from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm, mm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    KeepTogether, Image as RLImage, HRFlowable
)
from reportlab.platypus.flowables import Flowable
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont
from reportlab.graphics.shapes import Drawing, Rect, String, Line, Arrow
from reportlab.graphics import renderPDF
import os

# ── page setup ──────────────────────────────────────────────────────────────
PAGE_W, PAGE_H = A4          # 595.27 x 841.89 pt
LM = RM = 1.4 * cm
TM = BM = 1.5 * cm
CONTENT_W = PAGE_W - LM - RM

# ── colours ─────────────────────────────────────────────────────────────────
C_DARK_BLUE   = colors.HexColor("#0D2B5E")
C_MID_BLUE    = colors.HexColor("#1A4A8A")
C_LIGHT_BLUE  = colors.HexColor("#D6E4F7")
C_ACCENT      = colors.HexColor("#E8501A")
C_HEADER_BG   = colors.HexColor("#1A4A8A")
C_ROW_ALT     = colors.HexColor("#EEF4FB")
C_ROW_HEAD    = colors.HexColor("#C4D9F0")
C_WHITE       = colors.white
C_BLACK       = colors.black
C_GREY        = colors.HexColor("#555555")
C_LIGHT_GREY  = colors.HexColor("#F5F5F5")
C_ARROW       = colors.HexColor("#1A4A8A")
C_BOX_BG      = colors.HexColor("#EEF4FB")

# ── styles ───────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

TITLE = S("TITLE",
    fontSize=15, leading=18, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_CENTER,
    spaceAfter=2)

H1 = S("H1",
    fontSize=12, leading=14, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_LEFT,
    spaceBefore=4, spaceAfter=2)

H2 = S("H2",
    fontSize=10, leading=12.5, textColor=C_MID_BLUE,
    fontName="Helvetica-Bold", alignment=TA_LEFT,
    spaceBefore=5, spaceAfter=1)

H3 = S("H3",
    fontSize=9, leading=11, textColor=C_DARK_BLUE,
    fontName="Helvetica-Bold", alignment=TA_LEFT,
    spaceBefore=3, spaceAfter=1)

BODY = S("BODY",
    fontSize=9, leading=11.5, textColor=C_BLACK,
    fontName="Helvetica", alignment=TA_LEFT,
    spaceAfter=1)

BODY_BOLD = S("BODY_BOLD",
    fontSize=9, leading=11.5, textColor=C_BLACK,
    fontName="Helvetica-Bold", alignment=TA_LEFT,
    spaceAfter=1)

BULLET = S("BULLET",
    fontSize=9, leading=11.5, textColor=C_BLACK,
    fontName="Helvetica", alignment=TA_LEFT,
    leftIndent=10, bulletIndent=2,
    spaceAfter=1)

BULLET2 = S("BULLET2",
    fontSize=9, leading=11.5, textColor=C_BLACK,
    fontName="Helvetica", alignment=TA_LEFT,
    leftIndent=22, bulletIndent=14,
    spaceAfter=1)

CAPTION = S("CAPTION",
    fontSize=8, leading=10, textColor=C_GREY,
    fontName="Helvetica-Oblique", alignment=TA_CENTER,
    spaceAfter=2)

FOOTER_STYLE = S("FOOTER",
    fontSize=7.5, leading=9, textColor=C_GREY,
    fontName="Helvetica", alignment=TA_CENTER)

CELL = S("CELL",
    fontSize=8.5, leading=10.5, textColor=C_BLACK,
    fontName="Helvetica", alignment=TA_LEFT)

CELL_BOLD = S("CELL_BOLD",
    fontSize=8.5, leading=10.5, textColor=C_DARK_BLUE,
    fontName="Helvetica-Bold", alignment=TA_LEFT)

CELL_HEAD = S("CELL_HEAD",
    fontSize=8.5, leading=10.5, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_CENTER)

# ── helpers ──────────────────────────────────────────────────────────────────
def b(text): return f"<b>{text}</b>"
def i(text): return f"<i>{text}</i>"
def bi(text): return f"<b><i>{text}</i></b>"

def section_header(title, emoji=""):
    """Blue bar section header as a Table row."""
    label = f"{emoji}  {title}" if emoji else title
    data = [[Paragraph(label, H1)]]
    t = Table(data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND', (0,0), (-1,-1), C_HEADER_BG),
        ('LEFTPADDING',  (0,0), (-1,-1), 6),
        ('RIGHTPADDING', (0,0), (-1,-1), 6),
        ('TOPPADDING',   (0,0), (-1,-1), 4),
        ('BOTTOMPADDING',(0,0), (-1,-1), 4),
        ('ROUNDEDCORNERS', [4]),
    ]))
    return t

def sub_header(title):
    return Paragraph(title, H2)

def sub3(title):
    return Paragraph(title, H3)

def body(text):
    return Paragraph(text, BODY)

def bullet(text, level=1):
    style = BULLET if level == 1 else BULLET2
    bullet_char = "•" if level == 1 else "–"
    return Paragraph(f"{bullet_char}  {text}", style)

def sp(h=4):
    return Spacer(1, h)

def make_table(headers, rows, col_widths=None, zebra=True):
    """Create a bordered table with header row."""
    if col_widths is None:
        n = len(headers)
        col_widths = [CONTENT_W / n] * n

    data = [[Paragraph(h, CELL_HEAD) for h in headers]]
    for i, row in enumerate(rows):
        data.append([Paragraph(str(c), CELL) for c in row])

    t = Table(data, colWidths=col_widths)
    style = [
        # header
        ('BACKGROUND',    (0,0), (-1,0),  C_HEADER_BG),
        ('TEXTCOLOR',     (0,0), (-1,0),  C_WHITE),
        ('FONTNAME',      (0,0), (-1,0),  'Helvetica-Bold'),
        ('FONTSIZE',      (0,0), (-1,0),  8.5),
        ('ALIGN',         (0,0), (-1,0),  'CENTER'),
        # body
        ('FONTNAME',      (0,1), (-1,-1), 'Helvetica'),
        ('FONTSIZE',      (0,1), (-1,-1), 8.5),
        ('ALIGN',         (0,1), (-1,-1), 'LEFT'),
        # grid
        ('GRID',          (0,0), (-1,-1), 0.5, colors.HexColor("#B0C8E8")),
        ('BOX',           (0,0), (-1,-1), 1,   C_MID_BLUE),
        # padding
        ('LEFTPADDING',   (0,0), (-1,-1), 5),
        ('RIGHTPADDING',  (0,0), (-1,-1), 5),
        ('TOPPADDING',    (0,0), (-1,-1), 3),
        ('BOTTOMPADDING', (0,0), (-1,-1), 3),
        ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
    ]
    if zebra:
        for r in range(1, len(data)):
            if r % 2 == 0:
                style.append(('BACKGROUND', (0,r), (-1,r), C_ROW_ALT))
    t.setStyle(TableStyle(style))
    return t

def flow_chart(steps, arrow="→"):
    """Render a horizontal flowchart as a table of steps connected by arrows."""
    # Build single row: [step, arrow, step, arrow, ...]
    items = []
    for idx, step in enumerate(steps):
        items.append(step)
        if idx < len(steps) - 1:
            items.append(arrow)

    # Decide col widths
    n_steps  = len(steps)
    n_arrows = n_steps - 1
    step_w   = (CONTENT_W - n_arrows * 1.0*cm) / n_steps

    col_widths = []
    for idx in range(len(items)):
        col_widths.append(step_w if idx % 2 == 0 else 1.0*cm)

    data_row = []
    for idx, item in enumerate(items):
        if idx % 2 == 0:
            data_row.append(Paragraph(item, S(f"FC{idx}", fontSize=8.5,
                leading=10.5, fontName="Helvetica", alignment=TA_CENTER,
                textColor=C_DARK_BLUE)))
        else:
            data_row.append(Paragraph(item, S(f"AR{idx}", fontSize=11,
                leading=12, fontName="Helvetica-Bold",
                alignment=TA_CENTER, textColor=C_ACCENT)))

    t = Table([data_row], colWidths=col_widths)
    style_cmds = [
        ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
        ('ALIGN',         (0,0), (-1,-1), 'CENTER'),
        ('LEFTPADDING',   (0,0), (-1,-1), 4),
        ('RIGHTPADDING',  (0,0), (-1,-1), 4),
        ('TOPPADDING',    (0,0), (-1,-1), 5),
        ('BOTTOMPADDING', (0,0), (-1,-1), 5),
    ]
    for idx in range(0, len(items), 2):
        col = idx
        style_cmds.append(('BACKGROUND',  (col,0), (col,0), C_BOX_BG))
        style_cmds.append(('BOX',         (col,0), (col,0), 0.6, C_MID_BLUE))
        style_cmds.append(('ROUNDEDCORNERS', [3]))
    t.setStyle(TableStyle(style_cmds))
    return t

def note_box(text):
    """Highlighted note box."""
    data = [[Paragraph(f"📌 {text}", S("NB",
        fontSize=8.5, leading=10.5,
        fontName="Helvetica-Bold",
        textColor=C_DARK_BLUE))]]
    t = Table(data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',    (0,0), (-1,-1), colors.HexColor("#FFF3CD")),
        ('BOX',           (0,0), (-1,-1), 0.8, colors.HexColor("#E8A000")),
        ('LEFTPADDING',   (0,0), (-1,-1), 6),
        ('RIGHTPADDING',  (0,0), (-1,-1), 6),
        ('TOPPADDING',    (0,0), (-1,-1), 4),
        ('BOTTOMPADDING', (0,0), (-1,-1), 4),
    ]))
    return t

def fit_image(path, max_w, max_h):
    """Return a ReportLab Image scaled to fit within max_w x max_h."""
    from PIL import Image as PILImage
    pil = PILImage.open(path)
    w, h = pil.size
    ratio = min(max_w / w, max_h / h)
    return RLImage(path, width=w*ratio, height=h*ratio)

# ── footer ────────────────────────────────────────────────────────────────────
def footer_canvas(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 7.5)
    canvas.setFillColor(C_GREY)
    footer_text = "Made By Sohaib Khan  |  SMC 5"
    canvas.drawCentredString(PAGE_W / 2, BM * 0.55, footer_text)
    # thin line above footer
    canvas.setStrokeColor(colors.HexColor("#CCCCCC"))
    canvas.setLineWidth(0.5)
    canvas.line(LM, BM * 0.8, PAGE_W - RM, BM * 0.8)
    # page number right
    canvas.drawRightString(PAGE_W - RM, BM * 0.55, f"Page {doc.page}")
    canvas.restoreState()

# ── document build ─────────────────────────────────────────────────────────
IMG_DIR = "/tmp/workspace/achondroplasia"
OUT_PATH = "/tmp/workspace/achondroplasia/Achondroplasia_Notes.pdf"

doc = SimpleDocTemplate(
    OUT_PATH,
    pagesize=A4,
    leftMargin=LM, rightMargin=RM,
    topMargin=TM, bottomMargin=BM + 0.8*cm,
    title="Achondroplasia – Structured Study Notes",
    author="Sohaib Khan SMC 5",
)

story = []

# ══════════════════════════════════════════════════════════════════════════════
# TITLE BLOCK
# ══════════════════════════════════════════════════════════════════════════════
title_data = [[Paragraph("🦴  ACHONDROPLASIA", TITLE)],
              [Paragraph("Structured Study Notes  |  Skeletal Dysplasia", S("SUB",
                  fontSize=9, leading=11, textColor=colors.HexColor("#A8C8F0"),
                  fontName="Helvetica-Oblique", alignment=TA_CENTER))]]
title_table = Table(title_data, colWidths=[CONTENT_W])
title_table.setStyle(TableStyle([
    ('BACKGROUND',    (0,0), (-1,-1), C_DARK_BLUE),
    ('LEFTPADDING',   (0,0), (-1,-1), 8),
    ('RIGHTPADDING',  (0,0), (-1,-1), 8),
    ('TOPPADDING',    (0,0), (-1,-1), 8),
    ('BOTTOMPADDING', (0,0), (-1,-1), 8),
]))
story.append(title_table)
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 1  INTRODUCTION & DEFINITION
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("1. INTRODUCTION & DEFINITION", "📖"))
story.append(sp(3))

# lecture image alongside intro text
img1 = fit_image(os.path.join(IMG_DIR, "img1_lecture.jpg"), max_w=7.5*cm, max_h=5*cm)

intro_text = [
    [Paragraph(
        "<b>Definition:</b>  Achondroplasia is the <b><i>most common form of disproportionate dwarfism</i></b>, "
        "particularly prevalent in India.", BODY),
     sp(2),
     Paragraph("<b>Type:</b>  Skeletal dysplasia (failure of endochondral ossification).", BODY),
     sp(2),
     Paragraph(
         "<b>Clinical Importance:</b>  Frequently featured in <b>NEET PG examinations</b> – at least "
         "one question every alternate year.", BODY),
    ]
]

# side-by-side: text left, image right
col_text = CONTENT_W - 8*cm
row_data = [[
    [
        Paragraph("<b>Definition:</b>  Achondroplasia is the "
                  "<b><i>most common form of disproportionate dwarfism</i></b>, "
                  "particularly prevalent in India.", BODY),
        sp(3),
        Paragraph("<b>Type:</b>  Skeletal dysplasia.", BODY),
        sp(3),
        Paragraph("<b>Clinical Importance:</b>  Frequently featured in <b>NEET PG examinations</b> – "
                  "at least one question every alternate year.", BODY),
        sp(3),
        Paragraph(
            "<b>Cause:</b>  Defect in <b><i>endochondral ossification</i></b> – the process responsible "
            "for lengthening bones, primarily affecting <b>long bones</b>.", BODY),
        sp(3),
        Paragraph(
            "<b>Intramembranous ossification</b> (clavicle, skull, trunk) remains <b>normal</b>.", BODY),
    ],
    img1,
]]
layout = Table(row_data, colWidths=[col_text, 7.8*cm])
layout.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'TOP'),
    ('LEFTPADDING',   (0,0), (-1,-1), 0),
    ('RIGHTPADDING',  (0,0), (-1,-1), 0),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
story.append(layout)
story.append(Paragraph("<i>Fig 1: Achondroplasia – Skeletal Dysplasia lecture overview</i>", CAPTION))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 2  GENETIC BASIS & INHERITANCE
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("2. GENETIC BASIS & INHERITANCE", "🧬"))
story.append(sp(4))

story.append(sub_header("2a. Inheritance Pattern"))
story.append(bullet(b("Autosomal Dominant") + " inheritance."))
story.append(bullet(bi(">80% of cases") + " result from " + b("new mutations") + " (sporadic) – not inherited."))
story.append(sp(3))

story.append(sub_header("2b. Gene Involved"))
story.append(bullet("Mutation in the " + bi("FGFR3 gene") + " (Fibroblast Growth Factor Receptor 3)."))
story.append(bullet(b("Important differential:") + "  " + b("FGFR2") + " gene mutation causes " + bi("Apert syndrome") + ", NOT achondroplasia."))
story.append(sp(4))

story.append(sub_header("2c. Gene–Condition Comparison Table"))
story.append(sp(2))

gene_headers = ["Gene", "Condition Associated", "Notes"]
gene_rows = [
    [b("FGFR3"),       bi("Achondroplasia"),        "Most common cause"],
    ["FGFR2",          "Apert syndrome",             "Different skeletal disorder"],
    ["Fibrillin-1",    "Marfan syndrome",            "Not related to achondroplasia"],
    ["COL5A1 (Type 1 Collagen)", "Osteogenesis Imperfecta", "Not related"],
    ["NOTCH1",         "Some leukemias",             "No orthopedic connection"],
]
story.append(make_table(gene_headers, gene_rows,
    col_widths=[5.5*cm, 6.5*cm, CONTENT_W - 12*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 3  RISK FACTORS
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("3. RISK FACTORS", "⚠️"))
story.append(sp(4))

rf_headers = ["Risk Factor", "Association", "Note"]
rf_rows = [
    [bi("Paternal Age > 36 years"), b("Achondroplasia") + "  (risk increases)", "New FGFR3 mutations more common with older fathers"],
    ["High Maternal Age", "Down syndrome", b("NOT") + " associated with achondroplasia"],
]
story.append(make_table(rf_headers, rf_rows,
    col_widths=[5.5*cm, 5.5*cm, CONTENT_W - 11*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 4  PATHOPHYSIOLOGY & BONE OSSIFICATION
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("4. PATHOPHYSIOLOGY & BONE OSSIFICATION", "🔬"))
story.append(sp(4))

story.append(sub_header("4a. Ossification Types"))

oss_headers = ["Ossification Type", "Status in Achondroplasia", "Structures Affected"]
oss_rows = [
    [bi("Endochondral Ossification"), b("DEFECTIVE"), "Long bones – arms, legs (lengthening affected)"],
    [bi("Intramembranous Ossification"), b("NORMAL"), "Skull, clavicle, trunk (appear normal/relatively larger)"],
]
story.append(make_table(oss_headers, oss_rows,
    col_widths=[5.5*cm, 4.5*cm, CONTENT_W - 10*cm]))
story.append(sp(4))

story.append(sub_header("4b. Pathophysiology Flowchart"))
story.append(sp(3))
story.append(flow_chart([
    "FGFR3 Mutation",
    "Defective\nEndochondral\nOssification",
    "Impaired\nLong Bone\nLengthening",
    "Proximal\nLimb\nShortening",
    "Rhizomelic\nDwarfism",
]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 5  CLINICAL FEATURES & MORPHOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("5. CLINICAL FEATURES & MORPHOLOGY", "🩺"))
story.append(sp(4))

story.append(sub_header("5a. Body Proportions & Growth Patterns"))
story.append(bullet(b("Dwarfism Type:") + "  " + bi("Rhizomelic dwarfism") + " – shortening predominantly of the " + b("proximal limbs") + " (upper arms and thighs)."))
story.append(bullet(b("Limb Proportions:")))
story.append(bullet("Shortened " + b("upper limbs") + " more than forearms.", level=2))
story.append(bullet(b("Normal trunk length") + " due to normal intramembranous ossification.", level=2))
story.append(bullet(b("Arm span is decreased."), level=2))
story.append(bullet(b("Head and Face:")))
story.append(bullet(bi("Macrocephaly") + " (large head size).", level=2))
story.append(bullet(bi("Frontal bossing:") + " prominent forehead.", level=2))
story.append(bullet("Peculiar nose shape due to normal nasal bone.", level=2))
story.append(bullet(b("No mental retardation") + " – cognitive function is normal."))
story.append(sp(4))

story.append(sub_header("5b. Skeletal Characteristics – Summary Table"))
story.append(sp(2))

skel_headers = ["Structure / Feature", "Description"]
skel_rows = [
    [b("Skull"),       "Large (" + bi("macrocephaly") + "), frontal bossing; " + bi("Foramen magnum is narrow")] ,
    [b("Limbs"),       "Short, stocky tubular bones"],
    [b("Trunk"),       "Normal size, maintains normal length"],
    [b("Hands"),       bi("Trident hand") + " – middle & ring finger divergence; " + bi("starfish appearance") + " due to uniform finger length"],
    [b("Pelvis"),      bi("Champagne glass appearance") + ": pelvis wider than long; complicates vaginal delivery"],
    [b("Vertebrae"),   bi("Bullet-shaped (beaked) vertebrae") + "; scalloping of vertebrae"],
    [b("Spine"),       "Foramen magnum is narrow; scalloping of vertebrae"],
]
story.append(make_table(skel_headers, skel_rows,
    col_widths=[4.5*cm, CONTENT_W - 4.5*cm]))
story.append(sp(4))

# ── 5c Trident / Starfish Hand ───────────────────────────────────────────────
story.append(sub_header("5c. Hand Appearance – Trident / Starfish Sign 🤚"))
story.append(sp(3))

img2 = fit_image(os.path.join(IMG_DIR, "img2_trident_hand.jpg"), max_w=5*cm, max_h=6*cm)

hand_text = [
    Paragraph(bullet("Middle finger is shortened.", level=1).text if False else
              "•  Middle finger is shortened.", BULLET),
    Paragraph("•  The thumb does not appear much shorter → fingers appear of " + b("similar length") + ".", BULLET),
    Paragraph("•  This mimics the look of a " + bi("trident") + " or " + bi("starfish") + ".", BULLET),
    Paragraph("•  The " + b("ring and middle fingers diverge") + ", creating a trident-like hand.", BULLET),
]

hand_layout = Table(
    [[hand_text, img2]],
    colWidths=[CONTENT_W - 5.5*cm, 5.5*cm]
)
hand_layout.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
    ('LEFTPADDING',   (0,0), (-1,-1), 0),
    ('RIGHTPADDING',  (0,0), (-1,-1), 0),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
story.append(hand_layout)
story.append(Paragraph("<i>Fig 2: Trident / Starfish hand in Achondroplasia</i>", CAPTION))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 6  RADIOLOGICAL FEATURES
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("6. RADIOLOGICAL FEATURES", "🩻"))
story.append(sp(4))

story.append(sub_header("6a. Radiological Features Table"))
story.append(sp(2))
rad_headers = ["Radiological Feature", "Description & Clinical Relevance"]
rad_rows = [
    [bi("Bullet-shaped (beaked) vertebrae"), "Vertebrae appear beaked on lateral X-rays; also described as scalloping"],
    [bi("Trident hand"),                    "Diverged fingers, especially middle & ring fingers"],
    [bi("Short, broad tubular bones"),       "Tibia, femur, humerus appear short and thick"],
    [bi("Champagne glass pelvis"),           "Broad iliac wings, narrow pelvic inlet – impacts vaginal delivery"],
]
story.append(make_table(rad_headers, rad_rows,
    col_widths=[5.5*cm, CONTENT_W - 5.5*cm]))
story.append(sp(5))

story.append(sub_header("6b. Champagne Glass Pelvis"))
story.append(sp(3))
img3 = fit_image(os.path.join(IMG_DIR, "img3_champagne_pelvis.png"), max_w=CONTENT_W, max_h=6.5*cm)
story.append(img3)
story.append(Paragraph("<i>Fig 3: Champagne Glass Pelvis – X-ray showing broad iliac wings with narrow pelvic inlet (arrows), compared to champagne glass shape</i>", CAPTION))
story.append(sp(5))

story.append(sub_header("6c. Bullet-Shaped (Beaked) Vertebrae"))
story.append(sp(3))
img4 = fit_image(os.path.join(IMG_DIR, "img4_bullet_vertebrae.jpg"), max_w=6*cm, max_h=8*cm)
vert_text = [
    Paragraph("•  Vertebrae appear " + bi("beaked / bullet-shaped") + " on lateral X-ray.", BULLET),
    sp(3),
    Paragraph("•  This is a " + b("hallmark radiological sign") + " of achondroplasia.", BULLET),
    sp(3),
    Paragraph("•  Also described as " + bi("scalloping of vertebrae") + ".", BULLET),
    sp(3),
    Paragraph("•  White arrows (solid) point to beaked vertebrae;", BULLET),
    Paragraph("   outlined arrows point to adjacent affected segments.", BULLET2),
]
vert_layout = Table([[vert_text, img4]],
    colWidths=[CONTENT_W - 6.5*cm, 6.5*cm])
vert_layout.setStyle(TableStyle([
    ('VALIGN',        (0,0), (-1,-1), 'MIDDLE'),
    ('LEFTPADDING',   (0,0), (-1,-1), 0),
    ('RIGHTPADDING',  (0,0), (-1,-1), 0),
    ('TOPPADDING',    (0,0), (-1,-1), 0),
    ('BOTTOMPADDING', (0,0), (-1,-1), 0),
]))
story.append(vert_layout)
story.append(Paragraph("<i>Fig 4: Lateral spine X-ray showing bullet/beaked vertebrae in Achondroplasia</i>", CAPTION))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 7  CLINICAL COMPLICATIONS
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("7. CLINICAL COMPLICATIONS", "⚕️"))
story.append(sp(4))

story.append(sub_header("7a. Reproductive Challenges"))
story.append(bullet("Difficulty in " + b("vaginal delivery") + " due to pelvic abnormalities (champagne glass pelvis)."))
story.append(bullet(bi("Cesarean section") + " commonly required for childbirth."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 8  SUMMARY TABLE
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("8. KEY SUMMARY – DISTINGUISHING FEATURES", "📋"))
story.append(sp(4))

sum_headers = ["Aspect", "Achondroplasia"]
sum_rows = [
    [b("Inheritance"),           "Autosomal dominant (majority " + bi("new mutations") + ")"],
    [b("Gene"),                  bi("FGFR3")],
    [b("Ossification Defect"),   bi("Endochondral") + " (affects long bones)"],
    [b("Limb Proportion"),       bi("Rhizomelic shortening") + " (upper limbs more affected)"],
    [b("Skull / Trunk"),         "Normal size (intramembranous ossification unaffected); " + b("foramen magnum narrow")],
    [b("Radiology"),             "Bullet vertebrae, trident hand, champagne pelvis"],
    [b("Cognitive Impact"),      b("No mental retardation")],
    [b("Delivery"),              b("Cesarean section") + " often required"],
    [b("Paternal Age Risk"),     "Father > " + bi("36 years") + " → increased risk of new FGFR3 mutation"],
]
story.append(make_table(sum_headers, sum_rows,
    col_widths=[5*cm, CONTENT_W - 5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 9  COMMON Q&A  (without exam labels)
# ══════════════════════════════════════════════════════════════════════════════
story.append(section_header("9. COMMON QUESTIONS & ANSWERS", "❓"))
story.append(sp(4))

qa_headers = ["Question", "Correct Answer / Explanation"]
qa_rows = [
    ["Mutation responsible for achondroplasia",    bi("FGFR3 gene")],
    ["Gene causing Marfan syndrome",               bi("Fibrillin-1 gene")],
    ["Mode of inheritance",                        b("Autosomal dominant")],
    ["Presence of mental retardation",             b("Absent") + " in achondroplasia"],
    ["Characteristic hand appearance",             bi("Trident / Starfish hand")],
    ["Pelvic shape",                               bi("Champagne glass pelvis") + " – complicates vaginal delivery"],
]
story.append(make_table(qa_headers, qa_rows,
    col_widths=[8*cm, CONTENT_W - 8*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# NOTE BOX
# ══════════════════════════════════════════════════════════════════════════════
story.append(note_box(
    "Key differentials: FGFR3 → Achondroplasia  |  FGFR2 → Apert Syndrome  |  "
    "Fibrillin-1 → Marfan  |  COL5A1 → Osteogenesis Imperfecta  |  "
    "High MATERNAL age → Down Syndrome (NOT Achondroplasia)"
))

# ── build ─────────────────────────────────────────────────────────────────────
doc.build(story, onFirstPage=footer_canvas, onLaterPages=footer_canvas)
print(f"PDF written: {OUT_PATH}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/achondroplasia/build_pdf.py'

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    KeepTogether, Image as RLImage,
)
import os

PAGE_W, PAGE_H = A4
LM = RM = 1.4 * cm
TM = BM = 1.5 * cm
CONTENT_W = PAGE_W - LM - RM

# ── colours ──────────────────────────────────────────────────────────────────
C_DARK      = colors.HexColor("#1A3A5C")
C_MID       = colors.HexColor("#1F5FA6")
C_LIGHT     = colors.HexColor("#D6E8FA")
C_ACCENT    = colors.HexColor("#C0392B")
C_ROW_ALT   = colors.HexColor("#EEF4FB")
C_NOTEBG    = colors.HexColor("#FFF3CD")
C_NOTEBDR   = colors.HexColor("#E8A000")
C_GREY      = colors.HexColor("#555555")
C_WHITE     = colors.white
C_BLACK     = colors.black
C_FLOWBG    = colors.HexColor("#EBF4FF")

# ── paragraph styles ──────────────────────────────────────────────────────────
def S(name, **kw):
    return ParagraphStyle(name, **kw)

TITLE  = S("TITLE",  fontSize=15, leading=18, textColor=C_WHITE,
           fontName="Helvetica-Bold", alignment=TA_CENTER, spaceAfter=2)
SUBTITLE = S("SUBTITLE", fontSize=8.5, leading=10, textColor=colors.HexColor("#A8C8F0"),
             fontName="Helvetica-Oblique", alignment=TA_CENTER)
H1     = S("H1",     fontSize=11, leading=13, textColor=C_WHITE,
           fontName="Helvetica-Bold", alignment=TA_LEFT, spaceBefore=3, spaceAfter=2)
H2     = S("H2",     fontSize=10, leading=12, textColor=C_MID,
           fontName="Helvetica-Bold", alignment=TA_LEFT, spaceBefore=4, spaceAfter=1)
H3     = S("H3",     fontSize=9,  leading=11, textColor=C_DARK,
           fontName="Helvetica-Bold", alignment=TA_LEFT, spaceBefore=2, spaceAfter=1)
BODY   = S("BODY",   fontSize=9,  leading=11.5, textColor=C_BLACK,
           fontName="Helvetica",  alignment=TA_LEFT, spaceAfter=1)
BULLET = S("BULLET", fontSize=9,  leading=11.5, textColor=C_BLACK,
           fontName="Helvetica",  alignment=TA_LEFT, leftIndent=10, bulletIndent=2, spaceAfter=1)
BULLET2= S("BULLET2",fontSize=9,  leading=11.5, textColor=C_BLACK,
           fontName="Helvetica",  alignment=TA_LEFT, leftIndent=22, bulletIndent=14, spaceAfter=1)
CAPTION= S("CAPTION",fontSize=8,  leading=10, textColor=C_GREY,
           fontName="Helvetica-Oblique", alignment=TA_CENTER, spaceAfter=2)
CELL   = S("CELL",   fontSize=8.5,leading=10.5, textColor=C_BLACK,
           fontName="Helvetica",  alignment=TA_LEFT)
CELL_H = S("CELL_H", fontSize=8.5,leading=10.5, textColor=C_WHITE,
           fontName="Helvetica-Bold", alignment=TA_CENTER)
FLOW_S = S("FLOW_S", fontSize=8.5,leading=10.5, textColor=C_DARK,
           fontName="Helvetica",  alignment=TA_CENTER)
ARROW_S= S("ARROW_S",fontSize=12, leading=13, textColor=C_ACCENT,
           fontName="Helvetica-Bold", alignment=TA_CENTER)

def b(t):  return f"<b>{t}</b>"
def i(t):  return f"<i>{t}</i>"
def bi(t): return f"<b><i>{t}</i></b>"

# ── builders ──────────────────────────────────────────────────────────────────
def sec(title, emoji=""):
    label = f"{emoji}  {title}" if emoji else title
    t = Table([[Paragraph(label, H1)]], colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND', (0,0),(-1,-1), C_MID),
        ('LEFTPADDING',(0,0),(-1,-1), 6),
        ('RIGHTPADDING',(0,0),(-1,-1), 6),
        ('TOPPADDING',(0,0),(-1,-1), 4),
        ('BOTTOMPADDING',(0,0),(-1,-1), 4),
    ]))
    return t

def sub(t):  return Paragraph(t, H2)
def sub3(t): return Paragraph(t, H3)
def body(t): return Paragraph(t, BODY)

def bul(text, level=1):
    st = BULLET if level == 1 else BULLET2
    ch = "•" if level == 1 else "–"
    return Paragraph(f"{ch}  {text}", st)

def sp(h=4): return Spacer(1, h)

def tbl(headers, rows, widths=None, zebra=True):
    if widths is None:
        n = len(headers)
        widths = [CONTENT_W / n] * n
    data = [[Paragraph(h, CELL_H) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), CELL) for c in row])
    ts = [
        ('BACKGROUND',(0,0),(-1,0), C_MID),
        ('TEXTCOLOR',(0,0),(-1,0), C_WHITE),
        ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),
        ('FONTSIZE',(0,0),(-1,0), 8.5),
        ('ALIGN',(0,0),(-1,0),'CENTER'),
        ('FONTNAME',(0,1),(-1,-1),'Helvetica'),
        ('FONTSIZE',(0,1),(-1,-1), 8.5),
        ('ALIGN',(0,1),(-1,-1),'LEFT'),
        ('GRID',(0,0),(-1,-1), 0.5, colors.HexColor("#B0C8E8")),
        ('BOX',(0,0),(-1,-1), 1, C_MID),
        ('LEFTPADDING',(0,0),(-1,-1), 5),
        ('RIGHTPADDING',(0,0),(-1,-1), 5),
        ('TOPPADDING',(0,0),(-1,-1), 3),
        ('BOTTOMPADDING',(0,0),(-1,-1), 3),
        ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ]
    if zebra:
        for r in range(1, len(data)):
            if r % 2 == 0:
                ts.append(('BACKGROUND',(0,r),(-1,r), C_ROW_ALT))
    t = Table(data, colWidths=widths)
    t.setStyle(TableStyle(ts))
    return t

def flowchart(steps):
    items = []
    for idx, s in enumerate(steps):
        items.append(s)
        if idx < len(steps) - 1:
            items.append("→")
    n_s = len(steps)
    n_a = n_s - 1
    sw  = (CONTENT_W - n_a * 1.0*cm) / n_s
    cw  = []
    for idx in range(len(items)):
        cw.append(sw if idx % 2 == 0 else 1.0*cm)
    row = []
    for idx, item in enumerate(items):
        if idx % 2 == 0:
            row.append(Paragraph(item, FLOW_S))
        else:
            row.append(Paragraph(item, ARROW_S))
    t = Table([row], colWidths=cw)
    ts = [
        ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
        ('ALIGN',(0,0),(-1,-1),'CENTER'),
        ('LEFTPADDING',(0,0),(-1,-1), 4),
        ('RIGHTPADDING',(0,0),(-1,-1), 4),
        ('TOPPADDING',(0,0),(-1,-1), 5),
        ('BOTTOMPADDING',(0,0),(-1,-1), 5),
    ]
    for idx in range(0, len(items), 2):
        ts.append(('BACKGROUND',(idx,0),(idx,0), C_FLOWBG))
        ts.append(('BOX',(idx,0),(idx,0), 0.6, C_MID))
    t.setStyle(TableStyle(ts))
    return t

def note(text):
    t = Table([[Paragraph(f"📌  {text}", S("NB", fontSize=8.5, leading=10.5,
        fontName="Helvetica-Bold", textColor=C_DARK))]], colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1), C_NOTEBG),
        ('BOX',(0,0),(-1,-1), 0.8, C_NOTEBDR),
        ('LEFTPADDING',(0,0),(-1,-1), 6),
        ('RIGHTPADDING',(0,0),(-1,-1), 6),
        ('TOPPADDING',(0,0),(-1,-1), 4),
        ('BOTTOMPADDING',(0,0),(-1,-1), 4),
    ]))
    return t

def fit_img(path, max_w, max_h):
    from PIL import Image as PILImg
    pil = PILImg.open(path)
    w, h = pil.size
    r = min(max_w / w, max_h / h)
    return RLImage(path, width=w*r, height=h*r)

def footer(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 7.5)
    canvas.setFillColor(C_GREY)
    canvas.drawCentredString(PAGE_W/2, BM*0.55, "Made By Sohaib Khan  |  SMC 5")
    canvas.setStrokeColor(colors.HexColor("#CCCCCC"))
    canvas.setLineWidth(0.5)
    canvas.line(LM, BM*0.8, PAGE_W-RM, BM*0.8)
    canvas.drawRightString(PAGE_W-RM, BM*0.55, f"Page {doc.page}")
    canvas.restoreState()

# ── document ──────────────────────────────────────────────────────────────────
IMG = "/tmp/workspace/oi"
OUT = "/tmp/workspace/oi/OsteogenesisImperfecta_Notes.pdf"

doc = SimpleDocTemplate(OUT, pagesize=A4,
    leftMargin=LM, rightMargin=RM,
    topMargin=TM, bottomMargin=BM+0.8*cm,
    title="Osteogenesis Imperfecta – Structured Study Notes",
    author="Sohaib Khan SMC 5")

story = []

# ── TITLE BLOCK ───────────────────────────────────────────────────────────────
title_tbl = Table([
    [Paragraph("🦴  OSTEOGENESIS IMPERFECTA", TITLE)],
    [Paragraph("Brittle Bone Disease  |  Structured Study Notes", SUBTITLE)],
], colWidths=[CONTENT_W])
title_tbl.setStyle(TableStyle([
    ('BACKGROUND',(0,0),(-1,-1), C_DARK),
    ('LEFTPADDING',(0,0),(-1,-1), 8),
    ('RIGHTPADDING',(0,0),(-1,-1), 8),
    ('TOPPADDING',(0,0),(-1,-1), 8),
    ('BOTTOMPADDING',(0,0),(-1,-1), 8),
]))
story.append(title_tbl)
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 1  INTRODUCTION
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("1. INTRODUCTION & OVERVIEW", "📖"))
story.append(sp(3))
story.append(sub("1a. Also Known As"))
story.append(bul(bi("Brittle Bone Disease")))
story.append(bul(b("Lobstein's Disease") + " (less commonly used)"))
story.append(sp(3))
story.append(sub("1b. Clinical Importance"))
story.append(bul("Frequently tested in " + b("NEET PG exams") + " – typically " + bi("1–2 questions every cycle.")))
story.append(bul(b("Crucial to differentiate") + " from other bone disorders, especially " + bi("Marble Bone Disease.")))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 2  DIFFERENTIATION TABLE
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("2. DIFFERENTIATION: OI vs MARBLE BONE DISEASE", "🔍"))
story.append(sp(4))
diff_h = ["Feature", bi("Osteogenesis Imperfecta"), bi("Marble Bone Disease")]
diff_r = [
    [b("Bone Quality"),       "Qualitative defect in Type 1 collagen",          "Excessive bone formation"],
    [b("Bone Density"),       "Normal quantity but " + b("defective integrity"), b("Increased") + ", dense bone"],
    [b("Pathophysiology"),    "Mutation in Type 1 collagen gene (COL1A1/A2)",    "Failure of osteoclastic activity"],
    [b("Clinical Presentation"), "Multiple fractures, ligament laxity",          "Bone sclerosis, brittle but dense bone"],
]
story.append(tbl(diff_h, diff_r, widths=[4*cm, 7.5*cm, CONTENT_W-11.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 3  GENETIC & MOLECULAR BASIS
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("3. GENETIC & MOLECULAR BASIS", "🧬"))
story.append(sp(3))
story.append(bul(bi("Type 1 collagen mutation") + " is central."))
story.append(bul("Mutation occurs in " + bi("COL1A1") + " or " + bi("COL1A2") + " genes, encoding collagen type 1 alpha chains."))
story.append(bul(b("Collagen type 1") + " is critical for structural integrity in:"))
story.append(bul("Bone", level=2))
story.append(bul("Skin", level=2))
story.append(bul("Ligaments", level=2))
story.append(bul("Other connective tissues", level=2))
story.append(sp(3))
story.append(sub("3a. Inheritance Pattern"))
story.append(bul(b("Mostly " + bi("Autosomal Dominant")) + " (most common for exam focus)."))
story.append(bul("Rarely " + i("autosomal recessive") + " or " + i("non-Mendelian") + " forms exist."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 4  PATHOPHYSIOLOGY FLOWCHART
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("4. PATHOPHYSIOLOGY FLOWCHART", "🔬"))
story.append(sp(4))
story.append(flowchart([
    "COL1A1 / COL1A2\nGene Mutation",
    "Defective Type 1\nCollagen Synthesis",
    "Weak Structural\nIntegrity of Bone\n& Connective Tissue",
    "Increased Bone\nFragility",
    "Clinical\nManifestations",
]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 5  CLINICAL FEATURES
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("5. CLINICAL FEATURES", "🩺"))
story.append(sp(4))

story.append(sub("5a. Orthopaedic Manifestations"))
story.append(bul(b("Multiple fractures") + " following minor trauma – often in " + i("neonates, children, and adolescents.")))
story.append(bul("Fracture frequency " + b("decreases after adolescence") + " but " + b("rises post-menopause.")))
story.append(bul(b("Most commonly affected bones:")))
story.append(bul(bi("Lower limbs > Upper limbs"), level=2))
story.append(bul(bi("Femur > Tibia") + " > Other bones (humerus, forearm, skull)", level=2))
story.append(bul(b("Ligamentous laxity") + " leads to repeated dislocations:"))
story.append(bul(i("Hip dislocation"), level=2))
story.append(bul(i("Patellar dislocation"), level=2))
story.append(bul(i("Radial head dislocation"), level=2))
story.append(bul(bi("Wormian bones:") + " Multiple bone fragments within cranial sutures (especially " + b("lambdoid sutures.)")))
story.append(sp(4))

# Wormian bones image
img2 = fit_img(os.path.join(IMG, "img2_wormian_bones.jpg"), max_w=CONTENT_W, max_h=5.5*cm)
story.append(img2)
story.append(Paragraph("<i>Fig 1: Wormian bones in OI – multiple small accessory bones within cranial sutures on skull X-ray (arrows)</i>", CAPTION))
story.append(sp(5))

story.append(sub("5b. Non-Orthopaedic Manifestations"))
story.append(sp(2))

nonortho_h = ["System", b("Manifestation"), "Explanation"]
nonortho_r = [
    [b("Eyes"),
     bi("Blue sclera"),
     "Thin, translucent sclera reveals underlying " + i("uveal pigmentation")],
    ["",
     bi("Saturn's ring") + " (white ring around cornea)",
     "Deposits seen in corneal periphery"],
    ["",
     i("Hyperopia"),
     "Refractive error"],
    ["",
     i("Retinal detachments"),
     "Due to weakened connective tissue structure"],
    [b("Ears"),
     bi("Hearing loss") + " (conductive & sensorineural)",
     b("Conductive:") + " otosclerosis of middle ear bones; " + b("Sensorineural:") + " 8th nerve compression"],
    [b("Teeth"),
     bi("Dentogenesis imperfecta"),
     "Hypoplastic, fragile teeth, especially " + b("lower incisors") + "; enamel usually normal"],
    [b("Skin & Muscle"),
     i("Fragile skin, easy bruising"),
     "Poor collagen weakens skin integrity"],
    ["",
     i("Muscle hypertonia"),
     "Muscle–bone imbalance contributes to fractures"],
    [b("Other"),
     bi("Malignant hyperthermia") + ", heat intolerance",
     "Increased sweating and susceptibility to heat strokes"],
]
story.append(tbl(nonortho_h, nonortho_r,
    widths=[2.5*cm, 5.5*cm, CONTENT_W-8*cm]))
story.append(sp(4))

# Blue sclera image + Dentinogenesis image side by side
img1 = fit_img(os.path.join(IMG, "img1_blue_sclera.jpg"),   max_w=8.5*cm, max_h=3.5*cm)
img3 = fit_img(os.path.join(IMG, "img3_dentinogenesis.jpg"), max_w=8.5*cm, max_h=3.5*cm)

img_row = Table(
    [[img1, img3]],
    colWidths=[CONTENT_W/2, CONTENT_W/2]
)
img_row.setStyle(TableStyle([
    ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ('ALIGN',(0,0),(-1,-1),'CENTER'),
    ('LEFTPADDING',(0,0),(-1,-1), 2),
    ('RIGHTPADDING',(0,0),(-1,-1), 2),
    ('TOPPADDING',(0,0),(-1,-1), 0),
    ('BOTTOMPADDING',(0,0),(-1,-1), 0),
]))
story.append(img_row)
cap_row = Table(
    [[Paragraph("<i>Fig 2: Blue sclera – thin translucent sclera revealing uveal pigment</i>", CAPTION),
      Paragraph("<i>Fig 3: Dentinogenesis imperfecta – hypoplastic, fragile, discoloured teeth</i>", CAPTION)]],
    colWidths=[CONTENT_W/2, CONTENT_W/2]
)
cap_row.setStyle(TableStyle([
    ('LEFTPADDING',(0,0),(-1,-1), 2),
    ('RIGHTPADDING',(0,0),(-1,-1), 2),
    ('TOPPADDING',(0,0),(-1,-1), 1),
    ('BOTTOMPADDING',(0,0),(-1,-1), 0),
]))
story.append(cap_row)
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 6  DIAGNOSTIC APPROACH
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("6. DIAGNOSTIC APPROACH", "🔎"))
story.append(sp(4))

story.append(sub("6a. Genetic Diagnosis"))
story.append(bul(bi("Gold standard:") + "  Genetic analysis of " + b("skin fibroblasts.")))
story.append(bul(b("Techniques:")))
story.append(bul(i("PCR amplification"), level=2))
story.append(bul(i("Gel electrophoresis") + " to detect " + b("COL1A1 / COL1A2") + " mutations", level=2))
story.append(sp(3))

story.append(sub("6b. Radiological Diagnosis"))
story.append(bul("Presence of " + b("fractures in multiple bones") + " at " + bi("various stages of healing.")))
story.append(bul("Differential diagnosis includes " + i("child abuse") + " – genetic and clinical context distinguishes OI."))
story.append(sp(3))

story.append(sub("6c. Biochemical Markers"))
story.append(sp(2))
bio_h = ["Marker", "Observation in OI", "Notes"]
bio_r = [
    [bi("Alkaline phosphatase"), b("Mild elevation") + " due to active bone repair", "Significantly higher in osteosarcoma"],
    ["Acid phosphatase",          "No relation",                                      b("Not useful")],
]
story.append(tbl(bio_h, bio_r, widths=[4.5*cm, 6*cm, CONTENT_W-10.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 7  TREATMENT
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("7. TREATMENT MODALITIES", "💊"))
story.append(sp(4))

tx_h = ["Treatment", "Mechanism / Indication", "Notes"]
tx_r = [
    [b("Gene therapy"),
     "Attempts to replace/repair defective COL1A gene",
     "Experimental, emerging therapy"],
    [bi("Bisphosphonates"),
     "Inhibit osteoclasts, increase bone density",
     bi("Pamidronate") + " is the " + b("drug of choice") + " – reduces fracture rate"],
    [b("Surgical management"),
     "Internal fixation with rods, plates to prevent fractures",
     "Supportive and symptomatic"],
    [b("Supportive care"),
     "Pain management, physiotherapy",
     "Improves quality of life"],
]
story.append(tbl(tx_h, tx_r, widths=[4.5*cm, 7*cm, CONTENT_W-11.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 8  SUMMARY TABLE
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("8. SUMMARY – KEY HIGHLIGHTS", "📋"))
story.append(sp(4))

sum_h = ["Aspect", "Details"]
sum_r = [
    [b("Synonyms"),         bi("Brittle Bone Disease") + ", Lobstein's disease"],
    [b("Etiology"),         "Mutation in " + bi("COL1A1 / COL1A2") + " gene (Type 1 collagen)"],
    [b("Inheritance"),      "Primarily " + bi("Autosomal Dominant")],
    [b("Key Clinical Features"), "Multiple fractures, " + bi("blue sclera") + ", ligament laxity, "
                                 + bi("dentinogenesis imperfecta") + ", hearing loss"],
    [b("Diagnosis"),        "Genetic testing, radiographs showing fractures at different healing stages, "
                            "mild " + bi("alkaline phosphatase elevation")],
    [b("Treatment"),        bi("Bisphosphonates (Pamidronate)") + ", gene therapy (experimental), surgical fixation"],
]
story.append(tbl(sum_h, sum_r, widths=[4.5*cm, CONTENT_W-4.5*cm]))
story.append(sp(5))

story.append(note(
    "OI: COL1A1/COL1A2 mutation → qualitative collagen defect → fragile bones  |  "
    "Drug of choice: Pamidronate (bisphosphonate)  |  "
    "Gold standard diagnosis: Skin fibroblast genetic analysis  |  "
    "Key sign: Blue sclera + Wormian bones + Dentinogenesis imperfecta"
))

doc.build(story, onFirstPage=footer, onLaterPages=footer)
print(f"PDF written: {OUT}")

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, Image as RLImage,
)
import os

PAGE_W, PAGE_H = A4
LM = RM = 1.4 * cm
TM = BM = 1.5 * cm
CONTENT_W = PAGE_W - LM - RM

C_DARK   = colors.HexColor("#1A3A5C")
C_MID    = colors.HexColor("#1F5FA6")
C_ACCENT = colors.HexColor("#C0392B")
C_ROW    = colors.HexColor("#EEF4FB")
C_NOTEBG = colors.HexColor("#FFF3CD")
C_NOTEBDR= colors.HexColor("#E8A000")
C_GREY   = colors.HexColor("#555555")
C_WHITE  = colors.white
C_BLACK  = colors.black
C_FLOWBG = colors.HexColor("#EBF4FF")

def S(name,**kw): return ParagraphStyle(name,**kw)

TITLE  = S("T",  fontSize=15,leading=18,textColor=C_WHITE,fontName="Helvetica-Bold",alignment=TA_CENTER)
SUBT   = S("ST", fontSize=8.5,leading=10,textColor=colors.HexColor("#A8C8F0"),fontName="Helvetica-Oblique",alignment=TA_CENTER)
H1     = S("H1", fontSize=11,leading=13,textColor=C_WHITE,fontName="Helvetica-Bold",alignment=TA_LEFT,spaceBefore=3,spaceAfter=2)
H2     = S("H2", fontSize=10,leading=12,textColor=C_MID,fontName="Helvetica-Bold",alignment=TA_LEFT,spaceBefore=4,spaceAfter=1)
BODY   = S("BO", fontSize=9, leading=11.5,textColor=C_BLACK,fontName="Helvetica",alignment=TA_LEFT,spaceAfter=1)
BUL    = S("BL", fontSize=9, leading=11.5,textColor=C_BLACK,fontName="Helvetica",alignment=TA_LEFT,leftIndent=10,bulletIndent=2,spaceAfter=1)
BUL2   = S("B2", fontSize=9, leading=11.5,textColor=C_BLACK,fontName="Helvetica",alignment=TA_LEFT,leftIndent=22,bulletIndent=14,spaceAfter=1)
CAP    = S("CP", fontSize=8, leading=10,textColor=C_GREY,fontName="Helvetica-Oblique",alignment=TA_CENTER,spaceAfter=2)
CELL   = S("CE", fontSize=8.5,leading=10.5,textColor=C_BLACK,fontName="Helvetica",alignment=TA_LEFT)
CELL_H = S("CH", fontSize=8.5,leading=10.5,textColor=C_WHITE,fontName="Helvetica-Bold",alignment=TA_CENTER)
FLOW_S = S("FS", fontSize=8.5,leading=10.5,textColor=C_DARK,fontName="Helvetica",alignment=TA_CENTER)
ARRS   = S("AS", fontSize=12,leading=13,textColor=C_ACCENT,fontName="Helvetica-Bold",alignment=TA_CENTER)

def b(t):  return f"<b>{t}</b>"
def i(t):  return f"<i>{t}</i>"
def bi(t): return f"<b><i>{t}</i></b>"

def sec(title, emoji=""):
    lbl = f"{emoji}  {title}" if emoji else title
    t = Table([[Paragraph(lbl,H1)]],colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1),C_MID),
        ('LEFTPADDING',(0,0),(-1,-1),6),('RIGHTPADDING',(0,0),(-1,-1),6),
        ('TOPPADDING',(0,0),(-1,-1),4),('BOTTOMPADDING',(0,0),(-1,-1),4),
    ]))
    return t

def sub(t): return Paragraph(t,H2)
def bul(text,level=1):
    st = BUL if level==1 else BUL2
    ch = "•" if level==1 else "–"
    return Paragraph(f"{ch}  {text}",st)
def sp(h=4): return Spacer(1,h)

def tbl(headers,rows,widths=None,zebra=True):
    if widths is None:
        n=len(headers); widths=[CONTENT_W/n]*n
    data=[[Paragraph(h,CELL_H) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c),CELL) for c in row])
    ts=[
        ('BACKGROUND',(0,0),(-1,0),C_MID),('TEXTCOLOR',(0,0),(-1,0),C_WHITE),
        ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),('FONTSIZE',(0,0),(-1,0),8.5),
        ('ALIGN',(0,0),(-1,0),'CENTER'),
        ('FONTNAME',(0,1),(-1,-1),'Helvetica'),('FONTSIZE',(0,1),(-1,-1),8.5),
        ('ALIGN',(0,1),(-1,-1),'LEFT'),
        ('GRID',(0,0),(-1,-1),0.5,colors.HexColor("#B0C8E8")),
        ('BOX',(0,0),(-1,-1),1,C_MID),
        ('LEFTPADDING',(0,0),(-1,-1),5),('RIGHTPADDING',(0,0),(-1,-1),5),
        ('TOPPADDING',(0,0),(-1,-1),3),('BOTTOMPADDING',(0,0),(-1,-1),3),
        ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ]
    if zebra:
        for r in range(1,len(data)):
            if r%2==0: ts.append(('BACKGROUND',(0,r),(-1,r),C_ROW))
    t=Table(data,colWidths=widths)
    t.setStyle(TableStyle(ts))
    return t

def flowchart(steps):
    items=[]
    for idx,s in enumerate(steps):
        items.append(s)
        if idx<len(steps)-1: items.append("→")
    n_s=len(steps); n_a=n_s-1
    sw=(CONTENT_W-n_a*1.0*cm)/n_s
    cw=[sw if idx%2==0 else 1.0*cm for idx in range(len(items))]
    row=[]
    for idx,item in enumerate(items):
        if idx%2==0: row.append(Paragraph(item,FLOW_S))
        else: row.append(Paragraph(item,ARRS))
    t=Table([row],colWidths=cw)
    ts=[
        ('VALIGN',(0,0),(-1,-1),'MIDDLE'),('ALIGN',(0,0),(-1,-1),'CENTER'),
        ('LEFTPADDING',(0,0),(-1,-1),4),('RIGHTPADDING',(0,0),(-1,-1),4),
        ('TOPPADDING',(0,0),(-1,-1),5),('BOTTOMPADDING',(0,0),(-1,-1),5),
    ]
    for idx in range(0,len(items),2):
        ts.append(('BACKGROUND',(idx,0),(idx,0),C_FLOWBG))
        ts.append(('BOX',(idx,0),(idx,0),0.6,C_MID))
    t.setStyle(TableStyle(ts))
    return t

def note(text):
    t=Table([[Paragraph(f"📌  {text}",S("NB",fontSize=8.5,leading=10.5,
        fontName="Helvetica-Bold",textColor=C_DARK))]],colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1),C_NOTEBG),('BOX',(0,0),(-1,-1),0.8,C_NOTEBDR),
        ('LEFTPADDING',(0,0),(-1,-1),6),('RIGHTPADDING',(0,0),(-1,-1),6),
        ('TOPPADDING',(0,0),(-1,-1),4),('BOTTOMPADDING',(0,0),(-1,-1),4),
    ]))
    return t

def fit_img(path,max_w,max_h):
    from PIL import Image as P
    pil=P.open(path)
    w,h=pil.size
    r=min(max_w/w,max_h/h)
    return RLImage(path,width=w*r,height=h*r)

def side_by_side(left_items, right_img, right_w=6.5*cm):
    lw = CONTENT_W - right_w - 0.3*cm
    t = Table([[left_items, right_img]], colWidths=[lw, right_w])
    t.setStyle(TableStyle([
        ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
        ('LEFTPADDING',(0,0),(-1,-1),0),('RIGHTPADDING',(0,0),(-1,-1),0),
        ('TOPPADDING',(0,0),(-1,-1),0),('BOTTOMPADDING',(0,0),(-1,-1),0),
    ]))
    return t

def footer(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica",7.5)
    canvas.setFillColor(C_GREY)
    canvas.drawCentredString(PAGE_W/2,BM*0.55,"Made By Sohaib Khan  |  SMC 5")
    canvas.setStrokeColor(colors.HexColor("#CCCCCC"))
    canvas.setLineWidth(0.5)
    canvas.line(LM,BM*0.8,PAGE_W-RM,BM*0.8)
    canvas.drawRightString(PAGE_W-RM,BM*0.55,f"Page {doc.page}")
    canvas.restoreState()

# ─────────────────────────────────────────────────────────────────────────────
IMG = "/tmp/workspace/paget"
OUT = "/tmp/workspace/paget/PagetDisease_Notes.pdf"

doc = SimpleDocTemplate(OUT, pagesize=A4,
    leftMargin=LM, rightMargin=RM,
    topMargin=TM, bottomMargin=BM+0.8*cm,
    title="Paget Disease of Bone – Structured Study Notes",
    author="Sohaib Khan SMC 5")

story=[]

# ── TITLE ─────────────────────────────────────────────────────────────────────
ttbl=Table([
    [Paragraph("🦴  PAGET DISEASE OF BONE",TITLE)],
    [Paragraph("Osteitis Deformans  |  Structured Study Notes  |  Orthopaedics",SUBT)],
],colWidths=[CONTENT_W])
ttbl.setStyle(TableStyle([
    ('BACKGROUND',(0,0),(-1,-1),C_DARK),
    ('LEFTPADDING',(0,0),(-1,-1),8),('RIGHTPADDING',(0,0),(-1,-1),8),
    ('TOPPADDING',(0,0),(-1,-1),8),('BOTTOMPADDING',(0,0),(-1,-1),8),
]))
story.append(ttbl); story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 1 – INTRODUCTION
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("1. INTRODUCTION & OVERVIEW","📖"))
story.append(sp(3))
story.append(sub("1a. Also Known As"))
story.append(bul(bi("Osteitis Deformans")))
story.append(bul("Named after Sir James Paget (1877)."))
story.append(sp(3))
story.append(sub("1b. Definition"))
story.append(bul("A " + bi("chronic, localized disorder of bone remodelling") + " in adults."))
story.append(bul("Characterised by " + b("accelerated, disorganised bone turnover") + " in one or more skeletal sites."))
story.append(bul("Results in " + b("enlarged, deformed, structurally weak") + " bone despite increased bone mass."))
story.append(sp(3))
story.append(sub("1c. Epidemiology"))
story.append(bul(b("Second most common") + " metabolic bone disease after osteoporosis."))
story.append(bul("Affects " + b("adults > 40 years") + "; rare below 40."))
story.append(bul(bi("Males > Females") + " (M:F = 2:1)."))
story.append(bul("More prevalent in " + i("UK, Australia, New Zealand, North America, Western Europe.") + " Rare in Asia, Africa."))
story.append(bul("Often " + b("asymptomatic") + " – discovered incidentally on X-ray or raised ALP."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 2 – AETIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("2. AETIOLOGY & GENETIC BASIS","🧬"))
story.append(sp(3))
story.append(sub("2a. Aetiology (Multifactorial)"))
story.append(bul(b("Genetic (hereditary) component:") + " ~15–30% have a " + bi("positive family history.")))
story.append(bul("Mutation in " + bi("SQSTM1 gene") + " (Sequestosome-1 / p62 protein) – most important identified mutation."))
story.append(bul("SQSTM1 encodes " + i("p62 protein") + " involved in the " + b("NF-κB signalling pathway") + " of osteoclasts."))
story.append(bul(b("Viral aetiology hypothesis:") + " Slow viral infection by " + bi("Paramyxovirus")
               + " (measles, respiratory syncytial virus, canine distemper virus) – controversial, not confirmed."))
story.append(bul("Inheritance: " + bi("Autosomal dominant") + " with variable penetrance."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 3 – PATHOPHYSIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("3. PATHOPHYSIOLOGY","🔬"))
story.append(sp(3))
story.append(sub("3a. Three Phases of Paget Disease"))
story.append(sp(2))
phase_h=["Phase","Key Process","Radiological Correlate"]
phase_r=[
    [bi("Phase 1 – Osteolytic\n(Hot Phase)"),
     b("Excessive osteoclastic resorption") + " – abnormally large, multinucleated osteoclasts with " + b(">20 nuclei per cell"),
     bi("Osteoporosis circumscripta") + " (skull); " + bi("Blade of Grass / Flame sign") + " (long bones)"],
    [bi("Phase 2 – Mixed\n(Active)"),
     "Simultaneous " + b("osteoclast + osteoblast") + " activity; haphazard bone deposition",
     b("Mixed lytic & sclerotic") + " pattern on X-ray"],
    [bi("Phase 3 – Osteosclerotic\n(Burnt-Out / Cold)"),
     b("Predominant osteoblast activity") + "; dense but structurally disorganised bone",
     bi("Cotton wool appearance") + " (skull); " + bi("Picture-frame vertebra") + "; bone enlargement"],
]
story.append(tbl(phase_h,phase_r,widths=[3.8*cm,8*cm,CONTENT_W-11.8*cm]))
story.append(sp(4))

story.append(sub("3b. Pathophysiology Flowchart"))
story.append(sp(3))
story.append(flowchart([
    "SQSTM1\nMutation\n(NF-κB ↑)",
    "Abnormal Giant\nOsteoclast\nActivation",
    "Excessive\nBone\nResorption",
    "Disorganised\nOsteoblast\nResponse",
    "Mosaic /\nWoven Bone\n(Structurally Weak)",
    "Deformity,\nFractures,\nComplications",
]))
story.append(sp(4))

story.append(sub("3c. Key Histological Feature"))
story.append(bul(bi("Mosaic pattern") + " of bone: cement lines form a " + b("jigsaw puzzle") + " appearance due to repeated cycles of resorption and deposition."))
story.append(bul("Abnormal osteoclasts: " + b("very large, multinucleated") + " (up to 100 nuclei), compared to normal 3–5 nuclei."))
story.append(bul("Woven bone replaces lamellar bone → " + b("structurally inferior") + " bone despite increased mass."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 4 – BONES COMMONLY INVOLVED
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("4. BONES COMMONLY INVOLVED","🦴"))
story.append(sp(4))
bones_h=["Bone / Site","Frequency","Key Clinical / Radiological Sign"]
bones_r=[
    [bi("Pelvis"),    b("Most common") + " (~70%)", "Enlarged, sclerotic pelvis; picture-frame ilium"],
    [bi("Lumbar Spine"), "~50%",                   bi("Picture-frame vertebra") + "; enlarged vertebral body"],
    [bi("Skull"),     "~25–40%",                   bi("Cotton wool") + " appearance; " + i("osteoporosis circumscripta") + " (early); frontal bossing; hearing loss"],
    [bi("Femur"),     "~25%",                       bi("Bowing") + " – lateral bowing; blade of grass sign"],
    [bi("Tibia"),     "~20%",                       bi("Anterior bowing") + " (sabre tibia); medial tibial stress fractures"],
    [i("Humerus, clavicle"), "Less common",         "Enlargement, cortical thickening"],
]
story.append(tbl(bones_h,bones_r,widths=[4*cm,3*cm,CONTENT_W-7*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 5 – CLINICAL FEATURES
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("5. CLINICAL FEATURES","🩺"))
story.append(sp(3))
story.append(sub("5a. Symptoms"))
story.append(bul(b("Often asymptomatic") + " – incidental discovery (raised ALP, abnormal X-ray)."))
story.append(bul(bi("Bone pain:") + " Deep, aching, " + b("worse at rest and at night") + " (unlike OA which improves at rest)."))
story.append(bul(bi("Bone deformity:") + " Bowing of long bones, skull enlargement, spinal kyphosis."))
story.append(bul(bi("Pathological fractures:") + " Due to structurally weak bone – " + b("chalk-stick / banana fractures") + " in long bones."))
story.append(bul("Fractures " + b("most common in femur") + " > tibia > humerus."))
story.append(sp(3))
story.append(sub("5b. Skull Involvement"))

img1 = fit_img(os.path.join(IMG,"img1_cotton_wool.jpg"), max_w=7*cm, max_h=5.5*cm)
skull_left = [
    bul(bi("Frontal bossing") + " – enlargement of the frontal bone."),
    sp(2),
    bul(b("Increased hat size") + " – classical history."),
    sp(2),
    bul(bi("Hearing loss") + " (most common neurological complication):"),
    bul(b("Conductive:") + " narrowing of external auditory canal / ossicular involvement.", level=2),
    bul(b("Sensorineural:") + " 8th cranial nerve compression at skull base.", level=2),
    sp(2),
    bul(bi("Basilar invagination") + " (platybasia) – softened skull base telescopes into cranium → " + b("brain stem compression.")),
    sp(2),
    bul(bi("Lion face") + " (leontiasis ossea) – severe facial involvement."),
]
story.append(side_by_side(skull_left, img1, right_w=7.2*cm))
story.append(Paragraph("<i>Fig 1: Cotton wool appearance on skull X-ray – areas of osteosclerosis on dense skull (Paget disease)</i>", CAP))
story.append(sp(4))

story.append(sub("5c. Long Bone & Spine Involvement"))
img2 = fit_img(os.path.join(IMG,"img2_tibia_xray.jpg"), max_w=5*cm, max_h=6.5*cm)
img3 = fit_img(os.path.join(IMG,"img3_flame_sign.jpg"), max_w=5*cm, max_h=5*cm)

bone_left = [
    bul(bi("Anterior bowing of tibia") + " (" + i("sabre tibia") + ") – hallmark of tibial Paget."),
    sp(2),
    bul(bi("Lateral bowing of femur") + "."),
    sp(2),
    bul(bi("Blade of grass / Flame sign") + " on X-ray:"),
    bul("V-shaped lytic advancing front in long bone diaphysis.", level=2),
    bul("Seen in the " + b("osteolytic phase."), level=2),
    sp(2),
    bul(bi("Picture-frame vertebra") + " – cortical thickening of all 4 vertebral margins with central radiolucency."),
    sp(2),
    bul(bi("Ivory vertebra") + " – uniformly dense vertebral body (sclerotic phase)."),
]
imgs_row = Table([[img2, sp(4), img3]], colWidths=[5.2*cm, 0.5*cm, 5.2*cm])
imgs_row.setStyle(TableStyle([
    ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ('LEFTPADDING',(0,0),(-1,-1),0),('RIGHTPADDING',(0,0),(-1,-1),0),
    ('TOPPADDING',(0,0),(-1,-1),0),('BOTTOMPADDING',(0,0),(-1,-1),0),
]))
rw = CONTENT_W - 5.2*cm - 5.2*cm - 0.5*cm - 0.4*cm
bone_layout = Table([[bone_left, imgs_row]], colWidths=[rw, 10.9*cm])
bone_layout.setStyle(TableStyle([
    ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ('LEFTPADDING',(0,0),(-1,-1),0),('RIGHTPADDING',(0,0),(-1,-1),0),
    ('TOPPADDING',(0,0),(-1,-1),0),('BOTTOMPADDING',(0,0),(-1,-1),0),
]))
story.append(bone_layout)
story.append(Paragraph(
    "<i>Fig 2: Bowing tibia X-ray (Paget)   |   Fig 3: Blade of grass / Flame sign – V-shaped lytic front in long bone</i>", CAP))
story.append(sp(4))

story.append(sub("5d. Vascular & Other Manifestations"))
story.append(bul(bi("High-output cardiac failure:") + " Markedly " + b("increased blood flow") + " to pagetic bone (hypervascular) → "
                + b("arteriovenous shunting") + " → increased cardiac output → high-output CCF."))
story.append(bul("Skin over pagetic bone may be " + b("warm") + " (increased vascularity)."))
story.append(bul(bi("Spinal stenosis:") + " Enlarged vertebrae compress spinal cord and nerve roots."))
story.append(bul(bi("Cranial nerve palsies:") + " CN VIII (most common), CN II, CN VII due to foraminal narrowing."))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 6 – NON-ORTHOPAEDIC MANIFESTATIONS TABLE
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("6. SYSTEMIC MANIFESTATIONS","⚕️"))
story.append(sp(3))
sys_h=["System","Manifestation","Mechanism"]
sys_r=[
    [b("Cardiovascular"),
     bi("High-output cardiac failure"),
     "Hypervascular pagetic bone → AV shunting → ↑ cardiac output"],
    [b("Neurological"),
     bi("Hearing loss") + " (CN VIII most common)",
     "Conductive: canal narrowing; Sensorineural: CN VIII compression"],
    ["",
     "Cranial nerve palsies (CN II, VII, VIII)",
     "Foraminal narrowing by sclerotic bone"],
    ["",
     bi("Basilar invagination") + " → brainstem compression",
     "Softened skull base collapses inward"],
    ["",
     i("Spinal stenosis, radiculopathy, myelopathy"),
     "Enlarged vertebrae compress neural structures"],
    [b("Oncological"),
     bi("Osteosarcoma") + " (most feared complication)",
     "Malignant transformation of pagetic bone (~1% lifetime risk); " + b("ALP markedly elevated")],
    ["",
     i("Giant cell tumour"),
     "Less common malignant transformation"],
    [b("Metabolic"),
     i("Hypercalcaemia") + " (if immobilised)",
     "Immobility + high bone turnover releases Ca²⁺"],
    ["",
     i("Hyperuricaemia / gout"),
     "Increased nucleic acid turnover from high cell activity"],
]
story.append(tbl(sys_h,sys_r,widths=[3*cm,5.5*cm,CONTENT_W-8.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 7 – INVESTIGATIONS
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("7. INVESTIGATIONS & DIAGNOSIS","🔎"))
story.append(sp(3))
story.append(sub("7a. Biochemical Markers"))
story.append(sp(2))
bio_h=["Marker","Finding in Paget","Notes"]
bio_r=[
    [bi("Serum Alkaline Phosphatase (ALP)"),
     b("Markedly elevated") + " (best single marker)",
     b("Most reliable") + " marker for diagnosis and monitoring therapy"],
    [i("Urinary hydroxyproline"),
     b("Elevated") + " (reflects bone resorption)",
     "Less specific; now largely replaced by newer markers"],
    [i("Serum osteocalcin"),
     "Elevated",
     "Marker of osteoblast activity"],
    [i("Urinary N-telopeptide / CTX"),
     "Elevated",
     "Specific bone resorption markers"],
    [i("Serum calcium & phosphate"),
     b("Usually normal"),
     "Raised Ca²⁺ only with immobilisation"],
    [i("PTH"),
     "Normal",
     "Distinguishes from hyperparathyroidism"],
]
story.append(tbl(bio_h,bio_r,widths=[5*cm,5*cm,CONTENT_W-10*cm]))
story.append(sp(4))

story.append(sub("7b. Radiological Features Summary"))
story.append(sp(2))
rad_h=["Sign / Feature","Description","Phase / Site"]
rad_r=[
    [bi("Cotton wool appearance"),
     "Patchy osteosclerosis with ill-defined densities",
     b("Sclerotic phase") + " – Skull"],
    [bi("Osteoporosis circumscripta"),
     "Well-defined osteolysis of the skull",
     b("Osteolytic phase") + " – Skull"],
    [bi("Blade of grass / Flame sign"),
     "V-shaped lytic advancing front from articular end",
     b("Osteolytic phase") + " – Long bones"],
    [bi("Picture-frame vertebra"),
     "Cortical thickening of all 4 vertebral borders",
     "Mixed/sclerotic – Spine"],
    [bi("Ivory vertebra"),
     "Uniformly dense vertebral body",
     "Sclerotic phase – Spine"],
    [bi("Bowing of long bones"),
     "Anterior (tibia), lateral (femur)",
     "Advanced disease"],
    [bi("Enlarged bone / cortical thickening"),
     "Bone wider than normal, cortex thickened",
     "All phases"],
    [bi("Chalk-stick / Banana fracture"),
     "Transverse fracture of bowed long bone; incomplete fissure fractures on convex cortex",
     "Pathological – Long bones"],
]
story.append(tbl(rad_h,rad_r,widths=[5*cm,6.5*cm,CONTENT_W-11.5*cm]))
story.append(sp(4))

story.append(sub("7c. Bone Scan (Isotope Scintigraphy)"))
story.append(bul(b("Best investigation to assess") + " the " + bi("extent") + " and " + bi("distribution") + " of pagetic involvement across the whole skeleton."))
story.append(bul("Shows " + b("hot spots") + " (increased uptake) at sites of active disease."))
story.append(bul("Used for " + b("staging") + " and monitoring treatment response."))
story.append(sp(4))

story.append(sub("7d. Histological Findings"))
story.append(bul(bi("Mosaic pattern") + " of cement lines – pathognomonic of Paget disease."))
story.append(bul("Abnormally " + b("large multinucleated osteoclasts") + " (up to 100 nuclei)."))
story.append(bul(b("Woven bone") + " replacing normal lamellar bone."))
story.append(sp(6))

# Mosaic histology image
img4 = fit_img(os.path.join(IMG,"img4_mosaic.jpg"), max_w=6.5*cm, max_h=7*cm)
hist_left=[
    Paragraph(b("Histological Appearance:"), S("HL",fontSize=9,leading=11,fontName="Helvetica-Bold",textColor=C_MID)),
    sp(3),
    bul(bi("Mosaic bone pattern") + " with irregular cement lines resembling a jigsaw puzzle."),
    sp(2),
    bul("Reflects " + b("repeated episodes") + " of disorganised bone resorption and deposition."),
    sp(2),
    bul("Giant " + b("multinucleated osteoclasts") + " with up to 100 nuclei."),
    sp(2),
    bul(b("Increased vascularity") + " of bone marrow."),
]
hist_layout=Table([[hist_left,img4]],colWidths=[CONTENT_W-7*cm,7*cm])
hist_layout.setStyle(TableStyle([
    ('VALIGN',(0,0),(-1,-1),'MIDDLE'),
    ('LEFTPADDING',(0,0),(-1,-1),0),('RIGHTPADDING',(0,0),(-1,-1),0),
    ('TOPPADDING',(0,0),(-1,-1),0),('BOTTOMPADDING',(0,0),(-1,-1),0),
]))
story.append(hist_layout)
story.append(Paragraph("<i>Fig 4: Mosaic / jigsaw cement line pattern on histology – pathognomonic of Paget disease</i>",CAP))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 8 – TREATMENT
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("8. TREATMENT MODALITIES","💊"))
story.append(sp(4))
story.append(sub("8a. Indications for Treatment"))
story.append(bul("Bone pain attributable to Paget disease."))
story.append(bul("Preparation for " + b("orthopaedic surgery") + " on pagetic bone (reduces vascularity and blood loss)."))
story.append(bul("Neurological complications (hearing loss, spinal stenosis)."))
story.append(bul("Hypercalcaemia due to immobilisation."))
story.append(bul("Skull, spine, or weight-bearing bone involvement to prevent deformity/fracture."))
story.append(bul(b("Asymptomatic disease:") + " treatment may be considered if ALP markedly elevated or bone at risk."))
story.append(sp(3))

tx_h=["Treatment","Mechanism / Indication","Notes"]
tx_r=[
    [bi("Bisphosphonates\n(Drug of Choice)"),
     b("Inhibit osteoclast activity") + " → reduce excessive bone resorption → normalise ALP",
     bi("Zoledronic acid") + " (single IV infusion) = " + b("most potent & preferred") + "; "
     + i("Pamidronate") + " (IV), " + i("Alendronate, Risedronate") + " (oral)"],
    [bi("Calcitonin"),
     "Inhibits osteoclasts; alternative if bisphosphonates contraindicated or poorly tolerated",
     b("Salmon calcitonin") + " used; SC/IM injection; largely replaced by bisphosphonates"],
    [bi("Mithramycin\n(Plicamycin)"),
     "Cytotoxic antibiotic; inhibits osteoclast RNA synthesis",
     "Reserved for " + b("severe, refractory cases") + " or malignant transformation; significant toxicity"],
    [b("NSAIDs / Analgesics"),
     "Symptomatic pain relief",
     "Adjunct therapy only"],
    [b("Surgical Management"),
     "Fracture fixation; joint replacement (hip/knee); spinal decompression; osteotomy for bowing",
     b("Preoperative bisphosphonates") + " given to reduce pagetic vascularity and operative blood loss"],
]
story.append(tbl(tx_h,tx_r,widths=[4*cm,6.5*cm,CONTENT_W-10.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 9 – COMPLICATIONS
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("9. COMPLICATIONS","⚠️"))
story.append(sp(4))
comp_h=["Complication","Details","Key Feature"]
comp_r=[
    [bi("Osteosarcoma"),
     "Most feared; ~1% lifetime risk; suspect if " + b("sudden worsening of pain") + " + markedly ↑ ALP",
     b("Poor prognosis") + "; elderly onset sarcoma"],
    [bi("Pathological fractures"),
     b("Chalk-stick / banana fractures") + " in weight-bearing bones",
     "Femur most common"],
    [bi("High-output cardiac failure"),
     "Hypervascular pagetic bone → AV shunting → ↑ cardiac output",
     "Especially with > 30% skeletal involvement"],
    [bi("Basilar invagination"),
     "Softened skull base telescopes into cranium",
     "Brainstem + lower CN compression"],
    [bi("Deafness"),
     b("CN VIII compression") + " or ossicular involvement",
     "Most common neurological complication"],
    [bi("Spinal stenosis"),
     "Enlarged vertebrae → canal narrowing",
     "Myelopathy / radiculopathy"],
    [i("Hypercalcaemia"),
     "During immobilisation",
     "Treat underlying disease + hydration"],
    [i("Hyperuricaemia / Gout"),
     "Increased cell turnover → uric acid ↑",
     "Manage with allopurinol"],
]
story.append(tbl(comp_h,comp_r,widths=[4*cm,7.5*cm,CONTENT_W-11.5*cm]))
story.append(sp(6))

# ══════════════════════════════════════════════════════════════════════════════
# SEC 10 – SUMMARY
# ══════════════════════════════════════════════════════════════════════════════
story.append(sec("10. KEY SUMMARY","📋"))
story.append(sp(4))
sum_h=["Aspect","Details"]
sum_r=[
    [b("Synonyms"),          bi("Osteitis Deformans")],
    [b("Definition"),        "Chronic localised disorder of " + bi("accelerated, disorganised bone remodelling") + " in adults"],
    [b("Aetiology"),         bi("SQSTM1 gene mutation") + " (NF-κB pathway); viral hypothesis (" + i("Paramyxovirus") + ")"],
    [b("Inheritance"),       bi("Autosomal dominant") + " (variable penetrance); sporadic cases common"],
    [b("Epidemiology"),      "Adults > 40 yrs; " + b("M > F (2:1)") + "; commonest in UK/Australia"],
    [b("Phase 1 (Lytic)"),   bi("Osteoclast predominant") + "; " + i("osteoporosis circumscripta") + " (skull); " + i("blade of grass") + " sign (long bone)"],
    [b("Phase 2 (Mixed)"),   "Osteoclast + osteoblast activity; mixed lytic-sclerotic"],
    [b("Phase 3 (Sclerotic)"), bi("Osteoblast predominant") + "; " + i("cotton wool") + " (skull); " + i("picture-frame vertebra") + "; " + i("ivory vertebra")],
    [b("Histology"),         bi("Mosaic pattern") + " – cement lines; giant multinucleated osteoclasts (up to 100 nuclei)"],
    [b("Best Marker"),       bi("Serum ALP") + " (markedly elevated; best for diagnosis + monitoring)"],
    [b("Extent Assessment"), bi("Bone scan") + " (isotope scintigraphy) – whole-body distribution"],
    [b("Drug of Choice"),    bi("Bisphosphonates") + " – " + bi("Zoledronic acid") + " (single IV infusion, most potent)"],
    [b("Feared Complication"), bi("Osteosarcoma") + " (~1%); suspect with sudden pain + markedly ↑ ALP"],
    [b("Most Common Comp."), bi("Hearing loss") + " (CN VIII – conductive or sensorineural)"],
    [b("Bones Involved"),    "Pelvis (most common) > Lumbar spine > Skull > Femur > Tibia"],
]
story.append(tbl(sum_h,sum_r,widths=[4.5*cm,CONTENT_W-4.5*cm]))
story.append(sp(5))

story.append(note(
    "Drug of choice: Zoledronic acid (bisphosphonate)  |  "
    "Best marker: Serum ALP  |  "
    "Best for extent: Bone scan  |  "
    "Most feared complication: Osteosarcoma  |  "
    "Most common complication: Hearing loss (CN VIII)  |  "
    "Pathognomonic histology: Mosaic / jigsaw cement line pattern  |  "
    "Radiology: Cotton wool (skull), Blade of grass (long bone), Picture-frame (vertebra)"
))

doc.build(story, onFirstPage=footer, onLaterPages=footer)
print(f"PDF written: {OUT}")