12.1 Applied Cardiovascular & Respiratory Physiology

12.1 Applied Cardiovascular & Respiratory Physiology

Cardiovascular Hemodynamics & Cardiac Cycle Mechanics

Understanding cardiovascular physiology requires mastering the mechanics of the cardiac cycle, ventricular compliance, pressure-volume loops, and systemic hemodynamic parameters. The core determinant of organ perfusion is Cardiac Output (CO), defined as the product of Heart Rate (HR) and Stroke Volume (SV) ($CO = HR \times SV$). Normal resting cardiac output ranges from 4.0 to 8.0 L/min. To account for variations in body size, the Cardiac Index (CI) adjusts cardiac output for body surface area ($CI = CO / BSA$), with normal values ranging between 2.5 and 4.0 L/min/m².

Stroke volume (normally 60–100 mL/beat) is determined by three interdependent variables:

1. Preload: The end-diastolic volume or wall tension of the ventricle prior to contraction. According to the Frank-Starling law, increasing end-diastolic volume expands myocardial fiber length, enhancing cross-bridge formation and stroke volume up to an optimal physiological limit. Left ventricular end-diastolic pressure (LVEDP) is clinically estimated by the Pulmonary Capillary Wedge Pressure (PCWP) (normal: 6–12 mmHg), while right ventricular preload is reflected by Central Venous Pressure (CVP) (normal: 2–8 mmHg).
2. Afterload: The ventricular wall stress developed during systolic ejection, governed by Laplace's law ($Wall\ Stress = \frac{Pressure \times Radius}{2 \times Wall\ Thickness}$). Left ventricular afterload is clinically reflected by Systemic Vascular Resistance (SVR), calculated using the formula: $SVR = \frac{MAP - CVP}{CO} \times 80$ Normal SVR ranges from 800 to 1200 dynes·sec/cm⁵. Right ventricular afterload is governed by Pulmonary Vascular Resistance (PVR) (normal: <2 Wood units or 50–150 dynes·sec/cm⁵).
3. Inotropy (Contractility): The intrinsic force of myocardial contraction independent of loading conditions. Enhanced by beta-1 adrenergic stimulation, extracellular calcium, and digitalis, inotropy shifts the Frank-Starling curve upward and to the left.

Pressure-Volume Loops & Cardiac Work

Ventricular performance is classically depicted using Pressure-Volume (PV) loops. Key landmarks include End-Diastolic Volume (EDV, ~120 mL), End-Systolic Volume (ESV, ~50 mL), and Stroke Volume ($SV = EDV - ESV = 70\text{ mL}$). The Ejection Fraction (EF) represents the proportion of blood ejected per contraction ($EF = SV / EDV \times 100%$, normal: 55–70%).

Changes in loading conditions produce distinct alterations on the PV loop:

• Increased Preload: Widens the PV loop rightward (increased EDV) with a modest increase in SV.
• Increased Afterload: Heightens the peak systolic pressure, increases ESV, and narrows the SV.
• Increased Contractility: Shifts the End-Systolic Pressure-Volume Relationship (ESPVR) slope upward and leftward, decreasing ESV and increasing SV.

Hemodynamic Profiles in Shock States

Differentiation of shock etiologies relies on invasive or non-invasive hemodynamic monitoring. The table below outlines the classic profiles tested on the MRCPI exam.

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Respiratory Mechanics & Ventilation-Perfusion (V/Q) Matching

Respiratory physiology focuses on pulmonary ventilation, gas transport across the alveolar-capillary membrane, and ventilation-perfusion matching throughout the lung zones.

The Alveolar Gas Equation & A-a Gradient

Alveolar partial pressure of oxygen ($PAO_2$) is determined by the Alveolar Gas Equation: $PAO_2 = FiO_2 \times (P_{atm} - P_{H_2O}) - \frac{PaCO_2}{R}$ On room air ($FiO_2 = 0.21$) at sea level ($P_{atm} = 760\text{ mmHg}$, $P_{H_2O} = 47\text{ mmHg}$) with a respiratory quotient ($R$) of 0.8: $PAO_2 = 0.21 \times (760 - 47) - \frac{PaCO_2}{0.8} = 150 - (1.25 \times PaCO_2)$

The Alveolar-arterial (A-a) Oxygen Gradient evaluates the efficiency of gas transfer: $A\text{-}a\text{ Gradient} = PAO_2 - PaO_2$ Normal A-a gradient on room air is <10–15 mmHg, or estimated as $(Age / 4) + 4$.

Causes of Hypoxemia Classified by A-a Gradient:

1. Normal A-a Gradient Hypoxemia:
   • Alveolar Hypoventilation (opioid overdose, neuromuscular weakness, CNS depression). $PaCO_2$ is elevated, but the lung parenchyma is normal.
   • Low FiO₂ (high altitude).
2. Elevated A-a Gradient Hypoxemia:
   • Ventilation-Perfusion (V/Q) Mismatch (pulmonary embolism, asthma, COPD, mild pneumonia). Responds readily to supplemental oxygen.
   • Right-to-Left Shunt (ARDS, severe lobar pneumonia, cyanotic congenital heart disease, pulmonary arteriovenous malformations). Refractory to 100% $FiO_2$ therapy because shunted blood bypasses ventilated alveoli.
   • Diffusion Impairment (idiopathic pulmonary fibrosis, systemic sclerosis ILD). Worsens significantly with exercise.

Oxygen Delivery & Hemoglobin Dissociation Dynamics

Total arterial oxygen content ($CaO_2$) accounts for hemoglobin-bound oxygen and dissolved oxygen: $CaO_2 = (Hb \times 1.34 \times SaO_2) + (0.0031 \times PaO_2)$ At normal values ($Hb = 15\text{ g/dL}$, $SaO_2 = 98%$, $PaO_2 = 90\text{ mmHg}$): $CaO_2 = (15 \times 1.34 \times 0.98) + (0.0031 \times 90) \approx 19.7 + 0.28 = 20\text{ mL } O_2/\text{dL}$.

Systemic Oxygen Delivery ($DO_2$) is calculated as: $DO_2 = CO \times CaO_2 \times 10 \approx 5.0\text{ L/min} \times 200\text{ mL/L} = 1000\text{ mL } O_2/\text{min}$

The Oxygen-Hemoglobin Dissociation Curve displays a sigmoidal shape due to cooperative binding. The P50 represents the $PaO_2$ at which hemoglobin is 50% saturated (normally ~26.8 mmHg).

• Right Shift (Decreased Affinity, Enhanced $O_2$ Unloading to Tissues): Higher P50. Induced by Acidosis ($H^+$ elevation), Hypercapnia (Bohr effect), Increased Temperature, and Elevated 2,3-Bisphosphoglycerate (2,3-DPG) (adaptive response to chronic hypoxia or anemia).
• Left Shift (Increased Affinity, Impaired $O_2$ Release): Lower P50. Induced by Alkalosis, Hypothermia, Decreased 2,3-DPG (stored blood transfusion), Carboxyhemoglobinemia (carbon monoxide poisoning), Methemoglobinemia, and Fetal Hemoglobin (HbF).

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Step-by-Step Arterial Blood Gas (ABG) & Acid-Base Physiology

Systematic blood gas interpretation follows a strict 4-step algorithm:

1. Assess pH: Normal: 7.35–7.45. Acidemia: pH < 7.35. Alkalemia: pH > 7.45.
2. Determine Primary Process: Compare pH with $PaCO_2$ (normal 35–45 mmHg) and $[HCO_3^-]$ (normal 22–26 mEq/L).
3. Calculate Expected Compensation:
   • Metabolic Acidosis: Winter's Formula: Expected $PaCO_2 = (1.5 \times [HCO_3^-]) + 8 \pm 2$. If measured $PaCO_2 > \text{Expected}$, co-existing respiratory acidosis exists. If measured $PaCO_2 < \text{Expected}$, co-existing respiratory alkalosis exists.
   • Metabolic Alkalosis: Expected $PaCO_2 = 0.7 \times [HCO_3^-] + 21 \pm 2$.
   • Acute Respiratory Acidosis: $[HCO_3^-]$ increases by 1 mEq/L per 10 mmHg rise in $PaCO_2$ above 40.
   • Chronic Respiratory Acidosis: $[HCO_3^-]$ increases by 3.5–4 mEq/L per 10 mmHg rise in $PaCO_2$ above 40.
   • Acute Respiratory Alkalosis: $[HCO_3^-]$ decreases by 2 mEq/L per 10 mmHg drop in $PaCO_2$ below 40.
   • Chronic Respiratory Alkalosis: $[HCO_3^-]$ decreases by 4–5 mEq/L per 10 mmHg drop in $PaCO_2$ below 40.
4. Calculate Serum Anion Gap (AG): $AG = [Na^+] - ([Cl^-] + [HCO_3^-])$ Normal AG: 8–12 mEq/L. (Adjust for hypoalbuminemia: add 2.5 mEq/L to AG for every 1.0 g/dL drop in serum albumin below 4.0 g/dL).

Diagnostic Framework for Metabolic Acidosis

MRCPI Exam Pearl: In High Anion Gap Metabolic Acidosis, calculate the Delta-Delta Ratio ($\Delta\text{AG} / \Delta HCO_3^-$): $\frac{\text{Measured AG} - 12}{24 - \text{Measured } HCO_3^-}$.

• Ratio < 0.4–0.8: Mixed HAGMA and Normal Anion Gap Metabolic Acidosis (e.g., severe diarrhea plus ketoacidosis).
• Ratio 1.0–2.0: Pure HAGMA (e.g., uncomplicated DKA or lactic acidosis).
• Ratio > 2.0: Pre-existing or co-existing Metabolic Alkalosis (e.g., severe vomiting plus DKA).