Oct. 27, 2011
You may need to review the first lectures' basic concepts & mechanisms, used ALL SEMESTER!
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.
HIERARCHY OF REGULATION
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
Principles: Be able to apply Autonomy,
Non-maleficence, Beneficence/Paternalism and Justice
MOLECULAR & CELLULAR PHYSIOLOGY
MEMBRANES: know key concepts 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 ([ant]agonists)! And GAP JUNCTIONS!
REGULATORY SYSTEMS: Review
basic roles of Endocrine and
Nervous systems as they apply to the systems below; e.g., parasympathetic vs. sympathetic, roles of hormones and neurotransmitters.
-- ALSO UNDER NERVOUS SYSTEMS: review how synapses and receptors work ; especially review the O2/CO2/H reflex and how it is regulated by ANTICIPATION by the motor cortex!
-- ALSO UNDER ENDOCRINE SYSTEM: review how hypothalamus-pituitary system works
SUPPORT/MOVEMENT: MUSCULOSKELETAL Systems
I. SKELETAL MUSCLE (Striated)
A. Structure: 1) Organ [and Fascicles]; 2) Fibers=multinucleated Cells; 3) Fibrils=organelles; 4). Sarcomeres with highly organized filaments, alpha-actinin-disc to anchor them;
5) Proteins filaments a) THICK = myosin in bipolar array: myosin head structure, titin as anchor and ? 2 binding sites for ATP, actin; b) THIN = actin,tropomyosin,troponins
----6) Transverse tubule (TT) & 7) Sarcoplasmic Reticulum (SR): arrangement, uses
B. MECHANISM: RESTING: Tropomyosin blocks myosin from binding actin : know molecular arrangements!
CONTRACTING: synapse with ACh nicotinic receptor lets Na+ in; APs go down T-tubes; & SR Ca++ channels open; Ca++ conducts in, binds to troponins, flip tropomyosin out of the way; myosin head binds to actin = crossbridge; head does power stroke; head disconnects using ATP, which then reenergizes the head. REPEAT the myosin steps until:
Relaxation: Ca++ ATPase pumps remove Ca++ back into SR; troponin/tropomyosin flips back to blocking position
Details on powerstroke: ATP use in detaching/energizing myosin; one-way aspect of bipolar myosin filament; why relaxation slower than contraction; RIGOR MORTIS
C. NEURAL CONTROL: LAB!
--1. AP frequency (not used much for reg) controls twitch or tetanus: how tetanus is a normal function or disease
--2. MOTOR units provide main mech. For graded contractions; HOW this works
D. ENERGY: know all pathways and ATP roles!! Intrinsic fuels 1) Creatine-phosphate + 2a) muscle glycogen. External extrinsic fuels = 2b) liver glycogen, e) adipose fat
-- Anaerobic vs. Aerobic uses!!! CP, intrinsic glycogen give fast energy with minimal diffusion time; but burn out quickly due to low energy yield
--liver glycogen and fat give long-lasting energy, but are slow due to distance to travel (and long breakdown pathways for fat) and oxygen delivery/diffusion limit
E. FIBER Specializations: compare three main types; use TABLE from lecture/text
Physiological Genomics--Know the 4 types of myosin genes given, their uses and expression in different animals!! E.g., IIb vs IIx
Fast Glycolytic (FG or IIx in humans, or IIb superfast in rodents); Fast Oxidative/Glycolytic (FO or FOG or IIa); Slow Oxidative (SO or I): --how each differs in color, energy adaptations, usage & fatigue resistance; External energy sources for SO, local glycogen for FG
FATIGUE: causes besides fuel depletion? Lactic/Pi poison Ca-ATPase!! Also may inhibt myosin, glycolysis
USAGE: Evolutionary adaptation of Fibers: a muscle organ can have up to all 3 types, depending on adaptive use. Some Examples to ponder: bottom fish; grazer (cow); wild migrators vs domestic birds; halibut vs tuna;
--Humans: limb muscles are mixtures of all 3 types, but vary by athletic styles/training: sprinter vs marathoner!
F. Endocrine Control: 1) ENERGY temporary RESET: epinephrine boosts muscle glucose via GPCR cAMP amplification
2) SIZE : GH/IGF vs MYOSTATIN
3) Fiber Types: USAGE and CHANGES: what happens during various types of training to fiber types;
G. MECHANICS: from LAB! 1. tendons, ligaments as springs; 2. How antagonistic muscles work, and 3. LEVERAGE for speed or force
II. CARDIAC MUSCLE--has sarcomeres, but not multinucleated; has gap junctions
III. SMOOTH MUSCLE: no sarcomeres; meshlike, alternating actin/myosin filaments for churning/squeezing etc.
OVERVIEW--Basic Life Maintenance Processes:
Life must obtain and transform energy and matter into "self"
1) obtain energy & raw materials 4) use for biological work
2) circulate/distribute around organism if necessary 5) release wastes = unusable (HEAT) & materials
3) transform into ATP, energy storage & bldg blocks 6 )Defend from predators and pathogens
OVERVIEW --A. FUNCTIONS
of Pump, Vessels and Fluid
_1. Bulk Transport--overcome slow diffusion & conduction: •of molecules; •of heat; •of cells--immune, red, etc.
_ 2. Force transmission--worm locomotion, spider jumping, clam burrowing; genital erection; renal filtration pressure
B. OPEN vs CLOSED Systems: difference and examples
C. Three Possible Components: Fluid, Pump, Tubes
HEMOLYMPH (if no vessels)
A. Plasma: water, salts, plasma proteins (antibodies, complement, albumin, etc.); nutrients; etc.
B. Cells = erythrocytes, leukocytes, thrombocytes/platelets: basic roles.
--CLOTTING: how arises as positive feedback reaction to plug and seal a wound!
II. PUMP =HEART or CARDIAC component
Evolution of "heart" types:
1. Extrinsic muscle pump: e.g., veins with one-way valves squeezed by skeletal muscle
2. Peristaltic: how works
3. Chamber: classic heart with one-way valves. Vertebrate heart: evolved from 2 to 4 chambers; why!
STRUCTURE/FUNCTION: Mammalian details:
A. Heart structure 4 chambered with 1-way valves; know mammalian details!!
B. Heart's Pump Cycle--chamber pump has 2 PHASES (see lab!! KNOW ECG and what it measures):
---a. SYSTOLE -- electrical events starting with SA Node pacemaker --conducts in specialized fibers via gap junctions
C. CARDIAC OUTPUT: CO = HR x SV!!!!
D. Intrinsic Regulation:
-- a. HR AutoRegulation: autorhythmic pacemaker cells have built-in Ca-channel leak; fires 1/second roughly
-- b. SV AutoRegulation: if heart fills more from veinous return, heart automatically contracts harder
E. Neural extrinsic Regulation: Barostasis Reflex
Barosensors/chemosensors in arteries; Medullary cardiac integrator; sympathetic / parasympathetic nerves to heart.
III. VESSELS = VASCULAR
A. EVOLUTION: 1. SERIES and PARALLEL flow patterns!--SERIES flow for Lungs (pulmonary) at low deltaP, then to Main body (Systemic) at high deltaP with PARALLEL flow: why this arrangement important
2. Systemic vs. Pulmonary evolution: what this dual-heart dual circulation split is all about; why fish don’t have this and we do
1. FLOW LAW (Poiseulle-Hagen Law): FLOW F = (P1 - P2) / R where R is proportional to viscosity, length, and inverse of radius to the 4th power; Also GRAVITY creates backpressure P2.
VIDEO: why high pressure and low pressure
both are bad. NOTE: since FLOW (F) in the total circulation is the CO, the
equation is CO
= deltaP / R !!!!!!
2. VELOCITY LAW: Vel = Flow/(Pi x r-squared) !! That is, velocity decreases if total area of tubing increases!
C. STRUCTURES & FUNCTIONS:
1. AORTA/ARTERIES: a) Rapid delivery system: a few wide tubes= r high for each, but total Pi x r-squared low
--- b) Pressure storage/release: using elasticity! how this is used, why needed!
2. ARTERIOLES--a) Valve System -- Variable sphincters for REGULATION: controlled by extrinsic nerves, hormones, and intrinsic chemicals; valves change Resistance b) Metarteriole bypasses
3. CAPILLARIES: a) VALVES again: precapillary sphincters =--for Intrinsic REGULATION. Know local factors that dilate, constrict these
---b) Slow exchange system--many
narrow capillaries: r is small for each; BUT total Pi x r-squared high so flow slows!!!!!!!!!
4. VENULES & 5. VEINS: a) rapid return system: a few wide veins= r high for each but total Pi x r-squared low;
---b) Auxiliary pumping with extrinsic muscles and one-way valves!! --NOTE varicose vein problem in humans
6. LYMPHATIC Veins: how lymph fluid forms via capillary leaks; what are its functions; how residual fluid returns to blood/heart
---capillary leakage occurs most places, except at blood-brain barrier and at lungs.
IV. Integrated CARDIOVASCULAR Regulation
Pressure/velocity DIAGRAM; how P changes, crucial limits and mean; why P drops at arterioles/capillaries, necessitating high systemic deltaP. Think about why high deltaP isn't necessary to drive same CO through the pulmonary system!
MAIN GOALS: see lecture
and lab supplement on GOALS for C.O.
(#1 priority) during Rest and Exercise; GOALS for pressure not being too high
or low (#2 priority); the role of R
1. Resting -- BAROSTASIS Reflex: recall the negative feedback responses and parts (sensors, integrator, effector) and NTs for homeostasis using sympathetic, parasympathetic neurons, Cardio. center in medulla of the brain
2. Exercise: know Resting vs. Activity differences in deltaP = CO x R: example numbers, be able to apply!!! OVERALL effect in exercise is reduced R, higher CO, modest deltaP change! Apply this to your lab results on human blood pressures and exercise; know why this is all important.
REGULATION: -- a) Intrinsic: i) Heart SV increases due to venous return; ii) precapillary and arteriole sphincters dilate with local chemical changes--BLOOD pH/gases
-- b) Extrinsic NEURAL Regulation: Anticipation by MOTOR Cortex: activates Cardiac Reflex Integrator; sympathetic system with synapse and NE works before exercise depletes O2: C.O. raised. Simultaneously, Gut arterioles constrict due to more NE at synapse.
---c) Extrinsic Endocrine system: epinephrine anticipation— travels via blood to dilate muscle arterioles and boost CO (heart) even more
1. Hypertension from high peripheral R: obesity; atherosclerosis; high salt; 90% unknown
--think about why, if R is too high, does deltaP go up instead of C.O. going down (which would keep the pressure from damaging you)
2. Fibrillation: due to blockage in coronary arteries OR damage to conducting fibers: CO plummets
RESPIRATORY SYSTEMS: GASES
2 Processes (DIFFUSION, BULK TRANSPORT) in 4 possible STEPS :
1. Breathing (bulk transport); 2. Gill/Lung-to-Blood Diffusion; 3. Circulatory (bulk) Transport; 4. Blood-Cell Diffusion
PROCESS 1=DIFFUSION: Diffusion LAW (Fick's): Q= A * D * (P1-P2)/deltaX for gases!
Why partial pressures
are necessary due to low solubility in water
PROCESS 2=BULK TRANSPORT: breathing, circulation organ pumps evolved. For breathing, what are the key problems facing aquatic and air breathers, and their basic adaptations?
THE 4 STEPS:
Step 1. BREATHING =EXTERNAL BULK TRANSPORT
A. MECHANICS: 1. Passive: examples
--2. ACTIVE: PUMP mechanisms:
---a. TIDAL--large insects; most land vertebrates. Imperfect: limitations of time (can’t be continuous due to exhaling), and have dead space mixing of fresh and stale air/water.
----Evol. glitch: Air/Food Crossover: reading on this basic vertebrate flaw
---b. FLOW-THROUGH: most efficient because no mixing of new/stale water, and continuous flow is possible (e.g. ram ventilation); some fish(>90% efficient in getting oxygen); birds are about 40% due to mixed Tidal and Flow-through. Mammals about 25% efficient in getting oxygen
B. Vertebrate REGULATION:
--1. Extrinsic NEURAL: Resting homeostasis with anticipation by motor cortex: know all sensor/integrator/effector parts from lecture, lab. Role of sensors; O2 as a weaker signal than CO2 -produced H+ --know EQUATION for this!!!
--2. Extrinsic ENDOCRINE: Stress: what epinephrine does to airways
Step 2. DIFFUSION : GILL or LUNG<-->BLOOD:
Diffusion Law: How each part of the equation has evolved ADAPTATIONS, needed due to the slowness of diffussion:
--1. Adapting A: Surface AREA--folds such as alveoli, gill lamellae
--2. Adapting D: higher body T
--3. Adapting delta-x: thin barriers--lung alveolar EXAMPLE!! Be able to draw
--4. Adapting P1-P2: a) Ventilation=breathing rates keep alveolar P1 for O2 high, P2 for CO2 low.
--------Perfusion: increase blood flow to keep blood P1 for CO2 high, P2 for O2 low
---c) Convert gases to/from non-diffusible form: HEMOGLOBIN: HbH4+ + 4O2 <-->4H+ + Hb(O2)4
----- CO2: convert to/from non-diffusible forms as Hb-CO2, and CO2 + H2O<--> HCO3- & H+ with carbonic anhydrase
Step 3. CIRCULATION
A. O2 Transport : 1. Dissolved gas (1-2%) & 2. Bound to Hb (98-99%, mammals)
-- a) Structure/Function: heme with iron (Fe), large protein to modulate Fe electrons by T-R shift! Function = O2 BINDING/RELEASE FUNCTION by T-R shift and COOPERATIVITY
---- differences of T (tense) and R (relaxed) conformations; R favored by high #O2 collisions; how O2 delivery works with this effect and with cooperativity of subunits affecting each other!
---- Purpose of sigmoidal curve=better loading/unloading over physiological oxygen range in comparison to ordinary protein: compare function & plot to MYOGLOBIN, an 'ordinary' binding protein
---b. Bohr effect: how pH aids delivery!
---c. Resp. POISONS: CO (carbon monoxide) problem! know why dangerous, why not smelled, why O2 loss not sensed so you get no warning!!
REGULATION: a) SPLEEN! Clean up dying RBCs and Reservoir for diving-- know both roles and in what mammals! b) NEURAL: medulla
reflexes, motor cortex coordinate circulatory pumping and breathing
c) ENDOCRINE REGULATION: i) epi also alters circulation, respire together; ii) EPO!
B. CO2 Transport: 3. Dissolved Gas = mammals 5%
--2. Bound to Hb=mammals 25% . Binds to N-terminal amino acid, NOT to the Fe/heme
--1. HCO3- + H+ =mammals 70% --ROLE of CARBONIC ANHYDRASE in RBCs
DIFFUSION: BLOOD <--> CELL
-- 1. Adapting A: Surface AREA by high density of capillaries
-- 2. Adapting delta-x: narrow, thin-walled capillaries
-- 3. Adapting D: higher body T ;
-- 4. Adapting P1-P2: a) Perfusion=circulatory flow keeps blood P1 for O2 high, P2 for CO2 low.
---- b) Release O2 from non-diffusible form: HbO2 releases O2; Cellular globins help (below)
---- c) Convert CO2 to non-diffusible form: Carbonic Anhydrase makes HCO3- which won't go back to tissues; some CO2 binds to Hb too.
CELLULAR GLOBINS help take O2 out of blood to store, then release inside cell in severe O2 depletion: myoglobin, neuroglobin!!!
CO2 + H2O<--(via CA = carbonic
anhydrase)-->H+ + HCO3-
FROM LABS: know especially these to reinforce lecture:
MUSCLES: twitch vs tetanus; motor units!
lecture on pressure dampening and hemodynamic equation (∆P = C.O. x
R -- resistance effects)
CARDIOVASCULAR II--reinforce lecture on acetylcholine, epinephrine, stretch effects on heart
--reinforce lecture on microcirculation and its regulation
CARDIOVASCULAR III--reinforce lecture on hemodynamic equation in human rest and activity;
--also know main parts of ECG: P, QRS, T parts; and heart CYCLE events!
RESPIRATION-- part A: know structures, basic functions, how lungs inflated with pressure changes. part B: basic concept/roles of TV and VC; Part C: regulation--how gases/H change under various condition; how the brain regulation responds; RMV=BR x TV; and CIRCULATORY TRANSPORT lab: know how hemoglobin works, and evolutionary /adaptive differences among vertebrates.
FROM LECTURE HANDOUT READING: know especially these
Lecture #22: --my TITIN box on p2: what are its functions?
--ATHLETES EXPLOIT: know basics of diagram!!
--RUN ALL DAY: how did the researchers boost mice marathon ability with WG1516?
Lecture #23: -- CAN GENES PREDICT.. what is ACTN3 and the testing/ETHICAL issue here?
--LURING AWAY MYOSTATIN may help how?
--SCIENTISTS REVEAL..how do Froghopper insects jump so powerfully?
--two HUMAN articles: how have our legs/feet evolved for locomotion?
Lecture #24: --CARDIOVASCULAR DISEASE LINKED..how do mammalian and avian clotting systems differ and why does that make us more susceptible to heart attacks?
--LIGHT PLUSE KEEP..how might optogenetics benefit a person's defective heart pacemaker?
Lecture #25: --THE 43kd POLYPEPTIDE [the main gap jct protein]..know what my mom wrote about gap jcts!
--REPTILE RESEARCH..reveals what about the evolution of a 4-chambered heart?
Lecture #26: --A CHANGE OF HEART..how might one gene have led from 1 to 2-chambered vertebrate heart?
--IF YOUR SYSTOLIC STINKS..what is the role of rotten-egg H2S gas here? Note eating garlic boosts H2S..
Lecture #27: --TIGHT NECKTIE..why don't I ever wear these things?
--FIG 11-2: know this!
--YOUNG APPARENTLY HEALTHY..what is this health concern and its causes?
Lecture #28: DINOSAUR AND ALLIGATOR ARTICLES!! Know basic finding, evolutionary significance
--WHY WIND TURBINES--kill more bats than birds due to respiratory differences?
Lecture #29: --Excerpt from Why We Get Sick--how did 'choking to death' glitch evolve?
--NEW ARTIFICIAL LUNG works how?
--YOUNG BLOOD--scientists used gene regulation how?!!!
Lecture #30: know findings about Spleen and Neuroglobin!