Dec. 7, 2011 REVIEW OUTLINE, FINAL EXAM
This exam will be semi-comprehensive. It will focus on the last lectures --but also earlier concepts/mechanisms that apply to these--such as feedback, anticipation, basic nerve properties (thresholds and integration), hypothalamus, hormone mechanisms (insulin,/glucagon, steroids, etc.), and so on (see below and sample exam).
EVOLVING: Principles--Proximate/mechanistic ("how it works") vs. Evolutionary ("why it evolved") and Teleological (purpose)--be able to apply! Apply to less-than-logical features such as the VERTEBRATE AIR-FOOD tube cross-over!
SELF-REGULATING: Principles &
--HOMEOSTASIS--Key concepts=Negative feedback; variations=antagonistic, behavioral & tonic effectors
--ENHANCED REGULATION-- Key concepts 1. ANTICIPATION (feedforward)--apply to motor cortex in breathing and circulation; and 2. ACCLIMATIZATION: Review EPO in regulating oxygen delivery!!
--REGULATED CHANGE--Key concepts=RESET Systems including
temporary and cyclical work; and POSITIVE FEEDBACK.
Intrinsic vs Extrinsic regulation: know the logic/usefulness of this feature and apply it to this part of the course!
SIZE AND SCALE: how Surface Area and Volume, and their RATIO, change with animal size
Be able to apply Autonomy, Non-maleficence, Beneficence/Paternalism
MACROMOLECULES: WEAK BONDS and INSTABILITY! be able to apply the following concept to effects of TEMPERATURE on life --Many proteins' folds dominated by weak bonds; thus susceptible to perturbations (i.e. are unstable). Why weak bonds? They allow for flexibility for various functions such as binding/catalysis/transport/allosteric regulations. Thus there is a TRADEOFF: many proteins need to be relatively unstable, but thus can be harmed by environmental variation; so internal homeostasis systems evolve to help protect proteins.
GENE REGULATION: the response-element /enhancer and promoter aspects of gene regulation with specific transcription-activating proteins
MEMBRANES and movement mechanisms: know key parts about Diffusion, Conductance and Active Transport
INTERCELLULAR COMMUNICATION --know basic mechanisms of receptor types (2nd messenger and internal receptor), types of signals, same-key-different-locks principle; drug effects (antagonists / agonists)!
THINGS TO REVIEW: --know the basic role of Na+ and K+ in the MEMBRANE POTENTIAL both at rest and during an AP. You don't need to know the details of the gated channel mechanisms, though, but do review the Na/K ATPase!!
--Know the basic mechanisms of NEUROTRANSMITTERS and RECEPTORS at SYNAPSES, and
--BASIC INTEGRATION: how “decisions” to fire occur in integrating neurons.
REVIEW THESE selected examples
1. PANCREAS: From lecture and lab, know full Pancreatic Insulin-Glucagon system!! Apply to ASSIMILATION vs FASTING REGULATION later
i) Anterior pituitary: [Fig 7-10] multistage with Releasing hormones from neuroendocrine hypothalamus neurons go to pituitary, stimulate classic endocrine cells to release tropic hormone which stimulates either target organ or another gland, which releasing a final hormone to target organs. Examples to apply: LH/FSH and TSH for gonads and thyroid, respectively!!!
ii) Posterior pituitary: [Fig 7-9] direct neuroendocrine nerves from hypothalamus release vasopressin, oxytocin!! Apply!
-- Often feedback monitoring of down-line hormones, not always the regulated state itself! Apply to steroid abuse later
REVIEW the role of H+ in RESPIRATION Regulation to apply to ACID-BASE BALANCE later!
DEFENSE: IMMUNE SYSTEMS
Overview: -- New view as a 3rd whole-body regulatory system
A. Functions = Defense from Pathogens ; Clean-up debris; Anti-cancer (own cells gone bad
B. Distinguishing Self vs Non-self
1. Pattern-recogn. receptor proteins (PRPs)-- found on PHAGOCYTES (eater cells) in all animals
2. Defense effector proteins: a) OPSONINS as tags! b) ANTIMICROBIAL Peptides (AMPs) -- how these recognize/kill invaders!
C. Sensors / Integrators / Effectors: organized into TWO systems: INNATE and ACQUIRED
•often individual Cells like LEUKOCYTES (WBCs) & proteins, as well as organs
•communicate with i) cytokines called INTERLEUKINS (IL) and ii) IMMUNOSYNAPSEs
I. INNATE OR NON-SPECIFIC IMMUNITY
A. Barrier TISSUES/ORGANS: 1st Line of Defense; Goal is KEEP 'EM OUT!
-- 1) SKIN + glands (tear/sweat/salivary glands, AMPs: beta-defensins, etc.); resident bacteria
-- 2) RESPIRATORY: mucus w/AMPs —cilia; coughing/sneezing!
--3) DIGESTIVE: mucus w/AMPs; vomiting; stomach acid--how kills; resident bacteria
--4) REPRODUCTIVE: mucus w/AMPs; resident bacteria
HOW resident bacteria benefit 1, 3, 4
B. 2nd Line: Defensives CELLS, Proteins, Regulatory Responses: Goal: kill i) foreign invaders and ii) own cells "gone bad" before they SPREAD
(Neutrophils; Monocytes/Macrophages)--mostly Effectors to kill invaders
---know how phagocytosis works
--2) Natural Killer Cells--innate destroyers of 'bad' body cells that have abnormal proteins on their membranes
--3) MAST CELLS--Integrators of inflammation
--4) Microglia-- BRAIN's own special immune cells --read text
EFFECTOR PROTEINS: Complement series of proteins: 1) act as OPSONINS=tags of foreign objects to signal phagocytes;
2) Act as AMPs -- see Attack Complex in text--make pores in bacterial membranes, cause ion leak with subsequent water osmosis-->pop!
--1) INFLAMMATION: general reaction to attack/injury:
See the steps 1-5 in the figure on the lecture handout, espec. MAST cells as integrators and HISTAMINE and Defense cells; add
--step 6: mast cells, wounded cells release prostaglandins made by COX2 enzyme; these increase blood flow and trigger pain sensors. NSAIDS like aspirin block this!
--step 7: COMPLEMENT effector proteins enter site from capillary leaks
spread, kick in 2 general mechanisms:
--2) FEVER: interleukin-1 (= IL-1) released by active phagocytes goes to hypothalamus=>triggers local prostaglandin [BTW: made by Cox3, which acetaminophen/Tylenol blocks]; this resets the brain's thermostat set-point UP; why this might be useful, but can be bad.
--3) ANEMIA! phagocytes release IL-6 which triggers the liver to put out a hormone that reduces iron in the blood;; why this might be useful from LAB!!
II. ACQUIRED or SPECIFIC IMMUNITY=3rd Line of Defense
A. SELF- vs NON-SELF : Antigens / MHCs
MHC-I as your personal ID receptor on all body cells: naked = let me live; w/antigen =kill me for the greater good (immunosynapse signal to T-cells)
MHC-II as your "military" ID receptor on immune cells-- w/antigen = death warrant signal via immunosynapse w/ T-cells
Tissues/Organs:** Lymphocyte nurseries: thymus, bone
marrow; ** Filters, traps: lymph
and its nodes; spleen;
GALT --know functions of each
C. Defense CELLS & PROTEINS
1) ANTIGEN-PRESENTING cells as SENSORS!
2) INTEGRATORS = Helper T-cells
3) EFFECTORS = a) B-cells and antibodies for invaders; b) Cytotoxic T-cells and killer proteins for own body cells gone bad
B- and T-lymphocytes: have random unique receptors (PRPs-derivatives called Antigen or Ag receptors): how these are based on a Darwinian-like mechanism: i) cannot predict what future invaders will have so ii) randomly generated millions of diff. receptors and iii) Upon invasion, selectively amplify the cell with the receptor that (hopefully) works!! Know briefly how millions of variants are generated with DNA rearrangements and alternative RNA splicing
D. ACQUIRED REGULATORY RESPONSES...
know all steps:
1) ANTIBODY-Mediated SYSTEM: for foreign invaders
Step 1: Sensing by Antigen Presenting Cells!: DENDRITIC cells in barrier tissues (and , in the blood/lymph, phagocytes) eat objects, digest, and display antigens with MHCII; migrate to nodes; "present" to inactive helper-T-cells with correct PRP receptor; also may 'prime' a B-cell with the same receptor
Step 2: Integration: by Helper T-cells are integrators: clone into active helper-Ts and quiescent/reserved memory-Ts; active ones find matching/primed B-cell!
Stp 3: Activate B's: clone themselves into plasma = antibody-making effector B-cells, and into memory B-cells
--Plasma B's secrete Antibodies as soluble versions of Ag receptor; i) Neutralize and agglutinate antigens; ii) Act as OPSONINS--tag for destruction by phagocytes
iii) Phagocytes may also kill by making Oxy. radicals!; iv) Antibody genes HYPERMUTATE to generate even more variations
FEEDBACK SUMMARY -- see handout chart including T-regulatory cells; also DELAY phenomenon and how MEMORY cells help
2) Cell-Mediated System = CYTOTOXIC (killer) T-lymphocytes: kill infected body cells presenting viral, or parasite fragments, or cancer-related abnormal proteins on MHC-I.
Step 1 SENSING: i) DENDRITICs eat Viral-infected cells dying from "bad" proteins; present ''bad" proteins on MHC-II
ii) VIRAL-INFECTED body cell becomes an APC!! Presents viral protein on MHC-I ("sacrifice me" signal). Also CANCER cells may have mutated proteins
Step 2: Integration--Immunosynapse with specific Helper-T [not shown] & CYTOTOXIC-T !!
Step 3: Effectors: CYTOTOXIC-Ts --seek out those bad body cells, make immunosynapse, secrete killer effector proteins (e.g., PERFORINS)
SELF-TOLERANCE: read as
instructed in lecture about why T-cells rarely target our own good cells.
_1) high fever, prolonged anemia.
_2) Allergies: IgE antibodies dock on Mast cells, react to eukaryotic proteins like on pollen, bee toxins…
Positive Feedback inflammation may be lethal (anaphalactic shock)
_3) Autoimmune disease: what is, examples
IV. IMMUNITY and EVOLUTION : 1. Superbugs–reading
2) Male vs
female: latter have better immunity, but also more autoimmune diseases--is this
3) Genetic diversity in immune system--why good
4) Geographical history and harmful traits that AID survival: hemachromatosis example from lab; cystic fibrosis later!
V. NEURO-ENDOCRINE-IMMUNAL INTERACTIONS
--OVERVIEW: integrated approach includes
A. maintenance of water, solutes, osmotic pressure, not just excretion itself; and
B. requires urinary, integumentary, respiratory and digestive systems
C. NITROGEN WASTE: a special problem: why NH3 bad; Liver & Kidney roles
--TABLE of ammonia, urea, uric acid: benefits, drawbacks, uses of each
D. TRANSPORT Epithelia! Why OSMOLYTES needed to move water at molecular level!
a) Salt transp. only: WATERPROOF Epithelia
i) Extrude Na+ w/ Na/K ATPase as an osmolyte
ii) Cl- follows electrically through Cl channel (CFTR !! or ClC)
b) Salt & Water transport:
i) & ii) SAME; iii) Water follows NaCl osmotically through Aquaporins
I. RENAL EXCRETORY ORGANs:
A. Up to 4 universal processes: filtration, secretion, reabsorption, osmoconcentration
B, MAMMALIAN URINARY System--KIDNEY
Nephron: creates RADIAL OSMOTIC GRADIENT ; Parts as follows:
1) GLOMERULUS--Ultrafiltration: sieve-like capillaries: GFR
BLOOD PRESSURE forces through fenestrations; non-selective water/small solutes
2) PROXIMAL TUBULE--Selective Reabsorption/Secretion: active transport of desired solutes
e.g., salt/water transport; Na/Glucose and Na/amino acids COUPLED Transport
3) Nephron Loop [of Henle]--COUNTERCURRENT Multiplier—SEE LAB !!!!
Know roles of each LOOP section, and blood; how results in GRADIENTS and "reservoirs" of salt/urea, and dilute water
--Medulla of kidney: Max. values Human 1400 (<1000 NaCl--can’t process seawater); Kangaroo-rat 5500 mOsm
4) DISTAL TUBULE--more selective reabsorption/secretion--like Proximal tubule
5) COLLECTING DUCT—can be WATERPROOF if need to excrete lots of water, or can be made PERMEABLE with AQUAPORINS if need to REABSORB water and concentrate salt/wastes to excrete.
6) VASA RECTA= blood vessels that pick up water or salt: see below
1) Hypothalamus and ADH (=vasopressin) reflex: a) ON when NaCl high and/or BP low (especially to both deviations): controls collecting duct permeability!! --know aquaporins and how this conserves water, excretes salt/urea; also thirst. B) OFF in reverse situation, so dilute high-volume urine is made
2) GFR autoregulation: how filtration responds if BP changes via the Cardio reflex
3) Cardiovascular Reflex: how responds if volume changes and thus BP changes
4) Heart atrium's ANP reflex: when NaCl high and/or BP high: suppresses blood pressure and proximal tubule salt & water transport, so more salt /water go to the urine
5) JGA’s renin-angiotensin-aldosterone (RAA) Reflex: when NaCl low and/or BP low: all steps leading to restored BP and salt recovery, including salt hunger
BALANCE Concept: input, temporary use/stores in body, output-- must balance
MAJOR FLUID COMPARTMENTS: know ECF, ICF; ECF homeostasis goals:
1. Maintain ICF-ECF osmotic balance to avoid i) hyperosmotic shrinkage & ii) hypo-osmotic swelling
2. Maintain total ECF VOLUME
3. Maintain proper ECF acid/base balance
4. Maintain other ECF chemicals: glucose, Ca, phosphate, etc.;
5. Remove wastes from ECF
Two major strategies at Organismal level:
A. OSMOCONFORMERS, Marine: OCEANS create potential hypertonic stress (1000 mOsm), so most life CONFORMS to this
Most marine organisms use ORGANIC OSMOLYTES: cells accumulate certain organic solutes: small carbohydrates; neutral amino acids; methylamines; urea. Salts are not accumulated because they disrupt proteins, DNA. Except for urea, organic osmolytes have special properties:
i) compatibility = non-disruptive of protein/DNA/RNA function and structure.
ii) counteraction = able to offset some forces that destabilize proteins. Example is TMAO in cartilaginous fishes, which also have Ureas as their main osmolyte, a toxic waste that destabilizes proteins. TMAO stabilizes proteins and counteracts urea [my PhD thesis].
iii) metabolic protection: e.g. TAURINE in many marine non-vertebrates is an antioxidant
B. OSMOREGULATORS: 1. MARINE: these animals are hypo-osmotic and so suffer hypertonic stress; mainly bony fishes on up to mammals. Suffer constant water loss, e.g., via gills of fish. Adaptations:
a. Passive permeability reduction – skin
b. Active Osmoregulatory organs with TRANSPORT EPITHELIA! EXAMPLES: Gills in bony fish; Kidneys in marine mammals; SALT GLANDs in marine birds; Sweat glands
2. FRESHWATER creates HYPOTONIC Stress: animals must osmoregulate; know example of bony fish: gills [& kidney ]
-- 3. TERRESTRIAL: Overview--know paths in and out.
a) SKIN: Problem of “insensible” and sweat losses:
Adaptations for reduction: low-permeability coatings such as wax (insects), dead cell with lipids (mammals). Behavior important as well.
b) Respiratory System: Problem of “insensible” and Panting losses:-- why lung air is 100% humid
How a NOSE "countercurrent" helps--cools off as it moisturizes incoming air, captures outgoing moisture by condensation
c) Osmoregulatory Organs: INTESTINES—how small intestine moistens food and large intestine dries it out
d) Osmoregulatory Organs: KIDNEYS—see earlier material
ANHYDROBIOSIS = SPECIAL Adaptation to extreme Desiccation:
--know Examples of organisms which survive this; & MECHANISM: not all known; but know how TREHALOSE helps !
C. OSMOConforming within Osmoregulators
1. Cholera, other Diarrheal Diseases: role of cholera toxin on gut
2. DIABETES—see INSULIN-GLUCOSE lab
3. Urinary tract infections: bugs may steal organic osmolytes from kidney/urine to survive salt/urea
4. Cystic Fibrosis: most common genetic birth defect in European Caucasians
--mutated Cl CFTR channels; example of gut salt/water transport--know mechanism and mutation
EVOLUTION—CFTR mutant may protect from tuberculosis—how
Overview: common causes of too much or too little H ions:
TOO MUCH: Metabolic production such as CO2, lactic aced; Respiratory syndromes such as emphysema; Environmental CO2 as in current oceans
TOO LITTLE: Metabolic loss via ammonia, vomiting; Respiratory syndromes such as hyperventilation; Environmental alkalinity such as alkaline lakes
1. LOCAL fast REGULATION = BUFFERS: how certain weak acid/bases use Mass Action to reduce (‘buffer’) changes in pH. Know key buffers in ECF and ICF
2. NEURAL medium-speed REGULATION = RESPIRATION in response to pH changes in the blood—how this works!
3. KIDNEY long-term REGULATION: how proximal tubule can secrete excess acid or base
Evolution: From intracellular lysosomes (specialized organelle) to extracellular in invaginated chamber that became specialized organs
STAGES: Ingestion, Storage, Digestion, Absorption, Defecation; later—Assimilation (then Fasting)
DETAILS on DIGESTION: Extracellular Enzymes from salivary glands, stomach, pancreas/small intestine
=HYDROLASES: Unused energy (except heat in endotherms): X-Y + H2O ---> XH + YOH + heat
a. Carbohydrases polysaccharides=i) 1,4a Starch, Glycogen ii) 1,4ß Cellulose, Chitin
-->breakdown to Monosaccharides, e.g., glucose. Why cellulose, chitin so hard to digest!
b. Proteases/peptidases:--> to free amino acids
c. Lipases: triglycerides, phospholipids, waxes-->to fatty acids, monoglycerides, glycerol, etc.
DIETARY INPUT: need
1. MICRONUTRIENTS: vitamin/minerals--see Iodine, Vitamin C, D reading
2. MACRONUTRIENTS-- i) CARBOHYDRATES ii) PROTEINS iii) LIPIDS--highest E content: why?
Need for both ENERGY and BUILDING BLOCKS: e.g. triglycerides vs cholesterol/P-lipids
READING--human evolution and lipid needs: DHA in brain development/evolution
II. ORGANS: know those typical of vertebrates
A. MOUTH: Ingestion and often Digestion with saliva: know main events; amylase
B. Pharynx, Crop, Esophagus: general roles
C. STOMACH: Storage sometimes; DIGESTION: Churning, pumping; Specialized Exocrine-gland secretions:
1. HCl: stomach: know functions of immunity and protein unfolding
2. Acid-resistant acid-activated enzymes such as pepsin(ogen), primarily for protein digestion
D. PANCREAS: Aids DIGESTION with exocrine secretions:
1. NaHCO3: pancreas—know function and EQUATION to neutralize HCl; 2. Enzymes: all types including lipases
E. LIVER, GALL BLADDER: Aids DIGESTION with exocrine secretions
BILE = glycocholic acid from cholesterol: liver/gall bladder: emulsifies by being amphipathic (hydrophilic and 'phobic)—how this breaks up droplets, helps lipase
F. SMALL INTESTINE: Digestion and ABSORPTION:
1. HIGH S.A. = folds, villi, microvilli
2. UPTAKE a. Endocytosis: some proteins, peptides: role in antibodies in infants
b. AAs, glucose: Transport including coupled: how Na+ gradient can pull in glucose, AAs against gradient
c. FAs, glycerol: Diffusion then Biosynthesis back to TGs (triglycerides) + Exocytosis:
CHYLOMICRONs-->WHY these lipid-protein droplets need to be made to control lipid delivery!
G. LARGE INTESTINE –Digestion (bacterial/archael-aided) in some species; Absorption of salt, water, vitamins; DEFECATION
III. REGULATION: Local / intrinsic: ENTERIC NERVOUS SYSTEM
Extrinsic: roles of adrenal gland, para- and sympathetic nerves!
--1. Stomach:--how LOCAL ENS reflex works to activate HCl, enzyme glands as needed. How extrinsic brain can activate in ANTICIPATION to reduce delays…or suppress for fight-or-flight
--2. Small Intestine: how LOCAL ENS reflex loops work to activate CCK to coordinate bile and pancreatic-enzyme release with fat coming in; CCK as SATIETY signal
IV. ASSIMILATION vs V. FASTING
Decisions to make after a meal: USE absorbed food for:
A) ENERGY: 1) Immediate use (ATP); 2) Energy STORAGE for future
B) BUILDING BLOCKS: Repair/Growth/Reproduction
C) 3rd Option: “Burn off” excess calories as waste heat (LATER!)
by PANCREAS: INSULIN-GLUCAGON !!
-->REVIEW key steps of this system and ALL effectors (Liver, Adipose, Muscle) regulated
IV. ASSIMILATION: see big flow charts in lecture for AAs/Glucose and for Lipids!!
1) Immediate: ATP for LIVER then OTHER cells
2) If Extra: Glycogen storage: Liver, muscle, glia
3) If more Extra—liver: converts to triglyceride repackaged as VLDLs to send to ADIPOSE storage
B) Amino Acids:
1) building blocks: make own proteins in liver and then all other cells, esp. Muscles
2) Extra--Immediate Energy (cell ATP)
3) Even more Extra--Storage: some extra can be converted to glucose/glycogen or
4) triglyceride by the liver; repackaged as VLDLs
C) Chylomicrons, VLDLs: see new figure 9-4!!
1 a) Storage: TG energy lipids from these taken up, stored in ADIPOSE
1b) Structural lipids = P-lipids and cholesterol from chylomicron remnants re-packaged in liver as VLDLs with TGs made from excess glucose/AAs. After adipose extracts TGs, Vldl's become LDLs which supply all cells with P-lipids and cholesterol for making membranes; by gonads to make sex hormones. HDLs take excess back to liver for conversion to bile
V. FASTING: use STORED energy
1) Adipose Tissue: immediate energy!
Triglycerides broken down to fatty acids & glycerol into blood [with albumin carrier proteins] for all non-neural cells. GLUCAGON signals this
2) Liver, Glial cells:
a) Glycogen broken down to blood glucose for nerves’ immediate energy (nerves cannot use fatty acids) . GLUCAGON signals this
b) Starvation -- Liver can convert fatty acids to ketones for brain fuel; CORTISOL signals this
3) Muscle Protein only broken down only during starvation, into amino acids converted by liver into glucose can be used for immediate energy (espec. neurons). Mainly due to CORTISOL
LAWS of THERMODYNAMICS: dominant principles
B. The ANIMAL ENERGY EQUATION--know definition of each:
*BMR or BASAL Metabolic Rate--minimum work to stay alive at rest against entropy
*DIT: Digestive for processing food; Regulatory for "burning off" excess calories
*ACTIVITY: voluntary EXERCISE; involuntary N.E.A.T. (fidgeting, etc.)
*PRODUCTION: growth, energy storage, reproduction (only component with net increase in order)
C. EVOLUTION-- Species and Individual Differences: 1990s Breakthrough: ob/ob mutant obese mice & the ANIMAL ENERGY EQUATION:
ON SAME DIET = same Efood Input
Abberation or Evolutionary Adaptation? Lean vs. Heavy Animals in Nature
Concept of ADAPTATIONS to different habitats
-- Lean “agility” adapted: more agile for getting food/avoiding predators: good if food not scarce for long periods. BUT: Suffer (die) during famines and prolonged illnesses
--Heavy/Famine adapted: survive better in feast-famine habitats; BUT: suffer obesity side-effects if food becomes plentiful: already happening to marmots in ALPS!!
Humans: study groups (Pimas, Polynesians)—how their ancestry probably explains patterns
How is overall energy balance achieved? Insulin/glucagon do not explain equation's INPUT vs OUTPUT regulation
--1994 breakthough: Ob gene codes for LEPTIN: a long-term signal of fat reserves, suppresses appetite when reaches set pt.
Appetite Centers (Satiety and Hunger)
INPUT: Increase /Reduce by controlling APPETITE/HUNGER & EATING
OUTPUT :Raise or lower by controlling
i) BMR via THYROID gland /Thyroxines; ii) DITregul via BROWN adipose tissue; iii) Activity espec. N.E.A.T.
i) LEPTIN from adipose cells
Since Leptin -- many more signals found -- New text Table 15.2 and Fig 15-6
•GHRELIN: hunger signal made by empty stomach!
•CCK: satiety signal from sm intestine sensing fats
•COMMAND signals of Hypothalamus discovered , e.g., POMC/melanocortin/MSH signaling
ENERGETICS of LEAN PEOPLE (compared to obese):
i) higher BMRs; ii) higher DIT through Brown Adipose Tissue: how this works!
iii) may have more Activity like NEAT fidgeting; iv) net result is lower PRODUCTION (body mass)
: know some key Digestive manipulations such as fake food (Nutrasweet). Why these don’t work well. Know some new tests to fool the ENERGY signaling system (e.g., Ghrelin vaccine, leptin injections).
OVERVIEW: Closely related to Energy since most metabolic energy becomes heat! Know deltaG plot!
A. BASIC TEMPERATURE EFFECTS:--Rate effects vs denaturation: how these yield optimum
B. THERMAL OPTIMA: examples of different organisms and definitions of ECTOTHERMS, ENDOTHERMS, HETEROTHERMS
How optima can evolve or acclimatize:
1) HOMEOVISCOUS Membrane Adaptation: membrane needs to be semi-solid; tradeoff between fluidity vs thermstability; how saturation of phospholipids (fatty acid tails) works at different temperatures; changed by saturase, desaturase enzymes. Role of cholesterol
2) PROTEIN Optima: like membranes, these change by #weak bonds, disulfide bonds, etc. but not usually within lifetime (requires mutations, natural selection). How this helps protein function in tradeoff between optimal flexibility vs thermostability
C. HEAT EXCHANGES/BALANCE: 1. BALANCE: Input (ecto or endo) = output! equation: Hbody = Hmetab. - Hevap. + Hconduc. + Hconvec. + Hradiat.
2. 4 ways to regulate: 1) Gain external; 2) Retain internal; 3) Generate more internal; 4) lose excess
3. Exchanges: see diagram 15-12
D. , vertebrate: SEE new TEXT 15-20 and LAB diagram for hypothalamus
Basic negative feedback (sensors, hypothal., effectors) used in ectotherms + endotherms!
I. ECTOTHERMS: deltaHmetab = not much, although it exists! External H dominates
A. ADAPTATIONS --What happens if Environmental Temp. not at OPTIMAL body Temp:
1. Full POIKILOTHERMY: Tbody = Tambient =No thermoregulation; store food for inactive period
--all microorganisms, most fungi, most plants, many vertebrates, many invertebrates
a) DAILY: slow at night due to kinetic effects, optimum evolved for day temperatures
b) SEASONAL: dormancy to save energy: “hibernating” frogs, insects underground
Some may have Biochemical Compensation: much unknown
a) Membrane Homeoviscous Acclimatization: mainly seasonally, but some plants alter membranes daily
d) Make more enzymes in the cold
d) Isoforms: winter or summer set of genes for related enzymes with different optima! seems to be rare
e) ANTIFREEZES: special proteins or solutes
f) Heat SHOCK proteins for large rapid change [e.g. sudden 5 or 10o jump]: HSPs made, protect others from denaturation but only temporarily
2. Ectothermic Regulation: some insects, reptiles, fishes, etc.
Recall Hbody = [Hmetab ] - Hevap + Hcond + Hconv + Hrad
a) DAILY: bask, seek shade; Vasodilate or constrict; pant; etc.
b) SEASONALLY: migrate to favorable thermal habitat
--mostly behavioral: graph of lizard's body temperature!
II. ENDOTHERMS: Hmetab is dominant
EVOLUTION: examples of certain plants, insects, fishes (most are ectotherms though); Birds and mammals of course
--Requires high AEROBIC metabolism: red muscle; high BMR; special heater organs
Advantages: easier to achieve homeothermy over wide range; constant high diffusion etc.;
Disadvantages: high cost—know graph of MR with temperature
--BMR scales with body mass! See also LAB and Surface Area/Volume Hypothesis for heat : what is, why it has PROBLEMS!
** NEW hypothesis in READING (TEXT BOX!)
ADAPTATIONS--What happens if Environmental Temp. not in OPTIMAL “neutral zone”:
A. THERMOREGULATE -- for ACHIEVING HOMEOTHERMY:
1. GAINing external: Ectothermic Gains (like reptilian ancestors):
a) basking behavior; etc. b) anatomy to absorb sunlight
2. RETAIN internal better= trap Hmetab & reduce losses
a) Vasoconstriction: arterioles, shunts/bypasses regulated by hypothalamus via sympathetic nerves
b) Insulation: adipose, feathers, hair; Behavior--nests; huddling; burrows
c) Behavioral insulation: huddling, burrowing, nest building…
e) Countercurrent exchangers: retes and how they work; know 1 example
3. GENERATE more Hmetab in cold: waste energy
a) SHIVERING –red (SO) muscle ATP without kinetic work: 100% of ATP into heat; usually aerobic
b) Non-shivering Thermogenesis:
i) BMR and Thyroid: Hypothalamus-TRH-TSH-THYROID-Thyroxine: thyroxines may open mammalian Na+ leak channels: cells “waste” ATP by "bailing" out Na using the Na/K ATPase. May also open UCPs (UNCOUPLING PROTEINS). Main organs = kidney, liver; muscle, adipose,
ii) BROWN ADIPOSE TISSUE: Mitochondrial Futile Cycle: burns lipids without making ATP with UNCOUPLING Protein UCP!
Normal: Lipids--->NADH--->Elec. Transport + O2--->H+ gradient---> ATP,
B.A.T.: special gated H-channel (UCP-1 or thermogenin) that dissipates H+ gradient--->heat, no ATP
B.A.T. found in hibernators (used in springtime); mammalian neonates in general; lean adult humans??
4. LOSE Excess H: most present in ectotherms too
a) Reduced insulation—e.g. shed hair
b) Vasodilation and lose Hrad/cond/conv
c) Enhanced Evaporation! sweat, pant: know how overall deltaG is negative even against heat gradient!
d) Countercurrent coolers
—Oviparous, ovoviviparous, viviparous
A. Anatomy: Development—how tubercle, folds, swellings change in males, females; role of Y chromosome
ADULT: review if necessary; 1990s findings on 'hidden' clitoral anatomy
B. HORMONE Physiology: 1. Steroid hormone synthesis & receptor mechanisms: review if necessary
2. SEX STEROIDS in both genders: know roles of estrogens, testosterone, progesterone
A. Sperm Production & Regulation: seminiferous tubules from LAB: constant march of cells inwards to form sperm. Sperm features=tail, midpiece, nucleus, acrosome. Recent controversy: killer & blocker sperm
--Regulation: basic negative feedback from hypothalamus: GnRH, LH/FSH, sperm devel., testosterone. How ANABOLIC testosterone agonist steroids affect this system and WHY!
B. Mating: Intercourse, Ejaculation, Orgasm: positive feedback loop via the spine, modulated by higher extrinsic centers; goal of getting sperm into uterus
A. Ovum Production & Regulation: cycles more complex; much fewer ova produced in lifetime
1. FOLLICULAR phase: First days of cycle: negative feedback through hypothalamus-->RH-->pituitary-->LH/FSH-->ovary: ovum development and follicles-->estrogen (+ testosterone)-->2Ż sex characters including uterine lining growth and neg. feedback to hypothalamus= steady development of follicles and oocyte
2. OVULATORY phase: Day 10-12: ovum mature! Hypoth. begins to switch to positive feedback: more estrogen--> more RH-->more LH/FSH-->more estrogen. Thus get burst of LH which causes ovulation at day 14 of mature ovum
3. LUTEAL Phase: Day 15-on: remaining follicle cells become corpus luteum, a gland which makes progesterone. This hormone shuts off hypothalamus repro. center, so no new eggs start, and makes uterine lining thicker.
4. Day 28: if no pregnancy, corpus luteum dies just before Day 28; so progesterone declines, and a) Lining is lost= menstruation; b) hypothalamus turns on again, start over at step 1 above.
B. Mating: Intercourse, Orgasm: positive feedback again; goal of getting sperm into uterus
C. Fertilization & Pregnancy: if embryo present-->makes CG which keeps corpus luteum alive
D. PARTURITION (Labor & Birth)
1. Fetus LUNG matures to give signal? triggers inflammatory response? => Cervix dilation begins.
2. Stretch sensors in cervix detect & signal mom’s hypothalamus to start positive feedback reflex: hypothalamus releases oxytocin (neurohormone) via pituitary; this stimulates uterine contractions so baby's head pushes on cervix, dilating/stretching it more, which again signals hypothalamus via stretch sensors to release more oxytocin. . --->Birth!! (eventually)
Lecture #31: --RESURRECTED Protein is important why?
--STOP THE KILLING --why are our resident bacteria good and what are we doing to them?
Lecture 32: --SKIN's IMMUNE: what is this new finding?
--SPECIALIZED REGULATORY T CELL does what?
--WOMEN HAVE STRONGER: what is the possible new reason w/microRNAs?
Lecture 33: --BOUT of TERROR does what to immunity?
--THE HYGIENE HYPOTHESIS says what about modern cleanliness?
--VACCINE FOR NICOTINE--Ag receptors/antibodies normally cannot recognize small molecules like nicotine. How did they get around that?
Lecture #34: --MYTH: YOU NEED TO PUSH FLUIDS: why is the 8-10 glasses-of-water-per-day possible bad advice?
Lecture #35: --THE INNER MYSTERY; briefly, what is NOT understood about the nephron concentrating mechanism?
--GROWING ORGANS: what did Tengion accomplish?
Lecture #36: --UNANSWERED QUESTIONS--what is the mystery and one possible answer?
--THE SHAPE OF A NOSE--helps how? Examples?
--My Papers . . show what about osmolytes?
--SURVIVING SALT AND UREA -- how does the kidney medulla do it?
Lecture 37: --TREHALOSE: AN INTRUIGING: how does it work? Some applications?
--GROWTH OF E. COLI in URINE: how?
--OSMOLYTES CRITICAL TO SURVIVAL -- how do they help the kidney?
-- CYSTIC FIBROSIS articles--what is CF, role of wild-type gene, and why the CF mutated gene may persist
Lecture 38: --WORRYING LEVELS OF IODINE--the US adds Iodine to table salt, not so in the UK. What is the result? From text: why Iodine needed?
--FISH and NO CHIPS: what is DHA (docosahexanoic acid)'s importance? Sources? Role in evolution of brain size?
--JACK OF ALL TRADES: why is Vit D so important & how do we get it?
Lecture 39: --diagrams!
--THE EVOLUTION of LACTOSE TOLERANCE: what do these studies show?
--STOMACH's SWEET TOOTH--briefly, what are some new findings on 'taste buds' in the gut?
Lecture 40: --OBESITY and DIABETES: what is the "thrifty gene" hypothesis, role in the Pima Indians, etc.
--FAT CHANCE: long article on BROWN FAT: how does it relate to energy balance?
--A FEW UNIQUE WAYS: what is NEAT and ways to enhance calorie burn-off?
Lecture 41: --my new chapter excerpt to reinforce lecture; know 2 examples of current GLOBAL WARMING effects on animals
--OBESITY's MATCH: what is Denmark doing and why?
Lecture 42- 43: I will put big ASTERISKS/STARS on key articles.
KIDNEY/OSMOREGULATION /IMMUNE lab: how urine output is
METABOLISM LAB: material to support lecture: Scaling, its meaning; ectotherm differences
DIGESTION Lab: function of BILE
TEMPERATURE LAB: how sweating deltaG works; the HEAT Equation; hypothalamic thermoregulation system!