from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.lib import colors
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, HRFlowable, ListFlowable, ListItem
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY

OUTPUT_PATH = "/tmp/workspace/cardiac-answers/Cardiac_Cycle_and_Cardiac_Output.pdf"

doc = SimpleDocTemplate(
    OUTPUT_PATH,
    pagesize=A4,
    rightMargin=2*cm,
    leftMargin=2*cm,
    topMargin=2*cm,
    bottomMargin=2*cm,
)

styles = getSampleStyleSheet()

# --- Custom Styles ---
title_style = ParagraphStyle(
    "MainTitle",
    parent=styles["Heading1"],
    fontSize=17,
    textColor=colors.HexColor("#1a237e"),
    spaceAfter=4,
    spaceBefore=0,
    alignment=TA_CENTER,
    fontName="Helvetica-Bold",
)

subtitle_style = ParagraphStyle(
    "SubTitle",
    parent=styles["Normal"],
    fontSize=10,
    textColor=colors.HexColor("#555555"),
    spaceAfter=10,
    alignment=TA_CENTER,
    fontName="Helvetica",
)

q_title_style = ParagraphStyle(
    "QuestionTitle",
    parent=styles["Heading1"],
    fontSize=13,
    textColor=colors.white,
    spaceAfter=0,
    spaceBefore=0,
    leftIndent=8,
    fontName="Helvetica-Bold",
    backColor=colors.HexColor("#1a237e"),
    borderPad=6,
)

section_style = ParagraphStyle(
    "SectionHead",
    parent=styles["Heading2"],
    fontSize=11,
    textColor=colors.HexColor("#0d47a1"),
    spaceBefore=10,
    spaceAfter=2,
    fontName="Helvetica-Bold",
    borderPad=0,
)

subsection_style = ParagraphStyle(
    "SubSection",
    parent=styles["Heading3"],
    fontSize=10.5,
    textColor=colors.HexColor("#1565c0"),
    spaceBefore=7,
    spaceAfter=1,
    fontName="Helvetica-Bold",
)

body_style = ParagraphStyle(
    "Body",
    parent=styles["Normal"],
    fontSize=10,
    textColor=colors.HexColor("#212121"),
    spaceAfter=2,
    spaceBefore=0,
    leading=15,
    fontName="Helvetica",
)

bullet_style = ParagraphStyle(
    "Bullet",
    parent=styles["Normal"],
    fontSize=10,
    textColor=colors.HexColor("#212121"),
    spaceAfter=2,
    spaceBefore=0,
    leading=15,
    leftIndent=14,
    bulletIndent=4,
    fontName="Helvetica",
)

def_style = ParagraphStyle(
    "Definition",
    parent=styles["Normal"],
    fontSize=10,
    textColor=colors.HexColor("#212121"),
    spaceAfter=3,
    spaceBefore=2,
    leading=15,
    leftIndent=10,
    fontName="Helvetica-Oblique",
    backColor=colors.HexColor("#e3f2fd"),
    borderPad=5,
)

mnemonic_style = ParagraphStyle(
    "Mnemonic",
    parent=styles["Normal"],
    fontSize=10.5,
    textColor=colors.HexColor("#4a148c"),
    spaceAfter=3,
    spaceBefore=3,
    leading=16,
    leftIndent=10,
    fontName="Helvetica-Bold",
    backColor=colors.HexColor("#f3e5f5"),
    borderPad=5,
)

flowchart_style = ParagraphStyle(
    "Flowchart",
    parent=styles["Normal"],
    fontSize=10,
    textColor=colors.HexColor("#1b5e20"),
    spaceAfter=2,
    spaceBefore=2,
    leading=16,
    leftIndent=10,
    fontName="Helvetica",
    backColor=colors.HexColor("#e8f5e9"),
    borderPad=5,
)

note_style = ParagraphStyle(
    "Note",
    parent=styles["Normal"],
    fontSize=9.5,
    textColor=colors.HexColor("#b71c1c"),
    spaceAfter=2,
    spaceBefore=2,
    leading=14,
    leftIndent=10,
    fontName="Helvetica-Oblique",
)

def H1(text):
    return Paragraph(f"<b>{text}</b>", q_title_style)

def H2(text):
    return Paragraph(text, section_style)

def H3(text):
    return Paragraph(text, subsection_style)

def B(text):
    return Paragraph(f"&#8226; {text}", bullet_style)

def Def(label, text):
    return Paragraph(f"<b>{label}:</b> {text}", def_style)

def Body(text):
    return Paragraph(text, body_style)

def Mnemonic(text):
    return Paragraph(text, mnemonic_style)

def Flowchart(text):
    return Paragraph(text, flowchart_style)

def Note(text):
    return Paragraph(f"<i>Note: {text}</i>", note_style)

def HR():
    return HRFlowable(width="100%", thickness=0.5, color=colors.HexColor("#bbbbbb"), spaceAfter=6, spaceBefore=6)

def Space(h=6):
    return Spacer(1, h)

story = []

# =========================================================
#  COVER / HEADER
# =========================================================
story.append(Space(10))
story.append(Paragraph("Physiology — University Exam Answers", title_style))
story.append(Paragraph("10 Marks Each  |  Cardiac Cycle  &amp;  Cardiac Output", subtitle_style))
story.append(HR())
story.append(Space(6))

# =========================================================
#  QUESTION 1: CARDIAC CYCLE
# =========================================================
story.append(H1("  Q1.  Write a detailed note on the Cardiac Cycle.  [10 Marks]"))
story.append(Space(8))

# 1. Definition
story.append(H2("1.  Definition"))
story.append(Def("Cardiac Cycle",
    "The sequence of mechanical and electrical events that repeats with every heartbeat, "
    "from the beginning of one heartbeat to the beginning of the next."))
story.append(B("Duration = 60 / Heart Rate.  At 75 beats/min → 0.8 s (800 ms)."))
story.append(B("Initiated by spontaneous action potential in the sinoatrial (SA) node."))
story.append(Space(4))

# 2. Overview of Systole & Diastole
story.append(H2("2.  Systole vs Diastole"))
story.append(B("<b>Systole</b> — Phase of ventricular contraction and ejection."))
story.append(B("<b>Diastole</b> — Phase of ventricular relaxation and filling."))
story.append(B("At a normal rate of 72 beats/min: systole ≈ 0.4 of the cycle; diastole ≈ 0.6."))
story.append(B("As heart rate increases, diastole shortens more than systole → risk of incomplete filling."))
story.append(Space(4))

# 3. Cardiac Valves
story.append(H2("3.  Cardiac Valves — Basics"))
story.append(B("<b>AV (inlet) valves</b> — allow blood from atria → ventricles only."))
story.append(B("Right side: Tricuspid valve (3 cusps).  Left side: Mitral valve (2 cusps / bicuspid)."))
story.append(B("<b>Semilunar (outlet) valves</b> — allow blood from ventricles → great arteries only."))
story.append(B("Pulmonary valve (RV → pulmonary artery); Aortic valve (LV → aorta)."))
story.append(B("All valves open when upstream pressure > downstream pressure (passive opening)."))
story.append(Space(4))

# 4. Seven Phases
story.append(H2("4.  Seven Phases of the Cardiac Cycle (Costanzo Classification)"))
story.append(Mnemonic("Mnemonic — \"A Big, Rapid Ejection, Reduced, Slow, Fills\" → Atrial systole | "
    "Isovolumetric Contraction | Rapid Ejection | Reduced Ejection | "
    "Isovolumetric Relaxation | Rapid Filling | Slow Filling"))
story.append(Space(4))

story.append(H3("Phase A — Atrial Systole"))
story.append(B("Trigger: P wave on ECG (atrial depolarisation)."))
story.append(B("Left atrial pressure rises → 'a' wave on venous pulse."))
story.append(B("Mitral valve is open; atrial contraction pushes final ~20% of blood into ventricle."))
story.append(B("Ventricular volume rises to End-Diastolic Volume (EDV) ≈ 140 mL."))
story.append(B("Heart sound: S4 (not heard in normal adults; audible in ventricular hypertrophy)."))
story.append(Space(3))

story.append(H3("Phase B — Isovolumetric Ventricular Contraction (IVC)"))
story.append(B("Trigger: QRS complex on ECG (ventricular depolarisation)."))
story.append(B("Ventricular pressure rises rapidly; all valves are closed."))
story.append(B("Volume remains constant (isovolumetric) — no ejection yet."))
story.append(B("Mitral valve closes (upstream LV pressure > LA pressure) → <b>S1 heart sound</b>."))
story.append(B("'c' wave on venous pulse (tricuspid valve bulges back)."))
story.append(Space(3))

story.append(H3("Phase C — Rapid Ventricular Ejection"))
story.append(B("LV pressure exceeds aortic pressure → Aortic valve opens."))
story.append(B("Blood ejected rapidly; aortic pressure rises to systolic peak (~120 mmHg)."))
story.append(B("LV volume decreases sharply; LV pressure reaches maximum."))
story.append(B("ECG: peak of T wave at end of this phase."))
story.append(Space(3))

story.append(H3("Phase D — Reduced Ventricular Ejection"))
story.append(B("Ejection continues but at a slower rate."))
story.append(B("LV pressure begins to fall below aortic pressure, but aortic valve stays open momentarily."))
story.append(B("'x' descent seen on venous pulse."))
story.append(Space(3))

story.append(H3("Phase E — Isovolumetric Ventricular Relaxation (IVR)"))
story.append(B("Systole ends; ventricle relaxes → LV pressure falls below aortic pressure."))
story.append(B("Aortic valve closes → <b>S2 heart sound</b> (A2 component).  Dicrotic notch on aortic pressure curve."))
story.append(B("All valves closed; volume remains constant at End-Systolic Volume (ESV) ≈ 70 mL."))
story.append(B("'v' wave builds on venous pulse (veins filling with closed tricuspid valve)."))
story.append(Space(3))

story.append(H3("Phase F — Rapid Ventricular Filling"))
story.append(B("LV pressure < LA pressure → Mitral valve opens."))
story.append(B("Blood rushes in rapidly from atrium.  LV volume rises quickly."))
story.append(B("Heart sound: S3 (pathological in adults > 40 yrs — e.g., heart failure)."))
story.append(B("'y' descent on venous pulse."))
story.append(Space(3))

story.append(H3("Phase G — Slow Ventricular Filling (Diastasis)"))
story.append(B("Passive slow filling as venous return continues."))
story.append(B("Atrial and ventricular pressures nearly equalize."))
story.append(B("Ends when next atrial systole (Phase A) begins."))
story.append(Space(6))

# 5. Pressure events summary
story.append(H2("5.  Key Pressure Values (Left Heart)"))
story.append(B("End-Diastolic Volume (EDV) = 140 mL (normal)."))
story.append(B("End-Systolic Volume (ESV) = 70 mL (normal)."))
story.append(B("Stroke Volume (SV) = EDV − ESV = 70 mL."))
story.append(B("Aortic systolic pressure ≈ 120 mmHg; diastolic pressure ≈ 80 mmHg."))
story.append(B("LV pressure during IVC rises from ~0 to ~80 mmHg; peaks ~120 mmHg during ejection."))
story.append(Space(4))

# 6. Heart sounds summary
story.append(H2("6.  Heart Sounds — Summary"))
story.append(B("<b>S1</b> ('lub') — Closure of Mitral + Tricuspid (AV) valves; marks onset of ventricular systole."))
story.append(B("<b>S2</b> ('dub') — Closure of Aortic + Pulmonary (semilunar) valves; marks end of systole."))
story.append(B("<b>S3</b> — Rapid ventricular filling; pathological in adults (heart failure, dilated cardiomyopathy)."))
story.append(B("<b>S4</b> — Atrial contraction against a stiff/hypertrophied ventricle; always pathological."))
story.append(Space(4))

# 7. ECG correlation
story.append(H2("7.  ECG Correlation"))
story.append(B("<b>P wave</b> → Atrial depolarisation → Atrial systole begins."))
story.append(B("<b>PR interval</b> → AV nodal delay (>0.1 s) — allows atrial emptying before ventricular contraction."))
story.append(B("<b>QRS complex</b> → Ventricular depolarisation → Isovolumetric contraction begins."))
story.append(B("<b>T wave</b> → Ventricular repolarisation → Relaxation phase."))
story.append(Space(4))

# 8. Flowchart
story.append(H2("8.  Flowchart of the Cardiac Cycle"))
story.append(Flowchart(
    "SA Node fires  →  P wave (ECG)  →  Atrial Systole (AV valves open)<br/>"
    "↓<br/>"
    "QRS complex  →  Ventricular depolarisation  →  IVC (all valves closed, volume constant)<br/>"
    "↓<br/>"
    "LV pressure > Aortic pressure  →  Aortic valve opens  →  Rapid Ejection (Phase C)<br/>"
    "↓<br/>"
    "Reduced Ejection (Phase D)  →  T wave (repolarisation)<br/>"
    "↓<br/>"
    "LV pressure < Aortic pressure  →  Aortic valve closes  →  S2 sound  →  IVR (all valves closed)<br/>"
    "↓<br/>"
    "LV pressure < LA pressure  →  Mitral valve opens  →  Rapid Filling (S3) → Slow Filling<br/>"
    "↓<br/>"
    "Next P wave  →  Cycle repeats"
))
story.append(Space(6))

story.append(Note("At higher heart rates, diastole shortens disproportionately, limiting ventricular filling "
    "and potentially reducing stroke volume."))

story.append(HR())
story.append(Space(12))

# =========================================================
#  QUESTION 2: CARDIAC OUTPUT
# =========================================================
story.append(H1("  Q2.  Write a detailed note on Cardiac Output.  [10 Marks]"))
story.append(Space(8))

# 1. Definition
story.append(H2("1.  Definition"))
story.append(Def("Cardiac Output (CO)",
    "The total volume of blood ejected by the heart per minute. "
    "It equals Stroke Volume × Heart Rate."))
story.append(B("Normal CO ≈ 5,000 mL/min (5 L/min) in a 70 kg adult at rest."))
story.append(B("Based on: SV = 70 mL × HR = 72 beats/min ≈ 5040 mL/min."))
story.append(Space(3))
story.append(Def("Cardiac Index (CI)",
    "Cardiac output corrected for body surface area (BSA). CI = CO / BSA. Normal = 2.5–4.0 L/min/m²."))
story.append(Space(4))

# 2. Formula
story.append(H2("2.  Formula"))
story.append(Body("<b>CO = Stroke Volume (SV)  ×  Heart Rate (HR)</b>"))
story.append(Body("<b>SV = End-Diastolic Volume (EDV) − End-Systolic Volume (ESV)</b>"))
story.append(Body("<b>Ejection Fraction (EF) = SV / EDV  ×  100%</b>  (Normal: 55–70%)"))
story.append(Space(2))
story.append(B("Example: EDV = 140 mL, ESV = 70 mL → SV = 70 mL; HR = 75 → CO = 5250 mL/min; EF = 50%."))
story.append(Space(4))

# 3. Determinants
story.append(H2("3.  Determinants of Cardiac Output"))
story.append(Body("CO is regulated by four major factors:"))
story.append(Mnemonic("Mnemonic:  <b>PACH</b>  →  Preload | Afterload | Contractility | Heart Rate"))
story.append(Space(4))

story.append(H3("A.  Preload"))
story.append(Def("Preload",
    "The degree to which sarcomeres are stretched just before systole; "
    "clinically measured as End-Diastolic Volume (EDV) or End-Diastolic Pressure (EDP)."))
story.append(B("Determined by: venous return, blood volume, atrial contraction."))
story.append(B("↑ Preload → ↑ EDV → ↑ SV (Frank-Starling Law)."))
story.append(B("↓ Preload (haemorrhage, dehydration) → ↓ EDV → ↓ CO."))
story.append(B("LVEDP > 20–25 mmHg → pulmonary oedema."))
story.append(Space(3))

story.append(H3("B.  Afterload"))
story.append(Def("Afterload",
    "The tension/resistance the ventricle must overcome to eject blood; "
    "determined by aortic pressure and total peripheral resistance (TPR)."))
story.append(B("Laplace's Law: Wall tension = (Pressure × Radius) / (2 × Wall thickness)."))
story.append(B("↑ Afterload (hypertension, aortic stenosis) → ↓ SV → ↓ CO."))
story.append(B("↓ Afterload (vasodilators) → ↑ SV → ↑ CO."))
story.append(B("TPR = (MAP − CVP) / CO."))
story.append(Space(3))

story.append(H3("C.  Contractility (Inotropy)"))
story.append(Def("Contractility",
    "The intrinsic ability of the myocardium to generate force, "
    "independent of preload and afterload. Also called inotropy."))
story.append(B("↑ Contractility (positive inotropes: adrenaline, digoxin, dopamine) → ↑ SV → ↑ CO."))
story.append(B("↓ Contractility (negative inotropes: beta-blockers, heart failure) → ↓ SV → ↓ CO."))
story.append(B("Increased contractility → ↑ Ejection Fraction at the same preload."))
story.append(Space(3))

story.append(H3("D.  Heart Rate"))
story.append(B("↑ Heart rate → ↑ CO (up to a limit)."))
story.append(B("Very high HR (tachycardia) → diastole shortens → ↓ filling → ↓ SV → overall CO may fall."))
story.append(B("Controlled by: autonomic nervous system (sympathetic ↑ HR; parasympathetic ↓ HR)."))
story.append(Space(4))

# 4. Frank-Starling Law
story.append(H2("4.  Frank-Starling Law of the Heart"))
story.append(Def("Frank-Starling Law",
    "The stroke volume (and cardiac output) ejected by the ventricle is directly proportional "
    "to the end-diastolic volume. In other words, the more the heart fills during diastole, "
    "the more forcefully it contracts and the more blood it ejects in systole."))
story.append(B("Cellular basis: Increased fibre length → optimal actin-myosin overlap → stronger contraction."))
story.append(B("Ensures: CO = venous return in the steady state (input = output balance)."))
story.append(B("Positive inotropes shift the Frank-Starling curve upward (more SV for same EDV)."))
story.append(B("Negative inotropes shift the curve downward."))
story.append(Space(4))

# 5. Measurement
story.append(H2("5.  Measurement of Cardiac Output"))
story.append(Space(2))

story.append(H3("A.  Fick Principle (Gold Standard)"))
story.append(Def("Fick Principle",
    "Cardiac output can be calculated by dividing the total oxygen consumption of the body "
    "by the arterio-venous oxygen difference across the lungs."))
story.append(Body("<b>CO = O₂ Consumption / ([O₂] Pulmonary Vein − [O₂] Pulmonary Artery)</b>"))
story.append(B("Normal O₂ consumption ≈ 250 mL O₂/min."))
story.append(B("O₂ content of pulmonary venous blood ≈ 0.20 mL O₂/mL blood."))
story.append(B("O₂ content of pulmonary arterial (mixed venous) blood ≈ 0.15 mL O₂/mL blood."))
story.append(B("CO = 250 / (0.20 − 0.15) = 250 / 0.05 = <b>5000 mL/min</b>."))
story.append(B("Pulmonary arterial O₂ is sampled via a pulmonary artery catheter (right heart catheterisation)."))
story.append(Space(3))

story.append(H3("B.  Thermodilution Method (Clinically Used)"))
story.append(B("Cold saline injected into right atrium; temperature change measured in pulmonary artery."))
story.append(B("CO inversely proportional to the area under the temperature-time curve."))
story.append(B("Performed via Swan-Ganz (pulmonary artery) catheter."))
story.append(Space(3))

story.append(H3("C.  Echocardiography (Non-Invasive)"))
story.append(B("CO = SV × HR, where SV is measured by Doppler flow across aortic valve."))
story.append(B("Most widely used non-invasive method in clinical practice."))
story.append(Space(4))

# 6. Regulation
story.append(H2("6.  Regulation of Cardiac Output"))
story.append(Space(2))
story.append(H3("A.  Autonomic Nervous System"))
story.append(B("Sympathetic stimulation → ↑ HR (chronotropy) + ↑ contractility (inotropy) → ↑ CO."))
story.append(B("Parasympathetic (vagal) stimulation → ↓ HR (negative chronotropy) → ↓ CO."))
story.append(Space(2))

story.append(H3("B.  Hormonal Regulation"))
story.append(B("Adrenaline (epinephrine) → ↑ HR + ↑ contractility → ↑ CO (fight-or-flight)."))
story.append(B("Thyroid hormones → ↑ CO (↑ metabolic demand, ↑ HR)."))
story.append(B("Renin-Angiotensin-Aldosterone System (RAAS) → ↑ blood volume → ↑ preload → ↑ CO."))
story.append(Space(2))

story.append(H3("C.  Venous Return"))
story.append(B("In steady state, CO = Venous Return (governed by Frank-Starling Law)."))
story.append(B("Factors increasing venous return: muscle pump, respiratory pump, venoconstriction, ↑ blood volume."))
story.append(Space(4))

# 7. Exercise Response
story.append(H2("7.  Cardiac Output in Exercise"))
story.append(B("CO can rise up to 6-fold during strenuous exercise (≈ 25–30 L/min in trained athletes)."))
story.append(B("Achieved by: ↑ HR (up to 170–200 bpm) + ↑ contractility via sympathetic activation."))
story.append(B("Arterial vasodilation reduces afterload, aiding ejection."))
story.append(B("Venous return increases (muscle pump) → ↑ preload → ↑ SV (Frank-Starling)."))
story.append(B("O₂ demand met partly by increased CO, partly by ↑ O₂ extraction in muscles."))
story.append(Space(4))

# 8. Flowchart
story.append(H2("8.  Summary Flowchart — Factors Affecting Cardiac Output"))
story.append(Flowchart(
    "↑ Venous Return  →  ↑ EDV  →  ↑ Preload  →  ↑ SV (Frank-Starling)  →  ↑ CO<br/>"
    "↑ Contractility (sympathetic / inotropes)  →  ↑ SV  →  ↑ CO<br/>"
    "↓ Afterload (vasodilators)  →  ↑ SV  →  ↑ CO<br/>"
    "↑ Heart Rate (sympathetic)  →  ↑ CO  [but very high HR → ↓ filling → ↓ SV → no net gain]<br/>"
    "CO = SV × HR  →  Normal ≈ 5 L/min"
))
story.append(Space(6))

story.append(Note("Ejection fraction (EF) is a key clinical measure of ventricular contractility. "
    "EF < 40% defines heart failure with reduced ejection fraction (HFrEF)."))

story.append(HR())
story.append(Space(6))
story.append(Paragraph(
    "Sources: Costanzo Physiology 7e | Guyton &amp; Hall Medical Physiology | "
    "Harrison's Principles of Internal Medicine 22e | Goldman-Cecil Medicine",
    ParagraphStyle("source", parent=styles["Normal"], fontSize=8,
                   textColor=colors.grey, alignment=TA_CENTER)
))

doc.build(story)
print(f"PDF saved to: {OUTPUT_PATH}")