6.

4 Homeostasis
6.4.1 Principles of homeostasis and negative feedback

Homeostasis in mammals

● Maintenance of a stable internal environment within restricted limits

● By physiological control systems (normally involve negative feedback)

Examples: core temperature, blood pH, blood glucose concentration, blood water potential

Importance of maintaining stable core temp and blood pH: enzyme activity

Enzymes have an optimum temperature and pH.

Core temperature Blood pH

Too ● Hydrogen bonds in tertiary structure break
high ● Enzymes denature; active sites change shape
and substrates can’t bind
● So fewer enzyme-substrate complexes
Too ● Not enough kinetic energy
low ● So fewer enzyme-substrate complexes
Above or below optimal pH:
● Ionic / hydrogen bonds in tertiary
structure break
● Enzymes denature; active sites change
shape and substrates can’t bind
● So fewer enzyme substrate complexes

Importance of maintaining stable blood glucose concentration in terms of

availability of respiratory substrate and water potential of blood

Too low (hypoglycaemia) Too high (hyperglycaemia)

● Not enough glucose for respiration ● Water potential of blood decreases

● So less ATP produced ● Water lost from tissue to blood via osmosis
● Active transport etc. can’t happen → cell death ● Kidneys can’t absorb all glucose → more water
lost in urine causing dehydration
Negative vs. positive feedback

Many conditions in the body are controlled by negative feedback systems, eg. control of body temperature

Negative feedback Positive feedback

1. Receptors detect change from optimum 1. Receptors detect change from normal
2. Effectors respond to counteract change 2. Effectors respond to amplify change
3. Returning levels to optimum / normal 3. Producing a greater deviation from normal

→ involved in homeostasis → not involved in homeostasis

Examples: control of blood glucose concentration, Examples: onset of contractions in childbirth, blood
blood pH, core temperature, blood water potential, clotting
blood pressure

Example of negative feedback: control of blood glucose concentration

Students should be able to interpret information relating to examples of negative and positive feedback.

Importance of conditions being controlled by separate mechanisms involving

negative feedback

● Departures in different directions from the original state can all be controlled/reversed
● Giving a greater degree of control (over changes in internal environment)
6.4.2 Control of blood glucose concentration

Factors that influence blood glucose concentration

● Consumption of carbohydrates → glucose absorbed from intestine to blood

● Rate of respiration of glucose - eg. increases during exercise due to muscle contraction

Glycogenesis, glycogenolysis and gluconeogenesis also affect blood glucose concentration controlled by the
action of hormones insulin, glucagon and adrenaline.

Role of the liver in glycogenesis, glycogenolysis and gluconeogenesis

Glycogenesis Converting glucose → glycogen

Glycogenolysis Converting glycogen → glucose

Gluconeogenesis Converting amino acids and/or

glycerol → glucose

⭐Memory tip ⭐ to remember what these words mean,

break them down → lysis = splitting, neo = new,
genesis = creation

The action of insulin (to decrease blood glucose conc.)

Beta cells in islets of Langerhans in pancreas detect blood glucose concentration is too high → secrete insulin:

Attaches to specific receptors on cell surface membranes of target cells eg. liver / muscles
1. Causing more glucose channel proteins to join cell surface membrane
→ increases permeability to glucose → more glucose enters cell by facilitated diffusion
2. Activating enzymes involved in conversion of glucose to glycogen (glycogenesis)
→ lowers glucose conc. in cells → glucose enters cells by facilitated diffusion down conc. gradient
The action of glucagon (to increase blood glucose conc.)

Alpha cells in islets of Langerhans in pancreas detect blood glucose conc. too low → secrete glucagon:

Attaches to specific receptors on cell surface membranes of target cells eg. liver
1. Activates enzymes involved in hydrolysis of glycogen to glucose (glycogenolysis)
2. Activates enzymes involved in conversion of glycerol / amino acids to glucose (gluconeogenesis)

This establishes a concentration gradient → glucose leaves cells and enters blood by facilitated diffusion

The role of adrenaline (to increase blood glucose conc.)

Fear / stress / exercise → adrenal glands secrete adrenaline:

Attaches to specific receptors on cell surface membranes of target cells eg. liver
● Activates enzymes involved in hydrolysis of glycogen to glucose (glycogenolysis)

This establishes a concentration gradient → glucose leaves cells and enters blood by facilitated diffusion

The second messenger model of adrenaline and glucagon action

Adrenaline / glucagon (‘first messenger’) attach to specific receptors on cell membrane which:

1. Activates enzyme adenylate cyclase (changes shape)

2. Which converts many ATP to many cyclic AMP (cAMP)
3. cAMP acts as the second messenger → activates protein kinase enzymes
4. Protein kinases activates enzymes to break down glycogen to glucose

Advantage of this model: amplifies signal from hormone as each hormone can stimulate production of many
molecules of second messenger (cAMP) which can in turn activate many enzymes for rapid increase in glucose
Diabetes

Higher and uncontrolled blood glucose concentration; higher peaks after meals and remains high

Type I Type II

Cause ● Key point = β cells in islets of
langerhans in pancreas produce
insufficient insulin
● Normally develops in childhood due to
an autoimmune response destroying
β cells of Islets of Langerhans
● Key point = receptor (faulty) loses
responsiveness / sensitivity to insulin
● So fewer glucose transport proteins →
less uptake of glucose → less
conversion of glucose to glycogen
● Risk factor = obesity

Control by ● Injections of insulin (not by mouth as
insulin protein is digested)
● Blood glucose concentration
monitored with biosensors; dose of
insulin matched to glucose intake
● Not normally treated this way
● May use drugs which target insulin
receptors to increase their sensitivity →
more glucose uptake by cells / tissues

Control by ● Eating regularly, control carbohydrate ● Reduced sugar intake (carbs) / low
diet intake eg. those that are broken down glycaemic index → less absorbed
manipulation / absorbed slower ● Reduced fat intake → less glycerol
● To avoid sudden rise in glucose converted to glucose
● More (regular) exercise → uses glucose
/ fats by increasing respiration
● Lose weight → increased sensitivity of
receptors to insulin

Students should be able to evaluate the positions of health advisers (want to reduce risk of type II diabetes due
to health problems caused eg. kidney failure) and the food industry (who want to maximise profit) in relation to
the increased incidence of type II diabetes.
6.4.3 Control of blood water potential

The structure of the nephron

● Nephron = basic structural and functional unit of the kidney (millions in the kidney)
● Associated with each nephron are a network of blood vessels

Role of different parts of the nephron

Part of nephron Function

1. Bowman’s / renal capsule Formation of glomerular filtrate (ultrafiltration)

2. Proximal convoluted tubule Reabsorption of water and glucose (selective reabsorption)

3. Loop of Henle Maintenance of a gradient of sodium ions in the medulla

4. Distal convoluted tubule Reabsorption of water (permeability controlled by ADH)

5. Collecting duct
1. Formation of glomerular filtrate

1. High hydrostatic pressure in glomerulus

● As diameter of afferent arteriole (in) is wider than efferent arteriole (out)
2. Small substances eg. water, glucose, ions, urea forced into glomerular filtrate, filtered by:
a. Pores / fenestrations between capillary endothelial cells
b. Capillary basement membrane
c. Podocytes
3. Large proteins / blood cells remain in blood

2. Reabsorption of glucose and water by the proximal convoluted tubule

Reabsorption of glucose (facilitated diffusion and active transport):

1. Na+ actively transported out of epithelial cells to capillary

2. Na+ moves by facilitated diffusion into epithelial cells down
conc. gradient, bringing glucose against its conc. gradient
3. Glucose moves into capillary by facilitated diffusion down its
concentration gradient

Reabsorption of water:

● Glucose etc. in capillaries lowers water potential

● So water moves by osmosis down a water potential gradient

Selective reabsorption - all glucose/amino acids, most water, some

ions, no urea

Application - in diabetes, not all glucose is reabsorbed:

● Blood glucose conc. too high

● So glucose carrier / cotransporter proteins are saturated / working at maximum rate
3. Maintaining a gradient of sodium ions in the medulla by the loop of Henle

Importance:

● Loop of Henle maintains a gradient of sodium ions in the medulla - conc. Increases further down
● So water potential decreases down the medulla (compared to filtrate in collecting duct)
● So a water potential gradient is maintained between the collecting duct and medulla to
maximise reabsorption of water by osmosis from filtrate

Mechanism (explanation makes sense if start with ascending limb):

1. In the ascending limb:

● Na+ actively transported out (so filtrate conc. decreases)
● Water remains as impermeable to water
→ increases conc. of Na+ in medulla, lowering water potential
2. In the descending limb:
● Water moves out by osmosis then reabsorbed by capillaries (so filtrate conc. increases)
● Na+ ‘recycled’ → diffuses back in

Loop of Henle acts as a countercurrent multiplier (you don’t need to know why - it’s very complicated)

Application: animals needing to conserve water have long loops of Henle (thick medulla)

● More Na+ moved out → Na+ gradient is maintained for longer in medulla
● So water potential gradient is maintained for longer and more water can be reabsorbed from collecting
duct by osmosis

4. Reabsorption of water by the distal convoluted tubule and collecting ducts

● Water moves out of the distal convoluted tubule and

collecting duct by osmosis down a water potential gradient
● Controlled by ADH which increases their permeability
Osmoregulation

Control of water potential of the blood (by negative feedback)

Roles of hypothalamus, posterior pituitary and

antidiuretic hormone (ADH) in osmoregulation

Hypothalamus ● Contains osmoreceptors - detect blood

(in brain) water potential
● Produce ADH (when water potential low)

Posterior ● Secrete ADH into blood

pituitary gland ● Due to signal from hypothalamus

Antidiuretic ● More secreted when blood water

hormone potential too low
(ADH) ● Increases permeability of cells of
collecting duct and DCT to water
● So increases water reabsorption back
into blood
● So decreases volume and increases
concentration of urine produced

How the body responds to a decrease in water potential:

Eg. caused by reduced water intake, increased sweating, increased salt intake

1. In the hypothalamus:
● Osmoreceptors detect decrease in water potential
● So hypothalamus produces more ADH
2. Posterior pituitary gland secretes more ADH into blood
3. ADH attaches to receptors on collecting duct (and distal convoluted tubule):
● Increasing permeability of cells to water (aquaporins join cell surface membrane)
● So more water reabsorbed from DCT / collecting duct by osmosis
4. Urine = smaller volume, more concentrated

How the body responds to an increase in water potential - the opposite

Osmoreceptors → less ADH secreted → decreased permeability → less water reabsorbed →larger volume of
less concentrated urine