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The Glowing Golden Bible of Physiology.doc

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Human Kinetics
HK 2810

The Glowing Golden Bible of Version 2.0 (2002 version) HK*3940C. Murrant and M Bakovic Table Of Contents Themes: Feedback – p. 3 Functional Segregation – p.6 Time Dependence – p.10 Convergence/Divergence – p.12 Summation – p.14 Local vs. Central Control – p.16 Redundancy – p.19 Importance of Ca - p. 21 Na /K ATPase – p. 22 Autoregulation – p.23 Ohm’s Law – p. 25 Transport – p.26 Acidosis/Alkalosis – p.27 Challenge: Respiratory Acidosis – p. 29 Respiratory Alkalosis – p. 30 Metabolic Acidosis – p.31 Metabolic Alkalosis – p.32 Exercise – p.33 Hypovolemia & shock – p.35 Infusion of Saline – p. 36 Hypoxia (Altitude) – p. 37 Effect of Alcohol – p.38 2 Feedback Communication within any system is essential in order for control and regulation to be efficient. Feedback & feedforward allow this communication to take place. Feedback is a useful mechanism in the body which sends a response to an organ or system to adjust a change and bring that level of change back to normal, in an effort to maintain homeostasis. Examples: 1. Ventilation - Lung has feedback system working through 3 types of neurons. “A” neurons are inspirators which turn on breathing, these stimulate the interneurons “B” which stimulate “C” which in turn inhibit “A”. - Therefore, when increased CO (Br2ath hold) chemoreceptors stimulate “A”Increase ventilation and feedback from “C” maintains oscillation and prevents hyperventilation (+) C--------------< (-) A (+) >-------Chemoreceptors V / \ / \ / \ / \ / \ / \ ^ B (+) >-----Stretch receptors work on “B” 2. Endocrine - Rate of secretion of hormones is controlled through various feedback mechanisms. - Target performs function – when too much function negative feedback to secretory cell and decrease in secretory rate. Eg. Insulin & Glucagon function as feedback systems to maintain normal blood [glucose]. - If increase in blood [glc] secrete insulin to lower [glc] - If decrease in blood [glc] secrete glucagons to raise [glc] 3. GIT (Gastrointestinal Tract) - The control of emptying and filling of compartments is based upon feedback and feedforward mechanisms. Feedback controls rate at which contents enter compartments. Eg. Excite pyloric sphincter and motility of stomach inhibited. Feedforward controls rate contents exit. Eg. Stomach causes stimulation of motility and secretion 3 - In GIT between the stomach and the SI (small intestine). Gastric factors will stimulate propulsive movement of chyme to SI (hormonal: Gastrin). Duodenal factors (SI)-more potent-inhibition of stomach emptying via the pyloric pump. - Duodenal reflexes Intrinsic, enteric nervous system: duodenumstomach. Extrinsic nerves: vagus nerve, duodenumprevertebral gangliainhibitory sympathetic neurons. -------------------------------->Stomach | | Gastrin (+) | V | Pyloric Sphincters ↓ Synapsin PiExocytosis of Insulin 12 2. Glucose response in different organs Divergence - Islet cells, Liver cells and Adipose cells all respond differently to the same signal (glucose) A) Islet cells Glucose enters via GLUT2 transporteractivates GlucokinaseG-6-P Intracellular receptorGlucose and insulin responsive genesPhysiological change. B) Liver Cells Same as islet cell cascade, but Insulin receptor causes a protein kinase cascade which activates/upregulates GK (Glucokinase). It also uses a GLUT2 Transporter. C) Adipose Insulin receptor recruits a GLUT4 transporter to the cell membraneglucose enters the cellHK (Hexokinase)G-6-PIntracellular receptorGlucose and insulin responsive genes. 3. CVS (Cardiovascular system) Convergence - many different factors influence SA node and HR via convergence: -Convergence & summation of the effects of PNS, SNS, Hormones (ADH-VP, AII, ANP) and stretch or lack thereof influence HR via the SA node. -SNS increases HR, PNS decreases HR -AII, ADH-VP increase HR (Vconstrict of vessels) -ANP decreases HR (Vdil of vessels) -Stretch increases HR from increased Venous Return (increase contractility) Divergence - Many different responses to a change in MAP: - increase/decrease fluid flux from tissues - Vasoconstrict/Vasodilate blood vessels - Increase/decrease HR and Contractility (Stroke Volume) 4. Vision Convergence - Integration and convergence at the LGN and SC to form simple, complex and hypercomplex receptive fields (create lines, angles etc in vision). Multiple inputs enter in different layers of these structures and are integrated via receptive fields. 5. Motor Units Divergence - One nerve impulse can effect many muscle cells (myocytes) and can cause as little as 4 or as many as 400 muscle cells to contract simultaneously. Different types of motor units for different activities, but all diverge one signal to many outputs. 13 Summation Throughout the body when certain tasks wish to be done, there are many positive and negative influences affecting the execution of the task. A net result of positive influences results in a positive stimulation, and vice versa. A result in which the positive and negative influences equal means that there is no change in physiological function. 1. Synapses - Transmission of any stimulus from our environment to processing centres depends on the balance between EPSPs (Excitatory Post-Synaptic Potential) and IPSPs (Inhibitory Post-Synaptic Potential). - For AP (Action Potential) to occur; summation of EPSPs must be > IPSP’s and reach the threshold for the cell. - When threshold is achieved, the AP will fire via Local Current. - If summation of EPSPs < IPSPs, the AP will not be transmitted. 2. Pancreas Secretory Cells - Secretory cells subjected to many stimuli at any given time - Secretion is the balance between excitatory and inhibitory stimuli ___________________ Paracrine H | Secretory cell | (Norepi) SNS (-) Endocrine H| | (Ach) PNS (+) (CCK, GnH, |___________________| RmSubstrates (glc, aa, fats) Secretin) 3. GIT Motility - Motility of stomach depends on relative []’s of GI hormones Gastrin increases motility, decreases time to move food out, increases secretion of gastric juices Gastrin competes against CCK, GIP, and secretin which decrease motility and increase time. Therefore, summation determines motility of the stomach. 4. Kidney – Reabsorption of H 2 and associated BV increase is dependent upon the competition of the hormones on the kidney and their effect on the CD & DT. - ANP & Prostaglandins cause a drop in Na+ and H O 2eabsorptiondrop BV. - ADH-VP and ALDO result in increased Na+ and H O reabsorbtionincrease BV. 2 - ANP inhibits ADH-VP. 14 - Thus, the summation of positive and negative inputs determine if there is resorbption of water and Na+ or not. 5. Muscle – Summation of inputs regulated force of muscle by regulating intracellular Ca -Increase Ca2+ due to increase AP frequency - APT-tubulesclose contact with SRSR release of CaVoltage gated Ca channels openincreased cytoplasmic [Ca]CICR (trigger calcium) - Ca2+ binds with Troponin (striated) to remove troponin from the active sites or Calmodulin (smooth) to activate MLCK (Myosin Light Chain Kinase) and proceed to the phosphorylation of the actin or myosin respectively and then contraction. - Positive inputs: increased intracellular Ca2+ - Negative inputs: decreased intracellular Ca2+ (Ca pumps, Ca channels) 6. Vision - Spot of light on one receptive field may send an EPSP to the bipolar cells of the eye, while another receptive field may send an IPSP to the horizontal cells, which when stimulated would send EPSPs to the same bipolar cell. The summation of these inputs determines if the cell is excited or not, and is important in contrast with vision. 7. Endocrinology – Pancreas beta-cellsLevel of activity dependent on: A. GI hormones (Stimulate secretion of insulin, can be anticipatory) B. [glucose]increase stimulates insulin secretion and vice versa C. [AA], [FA]increased also stimulate secretion of insulin D. SNS (beta) and PNS (Ach)Stimulate secretion of insulin E. [glucagons]increased will stimulate insulin secretion F. Somatostatininhibits secretion of insulin G. Insulininhibits itself (autocrine) H. SNS (alpha)inhibits secretion of insulin 15 Local Versus Central Control Brain and Spinal cord (CNS) monitor the interaction of our many bodily systems ensuring our survival overall, however they don’t have the capacity to maintain/monitor everything at all times (too much traffic). Therefore we have local tissue control systems present in a variety of systems which work both independently and in cooperation or competition with the CNS. 1. Pancreatic Beta-cell control A) Central Control: ANSPNSAch (+) = Insulin secretion ANSSNSNE (-) on alpha 2 receptors = downregulation of Insulin secretion ANSSNSNE (+) on beta receptors = Insulin secretion (ANS = Autonomic Nervous System) B) Local Control Hormones produced by pancreas: i) Alpha CellsGlucagon (G) ii) Beta Cells Insulin (I) iii) Delta CellsSomatostatin (SS) iv) F or PP Cells Pancreatic Polypeptide (PP) These can affect the beta cells within the islets before even entering the bloodstream. (-)G(-) ^ ^ / \ / \ / \ / \ V V (+) (+) Autoinhibitory (-)I (-)(+)SS---->(-)PP 2. GIT – Intrinsic and Extrinsic NS A) Central – Extrinsic NS ANSPNSAch (+) excitatory ANSSNSEpi (-) Inhibitory 16 *Extrinsic nerves synapse on ICC cells (Interstitial Cells of Cajal) (not directly on GI smooth muscle) B) Local – Intrinsic (Enteric) NS -ICC cells produce electrical signal in smooth musclespecialized and produce pulsesAutomatic. -Sensors for Mucosa or distension stimulate interneurons to fire, causing the GI enteric hormonal system to be stimulated (Gastrin, Secretin, CCK, GIP, etc).Key in peristalsis. - Cooperation of central and local control. Central will control if necessary, but enteric NS is normally enough to autoregulate and allows CNS to monitor other things more closely. 3. Respiratory System - Local and central control involve pO 2nd pCO val2es. A) Central Control – aortic and carotid bodiesadjust Ventilation Medullary Chemoreceptors B) Local Control – match flow (Q) and Ventilation (V) to increase efficiency Example: Sensors on pulmonary vein side pick up low O in 2he bloodVconstrict pulm arterydecrease volume in pulmonary capillarydecrease QIncrease equilibration timemore O sat2rationincreased O . 2 4. Kidney regulation of BV A) Central Control – hormonal regulation by ADH-VP, ALDO, ANP - all induced by centralized sensors (baroreceptors) stimulating renal resorption - Central AII will increase ADH-VP secretion and ALDO secretion - ANP is generally an inhibitor (on ADH-VP, Renin, AII, ALDO) - Working to increase BV. B) Local Control – Tubuloglomerular feedback mechanisms increase GFR to try to Increase Q in tubule to maintain osmolarity in macula densa. Example: If Increased BV (increased MAP etc) Centrally: Increased stretch of Right AtriaANP(inhibits) AII, ALDO, ADH-VPVdilate aff and Vconstrict effIncrease of P IncreGse of GFR 17 Increase of Q in tubuleH O2loss (as well as increase in osmolarity as the fluid spends less time by the Na+K+Cl- Symporter) Locally: Increased MAPIncreased P IncGeased Q in tubuleIncrease osmolarity in Macula DensaVconstrict affDrop P DropGGFRDrop Q in tubuleOsmolarity back to normal. Hence, local is working against Central control to maintain a relatively stable osmolarity while regulating blood volume. 5. Reproductive Systems - Hromones play a very big role in the regulation of reproductive systems in both men and women, locally and centrally. A) Central - Anterior pituitary secretes LH and FSH which act on leydig and sertoli cells in men, or theca and granulosa cells in women. - In women, these hormones will control development of dominant follicle and ovulation. B) Locally -Estrogen (secreted from ovary) increases the number of Rm for FSH and LH which maintains [FSH] and [LH] - Testosterone secreted by leydig cells will stimulate Sertoli cells to stimulate spermatogenesis, as well as releasing testosterone systemically. - Sertoli cells act as the blood-testis barrier and guide the developing spermatids through their development, and release them at the appropriate times into the lumen. - The corpus luteum in females will secrete Progesterone to thicken the uterine wall in preparation of implantation. - Theca cells produce male-hormones (androstenedione, testosteronestimulated by LH) while Granulosa cells use aromatase to change these to Estrone and Estradiol respectively (stimulated by FSH). 18 Redundancy During execution of a physiological task usually there is an abundance of different activators or inhibitors. This abundance acts as a backup in case one or more fail. 1. CVS - The ability to change radius of blood vessels involves many factors: Neural SNS: release ACHVD (increase radius) release NEVC (decrease radius) Hormonal: Beta-EpiVD or i
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