Lecture 1

How can these results be reconciled?

Which of the following explanations do you regard as being most likely and why?

1. The mode of action of secretin from American dogs is different from that in English dogs.
2. Normally secretin evokes a pancreatic secretion rich in enzymes and in bicarbonate, but the procedure used by the English workers altered its characteristics to such an extent that its enzyme stimulating properties were inhibited
3. The secretin preparation SI in fact contained 2 hormones: secretin and another (now known as CCK-PZ). CCK-PZ stimulates the secretion of enzymes hence the secretion resulting from the SI injection contains enzymes and bicarbonate. M contains only one hormone, secretin, responsible for the production of a secretion rich in bicarbonate but poor in enzymes.
4. M contains two hormones. One of them, secretin, stimulates bicarbonate secretion and another unnamed hormone inhibits the release of enzymes from the pancreas. SI contains only one hormone, secretin, which stimulates the release of both bicarbonate and enzymes from the pancreas.

The most likely explanation of the difference in results is the second which postulates that the procedure used by the English researchers altered the characteristics of the hormone so much to the extent that it inhibited its triggering capacities to lead to production of little enzymes. Usually, secretin triggers the production of pancreatic juices rich in bicarbonate and enzyme (Bayliss and Starling 325-53). The fact the English researchers could not extract a hormone with the same abilities only means that the resulting enzyme had diminished activity as a result of some alteration during extraction (Hacki 609- 32).

 

Lecture 2

How do you think we can measure the resting potential of a neuron?

In a number of cells, the membrane potential is never constant. As it follows, there is never any resting potential and it is usually a theory. However, other cells containing little functions in membrane transport that change less frequently have a resting potential that one can measure by putting or inserting an electrode inside the cell. One can also measure the potential optically using dyes that alter their colours according to the potential of the membrane.

Draw a simple diagram to illustrate your explanation.

(Caldwell and Keynes 12-13).

What is the typical value of the resting potential of a neuron (give units)?

The resting potential of a neuron has a typical value of between -70 millivolts to -80 millivolts (Wright 139- 142).

The charged particles that are responsible for the RMP are called ions:

• The positive ion is called the potassium and sodium ions
• The negative ion is called the p-, chloride ions

 

Generation of the Resting Membrane Potential

 

1. Effect of K+ on the RMP

P-

ECF

ICF

K+

P-

Concentration gradient for K+

K+

 

• Label the concentration gradient for movement of K⁺ across the membrane
• What happens to the P^–? Label this on the diagram.
• A potential will now exist across the membrane: label this on the diagram.
• Label the electrical gradient for movement of K+ across the membrane.

1. Effect of Na+ on the RMP

ECF

ICF

Na+

Na+

Electrical gradient

Concentration gradient for Na+

 

Cl-

_                                                                           +

Na+

 

• Label the concentration gradient for movement of Na+ across the membrane
• Excess Cl- will be left outside the cell; label the potential difference that now exists across the plasma membrane
• Label the electrical gradient for movement of Na+ across the membrane
• Calculating the equilibrium potential

Calculate the equilibrium potential for K⁺ and Na⁺

E_K = Potassium ion== 26.6 In 0.03

= -40.43

 

E_Na = Sodium ion =

26.6 In 156/13

=26.6 In 12

=26.6 x 1.08

=28.7

1. The real situation: the effect of K+ and Na+ combined:

ECF

ICF

K+

P-

Na+

 

• Label the concentration gradient for K+ (K+ attempts to establish E_K)
• Label the concentration gradient for Na+ (Na+ attempts to establish E_Na

Why is the resulting resting membrane potential of –70mV much closer to E_K than E_Na?

Because Ek is more and tending to drag the resting membrane potential towards itself (Hartline and Colman 25- 35). Even though most membranes are not that permeable to these ions, the resting membrane is usually more permeable to potassium ions than sodium ions (Wright 139- 142).

At the RMP neither K+ nor Na+ is at equilibrium, therefore they will continue to diffuse down their concentration gradients. After a period of time, the RMP would be dissipated.

• How is this prevented in the cell?

The membranes solve this by having an active transport mechanism that actively transports potassium to the inside and sodium ions to the outside. Hence the tendency of these ions to diffuse down the gradient is counterbalanced by the sodium, potassium ion pump, transporting the ions against their concentration gradients (Huxley 479- 95).

 

The Chloride ion (C^l-) is the principal extracellular anion. It has an _ECl of –70mV, which is the same as the RMP

• How is Cl- distributed in the cell?

Chloride ions are usually more concentrated outside the cells or extracellularly. Just like sodium ions. The higher concentration outside cells of sodium ions is usually counterbalanced by the high concentration of chloride ions outside the cell (Zoidi and Dermietzel 137-42).

The concentrations of ions in the ECF compartments of a skeletal muscle fibre are given below:

 

Ion	Concentration (mM/L)
	ECF	ICF
Na+	156	13
Cl–	130	9.5
Ca2+	1	0.1
K+	5	160

 

 

Calculate the equilibrium potentials for each ion:

Sodium ion =

26.6 In 156/13

=26.6 In 12

=26.6 x 1.08

=28.7

Chloride ion=26.6 In 130/9.5

26.6 In 13.7

=30.32

Calcium ion= 26.6 In 10

=26.6

Potassium ion== 26.6 In 0.03

= -40.43

Lecture 3

 

1. What are the primary determinants of serum osmolality?

Sodium salts like bicarbonates and chlorides, urea and glucose.

1. If serum glucose increases, what will happen to serum osmolality?

It increase

1. If serum osmolality increases what will happen to the ICF?

It shifts its fluids towards ECF

1. As fluid shifts out of the ICF and into the ECF, what will happen to the serum?

It becomes more concentrated

1. If water is lost in excess of electrolytes, what will happen to the serum osmolality?

It increases

1. What is the estimated serum osmolality for the above example?

>850mOsm/Kg

1. What is the calculated osmolality for the above example?

855mOsm/Kg

1. How do these figures compare to the laboratory value? Why do you think they are slightly different?

They are higher than the laboratory value. This is because in a laboratory setting the loss of water can be controlled (Estad 1085- 6).

Example Two.

1. If a substance such as mannitol is added to the ECF, what will happen to its osmolality?

It increases

1. If very little enters the ICF, what will happen initially to the osmolality of the ICF?

It will increase

1. There is now a concentration difference between the two compartments. Remember that the two compartments are separated by a semi-permeable membrane that allows the movement of water. In which direction will the water move?

Towards the ECF compartment

1. Can you think of a clinical situation where these properties of mannitol could be life-saving?

In cases wher.............