physiology things i missed

Adrenergic drug

sympathomimetics/adrenomimetics

mimic the effect of NE and epinephrine or block adrenergic receptors

Cholinergic drugs

Parasympathomimetics

Mimics effects of ACh or block cholinergic receptors

Phenylephrine

Adrenergic drug

Alpha 1 agonist

Propranolol

Adrenergic drug

Muscarinic agonist

Atropine

Cholinergic drug

Muscarinic antagonist

Hexamethonium

Cholinergic drug

Nicotinic antagonist

Nicotinic Receptors (nAChRs)

• Located in autonomic ganglia (sympathetic and parasympathetic) and at the neuromuscular junction of skeletal muscle.

• Activation by ACh leads to depolarization and excitation.

Muscarinic Receptors (mAChRs)

• Located on effector organs innervated by parasympathetic postganglionic neurons (and some sympathetic targets like sweat glands).

• 5 subtypes (M1-M5)

• Activation by ACh can be excitatory or inhibitory, depending on the subtype and target organ (e.g., slows heart rate (M2M2​), stimulates smooth muscle contraction).

Adrenergic Receptors

• Located on effector organs innervated by postganglionic sympathetic neurons.

• Two main types: Alpha (αα) and Beta (ββ), each with subtypes (α1,α2,β1,β2α1​,α2​,β1​,β2​).

• Activation by NE or Epinephrine produces various effects:

  • α1​: Vasoconstriction of blood vessels.

  • α2: Inhibits release of norepinephrine (negative feedback).

  • β1​: Increases heart rate and force of contraction.

  • β2​: Relaxation of smooth muscle in bronchioles, uterus, and peripheral blood vessels.

Nitric Oxide (NO)

• Some parasympathetic nerves (and other non-adrenergic, non-cholinergic neurons) release Nitric Oxide (NO) as a neurotransmitter.

• diffuses through cell membranes to activate intracellular

• Made more active by Sildenafil (Viagra)

Emphysema

Destruction of alveolar walls

What is Pulmonary edema

What is Fibrosis

Fluid in interstitial space

Scarring

Diffusing Capacity (DLCO)

This is calculated as the volume of carbon monoxide (CO) inhaled per minute divided by the pressure gradient between the alveoli and the capillary blood.

Decrease DLCO

Emphysema (↓ surface area), pulmonary fibrosis (↑ thickness), pulmonary embolism (↓ blood flow), anemia (↓ Hb concentration).

Increase DLCO

Exercise (↑ surface area), supine position (↑ blood flow), polycythemia and high altitudes (↑ Hb concentration).

Partial pressure of O2 (PO2) in dry inspired air

0.21 × 760 =160mmHg

PO2 of humidified air

0.21 x (760-47)=150mmHg

PO2 of Alveolar Air

PAO2=(Pamt - 47)FiO2 - PACO2/R

PAO2 = (760-47)0.21 - 40/0.8

(760-47)0.21 - 40/0.8 =100 mmHg

PO2 of arterial blood

100

PO2 of mixed venous blood

40 cuz its delivering blood

PO2 of tissues

Less than 30

Hypoxia

Insufficient oxygen supply to the tissues, meaning tissues do not receive or cannot utilize enough oxygen.

Breathing is stimulated when PO2​ drops below 60 mmHg.

Hypoxemia

Low oxygen levels in the arterial blood (\(\text{PaO}_2 < 60 \, \text{mmHg}\)). Hypoxemia is a common cause of hypoxia.

Hypoxic (Hypoxemic) Hypoxia

Deficient oxygenation of arterial blood. Causes include:

• Low inspired (high altitude), Hypoventilation, Impaired diffusion, Right-to-left shunts, Ventilation-perfusion inequalities.

Anemic Hypoxia

Insufficient number of functional red blood cells or hemoglobin to carry oxygen. Causes include:

Anemia, Abnormal Hb

Stagnant Hypoxia

Reduced oxygen delivery to tissues due to inadequate blood flow. Causes include:

Generalized: Congestive heart failure.

Localized: Obstruction of blood vessels.

Histotoxic Hypoxia

Tissues are unable to utilize oxygen, despite adequate delivery, due to poisoning of cellular enzymes involved in oxygen metabolism. Cause:

• Cyanide poisoning.

Alveolar-Arterial Oxygen Gradient (A-a Gradient)

- widened gradient

- response to O2 (good or poor)

• Normal Gradient: Typically less than 12 mmHg on room air.

• Widened Gradient: Indicates hypoxemia (PO2 normal or near normal while PaO2 is reduced)

• Response to Oxygen:

  • Good response: Hypoxemia due to hypoventilation or low inspired generally improves significantly with supplemental oxygen.

  • Poor response: Hypoxemia due to shunts is poorly responsive to oxygen therapy because the blood bypasses the lungs

Type 1: Hypoxic Respiratory Failure

Characterized by hypoxia without hypercapnia (PaO2 < 60). Often caused by impaired oxygenation (e.g., pneumonia, pulmonary edema).

Type 2: Hypercapnic Respiratory Failure

Characterized by hypoxia with hypercapnia (PaCO > 50). Often caused by alveolar hypoventilation due to respiratory muscle weakness or central respiratory depression.

Boyles law

When vol increases pressure decreases

Inversely proportional

Dalton's Law of Partial Pressures

The total pressure exerted by a mixture of gases is the combined pressure exerted by each gas.

Henry's Law

The higher the partial pressure of a gas above a liquid, the more of that gas will dissolve into the liquid.

Hb structure

2 alpha and 2 beta polypeptide chains

Globin chains can bind to CO2 and hydrogen ions

2,3-bisphosphoglycerate (2,3-DPG) binds to beta chains

Deoxygenated Hb (deoxy-Hb)

is in a "taut" (T) state, stabilized by salt bridges between subunits.

Oxygenated Hb (oxy-Hb)

is in a "relaxed" (R) state. Binding of O2O2​ causes the iron atom and proximal histidine to move into the plane of the porphyrin ring, breaking salt bridges and leading to a conformational change

P50

The partial pressure of O2​ at which Hb is 50% saturated. In healthy individuals, it is approximately 26.6 mmHg. It is a measure of Hb's affinity for O2

Right Shift (Decreased Affinity, Increased P50

Occurs with increased H+(decreased pH), increased PCO2​, increased temperature, and increased 2,3-DPG. This facilitates O2 release to tissues.

Left Shift (Increased Affinity, Decreased P50

Occurs with decreased H+(increased pH), decreased PCO2​​, decreased temperature, and decreased 2,3-DPG. This facilitates O2 uptake in the lung

Bohr Effect

A decrease in blood pH (due to increased CO2​ or other acids) leads to a rightward shift of the O2​-Hb dissociation curve, decreasing Hb's affinity for O2​ and promoting its release to tissues

What allows for O2s affinity to Hb lower and cause O2 to be released into the tissue?

Decreased blood pH due to increased CO2 → decreases Hbs affinity for O2 promoting its release to tissues

CO2 directly binds to Hb forming carbamino compounds

2,3-bisphosphoglycerate (2,3-DPG)

What is myoglobin and what is its affinity to O2 compared to Hb?

intracellular oxygen-binding protein found in muscle cells; acts as an oxygen reserve for muscles during periods of high demand or low blood supply.

has a much higher affinity for O2​ than hemoglobin, resulting in a rectangular hyperbolic saturation curve.

What effect describes the increased ability of deoxygenated hemoglobin to carry CO2​ compared to oxygenated hemoglobin?

The Haldane effect

What test is used to measures the levels of gases in arterial blood, providing insights into lung function and gas exchange efficiency?

Arterial blood gases (ABG) test

What does the ABG test measure?

Partial pressure of O2 and of CO2

pH

Bicarbonate

O2 content (amount of O2 in blood)

O2 saturation (percent of Hb carrying O2)

What is the main difference between Hb and myoglobin?

Myoglobin is an intracellular oxygen storage protein with one polypeptide chain, one haem group, and higher oxygen affinity than haemoglobin.

What is the normal Hb concentration?

12-17

What is the alveolar PO2 vs PO2 in the pulmonary capillary?

Alveolar: 105

Capillary: 40

What is the alveolar PCO2 vs PCO2 in the pulmonary capillary?

Alveolar: 40

Capillary: 45

What are the factors affecting gas diffusion across resp membrane?

Pressure gradient of O2 and CO2, diffusion constant of the gas, temp, surface area of membrane, thickness of membrane, ventilation-perfusion matching (VA/Q)

What is the VA/Q of lung overall, at base, and at apex?

Overall: 0.8

Base: 0.6 (perfusion decreases more significantly than ventilation towards apex)

Apex: 3.0

How does gravity affect ventilation and perfusion? (while standing)

Ventilation: basal alveoli expands more → higher ventilation at base and lower ventilation at apex

Perfusion: at apex: alveolar pressure exceeds capillary hydrostatic and venous pressure (PA>Pa>Pv)

Mid-lung: Pa>PA>Pv

Base: Pa>Pv>PA

Decreased Perfusion (QQ) with Normal Ventilation

Leads to a high VA​/Q ratio (approaching infinity). Examples include pulmonary embolism or thrombus. This results in "alveolar dead space" where ventilation is wasted

Decreased Ventilation (VAVA​) with Normal Perfusion

Leads to a low VA​/Q ratio (approaching zero). Examples include airway obstruction (e.g., asthma, pulmonary edema). This results in a "shunt" where blood passes through poorly ventilated areas without adequate oxygenation

What occurs during an airway obstruction?

• Perfusion is present, but ventilation is absent or severely reduced (VA​≈0).

• VA​/Q ratio approaches 0.

• Result: A physiological shunt. Venous blood passing through these alveoli is not oxygenated. Alveolar and arterial PO2​​ and PCO2​​ will resemble mixed venous blood. There is an increased alveolar-arterial (A−a) gradient

What occurs during pulmonary embolism?

• Ventilation is present, but perfusion is absent or severely reduced (Q≈0).

• VA/Q ratio approaches infinity.

• Result: Physiological dead space. Air entering these alveoli is not utilized for gas exchange. Alveolar PO2​​ and PCO2​​ will resemble inspired air. This ventilation is considered "wasted."

What is hypoxic vasoconstriction?

• Triggered by: Low alveolar PO2​​ in poorly ventilated areas (e.g., focal pneumonia).

• Mechanism: Pulmonary arterioles constrict in response to local hypoxia.

• Effect: Redirects blood flow away from poorly ventilated regions to better-ventilated areas, improving overall VA​/Q matching. This is opposite to systemic circulation where hypoxia causes vasodilation.

Hypocapnic Bronchoconstriction

• Trigger: High alveolar PCO2​​ or low alveolar PO2 in poorly perfused or overventilated areas.

• Mechanism: Airways constrict in response to local hypocapnia (low PCO2​​).

• Effect: Redirects airflow away from overventilated areas to better-perfused areas, improving overall VA​/Q matching.

What is the gradient that explains the difference between the partial pressure of oxygen in the alveoli (PAO2​​​) and the partial pressure of oxygen in the arterial blood (PaO2​​​)?

Alveolar-arterial (A-a) gradient

What is the value of the A-a gradient and what is its significance?

• Normal Value: Typically less than 12 mmHg.

• Significance: An enlarged A−a gradient indicates impaired gas exchange, due to diffusion defects or right-to-left shunts (VA​/Q mismatch)

How to find pulmonary vascular resistance (PVR)?

Resistance = pressure gradient / flow

What is pulmonary hypertension? What does it cause?

• Sustained elevation of mean pulmonary arterial pressure above 25 mmHg at rest or 30 mmHg during exercise.

• Causes: Constriction or stiffening of pulmonary arteries, leading to increased resistance.

• Consequences: Increased workload on the right ventricle, leading to right ventricular hypertrophy and potential heart failure.

What is the effect of VA/Q mismatch on arterial blood gases?

• Hypoventilation (Low VA​/Q): Leads to decreased arterial PO2​​ and increased arterial PCO2​​.

• Hyperventilation (High VA​/Q): Leads to increased arterial PO2​ and decreased arterial PCO2​. However, oxygen saturation may not increase proportionally with increased ventilation beyond a certain point.

• Mixing of Blood: The final arterial blood gas composition is a result of mixing blood from alveoli with different VA​/Q ratios. The CO2 dissociation curve is relatively linear, so CO2 levels are a more direct reflection of overall ventilation, while O2 levels are more complex due to the S-shaped dissociation curve and potential shunts

What curve illustrates the relationship between PO2​​ and the percentage of hemoglobin saturated with oxygen?

Oxy-hemoglobin dissociation curve

• Steep Slope: In the physiological range (e.g., 20-70 mmHg), small changes in PO2​​ cause significant changes in oxygen saturation.

• Plateau: At higher PO2​​ levels (e.g., > 80 mmHg), oxygen saturation is very high and changes little with further increases in PO2​​.

• Venous Blood: PO2​​ is around 40 mmHg, with about 75% saturation.

• Arterial Blood: PO2​​ is around 100 mmHg, with about 98-99% saturation.

What is the condition where the involuntary breathing mechanism fails?

Ondines curse

Which brain structure houses the medullary centers which are synaptically connected to pacemaker cells?

Medulla oblongata

Which brain structure contains pneumotaxic and apneustic centers that control the rate and depth of breathing?

Pons

What are the medullary centers?

• Dorsal Respiratory Group (DRG): Primarily inspiratory neurons.

• Ventral Respiratory Group (VRG): Both inspiratory and expiratory neurons (active during forced breathing).

What are the pontine centers?

• Apneustic Center: Facilitates prolonged inspiration.

• Pneumotaxic Center: Limits inspiration and facilitates expiration.

Which chemoreceptor is located in the ventral medulla?

The central chemoreceptors

They primarily respond to H+H+ in cerebrospinal fluid (CSF). They are responsible for approximately 75% of respiratory drive at rest.

Which chemoreceptor is located in the aortic bodies and carotid bodies?

The peripheral chemoreceptors

They respond to O2​, CO2​, and H+ in arterial blood, accounting for the remaining 25% of respiratory drive.

Hypercapnia

Elevated PCO2​ levels significantly stimulate ventilation.

What occurs in response to increased H+ levels in blood from metabolic acidosis stimulate ventilation to eliminate excess CO2?

Acidosis

What case of acid base regulation is this?

1. Increased H+ levels stimulate peripheral chemoreceptors.

2. Respiratory centers in the brain are triggered, increasing the rate and depth of breathing (Kussmaul's breathing).

3. This response helps to eliminate excess CO2​ and restore pH balance

Metabolic acidosis ex: diabetic ketoacidosis

In what case does the O2 uptake and CO2 production increase while the PCO2 doesn’t significantly change?

During moderate excercise

What are the factors influencing ventilation during exercise?

1. Central Command: Feed-forward signals from the cerebral cortex at the onset of exercise.

2. Sensory Feedback: Signals from muscle afferents.

3. Stress Hormones: Adrenaline release increases ventilation.

4. Hyperthermia: Increased body temperature enhances respiratory drive.

What is the Hering-Breuer reflex?

This reflex involves stretch receptors in the lungs that send signals to the brain, inhibiting further inhalation when the lungs are sufficiently inflated.

Inspiration vs expiration

Inspiration: An active process involving muscle contraction to expand the thoracic cavity and lungs.

Expiration: A passive process at rest, driven by the elastic recoil of the lungs and chest wall.

Elastic work of breathing (WOB)

Overcoming the elastic forces of the lung and chest wall. This relates to compliance, which is a measure of how easily the lungs and chest wall can expand.

• Low compliance means stiff lungs/chest wall, requiring more effort to expand.

Resistive WOB

Overcoming the resistance to airflow in the airways. This relates to airway resistance, which depends on the patency of the airways.

• High airway resistance means it's harder for air to flow through the airways.

What is compliance?

the "expandability" of the lungs and chest wall. It is defined as the change in volume per unit change in pressure

C = change in vol / change in pressure

What is airway resistance?

influenced by the total cross-sectional area of the airways. While individual small airways have a larger surface area, the total resistance is higher in larger airways due to their smaller surface area. Airway resistance is directly related to airway patency

What are the resp mechanics at resting position (end of rating expiration)

• Lungs tend to recoil inward.

• Chest wall tends to recoil outward.

• Intrapleural pressure is typically around −5 cmH2O

What are the resp mechanics at inspiration?

• Diaphragm contracts, thoracic volume increases.

• Intrapleural pressure becomes more negative (e.g., −8 cmH2O).

• Air flows into the lungs.

What are the resp mechanics at end of inspiration?

Intrapleural pressure is around −5 cmH2O

What are the resp mechanics at expiration?

• Inspiration muscles relax, elastic recoil occurs.

• Intrapleural pressure becomes less negative (e.g., −1 cmH2O).

• Air flows out of the lungs.

What are the resp mechanics at end of expiration (resting position)?

Intrapleural pressure returns to around −5 cmH2O

What occurs during low compliance and what does it lead to?

Leads to restrictive lung expansion. This is characteristic of Restrictive Lung Diseases

What occurs during high airway resistance and what does it lead to?

Obstructs airflow. This is characteristic of Obstructive Lung Diseases

What are the risk factors and the pathology of chronic obstructive pulmonary disease (COPD)?

• Risk Factors: Smoking

• Pathology: Involves:

  • Mucus hypersecretion and inflammation: Leading to narrowed airways.

  • Smooth muscle hypertrophy and fibrosis: Further narrowing the airways.

  • Destruction of alveoli (emphysema): Reduces the surface area for gas exchange and disrupts elastic recoil

What is the pathophysiology of COPD and what they lead to?

1. Air Trapping: Difficulty exhaling air due to narrowed and/or collapsed airways. This leads to:

   • Poor Ventilation: Less fresh air entering the lungs.

   • Hyperinflation: Lungs remain partially inflated even after expiration.

   • Symptoms: Dyspnea (shortness of breath), wheezes.

   • Gas exchange abnormalities: High CO2​ and low O2​ in arterial blood gases (ABGs).

2. Impaired Perfusion: Damage to pulmonary capillaries in emphysema reduces the efficiency of gas exchange between alveoli and blood. This leads to:

   • Ventilation/Perfusion (V/Q) Mismatch: Areas of the lung are ventilated but not well perfused, or vice versa.

   • Gas exchange abnormalities: Low O2​ and high CO2​ in the blood

What are the clinical findings of COPD?

• Symptoms: Dyspnea, chronic cough, sputum production, wheezes. Onset typically in middle age (40s).

• Signs:

  • Pink Puffer (Emphysema-predominant): More dyspnea, weight loss, less hypoxemic (often corrected by tachypnea), pink complexion, distant breath sounds.

  • Blue Bloater (Chronic Bronchitis-predominant): More cough and sputum, obese, hypoxemic (cyanosis), wheezes.

What are the laboratory findings in COPD?

Pulmonary Function Tests (PFTs):

• Spirometry: Essential for diagnosis.

  • FEV1​/FVC ratio: In COPD, this ratio is typically less than 70% (<0.7). Expiration takes longer, and the volume expired in the first second is reduced.

• Radiology:

  • Chest X-ray: May show hyperinflation, flattened diaphragms, and a small-sized heart.

What is interstitial lung disease (ILD)/lung fibrosis?

large group of diseases causing scarring (fibrosis) of the lungs, making them stiff and impairing gas exchange. The damage is often irreversible and progressive.

What are the causes and pathology of ILD?

• Causes: Diverse, including:

  • Environmental Exposures: Drugs, hypersensitivity pneumonitis.

  • Connective Tissue Diseases: Rheumatoid Arthritis.

  • Idiopathic: Idiopathic Pulmonary Fibrosis (IPF) has an unknown cause.

• Pathology:

  • Thickening of the alveolar-capillary membrane due to fibrosis.

  • Irregular, abnormal air spaces and scarring.

  • Reduced lung volumes.

What is the pathophysiology of ILD?

• Reduced Compliance: Inflating stiff lungs requires significantly more effort (increased Elastic WOB).

• Impaired Gas Exchange: The thickened alveolar-capillary membrane hinders the diffusion of oxygen into the blood, leading to hypoxemia.

What are the clinical and laboratory findings of ILD?

• Symptoms: Primarily dyspnea, especially on exertion. Cough may also be present.

• Pulmonary Function Tests (PFTs):

  • Reduced lung volumes: Decreased FVC and FEV1​.

  • Normal or high FEV1​/FVC ratio: Unlike obstructive diseases, the airflow rate is maintained relative to the reduced lung volume.

• Radiology:

  • Chest X-ray/CT Scan: May show reticulation (net-like pattern), nodules, and ground-glass opacities (ACF - Alveolar Consolidation/Fibrosis

What is the normal range for pH, partial pressure of O2, partial pressure of CO2, and bicarbonate?

• pH: 7.35-7.45

• Partial pressure of oxygen (pa​O2​): 10.5-13.5 kPa

• Partial pressure of carbon dioxide (paCO2): 4.5-6 kPa

• Bicarbonate (HCO3−​): 24-30 mmol/L

How to determine acidosis or alkalosis?

Low pH: acidosis

High pH: alkalosis

What does high PaCO2 mean?

respiratory acidosis (or compensation for metabolic alkalosis)