complete answers to reviewer for physio

8/2/2019 Complete Answers to Reviewer for Physio

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REVIEWER FOR REMOVAL EXAMS

1. Correlate the composition of the cell membrane with the mode of transport of polar and non-polar substances into the cell.

Diffusion through the cell membrane is divided into two subtypes called simple and facilitated

diffusion. Simple diffusion means that kinetic movement of molecules or ions occurs through the cell

membrane by two pathways: (1) through the interstices of the lipid bilayer if the diffusing substance is

lipid soluble, and (2) through watery channels that penetrate all the way through some of the large

transport proteins. Facilitated diffusion is also called carrier-mediated diffusion because a substance

transported in this manner diffuses through the membrane using a specific carrier protein to help. That

is, the carrier facilitates diffusion of the substance to the other side.

Enough water ordinarily diffuses in each direction through the red cell membrane per second to

equal about 100 times the volume of the cell itself. Yet, normally, the amount that diffuses in the two

directions is balanced so precisely that zero net movement of water occurs. Therefore, the volume of

the cell remains constant. However, under certain conditions, a concentration difference for water can

develop across a membrane, just as concentration differences for other substances can occur. When this

happens, net movement of water does occur across the cell membrane, causing the cell either to swell

or to shrink, depending on the direction of the water movement. This process of net movement of watercaused by a concentration difference of water is called osmosis.

Active transport is divided into two types according to the source of the energy used to cause

the transport: primary active transport and secondary active transport. In primary active transport, the

energy is derived directly from breakdown of adenosine triphosphate (ATP) or of some other high-

energy phosphate compound. In secondary active transport, the energy is derived secondarily from

energy that has been stored in the form of ionic concentration differences of secondary molecular or

ionic substances between the two sides of a cell membrane, created originally by primary active

transport. In both instances, transport depends on carrier proteins that penetrate through the cell

membrane, as is true for facilitated diffusion. However, in active transport, the carrier protein functions

differently from the carrier in facilitated diffusion because it is capable of imparting energy to the

transported substance to move it against the electrochemical gradient. Following are some examples ofprimary active transport and secondary active transport, with more detailed explanations of their

principles of function. Different substances that are actively transported through at least some cell

membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions,

iodide ions, urate ions, several different sugars, and most of the amino acids.

2. Describe the events and pathways from initial antigen contact to eventual antibodyproduction and T-cell activation.

Within minutes after inflammation begins, the macrophages already present in the tissues,

whether histiocytes in the subcutaneous tissues, alveolar macrophages in the lungs, microglia in the

brain, or others, immediately begin their phagocytic actions. When activated by the products of

infection and inflammation, the first effect is rapid enlargement of each of these cells. Next, many of the

previously sessile macrophages break loose from their attachments and become mobile, forming the

first line of defense against infection during the first hour or so.

Within the first hour or so after inflammation begins, large numbers of neutrophils begin to invade

the inflamed area from the blood. This is caused by products from the inflamed tissues that initiate the

following reactions: (1) They alter the inside surface of the capillary endothelium, causing neutrophils to

stick to the capillary walls in the inflamed area. This effect is called margination. (2) They cause the


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intercellular attachments between the endothelial cells of the capillaries and small venules to loosen,

allowing openings large enough for neutrophils to pass by diapedesis directly from the blood into the

tissue spaces. (3) Other products of inflammation then cause chemotaxis of the neutrophils toward the

injured tissues, as explained earlier. Thus, within several hours after tissue damage begins, the area

becomes well supplied with neutrophils. Because the blood neutrophils are already mature cells, they

are ready to immediately begin their scavenger functions for killing bacteria and removing foreign

matter. Also within a few hours after the onset of acute, severe inflammation, the number of

neutrophils in the blood sometimes increases fourfold to fivefold from a normal of 4000 to 5000 to

15,000 to 25,000 neutrophils per microliter. This is called neutrophilia, which means an increase in the

number of neutrophils in the blood.

Along with the invasion of neutrophils, monocytes from the blood enter the inflamed tissue and

enlarge to become macrophages. However, the number of monocytes in the circulating blood is low:

also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils.

Therefore, the buildup of macrophages in the inflamed tissue area is much slower than that of

neutrophils, requiring several days to become effective. Furthermore, even after invading the inflamed

tissue, monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and

develop tremendous quantities of lysosomes; only then do they acquire the full capacity of tissuemacrophages for phagocytosis. Yet, after several days to several weeks, the macrophages finally come

to dominate the phagocytic cells of the inflamed area because of greatly increased bone marrow

production of new monocytes, as explained later. As already pointed out, macrophages can phagocytize

far more bacteria (about five times as many) and far larger particles, including even neutrophils

themselves and large quantities of necrotic tissue, than can neutrophils.

The fourth line of defense is greatly increased production of both granulocytes and monocytes by

the bone marrow. This results from stimulation of the granulocytic and monocytic progenitor cells of the

marrow. However, it takes 3 to 4 days before newly formed granulocytes and monocytes reach the

stage of leaving the bone marrow. If the stimulus from the inflamed tissue continues, the bone marrow

can continue to produce these cells in tremendous quantities for months and even years, sometimes ata rate 20 to 50 times normal.

Although more than two dozen factors have been implicated in control of the macrophage response

to inflammation, five of these are believed to play dominant roles. They consist of (1) tumor necrosis

factor (TNF), (2) interleukin-1 (IL-1), (3) granulocyte-monocyte colony-stimulating factor (GM-CSF), (4)

granulocyte colony-stimulating factor (G-CSF), and (5) monocyte colony-stimulating factor (M-

CSF).These factors are formed by activated macrophage cells in the inflamed tissues and in smaller

quantities by other inflamed tissue cells. The cause of the increased production of granulocytes and

monocytes by the bone marrow is mainly the three colony-stimulating factors, one of which, GM-CSF,

stimulates both granulocyte and monocyte production; the other two, G-CSF and M-CSF, stimulate

granulocyte and monocyte production, respectively. This combination of TNF, IL-1, and colony-

stimulating factors provides a powerful feedback mechanism that begins with tissue inflammation and

proceeds to formation of large numbers of defensive white blood cells that help remove the cause of

the inflammation.

When neutrophils and macrophages engulf large numbers of bacteria and necrotic tissue, essentially

all the neutrophils and many, if not most, of the macrophages eventually die. After several days, a cavity

is often excavated in the inflamed tissues that contains varying portions of necrotic tissue, dead

neutrophils, dead macrophages, and tissue fluid. This mixture is commonly known as pus. After the


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infection has been suppressed, the dead cells and necrotic tissue in the pus gradually autolyze over a

period of days, and the end products are eventually absorbed into the surrounding tissues and lymph

until most of the evidence of tissue damage is gone.

3. Describe the volume and pressure changes in the different thoracic compartments duringinspiration and expiration.

Pleural pressure is the pressure of the fluid in the thin space between the lung pleura and the chest

wall pleura. The normal pleural pressure at the beginning of inspiration is about 5 centimeters of

water, which is the amount of suction required to hold the lungs open to their resting level. Then, during

normal inspiration, expansion of the chest cage pulls outward on the lungs with greater force and

creates more negative pressure, to an average of about 7.5 centimeters of water. Alveolar pressure is

the pressure of the air inside the lung alveoli. during normal inspiration, alveolar pressure decreases to

about1 centimeter of water. This slight negative pressure is enough to pull 0.5 liter of air into the lungs

in the 2 seconds required for normal quiet inspiration. During expiration, opposite pressures occur: The

alveolar pressure rises to about +1 centimeter of water, and this forces the 0.5 liter of inspired air out of

the lungs during the 2 to 3 seconds of expiration. The transpulmonary pressure is the pressure

difference between that in the alveoli and that on the outer surfaces of the lungs, and it is a measure ofthe elastic forces in the lungs that tend to collapse the lungs at each instant of respiration, called the

recoil pressure.

The extent to which the lungs will expand for each unit increase in transpulmonary pressure (if

enough time is allowed to reach equilibrium) is called the lung compliance. The total compliance of both

lungs together in the normal adult human being averages about 200 milliliters of air per centimeter of

water transpulmonary pressure. That is, every time the transpulmonary pressure increases 1 centimeter

of water, the lung volume, after 10 to 20 seconds, will expand 200 milliliters.

4. Define the different lung volumes. Give the approximate values in adults for Tidal Volume,Residual Volume, Vital Capacity and anatomic dead space.

The air in the lungs has been subdivided into four volumes and four capacities, which are average

for a young adult man. The four listed pulmonary lung volumes, when added together equal the

maximum volume to which the lungs can be expanded. The Tidal volume is the volume of air inspired or

expired with each normal breath; it amounts to 500 milliliters in the adult male. The Inspiratory reserve

volume is the extra volume of air that can be inspired over and above the normal tidal volume when the

person inspires with full force. The Expiratory reserve volume is the maximum extra volume of air that

can be expired by forceful expiration after the end of a normal tidal expiration after the end of a normal

tidal expiration. The residual volume is the volume of air remaining in the lungs after the most forceful

expiration; this volume averages about 1200 milliliters.

When two or more volumes are considered, such combinations are called pulmonary capacities.

These can be described as Inspiratory capacity which equals the tidal volume plus the inspiratory reserve

volume; Functional residual capacity which equals the expiratory reserve volume plus residual volume;

Vital capacity, which equals the inspiratory reserve volume plus the tidal volume plus the expiratory

reserve volume, is about 4600 molliliters; and Total lung capacity, which is the maximum volume which

lungs can be expanded with the greatest effort, is equal to the vital capacity plus the residual volume.

The anatomic dead space is the volume of all the space of the respiratory system other than the

alveoli and their other closely related gas exchange areas. This space equals 1 to 2 liters.


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5. Define compliance in the lungs and correlate it with surfactant.Compliance refers to the extent to which the lungs will expand for each unit increase in

transpulmonary pressure. If there is an increase in volume there would also be an increase in pressure.

Transpulmonary pressure refers to the difference in pressure between the alveoli and the outer surface

of the lings and is measured by the elastic forces in the lungs. There are two elastic forces in lungs: (1)

elastic forces of the lung tissue and (2) the elastic forces caused by the surface tension of the fluid that

lines the inside walls of the alveoli and other lungs spaces. When the lungs are fillled with air, there is an

interface between the alveolar fluid and the air in the alveoli. Surface tension is formed when the water

forms a surface in with air, the water molecules will exert strong attraction for one another causing

these molecules to contract for them to hold together. In the case of the surface tension in the alveoli,

the walls of the alveoli are coated with thin film of water. These water molecules are more attracted

with each other than to air creating a surface tension. This tension increases as the water molecules

come closer together which what happens when we exhale wherein our alveoli become smaller (like a

deflating balloon). The water molecules will contract forcing the air out thus causing the alveoli to

collapse. If this occurs the lungs would have difficulty to re-expand when you inhale. The role of

surfactants in the lungs is to reduce the fluid-air surface tension to allow the lungs to expand fully when

we inhale. Surfactants are produced by the type II alveolar epithelial cells, this is a surface active agentwhich functions to reduce the surface tension of water. It is composed of several phospholipids with

hydrophobic tails. The hydrophobic tails comes closer together during expiration causing a decrease in

surface tension (stage 3-5 in the picture). They move further apart when the alveoli expand. When you

exhale, they prevent the water molecules (phospholipids= not soluble to water) to come closer thus

decreasing the surface tension.

Remenber in the law of laplace (see formula below) states that the pressure within a sphecial

structure with surface tesion is inversely proportional to the radius of the sphere. Hence, small radius

(smaller alveoli) will generate bigger pressures with them than that of larger alveoli. Smaller alveoli

would therefore be expected to empty into larger alveoli as lung volume decreases. This does not occur,

however, because surfactant differentially reduces surface tension, more at lower volumes and less at

higher volumes, leading to alveolar stability and reducing the likelihood of alveolar collapse. Smaller

alveoli would therefore be expected to empty into larger alveoli as lung volume decreases. This does notoccur, however, because surfactant differentiallyreduces surface tension, more at lower volumes and

less at higher volumes, leading to alveolar stability and reducing the likelihood of alveolar collapse.


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6. Describe how oxygen and carbon dioxide are transported in the lungs and in tissues.

Oxygen is not very soluble in plasma. Most oxygen (about 97% of it) is transported via hemoglobin,

which has special oxygen-binding capabilities. You would want it to bind to significant quantities of

oxygen at the alveolar level, even when oxygen concentration in the alveoli is relatively low. You would,

on the other hand, also like hemoglobin to release oxygen easily at the tissue level, but in just the right

amounts, since too much can cause oxygen toxicity, and too little will not provide enough for the

respiratory needs of the tissue. You would like hemoglobin to release large quantities of oxygen when

the tissues really need it. Considering the oxygen dissociation curve, however, note that if alveolar pO2

levels fall really low, particularly below 40 (example at an altitude of 20,000ft or in condition where

adequate amounts of oxygen do not reach the alveoli) hemoglobin will falter in trapping o2 and the

patient will go downhill.

Hemoglobin does not transport most of the carbon dioxide. Rather, CO2 combines with water in the RBC

to form H2CO3 (the enzyme carbonic anhydrase in the RBC catalyzes this reaction). The H from the

H2CO3 combines with the hemoglobin; HCO3 leaves the call and floats around in the blood until the

blood reaches the lungs. Then the hemoglobin releases the H, which combines with bicarbonate ion to

reform CO2, which is then expelled by the lungs. Some CO2 does, however, combine directly with

hemoglobin (about 25%) to form carbaminohemoglobin, which releases its CO2 in the lungs.

Additionally, a small amount of CO2 (about 5%) dissolves directly in the plasma.

7. Explain how breathing is regulated by pO2 and pCO2

Moderate increase of pCo2 stimulates respiration much more than does a moderate decrease in pO2.Moderate increases in pCO2 results in increased respiratory rate, without requiring much assistance

from the stimulus of decreased O2. However, in severe pulmonary disease, in which there is poor

exchange in both o2 and CO2, the CO2 effect is not enough. The large drop in PO2 then comes into play

having a marked effect in increasing the rate of respiration when the PO2 falls to the 30-60mmHg range.

8. Compare the changes in membrane potential associated with an associated in a nodal pacemaker

cell with those in a myocardial cell. What (mechanism/s) is/are responsible for such changes in

membrane potential?

Cardiac Action PotentialThe resting membrane potential is determined by the conductance to potassium and approaches the

potassium equilibrium potential. Inward current brings positive charge into the cell and depolarizes the

membrane potential. Outward current takes positive charge out of the cell and hyperpolarizes the

membrane potential. The role of the sodium-potassium ATPase is to maintain ion gradients across the

cell membrane


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Mechanism of Ca extrusion

Na-Ca ExchangerNa in then Ca out; 3Na:1Ca, higher concentration

Na-K-ATPase pump lower concentration, Na concentration gradient outside the cell goes inside

Ca pump strength of the muscular contraction is determined by the amount of Ca which interacts with

the myofilament, Ca remains in the cell

Increase Ca=Increase contraction = Increase cardiac performance

9. Discuss how a ventricular action potential develops. What changes occur in terms of: 1) membrane

permeability, 2) ionic fluxes and 3) membrane potential? How do these changes come about? How is

the development of a pacemaker potential any different from the development of a ventricular action

potential?

SLOW-RESPONSE ACTION POTENTIAL

-SA node (normally the pacemaker of the heart)

-does not have a constant resting potential

-exhibits phase 4 depolarization of automatically due to:

--gradual decrease in the permeability of membrane to potassium, therefore sodium is prevented from

leaking out

--increase in the permeability to sodium, therefore sodium moves into the cell; Na-K permeability ratio

increases; membrane potential approaches a more positive value

--increase permeability to calcium; net movement it towards the cell

PHASES:

Phase 0-upstroke of action potential = increase Ca

Phase 3-repolarization = increase in KPhase 4-slow depolarization = increase Na

Phases 1&2 are not present

FAST-RESPONSE ACTION POTENTIAL

-atrial muscle, purkinje fibers, ventricular muscle

-have a stab;e resting membrane potential of about 90mV which approaches the potassium equilibrium

potential

-action potential are of long duration (200-300 milliseconds)

PHASES:

Phase 0-rapid upstroke = influx NaPhase 1-initial repolarization = efflux K

Phase 2-plateau = slow Ca channels are opened so influx Ca

Phase 3-repolarization = Ca channels close but permeable to sodium so influx of Na

Phase 4-resting membrane potential = inward and outward currents are equal


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*questions 8 & 9 is a bit confusing. If you find it wrong, please catch my attention and feel free to correct it. -bebe

10. CARDIAC CYCLE

- Initiated by the action potential in the sinus node, traveling rapidly through both atria and then

through the AV bundle into the ventricles.

- Total duration of the cardiac cycle is reciprocal of heart rate

ex: HR= 72 beats/min; Cardiac cycle=1/72 beats/min

therefore, an increase in heart rate, is a decrease in Cardiac cycle


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PERIOD I: FILLING OF VENTRICLES DURING DIASTOLE

Ventricular Systole

AV valves are closed that will give large amounts of blood accumulating in both atria

P wave (depolarization in atria)

Slight rise in ATRIAL PRESSURE will push AV valves open

VENTRICULAR PRESSURE will fall

Rapid blood flow to ventricles will increase VENTRICULAR VOLUME

PERIOD II: PERIOD OF ISOVOLUMIC (ISOMETRIC) CONTRACTION

Increase in tension but no shortening of muscle fiber Period of contraction but no emptying

QRS wave (depolarization in ventricles) and

1st Heart Sound (low pitch, long lasting)

Ventricles contract

Increase VENTRICULAR PRESSURE

AV valves close

Semilunar valves open

PERIOD III: EJECTION

Blood pours out of ventricles

1st

(Rapid ejection) 2nd

(Slow ejection)

Decrease in VOLUME


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PERIOD IV: PERIOD OF ISOVOLUMIC (ISOMETRIC) RELAXATION

T wave (Repolarization of Ventricles) and

Ventricular Diastole

Decrease in VENTRICULAR PRESSUREVOLUME is same

2nd Heart Sound

Pulmonary valves close

AV valves open


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11. FACTORS AFFECTING MYOCARDIAL OXYGEN CONSUMPTION (MVO2).

A. Increase MVO2: Increase in Heart Rate, Inotropy, Afterload, Preload.

HR = because myocytes are generating twice the number of tension cycles per minute.

INOTROPY = because both the rate of tension development and the magnitude of tension are increased,

and they both are associated with increased ATP hydrolysis and oxygen consumption.

AFTERLOAD = because it increases the tension that must be developed by myocytes.

PRELOAD = Increasing stroke volume by increasing preload (end-diastolic volume)

B. IN A NORMAL HEART, HOW WOULD CHANGES IN THESE FACTORS AFFECT CORONARY BLOOD

FLOW?

Coronary blood flow is phasic as determined by systole and diastole. Left coronary flow decreases during

systole and reaches a peak early in diastole. Under resting conditions, coronary venous blood containslittle oxygen, and increased myocardial oxygen consumption must be met by increased coronary blood

flow.

12. WHY IS TETANUS OF CARDIAC MUSCLE IMPOSSIBLE? WHY IS THIS ADVANTAGEOUS?

A long refractory period prevents tetanus in cardiac muscle. The long refractory period means that

cardiac muscle cannot be restimulated until contraction is almost over & this makes summation (&

tetanus) of cardiac muscle impossible. This is a valuable protective mechanism because pumping

requires alternate periods of contraction & relaxation; prolonged tetanus would prove fatal.

13. What are the factors that affect cardiac output?

Before we talk about that, let's define what cardiac output is. Cardiac output is the volume of

blood ejected by the left and right ventricle.

STROKE VOLUME x HEART RATE = CARDIAC OUTPUT / (SV x HR = CO)

STROKE VOLUME - measuring the volume of blood present within the left ventricle just prior to

contraction and measuring the volume of blood present after the full contraction is complete

The factors that affect the cardiac output are the following:


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1. Contractility - the more the heart contracts, the more blood gets pumped per beat, increasing stroke

volume and cardiac output; higher contractility will result to an increase in cardiac output

2. Preload- filling of the heart chambers with a certain amount of blood right BEFORE it contracts; "end

diastolic volume"; An increase in the filling of heart chambers with blood would increase the stretching

of the cardiac muscle fibers as well as the stroke volume

3. Afterload - pressure the heart must overcome to eject the blood into the rest of the body; "mean

arterial pressure". A change in pressure could affect the cardiac performance so when the aortic

pressure increases, the stroke volume decreases.

14. Discuss the short-term regulation of blood pressure.

BLOOD PRESSURE = CARDIAC OUTPUT x PERIPHERAL RESISTANCE

Short term control of Blood pressure is mediated by the nervous system, chemicals and hormones that

control blood pressure by changing peripheral resistance. ( = in sec / minutes)

a. Nervous system: Control blood pressure by changing blood distribution in the body and by changing blood

vessel diameter. ANS sympathetic veins, arteries, heart control HR and force of contraction

Parasympathetic

The vasomotor center is a cluster of sympathetic neurons found in the medulla. It sendsefferent motor fibers that innervate smooth muscle of blood vessels. Any increase in

sympathetic activity causes vasoconstriction and any decreased sympathetic activity leads to

vasodilation.

Baroreceptors are stretch receptors found in the carotid body, aortic body and the wall of alllarge arteries of the neck and thorax.

When BP activation of baroreceptorssend impulses (APs) to the vasomotorcenter inhibition of vasomotor center

parasympathetic

activity HR

sympathetic activity

force of contraction and HR

vasodilation of arteries and veins

peripheral resistance and vessel diameter

CO and PR Blood Pressure


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When BP inhibition of baroreceptorssend impulses (APs) to the vasomotorcenter activation of vasomotor center

There is dual regulation by both sympathetic and parasympathetic to control a rise in BP. The baroreflex is the fastest regulation method for blood pressure.b. Chemoreceptors: these respond to changes in pCO2 and pO2 and PH levels.

When pO2 and PH and pCO2 Stimulation of vasomotor center CO andHR and vasoconstrictionBP (speeding return of blood to the heart and lungs)

c. Hormones: bloodborne chemicals

Adrenal Medulla Hormones (epinephrine & norepinephrine) When the body is stressed, adrenal medulla releases NE and E into the blood

enhance sympathetic activity.

NE vasoconstriction E CO and HR (it also promotes generalized vasoconstriction except in skeletal

and cardiac muscle where it causes vasodilation)

Atrial Natriuretic Peptide (ANP) Produced by heart atrium Natri release of Na+ Uretic excretion of urine It promotes the excretion of Na+ from the body water also is excreted Blood

Volume Blood Pressure.

Antidiuretic Hormone (ADH) Decrease the excretion of water Leads to blood volume BP.

Endothelial factors Local system in the blood vessel endothelium

sympathetic activity

force of contraction and HR

vasoconstriction of arteries and veins

peripheral resistance and vessel diameter

parasympathetic

activity HR

CO and PR Blood Pressure


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Release of endothelin vasoconstriction NO Nitric Oxide vasodilation NO works for a small time only because it is quickly destroyed. Represents fine minute regulation at the tissue level

15. Discuss the factors that affect fluid flow in rigid tubes.

The factors that affect fluid flow are distensibility of the blood vessels, pressure and constant flow.

Flow

Flow is more likely to be turbulent if:

Velocity is highViscosity of blood is lowBlood vessel diameter is highThe conditions for turbulence are summarised in the Reynolds Number

Note that turbulent flow is noisy and will give rise to sounds or murmurs

In turbulent flow, the resistance to flow is increased

Turbulent flow results in damage to endothelium

Distensibility and Pressure

Blood Vessels are not rigid

They are distensible especially so with veinsThey have blood inside them under pressureThey may have external pressures acting on themTransmural pressure = Pintravascular PextravascularWith a rigid tube, resistance is constant.

With a distensible tube, an increase in pressure stretches walls lowering resistance:

tendency for resistance to fall with increasing pressure

16. DISCUSS THE LOCAL AND EXTRINSIC CONTROLS THAT REGULATE ARTERIOLAR PRESSURE.

Local Control temperature; Heat application will dilate arterioles and cold application constricts them.

Extrinsic sympathetic control is important in regulating blood pressure Increased sympathetic activity

will lead to vasoconstriction, while decreased sympathetic activity will lead to arteriolar vasodilation.

If vasodilated decrease in pressure, and vice-versa if vasoconstricted.


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17. Discuss the factors the determine mean arterial pressure

a. Total Peripheral Resistance (TPA)Blood vessels provide resistance to the flow of blood because of friction between moving blood and

the wall of the vessel. The TPA refers to the sum total of vascular resistance to the flow of blood in the

systemic circulation. Because of their small radii, arterioles provide the greatest resistance to blood flow

in the arterial system. Adjustments in the radii of arterioles has a significant effect on TPA, which in turn

has a significant effect on MAP. Resistance and pressure are directly proportional to each other. If

resistance increases, then pressure increases. When the radii of arterioles decrease with

vasoconstriction, TPA increases, which causes MAP to increase.

b. Cardiac OutputCardiac output refers to the volume of blood pumped by the heart each minute. Put another way,

the cardiac output is a measure of blood flow into the arterial system. Blood flow is directly proportional

to pressure (Flow = pressure/resistance), therefore an increase in flow (cardiac output) will cause an

increase in pressure (MAP).

c. Blood VolumeBlood volume is directly related to blood pressure. If the blood volume is increased, then venous

return of blood to the heart will increase. An increase in venous return will, by Starling's Law, cause

stroke volume to increase. As stroke volume goes up the cardiac output goes up and the blood pressure

rises. Thus one way to control blood pressure over the long term is to control blood volume.

18. Describe the extrinsic and intrinsic innervation of the gastrointestina tract and explain their effects

on GI motility and secretion.

a. Intrinsic innervation:Myenteric Plexus/Auerbachs Plexus an outer plexus lyins between the longitudinal and

circular muscle layers

- not considered as excitatory since some of the neurons are

INHIBITORY; its inhiboitory signals are used for inhibiting the intestinal sphincter muscles that

impede food between segments of the g.i. tract, such as the pyloric sphincter, which controls

emptying of the stomach into the duodenum, and the sphincter of the ileocecal valve, which

controls emptying of the small intestine into the cecum.

Submucosal Plexus/Meissners Plexus an inner place that lies in the submucosa

- mainly concerned with controlling function within the inner wall

of each minute segment of the intestine; helps control local intestinal secretion, local

absorption, and local contraction of the submucosal muscle that cause various degrees of

infolding of the g.i. mucosa.

b. Extrinsic InnervationSympathetic the sympathetic nerve endings secrete mostly norepinephrine; stimulation

inhibits activity of the g.i. tract and exerts its effect in two ways: one, to a slight extent by direct

effect of the secreted norepinephrine to inhibit the smooth muscle and two, to a major extent


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by the inhibitory effect of the norepinephrine on the neurons of the enteric nervous system.

Hence, when sympathetic nerve fibers are stimulated, it can inhibit motor movements of the gut

to a point that it can block movement of food through the gastrointestinal tract.

Parasympatheticthe parasympathetic supply is divided into cranial and sacral divisions. The

cranial divisions are transmitted almost entirely in the vagus nerves which provide innervations

to the esophagus, stomach and pancreas, while the sacral divisions originate in the second,

third, and fourth sacral segments of the spinal cord and pass through the pelvic nerves to the

distal half of the large intestine.

19) Describe how peristalsis in the GI propels content analward.

Reflexes occur over considerable distances

(1) intestinointestinal overdistention in one segment causes relaxation in other

(2) ileogastric distention of ileum decreases gastric motility

(3) gastroileal gastric motility stimulates movement through ileocecal sphincter

Obstructions occur from cancer, ulcers, hernia, or paralytic ileus (loss of motility following abdominal

trauma or surgery)

*type of vomit indicates location above pylorus is acidic, below pylorus is basic

high obstruction produces intense vomiting, low obstruction leads to constipation and delayed vomiting

Emptying ileocecal sphincter is relaxed by ileal peristalsis, distention of terminal ileum, or gastroileal

reflex

Motility of the Colon

The colon absorbs water and electrolytes (in ascending colon), stores fecal matter, and

eliminates waste. Longitundinal muscle is gathered into three narrow bands (teniae coli)

two anal sphincters internal consists of smooth muscle, external of striated

Innervation parasymp. innervation is from the vagus nerve above transverse colon and from the pelvic

nerve below. Sympathetic decreases motility, parasymp. increases segmental movements and produces

sustained contractions

*external anal sphincter is innervated by somatic motor fibers both voluntary and reflex control

Haustration segments (haustra) mix and knead contents

Mass Movement periodic (1-3 per day) sustained contractions that move material forward

can be triggered by reflex from stomach (gastrocolic reflex) or duodenum (duodenalcolic reflex)

Defecation mass movement of feces into rectum causes internal sphincter relaxation and external

sphincter contraction


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*voluntary relaxation of external sphincter initiates defecation control of muscle is learned behavior

*if no motor nerves to external sphincter (babies or lower spinal damage), defecation is automatic upon

filling of rectum

20) Describe the regulation of gastric acid secretion.

Gastric acid is produced by parietal cells (oxyntic cells) in the stomach. The canaliculi, which

is an extensive secretory network of parietal cells (part of the epithelial fundic glands in the gastric

mucosa), secretes acid into the lumen of the stomach. The acidity is maintained by the H+/K+ ATPase

proton pump which allows parietal cells to release bicarbonate into the blood stream, which causes a

temporary rise in pH (alkaline tide). The resulting highly acidic environment in the stomach lumen

causes proteins from food to lose their characteristic folded structure (or denature). This exposes the

protein's peptide bonds. The chief cells of the stomach secrete enzymes for protein breakdown (inactive

pepsinogen and rennin). HCl activates pepsinogen into the enzyme pepsin, which then helps digestion

by breaking the bonds linking amino acids, a process known as proteolysis. Gastric acid production is

regulated by both the autonomic nervous system and several hormones. The parasympathetic nervous

system, via the vagus nerve, and the hormone gastrin stimulate the parietal cell to produce gastric acid,

both directly acting on parietal cells and indirectly, through the stimulation of the secretion of the

hormone histamine from enterochromaffine-like cells (ECL). Vasoactive intestinal peptide,

cholecystokinin, and secretin all inhibit production.

The production of gastric acid in the stomach is tightly regulated by positive regulators and

negative feedback mechanisms. Four types of cells are involved in this process: parietal cells, G cells, D

cells and enterochromaffine-like cells. Besides this, the endings of the vagus nerve (CN X) and theintramural nervous plexus in the digestive tract influence the secretion significantly. Nerve endings in

the stomach secrete two stimulatory neurotransmitters: acetylcholine and gastrin-releasing peptide.

Their action is both direct on parietal cells and mediated through the secretion of gastrin from G cells

and histamine from enterochromaffine-like cells. Gastrin acts on parietal cells directly and indirectly too,

by stimulating the release of histamine. The release of histamine is the most important positive

regulation mechanism of the secretion of gastric acid in the stomach. Its release is stimulated by gastrin

and acetylcholine and inhibited by somatostatin.

21) Explain how the gastric mucosal barrier protects the stomach.

Gastric Mucosal Barrier

The gastric mucosal barrier is the property of the stomach that allows it to contain acid.


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If the barrier is broken, as by acetylsalicylic acid (ASS, aspirin) in acid solution, acid diffuses back into the

mucosa where it can cause damage to the stomach itself.

The barrier consists of three protective components [1]. These provide the additional resistance for the

mucosal surface of the stomach. The three components include:

a compact epithelial cell liningo Cells in the epithelium of the stomach are bound by tight junctions that repel harsh

fluids that may injure the stomach lining.

a special mucus coveringo The mucus covering is derived from mucus secreted by surface epithelial cells and

mucosal neck cells. This insoluble mucus forms a protective gel-like coating over the

entire surface of the gastric mucosa. The mucus protects the gastric mucosa from

autodigestion by e.g. pepsin and from erosion by acids and other caustic materials that

are ingested.

bicarbonate ionso The bicarbonate ions are secreted by the surface epithelial cells. The bicarbonate ions

act to neutralize harsh acids.

Diagram of alkaline Mucous layer in stomach with mucosal defense mechanisms

22) Describe the disgestion of carbohydrates, proteins and lipids along the length of the GIT.

Digestion can occur at many levels in the body; generally, it refers to the breakdown of

macro-molecules or a matrix of cells, or tissues, into smaller molecules and component parts. This
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particular section will focus on digestion of food in the gastrointestinal tract: the process that is required

to obtain essential nutrients from the food we eat. The gastrointestinal tract (GIT) is a highly specialized

organ system that allows humans to consume food in discrete meals as well as in a very diverse array of

foodstuffs to meet nutrient needs. Figure 1 contains a schematic of the GIT and illustrates the organs of

the body with which food comes into contact during its digestion. These organs include the mouth,

esophagus, stomach, small intestine, and large intestine; in addition, the pancreas and liver secrete into

the intestine. The system is connected to the vascular, lymphatic, and nervous systems; however, the

function of these systems in gastrointestinal physiology is beyond the scope of this article, which focuses

primarily on the process of breaking down macromolecules and the matrix of food.

Mechanical Aspects of Digestion

Food is masticated in the mouth. Chewing breaks food into smaller particles that can mix more readily

with the GIT secretions. In the mouth, saliva lubricates the food bolus so that it passes readily through

the esophagus to the stomach. The sensory aspects of food stimulate the flow of saliva, which not only

lubricates the bolus of food but is protective and contains digestive enzymes. Swallowing is regulated by

sphincter actions to move the bolus of food into the stomach. The motility of the stomach continues theprocess of mixing food with the digestive secretions, now including gastric juice, which contains acid and

some digestive enzymes. The action of the stomach continues to break down food into smaller particles

prior to passage to the intestine. The mixture of food and digestive juices is referred to as digesta, or

chyme. The stomach, which after a meal may contain more than a liter of material, regulates the rate of

digestion by metering chyme into the small intestine over several hours. Several factors can slow the

rate of gastric emptying; for example, solids take longer to empty than liquids, mixtures relatively high in

lipid take longer to empty, and viscous, or thick, mixtures take longer to empty than watery, liquid

contents.

In the upper part of the small intestine, the duodenum, receptors appear to influence the rate of gastric

emptying either through hormonal or neural signals. Peristaltic motor activity in the small intestine

propels chyme along the length of the intestine, and segmentation allows mixing with digestive juices in

the intestine, which include pancreatic enzymes, bile acids, and sloughed intestinal cells. Digestion of

macronutrients, which began in the mouth, continues in the small intestine, where the intestinal surface

provides an immense absorptive surface to allow absorption of digested molecules into circulation.

While the intestine from the outside appears to be a tube, the lining of the inner surface contains tissue

folds and villi that are lined with intestinal cells, each with microvilli, or a brush border, which greatly

amplify the absorptive surface. The intestinal cells can absorb compounds by several cell

membraneediated transport mechanisms and then transform them into compounds, or complexes, that

can enter circulation through the blood, or lymphatic, system.What is not digested and absorbed passes into the large intestine. In this organ, water and electrolytes

are reabsorbed, and the movements of the large intestine allow mixing of the contents with the

microflora of bacteria and other microbes that are naturally present in the large intestine. These

microbes continue the process of digesting the chyme. Eventually the residue enters the rectum and the

anal canal, and stool is formed, which is defecated. Transit time of a non-digestible marker from mouth


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to elimination in the stool varies considerably: normal transit time is typically twenty-four to thirty-six

hours, but can be as long as seventy-two hours in otherwise healthy individuals.

Breakdown of Macromolecules in Foods

Foods are derived from the tissues of plants and animals as well as from various microorganisms. For

absorption of nutrients from the gut to occur, the cellular and molecular structure of these tissues mustbe broken down. The mechanical actions of the GIT help disrupt the matrix of foods, and the

macromolecules, including proteins, carbohydrates and lipids, are digested through the action of

digestive enzymes. This digestion produces smaller, lower molecular weight molecules that can be

transported into the intestinal cells to be processed for transport in blood, or lymph.

Proteins are polymers of amino acids that in their native structure are three-dimensional. Many cooking

or processing methods denature proteins, disrupting their tertiary structure. Denaturation, which makes

the peptide linkages more available to digestive enzymes, is continued in the stomach with exposure to

gastric acid. In addition, digestion of the peptide chain begins in the stomach with the enzyme pepsin.

Once food enters the small intestine, enzymes secreted by the pancreas continue the process of

hydrolyzing the peptide chain either by cleaving amino acids from the C-terminal end, or by hydrolyzing

certain peptide bonds along the protein molecule. The active forms of the pancreatic enzymes include

trypsin, chymotrypsin, elastase, and carboxypeptidase A and B. This process of protein digestion

produces small peptide fragments and free amino acids. The brush border surface of the small intestine

contains peptidases, which continue the digestion of peptides, either to smaller peptide fragments or

free amino acids, and these products are absorbed by the intestinal cells.

Carbohydrates are categorized as digestible or non-digestible. Digestible carbohydrates are the various

sugar-containing molecules that can be digested by amylase or the saccharidases of the small intestine

to sugars that can be absorbed from the intestine. The predominant digestible carbohydrates in foods

are starch, sucrose, lactose (milk sugar), and maltose. Glycogen is a glucose polymer found in someanimal tissue; its structure is similar to some forms of starch. Foods may also contain simple sugars such

as glucose or fructose that do not need to be digested before absorption by the gut. Alpha amylase,

which hydrolyzes the alpha one to four linkages in starch, is secreted in the mouth from salivary glands

and from the pancreas into the small intestine. The action of amylase produces smaller carbohydrate

segments that can be further hydrolyzed to sugars by enzymes at the brush border of the intestinal cells.

This hydrolysis step is closely linked with absorption of sugars into the intestinal cells.

Non-digestible carbohydrates cannot be digested by the enzymes in the small intestine and are the

primary component of dietary fiber. The most abundant polysaccharide in plant tissue is cellulose, which

is a glucose polymer with beta one to four links between the sugars. Amylase, the starch-digesting

enzyme of the small intestine, can only hydrolyze alpha links. The non-digestible carbohydrates also

include hemicelluloses, pectins, gums, oligofructose, and inulin. While non-digestible, they do affect the

digestive process because they provide bulk in the intestinal contents, hold water, can become viscous,

or thick, in the intestinal contents, and delay gastric emptying. In addition, non-starch polysaccharides

are the primary substrate for growth of the microorganisms in the large intestine and contribute to stool

formation and laxation. Products of microbial action include ammonia, gas, and short-chain fatty acids

(SCFA). SCFA are used by cells in the large intestine for energy and some appear in the circulation and


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can be used by other cells in the body for energy as well. Thus, while dietary fiber is classified as non-

digestible carbohydrate, the eventual digestion of these polysaccharides by microbes does provide

energy to the body. Current research is focused on the potential effect of SCFA on the health of the

intestine and their possible role in prevention of gastrointestinal diseases.

For dietary lipids to be digested and absorbed, they must be emulsified in the aqueous environment of

the intestinal contents; thus bile salts are as important as lipolytic enzymes for fat digestion and

absorption. Dietary lipids include fatty acids esterified to a glycerol backbone (mono-, di-or

triglycerides); phospholipids; sterols, which may be esterified; waxes; and the fat-soluble vitamins, A, D,

E, and K. Digestion of triglycerides (TG), phospholipids (PL), and sterols illustrate the key factors in

digestion of lipids. Lipases hydrolyze ester bonds and release fatty acids. In TG and PL, the fatty acids are

esterified to a glycerol backbone, and in sterols, to a sterol nucleus such as cholesterol. Lipases that

digest lipids are found in food, and are secreted in the mouth and stomach and from the pancreas into

the small intestine. Lipases in food are not essential for normal fat digestion; however, lipase associated

with breast milk is especially important for newborn infants. In adults the pancreatic lipase system is the

most important for lipid digestion. This system involves an interaction between lipase, colipase, and bilesalts that leads to rapid hydrolysis of fatty acids from TG. An important step in the process is formation

of micelles, which allows the lipid aggregates to be miscible in the aqueous environment of the

intestine. In mixed micelles, bile salts and PL function as emulsifying agents and are located on the

surface of these spherical particles. Lipophilic compounds such as MG, DG, free sterols, and fatty acids,

as well as fat-soluble vitamins, are in the core of the particle. Micelles can move lipids to the intestinal

cell surface, where the lipids can be transported through the cell membrane and eventually packaged by

the intestinal cells for transport in blood or lymph. Most absorbed lipid is carried in chylomicrons, large

lipoproteins that appear in the blood after a meal and which are cleared rapidly in healthy individuals.

Bile salts are absorbed from the lower part of the small intestine, returned to the liver, and resecreted

into the intestine, a process referred to as enterohepatic circulation. It is important to note that bilesalts are made from cholesterol, and drugs such as cholestyramine or diet components such as fiber that

decrease the amount of bile salt reabsorbed from the intestine help to lower plasma cholesterol

concentrations.

Regulation of Gastrointestinal Function

Regulation of the gastrointestinal response to a meal involves a complex set of hormone and neural

interactions. The complexity of this system derives from the fact that part of the response is directed at

preparing the GIT to digest and absorb the meal that has been consumed in an efficient manner and also

at signaling short-term satiety so that feeding is terminated at an appropriate point. Traditionally,

physiologists have viewed the regulation in three phases: cephalic, gastric, and intestinal. In the cephalicphase, the sight, smell, and taste of foods stimulates the secretion of digestive juices into the mouth,

stomach, and intestine, essentially preparing these organs to digest the foods to be consumed.

Experiments in which animals are sham fed so that food consumed does not actually enter the stomach

or intestine demonstrate that the cephalic phase accounts for a significant portion of the secretion into

the gut. The gastric and intestinal phases occur when food and its components are in direct contact with


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the stomach or intestine, respectively. During these phases, the distension of the organs with food as

well as the specific composition of the food can stimulate a GIT response.

The GIT, the richest endocrine organ in the body, contains a vast array of peptides; however, the exact

physiological function of each of these compounds has not been established. Five peptides, gastrin,

cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), and motilin are established as regulatory

hormones in the GIT. Multiple aspects have been investigated to understand their release and action.

For example, CCK is located in the upper small intestine; protein and fat stimulate its release from the

intestine, while acid inhibits its secretion. Once released, it can inhibit gastric emptying and stimulate

secretion of acid and pancreatic juice and contraction of the gall bladder. In addition, it stimulates

motility and growth in the GIT and regulates food intake and insulin release. Among the other

established gastrointestinal peptides, secretin stimulates secretion of fluid and bicarbonate from the

pancreas, gastrin stimulates secretion in the stomach, GIP inhibits gastric acid secretion, and motilin

stimulates the motility of the upper GIT. In addition to investigating the various factors causing release

of these hormones and the response to them, physiologists are also interested in the interactions

among hormones as well as those with the nervous system, since the response to a meal involvesrelease of many factors.

Obtaining food and digesting it efficiently are paramount to survival. The human GIT system most likely

evolved during the period when the species acquired its food primarily through hunting and gathering.

The over-lapping regulatory systems, combined with an elevated capacity to digest food and absorb

nutrients, insured that humans used food efficiently during periods in which scarcity might occur.

23) Describe the defacation reflex and explainhoe defacation occurs in individuals with spinal cord

injury.

It is a synchronized sequence of events associated with neural influences. There are several

reflexes that are related to the physiology of defecation. The rectum is innervated with nerves that

initiate reflex contractions upon its distention. These contractions altogether constitute the desire to

defecate.

The human rectum has two sphincters: the external anal sphincter, and the internal anal sphincter. In

the internal anal sphincter, the sympathetic nerve supply towards it is excitatory, while the

parasympathetic nerve supply is inhibitory. Thus, this sphincter relaxes when the rectum is being

distended. On the other hand, the external anal sphincter, which is a skeletal muscle, is innervated by a

branch of the pudendal nerve, and this is maintained in a state of contraction. Even a slight increase or

slight distention of the rectum allows it to increase several-fold the force of its contraction. When this

rectal pressure rises to approximately 18 mmHg, the urge to defecate arises. However when this reaches

55 mmHg, this means bad news since both the external and internal anal sphincter will relax and

therefore, there will be a reflex expulsion of fecal matter! This will explain why in animals, expulsion of

rectal contents is not an atypical sight.


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Prior to reaching this seemingly embarrassing pressure point of 55 mmHg, defecation can be made

voluntarily through straining. Defecation is hence a spinal reflex that can be managed through keeping

the external sphincter in its contracted state, or it can be induced through sphincter muscle relaxation

and contracting the muscles of the abdomen.

Ever wondered why at times the urge to defecate happens after a hearty meal? This is because the

stomach, upon distention by food, initiates contraction of the rectum. This is called the gastrocolic

reflex, and there are recent studies that it is a function of gastrin on the colon, and not due to any neural

influence. That is why in children, it is already a given rule that defecation should occur after meals.

In abnormalities involving the colon, these reflexes may be impaired, but not necessarily. It is important

to have quite a little bit of knowledge as to how the mechanism of defecation works, so it would be

easier to understand the abnormal conditions.

Function of the Bowel Following a Spinal Cord Injury

Following a spinal cord injury, damage to the spinal cord may result in the loss of

the ability to control the bowel reflex when the rectum is full, or the reflex toempty the rectum may be lost altogether. The function of the bowel is

maintained by the nerves entering the spinal cord at the sacral levels of S2 - S4.

Due to the voluntary action of the bowel being communicated so low in the

spinal cord, any spinal cord injury will usually have some impact on the

defecation process.

The Reflex Bowel or Upper Motor Neuron Bowel

If the spinal cord injury is above T12, the sensation of a full bowel may no longer

be detectable by the injured person. In such cases, the anal sphincter will remain

closed, however, it will open on a reflex basis when the rectum becomes full.

This type of bowel is referred to as an upper motor neuron bowel reflex. As the

person will not be able to sense when the rectum is full, the reflex to empty the

rectum can happen at any time unless the bowel is managed properly.

The upper motor neurone bowel reflex can be managed to prevent accidental

defecation, by causing the defecation reflex to occur at a socially appropriate

time.

The Flaccid Bowel or Lower Motor Neuron Bowel

If the spinal cord injury is below T12, then there may be damage to the

defecation reflex, and the anal sphincter muscle may relax, staying open. This type of bowel is referred

to as an lower motor neuron bowel or flaccid bowel.

The lower motor neurone bowel reflex can be managed to prevent accidental defecation, by emptying

the bowel more frequently at a socially appropriate time, by bearing down or the manual removal of

stool.


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Both types of bowel, reflex and flaccid, can be managed to avoid the accidental opening of the bowel,

and to avoid constipation and impaction.

24. Discuss the forces involved in glomerular filtration.

The GFR depends on the filtration pressure at the level of the glomerulus, but also on the permeability

of the glomerular membrane and the surface area of the glomerular membrane. Obviously, no matter

how high the filtration pressure, no fluid will filter if the glomerular filtration membrane is not

permeable or has zero surface area.

25. Discuss how GFR is regulated.

-the mechanisms adjust blood flow into and out of the glomerulus and alter the glomerular

capillary surface are available for filtration. It involves renal autoregulation that maintains a constantGFR despite changes in arterial BP with this there is negative feedback control from the JuxtaGlomerular

Apparatus which adjusts local blood pressure and therefore blood volume within each glomerulus. This

is termed tubuloglomerular autoregulation. The smooth muscle in the renal arterioles also makes local

adjustments to blood pressure which adjust for changes in systemic arterial pressure by maintaining the

appropriate pressure gradient between the afferent and efferent arterioles. This is termed myogenic

autoregulation. Second is hormonal regulation by Renin-Angiotensin thus Rennin activates

angiotensinogen to Angiotensin I and it is later further activated by angiotensin-converting enzyme

(ACE) to Angiotensin II. Angiotensin I and Angiotensin II, among other influences, increase systemic

blood pressure and blood volume which will tend to increase GFR. Third is by antagonistic interplay of

Aldosterone and Atrial Natriuretic Peptide (ANP) wherein Aldosterone, from the adrenal cortex,promotes retention of water and sodium ions and excretion of potassium ions, and, therefore, will tend

to increase GFR. Atrial Natriuretic Peptide (ANP) from the atrial walls of the heart promotes retention of

potassium ions and excretion of water and sodium ions, and, therefore, will tend to decrease GFR.

26. What establishes a vertical osmotic gradient in the medullary interstitial fluid? Of what

importance is this gradient?

Interstitial Fluid concentration is 300 mOsm/L at the cortex, and 1200 mOsm/L at the Medulla and the

increasing concentrations are called a Vertical Osmotic Gradient. The active transport pump moves NaClout of the tubule in the ascending Loop of Henle which is impermeable to water and the descending

limb is the only part that does not pump Na+ out, and it is permeable to water, increasing concentration

inside the tubule

The Countercurrent flow of fluid is also necessary for the Vertical Osmotic Gradient


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27. Discuss the function and mechanism of action of ADH.

The primary function of ADH in the body is to regulate extracellular fluid volume by affecting renal

handling of water in which it limits the amount of water being lost in the urine by increasing the amount

of water being reabsorbed into the blood, although it is also a vasoconstrictor and pressor agent (hence,

the name "vasopressin"). ADH acts on renal collecting ducts via V2 receptors to increase waterpermeability (cAMP-dependent mechanism), which leads to decreased urine formation (hence, the

antidiuretic action of "antidiuretic hormone"). This increases blood volume, cardiac output and arterial

pressure.

28. Define plasma clearance. How is this related to the GFR?

Plasma clearance is the measure of the filtration capability of the kidney. it has a direct relationship to

the GFR of the kidney and factors regulated to maintain body fluid balance is plasma osmolality

attributing it to ECF Na concentration and ECF water volume. in order to maintain a normal 300 osmol ofthe ECF of the blood ADH is secreted acting on the collecting tubules of the kidney depending on how

much water is to be secreted to maintain balance.

29. What factors are regulated to maintain the bodys fluid balance?

The factors that need to be regulated are: input and output of water, ADH and Aldosterone.

Input of water is regulated primarily by changes in the volume ingested (controlled by thirst). An

insufficiency of water results in an increased osmolarity in the extracellular fluid. This is sensed by

osmoreceptors, which trigger thirst.

Output of water is regulated primarily by changes in urine volume ( controlled by level of ADH).

The body's homeostatic control mechanisms, which maintain a constant internal environment, ensure

that a balance between fluid gain and fluid loss is maintained. The hormones ADH (also known as

vasopressin) and Aldosterone play a major role in this. If the body is becoming fluid-deficient, there will

be an increase in the secretion of these hormones, causing fluid to be retained by the kidneys and urine

output to be reduced. Conversely, if fluid levels are excessive, secretion of these hormones is

suppressed, resulting in less retention of fluid by the kidneys and a subsequent increase in the volume of

urine produced.

30. How is the plasma concentration of a hormone normally regulated?

The plasma concentration of a hormone is normally regulated by changes in its rate of secretion, and

depends on three factors:

1) hormone's rate of secretion into the blood by the endocrine gland
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> pulsatility - stimulation causes an increase in the frequency of pulses.

2) Hormone's rate of removal from the blood by metabolic inactivation in the liver and/or excretion in

the urine

3) its extent of binding to plasma proteins

31. Discuss the contributions of parathyroid hormone, calcitonin, and vit. D to Ca++ metabolism.

Describe the source and control of each of these hormones

-Parathyroid hormone:

PTH is synthesized and stored in the chief cells of the parathyroid glands. Synthesis is regulated by a feedback mechanism involving the level of blood calcium (and, to a

lesser degree, magnesium).

The primary function of PTH is to control calcium concentration in the extracellular fluid, whichit does by affecting the rate of transfer of calcium into and out of bone, resorption in the

kidneys, and absorption from the GI tract.

The effect on the kidneys is the most rapid, causing reabsorption of calcium and excretion ofphosphorus.

The major initial effect on bone is to mobilize calcium from the bone to the extracellular fluid;later, bone formation may be enhanced. PTH does not directly affect calcium absorption from

the gut. Its effect is mediated indirectly by regulation of synthesis of the active metabolite of

vitamin D.

-Calcitonin:

Is a 32-AA polypeptide hormone secreted by the parafollicular cells of the thyroid gland. The concentration of calcium ion in extracellular fluids is the principal stimulus for the secretion

of calcitonin by parafollicular cells.

The storage of large amounts of preformed hormone in parafollicular cells and rapid release inresponse to a moderate rise in circulating calcium probably reflect the physiologic role of

calcitonin as an emergency hormone to protect against development of hypercalcemia.

Calcitonin exerts its effects by interacting with target cells, primarily in the bone and kidney. The actions of PTH and calcitonin are antagonistic on bone resorption but synergistic on

decreasing the renal tubular reabsorption of phosphorus.


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The hypocalcemic effects of calcitonin are primarily the result of decreased entry of calciumfrom the bones into plasma, resulting from a temporary inhibition of PTH-stimulated bone

resorption.

The hypophosphatemia develops from a direct action of calcitonin, which increases the rate ofmovement of phosphorus out of plasma into soft tissue and bone and inhibits the boneresorption stimulated by PTH and other factors.

-Vitamin D:

Major hormone involved in the regulation of Ca++ metabolism next to PTH. Must be metabolically activated first before it can function physiologically. The biologic actions of vit. D depends on hydroxylation in the liver and kidney to form the

biologically active form (1, 25-dihydroxyvitamin D [calcitriol]).

This conversion in the kidneys is the rate-limiting step in vit. D metabolism and is partlyresponsible for the delay between vit. D administration and expression of its biologic effects.

PTH = active Vit. D circulating phosphorus conc. =active Vit. D

32. What are the biochemical classes of hormones? How do these classes differ from each other in

terms of synthesis, storage, circulation, and mechanism of action?

Hormones are classified into three biochemical categories: Steroids Proteins/peptides Amines


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33. Explain how glucose regulates the secretion of insulin in beta cells

Transport of glucose into beta cells through GLUT-2 transporter proteinsMetabolism ofglucose inside the beta cellsProduction of ATP (or NADP+) Then, this closes (the ATP

molecule) the K+ channels Depolarization Voltage-gated Ca+ channels open

intracellular Ca+ Exocytosis of insulin from secretory granules

The beta cell's primary function is to correlate release of insulin with changes in blood glucose

concentration using a glucose transport protein (GLUT2) and a kinase (glucokinase) both of which


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have low affinities for glucose. GLUT2 is quite active, but the Km for glucose is around 5

mmol/l. Therefore, transport of glucose into the beta cell is rapid, but only when the blood glucose

concentration exceeds post-meal levels.

The next component of the glucose sensor is glucokinase, the enzyme that initiates

glycolysis. Unlike hexokinase, glucokinase has a low affinity for its substrate. Glucokinase activity

increases and decreases parallel to changes in blood glucose levels within the physiological range.

Glucokinase activity is, therefore, most sensitive to changes in blood glucose concentration within

the physiological range (approximately 4-6 mmol/l).

Consequently, both uptake of glucose by the beta cell and initiation of glycolysis closely follow blood

glucose levels. We have a system that responds to increases in blood glucose with a rapid uptake

and metabolism of glucose, but which is rather sluggish at the glucose levels found between

meals. The "glucose sensor pair" GLUT2-GK is also found in the liver and hypothalamus and seems

to be the universal glucose sensor.

The resting membrane potential of about -60 mV found in beta cells arises from loss of K+ ions to the

extracellular space. The distinguishing characteristic of this ion channel in beta cells is that it isbound to a regulatory protein, known as SUR1. This name comes from the fact that this protein is

the receptor for sulfonylurea compounds(with hypoglycemic effect).

The Kir6.2-SUR1 complex is now known as the KATPchannel. The complete channel consists of a core

of four Kir 6.2 subunits surrounded by four SUR1 subunits. The SUR1 complex acts as a regulator of

the K+ channel, binding ATP as well as sulfonylurea compounds. Both ATP and tolbutamide have

inhibitory actions on the KATP channel and therefore inhibit K+ efflux. This leads to depolarization of

the beta cell, Ca++ influx and insulin secretion. Another agent, diazoxide, stimulates the KATP channel

and promotes K+ efflux, membrane polarization and inhibition of insulin secretion.

*** The classical viewpoint has been that the pancreatic beta cell obtains its energy supply throughaerobic glycolysis, using glucose as substrate. However, resting beta cell oxidative phosphorylation may

be dependent upon oxidation of fatty acids (discussed later). The rate of fatty acid beta oxidation may

limit oxidative phosphorylation. The ATP/ADP ratio is relatively low in beta cells exposed to fasting

blood glucose levels. The accelerated glucose uptake found at glucose levels over 5 mmoles/l augments

ATP synthesis. In other words, ATP synthesis is dependent upon the rates of glucose uptake and aerobic

glycolysis. Variations in ATP levels occur parallel to changes in blood glucose concentration. ATP acts as

a second messenger in these cells, informing the KATP channel of variations in blood glucose

levels. Stated simply: more glucose, more ATP, increased INHIBITION of K+ transport, depolarization of

the beta cell and then, release of insulin.

Incidentally, it has been suggested that both PIP2 and ADP levels may be just as important as ATP inregulation of KATP and membrane polarization. *

The final element in the signal system for insulin secretion is the voltage-dependent Ca++

(VDCC)

channel. This opens when the membrane voltage falls to less than -40 mvolts. The Ca++

that then

enters the cell is directly involved in the exocytotic process that releases insulin form the "rapidly

released pool" of insulin-containing granules.


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*****SHORTER

VERSION

GLUT2 and

glucokinase are

activated when blood

glucose increase to

about 5.5

mmol/l. Aerobic

glycolysis will drive the

ATP/ADP ratio

upwards. The ATP

produced inhibits the

KATP channel, thus

reducing the flow of

potassium ions from

the beta cell. As a

result, the cellbecomes increasingly

depolarized. Slow

depolarization waves

are initiated as the

membrane potential

falls. Action

potentials occur at the tops of these waves. Insulin secretion is pulsatile, the hormone being

secreted in bursts that occur simultaneously with the action potentials. Calcium causes exocytosis

from the "rapidly released pool" and migration of insulin-containing granules from the "reserve pool"

to the cell membrane where they are "docked" and energized.

34. Enumerate the effects of insulin in the liver, muscle, and fat cells

LIVER:

Stimulates GLYCOGENESIS Inhibits GLUCONEOGENESIS Promotes LIPOGENESIS Stimulates PROTEIN SYNTHESIS

MUSCLE:

Promotes UPTAKE OF GLUCOSE via GLUT4 Promotes GLYCOGEN SYNTHESIS


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Promotes GLYCOLYSIS Promotes PROTEIN SYNTHESIS

FAT CELLS:

Promotes UPTAKE OF GLUCOSE via GLUT4 Promotes GLYCOLYSIS Promotes SYNTHESIS OF TGs Inhibits HORMONE-SENSITIVE TG LIPASE Promotes SYNTHESIS OF LIPOPr LIPASE

35. Describe the regulation of thyroid activity by the hypothalamus and anterior pituitary.

The secretion of hormones from the thyroid gland is regulated by negative feedback in the

hypothalamicpituitarythyroid axis. The hypothalamus secretes TRH, which stimulates the release of

TSH from the adenohypophysis of the pituitary. Thyroid-stimulating hormone then stimulates the

release of T3 and T4 from the thyroid. In this hormone axis, negative-feedback inhibition is exerted

primarily at the level of the pituitary. As the intracellular concentration of T3 in the thyrotroph cells of

the pituitary increases, then the responsiveness of these TSH-producing cells to TRH decreases. The

mechanism of this decreased responsiveness involves down regulation of TRH receptors. This results in a

decrease in the secretion of TSH and, consequently, a decrease in the secretion of T3 and T4. The excess

of intracellular T3 that elicits the negative feedback control of secretion comes from two sources: 80%

from the deiododination of serum T4 within the thyrotroph cells and 20% from serum T3.

36. Explain how thyroid hormones affect cell activity following interaction with its nuclear receptor.

DEIODINATION OF T4T3 IN PERIPHERAL CELLS THYROID HORMONE-RECEPTOR COMPLEX EFFECTS ON METABOLISM IN DIFFERENT CELLS


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Receptors for thyroid hormones are intracellular DNA-binding proteins that function as

hormone-responsive transcription factors, very similar conceptually to the receptors for steroid

hormones.

Thyroid hormones enter cells through membrane transporter proteins. A number of plasma

membrane transporters have been identified, some of which require ATP hydrolysis; the relative

importance of different carrier systems is not yet clear and may differ among tissues. Once inside the

nucleus, the hormone binds its receptor, and the hormone-receptor complex interacts with specific

sequences of DNA in the promoters of responsive genes. The effect of the hormone-receptor complex

binding to DNA is to modulate gene expression, either by stimulating or inhibiting transcription of

specific genes.

37. Describe the hormonal, ovarian, and uterine changes during the entire menstrual cycle.

Estrogen secondary sexual characteristics

- estradiol - most important; dominant

- stimulate bone and muscle growth

- maintain secondary sex characteristics

- affecting CNS activity

- maintain functional accessory reproductive glands and organs

- initiate growth and repair of endometrium


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Effects of Estrogen:

Uterus & external genitalia- increase in size- fat deposition in mons pubis- epithelial change from cuboidal to stratified - more resistant to trauma & infection- proliferation of endometrium- development of endometrial glands Fallopian tubes- increased glandular tissues- increased number and activity of ciliated epithelial cells Breasts- development of stromal tissue- growth of ductile system- deposition of fat Protein deposition- slight increase in total body protein Bones- increase osteoblastic activity- early uniting of epiphysis of long bones- menopause - no estrogen - decrease osteoblastic activity osteoporosis Fat deposition- increased metabolic rate- deposition in thighs and buttocks Hair Distribution- fairly distributed Electrolyte imbalance- water and Na retention - chemical similarity to adrenocortical hormone; significant in pregnancy

Progestin - progesterone - for pregnancy and lactation

- non-pregnant: secreted by corpus luteum

- pregnancy: placenta, after 4 months

Follicular phase

This phase is also called the proliferative phase because a hormone causes the lining of

the uterus to grow, or proliferate, during this time.

Through the influence of a rise in follicle stimulating hormone (FSH) during the first days

of the cycle, a few ovarian follicles are stimulated.[20] These follicles, which were present at

birth[20] and have been developing for the better part of a year in a process known as

folliculogenesis, compete with each other for dominance. Under the influence of several

hormones, all but one of these follicles will stop growing, while one dominant follicle in the

ovary will continue to maturity. The follicle that reaches maturity is called a tertiary, or Graafian,

follicle, and it forms the ovum.

As they mature, the follicles secrete increasing amounts of estradiol, an estrogen. The

estrogens initiate the formation of a new layer of endometrium in the uterus, histologically


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identified as the proliferative endometrium. The estrogen also stimulates crypts in the cervix to

produce fertile cervical mucus, which may be noticed by women practicing fertility awareness.

Ovulation

During the follicular phase, estradiol suppresses production of luteinizing hormone (LH)

from the anterior pituitary gland. When the egg has nearly matured, levels of estradiol reach a

threshold above which this effect is reversed and estrogen actually stimulates the production of

a large amount LH. This process, known as the LH surge, starts around day 12 of the average

cycle and may last 48 hours.

The exact mechanism of these opposite responses of LH levels to estradiol is not well

understood. In animals, a GnRH surge has been shown to precede the LH surge, suggesting that

estrogen's main effect is on the hypothalamus, which controls GnRH secretion. This may be

enabled by the presence of two different estrogen receptors in the hypothalamus: estrogen

receptor alpha, which is responsible for the negative feedback estradiol-LH loop, and estrogen

receptor beta, which is responsible for the positive estradiol-LH relationship. However in

humans it has been shown that high levels of estradiol can provoke abrupt increases in LH, even

when GnRH levels and pulse frequencies are held constant, suggesting that estrogen acts

directly on the pituitary to provoke the LH surge.

The release of LH matures the egg and weakens the wall of the follicle in the ovary,

causing the fully developed follicle to release its secondary oocyte. The secondary oocyte

promptly matures into an ootid and then becomes a mature ovum. The mature ovum has a

diameter of about 0.2 mm.

After being released from the ovary and into the peritoneal space, the egg is swept into

the fallopian tube by the fimbria, which is a fringe of tissue at the end of each fallopian tube.

After about a day, an unfertilized egg will disintegrate or dissolve in the fallopian tube.

Fertilization by a spermatozoon, when it occurs, usually takes place in the ampulla, the widest

section of the fallopian tubes. A fertilized egg immediately begins the process of embryogenesis,

or development. The developing embryo takes about three days to reach the uterus and

another three days to implant into the endometrium. It has usually reached the blastocyst stage

at the time of implantation.

In some women, ovulation features a characteristic pain called mittelschmerz (German

term meaning middle pain). The sudden change in hormones at the time of ovulation sometimes

also causes light mid-cycle blood flow.

Luteal phase

The luteal phase is also called the secretory phase. An important role is played by the

corpus luteum, the solid body formed in an ovary after the egg has been released from the

ovary into the fallopian tube. This body continues to grow for some time after ovulation and

produces significant amounts of hormones, particularly progesterone. Progesterone plays a vital

role in making the endometrium receptive to implantation of the blastocyst and supportive of

the early pregnancy; it also has the side effect of raising the woman's basal body temperature.


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After ovulation, the pituitary hormones FSH and LH cause the remaining parts of the dominant

follicle to transform into the corpus luteum, which produces progesterone. The increased

progesterone in the adrenals starts to induce the production of estrogen. The hormones

produced by the corpus luteum also suppress production of the FSH and LH that the corpus

luteum needs to maintain itself.

Consequently, the level of FSH and LH fall quickly over time, and the corpus luteum

subsequently atrophies. Falling levels of progesterone trigger menstruation and the beginning of

the next cycle. From the time of ovulation until progesterone withdrawal has caused

menstruation to begin, the process typically takes about two weeks, with 14 days considered

normal. For an individual woman, the follicular phase often varies in length from cycle to cycle;

by contrast, the length of her luteal phase will be fairly consistent from cycle to cycle.

The loss of the corpus luteum can be prevented by fertilization of the egg; the resulting

embryo produces human chorionic gonadotropin (hCG), which is very similar to LH and which

can preserve the corpus luteum. Because the hormone is unique to the embryo, most pregnancy

tests look for the presence of hCG.

38. Describe the effects of testosterone and dihydrotestosterone on the male body during puberty.

Testosterone

- produced by Leydig cells in the interstitium of the testis

- for growth and division of the testicular germinal cells (first stage in forming sperm)

- spermatogenesis

- Decrease in GnRH Secretion (negative regulation on the Hypothalamus)

- Inhibits LH Secretion (negative regulation on the Pituitary Gland)

- Development of Male Accessory Reproductive Organs

- Responsible for Male Secondary Sex Characteristics (Distribution of Body Hair, Baldness

Voice, Skin, Acne)

- Stimulates Protein Anabolism, Bone Growth and Cessation of Bone Growth

- Maintains Sex Drive and may enhance aggressive behavior

- increases the RBCs

Dihydrotestosterone

- 5-A-Reductase converts Testosterone to Dihydrotestosterone (DHT)

- DHT has approximately three times greater affinity for androgen receptors than testosterone

and has 15-30 times greater affinity than adrenal androgens


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- During embryogenesis: formation of the male external genitalia, while in the adult DHT acts as

the primary androgen in the prostate and in hair follicles

39. Discuss the ionic basis of resting membrane potentials and the action potentials in nerve and

skeletal muscle tissues.

Phospholipid bilayer prevents non-soluble ions from passing through the lipid component,allowing separation of charges

Resting ion channels (leaky channels or non-gated) allows diffusible ions to pass (more leaky Kion channels than Na ion channels)

Energy-dependent Na-K Pump (Na-K/ATPase System) contributes to long term Passive fluxes of Ion across the cell membrane decrease concentration of electrical gradients

(K efflux) through leaky K channels which determines RMP (resting membrane potential).

40. Discuss the different stages of synaptic transmission.

Stages:

Synthesis and storage of neurotransmittersThe first step in synaptic transmission is the synthesis and storage of neurotransmitters.

There are two broad categories of neurotransmitters. Small-molecule neurotransmitters are

synthesized locally within the axon terminal. Some of the precursors necessary for the synthesis

of these molecules are taken up by selective transporters on the membrane of the terminal.

Others are byproducts of cellular processes that take place within the neuron itself and are thus

readily available. The enzymes necessary to catalyze an interaction among these precursors are

usually produced in the cell body and transported to the terminal by slow axonal transport.

Acetylcholine (ACh), is an example of an excitatory small-molecule neurotransmitter.

This important, well-studied neurotransmitter, made up of choline and acetate, is found atvarious locations throughout the central and peripheral nervous systems and at all

neuromuscular junctions. The synthesis of ACh requires the enzyme choline actyltransferase

and, like all small-molecule neurotransmitters, takes place within the nerve terminal.

Neuropeptides are the seco

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