Chapter 15: The Immune SystemDefense Mechanisms

Against pathogens constitute the immune system Can be grouped into 2 categories:

_____________________ (nonspecific) immunity is inherited as part of structure of each organism

Adaptive (specific) immunity is a function of lymphocytes and changes with exposure

Innate Immunity Distinguishes between “self” and “non-self” Is __________________ of defense against invading pathogens Includes epithelial barriers, high acidity of gastric juice, phagocytosis, and fever

Phagocytosis Is triggered in response to pathogen-associated molecular patterns (PAMPs)

produced only by microorganisms Best known are lipopolysaccharide (LPS) and peptidoglycan from gram

+bacteria Some immune cells have receptors for PAMPs (called _______ receptors)

Is performed by 3 classes of phagocytic cells: Neutrophils - 1st to arrive at infection sites Mononuclear phagocytes - macrophages and __________________ Organ-specific phagocytes in liver, spleen, lymph nodes, lungs, and brain

Fixed phagocytes line sinusoids of liver, spleen, and lymph nodes and remove pathogens

Connective tissue and blood contain mobile leukocytes (WBCs) These are attracted to infection (_________________) by chemokines

WBCs from blood exit capillaries by extravasation (diapedesis) and ingest pathogens

Pseudopods from phagocyte surround pathogen Forming a vacuole that fuses with lysosomes which digest pathogen

Fever Appears to be component of innate immunity __________ are released by WBCs in response to endotoxin from gram– bacteria

Interferons Are polypeptides produced by cells infected with virus that provide short-acting,

non-specific resistance to viral infection in nearby cellsAdaptive Immunity

Is __________________ ability to defend against specific pathogens by prior exposure to those pathogens

Is mediated by production of specific ___________________ by lymphocytes Are molecules that elicit production of antibodies that specifically bind those

antigens Are usually large molecules that are foreign to the body Immune system can distinguish “self” molecules from non-self antigens

Normally makes antibodies only against non-self antigens Large, complex molecules can have a number of ____________ determinant sites

Haptens Are small non-antigenic molecules that become antigens when bound to proteins

Immunoassays Are tests that use specific antibodies to identify a particular antigen The binding of antibody to antigen causes clumping (___________________)

which can be visualizedLymphocytes

Are derived from stem cells in bone marrow Lymphocytes seed thymus, spleen, and lymph nodes with self-replacing

coloniesT lymphocytes (T Cells)

Develop from lymphocytes that seed thymus Do not secrete antibodies Attack infected host cells, cancer cells, and foreign cells

Thus they provide _____________________________ immunity B Lymphocytes (B Cells)

Fight bacterial infections by secreting antibodies into blood and lymph Thus provide humoral immunity

Thymus Is located below the thyroid gland Grows during childhood, gradually regresses after puberty

Then, repopulation is by production in 2o ____________________ organsSecondary Lymphoid Organs

Lymph nodes, spleen, tonsils, and Peyer’s patches In areas where antigens could gain entry to blood or lymph

Lymphocytes migrate constantly through blood and lymph Enhances chance that antibody will encounter its _________________

Local Inflammation Occurs when bacteria enter a break in the skin Inflammatory reaction is initiated by _____________________ mechanisms Complement activation attracts phagocytes to area Attachment of antibodies to antigens amplifies nonspecific responses because of

complement activation And promotes phagocytic activity of neutrophils, macrophages,

and monocytes ( ______________________) Leukocytes move by chemotaxis to inflamed site

Neutrophils arrive 1st, then monocytes, then T cells Mast cells secrete heparin, histamine, prostaglandins

These produce redness, warmth, swelling, pus, and pain Recruit more _____________________ If infection continues, endogenous pyrogens are released

B Lymphocytes (B Cells) Have antibodies on surface that are receptors for antigens

When bound to antigen, are stimulated to divide and secrete antibodies When B cells divide, some progeny become memory cells

Others become ______________________ that produce about 2000 antibodies/sec that are specific for original antigen

This provides active immunity Binding of B cells to antigen also triggers a cascade of reactions that activate

complement proteins which can kill antigen-bearing cells and promote phagocytosis

Antibodies Are proteins called _______________________________ Antibodies have same basic structure but their differences provide for antibody

specificityAntibody Structure

Is in shape of “Y” 2 long heavy (H) chains are joined to 2 shorter light (L) chains Stalk of Y is constant and ___________________________ fragment (Fc) Arms of Y is antigen-binding fragment (Fab) and variable for antibody specifity

Antibody Diversity Each person has about 1020 antibody molecules

With a few million different specificities for any antigen a person might encounter

If a few hundred genes code for Hs and a few hundred for Ls, Recombination of these in developing lymphocytes of marrow

produces antigen-independent diversity Diversity is increased via somatic __________________________

B cells undergo antigen dependent proliferation in 2o lymphoid tissues

The Complement System Is part of nonspecific defense system Activity is triggered by binding of antibodies to antigens (classic pathway) and by

bacterial coat polysaccharides (____________________ pathway) Antibodies label targets for complement system attack and also stimulate

opsonization Is a series of proteins whose activation forms a membrane _______________

complex which perforates a cell causing it to lyse Complement proteins can be subdivided into 3 functional groups:

C1 - recognition C4, C2, C3 - _________________________ C5-C9 - attack (complement fixation)

These form the membrane attack complexMembrane Attack Complex: creates large ____________ in membrane, causing osmotic influx of H2O, lysis, and cell deathComplement Fragments

Attracts phagocytes (chemotaxis) Serve as bridge for phagocytes to victim cell Stimulate __________________ cells to secrete histamine

Which increases blood flow and capillary permeability, bringing in more phagocytes

Killer or Cytotoxic T Cells Carry _______________ cell surface marker Destroy body cells that possess foreign antigens

Usually from a pathogen, malignancy or self cells never seen by immune system

Kill by cell-mediated destruction Secreting perforins which create a pore in victim's membrane and cause

lysis Also secrete ________________ which cause destruction of victim's DNA

Helper and Suppressor T Cells Helper Ts carry CD4 surface marker Indirectly participate by enhancing responses of both killer T cells and B cells ____________________ Ts decrease responses of killer Ts and B cells

Carry CD25 surface marker (and CD4) Help protect against autoimmune responses

Lymphokines Are _____________________ secreted by lymphocytes Usually called interleukin-1, 2, 3 . . . or IL-1, IL-2 . . .

T Cell Receptor Proteins Only protein antigens are recognized by most T cells Foreign antigens are presented on surface of _________________________ cells

Macrophages and dendritic cellsDendritic Cells

Originate in marrow, then migrate to most tissues Prominent where pathogens might enter body

Engulf protein antigens, partially digest them, and display polypeptide fragments on surface for T cells to "see"

Fragments are associated on surface with ________________________antigens to activate Ts

Dendritics migrate to secondary lymphoid organs to attract TsHistocompatibility Antigens

Are on surface of all body's cells except mature RBCs Also called _____________________________ antigens (HLAs)

Are coded for by group of 4 genes on chromosome 6 called the major histocompatibility complex (MHC)

The 4 genes have multiple alleles creating many possible MHC types MHC

MHC genes produce 2 types of cell surface molecules: class-1 and class-2 Class-1s are made by all cells except _______________ Class-2s are made only by antigen-presenting cells and B cells

Antigen is co-presented with a specific MHC marker because Killer T coreceptor CD8 interacts only with class-1s Helper T coreceptor ___________ interacts only with class-2s

Interactions Between Antigen Presenting Cells and LymphocytesT Cell Response to a Virus

When virus infects body, it is phagocytized

Partially-digested pp fragments are displayed Complexed with class-2 MHC molecules, it’s presented to helper T

cellsMacrophage-T cell Interaction

Macrophages then complex with T cells and secrete IL-1 and TNF (tumor necrosis factor)

IL-1 stimulates cell __________________ and proliferation of helper Ts Activated helpers promote macrophage activity and activate B cells

Killer T cell Activity Killer Ts destroy infected cells if class-1 markers are present

Helper T cell-B cell Interactions Activated helper Ts promote _____________________l response of B cells by

binding to their surface antigens and MHC class 2s Causes proliferation of Bs, conversion to plasma cells, and their secretion of

antibodiesDestruction of T cells

Ts have a surface receptor called FAS After infection, Ts begin to produce FAS ligand Binding of FAS to FAS ligand triggers _________________ (cell suicide)

Active ImmunityPrimary and Secondary Responses

1st exposure to pathogen, btw 5-10 days, produce specific antibodies (primary response)

Antibody levels plateau after few days and decline after a few weeks Subsequent exposure to same antigen causes _____________________ response

Antibody production is much more rapid and sustainedClonal Selection Theory

Is mechanism by which secondary immune responses are produced Each B cell produces only 1 kind of antibody and related antigen receptor Exposure to its antigen stimulates a B cell to divide and produce ________ Some become plasma cells to secrete antibodies

Some become memory cells to produce antibodies in the 2o response

Germinal Centers Develop in ___________________ and spleen from a cloned and activated B cell

Which proliferate and undergo hypermutation Generating and secreting diverse antibodies for the 2o immune

response Active Immunity

Development of a 2o response provides active immunity Immunizations induce primary responses by inoculating people with

__________________ or destroyed pathogens (vaccinations) Cause development of B cell clones that can provide 2o response

Immunological Tolerance Tolerance requires continuous exposure to an antigen

Some self-antigens, such as lens protein in eye, are normally hidden from blood

Exposure to such self-antigens results in production of ______________________

Killer T cells that attack self-antigens are called autoreactive T cells 2 possible mechanisms for tolerance:

Clonal deletion theory : tolerance occurs because T cells that recognize self-antigens are destroyed

Clonal ______________ : lymphocytes directed against self-antigens are present throughout life but don't attack self-antigens

Appears to underlie tolerance in B cellsPassive Immunity

Is immune protection by transfer of _____________________ antibodies to a recipient from a donor

Donor was actively immunized Used to treat snakebite, rabies, tetanus, hepatitis

Occurs naturally before and after birth Antibodies from mother pass placenta to fetus in pregnancy and provide

immunity 1st 3 days of nursing, mother makes ___________________, rich in antibodies,

gives immunity Immunological competence (ability to mount a specific immune response) does

not develop until 1 month after birthMonoclonal Antibodies

Prepared for use in research and diagnostic tests Exhibit ______________________ for only 1 antigenic determinant Animal (usually mouse) is injected with antigen, and its B cells harvested from

spleen Bs are hybridized with cancerous myeloma cells to make them immortal Individual Bs are screened and the one with right antibody selected

Allowed to multiply in culture and its clones (________________) are source of large quantity of antibodies

Tumor Immunology Tumor cells arise often but are killed by immune system When cancer shows, the immunological surveillance system of T and natural

killer cells has __________________ Most tumors are clones whose mitosis is uncontrolled by normal inhibitory

mechanisms Tumor cells dedifferentiate Produce surface antigens recognized by immunological _________________ and

destroyed Presence of such antigens provides basis of laboratory diagnosis for some

cancers Natural Killer (NK) Cells

Are lymphocytes related to T cells Provide first line of cell-mediated defense (innate) Have surface ____________________ that help fight viruses, bacteria, parasites

and malignant cells

NK cells destroy tumors in a non-specific fashion; backed up by specific response of killer Ts

Kill with perforins and granzymesImmunotherapy for Cancer

Most strategies involve boosting, or directing, patients own immune responses _______________________ and interleukins have been useful in treatment of

some forms of cancerEffects of Aging and Stress

Little is known about why susceptibility to cancer is so variable Cancer risk increases with age

Thymus function declines with age Tumors grow faster in ________________ animals

Autoimmune Diseases Are produced by failure of immune system to recognize and tolerate self-antigens

Autoreactive T cells are formed and B cells produce _________________ Afflicts women twice as often as men Failure of self-tolerance may be due to:

An antigen that does not normally circulate in blood being presented to immune system

E.g. in Hashimoto's thyroiditis, antibodies are stimulated to attack _________________ (normally hidden from immune surveillance)

Combination of a self-antigen, that is otherwise tolerated, with a foreign hapten

E.g. in thrombocytopenia (low platelet count), platelets are destroyed because they combine with victim's medications

Antibodies being produced that are directed against other antibodies Happens with _____________________ arthritis

Antibodies against foreign antigens cross-reacting with self-antigens This can happen with rheumatic fever

Self-antigens being presented to helper T cells together with class-2 MHC molecules

This happens in Type I diabetesImmune Complex Diseases

Involve formation of immune complexes that are free and not attached to a cell These activate complement proteins and promote ____________________ Can result from infections by bacteria, parasites, viruses

Can result from formation of complexes between self-antigens and autoantibodies This occurs in rheumatoid arthritis and lupus

Allergy (Hypersensitivity) Is an abnormal immune response to allergens Comes in 2 forms: immediate and ______________________ hypersensitivity

Immediate is due to abnormal B cell response to allergen; causes effects in secs to mins

Caused by foods, bee stings, pollen Delayed is abnormal T cell response that causes symptoms 24-72 hrs after

exposure

Immediate Hypersensitivity Dendritic cells stimulate helper Ts; B and plasma cells secrete IgE antibodies

IgEs do not circulate in blood; are attached to mast cells and ______________________

When re-exposed to same allegen, IgE bind it and stimulate secretion of histamine

Producing allergy symptoms Histamine increases capillary permeability and enhances immune

responseDelayed Hypersensitivity

Symptoms take longer to develop (hrs to days) Is a cell-mediated T cell response

Symptoms caused by secretion of _______________________, not histamine Antihistamines provide little benefit

Examples include contact dermatitis caused by poison ivy, oak, or sumac

Chapter 16: Respiratory PhysiologyRespiration

Includes: ventilation, gas exchange, and O2 utilization (___________ respiration) Ventilation moves air in and out of lungs for gas exchange with blood

(external respiration) Gas exchange between blood and tissues, and O2 use by tissues is

_______________________ respiration Gas exchange is passive via diffusion

Structure of Respiratory System Air passes from mouth to trachea to right and left bronchi to bronchioles to

terminal bronchioles to respiratory bronchioles to alveoli Gas exchange occurs in respiratory bronchioles and alveoli ( ___________ zone) All other structures constitute the conducting zone Gas exchange occurs across the 300 million alveoli (60-80 m2 total surface area)

Only 2 thin cells are between lung air and blood: 1 alveolar and 1 endothelial cell

Alveoli Are polyhedral in shape and clustered at ends of ________________ bronchioles,

Air in 1 cluster can pass to others through poresConducting Zone

Warms and humidifies inspired air Mucus lining filters and cleans inspired air

Mucus moved by cilia to be expectorated Thoracic Cavity

Is created by the ___________________, a dome-shaped sheet of skeletal muscle Contains heart, large blood vessels, trachea, esophagus, thymus, and lungs Intrapleural space is thin fluid layer between visceral pleura covering lungs and

____________________ pleura lining thoracic cavity wallsPhysical Aspects of Ventilation

Ventilation results from pressure differences induced by changes in lung volumes Air moves from higher to lower pressure Compliance, elasticity, and ________________ _______________ of

lungs influence ease of ventilation Intrapulmonary and Intrapleural Pressures

Visceral and parietal pleurae normally adhere to each other so that lungs remain in contact with chest walls

And expand and contract with thoracic cavity Intrapleural space contains a thin layer of lubricating fluid During inspiration, ________________ _________________is about -3 mm Hg

pressure; during expiration is about +3 mm Hg Positive transmural pressure (intrapulmonary - intrapleural ) keeps lungs inflated

Boyle’s Law (P=1/V) Implies that changes in intrapulmonary pressure occur as a result of changes in

lung volume Pressure of gas is _____________________ proportional to volume

Increase in lung volume decreases intrapulmonary pressure causing inspiration

Decrease in lung volume raises intrapulmonary pressure causing expirationCompliance

Is how easily lung expands with pressure Or _______________in lung volume per change in transmural pressure (DV/DP) Is reduced by factors that cause resistance to distension

Elasticity Is tendency to return to initial size after distension Due to high content of elastin proteins Elastic tension __________ during inspiration and reduced by recoil in expiration

Surface Tension (ST) And elasticity are forces that promote alveolar collapse and resist distension Lungs secrete and absorb fluid, leaving a thin film of fluid on alveolar surface

This film causes ST because H20 molecules are attracted to other H2O molecules

_________________________________ states that pressure in alveolus is directly proportional to ST; and inversely to radius of alveoli

Thus, pressure in smaller alveoli would be greater than in larger alveoli, if ST were same in both

Surfactants Consists of phospholipids secreted by ___________________ alveolar cells Lowers ST by getting between H2O molecules, reducing their ability to attract

each other via hydrogen bonding Prevents ST from collapsing alveoli Surfactant secretion begins in late fetal life __________________ are often born with immature surfactant system (=

Respiratory Distress Syndrome or RDS) Have trouble inflating lungs

Mechanics of Breathing Pulmonary ventilation consists of inspiration (= __________________) and

____________________ (= exhalation) By alternately increasing and decreasing volumes of thorax and lungs

Quiet Breathing Inspiration occurs mainly because diaphragm contracts, increasing thoracic

volume vertically Parasternal and external intercostal contraction contributes a little by raising ribs,

increasing thoracic volume laterally Expiration is due to ____________________ recoil

Deep Breathing Inspiration involves contraction of extra muscles to elevate ribs: scalenes,

pectoralis minor, and __________________________________ muscles Expiration involves contraction of internal intercostals and abdominal muscles

Pulmonary Function Test Assessed clinically by spirometry, a method that measures volumes of air moved

during inspiration and expiration Anatomical dead space is air in conducting zone where no gas exchange occurs ____________ _____________ is amount of air expired/breath in quiet breathing

Vital capacity is amount of air that can be forcefully exhaled after a maximum inhalation

= sum of inspiratory reserve, tidal volume, and __________ ___________Pulmonary Disorders

Are frequently accompanied by dyspnea, a feeling of shortness of breath Asthma results from episodes of obstruction of air flow thru bronchioles

Caused by inflammation, mucus secretion, and ______________________ Provoked by allergic reactions that release IgE, by exercise, by breathing

cold, dry air, or by aspirin _____________________ is a chronic, progressive condition that destroys

alveolar tissue, resulting in fewer, larger alveoli Reduces surface area for gas exchange and ability of bronchioles to

remain open during expiration Collapse of bronchiole during expiration causes ____________________,

decreasing gas exchange Commonly occurs in long-term smokers

Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease (COPD) involves chronic inflammation

accompanied by narrowing of airways and destruction of alveolar walls Most people with COPD are ___________________

Factors Affecting Gas Exchange Partial pressure is pressure that a particular gas in a mixture exerts independently Dalton’s Law states that total pressure of a gas mixture is the __________ of

partial pressures of each gas in mixture Atmospheric pressure at sea level is 760 mm Hg

PATM = PN2 + PO2 + PCO2 + PH2O = 760 mm HgGas Exchange in Lungs

Is driven by differences in partial pressures of gases between alveoli and _______ Is facilitated by enormous surface area of alveoli, short diffusion distance between

alveolar air and capillaries, and tremendous density of capillaries Partial Pressure of Gases in Blood

Henry’s Law says blood O2 depends on _____________ of O2, blood temperature (constants), and partial pressure of O2 (PO2), which varies with _____________

Blood PO2 and PCO2 Measurements At normal PO2 arterial blood has about 100 mmHg PO2

PO2 is about 40 mmHg in systemic veins PCO2 is 46 mmHg in systemic veins

Pulmonary Circulation _______________ of blood flow through pulmonary circuit equals flow through

systemic circulation Pulmonary arterioles constrict where alveolar PO2 is low and dilate where high

This matches ____________________ to perfusionLung Ventilation/Perfusion ratios

Normally, alveoli at apex of lungs are underperfused and overventilated Alveoli at base are overperfused and underventilated

Control of Ventilation

Brain Stem Respiratory Centers Automatic breathing is generated by a _________________ _________________

in medulla oblongata Consists of inspiratory neurons that drive inspiration and expiratory

neurons that inhibit inspiratory neuronsPons Respiratory Centers

Inspiratory neurons stimulate spinal motor neurons that innervate respiratory muscles

Expiration is passive and occurs when _______________________ are inhibitedChemoreceptors

Automatic breathing is influenced by activity of chemoreceptors that monitor blood PCO2, PO2, and pH

Central chemoreceptors are in medulla Peripheral chemoreceptors are in large arteries near heart (____________ bodies)

and in carotids (carotid bodies)Effects of Blood PCO2 and pH on Ventilation

Chemoreceptors modify ventilation to maintain normal CO2, O2, and pH levels PCO2 is most _________________ because of its effects on blood pH

H2O + CO2 « H2CO3 « H+ + HCO3-

Hyperventilation causes low CO2 (hypocapnia) Hypoventilation causes high CO2 (hypercapnia) Brain chemoreceptors are responsible for greatest effects on ventilation

H+ can't cross BBB but ______________ can, which is why it is monitored and has greatest effects

Peripheral chemoreceptors do not respond to PCO2, only to H+ levelsEffects of Blood PO2 on Ventilation

Low blood PO2 (_________________) has little effect on ventilation Influences chemoreceptor sensitivity to PCO2 PO2 has to fall to about half normal b4 ventilation is significantly affected Emphysema blunts chemoreceptor response to PCO2

Often ventilation is stimulated by _______ drive rather than PCO2

Hemoglobin (Hb) and O2 Transport Loading of Hb with O2 occurs in lungs; unloading in tissues Each Hb has 4 ____________ polypeptide chains and 4 heme groups that bind O2

Each heme has a ferrous ion that can bind 1 O2

So each Hb can carry 4 O2s Most O2 in blood is bound to Hb inside RBCs as ______________________ Each RBC has about 280 million molecules of Hb Hb greatly increases O2 carrying capacity of blood Methemoglobin contains ferric iron (Fe3

+) -- the oxidized form Lacks electron to bind with O2 Blood normally contains a small amount

Carboxyhemoglobin is heme combined with _____________________________ Bond with carbon monoxide is 210 times stronger than bond with oxygen

So heme can't bind O2

O2-carrying capacity of blood depends on its Hb levels

In __________________, Hb levels are below normal In polycythemia, Hb levels are above normal

Hb production controlled by erythropoietin (EPO) Production stimulated by low PO2 in kidneys

Hb levels in men are ____________ because androgens promote RBC production High PO2 of lungs favors loading; low PO2 in tissues favors unloading

Oxyhemoglobin Dissociation Curve Reflects loading and unloading of O2

Affinity decreases when pH decreases (_________ _________)or temp increases Occurs in tissues where temp, CO2 and acidity are high

Effects of 2,3 DPG on O2 Transport RBCs have no mitochondria; can’t perform aerobic respiration

__________________ is a byproduct of glycolysis in RBCs Its production is increased by low O2 levels

Fetal hemoglobin (HbF) has 2 g-chains in place of b-chains of HbA HbF can’t bind DPG, causing it to have higher O2 affinity

Facilitates O2 transfer from mom to babySickle-cell Anemia

Sickle-cell anemia affects 8-11% of __________________ Americans HbS has valine substituted for glutamic acid at 1 site on b chains At low PO2, HbS crosslinks to form a “gel” inside RBCs

Makes RBCs less flexible and more _____________Thalassemia

Thalassemia affects primarily people of Mediterranean descent Has decreased synthesis of a or b chains; increased synthesis of g chains

Myoglobin Is a red pigment found exclusively in ___________________ muscle

Slow-twitch skeletal and cardiac muscle fibers are rich in myoglobin Has only 1 globin; binds only 1 O2

Has higher ______________ for O2 than Hb; is shifted to extreme left Releases O2 only at low PO2

Serves in O2 storage, particularly in heart during systoleCO2 Transport and Acid-Base Balance

CO2 transported in blood as dissolved CO2 (10%), carbaminohemoglobin (20%), and bicarbonate ion, HCO3

-, (________) In RBCs carbonic anhydrase catalyzes formation of H2CO3 from CO2 + H2O

Chloride Shift High CO2 levels in tissues

Results in high H+ and HCO3- levels in RBCs

HCO3- diffuses down conc and charge gradient into blood causing

RBC to become more _____________________ So Cl- moves into RBC (chloride shift)

Reverse Chloride Shift In lungs, CO2 is breathed out Binding of O2 to Hb decreases its affinity for H+

H+ combines with HCO3- and more CO2 is formed

Cl- diffuses down conc and charge gradient out of RBC (___________________)Acid-Base Balance in Blood

Blood pH is maintained within narrow pH range by lungs and kidneys (normal = 7.4 )

Most important _________________ in blood is bicarbonate H2O + CO2 « H2CO3 « H+ + HCO3

-

Excess H+ is buffered by HCO3- Kidney's role is to excrete H+ into urine 2 major classes of acids in body:

A ________________________ can be converted to a gas E.g. CO2 in bicarbonate buffer system can be breathed out

H2O + CO2 « H2CO3 « H+ + HCO3-

All other acids are nonvolatile and cannot leave blood E.g. lactic acid, fatty acids, ketone bodies

______________________ is when pH < 7.35; alkalosis is pH > 7.45 Respiratory acidosis caused by hypoventilation

Causes rise in blood CO2 and thus carbonic acid Respiratory alkalosis caused by _____________________________

Results in too little CO2 Metabolic acidosis results from _________________ of nonvolatile acids

E.g. excess ketone bodies in diabetes or loss of HCO3- in diarrhea Metabolic alkalosis caused by too much HCO3- or too little nonvolatile acids (e.g.

from vomiting out stomach acid) Normal pH is obtained when ratio of HCO3- to CO2 is _____________ Henderson-Hasselbalch equation uses CO2 and HCO3- levels to calculate pH:

pH = 6.1 + log [HCO3-] [0.03PCO2]

Respiratory Acid-Base Balance Ventilation usually adjusted to ____________ rate to maintain normal CO2 levels With hypoventilation not enough CO2 is breathed out in lungs

Acidity builds, causing respiratory acidosis With hyperventilation too much CO2 is breathed out in lungs

_________________ drops, causing respiratory alkalosisExercise and Altitude EffectsVentilation During ExerciseDuring exercise, arterial PO2, PCO2, and pH remain fairly constant

During exercise, breathing is deeper and faster, more air going to lungs (________________________)

With neurogenic mechanism, sensory activity from exercising muscles stimulates ventilation;

With ______________ mechanism, either PCO2 and pH may be different at chemoreceptors than in arteries

Chapter 17: Physiology of the KidneysKidney Functions

Regulate plasma and __________________________fluid Thru urine formation, kidneys regulate:

Volume of blood plasma, Waste products in blood Concentration of electrolytes, Plasma pH

Structure of Kidneys Paired kidneys are on either side of the vertebral column and below the

diaphragm. About the size of fist ________________ contains many capillaries and outer parts of nephrons Medulla consists of renal pyramids separated by renal columns

Pyramid contains minor calyces which unite to form a major calyx Major calyces form renal pelvis which conducts urine to ureters and into bladder

Bladder has a smooth muscle wall, ______________________ muscle Stretch can cause spontaneous APs and contraction Also innervated and controlled by parasympathetic

Nephron Is __________________ unit of kidney; forms urine. >1 million nephrons/kidney Is a long tube and has associated blood vessels Blood enters kidney through renal artery, interlobar arteries, arcuate arteries and

then interlobular arteries give rise to afferent arterioles which supply glomeruli A mass of capillaries in ___________________________ capsule producing

filtrate into nephron tubule Efferent arteriole drains glomerulus into peritubular capillaries (vasa recta) Blood from peritubular capillaries enters veins

Nephron Tubules Glomerular capsule leads into _______________________ convoluted tubule

(PCT), to descending and ascending limbs of Loop of Henle (LH), and ___________________ convoluted tubule (DCT)

Tubule ends where it empties into collecting duct (CD)Glomerular (Bowman’s) Capsule

Surrounds glomerulus. Together they form renal _______________________ Is where glomerular filtration occurs. Filtrate passes into PCT

Proximal Convoluted Tubule Walls consist of single layer of cuboidal cells with millions of microvilli

Which increase surface area for ______________________________ Type of Nephrons

Cortical nephrons originate in outer 2/3 of cortex Juxtamedullary nephrons originate in inner 1/3 cortex. Have long LHs

Glomerular Filtration Glomerular capillaries and Bowman's capsule form a filter for blood

Glomerular Caps are fenestrated—allows any plasma molecule to pass Filtrates pass through narrow _________________________________ between

pedicels (foot processes) of podocytes of glomerular capsule Plasma proteins are mostly excluded from the filtrate because of large size and

negative charge

Some protein (albumin) normally enters the filtrate but most is reabsorbed Defects in slit diaphragm allows protein in the urine (__________)

Glomerular Ultrafiltrate Is fluid that enters glomerular capsule, whose filtration was driven by bld pressure

Glomerular Filtration Rate Is _________________________ of filtrate produced by both kidneys/min

Averages 115 ml/min in women; 125 ml/min in men Totals about 180L/day (45 gallons. Most filtered water must be reabsorbed

Regulation of GFR Is controlled by extrinsic and intrinsic (autoregulation) mechanisms Constriction/dilation of _____________________ arterioles affects rate of blood

flow to glomeruli & GFRSympathetic Effects: Sympathetic activity ______________________ afferent arteriole

Helps maintain BP and shunts blood to heart and musclesRenal Autoregulation

Allows kidney to maintain a _________________ GFR over wide range of BPs When average BP drops to 70 mm Hg afferent arteriole dilates When average BP increases, afferent arterioles constrict Is also maintained by negative feedback between afferent arteriole and volume of

filtrate _________________________________ feedback) Increased flow of filtrate sensed by macula densa in thick ascending LH

Signals afferent arterioles to constrict Functions of Nephron SegmentsReabsorption of Salt and H2O

PCT returns most molecules and H2O in filtrate back to _____________________ capillaries

About 180L/d of ultrafiltrate produced; only 1–2L of urine excreted/24h Urine volume varies according to needs of body Minimum of 400 ml/day urine necessary to excrete metabolic

wastes (______________________________________) Return of filtered molecules is called reabsorption Water is never transported

Other molecules are transported and water follows by ________________Significance of PCT Reabsorption

~65% Na+, Cl-, and H2O is reabsorbed in PCT and returned to bloodstream An additional 20% is reabsorbed in descending loop of Henle

The other 15% is reabsorbed variably, depending on level of ___________Descending Limb LH

Is permeable to H2O. Is impermeable to, and does not ___________________ salt H2O diffuses out of filtrate and is reabsorbed by capillaries

Ascending Limb LH Impermeable to H2O; permeable to salt; thick part ATs salt out of filtrate

AT of salt causes filtrate to become ___________________ by end of LHCountercurrent Multiplier System

Countercurrent flow and proximity allow descending and ascending limbs of LH to interact and build ____________________________ in medulla

Salt pumping in thick ascending part raises osmolality around descending limb, causing more H2O to diffuse out of filtrate

Vasa Recta: Is important component of countercurrent multiplier Permeable to salt, H2O (via aquaporins), and ___________________ Reabsorbs H2O coming out of descending limb Descending area has urea _______________________. Ascending area has

fenestrated capillariesEffects of Urea

Urea contributes to high osmolality in medulla Deep region of collecting duct is _____________ to urea and transports it

Collecting Duct (CD): Plays important role in water conservation Is impermeable to salt in medulla. Permeability to H2O depends on levels of ADH

ADH Is secreted by post pituitary in response to dehydration Stimulates insertion of ___________________________ (water channels) into

plasma membrane of CD When ADH is high, H2O is drawn out of CD by hi osmolality of interstitial fluid

Renal Clearance Ability of kidney to remove substances from blood and excrete them in urine Occurs by filtration and by _________________________ Reabsorption decreases renal clearance; secretion increases clearance ____________________ rate = (filtration rate + secretion rate) - reabsorption rate

Secretion of Drugs Many drugs, toxins, metabolites are secreted by membrane transporters in PCT Many ______________________ molecules (xenobiotics) are eliminated by this

system at a more rapid rate than by glomerular filtrationInulin Measurement of GFR

Inulin , a fructose polymer, is useful for measuring GFR because is neither reabsorbed nor secreted. Amount filtered ___________ amount excreted

Renal Plasma Clearance (RPC) Vol. of plasma from which a subst is _______________________ removed/min

by urine excretion If subst is filtered but not reabsorbed then all filtered will be excreted RPC = GFR If substance is filtered and reabsorbed then RPC ___________ GFR If substance is filtered but also secreted and excreted then RPC will be > GFR

(=120 ml/ min) RPC = V x U/PClearance of Urea

Urea is __________________ filtered into glomerular capsule Urea clearance is 75 ml/min, compared to clearance of inulin (120 ml/min)

Thus 40-60% of filtered urea is always reabsorbedMeasurement of Renal Blood Flow

___________________ of blood in glomerulus is filtered Rest passes into efferent arteriole and back into circulation Substances not filtered can still be cleared by AT (secretion) into tubules

Total Renal Blood Flow Using PAH PAH clearance is used to measure ________________ renal blood flow

Normally averages 625 ml/min It is totally cleared by ______________________ pass through a nephron So it must be both filtered and secreted

\ Total renal blood flow = PAH clearance/0.55

Glucose and Amino Acid Reabsorption Filtered glucose and amino acids are normally _________ reabsorbed from filtrate

Occurs in PCT by carrier-mediated cotransport with Na+Glycosuria

Is presence of glucose in urine Occurs when glucose > 180-200mg/100ml plasma ( renal ___________________

Glucose is normally absent because plasma levels stay below this value Hyperglycemia has to exceed renal plasma threshold Diabetes mellitus occurs when hyperglycemia results in ______________

Electrolyte Balance Kidneys regulate Na+, K+, H+, HCO3

-, Cl-, & PO4-3, match excretion to ingestion

Role of Aldosterone in Na+/K+ Balance 90% filtered Na+ and K+ reabsorbed before DCT Regulated by _________________ (controls K+ secretion and Na+ reabsorption)

K+ Secretion Is only way K+ ends up in urine Is directed by aldosterone and occurs in DCT and cortical CD

High K+ or low Na+ will increase aldosterone and K+ secretionJuxtaglomerular Apparatus

Specialized region in nephron where afferent arteriole & ________________ ascending limb meet

Renin-Angiotensin-Aldosterone Stsyem Is activated by release of renin from __________________ cells within afferent

arteriole Renin converts angiotensinogen to angiotensin I which is converted to

Angio II by angiotensin-converting enzyme (ACE) in lungs Angio II stimulates release of aldosterone

Regulation of Renin Secretion Inadequate intake of NaCl always causes _____________________blood volume

Because lower osmolality inhibits ADH, causing less H2O reabsorption Low blood volume and renal blood flow stimulate renin release

Macula Densa Cells respond to levels of Na+ in filtrate

Inhibit ________________ secretion when Na+ levels are high Causing less aldosterone secretion, more Na+ excretion

Atrial Natriuretic Peptide (ANP) Is produced by atria due to stretching of walls. Acts opposite to aldosterone Stimulates salt and H2O ____________________. Acts as an endogenous diuretic

Renal Acid-Base Regulation Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3- Most H+ secretion occurs across PCT wall in exchange for Na+, Na+/H+ antiporter

Normal urine is acidic (____________), kidneys reabsorb almost all HCO3- &

excrete H+Reabsorption of HCO3

- in PCT When urine is _________________, HCO3

- combines with H+ to form H2CO3, catalyzed by CA

H2CO3 splits into HCO3- and H+ ; HCO3- diffuses into bloodUrinary Buffers

Nephron _______________ produce urine with pH < 4.5 Excretes more H+ by buffering H+s with HPO4

-2 or NH3 before excretion Diuretics: Used to ______________ blood volume in hypertension, congestive heart failure, or edema

Increase volume of urine by increasing proportion of glomerular filtrate that is excreted

______________ diuretics are most powerful; inhibit AT salt in thick ascending limb of LH

Kidney Diseases In acute renal failure, kidney function is impaired

Rise in blood creatinine and ____________________ in RPC of creatinine In renal insufficiency, nephrons have been destroyed as a result of a disease

Clinical manifestations include salt and H2O retention and uremia (high plasma urea levels)

Treatment includes _________________________ Urea and other wastes are removed

Chapter 18: The Digestive SystemFunctions of GI TractMotility: Is movement of food through GI tract by means of:

Ingestion --taking food into mouth Mastication --chewing food and mixing it with saliva ___________________ --swallowing food Peristalsis --rhythmic wave-like contractions move food through GI tract

Secretions: Includes release of exocrine and endocrine products into GI tract Exocrine secretions include: HCl, H2O, HCO3-, _____________, lipase, pepsin,

amylase, Endocrine includes hormones secreted into stomach and small intestine to help

regulate GI system. E.g. gastrin, secretin, CCK, GIP, GLP-1, guanylin, ______.Absorption: Is passage of digested end products into blood or lymphStorage & Elimination: Temp storage and elimination of indigestible components of foodDigestive System

Is composed of GI tract (alimentary canal) and accessory digestive organs GI tract is 30 ft long; extends from mouth to anus Organs include oral cavity, pharynx, esophagus, ________________, small &

large intestine Accessory organs are teeth, tongue, salivary glands, liver, gallbladder, & pancreas Layers of GI Tract are called tunics: mucosa, submucosa, muscularis, and serosa Mucosa: Is the absorptive and secretory layer lining lumen of GI tract Highly folded with villi to increase _____________________ area Contains lymph nodules, mucus-secreting goblet cells, and thin layer of muscle Submucosa: Is a thick, highly vascular layer of connective tissue where absorbed

molecules enter blood and lymphatic vessels Contains _________________ & nerve plexuses that carry ANS activity to

muscularis mucosae Muscularis: Is for segmental contractions and peristaltic movement through GI Has an inner circular and outer longitudinal layer of smooth muscle

These layers move food through tract while pulverizing and mixing it _______________________ plexus between these layers is major nerve

supply to GI tract Serosa: Is outermost layer; serves to bind and protect Consists of areolar connective tissue with layer of simple squamous epithelium

From Mouth to Stomach Mastication (chewing) mixes food with saliva which contains salivary _________

An enzyme that catalyzes partial digestion of starch Deglutition (swallowing) begins as voluntary activity

Oral phase is voluntary and forms a food ___________ Pharyngeal and esophageal phases are involuntary and cannot be stopped Larynx is raised so that epiglottis covers entrance to respiratory tract

Esophagus connects pharynx to stomach Upper third is skeletal muscle, then mixture of skeletal and smooth Last portion has only smooth, passes thru diaphragm via esophageal hiatus

_________________ propels food thru GI tract (wave-like muscular contractions)

Food in stomach, the gastroesophageal sphincter constricts, stops refluxStomach: Is most distensible part of GI tract; Empties into the duodenum

For food storage, initial digestion of proteins; killing bacteria with high acidity; moving soupy food mixture (_____________) into intestine

Is enclosed by gastroesophageal sphincter on top and pyloric sphincter on bottom Is divided into 3 regions: Fundus, Body, Antrum Inner surface of stomach is highly folded into _____________________ Contractions of stomach churn chyme, mixing it with gastric secretions Gastric mucosa has gastric pits in its folds Cells that line folds deeper in the mucosa, are exocrine _____________________ Gastric glands contain cells that secrete different products that form gastric juice

Goblet cells secrete mucus Parietal cells secrete HCl &intrinsic factor (for B12 absorption in intestine __________________________ secrete pepsinogen (precursor for pepsin)

Enterochromaffin-like cells secrete histamine and serotonin G cells secrete gastrin; D cells secrete somatostatin

HCl in Stomach Is secreted in response to the hormone gastrin; and ACh from vagus

Both stimulate release of histamine causing parietal cells to secrete HCl Makes gastric juice very acidic; ___________________________ proteins to

make them more digestible Converts pepsinogen into pepsin; Pepsin is more active at low pHs

Digestion and Absorption in Stomach Proteins are partially digested by pepsin _________________ digestion by salivary amylase is soon inactivated by acidity Alcohol and aspirin are the only commonly ingested substances that are absorbed

Gastric and Peptic Ulcers Peptic ulcers : erosions of mucous membranes of stomach or duodenum by _____ Helicobacter pylori infection is associated with ulcers; Antibiotics are useful

Small Intestine Longest part of GI ; appr.3m long; Duodenum: 1st 25cm after pyloric sphincter _________________ is next 2/5s; Ileum is last 3/5s; empties into large intestine Absorption of digested food occurs in SI; Helped by long length and surface area Surface area increased by foldings and projections; Large folds: plicae circulares Micr. finger-like projections are villi; Apical hair-like projections are __________ Each villus is covered with columnar epithelial cells interspersed with goblet cells Epithelial cells of villi exfoliate and replaced by mitosis in crypts of Lieberkuhn Inside each villus are lymphocytes, capillaries, and _______________________ Hair-like microvilli projecting from surface of epithelial cell create a brush border

Intestinal Enzymes attached to microvilli are brush border enzymes not secreted in lumen Enzyme active sites are exposed to chyme

Intestinal Contraction and Motility Peristalsis is weak and slow; pyloric end pressure greater than distal end _____________________________ is major contractile activity of SI

Is contraction of circular smooth muscle to mix chymeLarge Intesine (LI) or Colon

Has no digestive function; absorbs H2O, electrolytes, folic acid, B and K vitamins, Has no ______________or________________; has microflora of about 400 sps

of commensal bacteria which produce folic acid and vitamin K and ferment indigestible food fatty acids Extends from ileocecal valve at end of SI to anus; bulges to form pouches (haustra Chyme enters cecum, ascending, transverse, descending, sigmoid colon, rectum,

Fluid and Electrolyte Absorption in LI SI absorbs most water but LI absorbs __________ of water it receives, by osmosis Salt and water reabsorption stimulated by aldosterone LI can also secrete H2O via AT of NaCl into intestinal lumen

Defeacation After electrolytes and water have been absorbed, waste material passes to rectum,

creating urge to defecateLiver

Liver is the largest internal organ __________________________ form hepatic plates that are 1–2 cells thick

Plates are separated by sinusoids which are fenestrated and permeable even to proteins. Contain phagocytic ______________________ cells

A damaged liver can regenerate itself from mitosis of surviving hepatocytes In some cases, such as alcohol abuse or viral hepatitis, regeneration does

not occur. Can lead to liver fibrosis and ultimately _________________Hepatic Portal System

Food absorbed in SI is delivered 1st to liver Capillaries in digestive tract drain into the _________________ ______ vein

which carries blood to liver. Hepatic vein drains liver. Liver also receives blood from hepatic artery

Liver __________________ are functional units formed by hepatic plates In middle of each is central vein. At edge of each lobule are branches of hepatic

portal vein and artery which open into sinusoids Bile is secreted by hepatocytes into bile canaliculi which empty into ________

________________ which flow into hepatic ducts that carry bile away from liverFunctions of the Liver

Bile production and secretion amounts to 250–1500 ml/day ____________________ (bilirubin) is produced in spleen, bone marrow, and liver

Is a derivative of heme groups (minus iron) from HbDetoxification of Blood

Liver can remove hormones, drugs, and other biologically active molecules from blood by:

Excretion into bile. _______________________ by Kupffer cells Chemical alteration of molecules: Liver converts ammonia to urea

Secretion of Glucose, Triglycerides, and Ketones Liver helps regulate blood glucose by removing it from or releasing it to blood

Removes it via glycogenesis and lipogenesis Or produces it via __________________________ and gluconeogenesis

Can convert free fatty acids into ketone bodies (ketogenesis) Production of Plasma Proteins

___________________ makes up 70% of total plasma protein and contributes most of the colloid osmotic pressure of blood

Globulins transport cholesterol and hormones, and are involved in blood clottingGallbladder and Pancreas

Is a sac-like organ on inferior surface of liver, stores and conc bile from liver When SI is empty, sphincter of Oddi in common bile duct closes and bile

is forced into ___________________. Expands as it fills with bile When food is in SI, sphincter of Oddi opens, gall bladder contracts, and

bile is ejected thru cystic duct into common bile duct then to duodenumPancreas

Is located behind stomach. Has both endocrine and exocrine functions Endocrine function performed by ________________________________

Secretes insulin and glucagon Exocrine secretions include bicarbonate solution and digestive enzymes

Pass in pancreatic duct to SI. Exocrine secretory units are _______Pancreatic Juice

Contains water, bicarbonate, and digestive enzymes Digestive enzymes include amylase for starch, _____________ for proteins and

lipase for fats Most pancreatic enzymes are produced in inactive form (zymogens)Trypsin is activated by brush border enzyme, enterokinase, Trypsin activates others

Neural and Endocrine Regulation___________nerve is heavily involved in regulating and coordinating digestive

activities Endocrine hormones include secretin, gastrin, CCK, and GIP

Regulation of Gastric Function Gastric motility and secretion occur automatically Extrinsic control of gastric fxn includes cephalic, gastric, and intestinal phases Cephalic Phase: Refers to control by brain of vagus activity Stimulated by sight, smell, and taste of food Activation of vagus causes:

Chief cells to secrete pepsinogen; G cells to secrete gastrin Indirectly stimulates parietal cells to secrete HCl

Gastric Phase: Arrival of food in stomach stimulates gastric phase Gastric secretion caused by distension of stomach and chemical nature of chyme Short pp and aa stimulate G cells to secrete gastrin and chief cells -___________; Secretion of HCl is also regulated by a negative feedback mechanism:

HCl secretion decreases if pH < 2.5; at pH 1 gastrin secretion stopsIntestinal Phase

Begins when chyme enters the SI This causes a neural reflex that inhibits gastric __________________ and

secretionEnteric Nervous System

Peristalsis is controlled by enteric NS ACh and substance P stimulate smooth muscle contraction above bolus NO, VIP, and ATP stimulate smooth muscle relaxation below bolus

Secretion of Pancreatic Juice Secretion of pancreatic juice and bile is stimulated by ______________ and ____ Secretin is secreted in response to duodenal pH < 4.5 CCK is secreted in response to fat and protein content of chyme in duodenum

Stimulates production of __________________ enzymesDigestion and Absorption of Carbohydrates

Most CH2O are ingested as starch Salivary amylase begins starch digestion Pancreatic amylase converts starch to _________________________

Oligosaccharides hydrolyzed by SI brush border enzymesDigestion and Absorption of Protein

Begins in stomach when pepsin digests proteins to form polypeptides __________________ (trypsin, chymotrypsin,) cleave peptide bonds inside of pp Exopeptidases (carboxypeptidase, aminopeptidase) cleave ends of polypeptides Protein digestion in SI results in free amino acids, dipeptides, and tripeptides

Which are transported into SI cells where di- and tripeptides are broken down to amino acids and are secreted into blood

Digestion and Absorption of Lipids Occurs in SI. Arrival of lipids in duodenum causes secretion of bile Fat is __________________ by bile salt micelles

Forms tiny droplets of fat dissolved in bile salt micelles Greatly increases surface area for fat digestion

Pancreatic lipase hydrolyzes triglycerides to free fatty acids and monoglycerides __________________ breaks down phospholipids into fatty acids and lysolecithin Products of fat digestion dissolve in micelles forming mixed micelles Free fatty acids, monoglycerides, and lysolecithin leave micelles and enter

epithelial cells Inside epithelial cells, they are _________________________ into

triglycerides and phospholipids Triglycerides and phospholipids combine with protein to form small particles

called _________________________ Which are secreted into central lacteals of SI villi

Cholesterol and triglycerides from liver form VLDLs which take triglycerides to cells

Once triglycerides are removed, VLDLs become LDLs LDLs transport __________________ to organs and blood vessels

HDLs transport excess cholesterol back to liver High ratio of HDL-cholesterol to total cholesterol is believed to

confer protection against _____________________________

Chapter 19: Regulation of MetabolismNutritional Requirements

Living tissue is maintained by constant expenditure of energy (ATP) ATP derived from glucose, fatty acids, ketones, amino acids, and others

____________________ of food is commonly measured in kilocalories (1 kcal = 1000 calories)

Carbohydrates and proteins yield 4kcal/gm; fats-9kcal/gmMetabolic Rate and Caloric Requirements

Metabolic rate (MR) is total rate of body metabolism = amount of __________________ consumed by body/min

Basal metabolic rate (BMR) is MR of awake relaxed person 12–14 hrs after eating and at a comfortable temperature

BMR depends on age, sex, body surface area, _____________________ level, and thyroid hormone levels

Hyperthyroids have high BMR; hypothyroids have low BMRMetabolism

Is all chemical reactions in body Includes synthesis and energy storage reactions (____________________); and

energy liberating reactions (________________________)Anabolic Requirements

Anabolic reactions synthesize DNA and RNA, proteins, fats, and carbohydrates Must occur constantly to replace molecules that are hydrolyzed in

catabolic reactionsTurnover Rate

Is rate at which a molecule is broken down and ________________________ Average turnover for Carbs is 250 g/day

Some glucose is reused so net need ~150 g/day Average turnover for protein is 150 g/day

Some is reused for protein synthesis so net need ~35 g/day 9 _______________________ amino acids must be supplied in diet

because can't be synthesized Average turnover for fats is 100 g/day

Little is required in diet because can be synthesized from ___________ 2 essential fatty acids must be supplied in diet

Vitamins Are small organic molecules that serve as coenzymes in metabolism or have

highly specific functions Must be obtained in diet because body does not produce them, or does so in

insufficient amounts Can be placed in 2 classes

___________-solubles include A, D, E, and K _____________-solubles include B1, B2, B3, B6, B12, pantothenic acid,

biotin, folic acid, and vitamin C Serve as coenzymes in metabolism

Minerals (Elements) Are needed as _______________ for specific enzymes and other critical functions

Sodium, potassium, magnesium, calcium, phosphate, and chloride are needed daily in large amounts

Iron, zinc, manganese, fluorine, copper, molybdenum, chromium, and selenium are ________________ elements required in small amounts/day

Free Radicals Are highly reactive and oxidize or reduce other atoms

Because they have an ____________________ electron in their outer orbital

The major free radicals are reactive oxygen or reactive nitrogen species NO radical, superoxide radical, and hydroxyl radical

Serve important physiological functions Help to destroy bacteria Can produce vasodilation Can stimulate cell proliferation

In excess can exert __________________________ contributing to disease states Can damage lipids, proteins, and DNA Promote apoptosis, aging, inflammatory disease, degenerative, and

malignant growth Body uses enzymatic and nonezymatic means to protect itself against oxidative

stress Enzymes like ____________________ neutralize free radicals Nonenzymes like vitamin C and E react with free radicals

Regulation of Energy Metabolism Blood contains glucose, fatty acids, amino acids, and others that can be used for

energy _____________________ energy substrates

Control of Adipose Tissue Levels Body appears to have negative feedback loops (an adipostat) to maintain a certain

amount of adipose tissue Adipose cells (adipocytes) store and release fat under ________________ control

And may release their own hormone(s) to influence metabolismDevelopment of Adipose Tissue

Number of adipocytes increases greatly after birth Differentiation promoted by high levels of ___________________

Endocrine Functions of Adipocytes Adipocytes secrete regulatory hormones called adipokines Regulate hunger, metabolism, and insulin sensitivity The adipocyte hormones TNFa, resistin, retinol BP4, and leptin are increased in

____________________ and Type II diabetes Leptin signals the hypothalamus on how much fat is stored, thereby

regulating hunger and food intakeLow Adiposity: Starvation

Starvation and malnutrition diminish immune function Low adipose levels cause low leptin levels

_________________________ cells have leptin receptors Low leptin thus diminishes immune function

Leptin may play role in timing of puberty and in the amenorrhea of underweight women

Obesity Childhood obesity involves increases in both size and number of adipocytes Weight gain in adulthood is due mainly to _________________ in adipocyte size Obesity is often diagnosed by using using a body mass index (BMI) BMI = w/h2

w = weight in kilograms, h = height in meters Healthy weight is BMI between 19 – 25 Obesity defined as BMI > 30 60% of pop in US is either ___________________ (BMI>25) or obese (BMI>30)

Regulation of Hunger Is at least partially controlled by hypothalamus Involves a number of NTs: endorphins (promote overeating), Norepi (promotes

overeating), serotonin (____________________ overeating)Calorie Expenditure of body

Has 3 components: Number of calories used at the BMR make up 60% of total Number used in response to temperature changes and during digestion/

absorption (adaptive ______________________) make-up 10% of total Starvation can lower MR 40%; eating raises MR 25-40% (thermic

effect of food) Number used during physical activity depends on type and intensity

Absorptive and Post absorptive States Absorptive state is ______ hr period after eating

Energy substrates from digestion are used and deposited in storage forms (anabolism)

Postabsorptive or fasting state follows absorptive state Energy is ___________________ from storage (catabolism)

Hormonal Regulation of Metabolism Balance between anabolism and catabolism depends on levels of insulin,

glucagon, GH, thyroxine, and othersPancreatic Islets of Langerhans

Contain 2 cell types involved in energy homeostasis: α cells secrete _____________________ when glucose levels are low

Increases glucose by stimulating glycogenolysis in liver β cells secrete insulin when glucose levels are high

Reduces blood glucose by promoting its uptake by tissuesInsulin and Glucagon Secretion

Normal ______________________ glucose level is 65–105 mg/dl Insulin and glucagon normally prevent levels from rising above 170mg/dl

after meals or falling below 50mg/dl between meals Insulin

Overall effect is to promote anabolism Promotes storage of digestion products ____________________ breakdown of fat and protein

Inhibits secretion of glucagon Stimulates insertion of GLUT4 transporters in cell membrane of skeletal

muscle, liver, and fat Transports by _______________________ diffusion

Oral Glucose Tolerance Test Measures response to drinking a glucose solution Assesses ability of β cells to secrete insulin and insulin's ability to

____________________ blood glucose In non-diabetics, glucose levels return to normal within 2 hrs

Glucagon Maintains blood glucose concentration above 50mg/dl Stimulates glycogenolysis in liver Stimulates _________________________, lipolysis, and ketogenesis

Skeletal muscle, heart, liver, and kidneys use fatty acids for energy