A Level Biology

Homeostasis is the maintenance

of a stable internal environment

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 1.
Principles of homeostasis and negative
feedback

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To function efficiently, organisms have control systems to keep internal conditions near
constant, a feature known as homeostasis.
This requires information about conditions inside the body and the surroundings, which
are detected by sensory cells.

Some of the physiological factors controlled in homeostasis in mammals are:

 Core body temperature
 Metabolic wastes, particularly carbon dioxide and urea
 Blood pH
 Blood glucose concentration
 Water potential of the blood
 The concentrations in the blood of the respiratory gases, oxygen and
carbon dioxide

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Internal environment

▪ The internal environment of an organism refers to all the conditions inside the body.
These are the conditions in which the cells function. For a cell, its immediate
environment is the tissue fluid that surrounds it.
▪ Many features of the tissue fluid influence how well the cell functions.
▪ Three features of tissue fluid that influence cell activities are:
1. Temperature: low temperatures slow down metabolic reactions; at high temperatures
proteins, including enzymes, are denatured and cannot function.

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2. Water potential - if the water potential decreases, water may move out of cells by
osmosis, causing metabolic reactions in the cell to slow or stop; if the water potential
increases, water may enter the cell causing it to swell and maybe burst.
3. Concentration of glucose - glucose is the fuel for respiration, so lack of it causes
respiration to slow or stop, depriving the cell of an energy source; too much glucose
may cause water to move out of the cell by osmosis, again disturbing the metabolism
of the cell.

▪ In general, homeostatic mechanisms work by controlling the composition of blood,

which therefore controls the composition of tissue fluid.
▪ There are control mechanisms for the different aspects of the blood and tissue fluid.
These include the three psychological factors listed above.

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Homeostatic control
▪ Most control mechanisms in living organisms use a negative feedback control loop to
maintain homeostatic balance.
▪ This involves a receptor (or sensor) and an effector. Effectors include muscles and
glands.
▪ The receptor detects stimuli that are involved with the condition (or physiological
factor) being regulated.
▪ A stimulus is any change in a factor, such as a change in blood temperature or the
water content of the blood.
▪ The body has receptors which detect external stimuli and other receptors that detect
internal stimuli. These receptors send information about the changes they detect
through the nervous system to a central control in the brain or spinal cord.
▪ This sensory information is known as the input.
▪ The central control instructs an effector to carry out an action, which is called the
output.
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▪ These actions are sometimes called corrective actions as their effector is to correct
(or reverse) the change.
▪ Continuous monitoring of the factor by receptors produces a steady stream of
information to the control centre that makes continuous adjustments to the output.
▪ As a result, the factor fluctuates around a particular ‘ideal’ value, or set point.
▪ This mechanism to keep changes in the factor within narrow limits is known as
negative feedback.
▪ In these systems, an increase in the factor results in something happening that
makes the factor decrease.
▪ Similarly if there’s a decrease in the factor, then something happens to make it
increase.
▪ Homeostatic mechanisms involve negative feedback as it minimises the difference
between the actual value of the factor and the ideal value or set point.
▪ The factor never stays exactly constant, but fluctuates a little above and a little below
the set point.
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▪ The homeostatic mechanisms in mammals
require information to be transferred between
different parts of the body. There are two
coordination systems in mammals that do this:
the nervous and the endocrine system.
1. In the nervous system, information in the form
of electrical impulses is transmitted along
nerve cells (neurones).
2. The endocrine system uses chemical
messengers called hormones that travel in
the blood, in a form of long- distance cell
signalling.

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 2.
Control of blood glucose concentration

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▪ Carbohydrate is transported through
the human bloodstream in the form
of glucose in solution in the blood
plasma. Glucose is converted into
the polysaccharide glycogen, a
large, insoluble molecule made up
of many glucose units linked
together by 1-4 glycosidic bonds
with 1-6 branching points.
▪ Glycogen is a short term energy
store that is found in liver and
muscle cells and is easily converted
to glucose.
2D cross sectional
view of glycogen

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▪ In a healthy human, each 100cm3 of blood normally contains between 80 and 120
mg of glucose.
▪ If the concentration decreases below this, cells may not have enough glucose for
respiration, and may be unable to carry out their normal activities. This is especially
important for cells that can respire only glucose, such as brain cells.
▪ Very high concentrations of glucose in the blood can als cause major problems, again
upsetting the normal behaviour of cells.
▪ The homeostatic control of blood glucose concentration is carried out by two
hormones secreted by endocrine tissue in the pancreas. This tissue consists of
groups of cells, known as the islets of Langerhans, which are scattered throughout
the pancreas.
▪ The word islet means a small island, as you might find in a river. The islets contain
two types of cells:
1. α cells secrete glucagon
2. Β cells secrete insulin

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▪ The α and β cells act as the receptors and the central control for this homeostatic
mechanism; the hormones glucagon and insulin coordinate the actions of the
effectors.
▪ After a meal containing carbohydrate, glucose from the digested food is absorbed
from the small intestine and passes into the blood. As this blood flows through the
pancreas, the α and β cells detect the increase in glucose concentration.
▪ The α cells respond by stopping the secretion og glucagon, whereas the β cells
respond by secreting insulin into the blood plasma.
▪ The insulin is carried to all parts of the body, in the blood.
▪ Insulin is a signalling molecule. As it is a protein, it cannot pass through cell
membranes to stimulate the mechanisms within the cell directly.
▪ Instead, insulin binds to a receptor in the cell surface membrane and affects the cell
indirectly through the mediation of intracellular messengers.

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▪ There are insulin receptors on many cells, such as those in the liver, muscle and
adipose (fat storage) tissue.
▪ Insulin stimulates cells with these receptors to increase the rate at which they absorb
glucose from the blood, convert it into glycogen and use it in respiration. This results
in a decrease in the concentration of glucose in the blood.
▪ Glucose can only enter cells through transporter proteins known as GLUT.
▪ There are several different types of GLUT proteins. Muscle cells have the type called
GLUT4. Normally, the GLUT proteins are kept in the cytoplasm in the same way as
the aquaporins in collecting duct cells.
▪ When insulin molecules bind to receptors on muscle cells, the vesicles with GLUT4
proteins are moved to the cell surface membrane and fuse with it.
▪ GLUT4 proteins facilitate the movement of glucose into the cell.
▪ Brain cells have GLUT1 proteins and liver cells have GLUT2 proteins, which are
always in the cell surface membrane, and their distribution is not altered by insulin.

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▪ Insulin also stimulates the activation of the enzyme glucokinase, which
phosphorylates glucose. This traps glucose inside cells, because phosphorylated
glucose cannot pass through the transporters in the cell surface membrane.
▪ Insulin also stimulates the activation of two other enzymes, phosphofructokinase and
glycogen synthase, which together add glucose molecules to glycogen.
▪ This increases the size of the glycogen granules inside the cell.
▪ A decrease in blood glucose concentration is detected by the α and β cells in the
pancreas.
▪ The α cells respond by secreting glucagon, while the β cells respond by stopping the
secretion of insulin.
▪ The decrease in the concentration of insulin in the blood reduces the rates of uptake
and use of glucose by liver and muscle cells. Uptake still continues, but at a lower
rate.
▪ Glucagon binds to different receptor molecules in the cell surface membranes of liver
cells.

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▪ The binding of glucagon to a receptor activates a G protein that in turn activates an
enzyme within the membrane that catalyses the conversion of ATP to cyclic AMP,
which is a second messenger.
▪ Cyclic AMP binds to kinase enzymes within the cytoplasm that activate other
enzymes. Kinase enzymes activate enzymes by adding phosphate groups to them in
a process known as phosphorylation. This enzyme cascade amplifies the original
signal from glucagon.
▪ Glycogen phosphorylase is at the end of the enzyme cascade: when activated, it
catalyses the breakdown of glycogen to glucose. It does this by removing glucose
units from the numerous ‘ends’ of glycogen.
▪ This increases the concentration of glucose inside the cell so that it diffuses out
through GLUT2 transporter proteins into the blood.
▪ Glucose is also made from amino acids and lipids in a process known as
gluconeogenesis, which literally means the formation of ‘new’ glucose.

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▪ As a result of glucagon secretion, the liver releases extra glucose to increase the
concentration in the blood. Muscle cells do not have receptors for glucagon and so
do not respond to it.
▪ Glucagon and insulin work together as part of the negative feedback system in which
any deviation of the blood glucose concentration from the set point stimulates actions
by effectors to bring it back to normal.
▪ Blood glucose concentrations never remain constant, even in the healthiest person.
One reason for this is the inevitable time delay between a change in the blood
glucose concentration and the onset of actions to correct it.
▪ Time delays in control systems result in oscillation, where things do not stay
absolutely constant but sometimes rise slightly above and sometimes drop slightly
below the ‘required’ level.

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▪ The hormone adrenaline also increases the concentration of blood glucose.
▪ It does this by binding to different receptors on the surface of liver cells that activate
the same enzyme cascade and lead to the same end result - the breakdown of
glycogen by glycogen phosphorylase.
▪ Adrenaline also stimulates the breakdown of glycogen stores in muscle during
exercise.
▪ The glucose produced remains in the muscle cells where it is needed for respiration.

Formation of glycogen from glucose ----------> glycogenesis

Breaking down of glycogen -----------> glycogenolysis

Formation of glucose from non-carbohydrates ----------> gluconeogenesis

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Diabetes mellitus

▪ Sugar diabetes, or diabetes mellitus, is one of the most common metabolic diseases
in humans.
▪ In 2013, the International Diabetes Federation estimated that 382 million people, or
approximately 8,3% of the world’s adult population, had this disease.
▪ Although the percentages are higher among some ethnic groups and in some
countries than others, it is a disease that is increasing steeply everywhere.

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Type 1 and Type 2 diabetes

▪ There are two forms of sugar diabetes. In insulin- dependent diabetes, which is
also known as type 1 diabetes, the pancreas seems to be incapable of secreting
sufficient insulin. It is thought that this might be due to a deficiency in the gene that
codes for the production of insulin, or because of an attack on the β cells by the
person’s own immune system. Type 1 diabetes is sometimes called juvenile- onset
diabetes, because it usually begins very early in life.
▪ The second form of diabetes is called non-insulin-dependent diabetes or type 2
diabetes. In this form of diabetes, the pancreas does secrete insulin, but the liver
and the muscle cells do not respond properly to it. Type 2 diabetes begins relatively
late in life and is often associated with diet and obesity.

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▪ The symptoms of both types of diabetes mellitus are the same.
▪ After a carbohydrate meal, glucose is absorbed into the blood, and the concentration
increases and stays high.
▪ Normally there is no glucose in urine, but if the glucose concentration in the blood
becomes very high, the kidney cannot reabsorb all the glucose, so that some passes
out in the urine.
▪ Extra water and salts accompany this glucose, and the person consequently feels
extremely hungry and thirsty.
▪ In a diabetic person, uptake of glucose into cells is slow; even when there is plenty of
glucose in the blood. Thus cells lack glucose and metabolise fats and proteins as
alternative energy sources.
▪ This can lead to a build-up of substances in the blood called keto-acids (or ketones).
These are produced when the body switches to metabolising fat and they decrease
the blood pH.
▪ The combination of dehydration. Salt loss and low blood pH can cause coma in
extreme situations.

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▪ Between meals, the blood glucose concentration of a person with untreated diabetes
may decrease steeply.
▪ This is because there is no glycogen to mobilise, as it was not stored when there was
plenty of glucose.
▪ Once again, coma may result , this time because of a lack of glucose for respiration.
▪ People with type 1 diabetes receive regular injections of insulin, which they learn to
do themselves.
▪ They must also take blood samples to check that the insulin is effective.
▪ Some people have mini-pumps which deliver the exact volumes of insulin that they
need when they need them. A carefully controlled diet also helps to maintain a near-
constant concentration of glucose in the blood.
▪ People with type 2 diabetes rarely need to have insulin injections; instead they can
use diet and regular and frequent exercise to keep their blood glucose within normal
limits.
▪ Diabetics now receive insulin made by genetically engineered cells.

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A growing health problem - Type 2 diabetes

▪ Type 2 diabetes is emerging as a very common health issue in the UK. This is linked
to the growing problem of obesity caused by the consumption of unhealthy food and
lack of physical exercise.
▪ Additional health problems such as kidney failure and visual impairment could also
occur because of type 2 diabetes. Therefore health advisors are keen to spread
awareness among the general public regarding the risks of type 2 diabetes and tips
to prevent it from happening.
▪ Some people believe that the food industry has a part to play in managing this issue.

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In order to eliminate the risk of getting
type 2 diabetes, health advisors have
recommended to follow the guidelines
below.

1. Consume a diet rich in fruits,

vegetables and whole grains, while
reducing the intake of salt, sugar
and fat.
2. Exercise regularly.
3. Reduce weight if required.

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The goal of certain campaigns like
‘Change4Life’ is to educate people about
having a healthy diet and lifestyle in order
to decrease the risk of developing diseases
like type 2 diabetes.

The food industry has been challenged by

the health advisors to:
a) minimise advertisements about junk
food.
b) improve the nutritional value of products.
c) use clear labelling on products to
facilitate the consumers in making healthy
choices when buying.

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 3.
Control of blood water potential

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Gross structure of kidneys
▪ Kidneys are bean shaped and reddish brown in colour.
▪ The medial border is concave and the lateral border is convex.
▪ There is a hilus in the medial border of each kidney.
▪ Each kidney is covered by a capsule which is a white fibrous tissue.
▪ The wall of a kidney divides into two as external renal cortex and the internal renal
medulla.
▪ Medulla is made out of cone shaped renal pyramids.
▪ Each kidney may consist of 8-18 renal pyramids.

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Microscopic structure of a kidney
▪ The kidney is made out of uriniferous tubules.
▪ They divide into two parts.
1. Nephron
2. Collecting duct
▪ Nephron is the main functional and the structural unit of the kidney.
▪ Each kidney has around one million nephrons.
▪ Small amount of connective tissues, blood vessels, nerves and lymph vessels are
also present within the uriniferous tubules.

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Structure of a nephron
▪ It is a microscopic structure.
▪ Each nephron has a tubular structure. The free end is closed and the other end
opens into a collecting duct.
▪ The nephron consists of following structures.
1. Bowman’s capsule (glomerular capsule)
2. Proximal convoluted tubule
3. Descending limb of loop of Henle
4. Proper loop of Henle
5. Ascending limb of loop of Henle
6. Distal convoluted tubule

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Formation of urine
This takes place in three major steps.

1. Glomerular ultrafiltration
2. Tubular selective reabsorption
3. Tubular secretion

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Glomerular ultrafiltration
▪ Filtering substances present in blood according to certain molecular weights under
high pressure, through the pores of capillaries of glomerular wall and the inner wall of
Bowman’s capsule to form glomerular filtrate is known as ultrafiltration.
▪ This depends on two major factors.
1. Size of the pores present in glomerular capillaries and in between podocytes
(0.1µm).
2. Blood pressure built within the glomerulus.
▪ Due to the difference in diameter, pressure within the glomerulus is very high.
▪ Blood osmotic pressure = 30 Hgmm
▪ Blood hydrostatic pressure = 70 Hgmm
▪ Ability of filtering = 40 Hgmm
▪ Hydrostatic pressure acts against the above = 5 Hgmm. Therefore the net filtering
ability = 40-5 = 35 Hgmm.

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 The blood plasma entering the capsule
due to the above pressure difference is
known as the glomerular filtrate.
 This contains all the substances present
in blood except blood cells and blood
proteins.
 Composition of the glomerular filtrate:
 Water, glucose, amino acid, ions,
peptones, urea, uric acid, some drugs,
vitamins, creatinine.
 The basement layer is the only obstacle
which prevents the entering of blood cells
and the proteins to the glomerular filtrate.

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Tubular selective reabsorption
A. At proximal convoluted tubule (PCT)
▪ 80% of the water is reabsorbed according to a water potential gradient without
spending energy (passively).
▪ The above mentioned water is reabsorbed irrespective of the amount of water
present in the body. Hence it is known as obligatory renal absorption.
▪ All the other substances get reabsorbed by PCT against the concentration gradient.
Hence it requires energy (active reabsorption).
▪ Following changes take place under active reabsorption.
a) All the glucose present in the filtrate is reabsorbed actively by PCT. The ability
of reabsorbing substances by the PCT is known as the renal threshold value.
Each substance has a significant renal threshold value. For glucose, it’s 180
mg/100 ml which is a high value.

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If the blood glucose value exceeds this, the excess amount will not be reabsorbed by
PCT.
The excess amount will be passed out through urine and this condition is called diabetes
mellitus.
b) Sodium ions (50%) and amino acids are actively reabsorbed by PCT.
c) Vitamin C is also reabsorbed actively by PCT.
d) Chloride ions and 50% of the urea is reabsorbed passively.
e) Creatinine and sulphate ions are not reabsorbed at PCT.

B. At the loop of Henle

▪ When blood flows along the vasa recta capillaries, it recieves sodium ions actively and
chloride ions passively.
▪ This increases the ion concentration of the blood.
▪ Then the blood flows parallel and opposite direction towards the filtrate which flows
downwards along the descending limb.

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▪ When these two streams come into contact closely, sodium ions and chloride ions
enter the filtrate passively increasing its concentration.
▪ Due to this, the filtrate becomes hypertonic when it reaches the proper loop of Henle.
▪ Some amount of water is also reabsorbed into the blood passively at the descending
limb of loop of Henle.
▪ When hypertonic glomerular filtrate flows along the ascending limb towards DCT, it
becomes hypotonic due to:
a) Reabsorption of sodium ions actively and chloride ions passively into the blood.
b) Not reabsorbing water into the blood because the wall of the ascending limb is
impermeable to water.

C. At distal convoluted tubule (DCT)

▪ Sodium ions are reabsorbed actively according to the amount present in the blood.

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▪ This is controlled by aldosterone hormone.
▪ DCT has an ability to reabsorb 15% of water according to the osmotic pressure in
blood. This is controlled by the ADH hormone.
▪ Chloride ions and bicarbonate ions are reabsorbed passively according to the blood
pH value.
▪ The cells of DCT secrete hydrogen ions and ammonium ions into the filtrate actively.

D. At the collecting duct

▪ When the glomerular filtrate flows along this, it meets the osmotic pressure gradient
which exists from cortex to the medulla.
▪ About 4.5% of water can be reabsorbed when hormone ADH is present.
▪ At the end, hypertonic urine is formed.

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Tubular secretion
▪ When glomerular filtrate flows along the tubule, following substances are secreted
into it by the cells of tubule.
a) Hydrogen ions, ammonium ions and creatinine are secreted by PCT.
b) DCT secretes hydrogen ions, potassium ions, ammonium ions and some drugs.
▪ Two streams of fluids which flow in opposite directions while associating very closely
is known as a counter current system.
▪ This system is seen in the kidney in between the vasa recta and the ascending,
descending and the proper loop of Henle.
▪ The function of this system is to maintain an osmotic pressure gradient from the
cortex to medulla.

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Osmoregulation
▪ Osmoregulation is the control
of the water potential of body
fluids.
▪ This regulation is an important
part of homeostasis and
involves the hypothalamus,
posterior pituitary and the
kidneys.

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▪ When blood osmotic pressure is high, osmoreceptors present in the hypothalamus get
stimulated. Then the posterior pituitary is stimulated by an impulse generated from the
hypothalamus.
▪ Then ADH is released by the posterior pituitary which increases the permeability of
DCT and the collecting duct for water. This increases the reabsorption of water.
▪ As a result, the osmotic pressure is reduced and returns to its normal value.
▪ Hypothalamus is stimulated by the reset normal value which then stops the above
process.
▪ When blood osmotic pressure decreases, the release of ADH is reduced. This
decreases the permeability of DCT and the collecting ducts for water. Then more
water is removed.
▪ Urine becomes hypotonic (diluted).
▪ When necessary amount of ADH is not secreted, more amount of water gets removed
by urine.
▪ This causes the dehydration of body resulting in a condition known as diabetes
insipidus.
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