NBDE Biochemistry

Notes.
What you need to know for the NBDE. Don’t stress, just relax and PASS.
 Biological Compounds Notes

Carbohydrates end in “ose” (example glucose, sucrose….)

All disaccharides are made of monosaccharides. One of the monosaccharides will be glucose +
another monosaccharide

Examples of disaccharides are:

Sucrose = glucose + fructose

Maltose = glucose + glucose

Lactose = glucose + galactose

Brush border of the small intestine: here you will find enzymes that can break down
macromolecules (large things) to micromolecules (small things). An example would be the
digestive enzyme, sucrase which breaks down the disaccharide sucrose into two
monosaccharides (glucose and fructose). Just remember that the brush border increases the
surface area and this helps to increase the likelihood of absorption of nutrients such as (fatty
acids, amino acids, monosaccharides etc.. ).

Polysaccharides = means more than 10 monosaccharides

Reducing Sugars = these sugars have the ability to reduce something. Reduction is the gain of
an electron or the gain of a hydrogen. This means they act as a reducing agent. If the sugar is a
reducing agent, that means the reducing sugar itself is oxidized. An example is:

In the above illustration, “A” goes from a zero charge to a +1 charge. Remember electrons are
negative, so to go from a zero charge to a +1 (we became more positive). To become more
positive you must lost an electron, which called oxidation. Reduction would just be the reverse
and represented by “B” in the above drawing. The item that is oxidized is also the reducing
agent and the one that is reduced is the oxidizing agent. If you have an oxidation, then you will
have a reduction (this is called a redox reaction).

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Most reducing sugars have an aldehyde group as seen below. An aldehyde has R group, a
carbonyl group and a hydrogen.

An example to better understand oxidation and reduction: Imagine two people standing up in
front of one another. One person (Mary) has a banana in her hand and the other person (John)
has nothing in his hand. The banana represents an electron which is negative. If Mary gave the
banana to John, Mary would lose her electron or her negative charge (she was oxidized). Since
John gained the banana (electron), he was reduced. Now the question becomes, who was
responsible for causing John to be reduced? That’s right, it was Mary, she was the one that
reduced John. So not only was Mary oxidized, but she is also the Reducing Agent because she
caused the reduction. One mnemonic commonly used is OiL RiG which stands for Oxidation
Lose electron and Reduction Gain electron.

Dextrans – are polysaccharides composed of glucose units connected by straight chain alpha
1,6 linkages. The easiest way to remember that it is alpha 1,6 linkage is to think of the structure
of glucose which has a six (6) carbon chain. Dextran is synthesized from sucrose by certain
bacteria such as Leuconostoc mesenteroides and Streptococcus mutans. Dental plaque is rich in
dextrans. If an enzyme has the word sucrase in it, then it can create a dextran and a levan.
Sucrose glucosyltransferase creates Dextrans.

Dextrans (glucose) and levans (fructose) are derived from sucrose (disaccharide).

Amylases – Are enzymes that break down starches into sugars. They can be found in the mouth
or the pancreas. Alpha amylase is secreted from the salivary glands an pancreas. All the
amylases have an alpha 1,4 linkage except gamma amylase which can have a 1,6 linkage in
addition to the 1,4.

Glycogen – is the storage form of glucose in the liver. The glycogen is linked by 1,4 linkages or
what is called a glycosidic bond, but can have branches via 1,6 linkages. Just remember that 1,6
sounds like more than 1,4. And what do we have more of? That’s right, Branches. Therefore the
1,4 must be the linear links while we see 1,6 in branches.

What would happen if you could not break the bonds in glycogen? Of course the glycogen
would build up in the liver causing hepatomegaly. There are other enzymes that if they were
deficient could cause this same build up in the liver.

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Glycogen storage diseases (Very Hot CAMP). Where is the glycogen when you need it?
Remember that these diseases are genetically recessive conditions

Disease Enzyme Deficiency Characteristics

Very Von Gierke's glucose-6-phosphatase Lactic acidosis, hyperuricemia
disease
Hot Hers' disease liver glycogen
phosphorylase
C Cori disease glycogen debranching
enzyme
A Andersen Glycogen branching enzme
M McCardles Muscle phosphorylase Renal failure by myoglobinuria
Poor Pompe acid alpha-glucosidase heart failure

ABCD = Anderson Branching enzyme deficiency – Cori Debranching enzyme deficiency.

Inulin – is a sugar (fructose) that is used to measure GFR (glomerular filtration rate). GFR is
basically how the kidney filters substances. Inulin is the best measure of GFR. The formula for
GFR is:

Glycosaminoglycans (GAG) you need to know

 Hyaluronic Acid = Hi I have not sulfur - Does not contain sulfur

 Chondroitin sulfate = Covers everything – Most Abundant GAG
 Heparan sulfate = Put the liver in the basement – Hep (liver) found in basement
membrane.
 Heparin – anticoagulant (used to dissolve blood clots)
 Dermatan and Keratan sulfate

What happens if the something goes wrong with the lysosomes needed to break down the
glycosaminoglycans? We call these conditions mucopolysaccharide storage diseases:

Hunter Feel More Hurt when they don’t tell a Ly

Lysosome deficiency

Hunters – Hunters put an X on their target (X-linked recessive condition) and then RUN away

Sanfillipo – Second start with the letter “S” just like Sanfillipo starts with the letter “S”

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Morquio – More can mean less. The individuals have less height

Hurlers – Hurlers should mean Hurters because it’s very similar to Hunters, but has a worse
outcome.

Condition Enzyme deficiency Characteristics

Hunters Idurunate sulfastate X-linked recessive
(iduronate sulfatase)
Hurlers α-L-iduronidase Autosomal recessive
Mental retardation,
macroglossia, corneal
clouding, cardiomyopathy,
hepatosplenomegaly,

San Fillipo A-D types Glucosamine will be Hyperactive. Death by second

Morquio syndrome A and B
associated with the enzyme year of life
name in Sanfillipo B-D
Galactosamine will probably Skeletal dysplasia. They will
be in the name of the enzyme be short.
somewhere

Salivary glands and secretions

SubMandibular – is serous and mucous secretion (mixed)

Sublingual – mucous
Parotid – Serous
Von Ebner’s – serous

When your mouth waters (meaning you are anticipating food) = increased digestion. You
should think of parasympathetic nervous system. Parasympathetic = serous secretion and
sympathetic = mucous secretion.

Amino Acids

Amino acids are the building blocks of proteins. For the NBDE you will want to know all the
essential amino acids and their derivatives. Below are some helpful ways to remember them.

Essential amino acids are easily remembered from the PVT TIM HaLL. Essential amino acids
means you have to take them in through the diet.

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Phenylalanine Pathway -

Valine – Think about a female named Val who can’t swim because her bones hurt due to sickle
cell and like all females, she is sweet. That means that Valine is hydrophobic (can’t swim and
doesn’t like water). She has sickle cell (Valine replaces glutamic acid which is hydrophilic
causing the hemoglobin to have an abnormal aggregation). Val is one of the amino acids
responsible for maple syrup (sweet) urine disease.

Threonine – I have only had Three beers (alcohol) officers. This means that threonine has an
alcohol group attached to it.

Tryptophan pathway – Sarah (SEROtonin) and Mel (Meltonin) tripped over the fan
(tryptophan). Serotonin is a neurotransmitter released from enterchromaffin cells and helps
with mood. When serotonin is low, you are depressed when it is higher you feel good.
Melatonin regulates your sleep wake cycle (circadian rhythm). This is found associated with
such foods as turkey.

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Isoleucine and Leucine – this are two female cousins. Since they are females they are sweet
(can cause maple syrup urine disease) and afraid to swim (hydrophobic).

Methionine – is the start codon (AUG because school starts in August). Remember that a codon
is a set of three nucleotides that code for an amino acid. The codon AUG codes for the amino
acid Methionine.

Histidine – is one of the basic amino acids along with Arginine and Lysine. An easy way to
remember the basic amino acids is to the think about the movie “Shallow HAL”. Shallow means
basic and HAL in the movie was a basic man that only was attracted to outer beauty. So
everyone began to call him shallow or basic HAL. The three letters represent the amino acids
that are basic (Histidine, Arginine and Lysine). Remember the L is for lysine, because HAL would
like to the women to get what he wanted.

Those are all the Essential Amino Acids

Ketogenic Amino Acids – Keto starts with the letter K, the letter that comes after K in the
alphabet is “L”. That means the Ketogenic amino acids start with the letter “L” (Leucine and
Lysine).

Both ketogenic and glucogenic amino acids – Both means double think of the word PITT with
double “T”s at the end of the word. Phenylalanine, Isoleucine, Tyrosine and Tryptophan.

Guess what? If it doesn’t fall into Ketogenic or Both amino acid categories, then it must be a
glucogenic amino acid. There are a lot of glucogenic amino acids, but no need to memorize
these when you know the two categories listed above.

Acidic Amino Acids – The good news is there are only two acidic amino acids which are
(glutamic acid and aspartic acid). These two almost always go together in a question. So if you
have a multiple choice question and two of the answers glutamate or aspartate, eliminate both
as an answer choice because they tend to go together. However, if there is an answer that says
both glutamate and aspartate, don’t eliminate it. For the NBDE they won’t get to deep into
distinguishing glutamic acid from aspartic acid.

What is the smallest amino acid that is both hydrophobic and hydrophilic? Glycine

Which amino acid is used as a collagen cross-linker? Lysine or hydroxylysine

Which amino acids give rise to norepinephrine and epinephrine? Phenylalanine and if
phenylalanine is not present, then tyrosine would take over as the essential amino acid in the
pathway and eventually make norepinephrine and epinephrine. NE and Epi are seen associated
with the adrenal medulla and a released in conjunction with the sympathetic nervous system.
Since the sympathetic nervous system is what happens when a hungry bear walks in your room

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(your pupils dilate, heart rate increases, blood pressure increases because of vasoconstriction,
blood rushes to your arms and legs so you can run. Finally you get a bronchodilation so you can
breathe in more oxygen). These sympathetic responses are associated with NE and Epi.

Amino Acid deficiencies –CPAA (Cystinuria, PKU, Albinism and Alkaptonuria)

A patient comes in for root canal and during their medical history you find that she has
recurrent problem with black urine. What do you suspect as the cause ? Cystinura
Cystinuria is the inability to absorb what ? Cysteine, ornithine, arginine, lysine (COAL).

Which AA deficiency causes decreased skin pigmentation and patient can eat anything with
asparagine in it. They must also stay away from things like nutrasweet or artificial sweetners?
PKU. When you have PKU, tyrosine becomes an essential amino acid.

What can cause black urine other than cystinuria? Alkaptonuria

Condition Amino Acid Deficiency

Alkaptonuria Homogentisic acid
Albinism Tyrosinase
Cystinuria Kidney defect of cysteine absorption
Phenylketonuria Phenylalanine hydroxylase

The protein collagen – is abundant throughout the body. It requires Vitamin C, which makes
sense, considering collagen starts with the letter “C”. If they ask on the NBDE about which
amino acids are associated with collagen, then you should look for answers that have the word
proline or lysine in it (hydroxyproline or hydroxylysine).

I (One). If you put the letter “B” in front of “one”, you get the word BONE which comes from
type one collagen, along with skin. Type one is the most abundant collagen. It is found in
tendons, skin, artery walls, cornea, the endomysium. Problems with type one can cause brittle
bone and skin diseases such as, Osteogenesis imperfecta, Ehlers–Danlos syndrome.

II. (two) This is for carTwolidge - Hyaline cartilage, makes up 50% of all cartilage protein.

III. This is the collagen of granulation tissue, and is produced quickly by young fibroblasts before
the tougher type I collagen is synthesized. Think of blood when you think of type 3

IV. (four) Basal lamina basement membrane. The basement is below the floor which rhymes
with the number four. Conditions associated with type four are: Alport syndrome,
Goodpasture's syndrome

V Most interstitial tissue, assoc. with type I, associated with placenta

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 The PDL is found in 1, 3 and 5
What condition is a result of Vitamin C deficiency and can give you bleeding gums. It can be
prevented with increased citric acid intake? Scurvy

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 Metabolism
What is metabolism? Metabolism is the breakdown (Catabolic) or building of something
(Anabolic). An example would be breaking down glucose to pyruvate. A building process would
be synthesizing proteins from amino acids.

What are the major categories of metabolism? You can metabolize (Carbohydrates, Lipid,
Proteins, Nucleotides).

Where does metabolism typically occur? Metabolism occurs inside the cell (intracellular). If
you think of the body being divided into two compartments (in the blood and not in the blood),
this will make things simple to understand.

How do things that need to be metabolized enter the cell? Things can enter the cell by simple
diffusion, facilitated diffusion, active transport.

 Diffusion = movement of things Down its concentration gradient.

– Simple diffusion does not need a protein transporter
– Facilitated = Finicky Friend helps (ex. Protein tansporters that are
selective).
• Ligand gated channels help open up other ion channels (ex
Acetylcholine ligand binds and open up Na+ channels.
 Active Transport
• Against its concentration gradient. Need energy (Directly or Indirectly)
– Directly = using ATP = called primary active transport

– Indirectly = called secondary active transport = Using the

concentration gradient of some other ion to help go against gradient.
(ex is Na+/Glucose symport. Sodium goes down it’s gradient into the
cell which allows glucose to go against its gradient into the cell.
 Osmosis
• Opposite side of water concentration (ex. When there is a lot of water we
say hypotonic, little water = hypertonic = high solute concentration). Water
moves toward things that are hypertonic.

What things can cross the cell by simple diffusion? Things that are small, uncharged (oxygen,
carbon dioxde, etc..) non-polar and hydrophobic. Since these things can cross the cell by simple
diffusion, their receptors must be located on the inside of the cell. Because the cell membrane is
composed of a phospholipid bilayer, and since things that are alike can diffuse, that means that
things that are hydrophobic can cross the hydrophobic phospholipid bilayer by simple diffusion.

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Examples of hydrophobic things are: lipids or steroids. Steroids tend will most likely end in the
letters “ol” or “one” (examples = testosterONE, cortisOL).

What is the purpose of enzymes in metabolism? Think of enzymes as (CATS), because like
CATS, they are quick and fast and for this reason, we say enzymes are CATalyst that can speed
up a chemical reaction. They speed up the reaction by lowering the activation energy. This is the
energy needed to move the reaction either in the forward direction toward products or the reverse
direction toward reactants. Think of the activation energy as a tall mountain. And you are on one
side of the mountain needing to get to the other side. If something could make the mountain
smaller you would be able to get to the other side quicker. A Catalyst is what makes the
mountain smaller and an enzyme is a catalyst.

What’s important to know about enzymes:

 Enzymes are CAT quick to speed up reactions. CATalyst

 Enzymes bind substrate (the reactants) through hydrogen and ionic bonds
 Substrate can bind to active site
 Something other than the substrate can bind to an allosteric site on the enzyme

The Goal of enzymes:

• Help the reaction reach Vmax

• If every willing substrate participates and fills the active site, Vmax is reached
• If even one active site is not full, you don’t reach Vmax
• As long as there is something in the active site, you will reach Vmax.
• The Enzyme does not discriminate on who can be at the active site. The substrate or a
competitive inhibitor can occupy the active site. (remember this)

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What is Vmax and Km? The rate of reaction when the enzyme is saturated with substrate is the
maximum rate of reaction, Vmax. The relationship between rate of reaction and concentration of
substrate depends on the affinity of the enzyme for its substrate. This is usually expressed as the
Km (Michaelis constant) of the enzyme, an inverse measure of affinity. Km is the concentration
of substrate which permits the enzyme to achieve half Vmax. An enzyme with a high Km has a
low affinity for its substrate, and requires a greater concentration of substrate to achieve Vmax.

What is competitive inhibition? Vmax remains the same, Km is increased

A competitor competes with the substrate for occupying the active site. Two ladies want one man
– not a pretty picture. The substrate is the main lady, but the competitor is pretty convincing.

It doesn’t matter to the enzyme who is at the activity site because he will still reach Vmax if
there is enough substrate concentration added.

What is non-competitive inhibition? Vmax decrease and Km remains the same

The other woman tries to sneak into the man’s heart by going to the back door (allosteric site). If
she is successful, then the front door (active site) will change its shape and the main woman
(substrate) can’t bind. This means the substrate can’t bind the active site, which leaves an empty
active site and a decrease in Vmax. No matter how much substrate you add it won’t matter
because the active site has changed.

What are some key enzymes and their functions:

Kinases:

• Anytime you see ATP, ADP, GTP, etc. used in a reaction, the enzyme that catalyzes the
reaction will be a Kinase. These are used for organic phosphates.

Phosphatase:

• Used when you are removing a inorganic phosphate, NOT in the presence of ATP

Phosphorylase:

• Used when you are adding an inorganic phosphate, NOT in the presence of ATP

DeHYDROGENase:

• Think about this when you are transferring Hydrogens to electron acceptors. For
example NAD+  NADH. Anytime you see NADH, FADH2 or NADPH, the enzyme
will be a dehydrogenase.

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Isomerase:

• If two things have the same number of atoms but are connected differently such as
glucose and fructose, they are considered isomers of one another. There is a more
technical way of saying this, but this is the general idea. The formula for Glucose is:
C6H12O6 and this is the same formula for Fructose. So if we convert Glucose 6-phosphate
to Fructose 6-phosphate, we will need to use an isomerase since we are working with
isomers.
•
The prefix of the enzyme will tell what it does in most cases: LIPase (metabolize lipids),
PROTEase (metabolize proteins), etc…

What does the enzyme substrate interaction look like and what is the ACTIVE site and
ALLOSTERIC site? The active site is where the substrate binds to the enzyme or where a
competitive inhibitor can bind to the enzyme. The allosteric site is where a non-competitive
inhibitor can bind to the enzyme. It’s the site that not the active site.

What is important to know regarding metabolism of glucose? In a nutshell (Glucose breaks

down to pyruvate which is converted to Acetyl CoA. Then Acetyl CoA combines with

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Oxaloacetate in the TCA cycle and turns the cycle twice for the 2 pyruvates generated in
Glycolysis. With one turn of the TCA cycle you generate 3 NADH, 2 FADH2 and 1 GTP. The
electrons from the intermediates of the TCA cycle are transported down the electron transport
chain. Oxygen will accept these electrons and form water and ATP.

Glycolysis

During glycolysis, glucose with six (6) carbons is broken down to two molecules of pyruvate
with each having 3 carbons.

Glycolysis occurs in the cytoplasm (cytosol) and does not require oxygen.

During glycolysis we use 2 ATP’s and make 4 ATP’s, which gives us a net yield of 2 ATP’s

Two hydrogen atoms are removed by NAD+ forming 2 NADH (Remember Dehydrogenase is
the enzyme used in this situation).

Additional phosphorylation results in intermediate 3-carbon molecules with 2 phosphate groups.

Four ATP are produced by substrate-level phosphorylation. Recall that substrate-level

phosphorylation is the production of ATP using energy from other high-energy compounds but
without the use of the electron transport system in the mitochondria.

The net yield of ATP in glycolysis is 2 for each glucose molecule (2 are used but 4 are
produced).

Two alternative pathways of glucose to remember are the Embden pathway (produces 2 ATP)
and Entner (produces 1 ATP).

Formation of Acetyl CoA

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Pyruvate produced by glycolysis (see above) enters the mitochondrion by active transport and is
converted to acetyl CoA as shown below. The remainder of the reactions of cellular respiration
occur in the mitochondrion.

pyruvate (C3) --> acetyl CoA (C2) + CO2

A carbon atom is removed from each of the pyruvate molecules forming a two-carbon compound
and CO2.

Each of the two-carbon compounds are oxidized forming NADH from NAD+.

Coenzyme A is attached to each of the two-carbon compounds producing two acetyl CoA
molecules.

Citric Acid Cycle

The citric acid cycle can be summarized by either of the diagrams below. The diagram below
occurs twice, once for each acetyl CoA.

Coenzyme A is removed when the two-carbon compound is attached to a four-carbon compound

producing a six-carbon compound (citrate).

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Each citrate molecule undergoes a series of reactions that removes 2 carbon atoms which are
released as CO2. In addition, 3 NADH, 1 ATP, and 1 FADH2 are produced. In addition, the four-
carbon compound that began the cycle is regenerated.

The diagram below also summarizes the citric acid cycle.

Electron Transport and Oxidative Phosphorylation

Mitochondrion structure

The inner membrane forms folds called cristae. These folds contain the carriers of the electron
transport system.

Acetyl CoA formation and the citric acid cycle occur in the inner space called the matrix.

The space outside the inner membrane is the intermembrane space. The electron transport
system pumps hydrogen ions (H+) into this space for oxidative phosphorylation.

Oxidative Phosphorylation

The electron transport system is found in the mitochondrion and chloroplast of eucaryotes and in
the plasma membrane of procaryotes. It consists of a series of carrier molecules which pass
electrons from a high-energy compound to a final low-energy electron acceptor. Energy is
released during these oxidation-reduction reactions to produce ATP.

The discussion below applies to the mitochondria of eucaryotes.

NADH or FADH2 bring electrons to the electron transport system in the mitochondria.

The system contains membrane-bound electron carriers that pass electrons from one to another.
When a carrier reduces another, some of the energy that is released as a result of that reduction is
used to pump hydrogen ions across the membrane into the intermembrane space. The remaining
energy is used to reduce the next carrier.

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As a result of the electron transport system, hydrogen ions become concentrated in the
intermembrane space. These concentrated ions contain energy much like a dam. The
enzyme ATP synthaseis able to use the energy of this osmotic gradient to produce ATP as the
hydrogen ions move under osmotic pressure through the enzyme back into the matrix of the
mitochondrion.

Oxygen is the final electron acceptor. The low-energy electrons that emerge from the electron
transport system are taken up by O2. The negatively charged oxygen molecules take up protons
from the medium and form water (2H+ + 2e- + 1/2 O2 --> H2O).

Summary of Glycolysis and Cellular Respiration

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Glycolysis

During glycolysis, glucose (C6) is converted to two pyruvates (C3).

C-C-C-C-C-C --> C-C-C + C-C-C

Formation of Acetyl CoA

One acetyl CoA is formed for each pyruvate produced by glycolysis (see the step above).

C-C-C --> C-C + CO2

pyruvate --> acetyl CoA + CO2

Citric Acid Cycle

C-C --> 2 CO2

The citric acid cycle produces NADH, FADH2, and ATP.

NADH and FADH2 carry electrons to the electron transport system.

Electron Transport System

In the electron transport system, NADH and FADH2 are oxidized and the energy is used to
produce ATP.

Total Yield

Glycolysis produces 2 ATP; aerobic respiration produces 34 more ATP

Substrate-Level Oxidative Total

Pathway
Phosphorylation Phosphorylation ATP
Glycolysis 2 ATP 2 NADH = 4 - 6 ATP 6 - 8
CoA 2 NADH = 6 ATP 6
6 NADH = 18 ATP
Citric Acid Cycle 2 ATP 24
2 FADH2 = 4 ATP
TOTAL 4 ATP 32 ATP 36 - 38

Fermentation

Without oxygen, cellular respiration could not occur because oxygen serves as the final electron
acceptor in the electron transport system. The electron transport system would therefore not be
available.

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Glycolysis can occur without oxygen. Although glycolysis does not require oxygen, it does
require NAD+. Cells without oxygen available need to regenerate NAD+ from NADH so that in
the absence of oxygen, at least some ATP can be made by glycolysis.

To regenerate NAD+ from NADH, the electrons from NADH are added to pyruvate to produce
alcohol (plants, yeast) or lactate (animals, bacteria).

The total ATP yield of fermentation comes from glycolysis; 2 ATP molecules are produced per
glucose.

Usefulness of Fermentation

Anaerobic exercise

During vigorous exercise, oxygen is consumed faster than it is needed. Additional ATP energy is
provided to the muscles by glycolysis and the result is a buildup of lactate in the muscles.

When lactate builds up, the blood pH drops and the muscles fatigue.

If you build up lactate, which is not a good source of energy it can be converted back to glucose
via the CORI cycle.

Yeast

Yeast produce alcohol which accumulates in their environment. As the concentration of alcohol
in their environment increases, it becomes more and more toxic to them. Beer and wine have a
maximum alcohol concentration because a higher concentration will kill the yeast cells.

Quick Review and Exercise

LIPIDS

 Saturated fatty acid = single bonds // unsaturated fatty acid = double bond(s)
 Bile salts = emulsifiers that help in fat digestion by forming water-soluble micelles

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  Chylomicrons = highest triacylglycerol content // LDLs = highest cholesterol content //
HDLs = highest protein content
 Ketone bodies = used as energy during when glucose is low; HMG-CoA synthase (rate
limiting/only in liver); cannot be used by brain
o Ketosis = fatty acids are incompletely metabolized - complication of starvation,
fasting, alcoholism
 Diabetic ketoacidosis = complete absence of insulin in type 1
 Fatty acid synthesis begins with acetyl-CoA (glucose is major source) and occurs in
cytosol [malonyl-CoA = committed step]
 Triglyceride = energy source (3 fatty acids + glycerol)

METABOLISM

 Glycolysis (glucose  pyruvate) - cytoplasm; 2 ATP  citric acid cycle (TCA/krebs

cycle) - mitochondrial matrix; 2 ATP  oxidative phosphorylation (electron transport
chain) - mitochondrial inner membrane; 32-34 ATP = 36-38 ATP
 Electron transport chain: 2 H + 2 e + ½ O2  H2O + energy // proton gradient used to
produce ATP
 Cori cycle: liver converts lactate formed by active muscle back into glucose
 Pentose phosphate pathway:
o Oxidative: NADPH (glucose-6-phosphate dehydrogenase) // irreversible
o Non-oxidative: ribose-5-phosphate (transketolase/transaldolase) // reversible

ATP not involved

What is the enzyme that is associated with the following:

1. NADH or NADPH: ______________________________

2. FADH2: _________________________
3. ATP, ADP or AMP (add or removing a phosphate group: ___________________
4. Conversion of Glucose to a Fructose: ___________________________________
5. Used in the formation of an aldehyde: ______________________________

What is the slowest step in glycolysis (rate limiting enzyme) ? _______________________

What would happen to the rate of glycolysis if you have an increased ADP/ATP ratio?
_____________________________________________________________________________

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 Molecular Biology Notes
Nucleotides

DNA and RNA come from nucleotides

Nucleotides consist of three parts:

1. Sugar – pentose (meaning 5 carbon sugar)
Either Deoxyribose or Ribose
2. Base – which is a nitrogen ring
3. Phosphate group
4.
There are four bases in DNA and RNA which are broken into:

Purine (pure As Gold) Adenine and Guanine

Pyrimidines (CUT the PY) Cytosine, Uracil (Which replaces Thymine in RNA). So in RNA instead
of having Thymine you have Uracil.

In a DNA structure the bases pair from the outside in. This means that A=T or U and C=G. A-T or
U bond is a double hydrogen bond and the C-G bond is a triple hydrogen bond.
Which bond will be harder to break? The C-G bond because of the triple bond. That means it
will require a higher melting point and the bond length is shorter.
A
C
G
T or U

There is a rule called Charcaff’s rule. It means that if you have 20% A then you will have 20% T
since they bond together in a DNA double helix. The same goes for C and G bond. Just
remember they will have equal amounts if they are bonded together. Because the double helix
consist of purines and pyrimidines you should be able to calculate the amount of any base
present.

Example: If you have 30% A, how much G will you have? The answer is 20% because 30% A
means 30% T which = 60%, this leaves 40% remaining to be split between C and G equally.
The combination of a base and a pentose is called a nucleoside. If you have a sugar, base and
phosphate group attached we call this a nucleotide.
For DNA, these are dATP, dGTP, dCTP, and dTTP.
For RNA, these are ATP, GTP, CTP, and UTP.

Fluorouracil - Pyrimidine Analog. Acts Suicide Inhibitor of Thymidylate Synthase (the enzyme
that converts dUMP to dTMP). 5-FU acts in several ways, but principally as a thymidylate
synthase (TS) inhibitor. Interrupting the action of this enzyme blocks synthesis of the

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pyrimidine thymidine, which is a nucleoside required for DNA replication. Thymidylate
synthase methylates deoxyuridine monophosphate (dUMP) to form thymidine
monophosphate (dTMP). Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing
cancerous cells undergo cell death via thymineless death.

What is the first step in the repair in pyrimidine dimers? The answer would be cleavage using
an endonuclease which is an enzyme that cleaves from the inside of the DNA strand. The
pyrimidine dimer is the major photoproduct produced in DNA after UV irradiation. Ever since
the repair of UV damage was first described, the pathway for the excision repair of these
adducts was presumed to consist of four steps: incision near the damage site; excision of the
damaged nucleotides; replacement of the missing nucleotides by DNA polymerase and finally
ligation.

Which recognizes specific DNA sequences? Restriction endonucleases. Restriction enzymes

recognize a specific sequence of nucleotides and produce a double-stranded cut in the DNA.

Purines such as adenine and guanine can undergo degradation as seen in the image below:

The final product in purine degradation is: Uric Acid. You should also understand that the
conversion of xanthine to uric acid requires an enzyme called xanthine oxidase. If you block this
enzyme with a drug like (allopurinol) it can help with the treatment of gout. Gout is just a build
up of uric acid.
What drug inhibits DNA dependent RNA polymerase? Rifampin which is a drug we use for
tuberculosis.
RNA

21
There are three different types of RNA to remember for the NBDE.
tRNA – the “T” stands for tiny. It’s the smallest of the RNA’s and it carries the anticodon which
binds to the codon on the mRNA.
mRNA – the “M” stands for massive. It’s the largest RNA and carries the codon.
rRNA – the “R” stands for rampant. This means it’s the most abundant RNA
What is a codon? A triplet of adjacent nucleotides in the messenger RNA chain that codes for a
specific amino acid in the synthesis of a protein molecule. Compare anticodon.

Enzymes involved in DNA replication

1. Helicase: unwinds the DNA
2. Primase: adds an RNA primer to the DNA template to begin replication
3. DNA polymerase: elongates the strand
4. DNA Ligase: seals the gaps of the okazaki fragments on the lagging strand
5. DNA gyrase or topoisomerase: relieves the strain and prevents supercoiling of the DNA
strand. Certain drugs can block the actions of DNA gyrase in bacteria. An example of an
antibiotic is Ciprofloxacin.

Transcription – the conversion of DNA to mRNA

Translation – the translation of mRNA codons into proteins

Mutations:
Three Point mutations means that a single nucleotide is affected in a codon. Typically it
happens at the third position (whobble position). Examples of point mutations include:

a. Missense – a single nucleotide change causes a new amino acid to be formed

a.
b. Silent – a single nucleotide change does not cause a change in the amino acid

a.

22
 c. Nonsense – think of Nonsense as Nonstop because here a single nucleotide change can
create a stop codon. Imagine you are translating codons into a growing protein. As long
as there is no stop codon, the protein will continue to grow, but as soon as a stop codon
is recognized the protein will stop growing.

There are three stop codons.

UGA – U Go Away
UAA – U Are Away
UAG – U Are Gone

Transverse mutation – is the replacement of a purine with a pyrimidine or vice versa

Transition mutation – is the replacement of a purine with a purine or a pyrimidine with a
pyrimidine. The “i” in transition means identical switch.
Frameshift mutation happens when you either insert or delete a nucleotide in a reading frame
and it shifts the entire frame.

You make be asked about blotting techniques on the NBDE, but they are simple to remember if
you use the mnemonic SNoW DRoP. These techniques help to identify either DNA, RNA or
proteins.
Southern DNA
Northern RNA
O O
Western Proteins

23
 Molecular Quick Review
DNA/RNA
 DNA polymerase: adds RNA primer chains required for DNA polymerase (does not
require a primer itself)
 DNA polymerase: reads from 3’5” and replicates from 5’3’
 Nuclease (endo or exo): cleaves phosphodiester bonds
 DNA ligase: joins together Okazaki fragments
 Topoisomerase: unwind DNA
 DNA gyrase: re-wind DNA
 Reverse transcriptase: RNA-directed DNA polymerase in RNA viruses (like HIV) that
allows the formation of DNA from viral RNA so it can be incorporated into the host DNA
[AZT is a competitive inhibitor of this]
 Nucleotide = nitrogen base + sugar + phosphate (nucleoside = nitrogen base + sugar)
o Purines = A + G [larger; excreted as uric acids] // pyrimidines = T + C + U (RNA)
 DNA double helix
o Anti-parallel // hydrophilic // polar
o Hydrogen bonding + base-stacking interactions = double helix stability
 A-T = 2 hydrogen bonds // G-C = 3 hydrogen bonds [higher melting
temperature]
 Codons: start = AUG (methionine) // stop (nonsense) = UAA, UAG, UGA
 Transcription = DNA  mRNA
 Translation = mRNA  amino acids  protein
 rRNA = major components of ribosomes on which protein molecules are assembled
[most abundant]
 tRNA = carries amino acids to ribosome; amino acids are linked together based on
mRNA codon; amino acyl-tRNA synthetase
 mRNA = carries codon from DNA in nucleus to ribosomes for translation [least
abundant]

24
 Membranes

MEMBRANES
Plasma membrane = lipid bilayer of lipids (mainly phospholipids) + proteins
(globular: peripheral + integral); “fluid-mosaic”; non-covalent hydrophobic
interactions; highly impermeable (only permeable to small (ex.. water and gases),
uncharged (ex.. carbon dioxide, oxygen) and hydrophobic (ex.. cholesterol
derivatives like steroid hormones).

The plasma membrane bilayer of humans have hydrophobic tails and hydrophilic
heads.

The major NBDE topic about membranes are the receptors located on the
membrane. Think of it like this (The membrane protects the inside of the house
which is the inner cell and its contents. Some things can go directly into the house
or cell without needing a receptor on the membrane, they can bind to their
receptor once they are on the inside of the cell. On the other hand some things
that are hydrophilic, large, or charged cannot come directly into the cell,
therefore they will need to communicate to the inside of the cell through a
second messenger:

Example:

Protein and peptide hormones, catecholamines like epinephrine, and eicosanoids

such as prostaglandins find their receptors on the plasma membrane of target
cells. (Because they are hydrophilic and can’t cross cell membrane by simple
diffusion).

Binding of hormone to receptor initiates a series of events which leads to

generation of so-called second messengers within the cell (the hormone is the
first messenger). The second messengers then trigger a series of molecular
interactions that alter the physiologic state of the cell. Another term used to
describe this entire process is signal transduction.

25
Second Messenger Systems

Consider what would happen if, late at night, you noticed a building on fire.
Hopefully, you would dial 911 or a similar emergency number. You would inform
the dispatcher of the fire, and the dispatcher would, in turn, contact and
"activate" a number of firemen. The firefighters would then rapidly go to work
pouring water on the fire, setting up roadblocks and the like. They would also
probably activate other "players", such as police and fire investigators that would
come in later to try and determine the cause of the fire. Importantly, once the fire
is out (or the building totally destroyed), the firemen go back to the station and to
sleep.

The community response to a fire is, at least in some ways, analogous to a second
messenger system involved in a hormone's action. In the scenario described, you
are the "first messenger", the dispatcher is "receptor", the firefighters are
"second messengers".

Second Messenger Examples of Hormones Which Utilize This System:

Cyclic AMP Epinephrine and norepinephrine, glucagon, luteinizing hormone,

follicle stimulating hormone, thyroid-stimulating hormone, calcitonin, parathyroid
hormone, antidiuretic hormone.

Protein kinase activity: Insulin, growth hormone, prolactin, oxytocin,

erythropoietin, several growth factors.

Calcium and/or phosphoinositides: Epinephrine and norepinephrine, angiotensin

II, antidiuretic hormone, gonadotropin-releasing hormone, thyroid-releasing
hormone.

Cyclic GMP: Atrial naturetic hormone, nitric oxide

In all cases, the seemingly small signal generated by hormone binding its receptor
is amplified within the cell into a cascade of actions that changes the cell's
physiologic state. Presented below are two examples of second messenger
systems commonly used by hormones. The examples used are of glucagon and
insulin, both of which ultimately work through a molecular switch involving

26
protein phosphorylation. Be aware that in both cases, a very complex system is
being simplified considerably.

Cyclic AMP Second Messenger Systems

Now, let's put this information together to understand the mechanism of action
of a hormone like glucagon:

1. Glucagon binds its receptor in the plasma membrane of target cells (e.g.
hepatocytes).
2. Bound receptor interacts with and, through a set of G proteins, turns on
adenylate cyclase, which is also an integral membrane protein.
3. Activated adenylate cyclase begins to convert ATP to cyclic AMP, resulting
in an elevated intracellular concentration of cAMP.
4. High levels of cAMP in the cytosol make it probable that protein kinase A
will be bound by cAMP and therefore catalytically active.
5. Active protein kinase A "runs around the cell" adding phosphates to other
enzymes, thereby changing their conformation and modulating their
catalytic activity - - - abracadabra, the cell has been changed!
6. Levels of cAMP decrease due to destruction by cAMP-phosphodiesterase
and the inactivation of adenylate cyclase.

In the above example, the hormone's action was to modify the activity of pre-
existing components in the cell. Elevations in cAMP also have important effects on
transcription of certain genes.

27
 Nervous System
Cranial Nerves: It is important to know the cranial nerves and whether they are sensory, motor
or both. Below you will find a simple way to remember.

There are nerve tracts that send information either to the brain to be processed or away from the
brain to activate something in the periphery such as muscles. The mnemonic SAME helps to
remember the connection between sensory and motor. SAME = Sensory Afferent Motor
Efferent. If you see (GSE which is General Somatic Efferent) you should be thinking of motor
nerve fibers going away from the brain. Sensory sends information toward the brain.

Of the somatic efferent neurons subtypes:

Alpha motor neurons (α) target Extrafusal muscle fibers.

Gamma motor neurons (γ) target Intrafusal muscle fibres

AEGI (listed in alphabetical order) -

S = sensory, M = motor, B = both (motor and sensory)

1. On - Olfactory - Some
2. Old - Optic - say
3. Olympic - Occulomotor - Marry
4. Towering - Trochlear- money
5. Tops - Trigeminal - But
6. A - Abducens - my
7. Fin - Facial - brother
8. And - Auditory - says
9. German - Glossopharyngeal - big
10. Viewed - Vagus - brains
11. Some – Spinal Accessory - matter
12. Hopps - Hypoglossal - most

A patient who has damage to the right hypoglossal nerve will protrude the tongue in which
direction? Right. Lesion of the hypoglossal nerve causes the tongue to deviate toward the side of
the lesion.

A patient with absent direct and consensual light reflexes, but normal eyesight, is most
likely to have a lesion on what cranial nerve? Occulomtor. The key to answer this question is
understanding which nerve is response for the pupil reflex (consensual light reflexes). The fact
that the patient has normal eyesight, rules out the optic nerve as the cause. An easy way to

28
remember the nerves that affect the eyes is that the lateral rectus is innervated by cranial nerve
six (6) and the Superior oblique is innervated by cranial nerve (4). Remember LR6SO4, looks
like a chemical equation. All other muscles of the eye are innervated by oculomotor (cranial
nerve 3).

What are the characteristics of the sympathetic Nervous system? Thing of a hungry bear that
walks into your room. What would happen to your pupils (dilate-midriasis), What would happen
to your heart rate and blood pressure (increase), What would happen to your digestion, unless
you plan to eat the bear, your digestion would decrease, which means all things dealing with
digestion decrease such as saliva production, vagus nerve activity, acid production in the
stomach etc). Blood would rush to your arms and legs so you can run from the bear.

Pupil dilation (midriasis)

Decreased digestion

Increased heart rate

Increased blood pressure

Vasoconstriction

Increased Lipolysis

Activation of Alpha-1,Beta-1,Beta-2 receptors

Adrenergic receptors should make you think of sympathetic. The mnemonic is (KISS, but the
K is substituted with a Q). Only alpha-2 will inhibit the sympathetic nervous system when an
agonist is present. (Remember that an agonist will make the receptor do what it is designed to
do). For example: a beta-2 agonist will causes the pupils to dilate because it will stimulate the
sympathetic nervous system.

Q uiet - alpha 1

I nhibitory - alpha 2

S timulatory - beta 1

S timulatory - beta 2

29
Muscarinics receptors - Think of acetylcholine and cholinergic responses such as SLUDS

S - salivation

L - lacrimation

U - urination

D – defacation, diarrhea
S -sweating

Remember if you see the neurotransmitters norepinephrine, epinephrine which is noradrenaline

and adrenaline (adrenergic) respectively, you should be thinking of the sympathetic nervous
system. These are also considered catecholamines. These are found in the post-ganglionic
neurons.

A ganglion is a collection of nerve cells. Acetylcholine is found in the pre and post ganglions of
parasympathetic and also the pre ganglion of the sympathetic. Parasympathetic have a long
Preganglionic and short postganglionic.

What is Monoamine oxidase (MAO)? Catalyzes the breakdown of catecholomines such as

epinephrine, norepi, and serotonin. These monoamines are typically associated with the adrenal
medulla.

Spinal tracts - If the tract begins with the word “Spino” it’s sensory. If it ends with the word
“spinal” its motor. An example would be the Spinothalamic tract which sensory (responsible for
pain and temperature sensations). Or the Rubrospinal tract which is motor (responsible for large
muscle movement as well as fine motor control). Sensory tracts are ascending, while motor tracts
are descending.

Basics of cell depolarization and action potentials: a cell will become excited when the inside
of the cell becomes more positive than the outside of the cell. Typically at rest, the inside is more
negative than the outside for a couple of reasons. (1) The inside of the cells has negatively
charged proteins, (2) there is a sodium potassium pump that pushes three positive sodium ions
out of the cell and brings in 2 positive potassium ions inside the cell. As you can see if I push out
more positive sodium and bring in less positive potassium, the outside will be more positive (AT
REST). The resting membrane potential is somewhere between -60 to -70 mV.

30
Depolarization – happens when the cell membrane becomes permeable to sodium or other
positive ions like calcium. When sodium or calcium rush inside the cell, the inside of the cell
becomes more positive, leading to depolarization and an action potential. This action potential
travels down an axon to a synaptic terminal or bulb where it will release a neurotransmitter that
can act on junctions, such as the neuromuscular junction causing muscle contraction.

What would happen if you block the sodium potassium pump with digoxin? The cell would
depolarize because you are blocking the three sodium ions from leaving the cell. Since the
sodium stays inside the cell, the inside becomes more positive, leading to depolarization and an
action potential, eventually causing a muscle to contract.

What is absolute refractory period? The period after an initial action potential has happened
when no matter how strong the next stimulus, you cannot generate another action potential. This
is different from relative refractory period which means that if you have a strong enough
stimulus, you can generate another action potential.

Describe Myelin? A sheath that helps the propogation or movement of an action potential along
the axon. Myelin in the periphery produced by shwann cells, while Myelin in the brain is
produced by oligodendrocytes.

A woman comes in with recent complaints of muscle weakness in her upper extremities and
drooping eyelid. What is the first thing that comes to mind? Myasthenia Gravis. Is this an
autoimmune disorder? Yes. How does physostigmine drugs help in the treatment?
Physostigmine inhibits acetylcholinesterase enzyme. This enzyme normally breaks down

31
acetylcholine (ACH). Keep in mind that the reason she is having muscle weakness is become the
acetylcholine receptors are not as sensitive to acetylcholine as they should be. So one way to
correct the problem is to increase the amount of acetylcholine present at the receptors. The more
acetylcholine there, the more likely the receptor will bind the ACH. By blocking
acetylcholinesterase, you block the breakdown of acetylcholine.

Rods vs Cones - Rods sense dim light (these are activated when you are reading in the dark).
Cones sense vivid colors (daylight). Occipital lobe is the visual cortex

What are the five basic taste? Sweet, Sour, Bitter, Salt, Umami (remember the answer on the
test will have something to do with glutamate)

Which taste buds are not keratinized? Foliate, Fungiform

What are the excitatory neurotransmitters? Norepinephrine, Acetylcholine, Glutamate (I am

excited when my wife does not NAG about my Gluteals)

What are the inhibitory neurotransmitters? Glycine and GABA

Heat - ConDuction = Direct contact exchange of heat and Convection = heat currents circulate in
the air.

• The limbic system: Amy the gymnast is limber and very emotional.

• The five “F” of the limbic system: Feeling, Fleeing, Fighting, Feeding and Sex

• Structures in the limbic system:

– Amygdala

– hypoCampus = Go to campus for learning and memory

– Mammillary bodies

Basal Ganglia (BG) Body Grooving – grooving means movement. Component of the
Basal Ganglia:

– Striatum (caudate + putamen) = receives input from other brain areas, but only
sends information to the BG

– Substantia Nigra = Dopamine location

– Pallidum = Prevents (inhibits other motor areas)

32
Main purpose is to have voluntary control of body movement.

A 41 year old male comes into your dental clinic with an intention tremor and shaking at
rest. His gait is abnormal when walking. You suspect that dopamine levels are affected.
Which of the following is the most likely condition? Parkinson’s disease

Cerebellum - Think of the drunk man pulled over by the police. These are the signs of
cerebellum damage. Can’t walk a straight line, Eye movement jerky (nystagmus) and Can’t
count on his fingers (fine motor movement impaired).

Brain Nuclei (MPM) - All have (4) nuclei except the midbrain = mid = middle (1/2 way
between is (2) nuclei

Mid = cranial nerve 3, 4 nuclei

Pons = cranial nerve 5,6,7,8 nuclei

Medulla = cranial nerve 9,10,11,12 nuclei

What innervates the thumb? Median nerve

What innervates the serratus anterior? Long Thoracic Nerve

One of the questions that may appear on the exam may ask which of the following is NOT
derived from neural crest cells? The answer will probably be enamel. The odontoblast ARE
derived from the neural crest cells.

33
Nervous system quick review
 Saltatory conduction = myelinated with nodes of ranvier  faster + consumes less
energy

o CNS = oligodendrocytes // PNS = Schwann cells

 Action potential:

o All-or-none

o Na/K pump (3 Na out/2 K in) + leak channels = resting membrane potential (-70
mV)  more negative inside cell

o Threshold reached  VG Na channels open and Na enters  depolarization 

VG Na channels close + VG K channels open and K leaves  repolarization 
hyperpolarization (refractory period)

o Action potential  depolarization  influx of calcium  release of NT (ACh)

o *Local anesthetics:  permeability of Na (non-depolarizing nerve block)

 ANS (involuntary // 2 nerve fibers):

o Sympathetic:

 Thoracolumbar (T1-L2)

 Paravertebral or prevertebral ganglia

 Preganglionic = ACh (nicotinic)

 White rami communicans = myelinated preganglionic sympathetic

 Postganglionic = NE [exceptions: ACh for sweat glands, piloerector

muscles of hair, and some BVs]

 Gray rami communicans = unmyelinated postganglionic

sympathetic

 Diffuse

o Parasympathetic:

 Craniosacral (CN III, VII, IX, X; S2-4)

34
  Terminal ganglia in/near organ [ciliary (III), pterygopalatine (VII),
submandibular (VII), otic (IX), X on each organ]

 Preganglionic = ACh (nicotinic)

 Postganglionic = ACh (muscarinic)

 Specific

o Oppose each other EXCEPT for in salivary glands

 Epi =  and  receptors // NE = mainly  receptors

o 1 = smooth muscle contraction

o 2 = decrease insulin + NE release

o 1 = increase HR/CO of heart

o 2 = smooth muscle relaxation

 Ascending tracts (sensory)

o Lateral spinothalamic - pain, temperature, crude touch [contralateral]

o Anterior spinothalamic - crude touch and pressure [contralateral]

o Fasciculi gracilis and cuneatus - discriminating touch, pressure sensations,

conscious kinesthesia [ipsilateral]

o Anterior and posterior spinocerebellar - unconscious kinesthesia [ipsilateral]

 Descending tracts (motor)

o Pyramidal (direct and monosynaptic)

 Corticospinal*  voluntary motor movement

 Lateral = contralateral

 Anterior = ipsilateral

 Corticobulbar  impulses to cranial nerves (for mastication, facial

expression, swallowing, etc.)

o Extrapyramidal  balance and muscle tone

 Lateral reticulospinal - facilitatory

35
  Medial reticulospinal - inhibitory

 Rubrospinal - coordination of body movement and posture

Vestibulospinal - posture and balance

36
 Muscle

There may be a question about which muscle is attached to the coronoid process (temporalis)

In humans, it arises from the temporal fossa and the deep part of temporal fascia. It passes
medial to the zygomatic arch and forms a tendon which inserts onto the coronoid process of the
mandible, with its insertion extending into the retromolar fossa posterior to the most distal
mandibular molar.

There may be a question about the muscles that form the “sling” (medial pterygoid, lateral
pterygoid and masseter muscle)

The medial pterygoid muscle attaches to the angle of the mandible and to the lateral pterygoid
plate to form a sling with the masseter muscle that suspends the mandible. The primary action is
to elevate the mandible and laterally deviate it to the opposite side.

37
There may be a question about which muscle retrudes the mandible (posterior fibers of the
temporalis muscle)

Actions Muscles

Depression (Open mouth) Lateral pterygoid

Suprahyoid

Infrahyoid

Elevation (Close mouth) Temporalis

Masseter

Medial pterygoid

Protrusion (Protrude chin) Masseter (superficial fibres)

Lateral pterygoid

Medial pterygoid

Retrusion (Retrude chin) Temporalis

Masseter (deep fibres)

Side-to-side movements Temporalis on same side

(grinding and chewing)
Pterygoid muscles of opposite side

Masseter

There may be a question to define endomysium (within the muscle, is a layer of areolar
connective tissue that surrounds each individual muscle cell. It also contains capillaries and
nerves).

38
There may be a question to define the endoneurium (The endoneurium also called endoneurial
channel, endoneurial sheath, endoneurial tube, or Henle's sheath) is a layer of delicate connective
tissue around the myelin sheath of each myelinated nerve fiber. Its component cells are called
endoneurial cells).

There may be a question to define the perineurium (the sheath of connective tissue surrounding
a bundle (fascicle) of nerve fibers within a nerve). Remember if they use the word “neuri” they
are talking about nervous system and if they use the word “mysi” there are talking about
muscle).

There may be a question about which nerve innervates the thenar muscle of thumb (median
nerve)

The following three muscles are considered part of the thenar eminence:

 Abductor pollicis brevis abducts the thumb. This muscle is the most superficial of the
thenar group.

 Flexor pollicis brevis, which lies next to the abductor, will flex the thumb, curling it up in
the palm.

 Opponens pollicis lies deep to abductor pollicis brevis. As its name suggests
it opposes the thumb, bringing it against the fingers. This is a very important movement,
as most of human hand dexterity comes from this action.

There may be a question about which nerve innervates the triceps muscle (radial nerve)

The radial nerve supplies the posterior portion of the upper limb. It innervates the medial and
lateral heads of the triceps brachii muscle of the arm, as well as all 12 muscles in the posterior
osteofascial compartment of the forearm and the associated joints and overlying skin. It
originates from the brachial plexus, carrying fibers from the ventral roots of spinal nerves C5,
C6, C7, C8 & T1. The radial nerve and its branches provide motor innervation to the dorsal arm
muscles (the triceps brachii and the anconeus) and the extrinsic extensors of the wrists and
hands; it also provides cutaneous sensory innervation to most of the back of the hand, except for
the back of the little finger and adjacent half of the ring finger (which are innervated by the ulnar
nerve). The radial nerve divides into a deep branch, which becomes the posterior interosseous
nerve, and a superficial branch, which goes on to innervate the dorsum (back) of the hand.

There may be a question about what brachial nerve & muscle is for circumduction of the
arm? (Axillary nerve and deltoid muscle).

Circumduction at a joint is a motion that circumscribes a cone. The shoulder, being the most
mobile joint in the body, can circumscribe the largest cone. Muscles: pectoralis major,

39
subscapularis, coracobrachialis, biceps brachii, supraspinatus, deltoid, latissimus dorsi, teres
major and minor, infraspinatus, long head of triceps.

There may be a question about what muscle adducts the scapula? (Rhomboids)

Rhomboids, are rhombus-shaped muscles associated with the scapula and are chiefly responsible
for its retraction or depression of the scapula. They are innervated by the dorsal scapular nerve.

There may be a question about the difference of smooth and skeletal muscle (skeletal muscle
uses troponin and smooth muscle uses calmodulin).

There may be a question about which tongue muscle is not innervated by cranial nerve 12
hypoglossal nerve (palatoglossus muscle).

Innervation of the tongue consists of motor fibers, special sensory fibers for taste, and general
sensory fibers for sensation. Motor supply for all intrinsic and extrinsic muscles of the tongue is
supplied by efferent motor nerve fibers from the hypoglossal nerve (CN XII), with the exception
of the palatoglossus. The palatoglossus is innervated by the vagus nerve (CN X)

40
There may be a question about what nerve innervates the true vocal cords (Recurrent laryngeal
branch of the vagus).

The intrinsic laryngeal muscles are described as such because both of their attachments are
within the larynx. The intrinsic muscles include the interarytenoid, lateral cricoarytenoid,
posterior cricoarytenoid, cricothyroid, and thyroarytenoid (true vocal cord) muscles. All of the
intrinsic muscles are paired (that is, there is a right and left muscle) with the exception of the
transverse interarytenoid. All of the intrinsic laryngeal muscles work together to adduct (close)
the vocal cords with the exception of the posterior cricoarytenoid (innervated by the external
laryngeal nerve), which is the only muscle that abducts (opens) the vocal cords.

There may be questions about suprahyoid muscle

The suprahyoid muscles are four muscles located above the hyoid bone in the neck. They are the
digastric, stylohyoid, geniohyoid, and mylohyoid muscles. They are all pharyngeal muscles, with
the exception of the geniohyoid muscle. The digastric is uniquely named for its two bellies. Its
posterior belly rises from the mastoid process of the cranium. The anterior belly arises from the
mastoid notch on the inner surface of the mandibular body. The two bellies connect at the
intermediate tendon. These four muscles have different actions, but in general assist in elevating
the hyoid bone and widening the esophagus during swallowing. When the two bellies of the
digastric contract, they pull upward on the hyoid bone; but if the hyoid is fixed from below, the
digastric assists in extreme opening of the mouth such as yawning or taking a large bite of an
apple. The mylohyoid elevates the hyoid bone, tenses the floor of the mouth. The Geniohyoid
pulls the hyoid bone anterosuperiorly, shortening the floor of the mouth and widening the
pharynx during swallowing. The Stylohyoid elevates and retracts the hyoid bone, elongating the
floor of the mouth during swallowing.

41
Muscle Origin Insertion Innervation

Mylohyoid nerve - branch of

Digastric (anterior Digastric fossa of Intermediate
CN V3 (Mandibular division
belly) Mandible Tendon
of Trigeminal nerve)

Digastric (posterior Intermediate

Mastoid notch Facial nerve
belly) Tendon

Inferior mental
C1 via the hypoglossal nerve
Geniohyoid spine of Symphysis Hyoid
(XII)
menti

Stylohyoid Temporal styloid process Hyoid Facial nerve

Mylohyoid nerve - branch of

Mylohyoid line of
Mylohyoid Hyoid CN V3 (Mandibular division
mandible
of Trigeminal nerve)

Muscle quick review:

 Action potential  Ca released from sarcoplasmic reticulum  binds to troponin on
actin (thin)  tropomyosin moves  myosin (thick) binds  ATP binds myosin,
releasing it from actin  Pi hydrolyzed from ATP  myosin-ADP rebinds actin at
further site  ADP released  repeat

 Muscle spindle [LENGTH]

o Intrafusal fibers  gamma-motor neurons:

 Nuclear bag fibers = dynamic changes  group Ia afferents

 Nuclear chain fibers = static changes  group II afferents + group Ia

afferents

o Monosynaptic  contraction (activates alpha motor neuron) [stretch/myotatic

reflex]

 Golgi tendon organ [TENSION]

42
o Group Ib afferents

o Disynaptic  relaxation (inhibits alpha motor neuron)

43
 Circulatory system
What is the pathway of blood starting at the right atrium: Right atrium ----tricuspid valve --- right
ventricle --- pulmonary valve ---- pulmonary artery (carries deoxygenated blood) ------ lungs -----
pulmonary vein (carries oxygenated blood) ----- left atrium ----- bicuspid (also called mitral valve) ----- left
ventricle -----aortic valve ------ aorta -----arteries ----arterioles ------ capillaries ---- venules ----- veins ------
vena cava (IVC = inferior vena cava brings blood from lower body back to the heart) ------- right atrium ---
-start over from the top

What is the electrical conductivity through the heart? SA node (mainly under sympathetic control, but
is kept from going out of control and beating to fast through the assistance of the parasympathetics) ----
- av node (slowest part of the electrical conduction of the heart) ------- bundle of his ------ purkinje fibers
(fastest part of the heart conduction pathway).

Remember the two areas inside the body: In the blood, or not in the blood. If you have something that
goes inside of the cell, then that means that particular thing is not in the blood. An example would be if
we increase sodium transport into the cell, we are essentially decreasing blood (serum/vascular)
sodium. Do you get it?

What is Hydrostatic pressure? Hydrostatic pressure is a push pressure. Think of this push pressure as
pushing fluid through a membrane in the body. That means in order for the fluid to go through the
membrane it would need to be thin enough, or have holes in it for the fluid to flow. Fluid will tend to
move from areas of low solute concentration to areas of high solute concentration. The word dilution is
the best way to describe this. If you have some concentrated orange juice, you will add water to it to
dilute it. This movement of water from low solute concentration to high solute concentration is called
(Osmosis). Solutes are pretty much anything other than water. Examples of solutes in the body are
proteins (albumin), and other things like glucose, sodium etc…

There may be a question about atherosclerosis and the area affected (tunica intima).

There are three main forms of arteriosclerosis: (1) atherosclerosis, the most common type, in which
plaques of fatty deposits form in the inner layer (tunica intima) of the arteries; (2) Mönckeberg's
arteriosclerosis, called also medial calcific sclerosis because of involvement of the middle layer (tunica
media) of the arteries, where there is destruction of muscle and elastic fibers and formation of calcium
deposits; and (3) arteriolar sclerosis or arteriolosclerosis, which is marked by thickening of the walls of
arterioles. All three forms may be present in the same patient, but in different blood vessels. When
reference is made to hardening of the arteries, this usually refers to atherosclerosis; the terms
arteriosclerosis and atherosclerosis are often used interchangeably.

There may be a question about the similarity between the pulmonary artery and the aorta. (both have
tricuspid semilunar valves).

The atria of the left and right side of the heart are thin-walled, low pressure chambers. Note, the
pulmonary arterial pressure is much lower than in the aorta (systemic arterial pressure). The pulmonary

44
circulation is, overall, a much lower pressure system than is the systemic circulation. The systemic
circulation has to work against gravity, especially when a person is standing, and the system needs more
pressure to do this! Remember that the pulmonary circulation is only as tall as the lungs! The systemic
circulation must also redirect blood according to the needs of the body using smooth muscle; in order to
accomplish this task, the systemic circulation must be capable of generating significant resistance with
smooth muscle. Remember, too, that systemic resistance generated primarily by arterioles is necessary
to generate the high pressures required to drive blood through the high volume, long distance systemic
circulation! The pulmonary circulation, on the other hand, only needs to get blood from the top to the
bottom of the lungs which are perfused by constant low pressure; there is very little redirection of blood
within the pulmonary circulation, other than from locally hypoxic pockets in the lung! Pulmonary
arterioles have much less smooth muscle than systemic arterioles and, thus, pulmonary arterioles
generate much less resistance than systemic arterioles.

What is Osmotic/colloidal/oncotic pressure? This type of pressure is a pull pressure. These types of
pressures will pull fluids toward them. For example, If you have an increased amount of protein in the
tissues, in respect to the amount of proteins you have in the blood. That means the concentration of
solute (proteins) is greater in the tissue. Therefore fluid will move into the tissues causing EDEMA (fluid
in the tissues).

There may be a question about the major protein regulating serum osmolarity (albumin).

Serum albumin is the main protein of human blood plasma. It binds water, cations (such as Ca2+, Na+
and K+), fatty acids, hormones, bilirubin, thyroxine (T4) and pharmaceuticals (including barbiturates): its
main function is to regulate the Oncotic pressure of blood. Alpha-fetoprotein (alpha-fetoglobulin) is a
fetal plasma protein that binds various cations, fatty acids and bilirubin. Vitamin D-binding protein binds
to vitamin D and its metabolites, as well as to fatty acids. The isoelectric point of albumin is 4.9.

Would the following cause edema?

1. Increase capillary hydrostatic pressure? Yes this would cause edema because hydrostatic
means push and you are pushing fluid from the capillaries. If you push it from the capillaries it
will go into the tissues causing edema.
2. Increase tissue colloidal pressure? Yes this would cause edema because you are pulling fluids
into the tissue leading to edema.
3. Decreased vascular Albumin? Yes this would cause edema. Albumin is a proteins, vascular
means blood, therefore all this is saying is that you have decreased protein in the blood. If there
is decreased protein in the blood, this problem means there is more protein in the tissue. If
there is more protein in the tissue, and because proteins are solutes, this means you have a high
tissue solute concentration. Fluids will then go into the tissue due to osmotic pressure causing
edema.

Heart sounds made by the closing of valves: closing of the av valves = 1 st heart sound (lub) and closing
of semilunar valves= 2nd heart sound (Dub)

45
Cardiac Physiology:

 Left side of the heart is higher pressure and higher resistance

o Will always close first

o Always open second

 Mitral Valve/Aortic Valve

 Right side of the heat is under lower pressure

o Will always close 2nd

o Open 1st

 Tricuspid valve/Pulmonary valve

Afterload = the max resistance the L ventricle has to overcome to flow through the aorta

systolic  diastolic 120  80

  100
o Mean arterial pulse pressure = 2 2

Cardiac equations 

Stroke volume = the amount of blood leaving the aorta with each contraction

Cardiac output = the amount of blood that leaves the heart in one minute

Heart rate = the number of heart beats in 1 minute

What is total peripheral resistance: Think of resistance as something that impedes flow. Take a busy
highway for example. If you have 10 lanes and 100 cars, there is no real problem. But if there is an
accident and 9 of the lanes are now closed, leaving only one lane open. What happens to the flow and
pressure of traffic? Decreases flow and increase pressure because of decreased area. The same thing is
true in the circulatory system. The area with the greatest number of vessels, will have the greater flow
and less pressure. Increasing TPR is like decreasing the number of traffic lanes are decreasing the area in
which drivers can drive. Even making the lanes smaller in size can increase the resistance, thus
increasing the pressure.

46
 End Diastolic Voume (EDV)  preload: This is the volume of blood in the ventricle right before it
ejects the blood into the aorta.

 End Systolic Volume (ESV)  This is the volume of blood in the left ventricle after the ventricles
have contracted and right before they begin to fill again during diastole. Remember diastole is
the filling of the heart with blood and systole is the ejection of blood.

o Dobutamine → ↓ contractility and ↓ ESV

 SV how much you actually pumped out = Stroke Volume

 EDV-ESV = SV

o Average SV = 100cc/beat

 Ejection Fraction

SV
EF 
o EDV
 Normal EF 50-80%

 o If trying to increase SV

 Need to increase EDV =

 IV fluids

 Deep breath

 venoconstriciton
when walking

 blood transfusion

 CO= SV x HR

o Ex. Athletes’ heart have more contractility due to hypertrophy and ↓ Total Peripheral
Resistance (TPR) from the formation of new capillaries

 Therefore, Athletes will have ↑ contractility, ↑ ejection fraction, ↑ SV = ↓ HR,

to keep CO the same

 The athlete with the best endurance has the lowest HR

o When SV goes down (dehydrated) need to HR

 Normal CO = 5L/min

47
 CO = SV x HR
 BP = CO x TPR = SV x HR x TPR

 Mean Arterial Pressure – Intracranial pressure = cerebral perfusion pressure

o MAP – ICP = CPP

 ↑ ICP = ↓ CPP

 Ex. hypertension causes a headache because MAP will cause  of ICP by the
same amount to keep CPP the same.

 Cushings reflex = ICP (after MVA) will cause MAP in order to BP and
maintain CPP

 The brain tells the body to do this!!!

 Papilledema → indicates pressure on the brain

Congenital heart disease

These are the most common congenital heart disease

 VSD (Ventral Septal Defect)

 ASD (Atrial Septal Defect)

 PDA (Patent Ductus Arteriosus)

o continuous murmur

o Pulse pressure will decrease

o Mixed venous O2 will 

 Coarctation

o Common in Turner’s syndrome

o Differential pulses

o Differential cyanosis- always associated with PDA

 between up/down and R/L

o Adult type will not have a PDA

48
Cyanotic Heart Disease

 Tetrology of Fallot: PROVe

o Most common cyanotic heart disease AFTER 1 month of age.

 look for Infant or Child

o Remember Cause and Affect

 Pulmonary stenosis

 Right ventricular hypertophy

 Overriding Aorta

 VSD (to shunt blood to the left side)

 Ebstein’s Anomaly

o tricuspid valve is displaced into the R ventricle

 hanging too low, insufficient, swinging back and

forth

Vascular Physiology

Aorta

 Largest vessel in the body

 Has the thickest layer of smooth muscle = stratified squamous cell epithelium on the interior →
Because blood comes out of the Ventricle at high speeds and makes a sharp right

o Therefore, the basement membrane is made for abrasion (like skin)

o Remember that any collagen disease can affect the aorta

49
 The Aorta has the most compliance

Volume
o Compliance=  Pressure

 Will allow to accept a lot of volume without change in Pressure

 Recall that Elastin contains demosin

o Atherosclerosis → artery will lose compliance → systolic HTN → Widened Pulse Pressure

 Arterioles have the most smooth muscle by cross sectional area

 Therefore, can have the most significant influence on BP

 Arterioles have β2 receptors

 Act as stop-cocks b/c they protect

the capillaries

 They try to maintain perfusion

 Capillaries have the thinnest wall → this allows

diffusion fxn (renal capillaries)

o Recall Fick’s Principle

o ↑↑↑ Surface Area

 Veins and Venules

o Have the most capacitance = ↑ ability to hold on to blood

 Hold > 60% of blood at one time.

o Function:

 When a patient is HYPOVOLEMIC the body will squeeze blood from the veins
back into circulation

 Arteries and Veins have α1 receptors

o When someone veno/vasoconstrict → shunt blood away from the SKIN & GI = Skin
turgor and ↓ bowel sounds

o Vessels are usually under Sympathetic control → Vasoconstriction

50
 o Reactive Hyperemia

 Vasodilation of an arteries will occur in the area where there has been damage
to a sympathetic nerve

 If you cut a Parasympathetic nerve the vessel will constrict

o Veins are regulated by the parasympathetic system

o Arteries are regulated by the sympathetic system

 Vessel Pathology

o Hyperplastic arteriosclerosis

 Scarring and bad HTN for at least 6 months → Malignant HTN

 The vessels are trying to hold on

 Onion skinning

o Hyaline atherosclerosis

 Much milder → no scarring involved

 Hyaline deposition

During Systole why is there little blood flow to the coronary?

 Aortic valves open

o The coronary ostia is occluded by aortic valves

o Resistance increases in coronary vessels during systole

Filtration forces: 

 For Filtration

o Hydrostatic pressure (in the vessel)

o Oncotic pressure (protein in the interstitium)

Hint. int
 Against filtration

o Hydrostatic pressure (in the interstitium)

HV V
51
 o oncotic pressure (protein inside the vessel)

  FF= (Hv+ int.)-(Hint+ v)

 HV and πV have the most influence on FF

o Example:

 Explain edema in HF:  hydrostatic pressure in vessel (pooling)

 Explain edema in cirrhosis: liver is not making protein  oncotic pressure in

vessel.

 Venules suck waste product in.

o As blood goes through arteries, oncotic pressure sucks water out of arteries leaving RBC
in the vessels

o That increases osmolarity in the vessel until the blood reaches the venules

o In the Venule the osmolarity will cause water (and waste) to go into the vessel

Flow:

P1  P0
Q
 Flow, R

  R (Resistance) will  flow (Q)

 o Pressure will have to  by the same amount to keep flow (Q) constant

 Any vasculitis will lead to increase BP b/c you ↑ R = ↓ Q

1
R
 Resistance, r4

o As the  radius   Resistance   Flow

  Radius has the largest impact on flow

 Vasoconstrict vs. Vasodilate

 That’s why we have so many mechanisms to control radius

 Q = 1/nL

o n = Viscosity, L = length of tubing

52
  So as Viscosity   flow will    BP to maintain flow

o Example: DIABETES

 diabetes = ↑ glucose in blood = ↑ viscosity = ↓ Q

 In order to return flow → resistance must ↑ to compensate → this will offset

atherosclerosis

 If the heart isn’t enough to compensate pressure will ↑↑

 Therefore, important to keep Glucose under control in order control BP

 Need to keep blood glucose at 126 in the kidneys.

 Diabetics get foot ulcers because they are further away (↑ L), and therefore get
the least amount of flow = “Glove and Stocking” loss of sensation

 Always checks the diabetic’s feet

o Polycythemia will  blood viscosity   BP

 Need to  viscosity by phlebotomy

o A “larger” person will have more tubing   L   Flow  BP to compensate because
the body’s response to vasodilate has been exhausted

 Therefore, Obesity will lead to hypertension

 Poissielle Law

P1  P0 r 4
Q
nL8
o

The most important way to regulate flow is through changing the radius

Circulatory quick review

 Blood = plasma + formed elements (RBCs, WBCs, thrombocytes) // plasma = proteins +
water // serum = plasma - fibrinogen

 AB blood = universal receiver (no antibodies) // O blood = universal donor (no antigens)

 Oxyhemoglobin dissociation curve:

o Shift to the right (LESS affinity // MORE oxygen release) -- {Bohr effect}

 Increased acidity (decreased pH)

53
  Increased CO2

 Increased temp

 Increased 2,3-BPG

 Arteries
o Largest pressure
o High pressure, low compliance
 Arterioles
o Largest resistance  pressure drop
o Regulator of blood flow
 Veins
o Largest blood volume
o Low pressure, high compliance (volume reservoirs)
 Capillaries
o Largest cross-sectional area
 Edema = abnormal leakage of fluid into interstitial spaces // failure of lymphatics to
return fluid
o Excessive capillary fluid filtration (most common cause)
 1) Increased capillary filtration coefficient
 2) Increased capillary hydrostatic pressure
 3) Decreased plasma colloid osmotic pressure
 *Hydrostatic pressure = OUT (filtration) // colloid osmotic pressure = IN
(absorption)
 Baroreceptor = stretch receptors in carotid sinus + aortic arch (high pressure =
parasympathetic // low pressure = sympathetic)
 Chemoreceptor = carotid and aortic bodies (detect increases in CO2, decreases in O2,
decreases in pH)

54
 Respiration

I. The Mechanics of Breathing

A. Relationships of Pressure

1. atmospheric air pressure 760 mm Hg (at sea level)

2. negative air pressure - LESS than 760 mm Hg

3. positive air pressure - MORE than 760 mm Hg

4. intrapleural pressure - pressure within the pleural "balloon" which surrounds the lung

5. intrapulmonary pressure - pressure within the alveoli (tiny sacs) of the lung itself

Factors holding lungs AGAINST the thorax wall:

1. Surface tension holding the "visceral" and "parietal" pleura together

2. Intrapulmonary pressure ALWAYS slightly greater than intrapleural pressure by 4mmHg

3. Atmospheric pressure acting on the lungs

a. atelectasis (collapsed lung) - hole in pleural "balloon" causes equalization of pressure and
collapse of the lung

b. pneumothorax - abnormal air in the intrapleural space, can lead to collapsed lung

Factors facilitating lung movement AWAY from thorax wall:

1. Elasticity of lungs allows them to assume smallest shape for given pressure conditions

2. Fluid film on alveoli allows them to assume smallest shape for given pressure conditions

II. Volume/Pressure & Inspiration/Expiration

A. Boyle's Law on Volume/Pressure Relationships

55
1. Volume is INVERSELY proportional to Pressure

a. INCREASE in Volume -> DECREASE in Pressure

b. DECREASE in Volume -> INCREASE in Pressure

VOLUME change --> PRESSURE change gas flows to equalize the pressure

2. Simple Example of Boyle's Law

- plastic bag with plastic tube in the top

- as bag expands by pulling, gas moves IN

- as bag shrinks by squashing, gas moves OUT

B. Inspiration

1. diaphragm muscle contracts, increasing thoracic cavity size in the superior-inferior

dimension

2. external intercostal muscles contract, expanding lateral & anterior-posterior dimension

3. INCREASED volume (about 0.5 liter)

DECREASED pulmonary pressure (-1 mm Hg) air rushes into lungs to fill alveoli

4. deep/forced inspirations - as during exercise and pulmonary disease

* scalenes, sternocleidomastoid, pectorals are used for more volume expansion of thorax

C. Expiration

1. quiet expiration (exhalation) - simple elasticity of the lungs DECREASES volume

INCREASED pulmonary pressure -> movement of air out of the lungs

2. forced expiration - contraction of abdominal wall muscles (i.e. obliques & transversus
abdominus) further DECREASES volume beyond relaxed point ----> further INCREASE in
pulmonary pressure ---> more air moves out

56
III. Factors Influencing Pulmonary Ventilation

A. Respiratory Passageway Resistance

1. upper respiratory passageways - relatively large, very little resistance to airflow (unless
obstruction such as from food lodging or cancer)

2. lower respiratory passageways - from medium-sized bronchioles on down, can alter

diameter based on autonomic stimulation

a. parasympathetic - causes bronchioconstriction

b. sympathetic - inhibits bronchioconstriction

epinephrine - used to treat life-threatening bronchioconstriction such as during asthma and

anaphylactic shock (carried by people susceptible to sudden constriction)

B. Lung Compliance & Elasticity

1. lung compliance - the ease with which lungs can be expanded by muscle contraction of
thorax

a. fibrosis - decreases compliance

b. blocked bronchi - decreases compliance

c. surface tension - alveoli difficult to expand

d. thorax inflexibility - decreases compliance

2. lung elasticity - the ease with which lungs can contract to their normal resting size
(exhalation) a. emphysema - decreases elasticity

3. alveolar surface tension - liquid on surface of alveoli causes them to collapse to smallest
size

a. surfactant - lipoproteins that reduces surface tension on alveoli, allowing them to expand
more easily. Surfactant is produce by type 2 Pneumocytes.

b. infant respiratory distress syndrome - premature babies that do not yet produce enough
surfactant; must be ventilated for respiration

57
IV. Volumes, Capacities, and Function Tests

1. tidal volume (TV) - normal volume moving in/out (0.5 L)

2. inspiratory reserve volume (IRV) - volume inhaled AFTER normal tidal volume when
asked to take deepest possible breath (2.1-3.2 L)
3. expiratory reserve volume (ERV) - volume exhaled AFTER normal tidal volume when
asked to force out all air possible (1.- 2.0 L)
4. residual volume (RV) - air that remains in lungs even after totally forced exhalation (1.2
L)

B. Respiratory CAPACITIES

1. inspiratory capacity (IC) = TV + IRV (MAXIMUM volume of air that can be

inhaled)
2. functional residual capacity (FRC) ERV + RV (all non-tidal volume expiration)
3. vital capacity (VC) = TV + IRV + ERV (TOTAL volume of air that can be
moved)
4. total lung capacity (TLC) = TV + IRV + ERV + RV (the SUM of all volumes;
about 6.0 L)

D. Dead Space

1. anatomical dead space - all areas where gas exchange does not occur (all but alveoli)

2. alveolar dead space - non-functional alveoli

3. total dead space - anatomical + alveolar

E. Pulmonary Function Tests

1. spirometer - measures volume changes during breathing

a. obstructive pulmonary disease - increased resistance to air flow (bronchitis or asthma)

b. restrictive disorders - decrease in Total Lung Capacity (TB or polio)

58
2. minute respiratory volume (MRV) - total volume flowing in & out in 1 minute (resting
rate = 6 L per minute)

3. forced vital capacity (FVC) - total volume exhaled after forceful exhalation of a deep
breath

4. forced expiratory volume (FEV) - FEV volume measured in 1 second intervals (FEV 1...)

F. Alveolar Retention Rate (AVR)

AVR = breath rate X (TV - dead space)

(NORMAL) AVR = 12/minute X (500 ml – 150 ml)

(NORMAL) AVR = 4.2 L/min

V. Basic Properties of Gases

A. Dalton's Law of Partial Pressures

1. partial pressure - the "part" of the total air pressure caused by one
component of a gas

Gas Percent Partial Pressure (P)

ALL AIR 100.0% 760 mm Hg

Nitrogen 78.6% 597 mm Hg (0.79 X 760)

Oxygen 20.9% l59 mm Hg (0.21 X 760)

Carbon Dioxide 0.04% 0.3 mm Hg (0.0004 X 760)

B. Henry's Law of Gas Diffusion into Liquid

1. Henry's Law - a certain gas will diffuse INTO or OUT OF a liquid down its concentration
gradient in proportion to its partial pressure

2. solubility - the ease with which a certain gas will "dissolve" into a liquid (like blood
plasma)

HIGHest solubility in plasma Carbon Dioxide

Oxygen

59
LOWest solubility in plasma Nitrogen

VI. Gas Exchange: Lungs, Blood, Tissues

A. External Respiration (Air & Lungs)

1. Partial Pressure Gradients & Solubilities

a. Oxygen: alveolar (104 mm) ---> blood (40 mm)

b. Carbon Dioxide: blood (45 mm) ----> alveolar (40 mm) (carbon dioxide much more
soluble than oxygen)

2. Alveolar Membrane Thickness (0.5-1.0 micron)

a. very easy for gas to diffuse across alveoli

b. edema - increases thickness, decreases diffusion

3. Total Alveolar Surface Area for Exchange

a. total surface area healthy lung = 145 sq. Meters

b. emphysema - decreases total alveolar surface area

4. Ventilation-Blood Flow Coupling

a. low Oxygen in alveolus -> vasoconstriction

b. high Oxygen in alveolus -> vasodilation

c. high Carb Diox in alveolus -> dilate bronchioles

d. low Carb Diox in alveolus -> constrict bronchioles

60
B. Internal Respiration (Blood & Tissues)

1. Oxygen: blood (104 mm) -> tissues (40 mm)

2. Carbon Dioxide: tissues (>45 mm) -> blood (40 mm)

VII. Oxygen Transport in Blood: Hemoglobin

A. Association & Dissociation of Oxygen + Hemoglobin

1. oxyhemoglobin (HbO2) - oxygen molecule bound

2. deoxyhemoglobin (HHb) - oxygen unbound

H-Hb + O2 <= === => HbO2 + H+

2. binding gets more efficient as each O2 binds (This is called cooperative

binding and is associated with the sigmoid Oxygen dissociation curve).

61
4. release gets easier as each O2 is released

5. Several factors regulate AFFINITY of O2

a. Partial Pressure of O2

b. temperature

c. blood pH (acidity)

d. concentration of “diphosphoglycerate” (DPG)

The easiest way to think of the oxygen dissociation curve is: “if the tissues need oxygen the
curve will shift to the right”.

2. carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide

VIII. Transport of Carbon Dioxide

A. Dissolved in Blood Plasma (7-10%)

B. Bound to Hemoglobin (20-30%)

1. carbaminohemoglobin - Carb Diox binds to an amino acid on the polypeptide chains

2. Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a. tissues - as Ox is unloaded, affinity for Carb Diox increases

b. lungs - as Ox is loaded, affinity for Carb Diox decreases, allowing it to be released

62
C. Bicarbonate Ion Form in Plasma (60-70%)

1. Carbon Dioxide combines with water to form Bicarbonate

CO2 + H2O <==> H2CO3 <==> H+ + HCO3-

2. carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a. tissues - catalyzes formation of Bicarbonate

b. lungs - catalyzes formation of Carb Diox

3. Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH

(H+ increase), and more unloading of Ox to tissues

a. since hemoglobin "buffers" to H+, the actual pH of blood does not change much

4. Chloride Shift - chloride ions move in opposite direction of the entering/leaving

Bicarbonate, to prevent osmotic problems with RBCs

D. Carbon Dioxide Effects on Blood pH

1. carbonic acid-bicarbonate buffer system

low pH --> HCO3- binds to H+

high pH --> H2CO3 releases H+

2. low shallow breaths --> HIGH Carb Diox --> LOW pH (higher H+)

3. rapid deep breaths --> LOW Carb Diox --> HIGH pH (lower H+)

63
IX. Neural Substrates of Breathing

A. Medulla Respiratory Centers

Inspiratory Center (Dorsal Resp Group - rhythmic breathing) ---->

phrenic nerve ----> innervates the diaphragm (C3,4,5 keeps the diaphragm alive)

intercostal nerves ---->

diaphragm + external intercostals

Expiratory Center (Ventral Resp Group - forced expiration) ---->

phrenic nerve ---->

intercostal nerves ---->

internal intercostals + abdominals (expiration)

1. eupnea - normal resting breath rate (12/minute)

2. drug overdose - causes suppression of Inspiratory Center

B. Pons Respiratory Centers

1. pneumotaxic center - slightly inhibits medulla, causes shorter, shallower, quicker breaths

2. apneustic center - stimulates the medulla, causes longer, deeper, slower breaths

C. Control of Breathing Rate & Depth

1. breathing rate - stimulation/inhibition of medulla

2. breathing depth - activation of inspiration muscles

3. Hering-Breuer Reflex - stretch of visceral pleura that lungs have expanded (vagal nerve)

64
D. Hypothalamic Control - emotion + pain to the medulla

E. Cortex Controls (Voluntary Breathing) - can override medulla as during singing and
talking

X. Chemical Controls of Respiration

A. Chemoreceptors (CO2, O2, H+)

1. central chemoreceptors - located in the medulla

2. peripheral chemoreceptors - large vessels of neck

B. Carbon Dioxide Effects

1. a powerful chemical regulator of breathing by increasing H+ (lowering pH)

a. hypercapnia Carbon Dioxide increases ->

Carbonic Acid increases ->

pH of CSF decreases (higher H+)>

DEPTH & RATE increase (hyperventilation)

b. hypocapnia - abnormally low Carbon Dioxide levels which can be produced by excessive
hyperventilation; breathing into paper bag increases blood Carbon Dioxide levels

C. Oxygen Effects

1. aortic and carotid bodies - oxygen chemoreceptors

2. slight Ox decrease - modulate Carb Diox receptors

3. large Ox decrease - stimulate increase ventilation

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4. hypoxic drive - chronic elevation of Carb Diox (due to disease) causes Oxygen levels to
have greater effect on regulation of breathing

D. pH Effects (H+ ion)

1. acidosis - acid buildup (H+) in blood, leads to increased RATE and DEPTH (lactic acid)

E. Overview of Chemical Effects

Chemical Breathing Effect

increased Carbon Dioxide (more H+) increase

decreased Carbon Dioxide (less H+) decrease

slight decrease in Oxygen effect CO2 system

large decrease in Oxygen increase ventilation

decreased pH (more H+) increase

increased pH (less H+) decrease

Metabolic = Bicarbonate change

Respiratory = Carbon dioxide change

Normal values (pH = 7.4, C02 = 40, HC03= 24)

To determine acid base disturbance look first at the pH. If it is below 7.4 its acidic and above 7.4
its basic (alkaline). The second thing you look at is the bicarbonate (HC03). If it is below 24 it
means acidic and above 24 means basic (alkaline). Third you look at the carbon dioxide. If it is
below 40 it is alkaline and if it is above 40 it is acid.

66
Sample case: Man is hyperventilating and his pH = 8.0, C02 = 20 and HC03 = 28. This would
mean he has a respiratory alkalosis with compensation. We will discuss this more in class
because it can be a bit confusing.

XII. COPD and Cancer

1. Common features of COPD

a. almost all have smoking history

b. dyspnea - chronic "gasping" for air

c. frequent coughing and infections

d. often leads to respiratory failure

2. obstructive emphysema - usually results from smoking

a. enlargement & deterioration of alveoli

b. loss of elasticity of the lungs

c. "barrel chest" from bronchiole opening during inhalation & constriction during
exhalation

3. chronic bronchitis - mucus/inflammation of mucosa

67
 Renal
Renal and Acid-Base Physiology

 Distribution of water:

o Intracellular fluid (ICF) contains 2/3rds of total body water (TBW); major cations
are K+ and Mg+2; major anions are protein and organic phosphates.

o Extracellular fluid (ECF) contains 1/3rd of TBW; composed of interstitial fluid

(ISF) and plasma; major cation is Na+; major anions are Cl- and HCO3-.

 Plasma is ¼ of the ECF and thus 1/12 of TBW; major plasma proteins are
albumin and globulins.

 ISF is ¾ of the ECF and thus ¼ of TBW; composition of ISF is the same
as the plasma except that it has little protein. Therefore, ISF is an
ultrafiltrate of plasma.

 Shifts of water between compartments:

o At steady state, ECF osmolarity and ICF osmolarity are equal. To achieve this
equality, water shifts between the ECF and ICF. It is assumed that solutes such as
NaCl and mannitol do not cross cell membranes and are confined to ECF.

o Changes in volume and osmolarity of body fluids following

 Renal clearance, Renal Blood Flow (RBF) and Glomerular Filtration Rate (GFR):

o Clearance: indicates the volume of plasma cleared of a substance per unit of time.
The units are ml/min and ml/24 hrs.

 C = UV/P where

 C = clearance

 U = urine concentration (mg/ml)

 V = urine volume/time (ml/min)

 P = plasma concentration (mg/ml)

 Vasoconstriction of renal arterioles, which leads to a ↓ RBF, is produced

by activation of the sympathetic nervous system and angiotension II. At

68
 low conc, angiotension II preferentially constricts efferent arterioles,
thereby protecting (increasing) the GFR. ACE inhibitors dilates efferent
arterioles and produce a decrease in GFR which reduces hyperfiltration
and the occurrence of diabetic nephropathy in diabetes mellitus.

 A measurement of renal plasma flow (RPF) can be determined by

measuring clearance of paraaminohippuric acid (PAH), but this estimate
underestimates true RPF by 10% because clearance of RAH does not
measure renal plasma flow to regions of the kidney that do not filter and
secrete PAH.

 Measurement of RBF:

 RBF = RPF/(1 – Hct)

o where 1 – Hct is the fraction of blood volume occupied by

plasma.

 GFR:

 Measurement of GFR by measuring the clearance of inulin, which

is filtered but not reabsorbed or secreted by the renal tubules.

o GRF = ([U]inulin * V) / [P]inulin

 Filtration fraction (FF), which is the fraction of RPF filtered across

the glomerular capillaries (FF = GFR/RPF), and is normally about
.20. Thus, 20% of the RPF is filtered. The remaining 80% leaves
the glomerular capillaries by the efferent arterioles and becomes
the peritubular capillary circulation. Increases in FF produce
increases in the protein concentration of peritubular capillary
blood.

 Determining GFR-Starling forces: The driving force for glomular

filtration is the net ultrafiltration pressure across the glomular
capillaries. Filtration is always favored in glomerular capillaries
because the net ultrafiltration pressure always favors the movement
of fluid out of the capillary.

o Starling equation: GFR = Kf[(Pgc – Pbs) – (πgc – π bs)]

 Kf is the filtration coefficient of the glomerular

capillaries. The glumerular barrier consists of the
capillary endothelium, basement membrane, and

69
 filtration slits of the podocytes. Normally, anionic
glycoproteins line the filtation barrier and restrict
the filtration of plasma proteins, which are neg
changed.

 Pgc is glomerular capillary hydrostatic pressure,

which is constant along length of capillary. It is ↑ed
by dilation of afferent arteriole or constriction of the
efferent arteriole. ↑ Pgc = ↑ net ultrafiltration
pressure and GFR.

 Pbs is Bowman’s space hydrostatic pressure. It is

↑ed by constriction of the ureters. ↑ Pbs = ↓ net
ultrafiltration pressure and GFR.

 Πgc is glomerular capillary oncotic pressure. It

normally increases along the length of the
glomerular capillary because filtration of water
increases the protein conc of glomerular capillary
blood. It is ↑ed by ↑ in [protein]. ↑ in πgc = ↓ in
net ultrafiltration and GFR.

 Πbs is Bowman’s space oncotic pressure. It is

usually zero because only a small amount of protein
is normally filtered.

 Reabsorption and Secretion:

o The reabsorption and secretion rate is the difference between the amount filtered
across the glomerular capillaries and the amount excreted in the urine.

o Transport maximum (Tm) curve for glucose – a reabsorbed substance: Filtered

load of glucose increases in direct proportion to the plasma glucose concentration.

 Reabsorption of glucose: Na+-glucose cotransport in the proximal tubule

reabsorbs glucose from tubular fluid into the blood. There are a limited
number of Na+-glucose carriers, such that at plasma [glucose]:

 < 250 mg/dl - all filtered glucose can be reabsorbed.

 > 350 mg/dl – all carriers are saturated (=Tm); higher levels cannot
result in ↑ reabsorption.

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o Excretion of glucose – threshold is defined as the plasma concentration at which
glucose first appears in the urine (=250 mg/dl).

o Relative clearances of substances:

 Substances with the highest clearance are those that are both filtered
across the glomerular capillaries and secreted from the peritubular
capillaries into urine (e.g. PAH).

 Sunstances with low clearances are those that are either not filtered (e.g.
protein) or are filtered and subsequently reabsorbed into peritubular
capillary blood (e.g. Na+, glucose, AA, HCO-3, Cl-).

 Substances with clearances equal to GFR are glomerular markers and are
those that are freely filtered, but not reabsorbed or secreted (e.g. inulin).

 Relative clearances: PAH>K+>inulin>urea>Na+>glucose, aa, and HCO-3.

o Na+ reabsorption along the nephron:

 Proximal tubule: reabsorbs 67% of the filtered Na+ and H20 and is the site
of glomerulotubular balance. The process is isosmotic (the reabsorption
of Na+ and H20 are exactly proportional).

 Early proximal tubule: reabsorbs Na+ and H20 with HCO3-,

glucose, amino acids, phosphate, and lactate.

o Na+ is reabsorbed by cotransport with glucose, AAs,

phosphate, and lactate. These cotransport processes
account for the reabsorption of all the filtered glucose and
AAs.

o Na+ is also reabsorbed by countertransport via Na+-H+

exchange, which is linked directly to the reabsorption of
filtered HCO-3.

o Carbonic anhydrase inhibitors (e.g. acetazolamide) are

diuretics that act in the early proximal tubule by inhibiting
the reabsorption of filtered HCO3-.

 Middle and late proximal tubules: Na+ is reabsorbed with Cl-.

 Thick ascending limb of the loop of Henle: reabsorbs 25% of the filtered
Na+.

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  It contains a Na+/K+/2Cl- cotransporter in the luminal membrane.

 It is the site of action of the loop diuretics (furosemide, ethacrynic

acid, bumetanide), which inhibit the cotransporter.

 It is impermeable to water. Thus, NaCl is reabsorbed without

water and as a result tubular fluid and tubular osmolarity decrease
to less than their plasma concentrations. This segment, therefore,
is called the diluting segment.

 It has a lumen-positive potential difference.

 Distal tubule and collecting duct: together reabsorb 8% of the filtered Na+

 Early distal tubule reabsorbs NaCl by a Na+/Cl- cotransporter and

is the site of action of thiazide diuretics. It is impermeable to
water, as well, which further dilutes the tubular fluid. It is called
the cortical diluting segment.

 Late distal tubule and collecting duct have two types of cells:

o Principal cells reabsorb Na+ and H2O and secrete K+.

 Aldosterone (steroid hormone, slow to act)

increases Na+ reabsorption and increases K+
secretion.

 ADH increases H2O permeability by directing the

insertion of aquaporins in the luminal membrane.
In the absence of ADH, the principal cells are
virtually impermeable to H2O.

 K+-sparing diuretics (spironoloactone, triamterene,

amiloride) decrease K+ secretion.

o α-Intercalated cells secrete H+ by a H+-ATPase, which is

stimulated by aldosterone and reabsorb K+ by a H+,K+
ATPase.

 K+ regulation:

o Most of the body’s K+ is located in the ICF. A shift of K+ out of cells causes
hyperkalemia, a shift of K+ into cells causes hypokalemia.

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 Renal Regulation of Urea, Phosphate, Calcium and Magnesium

o Urea: 50% of the filtered urea is reabsorbed passively in the proximal tubule. The
distal tubule, cortical collecting ducts, and outer medullary collecting ducts are
impermeable to urea. ADH increases urea permeability in the inner medullary
collecting ducts. Urea reabsorption from inner medullary collecting ducts
contributes to urea recycling in the inner medulla and to the development of the
corticiopapillary osmotic gradient.

o Phosphate: 85% of the filtered phosphate is reabsorbed in the proximal tubule by

Na+/Phos cotransport. The rest (15%) is excreted in the urine. Parathyroid
hormone (PTH) inhibits phosphate reabsorption in the proximal tubule by
activating AC  ↑ cAMP  ↓ Na+/Phos cotransport  causing phosphaturia and
increased urinary cAMP.

 Phosphate is a urinary buffer for H+, excretion of H2PO4- is called

titratable acid.

o Calcium: 60% of the plasma Ca++ is filtered across the glomerular capillaries.
Together the proximal tubule and thick ascending limb reabsorb more than 90%
of the filtered Ca++ by passive processes that are coupled to Na+ reabsorption.

 Loop diuretics cause increased urinary Ca++ excretion. Because Ca++

reabsorption is linked to Na+ reabsorption in the loop of henle, inhibition
of Na+ also inhibits Ca++. If volume is replaced, loop diuretics can be
used in the treatment of hypercalcemia.

 The distal tubule and collecting ducts reabsorb 8% of the filtered Ca++ by
an active process:

 PTH increases Ca++ reab by activating AC in the distal tubule.

 Thiazide diuretics ↑ Ca++ reab in the distal tubule and therefore

decrease Ca+ excretion. Thiazides are used in the treatment of
idiopathic hypercalciuria.

o Magnesium: is reabsorbed in the proximal tubule, thick ascending limb of loop,

and distal tubule. In the thick ascending limb , Mg++ and Ca++ compete for
reabsorption; therefore hypercalcemia causes an increase in Mg++ excretion (by
inhibiting Mg++ reab). Likewise, hypermagnesemia causes an increase in Ca++
excretion (by inhibiting Ca++ reab).

 Concentration and Dilution of Urine:

73
o Concentrated urine is high when circulating ADH levels are high.

o Renin-angiotensin-aldosterone system: is used in long-term blood pressure

regulation by adjustment of blood volume. Renin is an enzyme; angiotensin I is
inactive; angiotensin II is physiologically active; angiotensinase degrades
angiotensin II.

 ↓ in renal profusion pressure causes the juxtaglomerular cells of the

afferent arteriole to secrete renin  renin catalyzes the conversion of
angiotensinogen to angiotensin I in plasma  ACE catalyzes the
conversion of angiotensin I to angiotensin II, primarily in the lungs (ACE
inhibitors block this conversion and therefore ↓ bp)  angiotension II has
two effects:

 1) it acts on the zona glomerulosa of the adrenal cortex to

stimulates the synthesis and secretion of aldosterone. Aldosterone
 ↑ Na+ reab by the renal distal tubule, thereby ↑ing ECF volume,
blood volume, and arterial pressure.

 2) It causes vasoconstriction of the arterioles, thereby ↑ing TPR

and mean arterial pressure.

 Hyperkalemia increases aldosterone secretion, as well. Aldosterone

increases renal K+ secretion, restoring blood [K+] to normal.

 Actions of aldosterone:

 ↑ renal Na+ reab (action on the principal cells of the late distal
tubule and collecting duct).

 ↑ renal K+ secretion (action on the principal cells of the late distal

tubule and collecting duct).

 ↑ renal H+ secretion (action on the α-intercalated cells of the late

distal tubule and collecting duct).

 Hypoaldosteronism: The lack of aldosterone has three direct effects on the

kidney: 1) ↓ Na+ reab 2) ↓ K+ secretion 3) ↓ H+ secretion. As a result,
there is ECF volume contraction caused by ↓ Na+ reab, hyperkalemia
caused by ↓ K+ secretion, and metabolic acidosis caused by ↓ H+
secretion. The ECF volume contraction can cause othrostatic hypotension
and the decreased ECF  ↓ arterial pressure  ↑ pulse rate via
baroreceptor mechanism. ECF volume constration also stimulated ADH
secretion from post pituitary via volume receptors. ADH causes ↑ water

74
 reab from collecting ducts, which results in ↓ serum [Na+] (hyponatremia)
and ↓ serum osmolarity. Thus, ADH released by a volume mechanism is
inappropriate for the serum osmolarity in this case. Hyperpigmentation is
also an associated symptom.

o ADH (vasopressin) is involved in the regulation of blood pressure in response to

hemorrhage, but not in the minute-to-minute regulation of normal bp. Atrial
receptors respond to a decrease in blood volume or pressure and cause the release
of ADH from the posterior pituitary. ADH has two effects that tend to ↑ bp
toward normal: 1) it is a potent vasoconstrictor that ↑TPR by activating V1
receptors on the arterioles. 2) it increases water reabsorption by the renal distal
tubule and collecting ducts by activating V2 receptors

o Atrial natriuretic peptide (ANP) is released from the atria in response to an

increase in atrial pressure. It causes relaxation of vascular smooth muscle,
dilation of the arterioles, and decreased TPR. It causes increased excretion of
Na+ and water by the kidney, which reduces blood volume and attempts ot bring
arterial pressure down to normal. And it inhibits renin secretion.

 Acid-Base Balance

o Acid production: Two types of acid are produced in the body:

 Volatile acid is CO2, which is produced from the aerobic metabolism of

cells. CO2 combines with H2O to form the weak acid H2CO3, which
dissociates into H+ and HCO3-. Carbonic anhydrase, which is present in
most cells, catalyzes the reversible reaction between CO2 and H2O.

 Nonvolatile acids, or fixed acids, include sulfuric acid (a product of

protein catabolism) and phosphoric acid (a product of phospholipids
catabolism). They are produced at a rate of 40-60 mmoles/day. Other
fixed acids that may be overproduced in disease or may be ingested
include ketoacids, lactic acid, and salicylic acid.

o Buffers prevent a change in pH when H+ ions are added to or removed from a

solution. They are most effective within 1 pH until of the pK of the buffer.

 Extracellular buffers: The major one is HCO-3, which had a pK of the

CO2/HCO-3 buffer pair is 6.1. Phosphate is a minor buffer and the pK of
the H2PO4-/HPO4-2 buffer pair is 6.8. Phosphate is most important as a
urinary buffer.

 Intracellular buffers: Organic phosphates and proteins. Of the proteins,

imidazole and α-amino groups on proteins have pKs that are within the

75
 physiologic pH range. Hemoglobin is a mjor intracellular buffer, and in
the physiologic pH range, deoxyhemoglobin is a better buffer than
oxyhemoglobin.

 HH equation to calculate pH: pH = pK + log [A-]/[HA]

 Titration curves describe how the pH of a buffered solution changes as H+

ions are added or removed from it. A buffer is most effective in the linear
portion of the titration curve, where the addition or removal of H+ causes
little change in pH. When the pH of the solution equals the pK, the concs
of HA and A- are equal.

o Renal acid-base:

 Reabsorption of filtered HCO-3 occurs primarily in the proximal tubule.

H+ and HCO-3 are produced in the proximal tubule cells from CO2 and
H2O, which combine to form H2CO3, catalyzed by intracellular carbonic
anhydrase. H2CO3 dissociates into H+ and HCO3-. H+ is secreted into
the lumen via the Na+/H+ exchange mechanism in the luminal membrane.
The HCO-3 is reabsorbed. In the lumen, the secreted H+ combines with
filtered HCO3- to form H2CO3, which dissociates into CO2 and H2O,
catalyzed by brush border carbonic anhydrase. CO2 and H2O diffuse into
the cell to start the cycle again. The process results in a net reabsorption
of filtered HCO3-, but not a net secretion of H+.

 Regulation of reabsorption of filtered HCO-3:

 Increases in the filtered load of HCO-3 result in increased rates of

HCO-3 reabsorption, but the filtered load can exceed the
reabsorptive capacity, and HCO-3 will be excreted in the urine.

 Pco2: Effects of changes in Pco2 are the physiologic basis for the
renal compensation for respiratory acidosis and alkalosis.

o Increases in Pco2 result in increased rates of HCO-3

reabsorption because the supply of intracellular H+ for
secretion is increased.

o Decreases in Pco2 result in decreased rates of HCO-3

reabsorption because the supply of intracellular H+ for
secretion is decreased.

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 Acid-base disorders

 Metabolic acidosis: Overproduction or ingestion of fixed acid or

loss of base produces an increase in arterial [H+] (acidemia).
HCO-3 is used to buffer the extra fixed acid. As a result, the
arterial [HCO-3] decreases, which is the primary disturbance.
Acidemia causes hyperventilation, which is the respiratory
compensation for metabolic acidosis. Renal correction of
metabolic acidosis consists of increased excretion of the excess
fixed H+ as titratable acid and NH4+ and increased reabsorption of
“new” HCO3-, which replenishes the HCO-3 used in the buffering
of the added fixed H+

o In chronic metabolic acidosis, an adaptive increase in NH3

synthesis aids in the excretion of excess H+.

o Serum anion gap = [Na+] – ([Cl-] + [HCO3-]) and

represents unmeasured anions in serum, including
phosphate, citrate, sulfate, and protein. The normal value is
~12 mEq/L. In metabolic acidosis, the serum [HCO-3]
decreases as it is depleted in buffering acid. For
electroneutrality, the conc of another anion must increase to
replace HCO-3. If as a result, the serum anion gap ↑, an
unmeasured anion compensated. If the serum anion gap is
normal, the conc of Cl- is ↑ to compensate (hyperchloremic
metabolic acidosis).

o Diarrhea: Loss of HCO-3 from the GI tract causes a ↓ in the

blood [HCO-3] and a decrease in blood pH via HH
equation and thus metabolic acidosis. To maintain
electroneutrality, the HCO-3 lost from the body is replaced
by Cl-, thus there is a normal anion gap. Hyperventilation
is the respiratory compensation. Diarrhea also causes ECF
volume contraction, which leads to ↓ in blood volume and
arterial pressure. Thus decrease in arterial pressure
activates the baroreceptor reflex, resulting in increased
sympathetic outflow to the heart and blood vessels. A ↑
pulse rate is a consequence of increased sympathetic
activity in the SA node, and pale skin can result from
cutaneous vasoconstriction. ECF volume constriction also
activates the renin-angiotensin-aldosterone system, and ↑
levels of aldosterone lead to increased distal K+ secretion

77
 and hypokalemia. Loss of K+ in diarrhea also contributes
to hypokalemia.

 Treatment consists of replacing all fluid and

electrolytes lost in diarrhea fluid and urine.

Class Site of action Mechanism Major effects

Loop diuretics Thick ascending limb Inhibition of ↑ NaCl excretion

(furosemide, of loop of Henle Na+/K+/2Cl-
ethacrynic acid, cotransporter ↑ K+ excretion
(because of ↑ distal
butetanide)
tubule flow rate)

↑ Ca+ excretion (treat

hypercalcemia)

↓ ability to
concentrate urine (b/c
of ↓ CPOG)

↓ ability to dilute
urine (b/c of
inhibition of diluting
segment)

Thiazide diuretics Early distal tubule Inhibition of NaCl ↑ NaCl excretion

(chlorothiazide, (cortical diluting reabsorption
↑ K+ excretion
hydrochlorothiazide) segment)
(because of ↑ distal
tubule flow rate)

↓ Ca+ excretion (treat

idiopathic
hypercalcemia)

↓ ability to dilute
urine (b/c of
inhibition of cortical
diluting segment)

No effect on ability to
concentrate urine

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Renal quick review

 GFR = 150-250 L/day (120 ml/minute); urine = 1-2 L/day

o Measured by creatinine, BUN, or inulin

 Cortical nephrons = excretory + regulatory functions // juxtamedullary nephrons =

concentrate + dilute urine

 Proximal tubule: reabsorption  ~2/3 of Na and H2O + 100% of glucose and amino
acids

 Loop of Henle

o Descending: permeable to H20

o Ascending: permeable to Na and Cl

 Countercurrent exchange mechanism: Na pumped out of filtrate and into

interstitium  hypertonic interstitium  reabsorption of water from
collecting duct  concentrated urine

 Distal tubule: controlled by aldosterone (reabsorbs Na and excretes K)

 Collecting duct: controlled by ADH (reabsorbs H2O)

 Elevated plasma osmolarity  small volume of concentrated urine

o Causes of concentrated urine: excess ADH // diabetes mellitus // decreased

plasma volume // cellular dehydration

 Decreased plasma osmolarity  large volume of diluted urine

o Causes of dilute urine: absence of ADH // diabetes insipidus

 Renin (kidney)  angiotensinogen (blood)  angiotensin I  angiotensin II (ACE from

lungs)

o Renin secreted due to: sympathetic stimulation, hypotension, or decreased Na

delivery

79
 Endocrine
Endocrine hormone can be either:

Peptide hormone – hydrophilic, means they can’t cross the cell membrane by simple diffusion.
Their receptors are located on the outer cell membrane. Things that can cross the cell membrane
by simple diffusion have to be small, non-polar (hydrophobic) and uncharged. Since our cell
membranes have a phospholipid bilayer that makes the membrane permeable to hydrophobic
substances. If a substance is not hydrophobic (like peptide hormones) it will have to get its
information to the interior of the cell via a second messenger system.

Tyrosine Derivatives – hydrophilic hormones

Steroid hormone - end with the word “one or ol”. They are hydrophobic because they are
derived from cholesterol which is a lipid. Therefore steroid hormones have their receptors on the
inside of the cell because they can cross the cell membrane by simple diffusion. They don’t need
a second messenger.

80
The endocrine system can be thought of as a hierarchy. The hypothalamus would be at the top
controlling the action of others in the path.

Pearls

Think of the hypothalamus as having the actions of controlling things after SEX. After sex a
person might get: (thirsty, hungry and their hormones are being released). Therefore the
hypothalamus is the center for hunger, thirst and hormone production and release.

If you see the word Releasing in the name of the hormone, then you should recognize that the
hormone comes from the hypothalamus (ex. Gonadotropic Releasing Hormone (GNRH) or
Thyrotropic Releasing Hormone (TRH). There are two hormones that don’t have the word
Releasing in them, but they still come from the hypothalamus. They are (Dopamine and
Somatostatin).

Hormones

Anterior Pituitary Hormones (Remember the mnemonic FLAT PIG). The Anterior
Pituitary is also called the Adenohypophysis (vascular connection with the hypothalamus).
Anterior and Adeno both start with the letter “A”

 GNRH (Gonadotropic Releasing Hormone) stimulates Anterior Pituitary to secrete FSH

(Follicle Stimulating Hormone and Leutinizing Hormone). Gonads sound like sex

81
 hormones, because they stimulate FSH (which is responsible for the maturation of egg
and sperm). Also Gonads or GNRH stimulates LH ( which is responsible for production
of estrogen from the ovaries and testosterone from the testis). Testosterone comes from
the LeyDIG cells. Remember that men have to DIG holes, so an easy way to remember
that LeyDig is associated with the male testosterone.

In a normal menstrual cycle, the ovum generally disintegrates or becomes nonviable if it is not
fertilized within four days. Ovulation occurs approximately on the 14th day of the cycle,
Estradiol or estrogen, secreted by the ovary will decrease as the corpus luteum develops, slightly
before ovulation FSH levels decline and slowly rise while LH levels rise dramatically in a spike-
like fashion, LH spike is largely responsible for ovulation.

Which cells produce testosterone? _______________________________

What would happen to Testosterone if the action of 17 alpha-hydroxylase is inhibited?

____________

What hormone is responsible for male secondary sexual characteristics?

______________________

If an otherwise healthy 25 year old female had her ovaries removed, one would NOT expect to
see increased blood levels of? ___________________________

What triggers ovulation to begin? _______________

What hormone maintains the corpus luteum?

Corticotropic Releasing Hormone (CRH) is responsible for stimulating the anterior pituitary to
secrete Adrenocorticotropic Hormone (ACTH). Adreno, should make you think of adrenal gland.
This hormone works on the adrenal cortex of the adrenal gland. Adrenal Medulla is NOT
essential

82
 salt

sugar

sex

The deeper you go the sweeter it gets – First Aid way to remember the layers of the Adrenal
Cortex from the outside to the most inner. (Aldosterone is bitter and Sex is sweet). The layers
follow the mnemonic GFR (this reminds us of the glomerular filtration rate) of the kidney, but
for the adrenal gland, we just remember GFR from outside to most inner.

G – Aldosterone (Mineralcorticoid, because salt is a mineral)

F – Cortisol (glucocorticoid, because it affects glucose)

R – Sex Androgens

Aldosterone – steroid hormone that controls sodium (salt) reabsorption in the blood stream. This
increase blood concentration and water will follow, increasing blood volume and blood pressure.
Remember “AL” is a bitter (salt) man.

Cortisol – is a glucocorticoid that can raise blood glucose levels. Cortisol is typically released
during stressful situations. Cortisol raises blood sugar. If the cortisol is increased too much it can
lead to a condition called Cushings. When you think of Cushing think of cushion or a big round
cushion like person. They will have the round moon face, large abdomen, thin legs, they will
bruise easily. Anything that can increase ACTH levels from the anterior pituitary or increase
CRH levels from the hypothalamus can cause cushings.

Sex Androgens – are steroid hormones for masculinity. When present, women can develop
facial hair and deeper voices. When you think of androgens think of a man named ANDY, that
will make you remember it is related to masculinity.

What area is most likely affected causing Cushings disease? _______________

83
Thyrotropic Releasing Hormone (TRH) – acts on the anterior pituitary to causes the secretion of
Thyroid stimulating hormone (TSH). These hormones regulate our metabolism by causing the
production of thyroid hormones T3 and T4. Iodine is necessary for the production of T3 and T4.
Therefore people who are on a strictly sea salt diet might lack iodine (Normal U.S. table salt has
iodine in it) and make them more prone to developing goiters. They act to increase the basal
metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth
hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as
adrenaline). These hormones also regulate protein, fat, and carbohydrate metabolism.

If you have too much T3 or T4 we call that Hypethroidism. The most common example of
hyperthyroidisim is Graves' disease is an autoimmune disorder, in which the body produces
antibodies to the receptor for thyroid-stimulating hormone (TSH). (Antibodies to thyroglobulin
and to the thyroid hormones T3 and T4 may also be produced.). The patient will be intolerant to
heat, skin is moist and warm, they lose weight and the eyes bulge (exophthalmos).

The thyroid gland also secretes the hormone calcitonin which lowers blood calcium.

What part of thyroid is calcitonin secreted from? _____________________________

Which is the epitome of autoimmune disease? _______________________________

How do you measure human basal energy? __________________________________

In hyperthyroidism does the thyroid grow by hyperplasia or hypertrophy?_____________

What supplies blood to the thyroid gland?_______________________________________

Dopamine – comes from the hypothalamus and inhibits Prolactin. Prolactin is need for milk
production, not milk ejection. Too much dopamine causes schizophrenia and too little dopamine
from the substania nigra of the brain causes parkinsons disease.

What hormone is responsible for parkinsons disease? ______________

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In a patient with Parkinson who you are treating which symptom do you not clinically address?
Slow blinking, bradykinesia or drooling mouth? ________________________________

Somatostatin – found in the hypothalamus and pancreas has an Inhibitory effect on most things.
If you see somatostatin, pick an answer that says inhibit.

GRH (Growth Releasing Hormone) – released from the hypothalamus and works on the
anterior pituitary to secrete Growth Hormone (GH). Too much growth hormone can cause
Gigantism in children and Acromegaly in Adults (Both Acromegaly and Adult start with the
letter “A”).

Posterior Pituitary

Both the posterior pituitary hormones are produced in the hypothalamus, but stored in the
posterior pituitary. We call the posterior pituitary the neurohypophysis because it is connected to
the hypothalamus via neuronal control. The two hormones of the posterior pituitary are: oxytocin
and vasopressin (also called antidiuretic hormone (ADH).

ADH – is responsible for reabsorption of water at the distal collecting ducts. By reabsorbing
water, it increased blood volume by decreasing urine output. This will increase the blood
pressure.

What does ADH do? Helps retention of body water by increasing permeability in collecting duct
and distal tubule

Oxytocin – increases uterine contraction and causes milk ejection.

Parathyroid Hormone (PTH) – comes from the parathyroid gland and is responsible for
increasing blood calcium levels. It does this by stimulating osteoClast activity (Clast = Crack the
bone in half and the calcium spills into the blood). That’s why we say PTH increases blood
calcium.

Which artery supplies parathyroid glands? Superior (off external Carotid) and inferior thyroid
(off of thyrocervical trunk of subclavian artery).

Where does the Inferior parathyroid derive from?

________________________________________

What is the HbA1c test measuring? Three month look into hyperglycemia(diabetes) in a patient.
Normal levels are below 6. When the A1C test is used to diagnose diabetes, an A1C level of 6.5
percent or higher on two separate tests indicates you have diabetes.

Know diabetes- what pancreatic islet cells look like

Cut the infundibulum of the hypothalamus you lose vasopressin

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Cancer of adrenal medulla

If the patient has lack of insulin, which process would increase? lipolysis would increase or
decrease? Would glycolysis increase or decrease

Lady taking exogenous cortisol medication for arthritis pain leads to? decrease plasma ACTH

Hypotension, hyperkalemia lead to secretion of? Aldosterone

Decreased plasma volume and increased oncotic pressure leads to infusion of:
Vasopressin(ADH)

All released from Anterior Pituitary except: Vasopressin and Oxytocin

Growth of the bones and cartilage : somatotropin or somatomedin

Intracellularly, Insulin like factors/hormones are associated with: Tyrosine Kinase

How would you describe Diabetes type 1? _______________________________________

How would the islets cells of someone w/ type 1 diabetes appear? Degenerated

Degeneration to anterior pituitary can cause what? - hypogonadism

Adrenal medulla cancer- pheochromocytoma catecholamines release, secondary hypertension;

neuroendocrine tumor, associated with neurofibromatosis.

What are the endocrine causes of a dry mouth? _____________________________________

Myasthenia gravis –it’s a thymoma

Which is not autoimmune? Choices were myasthenia gravis, sjogrens, SLE or Erythroblastosis
fetalis? _______________

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 Gastrointestinal and Nutrition

Chief Cells – Think of the Indian Chief drinking a Pepsi – (chief cells release pepsinogen. When
pepsinogen comes in contact with acidic environment, such as that with HCL, the pepsinogen is
converted to pepsin. Pep sounds like peptides, because that’s what pepsin breaks down).

G Cells – Release gastrin which lowers the pH of the stomach by stimulating the parietal cells to
secrete HCL (hydrochloric acid) making the stomach more acidic. Too much gastrin release
leads to a condition called Zollinger Ellison syndrome.

Which of the following causes activation of the pyloric pump, relaxation of the pylorus, and
contraction of the lower esophageal sphincter? Gastrin causes activation of the pyloric pump
along with relaxation of the pylorus, and contraction of esophageal sphincter. It is a hormone
released by the antral mucosa of the stomach. Secretin primary function is to stimulate pancreatic
secretion of sodium bicarbonate. Pepsinogen is an inactive proenzyme formed and secreted by
the chief cells of the gastric mucosa. When it comes into contact with hydrochloric acid, it
becomes active enzyme pepsin.

CCK – Cholecystokinin – stimulates the gallbladder to release bile. It causes the pancreas to
release digestive enzymes along with causing the increase of hepatic production of bile. The
purpose of bile is to emulsify or break down fat/lipids.

What acts along with lipase? Bile

What is the major function of serum LDL in transportation? Lipoproteins are compounds
containing both lipids and proteins. Serum LDL or low density lipoproteins are intermediate-
density lipoproteins with a high concentration of cholesterol, moderately high concentration of
phospholipids, and minimal amount of triglycerides. Their primary function is to transport their
lipid components, cholesterol, cholesterol esters, and phospholipids from the liver to the
peripheral tissues

How do Low Density Lipoprotein (LDL) particles get into cells? Low density lipoproteins
(LDL) are large spherical particles made up of a core of esterified cholesterol surrounded by a
lipid bilayer containing protein. It is the primary source of cholesterol for cells outside of the
liver and intestine. LDL are transported into cells by receptor-mediated endocytosis

Ghrelin – is found mainly in the stomach and is released when you are hungry. That means that
ghrelin makes you gain weight. One way to think of ghrelin is grillin (like grilling food). We you
grill food you eat and gain weight, therefore ghrelin causes you to gain wait. While grhrelin is in
the stomach, it acts on the hunger center of the hypothalamus of the brain along with leptin.
Leptin makes you lose weight and is released when you are full.

Hormones of the pancreas – alpha cells (secrete glucagon which increases blood glucose
levels). Beta cells (secrete insulin which lowers blood glucose). Delta cells (secrete somtatostatin

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which inhibits everything). It may not inhibit everything, but if you see somatostatin on the test
and they ask for answer regarding its action or function, you would be safe to put “decreases
something” (example would be decrease HCL, decrease pancreas and gallbladder secretion,
decrease insulin and glucagon).

What nerve innervates the ascending colon? Parasympathetic innervation to the ascending
colon is supplied by the vagus nerve. Sympathetic innervation is supplied by the thoracic
splanchnic nerves.

Where is the esophagus located? In humans, the esophagus generally starts around the level of
the sixth cervical vertebra (C6) behind the cricoid cartilage, enters the diaphragm at about the
level of the tenth thoracic vertebra (T10), and ends at the cardia of the stomach, at the level of
the eleventh thoracic vertebra.

Where can you find squamous metaplasia (ABC)? Common sites for squamous metaplasia
include the bladder and cervix. Smokers normally have this in their airways. It is normally
benign due to irritation or Vitamin A deficiency. You may also find a columnar type
squamous metaplasia in Barrett’s esophagus.

What is a common cause of esophageal varices? They are most often a consequence of portal
hypertension, commonly due to cirrhosis. The most common result of the varices is bleeding or
hematemesis.

What is Peutz-Jeghers syndrome? (Putz the Polyps on the lips, mouth, GI tract) Also known
as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease
characterized by the development of benign hamartomatous polyps in the gastrointestinal tract
and hyperpigmented macules on the lips and oral mucosa (melanosis).

What is the dominant factor controlling absorption of iron from the gastrointestinal tract?
The correct choice is saturation of the mucosal cells with iron. Most iron absorption occurs at the
proximal small intestine. Iron first binds to a receptor on the brush border membrane and then
gets transported into the cell. The iron may then be transported to the blood, complexing with
transferrin, while some binds to apoferritin in the cell to form ferritin. With time some of the iron
in ferritin is converted to free iron and transported to the blood. However, much is lost upon
sloughing of the cells. Other major electrolytes absorbed from the small intestine are sodium,
potassium and chloride. Sodium is absorbed via passive diffusion, cotransport, or secondary
active transport and cotransport with chloride ion.

What is the number 1 bacterial cause of a peptic ulcer? Helicobacter Pylori is the main
bacterial cause. Ulcers are typically the result of a low pH/increased acid in the stomach with a
decrease in the protective mucous barrier.

How do you differentiate between a gastric ulcer and duodenal ulcer?

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Gastric = Greater pain with food

Duodenal – Decrease pain with food

Glut Receptors:

Glut 1 – What is the number 1 think you need in your body to live? That’s right BLOOD. Glut 1
is for RBC (red BLOOD cells and the BLOOD brain barrier). Number 1 is the smallest so it
must be for the fetal tissue.

Glut 2 – Think second letter of the alphabet “B” means Beta cells of the pancreas. Also think
about us having 2 kidneys (also found in small intestine). Glut-2 are also associate with
membranes and remember we have a phospholipid Bi-layer. That Bi means 2.

Glut-3 – Think of a 3 year old running around getting on your nerves (neurons), but you still
love (affinity) them alot. Glut-3 mainly found in neurons and has a higher affinity for glucose
than glut-1,2, or 4.

Glut-4 – Think of 2 arms and 2 legs where you find muscle (skeletal muscle) and fat (adipose).
2+2 =4. You find Glut-4 on the skeletal muscles and adipose cells.

The hormone responsible for decreasing gluconeogenesis in the liver is synthesized where?
In humans, insulin is the hormone that promotes fuel storage by decreasing gluconeogenesis in
the liver, promoting glycogen deposition in the liver, and decreasing blood glucose levels.
Insulin is synthesized in the beta cells in the islets of Langerhans in the pancreas. The release
of insulin from the beta cells is stimulated by an increase in the concentration of glucose in the
blood. The action of insulin is antagonized by the hormones produced by the other answer
choices. The adrenal cortex (choice A) is responsible for the production of cortisol. Both
epinephrine and norepinephrine are produced in the adrenal medulla (choice B). Glucagon is
synthesized in the alpha cells in the pancreas (choice C). The anterior lobe of the pituitary
(choice D) is responsible for the production of growth hormone.

MINERALS/VITAMINS

 Fat soluble
o Vitamin A -active form = retinoids (like rhodopsin); -carotene; night
vision; squamous metaplasia
o Vitamin D - active form = calcitriol; Rickets/osteomalacia; most toxic
o Vitamin E - antioxidant; scavenger of free radicals; least toxic
o Vitamin K - synthesis of clotting factors II (prothrombin), VII, IX, X;
deficiency is most common in newborns

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 Water soluble
o Vitamin C (ascorbic acid) - essential for bone matrix, cartilage, &
dentin; Scurvy  affects CT (hydroxylation of lysine & proline in
collagen)
o Thiamin (B1) - Beriberi = deficiency; Wernick-Korsakoff syndrome =
alcoholic deficiency (delirium, ataxia, paralysis of eye muscles,
retrograde amnesia)
o Riboflavin (B2) - FMN and FAD; cheilosis + glossitis + dermatitis
o Niacin (B3) - NAD, NADP; Pellegra  diarrhea, dermatitis, dementia
o Folate - active form = tetrahydrofolate (THF); synthesis of purines
and thymine (DNA synthesis); megaloblastic anemia; most common
deficiency in the US; supplements recommended for prevention of
neural tube defects
o B12 (cobalamin) - absorption requires intrinsic factor from parietal
cells; megaloblastic anemia (pernicious anemia)
o Pantothenic acid - building block of CoA and fatty acid synthase
complex; deficiency is very rare
o Biotin - prosthetic group of ATP-dependent carboxylases; egg white
avidin prevents intestinal absorption
o B6 (pyridoxine) - amino acid metabolism; precursor for pyridoxal
phosphate (PLP); cheilosis + glossitis + anemia
 Vitamins A, C, D = required for normal production of enamel and dentin [A
affects enamel more; C affects dentin more]

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