Professional Documents
Culture Documents
Human Physiology Lectures
Human Physiology Lectures
•
• Bilayer forms a barrier to passage of molecules in an out of cell
• Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
• Cholesterol (another lipid) stabilizes cell membranes
• In the drawing note that the hydrophobic tails of the phospholipids (fatty acids) are
together in the center of the bilayer. This keeps them out of the water
• Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
• Hydrophobic = doesn't like water = likes lipids
1
• If the concentration of molecules is different in 2 regions diffusion will cause molecules
to move from a region of high concentration to one of low concentration
o Concentration gradient = (concentration at point 2 - concentration at point 1)
• The higher the concentration gradient the more rapid the net diffusion
o Rate of diffusion = diffusion constant X concentration gradient
• Diffusion tries to even out the concentrations so they are equal everywhere
• Simple diffusion across a membrane is called permeability
• Diffusion is most efficient over short distances (about the diameters of cells)
• Hydrophobic chemicals cross membranes faster than those that like water
• Simple diffusion through a membrane = permeability
• Many biological chemicals are deliberately made hydrophobic to increase their rate of
penetration into cells. Examples: many drugs, pesticides such as DDT
• Energy from ATP is not required for this type of penetration
• Hydrophobicity is measured by oil/water partition
• Osmosis = movement of water from low osmotic pressure (dilute solution) to high
osmotic pressure (concentrated solution)
• Except for blood flow almost all water movement in body is osmosis
2
• It is useful to think of a dilute solution as having a high water concentration and a
concentrated solution as having a lower water concentration. Then the water flow goes
from high water to low water concentration.
o In the picture the purple dots represent the solute (the higher the solute
concentration the lower the water concentration
• Osmosis is passive: doesn't require ATP energy
• Except for the pumping of the blood, all water movements in the body are by osmosis
• Osmotic flow through most biological membranes is not by simple diffusion- it is by bulk
flow and is similar to the flow caused by a pressure gradient
• The kidney is an osmotic machine: it adjusts body water volume by osmosis
• Medical problems involving osmosis: pulmonary edema, childhood diarrhea, cholera,
inflammation of tissues
• Cholera is caused by osmotic imbalances, but can be treated using osmotic techniques.
Click to get information on oral rehydration therapy for cholera and other diseases
involving diarrhea.
• There is so much water that osmosis often produces significant volume changes, causing
swelling or shrinking
• If the external solution balances the osmotic pressure of the cytoplasm it is said to be
isotonic.
• If the external solution is more dilute than the cytoplasm it is hypotonic and if the
external solution is more concentrated it is hypertonic.
• Cell B is in an isotonic solution. What kind of solutions are cells A, C, and D in? Check
your answer.
3
• Protein transport molecules are used to carry many substances across membranes
In the drawing an extracellular molecule binds to the transport protein; the transport
protein then rotates and releases the molecule inside the cell
o Examples:
Glucose transporters- 5 different GLUT proteins and 2 types that
cotransport Na and glucose (these are used for secondary active transport)
Water channels- 8 different types of aquaporins
• Properties of facilitated diffusion
o Facilitated diffusion cannot cause net transport of molecules from a low to a high
concentration- this would require input of energy
o ATP energy not required
o Transport rate reaches a maximum when all of the protein transporters are being
used (saturation)
o Very specific: allows cell to select substances taken up
o Sensitive to inhibitors that react with protein side chains
• Pumps are proteins that use energy to carry substances across the cell membrane
o Can transport substances from a low concentration to a high concentration
("uphill" transport)
o ATP energy required
o Examples: the Na/K pump, the Ca pump, etc..
o Transport rate reaches a maximum when all of the protein transporters are being
used (saturation)
o Very specific: allows cell to select substances taken up
o Sensitive to inhibitors that react with protein side chains
• Of ancient origin: found in all organisms
• Extremely important in physiology: about a third of your basal metabolism is used in
active transport of various substances
4
o Na gradient is produced by the Na pump (active transport)
o The Na concentration gradient is used to produce secondary transport of sugars
and amino acids (facilitated diffusion)
Some sugar and amino acid transporters must bind Na as well as the sugar
or amino acid (coupled transport)
Both Na and the organic molecule must be present at the same time and on
the same side of the membrane
Since there is more Na outside the cell, sugars and amino acids get
transported mainly from the outside to the inside
The sugar and amino acid transporters do not use ATP directly, but ATP is
required to set up the Na gradient
o Examples:
Glucose transport across the wall of the gut.
Cotransport and the treatment of cholera.
• If a molecule is moved across the cell membrane by a protein transporter or pump adding
more transporters or pumps will increase the transport rate; removing transporters or
pumps will decrease the transport rate
• Often transport proteins are stored in vesicles until needed
o The transporters are down-regulated, back into vesicles, when they are not needed
• In other cases new transporters must be synthesized when needed
• The body uses hormones to regulate membrane transport in this way
• Examples:
5
Aldosterone causes cells in the distal
tubules and collecting duct of the
kidney to make more Na pump
Aldosterone Na Pump
molecules. The final result is that the
body retains more Na and secretes
more K into the urine.
Note that most of the special properties of facilitated and active transport (those checked "yes")
are due to the protein nature of the transport molecules. To get active transport energy must be
added to the system.
More Information:
Gwen Childs of the University of Texas has a well-designed cell membrane website. The
graphics are excellent but take a little time to load.
Joe Patlak of the University of Vermont and Chris Watters of Middlebury College have produced
nice animations of simple diffusion and osmosis.
For an advanced look at membrane proteins with nice graphics click on this site at the Martin
Luther Universitat, Halle-WittenbergLecture 10: Membrane Electricity
6
• Voltages are caused by separation of charges
• Consider a membrane with equal numbers of cations and anions on both sides. Since both
sides have equal numbers of charges the membrane potential will be zero:
• Now suppose you move a few cations from inside a cell across the membrane to the
outside:
• The inside is left with a negative charge and the outside acquires a positive charge
o A voltage now exists across the membrane, with the inside negative
o Most cells have transmembrane voltages (membrane potentials) of this sort
o This is called a negative membrane potential
• The magnitudes of membrane potentials are usually in the range of 10 to 100 millivolts (1
mV = 0.001 volts). For comparison a flashlight battery has 1.5 volts or 1500 millivolts
(mV)
• Membrane potentials will occur across cell membranes if
o 1) there is a concentration gradient of an ion
o 2) there is an open channel in the membrane so the ion can move from one side to
the other
7
o This is a form of active transport- can pump ions "uphill", from a low to a high
concentration
o This produces concentration gradients of Na & K across the membrane
o Typical concentration gradients:
In mM/L Out mM/L Gradient orientation
Na 10 150 High outside
K 140 5 High inside
o The ion gradients represent stored electrical energy (batteries) that can be tapped
to do useful work
o The Na pump is of ancient origin, probably originally designed to protect cell
from osmotic swelling
o Inhibited by the arrow poisons ouabain and digitalis
• Notes:
o Concentrations are in millimoles/liter (.15 moles/liter = 150 millimoles/liter)
o Membrane potential is in millivolts (.07 volts = 70 millivolts)
o Membrane potentials are proportional to the ion ratios on the 2 sides of the
membrane. Click to see how to calculate the membrane potential using the Nernst
or Goldman equation.
• All cells have Na pumps in their membranes, but some cells have more than others
• Over-all Na pump activity may account for a third of your resting energy expenditure!
• In the kidney the Na pump activity is very high because it is used to regulate body salt
and water concentrations
o Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of
the oxygen supply
8
• Pump activity is also high in the brain because Na and K gradients are essential for
nerves
o The brain is another high energy organ; it is 2% of body weight, but uses 18% of
the oxygen supply
In the Resting State Potassium Controls the Membrane Potential of Most Cells
During an Action Potential Na Channels Open, and Na Controls the Membrane Potential
• Whichever ion has the most open channels controls the membrane potential
• Excitable cells have Na channels that open when stimulated
• When large numbers of these channels open Na controls the membrane potential
• How will the membrane potential change when Na channels open? Click to check your
answer.
• Hydrogen ion is extremely reactive and effects many molecules which regulate
physiological processes
• Blood pH is set at a slightly alkaline level of 7.4 (pH 7.0 is neutral)
• A change of pH of 0.2 units in either direction is considered serious
• Blood pHs below 6.9 or above7.9 are usually fatal if they last for more than a short time
• Buffers are mixtures of two chemicals, weak acids, that resist pH changes:
o if the pH is too low one chemical will bind some of the hydrogen ions and raise
the pH:
H +A -> HA
Example: A = bicarbonate
o if the pH is too high the other chemical will donate some hydrogen ions to lower
the pH
HA -> H + A
Example: HA = carbonic acid
9
The Chief Blood Buffer is a Mixture of Bicarbonate and Carbon Dioxide
• All body fluids, inside or outside cells have buffers which defend the body against pH
changes
• The most important buffer in extracellular fluids, including blood, is a mixture of carbon
dioxide (CO2) and bicarbonate anion (HCO3)
• CO2 acts as an acid (it forms carbonic acid when it dissolves in water), donating
hydrogen ions when they are needed
• HCO3 is a base, soaking up hydrogen ions when there are too many of them
• The HCO3/CO2 buffer system is extremely important because it can be rapidly
readjusted in alkalosis and acidosis
• There are also other buffers in blood, such as proteins and phosphate
• The ability to resist pH change is given by the buffer capacity, which is a function of the
concentration and dissociation constant (pK) of the weak acid
• If there is more than one buffer in the solution, the buffer capacities add up
• Blood pH is determined by a balance between bicarbonate and CO2 ad shown by these
diagrams:
• The balance will swing toward a low pH, producing acidosis, if CO2 is raised or HCO3
lowered
• CO2 can be raised by hypoventilation (pneumonia, emphysema)
• Metabolic conditions such as ketoacidosis caused by excess fat metabolism (diabetes
mellitus) will lower bicarbonate
10
• Compensation for acidosis (rebalances the pH to 7.4):
o Add HCO3
o Remove CO2: occurs first because lungs work faster than kidneys
• The balance will swing the other way, producing alkalosis, if CO2 is lowered or HCO3
raised
• CO2 can be lowered by hyperventilation
• Vomiting removes stomach acid and raises bicarbonate
• Alkalosis is less common than acidosis
11
• Almost all of the CO2 is removed, as a gas, from the lungs
• If blood pH is low respiration is stimulated so that more CO2 is removed, raising the pH
to the normal level
• Bicarbonate is adjusted in the kidney
o Most filtered bicarbonate is reabsorbed in the proximal tubule
• The kidneys also dispose of non-volatile acids produced in metabolism
• Additional processes are used by the kidney to regulate pH:
o Secretion of H ions
Occurs in the proximal tubule and distal tubules
Secretion into blood lowers the pH
Secretion into the tubule raises the pH
o Production of new bicarbonate in distal tubule:
The distal tubule has fine control over bicarbonate
Secreted into the blood raises the pH
Secretion into tubule lowers the pH indirectly
o Production of ammonia (NH3) in proximal tubule cells during acidosis
Helps to remove excess H by forming ammonium ion (NH4+) in the
tubule
More Information
Acid/base shifts in the blood are a major concern of medicine and there are several websites
discussing such problems in detail:
• Both bone and teeth contain the mineral hydroxyapatite (Ca phosphate with some OH
groups) associated with a cartilage (protein) matrix
• In addition to supporting the body the skeleton is a storage depot for Ca
o Ca can be added to or removed from the skeleton to keep the blood level at the
correct value
• Teeth & bone structure:
Organic &
Mineral Notes:
water
12
Innermost layer of teeth.
Pulp 0% 100% Contains connective tissue,
blood vessels, nerves.
Main tooth structure.
Middle layer. Similar to
Dentin 70% 30% bone in structure. Secreted
by odontoblasts lining pulp
cavity.
Hard outer surface of tooth.
Enamel 97% 3% Secreted by ameloblast
cells.
Lines the root of the tooth
and helps hold the it in the
Cementum 61% 39%
socket. Secreted by the
peridontal membrane.
Secreted by osteoblasts and
broken down by osteoclasts.
Bone 65% 35%
These processes occur
continuously (remodeling).
• Compact bone in the shafts of long bones is organized into Haversian systems
o Cylindrical rings of bone- have cavities with osteocyte bone cells
o Central canal with blood vessels, nerves
• Long bones (femur, humerus, radius, ulna, tibia, fibula, etc.) have a shaft and heads
(epiphyses) at each end
• Epiphyseal plates (soft, no Ca) allow bone to grow in length- sealed at puberty
• No growth in length after puberty
13
• If bone is subjected to weight bearing stress it will remodel into reinforced stronger bone
• If bone is not weight bearing it will decalcify and become weaker (disuse atrophy- seen
in astronauts and patients with long bed rests
• About half the serum Ca is ionized (divalent cation)- the rest is bound to proteins
• Secretion of hormones into blood and release of transmitters in synapses requires proper
level of ionized serum Ca
• Contraction of skeletal and heart muscle requires flow of ionized Ca into cytoplasm
• Ca is also one of the hormone "second messengers"
Production Function
Made by parathyroid Raises blood Ca.
glands (4 bodies Reduces kidney
imbedded in the excretion, raises
Parathyroid hormone
thyroid gland). A intestinal absorption
peptide with 84 amino and releases bone Ca
acids. Half life 10 min.into blood.
Made in steps by 3 Raises blood Ca.
Calcitrol (active
different organs: skin, Promotes intestinal
vitamin D)
liver, kidney absorption of Ca.
Made by C cells of
thyroid gland. A 32 Reduces blood Ca.
Calcitonin amino acid peptide. Inhibits bone resorption
Half life less than 10 by reducing osteoclasts.
min.
•
14
• Other hormones affecting Ca:
o Estrogens: promote bone growth. When estrogens are reduced at menopause,
osteoporosis is accelerated.
o Testosterone: stimulates bone and cartilage growth
o Growth hormone: promotes bone and cartilage growth and increases intestinal
absorption of Ca
• The are 4 parathyroids glands, located on the dorsal side of the thyroid
• Parathyroid hormone (PTH) is a peptide
o Made as a "prohormone" of 110 amino acids
o Later converted to the active hormone of 84 amino acids (in the endoplasmic
reticulum & Golgi apparatus)
• Parathyroid hormone raises blood Ca by acting on 3 organs:
o Bone: main effect- stimulates osteoclasts -> bone breaks down -> Ca released
o Intestines: increases uptake of Ca from intestine
o Kidney: stimulates reabsorption of Ca from the Ca in kidney tubules
15
•
• Vitamin D is really a hormone- we put it in the diet and call it a vitamin because many
people do not make enough in their body
o Melanin pigment in skin absorbs UV light; melanin pigment in different ethnic
groups may be an adaptation to allow the right amount of UV to enter the skin
o Deficiency of vitamin D may occur in winter due to less exposure to sunlight
• Deficiency of vitamin D causes rickets in children and osteomalacia in adults
o In children with rickets leg bones are bowed because they are soft
o Rickets is rare in this country because milk is supplemented with vitamin D
• The vitamin D steroids are hydrophobic and are carried in the blood bound to special
carrier proteins
16
• As we get older our bones decalcify and become more susceptible to fracture ->
osteoporosis
• Probably due to reduced levels of sex hormones
• Osteoporosis much more common in women- they live longer (more time to decalcify)
• About 1.5 million fractures due to osteoporosis in this country every year
• By the age of 80 a large percentage (about 30%)of American women have hip fractures
More Information
Although the Kidneys are Tiny Organs They Receive 25% of the Cardiac Output
• The 2 kidneys are only 0.4% of the body weight but receive about 25% of the blood flow
17
o Blood flow rate per kilogram of tissue is almost 8 times higher in the kidneys than
through muscles doing heavy exercise!
Kidney: 4 liters/kg-min
Exercising muscle: 0.55 liters/kg-min
• Extremely important function: to regulate the composition and volume of body fluids
• Blood flows in and out of kidney leaving behind the 1% which becomes urine
• Urine flows through ureters to bladder and then through urethra to outside world
• The bladder is under both voluntary and autonomic control
Kidneys Filter About 180 Liters of Plasma Every Day, But Make Only 2 Liters of Urine
• The kidneys filter approximately 180 liters of plasma/day (each of the 3 liters of plasma
gets filtered about 60 times)
• To replace this much water you would have to drink a 12 ounce soft drink every 3
minutes of the day
• Fortunately 99% of the filtrate gets reabsorbed, leaving 1.5-2 liters of urine per day
• It is remarkable that the kidney filter can be used continuously for 70 years or more
without becoming clogged
The Basic Processes of the Kidney are Filtration, Reabsorption and Secretion
• Filtration:
o About 20% of the plasma that passes through the kidney gets filtered into the
nephron
o Filtration is takes place in the glomerulus
18
o Driven by the hydrostatic pressure of the blood (osmosis opposes filtration, but
the hydrostatic pressure is larger)
o Water and small molecules are filtered; blood cells and large molecules (most
proteins) do not pass through the filter
Substance % Reabsorbed
Water 99.4%
Na 99.4%
K 93.3%
HCO3 100%
Glucose 100%
Urea 53%
Inulin 0%
19
quickly remove many toxic substances from the blood (they are usually not
reabsorbed)
• Net Process:
o Amt in Urine = Amt Filtered - Amt Reabsorbed + Amt Secreted
• The rate at which the kidney filters blood plasma is called the glomerular filtration rate
(GFR)
• It is relatively easy to measure the GFR and it is a good way of assessing kidney function
• Consider a substance, A, which is only filtered by the kidney; it is neither reabsorbed nor
secreteted
o Since no A is reabsorbed from or secreted into the tubule, the amount filtered into
the tubule at the glomerulus must equal the amount appearing in the urine
P X GFR = U X V
P = plasma concentration of A, in mg/mL
GFR = glomerular filtration rate of plasma, in mL/min
U = urine concentration of A, in mg/mL
V = rate of urine production in, in mL/min
o Solving the equation for GFR will give:
GFR = (U X V)/P
• Two substances are used to measure GFR:
o Inulin: a polysaccharide which is not metabolized by the body. Inulin is not found
in the body and must be injected. This substance gives the most accurate results
and is used for research purposes.
o Creatinine: a breakdown product from creatine phosphate, which is naturally
found in the blood. Not quite as accurate as inulin (about 10% is reabsorbed), but
often used in medicine, since no injection is required.
o GFR measurements are very easy to do and give an assessment of kidney
function. It is important to do these measurements in older patients and in others
who may have kidney impairment
• For substances which are reabsorbed and/or secreted the formula is slightly different:
o PXC=UXV
o C = clearance rate of the substance (takes into account secretion and reabsorption)
o C = (U X V)/P
• Clearance measurements tell you how the kidney handles the substance:
o Filtered + reabsorbed: C will be less than the GFR
20
o Filtered only: C = GFR (about 120 mL/min)
o Filtered + secreted: C will be higher than the GFR
• Most of the solutes filtered into the tubule are reabsorbed because they are too valuable to
throw away
• In many cases reabsorption is by active transport, requiring ATP
o Because of the active transport the kidney is an energy intensive organ
• Example of active transport: Na, K pump:
o Most of the filtered Na is reabsorbed by the Na pump in the proximal tubule
(~65%)
o Na pumping in the ascending loop of Henle sets of osmotic gradients that are used
to regulate water (~25%)
o Fine tuning of Na is done by Na pumps in the distal tubule and collecting duct,
which are controlled by the hormone, aldosterone
• Some reabsorption is by secondary active transport- the flows are indirectly coupled to
the active transport of another substance (such as Na)
• Example of secondary active transport: Glucose reabsorption
o The proximal tubule has a mechanism for cotransport of Na & glucose
21
o The kidney can reabsorb glucose at a tubular maximum rate of 320 mg/min
o If plasma glucose is normal (about 100 mg/deciliter) 125 mg/min of glucose is
filtered into the tubules
o At this filtration rate the kidney can reabsorb 100% of the glucose in the proximal
tubule
o If the plasma concentration gets high enough (about 300 mg/deciliter) the filtered
glucose rate will exceed the tubular maximum for glucose
When that occurs, some glucose will be excreted into the urine
(glucosuria)
This is the cause of urinary glucose in diabetes mellitus
Note: small amounts of glucose may spill into the urine when plasma
concentrations are as low as 180 mg/deciliter. This occurs because some
of the nephrons have lower tubular maximum rates than others
• Second example 2: Water reabsorption
o Due to osmosis, but the osmotic gradients are set up by Na active transport
• There are maximum rates (tubular maximums) for reabsorption by active transport or
secondary active transport
• Maximum transport rate is limited by the number of pump or carrier molecules in the cell
membrane
22
• The kidney takes advantage of the osmotic pressure difference between tubule fluid and
interstitial fluid to move water out of the tubule
• By changing the permeability of the collecting duct the kidney is able to make
concentrated or dilute urine by osmosis
More Information
Johann Koeslag of the University of Stellenbosch, Tygersberg, South Africa, has a nicely
illustrated internet essay, Kidney Physiology in a Nutshell.
If you develop a passion for the kidney (many physiologists do!) someday you will want to read
this book on kidney evolution by Homer Smith:
• Homer Smith. From Fish to Philosopher. Boston: Little, Brown & Co., 1953.
23
Return to Lecture Note Index / Return to Homepage /Next Lecture
• Working muscle can increase its O2 consumption by an enormous factor (up to 100 X for
individual muscles)
o O2 consumption by the whole body increases 20-25X in athletes
o Requires rapid O2 delivery and fast removal of waste and heat
• Exercise involves much more than the muscular and skeletal systems
o Cardiovascular & respiratory systems deliver O2 & fuel, remove wastes & heat
o Skin gets rid of heat through radiation & evaporation
o Nervous & endocrine systems monitor & coordinate the other systems
• Chemical energy in the body is stored mainly as ATP , glycogen and triglycerides
o ATP (and creatine phosphate = CP) can be used very rapidly but we have only
tiny amounts- enough for about 10 sec. (good for sprinting, jumping, lifting)
o Glycogen is stored in the muscles and liver and there is enough for approximately
2 hours- "hitting the wall" when running a marathon is caused by running out of
glycogen
o We have lots of energy stored as lipids (triglycerides)- the amount varies from
person to person, but there is enough for many days
24
Time Distance
enough for about enough to go
ATP & CP fastest
10 sec about 100 yards
enough for glycolysis
Carbohydrates enough to go
about medium fast;
(glycogen) about 20 miles
2hrs respiration slower
enough for
Lipids enough to go
about very slow
(triglycerides) about 1000 miles
40 days
• We can exercise vigorously for only a few seconds using the stored ATP & creatine
phosphate
• Any exercise over a few seconds duration is a "pay as you go" system
o Requires aerobic respiration to provide enough energy
o Anaerobic glycolysis gives only 2 ATPs/glucose while aerobic respiration gives
36 ATPs/glucose
o O2 consumption goes up with intensity of exercise because aerobic metabolism
must be used to generate ATP
o Glycogen is the main initial fuel source
Sympathetic nervous systemcauses glycogen breakdown to glucose
Liver releases glucose into the blood to supply muscles & brain
o As exercise continues more and more fat is used for fuel
Triglycerides hydrolyzed to produce fatty acids & glycerol
• Maximum sustained oxygen consumption (VO2max) is a good measure of endurance in
athletes
Both Stroke Volume and Heart Rate Go Up, Increasing Cardiac Output
• In exercise the heart rate rises from about 60 beats/min to close to 200 beats/min
25
• The stroke volume also rises, from about 80 mL/beat to about 150 mL/beat (these values
are for athletes)
• Combined, these adjustments can increase cardiac output (CO) from approximately 5
L/min to nearly 30 L/min
• CO is controlled by the autonomic nervous system and by hormones like epinephrine
• The increased CO in exercise will cause the systolic blood pressure to rise (to about 180
mm Hg); the diastolic pressure usually does not change
• The cardiovascular system may be the limiting factor in endurance exercise
• Limits to CO increase:
• No matter how much you train you cannot exceed upper limits on HR and SV
o HR is limited to about 200 beats/min- if the beat is faster there will not be enough
filling time
o SV is limited by sarcomere length-
Strongest contraction is at intermediate length
If heart muscle is stretched too much by overfilling the contraction will be
weaker
• Blood flow can be increased by raising the blood pressure and by lowering resistance to
flow
• Resistance to flow is controlled by muscle sphincters which open (vasodilation) and close
(vasoconstriction) the arterioles
• In exercise more blood is shifted to muscle and heart tissue; less blood goes to the viscera
and tissues not needed at the moment:
• Flow to skin is initially reduced but is later increased to get rid of excess heat
26
Increased Blood Flow to the Skin and Sweating Help to Get Rid of Excess Heat
Extracellular Water Must be Closely Regulated to Control Blood Pressure and Edema
• Drinking experiment:
o If you drink a liter of water (or beer) the kidneys will produce large amounts of
urine and eliminate it in a short period of time to keep the plasma volume constant
o If you drink a liter of saline (or drink beer with pretzels) urine production is low
and the water is retained for a much longer period of time
o Longer retention is due to the osmotic pressure of the saline:
Pure water lowers the osmotic pressure of the plasma and inhibits ADH
release (see below)
The saline solution raises the plasma osmotic pressure- this triggers ADH
release
27
Data from Homer Smith. Principles of Renal Physiology. Oxford
University Press, 1956.
• Over a long period of time the Na in the saline solution will be slowly excreted and this
will take water with it by osmosis; the liter of saline will also be eliminated, but much
more slowly
• Water regulation is much faster than Na regulation
The Kidney Can Adjust Extracellular Water by Making Either Concentrated or Dilute
Urine
• If there is too much extracellular water the kidney will correct the situation by making
large amounts of dilute urine (low specific gravity)
• If the person is dehydrated (too little extracellular water) the kidney will compensate by
producing small amounts of concentrated urine (high specific gravity)
• The outer layer of the kidney is isotonic with the blood: ~300 milliosmoles/liter
• The innermost layer (medulla) is very hypertonic: ~1200 milliosmoles/liter
28
• Osmotic gradient is produced by a countercurrent mechanism located in the loop of
Henle
o The countercurrent mechanism is based upon the Na pump; by pumping large
quantities of Na into the interstitial fluid in the medulla a very high concentration
is built up
o Click to see more details of the countercurrent mechanism
The Kidney Uses Osmosis in the Collecting Duct to Control the Concentration and Volume
of Urine
• The concentration of the urine is adjusted in the collecting ducts of the kidney. The
collecting ducts pass through tissue with a very high osmotic pressure in the medulla.
Water will be sucked out of the tubules by osmosis if the tubules are permeable.
• As the urine passes into the collecting duct it first passes through a region of isotonic
osmotic pressure (300 milliosmoles/liter) and then through a region of hypertonic
osmotic pressure (up to 1200 milliosmoles/liter)
• If the collecting duct has low water permeability the dilute urine in the kidney tubule
passes through with little uptake of water
o This produces large amounts of dilute urine (diuresis)
• If the collecting duct has high water permeability much of the water will be reabsorbed
from the collecting duct into the interstitial fluid
o This produces small amounts of concentrated urine (antidiuresis)
ADH Controls Kidney Osmosis by Inserting Water Pores into the Collecting Duct
• The permeability of the collecting duct is determined by water pores (aquaporin-2) which
are under the control of antidiuretic hormone (ADH- also called vasopressin) from the
posterior pituitary
• The water pores are made by the cells lining the collecting duct
• Pores are stored in vesicles called endosomes and are inserted when needed
• If ADH is present they are inserted into the cell membranes facing the tubule
• If ADH is low the channels are removed from the membranes (down-regulated)
If ADH is High the Kidney Makes Concentrated Urine and Conserves Water
• If a person has recently consumed a lot of water the ADH secretion will be low
29
• Water channels will be down-regulated from the collecting duct
• Less water will be reabsorbed
• The increased urine production will remove the excess water
• Diabetes insipidus is the continuous production of large amounts of watery urine (5-10
L/day)
• The urine does not contain sugar, as it does in diabetes mellitus
• ADH mechanism can fail in 2 ways:
o Posterior pituitary does not secrete enough ADH (blood ADH will be low)
o Kidney does not respond to ADH (nephrogenic: blood ADH will be normal)
30
• The kidney can also adjust urine Na concentration by reabsorption in the distal tubule
• This activity is under control of the adrenal cortical hormone aldosterone
• Aldosterone acts by turning on genes (transcription), so its stimulation of Na retention is
relatively slow
o Causes production of Na pump molecules
• Aldosterone is released from the adrenal cortex mainly in response to a lowered blood
pressure
• Renin-angiotensin mechanism:
o Low blood pressure causes the juxtaglomerular cells of the kidney to secrete an
enzyme called renin into the blood
o Renin converts a protein called angiotensinogen (produced by the liver) into
angiotensin I
o Angiotensin I is converted to angiotensin II by angiotensin converting enzyme
(ACE), which is found in capillary walls
ACE inhibitors are used to lower blood pressure
o Angiotensin II causes the adrenal cortex to secrete more aldosterone into the
blood
• Aldosterone causes distal tubule cells of the kidney to produce more Na pumps
• More Na is pumped out of the distal tubule and enters the blood (increased Na retention)
• Angiotensin II has several other activities which act to raise the blood pressure:
o It stimulates the hypothalamus to increase thirst and ADH secretion
o It stimulates the cardiovascular center of the medulla to increase the cardiac
output
o It causes vasoconstriction of arterioles
31
• Note 1: blood factors are shown on the left of the diagram
• Note 2: this diagram does not show effects of angiotensin II on the arterioles,
hypothalamus and cardiovascular center
Atrial Natriuretic Peptide (ANP) Causes Loss of Both Sodium and Water
• If the blood volume is too high blood pressure goes up and the atria are stretched more
than normal as blood enters the heart
• This causes the release of a peptide, ANP, by atrial cells
• ANP causes the body to lose both Na and water, restoring the blood volume to normal
o Increases GFR
o Inhibits aldosterone, renin and ADH secretion
32
Lecture: Physiology of Blood
VOLUME LAYER
C. Characteristics of Blood
33
b. carbon dioxide from body cells to lungs
c. nutrients from GI tract to body cells
d. nitrogenous wastes from body cells to kidneys
e. hormones from glands to body cells
3. Protection
A. Structure
34
i. infants 14-20 grams/l00 ml
ii adult female 12-16 grams/100 ml
iii adult male 13-18 grams/l00 ml
2. states of hemoglobin
hemocytoblast ->
proerythroblast ->
early (basophilic) erythroblast ->
late (polychromatophilic) erythroblast ->
(hemoglobin) normoblast -> (nucleus ejected when enough hemoglobin)
reticulocyte -> (retaining some endoplasmic reticulum)
ERYTHROCYTE
3. Regulation of Erythropoiesis
35
1. Less RBCs from bleeding
2. Less RBCs from excess RBC destruction
3. Low oxygen levels (high altitude, illness)
4. Increased oxygen demand (exercise)
1. Anemias - a symptom that results when blood has lower than normal
ability to carry oxygen
b. Decrease in Hemoglobin
36
i. thalassemia - easily ruptured RBCs (Greek & Italian
genetic link)
B. Granulocytes - granules in cytoplasm can be stained with Wright's Stain; bilobar nuclei;
10-14 micron diameter; all are phagocytic cells (engulf material)
37
f. HIGH poly count --> likely infection
38
a. produced by Macrophages and T lymphocytes
EOSINOPHIL }
NEUTROPHIL } (0.5 to 9 day lifespan)
BASOPHIL }
E. Disorders of Leukocytes
A. General Characteristics
39
1. very small, 2-4 microns in diameter
2. approximately 250-500,000 per cubic millimeter
3. essential for clotting of damaged vasculature
4. thrombopoietin - regulates platelet production
B. Formation of Platelets
hemocytoblast->
myeloid stem cell->
megakaryoblast->
promegakaryocyte->
megakaryocyte-> (large multilobed nucleus)
platelets (anucleated parts of megakaryocyte cytoplasm)
A. General Characteristics
A. General Characteristics
B. Vascular Spasms
40
a. compression of vessel by escaping blood
b. injury "chemicals" released by injured cells
c. reflexes from adjacent pain receptors
41
Ca++ & thrombin -> Factor XIII (fibrin stabilizer)
B. Bleeding Disorders
42
2. impaired liver function - lack of procoagulants (Clotting Factors) that are
made in liver a. vitamin K - essential for liver to make Clotting Factors for
coagulation
A. Transfusion of Blood
1. whole blood transfusion - all cells and plasma; anticoagulants (citrate and
oxalate salts) used
2. packed red blood cells - most of the plasma has been removed prior to
transfusion
43
c. hemolysis - after clumping, RBCs may rupture, releasing
hemoglobin, harming kidney
i. dilute hemoglobin, administer diuretics
44
i. prevents physical entry of microorganisms
ii. first line of defense
2. Phagocytes, antimicrobial proteins, inflammation
i. activated by chemical signals when external defenses are penetrated
ii. Second line of defense
B. Adaptive or Specific system
1. Main components are the B and T lymphocytes
i. B-lymphocytes involved in humoral or antibody-mediated immunity
ii. T-lymphocytes involved in cellular or cell-mediated immunity
2. Takes considerable time but is highly specific
i. this is the body’s third line of defense
C. Functional System
1. has organs that are involved in the immune response but involves trillions of
individual immune cells
2. the immune system confers immunity which is resistance to disease
C. Internal Defenses
1. Nonspecific and consists of phagocytes, natural killer cells, antimicrobial
45
proteins, fever, and the inflammatory response which includes macrophages,
mast cells, and all types of white blood cells.
2. Phagocytes
i. cells that engulf or “eat” pathogens
ii. mainly macrophages
a. derived from monocytes which leave the bloodstream and enter
tissue and enlarge.
b. can roam tissues search for cellular debris or “foreign
invaders” like alveolar macrophages of the lungs or dendritic
cells of the epidermis.
c. can be fixed like Kupffer cells in the liver or microglia of the
brain
iii. neutrophils
a. most abundant type of white blood cell
b. may become phagocytic upon exposure to infectious material
c. secrete defensins, which are antibiotic-like chemicals
d. can release oxidizing and bleach-like chemicals which can
destroy cells, including themselves
e. prolonged activity may cause normal tissues to become
cancerous
iv. eosinophils
a. weak phagocytes but are important against parasitic worms
b. discharges destructive contents of cytoplasmic granules
v. mast cells
a. involved in allergies but have some phagocytic capabilities
3. Mechanism of Phagocytosis
i. Ameoba-like digestion
phagocyte engulfs particle using flowing cytoplasmic extensions
the particle is enclosed within a membrane-lined vacuole called a phagosome
a lysosome fuses with the phagosome to form a phagolysosome
pathogen killed and digested within the phagolysosome
indigestible waste is removed by exocytosis
ii. requires adherence of the particle to the phagocyte
a. carbohydrate signatures
b. pneumococcus has a capsule which makes adherence difficult
c. opsonization, which is the coating of foreign particles with
complement proteins and antibodies, increases adherence
iii. some pathogens can survive lysosomal enzymes and can multiply
within the vacuole.
a. respiratory burst can be activated by adaptive immune system
chemicals that produce free radicals, like nitric oxide, which
can kill cells.
4. Natural Killer Cells
i. in the blood and lymph
ii. can kill and lyse cancer cells and virus-infected body cells
iii. belong to the group large granular lymphocytes
46
iv. recognize surface sugars but are fairly nonspecific
v. not phagocytic, but release cytolytic chemicals called perforins
vi. secrete chemicals that enhance the inflammatory response
5. Inflammation
i. triggered by body tissue injuries like physical trauma, heat, irritating
chemicals, infection by viruses, fungi, and bacteria.
ii. functions to:
a. prevents spread of damaging agents
b. disposes of cell debris and pathogens
c. sets the stage for repair processes
iii. signs of inflammation are redness, heat, swelling, pain, and sometimes
impairment of function.
iv. begins with the release of inflammatory chemicals called
inflammatory mediators into the extracellular fluid
a. can come from injured tissue cells, phagocytes, lymphocytes,
mast cells, and blood proteins
v. main inflammatory mediators are histamine, kinins, prostaglandins,
complement, and cytokines
a. cause vasodilation and hyperemia, which is congestion with
blood, that is responsible for the redness and heat
b. increase permeability of local capillaries
i. fluid containing proteins like clotting factors and
antibodies, called exudates, flows from the bloodstream
into tissue spaces
ii. local edema occurs and pain is triggered
vi. edema can be beneficial
a. helps to dilute harmful substances that may be present
b. brings in large quantities of oxygen and nutrients needed for
repair.
c. allows entry of clotting proteins which forms a fibrin mesh that
prevents the spread of harmful agents.
vii. increases the production of β -defensins, which are antibiotic-like
chemicals.
6. Phagocyte mobilization
i. sequence:
mast cells neutrophils macrophages
ii. leukocytosis is first and chemicals called leukocytosis-inducing factors
are released from injured cells to promote neutrophil release from red
bone marrow.
iii. margination is the process of cell adhesion molecules (CAMs) of
neutrophils binding to cell adhesion molecules (CAMs) called
selectins of the endothelial cells of capillary walls causing the
neutrophils to cling to the capillary wall.
iv. diapedesis is the process of neutrophils emigrating through the
capillary walls to the site of inflammation.
v. chemotaxis is the attraction of neutrophils and other white blood cells
47
to the site of injury due to inflammatory chemicals called chemotactic
agents.
vi. monocytes become macrophages about 8-12 hours after entering the
tissues. Macrophages are dominant at sites of chronic inflammation.
7. Pus is a mixture of dead or dying neutrophils, broken-down tissue cells, and
living and dead pathogens.
8. Abscesses are sacs of pus walled off by collagen fibers
9. Infection granulomas are tumorlike growths containing macrophages infected
by pathogens “hiding” within it surrounded by uninfected macrophages and an
outer fibrous capsule.
10. Antimicrobial proteins
i. attack microorganisms directly or inhibit their ability to reproduce
ii. interferon
a. different types like γ , α , and β -interferon
b. are small proteins which “interferes” with viral replication.
c. not virus specific
d. γ comes from lymphocytes
e. α comes from most other leukocytes
f. β comes from fibroblasts
g. activates macrophages and mobilizes natural killer cells
h. play an anticancer role
i. α is used to treat genital warts and can combat Hep C
11. Complement system
i. group of at least 20 plasma proteins that destroy foreign substances by
lysis when activated.
ii. amplifies the inflammatory process
iii. there is a classical pathway and an alternative pathway that both lead to
the activation of C3, one of the complement proteins, which is then
cleaved into two subunits which can cause inflammation and
opsonization.
iv. MAC is the membrane attack complex which inserts into the
membrane of the target cell and inhibits the cell’s ability to eject Ca+2
and causes lysis
12. Fever
i. body temperature is controlled by hypothalamic neurons and is set to
about 36.2 °C
ii. fever occurs when pyrogens, chemicals secreted by leukocytes and
macrophages exposed to foreign matter, resets the neurons higher.
iii. high fevers can denature enzymes
iv. fevers are helpful because it speeds up the metabolic rate of tissue
cells and cause the liver and spleen to contain iron and zinc, which
bacteria require in large amounts to multiply
Lecture: Heart Physiology
48
fairly short semi-spindle shapebranched,
interconnected
connected (intercalated discs) electrical link
(gap junction) common contraction
(syncytium) 1 or 2 central nuclei
dense "endomysium" high vasculature
MANY mitochondria (25% space) almost
all AEROBIC (oxygen) myofibers fuse at
ends T tubules wider, fewer
very long
cylindrical shape
side-by-side
no tight binding
no gap junctions
independent contract
multinucleated
light "endomysium"
medium vasculature
less mitochondria (2%)
aerobic & anaerobic
myofibers not fused
T tubules at A/I spot
49
II. Mechanism of Contraction of Contractile Cardiac Muscle Fibers
1. All-or-None Law - Gap junctions allow all cardiac muscle cells to be linked
electrochemically, so that activation of a small group of cells spreads like a wave
throughout the entire heart. This is essential for "synchronistic" contraction of the
heart as opposed to skeletal muscle.
a. K+ leak channels allow K+ OUT of the cell more slowly than in skeletal muscle
b. Na+ slowly leaks into cell, causing membrane potential to slowly drift up to the
threshold to trigger Ca++ influx from outside (-40 mV)
c. when threshold for voltage-gated Ca++ channels is reached (-40 mV), fast calcium
channels open, permitting explosive entry of Ca++ from of the cell, causing sharp
rise in level of depolarization
a. sinoatrial node (SA node) "the pacemaker" - has the fastest autorhythmic rate (70-
80 per minute), and sets the pace for the entire heart; this rhythm is called the
sinus rhythm; located in right atrial wall, just inferior to the superior vena cava
b. atrioventricular node (AV node) - impulses pass from SA via gap junctions in
about 40 ms.; impulses are delayed about 100 ms to allow completion of the
contraction of both atria; located just above tricuspid valve (between right atrium
& ventricle)
e. Purkinje fibers - within the lateral walls of both the L and R ventricles; since left
ventricle much larger, Purkinjes more elaborate here; Purkinje fibers innervate
“papillary muscles” before ventricle walls so AV can valves prevent backflow
A. General Concepts
1. glomerular filtration
2. tubular reabsorption
3. tubular secretion
A. Filtration Membrane
1. hydrostatic pressure - forces 1/5 of blood fluid through capillary' walls into
glomerular capsule
2. filtration membrane - has three parts
a. fenestrated capillary endothelium (prevents passage of blood cells)
b. basal membrane (allows most solutes but larger proteins)
c. visceral membrane of glomerular capsule
4. renin-angiotensin mechanism
A. Overview of Reabsorption
1. filtrate - all fluid and its solutes pushed into the capsule
2. urine - filtrate minus reabsorbed substances + secreted substances
3. route of reabsorption (transepithelial process)
2. transport maximum (Tm) when "carrier proteins" for specific solute becomes
saturated and cannot carry the substance across the membrane
D. Nonreabsorbed Substances
1. urea, creatinine, uric acid - most is not reabsorbed because of the following
reasons
c. atrial natriuretic factor (ANF) - reduces Na+ permeability, less water (in
response to high B.P.)
1. Water moves out along Descending Limb of the Loop of Henle, creating 1200
mosm urine at the base
2. Na+Cl- moves out along the Ascending Limb of the Loop of Henle, creating 100
mosm urine at distal end. This salt helps pull more water out of the Descending
Limb in positive feedback mechanism.
4. Vasa recta (capillaries around Loop of Henle) have no Net Effect on water/salt
balance
1. When water removal is needed, no ADH is released, so that the Distal and
Collecting Tubules will not actively transport Na+ out; no water moves out
2. Urine may be as low as 50 mosm
A. Renal Clearance (RC) - the rate at which the kidney can remove a substance from the
blood
RC = U/P X V
B. Chemical Composition
1. 95% water
2. 5% solutes - urea (breakdown of amino acids); uric acid; creatinine
Lecture: Physiology of Vision
1. electromagnetic radiation
1. light refraction - light will bend when it passes from one medium
(air) into another (lens) e.g. pencil in glass of water
a. real image - image at focal point of convex lens ---> inverted &
reversed
i. rods - pigment discs stacked like pennies all the way to the base,
membranes are DISTINCT from the plasma membrane
ii. cones - pigment discs taper off toward the base, membranes are
CONTINUOUS with the plasma membrane
C. Excitation of Rods
D. Excitation of Cones
1. photopsins - 3 distinct pigments in cones are sensitive to 3
different parts of visible spectrum
3. color blindness inherit gene for one of the photon proteins that
is deficient (mainly male), most common are red and green
mutations
A. binocular vision - two eyes have overlapping regions of the visual field, so
that the same point is seen from slightly different angles
air -->
external auditory canal -->
tympanic membrane (ear drum) -->
ossicles (malleus, incus, stapes.) -->
oval window of cochlea -->
vibration of cochlear fluid -->
basilar membrane of cochlea
1. superior olivary nucleus - first point where sound from both ears
come together
a. relative intensity - the amplitude of sound waves hitting the
different ears
b. relative timing - the difference in timing in which a sound
reaches both ears
1. vestibule - bony cavity of the inner ear between the cochlea and the
semicircular canals
a. saccule and utricle - smaller sacs housed within the
vestibule
b. maculae - patch of "supporting cells" and "hair cells" along
the utricles and saccules
i. hair cells - like hair cells of basilar membrane, respond
when bent
c. otolithic membrane - jelly-like sheet that abuts the
"stereocilia" of the hair cells
i. otoliths - "ear stones" that rest on top of the otolithic
membrane
1. electromagnetic radiation
1. light refraction - light will bend when it passes from one medium
(air) into another (lens) e.g. pencil in glass of water
a. real image - image at focal point of convex lens ---> inverted &
reversed
i. rods - pigment discs stacked like pennies all the way to the base,
membranes are DISTINCT from the plasma membrane
ii. cones - pigment discs taper off toward the base, membranes are
CONTINUOUS with the plasma membrane
C. Excitation of Rods
3. color blindness inherit gene for one of the photon proteins that is
deficient (mainly male), most common are red and green mutations
A. binocular vision - two eyes have overlapping regions of the visual field, so
that the same point is seen from slightly different angles
1. bilayer of phospholipids
A. General Features
l mole H = 1 gram H
1 mole C = 12 grams C
1 mole NaCl = 58 grams NaCl
1 mole C6H12O6 = 180 grams C6H12O6
58 grams NaCl/l liter water = 1 mole NaCl/liter = 1 Molar NaCl (lM NaCl)
180 g Glucose/1 liter water = 1 mole glucose/liter = 1 Molar glucose (1M Glucose)
particles in a solution
i. 1 molar Glucose = 1 osmol Glucose
ii.1 molar NaCl = 2 osmol NaCl
*the larger the difference in concentrations between the INSIDE and OUTSIDE, the
larger the osmotic pressure (driving force is greater)
d. hydrostatic pressure - pressure of cell wall in plant cells that balances the
osmotic pressure, preventing more water from entering the cell
against diffusion)
b. Na+-K+ ATPase Pump - creates ion concentration gradient for cell [Na+]OUT
HIGH; [K+]IN HIGH
i. ATP is used by this pump to move 3 Na+ out of the cell and bring 2 K+
into the cell
ii. Na+ will want to move INTO cell; K+ will want to move OUT of cell
2. bulk transport - cell membrane pouching process
a. exocytosis - cell vesicle moves to
membrane with contents, merges, then
releases material
i. hormone/neurotransmitter release; mucus secretion; expulsion of
extracellular proteins (collagen, elastin, matrix)
insulin, low density lipoproteins (LDL), and Fe++ can be ligands for such receptors
III. The Resting Membrane Potential (voltage across the membrane)
A. voltage - energy that results from separation of charges (also called potential
difference - potential)
1. The Na+-K+ ATPase Pump creates concentration gradients for both Na+ and K+
a. [Na+]OUT > [Na+]IN
b. [K+]IN > [K+]OUT
3. Na+ Channels normally closed so that Na+ cannot easily move back into the
cell.
5. The net movement of Na+ and leaking of K+ to the outside of the cell causes a
POTENTIAL DIFFERENCE (voltage) across the membrane.
A. General Features
B. Ultrastructure of Myofibrils
¼
1. muscle cell contains many parallel myofibrils
2. myofibrils have DARK bands (A bands) and LIGHT bands (I bands) that
cause "striated" appearance of muscle
3. A band and I band result from the arrangement of overlapping and non-
overlapping regions of two types of myofilaments
Each muscle cell (fiber) is composed of many myofibrils. Each myofibril contains
hundred of accordion-like sarcomeres laid end-to-end. Muscle contraction occurs
when the sarcomeres contract by the sliding motion of actin and myosin filaments.
b. Calcium Sequesters - bind Ca++ in the cell so it will not form Calcium
Phosphate crystals
A. Motor Unit - a single motor neuron and all of the muscle cells stimulated by
it
muscle
3. Series-Elastic Elements
a. sheath around the muscle and the connective tissue tendons that attach
muscle to bone
b. "stretching" of non-contractile parts allows time for muscle to produce a
tetanic contraction
1. lack of use can result in loss of size (atrophy) and strength of a muscle
2. denervation - lack of nervous stimulation can also cause severe atrophy
VII.Muscle Metabolism
2. contractures - continuous contracted state of the muscle ("heads" are not released)
3. oxygen debt - oxygen must be "paid back" in order to restore muscle to original
rested state:
B. Blood Pressure - the FORCE exerted on the wall of a blood vessel by the
blood contained within (millimeters of Mercury; mm Hg)
blood pressure = the systemic arterial pressure of large vessels of the body (mm Hg)
2. tube length - the longer the vessel, the greater the drop in pressure
due to friction
L ventricle -->120 mm Hg
arteries -->120 - 60 mm Hg
arterioles -->60 - 40 mm Hg
capillaries -->40 - 20 mm Hg
venous -->20 - 10 mm Hg
R atrium -->10 - 0 mm Hg
CO = SV (ml/beat) x HR (beats/min)
B. Peripheral Resistance
C. Blood Volume
baroreceptors/chemoreceptors/brain -->
afferent nerve fibers -->
medulla (vasomotor center) -->
vasomotor (efferent) nerve fibers -->
smooth muscle of arterioles
D. Baroreceptors
E. Chemoreceptors
2. renin-angiotensin mechanism
i. kidney disorders
ii. endocrine (hormone) disorders
iii. arteriosclerosis
A. General Features
B. Fluid Movements
C. Circulatory Shock
1. circulatory shock - blood pressure gets so low that blood will not
flow adequately
a. water (97-99.5%)
b. electrolytes: Na+, K+, Cl-, PO4-
c. mucin - protein that forms thick, slimy mucus
d. IgA antibodies - immune defense
e. lysozyme - antibacterial enzyme
f. salivary amylase - starts breakdown of carbo's
2. control of salivation:
ingestion of foodstuffs
activate chemoreceptors and pressoreceptors
salivatory nuclei (pons & medulla)
PARASYMPATHETIC nerve activation
Facial (VII) and Glassopharyngeal (IX) nerves
secretion by salivary glands
B. Mechanical Processes
2. gastric phase
3. intestinal phase
D. Defecation
B. Carbohydrate Digestion
1. monosaccharides - "monomers" such as glucose, fructose, and
galactose
2. disaccharides - sucrose (table sugar), lactose (milk sugar), and
maltose (grain sugar)
3. polysaccharides - starch (grains), glycogen (muscle)
4. carbohydrate hydrolyzing enzymes
a. salivary amylase - produces "oligosaccharides"
b. pancreatic amylase - in small intestine
c. intestinal enzymes - dextranase & glucoamylase (> 3
sugars), maltase, sucrase, and lactase
5. lactose intolerance - decreased ability to digest lactose in the diet
(use "lactase" supplements)
C. Protein Digestion
A. General Features
B. Carbohydrate Absorption
a. "carrier molecule" has binding sites for both sugar and Na+;
relies on Na+ gradient
D. Lipid Absorption
1. micelles - tiny balls of fats that result from bile salt emulsification
and "lecithin"
F. Vitamin Absorption
G. Electrolyte Absorption
H. Water Absorption
I. Malabsorption of Nutrients
C. Internal Defenses
1. Nonspecific and consists of phagocytes, natural killer cells,
antimicrobial
proteins, fever, and the inflammatory response which includes
macrophages,
mast cells, and all types of white blood cells.
2. Phagocytes
i. cells that engulf or “eat” pathogens
ii. mainly macrophages
a. derived from monocytes which leave the bloodstream
and enter
tissue and enlarge.
b. can roam tissues search for cellular debris or “foreign
invaders” like alveolar macrophages of the lungs or
dendritic
cells of the epidermis.
c. can be fixed like Kupffer cells in the liver or microglia
of the
brain
iii. neutrophils
a. most abundant type of white blood cell
b. may become phagocytic upon exposure to infectious
material
c. secrete defensins, which are antibiotic-like chemicals
d. can release oxidizing and bleach-like chemicals which
can
destroy cells, including themselves
e. prolonged activity may cause normal tissues to become
cancerous
iv. eosinophils
a. weak phagocytes but are important against parasitic
worms
b. discharges destructive contents of cytoplasmic granules
v. mast cells
a. involved in allergies but have some phagocytic
capabilities
3. Mechanism of Phagocytosis
i. Ameoba-like digestion
phagocyte engulfs particle using flowing cytoplasmic extensions
the particle is enclosed within a membrane-lined vacuole called a
phagosome
a lysosome fuses with the phagosome to form a phagolysosome
pathogen killed and digested within the phagolysosome
indigestible waste is removed by exocytosis
ii. requires adherence of the particle to the phagocyte
a. carbohydrate signatures
b. pneumococcus has a capsule which makes adherence
difficult
c. opsonization, which is the coating of foreign particles
with
complement proteins and antibodies, increases
adherence
iii. some pathogens can survive lysosomal enzymes and can
multiply
within the vacuole.
a. respiratory burst can be activated by adaptive immune
system
chemicals that produce free radicals, like nitric oxide,
which
can kill cells.
4. Natural Killer Cells
i. in the blood and lymph
ii. can kill and lyse cancer cells and virus-infected body cells
iii. belong to the group large granular lymphocytes
iv. recognize surface sugars but are fairly nonspecific
v. not phagocytic, but release cytolytic chemicals called perforins
vi. secrete chemicals that enhance the inflammatory response
5. Inflammation
i. triggered by body tissue injuries like physical trauma, heat,
irritating
chemicals, infection by viruses, fungi, and bacteria.
ii. functions to:
a. prevents spread of damaging agents
b. disposes of cell debris and pathogens
c. sets the stage for repair processes
iii. signs of inflammation are redness, heat, swelling, pain, and
sometimes
impairment of function.
iv. begins with the release of inflammatory chemicals called
inflammatory mediators into the extracellular fluid
a. can come from injured tissue cells, phagocytes,
lymphocytes,
mast cells, and blood proteins
v. main inflammatory mediators are histamine, kinins,
prostaglandins,
complement, and cytokines
a. cause vasodilation and hyperemia, which is congestion
with
blood, that is responsible for the redness and heat
b. increase permeability of local capillaries
i. fluid containing proteins like clotting factors and
antibodies, called exudates, flows from the
bloodstream
into tissue spaces
ii. local edema occurs and pain is triggered
vi. edema can be beneficial
a. helps to dilute harmful substances that may be present
b. brings in large quantities of oxygen and nutrients needed
for
repair.
c. allows entry of clotting proteins which forms a fibrin
mesh that
prevents the spread of harmful agents.
vii. increases the production of β -defensins, which are antibiotic-
like
chemicals.
6. Phagocyte mobilization
i. sequence:
mast cells neutrophils macrophages
ii. leukocytosis is first and chemicals called leukocytosis-inducing
factors
are released from injured cells to promote neutrophil release
from red
bone marrow.
iii. margination is the process of cell adhesion molecules (CAMs)
of
neutrophils binding to cell adhesion molecules (CAMs) called
selectins of the endothelial cells of capillary walls causing the
neutrophils to cling to the capillary wall.
iv. diapedesis is the process of neutrophils emigrating through the
capillary walls to the site of inflammation.
v. chemotaxis is the attraction of neutrophils and other white
blood cells
to the site of injury due to inflammatory chemicals called
chemotactic
agents.
vi. monocytes become macrophages about 8-12 hours after
entering the
tissues. Macrophages are dominant at sites of chronic
inflammation.
7. Pus is a mixture of dead or dying neutrophils, broken-down tissue cells,
and
living and dead pathogens.
8. Abscesses are sacs of pus walled off by collagen fibers
9. Infection granulomas are tumorlike growths containing macrophages
infected
by pathogens “hiding” within it surrounded by uninfected macrophages
and an
outer fibrous capsule.
10. Antimicrobial proteins
i. attack microorganisms directly or inhibit their ability to
reproduce
ii. interferon
a. different types like γ , α , and β -interferon
b. are small proteins which “interferes” with viral
replication.
c. not virus specific
d. γ comes from lymphocytes
e. α comes from most other leukocytes
f. β comes from fibroblasts
g. activates macrophages and mobilizes natural killer cells
h. play an anticancer role
i. α is used to treat genital warts and can combat Hep C
11. Complement system
i. group of at least 20 plasma proteins that destroy foreign
substances by
lysis when activated.
ii. amplifies the inflammatory process
iii. there is a classical pathway and an alternative pathway that both
lead to
the activation of C3, one of the complement proteins, which is
then
cleaved into two subunits which can cause inflammation and
opsonization.
iv. MAC is the membrane attack complex which inserts into the
membrane of the target cell and inhibits the cell’s ability to
eject Ca+2
and causes lysis
12. Fever
i. body temperature is controlled by hypothalamic neurons and is
set to
about 36.2 °C
ii. fever occurs when pyrogens, chemicals secreted by leukocytes
and
macrophages exposed to foreign matter, resets the neurons
higher.
iii. high fevers can denature enzymes
iv. fevers are helpful because it speeds up the metabolic rate of
tissue
cells and cause the liver and spleen to contain iron and zinc,
which
bacteria require in large amounts to multiply
Lecture: Physiology of Respiration
A. Relationships of Pressure
B. Inspiration
1. diaphragm muscle contracts, increasing thoracic cavity size in the
superior-inferior dimension
C. Expiration
2. lung elasticity - the ease with which lungs can contract to their
normal resting size (exhalation) a. emphysema - decreases
elasticity
B. Respiratory CAPACITIES
1. anatomical dead space - all areas where gas exchange does not
occur (all but alveoli)
2. alveolar dead space - non-functional alveoli
3. total dead space - anatomical + alveolar
1. partial pressure - the "part" of the total air pressure caused by one
component of a gas
2. solubility - the ease with which a certain gas will "dissolve" into a
liquid (like blood plasma)
3. harmful - SCUBA divers may suffer the "bends" when they rise
too quickly and Nitrogen gas "comes out of solution" and forms
bubbles in the blood
a. Partial Pressure of O2
b. temperature
c. blood pH (acidity)
d. concentration of “diphosphoglycerate” (DPG)
D. Effects of pH (Acidity)
2. Haldane Effect - the less oxygenated blood is, the more Carb Diox
it can carry
2. low shallow breaths --> HIGH Carb Diox --> LOW pH (higher
H+)
3. rapid deep breaths --> LOW Carb Diox --> HIGH pH (lower
H+)
C. Oxygen Effects
A. Exercise Effects
B. Lung Cancer
A. Fluid Compartments
B. Fluid Composition
A. Sodium (Na+) - 90% of solutes in the ECF; most important and prevalent
of all electrolytes
B. Aldosterone - released by adrenal cortex (renin-angiotensin)
C. Baroreceptors
F. Steroid Hormones
A. Importance of K+
A. Importance of Ca++
I. Inorganic Compounds
down molecules
homeostasis
C. Acids and Bases – H+ donors and H+ acceptors
released in stomach
HCl H+ + Cl-
urea (urine)
NH3 + H+ NH4+
H2O H+ + OH-
i. 1 of l07 water
molecules dissociate in pure H2O
ii. H+
concentration is 1/10,000,000 = l0-7
iii. pH = -log10[H+]
iv. pure water pH = -log10 [l0-7] = 7.0
4. Neutralization - acid and base combine HCl + NaOH H2O +
NaCl
H2CO3 HCO3- + H+
c. 6-carbon sugars
i. glucose - main monosaccharide in blood
ii. galactose - glucose isomer (OH changes)
iii. fructose - glucose isomer
4. Functions of Carbohydrates
a. glycerol, 2
fatty acid chains, and phosphate
b. "tail" - non-polar fatty acids (hydrophobic)
c. "head" - polar phosphate group (hydrophilic)
d. major component of the plasma membrane of cell
3. Steroids
a. ringlike structure
b. cholesterol -
precursor of all other steroids
i. easily dissolved in neutral fats
ii. essential to maintain membrane rigidity
c. other steroids derived from cholesterol
i. Vitamin D - sunlight; for bone growth
ii. sex hormones - estrogen, progesterone,
testosterone
iii. other hormones - cortisol (stress signal) and aldosterone (salt/water balance)
D. Proteins
a. Primary Structure
i.actual linear combination of amino
acids
b. Secondary Structure
i. alpha-helix: coiling of the polypeptide
ii. beta-pleated sheet: chains side by side
c. Tertiary Structure
i.secondary structures form 3-D shape
important for correct function
d. Quaternary Structure
i.two or more polypeptides together
ii. hemoglobin: 2 alpha and 2 beta
polypeps
3. Functions of Proteins
Fibrous Proteins
a. Structural
i. collagen - bone, tendon, ligaments
ii. keratin - hair, nails, skin
iii. elastin - trachea and joints
b. Movement
i. actin & myosin - muscle cells
ii. microtubules - cilia and flagella
Globular Proteins
a. Enzymes - Catalysis of Chemical Reactions
i. peroxidase - converts H2O2 to H2O
ii. amylase - breaks down starch to glucose
b. Transport
i. hemoglobin - binds and carries oxygen
ii. K+ Channel - allows K+ into a cell
c. pH Buffer
i. albumin - acid & base buffer in blood
d. Hormonal Function
i. insulin - regulates blood glucose level
ii. growth hormone - regulates human growth
e. Neurotransmitter
i. enkephalins - regulate pain in spinal cord
f. Immunity
i. antibodies - attach to foreign molecules
ii. complement proteins - enhance response
5. Denaturation of Proteins
Lecture: Homeostasis
I. Organization of Life
See Figure 1
Return
II. Basic Functions of Organisms
A. Maintenance of Boundaries - separation of organism
Physiology is the study of how organisms separate self and non-self; move;
respond to internal and external changes; digest, metabolize, and excrete
materials; reproduce; and grow.
This is achieved by maintaining a proper BALANCE both internally and with the
outside world.
IV. Homeostasis
external changes
general controls
"set point"
In Physiology, we study how each of the organ systems work to provide survival
needs of organism and maintain homeostasis of each of the essential variables
Lecture: Basic Chemistry
3. Forms of Energy
a.chemical energy - energy in chemical bonds
i. ATP (adenosine triphosphate) - stores energy
b. electrical energy - energy of separated charges
i. battery - + pole and - pole separate charge
ii. nervous impulse run just like a battery
c.mechanical energy - energy of matter in motion
i. bowling ball transfers energy to move pins
ii. muscle motion - ATP -> contraction of muscle
d. electromagnetic energy - energy traveling in waves (light, X-rays,
UV rays)
i. electromagnetic spectrum - visible light, UV light, radio
waves, X-rays
1. “Energy can change from one form to another, but it can never be
created or destroyed" (Total Energy In = Total Energy Out)
A. Atomic Particles
Mass Charge Characteristics
proton 1 +1 defines element
neutron 1 neutral defines isotopes
electron 0 -l determines element
bonding properties
See Figure 4
Return
Carbon-12 (99%) 6 6 12
Carbon-13 (0.9%) 6 7 13
Carbon-14 (0.1%) 6 8 14
See Figure 5
Return
H1 He2 SHELL l
2 e-
Li3 Be4 B5 C6 N7 08 F9 Ne10 SHELL28 e-
Na11 Mg12 Al13 Si14 P15 S16 Cl17 Ar18 SHELL3
8 e-
See Figure 6
Return
C. Chemical Bonds are formed so that each atom can have the outermost
V. Chemical Reactions
A + B AB (anabolic process)
amino acid 1 + amino acid 2 + .......... peptide (protein)
molecules
AB A + B (catabolic process)
glycogen ---> glucose + glucose + glucose +...........
AB + C A + BC
A + B C + D + ENERGY
A + B + ENERGY C
C. Chemical Equilibrium
1. Reversible Reactions
A + B AB and AB A + B
2. Chemical Equilibrium
A + B AB
H2O H+ + OH-
Return
Figure 2
Return
Figure 3
Return
Figure 4
Return
Figure 5
Return
Figure 6
Return