07-PHYSIOLOGY

viscosity measure-Osborn viscometer pulse-Dudgeon sphygmograph Surf Tension-STalagmometer orexin-wakefulness, appetite, Alz ds ACh secret eye-Amacrine cell

ANS↑ M1-stom( HCl)

↓ ↓ M2-AV>SA node( conduct vel, ventricle rate)↑ ↑ M3-sm m(EDRF-vasodil), bronchospasm, GIT( motility), freq micturition, salivary,

lacrimal, sweat gld, constrictor pupillae, ciliary m

CELLcell memb fluid mosaic/Singer Nicolson model lipid wt:prot wt=1:1 SA-carb:lipid:prot=3%:42%:55%

↑ ↑ lipid bilayer-self sealing, hydrophobic-MI-phospholipid, FA- fluidity cholesterol-fluidity buffer

→↓ temp>Tm fluidity→↑ temp<Tm fluidity

highest prot-inner mitoch memb(70%) highest lipid-Schwann cell memb ubiquitin-tags prot for removal in 26S proteosome

phosphatidylserINe(marker for apopt)-flipflop movem, on INner layer, comes on outer layer FA&cholesterol-on both leaflet(outer&inner) all glycOlipid-on Outer surf, CHO–chain projecting Outside RAFT-region within memb with high metab activity, rich in cholesterol& GPI anchored prot-caveolin

↑ ↑ lecithin bel pKa- surf potential> dipole movem

prot extracell-Ig transmemb(integral)-glycophorin, IgG superfamily periph(on inner layer)-spectrin, ankyrin

Aim4a

iims.i

n

intracell-Hb

filament micro-weakest, endo,exocytosis-actin intermed-join microtubule& microfilament- laminin, keratin, vimentin, desmin, GFAP, peripherin, neurofilament microTubule-sTrongest, mitotic spindle, separation of genetic material-tubulin

molecular prot ATPase

→ kinesin-axoplasm trpt +ve end microtubule dynein

→ cytosolic-move vesicle –end of microtubule axonemal-power ciliary& flagellar prot

myosin-m contract GTPase dynamin-endocytosis

jnal region b/n 2cell desmoSome/macula adherenS-tensile Strength in Skin, gum, cx gap jn/connexon(hemich=6connexin)-bidirect free passage of material b/n 2electrically coupled cell, 3μ, no synapt delay-heart tight jn prot/zonula occludens occludens claudins Jn Adhesion Molecule(JAM) BBB,stom wall,UB wall

focal adhesion molecule-generate intracellular signal when subject to stress

gap jn prot connexins(6subunit)cell adhesion molec(CAM) Cadherin(Ca depend cell adhesion molecule) integrin-leucocyte adhes to endoth cell selectin-leucocyte rolling IgG superfamily-ICAM,PECAM

tpt prot pore(aquaporin,perforin)-always open ch-intermittent open voltag gated-Na ch in n memb(blocked by tetrodoxin, saxidoxin) ligAnd gated-ionotropic recept, GABA-A(Cl), nAChR-fast

Aim4a

iims.i

n

metaBotropic recept-cNG gated, GABA-B, mAChR, cGMP gated(rods) time gated-slow Ca ch(Purkinje fibre) mech gated-touch recept(skin)

carrier facilitated diffusion

sec active tpt-GLUT,SGLT pump P-ATPase, E1-E2 ATPase, Na-K ATPase, SERCA V-ATPase H+ trpt F-ATPase

study of ch patch clamp technique

best –ve feedback mech-temp regulat> osmoregulat

urea tpt UTA1,2,3,4-kidn UTAB-RBC

→ → prot synth in ribosome on RER initial folding of polypeptide chain in RER cis end → →of Golgi app storage, conc, process, packaging, sorting in Golgi app trans end

→ → →Golgi app secret vesicle in cytosol cell memb exocytosis

exocytosis/cell vomiting/reverse pinocytosis/emeiocytosis constitutive-continuous(mucus secretion, IgA secretion) Ca ATP docking prot syntaxin(key snare prot) synaptobrevin μ snare prot SNAP-25

endocytosis constitutive-continuous, no sp signal req(vit uptake) Ca ATP clathrin(LDL uptake, ion uptake in GI cell) caveolin(endoth cell for absorption of nutrition,FA) dynamin/pinchase ligand-recept complex in pinocytosis dissociate in endosome d/t acidic pH of vesiclevesicular tpt(cytopempsis)

Aim4a

iims.i

n

permeability across cell memb H2O> indole> glycerol= urea> Try> glu> Cl> K> Na

total body H2O(60%) ICF(40%) ECF(20%) interstitial fluid(15%) plasma(5%) spaces-pleural,pericardium(1.5%)

compartment-indicator TBW-D2O>tritium oxide, antipyrine, aminopyrine ECF-inulin(most accurate), sucrose, mannitol, Na thioSO4, Na22, I125 iothalmate plaSma vol-EvanS blue(T1824), sr albumin label with I125 bld cell vol-Cr51 label RBC interstitial fl vol=ECF–pl vol ICF=TBW–ECF bioimpedance spectroscopy RBF-PAH GFR-most accurate(inulin), MC(creatinine)

Na-K pump fn-cell vol regulat>RMP heterodimer α(larger) ECF side-K bind site, ouabain(digitalis) binding site

ICF side-Na binding site, ATP binding site, phosphorylat site(Asp376)↑ T3,T4- no.

↑ aldosterone- no.,activity↑ insulin- activity

↓ ANF,dopamine- activity

hypokalemia hyperpolarisation

hyperkalemia↓ depolarization, excitat

heart stop in diastole

hypercalcemia Ca-memb stabilising heart stop in systole

Aim4a

iims.i

n

hypocalcemia↑ excitability

Cl ch(anim,bact)-dimerepith Na ch-trimerK ch,aquaporin-tetramerCl ch(human),lig gate ACh ch-pentamer

RBC memb at rest most permeable-Cl RBC RMP(–10mV) d/t-Na K pump neuron RMP(–70mV) d/t-K neuron RMP close to-K neuron RMP equal to-Cl

organ max hydrostatic press-kidn(46mmHg)organ with max Kf(ultrafiltration constant)-Kidnmax permeable capillary-liver

CVScardiac m(striated,involunt)

↑ intercalated disc-Zline- cell adhesion, provide electromech tethering gap jn-fnal syncytium sarcotubular system-Zline voltage sensor-dihydropyridine Ca source-ECF(maj)+ sarcopl reticulum

↓ unphosphorylated phospholamban- SERCA 1T tubule/sarcomere along Z line elasticity-titin myosin heavy light chain α,β-fetal heart α-adult atrium β-adult ventr

internodal path(AMP-BWT) Ant-Bachman Mid-Wenkebach Post-Thorelbundle of His-gives lt br, continues as rt brgate cell merge with-Purkinje fibre

ventr AP RMP=–90mV 0-depolarisat-Na influx

Aim4a

iims.i

n

1-early repolarisat-K efflux 2-plateau-Ca influx 3-late repolarisat-K efflux 4-hyperpolarisat-delayed closure K ch

SAnode AP RMP=–60mV

↓ 0-depolarisat- K efflux, opening funny ch(Na>K), Ca influx(Ca ch-main) 3-repolarisat-K efflux 4-prepotential phase-delay closure K ch

↑ → ↑ → → ↓ → ↑ sympath- Gprot cAMP phosphorylat prot depolar time HR↓ →↑ →↓ → ↓ parasympath-( cAMP depolar time), (open KACh ch in ph4 slope of ph4) HR

→ ↓ → ↓ CNX slope of prepotent(pacemaker potential) HR

→Purkinje fibre-prepotent AP

Depolarisat heart(DAN)→ → → → 1st-SA AV atria ventr(1st-lt upper part intervent septum rt), Apex,

eNdocardium→ last-base epicardium

repolarisat→ ventr(1st-base,epicard last-apex,endocard)

part-conduction speed(m/s) SA node=0.05 AV node=0.05 bundle His=1 Purkinje fibre=4

part-impulse(gen/s) SA node=80-100 AV node=40-60 Purkinje fibre=15-40

↑ +cHRonotropic- HR↑ +Dromotropic- conDuction

↑ +inoTRopic- conTRactility↑ +bathmotropic- excitability

→ adenosine affer arteriole constrict(A1), coronary vasodilatat

vasomotor centre

Aim4a

iims.i

n

nucleus tractus solitarius cauDalVLM(meD)-Depressor rostralVLM(lat)-pressor

↓ ↑ stimul-cortex, limbic syst, pain, chemorecept, pO2, pCO2, MAP<60mmHg↓ nucleus ambiguus(parasympath)- HR

carotid sinus→↑ ↑ b/l transect HR, BP

→↓ ↓ b/l clamping above carotid bifurcat HR(1st), BP

exerc does not reduce bld supply-brain max bld flow/min-liver max bld flow/min/100g-kidn max O2 consump/min-liver max O2 consump/min/100g-heart max AV diff at rest-heart min AV diff at rest-kidn

Fahraeus-Lindquist effect↓ →↓ diam<2mm- diam viscosity↓ →↑ diam>2mm- diam viscosity

most potent vasoconstrict-endothelinmost pot circulat vasoconstr-urotensinmost potent vasodilat-NO

↑ ↑heamatocrit in venous bld - Cl

capacitance vess-less elastic ts& sm m

ENDOCRINE amine-T3,4, NE,epinephrine, dopamine steroid-cortisol,mineralocorticoid, vitD3, testosterone,E,P peptide-other shortest peptide h-TRH longest peptide h-hCG shortest t½-catecholamine(few s) longest t½-vitD(15D) shortest latency of act-oxytocin(few s) longest latency of act-thyroxin(48h)

↓ T3-starvation, postoperative, c/c illness, a/c illness↓ T4-c/c illness, liver dysfn

Aim4a

iims.i

n

↓ TSH-postoperative, a/c illness↓ Wolf Chaikoff effect- organic bind of I2

thyroxin binding prot freeT3=0.2%, freeT4=0.02% thy bindin globulin(maj thy h bind prot) thyroxin binding albumin thyrox bindin prealbumin(transthyretin)

paracrine regulat factor release by 1cell act on adjac cell

↓ pancreat somatostain- insulin secret

autocrine regulat factor release by a cell act on same IGF1-chondrocyt,breast epit,gonad cell

↓ANP- HR,BPsec messenger for GnRH-phospholipaseC

hormesis dose response phenom

↑ ↓ low dose- , high dose- J/invert U shape effect of chemotactic peptide on neutrophil adhesion

proopiomelanocortin(285AA) ACTH,MSH βlipoprot h γlipoprot h βendorphin CLIP(CorticotropLike Intermlobe Peptide)

P metab↓ NaPiIIa-absorpt in PCT- by PTH

NaPiIIb-absorpt in duod,SI NaPiIIc-absorpt in PCT

GH-early division spermatogenesis↑ -exercise, fasting, stress↓ -REM sleep

↑ →age↓ h-aldosterone, calcitonin, GH, prolactin, renin, E

Aim4a

iims.i

n

↑ h-PTH, FSH, LH, NE —h-cortisol, epinephrine, insulin, T3,T4, testosterone, GLP1)

PTH(84AA polypeptide)↓ →↑ sr Ca++ sr PTH

action↑ -Ca resorp fr bone, Ca reabsorp fr DCT

→ → → → → → liver angiotensinogen(α2globulin) (JGcell renin) angiotensin I (ACE) → → → →angiotensin II (aminopeptidase) angiotensin III (angiotensinase) active

fragm

→ → ↑ → ↑ aldosterone cytoplasm recept transcription of mRNA in ren tubule synth of Aldosterone Induced Prot(ATP)/NaK ATPase& βsubunit of amiloride sensitive Na ch

mineralocorticoid recept-DCT, cortical CD, sal gld, colon, brain(hippocamp), myocard, periph vasc resist, brown adipose ts, sweat gld↑ ↑ - hyperkalemia> angiotensin II> ACTH> hyponatremia

vassopressin recept(GPCR) V1/1A-Ca,IP3-glycogenolysis(liver), vasoconstrict, PLT aggregat, intest contraction

↑ ↑ V2-cAMP- H2O reabs fr CD, release factorVIII& vWF↑ V3/1B-Ca,IP3- ACTH

erythropoietin synth-peritubular capillary(juxtatubular interstitial cell) in renal cortex(85%)+ perivenular hepatocyte liver(15%)

insulin secret↑ ↑ - glucagon, pl glu↓ ↑ - sympath stim, somatostatin, salicylate

GITtaste

↑ bitter-GPCR, intracell Ca(IP3DAG) salty-amiloride sensit Na ch

↑ → sour- intracell H+ close K ch↑ → sweet-GPCR, cAMP close K ch

umami-Glu recept(MSG, diNaGMP, diNaI MP)

electrical activity of sm m RMP=–50-–60mV

Aim4a

iims.i

n

basic electric rhyth-d/t oscillat in activity of Na-K pump(variable freq)=5-15mV max freq-duod(12/min), min freq-caecum(2/min)

enteric NS intrinsic MYenteric/Auerbach plex-Motility SubmucoS/MeiSSner plex-Secret, bld Supply

extrinsic parasymp sympath

→ Migrating MOTor compLex(MOTiLin)-fasting, ring of contract-body of stom dist ileum, fn-clearing action, occur>2h after last meal, cycle=5cm/min×90min massive active contraction-colon during defecation max postprand motility-sigmoid colon> descend colon> transv colon pacemaker cell of GIT-interstitial cell of Cajal-midportion of stom pacemaker potential SI-duod Revers peristalsis-Rectumsegmentation/mixing contraction promote progressive mixing of food particle duod<12/min term ileum=8-9/minstimulus for receptive relaxation of stom-entry of food

GI hstom chief/zymogen/peptic-pepsinogen G(pyloric antrum)-Gastrin D1/oxyntic/parietal-ghrelin, HCl, intrinsic factor of Castle D-somatostatin ECL-histamineSI I-CCK S-Secretin K-GZP L-GLP1 M-Motilin δ-somatostatinpancr α-glucagon β-insulin,amylin,C peptide δ-somatostatin E-ghrelin F-pancr polypeptide

Aim4a

iims.i

n

gastrin↑ HCl,delay gastric emptying

CCK↑ ↑ CCK- prod of prot digest

↑ ↓ GB contract, pancr enz secret, secretin action, satiety, NTsecretin↑ HCO3 in bile& pancr juice GIP(Glu dep Insulinotropic Peptide)↑ insulin

ghrelin↑ ghrelin-sleep deprive, anorexia

↑ ↑ ↑ orexigenic, fat deposition, choice of food, memory, GH

salivary secretion HCO3, amylase, lingolipase(Ebner gld on tongue dome), lysozyme, kallikriene, K(max amount) phase-cephalic(MI), oral, gastric

gastric secretion→ → pepsin, G-lipase, HCl(MI)(bactericidal, pepsinogen pepsin, Fe+++ Fe++)

phase-cephalic,gastric,intest

intest secretion Paneth/ZYMOgEn-lysOZYME N-Neurotensin L-gLucagon

→ disaccharidase, di&tripeptidase, enterokinase(trypsinogen trypsin)

colon secretion K(max conc)

bile salt amphipathic nature

→ emulsificat fat in SI detergent actionbile uptake by hepatocyte-Na dep

absorption stom-weak acid, weak base, salicylate,alcohol duod-Fe++(max), Ca, Na, Cl, vit, FA, AA, SO4, sugar jejunum-carb, prot, fat(long chain), alcoh(max), FA(max), Na(max), H2O(max-5500ml), Ca(max), vitB9(max), Ab dist ileum-90%bile salt(max), vitB12(max) colon-5%bile salt, electrolyte, H2O(1000ml), short chain FA(by colonic bact)

Aim4a

iims.i

n

Fe(prox duod)→ → → → food(ferric Fe+++) absorb(ferrous Fe++) tpt(Fe+++) store(Fe++) <1mg in

stool heme Fe absorpt=65%

↑ hepcidin(Fe metab regulat h)-produce by liver, in anem of c/c ds-–ve regulator of absorpt-lysosomal destruct of ferroportin, a/c phase reactant

fru absorpt GIT-facilitat diffusion

orexigenic agouti related peptide(AGRP) melanin concentr h(MCH) neuropeptide Y orexin A,B endorphin galanin AA-Glu,GABA cortisol ghrelin GHRHanorexigenic(CCALSIBhiGiliNahi) CRH Cocaine Amphetamine Regulat Transcript(CART) Alp Melanocyte Stim H(αMSH) Leptin Serotonin Insulin Bombesin GLP NE

high glycemic index-corn flakes

sirtuin(SIRT) metab(NAD dep deacetylase 5) 1-intranucl 2-cytoplasm 3,4,5-mitochondria 6-heterochromatin assoc nucl 7-nucleolar

LES tone

Aim4a

iims.i

n

↑ -ACh,neostigmine,SCh,morphine↓ -NO,VIP,atropine

GI peristalsis↑ -ACh,subsP↓ -VIP,NO,ATP

KIDNEY↑ ↓ Angiotens II act on Eff arteriole, (low conc)- GFR, (high conc)- GFR

↓ Epinephrine-act on Aff arteriole, GFR(A attack E, E attack A)

renal handling of diff subst not filt-prot freely filt, not reabs, not secret-inulin freely filt, compl reabs-glu, AA, HCO3(MI buffer, 24mEq/l) freely filt, partl reabs-electrol, urea(52%), H2O(99.5%) freely filt, compl secret-PAH(low conc) freely filt, partl secr-PAH(high con), creat

glomerulotubul balance, max H+ secret by-PCT acidification urine-CD 1st part kidn affect in hypoxia-medulla GFR max-3rd decade pacemaker ureter-minor calyces DCT secrete-NH3

collecting duct P(Principal) cell-Na reabsorpt, ADH stimulat H2O reabsorpt I(Intercalated) cell-H+ secret, HCO3– tpt

Ca 99% reabsorb=65%PCT+ 25-30%thick ascend limb Henle loop+ 4-9%DCT,CD

free H2O clearance urine is hyPOtonic with plasm-POsitive urin hypertonic with pl-–ve isotonic=0

aquaporin 1-basolat&apical memb PCT, thin desc limb loop Henle 2-lumin memb CD 3-basolat memb CD

Aim4a

iims.i

n

4-basolat memb CD,brain 5-sal,lacrim,resp 9-WBC,liver,lung,spleen

JG apparatus(cortic nephr) JG cell-tunica med of affer arteriole, secrete renin macula denSa/modif tubular epith cell, beginning of DCT, Sensor for Na&Cl Lacis/extraglom mesangial cell-take up immune complex in GNephritis

countercurrent mech muLtipLier-Loop HenLe(create interstit hyperosmolarity-max=1200mosmol/l), driven by conc of Na exChange-vasa reCta(maintain medullary hyperosmol)

glu abs in kidn prox PCT-SGLT2,GLUT2 distal PCT-SGLT1,GLUT1

GLUT1-constitutively expressGLUT2-glu exitGLUT3-neuronGLUT4-insulin dep,m,adipose tsGLUT5-fruSGLT1-GIT(1Na:2glu)SGLT2-kidn(1Na:1glu)SGLT3-kidn(1Na:1glu)

NS BBB d/t-tight jn b/n endoth cell> astrocyte CNS-1oligodendrocyte:20axon PNS-1Schwann cell-b/n 2node Ranvier

AP in spinal motor neuron arise in-init seg(high Na ch per unit area)> axon hillock AP in sens neuron arise in-init node of Ranvier(max Na ch per unit area)

AP cathode ray oscilloscope-patch clamp techn RMP=–70mV firing level=–55mV depolar-Na influx overshoot=+30mV(close to equilibrium potential Na)

↓ ↑ repolar- Na permeability, delay K permeab(K efflux)↓ afterdepolar-slight K effux rate

Aim4a

iims.i

n

hyperpolar=–71-–72mV cell with K efflux depolar-haircell cochlea cell with Ca efflux depol-heart(SA node) Na-2gate(M-activat, H-deactivat), 3possible state K-1gate(M) demyelinat upto 3node Ranvier-stop AP propagation in n

refractory period→ ⅓ absolute-depolarisat repolarisat

⅓ → relative- repolarisat start of afterdepolarisation

fastest velocity n-low Ra(resist), high Rm(memb resist), low Cap node Ranvier-low Rm, high cap

→ rheobase-min strength current response→ utilisation time-time taken by rheobase response

→ chronaxie=time 2×rheobase response

lesser chronaxie-more excitable ts n<sk m<card m<sm m n Aα<Aβ<Aγ<Aδ<B<C

multiple sclerosis→↓ demyelinat space constant

classif of n fibreERLANGER&GASSER(sens,mot,aut)A(myelin) α(I)-somatic motor, sens propriocept β(II)-sens propriocept(m spindle), vibrat, deep press, touch γ-motor to m spindle δ(III)-fast pain(glut), temp, cold B(myelin)-preganglionic autonomicC(unmyel)(IV)-sens, autonomic, slow pain(subP), cold+warm, crude touch, press, postgang sympath

LLOYD&HUNTS NUMERICAL IΑ(Aα)-sens(m spindle) IB(Αα)-sens(golgi tendon organ) II(Αβ)-deep press III(Αδ)-mot to m spind

Aim4a

iims.i

n

IV(C)-slow pain, touch, press

myelinated-conduct vel=6×diam unmyelinated-CV=√diam fastest conduct-propriocept

suscept to(PHir Laya ABC BABa) Press-A>B>C Hypox-B>A>C Local anaes-C>B>A order of block-aut> sens[temp(cold> hot)> pain> touch> press> propriocept)> motor] order of recovery-motor> sens> autonomic

reflex asynaptic axon reflex

→ blunt inj(Lewis triple response) red rxn (hist)+ FLare(axon reFLex)+ wheal(hist+ bradykinin) monosynaptic DTR

↑ stimul- m LEngth recept-m spindLE affer-IA,II centre-spinal cord effer-Aα response-m contract, maintain m tone no. of synapse=1

bisynaptic inverse sTrEtch reflex

↑ stimul- m TENsion recept-Golgi TENd org(1GTO/13-15m fibre) affer-Iβ centre-spinal cord effer-Aα response-m relaxat no. of synapse=2

m spindle intrafusal m fibre(Aγ) nuclear bag(1-3) dyNamic-aNNular spiral ending(IA)

Static-flower Spray ending(IA,II) nuclear chain(4-5)

Aim4a

iims.i

n

static(IA,II) extrafusal fibre(Aα-contraction)

axonotmesis-motor march

degeneration& regeneration of n Wallerian degeneration(CAM)-change in distal stump+ prox stump upto 1node of R 24-48h-Chromatolysis(n cell body swell, Nissle granule disapp) upto3d-distal stump carries AP 3-6d-Axonal degenerat distal stump 6-10d-Myelin degenerat 10d-oil droplet in empty tube 15d-repair start-sprouting fr prox tube, Schwann cell proliferat 80d-repair completed(80% diam)

axoplasmic tpt Ca ATP microtubule(α&βtubulin) molecular motor-kinesin, dyenin, myo V fast(kinesin)

→ Antegrade(400mm/d) Assembl(+) end→ retrograde(200mm/d) disassembl(–) end-rabies virus(3mm/h), TT, nGF

slow(dyenin-antegrade) 0.5-10mm/d

microfilament

neurofilament-maintain diam of axon

receptor-sensation Rapidly adapting(RMP) Meissner corpuscle-fine touch, low freq vibration(80Hz)

PaciniaN corpuscle-vibratioN Slowly adapting(SMR) Merkel disc-crude touch, pressure, texture, fine touch Ruffini end organ-crude touch, sustain pressure, jt position

other free n ending-touch, pain, pressure hair end organ-movem of object on body Krause end bulb-cold

thermal receptor Aδ&C-cold, C-warmth

Aim4a

iims.i

n

10°C—24°C(max activat)—40°C overlap-30-40°C

response to cold→ ↑ → environm temp<23.8°C sympath system periph vasoconstriction

↑ → non shivering thermogenesis- β3 uncoupling of oxidative → ↑phosphorylation(UCP1=10-15%) heat

shivering

heat loss at ambient temp(21°C)-radiation

receptor for mod cold-CMR1

neurotrophin-recept nGF-TrkA BDGF(Brain Derived GF), NT4,5-TrkB NT3-TrkC

trp(transient receptor potential) ch family of excitat ch vanilloid recept-TRPV1,4-noxious heat, Chem(Capsaicin), pain acid sensing ion ch-H+ Purinergic recept-P2X,P2Y-Pain ankyrin recept-cold menthol recept-mod cold

neurotransmitter small molecule, rapidly acting ACh amine epinephrine NE(locus cErulEus) D(substantia nigra) hist 5HT(raphe magnus)

Gly(inh), GABA(A-open Cl ch,B-close K ch), Glu, Asp gas-NO large molecule, slowly adapting neuropeptide hypothalamic peptide(GnRH,TRH) pituitary peptide(ACTH,TSH) gut-CCK

class

Aim4a

iims.i

n

I-ACh II-amine-hist, epinephrine, D, NE, 5HT III-AA-Glu, GABA, Gly IV-small molecule-NO, adenosine

transmission in sympath ganglia fast EPSP-ACh(ms) slow EPSP-AChM1(s) slow IPSP-AChM2(s) late slow EPSP-GnRH(min)

sweat gld secret-sweat+VIP

NM ds presynaptic-tetanospasmin, botulinum toxin, Lambert Eaton synd postsynaptic-myasth gravis, strychnine

decortication damage to corticoretic tract-mod rigiditydecerebration damage to corticoretic& basal ganglia tract-severe rigidity

sk m(striate,voluntary) contractile prot AcTin(polymer of f-actin, 2strand in double helix, ATPase activit)

myosin II regulating prot tropomyosin(1molecule cover 1active site on actin) troponin(I-actIn, T-Tropomyosin, C-Ca)

struct prot actinin(bind actin to Z-line) titin(largest prot, 3million Dalton, attach Z-line to M-line, elasticity to m) desmin(attach Z-line to plasma memb)

sarcolemmal prot→ laminin(EC matrix, attach αdystroglycan)

→ αdystroglycan(connect laminin βdystroglycan) Bet dystroglycan(within memB)

→ syntropin(attach βdystroglycan on inner side memb)→ dystrophin-(connect syntropin actin) Duchenne(absent)-Becker(less) m dystrophy

sarcoglycan(outer side cell memb)-limb girdle dystrophy perlecan(EC matrix, endoth cell) sarcospan(within memb)

Aim4a

iims.i

n

2T tubule/sarcomere(at jn of I&A band) DHPR(T tubule), RYR(L tubule) 1thick filam surround by-6thin filam 1thin filam surround by-3thick filam thin:thick=2:1 1thick filam=500myosin molecule 1thin filam=7actin+3troponin+1tropomyosin Sarcomere-Struct unit m motor unit-fnal unit m sarcotubular syst-AI jn voltage sensor-voltage gated Ca ch Ca source-sarcopl reticulum

H(Hexagon) zone-only myosin pseudoH zone-reversal of polarity of myosin head(no myosin head) A(Anisotropic,dArk) band-myosin+over lapping actin I(Isotropic,lIght) band-actIn Z line-b/n 2sarcomere, centre of I band M(Myomesin) line-centre of A band sarcomere=½I+A+½I during contract↓ I-↓ H-

A-no change Z lines-come closer M line-more prominent CM(Contraction M) band-at 1.5μ CZ(Contract Z) band-at 1.25μ

walk along theory-1ATP-1cycle

Huxley sliding filament/Rachet/walk along theory→ → → cross bridge power stroke ATP hydrolysis recocking

type1 m(SOR1) Small,Slow Oxidative metab Red longer twitch more mitoch more Mb slow sustain contract delay fatiguability standing-ATP store=7-8s

Aim4a

iims.i

n

type2a m mod oxidat metab mod glycolysis walkingtype2b m fast fatiguable running energy supply 100m-85% glycolysis 2mile-20% glycolysis marathon-5% glycolysis

at optimum lth sarcomere-max overlap b/n actin&myosin, max no.actin-myosin cross bridge, max tension

slow twitch motor unit recruit 1st,100-500m fibre, innervat by αmotor neuronfast motor unit 1000-2000m fibre, αmotor neuron

sm m(unstriate, involuntary) prot-actin, myosin, tropomyosin(relation prot), calmodulin(Ca binding prot), no troponin sinGle unit(Gap jn+)-GIT multiunit(gap jn–)-iris, ciliary bodycontract of sm m

→ → ↑ → Ca influx Ca calmodulin complex myosin light chain kinase phosphorylation → ↑ →myosin head myosin ATPase actin-myosin cross bridge format(latch mech)

relaxat phosphatase/dephosphorylase enzyme thin:thick=15:1 no Z line,dense bodies

ascend tract post column(fine touch, vibrat, conscious propriocept, 2pt discriminat, localisat, stereognosis, ability to judge ° of press) fasciculus Cuneatus(tract of BurdaCh)-UL fasciculus Gracilis(tract of Gall)-LL

→ 1st order-DRG(recept i/l medulla)→ 2nd order-i/l medulla c/l thalamus(VPL)→ 3rd order-c/l thalamus c/l postcentral gyrus(BA-3,2,1)

sensory homunculus(grotesque figure of Penfield& Rasmussen)-max-lip, min-genitalia ant spinothalamic tract(crude touch, itch, tickle, sexual, detection of press)

Aim4a

iims.i

n

lat spinothalamic(pain, temp)→ 1st order-DRG(recep i/l dorsal horn)→ 2nd order-i/l dors horn c/l thal(VPL)

→ 3rd order-c/l thalam c/l cortex spinocerebellar(unconscious proprioception) dorsal(uncross)

ventral(cross) internal arcuate fibre medulla-internal arcuate fibre

Fast pain sharp/prick/stab, epicritic, good, Aδ fibre, mech/therm stimulus, NT-Glu, lat spinothalamic tract(lamina Five substantia gelatinosa)slow pain dull/diffuse/aching/burning, protopathic, bad, autonomic sympath, C fibre, ischem, NT-substance P, tract goes to reticular formation(sleep wake cycle), periaqueduct grey, periventr hypothal(ANS) terminate in thalamus(lamina II of substantia gelatinosa of Rolando)

endogen pain inh endogenous opioid(enkephalin, endorphin)-at site of stimulus, dorsal horn, rostral site gate control theory of Melzac& Wall-large diam Aβ inh C fibre descend pain inh pathw-periaqueduct grey, raphe magnus(5HT), enkephalin

thalamus sens relay nuclei non-specific midline intralaminar

→ ant thal nuclei-Papez circuit-emotion, learning, short long term memory conversion specific VPL-somatic sensation VPM-taste LGB-visual sens MGB-audit sens ventroant, ventrolat-proc msg fr basal ganglia& cerebellum

Papez circuit→ → med temp lobe/hippocampus mammillary body of hypothalamus

→ → →(mammilothalamic tr) ant thalam nucl basal forebrain (amygdala/limbic syst-window ),(neocortex-stored)

Aim4a

iims.i

n

descending tract med,axial m,tone&posture ant corticospinal tectospinal vestibulospinal reticulospinal ponS(Stim)

medulla(inh) lat,dist m,fine skill movem lat corticospinal(pyramidal) rubrospinal/alternat pathw

hypothalamus(TRβ2 recept) response to cOld-pOst response to heAt-Ant osmoreceptor-ant hunger-lat

↑ thirst( 10mosmol/l)-lat(preoptic nucl) rage-lat satiety-ventromed(cocaine amphet regulated transcript) reward-med forebrain bundle, nucleus accumbens(drug addict-D3), ventromed self stimul-med forebrain bundle agGREssive resp-periaqueductal GREy Punishment-Periaqueductal grey Circadian rhythm-supraChiasmatic sleep-preoptic sexual-Antmost(mAl)& postmost(fem) portion

brain area involving self stimulation ventral tegmentum med forebrain bundle nucleus accumbens(D3) frontal cortex

cerebellum(3part, 4nuclei, 5cell)→ lat med-DEGF

neo/cerebrocerebellum-Dentate nucleus(largest), motor planning palaeo/spinocerebellum-Emboliform(dist m)& Globosus nucl archae/vestibulocerebellum-Fastigius nucl(oldest), floculonodular lobe-postural balancecell(GBSPG) Granular(E) basket(I)

Aim4a

iims.i

n

stellate(I) purkinje(I) golgi(I) afferent fibre

→ → inf oLIvary nucl (cLImbing fibre) +Purkinje cell→ → → → other affer input (Mossy fibre) +granular cell (parallel fibre) Purkinje cell

greatest populat of neuron-cerebellum silent area of brain-cerebellum(does not show evoke potential) fnal unit-Purkinje cell, deep nuclei vermis-maintain stand& walking posture feed forward inh-basket, Purkinje cell

connection/tract of cerebellum(RO DEV MainCabSeThaVaha IC SauDinRaha)afferent(cerebell peduncl) inf-Reticulocerebellar, Olivocerebellar, Dorsal spinocerebellar, Ext arcuate fibr, Vestibulocerebellar Middl-Cerebropontocerebellar Sup-Tectocerebellar, Ventr spinocerebellarEfferent(cerebell peduncle) Inf-Cerebellovestibular Sup-Dentatorubrothalamocortical, Reticulospinal

Brodman area-fn 3,1,2(somat sensor, postcentral gyrus)-gen conscious, touch, pain, temp 4(prim motor)-initiat of movem 6,8(premotor)-fineness movem, volunt eye movem 7(visuosensory, postcalcarine sulcus, occipit lobe)-visual sense percept-homonymous hemianopia+ macular sparing 9,10,11,12(prefrontal)-intelligence, memory, ego, self respect, social behav, personality 18,19(visuopsychic, parastriate, occipit lobe)-correlation of visual impulse with past memory 22(Wernicke-sup temp gyrus)-audit agnosia/word deaf 41,42(prim auditary-lt temp lobe)-process semantic in speech& vision 44,45(Brocca-inf frontal gyrus)

brain fibre-connection association-different cortic area in same hemisphere commissural-correspond area in 2cerebral hemisphere projection-cerebral cortex with lower level

basal ganglia(CPPG)1)Caudate nucleus

Aim4a

iims.i

n

2)Putamen3)Globus pallidus/pallidum

internum externum

4)substantia nigra pars compacta pars reticulata

5)subthalamic nucl/body of Luy(excitat, glutamate) striatum=1+2 lentiform nucleus=2+3

amygdala nucleus-med temp lobe

nucleus tractus solitarius(medulla) NT-Glu, ACh, GABA, opioid GVA

→ tonsil, pharynx, post tongue, carotid body& sinus CNIX→ pharynx, larynx, trach, esoph, thorac&abd viscera CNX

SVA⅔ → ant tongue CNVII⅓ → post tongue CNIX

→ postmost tongue, epiglottis CNX

integrat centre-postural reflex spinal cord-m tone,+ve supporting rxn, crossed extensor reflex medulla-tonic labyrinthine reflex, tonic neck reflex midbrain-righting reflex cerebral cortex-hopping& placing rxn, long loop stretch reflex

Little Albert study-conditional stimulus to produce conditional reflex

↑nGF- ANS neuron growth

BBB substance cross-H2O, CO2, O2, lipid soluble subst, free steroid h, glu(GLUT1) cant cross-prot, polypeptide, prot bound steroid h, H+, HCO3

after spinal shock wears off 1st reflex-bulbocavernous(<2d)> flexor withdrawal> stretch reflex

CSF absorpt↑ ->112mmH2O↓ -<112mmH2O

Aim4a

iims.i

n

no-<68mmH2O

RSgeneration resp tract trachea-0 total=23 1st 16-conducting zone last 7-resp zone 1st 7-hyaline cartil last 16-no cartil, have sm m, gld, Kulchitsky cell, APUD cell 8-18-Clara cell 18-23-Achilles heel-mucociliary tpt weak max sm m-terminal bronchiole

→ → → → → trach principle bronchi bronchiole terminal bronchiole respirat bronchiole →acinus(alveolar duct alveolar sac)

pneumocyte typeI=60% in no., 5% of surf area typeII=40% in no., 92% of surf area(produce surfactant) typeIII=3% of surf area

anatDS-Fowler method-N2 analysis after 100% O2 inhalat PhyDS-Bohrs meth FRC-He dilut techniq, N2 washout meth, whole body plethysmography other-spirometry

ventilation start insp—peak insp—end expirat pressure(mmHg wrt atm) ITP-–2.5-–6-–2.5

→ → IPP-(0 –1)-0-(+1 0) TPP-+2.5-+6-+2.5

TPP=IPP–ITP ITP-intrapleural/pleural/intrathoracic press IPP-intrapulm/airway/alveolar press TPP-transpulm/distend/transmural press total press change during quiet resp= 2.5cmH2O deep sigh/yawn=–30cmH2O 1st cry neonat=–60cmH2O(25cmH2O) Muller maneuvre=–120cmH2O Valsalva maneuvre=+150cmH2O

O2 dissociat curve

Aim4a

iims.i

n

sO2—pO2 95-97 90-60 75-40

+ve cooperativity(DOTR)→ DeoxyHb OxyHb

→ Tense Relax Hill coeff n=1-no cooperativity n>1-+ve cooperat n<1-–ve cooperat

→ shift rt↑ -p50, pCO2, H+, temp, 2,3DPG, HbS, GH, exercise, T3,T4, altitude, furasol DA↓ -affinity, pH, Hb

↑ → BohR effect- pCO2-shift Rt(+1-2%O2 delivery) double Bohr effect-placenta, uterine a& umbilic a Haldane effect-deoxyHb can bind CO2& H+>oxyHb

↓ Hb affinity for CO- by HisE7

diffusion capacity of O2↑ -exercise, pulm hge, asthma, CHF↓ ↑ -ILD, sarcoid, berylium poisoni, secret of PDGF by alveolar epith

hypoxia→ pulm arteriole-activat K ch vasoconstrict

syst arteriole-vasodilat

zone standing II-Pa>Palv>Pv(waterfall zone)

III-Pa>Pv>Palv recumbent-zoneIII

matching of ventilat perfusion lung-lat decubitus, awake, close chest

resp centr medulla pacemaker-preBottzinger complex-generate resp rhythm DRG(nucl tract solitarius)-I-quiet resp sect at lower medulla-apnoea

↑ VRG(nucl ambiguous&retroambiguous )-I&E- requirem sect at upp medull-norm resp+ irregular rhythm+ gasping pons

Aim4a

iims.i

n

↓ Pneumotaxic(nucl Parabrachialis, upper pons)- depth of insp↑ midsectio(bel pnemotax)- depth,slow

↑ apneustic(lower pons)- depth of insp↓ CNX- depth of insp

strong vagal stim-apnoea↑ b/l vagotomy- depth,slow

midsection+b/l vagotomy-apneusis

resp chemorecept periph↓ ↑ pO2(MI,satO2<90%,pO2<60mmHg),pH, pCO2,H+, lactic acid, CN, exercise

→ glomus1-cup like ending aff n, NT-D2, O2 sensit K ch Ca influx glomus2-glia like, surround 4-6glomus 1 cell, no fn

↓ ↓ PCR remove-hypoxic drive -100%, CO2 drive -30%↑ ACh- chemorecept discharge carotid body

central surf of medulla↑ H+(mostpotent direct stim),CO2(most potent stim)

↓ COPD,hypoxic hypoxia- sensitivity to H+

resp reflex→↓ ↑ Hering Breuer inflation-lung inflat>1.0- 1.5l depth of insp, durat expirat

→ ↑ ↓ Hering Breuer deflation-mark deflation depth of insp, durat expirat→ ↓ Head paradoxical-inflat further inflat(1st breath neonat)

→ J recept(Dr ASPaintal,1970)-hyperinflat, pulm edema, pulm congest, pulm emboli → → → ↓ → ↓+J recept apnea rapid shallow resp BP HR

tidal resp-m spindle diaphr→ → ↑ ↑ jt propriocept +resp centr depth& rate of resp

Abbreviations a-artery, AA-amino acid, abtc-antibiotic, AI-autoimmune bef-before, bel-below, b/l-bilateral, bld-blood, b/n-between, bn-benign, br-branch, Bx-biopsy ca-carcinoma, carb-carbohydrate, c/i-contraindication, c/l-contralateral, conc-concentration, cong-congenital, Cx-cervix d-day, def-deficient, ds-disease, d/t-due to, Dx-diagnosis E-estrogen fem-female, fr-from gld-gland, glu-glucose h-hormone idiop-idiopathic, i/l-ipsilateral, inf-infection, inj-injury lig-ligament, LL-lower limb, l/t-leading to m-muscle, maj-major, mal-male, MC-most common, met-metastasis, min-minor, mtx-methotrexate, Mx-management n-nerve, norm-normal P-progesterone, pl-plasma, prot-protein, pt-patient

Aim4a

iims.i

n

Rx-treatment SCC-squamous cell carcinoma, sr-serum, Sx-surgery, sz-seizure tm-tumour, ts-tissue UL-upper limb, u/l-unilateral vag-vagina, VC-vocal cord, vel-velocity, vert-vertebra, vit-vitamin, vol-volume w-week, wt-weight Xr-X ray y-year #-fracture °-degree

THESE NOTES ARE ONLY FOR THE PURPOSE OF GUIDANCE AND HELP TO PG ASPIRANTS, NOT FOR COMMERCIAL OR OTHER PURPOSE. REFERENCE HAS BEEN TAKEN FROM VARIOUS STANDARD TEXTBOOKS.

Aim4a

iims.i

n