6- Principles of homeostasis and negative feedback, control of blood glucose levels, RP11, control of blood water potential

Describe 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

Explain the importance of maintaining stable core temperature

• If temperature is too high:

  • hydrogen bonds in tertiary structure of enzymes break

  • enzymes denature; active sites change shape and substrates can’t bind

  • so fewer E-S complexes

• If temperature is too low

  • not enough kinetic energy so fewer E-S complexes

Explain the importance of maintaining stable blood pH

• 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 E-S complexes

Explain the importance of maintaining stable blood glucose concentration - too low (hypoglycaemia)

• not enough glucose (respiratory substrate) for respiration

• so less ATP produced

• active transport etc can’t happen= cell death

Explain the importance of maintaining stable blood glucose concentration - too high (hyperglycaemia)

• water potential of blood decreases

• water lost from tissue to blood via osmosis

• kidneys can’t absorb all glucose= more water lost in urine causing dehydration

Describe the role of negative feedback in homeostasis

1. Receptors detect change from optimum

2. Effectors respond to counteract change

3. Returning levels to optimum/ normal

EXAMPLES: control of blood glucose conc, blood pH, core temperature and blood water potential

Explain the 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)

Describe positive feedback

1. Receptors detect change from normal

2. Effectors respond to amplify change

3. Producing a greater deviation from normal

NOT involved in homeostasis

EXAMPLES: onset of contractions in childbirth, blood clotting

Describe the factors that influence blood glucose concentration

• consumption of carbohydrates= glucose absorbed into blood

• rate of respiration of glucose e.g. increases during exercise due to muscle contraction

Describe the role of the liver in glycogenesis, glycogenolysis and gluconeogenesis

GLYCOGENESIS:

• converts glucose= glycogen

GLYCOGENOLYSIS:

• converts glycogen= glucose

GLUCONEOGENESIS:

• converts amino acids and/ or glycerol= glucose

Explain the action of insulin in decreasing blood glucose concentration

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 e.g. liver/ muscles

1. This causes more glucose channel proteins to join cell surface membrane

   • increasing permeability to glucose

   • so more glucose can enter cell by facilitated diffusion

2. This also activates enzymes involved in conversion of glucose to glycogen (glycogenesis)

   • lowering glucose concentration in cells, creating a concentration gradient

   • so glucose enters cell by facilitated diffusion

Explain the action of glucagon in increasing blood glucose concentration

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

• Attaches to specific receptors on cell surface membranes of target cells e.g. 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 enters blood by facilitated diffusion

Explain the role of adrenaline in increasing blood glucose concentration

Fear/ stress/ exercise= adrenal glands secrete adrenaline:

• Attaches to specific receptors on cell surface membranes of target cells e.g. liver

• Activates enzymes involved in hydrolysis of glycogen to glucose (glycogenolysis)

• This establishes a concentration gradient= glucose enters blood by facilitated diffusion

Describe the second messenger model of adrenaline and glucagon action

Adrenaline/ glucagon (first messengers) 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 activate enzymes to break down glycogen to glucose

Suggest an advantage of the second messenger 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

Compare the causes of types I and II diabetes

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

TYPE I:

• key point= Beta cells in islets of langerhans in pancreas produce insufficient insulin

• normally develops in childhood due to an autoimmune response destroying Beta cells of islets of Langerhans

TYPE II:

• key point= receptor (faulty) loses responsiveness/ sensitivity to insulin (but insulin still produced)

• so fewer glucose transport proteins= less uptake of glucose= less conversion of glucose to glycogen

• risk factor= obesity

Describe how of type I diabetes can be controlled

• Injections of insulin (as pancreas doesn’t produce enough)

• Blood glucose conc monitored with biosensors; dose of insulin matched to glucose intake

• Eat regularly and control carbohydrate intake e.g. those that are broken down/ absorbed slower

  • to avoid sudden rise in glucose

Suggest why insulin can’t be taken as a tablet by mouth

• insulin is a protein

• would be hydrolyses by endopeptidases/ exopeptidases

Describe how of type II diabetes can be controlled

• Not normally treated with insulin injections (as pancreas still produces it) but may use drugs which target insulin receptors to increase their sensitivity

  • to increase glucose uptake by cells/ tissues

• Reduce sugar intake (carbohydrates)/ low glycaemic index= less absorbed

• Reduce fat intake= less glycerol converted to glucose

• More (regular) exercise= uses glucose/ fats by increasing respiration

• Lose weight= increased sensitivity of receptors to insulin

Describe how you can evaluate the positions of health advisers and the food industry in relation to the increased incidence of type II diabetes

Consider both arguments:

• Health advisers aim- reduce risk of type II diabetes due to health problems caused (e.g. kidney failure)

  • so need to reduce obesity as it is a risk factor

• Food industry aim- maximise profit

What is RP11?

Production of a dilution series of a glucose solution and use of colorimetric techniques to produce a calibration curve with which to identify the concentration of glucose in an unknown ‘urine’ sample

RP11- Describe how a calibration curve could be produced for glucose

1. Use distilled water and a glucose solution of unknown concentration to produce a dilution series (of glucose solutions of known concentrations)

2. Heat a set volume of each solution with a set volume of Benedict’s solution

3. Measure absorbance (of light) of each solution using a colorimeter

4. Plot a graph of absorbance (y axis) against concentration of glucose solution (x axis) and draw a line/ curve of best fit

NOTE- the calibration curve will vary e.g. if precipitate was removed before using the colorimeter

RP11- Describe how the concentration of glucose in an unknown ‘urine’ sample can be identified using a calibration curve

1. Perform Benedict’s test on sample using same volumes of solutions used in producing calibration curve

2. Measure absorbance using a colorimeter

3. Absorbance value for ‘urine’ sample read off calibration curve to find associated glucose conc

RP11- Give examples of variables that should be controlled (2 marks)

• volume of sample used

• volume of Benedict’s solution

• temperature of water bath

• time samples were heated for in water bath

RP11- Explain why a high blood glucose conc can cause glucose to be present in the urine of a diabetic person (2 marks)

• not all glucose reabsorbed at proximal convoluted tubule

• as glucose carrier/ cotransporter proteins are saturated/ working at maximum rate

Describe the structure of a nephron

• Nephron= basic structural and functional unit of the kidney (millions in the kidney)

• Associated with each nephron are a network of blood vessels

Summarise the role of different parts of the nephron

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 conoluted tubule= reabsorption of water (permeability controlled by ADH)

5. Collecting duct

Describe the formation of glomerular filtrate

1. High hydrostatic pressure in glomerulus

   • as diameter of afferent arteriole (in) is wider then efferent arteriole (out)

2. Small substances e.g. water, glucose, ions, urea forced into glomerular filtrate, filtered by:

   • pores/ fenestrations between capillary endothelial cells

   • capillary basement membrane

   • podocytes

3. Large proteins/ blood cells remain in blood

Describe the reabsorption of glucose by the proximal convoluted tubule

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

2. Na+ moves by facilitated diffusion into epithelial cells down a conc gradient, bringing glucose against its conc gradient

3. Glucose moves into capillary by facilitated diffusion down its conc gradient

Describe the reabsorption of water by the proximal convoluted tubule

• Glucose etc in capillaries lower water potential

• Water moves by osmosis down a water potential gradient

Describe and explain how features of the cells in the PCT allow the rapid reabsorption of glucose into the blood

• Microvilli/ folded cell-surface membrane= provides a large SA

• Many channel/ carrier proteins= for facilitated diffusion/ co-transport

• Many carrier proteins= for active transport

• Many mitochondria= produce ATP for active transport

• Many ribosomes= produce carrier/ channel proteins

Suggest why glucose is found in the urine of an untreated diabetic person

• Blood glucose conc is too high so not all glucose is reabsorbed at the PCT

• as glucose carrier/ cotransporter proteins are saturated/ working at maximum rate

Explain the importance of maintaining a gradient of socium 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

Describe the role of the loop of Henle in maintaining a gradient of sodium ions in the medulla

1. In the ascending limb:

   • Na+ actively transported out (so filtrate conc decreases)

   • water remains as ascending limb is impermeable to water

   • this increases conc of Na+ in the 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

The loop of Henle act as as a countercurrent multiplier (you don’t need to know why)

Suggest why animals needing to conserve water have long loops of Henle (thick medulla)

• more Na+ moved out= Na+ gradient is maintained for longer in medulla/ higher Na+ conc

• so water potential gradient is maintained for longer

• so more water can be reabsorbed from collecting duct by osmosis

Describe the reabsorption of water by the distal convoluted tubule and collecting ducts

• water moves out of distal convoluted tubule & collecting duct by osmosis down a water potential gradient

• controlled by ADH which increases their permeability

What is osmoregulation?

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

Describe the role of the hypothalamus in osmoregulation

1. Contains osmoreceptors which detect increase OR decrease in blood water potential

2. Produces more ADH when water potential is low OR less ADH when water potential is high

Describe the role of the posterior pituitary gland in osmoregulation

secretes (more/ less) ADH into blood due to signals from the hypothalamus

Describe the role of antidiuretic hormone (ADH) in osmoregulation

1. Attaches to receptors on collecting duct (and distal convoluted tubule)

2. Stimulating addition of channel proteins (aquaporins) into cell-surface membranes

3. So increases permeability of cells of collecting duct and DCT to water

4. So increases water reabsorption from collecting duct/ DCT (back into blood) by osmosis

5. So decreases volume and increases conc of urine produced

The above applies to a decrease in water potential of the blood (e.g. increases sweating, reduced water intake, increased salt intake). The body responds to an increase in water potential in the opposite way (less ADH secreted, less attaches to receptors, less addition of channel proteins, permeability remains low, less water reabsorption, higher volume & increased conc of urine etc)