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

OUTPUT = "/home/daytona/workspace/jaundice-pdf/Jaundice_Pathology.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=2*cm,
    leftMargin=2*cm,
    topMargin=2.5*cm,
    bottomMargin=2*cm,
    title="Jaundice – Pathology",
    author="Orris Medical Library",
)

# ── Color palette ────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3C5E")
MED_BLUE    = colors.HexColor("#2B6CB0")
LIGHT_BLUE  = colors.HexColor("#EBF4FF")
ACCENT      = colors.HexColor("#C05621")
TABLE_HDR   = colors.HexColor("#2B6CB0")
TABLE_ALT   = colors.HexColor("#EBF8FF")
BORDER_GREY = colors.HexColor("#CBD5E0")
WHITE       = colors.white
TEXT_DARK   = colors.HexColor("#1A202C")

# ── Styles ───────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def style(name, parent="Normal", **kw):
    s = ParagraphStyle(name, parent=base[parent], **kw)
    return s

Title_S   = style("Title_S",   "Normal",    fontSize=28, textColor=WHITE,       alignment=TA_CENTER, fontName="Helvetica-Bold", leading=34)
Sub_S     = style("Sub_S",     "Normal",    fontSize=13, textColor=colors.HexColor("#BEE3F8"), alignment=TA_CENTER, fontName="Helvetica", leading=18)
H1        = style("H1",        "Normal",    fontSize=16, textColor=WHITE,        fontName="Helvetica-Bold", leading=20, spaceBefore=6)
H2        = style("H2",        "Normal",    fontSize=13, textColor=DARK_BLUE,    fontName="Helvetica-Bold", leading=17, spaceBefore=10, spaceAfter=4)
H3        = style("H3",        "Normal",    fontSize=11, textColor=MED_BLUE,     fontName="Helvetica-Bold", leading=15, spaceBefore=8, spaceAfter=3)
Body      = style("Body",      "Normal",    fontSize=10, textColor=TEXT_DARK,    fontName="Helvetica",      leading=15, spaceBefore=3, spaceAfter=3, alignment=TA_JUSTIFY)
Bullet    = style("Bullet",    "Normal",    fontSize=10, textColor=TEXT_DARK,    fontName="Helvetica",      leading=14, leftIndent=16, spaceBefore=2)
Caption   = style("Caption",   "Normal",    fontSize=8.5, textColor=colors.HexColor("#4A5568"), fontName="Helvetica-Oblique", alignment=TA_CENTER, leading=12)
KeyBox    = style("KeyBox",    "Normal",    fontSize=10, textColor=DARK_BLUE,    fontName="Helvetica",      leading=14, leftIndent=8, spaceBefore=2)
Ref       = style("Ref",       "Normal",    fontSize=8,  textColor=colors.HexColor("#718096"), fontName="Helvetica-Oblique", leading=11)

def bullet(txt, level=0):
    indent = 16 + level*14
    s = ParagraphStyle(f"bul_{level}", parent=base["Normal"],
                       fontSize=10, textColor=TEXT_DARK, fontName="Helvetica",
                       leading=14, leftIndent=indent, firstLineIndent=-10,
                       spaceBefore=2)
    return Paragraph(f"\u2022  {txt}", s)

def hr(color=BORDER_GREY, width=1):
    return HRFlowable(width="100%", thickness=width, color=color, spaceAfter=4, spaceBefore=4)

def section_header(title, color=MED_BLUE):
    data = [[Paragraph(title, H1)]]
    t = Table(data, colWidths=["100%"])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",    (0,0),(-1,-1), 7),
        ("BOTTOMPADDING", (0,0),(-1,-1), 7),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def info_box(title, items, bg=LIGHT_BLUE, border=MED_BLUE):
    rows = [[Paragraph(f"<b>{title}</b>", H3)]]
    for item in items:
        rows.append([Paragraph(f"\u2022  {item}", KeyBox)])
    t = Table(rows, colWidths=["100%"])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX",        (0,0), (-1,-1), 1.2, border),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("RIGHTPADDING",  (0,0), (-1,-1), 10),
    ]))
    return t

def make_table(header, rows, col_widths=None):
    data = [[Paragraph(h, style("TH","Normal", fontSize=9.5, textColor=WHITE,
                                fontName="Helvetica-Bold", leading=13)) for h in header]]
    for i, row in enumerate(rows):
        bg = TABLE_ALT if i % 2 == 0 else WHITE
        data.append([Paragraph(str(c), style("TD","Normal", fontSize=9.5,
                               textColor=TEXT_DARK, fontName="Helvetica",
                               leading=13)) for c in row])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    ts = TableStyle([
        ("BACKGROUND",    (0,0), (-1,0), TABLE_HDR),
        ("GRID",          (0,0), (-1,-1), 0.5, BORDER_GREY),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [TABLE_ALT, WHITE]),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("RIGHTPADDING",  (0,0), (-1,-1), 6),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ])
    t.setStyle(ts)
    return t

# ─────────────────────────────────────────────────────────────────────────────
# BUILD STORY
# ─────────────────────────────────────────────────────────────────────────────
story = []

# ── COVER PAGE ───────────────────────────────────────────────────────────────
cover_data = [[Paragraph("JAUNDICE", Title_S)],
              [Paragraph("A Comprehensive Pathology Review", Sub_S)],
              [Spacer(1, 0.3*cm)],
              [Paragraph("Harrison's Principles of Internal Medicine (22e, 2025) &amp;<br/>Sleisenger &amp; Fordtran's Gastrointestinal and Liver Disease", Sub_S)],
              [Spacer(1, 0.3*cm)],
              [Paragraph("Orris Medical Library  |  June 2026", Sub_S)],
]
cover = Table(cover_data, colWidths=["100%"])
cover.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 14),
    ("BOTTOMPADDING", (0,0), (-1,-1), 14),
    ("LEFTPADDING",   (0,0), (-1,-1), 20),
    ("RIGHTPADDING",  (0,0), (-1,-1), 20),
]))
story.append(cover)
story.append(Spacer(1, 1.2*cm))

# short definition box
story.append(info_box(
    "Definition",
    [
        "Jaundice (icterus) is the yellowish discolouration of sclera, skin, and mucous membranes caused by deposition of bilirubin when serum bilirubin exceeds ~34 µmol/L (2 mg/dL).",
        "Clinically detectable jaundice typically appears when serum bilirubin > 2–3 mg/dL.",
        "Normal serum bilirubin: 3.4–15.4 µmol/L (0.2–0.9 mg/dL); 95% of healthy adults fall in this range.",
    ]
))
story.append(Spacer(1, 0.5*cm))
story.append(Paragraph("Source: Harrison's Principles of Internal Medicine, 22nd ed., Chapter 52", Ref))

story.append(PageBreak())

# ── SECTION 1: BILIRUBIN METABOLISM ─────────────────────────────────────────
story.append(section_header("1. Bilirubin Metabolism", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("1.1  Formation of Bilirubin", H2))
story.append(Paragraph(
    "Bilirubin is the end-product of heme catabolism. Approximately <b>80–85%</b> derives from "
    "haemoglobin in senescent red blood cells; the remainder comes from myoglobin, cytochromes, "
    "and ineffective erythropoiesis.",
    Body))
story.append(Paragraph(
    "Two sequential enzymatic reactions occur in reticuloendothelial cells (spleen and liver):",
    Body))
story.append(bullet("<b>Step 1 – Heme oxygenase (microsomal):</b> Oxidatively cleaves the α-bridge of the porphyrin ring, opening the heme ring → produces biliverdin + CO + Fe²⁺."))
story.append(bullet("<b>Step 2 – Biliverdin reductase (cytosolic):</b> Reduces the central methylene bridge of biliverdin → unconjugated bilirubin (UCB)."))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("1.2  Transport to the Liver", H2))
story.append(Paragraph(
    "Unconjugated bilirubin (UCB) is <b>virtually water-insoluble</b> because of tight internal hydrogen "
    "bonding between propionic acid carboxyl groups and imino/lactam groups. "
    "It is transported in plasma bound non-covalently to <b>albumin</b> (UCB–albumin complex). "
    "Free UCB is lipid-soluble and can cross the blood–brain barrier (risk of kernicterus).",
    Body))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("1.3  Hepatic Uptake and Conjugation", H2))
story.append(Paragraph(
    "At the hepatocyte sinusoidal surface, UCB dissociates from albumin and enters hepatocytes via "
    "carrier-mediated transport. Inside, UCB binds to cytosolic proteins of the "
    "<b>glutathione-S-transferase superfamily</b>, preventing efflux back into blood.",
    Body))
story.append(Paragraph(
    "In the <b>smooth endoplasmic reticulum</b>, UCB is conjugated to glucuronic acid by "
    "<b>bilirubin UDP-glucuronosyl transferase (UDPGT)</b>:",
    Body))
story.append(bullet("UCB + UDP-glucuronic acid → bilirubin monoglucuronide → bilirubin diglucuronide (predominant conjugated form)."))
story.append(bullet("Conjugation disrupts internal H-bonds → water-soluble conjugated bilirubin (CB)."))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("1.4  Biliary Excretion", H2))
story.append(Paragraph(
    "Conjugated bilirubin diffuses from the ER to the canalicular membrane. "
    "It is actively transported into bile canaliculi by the ATP-dependent transporter "
    "<b>MRP2 (multidrug resistance-associated protein 2)</b>. "
    "A fraction is exported into sinusoidal blood by <b>MRP3</b> and may be recaptured by "
    "hepatocytes via <b>OATP1B1 / OATP1B3</b>.",
    Body))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("1.5  Intestinal Fate and Enterohepatic Circulation", H2))
story.append(Paragraph(
    "Conjugated bilirubin is not absorbed in the proximal small bowel (hydrophilic + large MW). "
    "In the <b>distal ileum and colon</b>, bacterial β-glucuronidases hydrolyse it to UCB, which is "
    "then reduced by gut bacteria to colourless <b>urobilinogens</b>.",
    Body))
story.append(bullet("80–90% of urobilinogens excreted in faeces (unchanged or oxidised to orange-brown urobilins → stool colour)."))
story.append(bullet("10–20% undergo enterohepatic circulation; a small fraction (<3 mg/dL) escapes hepatic re-uptake and is filtered at the glomerulus → excreted as urinary urobilinogen."))
story.append(Spacer(1, 0.3*cm))

# Metabolism summary table
story.append(Paragraph("Summary: Steps in Bilirubin Metabolism", H3))
met_rows = [
    ["Formation",    "Reticuloendothelial cells", "Heme oxygenase + biliverdin reductase", "Unconjugated bilirubin (UCB)"],
    ["Transport",    "Blood",                     "Bound to albumin (non-covalent)",        "UCB–albumin complex"],
    ["Hepatic uptake","Hepatocyte sinusoid",       "Carrier-mediated; GST binding in cytosol","UCB in hepatocyte"],
    ["Conjugation",  "Smooth ER",                 "UDPGT (UDP-glucuronosyl transferase)",   "Bilirubin mono/di-glucuronide (CB)"],
    ["Canalicular excretion","Bile canaliculus",  "MRP2 (ATP-dependent)",                  "CB in bile"],
    ["Intestinal processing","Distal ileum/colon","Bacterial β-glucuronidases + reduction", "Urobilinogens → urobilins / stercobilin"],
    ["Enterohepatic",  "Portal → liver",          "Hepatic re-uptake via OATP1B1/1B3",      "Re-excreted in bile"],
]
story.append(make_table(
    ["Step", "Location", "Enzyme / Mechanism", "Product"],
    met_rows,
    col_widths=[3.2*cm, 3.2*cm, 6.5*cm, 4.3*cm]
))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Source: Harrison's Principles of Internal Medicine, 22nd ed., Chapter 52", Ref))

story.append(PageBreak())

# ── SECTION 2: MEASUREMENT OF BILIRUBIN ─────────────────────────────────────
story.append(section_header("2. Measurement of Serum Bilirubin", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("2.1  Van den Bergh Reaction", H2))
story.append(Paragraph(
    "The traditional method (still used in most labs) exposes serum bilirubin to "
    "<b>diazotized sulfanilic acid</b>, which cleaves bilirubin into two dipyrrylmethene azopigments "
    "(max absorbance 540 nm). Two fractions are measured:",
    Body))
story.append(bullet("<b>Direct fraction (conjugated bilirubin):</b> reacts with diazo reagent without an accelerator."))
story.append(bullet("<b>Total bilirubin:</b> measured after addition of alcohol (accelerator) to release UCB from albumin."))
story.append(bullet("<b>Indirect fraction (unconjugated):</b> Total minus Direct."))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.2  Reference Values", H2))
ref_rows = [
    ["Total serum bilirubin",       "3.4–15.4 µmol/L", "0.2–0.9 mg/dL",  "95% of normal population"],
    ["Unconjugated (indirect)",     "Majority of total","≤ ~1.0 mg/dL",   "Near 100% in normal persons"],
    ["Conjugated (direct)",         "< 15% of total",   "< 0.3 mg/dL",    "Any rise = significant hepatobiliary pathology"],
    ["Overt clinical jaundice",     "> 34 µmol/L",      "> 2 mg/dL",      "Scleral icterus first sign"],
    ["Delta bilirubin (δ-bilirubin)","Covalently bound to albumin","Prolonged cholestasis","Half-life ≈ 18–20 days (albumin t½)"],
]
story.append(make_table(
    ["Parameter", "SI Units", "Conventional Units", "Clinical Note"],
    ref_rows,
    col_widths=[4.5*cm, 3.5*cm, 3.5*cm, 5.7*cm]
))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.3  Delta Bilirubin (Biliprotein)", H2))
story.append(Paragraph(
    "When hepatic excretion of bilirubin glucuronides is impaired, conjugated bilirubin accumulates "
    "in serum. A portion covalently links to albumin to form <b>delta (δ) bilirubin</b>. "
    "Because it is albumin-bound, it is NOT filtered at the renal glomerulus, explaining two "
    "clinical enigmas:",
    Body))
story.append(bullet("Absence of bilirubinuria in some patients with conjugated hyperbilirubinaemia (δ-bilirubin predominates)."))
story.append(bullet("Slow decline in serum bilirubin during recovery (mirrors albumin half-life of 18–20 days)."))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Source: Harrison's Principles of Internal Medicine, 22nd ed.", Ref))

story.append(PageBreak())

# ── SECTION 3: CLASSIFICATION OF JAUNDICE ───────────────────────────────────
story.append(section_header("3. Classification of Jaundice", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "Jaundice is classified by the type of bilirubin elevated and the site of pathology:",
    Body))
story.append(Spacer(1, 0.2*cm))

# Classification table
class_rows = [
    ["Prehepatic\n(Haemolytic)",
     "Unconjugated (indirect)",
     "Increased RBC destruction or ineffective erythropoiesis → ↑ bilirubin production exceeds hepatic conjugation capacity",
     "Haemolytic anaemias (hereditary spherocytosis, G6PD deficiency, sickle-cell, thalassaemia, autoimmune haemolysis), ineffective erythropoiesis, large haematoma resorption"],
    ["Hepatic\n(Hepatocellular)",
     "Mixed (conjugated + unconjugated)",
     "Damaged hepatocytes → impaired uptake, conjugation, and/or excretion of bilirubin",
     "Viral hepatitis (A,B,C,D,E), alcoholic hepatitis, drug-induced liver injury, cirrhosis, autoimmune hepatitis, ischaemic hepatitis, Wilson disease, Gilbert's syndrome, Crigler-Najjar I & II, Dubin-Johnson, Rotor syndrome"],
    ["Posthepatic\n(Obstructive / Cholestatic)",
     "Conjugated (direct)",
     "Obstruction of bile flow (intrahepatic or extrahepatic) → reflux of conjugated bilirubin into blood",
     "Choledocholithiasis, carcinoma head of pancreas, cholangiocarcinoma, PSC, PBC, strictures, cholestasis of pregnancy"],
]
story.append(make_table(
    ["Type", "Predominant Bilirubin", "Mechanism", "Key Causes"],
    class_rows,
    col_widths=[2.5*cm, 3.0*cm, 5.5*cm, 6.2*cm]
))
story.append(Spacer(1, 0.4*cm))

# ── 3.1 Unconjugated Hyperbilirubinaemia ─────────────────────────────────────
story.append(Paragraph("3.1  Isolated Unconjugated Hyperbilirubinaemia", H2))
story.append(Paragraph(
    "This pattern results from either <b>overproduction</b> (haemolysis / ineffective erythropoiesis) "
    "or <b>impaired hepatic uptake / conjugation</b>.",
    Body))

story.append(Paragraph("Haemolytic Disorders", H3))
haem_rows = [
    ["Hereditary spherocytosis",   "Spectrin/ankyrin defect", "AD", "Spherocytes, ↑ MCHC, splenomegaly"],
    ["G6PD deficiency",            "Heinz body haemolysis (oxidative)", "X-linked", "Bite cells, episodic haemolysis"],
    ["Sickle-cell anaemia",        "HbS polymerisation",      "AR", "Sickle cells, vaso-occlusive crises"],
    ["Thalassaemia",               "Ineffective erythropoiesis + haemolysis", "AR", "Hypochromic microcytic anaemia"],
    ["Autoimmune haemolytic anaemia","IgG/IgM anti-RBC antibodies","Acquired","+ Direct Coombs test"],
    ["Microangiopathic (TTP/HUS)", "Shear-stress haemolysis", "Acquired","Schistocytes, ↑LDH"],
]
story.append(make_table(
    ["Disorder", "Mechanism", "Inheritance", "Key Finding"],
    haem_rows,
    col_widths=[4.5*cm, 5.5*cm, 2.5*cm, 4.7*cm]
))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("Genetic Disorders of Bilirubin Conjugation", H3))
gen_rows = [
    ["Gilbert's syndrome",
     "UDPGT activity 10–35% of normal (UGT1A1 promoter TA repeat)",
     "Mild UCB < 6 mg/dL; fluctuates with fasting, stress, illness, alcohol",
     "Very common (3–7% population, M:F = 1.5–7:1); benign; may be hepatoprotective"],
    ["Crigler-Najjar Type I",
     "Complete absence of bilirubin UDPGT activity (UGT1A1 coding mutation)",
     "Severe UCB > 20 mg/dL (>342 µmol/L); kernicterus in neonates",
     "Rare; often fatal in infancy; liver transplant required"],
    ["Crigler-Najjar Type II",
     "UDPGT activity severely reduced (≤10% of normal); phenobarbital-inducible",
     "UCB 6–25 mg/dL (103–428 µmol/L)",
     "More common than type I; survive into adulthood; phenobarbital reduces bilirubin"],
    ["Dubin-Johnson syndrome",
     "Absent MRP2 (canalicular bilirubin transporter) — conjugated bilirubin reflux",
     "Conjugated hyperbilirubinaemia; black liver pigment on biopsy",
     "Benign; urinary coproporphyrin isomer I elevated"],
    ["Rotor syndrome",
     "Absent OATP1B1 + OATP1B3 (hepatic drug re-uptake transporters)",
     "Conjugated hyperbilirubinaemia",
     "Benign; no liver pigment; total urinary coproporphyrin elevated"],
]
story.append(make_table(
    ["Syndrome", "Defect", "Bilirubin Level", "Notes"],
    gen_rows,
    col_widths=[3.5*cm, 5.0*cm, 4.0*cm, 4.7*cm]
))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Source: Harrison's Principles of Internal Medicine, 22nd ed., Chapter 52", Ref))

story.append(PageBreak())

# ── SECTION 4: HEPATOCELLULAR JAUNDICE ───────────────────────────────────────
story.append(section_header("4. Hepatocellular (Hepatic) Jaundice", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "Liver-cell damage impairs all three steps—uptake, conjugation, and excretion—producing "
    "<b>mixed conjugated + unconjugated hyperbilirubinaemia</b>. "
    "Transaminases (ALT, AST) are markedly elevated (hepatocellular pattern).",
    Body))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("4.1  Major Causes", H2))
cause_rows = [
    ["Viral hepatitis A",      "Faeco-oral (HAV)",      "Acute, self-limiting; jaundice in ~70% of adults"],
    ["Viral hepatitis B",      "Parenteral/sexual/vertical","Acute + chronic; risk of cirrhosis/HCC"],
    ["Viral hepatitis C",      "Parenteral (blood)",    "Mostly anicteric acutely; 75–85% chronic"],
    ["Hepatitis E",            "Faeco-oral (HEV)",      "Dangerous in pregnancy (high mortality)"],
    ["Alcoholic hepatitis",    "Ethanol toxicity",      "AST:ALT > 2:1; neutrophilic infiltrate; Mallory bodies"],
    ["Drug-induced (DILI)",    "Hepatotoxic drugs/herbs","Paracetamol (dose-dependent); idiosyncratic agents"],
    ["Autoimmune hepatitis",   "Anti-liver autoantibodies","ANA, anti-SMA, anti-LKM1; steroid-responsive"],
    ["Ischaemic hepatitis",    "Hypoperfusion",         "Transaminases >1000 IU/L rapidly; 'shock liver'"],
    ["Wilson disease",         "Copper accumulation (ATP7B mutation)","Haemolysis + liver disease in young adults"],
    ["Cirrhosis",              "End-stage fibrosis (any cause)","Reduced synthetic function + portal hypertension"],
]
story.append(make_table(
    ["Cause", "Mechanism / Exposure", "Key Feature"],
    cause_rows,
    col_widths=[4.5*cm, 5.0*cm, 7.7*cm]
))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("4.2  Histological Features of Hepatocellular Damage", H2))
for txt in [
    "Hepatocyte necrosis and apoptosis (acidophilic bodies / Councilman bodies in viral hepatitis)",
    "Lobular disarray with inflammatory infiltrate (lymphocytes in viral; neutrophils in alcoholic)",
    "Mallory–Denk bodies (alcoholic hepatitis and NASH): intracytoplasmic eosinophilic inclusions of cytokeratin 8/18",
    "Ballooning degeneration of hepatocytes",
    "Zone 3 (centrilobular) necrosis in ischaemic hepatitis and paracetamol toxicity",
    "Ground-glass hepatocytes in chronic HBV (HBsAg accumulation)",
    "Bridging necrosis and fibrosis leading to cirrhosis in chronic disease",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("4.3  Liver Function Tests in Hepatocellular Disease", H2))
lft_rows = [
    ["ALT (SGPT)",         "↑↑↑ (often > 10× ULN)",     "Most specific marker of hepatocyte damage"],
    ["AST (SGOT)",         "↑↑↑",                        "Less specific (also in muscle, heart); AST:ALT > 2:1 in alcoholic hepatitis"],
    ["Bilirubin (total)",  "↑ (mixed pattern)",           "Both conjugated and unconjugated elevated"],
    ["Alkaline phosphatase","Normal or mildly ↑",         "Markedly elevated in cholestatic disease"],
    ["GGT",                "↑ in alcoholic / cholestatic","Useful for confirming hepatic source of ALP"],
    ["PT / INR",           "↑ in severe disease",         "Reflects synthetic function (factors I, II, V, VII, X)"],
    ["Albumin",            "↓ in chronic disease",        "Marker of chronic synthetic failure"],
    ["Urinary urobilinogen","↑↑",                         "More bilirubin reaches gut → more urobilinogen reabsorbed"],
    ["Urinary bilirubin",  "Present",                     "Conjugated bilirubin filtered by glomerulus"],
]
story.append(make_table(
    ["Test", "Result", "Comment"],
    lft_rows,
    col_widths=[4.0*cm, 4.5*cm, 8.7*cm]
))

story.append(PageBreak())

# ── SECTION 5: OBSTRUCTIVE JAUNDICE ─────────────────────────────────────────
story.append(section_header("5. Obstructive (Cholestatic / Posthepatic) Jaundice", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "Obstruction of bile flow causes <b>conjugated bilirubin</b> to reflux from bile ducts into "
    "blood. Distinguishing intrahepatic from extrahepatic cholestasis is key to management.",
    Body))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("5.1  Causes", H2))
obs_rows = [
    ["Extrahepatic","Choledocholithiasis",           "Most common cause; gallstones in CBD; may be associated with cholangitis"],
    ["Extrahepatic","Pancreatic carcinoma (head)",   "Painless progressive jaundice; Courvoisier's sign (palpable non-tender GB)"],
    ["Extrahepatic","Cholangiocarcinoma",             "Klatskin tumour at biliary hilum; insidious onset; weight loss"],
    ["Extrahepatic","Periampullary carcinoma",        "Episodic jaundice (tumour necrosis)"],
    ["Extrahepatic","Stricture / trauma",             "Post-cholecystectomy bile duct injury"],
    ["Extrahepatic","Pancreatitis (chronic)",         "Compression of common bile duct"],
    ["Intrahepatic","Primary biliary cholangitis (PBC)","Autoimmune destruction of small bile ducts; AMA positive; middle-aged women"],
    ["Intrahepatic","Primary sclerosing cholangitis (PSC)","Fibro-inflammatory strictures; ERCP shows 'beaded' bile ducts; associated with UC"],
    ["Intrahepatic","Intrahepatic cholestasis of pregnancy","Late pregnancy; UDCA treatment"],
    ["Intrahepatic","Drug-induced cholestasis",       "Anabolic steroids, OCP, chlorpromazine, rifampicin"],
    ["Intrahepatic","Infiltrative diseases",          "Sarcoidosis, amyloidosis, lymphoma, metastases"],
]
story.append(make_table(
    ["Site", "Cause", "Notes"],
    obs_rows,
    col_widths=[2.8*cm, 5.0*cm, 9.4*cm]
))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("5.2  Pathophysiology of Obstructive Jaundice", H2))
for txt in [
    "Bile duct obstruction → backpressure → conjugated bilirubin regurgitates into sinusoidal blood",
    "Conjugated bilirubin appears in urine → dark 'tea/cola-coloured' urine (bilirubinuria)",
    "Absent bile in gut → acholic (pale clay-coloured) stools; reduced urobilinogen in urine",
    "Bile salt accumulation in skin → intense pruritus",
    "Fat malabsorption → steatorrhoea + deficiency of fat-soluble vitamins (A, D, E, K)",
    "Vitamin K deficiency → coagulopathy (prolonged PT); responds to parenteral vitamin K",
    "Secondary biliary cirrhosis in prolonged obstruction",
    "Ascending cholangitis risk (Charcot's triad: fever + RUQ pain + jaundice; Reynolds' pentad adds shock + altered consciousness)",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("5.3  LFTs in Obstructive Jaundice", H2))
obs_lft_rows = [
    ["Bilirubin",           "↑↑ (predominantly conjugated)","Bilirubinuria present"],
    ["ALP",                 "↑↑↑ (often > 3× ULN)",        "Most sensitive marker of cholestasis; from bile duct epithelium"],
    ["GGT",                 "↑↑",                           "Confirms hepatic source of ↑ALP"],
    ["ALT / AST",           "Normal or mildly ↑",           "Markedly elevated if secondary hepatocyte damage"],
    ["Prothrombin time",    "Prolonged (if chronic)",        "Due to vitamin K malabsorption; reverses with IV vitamin K"],
    ["Urinary urobilinogen","↓ or absent",                  "Bile not reaching gut → no urobilinogen formed"],
    ["Stool colour",        "Pale / acholic",                "Absence of stercobilin"],
]
story.append(make_table(
    ["Test", "Result", "Explanation"],
    obs_lft_rows,
    col_widths=[4.0*cm, 4.5*cm, 8.7*cm]
))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Sources: Harrison's 22nd ed.; Sleisenger & Fordtran's GI and Liver Disease, Chapter 21", Ref))

story.append(PageBreak())

# ── SECTION 6: CLINICAL EVALUATION ──────────────────────────────────────────
story.append(section_header("6. Clinical Evaluation of Jaundice", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("6.1  History", H2))
for txt in [
    "<b>Onset and duration:</b> acute vs. chronic; intermittent (choledocholithiasis) vs. progressive (malignancy)",
    "<b>Associated symptoms:</b> pruritus (cholestasis), RUQ pain (biliary colic, cholangitis), fever/rigors (cholangitis), weight loss (malignancy)",
    "<b>Urine/stool changes:</b> dark urine (bilirubinuria), pale stools (acholia) – point to obstructive cause",
    "<b>Drug/toxin history:</b> prescribed meds, OTC drugs, herbal supplements, alcohol, anabolic steroids",
    "<b>Viral hepatitis risk factors:</b> IV drug use, tattoos, sexual history, blood transfusions, travel",
    "<b>Family history:</b> Gilbert's, haemolytic anaemia, Wilson disease",
    "<b>Occupational/toxic exposure:</b> industrial solvents, heavy metals",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("6.2  Physical Examination", H2))
pe_rows = [
    ["Scleral icterus",            "First and most sensitive sign of jaundice (bilirubin > 2 mg/dL)"],
    ["Skin colour",                "Lemon-yellow (haemolytic); deep yellow-green (obstructive)"],
    ["Scratch marks",              "Pruritus from bile salt deposition (cholestasis)"],
    ["Hepatomegaly",               "Hepatitis, fatty liver, infiltrative disease, malignancy"],
    ["Splenomegaly",               "Haemolytic jaundice, portal hypertension, chronic liver disease"],
    ["Palpable gallbladder (Courvoisier)", "Obstruction by pancreatic/periampullary malignancy; GB not palpable in gallstone disease"],
    ["Signs of chronic liver disease","Spider naevi, palmar erythema, caput medusae, gynaecomastia, leuconychia, dupuytren, asterixis"],
    ["Ascites",                    "Portal hypertension / hypoalbuminaemia in cirrhosis or malignancy"],
    ["Kayser-Fleischer rings",     "Wilson disease (slit-lamp examination of cornea)"],
    ["Lymphadenopathy",            "Lymphoma, metastatic malignancy"],
    ["RUQ tenderness",             "Acute cholecystitis, hepatitis, biliary colic"],
    ["Murphy's sign",              "Acute cholecystitis (cessation of inspiration on RUQ palpation)"],
]
story.append(make_table(
    ["Finding", "Significance"],
    pe_rows,
    col_widths=[5.5*cm, 11.7*cm]
))

story.append(PageBreak())

story.append(Paragraph("6.3  Laboratory Investigation Algorithm", H2))
story.append(Paragraph(
    "Initial evaluation: determine whether hyperbilirubinaemia is <b>predominantly unconjugated or conjugated</b>. "
    "If conjugated, check whether other liver tests are abnormal.",
    Body))
story.append(Spacer(1, 0.2*cm))

algo_rows = [
    ["↑ Unconjugated bilirubin only\n(indirect fraction > 85% of total)",
     "No other LFT abnormalities",
     "Haemolysis (FBC, reticulocytes, Coombs test, LDH, haptoglobin)\nor Gilbert's / Crigler-Najjar"],
    ["↑ Conjugated bilirubin\n+↑ ALT/AST >> ALP",
     "Hepatocellular pattern",
     "Viral serology (HAV-IgM, HBsAg, anti-HCV), ANA, anti-SMA, ceruloplasmin, copper, alcohol history"],
    ["↑ Conjugated bilirubin\n+↑ ALP >> ALT/AST",
     "Cholestatic pattern",
     "Ultrasound abdomen (dilated ducts → extrahepatic; non-dilated → intrahepatic)\nMRCP, ERCP, liver biopsy, AMA, ANCA"],
]
story.append(make_table(
    ["Bilirubin Pattern", "LFT Pattern", "Next Investigations"],
    algo_rows,
    col_widths=[4.5*cm, 3.5*cm, 9.2*cm]
))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("6.4  Imaging and Invasive Investigations", H2))
img_rows = [
    ["Ultrasound abdomen",   "1st-line for jaundice","Dilated bile ducts → extrahepatic obstruction; gallstones, liver parenchyma"],
    ["MRCP",                 "Non-invasive biliary imaging","Detailed biliary anatomy; diagnosis of choledocholithiasis, PSC, strictures"],
    ["ERCP",                 "Diagnostic + therapeutic","Sphincterotomy, stone extraction, stent placement; risk of pancreatitis"],
    ["CECT abdomen",         "Pancreatic/hepatic pathology","Pancreatic carcinoma, metastases, hepatic masses"],
    ["PTC (Percutaneous transhepatic cholangiography)","When ERCP fails","Drainage of intrahepatic ducts; proximal biliary obstruction"],
    ["Liver biopsy",         "Parenchymal liver disease","Hepatitis grading/staging, PBC, autoimmune hepatitis, Wilson disease"],
    ["Endoscopic ultrasound (EUS)","Periampullary & pancreatic lesions","Staging, FNA of pancreatic masses"],
]
story.append(make_table(
    ["Investigation", "Indication", "Key Use"],
    img_rows,
    col_widths=[4.5*cm, 4.5*cm, 8.2*cm]
))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Source: Sleisenger & Fordtran's GI and Liver Disease, Chapter 21; Harrison's 22nd ed., Chapter 52", Ref))

story.append(PageBreak())

# ── SECTION 7: NEONATAL JAUNDICE ─────────────────────────────────────────────
story.append(section_header("7. Neonatal Jaundice", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "Jaundice in the newborn is extremely common and may be physiological or pathological. "
    "Unconjugated bilirubin is neurotoxic in neonates.",
    Body))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("7.1  Physiological Jaundice", H2))
for txt in [
    "Appears on <b>day 2–3</b> of life (never day 1)",
    "Peaks day 3–5; resolves by day 10–14 (may persist to 3 weeks in preterm)",
    "Mechanism: fetal Hb breakdown → ↑ bilirubin load; immature hepatic UDPGT activity; increased enterohepatic circulation",
    "Bilirubin < 12 mg/dL in term infant; < 15 mg/dL in preterm",
    "No treatment usually required",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("7.2  Pathological Jaundice – Red Flags", H2))
for txt in [
    "Jaundice appearing within <b>24 hours</b> of birth",
    "Bilirubin rising > 5 mg/dL/day",
    "Serum bilirubin > 15 mg/dL in term infant",
    "Jaundice persisting > 14 days (term) or > 21 days (preterm)",
    "Conjugated (direct) bilirubin > 2 mg/dL at any age",
    "Signs of haemolysis (pallor, hydrops fetalis, hepatosplenomegaly)",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("7.3  Causes of Neonatal Pathological Jaundice", H2))
neo_rows = [
    ["Haemolytic – immune", "Rh incompatibility (anti-D), ABO incompatibility, minor blood group antigens", "Coombs test positive", "Day 1"],
    ["Haemolytic – non-immune","G6PD deficiency, hereditary spherocytosis, alpha-thalassaemia","Peripheral blood smear","Variable"],
    ["Infection",           "Bacterial sepsis, congenital TORCH infections","CRP, blood cultures, TORCH screen","Any day"],
    ["Metabolic",           "Galactosaemia, hypothyroidism, tyrosinaemia","Metabolic screen","Variable"],
    ["Biliary atresia",     "Fibro-obliterative destruction of bile ducts","↑ Conjugated bilirubin, HIDA scan","Weeks 2–6"],
    ["Crigler-Najjar I",    "Absent UDPGT",    "Bilirubin > 20 mg/dL","Day 1–3"],
    ["Breast-milk jaundice","β-glucuronidase in breast milk → ↑ enterohepatic circulation","Clinical; temporary formula feeds","Week 2+"],
]
story.append(make_table(
    ["Cause", "Details", "Investigation", "Onset"],
    neo_rows,
    col_widths=[3.2*cm, 5.5*cm, 4.5*cm, 2.0*cm]
))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("7.4  Kernicterus (Bilirubin Encephalopathy)", H2))
story.append(Paragraph(
    "Unconjugated bilirubin at very high levels crosses the blood–brain barrier and deposits in "
    "the basal ganglia, hippocampus, and brainstem nuclei, causing irreversible neuronal necrosis. "
    "Characteristic yellow staining of the brain is called <b>kernicterus</b>.",
    Body))
for txt in [
    "<b>Acute phase:</b> hypotonia, poor feeding, high-pitched cry, seizures, opisthotonus",
    "<b>Chronic phase:</b> choreoathetosis, sensorineural deafness, upward gaze palsy, intellectual disability",
    "<b>Treatment:</b> phototherapy (converts bilirubin to water-soluble photoisomers via blue-green light 460–490 nm) and exchange transfusion for severe cases",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Source: Rosen's Emergency Medicine; Harrison's 22nd ed.", Ref))

story.append(PageBreak())

# ── SECTION 8: DIFFERENTIAL DIAGNOSIS ────────────────────────────────────────
story.append(section_header("8. Differential Diagnosis at a Glance", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

dd_rows = [
    ["Feature",              "Haemolytic (Prehepatic)", "Hepatocellular (Hepatic)", "Obstructive (Posthepatic)"],
    ["Bilirubin type",       "Unconjugated ↑↑",         "Both ↑",                   "Conjugated ↑↑"],
    ["Urine bilirubin",      "Absent",                  "Present",                  "Present (dark)"],
    ["Urinary urobilinogen", "↑↑↑",                     "↑ (early) or ↓ (severe)",  "↓ or absent"],
    ["Stool colour",         "Normal / dark",           "Variable",                 "Pale / acholic"],
    ["ALT / AST",            "Normal",                  "↑↑↑",                      "Normal / mild ↑"],
    ["ALP",                  "Normal",                  "Normal / mild ↑",          "↑↑↑"],
    ["PT / INR",             "Normal",                  "↑ (if severe)",            "↑ (responds to vit. K)"],
    ["Haemoglobin",          "↓ (anaemia)",             "Usually normal",           "Normal"],
    ["Splenomegaly",         "Common",                  "Present (portal HT)",      "Absent (usually)"],
    ["Gallbladder",          "Not enlarged",            "Not enlarged",             "Enlarged if below cystic duct (Courvoisier)"],
    ["Key investigation",    "CBC, reticulocytes, Coombs","Viral serology, LFTs, biopsy","USS, MRCP, ERCP"],
]
# Header row separate
header = dd_rows[0]
data_r = dd_rows[1:]
story.append(make_table(header, data_r, col_widths=[4.3*cm, 4.0*cm, 4.0*cm, 4.9*cm]))
story.append(Spacer(1, 0.4*cm))

# ── SECTION 9: MANAGEMENT ────────────────────────────────────────────────────
story.append(section_header("9. Management Principles", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("9.1  Obstructive Jaundice", H2))
for txt in [
    "Therapy directed at <b>relieving obstruction</b>",
    "<b>ERCP</b>: sphincterotomy, balloon dilation of strictures, stent placement (for distal lesions, choledocholithiasis)",
    "<b>Interventional radiology (PTC)</b>: biliary drain for proximal obstruction (Klatskin tumour)",
    "<b>Surgery</b>: for resectable malignancies; biliary bypass for palliation",
    "Correct coagulopathy with parenteral <b>vitamin K</b> before any procedure",
    "<b>Broad-spectrum antibiotics</b> for ascending cholangitis (e.g., piperacillin-tazobactam)",
    "<b>UDCA (ursodeoxycholic acid)</b>: for PBC and cholestasis of pregnancy – stimulates bile flow, improves biochemistry",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("9.2  Hepatocellular Jaundice", H2))
for txt in [
    "Treat underlying cause: antiviral therapy (DAAs for HCV; tenofovir/entecavir for HBV); cessation of offending drug/alcohol",
    "Immunosuppressants (prednisolone ± azathioprine) for autoimmune hepatitis",
    "N-acetylcysteine (NAC) for paracetamol-induced acute liver failure",
    "Liver transplantation for fulminant hepatic failure or end-stage chronic liver disease",
    "Supportive care: nutrition, coagulopathy management, infection prevention",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("9.3  Haemolytic Jaundice", H2))
for txt in [
    "Treat underlying haemolytic condition (steroids for AIHA, transfusions, splenectomy in hereditary spherocytosis)",
    "Folate supplementation (↑ demand from erythroid hyperplasia)",
    "Avoid triggers for G6PD deficiency (oxidant drugs, fava beans)",
    "Phototherapy or exchange transfusion for neonatal jaundice with kernicterus risk",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("9.4  Pruritus in Cholestasis", H2))
for txt in [
    "Cholestyramine (bile acid resin) – first-line",
    "Rifampicin – second-line (monitor hepatotoxicity)",
    "Naltrexone (opioid antagonist) – third-line; reverses opioid analgesia",
    "Sertraline (SSRI)",
    "UVB phototherapy",
    "Cool temperatures, emollients, topical steroids for symptomatic relief",
]:
    story.append(bullet(txt))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Sources: Sleisenger & Fordtran's GI and Liver Disease, Chapter 21; Harrison's 22nd ed., Chapter 52", Ref))

story.append(PageBreak())

# ── SECTION 10: HIGH-YIELD SUMMARY BOX ───────────────────────────────────────
story.append(section_header("10. High-Yield Summary for Examinations", DARK_BLUE))
story.append(Spacer(1, 0.3*cm))

hy_data = [
    ["Topic", "Key Point"],
    ["Bilirubin normal range",   "0.2–0.9 mg/dL total; clinical jaundice > 2 mg/dL"],
    ["First step in evaluation", "Is bilirubin predominantly conjugated or unconjugated?"],
    ["UCB only, isolated",       "Haemolysis OR Gilbert's / Crigler-Najjar (check CBC, retics, Coombs)"],
    ["CB + ↑ALP >> ALT",         "Cholestatic pattern → USS abdomen (dilated ducts?)"],
    ["CB + ↑ALT >> ALP",         "Hepatocellular pattern → viral serology, autoimmune workup"],
    ["Courvoisier's law",        "Painless jaundice + non-tender palpable GB → malignant obstruction (not stones)"],
    ["Charcot's triad",          "Fever + RUQ pain + jaundice → acute cholangitis"],
    ["Reynolds' pentad",         "Charcot's triad + shock + altered consciousness → suppurative cholangitis"],
    ["Gilbert's syndrome",       "Most common hereditary cause of UCB; benign; 3–7% population; ↑ with fasting"],
    ["Crigler-Najjar I",         "No UDPGT; kernicterus; fatal without liver transplant"],
    ["Dubin-Johnson",            "MRP2 defect; conjugated CB; black liver pigment; benign"],
    ["Rotor syndrome",           "OATP1B1/1B3 defect; conjugated CB; no liver pigment; benign"],
    ["Delta bilirubin",          "Covalently albumin-bound CB; t½ = 18–20 days; explains persistent jaundice during recovery"],
    ["Kernicterus bilirubin",    "UCB > 20 mg/dL in neonate; phototherapy (460–490 nm) is primary treatment"],
    ["PBC marker",               "Anti-mitochondrial antibody (AMA); small bile duct destruction; UDCA treatment"],
    ["PSC association",          "Ulcerative colitis; 'beaded' bile ducts on ERCP/MRCP; risk of cholangiocarcinoma"],
    ["AST:ALT > 2:1",            "Alcoholic hepatitis (also: Wilson disease can show this pattern)"],
    ["Vitamin K response",       "Obstructive jaundice → PT corrects with IV vitamin K (fat malabsorption); hepatocellular → PT does NOT correct"],
]
story.append(make_table(
    hy_data[0],
    hy_data[1:],
    col_widths=[5.5*cm, 11.7*cm]
))
story.append(Spacer(1, 0.3*cm))

# ── REFERENCES ───────────────────────────────────────────────────────────────
story.append(hr(DARK_BLUE, 1.5))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("<b>References</b>", H2))
refs = [
    "Longo DL, et al. <i>Harrison's Principles of Internal Medicine</i>, 22nd Edition. McGraw-Hill, 2025. Chapter 52: Jaundice.",
    "Feldman M, Friedman LS, Brandt LJ. <i>Sleisenger and Fordtran's Gastrointestinal and Liver Disease</i>, 11th Edition. Elsevier, 2021. Chapter 21: Jaundice.",
    "Marx J, et al. <i>Rosen's Emergency Medicine</i>, 10th Edition. Elsevier. Chapter 24 & 166: Jaundice (Adult & Neonatal).",
    "Kumar V, Abbas AK, Aster JC. <i>Robbins & Cotran Pathologic Basis of Disease</i>. Elsevier. Chapter 18: Liver and Biliary Tract.",
    "Pye's Surgical Handicraft, 22nd Edition. Chapter: Jaundice.",
]
for r in refs:
    story.append(Paragraph(f"\u2022  {r}", Ref))

story.append(Spacer(1, 0.5*cm))
story.append(hr(BORDER_GREY))
story.append(Paragraph(
    "This document was compiled from authoritative medical textbooks via the Orris Medical Library. "
    "It is intended for educational purposes only.",
    Caption))

# ── BUILD ─────────────────────────────────────────────────────────────────────
def on_page(canvas, doc):
    canvas.saveState()
    # header bar
    canvas.setFillColor(DARK_BLUE)
    canvas.rect(2*cm, A4[1]-1.5*cm, A4[0]-4*cm, 0.6*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 8)
    canvas.drawString(2.2*cm, A4[1]-1.2*cm, "JAUNDICE – PATHOLOGY REVIEW")
    canvas.setFont("Helvetica", 8)
    canvas.drawRightString(A4[0]-2.2*cm, A4[1]-1.2*cm, "Orris Medical Library | June 2026")
    # footer
    canvas.setFillColor(DARK_BLUE)
    canvas.rect(2*cm, 1.2*cm, A4[0]-4*cm, 0.4*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7.5)
    canvas.drawCentredString(A4[0]/2, 1.35*cm, f"Page {doc.page}")
    canvas.restoreState()

doc.build(story, onFirstPage=on_page, onLaterPages=on_page)
print("PDF generated successfully:", OUTPUT)