from reportlab.lib.pagesizes import A4 from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm, mm from reportlab.lib.colors import HexColor, black, white 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.pdfgen import canvas from reportlab.lib import colors OUTPUT = "/home/daytona/workspace/jaundice-pathology/Jaundice_Pathology.pdf" # ── Color palette ────────────────────────────────────────────────────────────── DEEP_BLUE = HexColor("#1A3A5C") MID_BLUE = HexColor("#2D6A9F") LIGHT_BLUE = HexColor("#D6E8F7") ACCENT_GOLD = HexColor("#E8A020") TABLE_HEAD = HexColor("#1A3A5C") TABLE_ALT = HexColor("#EBF4FC") SECTION_BG = HexColor("#F0F7FF") RED_ACCENT = HexColor("#C0392B") GREEN_ACCENT= HexColor("#1E8449") # ── Page numbering canvas ────────────────────────────────────────────────────── def on_page(canvas_obj, doc): canvas_obj.saveState() # Header bar canvas_obj.setFillColor(DEEP_BLUE) canvas_obj.rect(0, A4[1] - 1.2*cm, A4[0], 1.2*cm, fill=1, stroke=0) canvas_obj.setFillColor(white) canvas_obj.setFont("Helvetica-Bold", 9) canvas_obj.drawString(1.5*cm, A4[1] - 0.82*cm, "JAUNDICE — PATHOLOGY") canvas_obj.setFont("Helvetica", 8) canvas_obj.drawRightString(A4[0] - 1.5*cm, A4[1] - 0.82*cm, "Robbins & Kumar | Harrison's | Pathophysiology") # Footer bar canvas_obj.setFillColor(DEEP_BLUE) canvas_obj.rect(0, 0, A4[0], 1.0*cm, fill=1, stroke=0) canvas_obj.setFillColor(white) canvas_obj.setFont("Helvetica", 8) canvas_obj.drawCentredString(A4[0]/2, 0.35*cm, f"Page {doc.page}") canvas_obj.restoreState() # ── Styles ───────────────────────────────────────────────────────────────────── styles = getSampleStyleSheet() title_style = ParagraphStyle("TitleStyle", fontName="Helvetica-Bold", fontSize=28, textColor=white, alignment=TA_CENTER, spaceAfter=0, spaceBefore=0) subtitle_style = ParagraphStyle("SubtitleStyle", fontName="Helvetica", fontSize=13, textColor=HexColor("#D6E8F7"), alignment=TA_CENTER, spaceAfter=0, spaceBefore=4) h1 = ParagraphStyle("H1", fontName="Helvetica-Bold", fontSize=15, textColor=white, backColor=DEEP_BLUE, spaceBefore=14, spaceAfter=6, leftIndent=-12, rightIndent=-12, borderPadding=(6, 12, 6, 12), leading=20) h2 = ParagraphStyle("H2", fontName="Helvetica-Bold", fontSize=12, textColor=DEEP_BLUE, spaceBefore=10, spaceAfter=4, borderPadding=(0,0,2,0), leading=16) h3 = ParagraphStyle("H3", fontName="Helvetica-BoldOblique", fontSize=11, textColor=MID_BLUE, spaceBefore=8, spaceAfter=3, leading=14) body = ParagraphStyle("Body", fontName="Helvetica", fontSize=10, leading=15, spaceAfter=5, alignment=TA_JUSTIFY, textColor=HexColor("#1C1C1C")) bullet = ParagraphStyle("Bullet", fontName="Helvetica", fontSize=10, leading=14, spaceAfter=3, leftIndent=18, bulletIndent=6, alignment=TA_LEFT, textColor=HexColor("#1C1C1C")) highlight_box = ParagraphStyle("HighlightBox", fontName="Helvetica", fontSize=10, leading=14, spaceAfter=4, leftIndent=10, rightIndent=10, backColor=SECTION_BG, borderPadding=(8,8,8,8), alignment=TA_JUSTIFY, textColor=HexColor("#1C1C1C")) key_point = ParagraphStyle("KeyPoint", fontName="Helvetica-Bold", fontSize=10, leading=14, spaceAfter=4, leftIndent=10, rightIndent=10, backColor=HexColor("#FFF3E0"), borderPadding=(8,8,8,8), textColor=HexColor("#7D3C00")) caption = ParagraphStyle("Caption", fontName="Helvetica-Oblique", fontSize=8.5, textColor=HexColor("#555555"), alignment=TA_CENTER, spaceAfter=6) # ── Helper: section header flowable ─────────────────────────────────────────── def sec(text): return [Spacer(1, 0.3*cm), Paragraph(f" {text}", h1), Spacer(1, 0.15*cm)] def subsec(text): return [Spacer(1, 0.15*cm), Paragraph(text, h2), HRFlowable(width="100%", thickness=1, color=MID_BLUE, spaceAfter=4)] def subsubsec(text): return [Paragraph(text, h3)] def para(text): return Paragraph(text, body) def bul(text): return Paragraph(f"• {text}", bullet) def highlight(text): return Paragraph(text, highlight_box) def keypoint(text): return Paragraph(f"KEY POINT: {text}", key_point) def spacer(h=0.2): return Spacer(1, h*cm) # ══════════════════════════════════════════════════════════════════════════════ # BUILD DOCUMENT # ══════════════════════════════════════════════════════════════════════════════ story = [] # ── COVER PAGE ───────────────────────────────────────────────────────────────── cover_data = [[Paragraph("JAUNDICE", title_style)], [Paragraph("Pathophysiology, Classification, Diagnosis & Management", subtitle_style)], [Spacer(1, 0.3*cm)], [Paragraph("Based on Robbins & Kumar Basic Pathology | Harrison's Principles of Internal Medicine 22E", ParagraphStyle("src", fontName="Helvetica", fontSize=9, textColor=HexColor("#AED6F1"), alignment=TA_CENTER))]] cover_table = Table(cover_data, colWidths=[17*cm]) cover_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), DEEP_BLUE), ("ALIGN", (0,0), (-1,-1), "CENTER"), ("TOPPADDING", (0,0), (-1,-1), 14), ("BOTTOMPADDING", (0,0), (-1,-1), 14), ("LEFTPADDING", (0,0), (-1,-1), 20), ("RIGHTPADDING", (0,0), (-1,-1), 20), ("ROUNDEDCORNERS", [8]), ])) story.append(Spacer(1, 3*cm)) story.append(cover_table) story.append(Spacer(1, 1.0*cm)) # Gold accent band accent_table = Table([[""]], colWidths=[17*cm], rowHeights=[0.5*cm]) accent_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), ACCENT_GOLD), ("ROUNDEDCORNERS", [4]), ])) story.append(accent_table) story.append(Spacer(1, 0.5*cm)) # Quick stat boxes stat_data = [ [Paragraph("Normal Bilirubin
0.3 – 1.2 mg/dL", ParagraphStyle("s", fontName="Helvetica", fontSize=10, alignment=TA_CENTER, textColor=DEEP_BLUE)), Paragraph("Jaundice Visible at
> 2 – 2.5 mg/dL", ParagraphStyle("s", fontName="Helvetica", fontSize=10, alignment=TA_CENTER, textColor=DEEP_BLUE)), Paragraph("Severe Disease
Up to 30 – 40 mg/dL", ParagraphStyle("s", fontName="Helvetica", fontSize=10, alignment=TA_CENTER, textColor=DEEP_BLUE)), Paragraph("Neonatal Jaundice
Matures ~2 weeks", ParagraphStyle("s", fontName="Helvetica", fontSize=10, alignment=TA_CENTER, textColor=DEEP_BLUE))] ] stat_table = Table(stat_data, colWidths=[4.1*cm]*4) stat_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,-1), LIGHT_BLUE), ("BOX", (0,0), (-1,-1), 1, MID_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.5, MID_BLUE), ("TOPPADDING", (0,0), (-1,-1), 10), ("BOTTOMPADDING", (0,0), (-1,-1), 10), ("LEFTPADDING", (0,0), (-1,-1), 8), ("RIGHTPADDING", (0,0), (-1,-1), 8), ("ROUNDEDCORNERS", [4]), ])) story.append(stat_table) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 1 – DEFINITION & OVERVIEW # ══════════════════════════════════════════════════════════════════════════════ story += sec("1. DEFINITION AND OVERVIEW") story.append(para( "Jaundice (icterus) is the yellow discoloration of skin, sclerae, and mucous membranes " "caused by accumulation of bilirubin in tissues. It becomes clinically apparent when " "serum bilirubin exceeds 2–2.5 mg/dL. Levels as high as 30–40 mg/dL can occur in " "severe hepatobiliary disease. Jaundice is not a disease itself but a sign of an underlying " "disorder affecting bilirubin production, transport, conjugation, or excretion." )) story.append(keypoint( "Jaundice is visible when serum bilirubin > 2–2.5 mg/dL. Sclerae are the most sensitive " "site because of the high elastin content that binds bilirubin avidly." )) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 2 – BILIRUBIN METABOLISM # ══════════════════════════════════════════════════════════════════════════════ story += sec("2. BILIRUBIN METABOLISM") story.append(para( "Understanding bilirubin metabolism is fundamental to classifying jaundice pathologically." )) story += subsec("2.1 Production") story.append(para( "Bilirubin is the end product of heme catabolism. Approximately 80–85% is derived from " "hemoglobin released during destruction of senescent red blood cells in the reticuloendothelial " "system (spleen, liver, bone marrow). The remaining 15–20% comes from myoglobin, cytochromes, " "and ineffective erythropoiesis." )) story.append(para( "The enzyme heme oxygenase oxidatively cleaves the alpha-methene bridge of the porphyrin " "ring, producing biliverdin, carbon monoxide, and free iron. Biliverdin reductase then " "reduces biliverdin to bilirubin (unconjugated / indirect bilirubin)." )) story += subsec("2.2 Transport in Blood") story.append(para( "Unconjugated bilirubin is virtually insoluble in water due to tight internal hydrogen " "bonding between its propionic acid carboxyl groups and the imino/lactam groups of the opposite " "dipyrrolic half. To circulate in blood it binds non-covalently to albumin. Because it is " "albumin-bound and insoluble, unconjugated bilirubin:" )) story.append(bul("Cannot be filtered by the renal glomerulus")) story.append(bul("Does NOT appear in urine (acholuria)")) story.append(bul("Is not excreted in bile in its unconjugated form")) story.append(spacer(0.15)) story += subsec("2.3 Hepatic Uptake and Conjugation") story.append(para( "At the hepatocyte sinusoidal membrane, unconjugated bilirubin dissociates from albumin " "and is taken up via carrier-mediated transport (specific transporter not fully " "characterized). Inside the hepatocyte, it binds cytosolic proteins (glutathione-S-transferases / " "ligandin), which reduce back-diffusion into blood." )) story.append(para( "In the smooth endoplasmic reticulum, bilirubin UDP-glucuronosyltransferase (UDPGT) " "conjugates bilirubin to glucuronic acid, yielding bilirubin monoglucuronide and " "diglucuronide (conjugated / direct bilirubin). Conjugation disrupts the internal " "hydrogen bonds, making bilirubin water-soluble and non-toxic." )) story += subsec("2.4 Biliary Excretion") story.append(para( "Conjugated bilirubin is actively transported across the canalicular membrane into bile by " "MRP2 (multidrug resistance-associated protein 2). A small fraction is transported " "into sinusoids by MRP3 and recaptured by OATP1B1/1B3 transporters (enterohepatic recycling " "of conjugated bilirubin)." )) story += subsec("2.5 Intestinal Processing and Urobilinogen") story.append(para( "Conjugated bilirubin is not reabsorbed in the proximal bowel due to its hydrophilicity. " "In the distal ileum and colon, bacterial beta-glucuronidases hydrolyze it back to unconjugated " "bilirubin, which is then reduced to a group of colorless compounds called urobilinogens. " "About 80–90% of these are excreted in feces (oxidized to orange urobilins, which give " "stool its color). The remaining 10–20% undergoes enterohepatic cycling:" )) story.append(bul("Re-absorbed from colon, circulated to liver, re-excreted in bile")) story.append(bul("A small fraction (<3 mg/dL) escapes hepatic re-uptake and is excreted in urine")) story.append(spacer(0.2)) # Metabolism summary table story.append(Spacer(1, 0.15*cm)) met_data = [ ["Step", "Process", "Key Enzyme/Protein", "Location"], ["1", "Heme → Biliverdin", "Heme oxygenase", "RES (spleen/liver/marrow)"], ["2", "Biliverdin → Unconjugated Bilirubin", "Biliverdin reductase", "RES"], ["3", "Blood transport", "Albumin (non-covalent)", "Plasma"], ["4", "Hepatocyte uptake", "Carrier-mediated transport", "Hepatocyte sinusoidal membrane"], ["5", "Cytosolic binding", "Ligandin / GST", "Hepatocyte cytoplasm"], ["6", "Conjugation → Bilirubin glucuronide", "UDPGT", "Smooth ER"], ["7", "Biliary excretion", "MRP2", "Canalicular membrane"], ["8", "Gut reduction → Urobilinogen", "Bacterial beta-glucuronidase", "Colon"], ] met_table = Table(met_data, colWidths=[1.0*cm, 5.0*cm, 5.5*cm, 5.5*cm]) met_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, MID_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("ALIGN", (0,0), (-1,-1), "LEFT"), ("VALIGN", (0,0), (-1,-1), "MIDDLE"), ])) story.append(met_table) story.append(Paragraph("Table 1: Steps in normal bilirubin metabolism", caption)) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 3 – CLASSIFICATION # ══════════════════════════════════════════════════════════════════════════════ story += sec("3. CLASSIFICATION OF JAUNDICE") story.append(para( "Jaundice is classified anatomically into three types based on the site of the defect in " "bilirubin metabolism. This classification guides diagnosis and management." )) # Classification overview table story.append(Spacer(1, 0.2*cm)) class_data = [ ["Feature", "Pre-hepatic\n(Hemolytic)", "Hepatic\n(Hepatocellular)", "Post-hepatic\n(Obstructive/Cholestatic)"], ["Primary defect", "Excessive bilirubin production", "Defective uptake, conjugation, or excretion", "Bile duct obstruction"], ["Bilirubin type", "Unconjugated ↑↑", "Both types (↑ conjugated predominates in severe disease)", "Conjugated ↑↑"], ["Urine bilirubin", "Absent (acholuria)", "Present (bilirubinuria)", "Present (dark urine)"], ["Urine urobilinogen", "Increased", "Variable (↑ early; ↓ late in severe disease)", "Absent or very low"], ["Stool color", "Normal or dark", "Pale/light", "Pale/clay-colored"], ["Liver enzymes", "Normal", "AST/ALT markedly ↑", "ALP/GGT markedly ↑"], ["Bilirubin in urine", "No", "Yes (conjugated)", "Yes (conjugated)"], ["Pruritus", "Absent", "Variable", "Prominent (bile salts)"], ["Examples", "Hemolytic anemia, G6PD deficiency, spherocytosis, ineffective erythropoiesis", "Hepatitis, cirrhosis, drug-induced hepatitis, Gilbert, Crigler-Najjar, Dubin-Johnson", "Gallstones, pancreatic head cancer, cholangiocarcinoma, biliary stricture, PSC"], ] class_table = Table(class_data, colWidths=[3.5*cm, 4.5*cm, 4.5*cm, 4.5*cm]) class_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, DEEP_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(class_table) story.append(Paragraph("Table 2: Comparison of the three types of jaundice", caption)) story.append(Spacer(1, 0.3*cm)) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 4 – PRE-HEPATIC JAUNDICE # ══════════════════════════════════════════════════════════════════════════════ story += sec("4. PRE-HEPATIC JAUNDICE (HEMOLYTIC)") story.append(para( "Pre-hepatic jaundice results from excessive production of bilirubin that overwhelms the " "liver's conjugating capacity, or from impaired hepatic uptake/conjugation." )) story += subsec("4.1 Pathophysiology") story.append(para( "In hemolytic disease, accelerated RBC destruction releases large amounts of heme, which is " "catabolized to unconjugated bilirubin. Although the liver upregulates UDPGT, the conjugating " "capacity is exceeded, leading to unconjugated hyperbilirubinemia. The excess unconjugated " "bilirubin drives more urobilinogen production in the gut, resulting in increased urinary and " "fecal urobilinogen." )) story.append(keypoint( "In pre-hepatic jaundice the bilirubin CANNOT be excreted in urine (it is unconjugated and " "albumin-bound) — hence 'acholuric jaundice' despite elevated serum bilirubin." )) story += subsec("4.2 Causes") causes_pre = [ ["Category", "Examples"], ["Inherited hemolytic", "Hereditary spherocytosis, G6PD deficiency, sickle cell disease, thalassemia, pyruvate kinase deficiency"], ["Acquired hemolytic", "Autoimmune hemolytic anemia (warm/cold), microangiopathic HA (TTP, HUS, DIC), malaria, paroxysmal nocturnal hemoglobinuria"], ["Ineffective erythropoiesis", "Iron deficiency, megaloblastic anemia, lead poisoning, thalassemia major"], ["Neonatal", "Physiologic jaundice, hemolytic disease of newborn (Rh/ABO incompatibility), G6PD deficiency"], ["Hereditary disorders of conjugation", "Gilbert syndrome (mild ↓ UDPGT), Crigler-Najjar type I (absent UDPGT — fatal), Crigler-Najjar type II (severely ↓ UDPGT)"], ] causes_pre_table = Table(causes_pre, colWidths=[5*cm, 12*cm]) causes_pre_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), MID_BLUE), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, MID_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(causes_pre_table) story.append(Paragraph("Table 3: Causes of pre-hepatic jaundice", caption)) story += subsec("4.3 Hereditary Hyperbilirubinemias (Detailed)") # Gilbert syndrome story += subsubsec("Gilbert Syndrome") story.append(para( "Common autosomal recessive condition affecting 4–16% of various populations. Caused by a " "mutation in the promoter of the UGT1A1 gene, leading to mildly decreased glucuronosyltransferase " "expression and mildly decreased hepatic conjugation. Manifests as fluctuating mild unconjugated " "hyperbilirubinemia, often precipitated by fasting, stress, or illness. Benign — no morbidity." )) story += subsubsec("Crigler-Najjar Syndrome") story.append(para( "Caused by other mutations in UGT1A1 that result in severe UDPGT deficiency. Type I: " "complete absence of enzyme — fatal in infancy without liver transplantation (phototherapy " "temporarily maintains safe bilirubin levels). Type II (Arias syndrome): severely reduced " "but not absent UDPGT — less severe, responds to phenobarbital." )) story += subsubsec("Dubin-Johnson Syndrome") story.append(para( "Autosomal recessive disorder caused by defect in the MRP2 canalicular transporter, " "impairing hepatocellular excretion of conjugated bilirubin. Results in conjugated " "hyperbilirubinemia. Distinctive gross pathology: dark-pigmented liver (polymerized " "epinephrine metabolites, not bilirubin). Clinically benign." )) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 5 – HEPATIC JAUNDICE # ══════════════════════════════════════════════════════════════════════════════ story += sec("5. HEPATIC (HEPATOCELLULAR) JAUNDICE") story.append(para( "Hepatocellular jaundice results from diffuse damage to hepatocytes, impairing their capacity " "to take up, conjugate, and/or excrete bilirubin. Both conjugated and unconjugated bilirubin " "may accumulate depending on the nature and severity of the injury." )) story += subsec("5.1 Pathophysiology") story.append(para( "Widespread hepatocyte necrosis or dysfunction disrupts one or more steps in bilirubin " "metabolism. Damaged hepatocytes may regurgitate conjugated bilirubin back into sinusoidal " "blood, causing conjugated hyperbilirubinemia and bilirubinuria. Impaired conjugation causes " "unconjugated accumulation. Canalicular damage and intrahepatic cholestasis may coexist. " "Both AST/ALT (hepatocyte damage) and ALP/GGT (cholestatic component) may be elevated." )) story += subsec("5.2 Causes") hep_causes = [ ["Category", "Examples"], ["Viral hepatitis", "Hepatitis A, B, C, D, E; EBV hepatitis; CMV hepatitis"], ["Drug-induced liver injury (DILI)", "Predictable (dose-dependent): acetaminophen, methotrexate\nIdiosyncratic: isoniazid, halothane, statins, many others"], ["Toxic", "Amanita phalloides mushrooms, vinyl chloride, CCl4, kava"], ["Alcoholic liver disease", "Steatohepatitis → fibrosis → cirrhosis"], ["Autoimmune hepatitis", "Anti-smooth muscle Ab, ANA positive; elevated IgG"], ["Metabolic/hereditary", "Wilson's disease (↑ copper), hemochromatosis (↑ iron), alpha-1-antitrypsin deficiency"], ["Cirrhosis (end-stage)", "Any cause; impaired overall hepatocyte function"], ["Ischemic hepatitis", "Shock, cardiac failure, Budd-Chiari syndrome"], ] hep_table = Table(hep_causes, colWidths=[5*cm, 12*cm]) hep_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), MID_BLUE), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, MID_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(hep_table) story.append(Paragraph("Table 4: Causes of hepatocellular jaundice", caption)) story.append(Spacer(1, 0.2*cm)) story += subsec("5.3 Morphology of Hepatocellular Injury") story.append(para( "The morphologic features vary with the causative agent but common patterns include:" )) story.append(bul("Ballooning degeneration: hepatocyte swelling due to inability to maintain ion pumps; " "cytoplasm becomes pale and rarefied")) story.append(bul("Apoptosis (acidophil bodies / Councilman bodies): shrunken, eosinophilic hepatocytes " "with condensed nuclei, seen especially in viral hepatitis")) story.append(bul("Steatosis (fatty change): large or small lipid vacuoles; prominent in alcoholic " "and metabolic liver disease")) story.append(bul("Mallory-Denk bodies: eosinophilic intracytoplasmic inclusions of aggregated " "intermediate filaments (cytokeratin 8/18); classic for alcoholic hepatitis but also in NAFLD, " "Wilson's, primary biliary cirrhosis")) story.append(bul("Necrosis patterns: spotty lobular necrosis (viral), centrilobular (zone 3) " "necrosis (ischemia/drug toxicity), bridging necrosis (severe hepatitis), massive necrosis " "(fulminant hepatic failure)")) story.append(bul("Lobular disarray: loss of normal hepatic plate architecture due to diffuse " "hepatocyte dropout and regeneration")) story.append(Spacer(1, 0.3*cm)) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 6 – POST-HEPATIC JAUNDICE / CHOLESTASIS # ══════════════════════════════════════════════════════════════════════════════ story += sec("6. POST-HEPATIC JAUNDICE (CHOLESTASIS / OBSTRUCTIVE)") story.append(PageBreak()) story.append(para( "Post-hepatic jaundice is caused by obstruction of bile flow at any level from the intrahepatic " "bile canaliculi to the ampulla of Vater. The hallmark is conjugated hyperbilirubinemia " "with elevated alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), " "because these enzymes are located on the apical (canalicular) membrane of hepatocytes and " "cholangiocytes." )) story += subsec("6.1 Pathophysiology of Cholestasis") story.append(highlight( "Cholestasis is defined as impaired bile flow, resulting in accumulation of bile constituents " "(bilirubin, bile salts, cholesterol) in blood and tissues. It may be extrahepatic " "(obstruction of major bile ducts) or intrahepatic (impairment of hepatocyte bile secretion " "or small duct disease). The distinction is clinically critical because extrahepatic obstruction " "is often surgically correctable, while intrahepatic cholestasis is not improved by surgery." )) story.append(para( "Elevated serum bile salts are responsible for the characteristic pruritus of cholestasis. " "Malabsorption of fat-soluble vitamins (A, D, E, K) results from reduced bile entering the gut. " "Vitamin K deficiency leads to a coagulopathy that is reversible with parenteral vitamin K " "(distinguishing it from the coagulopathy of hepatocellular failure, which is not)." )) story += subsec("6.2 Morphology of Cholestasis (Robbins Pathology)") story.append(para( "The morphologic features of cholestasis depend on severity, duration, and cause. " "Characteristic findings include:" )) story.append(bul("Bile pigment accumulation: elongated green-brown plugs of bile in dilated " "bile canaliculi — the most characteristic finding")) story.append(bul("Feathery degeneration of hepatocytes: a fine, foamy cytoplasmic appearance " "as bile accumulates within hepatocytes")) story.append(bul("Kupffer cell bile pigment: rupture of canaliculi leads to extravasation of " "bile, which is rapidly phagocytosed by Kupffer cells")) story.append(bul("Apoptotic hepatocytes: occasional acidophilic bodies may be seen")) story.append(bul("Ductular reaction: proliferation of reactive bile ductules at the " "portal-parenchymal interface in chronic or extrahepatic obstruction")) story.append(bul("Stromal edema and neutrophils: hallmark of superimposed ascending cholangitis")) story.append(Spacer(1, 0.15*cm)) story.append(para( "If obstruction is prolonged and uncorrected, periportal fibrosis develops, eventually producing " "secondary (obstructive) biliary cirrhosis. Periportal hepatocytes show extensive feathery " "degeneration, often with Mallory hyaline bodies, and bile infarcts form from the detergent " "effects of extravasated bile." )) story += subsec("6.3 Causes of Post-Hepatic Jaundice") post_causes = [ ["Level", "Cause"], ["Common bile duct — stones", "Choledocholithiasis (most common cause in adults)"], ["Common bile duct — malignant", "Pancreatic head adenocarcinoma (classic painless jaundice), cholangiocarcinoma, ampullary carcinoma"], ["Common bile duct — benign stricture", "Post-cholecystectomy stricture, post-inflammatory stricture"], ["Biliary tree inflammation", "Primary sclerosing cholangitis (PSC), ascending cholangitis"], ["Pediatric causes", "Biliary atresia (most common surgical cause in neonates), choledochal cyst, Alagille syndrome (paucity of intrahepatic bile ducts), cystic fibrosis"], ["Extrinsic compression", "Lymphoma, metastatic lymph nodes, mirizzi syndrome"], ["Intrahepatic cholestasis", "Drug-induced (chlorpromazine, OCP), intrahepatic cholestasis of pregnancy, PBC, viral hepatitis cholestatic variant"], ] post_table = Table(post_causes, colWidths=[5*cm, 12*cm]) post_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), MID_BLUE), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, MID_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(post_table) story.append(Paragraph("Table 5: Causes of post-hepatic (obstructive) jaundice", caption)) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 7 – NEONATAL JAUNDICE # ══════════════════════════════════════════════════════════════════════════════ story += sec("7. NEONATAL JAUNDICE") story.append(para( "Neonatal jaundice deserves special attention because of its frequency and the risk of " "neurologic damage (kernicterus) from unconjugated bilirubin toxicity in the immature brain." )) story += subsec("7.1 Physiologic Jaundice of the Newborn") story.append(para( "The hepatic machinery for conjugating and excreting bilirubin does not fully mature until " "approximately 2 weeks of age. As a result, nearly every newborn develops transient, " "mild unconjugated hyperbilirubinemia — termed physiologic (neonatal) jaundice. This is " "compounded by:" )) story.append(bul("High rate of fetal RBC destruction (higher hemoglobin turnover at birth)")) story.append(bul("Immature hepatic UDPGT activity")) story.append(bul("Breastfeeding jaundice: bilirubin-deconjugating enzymes present in breast milk " "can exacerbate hyperbilirubinemia (breast milk jaundice)")) story.append(Spacer(0.1, 0.1*cm)) story.append(para( "Treatment: Phototherapy with blue light converts bilirubin to a water-soluble isomer " "that can be excreted in urine without conjugation, maintaining safe levels until hepatic " "maturation. Sustained jaundice beyond 2 weeks in a neonate is abnormal and requires workup." )) story += subsec("7.2 Kernicterus") story.append(highlight( "When serum unconjugated bilirubin exceeds the albumin-binding capacity, free (unbound) " "unconjugated bilirubin crosses the immature blood-brain barrier and is deposited in neurons " "of the basal ganglia, hippocampus, cerebellum, and brainstem nuclei, causing toxic injury. " "This condition — kernicterus (bilirubin encephalopathy) — can lead to cerebral palsy, " "sensorineural hearing loss, gaze palsy, and intellectual disability. It is the major " "complication of hemolytic disease of the newborn (erythroblastosis fetalis) due to " "Rh or ABO incompatibility." )) story += subsec("7.3 Neonatal Cholestasis") story.append(para( "Prolonged conjugated hyperbilirubinemia in the neonate (neonatal cholestasis) affects " "~1 in 2500 live births and is always pathological. Major causes:" )) story.append(bul("Biliary atresia: fibro-inflammatory obliteration of the extrahepatic biliary tree; " "most common surgical cause; presents in first 2–8 weeks; requires Kasai portoenterostomy")) story.append(bul("Neonatal hepatitis: heterogeneous group including alpha-1-antitrypsin deficiency, " "galactosemia, tyrosinemia, PFIC (progressive familial intrahepatic cholestasis), CMV, rubella, " "toxoplasma, syphilis, and idiopathic causes (>10–15% of cases)")) story.append(bul("Alagille syndrome: paucity of intrahepatic bile ducts (bile duct:portal tract ratio " "<0.5); associated with JAG1/NOTCH2 mutations; butterfly vertebrae, peripheral pulmonic stenosis")) story.append(Spacer(1, 0.3*cm)) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 8 – DIAGNOSTIC APPROACH # ══════════════════════════════════════════════════════════════════════════════ story += sec("8. DIAGNOSTIC APPROACH TO JAUNDICE") story += subsec("8.1 History and Physical Examination") history_data = [ ["Finding", "Suggests"], ["History of blood transfusion/IV drug use", "Viral hepatitis (B, C)"], ["Alcohol use disorder", "Alcoholic hepatitis, cirrhosis"], ["Recent medication changes", "Drug-induced liver injury (DILI)"], ["Fever + rigors + RUQ pain + jaundice (Charcot's triad)", "Ascending cholangitis"], ["Painless progressive jaundice in elderly", "Pancreatic head or cholangiocarcinoma"], ["Colicky RUQ pain + jaundice", "Choledocholithiasis"], ["Pruritus without pain", "Intrahepatic cholestasis, PBC, sclerosing cholangitis"], ["Pregnancy", "Intrahepatic cholestasis of pregnancy, HELLP syndrome, acute fatty liver"], ["Family history of jaundice", "Hereditary disorder (Gilbert, Wilson's, hemolytic anemia)"], ] hist_table = Table(history_data, colWidths=[8*cm, 9*cm]) hist_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, DEEP_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(hist_table) story.append(Paragraph("Table 6: Clinically relevant history findings in jaundice", caption)) story += subsec("8.2 Laboratory Investigations") story.append(para( "Initial blood work should include serum bilirubin fractionation (direct/conjugated vs. " "indirect/unconjugated), liver function tests, and a complete blood count." )) lab_data = [ ["Test", "Pre-hepatic", "Hepatocellular", "Cholestatic"], ["Total bilirubin", "↑ (mild–moderate)", "↑↑↑", "↑↑↑"], ["Direct bilirubin", "Normal or minimal ↑", "↑↑ (predominates late)", "↑↑↑"], ["Indirect bilirubin", "↑↑ (predominates)", "↑↑ (early)", "Normal / mild ↑"], ["AST / ALT", "Normal", "↑↑↑ (>1000 U/L in acute viral)", "Normal or mildly ↑"], ["ALP / GGT", "Normal", "Normal or mildly ↑", "↑↑↑ (ALP >3x ULN)"], ["PT/INR", "Normal", "↑ (hepatic failure)", "↑ (corrects with vit K)"], ["Albumin", "Normal", "↓ (chronic disease)", "Normal"], ["CBC", "Anemia ± reticulocytosis, spherocytes", "May be normal", "Normal"], ["Peripheral smear", "Spherocytes, schistocytes, sickle cells", "Normal or hypersplenism changes", "Normal"], ["Urine bilirubin", "Absent", "Present", "Present"], ["Urine urobilinogen", "↑↑", "Variable", "↓ or absent"], ["Haptoglobin", "↓ or absent", "Normal", "Normal"], ["LDH", "↑", "↑ (hepatic necrosis)", "Normal"], ] lab_table = Table(lab_data, colWidths=[3.5*cm, 4.5*cm, 4.5*cm, 4.5*cm]) lab_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, DEEP_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(lab_table) story.append(Paragraph("Table 7: Laboratory differentiation of jaundice types", caption)) story.append(PageBreak()) story += subsec("8.3 Diagnostic Algorithm (Harrison's Framework)") story.append(para( "The following stepwise approach is recommended for evaluating jaundice " "(based on Harrison's Principles of Internal Medicine 22E):" )) algo_steps = [ ("Step 1", "Determine if bilirubin elevation is ISOLATED or associated with other liver test abnormalities"), ("Step 2", "Fractionate bilirubin: is it predominantly UNCONJUGATED or CONJUGATED?"), ("Step 3", "If unconjugated: is there hemolysis (CBC, reticulocytes, haptoglobin, LDH, peripheral smear) or a hereditary conjugation defect (Gilbert, Crigler-Najjar)?"), ("Step 4", "If conjugated + other LFT abnormalities: is the pattern HEPATOCELLULAR (↑AST/ALT) or CHOLESTATIC (↑ALP/GGT)?"), ("Step 5 — Cholestatic", "Perform ULTRASOUND first to detect biliary dilation. Dilation = extrahepatic obstruction; no dilation = intrahepatic cholestasis"), ("Step 6 — Extrahepatic", "Further imaging: CT, MRCP, ERCP (gold standard for choledocholithiasis), EUS, or PTC"), ("Step 7 — Intrahepatic", "Serologic tests: viral hepatitis panel, ANA, ASMA, AMA (for PBC), ceruloplasmin (Wilson's), ferritin/transferrin saturation (hemochromatosis), IgG4 (autoimmune)"), ("Step 8", "Liver biopsy when diagnosis remains uncertain after non-invasive workup"), ] for step, desc in algo_steps: algo_row_data = [[Paragraph(f"{step}", ParagraphStyle("s1", fontName="Helvetica-Bold", fontSize=9, textColor=white)), Paragraph(desc, ParagraphStyle("s2", fontName="Helvetica", fontSize=9, textColor=HexColor("#1C1C1C")))]] bg = DEEP_BLUE if "Step 1" in step or "Step 2" in step else MID_BLUE if "Step 3" in step or "Step 4" in step else HexColor("#4A90D9") algo_row = Table(algo_row_data, colWidths=[3*cm, 14*cm]) algo_row.setStyle(TableStyle([ ("BACKGROUND", (0,0), (0,0), bg), ("BACKGROUND", (1,0), (1,0), SECTION_BG), ("BOX", (0,0), (-1,-1), 0.5, MID_BLUE), ("TOPPADDING", (0,0), (-1,-1), 6), ("BOTTOMPADDING", (0,0), (-1,-1), 6), ("LEFTPADDING", (0,0), (-1,-1), 8), ("VALIGN", (0,0), (-1,-1), "MIDDLE"), ])) story.append(algo_row) story.append(Spacer(1, 0.1*cm)) story.append(Spacer(1, 0.3*cm)) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 9 – IMAGING # ══════════════════════════════════════════════════════════════════════════════ story += sec("9. IMAGING IN JAUNDICE") story.append(para( "Imaging is essential to distinguish extrahepatic from intrahepatic cholestasis and to " "identify the cause and level of obstruction." )) imaging_data = [ ["Modality", "Role", "Key Advantages / Notes"], ["Ultrasound (USG)", "First-line imaging in all jaundiced patients", "Cheap, no radiation, detects biliary dilation with high sensitivity; poor visualization of distal CBD due to bowel gas"], ["CT abdomen", "Second-line; characterize mass, level of obstruction", "Better for pancreatic head, lymph nodes; shows level of obstruction well"], ["MRCP", "Non-invasive cholangiogram; replaced ERCP as initial test in most cases", "Excellent for visualizing bile ducts, stones, strictures, without radiation or contrast injection"], ["ERCP", "Gold standard for choledocholithiasis; also therapeutic", "Allows stone extraction, stent placement; invasive; risk of post-ERCP pancreatitis"], ["EUS", "Detection of distal CBD stones; allows FNA of masses", "Sensitivity comparable to MRCP for CBD obstruction; invasive but lower risk than ERCP"], ["PTC", "When ERCP fails (altered anatomy)", "Allows biliary drainage and stent placement percutaneously"], ["Liver biopsy", "Intrahepatic cholestasis with uncertain diagnosis", "Defines histologic pattern: hepatitis, PBC, PSC, DILI, hereditary disorders"], ] img_table = Table(imaging_data, colWidths=[3.2*cm, 5.5*cm, 8.3*cm]) img_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, DEEP_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(imaging_data and img_table) story.append(Paragraph("Table 8: Imaging modalities in jaundice", caption)) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 10 – COMPLICATIONS # ══════════════════════════════════════════════════════════════════════════════ story += sec("10. COMPLICATIONS OF JAUNDICE") story += subsec("10.1 Complications of Unconjugated Hyperbilirubinemia") story.append(bul("Kernicterus (Bilirubin Encephalopathy): unconjugated bilirubin crosses the " "blood-brain barrier in neonates (and in adults with severely impaired BBB), depositing in " "basal ganglia and brainstem nuclei, causing permanent neurologic damage — cerebral palsy, " "sensorineural deafness, gaze palsies")) story.append(bul("Renal tubular effects: unbound unconjugated bilirubin may be directly toxic " "to renal tubular cells in hemolytic crises")) story += subsec("10.2 Complications of Conjugated Hyperbilirubinemia / Cholestasis") story.append(bul("Pruritus: bile salts deposited in skin cause severe, debilitating itching")) story.append(bul("Fat-soluble vitamin deficiencies: reduced intraluminal bile acids impair " "absorption of vitamins A (night blindness), D (metabolic bone disease / osteoporosis), " "E (neuropathy), and K (coagulopathy)")) story.append(bul("Steatorrhea: malabsorption of dietary fat due to reduced bile acid pool")) story.append(bul("Skin xanthomas: focal deposition of cholesterol in skin from hypercholesterolemia " "(cholesterol excretion impaired)")) story.append(bul("Secondary biliary cirrhosis: prolonged extrahepatic obstruction leads to " "periportal fibrosis → bridging fibrosis → cirrhosis")) story.append(bul("Ascending cholangitis (Charcot's triad / Reynolds pentad): bacterial infection " "of bile (E. coli, Klebsiella, Enterococcus) — fever, RUQ pain, jaundice; if septic shock " "and confusion (Reynolds pentad) → medical emergency")) story.append(bul("Acute renal failure: bile salts can cause renal vasoconstriction and direct " "tubular toxicity (hepatorenal syndrome in cirrhotic patients)")) story.append(Spacer(1, 0.3*cm)) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 11 – TREATMENT OVERVIEW # ══════════════════════════════════════════════════════════════════════════════ story += sec("11. PRINCIPLES OF MANAGEMENT") story.append(para( "Treatment of jaundice is directed at the underlying cause rather than the jaundice itself." )) mgmt_data = [ ["Type of Jaundice", "Management Principles"], ["Hemolytic (pre-hepatic)", "Treat underlying hemolytic disorder; folic acid supplementation; transfusion if severe; exchange transfusion for severe neonatal jaundice; phototherapy for neonatal unconjugated jaundice"], ["Gilbert syndrome", "No treatment needed; reassurance"], ["Crigler-Najjar type I", "Phototherapy 10–12 hr/day; liver transplantation is curative"], ["Crigler-Najjar type II", "Phenobarbital (induces residual UDPGT); phototherapy"], ["Viral hepatitis", "Supportive; antivirals for HBV/HCV; avoid hepatotoxins; liver transplant for fulminant failure"], ["Drug-induced", "Stop offending drug; N-acetylcysteine for acetaminophen toxicity; supportive care"], ["Alcoholic hepatitis", "Alcohol abstinence; steroids (prednisolone) for severe disease (Maddrey Discriminant Function >32); pentoxifylline as alternative"], ["Autoimmune hepatitis", "Prednisolone ± azathioprine"], ["Wilson's disease", "D-penicillamine or trientine; zinc to reduce absorption; liver transplant for fulminant failure"], ["Choledocholithiasis (obstructive)", "ERCP with sphincterotomy and stone extraction; cholecystectomy"], ["Malignant obstruction", "Biliary stenting (ERCP/PTC); surgical resection if operable; palliative drainage"], ["Biliary atresia (neonate)", "Kasai portoenterostomy; liver transplantation"], ["Primary Biliary Cholangitis (PBC)", "Ursodeoxycholic acid (UDCA); obeticholic acid for incomplete responders"], ["Primary Sclerosing Cholangitis (PSC)", "UDCA (controversial); endoscopic dilation of dominant strictures; liver transplantation"], ["Cholestasis — pruritus", "Cholestyramine (bile acid sequestrant), rifampicin, naltrexone, sertraline"], ] mgmt_table = Table(mgmt_data, colWidths=[5*cm, 12*cm]) mgmt_table.setStyle(TableStyle([ ("BACKGROUND", (0,0), (-1,0), TABLE_HEAD), ("TEXTCOLOR", (0,0), (-1,0), white), ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"), ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"), ("BACKGROUND", (0,1), (0,-1), LIGHT_BLUE), ("FONTSIZE", (0,0), (-1,-1), 8.5), ("ROWBACKGROUNDS",(0,1), (-1,-1), [white, TABLE_ALT]), ("BOX", (0,0), (-1,-1), 0.75, DEEP_BLUE), ("INNERGRID", (0,0), (-1,-1), 0.4, HexColor("#AAAAAA")), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 6), ("RIGHTPADDING", (0,0), (-1,-1), 6), ("VALIGN", (0,0), (-1,-1), "TOP"), ])) story.append(mgmt_table) story.append(Paragraph("Table 9: Management principles by type of jaundice", caption)) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # SECTION 12 – QUICK REVISION SUMMARY # ══════════════════════════════════════════════════════════════════════════════ story += sec("12. QUICK REVISION SUMMARY") story.append(Spacer(1, 0.2*cm)) # Mnemonics / key facts key_facts = [ ("Bilirubin Normal", "0.3 – 1.2 mg/dL total; <0.3 mg/dL direct"), ("Jaundice visible", "> 2 – 2.5 mg/dL"), ("Conjugated bilirubin", "Water-soluble, excreted in urine → bilirubinuria → dark urine"), ("Unconjugated bilirubin", "Water-insoluble, albumin-bound, NOT in urine → acholuric jaundice"), ("Pre-hepatic marker", "↑ Indirect bilirubin, ↑ LDH, ↓ haptoglobin, ↑ urobilinogen, normal ALP/ALT"), ("Hepatic marker", "↑↑ AST/ALT ('hepatocellular enzymes'), both fractions elevated"), ("Post-hepatic marker", "↑↑ ALP + GGT + Direct bilirubin; pale stool, dark urine, pruritus"), ("Charcot's triad", "Fever + RUQ pain + Jaundice = Ascending cholangitis"), ("Reynolds pentad", "Charcot's triad + Shock + Confusion = Suppurative cholangitis (emergency)"), ("Painless jaundice", "Pancreatic head malignancy until proven otherwise (Courvoisier's sign)"), ("Kernicterus risk", "Unconjugated bilirubin > albumin-binding capacity → free bilirubin → brain damage"), ("Courvoisier's law", "Painless jaundice + palpable non-tender gallbladder → malignant obstruction"), ("Gilbert syndrome", "Most common hereditary hyperbilirubinemia; ↓ UGT1A1 promoter; benign; exacerbated by fasting"), ("Dubin-Johnson", "Dark liver (pigmented) + conjugated hyperbilirubinemia; ↓ MRP2; benign"), ("Feathery degeneration", "Hepatocyte cytoplasmic swelling with bile pigment in cholestasis — pathognomonic morphology"), ("1st line imaging", "Ultrasound for all patients with jaundice"), ] for term, fact in key_facts: fact_row = Table([[Paragraph(f"{term}", ParagraphStyle("t1", fontName="Helvetica-Bold", fontSize=9, textColor=DEEP_BLUE)), Paragraph(fact, ParagraphStyle("t2", fontName="Helvetica", fontSize=9, textColor=HexColor("#1C1C1C"))) ]], colWidths=[5*cm, 12*cm]) fact_row.setStyle(TableStyle([ ("BACKGROUND", (0,0), (0,0), LIGHT_BLUE), ("BACKGROUND", (1,0), (1,0), white), ("BOX", (0,0), (-1,-1), 0.4, MID_BLUE), ("TOPPADDING", (0,0), (-1,-1), 5), ("BOTTOMPADDING", (0,0), (-1,-1), 5), ("LEFTPADDING", (0,0), (-1,-1), 8), ("VALIGN", (0,0), (-1,-1), "MIDDLE"), ])) story.append(fact_row) story.append(Spacer(1, 0.05*cm)) story.append(PageBreak()) # ══════════════════════════════════════════════════════════════════════════════ # REFERENCES # ══════════════════════════════════════════════════════════════════════════════ story += sec("REFERENCES") refs = [ "Kumar V, Abbas AK, Aster JC. Robbins & Kumar Basic Pathology, 11th Edition. Elsevier; 2023. " "Chapter 14: Liver and Biliary Tract — Pathophysiology of Jaundice, pp. 619–621.", "Loscalzo J, Fauci A, Kasper D, et al. Harrison's Principles of Internal Medicine, 22nd Edition. " "McGraw-Hill; 2025. Chapter 52: Jaundice, Evaluation of the Patient with Jaundice, pp. 364–370.", "Sleisenger MH, Fordtran JS. Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, " "Management. 11th Edition. Elsevier; 2021.", "Yamada T. Yamada's Textbook of Gastroenterology, 7th Edition. Wiley-Blackwell; 2022. " "Chapter: Cholestatic Liver Injury and Hyperbilirubinemia.", "Goldman L, Cooney KA. Goldman-Cecil Medicine, 27th Edition (International Edition). " "Elsevier; 2024.", ] for i, ref in enumerate(refs, 1): story.append(Paragraph(f"{i}. {ref}", ParagraphStyle("ref", fontName="Helvetica", fontSize=9, leading=13, spaceAfter=5, leftIndent=15, firstLineIndent=-15, textColor=HexColor("#1C1C1C")))) # ── BUILD PDF ───────────────────────────────────────────────────────────────── doc = SimpleDocTemplate( OUTPUT, pagesize=A4, topMargin=1.6*cm, bottomMargin=1.4*cm, leftMargin=1.5*cm, rightMargin=1.5*cm, title="Jaundice — Pathology", author="Orris Medical Library", subject="Pathology of Jaundice", ) doc.build(story, onFirstPage=on_page, onLaterPages=on_page) print("PDF generated:", OUTPUT)