SCHOOL OF MEDICINE & HEALTH

SCIENCES

Topic: Homeostasis
Lecture 1
 HOMEOSTASIS
Learning outcomes
 discuss the importance of homeostasis in mammals and explain
the principles of homeostasis.
 define the term negative feedback and explain how it is
involved in homeostatic mechanisms.
 outline the roles of the nervous system and endocrine system
in coordinating homeostatic mechanisms, including
thermoregulation, osmoregulation and the control of blood
glucose concentration.
Cont.
 describe the deamination of amino acids and outline the
formation of urea in the urea cycle (biochemical details of
the urea cycle are not required)
 describe the gross structure of the kidney and the detailed
structure of the nephron with its associated blood vessels
using photomicrographs and electron micrographs.
 describe how the processes of ultrafiltration and selective
reabsorption are involved with the formation of urine in the
nephron.
Cont.
 describe the roles of the hypothalamus, posterior pituitary gland, ADH
and collecting ducts in osmoregulation
 explainhow the blood glucose concentration is regulated by negative
feedback control mechanisms, with reference to insulin and glucagon
 outline the role of cyclic AMP as a second messenger with reference
to the stimulation of liver cells by adrenaline and glucagon
 describe the three main stages of cell signalling in the control of blood
glucose by adrenaline.
 Homeostasis in mammals
 This refers to the maintenance of the constant internal environment
in an organism.
 Substances controlled in homeostasis include:
i. Core body temperature
ii. Blood glucose concentration
iii. Blood pH
iv. Blood water potential
v. Metabolic wastes ( urea and carbon dioxide)
 Principles of Homeostasis
 Principles of homeostasis depend on the following components:
 Receptors: these are cells or specific organs in the body that are
capable of detecting a stimulus, such as a change or deviation in the
external and internal environment.
 Control center: This is also referred to as the integrating center. It
includes the brain and spinal cord. It receives sensory information
from the receptors and signals the effectors to carryout a response.
 Effectors: these are tissues or organs that cause the necessary action
to bring the affected condition back to a normal level after the
stimulus has been received by the receptors.
Role of nervous and endocrine systems in coordinating
homeostasis
ENDOCRINE SYSTEM NERVOUS SYSTEM

Communication by chemical messagers transmitted in the Communication by electrochemical action potentials

blood

Hormones ‘broadcast’ all over the body but influence Action potential are targeted on specific cells.
target organs and tissue cells only

Has effects over several minutes, hours or longer Produces effects within milliseconds

Have glands that secrete hormones Causes muscles to contract

 Homeostatic mechanisms
 Parameters (measurable factor) have their own optimum points(set
points). If there is a change away from this optimum point, the
internal environment needs to return back the optimum point.
 The mechanism that reverses the change in internal conditions so
that it returns back to the optimum is called negative feedback.
 The optimum point for the body is monitored by the receptors .when
receptors detect any change away from the optimum, they send the
information to the control center which then decides the appropriate
response that must be carried out by the effectors.
 Positive feedback is the opposite of negative feedback in that any
change away from a set point is increased (amplified). This is a
mechanism that brings about a large, unstable change in the body. It
is usually harmful, but sometimes can be useful.
 In mammals. regulation of body temperature, blood sugar level and
the concentration of water and ions in blood and tissue fluid
(osmoregulation) are all regulated by negative feedback.
Thermoregulation
 This is the control of body temperature. It involves both
coordination systems – nervous and endocrine. All mammals
generate heat and have ways to retain it within their bodies.
 The heat that mammals generate is released during respiration.
 Much of the heat is produced by liver cells that have a huge
requirement for energy.
 The heat they produce is absorbed by the blood flowing through the
liver and distributed around the rest of the body.
 The hypothalamus in the brain is the central control for body
temperature. This region of the brain receives a constant input of
sensory information about the temperature of the blood and about the
temperature of the surroundings.
 The hypothalamus has thermoreceptor cells that continually
monitor the temperature of the blood flowing through it. The
temperature it monitors is the core temperature –which is 37 °C in
humans.
 This temperature fluctuates a little, but is kept within very narrow
limits by the hypothalamus.
 Excretion
 Manyexcretory products are formed in humans, but two are made in
much greater quantities than others. These are carbon dioxide and urea.
 Carbon dioxide is produced as a waste continuously by cells via aerobic
respiration. The carbon dioxide is transported from the respiring cells
to the lungs, in the bloodstream
 Ureais produced in the liver, from excess amino acids and is
transported from the liver to the kidneys, in solution in blood plasma.
The kidneys remove urea from the blood and excrete it, dissolved in
water, as urine.
Deamination of amino acids
 Excess intake of proteins can lead to high levels of amino acids in the
body. These amino acids cannot be stored, hence the body may use them
for energy through the process of deamination.
 Deamination is the process by which the liver cells (hepatocytes) remove
the amino groups from the amino acids to make use of the potential
energy.
 Thishappens together with the removal of an extra hydrogen atom. The
amino group and the hydrogen atom combine to form ammonia.
 Theremaining part of the amino acid forms the keto acid
which may enter the Krebs cycle and be respired or
converted to fats for storage.
 Urea is less soluble and less toxic, it is formed by
combining ammonia and carbon dioxide through several
reactions.
Urea cycle
The kidneys
 This is the main organ for osmoregulation and excretion of
nitrogenous waste products.
 The cross-sectional area of the kidney is covered by a fairly tough
renal capsule, beneath which lies the cortex.
 The central area is made up of the medulla. Where the ureter joins,
there is an area called the pelvis.
 Each kidney receives blood from a renal artery, and returns blood
via a renal vein. A narrow tube, called the ureter, carries urine from
the kidney to the bladder. From the bladder a single tube, the
urethra, carries urine to the outside of the body
Structure of the kidney and nephron
 Structure of the nephron
 Each kidney contains thousands of microscopic tubes called
nephrons. The beginning of each nephron is a cup-shaped structure
called the renal (Bowman’s) capsule. Its made up of a basement
membrane and podocytes that enables micro molecules to pass
through.
 The capsule is connected to the proximal convoluted tubule
(PCT),that consists of numerous microvilli in the epithelial cells
lining the tubule and large number of mitochondria. The microvilli
increase the surface area for diffusion of substances while the
mitochondria provide ATP used during the uptake of substances
during selective reabsorption.
Structure of the nephron
 Loop of Henle consists of the narrow descending limb with water
permeable walls and the wider ascending limb with water
impermeable cells.
 This allows osmotic gain of water to increase concentration of the
glomerular filtrate and enables Na+ and Cl– to be actively transported
out of the filtrate to decrease its concentration.
 The collecting duct also contains highly permeable walls that allow
water to pass through into the surrounding fluid of the medulla.
Structure of the nephron
 Blood enters the nephron through the afferent arteriole that branches
from the renal artery and is delivered to a network of capillaries
called the glomerulus, found in the Bowman’s capsule.
 Blood leaves the glomerulus in the efferent arteriole. This leads to
another network of capillaries that wraps around the nephron before
delivering blood to the renal vein.
 The afferent arteriole has a wide diameter while the efferent has a
narrow diameter,this enables ultrafiltration to take place between the
glomerulus and Bowman’s capsule.
Structure of the nephron
Structural histology of the kidneys
The diagrams below shows the histology(structure of tissues) of the
kidneys.
 Formation of urine in a nephron
Ultrafiltration
 The blood in the glomerulus is at relatively high pressure, because
the efferent arteriole is narrower than the afferent arteriole. This
forces molecules from blood such as amino acids, water, glucose,
inorganic ions (Na+ and K +) and urea to pass through into the
Bowman’s capsule.
 These molecules make up the glomerular filtrate which seeps
through the Bowman’s capsule with the filtration rate of 125cm 3 per
minute.
 Substances that cannot pass through include red and white blood
cells and plasma proteins (albumin, globulins & fibrinogen).
Formation of urine
 The blood in the glomerular capillaries is separated from the lumen
of the Bowman’s capsule by two cell layers and a basement
membrane. The first cell layer is the lining, or endothelium, of the
capillary which has gaps in it, but there are far more gaps than in
other capillaries.
 Next comes the basement membrane, which is made up of a
network of collagen and glycoproteins.
 The second cell layer is formed from epithelial cells, which make up
the inner lining of the Bowman’s capsule. These cells have many
tiny finger-like projections with gaps in between them, and are
called podocytes.
Ultra-filtration
Composition of Blood and glomerular filtrate
Selective reabsorption
 This happens in the PCT. Some substances that are filtered into the
Bowman’s capsule need to be retained by the body. These include
water, all the glucose and same inorganic ions.
 These substances are therefore taken back into the blood stream
through the walls of the PCT, this is called selective reabsorption.
 The cells in the wall of the tubule have many mitochondria, to
provide ATP for active transport.
Selective re-absorption
 Active transport moves the Na+ ions out of the surface of the cell in
the PCT into the blood. This lowers the concentration of Na+ ions in
the tubule. The Na+ ions diffuse through protein transporters in the
cell membrane within the tubule.
 The protein transporter carry glucose with them. This is called co-
transport. The glucose molecules move through the cell and diffuse
in the blood.
 The movement of ions and glucose into blood decreases the water
potential in the blood.
Selective re-absorption

 The filtrate now has no

glucose, less water and less
Na+ ions.
 About 50% of urea is also
reabsorbed in the PCT.
Re-absorption in the Loop of Henle
 The loop of Henle helps in the buildup of Na+ and Cl– ions into the
medulla and back up into the cortex. This allows for a highly
concentrated urine to be produced.
 As the fluid moves down the descending limb of the loop of Henle,
water moves out through osmosis. By the time the fluid reaches the
bottom of the loop, it has a much lower potential than at the top of
the loop.
 As the filtrate flows up the ascending limp of the loop, Na+ and
Cl– ions move out of the fluid into the surrounding tissues of the
medulla first by diffusion and later by active transport.
Re-absorption in the Loop of Henle
Distal convoluted tubule and collecting duct

 The fluid flowing up the ascending limb of the loop of Henle loses
sodium and chloride ions as it goes, so becoming more dilute and
having a higher water potential.
 The cells of the ascending limb of the loop of Henle and the cells
lining the collecting ducts are permeable to urea, which diffuses into
the tissue fluid. As a result, urea is also concentrated in the tissue
fluid in the medulla.
 The fluid continues round through the distal convoluted tubule into
the collecting duct, which runs down into the medulla again.
Re-absorption
 It therefore passes once again through the regions where the solute
concentration of the tissue fluid is very high and the water potential
very low.
 Water therefore can move out of the collecting duct, by osmosis,
until the water potential of urine is the same as the water potential of
the tissue fluid in the medulla, which may be much greater than the
water potential of the blood.
 At this point, water needs to be regulated so that the cells contain a
stable water content.
SCHOOL OF MEDICINE & HEALTH
SCIENCES

Topic: Homeostasis
Lecture 2
 OSMOREGULATION
 This is the regulation of water content of body fluids. It is an
important part of homeostasis and involves the hypothalamus,
posterior pituitary gland and the kidneys.
 The water potential of the blood is constantly monitored by
specialized sensory neurons in the hypothalamus, known
as osmoreceptors.
 When these cells detect a decrease in the water potential of the
blood, below a set point, nerve impulses are sent along the
neurons to the posterior pituitary gland.
Osmoregulation
Osmoregulation
 These impulses stimulate the release of ADH from the posterior
pituitary gland, where it had been stored after being secreted from
the hypothalamus.
 Molecules of ADH enter the blood capillaries and are carried all
over the body.
 The cells of the collecting ducts are the target cells of ADH.
 ADH acts on the cell surface membranes of the collecting duct cells,
making them more permeable to water than usual.
Osmoregulation
 This change in permeability is brought about by increasing the number of
water permeable channels, known as aquaporins, in the cell surface
membrane of collecting duct cells.
 ADH molecules bind to receptor proteins on the cell surface membranes,
which in turn activate enzymes inside the cells.
 The cells contain ready-made vesicles that have many aquaporins
(channel proteins facilitating transport of water & solute molecules across
biological membranes) in their membrane.
 Once the enzymes in each cell are activated by the arrival of ADH,
these vesicles move towards the cell surface membranes and fuse with
them, hence increasing the membranes’ permeability to water.
Osmoregulation
 Now, as the fluid flows down the collecting duct, water
molecules move through the aquaporins, out of the tubule and into
the tissue fluid.
 This is because the water potential of the tissue fluid in
the medulla is very low and the water potential of the fluid in
the collecting duct is very high.
 The fluid in the duct loses water and becomes more concentrated.
Hence, the volume of urine, which flows from the kidneys into the
bladder, will be lesser and the urine will be less concentrated with
water molecules.
Osmoregulation – high water levels
 When there’s an increase in the water potential of the blood the
osmoreceptors are no longer stimulated and the hypothalamus
stops secreting ADH.
 The effect is that the aquaporins are moved out of the cell surface
membrane of the collecting duct cells, back into the cytoplasm as
part of vesicles.
 This make collecting duct cells impermeable to water.
 This fluid flows down the collecting duct without losing any water,
so a large volume of dilute urine collects in the pelvis, and flows
down the ureter into the bladder.
 The control of blood sugar concentration
 In a healthy human, each 100 cm3 of blood contains between 80-
120 mg of glucose.
 The homeostatic control of blood glucose concentration is carried
out by two hormones secreted by endocrine tissues in pancreas.
 The tissue consists of a group of cells, known as the Islets of
Langerhans, which are scattered throughout the pancreas.
 The islets contain two types of cells:
 α cells (secrete glucagon)
 β cells (secrete insulin)
Increase in Blood Glucose Level
 The α and β cells act as the receptors and the central control of
the homeostatic mechanism with the hormones coordinating the
actions of the effectors.
 As the blood containing high glucose concentration flows through
the pancreas, the α and β cells detect this increase.
 The α cells respond by stopping the secretion of glucagon and the
β cells respond by secreting insulin into the blood plasma to the
target cells.
Blood sugar regulation
Cyclic signaling AMP
 There are insulin receptors on many cells, such as those in the liver,
muscle and adipose (fat storage) tissue
 Insulin is a signaling molecule. It’s a protein and cannot pass
directly through the cell surface membranes.
 It binds to a receptor in the cell membrane and affects the cell
indirectly through the mediations of intracellular messengers.
 Insulin stimulates the cells, containing its specific receptors,
to increase the rate at which they should absorb glucose from the
blood and convert it into glycogen and use it for respiration.
cAMP
 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.
 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.
NB: cAMP is a second messenger used for intracellular transduction
(i.e. helps transfer into cells the effects of hormones which cannot pass
through the cell membrane)
Blood sugar regulation
Blood sugar regulation
 Binding of insulin to the receptors on the plasma membrane of these
cells causes adenyl cyclase to convert ATP into cyclic AMP (cAMP)
 cAMP acts as a second messenger and activates certain enzyme
controlled reactions in the cells to stimulate the opening of glucose
channels in the surface membrane.
 This causes more glucose to enter the cell, which is then converted
to glycogen or fats and subsequently used for respiration
Blood sugar regulation
 Insulin also stimulates the activation of the enzyme glucokinase,
which phosphorylates glucose.
 This traps glucose inside the cells because phosphorylated glucose
cannot pass through the transporters in the cell 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 glycogen
granules in the cell.
Decrease in Blood Glucose Level
 Detected by 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.
 Glucagon binds to different receptor molecules in the cell
membranes of the liver cells.
 This binding activates a G-protein, that in turn activates
an enzyme that catalyzes 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.
Blood sugar regulation
 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 catalyzes 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
Blood sugar regulation
Second messenger - adrenaline
 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.
 DIABETES MELLITUS
 Two forms of diabetes mellitus:
 Type 1: insulin dependent
 Type 2: non – insulin dependent


 Type 1 Diabetes Mellitus:

 In this type, the pancreas seems incapable of secreting insulin.
 This is thought to be due to a deficiency in the gene that codes for
the production of insulin, or due to an attack on the β cells by the
body’s own immune system.
Diabetes mellitus
 Normally, there’s no glucose in the urine, but if the glucose
concentration in the blood becomes very high, the kidneys cannot
reabsorb all the glucose, so that some passes out in the urine. Extra
water and salts accompany this glucose.
 The person consequently feels extremely hungry and thirsty.
 Uptake of glucose in a diabetic person is slow, even when there’s a
plenty of glucose in blood.
Diabetes mellitus
 Thus, cells lack glucose and, metabolize fats and
proteins as alternative energy sources.
 This leads to a buildup of substances in blood, called ketones (keto
acids).
 These are produced when the body switches to metabolizing fats and
they decrease the pH of blood (this can cause comma if
accompanied with dehydration).
 Sufferers of type-1 diabetes receive regular injections of insulin.
Type 2 Diabetes Mellitus:
 In this type the pancreas does secrete insulin, and the liver and
muscle cells don’t respond to it properly.
 This type begins relatively late in life and is often associated
with diet and obesity.
 The symptoms of this diabetes mellitus are the same as the first
one.
 People with type-2 rarely need to have insulin injections; they can
use diet and, regular and frequent exercise to keep their blood
glucose concentration within normal limits.
 URINE ANALYSIS
 The presence of glucose and ketones in urine indicates that a person
may have diabetes.
 The presence of protein in the urine indicates that there is something
wrong with the kidneys. Most protein molecules are too large to be
filtered.
 However, a large quantity or the long-term presence of protein in the
urine indicates that there may be a disease affecting the glomeruli or
there is a kidney infection. Protein in the urine is also associated
with high blood pressure, which is a risk factor in heart disease.
 Dipsticks
 Can be used to test urine for a range of different factors including,
pH, glucose, ketones and proteins.
 Dipsticks for detecting glucose contain the enzymes, glucose
oxidase and peroxidase immobilized on to a small pad on one end
of the stick.
 The pad is immersed in urine and if the urine contain glucose,
glucose oxidase catalyzes a chemical reaction in which glucose is
oxidized into a substance called gluconolactone. Hydrogen
peroxide is also produced.
Urine analysis
 Peroxidase catalyzes a reaction between hydrogen peroxide and a colorless
chemical(chromogen) in the pad to form a brown compound.
 The resulting color of the pad is matched against a color chart. The chart shows
the colors that indicate different concentrations of glucose.
 The larger the amount of glucose present, the darker the color.
 The dipsticks don’t indicate the current blood glucose concentration.
 it shows the glucose level in urine from bladder NOT the current blood sugar
level.
Urinalysis
 Biosensor
 Used to measure the glucose level in the blood
 Biosensor is a device which makes use of a biological molecule to
detect and measure a chemical compound. i.e. a pad impregnated
with glucose oxidase.
 A small sample of blood is placed on the pad which is inserted into
the machine.
 Glucose oxidase catalyzes the reaction to produce
gluconolactone and at the same time, a tiny electric current is
generated.
A biosensor  The current is detected by
an electrode, amplified, and read
by the meter which produces a
reading for blood glucose
concentration within seconds.
 The more glucose that is present,
the greater the current and the
greater the reading from the
biosensor
Stomatal aperture
Osmoregulation in plants
 Stomata have daily rhythms of opening and closing and respond to
changes in environmental conditions to allow diffusion of carbon
dioxide and regulate water loss by transpiration.

Stomata opens due to: Stomata closes due to:

• High light intensity • Darkness
• Low concentration of carbon • High levels of carbon dioxide
dioxide • Low humidity
• High temperature
• Water stress
Opening and closing of stomata
 ATP powers proton pumps to actively transport H+ out of cell
 There is a low concentration of H+ and negative charge inside the
cell --> K+ channels open --> K+ diffuse in
 High concentration of K+ inside the cell decreases water potential
 Water moves in via osmosis
 Water entry increases the volume of the guard cell, causing it
to expand --> open
Osmoregultion in plants
Guard cells
 Each stomatal pore is surrounded by 2 guard cells which:
 open when turgid (gain water)
 close when flaccid (lose water)
Abscisic acid and stomatal closure
 Abscisic acid (ABA) is a stress hormone that is secreted in
response to difficult environmental conditions such as very high
temperatures or much reduced water supplies. ABA triggers
the closure of stomata to reduce transpiration and prevent water
loss.
Osmoregulation in plants
 ABA binds to cell surface receptors, it inhibits proton pumps: stop H+ pumped
out
 stimulates movement of Ca2+ through the cell surface membrane and tonoplast
 Ca2+ acts as a 2nd messenger to activate channel proteins to open that allow
negatively charged ions to leave the guard cell. This in turn
 opens channel proteins that allow K+ to leave the cell
 closes channel proteins that allow K+ to enter the cell
 --> net movement: K+ leaves cell
 Loss of ions = higher water potential inside cell = water passes out by osmosis =
guard cells become flaccid --> stomata close