1. Name some drugs that activate muscarinic cholinoceptors. What are these compounds used for?

These may be of two broad types based on the mechanism of muscarinic activation:

• Through direct stimulation: examples include carbachol, bethanechol and pilocarpine. Bethanechol has been used for the management of postoperative paralytic ileus and urinary retention. Pilocarpine is used for the management of closed angle glaucoma

• Through indirect stimulation: anticholiesterases promote increased cholinergic stimulation by preventing the hydrolysis of ACh at the synapse. Examples include neostigmine and edrophonium (both quaternary ammonium compounds). Note that these agents are used therapeutically for the reversal of neuromuscular (nicotinic cholinoceptors) blockade. However, as a side effect of preventing ACh hydrolysis, they may also increase the activity of muscarinic cholinoceptors, e.g. at autonomic ganglia

2. What physiologic effects does stimulation of muscarinic receptors lead to?

Essentially, there is increased activation of the PNS:

• Cardiac: with negative inotropic and chronotropic effects, with a reduction in the arterial pressure. This latter effect is exacerbated through peripheral vasodilatation

• Increased glandular secretion: such as increased bronchial, salivary and mucosal secretion. Also increased lacrimation

• Increased smooth muscle contraction: such as in the gut and bronchi. Increased bronchial secretions exacerbate the pathologic effects of bronchoconstriction

• Eye changes: see below

3. Outline the effects of muscarinic stimulation in the eye.

Stimulation leads two main parasympathetic effects:

• Contraction of the constrictor pupillae muscle, reducing the size of the pupil. This also has the effect of improving the drainage of the aqueous humour in those with raised intraocular pressure. In this respect, pilocarpine, a muscarinic agonist, has been used for closed angle glaucoma

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1. Apart from the size of the fibres, what are the structural differences between skeletal and cardiac muscle?

structural differences:

• Cardiac cells are mononuclear, skeletal muscle cells are multinuclear

• The cardiac cell (myocyte) nucleus is centrally located, but peripherally located for skeletal cells

• Cardiac muscle fibres are branched, unlike skeletal fibres

• Cardiac cells are connected to one another by intercalated disks. Gap junctions at these discs allow excitation to pass from one cell to another. Therefore, cardiac myocytes contract as a syncitium

• The T tubule system (which spreads the action potential) is larger in cardiac muscle

• In cardiac muscle, such T tubules are located at the Z line. In skeletal muscle, it is located at the junction of the A and I bands

2. List some functional differences between skeletal and cardiac muscle.

• Skeletal muscle is voluntary

• Cardiac muscle contracts spontaneously (myogenic)

• In skeletal muscle, Ca2+ is released from the SR following spread of depolarisation through the T tubule network

• With cardiac muscle, Ca2+ -release from the SR is triggered by Ca2+ that already been released by the SR, and by Ca2+ that has influxed through membrane voltage channels. This is called Ca2+-induced Ca2+release

• Mechanical summation and tetanus do not occur with cardiac muscle because of the longer duration of cardiac action potential

• In the case of skeletal muscle, increases in force are generated by recruitment of motor units and mechanical summation (see ‘Skeletal muscle’)

• The force of cardiac muscle contraction is determined by the amount of intracellular Ca2+ generated. For example through the action of hormones

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1. Describe briefly the sources of gastric innervation.

• Extrinsic supply: from the sympathetic and parasympathetic systems

• Intrinsic supply: from the enteric nervous system

2. What is the autonomic supply?

• Sympathetic: from the coeliac plexus. Reduces gastric motility

• Parasympathetic: from the vagus nerve – causing increased motility

3. What is the storage capacity of the stomach?

1–2L.

4. How does the stomach accommodate this volume without painful distension?

It undergoes the process of receptive relaxation. This is a vagally mediated reflex where the fundus and the body relax when distending with food.

5. Apart from receptive relaxation, name some other important gastric reflexes.

• Peristalsis: the basic electrical rhythm of the stomach generates slow waves that pass from inflow to outflow segments, propelling food

• Retropulsion: when chyme is pushed backwards and forwards in the lumen. This helps to break up boluses

• Emptying

• Vomiting reflex

6. List the hormones which stimulate gastric emptying.

• Gastrin: released from the gastric G-cells

• CCK: from the duodenum

• Secretin: also from the duodenum

7. What happens to the stomach during the process of vomiting? Outline the steps.

• The process begins with a deep inspiration

• This is followed by closure of the glottis

• There is diffuse contraction of the abdominal and thoracic muscles. This elevates the pressures of both compartments. The intra-abdominal pressure may rise to 800 mm Hg

• Simultaneously, there is relaxation of the lower oesophageal sphincter

• There is a large retrograde contraction of the stomach, forcing the contents into the oesophagus following relaxation of the cricopharyngeus muscle

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1. Where do the coronary arteries originate?

Both the right and left coronary arteries arise directly from the ascending aorta at the aortic sinuses located just above the leaflets of the aortic valve (also known as the sinuses of Valsalva).

2. What is the rate of coronary flow at rest?

70–80 ml/min per 100 g of cardiac tissue. During exercise, this can increase to 300–400 ml/min per 100 g.

3. What percentage of the CO does the heart receive?

4–5%.

4. Given that there is a high myocardial oxygen demand at rest, what functional adaptations ensure that supply meets demand?

Note that the myocardial oxygen consumption is in the order of 8ml per 100 g of tissue. This is around 20 times that of skeletal muscle. Functional adaptations to ensure adequate oxygen delivery include:

• High capillary density: producing a very high surface area for oxygen delivery, and there is high blood flow per unit weight of myocardium

• High oxygen extraction ratio: the myocardium extracts around 70% of the oxygen that is delivered to it from the coronary flow. In contrast, the body average is only 25%

• Efficient metabolic hyperaemia: myocardial metabolites generated during situations of increased exercise and oxygen demand have a strong influence on control of blood flow

• During exercise, the increased oxygen demand is met predominantly through an increase in the rate of flow rather than an increase in the oxygen extraction ratio

5. Look at the graph below, showing the pattern of coronary flow during different phases of the cardiac cycle.

1. What is the principle function of the proximal convoluted tubule (PCT)?

This structure is the kidney's major site for reabsorption of solutes – in fact, 70% of filtered solutes are reabsorbed at the PCT.

2. What kinds of solute?

The most important are sodium, chloride and potassium ions. In addition, nearly all of the glucose and amino acids filtered by the glomerulus are reabsorbed here.

The first half of the PCT also absorbs phosphate and lactate.

3. Which membrane pump system is key to the PCT reabsorptive abilities?

The Na+-K+ ATPase pump.

4. What are the basic functions of the loop of Henle?

• Solute reabsorption: about 20% of filtered sodium, chloride and potassium ions are absorbed in the thick ascending limb of Henle

• Water reabsorption: about 20% of filtered water is absorbed at the thin descending limb of Henle

• Formation of the counter current multiplication system: this is an efficient way of concentrating the urine over a relatively short distance along the nephron with minimal energy expenditure

5. Why there is no water reabsorption at the ascending limb of Henle?

This portion of the loop of Henle is impermeable to water.

6. What is the basic function of the DCT and collecting duct?

• Reabsorption of solute: about 12% of filtered sodium and potassium are absorbed here

• Secretion: variable amounts of potassium and protons are secreted here

• Reabsorption of water: this occurs only at the most distal portions of the DCT and collecting duct, since the more proximal areas are impermeable to water

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1. What is the FiO2 of atmospheric air?

0.21, since 21% of the atmosphere is made up of oxygen.

2. What is the difference between minute ventilation and alveolar ventilation?

• Minute ventilation is the total volume of air entering the respiratory tree every minute, and is equal to Tidal Volume (TV) × Respiratory Rate

• Alveolar ventilation is the volume of gas entering the alveoli each minute. It takes into account the anatomic dead space. This volume of inspired air does not come into contact with respiratory epithelium. Alveolar ventilation is equal to (TV − Anatomic dead space) × Respiratory rate. In a resting 70 kg adult it is about (0.5 – 0.15) × 12 = 4.2Lmin−1

Thus, the alveolar ventilation is a more accurate measure of the level of ventilation since it takes into account only the volume of gas that interfaces with the respiratory epithelium. It can be seen that if a subject takes rapid, shallow breaths, they will become hypoxaemic despite numerically adequate minute ventilation.

3. What is meant by the oxygen cascade?

This term describes the incremental drops in the pO2 from the atmosphere to the arterial blood.

4. What are the changes in the oxygen cascade?

• Atmospheric air: PO2 = 21 kPa

• Tracheal air: pO2 = 19.8 kPa

• Alveolar gas: pO2 = 14.0 kPa

• Arterial blood gas: pO2 = 13.3 kPa

5. What about the changes in the partial pressure of CO2 along the respiratory tree?

• Atmospheric air: PCO2 = 0.03 kPa

• Alveolar air: PCO2 = 5.3 kPa

• Arterial gas: PCO2 = 5.3 kPa

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1. What kinds of coordinated movements does skeletal muscle contraction lead to?

• Voluntary movement

• Reflexes

• Maintenance of posture

• Repetitive and rhythmical movements, e.g. breathing All of these types of movement are under the control of an integrated motor system.

2. What are the components of the motor system that initiate, coordinate and execute these movements?

The components can be thought of as forming an interactive hierarchy. They consist of:

• Cerebral cortex: consisting of the motor cortex and associated areas

• Subcortical areas: the cerebellum, basal ganglia and brainstem

• Spinal cord: this carries fibres from the cerebral cortex to motoneurones, but is also capable of its own intrinsic reflex activity

• Motoneurones: these form the final common pathway

• Motor units: the functional contractile unit

• Receptors and afferent pathways: these sensory pathways relay information back to the other components, which can in turn adjust movement, e.g. proprioceptive information

3. Where is the motor cortex located?

This is found at the precentral gyrus (Brodmann's area 4). This controls contralateral muscular activity. There is also an associated motor cortex, found in Brodmann's areas 6. This helps control movement on both sides of the body.

4. Where in the spinal cord are cell bodies of the motoneurones located?

These are located in the ventral horns of the spinal cord. They congregate together as motor nuclei in specific parts of this ventral horn depending on whether they supply muscles of the axial or appendicular skeleton, and whether they supply proximal or distal limb muscles.

1. What is the difference between starvation, fasting and cachexia?

• Starvation is a chronic state resulting from inadequate intake of energy

• Fasting is a state of energy deprivation lasting no more than several days

• Cachexia is the state resulting from a chronic deprivation of energy and nutrients irrespective of the adequacy of intake, e.g. in malignant cachexia, there is protein and energy malnutrition even when there is adequate intake of food

2. What is the basic difference between marasmus and kwashiorkor?

• Marasmus is characterised by inadequacy of all nutrients and energy sources

• Kwashiokor is characterised by a lack of protein, but there is some intake of energy sources

3. During a period of fasting, from which source does the body obtain glucose?

From glycogen, found most abundantly in the liver and skeletal muscle.

4. How long does this supply last?

About 24 h.

5. When this supply is exhausted, why doesn't the body become hypoglycaemic?

Because, through gluconeogenesis, the liver is able to convert some molecules into glucose.

6. What are the substrates for gluconeogenesis?

• Glycerol: which is released from the breakdown of triglycerides

• Amino acids: from the so-called glucogenic amino acids, such as alanine

• Lactate: production of which is increased following fasting and starvation

7. What is the result of fasting on the body's store of protein and fat?