Comprehensive Study Notes

RAAS, Hypertension, and Neural Control of Blood Pressure

RAAS and Hypertension

• RAAS (Renin-Angiotensin-Aldosterone System) contributes to hypertension.
• Hypertension affects various receptors including baroreceptors and chemoreceptors.
• Drug treatment for hypertension varies:
  • Under 55 or type II diabetes: ACE inhibitors (if cough, use ARBs - Angiotensin II Receptor Blockers).
  • Over 55 or Afro-Caribbean (no diabetes): Calcium channel blockers.

Sympathetic and Parasympathetic Control

• Sympathetic nervous system: Increases heart rate (HR) and mean arterial pressure (MAP).
• Parasympathetic nervous system: Decreases HR and MAP.

Neural Control of Blood Pressure – Baroreceptor System

• Fast response system mediated by baroreceptors.
• Sensors are located in the carotid sinus, aortic sinus, and arterial walls.
• Mechanism:
  • Arterial pressure increase leads to increased vascular wall tension.
  • This activates PIEZO channels, causing an influx of Na^+ and Ca^{2+}.
  • Membrane depolarization occurs, generating action potentials.
  • Nerve endings in the carotid sinus transmit signals via the sinus nerve that joins the glossopharyngeal and vagus nerves.
  • Afferent fibers synapse in the brainstem (Nucleus of the Solitary Tract - NTS).
• Response to increased blood pressure:
  • NTS stimulates the nucleus ambiguus, leading to parasympathetic outflow via the vagus nerve to the heart (SA node).
  • This decreases HR and cardiac output (CO), reducing MAP.
• Response to decreased blood pressure:
  • NTS stimulates the vasomotor center, leading to sympathetic outflow via the reticulospinal tract to the heart.
  • This causes vasoconstriction and increased HR, increasing peripheral resistance and MAP.

RAAS, JGA, Aldosterone, and ANP

• These systems are crucial in blood pressure regulation.

Asthma and Asthma Drugs

• Beta 2 agonists are used in asthma treatment.
  • Short-acting beta agonist: Salbutamol.
  • Long-acting beta agonist: Salmeterol.

Adrenergic Receptors

• A1 (specific agonist - phenylephrine):
  • Causes smooth muscle contraction, leading to vasoconstriction and increased blood pressure.
• A2 (specific agonist - clonidine):
  • Inhibits norepinephrine release and insulin release.
• B1:
  • Increases heart rate and bronchodilation.

Review of Sympathetic Nervous System (SNS)

• Preganglionic neurons use acetylcholine (ACh).
• Postganglionic neurons typically use norepinephrine (noradrenaline), except in the PNS where ACh is used.
• SNS functions:
  • Pupil dilation
  • Inhibits salivation
  • Relaxes bronchi
  • Accelerates heart rate and increases blood pressure
  • Inhibits peristalsis and secretion
  • Activates glucose production and release
  • Secretion of adrenaline and noradrenaline
  • Inhibits bladder contraction
  • Stimulates orgasms
• Location of sympathetic ganglia:
  • Cell bodies in the lateral horn of the spinal cord: T1-L1.
  • Postganglionic neuron cell bodies in ganglia that project to target organs.
  • Pre- and postganglionic neurons synapse in paravertebral ganglia of the sympathetic chain and prevertebral ganglia.

Adrenoreceptors Effects

• Stimulatory effect:
  • Alpha 1: vasoconstriction
  • Beta 1: increase HR
• Inhibitory effect:
  • Alpha 2: (-) SNS activity
  • Beta 2: bronchodilation and vasodilation

Lung Volumes

• Tidal volume: Amount of air moved in and out of lungs during rest.
• Forced vital capacity: Maximum volume of air moved in and out of lungs in a single respiratory cycle.
• Inspiratory reserve volume: Volume of air that can be drawn into lungs after a normal inspiration.
• Expiratory reserve volume: Volume of air that can be expelled from lungs after a normal expiration.
• Residual volume: Volume of air left in lungs after maximum exhalation.
• Forced Vital Capacity = Inspiratory Reserve Volume + Tidal Volume + Expiratory Reserve Volume

Muscles of Inspiration and Expiration

Forced Inspiration

• Elevate ribs and move sternum up.
• Diaphragm: contracts, moves down.
• External intercostal muscles contract: ribcage expands (quiet breathing).
• Accessory muscles: Pectoralis minor and major, serratus anterior.

Forced Expiration

• Internal intercostals contract.
• Accessory muscles: Anterior abdominal muscles and quadratus lumborum.
• Diaphragm: relaxes, moves up.
• Ribcage: down and in.

Recoil and Compliance

• Higher recoil = less compliance.
• Compliance: Ease at which lung expands under pressure. Normally, lungs are very compliant.
• Reduced compliance:
  • Pulmonary fibrosis
  • Collapse of lung
  • Increase in pulmonary venous pressure
• Increased compliance:
  • Emphysema
  • Age

Causes of Edema

• JV(NFP)= K[(Pc – Pi) – σ(Πc- Πi)] where NFP is Net Filtration Pressure. K is filtration coefficient, Pc is Capillary Hydrostatic Pressure, Pi is Interstitial Hydrostatic Pressure σ is reflection coefficient, Πc is Capillary Oncotic Pressure, Πi is Interstitial Oncotic Pressure.
  • Increased capillary hydrostatic pressure.
  • Decreased plasma oncotic pressure.
  • Increased capillary permeability.
  • Obstruction of the lymphatic system.

Preload and Afterload

• Preload: Degree of tension/load on the ventricular muscle when it begins to contract at the end of diastole.
  • Preload index: End Diastolic Volume (EDV) - volume of blood in ventricles at the end of diastole.
  • ↑EDV leads to ↑preload, which leads to ↑active tension and ↑contraction.
  • Frank-Starling law: Changes in preload lead to changes in stroke volume.
• Afterload: Load that the heart must eject blood against.
  • ↑afterload leads to ↓ stroke volume.

Partial Pressures of Gases

• Partial pressure of a gas: In a mixture of gases, each constituent gas has a partial pressure, which is the notional pressure of that constituent gas if it alone occupied the entire volume of the original mixture at the same temperature.
• Partial pressure of oxygen: Decreases in blood and increases in alveoli, causing oxygen to flow from alveoli into blood.
• Partial pressure of CO2: Increases in blood and decreases in alveoli, causing CO_2 to flow from blood into alveoli.
• High altitude:
  • Decreased oxygen partial pressure leads to decreased partial pressure of inspired air, which leads to decreased partial pressure of alveolar air, causing decreased hemoglobin saturation in lungs and altitude sickness.

Gas Laws

• Laplace's Law: The smaller the radius of a vessel, the more pressure it can withstand (aneurysms).
• Frank-Starling Law: Force developed in a muscle depends on the extent it is stretched (changes in preload lead to changes in stroke volume).
• Boyle's Law: Pressure of a given quantity of a gas is inversely proportional to the volume that contains it (alveoli expand, pressure inside them decreases, air goes out).
• Poiseuille's Law: Small changes in the radius of a vessel (r^4) cause big changes in flow.

FEV1/FVC Ratio

• Ratio of forced expiratory volume in 1 second to forced vital capacity.
• Values above 70-80% are normal.
• In airflow limitation (i.e., asthma), the ratio drops.

ECG Intervals and Chest Leads

Chest Leads

• V1: 4th intercostal space (ICS) to the right of the sternum.
• V2: 4th ICS to the left of the sternum.
• V3: Between V2 and V4.
• V4: 5th ICS midclavicular line.
• V5: Level with V4 at the left anterior axillary line.
• V6: Level with V5 at the midaxillary line.

ECG Intervals

• P wave: Less than 0.08 sec (2 small boxes).
• P-R interval: 0.12-0.20 sec (3-5 small boxes).
• QRS complex: 0.08-0.12 sec (2-3 small boxes).
• Q-T interval: 0.35-0.43 sec – dependent on HR.

Cardiac Anatomy

• If stabbed anteriorly, most likely to hit the right ventricle since it takes up most of the anterior space of the heart.

Arteries and Veins

• Arteries: Thickest layer is the tunica media.
• Veins: Thickest layer is the tunica adventitia.

ADH (Antidiuretic Hormone)

• Blood osmolarity increases, the subfornical organ senses this and stimulates the hypothalamus (paraventricular and supraoptic nuclei).
• The posterior pituitary produces ADH.
• ADH adds additional aquaporins on the collecting duct.
• Decreases urine output volume.
• Produces more concentrated urine.
• Increases permeability of the collecting duct to urea, resulting in water reabsorption.
• Sodium reabsorption in the thick ascending loop of Henle is increased by increasing activity of NKCC, increasing the osmolarity of the medullary interstitial fluid so water is reabsorbed from collecting ducts.

Role of IL-4 in Allergies and Asthma

• Increase in IL-4 is associated with allergies and asthma.