Vascular Disorders

Final post on the cardiovascular system for this unit! (Is it just me, or did that go by quickly?) In this post I will mainly be focusing on hypertension (a.k.a. high blood pressure), with a tiny little bit at the end on a couple of venous disorders (thrombophlebitis and phlebothrombosis).

Hypertension

Hypertension is, simply put, high blood pressure. Normal blood pressure is around 120/80 mmHg, with a mean arterial pressure somewhere around 95mmHg. (For a bit more information on the terminology, see my earlier post on blood pressure.) This isn't a fixed value- it's pretty normal to have blood pressure slightly higher or lower than these values. If your blood pressure is much higher or lower, however, then you might have some issues.

Another thing we need to take into account is that blood pressure does fluctuate over the course of a day and in response to various stimuli. Increasing or decreasing the blood volume will increase or decrease the blood pressure, respectively. Constriction or relaxation of the arteries (i.e. vasoconstriction/vasodilation), which in turn might be due to the action of the sympathetic nervous system, RAAS system or otherwise, can also increase or decrease blood pressure.

Classifications

Hypertension is generally defined as a blood pressure above 140/90. It can also be further broken down into mild, moderate or severe hypertension (severe being >=180/110), but it's not too important to remember the cutoff values for now (to my understanding they're pretty much just a guide anyway). Hypertension can be further divided into primary/essential/idiopathic hypertension, which has no identifiable cause, and secondary hypertension, which is secondary to some other disorder or condition (pregnancy, renal disorders, endocrine disorders etc.).

Pathophysiology

In primary/essential hypertension, there is arteriolar vasoconstriction for some unknown reason. This causes an increase in peripheral resistance, which increases blood pressure. At the same time, renal blood flow is reduced, causing increased activation of the RAAS pathway and thus an increase in blood pressure. A vicious cycle!

The high blood pressure itself can have damaging effects on the arteries. It can damage the arterial wall, leading to an increased risk of atherosclerosis (see my earlier post on Coronary Artery Disease for more information on atherosclerosis). In addition to this, arteries can harden (become sclerotic) and narrow, and the arterial walls can weaken. Weak arterial walls can lead to aneurysms (bulging out of the arterial wall), which can eventually lead to rupture and haemorrhage. Excessive vasoconstriction or atherosclerosis formation can lead to a loss of blood flow to the organs, which can in turn lead to further complications.

Risk factors

Risk factors for hypertension are pretty similar to risk factors for other diseases discussed so far. Once again, age, gender (again males are more susceptible) and genetics are uncontrollable factors. In addition to these, certain ethnicities may be at greater risk. Controllable risk factors for hypertension include obesity, salt intake, physical inactivity, stress, smoking, alcohol consumption and certain drugs (notably corticosteroids and oral contraceptives).

Diagnosis

Hypertension is usually asymptomatic, which is why it's often known as "the silent killer." It can be detected by measuring blood pressure, which is why having your blood pressure tested every so often can be important.

Treatment

Unfortunately, there is no cure for primary hypertension, and so controlling your blood pressure is a life-long process. Most people with hypertension should aim to keep their blood pressure below 140/90, but if they have diabetes as well (another "enemy to the blood vessels," as my prof says), they should aim to keep their blood pressure below 130/80.

Just like other cardiovascular diseases, treatment involves a mix of drug and non-drug therapies, as well as treating any complications that may arise. (Treating the cause probably also comes into it as well in the case of secondary hypertension.) Drug treatments involve diuretics, sympatholytics (i.e. blockers of various aspects of the sympathetic nervous system, such as β-blockers), calcium channel blockers, inhibitors of the RAAS pathway and vasodilators. Non-drug treatments include dietary changes such as reducing salt intake and ensuring adequate potassium, calcium and magnesium, as well as other lifestyle modifications such as stress management techniques and regular exercise.

Unfortunately, despite our best efforts, some people do not respond very well to treatment. This is known as resistant hypertension, and is defined as persistently elevated blood pressure despite treatment. This is more likely to happen in older people, obese people and people with other contributing factors such as renal disease. In these cases, patients may be on multiple drugs to try and keep their blood pressure under control.

If hypertension is not controlled, organs can be damaged, leading to kidney failure, blindness and so on. Severe hypertension with end organ damage is called malignant hypertension. This is a medical emergency!

Thromboembolic Disease

Now for a last little bit about a couple of issues affecting the veins: thrombophlebitis and phlebothrombosis. They're not quite the same thing, though they are unfortunately pretty easy to mix up.

First things first: thrombophlebitis ends with -itis. If you're sharp, you've probably already figured that this condition involves inflammation- and you're right! Thrombophlebitis is inflammation followed by thrombus formation, and is more common in superficial veins.

Phlebothrombosis is a bit different. It also involves a thrombus, but no inflammation is involved- rather, the thrombus appears to form spontaneously (and you might not even know about it until it starts giving you problems). It is more common in deep veins. A classic example of this is DVT (deep vein thrombosis), the constant threat of long-haul air passengers (*cough*15hrflightbetweenHongKongandToronto*cough*).

There are similarities in the pathogenesis of thrombophlebitis and phlebothrombosis. There are three main factors, known as "Virchow's triad." These factors are slow blood flow (stasis), endothelial injury and hypercoagulability, which can all lead to thrombus formation. If not treated, there might be complications: parts of a thrombus can break off, becoming an embolus, and get lodged somewhere else. A common place for thrombi to become lodged is in the lungs. Make sure to do yo' in-flight exercises, kids!

Oh right, I just said "if not treated" without even saying what the treatments are! Well, prevention is better than cure, so once again, moving around can help, as can special stockings. Otherwise, anticoagulants such as heparin can help, and in more extreme cases, a surgical procedure called a thrombectomy might be required.

That's this topic done! Fingers crossed for the topic test on Thursday now...

Carditis

Carditis, as you might expect from the name, is inflammation of the heart. It can be broken down into pericarditis, myocarditis or endocarditis, depending on what part of the heart is affected. If all of the layers of the heart are affected, then it's called pancarditis. Carditis is often involved in rheumatic fever, infective endocarditis and other conditions.

Rheumatic Fever

Rheumatic fever is actually not a disease, but a symptom of one. Essentially, following an untreated infection by β-haemolytic streptococcus group A (e.g. S. pyogenes), the antibodies that were used to fight the disease might turn around to fight the tissues, causing systemic inflammation that affects the heart and other organs. This inflammatory condition, rheumatic fever, tends to occur mainly in children 5-15 years of age.

Rheumatic fever can be responsible for cardiac lesions. It can cause pericarditis, which may come with effusion of fluid, which in turn may impair cardiac filling. It can also cause myocarditis, which can be definitively diagnosed by Aschoff bodies. Aschoff bodies are granulomas consisting of fibrous tissue, lymphocytes and abnormal macrophages. They are pathognomonic to rheumatic fever-induced myocarditis- that is, they only occur in this particular condition. Finally, rheumatic fever can also cause endocarditis, which is the most common problem.

Endocarditis can result in valvular lesions, which usually result in permanent damage. The mitral valve is the most commonly affected, followed by the aortic valve. Sometimes little wart-like vegetations called verrucae form along the outer edges of the cusps. Valvular lesions often result in stenosis (i.e. valves become stiff and blood doesn't readily move through) or incompetence (valves allow too much backflow of blood). Endocarditis from rheumatic fever can also increase the risk of infective endocarditis, a condition that I'll go into more depth later.

Rheumatic fever can also be responsible for extra-cardiac lesions. In joints, it can cause polyarthritis. This tends to affect larger joints such as the knees and ankles and is fleeting- that is, it moves from place to place. It is also unlikely to cause permanent damage. In the skin, rheumatic fever can cause erythema margninatum, which is a red, non-pruritic (i.e. not itchy) rash with a pale centre, as well as subcutaneous nodules, which are little PAINLESS lumps under the skin. (I've put "painless" in capital letters because soon I'll be introducing you to painful ones in a different condition.) A late sign of rheumatic fever is Sydenham's chorea, characterised by semi-purposeful movements (I *think* that means "involuntary movements that look well-coordinated," but I'm not sure). Sydenham's chorea is a result of lesions in the basal nuclei.

Other manifestations of rheumatic fever include low grade fever, loss of appetite, fatigue, dyspnea, and so on. There are, however, specific criteria to look for when making a diagnosis. First are the five major criteria:

1. Carditis
2. Polyarthritis
3. Erythema marginatum
4. Subcutaneous nodules
5. Sydenham chorea

And a few minor criteria:

• Fever
• Arthralgia
• History of rheumatic fever
• Acute phase reaction (i.e. elevated C-reactive protein, ESR, leukocytosis)
• ECG changes (e.g. increased PR interval)

The Modified Jones Criteria state that you need either two major criteria and evidence of streptococcal infection, OR one major and two minor criteria and evidence of streptococcal infection in order to diagnose rheumatic fever. Evidence of strep infection can be found by taking a titer of antistreptolysin O (ASO) antibodies.

Treatment of rheumatic fever involves treating the streptococcal infection with antibiotics. Long-acting antibiotics might also be used as prophylaxis if someone with an infection hasn't developed rheumatic fever yet. Acute carditis can be treated with aspirin and corticosteroids, and drug and surgery treatments can be used to treat long-term cardiac damage.

Infective Endocarditis

Infective endocarditis is, well, endocarditis due to infection. The most common type of infectious organism involved is bacteria, but fungi and viruses can play a role too. Subacute infective endocarditis is caused by non-virulent bacteria such as S. viridians, whereas acute infective endocarditis is caused by more highly virulent bacteria such as S. aureus.

So how does the bacteria do its damage? Well, usually there's a little bit of damage in the heart first, like a valve lesion. Or maybe there is bacteraemia, or bacteria in the blood. Diseases in which immune function is impaired, like AIDS, can also leave people open to infection.

Just like in rheumatic heart disease (RHD) endocarditis, infective endocarditis can lead to vegetations on the valve cusps. These vegetations are composed of fibrin strands, platelets, other blood cells and microorganisms. They can break away, forming septic emboli which cause infections in other places.

Manifestations of infective endocarditis include more general stuff like fever, malaise, fatigue and anorexia (loss of appetite), but there's some other stuff to look out for too. Roth's spots are retinal haemorrhages and Osler's nodes are PAINFUL, red nodules on hands and feet (again, I capitalised painful in order to distinguish them from the painless subcutaneous nodules of RHD). Septic emboli may also cause complications such as abscesses and organ infarctions. Nasty stuff.

Diagnosis of infective endocarditis can be done by echocardiography to look for valve lesions, as well as blood culture in order to detect the organism. Treatment includes antibiotics as well as other kinds of supportive therapy. Surgical repair may be required if serious.

Pericarditis

Pericarditis, inflammation of the pericardium, can be due to a range of causes. It may follow myocardial infarction (in which case it's called Dressler syndrome), rheumatic fever, renal failure, infection, and so on.

Pericarditis can be categorised in several different ways. It can be acute or chronic, acute being more common. Acute pericarditis can lead to cardiac tamponade (lots of pericardial effusion in a short amount of time), while chronic pericarditis can lead to constrictive pericarditis. Pericarditis can be dry or wet. In dry pericarditis there is a lot of fibrous tissue which causes friction in the heart, while in wet pericarditis there is a lot of effusion. Finally, pericarditis can also be categorised according to the composition of the fluid: serous, purulent, fibrinous or haemorrhagic.

Manifestations of pericarditis include chest pain, tachycardia, palpitations, dyspnea, cough and distended neck veins. If there is a lot of effusion, heart sounds may be faint as they have to travel through more fluid. In dry pericarditis, a "friction rub" may also be heard. If cardiac tamponade is present, pulsus paradoxus can occur. Pulsus paradoxus is when your systolic blood pressure drops by more than 10mmHg during inspiration- pretty nasty.

Pericarditis can be diagnosed by pericardiocentesis (aspiration of fluid from the pericardial space) and analysis of the pericardial fluid, as well as by our friends the chest X-ray and the echocardiogram. It can be treated by pericardiocentesis, as well as antibiotics, steroids or even pericardiectomy (removal of a portion or all of the pericardium).

Myocarditis

Myocarditis is inflammation of the myocardium. Once again, the usual culprits causing this condition are infections (viral being the most common here) and rheumatic fever, along with radiation and toxins such as alcohol. It manifests in chest pain, palpitation and so on. It can be diagnosed with ECG and by looking for cardiac markers in blood tests. As it is usually caused by a virus, there are no specific measures for treating myocarditis. General cardiac supportive therapy might help, though.

Congestive Heart Failure

More stuff about the heart! This time it's about heart failure, or the inability of the heart to pump enough blood around the body.

Causes

Congestive heart failure has both cardiac (i.e. heart-related) or extra-cardiac (i.e. from somewhere other than the heart) causes. Cardiac causes include coronary artery disease, previous myocardial infarction, valvular heart disease and other kinds of heart conditions. Extra-cardiac causes include hypertension, pulmonary disease, renal disease, diabetes and other conditions that place more demands on the cardiovascular system.

Classifications

Congestive heart failure can be classified according to anatomy, function or onset. Anatomical classification can be broken down into right-sided failure, left-sided failure or biventricular (i.e. both ventricles) failure. Functional classifications are systolic dysfunction (i.e. inability of the heart to contract) and diastolic dysfunction (i.e. inability of the heart to relax). Onset can be either acute or chronic.

Pathophysiology

When the heart is unable to pump around sufficient blood, the stroke volume decreases, causing cardiac output to decrease and tissue perfusion to decrease. Also, blood can back up in the veins leading to the heart (hence congestive heart failure). If the right side of the heart fails, then this congestion mainly occurs in the systemic circulation, whereas if the left side of the heart fails, then this congestion mainly occurs in the pulmonary circulation.

Our body has ways of trying to compensate when cardiac output is decreased. Unfortunately, in the case of congestive heart failure, these compensatory mechanisms can often aggravate rather than improve the condition. Two of the main ways that the body attempts to compensate is by activation of the sympathetic nervous system (discussed in more detail here) and by activation of the RAAS (Renin-Angiotensin-Aldosterone System) pathway (discussed in more detail here). Both of these work to try and increase blood pressure, but of course this just puts more work on the heart as it has to pump harder in order to overcome the increased blood pressure. Other ways in which the heart tries to compensate is by growing larger (cardiomegaly), but that also aggravates the problem as the larger heart cells require more oxygen than usual to keep going.

Manifestations

General manifestations of congestive heart failure (CHF) include dyspnea (shortness of breath), fatigue and cough following exertion, as well as tachycardia, pallor and oliguria (lack of urine) due to the compensatory effects of the sympathetic nervous system and RAAS system. Some of the other manifestations of congestive heart failure are more specific to the side that is being affected.

As mentioned earlier, left-sided CHF causes blood to back up in the pulmonary circulation. This causes dyspnea (shortness of breath), orthopnea (shortness of breath even when lying down), paroxysmal nocturnal dyspnea (PND) (shortness of breath during the night), haemoptysis (coughing up blood) and other lovely respiratory symptoms. In acute left-sided CHF, pulmonary oedema can occur.

Right-sided CHF, which is usually caused by left-sided CHF, causes blood to back up in the systemic circulation. This causes dependent oedema (oedema due to gravity- when the patient is standing fluid pools in the legs, when they're lying down it pools in their back), digestive disturbances, hepatomegaly, splenomegaly, ascites (fluid in the abdominal cavity), distended jugular veins and in acute cases, headache and visual disturbances. Aside from left-sided CHF, other conditions can cause right-sided CHF, such as cor pulmonale (chronic lung disease leading to CHF), and other factors such as diseases and valve lesions.

Diagnosis

There are several ways to look at diagnosing heart failure. The most important ones are chest X-ray and echocardiography, which can help to visualise the heart and look for cardiomegaly, valve lesions, wall motion abnormalities and so forth. ECG and cardiac catheterisation may also help in some cases.

Treatment

Just like the other heart diseases examined so far, treatment involves a mixture of drugs, non-drug treatments and treating the cause directly.

Drug treatments include diuretics (stop the body from retaining too much fluid in the blood), inhibitors of the RAAS pathway, β-blockers, vasodilators and positive inotropic agents (i.e. stuff that increases strength of contraction) such as digitalis. Non-drug treatments involve bed rest (during acute condition) with gradual rehabilitation back to normal activity, restricting salt in the diet and surgical treatments such as valve repair and transplantation.

Here's another alphabetic mnemonic for you:

• A is for ACE (angiotensin-converting enzyme) inhibitors, angiotensin receptor blockers and aldosterone antagonists (i.e. RAAS inhibitors)
• B is for bed rest and beta-blockers
• C is for cardiac transplantation
• D is for diet, digitalis, diuretics and dilators

In Children...

Children can get CHF too, unfortunately. In children, it's usually secondary to congenital heart defects. Usually the first sign of CHF is feeding difficulty, followed by failure to thrive (i.e. inability to gain weight), short sleep periods and some respiratory distress. Their heartbeats may also have a "gallop rhythm" (i.e. sound like a horse galloping).

Dysrhythmias and Congenital Heart Defects

Back to Pathophysiology! Yay!

If you've forgotten everything about ECGs and the conducting system of the heart, I suggest re-reading my post about the heartbeat- it covers a lot of the basics on how the heart is meant to function. And that's important, because now we're going to find out what happens when the rhythm is out of whack and you have a dysrythmia (or arrhythmia)!

Dysrhythmias

Causes

There are a lot of causes for dysrhythmias/arrythmias, such as damage to the conduction system, electrolyte disturbances, thyroid disease, infection, drugs and so forth.

Monitoring

The ECG, mentioned in my post about the heartbeat, is pretty much the most important diagnostic tool for detecting arrhythmias. Other options include the Holter monitor, which is a portable ECG that a patient wears for 24 hours. The Holter monitor records continuously over this time period. Another type of portable ECG is the event recorder, which a patient can wear for a longer period of time, but it won't record until the patient presses a button to indicate that something is happening (maybe they are feeling faint, or getting palpitations etc.)

Classifications

Arrythmias can be classified in different ways. They can be classified according to heart rate- tachyarrythmias are above 100 beats/min and bradyarrythmias are below 60 beats/min. They can be classified according to rhythm- regular or irregular. Finally, they can also be classified according to origin- supraventricular or ventricular.

I'm going to take you through a few conduction abnormalities, grouped according to where they occur. Bear in mind that not all of these are necessarily pathologic- pretty much all healthy people have tachycardia when they exercise or are stressed, for example. Also, athletes might have a lower resting heart rate than usual (bradycardia).

• SA Node
• Sinus tachycardia- a regular heartbeat between 100 and 160 beats/min.
• Sinus bradycardia- a regular heartbeat lower than 60 beats/min.
• Sick sinus syndrome- caused by damage to the SA node. Characterised by somewhat irregular alternating tachycardia and bradycardia.
• Atrium
• Premature atrial contractions (PAC)- ectopic beats from irritable atrial muscle cells cause early atrial contraction.
• Atrial flutter- an atrial rate 160-350 beats/min. The ventricles maintain a normal, regular rhythm due to the delay at the AV node.
• Atrial fibrillation- an atrial rate over 350 beats/min that does not show up as a P-wave on the ECG. Ventricles beat slowly and irregularly. There is a risk of thrombosis due to blood pooling in the atria (the atria are not contracting properly and pushing their blood into the ventricles).
• AV Node
• Supraventricular tachycardia- signals from the AV node or above cause the ventricles to beat at 150 beats/min or faster. No P-wave appears on the ECG as it is masked by the many QRS complexes.
• Heart block- delay or stoppage of conduction at AV node or bundle of His
• First degree- PR interval longer than 0.2 seconds (normal 0.12-0.2 seconds). Benign- usually only discovered by coincidence.
• Second degree type 1 (Mobitz 1)/Wenckebach: PR interval becomes progressively longer with every beat until QRS is dropped.
• Second degree type 2 (Mobitz 2): PR interval consistent, but not all QRS waves appear.
• Third degree- complete stoppage of transmission between atria and ventricles, causing atria and ventricles to contract independently. Atria contract at the normal rate- ventricles much slower (30-45 beats/min).
• Ventricles
• Premature ventricular contractions (PVCs)- ectopic beats from ventricular cells, causing early contractions. If there's only one or two it's not an issue, but it's a concern if there's several of them.
• Bundle branch block- conduction defect in any one of the bundle branches. Appears as a wide QRS complex on the ECG.
• Ventricular tachycardia (VT)- ventricles beat very fast. This can be dangerous, as this reduces the time for ventricular filling, in turn reducing stroke volume and cardiac output
• Ventricular fibrillation (VF)- MEDICAL EMERGENCY, requiring CPR, defibrillation and/or IV drugs. Ventricle muscle fibres contract independently and rapidly, so they don't provide enough combined force to eject blood. This leads to zero cardiac output.

Symptoms

Arrythmias can range in severity. They can be asymptomatic, or they can lead to palpitations, dizziness, hypotension, syncope and even cardiac arrest (which I'll talk about in a bit).

Treatment

Just like with angina, it's important to try and treat the cause if you can. This can involve correcting electrolyte disturbances, treating thyroid problems, curing infections and so on. If this can't be done, or if the condition doesn't improve, then there are other things that might help. The β-blockers and calcium channel blockers that I mentioned in my post about coronary artery disease might help, as well as digitalis. Pacemakers can also help in SA nodal disease and heart block. In an emergency, defibrillators can save lives.

Cardiac Arrest

Really bad arrythmias (*cough*ventricular fibrillation*cough*- it's probably not the only one though) can lead to cardiac arrest, which is basically when the heart stops beating. It can be classified into two categories: shockable and non-shockable. This basically just refers to whether you can fix it with a defibrillator or not. Shockable forms of cardiac arrest include ventricular fibrillation, as well as pulseless ventricular tachycardia. Non-shockable forms include pulseless electrical activity, as well as asystole. Asystole is defined as not having a heartbeat for longer than 1 second.

Congenital Heart Defects

Causes

Congenital heart defects are structural defects that develop while the baby is still in utero. These might be due to genetic factors such as chromosomal abnormalities, or due to environmental factors such as infection, alcoholism or diabetes in the mother.

Classifications

Congenital heart defects can be classified according to function or structure. Functional classifications are acyanotic or cyanotic- i.e. do they make the child turn blue due to lack of oxygen? Structural classifications refer to the part of the heart that has been affected. Septal defects affect the septa dividing the left and right sides of the heart, valvular defects affect the valves, vascular defects affect the arteries and veins, and so on.

Treatment

Some congenital heart defects correct themselves spontaneously. If not, surgical repair might be possible. Drug therapy and other supportive measures may also need to be used.

Now let's look at some specific heart defects!

Ventricular Septal Defect

Ventricular septal defect- the so-called "hole in the heart"- is the most common congenital heart defect. As the name implies, it's a hole in the interventricular septum (the wall between the two ventricles). Ventricular septal defect is acyanotic- that is, it doesn't turn babies blue.

Usually blood flows through the hole from left to right, as the left ventricle has a higher pressure. This is also known as a left-to-right shunt. This causes less blood to flow around the systemic circulation and more blood to flow around the pulmonary circulation, which can lead to pulmonary hypertension. Over time, pressure can build up in the right ventricle, and when the pressure here exceeds that of the left ventricle, a right-to-left shunt can develop. This results in Eisenmenger's syndrome, which is cyanotic because a right-to-left shunt is essentially directing deoxygenated blood to the systemic circulation.

Tetralogy of Fallot

The tetralogy of Fallot is a collection of four (tetra = four) structural defects that occur together:

1. Narrowing (stenosis) of the pulmonary valve
2. Thickened right ventricle wall due to the extra effort to pump blood through the narrowed valve
3. Ventricular septal defect
4. Aorta moved a little more to the right so that it is over the "hole in the heart."

Another post down!

Innate and Adaptive Immunity

Yay, my first Immunology post! This one actually covers two lectures so it might be pretty long. Bear with me!

Define and explain the anatomic, physiologic, and cellular aspects of innate immunity

Innate immunity is basically your body's first line of defense. It acts quickly and it acts against a wide variety of things, but one thing it can't do is annihilate specific targets, as that's the job of the adaptive immune system. The innate immune system can, however, aid in activating the adaptive immune system.

The anatomic aspects of innate immunity are pretty easy to visualise- they mainly consist of barriers that physically prevent the pathogen from getting in. It'd be a lot easier for bacteria to infect our tissues if we weren't covered with skin, or didn't have something to line our respiratory and GI tracts. Many of these barriers are lined with mucus, which serves as an extra layer of protection.

Mucus (made up of glycoproteins called mucins) is secreted by goblet cells, which are specialised epithelial cells. This is not, however, the only thing that epithelial cells secrete. They also constitutively (i.e. constantly) secrete lysozymes and defensins, which also help fight off invaders. Lysozymes, which are also secreted in tears and saliva as well as by phagocytes, are enzymes that cleave the peptidoglycans making up the bacterial cell wall. They are more effective against gram-positive bacteria which have their peptidoglycan layer on the outside. Defensins are amphipathic molecules that slot into the bacterial membrane, forming pores which cause liquid to rush in and the bacteria to lyse.

If a pathogen gets through all of this, an inflammatory response takes place. Inflammation is a process in which chemical mediators cause vasodilation and increased vascular permeability, allowing other immune cells to migrate into tissues and do their job. Inflammation is characterised by four main signs: redness, swelling, heat and pain. The redness and heat come from the increased blood flow, the swelling comes from the increased fluid escaping the vessels (due to increased permeability), and the pain comes from swollen tissue pressing on nerves.

Now to talk about the main cells of innate immunity! I've already mentioned the main immune cells in an earlier post, but here's a quick refresher on the cells most important to innate immunity. Neutrophils are pretty much the first ones on the scene, and they help phagocytose (eat) things. Monocytes, which differentiate into macrophages, are even more efficient at eating stuff and they're also pretty good at secreting cytokines (messengers of the immune system). Natural Killer cells are not phagocytic, but they can secrete cytotoxic granules which cause lysis of cells that have been infected with a virus or whatever.

One question that you might have is how the immune system recognises what to kill and what not to kill. Immune system cells, such as macrophages and neutrophils, have a collection of cell surface receptors that can recognise and bind microbes. Sometimes it helps if the bacteria or whatever is first opsonised- that is, coated with other proteins such as antibodies or complement. Once a phagocytic cell figures out what to kill, it begins eating- the bacteria are attached to bits of the membrane that stick out a bit (pseudopodia), and are then ingested to form a phagosome which fuses with a lysosome where the bacteria is ultimately eaten. Finally, digestion products are released from the cell in the process of exocytosis.

Other important proteins to know about include complement, mannose-binding lectin, C-reactive proteins and coagulation factors. Complement, which we'll go into detail later on in the course, has a whole load of roles from killing microbes, to opsonising them, to activating leukocytes. Mannose-binding lectin also helps in opsonisation, as well as in activation of complement. C-reactive proteins, which are secreted by hepatocytes, do pretty much the same. Finally, coagulation factors can help wall off infected tissue.

Describe the nature of the adaptive immune response

In contrast to the innate immune response, the adaptive immune response takes longer to kick in but it can provide a targeted, specific response against particular antigens. By "particular antigens," however, I don't just mean a small handful: the B- and T-cells of our adaptive immune system can in fact respond to a very large number of pathogens. The adaptive immune response is also responsible for memory- that is, our body's ability to "remember" what it's been attacked by in the past and be able to respond more strongly to those pathogens if they appear again.

One thing that's important to note is that the innate and adaptive immune responses are not completely separate, but instead work together to eliminate antigens. For example, some innate immune cells can secrete cytokines when activated, which in turn leads to activation of other cells of the immune system, including adaptive immune cells. Also, antigen-presenting cells, such as dendritic cells, can bring antigens from the infection site and "present" them to T-cells. This allows T-cells to differentiate into the right warriors to do the job.

Compare and contrast innate vs adaptive immunity

I feel like I've already done this throughout the post, but here's a quick summary:

	Innate	Adaptive
Time scale	Immediate	Longer time to act
Receptors	Already encoded in the DNA	Requires rearrangement of DNA
Specificity	Non-specific	Specific
Memory capacity	No memory	Memory

Coronary Artery Disease

This is pretty much the first disease we're going to look at in depth, and it's a biggie because lots of people die of it.

Coronary artery disease is essentially what happens when the coronary arteries (the arteries supplying the heart) get blocked for some reason. I recommend reviewing the anatomy of the heart and the blood supply if you're not familiar. I wrote about it on a previous post, but if you can find diagrams somewhere that's even better.

First, some definitions. Arteriosclerosis is a condition in which the arteries become thick and stiff, causing them to have a narrow lumen and thus decreased blood flow. One common type of arteriosclerosis is atherosclerosis, which is caused by the formation of fatty plaques called atheromas. There are a whole bunch of risk factors for atherosclerosis. Some of these aren't controllable, like genetics, age and gender (males are more likely to suffer than females), whereas others are a bit more controllable, like smoking, having a sedentary lifestyle or having uncontrolled diabetes.

There are four main steps for the progression of atherosclerosis. First, the endothelial layer of the blood vessel is damaged. This is usually really tiny damage- maybe just a few cells torn off by high-pressure blood flowing through. Nevertheless, it still provides a surface for some fatty streaks to adhere, which develops into a fibrous plaque. Plaques slow down the blood flowing through, so that further complications like further plaque formation or thrombus (clot) formation are more likely to occur.

Artery blockage is obviously pretty bad, because it means that areas of the body are being deprived of blood. When the coronary arteries are blocked, as in coronary artery disease, this can lead to angina (chest pain) or myocardial infarction (heart attack). Treatment tends to try and get at the root cause by addressing lifestyle factors- for example, losing weight and quitting smoking. Antihyperlipidemic agents (i.e. drugs that get rid of too many lipids) may also be used.

Coronary artery disease has a range of manifestations. Some people are asymptomatic until they suddenly drop dead. Others may have a range of warning signs, from angina and dysrhythmias (i.e. problems with the heart rhythm) to myocardial infarction. Let's look at angina first.

Angina

Angina pectoris, often simply known as angina, is sudden chest pain due to myocardial ischaemia (i.e. not enough blood flow to the heart muscle). It tends to be felt in the chest and down the left arm. There are two main types of angina: typical (exertional) angina and variant (Prinzmetal's) angina. As you can probably guess from the names, typical angina tends to be brought on by exertion (but not always, as you'll see later) and is caused by obstruction of the coronary arteries by atherosclerosis or whatever, whereas variant angina tends to occur at rest and is caused by vasospasm (constriction of the arteries).

Typical (exertional) angina can be further broken down into stable and unstable typical angina. Stable angina follows the classic pattern of chest pain during exercise which is relieved during rest, whereas unstable angina is more prolonged and can occur during rest. Unstable angina can be differentiated from variant angina by the cause: while both occur at rest, unstable angina is due to a blockage in the arteries whereas variant angina is due to vasospasm.

There are several different treatments for angina. Short-term, rest and organic nitrates might be helpful, especially for stable angina. Antianginal drugs such as slower-acting nitrates, β-blockers, calcium channel blockers and anti-platelet drugs (e.g. small doses of aspirin) might be helpful as well. An important point to note is that β-blockers should be avoided in patients with variant (Prinzmetal's) angina, as these may increase the risk of vasospasm. Instead, calcium channel blockers are the drug of choice. Longer term, the underlying cause of angina, whether that be atherosclerosis or something else, should be treated.

Here's a mnemonic for remembering some of the guidelines for treatment and things to look out for with regards to stable angina, courtesy of the American Heart Association:

• A is for Aspirin and Anti-anginals
• B is for Beta-blocker and Blood pressure
• C is for Cholesterol and Cigarettes
• D is for Diet and Diabetes
• E is for Education and Exercise

Myocardial Infarction

Myocardial infarction, a.k.a. a heart attack, is pretty much angina gone extreme. While angina is chest pain due to reduced blood flow to a certain area, myocardial infarction is necrosis of the heart muscle due to a complete lack of blood flow to an area. Scar tissue later forms in place of the necrotic area, further affecting heart function. Myocardial infarction is caused by complete occlusion of the artery, and can be caused by atherosclerosis (just like angina except now you've got a plaque that's completely shutting off blood flow). It is usually transmural, meaning that it affects the entire thickness of the heart wall, and most commonly affects the left ventricle, which doubly sucks because that's the ventricle pumping blood to most parts of the body.

Myocardial infarction manifests as pain, except this pain is more severe and prolonged than angina. It also does not respond to rest or nitrates. In addition to pain, the patient may also be pale, sweating, short of breath and/or have a low-grade fever.

When someone has a myocardial infarction, obviously the most important thing is to stabilise the patient: time is muscle! After that, other tests can be done to definitively determine whether or not the patient was experiencing a myocardial infarction. Blood tests can be used to detect levels of cardiac enzymes released when heart cells die. The most specific markers are Troponin I and CK-MB (a form of creatine kinase only found in the heart), but there are other less specific markers such as myoglobin (the earliest marker) and AST (aspartic transaminase). Coronary angiography can be used to figure out which vessels are blocked and echocardiogram can be used to find other structural abnormalities.

A whole lot of drugs are employed in order to try and treat an acute myocardial infarction. These include nitrates, beta blockers and antiplatelets, just like for angina. Other drugs include thrombolytics (clot-busters), anticoagulants, ACE (angiotensin-converting enzyme) inhibitors and medications for pain relief. More invasive therapies can also be applied: Percutaneous Coronary Intervention (PCI) includes angiography, angioplasty (inflating a small balloon into the artery to make it expand) and stenting. Coronary artery bypass grafting (CABG), which takes a vessel from another part of the body and uses it to bypass the blockage, may also be used.

Phew! This guy's lectures are long...

Cardiovascular Physiology: Introduction and Review

Now we're onto a new topic- Cardiovascular Disorders!

This first lecture was pretty much a recap of basic anatomy and physiology, which I've pretty much already covered in previous posts. Hence this post is basically just like a table of contents.

• The Circulatory System
• More notes on the circulatory system
• Development of the Heart (see also: Birth)
• Heart and Mediastinum
• Tubes (has some information on blood vessels)
• Patterns of Blood Vessels
• Composition of the Blood
• Cardiac Output and Blood Pressure
• The Heartbeat
• The Vascular System
• Microcirculation and Blood Flow
• Control of Blood Pressure
• Special Circulations and Temperature Regulation

Phew! So glad I don't have to type out the stuff on all of those posts again...