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How Your Heart Works

by Carl Bianco, MD

Introduction to How Your Heart Works

Everyone knows that the heart is a vital organ. We cannot live without our heart. However,
when you get right down to it, the heart is just a pump. A complex and important one, yes,
but still just a pump. As with all other pumps it can become clogged, break down and need
repair. This is why it is critical that we know how the heart works. With a little knowledge
about your heart and what is good or bad for it, you can significantly reduce your risk for
heart disease.
Heart disease is the leading cause of death in the United States. Almost 2,000 Americans die
of heart disease each day. That is one death every 44 seconds. The good news is that the
death rate from heart disease has been steadily decreasing. Unfortunately, heart disease still
causes sudden death and many people die before even reaching the hospital.
The heart holds a special place in our collective psyche as well. Of course the heart is
synonymous with love. It has many other associations, too. Here are just a few examples:

have a heart - be merciful

change of heart - change your mind
to know something by heart - memorize something
broken heart - to lose love
heartfelt - deeply felt
have your heart in the right place - to be kind
cry your heart out - to grieve
heavy heart - sadness
have your heart set on - to want something badly
Certainly no other bodily organ elicits this kind of response. When was the last time you had
a heavy pancreas?

How strong are you?

You'd probably be amazed to learn how much force your body's
joints and muscles actually support on a daily basis. This
interactive segment from Discovery takes you inside the body and
explains how much strength your bones and muscles really
possess. Other activities let you explore even more of your body's
systems to see exactly how they move you through your daily life.

In this article, we will look at this important organ so that you can understand exactly what
makes your heart tick.
The heart is a hollow, cone-shaped muscle located between the lungs and behind the
sternum (breastbone). Two-thirds of the heart is located to the left of the midline of the body
and 1/3 is to the right (see Figure 1).

Figure 1
[Please note - Medical illustrations assume that the patient is
facing you so that the right and left correspond to the patient's
right and left. That's why the left and right labels here seem backwards.]

The apex (pointed end) points down and to the left. It is 5 inches (12 cm) long, 3.5 inches (89 cm) wide and 2.5 inches (6 cm) from front to back, and is roughly the size of your fist. The
average weight of a female human heart is 9 ounces and a male's heart is 10.5 ounces. The
heart comprises less than 0.5 percent of the total body weight.
The heart has three layers. The smooth, inside lining of the heart is called the endocardium.
The middle layer of heart muscle is called the myocardium. It is surrounded by a fluid filled
sac call the pericardium.

Heart Sounds
When someone listens to your heart with a stethoscope the sound
is often described as lub-dub lub-dub. The first heart sound (lub) is
caused by the acceleration and deceleration of blood and a
vibration of the heart at the time of the closure of the tricuspid and
mitral valves. The second heart sound (dub) is caused by the
same acceleration and deceleration of blood and vibrations at the
time of closure of the pulmonic and aortic valves.

Chambers and Valves

The heart is divided into four chambers: (see Figure 2)
1.right atrium (RA)
2.right ventricle (RV)
3.left atrium (LA)
4.left ventricle (LV)

Figure 2

Pulse Rates
Everyone's pulse (average heart
rate per minute) changes as we
age. Here is a chart of average
pulse rates at different ages:

Each chamber has a sort of one-way valve at its exit that

prevents blood from flowing backwards. When each
chamber contracts, the valve at its exit opens. When it is
finished contracting, the valve closes so that blood does not
flow backwards.

Age

5.

6 months 130

The tricuspid valve is at the exit of the right atrium.

5. The pulmonary valve is at the exit of the right
ventricle.
5. The mitral valve is at the exit of the left atrium.
5. The aortic valve is at the exit of the left ventricle.

When the heart muscle contracts or beats (called systole),

it pumps blood out of the heart. The heart contracts in two
stages. In the first stage, the right and left atria contract at
the same time, pumping blood to the right and left
ventricles. Then the ventricles contract together to propel
blood out of the heart. Then the heart muscle relaxes
(called diastole) before the next heartbeat. This allows
blood to fill up the heart again.

Pulse

Newborn 130
3 months 140
1 year

120

2 years

115

3 years

100

4 years

100

6 years

100

8 years

90

12 years 85

adult
60 - 100
The right and left sides of the heart have separate
functions. The right side of the heart collects oxygen-poor
blood from the body and pumps it to the lungs where it picks up oxygen and releases carbon
dioxide. The left side of the heart then collects oxygen-rich blood from the lungs and pumps it
to the body so that the cells throughout your body have the oxygen they need to function
properly.
Blood Flow
All blood enters the right side of the heart through two veins: The superior vena cava (SVC)
and the inferior vena cava (IVC) (see figure 3).
The SVC collects blood from the upper half of the body. The IVC collects blood from the
lower half of the body. Blood leaves the SVC and the IVC and enters the right atrium (RA)
(3).
When the RA contracts, the blood goes through the tricuspid valve (4) and into the right
ventricle (RV) (5). When the RV contracts, blood is pumped through the pulmonary valve
(6), into the pulmonary artery (PA) (7) and into the lungs where it picks up oxygen.

Figure 3

Heartbeat, It's a Love

Beat
Why does it happen this way? Because blood returning
from the body is relatively poor in oxygen. It needs to be full
of oxygen before being returned to the body. So the right
side of the heart pumps blood to the lungs first to pick up
oxygen before going to the left side of the heart where it is
returned to the body full of oxygen.

The average heartbeat is 72

times per minute. In the course
of one day it beats over 100,000
times. In one year the heart
beats almost 38 million times,
and by the time you are 70 years
old, on average, it's made it to
2.5 billion beats.

Blood now returns to the heart from the lungs by way of the
pulmonary veins (8) and goes into the left atrium (LA) (9). When the LA contracts, blood
travels through the mitral valve (10) and into the left ventricle (LV) (11). The LV is a very
important chamber that pumps blood through the aortic valve (12) and into the aorta (13).
The aorta is the main artery of the body. It receives all the blood that the heart has pumped
out and distributes it to the rest of the body. The LV has a thicker muscle than any other
heart chamber because it must pump blood to the rest of the body against much higher
pressure in the general circulation (blood pressure).
Here is a recap of what we just discussed. Blood from the body flows:

to the superior and inferior vena cava,

then to the right atrium
through the tricuspid valve
to the right ventricle
through the pulmonic valve
to the pulmonary artery
to the lungs

The blood picks up oxygen in the lungs, and then flows from the lungs:

to the pulmonary veins

to the left atrium
through the mitral valve
to the left ventricle
through the aortic valve
to the aorta
to the body

Electrical System
Have you ever wondered what makes your heart beat? How does it do it automatically, every
second of every minute of every hour of every day?
The answer lies in a special group of cells that have the ability to generate electrical activity
on their own. These cells separate charged particles. Then they spontaneously leak certain
charged particles into the cells. This produces electrical impuses in the pacemaker cells
which spread over the heart, causing it to contract. These cells do this more than once per
second to produce a normal heart beat of 72 beats per minute.
The natural pacemaker of the heart is called the sinoatrial node (SA node). It is located in
the right atrium. The heart also contains specialized fibers that conduct the electrical impulse
from the pacemaker (SA node) to the rest of the heart (see Figure 4).

Figure 4
The electrical impulse leaves the SA node (1) and travels to the right and left atria, causing
them to contract together. This takes .04 seconds. There is now a natural delay to allow the
atria to contract and the ventricles to fill up with blood. The electrical impulse has now
traveled to the atrioventricular node (AV node) (2). The electrical impulse now goes to the
Bundle of His (3), then it divides into the right and left bundle branches (4) where it
rapidly spreads using Purkinje fibers (5) to the muscles of the right and left ventricle,
causing them to contract at the same time.
Any of the electrical tissue in the heart has the ability to be a pacemaker. However, the SA
node generates an electric impulse faster than the other tissue so it is normally in control. If
the SA node should fail, the other parts of the electrical system can take over, although
usually at a slower rate.
Although the pacemaker cells create the electrical impulse that causes the heart to beat,
other nerves can change the rate at which the pacemaker cells fire and the how strongly the
heart contracts. These nerves are part of the autonomic nervous system. The autonomic
nervous system has two parts - The sympathetic nervous system and the parasympathetic
nervous system. The sympathetic nerves increase the heart rate and increase the force of
contraction. The parasympathetic nerves do the opposite.
All this activity produces electrical waves we can measure. The measurement is typically
represented as a graph called an electrocardiogram (EKG). Here is an example of three
heartbeats from an EKG (Figure 5):

Figure 5
Each part of the tracing has a lettered name:
1.P wave - coincides with the spread of electrical activity over the atria and the
beginning of its contraction.
2.QRS complex - coincides with the spread of electrical activity over the ventricles
and the beginning of its contraction.
3.T wave - coincides with the recovery phase of the ventricles.
Electrical system abnormalities can range from minor premature beats (skipped beats) that
do not require treatment, to slow or irregular beats that require an artificial pacemaker.
Blood Supply
Coronary arteries are the ones that we try to keep clear by eating a healthy diet. If coronary
arteries are blocked a heart attack results.
The heart, just like any other organ, requires blood to supply it with oxygen and other
nutrients so that it can do its work. The heart does not extract oxygen and other nutrients
from the blood flowing inside it -- it gets its blood from coronary arteries that eventually carry
blood within the heart muscle. Approximately 4 percent to 5 percent of the blood output of
the heart goes to the coronary arteries (7 ounces/minute or 225 ml/min).
There are two main coronary arteries (figure 6) - The left main coronary artery (1) and the
right coronary artery (2) which arise from the aorta. The left main coronary artery divides
into the left anterior descending branch (3) and the left circumflex arteries (4). Each
artery supplies blood to different parts of the heart muscle and the electrical system.

Figure 6
The heart also has veins that collect oxygen-poor blood from the heart muscle. Most of the
major veins of the heart (great cardiac vein, small cardiac vein, middle cardiac vein, posterior
vein of the left ventricle, and oblique vein of the left atrium) drain into the coronary sinus
which opens into the right atrium.
Coronary artery disease is caused by a blockage in one of the coronary arteries. When a
coronary artery is partially blocked, that artery cannot supply enough blood to the heart
muscle to meet its needs during exertion. When someone with coronary artery disease
exerts himself or herself, it causes chest pain. This is due to lack of blood and oxygen to that
part of the heart muscle and is called angina. If the obstruction worsens (more frequent
angina episodes, with less exertion) a condition called unstable angina can occur. A heart
attack happens when a coronary artery is completely blocked and no blood or oxygen is
getting to the heart muscle served by that artery. This also causes chest pain and causes
death to the heart muscle served by that artery.
For more information on the human heart and related topics, check out the links on the next
page.

States of the Heart

An average heart pumps 2.4 ounces (70 milliliters) per heartbeat.
And, as we already mentioned, an average heartbeat is 72 beats
per minute. Therefore an average heart pumps 1.3 gallons (5
Liters) per minute. In other words it pumps 1,900 gallons (7,200
Liters) per day, almost 700,000 gallons (2,628,000 Liters) per year,
or 48 million gallons (184,086,000 liters) by the time someone is
70 years old. That's not bad for a 10-ounce pump.

Lots More Information

Heart disease
Heart disease is an umbrella term for a number of different diseases affecting the heart.
As of 2007, it is the leading cause of death in the United States,[1][2] England, Canada and
Wales,[3] killing one person every 34 seconds in the United States alone.[4]

Contents
[hide]

1 Types of heart disease

o 1.1 Coronary heart disease
o 1.2 Cardiomyopathy
o 1.3 Cardiovascular disease
o 1.4 Ischaemic heart disease
o 1.5 Heart failure
o 1.6 Hypertensive heart disease
o 1.7 Inflammatory heart disease
o 1.8 Valvular heart disease
2 See also
3 References

4 External links

Types of heart disease

Coronary heart disease
Main article: Coronary heart disease
Over 451,000 Americans die of coronary heart disease every year[5]. In the United
Kingdom, 101,000 deaths annually are due to coronary heart disease[6].
Coronary artery disease is a disease of the artery caused by the accumulation of
atheromatous plaques within the walls of the arteries that supply the myocardium. Angina
pectoris (chest pain) and myocardial infarction (heart attack) are symptoms of and
conditions caused by coronary heart disease.

Cardiomyopathy
Main article: Cardiomyopathy
Cardiomyopathy literally means "heart muscle disease" (Myo= muscle, pathy= disease) It
is the deterioration of the function of the myocardium (i.e., the actual heart muscle) for

any reason. People with cardiomyopathy are often at risk of arrhythmia and/or sudden
cardiac death.

Extrinsic cardiomyopathies - cardiomyopathies where the primary pathology is

outside the myocardium itself. Most cardiomyopathies are extrinsic, because by
far the most common cause of a cardiomyopathy is ischemia. The World Health
Organization calls these specific cardiomyopathies[citation needed]:
o Alcoholic cardiomyopathy
o Coronary artery disease
o Congenital heart disease - see below
o Nutritional diseases affecting the heart
o Ischemic (or ischaemic) cardiomyopathy
o Hypertensive cardiomyopathy
o Valvular cardiomyopathy - see also Valvular heart disease below
o Inflammatory cardiomyopathy - see also Inflammatory heart disease
below
o Cardiomyopathy secondary to a systemic metabolic disease
Intrinsic cardiomyopathies - weakness in the muscle of the heart that is not due to
an identifiable external cause.
o Dilated cardiomyopathy (DCM) - most common form, and one of the
leading indications for heart transplantation. In DCM the heart (especially
the left ventricle) is enlarged and the pumping function is diminished.
o Hypertrophic cardiomyopathy (HCM or HOCM) - genetic disorder caused
by various mutations in genes encoding sarcomeric proteins. In HCM the
heart muscle is thickened, which can obstruct blood flow and prevent the
heart from functioning properly.
o Arrhythmogenic right ventricular cardiomyopathy (ARVC) - arises from
an electrical disturbance of the heart in which heart muscle is replaced by
fibrous scar tissue. The right ventricle is generally most affected.
o Restrictive cardiomyopathy (RCM) - least common cardiomyopathy. The
walls of the ventricles are stiff, but may not be thickened, and resist the
normal filling of the heart with blood. ** Noncompaction Cardiomyopathy
- the left ventricle wall has failed to properly grow from birth and such has
a spongy appearance when viewed during an echocardiogram.

Cardiovascular disease
Main article: Cardiovascular disease
Cardiovascular disease is any of a number of specific diseases that affect the heart itself
and/or the blood vessel system, especially the veins and arteries leading to and from the
heart. Research on disease dimorphism suggests that women who suffer with
cardiovascular disease usually suffer from forms that affect the blood vessels while men
usually suffer from forms that affect the heart muscle itself. Known or associated causes
of cardiovascular disease include diabetes mellitus, hypertension, hyperhomocysteinemia
and hypercholesterolemia.

Types of cardiovascular disease include:

Atherosclerosis

Ischaemic heart disease

Ischaemic heart disease - another disease of the heart itself, characterized by

reduced blood supply to the organ.

Heart failure
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Congestive heart failure (CHF), congestive cardiac failure (CCF) or just heart
failure, is a condition that can result from any structural or functional cardiac disorder
that impairs the ability of the heart to fill with blood or pump a sufficient amount of
blood through the body. It is not to be confused with "cessation of heartbeat", which is
known as asystole, or with cardiac arrest, which is the cessation of normal cardiac
function with subsequent hemodynamic collapse leading to death.[citation needed] Because not
all patients have volume overload at the time of initial or subsequent evaluation, the term
"heart failure" (ICD-9 428.9) is preferred over the older term "congestive heart failure".
[citation needed]

Other related terms include ischemic cardiomyopathy (implying that the cause of heart
failure is coronary artery disease) and dilated cardiomyopathy (which is a description of
echocardiographic findings characteristic of heart failure but which does not suggest any
specific etiology.)
Congestive heart failure exacerbation or decompensated heart failure (DHF) refer to
episodes in which a patient with known chronic heart failure acutely develops symptoms.
Congestive heart failure is often undiagnosed due to a lack of a universally agreed
definition and difficulties in diagnosis, particularly when the condition is considered
"mild". Even with the best therapy, heart failure is associated with an annual mortality of
10%.[1] It is the leading cause of hospitalization in people older than 65.[2]

Contents
[hide]

1 Signs and symptoms

o 1.1 Symptoms
o 1.2 Signs

2 Diagnosis
o 2.1 Imaging
o 2.2 Electrophysiology
o 2.3 Blood tests
o 2.4 Angiography
o 2.5 Monitoring
o 2.6 Diagnostic criteria
3 Classification
4 Causes
5 Pathophysiology
o 5.1 Systolic dysfunction
o 5.2 Diastolic dysfunction
6 Treatment
o 6.1 Modalities
6.1.1 Diet and lifestyle measures
6.1.2 Pharmacological management
6.1.2.1 Angiotensin-modulating agents
6.1.2.2 Diuretics
6.1.2.3 Beta blockers
6.1.2.4 Positive inotropes
6.1.2.5 Alternative vasodilators
6.1.2.6 Aldosterone receptor antagonists
6.1.2.7 Recombinant neuroendocrine hormones
6.1.2.8 Vasopressin receptor antagonists
6.1.3 Devices
6.1.4 Surgery
o 6.2 Approach
6.2.1 Acute decompensation
6.2.2 Chronic management
6.2.3 Palliative care and hospice
7 Prognosis
8 References
9 See also

10 External links

Signs and symptoms

Symptoms
Symptoms are dependent on two factors. The first is based on the side of the heart, right
or left, that is involved. The second factor is based on the type of failure, either diastolic
or systolic. Symptoms and presentation may be indistinguishable making diagnosis
impossible based on symptoms.

Given that the left side of the heart pumps blood from the lungs to the organs, failure to
do so leads to congestion of the lung veins and symptoms that reflect this, as well as
reduced supply of blood to the tissues. The predominant respiratory symptom is shortness
of breath on exertion (dyspnea, dyspne d'effort) - or in severe cases at rest - and easy
fatigueability. Orthopnea is increasing breathlessness on reclining, often measured in the
number of pillows required to lie comfortably. Paroxysmal nocturnal dyspnea is a
nighttime attack of severe breathlessness, usually several hours after going to sleep. Poor
circulation to the body leads to dizziness, confusion and diaphoresis and cool extremities
at rest.
The right side of the heart pumps blood returned from the tissues to the lungs to exchange
CO2 for O2. Hence, failure of the right side leads to congestion of peripheral tissues. This
may lead to peripheral edema or anasarca and nocturia (frequent nighttime urination
when the fluid from the legs is returned to the bloodstream). In more severe cases, ascites
(fluid accumulation in the abdominal cavity) and hepatomegaly (painful enlargement of
the liver) may develop.
Heart failure may decompensate easily; this most commonly results from an intercurrent
illness (such as pneumonia), myocardial infarction (a heart attack), arrhythmias,
uncontrolled hypertension, and patient non-compliance with diet or medication.[3] Other
classic precipitating factors are anaemia and hyperthyroidism. These place additional
strain on the heart muscle, which may cause symptoms to rapidly worsen. Excessive fluid
or salt intake (including intravenous fluids for unrelated indications, but more commonly
from dietary indiscretion), and medication that causes fluid retention (such as NSAIDs
and thiazolidinediones), may also precipitate decompensation.[4]

Signs
In examining a patient with possible heart failure, a health professional would look for
particular signs. General signs indicating heart failure are a laterally displaced apex beat
(as the heart is enlarged) and a gallop rhythm (additional heart sounds) in case of
decompensation. Heart murmurs may indicate the presence of valvular heart disease,
either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart
failure.
Predominant left-sided clinical signs are tachypnea and increased work of breathing
(signs of respiratory distress not specific to heart failure), rales or crackles, which
suggests the development of pulmonary edema, dullness of the lung fields to percussion
and diminished breath sounds at the bases of the lung, which suggests the development of
a pleural effusion (fluid collection in the pleural cavity) that is transudative in nature, and
cyanosis which suggests hypoxemia, caused by the decreased rate of diffusion of oxygen
from fluid-filled alveoli to the pulmonary capillaries.
Right-sided signs are peripheral edema, ascites and hepatomegaly, an increased jugular
venous pressure, which can be increased further by the hepatojugular reflux, and a
parasternal heave.

Note that the most common cause of right-sided heart failure is left-sided heart failure, so
that patients commonly present with both sets of signs and symptoms.

Diagnosis
Imaging
Echocardiography is commonly used to support a clinical diagnosis of heart failure. This
modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the
heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total
amount of blood at the end of diastole), and the SV in proportion to the EDV, a value
known as the ejection fraction. In pediatrics, the shortening fraction is the preferred
measure of systolic function. Normally, the EF should be between 50% and 70%; in
systolic heart failure, it drops below 40%. Echocardiography can also identify valvular
heart disease and assess the state of the pericardium (the connective tissue sac
surrounding the heart). Echocardiography may also aid in deciding what treatments will
help the patient, such as medication, insertion of an implantable cardioverter-defibrillator
or cardiac resynchronization therapy. Echocardiography can also help determine if acute
myocardial ischemia is the precipitating cause, and may manifest as regional wall motion
abnormalities on echo.
Chest X-rays are frequently used to aid in the diagnosis of CHF. In the compensated
patient, this may show cardiomegaly (visible enlargement of the heart), quantified as the
cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure,
there may be evidence of vascular redistribution ("upper lobe blood diversion" or
"cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial
edema.

Electrophysiology
An electrocardiogram (ECG/EKG) is used to identify arrhythmias, ischemic heart
disease, right and left ventricular hypertrophy, and presence of conduction delay or
abnormalities (e.g. left bundle branch block). An ECG may also definitively diagnose
acute myocardial ischemia (if ST elevation is present)

Blood tests
Blood tests routinely performed include electrolytes (sodium, potassium), measures of
renal function, liver function tests, thyroid function tests, a complete blood count, and
often C-reactive protein if infection is suspected. An elevated B-type natriuretic peptide
(BNP) is a specific test indicative of heart failure. Additionally, BNP can be used to
differentiate between causes of dyspnea due to heart failure from other causes of dyspnea.
If myocardial infarction is suspected, various cardiac markers may be used.

According to a meta-analysis comparing BNP and N-terminal pro-BNP (NTproBNP) in

the diagnosis of heart failure, BNP is a better indicator for heart failure and left
ventricular systolic dysfunction. In groups of symptomatic patients, a diagnostic odds
ratio of 27 for BNP compares with a sensitivity of 85% and specificity of 84% in
detecting heart failure. [5]

Angiography
Heart failure may be the result of coronary artery disease, and its prognosis depends in
part on the ability of the coronary arteries to supply blood to the myocardium (heart
muscle). As a result, coronary catheterization may be used to identify possibilities for
revascularisation through percutaneous coronary intervention or bypass surgery.

Monitoring
Various measures are often used to assess the progress of patients being treated for heart
failure. These include fluid balance (calculation of fluid intake and excretion), monitoring
body weight (which in the shorter term reflects fluid shifts).

Diagnostic criteria
No system of diagnostic criteria has been agreed as the gold standard for heart failure.
Commonly used systems are the "Framingham criteria"[6] (derived from the Framingham
Heart Study), the "Boston criteria",[7] the "Duke criteria",[8] and (in the setting of acute
myocardial infarction) the "Killip class".[9]
Functional classification is generally done by the New York Heart Association Functional
Classification.[10] This score documents severity of symptoms, and can be used to assess
response to treatment. While its use is widespread, the NYHA score is not very
reproducible and doesn't reliably predict the walking distance or exercise tolerance on
formal testing.[11] The classes (I-IV) are:

Class I: no limitation is experienced in any activities; there are no symptoms from

ordinary activities.
Class II: slight, mild limitation of activity; the patient is comfortable at rest or
with mild exertion.
Class III: marked limitation of any activity; the patient is comfortable only at rest.
Class IV: any physical activity brings on discomfort and symptoms occur at rest.

In its 2001 guidelines, the American College of Cardiology/American Heart Association

working group introduced four stages of heart failure:[12]

Stage A: a high risk HF in the future but no structural heart disorder;

Stage B: a structural heart disorder but no symptoms at any stage;
Stage C: previous or current symptoms of heart failure in the context of an
underlying structural heart problem, but managed with medical treatment;

Stage D: advanced disease requiring hospital-based support, a heart transplant or

palliative care.

Classification
There are many different ways to categorize heart failure, including:

the side of the heart involved, (left heart failure versus right heart failure)
whether the abnormality is due to contraction or relaxation of the heart (systolic
dysfunction vs. diastolic dysfunction)
whether the abnormality is due to low cardiac output or high systemic vascular
resistance (low-output heart failure vs. high-output heart failure)
the degree of functional impairment conferred by the abnormality (as in the
NYHA functional classification)

Causes
Causes and contributing factors to congestive heart failure include the following:[12]
Causes of heart failure
Left-sided: hypertension (high Right-sided: pulmonary hypertension (primary pulmonary
blood pressure), aortic and arterial hypertension versus hypoxic vasoconstriction and
mitral valve disease, aortic
capillary destruction due to chronic lung disease),
coarctation
pulmonary or tricuspid valve disease.
May affect both sides: Ischemic heart disease (due to insufficient vascular supply, usually
as a result of coronary artery disease); this may be chronic or due to acute myocardial
infarction (a heart attack), chronic arrhythmias (e.g. atrial fibrillation), cardiomyopathy of
any cause, cardiac fibrosis, chronic severe anemia, thyroid disease (hyperthyroidism and
hypothyroidism. Left sided failure commonly results in right sided failure.)

] Pathophysiology
Heart failure is caused by any condition which reduces the efficiency of the myocardium,
or heart muscle, through damage or overloading. As such, it can be caused by as diverse
an array of conditions as myocardial infarction (in which the heart muscle is starved of
oxygen and dies), hypertension (which increases the force of contraction needed to pump
blood) and amyloidosis (in which protein is deposited in the heart muscle, causing it to
stiffen). Over time these increases in workload will produce changes to the heart itself:

Reduced contractility, or force of contraction, due to overloading of the ventricle.

In health, increased filling of the ventricle results in increased contractility (by the
Frank-Starling law of the heart) and thus a rise in cardiac output. In heart failure
this mechanism fails, as the ventricle is loaded with blood to the point where heart

muscle contraction becomes less efficient. This is due to reduced ability to crosslink actin and myosin filaments in over-stretched heart muscle.[13]
A reduced stroke volume, as a result of a failure of systole, diastole or both.
Increased end systolic volume is usually caused by reduced contractility.
Decreased end diastolic volume results from impaired ventricular filling as
occurs when the compliance of the ventricle falls (i.e. when the walls stiffen).
Reduced spare capacity. As the heart works harder to meet normal metabolic
demands, the amount cardiac output can increase in times of increased oxygen
demand (e.g. exercise) is reduced. This contributes to the exercise intolerance
commonly seen in heart failure.
Increased heart rate, stimulated by increased sympathetic activity in order to
maintain cardiac output. Initially, this helps compensate for heart failure by
maintaining blood pressure and perfusion, but places further strain on the
myocardium, increasing coronary perfusion requirements, which can lead to
worsening of ischemic heart disease. Sympathetic activity may also cause
potentially fatal arrhythmias.
Hypertrophy (an increase in physical size) of the myocardium, caused by the
terminally differentiated heart muscle fibres increasing in size in an attempt to
improve contractility. This may contribute to the increased stiffness and decreased
ability to relax during diastole.
Enlargement of the ventricles, contributing to the enlargement and spherical shape
of the failing heart. The increase in ventricular volume also causes a reduction in
stroke volume due to mechanical and contractile inefficiency.[14]

The general effect is one of reduced cardiac output and increased strain on the heart. This
increases the risk of cardiac arrest (specifically due to ventricular dysrhythmias), and
reduces blood supply to the rest of the body. In chronic disease the reduced cardiac output
causes a number of changes in the rest of the body, some of which are physiological
compensations, some of which are part of the disease process:

Arterial blood pressure falls. This destimulates baroreceptors in the carotid body
and aortic arch which link to the nucleus tractus solitarius. This center in the brain
increases sympathetic activity, releasing catecholamines into the blood stream.
Binding to alpha-1 receptors results in systemic arterial vasoconstriction. This
helps restore blood pressure but also increases the total peripheral resistance,
increasing the workload of the heart. Binding to beta-1 receptors in the
myocardium increases the heart rate and make contractions more forceful, in an
attempt to increase cardiac output. This also, however, increases the amount of
work the heart has to perform.
Increased sympathetic stimulation also causes the hypothalamus to secrete
vasopressin (also known as antidiuretic hormone or ADH), which causes causing
fluid retention at the kidneys. This increases the blood volume and blood pressure.
Reduced perfusion (blood flow) to the kidneys stimulates the release of renin an
enzyme which catalyses the production of the potent vasopressor angiotensin.
Angiotensin and its metabolites cause further vasocontriction, and stimulate

increased secretion of the steroid aldosterone from the adrenal glands. This
promotes salt and fluid retention at the kidneys, also increasing the blood volume.
The chronically high levels of circulating neuroendocrine hormones such as
catecholamines, renin, angiotensin, and aldosterone affects the myocardium
directly, causing structural remodelling of the heart over the long term. Many of
these remodelling effects seem to be mediated by transforming growth factor beta
(TGF-beta), which is a common downstream target of the signal transduction
cascade initiated by catecholamines[15] and angiotensin II[16], and also by
epidermal growth factor (EGF), which is a target of the signaling pathway
activated by aldosterone[17]
Reduced perfusion of skeletal muscle causes atrophy of the muscle fibres. This
can result in weakness, increased fatigueability and decreased peak strength - all
contributing to exercise intolerance.[18]

The increased peripheral resistance and greater blood volume place further strain on the
heart and accelerates the process of damage to the myocardium. Vasoconstriction and
fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts of
the balance of forces in favour of interstitial fluid formation as the increased pressure
forces additional fluid out of the blood, into the tissue. This results in oedema (fluid
build-up) in the tissues. In right-sided heart failure this commonly starts in the ankles
where venous pressure is high due to the effects of gravity (although if the patient is bedridden, fluid accumulation may begin in the sacral region.) It may also occur in the
abdominal cavity, where the fluid build-up is called ascites. In left-sided heart failure
oedema can occur in the lungs - this is called cardiogenic pulmonary oedema. This
reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the
efficiency of gas exchange by increasing the distance between the air and the blood. The
consequences of this are shortness of breath, orthopnoea and paroxysmal nocturnal
dyspnea.
The symptoms of heart failure are largely determined by which side of the heart fails. The
left side pumps blood into the systemic circulation, whilst the right side pumps blood into
the pulmonary circulation. Whilst left-sided heart failure will reduce cardiac output to the
systemic circultion, the initial symptoms often manifest due to effects on the pulmonary
circulation. In systolic dysfunction, the ejection fraction is decreased, leaving an
abnormally elevated volume of blood in the left ventricle. In diastolic dysfunction, enddiastolic ventricular pressure will be high. This increase in volume or pressure backs up
to the left atrium and then to the pulmonary veins. Increased volume or pressure in the
pulmonary veins impairs the normal drainage of the alveoli and favors the flow of fluid
from the capillaries to the lung parenchyma, causing pulmonary edema. This impairs gas
exchange. Thus, left-sided heart failure often presents with respiratory symptoms:
shortness of breath, orthopnea and paroxysmal nocturnal dyspnea.
In severe cardiomyopathy, the effects of decreased cardiac output and poor perfusion
become more apparent, and patients will manifest with cold and clammy extremities,
cyanosis, claudication, generalized weakness, dizziness, and syncope

The resultant hypoxia caused by pulmonary edema causes vasoconstriction in the

pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle
generates far lower pressures than the left ventricle (approximately 20 mmHg versus
around 120 mmHg, respectively, in the healthy individual) but nonetheless generates
cardiac output exactly equal to the left ventricle, this means that a small increase in
pulmonary vascular resistance causes a large increase in amount of work the right
ventricle must perform. However, the main mechanism by which left-sided heart failure
causes right-sided heart failure is actually not well understood. Some theories invoke
mechanisms that are mediated by neurohormonal activation. Mechanical effects may also
contribute. As the left ventricle distends, the intraventricular septum bows into the right
ventricle, decreasing the capacity of the right ventricle.

Systolic dysfunction
Heart failure caused by systolic dysfunction is more readily recognized. It can be
simplistically described as failure of the pump function of the heart. It is characterized by
a decreased ejection fraction (less than 45%). The strength of ventricular contraction is
attenuated and inadequate for creating an adequate stroke volume, resulting in inadequate
cardiac output. In general, this is caused by dysfunction or destruction of cardiac
myocytes or their molecular components. In congenital diseases such as Duchenne
muscular dystrophy, the molecular structure of individual myocytes is affected. Myocytes
and their components can be damaged by inflammation (such as in myocarditis) or by
infiltration (such as in amyloidosis). Toxins and pharmacological agents (such as ethanol,
cocaine, and amphetamines) cause intracellular damage and oxidative stress. The most
common mechanism of damage is ischemia causing infarction and scar formation. After
myocardial infarction, dead myocytes are replaced by scar tissue, deleteriously affecting
the function of the myocardium. On echocardiogram, this is manifest by abnormal or
absent wall motion.
Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and
volumes increase. This is transmitted to the atrium. On the left side of the heart, the
increased pressure is transmitted to the pulmonary vasculature, and the resultant
hydrostatic pressure favors extravassation of fluid into the lung parenchyma, causing
pulmonary edema. On the right side of the heart, the increased pressure is transmitted to
the systemic venous circulation and systemic capillary beds, favoring extravassation of
fluid into the tissues of target organs and extremities, resulting in dependent peripheral
edema.

Diastolic dysfunction
Heart failure caused by diastolic dysfunction is generally described as the failure of the
ventricle to adequately relax and typically denotes a stiffer ventricular wall. This causes
inadequate filling of the ventricle, and therefore results in an inadequate stroke volume.
The failure of ventricular relaxation also results in elevated end-diastolic pressures, and
the end result is identical to the case of systolic dysfunction (pulmonary edema in left
heart failure, peripheral edema in right heart failure.)

Diastolic dysfunction can be caused by processes similar to those that cause systolic
dysfunction, particularly causes that affect cardiac remodeling.
Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic
function is preserved. The patient may be completely asymptomatic at rest. However,
they are exquisitely sensitive to increases in heart rate, and sudden bouts of tachycardia
(which can be caused simply by physiological responses to exertion, fever, or
dehydration, or by pathological tachyarrhythmias such as atrial fibrillation with rapid
ventricular response) may result in flash pulmonary edema. Adequate rate control
(usually with a pharmacological agent that slows down AV conduction such as a calcium
channel blocker or a beta-blocker) is therefore key to preventing decompensation.
Left ventricular diastolic function can be determined through echocardiography by
measurement of various parameters such as the E/A ratio (early-to-atrial left ventricular
filling ratio), the E (early left ventricular filling) deceleration time, and the isovolumic
relaxation time.

Treatment
The treatment of CHF focuses on treating the symptoms and signs of CHF and preventing
the progression of disease. If there is a reversible cause of the heart failure (e.g. infection,
alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, or hypertension), that should be
addressed as well. Treatments include exercise, eating healthy foods, reduction in salty
foods, and abstinence from smoking and drinking alcohol.

Modalities
Diet and lifestyle measures
Patients with CHF are educated to undertake various non-pharmacological measures to
improve symptoms and prognosis. Such measures include:[19]

Moderate physical activity, when symptoms are mild or moderate; or bed rest
when symptoms are severe.
Weight reduction through physical activity and dietary modification, as obesity
is a risk factor for heart failure and left ventricular hypertrophy.
Monitor weight - this is a parameter that can easily be measured at home. Rapid
weight increase is generally due to fluid retention. Weight gain of more than 2
pounds is associated with admission to the hospital for heart failure[20]
Sodium restriction excessive sodium intake may precipitate or exacerbate heart
failure, thus a "no added salt" diet (60100 mmol total daily intake) is
recommended for patients with CHF. More severe restrictions may be required in
severe CHF.
Fluid restriction patients with CHF have a diminished ability to excrete free
water load. Hyponatremia frequently develops in decompensated heart failure due
to the effects of excess circulating neuroendocrine hormones. While the activation

of the renin-angiotensin-aldosterone axis due to decreased renal perfusion

promotes both sodium and water retention, the activation of atrial natriuretic
peptide due to atrial stretch favors sodium excretion, and the activation of
antidiuretic hormone due to peripheral baroreceptors that sense hypotension as
well as due to the activation of the sympathetic nervous system favors water
retention alone, leading to disproportionately more water retention than sodium
retention. The severity of the hyponatremia during an episode of decompensated
heart failure can be predictive of mortality. Generally water intake should be
limited to 1.5 L daily or less in patients with hyponatremia, though fluid
restriction may be beneficial regardless in symptomatic reduction.
Pharmacological management
There is a significant evidencepractice gap in the treatment of CHF; particularly the
underuse of ACE inhibitors and -blockers and aldosterone antagonists which have been
shown to provide mortality benefit.[21] Treatment of CHF aims to relieve symptoms,
maintain a euvolemic state (normal fluid level in the circulatory system), and to improve
prognosis by delaying progression of heart failure and reducing cardiovascular risk.
Drugs used include: diuretic agents, vasodilator agents, positive inotropes, ACE
inhibitors, beta blockers, and aldosterone antagonists (e.g. spironolactone). It should be
noted that while intuitive, increasing heart function with some drugs, such as the positive
inotrope Milrinone, leads to increased mortality.[22][23]
Angiotensin-modulating agents

ACE inhibitor (ACE) therapy is recommended for all patients with systolic heart failure,
irrespective of symptomatic severity or blood pressure.[24][12][25] ACE inhibitors improve
symptoms, decrease mortality and reduce ventricular hypertrophy. Angiotensin II
receptor antagonist therapy (also referred to as AT1-antagonists or angiotensin receptor
blockers), particularly using candesartan, is an acceptable alternative if the patient is
unable to tolerate ACEI therapy.[26][27] ACEIs and ARBs decrease afterload by
antagonizing the vasopressor effect of angiotensin, thereby decreasing the amount of
work the heart must perform. It is also believed that angiotensin directly affects cardiac
remodeling, and blocking its activity can thereby slow the deterioration of cardiac
function.
Diuretics

Diuretic therapy is indicated for relief of congestive symptoms. Several classes are used,
with combinations reserved for severe heart failure:[19]

Loop diuretics (e.g. furosemide, bumetanide) most commonly used class in

CHF, usually for moderate CHF.
Thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, chlorthiazide) may
be useful for mild CHF, but typically used in severe CHF in combination with
loop diuretics, resulting in a synergistic effect.

Potassium-sparing diuretics (e.g. amiloride) used first-line use to correct

hypokalaemia.
o Spironolactone is used as add-on therapy to ACEI plus loop diuretic in
severe CHF.
o Eplerenone is specifically indicated for post-MI reduction of
cardiovascular risk.

If a heart failure patient exhibits a resistance to or poor response to diuretic therapy,

ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid
retention and congestion. The use of such mechanical methods of fluid removal can
produce meaningful clinical benefits in patients with diuretic-resistant heart failure and
may restore responsiveness to conventional doses of diuretics.9
Beta blockers

Until recently (within the last 20 years), -blockers were contraindicated in CHF, owing
to their negative inotropic effect and ability to produce bradycardia effects which
worsen heart failure. However, current guidelines recommend -blocker therapy for
patients with systolic heart failure due to left ventricular systolic dysfunction after
stabilization with diuretic and ACEI therapy, irrespective of symptomatic severity or
blood pressure.[25] As with ACEI therapy, the addition of a -blocker can decrease
mortality and improve left ventricular function. Several -blockers are specifically
indicated for CHF including: bisoprolol, carvedilol, and extended-release metoprolol. The
antagonism of 1 inotropic and chronotropic effects decreases the amount of work the
heart must perform. It is also thought that catecholamines and other sympathomimetics
have an effect on cardiac remodeling, and blocking their activity can slow the
deterioration of cardiac function.
Positive inotropes

Digoxin (a mildly positive inotrope and negative chronotrope), once used as first-line
therapy, is now reserved for control of ventricular rhythm in patients with atrial
fibrillation; or where adequate control is not achieved with an ACEI, a beta blocker and a
loop diuretic.[25] There is no evidence that digoxin reduces mortality in CHF, although
some studies suggest a decreased rate in hospital admissions.[28] It is contraindicated in
cardiac tamponade and restrictive cardiomyopathy.
The inotropic agent dobutamine is advised only in the short-term use of acutely
decompensated heart failure, and has no other uses.[25]
Phosphodiesterase inhibitors such as milrinone are sometimes utilized in severe
cardiomyopathy. The mechanism of action is through the antagonism of adenosine
receptors, resulting in inotropic effects and modest diuretic effects.
Alternative vasodilators

The combination of isosorbide dinitrate/hydralazine is the only vasodilator regimen, other

than ACE inhibitors or angiotensin II receptor antagonists, with proven survival benefits.
This combination appears to be particularly beneficial in CHF patients with an African
American background, who respond less effectively to ACEI therapy.[29][30]
Aldosterone receptor antagonists

The RALES trial[31] showed that the addition of spironolactone can improve mortality,
particularly in severe cardiomyopathy (ejection fraction less than 25%.) The related drug
eplerenone was shown in the EPHESUS trial[32] to have a similar effect, and it is
specifically labelled for use in decompesated heart failure complicating acute myocardial
infarction. While the antagonism of aldosterone will decrease the effects of sodium and
water retention, it is thought that the main mechanism of action is by antagonizing the
deleterious effects of aldosterone on cardiac remodeling.
Recombinant neuroendocrine hormones

Nesiritide, a recombinant form of B-natriuretic peptide, is indicated for use in patients

with acute decompensated heart failure who have dyspnea at rest. Nesiritide promotes
diuresis and natriuresis, thereby ameliorating volume overload. It is thought that, while
BNP is elevated in heart failure, the peptide that is produced is actually dysfunctional or
non-functional and thereby ineffective.
Vasopressin receptor antagonists

Tolvaptan and conivaptan antagonize the effects of antidiuretic hormone (vasopressin),

thereby promoting the specific excretion of free water, directly ameliorating the volume
overloaded state, and counteracting the hyponatremia that occurs due to the release of
neuroendocrine hormones in an attempt to counteract the effects of heart failure. The
EVEREST trial, which utilized tolvaptan, showed that when used in combination with
conventional therapy, many symptoms of acute decompensated heart failure were
significantly improved compared to conventional therapy alone[33] although they found no
difference in mortality and morbidity when compared to conventional therapy.[34].
Devices
Patients with NYHA class III or IV, left ventricular ejection fraction (LVEF) of 35% or
less and a QRS interval of 120 ms or more may benefit from cardiac resynchronization
therapy (CRT; pacing both the left and right ventricles), through implantation of a biventricular pacemaker, or surgical remodeling of the heart. These treatment modalities
may make the patient symptomatically better, improving quality of life and in some trials
have been proven to reduce mortality.
The COMPANION trial demonstrated that CRT improved survival in individuals with
NYHA class III or IV heart failure with a widened QRS complex on an
electrocardiogram.[35] The CARE-HF trial showed that patients receiving CRT and

optimal medical therapy benefited from a 36% reduction in all cause mortality, and a
reduction in cardiovascular-related hospitalization.[36]
Patients with NYHA class II, III or IV, and LVEF of 35% (without a QRS requirement)
may also benefit from an implantable cardioverter-defibrillator (ICD), a device that is
proven to reduce all cause mortality by 23% compared to placebo. This mortality benefit
was observed in patients who were already optimally-managed on drug therapy.[37]
Patients with severe cardiomyopathy are at high risk for sudden cardiac death due to
ventricular dysrhythmias.
Another current treatment involves the use of left ventricular assist devices (LVADs).
LVADs are battery-operated mechanical pump-type devices that are surgically implanted
on the upper part of the abdomen. They take blood from the left ventricle and pump it
through the aorta. LVADs are becoming more common and are often used by patients
who have to wait for heart transplants.
Surgery
The final option, if other measures have failed, is heart transplantation or (temporary or
prolonged) implantation of an artificial heart. These remain the recommended surgical
treatment options. However, the limited number of hearts available for transplantation in
a growing group of candidates, has led to the development of alternative surgical
approaches to heart failure. These commonly involve surgical left ventricular remodeling.
The aim of the procedures is to reduce the ventricle diameter (targeting Laplace's law and
the disease mechanism of heart failure), improve its shape and/or remove non-viable
tissue.[38] These procedures can be performed together with coronary artery bypass
surgery or mitral valve repair.
If heart failure ensues after a myocardial infarction due to scarring and aneurysm
formation, reconstructive surgery may be an option. These aneurysms bulge with every
contraction, making it inefficient. Cooley and coworkers reported the first surgical
treatment of a left ventricular aneurysm in 1958.[39] The used a linear closure after their
excision. In the 1980s, Vincent Dor developed a method using an circular patch stitched
to the inside of the ventricle (the endoventricular circular patch plasty or Dor procedure)
to close the defect after excision.[40] His approach has been modified by others. Today,
this is the preferred method for surgical treatment of incorrectly contracting (dyskinetic)
left ventricle tissue, although a linear closure technique combined with septoplasty might
be equally effective.[41][42] The multicenter RESTORE trial of 1198 participants
demonstrated an increase in ejection fraction from about 30% to 40% with a concomitant
shift in NYHA classes, with an early mortality of 5% and a 5-year survival of 70%.[43] As
of yet, it remains unknown if surgery is superior to optimal medical therapy. The STICH
trial (Surgical Treatment for IschemiC Heart Failure) will examine the role of medical
treatment, coronary artery bypass surgery and left ventricle remodeling surgery in heart
failure patients. Results are expected to be published in 2009 and 2011.[44]

The Batista procedure was invented by Brazilian doctor Randas Batista in 1994 for use in
patients with non-ischemic dilated cardiomyopathy. It involves removal of a portion of
viable tissue from the left ventricle to reduce its size (partial left ventriculectomy), with
or without repair or replacement of the mitral valve.[45]. Although several studies showed
benefits from this surgery, studies at the Cleveland Clinic concluded that this procedure
was associated with a high early and late failure rate. At 3 years only 26 percent were
event-free and survival rate was only 60 percent.[46] Most hospitals have abandoned this
operation and it is no longer included in heart failure guidelines.[38]
Newer procedures under examination are based on the observation that the spherical
configuration of the dilated heart reduces ejection fraction compared to the elliptical
form. Mesh-like constraint devices such as the Acorn CorCap aim to improve contraction
efficacy and prevent further remodeling. Clinical trials are underway.[47] Another
technique which aims to divide the spherical ventricle into two elliptical halves is used
with the Myosplint device.[48]

Approach
Acute decompensation
In acute decompensated heart failure, the immediate goal is to re-establish adequate
perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing,
and circulation are secure. Supplemental oxygen should be administered immediately to
correct hypoxemia. Acute decompensation may be complicated by respiratory failure,
which will require treatment with endotracheal intubation and mechanical ventilation.
While heart failure is associated with a volume overloaded state, volume status should be
adequately evaluated. Since heart failure patients are generally on chronic diuretics,
overdiuresis can occur. In the case of diastolic dysfunction without systolic dysfunction,
fluid resuscitation may in fact improve circulation by decreasing heart rate, which will
allow the ventricles more time to fill. Even if the patient is edematous, fluid resuscitation
may be the first line of treatment if the patient is hypotensive. The patient may in fact be
intravascularly volume depleted, although if the hypotension is due to cardiogenic shock,
additional fluid may make the situation worse. If the patient's circulatory volume is
adequate but there is persistent evidence of inadequate end-organ perfusion, inotropes
may be administered. In certain circumstances, a left-ventricle assist device (LVAD) may
be necessary.
Certain scenarios will require emergent consultation with cardiothoracic surgery. Heart
failure due to acute aortic regurgitation is a surgical emergency associated with high
mortality. Heart failure may occur after rupture of ventricular aneurysm. These can form
after myocardial infarction. If it ruptures on the free wall, it will cause cardiac
tamponade. If it ruptures on the intraventricular septum, it can create a ventricular septal
defect. Other causes of cardiac tamponade may also require surgical intervention,
although emergent treatment at bedside may be adequate. It should also be determined
whether the patient had a history of a repaired congenital heart disease as they often have

complex cardiac anatomy with artificial grafts and shunts that may sustain damage,
leading to acute decompensated heart failure.
Acute myocardial infarction can precipitate acute decompensated heart failure and will
necessitate emergent revascularization with thrombolytics, percutaneous coronary
intervention, or coronary artery bypass graft.
Once the patient is stabilized, attention can be turned to treating pulmonary edema to
improve oxygenation. Intravenous furosemide is generally the first line. However,
patients on long-standing diuretic regimens can become tolerant, and dosages must be
progressively increased. If high doses of furosemide are inadequate, boluses or
continuous infusions of bumetanide may be preferred. These loop diuretics may be
combined with thiazide diuretics such as oral metolazone or intravenous chlorthiazide for
a synergistic effect. Intravenous preparations are preferred because of more predictable
absorption. When a patient is extremely fluid overloaded, they can develop intestinal
edema as well, which can affect enteral absorption of medications.
Another option is nesiritide, although it should only be considered if conventional
therapy has been ineffective and the patient is extremely symptomatic.
Provided that the patient has an adequate blood pressure and is not bradycardia, a 1
selective beta-blocker such as metoprolol should be started. In cases of more severe
cardiomyopathy, a beta blocker with alpha antagonist effects such as carvedilol or
labetalol may be preferred. An ACE inhibitor or angiotensin receptor blockers should be
started as well. If the ejection fraction is poor, an aldosterone receptor antagonist should
be started as well.
The criteria for successful treatment of acute decompensated heart failure is the reestablishment of adequate oxygenation off of supplemental oxygen, adequate perfusion of
end-organs, and return to baseline symptomatology. A parameter frequently used is return
to "dry" weight. As the test is becoming more easily available, return to baseline BNP can
also serve as a measure of adequate treatment.
Chronic management
The goal is to prevent the development of acute decompensated heart failure, to
counteract the deleterious effects of cardiac remodeling, and to minimize the symptoms
that the patient suffers. In addition to pharmacologic agents (oral loop diuretics, betablockers, ACE inhibitors or angiotensin receptor blockers, vasodilators, and in severe
cardiomyopathy aldosterone receptor antagonists), behavioral modification should be
pursued, specifically with regards to dietary guidelines regarding salt and fluid intake.
Exercise should be encouraged as tolerated, as sufficient conditioning can significantly
improve quality-of-life.

In patients with severe cardiomyopathy, implantation of an automatic implantable

cardioverter defibrillator(AICD) should be considered. A select population will also
probably benefit from ventricular resynchronization.
In select cases, cardiac transplantation can be considered. While this may resolve the
problems associated with heart failure, the patient generally must remain on an
immunosuppressive regimen to prevent rejection, which has its own significant
downsides.
Palliative care and hospice
Without transplantation, heart failure caused by ischemic heart disease is not reversible,
and cardiac function typically deteriorates with time. (In particular, diastolic function
worsens as a function of age even in individuals without ischemic heart disease.) The
growing number of patients with Stage D heart failure (intractable symptoms of fatigue,
shortness of breath or chest pain at rest despite optimal medical therapy) should be
considered for palliative care or hospice, according to American College of
Cardiology/American Heart Association guidelines.

Prognosis
Prognosis in heart failure can be assessed in multiple ways including clinical prediction
rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of
clinical factors such as lab tests and blood pressure to estimate prognosis. Among several
clinical prediction rules for prognosing acute heart failure, the 'EFFECT rule' slightly
outperformed other rules in stratifying patients and identifying those at low risk of death
during hospitalization or within 30 days.[49] Easy methods for identifying low risk patients
are:

ADHERE Tree rule indicates that patients with blood urea nitrogen < 43 mg/dl
and systolic blood pressure at least 115 mm Hg have less than 10% chance of
inpatient death or complications.
BWH rule indicates that patients with systolic blood pressure over 90 mm Hg,
respiratory rate of 30 or less breaths per minute, serum sodium over 135 mmol/L,
no new ST-T wave changes have less than 10% chance of inpatient death or
complications.

A very important method for assessing prognosis in advanced heart failure patients is
cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to
heart transplantation as an indicator of prognosis. Cardiopulmonary exercise testing
involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak
oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a
VO2 max less than 12-14 cc/kg/min indicates a poorer survival and suggests that the
patient may be a candidate for a heart transplant. Patients with a VO2 max<10 cc/kg/min
have clearly poorer prognosis. The most recent International Society for Heart and Lung
Transplantation (ISHLT) guidelines

(http://www.jhltonline.org/article/PIIS1053249806004608/fulltext#sec1) also suggest two

other parameters that can be used for evaluation of prognosis in advanced heart failure,
the heart failure survival score and the use of a criteria of VE/VCO2 slope>35 from the
CPX test. The heart failure survival score is a score calculated using a combination of
clinical predictors and the VO2 max from the cardiopulmonary exercise test.

Hypertensive heart disease

Main article: Hypertensive heart disease
Hypertensive heart disease is heart disease caused by high blood pressure, especially
localised high blood pressure. Conditions that can be caused by hypertensive heart
disease include:

Left ventricular hypertrophy

Coronary heart disease
(Congestive) heart failure
Hypertensive cardiomyopathy
Cardiac arrhythmias

Inflammatory heart disease

Inflammatory heart disease involves inflammation of the heart muscle and/or the tissue
surrounding it.

Endocarditis - inflammation of the inner layer of the heart, the endocardium. The
most common structures involved are the heart valves.
Inflammatory cardiomegaly
Myocarditis - inflammation of the myocardium, the muscular part of the heart.

Valvular heart disease

Main article: Valvular heart disease
Valvular heart disease is any disease process involving one or more valves of the heart.
The valves in the right side of the heart are the tricuspid valve and the pulmonic valve.
The valves in the left side of the heart are the mitral valve and the aortic valve.

Aortic valve stenosis

Mitral valve prolapse
Valvular cardiomyopathy

Lung
From Wikipedia, the free encyclopedia
(Redirected from Lungs)
Jump to: navigation, search
For the village in Tibet, see Lung, Tibet.

The lungs flank the heart and great vessels in the chest cavity.[1]

Air enters and leaves the lungs via a conduit of cartilaginous passageways the bronchi
and bronchioles. In this image, lung tissue has been dissected away to reveal the
bronchioles[1]
The lung is the essential respiration organ in air-breathing animals, including most
tetrapods, a few fish and a few snails. The most primitive animals with a lung are the
lungfish (vertebrate) and the pulmonate snails (invertebrate). In mammals and the more
complex life forms, the two lungs are located in the chest on either side of the heart. Their
principal function is to transport oxygen from the atmosphere into the bloodstream, and
to release carbon dioxide from the bloodstream into the atmosphere. This exchange of
gases is accomplished in the mosaic of specialized cells that form millions of tiny,
exceptionally thin-walled air sacs called alveoli.

Medical terms related to the lung often begin with pulmo-, from the Latin pulmonarius
("of the lungs"), or with pneumo- (from Greek "breath")

Contents
[hide]

1 Respiratory function
2 Non respiratory functions
3 Mammalian lungs
o 3.1 Anatomy
4 Avian lungs
5 Reptilian lungs
6 Amphibian lungs
7 Invertebrate lungs
8 Origins
9 See also
10 Further reading
11 References

12 Footnotes

Respiratory function
The lungs are very important. Energy production to aerobic respiration requires oxygen
and glucose and produces carbon dioxide as a gaseous waste product, creating a need for
an efficient means of oxygen delivery to cells and excretion of carbon dioxide from cells.
In small organisms, such as single-celled bacteria, this process of gas exchange can take
place entirely by simple diffusion. In larger organisms, this is not possible; only a small
proportion of cells are close enough to the surface for oxygen from the atmosphere to
enter them through diffusion. Two major adaptations made it possible for organisms to
attain great multicellularity: an efficient circulatory system that conveyed gases to and
from the deepest tissues in the body, and a large, internalized respiratory system that
centralized the task of obtaining oxygen from the atmosphere and bringing it into the
body, whence it could rapidly be distributed to all the circulatory system. The lungs also
protect the heart from damage to a certain dergree.
In air-breathing vertebrates, respiration occurs in a series of steps. Air is brought into the
animal via the airways in reptiles, birds and mammals this often consists of the nose;
the pharynx; the larynx; the trachea (also called the windpipe); the bronchi and
bronchioles; and the terminal branches of the respiratory tree. The lungs of mammals are
a rich lattice of alveoli, which provide an enormous surface area for gas exchange. A
network of fine capillaries allows transport of blood over the surface of alveoli. Oxygen
from the air inside the alveoli diffuses into the bloodstream, and carbon dioxide diffuses
from the blood to the alveoli, both across thin alveolar membranes.

The drawing and expulsion of air is driven by muscular action; in early tetrapods, air was
driven into the lungs by the pharyngeal muscles, whereas in reptiles, birds and mammals
a more complicated musculoskeletal system is used. In the mammal, a large muscle, the
diaphragm (in addition to the internal intercostal muscles) drives ventilation by
periodically altering the intra-thoracic volume and pressure; by increasing volume and
thus decreasing pressure, air flows into the airways down a pressure gradient, and by
reducing volume and increasing pressure, the reverse occurs. During normal breathing,
expiration is passive and no muscles are contracted (the diaphragm relaxes).
Another name for this inspiration and expulsion of air is ventilation. Vital capacity is the
maximum volume of air that a person can exhale after maximum inhalation. A person's
vital capacity can be measured by a spirometer (spirometry). In combination with other
physiological measurements, the vital capacity can help make a diagnosis of underlying
lung disease.

Non respiratory functions

In addition, the lungs also:

influence the concentration of biologic substances and drugs used in medicine in

arterial blood
conversion of angiotensin I to angiotensin II by the action of diotensin-converting
enzyme
filter out small blood clots formed in veins
moving pH of blood by the bicarbonate buffering system and the partial pressure
of carbon dioxide
serve as a layer of soft, shock-absorbent protection for the heart, which the lungs
flank and nearly enclose.
filter out gas micro-bubbles occurring in the venous blood stream such as those
created after SCUBA diving (decompression).[2]

Mammalian lungs
Further information: Human lung
The lungs of mammals have a spongy texture and are honeycombed with epithelium
having a much larger surface area in total than the outer surface area of the lung itself.
The lungs of humans are typical of this type of lung.
Breathing is largely driven by the muscular diaphragm at the bottom of the thorax.
Contraction of the diaphragm pulls the bottom of the cavity in which the lung is enclosed
downward. Air enters through the oral and nasal cavities; it flows through the larynx and
into the trachea, which branches out into recoiling during normal breathing. During
exercise, the diaphragm contracts, forcing the air out more quickly and forcefully. The rib
cage itself is also able to expand and contract to some degree, through the action of other

respiratory and accessory respiratory muscles. As a result, air is sucked into or expelled
out of the lungs, always moving down its pressure gradient. This type of lung is known as
a bellows lung as it resembles a blacksmith's bellows.[3]

Anatomy
In humans, the trachea divides into the two main bronchi that enter the roots of the lungs.
The bronchi continue to divide within the lung, and after multiple divisions, give rise to
bronchioles. The bronchial tree continues branching until it reaches the level of terminal
bronchioles, which lead to alveolar sacks. Alveolar sacs are made up of clusters of
alveoli, like individual grapes within a bunch. The individual alveoli are tightly wrapped
in blood vessels, and it is here that gas exchange actually occurs. Deoxygenated blood
from the heart is pumped through the pulmonary artery to the lungs, where oxygen
diffuses into blood and is exchanged for carbon dioxide in the hemoglobin of the
erythrocytes. The oxygen-rich blood returns to the heart via the pulmonary veins to be
pumped back into systemic circulation.

1:Trachea 2:Pulmonary artery 3:Pulmonary vein 4:Alveolar duct 5:Alveoli 6:Cardiac

notch 7:Bronchioles 8:Tertiary bronchi 9:Secondary bronchi 10:Primary bronchi
11:Larynx
Human lungs are located in two cavities on either side of the heart. Though similar in
appearance, the two are not identical. Both are separated into lobes, with three lobes on
the right and two on the left. The lobes are further divided into lobules, hexagonal
divisions of the lungs that are the smallest subdivision visible to the naked eye. The
connective tissue that divides lobules is often blackened in smokers and city dwellers.
The medial border of the right lung is nearly vertical, while the left lung contains a
cardiac notch. The cardiac notch is a concave impression molded to accommodate the
shape of the heart. Lungs are to a certain extent 'overbuilt' and have a tremendous reserve
volume as compared to the oxygen exchange requirements when at rest. This is the
reason that individuals can smoke for years without having a noticeable decrease in lung
function while still or moving slowly; in situations like these only a small portion of the
lungs are actually perfused with blood for gas exchange. As oxygen requirements

increase due to exercise, a greater volume of the lungs is perfused, allowing the body to
match its CO2/O2 exchange requirements.
The environment of the lung is very moist, which makes it hospitable for bacteria. Many
respiratory illnesses are the result of bacterial or viral infection of the lungs.

Avian lungs
Avian lungs do not have alveoli, as mammalian lungs do, but instead contain millions of
tiny passages known as para-bronchi, connected at both ends by the dorsobronchi and
that the airflow through the avian lung always travels in the same direction - posterior to
anterior. This is in contrast to the mammalian system, in which the direction of airflow in
the lung is tidal, reversing between inhalation and exhalation. By utilizing a
unidirectional flow of air, avian lungs are able to extract a greater concentration of
oxygen from inhaled air. Birds are thus equipped to fly at altitudes at which mammals
would succumb to hypoxia, and this also allows them to sustain a higher metabolic rate
than an equivalent weight mammal. Because of the complexity of the system,
misunderstanding is common and it is incorrectly believed that that it takes two breathing
cycles for air to pass entirely through a bird's respiratory system. A bird's lungs do not
store air in either of the sacs between respiration cycles, air moves continuously from the
posterior to anterior air sacs throughout respiration. This type of lung construction is
called circulatory lungs as distinct from the bellows lung possessed by most other
animals.

Reptilian lungs
Reptilian lungs are typically ventilated by a combination of expansion and contraction of
the ribs via axial muscles and buccal pumping. Crocodilians also rely on the hepatic
piston method, in which the liver is pulled back by a muscle anchored to the pubic bone
(part of the pelvis), which in turn pulls the bottom of the lungs backward, expanding
them.

Amphibian lungs
The lungs of most frogs and other amphibians are simple balloon-like structures, with gas
exchange limited to the outer surface area of the lung. This is not a very efficient
arrangement, but amphibians have low metabolic demands and also frequently
supplement their oxygen supply by diffusion across the moist outer skin of their bodies.
Unlike mammals, which use a breathing system driven by negative pressure, amphibians
employ positive pressure. The majority of salamander species are lungless salamanders
which conduct respiration through their skin and the tissues lining their mouth. The only
other known lungless tetrapods are also amphibians the Bornean Flat-headed Frog
(Barbourula kalimantanensis) and Atretochoana eiselti, a caecilian.

Invertebrate lungs
Some invertebrates have "lungs" that serve a similar respiratory purpose, but are not
evolutionarily related to, vertebrate lungs. Some arachnids have structures called "book
lungs" used for atmospheric gas exchange. The Coconut crab uses structures called
branchiostegal lungs to breathe air and indeed will drown in water, hence it breathes on
land and holds its breath underwater. The Pulmonata are an order of snails and slugs that
have developed "lungs".

Origins
The lungs of today's terrestrial vertebrates and the gas bladders of today's fish have
evolved from simple sacs (outpocketings) of the esophagus that allowed the organism to
gulp air under oxygen-poor conditions. Thus the lungs of vertebrates are homologous to
the gas bladders of fish (but not to their gills). This is reflected by the fact that the lungs
of a fetus also develop from an outpocketing of the esophagus and in the case of gas
bladders, this connection to the gut continues to exist as the pneumatic duct in more
"primitive" teleosts, and is lost in the higher orders. (This is an instance of correlation
between ontogeny and phylogeny.) There are currently no known animals which have
both a gas bladder and lungs.

Respiratory disease
From Wikipedia, the free encyclopedia
(Redirected from Lung diseases)
Jump to: navigation, search
Respiratory Disease is the term for diseases of the respiratory system. These include
diseases of the lung, pleural cavity, bronchial tubes, trachea, upper respiratory tract and
of the nerves and muscles of breathing. Respiratory disease ranges from mild and selflimiting such as the common cold to life-threatening such as bacterial pneumonia or
pulmonary embolism. They are a common and important cause of illness and death. In
the US, Adults average between 2 and 4 colds a year, children between 6 and 10[1]. One in
seven people in the UK is affected by some form of chronic lung disease, most
commonly chronic obstructive pulmonary disease and asthma [2]. Respiratory disease is
responsible for over 10% of hospitalizations and over 16% of deaths in Canada[3]. The
study of respiratory disease is known as pulmonology. A doctor who specializes in
respiratory disease is known as a pulmonologist, a chest medicine specialist, a respiratory
medicine specialist, a respirologist or a thoracic medicine specialist.

Contents
[hide]

1 Symptoms
2 Diagnostic tests
3 Treatment
4 Respiratory diseases
o 4.1 Obstructive lung diseases
4.1.1 Chronic obstructive pulmonary disease[4]
4.1.2 Asthma
4.1.3 Other obstructive lung diseases
o 4.2 Restrictive lung diseases[8]
o 4.3 Respiratory tract infections
4.3.1 Upper respiratory tract infection
4.3.2 Lower respiratory tract infection
o 4.4 Respiratory tumours
4.4.1 Malignant tumours
4.4.2 Benign tumours
o 4.5 Pleural cavity diseases
o 4.6 Pulmonary vascular diseases
o 4.7 Disorders of breathing mechanics

5 References

Symptoms
The symptoms of respiratory disease differ depending on the disease. Common
symptoms are:

Shortness of breath or dyspnea which usually occurs with exercise and can
interfere with daily activities. In severe cases, shortness of breath occurs while
resting.
Cough with or without the production of sputum.
Coughing blood (haemoptysis).
Chest pain. This may or may not be pleuritic chest pain (that is pain that worsens
with the movements of breathing).
Noisy breathing, either wheeze or stridor.
Somnolence.
Loss of appetite.
Weight loss.
Cyanosis, a bluish discoloration of the lips, tongue or fingers.

In some cases respiratory disease is diagnosed without symptoms in the investigation of

another disease or through a routine check.

Diagnostic tests

Respiratory diseases may be investigated by perfoming one or more of the following tests

Chest x-ray
Pulmonary function test
Computed tomography scan
Culture of microorganisms from secretions such as sputum
Bronchoscopy
Biopsy of the lung or pleura
Ventilation - perfusion scan

Treatment
Treatment of respiratory disease depends on the particular disease being treated, the
severity of disease and the patient. Lifestyle factors such as regular exercise and healthy
nutrition are important in preventing and treating respiratory disease. Vaccination can
prevent some respiratory diseases. In addition, the following treatments are often used for
respiratory diseases:

Medication, often given in an inhaled form

o Corticosteroids
o Bronchodilators
o Antibiotics
o Anticoagulants
o Cancer chemotherapy
o Immune suppressants
Physiotherapy
Oxygen
Mechanical ventilation
Radiotherapy
Surgery
o Removal of a cancer e.g. lobectomy, pneumonectomy
o Pleurodesis
o Lung volume reduction surgery
o Lung transplantation

Respiratory diseases
Respiratory diseases can be classified in many different ways; by the organ involved, by
the pattern of symptoms or by the cause of the disease.

Obstructive lung diseases

These are diseases of the lung where the bronchial tubes become narrowed making it hard
to move air in and especially out of the lung.

Chronic obstructive pulmonary disease[4]

Main article: Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive
airways disease (COAD) or chronic airflow limitation (CAL), is a group of illnesses
characterised by airflow limitation that is not fully reversible. The flow of air into and out
of the lungs is impaired. This can be measured with breathing devices such as a peak flow
meter or by spirometry. The term COPD includes the conditions emphysema and chronic
bronchitis although most patients with COPD have characteristics of both conditions to
varying degrees. Asthma being a reversible obstruction of airways is often considered
separately, but many COPD patients also have some degree of reversibility in their
airways.
In COPD, there is an increase in airway resistance, shown by a decrease in the forced
expiratory volume in 1 second (FEV1) measured by spirometry. COPD is defined as a
forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) that is
less than 0.7[5]. The residual volume, the volume of air left in the lungs following full
expiration, is often increased in COPD, as is the total lung capacity, while the vital
capacity remains relatively normal. The increased total lung capacity (hyperinflation) can
result in the clinical feature of a "barrel chest" - a chest with a large front-to-back
diameter that occurs in some individuals with COPD. Hyperinflation can also be seen on
a chest x-ray as a flattening of the diaphragm.
The most common cause of COPD is cigarette smoking. COPD is a gradually progressive
condition and usually only develops after about 20 pack-years of smoking. COPD may
also be caused by breathing in other particles and gasses.
The disagnosis of COPD is established through spirometry although other pulmonary
function tests can be helpful. A chest x-ray is often ordered to look for hyperinflation and
rule out other lung conditions but the lung damage of COPD is not always visible on a
chest x-ray. Emphysema, for example can only be seen on CT scan.
The main form of long term management involves the use of inhaled bronchodilators
(specifically beta agonists and anticholinergics) and inhaled corticosteroids. Many
patients eventually require oxygen supplementation at home. In severe cases that are
difficult to control, chronic treatment with oral corticosteroids may be necessary,
although this is fraught with significant side-effects.
COPD is generally irreversible although lung function can partially recover if the patient
stops smoking. Smoking cessation is an essential aspect of treatment[6]. Pulmonary
rehabilitation programmes involve intensive exercise training combined with education
and are effective in improving shortness of breath. Severe emphysema has been treated
with lung volume reduction surgery with some success in carefully chosen cases. Lung
transplantation is also performed for severe COPD in carefully chosen cases.

Alpha 1-antitrypsin deficiency is a fairly rare genetic condition that results in COPD
(particularly emphysema) due to a lack of the antitrypsin protein which protects the
fragile alveolar walls from protease enzymes released by inflammatory processes.
Asthma
Main article: Asthma
Asthma is an obstructive lung disease where the bronchial tubes (airways) are extra
sensitive (hyperresponsive). The airways become inflamed and produce excess mucus
and the muscles around the airways tighten making the airways narrower. Asthma is
usually triggered by breathing in things in the air such as dust or pollen that produce an
allergic reaction. It may be triggered by other things such as an upper respiratory tract
infection, cold air, exercise or smoke. Asthma is a common condition and affects over
300 million people around the world[7]. Asthma causes recurring episodes of wheezing,
breathlessness, chest tightness, and coughing, particularly at night or in the early
morning.
Asthma is diagnosed by the characteristic pattern of symptoms. A peak flow meter can
record variations in the severity of asthma over time. Spirometry, a measurement of lung
function, can provide an assessment of the severity, reversibility, and variability of
airflow limitation, and help confirm the diagnosis of asthma[7].
Asthma is treated by identifying and removing the triggers that set it off, if possible. The
main form of long term management involves the use of inhaled corticosteroids. Inhaled
bronchodilators, particularly beta agonists are used to relieve and control symptoms by
reducing muscle spasm around the airways. An alternative way to control mild asthma is
with a leukotriene antagonist tablet.
Other obstructive lung diseases

Cystic fibrosis is an inherited disorder of the CFTR gene, a chloride ion channel.
The lack of this channel causes reduced water content of secretions. This affects
the mucus secreted as part of the lung's defence and creates sticky, viscous mucus.
This makes the lungs more susceptible to infection, inflammation and mucous
plugging.
Bronchiectasis
Bronchiolitis
Allergic bronchopulmonary aspergillosis

In many parts of the world, the most common cause of obstructive lung disease is lung
scarring after tuberculosis infection.

Restrictive lung diseases[8]

Restrictive lung diseases (also known as interstitial lung diseases) are characterised by a
loss of lung compliance, causing incomplete lung expansion and increased lung stiffness.
The underlying process is usually pulmonary fibrosis (scarring of the lung). As the
disease progresses, the normal lung tissue is gradually replaced by scar tissue
interspersed with pockets of air. This can lead to parts of the lung having a honeycomblike appearance.
The main symptoms are shortness of breath and cough.
In restrictive lung disease, both the FEV1 and FVC are reduced so the FEV1/FVC ratio is
normal or even increased in contrast to obstructive lung disease where this ratio is
reduced. The values for residual volume and total lung capacity are generally decreased
in restrictive lung disease[9].
Restrictive lung diseases may be due to a specific cause such as:

Asbestosis caused by long-term exposure to asbestos dust.

Radiation fibrosis, usually from the radiation given for cancer treatment.
Certain drugs such as amiodarone, bleomycin and methotrexate.
As a consequence of another disease such as rheumatoid arthritis.
Hypersensitivity pneumonitis due to an allergic reaction to inhaled particles.
Acute respiratory distress syndrome (ARDS), a severe lung condition occuring in
response to a critical illness or injury.
Infant respiratory distress syndrome due to a deficiency of surfactant in the lungs
of a baby born prematurely.

Many cases of restrictive lung disease are idiopathic (have no known cause). Examples
are:

Idiopathic pulmonary fibrosis

Idiopathic interstial pneumonia, of which there are several types
Sarcoidosis
Eosinophilic pneumonia
Lymphangioleiomyomatosis
Pulmonary Langerhans cell histiocytosis
Pulmonary alveolar proteinosis

Respiratory tract infections

Infections can affect any part of the respiratory system. They are traditionally divided
into upper respiratory tract infections and lower respiratory tract infections.
Upper respiratory tract infection
The most common upper respiratory tract infection is the common cold however
infections of specific organs of the upper respiratory tract such as sinusitis, tonsillitis,

otitis media, pharyngitis and laryngitis are also considered upper respiratory tract
infections.
Lower respiratory tract infection
The most common lower respiratory tract infection in is pneumonia, a lung infection.
Pneumonia is usually caused by bacteria, particularly [[Streptococcus pneumoniae]] in
Western countries. Worldwide, tuberculosis is an important cause of pneumonia. Other
pathogens such as viruses and fungi can cause pneumonia for example severe acute
respiratory syndrome and pneumocystis pneumonia. A pneumonia may develop
complications such as a lung abscess, a round cavity in the lung caused by the infection
or an empyema, the spread of the infection to the pleural cavity.

Respiratory tumours
Tumours of the respiratory system are either malignant or benign.
Malignant tumours
Malignant tumours, or cancers of the respiratory system, particularly lung cancers, are a
major health problem responsible for 15% of all cancer diagnoses and 29% of all cancer
deaths[10]. The majority of respiratory system cancers are attributable to smoking tobacco.
The major types of respiratory system cancer are:

Small cell lung cancer

Non-small cell lung cancer
o Adenocarcinoma
o Squamous cell carcinoma
o Large cell undifferentiated carcinoma
Other lung cancers (carcinoid, Kaposis sarcoma, melanoma)
Lymphoma
Head and neck cancer
Mesothelioma, usually caused by exposure to asbestos dust.

In addition, since many cancers spread via the bloodstream and the entire cardiac output
passes through the lungs, it common for cancer metastases to occur the lung. Breast
cancer may invade directly through local spread, and through lymph node metastases.
After metastasis to the liver, colon cancer frequently metastasizes to the lung. Prostate
cancer, germ cell cancer and renal cell carcinoma may also metastasize to the lung.
Treatment of respiratory system cancer depends on the type of cancer. Surgery (usually
removal of part of the lung, a lobectomy or an entire lung, a pneumonectomy),
chemotherapy and radiotherapy are all used. The chance of surviving lung cancer
depends on the cancer stage at the time the cancer is diagnosed and is only about 14-17%

overall[11]. In the case of metastases to the lung, treatment can occasionally be curative but
only in certain, rare circumstances.
Benign tumours
Benign tumours are relatively rare causes of respiratory disease. Examples of benign
tumours are:

Pulmonary hamartoma
Congenital malformations such as pulmonary sequestration and congenital cystic
adenomatoid malformation (CCAM).

Pleural cavity diseases

Pleural cavity diseases include empyema and mesothelioma which are mentioned above.
A collection of fluid in the pleural cavity is known as a pleural effusion. This may be due
to fluid shifting from the bloodstream into the pleural cavity due to conditions such as
congestive heart failure and cirrhosis. It may also be due to inflammation of the pleura
itself as can occur with infection, pulmonary embolus, tuberculosis, mesothelioma and
other conditions.
A pneumothorax is a hole in the pleura covering the lung allowing air in the lung to
escape into the pleural cavity. The affected lung collapses like a deflated baloon. A
tension pneumothorax is a particularly severe form of this condition where the air in the
pleural cavity cannot escape, so the the pneumothorax keeps getting bigger until it
compresses the heart and blood vessels, leading to a life threatening situation.

Pulmonary vascular diseases

Pulmonary vascular diseases are conditions that affect the pulmonary circulation.
Examples of these conditions are:

Pulmonary embolism, a blood clot that forms in a vein, breaks free, travels
through the heart and lodges in the lungs (thromboembolism). Large pulmonary
emboli are fatal, causing sudden death. A number of other substances can also
embolise to the lungs but they are much more rare: fat embolism (particularly
after bony injury), amniotic fluid embolism (with complications of labour and
delivery), air embolism (iatrogenic).
Pulmonary arterial hypertension, elevated pressure in the pulmonary arteries. It
can be idiopathic or due to the efects of another disease, particularly COPD. This
can lead to strain on the right side of the heart, a condition known as cor
pulmonale.
Pulmonary edema, leakage of fluid from capillaries of the lung into the alveoli (or
air spaces). It is usually due to congestive heart failure.

Pulmonary hemorrhage, inflammation and damage to capillaries in the lung

resulting in blood leaking into the alveoli. This may cause blood to be coughed
up. Pulmonary hemhorrage can be due to auto-immune disorders such as
Wegener's Granulomatosis and Goodpasture's syndrome.

Disorders of breathing mechanics

The brain co-ordinates breathing and sends messages via nerves to the muscles of
respiration. The muscles produce the movements of breathing. Disorders of the brains
control of breathing, the nerves or the muscles of respiration can affect the respiratory
system. Common disorders of breathing mechanics are:

Obstructive sleep apnea

Central sleep apnea
Amyotrophic lateral sclerosis
Guillan-Barre syndrome
Myasthenia gravis

Obesity is often associated with sleep apnea and can cause either an obstructive or a
restrictive pattern on spirometry. Obesity reduces the movement of the chest wall which
can, in extreme cases, result in the obesity-hypoventilation syndrome, a cause of
respiratory failure.

Brain
From Wikipedia, the free encyclopedia.

In animals, the brain is the control center of the central nervous system, responsible for
behavior. In mammals, the brain is located in the head, protected by the skull and close to
the primary sensory apparatus of vision, hearing, equilibrioception (balance), sense of
taste, and olfaction (smell).

While all vertebrates have a brain, most invertebrates have either a centralized brain or
collections of individual ganglia. Some animals such as cnidarians and echinoderms do
not have a centralized brain, and instead have a decentralized nervous system, while
animals such as sponges lack both a brain and nervous system entirely.
Brains can be extremely complex. For example, the human brain contains roughly
100 billion neurons, each linked to as many as 10,000 other neurons.

Contents
[hide]

1 History
2 Mind and brain
3 Comparative anatomy
o 3.1 Insects
o 3.2 Cephalopods
o 3.3 Mammals and other vertebrates
3.3.1 Vertebrate brain regions
3.3.2 Humans
4 Neurobiology
o 4.1 Structure
o 4.2 Function
4.2.1 Neurotransmitter systems
o 4.3 Origin
o 4.4 Pathology
5 Study of the brain
o 5.1 Fields of study
o 5.2 Methods of observation
5.2.1 Electrophysiology
5.2.2 EEG
5.2.3 MEG
5.2.4 fMRI and PET
5.2.5 Behavioral
5.2.6 Anatomical
o 5.3 Other studies
6 As food
7 Brain energy consumption
8 See also
9 Further reading
10 References

11 External links

History

Main article: History of the brain

Early views on the function of the brain regarded it as little more than cranial stuffing. In
Ancient Egypt, from the late Middle Kingdom onwards, in preparation for
mummification, the brain was regularly removed, for it was the heart that was assumed to
be the seat of intelligence. According to Herodotus, during the first step of
mummification, "The most perfect practice is to extract as much of the brain as possible
with an iron hook, and what the hook cannot reach is mixed with drugs." Over the next
five-thousand years, this view came to be reversed; the brain is now known to be seat of
intelligence, although idiomatic variations of the former remain, as in memorizing
something "by heart".[1]
The first thoughts on the field of psychology came from ancient philosophers, such as
Aristotle. As thinkers became more in tune with biomedical research over time, as was
the case with medieval psychologists such as Alhazen and Avicenna for example, the
concepts of experimental psychology and clinical psychology began emerging. From that
point, different branches of psychology emerged with different individuals creating new
ideas, with modern psychologists such as Freud and Jung contributing to the field.

Mind and brain

The distinction between the mind and the brain is fundamental in philosophy of mind.
The mind-body problem is one of the central problems in the history of philosophy. The
brain is the physical and biological matter contained within the skull, responsible for
electrochemical neuronal processes. The mind, in contrast, consists in mental attributes,
such as beliefs, desires, perceptions, and so on. There are scientifically demonstrable
correlations between mental events and neuronal events; the philosophical question is
whether these phenomena are identical, at least partially distinct, or related in some other
way.
Philosophical positions on the mind-body problem fall into two main categories. The first
category is dualism, according to which the mind exists independently of the brain.
Dualist theories are further divided into substance dualism and property dualism. Ren
Descartes is perhaps the most prominent substance dualist, while property dualism is
more popular among contemporary dualists like David Chalmers. The second category is
materialism, according to which mental phenomena are identical to neuronal
phenomena. A third category of view, idealism, claims that only mental substances and
phenomena exist. This view, most prominently held by 18th century Irish philosopher
Bishop George Berkeley, has few contemporary adherents.
Both dualism and materialism face serious philosophical challenges. Dualism requires
admitting non-physical substances or properties into ontology, which is in apparent
conflict with the scientific world view. Materialism, on the other hand, must provide an
explanation of how two seemingly different kinds of phenomena the mental and the
physical could be identical. This is particularly challenging in that mental phenomena
have certain characteristics particularly intentionality and phenomenal character that

cannot (at least currently) be explained satisfactorily by a purely physical analysis of the
brain.

Comparative anatomy

A mouse brain.
Three groups of animals have notably complex brains: the arthropods (insects,
crustaceans, arachnids, and others), the cephalopods (octopuses, squids, and similar
mollusks), and the craniates (vertebrates and hagfish).[2] The brain of arthropods and
cephalopods arises from twin parallel nerve cords that extend through the body of the
animal. Arthropods have a central brain with three divisions and large optical lobes
behind each eye for visual processing.[2]
The brain of craniates develops from the anterior section of a single dorsal nerve cord,
which later becomes the spinal cord.[3] In craniates, the brain is protected by the bones of
the skull.
Mammals have a six-layered neocortex (or homotypic cortex, neopallium), in addition to
having some parts of the brain that are allocortex.[3] In mammals, increasing convolutions
of the brain are characteristic of animals with more advanced brains. These convolutions
provide a larger surface area for a greater number of neurons while keeping the volume of
the brain compact enough to fit inside the skull. The folding allows more grey matter to
fit into a smaller volume. The folds are called sulci, while the spaces between the folds
are called gyri.
In birds, the part of the brain that functionally corresponds to the neocortex is called
nidopallium and derives from a different part of the brain. Some birds (like corvids and
parrots), are thought by some to have high intelligence, but even in these, the brain region
that forms the mammalian neocortex is in fact almost entirely absent.
Although the general histology of the brain is similar from person to person, the
structural anatomy can differ. Apart from the gross embryological divisions of the brain,
the location of specific gyri and sulci, primary sensory regions, and other structures
differs between species.

Insects

In insects, the brain has four parts, the optical lobes, the protocerebrum, the
deutocerebrum, and the tritocerebrum. The optical lobes are behind each eye and process
visual stimuli.[2] The protocerebrum contains the mushroom bodies, which respond to
smell, and the central body complex. In some species such as bees, the mushroom body
receives input from the visual pathway as well. The deutocerebrum includes the antennal
lobes, which are similar to the mammalian olfactory bulb, and the mechanosensory
neuropils which receive information from touch receptors on the head and antennae. The
antennal lobes of flies and moths are quite complex.

Cephalopods
In cephalopods, the brain has two regions: the supraesophageal mass and the
subesophageal mass,[2] separated by the esophagus. The supra- and subesophageal masses
are connected to each other on either side of the esophagus by the basal lobes and the
dorsal magnocellular lobes.[2] The large optic lobes are sometimes not considered to be
part of the brain, as they are anatomically separate and are joined to the brain by the optic
stalks. However, the optic lobes perform much visual processing, and so functionally are
part of the brain.

Mammals and other vertebrates

The telencephalon (cerebrum) is the largest region of the mammalian brain. This is the
structure that is most easily visible in brain specimens, and is what most people associate
with the "brain". In humans and several other animals, the fissures (sulci) and
convolutions (gyri) give the brain a wrinkled appearance. In non-mammalian vertebrates
with no cerebrum, the metencephalon is the highest center in the brain. Because humans
walk upright, there is a flexure, or bend, in the brain between the brain stem and the
cerebrum. Other vertebrates do not have this flexure. Generally, comparing the locations
of certain brain structures between humans and other vertebrates often reveals a number
of differences.
Behind (or in humans, below) the cerebrum is the cerebellum. The cerebellum is known
to be involved in the control of movement,[3] and is connected by thick white matter fibers
(cerebellar peduncles) to the pons.[4] The cerebrum has two cerebral hemispheres. The
cerebellum also has hemispheres. The telencephalic hemispheres are connected by the
corpus callosum, another large white matter tract. An outgrowth of the telencephalon
called the olfactory bulb is a major structure in many animals, but in humans and other
primates it is relatively small.
Vertebrate nervous systems are distinguished by bilaterally symmetrical encephalization.
Encephalization refers to the tendency for more complex organisms to gain larger brains
through evolutionary time. Larger vertebrates develop a complex, layered and
interconnected neuronal circuitry. In modern species most closely related to the first
vertebrates, brains are covered with gray matter that has a three-layer structure
(allocortex). Their brains also contain deep brain nuclei and fiber tracts forming the white

matter. Most regions of the human cerebral cortex have six layers of neurons (neocortex).
[4]

Vertebrate brain regions

(See related article at List of regions in the human brain)

Diagram depicting the main subdivisions of the embryonic vertebrate brain. These
regions will later differentiate into forebrain, midbrain and hindbrain structures.
According to the hierarchy based on embryonic and evolutionary development, chordate
brains are composed of the three regions that later develop into five total divisions:

Rhombencephalon (hindbrain)
o Myelencephalon
o Metencephalon
Mesencephalon (midbrain)
Prosencephalon (forebrain)
o Diencephalon
o Telencephalon

The brain can also be classified according to function, including divisions such as:

Limbic system
Sensory systems
o Visual system
o Olfactory system
o Gustatory system
o Auditory system
o Somatosensory system
Motor system
Associative areas

In recent years it was realized that certain birds have developed high intelligence entirely
convergently from mammals such as humans. Hence, the functional areas of the avian
brain have been redefined by the Avian Brain Nomenclature Consortium. See also Bird
intelligence.

Humans

Human brain with color coded lobes

Main article: Human brain
The structure of the human brain differs from that of other animals in several important
ways. These differences allow for many abilities over and above those of other animals,
such as advanced cognitive skills. Human encephalization is especially pronounced in the
neocortex, the most complex part of the cerebral cortex. The proportion of the human
brain that is devoted to the neocortexespecially to the prefrontal cortexis larger than
in all other mammals (indeed larger than in all animals, although only in mammals has
the neocortex evolved to fulfill this kind of function).
Humans have unique neural capacities, but much of their brain structure is similar to that
of other mammals. Basic systems that alert the nervous system to stimulus, that sense
events in the environment, and monitor the condition of the body are similar to those of
even non-mammalian vertebrates. The neural circuitry underlying human consciousness
includes both the advanced neocortex and prototypical structures of the brainstem. The
human brain also has a massive number of synaptic connections allowing for a great deal
of parallel processing.
The human brain is also the largest organ in the Nervous System.

Neurobiology
The brain is composed of two broad classes of cells, neurons and glia, both of which
contain several different cell types which perform different functions. Interconnected
neurons form neural networks (or neural ensembles). These networks are similar to manmade electrical circuits in that they contain circuit elements (neurons) connected by
biological wires (nerve fibers). These do not form simple one-to-one electrical circuits
like many man-made circuits, however. Typically neurons connect to at least a thousand
other neurons.[5] These highly specialized circuits make up systems which are the basis of
perception, different types of action, and higher cognitive function.

Structure
Structure of a typical neuron
Neuron

Dendrite
Soma
Axon
Nucleus
Node of
Ranvier
Axon Terminal
Schwann cell
Myelin sheath
Neurons are the cells that convey information to other cells; these constitute the essential
class of brain cells.
In addition to neurons, the brain contains glial cells in a roughly 10:1 proportion to
neurons. Glial cells ("glia" is Greek for glue) form a support system for neurons. They
create the insulating myelin, provide structure to the neuronal network, manage waste,
and clean up neurotransmitters. Most types of glia in the brain are present in the entire
nervous system. Exceptions include the oligodendrocytes which myelinate neural axons
(a role performed by Schwann cells in the peripheral nervous system). The myelin in the
oligodendrocytes insulates the axons of some neurons. White matter in the brain is
myelinated neurons, while grey matter contains mostly cell soma, dendrites, and
unmyelinated portions of axons and glia. The space between neurons is filled with
dendrites as well as unmyelinated segments of axons; this area is referred to as the
neuropil.
In mammals, the brain is surrounded by connective tissues called the meninges, a system
of membranes that separate the skull from the brain. This three-layered covering is
composed of (from the outside in) the dura mater, arachnoid mater, and pia mater. The
arachnoid and pia are physically connected and thus often considered as a single layer,
the pia-arachnoid. Below the arachnoid is the subarachnoid space which contains

cerebrospinal fluid, a substance that protects the nervous system. Blood vessels enter the
central nervous system through the perivascular space above the pia mater. The cells in
the blood vessel walls are joined tightly, forming the blood-brain barrier which protects
the brain from toxins that might enter through the blood.
The brain is bathed in cerebrospinal fluid (CSF), which circulates between layers of the
meninges and through cavities in the brain called ventricles. It is important both
chemically for metabolism and mechanically for shock-prevention. For example, the
human brain weighs about 1-1.5 kg or about 2-3 lb. The mass and density of the brain are
such that it will begin to collapse under its own weight if unsupported by the CSF. The
CSF allows the brain to float, easing the physical stress caused by the brains mass.

Function
Vertebrate brains receive signals through nerves arriving from the sensors of the
organism. These signals are then processed throughout the central nervous system;
reactions are formulated based upon reflex and learned experiences. A similarly extensive
nerve network delivers signals from a brain to control important muscles throughout the
body. Anatomically, the majority of afferent and efferent nerves (with the exception of the
cranial nerves) are connected to the spinal cord, which then transfers the signals to and
from the brain.
Sensory input is processed by the brain to recognize danger, find food, identify potential
mates, and perform more sophisticated functions. Visual, touch, and auditory sensory
pathways of vertebrates are routed to specific nuclei of the thalamus and then to regions
of the cerebral cortex that are specific to each sensory system, the visual system, the
auditory system, and the somatosensory system. Olfactory pathways are routed to the
olfactory bulb, then to various parts of the olfactory system. Taste is routed through the
brainstem and then to other portions of the gustatory system.
To control movement the brain has several parallel systems of muscle control. The motor
system controls voluntary muscle movement, aided by the motor cortex, cerebellum, and
the basal ganglia. The system eventually projects to the spinal cord and then out to the
muscle effectors. Nuclei in the brain stem control many involuntary muscle functions
such as heart rate and breathing. In addition, many automatic acts (simple reflexes,
locomotion) can be controlled by the spinal cord alone.
Brains also produce a portion of the body's hormones that can influence organs and
glands elsewhere in a bodyconversely, brains also react to hormones produced
elsewhere in the body. In mammals, the hormones that regulate hormone production
throughout the body are produced in the brain by the structure called the pituitary gland.
Evidence strongly suggests that developed brains derive consciousness from the complex
interactions between the numerous systems within the brain. Cognitive processing in
mammals occurs in the cerebral cortex but relies on midbrain and limbic functions as

well. Among "younger" (in an evolutionary sense) vertebrates, advanced processing

involves progressively rostral (forward) regions of the brain.
Hormones, incoming sensory information, and cognitive processing performed by the
brain determine the brain state. Stimulus from any source can trigger a general arousal
process that focuses cortical operations to processing of the new information. This
focusing of cognition is known as attention. Cognitive priorities are constantly shifted by
a variety of factors such as hunger, fatigue, belief, unfamiliar information, or threat. The
simplest dichotomy related to the processing of threats is the fight-or-flight response
mediated by the amygdala and other limbic structures.
Neurotransmitter systems
Main article: Neurotransmitter systems
Neurons expressing certain types of neurotransmitters sometimes form distinct systems,
where activation of the system causes effects in large volumes of the brain, called volume
transmission.
The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the
dopamine system, the serotonin system and the cholinergic system.
Drugs targeting the neurotransmitter of such systems affects the whole system, which
explains the mode of action of many drugs;

Cocaine, for example, blocks the reuptake of dopamine, leaving these

neurotransmitters in the synaptic gap longer.
Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the
effect of naturally released serotonin.
AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to
dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl
inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

Diseases may affect specific neurotransmitter systems. For example, Parkinson's disease
is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example
the substantia nigra. Treatments potentiating the effect of dopamine precursors have been
proposed and effected, with moderate success.
A brief comparison of the major neurotransmitter systems follows:

System

Neurotransmitter systems
[6]
Origin
Effects[6]
locus coeruleus
arousal

Noradrenaline
system
Lateral tegmental field
Dopamine

dopamine pathways:

reward
motor system, reward, cognition,

system

mesocortical pathway
mesolimbic pathway
nigrostriatal pathway

endocrine, nausea

tuberoinfundibular
pathway
caudal dorsal raphe nucleus

Serotonin system

Cholinergic
system

Increase introversion, mood, satiety,

body temperature and sleep, while
rostral dorsal raphe nucleus
decreasing nociception.
pontomesencephalotegmental
learning
complex
short-term memory
arousal
basal optic nucleus of Meynert
medial septal nucleus

reward

Origin
Since even unicellular organisms can have, at least, photosensitive eyespots and react to
tactile stimuli, it is hypothesized that sensory organs developed before the brain did.[7]
The brain is an information-processing organ and its evolution is dependent on the
presence of information accessed into sensory organs, sensory input, and the need to
process this information and transmit it.

Pathology

A human brain showing frontotemporal lobar degeneration causing frontotemporal

dementia.
Clinically, death is defined as an absence of brain activity as measured by EEG. Injuries
to the brain tend to affect large areas of the organ, sometimes causing major deficits in
intelligence, memory, and movement. Head trauma caused, for example, by vehicle or
industrial accidents, is a leading cause of death in youth and middle age. In many cases,
more damage is caused by resultant edema than by the impact itself. Stroke, caused by
the blockage or rupturing of blood vessels in the brain, is another major cause of death
from brain damage.

Other problems in the brain can be more accurately classified as diseases rather than
injuries. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease,
motor neurone disease, and Huntington's disease are caused by the gradual death of
individual neurons, leading to decrements in movement control, memory, and cognition.
Currently only the symptoms of these diseases can be treated. Mental illnesses, such as
clinical depression, schizophrenia, bipolar disorder, and post-traumatic stress disorder are
brain disorders that impact personality and, typically, other aspects of mental and somatic
function. These disorders may be treated by psychiatric therapy, pharmaceutical
intervention, or through a combination of treatments; therapeutic effectiveness varies
significantly among individuals.
Some infectious diseases affecting the brain are caused by viruses and bacteria. Infection
of the meninges, the membrane that covers the brain, can lead to meningitis. Bovine
spongiform encephalopathy (also known as mad cow disease), is deadly in cattle and
humans and is linked to prions. Kuru is a similar prion-borne degenerative brain disease
affecting humans. Both are linked to the ingestion of neural tissue, and may explain the
tendency in some species to avoid cannibalism. Viral or bacterial causes have been
reported in multiple sclerosis and Parkinson's disease, and are established causes of
encephalopathy, and encephalomyelitis.
Many brain disorders are congenital. Tay-Sachs disease, Fragile X syndrome, and Down
syndrome are all linked to genetic and chromosomal errors. Many other syndromes, such
as the intrinsic circadian rhythm disorders, are suspected to be congenital as well.
Malfunctions in the embryonic development of the brain can be caused by genetic
factors, drug use, nutritional deficiencies, and infectious diseases during pregnancy.
Certain brain disorders are treated by brain neurosurgeons while others are treated by
neurologists and psychiatrists.

Study of the brain

Fields of study
Neuroscience seeks to understand the nervous system, including the brain, from a
biological and computational perspective. Psychology seeks to understand behavior and
the brain. Neurology refers to the medical applications of neuroscience. The brain is also
one of the most important organs studied in psychiatry, the branch of medicine which
exists to study, prevent, and treat mental disorders.[8][9][10] Cognitive science seeks to unify
neuroscience and psychology with other fields that concern themselves with the brain,
such as computer science (artificial intelligence and similar fields) and philosophy.

Methods of observation
Main article: neuroimaging
Each method for observing activity in the brain has its advantages and drawbacks.

Electrophysiology
Electrophysiology allows scientists to record the electrical activity of individual neurons
or groups of neurons.
EEG
By placing electrodes on the scalp one can record the summed electrical activity of the
cortex in a technique known as electroencephalography (EEG). EEG measures the mass
changes in electrical current from the cerebral cortex, but can only detect changes over
large areas of the brain with very little sub-cortical activity.
MEG
Apart from measuring the electric field around the skull it is possible to measure the
magnetic field directly in a technique known as magnetoencephalography (MEG). This
technique has the same temporal resolution as EEG but much better spatial resolution,
although admittedly not as good as fMRI. The main advantage over fMRI is a direct
relationship between neural activation and measurement.
fMRI and PET

A scan of the brain using fMRI

Functional magnetic resonance imaging (fMRI) measures changes in blood flow in the
brain, but the activity of neurons is not directly measured, nor can it be distinguished
whether this activity is inhibitory or excitatory. fMRI is a noninvasive, indirect method
for measuring neural activity that is based on BOLD; Blood Oxygen Level Dependent
changes. The changes in blood flow that occur in capillary beds in specific regions of the
brain are thought to represent various neuronal activities (metabolism of synaptic
reuptake). Similarly, a positron emission tomography (PET), is able to monitor glucose
and oxygen metabolism as well as neurotransmitter activity in different areas within the
brain which can be correlated to the level of activity in that region.
Behavioral

Behavioral tests can measure symptoms of disease and mental performance, but can only
provide indirect measurements of brain function and may not be practical in all animals.
In humans however, a neurological exam can be done to determine the location of any
trauma, lesion, or tumor within the brain, brain stem, or spinal cord.
Anatomical
Autopsy analysis of the brain allows for the study of anatomy and protein expression
patterns, but is only possible after the human or animal is dead. Magnetic resonance
imaging (MRI) can be used to study the anatomy of a living creature and is widely used
in both research and medicine.

Other studies
Computer scientists have produced simulated "artificial neural networks" loosely based
on the structure of neuron connections in the brain. Some artificial intelligence research
seeks to replicate brain functionalthough not necessarily brain mechanismsbut as yet
has been met with limited success.
Creating algorithms to mimic a biological brain is very difficult because the brain is not a
static arrangement of circuits, but a network of vastly interconnected neurons that are
constantly changing their connectivity and sensitivity. More recent work in both
neuroscience and artificial intelligence models the brain using the mathematical tools of
chaos theory and dynamical systems. Current research has also focused on recreating the
neural structure of the brain with the aim of producing human-like cognition and artificial
intelligence.

As food

Goat brain prior to being cooked

Like most other internal organs, the brain can serve as nourishment. For example, in the
Southern United States canned pork brain in gravy can be purchased for consumption as
food. This form of brain is often fried with scrambled eggs to produce the famous "Eggs
n' Brains".[11] The brain of animals also features in French cuisine such as in the dish tte
de veau, or head of calf. Although it sometimes consists only of the outer meat of the
skull and jaw, the full meal includes the brain, tongue, and glands. Similar delicacies

from around the world include Mexican tacos de sesos made with cattle brain as well as
squirrel brain in the US South.[12] The Anyang tribe of Cameroon practiced a tradition in
which a new tribal chief would consume the brain of a hunted gorilla while another
senior member of the tribe would eat the heart.[13] Indonesian cuisine specialty in
Minangkabau cuisine also served beef brain in a gravy coconut milk named gulai otak
(beef brain curry). Roasted or fried goat brain is eaten in south India and some parts of
north India. Norwegian cuisine includes smalahove where a singed lamb's head,
including the brain, tongue and eye, serves two people.
Consuming the brain and other nerve tissue of animals is not without risks. The first
problem is that the makeup of the brain is 60% fat due to the myelin (which itself is 70%
fat) insulating the axons of neurons and glia.[14] As an example, a 140 g can of "pork
brains in milk gravy", a single serving, contains 3500 milligrams of cholesterol, 1170%
of our recommended daily intake.[15]
Brain consumption can result in contracting fatal transmissible spongiform
encephalopathies such as Variant Creutzfeldt-Jakob disease and other prion diseases in
humans and mad cow disease in cattle.[16] Another prion disease called kuru has been
traced to a funerary ritual among the Fore people of Papua New Guinea in which those
close to the dead would eat the brain of the deceased to create a sense of immortality.[17]
Some archaeological evidence suggests that the mourning rituals of European
Neanderthals also involved the consumption of the brain.[18] Because of the risk of being
infected by prions one should always wear gloves when handling brains.
It is also well-known in the hunting community that the brain of wild animals should not
be consumed, due to the risk of chronic wasting disease. The brain is still useful to
hunters, in that most animals have enough brain matter for use in the tanning of their own
hides.

Brain energy consumption

PET Image of the human brain showing energy consumption

Although the brain represents only 2% of the body weight, it receives 15% of the cardiac
output, 20% of total body oxygen consumption, and 25% of total body glucose
utilization. The energy consumption for the brain to simply survive is 0.1 calories per
minute, while this value can be as high as 1.5 calories per minute during crossword
puzzle-solving.[19] The demands of the brain limit its size in many species. Molossid bats
and the Vespertilionid Nyctalus spp. have brains that have been reduced from the
ancestral form to invest in wing-size for the sake of maneuverability. This contrasts with
fruit bats, which require more advanced neural structures and do not pursue their prey.[20]

Kidney

Human kidneys viewed from behind with spine removed

The kidneys are complicated organs that have numerous biological roles. Their primary
role is to maintain the homeostatic balance of bodily fluids by filtering and secreting
metabolites (such as urea) and minerals from the blood and excreting them, along with
water, as urine. Because the kidneys are poised to sense plasma concentrations of ions
such as sodium, potassium, hydrogen, oxygen, and compounds such as amino acids,
creatine, bicarbonate, and glucose, they are important regulators of blood pressure,
glucose metabolism, and erythropoiesis (the process by which red blood cells
(erythrocytes) are produced). The medical field that studies the kidneys and diseases of
the kidney is called nephrology[1]. The prefix nephro- meaning kidney is from the Ancient
Greek word nephros (); the adjective renal meaning related to the kidney is from
Latin rns, meaning kidneys. [2]
In humans, the kidneys are located in the posterior part of the abdomen. There is one on
each side of the spine; the right kidney sits just below the liver, the left below the
diaphragm and adjacent to the spleen. Above each kidney is an adrenal gland (also called
the suprarenal gland). The asymmetry within the abdominal cavity caused by the liver
results in the right kidney being slightly lower than the left one while the left kidney is
located slightly more medial.
The kidneys are retroperitoneal and range from 9 to 13 cm in diameter; the left slightly
larger than the right. They are approximately at the vertebral level T12 to L3. The upper
parts of the kidneys are partially protected by the eleventh and twelfth ribs, and each
whole kidney and adrenal gland are surrounded by two layers of fat (the perirenal and
pararenal fat) and the renal fascia which help to cushion it. Congenital absence of one or
both kidneys, known as unilateral or bilateral renal agenesis, can occur.

Contents
[hide]

1 Functions
o 1.1 Excretion of waste products
o 1.2 Homeostasis
1.2.1 Acid-base balance
1.2.2 Blood pressure
1.2.3 Plasma volume
o 1.3 Hormone secretion
2 Embryology
o 2.1 Pronephros
o 2.2 Mesonephros
o 2.3 Metanephros
3 Terms
4 Diseases and disorders
o 4.1 Congenital
o 4.2 Acquired
5 The failing kidney

6 Medical terminology
7 Histology
8 Animal kidneys as food
9 See also
10 References

11 External links

Functions
Main article: Renal physiology

Excretion of waste products

The kidneys excrete a variety of waste products produced by metabolism, including the
nitrogenous wastes: urea (from protein catabolism) and uric acid (from nucleic acid
metabolism) and water.

Homeostasis
The kidney is one of the major organs involved in whole-body homeostasis. Among its
homeostatic functions are acid-base balance, regulation of electrolyte concentrations,
control of blood volume, and regulation of blood pressure. The kidneys accomplish these
homeostatic functions independently and through coordination with other organs,
particularly those of the endocrine system. The kidney communicates with these organs
through hormones secreted into the bloodstream.
Acid-base balance
The kidneys regulate the pH of blood by adjusting H+ ion levels, referred as augmentation
of mineral ion concentration, as well as water composition of the blood.
Blood pressure
Main article: Renin-angiotensin system
Sodium ions are controlled in a homeostatic process involving aldosterone which
increases sodium ion reabsorption in the distal convoluted tubules.
Plasma volume
Any significant rise or drop in plasma osmolality is detected by the hypothalamus, which
communicates directly with the posterior pituitary gland. A rise in osmolality causes the
gland to secrete antidiuretic hormone, resulting in water reabsorption by the kidney and

an increase in urine concentration. The two factors work together to return the plasma
osmolality to its normal levels.

Hormone secretion
The kidneys secrete a variety of hormones, including erythropoietin, urodilatin, renin and
vitamin D.

Embryology
Main article: Development of the urinary and reproductive organs
The mammalian kidney develops from intermediate mesoderm. Kidney development,
also called nephrogenesis, proceeds through a series of three successive phases, each
marked by the development of a more advanced pair of kidneys: the pronephros,
mesonephros, and metanephros.[3] (The plural forms of these terms end in -oi.)

Pronephros
Main article: Pronephros
During approximately day 22 of human gestation, the paired pronephroi appear towards
the cranial end of the intermediate mesoderm. In this region, epithelial cells arrange
themselves in a series of tubules called nephrotomes and join laterally with the
pronephric duct, which does not reach the outside of the embryo. Thus the pronephros is
considered nonfunctional in mammals because it cannot excrete waste from the embryo.

Mesonephros
Main article: Mesonephros
Each pronephric duct grows towards the tail of the embryo, and in doing so induces
intermediate mesoderm in the thoracolumbar area to become epithelial tubules called
mesonephric tubules. Each mesonephric tubule receives a blood supply from a branch of
the aorta, ending in a capillary tuft analogous to the glomerulus of the definitive nephron.
The mesonephric tubule forms a capsule around the capillary tuft, allowing for filtration
of blood. This filtrate flows through the mesonephric tubule and is drained into the
continuation of the pronephric duct, now called the mesonephric duct or Wolffian duct.
The nephrotomes of the pronephros degenerate while the mesonephric duct extends
towards the most caudal end of the embryo, ultimately attaching to the cloaca. The
mammalian mesonephros is similar to the kidneys of aquatic amphibians and fishes.

Metanephros

During the fifth week of gestation, the mesonephric duct develops an outpouching, the
ureteric bud, near its attachment to the cloaca. This bud, also called the metanephrogenic
diverticulum, grows posteriorly and towards the head of the embryo. The elongated stalk
of the ureteric bud, the metanephric duct, later forms the ureter. As the cranial end of the
bud extends into the intermediate mesoderm, it undergoes a series of branchings to form
the collecting duct system of the kidney. It also forms the major and minor calyces and
the renal pelvis.
The portion of undifferentiated intermediate mesoderm in contact with the tips of the
branching ureteric bud is known as the metanephrogenic blastema. Signals released from
the ureteric bud induce the differentiation of the metanephrogenic blastema into the renal
tubules. As the renal tubules grow, they come into contact and join with connecting
tubules of the collecting duct system, forming a continuous passage for flow from the
renal tubule to the collecting duct. Simultaneously, precursors of vascular endothelial
cells begin to take their position at the tips of the renal tubules. These cells differentiate
into the cells of the definitive glomerulus.

Terms

Microscopic photograph of the renal cortex.

Microscopic photograph of the renal medulla.

renal capsule: The membranous covering of the kidney.
cortex: The outer layer over the internal medulla. It contains blood vessels,
glomeruli (which are the kidneys' "filters") and urine tubes and is supported by a
fibrous matrix.
hilus: The opening in the middle of the concave medial border for nerves and
blood vessels to pass into the renal sinus.
renal column: The structures which support the cortex. They consist of lines of
blood vessels and urinary tubes and a fibrous material.
renal sinus: The cavity which houses the renal pyramids.

calyces: The recesses in the internal medulla which hold the pyramids. They are
used to subdivide the sections of the kidney. (singular - calyx)
papillae: The small conical projections along the wall of the renal sinus. They
have openings through which urine passes into the calyces. (singular - papilla)
renal pyramids: The conical segments within the internal medulla. They contain
the secreting apparatus and tubules and are also called malpighian pyramids.
renal artery: Two renal arteries come from the aorta, each connecting to a
kidney. The artery divides into five branches, each of which leads to a ball of
capillaries. The arteries supply (unfiltered) blood to the kidneys. The left kidney
receives about 60% of the renal bloodflow.
renal vein: The filtered blood returns to circulation through the renal veins which
join into the inferior vena cava.
renal pelvis: Basically just a funnel, the renal pelvis accepts the urine and
channels it out of the hilus into the ureter.
ureter: A narrow tube 40 cm long and 4 mm in diameter. Passing from the renal
pelvis out of the hilus and down to the bladder. The ureter carries urine from the
kidneys to the bladder by means of peristalsis.
renal lobe: Each pyramid together with the associated overlying cortex forms a
renal lobe

Diseases and disorders

Congenital

Congenital hydronephrosis
Congenital obstruction of urinary tract
Duplicated ureter
Horseshoe kidney
Polycystic kidney disease
Renal dysplasia
Unilateral small kidney
Multicystic dysplastic kidney

Acquired

drawing of an enlarged kidney by John Hunter

Diabetic nephropathy
Glomerulonephritis
Hydronephrosis is the enlargement of one or both of the kidneys caused by
obstruction of the flow of urine.
Interstitial nephritis

Kidney stones are a relatively common and particularly painful disorder.

Kidney tumors
o Wilms tumor
o Renal cell carcinoma
Lupus nephritis
Minimal change disease
In nephrotic syndrome, the glomerulus has been damaged so that a large amount
of protein in the blood enters the urine. Other frequent features of the nephrotic
syndrome include swelling, low serum albumin, and high cholesterol.
Pyelonephritis is infection of the kidneys and is frequently caused by
complication of a urinary tract infection.
Renal failure
o Acute renal failure
o Stage 5 Chronic Kidney Disease

The failing kidney

Generally, humans can live normally with just one kidney, as one has more functioning
renal tissue than is needed to survive, possibly due to the nature of the prehistoric human
diet. Only when the amount of functioning kidney tissue is greatly diminished will Stage
5 Chronic Kidney Disease develop. If the glomerular filtration rate (a measure of renal
function) has fallen very low ( Stage 5 Chronic Kidney Disease), or if the renal
dysfunction leads to severe symptoms, then renal replacement therapy is indicated, either
dialysis or kidney transplantation.

Medical terminology

Medical terms related to the kidneys involve the prefixes renal- and nephro-.
Surgical removal of the kidney is a nephrectomy, while a radical nephrectomy is
removal of the kidney, its surrounding tissue, lymph nodes, and potentially the
adrenal gland. A radical nephrectomy is performed for the removal of the cancers.

Histology
Human cell types found in the kidney include:

Kidney glomerulus parietal cell

Kidney glomerulus podocyte
Kidney proximal tubule brush border cell
Loop of Henle thin segment cell
Thick ascending limb cell
Kidney distal tubule cell
Kidney collecting duct cell
o Cortical collecting duct cell
o Medullary collecting duct cell
Interstitial kidney cell, which do not participate in the filtration process.[4]

Animal kidneys as food

The kidneys of animals can be cooked and eaten by humans (along with other offal). If
prepared properly, they can be nutritious and pleasant tasting. Veal kidneys and lamb
kidneys are particularly prized for their tenderness and flavour. Kidneys can be grilled or
sauted, though they become tough and unpleasant if overcooked.
Diseases and Conditions of the Kidney?
Some of the most common kidney diseases and conditions are: polycystic kidney
disease, nephrosis, lupus nephritis, diabetic nephropathy, rhabdomyolysis, kidney
stones, and renal tubular acidosis.
Polycystic kidney disease (PKD) is an inherited disease characterized by the
growth of numerous cysts filled with fluid in the kidneys.
Nephrosis is a kidney disease characterized by lesions of the epithelial lining of the
renal tubules. The lesions cause a disturbance in the filtration function of the kidney.
As a result, large amounts of protein is found in the urine.
Lupus nephritis is an inflammation of the kidney caused by systemic lupus
erythematosus (SLE), a disease of the immune system.

Diabetic Nephropathy is a kidney condition that occurs only in people with diabetes
mellitus. It results in progressive damage to the small filtering units of the kidney
(glomeruli). About 20-30% of people with diabetes develop diabetic nephropathy.
Glomerulonephritis is a type of kidney disease caused by inflammation of the internal
kidney structures.
Pyelonephritis is an infection of the kidney and the ureters.
Rhabdomyolysis is a disorder involving injury to the kidney. It has been linked to the
drug crestor.
A kidney stone is a hard mass developed from crystals that separate from the urine
and build up on the inner surfaces of the kidney. Kidney stones occur in roughly one
in 10 people in the United States. Once a person gets more than one stone, others
are likely to develop.
Renal tubular acidosis (RTA) is a disease that occurs when the kidneys fail to excrete
acids into the urine, which causes a person's blood to remain too acidic.