UPTAKE & DISTRIBUTION OF INHALATIONAL AGENTS GK 12/1/2018

INHALATIONAL AGENTS PATHWAY AIRWAY ALVEOLI BLOOD STREAM TISSUES METABOLISM ELIMINATION UPTAKE & DISTRIBUTION 12/1/2018

U & D – Some basics 12/1/2018

SOME BASICS……… Gases/vapors move from one phase to another along a partial pressure gradient Not along the concentration gradient Not along the volume gradient 12/1/2018

SOME BASICS……… Vapor moves from alveoli pul.capillaries systemic circulation tissues along the partial pr gradient only i.e. ---more pr. phase to low pr. phase till the equilibrium reached 12/1/2018

PARTITION -COEFFICIENT A ratio of volume of an anesthetic agent between two phases at equilibrium. Eg. Blood gas P-C of halothane 2.4 ……. Blood can hold 2.4 times of halo than alveoli at equilibrium …….Pr gradient will be maintained between alveoli & blood till 2.4 times of volume of halo move from alveoli to blood 12/1/2018

PARTITION -COEFFICIENT PC indicates…. Solubility of the agent in a medium / phase. Relative affinity of the agent to a phase Relative capacity of a phase to an agent. Eg. Blood gas P-C of halothane 2.4 ……. Blood can hold 2.4 times of halo than alveoli at equilibrium 12/1/2018

U & D – Bird’s eye view 12/1/2018

INHALATIONAL AGENTS PATHWAY AIRWAY ALVEOLI BLOOD STREAM TISSUES METABOLISM ELIMINATION RPG 75%C.O. MG 20%C.O. FG 5%C.O. 12/1/2018

equilibrium with in 10 min RPG BF- 75% c.o. MG 1-4hrs FG longer AIRWAY vent LUNG BF- 20% c.o. FG longer BF- 5% c.o. 12/1/2018

U & D Curve FA/FI 8 C AB-lung wash in B BC-RPG uptake phase C∞- MG,FG uptake phase A Time 12/1/2018

Brain anesthetic pr. Closely follows the alveolar pr. Alveolar pr is an index of brain tissue pr. Alveolar pr acts as a pressure head for maintenance of anesthetic tension at various sites. 12/1/2018

U & D – Closer view 12/1/2018

Factors concern with input Inspired anes.pr. Alveolar ventilation Factors concern with uptake from alveoli Uptake =λ Q (Pa-Pv) λ-solubility Q-cardiac output (Pa-Pv)-partial pr.gradient 12/1/2018

Solubility-a prime factor Expressed as partition coefficient Depending on solubility, Highly soluble-methoxyflurane15 > ether12 Moderately -halo2.5 > enflu1.8 > iso1.4 Poorly -sevo.69 > N2o.47 > des.42 Alveolar pr .inversely prop to solubility Induction inversely prop to solubility 12/1/2018

Solubility & Fa/Fi FA/FI Time Poor solubility Rapid induction Moderate solubility Fast induction High solubility Slow induction Time 12/1/2018

Cardiac output AIRWAY ALVEOLI BLOOD STREAM TISSUES CO removal from lung Fa/Fi—slow induction Fa/Fi—rapid induction 12/1/2018

Cardiac output & FA/FI FA/FI Time Low CO Rapid induction High CO Slow induction Time 12/1/2018

AV pressure gradient AIRWAY ALVEOLI TISSUES Blood flow TISSUES AV pr gradient is due to Tissue uptake AV pr gradient depends on 1.Tissue solubility [tissue blood PC] 2.Tissue BF 3.Arterial tissue pr. Gradient V A 12/1/2018

AV pressure gradient AV pr gradient is “O”-no tissue uptake-equilibrium achieved- in sequence-RPG-MG-FG Once brain tension equilibrated, uptake mainly by MG&FG tissues only. So, maintenance of lung & brain tension mainly depends on the uptake of anesthetic agent in muscle& fat. 12/1/2018

U & D Curve FA/FI 8 C AB-lung wash in B BC-RPG uptake phase C∞- MG,FG uptake phase A Time 12/1/2018

U & D –A little more -concentration effect -second gas effect 12/1/2018

Concentration effect The insp. anesthetic conc.[Fi] influences not only-the alveolar anesthetic conc.[Fa] -but also the rate of rise of Fa Rapid rise of Fa by 2 factors 1.concentrating effect 2.augmentation of inspired ventilation 12/1/2018

Concentration effect Concentrating O2 O2 O2 N2O O2 N2O N2O N2O 1% FG 60% 100% 100% 1% 1.7% 1.4% O2 O2 O2 31.7% 26.6% 19% N2O O2 N2O N2O 67% N2O 1% 8o% 50% of N2O taken up-40%of total gas FG O2 19% N2O N2O 8o% 72% Augmentation of ventilation Concentration effect

Concentration effect Uptake of half of N2O does n’t halve the concentration because the remaining gases are ‘concentrated’ in a smaller volume.[50% to 66.7%] The N2O uptake is filled by drawing more gases in to the lung [augmentation of inspired ventilation] the final N2O conc is 72% So, with 80% of N2O after 1 breath the alveolar conc[Fa] of N2O will be 72%[i.e. 90% of Fi] 12/1/2018

Concentration effect So, high Fi causes- Rapid rise of Fa High value of Fa The concentration effect clinically appreciated only in high concentration i.e. >20% 12/1/2018

Second gas effect The uptake of large volume of a first gas accelerates the alveolar & there by arterial rate of rise of a second gas [passively] administered concomitantly. 12/1/2018

Second gas effect The loss of volume due to the uptake of N2O concentrates the halothane-from1% to1.7%. Replacement of gas taken by the inspiration will augment the amount present in the lung i.e. the Fa of halo will be 1.4% The alveolar and brain tension of halo rise more quickly to wards the inspired tension when halo is given with N2O than With O2 only. 12/1/2018

Gases move from one phase to another along a partial pressure gradient Partition Coefficient indicates solubility, relative affinity & relative capacityof a phase to particular agent The intake of anesthetic agent determined by inspired pressure-Fi & alveolar ventilation 12/1/2018

The uptake = solubility × cardiac output × A-V pressure gradient During induction Fa serves as pressure head for the anesthetic tension thro’out body Highly soluble agent takes longer time to induce. 12/1/2018

Depending on perfusion, RPG will equilibrate with in 10 mins. MG & FG will equilibrate / try to equilibrate . Brain tension of an anesthetic agent almost always follows it’s alveolar tension {Fa} very closely &quickly. 12/1/2018

Recovery is just a reversal of what happens during induction. In decreased cardiac output states, alveolar & brain tension rise rapidly. Recovery is just a reversal of what happens during induction. 12/1/2018

Thank you 12/1/2018