropping too low ( hypoglycaemia ) after exercise or after fasting.

Type 1 Diabetes:

Type 1 diabetes is also known as insulin dependent diabetes. It is often called juvenile – onset diabetes because it usually starts in childhood It is thought to be the result of an autoimmune response in which the body’s own immune system attacks

the beta cells and destroys them It may also result from a viral attack The body is no longer able to manufacture sufficient insulin and cannot store excess glucose as glycogen.

Type 2 Diabetes:

Type 2 Diabetes is also known as non-insulin-dependent diabetes A person with type 2 diabetes can still produce insulin. However, as people age, their responsiveness to insulin declines This is probably because the specific receptors on the surface of the liver and muscle cells decline and the

cells lose their ability to respond to the insulin in the blood The levels of insulin secreted by the Beta cells may also decline

It is thought that anyone who lives long enough will eventually become diabetic.

Certain factors seem to bring on earlier onset of type 2 diabetes. These include:

Obesity A diet high in sugars, particularly refined sugars Being of Asian or Afro – Caribbean origin Family History. Lack of physical activity High blood pressure Excessive alcohol intake

Treatment of Diabetes:

Type 2 diabetes - Treated with careful monitoring and control of the diet- Care is taken to match carbohydrate intake and use- This may be eventually be supplemented by insulin injections or use of other drugs which slow down the

absorption of glucose from the digestive system.- Weight loss may help Type 1 diabetes - Treated using insulin injections. - The blood glucose concentration must be monitored and the correct dose of insulin must be administered

to ensure that the glucose concentration remains fairly stable.

The Source of Insulin:

Insulin used to be extracted from the pancreas of animals – usually from pigs as this matches the human insulin most closely.

However, more recently insulin can be produced from bacteria that have been engineered to manufacture human insulin.

The advantage of using insulin from genetically engineered bacteria includes:

It is an exact copy of human insulin; therefore it is faster acting and more effective. There is less chance of developing tolerance to the insulin. There is less chance of rejection to an immune response or an allergic response There is a lower risk of infection. It is cheaper to manufacture the insulin than to extract it from animals. The manufacturing process is more adaptable to demand. Some people are less likely to have moral objections to using the insulin produced from bacteria than to

using that extracted from animals.

A New Way to Treat Diabetes:

STEM CELLS: are unspecialised cells that have the potential to develop into any type of cell

GENETICALLY ENGINEERED: bacteria are those in which the DNA has been altered, in this case a gene coding for human insulin has been inserted into the DNA of the bacteria

Recent research has shown that it may be possible to treat type 1 diabetes using stem cells. Stem cells are not yet differentiated and can be induced to develop into a variety of cell types The most common source of stem cells are bone marrow and the placenta However, Scientists have recently found precursor cells in the pancreas of adult mice

These cells are capable of developing into a number of cell types and may be true stem cells If similar cells can be found in the human pancreas then they could be used to produce new beta cells in

patients with type 1 diabetes

Control of Heart Rate in Humans

Outline the hormonal and nervous mechanism involved in the control of heart rate in humans.

The Human Heart

CELL METABOLISM: the result of all the chemical reactions taking place in all the cytoplasm

The human heart pumps blood around the circulatory system. Blood supplies the tissues with oxygen and nutrients such as glucose, fatty acids and amino acids. It also removes waste products, such as carbon dioxide and urea, from the tissues so that they do not

accumulate and inhibit cell metabolism. The requirements of the cells vary according to their level of activity When you are being physically active your muscle cells need more oxygen and glucose and your heart

muscle cells need more oxygen and fatty acids. These cells also need to remove more Carbon Dioxide.

It is therefore, important that the heart can adapt to meet the requirements of the body.

Structure of the nervous system:

Split into two systems1. CNS: brain and spinal cord2. PNS (peripheral nervous system): Somatic nervous system: controls conscious activities Autonomic nervous system: controls unconscious activities (e.g. heart rate)- Sympathetic nervous system- ‘fight or fight’, Releases neurotransmitter called noradrenaline- Parasympathetic nervous system – ‘rest and digest’. Releases neurotransmitter acetylcholine

How the Heart Adapts to Supply More Oxygen and Glucose:

The most obvious change in the activity of the heart is an increase in the number of beats per minute, This is known as the heart rate.

The heart can increase the strength of it contractions. It can also increase the volume of blood pumped per beat (stroke volume)

Control of Heart Rate:

MYOGENIC: muscle tissue can initiate its own contractions.

PACEMAKER: is a region of tissue in the right atrium wall that can generate an impulse and initiates the contraction of the chambers.

MEDULLA OBLONGATA: is found at the base of the brain. It is the region of the brain that coordinates the unconscious functions of the body such as breathing rate and heart rate.

THE ACCELERATOR NERVE: and the vagus nerve run from the medulla oblongata to the heart.

CARDIOVASCULAR NERVE: is a specific region of the medulla oblongata that receives sensory inputs about the levels of physical activity, blood carbon dioxide concentration and blood pressure. It sends nerve impulses to the SAN in the heart to alter the frequency of excitation waves.

The rate at which the heart beats is affected by a number of factors:

The heart muscle is myogenic The heart contains its own pacemaker – this is called the sinoatrial node (SAN).- The SAN is a region of tissue that can initiate an action potential, which travels as a wave of excitation over

the atria wall, through the AVN (atrioventricular node) and down the Purkyne fibres to the ventricles, causing them to contract.

- The rate at which the SAN generates electrical impulses (i.e. heart rate) is unconsciously controlled by the cardiovascular centre in the medulla oblongata

The heart is supplied by nerves from the Medulla Oblongata of the brain. - These nerves connect to the SAN- These do not initiate a contraction, but they can affect the frequency of the contractions. - Action potentials sent down the accelerator nerve increase the heart rate.- Action potentials sent down the vagus nerve reduce the heart rate. The heart muscle responds to the presence of the hormone adrenaline in the blood.

Detecting the change:

Need to alter heart rate to respond to internal stimuli e.g. to prevent fainting due to low blood pressure Internal stimuli are detected by pressure and chemical receptors- Baroreceptors : . Pressure receptors found in the aorta, the vena cava and carotid arteries. They’re

stimulated by high and low blood pressure- Chemoreceptors : chemical receptors in the aorta, the carotid arteries and in the medulla oblongata. They

monitor the oxygen level in the blood and also carbon dioxide and pH (which are indicators of oxygen level) Electrical impulses from the receptors are sent to the cardiovascular centre along sensory neurones The CV centre processes the information and sends impulse to the SAN along motor neurones

Interaction between control mechanisms:

The various factors that affect heart rate must interact in a coordinated way to ensure that the heart beats at the most appropriate rate.

Under resting conditions the heart rate is controlled by the SAN- This has a set frequency varying from person to person, at which it initiates waves of excitation

CO2+H 2O→H2CO3 (carbonic acid)

H 2C O3→H+¿+H 2CO3−¿ ¿¿

- The frequency of waves is typically 60-80 per minute- However, the frequency of these excitation waves can be controlled by the cardiovascular centre in the

medulla oblongata.

There are many factors that affect the heart rate:

1. Movement of the limbs is detected by stretch receptors in the muscles- These send impulses to the cardiovascular centre informing it that extra oxygen may soon be needed. This

tends to increase heart rate.2. Adrenaline is secreted in response to stress, shock, anticipation or excitement- The presence of adrenaline in the blood increases the heart rate- Causes cardiac muscle to contract more frequently and with more force, so heart rate increases and pumps

more blood- This helps to prepare the body for activity.

Control of heart rate in response to different stimuli

High blood pressure:

- Blood pressure is monitored by stretch receptors in the walls of the carotid sinus- This is a small swelling in the carotid artery- If blood pressure rises too high, perhaps during vigorous exercise, the stretch receptors send signals to the

cardiovascular centre- This then sends impulses along the parasympathetic neurones- These release acetylcholine, which binds to receptors on the SAN- This responds by reducing the heart rate in order to decrease blood pressure back to normal

Low blood pressure:

- Barorecptors detect low blood pressure- send impulses to the cardiovascular centre- This then sends impulses along the sympathetic neurones- These release noradrenaline, which binds to receptors on the SAN- This responds by increasing the heart rate in order to increase blood pressure back to normal

Low blood oxygen, high CO2 or low blood pH:

- When we exercise the muscles produce more carbon dioxide- Some of this reacts with the water in the blood plasma and

reduces pH by producing carbonic acid which reduces pH- The change in pH is detected by chemoreceptors in the carotid arteries, the aorta and the brain. - The chemoreceptors send impulses along parasympathetic neurones- These secrete acetylcholine, which binds to receptors on the SAN- This causes the heart rate to decrease in order to return oxygen, CO2 and pH levels back to normal

High blood oxygen, low CO2 or high blood pH:

- When we stop exercising the concentration of carbon dioxide in the blood falls

- This reduces the activity of the accelerator pathways. - Therefore the heart rate declines.- The change in pH is detected by chemoreceptors - The chemoreceptors send impulses along sympathetic neurones- These secrete noradrenaline, which binds to receptors on the SAN- This causes the heart rate to increase in order to return oxygen, CO2 and pH levels back to normal

ADENYL CYCLASE: is an enzyme associated with the receptor from many hormones, including adrenaline. It is found on the inside of the cell surface membrane.

ALPHA AND BETA CELLS: the cells found in the islets of Langerhans

ALPHA CELLS: secrete the hormone glucagon

BETA CELLS: secrete the hormone insulin

CARDIOVASCULAR NERVE: is a specific region of the medulla oblongata that receives sensory inputs about the levels of physical activity, blood carbon dioxide concentration and blood pressure. It sends nerve impulses to the SAN in the heart to alter the frequency of excitation waves.

DIABETES MELLITUS: a disease in which blood glucose concentrations cannot be controlled effectively.

ENDOCRINE GLAND: a gland that secretes hormones directly into the blood. Endocrine glands have no ducts.

EXOCRINE GLAND: a gland that secretes molecules into a duct that carries the molecules to where they are used.

FIRST MESSENGER: is the hormone that transmits a signal around the body, the second messenger is the cAMP, which transmits a signal inside the cell.

GENETICALLY ENGINEERED: bacteria are those in which the DNA has been altered, in this case a gene coding for human insulin has been inserted into the DNA of the bacteria

GLUCAGON: the hormone that causes blood glucose levels to rise.

HEPATOCYTES: liver cells. They are specialised to perform a range of metabolic functions.

HORMONES: molecules that are secreted by endocrine glands and are released into the blood. They act as chemical messengers, carrying a signal from the endocrine gland to a specific target organ or tissue.

HYPERGLYCAEMIA: the state in which the blood glucose concentration is too high

INSULIN: the hormone, released from the pancreas, that causes blood glucose levels to go down

ISLETS OF LANGERHANS: small patches of tissue in the pancreas that have an endocrine function

MEDULLA OBLONGATA: is found at the base of the brain. It is the region of the brain that coordinates the unconscious functions of the body such as breathing rate and heart rate.

MYOGENIC: muscle tissue that can initiate its own contractions.

PACEMAKER: is a region of tissue in the right atrium wall that can generate an impulse and initiates the contraction of the chambers.

PANCREATIC DUCT: a tube that collects all the secretions from the exocrine cells in the pancreas and carries the fluid to the small intestine.

STEM CELLS: are unspecialised cells that have the potential to develop into any type of cell

TARGET CELLS : cells that possess a specific receptor on their plasma (cell surface membrane).The shape of the receptor is complementary to the shape of the hormone molecule. Many similar cells together form a tissue.

THE ACCELERATOR NERVE: and the vagus nerve run from the medulla oblongata to the heart.