Ch.

22 Respiratory physiology: the effects of anesthesia

1.Aerobic metabolism

Respirasi Seluler


2.Anaerobic metabolism

Fungsi utama paru-paru: Pertukaran gas antara darah & udara inspirasi hasil langsung dari metabolisme aerob sel yg menghasilkan kebutuhan konstan uptake O2 & eliminasi CO2

1. Metabolisme aerobik
Menggunakan O2, untuk mendapatkan energi. Karbohidrat, lemak, dan protein dimetabolisme menjadi dua fragmen karbon (asetil-KoA) dimetabolisme menjadi CO2, energi disimpan di NAD, FAD, dan GTP ditransfer menjadi adenosin trifosfat (ATP) melalui fosforilasi oksidatif. Glukosa : a. C6H12O6 + 6O2 6CO2 + 6H2O + energy b. energy + ADP + P ATP Menghasilkan 38 ATP c. Sebagian besar: ATP ADP + P + energy d. ATP: ADP = 10: 1 tetap terjaga. e. ATP, tidak dapat disimpan, tetapi terus diproduksi dan membutuhkan suplai substrat metabolik & suplai oksigen yang konstan

1.Aerobic metabolism

Respirasi Seluler

2.Anaerobic metabolism

Respiratory quotient (RQ) : Rasio jumlah produksi CO2 (CO2) terhadap konsumsi O2 (O2), dan umumnya menunjukkan jenis utama dari bahan bakar yang digunakan. a. RQ of carbohydrates, lipid, protein : 1.0, 0.7, 0.8 b. normal VCO2 : 200mL/min VO2 : 250mL/min normal RQ : 0.8 (Protein biasanya tidak digunakan sebagai sumber bahan bakar utama, lebih mencerminkan penggunaan kombinasi lemak dan karbohidrat.) c. VO2 = 10(weight) 3/4

2. Metabolisme Anaerobik
Menghasilkan sedikit ATP (2 ATP) Konversi glukosa: piruvat asam laktat

3.Efek Anestesi pada Metabolisme Sel

Anestesi umum biasanya mengurangi baik O2 dan CO2 sekitar 15% Penurunan terbesar adalah konsumsi O2 otak dan jantung

Anatomi Respirasi
1.Rib & musles

1. Rongga toraks dan otot2 respirasi

2.Trachea

Kontraksi diafragma: 3.Circulation a. Dasar rongga toraks turun sekitar 1.5 -7cm 4.innervation b. chest volume berubah 75% Otot bantu nafas ikut membantu ekspansi dada Otot yang bekerja saat inspirasi: SCM, scalene, pectoralis muscle. a. SCM : membantu pengangkatan rib cage. b. scalene : mencegah inward displacement of the upper rib saat inspirasi. c. pectoralis muscle : membantu ekspansi dada. Ekspirasi terjadi pasif pada posisi supine tapi menjadi aktif pada posisi tegak Exhalation: abdominal muscles (rectus abdominis, external and internal oblique, transversus) and internal intercostals pharyngeal muscle : penting untuk menjaga patensi jalan napas a. genioglossus, levator palati, tensor palati, palatopharyngeus, palatoglossus

Anatomi Respirasi
1.Rib & musles

2. Tracheobronchial

2.Trachea

Melalui struktur ini: konduksi aliran udara dari dan ke alveoli 3.Circulation 4.innervation Dichotomous division:membuat percabangan (2 cabang) dari trachea hingga alveolar sacs mencapai 23 division. Tiap alveolar sac memiliki 17 alveoli, total sekitar 300 juta alveoli dengan luas membran 50-100m2 Mucosa membentuk transisi gradual dari kolumnar bersilia menjadi kuboidal dan terakhir menjadi flat alveolar epithelium gas exchange : flat epithelium Jaringan kartilago makin berkurang patensi airway yg lebih kecil menjadi tergantung dari traksi radial oleh elastisitas dari jaringan sekitarnya;

Functional respiratory anatomy

 Alveoli 2.Trachea Alveolus diameter: 0.05-0.33 mm 3.Circulation a. Pada posisi tegak, largest alveolar: apex ,smallest : base 4.innervation b. Saat inspirasi perbedaan ukuran alveolar berkurang Dinding tiap alveolus diatur asimetris a. thin side (< 0.4 ) : gas exchange occurs, the alveolar epithelium and capillary endothelium are separated only by their respective cellular and basement membranes. b. thick side (interstitial space) (12 ) provides structural support pertukaran cairan dan zat terlarut terjadi ruang interstisial paru memisahkan epitel alveolar dari endotelium kapiler. ruang interstisial paru mengandung terutama elastin, kolagen, dan serat saraf
1.Rib & musles

respiratory epithelium two cell type type pneumocyte : flat and form tight (1-nm) junctions preventing the passage of large oncotically active molecules such as albumin into the alveolus type pneumocyte round cells that contain prominent cytoplasmic inclusions (lamellar bodies); contain surfactant; capable of cell division and can produce type I pneumocytes alveolar macrophages, mast cells, lymphocytes, and APUD cell, Neutrophils in smokers and ALI.

Functional respriatory anatomy

1.Rib & musles

3. Pulmonary Circulation & Lymphatics

2.Trachea

3.Circulation Dua sirkulasi, bronkial and pulmonal 4.innervation Sirkulasi bronkial a. Dari jantung kiri b. mempertahankan kebutuhan-kebutuhan metabolik trakeobronkial sampai bronkiolus pulmonal. Sirkulasi pulmonal a. dari jantung kanan melalui arteri paru-paru, yang terbagi menjadi cabang kanan dan kiri b. Darah beroksigen kemudian kembali ke jantung kiri oleh empat vena pulmonalis utama There are connections between the bronchial and the pulmonary circulations contributing to the normal venous admixture

Functional respriatory anatomy

Pulmonary Capillaries
Because of the relatively low pressure in the pulmonary circulation, the amount of blood flowing through a given capillary network is affected by both gravity and alveolar size The pulmonary capillary endothelium has relatively large junctions, 5 nm wide, allowing the passage of large molecules such as albumin. Circulating macrophages and neutrophils are able to pass through the endothelium prevent bacterial infection and to scavenge foreign particles

Pulmonary Lymphatics
originate in the interstitial spaces of large septa Large lymphatic vessels travel upward alongside the airways, forming the tracheobronchial chain of lymph nodes. Lymphatic drainage channels from both lungs communicate along the trachea a. left lung the thoracic duct b. right lung right lymphatic duct

Functional respriatory anatomy

1.Rib & musles 2.Trachea

4.Innervation

3.Circulation

Diaphragm is innervated by the phrenic nerves (C3-C5 nerve roots) 4.innervation a. Unilateral phrenic nerve block or palsy reduces most indices of pulmonary function (about 25%) b. accessory muscle activity c. Intercostal muscles are innervated by their respective thoracic nerve roots vagus nerves provide sensory innervation to the tracheobronchial tree sympathetic and parasympathetic autonomic innervation of bronchial smooth muscle and secretory glands vagal activity : bronchoconstriction , bronchial secretion a. sympathetic activity (T1-T4) : bronchodilation, decreases secretions b. nonadrenergic, noncholinergic bronchodilator system c. - and - adrenergic receptors are present in the pulmonary vasculature but the sympathetic system normally has little effect on pulmonary vascular tone

BASIC MECHANISM OF BREATHING

  reoxygenates desaturated blood & eliminate CO2 exchange of alveolar gas : brought about by small cyclic pressure gradients established within the airways. Spontaneous Ventilation
Pressure : alveoli > surrounding (intrathoracic) pleural pressure used as a measure of intrathoracic pressure P transpulmonary = Palveolar - Pintrapleural Diaphragmatic and intercostal muscle activation during inspiration expands the chest and decreases intrapleural pressure from 5 cm H2O to 8 or 9 cm H2O alveolar-upper airway gradient is established; gas flows from the upper airway into alveoli expiration, returns intrapleural pressure to -5cmH2O elastic recoil of lung : reversal of alveolar-upper airway gradient.

BASIC MECHANISM OF BREATHING

Mechanical Ventilation
positive airway pressure is applied. During inspiration, gas flows into alveoli until alveolar pressure reaches that in the upper airwa expiratory phase of the ventilator: the positive airway pressure is removed or decreased; gas flow out of alveoli.

Effects of Anesthesia on Respiratory Pattern

Efek anastesi pd pernafasan berkaitan dgn posisi & bhn anastesi. Bila pasien posisi terlentang dr posisi berdiri/duduk proporsi nafas dr rongga torak berkurang, lbh dominan pernafasan abdomen. Berkaitan dgn bhn yg digunakan anastesi ringan sering menyebabkan pola nafas ireguler a. inhalation agent : rapid & shallow b. nitrous-narcotic : slow & deep Induksi pd anastesi sering mengaktifkan otot ekspirator: ekspirasi aktif

MECHANICS OF VENTILATION
  The movement of the lungs is passive and determined by the impedance of the respiratory system Respiratory system is divided into the elastic resistance of tissues and the gasliquid interface, and nonelastic resistance to gas flow
elastic resistance of tissue and the gas-liquid : governs lung volume and the associated pressures under static conditions to overcome elastic resistance is stored as potential energy nonelastic resistance to gas flow : relates to frictional resistance to airflow and tissue deformation nonelastic resistance to overcome what is lost as heat.

MECHANICS OF VENTILATION
1.Elastic Resistance
Both the lungs and the chest have elastic properties The chest has a tendency to expand outward, whereas the lungs have a tendency to collapse recoil properties of the chest : due to structural components that resist deformation and probably include chest wall muscle tone recoil properties of the lung : due to their high content of elastin fibers and, the surface tension forces acting at the airfluid interface in alveoli.

Surface Tension Forces

a. b. The gasfluid interface lining the alveoli causes them to behave as bubbles Surface tension forces tend to reduce the area of the interface and favor alveolar collapse And half-proportional pressure = 2* surface tension Surfactant radius Alveolar collapse is therefore directly proportional to surface tension but inversely proportional to alveolar size pulmonary surfactant decreases alveolar surface tension

c. d.

MECHANICS OF VENTILATION
Compliance
Elastic recoil is usually measured in terms of compliance (C), which is defined as the change in volume divided by the change in distending pressure chest wall compliance (CW) is reduced because of the weight of the abdominal contents against the diaphragm lung compliance is defined as CL = change in lung volume change in transpulmonary pressure a. normal : 150-200mL/cm H2O b. A variety of factors, including lung volume, pulmonary blood volume, extravascular lung water, and pathological processes such as inflammation and fibrosis Chest wall compliance = change in chest volume change in transthoracic pressure a. normal : 200mL/cm H2O total compliance (lung and chest wall together) : 100mL/cm H2O 1 = 1 + 1 Ctotal CW CL

MECHANICS OF VENTILATION
2.Lung Volumes
important parameters in respiratory physiology and clinical practice Lung capacities are clinically useful measurements that represent a combination of two or more volumes. Functional Residual Capacity a. The lung volume at the end of a normal exhalation b. the inward elastic recoil of the lung approximates the outward elastic recoil of the chest c. can be measured by nitrogen wash-out or helium wash-in technique or by body plethysmography d. Factors known to alter the FRC Body habitus : proportional to height, obesity decrease FRC sex : reduced by about 10% in females posture : supine or prone position decrease FRC Lung disease: Decreased compliance of the lung, chest, or both is characteristic of restrictive pulmonary disorders diaphragmatic tone

MECHANICS OF VENTILATION
Closing Capacity
small airways lacking cartilaginous support depend on radial traction caused by the elastic recoil of surrounding tissue basal areas of the lung, is highly dependent on lung volume FRC=closing capacity: 44 th closing capacity: The volume at which these airways begin to close in dependent parts of the lung measured using a tracer gas (xenon-133) normally well below FRC Not affected by posture Increases with age

Vital Capacity
maximum volume of gas that can be exhaled following maximal inspiration Dependent on body habitus, respiratory muscle strength and chest lung compliance normal : 60-70mL/Kg

MECHANICS OF VENTILATION
3. Nonelastic Resistances
Airway Resistance to Gas Flow a. Gas flow in the lung is a mixture of laminar and turbulent flow b. laminar flow : consisting of concentric cylinders of gas flowing at different velocities Flow = Pressure gradient Raw(airway resistance) Raw = 8 * Length * Gas viscosity * (Radius)4 c. turbulent flow : random movement of the gas molecule down the air passage Pressure gradient = flow2 * Gas density Radius5 Resistance : is not constant but increases in proportion to gas flow. directly proportional to gas density and inversely proportional to the fifth power of the radius d. whether turbulent or laminar flow can be predicted by Reynold number Reynold number =linea velocity * diameter * gas density gas viscosity laminar flow <1000 : only distal to small bronchioles(<1mm) turbulent flow >1500 : larger airway e. total airway resistance : 0.5-2 Cm H2O/L/s largest contribution coming from medium-sized bronchi (before 7th generation) cause of increased airway resistance: bronchospam, secretion, & mucosal edema volume-related & flow-related airway collapse

MECHANICS OF VENTILATION
A. Volume-Related Airway Collapse
at low lung volume (loss of radial traction) small airway resistance increases airway resistance inversely proportional to lung volume

B. Flow-Related Airway Collapse

During forced exhalation, reversal of the normal transmural airway pressure can cause collapse of these airways (dynamic airway compression) a. two contributing factors generation of a positive pleural pressure a large pressure drop across intrathoracic airway equal pressure point : The point along the airways where dynamic compression occurs a. Beyond the eleventh to thirteenth generation of bronchioles where cartilaginous support is absent b. Emphysema or asthma, occurs in

C. Forced vital Capacity

exhalation that is as hard and as rapid as possible provides important information about airway resistance. FEV1/FVC : proportional to the degree of airway obstruction a. Normally, FEV1/FVC > 80% FEV1 & FVC : effort-dependent FEF25-75% : effort independent, more reliable measurement of obstruction

MECHANICS OF VENTILATION
4.Work of Breathing
Because expiration is normally passive ,both inspiratory & expiratory work of breathing is performed by the inspiratory muscles (primarily diaphragm) Three factors must be overcome during ventilation. 1. elastic recoil of the chest & lung 2. frictional resistance to gas flow 3. tissue frictional resistance respiratory muscle : 2-3% of oxygen consumption with 10% efficiency a. 90% of the work is dissipated as heat (due to elastic and airflow resistance) The work required to overcome elastic resistance increases as VT increases, whereas the work required to overcome airflow resistance increases as respiratory rate (and, necessarily, expiratory flow) increases

MECHANICS OF VENTILATION
5. Effects of Anesthesia on Pulmonary Mechanics
Effects on Lung Volume & Compliance a. induction : additional 15-20% reduction in FRC (400mL in most patients) - loss of normal end-expiratory diaphragmatic tone b. Closing capacity & FRC is reduced similarly to the anesthesia Effects on Airway Resistance a. The reduction in FRC associated with general anesthesia would be expected to increase airway resistance. however, because of the bronchodilating properties of the volatile inhalation anesthetics, Increases in resistance are not usually observed. Effects on the Work of Breathing a. Increases in the work of breathing under anesthesia are most often secondary to reduced lung and chest wall compliance.

VENTILATION/PERFUSION RELATIONSHIPS
1.Ventilation
minute ventilation = respirtory rate * tidal volume (VT) alveolar ventilation(VA) : respiratory rate * (VT - VD) dead space ( VD) : part of the VT not participating in alveolar gas exchange a. physiologic : anatomic dead space + alveolar dead space (nonrespiratory airway) (not perfused alveolar) b. Normally 150mL (approximately 2mL/kg) normal tidal volume is approximately 450mL VD : PACO2 - PECO2 : 33% VT PACO2 ( PACO2 : alveolar CO2, PECO2 : mixed expired co tension)

VENTILATION/PERFUSION RELATIONSHIPS
Distribution of Ventilation
unevenly distributed a. right lung > left lung (53% : 47%) b. lower area (dependent) > upper area (transpulmonary pr. high) alveoli in upper lung areas are near-maximally inflated and relatively noncompliant little expansion the smaller alveoli in dependent areas have a lower transpulmonary pressure, are more compliant greater expansion during inspiration. Airway resistance can also contribute to regional differences in pulmonary ventilation In reality, inspiratory time is limited by the respiratory rate and the time necessary for expiration an excessively short inspiratory time will prevent alveoli from reaching the expected change in volume alveolar filling dependent on both compliance and airway resistance.

Time Constants
lung inflation to the time constant can be represented mathematically.. t = total compliance * airway resistance Regional variations in resistance or compliance not only interfere with alveolar filling but can cause asynchrony in alveolar filling during inspiration.

VENTILATION/PERFUSION RELATIONSHIPS
2. Pulmonary Perfusion
approximately 5 L/min of blood flowing through the lungs, only about 70100 mL at any one time is within the pulmonary capillaries undergoing gas exchange Although capillary volume remains relatively constant, total pulmonary blood volume can vary between 500 mL -1000 mL. a. A shift in posture from supine to erect decreases pulmonary blood volume (up to 27% ) b. Local factors are more important than the autonomic system in influencing pulmonary vascular tone c. Hypoxia:stimulus for pul. vasoconstriction d. pul. arterial & alveolar hypoxia induce vasoconstriction : Increases leukotrienes, NO inhibition may play a role reducing intrapulmonary shunting and preventing hypoxemia e. hypercapnia & acidosis : contstrictor effect (hypocapnia vasodilate)

VENTILATION/PERFUSION RELATIONSHIPS
Distribution of Pulmonary Perfusion
lower (dependent) portion > upper portion a. zone 1 : PA>Pa> Pv alveolar dead space: because alveolar pressure continually occludes the pulmonary capillaries b. zone 2 : depending to arterial-alveolar pressure gradient c. zone 3 : depending to arterial-venous pressure gradient

Ventilation/Perfusion Ratios
alveolar ventilation (VA) : 4L/min pulmonary capillary perfusion : 5L/min V/Q rate : 0.8 (0 (no ventilation) infinity (no perfusion)) no ventilation : intrapulmonary shunt 0.3 < V/Q < 3.0 V/Q ratio relates to the efficiency with which lung units resaturate venous blood with O2 and eliminate CO2

VENTILATION/PERFUSION RELATIONSHIPS
3.Shunts
shunt : the process whereby desaturated, mixed venous blood from the right heart returns to the left heart without being resaturated with O2 in the lungs a. absolute shunt : anatomic shunt & V/Q is zero b. relative shunt : low but finite V/Q ratio

Venous Admixture
the amount of mixed venous blood that would have to be mixed with pulmonary end-capillary blood to account for the difference in O2 tension between arterial and pulmonary end-capillary blood venous admixture (Qs): expresseed as a fraction of total cardiac output (QT) : CcO2 - CaO2 QS QT CcO2 - CvO2 a. CcO2 : oxygen content of ideal pulmonary end-capillary blood b. CaO2 : arterial oxygen content c. CvO2 : mixed venous content Normal QS/ QT is primarily due to communication between deep bronchial veins and pulmonary veins, the thebesian circulation in the heart, and areas of low but finite V/Q in the lungs venous admixture in normal individuals (physiological shunt) is typically less than 5%.

VENTILATION/PERFUSION RELATIONSHIPS
4.Effects of Anesthesia on Gas Exchange
increased dead space, hypoventilation, and increased intrapulmonary shunting. There is increased scatter of V/Q ratios General anesthesia commonly increases venous admixture to 5 10%, probably as a result of atelectasis and airway collapse in dependent areas of the lung. Inhalation agents, including NO, also can inhibit hypoxic pulm. vasoconstriction in high doses PEEP is often effective in reducing venous admixture and preventing hypoxemia during general anesthesia Prolonged administration of high inspired O2 concentrations (> 50%) may be associated with increases in absolute shunt. a. complete collapse of alveoli with previously low V/Q ratios is thought to occur once all the O2 within is absorbed (absorption atelectasis).

ALVEOLAR, ATERIAL & VENOUS GAS TENSIONS

 gas mixture : each gas pressure proportional to its concentration
PIO2 = PB * FiO2 (159.6mmHg=760mmHg*0.21) PB = barometric pr. FiO2 = the fraction of inspirated oxygen a. Partial pressure in millimeters of mercury approximates the percentage x 7. b. Partial pressure in kilopascals is approximately the same as the percentage.

1. Oxygen Alveolar Oxygen Tension

1. 2. With every breath, inspired gas mixture is humidified at 37C in the upper airway. The inspired tension of oxygen (PIO2) is therefore reduced by the added water vapor PIO2 = (PB -PH2O) * FiO2 In alveoli, the inspired gases are mixed with residual alveolar gas from previous breaths, O2 is taken up, and CO2 is added PAO2 = PIO2 -PaCO2/RQ PaCO2 : arterial CO2 tension, RQ = respiratory quotient Large increases in PaCO2 (> 75 mm Hg) readily produce hypoxia (PaO2 < 60 mm Hg) at room air but not at high inspired O2 concentrations inspired oxygen concentration(%) * 6 = PAO2 mmHg

3. 4.

ALVEOLAR, ATERIAL & VENOUS GAS TENSIONS

Pulmonary End-Capillary Oxygen Tension (Pc`O2) 1. For practical purposes, Pc`O2 = PAO2 2. Pc'O2 is dependent on the rate of O2 diffusion across the alveolarcapillary membrane as well as on pulmonary capillary blood volume and transit time
capillary transit time = pulmonary capillary blood volume

cardiac output
= 70mL / 5000mL/min (0.8sec)

3. 4.

The binding of O2 to hemoglobin appears to be the principal rate-limiting factor in the transfer of O2 from alveolar gas to blood pulmonary diffusing capacity reflects not only the capacity and permeability of the alveolarcapillary membrane but also pulmonary blood flow
O2 transfer across the alveolarcapillary membrane is expressed as oxygen diffusing capacity (DLO2) DLO2 = oxygen uptake PAO2 Pc`O2 Pc `O2 can not be measured accurately used instead DLCO DLCO = carbon monoxide uptake PACO -Pc`CO Reductions in DLCO imply an impediment in gas transfer across the alveolarcapillary membrane a. due to abnormal V/Q ratio, destruction of alveolar-capillary membrane, short capillary transit time

ALVEOLAR, ATERIAL & VENOUS GAS TENSIONS

Mixed Venous Oxygen Tension
normal : 40mmHg Shows the overall balance oxygen consumption & oxygen delivery. Can be seen through pul. artery catheter. Mixed venous oxygen tension(PvO2) alterations

ALVEOLAR, ATERIAL & VENOUS GAS TENSIONS

Tekanan Karbon Dioksida Mix Vena (PvCO2)
Normal PvCO2 = 46 mm Hg merupakan hasil akhir pencampuran darah dari berbagai aktifitas metabolik jaringan

Tekanan Karbon Dioksida Alveolar (PACO2)

PACO2 secara umum mencerminkan keseimbangan total produksi CO2 dengan ventilasi alveolar (eliminasi). PACO2 = VCO2 VA

Tekanan Karbon Dioksida Pulmonary End-Capillary

Pc`CO2 = PACO2 Kecepatan difusi CO2 melalui membran alveolar-capillary 20 kali lebih cepat dibanding O2

Tekanan Karbon Dioksida Arterial (PaCO2

Normal PaCO2 adalah 38 4 mm Hg (5.1 0.5kPa); Prakteknya = 40 mm Hg.

Tekanan Karbon Dioksida EndTidal (PETCO2)

Secara klinis, PETCO2 digunakan sebagai perkiraan nilai PaCO2

TRANSPORT OF RESPIRATORY GASES IN BLOOD

1.Oxygen
O2 is carried in blood in two forms: dissolved in solution and in reversible association with hemoglobin.

Dissolved Oxygen
The amount of O2 dissolved in blood can be derived from Henry's law Gas concentration = * partial pressure =the gas solubility coefficient for a given solution at a given temperature The solubility coefficient for O2 at normal body temperature: 0.003mL/dL/mmHg

Hemoglobin
complex molecule consisting of four heme and four protein subunits Heme : ironporphyrin compound that is an essential part of the O2binding sites normal hemoglobin molecule (hemoglobin A1) a. 2 - & 2 -chain b. 4subunit berikatan lemah dengan residu asam amino Tiap hemoglobin 1g membawa 1.39mL O2

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Hemoglobin Dissociation Curve
Each hemoglobin molecule binds up to four O2 molecules Hemoglobin saturation is the amount of O2 bound as a percentage of its total O2-binding capacity The change in molecular conformation induced by the binding of the first three molecules greatly accelerates binding of the fourth O2 molecule At about 90% saturation, the decrease in available O2 receptors flattens the curve until full saturation is reached.

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Alkalosis

Factors influencing the Hemoglobin Dissociation Curve Hypothermia

Acidosis oxygen binding: hydrogen ion concentration, CO2 tension, temperature, and 2,3-DPG 2,3-diphosphoglycerate (2,3-DPG) concentrationHyperthermia P50 : the O2 tension at which hemoglobin is 50% saturated 2,3-DPG a. shift to right (increasing P50) P50 Affinity make more oxygen available to tissue O2 release to tissue b. shift to left (decreasing P50) O2 uptake . oxygen affinity increases, reducing availablity to tissue c. normal P50 : 26.6mmHg(3.4kPa) An increase in blood hydrogen ion concentration reduces O2 binding to hemoglobin (Bohr effect). 26.6mmHg CO2 tension : physiologically important a. CO2 tension secondary to the associated rise in hydrogen ion concentration when CO2 tension increases. 2,3-DPG is a by-product of glycolysis (the RapoportLuebering shunt) and accumulates during anaerobic metabolism a. play an important compensatory role in patients with chronic anemia b. significantly affect the O2-carrying capacity of blood transfusions

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Abnormal Ligands & Abnormal Forms of Hemoglobins
carbon monoxide, cyanide, nitric acid, ammonia can displace O2 and shift the saturation curve to the left carbon monoxide : 200-300 times affinity carboxyhemoglobin methemoglobin : iron in heme is oxidized to its trivalent (+3) form a. Reduction of methemoglobin to normal hemoglobin is facilitated by such agents as methylene blue or ascorbic acid. abnormal hemoglobin : variations in the protein subunit composition a. fetal hemoglobin, hemoglobin A2. sick hemoglobin

Oxygen Content
The total O2 content of blood is the sum of that in solution plus that carried by hemoglobin oxygen content = (0.003mL O2/dL blood/mmHg) * PO2 +(SO2 * Hb * 1.31mL/dL blood) CaO2 = 19.5mL/dL blood CvO2 = 14.8mL/dL blood arteriovenous difference can be calculated CaO2 -CvO2 = 4.7mL/dL

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Oxygen Transport
O2 transport is dependent on both respiratory and circulatory function Total oxygen delivery to tissue(DO2) = arterial oxygen content * cardiac output (QT) DO2 = 20mL O2/dL blood * 50dLper blood/min =1000mL O2/min The Fick equation expresses the relationship between O2 consumption, O2 content, and cardiac output oxygen consumption = VO2 = QT * (CaO2 - CvO2) CaO2 = VO2 + CvO2 QT extraction fraction : (CaO2- CvO2)/ CaO2 = 5/20 = 25% body normally consumes only 25% of the O2 carried on hemoglobin. When O2 demand exceeds supply, the extraction fraction exceeds 25%. Conversely, if O2 supply exceeds demand, the extraction fraction falls below 25%. When O2 is even moderately reduced, O2 usually remains normal because of increased O2 extraction

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Oxygen Store
normal O2 stores in adults are about 1500ml 1. oxygen remaining in the lung (FRC) : important store (80% available) 2. hemoglobin: terbatas 3. dissoluted in body-fluid : terbatas The remaining oxygen content = FiO2 * FRC a. FiO2 = 0.21 & FRC = 2300mL 90 terjadi severe hypoxemia. (O2 content=480ml) b. FiO2 = 1 & FRC = 2300mL 4-5 c. basis for preoxygenation prior to induction of anesthesia .

TRANSPORT OF RESPIRATORY GASES IN BLOOD

2.Carbon Dioxide transfort 3 form 1.dissolved in solution, 2. bicarbonate 3.carbamino compound protein Dissolved Carbon Dioxide
more soluble in blood than O2: 0.067mL/dL/mmHg

Bicarbonate
CO2 slowly combines with water to form carbonic acid and bicarbonate H2O + CO2 H2CO2 H+ + HCO3on the venous side of systemic capillary a. carbonic anhydrase within erythrocytes, systemic capillaries, CO2 enters red blood cells and is converted to bicarbonate. b. chloride ions move from plasma into red cells to maintain electrical balance in pulmonary capillary a. Pulmonarry capillaries, chloride ions move out of red cells as bicarbonate ions reenter them for conversion back to CO2, which diffuses out into alveoli. b. This sequence is referred to as the chloride or Hamburger shift.

Carbamino Compounds
R-NH2 + CO2 RNH-CO2- + H+ only a small amount of CO2 is carried in this form, mainly as carbamino-hemoglobin Deoxygenated hemoglobin (deoxyhemoglobin) has a greater affinity (3.5 times) for CO2 than does oxyhemoglobin.

TRANSPORT OF RESPIRATORY GASES IN BLOOD

Effects of Hemoglobin Buffering on Carbon Dioxide Transport
Hemoglobin can act as a buffer at physiological pH because of its high content of histidine the acidbase behavior of hemoglobin is influenced by its oxygenation state. Removal of O2 from hemoglobin in tissue capillaries causes the hemoglobin molecule to behave more like a base CO2 + H2O + HbO2 HbH+ + HCO3- + O2 In the lungs, the reverse is true. Oxygenation of hemoglobin favors its action as an acid O2 + HCO3- + HbH+ H2O + CO2 + HbO2

Carbon Dioxide Dissociation Curve Carbon Dioxide Stores

Carbon dioxide stores: 120L in adult primarily in the form of dissolved CO2 and bicarbonate When imbalance occurs between production and elimination, establishing a new CO2 equilibrium requires 2030 min

CONTROL OF BREATHING
Spontaneous ventilation is the result of rhythmic neural activity in respiratory centers within the brain stem

1.Central Respiratory Center

Basic breathing system originates from medulla, two medullary group of neuron 1.dorsal respiratory group : active during inspiration 2.ventral respiratory group : active during expiration basic rhythm  intrinsic spontaneous discharge activity in the dorsal group or reciprocating activity between the dorsal and ventral groups Two pontine areas influence the dorsal (inspiratory) medullary center to fine-tune respiratory rate and rhythm 1. lower pontine (apneustic) center : excitory 2. upper pontine (pneumotaxic) center : inhibitory

CONTROL OF BREATHING
2.Central Sensor (Chemoreceptor)
anterolateral surface of medulla a. respond to CSF (H+) changes b. effective in regulating PaCO2 (BBB is permeable to dissolved CO2) c. Increases in PaCO2 elevate CSF hydrogen ion concentration and activate the chemoreceptors. Secondary stimulation of the adjacent respiratory medullary centers increases alveolar ventilation and reduces PaCO2 very high arterial PaCO2 tensions depress the ventilatory response:CO2 narcosis PaCO2 at which ventilation is zero (x-intercept) is known as the apneic threshold contrast to peripheral chemoreceptors, central chemoreceptor activity is depressed by hypoxia

CONTROL OF BREATHING
3.Peripheral Sensor Peripheral Chemoreceptors
Pph. chemoRc Lung receptors

1. carotid bodies (at the bifurcation of the common carotid arteries) a. principal peripheral chemoreceptor in human b. Sensitive to changes PaO2, PaCO2, PH, arterial perfusion pressure c. interact with central respiratory centers via the glossopharyngeal nerves. d. Also stimulated by cyanide, doxapram, large dose of nicotine e. receptor activity does not appreciably increase until PaO2 decreases below 50 mm Hg. f. cell of the carotid body (glomus cell) : dopaminergic neuron cf) antidopaminergic drug, bilateral carotid surgery abolish the peripheral ventilatory response to hypoxemia 2. aortic bodies (surrounding the aortic arch)

CONTROL OF BREATHING
Lung Receptors
Pph. chemoRc Lung Receptor carried centrally by vagus nerve stretch receptor : distributed in the smooth muscle of airway a. responsible for inhibition of inspiration when the lung is inflated to excessive volumes (Herning-Breuer inflataion reflex) b. shortening of exhalation when the lung is deflated (deflation reflex). Play minor role in human irritant receptor( in tracheobronchial mucosa) J (juxtacapillary) receptors (interstitial space within alveolar wall) : interstitial space vol. these receptors induce dyspnea in response to expansion of interstitial space volume and various chemical mediators following tissue damage.

Other receptors
Meliputi berbagai macam otot dan reseptor gabungan pada otot paruparu dan dinding dada.

FUNGSI NONRESPIRASI PARU-PARU

Fungsi Filtrasi & Reservois
Posisi unik dari kapiler-kapiler paru-paru dalam fungsi sirkulasi memudahkannya untuk menyaring debris pada pembuluh darah

Metabolism
Paru-paru adalah organ yang secara metabolis sangat aktif. Endothelium paru-paru memetabolisme berbagai senyawa vasoactive, termasuk norepinephrine, serotonin, bradykinin, dan berbagai prostaglandins an leukotrienes.