GASTROENTEROLOGY - Complete Q&A

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,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics
from reportlab.pdfbase.ttfonts import TTFont

OUTPUT = "/tmp/workspace/gastro-pdf/Gastroenterology_QA.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=2*cm,
    leftMargin=2*cm,
    topMargin=2.2*cm,
    bottomMargin=2*cm,
    title="Gastroenterology Q&A - Davidson's Based",
    author="Medical Study Notes"
)

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle(
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    fontSize=22,
    textColor=colors.HexColor('#1a3c5e'),
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    spaceBefore=0,
    alignment=TA_CENTER,
    fontName='Helvetica-Bold'
)

subtitle_style = ParagraphStyle(
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    alignment=TA_CENTER,
    fontName='Helvetica'
)

q_style = ParagraphStyle(
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    parent=styles['Normal'],
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    spaceAfter=4,
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    rightIndent=8,
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    fontName='Helvetica-Bold',
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    borderPad=6
)

h2_style = ParagraphStyle(
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    textColor=colors.HexColor('#1a3c5e'),
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    spaceBefore=8,
    fontName='Helvetica-Bold',
    borderPad=2,
    leftIndent=0
)

body_style = ParagraphStyle(
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    parent=styles['Normal'],
    fontSize=9.5,
    textColor=colors.HexColor('#222222'),
    spaceAfter=3,
    spaceBefore=1,
    leading=14,
    fontName='Helvetica',
    alignment=TA_JUSTIFY
)

bullet_style = ParagraphStyle(
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    spaceAfter=2,
    spaceBefore=0,
    leading=14,
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    bulletIndent=6,
    fontName='Helvetica'
)

bold_bullet_style = ParagraphStyle(
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)

note_style = ParagraphStyle(
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    leftIndent=10,
    fontName='Helvetica-Oblique',
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)

def Q(num, text):
    return Paragraph(f"Q{num}. {text}", q_style)

def H2(text):
    return Paragraph(text, h2_style)

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

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

def BB(label, text):
    return Paragraph(f"• <b>{label}</b> {text}", bullet_style)

def SP(h=4):
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def HR():
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def make_table(headers, rows, col_widths=None):
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    return t

story = []

# ── COVER ──────────────────────────────────────────────────────────────────
story.append(Spacer(1, 1.5*cm))
story.append(Paragraph("GASTROENTEROLOGY", title_style))
story.append(Paragraph("Complete Question & Answer Notes", subtitle_style))
story.append(Paragraph("Based on Davidson's Principles and Practice of Medicine, 23rd Edition", subtitle_style))
story.append(SP(6))
story.append(HRFlowable(width="80%", thickness=2, color=colors.HexColor('#1a3c5e'), spaceAfter=10, spaceBefore=4))
story.append(SP(4))

topics = [
    "1. Complications of Ulcerative Colitis",
    "2. Causes of Upper GI Bleed & Management of Variceal Bleed",
    "3. Irritable Bowel Syndrome",
    "4. Peptic Ulcer Disease",
    "5. Acute Pancreatitis",
    "6. Gastroesophageal Reflux Disease (GERD)",
    "7 & 8. Malabsorption - Causes & Management",
    "9. Ulcerative Colitis",
    "10. Celiac Disease in Adults",
    "11. UC vs Crohn's Disease (Comparison)",
    "12. Tropical Sprue",
    "13. Upper GI Bleed / Hematemesis - Full Management",
    "14. Extraintestinal Manifestations of UC/IBD",
    "15. Chronic Pancreatitis",
    "16. Zollinger-Ellison Syndrome",
    "17. Role of H. pylori in Gastroduodenal Diseases",
    "18. Inflammatory Bowel Disease - Types, Features, Management",
]
toc_data = [[Paragraph(f"<b>Topics Covered</b>", ParagraphStyle('toch', fontName='Helvetica-Bold', fontSize=10, textColor=colors.white))]]
for t in topics:
    toc_data.append([Paragraph(t, ParagraphStyle('toc', fontName='Helvetica', fontSize=9, textColor=colors.HexColor('#222222'), leading=13))])
toc_table = Table(toc_data, colWidths=[15*cm])
toc_table.setStyle(TableStyle([
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    ('BACKGROUND', (0,1), (-1,-1), colors.HexColor('#f0f6fb')),
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    ('BOTTOMPADDING', (0,0), (-1,-1), 4),
]))
story.append(toc_table)
story.append(PageBreak())

# ═══════════════════════════════════════════════════════════════
# Q1
# ═══════════════════════════════════════════════════════════════
story.append(Q(1, "Complications of Ulcerative Colitis"))
story.append(H2("A. LOCAL COMPLICATIONS"))
story.append(BB("Toxic Megacolon:", "Colonic diameter ≥6 cm + ≥3 of: fever (>38.6°C), tachycardia (>120 bpm), leukocytosis, anemia + systemic toxicity. Most feared complication. Manage: IV steroids, broad-spectrum antibiotics, bowel rest, NG + rectal decompression. Urgent colectomy if no improvement in 24–48 hrs."))
story.append(BB("Perforation:", "Free or contained. Presents with peritoneal signs, fever. Requires urgent surgery. Broad-spectrum IV antibiotics + fluid resuscitation."))
story.append(BB("Massive Hemorrhage:", "Uncommon but life-threatening. May require blood transfusion and emergency colectomy."))
story.append(BB("Stricture:", "From fibrosis; may cause obstruction. Must biopsy to exclude malignancy."))
story.append(BB("Colorectal Cancer:", "Risk increases with extent and duration. Pancolitis >8–10 years → colonoscopy surveillance every 1–5 years."))
story.append(BB("Pseudopolyps:", "Inflammatory polyps; not true neoplasms; indicate previous severe disease."))
story.append(SP())
story.append(H2("B. SYSTEMIC / EXTRAINTESTINAL COMPLICATIONS"))
story.append(P("See Q14 for full extraintestinal manifestations (joints, skin, eyes, liver, etc.)"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q2
# ═══════════════════════════════════════════════════════════════
story.append(Q(2, "Causes of Upper GI Bleed + Management of Variceal Bleed"))
story.append(H2("CAUSES OF UPPER GI BLEED (above ligament of Treitz)"))
cause_data = [
    [Paragraph('<b>Cause</b>', body_style), Paragraph('<b>Frequency</b>', body_style)],
    [Paragraph('Peptic ulcer (DU > GU)', body_style), Paragraph('35–50%', body_style)],
    [Paragraph('Gastric erosions / acute gastropathy', body_style), Paragraph('15–20%', body_style)],
    [Paragraph('Esophageal/gastric varices', body_style), Paragraph('10–20%', body_style)],
    [Paragraph('Mallory-Weiss tear', body_style), Paragraph('5–15%', body_style)],
    [Paragraph('Esophagitis / GERD', body_style), Paragraph('5–10%', body_style)],
    [Paragraph('Gastric cancer', body_style), Paragraph('1–2%', body_style)],
    [Paragraph("Dieulafoy's lesion", body_style), Paragraph('<2%', body_style)],
    [Paragraph('Osler-Weber-Rendu syndrome', body_style), Paragraph('Rare', body_style)],
]
story.append(Table(cause_data, colWidths=[11*cm, 4*cm], style=TableStyle([
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    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
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    ('LEFTPADDING', (0,0), (-1,-1), 6),
])))
story.append(SP(6))
story.append(H2("MANAGEMENT OF VARICEAL BLEED"))
steps = [
    ("1. ABC Resuscitation", "IV access (2 large bore), blood products. Target Hb 7–8 g/dL. Avoid overtransfusion (worsens portal hypertension)."),
    ("2. Correct Coagulopathy", "FFP, Vitamin K, platelets as needed."),
    ("3. Pharmacotherapy (start BEFORE endoscopy)", "Terlipressin (1st choice) OR Octreotide/Somatostatin - cause splanchnic vasoconstriction, reduce portal pressure."),
    ("4. Prophylactic Antibiotics", "Ceftriaxone IV or Ciprofloxacin - reduce bacterial translocation, SBP risk, and rebleeding."),
    ("5. Endoscopy (within 12 hours)", "Endoscopic Variceal Ligation (EVL) - gold standard. Better than sclerotherapy."),
    ("6. Balloon Tamponade", "Sengstaken-Blakemore tube - temporary bridge if endoscopy fails/unavailable. Max 24 hrs."),
    ("7. TIPS", "Transjugular Intrahepatic Portosystemic Shunt - rescue therapy if endoscopy fails."),
    ("8. Secondary Prophylaxis", "Non-selective beta-blockers (propranolol/carvedilol) + EVL sessions."),
]
for step, desc in steps:
    story.append(B(f"<b>{step}:</b> {desc}"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q3
# ═══════════════════════════════════════════════════════════════
story.append(Q(3, "Irritable Bowel Syndrome (IBS)"))
story.append(H2("DEFINITION"))
story.append(P("Functional GI disorder - chronic abdominal pain + altered bowel habits WITHOUT structural or biochemical abnormality."))
story.append(H2("ROME IV DIAGNOSTIC CRITERIA"))
story.append(P("Recurrent abdominal pain ≥1 day/week for ≥3 months, associated with ≥2 of:"))
story.append(B("Related to defecation"))
story.append(B("Change in stool frequency"))
story.append(B("Change in stool form/appearance"))
story.append(H2("SUBTYPES"))
story.append(P("IBS-C (constipation predominant) | IBS-D (diarrhea predominant) | IBS-M (mixed) | IBS-U (unclassified)"))
story.append(H2("CLINICAL FEATURES"))
story.append(B("Abdominal pain/cramps - typically left iliac fossa, relieved by defecation"))
story.append(B("Bloating and distension"))
story.append(B("Alternating bowel habits; mucus in stool (NO blood)"))
story.append(B("Symptoms worsened by stress and meals; NEVER wake patient at night"))
story.append(H2("MANAGEMENT"))
story.append(BB("Lifestyle:", "Low FODMAP diet; soluble fiber supplementation; regular exercise; stress reduction"))
story.append(BB("Antispasmodics:", "Mebeverine, Hyoscine (abdominal cramps)"))
story.append(BB("IBS-C:", "Osmotic laxatives (lactulose, PEG); Linaclotide; Prucalopride"))
story.append(BB("IBS-D:", "Loperamide; Cholestyramine (bile salt malabsorption); Rifaximin"))
story.append(BB("Antidepressants:", "Low-dose TCAs (amitriptyline) for pain modulation; SSRIs for IBS-D predominant"))
story.append(BB("Psychological:", "CBT, hypnotherapy"))
story.append(H2("ALARM FEATURES (EXCLUDE IBS)"))
story.append(P("Blood in stool, nocturnal diarrhea, fever, weight loss, new onset >45 years, family history of CRC/IBD/celiac"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q4
# ═══════════════════════════════════════════════════════════════
story.append(Q(4, "Peptic Ulcer Disease (PUD)"))
story.append(H2("PATHOGENESIS"))
story.append(P("Imbalance between AGGRESSIVE factors (acid, pepsin, H. pylori, NSAIDs, bile) and DEFENSIVE factors (mucus layer, bicarbonate, prostaglandins, mucosal blood flow)."))
story.append(BB("H. pylori:", "Disrupts mucus, produces urease (ammonia). Present in 90% of DU and 70% of GU."))
story.append(BB("NSAIDs:", "Inhibit COX-1 → reduce prostaglandins → reduce mucus/bicarbonate protection."))
story.append(H2("CLINICAL FEATURES"))
story.append(make_table(
    [Paragraph('<b>Feature</b>', body_style), Paragraph('<b>Duodenal Ulcer (DU)</b>', body_style), Paragraph('<b>Gastric Ulcer (GU)</b>', body_style)],
    [
        [Paragraph('Site', body_style), Paragraph('1st part duodenum', body_style), Paragraph('Lesser curvature', body_style)],
        [Paragraph('Pain timing', body_style), Paragraph('2–3 hrs after meals; nocturnal; relieved by food/antacids', body_style), Paragraph('Aggravated by food', body_style)],
        [Paragraph('H. pylori', body_style), Paragraph('90–95%', body_style), Paragraph('70–75%', body_style)],
        [Paragraph('Malignancy risk', body_style), Paragraph('Very low', body_style), Paragraph('Must biopsy to exclude', body_style)],
        [Paragraph('Associated', body_style), Paragraph('Blood group O, hyperacidity', body_style), Paragraph('NSAIDs, anorexia, weight loss', body_style)],
    ],
    col_widths=[4*cm, 5.5*cm, 5.5*cm]
))
story.append(H2("COMPLICATIONS"))
story.append(B("<b>Hemorrhage</b> (most common) - hematemesis / melena"))
story.append(B("<b>Perforation</b> - sudden severe epigastric pain, peritonitis, pneumoperitoneum on erect CXR"))
story.append(B("<b>Pyloric stenosis / Gastric outlet obstruction</b> - succussion splash, projectile vomiting"))
story.append(B("<b>Penetration</b> into adjacent organs (pancreas)"))
story.append(B("<b>Malignant change</b> - GU only (rare)"))
story.append(H2("INVESTIGATIONS"))
story.append(B("H. pylori: Urea breath test (gold standard, non-invasive); Stool antigen; CLO test (biopsy); Serology"))
story.append(B("OGD (endoscopy) with biopsy - mandatory for GU; for diagnosis and assessment"))
story.append(H2("MANAGEMENT"))
story.append(BB("H. pylori eradication (Triple therapy):", "PPI + Clarithromycin + Amoxicillin x 7–14 days. If resistant: Quadruple therapy (PPI + Bismuth + Metronidazole + Tetracycline)"))
story.append(BB("Acid suppression:", "PPI (omeprazole/pantoprazole) - first line. H2 blockers (famotidine) - second line."))
story.append(BB("Stop NSAIDs/aspirin:", "If must continue, co-prescribe PPI."))
story.append(BB("Surgery (rarely needed):", "Highly selective vagotomy, antrectomy"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q5
# ═══════════════════════════════════════════════════════════════
story.append(Q(5, "Acute Pancreatitis"))
story.append(H2("CAUSES (Mnemonic: I GET SMASHED)"))
smashed = [
    ("I", "Idiopathic (10–15%)"),
    ("G", "Gallstones (most common in UK/India ~50%)"),
    ("E", "Ethanol/Alcohol (~35% in developing world)"),
    ("T", "Trauma"),
    ("S", "Steroids"),
    ("M", "Mumps / viruses (Coxsackie B, EBV)"),
    ("A", "Autoimmune (IgG4-related)"),
    ("S", "Scorpion sting (Caribbean)"),
    ("H", "Hyperlipidemia (TG >1000 mg/dL), Hypercalcemia, Hypothermia"),
    ("E", "ERCP (post-procedure)"),
    ("D", "Drugs (azathioprine, valproate, furosemide, tetracycline, L-asparaginase)"),
]
for letter, meaning in smashed:
    story.append(Paragraph(f"• <b>{letter}</b> - {meaning}", bullet_style))

story.append(H2("CLINICAL FEATURES"))
story.append(B("Severe epigastric pain radiating to back ('boring'); relieved by sitting forward"))
story.append(B("Nausea, vomiting, fever, tachycardia"))
story.append(B("Abdominal tenderness, guarding, paralytic ileus"))
story.append(B("<b>Grey Turner's sign</b> - flank ecchymosis (hemorrhagic pancreatitis)"))
story.append(B("<b>Cullen's sign</b> - periumbilical ecchymosis"))

story.append(H2("INVESTIGATIONS"))
story.append(B("Serum amylase (>3x normal; rises 6–12 hrs) OR Serum lipase (more sensitive, stays elevated longer)"))
story.append(B("FBC, LFTs, RFT, Calcium, Glucose, ABG"))
story.append(B("CECT abdomen - gold standard for severity; best at 48–72 hrs (Modified CT Severity Index - MCTSI)"))
story.append(B("Ultrasound - to detect gallstones"))

story.append(H2("SEVERITY: RANSON'S CRITERIA (12 parameters)"))
story.append(P("<b>At Admission:</b> Age >55, WBC >16,000, Glucose >200 mg/dL, LDH >350 IU/L, AST >250 IU/L"))
story.append(P("<b>At 48 hours:</b> Hematocrit fall >10%, BUN rise >5 mg/dL, Ca <8 mg/dL, PaO2 <60 mmHg, Base deficit >4 mEq/L, Fluid sequestration >6L"))
story.append(P("Score ≥3 = severe pancreatitis. Also use BISAP score and APACHE II."))

story.append(H2("COMPLICATIONS"))
story.append(BB("Local:", "Pancreatic necrosis (infected = surgery), Pseudocyst (most common), Abscess, Walled-off necrosis"))
story.append(BB("Systemic:", "ARDS, AKI, DIC, Sepsis, Multiorgan failure, Hypocalcemia, Hyperglycemia"))

story.append(H2("MANAGEMENT"))
story.append(B("<b>Aggressive IV fluid resuscitation</b> - Lactated Ringer's preferred"))
story.append(B("<b>Analgesia</b> - Pethidine (morphine relatively contraindicated - Oddi's sphincter spasm)"))
story.append(B("<b>Nil by mouth</b> → early nasojejunal feeding preferred over TPN"))
story.append(B("<b>Antibiotics</b> - only if infected necrosis (imipenem or meropenem)"))
story.append(B("<b>ERCP + sphincterotomy</b> - gallstone pancreatitis with cholangitis within 24–72 hrs"))
story.append(B("<b>Surgery</b> - necrosectomy for infected necrosis; cholecystectomy after recovery"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q6
# ═══════════════════════════════════════════════════════════════
story.append(Q(6, "Gastroesophageal Reflux Disease (GERD)"))
story.append(H2("PATHOPHYSIOLOGY"))
story.append(B("Transient LES relaxations (TLESRs) - main mechanism of acid reflux"))
story.append(B("Hiatus hernia - predisposes; weak LES; impaired esophageal clearance; delayed gastric emptying"))

story.append(H2("CLINICAL FEATURES"))
story.append(BB("Typical:", "Heartburn (pyrosis), acid regurgitation, waterbrash - worse postprandially and on bending/lying"))
story.append(BB("Atypical:", "Chronic cough, hoarseness, asthma, laryngitis, non-cardiac chest pain, globus"))

story.append(H2("COMPLICATIONS"))
story.append(B("Erosive esophagitis"))
story.append(B("Peptic stricture (dysphagia to solids)"))
story.append(B("<b>Barrett's esophagus</b> - squamous → columnar metaplasia (intestinal); premalignant → risk of adenocarcinoma"))
story.append(B("Esophageal adenocarcinoma"))

story.append(H2("INVESTIGATIONS"))
story.append(B("24-hour pH monitoring - gold standard for diagnosis"))
story.append(B("OGD (endoscopy) - for complications, alarm symptoms; Los Angeles Classification of esophagitis"))
story.append(B("Esophageal manometry - assess LES pressure and peristalsis"))

story.append(H2("MANAGEMENT"))
story.append(BB("Lifestyle:", "Weight loss, elevate head of bed, avoid large meals, coffee, alcohol, smoking"))
story.append(BB("PPI (1st line):", "Omeprazole/Pantoprazole - most effective acid suppression"))
story.append(BB("H2 blockers (2nd line):", "Famotidine"))
story.append(BB("Antacids/Alginates:", "Gaviscon - PRN symptom relief"))
story.append(BB("Prokinetics:", "Metoclopramide - adjunct"))
story.append(BB("Surgery:", "Laparoscopic Nissen fundoplication - refractory cases or hiatus hernia"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q7 & Q8
# ═══════════════════════════════════════════════════════════════
story.append(Q("7 & 8", "Malabsorption - Causes, Investigations & Management"))
story.append(H2("CAUSES"))
story.append(make_table(
    [Paragraph('<b>Category</b>', body_style), Paragraph('<b>Examples</b>', body_style)],
    [
        [Paragraph('Intraluminal (digestion defect)', body_style), Paragraph('Pancreatic insufficiency (chronic pancreatitis, CF); Bile salt deficiency (cholestasis, ileal resection, bacterial overgrowth)', body_style)],
        [Paragraph('Mucosal (absorption defect)', body_style), Paragraph("Celiac disease, Tropical sprue, Whipple's disease, Crohn's disease, Radiation enteritis, Short bowel syndrome", body_style)],
        [Paragraph('Post-mucosal (lymphatic obstruction)', body_style), Paragraph('Intestinal lymphangiectasia, Lymphoma', body_style)],
    ],
    col_widths=[5.5*cm, 9.5*cm]
))
story.append(H2("CLINICAL FEATURES"))
story.append(BB("Fat malabsorption (steatorrhea):", "Pale, bulky, oily, offensive stools; float in toilet; weight loss"))
story.append(BB("Protein:", "Edema, muscle wasting"))
story.append(BB("Carbohydrate:", "Bloating, flatulence, osmotic diarrhea"))
story.append(BB("Iron deficiency:", "Anemia, glossitis, koilonychia"))
story.append(BB("Folate/B12:", "Megaloblastic anemia; B12 in terminal ileal disease → SACD"))
story.append(BB("Fat-soluble vitamins:", "A: night blindness; D: osteomalacia, tetany; K: bleeding; E: neuropathy"))

story.append(H2("INVESTIGATIONS"))
story.append(B("Sudan stain / Fecal fat >6 g/day - confirms steatorrhea"))
story.append(B("D-Xylose test - mucosal disease (abnormal in small bowel disease; normal in pancreatic insufficiency)"))
story.append(B("Fecal elastase - low in pancreatic exocrine insufficiency"))
story.append(B("Small bowel biopsy (endoscopic) - gold standard for mucosal disease"))
story.append(B("Hydrogen breath test - bacterial overgrowth / lactose intolerance"))
story.append(B("Anti-tTG IgA, Anti-EMA - celiac disease serology"))

story.append(H2("MANAGEMENT"))
story.append(B("Treat underlying cause (gluten-free diet for celiac, PERT for pancreatic insufficiency, antibiotics for SIBO)"))
story.append(B("Nutritional supplementation: fat-soluble vitamins (A, D, E, K), iron, B12/folate, calcium"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q9
# ═══════════════════════════════════════════════════════════════
story.append(Q(9, "Ulcerative Colitis (UC)"))
story.append(H2("DEFINITION & PATHOLOGY"))
story.append(P("Chronic relapsing IBD affecting colorectal mucosa. Always starts at rectum and extends proximally (continuous lesions). Inflammation limited to mucosa and submucosa. Crypt abscesses, goblet cell depletion."))

story.append(H2("CLINICAL FEATURES"))
story.append(B("<b>Bloody diarrhea with mucus</b> - hallmark symptom"))
story.append(B("Tenesmus, urgency, crampy abdominal pain"))
story.append(B("Proctitis: constipation + rectal bleeding (only rectum involved)"))
story.append(B("Fever, weight loss, fatigue in severe disease"))

story.append(H2("TRUELOVE & WITTS SEVERITY (exam favorite)"))
story.append(make_table(
    [Paragraph('<b>Feature</b>', body_style), Paragraph('<b>Mild</b>', body_style), Paragraph('<b>Moderate</b>', body_style), Paragraph('<b>Severe</b>', body_style)],
    [
        [Paragraph('Motions/day', body_style), Paragraph('<4', body_style), Paragraph('4–6', body_style), Paragraph('>6', body_style)],
        [Paragraph('Blood in stool', body_style), Paragraph('Small', body_style), Paragraph('Moderate', body_style), Paragraph('Large', body_style)],
        [Paragraph('Temp (°C)', body_style), Paragraph('Normal', body_style), Paragraph('Intermediate', body_style), Paragraph('>37.8', body_style)],
        [Paragraph('Pulse (bpm)', body_style), Paragraph('Normal', body_style), Paragraph('Intermediate', body_style), Paragraph('>90', body_style)],
        [Paragraph('Hemoglobin', body_style), Paragraph('Normal', body_style), Paragraph('Intermediate', body_style), Paragraph('<10.5 g/dL', body_style)],
        [Paragraph('ESR (mm/hr)', body_style), Paragraph('<20', body_style), Paragraph('Intermediate', body_style), Paragraph('>30', body_style)],
    ],
    col_widths=[4.5*cm, 3.5*cm, 3.5*cm, 3.5*cm]
))

story.append(H2("INVESTIGATIONS"))
story.append(B("Flexible sigmoidoscopy/colonoscopy + biopsy (NOT full colonoscopy in acute severe UC)"))
story.append(B("Stool cultures (exclude infective colitis)"))
story.append(B("Blood: FBC, CRP, ESR, albumin; AXR to exclude toxic megacolon"))
story.append(B("pANCA positive (70%), ASCA negative"))

story.append(H2("MANAGEMENT"))
story.append(BB("Mild-Moderate:", "5-ASA compounds (mesalazine) topical ± oral; steroids for flares"))
story.append(BB("Severe (admit):", "IV Hydrocortisone; if no response 72 hrs → Rescue: IV Ciclosporin or Infliximab; fail → colectomy"))
story.append(BB("Maintenance:", "Mesalazine; Azathioprine (steroid-sparing); Biologics (infliximab, vedolizumab)"))
story.append(BB("Surgery (CURATIVE):", "Proctocolectomy + ileoanal pouch (IPAA); indications: failed medical therapy, dysplasia/cancer, toxic megacolon/perforation"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q10
# ═══════════════════════════════════════════════════════════════
story.append(Q(10, "Celiac Disease in Adults"))
story.append(H2("DEFINITION"))
story.append(P("Immune-mediated enteropathy triggered by gluten (gliadin fraction) in genetically susceptible individuals. HLA-DQ2 (90%), HLA-DQ8 (10%)."))

story.append(H2("PATHOLOGY (Marsh Classification)"))
story.append(P("Villous atrophy + crypt hyperplasia + increased intraepithelial lymphocytes (IELs). Marsh I-IIIc scale."))

story.append(H2("CLINICAL FEATURES"))
story.append(BB("Classic (malabsorptive):", "Diarrhea, steatorrhea, weight loss, bloating (more common in children)"))
story.append(BB("Non-classical (common in adults):", "Iron deficiency anemia (MOST COMMON presentation in adults), osteoporosis, peripheral neuropathy, ataxia, infertility, elevated transaminases, short stature"))
story.append(BB("Dermatitis herpetiformis:", "Intensely itchy vesicular rash on elbows, knees, buttocks - PATHOGNOMONIC association with celiac"))

story.append(H2("INVESTIGATIONS"))
story.append(B("<b>Anti-tissue transglutaminase IgA (anti-tTG IgA)</b> - best initial test (sensitivity 95%)"))
story.append(B("<b>Anti-endomysial antibody IgA (AEmA)</b> - highly specific"))
story.append(B("<b>Total serum IgA</b> - check first (IgA deficiency in 2-3% gives false negative → use IgG-based tests)"))
story.append(B("<b>Duodenal/jejunal biopsy (endoscopy)</b> - gold standard (multiple biopsies from 2nd/3rd part duodenum)"))
story.append(P("<b>Key rule:</b> Tests MUST be done while patient is on a GLUTEN-CONTAINING diet."))

story.append(H2("MANAGEMENT"))
story.append(B("<b>Lifelong strict gluten-free diet (GFD)</b> - avoid wheat, barley, rye"))
story.append(B("Nutritional supplements: Iron, folate, B12, Vitamin D, calcium"))
story.append(B("Monitor with anti-tTG titers (should fall on GFD) + DEXA scan for osteoporosis"))
story.append(B("Refractory celiac: Immunosuppressants; risk of EATL (enteropathy-associated T-cell lymphoma)"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q11
# ═══════════════════════════════════════════════════════════════
story.append(Q(11, "Ulcerative Colitis vs Crohn's Disease"))
uc_cd_data = [
    [Paragraph('<b>Feature</b>', body_style), Paragraph('<b>Ulcerative Colitis</b>', body_style), Paragraph('<b>Crohn\'s Disease</b>', body_style)],
    [Paragraph('Location', body_style), Paragraph('Rectum to colon (colorectal ONLY)', body_style), Paragraph('Any part of GI tract (mouth to anus)', body_style)],
    [Paragraph('Distribution', body_style), Paragraph('Continuous', body_style), Paragraph('Skip lesions (discontinuous)', body_style)],
    [Paragraph('Rectal involvement', body_style), Paragraph('ALWAYS (100%)', body_style), Paragraph('Spared in ~50%', body_style)],
    [Paragraph('Depth of inflammation', body_style), Paragraph('Mucosa only', body_style), Paragraph('Transmural (full thickness)', body_style)],
    [Paragraph('Macroscopic', body_style), Paragraph('Erythema, granularity, pseudopolyps', body_style), Paragraph('Cobblestone, linear ulcers, strictures', body_style)],
    [Paragraph('Fistulae', body_style), Paragraph('Rare', body_style), Paragraph('Common (perianal, enteroenteric)', body_style)],
    [Paragraph('Perianal disease', body_style), Paragraph('Rare', body_style), Paragraph('Common (fissures, fistulae, abscess)', body_style)],
    [Paragraph('Granulomas', body_style), Paragraph('ABSENT', body_style), Paragraph('Present (non-caseating) ~50%', body_style)],
    [Paragraph('Bleeding', body_style), Paragraph('Common, prominent', body_style), Paragraph('Less common', body_style)],
    [Paragraph('Malabsorption/B12', body_style), Paragraph('Not typical', body_style), Paragraph('Yes (terminal ileum)', body_style)],
    [Paragraph('Smoking', body_style), Paragraph('PROTECTIVE', body_style), Paragraph('RISK FACTOR', body_style)],
    [Paragraph('Serology', body_style), Paragraph('pANCA+ (70%)', body_style), Paragraph('ASCA+ (60%)', body_style)],
    [Paragraph('Surgery', body_style), Paragraph('CURATIVE (colectomy)', body_style), Paragraph('NOT curative (recurrence)', body_style)],
    [Paragraph('Cancer risk', body_style), Paragraph('Higher (CRC)', body_style), Paragraph('Lower (but present)', body_style)],
]
t = Table(uc_cd_data, colWidths=[4.5*cm, 5.25*cm, 5.25*cm])
t.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a3c5e')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTNAME', (0,1), (-1,-1), 'Helvetica'),
    ('FONTSIZE', (0,0), (-1,-1), 8.5),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.white, colors.HexColor('#eaf1f8')]),
    ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#aaaaaa')),
    ('TOPPADDING', (0,0), (-1,-1), 3), ('BOTTOMPADDING', (0,0), (-1,-1), 3),
    ('LEFTPADDING', (0,0), (-1,-1), 5),
    ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
]))
story.append(t)
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q12
# ═══════════════════════════════════════════════════════════════
story.append(Q(12, "Tropical Sprue"))
story.append(H2("DEFINITION"))
story.append(P("Acquired malabsorption syndrome affecting residents/visitors of tropical regions (Indian subcontinent, SE Asia, Caribbean); responds to tetracycline."))

story.append(H2("ETIOLOGY"))
story.append(P("Possibly infectious (E. coli, Klebsiella, Enterobacter). Affects small bowel mucosa including terminal ileum (unlike celiac which spares ileum)."))

story.append(H2("CLINICAL FEATURES"))
story.append(B("Chronic diarrhea and steatorrhea"))
story.append(B("Abdominal bloating and cramps; weight loss, fatigue"))
story.append(B("<b>Megaloblastic anemia</b> - folate deficiency (early), B12 deficiency (later - ileal involvement)"))
story.append(B("Glossitis, stomatitis, malnutrition, edema"))

story.append(H2("INVESTIGATIONS"))
story.append(B("Elevated fecal fat; megaloblastic anemia; low folate and B12"))
story.append(B("Small bowel biopsy - PARTIAL villous atrophy (vs celiac: subtotal/total)"))
story.append(B("Negative anti-tTG (distinguishes from celiac disease)"))

story.append(H2("MANAGEMENT"))
story.append(B("<b>Tetracycline</b> 250 mg QDS x 3–6 months (cornerstone of treatment)"))
story.append(B("<b>Folic acid</b> supplementation - rapid clinical improvement"))
story.append(B("<b>Vitamin B12</b> if deficient"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q13
# ═══════════════════════════════════════════════════════════════
story.append(Q(13, "Upper GI Bleed / Hematemesis - Clinical Features, Etiology, Diagnosis & Management"))
story.append(H2("CLINICAL PRESENTATION"))
story.append(BB("Hematemesis:", "Vomiting bright red blood OR coffee-ground material (dark, digested blood)"))
story.append(BB("Melena:", "Black, tarry, offensive stool (≥60 mL blood oxidized in GI tract)"))
story.append(BB("Shock:", "Tachycardia, hypotension, pallor, cold extremities, confusion"))

story.append(H2("GLASGOW-BLATCHFORD SCORE (pre-endoscopy risk)"))
story.append(P("Parameters: blood urea, hemoglobin, systolic BP, pulse, melena, syncope, liver disease, cardiac failure. Score 0 = can manage as outpatient."))

story.append(H2("FORREST CLASSIFICATION (endoscopic findings - peptic ulcer)"))
story.append(make_table(
    [Paragraph('<b>Class</b>', body_style), Paragraph('<b>Finding</b>', body_style), Paragraph('<b>Action</b>', body_style)],
    [
        [Paragraph('Ia', body_style), Paragraph('Active spurting', body_style), Paragraph('Treat endoscopically', body_style)],
        [Paragraph('Ib', body_style), Paragraph('Active oozing', body_style), Paragraph('Treat endoscopically', body_style)],
        [Paragraph('IIa', body_style), Paragraph('Non-bleeding visible vessel', body_style), Paragraph('Treat endoscopically', body_style)],
        [Paragraph('IIb', body_style), Paragraph('Adherent clot', body_style), Paragraph('Treat or observe', body_style)],
        [Paragraph('IIc', body_style), Paragraph('Flat pigmented spot', body_style), Paragraph('Observe', body_style)],
        [Paragraph('III', body_style), Paragraph('Clean base', body_style), Paragraph('Discharge possible', body_style)],
    ],
    col_widths=[2.5*cm, 6.5*cm, 6*cm]
))

story.append(H2("MANAGEMENT STEPS"))
story.append(B("<b>Resuscitation:</b> A, B, C; 2 large bore IV lines; crossmatch; fluid replacement"))
story.append(B("<b>Transfuse:</b> Restrictive strategy - target Hb >7–8 g/dL"))
story.append(B("<b>IV PPI infusion:</b> Omeprazole/Pantoprazole (for suspected ulcer bleed)"))
story.append(B("<b>Urgent endoscopy:</b> Within 24 hrs (6–12 hrs if hemodynamically unstable)"))
story.append(B("<b>Endoscopic Rx:</b> Dual therapy - adrenaline injection (1:10,000) + thermal/mechanical (clips, heater probe)"))
story.append(B("<b>Interventional radiology (embolization):</b> If endoscopy fails"))
story.append(B("<b>Surgery:</b> Last resort - oversewing, Billroth gastrectomy"))
story.append(P("For variceal bleed management - see Q2 above."))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q14
# ═══════════════════════════════════════════════════════════════
story.append(Q(14, "Extraintestinal Manifestations (EIM) of UC/IBD"))
story.append(H2("A. PARALLEL DISEASE ACTIVITY (correlate with colitis flare)"))
story.append(B("Peripheral arthropathy - Type 1: pauciarticular, large joints; Type 2: polyarticular, small joints"))
story.append(B("Erythema nodosum - tender red nodules on shins"))
story.append(B("Episcleritis - redness of eye, painless"))
story.append(B("Mouth ulcers (aphthous)"))

story.append(H2("B. INDEPENDENT OF DISEASE ACTIVITY"))
story.append(B("<b>Ankylosing spondylitis</b> - HLA-B27 associated; persistent back pain; sacroiliitis"))
story.append(B("<b>Pyoderma gangrenosum</b> - painful deep ulcers on lower limbs; treat with systemic steroids"))
story.append(B("<b>Uveitis/Iritis</b> - painful red eye; requires urgent ophthalmology"))
story.append(B("<b>Primary Sclerosing Cholangitis (PSC)</b> - MOST COMMONLY associated with UC; onion-skin fibrosis; 'beads on a string' on ERCP/MRCP; risk of cholangiocarcinoma"))

story.append(H2("C. METABOLIC & NUTRITIONAL"))
story.append(B("Osteoporosis (steroids + malabsorption)"))
story.append(B("Iron deficiency and anemia of chronic disease"))
story.append(B("Gallstones - ileal disease → bile salt malabsorption (Crohn's)"))
story.append(B("Renal oxalate stones (Crohn's > UC)"))
story.append(B("Thromboembolic disease - hypercoagulable state; PE, DVT"))
story.append(B("Amyloidosis (secondary, rare)"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q15
# ═══════════════════════════════════════════════════════════════
story.append(Q(15, "Chronic Pancreatitis"))
story.append(H2("DEFINITION"))
story.append(P("Chronic progressive inflammatory disease of the pancreas with irreversible structural damage leading to exocrine and endocrine insufficiency."))

story.append(H2("CAUSES (TIGAR-O Classification)"))
story.append(B("<b>T</b> - Toxic-metabolic: Alcohol (70–80% - #1 cause), smoking, hyperlipidemia, hypercalcemia"))
story.append(B("<b>I</b> - Idiopathic"))
story.append(B("<b>G</b> - Genetic: PRSS1 (hereditary pancreatitis), CFTR, SPINK1 mutations"))
story.append(B("<b>A</b> - Autoimmune: IgG4-related (Type 1 AIP); responds to steroids"))
story.append(B("<b>R</b> - Recurrent/severe acute pancreatitis"))
story.append(B("<b>O</b> - Obstructive: Pancreatic duct stricture, divisum, tumor"))

story.append(H2("CLINICAL FEATURES"))
story.append(B("<b>Pain</b> - chronic epigastric, radiating to back; worsened by meals/alcohol; relieved by sitting forward; may 'burn out' over years"))
story.append(B("<b>Steatorrhea</b> - when >90% exocrine function lost; pale oily stools"))
story.append(B("<b>Diabetes mellitus (Type 3c)</b> - endocrine insufficiency (late feature)"))
story.append(B("Weight loss, malnutrition"))

story.append(H2("INVESTIGATIONS"))
story.append(B("<b>CT abdomen</b> - pancreatic calcification (PATHOGNOMONIC), ductal dilatation, atrophy"))
story.append(B("<b>Fecal elastase</b> - low (best non-invasive test for exocrine insufficiency)"))
story.append(B("MRI/MRCP - ductal anatomy"))
story.append(B("EUS - most sensitive for early disease"))
story.append(B("ERCP - 'chain of lakes' appearance (ductal strictures + dilations) - not first-line"))

story.append(H2("COMPLICATIONS"))
story.append(B("Pseudocyst, bile duct obstruction, duodenal obstruction"))
story.append(B("Splenic vein thrombosis → gastric varices"))
story.append(B("Pancreatic cancer risk - increased x10"))

story.append(H2("MANAGEMENT"))
story.append(B("<b>Stop alcohol and smoking</b> - MOST IMPORTANT step"))
story.append(B("<b>Analgesia:</b> Step-up - paracetamol → NSAIDs → tramadol → opioids → celiac plexus nerve block"))
story.append(B("<b>PERT (Pancreatic Enzyme Replacement Therapy):</b> Creon with every meal + fat-soluble vitamin supplementation"))
story.append(B("<b>Diabetes:</b> Insulin; avoid sulfonylureas (hypoglycemia risk with exocrine insufficiency)"))
story.append(B("<b>Endoscopic:</b> ERCP + stenting for ductal obstruction, stone extraction"))
story.append(B("<b>Surgery:</b> Puestow procedure (dilated duct); Frey's/Beger's; Whipple's (head disease + suspected malignancy)"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q16
# ═══════════════════════════════════════════════════════════════
story.append(Q(16, "Zollinger-Ellison Syndrome (ZES)"))
story.append(H2("DEFINITION"))
story.append(P("Gastrin-secreting tumor (gastrinoma) → hypergastrinemia → gastric acid hypersecretion → multiple, refractory, atypically located peptic ulcers."))

story.append(H2("KEY FACTS"))
story.append(B("<b>Location:</b> 'Gastrinoma triangle' (90%) - duodenum 2nd/3rd parts, pancreatic head, cystic duct-CBD junction"))
story.append(B("25–30% part of <b>MEN-1</b> syndrome (3 P's: Pituitary, Parathyroid, Pancreatic tumors)"))
story.append(B("60–70% of gastrinomas are malignant"))

story.append(H2("CLINICAL FEATURES"))
story.append(B("Multiple, refractory, atypically located ulcers (distal duodenum, jejunum)"))
story.append(B("Severe epigastric pain unresponsive to standard PPI doses"))
story.append(B("<b>Diarrhea and steatorrhea</b> - high acid inactivates pancreatic enzymes, precipitates bile salts"))
story.append(B("Severe GERD/esophagitis; weight loss"))

story.append(H2("INVESTIGATIONS"))
story.append(B("<b>Fasting serum gastrin >1000 pg/mL</b> (normal <100) - highly suggestive (gastric pH must be <2)"))
story.append(B("<b>Secretin stimulation test</b> - if gastrin 100–1000; paradoxical rise >200 pg/mL = positive for ZES"))
story.append(B("<b>Tumor localization:</b> EUS (best), CT/MRI, Somatostatin receptor scintigraphy (Octreotide scan), PET-CT"))
story.append(B("Endoscopy - prominent gastric rugae, multiple ulcers"))

story.append(H2("MANAGEMENT"))
story.append(B("<b>High-dose PPI</b> (omeprazole 60–80 mg/day) - controls acid hypersecretion; mainstay of medical therapy"))
story.append(B("<b>Surgical resection</b> of gastrinoma - if localized and no metastases (aim for cure)"))
story.append(B("<b>Somatostatin analogues</b> (octreotide/lanreotide) - for metastatic disease"))
story.append(B("Chemotherapy for malignant gastrinoma (streptozotocin + 5-FU)"))
story.append(B("<b>Screen for MEN-1</b> in family members"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q17
# ═══════════════════════════════════════════════════════════════
story.append(Q(17, "Role of H. pylori in Gastroduodenal Diseases"))
story.append(H2("KEY FACTS ABOUT H. PYLORI"))
story.append(B("Gram-negative, spiral, microaerophilic bacterium living under gastric mucus layer"))
story.append(B("Urease-producing - converts urea to ammonia, neutralizes acid → bacterial survival"))
story.append(B("Virulence: <b>CagA</b> (cytotoxin-associated gene A) - increased pathogenicity; <b>VacA</b> (vacuolating cytotoxin)"))

story.append(H2("DISEASES CAUSED BY H. PYLORI"))
story.append(BB("1. Chronic active gastritis (Type B):", "Almost all infected individuals"))
story.append(BB("2. Duodenal ulcer:", "90–95% of DU; eradication reduces recurrence from 80% to <5%/yr"))
story.append(BB("3. Gastric ulcer:", "70–75% of GU"))
story.append(BB("4. Gastric adenocarcinoma:", "WHO Group 1 carcinogen; Correa cascade: H. pylori → chronic gastritis → atrophy → intestinal metaplasia → dysplasia → cancer; 6x increased risk"))
story.append(BB("5. MALToma:", "H. pylori drives lymphoid tissue in stomach; eradication leads to regression of low-grade MALToma in 75–80% of cases"))
story.append(BB("6. Non-ulcer dyspepsia:", "Some evidence of role"))

story.append(H2("DIAGNOSIS OF H. PYLORI"))
story.append(make_table(
    [Paragraph('<b>Test</b>', body_style), Paragraph('<b>Sensitivity</b>', body_style), Paragraph('<b>Notes</b>', body_style)],
    [
        [Paragraph('Urea breath test (13C)', body_style), Paragraph('95%', body_style), Paragraph('Non-invasive; gold standard; stop PPI 2 wks before test', body_style)],
        [Paragraph('Stool antigen test', body_style), Paragraph('94%', body_style), Paragraph('Non-invasive; good for post-treatment confirmation', body_style)],
        [Paragraph('CLO test (rapid urease)', body_style), Paragraph('90–95%', body_style), Paragraph('Requires endoscopic biopsy', body_style)],
        [Paragraph('Histology', body_style), Paragraph('90%', body_style), Paragraph('From biopsy; shows organism', body_style)],
        [Paragraph('Serology (IgG)', body_style), Paragraph('85%', body_style), Paragraph('Cannot confirm ACTIVE infection; persists after eradication', body_style)],
        [Paragraph('Culture', body_style), Paragraph('Gold standard for resistance', body_style), Paragraph('Difficult, slow, not routine', body_style)],
    ],
    col_widths=[4*cm, 3.5*cm, 7.5*cm]
))

story.append(H2("ERADICATION TREATMENT"))
story.append(BB("Triple therapy (1st line):", "PPI + Clarithromycin + Amoxicillin x 7–14 days"))
story.append(BB("Quadruple therapy (resistant/failed):", "PPI + Bismuth + Metronidazole + Tetracycline x 10–14 days"))
story.append(BB("Confirm eradication:", "UBT or stool antigen - 4 weeks after antibiotics, 2 weeks after stopping PPI"))
story.append(HR())

# ═══════════════════════════════════════════════════════════════
# Q18
# ═══════════════════════════════════════════════════════════════
story.append(Q(18, "Inflammatory Bowel Disease (IBD) - Types, Clinical Features & Management"))
story.append(H2("OVERVIEW"))
story.append(P("IBD = Crohn's Disease + Ulcerative Colitis (+IBD-Unclassified ~10%). Peak age 15–35 yrs (bimodal - 2nd peak 50–70 yrs). More common in developed countries, urban areas, western diet."))

story.append(H2("PATHOGENESIS"))
story.append(B("Dysregulated immune response to gut microbiome in genetically susceptible individuals"))
story.append(B("NOD2 mutations - Crohn's disease; HLA associations"))
story.append(B("Key cytokines: TNF-alpha, IL-12, IL-23 pathway (Crohn's); IL-13 (UC)"))
story.append(B("Risk factors: Family history (strongest), smoking (Crohn's risk; protective in UC), NSAIDs, antibiotics"))

story.append(H2("CLINICAL FEATURES - CROHN'S DISEASE"))
story.append(B("Right lower quadrant pain (terminal ileitis - mimics appendicitis)"))
story.append(B("Diarrhea (may lack blood if small bowel only); weight loss; malnutrition; growth retardation (children)"))
story.append(B("Perianal disease (fistulae, tags, abscesses) - characteristic"))
story.append(B("Obstructive symptoms (strictures); fistulating disease (skin, bladder, vagina)"))

story.append(H2("CLINICAL FEATURES - UC"))
story.append(B("<b>Bloody diarrhea with mucus</b> - cardinal feature"))
story.append(B("Tenesmus, urgency, abdominal cramps"))
story.append(B("Proctitis: constipation + rectal bleeding"))

story.append(H2("MANAGEMENT PRINCIPLES"))
story.append(H2("Induction of Remission:"))
story.append(B("Mild-Moderate UC: 5-ASA (mesalazine) topical ± oral; steroids for flares"))
story.append(B("Moderate-Severe UC: Systemic prednisolone (40 mg/day); IV hydrocortisone if severe"))
story.append(B("Crohn's: Corticosteroids; Elemental/polymeric enteral nutrition (especially children); Budesonide (ileal/right-sided)"))

story.append(H2("Maintenance of Remission:"))
story.append(B("UC: Mesalazine (5-ASA); Azathioprine/6-Mercaptopurine (steroid-sparing)"))
story.append(B("Crohn's: Azathioprine/6-MP; Methotrexate"))

story.append(H2("Biologics (moderate-severe refractory IBD):"))
story.append(make_table(
    [Paragraph('<b>Drug</b>', body_style), Paragraph('<b>Mechanism</b>', body_style), Paragraph('<b>Use</b>', body_style)],
    [
        [Paragraph('Infliximab, Adalimumab', body_style), Paragraph('Anti-TNF-alpha', body_style), Paragraph('UC + Crohn\'s', body_style)],
        [Paragraph('Vedolizumab', body_style), Paragraph('Anti-integrin (gut-selective)', body_style), Paragraph('UC + Crohn\'s', body_style)],
        [Paragraph('Ustekinumab', body_style), Paragraph('Anti-IL-12/23', body_style), Paragraph("Crohn's + UC", body_style)],
        [Paragraph('Tofacitinib, Upadacitinib', body_style), Paragraph('JAK inhibitor', body_style), Paragraph('UC', body_style)],
    ],
    col_widths=[5*cm, 5*cm, 5*cm]
))

story.append(H2("Surgery:"))
story.append(B("UC: Proctocolectomy + IPAA (ileal pouch-anal anastomosis) = CURATIVE"))
story.append(B("Crohn's: Resection (not curative; recurrence common); stricturoplasty for strictures; perianal: setons + medical"))

story.append(H2("Monitoring:"))
story.append(B("Colonoscopic surveillance for CRC (UC: every 1–5 yrs based on risk)"))
story.append(B("Fecal calprotectin - surrogate marker of mucosal inflammation"))
story.append(B("Blood: FBC, CRP, albumin, B12, folate, ferritin, Vitamin D"))

story.append(SP(10))
story.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a3c5e'), spaceAfter=6))
story.append(Paragraph(
    "Reference: Davidson's Principles & Practice of Medicine, 23rd Ed. | Yamada's Textbook of Gastroenterology, 7th Ed. | Sleisenger & Fordtran's GI & Liver Disease",
    note_style
))

# ── BUILD ──────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created successfully: {OUTPUT}")

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,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY

OUTPUT = "/tmp/workspace/gastro-pdf/Gastroenterology_QA_Harrison22_Davidson23.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=1.8*cm,
    leftMargin=1.8*cm,
    topMargin=2*cm,
    bottomMargin=2*cm,
    title="Gastroenterology Q&A - Harrison 22nd & Davidson's",
    author="Medical Study Notes"
)

# ── COLOUR PALETTE ──────────────────────────────────────────────────────────
NAVY    = colors.HexColor('#1a3c5e')
BLUE2   = colors.HexColor('#2e6da4')
MCQ_BG  = colors.HexColor('#fff3cd')   # amber highlight for MCQ
MCQ_TXT = colors.HexColor('#7d4e00')
KEY_BG  = colors.HexColor('#e8f4ea')   # light green key-point box
KEY_TXT = colors.HexColor('#1a5c2a')
HR_COL  = colors.HexColor('#2e6da4')
LIGHT   = colors.HexColor('#eaf1f8')
WHITE   = colors.white

styles = getSampleStyleSheet()

def style(name, **kw):
    base = kw.pop('parent', styles['Normal'])
    return ParagraphStyle(name, parent=base, **kw)

title_s   = style('TT', fontSize=22, textColor=NAVY, spaceBefore=0, spaceAfter=4,
                  alignment=TA_CENTER, fontName='Helvetica-Bold')
subtitle_s= style('ST', fontSize=10.5, textColor=BLUE2, spaceAfter=3,
                  alignment=TA_CENTER, fontName='Helvetica')
q_s       = style('QS', fontSize=13, textColor=WHITE, spaceBefore=14, spaceAfter=4,
                  leftIndent=8, rightIndent=8, leading=18,
                  fontName='Helvetica-Bold', backColor=NAVY, borderPad=6)
h2_s      = style('H2', fontSize=11, textColor=NAVY, spaceBefore=8, spaceAfter=2,
                  fontName='Helvetica-Bold')
h3_s      = style('H3', fontSize=10, textColor=BLUE2, spaceBefore=5, spaceAfter=2,
                  fontName='Helvetica-Bold')
body_s    = style('BD', fontSize=9.5, textColor=colors.HexColor('#222222'),
                  spaceAfter=3, spaceBefore=1, leading=14,
                  fontName='Helvetica', alignment=TA_JUSTIFY)
bullet_s  = style('BL', fontSize=9.5, textColor=colors.HexColor('#222222'),
                  spaceAfter=2, spaceBefore=0, leading=14,
                  leftIndent=18, bulletIndent=6, fontName='Helvetica')
mcq_s     = style('MQ', fontSize=9.5, textColor=MCQ_TXT,
                  spaceAfter=2, spaceBefore=2, leading=14,
                  leftIndent=10, rightIndent=6, fontName='Helvetica-Bold',
                  backColor=MCQ_BG, borderPad=4)
key_s     = style('KY', fontSize=9.5, textColor=KEY_TXT,
                  spaceAfter=2, spaceBefore=2, leading=14,
                  leftIndent=10, rightIndent=6, fontName='Helvetica-Bold',
                  backColor=KEY_BG, borderPad=4)
ref_s     = style('RF', fontSize=8, textColor=colors.HexColor('#888888'),
                  spaceAfter=2, spaceBefore=0, fontName='Helvetica-Oblique',
                  alignment=TA_CENTER)
note_s    = style('NT', fontSize=8, textColor=colors.HexColor('#555555'),
                  spaceAfter=4, leftIndent=8, fontName='Helvetica-Oblique',
                  alignment=TA_CENTER)

def Q(num, text):       return Paragraph(f"Q{num}. {text}", q_s)
def H2(t):              return Paragraph(t, h2_s)
def H3(t):              return Paragraph(t, h3_s)
def P(t):               return Paragraph(t, body_s)
def B(t):               return Paragraph(f"• {t}", bullet_s)
def BB(lbl, t):         return Paragraph(f"• <b>{lbl}</b> {t}", bullet_s)
def MCQ(t):             return Paragraph(f"⭐ MCQ POINT: {t}", mcq_s)
def KEY(t):             return Paragraph(f"🔑 KEY FACT: {t}", key_s)
def SP(h=4):            return Spacer(1, h)
def HR():               return HRFlowable(width="100%", thickness=0.6,
                                          color=HR_COL, spaceAfter=5, spaceBefore=5)
def REF(h_page, d_page): return Paragraph(
    f"  Harrison's 22e p.{h_page}   |   Davidson's 23e p.{d_page}", ref_s)

def tbl(headers, rows, widths):
    data = [headers] + rows
    t = Table(data, colWidths=widths)
    t.setStyle(TableStyle([
        ('BACKGROUND',   (0,0), (-1,0), NAVY),
        ('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'),
        ('ROWBACKGROUNDS',(0,1),(-1,-1),[WHITE, LIGHT]),
        ('GRID',         (0,0), (-1,-1), 0.4, colors.HexColor('#aaaaaa')),
        ('VALIGN',       (0,0), (-1,-1), 'MIDDLE'),
        ('TOPPADDING',   (0,0), (-1,-1), 3),
        ('BOTTOMPADDING',(0,0), (-1,-1), 3),
        ('LEFTPADDING',  (0,0), (-1,-1), 5),
    ]))
    return t

def bp(h,t): return Paragraph(f"• <b>{h}</b> {t}", bullet_s)

story = []

# ════════════════════════════ COVER ══════════════════════════════
story.append(Spacer(1, 1.2*cm))
story.append(Paragraph("GASTROENTEROLOGY", title_s))
story.append(Paragraph("Complete Q&A — Exam Edition", subtitle_s))
story.append(Paragraph("Harrison's Principles of Internal Medicine 22nd Edition (2025) | Davidson's 23rd Edition", subtitle_s))
story.append(SP(4))
story.append(HRFlowable(width="85%", thickness=2.5, color=NAVY, spaceAfter=8, spaceBefore=4))
story.append(SP(4))
story.append(Paragraph(
    '<b>⭐ = MCQ HIGH-YIELD POINT &nbsp;&nbsp;&nbsp; 🔑 = KEY EXAM FACT</b>',
    style('LE', fontSize=10, textColor=MCQ_TXT, backColor=MCQ_BG, alignment=TA_CENTER,
          borderPad=6, leading=16, fontName='Helvetica-Bold', spaceAfter=8)))
story.append(SP(4))

topics = [
    "Q1.  Complications of Ulcerative Colitis",
    "Q2.  Causes of Upper GI Bleed & Management of Variceal Bleed",
    "Q3.  Irritable Bowel Syndrome (IBS)",
    "Q4.  Peptic Ulcer Disease",
    "Q5.  Acute Pancreatitis",
    "Q6.  Gastroesophageal Reflux Disease (GERD)",
    "Q7 & Q8.  Malabsorption — Causes, Investigations & Management",
    "Q9.  Ulcerative Colitis",
    "Q10. Celiac Disease in Adults",
    "Q11. UC vs Crohn's Disease — Comparison Table",
    "Q12. Tropical Sprue",
    "Q13. Upper GI Bleed / Hematemesis — Full Management",
    "Q14. Extraintestinal Manifestations of IBD/UC",
    "Q15. Chronic Pancreatitis",
    "Q16. Zollinger-Ellison Syndrome",
    "Q17. Role of H. pylori in Gastroduodenal Diseases",
    "Q18. Inflammatory Bowel Disease — Types, Features & Management",
]
toc_rows = [[Paragraph(f"<b>Topics Covered</b>",
                        style('TH', fontName='Helvetica-Bold', fontSize=9.5, textColor=WHITE))]]
for t in topics:
    toc_rows.append([Paragraph(t, style('TC', fontName='Helvetica', fontSize=9, textColor=colors.HexColor('#222'), leading=13))])
toc_t = Table(toc_rows, colWidths=[16*cm])
toc_t.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), NAVY),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [WHITE, LIGHT]),
    ('BOX', (0,0), (-1,-1), 0.8, NAVY),
    ('LEFTPADDING', (0,0), (-1,-1), 10),
    ('TOPPADDING', (0,0), (-1,-1), 4),
    ('BOTTOMPADDING', (0,0), (-1,-1), 4),
]))
story.append(toc_t)
story.append(PageBreak())

# ════════════════════════════ Q1 ══════════════════════════════
story.append(Q(1, "Complications of Ulcerative Colitis"))
story.append(REF("2603", "818"))
story.append(H2("A. LOCAL COMPLICATIONS"))
story.append(MCQ("Toxic megacolon — most feared local complication of UC. Colonic diameter ≥6 cm."))
story.append(MCQ("Colorectal cancer — greatest risk with pancolitis of >10 years duration."))
story.append(BP := bp("Toxic Megacolon:",
    "Colon diameter ≥6 cm + ≥3 of: fever >38.6°C, tachycardia >120 bpm, leukocytosis, anemia + systemic toxicity. "
    "Manage: IV hydrocortisone, broad-spectrum antibiotics, complete bowel rest, NG + rectal decompression, serial AXR every 6–12 h. "
    "Colectomy if no improvement in 24–48 hrs. Harrison's: patients who do not respond should NOT undergo colonoscopy or barium enema."))
story.append(bp("Perforation:", "Can occur without megacolon. Free perforation → acute abdomen, peritonitis, urgent surgery. IV antibiotics + fluid resuscitation."))
story.append(bp("Massive hemorrhage:", "Uncommon. Colectomy may be required."))
story.append(bp("Stricture:", "Must biopsy to exclude malignancy."))
story.append(MCQ("Colorectal cancer: Risk increases with extent + duration. Pancolitis >10 yrs → surveillance colonoscopy every 1–2 yrs."))
story.append(bp("Pseudopolyps:", "Inflammatory, regenerative. Not premalignant. Seen in long-standing disease."))
story.append(H2("B. SYSTEMIC COMPLICATIONS"))
story.append(P("See Q14 for full extraintestinal manifestations."))
story.append(HR())

# ════════════════════════════ Q2 ══════════════════════════════
story.append(Q(2, "Causes of Upper GI Bleed + Management of Variceal Bleed"))
story.append(REF("360", "785"))
story.append(H2("CAUSES OF UGIB"))
story.append(MCQ("Peptic ulcers are the MOST COMMON cause of UGIB — ~50% of hospitalizations (Harrison's 22e, p.360)."))
story.append(tbl(
    [Paragraph('<b>Cause</b>', body_s), Paragraph('<b>Frequency</b>', body_s)],
    [
        [Paragraph('Peptic ulcer disease (DU > GU)', body_s), Paragraph('~50%', body_s)],
        [Paragraph('Gastric erosions / acute gastropathy', body_s), Paragraph('15–20%', body_s)],
        [Paragraph('Esophageal/gastric varices', body_s), Paragraph('10–20%', body_s)],
        [Paragraph('Mallory-Weiss tear', body_s), Paragraph('5–15%', body_s)],
        [Paragraph('Esophagitis / GERD', body_s), Paragraph('5–10%', body_s)],
        [Paragraph("Dieulafoy's lesion, angiodysplasia", body_s), Paragraph('<2%', body_s)],
        [Paragraph('Gastric cancer, portal hypertensive gastropathy', body_s), Paragraph('1–2%', body_s)],
    ],
    [12*cm, 3.7*cm]
))
story.append(H2("MANAGEMENT OF VARICEAL BLEED"))
story.append(MCQ("Terlipressin = drug of choice for variceal bleed; start BEFORE endoscopy."))
story.append(MCQ("EVL (Endoscopic Variceal Ligation) = gold standard endoscopic treatment — better than sclerotherapy."))
story.append(MCQ("Restrictive transfusion strategy (Hb target 7 g/dL) shown to DECREASE rebleeding and death vs Hb 9 g/dL threshold (Harrison's 22e)."))
story.append(bp("Step 1 – Resuscitation:", "2 large-bore IV lines, crossmatch, aggressive volume replacement, supplemental O2, keep Hb >7 g/dL."))
story.append(bp("Step 2 – Correct coagulopathy:", "FFP, Vitamin K, platelets. Avoid overtransfusion (raises portal pressure)."))
story.append(bp("Step 3 – Pharmacotherapy (start BEFORE scope):", "Terlipressin 2 mg IV 4-hourly (1st choice); OR Octreotide/Somatostatin infusion."))
story.append(bp("Step 4 – Antibiotics:", "Ceftriaxone IV or Ciprofloxacin — reduce bacterial SBP and rebleeding."))
story.append(bp("Step 5 – Endoscopy within 12 hrs:", "EVL is gold standard (clips/banding). Sclerotherapy if EVL not available."))
story.append(bp("Step 6 – Balloon tamponade:", "Sengstaken-Blakemore tube as temporary bridge if endoscopy fails. Max 24 hrs."))
story.append(bp("Step 7 – TIPS:", "Transjugular Intrahepatic Portosystemic Shunt — rescue therapy when endoscopy fails."))
story.append(bp("Step 8 – Secondary prophylaxis:", "Non-selective beta-blockers (propranolol/carvedilol) + EVL sessions."))
story.append(HR())

# ════════════════════════════ Q3 ══════════════════════════════
story.append(Q(3, "Irritable Bowel Syndrome (IBS)"))
story.append(REF("2617", "802"))
story.append(H2("DEFINITION"))
story.append(P("Functional GI disorder — chronic abdominal pain + altered bowel habits WITHOUT structural or biochemical pathology. Harrison's 22e: 'no pathognomonic abnormalities have been identified; diagnosis based on positive clinical features and exclusion of organic disease.'"))
story.append(MCQ("Rome IV Criteria (2016): Recurrent abdominal pain ≥1 day/week for ≥3 months + ≥2 of: (1) related to defecation, (2) change in stool frequency, (3) change in stool form."))
story.append(MCQ("IBS NEVER causes nocturnal diarrhea, rectal bleeding, fever, or weight loss — these are ALARM features."))
story.append(H2("SUBTYPES"))
story.append(P("IBS-C | IBS-D | IBS-M (mixed) | IBS-U (unclassified)"))
story.append(H2("PATHOPHYSIOLOGY (Harrison's 22e)"))
story.append(bp("Gut dysbiosis:", "Acts with genetic + environmental factors to alter intestinal permeability → mast cell activation → altered neuronal and smooth-muscle function."))
story.append(bp("Visceral hypersensitivity:", "Lowered threshold for pain from gut distension."))
story.append(bp("Brain-gut axis dysfunction:", "Psychosocial factors, previous GI infection (post-infectious IBS)."))
story.append(H2("CLINICAL FEATURES"))
story.append(bp("Abdominal pain/cramps:", "LIF most common; relieved by defecation; postprandial."))
story.append(bp("Altered bowel habit:", "Diarrhea, constipation, or mixed. Mucus in stool (no blood)."))
story.append(bp("Bloating and distension."))
story.append(bp("Symptoms worsened by stress and meals; small-volume stool; no systemic signs."))
story.append(KEY("IBS symptoms that ARGUE AGAINST the diagnosis: first onset in old age, progressive course, rectal bleeding, significant weight loss, persistent diarrhea after 48-hr fast, nocturnal diarrhea, steatorrhea. (Harrison's 22e)"))
story.append(H2("MANAGEMENT"))
story.append(bp("Diet:", "Low FODMAP diet; soluble fiber (IBS-C); avoid gas-producing foods."))
story.append(bp("Antispasmodics:", "Mebeverine, Hyoscine butylbromide (for pain)."))
story.append(MCQ("IBS-C: Linaclotide (guanylate cyclase-C agonist) is a newer approved agent."))
story.append(bp("IBS-D:", "Loperamide; Rifaximin (non-absorbable antibiotic); Cholestyramine (bile salt malabsorption)."))
story.append(bp("Antidepressants:", "Low-dose TCAs (amitriptyline) — pain modulation; SSRIs for IBS-D."))
story.append(bp("Psychological:", "CBT, hypnotherapy. Harrison's: psychological therapies shown to be effective."))
story.append(HR())

# ════════════════════════════ Q4 ══════════════════════════════
story.append(Q(4, "Peptic Ulcer Disease (PUD)"))
story.append(REF("2558", "791"))
story.append(H2("DEFINITION (Harrison's 22e)"))
story.append(P("'Disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation.' >90% patients with dyspepsia do NOT have ulcers. Lifetime prevalence ~8.4%. ~15,000 deaths/year in the US from complicated PUD."))
story.append(H2("PATHOGENESIS"))
story.append(MCQ("H. pylori in ~90% of DU and ~70% of GU — most important pathogenic factor."))
story.append(MCQ("NSAIDs: Inhibit COX-1 → reduce prostaglandins → impair mucus/bicarbonate barrier."))
story.append(bp("Parietal cell:", "Secretes HCl via H+/K+-ATPase (proton pump). G-cells (antrum) secrete gastrin → stimulates parietal cells."))
story.append(bp("Aggressive factors:", "Acid, pepsin, H. pylori (urease → ammonia), NSAIDs, bile acids, smoking."))
story.append(bp("Defensive factors:", "Mucus layer, bicarbonate, prostaglandins, mucosal blood flow, surface epithelial renewal."))
story.append(H2("DUODENAL vs GASTRIC ULCER"))
story.append(tbl(
    [Paragraph('<b>Feature</b>', body_s), Paragraph('<b>DU</b>', body_s), Paragraph('<b>GU</b>', body_s)],
    [
        [Paragraph('Site', body_s), Paragraph('1st part of duodenum', body_s), Paragraph('Lesser curvature', body_s)],
        [Paragraph('H. pylori association', body_s), Paragraph('90–95%', body_s), Paragraph('70–75%', body_s)],
        [Paragraph('Pain', body_s), Paragraph('2–3 hrs after meals; nocturnal; RELIEVED by food', body_s), Paragraph('WORSENED by food; anorexia', body_s)],
        [Paragraph('Acid secretion', body_s), Paragraph('Increased', body_s), Paragraph('Normal or decreased', body_s)],
        [Paragraph('Blood group', body_s), Paragraph('Group O', body_s), Paragraph('—', body_s)],
        [Paragraph('Malignancy risk', body_s), Paragraph('Very low', body_s), Paragraph('MUST biopsy to exclude', body_s)],
    ],
    [4*cm, 5.5*cm, 5.5*cm]
))
story.append(H2("COMPLICATIONS"))
story.append(MCQ("Most common complication = Hemorrhage (hematemesis/melena)."))
story.append(MCQ("Perforation: sudden onset severe epigastric pain; erect CXR shows pneumoperitoneum (free air under diaphragm)."))
story.append(bp("Gastric outlet obstruction:", "Pyloric stenosis; succussion splash; projectile vomiting; metabolic alkalosis."))
story.append(bp("Penetration:", "Usually into pancreas (back pain unrelieved by posture change)."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("H. pylori testing: Urea Breath Test (UBT) = gold standard NON-INVASIVE test. Stop PPI 2 wks before."))
story.append(bp("Stool antigen test:", "Good for post-treatment confirmation."))
story.append(bp("CLO test:", "Rapid urease test on biopsy — invasive, done during endoscopy."))
story.append(bp("Serology:", "Cannot confirm active infection — persists after eradication."))
story.append(H2("MANAGEMENT"))
story.append(MCQ("H. pylori eradication reduces recurrence to <10–20% vs 59–67% when organism not eliminated (Harrison's 22e)."))
story.append(bp("Triple therapy (1st line):", "PPI + Clarithromycin + Amoxicillin × 7–14 days."))
story.append(MCQ("Quadruple therapy: PPI + Bismuth + Metronidazole + Tetracycline × 10–14 days — use if clarithromycin resistance or failed 1st line."))
story.append(bp("Acid suppression:", "PPI (omeprazole/pantoprazole) — first line. Harrison's 22e: PPIs superior to H2 blockers for healing."))
story.append(bp("NSAIDs + CVD:", "Harrison's 22e: Patients with CVD on low-dose aspirin who develop GI bleed should NOT discontinue aspirin; restart once bleeding controlled."))
story.append(HR())

# ════════════════════════════ Q5 ══════════════════════════════
story.append(Q(5, "Acute Pancreatitis"))
story.append(REF("2787", "824"))
story.append(H2("GENERAL CONSIDERATIONS (Harrison's 22e)"))
story.append(P("One of the most common principal GI diagnoses in the US — ~300,000 hospitalizations/year. Annual incidence 15–45/100,000. Median hospital stay 4 days. Mortality ~1%. 85–90% cases are SELF-LIMITED and subside within 3–7 days."))
story.append(MCQ("Gallstones + Alcohol account for 80–90% of identified acute pancreatitis cases in the US."))
story.append(MCQ("Gallstones = leading cause in most series (30–60%). Risk of pancreatitis is 4x higher with gallstones <5 mm diameter vs larger stones (Harrison's 22e)."))
story.append(H2("CAUSES (Mnemonic: I GET SMASHED)"))
smashed = [("I","Idiopathic (10–15%)"),("G","Gallstones (30–60% — most common)"),("E","Ethanol/Alcohol (15–30% in USA)"),("T","Trauma"),
           ("S","Steroids"),("M","Mumps/viral: Coxsackie B, CMV, EBV"),("A","Autoimmune — IgG4-related (Type 1 & 2 AIP)"),
           ("S","Scorpion sting"),("H","Hypertriglyceridemia (TG >1000), Hypercalcemia"),
           ("E","ERCP (especially after therapeutic intervention)"),
           ("D","Drugs: azathioprine, 6-MP, sulfonamides, estrogens, tetracycline, valproic acid, DPP-4 inhibitors, 5-ASA")]
for letter, meaning in smashed:
    story.append(Paragraph(f"• <b>{letter}</b> — {meaning}", bullet_s))
story.append(H2("CLINICAL FEATURES"))
story.append(MCQ("Classic: severe epigastric pain radiating to back, 'boring' quality, relieved by sitting forward + leaning forward."))
story.append(bp("Signs:", "Grey Turner's sign (flank ecchymosis), Cullen's sign (periumbilical ecchymosis) — both indicate hemorrhagic pancreatitis."))
story.append(bp("Systemic:", "Fever, tachycardia, hypotension, jaundice (if gallstone-related), paralytic ileus."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("Serum lipase is MORE SENSITIVE and SPECIFIC than amylase and stays elevated longer — preferred diagnostic test."))
story.append(bp("Serum amylase:", "Rises in 6–12 hrs. >3x upper limit of normal. Less specific (also elevated in bowel obstruction, salivary disease)."))
story.append(MCQ("CECT abdomen = gold standard for severity assessment and complications. BEST done at 48–72 hrs."))
story.append(H2("SEVERITY SCORING"))
story.append(MCQ("BISAP Score: B-BUN >25; I-Impaired mental status; S-SIRS (≥2 criteria); A-Age >60; P-Pleural effusion. Score ≥3 = severe."))
story.append(MCQ("SIRS criteria: Temp <36 or >38°C; HR >90; RR >20 or PCO2 <32; WBC >12,000 or <4000. 2 or more = SIRS."))
story.append(bp("Ranson's criteria:", "12 parameters at admission and 48 hrs. Score ≥3 = severe pancreatitis."))
story.append(bp("At Admission:", "Age >55, WBC >16,000, Glucose >200, LDH >350, AST >250."))
story.append(bp("At 48 hrs:", "Hct fall >10%, BUN rise >5, Ca <8, PaO2 <60, Base deficit >4, Fluid sequestration >6 L."))
story.append(H2("COMPLICATIONS"))
story.append(MCQ("Most common local complication = Pancreatic pseudocyst (fluid collection enclosed by fibrous wall)."))
story.append(bp("Local:", "Necrosis (sterile or infected), pseudocyst, abscess, walled-off necrosis, ductal disruption."))
story.append(bp("Systemic:", "ARDS, AKI, DIC, sepsis, multiorgan failure, hypocalcemia, hyperglycemia."))
story.append(H2("MANAGEMENT (Harrison's 22e)"))
story.append(MCQ("Most important intervention = Early, aggressive IV fluid resuscitation. Lactated Ringer's shown to decrease inflammation (lower CRP) vs normal saline."))
story.append(bp("Initial bolus:", "~15–20 mL/kg then 2–3 mL/kg/hr; target urine output >0.5 mL/kg/hr."))
story.append(MCQ("Antibiotics: ONLY if infected necrosis is suspected — carbapenems (imipenem/meropenem). NOT for prophylaxis."))
story.append(bp("Analgesia:", "IV narcotics (pethidine preferred; morphine relatively contraindicated due to Oddi's sphincter spasm)."))
story.append(bp("Nutrition:", "Early enteral (nasojejunal) preferred over TPN. Nil by mouth in acute phase."))
story.append(bp("ERCP + sphincterotomy:", "Gallstone pancreatitis with cholangitis/obstruction — within 24–72 hrs."))
story.append(bp("Surgery:", "Necrosectomy for infected necrosis; cholecystectomy during same admission after recovery."))
story.append(HR())

# ════════════════════════════ Q6 ══════════════════════════════
story.append(Q(6, "Gastroesophageal Reflux Disease (GERD)"))
story.append(REF("2541", "784"))
story.append(H2("PATHOPHYSIOLOGY"))
story.append(MCQ("Main mechanism: Transient Lower Esophageal Sphincter Relaxations (TLESRs) — NOT persistently low LES pressure."))
story.append(bp("Hiatus hernia:", "Predisposes to GERD by impairing the anti-reflux barrier."))
story.append(H2("CLINICAL FEATURES"))
story.append(MCQ("Typical triad: Heartburn (pyrosis) + acid regurgitation + waterbrash — worse postprandially and on lying/bending."))
story.append(bp("Atypical (extra-esophageal):", "Chronic cough, hoarseness, laryngitis, asthma, non-cardiac chest pain, globus."))
story.append(H2("COMPLICATIONS"))
story.append(MCQ("Barrett's esophagus = metaplasia of squamous → columnar (specialized intestinal) epithelium. PREMALIGNANT — risk of esophageal adenocarcinoma."))
story.append(bp("Others:", "Erosive esophagitis (Los Angeles Classification A–D); peptic stricture (dysphagia to solids)."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("24-hour ambulatory pH monitoring = gold standard for diagnosis of GERD."))
story.append(bp("OGD:", "For complications, alarm symptoms, or treatment failure. Biopsy Barrett's for surveillance."))
story.append(bp("Esophageal manometry:", "Assess LES pressure + peristalsis. Needed before fundoplication."))
story.append(H2("MANAGEMENT (Harrison's 22e)"))
story.append(MCQ("Hierarchy of effectiveness: PCABs (potassium competitive acid blockers) > PPIs > H2RAs. Differences most evident with severe esophagitis."))
story.append(MCQ("PPI side effects (Harrison's 22e): Increased risk of C. difficile; impaired B12 and iron absorption; possible slight increased bone fracture risk; interstitial nephritis (rare)."))
story.append(bp("Lifestyle:", "Weight reduction (strongest evidence), elevate HOB, avoid meals 3 hrs before sleep, reduce alcohol/smoking/fatty foods."))
story.append(bp("PPI (1st line):", "Omeprazole/Pantoprazole/Esomeprazole. Dose before meals."))
story.append(bp("Surgery:", "Laparoscopic Nissen fundoplication — controlled trials show similar efficacy to PPI therapy for esophagitis."))
story.append(HR())

# ════════════════════════════ Q7 & Q8 ══════════════════════════════
story.append(Q("7 & 8", "Malabsorption — Causes, Investigations & Management"))
story.append(REF("2731", "818"))
story.append(H2("CAUSES (Three Mechanisms)"))
story.append(tbl(
    [Paragraph('<b>Category</b>', body_s), Paragraph('<b>Examples</b>', body_s)],
    [
        [Paragraph('1. Intraluminal (digestion defect)', body_s),
         Paragraph('Pancreatic insufficiency (chronic pancreatitis, CF, ZES); Bile salt deficiency (cholestasis, ileal resection, SIBO, primary biliary cholangitis)', body_s)],
        [Paragraph('2. Mucosal (absorption defect)', body_s),
         Paragraph("Celiac disease, Tropical sprue, Whipple's disease, Crohn's (terminal ileum), radiation enteritis, short bowel syndrome", body_s)],
        [Paragraph('3. Post-mucosal (lymphatic obstruction)', body_s),
         Paragraph('Intestinal lymphangiectasia, lymphoma, congestive heart failure', body_s)],
    ],
    [5*cm, 11*cm]
))
story.append(H2("CLINICAL FEATURES — NUTRIENT-SPECIFIC"))
story.append(MCQ("Steatorrhea (fat malabsorption) = MOST CLASSIC finding: pale, bulky, oily, offensive stools that float."))
story.append(MCQ("B12 deficiency in malabsorption → most commonly due to TERMINAL ILEAL disease (Crohn's, resection, tropical sprue)."))
story.append(bp("Fat malabsorption:", "Steatorrhea; weight loss; fat-soluble vitamin deficiencies (A, D, E, K)."))
story.append(bp("Vit A:", "Night blindness, Bitot's spots."))
story.append(bp("Vit D:", "Osteomalacia, hypocalcemia, tetany, pathological fractures."))
story.append(bp("Vit K:", "Prolonged PT, bleeding tendency."))
story.append(bp("Iron deficiency:", "Hypochromic microcytic anemia, glossitis, angular cheilosis, koilonychia."))
story.append(bp("Folate/B12:", "Megaloblastic anemia. B12 → also subacute combined degeneration of cord (SACD)."))
story.append(bp("Protein:", "Hypoalbuminemia, pitting edema, muscle wasting."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("D-Xylose test: ABNORMAL in mucosal disease (celiac, tropical sprue); NORMAL in pancreatic insufficiency — distinguishes the two."))
story.append(MCQ("Fecal elastase-1: LOW in pancreatic exocrine insufficiency — best non-invasive pancreatic function test."))
story.append(bp("Stool fat:", "Sudan stain or 72-hr fecal fat collection (>6 g/day = abnormal)."))
story.append(bp("Small bowel biopsy:", "Gold standard for mucosal malabsorption. Villous atrophy in celiac, tropical sprue."))
story.append(bp("Hydrogen breath test:", "SIBO (glucose/lactulose challenge); lactose intolerance."))
story.append(bp("Serology:", "Anti-tTG IgA (celiac screen); serum IgA level (exclude IgA deficiency)."))
story.append(H2("MANAGEMENT"))
story.append(bp("Treat cause:", "GFD (celiac); PERT (pancreatic insufficiency); antibiotics (SIBO); resection avoidance/ostomy reversal (short gut)."))
story.append(bp("Supplementation:", "Fat-soluble vitamins (A, D, E, K), iron, folate, B12, calcium, zinc."))
story.append(HR())

# ════════════════════════════ Q9 ══════════════════════════════
story.append(Q(9, "Ulcerative Colitis (UC)"))
story.append(REF("2599", "807"))
story.append(H2("DEFINITION & PATHOLOGY (Harrison's 22e)"))
story.append(P("UC is a mucosal disease that always involves the rectum and extends proximally in continuity. 40–50% limited to rectum/rectosigmoid; 30–40% left-sided; 20% pancolitis. In long-standing disease mucosa appears atrophic and featureless; colon narrows and shortens."))
story.append(MCQ("UC = mucosal inflammation ONLY (except fulminant disease where deeper layers are affected). Crohn's = transmural."))
story.append(MCQ("Microscopy: Two features of chronicity — (1) crypt architectural distortion (bifid, reduced crypts); (2) basal plasma cells and lymphoid aggregates. (Harrison's 22e)"))
story.append(H2("MONTREAL CLASSIFICATION (Exam Favorite — Harrison's 22e)"))
story.append(tbl(
    [Paragraph('<b>Class</b>', body_s), Paragraph('<b>Extent / Severity</b>', body_s)],
    [
        [Paragraph('E1: Proctitis', body_s), Paragraph('Involvement limited to rectum', body_s)],
        [Paragraph('E2: Left-sided UC', body_s), Paragraph('Distal to splenic flexure', body_s)],
        [Paragraph('E3: Pancolitis', body_s), Paragraph('Extends proximal to splenic flexure', body_s)],
        [Paragraph('S0: Remission', body_s), Paragraph('No symptoms', body_s)],
        [Paragraph('S1: Mild', body_s), Paragraph('≤4 stools/day, no systemic illness, normal ESR', body_s)],
        [Paragraph('S2: Moderate', body_s), Paragraph('≥4 stools/day, minimal systemic toxicity', body_s)],
        [Paragraph('S3: Severe', body_s), Paragraph('≥6 bloody stools/day, HR ≥90, Temp ≥37.5°C, Hb <10.5, ESR ≥30', body_s)],
    ],
    [4.5*cm, 11.5*cm]
))
story.append(H2("CLINICAL FEATURES"))
story.append(MCQ("Cardinal symptom = bloody diarrhea with mucus."))
story.append(bp("Proctitis:", "Fresh blood/mucus; tenesmus; urgency; rarely abdominal pain; constipation may occur from proximal slowing."))
story.append(bp("Left-sided/pancolitis:", "Bloody watery diarrhea; nocturnal and/or postprandial diarrhea; weight loss; fever."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("pANCA positive in ~70% of UC; ASCA positive in ~60% of Crohn's."))
story.append(bp("Endoscopy:", "Flexible sigmoidoscopy preferred in acute severe UC (NOT full colonoscopy — perforation risk)."))
story.append(bp("Histology:", "Crypt abscesses, goblet cell depletion, mucosal inflammation."))
story.append(H2("MANAGEMENT"))
story.append(MCQ("5-ASA (mesalazine) = cornerstone of mild-moderate UC treatment and maintenance."))
story.append(MCQ("Rescue therapy for acute severe UC unresponsive to IV steroids at 72 hrs: IV Ciclosporin OR Infliximab."))
story.append(MCQ("Surgery (proctocolectomy + IPAA) = CURATIVE for UC — the only cure."))
story.append(bp("Mild-Moderate:", "Mesalazine topical (suppositories/enemas) ± oral; steroids for flares."))
story.append(bp("Severe (inpatient):", "IV hydrocortisone 100 mg TDS; if no response at 72 hrs → IV ciclosporin or infliximab → colectomy."))
story.append(bp("Biologics:", "Infliximab, adalimumab (anti-TNF); vedolizumab (anti-integrin); ustekinumab (anti-IL-12/23); tofacitinib (JAK inhibitor)."))
story.append(HR())

# ════════════════════════════ Q10 ══════════════════════════════
story.append(Q(10, "Celiac Disease in Adults"))
story.append(REF("2759", "819"))
story.append(H2("DEFINITION (Harrison's 22e)"))
story.append(P("Celiac disease (celiac sprue/gluten-sensitive enteropathy) — immune response to gluten (gliadin fraction from wheat, rye, barley) → autoantibodies to tissue transglutaminase → villous atrophy. Tissue transglutaminase deamidates gluten → enhanced antigen presentation."))
story.append(MCQ("Genetics: HLA-DQ2 (90%) and HLA-DQ8 (10%). HLA-DQ2/DQ8 found in 25–35% of general population — most carriers do NOT develop celiac. A NEGATIVE test has NPV >99% — useful to RULE OUT celiac. (Harrison's 22e)"))
story.append(MCQ("Prevalence: Global 1.4%. 10–15% prevalence in first-degree relatives."))
story.append(H2("PATHOLOGY"))
story.append(MCQ("Marsh Classification: I (increased IELs) → II (+ crypt hyperplasia) → IIIa/b/c (partial/subtotal/total villous atrophy). Marsh IIIc = total villous atrophy."))
story.append(H2("CLINICAL FEATURES (Harrison's 22e)"))
story.append(MCQ("Most common presentation in ADULTS = Iron-deficiency anemia (duodenal involvement impairs iron absorption). NOT diarrhea (more common in children)."))
story.append(MCQ("Dermatitis herpetiformis: Intensely itchy vesicular rash (elbows, knees, buttocks) — PATHOGNOMONIC skin manifestation of celiac disease. Mediated by IgA deposits in skin."))
story.append(bp("Classic (children):", "Diarrhea, steatorrhea, weight loss, failure to thrive, bloating."))
story.append(bp("Non-classic (adults):", "Iron-deficiency anemia, osteoporosis, peripheral neuropathy, ataxia, migraine, infertility, elevated LFTs, short stature."))
story.append(bp("Associated conditions:", "Type 1 DM; autoimmune thyroid disease; Down syndrome; Turner syndrome — all have increased risk of celiac."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("Screening test of choice: Anti-tissue transglutaminase IgA (TTG-IgA). Must check total serum IgA first — 2–3% have IgA deficiency → false negative."))
story.append(MCQ("If IgA deficient: use TTG-IgG or anti-deamidated gliadin peptide IgG (DGP-IgG)."))
story.append(MCQ("Confirmatory test: Duodenal/jejunal biopsy (endoscopy) — multiple biopsies from 2nd/3rd part duodenum. Tests MUST be done on a GLUTEN-CONTAINING diet."))
story.append(MCQ("HLA-DQ2/DQ8 NEGATIVE = virtually rules out celiac disease (NPV >99%)."))
story.append(H2("MANAGEMENT"))
story.append(MCQ("Lifelong strict gluten-free diet (GFD) — avoid WHEAT, BARLEY, RYE."))
story.append(bp("Supplements:", "Iron, folate, B12, Vitamin D + calcium (especially if osteoporosis)."))
story.append(bp("Monitor:", "Anti-tTG titers (fall on GFD); DEXA scan; annual review."))
story.append(MCQ("Refractory celiac → risk of EATL (Enteropathy-Associated T-cell Lymphoma) — most serious complication."))
story.append(HR())

# ════════════════════════════ Q11 ══════════════════════════════
story.append(Q(11, "Ulcerative Colitis vs Crohn's Disease — Comparison"))
story.append(REF("2597", "805"))
story.append(tbl(
    [Paragraph('<b>Feature</b>', body_s), Paragraph('<b>Ulcerative Colitis</b>', body_s), Paragraph('<b>Crohn\'s Disease</b>', body_s)],
    [
        [Paragraph('Location', body_s), Paragraph('COLORECTAL ONLY (rectum to colon)', body_s), Paragraph('ANY PART of GI (mouth to anus)', body_s)],
        [Paragraph('Distribution', body_s), Paragraph('CONTINUOUS (no skip lesions)', body_s), Paragraph('SKIP LESIONS (discontinuous)', body_s)],
        [Paragraph('Rectal involvement', body_s), Paragraph('ALWAYS (100%)', body_s), Paragraph('Spared in ~50%', body_s)],
        [Paragraph('Depth', body_s), Paragraph('Mucosa ONLY', body_s), Paragraph('TRANSMURAL (full thickness)', body_s)],
        [Paragraph('Granulomas', body_s), Paragraph('ABSENT', body_s), Paragraph('Present (non-caseating) ~50%', body_s)],
        [Paragraph('Fistulae', body_s), Paragraph('Rare', body_s), Paragraph('Common (perianal, enteroenteric)', body_s)],
        [Paragraph('Perianal disease', body_s), Paragraph('Rare', body_s), Paragraph('COMMON (fissures, fistulae, abscess)', body_s)],
        [Paragraph('Cobblestone mucosa', body_s), Paragraph('Absent', body_s), Paragraph('PRESENT', body_s)],
        [Paragraph('Strictures', body_s), Paragraph('Rare', body_s), Paragraph('Common', body_s)],
        [Paragraph('Bleeding', body_s), Paragraph('PROMINENT, common', body_s), Paragraph('Less common', body_s)],
        [Paragraph('B12 deficiency', body_s), Paragraph('Not typical', body_s), Paragraph('Yes (terminal ileum)', body_s)],
        [Paragraph('Smoking', body_s), Paragraph('PROTECTIVE', body_s), Paragraph('RISK FACTOR', body_s)],
        [Paragraph('Serology', body_s), Paragraph('pANCA+ (~70%)', body_s), Paragraph('ASCA+ (~60%)', body_s)],
        [Paragraph('Surgery', body_s), Paragraph('CURATIVE (colectomy)', body_s), Paragraph('NOT CURATIVE (recurrence)', body_s)],
        [Paragraph('Cancer risk', body_s), Paragraph('Higher (CRC)', body_s), Paragraph('Present but lower', body_s)],
    ],
    [4.5*cm, 5.5*cm, 5.5*cm]
))
story.append(MCQ("Smoking PROTECTS against UC but is a RISK FACTOR for Crohn's — a classic MCQ trap."))
story.append(MCQ("Surgery CURES UC (proctocolectomy + IPAA) but does NOT cure Crohn's (high post-operative recurrence)."))
story.append(MCQ("Granulomas on biopsy → Crohn's (non-caseating). UC has NO granulomas."))
story.append(HR())

# ════════════════════════════ Q12 ══════════════════════════════
story.append(Q(12, "Tropical Sprue"))
story.append(REF("2765", "807"))
story.append(H2("DEFINITION (Harrison's 22e)"))
story.append(P("'Poorly understood syndrome manifested by chronic diarrhea, steatorrhea, weight loss, and nutritional deficiencies including both folate and vitamin B12. Malabsorption of two unrelated substances is required for diagnosis.' Occurs 8–20% of people with acute infectious gastroenteritis in India."))
story.append(MCQ("Geographic distribution: Southern India, Pakistan, Philippines, Puerto Rico, Haiti, Cuba. RARELY in Africa, Jamaica, or SE Asia."))
story.append(MCQ("Responds to antibiotics → evidence for infectious etiology. Incidence DECLINING due to improved sanitation."))
story.append(H2("ETIOLOGY"))
story.append(P("Presumed infectious. Consensus: one or more infectious agents (E. coli, Klebsiella, Enterobacter). Harrison's 22e: 'Because tropical sprue responds to antibiotics, the consensus is that it may be caused by one or more infectious agents.'"))
story.append(H2("CLINICAL FEATURES"))
story.append(MCQ("Folate absorbed EXCLUSIVELY in duodenum and proximal jejunum → most patients have folate malabsorption early. B12 deficiency comes later (ileal involvement)."))
story.append(bp("Symptoms:", "Chronic diarrhea, steatorrhea, weight loss, fatigue, abdominal cramps."))
story.append(bp("Nutritional:", "Megaloblastic anemia (folate early, B12 late); glossitis; stomatitis; edema."))
story.append(H2("DIAGNOSIS (Harrison's 22e)"))
story.append(MCQ("Diagnosis = abnormal small-intestinal biopsy in a person with chronic diarrhea + malabsorption who lives in/visited a tropical country."))
story.append(MCQ("Biopsy: PARTIAL villous atrophy (vs celiac which can be TOTAL). Similar severity throughout small intestine. Gluten-free diet does NOT improve tropical sprue."))
story.append(bp("Key distinction:", "Anti-tTG NEGATIVE (distinguishes from celiac disease)."))
story.append(H2("MANAGEMENT (Harrison's 22e)"))
story.append(MCQ("Treatment: Tetracycline (broad-spectrum antibiotic) × UP TO 6 MONTHS + Folic acid. Improvement within 1–2 weeks."))
story.append(bp("Folic acid:", "Alone induces hematologic remission + weight gain + partial histologic improvement."))
story.append(bp("Vitamin B12:", "If deficient, supplement parenterally."))
story.append(HR())

# ════════════════════════════ Q13 ══════════════════════════════
story.append(Q(13, "Upper GI Bleed / Hematemesis — Full Clinical Management"))
story.append(REF("360", "782"))
story.append(H2("TERMINOLOGY (Harrison's 22e)"))
story.append(MCQ("Melena = blood in GI tract for ≥14 h (and up to 3–5 days). More proximal bleed → more likely melena."))
story.append(MCQ("Hemoglobin DOES NOT FALL IMMEDIATELY with acute GIB — 'people bleed whole blood'. Hb may be normal at initial presentation. Takes up to 72 hrs to equilibrate."))
story.append(MCQ("Transfuse when Hb <7 g/dL — restrictive strategy shown to DECREASE rebleeding and death vs Hb <9 g/dL threshold (RCT — Harrison's 22e)."))
story.append(H2("GLASGOW-BLATCHFORD SCORE (GBS)"))
story.append(MCQ("GBS = 0 → patient can be managed as OUTPATIENT. Key components: BUN, Hb, SBP, HR, melena, syncope, liver disease, cardiac failure."))
story.append(H2("FORREST CLASSIFICATION (Endoscopic — Peptic Ulcer)"))
story.append(tbl(
    [Paragraph('<b>Class</b>', body_s), Paragraph('<b>Finding</b>', body_s), Paragraph('<b>Rebleed Risk</b>', body_s), Paragraph('<b>Action</b>', body_s)],
    [
        [Paragraph('Ia', body_s), Paragraph('Active spurting', body_s), Paragraph('~55%', body_s), Paragraph('Endoscopic Rx', body_s)],
        [Paragraph('Ib', body_s), Paragraph('Active oozing', body_s), Paragraph('~55%', body_s), Paragraph('Endoscopic Rx', body_s)],
        [Paragraph('IIa', body_s), Paragraph('Non-bleeding visible vessel', body_s), Paragraph('~43%', body_s), Paragraph('Endoscopic Rx', body_s)],
        [Paragraph('IIb', body_s), Paragraph('Adherent clot', body_s), Paragraph('~22%', body_s), Paragraph('Treat or observe', body_s)],
        [Paragraph('IIc', body_s), Paragraph('Flat pigmented spot', body_s), Paragraph('~10%', body_s), Paragraph('Observe; oral PPI', body_s)],
        [Paragraph('III', body_s), Paragraph('Clean base', body_s), Paragraph('~5%', body_s), Paragraph('Discharge possible', body_s)],
    ],
    [2*cm, 5*cm, 3*cm, 4.5*cm]
))
story.append(MCQ("Harrison's 22e: Patients with clean-based ulcers (Forrest III) have rebleeding rates approaching ZERO — can be discharged home after endoscopy if stable."))
story.append(H2("MANAGEMENT STEPS"))
story.append(MCQ("High-dose PPI (IV infusion) after endoscopic therapy for high-risk ulcers — decreases FURTHER BLEEDING and MORTALITY (multiple RCT meta-analysis, Harrison's 22e)."))
story.append(bp("1. Resuscitation:", "ABC. Two large-bore IV lines. Crossmatch. Vital signs."))
story.append(bp("2. Transfuse:", "Restrictive strategy — Hb target 7–8 g/dL."))
story.append(bp("3. IV PPI:", "Omeprazole/Pantoprazole infusion. Meta-analysis: constant infusion vs intermittent — outcomes comparable."))
story.append(bp("4. Endoscopy:", "Within 24 hrs for most; 6–12 hrs if hemodynamically unstable."))
story.append(bp("5. Endoscopic Rx:", "Dual therapy — adrenaline injection (1:10,000) + thermal (heater probe) or mechanical (clips)."))
story.append(bp("6. Embolization:", "Interventional radiology if endoscopy fails."))
story.append(bp("7. Surgery:", "Last resort — oversewing of bleeding vessel; Billroth procedure."))
story.append(P("For variceal bleed: See Q2 above."))
story.append(HR())

# ════════════════════════════ Q14 ══════════════════════════════
story.append(Q(14, "Extraintestinal Manifestations (EIM) of IBD/UC"))
story.append(REF("2604", "814"))
story.append(MCQ("EIM occur in ~25–35% of IBD patients. More common in Crohn's than UC."))
story.append(H2("A. PARALLEL DISEASE ACTIVITY (flare = worsening EIM)"))
story.append(bp("Peripheral arthropathy:", "Type 1 — pauciarticular (<5 joints), large joints; Type 2 — polyarticular (≥5 small joints)."))
story.append(bp("Erythema nodosum:", "Tender, raised, red nodules on shins. Most common IBD skin EIM."))
story.append(bp("Episcleritis:", "Painless redness of eye (scleral vessels). Correlates with disease activity."))
story.append(bp("Aphthous mouth ulcers:", "Correlate with bowel disease activity."))
story.append(H2("B. INDEPENDENT OF DISEASE ACTIVITY"))
story.append(MCQ("Ankylosing spondylitis (AS): HLA-B27 associated. Inflammatory back pain. Present in 2–3% of IBD. INDEPENDENT of bowel activity."))
story.append(MCQ("Pyoderma gangrenosum: Painful deep ulcers on lower limbs/periostomal. Treat with systemic steroids ± biologics. NOT needs IBD flare to occur."))
story.append(MCQ("Uveitis/Iritis: Painful, red eye + visual disturbance + photophobia. URGENT ophthalmology referral. INDEPENDENT of bowel activity."))
story.append(MCQ("Primary Sclerosing Cholangitis (PSC): MOST CHARACTERISTIC hepatobiliary EIM. 70–80% of PSC patients have UC. 'Beads on a string' = ERCP/MRCP appearance. Onion-skin periductal fibrosis. Risk of cholangiocarcinoma."))
story.append(H2("C. METABOLIC / OTHER"))
story.append(bp("Osteoporosis:", "Steroids + malabsorption of calcium + Vitamin D."))
story.append(bp("Thromboembolic disease:", "IBD = hypercoagulable state → PE, DVT."))
story.append(bp("Gallstones:", "Ileal disease (Crohn's) → bile salt malabsorption → cholesterol stones."))
story.append(bp("Oxalate renal stones:", "Crohn's > UC. Fat malabsorption → fatty acids bind calcium → free oxalate absorbed in colon."))
story.append(bp("Secondary amyloidosis:", "Rare; chronic inflammation → SAA protein deposition."))
story.append(HR())

# ════════════════════════════ Q15 ══════════════════════════════
story.append(Q(15, "Chronic Pancreatitis"))
story.append(REF("2795", "839"))
story.append(H2("DEFINITION & OVERVIEW (Harrison's 22e)"))
story.append(P("Chronic progressive inflammatory disease with irreversible structural damage. Harrison's 22e: 'There are currently no therapies to reverse or delay disease progression of chronic pancreatitis — management is primarily focused on screening for and management of disease-related complications.'"))
story.append(H2("CAUSES (TIGAR-O)"))
story.append(MCQ("Alcohol = MOST COMMON cause (70–80%). Smoking is an INDEPENDENT risk factor."))
story.append(bp("T — Toxic-metabolic:", "Alcohol (70–80%), smoking, hyperlipidemia, hypercalcemia, CRF."))
story.append(bp("I — Idiopathic"))
story.append(MCQ("G — Genetic: PRSS1 (hereditary pancreatitis — autosomal dominant); CFTR (cystic fibrosis); SPINK1 mutations. These are frequent exam MCQ choices."))
story.append(bp("A — Autoimmune:", "IgG4-related autoimmune pancreatitis (AIP Type 1). Responds to steroids."))
story.append(bp("R — Recurrent/severe acute pancreatitis"))
story.append(bp("O — Obstructive:", "Pancreatic duct stricture, divisum, tumor."))
story.append(H2("CLINICAL FEATURES"))
story.append(MCQ("Steatorrhea occurs when >90% of exocrine function is lost — because pancreas has HUGE reserve capacity."))
story.append(MCQ("Diabetes mellitus (Type 3c) — endocrine insufficiency; late feature; brittle diabetes."))
story.append(bp("Pain:", "Chronic epigastric radiating to back; worse with meals/alcohol; relieved by sitting forward; may burn out over years."))
story.append(H2("INVESTIGATIONS"))
story.append(MCQ("Pancreatic calcification on CT or plain AXR = PATHOGNOMONIC of chronic pancreatitis."))
story.append(MCQ("Fecal elastase-1 = best non-invasive test for exocrine pancreatic insufficiency. <100 μg/g = severe insufficiency."))
story.append(bp("ERCP:", "'Chain of lakes' appearance — alternating ductal strictures and dilations."))
story.append(bp("EUS:", "Most sensitive for early disease."))
story.append(H2("COMPLICATIONS (Harrison's Table 339-7)"))
story.append(bp("Chronic abdominal pain; exocrine insufficiency; diabetes; splanchnic venous thrombosis."))
story.append(bp("Biliary stricture/cirrhosis; pancreatic duct stricture; pseudocyst."))
story.append(MCQ("Pancreatic cancer risk increased 10-fold in chronic pancreatitis."))
story.append(H2("MANAGEMENT (Harrison's 22e)"))
story.append(MCQ("Steatorrhea treatment: Pancreatic enzyme replacement therapy (PERT) = cornerstone. Start 25,000–50,000 units lipase per meal; may increase to 100,000 units. Give with fat-soluble vitamin supplements."))
story.append(MCQ("PPI may be needed alongside PERT to prevent acid inactivation of enzymes."))
story.append(bp("Pain:", "Step-up — paracetamol → NSAIDs → tramadol → opioids → celiac plexus block."))
story.append(bp("Surgery:", "Puestow (dilated duct); Beger/Frey; Whipple's (if malignancy suspected)."))
story.append(bp("Stop alcohol + smoking:", "MOST IMPORTANT step — slows progression."))
story.append(HR())

# ════════════════════════════ Q16 ══════════════════════════════
story.append(Q(16, "Zollinger-Ellison Syndrome (ZES)"))
story.append(REF("2577", "802"))
story.append(H2("DEFINITION (Harrison's 22e)"))
story.append(P("'Severe peptic ulcer diathesis secondary to gastric acid hypersecretion due to unregulated gastrin release from a non-β-cell, often well-differentiated neuroendocrine tumor (NET; gastrinoma).' Comprises 0.1–1% of PUD. Diagnosis often delayed 4–7 years after symptom onset."))
story.append(MCQ("Gastrinoma triangle: Bounded by (1) confluence of cystic duct and CBD superiorly, (2) junction of 2nd and 3rd duodenum inferiorly, (3) neck/body of pancreas medially. 60–90% of gastrinomas found here."))
story.append(MCQ("Duodenal gastrinomas = MOST COMMON non-pancreatic site. Smaller, slower growing, less likely to metastasize."))
story.append(MCQ("25–30% of ZES is associated with MEN-1 (Multiple Endocrine Neoplasia Type 1 = Pituitary + Parathyroid + Pancreatic NETs)."))
story.append(MCQ(">60% of gastrinomas are malignant. Up to 30–50% have metastatic disease at presentation."))
story.append(H2("CLINICAL FEATURES (Harrison's 22e)"))
story.append(MCQ("Peptic ulcer is the MOST COMMON clinical manifestation — occurs in >90% of gastrinoma patients."))
story.append(bp("Suspicion criteria:", "Ulcers in UNUSUAL locations (2nd part duodenum, jejunum); refractory to standard therapy; ulcer recurrence post acid-reducing surgery; ulcers with frank GI bleed."))
story.append(MCQ("Diarrhea + steatorrhea: High acid inactivates pancreatic enzymes + precipitates bile salts → malabsorption."))
story.append(bp("Severe GERD/esophagitis:", "Prominent gastric rugae on endoscopy."))
story.append(H2("INVESTIGATIONS (Harrison's 22e)"))
story.append(MCQ("Fasting serum gastrin >1000 pg/mL (normal <100 pg/mL) WITH gastric pH <2 = diagnostic of ZES. PPIs cause elevated gastrin — stop for ≥1 week before testing."))
story.append(MCQ("Secretin stimulation test: If fasting gastrin 100–1000 pg/mL → IV secretin → paradoxical RISE in gastrin >200 pg/mL above baseline = positive for ZES (secretin normally INHIBITS gastrin)."))
story.append(bp("Tumor localization:", "EUS (best for pancreatic); CT/MRI; Somatostatin receptor scintigraphy (Octreotide scan); PET-CT."))
story.append(H2("MANAGEMENT"))
story.append(MCQ("High-dose PPI (omeprazole 60–80 mg/day) = mainstay of medical therapy for acid control."))
story.append(bp("Surgery:", "Curative resection if localized and no MEN-1 (can cure up to 40% of sporadic ZES)."))
story.append(bp("MEN-1 + ZES:", "Surgery rarely curative; medical management with high-dose PPI preferred."))
story.append(bp("Metastatic disease:", "Somatostatin analogues (octreotide/lanreotide) + chemotherapy (streptozotocin + 5-FU or temozolomide)."))
story.append(HR())

# ════════════════════════════ Q17 ══════════════════════════════
story.append(Q(17, "Role of H. pylori in Gastroduodenal Diseases"))
story.append(REF("2569", "791"))
story.append(H2("OVERVIEW"))
story.append(P("Gram-negative, spiral, microaerophilic bacterium. Colonizes gastric mucosa under mucus layer. Urease-producing → converts urea to ammonia → neutralizes local acid → allows bacterial survival. Global prevalence ~50% (higher in developing world)."))
story.append(MCQ("H. pylori = WHO Group 1 carcinogen (definite human carcinogen)."))
story.append(MCQ("Virulence factors: CagA (cytotoxin-associated gene A) = injected into epithelial cells → oncogenic signaling; VacA (vacuolating cytotoxin) → cell vacuolation and apoptosis."))
story.append(H2("DISEASES"))
story.append(MCQ("1. Chronic active GASTRITIS (Type B, antral-predominant): Present in almost ALL H. pylori-infected individuals."))
story.append(MCQ("2. Duodenal ulcer: 90–95% H. pylori positive. Eradication → recurrence from 67% to <10–20% (Harrison's 22e)."))
story.append(MCQ("3. Gastric ulcer: 70–75% H. pylori positive."))
story.append(MCQ("4. Gastric ADENOCARCINOMA: Correa cascade: H. pylori → chronic gastritis → atrophy → intestinal metaplasia → dysplasia → cancer. 6x increased risk."))
story.append(MCQ("5. Gastric MALToma: 60–90% of gastric MALT lymphomas achieve COMPLETE REMISSION with H. pylori eradication alone (Harrison's 22e)."))
story.append(bp("6. ITP (Idiopathic thrombocytopenic purpura):", "ACG guidelines: test and eradicate H. pylori. Mechanism unclear but platelet counts improve with eradication."))
story.append(bp("7. Iron-deficiency anemia:", "H. pylori impairs iron absorption. ACG: test and treat H. pylori in unexplained IDA."))
story.append(H2("DIAGNOSIS"))
story.append(tbl(
    [Paragraph('<b>Test</b>', body_s), Paragraph('<b>Sensitivity</b>', body_s), Paragraph('<b>Key Points</b>', body_s)],
    [
        [Paragraph('Urea breath test (13C-UBT)', body_s), Paragraph('95%', body_s), Paragraph('NON-INVASIVE gold standard. Stop PPI 2 wks before. Test of choice for post-treatment confirmation.', body_s)],
        [Paragraph('Stool antigen test', body_s), Paragraph('94%', body_s), Paragraph('Non-invasive. Stop PPI 2 wks before. Good for follow-up.', body_s)],
        [Paragraph('CLO (rapid urease) test', body_s), Paragraph('90–95%', body_s), Paragraph('Requires biopsy at endoscopy.', body_s)],
        [Paragraph('Histology', body_s), Paragraph('90%', body_s), Paragraph('From biopsy; Giemsa/Warthin-Starry stain.', body_s)],
        [Paragraph('Serology (IgG)', body_s), Paragraph('85%', body_s), Paragraph('CANNOT confirm active infection. Persists after eradication — NOT for post-treatment testing.', body_s)],
    ],
    [4*cm, 3*cm, 8.5*cm]
))
story.append(MCQ("WHEN TO TEST AND TREAT (ACG/Maastricht VI): PUD; gastric MALToma; after early gastric cancer resection; unexplained IDA; ITP; uninvestigated dyspepsia in age <60 (test-and-treat strategy); first-degree relatives with gastric cancer."))
story.append(H2("ERADICATION THERAPY (Harrison's 22e)"))
story.append(MCQ("Triple therapy (1st line): PPI + Clarithromycin + Amoxicillin × 7–14 days. Increasing clarithromycin resistance is a major global problem."))
story.append(MCQ("Quadruple therapy (if failed/resistant): PPI + Bismuth + Metronidazole + Tetracycline × 10–14 days."))
story.append(bp("Confirm eradication:", "UBT or stool antigen — ≥4 weeks after completing antibiotics and ≥2 weeks after stopping PPI."))
story.append(HR())

# ════════════════════════════ Q18 ══════════════════════════════
story.append(Q(18, "Inflammatory Bowel Disease (IBD) — Types, Features & Management"))
story.append(REF("2593", "805"))
story.append(H2("OVERVIEW"))
story.append(P("IBD = Crohn's Disease + Ulcerative Colitis (+ IBD-Unclassified ~10%). Chronic relapsing-remitting conditions. Peak incidence 15–35 yrs (bimodal with 2nd peak at 50–70 yrs). Increasing worldwide, especially developing nations adopting western lifestyle."))
story.append(H2("PATHOGENESIS"))
story.append(MCQ("IBD = Dysregulated immune response to commensal gut microbiota in GENETICALLY SUSCEPTIBLE individuals."))
story.append(bp("NOD2 gene mutations:", "Most strongly associated with Crohn's disease (especially ileal Crohn's)."))
story.append(bp("HLA associations:", "HLA-DQ2/DQ8 with celiac; HLA-B27 with ankylosing spondylitis (IBD EIM)."))
story.append(bp("Key cytokines:", "TNF-alpha (major therapeutic target); IL-12/23 pathway (Crohn's); IL-13 (UC)."))
story.append(MCQ("Risk factors: Family history (strongest risk factor); smoking (Crohn's risk factor; protective in UC); NSAIDs (can precipitate flare); antibiotics; appendectomy (protective in UC)."))
story.append(H2("CROHN'S DISEASE — CLINICAL FEATURES"))
story.append(bp("RLQ pain:", "Terminal ileitis — may mimic appendicitis. Classic presentation."))
story.append(bp("Diarrhea:", "May lack blood if small bowel only involved."))
story.append(MCQ("Perianal disease = characteristic feature of Crohn's (fistulae, skin tags, abscesses, fissures). Rare in UC."))
story.append(bp("Other:", "Malnutrition, growth retardation (children), obstructive symptoms, fistulae (enteroenteric, enterovesical, enterovaginal, enterocutaneous)."))
story.append(H2("UC — CLINICAL FEATURES"))
story.append(MCQ("Cardinal = BLOODY DIARRHEA WITH MUCUS + TENESMUS."))
story.append(bp("Proctitis:", "Fresh blood/mucus per rectum; tenesmus; constipation may occur (proximal stasis)."))
story.append(H2("MANAGEMENT — INDUCTION OF REMISSION"))
story.append(bp("Mild-Moderate UC:", "5-ASA (mesalazine) topical ± oral. Steroids (oral prednisolone) for flares."))
story.append(bp("Severe UC:", "IV hydrocortisone 100 mg TDS; rescue: IV ciclosporin or infliximab; if fails → colectomy."))
story.append(bp("Crohn's:", "Corticosteroids; budesonide (ileal/right-sided); elemental diet (especially children)."))
story.append(H2("MAINTENANCE OF REMISSION"))
story.append(bp("UC:", "Mesalazine (5-ASA); azathioprine/6-MP (steroid-sparing)."))
story.append(bp("Crohn's:", "Azathioprine/6-MP; methotrexate; no role for 5-ASA."))
story.append(H2("BIOLOGICS (Harrison's 22e — Current Standard of Care)"))
story.append(tbl(
    [Paragraph('<b>Drug</b>', body_s), Paragraph('<b>Mechanism</b>', body_s), Paragraph('<b>Indication</b>', body_s)],
    [
        [Paragraph('Infliximab, Adalimumab, Golimumab', body_s), Paragraph('Anti-TNF-α', body_s), Paragraph('UC + Crohn\'s', body_s)],
        [Paragraph('Vedolizumab', body_s), Paragraph('Anti-α4β7 integrin (gut-selective)', body_s), Paragraph('UC + Crohn\'s', body_s)],
        [Paragraph('Ustekinumab', body_s), Paragraph('Anti-IL-12/23 (p40 subunit)', body_s), Paragraph("Crohn's + UC", body_s)],
        [Paragraph('Risankizumab', body_s), Paragraph('Anti-IL-23 (p19 subunit)', body_s), Paragraph("Crohn's", body_s)],
        [Paragraph('Tofacitinib, Upadacitinib', body_s), Paragraph('JAK inhibitor (pan-JAK/JAK1)', body_s), Paragraph('UC', body_s)],
    ],
    [5*cm, 5*cm, 5.5*cm]
))
story.append(MCQ("Vedolizumab = GUT-SELECTIVE (anti-α4β7 integrin) — fewer systemic immunosuppressive side effects vs anti-TNF."))
story.append(MCQ("Ustekinumab acts on BOTH IL-12 AND IL-23 via the shared p40 subunit."))
story.append(H2("SURGERY"))
story.append(MCQ("UC: Proctocolectomy + IPAA (J-pouch) = CURATIVE. 'Cure' not achievable with medical therapy alone."))
story.append(bp("Crohn's:", "Resection NOT curative (high recurrence). Stricturoplasty preserves bowel length."))
story.append(H2("SURVEILLANCE"))
story.append(bp("CRC colonoscopy:", "UC — every 1–5 years based on extent and duration (earlier with PSC)."))
story.append(bp("Fecal calprotectin:", "Non-invasive surrogate marker of mucosal inflammation; useful for monitoring."))

# ── FOOTER ─────────────────────────────────────────────────────────────────
story.append(SP(10))
story.append(HRFlowable(width="100%", thickness=1.5, color=NAVY, spaceAfter=6))
story.append(Paragraph(
    "References: Harrison's Principles of Internal Medicine 22nd Edition (2025, McGraw-Hill) | "
    "Davidson's Principles & Practice of Medicine 23rd Edition | "
    "Yamada's Textbook of Gastroenterology 7th Ed.",
    note_s
))
story.append(Paragraph(
    "⭐ = MCQ High-Yield Point  |  🔑 = Key Exam Fact  |  Created for exam preparation purposes.",
    note_s
))

doc.build(story)
print(f"PDF built: {OUTPUT}")