Sequencial events of a cardiac cycle including concurrent pressure volume change and generation of heart sound

Reading File

Finding Sources

Searching Images

cardiac cycle pressure volume changes heart sounds Wiggers diagram

Reading File

Finding Sources

Loading Image

Reading File

Loading Image

Reading File

I now have all the information needed for a comprehensive, well-sourced answer. Let me compose the full response.

The Cardiac Cycle: Sequential Events, Pressure-Volume Changes, and Heart Sounds

The cardiac cycle spans from the beginning of one heartbeat to the beginning of the next. At a heart rate of 72 beats/min, the total duration is approximately 0.83 seconds (systole ~0.3 s, diastole ~0.5 s). The cycle is initiated by spontaneous depolarization of the sinoatrial (SA) node, which triggers atrial then ventricular contraction after a 0.1 s AV nodal delay.

The diagram below (from Costanzo Physiology) is the definitive Wiggers-style reference - study each phase (A through G) against pressure, volume, venous pulse, and heart sounds simultaneously:

Cardiac Cycle - Wiggers Diagram showing all 7 phases with pressures, volumes, venous pulse, ECG, and heart sounds

The Seven Sequential Phases

Phase A - Atrial Systole

Parameter	Event
ECG	P wave (atrial depolarization) followed by PR interval
Valves	Mitral (AV) valve already open; aortic valve closed
Pressure	Left atrial pressure rises; small "blip" in LV pressure as blood is actively added
Volume	LV volume increases (final ~20-30% of ventricular filling)
Heart Sound	S4 (fourth heart sound) - not audible in normal adults; heard when ventricular compliance is decreased (e.g., LV hypertrophy)

The atria act as primer pumps: atrial contraction produces the "a wave" on the venous (JVP) pulse. The ventricle was already filling passively before this phase - atrial systole contributes roughly the last 20% of end-diastolic volume (EDV). The EDV at end of this phase is approximately 120 mL.

Phase B - Isovolumetric Ventricular Contraction (IVC)

Parameter	Event
ECG	QRS complex (ventricular depolarization)
Valves	Mitral valve closes (when LV pressure exceeds LA pressure); aortic valve still closed
Pressure	LV pressure rises steeply from ~10 mmHg toward ~80 mmHg; all other pressures relatively unchanged
Volume	Constant at ~120 mL (EDV) - both AV and semilunar valves are closed
Heart Sound	S1 ("lub") - caused by vibration of the taut mitral (and tricuspid) valve leaflets at closure, plus reverberation of blood and ventricular walls

This is the most energy-expensive phase per unit time. The ventricle builds up pressure without shortening. S1 is split because the mitral valve closes slightly before the tricuspid valve. The "c wave" appears on the venous pulse, caused by bulging of the tricuspid valve into the right atrium.

Phase C - Rapid Ventricular Ejection

Parameter	Event
ECG	ST segment (ventricular depolarization complete, repolarization not yet started)
Valves	Aortic valve opens (when LV pressure exceeds aortic diastolic pressure ~80 mmHg)
Pressure	LV pressure rises to its peak (~120 mmHg); aortic pressure rises to its maximum (~120 mmHg)
Volume	LV volume drops rapidly; most of the stroke volume (~70%) is ejected in this phase
Heart Sound	None

Blood is driven from the LV into the aorta by a LV-to-aorta pressure gradient. Left atrial pressure begins to rise as blood returns from the lungs (filling for the next cycle). The venous "x descent" (tricuspid annulus pulled down) occurs here.

Phase D - Reduced Ventricular Ejection

Parameter	Event
ECG	T wave (ventricular repolarization begins)
Valves	Aortic valve still open; mitral still closed
Pressure	LV pressure starts to fall (ventricle beginning to relax); aortic pressure also starts to fall as runoff into arteries exceeds inflow from ventricle
Volume	LV volume continues to decrease, but at a slower rate, reaching the end-systolic volume (ESV) ~50 mL
Heart Sound	None

By the end of phase D, stroke volume = EDV - ESV = 120 - 50 = 70 mL. Ejection fraction = 70/120 = ~58%.

Phase E - Isovolumetric Ventricular Relaxation (IVR)

Parameter	Event
ECG	After end of T wave (full repolarization)
Valves	Aortic valve closes (when LV pressure falls below aortic pressure); mitral valve still closed
Pressure	LV pressure falls steeply from ~100 mmHg to near zero; aortic pressure shows the dicrotic notch (incisura) at the point of aortic valve closure
Volume	Constant at ~50 mL (ESV) - all valves closed
Heart Sound	S2 ("dub") - caused by sudden closure and elastic recoil of the semilunar valves (aortic then pulmonary), producing blood reverberation in the aortic/pulmonary roots

S2 is shorter (0.11 s) and higher pitched than S1 (0.14 s) because the semilunar valves are tauter than AV valves. Physiological splitting of S2 on inspiration: inspiration delays pulmonic valve closure (increased RV filling via Frank-Starling mechanism prolongs RV ejection), widening the A2-P2 interval. The venous "v wave" (atrial filling against closed tricuspid valve) peaks here.

Phase F - Rapid Ventricular Filling

Parameter	Event
ECG	Isoelectric baseline
Valves	Mitral valve opens (when LV pressure falls below LA pressure)
Pressure	LV pressure low but constant (compliant relaxed ventricle); aortic pressure continues to fall as blood runs off to periphery
Volume	LV volume increases rapidly from ~50 mL to ~100 mL
Heart Sound	S3 (third heart sound) - caused by oscillation of blood reverberating between ventricular walls as blood rushes in from the atrium

S3 is normal in children and young adults but in adults over ~40 it indicates volume overload (e.g., systolic heart failure, mitral/tricuspid regurgitation). The venous "y descent" occurs as the tricuspid valve opens. The atria had been filling throughout systole (phases B-E), so they are now full and empty rapidly into the ventricle.

Phase G - Reduced Ventricular Filling (Diastasis)

Parameter	Event
ECG	Isoelectric baseline; cycle ends with next P wave
Valves	Mitral valve still open
Pressure	LV and LA pressures equalize at low values
Volume	LV volume increases gradually from ~100 to ~120 mL
Heart Sound	None (silence until next P wave triggers atrial systole)

This is the quiet period where pressure and volume equilibrate across the open mitral valve. At faster heart rates, this phase is the first to be shortened or abolished.

Summary Table: All Phases at a Glance

Phase	ECG Event	Valves	LV Pressure	LV Volume	Heart Sound
A - Atrial Systole	P wave	MV open, AoV closed	Slight rise	↑ to EDV (120 mL)	S4 (pathological)
B - IVC	QRS	MV closes	↑↑ (10→80 mmHg)	Constant (120 mL)	S1
C - Rapid Ejection	ST segment	AoV opens	↑ to max (~120 mmHg)	↓↓ rapidly	None
D - Reduced Ejection	T wave	AoV open	↓ slightly	↓ to ESV (50 mL)	None
E - IVR	Post-T	AoV closes	↓↓ (100→7 mmHg)	Constant (50 mL)	S2 + dicrotic notch
F - Rapid Filling	Isoelectric	MV opens	Low, constant	↑↑ rapidly	S3 (normal in young)
G - Diastasis	Pre-P	MV open	Equalized, low	↑ slowly to ~120 mL	None

Pressure-Volume Loop

The P-V loop plots LV pressure (y-axis) against LV volume (x-axis), traversing counterclockwise. It captures all four phases geometrically:

Segment	Phase	Description
A → B	Early rapid filling	Mitral valve opens; volume rises 50→70 mL, pressure slightly falls (ventricle still relaxing)
B → C	Late filling (diastasis + atrial systole)	Volume rises 70→120 mL (EDV) with modest pressure rise (high compliance)
C → D	Isovolumetric contraction	Vertical line at 120 mL; pressure rises 10→80 mmHg (mitral closed, aortic closed)
D → E	Ventricular ejection (rapid + reduced)	Aortic valve open; volume falls 120→50 mL; pressure peaks at ~130 mmHg then falls
F → A	Isovolumetric relaxation	Vertical line at 50 mL; pressure falls 100→7 mmHg (both valves closed)

The area enclosed within the loop = net stroke work done by the LV per beat. The width of the loop at any level = stroke volume (70 mL at baseline).

Heart Sounds: Mechanism Summary

Sound	Timing	Cause	Clinical Note
S1 ("lub")	Start of systole (IVC)	Mitral (mainly) + tricuspid valve closure; vibration of taut leaflets, chordae, blood, and ventricular wall	Duration ~0.14 s; split = M1 before T1
S2 ("dub")	End of systole (IVR)	Aortic + pulmonary valve closure; elastic recoil of semilunar leaflets; blood reverberates in aortic root	Duration ~0.11 s; higher pitch than S1; physiological splitting on inspiration (A2-P2)
S3	Early diastole (rapid filling)	Blood oscillating between ventricular walls during rapid inflow; low frequency	Normal in children/<40 yrs; in adults = volume overload/systolic HF
S4	Late diastole (atrial systole)	Atrium contracting against stiff/hypertrophied ventricle; very low frequency	Always pathological in adults; = decreased ventricular compliance

Key Numbers to Remember (at 72 beats/min)

Total cycle duration: 0.83 s
Systole (B-E): ~0.3 s; Diastole (F-A): ~0.5 s
EDV: ~120 mL | ESV: ~50 mL | Stroke volume: ~70 mL | EF: ~58%
Peak LV systolic pressure: ~120 mmHg | Aortic diastolic pressure: ~80 mmHg
Duration S1: ~0.14 s | Duration S2: ~0.11 s

Sources: Costanzo Physiology 7th Edition, pp. 160-162; Guyton and Hall Textbook of Medical Physiology, Chapters 9 & 23; Medical Physiology (Boron & Boulpaep), p. 761-762

Basal ganglion function connection and parkinson

Finding Sources

Searching Images

basal ganglia direct indirect pathway dopamine Parkinson disease circuit diagram

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

Loading Image

Reading File

I now have all the material needed for a comprehensive, well-illustrated answer. Let me compose the full response.

Basal Ganglia: Function, Connections, and Parkinson's Disease

1. Components and Anatomy

The basal ganglia are a collection of subcortical gray matter nuclei deep within the cerebral hemispheres. The main components are:

Structure	Division	Role
Caudate nucleus	Input (striatum)	Receives cortical input; cognitive/limbic loops
Putamen	Input (striatum)	Receives cortical input; motor loop
Caudate + Putamen = Striatum (neostriatum)	Major input nucleus	All BG inputs arrive here
Globus Pallidus externa (GPe)	Intrinsic/relay	Intermediate relay in indirect pathway
Globus Pallidus interna (GPi)	Output	Major inhibitory output to thalamus
Subthalamic Nucleus (STN)	Intrinsic	Excitatory relay in indirect pathway
Substantia Nigra pars compacta (SNc)	Modulatory input	Dopaminergic; projects to striatum
Substantia Nigra pars reticulata (SNr)	Output	Acts in parallel with GPi; output to thalamus

The striatum receives virtually all inputs. The GPi and SNr are the two major output nuclei. Their output is tonically inhibitory (GABAergic) to the thalamus - this is the fundamental principle on which the entire circuitry rests.

2. Functions of the Basal Ganglia

The basal ganglia do not directly activate muscles or project to the spinal cord. Their role is modulatory:

Motor control - facilitation and inhibition of voluntary movements; initiation, execution, and termination of learned motor tasks
Action selection - selecting one motor program while suppressing competing ones ("go/stop" gating)
Motor learning and habit formation - procedural memory (how to ride a bike)
Cognitive functions - working memory, attention, planning (via prefrontal loops)
Limbic/affective functions - motivation, reward processing (via nucleus accumbens/ventral striatum)
Oculomotor control - via the superior colliculus (SNr projections)

3. The Cortico-Basal Ganglia-Thalamo-Cortical Loop

All information flows in reentrant closed loops: Cortex → Striatum → Output nuclei → Thalamus → Cortex (back to the same cortical area that initiated the signal). There are at least five parallel loops:

Loop	Cortical Origin	Striatal Region	Function
Motor	Motor/premotor cortex	Putamen	Voluntary limb movement
Oculomotor	Frontal eye fields	Caudate (body)	Saccadic eye movements
Prefrontal	Dorsolateral PFC	Caudate (head)	Spatial working memory
Orbitofrontal	Orbital/medial PFC	Caudate (ventromedial)	Motivation, social behavior
Limbic	Anterior cingulate, hippocampus	Nucleus accumbens/ventral striatum	Emotion, reward

4. The Direct and Indirect Pathways

This is the central circuit model. The diagram below (from Stahl's Essential Psychopharmacology) shows the complete "go" (direct) and "stop" (indirect) pathways with their neurotransmitters:

Basal Ganglia Direct (Go) and Indirect (Stop) Pathways - showing D1/D2 receptor populations, GABA and glutamate synapses, and dopamine modulation from SNc

Direct Pathway ("Go" - Movement Facilitating)

Cortex →(+Glu)→ Striatum (D1 neurons) →(-GABA)→ GPi/SNr →(-GABA)→ Thalamus →(+Glu)→ Cortex

Step-by-step logic:

Cortex excites striatal D1 neurons (+)
Striatal D1 neurons inhibit GPi/SNr (-)
GPi/SNr are now less active, so they release their inhibition of the thalamus (double negative = positive)
Thalamus is now free to excite the motor cortex (+)
Net effect: Movement is facilitated ("GO")

Neurotransmitters in direct pathway: striatal neurons contain GABA + Substance P

Indirect Pathway ("Stop" - Movement Inhibiting)

Cortex →(+Glu)→ Striatum (D2 neurons) →(-GABA)→ GPe →(-GABA)→ STN →(+Glu)→ GPi/SNr →(-GABA)→ Thalamus →(+Glu)→ Cortex

Step-by-step logic:

Cortex excites striatal D2 neurons (+)
Striatal D2 neurons inhibit GPe (-)
GPe, now less active, releases its inhibition of STN (double negative = +)
STN is disinhibited and actively excites GPi/SNr with glutamate (+)
GPi/SNr are overactive and strongly inhibit the thalamus (-)
Thalamus is suppressed, so less excitation reaches the cortex
Net effect: Movement is suppressed ("STOP")

Neurotransmitters in indirect pathway: striatal neurons contain GABA + Enkephalin

Memory Trick

"Indirect Inhibits" - the indirect pathway inhibits movement; the direct pathway facilitates it. Their outputs are balanced and opposite.

5. Dopamine Modulation: The Master Regulator

Dopamine from SNc projects to the striatum (the nigrostriatal pathway) and acts on two populations of receptors with opposite effects:

Receptor	Pathway	Effect of DA	Net Effect
D1	Direct	Excites D1 neurons → activates direct pathway	↑ Movement (Go)
D2	Indirect	Inhibits D2 neurons → dampens indirect pathway	↓ Stop signal (also = Go)

Both D1 activation and D2 inhibition push in the same direction - toward movement facilitation. This is why dopamine = "pro-movement." Loss of dopamine from either mechanism tips the balance toward the stop signal.

6. Parkinson's Disease: The Circuit Fails

Pathology

In Parkinson's disease, dopaminergic neurons of the SNc degenerate progressively. By the time motor symptoms appear, approximately 60-80% of SNc neurons are already lost (and 80% of striatal dopamine is depleted). The degenerating neurons accumulate Lewy bodies (alpha-synuclein aggregates).

The diagram below (from Harrison's Principles of Internal Medicine, 22nd edition) contrasts the circuit in the normal state (A), PD (B), and levodopa-induced dyskinesia (C):

Harrison's Basal Ganglia Circuit in Normal vs Parkinson's Disease vs Dyskinesia showing changes in GPi/STN activity

What Goes Wrong in the Circuit

Without dopamine:

Pathway	Change	Consequence
Direct	Loss of D1 stimulation → striatum less active → GPi/SNr more active → thalamus more suppressed	Less "GO" signal
Indirect	Loss of D2 inhibition → striatum more active → GPe more inhibited → STN disinhibited → GPi/SNr more active (from two sources now) → thalamus even more suppressed	"STOP" signal dominates

Bottom line: GPi/SNr become overactive, excessively inhibiting the thalamus, which then fails to excite the motor cortex adequately → hypokinesia/bradykinesia.

Additionally, the dopamine-ACh balance in the striatum is disrupted: dopamine normally inhibits ACh interneurons. Loss of dopamine leads to relative cholinergic excess in the striatum, contributing to tremor and rigidity. This is why anticholinergic drugs provide partial symptomatic relief.

Clinical Features (TRAP)

Feature	Mechanism
Tremor (resting, 4-6 Hz, "pill-rolling")	Oscillations in basal ganglia-thalamo-cortical loop without adequate dopamine dampening
Rigidity (cogwheel/leadpipe)	Increased tonic contraction; loss of BG-mediated reciprocal inhibition
Akinesia/Bradykinesia	Failure of direct pathway "GO" signal; inability to initiate/scale movement
Postural instability	Loss of postural righting reflexes; cholinergic pedunculopontine nucleus (PPN) degeneration

Other features from non-dopaminergic neurodegeneration (per Braak staging):

Micrographia (small handwriting)
Hypophonia (soft voice), dysphagia
Anosmia (early - olfactory bulb affected first)
REM sleep behavior disorder (RBD - often precedes motor symptoms)
Autonomic dysfunction: orthostatic hypotension, constipation
Cognitive impairment / PD dementia (late stages)

7. Braak Staging of PD Pathology

Lewy body pathology spreads in a predictable pattern (ascending):

Stage	Regions Affected	Clinical Correlate
1-2	Olfactory bulb, dorsal motor nucleus of vagus	Anosmia, constipation, RBD (prodromal)
3-4	SNc, basal forebrain, amygdala	Motor symptoms emerge (Stage 3)
5-6	Neocortex (temporal, prefrontal)	Cognitive impairment, dementia

8. Treatment Strategies (Targeting the Circuit)

Treatment	Mechanism	Target
Levodopa (L-DOPA)	Dopamine precursor; crosses BBB, converted to DA	Restores D1/D2 signaling
Dopamine agonists (pramipexole, ropinirole)	Directly stimulate D2 (and D3) receptors	Bypass depleted SNc
MAO-B inhibitors (selegiline, rasagiline)	Reduce DA breakdown in striatum	Prolong synaptic DA
COMT inhibitors (entacapone)	Reduce peripheral L-DOPA breakdown	Extend L-DOPA effect
Anticholinergics (benztropine)	Reduce relative cholinergic excess	Address ACh-DA imbalance
Deep Brain Stimulation (DBS) of STN or GPi	High-frequency stimulation effectively inhibits overactive STN/GPi	Restores thalamic output
Levodopa-induced dyskinesia	Chronic D2 stimulation → hypersensitivity → GPi/STN underactive → thalamus over-excited	Diagram C above

Summary: The Core Logic

NORMAL:     SNc-DA     → D1 activates direct ("GO") + D2 inhibits indirect ("STOP")
                       → Balanced thalamic output → normal movement

PARKINSON:  SNc-DA ↓↓  → Direct pathway WEAK + Indirect pathway OVERACTIVE
                       → GPi/SNr OVERACTIVE → Thalamus SUPPRESSED
                       → Motor cortex UNDER-ACTIVATED → Bradykinesia / Rigidity / Tremor

Sources: Costanzo Physiology 7th Edition; Neuroanatomy through Clinical Cases 3rd Edition; Harrison's Principles of Internal Medicine 22nd Edition; Stahl's Essential Psychopharmacology; Adams and Victor's Principles of Neurology 12th Edition; Bradley and Daroff's Neurology in Clinical Practice

This is a shared conversation. Sign in to Orris to start your own chat.