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, Image, KeepTogether, PageBreak
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus.flowables import HRFlowable
import os

ASSETS = "/tmp/workspace/folic-acid-pdf/assets"
OUT    = "/tmp/workspace/folic-acid-pdf/Folic_Acid_Summary_Rafi.pdf"

# ── Colours ──────────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1a3a5c")
MID_BLUE    = colors.HexColor("#2e6da4")
LIGHT_BLUE  = colors.HexColor("#d6e8f7")
ACCENT      = colors.HexColor("#e07b00")   # orange (like Rafi cover)
BOX_BG      = colors.HexColor("#fff8f0")
WARN_BG     = colors.HexColor("#fff3cd")
WARN_BORDER = colors.HexColor("#ffc107")
GREEN_BG    = colors.HexColor("#e8f5e9")
RED_BG      = colors.HexColor("#fce4ec")
GREY_LINE   = colors.HexColor("#cccccc")
WHITE       = colors.white
BLACK       = colors.black

doc = SimpleDocTemplate(
    OUT,
    pagesize=A4,
    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=2*cm,    bottomMargin=2*cm,
    title="Folic Acid – Biochemistry Summary",
    author="Rafi MD Style | Textbook of Biochemistry 5th Ed."
)

W, H = A4
CONTENT_W = W - 3.6*cm

styles = getSampleStyleSheet()

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

cover_title = S("CoverTitle", fontSize=28, textColor=WHITE,
                fontName="Helvetica-Bold", alignment=TA_CENTER, leading=34)
cover_sub   = S("CoverSub",   fontSize=14, textColor=colors.HexColor("#ffd580"),
                fontName="Helvetica-BoldOblique", alignment=TA_CENTER, leading=20)
cover_meta  = S("CoverMeta",  fontSize=10, textColor=colors.HexColor("#ccddee"),
                fontName="Helvetica", alignment=TA_CENTER, leading=14)

sec_hd  = S("SecHead",  fontSize=13, textColor=WHITE,
             fontName="Helvetica-Bold", alignment=TA_LEFT, leading=17,
             backColor=DARK_BLUE, leftIndent=-6, rightIndent=-6,
             spaceBefore=10, spaceAfter=4,
             borderPadding=(4,6,4,6))

sub_hd  = S("SubHead",  fontSize=11, textColor=DARK_BLUE,
             fontName="Helvetica-Bold", alignment=TA_LEFT, leading=15,
             spaceBefore=8, spaceAfter=3)

body    = S("Body",     fontSize=9.5, textColor=BLACK,
             fontName="Helvetica", alignment=TA_JUSTIFY, leading=14,
             spaceAfter=3)

bullet  = S("Bullet",   fontSize=9.5, textColor=BLACK,
             fontName="Helvetica", leftIndent=14, firstLineIndent=-10,
             leading=14, spaceAfter=2)

remember= S("Remember", fontSize=9, textColor=colors.HexColor("#7b3f00"),
             fontName="Helvetica-BoldOblique", leading=13,
             backColor=BOX_BG, borderPadding=(4,8,4,8),
             leftIndent=8, rightIndent=8, spaceAfter=4)

warn    = S("Warn",     fontSize=9, textColor=colors.HexColor("#856404"),
             fontName="Helvetica-Bold", leading=13,
             backColor=WARN_BG, borderPadding=(4,8,4,8),
             leftIndent=8, rightIndent=8, spaceAfter=4)

caption = S("Caption",  fontSize=8, textColor=colors.HexColor("#444444"),
             fontName="Helvetica-Oblique", alignment=TA_CENTER, leading=11,
             spaceAfter=6)

footer_s= S("Footer",   fontSize=7.5, textColor=colors.HexColor("#888888"),
             fontName="Helvetica", alignment=TA_CENTER)

# ── Helper builders ──────────────────────────────────────────────────────────
def section(title):
    """Dark blue full-width section header."""
    tbl = Table([[Paragraph(title, sec_hd)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
        ("LEFTPADDING",  (0,0), (-1,-1), 8),
        ("RIGHTPADDING", (0,0), (-1,-1), 8),
        ("TOPPADDING",   (0,0), (-1,-1), 5),
        ("BOTTOMPADDING",(0,0), (-1,-1), 5),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return tbl

def key_box(text, bg=LIGHT_BLUE, border=MID_BLUE):
    tbl = Table([[Paragraph(text, body)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,-1), bg),
        ("BOX",          (0,0),(-1,-1), 1, border),
        ("LEFTPADDING",  (0,0),(-1,-1), 10),
        ("RIGHTPADDING", (0,0),(-1,-1), 10),
        ("TOPPADDING",   (0,0),(-1,-1), 6),
        ("BOTTOMPADDING",(0,0),(-1,-1), 6),
        ("ROUNDEDCORNERS",[4]),
    ]))
    return tbl

def img_block(fname, w_cm, cap):
    path = os.path.join(ASSETS, fname)
    try:
        im = Image(path, width=w_cm*cm, kind='proportional')
        im.hAlign = "CENTER"
        return [im, Paragraph(cap, caption)]
    except Exception as e:
        return [Paragraph(f"[Image: {cap}]", caption)]

def bullet_list(items):
    return [Paragraph(f"• {i}", bullet) for i in items]

def make_table(header, rows, col_widths, header_bg=DARK_BLUE, alt_bg=LIGHT_BLUE):
    data = [header] + rows
    n = len(data)
    tbl = Table(data, colWidths=col_widths)
    ts = [
        ("BACKGROUND",   (0,0),(-1,0),  header_bg),
        ("TEXTCOLOR",    (0,0),(-1,0),  WHITE),
        ("FONTNAME",     (0,0),(-1,0),  "Helvetica-Bold"),
        ("FONTSIZE",     (0,0),(-1,-1), 8.5),
        ("FONTNAME",     (0,1),(-1,-1), "Helvetica"),
        ("GRID",         (0,0),(-1,-1), 0.4, GREY_LINE),
        ("ROWBACKGROUNDS",(0,1),(-1,-1),[WHITE, alt_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),
        ("VALIGN",       (0,0),(-1,-1), "MIDDLE"),
        ("WORDWRAP",     (0,0),(-1,-1), True),
    ]
    tbl.setStyle(TableStyle(ts))
    return tbl

# ── Cover page ───────────────────────────────────────────────────────────────
def cover_page():
    elems = []
    # top colour block
    cover_tbl = Table(
        [[
            Paragraph("FOLIC ACID", cover_title),
        ],
        [
            Paragraph("Vitamin B9 / Folate", cover_sub),
        ],
        [
            Paragraph("Biochemistry Summary  •  NMC/CBME Curriculum", cover_meta),
        ],
        [
            Paragraph("Based on: Textbook of Biochemistry 5th Ed. – Rafi MD", cover_meta),
        ]],
        colWidths=[CONTENT_W]
    )
    cover_tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), DARK_BLUE),
        ("LEFTPADDING",   (0,0),(-1,-1), 20),
        ("RIGHTPADDING",  (0,0),(-1,-1), 20),
        ("TOPPADDING",    (0,0),(0,0),   30),
        ("BOTTOMPADDING", (0,3),(-1,-1), 30),
        ("TOPPADDING",    (0,1),(-1,-1), 4),
        ("BOTTOMPADDING", (0,0),(-1,2),  4),
    ]))
    elems.append(cover_tbl)
    elems.append(Spacer(1, 0.5*cm))

    # quick-reference highlight strip
    qr = [
        ["TOPIC", "KEY FACT"],
        ["Active form", "Tetrahydrofolate (THF)"],
        ["Main function", "One-carbon (1C) unit transfer"],
        ["Best dietary source", "Green leafy vegetables"],
        ["Deficiency hallmark", "Megaloblastic (macrocytic) anemia"],
        ["Unique: NO neurological deficit", "Unlike Vitamin B12 deficiency"],
        ["NTD prevention dose", "400 µg/day before conception"],
    ]
    qr_tbl = Table(qr, colWidths=[CONTENT_W*0.48, CONTENT_W*0.52])
    qr_tbl.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,0),  ACCENT),
        ("TEXTCOLOR",    (0,0),(-1,0),  WHITE),
        ("FONTNAME",     (0,0),(-1,0),  "Helvetica-Bold"),
        ("FONTSIZE",     (0,0),(-1,-1), 8.5),
        ("FONTNAME",     (0,1),(-1,-1), "Helvetica"),
        ("GRID",         (0,0),(-1,-1), 0.5, GREY_LINE),
        ("ROWBACKGROUNDS",(0,1),(-1,-1),[WHITE, BOX_BG]),
        ("LEFTPADDING",  (0,0),(-1,-1), 8),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
    ]))
    elems.append(qr_tbl)
    elems.append(Spacer(1, 0.4*cm))
    # anemia classification diagram
    elems += img_block("anemia_classification.png", 8,
                       "Fig 1. Classification of Nutritional Anemias by RBC size (MCV)\n"
                       "Source: Lippincott Illustrated Reviews – Biochemistry 8th Ed.")
    elems.append(PageBreak())
    return elems

# ── Build story ──────────────────────────────────────────────────────────────
story = []
story += cover_page()

# ── 1. Chemistry & Forms ─────────────────────────────────────────────────────
story.append(section("1.  Chemistry & Forms of Folic Acid"))
story.append(Spacer(1,4))
story.append(Paragraph(
    "Folic acid (pteroylmonoglutamic acid) is a water-soluble B-complex vitamin. "
    "It consists of three components:", body))
story += bullet_list([
    "<b>Pteridine ring</b> – bicyclic nitrogen-containing ring",
    "<b>Para-aminobenzoic acid (PABA)</b> – middle bridge",
    "<b>Glutamic acid</b> – 1 residue in synthetic folic acid; up to 7 in dietary folates (polyglutamates)",
])
story.append(Spacer(1, 6))

forms_header = [
    Paragraph("<b>Form</b>", body),
    Paragraph("<b>Description</b>", body),
    Paragraph("<b>Note</b>", body),
]
forms_rows = [
    [Paragraph("Folic acid", body),
     Paragraph("Synthetic oxidised form", body),
     Paragraph("Supplements & fortified foods", body)],
    [Paragraph("Dietary folate", body),
     Paragraph("Natural polyglutamate form", body),
     Paragraph("Food sources; heat-labile", body)],
    [Paragraph("Dihydrofolate (DHF)", body),
     Paragraph("Partially reduced intermediate", body),
     Paragraph("Product of thymidylate synthase rxn", body)],
    [Paragraph("<b>Tetrahydrofolate (THF)</b>", body),
     Paragraph("<b>Active coenzyme form</b>", body),
     Paragraph("Produced by DHFR; carries 1C units", body)],
    [Paragraph("N⁵-methyl THF", body),
     Paragraph("Main circulating blood form", body),
     Paragraph("Donates –CH₃ to homocysteine (needs B12)", body)],
    [Paragraph("N⁵,N¹⁰-methylene THF", body),
     Paragraph("One-carbon donor for DNA synthesis", body),
     Paragraph("Donates –CH₂ for TMP synthesis", body)],
    [Paragraph("Folinic acid (5-formyl THF / Leucovorin)", body),
     Paragraph("Stable pharmaceutical form", body),
     Paragraph("Rescues cells after methotrexate toxicity", body)],
]
story.append(make_table(forms_header, forms_rows,
    [CONTENT_W*0.25, CONTENT_W*0.35, CONTENT_W*0.40]))
story.append(Spacer(1, 6))
story.append(key_box(
    "⬛ <b>Conversion:</b>  Folic acid  →<sup>(DHFR)</sup>→  DHF  →<sup>(DHFR)</sup>→  <b>THF (active)</b>  "
    "| DHFR = dihydrofolate reductase (target of methotrexate & trimethoprim)",
    bg=LIGHT_BLUE, border=MID_BLUE))
story.append(Spacer(1, 8))

# ── 2. Sources ───────────────────────────────────────────────────────────────
story.append(section("2.  Dietary Sources"))
story.append(Spacer(1,4))
src_header = [Paragraph("<b>Source Type</b>", body), Paragraph("<b>Examples</b>", body),
              Paragraph("<b>Folate Content</b>", body)]
src_rows = [
    [Paragraph("Green leafy vegetables", body),
     Paragraph("Spinach, cabbage, broccoli, fenugreek, lettuce", body),
     Paragraph("⭐ Best natural source", body)],
    [Paragraph("Organ meats", body),
     Paragraph("Liver, kidney", body),
     Paragraph("Very high", body)],
    [Paragraph("Legumes", body),
     Paragraph("Lentils, beans, chickpeas, peanuts", body),
     Paragraph("High", body)],
    [Paragraph("Fruits", body),
     Paragraph("Citrus fruits, oranges, bananas", body),
     Paragraph("Moderate", body)],
    [Paragraph("Dairy / Eggs", body),
     Paragraph("Milk, eggs", body),
     Paragraph("Moderate", body)],
    [Paragraph("Fortified grains ★", body),
     Paragraph("Bread, cereals, pasta, rice (FDA-mandated 1998)", body),
     Paragraph("Synthetic folic acid added", body)],
]
story.append(make_table(src_header, src_rows,
    [CONTENT_W*0.28, CONTENT_W*0.45, CONTENT_W*0.27]))
story.append(Spacer(1,4))
story.append(key_box(
    "⚠️ <b>Remember:</b> Folate is <b>heat-labile</b>. Prolonged cooking destroys significant folate. "
    "Prefer lightly cooked or raw vegetables to preserve folate content.",
    bg=WARN_BG, border=WARN_BORDER))
story.append(Spacer(1, 8))

# ── 3. Biochemical Function ──────────────────────────────────────────────────
story.append(section("3.  Biochemical Functions – One-Carbon (1C) Metabolism"))
story.append(Spacer(1,4))
story.append(Paragraph(
    "THF acts as a <b>carrier of one-carbon units</b> (–CH₃, –CHO, –CH₂–) in key biosynthetic reactions:", body))
story.append(Spacer(1,4))

fn_header = [Paragraph("<b>Reaction</b>", body), Paragraph("<b>THF Form Used</b>", body),
             Paragraph("<b>Product / Significance</b>", body)]
fn_rows = [
    [Paragraph("Purine synthesis", body),
     Paragraph("N¹⁰-formyl THF", body),
     Paragraph("C-2 and C-8 of purine ring; essential for DNA/RNA", body)],
    [Paragraph("TMP synthesis (DNA)", body),
     Paragraph("N⁵,N¹⁰-methylene THF", body),
     Paragraph("Thymidine monophosphate (TMP/dTMP) for DNA; inhibited by methotrexate", body)],
    [Paragraph("Serine ↔ Glycine", body),
     Paragraph("N⁵,N¹⁰-methylene THF", body),
     Paragraph("Amino acid interconversion; main 1C donor", body)],
    [Paragraph("Methionine synthesis", body),
     Paragraph("N⁵-methyl THF", body),
     Paragraph("Homocysteine → Methionine (requires Vit B₁₂)", body)],
    [Paragraph("Histidine catabolism", body),
     Paragraph("THF accepts formimino group", body),
     Paragraph("FIGLU → Glutamate; FIGLU excreted in deficiency (diagnostic test)", body)],
]
story.append(make_table(fn_header, fn_rows,
    [CONTENT_W*0.25, CONTENT_W*0.28, CONTENT_W*0.47]))
story.append(Spacer(1, 6))

# one-carbon metabolism diagram
story += img_block("one_carbon_metabolism.png", 14,
    "Fig 2. Sources and utilisation of one-carbon substituted folates\n"
    "Source: Harper's Illustrated Biochemistry 32nd Ed.")
story.append(Spacer(1, 8))

# ── 4. RDA ───────────────────────────────────────────────────────────────────
story.append(section("4.  Daily Requirements (RDA)"))
story.append(Spacer(1,4))
rda_header = [Paragraph("<b>Group</b>", body), Paragraph("<b>RDA</b>", body),
              Paragraph("<b>Rationale</b>", body)]
rda_rows = [
    [Paragraph("Adult male & female", body), Paragraph("200–400 µg/day", body),
     Paragraph("Maintenance of normal 1C metabolism", body)],
    [Paragraph("Pregnancy", body), Paragraph("<b>400–800 µg/day</b>", body),
     Paragraph("Prevention of neural tube defects; increased cell division", body)],
    [Paragraph("Lactation", body), Paragraph("300–500 µg/day", body),
     Paragraph("Transfer in breast milk", body)],
    [Paragraph("Previous NTD pregnancy", body), Paragraph("<b>4 mg/day (4000 µg)</b>", body),
     Paragraph("High-risk; supplementation from 1 month pre-conception", body)],
]
story.append(make_table(rda_header, rda_rows,
    [CONTENT_W*0.3, CONTENT_W*0.22, CONTENT_W*0.48]))
story.append(Spacer(1, 8))

# ── 5. Deficiency – Causes ───────────────────────────────────────────────────
story.append(section("5.  Folic Acid Deficiency – Causes"))
story.append(Spacer(1,4))

cause_header = [Paragraph("<b>#</b>", body), Paragraph("<b>Cause</b>", body),
                Paragraph("<b>Examples / Mechanism</b>", body)]
cause_rows = [
    [Paragraph("1", body), Paragraph("Inadequate dietary intake", body),
     Paragraph("Poor diet, alcoholism, elderly, food insecurity", body)],
    [Paragraph("2", body), Paragraph("Increased demand", body),
     Paragraph("Pregnancy, lactation, haemolytic anaemias, malignancy, rapid growth", body)],
    [Paragraph("3", body), Paragraph("Malabsorption", body),
     Paragraph("Coeliac disease, Crohn's disease, tropical sprue (upper small intestine affected)", body)],
    [Paragraph("4", body), Paragraph("Drug-induced", body),
     Paragraph("Methotrexate / Trimethoprim → inhibit DHFR\n"
               "Phenytoin, phenobarbital → impair absorption\n"
               "Oral contraceptives → impair absorption\n"
               "Azathioprine, Zidovudine → inhibit DNA synthesis", body)],
    [Paragraph("5", body), Paragraph("Vitamin B₁₂ deficiency", body),
     Paragraph('"Folate Trap" – see Section 7', body)],
]
story.append(make_table(cause_header, cause_rows,
    [CONTENT_W*0.05, CONTENT_W*0.28, CONTENT_W*0.67]))
story.append(Spacer(1, 6))

# causes diagram
story += img_block("folate_deficiency_causes.png", 7,
    "Fig 3. Causes and consequences of folic acid depletion → Megaloblastic Anaemia\n"
    "Source: Lippincott Illustrated Reviews – Pharmacology")
story.append(Spacer(1, 8))

# ── 6. Deficiency – Symptoms ─────────────────────────────────────────────────
story.append(section("6.  Deficiency – Clinical Features (Symptoms)"))
story.append(Spacer(1,4))

story.append(Paragraph("<b>A. Megaloblastic (Macrocytic) Anaemia</b> — Hallmark", sub_hd))
story += bullet_list([
    "↓ TMP synthesis → ↓ DNA replication → RBC precursors cannot divide → <b>megaloblasts</b> accumulate in bone marrow",
    "<b>MCV > 100 fL</b> (macrocytic anaemia)",
    "<b>Hypersegmented neutrophils</b> on peripheral blood smear (≥5 lobes, or ≥1 six-lobed neutrophil)",
    "Symptoms: <b>fatigue, weakness, pallor, breathlessness, palpitations, dizziness</b>",
    "Onset is insidious (weeks to months)",
])
story.append(Spacer(1, 4))

# bone marrow image
story += img_block("bone_marrow.png", 10,
    "Fig 4. Bone marrow histology: Normal (left) vs. Megaloblastic/Folate-deficient (right)\n"
    "Source: Lippincott Illustrated Reviews – Biochemistry 8th Ed.")
story.append(Spacer(1, 6))

story.append(Paragraph("<b>B. Gastrointestinal Manifestations</b>", sub_hd))
story += bullet_list([
    "<b>Glossitis</b> – sore, smooth, red, beefy tongue",
    "<b>Stomatitis</b> – painful mouth ulcers",
    "Anorexia, nausea, diarrhoea",
    "(GI lining cells also divide rapidly → affected early)",
])
story.append(Spacer(1, 4))

story.append(Paragraph("<b>C. Neural Tube Defects (in pregnancy)</b>", sub_hd))
story += bullet_list([
    "<b>Spina bifida</b> – failure of spinal cord/vertebral arch closure",
    "<b>Anencephaly</b> – absence of brain development (lethal)",
    "Both are preventable with <b>periconceptional folic acid supplementation</b>",
])
story.append(Spacer(1, 4))

story.append(Paragraph("<b>D. Hyperhomocysteinaemia</b>", sub_hd))
story += bullet_list([
    "↓ Folate → ↓ remethylation of homocysteine → <b>↑ plasma homocysteine</b>",
    "Risk factor for: <b>atherosclerosis, coronary artery disease, thrombosis, hypertension</b>",
])
story.append(Spacer(1, 6))

story.append(key_box(
    "⭐ <b>KEY EXAM POINT – NO Neurological Symptoms:</b>  "
    "Unlike Vitamin B₁₂ deficiency, folic acid deficiency does <b>NOT</b> cause "
    "subacute combined degeneration of the spinal cord. There is no peripheral neuropathy, "
    "no ataxia, no dementia. This is a classic distinguishing feature in MCQs.",
    bg=GREEN_BG, border=colors.HexColor("#388e3c")))
story.append(Spacer(1, 8))

# ── 7. Folate Trap ───────────────────────────────────────────────────────────
story.append(section("7.  The 'Folate Trap' (Vitamin B₁₂ Connection)"))
story.append(Spacer(1,4))
story += bullet_list([
    "Circulating form of folate = <b>N⁵-methyl THF</b>",
    "To release THF, the methyl group must be transferred to homocysteine → methionine",
    "This reaction is catalysed by <b>methionine synthase</b>, which requires <b>Vitamin B₁₂</b> as cofactor",
    "In <b>B₁₂ deficiency</b> → methionine synthase is non-functional",
    "→ Folate remains trapped as N⁵-methyl THF and <b>cannot be converted back to free THF</b>",
    "→ <b>Functional folate deficiency</b> develops even with normal dietary folate intake",
    "→ Result: <b>Megaloblastic anaemia in Vitamin B₁₂ deficiency</b> (identical blood picture to folate deficiency)",
])
story.append(Spacer(1, 6))
story.append(key_box(
    "⚠️ <b>Clinical Warning:</b>  Treating a B₁₂-deficient patient with folic acid alone "
    "will correct the megaloblastic anaemia (masking the deficiency) but will allow "
    "<b>neurological damage to progress silently and irreversibly</b>.  "
    "Always rule out B₁₂ deficiency before prescribing folic acid alone.",
    bg=WARN_BG, border=WARN_BORDER))
story.append(Spacer(1, 8))

# ── 8. Drug Targets ──────────────────────────────────────────────────────────
story.append(section("8.  Drug Inhibitors of Folate Metabolism"))
story.append(Spacer(1,4))
drug_header = [Paragraph("<b>Drug</b>", body), Paragraph("<b>Target</b>", body),
               Paragraph("<b>Use</b>", body), Paragraph("<b>Note</b>", body)]
drug_rows = [
    [Paragraph("Methotrexate", body), Paragraph("Human DHFR", body),
     Paragraph("Cancer chemotherapy, RA, psoriasis", body),
     Paragraph("Leucovorin (folinic acid) used as rescue", body)],
    [Paragraph("Trimethoprim", body), Paragraph("Bacterial DHFR", body),
     Paragraph("Antibiotic (UTI, PCP)", body),
     Paragraph("Selective – higher affinity for bacterial enzyme", body)],
    [Paragraph("Pyrimethamine", body), Paragraph("Parasite DHFR", body),
     Paragraph("Antimalarial, toxoplasmosis", body),
     Paragraph("Combined with sulfadoxine", body)],
    [Paragraph("Leucovorin\n(folinic acid)", body), Paragraph("Bypasses DHFR", body),
     Paragraph("Rescue after methotrexate", body),
     Paragraph("5-formyl THF – directly active; does not need DHFR", body)],
]
story.append(make_table(drug_header, drug_rows,
    [CONTENT_W*0.2, CONTENT_W*0.2, CONTENT_W*0.3, CONTENT_W*0.3]))
story.append(Spacer(1, 8))

# ── 9. FIGLU Test ────────────────────────────────────────────────────────────
story.append(section("9.  FIGLU Excretion Test (Diagnostic Test for Folate Deficiency)"))
story.append(Spacer(1,4))
story += bullet_list([
    "Histidine is catabolised via <b>formiminoglutamate (FIGLU)</b>",
    "THF accepts the formimino group from FIGLU → Glutamate",
    "In folate deficiency → THF unavailable → <b>FIGLU accumulates and is excreted in urine</b>",
    "Test: Patient given oral histidine load → urine collected → FIGLU measured",
    "<b>Increased urinary FIGLU = positive test = folate deficiency</b>",
])
story.append(Spacer(1, 8))

# ── 10. Clinical Correlations ────────────────────────────────────────────────
story.append(section("10.  Clinical Correlations (Rafi-style)"))
story.append(Spacer(1,4))

cc_items = [
    ("<b>Folic acid in pregnancy:</b>",
     "All women of childbearing age should take 400 µg/day folic acid starting at least "
     "1 month BEFORE conception and through the first trimester. If a previous NTD-affected "
     "pregnancy: 4 mg/day."),
    ("<b>Alcohol and folate:</b>",
     "Alcoholism → ↓ dietary intake + ↓ intestinal absorption + ↓ hepatic storage + "
     "↑ renal excretion → commonest cause of folate deficiency in developed countries."),
    ("<b>Folate and cancer:</b>",
     "Low folate → impaired methylation of CpG islands in DNA → may increase risk of "
     "colorectal and other cancers. However, paradoxically, high folate may accelerate "
     "transformation of existing preneoplastic polyps."),
    ("<b>Masking B₁₂ deficiency:</b>",
     "Folic acid corrects megaloblastic anaemia in B₁₂ deficiency but does NOT prevent "
     "irreversible neurological damage (subacute combined degeneration). Always check B₁₂ first."),
    ("<b>Anticonvulsants and folate:</b>",
     "Phenytoin and phenobarbital interfere with folate absorption and may precipitate "
     "deficiency in epileptic patients on long-term therapy."),
]
for title_text, detail_text in cc_items:
    row_data = [[
        Paragraph(title_text, body),
        Paragraph(detail_text, body)
    ]]
    cc_tbl = Table(row_data, colWidths=[CONTENT_W*0.3, CONTENT_W*0.7])
    cc_tbl.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(0,-1), LIGHT_BLUE),
        ("BACKGROUND",   (1,0),(1,-1), WHITE),
        ("BOX",          (0,0),(-1,-1), 0.5, MID_BLUE),
        ("INNERGRID",    (0,0),(-1,-1), 0.3, GREY_LINE),
        ("LEFTPADDING",  (0,0),(-1,-1), 8),
        ("TOPPADDING",   (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("VALIGN",       (0,0),(-1,-1), "TOP"),
    ]))
    story.append(cc_tbl)
    story.append(Spacer(1, 3))

story.append(Spacer(1, 8))

# ── 11. Quick Revision Box ───────────────────────────────────────────────────
story.append(section("11.  Quick Revision – High-Yield MCQ Points"))
story.append(Spacer(1,4))
hiyield = [
    "Active form of folic acid = <b>Tetrahydrofolate (THF)</b>",
    "Enzyme that converts folic acid → THF = <b>Dihydrofolate reductase (DHFR)</b>",
    "One-carbon donor for TMP synthesis = <b>N⁵,N¹⁰-methylene THF</b>",
    "Folate deficiency → <b>Macrocytic megaloblastic anaemia</b> (MCV > 100)",
    "Blood smear finding = <b>Hypersegmented neutrophils</b>",
    "NO neurological symptoms in folate deficiency (unlike B₁₂)",
    "Folate trap = B₁₂ deficiency → folate stuck as N⁵-methyl THF",
    "Drug that inhibits DHFR = <b>Methotrexate</b>; antidote = <b>Leucovorin</b>",
    "Diagnostic test = <b>FIGLU excretion test</b> (↑ urinary FIGLU after histidine load)",
    "NTD prevention: <b>400 µg/day folic acid</b> periconceptionally",
    "Best dietary source = <b>green leafy vegetables</b>; destroyed by cooking",
]
for pt in hiyield:
    row_tbl = Table([[Paragraph(f"✔ {pt}", body)]], colWidths=[CONTENT_W])
    row_tbl.setStyle(TableStyle([
        ("LEFTPADDING",  (0,0),(-1,-1), 10),
        ("TOPPADDING",   (0,0),(-1,-1), 3),
        ("BOTTOMPADDING",(0,0),(-1,-1), 3),
        ("ROWBACKGROUNDS",(0,0),(-1,-1), [colors.HexColor("#f0f7ff"), WHITE]),
        ("BOX",          (0,0),(-1,-1), 0.3, GREY_LINE),
    ]))
    story.append(row_tbl)

story.append(Spacer(1, 10))
story.append(HRFlowable(width="100%", thickness=1, color=GREY_LINE))
story.append(Spacer(1, 4))
story.append(Paragraph(
    "Summary prepared from: Textbook of Biochemistry 5th Ed. – Rafi MD (Universities Press, NMC/CBME) | "
    "Lippincott Illustrated Reviews: Biochemistry 8th Ed. | Harper's Illustrated Biochemistry 32nd Ed.",
    footer_s))

# ── Build ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUT}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/folic-acid-pdf/generate_pdf.py'

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, Image, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from PIL import Image as PILImage
import os

ASSETS = "/tmp/workspace/median-nerve-pdf/assets"
OUT    = "/tmp/workspace/median-nerve-pdf/Median_Nerve_Summary.pdf"

W, H = A4
LM = RM = 1.8 * cm
CONTENT_W = W - LM - RM

# ── Palette ──────────────────────────────────────────────────────────────────
NAVY        = colors.HexColor("#0d2b4e")
DARK_BLUE   = colors.HexColor("#1a4a7a")
MID_BLUE    = colors.HexColor("#2e6da4")
LIGHT_BLUE  = colors.HexColor("#d6e8f7")
SKY         = colors.HexColor("#eaf4fb")
ORANGE      = colors.HexColor("#e07b00")
GOLD        = colors.HexColor("#ffd580")
WARN_BG     = colors.HexColor("#fff8e1")
WARN_BORDER = colors.HexColor("#f9a825")
GREEN_BG    = colors.HexColor("#e8f5e9")
GREEN_BD    = colors.HexColor("#388e3c")
RED_BG      = colors.HexColor("#fce4ec")
RED_BD      = colors.HexColor("#c62828")
GREY        = colors.HexColor("#cccccc")
DARK_GREY   = colors.HexColor("#444444")
WHITE       = colors.white
BLACK       = colors.black

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

cover_title  = S("CoverTitle", fontSize=30, textColor=WHITE,
                 fontName="Helvetica-Bold", alignment=TA_CENTER, leading=36)
cover_sub    = S("CoverSub",   fontSize=14, textColor=GOLD,
                 fontName="Helvetica-BoldOblique", alignment=TA_CENTER, leading=20)
cover_meta   = S("CoverMeta",  fontSize=9.5, textColor=colors.HexColor("#b0c8e8"),
                 fontName="Helvetica", alignment=TA_CENTER, leading=14)

sec_hd_s = S("SecHd", fontSize=12, textColor=WHITE,
              fontName="Helvetica-Bold", leading=16)
sub_hd_s = S("SubHd", fontSize=10.5, textColor=DARK_BLUE,
              fontName="Helvetica-Bold", leading=15, spaceBefore=6, spaceAfter=2)
body_s   = S("Body",  fontSize=9.5,  textColor=BLACK,
              fontName="Helvetica",  leading=14, spaceAfter=2, alignment=TA_JUSTIFY)
bullet_s = S("Bul",   fontSize=9.5,  textColor=BLACK,
              fontName="Helvetica",  leading=14, spaceAfter=2,
              leftIndent=14, firstLineIndent=-10)
caption_s= S("Cap",   fontSize=8,    textColor=DARK_GREY,
              fontName="Helvetica-Oblique", alignment=TA_CENTER, leading=11, spaceAfter=5)
footer_s = S("Foot",  fontSize=7.5,  textColor=colors.HexColor("#888888"),
              fontName="Helvetica", alignment=TA_CENTER)
tag_s    = S("Tag",   fontSize=8.5,  textColor=WHITE,
              fontName="Helvetica-Bold", alignment=TA_CENTER)
key_s    = S("Key",   fontSize=9,    textColor=colors.HexColor("#1a3a5c"),
              fontName="Helvetica-Bold", leading=13, alignment=TA_JUSTIFY)

# ── Helpers ──────────────────────────────────────────────────────────────────
def section(title, bg=DARK_BLUE):
    tbl = Table([[Paragraph(title, sec_hd_s)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), bg),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
    ]))
    return tbl

def box(text, bg=SKY, border=MID_BLUE, style=None):
    st = style or body_s
    tbl = Table([[Paragraph(text, st)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), bg),
        ("BOX",           (0,0),(-1,-1), 1,   border),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("RIGHTPADDING",  (0,0),(-1,-1), 10),
        ("TOPPADDING",    (0,0),(-1,-1), 6),
        ("BOTTOMPADDING", (0,0),(-1,-1), 6),
    ]))
    return tbl

def bullets(items, style=bullet_s):
    return [Paragraph(f"• {i}", style) for i in items]

def img(fname, w_cm, cap=""):
    path = os.path.join(ASSETS, fname)
    try:
        with PILImage.open(path) as p:
            iw, ih = p.size
        tw = w_cm * cm
        th = tw * ih / iw
        im = Image(path, width=tw, height=th)
        im.hAlign = "CENTER"
        elems = [im]
        if cap:
            elems.append(Paragraph(cap, caption_s))
        return elems
    except Exception as e:
        return [Paragraph(f"[Image: {fname}] ({e})", caption_s)]

def two_col_img(f1, w1, cap1, f2, w2, cap2):
    """Side-by-side images in a two-column table."""
    col1 = img(f1, w1, cap1)
    col2 = img(f2, w2, cap2)
    from reportlab.platypus import KeepInFrame
    half = CONTENT_W / 2 - 4
    tbl = Table([[col1, col2]], colWidths=[half, half])
    tbl.setStyle(TableStyle([
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("ALIGN",         (0,0),(-1,-1), "CENTER"),
        ("LEFTPADDING",   (0,0),(-1,-1), 2),
        ("RIGHTPADDING",  (0,0),(-1,-1), 2),
    ]))
    return tbl

def make_table(header, rows, widths, hbg=DARK_BLUE, alt=LIGHT_BLUE):
    data = [header] + rows
    tbl  = Table(data, colWidths=widths, repeatRows=1)
    ts = [
        ("BACKGROUND",    (0,0),(-1, 0), hbg),
        ("TEXTCOLOR",     (0,0),(-1, 0), WHITE),
        ("FONTNAME",      (0,0),(-1, 0), "Helvetica-Bold"),
        ("FONTSIZE",      (0,0),(-1,-1), 8.5),
        ("FONTNAME",      (0,1),(-1,-1), "Helvetica"),
        ("GRID",          (0,0),(-1,-1), 0.4, GREY),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [WHITE, alt]),
        ("LEFTPADDING",   (0,0),(-1,-1), 6),
        ("RIGHTPADDING",  (0,0),(-1,-1), 6),
        ("TOPPADDING",    (0,0),(-1,-1), 4),
        ("BOTTOMPADDING", (0,0),(-1,-1), 4),
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ]
    tbl.setStyle(TableStyle(ts))
    return tbl

def sp(h=6): return Spacer(1, h)
def hr(): return HRFlowable(width="100%", thickness=0.5, color=GREY, spaceAfter=4)

# ── Document ─────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUT, pagesize=A4,
    leftMargin=LM, rightMargin=RM,
    topMargin=1.8*cm, bottomMargin=1.8*cm,
    title="Median Nerve – Anatomy Summary",
    author="Vishram Singh Style | Gray's Anatomy for Students"
)

story = []

# ═══════════════════════════════════════════════════════════════════
# COVER
# ═══════════════════════════════════════════════════════════════════
def cover():
    elems = []
    # Title block
    cv = Table(
        [[Paragraph("MEDIAN NERVE", cover_title)],
         [Paragraph("Complete Anatomy Summary", cover_sub)],
         [Paragraph("Vishram Singh Style  •  Regional Anatomy Format", cover_meta)],
         [Paragraph("Based on: Gray's Anatomy for Students  |  Bradley & Daroff's Neurology", cover_meta)]],
        colWidths=[CONTENT_W])
    cv.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), NAVY),
        ("LEFTPADDING",   (0,0),(-1,-1), 20),
        ("RIGHTPADDING",  (0,0),(-1,-1), 20),
        ("TOPPADDING",    (0,0),(0,0),   28),
        ("BOTTOMPADDING", (0,3),(-1,-1), 28),
        ("TOPPADDING",    (0,1),(-1,-1),  5),
        ("BOTTOMPADDING", (0,0),(-1,2),   5),
    ]))
    elems.append(cv)
    elems.append(sp(10))

    # Quick-ref strip
    qr = [
        [Paragraph("<b>FEATURE</b>", tag_s), Paragraph("<b>DETAIL</b>", tag_s)],
        [Paragraph("Root value", body_s),    Paragraph("<b>C6, C7, C8, T1</b>", body_s)],
        [Paragraph("Origin", body_s),        Paragraph("Lateral + Medial cords of brachial plexus", body_s)],
        [Paragraph("Type", body_s),          Paragraph("Mixed (motor + sensory)", body_s)],
        [Paragraph("Branches in arm", body_s), Paragraph("<b>None</b> (occasionally tiny branch to pronator teres)", body_s)],
        [Paragraph("Key branch in forearm", body_s), Paragraph("Anterior Interosseous Nerve (AIN)", body_s)],
        [Paragraph("Enters palm via", body_s), Paragraph("<b>Carpal tunnel</b> (deep to flexor retinaculum)", body_s)],
        [Paragraph("Intrinsic muscles (LOAF)", body_s), Paragraph("Lumbricals 1&2, Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis", body_s)],
        [Paragraph("High injury deformity", body_s), Paragraph("<b>Hand of Benediction</b>", body_s)],
        [Paragraph("Low injury deformity", body_s),  Paragraph("<b>Ape Hand</b>", body_s)],
    ]
    qr_tbl = Table(qr, colWidths=[CONTENT_W*0.35, CONTENT_W*0.65])
    qr_tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1, 0), ORANGE),
        ("TEXTCOLOR",     (0,0),(-1, 0), WHITE),
        ("FONTNAME",      (0,0),(-1, 0), "Helvetica-Bold"),
        ("FONTSIZE",      (0,0),(-1,-1),  8.5),
        ("FONTNAME",      (0,1),(-1,-1), "Helvetica"),
        ("GRID",          (0,0),(-1,-1),  0.4, GREY),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [WHITE, SKY]),
        ("LEFTPADDING",   (0,0),(-1,-1),  7),
        ("TOPPADDING",    (0,0),(-1,-1),  4),
        ("BOTTOMPADDING", (0,0),(-1,-1),  4),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
    ]))
    elems.append(qr_tbl)
    elems.append(sp(10))

    # side-by-side diagrams on cover
    tbl = two_col_img(
        "forearm_nerves.png", 7.5,
        "Fig 1. Nerves of the Anterior Forearm\n(Gray's Anatomy for Students)",
        "hand_median.png", 7.5,
        "Fig 2. Median Nerve Branches in the Hand – Palmar & Dorsal cutaneous distribution\n(Gray's Anatomy for Students)"
    )
    elems.append(tbl)
    elems.append(PageBreak())
    return elems

story += cover()

# ═══════════════════════════════════════════════════════════════════
# 1. ROOT VALUE & ORIGIN
# ═══════════════════════════════════════════════════════════════════
story.append(section("1.  Root Value & Origin"))
story.append(sp(5))
story.append(Paragraph("<b>Root Value:</b>  C6, C7, C8, T1", body_s))
story.append(sp(4))
origin_rows = [
    [Paragraph("<b>Root</b>", body_s),      Paragraph("<b>Cord</b>", body_s),       Paragraph("<b>Contribution</b>", body_s)],
    [Paragraph("C6, C7", body_s),           Paragraph("Lateral cord", body_s),      Paragraph("Lateral root of median nerve", body_s)],
    [Paragraph("C8, T1", body_s),           Paragraph("Medial cord", body_s),       Paragraph("Medial root of median nerve", body_s)],
]
story.append(make_table(origin_rows[0:1], origin_rows[1:],
    [CONTENT_W*0.2, CONTENT_W*0.3, CONTENT_W*0.5]))
story.append(sp(5))
story.append(box(
    "⚠️  The two roots unite in front of the <b>3rd part of the axillary artery</b>, "
    "forming an inverted 'V' or 'M' shape. This is a common exam question.",
    bg=WARN_BG, border=WARN_BORDER))
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 2. COURSE & RELATIONS
# ═══════════════════════════════════════════════════════════════════
story.append(section("2.  Course & Relations (Region by Region)"))
story.append(sp(5))

# Axilla
story.append(Paragraph("<b>A. In the Axilla</b>", sub_hd_s))
story += bullets([
    "Formed in front of the axillary artery",
    "Runs along the lateral wall of the axilla",
    "<b>No branches</b> in the axilla",
])
story.append(sp(6))

# Arm
story.append(Paragraph("<b>B. In the Arm</b>", sub_hd_s))
story += bullets([
    "Enters the arm at the inferior margin of <b>teres major</b>",
    "Runs in the <b>anterior compartment</b> along the medial side",
    "Closely related to the <b>brachial artery</b> throughout:",
])
rel_rows = [
    [Paragraph("<b>Region</b>", body_s),     Paragraph("<b>Relation to Brachial Artery</b>", body_s)],
    [Paragraph("Proximal arm", body_s),      Paragraph("Lateral to the brachial artery", body_s)],
    [Paragraph("Distal arm / elbow", body_s), Paragraph("Crosses anterior → lies medial to the artery", body_s)],
]
story.append(make_table(rel_rows[0:1], rel_rows[1:],
    [CONTENT_W*0.35, CONTENT_W*0.65]))
story += bullets([
    "Passes <b>anterior to the elbow joint</b>",
    "<b>No major branches in the arm</b> (occasionally small branch to pronator teres just proximal to elbow)",
])
story.append(sp(6))

# Forearm
story.append(Paragraph("<b>C. In the Forearm (Anterior Compartment)</b>", sub_hd_s))
story += bullets([
    "Enters forearm by passing <b>between two heads of pronator teres</b> (humeral & ulnar heads)",
    "Passes deep to the fibrous arch between the humero-ulnar and radial heads of <b>FDS</b>",
    "Runs distally in fascia on the <b>deep surface of FDS</b>",
    "Just proximal to wrist: moves laterally, becomes superficial between <b>palmaris longus (medial)</b> and <b>FCR (lateral)</b>",
    "Enters palm through <b>carpal tunnel</b>, deep to flexor retinaculum",
])
story.append(sp(6))

# Wrist
story.append(Paragraph("<b>D. At the Wrist / Carpal Tunnel</b>", sub_hd_s))
story += bullets([
    "Passes through carpal tunnel deep to flexor retinaculum",
    "<b>Palmar cutaneous branch</b> arises just proximal to the retinaculum and passes <b>superficial</b> to it",
    "Therefore palmar cutaneous branch is <b>SPARED in carpal tunnel syndrome</b>",
])
story.append(sp(6))

# Hand
story.append(Paragraph("<b>E. In the Palm / Hand</b>", sub_hd_s))
story += bullets([
    "Emerges distal to flexor retinaculum",
    "Divides into <b>recurrent (thenar) branch</b> and <b>palmar digital branches</b>",
    "Palmar digital nerves pass deep to palmar aponeurosis and superficial palmar arch",
])
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 3. BRANCHES
# ═══════════════════════════════════════════════════════════════════
story.append(section("3.  Branches"))
story.append(sp(5))

story.append(Paragraph("<b>A. In the Forearm</b>", sub_hd_s))
br_rows = [
    [Paragraph("<b>Branch</b>", body_s), Paragraph("<b>Muscles / Structures Supplied</b>", body_s)],
    [Paragraph("Muscular branches\n(near elbow)", body_s),
     Paragraph("Pronator teres, Flexor carpi radialis (FCR), Palmaris longus, "
               "Flexor digitorum superficialis (FDS) – all 4 fingers", body_s)],
    [Paragraph("<b>Anterior Interosseous\nNerve (AIN)</b>\n[largest branch]", body_s),
     Paragraph("• Flexor pollicis longus (FPL)\n"
               "• Lateral half of FDP (index + middle fingers)\n"
               "• Pronator quadratus\n"
               "• Articular branches to distal radio-ulnar & wrist joints", body_s)],
    [Paragraph("Palmar cutaneous branch\n(just proximal to wrist)", body_s),
     Paragraph("Skin over base and central palm\n"
               "(passes SUPERFICIAL to flexor retinaculum → spared in CTS)", body_s)],
]
story.append(make_table(br_rows[0:1], br_rows[1:],
    [CONTENT_W*0.3, CONTENT_W*0.7]))
story.append(sp(8))

story.append(Paragraph("<b>B. In the Hand</b>", sub_hd_s))
hand_rows = [
    [Paragraph("<b>Branch</b>", body_s), Paragraph("<b>Course</b>", body_s), Paragraph("<b>Supply</b>", body_s)],
    [Paragraph("<b>Recurrent (thenar) branch</b>", body_s),
     Paragraph("Curves laterally around distal margin of retinaculum, passes proximally over FPB", body_s),
     Paragraph("Abductor pollicis brevis (APB)\nOpponens pollicis\nFlexor pollicis brevis – superficial head (FPB)", body_s)],
    [Paragraph("<b>Palmar digital nerves</b>", body_s),
     Paragraph("Cross palm deep to palmar aponeurosis and superficial palmar arch", body_s),
     Paragraph("Skin: palmar surface of lateral 3½ digits + dorsal nail beds of same\n"
               "Lateral two lumbrical muscles (1st & 2nd)", body_s)],
]
story.append(make_table(hand_rows[0:1], hand_rows[1:],
    [CONTENT_W*0.25, CONTENT_W*0.37, CONTENT_W*0.38]))
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# FOREARM DIAGRAM (full width)
# ═══════════════════════════════════════════════════════════════════
story.append(section("Diagram 1 – Nerves of the Anterior Forearm", bg=MID_BLUE))
story.append(sp(6))
story += img("forearm_nerves.png", 10,
    "Fig 1. Median nerve in the forearm: origin between heads of pronator teres, course of AIN, palmar cutaneous branch\n"
    "Source: Gray's Anatomy for Students")
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 4. MOTOR SUPPLY
# ═══════════════════════════════════════════════════════════════════
story.append(section("4.  Motor Supply"))
story.append(sp(5))

story.append(Paragraph("<b>A. Forearm Muscles</b>  (all anterior compartment EXCEPT FCU and medial FDP)", sub_hd_s))
fm_rows = [
    [Paragraph("<b>Layer</b>", body_s),     Paragraph("<b>Muscle</b>", body_s),         Paragraph("<b>Action</b>", body_s)],
    [Paragraph("Superficial", body_s),      Paragraph("Pronator teres", body_s),         Paragraph("Pronation of forearm", body_s)],
    [Paragraph("Superficial", body_s),      Paragraph("Flexor carpi radialis (FCR)", body_s), Paragraph("Wrist flexion + radial deviation", body_s)],
    [Paragraph("Superficial", body_s),      Paragraph("Palmaris longus", body_s),        Paragraph("Wrist flexion (absent in ~14%)", body_s)],
    [Paragraph("Intermediate", body_s),     Paragraph("FDS – all 4 fingers", body_s),   Paragraph("Flex PIP joints", body_s)],
    [Paragraph("Deep (via AIN)", body_s),   Paragraph("Flexor pollicis longus (FPL)", body_s), Paragraph("Flex IP joint of thumb", body_s)],
    [Paragraph("Deep (via AIN)", body_s),   Paragraph("FDP – lateral half (index + middle)", body_s), Paragraph("Flex DIP joints of index & middle", body_s)],
    [Paragraph("Deep (via AIN)", body_s),   Paragraph("Pronator quadratus", body_s),    Paragraph("Pronation of forearm (main pronator)", body_s)],
]
story.append(make_table(fm_rows[0:1], fm_rows[1:],
    [CONTENT_W*0.22, CONTENT_W*0.38, CONTENT_W*0.4]))
story.append(sp(6))

story.append(Paragraph("<b>B. Hand Muscles – LOAF</b>  (mnemonic)", sub_hd_s))
story.append(box(
    "  <b>L</b> – Lateral two Lumbricals (1st & 2nd) → flex MCP, extend IP joints of index & middle\n"
    "  <b>O</b> – Opponens pollicis → opposes thumb (draws it across palm)\n"
    "  <b>A</b> – Abductor pollicis brevis (APB) → abducts thumb at right angles to palm\n"
    "  <b>F</b> – Flexor pollicis brevis (FPB) – superficial head → flexes MCP joint of thumb",
    bg=LIGHT_BLUE, border=MID_BLUE))
story.append(sp(6))
story.append(box(
    "⚠️ <b>NOT supplied by median nerve:</b>  "
    "Flexor carpi ulnaris (FCU) and medial half of FDP (ring & little fingers) → <b>Ulnar nerve</b>",
    bg=WARN_BG, border=WARN_BORDER))
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 5. SENSORY SUPPLY
# ═══════════════════════════════════════════════════════════════════
story.append(section("5.  Sensory Supply"))
story.append(sp(5))
story += bullets([
    "<b>Palmar surface</b> of lateral 3½ digits (thumb, index, middle, lateral half of ring finger)",
    "<b>Dorsal surface</b> of distal phalanges (nail beds) of same lateral 3½ digits",
    "<b>Lateral (radial) palm</b> – via palmar cutaneous branch (arising above wrist, <b>NOT via carpal tunnel</b>)",
])
story.append(sp(5))
story.append(box(
    "⭐  The median nerve is called the <b>'Eye of the Hand'</b> or <b>'Nerve of Precision Grip'</b> — "
    "it provides the most important sensory supply for fine touch, two-point discrimination, "
    "and positioning during pinch.",
    bg=GREEN_BG, border=GREEN_BD, style=key_s))
story.append(sp(10))

# HAND DIAGRAM
story.append(section("Diagram 2 – Median Nerve in the Hand & Cutaneous Distribution", bg=MID_BLUE))
story.append(sp(6))
story += img("hand_median.png", 13,
    "Fig 2. Median nerve branches in the hand: recurrent thenar branch, digital nerves, lumbrical supply.\n"
    "Cutaneous distribution (green) shown on palmar and dorsal views.\n"
    "Source: Gray's Anatomy for Students")
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 6. APPLIED ANATOMY
# ═══════════════════════════════════════════════════════════════════
story.append(section("6.  Applied Anatomy – Injuries & Clinical Conditions"))
story.append(sp(5))

# Injury levels table
story.append(Paragraph("<b>A. Effects of Injury at Different Levels</b>", sub_hd_s))
inj_rows = [
    [Paragraph("<b>Level</b>", body_s), Paragraph("<b>Motor Loss</b>", body_s),
     Paragraph("<b>Sensory Loss</b>", body_s), Paragraph("<b>Deformity</b>", body_s)],
    [Paragraph("Above elbow\n(high)", body_s),
     Paragraph("All forearm flexors (except FCU + medial FDP) + LOAF muscles", body_s),
     Paragraph("Lateral 3½ digits + lateral palm", body_s),
     Paragraph("<b>Hand of\nBenediction</b>", body_s)],
    [Paragraph("At/above wrist\n(low)", body_s),
     Paragraph("LOAF muscles only (forearm muscles intact)", body_s),
     Paragraph("Lateral 3½ digits + lateral palm", body_s),
     Paragraph("<b>Ape Hand</b>", body_s)],
    [Paragraph("Carpal tunnel\n(CTS)", body_s),
     Paragraph("LOAF muscles (late); thenar wasting", body_s),
     Paragraph("Lateral 3½ digits ONLY\n(central palm SPARED)", body_s),
     Paragraph("Thenar\nwasting", body_s)],
    [Paragraph("Anterior\ninterosseous\nnerve (AIN)", body_s),
     Paragraph("FPL + lateral FDP (index, middle) + pronator quadratus", body_s),
     Paragraph("<b>No sensory loss</b>\n(purely motor nerve)", body_s),
     Paragraph("Cannot make\n'OK sign'", body_s)],
]
story.append(make_table(inj_rows[0:1], inj_rows[1:],
    [CONTENT_W*0.17, CONTENT_W*0.33, CONTENT_W*0.28, CONTENT_W*0.22]))
story.append(sp(8))

# Hand of benediction
story.append(Paragraph("<b>B. Hand of Benediction (High Median Nerve Injury)</b>", sub_hd_s))
story += bullets([
    "Seen when patient attempts to make a fist after a <b>high (above elbow)</b> injury",
    "Index and middle fingers remain <b>extended</b> – FDP to these fingers is paralysed",
    "Ring and little fingers flex normally – their FDP is supplied by the ulnar nerve (intact)",
    "Resembles the gesture of a bishop giving a blessing",
    "Common cause: supracondylar fracture of humerus in children",
])
story.append(sp(8))

# Ape hand
story.append(Paragraph("<b>C. Ape Hand Deformity (Low Median Nerve Injury)</b>", sub_hd_s))
story += bullets([
    "Seen in <b>low (at wrist)</b> injury – forearm muscles are intact",
    "Thenar muscles paralysed → thumb adducted, falls back in the plane of the palm",
    "Cannot oppose thumb (opponens pollicis lost)",
    "Thenar eminence flattened/wasted",
    "No benediction posture because FDP (index, middle) still intact",
])
story.append(sp(6))

# Side-by-side clinical photos
tbl2 = two_col_img(
    "ape_hand.jpg", 6.5,
    "Fig 3. Ape hand deformity – thenar wasting and adducted thumb\n(low/wrist-level median nerve injury)",
    "carpal_tunnel.jpg", 6.5,
    "Fig 4. Surface anatomy of carpal tunnel – median nerve between\npalmaris longus and FCR tendons at wrist"
)
story.append(tbl2)
story.append(sp(8))

# CTS
story.append(Paragraph("<b>D. Carpal Tunnel Syndrome (CTS)</b>  – Commonest Entrapment Neuropathy", sub_hd_s))
story += bullets([
    "Median nerve compressed under <b>flexor retinaculum</b> at the wrist",
    "<b>Causes:</b> pregnancy, hypothyroidism, rheumatoid arthritis, acromegaly, obesity, repetitive wrist use, diabetes",
    "<b>Features:</b> night pain, tingling/numbness in lateral 3½ digits, thenar wasting (late)",
    "<b>Central palm sensation PRESERVED</b> – palmar cutaneous branch passes superficial to retinaculum",
    "<b>Tinel's sign:</b> tapping over carpal tunnel reproduces tingling distally",
    "<b>Phalen's test:</b> sustained wrist flexion (60 sec) reproduces symptoms",
    "<b>Treatment:</b> wrist splinting, corticosteroid injection, surgical carpal tunnel release",
])
story.append(sp(8))

# AIN palsy
story.append(Paragraph("<b>E. Anterior Interosseous Nerve (AIN) Palsy</b>", sub_hd_s))
story += bullets([
    "AIN is a <b>purely motor</b> branch – no sensory loss",
    "Supplies: FPL, lateral FDP (index, middle), pronator quadratus",
    "Cannot flex IP joint of thumb and DIP joint of index finger",
    "Cannot make the <b>'OK sign'</b> (pinch test positive)",
    "Causes: forearm fractures, penetrating injuries, tight cast, spontaneous (Parsonage-Turner)",
])
story.append(sp(8))

# Pronator syndrome
story.append(Paragraph("<b>F. Pronator Syndrome</b>", sub_hd_s))
story += bullets([
    "Median nerve compressed at <b>pronator teres</b> in the forearm",
    "Unlike CTS: <b>central palm IS affected</b> (palmar cutaneous branch arises above the compression site)",
    "Aching forearm pain worsened by resisted pronation",
    "Tinel's sign over pronator teres (not carpal tunnel)",
])
story.append(sp(10))

# ═══════════════════════════════════════════════════════════════════
# 7. QUICK REVISION
# ═══════════════════════════════════════════════════════════════════
story.append(section("7.  Quick Revision – High-Yield Exam Points"))
story.append(sp(5))

hiyield = [
    "Root value: <b>C6, C7, C8, T1</b> – formed from lateral + medial cords of brachial plexus",
    "Only nerve to enter palm through the <b>carpal tunnel</b> (deep to flexor retinaculum)",
    "<b>No branches in axilla or arm</b> (except sometimes a tiny branch to pronator teres)",
    "AIN = largest branch; purely motor; supplies <b>FPL, lateral FDP, pronator quadratus</b>",
    "Palmar cutaneous branch = spared in CTS (arises above wrist, passes superficial to retinaculum)",
    "LOAF = <b>L</b>umbricals 1&2, <b>O</b>pponens pollicis, <b>A</b>bductor pollicis brevis, <b>F</b>lexor pollicis brevis",
    "High injury → <b>Hand of Benediction</b> (index + middle extended on making fist)",
    "Low injury (wrist) → <b>Ape Hand</b> (thumb adducted, thenar wasted, no opposition)",
    "CTS: central palm OK + thenar wasting + positive Tinel's + positive Phalen's",
    "AIN palsy: cannot make OK sign; <b>no sensory loss</b>",
    "'<b>Eye of the hand</b>' – most important sensory nerve for fine touch and precision pinch",
    "Cannot supply: <b>FCU</b> and <b>medial FDP</b> (ring + little) → these are ulnar nerve",
]
for i, pt in enumerate(hiyield):
    row_bg = SKY if i % 2 == 0 else WHITE
    tbl = Table([[Paragraph(f"✔  {pt}", body_s)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), row_bg),
        ("BOX",           (0,0),(-1,-1), 0.3, GREY),
        ("LEFTPADDING",   (0,0),(-1,-1), 10),
        ("TOPPADDING",    (0,0),(-1,-1),  3),
        ("BOTTOMPADDING", (0,0),(-1,-1),  3),
    ]))
    story.append(tbl)

story.append(sp(10))
story.append(hr())
story.append(sp(4))
story.append(Paragraph(
    "Sources: Gray's Anatomy for Students (Elsevier)  |  Bradley & Daroff's Neurology in Clinical Practice  |  "
    "Vishram Singh – Textbook of Clinical Anatomy (Regional & Applied)",
    footer_s))

# ── Build ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUT}")