Lecture 9: Membrane Structure & Function

Cell Membranes are Primarily Phospholipid Bilayers

Cell membranes are phospholipid bilayers (2 layers)

• • • • •

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

Membranes Also Contain Proteins
• •

Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long Hydrophobic = doesn't like water = likes lipids

Membrane proteins have many functions: o receptors for hormones o pumps for transporting materials across the membrane o ion channels o adhesion molecules for holding cells to extracellular matrix o cell recognition antigens Why do you suppose the hydrophobic sections of membrane proteins are about 25 amino acids long? Discuss your answer.

All Molecules Move Continuously by Simple Diffusion

Heat energy causes molecules to move randomly

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 Substances Have a High Permeability Through Bilayer Membranes
• • • • •

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

The higher the partition coefficient the higher the permeability

Osmosis Moves Water Across Biological Membranes
• •

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.

Cells Swell in Hypotonic Solutions and Shrink in Hypertonic Ones
• • • •

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.

In Facilitated Diffusion Special Proteins Help Move Substances Across Membranes

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

Active Transport Uses Energy to Pump Molecules Against a Concentration Gradient

• •

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

Many Molecules Enter Cells by Secondary Active Transport

Combines active transport and facilitated diffusion

4

o o

o

Na gradient is produced by the Na pump (active transport) 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 Examples:  Glucose transport across the wall of the gut.  Cotransport and the treatment of cholera.

Cells Regulate Permeability by Adding & Removing Membrane Transport Proteins

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:

Hormone

Transporter

Insulin

GLUT4

Antidiuretic Hormone (ADH)

Aquaporin 2

Permeability Regulation Insulin causes glucose transport molecules to be inserted into muscle and adipose tissue cells. Glucose is then taken up into those tissues, lowering the blood concentration. ADH causes aquaporin 2 proteins to be added to the kidney collecting duct membranes. The result is water conservation. 5

Aldosterone

Na Pump

Aldosterone causes cells in the distal tubules and collecting duct of the kidney to make more Na pump molecules. The final result is that the body retains more Na and secretes more K into the urine.

Endocytosis Can Bring Macromolecules Into the Cell
• • •

In endocytosis the cell membrane bends inward (invaginates), forming a vesicle containing extracellular fluid Can bring in large molecules such as proteins The macromolecules are usually digested by lysosomes

Comparison of Simple Diffusion, Facilitated Transport & Active Transport Property Requires special membrane proteins Highly selective Transport saturates Can be inhibited Hormonal regulation Uphill transport Requires ATP energy Simple Diffusion No No No No No No No Facilitated Active Transport Transport Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes Yes Yes

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 Separation of Charges Causes Voltage Gradients to Develop Across Membranes

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

The Sodium Pump Sets Up Gradients of Na and K Across Cell Membranes

All cells have the Na pump in their membranes o Pumps 3 Nas out and 2 Ks in for each cycle o Requires energy from ATP  Uses about 30% of body's metabolic energy

7

o o o

o o o

This is a form of active transport- can pump ions "uphill", from a low to a high concentration This produces concentration gradients of Na & K across the membrane Typical concentration gradients: In mM/L Out mM/L Gradient orientation Na 10 150 High outside K 140 5 High inside The ion gradients represent stored electrical energy (batteries) that can be tapped to do useful work The Na pump is of ancient origin, probably originally designed to protect cell from osmotic swelling Inhibited by the arrow poisons ouabain and digitalis

Typical Concentration Gradients and Membrane Potentials in Excitable Cells

Notes:
o o o

Concentrations are in millimoles/liter (.15 moles/liter = 150 millimoles/liter) Membrane potential is in millivolts (.07 volts = 70 millivolts) 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.

The Na Pump is Particularly Important in the Kidney and Brain
• • •

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
• • •

Resting cells have more open K channels than other types More K+ passes through membrane than other ions- therefore K+ controls the potential Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells o Raising K will make the membrane potential less negative (depolarization) High blood K+ can cause the heart to stop beating (it goes into permanent contraction)

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. Return to Lecture Note Index / Return to Homepage /Next Lecture . Lecture 39: Regulation of Blood pH Kidneys and Lungs

Blood pH Must be Kept Close to 7.4
• • • •

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 Chemicals Which Stabilize pH

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:

Too Much CO2 or Too Little HCO3 Will Cause Acidosis
• • •

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

Too Much HCO3 or Too Little CO2 Will Cause Alkalosis
• • • •

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

Compensation for alkalosis (rebalances the pH to 7.4): o Remove HCO3 o Add CO2: occurs first because lungs work faster than kidneys

Blood pH is Chiefly Regulated by the Lungs and Kidneys
• •

Normal metabolism produces large amounts of CO2 continuously (about 14 moles/day) If this CO2 were not removed we would rapidly develop fatal 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:
• •

Acid-Base Tutorial, by Alan Grogono of Tulane University, Great illustrations. Acid Base Review, written by David Roth of Temple University. A good concise outline.

Return to Lecture Note Index / Return to Homepage /Next Lecture Lecture 34: Endocrines Control of Ca and Phosphate Over 99% of the Body's Ca is in the Form of Hydroxyapatite: Skeleton and Teeth
• •

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: Mineral Organic & water Notes:

12

Pulp

0%

100%

Dentin

70%

30%

Enamel

97%

3%

Cementum

61%

39%

Bone

65%

35%

Innermost layer of teeth. Contains connective tissue, blood vessels, nerves. Main tooth structure. Middle layer. Similar to bone in structure. Secreted by odontoblasts lining pulp cavity. Hard outer surface of tooth. Secreted by ameloblast cells. Lines the root of the tooth and helps hold the it in the socket. Secreted by the peridontal membrane. Secreted by osteoblasts and broken down by osteoclasts. These processes occur continuously (remodeling).

Bone Has an Organized Structure

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

Osteoblasts and Osteoclasts Make Bone a Dynamic Tissue
• • •

Osteoblast cells build bone Osteoclast cells destroy bone These cells work together to constantly remodel bone

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

Ionized Ca Triggers Secretion and Muscle Contraction
• • • •

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"

Cellular and Serum Ca Levels are Precisely Regulated

Serum Ca is maintained at a few millimoles/liter o Controlled by hormones acting on bone, kidney and intestines o If blood Ca is too low nerves become more excitable, but transmission may be blocked at synapses- the net effect is muscular spasms which can be fatal if they involve respiration Intracellular Ca levels are kept low by active transport: o Keep cytoplasmic Ca at a concentration a thousand times lower than serum Ca (about 0.1 micromoles/liter) o Necessary because high levels of cytoplasmic Ca kill cells- they activate enzymes that destroy proteins and other cell components

Several Major Hormones Regulate Blood Ca

Major Ca regulatory hormones: 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

Parathyroid Hormone Raises Blood 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

Active Vitamin D (Calcitrol) is Made in 3 Steps by Different Organs
• •

Calcitrol and its relatives are steroids derived from cholesterol 3 steps are involved: o The skin uses ultraviolet sunlight to make vitamin D3 (cholecalciferol) from cholesterol o The vitamin D3 is converted to 25-Hydroxycholecalciferol in the liver  Stimulated by PTH o The 25-Hydroxycholecalciferol is made into calcitrol (1, 25Dihydroxycholecalciferol) in the kidney  Stimulated by PTH The main effect of calcitrol is to increase intestinal absorption of Ca

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

Calcitonin Lowers Blood Ca
• • • • •

Calcitonin is made by the C cells of the thyroid gland A large peptide "prohormone" is made and then cut down to the 32 amino acid calcitonin Stimulates osteoblasts, inhibits osteoclasts Causes removal of Ca from serum to calcify new bone Lowers serum Ca (opposes PTH)

In Osteoporosis Bones Decalcify and Fracture

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 An excellent textbook of dental physiology is:

David B. Ferguson, A. Shuttleworth & D.K. Whittaker. Oral Bioscience. Edinburgh: Churchill Livingstone, 1999.

Websites with good information on osteoporosis:
• •

International Osteoporosis Foundation National Osteoporosis Foundation

Return to Lecture Note Index / Return to Homepage /Next Lecture Lecture 37: Kidney Filtration, Secretion, Reabsorption Basic Kidney Anatomy
• •

Kidneys paired, about 150 gm each Urine forming units: o Cortex o Medulla (lobed: renal pyramids) o Cortex and medulla composed chiefly of nephrons and blood vessels o Supplied by renal arteries (branches of descending aorta) and renal veins (branches of inferior vena cava) Urine collecting and expelling units: o Calyces o Renal pelvises o Ureters o Bladder o Urethra

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

• • • •

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
o

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 Nephron is the Fundamental Urine-Producing Unit of the Kidney
• •

• •

We have a total of 2 million nephrons in the 2 kidneys when we are young Components of the nephron (see diagram below): o Glomerulus- tuft of capillaries where filtration occurs o Bowman's capsule- surrounds glomerulus, collects filtrate o Proximal convoluted tubule o Loop of Henle o Distal convoluted tubule o Collecting duct- adjusts volume & concentration of urine Distinctive feature: the tubule makes a sharp bend at the loop of Henle o Because of the bend, tubule fluid moves downward into regions of increasing osmotic pressure (see diagram below) o After the bend the tubule fluid moves upward through regions of decreasing osmotic pressure Glomerulus has large pores, allowing filtration of large volumes of fluid Number of nephrons declines with age, to about 50% at age 60; this causes the GFR to drop to 50% of value in a young person o Loss of nephrons can cause drug overdose in older persons

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 o

Driven by the hydrostatic pressure of the blood (osmosis opposes filtration, but the hydrostatic pressure is larger) Water and small molecules are filtered; blood cells and large molecules (most proteins) do not pass through the filter

Reabsorption & secretion: o As the filtrate passes down the nephron most of it is reabsorbed into the blood Substance Water Na K HCO3 Glucose Urea Inulin % Reabsorbed 99.4% 99.4% 93.3% 100% 100% 53% 0%

Data from: William Ganong. Review of Medical Physiology. 1999.
o o o

A few substances are secreted from the blood to the nephron Reabsorption and secretion are energy intensive- the kidney is one of the most metabolically active organs in the body Filtering substances into the tubules and then reabsorbing nearly 100% of them, using energy, may seem to be a very wastefull process, but it allows the body to

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

Glomerular Filtration is Easy to Measure From Inulin or Creatinine Clearance
• • •

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 o

Filtered only: C = GFR (about 120 mL/min) Filtered + secreted: C will be higher than the GFR

Tubular Reabsorption Has a Maximum Rate
• • •

• •

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

• • •

The kidney can reabsorb glucose at a tubular maximum rate of 320 mg/min 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
o o

The Kidney is an Osmotic Machine

Kidney uses active transport (especially of Na) to set up osmotic gradients o Osmotic gradients are shown in the figure below: osmotic pressure in the cortex is isotonic (~300 milliosmoles/liter) o As you move toward the medulla the osmotic pressure rises, to about 1200 milliosmoles/liter (hypertonic) A distinctive feature of the tubule is the sharp bend at the loop of Henle o Because of the bend, tubule fluid moves downward into regions of increasing osmotic pressure (see diagram below) o After the bend the tubule fluid moves upward through regions of decreasing osmotic pressure

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 Lecture 22: Physiological Adjustment to Exercise Exercise Requires the Coordination of Most of the Body's Organ Systems

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

Force, Work, Energy & Power
• • •

• •

• •

When you push or pull on something you are using force Force causes things to move, produces tension Force depends upon muscle size (proportional to cross sectional area of muscle) o The contactile force is about 3-4 kg/cm2 in both men and women o But men tend to have larger muscles (more cm2) In mechanical processes work = force x distance Work and energy are the same o It is possible to convert one type of energy into another o We store energy in chemicals: carbohydrates = 4 Cal/gm; triglycerides = 9 Cal/gm o Muscles convert chemical energy into mechanical energy Power is the rate of doing work Power is measured in watts. Our bodies at rest run at about 80 watts (the brain is 10 watts-a dim bulb!)

We Store Fuel for Exercise in 3 Different "Tanks"

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 Amount Stored: Amount Stored: 24 Rate of Use (Power)

Fuel

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 Exercise Creates a Demand for Fuel and O2
• •

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

In Exercise Both Tidal Volume and Respiratory Frequency Increase
• • • • •

In heavy exercise respiratory frequency increases from about 15 breathes/min to about 60 breathes/min The tidal volume can increase from about 0.5 L/min to about 2 L/min Note: the maximum possible tidal volume is the vital capacity, but it is too fatiguing to breath in and out for long at the full vital capacity These 2 factors together increase the pulmonary ventilation from about 7.5 L/min to over 100 L/min The stimulus for increased respiration in exercise is not known. o CO2 is a powerful stimulator of respiration, but it does not rise much in exercise o Stimulus may be increased blood K or impulses from muscle proprioceptors Respiration is usually not the limiting factor in endurance exercise

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

Vasoconstriction and Vasodilation are Used to Shift the Circulation
• • • •

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 Rest L/min 1.2 1.0 2.8 5.0 Exercise L/min 0.6 26.0 3.4 30.0

Tissue Viscera Muscle & Heart Other Total

O2 Delivery in the Tissues is Promoted by Acid Conditions (Bohr Effect)

Muscle metabolism produces large amounts of acids: o Under aerobic conditions sugars and fats are burned to CO2, which dissolves to form carbonic acid o Under anaerobic conditions (maximal exercise) lactic acid is formed o Both acids lower the pH Low pH helps the unloading of O2 from hemoglobin; normally only 25% is unloaded, but during exercise as much as 75% may be unloaded (Bohr effect)

26

Increased Blood Flow to the Skin and Sweating Help to Get Rid of Excess Heat
• •

Large amounts of heat are produced in exercise Excess heat must be removed to prevent overheating o As exercise progresses skin blood flow increases to get rid of excess heat o Enormous amounts of heat may be removed by sweating o If the temperature is above body temperature sweating is the only method of heat loss

Summary of Physiological Adjustments to Exercise:

The diagram shows representative values for a well-trained athlete: Lecture 38: Kidney Regulation of Salt and Water

Extracellular Water Must be Closely Regulated to Control Blood Pressure and Edema
• • • • • • •

About 2/3 of the body volume is water Click for a review of body water volumes. Excess water in a body region leads to swelling, which can be harmful or even fatal (i.e., brain swelling) Blood pressure is proportional to the amount of water in the circulatory system If the water volume is low, blood pressure will be too low to push adequate amounts of blood through organs If water volume is high this will cause high blood pressure, which can lead to hemorrhage and strokes Sensory receptors used to monitor the status of salt and water: o Osmoreceptors: respond to changes in osmotic pressure  Found in hypothalamus, kidney, adrenal cortex o Stretch receptors: respond to stretch caused by changes in blood pressure  Found in hypothalamus, carotid sinus, aortic arch, walls of atria

Extracellular Water is Controlled by the Amount of Na in the Extracellular Space

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 Kidney Has an Osmotic Gradient From Cortex to Medulla
• •

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
• • • • •

When a person is dehydrated the blood osmotic pressure rises Under these conditions osmoreceptors in the hypothalamus fire, causing the posterior pituitary to secrete large amounts of ADH The ADH will cause the kidney collecting ducts to insert water pores More water will be conserved, preventing further dehydration The dehydration will also make the person thirsty and drinking will restore the water volume

If ADH is Low the Kidney Makes Large Volumes of Dilute Urine

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

Defects in the ADH Mechanism Cause Diabetes Insipidus
• • •

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)

Summary of Formation of Concentrated and Dilute Urine

Aldosterone Allows the Kidney to Make a Separate Adjustment of the Na Level

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

In Addition to Aldosterone, Renin and Angiotensin are Involved in Na Retention
• •

• • •

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

Summary of the Renin-Angiotensin-Aldosterone Mechanism:

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

Return to Lecture Note Index / Return to Homepage /Next Lecture

Return to Lecture Note Index / Return to Homepage /Next Lecture

32

Lecture: Physiology of Blood I. Components, Characteristics, Functions of Blood A. tissue) a. b. c. erythrocytes - red blood cells leukocytes - white blood cells platelets - cell fragments for clotting Major Components of Blood 1. formed elements - the actual cellular components of blood (special connective

2. blood plasma - complex non-cellular fluid surrounding formed elements; protein & electrolytes B. Separation of Components in a Centrifuge VOLUME 1. 2. 3. clear/yellowish PLASMA thin/whitish buffy coat with LEUKOCYTES & PLATELETS reddish mass - ERYTHROCYTES 55% <1% 45% LAYER top middle bottom

hematocrit - percentage by VOLUME of erythrocytes when blood is centrifuged (normal = 45%) C. Characteristics of Blood 1. 2. 3. 4. 5. 6. 7. 8. D. bright red (oxygenated) dark red/purplish (unoxygenated) much more dense than pure water pH range from 7.35 to 7.45 (slightly alkaline) slightly warmer than body temperature 100.4 F typical volume in adult male 5-6 liters typical volume in adult female 4-5 liters typically 8% of body weight

Major Functions of Blood 1. Distribution & Transport a. oxygen from lungs to body cells

33

b. c. d. e. 2.

carbon dioxide from body cells to lungs nutrients from GI tract to body cells nitrogenous wastes from body cells to kidneys hormones from glands to body cells

Regulation (maintenance of homeostasis) a. maintenance of normal body pH i. blood proteins (albumin) & bicarbonate b. maintenance of circulatory/interstitial fluid i. electrolytes aid blood proteins (albumin) c. maintenance of temperature (blushed skin)

3.

Protection a. b. platelets and proteins "seal" vessel damage protection from foreign material & infections i. leukocytes, antibodies, complement proteins

II.

Erythrocytes (red blood ells; RBCs) A. Structure 1. 2. 3. 3. 5. 6. 7. 7.5 micron diameter; 2.0 micron thick biconcave disk shape; ideal for gas exchange i. spectrin - elastic protein; allows shape change mature cells are anucleate (no nucleus) very few organelles; mainly a hemoglobin carrier i. hemoglobin – 33% of cell mass; carries oxygen no mitochondria; only anaerobic respiration ratio erythrocytes:leukocytes = 800:1 red blood cell count: # cells per cubic millimeter i. normal male count - 5.1 to 5.8 million ii. normal female count - 4.3 to 5.2 million

B.

Functions (oxygen & carbon dioxide transport) 1. hemoglobin - large molecules with globin and hemes

a. globin - complex protein with 4 polypeptides (2 alpha and 2 beta polypeptides) b. heme group - IRON containing pigment part of hemoglobin to which oxygen binds i. each polypeptide has one heme group;each heme carries one O2 c. normal hemoglobin levels (grams/l00 ml blood)

34

2.

i. infants 14-20 grams/l00 ml ii adult female 12-16 grams/100 ml iii adult male 13-18 grams/l00 ml states of hemoglobin

a. oxyhemoglobin - when oxygen is bound to IRON b. deoxyhemoglobin - no oxygen bound to IRON c. carbaminohemoglobin - when carbon dioxide bound (to polypeptide chain) C. Hematopoiesis and Erythropoiesis

1. hematopoiesis (hemopoiesis) - the maturation, development and formation of blood cells a. red bone marrow (myeloid tissue) - location of hematopoiesis; in blood sinusoids which connect with capillaries; mainly in axial skeleton and heads of femur & humerus

hemocytoblast (stem cell) - the mitotic precursor to blood cells before differentiation i. differentiation - maturing cell becomes "committed" to being certain type blood cell 2. erythropoiesis - the maturation, development, and formation of Red Blood Cells (erythrocytes) hemocytoblast -> proerythroblast -> early (basophilic) erythroblast -> late (polychromatophilic) erythroblast -> (hemoglobin) normoblast -> (nucleus ejected when enough hemoglobin) reticulocyte -> (retaining some endoplasmic reticulum) ERYTHROCYTE hemocytoblast -> reticulocyte reticulocyte -> ERYTHROCYTE ERYTHROCYTE lifespan (primarily destroyed by macrophages in the spleen) 3. Regulation of Erythropoiesis a. 3-5 DAYS 2 DAYS (in blood) 100-120 DAYS

b.

hormonal controls - erythropoietin is the hormone that stimulates RBC production DECREASED oxygen level in blood causes KIDNEYS to increase release of erythropoietin

35

1. 2. 3. 4.

Less RBCs from bleeding Less RBCs from excess RBC destruction Low oxygen levels (high altitude, illness) Increased oxygen demand (exercise)

Eythropoietin now genetically engineered and synthesized by AMGEN of Thousand Oaks. Testosterone can also mildly stimulate production of RBCs in humans b. Iron - essential for hemoglobin to carry oxygen 65% of Fe in body is in hemoglobin liver and spleen store most excess Fe bound to ferritin and Fe in blood bound to transferrin daily Fe loss: 0.9 mg men/l.7 mg women women also lose Fe during menstrual flow

i. ii. hemosiderin iii. iv. v.

c. B-complex Vitamins - Vitamin B12 and Folic Acid essential for DNA synthesis in early mitotic divisions leading to erythrocytes D. Erythrocyte Disorders (Anemias & Polycythemias) 1. Anemias - a symptom that results when blood has lower than normal ability to carry oxygen a. Insufficient erythrocyte count i.hemorrhagic anemia - loss of blood from bleeding (wound, ulcer, etc.) ii.hemolytic anemia - erythrocytes rupture (hemoglobin/transfusion problems, infection) iii.aplastic anemia - red marrow problems (cancer treatment, marrow disease, etc.) b. Decrease in Hemoglobin i.iron-deficiency anemia - low Iron levels (diet; absorption, bleeding, etc.) ii.pernicious anemia - low Vitamin B12 (diet, intrinsic factor for Vit B absorption) c. Abnormal Hemoglobin (usually genetic)

36

i. thalassemia - easily ruptured RBCs (Greek & Italian genetic link) ii. 2. sickle-cell anemia - sickle-shaped RBCs (genetic Africa, Asia, southern Europe link)

Polycythemia - excess RBC count, causes thick blood a. b. c. polycythemia vera - bone marrow problem; hematocrit may jump to 80% secondary polycythemia - high altitude (normal); or too much erythropoietin release blood doping in athletes - RBCs previously withdrawn are transfused before an event; more RBCs, more oxygen delivery to the body

III.

Leukocytes (white blood cells; WBCs) A. General Structure and Function 1. 2. 3. 4. 5. 6. 7. 8. protection from microbes, parasites, toxins, cancer 1% of blood volume; 4-11,000 per cubic mm blood diapedesis - can "slip between" capillary wall amoeboid motion - movement through the body chemotaxis - moving in direction of a chemical leukocytosis - increased "white blood cell count" in response to bacterial/viral infection granulocytes - contain membrane-bound granules (neutrophils, eosinophils, basophils) agranulocytes - NO membrane-bound granules (lymphocytes, monocytes)

B.

Granulocytes - granules in cytoplasm can be stained with Wright's Stain; bilobar nuclei; 10-14 micron diameter; all are phagocytic cells (engulf material) 1. neutrophils - destroy and ingest bacteria & fungi (polymorphonuclear leuks.; "polys") a. b. c. d. e. most numerous WBC basophilic (blue) & acidophilic (red) defensins - antibiotic-like proteins (granules) polymorphonuclear - many-lobed nuclei causes lysis of infecting bacteria/fungi

37

f. 2.

HIGH poly count --> likely infection

eosinophils - lead attack against parasitic worms a. only 1-4% of all leukocytes b. two-lobed, purplish nucleus c. acidophilic (red) granules with digest enzymes d. phagocytose antigens & antigen/antibody complex e. inactivate chemicals released during allergies 3. a. b. c. d. e. f. basophils - releases Histamine which causes inflammation, vasodilation, attraction of WBCs RAREST of all leukocytes (0.5%) deep purple U or S shaped nucleus basophilic (blue) granules with HISTAMINE related to "mast cells" of connective tissue BOTH release Histamine with "IgE" signal antihistamine - blocks the action of Histamine in response to infection or allergic antigen

C.

Agranulocytes - WBCs without granules in cytoplasm 1. lymphocytes - two types of lymphocytes a. T lymphocytes - (thymus) respond against virus infected cells and tumor cells b. B lymphocytes - (bone) differentiate into different "plasma cells" which each produce antibodies against different antigens c. lymphocytes primarily in lymphoid tissues d. very large basophilic (purple) nucleus e. small lymphocytes in blood (5-8 microns) f. larger lymphocytes in lymph organs (10-17 mic) 2. a. b. monocytes - differentiate to become macrophages; serious appetites for infectious microbes largest of all leukocytes (18 microns) dark purple, kidney shaped nucleus

D.

Leukopoiesis and Colony Stimulating Factors (CSFs) 1. 2. leukopoiesis - the production, differentiation, and development of white blood cells colony stimulating factors (CSF) - hematopoietic hormones that promote leukopoiesis

38

a.

produced by Macrophages and T lymphocytes i. ii. iii. iv. v. macrophage-monocyte CSF (M-CSF) granulocyte CSF (G-CSF) granulocyte-macrophage CSF (GM-CSF) multi CSF (multiple lymphocyte action) interleukin 3 (IL-3) (general lymphocytes)

3. 1.

leukopoiesis - all cells derived from hemocytoblast monoblast-> promonocyte-> MONOCYTE-> (macrophages) (3 month lifespan) 2. lymphocyte stem cell-> lymphoblast-> prolymphocyte-> LYMPHOCYTE-> (B cell  plasma cell, memory cells, (days-decades lifespan)

myeloid stem cell-> myeloblast-> promyelocyte-> a. myelocyte-> b. metamyelocyte-> T-cells) c. band cell-> EOSINOPHIL NEUTROPHIL BASOPHIL E.

} } (0.5 to 9 day lifespan) }

Disorders of Leukocytes 1. 2. leukopenia - abnormally low WBC count a. HIV infection, glucocorticoids, chemotherapy leukemia - cancerous condition of "line" of WBCs a. b. c. d. e. f. g. 3. myelocytic leukemia (myelocytes) lymphocytic leukemia (lymphocytes) acute leukemia - cancer spreads rapidly chronic leukemia - cancer progresses slowly anemia, fever, weight loss, bone pain death from internal hemorrhage or infection chemotherapy & radiation therapy used to treat

infectious mononucleosis - caused by Epstein-Barr virus, excessive monocytes and lymphocytes; fatigue, sore throat, fever; 3 week course

IV.

Platelets (thrombocytes - "clotting") A. General Characteristics 39

1. 2. 3. 4. B.

very small, 2-4 microns in diameter approximately 250-500,000 per cubic millimeter essential for clotting of damaged vasculature thrombopoietin - regulates platelet production

Formation of Platelets hemocytoblast-> myeloid stem cell-> megakaryoblast-> promegakaryocyte-> megakaryocyte-> (large multilobed nucleus) platelets (anucleated parts of megakaryocyte cytoplasm)

V.

Plasma (the liquid part of blood) A. General Characteristics 1. 2. 3. plasma makes up 55% of normal blood by volume water is 90% of the plasma by volume many different SOLUTES in the plasma a. b. c. d. e. f. albumin - pH buffer & osmotic pressure globulins - binding proteins & antibodies clotting proteins - prothrombin & fibrinogen other proteins - enzymes, hormones, others nutrients - glucose, fatty acids, amino acids, cholesterol, vitamins electrolytes - Na+, K+, Ca++, Mg++, Cl-, phosphate, sulfate, bicarbonate, others

VI.

Hemostasis (stoppage of blood flow after damage) A. General Characteristics 1. 2. 3. B. by: vascular spasms (vasoconstriction at injured site) platelet plug formation (plugging the hole) coagulation (blood clotting - complex mechanism)

Vascular Spasms 1. first response to vascular injury - VASOCONSTRICTION is stimulated

40

a. b. c. C.

compression of vessel by escaping blood injury "chemicals" released by injured cells reflexes from adjacent pain receptors

Formation of a Platelet Plug 1. 2. 3. 4. 5. 6. 7. damage to endothelium of vessel platelets become spiky and sticky in response platelets attach to damaged vessel wall to plug it platelets produce thromboxane A2 - granule release serotonin release enhances vascular spasm ADP - attracts and stimulates platelets at site prostacylin - inhibits aggregation at other sites

VII.

Coagulation (blood clotting) A. General Events in Clotting platelet cells activated by damage-> PF3 and/or Tissue Factor produced by platelet cells-> Factor X activated-> prothrombin activator (enzyme) produced-> prothrombin conversion -> thrombin (another enzyme) thrombin stimulates: fibrinogen----> fibrin mesh 1. anticoagulant - chemical that inhibits clotting 2. procoagulant - chemical that promotes clotting 3. intrinsic pathway - within the damaged vessel a. more procoagulants needed (I-XIII) toward PF3 and Factor X b. allows more "scrutiny" before clotting occurs 4. extrinsic pathway - in outer tissues around vessel

a. tissue thromboplastin (Tissue Factor) - skips intrinsic steps straight to PF3 and Fac X b. allows rapid response to bleeding out of vessel (clot can form in 10 to 15 seconds) 5. After activation of Factor X, common pathway: Factor X, PF3 (thromboplastin), Factor V, Ca++ --> prothrombin activator -> prothrombin converted -> thrombin (active enzyme) thrombin stimulates: fibrinogen -> fibrin (meshwork)

41

Ca++ & thrombin -> Factor XIII (fibrin stabilizer) B. Clot Retraction (shrinking of clot) 1. 2. 3. C. actomyosin - causes contraction of platelets blood serum - plasma WITHOUT clotting Factors platelet-derived growth factor (PDGF) - stimulates fibroblast migration and endothelial growth

Clot Eradication (Fibrinolysis) 1. 2. 3. 4. healing occurs over 2 - 10 days tissue plasminogen activator (TPA) - causes the activation of plasminogen plasminogen--> plasmin plasmin degrades proteins within the clot

D.

Factors Limiting Growth and Formation of Clots 1. Limiting Normal Clot Growth a. b. blood moves too fast to allow procoagulants factors interfere with normal clotting i. ii. iii. prothrombin III - deactivates thrombin protein C - inhibits clotting Factors heparin - inhibits thrombin; prevents adherence of platelets to injured site

VII.

Disorders of Hemostasis A. Thromboembolytic Disorders (undesirable clotting) 1. 2. thrombus - blood clot in normal blood vessel embolus -blood clot/gas bubble floating in blood a. TPA, streptokinase - can dissolve a clot b. aspirin - inhibits Thromboxane formation c. heparin - inhibits thrombin & platelet deposit d. dicumarol - anticoagulant, blocks Vitamin K

B.

Bleeding Disorders 1. thrombocytopenia - reduced platelet count; generally below 50,000 per cubic millimeter; can cause excessive bleeding from vascular injury

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 hemophilias - hereditary bleeding disorders that occur almost exclusively a. b. c. hemophilia A - defective Factor VIII (83%) hemophilia B - defective Factor IX (10%) Genentech. Inc. - now produces genetically engineered TPA and Factor VIII; patients do not need transfusions as often

3. in males

VIII.

Blood Transfusions and Blood Typing 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 B. Human Blood Groups 1. 2. TYPE type A type B type AB type O agglutinogens - glycoproteins on the surface of blood cells; causes "agglutination" (clumping) ABO Blood Groups - determined by presence or absence of Type A and Type B agglutinogen proteins on cell membrane PEOPLE (30-40%) (l0-30%) (3-5%) (40-50%) Antibodies Anti-B Anti-A none Anti-A, Anti-B Receive Blood from: A, O B,O A, B, AB, O O only

GENES A/A, A/O, O/A B/B, B/O, O/B A/B or B/A no A or B 3.

agglutinins - antibodies against either A or B agglutinogen (whichever is not present) a. transfusion reaction - patient's antibodies attack the donor blood i. ii. iii. iv. b. A (anti-B) receives A,O (not B) B (anti-A) receives B,O (not A) AB (none) receives A, B, AB, O universal recipient O (anti-A,anti-B) receives O universal donor

agglutination - when incorrect blood transfused, antibodies will "clump" new blood

43

c.

hemolysis - after clumping, RBCs may rupture, releasing hemoglobin, harming kidney i. dilute hemoglobin, administer diuretics

4.

Rh factor - a different group of agglutinogens a. b. c. Rh positive (Rh+) - an Rh factor is present Rh negative (Rh-) - NO Rh factor transfusion reaction - delayed and less severe than in ABO confrontation d. erythroblastosis fetalis - Rh- mother antibodies attack Rh+ of older newborn; results in anemia and low oxygen levels (hypoxia) i. RhoGAM - serum with anti-Rh agglutinins which will clump the Rh factor, blocking the reaction of mothers antibodies ii. exchange transfusion - directly from the mother (Rh-) to the newborn (Rh+) 5. Blood Typing - mixing Donors Blood with Recipient Antibodies (Anti-A, Anti-B, anti-Rh) in order to identify agglutination

6.

Expanding Blood Volume to Avoid Shock a. b. c. pure plasma without antibodies plasma expanders - purified human serum albumin, plasminate, dextran isotonic saline - normal electrolyte solution isotonic to blood plasma (Ringer's Solution)

7.

Diagnostic Blood Tests a. b c. d. e. f.

anemia - low hematocrit (below 35%) lipidemia - high in fat; yellowish plasma diabetes - blood glucose level infection - generally higher WBC count leukemia - significantly higher WBC count differential WBC count - counts % of each of the different leukocytes (helps diagnose) g. prothrombin time - time for clotting to occur h. platelet count - diagnose thrombocytopenia i. complete blood count - overall blood review Lecture Notes: Immune System (Part I: Innate Immune System) I. Parts of the Immune System A. Innate or Nonspecific system 1. External body membranes like skin and mucosae

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 II. Innate defenses A. Function 1. combat pathogens which are harmful or disease-causing microorganisms 2. in a state of readiness and responds to protect the body from ALL foreign substances starting within minutes of invasion. B. Surface Barriers 1. Skin i. heavily keratinized epithelial membrane is a physical barrier ii. resistant to most weak acids, weak bases, bacterial enzymes and toxins. iii. secretions are acidic (pH 3-5) and inhibit bacterial growth iv. sebum contains chemicals that are toxic to bacteria 2. Mucous membranes i. line all body cavities that open to the exterior including the digestive, respiratory, urinary, and reproductive tracts. ii. stomach secretes HCl and protein-digesting enzymes which kill microorganisms. iii. Saliva and lacrimal fluid contains lysozyme, an enzyme that destroys bacteria. iv. Sticky mucus traps microorganism that enter the digestive and respiratory passageways. v. structure modifications such as the tiny mucus-coated hairs and ciliated mucosa of the respiratory tract which trap and sweep particles away from lower respiratory passages. 3. When surface barriers are breached by small nicks or cuts then the microorganisms invade deeper tissues and the internal innate defenses are important 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 I. Cardiac Muscle (compare to Skeletal Muscle) Cardiac Muscle Cells 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 Skeletal Muscle Cells 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. Na+ influx from extracellular space, causes positive feedback opening of voltage-gated Na+ channels; membrane potential quickly depolarizes (-90 to +30 mV); Na+ channels close within 3 ms of opening. Depolarization causes release of Ca++ from sarcoplasmic reticulum (as in skeletal muscle), allowing sliding actin and myosin to proceed. Depolarization ALSO causes opening of slow Ca++ channels on the membrane (special to cardiac muscle), further increasing Ca++ influx and activation of filaments. This causes more prolonged depolarization than in skeletal muscle, resulting in a plateau action potential, rather than a "spiked" action potential (as in skeletal muscle cells).

2. 3.

Differences Between Skeletal & Cardiac MUSCLE Contraction 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. Automicity (Autorhythmicity) - some cardiac muscle cells are "self-excitable" allowing for rhythmic waves of contraction to adjacent cells throughout the heart. Skeletal muscle cells must be stimulated by independent motor neurons as part of a motor unit. Length of Absolute Refractory Period - The absolute refractory period of cardiac muscle cells is much longer than skeletal muscle cells (250 ms vs. 2-3 ms), preventing wave summation and tetanic contractions which would cause the heart to stop pumping rhythmically. Internal Conduction (Stimulation) System of the Heart A. General Properties of Conduction 1. 2. 3. heart can beat rhythmically without nervous input nodal system (cardiac conduction system) - special autorhythmic cells of heart that initiate impulses for wave-like contraction of entire heart (no nervous stimulation needed for these) gap junctions - electrically couple all cardiac muscle cells so that depolarization sweeps across heart in sequential fashion from atria to ventricles

2.

3.

III.

B.

"Pacemaker" Features of Autorhythmic Cells

1.

pacemaker potentials - "autorhythmic cells" of heart muscle create action potentials in rhythmic fashion; this is due to unstable resting potentials which slowly drift back toward threshold voltage after repolarization from a previous cycle.

Theoretical Mechanism of Pacemaker Potential: a. b. c. K+ leak channels allow K+ OUT of the cell more slowly than in skeletal muscle Na+ slowly leaks into cell, causing membrane potential to slowly drift up to the threshold to trigger Ca++ influx from outside (-40 mV) 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 when peak depolarization is achieved, voltage-gated K+ channels open, causing repolarization to the "unstable resting potential" cycle begins again at step a. C. Anatomical Sequence of Excitation of the Heart 1. Autorhythmic Cell Location & Order of Impulses (right atrium) (right AV valve) sinoatrial node (SA) -> atrioventricular node (AV) -> atrioventricular bundle (bundle of His) -> right & left bundle of His branches -> Purkinje fibers of ventricular walls

d. e.

(from SA through complete heart contraction = 220 ms = 0.22 s) a. sinoatrial node (SA node) "the pacemaker" - has the fastest autorhythmic rate (7080 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 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) atrioventricular bundle (bundle of His) - in the interATRIAL septum (connects L and R atria)

b.

c.

d. e.

L and R bundle of His branches - within the interVENTRICULAR septum (between L and R ventricles) 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

D. Special Considerations of Wave of Excitation 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. initial SA node excitation causes contraction of both the R and L atria contraction of R and L ventricles begins at APEX of heart (inferior point), ejecting blood superiorly to aorta and pulmonary artery the bundle of His is the ONLY link between atrial contraction and ventricular contraction; AV node and bundle must work for ventricular contractions since cells in the SA node has the fastest autorhythmic rate (70-80 per minute), it drives all other autorhythmic centers in a normal heart arrhythmias - uncoordinated heart contractions fibrillation - rapid and irregular contractions of the heart chambers; reduces efficiency of heart defibrillation - application of electric shock to heart in attempt to retain normal SA node rate ectopic focus - autorhythmic cells other than SA node take over heart rhythm nodal rhythm - when AV node takes over pacemaker function (40-60 per minute) extrasystole - when outside influence (such as drugs) leads to premature contraction heart block - when AV node or bundle of His is not transmitting sinus rhythm to ventricles

E.

External Innervation Regulating Heart Function 1. 2. heart can beat without external innervation external innervation is from AUTONOMIC SYSTEM

parasympathetic - (acetylcholine) DECREASES rate of contractions cardioinhibitory center (medulla) -> vagus nerve (cranial X) -> heart sympathetic - (norepinephrine) INCREASES rate of contractions cardioacceleratory center (medulla) -> lateral horn of spinal cord to preganglionics Tl-T5 -> postganlionics cervical/thoracic ganglia ->

heart IV. Electrocardiography: Electrical Activity of the Heart A. Deflection Waves of ECG 1. P wave - initial wave, demonstrates the depolarization from SA Node through both ATRIA; the ATRIA contract about 0.1 s after start of P Wave QRS complex - next series of deflections, demonstrates the depolarization of AV node through both ventricles; the ventricles contract throughout the period of the QRS complex, with a short delay after the end of atrial contraction; repolarization of atria also obscured T Wave - repolarization of the ventricles (0.16 s) PR (PQ) Interval - time period from beginning of atrial contraction to beginning of ventricular contraction (0.16 s) QT Interval the time of ventricular contraction (about 0.36 s); from beginning of ventricular depolarization to end of repolarization

2.

3. 4. 5. V.

The Normal Cardiac Cycle A. General Concepts 1. 2. 3. B. systole - period of chamber contraction diastole - period of chamber relaxation cardiac cycle - all events of systole and diastole during one heart flow cycle

Events of Cardiac Cycle 1. * * * * * * * 2. mid-to-late ventricular diastole: ventricles filled the AV valves are open pressure: LOW in chambers; HIGH in aorta/pulmonary trunk aortic/pulmonary semilunar valves CLOSED blood flows from vena cavas/pulmonary vein INTO atria blood flows through AV valves INTO ventricles (70%) atrial systole propels more blood > ventricles (30%) atrial diastole returns through end of cycle ventricular systole: blood ejected from heart

* * * * * 3. * * *

filled ventricles begin to contract, AV valves CLOSE isovolumetric contraction phase - ventricles CLOSED contraction of closed ventricles increases pressure ventricular ejection phase - blood forced out semilunar valves open, blood -> aorta & pulmonary trunk isovolumetric relaxation: early ventricular diastole ventricles relax, ventricular pressure becomes LOW semilunar valves close, aorta & pulmonary trunk backflow dicrotic notch - brief increase in aortic pressure

TOTAL CARDIAC CYCLE TIME (normal 70 beats/minute) atrial systole (contraction) ventricular systole (contraction) quiescent period (relaxation) VI. Heart Sounds: Stethoscope Listening A. Overview of Heart Sounds

= = = =

0.8 second 0.1 second 0.3 second 0.4 second

B.

1. lub-dub, - , lub, dub, 2. lub - closure of AV valves, onset of ventricular systole 3. dub - closure of semilunar valves, onset of diastole 4. pause - quiescent period of cardiac cycle 5. tricuspid valve (lub) - RT 5th intercostal, medial 6. mitral valve (lub) - LT 5th intercostal, lateral 7. aortic semilunar valve (dub) - RT 2nd intercostal 8. pulmonary semilunar valve (dub) - LT 2nd intercostal Heart Murmurs 1. 2. 3. murmur - sounds other than the typical "lub-dub"; typically caused by disruptions in flow incompetent valve - swishing sound just AFTER the normal "lub" or "dub"; valve does not completely close, some regurgitation of blood stenotic valve - high pitched swishing sound when blood should be flowing through valve; narrowing of outlet in the open state

VII.

Cardiac Output - Blood Pumping of the Heart A. General Variables of Cardiac Output

1. 2. 3.

Cardiac Output (CO) - blood amount pumped per minute Stroke Volume (SV) - ventricle blood pumped per beat Heart Rate (HR) - cardiac cycles per minute HR (beats/min) X SV (ml/beat) 5.25 L/min

CO (ml/min) = normal CO = B.

75 beats/min X 70 ml/beat =

Regulation of Stroke Volume (SV) 1. 2. end diastolic volume (EDV) - total blood collected in ventricle at end of diastole; determined by length of diastole and venous pressure (~ 120 ml) end systolic volume (ESV) - blood left over in ventricle at end of contraction (not pumped out); determined by force of ventricle contraction and arterial blood pressure (~50 ml) EDV (ml/beat) 120 m1/beat ESV (ml/beat) 50 ml/beat = 70 ml/beat

SV (ml/beat) = normal SV = 3.

Frank-Starling Law of the Heart - critical factor for stroke volume is "degree of stretch of cardiac muscle cells"; more stretch = more contraction force a. increased EDV = more contraction force i. ii. slow heart rate = more time to fill exercise = more venous blood return

C.

Regulation of Heart Rate (Autonomic, Chemical, Other) 1. Autonomic Regulation of Heart Rate (HR) a. b. c. d. sympathetic - NOREPINEPHRINE (NE) increases heart rate (maintains stroke volume which leads to increased Cardiac Output) parasympathetic - ACETYLCHOLINE (ACh) decreases heart rate vagal tone - parasympathetic inhibition of inherent rate of SA node, allowing normal HR baroreceptors, pressoreceptors - monitor changes in blood pressure and allow reflex activity with the autonomic nervous system

2.

Hormonal and Chemical Regulation of Heart Rate (HR)

a. b. c. * * * * * 3.

epinephrine - hormone released by adrenal medulla during stress; increases heart rate thyroxine - hormone released by thyroid; increases heart rate in large quantities; amplifies effect of epinephrine Ca++, K+, and Na+ levels very important; hyperkalemia - increased K+ level; KCl used to stop heart on lethal injection hypokalemia - lower K+ levels; leads to abnormal heart rate rhythms hypocalcemia - depresses heart function hypercalcemia - increases contraction phase hypernatremia - HIGH Na+ concentration; can block Na+ transport & muscle contraction

Other Factors Effecting Heart Rate (HR) a. normal heart rate fetus 140 - 160 beats/minute female 72 - 80 beats/minute male 64 - 72 beats/minute

b. c. d. e. f.

exercise - lowers resting heart rate (40-60) heat - increases heart rate significantly cold - decreases heart rate significantly tachycardia - HIGHER than normal resting heart rate (over 100); may lead to fibrillation bradycardia - LOWER than normal resting heart rate (below 60); parasympathetic drug side effects; physical conditioning; sign of pathology in non-healthy patient

VIII. Imbalance of Cardiac Output & Heart Pathologies A. Imbalance of Cardiac Output 1. congestive heart failure - heart cannot pump sufficiently to meet needs of the body a. b. c. coronary atherosclerosis - leads to gradual occlusion of heart vessels, reducing oxygen nutrient supply to cardiac muscle cells; (fat & salt diet, smoking, stress) high blood pressure - when aortic pressure gets too large, left ventricle cannot pump properly, increasing ESV, and lowering SV myocardial infarct (MI) - "heart cell death" due to numerous factors, including coronary artery occlusion

d. e.

pulmonary congestion - failure of LEFT heart; leads to buildup of blood in the lungs peripheral congestion - failure of RIGHT heart; pools in body, leading to edema (fluid buildup in areas such as feet, ankles, fingers)

B.

Heart Pathologies (Diseases of the Heart) 1. congenital heart defects - heart problems that are present at the time of birth a. 2. 3. 4. patent ductus arteriosus - bypass hole between pulmonary trunk and aorta does not close

sclerosis of AV valves - fatty deposits on valves; particularly the mitral valve of LEFT side; leads to heart murmur decline in cardiac reserve - heart efficiency decreases with age fibrosis and conduction problems - nodes and conduction fibers become scarred over time; may lead to arrhythmias Lecture: Renal Physiology

I.

Overview of Nephron Structure and Function
A. General Nephron Structure 1. 2. 3. 4. 5. 6. B. glomerulus - site of filtration from arterial blood proximal convolute tubule- first tube off glomer. Loop of Henle - U-turn connecting tubules distal convoluted tubule - to the Collecting Tubule collecting tubule - urine from many nephron peritubular capillaries - "around" the "tubes"

General Nephron Function 1. 2. 3. glomerular filtration tubular reabsorption tubular secretion

C.

Fluid Processing in the Kidneys 180 liters of blood fluid processes each day 1.5 liters of urine produced each day

II.

Glomerular Filtration
A. Filtration Membrane

1. 2.

hydrostatic pressure - forces 1/5 of blood fluid through capillary' walls into glomerular capsule 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 solutes that can pass into glomerular capsule < 3 nm easily pass (water, sugar, amino acids, nitrogenous waste molecules) > 9 nm larger proteins cannot pass through

3.

B.

Net Filtration Pressure NFP = force OUT of blood - force to remain IN blood NFP = glomerular (glomerular + capsular ) hydrostatic osmotic hydrostatic pressure pressure pressure NFP = 55 mm Hg ( 30 mm Hg + l5mmHg) NFP = 55 mm Hg (45 mm Hg) NFP = net filtration pressure = 10 mm Hg [This is the NET forces pushing fluid/solutes OUT of blood] 1. glomerular filtration rate = milliliters of blood fluid filtered by glomerulus each minute

Factors effecting the GFR: a. total filtration surface area b. membrane permeability to fluid/solutes c. Net Filtration Pressure 2. 3. Normal GFR = 125 ml/min (7.5 L/hr, 180 L/day) NFP - primary factor controlling GFR a. bleeding - NFP drops, lowers the pressure b. dehydration - NFP drops, lowers the pressure

D.

Intrinsic Controls: Regulation of Glomerular Filtration 1. 2. renal autoregulation - rate of FILTRATE production must be coordinated with reabsorption rate myogenic mechanism - circular muscle around the glomerular arterioles reacts to pressure changes a. increased blood pressure -> vasoconstriction b. decreased blood pressure -> vasodilation tubuloglomerular feedback mechanism - macula densa cells (of juxtaglomerular apparatus) sense the solute concentration of the FILTRATE a. b. 4. low concentration > vasodilation high concentration -> vasoconstriction

3.

renin-angiotensin mechanism

renin (released by juxtoglomerular cells) -> angiotensinogen -> angiotensin I -> angiotensin II -> global vasoconstrictor (rise in blood pressure) release of aldosterone (resorption of more Na+)

Factors causing release of Renin: a. b. c. E. reduced stretch of juxtaglomerular cells stimulation by macula densa cells (as above) stimulation of juxtaglomerular cells by sympathetics

Extrinsic Controls: Sympathetic Innervation 1 2 sympathetics - cause increased release of renin epinephrine - causes increased vasoconstriction

III.

Tubular Reabsorption: Reabsorbing the Glomerular Filtrate
A. Overview of Reabsorption 1. 2. 3. filtrate - all fluid and its solutes pushed into the capsule urine - filtrate minus reabsorbed substances + secreted substances route of reabsorption (transepithelial process)

luminal surface of tubule cells >> basolateral membrane of tubule cells >> interstitial fluid between tubule cells and capillaries >> endothelium of the peritubular capillary 4. 5. B. most sugars and amino acids are reabsorbed water and ion reabsorption depends on hormonal control

Active Tubular Reabsorption 1. glucose, amino acids, lactate, vitamins, ions a. b. c. 2. move across luminal surface by diffusion actively transported across basolateral membrane i. cotransported with Na+ diffuse into capillary by diffusion

transport maximum (Tm) when "carrier proteins" for specific solute becomes saturated and cannot carry the substance across the membrane a. diabetes mellitus - lower Tm (glucose lost)

C.

Passive Tubular Resorption 1. 2. 3. 4. Na+ driven into interstitial space actively (above) HCO3- and Cl- follow Na+ into the space obligatory water resorption - water follows ions into the interstitial space between tubule & capillary solvent drags - solutes will begin to move into tubule from filtrate, following water (especially some urea and lipid-soluble molecules)

D.

Nonreabsorbed Substances

1.

urea, creatinine, uric acid - most is not reabsorbed because of the following reasons a. b. c. no carrier molecules for active transport not lipid-soluble too large (as with most proteins)

E.

Absorption in Different Regions of Renal Tubule 1. proximal tubule - closest to the glomerular capsule a. b. c. 2. almost all glucose & amino acids 75-80% of water and Na+ most active transport of ions

Loop of Henle - connects proximal & distal tubules Regulates Total water retained or lost: a. descending limb - water can return to blood vessels b. ascending limb – water impermeable but releases ions to the interstitial space increasing osmotic pressure so that water can be reabsorbed from other parts of the renal tubule

3.

distal tubule & collecting duct - final passageway a. b. antidiuretic hormone (ADH) - causes increased permeability to Na+ and water, allow resorption aldosterone - stimulated by renin-angiotensin, enhances Na+ resorption (water follows). Triggered by i. lower blood pressure ii. low Na+ concentration (hyponatremia)

c.

atrial natriuretic factor (ANF) - reduces Na+ permeability, less water (in response to high B.P.)

IV.

Tubular Secretion
A. Movement from Capillaries to Tubular Cells 1. 2. K+, creatinine, ammonia, organic acids, drugs Primary functions of tubular secretion: a. b. c. d. moving drugs into the urine moving more urea & uric acid into urine removing excess K+ from blood regulating pH (H+ ion removal)

V.

Regulation of Urine Concentration & Volume
A. Osmolarity - Number of Solute particles in 1 Liter water 1. 2. independent of size of solute (Na +, glucose) 1 osmol = 6.02 X l023 particle in I Liter

3. 4. B.

milliosmol (mosm) = 0.001 osmol normal body fluids = 300 mosm

Countercurrent Multiplier Mechanism for Maintenance of Blood/Urine Osmolarity 1. 2. Water moves out along Descending Limb of the Loop of Henle, creating 1200 mosm urine at the base 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. In times of dehydration, Collecting Tubules leak urea to interstitial space, further increasing water retention by increasing osmolarity. Vasa recta (capillaries around Loop of Henle) have no Net Effect on water/salt balance

3. 4.

C.

Formation of Dilute Urine 1. 2. 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 Urine may be as low as 50 mosm

D.

Formation of Concentrated Urine (Water Conservation) 1. antidiuretic hormone (ADH) - stimulates resorption of water in the Distal and Collecting Tubules

E.

Diuretics (Stimulate Water Loss) 1. 2. 3. alcohol inhibits action of ADH caffeine - causes renal vasodilation; increases GFR Na+ resorption blockers - block Na+ movement

VI.

Renal Clearance
A. Renal Clearance (RC) - the rate at which the kidney can remove a substance from the blood RC = U/P X V

U/P
V B.

=
=

concentration of substance in urine (mg/ml) concentration of substance in plasma (mg/ml)
rate of the formation of urine (ml/minute) (normal = 1 ml/minute)

Glomerular Filtration Rate = 125 ml/minute; (determined by challenge with "Inulin") 1. 2. RC < 125 - reabsorption is occurring RC > 125 - tubule cells secrete into the urine

VII.

Characteristics and Composition of Urine

A.

Physical Characteristics 1. 2. 3. 4. color - clear to yellowish; influenced by diet, drugs, and health state odor - slightly aromatic; influenced by diet, drugs, and health state pH (H+ conc.) - usually about 6; changes in diet can effect the pH specific gravity - compared density to distilled water; urine slightly heavier (with solute s)

B.

Chemical Composition 1. 2. 95% water 5% solutes - urea (breakdown of amino acids); uric acid; creatinine

Lecture: Physiology of Vision I. Overview of Light and Optics A. Wavelength and Colors of Visible Radiation 1. electromagnetic radiation

gamma rays

X-rays UV light VISIBLE LIGHT Infrared Radio Wave medium (380-750 nm) long (102 nm)

short (10-5 nm)

2. wave-photon duality - light travels in wave-like fashion with "single packets" of energy called photons 3. visible spectrum - different colors of light have different wavelengths

Violet 380nm

Blue 480nm

Green 550nm

Yellow 630nm

Orange 680nm

Red 730nm

4. color of an object - the color of an object is determined by which wavelengths are REFLECTED back to the retina (not absorbed by the object) a. b. white - all wavelengths reflected by object black - all wavelengths absorbed by object

B.

Refraction of Light and Convex Lenses 1. light refraction - light will bend when it passes from one medium (air) into another (lens) e.g. pencil in glass of water 2. convex lens - (thicker at center, tapered at edge) causes light to bend so that it comes together at a focal point a. real image - image at focal point of convex lens ---> inverted & reversed 3. focusing light on the retina a. b. 4. cornea - constant (unchanging) refraction lens - can change refraction and focal length; ciliary muscles change convexity of the lens

Focusing for Distance Vision a. b. far point of vision - distance beyond which lens will not change its shape (about 20 feet) (flattest point of the lens) emmetropic eye - normal, healthy eye

5.

Focusing for Close Vision

Less than 6 feet, several adjustments are made: a. accommodation of lens - lens shape becomes more convex, light rays bend more sharply, shorter focal length for the closer object (ciliary muscles for lens) i. near point of vision - shortest distance for focusing (maximum convexity of lens); about 8-10 inches; gets worse with age ii. presbyopia - poor close vision in elderly; inelasticity of the lens b. c. C. accommodation of pupils - constriction of pupils; better focus, less divergent rays (constrictor muscles of iris) convergence of eyes - eyes rotate medially to keep image on center of the retina (medial rectus muscles of eyeballs)

Vision Problems Related to Refraction

1.

myopia ("nearsighted") - distant objects are blurred; distant objects are focused in front of the retina, rather than directly on it a. b. eyeball too long; lens too strong concave lens can correct light before eye

2.

hyperopia ("farsightedness") - close objects are blurred; close objects are focused beyond the retina, rather than directly on it a. b. eyeball too short; poor refraction of a lens convex lens can correct light before eye

3.

astigmatism - blurry images at all distances; unequal curves on lens and/or cornea, creating discontinuous image on the retina

II.

Anatomy, Biochemistry, & Physiology of Photoreceptors A. Functional Anatomy of Photoreceptors

1. General Structure of Rods and Cones "pigmented base" of retina outer segment (pigmented discs) connecting stalk inner segment (mitochondria) outer fiber cell body (nucleus) inner fiber synaptic ending bipolar cell ganglion cell (axons carried to brain by optic nerve) a. outer segment - contain membrane-bound discs with pigments that absorb and react to light i. rods - pigment discs stacked like pennies all the way to the base, membranes are DISTINCT from the plasma membrane 1. 2. 3. 4. 5. sensitive to dim light (night vision) respond to ALL wavelengths (colors) only "grey" information to the brain 100 rods per ganglion cell to brain widely spread throughout the retina

"neural layer"

6. not good for visual acuity ii. cones - pigment discs taper off toward the base, membranes are CONTINUOUS with the plasma membrane 1. require bright light for stimulation 2. different cones have different pigments specific for certain wavelengths (colors) 3. can convey color information to brain 4. 1-3 cones per ganglion cell to brain 5. primarily concentrated in fovea (center) 6. essential for visual acuity B. Biochemistry of Visual Pigments 1. 2. opsin - transmembrane protein in the membrane of pigmented discs of rods and cones retinal - light absorbing molecule that changes shape when struck by a photon of light a. b. c. C. vitamin A - precursor to retinal (eat your carrots!!!!!!) 11-cis isomer of retinal - non-activated form of retinal, prior to absorption of photon energy; has a "kinked" double bond all trans isomer of retinal - activated form of retinal, after struck by photon of light; double bond straightens out

Excitation of Rods 1. 2. rhodopsin - visual pigment in rods; in membranes of pigmented discs of outer segment bleaching of pigment - breakdown of rhodopsin after the absorption of light rhodopsin  light all-trans retinal + scotopsin

11-cis retinal  + scotopsin 3.

all-trans retinal - causes HYPERPOLARIZATION of rod a. b. c. d. Na+ channels (open in dark) are closed rod is hyperpolarized (increased negativity) Ca++ channels in synapse close less neurotransmitter released by the rod

D.

Excitation of Cones

1. photopsins - 3 distinct pigments in cones are sensitive to 3 different parts of visible spectrum a. b. c. blue cones - maximum sensitivity at 455 nm green cones - maximum sensitivity at 530 nm red cones - maximum sensitivity at 625 nm

2. different colors - differential activation of each of the three different cones 3. color blindness inherit gene for one of the photon proteins that is deficient (mainly male), most common are red and green mutations E. Light and Dark Adaptation of Rhodopsin 1. light adaptation - very dark  very bright a. b. c. d. e. rhodopsin in rods is quickly bleached out sensitivity to shallow light disappears rods are inhibited by other retinal cells cones are activated to take over (5 mins.) consensual pupil reflex - constriction

2. dark adaptation - very bright  very dark a. b. c. d. cones are gradually cease to be stimulated "bleached out" rods can produce rhodopsin rods eventually take over in the dim light pupillary dilation - pupils increase size

3. nyctalopia (night blindness) - deficiency in function of rods during dim-light situations a. vitamin A deficiency is general cause III. The Visual Pathway: Photoreceptors to Occipital Cortex photoreceptors (rods & cones) -> bipolar cells -> ganglion cells (axons = optic nerve) -> optic nerves (from each eye retina) optic chiasma (medial fibers cross over) optic tracts (opposite visual field)

RETINA

AXON PATH

THALAMUS AXON PATH CEREBRAL CORTEX

lateral geniculate body of thalamus -> optic radiation (fibers to cortex) occipital lobe - primary visual cortex

other brain areas that receive visual information: 1. superior colliculi - for control of extrinsic eye muscles 2. pretectal nuclei - mediate pupillary light reflexes 3. suprachiasmatic nucleus of hypothalamus - circadian rhythm IV. Binocular Vision and Depth Perception A. binocular vision - two eyes have overlapping regions of the visual field, so that the same point is seen from slightly different angles 1. depth perception - a result of binocular vision in which person can perceive relative distances based on information gathered in both eyes Lecture: Physiology of Hearing and Equilibrium I. Physical Characteristics of Sound A. Sound as Vibration of Air Molecules Traveling in Waves 1. vibration of medium - sound travels in compression waves through a particular medium a. solid-------------> liquid ----------------> gas fastest slowest 2. sound as a wave - the series of high pressure and low pressure areas are called “compressions” and “rarefactions”, respectively a. sine wave - graphic representation of areas of compression and rarefaction of a sound wave wavelength - the distance between 2 areas of compression for a given sound wave frequency - the number of waves that pass a given point in one

b.

c.

second (1/s = 1 Hertz) i. ii. iii. d. short wavelength/high frequency - high pitched tones long wavelength/low frequency - low pitched tones human frequency range - 20Hz - 20,000 Hz (2-3 Hz distinction)

amplitude - intensity of energy in a given wave of sound; signified by height of sine wave i. ii. loudness - subjective interpretation of the intensity of a sound decibel - logarithmic scale to measure the intensity of sound waves Perceived Loudness barely audible 2 X 0 dB 4 X 0 dB 8 X 0 dB 16 X 0 dB

Energy in the Sound Wave 0 dB threshold for audibility 10 dB l0 X 0 dB 20 dB 100 X 0 dB 30 dB 1000 X 0 dB 40 dB 10,000 X 0 dB iii.

human amplitude range - 0 dB - 120 dB (130 dB = pain level)

II.

Transmission of Sound to the Inner Ear air --> external auditory canal --> tympanic membrane (ear drum) --> ossicles (malleus, incus, stapes.) --> oval window of cochlea --> vibration of cochlear fluid --> basilar membrane of cochlea

III.

Resonance of Basilar Membrane & Excitation of Hair Cells A. Resonance of Basilar Membrane 1. 2. 3. vibration of oval window -> perilymph vibration for 20 - 20,000 Hz only, vibration of vestibular membrane vestibular membrane vibration -> endolymph vibration

4.

endolymph vibration -> vibration of basilar membrane 5. basilar membrane “fibers” of different length, thickness, and tension like strings of a piano a. resonance - different fibers of basilar membrane have different “natural frequencies” b. SPECIFIC parts of basilar membrane vibrate only at SPECIFIC frequency (pitch)

B.

Excitation of Hairs Cells of Organ of Corti 1. cochlear hair cells - rest on the basilar membrane, contain "stereocilia" which project into the "tectorial membrane" just above a. b. c. d. basilar m. vibration -> hair cell vibration hair cell vibration -> opening/closing channels depolarization/hyperpolar -> cochlear nerve cochlear nerve impulses -> to brain

IV.

Anatomical Pathway to the Brain

cochlear nerve (vestibulocochlear VIII)-> spiral ganglion --> cochlear nuclei (medulla) --> superior olivary nucleus --> lateral lemniscal tract --> inferior colliculus --> medial geniculate body of thalamus --> auditory cortex (superior temporal lobe) V. Processing of Auditory Information A. B. Perceiving Pitch (Frequency) - location of vibration on the basilar membrane Perceiving Differences in Loudness (Intensity) - amplitude increases, more hair cells of the basilar membrane (with same pitch) are activated localizing Source of Sound 1. superior olivary nucleus - first point where sound from both ears come together

C.

a. b. VI.

relative intensity - the amplitude of sound waves hitting the different ears relative timing - the difference in timing in which a sound reaches both ears

Typical Hearing Disorders A. conduction deafness - disruption in sound vibrations to basilar membrane (ext & mid ear) 1. 2. 3. 4. B. blocked auditory canal (wax, fluid) perforated tympanic membrane (eardrum) otitis media - middle ear infection/inflammation otosclerosis - hardening of the earbone joints

sensorineural deafness - disruption anywhere in pathway from hair cells to the auditory cortex 1. 2. 3. loss of hair cells (explosion, chronic loud noise) damage to vestibulocochlear nerve (VIII) damage to nuclei/tracts to the cortex

C.

tinnitus - chronic perception of clicking or ringing 1. 2. sudden blow to the tympanic membrane gradual deterioration of afferents in cochlear nerve

D.

Menierre's Syndrome - effects both hearing and balance; results in tinnitus, vertigo, and interspersed nausea and vomiting 1. 2. 3. 4. may be too much endolymph beneath basilar membrane symptoms can be treated somewhat with drugs endolymph may be drained periodically hearing loss is progressive

VII.

Equilibrium and Balance: The Vestibular Apparatus A. Linear Movement: The Maculae of the Vestibule 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

c.

i. hair cells - like hair cells of basilar membrane, respond when bent 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

2. 3.

horizontal acceleration - maculae of UTRICLE is in the horizontal plane; hairs bend when motion is FORWARD/BACKWARD vertical acceleration - maculae of SACCULE is in the vertical plane; hairs bend when motion is UP/DOWN

B.

Angular Movement: The Crista of Semicircular Canals 1. semicircular canals - three bony "hula-hoop" extensions of vestibule in three different planes crista ampullaris - like maculae, contain hair cells that respond to flow of endolymph in canals a. cupula - like otolith membrane, gelatinous "cap" into which hair cells project change in angular (rotational) acceleration - movement of the head in non-linear (circular or angular) direction is monitored by three canals vestibular nystagmus - movement of eyes to remain fixed on object when on "merry-go- round" vertigo - false feeling of gravity or motion

2.

3.

4. 5.

C. Equilibrium Pathway: Coordinating Inputs in Brain activated hair cells of crista ampularis -> afferent axon fibers (vestibulocochlear nerve) -> vestibular nuclear complex OR cerebellum 1. vestibular nuclei - also receive input from eyes and somatic proprioceptors; coordinates information to help control motion of eyes, neck, limbs

2. cerebellum - also receives input from eyes and somatic proprioceptors; coordinates information to help regulate head position, posture, and balance D. Problems with Equilibrium 1. 2. dizziness, nausea, imbalance, vomiting motion sickness - conflict between visual/somatic inputs and action of the vestibular apparatus a. Bonine, Dramamine, Scopolamine - block inputs from vestibular apparatus to the brain Lecture: Physiology of Vision I. Overview of Light and Optics A. Wavelength and Colors of Visible Radiation 1. electromagnetic radiation

gamma rays

X-rays UV light VISIBLE LIGHT Infrared Radio Wave medium (380-750 nm) long (102 nm)

short (10-5 nm)

2. wave-photon duality - light travels in wave-like fashion with "single packets" of energy called photons 3. visible spectrum - different colors of light have different wavelengths

Violet 380nm

Blue 480nm

Green 550nm

Yellow 630nm

Orange 680nm

Red 730nm

4. color of an object - the color of an object is determined by which wavelengths are REFLECTED back to the retina (not absorbed by the object) c. white - all wavelengths reflected by object

d. B.

black - all wavelengths absorbed by object

Refraction of Light and Convex Lenses 1. light refraction - light will bend when it passes from one medium (air) into another (lens) e.g. pencil in glass of water 2. convex lens - (thicker at center, tapered at edge) causes light to bend so that it comes together at a focal point a. real image - image at focal point of convex lens ---> inverted & reversed 3. focusing light on the retina a. cornea - constant (unchanging) refraction b. lens - can change refraction and focal length; ciliary muscles change convexity of the lens 4. Focusing for Distance Vision a. far point of vision - distance beyond which lens will not change its shape (about 20 feet) (flattest point of the lens) b. emmetropic eye - normal, healthy eye 5. Focusing for Close Vision

Less than 6 feet, several adjustments are made: a. accommodation of lens - lens shape becomes more convex, light rays bend more sharply, shorter focal length for the closer object (ciliary muscles for lens) i. near point of vision - shortest distance for focusing (maximum convexity of lens); about 8-10 inches; gets worse with age ii. presbyopia - poor close vision in elderly; inelasticity of the lens b. c. C. accommodation of pupils - constriction of pupils; better focus, less divergent rays (constrictor muscles of iris) convergence of eyes - eyes rotate medially to keep image on center of the retina (medial rectus muscles of eyeballs)

Vision Problems Related to Refraction

1.

myopia ("nearsighted") - distant objects are blurred; distant objects are focused in front of the retina, rather than directly on it a. b. eyeball too long; lens too strong concave lens can correct light before eye

2.

hyperopia ("farsightedness") - close objects are blurred; close objects are focused beyond the retina, rather than directly on it b. b. eyeball too short; poor refraction of a lens convex lens can correct light before eye

3.

astigmatism - blurry images at all distances; unequal curves on lens and/or cornea, creating discontinuous image on the retina

II.

Anatomy, Biochemistry, & Physiology of Photoreceptors B. Functional Anatomy of Photoreceptors

1. General Structure of Rods and Cones "pigmented base" of retina outer segment (pigmented discs) connecting stalk inner segment (mitochondria) outer fiber cell body (nucleus) inner fiber synaptic ending bipolar cell ganglion cell (axons carried to brain by optic nerve) a. outer segment - contain membrane-bound discs with pigments that absorb and react to light i. rods - pigment discs stacked like pennies all the way to the base, membranes are DISTINCT from the plasma membrane 1. 2. 3. 4. sensitive to dim light (night vision) respond to ALL wavelengths (colors) only "grey" information to the brain 100 rods per ganglion cell to brain

"neural layer"

5. widely spread throughout the retina 6. not good for visual acuity ii. cones - pigment discs taper off toward the base, membranes are CONTINUOUS with the plasma membrane 1. 2. 3. 4. 5. 6. B. require bright light for stimulation different cones have different pigments specific for certain wavelengths (colors) can convey color information to brain 1-3 cones per ganglion cell to brain primarily concentrated in fovea (center) essential for visual acuity

Biochemistry of Visual Pigments 1. 2. opsin - transmembrane protein in the membrane of pigmented discs of rods and cones retinal - light absorbing molecule that changes shape when struck by a photon of light a. b. c. vitamin A - precursor to retinal (eat your carrots!!!!!!) 11-cis isomer of retinal - non-activated form of retinal, prior to absorption of photon energy; has a "kinked" double bond all trans isomer of retinal - activated form of retinal, after struck by photon of light; double bond straightens out

C.

Excitation of Rods 1. 2. rhodopsin - visual pigment in rods; in membranes of pigmented discs of outer segment bleaching of pigment - breakdown of rhodopsin after the absorption of light rhodopsin  light all-trans retinal + scotopsin

11-cis retinal  + scotopsin 3.

all-trans retinal - causes HYPERPOLARIZATION of rod a. b. c. d. Na+ channels (open in dark) are closed rod is hyperpolarized (increased negativity) Ca++ channels in synapse close less neurotransmitter released by the rod

D.

Excitation of Cones 1. photopsins - 3 distinct pigments in cones are sensitive to 3 different parts of visible spectrum a. b. c. blue cones - maximum sensitivity at 455 nm green cones - maximum sensitivity at 530 nm red cones - maximum sensitivity at 625 nm

2. different colors - differential activation of each of the three different cones 3. color blindness inherit gene for one of the photon proteins that is deficient (mainly male), most common are red and green mutations E. Light and Dark Adaptation of Rhodopsin 1. light adaptation - very dark  very bright a. b. c. d. e. rhodopsin in rods is quickly bleached out sensitivity to shallow light disappears rods are inhibited by other retinal cells cones are activated to take over (5 mins.) consensual pupil reflex - constriction

2. dark adaptation - very bright  very dark a. b. c. d. cones are gradually cease to be stimulated "bleached out" rods can produce rhodopsin rods eventually take over in the dim light pupillary dilation - pupils increase size

3. nyctalopia (night blindness) - deficiency in function of rods during dim-light situations a. vitamin A deficiency is general cause III. The Visual Pathway: Photoreceptors to Occipital Cortex photoreceptors (rods & cones) -> bipolar cells -> ganglion cells (axons = optic nerve) -> optic nerves (from each eye retina) optic chiasma (medial fibers cross over) optic tracts (opposite visual field)

RETINA

AXON PATH

THALAMUS AXON PATH CEREBRAL CORTEX

lateral geniculate body of thalamus -> optic radiation (fibers to cortex) occipital lobe - primary visual cortex

other brain areas that receive visual information: 1. superior colliculi - for control of extrinsic eye muscles 2. pretectal nuclei - mediate pupillary light reflexes 3. suprachiasmatic nucleus of hypothalamus - circadian rhythm IV. Binocular Vision and Depth Perception A. binocular vision - two eyes have overlapping regions of the visual field, so that the same point is seen from slightly different angles 1. depth perception - a result of binocular vision in which person can perceive relative distances based on information gathered in both eyes http://faculty.lacitycollege.edu Lecture: Plasma Membrane and Transport I. Structure of the Plasma Membrane A. plasma membrane - the surface encapsulating a cell

B.

Fluid Mosaic Model 1. bilayer of phospholipids a. hydrophilic heads - P04 end "water" "loving" attracted to water on inner/outer parts of cell

b. hydrophobic tails - fatty acids "water" "fearing" attracted to each other on inside of bilayer c. glycolipids - some carbohydrates attached to outer lipids (involved in cell to cell recognition) d. cholesterol - regulates fluidity of

membrane

2. proteins interspersed throughout the membrane

a. functions of membrane proteins i. hormones, neurotransmitters ii. reactions in & out of cell iii. and molecules b. integral proteins - inserted into the bilayer i. transmembrane - across entire bilayer

receptors enzymes transport - ions

c. peripheral proteins - on inner & outer surface d. glycoproteins - carbohydrates on outer surface i. glycocalyx - outer carbohydrate coat (cell recognition and identification) 3.plasma membrane is fluid: it can easily shift & flow a. two layers can slide over one another b. some proteins float freely throughout membrane c. many proteins attached to cytoskeleton i. allows for regional specialization 4. Features of Plasma Membrane a. microvilli - fingerlike extensions of cell i. found in kidney and intestine ii. increases surface area for absorption iii. actin filaments for support b. tight junctions - cell-cell adhesion proteins i. generally at surface of epithelium ii. prevent passage between cells iii. "seal" layer of cells into a sheet

c. desmosomes - anchor cells to cells basement i. carbohydrates of glycoprotein intermingle ii. keratin filaments anchor to cytoplasm iii. hemidesmosome - anchor to basement membrane II. Plasma Membrane Transport A. General Features 1. interstitial fluid - bathes all cells and tissues a. released by capillaries into organs/tissues b. recaptured by lymph vessels back to heart c. contains salts, nutrients, hormones, etc. 2. selectively permeable - only certain things pass a. passive transport - nature does the work b. active transport - cell must use energy (ATP) B. Passive Transport Processes (no cellular energy required) 1. diffusion - movement of particles from area of HIGH concentration to area of LOW concentration until equal a. concentration gradient - difference in concentration between HIGH and LOW areas i. larger gradient larger driving force ii. faster = higher temperature or smaller particle 2. simple diffusion across the cell membrane a. nonpolar molecules (oxygen, carbon dioxide, urea) i. oxygen blood (high)  cells (low) ii. CO2 iii. urea

cells (high)  blood (low) cells (high)  blood

(low) b. fat soluble molecules (small fats and steroids) 3. osmosis - the movement of a solvent (such as WATER) from an area of LOW solute concentration (such as NaCl) to an area of HIGH solute concentration solution = solvent + solute (dissolving liquid) (dissolved particles) a. molarity - moles of solute / liters of solvent (moles/liter = Molar) i. mole - grams of substance = mol. wt. substance 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)

b. osmolarity - measure of concentration of particles in a solution i. 1 molar Glucose = 1 osmol Glucose ii.1 molar NaCl = 2 osmol NaCl WHY? in water NaCl dissociates  Na+ + Cl(for each salt molecule their are 2 parts) Movement Across Membrane Permeable to Water Only (not solutes) Conditions Water Movement Terminology osmo(in) = osmo(out) isotonic osmo(in) > osmo(out) inside is hypertonic

no net movement water moves IN

osmo(in) < osmo(out) inside is hypotonic c. osmotic pressure - driving force generated by the concentration gradient

water moves OUT

*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

e. observable implications of osmosis i. crenate - water moves out and cell shrinks ii. lyse - water moves in and cell bursts f. clinical implications of osmosis i. isotonic I.V. - Ringers (0.9% NaCl; 5% glucose) ii. hypertonic I.V. - to treat edema (water excess) iii. hypotonic I.V. - to treat dehydration

4. filtration - hydrostatic pressure > osmotic pressure (Squeezing a leaky water balloon) a. WATER moves from HIGHER osmo  LOWER osmo 5. facilitated diffusion - see-saw protein carries across or channels allow through (goes with the concentration gradient so it is still a form of passive transport) a. carrier protein - "open outside" <-> "open inside" i. very specific for the molecule transported ii. uses energy of natural diffusion (waterwheel) iii. glucose carrier is typical b. protein channels - passage of charged & polar i. Na+, K+, Cl- channels are very specific can be opened or closed on command C. Active Transport Processes (energy of the cell required)

1. active transport - transport solutes against a concentration gradient (goes against diffusion) a. solute pumps - Na+, K+, Ca++, amino acids (relies on ATP energy source) i. rely on energy of ATP to overcome forces of nature ii. uniport - one specific particle only iii. coupled system - two particles together symport - same direction antiport - opposite directions 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) b. endocytosis - engulfment by cell membrane pouch which then buds off into the cytoplasm i. phagocytosis ("eat" "cell"" process") - plasma membrane raps around large mass (bacteria, dead cell, cell debris) phagosome  lysosome (digestive enzymes)

macrophages - immune cells that engulf ii. pinocytosis - "drink" "cell"" process" iii. receptor-mediated endocytosis receptors on the cell surface bind to desired molecule before the engulfment 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 2. Results in NET flow of positive charge out of the cell 1 cycle = 3Na+ out & 2K+ in

3. Na+ Channels normally closed so that Na+ cannot easily move back into the cell.

4. K+ Channels normally slightly open so that K+ can slowly leak out 5. The net movement of Na+ and leaking of K+ to the outside of the cell causes a POTENTIAL DIFFERENCE (voltage) across the membrane. 6. resting membrane potentials for cells generally range: -20 mV to -200mV 7. electrochemical gradient - charge & concentration i. Na : {electro-IN; chemical-IN} ii. K+: {chemical-OUT = electro-IN}
+

IV.

Functions of Glycoproteins on Cell Membrane (Glycocalyx)

A. Determination of ABO Blood Types 1. cell (RBC) a. signature for immune response of foreign blood B. Binding of Dangerous Toxins Sugar moiety on glycoprotein of red blood

1. proteins of cholera and tetanus bind to cell by identifying specific carbohydrates on proteins

C.

Identification of Specific Cell Types 1. Sperm knows egg by specific glycoproteins 2. Cell-cell interaction during embryogenesis and tissue differentiation 3. Immune cells identifying foreign cells and material such as bacteria, viruses, and cancer cells /gonsalgg/phlect1.html Lecture: Muscle Physiology

I.

Anatomy of Skeletal Muscle CELL (Muscle Fiber) A. 1. 2. 3. 4. 5. 6. 7. B. 1. 2. 3. General Features multinucleated cells (syncytium: from fusion) sarcolemma - special name for plasma membrane very long compared to other cells (1 - 300 mm) not unusually wide diameter (10 - 100 microns) sarcoplasm - rich in glycogen and myoglobin myoglobin - stores oxygen; similar to hemoglobin special structures: myofibrils and sarcoplasmic reticulum Ultrastructure of Myofibrils ¼ muscle cell contains many parallel myofibrils myofibrils have DARK bands (A bands) and LIGHT bands (I bands) that cause "striated" appearance of muscle A band and I band result from the arrangement of overlapping and nonoverlapping regions of two types of myofilaments a. b. 4. thick filaments (myosin) thin filaments (actin)

sarcomere - smallest contractile unit of muscle cell a. Z-line - connection of actin filaments; dividing line between two adjacent sarcomeres b. M-line - connection of myosin filaments c. H-zone - non-overlapping region of the myosin filaments around the M-line d. A-band - length of myosin

filaments e. overlapping actin filaments

I-band - length of non-

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. C. Molecular Structure of Actin & Myosin Filaments 1. thick filaments (myosin filaments) 12-16 nm a. composed of about 200 myosin proteins i. myosin has a golf club like shape ii. 2 heads (cross bridges) - can bind to the actin filaments and use ATP iii. tail - shaft of the thick filament 2. thin filaments (actin filaments) 5-7 nm a. 2 helical chains of F actin (G actin subunits) I. G actin can bind with myosin heads ii. tropomyosin - rod-like protein that helps to stiffen F actin structure iii. troponin - globular protein that can bind Ca++ to regulate actin/myosin binding D. Sarcoplasmic Reticulum and T Tubules 1. sarcoplasmic reticulum - smooth ER that houses Ca++ a. surrounds each myofibril b. fused to each other at H zones and A/I bands c. terminal cisternae - around A/I bands 2. T (transverse) Tubules - passageways from extracellular space to the terminal cisternae of SR a. passage of nerve message directly to SR b. passage of glucose, oxygen, salts to fiber II. Contraction of Skeletal Muscle Cell A. Sliding Filament Model (Actin/Myosin Sliding Mechanism) 1.Ca++ released from sarcoplasmic reticulum 2.Ca++ binds to TnC region of Troponin 3.Troponin changes shape, moving Tropomyosin, exposing binding site on

actin filament 4. Attachment - myosin head with ADP + Pi binds actin 5. Power Stroke - myosin head bends, pulling along the actin filament, ADP + Pi are released 6. Detachment - ATP binds to the myosin head, causing detachment from Actin 7. Re-cocking the Head - hydrolysis of ATP  ADP + P releases energy to re-cock the myosin 8. some myosin heads are in contact with actin at all times, allowing "walking motion" to occur 9. 1 cycle = 1 % muscle contraction 10. motion continues until no more ATP is present or Ca++ levels drop by re-uptake into SR 11. rigor mortis - muscles stiffen because Myosin heads remain attached to the Actin filaments III. A. 1. Regulation of Contraction of a Single Skeletal Muscle Cell Neuromuscular Junction (nmj) neuromuscular junction - nerve/muscle intersection a. 1 motor neuron/axon supplies several fibers b. 1 centrally located junction per fiber c. synaptic vesicles - sacs that contain acetylcholine (AChneurotransmitter) d. synaptic cleft - space between the axon terminal and the sarcolemma of the muscle cell e. motor end plate - highly folded part of sarcolemma beneath the synaptic cleft; rich in ACh receptors Signal Transmission and Electrical Excitation of Muscle

B.

1. Nerve Signal Causes Release of ACh from Axon End a. action potential along axon causes depolarization of axon terminal b. decreased membrane potential causes Voltage-Dependent Ca++ Channels on axon terminal to open c. Ca++ influx into axon terminal causes exocytosis of ACh containing synaptic vesicles d. ACh diffuses across the synaptic cleft to bind to ACh receptors of the motor end plate

2.

Electrical Excitation of the Sarcolemma I. Like most cell membranes, the sarcolemma of muscle cells is polarized: it has more negative charge inside than outside. II. ACh triggers an Electrical Excitation of the sarcolemma by opening chemically gated Na+ Channels, allowing positive charge to rush into the cell. The muscle cell becomes less negative or becomes depolarized. a. ACh binds to ACh Receptors which open ACh-Dependent Na+ Channels b. these Na+ Channels allow Na+ to flow into the muscle cell, causing depolarization c. depolarization at the neuromuscular junctions spreads to adjacent sites d. Vo1tage-Dependent Na+ Channels at the adjacent sites open, allowing more Na+ in e. A wave of depolarization therefore spreads across the entire cell f. this cannot be stopped and is called an all-or-none response g. entire process occurs in about 1 millisecond (1/1000 second) h. A refractory period occurs in which the muscle cell must repolarize to its resting state. This happens when the Voltage-Dependent Na+ Channels close, VoltageDependent K+ Channels open, and the Na+-K+ ATPase pump rebalances the ion concentrations. Repolarization generally takes very little time (3 milliseconds), while contraction can last up to 100 milliseconds (1/10 sec). Limits how fast the cell can "re-fire" and contract!

3.

Importance of Acetylcholine and Neuromuscular Junction a. After binding to ACh Receptors on sarcolemma, ACh is quickly broken down by an enzyme known as Acetylcholinesterase (AChE) b. myasthenia gravis - autoimmune disease where immune system attacks ACh Receptors c. ACh Antagonists - chemicals that block an ACh receptor

i.

snake venoms - curare and other venoms

4. Coupling of Excitation and Contraction a. latent period - time between excitation & contraction

i. action potential passes down the T Tubules from the sarcolemma surface ii. T Tubule depolarization causes the release of Ca++ from the sarcoplasmic reticulum iii. Ca++ increase causes uncoupling of Troponin and sliding of filaments described above iv. ATP-Dependent Ca++ Pumps pump the Ca++ back into the sarcoplasmic reticulum v. Low Ca++ levels allows Troponin/Tropomyosin blockade of actin and muscle relaxes b. Calcium Sequesters - bind Ca++ in the cell so it will not form Calcium Phosphate crystals i. calmodulin and calsequestrin REMEMBER: A Skeletal Muscle CELL (Fiber) will contract in an All-or-None fashion when ITS motor neuron stimulates it to fire by releasing ACh!!!!!!!!!! IV. Contraction of a Skeletal MUSCLE

A. Motor Unit - a single motor neuron and all of the muscle cells stimulated by it 1. # muscle cells per motor neuron = 4 - 400 i. muscles of fine control (fingers, eyes and face): fewer muscle cells per neuron ii. muscles of posture and gross movement (gluteus maximus): more muscle cells per neuron 2. axon terminals are distributed on muscle fibers throughout the muscle (not one region)

i. stimulation of one motor unit causes weak contraction throughout the whole muscle B. Muscle Twitch - the response of a muscle to a single short electrical stimulus 1. strong twitch - many motor units activated; weak twitch - few motor units are activated 2. latent period (3 ms) - time after stimulation for coupling to occur and contraction to start 3. contraction period (10 - 100 ms) - from beginning of contraction to maximum force (tension) 4. relaxation period (10 - 100 ms) - time from maximum force to original relaxed state C. Graded Muscle Responses (smooth, not All-or-None) 1. Frequency of Stimulation (Wave Summation) - a motor unit may be stimulated over and over again so no relaxation period is possible i. frequency of stimulation cannot be greater than 1 every 3 ms (REFRACTORY PERIOD) ii. motor neurons generally deliver action potentials in volleys with varying frequency iii. tetanus - smooth muscle contraction that occurs when summation is so great that the relaxation period disappears 2. Summation of Multiple Motor Units - as strength of stimulus is increased, more and more motor units are activated in the muscle itself i. threshold stimulus - level of stimulus at which first motor units are activated ii. maximal stimulus - level of stimulus at which all motor units of a muscle are activated Muscles of the hand show summation of motor units well. When weak force and delicate motion is needed, few motor units are activated (those with the least # muscle fibers per motor unit). However, when great force is needed, the strength of the stimulus is increased to recruit more motor units (with many muscle fibers per motor unit). 3. Asynchronous Motor Unit Summation - motor units activated in different cycles "average out to produce a smooth muscle contraction

D. Treppe: The Staircase Effect - When a muscle is first used, it will show a gradual increase in force with a maximal stimulus until it is 'warmed up". E. Muscle Tone - slightly contracted state of muscle that is maintained by reflexes originating in the spinal cord. Maintains posture and readiness for active contraction. F. Isometric and Isotonic Contractions a. muscle tension - force generated by a muscle b. load - force resisting movement of a muscle. Muscle tension must be greater than load to move it.

c. isometric contraction - muscle doesn’t change length (trying to lift a box that is too heavy) d. isotonic contraction - muscle moves the load (doing bicep curls with weights) V Force, Velocity, and Duration of Skeletal Muscle Contraction

A. Force of Contraction - determined by several factors 1. number of motor units activated 2. size of muscle (in cross section) a. size increased by increasing the SIZE of individual muscle cells (not increasing cell #) 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 4. Degree of Muscle Stretch (Actin-Myosin Overlap) a. optimal force can be generated when muscle is between 80 - 120% of resting length B. Velocity and Duration of Contraction

1. Effect of the Load on a Muscle a. smaller the load, faster the contraction

b. larger load: slower contraction/less duration 2. Type of Muscle Fiber a. Red Slow-Twitch Fibers (small, red) i. slow twitch; slow acting myosin ATPases ii lots of myoglobin (red) to store oxygen iii. many mitochondria, active enzymes iv. use fat as primary fuel source v. very aerobic, long duration contraction b. White Fast-Twitch Fibers (large, pale) i. fast twitch; fast acting myosin ATPases ii. few mitochondria, primarily anaerobic iii. glycogen stores used for anaerobic resp. iv. lactic acid produced, fatigues quickly V. rapid, intense, short duration contraction c. Intermediate Fast-Twitch Fibers (medium, pink) i. fast twitch; fast acting myosin ATPases ii. aerobic with myoglobin present iii. somewhat resistant to fatigue 3. Muscle Composition by Fiber Type a. most muscles have combinations of all 3 types b. people differences are genetically determined VI. Effect of Exercise (and no exercise) on Skeletal Muscle A. Physiological Adaptations from Exercise 1. aerobic exercise - that requiring steady oxygen a. capillaries, myoglobin, mitochondria increase b. better endurance and strength 2. resistance exercise - short duration, high load a. actin, myosin, myofibers all increase b. hypertrophy - increase in muscle size b. glycogen stores and connective tissue increase

B Disuse Atrophy 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 A. Pathways for Synthesis of ATP for Contraction 1. ADP - Creatine Phosphate (Immediate Reserve) Creatine-phosphate + ADP  Creatine + ATP (Creatine Kinase) a. used for first 3 - 5 seconds of activity while respiration processes are warming up 2. Anaerobic Respiration (Lactic Acid Fermentation) (Insufficent Oxygen Supply) glycolyis glucose  pyruvic acid (INSUFFICIENT oxygen) pyruvic acid  lactic acid ** ** ** ** ** used for short-term, intense activity (10 - 15 sec) used when oxygen demand CANNOT be met by resp/circ yields only 2 ATP per glucose lactic acid is reconverted to pyruvic acid when oxygen becomes available pyruvic acid then broken down all the way to C02 to release 34 more ATP

3. Aerobic Respiration (Sufficient Oxygen Supply) glycolyis glucose  pyruvic acid (SUFFICIENT oxygen) pyruvic acid  H20 + C02 ** ** ** ** ** used for more prolonged, steady activity (walking) used when oxygen demand CAN be met by resp/circ yields 36-38 ATP per glucose (18-19 X anaerobic!!!) glycolysis occurs in the sarcoplasm oxidative reactions, using pyruvic acid to make more ATP, occurs in the mitochondria

B. Muscle Fatigue, Oxygen Debt, and Heat Production 1 muscle fatigue - inability of a muscle to contract on a physiological basis

a. when there is less ATP than the muscle requires b. lactic acid decreases pH, affects enzymes c. salt loss (Na+, K+, Ca++); ionic imbalance d. ATP required to drive Na+-K+ ATPase Pump 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: a. restore reserves of ATP and Creatine Phosphate b. lactic acid converted back to pyruvic acid c. restore reserves of glucose and glycogen d. restore oxygen reserves (stored in myoglobin) e. athletic conditioning increases the efficiency of oxygen use, thereby reducing oxygen debt 4. heat production - muscle contraction produces heat which can be dangerous (extreme body temperature) or can be useful (generate heat by shivering) Lecture: Circulatory Physiology I. Factors Involved in Blood Circulation A. B. Blood Flow - the actual VOLUME of blood moving through a particular site (vessel or organ) over a certain TIME period (liter/hour, ml/min) 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) C. Resistance to Flow (Peripheral Resistance) - the FORCE resisting the flow of blood through a vessel (usually from friction)

1. viscosity - a measure of the "thickness" or "stickiness" of a fluid flowing through a pipe a. b. V water < V blood < V toothpaste water flows easier than blood

2. tube length - the longer the vessel, the greater the drop in pressure due to friction 3. D. tube diameter - smaller diameter = greater friction

Relation Between Blood Flow, Pressure, Resistance

difference in blood pressure ( P) Blood Flow (F) = peripheral resistance (R) a. b. c. d. II. increased P -> increased flow decreased P -> decreased flow increased R (vasoconstriction) -> DECREASED flow decreased R (vasodilation) -> INCREASED flow

Systemic Blood Pressure A. Blood Pressure Near the Heart 1. 2. 3. HEART produces blood pressure by pumping the blood Blood pressure decreases with distance from Heart systolic arterial blood pressure - pressure in aorta (& major arteries) in middle of ventricular contraction (120 mm Hg in healthy adult) diastolic arterial blood pressure - pressure in aorta (& major arteries) during ventricular diastole, when semilunar valves are closed (80 mm Hg in healthy adult) mean arterial pressure (MAP) - the "average" blood pressure produced by the heart (93 mm Hg in healthy adult) mean arterial pressure = diastolic pressure + 1/3 pulse pressure ** 6. pulse pressure = systolic pressure - diastolic pressure

4.

5.

blood pressure decreases throughout system L ventricle arteries arterioles capillaries venous R atrium -->120 mm Hg -->120 - 60 mm Hg -->60 - 40 mm Hg -->40 - 20 mm Hg -->20 - 10 mm Hg -->10 - 0 mm Hg

7.

venous return - venous blood pressure is so low, other factors contribute to venous blood flow

a. respiratory pump - breathing action of thorax "squeezes" blood back toward the heart

b. muscular pump - contraction/relaxation of skeletal muscles "milk" blood up veins to heart III. Factors Affecting Blood Pressure A. Cardiac Output ( = stroke volume X heart rate) CO = = 1. 2. 3. B. SV (ml/beat) x HR (beats/min) 70 ml/beat x 60 beats/min = 4200 ml/min

increased cardiac output -> increased blood pressure increased stroke volume -> increased blood pressure increased heart rate -> increased blood pressure

Peripheral Resistance

1. arteriole constriction ---> increased blood pressure 2. resistance inversely proportional to the "fourth power" of the radius change C. Blood Volume 1. 2. 3. 4. IV. hemorrhage - decrease in blood pressure salt/fluid - increase in blood pressure polycythemia - increase in blood viscosity RBC anemia - decrease in blood viscosity

Regulation of Blood Pressure A. Nervous System Control 1. 2. 3. control of arteriole diameter directs blood flow to proper organs and tissues that need it REFLEX PATHWAY: baroreceptors/chemoreceptors/brain afferent nerve fibers medulla (vasomotor center) vasomotor (efferent) nerve fibers smooth muscle of arterioles B. --> --> --> -->

Vasomotor Fibers to Smooth Muscle of Arterioles 1. sympathetic fibers that release norepinephrine (NE); cause vasoconstriction of arterioles

C.

Vasomotor Center of the Medulla

1. sympathetic neuron cell bodies in the medulla 2. receive input from baroreceptors, chemoreceptors, and brain 3. vasomotor tone - general constricted state of arterioles set by vasomotor center D. Baroreceptors

1. blood pressure receptors large arteries (carotid sinuses, aortic arch, neck/thorax arteries) 2. send blood pressure information to vasomotor center of medulla increased pressure --> inhibits vasomotor center center -> vasodilation E. Chemoreceptors 1. 2. blood to lungs quickly F. Higher Brain Centers Control on BP 1. G. hypothalamus & cortex also effect vasomotor area located in aortic arch and carotid arteries a. carotid and aortic bodies monitor OXYGEN and pH levels of the blood low OXYGEN or low pH -------> increase blood pressure, return --> stimulates vasomotor vasoconstriction --> decreased pressure

Chemical Controls of Blood Pressure 1. hormones of adrenal medulla - "fight-or-flight" response to fear; release of norepinephrine and epinephrine from adrenal medulla; causes vasoconstriction and increased BP atrial natriuretic factor (ANF) - secreted by the atria of the heart, promotes general decline in blood pressure kidney releasing more Na+ and water, reducing fluid volume antidiuretic hormone (ADH) - released by the hypothalamus, causes increase in blood pressure by getting the kidneys to conserve water in the body; e.g. during hypotensive situations

2.

3.

4.

endothelium derived factors a. b. endothelin - strong vasoconstrictor endothelium derived relaxing factor - vasodilation

5. H.

alcohol - causes vasodilation

Renal (Kidney) Regulation 1. direct regulation - fluid loss through urine a. b. 2. low pressure/volume --> conserve water high pressure/volume --> release more water

renin-angiotensin mechanism low blood pressure --> release of renin --> formation of angiotensin II--> vasoconstriction release of aldosterone --> Na+/water reabsorption (by kidney)

V.

Variations in Blood Pressure A. Measuring Blood Pressure vital signs - blood pressure, pulse, respiratory rate, and body auscultory method of blood pressure measurement a. b. c. d. B. “sphygmomanometer” wrapped around upper arm inflate above systolic pressure of brachial a. pressure released, first sounds - systolic pr. disappearance of sounds - diastolic pr.

1. temperature 2.

Hypotension (below normal blood pressure, < 100/60) 1. 2. 3. factors - age, physical conditioning, illness orthostatic hypotension - generally in elderly, drop in blood pressure during postural changes chronic hypotension - ongoing low blood pressure a. low blood protein levels (nutrition)

b. c. d. C.

Addison’s disease (adrenal cortex malfunction) hypothyroidism also sign of various types of cancer

Hypertension (above normal blood pressure at rest, > 140/90) 1. 2. factors - weight, exercise, emotions, stress chronic hypertension - ongoing high blood pressure a. b. c. d. prevalent in obese and elderly leads to heart disease, renal failure, stroke also leads to more arteriosclerosis primary hypertension - unidentified source i. ii. iii. iv. e. high Na+, cholesterol, fat levels clear genetic component (in families) diuretics - promote water removal NE blockers - slow vasoconstriction

secondary hypertension - identifiable disorder i. ii. iii. kidney disorders endocrine (hormone) disorders arteriosclerosis

VI.

Blood Flow in the Body A. General Features 1. 2. 3. 4. 5. delivery of oxygen and removal of carbon dioxide gas exchange in the lungs absorption and delivery of nutrients from GI tract processing/waste removal in the kidneys normal blood flow at rest abdominal organs 24% skeletal muscle 20% kidneys 20% brain 13% heart 4% other 15%

B.

Velocity of Blood Flow 1. velocity directly related to the TOTAL cross-sectional area of the vessel(s)

FASTEST SLOWEST C.

aorta arteries arterioles capillaries

40-50 cm/s 20-40 cm/s 1-20 cm/s 0.1-1 cm/s

Local Regulation of Blood Flow autoregulation - regulation of blood flow by altering arteriole a. b. c. 2. oxygen and carbon dioxide levels prostaglandins, histamines, kinins needy areas --> more blood flow

1. diameter

myogenic response - change in flow through arteriole in response to stretch of smooth muscle

3. reactive hyperemia - increase in blood flow to area where an occlusion has occurred 4. D. increased vasculature - results from prolonged lack of oxygen/nutrients to an area (eg. heart)

Blood Flow to Skeletal Muscles

1. active (exercise) hyperemia - increased blood flow to muscles during heavy activity b. E. a. decreased oxygen and increased lactic acid visceral organ blood flow is decreased

Blood Flow to The Brain 2. 3. 1. MUST maintain constant blood flow (750 ml/min) sensitive to low pH and high carbon dioxide blood pressure tightly regulated in the brain a. fainting -> below 60 mm Hg b. edema (brain swelling) -> above 180 mm Hg

F.

Blood Flow to The Skin 1. intimately involved in temperature regulation

increased body temperature -> hypothalamic inhibition of vasomotor area -> vasodilation of vessels in skin ->

increased blood flow -> sweating -> (bradykinin -> more vasodilation) G. Blood Flow to the Lungs 1. 2. H. short pathway from heart, less pressure required low oxygen level --> vasoconstriction

Blood Flow to the Heart 1. 2. blood to coronary arteries during diastole vasodilation from ADP and carbon dioxide

VII.

Blood Flow in the Capillaries A. Exchange of Gases and Nutrients 1. diffusion - all molecules move DOWN the concentration gradient (from HIGH to LOW) into or out of the blood 2. oxygen/nutrients cells) carbon dioxide/ wastes B. itself a. filtration pressure - the pressure forcing fluid and solutes through capillary clefts 2. osmotic pressure - force driving fluid in the direction of HIGHER solute concentration 3. movement out: Hydrostatic pressure > Osmotic difference movement in : Hydrostatic pressure < Osmotic difference 4. C. normal fluid movement 1.5 ml/min in the entire body Fluid Movements 1. hydrostatic pressure - force from the capillary wall on the blood (blood (body cells ------> body ------> blood)

Circulatory Shock

1. circulatory shock - blood pressure gets so low that blood will not flow adequately 2. hypovolemic shock - circulatory shock resulting from loss of fluid (bleeding, diarrhea, burn) a. heart rate increases rapidly

b.

general vasoconstriction of vessels

3. vascular shock - extreme vasodilation causes sudden drop in blood pressure a. snake and spider bites with NE blockers b. septicemia - bacterial infection 4. pressure I. cardiogenic shock - heart is unable to provide sufficient blood Lecture: Physiology of Digestion Overview of Digestive System A. Structures of Digestive System 1. alimentary canal (gastrointestinal [GI] tract) a. b. c. 2. digestion - break down molecules absorption - move into circulatory system mouth, pharynx, esophagus, stomach, small intestine, large intestine, anus

accessory digestive organs a. b. function - assist in breakdown and absorption of foodstuffs teeth, tongue, gallbladder, salivary glands, liver, pancreas

B.

Primary Functions of Digestive System 1. 2. 3. ingestion - getting food into the GI tract (eating) propulsion - moving food along the tract a. swallowing and peristalsis (wave-like motion) mechanical digestion - the physical grinding and churning of foodstuffs to breakdown and expose to enzymes and the surface of the GI tract chemical digestion - breakdown of larger molecules into absorbable parts by enzymatic action absorption - transport of digested molecules, vitamins, minerals, water, into blood defecation - elimination of unused foodstuff (feces)

4. 5. 6.

C.

Control of Conditions in the GI Tract 1. mechanoreceptors and chemoreceptors respond to: a. b. c. 2. stretching of the lumen by foodstuffs solute concentration and pH within the lumen presence of digestible and digested molecules

actions initiated by these receptors: a. b. c. d. activate/inhibit secretions into the lumen activate/inhibit muscular "mixing" activity activate/inhibit secretion of hormones activate/inhibit local "nerve plexuses"

3.

types of digestive reflex processes: a. b. short reflex - controlled by "nerve plexus" within the GI tract (enteric plexus) long reflex - those involving the CNS and extrinsic autonomic nerves

II.

Digestive Processes Occurring in the Mouth, Pharynx, Esophagus A. Composition of Saliva & Control of Salivation 1. major components of saliva: a. b. c. d. e. f. 2. water (97-99.5%) electrolytes: Na+, K+, Cl-, PO4mucin - protein that forms thick, slimy mucus IgA antibodies - immune defense lysozyme - antibacterial enzyme salivary amylase - starts breakdown of carbo's

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 SYMPATHETIC nerve activation 

decreased salivation B. 1. Mechanical Processes mastication (chewing) - cheeks, tongue, and teeth involved in both voluntary and involuntary grinding, ripping, and tearing of foodstuffs deglutition (swallowing) - moving "bolus" on its way a. b. tongue compacts ground food into a "bolus" buccal phase (voluntary) tongue against hard palate tongue contraction bolus forced into oropharynx c. pharyngeal-esophageal phase (involuntary)  III. tongue blocks off mouth soft palate blocks off nasopharyx epiglottis blocks off trachea peristaltic waves moves food to stomach

2.

Regulation of Gastric Secretion, Motility, and Emptying A. Regulation of Gastric Secretion ("Gastric Juice") 1. cephalic (reflex) phase sight, aroma, taste, thought  hypothalamus gustatory centers  vagal nuclei of medulla  vagus nerve (parasympathetic)  increased gastric secretion 2. gastric phase a. food reaches the stomach hormonal mechanism digested proteins --->

neural mechanism distention & low acidity --->

vagal afferents to medulla ---> vagal efferents to stomach ---> parasympathetic ACh release ---> increased gastric secretion

increase in pH ---> gastrin released ---> enzymes & HCl released

b.

control of HCl secreting parietal cells i. ii. gastrin, histamine, & ACh increase the release of HCl from parietal cells H+ comes from carbonic acid release

3.

intestinal phase inhibitory phase inhibition of vagal nuclei inhibition of local reflexes activation of sympathetics release of inhibitory hormones: (secretin, cholecystokinin CCK, gastric inhibitory peptide GIP)

excitatory phase chyme enters the duodenum -> release of intestinal gastrin -> continued gastric secretion

B.

Gastric Motility and Emptying 1. 2. 3. 4. 5. receptive relaxation - trilayer of muscles in wall of the stomach relax to allow filling to occur plasticity - smooth muscle tension specially regulated to prevent regurgitation of food basic electrical rhythm - pacemaker cells of longitudinal muscle allow rhythmic contractions emptying to duodenum - regulated by amount and type of chyme entering into the duodenum; faster with high carbo, slower with higher fats vomiting (emesis) - irritants activate neurons which stimulate the "emetic center" of medulla

IV.

Content of Bile and Bile Release into Small Intestine

A.

Content of Bile (made in Liver, released by Gall Bladder) 1. 2. bile salts, bile pigments, cholesterol, neutral fats, phospholipids, electrolytes bile salts - derivatives of cholesterol (cholic acid, chenodeoxycholic acid) a. emulsify fats - separate fats into tiny droplets for digestion & absorption b. enterohepatic circulation - conservation of bile salts by re-processing i. ii. iii. 3. reabsorbed in distal small intestine to liver via hepatic portal blood resecreted as bile from gall bladder

bile pigment (bilirubin) - waste product of heme from brokendown erythrocytes a. urobilinogen - breakdown product of bilirubin, causes darker coloration of feces

B.

Regulation of Bile Release to Small Intestine 1. 2. 3. hepatocytes - cells of the liver that produce 0.5-1.0 liters of bile each day parasympathetic - stimulates gall bladder release cholecystokinin (CCK) - hormone released by cells of the mucosa of the duodenum

acidic, fatty chyme enters duodenum  duodenal mucosa secretes CCK  a. b. c. 4. V. gall bladder contracts to release bile pancreas secretes pancreatic juices hepatopancreatic sphincter opens

gallstones - crystallized formation of cholesterol and salts, causing obstruction of bile release

Composition of Pancreatic Juice and Regulation of Secretion A. Composition of Pancreatic Juice 1. 2. 1.2 - 1.5 liters per day water and electrolytes (mainly bicarbonate ions)

3.

enzymes - precursors and active digestive forms a. trypsinogen ------> trypsin enterokinase b. procarboxypeptidase --------> trypsin chymotrypsinogen --------> trypsin carboxypeptidase chymotrypsin

c. B.

amylase (carbohydrates), lipases (fats), nucleases (nucleic acids)

Regulation of Pancreatic Secretion 1. 2. 3. parasympathetic causes release during cephalic and gastric phases of gastric secretion secretin - hormone that causes release of "bicarbonate-rich" pancreatic juices in response to the presence of HCl cholecystokinin - hormone that causes release of "enzyme-rich" pancreatic juice in response to the presence of proteins and fats

VI.

Digestive Processes of the Small Intestine A. Optimal Conditions for Digestion & Absorption 1. 2. B. pancreatic juice & bile - enzymes, emulsifying fats, and pH are essential for proper intestinal processes small intestine is PRIMARY site for absorption of nutrients into the cardiovascular system

Movement in the Small Intestine 1. 2. segmentation - longitudinal flow of chyme through the tube (duodenum -> ileum) migrating mobility complex - activity that moves the chyme from the ileum to the cecum through the ileocecal valve

VII.

Digestive Processes of the Large Intestine

A.

Bacterial Flora 1. 2. 3. digest remaining carbohydrates responsible for producing gas (flatus) synthesize & complex B vitamins and vitamin K

B.

Digestion and Absorption 1. 2. reclaim most of the water reclaim some of the electrolytes (Na+ and Cl-)

C.

Motility of the Large Intestine 1. haustral contractions - slow acting segmental motion; moves chyme from one segment to next 2. mass movements - peristaltic waves that move food to the rectum during/after eating a. diverticula - herniation of the mucosa through the wall of the colon (sigmoid colon)

D.

Defecation 1. defecation reflex when feces (stool) enters rectum, spinal cord reflex is triggered a. b. 2. 3. 4. internal sphincter (involuntary) external sphincter (voluntary)

Valsalva's maneuver - contraction of diaphragm and abdominal muscles to increase pressure for defecation diarrhea - too much water in the stool constipation - insufficient water or fiber

VIII.

Chemical Digestion A. Enzymatic Hydrolysis ("water" "breaking") 1. hydrolysis - a water molecule is added between two "monomers" of a complex organic molecule in order break it down into its component parts

B.

Carbohydrate Digestion

1. 2. 3. 4.

5. C.

monosaccharides - "monomers" such as glucose, fructose, and galactose disaccharides - sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar) polysaccharides - starch (grains), glycogen (muscle) 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 lactose intolerance - decreased ability to digest lactose in the diet (use "lactase" supplements)

Protein Digestion 1. 2. 3. a. amino acids - the "monomer" components of protein stomach - pepsinogen --------> pepsin (low pH) small intestine enzymes that cleave throughout the protein trypsinogen ----------> chymotrypsinogen -----> b. c. trypsin chymotrypsin

carboxypeptidase (carboxyl end of protein) aminopeptidase, dipeptidase (amino end)

D.

Lipid (Fat) Digestion 1. 2. 3. lipid structure - glycerol + 3 triglycerides lipases - enzymes that break down lipids bile salts - "emulsify" fats in 1 micron "micelles"

E.

Nucleic Acid Digestion 1. pancreatic nucleases - break down DNA and RNA

IX.

Absorption of Nutrients A. General Features 1. transepithelial transport - nutrients must pass across the epithelial lining of the small intestine

2. B.

active transport - most nutrients must be transported across membrane using ATP of the cells

Carbohydrate Absorption 1. facilitated diffusion - glucose and galactose (coupled with active transport of Na+) a. "carrier molecule" has binding sites for both sugar and Na+; relies on Na+ gradient

C.

Protein (Amino Acid) Absorption 1. facilitated diffusion - amino acids and small peptides (coupled with Na+ active transport) a. "carrier molecule" has binding sites for both amino acid and Na+; relies on Na+ gradient 2. food allergies - absorption of proteins in infant gut causes early immune reaction

D.

Lipid Absorption 1. micelles - tiny balls of fats that result from bile salt emulsification and "lecithin" a. b. c. contain cholesterol and fat-soluble vitamins diffuse through lipid bilayer of membrane chylomicrons - micelles combined with associated proteins within the cell; enter the lacteals of the lymphatic system

E.

Nucleic Acid Absorption 1. pentoses, nitrogen bases, phosphates - absorbed by similar processes as sugars and amino acids

F.

Vitamin Absorption 1. fat soluble - Vitamins A, D, E, K are absorbed by epithelial cells along with lipid micelles a. OLESTRA - will carry fat-soluble vitamins out in feces with it water soluble - Vitamins B & C absorbed by diffusion

2.

3. G.

Vitamin B12 - large and electrically charged, must bind with "intrinsic factor" before being taken into the cell by endocytosis

Electrolyte Absorption 1. Fe and Ca - primarily absorbed in small intestine a. b. c. 2. 3. 4. ferritin - sequesters Fe in intestinal cells transferrin - transfers Fe into circulation when need is present (menstruation) Vitamin D - facilitates Ca absorption

Na - exchanged for sugars and amino acids Cl - absorbed into cells and exchanged for HCO3K - absorbed into cells due to osmotic gradients

H.

Water Absorption 1. 2. small intestine - 95% of water absorbed by small intestine following transport of solutes large intestine - absorbs remaining water before moving the chyme on to the rectum

I.

Malabsorption of Nutrients 1. 2. 3. impairment of bile or pancreatic juice release infections of the intestinal mucosa gluten enteropathy - "gluten" protein in grains damages the mucosa of the intestines Lecture Notes: Immune System (Part II: Adaptive Immune System)

THIS IS THE FIRST PART OF A LECTURE ON THE ADAPTIVE IMMUNE SYSTEM ANOTHER PART OF TO THIS LECTURE WILL FOLLOW! I. Adaptive or Specific Immune System A. General Characteristics 1. Specific so that it can eliminate with equal precision almost any type of pathogen 2. Functional System a. can eliminate specific foreign substances as well as abnormal body cells b. can magnify the inflammatory response

3. B. a. History 1.

i. responsible for most complement activation Must be primed by an initial exposure to a specific foreign substance called an antigen takes time

II.

experiments in the late 1800s found that there were protective factors in the blood that defended against future infection by the same pathogen a. protective factors are proteins called antibodies b. these factors could be transferred to other organisms that were not exposed to the antigen 2. important findings about the adaptive immune response a. antigen-specific b. systemic c. has “memory” C. Two branches of adaptive immunity 1. Humoral immunity or antibody-mediated immunity consists of antibodies circulating in the fluids of the body a. produced by lymphocytes or their offspring 2. Cellular or cell-mediated immunity – lymphocytes themselves a. Targets – virus or parasite-infected tissue cells, cancer cells, foreign graft cells b. can act directly by lysing foreign cells or indirectly by releasing chemicals that enhance the inflammatory response or activate other lymphocytes or macrophages. Antigens A. Antigens vs. Haptens 1. Antigens – substances that can mobilize the immune system and provoke an immune response a. most large, complex molecules that are NOT normally present in the body b. help distinguish “self” from “nonself” 2. Complete antigens a. have immunogenicity – the ability to stimulate formation of specific lymphocytes and antibody production b. have reactivity – the ability to react with the lymphocytes and antibodies c. antigens include nearly all foreign proteins, nucleic acids, lipids, and many large polysaccharides. i. proteins are the strongest antigens d. other antigens can be pollen grains or microorganisms e. generally small molecules like peptides, nucleotides, and many hormones are NOT immunogenic f. these small particles can link with other substances though and become immunogenic

III.

i. allergies 3. Haptens – small molecules that are reactive but not immunogenic unless attached to a protein carrier B. Antigenic Determinants 1. only certain parts of an antigen is immunogenic. This part is known as the antigenic determinant 2. free antibodies or activated lymphocytes bind to these antigenic determinants 3. a single antigen can have a variety of antigenic determinants and stimulate many different kinds of antibodies 4. large simple molecules that have many regularly repeating units (not chemically complex) are not very immunogenic. C. Self-antigens: MHC proteins 1. self-antigens – not foreign to us, but is foreign to other individuals 2. MHC proteins (major histocompatibility complex) – group of glycoproteins that marks a cell as self a. millions of different combinations of the genes are possible, it is unlikely that anybody except for identical twins will have the same MHC proteins b. Class I MHC proteins are found on virtually all body cells c. Class II MHC proteins are found only on certain cells that act in the immune response Cells of the Adaptive Immune System A. Types 1. B-cells - involved in the humoral immunity 2. T-cells – involved in cell-mediated immunity 3. APC (antigen presenting cells) – does not respond to specific antigens, but plays an auxillary role B. Lymphocytes 1. originate from hematopoietic stem cells in red bone marrow 2. immature lymphocytes are identical when released from bone marrow a. determination of which lymphocyte (B or T) depends on where in the body it becomes immunocompetent i. immunocompetent - able to recognize a specific antigen by binding to it 3. T cells formed in the thymus (2-3 days) where the T cells are selected for their ability to identify foreign antigens a. negative selection – lymphocytes that strongly attack selfantigens are destroyed in the thymic medulla b. positive selection – weakly anti-self continue to develop and the ones that can best recognize self when attached to antigens are identified. This occurs in the thymic cortex. c. lymphocytes develop self-tolerance and

C.

immunocompetence 4. B cells become immunocompetent and self-tolerant in bone marrow a. anergy – self-reactive B cells are inactivated 5. primary lymphoid organs – thymus and bone marrow 6. secondary lymphoid organs – all other lymphoid organs 7. immunocompetent lymphocytes display receptors that bind to specific antigens a. cells are committed because all of their 10-100 thousand receptors are identical 8. Lymphocytes become immunocompetent before meeting the antigens they may later attack – genes determine which specific foreign substances our immune system will be able to recognize and resist 9. immature lymphocytes that are immunocompetent go to lymph nodes, spleen, and other secondary lymphoid organs where encounters with antigens occur and they become fully functional B and T cells. Antigen-Presenting Cells (APCs) 1. engulfs particles and presents fragments of these antigens on their own surfaces where they can be recognized by T cells. a. major types are: dendritic cells (interstitial cells of connective tissues and Langerhans’ cells of the skin epidermis), macrophages, and activated B lymphocytes 2. APCs secrete proteins that activate T cells and activated T cells secrete chemicals that activate macrophages and increase DC maturation. 3. APCs and lymphocytes are found throughout the lymphatic system but T cells are more numerous in paracortical areas of lymph nodes and DC and B cells are more numerous in germinal centers of lymph nodes 4. Macrophages tend to remain fixed in lymphoid organs 5. Lymphocytes circulate continuously throughout the body (especially T cells – 65-85% of bloodborne lymphocytes)

Lecture Notes: Immune System (Part II: Adaptive Immune System) THIS IS THE SECOND PART OF THE ADAPTIVE IMMUNE SYSTEM LECTURE! IV. Humoral Immune Response A. Clonal Selection and differentiation of B Cells 1. antigen challenge – the first encounter between an immunocompetent lymphocyte and an invading antigen. 2. immunocompent B cells are activated by antigen binding to receptors on the B cell surface  cross-linked adjacent antigen-receptor complexes are internalized by endocytosis  Clonal selection is triggered  B cells grow and multiply to form an army of exact replicas called clones  Clones become either plasma cells or memory B cells  Plasma cells secrete antibodies  Memory B cells  can mount an almost immediate attack if the same antigen is encountered again 3. Plasma cells can secrete antibodies at a rate of about 2000 molecules/sec and have a life span of 4 to 5 days. 4. Memory cells are long-lived 5. Primary immune response – cellular proliferation and differentiation upon initial exposure to antigen a. lasts 3-6 days with peak plasma antibody levels reached at about 10 days 6. Secondary immune response – reexposure to the same antigen a. faster and more prolonged than primary immune response b. due to the immunological memory of sensitized memory B cells c. takes 2-3 days to reach antibody levels that EXCEED those of primary immune response d. antibodies bind with greater affinity and blood levels remain high for weeks to months e. some memory cells can last a lifetime B. Active and Passive Humoral Immunity 1. active humoral immunity – when B cells encounter antigens and produce antibodies against them a. naturally acquired – obtained by exposure to bacterial and viral infections b. artificially acquired – obtained from vaccines i. vaccines contain dead or attenuated (living but extremely weakened) pathogens or parts of them ii. vaccines can spare us most of the discomfort from a primary response and provide functional antigenic

2. a. b. c. C. Antibodies 1. a. 2. a. b. c. d. e. f. g. h.

determinants that are immunogenic and reactive iii. booster shots – intensify the immune response iv. wiped out smallpox and decreased illnesses like whooping cough, polio, and measles as well as hepatitis B, tetanus, and pneumonia v. vaccines target helper T cells (TH2 cells) but not TH1 cells which provide strong cellular responses so lots of antibodies are formed but cellular immunological memory is poorly established vi. in some cases can cause disease if the antigen isn’t weakened enough or cause allergies vii. “naked DNA” antiviral vaccines and edible vaccines help prevent allergic responses passive humoral immunity – antibodies are harvested from the serum of an immune human or animal donor. immunological memory does not occur so immunity ends when the “borrowed” antibodies naturally degrade in the body. passive immunity can be conferred naturally from a mother to a fetus and the mother’s antibodies can protect the baby for several months artificial passive immunity can come from sera such as gamma globulin (administered after hepatitis exposure) or antivenoms or antitoxins antibodies are also called immunoglobulins Igs are gamma globulin part of blood proteins antibody structure made of 4 looping polypeptide chains linked together by disulfide bonds 2 chains are identical and are called heavy (H) chains and are made up of about 400 amino acids each the other 2 are also identical to each other and are called light (L) chains but are only about half the size of the heavy chains hinge region is at the approximate middle where two disulfide bonds connect the two heavy chains all four chains together form a molecule called an antibody monomer and is roughly T or Y shaped variable region are at the ends of the H and L chains and together form the antigen binding site constant regions form the stem of the monomer and determine the antibody class constant regions are the effector regions and dictate which cells and chemicals the antibody can bind to and how the antibody class will function in antigen elimination.

i. 3. a. b.

c.

d.

e.

4. a.

b.

c.

E.g. antibodies can fix complement, circulate in the blood, can be found in body secretions, cross the placental barrier, etc. antibody classes IgD – exists as a monomer and is attached to the external surface of the B cell where it functions as an antigen receptor and is important in B cell activation IgM – exists in a monomer or pentamer form. i. monomer attached to the B cell surface and is an antigen receptor ii. pentamer circulates in blood plasma and is released by plasma cells during the primary response. It presence in the blood indicates current infection and it acts as a potent agglutinating agent and readily fixes and activates complement IgG –exists as a monomer and is the most abundant and diverse antibody in plasma and accounts for 75-85% of circulating antibodies. Can protect against bacteria, viruses, and toxins and can fix complement. It is the main antibody of both primary and secondary responses. IgA – is a dimer in plasma and is also called secretory IgA because it is present in body secretions such as saliva, sweat, intestinal juice, and milk and helps prevent pathogens from gaining access to the body. IgE – a monomer that is secreted by epithelial plasma cells and almost never found in the blood. They bind to mast cells and basophils when activated by antigen and it causes those cells to release histamine and other chemicals that mediate inflammation and allergic reactions. Blood IgE levels rise dramatically during allergic reactions or chronic gastrointestinal tract parasites. antibody diversity plasma cells can make over a billion types of antibodies due to resuffuling of gene segments in a process called somatic recombination. Gene segments recombine as B cells become immunocompetent and the newly assembled genes become expressed in the surface receptors of B cells and are later released by plasma cells as antibodies. Random mixes of H and L gene segments plus extremely variable regions of the variable gene segments called hypervariable regions create the huge variability seen in antibodies. Plasma cells can secrete 2 or more different antibody classes with the same antigen specificity. i. Primary response starts with IgM release by a plasma cell followed by secretion of IgG by the

V.

same plasma cell. ii. Secondary responses consist almost entirely of IgG release. 5. antibody targets and functions a. antibodies inactivate antigen-bearing invaders and tag them for destruction b. common event is antigen-antibody complexes c. defensive mechanisms i. complement fixation and activation – chief weapon against cellular antigens. Antibodies bind to cells, change shape on constant regions and allow complement fixation onto the antigenic cell surface causing the cell to lyse. Also starts a positive feedback loop enhancing inflammatory response and promoting phagocytosis via opsonization. ii. neutralization – antibodies bind to specific sites on the antigen preventing them from binding to their cellular targets and causing injury. iii. agglutination – cross-linking of many antigenantibody complexes as to cause clumping iv. precipitation – soluble molecules are cross-linked into large complexes and settle out of solution where they are easily captured and consumed by phagocytes 6. monoclonal antibodies – commercially available pure antibody preparations specific for a single antigenic determinant produced by descendents of a single cell a. made from hybridomas which are fusions of tumor cells and B lymphocytes and have good characteristics of each like the ability to proliferate indefinitely in culture and can produce a single type of antibody. i. can be used to diagnose pregnancy, some sexually transmitted diseases, some types of cancer, hepatitis, and rabies ii. can treat leukemia and lymphomas by specifically delivering anticancer drugs. Cell-Mediated Immune Response A. Types of T cells 1. CD4 cells have the glycoprotein CD4 cell surface receptors displayed a. also called T4 cells, CD4 cells are primarily helper T cells (TH) 2. CD8 cells have the glycoprotein CD8 cell surface receptors displayed a. also called T8 cells, CD8 cells are primarily cytotoxic T cells (TC)

B.

C.

Delayed hypersensitive T cells (TDH) a special type of TH cell 4. Suppressor T cells (TS) 5. Memory T cells Functions of T cells 1. T cells can recognize and respond only to processed fragments of protein antigen displayed on the surface of cells 2. More effective in cell-cell interactions unlike antibodies, which cannot attack microorganisms that can quickly slip inside body cells and multiply like tuberculosis bacillus. 3. TH cells binds with specific antigens presented by an APC and stimulates production of other cells like TC cells and B cells. It can also act directly by secreting cytokines like interleukins 2, 4, and 5. 4. TC cells, also called cytolytic (CTL) or killer T cells, are activated by an antigen presented by any body cell and are recruited by TH cells. TH cells also enhance the activity of TC cells. TC cells specialize in killing virus-invaded body cells and cancer cells and is involved with rejection of foreign tissue graphs. Secretes lymphotoxin, which causes DNA fragmentation and promotes inflammation. Also secretes perforin which causes cell lysis by creating large pores in the membrane of target cells. 5. TS cells stops activity of B and T cells once infection has been conquered. Secretes suppressor factors which suppresses the immune response. 6. TDH promotes nonspecific killing by macrophages and is important in delayed hypersensitivity reactions like allergic contact dermatitis which follows skin contact with poison ivy, heavy metals, etc. 7. Memory T cells are like the memory B cells in the fact that they are generated during the primary response and may exist in the body for years allowing rapid response to subsequent reinfections of the same antigen. Clonal selection and differentiation of T cells 1. T cell cloning requires “double recognition” such that immunocompetent T cells must be able to simultaneous recognize the antigen and a MHC protein. a. Class I MHC proteins are displayed by all body cells except for red blood cells and are always recognized by CD8 T cells. Class I MHC proteins are made in the ER where endogenous antigens, foreign proteins that are synthesized within a body cell as from viral activity or cancerous cells, are transported by special transport

3.

VI.

proteins called TAPs. The antigen is then loaded onto the Class I MHC protein where the complex (MHC + antigen) is incorporated into the plasma membrane. b. Class II MHC proteins are displayed on the surfaces of mature B cells, some T cells, and antigen-presenting cells, where they enable the cells of the immune system to recognize one another. They are synthesized in the ER but unlike MHC proteins they have an invariant chain attached which prevents MHC Class II binding to peptides in the ER. The MHC Class II protein migrates to the phagolysosome where the invariant chain is removed and exogenous antigens, which are foreign antigens that have been phagocytosed and broken down within the phagosome vesicle, are loaded. The loaded MHC Class II proteins are then displayed on the cell surface where CD4 cells can recognize them. 2. T cell activation a. involves two steps: antigen binding and costimulation. i. Antigen binding - T cell receptors or TCRs bind to an antigen-MHC protein complex on the surface of the body cell. 1. MHC restriction – preference for certain classes of MHC proteins 2. immunologic surveillance – the process in which T cells adhere to and crawl over other cells in search of antigens that they might recognize ii. Costimulation – the process of a T cell recognizing a costimulatory signal before it can proliferate to form a clone. The costimulatory signal could be a T cell binding to other surface receptors on an APC like the B7 protein of macrophages binding to the CD28 T cell receptor. Other costimulatory signals could be cytokines like interleukin 1 and 2. Costimulation is REQUIRED for T cell cloning. Organ Transplants and Prevention of Rejection A. Types of Grafts 1. Autografts – tissue grafts transplanted from one body site to another in the same person 2. isografts – grafts donated by genetically identical individuals 3. allografts – grafts transplanted from individuals that are not genetically identical but belong to the same species. 4. Xenografts – grafts taken from another animal species B. Procedures 1. to minimize rejection patients receiving grafts are treated

VII.

with immunosuppressive theraphy involving 1 or more of: a. corticosteriod drugs like prednisone to suppress inflammation b. cytotoxic drugs c. radiation therapy d. antilymphocyte globulins e. an immunosuppressant drug such as cyclosporin f. all have severe side effects Homeostatic Imbalances of Immunity A. Immunodeficiencies 1. immunodeficiencies – congenital and acquired conditions in which the production or function of immune cells, phagocytes, or complement is abnormal. a. severe combined immunodeficiency (SCID) syndrome results from genetic defects that produce a B and T cell deficiency. b. Hodgkin’s disease, cancer of the lymph nodes, is an acquired immunodeficiency c. AIDS (acquired immune deficiency syndrome) – interferes with the activity of helper T (CD4) cells. Caused by the virus HIV (human immunodeficiency virus) which destroys the helper T cells. After invading the cells with a coat glycoprotein gp120 with the help of gp41, HIV uses the enzyme reverse transcriptase to make DNA from its viral RNA. The DNA copy, called a provirus, then inserts into the host DNA and directs the synthesis of more HIV cells. AIDS is treated by reverse transcriptase inhibitors like AZT and protease inhibitors like saquinavir, etc. Combination therapy seemed to be very effective but as of late it is failing in about half the treated patients. B. Autoimmune disease 1. autoimmune disease – condition that results when the body produces antibodies and sensitized cytotoxic T cells that destroy its own tissues. a. Multiple sclerosis (MS) – destroys the white matter of the brain and spinal cord b. Myasthenia gravis – impairs communication between nerves and skeletal muscle c. Graves’ disease – prompts the thyroid gland to produce excessive amounts of thyroxine d. Type I diabetes mellitus – destroys pancreatic beta cells resulting in a deficit of insulin and the inability to use carbohydrates e. systemic lupus erythematosus (SLE) – systemic disease that affects the kidneys, heart, lungs, and skin. f. Glomerulonephritis – severe impairment of renal function

C.

rheumatoid arthritis (RA) – systematically destroys joints can be treated by depressing immune response like antibodies to the CD4 receptor on TH cells and thalidomide, which inhibits production of TNF-α ., which is tumor necrosis factor that produced by lymphocytes and in large amounts by macrophages that enhances nonspecific killing, slows tumor growth, causes selective damage to blood vessels, enhance granulocyte chemotaxis, and help activate T cells, phagocytes, and eosinophils. 2. Possible triggers for autoimmune disorders a. lymphocyte programming is ineffective (negative selection ineffective) b. new self-antigens appear c. foreign antigens resemble self-antigens i. antibodies against streptococcal infection can crossreact with heart antigens causing rheumatic fever which causes lasting damage to heart muscle, valves, joints, and kidneys. Hypersensitivities 1. hypersensitivities or allergies – result of immune responses in which the immune system causes tissue damage as it fights off a perceived “threat” a. antigens are called allergens; rarely lethal b. types of hypersensitivities are determined by their time course and whether T cells are the principal immune elements involved. c. antibody-mediated hypersensitivity (immediate, acute, or type I hypersensitivities) begin within seconds of contact and can last ½ hour. i. anaphylaxis – most common type of immediate hypersensitivity where allergens trigger release of IL-4 which in turn stimulates production of IgEsecreting plasma cells which attach to mast cells and basophils which release histamine and other inflammatory chemicals upon further exposure to the allergen. Treated with antihistamines ii. anaphylactic shock – rare but is basically systemic anaphylaxis where bronchioles constrict, edema occurs, and circulatory shock may occur resulting in death within minutes. Treated with epinephrine. iii. atopy – spontaneous development of immediatetype allergies to certain environmental antigens. May result in hives, hay fever, or asthmatic symptoms. d. antibody-mediated hypersensitivity (subacute hypersensitivities) – slower onset 1-3 hours and longer

g. h.

duration 10-15 hours i. cytotoxic (type II) reactions – antibodies bind to antigens on specific body cells to stimulate phagocytosis and complement-mediated lysis of cellular antigens. E.g. mismatched blood transfusions ii. immune complex (type III) reactions – antigenantibody complexes form that cannot be cleared. Intense inflammatory reactions occur and severe damage to local tissues. E.g. farmer’s lung e. delayed hypersensitivity (type IV) reactions are cellmediated and appear 1-3 days after exposure to the allergen. i. involves cytotoxic cells and TDH cells. Corticosteroid drugs are used for treatment. 1. includes allergic contact dermatitis and TB skin tests 2. provides protective reactions against viruses, bacteria, fungi, protozoa, resistance against cancer, rejection of foreign grafts or transplanted organs, and protection against facultative intracellular pathogens (FIPs) like salmonella bacteria. Lecture Notes: Immune System (Part I: Innate Immune System) I. Parts of the Immune System A. Innate or Nonspecific system 1. External body membranes like skin and mucosae 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

II. Innate defenses A. Function 1. combat pathogens which are harmful or disease-causing microorganisms 2. in a state of readiness and responds to protect the body from ALL foreign substances starting within minutes of invasion. B. Surface Barriers 1. Skin i. heavily keratinized epithelial membrane is a physical barrier ii. resistant to most weak acids, weak bases, bacterial enzymes and toxins. iii. secretions are acidic (pH 3-5) and inhibit bacterial growth iv. sebum contains chemicals that are toxic to bacteria 2. Mucous membranes i. line all body cavities that open to the exterior including the digestive, respiratory, urinary, and reproductive tracts. ii. stomach secretes HCl and protein-digesting enzymes which kill microorganisms. iii. Saliva and lacrimal fluid contains lysozyme, an enzyme that destroys bacteria. iv. Sticky mucus traps microorganism that enter the digestive and respiratory passageways. v. structure modifications such as the tiny mucus-coated hairs and ciliated mucosa of the respiratory tract which trap and sweep particles away from lower respiratory passages. 3. When surface barriers are breached by small nicks or cuts then the microorganisms invade deeper tissues and the internal innate defenses are important 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.

like

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 antibioticchemicals. 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 I. The Mechanics of Breathing A. Relationships of Pressure 1. 2. 3. atmospheric air pressure 760 mm Hg (at sea level) negative air pressure - LESS than 760 mm Hg positive air pressure - MORE than 760 mm Hg

4. 5.

intrapleural pressure - pressure within the pleural "balloon" which surrounds the lung intrapulmonary pressure - pressure within the alveoli (tiny sacs) of the lung itself

Factors holding lungs AGAINST the thorax wall: 1. 2. 3. Surface tension holding the "visceral" and "parietal" pleura together Intrapulmonary pressure ALWAYS slightly greater than intrapleural pressure by 4 mm Hg Atmospheric pressure acting on the lungs a. b. atelectasis (collapsed lung) - hole in pleural "balloon" causes equalization of pressure and collapse of the lung pneumothorax - abnormal air in the intrapleural space, can lead to collapsed lung

Factors facilitating lung movement AWAY from thorax wall: 1. 2. II. Elasticity of lungs allows them to assume smallest shape for given pressure conditions Fluid film on alveoli allows them to assume smallest shape for given pressure conditions

Volume/Pressure & Inspiration/Expiration A. Boyle's Law on Volume/Pressure Relationships 1. Volume is INVERSELY proportional to Pressure a. b. INCREASE in Volume -> DECREASE in Pressure DECREASE in Volume -> INCREASE in Pressure

VOLUME change --> PRESSURE change gas flows to equalize the pressure 2. B. Simple Example of Boyle's Law plastic bag with plastic tube in the top as bag expands by pulling, gas moves IN as bag shrinks by squashing, gas moves OUT

Inspiration

1. 2. 3.

diaphragm muscle contracts, increasing thoracic cavity size in the superior-inferior dimension external intercostal muscles contract, expanding lateral & anteriorposterior dimension INCREASED volume (about 0.5 liter) DECREASED pulmonary pressure (-1 mm Hg) air rushes into lungs to fill alveoli deep/forced inspirations - as during exercise and pulmonary disease scalenes, sternocleidomastoid, pectorals are used for more volume expansion of thorax

4. * C.

Expiration 1. quiet expiration (exhalation) - simple elasticity of the lungs DECREASES volume INCREASED pulmonary pressure -> movement of air out of the lungs forced expiration - contraction of abdominal wall muscles (i.e. obliques & transversus abdominus) further DECREASES volume beyond relaxed point ----> further INCREASE in pulmonary pressure ---> more air moves out

2.

III.

Factors Influencing Pulmonary Ventilation A. Respiratory Passageway Resistance 1. upper respiratory passageways - relatively large, very little resistance to airflow (unless obstruction such as from food lodging or cancer) lower respiratory passageways - from medium-sized bronchioles on down, can alter diameter based on autonomic stimulation a. b. parasympathetic - causes bronchioconstriction sympathetic - inhibits bronchioconstriction

2.

epinephrine - used to treat life-threatening bronchioconstriction such as during asthma and anaphylactic shock (carried by people susceptible to sudden constriction) B. Lung Compliance & Elasticity

1. a. b. c. d. 2.

lung compliance - the ease with which lungs can be expanded by muscle contraction of thorax fibrosis - decreases compliance blocked bronchi - decreases compliance surface tension - alveoli difficult to expand thorax inflexibility - decreases compliance lung elasticity - the ease with which lungs can contract to their normal resting size (exhalation) a. emphysema - decreases elasticity alveolar surface tension - liquid on surface of alveoli causes them to collapse to smallest size a. b. surfactant - lipoproteins that reduces surface tension on alveoli, allowing them to expand more easily infant respiratory distress syndrome - premature babies that do not yet produce enough surfactant; must be ventilated for respiration

3.

IV.

Volumes, Capacities, and Function Tests A. Respiratory VOLUMES (20 yr old healthy male, 155 lbs.) 1. 2. 3. 4. B. tidal volume (TV) - normal volume moving in/out (0.5 L) inspiratory reserve volume (IRV) - volume inhaled AFTER normal tidal volume when asked to take deepest possible breath (2.1-3.2 L) expiratory reserve volume (ERV) - volume exhaled AFTER normal tidal volume when asked to force out all air possible (1.2.0 L) residual volume (RV) - air that remains in lungs even after totally forced exhalation (1.2 L)

Respiratory CAPACITIES 1. 2. 3. 4. inspiratory capacity (IC) = TV + IRV (MAXIMUM volume of air that can be inhaled) functional residual capacity (FRC) ERV + RV (all non-tidal volume expiration) vital capacity (VC) = TV + IRV + ERV (TOTAL volume of air that can be moved) total lung capacity (TLC) = TV + IRV + ERV + RV (the SUM of all volumes; about 6.0 L)

D.

Dead Space 1. 2. 3. anatomical dead space - all areas where gas exchange does not occur (all but alveoli) alveolar dead space - non-functional alveoli total dead space - anatomical + alveolar

E.

Pulmonary Function Tests 1. spirometer - measures volume changes during breathing a. b. 2. 3. 4. obstructive pulmonary disease - increased resistance to air flow (bronchitis or asthma) restrictive disorders - decrease in Total Lung Capacity (TB or polio)

minute respiratory volume (MRV) - total volume flowing in & out in 1 minute (resting rate = 6 L per minute) forced vital capacity (FVC) - total volume exhaled after forceful exhalation of a deep breath forced expiratory volume (FEV) - FEV volume measured in 1 second intervals (FEV1...)

F.

Alveolar Retention Rate (AVR) AVR (NORMAL) AVR (NORMAL) AVR = breath rate X = 12/minute X = 4.2 L/min (TV - dead space) (500 ml – 150 ml)

V.

Basic Properties of Gases A. Dalton's Law of Partial Pressures 1. partial pressure - the "part" of the total air pressure caused by one component of a gas Gas Pressure (P) ALL AIR Nitrogen X 760) Percent 100.0% 78.6% Partial 760 mm Hg 597 mm Hg (0.79

Oxygen 20.9% X 760) Carbon Dioxide 0.04% (0.0004 X 760) 2. 3. B.

l59 mm Hg 0.3 mm Hg

(0.21

altitude - air pressure @ 10,000 ft = 563 mm Hg scuba diving - air pressure @ 100 ft = 3000 mm Hg

Henry's Law of Gas Diffusion into Liquid 1. 2. Henry's Law - a certain gas will diffuse INTO or OUT OF a liquid down its concentration gradient in proportion to its partial pressure solubility - the ease with which a certain gas will "dissolve" into a liquid (like blood plasma) Carbon Dioxide Oxygen Nitrogen

HIGHest solubility in plasma LOWest solubility in plasma C.

Hyperbaric (Above normal pressure) Conditions 1. 2. 3. Creates HIGH gradient for gas entry into the body therapeutic - oxygen forced into blood during: carbon monoxide poisoning, circulatory shock, asphyxiation, gangrene, tetanus, etc. 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

VI.

Gas Exchange: Lungs, Blood, Tissues A. External Respiration (Air & Lungs) 1. Partial Pressure Gradients & Solubilities a. b. Oxygen: alveolar (104 mm) ---> blood (40 mm) Carbon Dioxide: blood (45 mm) ----> alveolar (40 mm) (carbon dioxide much more soluble than oxygen)

2. Alveolar Membrane Thickness (0.5-1.0 micron) a. b. very easy for gas to diffuse across alveoli edema - increases thickness, decreases diffusion

3.

Total Alveolar Surface Area for Exchange a. b. total surface area healthy lung = 145 sq. Meters emphysema - decreases total alveolar surface area

4.

Ventilation-Blood Flow Coupling a. b. c. d. low Oxygen in alveolus -> vasoconstriction high Oxygen in alveolus -> vasodilation high Carb Diox in alveolus -> dilate bronchioles low Carb Diox in alveolus -> constrict bronchioles

B.

Internal Respiration (Blood & Tissues) 1. 2. Oxygen: blood (104 mm) -> tissues (40 mm) Carbon Dioxide: tissues (>45 mm) -> blood (40 mm)

VII.

Oxygen Transport in Blood: Hemoglobin A. Association & Dissociation of Oxygen + Hemoglobin 1. 2. oxyhemoglobin (HbO2) - oxygen molecule bound deoxyhemoglobin (HHb) - oxygen unbound H-Hb + 3. 4. 5. O2 <= === => HbO2 + H+

binding gets more efficient as each O2 binds release gets easier as each O2 is released Several factors regulate AFFINITY of O2 a. b. c. d. Partial Pressure of O2 temperature blood pH (acidity) concentration of “diphosphoglycerate” (DPG)

B.

Effects of Partial Pressure of O2 1. oxygen-hemoglobin dissociation curve a. b. c. d. 104 mm (lungs) - 100% saturation (20 ml/100 ml) 40 mm (tissues) - 75% saturation (15 ml/100 ml) right shift - Decreased Affinity, more O2 unloaded left shift- Increased Affinity, less O2 unloaded

C.

Effects of Temperature 1. 2. HIGHER Temperature LOWER Temperature --> Decreased Affinity (right) --> Increased Affinity (left)

D.

Effects of pH (Acidity) 1. 2. HIGHER pH --> Increased Affinity (left) LOWER pH --> Decreased Affinity (right) "Bohr Effect" a. more Carbon Dioxide, lower pH (more H+), more O2 release

E.

Effects of Diphosphoglycerate (DPG) 1. 2. 3. DPG - produced by anaerobic processes in RBCs HIGHER DPG > Decreased Affinity (right) thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.

Oxygen Transport Problems 1. hypoxia - below normal delivery of Oxygen a. b. c. 2. anemic hypoxia - low RBC or hemoglobin stagnant hypoxia - impaired/blocked blood flow hypoxemic hypoxia - poor lung gas exchange

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

VIII. Transport of Carbon Dioxide A. B. Dissolved in Blood Plasma (7-10%) Bound to Hemoglobin (20-30%) 1. 2. carbaminohemoglobin - Carb Diox binds to an amino acid on the polypeptide chains Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry a. tissues - as Ox is unloaded, affinity for Carb Diox increases

b. C.

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

Bicarbonate Ion Form in Plasma (60-70%) 1. Carbon Dioxide combines with water to form Bicarbonate

CO2 + H2O <==> H2CO3 <==> H+ + HCO32. carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions a. b. 3. tissues - catalyzes formation of Bicarbonate lungs - catalyzes formation of Carb Diox

Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Ox to tissues a. since hemoglobin "buffers" to H+, the actual pH of blood does not change much

4.

Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.

Carbon Dioxide Effects on Blood pH 1. carbonic acid-bicarbonate buffer system --> HCO3- binds to H+ --> H2CO3 releases H+ --> HIGH Carb Diox --> LOW pH (higher --> LOW Carb Diox --> HIGH pH (lower

low pH high pH 2. 3. IX.

low shallow breaths H+) rapid deep breaths H+)

Neural Substrates of Breathing A. Medulla Respiratory Centers

Inspiratory Center (Dorsal Resp Group - rhythmic breathing) ----> phrenic nerve ----> intercostal nerves ----> diaphragm + external intercostals

Expiratory Center (Ventral Resp Group - forced expiration) ----> phrenic nerve ----> intercostal nerves ----> internal intercostals + abdominals (expiration) 1. 2. B. eupnea - normal resting breath rate (12/minute) drug overdose - causes suppression of Inspiratory Center

Pons Respiratory Centers 1. 2. pneumotaxic center - slightly inhibits medulla, causes shorter, shallower, quicker breaths apneustic center - stimulates the medulla, causes longer, deeper, slower breaths

C.

Control of Breathing Rate & Depth 1. 2. 3. breathing rate - stimulation/inhibition of medulla breathing depth - activation of inspiration muscles Hering-Breuer Reflex - stretch of visceral pleura that lungs have expanded (vagal nerve)

D. E. X.

Hypothalamic Control - emotion + pain to the medulla Cortex Controls (Voluntary Breathing) - can override medulla as during singing and talking

Chemical Controls of Respiration A. Chemoreceptors (CO2, O2, H+) 1. 2. B. central chemoreceptors - located in the medulla peripheral chemoreceptors - large vessels of neck

Carbon Dioxide Effects 1. a powerful chemical regulator of breathing by increasing H+ (lowering pH) a. hypercapnia Carbon Dioxide increases -> Carbonic Acid increases -> pH of CSF decreases (higher H+)> DEPTH & RATE increase (hyperventilation)

b. hypocapnia - abnormally low Carbon Dioxide levels which can be produced by excessive hyperventilation; breathing into paper bag increases blood Carbon Dioxide levels C. Oxygen Effects 1. 2. 3. 4. aortic and carotid bodies - oxygen chemoreceptors slight Ox decrease - modulate Carb Diox receptors large Ox decrease - stimulate increase ventilation hypoxic drive - chronic elevation of Carb Diox (due to disease) causes Oxygen levels to have greater effect on regulation of breathing

D.

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

E.

Overview of Chemical Effects Breathing Effect

Chemical

increased Carbon Dioxide (more H+) increase decreased Carbon Dioxide (less H+) decrease slight decrease in Oxygen large decrease in Oxygen decreased pH (more H+) increased pH (less H+) XI. Exercise and Altitude Effects A. Exercise Effects 1. 2. hyperpnea - increase in DEPTH, not rate steady state - increase in RATE and DEPTH gradually altered to MATCH gas exchange needs a. b. c. conscious awareness of exercise cortex stimulates muscles & respiratory center proprioceptors in muscles, tendons, joints effect CO2 system increase ventilation increase decrease

B.

Altitude Effects 1. acclimatization - physiological adaptation to lower Oxygen content at higher altitude a. body “set-points” for Oxygen and Carb Diox will reset over a period of time

XII.

COPD and Cancer A. Chronic Obstructive Pulmonary Disease (COPD) 1. Common features of COPD a. b. c. d. 2. almost all have smoking history dyspnea - chronic "gasping" for air frequent coughing and infections often leads to respiratory failure

obstructive emphysema - usually results from smoking a. b. c. enlargement & deterioration of alveoli loss of elasticity of the lungs "barrel chest" from bronchiole opening during inhalation & constriction during exhalation

3. B.

chronic bronchitis - mucus/inflammation of mucosa

Lung Cancer 1. 2. 3. 4. squamous cell carcinoma (20-40%) - epithelium of the bronchi and bronchioles adenocarcinoma (25-35%) - cells of bronchiole glands and cells of the alveoli small cell carcinoma (10-20%) - special lymphocyte-like cells of the bronchi 90% of all lung cancers are in people who smoke or have smoked Lecture: Fluid, Electrolyte, Acid/Base Balance

I.

Fluids of the Body A. Fluid Compartments 1. intracellular fluid compartment - within the cells themselves (about 25L or 40% of body weight)

2.

extracellular fluid compartment outside the cells (about 15L or 20% of body weight) a. plasma - fluid portion of the blood (3 L) b. interstitial fluid - fluid bathing all cells and tissues of body (12 L)

Total body water volume = 40L or about 60% of body weight B. Fluid Composition 1. 2. 3. nonelectrolytes - no electrical charge (glucose) electrolytes - dissociate into ions (NaCl) milliequivalents per liter (mEg/L) - measure of number of charges in 1 liter of solution concentration of ion (mg/L) mEq/L = ion atomic weight of ion C. Extracellular vs. Intracellular Fluids 1. 2. D. extracellular - high Na+ and high Clintracellular - low Na+ and low Clx # charges per

Fluid Movement between Compartments 1. 2. 3. 4. plasma -> interstitial -> plasma & lymphatics Oxygen, glucose -> into cells Carbon Dioxide, nitrogenous wastes-> out of cells ECF <====> ICF depends on NaCl in the ECF

II.

Water Balance A. Overview of Water Balance 1. 2. 3. B. intake - 90% ingested water; 10% metabolic water output - 60% urine; 28% lungs/skin (mucosa); 12% sweat/feces water need - trigger thirst & release of ADH

The Thirst Mechanism decrease in plasma volume OR increase in osmolarity  excitation of hypothalamic thirst center 

sensation of thirst C. Regulation of Water Output 1. 2. D. obligatory water loss - lungs, sweat, feces regulation of water - kidneys (ADH -> Na+)

Disorders of Water Balance 1. 2. 3. dehydration - water loss -> water intake a. bleeding, burns, sweating, diuretics hypotonic hydration - too much water or Na+ edema - accumulation of water in interstitial space

III.

Regulation of Sodium (Na+) Balance A. B. Sodium (Na+) - 90% of solutes in the ECF; most important and prevalent of all electrolytes Aldosterone - released by adrenal cortex (renin-angiotensin) 1. released in response to: a. b. c. 2. decrease in blood pressure decreased osmolality of filtrate sympathetic stimulation of juxtoglomerular cells

function - increase Na+ reabsorption at distal tubule a. water will follow if ADH makes the distal tubule permeable to water

C.

Baroreceptors 1. 2. located in carotid arteries and aorta respond to changes in stretch due to blood pressure a. blood pressure increases  hypothalamic stimulation  sympathetics to kidneys decrease  increased GFR (water removed) blood pressure decreases (same path as above) ----> ----> ----> lower GFR (water retained)

b. D.

Antidiuretic Hormone (ADH)

1. 2.

released from the posterior pituitary responds to osmoreceptors in the hypothalamus a. decrease in osmo of ECF  decreased release of ADH  less permeability of distal tubule to water  more water released into urine increase in osmo of ECF  increased release of ADH  more permeability of distal tubule to water  less water released into urine

b.

E.

Atrial Natriuretic Factor (ANF) 1. 2. released by cell of heart atria under high B.P. reduces blood pressure and blood volume by INHIBITING nearly all events that promote vasoconstriction and Na+/water retention.

F.

Steroid Hormones 1. 2. estrogen - increases resorption of Na+ in distal convoluted tubule glucocorticoids (cortisol) - increases resorption of Na+ in the distal tubules

IV.

Regulation of Potassium (K+) Balance A. Importance of K+ 1. 2. B. K+ is primary CATION (+) within cells K+ abnormalities cause changes in Resting Mem Pot (neurons, cardiac muscle especially)

Renal Control of K+ Levels 1. 2. 3. 10-15% constantly lost in urine most resorption occurs in Proximal Tubule regulation - changing amount SECRETED into urine in the collecting tubules a. b. low K+ ----> less secretion (intercalated cells in collecting tube can reabsorb more) high K+ -----> more secretion

C.

Factors Controlling K+ Secretion 1. 2. 3. tubule cell intracellular K+ level - when low, secrete less; when high, secrete more aldosterone level - K+ secreted: Na+ reabsorbed a. increase aldosterone -> more K+ secretion b. decrease aldosterone -> less K+ secretion + pH - K and H+ compete for antiport with Na+ a. lower pH (high H+) -> less K+ secretion b. higher pH (low H+) -> more K+ secretion

V.

Regulation of Calcium (Ca++) Balance A. Importance of Ca++ 1. 2. bone is the "reservoir" of most Ca++ in the form of Calcium Phosphate (Ca++ with PO4-2) primary physiological roles (already covered): a. b. c. B. at the muscle and neuron synapse essential for blood clotting process very critical in heart rhythms

Ca++ Regulation: Parathyroid Hormone (PTH) & Calcitonin 1. parathyroid hormone (PTH) - chief control when Ca++ begins to DECREASE too low a. b. c. 2. bones - Ca++ and PO4-2 release to blood small intestine - activates Vitamin D which is essential for Ca++ resorption kidneys - Ca++ reabsorbed (but PO4-2 excreted)

calcitonin (thyroid gland) - released when Ca++ begins to INCREASE too high a. inhibits Ca++ release from bone, increases actual formation of Calcium Phosphate in bone Lecture: Biochemistry

I.

Inorganic Compounds A. Water (H2O) - 60-80% of cells 1. heat capacity - ability to store lots of heat

2. heat of vaporization - lots of heat to evaporate 3. polarity/solvency - ability to dissolve reactants i. ii. 4. salts and large macromolecules normally in solution ideal medium for cellular transport

reactivity - essential for many chemical reactions i. hydrolysis - water added to break down molecules

glycogen + H2O  glucose + glucose + glucose +..... ii. dehydration - water removed to synthesize

glucose + glucose + glucose + ...  glycogen + H2O

B. Salts - cations (Na+) and anions (Cl-) other than H+/OH-

1.

salts dissociate in the presence of water (solution)

2.

called electrolytes because they are charged atoms

3.

Examples of Important Salts in Body i. Na+, Cl-, K+, Ca++ - membrane potential on cell ii. Ca++ and PO4 calcium phosphates for bone iii. Fe++, Mg++, Zn+, Cu+ - blood and enzymes 4. Kidneys are essential for water and salt homeostasis

C. Acids and Bases – H+ donors and H+ acceptors 1. Acids - compounds that release H+ in solution and increase H+

i. HCl - hydrochloric acid released in stomach HCl  H+ + Cl-

ii. HC2H3O2 - acetic acid in vinegar

2. Bases - compounds that receive H+ or produce OH- acceptors i. hydroxides - release OH-(hydroxides ions)

NaOH (sodium hydroxide - lye) MgOH (magnesium hydroxide – milk of magnesia) NaOH Na+ + OHOH- + H+  H2O ii. ammonia - nitrogenous waste  urea (urine) NH3 + H+  NH4+ 3. pH - a measure of H+ concentration in a solution H2O  H+ + OHi. molecules dissociate in pure H2O ii. concentration is 1/10,000,000 = l0-7 1 of l07 water H+

iii. pH = -log10[H+] iv. pure water pH = -log10 [l0-7] = 7.0 4. Neutralization - acid and base combine HCl + NaOH  H2O + NaCl 5. Buffers - dampen the fluctuation of pH in the body i. pH of blood serum = 7.35 to 7.45 (slightly basic) ii. strong acids - completely dissociate (HCl) weak acid - partially dissociate (carbonic acid) iii. strong base - dissociate (NaOH) weak base - partially dissociate (bicarbonate) 6. Carbonic Acid - Bicarbonate Buffer System H2CO3  HCO3- + H+ H2CO3  HCO3- + H+ (H+ + Cl-  HCl) ACID

BASE (NaOH  Na+ + OH-) H2CO3  HCO3-Na+ + H+ + OH- (H2O) i. acid condition - reaction goes to the left ii. base condition - reaction goes to the right II. Organic Compounds A. Characteristics of Organic (Carbon containing) Compounds 1. Exceptions: CO (carbon monoxide) C02 (carbon dioxide) C (graphite and diamond) 2. carbon forms 4 covalent bonds (not ions) 3. carbon is relatively electroneutral (not e-neg) 4. carbon easily forms bonds with H, O, N 5. carbon can form single, double, and triple bonds B. Carbohydrates (C - carbo; H - hydr; O - ates) 1. monosaccharide (one sugar) simple sugars

a. can exist in chain or ring form b. 5-carbon sugars i. ribose - in Ribose Nucleic Acid (RNA) ii. deoxyribose - in Deoxyribose N A (DNA) c. 6-carbon sugars i. glucose - main monosaccharide in blood ii. galactose - glucose isomer (OH changes) iii. fructose - glucose isomer 2. disaccharide (two sugar) double sugars a. b. results from dehydration synthesis of 2 monosacs glucose - fructose = sucrose (table sugar) glucose - glucose = maltose (malt sugar) glucose - galactose = lactose (milk sugar)

3. polysaccharide (many sugar) chains of sugars a. starch - long chains of glucose in plants b. glycogen - long chains of glucose in animals i. stored in liver and muscle cells 4. Functions of Carbohydrates a. quick energy - glucose primary fuel to make ATP b. energy storage - glycogen for storage purpose c. structural - glycolipids for cell identity C. Lipids (fats, phospholipids, steroids) neutral fats (triglycerides) - common fats and oils a. composed of glycerol and 3 fatty acid chains i. non-polar fatty acid side chains make them insoluable in water b. different fats = different fatty acid chains c. saturated fats - all single bonds for carbons i. generally solid at room temperature d. unsaturated fats - one/more double bonds ii. generally liquid at room temperature e. functions - insulation, protection, and long term energy storage (more calories/gram) 2. Phospholipids a. glycerol, 2 1.

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 1. Molecular Structure of Proteins a. 20 different amino acids (same in all life) i. amino end (NH2) ii. acid group (COOH) iii.R-group unique for each amino acid b. dehydration synthesis joins amino acids i. called a peptide bond ii. dipeptide - 2 amino acids iii. tripeptide - 3 amino acids iv. polypeptide - many amino acids 2. Levels of Protein Structure

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 4. Enzymes and Enzyme Function a.enzyme - a protein that catalyzes a reaction i. increase the rate of a natural reaction b.cofactor or coenzyme - essential for function i. could be a metal like Fe, Cu, Zn ii. many derived from Vitamins (like Vit B) c.induced fit model - substrate fits into enzyme i. active site - area where substrate fits ii. enzyme lowers activation energy threshold d. sometimes enzymes must be activated to work 5. Denaturation of Proteins a. i disrupting delicate 3-D shape of the protein i. excessive heat (fever)

ii. excessive pH (too acidic or too basic) b. reversible - protein can reassume its shape c. irreversible - protein is permanently damaged i. cooking albumin in egg white d. can disrupt active site and enzyme activity E. Nucleic Acids (DNA & RNA) 1. nucleotide - basic unit forming the DNA & RNA chains a. base - nitrogen containing ring structure i. adenine (A) ii. cytosine (C) iii. guanine (G) iv. thymine (T) in DNA or uracil (U) in RNA b. sugar - pentose (ribose RNA; deoxyribose DNA) c. phosphate group 2. nucleotide attraction by Hydrogen Bonding of bases a. A=T (A=U in RNA) b. C=G 3. DNA forms a double helix 4. genetic code - sequence of nucleotides dictates sequence of amino acids for a protein 5. gene - a sequence of nucleotides of DNA molecule that codes for one protein F. ATP as "Energy Currency" 1. glycogen and lipids = energy in savings bond ($5,000) 2. glucose = energy as a large check ($100) 3. ATP = energy that can actually be spent by cells ($1) a. high energy phospate bonds ATP  ADP + Pi + ENERGY (Breaking bond releases useable energy)

Lecture: Homeostasis

I. Organization of Life A. Structure:Function and Function:Structure 1. Anatomy - study of the structure of cells, tissues, organs, organisms 2. Physiology - study of how cells, tissues, organs, organisms function 3. Darwin - Origin of the Species (1858) a. Structure and Function are intimately linked b. Structure dictates the Function 1. Finch beaks and food on the Galapagos c. Evo luti on "sel ects " mos t favo rabl e Fun ctio ns kidneys/skin of various organisms a. kangaroo rat – desert b. human – land c. sea bass - salty ocean water d. Environment and competition "naturally" select genes that give rise to Structures that have favorable Functions to improve the viability of each species B. Organization of Living Things 1. principles of matter/energy 2. atoms -> molecules 3. complex organic molecules 4. organelles -> cells 5. tissues (Histology) 6. organs 1.

(Physics) (Chemistry) (Biochemistry) (Cellular Biology)

(Physiology/Anatomy) 7. organ/body systems 8. organism (Physiology/Anatomy) *** all fields overlap and contribute to each other See Figure 1 Return II. Basic Functions of Organisms A.

(Physiology/Anatomy)

Maintenance of Boundaries - separation of organism

from outside world a. virus - protein coat around DNA/RNA interior b. cell - cell membrane (semipermeable - selective) c. organism - skin B. Movement - ability to move self and materials a. cells - cilia and flagella (sperm) b. humans - muscle cells (contractility) & bone C. Responsiveness (Irritability) - respond to both Internal and External changes a. nervous system - quick response to change b. endocrine system - medium/longer changes Digestion - breaking down foodstuffs to useable/absorbable form a. digestive system - breakdown/absorb essential materials E. Metabolism - all chemical reactions that occur in cells & body a. anabolism - synthesizing larger molecules b. catabolism - breaking down larger molecules c. regulated primarily by endocrine hormones cellular respiration - breaking bonds of larger molecules for useable energy currency (ATP) a. digestive system - mainly carbohydrate & fats b. respiratory system - oxygen and carbon dioxide c. cardiovascular system - distribution of nutrients and gases

D.

glucose + oxygen -> carbon dioxide + water + ENERGY (stored in ATP) F. Excretion - removing all types of waste from the body a. digestive system - unused foodstuffs b. urinary system - nitrogenous wastes (urea) and electrolyte (salt) balance c. respiratory system - carbon dioxide G. Reproduction - creating more organisms of the same species a. virus - depends on cells for their machinery b. cells - the process of division (mitosis) c. human - sexual (sperm and egg) i. regulated by hormones (especially female) H. Growth - increase in size of cell, organ, or organism a. number of cells can increase (mitosis) b. size of cells can increase (fat cells) III. A. Basic Biological Needs of Humans

Nutrients - molecules for structure and energy 1. 2. carbohydrates - primary energy source & structural a. glycogen, sugars (glucose) proteins - primarily structural & for signaling (hormones and receptors) a. 20 amino acids are basic building blocks b. actin and myosin microfilaments of muscle c. receptors for hormones/neurotransmitters d. neuropeptides (enkephalins of nervous system) 3. fats (lipids) - insulation, energy, structure a. major component of membranes (phospholipids)

b. highest energy content by weight (calories) 4. vitamins - act as cofactors for enzyme functioning 5. minerals - essential for signaling and structure a. nerve signals - Na+, K+, Ca++, Clb. carry oxygen - Fe+ + in hemoglobin c. bone - Ca++, Phosphates B. Oxygen - essential for maximum energy gain from food 1. 2. cellular respiration depends on oxygen nervous system alone uses 25% of all oxygen in humans

C. Water - essential for cellular reactions and transport

D. Body Temperature - essential for cellular reactions ° 1. most human enzymes work best at 37 C (98°F) E. Atmospheric Pressure - for proper absorption of oxygen 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

A. Homeostasis - maintaining relative constancy in response to internal and external changes - dynamic process; changing but relatively constant within limits - concerns all factors relating to well being of organism (see above) - regards maintaining internal environment of body due to internal and external changes 1. Homeostasis refers especially to maintenance of proper conditions for:

a. b. c. d. e. f.

oxygen (02) and carbon dioxide (CO2) levels levels of nutrients in blood (e.g. glucose) electrolyte /salt balance and osmotic pressure (fluid levels) acid-base balance (pH) temperature pressure of body cavities (especially lungs)

Examples of homeostatic mechanisms: 1. proper nutrient levels in the blood a. insulin/glucagon - blood glucose levels 2. proper heart rate and blood pressure a. adrenaline - response to stimuli 3. removing wastes from the blood a. kidneys - nitrogenous wastes (urea) b. respiratory - carbon dioxide 4. maintaining proper oxygen levels in blood a. brain and respiratory - adjust breathing rate 5. body posture and simple muscular reflexes a. nervous system and muscular system

B. General Characteristics of Homeostatic Control Mechanisms

1. Nervous & Endocrine Systems are general controls 2. Basic Organization of Control Mechanisms

a. receptor - monitors internal/external stimuli sends info to control center via afferent path b. control center - analyzes info as it compares to a "set point" for that particular variable 1. variables may include: glucose level, heart rate, blood pressure, urea concentration, oxygen level, tension on a muscle.

c. effector - physiological mechanism acting from the control center via efferent path C. Negative Feedback Mechanisms 1. control mechanism DECREASES intensity of condition to bring back to "set point"

example: regulation of glucose levels in blood a. b. c. d. person eats a candy bar with lots of sugar glucose levels in the blood rise rapidly receptors sense increase in blood sugar control center calls for reduced blood sugar insulin is secreted into the blood stream e. insulin causes effector cells (liver & muscle) to absorb glucose and store it as glycogen g. glucose levels return to normal (0.9 mg/ml blood) See Figure 2 Return D. Positive Feedback Mechanisms (cascade - like a snowball effect) 1. control mechanism INCREASES intensity of condition -

causing a "domino" effect

example: labor contractions during birth a. baby rotates into cervix causing pressure b. receptors sense increased muscle tension c. control center calls for release of oxytocin, causing muscles (effectors) to contract more d. increased muscle tension causes receptors to continue the message to the control center e. more oxytocin is released f. loop continues until baby is delivered and the stimulus is no longer present

See Figure 3 Return 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: I. Matter and Energy

Basic Chemistry

A. Matter - fundamental building blocks of nature 1. elements - basic units of matter B. Energy - capacity to do work (put matter into motion) 1. potential energy - energy stored in a structure a. water stored in a lake uphill b. chemical bonds of glucose molecule 2. kinetic energy - energy in an object in motion a.water in a stream - allows mill to grind corn b. broken glucose bonds -> ATP -> muscles work 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 C. First Law of Thermodynamics 1. “Energy can change from one form to another, but it can never be created or destroyed" (Total Energy In = Total Energy Out) examples: Car Engine vs. Human Body a. Car Engine - gasoline used to run motor to move car Chemical Energy (gas) ---> motion (20%) + heat (79%) + sound (1%)

b. Human Body - food used to move body, digest, think, etc. Chemical Energy (food/glucose) --> physiology (80%) + heat

(20%) II. Organization of Matter (Atoms - Elements) A. Atomic Particles Mass proton neutron electron See Figure 4 Return B. Organization of Periodic Table 1 1 0 Charge +1 neutral -l Characteristics defines element defines isotopes determines element bonding properties

1. 2. 3.

# protons = atomic number (unique for each element)

# protons + # neutrons = atomic mass isotope - same element; different # neutrons # protons + # neutrons = atomic mass 6 7 8 12 13 14

Carbon-12 (99%) Carbon-13 (0.9%) Carbon-14 (0.1%) See Figure 5 Return 4. H H+ H-

6 6 6

# electrons - dictates the NET CHARGE of an atom # electrons 1 0 2 NET CHARGE 0 +1 -1

# protons 1 1 1

ion – any atom with a positive or negative charge anion – an ion with a NEGATIVE charge cation – an ion with a POSITIVE charge III. Electron Shells, the Periodic Table, and Chemical Bonds

A. Electron Shells - electrons occupy "shells" as they orbit around the nucleus (2, 8, 8,..)

B. The Periodic Table of Elements is organized by electron shells H1 2 eLi3 Be4 B5 C6 N7 08 F9 Na11 Mg12 Al13 Si14 P15 8 eSee Figure 6 Return C. He2 Ne10 S16 Cl17 Ar18 SHELL l SHELL28 eSHELL3

Chemical Bonds are formed so that each atom can have the outermost electron shell filled 1. Ionic Bond - one atom donates electron(s) to another a. Example: Sodium Chloride (table salt) Na+Cl2. Covalent Bond - two atoms share one/more electrons a. Example: Methane (CH4), Carbon Dioxide (C02), and Ammonia (NH3) b. Polar Molecule - electron sharing is unequal in the bonds Example: Water (H2O) c. Non-polar Molecule - electron sharing is almost equal Example: Methane (CH4) IV. Elements other than C, H, O, N in Humans

Primary Elements (3% of all body weight) Calcium Ca Bones, teeth, muscle and nerve action, blood clotting Phosphorus P Bones and Teeth, DNA, RNA, ATP. Important in energy transfer Trace Elements (Less than 1 % of body weight altogether) Potassium K Osmotic balance; cell voltage, muscle and nerve

Sulfur Sodium Chlorine Magnesium Iron Copper Zinc Manganese Cobalt Chromium Selenium Molybdenum Flourine Tin Silicon reproduction V. A. 1.

action S Component of proteins (cysteine) and other organic molecules Na Osmotic balance; cell voltage, muscle and nerve action Cl Osmotic balance; cell voltage, muscle and nerve action Mg Co-factor for many enzymes Fe Hemoglobin and many enzymes Cu Co-factor of many enzymes Zn Co-factor of many enzymes Mn Co-factor of many enzymes Co Co-factor of many enzymes and vitamin B12 Cr Co-factor of many enzymes and potentiates Insulin Se Required for normal liver function Mo Co-factor of many enzymes F Teeth and bones Sn Promotes growth (unknown mechanism) Si Growth, bone mineralization, connective tissue synthesis Vanadium V Promotes growth and Chemical Reactions Patterns of Chemical Reactions Chemical Equation - # of atoms of each element same for reactants and products C6H1206 + 602  6H20 + 6C02 2. Synthesis - smaller molecules form larger molecule

A + B  AB (anabolic process) amino acid 1 + amino acid 2 + .......... peptide (protein) sugar 1 + sugar 2 + sugar 3 + ............ polysaccharide (glycogen) 3. Decomposition - larger molecule broken down into smaller molecules

AB  A + B (catabolic process) glycogen ---> glucose + glucose + glucose +...........

4. Displacement - one part is exchanged

AB + C  A + BC glucose + adenosine-P- P-P (ATP)  glucose-P + adenosine-P-P (ADP)

B.

Exergonic vs. Endergonic Reactions 1. Exergonic - energy is released during the reaction

A + B  C + D + ENERGY glucose + oxygen ----> water + carbon dioxide +ENERGY (trapped by ATP) 2. Endergonic - energy required for reaction to proceed A + B + ENERGY  C amino acid 1 + amino acid 2 + ... + ENERGY  peptide (protein) C. Chemical Equilibrium 1. Reversible Reactions A + B  AB and AB  A + B

2. Chemical Equilibrium A + B  AB D. Rates of Chemical Reactions 1. size of reactants species (smaller means faster)

2. temperature (speeds up the particles) 3. concentration (more likely to come together) 4. catalysts (enzymes) - make reacting more convenient VI. Acid- Base Chemistry and the pH Scale A. Water normally exists in an equilibrium reaction with some dissociation H2O  H+ + OHin a beaker of pure water, the ratio of H+ to H20 is about 1/10,000,000

pH = -log10 [H+] = -log10 [10-7] = -(-7) = 7 pH = relative concentration of H+ in a solution of water B. C. D. Acids - compounds which increase the concentration of H+ (pH = 1 to 6) Bases - compounds which decrease the concentration of H+ (pH = 8 to 14) Buffer - compound that prevents large changes in pH of a solution (pH "shock absorber")

Figure 1 Return

Figure 2 Return

Figure 3 Return

Figure 4 Return

Figure 5 Return

Figure 6 Return

Sign up to vote on this title
UsefulNot useful

Master Your Semester with Scribd & The New York Times

Special offer: Get 4 months of Scribd and The New York Times for just $1.87 per week!

Master Your Semester with a Special Offer from Scribd & The New York Times