Complete Anatomy of the Liver

ls /home/daytona/workspace/ && python3 -c "import weasyprint; print('weasyprint …

mkdir -p /home/daytona/workspace/liver-anatomy-pdf && python3 -c " import urllib…

~/liver-anatomy-pdf/generate_pdf.py

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

OUTPUT = "/home/daytona/workspace/liver-anatomy-pdf/Liver_Anatomy_Complete.pdf"
IMG_DIR = "/home/daytona/workspace/liver-anatomy-pdf"

# ── Page setup ────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2.5*cm, bottomMargin=2.5*cm,
    title="Complete Anatomy of the Liver",
    author="Orris Medical Education",
    subject="Liver Anatomy with Clinical Correlates"
)

W, H = A4
CONTENT_W = W - 4*cm

# ── Colour palette ─────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3A5C")
MED_BLUE    = colors.HexColor("#2C6FAC")
LIGHT_BLUE  = colors.HexColor("#EBF4FF")
ACCENT_RED  = colors.HexColor("#C0392B")
ACCENT_GOLD = colors.HexColor("#D4A017")
CLINICAL_BG = colors.HexColor("#FFF8E7")
CLINICAL_BORDER = colors.HexColor("#E67E22")
TABLE_HEADER = colors.HexColor("#1A3A5C")
TABLE_ROW_ALT = colors.HexColor("#F0F6FF")
GREY_LINE   = colors.HexColor("#CCCCCC")
TEXT_DARK   = colors.HexColor("#1A1A1A")

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

title_style = ParagraphStyle("DocTitle",
    fontName="Helvetica-Bold", fontSize=26, textColor=DARK_BLUE,
    alignment=TA_CENTER, spaceAfter=6, leading=32)

subtitle_style = ParagraphStyle("DocSubtitle",
    fontName="Helvetica-Oblique", fontSize=13, textColor=MED_BLUE,
    alignment=TA_CENTER, spaceAfter=4, leading=18)

sources_style = ParagraphStyle("Sources",
    fontName="Helvetica", fontSize=8, textColor=colors.HexColor("#555555"),
    alignment=TA_CENTER, spaceAfter=2, leading=11)

h1_style = ParagraphStyle("H1",
    fontName="Helvetica-Bold", fontSize=16, textColor=DARK_BLUE,
    spaceBefore=18, spaceAfter=6, leading=20,
    borderPad=4)

h2_style = ParagraphStyle("H2",
    fontName="Helvetica-Bold", fontSize=13, textColor=MED_BLUE,
    spaceBefore=12, spaceAfter=4, leading=16)

h3_style = ParagraphStyle("H3",
    fontName="Helvetica-BoldOblique", fontSize=11, textColor=DARK_BLUE,
    spaceBefore=8, spaceAfter=3, leading=14)

body_style = ParagraphStyle("Body",
    fontName="Helvetica", fontSize=10, textColor=TEXT_DARK,
    spaceBefore=3, spaceAfter=3, leading=15, alignment=TA_JUSTIFY)

bullet_style = ParagraphStyle("Bullet",
    fontName="Helvetica", fontSize=10, textColor=TEXT_DARK,
    spaceBefore=2, spaceAfter=2, leading=14,
    leftIndent=16, firstLineIndent=-10)

clinical_title_style = ParagraphStyle("ClinTitle",
    fontName="Helvetica-Bold", fontSize=10, textColor=CLINICAL_BORDER,
    spaceBefore=2, spaceAfter=2, leading=14)

clinical_body_style = ParagraphStyle("ClinBody",
    fontName="Helvetica", fontSize=10, textColor=TEXT_DARK,
    spaceBefore=2, spaceAfter=2, leading=14, alignment=TA_JUSTIFY)

caption_style = ParagraphStyle("Caption",
    fontName="Helvetica-Oblique", fontSize=8.5, textColor=colors.HexColor("#444444"),
    alignment=TA_CENTER, spaceBefore=3, spaceAfter=6, leading=12)

# ── Helper functions ───────────────────────────────────────────────────────────

def section_header(num, text):
    """Returns a numbered section heading with blue left-border effect."""
    return [
        HRFlowable(width="100%", thickness=2, color=DARK_BLUE, spaceAfter=4),
        Paragraph(f"{num}. {text}", h1_style),
    ]

def sub_header(text):
    return Paragraph(text, h2_style)

def sub_sub_header(text):
    return Paragraph(text, h3_style)

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

def bullet(text):
    return Paragraph(f"• {text}", bullet_style)

def spacer(h=0.3):
    return Spacer(1, h*cm)

def clinical_box(title, text):
    """Orange-bordered clinical correlate box."""
    content = [
        Paragraph(f"🩺 Clinical Correlate: {title}", clinical_title_style),
        Paragraph(text, clinical_body_style),
    ]
    t = Table([[content]], colWidths=[CONTENT_W - 1*cm])
    t.setStyle(TableStyle([
        ('BACKGROUND', (0,0), (-1,-1), CLINICAL_BG),
        ('BOX', (0,0), (-1,-1), 1.5, CLINICAL_BORDER),
        ('LEFTPADDING', (0,0), (-1,-1), 10),
        ('RIGHTPADDING', (0,0), (-1,-1), 10),
        ('TOPPADDING', (0,0), (-1,-1), 8),
        ('BOTTOMPADDING', (0,0), (-1,-1), 8),
        ('ROUNDEDCORNERS', [4, 4, 4, 4]),
    ]))
    return [spacer(0.2), t, spacer(0.2)]

def make_table(headers, rows, col_widths=None):
    """Styled data table with alternating rows."""
    if col_widths is None:
        col_widths = [CONTENT_W / len(headers)] * len(headers)
    data = [[Paragraph(f"<b><font color='white'>{h}</font></b>", ParagraphStyle(
                'th', fontName='Helvetica-Bold', fontSize=9, textColor=colors.white,
                alignment=TA_CENTER, leading=12)) for h in headers]]
    for i, row in enumerate(rows):
        data.append([Paragraph(str(cell), ParagraphStyle(
            'td', fontName='Helvetica', fontSize=9, textColor=TEXT_DARK,
            leading=13, spaceBefore=1)) for cell in row])
    t = Table(data, colWidths=col_widths)
    style = [
        ('BACKGROUND', (0,0), (-1,0), TABLE_HEADER),
        ('GRID', (0,0), (-1,-1), 0.5, GREY_LINE),
        ('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'),
    ]
    for i in range(1, len(data)):
        if i % 2 == 0:
            style.append(('BACKGROUND', (0,i), (-1,i), TABLE_ROW_ALT))
    t.setStyle(TableStyle(style))
    return [spacer(0.2), t, spacer(0.3)]

def img_block(filename, caption, max_w=None, max_h=8*cm):
    """Image with caption, scaled to fit."""
    path = os.path.join(IMG_DIR, filename)
    if not os.path.exists(path):
        return []
    from PIL import Image as PILImg
    with PILImg.open(path) as im:
        iw, ih = im.size
    mw = max_w or (CONTENT_W - 0.5*cm)
    scale = min(mw/iw, max_h/ih, 1.0)
    rw, rh = iw*scale, ih*scale
    img = Image(path, width=rw, height=rh)
    img.hAlign = 'CENTER'
    return [spacer(0.3), img, Paragraph(caption, caption_style), spacer(0.2)]

# ── Build story ────────────────────────────────────────────────────────────────
story = []

# ── Cover / Title Block ───────────────────────────────────────────────────────
story.append(spacer(1.5))
story.append(Paragraph("Complete Anatomy of the Liver", title_style))
story.append(Paragraph("With Clinical Correlates", subtitle_style))
story.append(spacer(0.4))
story.append(HRFlowable(width="80%", thickness=3, color=ACCENT_GOLD, hAlign='CENTER', spaceAfter=10))
story.append(spacer(0.4))
story.append(Paragraph(
    "Sources: Bailey &amp; Love's Short Practice of Surgery 28th ed. | Gray's Anatomy for Students | "
    "Guyton &amp; Hall Textbook of Medical Physiology | Yamada's Textbook of Gastroenterology 7th ed. | "
    "Miller's Anesthesia 10th ed.",
    sources_style))
story.append(spacer(2))

# ── Section 1: Overview ───────────────────────────────────────────────────────
story.extend(section_header("1", "Overview and General Features"))
story.append(body(
    "The liver is the <b>largest solid organ</b> in the body, weighing approximately 1.5 kg "
    "(about 2% of total body weight) in the average adult. It sits in the right upper quadrant "
    "of the abdomen beneath the right hemidiaphragm. It is a metabolically indispensable organ "
    "— anhepatic humans survive only 24–48 hours. Uniquely, the liver is the <b>only solid organ "
    "that regenerates</b>, recovering up to 90–100% of its previous volume following resection."
))
story.append(spacer())

# ── Section 2: Embryology ─────────────────────────────────────────────────────
story.extend(section_header("2", "Embryology"))
story.append(body(
    "The primordial liver first appears at the end of gestational <b>week 3</b> as the "
    "\"hepatic diverticulum\" — an outpouching of the distal foregut (future duodenum) "
    "composed of proliferating endodermal cells (hepatoblast cords). By week 4, these cords "
    "grow cranially into the <b>septum transversum</b>. By week 5, capillary plexuses from the "
    "vitelline veins are enmeshed with the growing epithelial sheets to form the "
    "<b>primitive hepatic sinusoids</b>."
))
story.append(body(
    "The cranial part of the diverticulum becomes the liver; the caudal bud becomes the "
    "<b>gallbladder and cystic duct</b>. The stalk narrows to form the extrahepatic biliary system. "
    "The septum transversum mesoderm forms the <b>falciform, coronary, triangular ligaments</b> "
    "and the <b>Glisson capsule</b>."
))
story.extend(clinical_box(
    "Biliary Atresia",
    "Failure of normal bile duct development during embryogenesis leads to biliary atresia — a "
    "progressive fibroinflammatory destruction of bile ducts presenting with conjugated "
    "hyperbilirubinemia in neonates. It is the most common indication for liver transplantation "
    "in children."
))

# ── Section 3: Ligaments ──────────────────────────────────────────────────────
story.extend(section_header("3", "Ligaments and Peritoneal Reflections"))
story.append(body(
    "The liver is covered by <b>visceral peritoneum (serosa)</b> with an underlying layer of "
    "connective tissue called <b>Glisson's capsule</b>. At the porta hepatis, the capsule "
    "envelops portal tracts carrying branches of the hepatic artery, portal vein, and bile ducts."
))
story.append(spacer(0.2))
story.extend(make_table(
    ["Ligament", "Description", "Clinical Relevance"],
    [
        ["Falciform ligament", "Remnant of the umbilical vein; runs from umbilicus to interlobar fissure", "Contains ligamentum teres; recanalization in portal hypertension → caput medusae"],
        ["Left triangular ligament", "Superior surface of left lobe to diaphragm", "Division mobilises liver from diaphragm for surgery"],
        ["Right triangular ligament", "Right lobe to right hemidiaphragm", "Division allows liver rotation left for right hepatectomy"],
        ["Lesser omentum / hepatoduodenal ligament", "Between stomach and liver; hilar structures in right free edge", "Basis of Pringle maneuver for hemorrhage control"],
        ["Coronary ligament / bare area", "Peritoneal reflections forming the bare area posteriorly", "Direct contact with diaphragm; site of secondary tumor spread"],
    ],
    col_widths=[4*cm, 6*cm, 6.5*cm]
))
story.extend(clinical_box(
    "Pringle Maneuver",
    "The hepatoduodenal ligament contains: portal vein (posterior), hepatic artery (medial), "
    "and common bile duct (lateral). Compressing this between thumb and index finger "
    "(Pringle maneuver) temporarily occludes hepatic inflow, controlling hemorrhage during "
    "liver surgery. Warm ischemia is generally tolerated for up to 60 minutes."
))

# ── Section 4: Gross Anatomy ──────────────────────────────────────────────────
story.extend(section_header("4", "Gross Anatomy: Lobes and Surfaces"))
story.append(sub_header("Traditional (Morphological) Division"))
story.append(body("The liver has <b>four traditional lobes</b> visible on the visceral surface:"))
for item in [
    "<b>Right lobe</b> — the largest",
    "<b>Left lobe</b> — smaller; separated from right by the falciform ligament anteriorly",
    "<b>Caudate lobe (segment I)</b> — posterior surface, between IVC and ligamentum venosum",
    "<b>Quadrate lobe</b> — inferior surface, between the gallbladder and ligamentum teres",
]:
    story.append(bullet(item))
story.append(spacer(0.3))
story.append(sub_header("Surfaces"))
story.extend(make_table(
    ["Surface", "Description"],
    [
        ["Diaphragmatic", "Convex, smooth, covered by peritoneum except at the bare area"],
        ["Visceral", "Irregular; impressions from stomach, duodenum, right kidney, hepatic flexure, gallbladder"],
        ["Posterior", "Bears the groove for the IVC"],
    ],
    col_widths=[5*cm, 11.5*cm]
))

# ── Section 5: Couinaud Segments ──────────────────────────────────────────────
story.extend(section_header("5", "Couinaud's Segmental Anatomy (Functional)"))
story.append(body(
    "The most surgically important classification divides the liver into <b>8 independent "
    "functional segments</b> (Couinaud's nomenclature), each with its own portal pedicle "
    "(portal vein branch + hepatic artery + bile duct) and independent hepatic venous drainage. "
    "The <b>principal plane (Cantlie's line)</b> divides the liver into left and right halves of "
    "approximately equal size — it runs from the gallbladder fossa to the IVC and contains the "
    "<b>middle hepatic vein</b>."
))
story.extend(img_block(
    "couinaud_segments.png",
    "Fig. 1 — Couinaud's Functional Segments (a) in-situ view and (b) ex vivo. "
    "(Source: Bailey & Love's Surgery 28th ed.)",
    max_h=9*cm
))
story.extend(img_block(
    "couinaud_color.png",
    "Fig. 2 — Color-coded Couinaud segments: superior (top) and visceral (bottom) views. "
    "(Source: Gray's Anatomy for Students)",
    max_h=11*cm
))
story.extend(make_table(
    ["Segment", "Name", "Location"],
    [
        ["I", "Caudate lobe", "Posterior, between IVC and ligamentum venosum"],
        ["II", "Lateral superior", "Left lobe, superior"],
        ["III", "Left anterior lateral / Lateral inferior", "Left lobe, inferior"],
        ["IV (IVa/IVb)", "Medial (Quadrate lobe)", "Between falciform ligament and gallbladder fossa"],
        ["V", "Anterior medial inferior", "Right lobe, anterior inferior"],
        ["VI", "Right anterior lateral / Posterior inferior", "Right lobe, posterior inferior"],
        ["VII", "Posterior lateral superior", "Right lobe, posterior superior"],
        ["VIII", "Posterior medial superior", "Right lobe, superior"],
    ],
    col_widths=[2.5*cm, 5.5*cm, 8.5*cm]
))
story.extend(clinical_box(
    "Hepatic Resection Surgery",
    "Because each Couinaud segment has an independent blood supply and bile drainage, surgeons "
    "can remove any individual segment or combination without compromising the remnant liver. "
    "A right hepatectomy removes segments V, VI, VII, and VIII, leaving I, II, III, and IV. "
    "A left hepatectomy removes II, III, and IV. This segmental precision enables curative "
    "resection of hepatic metastases (e.g., colorectal cancer) and is the basis of living-donor "
    "liver transplantation."
))

# ── Section 6: Blood Supply ───────────────────────────────────────────────────
story.extend(section_header("6", "Blood Supply — Dual Hepatic Circulation"))
story.append(body(
    "The liver receives approximately <b>1350 mL/min</b> of blood (27% of resting cardiac output) "
    "via a dual supply:"
))
story.extend(make_table(
    ["Supply", "Source", "Volume", "Character"],
    [
        ["Portal vein (80%)", "Venous drainage of GI tract + spleen", "~1050 mL/min", "Nutrient-rich, partially deoxygenated"],
        ["Hepatic artery (20%)", "Coeliac trunk → proper hepatic artery", "~300 mL/min", "Fully oxygenated"],
    ],
    col_widths=[3.5*cm, 5.5*cm, 3.5*cm, 4*cm]
))
story.append(sub_header("Portal Vein"))
story.append(body(
    "Formed by the confluence of the <b>splenic vein</b> and <b>superior mesenteric vein</b> "
    "behind the neck of the pancreas. Portal pressure normally ~9 mmHg; hepatic vein pressure ~0 mmHg. "
    "The left branch incorporates the <b>ligamentum venosum</b> (remnant of ductus venosus)."
))
story.extend(img_block(
    "portal_vein.png",
    "Fig. 3 — Intrahepatic branches of the portal vein showing right and left portal veins "
    "and their segmental distribution. (Source: Yamada's Gastroenterology 7th ed.)",
    max_h=8*cm
))
story.append(sub_header("Hepatic Artery"))
story.append(body(
    "Arises from the <b>coeliac trunk</b> as the common hepatic artery → gives off the "
    "gastroduodenal artery → becomes the <b>proper hepatic artery</b> → divides into "
    "<b>right and left hepatic arteries</b>."
))
story.append(body("<b>Surgically important arterial variations:</b>"))
for item in [
    "<b>Replaced right hepatic artery</b> arising from the superior mesenteric artery (SMA) — runs posterior to the CBD",
    "<b>Replaced left hepatic artery</b> arising from the left gastric artery — runs in the lesser omentum",
    "These variants occur in ~20–25% of individuals and must be identified before hepatic or biliary surgery",
]:
    story.append(bullet(item))
story.extend(clinical_box(
    "Portal Hypertension",
    "When portal pressure exceeds 10–12 mmHg, blood shunts through portosystemic collaterals. "
    "Key sites: (1) gastro-oesophageal junction — oesophageal varices (risk of life-threatening "
    "haemorrhage); (2) umbilical veins via ligamentum teres — caput medusae; "
    "(3) superior/inferior haemorrhoidal veins — anorectal varices; "
    "(4) retroperitoneal Retzius veins. Causes include cirrhosis, portal vein thrombosis, "
    "and hepatic vein obstruction (Budd-Chiari)."
))

# ── Section 7: Porta Hepatis ──────────────────────────────────────────────────
story.extend(section_header("7", "Porta Hepatis and Hilum"))
story.append(body(
    "The <b>porta hepatis</b> is a pronounced transverse fissure on the visceral surface. "
    "Hilar structures running in the <b>hepatoduodenal ligament</b> (right free edge of lesser omentum) "
    "enter/exit here:"
))
for item in [
    "<b>Common bile duct</b> — anterolateral",
    "<b>Hepatic artery proper</b> — medial (left side)",
    "<b>Portal vein</b> — posterior",
]:
    story.append(bullet(item))
story.append(body(
    "The right and left hepatic ducts emerge at the hilum to form the <b>common hepatic duct</b>, "
    "joined by the <b>cystic duct</b> from the gallbladder to form the <b>common bile duct (CBD)</b>."
))
story.extend(clinical_box(
    "Calot's Triangle / Hepatocystic Triangle",
    "Bounded by the cystic duct, common hepatic duct, and inferior edge of the liver. "
    "The cystic artery (usually from the right hepatic artery) runs within or near this triangle. "
    "Critical structure identification here is mandatory during cholecystectomy — inadvertent "
    "CBD injury is the most feared complication of laparoscopic cholecystectomy, with an "
    "incidence of 0.3–0.5%."
))

# ── Section 8: Venous Drainage ────────────────────────────────────────────────
story.extend(section_header("8", "Venous Drainage"))
story.append(body(
    "The liver drains via <b>three main hepatic veins</b> directly into the <b>IVC</b> "
    "immediately below the diaphragm:"
))
story.extend(make_table(
    ["Hepatic Vein", "Segments Drained", "Clinical Note"],
    [
        ["Right hepatic vein", "V, VI, VII, VIII", "Can be exposed fully outside the liver parenchyma"],
        ["Middle hepatic vein", "IV, V, VIII", "Runs in the principal plane (Cantlie's line)"],
        ["Left hepatic vein", "II, III (and part of IV)", "Joins middle to form a common trunk in ~80%"],
        ["Short caudate veins (multiple)", "Segment I (caudate lobe)", "Drain directly into IVC — spared in Budd-Chiari"],
    ],
    col_widths=[4*cm, 4.5*cm, 8*cm]
))
story.extend(clinical_box(
    "Budd-Chiari Syndrome",
    "Occlusion of hepatic veins (or IVC) causes congestive hepatopathy, acute liver failure, "
    "and massive ascites. The caudate lobe (segment I) is typically spared because it drains "
    "directly into the IVC via multiple short veins — compensatory caudate hypertrophy is a "
    "characteristic CT/MRI finding that helps confirm the diagnosis."
))
story.extend(clinical_box(
    "Cardiac Hepatomegaly",
    "The liver stores ~450 mL blood (~10% of total blood volume). In right heart failure, "
    "raised hepatic venous pressure causes hepatic congestion and tender hepatomegaly. "
    "Chronic congestion leads to centrilobular necrosis and ultimately 'cardiac cirrhosis' "
    "(macroscopic 'nutmeg liver' appearance with alternating red congested and pale necrotic zones)."
))

# ── Section 9: Lymphatics and Nerves ─────────────────────────────────────────
story.extend(section_header("9", "Lymphatic Drainage and Nerve Supply"))
story.append(sub_header("Lymphatics"))
story.append(body(
    "The liver produces <b>25–50% of thoracic duct lymph</b>. Drainage routes:"
))
for item in [
    "Superficial lymphatics → periportal nodes → coeliac nodes → cisterna chyli",
    "Deep lymphatics (from spaces of Disse) → interlobular channels → portal tracts → hilar nodes",
    "Bare area → diaphragmatic nodes → mediastinal nodes",
]:
    story.append(bullet(item))
story.append(sub_header("Innervation"))
story.extend(make_table(
    ["Type", "Origin", "Distribution"],
    [
        ["Sympathetic", "T7–T10 (postganglionic)", "Arteries, bile ducts, hepatocytes, Kupffer cells, stellate cells"],
        ["Parasympathetic", "Vagus nerve (preganglionic)", "Portal tracts, periportal hepatocytes"],
    ],
    col_widths=[3.5*cm, 5*cm, 8*cm]
))
story.extend(clinical_box(
    "Referred Pain from Liver/Biliary Tree",
    "Hepatic capsule stretch (from abscess, hepatomegaly, or acute hepatitis) causes right upper "
    "quadrant pain. Referred pain is felt in the right shoulder (phrenic nerve, C3–C5) and right "
    "subscapular region (T7–T10 dermatomes) — a classic presentation of biliary colic and "
    "subphrenic abscess."
))

# ── Section 10: Microanatomy ──────────────────────────────────────────────────
story.extend(section_header("10", "Microanatomy — The Liver Lobule"))
story.append(body(
    "The liver contains <b>50,000–100,000 lobules</b>, each a cylindrical structure ~2 mm "
    "in diameter and several mm in length."
))
story.append(sub_header("Classical (Hexagonal) Lobule"))
story.append(body(
    "Organized around a <b>central vein</b> (terminal hepatic venule), with six portal tracts "
    "at the periphery. Hepatocyte plates radiate like spokes of a wheel toward the central vein. "
    "Bile canaliculi run parallel to the sinusoids and drain bile <i>opposite</i> to the "
    "direction of blood flow."
))
story.extend(img_block(
    "lobule_structure.png",
    "Fig. 4 — Basic structure of a liver lobule showing hepatocyte plates, sinusoids, "
    "bile canaliculi, Space of Disse, Kupffer cells, and lymphatics. "
    "(Source: Guyton & Hall Medical Physiology)",
    max_h=9*cm
))
story.append(sub_header("Rappaport's Acinus (Functional Unit)"))
story.append(body(
    "The <b>liver acinus</b> is a diamond-shaped area centered on the <b>terminal portal venule "
    "and hepatic arteriole</b> (the portal triad axis), with two central veins at opposing poles. "
    "It is divided into three zones based on oxygen and nutrient delivery:"
))
story.extends = None
story.extend(make_table(
    ["Zone", "Location", "O₂ Tension", "Predominant Metabolism"],
    [
        ["Zone 1 (periportal)", "Closest to portal triad", "High (60–65 mmHg)", "Gluconeogenesis, fatty acid oxidation, urea synthesis, sulfation, GSH synthesis"],
        ["Zone 2 (midzone)", "Intermediate", "Intermediate", "Mixed; intermediate metabolic functions"],
        ["Zone 3 (perivenous/centrilobular)", "Closest to central vein", "Low (30–35 mmHg)", "Glycolysis, glycogen synthesis, lipogenesis, ketogenesis, glucuronidation, CYP450 drug metabolism"],
    ],
    col_widths=[3.5*cm, 3.5*cm, 3*cm, 6.5*cm]
))
story.extend(img_block(
    "acinus_zones.png",
    "Fig. 5 — (A) Hepatic acinus showing zones 1, 2, 3. (B) Sinusoidal ultrastructure with "
    "Space of Disse, stellate cells, Kupffer cells. (C) Hepatocyte metabolic zonation — "
    "periportal (pp) vs perivenous (pv) pathways. (Source: Miller's Anesthesia 10th ed.)",
    max_h=11*cm
))
story.extend(clinical_box(
    "Zone-Specific Liver Injury",
    "Zone 3 (centrilobular) injury — most susceptible to ischemia (lowest O₂) and to toxins "
    "metabolized by CYP450: paracetamol/acetaminophen toxicity (NAPQI via CYP2E1 → "
    "centrilobular necrosis), right heart failure (congestion → centrilobular necrosis). | "
    "Zone 1 (periportal) injury — phosphorus poisoning, eclampsia of pregnancy, Reye syndrome. | "
    "Zone 2 (midzonal) injury — yellow fever (classic midzonal necrosis, Councilman bodies)."
))

# ── Section 11: Cellular Components ──────────────────────────────────────────
story.extend(section_header("11", "Cellular Components"))
story.append(sub_header("Hepatocytes"))
story.append(body(
    "Hepatocytes make up <b>75–80%</b> of liver cell volume. They are polygonal cells, "
    "25–40 μm in diameter, with a single central nucleus. Three distinct plasma membrane domains:"
))
for item in [
    "<b>Sinusoidal (basolateral) surface</b> — microvilli projecting into the space of Disse; active endocytosis and secretion of plasma proteins",
    "<b>Lateral (intercellular) surface</b> — forms bile canaliculi via hemicanaliculi of two adjacent cells, sealed with tight junctions",
    "<b>Canalicular (apical) surface</b> — bile secretion into the bile canaliculus",
]:
    story.append(bullet(item))
story.append(spacer(0.3))
story.append(sub_header("Sinusoidal Non-Parenchymal Cells"))
story.extend(make_table(
    ["Cell Type", "Location", "Key Function"],
    [
        ["Sinusoidal endothelial cells", "Line sinusoids", "Highly fenestrated (pores ~1 μm) — allow free passage of plasma proteins and lipoproteins into Space of Disse"],
        ["Kupffer cells", "Within sinusoidal lumen", "Resident macrophages; phagocytize bacteria, endotoxin, foreign particles; innate hepatic immunity"],
        ["Hepatic stellate cells (Ito cells)", "Space of Disse", "Store vitamin A (80% of body's retinoids); activated → myofibroblasts → fibrosis/cirrhosis"],
        ["Pit cells", "Sinusoidal lumen", "Large granular lymphocytes (hepatic NK cells); antitumor and antiviral immunity"],
    ],
    col_widths=[4*cm, 4*cm, 8.5*cm]
))
story.append(sub_header("Space of Disse (Perisinusoidal Space)"))
story.append(body(
    "The space between the sinusoidal endothelium and hepatocytes. Contains hepatic stellate cells "
    "and sparse collagen fibers. Connects with interlobular lymphatics. Large fenestrations in "
    "the overlying endothelium allow even large plasma proteins (albumin, lipoproteins) to "
    "diffuse freely into this space, making the liver exceptionally efficient at processing "
    "blood-borne substances."
))
story.extend(clinical_box(
    "Hepatic Fibrosis and Cirrhosis",
    "In chronic liver injury (alcohol, viral hepatitis B/C, NAFLD/NASH), activated hepatic "
    "stellate cells transform from vitamin A-storing cells into myofibroblasts, depositing "
    "collagen (predominantly type I and III) in the Space of Disse. Progressive fibrosis "
    "distorts sinusoidal architecture ('capillarization' — loss of fenestrations), increases "
    "portal resistance, and forms regenerative nodules — the hallmarks of cirrhosis. "
    "NAFLD/NASH is now the most common chronic liver disease in industrialized nations, "
    "strongly associated with obesity and type 2 diabetes."
))

# ── Section 12: Biliary System ─────────────────────────────────────────────────
story.extend(section_header("12", "Biliary System"))
story.append(body(
    "Bile flows <b>opposite to blood flow</b> through the sinusoids:"
))
story.append(Paragraph(
    "<b>Hepatocyte bile canaliculi → Canals of Hering (bile ductules) → "
    "Interlobular bile ducts (in portal tracts) → Right &amp; Left hepatic ducts → "
    "Common hepatic duct + Cystic duct → Common bile duct (CBD) → "
    "Ampulla of Vater → Duodenum</b>",
    ParagraphStyle('pathway', fontName='Helvetica', fontSize=9.5, textColor=MED_BLUE,
                   alignment=TA_CENTER, spaceBefore=8, spaceAfter=8,
                   leading=16, borderPad=8,
                   backColor=LIGHT_BLUE, borderColor=MED_BLUE, borderWidth=1)
))
story.append(body(
    "The <b>bile canaliculi</b> are tiny channels (0.5–1.5 μm diameter) formed between adjacent "
    "hepatocytes by hemicanaliculi, sealed by tight junctions (zona occludens). They are entirely "
    "bounded by hepatocyte plasma membranes — not lined by ductal epithelium. At the interface "
    "with the portal tract, bile enters the <b>Canals of Hering</b> (mixed hepatocyte/cholangiocyte "
    "lining), then the interlobular bile ducts (pure cholangiocyte lining)."
))
story.extend(clinical_box(
    "Cholestasis",
    "When bile flow is obstructed (intrahepatic or extrahepatic), bile acids accumulate. "
    "Features: conjugated hyperbilirubinaemia (jaundice), pruritis (bile acid deposition in skin), "
    "pale stools, dark urine, fat-soluble vitamin deficiency (A, D, E, K). "
    "Causes: choledocholithiasis (gallstones in CBD), primary biliary cholangitis (PBC — "
    "autoimmune destruction of small bile ducts), primary sclerosing cholangitis (PSC — "
    "associated with IBD), pancreatic head carcinoma, drug-induced cholestasis."
))

# ── Section 13: Functions ─────────────────────────────────────────────────────
story.extend(section_header("13", "Key Functions of the Liver"))
story.extend(make_table(
    ["Category", "Functions"],
    [
        ["Metabolic", "Glucose homeostasis (glycolysis, gluconeogenesis, glycogenesis/glycogenolysis); lipid metabolism (cholesterol synthesis, lipoprotein assembly, beta-oxidation, ketogenesis); amino acid catabolism; urea cycle"],
        ["Synthetic", "Albumin; clotting factors I, II, V, VII, VIII, IX, X, XI, XIII; complement proteins; angiotensinogen; IGF-1; acute-phase reactants (CRP, fibrinogen, ferritin)"],
        ["Detoxification", "Drug metabolism via CYP450 system; alcohol metabolism (alcohol dehydrogenase, CYP2E1); bilirubin conjugation (glucuronidation); removal of gut endotoxins"],
        ["Storage", "Glycogen; vitamins A, D, E, K, B12; iron (ferritin/hemosiderin); copper"],
        ["Immunological", "Kupffer cells — phagocytose gut-derived bacteria and endotoxin; produces acute-phase proteins; tolerogenic immune responses to gut antigens"],
        ["Endocrine", "Produces IGF-1 (in response to GH), thrombopoietin, 25-hydroxylation of vitamin D"],
    ],
    col_widths=[4*cm, 12.5*cm]
))

# ── Section 14: Clinical Summary Table ────────────────────────────────────────
story.extend(section_header("14", "Clinical Correlates — Summary Table"))
story.extend(make_table(
    ["Anatomical Feature", "Clinical Significance"],
    [
        ["Dual blood supply (portal 80% / hepatic artery 20%)", "Liver relatively resistant to isolated arterial occlusion; portal venous thrombosis is far more dangerous"],
        ["Couinaud segmental anatomy", "Precise anatomical resection possible for primary and metastatic tumors; living-donor transplantation"],
        ["Zone 3 (centrilobular) hepatocytes", "Most vulnerable to ischemic necrosis and CYP450-mediated drug toxicity (paracetamol, alcohol)"],
        ["Falciform ligament / ligamentum teres", "Recanalization in portal hypertension → caput medusae visible on abdominal examination"],
        ["Caudate lobe (segment I) direct IVC drainage", "Spared in Budd-Chiari syndrome; compensatory hypertrophy is a diagnostic imaging feature"],
        ["Hepatocystic triangle (Calot's)", "Critical surgical anatomy during cholecystectomy; inadvertent CBD injury leading complication"],
        ["Hepatoduodenal ligament", "Basis of Pringle maneuver — manual compression controls total hepatic inflow hemorrhage"],
        ["Glisson's capsule", "Capsule distension → RUQ pain + right shoulder referred pain (phrenic nerve C3–C5)"],
        ["Space of Disse + hepatic stellate cells", "Stellate cell activation → collagen deposition → fibrosis → cirrhosis (NAFLD/NASH, alcohol, viral hepatitis)"],
        ["Sinusoidal endothelial fenestrations", "Loss of fenestrations (capillarization of sinusoids) in cirrhosis impairs hepatocyte–blood exchange, worsening liver dysfunction"],
        ["Bile canalicular tight junctions", "Disruption → intrahepatic cholestasis; seen in drug reactions, total parenteral nutrition, viral hepatitis"],
        ["Hepatic veins draining into IVC", "Hepatic venous pressure gradient (HVPG) >10 mmHg predicts risk of variceal bleeding in cirrhosis"],
    ],
    col_widths=[6*cm, 10.5*cm]
))

# ── Footer note ────────────────────────────────────────────────────────────────
story.append(spacer(0.5))
story.append(HRFlowable(width="100%", thickness=1, color=GREY_LINE))
story.append(spacer(0.2))
story.append(Paragraph(
    "Generated by Orris Medical Education AI | Sources: Bailey &amp; Love's Surgery 28th ed., "
    "Gray's Anatomy for Students, Guyton &amp; Hall Medical Physiology, "
    "Yamada's Gastroenterology 7th ed., Miller's Anesthesia 10th ed.",
    ParagraphStyle('footer', fontName='Helvetica', fontSize=8, textColor=colors.grey,
                   alignment=TA_CENTER, leading=11)
))

# ── Page number callback ───────────────────────────────────────────────────────
def add_page_number(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(colors.HexColor("#888888"))
    canvas.drawCentredString(A4[0]/2, 1.2*cm, f"Page {doc.page}")
    canvas.restoreState()

# ── Build PDF ─────────────────────────────────────────────────────────────────
doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number)
print(f"PDF generated: {OUTPUT}")

cd /home/daytona/workspace/liver-anatomy-pdf && python3 generate_pdf.py 2>&1

~/liver-anatomy-pdf/generate_pdf.py

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/liver-anatomy-pdf/generate_pdf.py'

cd /home/daytona/workspace/liver-anatomy-pdf && python3 generate_pdf.py 2>&1

ls -lh /home/daytona/workspace/liver-anatomy-pdf/Liver_Anatomy_Complete.pdf