Audio Name: hhp 14d

Duration: 21 Minutes
NT111006

[00:00:00]
CLASS DISCUSSION

Hypertension
● The public health crisis of hypertension or high blood pressure.
● This is a problem of the cardiovascular system.
○ But it's also strongly affected by the renal system and especially the kidneys'
handling of sodium and water.
● Hypertension is either excessive, high systolic, or diastolic blood pressure.
● (00:40, the speaker shows a chart from the American Health Association to the class.)
○ We can see the different criteria for categorizing someone as hypertensive.
○ We should probably use the word healthy because this isn't an average.
■ This is referenced according to what we know to be healthy forthe
cardiovascular system.
■ Healthy blood pressure is considered less than 120 and less than 80.
○ Prehypertension is between 120 and 139 for systolic, or 80 and 89 for diastolic.
■ When someone is prehypertensive, we don't have a lot of associated
risks with that, but they're moving towards that hypertensive region where
we have a lot of associated risks.
○ Stage 1 Hypertension
■ Hypertension is considered between 140 and 159 systolic or 90-99
diastolic.
● It could be either one of those numbers the systolic or the diastolic
that's in that range.
○ It would mean somebody was hypertensive.
○ Stage 2 Hypertension
■ Hypertension is one 60 or higher for systolic or 100 or higher for diastolic.
■ It's considered a hypertensive crisis that requires immediate emergency
care if the systolic is greater than 180 and or the resting diastolic is
greater than 110.
● What is the problem with hypertension, what are the risks associated with this?
○ It's associated with some risks for cardiovascular disease.
○ First of all, increased blood pressure is associated with an increased risk for
vascular damage.
■ This could be something like atherosclerosis, which could lead to stroke.
■ If it leads to vascular damage within cerebral vasculature or potentially
heart attack if it leads to vascular damage within the coronary
vasculature.
■ Can also lead to vascular damage in vascular beds of the eyes, causing
vision loss or of the kidneys.
 ● Causing kidney disease or of the reproductive organs, causing
something like erectile dysfunction in males, for instance.
■ In addition to causing vascular damage due to these high pressures at
the vessel’s experience, it can also lead to chronic heart failure.
○ Chronic heart failure is due to the heart having to work too hard because it's
pumping against a very large after load.
■ It's going to adapt to pumpkin against at large afterload by actually
thickening the heart muscle.
● But in such a way that eventually that thickening muscle is going
to decrease the chamber size and as it does.
● What was sort of meant as a compensatory mechanism becomes
counterproductive and makes the heart a less effective pump?
○ And that's just sort of a downward spiral that leads to heart
failure.
● We know that with an increase in systolic blood pressure, for instance, of 20 millimeters
of mercury.
○ We roughly double our risk of vascular disease or heart failure.
● And independently of that, if we have an increase in 10millimeters of mercury of diastolic
blood pressure.
○ We're going to double our disease of the risks of that disease.
● We know that hypertension is a bad thing that we need to control.
● (4:10, the speaker shows in terms of its prevalence, roughly one-third of U.S. adults
have hypertension.)
○ 20% are unaware of this, hypertension doesn't have any outward symptoms.
○ A person doesn't necessarily know they have hypertension unless they're being
monitored, they're having their blood pressure taken regularly.
■ Many of the people who have hypertension are unaware of it, in many
cases, it's called a silent killer.
○ Now one thing to appreciate is that hypertension prevalence increases
substantially with age, and this is mostly because as we age, our arteries tend to
become stiffer due to arteriosclerosis.
■ And that stiffening leads to an increase in especially systolic blood
pressure.
○ If we're looking at young adults ages 18 to 39, we have an overall relatively low
prevalence.
○ As we go to 40 to 59, we see it increase roughly four or fivefold, and then as we
go to 60 and older, we see it double again in terms of prevalence.
■ And we have a much greater risk as we age.
○ Also, appreciate that race or ethnicity has a big impact on hypertension as well,
and specifically, the non-Hispanic black population has a substantially higher
risk of hypertension versus non-Hispanic whites, Hispanic or non-Hispanic
Asian population.
● What causes high blood pressure on order to understand that we first need to
understand the determinants of blood pressure itself?
 ○ Remember this important equation that we introduced in the cardiovascular
chapter mean arterial pressure is the product of cardiac output andTPR or total
peripheral resistance.
○ If we look first at the cardiac output, we know, of course, that that's the product
of stroke volume.
○ Heart rate's going to be controlled by your sympathetic nervous system, which of
course, speeds it up, and your parasympathetic nervous system, that'll slow it
down.
■ As well as potentially hormones like plasma epinephrine, your stroke
volume is going to be affected largely by blood volume and blood
volumes, effects on venous pressure, and venous return.
○ Of course, stroke volume is also going to be influenced by the activity of the
sympathetic, nervous to the heart by influencing the ventricular contractility or
how strongly those ventricles are going to contract.
■ Those are the factors that are going to influence cardiac output.
● The factors that will influence total peripheral resistance.
○ Include local control, these are local ways of constrictors and vasodilators.
■ Especially important as it pertains to hypertension are probably the
factors that are released by the endothelial cells.
● There's a lot of evidence that chronic hypertension can be linked
to the dysfunction of those endothelial cells.
○ In addition to those local factors, certainly, neural controls are sympathetic,
nerves being invasive, constrictors come into play.
○ As well as hormonal controls, we have our important basal constrictors,
epinephrine angiotensin to invasive frozen.
○ As well as our vasodilators of particular note, ANP or atrial natriuretic peptide.
■ The factors that are going to ultimately affect arterial radius and through
that effect, total peripheral resistance.
● We can regulate blood pressure in the short term, this is accomplished by the
baroreflex.
○ If our blood pressure goes up, that's going to increase the barrel receptor firing.
■ Which should cause a decrease in sympathetic outflow to the heart
arterials and veins.
● Which is going to decrease heart rate, decrease ventricular
contractility, decrease the resistance within those arterials and
decrease venous pressure decreasing venous return decrease in
stroke volume through the mechanism of the heart.
■ All of those things should decrease TPR and decrease cardiac output and
ideally bring more energy or pressure down.
○ We're going to increase parasympathetic outflow to the heart, which will further
slow that heart rate.
■ But remember, the baroreflex only works in the short term because those
barrel receptors will desensitize over time.
○ If we have chronically high blood pressure, the baroreceptors will desensitize and
 we'll sort of reset to a new set point at that higher pressure.
○ In the long term, we need to regulate blood pressure by regulating blood volume.
■ And this comes down to the kidneys handling of sodium and water.
● If we have high arterial pressure?
○ This is going to lead to the kidneys, increasing the loss of sodium in water.
■ There will be an increase in the glomerular filtration rate.
■ There will be a decrease in the reabsorption of sodium.
● Both through the inhibition of the renin-angiotensin-aldosterone
system, as well as through the activation of the atrial nature
Redick peptide system.
■ Along with that, we'll also have a decrease in anti-diabetic hormones as
well.
○ All of these things will cause an increase in urinary loss of sodium and water,
which will decrease plasma volume.
■ Which will decrease blood volume, which again is going to decrease
stroke volume through that starling law of the heart.
● And that should bring an arterial pressure back down.
● In the case of hypertension, something goes wrong in that mechanism that isn't doing its
job.
● What are the potential causes of hypertension?
○ It could be caused by abnormally high cardiac output or vascular resistance.
■ But in actuality, it appears that the high total peripheral resistance is
usually the culprit more than high cardiac output.
■ Appreciate that the vast majority of cases of hypertension are classified
as primary hypertension.
● This means is we don know the specific cause of hypertension up
here in this figure.
● You can see a lot of potential specific causes of hypertension, things that might cause
increasing cardiac output or an increase in vascular resistance.
● If hypertension has a specific cause, as you can see, all these potential specific causes
here, in that case, it would be called secondary hypertension.
○ Because high blood pressure is secondary to another specific cause that we can
identify.
○ But in most cases, hypertension is not necessarily secondary to any other
specific cause.
■ But rather it's probably related to a whole bunch of different factors, none
of which we can pinpoint as being the lone culprit, and thus it is termed
primary hypertension.
○ The vast majority of cases are considered primary hypertension.
● What's going to make it more likely that you will experience this disease?
○ Some of these risks are modifiable, and some of them are nonmodifiable and
important that you understand the difference between the two.
○ Non-modifiable risk factors
○ First of all, we know that gender, specifically the male gender, gives us an
 increased risk of hypertension.
■ Now that kind of normalizes a little bit once we get past the age of 60 and
women get post-menopausal, at least premenopausal women have the
protective effect of estrogen.
● And men have a greater incidence of hypertension.
○ We also know that age.
■ Is a risk factor for hypertension, as we already discussed, as we age, we
tend to have stiffening of our arteries arteriosclerosis that tends to
increase blood pressure.
○ We know that there's a strong genetic propensity for hypertension.
■ Many different genes could influence the various pathways or those
various factors.
● There's a lot of different mechanisms through which your genetic
can influence hypertension.
○ Modifiable risk factors.
○ Your modifiable risk factors are going to be things like obesity.
■ As we increase our body size, especially with body fat.
● We’re going to have a lot more vasculature to the body, which is
going to add more vascular resistance.
● More vascular resistance means higher blood pressure.
○ Lack of physical activity is also an important modifiable risk factor.
■ One, when you're physically inactive, you tend to have a lower fitness
level.
● People of a lower fitness level tend to have higher sympathetic
tone and lower parasympathetic tone.
○ That's going to contribute to hypertension.
● But also of importance here, every time you are physically active.
○ That act of being physically active immediately lowers your
blood pressure for the next 24 hours.
○ It's called post-exercise hypertension, and it's due to
local factors, largely in their effects on the arterial diameter.
○ That means if you're a regular, regularly physically active,
most days of the week, then you’re going to have this
chronic effect of a chronic decrease in resistance.
○ Stress and anxiety tend to activate the fight or flight mechanism within our body.
■ Release of catecholamines, activation of sympathetic inhibition of
parasympathetic release of stress hormones like cortisol, all of those
things are going to tend to increase blood pressure.
○ Sodium within the diet is a very important factor, and you might think that this is
largely through as we increase our sodium content that will increase our blood
volume because sodium controls our extracellular volume.
■ But it seems to be more important for some people, probably due to
genetic predisposition.
● Are especially sensitive to sodium and that it trigger an arterial or
 basal constriction.
● Excess sodium can be a problem both because of an expansion
of blood volume, but also because of excessive peripheral
resistance triggered by that sodium.
○ Then various pharmacological agents that we might take, such as alcohol,
nicotine, and caffeine, all tend to be things that increase hypertension.
● If someone is diagnosed with hypertension, we have a couple of choices in terms of how
we treat it.
● Pharmacological treatments
○ Common hypertension medications are going to target the renin-angiotensin-
aldosterone system.
○ The sympathetic nervous system than cardiac, muscle, or water retention.
○ A represents angiotensin-converting enzyme inhibitors or ACE inhibitors or
angiotensin receptor antagonists.
○ The angiotensin-converting enzyme converts angiotensin 1 to angiotensin 2.
■ Once Angiotensin 2 is produced in abundance, that's going to have two
big effects, it's going to cause basal constriction.
■ And it's also going to cause the release of aldosterone from the adrenal
cortex.
■ ACE inhibitors are going to affect blood pressure in two ways.
1. They're going to tend to cause vasodilation by inhibiting
angiotensin 2.
2. They're going to tend to decrease blood volume by inhibiting
aldosterone.
○ Category B is a beta-blocker, the ventricles of the heart have beta-adrenergic
receptors that respond to norepinephrine and anaphora, and epinephrine, and
they increase the cardiac contractility/
■ They give a stronger ventricular contraction.
■ The beta-blockers are going to act by limiting that cardiac contractility.
○ Calcium channel blockers are in effect, both smooth and cardiac muscle.
■ Calcium channel blockers will inhibit vascular, smooth muscle from
contracting and hence contribute to vessel dilation.
● They'll also inhibit cardiac muscle from contracting and hence
minimize cardiac contractility.
● Some recent evidence is indicating that calcium blockers, while they do decrease blood
pressure, might increase heart risk, higher heart attack risk, but mechanisms that are not
certainly known yet.
● The prescription and use of calcium channel blockers will probably be changing in the
immediate future because of this emerging evidence.
○ The Class D is our diabetic in a diuretic is going to, of course.
■ Lead the body to excrete more water.
■ And by excreting more water, we're going to decrease blood volume.
● Usually, the first step, if someone is diagnosed with hypertension and we want to try to
get that under control, pharmacologically if they're under 55 years of age, the first course
 of action will be an ace inhibitor.
○ If they're a person with an especially high risk of hypertension, over 55 years of
age, or African-American or Caribbean descent, in that case, they might go with
a calcium channel blocker instead.
■ But as I said, because of emerging evidence on calcium channel blockers
and the potential risk of heart attack, that might be changing soon.
○ If we're not effective in bringing that hypertension under control with step one,
then we'll try combining the ace inhibitor and the calcium blocker.
■ If that doesn't work, they'll add a diuretic to the mix.
○ If that still doesn't work, someone has resistant hypertension, then they'll either
consider further diuretic or potentially beta-blockers or an alpha-blocker, some
sort of some or antagonistic pharmacological agent.
● Non-pharmacological treatments
○ If you can be regularly active that is physically active on most days of the week,
you can decrease blood pressure by 10 points.
■ That means a combined 10 millimeters of mercury between your systolic
and diastolic.
○ If you lose five to 10 pounds of weight, that can decrease five points.
○ If you quit smoking, that can decrease five to 10 points.
○ If you limit sodium, that can decrease 2 to 8 points to perhaps if you're not that
sodium-sensitive eight perhaps if you are sodium sensitive.
■ Through this, we can accomplish a very large decrease in blood pressure.
● Every five-point decrease reduces your risk of stroke by 34 %, in your heart attack by
21%.
● We can have huge impacts on our health outcomes just for these non-pharmacological
treatments.
Audio Name: hhp 14e
Duration: 14 Minutes
NT111006

[00:00:00]
CLASS DISCUSSION

Acid-Base Balance
● Acid-base balance, which has important implications on physiological function and
health.
● The control of out of acid-base balance involves the integration of both the respiratory
system as well as the renal system.
● Extracellular fluid pH is normally around 7.4, and it must be very tightly controlled.
● Hydrogen ions have a very potent influence on arterial vasodilation, that is, they trigger
vasodilation.
○ Hydrogen ions concentration has an important influence on blood flow.
● If hydrogen ion concentration goes very low.
○ It will tend to cause vasoconstriction and limit blood flow to certain tissues,
especially the brain.
● If hydrogen ion concentrations are very high will tend to increase blood flow.
○ But could potentially drop blood pressure.
● Hydrogen ion concentration also has an important influence on tissue acceptability as
best.
○ Especially because of its interaction with other ions.
● An increase in hydrogen concentration tends to cause hypoexcitable tissue and a
decrease in hydrogen ion concentration tend to cause hyperexcitable tissue.
● Hydrogen ion concentration has an important influence on protein shape as well.
○ If we have big changes and that could potentially denature proteins or change
their shapes, which of course have dramatic impacts throughout the body.
● An extracellular patch below 7.35 is considered acidosis.
○ And you can see if we go substantially below that below 6.8 will generally cause
death.
○ But of course, we'll have some pretty severe dysfunctions even before we get to
that extreme point.
● Extracellular fluid pH above 7.45 is considered alkalosis.
○ This will generally cause death if it gets as high as 8 but will cause substantial
dysfunction.
● Causes of acidosis can either be respiratory or metabolic.
○ If they're respiratory, they're due to hypoventilation or alveolar ventilation that is
below the level necessary to sustain metabolism.
■ This could be due to drug overdose, pulmonary edema, airway
obstruction, chest trauma, or some sort of neuromuscular disease.
● But anything that causes hyperventilation is going to cause a
buildup of CO2, and that buildup of CO2 is going to cause a
 buildup of acid acidosis could also be metabolic.
● We're always generating some acid through or catabolism of proteins.
○ But other metabolic factors contribute to acidosis as well, such as diabetic
ketoacidosis.
○ If we are converting fatty acids into Akitio acids, that tends to contribute to
hydrogen ions.
○ Renal failure tends to cause acidosis.
○ As severe diarrhea because of the loss of bicarbonate from the GI system.
● No matter what the cause of acidosis, the consequences of it could be neurological
impairment, and this often comes from a change in excitability of that neurological tissue.
○ This could range anywhere from just general lethargy to coma and death.
■ Because of its effects on excitability, it can also cause cardiac
arrhythmias.
■ It also tends to cause hypertension because of the vessel dilating effect
of hydrogen ions and also tends to cause a resistance to
catecholamines.
● If acidosis is present chronically, maybe not to the level it's going to cause a lot of acute
issues.
○ It can also cause osteoporosis or loss of bone tissue, as well as kidney stones,
potentially kidney disease.
● Alkalosis can also be respiratory or metabolic.
○ If it's respiratory, it's caused by hyperventilation, perhaps due to anxiety, high
altitudes, or some other factors.
○ Metabolic could be loss of gastric juices, such as vomiting and loss of those
stomach acids or other potential metabolic causes as well.
○ The consequences of alcohol losses could be poor cerebral blood flow because
of the lack of hydrogen ions attending the cause that vasodilation.
■ That can cause anything from lethargy or stupor to coma or death.
■ This also tends to cause neuromuscular irritability because of the
hyperexcitable nature of the neuromuscular membranes.
■ This can lead to cardiac arrhythmias and death through that mechanism
as well.
● Both acidosis and alkalosis have very important health implications.
○ That's why we have to control acid-base so tightly.
● 3 separate systems to prevent large changes in hydrogen ion concentration.
1. Chemical buffers, largely by carbonate as well as non-bicarbonate buffers.
■ And these are kind of our immediate buffer to any large changes in
hydrogen ion concentration.
2. We also have effects on our respiration system that is reflective of changes in
ventilation.
■ This does a nice job of short-term regulation of acid-base balance
3. Our long-term regulation usually comes from the renal system and specifically it
is the regulation of excretion of hydrogen ions in bicarbonate.
● Chemical buffers in both the intracellular fluid and the extracellular fluid.
 ○ Can do a great job of minimizing the change in the hydrogen on a hydrogen ion
concentration for a given change in acid load.
■ But ultimately, they cannot fix a gain or loss in acid.
○ If we have again in acid, then our bicarbonate buffer within our exercise of their
fluids or our plasma proteins or the cause of our intracellular fluids, our
phosphate buffers, and our hemoglobin.
■ All of these things can buffer those increases in hydrogen ions and make
sure they don't show up in solution.
■ But ultimately, we still have to do something to get rid of that excess acid,
and the chemical buffers cannot do that.
● But they're very important for preventing large rapid changes in
the hydrogen ion concentration.
■ But to ultimately get rid of that excess acid or add more acid have in the
case of alkalosis.
● The short-term system is our respiratory system.
○ Disruption and acid-base balance cause a reflex of change in ventilation.
■ The receptors here are largely our peripheral chemoreceptors within our
arteries that sense hydrogen ion concentration.
○ If hydrogen ion concentration goes up, if we have acidosis, then the response is
going to be hyperventilation.
■ That hyperventilation will blow off excess CO2 as we build off the
excessCO2 that's going to cause a decrease in hydrogen ion
concentration.
○ The response to alkalosis will be the exact opposite of that if we have a decrease
in hydrogen ion concentration, then we will have reflexive hyperventilation.
■ We'll start to retain more carbon dioxide, and by retaining more carbon
dioxide, we will then increase our hydrogen ion concentration.
● The downside to Respiratory compensation is the fact that as we are reflexively
changing our ventilation to influence carbon dioxide and hydrogen ions.
○ We will be potentially influencing our oxygen content as well.
■ In cases of alkalosis that are going to trigger a reflex of hyperventilation,
we might see a decrease in our arterial partial pressure of oxygen.
■ But in some cases, respiratory responses or respiratory reflexes are our
only mechanism for changing acid-based disruption.
● If the acid-based disruption is caused by kidney problems.
○ If you have a kidney problem that’s causing the acid-based disruption, the
kidneys are not going to be able to compensate because they’re the cause of the
problem, in which case the respiratory system is the sole means of
compensation.
● Our main long-term regulation of acid-based disruption is the renal excretion of
hydrogen ions and bicarbonate.
○ This is the only mechanism available if the respiratory system is the cause of this
eruption.
○ If it's respiratory acidosis or alkalosis, then the renal system alone is going to
 compensate for that.
● Hydrogen ions are filtered, and they're also secreted through the active pumping of
hydrogen ions into the tubular lumen.
● Bicarbonate is also filtered and it's reabsorbed, but appreciate that its reabsorption is
secondary to hydrogen ions secretion.
○ Water and carbon dioxide can combine to form carbonic acid, which can
dissociate into hydrogen, iron, and bicarbonate.
○ Those hydrogen ions aregoing to be secreted as soon as they are produced.
■ The bicarbonate is going to be reabsorbed into our peritubular
capillaries.
● Once the hydrogen iron is secreted, it's going to combine with
filtered bicarbonate within the tubular lumen, which is going to
lead to water and carbon dioxide production in these two will
actually both be reabsorbed.
○ The net effect of pus secreting is one hydrogen ion was.
○ The reabsorption of bicarbonate, even though that
bicarbonate didn't come from the tubular lumen.
○ But the net effect is again and again of one bicarbonate in
extracellular fluid.
■ That's why we say that bicarbonate is reabsorbed, even though it's not
being actively transported across the luminal membrane or anything.
○ Generally, as we secrete more and more hydrogen ions, that's going to result in
more and more bicarbonate being reabsorbed.
● In the case of alkalosis where our extracellular fluid hydrogen ion concentration is low.
○ We're going to have a highly filtered load of bicarbonate.
○ But more importantly, we're going to have lower reabsorption of bicarbonate.
● Hydrogen ion concentrations are low, secretion of hydrogen ions will be below.
○ We will not secrete enough to absorb all of the bicarbonate insulin, that effect is
going to be the excretion of bicarbonate ions.
● If we have low hydrogen ion concentration and we excrete excess bicarbonate, that's
going to help to remedy the situation.
● In the opposite situation, we have acidosis or high extracellular fluid hydrogen ion
concentration.
○ We're going to secrete high levels of hydrogen ions.
■ Because we're secreting high levels of hydrogen ions, we're going to
reabsorb all of the bicarbonate.
● In this case, no excess by carbon that's going to be excreted.
○ Once we have reabsorbed all of the bicarbonate, we're going to continue to
secrete more hydrogen ions.
● But in this case, the hydrogen ions are going to combine two non-bicarbonate buffers
within the tubular lumen.
○ Especially phosphate, and then they're going to be excreted in the form of
phosphoric acid.
■ That is one way that we are going to excrete the hydrogen ions out of the
 body.
● The other thing that tends to happen in this case, in the case of acidosis is your tubular
epithelial cells can metabolize glutamine.
○ In the process of metabolizing glutamine, they produce one bicarbonate.
○ They produce ammonia, and then that ammonia is actively transported into the
tubular lumen and excreted as well.
● Through the process, we have a net gain of bicarbonate.
○ Once we've reabsorbed all of our bicarbonate by continuing to secrete those
hydrogen ions,
○ We are producing more bicarbonate that's getting reabsorbed into the pair of
tubular capillaries and coming into the extracellular fluid.
■ We are excreting excess hydrogen ions and so through excretion of
excess hydrogen ions in reabsorption of our bicarbonate.
● We are going to remedy that acidosis.
Audio Name: hhp 15a
Duration: 36 minutes
NT777

[00:00:43]
CLASS DISCUSSION

Digestive System
● The digestive system transfers organic nutrients, vitamins, minerals, and water from the
foods that a person’s eat to the internal environment
● The gastrointestinal tract (GI tract) to the alimentary canal is essentially a tract that is
open or continuous with the environment
● The structure will extend through the torso, through the abdomen, and ends with the
anus

○
○ The lumen of this tube is continuous with the external environment
■ Therefore, whatever is in the inside of the lumen is technically exterior to
the internal environment of the bodies
● Upon entering the internal environment, nutrient molecules will be transported to the
cells throughout the body by the circulatory system
● Important Point: after a person consume foods, the food will move to the alimentary
canal or to the GI tract
○ However, it is not until the nutrients within the food had lived in the GI tract and
enter the body tissues and the circulatory system to be distributed throughout the
body that technically, the nutrients can be used to support human function
● Prior Concepts That Understands Digestive Physiology
○ Pool Substances
■ Beginning with a particular substance, remember that the pool of the
substance is not the amount that is not available to support body function
 ■ The idea is that there are ways to increase the size of the pool, meaning
increasing the amount available to do biological work as well as ways to
decrease the amount of substances available
■ The digestive system place a role here:

●
○ This is because a person can consume the nutrients or the
molecules in the food that the person eats
■ Once they enter body tissues or the internal
environment, they can be part of the pool and the
body tissues can use these nutrients to carry out
biological activities
■ There is also a way to eliminate excesses from the body to the digestive
system
● The GI tract can also be a way to help remove excesses
substances from the pool
○ The Role of Epithelial Cells
■ Epithelial cells separate compartments

■
● The ideas in this image also apply to the gastrointestinal tract
● In the lumen, the foods that were consumed would be in the
lumen and will be separated to the digestive and absorptive
processes
● During absorption, what happen is that the nutrients will cross
through the absorption cells to enter the circulatory or lymphatic
system to be distributed throughout the body
 ○

■
● In order to move the nutrients from the lumen to the blood vessels,
there has to specific transport to facilitate this movement
○ What is the human body made of?
■ Macromolecules
● These can be used as the substrate for ATP production
■ Minerals
● These are related more to sodium, potassium, calcium, chloride,
etc.
■ Water
● This is very important because it is a large substantial contributor
to the internal environment
■
● This picture proportionalized the chemical compounds that make
up human body
○ Example
■ A large proportion of human body is made up of
water, but a person also relies on lipids, proteins,
carbohydrates, minerals, and vitamins to carry out
biological activities
● The idea here is that the nutrients can be brought into the body
through the foods that a person eats

■
● This figure reiterates 1 content that there are few key ideas that
are important to keep in mind in studying digestive physiology
 ● Macromolecules
○ These are made up of bonds that will link the different
monomers into the macromolecules
● The role of the digestive system is to take the large
macromolecules that are in the foods that were eaten and do the
reverse, breaking them down so that the smaller products of the
digestion can be more easily absorb from the lumen of the GI tract
into the cardiovascular system or the lymphatic system that will be
distributed throughout the body
● Carbohydrates
○ These are made up of sugar units
● Proteins are made up of amino acids
○ There are 20 different amino acids that can be found in the
food that a person eats
● Triglycerides are fatty acids

○
■ This schematic is the glycerol units and you can
see that there are 3 fatty acids that are bound to
the glycerol to form triglycerides
○ Looking at the product of digestion, there can be a
monoglyceride
■ There is glycerol and 1 fatty acid chain plus 2 fatty
acids
● The Structures that make up the Gastrointestinal Tract (GI Tract)
○ The gastrointestinal tract is also known as the alimentary canal
○
○ 1. Mouth
■ This is the first structure that the food will pass through
■ Foods will bring to the mouth and it will be chewed
■ As the person begins to swallow foods, the foods will move from the
mouth into the pharynx
○ 2. Pharynx
■ This is a common passageway for both food as well as air
■ As a person swallows a food, the epiglottis will be going to cover the
trachea so that the food will not go into the trachea, instead it will move
into the esophagus
○ 3. Esophagus
■ This is a long tube that will move swallowed food into the stomach
○ 4. Stomach
■ From the stomach, food will be going to move into the small intestine
○ 5. Small Intestine
■ This are made up of these structures:
 ●
■ From the small intestine, the food will be going to move into the large
intestine
○ 6. Large Intestine
■ This is named large intestine because it is a large structure and this will
lead to the anal canal
○ 7. Anus Canal
■ Any remains that will remain into the gastrointestinal tract can be
eliminated from the body to the anus
○ These primary structures that the food products will pass through as they were
processed by the digestive system
● Fact about Gastrointestinal Tract
○ This is about 30 feet long
■ There are couple of reasons for this
● 1. The gastrointestinal tract does have layers that are partially
contracted
● 2. There are surface areas in the small intestine because the
small intestine is convoluted
○ It maximize surface areas from the nutrient absorption
● Accessory Organs of Digestion
○ The accessory organs and tissues also helps in the digestion of food to release
the nutrients
■ However, few will not go into the structures, rather, the accessory organs
will produce secretions that will be added into the gastrointestinal tract
● Some of the important structures include:
 ○
○ 1. Salivary Glands
■ These are shown in yellow in the picture
■ These produce salivary that is secreted into the
mouth
○ 2. Liver
○ 3. Gallbladder
○ 4. Pancreas
■ Exocrine Portion
● An exocrine gland decrease products
through ducts into the lumen
● The exocrine pancreas will secrete digestive
enzymes into the lumen of the small
intestine
■ Endocrine
● The endocrine cells within the pancreas
produce hormones that will be released into
the blood
● Digestive System Processes
○ The GI system relies on 4 processes to turn ingested food into usable pieces,
meaning to extract the new nutrients and then to get the nutrients into the blood
for transportation to body cells
■ This is represented by this image
 ●
○ This shows the 4 main processes: Digestion, Absorption,
Secretion, and Motility

○
■ This represents the primary structures of the
gastrointestinal tract
● Food and water will enter the mouth from
the esophagus into the stomach
○ The small particles of food in the
stomach will move into the small
intestine
■ Then it will move into the
colon where the large
intestine are, and into the
rectum and eventually out to
the anus as feces
○ There can be both absorption and secretion

○
■ These arrows help to represent absorption and
secretion, and the proportion of absorption and
secretion that may take place in each organ of the
gastrointestinal tract
○ 1. Digestion
■ This refers to the breakdown of a whole food into absorbable pieces or
nutrients
■ 2 forms of digestion
● 1. Mechanical Digestion
○ This is the physical breakdown of foodstuffs
○ Example
■ Chewing a food
 ● You are breaking the food into smaller
pieces so that it can advance to the
remainder of the GI tract
● 2. Chemical Digestion
○ This is an enzymatic breakdown process
○ The enzymes can break the molecular bond to produce
smaller pieces of the particular food
● Important to note: both mechanical and chemical digestion will
occur in the entire link of the gastrointestinal tract
○ 2. Secretion
■ This is where enzymes and other chemicals released by exocrine glands
will be added to the lumen of the GI tract to aid in digestion
■ Secretion means that the digestive enzymes are secreted into the lumen
to help with the chemical breakdown of the food particles or some other
digestive functions
■ Example
● Amylase
○ They can break the molecular bond to create the
monosaccharides

■
○ 3. Absorption
■ This is the process by which digestive molecules and small nutrients will
move from the lumen of the GI tract to the epithelial cells and will enter
the blood vessels
● This is represented by the black arrows in this figure:

○
■ Important thing to note: depending on the type of the nutrients, it will be
absorbed in the blood or in the lymph
● CHO, amino acids, etc. will be absorbed into the blood
● Fats and fat-soluble vitamins will be absorbed in the lymph
○ 4. Motility
■ This refers to the advancement of food particles and nutrients along the
link of the GI tract
● This will be achieved through contractions of smooth muscle in the
GI tract
■ Primary functions
● 1. Mix the contents to aid in digestion and absorption of the
nutrients
● 2. Peristalsis
○ Moving the contents of the nutrients through GI tract from
mouth to the anus
 ○ 5. Elimination
■ This is the expulsion of the remaining materials from GI tract
■ Not all foods and nutrients are absorbed
● Example
○ Fiber
■ They remain in the GI tract at all times
■ In addition to the food that a person consumes, there are secretions that
are added to the GI tract lumen that are not reabsorbed
● All of these can be eliminated in the feces
● The digestive system is capable of substantial absorption
○ On average, people consume a liter of water a day and 500-800 grams of solids
○ People secretes more than 7 liters of fluid per day
■ Math
● This is 3 times the amount of the water that the person had
ingested
○ Of all the substances consumed, 99% are absorbed in the body
● Structure of the GI Tract Wall
○ The GI tract wall has the same basic structure from mid-esophagus through the
anus
○ 1. Mucosa
■ There are epithelial cells
● They are the absorptive cells
■ There are endocrine and exocrine cells
● The endocrine cells produce hormones that will travel in the blood
● The exocrine cells produce secretions that will be going to be
added into the lumen
● Some of these hormones are in the mucosa layer and some of
these come from other places like the liver, gallbladder, pancreas,
and the salivary glands
■ Muscularis mucosa
● This is a muscular layer located in the mucosa
○ 2. Submucosa
■ Within the submucosa, there are both blood vessels and lymphatic
vessels
■ There is also known as the submucosal plexus
● This is part of the nervous system that helps facilitate a
communication form 1 part of the GI tract to another as well as
communication between the different parts of the body
○ 3. Muscularis Externa
■ This contain muscles that can constrict and dilate;
● Circular muscle, myenteric plexus, and longitudinal muscle
○ 4. Serosa
■ This is a connective tissue layer
AudioName: hhp 15b
Duration: 32 Minutes
NT203

[00:00:00]
CLASS DISCUSSION

Digestion and Absorption of Specific Nutrients: Mouth, Esophagus, and Stomach

● Lecture Outline
○ GI Regulation
■ The coordination of events across the gastrointestinal tract
○ Mouth, Pharynx, and Esophagus
○ Stomach
○ Summary
● How do we go from the foods that we ingest to the digestion or the breakdown of these
food particles into the individual nutrients?
○ The next step following digestion is the absorption of nutrients into body tissues
● The GI system relies on four processes to get the nutrients from ingested foods into the
blood for use by the body
1. Digestion
2. Absorption
■ Absorption from the lumen of the GI tract into the blood
3. Secretions
■ Example: Digestive hormones
● These secretions will be added to the lumen to help with the
digestive processes
4. Motility
■ It is the movement of substances the came through the gastrointestinal
tract so that digestion and absorption can occur
● How these processes are regulated or coordinated in order to account for the type,
quantity, and timing of our food ingestion?
○ The big picture here is that we consume meals that vary in volume as well as
nutritional content.
○ There can be coordination across these processes to maximize nutrient
absorption

GI Regulation
● Most GI reflexes are initiated by luminal stimuli that act on either mechanoreceptors,
osmoreceptors, or chemoreceptors that are located in the walls of the gastrointestinal
tract
●
○ Different regions of the digestive tract or the elementary canal
■ Esophagus
■ Stomach
■ Small intestine
■ Large intestine
○ The idea is that there can be regulation of the digestive processes of the
processes occurring in each organ based on the contents of the lumen set the
stage for regulation versus some whole body need
○ In some cases, there can be regulation of nutrient digestion and absorption for
some nutrients based on demand within the body
○ Focus mostly on the luminal concentration of nutrients as the primary stimuli that
help to coordinate the activities of each of these digestive organs
● Examples of Luminal Stimuli
○ Distention of the GI tract wall
■ It is related to the volume of luminal contents
■ In essence, how big was the meal or the snack that we just consumed?
■ It will be detected by mechanoreceptors.
■ There's some stimulus that will be detected by a receptor that will activate
an efferent pathway to an integrating center, and the integrating center
will coordinate some sort of efferent response
● In that context, distention of the GI tract will activate
mechanoreceptors
● Mecahno receptors will coordinate or communicate with other
regions of the GI tract in order to coordinate the digestive
processes specific to how much dissension is experienced
○ Chyme Osmolarity
 ■ Chyme - it is the semi partially digested food contents mixed in with the
different secretions
○ Chyme acidity
○ Chyme concentration of specific products
■ Monosaccharides like glucose, fatty acids, peptides, and amino acids
■ Chyme composition is detected by chemoreceptors
■ Sometimes, this is the stimulus to activate reflex pathways to control GI
function
● Effectors
○ The structures of the GI tract from the esophagus through the large intestine all
have the same basic structure
■ Mucosal layer
● Epithelial cells that the lumen of the GI tract from the rest of the
tissues.
■ Submucosal layer
● It is where there are major blood and lymphatic vessels, as well as
a submucosal plexus that contributes to neural communication
■ Muscularis Externa
● It is made up of the circular layer, as well as the longitudinal
muscle layer
● There's also in myenteric plexus in this muscular external layer as
well
■ Serosa
● It is the outermost layer
●
○ The effectors that helped to coordinate GI regulation include the muscle layers in
the GI tract wall, in essence, the muscularis externa, and perhaps to a smaller
extent, the muscularis mucosa
○ There can be motor commands given to these muscular layers to either increase
motility or, in some cases, decrease motility
○ The second kind of effector relates to the exocrine glands that secrete enzymes
as well as other products like bicarbonate
■ Control of exocrine gland activity will modulate how much of a particular
digestive enzyme might be secreted into the lumen of the GI tract, for
example
 ○
■ There are neurons in the submucosal and myenteric plexus that can
coordinate with other neurons in that same plexus as well as other plexus
● This is part of the enteric nervous system or the communication of
either sensory information or motor commands from one part of
the GI tract to another
● For example, there can be communication between the small
intestine and the stomach.
■ Autonomic nervous system
● It can also relay motor commands that will be sent to the
myenteric plexus.
● There can be neural connections that also help to control the
submucosal plexus
● Neural Regulation
○ Enteric Nervous System
■ It is a local control system, meaning that it controls the activity of the GI
tract
■ Myenteric plexus
■ Submucosal plexus
■ Allows for communication from one region of the GI tract to another.
● Example: Chyme in the small intestine has an inhibitory effect on
gastric secretions, as well as gastric contractions to move more
chyme into the small intestine
■ If the majority of nutrient absorption occurs in the small intestine and
there is a lot of chyme already in the small intestine, it makes sense that
inhibitory signals can be relayed back to the stomach to slow down the
activities occurring in the stomach
● This allows chyme to maximize nutrient absorption from the small
intestine
 ■ Efferent neurons from the autonomic nervous system also contribute to
GI function
● When parasympathetic activity is high, secretory activity through
the exocrine glands is also high
● High sympathetic activity, on the other hand, tends to have the
opposite effect and has a negative effect on nutrient digestion

○
■ This is another example of a homeostatic reflex arc
■ Stimulus is located in the gastrointestinal lumen.
● Maybe this is distension or something related to chyme
composition.
■ There are receptors in the gastrointestinal tract walls that
chemoreceptors, osmoreceptors, mechanoreceptors that can keep track
of what's happening with that particular stimulus
■ Through the enteric nervous system, these receptors can communicate
via the nerve plexus in order to coordinate smooth muscle activity or
glandular secretions that will be related to helping to digest the kind that's
within the gastrointestinal lumen
● This is the local response
■ In addition, these receptors will also relay efferent information to the
central nervous system
● For example, we tend to get the sense that our stomach is full
 once we have consumed a large meal
■ The central nervous system can act as an integrating center and can
coordinate autonomic activity, and this autonomic activity can also
modulate nerve activity in the different nerve plexus that influence both
smooth muscle contractions and glandular secretions
■ Feedforward control
● The sight, smell, taste of food, as well as emotional states and
hunger, can act at the level of the central nervous system to start
to bring about changes in GI function, even in advance of food
● For example, if we are daydreaming about doughnuts, we might
begin to salivate
● Hormonal Regulation
○ Enteroendocrine cells
■ It is within the mucosal layer that is between the lumen of the
gastrointestinal tract

■
● The darker squares or rectangles represent the endocrine cells
that can't secrete hormones
● These cells sense luminal conditions and then release hormones
that enter the bloodstream and can impact function
● The hormone can enter the bloodstream and the submucosal
layer
■ Four (4) different hormones that will contribute to GI regulation
1. Gastrin
2. Cholecystokinin(CCK)
3. Secretin
4. Glucose-dependent insulinotropic peptide (GIP)
○ Gastrin
■ It is secreted by endocrine cells in the stomach
■ Gast is usually gastro, usually refers to the stomach
■ The stimuli for release include:
● Stomach distention
○ For example, we just consumed a meal.
● The quantity of peptides and amino acids in the stomach.
 ○ Relates to chyme and the chemical composition of chyme
within the stomach
● Increase in parasympathetic nervous system activity can lead to
gastrin secretion as well
■ Effects of Gastrin
● Increases hydrogen ion and enzyme secretion from the stomach
○ This is going to help with the digestion of the chyme that's
within the stomach
● Increases gastric motility or contractions of the stomach
● Stimulate colonic motility
○ Contractions of the large intestine that lead to the
evacuation of the feces that might be lingering in the large
intestine.
○ In essence, this removes feces from the large intestine so
that the large intestine is ready for the next bout of chyme
that might enter it
■ We consume foods and it's important that the particles, the individual
nutrients are digested so that they can be absorbed
■ Most stomach activity is related to the breakdown of proteins
○ CCK and Secretin
■ They are released by endocrine cells in the small intestine and they work
cooperatively
■ Stimuli for release
● It's related to the composition of chyme that enters the small
intestine.
● It is in part due to the amino acid, as well as the fatty acid
composition of chyme that will be the trigger for CCK secretion
● The hydrogen ion concentration or the pH of the chyme is going to
be a signal or a stimulus for secretin secretion
■ Effects of CCK and Secretin
● Secretin is going to be the trigger for bicarbonate ion secretion
from the pancreas, as well as some other pancreatic enzymes
○ The bicarbonate is there to help buffer the acidic kind that's
coming from the stomach
● CCK is going to be a signal for the liver to discharge bile
● CCK is also a signal to decrease gastric acid production and
motility of the stomach
■ The purpose of the small intestine is to support nutrient absorption
● There is chyme within the small intestine to slow down the
digestive activity of the stomach to allow time for the nutrients to
be absorbed before more chyme is added to the small intestine
○ GIP
■ It is secreted by endocrine cells, also in the small intestine
■ Gap right now, because we'll talk more about GFP in the next set of
 lectures that talk about glucose regulation in the blood.
■ Stimuli for GIP secretion
● The presence of carbohydrates and fat in the small intestine
■ Effects of GIP
● Coordinate lipoprotein lipase secretion from the pancreas, the
exocrine secretion.
● Also, it's going to be a stimulus for the pancreas to increase
insulin secretion to help regulate blood glucose levels in advance
of glucose absorption into the blood

Mouth, Pharynx, and Esophagus

● Digestion begins in the mouth
○ Typically, what happens is will take a bite of our food and we chew it.
■ This contributes to the mechanical digestion or the breakdown of larger
particles of a particular food into smaller pieces
○ Secrete saliva that contributes to chemical digestion
■ There are salivary glands located throughout the oral cavity, so the
presence of food in the mouth is the trigger for saliva secretion
■ Saliva
● It is made up of water, some mucus, bicarbonate ion, lysozyme,
which can help kill bacteria before we swallow the bacteria and it
enters the stomach, as well as two enzymes known as amylase
and lipase
● Amylase - is a class of enzymes that begins the digestion of
polysaccharides or carbohydrates
● Lipase - it begins the digestion of the fats or the triglycerides in
the food that we eat
● Pharynx and Esophagus
○ After we've chewed our food, the next thing we will do is swallow that bite
■ The bite is now known as a bolus because it's the food particles plus the
secretions within saliva
■ It will move into the pharynx and then from the pharynx into the
esophagus
○ The esophagus is a long tube that's made up of skeletal muscle at the top end,
which means it's under voluntary control and then smooth muscle at the lower
end
○ The chyme will move through the lower esophageal sphincter into the stomach.
■ The lower esophageal sphincter is important.
■ Sphincter muscle is a muscle that can open and close a pathway to allow
substances to move from one location and to the other.
○ The stomach produces hydrochloric acid that is very acidic.
○ Unless we're swallowing food, the lower esophageal sphincter stays closed so
that acidic chyme is not able to move back up into the esophagus and cause
damage
Stomach
● Functions of the Stomach
○ Mixes the bolus with gastric secretions in order to form chyme
○ Partially digest proteins
■ Compare this with amylase and lipase
● Amylase helps with the breakdown of carbohydrates and lipase
help with the breakdown of fats
● The stomach secretions are going to work primarily on proteins.
○ Regulate the rate of emptying of chyme into the small intestine - Gastric
emptying rate
■ The rate of entry into the small intestine is what's going to determine how
much time is available for nutrient absorption
■ A typical value for gastric emptying rate is about three miles per minute
■ It's also important to recognize that with the exception of a few
substances like water and aspirin, there's little absorption that occurs in
the stomach
■ The stomach is mostly about the digestion of proteins
● Anatomy of the Stomach
○ Reflex means the movement of chyme from the stomach back up into the
esophagus.
○ There are three other regions of the stomach
1. Fundus
a. It is the top part
2. Body of the Stomach
3. Antrum of the stomach.
○ Both the body and the Antrum can secrete mucus, as well as substances known
as pepsinogen and hydrochloric acid
○ There's also a pyloric sphincter on the opposite end of the stomach that's going
to control the movement of chyme through the pyloric sphincter into the small
intestine
○ Duodenum - it is the first region of the small intestine
■ The movement of chyme from the stomach into the duodenum is known
as the gastric emptying rate.
● Secretion
○ The stomach secretes a number of substances that play a role in digestion
○ Gastric pit
■ It spread throughout the body and the antrum of the stomach
■ It dives into the mucosal layer and there are some specialized cells that
make up the gastric pit
■ Mucus cells
● Are really good at producing mucus as well as bicarbonate
secretions
● The importance of these is that they help coat the lining of the
 stomach
● Once some of these other enzymes are secreted, the conditions
of the stomach become very acidic and very harsh
○ Therefore, the production of mucus, as well as
bicarbonate, helps to protect these epithelial cells that line
the lumen of the stomach
■ Parietal cells
● Secrete hydrochloric acid, as well as intrinsic factor
■ Chief cells
● Secrete pepsinogen
■ These epithelial cells will manufacture their secretions and then these
secretions can move through the lumen into the lumen at the stomach so
there can be hydrochloric acid, as well as pepsinogen that are now
available to interact with the chyme in the stomach
○ Hydrochloric Acid
■ We secrete a lot of hydrochloric acid on the daily basis, about two liters or
so
■ It has a very low pH
■ Hydrochloric acid helps to denature proteins

■
● The normal protein that maintains its normal three-dimensional
shape
● However, in an acidic environment that contributes to denaturation
of protein activity or proteins so that these proteins unravel
● They're still the primary sequence of amino acids, but the
unraveling process has begun
■ Hydrochloric acid helps to break the bonds that hold proteins in their
three-dimensional shape
■ Hydrochloric acid also helps to kill most bacteria that weren't killed off by
the lysozyme secreted in saliva
■ In the primary sequence of amino acids at some point, these long
polypeptides will need to be divided into shorter chains and then
eventually the amino acids will need to be released in order to maximize
amino acid absorption into the blood
■ Stimuli controlling the hydrochloric acid secretion
● Gastrin
 ○ It is a hormone secreted by the stomach in response to
stomach distention, as well as the quantity of amino acids
○ Gastric as a hormone will bind to receptors and then will
activate a second messenger system.
○ These hydrogen ion transporters sometimes known as
proton pumps, are located on the inside of the cell wall
○ In response to gastrin, these will move to the stomach
lumen side, and these transporters will be inserted into the
side to allow for hydrogen ion secretion into the lumen of
the stomach
○ Due to lumen distension and the presence of amino acid,
some peptides that has a stimulatory effect on gastric and
then gastric can lead to acid hydrochloric acid secretion
○ Hydrochloric acid secretion can be inhibited by already
acidic chyme, as well as distention amino acids, and fatty
acids in the duodenum
○ The adaptive value here is to slow down gastric or
stomach activity to allow time for nutrients to be absorbed
from the small intestine
● The second factor that can cause hydrochloric acid secretion
comes from the central nervous system.
○ There can be an increase in parasympathetic activity
○ Acetylcholine can also have the same effects to insert
these proton pumps in order to allow for hydrochloric acid
secretion into the lumen
○ Maybe this arises from the sight or smell of food, for
example
○ Pepsin
■ It is produced in chief sells
■ Chief cells secrete pepsinogen
● Pepsinogen is the inactive form of pepsin, known as Zymogen
● Pepsinogen is secreted in its inactive form and it will need to be
activated to become a fully functional enzyme
● This activation occurs secondary to low pH
● For example, under conditions in which hydrochloric acid is
secreted usually, pepsinogen is secreted as well, and then the
hydrochloric acid is able to convert pepsinogen into pepsin
■ Pepsin helps to accelerate protein digestion
● Moving from proteins into smaller peptides
● Pepsinogen can break some of the molecular bonds in order to
create these smaller peptides
■ Pepsin can also be important in breaking down ingested meat so that
there's a greater surface area for digestion
● Gastric Motility
 ○ The resting stomach has a very small volume, but through receptive relaxation
can accommodate large amounts of arriving food
■ Typically, an empty stomach can hold less than a quarter of a cup of
substances.
● However, when we are consuming a meal or snack, the stomach
wall can actually relax in order to accommodate up to six cups or
so, depending on individual size and habits
■ Mechanisms that allow for this relaxation
● It's largely due to parasympathetic activity that helps to relax
gastric smooth muscle
○ Peristalsis
■ It is a muscular contraction that helps to advance chyme through the GI
system
■ In response to milk consumption and gastric secretion, peristaltic waves
will sweep over the stomach and become stronger in the interim
● Depending again on how the volume of food within the stomach
that will coordinate the strength of these contractions.
● These contractions occur at about three per minute or so
■ The stomach is contracting, but the pyloric sphincter is closed
● This creates a situation known as retropulsion, where the chime
move forward
● Retropulsion, some of it is going to actually move back into the
Antrum or into the body of the stomach
● This helps with the mixing of chyme with the secretions.
■ Ultimately, this helps with the chemical digestion of the chyme within the
stomach
■ Effects on mixing
● It has a positive effect on mixing as well as digestion.
● The closing of the pyloric sphincter, however, will slow down
gastric emptying.
● Once there is a lack of nutrients within the small intestine, then the
pyloric sphincter will relax and there can be the addition of some
chyme from the stomach entering the small intestine
■ Peristaltic contractions advance to the pyloric sphincter and then there
can be retropulsion
● Eventually, there can be some gastric emptying of chyme into the
duodenum of the small intestine.
● Regulation
○ The gastric emptying rate is the first control point and regulation of the timing of
nutrient digestion and absorption
○ Typically, food remains in the stomach for about one to five hours following a
meal, depending on meal volume, as well as meal composition
○ The gastric emptying rate is also the primary factor that influences the rate at
which ingested substances show up in the bloodstream because it controls the
 entry of nutrients into the small intestine
○ The composition of chyme within the duodenum can have an effect to delay
gastric emptying to allow time for nutrient absorption
○ In addition, there can be some altering of sympathetic and parasympathetic
activity that can contribute to this
○ The majority of nutrient absorption will take place in the small intestine once
chyme from the stomach is able to move into the region of the GI tract
Audio Name: hhp 15c
Duration: 33 minutes
NT7191

[00:00:01]
CLASS DISCUSSION

Digestion
● The digestion of ingested foods begins in the mouth.
○ Mechanical digestion
■ Chewing of the food
○ Chemical digestion
■ The chemical digestion of carbohydrates will occur via salivary amylase
secretion.
■ The chemical digestion of fats is accomplished via lingual lipase
● Digestion then continues in the stomach
○ Mechanical digestion
■ We might chew our food while swallowing it and then move through the
esophagus and enter the stomach.
■ The stomach also has a process to contribute to mechanical digestion.
■ The stomach can contract and this contributes to peristalsis, but also the
retropulsion processes
■ That retropulsion will help with the mixing of luminal contents within the
stomach in order to help promote the chemical digestion of chyme
○ Chemical digestion
■ The main focus is on the chemical digestion of proteins through the
secretion of hydrochloric acid, as well as pepsin.
■ The chyme is going to move into the small intestine and this is where
digestion continues.

Small Intestine

● The majority of nutrient absorption will occur here

● There are three distinct segments of the small intestine.
1. Duodenum - It will receive chyme from the stomach
 2. Jejunum
3. Ileum
● These segments are specific by location, but they also have specific transporters.
○ There are specific transporters in the duodenum, jejunum, ileum that will help
with the absorption of specific nutrients in each region.

Structure of Small Intestine

● Circular folds
○ They extend to the lumen
○ They are intestinal villi
○ It increases the surface area within the small intestine.
○ There is a greater likelihood for chemical digestion to occur, as well as
absorption.
● Microvilli
○ Individual cells that make up the villus
● Brush border
○ Microvilli look like paintbrushes, that's why they’re called the brush border.
● All of these folded surfaces contribute to a tremendous amount of surface area to move
nutrients from the intestinal lumen into the epithelial cells.

Goblet Cells
● They secrete mucus
● The mucus can help coat the lining of the intestines to protect it from the acidic chyme
entering from the stomach.

Questions
● Where are the epithelial cells otherwise known as the absorptive cells?
○ These are the individual cells here that make up the villus.
● Where do absorbed nutrients go?
○ Nutrient absorption can occur across the microvilli into the epithelial cell.
○ While the nutrients can move across the absorptive cells and either enter the
villus capillaries, or the lacteal that is found within the mucosal layer on the
interior of the villus.
Accessory Organs
● Accessory organs of digestion
1. Liver
2. Gallbladder.
3. Pancreas
○ The function of all three of these accessory organs is to add secretions to the GI
tract
● These secretions will do one of two things.
1. They can enhance digestion.
2. The other kinds of secretions might be there to help protect the mucosa.
■ For example, the pancreas will secrete bicarbonate iron in order to protect
the lining of the duodenum from the harsh chyme coming from the
stomach.

Accessory Organs: Structures

● Duodenum
○ The first region of the small intestine that will receive chyme from the stomach.
● Ducts
○ There are ducts that will connect the accessory organs
○ These ducts will empty products into the lumen of the duodenum.
● Sphincter of Oddi
○ This is a sphincter that can open to allow the secretions to enter the duodenum
● Bile
○ It is produced in the liver
○ It will move through the common hepatic duct
○ It can be stored in the gallbladder
○ From here, bile can move through the common bile duct that will join up with the
pancreatic duct
○ Therefore, the secretions from the liver, as well as the pancreas, can pass
 through the sphincter of Oddi in order to enter the duodenum.

Liver

● The liver produces bile

● Bile can be stored in the gallbladder
● Eventually, the bile can be secreted into the duodenum
● Once bile is secreted, it is going to have some biological activities
● There is some capacity for bile salt reabsorption back to the liver.
● By this process, bile salts will help with the chemical digestion of fats.
○ Some of them can be taken up by the hepatic portal vein and returned to the
liver.
○ Only a little bit is lost in the feces.

Bile
● It is made up of:
○ Bicarbonate ions (largely)
○ Cholesterol
○ Phospholipids
○ Bile pigment
○ Bile salts
● Bile will travel from the liver to the gallbladder for concentration and storage.
○ Bile is produced fairly continuously through the liver and is stored within the
gallbladder.
○ It is only released from the gallbladder after we have consumed a meal.
● What is the stimulus for bile secretion from the gallbladder?
○ The stimulus for CCK secretion is the presence of fatty acids in the duodenum.
○ There are some enteroendocrine cells that are found within the mucosal layer.
○ These enteroendocrine cells, in the presence of fatty acids, will secrete CCK
○ CCK is a hormone, therefore, it will be transported in the blood.
● There are two primary effectors for CSK.
○ In the presence of CCK, the gallbladder will contract and that will allow bile to
flow into the common bile duct.
 ○ The sphincter of Oddi will relax and allow bile to then flow into the duodenum.

Pancreas

● It has both functions:

1. Endocrine function
■ Substances are produced and will travel through ducts to go to another
place.
■ The hormones are produced and these hormones will travel through the
blood.
2. Exocrine function

Exocrine Function
● Exocrine secretions are primarily digestive enzymes.
○ The pancreas will secrete several different enzymes that will help with the
chemical digestion of different nutrients.
○ The pancreas will secrete pancreatic amylase to help with the chemical digestion
of carbohydrates.
○ The pancreas will also secrete lipases to help with the chemical digestion of fats.
○ Finally, the pancreas will secrete trypsin and chymotrypsin to help with the
chemical digestion of proteins.
● The second type of exocrine secretion from the pancreas is the bicarbonate ion
○ The duodenum is receiving acidic chyme so the pancreas can secrete
bicarbonate ions to help buffer the acidic chyme coming from the stomach.
● Stimuli for pancreatic exocrine secretions
 ○ There are enteroendocrine cells that will secrete secretin into the blood
■ Secretin is going to be the chemical stimulus to the pancreas to secrete
bicarbonate into the small intestine
■ The overall function is to help neutralize intestinal acid.
○ The second stimulus for pancreatic exocrine secretions is CCK
■ The stimulus is going to be the presence of fatty acids or amino acids
within the small intestine.
■ These digestive enzymes can help with the digestion and absorption of
fats and proteins.
○ Digestive enzymes
■ Salivary and pancreatic amylases will help break down polysaccharide
into monosaccharide form and perhaps disaccharide form
■ Pepsin, trypsin, and chymotrypsin help to break proteins into peptides.
■ There are some other peptidases that can help with the chemical
digestion of these peptide fragments and ultimately the 20 different amino
acids can be ready for absorption.

Digestion & Absorption of Carbohydrates

 ● Polysaccharides
○ Pancreatic amylases can break these polysaccharides down into disaccharides
and monosaccharides.
○ In addition, there are some brush border enzymes that can help continue the
digestion into monosaccharides forms.
○ In the end, the carbohydrate monomers are fructose, glucose, and galactose.
● There are specific transport mechanisms in the duodenum that will help facilitate the
absorption of these nutrients.
○ Glucose and Galactose
■ These two monomer forms of carbohydrates are absorbed via the
secondary active transport mechanisms
■ Both of these transport mechanisms have to do with sodium.
■ That those sodium and these carbohydrate monomers can be absorbed
into the absorptive cell.
■ Sodium can be moved into the interstitial fluid and ultimately into the villus
capillaries through the sodium-potassium ATPase transporters
■ The glucose and galactose can move through a glucose transporter and
enter the villus capillaries.
○ Fructose
■ It has a different chemical structure.
■ It is going to move through a different transporter.
■ It is going to move via facilitated diffusion down its concentration gradient
into intestinal cells and through these glucose transporters to be
absorbed into intestinal capillaries.

Digestion & Absorption of Proteins

 ● Protein digestion began in the stomach and will be completed within the duodenum.
● Pancreatic proteases and peptidases will help with the chemical digestion of these
proteins into smaller peptides.
● There can also be further chemical digestion by the brush border peptidases into
individual amino acids.
● There are two different ways that small peptides and individual amino acids can be
absorbed into the intestinal cells.
1. These small peptides can utilize a secondary active transport with hydrogen ions
as the cotransporter in order to facilitate absorption.
■ Once these small peptides are within the intestinal cell, peptidases can
continue chemical digestion into the individual amino acids.
2. Individual amino acids within the lumen of the small intestine can be absorbed
via a secondary active cotransport mechanism with sodium to get those amino
acids into the intestinal cells.
■ Individual amino acids will move through amino acid transporters in order
to enter villus capillaries.
■ This is through a facilitated diffusion mechanism on the basal lateral side.

Digestion & Absorption of Fats

● The digestion and absorption of fats are primarily in the form of triglycerides
● Why?
○ Carbohydrates and proteins are water-soluble molecules.
○ Fats are insoluble in water and are lipophilic.
○ Therefore, the absorption pathways are going to be different.
● Bile
○ Bile acts as an emulsifier and it disrupts some of the forces that hold the free
fatty acids into this fat globule.
○ The bile salt will coat a portion of the fat globule and prevent it from re-
aggregating into a fat globule.
● Digestive enzymes
○ Bile
○ Pancreatic lipase
● Absorption via simple diffusion
 ○ Bile salts and phospholipids can help with the emulsification process so that we
have smaller emulsion droplets
○ These smaller emulsion droplets have a greater amount of surface area so that
bile salts and the pancreatic lipase can continue the chemical digestion until they
form structures known as micelles
○ Micelles are made up of free fatty acids and monoglycerides
○ These monoglycerides and free fatty acids are going to be able to diffuse into the
epithelial cells.
● What happens next?
○ Once these molecules are within the epithelial cells, they are going to be
processed by the smooth endoplasmic reticulum into structures known as
chylomicrons.
○ These chylomicrons are fatty acids, but they are also proteins and some other
specific structures lie cholesterol that will help improve their solubility in water.
○ They will be released via exocytosis and enter the lacteals
● Then what?

○ The lacteals are going to eventually dump into the lymphatic circulation
○ The lymphatic vessels will ultimately enter their products into the right heart.

Vitamin Absorption
● They undergo little digestion within the GI tract
● They are absorbed primarily along the length of the small intestine.
● There are two classes for vitamins.
1. Fat-soluble vitamins
■ A, D, E, & K
2. Water-soluble vitamins
■ Complex vitamins and vitamin C
● Depending on whether a particular vitamin is fat-soluble or water-soluble, that will affect
how it is absorbed
○ The fat-soluble vitamins will be absorbed by the same pathways used for fat
 absorption.
○ The vitamins B and C (water-soluble), are absorbed in the small intestine and
move through the hepatic portal circulation to the liver.
○ Vitamin B12 requires an intrinsic factor for absorption.

Mineral Absorption
● Minerals are also absorbed primarily from the small intestine, with the potential for
regulation along the GI tract.
● The primary minerals that are important for this particular course involve the salts like
sodium and potassium, but also calcium, iron, and others.

Water Absorption

● Water is absorbed from the small intestine by osmosis following the active absorption of
solutes (primarily NaCl)
○ 8000 mL of fluid ingested/secreted enters the small intestine per day
○ 1500 mL passes on to large intestine
○ Yet only 100 mL excreted in feces

Large Intestine
● This is where a lot of water absorption occurs
● Ileum empties into large intestine
1. Ascending colon
2. Transverse colon
 3. Descending colon
● The feces within the descending colon will enter the following prior to elimination
○ Sigmoid
○ Rectum
● Structure
○ It lacks circular folds and a villus structure
○ Not a lot of absorption occurs in the large intestine
● Functions
○ Stores undigested food prior to elimination
○ Continued water and salt absorption
○ Hosts gut microbiota
● Large intestinal motility is the rate-limiting step for total gut transit time
○ Typical time: 5 to 70 hours
○ The transit time is sped up by:
■ Colonic distension
■ Eating and gastric distension
○ Effect of fiber?
■ Eating a high fiber diet is associated with better health outcomes related
to several different disease conditions
■ Fiber is not absorbed into the blood 9it remains in the GI tract
■ It causes an increase in distention of the large intestine to speed up
transit time and reduces the likelihood that the carcinogenic agents are
likely able to adversely affect the epithelial cells

Summary of Whole-Gut Transit Times

Audio Name: HHP 16A
Duration: 46 Minutes
NT780

[00:00:01]
CLASS DISCUSSION

Storing and Releasing Energy: Events of The Absorptive and Postabsorptive States
● For the vast majority of human existence, 3 square meals a day have not been readily
available
○ Your body has to evolve because of it, so when there’s plenty of food available,
you can store as much of it as possible
○ Absorptive state
■ It’s 0-4 hours post-consumption or after eating

■
● It is the time when ingested nutrients are hitting the bloodstream
● 3 Main macronutrients:
○ 1. Glucose
○ 2. Triglycerides
 ○ 3. Amino acids
○ They can be absorbed from the GI tract
○ They can be used for energy, or they are going to be
synthesized large macromolecules that are used for
energy storage
● Everything you absorb is glucose
○ You can absorb other monosaccharides like galactose and
fructose, but they get to turn into glucose right away in the
liver
● Most cells prefer to use carbohydrates during the absorptive
period
○ Most of the carbohydrates are going to use by the skeletal
muscles
● The nervous system entirely uses glucose
● If you are not going to use the glucose for energy, the next thing
you can do is storage
○ 1. Glycogen
■ It’s the animal starch or the animal glucose polymer
○ 2. Glycogenesis is the process of making glycogen
■ You can store glycogen within the muscle and
within the liver
● You do have a limited storage space, the muscle can collectively
store 400 g and the liver can store about 500 g or 2,000
kilocalories of glucose within the entire body
● If you have unused glucose, and you max out your glycogen
storage then, it is going to be converted into alpha-glycerol and
fatty acids
○ They are going to make your storage form of fat or
triglycerides
○ These can happen adipose tissue and liver
● The triglycerides that are formed in the liver get packaged into
VLDLs (a low-density lipoprotein)

○
■ In the center, you can see a lot of lipids but mostly
triglycerides
 ○ To transport to the adipose cells for storage
○ The enzyme that breaks down lipoprotein triglycerides is
known as lipoprotein lipase
■ In order to store the fat within the adipose cells, you
need this enzyme
● Ingested lipid
○ Lipid is absorbed into the epithelial cells and packaged into
a lipoprotein known as chylomicrons
■ Chylomicrons are sent out to the circulation for the
delivery of the adipose tissue for storage
■ Chylomicrons are going to rely upon lipoprotein
lipase and they also need the glucose to provide
the alpha-glycerol
■ In addition to triglycerides, you can also ingest cholesterol

■
● HDL and LDL are cholesterol-rich lipoproteins
● Lipoprotein is primarily responsible for delivering cholesterol for
cells to use
● LDL is notable for its clinical significance that is having too much
LDL can be harmful to the vasculature
○ It tends to promote atherosclerosis
○ You tend to have too much LDL by having too much
triglyceride in the body
■ Protein that you ingest are primarily absorbed as amino acids
● They can be converted into proteins
○ It happens within the skeletal muscle
■ It has the greatest capacity to make and store new
proteins
● The rest of them is going to the liver
○ In the liver, they will be deaminated
○ The amine group will be converted into urea, and urea is
going to be removed from the body the kidneys
 ● Keto Acids are carbohydrates-like intermediates
○ They can be used as energy in the liver

○
○ Excess protein is primarily stored as fat
■ Regulation of events
● Metabolism during the absorptive state is dominated by the action
of insulin
○ Insulin is secreted by the beta cells of the pancreas
● The tissue that insulin will act upon includes:

○
● Insulin work:
○ It is a polar hormone and its receptor is located outside the
cell membrane

●
■ What results from the cascade of enzyme activation?
● It has an effect on glucose uptake
● Insulin increases the translocation of GLUT4 transporters
●
○ It also increases amino acid transporter in muscle cells
● It affects the enzymes
○ It will increase the activity of enzymes that control the
synthesis of things like glycogen, protein, fatty acids, and
triglycerides

○
○ Insulin decreases activity in enzymes controlling the
breakdown of the same macromolecules
○ Insulin increases the activity of enzymes controlling
glycolysis
 ■ Stimuli for insulin release:
● The major stimulus for insulin secretion is an increase in blood
glucose

●
○ As plasma glucose increases, it is detected by pancreatic
islet beta cells
○ Once they release the insulin in response to high blood
glucose, the effectors are adipocytes, muscle cells, and the
liver
■ Insulin secretion can happen in a feed-forward manner by incretins or
hormones that are released by the gut in response to the arrival of
nutrients within the gut

●
● The release of insulin is an integrated process
○ Post-absorptive state
■ More than 4 hours post-consumption
■ It can extend days to weeks
■ The GI tract is empty of nutrients going into the bloodstream
 ● Net catabolism is going on

■
■ Goal:
● Maintain euglycemia (a normal blood glucose level)
○ If you want an optimum brain function it is ideal to have a
euglycemia
● The desirable fasting blood glucose is between 65-99
■ The liver can add glucose to the blood via glycogenolysis
● It can be released into the blood for use by the various cells
■ The liver and kidneys can also make new glucose and the process is
known as gluconeogenesis
● It can use a different number of precursors
○ It can use lactate
○ You can get substrate from the glycerols
○ Amino acids can come from all the tissues especially from
the muscle
● You can get 180 g of new glucose a day
○ A big part on maintaining euglycemia even for not eating
for days or weeks
■ Glucose Sparing
● To allow the nervous system for priority use of the glucose
● Fatty acids from adipose tissue lipolysis
○ They are highly soluble in the blood that can be
transported in the blood as they bind to other proteins
○ Your nervous system cannot use fatty acids
● Ketones are produced when your liver breaks down fat
○ They are useful because they are carbohydrate-like energy
intermediates that can be used by all the cells of the body
○ They cannot use ketones that are derived from fatty acids
■ The most important hormone that opposes insulin is glucagon
 ● Glucagon also comes from pancreatic islet cells (alpha cells)
● Glucagon is assisted by other glucose-counter regulatory systems
● Glucagon is going to act upon the liver where it is going to
stimulate catabolism
○ It will break down energy sources and release them into
the blood
● Glycogenolysis
● Gluconeogenesis
● Ketone synthesis
■ The major stimulus in glucagon secretion is a decrease in plasma-
glucose

●
■ Factors that stimulate glucagon:
● Increased by plasma amino acids
○ It will stimulate insulin released
● Increased by the sympathetic nervous system
■ SNS and epinephrine has actions that help out during times of energy
need
● Stimulate glycogenolysis
○ Liver and muscle
● Acts on the adipose tissue and stimulates the breakdown of
triglycerides
■ Cortisol
● It has a permissive effect on glucagon and epinephrine
● In higher concentrations, it has an anti-inflammatory effect and
blocks insulin effects on target tissues
■ The major goal is to avoid hypoglycemia
● You do not want the blood glucose to drop below 65 mg/dL
 ●
● Pathophysiology of Diabetes Mellitus

○
○ Type I Diabetes
■ It is caused by insulin deficiency and the pancreatic beta-cells has been
destroyed by your own immune system
■ A complete absence of insulin
■ Less than 5% of diabetics
■ Onset is usually at a young age
■ Requires treatment with insulin
 ■
○ Type II Diabetes
■ It is characterized by insulin-resistance
■ The vast majority of diabetics
■ The insulin levels are elevated
■ The main consequences are similar to type I diabetes, which is high blood
glucose
○ Both types of diabetes have the similar side effect of chronic hyperglycemia
Audio name: hhp 16b
Duration: 47 Minutes
NT10192

[00:00:40]
CLASS DISCUSSION

The First Law of Thermodynamics

● It states that energy cannot be created or destroyed.
● The chemical energy stored within the bonds of the nutrients that you consume as food
can be converted to a number of different forms.
1. External Mechanical Work (Mechanical Energy)
■ It is shortening your muscles against resistance and much of your energy
goes for this.
2. Heat (Thermal Energy)
■ About 60% of your energy is lost as heat, especially in your catabolic
pathways as you break nutrients down into ATP.
3. Molecular Synthesis (Stored Chemical Energy)
■ The energy that will not do work or be converted to heat will be used for
molecular synthesis.
● Triglycerides or body fat
● Muscle tissue
● Other tissues in the body, such as nucleotides

Calorie
● It is the heat energy used to raise 1 gram of water 1°C
● It is a small unit of energy
○ Kcal = Calorie = 1000 calories = 4184 Joules (S.I. Unit)

Metabolic Rate
● It refers to the total energy expenditure per unit time (Kcal/day).
● Related Term
○ It is the total daily energy expenditure (TDEE) which is the 24-hour metabolic
rate.

Metabolic Rate and its Components

● In general, the total daily energy expenditure is the metabolic rate over 24 hours.
○ It can be broken down into 3 main components
1. Resting Metabolic Rate
● It is the largest component for most people
● It makes up 60 -70% of the daily calorie expenditure
2. Thermic Effect of Food
● It is the energy needed to digest and absorb the food that you eat.
 ● It makes up about 10%
3. Physical Activity
● It makes up about 20-30%
○ Depending upon how active you are, these percentages
can certainly change.
○ The resting metabolic rate and thermic effect of food are fairly constant from day
to day.
○ Physical activity can vary a lot, both from person to person as well as for one
person from day to day.

Resting Metabolic Rate

● It is the largest component of energy expenditure for most people.
● It is affected by a lot of different factors, such as size, gender, age, and other factors.
○ For most of these things, the common mediating factor is fat-free mass.

●
○ Resting energy expenditure rate is on the y-axis and fat-free mass in kilograms is
on the x-axis and there is a linear relationship between these two.
○ If you look at sex, men tend to have a higher metabolic rate than females.
■ It is because they have higher levels of fat-free mass per body size.
○ If look at age, as you age your resting metabolic rate goes down.
■ It is accounted for as you age, you also lose lean mass.
■ If you can age and maintain more of your lean mass, you will maintain
your resting metabolic rate quite nicely.
○ Fat-free mass accounts for most of your resting metabolic rate.
■ It accounts for about 60% of your metabolic rate, which means you have
about 40% that is unaccounted for or accounted for by other factors.
■ Other Factors of Fat-Free Mass
● Growth
● Disease or illness
● Body shape and size
● Hormonal status
○ It is the biggest impact beyond your fat-free mass
Resting Metabolic Rate: Hormonal Effect
● Thyroid Hormones
1. T3
■ It is the one that is predominantly active
2. T4
■ It is the one that is most released
■ It is often converted to T3 in its target tissue before it has its effect.
○ It is the most important determinant of resting metabolic rate for a given amount
of fat-free mass (calorigenic effect).
● Sympathetic Nervous System (SNS) and Epinephrine
○ They both work in conjunction with the thyroid hormones.
■ Thyroid hormones are permissive for epinephrine and norepinephrine.
● In many cases, the thyroid hormone effects might be through
augmenting the epinephrine and norepinephrine effects.
○ They have their independent pathways
● Tissues or Organs for Metabolic Control
○ Adipose Tissue
■ White Adipose Tissue
● It is also referred to as storage fat
■ Brown Adipose Tissue
● It is the fat that is responsible for metabolism regulation
○ Liver
○ Muscle
○ Pancreas
○ Brain
■ Those tissue/organs release are influenced by the brain but in turn, they
come back and influence the brain as well.

Mechanism of Increase in Metabolic Rate

1. Increase in ATP Use
○ The key factor here is the idea of a futile cycle
■ The body is doing things without any purpose only to increase energy
expenditure.
■ Futile Metabolic Cycles
● Glucose is broken down via glycolysis and converted glycolysis
products into glucose again via gluconeogenesis.
○ It ended up where it started off but in the process, ATP is
used and heat is released.
○ It used energy, even though it did not accomplish anything.
● Triglycerides can be broken down into fatty acids and those fatty
acids can be turned back into triglycerides.
● Sodium-potassium ATPase pumps are constantly pumping
sodium out and potassium is in.
 ●Calcium pumps are constantly pumping calcium out of the cells.
○ These are in the cell membranes, smooth endoplasmic
reticulum, and within muscle cells.
● Letting ions leak down their gradient so that they have to pump
them back uphill again.
2. Decrease ATP Production Efficiency
○ In the mitochondria, there is a lot of work to pump hydrogen ions into the
intermembrane space.
■ It is what the electron transport chain does
○ Carbohydrates, fats, and amino acids are broken down to release the energy to
pump hydrogen ions out.
■ Those hydrogen ions come down the gradient through ATP synthase and
ATP is made in the process.
○ What if you have all of the ATP that you need, but you still need to burn excess
energy?
■ You can uncouple the process of the proton pumping with the production
of ATP and is done through the uncoupling protein (proton channel).
■ Counterintuitive Process
● You put all of the energy into pumping the protons into the
intermembrane space.
● The uncoupling protein let it leak right back down to where it came
from.
■ If you do not need any more ATP, the proton gradient can not be used to
make more ATP.
● You will not burn more energy to maintain the proton gradient.

Diet-Induced Thermogenesis
● It is also known as the thermic effect of feeding
● It accounts for about 10% of the total energy expenditure during the day.
● A 10-20% increase in metabolic rate for several hours after eating.
○ It is roughly 2-4 hours after a meal
● What does this extra energy use for?
○ It takes energy to digest food and this comes from both secretions into the gut.
○ It takes energy for the motility of the gut
○ It takes energy for absorption of the food
■ Almost all of the polar molecules are tied to the active pumping of sodium
out the basal lateral side of the intestinal epithelium.
● It drives the absorption across the luminal side.
 ●
○ Carbohydrates and proteins result in more diet-induced thermogenesis.
○ Fats are absorbed into the lacteals in a passive diffusion process.
■ They do not require as much energy to digest and absorb fats as
carbohydrates and proteins.

Physical Activity
● It is the most variable from person to person, as well as day to day.
● Exercise Thermogenesis
○ The amount of energy that you get from exercise depends upon both the
intensity of that exercise and its duration.
■ For example, a Tour de France rider could easily burn 6,000 calories
during a tough stage of Tour de France.
● For most of us would be almost thrice our usual daily energy
expenditure in total.
○ Moderate Exercise
■ 5 kcal*kg-1*hr-1
■ It would noticeably affect your breathing, but you could still speak in
sentences, and easy to get those sentences out.
■ A 100 kg person can burn an extra 500 kcal during exercise
○ Vigorous Exercise
■ It is where you can not speak in sentences anymore.
● You can get one or two words out at a time.
■ 10 kcal*kg-1*hr-1
■ A 100 kg person can burn an extra 1000 kcal during exercise
● Non-Exercise Activity Thermogenesis (NEAT)
○ It is a low-intensity energy-requiring activity
■ For example, if you are standing up and working at your desk instead of
sitting.
○ It accounts for 100-800 kcal/day

Regulation of Energy Balance

●
○ The net gain of energy to the body comes in the form of food.
 ■ It is the energy intake
○ Net Loss of Energy from the Body
■ It is the 3 components of the daily energy expenditure.
○ If there is a mismatch between those net gains and net losses, there needs to be
either energy storage or removal from the storage to make up for that mismatch.
● If you intake more than you expend, you will store the excess that will be stored as fat.
● If you expend more than you intake, you need to rely upon your energy stores to make
up that difference.

Positive Energy Balance

● It is when the energy that you are expending is less than the energy content of the food
that you are consuming.
○ It will result in energy storage and weight gain.
● You can store energy as glycogen, but you only store about 500 grams of glycogen in
the body.
○ Once those glycogen stores are topped off, no more can go into that depot.
● You can also store energy as muscle protein, but in general muscle protein is dense.
○ It means to store energy as muscle protein, you need to gain a lot of weight.
● From an evolutionary standpoint, in an environment where energy was one of the
hardest things to come by, you do not want to store energy in a heavy dense way.
○ It makes you burn more energy carrying it around
○ You will only store energy as muscle proteins if your body has a specific reason
to believe it needs more muscle proteins.
■ It is because you have been doing strength training and putting your
muscles under tension.
○ If your body is not getting the signal that you need more muscle and if your
glycogen stores are full, your excess energy will be stored as fat.

Negative Energy Balance

● It is when energy expenditure exceeds energy intake and results in weight loss.
● Energy will be liberated from the body’s stores to meet the deficit.
○ It will be both taking energy out of the adipose tissue or fat stores, skeletal
muscle, organs, and tissues.

Set Point Theory of Total Body Energy Regulation

● The body has a certain ideal amount of stored energy it wants to maintain (set point).
○ To accomplish this, appetite and resting metabolic rate are adjusted.
● If your stored energy goes above the set point, you will decrease appetite and increase
your metabolic rate to bring it back.
● If we go below the set point, you will increase appetite and decrease metabolic rate to
bring it back.

Regulating Calorie Intake

● Short-Term Regulation of Food Intake (Appestat)
 ○ It controls appetite and is found within the hypothalamus.
● Satiety Signals
○ It is a signal that tells you that you are full and do not want to eat anymore.
1. Increased plasma glucose
● As glucose shows up in your blood, it tells you that you are full.
2. Increased plasma insulin
3. Increased plasma glucose
4. Increased plasma glucagon
5. Increased plasma GI hormones
● These are released when there is food in the G.I. tract
● Leptin
○ It is a hormone that comes from adipose cells
○ It is a stored energy indicator
■ As you get more fat, you get more leptin
○ It is a decreaser of hunger or increaser of satiety
● Hunger Signals
1. Decreased plasma glucose
2. Decreased plasma insulin
3. Decreased plasma glucose
4. Decreased plasma glucagon
5. Decreased plasma GI hormones
■ Ghrelin
● It increases hunger
● It comes from the stomach
● It is mostly released in response to low blood glucose and the
absence of food in the stomach.
● What screws up the appestat?
1. Increased palatability of food
■ If there are delicious things around, you want to eat them whether you
have enough energy stored in your body or not.
2. Stress
■ People use food as a sort of treatment or a remedy for too much stress.
3. Conditioned responses
■ You are eating because that is what you normally do in that situation, not
because you are hungry or you have a low energy status.
■ Examples
● Eating while watching TV
● Having something to snack on in the car

Leptin
● It is a peptide hormone.
● It is released by the adipose cells or fat cells
● It is released in proportion to the cell size
○ It is called adipokine
 ○ As the cells get bigger, they release more leptin
● It functions as negative feedback to prevent excessive fat accumulation
● It is an appetite suppressant
● It regulates energy expenditure or metabolic rate
○ Leptin makes the metabolic rate go up
● Mechanisms of Leptin that Affect Metabolic Rate
○ Leptin activates the hypothalamus-anterior pituitary-thyroid axis to increase
metabolic rate.
○ Leptin suppresses appetite and increases metabolic rate
■ It helps the ever-growing adipose cells to start moving in the other
direction and shrink back to the point of energy storage.

Set Point Theory: Implications for Weight Change

● Why is it foolhardy to think DIT, NEAT, or even exercise will be a simple solution for
losing weight?
○ When they increase the energy expenditure, it tends to decrease stored energy.
■ As soon as the stored energy decreases, leptin decreases
● It will increase appetite and decrease metabolic rate in a way to
still keep you at your set point.
○ If you are not making a specific effort to change your dietary practices, anything
that increases your energy expenditure will be offset.
■ It will be offset by an increase in food consumption to balance those
things out or staying out at a set point.
● The leptin feedback system should prevent excess weight gain, why is there so much
obesity?
○ The problem with that is those that messed up appetat
■ An environment with highly palatable food that is readily available and
has been put in your face with marketing 24 hours a day.
■ Stress
■ Conditioned responses
○ As these factors unrelated to energy storage overpower the appestat for long
enough, you get high leptin levels for long enough.
■ You will start to develop leptin resistance

Prevalence of Obesity
● Obesity is an energy dysregulation and is at epidemic levels worldwide.
 ○
■ 30% of the population are obese in the U.S. and some parts of the Middle
East.
■ You can see high levels in the 20% range through most of Europe,
Russia, Australia, etc.
● Obesity is strongly linked to early mortality and morbidity
○ Mortality means death
○ Morbidity means disease (cardiovascular disease, diabetes, high blood pressure,
cancer, etc.)

○
■ BMI
● It is the ratio of weight to height squared.
● It is not perfect because muscular people can have a big BMI but
it works nicely on a population level.
● Most people have a high BMI because they have too much fat.
● Obesity is an excessive accumulation of adipose tissue due to prolonged positive calorie
balance.
○ For a long time, you eat more than you were expending

Causes of Positive Calorie Balance: Genetics

● 2 Different Types of Obesity
1. Monogenic
■ It is obesity due to a polymorphism in a single gene that is responsible for
leptin production.
 ■ It is less than 1% of all cases of obesity are associated with monogenic
obesity.
2. Polygenic
■ There are likely dozens of different genes that are involved in a person's
likelihood to become obese.
● What is the heritability of obesity?
○ It means that what percentage of obesity can be accounted for by your genes or
what percentage of your likelihood is passed on.
○ About 50% of obesity is likely linked to genetics
● How do you know that?
○ They did things like twin studies so they look at monozygotic twins that are
identical twins with identical genes.
■ You could see a high level of similarity in obesity risk

■
○ If you looked at dizygotic twins that have the same environment but have
different genes, their degree of similarity in obesity is much lower.

■
○ You can also do adoption studies
■ People that have been adopted have obesity risks that are much more
closely linked to their birth parents than to their adopted parents.
○ More recently, one of the most powerful tools in looking at the genetic aspect of
diseases is called a Genome-Wide Association Study (GWAS).
■ You could take a look at the population of obese and non-obese.
■ You could look at which genes are associated with an increase in obesity
levels.
■ This has been done many times, and through this, they have identified
dozens of genes that are linked to obesity risk.
■ If you have some combination of these obesity-associated genes, you do
have a higher risk of becoming obese.
 ■

Cause of Positive Calorie Balance: Lifestyle

● Lifestyle factors are the things that you are you eating and how much energy are you
expending.
● Modern society creates an obesogenic environment that makes it difficult to prevent
excess adiposity.
● Components of an Obesogenic Environment
1. Ready availability of highly palatable food
2. Ready availability of high calorie or calorie-dense, but nutrient-poor food.
3. Lots of marketing of foods
4. An environment that discourages physical activity
■ It makes it easy to be sedentary and still get by.

Fat Patterning: Significance

●
● When you store fat for energy, your body's designated storage depot is the
subcutaneous adipose tissue.
○ It is the adipose tissue under the skin
○ It also gives insulation and helps maintain body temperature.
● Fat can also be stored in the visceral adipose tissue
○ It is the adipose tissue that surrounds the internal organs and lies within the
organs.
○ It is associated with a much greater risk of insulin resistance, a greater risk of
developing metabolic syndrome, and cardiovascular disease.
● Differences in Secretory Behavior
○ The subcutaneous adipose tissue secretes a lot of beneficial adipokines like
leptin or adiponectin.
○ The visceral adipose tissue tends to secrete a lot more inflammatory adipokines,
various interleukins, or tumor necrosis factors that promote inflammation.
● Difference in Anatomical Location
○ The visceral adipose tissue when it releases its substances (fatty acids or
adipokines), tends to go straight to the liver via the hepatic portal circulation.
■ The liver might deposit some of those fatty acids ectopically within those
liver cells, which can lead to dysfunction.
● Difference in Lipolysis Rates
○ The visceral adipose tissue has higher lipolysis rates.
■ Men can lose fat much more rapidly than women.
■ Men tend to store more fat viscerally which makes it a lot easier to lose
fat than women who store it subcutaneously, which has a lower lipolysis
rate.
■ Men tend to have a higher cardiovascular disease risk, especially pre-
menopause.
● It is because a higher lipolysis rate has a negative effect in terms
of disease risk.
● Visceral adipose tissue can serve as a proxy for ectopic fat deposition.
○ The more visceral fat you have means it is likely that it will end up in other places
it is not supposed to be.
■ For example, ectopically deposited within the liver cells, muscle cells,
pancreas, and in areas where it can do metabolic damage.
● The fat distribution between subcutaneous and visceral depots is dependent upon the
amount of fat, hormones, and genes.
○ The more fat you have, the more it will go into your visceral depots.
○ Women with more estrogen than men tend to deposit more fat subcutaneously.
■ For example, fat in the thighs and hips
■ Whereas men do not have as much estrogen so they tend to deposit it
more viscerally.
■ In post-menopause, estrogen levels go down to essentially zero.
● Women's fat deposition from that point on looks the same as
men's.
● The cardioprotective effect of estrogen goes away as well.
○ You can see that some people have a greater capacity to store subcutaneously
than others.
■ The more fat you can store in your thighs and hips means the less will
 end up getting deposited viscerally.
■ Some ethnic subpopulations from India and Aborigines from Australia
seem to have limited capacity to store fat subcutaneously.
● They are at high risk of obesity because they cannot store it
subcutaneously.
● It has to go into the visceral depot where it ultimately has a lot of
metabolic effects.
● Obesity is linked to insulin resistance, dyslipidemia, hypertension, and cardiovascular
disease.
○ All of these things combined in the metabolic syndrome that leads to the biggest
killer in modern society, atherosclerosis in cardiovascular disease.
Audio name: hhp 16c
Duration: 31 Minutes
NT10192

[00:00:01]
CLASS DISCUSSION

Leading Causes of Death in the U.S.

● Diseases related to vascular damage are the leading causes of death both in the U.S.
and worldwide.

●
● Atherosclerosis is the cause of the vascular damage that leads to these other things.

○
General Steps in Progression of Artherosclerosis
1. Development of Fatty Streaks
○ The endothelial damage can come from toxins such as cigarette smoke, high
blood pressure, high cholesterol, high blood glucose, etc.
■ It lets lipoproteins work their way underneath the endothelial cells into the
intima.
○ Once the lipoproteins are there, they promote an immune response.
■ They get swallowed by dendritic cells, macrophages, and other
macrophage-like cells.
■ The dendritic cell consumes the lipoprotein and it becomes a foam cell.
● It becomes large, nonfunctional, and non-mobile.
● It secretes a lot of cytokines that lead to inflammation and
activation of other cells.

○
2. Fatty Streaks to a Stable Plaque
○ The foam cells are secreting cytokines that cause an inflammatory response.
■ It is also causing a migration of vascular smooth muscle to that area.
○ The fibroblasts are secreting more extracellular matrix proteins and they are
forming a plaque.
○ The plague will encroach upon the lumen of the vessel
■ There will be an increase in the stiffness of the vessel and a decrease in
compliance.
■ There will be also an increase in blood pressure and resistance
○ The stable plaque will influence hemodynamics a little bit, but it will not cause
death.

○
 3. Unstable Plague
○ The plaque gets bigger and bigger and some of these cells began dying by
apoptosis.
■ As they die, they release their lipid contents into the center of the plaque
to form the lipid core.
■ The reason why they die is because of the inflammation and they get big
enough.
● The plaque does not become vascularized enough that the cells
are not getting enough oxygen that leads to death.
○ With death, you get a weakened plaque
■ The problem with a weak plaque is with the shear forces experienced
because of the flow of blood and it can rupture.
■ The rupture of the unstable plaque causes drastic outcomes.
● You get a clotting response that can either completely occlude a
vessel.
● Prevent blood and oxygen delivery from everything downstream of
the vessel.
● It might produce a thrombus that will dislodge and travel
downstream to another vessel that will completely occlude.

Metabolic Dysregulation
● Atherosclerosis is heavily influenced by a cluster of interrelated metabolic disturbances.
○ It is known as Metabolic Syndrome
● Criteria for Classification
1. Elevated waist circumference.
■ It will be indicative of visceral adiposity that harms several different
metabolic aspects.
2. Elevated fasting glucose
■ It is tied together with the idea of insulin resistance.
3. Elevated triglycerides
4. Reduced HDL
■ Reduced HDL and elevated triglycerides are indicative of dyslipidemia or
dysregulated lipid control.
5. Elevated blood pressure
 ○ To have metabolic syndrome, you need to have at least 3 of these criteria in
place.
■ You have a doubled risk for cardiovascular disease and early mortality.
○ If you have at least 3 of these in place and type II diabetes at the same time, you
will have a more than 5 times increased risk of cardiovascular disease.
○ Prevalence and Consequences
■ In terms of prevalence, 50% of U.S. adults have a metabolic syndrome
that has at least 3 of these criteria present.
■ If you look at people age 60 or above, it is an even higher percentage.

Glucose Dysregulation
● In 2011, nearly 26 million U.S. children and adults had diabetes,
○ The vast majority of these are type II diabetes
○ 79 million U.S. children and adults have “prediabetes”
■ Prediabetes is an early sign of insulin resistance that if not acted upon will
turn into diabetes.
● Diabetes
○ It is the leading cause of kidney failure, non-traumatic lower-limb amputations,
and new blindness.
○ It is the major cause of heart disease and stroke
○ It is the 7th leading cause of death in the U.S.

Type I Diabetes Mellitus

● It is caused by insulin deficiency arising from the destruction of your pancreatic beta
cells by an autoimmune response.
○ Pancreatic beta cells are the ones that release insulin
● It is less than 5% of diabetics
● Onset is usually at a young age, but not always.
○ It can be triggered later on in life by an infection or by some exposure to some
environmental agent.
● It requires treatment with insulin

Type II Diabetes Mellitus

● It is characterized by insulin resistance
○ It is a hyporesponsiveness disorder, the insulin is there but were not responding
to it.
● Causes
1. Down-regulation of insulin receptors
■ Once the insulin binds to its receptor, it is internalized and removed from
the membrane.
2. Stiffening of the plasma membrane
■ It is associated with obesity
● As you increase fat storage, you increase obesity
○ The plasma membrane has a lot of unsaturated lipids that get replaced by
 saturated lipids.
■ As you go from unsaturated lipids to saturated lipids, you end up
decreasing membrane fluidity that also decreases insulin sensitivity.
■ The membrane is not fluid enough to make the receptor perfectly
available to the insulin signal.
■
3. Antagonism of the nsulin signaling pathway
■ The insulin binds to the receptor and triggers a second messenger
pathway.
● The second messenger pathway can be antagonized or there are
various areas where it can be disrupted.
■ 2 Things that are Disrupted
1. Low-grade inflammation
○ You can get it from obesity
○ Visceral fat stores tend to release a lot of inflammatory
adipokines.
2. Ectopic lipid accumulation
○ Ectopic lipid deposits lead to toxic lipid by-products that
have also been shown to antagonize the insulin pathway.

Chronic Risks of Diabetes: Glucose Toxicity

● Either form of diabetes (type I or type II) are associated with chronic risks due to glucose
toxicity.
○ It is especially type II that are sensitive to this
○ For type I, you can control glucose by using external insulin.
○ The effects are largely tried to glycation and increased oxidative stress
■ Glycation is the addition of glucose non-enzymatically to other
macromolecules, such as proteins or nucleic acids.
■ Glucose concentration gets high enough and there is an increased risk for
it to bind to a protein.
● It makes the protein no longer functional which increases oxidative
stress or reactive oxygen species.
■ Oxidative stress can damage the body's tissues, such as blood vessels,
nerves, etc
● Which tissues are especially at risk?
○ Diabetes tends to be the leading cause of kidney disease because it damages
the glomerulus in the kidneys.
○ It leads to blindness because it damages the blood vessels within the retina.
○ It causes neuropathy, cardiovascular disease, damage within the liver and
muscles, and damage to the pancreas.

Type II Diabetes Mellitus: Treatment

 ● The best approach to it is making lifestyle changes
○ Changes in diet
■ Decrease in consumption of simple sugars or food that spike blood
glucose
■ Increasing fiber consumption and plant consumption in general
○ Physical activity
■ It helps with blood glucose control
○ Weight loss
■ Decrease those ectopic lipid stores and inflammation
○ Smoking cessation
■ Elimination of the toxins, which can compound the effects of the glucose
toxicity
○ Stress management
■ You get cortisol response (fight or flight response)
■ Increase blood glucose and blood lipid levels
● If lifestyle factors are not sufficient to control blood glucose, may need to use
pharmacological agents.
○ Metformin
■ It decreases liver production of glucose by gluconeogenesis
■ It also increases insulin sensitivity

Dyslipidemia
● The good cholesterol is the HDL and the bad cholesterol is the LDL.

●
○ HDL (High-Density Lipoprotein)
○ LDL (Low-Density Lipoprotein)

Lipoproteins
● LDL and HDL are not types of cholesterol, they are
○ There is only 1 type of cholesterol which is the cholesterol
○ Cholesterol like triglycerides is nonpolar that is very lowly soluble in the plasma.
■ They need to be transported within a lipoprotein.
● Lipoprotein
 ○ It has a nonpolar core that is surrounded by an amphipathic outer region.
■ The nonpolar core is made up of triglycerides and cholesterol
■ The amphipathic outer region is made up of phospholipids and
lipoproteins.
● General Makeup of Lipoproteins
○ Chylomicrons
■ It is an example of triglyceride-rich lipoproteins.
■ It transfers triglycerides from the gut to the rest of the body

■
○ Very Low-Density Lipoproteins (VLDL)
■ It transfers triglycerides from the liver to the rest of the body

■
○ Cholesterol Rich Lipoproteins
■ LDL
■ HDL
● It has apolipoprotein A

Lipoprotein Metabolism
● Lipids can enter the bloodstream as chylomicrons (gut) or VLDL (liver).
 ● The role of triglyceride-rich lipoproteins is to deliver the triglyceride to the adipose tissue
for storage.

●
○ A small number of lipoproteins carry the triglyceride to the adipose cells.
■ Through the help of lipoprotein lipase, they can deliver the triglyceride to
the adipose cells where it could be stored.
○ Once they deliver, these become smaller
■ The chylomicrons become chylomicron remnants
■ The VLDL becomes IDL (Intermediate Density Lipoproteins) and LDL.
○ The liver removes all of these once they have delivered their triglyceride and
done their job (4 hours)
○ LDL delivers cholesterol and phospholipid to all of the cells in the body.

Adverse Effect of High LDL: Atherogenesis

● A high number of LDL is produced as a consequence of high triglycerides levels.
○ It damages the endothelial cells and triggers atherosclerosis
● Oxidized LDL
○ It leads to endothelial dysfunction
■ They damage the endothelial cells making them release fewer
vasodilators and more vasoconstrictors.
○ They will activate the monocytes and lead to low-grade inflammation and greater
immune response, etc.
Lipoprotein Metabolism: Role of HDL
● HDL (apoA)
○ It is produced by the liver and intestines
○ It transfers lipids in both directions (cholesterol delivery and reverse cholesterol
transport).
○ It scavenges lipids from macrophages and extracellular depots
○ It has many other atheroprotective properties
○ It accepts triglycerides from triglyceride-rich lipoproteins
● HDL number decreases as triglycerides levels increase
○ Increased triglycerides acceptance from TG-rich lipoproteins and subsequent
transfer to triglyceride to the liver
■ It leads to small and dense HDL that lose their affinity for ApoA

Dyslipidemia: Treatments
● It can be managed by many of the same lifestyle factors that positively influence insulin
resistance and VAT.
○ Diet
○ Physical activity
○ Weight loss
○ Smoking cessation
○ Stress management
● If lifestyle factors are not sufficient, may need to use pharmacological agents.
○ Lipitor
■ It decreases the body’s production of cholesterol

Hypertension
● It is a major risk factor for cardiovascular disease
○ High blood pressure leads to the initial endothelial insult
● Obesity, insulin resistance, and dyslipidemia can cause hypertension.
Audio Name: hhp 17a
Duration: 38 Minutes
NT11705

[00:00:07]
CLASS DISCUSSION

Reproductive System
● The primary reproductive organs are known as the gonads

○ These include the ovaries and females, as well as the testes and males
● 2 primary functions of the gonads
○ Gametogenesis.
■ Gametogenesis refers to gammy or reproductive cell production from the
germ cells.
■ The germ cells are referred to as ova and females are sometimes known
as oocytes or eggs and spermatozoa or sperm in males
○ Sex hormones are otherwise known as gonadal steroids
■ These include androgens, estrogens as well as progesterone.
● The accessory reproductive organs
 ●
○ The top figure has to do with male reproductive physiology
○ The testes are the gonads
○ The function of the testes is 2 fold
1. Produce the gametes, which include sperm
2. Secrete reproductive hormones
■ For the females, there are 2 paired ovaries
■ The purpose of the ovaries is to produce oocytes as well as secrete
hormones
○ The gametes will move through a system of duct
■ The ducts are accessory reproductive organs through the gametes are
transported
■ The important ducks and males include the epididymis, the vast deferens,
which is the long tube that will loop up and around the bladder and lead
into the ejaculatory duct
■ The sperm will move into the urethra, which is the common passageway
for either urine or semen
○ Females
■ The primary duct will include the ovarian or the fallopian tubes
■ These will help transport the oocyte from the ovary into the uterus
● There are glands that will secrete substances into the ducts
○ Males
■ These glands include the seminal vesicles as well as the prostate gland
■ There are glands scattered throughout the uterus.
■ The glands will secrete substances into the women of the uterus

Gametogenesis
● Gametogenesis refers to the production of gametes
1. Germ cell proliferation via mitosis
■ Mitosis is the process by which one cell of the body will go through a
sequence of steps in order to produce 2 identical daughter cells
■ Cell Division will create the two daughter cells that are identical to the
original primordial or undifferentiated germ cell.
■ Each of the dodder cells, like all cells that go through mitosis, will contain
23 paired chromosomes
■ The overall purpose of mitosis is to create a population of germ cells to
support future mutagenesis

○
■ Mitosis creates this population of germ cells that will then differentiate into
over and spermatozoa
○ The timing of mitosis is going to differ for males and females and males.
○ Male
■ There can be differentiation into primary sperm at a site during the
embryonic period
■ There will be an increase in mitosis following puberty that will be
sustained throughout the rest of the lifespan
○ Females
■ The primary oocytes are all formed during fetal development
■ This means that a female is born with all of the oocytes she will ever have
● Epigenetic fetal programming
○ Epigenetic portion
 ■ The blueprints of DNA contains the chromosomes that are the blueprints
for all cellular activities
○ Epigenetic influences mean that there can be permanent changes in DNA as a
result of environmental factors
■ Now applied to get mutagenesis, some of these environmental factors
might happen in utero
○ Example
■ Some of the events that are associated with maternal health, well-being,
or environmental circumstances can cause epigenetic changes to the
germ cells that are being developed.
○ The essence is that in utero environment affects many aspects of physiological
function in the offspring
■ If there are environmental events that lead to a low birth weight baby, this
increases the risk for cardiovascular and metabolic disease for that
individual later on in life.
○ Gametogenesis is where germ cells develop into gametes via meiosis
■ Most cells of the body will have the deployed number of chromosomes
■ This is where for every chromosome there are two sets.
■ The sex cells should only have the haploid number or one single set of
chromosomes

○ A haploid sperm during fertilization will lead to the creation of a deployed zygote
● How do we go from the primary sperm out of sites or sites that have the deployed
number to the haploid number?
 ○ Chromosome replication
■ Primary sperm or primary oocytes, and females now assume that mitosis
has happened at an earlier step in, it's just not shown in this picture.
■ The primaries from out of sight are the primary oocytes that have the full
complement of chromosomes
○ The 1st step of meiosis is there will be chromosome replication and the formation
of sister cremated
■ There are 2o copies of each of the chromosomes, and some of these
chromosomes are in green and some are and purple
■ This is simply to denote that the chromosomes represent the maternal or
the paternal sister chromatin

● Crossing over
○ The crossing-over phase is where there can be mixing and matching
■ Crossing over and exchange of homologous chromosomes across the
 sister chromatin
■ Following crossing over the sister, chromatin is are not all green
■ There's a little bit of purple and there has been an exchange of
chromosomes
○ The crossing-over part is really important because it allows the mixing and
matching of maternal and paternal genes that contribute to genetic variation
■ There are many different examples online of siblings that look completely
different, even if they share the same genetic mother and father
■ Tremendous variation has to do with the crossing-over process

● The first melodic division

○ This is where the cell divides each daughter cell gets either the maternal or the
paternal sister committees of each chromosome
■ The green chromosomes have lined up on the same side and the purple
■ During the division, there is great variation and in the possible
combination of chromosomes that would be found in the secondaries
from out of sites
■ The end result is that from the first melodic division is the production of
both are fully functional secondary sperm out of sites.
■ They have all cellular components in females.
■ The secondary oversight receives the majority of the cytoplasm in the
organelles, and we see there is a second.
■ The polar body is non-viable and eventually, it will be degraded and
eliminated from the body
 ■ The secondary sperm out of sites and secondary oocytes still have the
deployed number of chromosomes
■ During the second biotic division, the sister cremated will divide into two
daughter cells
○ Males
■ The second biotic division will create four sperm It-It's with the haploid
number
■ The permits will continue to differentiate into mature sperm cells
■ The timing of this is continuous after puberty and specifically the timing
for the second biotic division continuous after puberty.
○ Females
■ We have our secondary oversight
■ The timing for the second biotic division is that it does not happen until
after fertilization
■ Sperm cell if that is able to penetrate the secondary oversight, then that
will trigger the second melodic division
■ That will lead to the production of a zygote with the full complement of
chromosomes and a second polar body that will contain the other half of
the chromosomes from the maternal source
 ○
○ It's where there's germ cell proliferation that creates this dramatic zone, yet a
new cornea that will lead to differentiation into the primary sperm out of sight or
primary oocytes
■ The primary oocyte will experience crossing over and the first melodic
division, this will be followed by the second biotic division that will give
rise to either force from its or one zygote and two polar bodies

Sex determination and sex differentiation

○
● The complete genetic composition of an individual is the genotype now related to sex
determination.
○ There are 23 paired chromosomes and the last set is the sex chromosomes
■ Genetic males will have the XY genotype
■ Genetic females will have an XX genotype
■ If there is a female, a biological female, the ovum from this female will
 contribute and X to the next offspring.
■ In male sperm cells, they can contribute either an X chromosome or a Y
chromosome in equal proportions.
○ Sex determination has to do with the chromosomes that are formed within the
zygote, sex differentiation is dependent on the phenotype
■ This refers to the appearance and function of individual sex differentiation
and big picture form is related to the development of the reproductive
system in the field in the fetus
■ This can lead to a male versus female phenotype.
■ The implications are that the Ducks will differentiate into the vast
difference for males versus the fallopian tubes for females.
■ The external genitalia would be more related to penile development and
males versus vagina and females
○ The genotype will determine whether the individual will have ovaries or testes the
gonads
○ The phenotype will depend upon the substances secreted by the female gonads
and especially the testes
● Embryonic development

○ This means that males and females at this stage still have identical structures
○ The Gonadal Ridge is shown in blue
■ The gonadal ridge will eventually differentiate into either testes or ovaries.
■ The gonadal ridge is also sometimes referred to as the primordial or
undifferentiated gonads
○ The Wolffian ducts
■ The Wolffian ducts architect depicted in the aqua color
○ Mullerian ducts
■ Are depicted by this purplish color
○ Pay attention to the color-coding because it's there on purpose
■ These are structures that will eventually differentiate into the fallopian
tubes and females
○
○ During the first six weeks of embryonic life, there is little differentiation
○ In genetic males,
■ The Y chromosome contains an SRY gene
■ The SRY stands for the sex-determining region of the Y chromosome
■ What happens is this X or Y gene codes for an S.R. Y protein that is
going to be the signal to lead to the development of the testes
■ SRY protein acts as a transcription factor, and what it signals is the
differentiation of the primordial gonads into fetal testes.
○ Testes are made up of two populations of cells.
■ Totally cells as well as latex cells.
■ Each of these cells will secrete chemical signals that will help with the
differentiation of the rest of the male reproductive system.

○
○ Females have two XX chromosomes.
■ They don't have the S.R. Y gene because they don't have a Y
 chromosome.
■ The primordial gonads do not receive the signal to differentiate into
testes, they will differentiate into ovaries.
■ Without testes, there will not be testosterone secretion and testosterone,
as the signal for differentiation into the male phenotype
■ In males, the SRY protein will cause differentiation into the testes.
■ The absence of the SRY protein will cause differentiation into the ovaries
○ In the presence of testes, testosterone will be secreted transformed the wolfy and
ducts that are in Aqua into the ducks of the male reproductive system
■ In females, what we see is that there is regression or degeneration of the
wealthy index because of the absence of testosterone.
○ The testes also secrete another substance that's known as an anti-malaria
hormone or AMH.
■ This is the signal for malaria uncut regression.
■ The malaria indexer and purple.
■ There's a regression of malaria and Toxar degeneration of these stocks in
males, whereas in females who don't secrete AMH.
■ Malaria ducts will differentiate into the fallopian tubes and the uterus

○ Testosterone is one of these hormones

■ Testosterone is the signal to the wolfy index to transform into the
epididymis, the vast deferens, seminal vesicles, as well as the ejaculatory
duct
■ Testosterone can be converted into DHT
○ DHT is another chemical signal.
■ It's a hormone that will cause differentiation or development of the penis,
scrotum, and prostate this is going to be the male external genitalia.
○ Sertoli cells will produce that anti-malaria hormone, and this is going to cause
regression of the malaria index.
 ■ Genetic males don't have differentiation of fallopian tubes

○ On the female side in the absence of AMH, because there are no fetal tests it will
cause differentiation of the malaria tubes into the uterus, the fallopian tubes, and
the inner vagina
■ In the absence of testosterone, there will be Wolffian ducts regression
and there will also not be DHT
○ The lack of DHT will lead to the development of the external genitalia that's more
commonly observed in females
■ The outer vagina, as well as the rest of the structures associated with the
female external genitalia.
○ Example:
■ Androgen insensitivity syndrome, formerly known as testicular
feminization
○
○ In genetic males who have testes sometimes they can experience a female
phenotype for the external genitalia
○ Thinking about physiology, how does this occur?
■ The components are all there however, there's defective androgen
receptor binding at target tissues, adding factors.
■ There's differentiation into testes, Sertoli cells, and latex cells.
■ There's the production of the anti-malaria hormone testosterone and then
testosterone can be converted into DHT
■ The difference is that the androgen receptors at effectors don't operate
correctly there's a mismatch in communication
■ The structures, the wolf and ducks don't receive the signal to differentiate
into the male reproductive system and the male external genitalia.
○ Under these circumstances, there can be a female phenotype, a female outward
appearance and the lack of the male tube structure, and a genetic male and
someone who has testes
■ The circulatory cells are working just fine, and they're producing anti-
malaria and hormones
○ The testes remain in the abdominal cavity
■ They don't descend as they should, and it's frequently not known that
someone is experiencing this syndrome until puberty and the absence of
the menstrual cycle in females
 ○
● Congenital adrenal hyperplasia
○ This can lead to visualization or masculine sanitization of an XX fetus
■ There's an increase in ACTH active secretions that are released into the
blood and is the signal to the adrenal cortex to produce hormones
■ Cortisol cholesterol will be used to form cortisol
○ For someone with congenital adrenal hyperplasia, there's an enzyme mutation
■ Cholesterol, instead of being used to form cholesterol, is actually going to
move down a different pathway and increase adrenal androgen secretion
○ Plasma levels of cortisol are low, which means that there is a signal to the
hypothalamus in the hypothalamus in response to low plasma cortisol levels is
going to continue to increase plasma active secretion
■ There would be an excess of plasma adrenal androgens available
○ With plenty of DHT available, the external genitalia will look ambiguous, meaning
it is difficult to tell whether it's male or female or look marginalized even though
it's a biological female
 ○ Cholesterol is the backbone of all steroid hormones
■ A schematic represents cholesterol
■ Cholesterol can be converted to progesterone
■ Progesterone can be converted into androgens, and then androgens can
be converted into estrogens
■ Estradiol and testosterone are related to cholesterol structurally they are
very similar to cholesterol

○
● Androgen secretion
○ Androgens are secreted by the teste
■ The adrenal cortex is in yellow, the adrenal medulla is in blue
■ The adrenal medulla is responsible for the secretion of catecholamines,
meaning epinephrine and norepinephrine.
■ The adrenal cortex, the outer layer is differentiated into different zones.
 ■ One of the zones is responsible for aldosterone secretion like adrenal
physiology
■ Cortisol and androgens are secreted by other zones in the adrenal cortex.
■ Androgens are produced from progesterone.
○ DHEA dehydroepiandrosterone is the form of androgens that are secreted by the
adrenal cortex
■ Based on the actions of five alpha-reductase that are located ROS found
in select tissues in the body.
■ DHT is a pretty potent androgen

Eestrogen and progesterone

● Progesterone can be produced within the ovaries, as well as the placenta.
○ Estrogens are produced from androgens, and this can occur in the ovaries as
well as the testes.
■ Estrogens can be secreted by the placenta
■ Estrogens are also produced in body fat if someone who is obese might
actually secrete more androgens than the average person
■ Estrogens can be manufactured from androgens in selected tissues.
○ For example
■ The skeletal system.
○ An enzyme known as aromatase can convert androgens into estrogens
■ Androgen conversion in some tissues, like the skeletal system, has a high
concentration of aromatase.
■ Nails tend to secrete a high level of testosterone
■ This testosterone is converted into estrogen that has favorable effects on
the skeleton, and that's why males tend to be taller than females
■ The primary estrogen found in the blood is estradiol
 ○
● Control of hormone secretion and the HPG axis
○ H stands for the hypothalamus is going to secrete gonadotropin-releasing
hormone that will be the signal to the anterior pituitary gland to secrete the
gonadotropin
■ The gonadotropin includes follicle-stimulating hormone as well as
luteinizing hormone
■ The gonadotropin circulates in the blood and will bind to receptors within
the gonads
■ These are signals that will control Gametogenesis, and secretion of sex
hormones
■ Luteinizing hormone is an important hormone that will help to control sex
hormone secretion

○
● Sex hormones will be released and circulate throughout the blood, and there can be
effects on the reproductive system itself and other systemic effects
 ○ The sex hormones are secreted by the ovaries and the testes in response to the
interplay between follicle-stimulating hormone alerts
○ The hormone can be secreted by the adrenal cortex
■ Under control of cortical trump and releasing hormone from the
hypothalamus and ACTH secreted by the anterior pituitary gland
○ Testosterone secretion.
■ The PGA access will be activated and the anterior pituitary gland is going
to secrete luteinizing hormone
■ Luteinizing hormone is going to be the signal to the leading cells within
the testes to secrete testosterone
○ The testosterone is going to do two things
1. It can have a local effect on the totally cells, and the purpose of the
circular cells is to generate the sperm cells
2. Testosterone can enter the circulation and bind to testosterone receptors
at peripheral tissues
■ This can lead to masculine singing masculine icing effects at the effectors
○ In females, there's a similar process but a bit different
■ With males, the hypothalamus will secrete gonadotropin-releasing
hormone that will cause both FH and LH to be secreted by the anterior
pituitary
■ For females, luteinizing hormone is going to bind to receptors on thicker
cells, and thicker cells actually secrete androgens
■ Some of these androgens are going to act locally on the granuloma cells,
and the granuloma cells will influence OH site development, and the
granuloma cells will also convert androgens into estrogen
■ The estrogen can enter the systemic circulation to affect the reproductive
system in females, as well as have effects on other tissues in the body
○ There can be secretion of some androgens based on the actions of aromatase
■ The ovaries can't secrete progesterone as well

○
● There are negative feedback loops based on the concentration of sex hormones in the
blood, and this is true both for males and females
○ Blood levels, plasma concentrations of estrogen and testosterone can influence
the HP axis activity
■ If estrogen or testosterone concentrations are high it can have an
inhibiting effect on the hypothalamic secretion of growth
■ Hormone-releasing hormone, as well as anterior pituitary secretion of
luteinizing hormone predominantly.
○ Both the ovaries and the testes will secrete one additional hormone in this
hormone is in heaven
■ In heaven feeds back to the anterior pituitary gland to primarily inhibit
follicle-stimulating hormone release
■ This is a way to control the rate at which oocytes, as well as sperm cells,
are produced

○
■ Both sexes secrete both hormones just in different concentrations
■ Different amounts of hormones are produced and secreted at different
points in the lifespan
○ Hormone production is cyclical across the monthly menstrual ovarian cycle and
menstrual cycle
■ Rather than being this smooth line, there's a tremendous cyclical variation
in hormone secretion in women
Audio Name: hhp 17b
Duration: 27 Minutes
NT11705

[00:00:34]
CLASS DISCUSSION

Reproductive systems

● The structures and functions are associated with the male reproductive system.
○ The testes are the primary reproductive organs
■ There are 2 tests, and they are located within the scrotum
○ 2 main functions
1. Gametogenesis or the production of the sex cells
2. Sex hormone production
● The testes and the primary function
1. Spermatogenesis
■ Spermatogenesis is the generation of mature sperm cells
■ This process occurs within the Semenov first tubules
■ At the Atassi in cross-section, there are several different compartments,
and within each compartment, there are a series of highly coiled tubes
■ These highly coiled tubes are the Semenov for tubules
■ If we were to extract the Semenov first tubules and uncoil them, the
combined length would be approximately 2 and a half football fields long
■ This means that there is a tremendous amount of surface area devoted to
sperm production in males
 2. Androgen secretion
■ This will be primarily in the form of testosterone

● 2 types of testeicular cells

○ Sertoli cells
■ These are the cells that line the seminar for US tubules
■ The Semenov first tubules in this figure right here and in the slower figure,
we're taking a look at a Semenov first tubule in cross-section
■ Sertoli cells are the cells that form the walls or line the walls of the
Semenov first tubules.
■ The primary function of the Sertoli cells in spermatogenesis
■ This is where sperm will develop and mature.
■ The Sertoli cell responds to follicle-stimulating hormones
■ In the case of the male reproductive system, the follicle refers to the
development of sperm.
■ The Sertoli cells respond to follicle-stimulating hormone and the follicle or
the sperm cells can develop in this location
○ Latex cells
■ The latex cells are actually populations of cells that are found in the
interstitial surrounding the seminar first tubules.
■ The primary function of the latex cells is to secrete testosterone.
■ Latex cells respond to luteinizing hormone
 ○ In males, the germ cells are known as sperm out of Konia
■ Spermatazoa will undergo the first and the second biotic division and they
will have become primary sperm out of sites followed by secondary sperm
out of sites
■ At the end of the second biotic division, the sperm cells are now known as
spermatids
○ The spermatids are still immature and not fully functional due to the actions of the
Sertoli cells within the Semenov first tubules the spermatids will continue to
differentiate to eventually form fully functional spermatozoa or sperm
■ This entire process takes about 64 days
■ About 300 million sperm are produced per day
■ This illustrates the idea that the body actually puts a whole lot of
biological energy into the production of sperm cells
■ Sperm production does not begin until puberty, but from that point on, it
can continue throughout the rest of the man's life

○
● Mature sperm structure
○ The acrosome is the tip of the headpiece that contain hydraulic enzymes that are
 important to help with the penetration of the oocyte site for fertilization
■ The rest of the headpiece contains the nucleus and the DNA it is followed
by the MIT piece that you see right here that contains mitochondria
■ And lastly, there is the flagellum are the tail
■ Once the sperm makes it into the female reproductive tract, there will be a
whipping motion of the flagellum in order to propel the sperm toward the
uterus and then through the fallopian tubes, where if a site has been
ovulated, fertilization might occur
■ The flagellum is able to move the sperm about one to four millimeters per
minute it actually takes several days in order to make it to the fallopian
tubes

● Spermatogenesis in the role of certain cells

○ The lumen of the Seminiferous tubule
■ These are the certain cells and there is a basement membrane at the
bottom here and you see that it is surrounded by smooth muscle-like
cells.
■ There are certain cells extending from the basement membrane all the
way towards the looming of the seminiferous first tubule
■ There are tight junctions in between adjacent certainly cells that make up
the blood testes barrier
○ The spermatogonia will mature and undergo mitosis between the basement
membrane and certain cells
■ Once the primary sperm out of sites are formed, they can move into the
Sertoli cells and move upwards towards the lumen as they are migrating
upwards through the search holey cells
■ They will undergo the first and second melodic division, and then they will
be released as sperm.
■ It hits into the element of the seminar’s first tubules.
● What exactly is the role of the search wholly cells with regard to this process?

○ Nutrient delivery to the developing sperm

■ They Help support them
○ Sertoli cells secrete most of the fluid that will be found within the seminar for us
tubule
○ They secrete a substance known as androgen binding protein.
■ Androgen binding protein does just what it sounds like it will bind to
testosterone
■ Once testosterone is bound to androgen binding protein within the limit of
the Semenov first tubule, it's in essence fixed there
■ And then the testosterone can have a favorable effect to help with sperm
maturation
○ Secrete current agent
■ Help with the proliferation, proliferation, and differentiation of the
spermatogonia
○ They secrete Hidden provides negative feedback to control the HPG axis
■ The hypothalamic pituitary-gonadal axis in order to regulate sperm
production.
○ Mullerian inhibiting substance or MIS is secreted from certain cells during the
fetal period
● What are some of the factors that can affect sperm development when we think about
sperm quality, really, there are two ways it can be quantified?
 ○
1. We can take a look at the sperm count, how many sperm are found in a semen
sample
■ Sperm count can be inhibited by elevated scrotal temperature, as well as
other things like antibiotic use.
2. Sperm morphology or the shape and the size
○ What are some of the factors that could lead to atypical sperm morphology?
■ It could be things like radiation-led pesticides, marijuana, excessive
alcohol, diet, and smoking
■ So many different environmental factors can affect sperm quality.
■ The quality of a man's sperm is in part dependent on the lifestyle
■ By making lifestyle choices, it is possible in some cases to improve the
quality of the sperm

The accessory reproductive structures

○
○ Spooked sperm will move into the epididymis where it can be stored for a period
of time
■ Sperm can move through the vast deferens into the ejaculatory ducts and
 eventually into the urethra for expulsion
■ The seminal vesicles and the prostate can secrete the bulk of the semen
along with the sperm that's within the semen.
■ There will be nutrients to support the sperm buffers against the acidic
environment of the vagina as chemicals to increase sperm motility and
prostaglandins

○ Erection is an increased rigidity of the penis due to vascular enlargement.

■ There's an increase in blood flow into the penis that will help with the
erection process
● 2 things have to happen in order for an erection to occur.
1. There has to be inhibition of sympathetic activity
■ Sympathetic activity and norepinephrine release can lead to
vasoconstriction if there's vasoconstriction that increases the resistance
and it can decrease blood flow into the penis, which is the opposite of
what happens during an erection
■ The first thing that has to happen is the inhibition of sympathetic activity.
2. There will be an increase in the activity of nonadrenergic non-call Nurkic
autonomic neurons, and in fact, these neurons release nitric oxide
○ Nitric oxide is a potent vasodilator.
■ Nitric oxide released within the penis will help to relax blood vessels,
decrease resistance and then favor an increase in blood flow
■ Along with the dilation of the arteries, blood can flow in
■ Because of the structure of the penis, as blood flows in, it actually
compresses the veins and it's going to prevent outflow.
○ Factors that will influence the generation of an erection.
■ It could be sensory information from the counter receptors.
■ Those inputs can influence the neural-mediated events associated with
 erection.
■ There can be information sending information from the central nervous
system that can also influence the activity of the neurons that lead to the
penis

○ The ejaculation phase is the discharge of the semen from the penis
■ It's a spinal reflex and we have to go way back to skeletal muscle in order
to reveal what a spinal reflex
■ A spinal reflex is made up of a few different components
■ Their sensory or affair and information that's relayed to the spinal cord
■ There's going to be one or more synapses within the spinal cord that's
going to lead to an efficient response back
○ With this spinal reflex, we switch from inhibition of sympathetic activity to an
increase in sympathetic activity
■ An increase in sympathetic activity is going to lead to the contraction of
the smooth muscle that surrounds the epididymis
■ The Vasja friends, the ejaculatory ducked, as well as potentially the
prostate and seminal vesicles
■ This is going to lead to sperm and glandular secretions that are going to
empty into the urethra, and this occurs during the emission phase.
■ The expulsion phase and is where there will be smooth muscle
contraction in the urethra as the skeletal muscles at the base of the penis
in order to expel the semen
○ What is male erectile dysfunction?
■ Erectile dysfunction, by definition, is an inability to achieve or sustain an
erection.
○ The next question is what are the potential causes?
■ The first causes are blood flow issues.
■ It could be cardiovascular disease, atherosclerosis, hypertension
■ It could be other chronic health conditions as well as we take a look at the
figure here that illustrates the incidence of male erectile dysfunction.
■ It could be temporary, excessive tobacco or alcohol use other drugs.
■ There can also be psychological causes such as depression, stress,
anxiety, reactions to medications
○ How do drugs for male erectile dysfunction work?
■ Smooth muscle cells that line the vasculature of the penis
■ Nitric oxide activates a second messenger system that ultimately
decreases intracellular calcium
■ Calcium is an important signaling mechanism for actin and myosin, cross-
bridge formation, and tension generation.
○ When nitric oxide is available, the effect is that there's a decrease in intracellular
calcium that's going to lead to smooth muscle relaxation in the case of the penis
erection,
■ The second messenger system gets this stuck, it can either lead to a
decrease in calcium or there is a way that it can be inhibited.
■ It can be stopped with an agent known as PDE5.
○ The drugs that help treat male erectile dysfunction inhibit the inhibitor if that
makes sense, and that allows for a greater decrease in calcium concentration
and therefore that smooth muscle relaxation
Hormonal regulation
● Male reproductive physiology.
○ The hypothalamus secretes gonadotropin releasing hormone
○ Follicle-stimulating hormone is the signal to the Stoli cells to produce more
Hariharan agents that will help stimulate spermatogenesis.
■ It also increases androgen binding production.
■ This will help increase testosterone concentration in the seminary for US
tubules
○ Testosterone can act as a Paraka agent
■ It can migrate to this or Tolly cells and also contribute to
spermatogenesis.
○ The second thing that can happen with testosterone is that it can be secreted into
the blood to act as a hormone
■ It can go to peripheral effectors and bring about many different
responses, both in reproductive organs as well as nonreproductive
organs
○ Even though gonadotropin-releasing hormone causes the release of both follicle-
stimulating hormone
■ Luteinizing hormone, we don't necessarily secrete them both in equal
concentrations.
○ The systemic responses to testosterone secretion.
■ Testosterone is a reproductive hormone it's going to have effects on male
reproductive physiology
○ The first application is to take a look at how it influences puberty.
■ Puberty is the development of the male secondary sex characteristics.
■ There can be the growth of facial, axillary, and pubic hair.
■ This is in part due to increased secretion of testosterone from the testes,
along with androgen secreted from the adrenal cortex
○ Testosterone is an anabolic agent
 ■ It can help deepen the voice by changing the structure of the larynx.
■ It can stimulate skin oil glands to secrete oil that can contribute to acne
and because of its anabolic properties
■ It can help with both muscle and bone growth that's associated with the
growth spurt of puberty
○ Testosterone can also be converted to other sex hormones
■ It can be converted to DHT in the prostate gland, and this helps to
maintain reproductive functions and specifically some of the secretions
that are added to the semen volume by the prostate
○ Testosterone can be secreted to estradiol in peripheral tissues through the
actions of aromatase
■ This happens in the brain, in the skeleton, as well as in body fat stores.
■ Some of the other systemic effects of testosterone include male pattern
baldness
■ Testosterone can be converted to estrogen in the brain, and this in males
can increase sex drive or libido
○ Testosterone can lead to muscle and skeleton development during puberty, but it
also helps continue to develop tissues into the early 20s and then sustain them
for quite a long time, several decades beyond this time point
■ The anabolic protein or anabolic processes associated with testosterone
also has a favorable effect on proteins
○ The kidneys can lead to an increase in your risk for a potent secretion.
■ EPO is the stimulus that's released from the kidneys.
■ It goes to the bones, and it's the signal to increase red blood cell
formation and subsequently the hematocrit
○ Testosterone can also act on the liver in order to increase serum proteins or
blood proteins

○ Testosterone that's in the blood can exhibit both long and short feedback to
 control or inhibit gonadotropin-releasing hormone from the hypothalamus.
■ If we reduce gonadotropin-releasing hormone output, it can also reduce
follicle-stimulating hormone and luteinizing hormone secretion
■ Testosterone has an additional preferential effect to inhibit luteinizing
hormone, specifically at the level of the anterior pituitary
○ There is some negative feedback control
■ If testosterone levels are too high it can reduce luteinizing hormone
secretion from the anterior pituitary, which would reduce the stimulus for
the latest cells to continue to secrete testosterone
○ What effect does anabolic steroid use then have on testicular function?
■ The issue with anabolic steroids is that testosterone and other androgens
are introduced artificially, so they're in the blood.
■ They can have negative or inhibitory effects on the hypothalamus in the
anterior pituitary.
■ Luteinizing hormone concentrations will drop and the testes will not
receive the signal for testosterone secretion
■ It can actually lead to testicular atrophy, even though there's plenty of
anabolic hormones or testosterone in the blood
○ Sertoli cells secrete and a hormone known as inhibition is going to feedback to
the anterior pituitary gland, and it preferentially inhibits follicle-stimulating
hormone
■ If the job of the Sertoli cell is to stimulate spermatogenesis if there's a
high amount of sperm that's available it will also increase, and this
provides information to the anterior pituitary to then decrease follicle-
stimulating hormone and reduce further spermatogenesis

○ The pattern of androgen secretion in males.

■ An increase in testosterone secretion that accompanies puberty, and it's
 maintained fairly well throughout adult life
■ Into the fourth decade following 40 or so testosterone concentrations will
begin to decline
■ it's really a very gradual decline in testosterone secretion.
○ Some of the causes for this could be deteriorating testicular function and perhaps
an inability to respond to follicle-stimulating hormone and womanizing hormone
○ What are some of the potential effects of the decrease in testosterone in older
men?
■ It's sometimes known as Andrew Pause, or it can even be menopause if
you would like
■ The potential effects are the withdrawal of testosterone, a decrease in
libido, or sex drive.
■ There can be a decrease in sperm count
○ There can be an increase in osteoporosis, meaning the loss of bone mineral
density, loss of muscle mass, loss of muscle strength, and going along with that
depression
■ The idea is that testosterone can have an effect on mood, and a reduction
in testosterone can contribute to depressive symptoms in older men
○ Example:
■ It can be difficult to deal with the facts and some of the consequences of
the aging process
Audio name: hhp 17c
Duration: 47 Minutes
NT10192

[00:00:46]
CLASS DISCUSSION

Female Reproductive Physiology

● While male gametogenesis is continuous after puberty, female gametogenesis is
cyclical.
○ Gametogenesis
■ It refers to the process by which germ cells mature
■ In females, it is oogenesis or the production of mature oocytes.
○ In females, this process occurs in a cyclical nature called the menstrual cycle.
■ It lasts on average 28 days, although anything between 23 days and 35
days is considered typical.
● Interactions between the hypothalamus, anterior pituitary gland, and the ovaries (the
HPG axis) will help coordinate
○ Cyclical changes in the ovaries
■ These changes are referred to as the ovarian cycle.
■ The gonads have 2 main functions
1. Gametogenesis
2. Hormone secretion
○ Estrogen
○ Progesterone
○ Testosterone
○ Inhibin
○ Cyclical changes in the uterus
■ It arises from changes in hormone secretion coming from the ovaries.
■ These processes are included within the menstrual cycle.
■ The changes that occur in the ovarian cycle and menstrual cycle are to
promote the fertilization of oocytes.
● It is also to provide an in utero environment that favors zygote
implantation in pregnancy.
Female Reproductive Tract

●
1. Fallopian Tubes/Ovary Tubes/Oviducts
■ It will lead from the ovaries to the uterus
2. Uterus
■ If fertilization occurs, the zygote can implant in the walls of the uterus.
● It will be an environment that will favor the development of a
pregnancy.
■ Endometrium
● It is an epithelial cell that lines the uterus
■ Myometrium (Myo refers to muscle)
● It is the deeper layer
● It is a region of smooth muscle that makes up the uterus.
3. Cervix
4. Vagina

Ovarian Functions
1. Oogenesis
○ It is the production of the gametes during the fetal period.
○ The primordial germ cells or the gametes will differentiate into primary oocytes.
2. Maturation of oocytes following puberty
3. Expulsion of mature oocytes from the ovary
○ This process is known as ovulation
4. Sex steroid hormones secretion
○ Estrogen
○ Progesterone
○ Testosterone
○ Inhibin
Oogenesis
● It is the production of female gametes
● Oogonia proliferate via mitosis and differentiate into primary oocytes during fetal life.
○ In males, the immature form of germ cells is called spermatogonia.
○ About 2-4 million primary oocytes will be available at birth.
● First meiotic division begins in utero but is arrested until ovulation.

●
● The first meiotic division will be completed just before ovulation
○ One daughter cell gets all of the cytoplasms
■ It is a viable cell
■ It is the secondary oocyte
○ It also leads to the creation of the first polar body
● If fertilization occurs, it will lead to the second meiotic division.
○ One of the daughter cells will receive the majority of the cytoplasm
■ It will be now referred to as a zygote
○ There is also the creation of the second polar body
○ The zygote will travel to the uterus and if the conditions are right it can implant in
the uterine wall.
● Oocyte maturation and ovulation begin at puberty and end at menopause.
○ Out of the 2-4 million oocytes that are generated during the fetal period, about
400 eggs will be ovulated throughout a woman's life.
○ The maturation of 1 primary spermatocyte leads to the formation of 4 sperm.
■ However, each oogonium only produces 1 fully mature ovum.
Ovarian Cycle
● It is a series of events associated with the maturation and the release of an egg.
1. Follicular Phase
○ It lasts approximately days 1-14 of the menstrual cycle
○ It is when a single mature follicle and secondary oocyte develop and is released.

○
2. Luteal Phase
○ It lasts from approximately days 15-28
○ This is the time period from ovulation until the degeneration of the corpus luteum.

Follicular Phase
● Oocytes exist in follicles
○ The primary oocyte is sitting in a primordial follicle
■ Primary oocytes is surrounded by a single layer of cells called granulosa
cells.
■ The granulosa cells help to support the developing oocyte and will
secrete estrogen, inhibin, and small quantities of progesterone.

○
● Some of the primordial follicles will develop into primary follicles.
○ The oocyte grows and becomes larger
○ There is a proliferation of granulosa cells and there can be multiple layers.
○ As you increase the number of granulosa cells, there will be an increase in
estrogen concentration in the blood.
○ There will be a development of a zona pellucida
■ It is an area that provides a little bit of compartmentalization between the
oocyte and the granulosa cells.
■ It enhances the sperm binding to the surface of the oocyte to favor
fertilization.
● Development of Antral Follicles
○ It is composed of a primary oocyte, multiple layers of granulosa cells, zona
pellucida, theca cells, and antrum.
■ Theca Cells
● They secrete androgens and a little bit of progesterone.
● The androgens that are produced in the theca cells can diffuse to
the granulosa cells and be converted to estrogen.
■ Aromatase
● It is an enzyme that facilitates the conversion of androgens into
estrogens.
● Granulosa cells have very high concentrations of aromatase that
is why they can manufacture estrogen that can be secreted.
■ Antrum
● It is a fluid-filled cavity
 ○
● At the start of each menstrual cycle, 10-25 of the antral follicles will begin to mature.
○ After about one week of development, all but one of the follicles will undergo
atresia (apoptosis or programmed cell death)
○ The remaining dominant follicle (Graafian follicle) will bring the oocyte to
maturation and release it.
○ The primary oocyte will undergo the first meiotic division and becomes the
secondary oocyte.

Ovulation
● Ovulation occurs around day 14 of the menstrual cycle.

○
■ The oocyte is being expelled from the ovary and it will enter the fallopian
tube and migrate towards the uterus.
● Ovulation is triggered by the surge of the luteinizing hormone
○ It will cause the dominant follicle to fuse with the ovarian wall
○ It will secrete enzymes that will help with digestion
■ The oocyte can be released from the ovary.
○ The secondary oocyte along with the granulosa cells and the zona pellucida cells
will be released and enter the fallopian tube.
 ● The 1st day of the menstrual cycle is the 1st day of bleeding and is considered as day 1.
○ Between days 1-7, multiple follicles will develop
○ Around day 7 or so, one of the follicles will become the dominant one.
○ Over the next week, the dominant follicle mature and it will be the one released
from the ovary.

Luteal Phase: Corpus Luteum

● Following ovulation, the remaining follicular cells are transformed into the corpus luteum.
○ Corpus means body and luteum refer to a yellow color.
○ The corpus lute will be converted into an endocrine structure that lasts for about
10-14 days if pregnancy does not occur.
■ If pregnancy does happen to occur, the placenta is going to secrete
hormones that will support the corpus luteum for a period of time.
○ One of the functions of the corpus luteum is to secrete hormones.
■ It will secrete estrogen, progesterone, and inhibin.

HPG Axis

●
○ The hypothalamus will secrete GnRH that acts on the anterior pituitary gland.
○ The anterior pituitary gland triggers the secretion of FSH and LH.
○ In females, the luteinizing hormone will cause actions in the theca cells.
■ Theca cells express luteinizing hormone receptors.
● Estrogen is secreted from the granulosa cells.
○ Androgens will first be produced in the theca cells and they will migrate to the
granulosa cells.
■ The granulosa cells will convert them to estrogen to be secreted into the
blood.
○ The corpus luteum is another source of estrogen secretion.
 ● Progesterone in small amounts can be secreted by the granulosa cells and theca cells.
○ However, the corpus luteum will secrete much greater quantities of progesterone.
● Inhibin is secreted from the granulosa cells and corpus luteum.

Comparison of HPG Axis Between Males and Females

● In males, the luteinizing hormone is acted upon the Leydig cells to secrete androgens
and testosterone.
● In females, the luteinizing hormone will act on the Theca cells to secrete androgens.
● In males, the follicle-stimulating hormone acts on the Sertoli cells.
● In females, the granuloma cells will influence the oocyte development
○ The granulosa cells will secrete inhibin.

Negative Feedback Inhibition

● Estrogen can feedback to both the hypothalamus to inhibit secretion of gonadotropin-
releasing hormone.
○ It can also feedback to inhibit luteinizing hormone secretion from the anterior
pituitary gland.
○ Luteinizing hormone is the stimulus for androgen secretion that will subsequently
be converted to estrogen.
■ High concentrations of estrogen should feedback and inhibit luteinizing
hormone secretion.
● Granuloma cells produce inhibin
○ Inhibin will feedback and inhibit follicle-stimulating hormones.

General Pattern of Hormone Secretion

● Luteinizing Hormone (LH)
○ At the beginning of the menstrual phase, it is quite low
○ There will be a small increase during the follicular phase
○ LH concentrations stay fairly consistent
○ Before ovulation, there will be a major spike in LH secretion
○ LH concentrations will rapidly decline at first and then slowly decline through the
rest of the luteal phase.

○
 ● Follicle-Stimulating Hormone (FSH)
○ Very low at the beginning of the menstrual cycle
○ There will be small increases during the first phase of the follicular phase
○ FSH will decrease
○ Before ovulation, there will be a spike in FSH
○ There will be a rapid return to a low level and then concentrations will slowly
decline throughout the luteal phase.
● Estrogen
○ Estrogen concentrations tend to stay low during the first part of the follicular
phase.
○ There is a big increase in estrogen, and in fact, estrogen reaches its highest
levels just before ovulation.
○ Following ovulation, estrogen concentrations will decline and then it will be
followed by a secondary increase in estrogen concentrations.
■ However, the peak values during the luteal phase will not reach the same
values as during the follicular phase.

○
● Progesterone
○ Progesterone concentrations stay fairly low during the majority of the follicular
phase.
○ They increase slightly just before ovulation
○ During the luteal phase, progesterone concentrations become very high.
○ At the end of the menstrual cycle, there is a precipitous drop in both estrogen
and progesterone.
■ It has effects to trigger menstruation.

Early Follicular Phase

● Days ~1-7
○ Luteinizing hormone will stimulate theca cell proliferation and androgen
production.
■ Androgens will be the precursors for estrogen secretion from the
granulosa cells.
○ The increase in the follicle-stimulating hormone will signal the granulosa cells to
convert androgens to estrogens and also to nourish the developing follicle.
● Why are plasma concentrations of estrogen and progesterone low during the early
 follicular phase?
○ Estrogen secretion is going to be relatively low until the granulosa cells have
enough mass to secrete more estrogen.
● What is the split in follicle-stimulating hormone triggering?
○ It is triggering the development of the follicle during the middle follicular phase at
roughly day 7or so.
■ Due to the development of the follicle and the increase in the granulosa
cells, there will be a gradual increase in progesterone secretion.

Middle Follicular Phase

● Rising estrogen levels will inhibit the secretion (but not the production) of luteinizing
hormone and follicle-stimulating hormone.
○ These are under negative feedback control
○ The anterior pituitary is still manufacturing luteinizing hormone and follicle-
stimulating hormone, but it is not releasing these hormones into the blood.
● The granulosa cells will secrete inhibin
○ Inhibin will inhibit follicle stimulating hormone.
● The decrease in follicle-stimulating hormone leads to atresia or the dying off of the
developing follicles.
○ The dominant follicle survives because it is more sensitive to the follicle-
stimulating hormone.
■ It also expresses and responds to the luteinizing hormone
○ The process of why the dominant follicle is selected to be the dominant follicle is
not well understood.
● The dominant follicle during the second half of the follicular phase begins producing
greater quantities of estrogen.
○ Estrogen concentrations are going to spike in the blood.

Late Follicular Phase

● Once a threshold level of plasma estrogen concentration is reached, the feedback
control on the anterior pituitary gland switches from negative to positive.
○ Once estrogen levels spike, it will be a positive feedback effect.
■ It will trigger the spike in both luteinizing hormone secretion and follicle-
stimulating hormone secretion from the anterior pituitary gland.
● Estrogen-mediated LH surge induces the completion of the 1st meiotic division to
secondary oocyte production.
○ This will also trigger follicle rupture and ovulation.
■ However, the damage to the follicle and granulosa cells will lead to a
decrease in estrogen just the following ovulation.
○ Luteinizing hormone will help with the conversion of the follicle to the corpus
luteum.
■ The corpus luteum will secrete high amounts of progesterone and a little
bit of estrogen.
Luteal Phase
● Following ovulation, the corpus luteum secretes progesterone, estrogen, and inhibin.
○ These will feedback to the anterior pituitary gland to reduce luteinizing hormone
and follicle-stimulating hormone release.
○ The decrease in luteinizing hormone will lead to the degradation of the corpus
luteum after about 2 weeks unless pregnancy has occurred.
○ The corpus luteum regression leads to this precipitous drop in plasma
progesterone and estrogen concentrations.
■ This will lead to the shedding of the uterine lining or the menstrual phase
of the menstrual cycle.
● Do the cyclical fluctuations in sex steroid hormone concentrations do anything else?
○ Yes, it does

Menstrual Cycle
● It refers to a series of cyclical changes in the uterine endometrium.
○ It is to prepare the uterus for implantation if fertilization occurs.
● The events of the menstrual cycle are highly influenced by the hormones secreted
during the ovarian cycle.
● The first day of the menstrual cycle is the first day of menstrual bleeding.
● 3 Phases
1. Menstrual phase
2. Proliferative phase
3. Secretory phase

Menstrual Phase
 ● It lasts for about 3-5 days
○ This corresponds with the lowest level of ovarian hormones and gonadotropin,
● Due to the regression of the corpus luteum, estrogen and progesterone concentrations
decrease.
○ Menstruation is triggered by that precipitous decrease at the end of the luteal
phase.
● During menstruation, the uterus will shed all but the deepest layers of the endometrium.
○ As the endometrium is degraded, it will detach from the uterine walls and blood
will pass out through the vagina.

Proliferative Phase
● The proliferative phase corresponds with the mid to late follicular phase.
● During this phase, estrogen stimulates
○ Endometrial growth, vascular growth, and enlargement of the glands
○ Production of progesterone receptors by endometrial cells
○ Thinning of cervical mucus to facilitate passage of sperm

Secretory Phase
● During the secretory phase, the corpus luteum is secreting high amounts of
progesterone and a little bit of estrogen.
● During the early secretory phase, progesterone is responsible for
○ Converting estrogen-primed endometrium into a secretory tissue
○ Inhibiting uterine contractions
○ Making cervical mucus relatively impenetrable to bacteria
● Decreases in estrogen and progesterone are responsible for
○ Constriction of the uterine blood vessels and there is a decrease in oxygen and
nutrient delivery.
○ The disintegration of the endometrium
○ The uterus will begin to contract
○ There will be uterine artery dilation and this contributes to the blood loss that is
associated with the menstrual phase (50-150 mL).

Hormonal Birth Control

● Daily Pills
○ Combination pills (Estrogen and Progesterone)
○ Progesterone only pills
● Injections (Depo-Provera)
○ Progestin-only that can be given either intramuscularly or subcutaneously.
○ It will help to prevent pregnancy for approximately 3 months or so.
● Mechanisms
○ It prevents ovulation and uterine changes that facilitate implantation.

● It is very common for women who are using hormonal birth control to either have very
 light menstrual cycles.
○ In the case of injections, it completely skips menstrual cycles for 3-6 months.
● Is the lack of menstrual bleeding an issue?
○ The answer is no because of the pattern of hormone secretion.

Systemic Effects of Estradiol

● Brain
○ Temperature regulation
○ Protective against dementia
○ Promotes to be physically active
● Cardiovascular System
○ Estrogen upregulates nitric oxide production (vasodilator)
○ It decreases platelet aggregation
○ It attenuates vascular smooth muscle proliferation
■ It reduces atherosclerosis and cardiovascular disease
● Liver
○ It improves cholesterol profile by increasing HDLs and decreasing LDLs
● Bone
○ It has favorable effects to maintain bone mineral density
● Estradiol has a favorable effect on the immune system.
○ That is one of the reasons why females statistically do not get sick quite as
frequently as males.
○ However, it is commonly found that for people who have an autoimmune disease
the majority of them tend to be female.

Menopause
● It is the loss of menstrual cycles for at least one year.
● The average age for menopause to begin is about 51 or so.
● Perimenopause begins approximately 4-10 years earlier
● Cause
○ Depletion of viable ovarian follicles
■ There is a decrease in estrogen and progesterone secretion.
○ There is a compensatory increase in FSH and LH secretion
● Physiological Consequences
○ Irregular periods (shorter or longer) and eventually the woman will cease to have
the menstrual cycle and will become infertile.
○ Hot flashes and night sweats
○ Sleep problems
○ Mood changes
○ Slowed metabolism and weight gain
○ Thinning hair and dry skin
○ Increased risk in cardiovascular diseases