Physiology B

• The A/C membrane is a fusion of the alvolar wall and the capillary wall.
• 0.5 to 1 um thick

Type I: flat, thin cells that make up about 95% of the gas exchange area.

Type II: Thick cells that produce surfactant

Type III: Free-floating macrophage-like cells

• a) 35-45 mmHg
• b) 80-100 mmHg
• c) 40 mmHg
• d) 46 mmHg

• PvCO₂-PaCO₂= 6 mmHg
• Enough to drive CO₂ from the capillaries to the alveoli (for removal)

• Hyperventilaiton: alkalosis.
• - O₂ and CO₂ near ammbient values (150 and 10 mmHg respectivley)

• Hypoventilation: acidosis
• - O₂ < 50 mmHg and CO₂ > 50 mmHg

0.003 mL/dL plasma/mmHg at 37'C

• A hemoprotein enzyme attatched to the endoplasmic reticulum in A/C membrance cells.
• - Facillitates the diffusion of O₂ accross the membrance (approx 10-15%)

Most notably known for its anti-toxic role in the liver

Can be increased up to 20% when in a recumbent position due to gravity:

• - when lying, blood supply is more evenly distributed accross lung fields (improved V/Q matching)
• - pulmonary blood volume increases as well

A measurement of the volume of a specific gas that can be transferred per unit time accross the A/C membrane (efficiency)

Normally 30 mL/O₂/min/mmHg gradient

• 1. prop. to the pressure gradient accross the mem.
• 2. prop. to the solubility of the gas in the mem
• 3. prop. to the rxn rate of O2 with Hb
• 4. prop. to the volume of blood in the capillary bed

• 5. inverse to membrane thickness
• 6. inverse to the molecular weight of the gas

• 1. Body Position:
• - inc with lying
• 2. Body size:
• - refers to natural size, not obesity
• - inc size = inc A/C size (inc V/Q interface)
• 3. Exercise:
• - inc (35%) during exercise
• 4. Disease:
• - emphysema: destroys alveolar and capillary tissue
• - pneumonia: consolidates gas exchange regions
• - pulmonary embolism: capillary blood flow obstruction
• - V/Q mismatch: when majority of blood flow is not in the same region as the majority of gas (usually due to the above)

• The gradient is formed by the difference in the partial pressures of O₂ and CO₂ between alveolar and capillary gas.
• Venous blood returning from the body is relativley low in PO₂ and high in PCO₂, which creates an ideal condition under which CO₂ can exit the body and O₂ can enter.
• The volume and rate of gas exchange is directly related the gas pressure gradient

The wall of each pulmonary artery is about 30% or 1/3 the size of the aorta

The pulmonary arteries and arterioles have relativley large diameters and thin walls= this allows for high compliance.

The Right ventricle is approximatley 30% or 1/3 the thickness of the Left ventricle.

This is a result of the pressure difference between the 2 systems (due to their requirements). The systolic pressure of the Right ventricle (pulmonary) is 25 mmHg compared to the 120 mmHg pressure of the Left (systemic) side.

The stroke volume output is approximatley 70mL and the compliance of the vasculature is about 2mL/mmHg.

• This means that with a normal systolic pressure of 25 mmHg, 50mL out of the 70mL's pumped out/beat can be accommodated by the vessels.
• This aids in keeping the circuit pressure relatively low (decreased force required).

About 1-2% supplies O₂ and nutrients for the lung-supporting tissues

• Once this supply passes through the tissues, it empties back into the pulmonary veins (not venous circ'n). = enters the Left atrium and mixes with oxygenated blood = anatomic shunt
• -note that this is one reason for the increased C/O of the Left ventricle

The primary cause of PE is elevated pulmonary capillary pressure (from cardiac failure).

For edema to occur, capillary bp must rise 2-3 mmHg above colloid osmotic pressure.

Because normally capillary P is 8 mmHg while colloid osmostic is 28 mmHg, there existst a 23 mmHg buffer before edema will occur.

This buffer region not only means capillary P has to climb a long way, but because it would take longer to rise above the buffer, the lymphatic system has more to compensate (by inc flow)

Hypoxia = vasoconstriction

Hyperoxia = vasodilation

Hypercapnia= vasoconstriction

Vascular pressures must increase as vascular caliber decreases. Resistance to blood flow increases with vasoconstriction and reduced with dilation.

• Hypoxia
• Hypercapnia
• Acidosis
• Sympathetic stimulation
• Pulmonary embolism
• Anaphylaxis
• alpha agonists...

• PWAP
• Pressure measure distal to the balloon catheter (once inflated) , through the capillary bed. Represents Left ventricular preload or Left ventricular end diastolic pressure (normally 5-12 mmHg)

• The zones are a model for describing variations in pulmonary perfusion (uneven distribution) due to gravity.
• When a person is standing, Bp can differ by 90 mmHg at the feet vs the heart and by 23 mmHg between the base and the apex of the lung (8 below, 15 above due to heart placement)

• Zone 1: Area of no blood flow (deadspace)
• - a result of pulmonary Bp < alveolar pressure = compression of the capillary around the vessel (closing it off)
• - usually only occurs during mech ventilation or reduced C/O

• Zone 2: Area of pulsatile blood flow
• - pulmonary arteriole pressure is great enough to overcome alveolar pressure during systole only
• - extends from 8cm above the heart level to the apex

• Zone 3: Area of continuous blood flow
• - from 8cm above the heart to the base.
• - both systolic and diastolic pressures overcome alveolar

2-10 mmHg

The A/C membrane is approx 75-100 m²

70-100 mL of blood interfaces with about 2L of gas (functional residual capacity)

G) all of the above

1. Alveolar ventilation: Ventilatory pattern must match the body's metabolic demands (recall hyper or hypoventilation)

2. Pulmonary capillary blood flow: As venous blood moves through a ventilated alveolus, gas exchange occurs rapidly and tapers off as the gradient decreases. When the demand for exchange is increased (i.e. exercise) a greater gradient is produced and the diffusion rate increases (as long as ventilation corresponds)

3. Chemical reactions: Gas carried by the blood is dependent on the erythrocyte and Hb

• O₂ = .003 mL/dL blood/mmHg @ 37'C
• CO₂= 0.067 mL/dL blood/mmHg @ 37'C

CO₂ is approx 20x more soluble

5-6 mL/hr/100g tissue

• -Lymph vessels arise from tissues around vascular and bronchial spaces
• -They flow into the hilium of the lung and empty into the Right lymphatic duct
• -Helps remove debris, particulate matter and fluids
• -Anything that increases interstitial fluid P or lymphatic pump activity will inc lymph flow out.

• 1. Valves
• 2. Smooth muscle tone
• 3. Vessel compression

• 1- Left ventricular failure
• 2- leaky capillary membrane
• 3- decreased plasma osmotic pressure (colloid)
• 4- fluid overload
• 5- increased pulmonary Bp/vascular resistance

• 1- cardiac output
• 2- pulmonary vascular resistance
• 3- pulmonary vascular compliance

(recall that RV C/O is 70mL and vasculature is thin with about 2mL/mmHg of compliance)

• 1- Alveolar ventilation (V)
• 2- Pulmonary ventilation (Q)
• 3- Matching of the two (V/Q)

* if V/Q matching is offset, the majority of blood flow is not in line with the majority of gas flow and diffusion capacity is severely hindered.

• a) 1:0
• b) 1:0
• c) 1:2
• d) 1: .05

1 mL/lb ideal body weight. (or 2mL/kg)

• = physiological V_D - anatomical V_D
• or
• PaCO₂- P_ETCO₂ / PaCO₂

• it increases V/Q
• V is in excess of Q

They both describe the relationship between CO2 production and O2 absorbtion

The respiratory exchange ratio deals with the rlsp in the lungs while the respiratory quotient deals with it at the cellular level.

Anatomical shunt: routes venous blood directly into arterial blood (=-venous admixture)

1- Thebesian veins: Drain a portion of coronary blood directly into the L ventricle = admixture. (coronary blood is supposed to empty into the R ventricle but a portion empties into the pulmonary veins where it mixes with oxygenated blood)

2- Bronchial circulation: 1-2% of arterial blood is used to supply lung tissue. Once it has been used it drains into the L atrium/ventricle = admixture.

3- Pleural circulation: System that supplies the visceral pleura with blood also drains into the L atrium/ventricle= admixture.

CIO₂= (PAO₂ x 0.003) + (1.34 x Hb)

PAO₂ = PP of alveolar oxygen

Physiological shunt= combined total of all shunts (capillary and anatomical)

• = Q_S/Q_T= _______(CIO2- CaO2)_______
• _________(CIO2 - CaO2) + (CaO2 - CvO2)

• Q_S= Shunted cardiac output
• Q_T = total cardiac output

Ex: (21-20)/(21-20)+(20-15)= 16.6

• a) 15 mL/dL
• b) 20 mL/dL
• c) .05 or 5%

CvO₂= (1.34 x Hg x Satv) + (0.003 x PvO₂)

• The blood sample for analysis is best taken from the pulmonary artery.
• Satv= saturation of venous blood (sat of Hb)

It takes 0.75 seconds for an RBC to pass through the pulmonary capillary bed.

May be reduced by 1/3 when cardiac output is significantly increased (i.e. exercise).

Due to absence of perfusion in the alveoli which does not normally exist in a healthy lung:

• Decreased cardiac output
• Pulmonary hypotension
• Pulmonary embolus

• The embolus would obstruct flow to pulmonary vasculature= decreased perfusion
• - would cause expired air to not take part in gas exchange

As the embolus increases in size, End-tidal CO₂ decreases (= increasing the difference between end-tidal and PaCO₂)

An area of hyperventilation (ventilation in excess of perfusion) with an increased V/Q

• Ideal, both blood flow and ventilation are matched with each other:
• = a balance or equilibriation between blood and gas in the alveoli.

• Normal pressures:
• PAO₂ = 100 mmHg
• PACO₂ = 40 mmHg

• Shunt effect= a region of higher perfusion than ventilation, resulting in blood leaving the lung before gas exchange is complete
• (= hypoventilated blood; gas values are off and V/Q is decresaed to 1:2)

• True shunt: vascular communication that bypasses circulatory channels. (i.e. if blood went from the R-L ventricle without entering pulm circulation)
• Capillary shunt: Bypassing the alveolar capillaries
• Anatomical shunt: normal shut used to route venous blood directly into arterial (venous admixture)= appox 1-3% of cardiac output
• Physiological shunt: Combined anatomical and capillary shunts = approx 2-6% total cardiac output. Note that anatomical values don't change so any increase is due to capillary shunting in the lung

• Normal:
• with a 5% shunt, 95% of blood has actual O₂ values of 20 mL/dL (CaO₂) and 5% has mixed venous content of 15 mL/dL (CvO₂):
• 95% x CaO₂ (20 mL/dL)= 19 mL/dL
• 5% x CvO₂ (15 mL/dL) = 0.75 mL/dL
• = 19.75 mL/dL of O₂ in arterial blood

• With a 30% Shunt (i.e. due to obstruction)
• 70% CaO2= 14 mL/dL
• 30% CvO2= 4.5 mL/dL
• = 18.5 mL/dL (a difference of 1.25 mL or 14.5%)

• 250 mL of O₂ consumed
• 200 mL of CO₂ produced

The partial pressure at which Hb is 50% saturated with oxygen

Shift to the right= Hb has decreased affinity for O₂

• - increased Temp
• - increased PCO2
• - increased [H+] / decreased pH
• - increase in 2,3 DPG

the opposite is true for increasing affintity

• 1- Dissolved in plasma: 5-10%
• 2- As carbaminohemoglobin: 20-30%, then carried by plasma proteins (25%) or by Hb (75%)
• 3- Bicarbonate: 60-70%
• a) Tissue: CO₂ and H₂O are coverted to H⁺ (which binds with Hb) and HCO₃^- (which diffuses into plasma).
• Cl- diffuses into the RBC to balance charges (chloride shift).
• b) Lungs: Cl^- out and HCO₃^- switch back where CO₂ and H₂O is again formed and diffuse out of the cell for gas exchange

• A conjugated protein (attatched to an iron pigment)
• 2 major components:

• 1) Heme: Iron centered (Fe), made of 4 pyrrol groups (C₄H₄NH) linked via methene (CH₂) bridges. There are 4 heme groups/hemoglobin molecule. Each heme can carry one O₂ molecule.
• - 2 states of heme:
• a) Ferrous (reduced, Fe²⁺): normal state, available to accept oxygen
• b) Ferric (+ reduced Fe³⁺)= Methemoglobin, cannot accept oxygen

• 2) Globin: A protein with 4 polypeptide chains (2 alpha, 2 beta).
• Acts as a buffer (acid-base balance)

A term used to describe a deficiency in red blood cells

• 1) Hemorrhage or rapid blood loss.
• 2) Aplastic anemia: bone marrow disfunction= lack of RBC production
• 3) Megaloblastic anemia: deficiency in erythroblast production= slow production of oddly shaped cells in insufficiant quantities
• 4) Hemolytic anemia: disorder with fragile RBC's that rupture.

• 1) Reduced blood flow: circulatory hypoxia
• 2) Anemia: decreased RBC's (4 types)
• 3) Hemoglobinopathies: Hb abnormalities
• a) Sickle cell anemia: abnormal substitution of an amino acid in the Hb molecule
• b) Thalassemia: defect if peptide production= smaller RBC's (microcytic) with low Hb content (hypochromic)
• 4) Cyanide poisoning: Blocks cytochrom oxidase= impeding the Krebs cycle
• 5) Carboxyhemoglobin: carbon monoxide poisoning (Hb has an affinity 200x greater for CO so any PCO > 0.7 mmHg is lethal)
• 6) Methemoglobin: reducing agents present in the blood state reduce Hb to its ferric state, where it can't accept O_2. (methemoglobinemia: disorder where the body doesn't produce enzymes to counter this reduction)
• 7) Sulfhemoglobin: When Hb binds hydrogen sulfide= can't accept O₂

Henry's Law of solubility

• Arterial:
• - 20 mL/dL
• - 98%
• - 49 mL/dL
• - 7.4

• Mixed Venous:
• - 15 mL/dL
• - 75%
• - 53 mL/dL
• - 7.3

Haldane's Law/Haldane effect

Desaturation of Hb with O₂ increases its affintity for CO₂

120 days

Then destroyed in the spleen, liver and red mone marrow

It's the mechanisms of transport between lungs-RBC,s and Tissue-RBC's.

Accounts for only 3.6% of transport in the body (represents degree of use at the tissue level or gas exchange)

• Men: 14-18 g/dL
• Women: 12-16 g/dL

Each gram of Hb can carry approx 1.34 mL of O₂

-Mechanism for O₂ transport as Hb must bind O₂ in the lungs (inc affinity) yet release it in tissues (dec affinity).

- The oxyhemoglobin dissosiation curve describes Hb's affinity for O₂ under various physiological conditions: Due to the Bohr effect (inc [CO₂] or [H+]= dec affinity for O₂) and the Haldane effect (dec O₂ saturation= dec O₂ affinity) - and visa versa for both effects.

• -i.e. local conditions affect Hb's affinity in a way that facilitates transport:
• - tissues (due to aerobic metabolism)= inc CO₂ and dec pH (inc H+)
• - lungs (after ventilation)= inc O₂ and inc pH

VT can be calculated from TI x flow

• TI= cycle time/I+E (total parts)
• cycle time = 60/RR= 60/12= 5
• TI= 5/6= .833
• VT= 0.833 seconds x 0.5 L/sec= .417 L or 417mL

P_Peak= pressure from resistance (P_TA) + pressure from compliance (P_Plat)

• P_TA= R x flow
• = 5 cmH2O/L/sec x 60 L/min (or 1L/sec)
• = 5 cmH20
• P_Plat= V_T/Compliace
• V_T = T_I x flow
• (T_I= cycle time/I+E= 5/6)
• = .833 sec x 1 L/sec= 833 mL
• = 833 mL/25 mL/cmH₂O= 33.32 cmH₂O

Ppeak= 5 cmH₂O + 33.32 cmH₂O= 38.32

• Fever
• shivering
• seizures
• pain

• If the patient is morbidly obese, pregnant or has significant ascites, the abdominal organs or fluid can press against the diaphram when in a lying
• position.
• This may cause considerable resistance to inhalation and require increased work to achieve a desired tidal volume

Flow triggering or pressure triggering are two different breath initiation settings.

• Flow triggering is generally seen as requiring less patient effort to initiate
• a breath as it requires less negative flow

• Asthma patients may need longer exhalation times (T_E) to prevent worsening hyperinflation.
• An I:E ratio of 1:4 would be a recommended ratio to use

• High tidal volumes can result in ventilator-induced
• lung injury (VILI) as a result of either barotrauma and/or vulutrauma.

VILI can alter capillary permeability and lead to alveolar flooding

• PEEP helps to increase the volume of gas remaining in the lungs after exhalation.
• = This prevents the de-recruitment of diseased
• alveoli and maintains an even distribution of gas throughout the lungs, resulting in maximal oxygen uptake and preventing over-distension of healthy
• alveoli
• Also, helps with the redistribution of lung water.