# Human Physiology/The Urinary System

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## Introduction

The **Urinary System** is a group of organs in the body concerned with
filtering out excess fluid and other substances from the bloodstream.
The substances are filtered out from the body in the form of **urine**.
Urine is a liquid produced by the kidneys, collected in the bladder and
excreted through the urethra. Urine is used to extract excess minerals
or vitamins as well as blood corpuscles from the body. The Urinary
organs include the kidneys, ureters, bladder, and urethra. The Urinary
system works with the other systems of the body to help maintain
homeostasis. The kidneys are the main organs of homeostasis because they
maintain the acid base balance and the water salt balance of the blood.

## Functions of the Urinary System

One of the major functions of the Urinary system is the process of
excretion. Excretion is the process of eliminating, from an organism,
waste products of metabolism and other materials that are of no use. The
urinary system maintains an appropriate fluid volume by regulating the
amount of water that is excreted in the urine. Other aspects of its
function include regulating the concentrations of various electrolytes
in the body fluids and maintaining normal pH of the blood. Several body
organs carry out excretion, but the kidneys are the most important
excretory organ. The primary function of the kidneys is to maintain a
stable internal environment (homeostasis) for optimal cell and tissue
metabolism. They do this by separating urea, mineral salts, toxins, and
other waste products from the blood. They also do the job of conserving
water, salts, and electrolytes. At least one kidney must function
properly for life to be maintained. **Six important roles of the kidneys
are:**

**Regulation of plasma ionic composition.** Ions such as sodium,
potassium, calcium, magnesium, chloride, bicarbonate, and phosphates are
regulated by the amount that the kidney excretes.

**Regulation of plasma osmolarity.** The kidneys regulate osmolarity
because they have direct control over how many ions and how much water a
person excretes.

**Regulation of plasma volume.** Your kidneys are so important they even
have an effect on your blood pressure. The kidneys control plasma volume
by controlling how much water a person excretes. The plasma volume has a
direct effect on the total blood volume, which has a direct effect on
your blood pressure. Salt(NaCl)will cause osmosis to happen; the
diffusion of water into the blood.

**Regulation of plasma hydrogen ion concentration (pH).** The kidneys
partner up with the lungs and they together control the pH. The kidneys
have a major role because they control the amount of bicarbonate
excreted or held onto. The kidneys help maintain the blood Ph mainly by
excreting hydrogen ions and reabsorbing bicarbonate ions as needed.

**Removal of metabolic waste products and foreign substances from the
plasma.** One of the most important things the kidneys excrete is
nitrogenous waste. As the liver breaks down amino acids it also releases
ammonia. The liver then quickly combines that ammonia with carbon
dioxide, creating **urea** which is the primary nitrogenous end product
of metabolism in humans. The liver turns the ammonia into urea because
it is much less toxic. We can also excrete some ammonia, creatinine and
uric acid. The **creatinine** comes from the metabolic breakdown of
creatine phospate (a high-energy phosphate in muscles). **Uric acid**
comes from the break down of nucleotides. Uric acid is insoluble and too
much uric acid in the blood will build up and form crystals that can
collect in the joints and cause gout.

**Secretion of Hormones** The endocrine system has assistance from the
kidney\'s when releasing hormones. Renin is released by the kidneys.
Renin leads to the secretion of aldosterone which is released from the
adrenal cortex. Aldosterone promotes the kidneys to reabsorb the sodium
(Na+) ions. The kidneys also secrete erythropoietin when the blood
doesn\'t have the capacity to carry oxygen. Erythropoietin stimulates
red blood cell production. The Vitamin D from the skin is also activated
with help from the kidneys. Calcium (Ca+) absorption from the digestive
tract is promoted by vitamin D.

**CC: Chapter Check: Name the role of the kidneys and how they work?**

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## Organs in the Urinary System

### Kidneys And Their Structure

!Kidney Diagram: 1. Renal pyramid 2. Interlobar artery 3. Renal artery
4. Renal vein 5. Renal hylum 6. Renal pelvis 7. Ureter 8. Minor calyx 9.
Renal capsule 10. Inferior renal capsule 11. Superior renal capsule 12.
Interlobar vein 13. Nephron 14. Minor calyx 15. Major calyx 16. Renal
papilla 17. Renal
column{width="250"}

The **kidneys** are a pair of bean shaped, brown organs about the size
of your fist.It measures 10-12 cm long. They are covered by the renal
capsule, which is a tough capsule of fibrous connective tissue. Adhering
to the surface of each kidney is two layers of fat to help cushion them.
There is a concaved side of the kidney that has a depression where a
renal artery enters, and a renal vein and a ureter exit the kidney. The
kidneys are located at the rear wall of the abdominal cavity just above
the waistline, and are protected by the ribcage. They are considered
retroperitoneal, which means they lie behind the peritoneum. There are
three major regions of the kidney, **renal cortex**, **renal medulla**
and the **renal pelvis**. The outer, granulated layer is the renal
cortex. The cortex stretches down in between a radially striated inner
layer. The inner radially striated layer is the renal medulla. This
contains pyramid shaped tissue called the renal pyramids, separated by
renal columns. The ureters are continuous with the renal pelvis and is
the very center of the kidney.

#### Renal Vein

The **renal veins** are veins that drain the kidney. They connect the
kidney to the inferior vena cava. Because the inferior vena cava is on
the right half of the body, the left renal vein is generally the longer
of the two. Unlike the right renal vein, the left renal vein often
receives the left gonadal vein (left testicular vein in males, left
ovarian vein in females). It frequently receives the left suprarenal
vein as well.

#### Renal Artery

The **renal arteries** normally arise off the abdominal aorta and supply
the kidneys with blood. The arterial supply of the kidneys are variable
and there may be one or more renal arteries supplying each kidney. Due
to the position of the aorta, the inferior vena cava and the kidneys in
the body, the right renal artery is normally longer than the left renal
artery. The right renal artery normally crosses posteriorly to the
inferior vena cava. The renal arteries carry a large portion of the
total blood flow to the kidneys. Up to a third of the total cardiac
output can pass through the renal arteries to be filtered by the
kidneys.

### Ureters

The **ureters** are two tubes that drain urine from the kidneys to the
bladder. Each ureter is a muscular tube about 10 inches (25 cm) long.
Muscles in the walls of the ureters send the urine in small spurts into
the bladder, (a collapsible sac found on the forward part of the cavity
of the bony pelvis that allows temporary storage of urine). After the
urine enters the bladder from the ureters, small folds in the bladder
mucosa act like valves preventing backward flow of the urine. The outlet
of the bladder is controlled by a sphincter muscle. A full bladder
stimulates sensory nerves in the bladder wall that relax the sphincter
and allow release of the urine. However, relaxation of the sphincter is
also in part a learned response under voluntary control. The released
urine enters the urethra.

### Urinary Bladder

The **urinary bladder** is a hollow, muscular and distendible or elastic
organ that sits on the pelvic floor (superior to the prostate in males).
On its anterior border lies the pubic symphysis and, on its posterior
border, the vagina (in females) and rectum (in males). The urinary
bladder can hold approximately 17 to 18 ounces (500 to 530 ml) of urine,
however the desire to micturate is usually experienced when it contains
about 150 to 200 ml. When the bladder fills with urine (about half
full), stretch receptors send nerve impulses to the spinal cord, which
then sends a reflex nerve impulse back to the sphincter (muscular valve)
at the neck of the bladder, causing it to relax and allow the flow of
urine into the urethra. The Internal urethral sphincter is involuntary.
The ureters enter the bladder diagonally from its dorsolateral floor in
an area called the trigone. The trigone is a triangular shaped area on
the postero-inferior wall of the bladder. The urethra exits at the
lowest point of the triangle of the trigone. The urine in the bladder
also helps regulate body temperature. A bladder when operating normally
empties completely upon a complete discharge, otherwise it is a sign
that its elasticity is compromised, when it becomes completely void of
fluid, it may cause a chilling sensation due to the rapid change of body
temperature.

### Urethra

!250 px\|thumb\|left\|Female urethra (labeled at bottom
right.)")
!200 px\|thumb\|right\|Male Sphincter urethrae muscle - The male
urethra laid open on its anterior (upper) surface. (Region visible, but
muscle not
labeled.) surface. (Region visible, but muscle not labeled.)")

The **urethra** is a muscular tube that connects the bladder with the
outside of the body. The function of the urethra is to remove urine from
the body. It measures about 1.5 inches (3.8 cm) in a woman but up to 8
inches (20 cm) in a man. Because the urethra is so much shorter in a
woman it makes it much easier for a woman to get harmful bacteria in her
bladder this is commonly called a bladder infection or a UTI. The most
common bacteria of a UTI is E-coli from the large intestines that have
been excreted in fecal matter. **Female urethra**

In the human female, the urethra is about 1-2 inches long and opens in
the vulva between the clitoris and the vaginal opening.

Men have a longer urethra than women. This means that women tend to be
more susceptible to infections of the bladder (cystitis) and the urinary
tract.

**Male urethra**

In the human male, the urethra is about 8 inches long and opens at the
end of the head of the penis.

The length of a male\'s urethra, and the fact it contains a number of
bends, makes catheterisation more difficult.

The **urethral sphincter** is a collective name for the muscles used to
control the flow of urine from the urinary bladder. These muscles
surround the urethra, so that when they contract, the urethra is closed.

-   There are two distinct areas of muscle: the internal sphincter, at
    the bladder neck and
-   the external, or distal, sphincter.

Human males have much stronger sphincter muscles than females, meaning
that they can retain a large amount of urine for twice as long, as much
as 800mL, i.e. \"hold it\".

### Nephrons

A nephron is the basic structural and functional unit of the kidney. The
name nephron comes from the Greek word (nephros) meaning kidney. Its
chief function is to regulate water and soluble substances by filtering
the blood, reabsorbing what is needed and excreting the rest as urine.
Nephrons eliminate wastes from the body, regulate blood volume and
pressure, control levels of electrolytes and metabolites, and regulate
blood pH. Its functions are vital to life and are regulated by the
endocrine system by hormones such as antidiuretic hormone, aldosterone,
and parathyroid hormone.

Each nephron has its own supply of blood from two capillary regions from
the renal artery. Each nephron is composed of an initial filtering
component (the renal corpuscle) and a tubule specialized for
reabsorption and secretion (the renal tubule). The renal corpuscle
filters out large solutes from the blood, delivering water and small
solutes to the renal tubule for modification.

#### Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from
an afferent arteriole of the renal circulation. The glomerular blood
pressure provides the driving force for fluid and solutes to be filtered
out of the blood and into the space made by Bowman\'s capsule. The
remainder of the blood not filtered into the glomerulus passes into the
narrower efferent arteriole. It then moves into the vasa recta, which
are collecting capillaries intertwined with the convoluted tubules
through the interstitial space, where the reabsorbed substances will
also enter. This then combines with efferent venules from other nephrons
into the renal vein, and rejoins with the main bloodstream.

**Afferent/Efferent Arterioles**

The afferent arteriole supplies blood to the glomerulus. A group of
specialized cells known as **juxtaglomerular cells** are located around
the afferent arteriole where it enters the renal corpuscle. The efferent
arteriole drains the glomerulus. Between the two arterioles lies
specialized cells called the **macula densa.** The juxtaglomerular cells
and the macula densa collectively form the **juxtaglomerular
apparatus.** It is in the juxtaglomerular apparatus cells that the
enzyme **renin** is formed and stored. Renin is released in response to
decreased blood pressure in the afferent arterioles, decreased sodium
chloride in the distal convoluted tubule and sympathetic nerve
stimulation of receptors (beta-adrenic) on the juxtaglomerular cells.
Renin is needed to form Angiotensin I and Angiotensin II which stimulate
the secretion of aldosterone by the adrenal cortex.

#### Glomerular Capsule or Bowman\'s Capsule

**Bowman\'s capsule** (also called the **glomerular capsule**) surrounds
the glomerulus and is composed of visceral (simple squamous epithelial
cells) (inner) and parietal (simple squamous epithelial cells) (outer)
layers. The visceral layer lies just beneath the thickened glomerular
basement membrane and is made of podocytes which send foot processes
over the length of the glomerulus. Foot processes interdigitate with one
another forming filtration slits that, in contrast to those in the
glomeruluar endothelium, are spanned by diaphragms. The size of the
filtration slits restricts the passage of large molecules (e.g.,
albumin) and cells (e.g., red blood cells and platelets). In addition,
foot processes have a negatively-charged coat (glycocalyx) that limits
the filtration of negatively-charged molecules, such as albumin. This
action is called electrostatic repulsion.

The parietal layer of Bowman\'s capsule is lined by a single layer of
squamous epithelium. Between the visceral and parietal layers is
Bowman\'s space, into which the filtrate enters after passing through
the podocytes\' filtration slits. It is here that smooth muscle cells
and macrophages lie between the capillaries and provide support for
them. Unlike the visceral layer, the parietal layer does not function in
filtration. Rather, the filtration barrier is formed by three
components: the diaphragms of the filtration slits, the thick glomerular
basement membrane, and the glycocalyx secreted by podocytes. 99% of
glomerular filtrate will ultimately be reabsorbed.

The process of filtration of the blood in the Bowman\'s capsule is
ultrafiltration (or glomerular filtration), and the normal rate of
filtration is 125 ml/min, equivalent to ten times the blood volume
daily. Measuring the glomerular filtration rate (GFR) is a diagnostic
test of kidney function. A decreased GFR may be a sign of renal failure.
Conditions that can affect GFR include: arterial pressure, afferent
arteriole constriction, efferent arteriole constriction, plasma protein
concentration and colloid osmotic pressure.

Any proteins that are roughly 30 kilodaltons or under can pass freely
through the membrane. Although, there is some extra hindrance for
negatively charged molecules due to the negative charge of the basement
membrane and the podocytes. Any small molecules such as water, glucose,
salt (NaCl), amino acids, and urea pass freely into Bowman\'s space, but
cells, platelets and large proteins do not. As a result, the filtrate
leaving the Bowman\'s capsule is very similar to blood plasma in
composition as it passes into the proximal convoluted tubule. Together,
the glomerulus and Bowman\'s capsule are called the renal corpuscle.

#### Proximal Convoluted Tubule (PCT)

The proximal tubule can be anatomically divided into two segments: the
proximal convoluted tubule and the proximal straight tubule. The
proximal convoluted tubule can be divided further into S1 and S2
segments based on the histological appearance of it\'s cells. Following
this naming convention, the proximal straight tubule is commonly called
the S3 segment. The proximal convoluted tubule has one layer of cuboidal
cells in the lumen. This is the only place in the nephron that contains
cuboidal cells. These cells are covered with millions of microvilli. The
microvilli serve to increase surface area for reabsorption.

Fluid in the filtrate entering the proximal convoluted tubule is
reabsorbed into the peritubular capillaries, including approximately
two-thirds of the filtered salt and water and all filtered organic
solutes (primarily glucose and amino acids). This is driven by sodium
transport from the lumen into the blood by the Na+/K+ ATPase in the
basolateral membrane of the epithelial cells. Much of the mass movement
of water and solutes occurs in between the cells through the tight
junctions, which in this case are not selective.

The solutes are absorbed isotonically, in that the osmotic potential of
the fluid leaving the proximal tubule is the same as that of the initial
glomerular filtrate. However, glucose, amino acids, inorganic phosphate,
and some other solutes are reabsorbed via secondary active transport
through cotransport channels driven by the sodium gradient out of the
nephron.

#### Loop of the Nephron or Loop of Henle

!The Nephron Loop or Loop of
Henle.{width="450"}

The loop of Henle (sometimes known as the nephron loop) is a U-shaped
tube that consists of a descending limb and ascending limb. It begins in
the cortex, receiving filtrate from the proximal convoluted tubule,
extends into the medulla, and then returns to the cortex to empty into
the distal convoluted tubule. Its primary role is to concentrate the
salt in the interstitium, the tissue surrounding the loop.

Descending limb:Its descending limb is permeable to water but completely impermeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate. Longer descending limbs allow more time for water to flow out of the filtrate, so longer limbs make the filtrate more hypertonic than shorter limbs.

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Ascending limb:Unlike the descending limb, the ascending limb of Henle\'s loop is impermeable to water, a critical feature of the countercurrent exchange mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its sodium content. This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex.

#### Distal Convoluted Tubule (DCT)

The distal convoluted tubule is similar to the proximal convoluted
tubule in structure and function. Cells lining the tubule have numerous
mitochondria, enabling active transport to take place by the energy
supplied by ATP. Much of the ion transport taking place in the distal
convoluted tubule is regulated by the endocrine system. In the presence
of parathyroid hormone, the distal convoluted tubule reabsorbs more
calcium and excretes more phosphate. When aldosterone is present, more
sodium is reabsorbed and more potassium excreted. Atrial natriuretic
peptide causes the distal convoluted tubule to excrete more sodium. In
addition, the tubule also secretes hydrogen and ammonium to regulate pH.
After traveling the length of the distal convoluted tubule, only 3% of
water remains, and the remaining salt content is negligible. 97.9% of
the water in the glomerular filtrate enters the convoluted tubules and
collecting ducts by osmosis.

#### Collecting ducts

Each distal convoluted tubule delivers its filtrate to a system of
collecting ducts, the first segment of which is the connecting tubule.
The collecting duct system begins in the renal cortex and extends deep
into the medulla. As the urine travels down the collecting duct system,
it passes by the medullary interstitium which has a high sodium
concentration as a result of the loop of Henle\'s countercurrent
multiplier system. Though the collecting duct is normally impermeable to
water, it becomes permeable in the presence of antidiuretic hormone
(ADH). As much as three-fourths of the water from urine can be
reabsorbed as it leaves the collecting duct by osmosis. Thus the levels
of ADH determine whether urine will be concentrated or dilute.
Dehydration results in an increase in ADH, while water sufficiency
results in low ADH allowing for diluted urine. Lower portions of the
collecting duct are also permeable to urea, allowing some of it to enter
the medulla of the kidney, thus maintaining its high ion concentration
(which is very important for the nephron).

Urine leaves the medullary collecting ducts through the renal papilla,
emptying into the renal calyces, the renal pelvis, and finally into the
bladder via the ureter. Because it has a different embryonic origin than
the rest of the nephron (the collecting duct is from endoderm whereas
the nephron is from mesoderm), the collecting duct is usually not
considered a part of the nephron proper.

**Renal Hormones**

1\. Vitamin D- Becomes metabolically active in the kidney. Patients with
renal disease have symptoms of disturbed calcium and phosphate balance.

2\. Erythropoietin- Released by the kidneys in response to decreased
tissue oxygen levels (hypoxia).

3\. Natriuretic Hormone- Released from cardiocyte granules located in
the right atria of the heart in response to increased atrial stretch. It
inhibits ADH secretions which can contribute to the loss of sodium and
water.

## Formation of Urine

Urine is formed in three steps: Filtration, Reabsorption, and Secretion.

### Filtration

Blood enters the afferent arteriole and flows into the glomerulus. Blood
in the glomerulus has both filterable blood components and
non-filterable blood components. Filterable blood components move toward
the inside of the glomerulus while non-filterable blood components
bypass the filtration process by exiting through the efferent arteriole.
Filterable Blood components will then take a plasma like form called
glomerular filtrate. A few of the filterable blood components are water,
nitrogenous waste, nutrients and salts (ions). Nonfilterable blood
components include formed elements such as blood cells and platelets
along with plasma proteins. The glomerular filtrate is not the same
consistency as urine, as much of it is reabsorbed into the blood as the
filtrate passes through the tubules of the nephron.

### Reabsorption

Within the peritubular capillary network, molecules and ions are
reabsorbed back into the blood. Sodium Chloride reabsorbed into the
system increases the osmolarity of blood in comparison to the glomerular
filtrate. This reabsorption process allows water (H2O) to pass from the
glomerular filtrate back into the circulatory system.

Glucose and various amino acids also are reabsorbed into the circulatory
system. These nutrients have carrier molecules that claim the glomerular
molecule and release it back into the circulatory system. If all of the
carrier molecules are used up, excess glucose or amino acids are set
free into the urine. A complication of diabetes is the inability of the
body to reabsorb glucose. If too much glucose appears in the glomerular
filtrate it increases the osmolarity of the filtrate, causing water to
be released into the urine rather than reabsorbed by the circulatory
system. Frequent urination and unexplained thirst are warning signs of
diabetes, due to water not being reabsorbed.

Glomerular filtrate has now been separated into two forms: Reabsorbed
Filtrate and Non-reabsorbed Filtrate. Non-reabsorbed filtrate is now
known as tubular fluid as it passes through the collecting duct to be
processed into urine.

### Secretion

Some substances are removed from blood through the peritubular capillary
network into the distal convoluted tubule or collecting duct. These
substances are Hydrogen ions, creatinine, and drugs. Urine is a
collection of substances that have not been reabsorbed during glomerular
filtration or tubular reabsorbtion.

## Maintaining Water-Salt Balance

It is the job of the kidneys to maintain the water-salt balance of the
blood. They also maintain blood volume as well as blood pressure. Simple
examples of ways that this balance can be changed include ingestion of
water, dehydration, blood loss and salt ingestion.

### Reabsorption of water

Direct control of water excretion in the kidneys is exercised by the
anti-diuretic hormone (ADH), released by the posterior lobe of the
pituitary gland. ADH causes the insertion of water channels into the
membranes of cells lining the collecting ducts, allowing water
reabsorption to occur. Without ADH, little water is reabsorbed in the
collecting ducts and dilute urine is excreted. There are several factors
that influence the secretion of ADH. The first of these happen when the
blood plasma gets too concentrated. When this occurs, special receptors
in the hypothalamus release ADH. When blood pressure falls, stretch
receptors in the aorta and carotid arteries stimulate ADH secretion to
increase volume of the blood.

### Reabsorption of Salt

The Kidneys also regulate the salt balance in the blood by controlling
the excretion and the reabsorption of various ions. As noted above, ADH
plays a role in increasing water reabsorption in the kidneys, thus
helping to dilute bodily fluids. The kidneys also have a regulated
mechanism for reabsorbing sodium in the distal nephron. This mechanism
is controlled by aldosterone, a steroid hormone produced by the adrenal
cortex. Aldosterone promotes the excretion of potassium ions and the
reabsorption of sodium ions. The release of Aldosterone is initiated by
the kidneys. The juxtaglomerular apparatus is a renal structure
consisting of the macula densa, mesangial cells, and juxtaglomerular
cells. Juxtaglomerular cells (JG cells, also known as granular cells)
are the site of renin secretion. Renin is an enzyme that converts
angiotensinogen (a large plasma protein produced by the liver) into
Angiotensin I and eventually into Angiotensin II which stimulates the
adrenal cortex to produce aldosterone. The reabsorption of sodium ions
is followed by the reapsorption of water. This causes blood pressure as
well as blood volume to increase.

**Atrial natriuretic hormone (ANH**) is released by the atria of the
heart when cardiac cells are stretched due to increased blood volume.
ANH inhibits the secretion of renin by the juxtaglomerular apparatus and
the secretion of the aldosterone by the adrenal cortex. This promotes
the excretion of sodium. When sodium is excreted so is water. This
causes blood pressure and volume to decrease.

#### Hypernatremia

An increase in plasma sodium levels above normal is **hypernatremia**.
Sodium is the primary solute in the extracellular fluid. Sodium levels
have a major role in osmolarity regulation. For excitable cells the
electrochemical gradient for sodium across the plasma membrane is
critical for life. Water retention and an increased blood pressure
usually are signs of hypernatremia. If the plasma sodium levels are
below normal it is called **hyponatremia**. Signs of this are low plasma
volume and hypotension.

#### Diuretics

A diuretic (colloquially called a water pill) is any drug that elevates
the rate of bodily urine excretion (diuresis). Diuretics also decrease
the extracellular fluid (ECF) volume, and are primarily used to produce
a negative extracellular fluid balance. Caffeine, cranberry juice and
alcohol are all weak diuretics. In medicine, diuretics are used to treat
heart failure, liver cirrhosis, hypertension and certain kidney
diseases. Diuretics alleviate the symptoms of these diseases by causing
sodium and water loss through the urine. As urine is produced by the
kidney, sodium and water -- which cause edema related to the disease --
move into the blood to replace the volume lost as urine, thereby
reducing the pathological edema. Some diuretics, such as acetazolamide,
help to make the urine more alkaline and are helpful in increasing
excretion of substances such as aspirin in cases of overdose or
poisoning. The antihypertensive actions of some diuretics (thiazides and
loop diuretics in particular) are independent of their diuretic effect.
That is, the reduction in blood pressure is not due to decreased blood
volume resulting from increased urine production, but occurs through
other mechanisms and at lower doses than that required to produce
diuresis. Indapamide was specifically designed with this is mind, and
has a larger therapeutic window for hypertension (without pronounced
diuresis) than most other diuretics. Chemically, diuretics are a diverse
group of compounds that either stimulate or inhibit various hormones
that naturally occur in the body to regulate urine production by the
kidneys. Alcohol produces diuresis through modulation of the vasopressin
system.

## Diseases of the Kidney

**Diabetic nephropathy** (nephropatia diabetica), also known as
Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a
progressive kidney disease caused by angiopathy of capillaries in the
kidney glomeruli. It is characterized by nodular glomerulosclerosis. It
is due to longstanding diabetes mellitus, and is a prime cause for
dialysis in many Western countries. !An image of a **kidney
stone**. In medicine,
**hematuria** (or \"haematuria\") is the presence of blood in the urine.
It is a sign of a large number of diseases of the kidneys and the
urinary tract, ranging from trivial to lethal.

**Kidney stones**, also known as nephrolithiases, urolithiases or renal
calculi, are solid accretions (crystals) of dissolved minerals in urine
found inside the kidneys or ureters. They vary in size from as small as
a grain of sand to as large as a golf ball. Kidney stones typically
leave the body in the urine stream; if they grow relatively large before
passing (on the order of millimeters), obstruction of a ureter and
distention with urine can cause severe pain most commonly felt in the
flank, lower abdomen and groin. Kidney stones are unrelated to
gallstones.

**Case Study** I was 34 weeks pregnant when I noticed blood in my urine.
I immediately went to my OBGYN where I was told that I had a bladder
infection and given an antibiotic. The next morning I experienced the
most intense pain. I was rushed to the ER where I was told that I had
kidney stones. The doctors explained that there was nothing they could
do as long as I was pregnant. The next 3 weeks of my life were filled
with intense pain and multiple painkillers. After I delivered my baby,
CAT scans were done and I was informed that I had 6 kidney stones. It
took three more weeks for me to pass all of the stones the largest
measuring 5 mm. The stones were tested and I was informed that my body
had been building up calcium due to my pregnancy and this was the cause
of the kidney stones. I continued to have kidney pain for 6 months after
passing the stones. I now live my life on a low calcium diet and the
hope that my body will not develop more kidney stones.

**Pyelonephritis** When an infection of the renal pelvis and calices,
called pyelitis, spreads to involve the rest of the kidney as well, the
result is pyelonephritis. It usually results from the spread of fecal
bacterium Escherichia coli from the anal region superiorly through the
urinary tract. In severe cases, the kidney swells and scars, abscesses
form, and the renal pelvis fills with pus. Left untreated, the infected
kidney may be severely damaged, but administration of antibiotics
usually achieve a total cure.

**glomerulonephritis** Inflammation of the glomerular can be caused by
immunologic abnormalities, drugs or toxins, vascular disorders, and
systemic diseases. Glomerulonephritis can be acute, chronic or
progressive. Two major changes in the urine are distinctive of
glomerulonephritis: hematuria and proteinuria with albumin as the major
protein. There is also a decrease in urine as there is a decrease in GFR
(glomerular filtration rate). Renal failure is associated with oliguria
(less than 400 ml of urine output per day).

**Renal Failure** Uremia is a syndrome of renal failure and includes
elevated blood urea and creatinine levels. Acute renal failure can be
reversed if diagnosed early. Acute renal failure can be caused by severe
hypotension or severe glomerular disease. Diagnostic tests include BUN
and plasma creatinine level tests. It is considered to be chronic renal
failure if the decline of renal function to less than 25%.

## Diabetes Insipidus

This is caused by the deficiency of or decrease of ADH. The person with
(DI) has the inability to concentrate their urine in water restriction,
in turn they will void up 3 to 20 liters/day. There are two forms of
(DI), neurogenic, and nephrogenic. In nephrogenic (DI) the kidneys do
not respond to ADH. Usually the nephrogenic (DI) is characterized by the
impairment of the urine concentrating capability of the kidney along
with concentration of water. The cause may be a genetic trait,
electrolyte disorder, or side effect of drugs such as lithium. In the
neurogenic (DI), it is usually caused by head injury near the
hypophysisal tract.

## Urinary tract infections (UTI\'s)

The second most common type of bacterial infections seen by health care
providers is UTI\'s. Out of all the bacterias that colonize and cause
urinary tract infections the big gun is *Escherichia coli*. In the
hospital indwelling catheters and straight catheterizing predispose the
opportunity for urinary tract infections. In females there are three
stages in life that predispose urinary tract infections, that is
menarche, manipulation between intercourse, and menopause. However, a
small percentage of men and children will get urinary tract infections.
In men it is usually due to the prostate gland growth which usually
occurs in older age men. In children it can occur 3% to 5% in girls and
1% in boys, uncircumcised boys it is more common than circumcised ones
to have a urinary tract infection, in girls it may be the result of
onset of toilet training, some predispositions for getting urinary tract
infection include family history and urinary tract anomalies. In
neonates urinary tract infections is most common when bacteremia is
present.

## Dialysis and Kidney Transplant

!Plugged into
dialysis{width="200"}

Generally, humans can live normally with just one kidney. Only when the
amount of functioning kidney tissue is greatly diminished will renal
failure develop. If renal function is impaired, various forms of
medications are used, while others are contraindicated. Provided that
treatment is begun early, it may be possible to reverse chronic kidney
failure due to diabetes or high blood pressure. If creatinine clearance
(a measure of renal function) has fallen very low (\"end-stage renal
failure\"), or if the renal dysfunction leads to severe symptoms,
dialysis is commenced. Dialysis is a medical procedure, performed in
various different forms, where the blood is filtered outside of the
body.

Kidney transplantation is the only cure for end stage renal failure;
dialysis, is a supportive treatment; a form of \"buying time\" to bridge
the inevitable wait for a suitable organ.

The first successful kidney transplant was announced on March 4, 1954 at
Peter Bent Brigham Hospital in Boston. The surgery was performed by Dr.
Joseph E. Murray, who was awarded the Nobel Prize in Medicine in 1990
for this feat.

There are two types of kidney transplants: living donor transplant and a
cadaveric (dead donor) transplant. When a kidney from a living donor,
usually a blood relative, is transplanted into the patient\'s body, the
donor\'s blood group and tissue type must be judged compatible with the
patient\'s, and extensive medical tests are done to determine the health
of the donor. Before a cadaveric donor\'s organs can be transplanted, a
series of medical tests have to be done to determine if the organs are
healthy. Also, in some countries, the family of the donor must give its
consent for the organ donation. In both cases, the recipient of the new
organ needs to take drugs to suppress their immune system to help
prevent their body from rejecting the new kidney.

## Review Questions

Answers for these questions can be found here

1\. While reading a blood test I notice a high level of creatinine, I
could assume from this that

:   A\) There is a possibility of a UTI
:   B\) There is a possibility of diabetes
:   C\) There is a possibility of kidney failure
:   D\) There is nothing wrong, this is normal

2\. Direct control of water excretion in the kidneys is controlled by

:   A\) Anti-diuretic hormone
:   B\) The medulla oblongata
:   C\) Blood plasma
:   D\) Sodium amounts in the blood

3\. Nephrons

:   A\) Eliminate wastes from the body
:   B\) Regulate blood volume and pressure
:   C\) Control levels of electrolytes and metabolites
:   D\) Regulate blood pH
:   E\) All of the above

4\. If I am dehydrated, my body will increase

:   A\) ATP
:   B\) ADP
:   C\) Diluted urine
:   D\) ADH

5\. Which part of the nephron removes water, ions and nutrients from the
blood?

:   A ) vasa recta
:   B ) loop of henle
:   C ) proximal convoluted tubule
:   D ) peritubular capillaries
:   E ) glomerulus

6\. Kidneys have a direct effect on which of the following

:   A ) Blood pressure
:   B ) How much water a person excretes
:   C ) Total blood volume
:   D ) pH
:   E ) all of the above

7\. Why do substances in the glomerulus enter the Bowman\'s capsule?

:   A ) the magnetic charge of the Bowman\'s capsule attracts the
    substances
:   B ) the substances are actively transported into the Bowman\'s
    capsule
:   C ) blood pressure of the glomerulus is so great that most
    substances in blood move into capsule
:   D ) little green men force it in with their ray guns

8\. What happens in tubular excretion?

:   A ) urine bonds are formed between the wastes
:   B ) wastes are diffused from the tubule
:   C ) wastes move into the distal convoluted tubule from the blood
:   D ) blood pressure forces wastes away from the kidney

9\. The countercurrent exchange system
includes\_\_\_\_\_\_\_\_\_and\_\_\_\_\_\_\_\_\_.

:   A ) glomerulus and macula densa
:   B ) proximal convoluted tubule and distal convoluted tubule
:   C ) loop of Henle and collecting tubule
:   D ) afferent arteriole and efferent arteriole
:   E ) ureters and bladder

10\. The function of the loop of the nephron in the process of urine
formation is:

:   A ) reabsorption of water
:   B ) production of filtrate
:   C ) reabsorption of solutes
:   D ) secretion of solutes

11\. Name the six important roles of the kidneys.

## Glossary

**Antidiuretic:** lessening or decreasing of urine production or an
agent that decreases the release of urine.

**Catheterisation:** a catheter is a tube that can be inserted into a
body cavity, duct or vessel. Catheters thereby allow drainage or
injection of fluids or access by surgical instruments. The process of
inserting a catheter is catheterisation. In most uses a catheter is a
thin, flexible tube: a \"soft\" catheter; in some uses, it is a larger,
solid tube: a \"hard\" catheter.

**Dehydration:** condition resulting from excessive loss of body fluid.

**Diabetes:** a general term for a disease characterized by the
beginning stages and onset of renal failure. It is derived from the
Greek word diabaínein, that literally means \"passing through,\" or
\"siphon\", a reference to one of diabetes\' major symptoms---excessive
urine production.

**Diuresis:** secretion and passage of large amounts of urine.

**Diuretic:** increasing of urine production, or an agent that increases
the production of urine.

**Erythropoietin:** hormone that stimulates stem cells in the bone
marrow to produce red blood cells

**Fibrous Capsule:** the kidney\'s loose connective tissue

**Glomerulus:** capillary tuft that receives its blood supply from an
afferent arteriole of the renal circulation.

**Gluconeogenesis:** the cycle of producing a glucose form fat or
protein; preformed by the kidney in times of long fasting, initially
gluconeogenesis is preformed by the liver

**Juxtaglomerular (JG) cells:** Renin-secreting cells that are in
contact with the macula densa and the afferent arterioles of the renal
nephron.

**Juxtaglomerular apparatus (JGA):** A site of juxtaglomerular cells
connecting with the macula densa where renin is secreted and sensor for
control of secretion of golmerular filtration rate.

**Loop of Henle/ Nephron Loop:** u-shaped tube that consists of a
descending limb and ascending limb; primary role is to concentrate the
salt in the interstitium, the tissue surrounding the loop

**Medullary Pyramids or Renal Pyramids:** the cone shaped masses in the
kidney

**Micturition:** another name for excretions

**Nephron:** basic structural and functional unit of the kidney; chief
function is to regulate water and soluble substances by filtering the
blood, reabsorbing what is needed and excreting the rest as urine

**Podocytes:** filtration membrane, in the visceral layer of the
bowman\'s capsule

**Renal Calculi:** kidney stones, solid crystals of dissolved minerals
in urine found inside the kidneys

**Renal Cortex:** outer portion of the kidney

**Renal Lobe:** each pyramid together with the associated overlying
cortex

**Renal Pelvis:** a central space, or cavity that transmits urine to the
urinary bladder via the ureter

**Renin:** hormone released by the Juxtaglomerular (JG) cells of the
kidneys when blood pressure falls

**TURP:** transurethral resection of the prostate. During TURP, an
instrument is inserted up the urethra to remove the section of the
prostate that is blocking urine flow. This is most commonly caused by
benign prostatic hyperplasia (BPH). A TURP usually requires
hospitalization and is done using a general or spinal anesthetic. It is
now the most common surgery used to remove part of an enlarged prostate.

**Urethra:** a muscular tube that connects the bladder with the outside
of the body

**Ureters:** two tubes that drain urine from the kidneys to the bladder

**Urine:** liquid produced by the kidneys, collected in the bladder and
excreted through the urethra

**Urinary Bladder:** a hollow, muscular and distensible or elastic organ
that sits on the pelvic floor

**Urinary System:** a group of organs in the body concerned with
filtering out excess fluid and other substances from the bloodstream

## References

-   Graaff, Van De (2002). \"Human Anatomy, Sixth Edition\". New York:
    McGraw-Hill.
-   Mader, Sylvia S. (2004). *Human Biology*. New York: McGraw-Hill.
-   Smith, Peter (1998). Internet reference,
    \[<http://www.liv.ac.uk/~petesmif/teaching/1bds_mb/notes/homeo/kidney.htm>\|*The
    Role of the Kidney*\]. Department of Clinical Dental Sciences,The
    University of Liverpool.
-   McCance, Katherine L., Heuther, Sue E. (1994). \"Pathophysiology:
    The Biological Basis for Disease In Adults and Children, Second
    Edition\". Mosby-Year Book, Inc.


# Human Physiology/The respiratory system

The **Respiratory System** is vital to every human being. Without it, we
would cease to live outside of the womb. Let us begin by taking a look
at the structure of the respiratory system and how vital it is to life.
During inhalation or exhalation air is pulled towards or away from the
lungs, by several cavities, tubes, and openings.

The organs of the respiratory system make sure that **oxygen** enters
our bodies and **carbon dioxide** leaves our bodies.

The respiratory tract is the path of air from the nose to the lungs. It
is divided into two sections: **Upper Respiratory Tract** and the
**Lower Respiratory Tract**. Included in the upper respiratory tract are
the **Nostrils**, **Nasal Cavities**, **Pharynx**, **Epiglottis**, and
the **Larynx**. The lower respiratory tract consists of the **Trachea**,
**Bronchi**, **Bronchioles**, and the **Lungs**.

As air moves along the respiratory tract it is warmed, moistened and
filtered.

!The **lungs** flank the heart and great vessels in the chest cavity.
`<small>`{=html}(Source: *Gray\'s Anatomy of the Human Body*, 20th ed.
1918.)`</small>`{=html}"){width="230"}

## Functions

In this chapter we will discuss the four processes of respiration. They
are:

1.  **BREATHING** or ventilation
2.  **EXTERNAL RESPIRATION**, which is the exchange of gases (oxygen and
    carbon dioxide) between inhaled air and the blood.
3.  **INTERNAL RESPIRATION**, which is the exchange of gases between the
    blood and tissue fluids.
4.  **CELLULAR RESPIRATION**

In addition to these main processes, the respiratory system serves for:

-   **REGULATION OF BLOOD pH**, which occurs in coordination with the
    kidneys, and as a
-   **DEFENSE AGAINST MICROBES**
-   **Control of body temperature** due to loss of evaporate during
    expiration

## Breathing and Lung Mechanics

**Ventilation** is the exchange of air between the external environment
and the alveoli. Air moves by bulk flow from an area of high pressure to
low pressure. All pressures in the respiratory system are relative to
atmospheric pressure (760mmHg at sea level). Air will move in or out of
the lungs depending on the pressure in the alveoli. The body changes the
pressure in the alveoli by changing the volume of the lungs. As volume
increases pressure decreases and as volume decreases pressure increases.
There are two phases of ventilation; inspiration and expiration. During
each phase the body changes the lung dimensions to produce a flow of air
either in or out of the lungs.

The body is able to stay at the dimensions of the lungs because of the
relationship of the lungs to the thoracic wall. Each lung is completely
enclosed in a sac called the pleural sac. Two structures contribute to
the formation of this sac. The parietal pleura is attached to the
thoracic wall where as the visceral pleura is attached to the lung
itself. In-between these two membranes is a thin layer of intrapleural
fluid. The intrapleural fluid completely surrounds the lungs and
lubricates the two surfaces so that they can slide across each other.
Changing the pressure of this fluid also allows the lungs and the
thoracic wall to move together during normal breathing. Much the way two
glass slides with water in-between them are difficult to pull apart,
such is the relationship of the lungs to the thoracic wall.

The rhythm of ventilation is also controlled by the \"Respiratory
Center\" which is located largely in the medulla oblongata of the brain
stem. This is part of the autonomic system and as such is not controlled
voluntarily (one can increase or decrease breathing rate voluntarily,
but that involves a different part of the brain). While resting, the
respiratory center sends out action potentials that travel along the
phrenic nerves into the diaphragm and the external intercostal muscles
of the rib cage, causing inhalation. Relaxed exhalation occurs between
impulses when the muscles relax. Normal adults have a breathing rate of
12-20 respirations per minute.

### The Pathway of Air

When one breathes air in at sea level, the inhalation is composed of
different gases. These gases and their quantities are Oxygen which makes
up 21%, Nitrogen which is 78%, Carbon Dioxide with 0.04% and others with
significantly smaller portions.

right\|framed\|Diagram of the
**Pharynx**.

In the process of breathing, air enters into the nasal cavity through
the nostrils and is filtered by coarse hairs (*vibrissae*) and mucous
that are found there. The vibrissae filter macroparticles, which are
particles of large size. Dust, pollen, smoke, and fine particles are
trapped in the mucous that lines the **nasal cavities** (hollow spaces
within the bones of the skull that warm, moisten, and filter the air).
There are three bony projections inside the nasal cavity. The
**superior, middle, and inferior nasal conchae**. Air passes between
these conchae via the nasal meatuses.

Air then travels past the nasopharynx, oropharynx, and laryngopharynx,
which are the three portions that make up the pharynx. The
**pharynx** is a funnel-shaped tube that
connects our nasal and oral cavities to the larynx. The **tonsils**
which are part of the lymphatic system, form a ring at the connection of
the oral cavity and the pharynx. Here, they protect against foreign
invasion of antigens. Therefore, the respiratory tract aids the immune
system through this protection. Then the air travels through the
**larynx**. The larynx closes at the epiglottis to prevent the passage
of food or drink as a protection to our trachea and lungs. The larynx is
also our voicebox; it contains vocal cords, in which it produces sound.
Sound is produced from the vibration of the vocal cords when air passes
through them.

The **trachea**, which is also known as our windpipe, has ciliated cells
and mucous secreting cells lining it, and is held open by C-shaped
cartilage rings. One of its functions is similar to the larynx and nasal
cavity, by way of protection from dust and other particles. The dust
will adhere to the sticky mucous and the cilia helps propel it back up
the trachea, to where it is either swallowed or coughed up. The
**mucociliary escalator** extends from the top of the trachea all the
way down to the **bronchioles**, which we will discuss later. Through
the trachea, the air is now able to pass into the bronchi, bronchioles
and finally alveoli before entering the pulmonary capillaries. There is
lots of oxygen and then there is less carbon dioxide when the air comes
in, but when it diffuses, the amounts exchange. All of this happens in
seconds.

### Inspiration

**Inspiration is initiated by contraction of the diaphragm** and in some
cases the intercostals muscles when they receive nervous impulses.
During normal quiet breathing, **the phrenic nerve stimulates the
diaphragm to contract and move downward into the abdomen**. This
downward movement of the diaphragm enlarges the thorax. When necessary,
the intercostal muscles also increase the thorax by contacting and
drawing the ribs upward and outward.

As the diaphragm contracts inferiorly and thoracic muscles pull the
chest wall outwardly, the volume of the thoracic cavity increases. The
lungs are held to the thoracic wall by negative pressure in the pleural
cavity, a very thin space filled with a few millilitres of lubricating
pleural fluid. The negative pressure in the pleural cavity is enough to
hold the lungs open in spite of the inherent elasticity of the tissue.
Hence, as the thoracic cavity increases in volume the lungs are pulled
from all sides to expand, causing a drop in the pressure (a partial
vacuum) within the lung itself (but note that this negative pressure is
still not as great as the negative pressure within the pleural
cavity\--otherwise the lungs would pull away from the chest wall).
Assuming the airway is open, air from the external environment then
follows its pressure gradient down and expands the alveoli of the lungs,
where gas exchange with the blood takes place. As long as pressure
within the alveoli is lower than atmospheric pressure air will continue
to move inwardly, but as soon as the pressure is stabilized air movement
stops.

### Expiration

During quiet breathing, expiration is normally a passive process and
does not require muscles to work (rather it is the result of the muscles
relaxing). When the lungs are stretched and expanded, stretch receptors
within the alveoli send inhibitory nerve impulses to the medulla
oblongata, causing it to stop sending signals to the rib cage and
diaphragm to contract. The muscles of respiration and the lungs
themselves are elastic, so when the diaphragm and intercostal muscles
relax there is an elastic recoil, which creates a positive pressure
(pressure in the lungs becomes greater than atmospheric pressure), and
air moves out of the lungs by flowing down its pressure gradient.

Although the respiratory system is primarily under involuntary control,
and regulated by the medulla oblongata, we have some voluntary control
over it also. This is due to the higher brain function of the cerebral
cortex.

When under physical or emotional stress, more frequent and deep
breathing is needed, and both inspiration and expiration will work as
active processes. Additional muscles in the rib cage forcefully contract
and push air quickly out of the lungs. In addition to deeper breathing,
when coughing or sneezing we exhale forcibly. Our abdominal muscles will
contract suddenly (when there is an urge to cough or sneeze), raising
the abdominal pressure. The rapid increase in pressure pushes the
relaxed diaphragm up against the pleural cavity. This causes air to be
forced out of the lungs.

Another function of the respiratory system is to sing and to speak. By
exerting conscious control over our breathing and regulating flow of air
across the vocal cords we are able to create and modify sounds.

### Lung Compliance

**Lung Compliance** is the magnitude of the change in lung volume
produced by a change in pulmonary pressure. Compliance can be considered
the opposite of stiffness. A low lung compliance would mean that the
lungs would need a greater than average change in intrapleural pressure
to change the volume of the lungs. A high lung compliance would indicate
that little pressure difference in intrapleural pressure is needed to
change the volume of the lungs. More energy is required to breathe
normally in a person with low lung compliance. Persons with low lung
compliance due to disease therefore tend to take shallow breaths and
breathe more frequently.

**Determination of Lung Compliance** Two major things determine lung
compliance. The first is the elasticity of the lung tissue. Any
thickening of lung tissues due to disease will decrease lung compliance.
The second is surface tensions at air water interfaces in the alveoli.
The surface of the alveoli cells is moist. The attractive force, between
the water cells on the alveoli, is called surface tension. Thus, energy
is required not only to expand the tissues of the lung but also to
overcome the surface tension of the water that lines the alveoli.

To overcome the forces of surface tension, certain alveoli cells (Type
II pneumocytes) secrete a protein and lipid complex called
\"\"Surfactant"", which acts like a detergent by disrupting the hydrogen
bonding of water that lines the alveoli, hence decreasing surface
tension.

### Control of respiration

#### Central control

The medulla oblongata is the primary respiratory control center

Its main function is to send signals to the muscles that control
respiration to cause breathing to occur.

#### Peripheral control

CO~2~ is converted to HCO~3~; most CO~2~ produced at the tissue cells is
carried to lungs in the form of HCO~3~

-   CO~2~ & H~2~O form carbonic acid (H~2~CO~3~)
-   changes to H CO~3~ & H+ ions
-   result is H+ ions are buffered by plasma proteins

## Respiratory System: Upper and Lower Respiratory Tracts

For the sake of convenience, we will divide the respiratory system in to
the upper and lower respiratory tracts:

### Upper Respiratory Tract

The upper respiratory tract consists of the nose and the pharynx. Its
primary function is to receive the air from the external environment and
filter, warm, and humidify it before it reaches the delicate lungs where
gas exchange will occur.

Air enters through the nostrils of the nose and is partially filtered by
the nose hairs, then flows into the nasal cavity. The nasal cavity is
lined with epithelial tissue, containing blood vessels, which help warm
the air; and secrete mucous, which further filters the air. The
endothelial lining of the nasal cavity also contains tiny hairlike
projections, called cilia. The *cilia* serve to transport dust and other
foreign particles, trapped in mucous, to the back of the nasal cavity
and to the pharynx. There the mucus is either coughed out, or swallowed
and digested by powerful stomach acids. After passing through the nasal
cavity, the air flows down the pharynx to the larynx.

### Lower Respiratory Tract

The lower respiratory tract starts with the larynx, and includes the
trachea, the two bronchi that branch from the trachea, and the lungs
themselves. This is where gas exchange actually takes place.

1.  Larynx

The larynx (plural larynges), colloquially known as the voice box, is an
organ in our neck involved in protection of the trachea and sound
production. The larynx houses the vocal cords, and is situated just
below where the tract of the pharynx splits into the trachea and the
esophagus. The larynx contains two important structures: the epiglottis
and the vocal cords.

The epiglottis is a flap of cartilage located at the opening to the
larynx. During swallowing, the larynx (at the epiglottis and at the
glottis) closes to prevent swallowed material from entering the lungs;
the larynx is also pulled upwards to assist this process. Stimulation of
the larynx by ingested matter produces a strong cough reflex to protect
the lungs. Note: choking occurs when the epiglottis fails to cover the
trachea, and food becomes lodged in our windpipe.

The vocal cords consist of two folds of connective tissue that stretch
and vibrate when air passes through them, causing vocalization. The
length the vocal cords are stretched determines what pitch the sound
will have. The strength of expiration from the lungs also contributes to
the loudness of the sound. Our ability to have some voluntary control
over the respiratory system enables us to sing and to speak. In order
for the larynx to function and produce sound, we need air. That is why
we can\'t talk when we\'re swallowing.

1.  Trachea
2.  Bronchi
3.  Lungs

## Homeostasis and Gas Exchange

!Gas exchange{width="200"} Homeostasis is
maintained by the respiratory system in two ways: gas exchange and
regulation of blood pH. Gas exchange is performed by the lungs by
eliminating carbon dioxide, a waste product given off by cellular
respiration. As carbon dioxide exits the body, oxygen needed for
cellular respiration enters the body through the lungs. ATP, produced by
cellular respiration, provides the energy for the body to perform many
functions, including nerve conduction and muscle contraction. Lack of
oxygen affects brain function, sense of judgment, and a host of other
problems.

### Gas Exchange

Gas exchange in the lungs and in the alveoli is between the alveolar air
and the blood in the pulmonary capillaries. This exchange is a result of
increased concentration of CO2, and a decrease of oxygen. This process
of exchange is done through diffusion.

### External Respiration

External respiration is the exchange of gas between the air in the
alveoli and the blood within the pulmonary capillaries. A normal rate of
respiration is 12-25 breaths per minute. In external respiration, gases
diffuse in either direction across the walls of the alveoli. Oxygen
diffuses from the air into the blood and carbon dioxide diffuses out of
the blood into the air. Most of the carbon dioxide is carried to the
lungs **in plasma** as bicarbonate ions (HCO3-). When blood enters the
pulmonary capillaries, the bicarbonate ions and hydrogen ions are
converted to carbonic acid (H2CO3) and then back into carbon dioxide
(CO2) and water. This chemical reaction also uses up hydrogen ions. The
removal of these ions gives the blood a more neutral pH, allowing
hemoglobin to bind up more oxygen. De-oxygenated blood \"blue blood\"
coming from the pulmonary arteries, generally has an oxygen partial
pressure (pp) of 40 mmHg and CO2 pp of 45 mmHg. Oxygenated blood leaving
the lungs via the pulmonary veins has an O2 pp of 100 mmHg and CO2 pp of
40 mmHg. It should be noted that alveolar O2 pp is 105 mmHg, and not 100
mmHg. The reason why pulmonary venous return blood has a lower than
expected O2 pp can be explained by \"Ventilation Perfusion Mismatch\".

### Internal Respiration

Internal respiration is the exchanging of gases at the cellular level.

#### The Passage Way From the Trachea to the Bronchioles

There is a point at the inferior portion of the trachea where it
branches into two directions that form the right and left primary
bronchus. This point is called the **Carina** which is the keel-like
cartilage plate at the division point. We are now at the **Bronchial
Tree**. It is named so because it has a series of respiratory tubes that
branch off into smaller and smaller tubes as they run throughout the
lungs.

#### Right and Left Lungs

right\|framed\|Diagram of the
**lungs** The **Right Primary
Bronchus** is the first portion we come to, it then branches off into
the **Lobar (secondary) Bronchi**, **Segmental (tertiary) Bronchi**,
then to the **Bronchioles** which have little cartilage and are lined by
simple cuboidal epithelium (See fig. 1). The bronchi are lined by
pseudostratified columnar epithelium. Objects will likely lodge here at
the junction of the Carina and the Right Primary Bronchus because of the
vertical structure. Items have a tendency to fall in it, where as the
Left Primary Bronchus has more of a curve to it which would make it hard
to have things lodge there.

The **Left Primary Bronchus** has the same setup as the right with the
lobar, segmental bronchi and the bronchioles.

The lungs are attached to the heart and trachea through structures that
are called the **roots of the lungs**. The roots of the lungs are the
bronchi, pulmonary vessels, bronchial vessels, lymphatic vessels, and
nerves. These structures enter and leave at the **hilus** of the lung
which is \"the depression in the medial surface of a lung that forms the
opening through which the bronchus, blood vessels, and nerves pass\"
(medlineplus.gov).

There are a number of **terminal bronchioles** connected to
**respiratory bronchioles** which then advance into the **alveolar
ducts** that then become **alveolar sacs**. Each bronchiole terminates
in an elongated space enclosed by many air sacs called **alveoli** which
are surrounded by blood capillaries. Present there as well, are
**Alveolar Macrophages**, they ingest any microbes that reach the
alveoli. The **Pulmonary Alveoli** are **microscopic**, which means they
can only be seen through a microscope, membranous air sacs within the
lungs. They are units of respiration and the site of gas exchange
between the respiratory and circulatory systems.

### Cellular Respiration

First the oxygen must diffuse from the alveolus into the capillaries. It
is able to do this because the capillaries are permeable to oxygen.
After it is in the capillary, about 5% will be dissolved in the blood
plasma. The other oxygen will bind to red blood cells. The red blood
cells contain hemoglobin that carries oxygen. Blood with hemoglobin is
able to transport 26 times more oxygen than plasma without hemoglobin.
Our bodies would have to work much harder pumping more blood to supply
our cells with oxygen without the help of hemoglobin. Once it diffuses
by osmosis it combines with the hemoglobin to form oxyhemoglobin.

Now the blood carrying oxygen is pumped through the heart to the rest of
the body. Oxygen will travel in the blood into arteries, arterioles, and
eventually capillaries where it will be very close to body cells. Now
with different conditions in temperature and pH (warmer and more acidic
than in the lungs), and with pressure being exerted on the cells, the
hemoglobin will give up the oxygen where it will diffuse to the cells to
be used for cellular respiration, also called aerobic respiration.
Cellular respiration is the process of moving energy from one chemical
form (glucose) into another (ATP), since all cells use ATP for all
metabolic reactions.

It is in the mitochondria of the cells where oxygen is actually consumed
and carbon dioxide produced. Oxygen is produced as it combines with
hydrogen ions to form water at the end of the electron transport chain
(see chapter on cells). As cells take apart the carbon molecules from
glucose, these get released as carbon dioxide. Each body cell releases
carbon dioxide into nearby capillaries by diffusion, because the level
of carbon dioxide is higher in the body cells than in the blood. In the
capillaries, some of the carbon dioxide is dissolved in plasma and some
is taken by the hemoglobin, but most enters the red blood cells where it
binds with water to form carbonic acid. It travels to the capillaries
surrounding the lung where a water molecule leaves, causing it to turn
back into carbon dioxide. It then enters the lungs where it is exhaled
into the atmosphere.

## Lung Capacity

!450 px\|right The normal volume
moved in or out of the lungs during quiet breathing is called **tidal
volume**. When we are in a relaxed state, only a small amount of air is
brought in and out, about 500 mL. You can increase both the amount you
inhale, and the amount you exhale, by breathing deeply. Breathing in
very deeply is **Inspiratory Reserve Volume** and can increase lung
volume by 2900 mL, which is quite a bit more than the tidal volume of
500 mL. We can also increase expiration by contracting our thoracic and
abdominal muscles. This is called **expiratory reserve volume** and is
about 1400 ml of air. **Vital capacity** is the total of tidal,
inspiratory reserve and expiratory reserve volumes; it is called vital
capacity because it is vital for life, and the more air you can move,
the better off you are. There are a number of illnesses that we will
discuss later in the chapter that decrease vital capacity. Vital
Capacity can vary a little depending on how much we can increase
inspiration by expanding our chest and lungs. Some air that we breathe
never even reaches the lungs! Instead it fills our nasal cavities,
trachea, bronchi, and bronchioles. These passages aren\'t used in gas
exchange so they are considered to be **dead air space**. To make sure
that the inhaled air gets to the lungs, we need to breathe slowly and
deeply. Even when we exhale deeply some air is still in the lungs,(about
1000 ml) and is called **residual volume**. This air isn\'t useful for
gas exchange. There are certain types of diseases of the lung where
residual volume builds up because the person cannot fully empty the
lungs. This means that the vital capacity is also reduced because their
lungs are filled with useless air.

## Stimulation of Breathing

There are two pathways of motor neuron stimulation of the respiratory
muscles. The first is the control of voluntary breathing by the cerebral
cortex. The second is involuntary breathing controlled by the medulla
oblongata.

There are chemoreceptors in the aorta, the carotid body of carotid
arteries, and in the medulla oblongata of the brainstem that are
sensitive to pH. As carbon dioxide levels increase there is a buildup of
carbonic acid, which releases hydrogen ions and lowers pH. Thus, the
chemoreceptors do not respond to changes in oxygen levels (which
actually change much more slowly), but to pH, which is dependent upon
plasma carbon dioxide levels. **In other words, CO2 is the driving force
for breathing**. The receptors in the aorta and the carotid sinus
initiate a reflex that immediately stimulates breathing rate and the
receptors in the medulla stimulate a sustained increase in breathing
until blood pH returns to normal.

This response can be experienced by running a 100-meter dash. During
this exertion (or any other sustained exercise) your muscle cells must
metabolize ATP at a much faster rate than usual, and thus will produce
much higher quantities of CO2. The blood pH drops as CO2 levels
increase, and you will involuntarily increase breathing rate very soon
after beginning the sprint. You will continue to breathe heavily after
the race, thus expelling more carbon dioxide, until pH has returned to
normal. Metabolic acidosis therefore is acutely corrected by respiratory
compensation (hyperventilation).

## Regulation of Blood pH

Many of us are not aware of the importance of maintaining the acid/base
balance of our blood. It is vital to our survival. Normal blood pH is
set at 7.4, which is slightly alkaline or \"basic\". If the pH of our
blood drops below 7.2 or rises above 7.6 then very soon our brains would
cease functioning normally and we would be in big trouble. Blood pH
levels below 6.9 or above 7.9 are usually fatal if they last for more
than a short time. Another wonder of our amazing bodies is the ability
to cope with every pH change -- large or small. There are three factors
in this process: the lungs, the kidneys and buffers.

So what exactly is pH? pH is the concentration of hydrogen ions (H+).
Buffers are molecules which take in or release ions in order to maintain
the H+ ion concentration at a certain level. When blood pH is too low
and the blood becomes too acidic (acidosis), the presence of too many H+
ions is to blame. Buffers help to soak up those extra H+ ions. On the
other hand, the lack of H+ ions causes the blood to be too basic
(alkalosis). In this situation, buffers release H+ ions. Buffers
function to maintain the pH of our blood by either donating or grabbing
H+ ions as necessary to keep the number of H+ ions floating around the
blood at just the right amount.

The most important buffer we have in our bodies is a mixture of carbon
dioxide (CO2) and bicarbonate ion (HCO3). CO2 forms carbonic acid
(H2CO3) when it dissolves in water and acts as an acid giving up
hydrogen ions (H+) when needed. HCO3 is a base and soaks up hydrogen
ions (H+) when there are too many of them. In a nutshell, blood pH is
determined by a balance between bicarbonate and carbon dioxide.

**Bicarbonate Buffer System**. With this important system our bodies
maintain homeostasis. (Note that H2CO3 is Carbonic Acid and HCO3 is
Bicarbonate)

CO2 + H2O \<\-\--\> H2CO3 \<\-\--\> (H+) + HCO3

-   If pH is too high, carbonic acid will donate hydrogen ions (H+) and
    pH will drop.
-   If pH is too low, bicarbonate will bond with hydrogen ions (H+) and
    pH will rise.

Too much CO2 or too little HCO3 in the blood will cause acidosis. The
CO2 level is increased when hypoventilation or slow breathing occurs,
such as if you have emphysema or pneumonia. Bicarbonate will be lowered
by ketoacidosis, a condition caused by excess fat metabolism (diabetes
mellitus).

Too much HCO3 or too little CO2 in the blood will cause alkalosis. This
condition is less common than acidosis. CO2 can be lowered by
hyperventilation.

So, in summary, if you are going into respiratory acidosis the above
equation will move to the right. The body\'s H+ and CO2 levels will rise
and the pH will drop. To counteract this the body will breathe more and
release H+. In contrast, if you are going into respiratory alkalosis the
equation will move to the left. The body\'s H+ and CO2 levels will fall
and the pH will rise. So the body will try to breathe less to release
HCO3. You can think of it like a leak in a pipe: where ever there is a
leak, the body will \"fill the hole\".

## Problems Associated With the Respiratory Tract and Breathing

The environment of the lung is very moist, which makes it a hospitable
environment for bacteria. Many respiratory illnesses are the result of
bacterial or viral infection of the lungs. Because we are constantly
being exposed to harmful bacteria and viruses in our environment, our
respiratory health can be adversely affected. There are a number of
illnesses and diseases that can cause problems with breathing. Some are
simple infections, and others are disorders that can be quite serious.

**Carbon Monoxide Poisoning**: caused when carbon monoxide binds to
hemoglobin in place of oxygen. Carbon monoxide binds much tighter,
without releasing, causing the hemoglobin to become unavailable to
oxygen. The result can be fatal in a very short amount of time.

:   Mild Symptoms: flu like symptoms, dizziness, fatigue, headaches,
    nausea, and irregular breathing
:   Moderate Symptoms: chest pain, rapid heart beat, difficulty
    thinking, blurred vision, shortness of breath and unsteadiness
:   Severe Symptoms: seizures, palpitations, disorientation, irregular
    heart beat, low blood pressure, coma and death.

**Pulmonary Embolism:** blockage of the pulmonary artery (or one of its
branches) by a blood clot, fat, air or clumped tumor cells. By far the
most common form of pulmonary embolism is a thromboembolism, which
occurs when a blood clot, generally a venous thrombus, becomes dislodged
from its site of formation and embolizes to the arterial blood supply of
one of the lungs.

:   Symptoms may include difficulty breathing, pain during breathing,
    and more rarely circulatory instability and death. Treatment,
    usually, is with anticoagulant medication.

## Upper Respiratory Tract Infections

The upper respiratory tract consists of our nasal cavities, pharynx, and
larynx. Upper respiratory infections (URI) can spread from our nasal
cavities to our sinuses, ears, and larynx. Sometimes a viral infection
can lead to what is called a secondary bacterial infection.**\"Strep
throat\"** is a primary bacterial infection and can lead to an upper
respiratory infection that can be generalized or even systemic (affects
the body as a whole). Antibiotics aren\'t used to treat viral
infections, but are successful in treating most bacterial infections,
including strep throat. The symptoms of strep throat can be a high
fever, severe sore throat, white patches on a dark red throat, and
stomach ache.

Sinusitis:An infection of the cranial sinuses is called **sinusitis**. Only about 1-3% of URI\'s are accompanied by sinusitis. This \"sinus infection\" develops when nasal congestion blocks off the tiny openings that lead to the sinuses. Some symptoms include: post nasal discharge, facial pain that worsens when bending forward, and sometimes even tooth pain can be a symptom. Successful treatment depends on restoring the proper drainage of the sinuses. Taking a hot shower or sleeping upright can be very helpful. Otherwise, using a spray decongestant or sometimes a prescribed antibiotic will be necessary.

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Otitis Media:Otitis media in an infection of the middle ear. Even though the middle ear is not part of the respiratory tract, it is discussed here because it is often a complication seen in children who has a nasal infection. The infection can be spread by way of the *\'auditory (Eustachian) tube* that leads form the nasopharynx to the middle ear. The main symptom is usually pain. Sometimes though, vertigo, hearing loss, and dizziness may be present. Antibiotics can be prescribed and tubes are placed in the eardrum to prevent the buildup of pressure in the middle ear and the possibility of hearing loss.

!Photo of
**Tonsillitis**.{width="300"}

Tonsillitis:Tonsillitis occurs when the tonsils become swollen and inflamed. The tonsils located in the posterior wall of the nasopharynx are often referred to as adenoids. If you suffer from tonsillitis frequently and breathing becomes difficult, they can be removed surgically in a procedure called a tonsillectomy.

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Laryngitis:An infection of the larynx is called laryngitis. It is accompanied by hoarseness and being unable to speak in an audible voice. Usually, laryngitis disappears with treatment of the URI. Persistent hoarseness without a URI is a warning sign of cancer, and should be checked into by your physician.

{{-}}

## Lower Respiratory Tract Disorders

Lower respiratory tract disorders include infections, restrictive
pulmonary disorders, obstructive pulmonary disorders, and lung cancer.

### Lower Respiratory Infections

Acute bronchitis:An infection that is located in the primary and secondary bronchi is called bronchitis. Most of the time, it is preceded by a viral URI that led to a secondary bacterial infection. Usually, a nonproductive cough turns into a deep cough that will expectorate mucus and sometimes pus.\
Pneumonia:A bacterial or viral infection in the lungs where the bronchi and the alveoli fill with a thick fluid. Usually it is preceded by influenza. Symptoms of pneumonia include high fever & chills, with headache and chest pain. Pneumonia can be located in several lobules of the lung and obviously, the more lobules involved, the more serious the infection. It can be caused by a bacteria that is usually held in check, but due to stress or reduced immunity has gained the upper hand.

### Restrictive Pulmonary Disorders

Pulmonary Fibrosis:Vital capacity is reduced in these types of disorders because the lungs have lost their elasticity. Inhaling particles such as sand, asbestos, coal dust, or fiberglass can lead to **pulmonary fibrosis**, a condition where fibrous tissue builds up in the lungs. This makes it so our lungs cannot inflate properly and are always tending toward deflation. Pulmonary fibrosis can be synonymous with interstitial lung disease (ILD), or interstitial pneumonia or pneumonitis.

### Obstructive Pulmonary Disorders

!400 px\|Diagram of the lungs during an **asthma
attack**.

Asthma:Asthma is a respiratory disease of the bronchi and bronchioles. The symptoms include wheezing, shortness of breath, and sometimes a cough that will expel mucus. The airways are very sensitive to irritants which can include pollen, dust, animal dander, and tobacco. Even being out in cold air can be an irritant. When exposed to an irritant, the smooth muscle in the bronchioles undergoes spasms. Most asthma patients have at least some degree of bronchial inflammation that reduces the diameter of the airways and contributes to the seriousness of the attack.

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Emphysema:Emphysema is a type of chronic obstructive pulmonary disease. Typically characterized by a loss of elasticity and surfactant in the alveoli, a loss of surface area decreases the gas exchange in the lungs. These patients have difficulty with too little expiratory pressure, not retaining inspired air long enough for sufficient gas exchange to happen.

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Chronic Bronchitis:Another type of chronic obstructive pulmonary disease, Chronic Bronchitis is caused by overproduction of mucus in the airways, causing an inadequate expiration of inspired air. Retention of air in the lungs reduces gas exchange at the alveoli, and can lead to a hypoxic drive. These patients are known as \"blue bloaters\", vulnerable to cyanosis and often have increased thoracic diameters.

## Respiratory Distress Syndrome

Pathophysiology

At birth the pressure needed to expand the lungs requires high
inspiratory pressure. In the presence of normal surfactant levels the
lungs retain as much as 40% of the residual volume after the first
breath and thereafter will only require far lower inspiratory pressures.
In the case of deficiency of surfactant the lungs will collapse between
breaths, this makes the infant work hard and each breath is as hard as
the first breath. If this goes on further the pulmonary capillary
membranes become more permeable, letting in fibrin rich fluids between
the alveolar spaces and in turn forms a hyaline membrane. The hyaline
membrane is a barrier to gas exchange, this hyaline membrane then causes
hypoxemia and carbon dioxide retention that in turn will further impair
surfactant production.

Etiology

Type two alveolar cells produce surfactant and do not develop until the
25th to the 28th week of gestation, in this, respiratory distress
syndrome is one of the most common respiratory disease in premature
infants. Furthermore, surfactant deficiency and pulmonary immaturity
together leads to alveolar collapse. Predisposing factors that
contribute to poorly functioning type II alveolar cells in a premature
baby are if the child is a preterm male, white infants, infants of
mothers with diabetes, precipitous deliveries, cesarean section
performed before the 38th week of gestation. Surfactant synthesis is
influenced by hormones, this ranges form insulin and cortisol. Insulin
inhibits surfactant production, explaining why infants of mothers with
diabetes type 1 are at risk of development of respiratory distress
syndrome. Cortisol can speed up maturation of type II cells and
therefore production of surfactant. Finally, in the baby delivered by
cesarean section are at greater risk of developing respiratory distress
syndrome because the reduction of cortisol produced because the lack of
stress that happens during vaginal delivery, hence cortisol increases in
high stress and helps in the maturation of type II cells of the alveoli
that cause surfactant.

Treatment

Today to prevent respiratory distress syndrome are animal sources and
synthetic surfactants, and administrated through the airways by an
endotracheal tube and the surfactant is suspended in a saline solution.
Treatment is initiated post birth and in infants who are at high risk
for respiratory distress syndrome.

## Sleep Apnea

!CPAP is the most common treatment for obstructive sleep
apnea.{width="200"}
Sleep apnea or sleep apnoea is a sleep disorder characterized by pauses
in breathing during sleep. These episodes, called apneas (literally,
\"without breath\"), each last long enough so one or more breaths are
missed, and occur repeatedly throughout sleep. The standard definition
of any apneic event includes a minimum 10 second interval between
breaths, with either a neurological arousal (3-second or greater shift
in EEG frequency, measured at C3, C4, O1, or O2), or a blood oxygen
desaturation of 3-4 percent or greater, or both arousal and
desaturation. Sleep apnea is diagnosed with an overnight sleep test
called polysomnogram. One method of treating central sleep apnea is with
a special kind of CPAP, APAP, or VPAP machine with a Spontaneous Time
(ST) feature. This machine forces the wearer to breathe a constant
number of breaths per minute.

(CPAP), or continuous positive airway pressure, in which a controlled
air compressor generates an airstream at a constant pressure. This
pressure is prescribed by the patient\'s physician, based on an
overnight test or titration.

## Nutrition for COPD (Chronic Obstructive Pulmonary Disease) Patients

Nutrition is particularly important for ventilator-dependent patient.
When metabolizing macronutrients carbon dioxide and water are produced.
The respiratory quotient (RQ) is a ratio of produced carbon dioxide to
amount consumed. Carbohydrates metabolism produces the most amount of
carbon dioxide so they have the highest (RQ). Fats produce the least
amount of carbon dioxide along with proteins. Protein has a slightly
higher RQ ratio. It is recommended that this kind of patient not exceed
a 1.0 respiratory quotient (RQ). Lowering carbohydrates and
supplementing fat or protein in the diet might not result in maintaining
the desired outcome because, excess amounts fat or protein may also
result in a respiratory quotient (RQ) higher than 1.0.

-   Please reference source and fact accuracy. It seems like by
    definition, it is impossible to exceed a respiratory quotient (RQ)
    of 1.0. \*

## Case Study

**Cystic Fibrosis**

This disease is most common in Caucasians and will happen to 1 in every
2500 people. It is most known for its effects on the respiratory tract
although it does effect other systems as well. The respiratory passages
become clogged with a thick mucus that is difficult to expel even with
vigorous coughing. Breathing becomes difficult and affected individuals
run the risk of choking to death on their own secretions unless
strenuous effort is made to clear the lungs multiple times every day.
Victims frequently will die in the 20\'s of pneumonia. All of us secrete
mucus by certain cells in the epithelium that line the respiratory
passageways. In normal cases the cells also secrete a watery fluid that
will dilute the mucus making it easier to pass through the airways. In
cystic fibrosis that secretion of watery fluid is impaired. This makes
the mucus thicker and difficult to clear from the passageways. A 1989
discovery found that cystic fibrosis is caused by defects in a type of
anion channel found in apical membranes of epithelial cells in the
respiratory system and elsewhere[^1]. The defects directly impede the
chloride ion transport, which will then indirectly effect other
exchanges of ions in the cells. This causes the epithelium to not create
the osmotic gradient necessary for water secretion. It has been known
for a long time that cystic fibrosis is caused by a recessive gene
inheritance. This gene codes for the chloride channel protein, which can
malfunction in a variety of ways, each with specific treatment required.

## Glossary

## References

-   Mader, Sylvia S. *Human Biology*. McGraw Hill Publishing, Burr
    Ridge, IL. 2004.
-   Van De Graaff, Kent M. *Human Anatomy*. McGraw Hill Publishing, Burr
    Ridge, IL. 2002.
-   Department of Environmental Biology, University of Adelaide,
    Adelaide, South Australia
-   Wikipedia:Lung
-   Medlineplus.gov. *Hilus*.
    <http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=hilum+>
-   <http://www.an-attorney-for-you.com/legal/carbon-monoxide.htm>
-   www.ineedtoknow.com
-   \'\'\"The respiratory system\"Authors Mary Kitteredge,intro. by C.
    Everett Koop, M.D.,SC.D., foreword by Sandra Thurman

## External Resources

-   Eastern Kentucky University Gary Ritchison Lecture Notes: Human
    Respiration (includes
    videos)
-   In depth anatomy and physiology of the pulmonary
    system.

pt:Fisiologia/Sistema
respiratório

[^1]: Riordan,J.R., Rommens,J.M., Kerem,B., Alon,N., Rozmahel,R.,
    Grzelczak,Z., Zielenski,J., Lok,S., Plavsic,N. and Chou,J.L. (1989)
    Identification of the cystic fibrosis gene: cloning and
    characterization of complementary DNA. Science, 245, 1066--73.