Control of Respiration

There are many things that control breathing!! But the main control of breathing is by the medulla oblongata. If this is damaged, automatic breathing does not occur and you must remember to breathe.

Factors Affecting Breathing, General Guidelines
We breathe to get oxygen to all the cells in our body. The more metabolic activity in a cell the more oxygen it will need (more ATP/energy needed). So thinking about oxygen demand will help you understand what factors effect breathing and whether they increase or decrease activity in the medullary respiratory centers and therefore breathing rate, depth, and rhythm.

When we exercise, we have an increased oxygen demand. This means that not only do the muscle cells need more oxygen, but they also release more carbon dioxide. The carbon dioxide is released from the muscle cells and travels to the blood following its partial pressure gradient. Once in the blood it is combine with water by carbonic anhydrase to form carbonic acid. This makes the blood more acidic which means more H+ ions and a lower pH. So breathing would increase if oxygen levels decrease to or below dangerously low levels ~50-60mmHg (end of plateau region of oxygen-hemoglobin dissociation curve). Also if blood has too much carbon dioxide (measured as too much acidity).

There are many factors that can increase our metabolic rate, or metabolism. Anything that increases this will increase breathing. Anything that is a by product of an increased metabolism also indicates an increase in breathing. For example, our muscles when we exercise also produce lots of heat, so an increase in temperatures would increase breathing rate. An increase in blood acidity or acidosis (due to increased carbon dioxide, or perhaps increased H+ ions such as in diabetes mellitus) would also increase breathing. An interesting factor is increased proprioceptor discharge. Before you exercise, your body prepares for the exercise by increasing signals from proprioceptors in your muscle cells (letting body know position) this leads to an increased breathing rate, so you will have more oxygen and less carbon dioxide in your blood in preparation for the large oxygen demand to come!

Another set of factors that effect breathing have to do with fight or flight type responses (think sympathetic system). Things like pain, cold, and extreme emotions (limbic system, RAS, etc) can cause an increase in breathing rate if chronic (prolonged) or can cause a temporary stopping of breathing if sudden. This has to do with survival instincts.

A similar set of factors that effect breathing have to do with more local control and maintenance of the lungs. For example if you try to breathe in as hard as you can and manage to take in more than 1L of air, your lungs become overstretched, and stretch receptors in your lungs send signals via the vagus nerve (CN10, sends mainly sensory info about viscera to CNS) to the medulla to inhibit inspiration so you don't take in any more air. This prevents you from over-inflating your lungs.

Factors Affecting Breathing, List

• Herring-Breuer Reflex - Stretch of bronchi/bronchiole smooth muscle -> stretch receptors->vagus nerve->inhibition of inspiratory neurons in medulla->diaphragm+ external intercostals relax-> exhale
• Voluntary Control - higher brain centers->primary motor cortex->corticospinal pathway->skeletal muscles of breathing->inhale/exhale
  
• Increased acidity in CSF (cerebrospinal fluid) -> due to increased carbon dioxide which can cross blood brain barrier and once there through carbonic anhydrase become carbonic acid then bicarbonate and H+ -> H+ detected by central chemoreceptors in medulla (easy to detect b/c CSF not buffered well -> increase ventilation
• Increased acidity in arterial blood -> due to increased carbon dioxide in blood, but just as in CSF, H+ ions produced and detected by chemoreceptors, but this time in aortic and carotid bodies of the aorta and carotid arteries (these can also weakly detect actual carbon dioxide levels)-> increase ventilation
• Increased acidity due to diabetes mellitus -> increase ventilation
• Severe decrease in oxygen levels -> described above -> increase ventilation
• Carbon monoxide poisoning -> CO binds to oxygen binding sites on hemoglobin producing carboxyHb, and since it binds 210 times more readily than oxygen it leads to very little oxygen binding. CO is an odorless, colorless gas and since it binds to oxygen binding sites, it doesn't effect the amount of oxygen dissolved in the blood, only the amount of oxygen saturation of Hb (i.e. no change in partial pressure of oxygen or carbon dioxide which are both measures of how much of each gas is dissolved in solutions). This is very dangerous since, there will be no obvious signs of CO poisoning and it is the leading cause of death from fires!
• Temperature, emotion, cold, pain, anal sphincter stretch, proprioceptor discharge -> all of these if increased increase ventilation rate
  
• Blood pressure -> if BP increases then there is lots of oxygen getting to blood and lots of carbon dioxide being removed, so ventilation would decrease (specifically if sudden increase in BP). Also if BP suddenly decreases, ventilation increases.
• Breath holding -> after 4-5 min (amount of time before the 75% saturation of Hb decreases so that no oxygen can be unloaded) -> medulla overrides voluntary control _>breathe
  
  

Physiology of the Respiratory System

There are 3 main processes in respiration:

1. Pulmonary Ventilation
2. External Respiration
3. Internal Respiration

Pulmonary Ventilation is the process of taking in air from the atmosphere into the lungs (inspiration) and then releasing it back to the atmosphere (expiration). The purpose of this is to take in oxygen which is needed by every cell in the body and to release carbon dioxide which is toxic if it builds up in the body. Normally we inspire and expire air quietly, i.e. passively. In this case, we use only two sets of respiratory muscles the diaphragm and external intercostals. When these muscles contract air is taken into the lungs and when they relax air is expelled. To see the anatomy of the external intercostals watch this (from 1:08-1:50). To see the anatomy of the diaphragm watch this.

These two sets of muscles increase the size (volume) of the thoracic cavity when they contract and they decrease its volume when they relax. To understand how this change in volume causes air to be sucked into the lungs or pushed out, we need to understand Boyle's Law:

P * V = k or in more simply, pressure is inversely proportional to volume. This means that if volume increases, pressure decreases, and vice versa.

Another thing to consider is that the lungs are surrounded by a pleural membrane which is a serous membrane (serous b/c it doesn't open to outside) and this membrane is filled with fluid. This is called the pleural cavity.

The pressure-volume relationship in these 3 spaces determines whether air is inhaled or exhaled.

• Patm = 760mmHg -- the pressure in the atmosphere (always)
  
• Ppul = 760mmHg -- this is the pressure in the lungs at rest (between breaths) when no air is moving
• Pip = 756mmHg -- the pressure in the pleural cavity when lungs at rest (no breathing/air movement)

First lets look at inspiration. When the diaphragm and external intercostals contract and increase the volume of the thoracic cavity they pull on the parietal (attached to thoracic wall) portion of the pleural membrane causing the pleaural cavity volume to increase, and since pressure is inversely proportional to volume this decreases the pressure here from 756mmHg to 754mmHg. Now the volume in the pleural cavity increases not only b/c of the pull from the expansion, but also because the visceral portion (attached to lungs) doesn't move when the thoracic cavity expands, i.e. the lungs resist this expansion. However, soon the lungs feel an increased pressure gradient (Ppul>>Pip) and to reduce this difference, the lungs expand. Since an increase in volume means a reduction in pressure, the pressure in the lungs decreases from 760mmHg to 758mmHg. This causes a pressure gradient or difference between the lungs and the atmosphere, so air moves from the area of higher pressure (Patm=760) to the area of lower pressure (Ppul=758) until the there is no longer a pressure gradient, Ppul=Patm.

Expiration is the same process but in the reverse direction, but keep in mind starting point is the end of inspiration so Pip=754, Ppul=Patm=760. Here the diaphragm and external intercostals relax decreasing thoracic cavity volume --> pleaural cavity shrinks to resting size, Pip becomes 756 --> lungs feel pressure gradient and shrink to resting, Ppul becomes 762 --> pressure gradient between atm and lungs causes air to move out till Patm=Ppul=760.

Forced inspiration and expiration are active processes and recruit additional muscles. In forced inspiration the sternocleidomastoids, scalenes, and pectoralis minors are recruited and these all contract to further increase the size of the thoracic cavity causing even more of a pressure gradient and therefore more air to be taken into the lungs. In forced expiration besides relaxing the diaphragm and external intercostals, the internal intercostals, and abdominal muscles are contracted. The internal intercostals pull the ribs down (opposite action of externals) and the abdominal muscles compress the abdomen pushing viscera up into the diaphragm. This causes and even greater decreases in thoracic cavity size causing even more of a pressure gradient for air to move out of the lungs.

Clinically Significant Terms and Concepts

• Pulmonary or Lung Compliance = change in volume / change in pressure
  
• Elastic Recoil
• Airway resistance
  

Compliance is the ability of your lungs to stretch and expand (increase in volume) when a change in pressure occurs (think inspiration). The more a pair of lungs can expand for a given pressure change the more compliance they have. Whereas recoil is the ability to return to resting size after expansion or stretch (think expiration).

Healthy lungs are very stretchy and can recoil easily because they have elastic connective tissue and surfactant (slippery fluid) on the alveoli. Diseases such as Mesothelioma (lung disease due to asbestos) the lungs become stiff as asbestos fibers damage the connective tissue and their compliance is reduced making it difficult to breathe. In another illness called respiratory distress syndrome, premature/preterm babies (usually less the 7months gestation) have little or no surfactant causing their alveoli to collapse and thus reducing their lung compliance. This means it is very difficult for them to inhale and expand their lungs, this can lead to exhaustion and even death.

Physiology of the Urinary System

The Urinary system consists of the kidneys which form urine and the structures that transport the urine

The Kidneys have 5 main functions:

1. Maintain plasma volume (and therefore blood pressure (BP))
2. Regulate ion and water concentration
3. acid-base balance
4. eliminate wastes, drugs, and hormones
5. endocrine - renin (BP), erythropoietin (RBC production)

Most of these functions are homeostatic

The functional unit of the kidney is the Nephron. It consists of a renal corpuscle and renal tubule. Formation of urine occurs here and involves 3 processes:

1. Glomerular filtration
2. tubular reabsorption
3. tubular secretion

Glomerular filtration is the movement of protein free plasma from blood into Bowman's capsule by bulkflow (due to a pressure gradient) across a filtration membrane. 20% of plasma in the glomerulus is filtered.

The filtration membrane consists of 3 parts:
a) fenestrated endothelium of the glomerulus
b) basement membranes
c) filtration slits between podocyte "fingers" of Bowman's Capsule

The filtrate that is produced is identical to plasma but doesn't have any large proteins. It's pH is about 7.45 and it contains water, glucose, amino acids, vitamins, ions, urea, and some small proteins (in those who consume a large protein diet)

For filtration to occur the protein free plasma had to enter Bowman's capsule using a pressure gradient (bulk flow). This gradient is caused by 4 Glomerular filtration pressures.

1. Glomerular BP = 55mmHg --favours filtration
2. Blood osmotic pressure = 30mmHg -- opposes filtration
3. Capsular hydrostatic pressure = 15 mmHg -- opposes filtration
4. Capsular osmotic pressure = 0 mmHg -- favours filtration

So, the net filtration pressure would be: (55+0) - (30+15) = 10mmHg --> favours filtration. At this average net filtration pressure we have ~ 180 L /day of filtrate produced from both kidneys. We call this the Glomerular filtration rate or GFR. This is the same as saying that the kidneys filter 125mL of blood per minute, so our entire plasma volume is filtered about 65 times every day.

If glomerular blood pressure (BP) changes so does GFR, and this change is directly proportional. This means an increase in Glomerular BP will lead to an increase in GFR

Glomerular Filtration is regulated carefully by intrinsic and extrinsic mechanisms. Intrinsic regulation or autoregulation occurs mainly at the afferent arteriole (brings blood to glomerulus to be filtered). Autoregulation is very important in normal BP ranges (when resting, even moderate exercise).

The first intrinsic method of regulating BP is myogenic stretch of the arteriole. Smooth muscle surrounding arterioles has a tendancy to contract when stretched, preventing blood pressure from reaching very high levels. In the same way, a decrease in BP will lead to less stretch of smooth muscle and a vasodilation of the afferent arteriole thus increasing GFR to normal.

The second method is called Tubuloglomerular feedback and is directed by the macula densa cells of the juxtaglomerular apparatus. These cells respond to NaCl concentration which varies with filtrate flow rate. If GFR is high, then there isn't enough time for NaCl to be reabsorbed, and the macula densa cells release a factor (most likely ATP) that causes the afferent arteriole to constrict and the flow to decrease thus lowering GFR. On the other hand, if flow rate is too slow, reabsorption of NaCl may be too much leading to afferent arteriole vasodilation and an increase of GFR to resting.

Both methods will regulate GFR to prevent it from leaving normal (homeostatic) levels.

Extrinsic regulation of GFR is via the sympathetic nervous system (SNS) which leads to vasoconstriction of the afferent and efferent arterioles. The constriction of the afferent arteriole leads to a decrease in flow entering the glomerulus, and the constriction of the efferent arteriole leads to blood backing up in the glomerulus. So since opposite actions occur, a moderate activation of the SNS leads to no change in the GFR. However, extreme stress (e.g. heavy exercise or a hemmorage) can cause GFR to decrease because so little blood will be filtered that there will be little to no back up of blood in the glomerulus when the efferent arteriole constricts.

When regulation of GFR fails, and net filtration pressure changes --> disease.
For example, blood osmotic pressure (BOP) can increase due to an increase in plasma proteins/ dehydration. So if BOP increases, then net FP will decrease, lowering GFR. Or BOP can decrease due to burns or nephrotic syndrome (glomerulus leaky and proteins get filtered) and therefore net FP increases, increasing GFR.
Also, Capsular hydrostatic pressure (CHP) can increase leading to a decrease in GFR. This may be due to a urinary tract obstruction (urine backs up) which can be caused by kidney stones (typically in ureter), inflammation, and prostate enlargement.

Tubular Reabsorption is the passive and active reabsorption of 99% of the filtrate produced. We filter 180L/day but only produce 1-1.5L/day of urine. So 99% of filtrate is reabsorbed. Na+, ions, glucose, and amino acids are actively reabsorbed (requires energy) and Cl-, water (osmosis) and urea are passively reabsorbed (no energy required). Reabsorption takes place in the:

1. proximal convoluted tubule (PCT)
2. loop of henle (LOH)
3. distal convoluted tubule (DCT)
4. Late distal convoluted tubule & collecting duct (CD)

Here are a few good links:
Quizes-
http://www.execulink.com/~ekimmel/quiz11.htm
http://kidshealth.org/kid/htbw/_bfs_USquizsource.html
http://www.lrn.org/Content/Quizzes/Qurinary.html
http://highered.mcgraw-hill.com/sites/0072907932/student_view0/chapter_19/multiple_choice_quiz.html
This site mcgrawhill includes a very good animation and a quiz
so does this one

Anatomy/physiology sites
http://www.getbodysmart.com/ap/urinarysystem/menu/menu.html
http://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm - works best with ie

animations
Counter current exchange mechanism in loop of henle - here and here