● PHYSIO COMPREHENSIVE EXAM POINTERS

I. GENERALITIES (7)
▪ Ionic composition of ECF vs. ICF
ECF ICF
(Extracellular Fluid) (Intracellular fluid)
● Fluid ​between spaces​ of ● Fluid ​inside ​the cell
the cell ● 2/3 of body’s water
● 1/3 of body’s water ● K​+​, Mg​2+​, PO​4​2-
● Na​+​, Cl​-​, HCO​3-​, O​2​, Glucose,
Fatty Acids, Amino Acids,
CO​2

ECF
● Fluid between the spaces of cell
● Contains 1/3 of body’s water
● “internal environment” or the ​milieu intérieur
● The extracellular fluid contains large amounts of sodium,
chloride, and bicarbonate ions plus nutrients for the cells,
such as oxygen, glucose, fatty acids, and amino acids.
● It also contains carbon dioxide that is being transported from
the cells to the lungs to be excreted, plus other cellular waste
products that are being transported to the kidneys for
excretion. (Guyton p3)

​ ICF
1. Fluid inside the cell
2. Contains 2/3 of body’s water
The intracellular fluid differs significantly from the extracellular
fluid; for example, it contains large amounts of potassium,
magnesium, and phosphate ions instead of the sodium and chloride
ions found in the extracellular fluid. Special mechanisms for
transporting ions through the cell membranes maintain the ion
concentration differences between the extracellular and intracellular
fluids. (Guyton p4)

▪
▪
▪ Negative feedback vs. positive feedback mechanism
Negative Feedback Mechanism Positive Feedback
Mechanism
● Goal: wnormalize levels ● Can sometimes cause
(e.g. regulation of carbon vicious cycles and death
dioxide concentration) (e.g. hemorrhage)
● Maintains homeostasis ● Can be useful (e.g. blood
● Nature of most control clotting, labor)
systems ● Initiating stimulus causes
more of the same

- Negative Feedback Nature of Most Control Systems​ (Guyton

p7)
- Goal is to normalize levels
- Maintains ​homeostasis​ (metabolic acidosis, metabolic
alkalosis)
- in general, if some factor becomes excessive or deficient, a
control system initiates negative feedback, which consists of
a series of changes that return the factor toward a certain
mean value, thus maintaining homeostasis.

For regulation of carbon dioxide concentration, as

discussed, a high concentration of carbon dioxide in the
extracellular fluid increases pulmonary ventilation, which
decreases carbon dioxide concentration, moving it toward
normal levels. This mechanism is an example of negative
feedback; that is, any stimulus that attempts to change the
carbon dioxide concentration is counteracted by a response
that is negative to the initiating stimulus.
Therefore, in general, if some factor becomes excessive or
​ hich
deficient, a control system initiates ​negative feedback,w
consists of a series of changes that return the factor toward a
certain mean value, thus maintaining homeostasis.

-
-
-
-
 - Positive Feedback ​(Guyton p8)
- Can sometimes cause ​Vicious Cycles​ and death
(hemorrhage)
- Can be ​Useful​ (blood clotting; labor; generation of nerve
signals)
- The initiating stimulus causes more of the same, which is
positive feedback

A system that exhibits positive feedback responds to a

perturbation with changes that amplify the perturbation and
therefore leads to instability rather than stability. For example,
severe hemorrhage may lower blood pressure to such a low
level that blood flow to the heart is insufficient to maintain
normal cardiac pumping; as a result, blood pressure falls even
lower, further diminishing blood flow to the heart and causing
still more weakness of the heart. Each cycle of this feedback
leads to more of the same, which is a positive feedback or a
vicious cycle.
Blood clotting is an example of a valuable use of positive
feedback. When a blood vessel is ruptured and a clot begins to
form, multiple enzymes called ​clotting factors ​are activated
within the clot. Childbirth is another instance in which positive
feed-back is valuable. When uterine contractions become
strong enough for the baby’s head to begin pushing through
the cervix, stretching of the cervix sends signals through the
uterine muscle back to the body of the uterus, causing even
more powerful contractions.

▪ Cellular organelles and their function

Cell ● Impedes Penetration by Water-Soluble
Membrane Substances.
Lipid Barrier ● It is composed almost entirely of proteins
and lipids
● Approximate composition:
○ proteins 55%
○ phospholipid 25%
○ cholesterol13%
○ other lipids 4%
 ○ carbohydrates 3%
● The basic lipid bilayer is three main types
of lipids:
○ phospholipids
○ sphingolipids
○ cholesterol
● Cell/Plasma membrane envelopes the
cell
● Lipid Barrier of the Cell Membrane
Impedes Water Penetration
● The lipid layer in the middle of the
membrane is impermeable to the usual
water-soluble substances, such as ions,
glucose, and urea. Conversely,
fat-soluble substances, such as oxygen,
carbon dioxide, and alcohol, can
penetrate this portion of the membrane
with ease.
Endoplasmic ● Synthesizes Multiple Substances in the
Reticulum Cell
● provides an extensive surface area for the
manufacture of many substances used
inside the cells and released from some
cells
● helps process molecules made by the cell
and transports them to their specific
● The Synthesis of Most Cell Structures
Begins in the ER
○ The granular ER, characterized by large
numbers of ribosomes attached to the
outer surface, is the site of protein
formation.
○ Agranular reticulum functions (no
ribosome attached) for the synthesis
of lipid substances and for other
processes of the cells promoted by
intrareticular enzymes
Golgi ● Functions in Association With the ER
Apparatus ○ transported substances are then
processed in the Golgi apparatus to
form lysosomes, secretory vesicles, and
other cytoplasmic components
● The Golgi Apparatus Processes Substances
Formed in the ER
○ substances entrapped in the ER
vesicles are transported from the
endoplasmic reticulum to the Golgi
apparatus.
○ Packaging and post translation
modification of proteins
Lysosomes ● provides an intracellular digestive system
that allows the cell to digest:
(1) damaged cellular structures
(2) food particles that have been ingested
by the cell, and
(3) unwanted matter such as bacteria
Peroxisomes ● oxidases rather than hydrolases
● oxidases are capable of combining oxygen
with hydrogen ions derived from different
intracellular chemicals to form hydrogen
peroxide (H​2​O​2​)
Secretory ● form of storage vesicles called secretory
Vesicles vesicles or secretory granules
● stores protein proenzymes (enzymes that
are not yet activated)
Mitochondria ● powerhouse of the cell
● release energy in the cell
● self-replicative
Cell Filamentous or Tubulin structures
Cytoskeleton ● is used in all cells to construct strong
tubular structures, the ​microtubules (​ can
 transport substances from one area of
the cell to another)
● structures is to act as a ​cytoskeleton,
providing rigid physical structures
Nucleus ● is the control center of the cell and
contains large amounts of DNA, Also called
genes
● also called the nuclear envelope, separates
Nuclear the nucleus from the cytoplasm.
membrane
Nucleoli ● contain large amounts of RNA and
proteins of the type found in ribosomes.

▪ Different processes of transport of substances through the

cell membranes
Diffusion
- means random movement of molecules either through
intermolecular spaces in the cell membrane or in
combination with a carrier protein. The energy that causes
diffusion is the energy of the normal kinetic motion of
matter.

Simple​ ​diffusion
- means that molecules move through a membrane without
binding to carrier proteins.
- can occur by way of two pathways:
(1) through the interstices of the lipid bilayer, and
(2) through water-filled protein channels that span
the cell membrane.
- is the only form of transport that is not carrier mediated.
- occurs down an electrochemical gradient (“downhill”).
- does not require metabolic energy and therefore is passive.
 - Small hydrophobic solutes (e.g., O​2​, CO​2​) have the highest
permeabilities in lipid membranes.
- Hydrophilic solutes (e.g., Na​+​, K​+​) must cross cell
membranes through water-filled channels, or pores, or via
transporters. If the solute is an ion (is charged), then its flux
will depend on both the concentration difference and the
potential difference across the membrane.

Facilitated diffusion
- requires a carrier protein. The carrier protein aids in
passage of molecules through the membrane, probably by
binding chemically with them and shuttling them through
the membrane in this form.
- occurs down an electrochemical gradient (“downhill”),
similar to simple diffusion.
- does not require metabolic energy and therefore is passive.
- is more rapid than simple diffusion.
- is carrier mediated and therefore exhibits stereospecificity,
saturation, and competition.
- example of facilitated diffusion = Glucose transport in
muscle and adipose cells is “downhill,” is carrier-mediated,
and is inhibited by sugars such as galactose; therefore, it
is categorized as facilitated diffusion.

Active transport
● means movement of substances across the membrane in
combination with a carrier protein and also against an
electrochemical gradient. This process requires a source of
energy in addition to kinetic energy.
●
●
●
●
● 2 types of Active Transport:
■ Primary active transport: the energy is derived
directly from the ​breakdown of adenosine
triphosphate (ATP)​ or some other high-energy
phosphate compound.
- occurs against an electrochemical gradient
(“uphill”).
- requires direct input of metabolic energy in the
form of adenosine triphosphate (aTP) and therefore
is active.
- is carrier mediated and therefore exhibits
stereospecificity, saturation, and competition.
- examples of primary active transport
a. na+, K+-aTPase (or na+–K+ pump)
B. Ca2+-aTPase (or Ca2+ pump)
c. H+, K+-aTPase (or proton pump)
■ Secondary active transport: The energy is derived
secondarily from energy that has been stored in the
form of ​ionic concentration differences​ between the
two sides of a membrane, originally created by
primary active transport. The sodium electrochemical
gradient drives most secondary active transport
processes.
● 2 types of Secondary Active transport:
○ Co-transport​. ​The diffusion energy of
sodium can pull other substances along
with the sodium (in the same direction)
through the cell membrane using a special
carrier protein.
○ Counter-transport. ​The sodium ion and
substance to be counter-transported
move to opposite sides of the membrane,
with sodium always moving to the cell
 interior. Here again, a protein carrier is
required.
​ ​ Secondary active transport
- The transport of two or more solutes is coupled.
- One of the solutes (usually Na+) is transported
“downhill” and provides energy for the “uphill”
transport of the other solute(s).
- Metabolic energy is not provided directly but
indirectly from the Na​+​ gradient that is maintained
across cell membranes.
- If the solutes move in the ​same direction​ across the
cell membrane, it is called ​cotransport/symport​.
(Examples are Na​+​-Glucose cotransport in the small
intestine and renal early proximal tubule and
Na​+​–K​+​–2Cl​–​ cotransport in the renal thick ascending
limb)
- If the solutes move in ​opposite directions​ across
the cell membranes, it is called
countertransport/exchange/antiport​. (Examples are
Na​+​-Ca​2+​ exchange and Na​+​–H​+​ exchange)

▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪ Factors that affect net rate of diffusion

Factors that affect net rate of diffusion

1. Cell membrane permeability
The permeability of a membrane for a given substance is
expressed as the net rate of diffusion of the substance
through each unit area of the membrane for a unit
concentration difference between the two sides of the
membrane (when there are no electrical or pressure
differences).
Permeability is affected by:
● Thickness of membrane
● Lipid solubility
● Temperature
● Size of molecule
2. Concentration gradient​ (substance diffuse from higher
concentration to lower concentration)
The rate of net diffusion through a cell membrane is
proportional to the difference in concentration of the
diffusing substance on the two sides of the membrane.
3. Electrical potential gradient​ (substance diffuse when they
are attracted towards the opposite charge and stop until
charge become neutral)
If an electrical potential is applied across a membrane, the
ions move through the membrane because of their electrical
charges. When large amounts of ions have moved through
the membrane, a concentration difference of the same ions
develops in the direction opposite to the electrical potential
difference. When the concentration difference rises to a
sufficiently high level, the two effects balance each other,
creating a state of electrochemical equilibrium. The
electrical difference that balances a given concentration
difference can be calculated using the Nernst equation.
 4. Pressure gradient​ (substance diffuse from high pressure
side to low pressure side)

▪ Resting membrane potential and contribution of the ions to

the RMP

Potassium diffusion potential: −94 mV

A high ratio of potassium ions from inside to outside the cell, 35:1,
produces a Nernst potential of −94 millivolts according to the
Nernst equation.

Sodium diffusion potential: +61 mV

The ratio of sodium ions from inside to outside the membrane is
0.1, which yields a calculated Nernst potential of +61 millivolts.

Membrane permeability: −86 mV

The permeability of the nerve fiber membrane to potassium is
about 100 times greater compared with sodium, so the diffusion
of potassium contributes far more to the membrane potential.
This high value of potassium permeability in the Goldman
equation yields an internal membrane potential of −86 millivolts,
which is close to the potassium diffusion potential of −94
millivolts.

Electrogenic nature of the sodium-potassium (Na​+​- K​+​) pump:

3Na​+​- 2K​+
The Na​+​-K​+ pump transports three sodium ions to the outside of
the cell for each two potassium ions pumped to the inside, which
causes a continual loss of positive charges from inside the
membrane. Therefore, the Na​+​-K​+ pump is electrogenic because it
produces a net deficit of positive ions inside the cell, which causes
a negative charge of about −4 millivolts inside the cell membrane.
 Resting membrane potential and contribution of the ions to
the RMP

Resting membrane potential

- is expressed as the measured potential difference across the cell
membrane in millivolts (mV).
- is, by convention, expressed as the intracellular potential relative
to the extracellular potential. Thus, a resting membrane potential
of −70 mV means 70 mV, cell negative.
- The resting membrane potential is established by diffusion
potentials that result from concentration differences of permeant
ions.
- each permeable ion attempts to drive the membrane potential
toward its equilibrium potential.
- Ions with the highest permeabilities, or conductances, will make
the greatest contributions to the resting membrane potential, and
those with the lowest permeabilities will make little or no
contribution.
- The na+–K+ pump contributes only indirectly to the resting
membrane potential by maintaining, across the cell membrane,
the Na+ and K+ concentration gradients that then produce
diffusion potentials. The direct electrogenic contribution of the
pump (3 Na+ pumped out of the cell for every 2 K+ pumped into
the cell) is small.

▪
▪
▪
▪
▪
▪
▪
▪
▪
▪
▪ Action potential stages and the role of ions
The successive stages of the action potential are as follows:

• ​Resting stage.
- This is the resting membrane potential before the action
potential occurs. The conductance for potassium ions is
about 100 times as great as the conductance for sodium
ions. This is caused by much greater leakage of potassium
ions than sodium ions through the leak channels.

• ​Depolarization stage.
- At this time, the membrane suddenly becomes permeable to
sodium ions, allowing tremendous numbers of positively
charged sodium ions to move to the interior of the axon.
This movement of sodium ions causes the membrane
potential to rise rapidly in the positive direction.

•​ Repolarization stage.
- Within a few ten-thousandths of a second after the
membrane becomes highly permeable to sodium ions, the
voltage-gated sodium channels begin to close and the
voltage-gated potassium channels begin to open. Then rapid
diffusion of potassium ions to the exterior re-establishes the
normal negative resting membrane potential.

Action potential stages and the role of ions

1. RESTING STATE
- both sodium and potassium channels are closed (voltage gated
channels)

2. THRESHOLD
- stimulus open some Na+ channels
- If threshold is achieved (-50mV), more Na+ are opened
triggering an action potential
3. DEPOLARIZATION
- Na+ channels are open but K+ channels remain closed
- Na+ ion rush into the interior of the cell making it more positive
(less negative)

4. REPOLARIZATION
- Na+ channels close, K+ open
- K+ ion leave the cell
- Inside of cell becomes more negative

5. UNDERSHOOT
- K+ channel remain open
- The cell becomes hyperpolarized (membrane potential falls
below normal resting potential)
II. RESPIRATION (8)

● Muscles of Respiration
First Method: Downward & Upward movement of the
Diaphragm
✦ ​DIAPHRAGM
- the primary muscle used in respiration;
- used in ​Normal quiet breathing wherein during inspiration,
contraction of the diaphragm increases thoracic volume
causing lung expansion. During expiration, the diaphragm
relaxes and the elastic recoils of the lungs, chest wall and
abdominal structures compresses the lungs.

✦ ​ABDOMINAL MUSCLES
- contraction of this muscle group is used during ​Heavy
breathing where extra force is needed to push the
abdominal contents upward against the diaphragm.

Second Method: Raising & Lowering of the Rib Cage

✦ MUSCLES THAT RAISE THE RIB CAGE DURING INSPIRATION
​EXTERNAL INTERCOSTAL MUSCLES - causes the ribs to move
upward & forward in a “bucket handle” motion’
​ Accessory muscles include:
Sternocleidomastoid ​- lifts the sternum
A​nterior Serratus - lifts the ribs directly anterior to the
scapula
Scaleni​ - lifts the first two ribs

✦ MUSCLES THAT PULLS THE RIB CAGE DOWNWARD DURING

EXPIRATION
RECTUS ABDOMINIS MUSCLES - pulls the lower ribs
downward while compressing the abdominal contents
upward against the diaphragm
INTERNAL INTERCOSTAL MUSCLES - ​depresses the rib cage
upon expiration and decreases the space in the pleural
cavity.

●
●
 ● Lung Compliance
- The extent to which the lungs will expand for each unit
increase in ​transpulmonary pressure (if enough time is
allowed to reach equilibrium)
* transpulmonary pressure - the pressure difference
between the alveolar and pleural pressures

- 200 mL of air per centimeter of water ​is the average total

compliance of both lungs of a normal human adult.

- Compliance depends on the following:

⬩ ​Elastic forces of lung tissues - determined by elastin &
collagen fibers
⬩ ​Elastic forces by surface tension - ⅔ in the alveoli of normal
lungs

● Air Volumes and Capacities

Spirometry - ​records changes in most pulmonary volumes and

capacities.

✦ ​Total Pulmonary Volume = Maximum Volume to which the

Lungs can expand

-
-
-
 - The 4 Pulmonary Volumes​:
1. Tidal Volume ​(VT) - volume of air inspired & expired in
normal breathing. (about 500mL)
2. Inspiratory Reserve Volume (IRV) - extra air that can be
inspired over and above the normal ​inh ​ alation (about
3000mL)
3. Expiratory Reserve Volume (ERV) - extra air that can be
inspired over and above the normal ​ex​halation (about
1100mL)
4. Residual Volume (RV) - the volume of air the remained in
the lungs after forceful expiration ( about 1200mL)

✦ ​Pulmonary Capacities - ​combination of 2 or more Pulmonary

Volumes

- Description of 4 Pulmonary Capacities:

1. Inspirational Capacity (IC) - amount of air forcefully
inhaled after a normal expiratory level and distended in
the lungs at maximum time (about 3500mL).
IC = VT + IRV

2. Functional Residual Volum​e (FRV) - amount of air that

remains in the lungs at the end of normal expiration
(about 2300mL).
FRC = ERV + RV

3. Vital Capacity (VC) - maximum amount of air a person

can expel from the lungs after inhaling, then exhaling to
the maximum extent (about 4600mL).
VC = IRV + VT

4. Total Lung Capacity (TLC) - is the maximum volume to

which the lungs can be expanded with the greatest
inspiratory effort (about 5800mL).
TLC = VC + RV

●
 ● Control of Respiration
- The ​rate of alveolar ventilation is regulated by the nervous
system to maintain the arterial blood oxygen (P02 and
PCO2) at constant levels under variety of conditions.

- RESPIRATORY CENTER:
⬩ ​Medulla (medulla oblongata) - the primary respiratory
control center
⬩ ​Pons​ - controls the rate of ​involuntary respiration
⬩ ​Cerebral Cortex - (motor cortex) controls the ​voluntary
respiration

- Hering-Breuer Reflex - ​initiated by the nerve receptors in

the bronchi & bronchioles, triggered to prevent
over-inflation of the lungs and signals respiratory center to
initiate expiration. Mechanism of action is called
Hering-Breuer inflation reflex.

- Excess ​CO​2 or hydrogen ions mainly ​stimulates the

respiration.
- O​2 acts on chemoreceptors in carotid & aortic bodies to
send signals to the respiratory center to ​control respiration.
-
3 Main NEURAL GROUPS in the RESPIRATORY CENTER
Dorsal Respiratory Pneumotaxic Center Ventral Respiratory
Group Group
✶​Location​: Distal portion ✶​Location​: Superior ✶​Location​:
of Medulla portion of Pons Ventrolateral part of
✶​Input​: Chemoreceptors ✶​Input​: Activated Medulla
via the Vagus & when expiration ✶Can cause either
Glossopharyngeal Nerve becomes an active expiration or
✶​Output​: Distal portion process (ex: exercise) inspiration,
of Medulla to ✶​Output​: Transmits depending which
Diaphragm via the inhibitory signals to neural group is
Phrenic nerve dorsal respiratory stimulated
✶​Actions: group and control the ✶Inactive during
- Primary responsible “filling phase” of normal quiet
for inhalation respiration breathing
 - Generates basic ✶​Actions: ✶Stimulates
rhythm for breathing - Limits inspiration Abdominal Expiratory
- Regulates Muscles when higher
inspiratory volume and level of respiration is
respiratory rate required

● Pulmonary Thromboembolism
- is the blockage of an artery in the lungs by an abnormal clot
or ​thrombus that developed in the blood vessels that got
dislodged now called an ​embolus​.
- it is ​not a disease but a complication of underlying venous
thrombosis
- Pulmonary emboli usually arise from the thrombi that
originate in the deep venous system of lower extremities.

- Causes of thromboembolic conditions in humans:

⬩ ​Roughened endothelial surface of a blood vessel (by
arteriosclerosis, infection or trauma) that is most likely to
initiate clotting
⬩ ​Sluggish blood flow that may cause concentration of
procoagulant factors to initiate clotting.

- Signs & Symptoms:

⬩ ​Abrupt onset of pleuritic chest pain
⬩ Shortness of breath
⬩ Hypoxia

●
●
●
●
●
●
●
●
●
●
● Variations in the Different Lung Zones
✦ Zones of Pulmonary Blood Flow
⬩ ​Zone 1 (Top of the Lungs): ​No blood flow during all
portions of cardiac cycle because in this area,
capillary pressure never rises higher than the
alveolar pressure
Alveolar pressure > Artery pressure > Venous
pressure​ thus capillaries are pressed flat

⬩ ​Zone 2 (Middle of the Lungs): Determined bt the difference

between arterial and alveolar pressure.o
Intermittent blood flow during systole
(Arterial pressure > Alveolar
pressure)
No blood flow during diastole (​ Arterial
pressure < Alveolar pressure)
⬩ ​Zone 3 (Bottom of the Lungs): ​Has a high continuous blood
flow because the capillary pressure remains greater
than the alveolar pressure during both systole and
diastole.
 ● Carbon Monoxide Poisoning
- when carbon monoxide builds up in your bloodstream.
- Carbon monoxide combines with hemoglobin on the same
point where oxygen should bind, therefore ​displacing the
oxygen.
- Carbon monoxide binds 250 times as much as the tenacity
of oxygen thus hemoglobin cannot anymore carry oxygen
- Treatment:
⬩ ​Patients with severe carbon monoxide poisoning can be
helped by ​administration of pure oxygen because at high
alveolar pressure, oxygen can displace the carbon monoxide
in the hemoglobin.

● Pulmonary Blood Flow

III.
CARDIOVASCULAR SYSTEM (17)
● Difference in action potential generation of the heart muscle
fiber from SA node
● Ventricles, Atria & the Purkinje System
○ Stable resting membrane ​potential (~-90mV) that
approaches the K​+ ​equilibrium
○ Action potentials are of ​long duration​, especially in
Purkinje fibers (300 msec).
● Sinoatrial (SA) Node
○ Normally the ​pacemaker​ of the heart
○ Unstable resting potential
○ Exhibits automaticity
○ Maybe overriden by AV node and His-Purkinje (latent
pacemakers) when suppressed
○ Intrinsic rate of phase 4 depolarization (and HR) is
fastest in SA node and slowest in the His- Purkinje
system:
SA Node> AV Node> His- Purkinje

PHASES Ventricles, Atria & SA Node

the Purkinje
System
Phase 0:​ ​Upstroke - caused by a - caused by ↑​Ca​2+
of the action transient conductance: influx
potential ↑ Na​+​ conductance: of ​Ca​2+ ​that drives
influx of ​Na​+ membrane
current potential toward
depolarizing the Ca​2+​ equilibrium
membrane potential.
- peak of action
potential:
membrane
potential
approaches Na​+
equilibrium
potential
-upstroke of the
 action potential in
the AV node is the
result of an ​inward
Ca+ current
(as in the SA node)

Phase 1: Initial - Outward current: Absent

Repolarization K​+​ outflux
(brief) (chemical gradient
and electrical
gradient favored)
and ​↓Na​+
conductance (or
influx)
Phase 2: Plateau of -Transient ​↑ Ca​2+ Absent
action potential ​ K​
influx​ and ↑ +

conductance
(outflux)
-outward and
inward currents are
approximately
equal, thus
membrane
potential is stable @
a plateau level
Phase 3: -↓Ca​2+ -​↑K​+​ conductance
Repolarization conductance -thus ​K+​​ outward
(influx) current​ (I​K​) causing
-↑K​+​ conductance
repolarization
(outflux) ​&
predominates
-thus large​ K​+
outward current
(I​K​) ​&
hyperpolarization
 Phase 4: Resting -inward and -​this accounts for
membrane outward currents pacemaker activity
potential (slow (I​K​)​ are equal of SA node
-membrane (automaticity)
depolarization for
approaches ​K+​ -​↑ Na​+
SA node) equilibrium conductance
potential - thus inward ​ Na​+
current ​(I​f​)
-(I​f​)​ turned on by
repolarization
during preceding
action potential

● Cardiac cycle events

The events that occur at the beginning of a heartbeat and last until
the beginning of the next heartbeat are called the ​cardiac cycle.

● Each beat of the heart begins with a spontaneous action

potential that is initiated in the sinus node of the right
atrium near the opening of the superior vena cava.
● The action potential travels through both atria and the A-V
node and bundle into the ventricles.
● A delay of more than 1/10 of a second occurs in the A-V
node and bundle, which allows the atria to contract before
the ventricles contract.

The Atria function as ​primer pumps for the ventricles. The

ventricles ​fill ​with blood during ​diastole ​and ​contract during
systole.
● The​ P wave​ is caused by spread of depolarization across the
atria, which causes atrial contraction.
Atrial pressure increases just after the P wave.
● The​ QRS​ waves appear as a result of ventricular
depolarization about 0.16 second after the onset of the P
wave, and this initiates ventricular contraction; then the
ventricular pressure begins to increase.
 ● The​ ventricular T wave​ is caused by repolarization of the
ventricle.
● The​ a wave​, which is caused by atrial contraction
● The ​c wave,​ which occurs during ventricular contraction
because of slight backflow of blood and bulging of the A-V
valves toward the atria
● The​ v wave,​ which is caused by in-filling of the atria from
the venous return.

● Volume-Pressure curve events

 The volume-pressure work of the heart ​is the work done to
increase the pressure of the blood; in the left heart, it equals stroke
volume multiplied by the difference between the left ventricular mean
ejection pressure and the left ventricular mean input pressure. The
volume-pressure work of the right ventricle is only about one sixth that
of the left ventricle because the ejection pressure of the right ventricle is
much lower.

The volume-pressure diagram of the ​Left Ventricle determines

the ​cardiac work output​. . The phases of the cardiac cycle include the
following:
• ​Phase I​: Period of filling during which the left ventricular
volume increases from the end-systolic volume to the
end-diastolic volume, or from 45 mL to 115 mL, an increase of 70
mL.
• Phase II​: Period of ​isovolumic contraction during which the
volume of the ventricle remains at the end-diastolic volume but
the intraventricular pressure increases to the level of the aortic
diastolic pressure, or 80 mm Hg.
• ​Phase III​: Period of ejection during which the systolic pressure
increases further because of additional ventricular contraction,
and the ventricular volume decreases by 70 mL, which is the
stroke volume.
• ​Phase IV​: Period of isovolumic relaxation during which the
ventricular volume remains at 45 mL, but the intraventricular
pressure decreases to its diastolic pressure level.

●
●
●
●
●
●
●
●
●
●
●
●
● Concepts of preload & afterload (Frank-Starling Mechanism)

● Cardiac work are affected by the preload and afterload on

the heart. ​Preload is usually considered to be the
end-diastolic pressure​, and the ​afterload is considered to
be the ​pressure in the artery exiting the ventricle (aorta
or pulmonary artery).

● When venous return of blood increases, the heart muscle

stretches more, which makes it pump with a greater force of
contraction. The Frank- Starling mechanism of the heart
can be stated in another way: Within physiological limits,
the heart pumps all the blood that comes to it without
allowing excess accumulation of blood in the veins. The
extra stretch of the cardiac muscle during increased venous
return, within limits, causes the actin and myosin filaments
to interdigitate at a more optimal length for force
generation.

● Specialized excitatory and conductive system of the heart

o Sinus node​ (or the sinoatrial node), which initiates the
cardiac impulse
o Internodal pathway,​ which conducts impulses from the
sinus node to the atrioventricular (A-V) node
o A-V node, ​which delays impulses from the atria to the
ventricles
o A-V bundle, ​which delays impulses and conducts impulses
from the A-V node to the ventricles
o Right and left​ bundles of Purkinje fibers,​ which conduct
impulses to all parts of the ventricles.

● Components of the ECG waveform

● P wave
-represents atrial depolarization.
-does not include atrial repolarization, which is “buried” in
the QRS complex.
 ●
●
●
● PR interval
-is the interval from the beginning of the P wave to the
beginning of the Q wave (initial depolarization of the
ventricle).
-depends on conduction velocity through the
atrioventricular (av) node. For
example, if AV nodal
conduction decreases (as in
heart block), the PR interval
increases.
-is decreased by stimulation of
the sympathetic nervous
system.
-is increased by stimulation of
the parasympathetic nervous
system.
● QRS complex
-represents depolarization of the ventricles
● ​QT interval
- is the interval from the beginning of the Q wave to the end
of the T wave.
-represents the entire period of depolarization and
repolarization of the ventricles.
● ST segment
-iis the segment from the end of the S wave to the beginning
of the T wave.
- is isoelectric.
represents the period when the ventricles are depolarized
● T wave
- represents ventricular repolarization

●
●
●
●
●
 ●
●
●
● Analyzing lead groups in ECG reading

3 Bipolar Limb Leads:

1. Lead I - negative terminal of the
electrocardiograph is
connected to the right arm
and the positive terminal is
connected to the left arm.
- Therefore, when the point
where the right arm
connects to the chest is
electronegative with
respect to the point where
the left arm connects, the
ECG records positively, that
is, above the zero-voltage
line in the ECG.

2. Lead II - the negative terminal of the

electrocardiograph is
connected to the right arm
and the positive terminal is
connected to the left leg.
- Therefore, when the right
arm is negative with respect
to the left leg, the
electrocardiograph records
positively
3. Lead III - the negative terminal of the
electrocardiograph is
connected to the left arm
and the positive terminal is
connected to the left leg.
 - This configuration means
that the electrocardiograph
records positively when the
left arm is negative with
respect to the left leg.
Chest Leads (Precordial Leads) - known as leads V1, V2, V3,
V4, V5, and V6 are
connected to the positive
terminal of the
electrocardiograph, and the
indifferent electrode, or the
negative electrode, is
simultaneously connected
to the left arm, left leg, and
right arm
Augmented Unipolar Limb - two of the limbs are
Leads connected through
electrical resistances to the
negative terminal of the
electrocardiograph, and the
third limb is connected to
the positive terminal.

● Computing heart rate from an ECG

-​The rate of paper (i.e. of recording of the EKG) is 25 mV/s which
results in:

● 1 mm = 0.04 sec (or each individual block)

● 5 mm = 0.2 sec (or between 2 dark vertical lines)
● Distance between Tick marks = 3 seconds (in the
rhythm strip)
- The voltage recorded from the leads is also standardized on
the paper where 1 mm = 1 mV (or between each individual
block vertically) This results in:
● 1 mm = 0.1 mV
● 5 mm = 0.5 mV (or between 2 dark horizontal lines)
 ● 10 mm = 1.0 mV
-
-
- Heart rate calculation:
- 1. If it is 1 big box (0.2 secs) then the rate is 60/0.2 =
300 bpm. The rest of the sequence would be as follows.
- 1 big box = 300 beats/min (duration = 0.2 sec)
- 2 big boxes = 150 beats/min (duration = 0.4 sec)
- 3 big boxes = 100 beats/min (duration = 0.6 sec)
- 4 big boxes = 75 beats/min (duration = 0.8 sec)
- 5 big boxes = 60 beats/min (duration = 1.0 sec)
- 2. Count the number of RR intervals between two Tick
marks (6 seconds) in the rhythm strip and multiply by
10 to get the bpm. This method is more effective when
the rhythm is irregular.
- Normal range at rest is between 60-100 beats per minute
(bpm).

● Basic arrhythmias on ECG tracing

● Accelerated Idioventricular Rhythm

The EKG rhythm will appear regular with heart rate that is
50-120 bpm. The P wave features: absent. Observe that the PR
interval is not measurable. The QRS complex will typically be wide
(>0.10 sec), bizarre looking. .
● Accelerated Junctional Rhythm

The EKG rhythm will appear regular with heart rate that is
normal (60-100 bpm). The P wave features: present before,
during (hidden) or after qrs, if visible it is inverted. Observe
that the PR interval is not measurable. The QRS complex
will typically be normal (0.06-0.10 sec). .
●
●
●
●
●
● Asystole

The EKG rhythm will appear not present with heart rate
that is absent. The P wave features: absent. Observe that the
PR interval is absent. The QRS complex will typically be
absent. confirm with multiple leads.
● Atrial Fibrillation

The EKG rhythm will appear irregular with heart rate that is
very fast (> 350 bpm) for atrial, but ventricular rate may be
slow, normal or fast. The P wave features: absent - erratic
waves are present. Observe that the PR interval is absent.
The QRS complex will typically be normal but may be
widened if there are conduction delays. .
● Atrial Flutter

The EKG rhythm will appear regular or irregular with heart

rate that is fast (250-350 bpm) for atrial, but ventricular
rate is often slower. The P wave features: not observable,
but saw-toothed flutter waves are present. Observe that the
PR interval is not measurable. The QRS complex will
typically be normal (0.06-0.10 sec). .
● Bundle Branch Block

The EKG rhythm will appear regular with heart rate that is
the underlying rate. The P wave features: normal. Observe
 that the PR interval is normal (0.12-0.20 sec). The QRS
complex will typically be wide (>0.12 sec). .
●
● First Degree Heart Block

The EKG rhythm will appear regular with heart rate that is
the underlying rate. The P wave features: normal. Observe
that the PR interval is prolonged (>0.20 sec). The QRS
complex will typically be normal (0.06-0.10 sec). a first
degree av block occurs when electrical impulses moving
through the atrioventricular (av) node are delayed (but not
blocked). first degree indicates slowed conduction without
missed beats.
● Second Degree Heart Block Type I

The EKG rhythm will appear irregular but with

progressively longer pr interval lengthening with heart rate
that is the underlying rate. The P wave features: normal.
Observe that the PR interval is progressively longer until a
qrs complex is missed, then cycle repeats. The QRS complex
will typically be normal (0.06-0.10 sec).
● Second Degree Heart Block Type II

The EKG rhythm will appear regular (atrial) and irregular

(ventricular) with heart rate that is characterized by atrial
rate usually faster than ventricular rate (usually slow). The
P wave features: normal form, but more p waves than qrs
complexes. Observe that the PR interval is normal or
prolonged. The QRS complex will typically be normal or
wide. .
●
●
●
●
● Sinoatrial Block

The EKG rhythm will appear irregular when sa block occurs

with heart rate that is normal or slow. The P wave features:
normal. Observe that the PR interval isnormal (0.12-0.20
sec). The QRS complex will typically be normal (0.06-0.10
sec). pause time is an integer multiple of the p-p interval try
to identify specific type of atrial tachycardia - see other
pages.
● Sinus Arrest

The EKG rhythm will appear irregular due to pause with

heart rate that is normal to slow. The P wave
features:normal. Observe that the PR interval is normal
(0.12-0.20 sec). The QRS complex will typically be normal
(0.06-0.10 sec). pause time is not an integer multiple of the
p-p interval.
● Sinus Arrhythmia

The EKG rhythm will appear irregular, varying with

respiration with heart rate that is normal (60-100 bpm) and
rate may increase during inspiration. The P wave features:
normal. Observe that the PR interval is normal (0.12-0.20
sec). The QRS complex will typically be normal (0.06-0.10
sec).heart rate frequently increases with inspiration,
decreasing with expiration.
● Sinus Bradycardia
 The EKG rhythm will appear regular with heart rate that is
slow (< 60 bpm). The P wave features: normal. Observe that
the PR interval is normal (0.12-0.20 sec). The QRS complex
will typically be normal (0.06-0.10 sec). .
● Sinus Tachycardia

The EKG rhythm will appear regular with heart rate that is
fast (> 100 bpm). The P wave features: normal, may merge
with t wave at very fast rates. Observe that the PR interval is
normal (0.12-0.20 sec). The QRS complex will typically be
normal (0.06-0.10 sec). qt interval shortens with increasing
heart rate.
● Third Degree Heart Block

The EKG rhythm will appear regular, but atrial and

ventricular rhythms are independent with heart rate that
is characterized by atrial rate usually normal and faster
than ventricular rate. The P wave features: normal shape
and size, may appear within qrs complexes. Observe that
the PR interval is absent: the atria and ventricles beat
independently.. The QRS complex will typically be normal,
but wide if junctional escape focus. .
● Ventricular Fibrillation

The EKG rhythm will appear highly irregular with heart rate
that is unmeasurable. The P wave features:absent. Observe
that the PR interval is not measurable. The QRS complex
will typically be none. ekg tracings is a wavy line.
●
●
●
● Ventricular Tachycardia

The EKG rhythm will appear regular with heart rate that is
fast (100-250 bpm). The P wave features: absent. Observe
that the PR interval is not measurable. The QRS complex
will typically be wide (>0.10 sec), bizarre appearance. .
● Junctional Tachycardia

The EKG rhythm will appear regular with heart rate that is
fast (100-180 bpm). The P wave features: present before,
during (hidden) or after qrs, if visible it is inverted. Observe
that the PR interval is absent or short. The QRS complex will
typically be normal (0.06-0.10 sec). .
● Multifocal Atrial Tachycardia

The EKG rhythm will appear irregular with heart rate that is
fast (> 100 bpm). The P wave features: often changing shape
and size from beat to beat (at least three differing forms).
Observe that the PR interval is variable. The QRS complex
will typically be normal (0.06-0.10 sec). t wave is often
distorted also review wandering atrial pacemaker lesson.
● Normal Sinus Rhythm

The EKG rhythm will appear regular with heart rate that is
normal (60-100 bpm). The P wave features:normal
(positive & precedes each qrs). Observe that the PR interval
 is normal (0.12-0.20 sec). The QRS complex will typically be
normal (0.06-0.10 sec). .
●
● Premature Atrial Complex

The EKG rhythm will appear irregular with heart rate that
ususually normal but depends on underlying rhythm. The P
wave features: premature, positive and shape is abnormal.
Observe that the PR interval is normal or longer. The QRS
complex will typically be 0.10 sec or less. .
● Premature Junctional Complex

The EKG rhythm will appear regular with premature beats

with heart rate that is the underlying rate. The P wave
features: present before, during (hidden) or after qrs, if
visible it is inverted. Observe that the PR interval is absent
or short. The QRS complex will typically be normal
(0.06-0.10 sec). .
● Premature Ventricular Complex

The EKG rhythm will appear irregular with heart rate that is
the underlying rate. The P wave features: absent. Observe
that the PR interval is not measurable. The QRS complex
will typically be wide (> 0.10 sec), bizarre appearance.two
pvcs together are termed a couplet while three pvcs in a
row with a fast rhythm is ventricular tachycardia.
●

●
●
 ●
●
● Comparison of the different physical characteristics of the
divisions of the circulation

Physical Characteristics of the Circulation

pulmonary circulation - ​which supplies the lungs

systemic circulation - ​which supplies tissues in the remainder of
the body

Functional Parts the Circulation

• ​arteries - which transport blood under high pressure to the
tissues
- have strong vascular walls and rapid blood flow.
• ​arterioles - which are the last small branches of the arterial
system
- act as control valves through which blood is released
into the capillaries.
• ​capillaries - which exchange fluids, nutrients, and other
substances between the blood and
the interstitial fluid.
-They have thin walls and are highly permeable to
small molecules.
• ​venules - which collect blood from the capillaries and gradually
coalesce into progressively larger veins.

Most of the Blood Volume Is Distributed in the Veins of the

Systemic Circulation

84% - total blood volume in the systemic circulation

● 64% - in the veins
● 13% - arteries
● 7% - systemic arterioles and capillaries
7% - blood volume in the heart
9% - pulmonary vessels

Velocity of Blood Flow Is Inversely Proportional to the Vascular

Cross-Sectional Area
Vessels with large cross-sectional area have slower blood flow
velocity

Vessel Cross Sectional

Area (cm2)
Aorta 2.5
Small arteries 20
Arterioles 40
Capillaries 2500
Venules 250
Small veins 80
Venae cavae 8 8

Pressures Vary in the Different Parts of the Circulation

systolic pressure - ​aortic arterial pressure rises to its highest

point
diastolic pressure​ - falls to its lowest during diastole
120/80 mm hg - normal
pulse pressure - difference between systolic and diastolic
pressure (120-80= 40 mm hg )
0 mm hg -as it reaches the termination of the venae cavae in the
right atrium of the heart
35 mm Hg - 10 mm hg - Pressure in the systemic capillaries varies
near the arteriolar ends to near the venous ends
17 mm hg - average functional capillary pressure
 Pressures in the Pulmonary Circulation Are Much Lower
Than Those in the Systemic Circulation

25 mm hg - ​systolic arterial pressure

8 mm hg​ - diastolic pressure
16 mm hg​ - mean pulmonary artery pressure
8 mm hg​- average pulmonary capillary pressure

NOTE:
total blood flow through the lungs is
the same as that in the systemic circulation because of the
lower vascular resistance of the pulmonary blood vessels.

● Ohm’s Law, Poiseuille’s Law and Reynold’s number

o Ohm’s Law
ΔP Arterial Pressure
F = --------- Cardiac output =
-----------------------------------
R Total Peripheral
Resistance

o Poiseuille’s Law:​ gives factors that change the resistance of

blood vessels
π ΔPr4
F = ------------
8ηl

● Rate of flow (F) is directly proportional to radius of

the vessel to the fourth power (r4)
● Rate of flow (F) is indirectly proportional to the
viscosity of the blood (η) and length of vessel (l)

o Reynold’s number:​ predicts whether blood flow will be

laminar (streamlined) or turbulent (if turbulent, causes
audible vibrations called ​bruits​)
▪ ↓blood viscosity (e.g. ↓hematocrit, anemia)
▪ ↑blood velocity (e.g. narrowing of a vessel)
● Factors affecting pulse pressure
o Two major factors affect the pulse pressure:
▪ 1) Stroke volume output of the heart
▪ 2) Compliance (total distensibility) of the arterial tree.
▪ A third, less important factor is the character of
ejection from the heart during systole.

● Blood pressure measurement by the auscultatory method

o

● Clinical estimation of venous pressure

o Venous pressure often can be estimated by simply
observing the degree of distention of the peripheral
veins—especially of the neck veins.. For instance, in the
sitting position, the neck veins are never distended in the
normal quietly resting person.However, when the right
atrial pressure becomes increased to as much as +10 mm
Hg, the lower veins of the neck begins to protrude, and at
+15 mm Hg atrial pressure,essentially all the veins in the
neck become distended.

● Reflex mechanisms for maintaining normal arterial pressure

o

● Renin-Angiotensin-Aldosterone System in controlling arterial

pressure
 o

● Fluid Filtration Across Capillaries as Determined by

Hydrostatic and Colloid Osmotic Pressures

● Effect of total peripheral resistance to long-term cardiac

output

● Effect of changes in external cardiac pressure on the cardiac

output curve

●
●
●
●
●
● Heart Sounds (phonocardiogram)

“lub, dub, lub, dub- normal heart sound

a.) The “lub” sound - It is called the first heart sound and it is
associated with closure of the atrioventricular (A-V) valves at the
beginning of systole. The cause is vibration of the taut valves
immediately after closure, along with vibration of the adjacent
walls of the major vessels around the heart and has a duration
about 0.14 second

b.) The “dub” sound – It is called the second heart sound because
the normal pumping cycle of the heart is considered to start when
the A-V valves close at the onset of ventricular systole. The second
heart sound results from sudden closure of the semilunar valves
at the end of systole. The vibrations occurring in the arterial walls
are then transmitted mainly along the arteries. The vibrations of
the vessels come into contact with a “sounding board,” such as the
chest wall, they create sound that can be heard and has a duration
about 0.11 second

c.) The Third Heart Sound​- A weak rumbling third heart sound is
heard at the beginning of the middle third of diastole. Explanation
of this sound is oscillation of blood back and forth between the
walls of the ventricles initiated by in rushing blood from the atria.
- present in children, adolescents, and young adults and occurs in
older adults having systolic heart failure

d.) ​Atrial Heart Sound (Fourth Heart Sound)-​sometimes be

recorded in the phonocardiogram and almost never be heard with
a stethoscope because of its weakness and very low frequency.
Usually 20 cycles/sec or less and occurs when the atria contract
caused by the inrush of blood into the ventricles which initiate
vibrations similar to those of the third heart sound.
● Heart murmurs caused by valvular lesions

A. Systolic Murmur of Aortic Stenosis

-blood is ejected from the left ventricle through the aortic valve
because of the resistance to ejection, the blood pressure in the left
ventricle rises as high as 300 mm Hg, while the pressure in the
aorta is still normal.

- the turbulent blood impinging against the aortic walls causes

intense vibration, and a loud murmur occurs during systole and
transmitted throughout the superior thoracic aorta and large
arteries of the neck.
-the sound is harsh and in persons with severe stenosis may be so
loud that it can be heard several feet away from the patient.

- sound vibrations can be felt with the hand on the upper chest
and lower neck, a phenomenon known as a ​thril
B. ​Diastolic Murmur of Aortic Regurgitation

-​no abnormal sound is heard during systole, but during diastole,

blood flows backward from the high pressure aorta into the left
ventricle, causing a “blowing” murmur of relatively high pitch
with a swishing quality heard over the left ventricle.
-this murmur results from turbulence of blood jetting backward
into the blood already in the low pressure diastolic left ventricle.

C. Systolic Murmur of Mitral Regurgitation

-blood flows backward through the mitral valve into the left
atrium during systole.
-this backward flow also causes a high-frequency “blowing,”
swishing sound similar
to that of aortic regurgitation but occurring during systole rather
than diastole.
-transmitted into the left atrium. However, the left atrium is so
deep
within the chest that it is difficult to hear this sound directly over
the atrium. As a result, the sound of mitral regurgitation is
transmitted to the chest wall through the left ventricle to the apex
of the heart.

D. Diastolic Murmur of Mitral Stenosis

- blood passes with difficulty through the stenosed mitral valve
from the left atrium into the left ventricle, and because the
pressure in the left atrium seldom rises above 30 mm Hg, a large
pressure differential forcing blood from the left atrium into the
left ventricle does not develop.
- the abnormal sounds heard are usually weak and very low
frequency
-During the early part of diastole, a left ventricle with a stenotic
mitral valve has so little blood in it and its walls are so flabby that
blood does not reverberate back and forth between the walls of
the ventricle.
 ● Stages of shock
1. Nonprogressive stage (compensated stage): can recover
without outside therapy due to circulatory compensatory
mechanisms

*Negative feedback control- cause a person to recover from

moderate degrees of shock

Include the following:

1. Baroreceptor reflexes​- powerful sympathetic stimulation
of the circulation
2. ​CNS ischemic response​- elicits even more powerful
sympathetic stimulation throughout the body but is not activated
until the arterial pressure falls below 50 mm Hg
3. ​Reverse stress relaxation of the circulatory system​- causes
the blood vessels to contract around the diminished blood
volume so that the blood volume that is available more adequately
fills the circulation
4. ​Increased secretion of renin and angiotensin II -constricts
the
peripheral arterioles and causes decreased output of water and
salt.
5. ​Increased secretion by the posterior pituitary gland of
ADH​- constricts the peripheral arterioles and veins and increases
water retention
6. ​Increased secretion of epinephrine and norepinephrine​-
constricts the
peripheral arterioles and veins and increases heart rate
7. ​Compensatory mechanisms​- return the blood volume back
toward normal

2. Progressive stage:​ leads to death without therapy

*Cardiac Depression
 -When the arterial pressure falls low enough, coronary blood flow
decreases.It weakens the heart muscle and thereby decreases the
cardiac output more.
3. Irreversible stage:​ leads to death even with therapy

-Depletion of Cellular High-Energy Phosphate Reserves in

Irreversible Shock
-liver and the heart- are greatly diminished in severe shock

IV. DIGESTIVE SYSTEM(9)

● Hormones that control gastrointestinal motility and
secretion
Another Table From Guyton:

Hormone Stimuli for Site of Actions

Secretion Secretion
Secretin Acid S cells of the Stimulates
Fat duodenum, pepsin
jejunum, secretion,
ileum pancreatic
bicarbonate
secretion,
biliary
bicarbonate
secretion,
growth of
exocrine
pancreas
Inhibits
gastric acid
secretion
Gastrin Protein G cells of the Stimulates
Distention antrum, gastric acid
Nerve duodenum secretion,
(Acid inhibits and jejunum mucosal
release) growth
Cholecystokini Protein I cells of the Stimulates
n Fat duodenum, pancreatic
Acid jejunum and enzyme
ileum secretion,
pancreatic
bicarbonate
secretion,
gallbladder
contraction,gr
 owth of
exocrine
pancreas,Inhi
bits gastric
emptying
Glucose-depen Protein K cells of the Stimulates
dent Fat duodenum insulin release
insulinotropic Carbohydrate and jejunum Inhibits
peptide gastric acid
secretion
Motilin Fat M cells of the Stimulates
Acid duodenum gastric
Nerve and jejunum motility,
intestinal
motility

● Slow waves vs. spike potentials

Electrical Activity of Gastrointestinal Smooth Muscle (p. 797​)

The Rhythm of Most Gastrointestinal Contractions Is Determined by

the Frequency of Slow Waves in the Smooth Muscle Membrane
Potential.
These waves are not action potentials; rather, they are slow,
undulating changes in the resting membrane potential. The cause
of slow waves is poorly understood, but they may result from
slow undulation of the activity of the sodium-potassium pump or
rhythmical changes in sodium permeability.

Spike Potentials Are True Action Potentials That Cause Muscle

Contraction.
Spike potentials occur when the resting membrane potential
becomes more positive
than about −40 millivolts (normal resting membrane potential is
between −50 and −60 millivolts). The channels responsible for
the action potentials allow particularly large numbers of calcium
ions to enter along with smaller numbers of sodium ions; they are
 therefore called calcium-sodium channels.

SLOW WAVES SPIKE POTENTIAL

slow undulating changes in True action potential that
RMP of GI smooth muscle ( occurs when RMP of GI smooth
5-15 mV in intensity) muscle rises above 40MV
Freq:3/min-body of stomach
12/min -duodenum
8-9/min-terminal ileum
Cause: Interstitial cells of Cajal Opening of slow Ca-Na
( electrical pacemakers) channels
changes MP cyclically
Functions:a)frequency Ca++ Ions entering GI muscle
determines rhythm of fiber cause muscle to contract
contraction (peristalsis)
b) Not true action potentials,
but control spike potentials
(FROM HANDOUTS)

● Enteric Nervous System

a. It lies in the wall of the gut
b. Two plexuses:
■ Myenteric plexus or Auerbach's plexus
● outer plexus located between the muscle layer
● stimulation causes increases: “tone” of gut wall,
intensity of contraction, rhythmical contraction,
velocity of conduction
● inhibiting pyloric sphincter, ileocecal valve
sphincter, lower esophageal sphincter
■ Submucosal plexus or Meissner’s plexus
● inner plexus that lies in the submucosa
● controlling function in the inner wall

●
●
●
●
● Stages of swallowing
Divided into:
1. Voluntary Stage- w/c initiates the swallowing process
2. Pharyngeal Stage - w/c is involuntary and constitutes
passage of food through the pharynx into the esophagus
3. Esophageal Stage- another involuntary phase that transport
food from the pharynx to the stomach
Handouts:
1. Tongue pushes food back
2. Soft palate seals nose from the throat
3. Throat muscles squeezes food down
4. Vocal cords close to prevent choking
5. Esophagus opens to let food pass down stomach

● HCl secretion in the stomach

○ Parietal ( or Oxyntic) cells which secrete HCl and Intrinsic
Factor
■ The HCl is formed at the villus-like projections inside
these canaliculi to the secretory end of the cell
■ The main driving force for HCl secretion by the
parietal cells is a hydrogen-potassium (H+-K+
adenosine triphosphatase [ATPase])
■ Hydrochloric Acid Is as Necessary as Pepsin for
Protein Digestion in the Stomach. ​The pepsinogens
have no digestive activity when they are first secreted.
However, as soon as they come into contact with
hydrochloric acid and especially when they come into
contact with previously formed pepsin plus the
hydrochloric acid they are activated to form pepsin.

●
●
●
●
●
●
●
●
 ●
● Regulation of pancreatic secretion
3 Basic Stimuli That Cause Pancreatic Secretion:
1. Acetylcholine , which is released from the parasympathetic
vagus nerve endings and from other cholinergic nerves in
the enteric nervous system
2. Cholecystokinin which is secreted by the duodenal and
upper jejunal mucosa when food enters the small intestine
3. Secretin, which is also secreted by the duodenal and jejunal
mucosa when highly acidic food enters the small intestine

● The Acetylcholine & Cholecystokinin stimulates the acinar

cells of the pancreas causing production of large quantities
of pancreatic digestive enzymes but relatively small
quantities of water and electrolytes to go with the enzymes
.
● Without water , most of the enzymes remain temporarily
stored in the acini and ducts until more fluid secretion
comes along to wash them into the duodenum
● Secretin - stimulates secretion of large quantities of water
solution of sodium bicarbonate by the pancreatic ductal
epithelium.

● Digestive enzymes secreted in the different parts of the

gastrointestinal tract

Mou Esopha Stoma Pancreas Liv SI LI

th gus ch er
Carbs Ptya Amylase Sucras
lin e
Maltas
e
Isomal
tase
Lactas
e
Prote Pepsin Trypsin Peptid
ins ogen Chymotrypsin ases
Carboxypolyp
eptidase
Fats Lipase Bil Lipase
Cholesterol e
esterase
Phospholipase

Muc Mucus Mucus Mucus Muc

us us
HCl NaHCO​3
IF
● HCl provides acidic environment for pepsinogen to become
pepsin
● NaHCO​3​ provides basic environment

● Anatomical basis of absorption of the small intestines (pg.

837)
Absorption of Water (p. 838)
Water Is Transported Through the Intestinal Membrane by
Osmosis. Water is absorbed from the gut when the chyme is
dilute, and it moves into the intestine when hyperosmotic
solutions enter the duodenum. As dissolved substances are
absorbed from the gut, the osmotic pressure of the chyme tends to
decrease, but water diffuses so readily through the intestinal
membrane that it almost instantaneously “follows” the absorbed
substances into the blood. Thus, the intestinal contents are always
isotonic with the extracellular fluid.
Absorption of Ions (p. 838)
Sodium Is Actively Transported Through the Mucosal
Epithelium.​ Sodium is actively transported from inside the
intestinal epithelial cells through the basal and side walls
(basolateral membrane) of these cells into the paracellular spaces;
this decreases the intracellular sodium concentration. This low
concentration of sodium provides a steep electrochemical
gradient for sodium movement from the chyme through the brush
border and into the epithelial cell cytoplasm. The osmotic
gradient created by the high concentration of ions in the
paracellular spaces causes water to move by osmosis through the
tight junctions between the apical borders of the epithelial cells
and, finally, into the circulating blood of the villi.

Aldosterone Greatly Enhances Sodium Absorption. Dehydration

leads to aldosterone secretion by the adrenal glands, which
greatly enhances sodium absorption by the intestinal epithelial
cells. The increased sodium absorption then causes secondary
increased absorption of chloride ions, water, and some other
substances. This effect of aldosterone is especially prominent in
the colon.
Cholera Causes Extreme Secretion of Chloride Ions, Sodium
Ions, and Water From the Crypts of Lieberkühn.​ The toxins of
cholera and some other diarrheal bacteria can stimulate the
secretion of sodium chloride and water to such a great degree that
as much as 5 to 10 liters of water and salt can be lost each day as
diarrhea. In most instances, the life of a person with cholera can
be saved through oral administration of large amounts of sodium
chloride and glucose solution to make up for the losses.
Calcium, Iron, Potassium, Magnesium, and Phosphate Ions Are
Actively Absorbed.
• Calcium ions are actively absorbed in relation to the need of the
body for calcium. Calcium absorption is controlled by parathyroid
hormone and vitamin D.The parathyroid hormone activates
vitamin D in the kidneys, and the activated vitamin D in turn
greatly enhances calcium absorption.
• Iron ions are also actively absorbed from the small intestine, as
discussed in Chapter 33.
• Potassium, magnesium, phosphate, and probably other ions can
also be actively absorbed through the mucosa.

Absorption of Carbohydrates (p. 840)

Essentially All Carbohydrates Are Absorbed in the Form of
Monosaccharides.
The most abundant of the absorbed monosaccharides is glucose,
which usually accounts for more than 80 percent of the absorbed
carbohydrate calories. Glucose is the final digestion product of our
most abundant carbohydrate food, the starches.
Glucose Is Transported by a Sodium Co-Transport Mechanism.
Active transport of sodium through the basolateral membranes
into the paracellular spaces depletes the sodium inside the cells.
The low intracellular sodium concentration provides an
electrochemical gradient to move sodium through the brush
border of the enterocyte to its interior by secondary active
co-transport. The sodium combines with a transport protein
called SGLUT-1 that requires another substance, such as glucose,
to bind simultaneously. When intestinal glucose combines with
SGLUT-1, sodium and glucose are transported into the cell at the
same time.
Other Monosaccharides Are Transported. G ​ alactose is
transported by the same mechanism as glucose. In contrast,
fructose is transported by facilitated diffusion all the way through
the enterocyte but is not coupled with sodium transport. Much of
the fructose is converted to glucose within the enterocyte and
finally is transported to blood in the form of glucose.

Absorption of Proteins (p. 841)

Most Proteins Are Absorbed Through the Luminal Membranes
of the Intestinal Epithelial Cells in the Form of Dipeptides,
Tripeptides, and Free Amino Acids. The energy for most of this
transport is supplied by sodium cotransport mechanisms in the
same way that sodium co-transport of glucose and galactose
occurs. A few amino acids do not require this sodium co-transport
mechanism but, instead, are transported by special membrane
transport proteins in the same way that fructose is
transported—via facilitated diffusion. More than 10 different
transport proteins are required for absorption of amino acids.

Absorption of Fats (p. 841)

Monoglycerides and Fatty Acids Diffuse Passively Through the
Enterocyte Cell Membrane to the Interior of the Enterocyte​.
Lipids are soluble in the enterocyte membrane. After entering the
enterocyte, the fatty acids and monoglycerides are mainly
recombined to form new triglycerides. A few of the
monoglycerides are further digested into glycerol and fatty acids
 by an intracellular lipase. Triglycerides themselves cannot pass
through the enterocyte membrane.
Chylomicrons Are Secreted From the Enterocytes by Exocytosis​.
The reconstituted triglycerides aggregate within the Golgi
apparatus into globules that contain cholesterol and
phospholipids. The phospholipids arrange themselves with the
fatty portions toward the center and the polar portions on the
surface, providing an electrically charged surface that makes the
globules miscible with water. The globules are released from the
Golgi apparatus and are secreted by exocytosis into the
basolateral spaces. From there, they pass into the lymph in the
central lacteal of the villi. These globules are then called
chylomicrons.

Chylomicrons Are Transported in Lymph.​ From the basolateral

surfaces of enterocytes, the chylomicrons wind their way into the
central lacteals of the villi and are then propelled, along with the
lymph, upward through the thoracic duct to be emptied into the
great veins of the neck.

● Pathophysiology of achalasia and megacolon

Achalasia Is a Condition in Which the Lower Esophageal
Sphincter Fails to Relax.
● When the lower esophageal sphincter fails to relax,
swallowed material can build up, stretching the esophagus.
Over months and years the esophagus can become
markedly enlarged, a condition called megaesophagus.

Severe Constipation Can Lead to Megacolon.

● When large quantities of fecal matter accumulate in the
colon for an extended time, the colon can distend to a
diameter of 3 to 4 inches. This condition is called
megacolon.Hirschsprung’s disease, the most frequent cause
of megacolon, results from a lack or deficiency of ganglion
cells in the myenteric plexus, usually in a segment of the
sigmoid colon of newborn males.

●
●
 ●
●
●
● Peptic ulcer causes (pg 844 guyton)
1. High acid and pepsin content
2. Irritation
3. Poor blood supply
4. Poor secretion of mucus
5. Infection (H.pylori)

V. THE BODY FLUIDS AND KIDNEYS (8)

● Acid- Base Regulation and Disorders
Major Buffer System
Buffer: ​System that can resist change in pH; composed of a weak acid or
a weak base and its corresponding salt

Acid- ​is a substance capable of dissociating to yield H+ ion and become

more negatively charged (electron acceptor);when hydrogen ions
accumulate in a solution, it becomes more acidic (H+) increases = more
acidity.

Base-​is a substance that can accept H+ ion

-is a chemical that will remove hydrogen ions from the solution and it
has a negative charge (or extra electrons) to donate to hydrogen ions
and thus create a bond with hydrogen.

● Acids are being created constantly through metabolism and

must be buffered, transported away from cells and
eliminated from the body
● Phosphate-important renal tubular buffer
● Ammonia-important renal tubular buffer
● Proteins-important intracellular and plasma buffers
● Bicarbonate - is the most important ECF buffer

Cause Organ Affected

Respiratory Acidosis ↑ H2CO3 Lungs
Respiratory Alkalosis ↓H2CO3 Lungs
Metabolic Alkalosis ↑ HCO3 Kidneys
Metabolic Acidosis ↓HCO3 Kidneys

pH pCO2 HCO3
( 7.35-7.45) (21-28mmol/
(35-45mmHg) L)
Respiratory <7.35 Increased Normal
Acidosis
Respiratory >7.45 Decreased Normal
Alkalosis
Metabolic >7.45 Normal Increased
Alkalosis
Metabolic <7.35 Norma; Decreased
Acidosis

Primary Secondary
Compensation Compensation
Respiratory Acidosis RENAL:↑ RESPIRATORY, if
Reabsorption of HCO3 defect is not in the
(↓Urination) respiratory center:
↓retention of CO2
(
HYPERVENTILATION
)
Respiratory Alkalosis RENAL:↓ RESPIRATORY, if
Reabsorption of HCO3 defect is not in the
(↑Urination) respiratory center:
↑retention of CO2
 (
HYPOVENTILATION)
Metabolic Alkalosis RESPIRATORY: ↑ RENAL,if kidney
retention of CO2 ( functional is
HYPOVENTILATION) normal:↓reabsorptio
n of HCO3
(↑URINATION)
Metabolic Acidosis RESPIRATORY:↓rete RENAL, if kidney
ntion of CO2 function normal: ↑
(HYPERVENTILATIO reabsorption of HCO3
N) (↓ URINATION)

● Renal Blood Flow

● Renal Regulation of Potassium

○ The following stimulates potassium uptake into cells
■ Insulin
Diabetes mellitus – hyperkalemia
■ Aldosterone
↑K+ intake = ↑aldosterone secretion
Conn’s syndrome = excess aldosterone secretion = K+
into cells = hypokalemia
Addison’s disease = deficient aldosterone secretion =
K+ in ECF + K+ renal retention = hyperkalemia
■ β-adrenergic stimulation
 ↑ catecholamines (epinephrine) = activation of
β2-adrenergic receptor = K+ from ECF to ICF
β-adrenergic receptor blockers (propranolol) = K+
from ICF to ECF = hyperkalemia

○ Acid-Base abnormalities can cause changes in potassium

distribution
■ Metabolic acidosis: ↑ K+ concentration in ECF
from ICF
■ Metabolic alkalosis: ↓ K+ concentration in ECF
■ ↑ H+ ions = ↓ Na+-K+ ATPase activity = ↓ K+
cellular uptake = ↑ K+ ECF conc.
○ Cell Lysis ↑ K+ ECF concentration
○ Strenuous Exercise + β-adrenergic receptor
blockers/insulin deficiency = K+ from Skeletal muscle =
Hyperkalemia
○ ↑ ECF osmolarity = H2O out of the cells = cellular
dehydration = ↑ K+ ICF concentration causing K+ to diffuse
from ICF to ECF

● Diuretics and Kidney Diseases

Type Sites of action Therapeutic Example
use

Carbonic Proximal · Cystinuria Acetazolamide

anhydrase Tubule · Glaucoma
inhibitors · Acute
mountain
· H​ CO​3 sickness
depletion · Metabolic
can cause alkalosis
hyperchlore
mic
metabolic
acidosis
Loop diuretics Ascending · Ethacrynic acid
loop of Henle Hypertensio
Blocks n (impaired Furosemide
Na-K-Cl renal
cotransporter function) Bumetanide
· Congestive
· Enhances heart failure
Ca and Mg (moderate to
excretion severe)
· Greater · Acute
diuresis pulmonary
edema
· Chronic or
acute renal
failure
· Nephrotic
syndrome
·
Hyperkalemi
a
· Chemical
intoxication
(to ↑urine
flow)

Thiazide Distal · Hydrochlorothia

diuretics Convoluted Hypertensio zide
Tubule n
Blocks · Congestive Chlorthalidone
Na-Cl heart failure
cotransporter (mild)
· Renal calculi
 · Less · Nephrogenic
reabsorption diabetes
of H​2​O and insipidus
electrolytes · Chronic
· Increase Cl renal failure
excretion (as an
over HCO​3 adjunct to
excretion loop diuretic)
· Decreased ·
Ca excretion Osteoporosi
s

Potassium-spar Collecting · Chronic liver Spironalactone

ing diuretics Tubule failure / Eplerenone
· Congestive (aldosterone
Blocks Na/K heart failure antagonists)
exchange (due to
Often used with hypokalemia Amiloride /
thiazide to ) Triamterene
restrict K loss (Na-channel
blockers)
· Principal
cells:
transport
Na, K, H​2​O
· Intercalated
cells:
secretion of
H and HCO​3
Osmotic agents Proximal · Reduce Mannitol
Tubule pre-surgical
· Blocks H​2​O Descending or
reabsorption loop of Henle post-trauma
· Large water Collecting intracranial
loss Duct pressure
· Small · Prompt
electrolyte removal of
loss toxins
· Does not
remove
large
amounts of
Na​+
· Can cause
hypernatrem
ia

● Acute renal failure

○ Prerenal
■ abnormality originating outside the kidneys
■ e.g. heart failure = reduced CO + low BP = decreased
blood supply to kidneys (oliguria)
■ total cessation of urine output: anuria
○ Intrarenal
■ abnormalities within kidney itself
■ injures glomerular capillaries/small renal vessels
(acute glomerulonephritis—abnormal immune
reaction)
■ damages renal tubular epithelium
(tubular necrosis—destruction of epithelial cells in
tubules from severe ischemia, poisons, toxins,
medications)
■ damages renal interstitium
○ Postrenal
 ■ urinary collecting system: calyces to outflow from
bladder
■ most common: nephrolithiasis caused by
precipitation of calcium, urate or cystine
● Chronic renal failure
○ progressive and irreversible loss of large numbers of
functioning nephrons
○ serious clinical symptoms do not occur until functional
nephron count falls to at least 70%-75% below normal
● End-stage renal disease
○ Progressive deterioration of kidney function and further
loss of nephrons ‘til dialysis
○ Leading causes of ESRD: diabetes mellitus and hypertension
| Obesity

●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
● Reabsorption and Secretion Among the Different Parts of the
Nephrons

● Urine Concentration and Dilution

○

●
●
●
●
●
●
●
●
● Glomerular feedback mechanism
○ 2 variables that influence sodium and water excretion
■ Glomerular filtration: 180 L/day
■ Tubular reabsorption: 178.5 L/day
○ Excretion = Glomerular filtration - Tubular reabsorption
○ Normal urine excretion: 1.5 L/day
○ 2 intrarenal compensations
■ Glomerulotubular balance: increased tubular
reabsorption of filtered NaCl
■ Macula densa feedback: increased NaCl delivery to DT
causes afferent arteriolar constriction, thus returning
GFR to normal
○ Feedback mechanisms
■ Key components of renal-body fluid feedback
regulating body fluid volumes and arterial pressure:
Pressure natriuresis​ = Natriuresis + Diuresis
● Pressure natriuresis: rise in NaCl excretion that
occurs with elevated blood pressure
● Pressure diuresis: effect of increased blood
pressure to raise urinary volume excretion
■ Sympathetic Nervous System: ​Arterial Baroreceptor
and Low-Pressure Stretch Receptor Reflexes
(carotid sinus and aortic arch)
● constriction of renal arterioles = decreased GFR
● increased tubular reabsorption of salt and
water
● stimulation of renin release and increased
angiotensin II and aldosterone formation =
increases tubular reabsorption
■ Renin-angiotensin system​: powerful amplifier to
pressure natriuresis
● Angiotensin II: one of the most powerful
controllers of sodium excretion
 ● above normal sodium intake = ↓ renin
secretion = ↓ angiotensin II formation =
↓tubular reabsorption of sodium = ↑excretion
of sodium and water
● below normal sodium intake = ↑angiotensin II
= ↑aldosterone = sodium and water retention =
oppose reductions in arterial blood pressure
■ Aldosterone
● increases sodium [and water] reabsorption
(cortical collecting tubules) and increase
potassium excretion in urine
● aids pressure natriuresis mechanism
■ ADH​: important in regulating ECF volume
● ↑ADH levels = severe reductions in ECF
sodium ion concentration = slight ↑ BP
■ Atrial Natriuretic Peptide​: most important of the
natriuretic hormones

● Atrionatriuretic peptide
○ released by cardiac atrial muscle fibers; excessive or lack of
ANP does not cause major changes in blood volume
○ stimulus: increased stretch of the atria (from excess blood
volume)
○ acts on kidneys to cause small increases in GFR and
decreases in sodium reabsorption in ​collecting ducts​ =
increased excretion of salt and water (helps compensate for
excess blood volume)
○ changes in ANP levels probably help minimize changes in
blood volume during various disturbances (e.g. increased
salt and water intake)
VI. ENDOCRINOLOGY AND REPRODUCTION (11)
● Spermatogenesis
Spermatogenesis is the Process of Formation of Spermatocytes
From Spermatogonia. Spermatogenesis is ​initiated at puberty​,
continues throughout the remainder of a man’s life, and ​takes
place in the walls of the seminiferous tubules​. The walls of the
tubules are composed of two compartments separated by tight
junctions between the Sertoli cells:

• ​The basal layer​, which consists of the Leydig cells and the
spermatogonia
• ​The adluminal layer​, which is made up of Sertoli cells and
spermatocytes
The initial step in the process is transformation of type A
spermatogonia, which are epithelioid-like cells, to type B
spermatogonia, a process involving four divisions.The type B cells
embed in the Sertoli cells. Inassociation with the Sertoli cells, the
type B cells are transformed to primary spermatocytes and then,
in a step involving the first meiotic division, to secondary
spermatocytes. The secondary spermatocytes undergo a second
meiotic division, yielding spermatids, each of which has 23
unpaired chromosomes. The steps described are stimulated by
testosterone and follicle stimulating
hormone (FSH).
Spermiogenesis Is the Process of Transformation of the
Spermatids, Which Are Still Epithelioid, to Sperm Cells.
The process of spermiogenesis takes place with the cells
embedded in the Sertoli cells; it requires estrogen and FSH. Once
the sperm cells are formed, they are extruded into the lumen of
the tubule in a process stimulated by luteinizing hormone (LH).
The first division of the type A spermatogonia to extrusion of the
sperm cells requires a period of approximately 64 days.The newly
formed sperm cells are not functional and require a maturation
process, which takes place in the epididymis over a period of 12
days. Maturation requires both testosterone and estrogen. The
mature sperm are stored in the vas deferens
● Amenorrhea in Anorexia Nervosa ​(cant find sa guyton ; this is
from ncbi)
Amenorrhea is one of the cardinal features of anorexia nervosa
and is associated with hypothalamic dysfunction. Earlier
theories of weight loss, decreased body fat, or exercise do not
fully explain the etiology of amenorrhea in anorexia nervosa.
Disturbances in central dopaminergic and opioid activity have
been described in anorexia nervosa and both these substances
are known to modulate gonadotropin-releasing hormone
(GnRH)-mediated luteinizing hormone (LH) release. Serum LH,
follicle-stimulating hormone (FSH), estradiol, and prolactin
levels were measured at baseline and after administration of
metoclopramide (a central D-2 dopamine receptor blocker) in
10 newly diagnosed women with anorexia nervosa and in 10
healthy age-matched controls. Basal prolactin levels and the
prolactin response to metoclopramide were significantly
impaired in the group with anorexia nervosa. Metoclopramide
did not induce a significant rise in LH levels in either the
anorexic or the control groups. Neurotransmitter abnormalities
may influence hypothalamic dysfunction in anorexia nervosa
but the exact mechanism remains to be determined.

● Ovulation
Ovulation (p. 1041)
Ovulation in a woman who has a normal 28-day female sexual
cycle occurs 14 days after the onset of menstruation .About 2 days
before ovulation, a surge of LH secretion,6- to 10-fold above
normal, occurs. This LH surge is necessary for ovulation to occur.
In an action associated with the LH surge, the thecal cells begin to
secrete progesterone for the first time. The blood flow in the
thecal layers increases at this time, as does the rate of
transudation of fluid into the vesicle. The thecal cells also secrete
a proteolytic enzyme into the follicular fluid. At a point of
weakness in the wall of the follicle on the surface of the ovary, a
protrusion, or stigma, develops.The wall ruptures at the stigma
within 30 minutes of its formation, and within minutes of the
rupture, the follicle evaginates and the oocyte and surrounding
layers of granulosa cells—referred to as the corona radiata—leave
 the vesicle and enter the abdominal cavity at the opening to the
fallopian tube.

● Implantation
(from constanzo)
Implantation. The blastocyst floats freely in the uterine cavity for
1 day and then implants in the endometrium 5 days after
ovulation. The receptivity of the endometrium to the fertilized
ovum is critically dependent on a low estrogen/progesterone
ratio and corresponds to the period of highest progesterone
output by the corpus luteum. At the time of implantation, the
blastocyst consists of an inner mass of cells, which will become
the fetus, and an outer rim of cells called the trophoblast. The
trophoblast invades the endometrium and forms an attachment to
the maternal membranes. Thus the trophoblast contributes the
fetal portion of the placenta. At the point of implantation, under
stimulation by progesterone, the endometrium differentiates into
a specialized layer of decidual cells. Eventually, the decidua will
envelop the entire conceptus. Trophoblastic cells proliferate and
form the syncytiotrophoblast, whose function is to allow the
blastocyst to penetrate deep into the endometrium.

● 5-alpha Reductase Inhibitor

BRS:
*   Accessory sex organs (e.g., prostate) contain 5a-reductase,
which converts testosterone to
its active form, dihydrotestosterone.
*  5a-reductase inhibitors (finasteride) may be used to treat
benign prostatic hyperplasia
because they block the activation of testosterone to
dihydrotestosterone in the prostate

●
●
●
●
●
●
●
● Male Sexual Act
The male sexual act is the process that culminates in ejaculation of
several hundred million viable sperm.The sperm cells are
contained in a mixture of fluids produced by the male
reproductive organs that is called semen and includes the
following:
• ​Seminal vesicle fluid​, which makes up ​60 percent of the total
volume of the semen. It contains mucoid, prostaglandin E2,
fructose, and fibrinogen.
• Prostatic fluid, which makes up 20 percent of the semen
volume and contains NaHCO3 (pH 7.5), clotting enzyme, calcium,
and profibrinolysin.
• ​Sperm cells- ​The average volume of semen ejaculated at each
coitus is 3.5 milliliters, and each milliliter of semen contains
approximately 120 million sperm cells. For normal
fertility, the sperm count per milliliter must be greater than 20
million.

The sexual act takes place in three stages:

1. Erection and lubrication​. Erection is the process of filling
the erectile tissue of the penis with blood at a pressure level
near that of the arterial pressure.The arteries leading to the
erectile tissue dilate in response to parasympathetic
impulses, which stimulate release of nitric oxide at the
nerve endings on the arterial smooth muscle.
Parasympathetic reflexes also stimulate secretion of mucus
by the urethral glands and bulbourethral glands. The mucus
aids in vaginal lubrication during coitus.
2. Emission. Emission is the process of stimulating the
smooth muscle surrounding the seminal vesicles, vas
deferens, and prostate gland, causing the organs to empty
their contents into the internal urethra, a process elicited by
sympathetic reflexes from L1 and L2.
3. Ejaculation​. Ejaculation is a reflex elicited in response to
distention of the internal urethra. The reflex results in
contraction of the ischiocavernosus and bulbocavernosus
muscles and the muscles of the pelvis, causing compression
in the internal urethra and propulsion of the semen out of
the urethra.
 ● Hypothyroidism
○   Hypothyroidism causes listlessness, slowed speech,
somnolence, impaired memory,and decreased mental
capacity.
○ often initiated by autoimmunity against the thyroid gland
(Hashimoto’s disease)
○ Autoimmunity destroys the gland rather than stimulates it.
○ Thyroid glands of most of these patients first demonstrate
autoimmune “Thyroiditis”
○ Progressive deterioration and finally fibrosis of the gland,
with resultant diminished or absent secretion of thyroid
hormone.

● Management of Hyperthyroidism
● Type 2 Diabetes Mellitus
● Parathyroid Hormone and Associated Disorders
● Vitamin D3

VII.
NEUROMUSCULOSKELETAL SYSTEM(14)
● Neuromuscular junction events
1. Presynaptic terminal: ​choline acetyltransferase converts
CoA & choline to ACh. Synaptic vesicles stores ACh, ATP,
Proteoglycan
2. Presynaptic terminal depolarize: opens calcium channels
which inc calcium permeability
3. Calcium uptake​→ synaptic vesicle fuse with plasma
membrane ​→ ​ACh release into synaptic cleft
4. ACh diffuse to postsynaptic membrane & bind to nicotinic
receptors
5. Depolarization of specialized muscle end plate (end plate
potential in postsynaptic membrane)
6. Depolarization of adjacent muscle membrane ​→ action
potential à contraction
7. Degradation of ACh by acetylcholine transferase to
Acetyl-CoA & choline

● Steps in excitation-contraction coupling in skeletal muscle

1 Action Potentials in the muscle cell membrane initiate
depolarization of the T tubules
2 Depolarization of T tubules
3 Intracellular calcium increases
4 Calcium binds to troponin C ​→​ **Cross bridge cycle
5 Relaxation ​→​ intracellular calcium concentration decrease
6 mechanism of tetanus: no ATP

**Cross Bridge Cycle

1 No ATP is bound to myosin
2 ATP then binds to myosin
3 Myosin displaced toward the plus end of actin
 4 Myosin attaches to new site on actin ​→ power
force-generating stroke
5 The cycle repeats as long as calcium is bound to troponin
C

● Temporal vs. spatial summation

TEMPORAL SUMMATION SPATIAL SUMMATION

Summing ​successive Summing ​simultaneous

discharges from a single postsynaptic potentials by
presynaptic terminal, if occur activating multiple terminals
rapidly, adding to one another on widely space areas of
neuronal membrane

● Tonic sensory receptors vs. rate sensory receptors

TONIC SENSORY RECEPTORS RATE SENSORY RECEPTORS

Slowly adapting receptors Rapid adapting receptors

Detect continuous stimuli React to change in stimuli

strength strength

Constantly apprise the brain of Predictive function

the status of the body in
relation to its surrounding

Pain receptors Pacinian corpuscle, joint

receptor

●
●
●
●
● Classification of nerve fibers

● Types of mechanoreceptors and sensation encoded

●
●
●
●
●
●
●
●
 ● Fast pain vs. slow pain
FAST PAIN SLOW PAIN

Felt w/in 0.1 sec after Felt after 1 sec or more;

stimulus increases slowly over
many sec/mins

AKA sharp pain, AKA slow burning pain,

pricking pain, acute aching pain, throbbing
pain, electric pain pain, nauseous pain,
chronic pain

Not felt in most deep Associated with tissue

tissue destruction can lead to
prolonged, unbearable
suffering

Stimuli Mechanical or thermal Mostly Chemical;

sometimes mechanical
or thermal

Pain fiber Aδ fibers Type C fibers

velocity 6-30 m/sec 0.5-2 m/sec

Path in spinal Neospinothalamic Paleospinothalamic

cord to brain Tract tract

localization Can be Localized more Imprecise

exactly

Neurotransmitt Glutamate Substance P

er

●
●
 ● Fever
-set-point temperature: ​37.1 °C
Pyrogen, increase IL-1 production ​→ IL-1 increase production of
prostaglandins ​→ prostaglandins increase set-point temp ​→
activation of heat-generating mechanisms

● CSF formation and flow

- 150 ml present in ventricles
- 500 ml/day
- secreted from choroid plexuses

Lateral ventricles ​→ third ventricles ​→ aqueduct of Sylvius ​→

fourth ventricle ​→ two lateral foramina of Luschka a midline
foramen of Magendie ​→ cisterna magna ​→ subarachnoid space ​→
arachnoid villi ​→​ venous sinuses

● Errors of refraction and their correction

Emmetropia = normal vision
Hyperopia (can’t see near Myopia (can’t see far object)
object)

Farsightedness Nearsightedness

Eyeball too short Eyeball too long

Light rays focus behind the Light rays to focus front of the
retina retina

Convex lens Concave lens

Astigmatism = imperfect image ; cylindrical lens
Keratoconus = odd shaped, bulging cornea ; contact lens
Cataract = opaque lens ; surgical removal of lens
 Presbyopia = loss of accommodation by lens

● Photochemistry of vision
11-cis retinal ​→ all-trans retinal ​→ metarhodopsin II ​→
activation of G protein (transducin) ​→ activation of
phosphodiesterase ​→ decrease cCGMP ​→ closure of Na​+ ​channels
→​ hyperpolarization ​→​ decreased glutamate release

● Effect of lesions in the optic pathway on the fields of vision

Cutting the optic nerve = blindness in the ipsilateral eye
Cutting the optic chiasm = heteronymous bitemporal hemianopia
Cutting the optic tract = homonymous contralateral hemianopia
Cutting the geniculocalcarine tract = homonymous hemianopia
with macular sparing

● Pattern of vibration of the basilar membrane for different

sound frequencies
BASE of the Basilar APEX of the Basilar
Membrane Membrane

Near the oval & round Near the helicotrema

window

Narrow & stiff Wide & compliant

High frequencies Low frequencies

●
●
●
●
● Sympathetic vs. parasympathetic system (physiologic
anatomy, neurotransmitters, receptor types, actions)

●
●
●
●
●
●
●
●
●
●
●
●
●
●
 ● Pharmacology of ANS
Drugs that act on Drugs that act on Drugs that
ADRENERGIC effector CHOLINERGIC stimulate or block
organ effector organ sympathetic &
parasympathetic

Sympathomimetic Parasympathomimi Stimulate

drugs c Drugs autonomic
● Epinephrine ● Pilocarpine postganglionic
● norepinephrine ● methacholine neurons
● methoxamine ● nicotine
● phenylephrine (A) Parasympathetic
● isoproterenol (B) Potentiating Ganglionic
● albuterol (B2) effect-anticholinest blocking Drugs
erase Drugs ● tetraethyl
Drugs that cause ● Neostigmine ammonium
release of ● pyridostigmin ion
norepinephrine from e ● hexamethoni
nerve ending ● ambenonium um ion
● ephedrine ● pentolinium
● tyramine Block Cholinergic
● amphetamine Activity at Effector
Organ-Antimuscari
nic drug
● atropine
● homatropine
● scopolamine

Drugs that block Adrenergic Activity

Reserpine Prevent synthesis & storage of NP in

synthetic nerve ending
 Guanethidine Block release of NP from sympathetic
nerve ending

Phenoxybenzamine, Blocks alpha 1 & 2 adrenergic receptor

Phentolamine

Prazosin, Terazosin Block alpha 1 adrenergic receptor

Yohimbine Alpha 2 adrenergic receptor blocker

Propanolol Block beta 1 & 2 receptor

Metoprolol, atenolol, Block beta 1 receptor

Nebivolol

V. AVIATION, DIVING, SPORTS PHYSIOLOGY (3)

● Acclimatization to Low PO​2
1. A great increase in pulmonary ventilation
2. Increased numbers of red blood cells
3. Increased diffusing capacity of the lungs
4. Increased vascularity of peripheral tissues
5. Increased ability of the tissue cells to use oxygen despite low
PO2

● Decompression sickness
-large amounts of nitrogen have dissolved in the body and
suddenly the person comes back to the surface of the sea
-significant quantities of nitrogen bubbles can developed
intracellular or extracellular causes damage depending on the
amount and size of bubbles
- “bends” = joints and muscle ; “the chokes” = capillaries of the
lungs
-tank decompression
 ● Fast-twitch vs. slow twitch muscle fibers
FAST-TWITCH MUSCLE FIBER SLOW-TWITCH MUSCLE
FIBER

Larger in Diameter Organize for endurance

More mitochondria &
myoglobin

Phosphagen Glycogen-Lactic Aerobic System

Acid System

More Capillaries in Vicinity

Gastrocnemius Soleus

Sprint Marathon
VIII. BLOOD CELLS, IMMUNITY, AND BLOOD COAGULATION
● RBC Disorders
= Quantitative RBC disorders may be classified into =

1. ANEMIA​-Term used to denote conditions associated with

decreased to below normal Hgb concentration, erythrocyte
count, or hematocrit (Hct).
-Best defined in reference to a decreased hgb level
-Decreased amount of hgb/RBC = Decreased O2 reaching
the tissues/ organs of the body
​ -Can be classified according to:
a.Morphology-uses RBC indices ( MCV, MCH,MCHC)
b.Etiology/ Cause
​2. Erythrocytosis and Polycythemia
-Increased RBCs in the circulation

= Conditions associated with anemia and erythrocytosis can

be subdivided into =

1. Absolute​ - true increased / decreased in red cell mass

2. Relative-​ secondary to change in plasma volume

General Classification of Anemia

1. Absolute Anemia -RBC mass decreased, plasma volume
normal
Mechanism:
a. Decreased delivery of RBC into circulation
-Caused by impaired or defective production
-Bone marrow fails to respond; reticulocytopenia
 b. Increased loss of RBCs from circulation
- Caused by acute bleeding or accelerated
destruction(haemolytic)
- Bone marrow can respond; reticulocytosis

2. Relative (Pseudo) Anemia-RBC mass normal, plasma volume

increased
-Reticulocyte normal;Causes include conditions that result in
hemodilution
(pregnancy, hyperproteinemia, IV fluids)

ANEMIA – deficiency of hemoglobin in the blood

1. Blood Loss occurs after significant hemorrhage. The body is

Anemia able to replace the plasma within 1 to 3 days;
however, the concentration of red blood cells
remains low. After significant hemorrhage, a
 period of 3 to 4 weeks is required to return the
number of red blood cells to normal levels.

2. Aplastic is the result of nonfunctioning bone marrow,

Anemia which may be due to exposure to gamma
radiation for cancer treatment or toxic
chemicals such as insecticides or benzene in
gasoline. Autoimmune disorders such as lupus
erythematosus result in an immune system
attack on the healthy cells of the bone marrow,
which destroys stem cells and may lead to
aplastic anemia. Individuals with severe aplastic
anemia usually die unless they are treated with
blood transfusions or bone marrow transplants.

3. Megaloblastic is the result of a lack of vitamin B12, folic acid,

Anemia or intrinsic factor. Lack of these substances
leads to slow reproduction of the erythrocytes
in the bone marrow. As a result, these
erythrocytes grow into large, odd-shaped cells
called ​megaloblasts.

4. Hemolytic is the result of fragile red blood cells that

Anemia rupture as they pass through the capillaries.
With hemolytic anemia, the number of red blood
cells that form is normal or in excess of normal;
however, because these cells are extremely
fragile, their life span is very short.

Sickle cell anemia ​is a type of hemolytic anemia

caused by an abnormal composition of the
globin chains of hemoglobin. When this
abnormal hemoglobin is exposed to low
concentrations of oxygen, it precipitates into
 long crystals inside the red blood cell. This
causes the cell to have an abnormal sickle shape
and to be extremely fragile.

POLYCYTHEMIA

Polycythemia is a condition in which the number of red blood cells in

the circulation increases owing to hypoxia or genetic aberration.
Individuals who live at high altitudes have ​physiologic polycythemia a​ s
a result of the thin atmosphere. Polycythemia can also occur in
individuals with cardiac failure because of decreased delivery of
oxygen to the tissues.

Polycythemia vera i​ s a genetic aberration in the hemocytoblastic cell

line. The blast cells continue to produce red blood cells even though
too many blood cells are presen in the circulation. The hematocrit can
rise to 60% to 70%.

Polycythemia greatly increases the viscosity of the blood; as a result,

blood flow through the vessels is often sluggish.

●
●
●
●
●
●
●
●
●
●
●
● Role of WBC in Inflammation ( Handouts)
Inflammation is characterized by:
1. Vasodilation ​of the local blood vessels with consequent
excess local blood flow
2. Increased permeability of the capillaries, ​allowing
leakage of large quantities of fluid into the interstitial
spaces;
3. often clotting of the fluid in the interstitial spaces
because of increased amounts of fibrinogen and other
proteins leaking from the capillaries
4. Migration of large numbers of granulocytes and
monocytes ​into the tissue; and
5. Swelling ​of the tissue cells

Lines of Defense Response to Inflammation

1st Line of defense in Tissue- Tissue macrophages & Physical
Barriers
2nd Line of defense- ​Neutrophil Invasionof the Inflamed Area
3rd Line of defense-​Monocytes-macrophages invasion of
inflamed area
4th Line of defense-​Increased production of granulocytes and
Monocytes by Bone Marrow
When tissue injury occurs, multiple substances are released that cause
secondary changes in the tissue. These substances increase local blood
flow and the permeability of the capillaries, which cause large quantities
of fluid to leak into the interstitial spaces, the migration of large
numbers of granulocytes and monocytes into the tissues, and local
swelling. One of the first results of inflammation is to “wall off” the area
of injury from the remaining tissues. The tissue spaces and lymphatics
in the inflamed area are blocked by fibrinogen clots, so fluid barely
flows through these spaces. This walling-off procedure delays the
spread of bacteria or toxic products. The intensity of the inflammatory
process is usually proportional to the degree of tissue injury.
Staphylococci that invade the tissue liberate extremely lethal cellular
toxins, which is followed by the rapid development of inflammation.
Staphylococcal infections are characteristically walled off rapidly. By
comparison, streptococci do not cause such intense local tissue
destruction, so the walling off develops slowly. As a result, streptococci
have a far greater tendency to spread through the body and cause death
than do staphylococci, even though staphylococci are far more
destructive to the tissues.

LINE OF DEFENSE

1​ST Tissue Within minutes after inflammation begins, the

Macrophage macrophages present in the tissues
immediately begin their phagocytic actions.
Many sessile macrophages break loose from
their attachments and become mobile in
response to ​chemotactic factors. ​These
macrophages migrate to the area of
inflammation and contribute their activity.
2​ND Neutrophil During the first hour or so after inflammation
invasion begins, large numbers of neutrophils invade
the inflamed area as a result of products in the
inflamed tissue that attract these cells and
cause chemotaxis toward that area. Within a
few hours after the onset of severe acute
inflammation, the number of neutrophils
increases by as many as four- to fivefold. This
neutrophilia i​ s caused by inflammatory
products that are transported in the blood to
the bone marrow, where neutrophils from the
marrow capillaries are mobilized and move
into the circulating blood. This process results
in more neutrophils being made available to
the inflamed tissue area.

3​RD Second Along with the invasion of neutrophils,

macrophage monocytes from the blood enter the inflamed
invasion tissue and enlarge to become macrophages.
The number of monocytes in the circulating
blood is low, and the storage pool of
monocytes in the bone marrow is much less
than that of the neutrophils. The build-up of
macrophages in inflamed tissue is much
slower than that of neutrophils. After several
days to several weeks, the macrophages
become the dominant phagocytic cell in the
inflamed area because of the increased bone
marrow production of monocytes.

4​TH Increase This process results from stimulation of the

production of granulocytic and monocytic progenitor cellw;
granulocyte it takes 3 to 4 days for the newly s of the
 and marroformed granulocytes and monocytes to
monocyte reach the stage of leaving the marrow area.

● Hypersensitivity reactions
An important but undesirable side effect of immunity is the
development of allergy or other types of immune hypersensitivity.
Allergy can be caused by activated T cells and can cause skin
eruptions, edema, or asthmatic attacks in response to certain
chemicals or drugs. In some individuals, a resin in the poison ivy
plant induces the formation of activated helper and cytotoxic T
cells that diffuse into the skin and elicit a cell mediated
characteristic type of immune reaction to this plant. Some
allergies are caused by IgE antibodies. These antibodies are called
reagins, or sensitizing antibodies, to distinguish them from the
more common IgG antibodies. A special characteristic of IgE
antibodies is their ability to bind strongly with mast cells and
basophils, causing the release of multiple substances that induce
vasodilation, increased capillary permeability, and attraction of
neutrophils and eosinophils. Hives, hay fever, and asthma can
result from this mechanism.

Hypersensitivity ​- excessive or aberrant immune response;

negative effect of the immune response;an exaggerated response
to a harmless antigen that results in injury to the tissue , disease
or even death.

Cell and Coombs Classification of Hypersensitivity

(remember the pneumonic “ACID”)
1.Type 1: Anaphylactic hypersensitivity
-aka Immediate hypersensity ( occurs seconds to minutes after
contact)
 -involves basophils/ mast cells sensitized by IgE
-occurs in allergic reactions and helminth infections mechanism
2. Type 2 : Cytotoxic hypersensitivity
- Mechanism: IgM or IgG binds to cell bound antigen
-Destroy cells by phagocytosis or ADCC
- Can destroy RBC, WBC and platelets
-Example:
a.Hemolytic transfusion reaction (HTR)
-ABO blood group is of primary importance
b. Hemolytic disease of the newborn (HDN)
-ABO HDN more common
-Rh HDN: D antigen most common cause of severe HDN
c. Autoimmmune Hemolytic Anemia (AIHA)
d. Organ-specific autoimmune disease

​ 3.​ Type 3: Immune Complex hypersensitivity

-Ag and Ab complexes can be deposited in tissue causing
inflammation and complement activation.
-Examples:
a. Arthus reaction
b.Serum Sickness
c.Autoimmune disease
​4. Type 4: Delayed hypersensitivity
- Cell Mediated hypersensitivity
- Delayed type: occurs 1-3 days after exposure to an Ag
- T- cells react with antigen at injection site
 ● Anticoagulants
a Endothelial cells
b. Glycocalyx layer
c. Thrombomodulin protein
d. Fibrin fibers – adsorbed ~ 90% of thrombin to remove it from
the circulating blood
e. Anti-thrombin III or anti-thrombin – heparin : combines with
thrombin and removes it from blood
f. Heparin combines with anti-thrombin III
g. Liver, lungs, mast cells, and basophils
Anticoagulants for Clinical Use Prevention of blood coagulation
● Heparin – commercial, outside the blood
extracted from animals ● Decrease calcium
● Coumarins – warfarin, concentration
competitive binding with ● Oxalate – precipitates ; toxic
vitamin K to the body
● Decrease factors II, VII, IX, X
 ● Citrate – deionizer ;
metabolized to glucose or
ATP
● EDTA – chelating agent

Activation of Plasminogen to Form Plasmin, Then Lysis of Clots.

When a clot is formed, a large amount of plasminogen is trapped in
the clot along with other plasma proteins. This will not become
plasmin or cause lysis of the clot until it is activated. The injured
tissues and vascular endothelium very slowly release a powerful
activator called ​tissue plasminogen activator (​ t-PA); a few days later,
after the clot has stopped the bleeding, t-PA eventually converts
plasminogen to plasmin, which in turn removes the remaining
unnecessary blood clot. In fact, many small blood vessels in which
blood flow has been blocked by clots are reopened by this
mechanism. Thus, an especially important function of the plasmin
system is to remove minute clots from millions of tiny peripheral
vessels that eventually would become occluded were there no way to
clear them.

○ inhibits blood from clotting

■ Heparin
● immediately prevents/slows further
development of a thromboembolic condition
● lasts about 1.5 to 4 hours
● destroyed by an enzyme in the blood,
heparinase
■ Coumarin: Warfarin
● decreases liver production and lessens number
of of Active prothrombin and Factors VII, IX, X
in plasma and stores
 ● inhibits enzyme: Vitamin K epoxide reductase
complex I (VKOR c1): enzyme converts inactive
vitamin K to active
● over several days, stores of active coagulation
factors degrade and replaced by inactive
● after administration, coagulant activity of blood
effects
○ 12 hours: ↓ about 50%
○ 24 hours: ↓ about 20%
● Normal coagulation returns 1-3 days
discontinuing coumarin therapy

1. Ethylenediaminetetraacetic acid (EDTA)

=(Lavender top)
=Chelates calcium
=Inversion: 8x
=Anticoagulant of choice for hematology cell counts and
cell morphology
=Blood smear: prepare w/in 2 hrs
=Preferred anticoagulant for platelet count:
= In some patients w/ EDTA anticoagulated blood – platelet
satellitism
= Platelet satellitism: platelets adhere to neutrophils
♫ Effect to automated platelet count Decreased
♫ Remedy: Repeat platelet count using citrate (Rodak:
Platelet count x 1.1)
EDTA = Shrinkage of cells = Hct = ESR
Not for coagulation tests:
= Inhibits fibrinogen-thrombin reaction
= Factor V is not stable in EDTA
2. Heparin
=( Green Top )
​ =Inactivation of thrombin
​ =Anticoagulant for osmotic fragility test
=Inversion: 3-4x
=Not for blood film preparation:
= Distorts cells
= Produces bluish background on Romanowsky’s stain
=Not for coagulation
​ = Inhibits thrombin and all stages of coagulation

3. Sodium Citrate (3.2%)

=(Light blue top tube)
​= chelates calcium
=For coagulation and platelet studies
= Preserves labile factors V and VIII
= Buffered 3.2% (0.109M) citrate
=Inversion: 3-4x
=Ratio = 1:9 (Anticoagulant-to-Blood)

●
●
●
●
●
●
●
●
●
●
●
●
●
 ● Adaptive Immunity

A. Definitions
1. Immunity is the processes that occur to defend the body against
foreign organisms or molecules.
2. Immunity includes:a. Inflammation
b.Complement activation
c. Phagocytosis
d. Antibody synthesis
e.Effector T lymphocyte
B. Types of Immunity

1. Innate (nonspecific or natural)

a. Born with it, do not need prior exposure

b. The effectiveness of the immune response varies with age.
c. First line of defense: ​Designed to keep microorganisms out

1)​ Physical barriers​, such as epithelial cells (intact skin), trapping of

bacteria in mucus, etc.
2)​ Chemicals ​secreted by cells and tissues, such as acidic pH of skin
surface, complement, interferons, lysozymes, etc.

d. Second line of defense

1)​ Phagocytosis:​ The process of a white blood cell (WBC) engulfing
bacteria
2) ​Inflammation​: Nonspecific response to tissue damage that includes
a) Chemical release
b) Cellular movement
c) Elimination of foreign material
d) Tissue repair
3) ​Complement system​: Enhances phagocytosis, stimulates
inflammatory response, and lyses foreign cells
2.​ Adaptive (specific or acquired)
a. Acquired only after a specific challenge is encountered and
responds specifically to the challenge
b. Two responses:

1) Humoral-mediated immunity (HMI)

a) More important in protection against extracellular pathogens
b) Antibody production by plasma cells
2) Cell-mediated immunity (CMI)
a) More important in protection against intracellular pathogens
b) Natural killer (NK) cells: Some activity against tumor cells
c) T helper cells
d) Cytotoxic T lymphocytes (CTLs)
e) Cytotoxins

c. Active immunity
-​ generally endures for life
1) Natural​: The host is exposed to foreign immunogen as a result of
infection, and the host's immune cells manufacture specific products to
eliminate foreign immunogen.
2) ​Artificial: Vaccination; immune system responds to an altered
(noninfectious) organism
.
d. Passive immunity
-​ short term; no memory cells produced
1) ​Natural​: Maternal antibody crosses placenta to protect infant
2)​Artificial: Immune products from another animal injected into the
host (e.g., pooled gamma-globulin)
● Conditions That Cause Excessive Bleeding in Humans
Bleeding caused by :
1. Vitamin K deficiency
can cause decreased in the 5 important clotting factors:
● Prothrombin
● Factor VII
● Factor IX
● Factor X
● Protein C
*Vitamin K is an essential factor to a liver carboxylase that
adds a carboxyl group to glutamic acid residues on the
important clotting factors
*One of the most prevalent causes of Vitamin K def is failure
of the liver to secrete bile into the gastrointestinal tract
2. Hemophilia
● is bleeding disease that occurs almost exclusively in
males
● 85% is caused by an abnormality or deficiency of
Factor VIII; this type of hemophilia is called
Hemophilia A or Classic Hemophilia.
● 15% bleeding is caused by deficiency of Factor IX
 ● Both factors are transmitted genetically by way of
female chromosome
3. Thrombocytopenia
● means the presence of very low numbers of platelets
in the circulating blood
● bleeding is usually from many small venules or
capillaries rather than from larger vessels as in
hemophilia.
● it results to small punctuate hemorrhages occur
throughout all the body tissues
● the skin of such a person displays many small ,
purplish blotches, giving the disease the name
“Thrombocytopenic Purpura”
● bleeding will not occur until the number of platelets
falls below 50,000/uL
○ normal is 150,00-300,000
○ levels as low as 10,000/uL are frequent lethal
● can suspect the existence of thrombocytopenia if the
person’s blood clot fails to retract
● most people with thrombocytopenia have the disease
known as Idiopathic Thrombocytopenia (for
unknown reasons antibodies have formed and react
against the platelets to destroy them)

1. Vitamin K deficiency, Hemophilia, Thrombocytopenia

2. Decrease Prothromin, Factor VII, Factor IX, caused by
Vitamin K deficiency
3. Blood clotting factors – formed in liver
4. Disease state – hepatitis, cirrhosis, acute yellow atrophy
(degeneration of liver – toxins, infections, etc.)
5. Depressed formation of clotting factors in the liver –
Vitamin K deficiency
 6. Vitamin K – essential factor – to a liver carboxylase that
adds a carboxyl group to glutamic acid residue on five of
more important clotting factors - VII, IX, X, and protein C
7. Addition of carboxyl group to glutamic acid – vitamin K is
oxidized and becomes inactive
8. Enzyme – vitamin K epoxide reductase complex 1 VKOR c1
– reduce vitamin K back to active form
9. Absence of active vitamin K – insufficiency in coagulation
factors – extreme bleeding tendencies
10. Vitamin K – synthesized by intestinal bacteria
11. GI disease – vitamin K deficiency – poor absorption of
fats
12. Prevalent cause of deficiency – failure of liver to secrete
bile in GIT – obstruction of bile duct
13. Lack of bile prevents adequate f
14. Liver disease – decrease production of prothrombin and
other factor

As a result, vitamin K is injected into surgical patients with liver

disease or with obstructed bile ducts before the surgical procedure is
performed. Ordinarily, if vitamin K is given to a deficient patient 4 to
8 hours before the operation and the liver parenchymal cells are at
least one-half normal in function, sufficient clotting factors will be
produced to prevent excessive bleeding during the operation.

●
●
●
 ●
● Hemophilia
● Abnormality or deficiency of factor VIII – hemophilia A ;
classic hemophilia
● 15% - hemophilia B – factor IX deficiency
● Transmitted – female chromosome
● No hemophilia in females – one of X chromosomes has
appropriate genes, the other one is a carrier
● Von Willebrand disease – loss of the large component
● Injection of purified Factor VIII
● Thrombocytopenia
● Thrombocytopenia – low numbers of platelet in circulating
blood
● Tendency to bleed – usually from small venules or capillaries
● Thrombocytopenic purpura – many small, purplish blotches
● Bleeding occurs if platelet falls below 50,000/uL
● 10,000/uL – fatal
● Clot retraction – dependent on release of multiple coagulation
factors from the large numbers of platelets entrapped in the
fibrin mesh of the clot
● Idiopathic thrombocytopenia
● TX – transfusion of fresh whole blood
● Splenectomy but may cause large number of platelets

●
●
●
●
●
●
●
●
●
 ● A-O-B Blood Type
ABO AND H BLOOD GROUP SYSTEMS AND SECRETOR STATUS
A​. Landsteiner's Rule​: If an individual has the antigen, that
individual will not have the antibody. This is a universal law and
has few exceptions.

B​. ABO Antigens

​1. Found on RBCs, lymphocytes, platelets, tissue cells, bone
marrow, and organs
2. These antigens can be secreted by tissue cells if the
appropriate genes are present.
3. Glycolipid or glycoprotein
4. Developed in utero at 5-6 weeks of gestation
5. Full expression of ABO antigens occurs between 2 and 4 years
of age.

C​. Inheritance and Development of A, B, and H Antigens

1 . The H antigen is the building block for the A and B antigens.
There are only
two alleles in the H gene: H and h. The H allele is found in 99.99%
of the
world's population, and h is a rare amorph allele.
2. The H antigen acts as the acceptor molecule for the two sugars
that make up the A and B antigens.
3. The A blood type is the H antigen with A^-acetylgalactosamine
attached.
4. The B blood type is the H antigen with o-galactose attached.
5. The O blood type is the H antigen with no additional sugar
attached.
 BLOOD BANK REAGENTS AND METHODS
A.​ Principle of Blood Bank Tests
Ag + Ab <-» Ag-Ab reaction
B.​ Routine Blood Bank Testing Procedures
1.​ ABO/Rh typing
a. Detects A, B, and D an
b. Source of antigens: Patient's RBCs (forward grouping/typing);
reagent
RBCs (reverse grouping)
c. Source of antibodies: Reagent anti-A, anti-B, and anti-D
(forward
grouping/typing); patient's serum (reverse grouping)

2​. Antibody screen

a. Detects specific antibodies to RBC antigens
b. Source of antigens: Reagent antibody screening cells
c. Source of antibodies: Patient's serum
3.​ Antibody identification
a. Identifies antibodies to RBC antigens
b. Source of antigens: Reagent antibody panel cells (10-16 cells)
c. Source of antibodies: Patient's serum
4. ​Crossmatch
a. Determines compatibility of donor RBCs with recipient's blood
b. Source of antigens: Donor cells
c. Source of antibodies: Recipient's serum
1. Two antigens – type A and type B
2. Antigens = agglutinogens – inherited
3. Major OAB
Genotypes Blood types Agglutinog Agglutinins -
ens antibody
OO O None Anti-A, Anti-B
OA, AA A A Anti-B
OB, BB B B Anti-B
AB AB A and B None

4. Genetic Determination
a. Three alleles
b. I​A​, I​B​, I​O
c. I = immunoglobulin
 d. O allele – recessive
e. A and B alleles – codominant
5. Relative Frequencies
a. O = 47%
b. A = 41%
c. B = 9%
d. AB = 3%
6. Agglutinins
a. Type A agglutinogen is not present – antibodies known as
anti-A agglutinins develop in plasma
b. Type B agglutinogen is not present – antibodies known as
anti-B agglutinins develop in plasma
c. Type A = Type A agglutinogen, Anti-B agglutinins
d. Type B = Type B agglutinogen, Anti-A agglutinins
7. Titer
a. 2-8 months
b. Changes titers of the anti-A and anti-B agglutinins at
different age

c. Max titer = 8-10 years old

d. Gradually decline
8.
9.
10. Origin
a. Agglutinins = gamma globulins – bone marrow and lymph
gland
b. IgM and IgG
c. Small amounts of antigens enter the food, bacteria, and in
other ways
11. Agglutination Process
a. Because the agglutinins have 2 binding sites (IgG type) or
10 binding sites (IgM type), a single agglutinin can attach to
two or more RBCs at the same time, thereby causing the
cells to be bound together by the agglutinin.
b. This binding causes the cells to clump, which is the process
of “agglutination.”
c. Then these clumps plug small blood vessels throughout the
circulatory system.
d. During ensuing hours to days, either physical distortion of
the cells or attack by phagocytic white blood cells destroys
the membranes of the agglutinated cells, releasing
hemoglobin into the plasma, which is called hemolysis of
the RBCs.
12. Acute Hemolysis
a. Immediate hemolysis – antibodies cause RBC lysis by
activating the complement – release of proteolytic enzymes
that rupture cell membranes
b. Immediate intravascular hemolysis – less common than
agglutination followed by delayed hemolysis
c. Different antibody type – IgM – hemolysins
13. Blood Typing
a. Blood typing and matching
b. RBC separated from plasma, then diluted by saline.
c. Other portion is mixed with anti-A agglutinin and other is
anti-B agglutinin
d. Mixture observed in microscope
 e. If RBC is agglutinated – antibody-antigen reaction has
resulted

● Transfusion Reaction
A. Donor’s blood is agglutinated
a. Rare that transfuse cells cause agglutination of
recipient’s blood
b. Plasma portion of donor blood immediately becomes
diluted by all the plasma
c. The small amount of infused blood does not
significantly dilute the agglutinins in the recipient’s
plasma.
d. Therefore the recipient’s agglutinins can still
agglutinate the mismatched donor cells
B. Jaundice
a. Hemolysis – hemoglobin release – phagocytes
converts hemoglobin to bilirubin
b. Yellow discoloration of skin
c. 400 mL of blood are hemolysed in less than a day
C. Acute kidney failure after transfusion reaction
a. Few minutes to few hours
b. Ab-Ag reaction release toxic substance from
hemolysing blood – powerful renal vasoconstriction
c. Loss of circulating RBC, along with the production of
the toxic substance from hemolyzed cells and AbAg
complex – CIRCULATORY SHOCK
i. Arterial blood flow is very low
ii. Renal blood flow and urine output is decerease
d. Total amount of free hemoglobin released into the
circulating blood is greater than the quantity that can
bind to haptoglobin – If high small percentage can be
absorbed in the tubular epithelium. Yet water
continues to be reabsorbed, causing the tubular
hemoglobin concentration to rise so high that the
hemoglobin precipitates and block many kidney
tubules.
e. Renal vasoconstriction, circulatory shock, renal
tubular blockage – acute renal shutdown
f. Not resolved patient dies within 12 days