Physiology of Smooth Muscle

Now we're onto the second topic for PHYL3001! (I already feel like I've forgotten everything about electrophysiology...)

Identify the characteristics that distinguish smooth muscle from cardiac and skeletal.

See previous post: Tissues
tl;dr: Smooth muscle is smooth. OMG

Oh wait, there is something else that I need to tell you. The following is apparently a tl;dr version of PHYL2002, which I didn't do. Contractions in all kinds of muscles ultimately result from Ca²⁺ binding to something, but that something is different in smooth muscle compared to the other two types of muscles. In cardiac and skeletal muscle, Ca²⁺ binds to troponin on the actin filament, whereas in smooth muscle, Ca²⁺ binds to calmodulin. This results in a Ca²⁺-calmodulin complex, which can activate myosin light chain kinase (MLCK). MLCK can phosphorylate the light chains in smooth muscle, activating ATPases and causing contraction of smooth muscle.

Define single and multi unit smooth muscle, tonic and phasic contraction for smooth muscle.

Tonic and phasic contractions

Tonic contractions are not rhythmic, whereas phasic contractions are. w00t w00t.

Single-unit smooth muscle

Single-unit smooth muscle all contracts as a single unit due to the presence of gap junctions between the cells (sorta like heart muscle). Some, such as the bladder and small blood vessels, can undergo tonic contractions, whereas others, such as the gut and uterus, can undergo phasic contractions. They often show something called "slow waves" or "basal electrical rhythm," which I will talk about in a bit.

Multi-unit smooth muscle

Multi-unit smooth muscle has discrete motor units that have to be activated separately, like skeletal muscle. These muscles only show tonic contraction. Examples of multi-unit smooth muscle include those in the eye, large blood vessels and airways.

List the receptors activated by the neurotransmitters ACh, NA/Adr, NO and ATP.

• ACh- Muscarinic cholinergic receptors. Causes contraction.
• NA/Adr- Can bind to α-adrenergic receptors to cause contraction, or β-adrenergic receptors to cause relaxation.
• NO- Can bind to guanylyl cyclase to cause relaxation.
• ATP- Can bind to P_2X receptors to cause contraction.

Explain the spontaneous contractions of gut, including the role of gap junctions, ICC, slow waves and action potentials.

As mentioned above, single-unit smooth muscle has gap junctions, making it easier for an action potential in one cell to propagate through to others. I also mentioned the basal electrical activity of this type of smooth muscle. But what sets all this off in the first place?

To my understanding, this is caused by ICCs, or Interstitial Cells of Cajal. They essentially act as the paceemaker cells of the gut. ICCs are located in the mucosa and submucosal plexuses, and are connected to smooth muscle cells via gap junctions. It is these cells that cause the "slow waves" of spontaneous, transient inward currents that are largely carried by Ca²⁺.

Slow waves do not cause contractions on their own. They can, however, cause action potentials if they depolarise the cell past the threshold potential. If the threshold is exceeded for long enough, many action potentials will result, which is good, because in smooth muscle many action potentials are required in order to cause a contraction. Neurotransmitters such as ACh can increase the strength of contraction by depolarising the cell to a larger extent, resulting in the cell spending more time above threshold and thus generating more action potentials. (Adrenaline does the opposite.)

Describe the channels and ions involved in smooth muscle action potentials and the actions of nifedipine/verapamil.

At rest, K_ir (inward rectifying) channels are open as they aren't being blocked by Mg²⁺ (see this post for more information). This allows potassium to move in the direction of its concentration gradient, which happens to be out of the cell.

When the cell depolarises, K_ir channels close. As mentioned in this post, these channels close, rather than open, when the cell becomes depolarised. At the same time, Ca²⁺ channels open, increasing Ca²⁺ inside the cell. As mentioned earlier, this allows Ca²⁺ to bind to calmodulin, activating MLCK and thus causing contraction.

Repolarisation occurs when K_v channels open. (You may also see them denoted as K_dr- delayed rectifier- channels.) This allows K⁺ to rush out and the cell to return to its resting potential.

Explain how some smooth muscle do not show action potentials including the relevant ion channels and ion movements.

Yeah, that's right, not all smooth muscles have action potentials. Airway smooth muscle, vascular muscle and others do not show action potentials, even when electrically stimulated. So I guess we'll all just have to throw out our ideas of "action potential = contraction." Damn.

A lack of action potentials is characteristic of many tonic smooth muscles. They can show graded depolarisations, but not full-on action potentials. This is because their K_v channels open really early- in fact, they open pretty much as soon as the cell depolarises. (There's a shit-ton of different K_v channels, so of course some of them have to be different >_>.) Additionally, these cells have K_Ca channels, or calcium-activated K⁺ channels, which I mentioned here but didn't discuss in any detail whatsoever. As their name suggests, they are K⁺ channels that open in response to an increase in Ca²⁺. Therefore, when depolarisation causes Ca²⁺ to come in, these K_Ca channels also open, increasing efflux of K⁺. All of this prevents the membrane potential from "spiking."

Cardiac Arrythmia

Structure and function of ion channels

See earlier post: Ion Channel Structure and Function

What is cardiac arrythmia?

See earlier post: Dysrhythmias and Congenital Heart Defects

Cardiac Long QT syndrome

Cardiac Long QT syndrome is, simply put, a prolongation of the QT interval. (If you don't know what a QT interval is, see here.) This can be inherited (autosomal dominant inheritance) or acquired, usually from various drugs.

Detecting abnormal electrical conduction- the ECG

See previous post: The Heartbeat

Also I'm not really sure where to put this, but one disorder that was covered in this lecture is Torsade de Pointes. It's basically a really erratic ECG that appears to be "turning around" on itself every so often. Because I'm terrible at describing this, here's the picture copy-pasted from the lecture slides to give you an idea of what I mean:

Torsade de Pointes is responsible for lovely stuff like ventricular fibrillation and sudden death.

Measurement of ion conductance- the patch-clamp technique

See previous post: Single Cell Electrophysiology Techniques

Current research investigating the effects of hypoxia on ion channels

For those of you who saw the lecture, don't panic- we don't need to know any of this in depth! This was mainly to show us the wider context of how different techniques and so on are used. As for those who didn't attend the lecture, I'll spare you the details, aside from that our lecturer's lab found that hypoxia seems to increase the sensitivity of the L-type Ca²⁺ channel to β-adrenergic receptor stimulation (mainly because that's the one sentence that I actually understood of this part). Oh and also myocardial ischaemia/hypoxia increases circulating and local catecholamines, increasing the risk of arrythmia and sudden death. What a cheerful note to finish this post on!

Cardiac Ion Channels and the Heart Beat

Tying in with my PHYL3001 post about ion channels, now you're going to get a bit more context and see how these ion channels operate in the heart!

Normal electrical conduction

See previous post: The Heartbeat.

Morphological/functional classification of cells

There are three main types of cells that you should know about. I'm going to use this as an excuse to make another table, because tables are great (despite Blogger's tendency to want to put around 20 lines of space before tables :P).

Name	Shape	Diameter (μm)	No. of myofibrils	Location	Other
Pacemaker cells	Round or oval	3-9	Reduced no.	SA node and AV node
Conducting cells	Cylindrical	50	Reduced no.	Bundle of His, bundle branches, Purkinje fibres	Many intercellular connections
Contractile cells	Cylindrical	10-15	Abundant	Atria and ventricles	Many intercellular connections, extensive T-tubule system

Characteristics of fast and slow action potentials

There are two kinds of action potentials in the heart: a fast and a slow action potential. The slow action potential is responsible for the pacemaker activity of the pacemaker cells, whereas the fast action potential is responsible for the actual contraction that takes place in the atria and ventricles.

Ionic composition of the fast action potential

Behold, a crudely drawn graph of the fast action potential!

Let's break this down into the different phases (labelled with the different numbers)!

Phase 0: Upstroke and Overshoot

This phase is due to a sharp increase in Na⁺ conductance. A large influx of Na⁺ increases the membrane potential from around -80 to around +20. At the end of this phase, Na⁺ conductance decreases rapidly as the channels close.

Phase 1: Initial Repolarisation

This phase is due to the activation and inactivation of a transient outward K⁺ channel (I *think* this is due to the transient outward rectifiers mentioned in my previous post, though unlike what I've said in my previous post, this is happening at a positive, not at a negative, membrane potential). This transient outward current is also known as I_to. As positive charges are let out of the cell, the membrane potential drops slightly, but this is short-lived due to the rapid inactivation of the channels.

Phase 2: Plateau Phase

This phase is due to L-type (long-acting type) Ca²⁺ channels. These open slowly and close slowly, allowing Ca²⁺ to enter the cell briefly and maintain the positive membrane potential.

Phase 3: Final Repolarisation

This phase is due to delayed rectifier K⁺ channels, which, as I mentioned in my last post, are delayed in opening and allow K⁺ to exit (thus lowering the membrane potential).

Phase 4: Resting Membrane Potential

Finally, we have the action of inward rectifier K⁺ channels, which, as also mentioned in my last post, prevent excessive loss of K⁺. This current is also known as I_KI.

Ionic composition of the slow action potential

I'm going to go through this like I did for the fast action potential: first a graph, and then an explanation of each phase. This will be quicker, however, as the slow AP doesn't have phase 1 or 2.

Phase 0: Upstroke

Unlike in fast APs, Na⁺ is not involved in the slow AP. Instead, this phase is due to slow opening of L-type Ca²⁺ channels.

Phase 3: Repolarisation

Ca²⁺ channels close during this phase. Additionally, the outward potassium current increases during this time.

Phase 4: Max Diastolic Potential

During this phase, the cell has a lower conductance to K⁺ and a higher conductance to Na⁺. This results in a reduction in potassium current and/or a steady inward current of Na⁺. This inward current is also called I_h for some reason. Later on, Ca²⁺ conductance increases. This current is also known as I_Ca(T).

Refractory Periods

Just like other action potentials, the fast and slow action potentials of the heart also have refractory periods. There are two main types of refractory period: the early refractory period (ERP) and relative refractory period (RRP). During the early refractory period, between phase 0 and 3, another stimulus will not be able to set off another action potential. If, however, another stimulus comes along during the RRP, which immediately follows the ERP, early firing of the action potential may result.

Extrinsic influences on fast and slow action potentials

The autonomic system is one of the main extrinsic influences on action potentials. Sympathetic activity increases automaticity in pacemaker cells and contractility in contractile cells, whereas parasympathetic control decreases the rate of firing and conduction velocity. The sympathetic and parasympathetic systems also antagonise each other.

Whew! I find the fast and slow APs a little bit confusing, so hopefully I haven't confused you too much!

Ion Channel Structure and Function

Last post on electrophysiology!

Describe the structure and function of voltage-gated ion channels

Voltage-gated ion channels, as the name suggests, are ion channels that open in response to a specific voltage. Voltage-gated channels are made up of several subunits- usually four α₁-subunits that make up the pore, as well as a few other auxiliary subunits. In K⁺ channels, the auxiliary subunits consist of four cytoplasmic β-subunits. In Na⁺ channels, these are two transmembrane β-subunits. In Ca²⁺ channels, there is an extracellular α₂-subunit, a cytoplasmic β-subunit, and transmembrane γ and δ subunits. These auxiliary subunits may help modulate the gating activity of the channel, but we're still not 100% sure.

Since the α₁-subunits are probably the most important, we're going to focus on them. α₁-subunits have six transmembrane domains, imaginatively named S1 through to S6. S4 also serves as a "voltage sensing domain." Between S5 and S6 lies a P (pore) domain, which contains the selectivity filter (i.e. the thing that lets only the ion you want pass) as well as binding sites for other molecules.

Now let's have a look at how these channels work! As I just mentioned, the S4 region senses changes in voltage. That is because S4 domains are made up of largely positive residues, such as arginine, which are usually balanced out by negative charges on a neighbouring helix. When the cell is depolarised (more positive), however, the positive charge inside the cell repels the helix, pushing it around and up (like a screw). This movement also moves the S6 helices, thus opening the channel.

As the ability to sense voltage is clearly pretty important to a voltage-gated channel, it makes sense that this domain has been well conserved throughout evolution. Rats, fruit flies and electric eels share a lot of the same amino acid residues in their S4 regions.

The other key part of the ion channel is the pore region- i.e. the S5-P-S6 portion. In fact, Streptomyces bacteria only have this portion- they don't have the voltage sensing region. The P region, as mentioned above, contains a selectivity filter. This filter is located near the top of the pore and is quite short and narrow, minimising the distance that the ion in question requires in order to interact with the channel. It is lined with residues that will attract the ion in question (e.g. negative charges to attract positive ions), and the spacing is such that it is only energetically favourable for the right size of ion. Just below the selectivity filter is a water-filled cavity and some charged helix dipoles (negatively charged in potassium channels). As ions of the same charge pass through the channel, the repulsion between ions helps propel them through the channel more rapidly.

So far, what I've said applies mainly to K⁺ channels. Other ion channels are similar, but there are some differences. For example, in Na⁺ and Ca²⁺ channels, the four α₁-subunits are actually joined end-to-end to make a giant α subunit with four domains. Furthermore, each of these domains is slightly different- i.e. these are heterotetramers, not monotetramers like K⁺ channels. As I mentioned in a previous post, Na⁺ channels have inactivation gates, which are located between the third and fourth domains.

Understand the similarities and differences between different classes of ion channels

There are several different classes of ion channels. We're going to focus mainly on K⁺ channels for now.

Delayed outward rectifiers

Delayed outward rectifiers, as their name suggests, are delayed in opening and cause potassium to move outwards. The outward current rises steeply at positive voltages (i.e. as the voltage goes up, flow of positive ions out of the cell also goes up). This is probably where the "rectifier" part comes from.

Transient outward rectifiers

Transient currents, also known as A-type currents, are activated and inactivated over a relatively short time period. They tend to be activated when the membrane potential is very negative, such as during hyperpolarisation.

Ca²⁺-activated K⁺ currents

There doesn't seem to be anything in the lecture about these, so... moving on, I guess?

Inward rectifiers

Inward rectifiers, just like the potassium channels of Streptomyces, only has the S5-P-S6 part. As their name suggests, they control current going into, but not out of the cell. They do this with the help of Mg²⁺. When the inside of the cell is positive, Mg²⁺ is pushed towards the edge of the cell, where it blocks the pore of the ion channel. This prevents intracellular K⁺ from leaving, but allows it to enter from the outside. This is important for preventing excessive loss of K⁺ during repeated and/or lengthy action potentials.

(Note: When the inside of the cell is not positive, Mg²⁺ isn't blocking the channel and thus K⁺ will simply travel in the direction of the concentration gradient during this time. This will become more important when we start talking about smooth muscle.)

Become familiar with the impact of genetic mutations on ion channel function and how this impact membrane potentials and cell function

Ion channels, as hopefully you've realised over the past couple of weeks, are pretty important. Hence, genetic mutations can cause a range of problems, from pain disorders to long QT syndrome (which I'll talk about in one of my posts for PHYL3002). Here are some examples of ion channel problems:

Lambert-Eaton Syndrome

Lambert-Eaton Syndrome is an autoimmune disorder in which antibodies are produced against the S5-S6 region of voltage-gated Ca²⁺ channels. This decreases Ca²⁺ influx, which in turn decreases the amount of ACh released. As ACh is important for muscle contraction, this causes muscle weakness. It mainly affects proximal limb muscles, which can make it difficult to climb stairs, but can also affect respiratory muscles. Lambert-Eaton Syndrome can be treated in three main ways: by decreasing the breakdown of ACh (by using drugs such as pyridostigmine), increasing calcium influx (via 3,4-diaminopyridine) or by using immunosuppressants.

Myotonia

Myotonia is slow or relaxed relaxation after contraction. This manifests as difficulty in releasing grip on tools and so on. Myotonia is sometimes aggravated by cold and vigorous exercise.

There are several different causes of myotonia. Myotonia congenita results from mutations in the CLCN1 gene, causing reduced conductance of chloride. As chloride can't move around and balance out the positive charges, this causes repetitive firing of action potentials. Potassium-aggravated myotonia, or PAM, results from slow inactivation of certain sodium channels, also causing a chain of action potentials after the stimulation stops.

Hyperkalemic Periodic Paralysis (HyperPP)

HyperPP results from a large, persistent Na⁺ current. This causes the cell to lose excitability, resuting in paralysis.

Describe the effect of disruption to ion concentration gradients on membrane potential and cell function

When extracellular calcium is high, sodium channels become more likely to open at higher voltages than usual. Essentially, this means that if you want sodium channels to open, you'll need to depolarise the cell more than usual. This also means that a muscle, for instance, will become less excitable and weaker.

On the other hand, when extracellular calcium is low, muscles can become hyper-excitable and twitch spontaneously.

Drugs for Thromboembolic Disorders

Another post on clotting! This post covers drugs that we can use to treat clotting. I've already touched on some of these drugs before, but this post has a lot more details.

Agents that deplete functional clotting factors

Warfarin

Warfarin, as mentioned here, inhibits the synthesis of prothrombin. But how does it do that? you may ask. The answer lies in the effects of warfarin on vitamin K.

Vitamin K actually exists in a reduced (active) and oxidised (inactive) form. When it is active, it is used as a cofactor in the carboxylation of decarboxyprothrombin, a prothrombin precursor made in the liver. (Yup, precursors of precursors.) This process oxidises vitamin K, thus inactivating it. Vitamin K is then made active again by an enzyme called VKORC1 (Vitamin K Epoxide Reductase Complex 1). Warfarin inhibits this enzyme, thereby preventing the recycling of vitamin K and the formation of prothrombin.

Aside from prothrombin, warfarin also inhibits the production of Factors VII, IX and X by a similar mechanism. All of these factors require around 24 hours to actually be depleted, so while warfarin works long-term, it's not that great if you want an immediate effect. Warfarin is also teratogenic, so it can't be used in pregnancy. Yet another issue with warfarin is that you might go too far in the other direction and cause excess bleeding (though this is a potential issue for most if not all anti-clotting drugs). One good thing about warfarin, however, is that it can be easily reversed in an emergency: you can either give the patient fresh donor plasma with the clotting factors that they need, or you can just give them a shitload of vitamin K.

Heparin

As mentioned here, heparin can block prothrombin from becoming thrombin. It does this by inactivating Factor Xa, which catalyses the formation of thrombin. It can also inactivate thrombin.

Heparin is a glycosaminoglycan (see here if you've forgotten what they are). Like other glycosaminoglycans, it is negatively charged. This allows it to bind to antithrombin III, which is positively-charged due to its high proportion of basic amino acid residues (such as lysine and arginine). When heparin binds to AT III, it actually increases its effectiveness by increasing its affinity for Factor Xa and thrombin. This, in turn, increases the rate of anti-coagulation.

Heparin has a couple of advantages over warfarin in that it can act rapidly and is not teratogenic. Like warfarin and other anticoagulants, it does have a risk of bleeding. One of the disadvantages of heparin is that it cannot be administered orally, otherwise our GI tract would just break it down before it could do its job.

Direct inhibitors of clotting factor enzymatic activity

Dabigatrin

Dabigatrin is a direct inhibitor of thrombin (a.k.a. Factor IIa).

Rivaroxaban

Rivaroxaban is a direct inhibitor of Factor Xa.

Antiplatelet drugs

Aspirin

See here for an explanation on aspirin's anti-thromboxane (and thus anti-platelet) activity.

Clopidogrel

Clopidogrel, once broken down to its active metabolite, can irreversibly block platelet ADP receptors. (As I mentioned in my last post, these are needed to help platelets aggregate and adhere during the clotting process.) A newer drug, called prasugrel, does the same thing, but it doesn't need to be broken down to an active metabolite.

Agents that accelerate clot lysis

As mentioned here, plasmin, produced from plasminogen with the help of tPA (tissue plasminogen activator), can break down a clot. tPA can also be produced as a recombinant protein and administered via IV in order to treat a clot rapidly.

Normal and Abnormal Coagulation

This lecture covers a lot of material that I also wrote about when I was in Canada, which is nice. What is less nice is that it doesn't have a nice little summary slide at the end. Oh well.

Platelets

See earlier post: Composition of the Blood

Structure and Function of Blood Vessels

See earlier post: Tubes

Clot Formation

Clotting factor cascade: Cell injury
Thromboembolic diseases (e.g. DVT): Vascular disorders
Atherosclerosis: Coronary Artery Disease

And now for all the stuff that I haven't covered yet!

Another bad place to get a clot is in your atrium. This might happen due to atrial fibrillation. A clot in your left atrium can be pushed into the systemic circulation, where it might lodge into one of the arteries supplying the brain, ultimately causing a stroke. In fact, atrial fibrillation is one of the leading causes of stroke.

Platelets can also cause clots. Platelets are activated when they come into contact with the damaged arterial wall. When this happens, they release thromboxane A2 (TxA₂) and adenosine diphosphate (ADP). These bind to receptors on other platelets, resulting in platelet aggregation and adhesion. As mentioned here, synthesis of thromboxane from arachidonic acid can be blocked by aspirin.

Clot Removal

While clots are important to stop us from bleeding to death, it's also important that the process can stop at some point. Otherwise, we'd turn into a giant human clot after getting a tiny little wound. One important factor in stopping this process is antithrombin III, or AT III. AT III can bind to thrombin, inactivating it. Another important substance is plasmin, which can break up a clot (as mentioned here).

Coagulation Deficiencies

As you can probably tell, there are a lot of components involved in forming and breaking up clots. If any of these factors are missing, problems can result. Deficiencies in clotting factors and platelets, and/or problems in platelet function, can all increase the risk of bleeding. Deficiencies in "anticoagulant" factors, such as AT III, can increase the risk of clots.

Obesity

In my last post, I wrote about energy balance. In this post, I'm going to write about one of the consequences of energy imbalance: obesity!

Know the definition of obesity

Obesity is defined as being 20% overweight. Being obese increases the risk of many other conditions, such as type 2 diabetes, sleep apnoea and cardiovascular disease.

Be able to describe BMI

BMI, or Body Mass Index, is a simple method used to estimate the amount of body fat. It can be calculated by taking a person's mass in kg and dividing it by their height (in m) squared (i.e. BMI = (mass(kg))/(height(m))^2).

Know the limitations of BMI

One of the limitations of BMI is that it only takes height and weight into account. It also cannot distinguish between muscle mass and body fat. Hence, bodybuilders may be classified as overweight or even obese under the BMI system, despite having very little fat. Alternatively, people who have lost a lot of muscle may be classed as underweight, despite still having a decent amount of fat.

Know the WHO guidelines for BMI

• Underweight: <18.5
• Normal: 18.5-24.9
• Overweight: 25-29.9
• Obese: 30-39.9
• Extreme Obesity: 40+

Know why waist circumference is used when assessing disease risk

Since BMI, as I mentioned above, is imperfect, waist circumference is also used as a kind of "backup" measure. If someone is obese and has a large waistline, they are at a higher disease risk than someone who only has one of those factors.

Know some of the risk factors associated with obesity

As mentioned earlier, obesity can increase the risk of a variety of other conditions, such as type 2 diabetes, hypertension, other cardiovascular problems, and so on.

Be able to describe how changes in energy balance can lead to obesity

Obesity occurs when the amount of energy consumed is greater than the amount of energy expended. As excess energy is generally stored as fat, over a long time this can lead to the accumulation of fat and thus obesity.

Be able to discuss factors leading to obesity

Obesity can result from an overconsumption of food or a lack of energy expenditure. The former can result from eating foods that are too energy dense (see here for a definition of energy density) or increased appetite. Increased appetite also has a variety of potential causes, from genetic predispositions to psychological issues. Energy expenditure might be low if someone doesn't exercise regularly, and/or their NEAT is low.

Be aware of the current levels of obesity in Australia

They're not good- let's just put it that way. In 2012 56% of women and 70% of men over the age of 18 were overweight or obese. Also I remember one of my primary school teachers saying that we were beating the US in terms of obesity, but I can't find a source for that.

Be able to discuss the two misconceptions about obesity

One of the misconceptions about obesity is that it is caused by high fat diets. This isn't true as any macronutrient can be converted into fat, as I will explain shortly.

Another misconception about obesity is that obese people are more likely to have a low BMR, and vice versa. This is also untrue. Obese people have more fat, and all of that fat contributes towards the BMR. Hence, obese people often have a higher BMR.

Know that protein and carbohydrate can be converted to triacylglycerols

Both glucose (from carbohydrates) and amino acids (from proteins) can be converted to Acetyl-CoA, which can then be converted to fatty acids and then into triacylglycerols.

Be able to discuss how weight loss can be achieved.

There are drugs and surgical techniques that can help with weight loss. I've covered surgical interventions here, so let's talk about drugs. Amphetamines were one of the earlier drugs that helped with weight loss due to the way that they suppress appetite, but they can be very addictive. Another drug that is no longer in use for this purpose is sibutramine, which also suppresses appetite, but only for a short time until tolerance occurs. Furthermore, sibutramine can increase blood pressure, making it dangerous. A third drug that can cause weight loss is orlistat, which inhibits lipases in the GI tract and thus reduces the uptake of fats. Unfortunately, this causes unpleasant side effects, as well as deficiencies in lipid-soluble vitamins.

Thankfully, there's another way to achieve weight loss, and it mainly involves taking in fewer calories that you expend. This is easier to do by controlling your diet than exercising more, as unfortunately exercise doesn't really burn that many calories. That's not to say that exercise is useless, however: it's still good for building muscle as well as for general health and wellbeing.

Only two more lectures for this module! They're going to be on weight loss and exercise metabolism, so stay tuned!