Overview:

Transmission: Gap junctions, synaptic, para/auto-crine/endocrine

A: Proprio,motor -12-20(70-120m/s)
A: Touch,pressure -5-12(30-70m/s)
A: Motor spindle -3-6(15-30m/s)
Ae: Pain,temp - 2-5(12-30m/s)
B: Preganglionic <3(3-15m/s)
C: Dorsal root 0.4-1.2(0.5-2m/s)
C Postgang Symp 0.3-1.3(0.7-2.3)
RMP: -60 to -90 Smooth muscle RMP: -55mV
Plasma: 5% (NaK,ClHCO3Prot) [5% in capillaries]
Interstital fluid: 15% (NaKClHCO3) (between cells)
(extracellular 20%)
Intracellular fluid 40% (phos,Prot,KNaCl), (within cells)

Respiratory
18% of low pressure blood
>30um-nasopharynx. 5-10um conduct 2-5um bronchioles
airway mucosa secrete IgA,SP,definsin,proteases
Respiratory zone= last 7 divisions (11,800cm2)
Type 1 cell = flat + cytoplasm - lining cells 95%
Type 2 cell = granular pneumocytes - thicker & contain lamellar/ Produc
surfactant
Diaphragm = 75% of vol phrenic C3-5
Inter pleural pressure -2 to -6mmHg (-30mmg) inspiration
TV=500-750ml quiet breathing
IRV ~2L max inspiratory effort
ERV ~1L max active expiration after passive expiration
RV ~1.3L air left after max exp effort
TLC = ~5L TV+IRV+ERV+RV
VLC = TV+IRV+ERV
FRC = ERV+RV (airway resistance)
VC = IRV+TV+ERV
Helium measures RV

Henderson: pH = pKa + log[A-]/[HA]

Osmotic pressure (P)=nRT/V
Osmoles= MW/(#free moving particles)
Osmolality=Osmoles/kg of solvent
Osmolarity=#of osmoles/L of solution (Temp)
Gibbs-Donnan: Diffusable ions distribute themselves via conc gradient at
equilibrium
Nerst=Electrical potential based on conc gradient & elec gradient
Tight Junction = Zonula occludent (apical lamina)
Zonula adherens (microfil + cadherins)
Desmosomes (int fibres)
Gap junctions
Hemidesmosomes (basal lamina)

Obstructive = FEV1+FVC (FEV1/FVC=low) COPD/Asthma

Restrictive = FEV1+FVC (FEV1/FVC=Normal) Pul Fibrosis
Hysteresis = differences between pressure curves inf vs def
Anatomic dead space = does not include alveoli
Physiological dead space = inc alveoli. Co2 not exchanged
Bohrs = PECO2xVt=PaCO2x(TV-Deadspace)
PO2=Fi02Xbarometric pressure
Pul Cap pressure = 10mmHg
Pul Onc pressure = 25mmg
Diffusion = Finks law ~area,diffusion constant, pressure, thickness

Autonomic:
Tyrosine>DOPA>Dopamine>NORAD>Epi
M1=CNSGqIP3DAGintracell Ca
M2=cardiacKc open,Giinhibition of ADYCKccAMP
M3=Gland,smooth muscleGqIP3DAGintracellular CaConstriction
A1=Smooth muscleGqPL-CIP3DAGCa
A2=Adrenergic N terminals,plateletsGixADYCcAMP
B1=HeartGsADYCcAMP
B2=Cardiac, smooth muscle vessels GsADYCcAMP
D1=brain, renal bed
Sympathetic: Long PS/ShortPostS. aka thoracolumbar
VentralWRCsymp gang(chain)effector
Parasymp:ShortPs/LongPostS.Craniosacral(s2,3,4)
Edinger-Westphalciliary gangliaciliary
Small gangliaconstrictor iris
Nucleus ambiguusSA/AVnodes
Small vesicles: ATP/NORAD
Large vesciles: NPY (vasoconstrict)
Substance P,histamine,ANP,VIP = vasodilation

Hb: TO2Relaxedaffinity
Bohr effect = decreased pH O2 affinity due to deoxy binding H+
2,3DPG= product of glycolysis - charged anion that binds deoxy affinity
Temp: temp affinity
Affinity of CO is 210x O2

MSA=preganglionic autonomic neuron failure in SC/BS

luminal muscosa|submucosa plexus|circular|myenteric|longitudinal
Mr Blockade=Tropocamide. NT inact=Edrophonium. NT storage=Resperpine

Respiratory control centre: medulla Pre-Botzinger complex

Chemoreceptors carotid & aortic bodies - Type 1 cells discharge 2 hypoxiaclose K+ channels, Ca influx. Also stim by H+ PCo2 PO2
ventral medullar chemoreceptors detect H+
Haring-Breuer reflex: Inspiration Expiration (slow adapt mylin)
C-fibres = unmyelinated juxtapaillary receptors activated by hyperinflation/
capiscum (fast)
Haldane effect: Hb buffers H+, also binds CO2carbamino compound
Chloride shift HCO2:Cl exchanger 2 carbonic anhydrase
TracheaBonchibronchioleterminalresp bronchalevolar ductsacs

CVS:
Sympathetic = stellate ganglion
Noradrenergic = epicardial
Vagal = endocardial
Phase 0: Rapid depol 2 INa
Phase 1: Closure of INa
Phase 2: Plateau ICa + IK
Phase 3: IK
Phase 4: RMP -90mV
Pacemaker: Ih(Na/K)-60mVICaT-40mVICaLCa/KRepol
Vagal M2=GicGMP/IKachICa
B1=GsADYCcAMPICaL

Wallerian degeneration
Fast orthograde transport = 400mm/day
slow = 0.5-10mm/day
Neuron RMP = 70mV threshold = -55mV
Small & clear = Ach, glycine, GABA, glutamate ATP
Small & dense = catecholamines
Large & dense = neuropeptides, neuropeptide Y, vasopressin, enkephalin

LBBRBBseptumapexventricular wallAV
grooveendocardiumepicardiumbasalLV/pulconus/upper septum
SA0.051m/sAV0.05BH1m/sPurkinji4m/sVM1m/s

AMI:Abnormallyrepol 2 IK ST(seconds)RMP2Intracell K TQ/

ST(mins)Depol of fibresST(30min)dead muscle ECG silent (days)

Glutamine (Glutaminase) Glutamate (Glut decarboxylase) GABA

GABAa/bICl(CNS)
GABAcGPCRIK/ACycCa (retina)
-Ketoglutarate (Krebs)(GABA-T)Glutamate (substanceP)
AMPA/Kainiteligand INaFast EPSP
NMDAINa+ICaSlow EPSP
mGluRIP3DAG or cAMP

K: RMP-75mV, Vmax 2INa, Threshold potential, AP 2Phase2/sharper

Phase3. K>5.5Tall T-wave, K>6.5conduction K>7 flat P waves 2 atrial stun
K>8QRS fusing

Glycine
NMDASensitivity to Glutamate
GlycineRICl

ASys+30%Vol+AwaveIsovol, Vent P>AtrialAV close, CwaveVent

pressure>aortic(80mmHg)+Pul(10mm) AP valves open (125/25mmHg). 70-90mls
ESVV=50mls. 70-90mls/HR EDVV=130mlsPropodiastole~0.04sIsovol relax
AP valves close V-waveDiastole AV open 70%fill

Tyrosine (hydroxylase) into axon Na:T channelTyrosine

hydroxylDOPA(decarboxylase)Dopamine[VMAT](hydroxylase)
NORADEpinephrine
Taken up by NET. Metab by MAO

LV output=O2 consumption/[Ao2-Vo2]
Frank Stirling = SV x VEDV
Haemoglobin A=22 Fetal=22 - binds 2,3BPG less avidly.
Flow=P/R
Renauld<2000=laminar >3000=turbulent flow
Velocity(Q)=AxVellocity
Flowr4
Pressure0.77mmHg/cm above/below heart
RVLM. Baroreceptors=carotid/aortic archNTS.
Chemosensative Vagal C = Bezold-Jarisch reflex
Peripheral arterial chemoreceptors = PaO2/PCO2+pH
NO via gCYCcAMPCaVasodilation
Endothelin1=vasocontrictor//

Intrafusal=parallel to extrafusal
APSMT-tublesCa channel cisternsDHPR(RyR cardiac) SR releases
CaBinds TropCTrop-I exposes Actin siteActin&Mysoin crosslinkADP
releasedmovementATP bindsRecocksrepeat until Ca
ReabsorbedSERCATrop-C releases Ca
A band constant. Z lines move closer
TypeI=SO(red), TypeII=FOG,(Red)TypeIIb=FG(white)
Cardiac: Ca+calmodulinMLCKMLC binds to actinXB
T-system Skeletal muscle@AI, cardiac@Z
IA=x3, GroupII=NC+SB,Dynamic=Dynamic bags,static=chain/static

GPCR:mu endorphines>enkephalins>dynorphins
delta: enk>endo>dyn kappa: dyn>>endo>enk
Dopamine
D1cAMP
D2cAMP
Meissner=encapsulated dendrite-texture/slow vib rapid adapting
Merkel=exp dendritic ending- sustained pressure/touch/Slow adapt
Ruffini=exp dendritic-sustained pressure/slow adapt
Pacinian=unmylinated deep pressure/fast vib/Rapid adapt
First pain = glutamate. Second pain = Substance P
Warmth=C fibre cool=Ae
Sensory:FasciculusGracilis/cuneatusDCmedullaGCnucleiXmedial
leminiscusVPostLnucleus
Noiception:dorsalhornXascend Ventrolat Spinothalamic PthWayVPL
CSF - 60% prod choroid plexus. 90-150ml vol. 550ml per day
Na=Na,K4.6=2.9,Mg1.7=2.4,Ca5.0=2.5,Glu92=61,AA2.3=0.8,
Spinal cord: Autoreg(MAP60-150),Co2 linear(20-80),Hypoxia(<60)
Spinal:SC/Supraspinous tissue/interspinous lig/ligamentum flavum/dura/epi/lig
CVO2=49ml/min6-7%perC Isoelectric at 20c CMRO2~20%of TB at rest
ICP=5-15mmHg
CBF=CPP-CVR
CPP=MAP-ICP

Immunology
Classic pathway-trigger by immune complex
mannose-binding lectin path: lectin bins mannose in bacteria
Alternative/properdin: tigger by virus, back,fungi,tumor
Complement kills via insertion of porins
Innate=via TLR. TLR4+CD14=bacterial sepsis
Granulocyte
- cytoplasmic granules which responsible for inflammation & allergic
reactions
- Neut t=6hrs
- chemotaxisroll+selectinintegrindiapedesis
- Opsonisation IgE/complement
- Eosinophils:mucosa of GIT. IL3,5,GM-CSF.Parasites
- Basophils: release histamine 2 IgE
Mast Cell
- Degranulate in response to IgE. Release histamine + TGF-
Monocytes
- From BM T72hrsenter tissuebecome macrophages
Lymphocytes
- Only 2% are in circulation at any time (total 20-40% WCC)
- B-Cells: plasma cells, memory B-cells
- Activated plasma B secrete antibodies
- IgA=secretions IgD=antigen recognition IgE=release histamine from
mast/basophil IgG=complement activation,, IgM=complement,,
T-cells:
- cytotoxic CD8, bind MHC1
- helper(CD4) TH1=IL2, -inteferon, TH2=IL4,5 Bind MHC2
- memory cells
Antigen recognition:bind to BcellR(APC)digestpresent MHC as
HLApresents to helper T-celldivide+clonal selection
APC=Dendritic cells(LN,spleen),Langerhans(skin)
Class I = 45kDA Heavy Chain target mutant/viral proteins
Class II antigen = 29kDA chain target extracellular proteins
Type1=immediate allergy CD4Th2Bcell activateIgE
Type2=Cytotoxic. Antigens bind to own cell surfaces via IgG IgM
Type3=Unable to clear small immune complexes which accumulate IgG
Type4=delayed hypersensitivity. CD4CD8 (T-cells)
Type5=autoimmune against receptors IgG IgM
Insulin - tyrosine kinase activity
NO - increases cGMP
Slow EPSP = AcH + Musc Receptor
Aorta = 2%

Plasma: 5% (NaK,ClHCO3Prot) [5% in capillaries]

Interstital fluid: 15% (NaKClHCO3)
(extracellular 20%)
Intracellular fluid 40% (phos,Prot,KNaCl)
interstitial cells = EPO
Renal blood flow = 625ml/min
Relation of mesangial cells = dopamine.
Glomerulus
Proximal convoluted Tubule
- 65% of Na & H20 reabsorbed
- NaHE lumen / SGLT2 GLUT2 (GLUT1=brain)
- H+ binds to phosphate NaHPO4
- NaHCO3 Transporter +NaKAPase basolaterally
- Carbonic Anhydrase
- Glutamine converted into 2HCO3 + 2NH4NaNH4E
Thin descending tubule
- some H2O reabsorption. No NaCL
- AQ1
Thick ascending
- 25% Na
- Na/K/2Cl(NKCC2)
- NaHE lumen
Distal tubule
- 10%NaCl <5%H2O
- H+-ATPase lumen (intercalated disc)
- Carbonic anhydrase
- HCO3ClE basolaterally
- NaCl NCC
collecting tubule
- H+-ATPase lumen (intercalated disc)
- Carbonic anhydrase
- NH3 diffuses into tubule binds with H+ to form NH4+
- ENaC (tubular lumen)
- Aquaporin2 - vasopressin(ADH)
- NaKATPase - stimulated by aldosterone
- H2O 2-10%
collecting duct
PT: 66%Na,85%HCO3,65%K,60%H2O.NaHE3,SGLT2
TALH:25%Na,Na/K/2Cl(NKCC2)
DCT:10%NaCl NaCl cotrans(NCC)
CT: 2-5%NaCl. Principal-NaKatpase,ENac. Intercalated HAtpase,ClHCO3X
Vasopressin: AQP2
Acetazolamide:PCT inhibits carbonic anhydrase blunting NaHCO3
reabsorption. Alkaline diuresis, hyperchloremic metabolic acidosis
Dapagliflozin: PCT inhibits SGLT2.
Caffeine: PCT inhibits NHE3 via Adenosine A1r antag.
Frusemide: TALH inhibit NKCC2. HypoK,Mg,Ca, hypoK metabolic alk.
HyperUricaemia
Hydrochlorothiazide: DCT via Na/Cl NCC. Blunt uric acid secretion.
Enhance Ca absorption. HypoNa, Dyslip, Glucose intol.
Spironolactone: CT, down reg ENaC via Ald Receptors. ADR
hyperK,hyperchol metabAcid,gynecomastia.
Amiloride: Inhibit ENaC