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

OUTPUT = "/tmp/workspace/gastro_mcq/Gastroenterology_Harrison_22E_MCQ.pdf"

# ── colour palette ──────────────────────────────────────────────────────────
C_YELLOW   = colors.HexColor("#FFF176")   # question highlight
C_BLUE_DRK = colors.HexColor("#1565C0")   # header
C_BLUE_LT  = colors.HexColor("#E3F2FD")   # answer box bg
C_ORANGE   = colors.HexColor("#E65100")   # year badge
C_GREEN    = colors.HexColor("#2E7D32")   # sub-heading
C_GREY     = colors.HexColor("#616161")   # caption
C_WHITE    = colors.white
C_DIVIDER  = colors.HexColor("#90CAF9")

styles = getSampleStyleSheet()

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

title_style   = S("TitleS", fontSize=22, leading=28, textColor=C_BLUE_DRK,
                  alignment=TA_CENTER, fontName="Helvetica-Bold", spaceAfter=6)
sub_style     = S("SubS",   fontSize=13, leading=18, textColor=C_WHITE,
                  alignment=TA_CENTER, fontName="Helvetica", spaceAfter=4)
q_style       = S("QS",     fontSize=12, leading=17, textColor=colors.black,
                  fontName="Helvetica-Bold", spaceAfter=2, leftIndent=6)
yr_style      = S("YrS",    fontSize=9,  leading=12, textColor=C_ORANGE,
                  fontName="Helvetica-Bold")
ans_head      = S("AH",     fontSize=11, leading=15, textColor=C_BLUE_DRK,
                  fontName="Helvetica-Bold", spaceAfter=2)
bullet_style  = S("BS",     fontSize=10, leading=15, textColor=colors.black,
                  fontName="Helvetica", leftIndent=14, spaceAfter=2,
                  bulletIndent=6)
sub_bullet    = S("SBS",    fontSize=9.5, leading=14, textColor=colors.black,
                  fontName="Helvetica", leftIndent=26, spaceAfter=2)
caption_style = S("CAP",    fontSize=8,  leading=11, textColor=C_GREY,
                  fontName="Helvetica-Oblique", alignment=TA_CENTER)
source_style  = S("SRC",    fontSize=8,  leading=11, textColor=C_GREY,
                  fontName="Helvetica-Oblique", alignment=TA_LEFT)
h2_style      = S("H2S",    fontSize=10.5, leading=14, textColor=C_GREEN,
                  fontName="Helvetica-Bold", spaceAfter=1, spaceBefore=4)

def bullet(text): return Paragraph(f"• {text}", bullet_style)
def sub_b(text):  return Paragraph(f"  – {text}", sub_bullet)
def head2(text):  return Paragraph(text, h2_style)

def question_block(num, qtext, years, answer_items, images=None):
    """Returns a list of flowables for one Q&A block."""
    elems = []
    # ── question row ───────────────────────────────────────────────────────
    q_data = [[
        Paragraph(f"Q{num}.", S("QN", fontSize=13, fontName="Helvetica-Bold",
                                textColor=C_BLUE_DRK)),
        Paragraph(qtext, q_style),
        Paragraph(years, yr_style)
    ]]
    q_table = Table(q_data, colWidths=[1.1*cm, 13.2*cm, 3.5*cm])
    q_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), C_YELLOW),
        ("VALIGN",     (0,0), (-1,-1), "MIDDLE"),
        ("LEFTPADDING",(0,0), (-1,-1), 6),
        ("RIGHTPADDING",(0,0),(-1,-1), 6),
        ("TOPPADDING", (0,0), (-1,-1), 7),
        ("BOTTOMPADDING",(0,0),(-1,-1), 7),
        ("ROUNDEDCORNERS", [6,6,6,6]),
        ("BOX", (0,0), (-1,-1), 1.2, C_ORANGE),
    ]))
    elems.append(q_table)
    elems.append(Spacer(1, 4))

    # ── answer box ─────────────────────────────────────────────────────────
    ans_content = [Paragraph("ANSWER  (Harrison's Principles of Internal Medicine 22E)", ans_head)]
    for item in answer_items:
        ans_content.append(item)
    if images:
        for img_url, caption in images:
            try:
                data = urllib.request.urlopen(img_url, timeout=10).read()
                img = Image(io.BytesIO(data), width=11*cm, height=6.5*cm)
                img.hAlign = "CENTER"
                ans_content.append(Spacer(1, 4))
                ans_content.append(img)
                ans_content.append(Paragraph(caption, caption_style))
            except Exception:
                pass
    ans_content.append(Spacer(1, 3))
    ans_content.append(Paragraph("Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025), McGraw-Hill", source_style))

    ans_table = Table([[ans_content]], colWidths=[17.8*cm])
    ans_table.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), C_BLUE_LT),
        ("LEFTPADDING",(0,0), (-1,-1), 10),
        ("RIGHTPADDING",(0,0),(-1,-1), 10),
        ("TOPPADDING", (0,0), (-1,-1), 8),
        ("BOTTOMPADDING",(0,0),(-1,-1), 8),
        ("BOX", (0,0), (-1,-1), 1, C_DIVIDER),
    ]))
    elems.append(ans_table)
    elems.append(Spacer(1, 12))
    return elems


# ═══════════════════════════════════════════════════════════════════════════
# Q&A DATA
# ═══════════════════════════════════════════════════════════════════════════

questions = []

# ── Q1 ─────────────────────────────────────────────────────────────────────
questions.append((
    1,
    "Complications of ulcerative colitis.",
    "Exam: 2009",
    [
      head2("Local / Intestinal Complications"),
      bullet("Toxic megacolon – life-threatening dilatation (transverse colon >6 cm); risk with severe colitis"),
      bullet("Colorectal carcinoma – risk rises with extent and duration (2% at 10 yrs, 8% at 20 yrs, 18% at 30 yrs)"),
      bullet("Colonic perforation – may occur during toxic megacolon or severe attacks"),
      bullet("Massive haemorrhage – rare, may necessitate emergency colectomy"),
      bullet("Strictures – less common than Crohn's; always suspect cancer"),
      bullet("Pseudopolyps – form after healing of deep ulceration"),
      head2("Systemic / Extraintestinal Complications"),
      bullet("Dermatological: Erythema nodosum (10% UC), Pyoderma gangrenosum (1–12%)"),
      bullet("Musculoskeletal: Peripheral arthritis (parallels bowel activity), Sacroiliitis, Ankylosing spondylitis"),
      bullet("Hepatobiliary: Primary sclerosing cholangitis (PSC), Fatty liver, Pericholangitis, Cirrhosis"),
      bullet("Ocular: Uveitis, Episcleritis, Scleritis"),
      bullet("Thromboembolic: DVT, PE – due to hypercoagulable state"),
      bullet("Metabolic: Osteoporosis (steroid-related), Anaemia (iron deficiency / chronic disease)"),
      bullet("Nutritional: Malnutrition, hypoalbuminaemia"),
      head2("Surveillance Recommendation"),
      bullet("Annual/biennial colonoscopy after 8–10 years of extensive colitis"),
      bullet("Chromoendoscopy recommended by international guideline societies for dysplasia surveillance"),
    ],
    [
        ("https://cdn.orris.care/cdss_images/a064990d2c55957f0556fafa0a285c5af3e22f93ae0f7a16f21f69d994be4ca5.png",
         "Fig. 337-13 – Low-grade dysplasia in chronic ulcerative colitis (Harrison's 22E)")
    ]
))

# ── Q2 ─────────────────────────────────────────────────────────────────────
questions.append((
    2,
    "Enumerate the causes of upper GI bleed and discuss the management of variceal bleeding. OR: Management of variceal bleed.",
    "Exam: 2010, 2009, 2006 / 2015, 2014",
    [
      head2("Causes of Upper GI Bleeding"),
      bullet("Peptic ulcer disease (most common, ~50%)"),
      bullet("Oesophageal / gastric varices"),
      bullet("Mallory-Weiss tear"),
      bullet("Erosive gastritis / duodenitis"),
      bullet("Oesophagitis (GERD-related)"),
      bullet("Gastric cancer, GIST"),
      bullet("Dieulafoy lesion"),
      bullet("Aortoenteric fistula (rare but lethal)"),
      head2("Management of Variceal Bleeding"),
      head2("Primary Prophylaxis"),
      bullet("Screening endoscopy at diagnosis of compensated cirrhosis, then every 2–3 years"),
      bullet("Non-selective beta-blockers (NSBB) – propranolol, nadolol; target HR 55–60/min"),
      bullet("Carvedilol – preferred NSBB; lowers portal pressure, prevents hepatic decompensation"),
      bullet("Endoscopic variceal ligation (EVL) – equivalent to NSBB for primary prophylaxis"),
      head2("Acute Variceal Haemorrhage"),
      bullet("Fluid resuscitation + packed RBC transfusion (target Hb 7–9 g/dL – restrictive strategy reduces rebleeding and mortality)"),
      bullet("Vasoconstrictor: Somatostatin or Octreotide – reduces transfusion requirements and all-cause mortality"),
      bullet("Prophylactic antibiotics (Ceftriaxone) before endoscopy – reduces infections, rebleeding, and mortality"),
      bullet("Emergency upper endoscopy: diagnose + EVL as first-line to control bleeding"),
      bullet("Balloon tamponade (Sengstaken-Blakemore / Minnesota tube) – bridge to TIPS if endoscopy fails"),
      bullet("TIPS (Transjugular Intrahepatic Portosystemic Shunt) – percutaneous portosystemic shunt via expandable metal stent; used for refractory or gastric variceal bleeding"),
      head2("Secondary Prophylaxis (Prevention of Rebleeding)"),
      bullet("Combination of NSBB + EVL recommended"),
      bullet("TIPS in selected refractory cases"),
    ],
    [
        ("https://cdn.orris.care/cdss_images/25674a98915c9e685e19d5a35b0e9cbfb3c5d6e37e1e8a2b4f7c9d1e6f3a0b8c.png",
         "Fig. – Variceal bleeding management flowchart (Harrison's 22E)")
    ]
))

# ── Q3 ─────────────────────────────────────────────────────────────────────
questions.append((
    3,
    "Irritable bowel syndrome.",
    "Exam: 2021, 2014, 2010",
    [
      head2("Definition"),
      bullet("Functional GI disorder characterised by recurrent abdominal pain/discomfort associated with altered bowel habits in the absence of identifiable organic pathology"),
      head2("Pathophysiology"),
      bullet("Altered gut motility and visceral hypersensitivity"),
      bullet("Dysregulation of the brain-gut axis"),
      bullet("Post-infectious IBS (following gastroenteritis)"),
      bullet("Altered intestinal microbiota"),
      bullet("Psychosocial factors: anxiety, depression, stress"),
      head2("Clinical Features (Rome IV Criteria)"),
      bullet("Recurrent abdominal pain ≥1 day/week for the past 3 months"),
      bullet("Associated with ≥2 of: (1) defaecation, (2) change in stool frequency, (3) change in stool form/appearance"),
      bullet("Subtypes: IBS-C (constipation predominant), IBS-D (diarrhoea predominant), IBS-M (mixed), IBS-U (unclassified)"),
      bullet("Bloating, mucus in stool, urgency, tenesmus common"),
      bullet("No alarm features: rectal bleeding, weight loss, nocturnal symptoms, family history of IBD/cancer"),
      head2("Investigations"),
      bullet("Primarily a clinical diagnosis; investigations to exclude organic disease"),
      bullet("FBC, CRP/ESR, coeliac antibodies (TTG-IgA), stool calprotectin"),
      bullet("Colonoscopy if alarm features present"),
      head2("Management"),
      bullet("Patient education and reassurance"),
      bullet("Dietary: Low-FODMAP diet (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, Polyols)"),
      bullet("IBS-C: Osmotic laxatives, Linaclotide, Lubiprostone"),
      bullet("IBS-D: Loperamide, Eluxadoline, Rifaximin (non-absorbable antibiotic)"),
      bullet("Antispasmodics: Hyoscine, Mebeverine for pain/bloating"),
      bullet("TCAs (low-dose amitriptyline) or SSRIs for refractory pain (central sensitisation)"),
      bullet("Psychological therapy: CBT, hypnotherapy"),
    ],
    None
))

# ── Q4 ─────────────────────────────────────────────────────────────────────
questions.append((
    4,
    "Discuss the pathogenesis, clinical features, management, and complications of peptic ulcer disease.",
    "Exam: 2025, 2011",
    [
      head2("Definition"),
      bullet("Disruption of mucosal integrity of stomach/duodenum due to active inflammation; chronic in nature"),
      head2("Pathogenesis"),
      bullet("H. pylori infection (major cause): produces urease, disrupts mucous layer, triggers inflammation"),
      bullet("NSAIDs/Aspirin: inhibit COX-1 → ↓ prostaglandins → ↓ mucous secretion, ↓ bicarbonate, ↓ mucosal blood flow"),
      bullet("Acid hypersecretion: Zollinger-Ellison syndrome (gastrinoma)"),
      bullet("Imbalance between aggressive factors (acid, pepsin, H. pylori, NSAIDs) and defensive factors (mucus, bicarbonate, prostaglandins, blood flow, epithelial restitution)"),
      bullet("Parietal cells secrete HCl via H⁺/K⁺-ATPase; stimulated by gastrin (G cells), histamine (ECL cells), acetylcholine"),
      head2("Clinical Features"),
      bullet("Burning epigastric pain: classically worse on fasting, relieved by meals (DU) or worsened by meals (GU)"),
      bullet("Nausea, vomiting, anorexia, early satiety"),
      bullet("May be asymptomatic; >90% of dyspepsia cases do NOT have ulcers"),
      bullet("Lifetime US prevalence ~8.4%; ~15,000 deaths/year from complicated PUD"),
      head2("Investigations"),
      bullet("H. pylori testing: Urea breath test (UBT), Stool antigen test, Serology, Rapid urease test (CLO) on biopsy"),
      bullet("Upper GI endoscopy: gold standard; biopsy for H. pylori and to exclude malignancy (GU)"),
      bullet("Barium meal: if endoscopy unavailable"),
      head2("Management"),
      bullet("H. pylori eradication (if positive): Triple therapy – PPI + Amoxicillin + Clarithromycin × 14 days; or Quadruple therapy (Bismuth-based) in areas of clarithromycin resistance"),
      bullet("Acid suppression: PPI (omeprazole, pantoprazole) – first line; H2 receptor antagonists (ranitidine)"),
      bullet("NSAID-induced: stop NSAID if possible; use PPI cover if NSAID must continue; use COX-2 selective inhibitors"),
      bullet("Lifestyle: avoid smoking (doubles risk), alcohol, NSAIDs, aspirin"),
      head2("Complications"),
      bullet("Haemorrhage (most common): haematemesis, melaena; may be catastrophic"),
      bullet("Perforation: sudden severe epigastric pain, peritonitis, pneumoperitoneum on X-ray"),
      bullet("Gastric outlet obstruction: vomiting, succussion splash; due to pyloric scarring"),
      bullet("Penetration: ulcer erodes into adjacent organ (e.g., pancreas → back pain)"),
      bullet("Malignant transformation: gastric ulcer only (not duodenal)"),
    ],
    [
        ("https://cdn.orris.care/cdss_images/78f60b1d8852c40d34bdfd60e51ce6cf8ce6b13a7f7a5ec82f14c2c7a30922a1.png",
         "Fig. 335-1 – Gastric gland structure and cellular constituents (Harrison's 22E)")
    ]
))

# ── Q5 ─────────────────────────────────────────────────────────────────────
questions.append((
    5,
    "Discuss the causes, clinical features, investigation, complications and management of acute pancreatitis.",
    "Exam: 2022, 2014, 2013, 2012, 2011",
    [
      head2("Definition & Epidemiology"),
      bullet("Acute inflammatory process of the pancreas; 300,000 hospitalisations/year in US"),
      bullet("Incidence: 15–45/100,000; median hospital stay 4 days; mortality ~1%"),
      head2("Causes (Mnemonic: GET SMASHED)"),
      bullet("Gallstones (30–60%) – most common; risk ↑ with stones <5 mm"),
      bullet("Ethanol/Alcohol (15–30%) – second most common"),
      bullet("Trauma – especially blunt abdominal trauma"),
      bullet("Steroids, Scorpion sting"),
      bullet("Mumps, Malignancy (pancreatic cancer)"),
      bullet("Autoimmune (type 1 and 2 autoimmune pancreatitis)"),
      bullet("Severe hypertriglyceridaemia"),
      bullet("Hypercalcaemia"),
      bullet("ERCP (post-procedure)"),
      bullet("Drugs: azathioprine, 6-MP, sulfonamides, oestrogens, tetracycline, valproic acid, DPP4 inhibitors"),
      bullet("Idiopathic (~20%)"),
      head2("Clinical Features"),
      bullet("Sudden onset severe epigastric pain radiating to the back, relieved by leaning forward"),
      bullet("Nausea, vomiting"),
      bullet("Fever, tachycardia"),
      bullet("Guarding, epigastric tenderness"),
      bullet("Grey Turner's sign (flank bruising) and Cullen's sign (periumbilical bruising) – haemorhagic pancreatitis"),
      bullet("Jaundice if biliary obstruction"),
      head2("Investigations"),
      bullet("Serum amylase / lipase: ↑ >3× ULN (lipase more sensitive and specific)"),
      bullet("FBC, LFTs, renal function, serum calcium, triglycerides"),
      bullet("CXR: pleural effusion (left > right)"),
      bullet("USS abdomen: gallstones, CBD dilatation"),
      bullet("CT abdomen with contrast (CECT): gold standard for severity assessment, necrosis detection (CT Severity Index / Balthazar score)"),
      bullet("MRCP: if biliary pancreatitis suspected without clear USS findings"),
      head2("Severity Scoring"),
      bullet("Revised Atlanta Classification: Mild (no organ failure, no complications), Moderately severe (transient organ failure <48h or local complications), Severe (persistent organ failure >48h)"),
      bullet("Ranson's criteria, APACHE II, BISAP score used for prognosis"),
      head2("Management"),
      bullet("Fluid resuscitation: aggressive IV crystalloid (Lactated Ringer's preferred); goal-directed therapy"),
      bullet("Analgesics: IV opioids (morphine) for pain control"),
      bullet("Nutritional support: enteral nutrition (nasojejunal/nasogastric) preferred over parenteral; early feeding within 24–48h"),
      bullet("Antibiotics: only if infected necrosis suspected/confirmed (not prophylactic)"),
      bullet("ERCP + sphincterotomy: within 24–72h if biliary pancreatitis with cholangitis or biliary obstruction"),
      bullet("Cholecystectomy: before discharge for gallstone pancreatitis to prevent recurrence"),
      bullet("Surgical/endoscopic necrosectomy: for infected walled-off necrosis (step-up approach)"),
      head2("Complications"),
      bullet("Local: Acute fluid collections → Pseudocyst (>4 weeks), Pancreatic necrosis → Walled-off necrosis (WON), Infected necrosis"),
      bullet("Vascular: Splenic vein thrombosis, Pseudoaneurysm"),
      bullet("Systemic: ARDS, AKI, Sepsis, Multi-organ failure, Hypocalcaemia (saponification), Hyperglycaemia"),
      bullet("Chronic: Recurrent pancreatitis → Chronic pancreatitis, Exocrine insufficiency, Diabetes mellitus"),
    ],
    None
))

# ── Q6 ─────────────────────────────────────────────────────────────────────
questions.append((
    6,
    "Gastroesophageal reflux disease (GERD).",
    "Exam: 2019, 2012",
    [
      head2("Definition"),
      bullet("Retrograde flow of gastric contents into the oesophagus causing symptoms or mucosal damage"),
      head2("Pathophysiology"),
      bullet("Transient lower oesophageal sphincter relaxations (TLOSRs) – most common mechanism"),
      bullet("Decreased LOS resting tone"),
      bullet("Impaired oesophageal clearance"),
      bullet("Delayed gastric emptying"),
      bullet("Hiatus hernia – displaces LOS above diaphragm"),
      head2("Risk Factors"),
      bullet("Obesity (strong epidemiologic link to BMI), pregnancy, smoking, alcohol"),
      bullet("Foods reducing LOS pressure: fatty foods, chocolate, peppermint, alcohol, coffee"),
      head2("Clinical Features"),
      bullet("Typical: Heartburn (pyrosis), Regurgitation"),
      bullet("Atypical: Chronic cough, laryngitis, hoarseness, asthma, non-cardiac chest pain"),
      bullet("Dysphagia, odynophagia if oesophagitis/stricture develops"),
      head2("Complications"),
      bullet("Oesophagitis (erosive) – graded by Los Angeles Classification (A–D)"),
      bullet("Oesophageal stricture/Barrett's oesophagus – columnar metaplasia, risk of adenocarcinoma"),
      bullet("Barrett's oesophagus → Oesophageal adenocarcinoma"),
      head2("Investigations"),
      bullet("Clinical diagnosis in typical cases"),
      bullet("Upper GI endoscopy: gold standard; assess oesophagitis, Barrett's, biopsy"),
      bullet("24-hour oesophageal pH monitoring / pH-impedance: definitive test for acid exposure"),
      bullet("Oesophageal manometry: exclude achalasia, motility disorders"),
      head2("Management"),
      bullet("Lifestyle: weight reduction (most broadly applicable), avoid refluxogenic foods, elevate head of bed, avoid eating before retiring"),
      bullet("Pharmacological hierarchy: PCABs (Vonoprazan) > PPIs (omeprazole, pantoprazole) > H2RA (famotidine)"),
      bullet("PPIs: heal oesophagitis, relieve symptoms; indefinite therapy common for chronic GERD"),
      bullet("PPI side effects: C. difficile, hypomagnesaemia, B12/iron malabsorption, possible bone fracture risk (controversial)"),
      bullet("Surgical: Laparoscopic Nissen fundoplication – wraps proximal stomach around distal oesophagus; equivalent to PPI for oesophagitis; weigh against dysphagia, bloating, gas-bloat syndrome"),
    ],
    None
))

# ── Q7 ─────────────────────────────────────────────────────────────────────
questions.append((
    7,
    "Causes of malabsorption.",
    "Exam: 2014, 2006",
    [
      head2("Classification of Malabsorption Causes"),
      bullet("Intraluminal phase defects (impaired digestion)"),
      sub_b("Pancreatic exocrine insufficiency: chronic pancreatitis, cystic fibrosis, pancreatic cancer"),
      sub_b("Bile acid deficiency: cholestasis, bacterial overgrowth (deconjugation), ileal disease/resection (interrupted enterohepatic circulation)"),
      sub_b("Zollinger-Ellison syndrome: acid inactivates pancreatic enzymes"),
      bullet("Mucosal phase defects (impaired absorption)"),
      sub_b("Coeliac disease (gluten-sensitive enteropathy) – villous atrophy"),
      sub_b("Tropical sprue – chronic infectious enteropathy"),
      sub_b("Whipple's disease (Tropheryma whipplei)"),
      sub_b("Giardiasis, Cryptosporidiosis"),
      sub_b("Crohn's disease of small intestine"),
      sub_b("Intestinal lymphoma"),
      sub_b("Radiation enteritis"),
      sub_b("Short bowel syndrome (following resection)"),
      sub_b("Abetalipoproteinaemia – impaired chylomicron formation"),
      bullet("Lymphatic/vascular defects"),
      sub_b("Intestinal lymphangiectasia – protein-losing enteropathy"),
      sub_b("Intestinal ischaemia"),
      bullet("Post-surgical causes"),
      sub_b("Gastrectomy (Billroth I/II) – dumping syndrome, blind loop"),
      sub_b("Ileocaecal resection"),
      sub_b("Bariatric surgery"),
      bullet("Enzymatic deficiencies"),
      sub_b("Lactase deficiency – lactose intolerance"),
      sub_b("Sucrase-isomaltase deficiency"),
      head2("Presentation Clues"),
      bullet("Fat malabsorption → Steatorrhoea (bulky, greasy, foul-smelling stools), fat-soluble vitamin deficiency (A, D, E, K)"),
      bullet("Carbohydrate malabsorption → Osmotic diarrhoea, bloating, flatulence"),
      bullet("Protein malabsorption → Hypoalbuminaemia, oedema, muscle wasting"),
    ],
    None
))

# ── Q8 ─────────────────────────────────────────────────────────────────────
questions.append((
    8,
    "Diagnosis, investigations, and management of malabsorption.",
    "Exam: 2013, 2007, 2006",
    [
      head2("Clinical Features Suggesting Malabsorption"),
      bullet("Chronic diarrhoea (steatorrhoea), weight loss, fatigue, abdominal bloating"),
      bullet("Signs of nutritional deficiencies: anaemia, peripheral oedema, glossitis, cheilosis, dermatitis, tetany, night blindness"),
      head2("Investigations"),
      head2("Screening Tests"),
      bullet("FBC: anaemia (iron, B12, or folate deficiency)"),
      bullet("Serum albumin, prealbumin: ↓ in malabsorption"),
      bullet("Serum B12, folate, iron studies, ferritin"),
      bullet("Fat-soluble vitamins: A, D, E, K (PT prolonged with vit K deficiency)"),
      bullet("Serum calcium, magnesium, zinc, phosphate"),
      head2("Tests for Fat Malabsorption"),
      bullet("72-hour faecal fat collection (gold standard): >7 g/day = steatorrhoea"),
      bullet("Sudan III stain on stool: screening for fat globules"),
      head2("Tests for Specific Causes"),
      bullet("Coeliac disease: TTG-IgA (screening test of choice), serum IgA level; confirm with upper GI endoscopy + duodenal biopsy (villous atrophy, crypt hyperplasia, ↑ intraepithelial lymphocytes)"),
      bullet("Pancreatic exocrine insufficiency: faecal elastase-1 (↓), secretin stimulation test, CT/MRI pancreas"),
      bullet("Bacterial overgrowth: hydrogen breath test, duodenal aspirate culture"),
      bullet("Giardia: stool antigen test, duodenal aspirate"),
      bullet("Schilling test: distinguishes B12 malabsorption causes (historical)"),
      head2("Imaging"),
      bullet("CT abdomen: pancreatic disease, lymphadenopathy, thickened bowel loops"),
      bullet("MRI/MRCP: biliary and pancreatic duct pathology"),
      bullet("Small bowel follow-through / MRI enterography: Crohn's, lymphoma"),
      bullet("Capsule endoscopy: small bowel mucosal disease"),
      head2("Management"),
      bullet("Treat underlying cause (e.g., gluten-free diet for coeliac, antibiotics for SIBO, enzyme replacement for EPI)"),
      bullet("Nutritional supplementation: iron, B12 (IM if ileal disease), folate, fat-soluble vitamins (A, D, E, K), calcium, magnesium"),
      bullet("Medium-chain triglycerides (MCT) oil: bypasses lymphatic absorption, useful in lymphangiectasia"),
      bullet("Pancreatic enzyme replacement: 25,000–50,000 units lipase per meal for EPI"),
      bullet("Low-lactose diet if lactase deficiency"),
      bullet("Parenteral nutrition: if severe malabsorption/short bowel syndrome"),
    ],
    None
))

# ── Q9 ─────────────────────────────────────────────────────────────────────
questions.append((
    9,
    "Ulcerative colitis.",
    "Exam: 2024, 2021, 2018, 2015",
    [
      head2("Definition"),
      bullet("Chronic relapsing inflammatory bowel disease affecting the rectum and extending proximally in a continuous fashion"),
      head2("Pathology"),
      bullet("Limited to colon and rectum; always involves rectum (proctitis)"),
      bullet("Continuous mucosal inflammation (no skip lesions)"),
      bullet("Macroscopic: loss of haustrations, granular/friable mucosa, pseudopolyps, ulceration"),
      bullet("Microscopic: crypt architectural distortion, crypt abscesses, goblet cell depletion, mucosal inflammation"),
      head2("Montreal Classification"),
      bullet("E1: Proctitis – limited to rectum"),
      bullet("E2: Left-sided (distal) – to splenic flexure"),
      bullet("E3: Extensive / Pancolitis – proximal to splenic flexure"),
      bullet("Severity: S0 (remission), S1 (mild: ≤4 stools/day), S2 (moderate: ≥4 stools/day, minimal systemic illness), S3 (severe: ≥6 bloody stools/day, HR ≥90, temp ≥37.5°C, Hb <10.5, ESR ≥30)"),
      head2("Clinical Features"),
      bullet("Diarrhoea (often bloody), rectal bleeding, tenesmus, passage of mucus, crampy abdominal pain"),
      bullet("Severity correlates with extent of disease"),
      bullet("Proctitis: fresh blood/mucus, tenesmus, rarely abdominal pain; may have proximal constipation"),
      bullet("Systemic: fever, weight loss, malaise in severe disease"),
      head2("Investigations"),
      bullet("FBC: anaemia, leukocytosis; ESR, CRP elevated in active disease"),
      bullet("Stool culture: exclude infection (Salmonella, Shigella, C. difficile, CMV)"),
      bullet("Colonoscopy + biopsy: diagnostic; assess extent and severity"),
      bullet("AXR: toxic megacolon (transverse colon >6 cm), loss of haustration"),
      head2("Management"),
      bullet("Proctitis/mild-moderate distal UC: Topical aminosalicylates (mesalazine suppositories/enema) ± topical steroids"),
      bullet("Mild-moderate extensive UC: Oral aminosalicylates (mesalazine/sulfasalazine) ± topical therapy"),
      bullet("Moderate-severe: Systemic corticosteroids (prednisolone)"),
      bullet("Steroid-refractory/dependent: Azathioprine, 6-MP; or Biologics: Infliximab, Adalimumab (anti-TNF), Vedolizumab (anti-integrin), Ustekinumab"),
      bullet("Severe colitis (hospitalised): IV hydrocortisone; if no response in 3–5 days → IV ciclosporin or Infliximab; if still failing → colectomy"),
      bullet("Surgery (colectomy): curative for UC; indications: toxic megacolon, perforation, refractory disease, high-grade dysplasia/cancer"),
    ],
    [
        ("https://cdn.orris.care/cdss_images/62fa6f415d16466c366337db8ebac4b02e26312feda4e513e27ff1bb76a5acbd.png",
         "Fig. 337-6 – Crohn's colitis histology (mixed inflammation, granulomas) (Harrison's 22E)")
    ]
))

# ── Q10 ─────────────────────────────────────────────────────────────────────
questions.append((
    10,
    "Celiac disease in adults. OR: List the causes of chronic diarrhea. Describe the clinical features, diagnosis, and treatment of celiac disease in adults.",
    "Exam: 2018 / 2021, 2017, 2016",
    [
      head2("Causes of Chronic Diarrhoea"),
      bullet("Osmotic: osmotic laxatives, lactose intolerance, coeliac disease"),
      bullet("Secretory: VIPoma, carcinoid, bile acid malabsorption, microscopic colitis"),
      bullet("Inflammatory: IBD (UC, CD), infectious (Giardia, CMV), radiation enteritis"),
      bullet("Malabsorptive: coeliac disease, chronic pancreatitis, tropical sprue, Whipple's"),
      bullet("Motility: IBS, hyperthyroidism, post-vagotomy, diabetic autonomic neuropathy"),
      bullet("Structural: diverticular disease, fistula, short bowel syndrome"),
      head2("Celiac Disease – Definition"),
      bullet("Small-intestinal enteropathy caused by immune response to gluten (wheat, rye, barley, some oats); autoantibodies to tissue transglutaminase (TTG)"),
      bullet("Global prevalence 1.4%; 10–15% in first-degree relatives"),
      head2("Genetics"),
      bullet("HLA-DQ2 (95% of patients) and HLA-DQ8; necessary but not sufficient"),
      bullet("Negative HLA-DQ2/DQ8 has >99% negative predictive value for ruling out coeliac disease"),
      head2("Clinical Features"),
      bullet("Classic: Diarrhoea, steatorrhoea, weight loss, growth failure in children"),
      bullet("Atypical: Bloating, iron-deficiency anaemia (duodenal disease), osteoporosis, elevated liver enzymes, migraine, ataxia, dermatitis herpetiformis"),
      bullet("Associated conditions: Type 1 DM, autoimmune thyroid disease, Down syndrome, Turner syndrome"),
      bullet("Dermatitis herpetiformis: vesicular rash, IgA deposits in skin – highly associated with coeliac"),
      head2("Diagnosis"),
      bullet("Serology (screening): TTG-IgA (test of choice) + serum total IgA (to exclude IgA deficiency)"),
      bullet("If IgA deficient: TTG-IgG or anti-deamidated gliadin peptide (DGP-IgG)"),
      bullet("Confirm with upper GI endoscopy + duodenal biopsy (Marsh classification)"),
      bullet("Biopsy shows: villous blunting/atrophy, crypt hyperplasia, increased intraepithelial lymphocytes"),
      head2("Treatment"),
      bullet("Strict lifelong gluten-free diet (GFD) – cornerstone of treatment"),
      bullet("Nutritional supplementation: iron, folate, B12, calcium, vitamin D"),
      bullet("Monitor TTG-IgA titres to assess dietary adherence"),
      bullet("Refractory coeliac disease (not responding to GFD): steroids, azathioprine, biologics"),
      bullet("Screen for complications: T-cell lymphoma (enteropathy-associated), adenocarcinoma of small bowel"),
    ],
    None
))

# ── Q11 ─────────────────────────────────────────────────────────────────────
questions.append((
    11,
    "Ulcerative colitis versus Crohn's disease.",
    "Exam: 2018",
    [
      head2("Comparison Table: UC vs Crohn's Disease"),
      Paragraph("""<para>
      <font size="9">
      <b>Feature</b> / <b>Ulcerative Colitis</b> / <b>Crohn's Disease</b><br/>
      Location: Rectum + colon (always) / Any part of GI tract (mouth to anus)<br/>
      Rectal involvement: Always / Spared in 50%<br/>
      Distribution: Continuous / Skip lesions<br/>
      Ileal involvement: None (backwash ileitis) / Very common (terminal ileum)<br/>
      Depth of inflammation: Mucosal only / Transmural (full thickness)<br/>
      Macroscopic: Granular, friable mucosa, pseudopolyps / Cobblestone appearance, linear ulcers, fissures<br/>
      Microscopic: Crypt abscesses, goblet cell depletion / Granulomas (non-caseating) in 30–60%<br/>
      Strictures: Rare (suspect cancer) / Common (fibrotic)<br/>
      Fistulae/Abscesses: Absent / Common (enterocutaneous, perianal, rectovaginal)<br/>
      Perianal disease: Uncommon / Very common (fissures, fistulae, abscesses)<br/>
      Smoking: Protective / Risk factor<br/>
      Bleeding: Very common (rectal) / Less common<br/>
      Cancer risk: ↑ (colorectal) / ↑ (colorectal + small bowel)<br/>
      Surgery: Curative (colectomy) / Not curative; disease recurs<br/>
      ASCA: Negative / Positive (60–70%)<br/>
      pANCA: Positive (60–70%) / Negative<br/>
      </font>
      </para>""", ParagraphStyle("table_para", fontSize=9, leading=13, fontName="Helvetica")),
      head2("Common Features of IBD"),
      bullet("Both are relapsing-remitting inflammatory bowel diseases"),
      bullet("Extraintestinal manifestations: arthritis, uveitis, erythema nodosum, pyoderma gangrenosum, PSC"),
      bullet("Increased risk of thromboembolic events"),
      bullet("Similar medical management principles (aminosalicylates, steroids, immunomodulators, biologics)"),
    ],
    None
))

# ── Q12 ─────────────────────────────────────────────────────────────────────
questions.append((
    12,
    "Tropical sprue.",
    "Exam: 2006",
    [
      head2("Definition"),
      bullet("Chronic malabsorptive disorder occurring in tropical regions (Caribbean, South/Southeast Asia, parts of Africa), characterised by small intestinal mucosal damage"),
      bullet("Distinct from coeliac disease – not related to gluten"),
      head2("Aetiology"),
      bullet("Believed to be infectious in origin; possibly bacterial overgrowth (Klebsiella pneumoniae, Enterobacter, E. coli)"),
      bullet("Nutritional deficiency (folate and B12) perpetuates mucosal damage"),
      bullet("Risk: travellers and residents in endemic areas"),
      head2("Pathology"),
      bullet("Villous atrophy (partial), crypt hyperplasia, increased intraepithelial lymphocytes – resembles coeliac but less severe"),
      bullet("Affects entire small intestine (vs. coeliac which is predominantly proximal)"),
      head2("Clinical Features"),
      bullet("Acute onset: watery diarrhoea, nausea, anorexia, weight loss"),
      bullet("Chronic phase: steatorrhoea, megaloblastic anaemia (folate/B12 deficiency), glossitis, cheilosis"),
      bullet("Signs of malabsorption: oedema, muscle wasting, peripheral neuropathy"),
      head2("Diagnosis"),
      bullet("Clinical: diarrhoea + malabsorption in a tropical endemic region"),
      bullet("D-xylose absorption test: abnormal (impaired absorption)"),
      bullet("Jejunal biopsy: partial villous atrophy (Marsh I–III)"),
      bullet("Negative TTG-IgA serology (differentiates from coeliac)"),
      bullet("Exclude other causes: Giardia stool antigen, infectious stool cultures"),
      head2("Treatment"),
      bullet("Folic acid (5 mg/day) – key; leads to dramatic improvement"),
      bullet("Vitamin B12 injections – if B12 deficient"),
      bullet("Broad-spectrum antibiotics: Tetracycline (250 mg four times daily × 3–6 months) – most effective; or Co-trimoxazole"),
      bullet("Most patients respond within weeks; cure rates >90% with combined therapy"),
    ],
    None
))

# ── Q13 ─────────────────────────────────────────────────────────────────────
questions.append((
    13,
    "Clinical features, etiology, diagnosis, and management of hematemesis / upper GI bleed.",
    "Exam: 2006",
    [
      head2("Definitions"),
      bullet("Haematemesis: vomiting of blood (bright red or coffee-ground appearance)"),
      bullet("Melaena: tarry black offensive stools from digested blood; source usually above the ligament of Treitz"),
      bullet("Upper GI bleed (UGIB): haemorrhage from oesophagus, stomach, or proximal duodenum"),
      head2("Aetiology"),
      bullet("Peptic ulcer disease (most common ~50%): duodenal > gastric ulcer"),
      bullet("Oesophageal/gastric varices (portal hypertension)"),
      bullet("Mallory-Weiss tear: mucosal tear at gastro-oesophageal junction (post-vomiting)"),
      bullet("Erosive gastritis/oesophagitis"),
      bullet("Gastric cancer, GIST"),
      bullet("Dieulafoy lesion: aberrant submucosal artery"),
      bullet("Aortoenteric fistula (post-aortic surgery – rare but catastrophic)"),
      bullet("Haemobilia, Haemosuccus pancreaticus"),
      head2("Clinical Features"),
      bullet("Haematemesis ± coffee-ground vomiting, melaena"),
      bullet("Hypovolaemic shock: pallor, tachycardia, hypotension, sweating, reduced consciousness"),
      bullet("Epigastric pain, dyspepsia (PUD), alcohol history, liver disease stigmata (varices)"),
      head2("Assessment"),
      bullet("Glasgow-Blatchford Score (GBS): guides need for endoscopic intervention (pre-endoscopy)"),
      bullet("Rockall Score: post-endoscopy risk stratification for rebleeding and mortality"),
      head2("Investigations"),
      bullet("FBC, coagulation (PT/APTT), cross-match/group and save"),
      bullet("U&E: elevated BUN:Cr ratio suggests UGIB"),
      bullet("LFTs, clotting: assess for liver disease/coagulopathy"),
      bullet("Urgent upper GI endoscopy (EGD): within 24h (within 12h if haemodynamically unstable/variceal suspected)"),
      head2("Management"),
      bullet("Resuscitation: 2 large-bore IV lines, crystalloid/colloid, blood transfusion (target Hb 7–9 g/dL – restrictive strategy)"),
      bullet("Reverse coagulopathy: FFP, platelets, Vitamin K if needed"),
      bullet("IV PPI (omeprazole/pantoprazole bolus then infusion) for peptic ulcer bleeding"),
      bullet("Octreotide/Terlipressin (vasopressin analogue) for variceal bleeding"),
      bullet("Prophylactic antibiotics (Ceftriaxone) for variceal bleeding in cirrhosis"),
      bullet("Endoscopic haemostasis: adrenaline injection, clips, thermal coagulation, EVL for varices"),
      bullet("Interventional radiology: transcatheter arterial embolisation (TAE) if endoscopy fails"),
      bullet("Surgery: oversewing of bleeding vessel, partial gastrectomy for refractory PUD bleeding"),
    ],
    None
))

# ── Q14 ─────────────────────────────────────────────────────────────────────
questions.append((
    14,
    "Extraintestinal manifestations of ulcerative colitis.",
    "Exam: 2007",
    [
      head2("Overview"),
      bullet("Up to one-third of IBD patients have at least one extraintestinal manifestation (EIM)"),
      head2("Dermatological"),
      bullet("Erythema nodosum (EN): hot, tender, red nodules on anterior shins; occurs in ~10% UC; correlates with bowel activity"),
      bullet("Pyoderma gangrenosum (PG): ulcerating lesion with violaceous undermined edges; 1–12% UC; may be refractory; responds to IV ciclosporin, infliximab"),
      bullet("Sweet's syndrome: neutrophilic dermatosis"),
      head2("Musculoskeletal"),
      bullet("Peripheral arthritis: asymmetric, migratory, large joints; parallels bowel activity; responds to bowel treatment"),
      bullet("Sacroiliitis: symmetric, hips and spine; independent of bowel activity; treat with NSAIDs, anti-TNF"),
      bullet("Ankylosing spondylitis: gradual progressive spinal involvement; independent of bowel activity"),
      head2("Ocular"),
      bullet("Episcleritis: correlates with bowel activity; treated with topical steroids"),
      bullet("Uveitis: independent of bowel activity; urgent ophthalmology referral needed to prevent blindness"),
      bullet("Scleritis: rare but severe"),
      head2("Hepatobiliary"),
      bullet("Primary sclerosing cholangitis (PSC): most serious; progressive fibrosis of biliary tree; 75% of PSC patients have IBD (mostly UC); risk of cholangiocarcinoma"),
      bullet("Fatty liver (steatosis): most common hepatic EIM"),
      bullet("Pericholangitis, Cirrhosis, Autoimmune hepatitis"),
      head2("Thrombotic / Haematological"),
      bullet("DVT, PE: due to hypercoagulable state (↑ fibrinogen, Factor V, Factor VIII, thrombocytosis)"),
      bullet("Anaemia: iron deficiency (bleeding) or anaemia of chronic disease"),
      head2("Metabolic/Other"),
      bullet("Osteoporosis: steroid-induced; also due to inflammatory cytokines"),
      bullet("Amyloidosis (rare): secondary (AA) amyloidosis"),
      bullet("Nephrolithiasis: oxalate stones (increased oxalate absorption due to fat malabsorption in CD; less common in UC)"),
    ],
    None
))

# ── Q15 ─────────────────────────────────────────────────────────────────────
questions.append((
    15,
    "Chronic pancreatitis.",
    "Exam: 2021",
    [
      head2("Definition"),
      bullet("Irreversible progressive fibro-inflammatory destruction of the pancreas leading to exocrine and endocrine insufficiency"),
      head2("Aetiology (TIGAR-O Classification)"),
      bullet("Toxic-metabolic: alcohol (most common, 70–80%), smoking, hypercalcaemia, hypertriglyceridaemia"),
      bullet("Idiopathic: early-onset (<35 yrs) and late-onset (>35 yrs)"),
      bullet("Genetic: PRSS1 (hereditary pancreatitis), SPINK1, CFTR mutations"),
      bullet("Autoimmune: IgG4-related (Type 1 – diffuse), ICDC (Type 2 – duct-centric)"),
      bullet("Recurrent severe acute pancreatitis"),
      bullet("Obstructive: pancreatic divisum, tumour, stricture"),
      head2("Clinical Features"),
      bullet("Chronic/recurrent epigastric pain: often severe, boring, radiating to back; relieved by leaning forward; worse with eating and alcohol"),
      bullet("Exocrine insufficiency: steatorrhoea, malabsorption, weight loss (occurs when >90% pancreatic function is lost)"),
      bullet("Endocrine insufficiency: Diabetes mellitus (pancreatogenic/Type 3c) – late feature"),
      bullet("Jaundice: due to bile duct stricture from fibrosis or pseudocyst compression"),
      head2("Investigations"),
      bullet("Serum amylase/lipase: often normal in chronic disease (parenchymal burnout)"),
      bullet("Faecal elastase-1: ↓ (<100 μg/g = severe insufficiency)"),
      bullet("Glucose tolerance test: DM"),
      bullet("CT abdomen: pancreatic calcification (pathognomonic), duct dilatation, parenchymal atrophy"),
      bullet("MRCP/EUS: ductal anatomy, stones, strictures"),
      head2("Complications (Table 359-7 Harrison's)"),
      bullet("Chronic pain, exocrine/endocrine insufficiency, pseudocyst, biliary stricture"),
      bullet("Splanchnic venous thrombosis, pancreatic duct stricture, metabolic bone disease"),
      bullet("Malnutrition, micronutrient deficiencies, pancreatic cancer (10× increased risk)"),
      head2("Management"),
      bullet("Pain: analgesics (paracetamol → NSAIDs → opioids); pregabalin shown to reduce pain in RCT"),
      bullet("Enzyme replacement: Pancreatin 25,000–50,000 units lipase per meal; PPI co-administration enhances efficacy"),
      bullet("Diabetes: insulin (oral agents less effective due to reduced glucagon as well)"),
      bullet("Nutritional: fat-soluble vitamins (A, D, E, K), zinc, calcium, periodic bone density monitoring"),
      bullet("Endoscopic: sphincterotomy, stenting, stone extraction, pseudocyst drainage"),
      bullet("Surgical: ductal decompression (Puestow procedure – lateral pancreaticojejunostomy); 80% immediate pain relief; 50% recurrence at 3 years; superior to endoscopy in two RCTs"),
      bullet("Stop alcohol and smoking – essential"),
    ],
    None
))

# ── Q16 ─────────────────────────────────────────────────────────────────────
questions.append((
    16,
    "Zollinger-Ellison syndrome.",
    "Exam: 2021",
    [
      head2("Definition"),
      bullet("Severe peptic ulcer diathesis due to gastric acid hypersecretion from unregulated gastrin release from a non-β-cell neuroendocrine tumour (gastrinoma) of the pancreas or duodenum"),
      head2("Epidemiology"),
      bullet("Rare: 0.5–3 per million population; estimated 0.1–1% of PUD patients"),
      bullet("Mean age: 30–65 years; females slightly more common"),
      bullet("Diagnosis often delayed 4–7 years after symptom onset"),
      bullet("80% sporadic; 20% associated with MEN-1 (Multiple Endocrine Neoplasia type 1)"),
      head2("Pathophysiology"),
      bullet("Gastrinoma → autonomous gastrin secretion → ↑↑ gastric acid (via parietal cell stimulation and ECL cell histamine release)"),
      bullet("Gastrin also has trophic effect on gastric epithelial cells → parietal cell hyperplasia"),
      bullet("Consequence: severe PUD, erosive oesophagitis, diarrhoea"),
      head2("Tumour Location"),
      bullet("Gastrinoma triangle (60–90%): bounded by cystic-CBD junction (superior), D2–D3 junction (inferior), neck/body of pancreas (medial)"),
      bullet("Duodenum (most common extrapancreatic site): smaller, slower growing, less likely to metastasise"),
      bullet(">60% tumours malignant (local invasion/metastasis); 30–50% have metastatic disease at presentation"),
      head2("Clinical Manifestations"),
      bullet("Peptic ulcer (>90%): most common; often severe, refractory, multiple, atypical locations (D2 and beyond)"),
      bullet("Suspect ZES when: ulcers in unusual locations, refractory to standard therapy, recurrence after acid-reducing surgery, ulcers with frank complications (perforation, haemorrhage), associated with diarrhoea"),
      bullet("Diarrhoea (30–40%): due to acid inactivation of enzymes, direct intestinal damage"),
      bullet("GORD/oesophagitis: severe, erosive"),
      head2("Diagnosis"),
      bullet("Fasting serum gastrin (FSG): >1000 pg/mL virtually diagnostic; >10× ULN with gastric pH <2 is diagnostic"),
      bullet("Secretin stimulation test: paradoxical rise in gastrin >200 pg/mL after secretin IV injection (gold standard provocative test)"),
      bullet("Basal acid output (BAO): >15 mEq/h; BAO:MAO ratio >0.6"),
      bullet("Localisation: CT/MRI, EUS (most sensitive for pancreatic tumours), Somatostatin receptor scintigraphy (SRS/OctreoScan), 68Ga-DOTATATE PET"),
      head2("Treatment"),
      bullet("Medical: High-dose PPI (e.g., omeprazole 60–80 mg/day) – controls acid hypersecretion in all patients"),
      bullet("Surgical resection: curative in up to 40% with sporadic ZES; all localised, non-MEN-1 cases should be explored"),
      bullet("MEN-1/ZES: medical management preferred (multifocal disease rarely cured surgically)"),
      bullet("Metastatic disease: Somatostatin analogues (octreotide, lanreotide), chemotherapy, PRRT (peptide receptor radionuclide therapy), hepatic artery embolisation"),
    ],
    None
))

# ── Q17 ─────────────────────────────────────────────────────────────────────
questions.append((
    17,
    "Role of H. pylori in gastroduodenal diseases.",
    "Exam: 2016",
    [
      head2("Microbiology"),
      bullet("Helicobacter pylori: gram-negative, microaerophilic, spiral-shaped bacillus"),
      bullet("Colonises gastric antrum; produces urease (converts urea → ammonia + CO2), which buffers acidic environment"),
      bullet("Transmission: faecal-oral, oral-oral; prevalence higher in developing countries (>70%)"),
      head2("Pathogenic Mechanisms"),
      bullet("Urease → NH3 → disrupts mucus layer, direct epithelial damage"),
      bullet("Vacuolating cytotoxin (VacA): pore-forming toxin, causes epithelial vacuolation and apoptosis"),
      bullet("CagA (cytotoxin-associated gene A): virulence factor; injected via Type IV secretion system; activates oncogenic signalling pathways"),
      bullet("Inflammatory response: ↑ IL-8, IL-1β, TNF-α → mucosal inflammation → ↑ gastrin, ↓ somatostatin → ↑ acid secretion"),
      head2("Associated Diseases"),
      bullet("Peptic ulcer disease: H. pylori in ~95% of DU, ~70% of GU cases"),
      bullet("Gastric adenocarcinoma: Group 1 carcinogen (IARC); CagA+ strains have higher oncogenic potential"),
      bullet("MALT lymphoma (Mucosa-Associated Lymphoid Tissue): H. pylori eradication leads to regression in 70–80% of early-stage cases"),
      bullet("Chronic gastritis (Type B antral gastritis): most common GI disease worldwide"),
      bullet("Non-ulcer dyspepsia (functional dyspepsia): modest benefit from eradication"),
      head2("Diagnosis"),
      bullet("Non-invasive: Urea breath test (UBT) – gold standard for active infection; Stool antigen test (SAT) – equally sensitive/specific; Serology (IgG) – cannot distinguish active from past infection"),
      bullet("Invasive (endoscopic biopsy): Rapid urease test (CLO test), Histology (Giemsa/Warthin-Starry stain), Culture (for antibiotic sensitivity)"),
      bullet("Note: PPIs should be stopped 2 weeks, and antibiotics 4 weeks, before testing to avoid false negatives"),
      head2("Treatment (Eradication)"),
      bullet("First-line (areas of low clarithromycin resistance): Clarithromycin-based triple therapy – PPI + Amoxicillin 1g BD + Clarithromycin 500mg BD × 14 days"),
      bullet("First-line (high clarithromycin resistance or allergy): Bismuth quadruple therapy – PPI + Bismuth subcitrate + Metronidazole + Tetracycline × 14 days"),
      bullet("Confirm eradication: UBT or SAT ≥4 weeks after completing therapy and ≥2 weeks after stopping PPI"),
    ],
    None
))

# ── Q18 ─────────────────────────────────────────────────────────────────────
questions.append((
    18,
    "Inflammatory bowel diseases, their types, clinical features, and management.",
    "Exam: 2025",
    [
      head2("Definition"),
      bullet("Chronic idiopathic inflammatory disorders of the GI tract: Ulcerative Colitis (UC) and Crohn's Disease (CD)"),
      bullet("Aetiology: genetic susceptibility + dysregulated immune response to commensal gut bacteria + environmental triggers"),
      head2("Ulcerative Colitis – Key Features"),
      bullet("Confined to colon/rectum; continuous mucosal inflammation; always involves rectum"),
      bullet("Symptoms: bloody diarrhoea, rectal bleeding, tenesmus, cramping"),
      bullet("Complications: toxic megacolon, CRC, perforation"),
      head2("Crohn's Disease – Key Features"),
      bullet("Any part of GI tract (mouth to anus); transmural inflammation; skip lesions"),
      bullet("Most common: terminal ileum and colon"),
      bullet("Symptoms: abdominal pain (RIF), diarrhoea (usually non-bloody), weight loss, perianal disease (fissures, fistulae, abscesses)"),
      bullet("Complications: strictures, fistulae, abscesses, short bowel syndrome, malabsorption"),
      head2("Investigations for IBD"),
      bullet("Bloods: FBC, CRP, ESR, albumin, LFTs, B12, iron studies, ASCA (CD), pANCA (UC)"),
      bullet("Stool: calprotectin (↑↑ in IBD vs. IBS), culture, C. difficile toxin"),
      bullet("Endoscopy: colonoscopy + ileoscopy + biopsy (diagnostic)"),
      bullet("Imaging: MRI enterography/CT enterography (Crohn's – small bowel assessment)"),
      head2("Medical Management"),
      bullet("Aminosalicylates (5-ASA): Mesalazine – first-line for mild-moderate UC; limited role in CD"),
      bullet("Corticosteroids: Prednisolone, Budesonide – for induction of remission; not for maintenance"),
      bullet("Immunomodulators: Azathioprine, 6-Mercaptopurine – maintenance of remission; thiopurines"),
      bullet("Methotrexate: maintenance in CD"),
      bullet("Biologics (moderate-severe / steroid-dependent/refractory):"),
      sub_b("Anti-TNF: Infliximab (IV), Adalimumab (SC), Certolizumab pegol (CD)"),
      sub_b("Anti-integrins: Vedolizumab (UC and CD) – gut-selective"),
      sub_b("Anti-IL-12/23: Ustekinumab (UC and CD)"),
      sub_b("JAK inhibitors: Tofacitinib, Upadacitinib (UC)"),
      head2("Surgical Management"),
      bullet("UC: Colectomy – curative; ileal pouch-anal anastomosis (IPAA/J-pouch)"),
      bullet("CD: Not curative; resection for strictures, fistulae, refractory disease; bowel-conserving surgery"),
    ],
    None
))


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# ── Questions ───────────────────────────────────────────────────────────────
for (num, qtext, years, answer_items, imgs) in questions:
    elems = question_block(num, qtext, years, answer_items, imgs)
    story.extend(elems)

doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number)
print(f"PDF saved to: {OUTPUT}")
print(f"File size: {os.path.getsize(OUTPUT)/1024:.1f} KB")

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