Physio

Block 8 - Lecture 15 & 16 (Cardiac 1&2) - Chan

Cardiac 1

Describe the structure and function of the heart and the vessels
- Cardiomyocyte: striated, stimulated by AP, troponin, involuntary, intercalated discs & gap junctions
- Heart: 4 chambers, large veins (SVC & IVC → RA; pulmonary veins → LA), large arteries (RV → pulmonary arteries; LV → aorta); AV valves, semilunar valves
- Left heart = systemic circulation & right heart = pulmonary circulation
- Cardiac output (CO) = distributed among various organs via parallel arteries
  - 25% → renal, 25% → MSK, 25% → GI, 5% → coronary, 15% → cerebral, 5% → skin
- Venous return (VR): VR of L heart = VR of R heart in steady state
- Steady state: CO = VR; [CO of LV = CO of RV in a steady state; VR equal in L and R heart]
- Arterioles & venules meet @ capillaries (very high SA; single endothelial cell; site of substance exchange)
- Arterioles: blood pressure regulation
- Most of blood volume → venous system
Describe the electromechanical activity of the heart
- Em maintenance
  - Passive mechanisms:
  - Permeability K+ >> Na+ at rest (more K+ channels)
  - K+ concentration gradient
  - Non diffusible intracellular anions from negatively charged proteins
  - Active mechanisms:
  - Na+ K+ ATPase
  - Resting potential: K+ channels open, but Na+ and Ca++ closed → Hyperpolarization
  - Action potential: Na+ & Ca++ open → Depolarization; K+ open → Repolarization
Contrast pacemaker vs. non pacemaker action potentials
- Pacemaker cells: Unstable resting potentials, more negative than cardiac muscle, spontaneous depolarization/repolarization
  - SA node (60-100 BPM, Em= -55 to -60 mV, native pacemaker → overdrive suppression)
  - AV node (40-60 BPM)
  - Bundle of His (40 BPM)
  - Purkinje fibers (15-20 BPM)
- Non-pacemaker cells: Stable resting potential; prolonged depolarization sustained by Ca++ influx
Describe the ionic basis for cardiac action potential
- Non-pacemaker cells: 0 - 1 - 2 - 3 - 4
  - 0: Rapid depolarization: VG Na+ channels open, Na+ influx
  - 1: Initial repolarization: VG Na+ inactivate, K+ efflux (Kto)
  - 2: Plateau: VG Ca++ open, Ca++ influx → ventricles contract
  - 3: Repolarization: VG K+ open, K+ efflux
  - 4: Rest: outward K+ current
- Pacemaker cells: 4 - 0 - 3 - 4
  - 4: Diastolic/spontaneous depolarization: cation influx (Na+ via funny channels)
  - 0: Slow depolarization: VG Ca++ channels, Ca++ influx
  - 3: Repolarization: K+ efflux → Maximum diastolic potential (-65 mV)
Describe the dual innervation to the cardiac system involving the ANS
- SANS: NE → + B1 adrenergic R (Gs/GPCR)→ increase cAMP
  - Increase in cAMP:
  - Increase HCN → increased Na+ influx & rate of phase 4 depolarization
  - Increase phosphorylation of Ca+ channel, Ca++ influx → moves threshold toward Vm
  - OVERALL: Increased HR, increased rate of conduction through AV node
- PANS: ACh → +M2 receptors (Gi/GPCR) → decrease cAMP →
  - ACh → increase muscarinic K+ channel efflux → negative shift in Vm
  - Decrease in cAMP leads to:
  - decrease HCN → decrease Na+ influx & rate of phase 4 depolarization
  - decrease Ca+ channel phosphorylation → less Ca+ → AP threshold moves away from Vm
  - RESULT: decreased HR, decreased rate of conduction through AV node
Describe pathology that affects pacemaker function and potential

	Increase HR	Decrease HR
Drugs	Beta adrenergic agonists	Beta adrenergic antagonists
		Digoxin
Hormones	Hyperthyroidism (High T3, T4)	Hypothyroidism (Low T3, T4)
	Catecholamines (epinephrine)
Ions	Hypokalemia (hyperpolarizes cell)	Hyperkalemia

**Anti-arrhythmic drugs: can block Na+, K+, or Ca++ channels

Heart too slow → atropine
Heart too fast (SVT) → adenosine
Beta blockers also decrease heart rate

**Hyperkalemia: high extracellular K+ depolarizes the cell & decreases the full activation of If 7. Describe the propagation and spread of heart cell depolarization

Ca++ triggers contraction → intercalated discs/connexons (propagated throughout cardiac muscle because of syncytial organization)
Excitation-contraction coupling in cardiac muscle: Calcium mediated calcium release (Ca++ enters via L type VG Ca++ channels → triggers release of Ca++ from SR → muscle contraction)
- Increase [Ca++]i → contracted sarcomere
- Decrease [Ca++]i → relaxed sarcomere

Describe the cardiac electrophysiology involved in varied cardiac rhythm involved in pathology
- Death of pacemaker → bradyarrhythmia (blood pressure can not be maintained); can lead to sudden death
- Tachyarrhythmia - blood pressure can not be maintained → syncope, sudden death
  - V fib
  - V tach
  - Torsades de pointes

Cardiac 2

Explain the function of gap junctions
- Electrical activity (movement of ions & current flow) in cardiac cells transmitted to neighboring cells via intercalated disks
  - Intercalated disks contain:
- Gap junctions (low resistance connections found between cells)
- Connexins (channels formed by proteins in gap junctions)
- Desmosomes (firm mechanical attachments)
Discuss the different phases of non pacemaker action potentials
- Non-pacemaker cells: Stable resting potential; prolonged depolarization sustained by Ca++ influx
  - Phases: 0-1-2-3-4 0: Rapid depolarization: VG Na+ channels open, Na+ influx 1: Initial repolarization: VG Na+ inactivate, K+ efflux (Kto) 2: Plateau: VG Ca++ open, Ca++ influx → ventricles contract 3: Repolarization: VG K+ open, K+ efflux 4: Rest: outward K+ current
Describe and list the components in the myocyte conduction pathway
- SA node → AV node (via internodal pathway) + left atrium (via interatrial tract/Bachman’s bundle → Bundle of His → Left and right bundle branches → Purkinje fibers

1. SA node 2. Atria 3. AV node 4. Bundle of His 5. Purkinje system 6. Ventricles

Physiologic basis for conduction: local currents & gap junctions

Conduction through the atria * Ends of SA node fibers → directly connect w/ surrounding atrial muscle fibers * Velocity ~ 0.3 m/s [some fibers as fast as 1 m/s & more similar to Purkinje fibers] * Faster fibers located in internodal pathways & interatrial band to left atrium

Conduction through the AV node * Slowed conduction allows for ventricular filling & coronary circulation * Occurs due to decreasing # of gap junctions between successive fibers * Increases resistance to flow of ions

AV delay

1. Impulse arrives 0.03 s after origin in SA node 2. 0.09 s in AV node before impulse → Bundle of His (running total 0.12 s) 3. Another 0.04 s delay in Bundle of His (0.16 s)

Conduction through Bundle of His * Delay of 0.04 seconds * AV bundle: only tissue continuous between atria and ventricles (everywhere else surrounded by fibrous tissue) * Atrioventricular fibrous tissue = barrier between atria & ventricles; acts as insulator (prevents passage of impulse between them except through AV bundle)

Conduction through ventricles * Gap junctions → rapid conduction * Purkinje system → most rapid conduction @ 1.5 - 4 m/sec * Once impulse reaches the end of the Purkinje fibers → thru ventricular muscle mass via muscle fibers (slows down 0.3 - 0.5 m/s) * Slowest: AV node to allow for ventricular filling * Fastest: Purkinje fibers (gap junctions, ventricular muscle contracts as syncytium)

Discuss different types of blocks in the myocyte pathway
- Heart rate = electrical & mechanical component
  - Electrical component: regulates timing of mechanical component
  - Ex. excitation-contraction coupling
- Cardiac arrhythmias → defects in electrical component (timing)
- Heart failure → defects in mechanical component (pump not functioning)
- Cardiac arrhythmias are caused by altered impulse formation, altered impulse conduction, or both altered impulse conduction/formation
  - 3 types
  - Re-entry or Circus movements
  - Conduction block
    - Caused by ischemia/scarred/refractory tissue (disease) which blocks SA nodal impulse conduction
    - Latent pacemakers take over → bradycardia
    - Symptomatic bradycardia tx w/ atropine → block effects of ACh on nodal tissue @ M2 receptors
  - Accessory pathways

*AV nodal blocks: most clinically significant heart block (conduction block can also occur @ Bundle of His or at left or right bundle branches)

1st degree AV block
- Delayed conduction through AV node
- Still has sinus rhythm

2nd degree AV block * Some atrial AP do not conduct into ventricles (dropped beat) * May be 2-3 depolarizations/ventricular depolarization * Results in ventricular bradycardia (not all AP reaching ventricles); tx: antiarrhythmics

3rd degree AV block * Most severe; impulses not reaching the ventricles → complete dissociated between atrial (P waves) and ventricular (QRS) depolarizations/contractions * Latent pacemakers take over (Purkinje fibers: rate 30 BPM) ⇒ ventricular bradycardia

Explain different types of abnormal conduction caused by ectopic foci
- Ectopic foci = when other cells become pacemakers
  - Purkinje can take over ⇒ much slower
  - Diseased areas can become ectopic foci & if they fire at a faster rate → overcome SA node ⇒ rapid abnormal heart rate
- On ECG → Wide QRS + PVCs (premature ventricular complexes)

%%Block 9: Cardiac 3 - Riskin%%

Explain the function of an electrocardiogram (ECG)
- Taking a picture of the hearts electrical activity; wave of positive charge
Describe the sequence of ventricular depolarization

Starting point: SA node → primary pacemaker Depolarization wave occurs → P wave
Have a slight delay in the AV node
Start of the QRS complex Starts with a small downward deflection Depolarization of the septum of the heart from L → R (small negative reflection → Q) Negative deflection → small positive force traveling towards negative pole
Depolarization towards the apex of the heart (positive deflection → R) Have large vector traveling towards the positive pole
Depolarization of LV→ towards baseline (S) Once completely depolarized → back to baseline levels
1. Discuss the different wave tracings on an ECG graph
-P wave: atrial depolarization (0.08 - 0.10 s) → top part of heart depolarizing
PR interval: allow ventricular filling involving AV nodal delay, bundle of His and branches (0.12 - 0.20s) → from start of P wave to the start of the QRS complex
QRS: ventricular depolarization (between 0.06 - 0.10 s) → pushing blood from the bottom part of the heart throughout the body
QTc interval = QT/sq. root RR → ventricular AP; (≤ 0.44 s) → from start of QRS complex to the end of the T-wave
ST segment: interval between ventricular depolarization and repolarization→ from the end of the S wave to the start of the T wave
T wave: ventricular repolarization
U wave: bump after T wave but only used in pathological findings
1. Learn how to read an ECG tracing (intervals and their significance)
See notability notes & practice problems
1. List the different ECG leads, know their locations on the body and their functions
Limb leads: RA, RL, LA, LL → bipolar limb leads: I, II, III & unipolar augmented leads: aVR, aVL, aVF
- Lead 1: RA → LA
- Lead II: RA → LF
- Lead III: LA → LF
- Augmented leads: go fro center to RA, LA, or LF (negative center towards positive arm/leg lead)
Precordial leads: V1-V6 (unipolar)
1. Contrast a normal and abnormal ECG axis
Normal axis: -30 to +90 degrees
- I, II, III: positive w/ R wave in I > III
Right axis deviation: +90 to +180 degrees
- Lead I always negative, Lead III always positive (lead II can be +/-)
Left axis deviation: -30 to -90 degrees
- Lead I always positive, Lead III always negative
1. Recognize different ECG abnormalities
AV block
- 1st degree: Prolonged PR interval 0.21 s +
- 2nd degree
  - Mobitz Type I: Progressive PR + dropped beats
  - Mobitz Type II: Fixed PR + dropped beats
- 3rd degree: P > QRS, dropped beats, no relation between P and QRS
Lacking P waves
- Atrial fibrillation: decreased amplitude, increased frequency - atrial fibrillatory waves
- Atrial flutter: sawtooth pattern, irregularly irregular - coarse fibrillatory waves
- Sinus arrest w/ escape rhythm: retrograde atrial stimulation, bradycardia, no P wave, small QRS, and P & WRS are synchronized
Ventricular problems
- PVCs
- V-tach
- V-fib
STEMI
- ST segment appears elevated, but the baseline is actually shifted higher due to ischemia
- ST segment correlates to phase 3 of the AP; entire myocardium at 0 mV & energy current disappears
- ST elevation → transmural infarct involving the entire wall thickness of a ventricular region
- ischemic tissue becomes depolarized because of its inability to maintain normal ion gradients across the cell membranes
  - When the noninvolved myocardium is repolarized (between the end of the T wave and beginning of the QRS), there exists injury currents created by the separation of depolarized injured tissue and polarized normal tissue.
  - electrode overlying the ischemic tissue → negative voltages because the electrical vector will be in a direction away from the electrode. Therefore, at a time when the entire ventricle should be repolarized and when the ECG baseline voltage should be 0, the electrode instead records a negative voltage
  - When the entire ventricle is depolarized with the appearance of the QRS, then the voltage difference between the ischemic & normal tissue disappears and the electrode records an isoelectric ST segment. However, this segment will appear elevated compared with the depressed baseline
    - ECG changes (e.g., formation of prominent Q waves) occur over the hours and weeks following a STEMI
    - https://journals.physiology.org/doi/full/10.1152/advan.00105.2016
MEA
- The mean electrical axis moves away from areas of ischemia but towards areas of hypertrophy

Block 10: Cardiac 4 & 5 - Parmar

Cardiac 4

Contrast systole vs. diastole
- diastole: relaxation and filling
  - isovolumetric relaxation (SL closed and atria fill) ventricular pressure drops below atrial pressure → AV valves open → blood flow from atria to ventricles → atrial systole forces more blood into the ventricles at the end of v. diastole
  - longer than systole
- systole: contraction and ejection
  - ventricles contract → ventricular pressure > atrial pressure → AV valve closure S1 → isovolumetric contraction → ventricular pressure > aortic BP → aortic valve opens and blood ejected
  - ventricles contract to PA and Aorta; AV valves closed
Discuss the different steps of the cardiac cycle and understand what is happening at each step (polarizations, valves, open/close, volumes)

Calculate ventricular EF & understand its importance
- EF = (EDV - ESV)/EDV → SV/EDV
- Normal: 55-60%
- Heart failure EF < 50%, may be as low as 15%
Discuss the different steps of the cardiac cycle on the graph and be able to label important points (chamber filling/emptying, valve open/close, heart sounds)

Understand how to interpret the pressure volume loop (chamber filling, valve open/close, heart sounds)

Cardiac 5

Calculate cardiac output and understand its importance
Calculate stroke volume and understand its importance
Define preload and understand the factors that determine preload
Determine Frank Starling Law
Explain how preload effects PV loops
Define afterload and understand the factors that determine afterload
Explain how afterload effects ventricular function
Explain how afterload effects PV loops
Explain the regulation of inotropy and its effects on ventricular function

Block 11. Respiratory 1 & 2 - Panvelil

Poiseuille's law \n
Alveolar ventilation calculation \n
Airway resistance \n
CO2 & ventilation \n
Surfactant specifics \n
Pneumocyte types \n
Pulmonary circulation details \n
Resistance pressure relation \n
Distention & recruitment \n
1. High & Low lung volumes \n
2. Specifics on 3 zones of lungs

B12. Respiratory 3 & 4 - Riskin

Respiratory 3

Gas transport & its function
- Dissolved oxygen is not survivable, O2 has low solubility
  - must bind to O2
- Function: carry O2 hgb throughout body and get rid of waste
Physical and graphical relation between hgb and O2 binding
- O2 binding → more O2 binding
- Two Y axises
  - % Hb saturation
  - O2 concentration (ml/100 ml)
- X axis: Partial pressure of O2
Contrast the cases behind a left shift vs a right shift on the O2-hgb saturation graph
- P50 = PO2 sat 50% Hgb saturation → indicates affinity of O2 for Hgb

Left shift: increased O2 affinity → decreased O2 offloading (R state)
Right shift: decreased O2 affinity → increased O2 offloading (T state) {greater tissue effect}

R state = fully O2 hgb while T state = deoxy hgb

Interpret partial pressures & how they affect saturation
- Partial pressures: the higher the P02, the higher the percentage O2 saturation of hgb
- Arterial: PaO2 95 mmHg → PaCO2 40 mmHg
- ALVEOLAR: PAO2 100 mmHg → PACO2 40 mmHg
- Venous: PvO2 40 mmHg → PvCO2 46 mmHg
- Partial pressures need to different in arterial vs. venous blood to pick up/drop off O2/CO2
Explain how CO2 is transported through the body
- 5% dissolved, 5% hgb, and 90% via HCO3-
- RBCs have CA which convert CO2 → HCO3-

Respiratory 4

Calculate A-a gradients using the alveolar gas equation
Recognize causes of tissue hypoxia and the body’s compensatory mechanisms
Explain diffusional impairment and discuss clinical conditions associated & shunting (compensatory mechanisms)
Discuss ventilation to perfusion inequality and the different zones it causes in the lungs
Describe the change in compliance in the different regions of a lung when it is upright and how that affects the ventilation/perfusion ratio
Identify the common causes of hypercapnia

==Block 13 - Respiratory 5 - Benmerzouga==

State what can be controlled in respiration
- Rate and depth can both be controlled consciously (voluntary control - cerebrum)
- Many receptors → respiratory control centers in medulla and pons → spinal motor neurons → intercostals and accessory muscles + diaphragm
List the different sensors/receptors in the body used to regulate breathing and their effectors
- Chemoreceptors → rate and depth
  - Central: H+ [H+ cannot cross BBB, CO2 can and CA in CSF → H+]
  - Peripheral: CO2, O2, H+
  - Carotid → CN IX glossopharyngeal nerve → ! only responds to PaO2 and not [O2]
  - Aortic → CN X
- Mechanoreceptors
  - Lung receptors
  - Stretch: fire w/ inspiration → inspiratory off switch
    - Hering-Breur reflex protects lungs from over inflation
    - **slow adapting receptors
  - J receptors: increased pulmonary interstitial volume activates R → induce rapid shallow breathing
  - Irritant: responds to noxious irritants → coughing, gasping, breath holding
    - Stimulated by: histamine, serotonin, prostaglandins
    - **rapid adapting receptors
  - Muscle proprioceptors: located in tendons and muscle spindles; if both are activated → increase RR
  - Play important role in exercise
Locate the respiratory control centers and explain their important functions
- Medulla = primary respiratory control
  - Also contains centers for swallowing and vomiting
  - Two regions in medulla
  - DRG: constant breathing rhythm, normal inspiration (normal expiration is passive)
  - VRG: forced inspiration and forced expiration
- Pons = pontine respiratory group
  - Apneustic centers: neurons that stimulate DRG → deep breathing (depth and rate of inspiration; expiration is passive)
  - Pneumotaxic centers: inhibit DRG → increase RR (by limiting the inspiratory period)
Compare and contrast the central and peripheral chemoreceptors
- Central: PaCO2 → medulla oblongata: CO2 crosses BBB → CSF w/ CA
- Peripheral: monitors pH, PCO2, PO2
  - Most critical in response to hypoxia
  - Little response to normoxia
  - Metabolic acidosis → pH monitoring → ventilatory compensation
Recognize the interrelations of blood gasses on ventilation
- PO2 must be reduced < 60 mmHg to significantly increase ventilation (sharp, curved line)
  - Hypoxic induced ventilatory response is mediated by the peripheral chemoreceptors
- PC02: + 5 mmHg change → +/- 50% ventilation
  - alveolar CO2 is a powerful stimulus of ventilation
- Minute ventilation is inversely related to alveolar PO2; directly related to PCO2 and arterial H+ ions
Recognize the other sensors with pulmonary implications