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Flashcards in Physiology Kanani II Deck (40):

What are the basic types of skeletal muscle fibre and mention briefly some of their differences.

 Type I: slow twitch fibre that is also slow to fatigue. Contains a high concentration of myoglobin, e.g. soleus muscle
 Type II: fast twitch that also fatigues quickly. They have large reserves of glycogen as an energy source, e.g. extraocular muscles. There are two types of fast- twitch fibre depending on their degree of activity


What is the function of the T tubule system, and where is it located?

This system is an invagination of the sarcolemma (muscle cell membrane). In skeletal muscle, it is located at the junction of the A and I bands. It also lies adjacent to the sarcoplasmic reticulum (SR), so that there is rapid release of Ca2.
It is important for the transmission of the action poten- tial across the myofibril.


List some functional differences between skeletal and cardiac muscle.

- Skeletal muscle is voluntary
- Cardiac muscle contracts spontaneously
- 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
- Note than in both types of muscle, the initial fibre length at rest (preload) also determines the strength of contraction


Draw the action potential curve for the sino atrial (SA) node, and a ventricular myocyte. What is the ionic basis for the shape of the ventricular myocyte action potential?

The ionic fluxes that are responsible for myocyte activation may be divided into a number of phases according to their timing in relation to the curve of the action potential:
 Phase 0: Rapid depolarisation – when threshold is reached (around 60 mV), voltage-gated Na- channels open, permitting the influx of Na.
 Phase 1: Partial repolarisation – this occurs following closure of the voltage-gated Na-channels
 Phase 2: Plateau phase – this may last 200–400 ms. Occurs due to open voltage-gated Ca2 allowing a slow inward current of Ca2 that sustains depolarisation. A persisting outward current of K out that balances the influx of calcium ensures that the membrane potential keeps steady during this plateau phase
 Phase 3: Repolarisation following closure of the Ca2-channels, with continued outflow of K
 Phase 4: Pacemaker potential – spontaneous depolarisation due to the inherent instability of the membrane potential of cardiac myocytes


What is the significance of the ‘plateau phase’ of myocyte depolarisation?

The long plateau phase caused by the slow and sustained influx of Ca2 has two important consequences on myocyte performance:
 Myocytes cannot be stimulated to produce tetanic contractions
 Myocytes are not fatigueable


Why do the pacemaker cells of the heart fire

Pacemaker cells of the SA and AV nodes have unstable membrane potentials that decay spontaneously to pro- duce an action potential without having to be stimu- lated. Other myocytes do exhibit this inherent instability, but to a lesser extent than the pacemaker cells.
This is unlike the ‘standard’ worker myocyte that has a relatively stable membrane. When the membrane potential of the pacemaker cell drifts to about 40 mV from a 60mV starting point, voltage-gated Na- channels open up as the action potential is triggered.
This instability of the membrane potential is caused by the progressive reduction of the membrane’s permea- bility to K. The resulting retention of intracellular K coupled with a continued background inflow of Na and Ca2 leads to a progressive increase in the mem- brane potential until the action potential is triggered.


How does digoxin affect the contractility of the myocyte? What is the mechanism of action?

Digoxin increases the inherent contractility of the myocyte, so that the strength of contraction is higher for any given sarcomere length.
This is a cardiac glycoside that inhibits the cardiac mem- brane Na-K ATPase that normally pumps out Na in exchange for K. Therefore, there is a rise in intracellu- lar Na. This reduces the sodium gradient across the membrane, which in turn slows down the activity of the membrane Ca2-Na pump. In doing so, there is intracellular accumulation of Ca2, leading to increased contractility.


What is the relationship between the strength of contraction and the rate of contraction? Why does this occur?

It is known that increasing the frequency of myocyte contraction also increases the strength of contraction. This is known as the ‘Bowditch effect’. It occurs because at higher frequencies of contraction, there is less time for intracellular Ca2 to be pumped out of the cell between beats. Therefore, there is a progressive accu- mulation of intracellular calcium, leading to improved contractility.


What are the three cell types found in the pancreas’ Islets of Langerhans, and what do they secrete?

a-cells: secrete glucagon
 b-cells: secrete insulin
 d-cells: secrete somatostatin


Other than insulin and glucagon, which other hormones may influence the serum [glucose]?

There are several, but the most important are:
 Catacholamines: epinephrine and norepinephrine
 Glucocorticoids: most important being cortisol
 Somatotrophin: a pituitary hormone
All of the above increase serum [glucose]. The only hormone that is known to decrease serum [glucose] is insulin.


What are the possible metabolic fates for glucose molecules in the body?

Glycolysis: they may be metabolised by glycolysis and then to the tricarboxylic acid (TCA) cycle following the production of pyruvate
 Storage: as glycogen, through the process of glycogenesis. Most tissues of the body are able to do this
 Protein glycosylation: this is a normal process by which proteins are tagged with glucose molecules. This is by strict enzymatic control
 Protein glycation: this is where proteins are tagged with glucose in the presence of excess circulating [glucose]. It is not enzymatically controlled unlike the above example. An example of this is glycosylated haemoglobin
 Sorbitol formation: this occurs in various tissues when glucose enters the polyol pathway that ultimately leads to the formation of fructose from glucose


Where do the body’s glucose molecules come from?

The diet
 Glycogenolysis: following the breakdown of glycogen
 Gluconeogenesis: this is the generation of glucose from non-carbohydrate precursors


Give some examples of non-carbohydrate molecules that can be converted to glucose (by gluconeogenesis). Which tissues may generate glucose in this way?

Lactate, glycerol and some amino acids, such as alanine. The liver is the only tissue that can normally generate glucose in this way. However, during starvation, the kidneys may also perform gluconeogenesis.


What is the pathophysiology of ketosis?

Diabetes mellitus is a state akin to starvation. There is plenty of circulating glucose, but since there is a lack of insulin, the circulating glucose cannot be taken into the cell to be utilised. This leads to increased lipolysis and increased FFA production. Ketone bodies represent readily transportable fatty acids that can be utilised by organs such as the heart and brain. When there is a lack of glucose, improper utilisation of components of the citric acid cycle leads to a continued build up of ketones, leading to metabolic acidosis. The three ketone bodies: acetone, acetoacetate and b-hydroxybutyrate.


You are asked to examine a patient with chronic diabetes mellitus. What may you find on examination?

On examining the skin:
 Necobiosis lipoidica diabeticorum: seen as red-yellow plaques, usually found on the shin. They may ulcerate
 Leg ulcers
 Areas of fat atrophy where insulin is injected
 Skin infections: cellulites, carbuncles, boils or candidiasis
On examining the eyes:
 Diabetic retinopathy on fundal examination  Cataracts
Features of peripheral vascular disease, with ulceration: there may be evidence of limb amputation, or gangrene.
On neurological examination:
 Presence of a peripheral Charcot’s joint
 Features of diabetic neuropathy, such as reduced
sensation and dorsal column function
Features of chronic renal failure: such as skin pigmentation, hypertension, presence of an iatrogenic peripheral arterial fistula in the wrist (for vascular access during haemodialysis).


What type of gland is the pancreas?

It is a mixed endocrine and exocrine gland.


Microscopically, which other organ does the exocrine component of the pancreas resemble?

The parotid salivary gland. The functional unit of the exocrine pancreas is the acinus. Each acinus consists of a group of polygonal acinar cells that lead into a system of secretory ducts.


Roughly, what is the daily volume of pancreatic juice produced?

1–1.5 l daily.


What is the juice basically composed of?

There are two main components to the juice:
 An aqueous component: containing water, bicarbonate and other ions
 An enzymatic component: containing digestive enzymes


What are the most important ions found in the
secretions of the exocrine pancreas?

 HCO3: at basal secretion, pancreatic juice contains more than twice the concentration of bicarbonate ions as the plasma
 Cl: at basal secretion, this is slightly at lower concentration than the plasma
 Na: similar concentration to the plasma
 K: similar concentration to the plasma
 Note that it has a high pH


Why is there a reciprocal relationship between bicarbonate and chloride ions?

This is because the two ions are exchanges at the acinar cell membrane, so that chloride is absorbed into the cell from the lumen of the ducts in exchange for increased bicarbonate output into the secretions.


List the enzymes secreted by the pancreas. Which molecules are they responsible for the digestion of?

 Proelastase  Lipolytic
 Phospholipase A2  Starch digestion:
Note that the proteases are secreted as the inactive zymogen forms that require activation.

How are they activated?
Trypsinogen is activated by enteropeptidase (also called enterokinase) that is secreted by the mucosa of the duodenum. The trypsin released is then able to activate the other enzymes.


Which factors stimulate pancreatic secretion?

Vagal stimulation
 Secretin: a hormone produced by the duodenal mucosa following the appearance of acid. Predominantly stimulates the aqueous component
 CCK: released from the duodenum following the appearance of fatty food
 Gastrin: causes less pronounced stimulation


Taking all of this into account, outline the effects
of a total pancreatectomy.

Development of diabetes mellitus
 Reduced fat absorption: leading to steatorrhoea together with malabsorption of the fat-soluble vitamins A, D, E, and K
 Reduced protein absorption: leading to a negative nitrogen balance
 Reduced absorption of Fe and Ca2: this is due to the loss of alkalinisation of the chyme from the stomach that normally promotes the absorption of these ions. Therefore leads to iron-deficiency anaemia and osteoporosis/rickets


Can you think of why those who have been rendered diabetic by pancreatectomy are very sensitive to exogenous insulin therapy?

This is because there is also an absolute lack of glucagon (also secreted by the pancreatic islets). This hormone normally counteracts insulin and places a negative feed- back on its metabolic effects.


Which ECG changes may you see with hyperkalaemia?

Tall and tented T-waves
 Small P-waves
 Wide QRS complex


Which ECG changes might you see in hypokalaemia?

 Small or inverted T-waves
 Prolonged PR-interval
 S–T segment depression


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 reab- sorbed at the PCT.

What kinds of solute?
The most important are sodium, chloride and potas- sium 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.


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

The Na-K ATPase pump.


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.


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


Once released, what is the effect of ADH on the kidney?

This leads to an increase in the reabsorption of solute- free water by the collecting duct.
Also leads to NaCl reabsorption by the thick ascending limb of Henle. By increasing the concentration of the interstitium around the loop of Henle, this enhances the nephron’s ability to reabsorb water.


Loop of Henle

1. Fluid enters the descending limb of Henle that is isotonic with the plasma. The tubular fluid that leaves the PCT is always isotonic with the plasma
2. The descending limb of Henle is permeable to water (and only slightly permeable to salt and urea. Therefore, water is progressively absorbed down the limb, becoming more and more concentrated (up to 1,200 mOsmol1)
3. The ascending limb of Henle is impermeable to water, but permeable to sodium chloride. There is passive diffusion of NaCl down its concentration gradient, when travelling up the limb. This dilutes the tubular fluid
4. When the thick ascending limb is reached, NaCl is actively pumped out, further diluting the tubular fluid. ADH increases the pumping of NaCl into the interstitium
5. By the time that the tubular fluid reaches the collecting duct, it is hypotonic compared to the interstitium. Therefore, in the presence of ADH (which increases the water-permeability of the collecting duct), water is rapidly reabsorbed
6. By the time that urine is excreted, it has a very high osmolality (up to 1,200 mOsmol1)


If the normal CO at rest is said to be 5–6 Lmin1, what is the output of the right side of the heart?

This is also 5–6Lmin1 since under normal circum- stances; the outputs of both sides of the heart are the same.


PVR and the lung volume

 This shows that at very low lung volumes, the PVR is relatively high, but soon falls following distension of the lungs. After this initial fall, with increasing volumes, the PVR rises again. This rise in the PVR following the initial dip is virtually exponential
 Much of these changes can be explained in terms of the elastic forces generated by the collagen and elastin of the lung parenchyma (see ‘Mechanics of breathing IV’). At increasing lung volumes, the elastic recoil forces of the lung increase. This produces a circumferential radial traction force that pulls small airways (i.e. those without cartilaginous walls) and blood vessels open; thus reducing their resistance to the flow of air and blood respectively
 At very small lung volumes, due to little radial traction, pulmonary vessels are collapsed. This has the effect of increasing the overall PVR
 As the lung expands, radial traction forces on the blood vessels increase, increasing their calibre. This causes a progressive fall in the PVR
 At increasing volumes, radial traction overstretches the pulmonary vessels, reducing their calibre. Thus, once again, the PVR rises, and blood flow falls


factors controlling the PVR, and hence the pulmonary blood flow.

 Pulmonary arterial and venous pressure
 Lung volume
 Pulmonary vascular smooth muscle tone: this is affected by various mediators, such as the catacholamines, histamine, 5-HT, and arachidonic acid metabolites
 Hypoxia: this also has an effect on the smooth muscle tone, but is listed separately due to its importance. This leads to pulmonary vasoconstriction, with an increase in the PVR. The result of this is to improve the ventilation-perfusion ratio in the lung in the face of a fall in the PaO2.
It can therefore be considered to be a defence mechanism against the deleterious effects of hypoxia, e.g. in situations of COPD. However, chronic hypoxia, can lead to irreversible pulmonary hypertension with progressive right heart failure (cor pulmonale).


Nitric oxide (NO) is the main method by which many of these mediators act. It is also often used in the management of pulmonary hypertension in the critically ill. What is its mode of action?

 It has a very short duration of action, and functions through stimulation of intracellular Guanylate cyclase, which produces cGMP from GTP. This in turn stimulates cGMP-dependant protein kinases that are involved in causing vessel wall smooth muscle cell relaxation
 Bradykinin and 5-HT are examples of mediators that act through NO


Under normal circumstances, how is the blood flow in the lungs distributed?

 In the standing position, the lowest parts of the lungs receive the greatest blood flow. In fact, a linear decrease in the blood flow distribution can be seen from apex to base
 This is because the hydrostatic pressure of the most dependent portions is greater


How does this alter with exercise?

During mild exercise, the blood flow to the upper and lower portions of the lung increases, but the overall dis- tribution of the flow is more even than during rest.