from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.util import Inches, Pt
import copy
from io import BytesIO

# ── Color Palette ──────────────────────────────────────────────────────────────
DARK_BLUE   = RGBColor(0x14, 0x3A, 0x6B)   # header / title bg
MED_BLUE    = RGBColor(0x1E, 0x5C, 0x9C)   # section accent
LIGHT_BLUE  = RGBColor(0xD6, 0xE8, 0xF7)   # content bg
ORANGE      = RGBColor(0xE8, 0x7B, 0x1C)   # highlight / bullet accent
WHITE       = RGBColor(0xFF, 0xFF, 0xFF)
DARK_GRAY   = RGBColor(0x23, 0x23, 0x23)
MID_GRAY    = RGBColor(0x60, 0x60, 0x60)
YELLOW_BG   = RGBColor(0xFF, 0xF5, 0xCC)   # key point boxes
GREEN_ACC   = RGBColor(0x1A, 0x7A, 0x4A)

def rgb(r, g, b):
    return RGBColor(r, g, b)

prs = Presentation()
prs.slide_width  = Inches(13.333)
prs.slide_height = Inches(7.5)

blank_layout = prs.slide_layouts[6]

def add_rect(slide, x, y, w, h, fill_rgb, alpha=None):
    shape = slide.shapes.add_shape(1, Inches(x), Inches(y), Inches(w), Inches(h))
    shape.fill.solid()
    shape.fill.fore_color.rgb = fill_rgb
    shape.line.fill.background()
    return shape

def add_text_box(slide, text, x, y, w, h, font_size=18, bold=False,
                  color=DARK_GRAY, align=PP_ALIGN.LEFT, italic=False,
                  wrap=True, anchor=MSO_ANCHOR.TOP):
    tb = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf = tb.text_frame
    tf.word_wrap = wrap
    tf.vertical_anchor = anchor
    tf.margin_left   = Pt(4)
    tf.margin_right  = Pt(4)
    tf.margin_top    = Pt(2)
    tf.margin_bottom = Pt(2)
    p = tf.paragraphs[0]
    p.alignment = align
    run = p.add_run()
    run.text = text
    run.font.name = "Calibri"
    run.font.size = Pt(font_size)
    run.font.bold = bold
    run.font.italic = italic
    run.font.color.rgb = color
    return tb

def add_multiline_textbox(slide, lines, x, y, w, h, font_size=16,
                           color=DARK_GRAY, bold_first=False, bullet_color=ORANGE,
                           line_spacing=1.1):
    """lines: list of (text, bold, indent_level)"""
    from pptx.oxml.ns import qn
    from lxml import etree
    tb = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf = tb.text_frame
    tf.word_wrap = True
    tf.margin_left   = Pt(6)
    tf.margin_right  = Pt(4)
    tf.margin_top    = Pt(2)
    tf.margin_bottom = Pt(2)
    for i, item in enumerate(lines):
        if isinstance(item, str):
            text, bold, indent = item, False, 0
        elif len(item) == 2:
            text, bold = item; indent = 0
        else:
            text, bold, indent = item

        if i == 0:
            p = tf.paragraphs[0]
        else:
            p = tf.add_paragraph()
        p.alignment = PP_ALIGN.LEFT
        # indent
        if indent > 0:
            p.level = indent
        run = p.add_run()
        run.text = text
        run.font.name = "Calibri"
        run.font.size = Pt(font_size)
        run.font.bold = bold
        run.font.color.rgb = color
    return tb

# ═══════════════════════════════════════════════════════════════════════════════
# SLIDE BUILDERS
# ═══════════════════════════════════════════════════════════════════════════════

def title_slide(prs):
    slide = prs.slides.add_slide(blank_layout)
    # full bg
    add_rect(slide, 0, 0, 13.333, 7.5, DARK_BLUE)
    # bottom accent bar
    add_rect(slide, 0, 6.6, 13.333, 0.9, ORANGE)
    # white semi-box
    add_rect(slide, 0.5, 1.2, 12.333, 4.8, rgb(0xFF,0xFF,0xFF))
    # Title
    add_text_box(slide, "Approach to Hepatosplenomegaly in Children",
                 0.7, 1.4, 12.0, 1.6, font_size=34, bold=True,
                 color=DARK_BLUE, align=PP_ALIGN.CENTER)
    # Sub
    add_text_box(slide, "& Jaundice with Hepatosplenomegaly",
                 0.7, 3.0, 12.0, 0.9, font_size=26, bold=True,
                 color=MED_BLUE, align=PP_ALIGN.CENTER)
    add_text_box(slide, "A Comprehensive Pediatric Approach",
                 0.7, 3.85, 12.0, 0.6, font_size=18,
                 color=MID_GRAY, align=PP_ALIGN.CENTER)
    add_text_box(slide, "References: Nelson Textbook of Pediatrics (21st Ed)  |  Scott's Pediatrics",
                 0.5, 6.62, 12.3, 0.7, font_size=13,
                 color=WHITE, align=PP_ALIGN.CENTER)

def section_divider(prs, section_title, subtitle=""):
    slide = prs.slides.add_slide(blank_layout)
    add_rect(slide, 0, 0, 13.333, 7.5, MED_BLUE)
    add_rect(slide, 0, 3.1, 13.333, 0.08, ORANGE)
    add_text_box(slide, section_title, 1.0, 2.2, 11.3, 1.5,
                 font_size=36, bold=True, color=WHITE, align=PP_ALIGN.CENTER)
    if subtitle:
        add_text_box(slide, subtitle, 1.0, 3.7, 11.3, 1.0,
                     font_size=20, color=LIGHT_BLUE, align=PP_ALIGN.CENTER)

def content_slide(prs, title, bullets, two_col=False, col2_bullets=None,
                  note="", font_size=17):
    slide = prs.slides.add_slide(blank_layout)
    # Header bar
    add_rect(slide, 0, 0, 13.333, 1.0, DARK_BLUE)
    add_rect(slide, 0, 1.0, 13.333, 0.06, ORANGE)
    # Content area bg
    add_rect(slide, 0, 1.06, 13.333, 6.44, LIGHT_BLUE)
    # Title
    add_text_box(slide, title, 0.3, 0.1, 12.7, 0.82,
                 font_size=22, bold=True, color=WHITE, align=PP_ALIGN.LEFT,
                 anchor=MSO_ANCHOR.MIDDLE)
    
    if two_col and col2_bullets:
        col_w = 6.1
        # Col 1
        box1 = slide.shapes.add_textbox(Inches(0.35), Inches(1.18), Inches(col_w), Inches(6.1))
        tf1 = box1.text_frame; tf1.word_wrap = True
        tf1.margin_left = Pt(4); tf1.margin_right = Pt(4)
        tf1.margin_top = Pt(2); tf1.margin_bottom = Pt(2)
        for i, blt in enumerate(bullets):
            p = tf1.paragraphs[0] if i == 0 else tf1.add_paragraph()
            p.alignment = PP_ALIGN.LEFT
            txt, bold = (blt, False) if isinstance(blt, str) else (blt[0], blt[1] if len(blt)>1 else False)
            run = p.add_run(); run.text = txt
            run.font.name = "Calibri"; run.font.size = Pt(font_size)
            run.font.bold = bold; run.font.color.rgb = DARK_GRAY
        # divider
        add_rect(slide, 6.67, 1.18, 0.04, 6.0, MED_BLUE)
        # Col 2
        box2 = slide.shapes.add_textbox(Inches(6.85), Inches(1.18), Inches(col_w), Inches(6.1))
        tf2 = box2.text_frame; tf2.word_wrap = True
        tf2.margin_left = Pt(4); tf2.margin_right = Pt(4)
        tf2.margin_top = Pt(2); tf2.margin_bottom = Pt(2)
        for i, blt in enumerate(col2_bullets):
            p = tf2.paragraphs[0] if i == 0 else tf2.add_paragraph()
            p.alignment = PP_ALIGN.LEFT
            txt, bold = (blt, False) if isinstance(blt, str) else (blt[0], blt[1] if len(blt)>1 else False)
            run = p.add_run(); run.text = txt
            run.font.name = "Calibri"; run.font.size = Pt(font_size)
            run.font.bold = bold; run.font.color.rgb = DARK_GRAY
    else:
        box = slide.shapes.add_textbox(Inches(0.35), Inches(1.18), Inches(12.6), Inches(6.0))
        tf = box.text_frame; tf.word_wrap = True
        tf.margin_left = Pt(6); tf.margin_right = Pt(6)
        tf.margin_top = Pt(4); tf.margin_bottom = Pt(2)
        for i, blt in enumerate(bullets):
            p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
            p.alignment = PP_ALIGN.LEFT
            txt, bold = (blt, False) if isinstance(blt, str) else (blt[0], blt[1] if len(blt)>1 else False)
            run = p.add_run(); run.text = txt
            run.font.name = "Calibri"; run.font.size = Pt(font_size)
            run.font.bold = bold; run.font.color.rgb = DARK_GRAY

    if note:
        add_rect(slide, 0.3, 7.05, 12.7, 0.38, YELLOW_BG)
        add_text_box(slide, "📌 " + note, 0.4, 7.08, 12.5, 0.32,
                     font_size=12, color=rgb(0x80, 0x40, 0x00), italic=True)

def ref_slide(prs):
    slide = prs.slides.add_slide(blank_layout)
    add_rect(slide, 0, 0, 13.333, 1.0, DARK_BLUE)
    add_rect(slide, 0, 1.0, 13.333, 0.06, ORANGE)
    add_rect(slide, 0, 1.06, 13.333, 6.44, LIGHT_BLUE)
    add_text_box(slide, "References", 0.3, 0.1, 12.7, 0.82,
                 font_size=22, bold=True, color=WHITE, align=PP_ALIGN.LEFT,
                 anchor=MSO_ANCHOR.MIDDLE)
    refs = [
        ("1. Kliegman RM, St Geme JW, Blum NJ, et al. Nelson Textbook of Pediatrics, 21st Edition.", True),
        ("   Chapters: Hepatomegaly (Ch. 383), Splenomegaly (Ch. 521), Jaundice (Ch. 384),", False),
        ("   Approach to the Child with Hepatosplenomegaly. Elsevier; 2020.", False),
        ("", False),
        ("2. Scott JR, DiSaia PJ. Scott's Pediatrics (Principles and Practice).", True),
        ("   Sections on Hepatobiliary Disorders, Storage Disorders, Tropical Infections.", False),
        ("", False),
        ("3. Red Book 2021: Report of the Committee on Infectious Diseases, AAP.", True),
        ("   Hepatosplenomegaly index entries: American trypanosomiasis, brucellosis, EBV (p. 784, 238, 318).", False),
        ("", False),
        ("4. Moyer V, et al. Screening for Jaundice - American Academy of Pediatrics 2022 Guidelines.", True),
        ("", False),
        ("5. EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol. 2012;56(3):671-685.", True),
        ("", False),
        ("6. Choudhury J, et al. Approach to Hepatosplenomegaly in Children. Indian Pediatrics 2019.", True),
    ]
    box = slide.shapes.add_textbox(Inches(0.5), Inches(1.2), Inches(12.3), Inches(6.0))
    tf = box.text_frame; tf.word_wrap = True
    tf.margin_left = Pt(4); tf.margin_top = Pt(4)
    for i, (txt, bold) in enumerate(refs):
        p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
        run = p.add_run(); run.text = txt
        run.font.name = "Calibri"; run.font.size = Pt(14)
        run.font.bold = bold; run.font.color.rgb = DARK_GRAY

# ═══════════════════════════════════════════════════════════════════════════════
# BUILD ALL SLIDES
# ═══════════════════════════════════════════════════════════════════════════════

# Slide 1 – Title
title_slide(prs)

# Slide 2 – Outline
content_slide(prs, "Presentation Outline",
[
  ("PART A: Approach to Hepatosplenomegaly in Children", True),
  ("  1.  Definition & Normal Limits", False),
  ("  2.  Anatomy & Pathophysiology of Hepatosplenomegaly", False),
  ("  3.  Clinical Assessment – History", False),
  ("  4.  Clinical Assessment – Examination", False),
  ("  5.  Causes: A Systematic Classification", False),
  ("  6.  Infective Causes", False),
  ("  7.  Hematological Causes", False),
  ("  8.  Metabolic & Storage Disorders", False),
  ("  9.  Investigations: Stepwise Approach", False),
  ("  10. Management Approach", False),
  ("", False),
  ("PART B: Jaundice with Hepatosplenomegaly", True),
  ("  11. Definitions & Bilirubin Metabolism", False),
  ("  12. Classification of Jaundice in Children", False),
  ("  13. Differential Diagnosis with Algorithm", False),
  ("  14. Investigations – Targeted Approach", False),
  ("  15. Specific Conditions: Neonatal & Beyond", False),
  ("  16. Management & References", False),
], font_size=15)

# ─── PART A ──────────────────────────────────────────────────────────────────

# Slide 3 – Section divider
section_divider(prs, "PART A", "Approach to Hepatosplenomegaly in Children")

# Slide 4 – Definition & Normal Limits
content_slide(prs, "Definition & Normal Limits of Liver and Spleen",
[
  ("HEPATOMEGALY (Nelson 21e, Ch. 383):", True),
  ("  • Liver span > 3.5 cm (neonate)  |  > 8 cm (10 yr)  |  > 10.5 cm (adult)", False),
  ("  • Lower edge palpable > 2 cm below right costal margin in children < 5 yrs", False),
  ("  • Normal liver dullness: 6–8 cm in infants; up to 12 cm in older children", False),
  ("", False),
  ("SPLENOMEGALY:", True),
  ("  • Spleen normally NOT palpable after first few weeks of life", False),
  ("  • Palpable spleen tip: mild splenomegaly; > 3 cm below LCM: significant", False),
  ("  • Causes splenic notch palpable on inspiration", False),
  ("", False),
  ("HEPATOSPLENOMEGALY (HSM):", True),
  ("  • Simultaneous enlargement of both liver and spleen", False),
  ("  • Suggests systemic disease – infections, storage disorders, hematological, metabolic", False),
  ("  • Always pathological beyond the neonatal period", False),
],
note="Measurement by percussion + palpation; confirm with USG abdomen. (Nelson 21e, p. 1978)")

# Slide 5 – Anatomy & Pathophysiology
content_slide(prs, "Anatomy & Pathophysiology of Hepatosplenomegaly",
[
  ("WHY LIVER AND SPLEEN ENLARGE TOGETHER?", True),
  ("  • Both are reticuloendothelial system (RES) organs – share mononuclear phagocyte system", False),
  ("  • Portal hypertension: congestion of both organs via portal-splenic axis", False),
  ("  • Systemic infections: immune activation → Kupffer cell hypertrophy, splenic follicular hyperplasia", False),
  ("  • Storage disorders: substrate accumulation in hepatocytes AND splenic macrophages", False),
  ("  • Hematological: extramedullary hematopoiesis in both organs", False),
  ("", False),
  ("MECHANISMS (Scott's Pediatrics):", True),
  ("  1. Inflammation / infection (hepatitis, EBV, CMV, malaria, typhoid, brucellosis)", False),
  ("  2. Venous congestion (portal hypertension, cardiac failure, Budd-Chiari)", False),
  ("  3. Infiltration (leukemia, lymphoma, storage disorders, amyloid)", False),
  ("  4. Extramedullary hematopoiesis (thalassemia, myelofibrosis)", False),
  ("  5. Metabolic overload (Gaucher, Niemann-Pick, glycogen storage)", False),
],
note="Key question: Is hepatomegaly primary with reactive splenomegaly, or splenomegaly primary with portal hypertension?")

# Slide 6 – History Taking
content_slide(prs, "Clinical Assessment – History (Age-Focused Approach)",
two_col=True,
bullets=[
  ("NEONATAL / INFANT (<1 yr)", True),
  ("  • Maternal infections (TORCH – toxoplasma, rubella, CMV, HSV, syphilis)", False),
  ("  • Jaundice onset, duration, colour of stools/urine", False),
  ("  • Feeding difficulty, FTT, developmental delay", False),
  ("  • Family h/o storage disorders, hemolytic anemias", False),
  ("  • Consanguinity → metabolic/storage disorders", False),
  ("", False),
  ("CHILD (1–12 yr)", True),
  ("  • Travel history (malaria, kala-azar, schistosomiasis)", False),
  ("  • Contact: TB, viral hepatitis", False),
  ("  • Fever pattern: remittent (malaria), prolonged (typhoid, kala-azar)", False),
  ("  • Blood transfusions → hemolytic anemia, thalassemia", False),
  ("  • Drug history (isoniazid, valproate, methotrexate → hepatotoxicity)", False),
],
col2_bullets=[
  ("KEY HISTORY POINTS TO ASK:", True),
  ("  • Duration of swelling – acute vs. chronic", False),
  ("  • Pain: hepatic tenderness → acute hepatitis / abscess", False),
  ("  • Colour of stools: pale/acholic → biliary obstruction", False),
  ("  • Colour of urine: dark → conjugated hyperbilirubinemia", False),
  ("  • Weight loss, pallor, bruising → malignancy / hematological", False),
  ("  • Bone pains → leukemia, Gaucher's disease", False),
  ("  • Seizures, neurodegeneration → storage disorders", False),
  ("  • Arthritis, rash → SLE, JIA, viral illness", False),
  ("", False),
  ("NUTRITIONAL STATUS:", True),
  ("  • Kwashiorkor → fatty liver, hepatomegaly", False),
  ("  • Chronic malnutrition + tropical area → kala-azar", False),
],
note="A detailed history often narrows the differential significantly before investigations. (Nelson 21e, Ch. 383)")

# Slide 7 – Examination
content_slide(prs, "Clinical Examination – Systematic Approach",
two_col=True,
bullets=[
  ("GENERAL EXAMINATION:", True),
  ("  • Pallor → hemolysis, malignancy, kala-azar", False),
  ("  • Jaundice → hepatitis, hemolysis, biliary atresia", False),
  ("  • Lymphadenopathy → infectious mononucleosis, lymphoma, TB", False),
  ("  • Petechiae, purpura → leukemia, dengue, ITP", False),
  ("  • Kayser-Fleischer rings → Wilson's disease (slit lamp)", False),
  ("  • Xanthomas → cholestatic liver disease", False),
  ("  • Rash: malar rash → SLE; heliotrope → dermatomyositis", False),
  ("", False),
  ("LIVER EXAMINATION:", True),
  ("  • Size (cm below RCM), surface (smooth/nodular)", False),
  ("  • Consistency: soft (acute), firm (chronic/fibrosis), hard (malignancy)", False),
  ("  • Tenderness: hepatitis, abscess, RHF", False),
  ("  • Hepatic bruit → AVM, hepatocellular carcinoma", False),
],
col2_bullets=[
  ("SPLEEN EXAMINATION:", True),
  ("  • Size (cm below LCM), ballotability", False),
  ("  • Grading: Grade I (<5 cm), II (5–10), III (10–15), IV (>15 cm)", False),
  ("  • Massive splenomegaly → kala-azar, malaria, thalassemia", False),
  ("  • Splenic rub → infarct (sickle cell, SBE)", False),
  ("", False),
  ("SIGNS OF PORTAL HYPERTENSION:", True),
  ("  • Dilated abdominal veins (caput medusae)", False),
  ("  • Ascites → shifting dullness, fluid thrill", False),
  ("  • Splenomegaly + variceal bleeding", False),
  ("", False),
  ("CARDIOVASCULAR:", True),
  ("  • Raised JVP, hepatojugular reflux → CCF", False),
  ("  • Murmur → endocarditis, cyanotic CHD", False),
  ("", False),
  ("NEUROLOGICAL:", True),
  ("  • Flapping tremor → hepatic encephalopathy", False),
  ("  • Regression → storage disorders", False),
],
note="Always examine for signs of chronic liver disease: spider angiomata, palmar erythema, clubbing, leukonychia.")

# Slide 8 – Section: Causes Classification
content_slide(prs, "Causes of Hepatosplenomegaly – Systematic Classification (Nelson 21e)",
two_col=True,
bullets=[
  ("INFECTIONS (Most Common in India):", True),
  ("  • Bacterial: Typhoid, TB, Brucellosis, septicemia", False),
  ("  • Viral: Viral hepatitis (A,B,C,E), EBV, CMV, HIV", False),
  ("  • Parasitic: Malaria, Kala-azar (VL), Toxoplasmosis", False),
  ("  • Helminthic: Schistosomiasis, hydatid (hepatic)", False),
  ("", False),
  ("HEMATOLOGICAL:", True),
  ("  • Hemolytic anemias: Thalassemia major, sickle cell disease", False),
  ("  • Leukemias: ALL (most common pediatric leukemia), AML", False),
  ("  • Lymphomas: Hodgkin's, Non-Hodgkin's", False),
  ("  • Hemophagocytic lymphohistiocytosis (HLH)", False),
  ("  • Hereditary spherocytosis, G6PD deficiency", False),
  ("", False),
  ("METABOLIC / STORAGE:", True),
  ("  • Gaucher's disease (glucocerebrosidase deficiency)", False),
  ("  • Niemann-Pick disease", False),
  ("  • Glycogen storage diseases (esp. type I, III)", False),
  ("  • Mucopolysaccharidoses (Hurler, Hunter)", False),
],
col2_bullets=[
  ("HEPATIC / PORTAL CAUSES:", True),
  ("  • Cirrhosis: biliary atresia, Wilson's, autoimmune hepatitis", False),
  ("  • Portal hypertension: extrahepatic PVT, intrahepatic", False),
  ("  • Budd-Chiari syndrome", False),
  ("  • Congenital hepatic fibrosis", False),
  ("  • Choledochal cyst", False),
  ("", False),
  ("CARDIAC:", True),
  ("  • Congestive cardiac failure (CCF)", False),
  ("  • Pericardial effusion / constrictive pericarditis", False),
  ("  • Cyanotic CHD with RHF", False),
  ("", False),
  ("AUTOIMMUNE:", True),
  ("  • SLE (systemic lupus erythematosus)", False),
  ("  • Juvenile idiopathic arthritis (systemic JIA)", False),
  ("  • Autoimmune hepatitis", False),
  ("", False),
  ("OTHERS:", True),
  ("  • Nutritional: kwashiorkor (fatty liver)", False),
  ("  • Drugs/toxins: hepatotoxicity", False),
  ("  • Neoplastic: neuroblastoma, hepatoblastoma, Wilms' tumor", False),
],
note="In tropical settings, infections are the most common cause. In non-tropical regions, consider hematological and metabolic causes first.")

# Slide 9 – Infective Causes
content_slide(prs, "Infective Causes of Hepatosplenomegaly in Children (Red Book 2021)",
two_col=True,
bullets=[
  ("VIRAL INFECTIONS:", True),
  ("  • EBV (Infectious Mononucleosis):", False),
  ("    – HSM + fever + exudative tonsillitis + lymphadenopathy", False),
  ("    – Monospot test, EBV IgM, Atypical lymphocytes in blood smear", False),
  ("  • CMV: heterophil-negative mono syndrome", False),
  ("  • Viral hepatitis A, B, C, E: transaminitis + HSM", False),
  ("  • HIV: disseminated infection with HSM, FTT, lymphadenopathy", False),
  ("  • Dengue: hepatitis, thrombocytopenia, HSM", False),
  ("", False),
  ("BACTERIAL INFECTIONS:", True),
  ("  • Typhoid (Salmonella typhi): relative bradycardia, rose spots, HSM", False),
  ("  • Brucellosis: undulant fever, arthritis, HSM (Red Book, p. 238)", False),
  ("  • TB: disseminated TB – miliary pattern, hepatic TB", False),
  ("  • Leptospirosis: Weil's disease – jaundice + HSM + AKI", False),
],
col2_bullets=[
  ("PARASITIC INFECTIONS:", True),
  ("  • Malaria (Plasmodium falciparum / vivax):", False),
  ("    – Most common cause of massive splenomegaly", False),
  ("    – Anemia + thrombocytopenia + HSM + fever spikes", False),
  ("    – Thick/thin smear, RDT, PCR", False),
  ("  • Kala-azar (Visceral Leishmaniasis):", False),
  ("    – Classic triad: prolonged fever + progressive massive splenomegaly + wasting", False),
  ("    – Pancytopenia + high serum globulins + rK39 antigen", False),
  ("    – Endemic in Bihar, Jharkhand, Bangladesh (India)", False),
  ("  • Toxoplasmosis: congenital – chorioretinitis + intracranial calcification + HSM", False),
  ("  • TORCH infections (neonatal): CMV, rubella, HSV, syphilis, toxoplasma", False),
  ("  • Schistosomiasis: hepatosplenic form – periportal fibrosis, portal HTN", False),
  ("  • American trypanosomiasis (Red Book, p. 784): cardiac + HSM", False),
],
note="Kala-azar (VL) must be excluded in any child with prolonged fever and massive splenomegaly from endemic areas.")

# Slide 10 – Hematological Causes
content_slide(prs, "Hematological Causes of HSM in Children",
[
  ("HEMOLYTIC ANEMIAS – Chronic hemolysis → extramedullary hematopoiesis (Nelson 21e, Ch. 488):", True),
  ("  • Thalassemia Major (β-thal): Massive HSM, severe pallor, frontal bossing, mongoloid facies", False),
  ("    – Target cells, hypochromia; Hb electrophoresis: HbF ↑, HbA2 ↑; requires transfusions", False),
  ("  • Sickle Cell Disease: Autosplenectomy after repeated infarcts; initial HSM → eventual fibrosis", False),
  ("  • Hereditary Spherocytosis: Moderate HSM, jaundice, cholelithiasis, MCHC ↑, osmotic fragility ↑", False),
  ("  • G6PD deficiency: Episodic hemolysis triggered by infections, drugs, fava beans", False),
  ("", False),
  ("MALIGNANCIES (Nelson 21e, Ch. 523-529):", True),
  ("  • Acute Lymphoblastic Leukemia (ALL): Most common childhood malignancy", False),
  ("    – Bone pains, pallor, petechiae, lymphadenopathy + HSM", False),
  ("    – Blast cells on blood smear; bone marrow biopsy diagnostic", False),
  ("  • AML: Similar but with myeloid characteristics; gum hypertrophy (M5), chloroma", False),
  ("  • Hodgkin's Lymphoma: Reed-Sternberg cells; painless cervical LN; B symptoms", False),
  ("  • Non-Hodgkin's Lymphoma: Burkitt's lymphoma – jaw/abdomen; HSM + ascites", False),
  ("", False),
  ("HLH (Hemophagocytic Lymphohistiocytosis):", True),
  ("  • HScore criteria: Fever + HSM + cytopenias + hyperferritinemia + hypofibrinogenemia + hemophagocytosis on BM", False),
  ("  • Ferritin >10,000 μg/L strongly suggests HLH (Nelson 21e)", False),
],
font_size=15, note="HLH is life-threatening and requires urgent diagnosis and treatment with etoposide + dexamethasone.")

# Slide 11 – Metabolic & Storage
content_slide(prs, "Metabolic & Storage Disorders Causing HSM (Scott's Pediatrics)",
two_col=True,
bullets=[
  ("GAUCHER'S DISEASE:", True),
  ("  • Most common lysosomal storage disorder", False),
  ("  • Deficiency: glucocerebrosidase (GBA gene)", False),
  ("  • Type 1 (non-neuronopathic): Massive splenomegaly > hepatomegaly", False),
  ("  • Type 2: Acute neuronopathic – infantile", False),
  ("  • Type 3: Chronic neuronopathic", False),
  ("  • Blood: pancytopenia; 'Gaucher cells' on BM biopsy", False),
  ("  • Rx: Enzyme replacement therapy (ERT) – imiglucerase", False),
  ("", False),
  ("NIEMANN-PICK DISEASE:", True),
  ("  • Type A/B: Sphingomyelinase deficiency", False),
  ("  • HSM + foam cells ('sea-blue histiocytes') on BM biopsy", False),
  ("  • Type A: Cherry-red spot + neuroregression in infancy", False),
  ("", False),
  ("GLYCOGEN STORAGE DISEASE:", True),
  ("  • GSD Type I (von Gierke): Massive hepatomegaly, hypoglycemia, lactic acidosis", False),
  ("  • GSD Type III: HSM + myopathy + cardiomyopathy", False),
],
col2_bullets=[
  ("MUCOPOLYSACCHARIDOSES:", True),
  ("  • Hurler (MPS I): gargoyle facies, corneal clouding, HSM, developmental delay", False),
  ("  • Hunter (MPS II): X-linked, similar features without corneal clouding", False),
  ("  • Bone marrow transplant in selected cases", False),
  ("", False),
  ("WILSON'S DISEASE:", True),
  ("  • AR, ATP7B gene – copper accumulation", False),
  ("  • HSM + Kayser-Fleischer rings + neuropsychiatric symptoms", False),
  ("  • Low ceruloplasmin (<20 mg/dL), ↑ 24h urine copper, liver biopsy", False),
  ("  • Treatment: D-penicillamine, zinc, liver transplant", False),
  ("", False),
  ("OTHER METABOLIC:", True),
  ("  • α1-antitrypsin deficiency: neonatal cholestasis → cirrhosis", False),
  ("  • Tyrosinemia type I: liver failure, hepatomegaly, coagulopathy", False),
  ("  • Organic acidemias, urea cycle defects: early onset, severe illness", False),
  ("  • Cystic fibrosis: hepatic steatosis → biliary cirrhosis", False),
  ("", False),
  ("CLUE TO STORAGE DISORDER:", True),
  ("  • Consanguinity + coarse facies + skeletal changes + cherry red spot", False),
  ("  • Firm to hard organomegaly + neurodegeneration", False),
],
note="Lysosomal enzyme assay in leukocytes / fibroblasts is definitive. Genetic testing (NGS panel) available.")

# Slide 12 – Investigations Stepwise
content_slide(prs, "Investigations – Stepwise Approach to HSM (Nelson 21e)",
two_col=True,
bullets=[
  ("FIRST-LINE INVESTIGATIONS:", True),
  ("  CBC with differential:", False),
  ("    – Pancytopenia → leukemia, HLH, kala-azar, hypersplenism", False),
  ("    – Eosinophilia → helminthic infections, drugs", False),
  ("    – Atypical lymphocytes → EBV, CMV", False),
  ("    – Hypochromic microcytic + target cells → thalassemia", False),
  ("  Peripheral blood smear:", False),
  ("    – Blast cells, malarial parasites, target cells, spherocytes", False),
  ("  Liver function tests (LFT):", False),
  ("    – ALT/AST ↑ → hepatocellular damage", False),
  ("    – ALP, GGT ↑ → cholestatic/biliary pathology", False),
  ("    – Bilirubin (direct vs indirect)", False),
  ("    – Albumin, PT/INR → synthetic function", False),
  ("  Renal function tests (RFT), electrolytes", False),
  ("  Urine: bile salts, bile pigments, urobilinogen", False),
],
col2_bullets=[
  ("SECOND-LINE INVESTIGATIONS:", True),
  ("  Imaging:", False),
  ("    – USG abdomen: organ size, echogenicity, portal vein diameter, ascites", False),
  ("    – CECT abdomen: lymphadenopathy, masses, portal hypertension", False),
  ("    – Chest X-ray: cardiomegaly, mediastinal widening", False),
  ("  Serology/Specific Tests:", False),
  ("    – Widal test (typhoid), blood culture", False),
  ("    – EBV IgM/monospot, CMV IgM", False),
  ("    – Malarial antigen (RDT), smear, PCR", False),
  ("    – rK39 antigen (kala-azar), splenic aspirate", False),
  ("    – Hepatitis B sAg, Anti-HCV, HAV IgM", False),
  ("    – ANA, anti-dsDNA (SLE), ANCA", False),
  ("  THIRD-LINE:", True),
  ("    – Bone marrow biopsy: leukemia, HLH, storage cells, kala-azar", False),
  ("    – Liver biopsy: cirrhosis staging, storage disorders", False),
  ("    – Lysosomal enzyme assay: storage disorders", False),
  ("    – Ceruloplasmin, 24h urine Cu (Wilson's)", False),
  ("    – Echocardiography: cardiac HSM", False),
],
note="USG abdomen is the single most useful initial investigation to characterize organomegaly and guide further workup.")

# Slide 13 – Algorithm for HSM
content_slide(prs, "Diagnostic Algorithm – Approach to Hepatosplenomegaly in Children",
[
  ("STEP 1: Confirm HSM clinically and with USG abdomen", True),
  ("", False),
  ("STEP 2: CBC + Peripheral smear → Clue to systemic disease", True),
  ("  ➤ Pancytopenia + fever → Kala-azar, HLH, leukemia, severe malaria", False),
  ("  ➤ Hemolytic anemia + HSM → Thalassemia, sickle cell, spherocytosis", False),
  ("  ➤ Blast cells → Leukemia (ALL/AML) → Bone marrow biopsy", False),
  ("", False),
  ("STEP 3: Assess liver function and character of jaundice (if present)", True),
  ("  ➤ Conjugated hyperbilirubinemia → biliary, hepatocellular, metabolic", False),
  ("  ➤ Unconjugated → hemolysis, Gilbert's, Crigler-Najjar", False),
  ("", False),
  ("STEP 4: Signs of portal hypertension?", True),
  ("  ➤ YES → USG Doppler portal vein, endoscopy for varices, liver biopsy", False),
  ("  ➤ NO → continue with infection/metabolic workup", False),
  ("", False),
  ("STEP 5: Consider geographic / travel history", True),
  ("  ➤ Tropical: malaria smear, RDT; kala-azar rK39; typhoid blood culture", False),
  ("  ➤ Non-tropical: Storage disorder screen, autoimmune panel, echocardiography", False),
  ("", False),
  ("STEP 6: Targeted advanced testing based on above clues", True),
  ("  ➤ Bone marrow biopsy, liver biopsy, enzyme assay, genetic testing, cardiac echo", False),
],
font_size=16, note="Clinical context + CBC + USG abdomen form the diagnostic triad for HSM workup.")

# Slide 14 – Management
content_slide(prs, "Management of Hepatosplenomegaly – Cause-Directed Approach",
two_col=True,
bullets=[
  ("INFECTIVE CAUSES:", True),
  ("  • Malaria: Artemisinin-based combination therapy (ACT)", False),
  ("    – Severe malaria: IV Artesunate", False),
  ("  • Kala-azar (VL): Liposomal Amphotericin B (first line India)", False),
  ("    – Miltefosine (oral) for uncomplicated cases", False),
  ("  • Typhoid: Ceftriaxone / Azithromycin", False),
  ("  • Brucellosis: Doxycycline + Rifampicin (6 weeks)", False),
  ("  • EBV: Supportive; avoid contact sports (splenic rupture risk)", False),
  ("  • TB: Anti-TB therapy (HRZE – 2 months + HR 4 months)", False),
  ("", False),
  ("HEMATOLOGICAL:", True),
  ("  • Thalassemia: Regular transfusions + chelation (desferrioxamine/deferasirox)", False),
  ("  • ALL: BFM/COG induction protocol (steroids + vincristine + asparaginase)", False),
  ("  • HLH: HLH-2004 protocol (etoposide + dexamethasone + cyclosporine)", False),
  ("  • Gaucher's Type 1: ERT (imiglucerase/velaglucerase)", False),
],
col2_bullets=[
  ("PORTAL HYPERTENSION:", True),
  ("  • β-blockers (propranolol) for variceal prophylaxis", False),
  ("  • Endoscopic variceal ligation/sclerotherapy", False),
  ("  • TIPS in refractory cases", False),
  ("  • Definitive: Liver transplantation in end-stage disease", False),
  ("", False),
  ("SURGICAL:", True),
  ("  • Splenectomy: Hereditary spherocytosis, massive hypersplenism", False),
  ("    – Risk: Post-splenectomy sepsis → vaccinate (pneumococcus, meningococcus, Hib)", False),
  ("  • Biliary atresia: Kasai portoenterostomy (within 60 days of life)", False),
  ("  • Choledochal cyst: Excision + Roux-en-Y hepaticojejunostomy", False),
  ("", False),
  ("METABOLIC/GENETIC:", True),
  ("  • Enzyme replacement therapy (ERT): Gaucher, Fabry, Pompe", False),
  ("  • Substrate reduction therapy (SRT): miglustat", False),
  ("  • Liver transplant: Tyrosinemia, Wilson's (decompensated), biliary atresia", False),
  ("  • Bone marrow transplant: MPS (selected cases), Gaucher type 3", False),
  ("", False),
  ("SUPPORTIVE:", True),
  ("  • Nutritional support: high-calorie diet, fat-soluble vitamin supplementation", False),
  ("  • Avoid hepatotoxic drugs; careful medication review", False),
],
note="Always address underlying cause; symptomatic management alone is insufficient for HSM.")

# ─── PART B ──────────────────────────────────────────────────────────────────

# Slide 15 – Section divider
section_divider(prs, "PART B", "Jaundice with Hepatosplenomegaly in Children")

# Slide 16 – Bilirubin Metabolism
content_slide(prs, "Bilirubin Metabolism – Normal Pathway (Nelson 21e, Ch. 384)",
[
  ("BILIRUBIN PRODUCTION:", True),
  ("  • Heme catabolism (80–85%): RBC breakdown → heme → biliverdin → unconjugated bilirubin (UCB)", False),
  ("  • UCB is lipid-soluble, bound to albumin in blood – toxic at high levels (kernicterus)", False),
  ("", False),
  ("HEPATIC CONJUGATION:", True),
  ("  • UCB → hepatocyte → conjugated with glucuronic acid via UGT1A1 → water-soluble", False),
  ("  • Conjugated bilirubin (CB) secreted into bile canaliculi", False),
  ("  • Excreted in bile → intestine → stercobilinogen (yellow stool colour)", False),
  ("  • Gut bacteria convert to urobilinogen → absorbed → kidney → urobilin (yellow urine)", False),
  ("", False),
  ("CLINICAL SIGNIFICANCE OF TYPE:", True),
  ("  • Unconjugated (indirect) hyperbilirubinemia:", False),
  ("    – Overproduction (hemolysis), impaired uptake (Gilbert's), impaired conjugation (Crigler-Najjar)", False),
  ("    – Pale stool ABSENT; urine dark if CB present", False),
  ("  • Conjugated (direct) hyperbilirubinemia:", False),
  ("    – Impaired excretion / biliary obstruction / hepatocellular disease", False),
  ("    – ALWAYS pathological – requires investigation", False),
  ("    – Pale/acholic stools + dark urine (conjugated = water soluble → excreted in urine)", False),
  ("", False),
  ("NORMAL VALUES:", True),
  ("  • Total bilirubin: < 1.0 mg/dL; Direct (conjugated): < 0.3 mg/dL", False),
  ("  • Clinical jaundice visible at > 5 mg/dL (adults), > 7 mg/dL (neonates)", False),
],
font_size=15)

# Slide 17 – Classification
content_slide(prs, "Classification of Jaundice with HSM in Children",
two_col=True,
bullets=[
  ("PRE-HEPATIC (Unconjugated) + Splenomegaly:", True),
  ("  • Hemolytic anemias:", False),
  ("    – Thalassemia major/intermedia", False),
  ("    – Sickle cell disease", False),
  ("    – Hereditary spherocytosis", False),
  ("    – G6PD deficiency (episodic)", False),
  ("    – Autoimmune hemolytic anemia (AIHA)", False),
  ("  • Malaria: intravascular hemolysis + HSM", False),
  ("  • Neonatal isoimmune hemolysis (Rh, ABO incompatibility)", False),
  ("", False),
  ("HEPATIC (Hepatocellular) + HSM:", True),
  ("  • Infective:", False),
  ("    – Viral hepatitis A/B/C/E, EBV, CMV", False),
  ("    – Leptospirosis, typhoid, dengue", False),
  ("  • Metabolic/storage:", False),
  ("    – Wilson's disease (acute/chronic)", False),
  ("    – Tyrosinemia type I (acute liver failure)", False),
  ("    – GSD, Niemann-Pick", False),
  ("  • Autoimmune hepatitis", False),
],
col2_bullets=[
  ("POST-HEPATIC (Cholestatic) + HSM:", True),
  ("  • Biliary atresia (neonatal cholestasis)", False),
  ("  • Choledochal cyst", False),
  ("  • Primary sclerosing cholangitis (PSC)", False),
  ("  • Alagille syndrome (paucity of bile ducts)", False),
  ("  • Caroli disease", False),
  ("", False),
  ("MIXED (Hepatosplenic disease):", True),
  ("  • Cirrhosis with portal hypertension:", False),
  ("    – Hepatomegaly (initially) → small liver + massive spleen", False),
  ("    – Biliary atresia, CF, Wilson's, alpha-1-AT deficiency", False),
  ("  • Portal hypertension (non-cirrhotic):", False),
  ("    – EHPVO (extrahepatic portal vein obstruction)", False),
  ("    – Congenital hepatic fibrosis", False),
  ("", False),
  ("NEONATAL-SPECIFIC:", True),
  ("  • Physiological jaundice: Day 2–7, UCB, self-limiting, NO HSM", False),
  ("  • Pathological neonatal jaundice:", False),
  ("    – Onset day 1: hemolytic (Rh/ABO); TORCH infections → HSM", False),
  ("    – Prolonged (>14 days): biliary atresia, neonatal hepatitis, hypothyroidism", False),
],
note="Conjugated hyperbilirubinemia (direct > 1 mg/dL or > 20% of total) in any age is ALWAYS pathological.")

# Slide 18 – Neonatal Jaundice with HSM
content_slide(prs, "Neonatal Jaundice with Hepatosplenomegaly – Key Approach",
two_col=True,
bullets=[
  ("EARLY ONSET (Day 1–3) + HSM:", True),
  ("  • TORCH Infections:", False),
  ("    – CMV: most common congenital infection", False),
  ("    – Rubella: cataracts, cardiac, deafness, HSM, IUGR", False),
  ("    – Toxoplasma: chorioretinitis, hydrocephalus, intracranial calcification", False),
  ("    – Syphilis: HSM, skin lesions, snuffles, bone changes", False),
  ("    – HSV: HSM, vesicular rash, encephalitis", False),
  ("  • Rh/ABO isoimmunization: severe jaundice, hydrops fetalis", False),
  ("  • Sepsis: HSM + hypotension + DIC", False),
  ("", False),
  ("INVESTIGATIONS FOR NEONATAL HSM + JAUNDICE:", True),
  ("  • Direct Coombs test (DCT)", False),
  ("  • TORCH titers (IgM specific), CMV PCR urine/blood", False),
  ("  • Blood culture, urine culture, CRP, CBC", False),
  ("  • Urine: reducing substances (galactosemia)", False),
  ("  • TSH (hypothyroidism)", False),
  ("  • Alpha-fetoprotein (hepatoblastoma, tyrosinemia)", False),
],
col2_buttons=[
  ("PROLONGED NEONATAL JAUNDICE (>14 days) + HSM:", True),
  ("  • Biliary atresia: acholic stools, progressive HSM", False),
  ("    – Gold standard diagnosis: intraoperative cholangiogram", False),
  ("    – Kasai within 60 days → better outcome", False),
  ("  • Neonatal hepatitis: viral, metabolic, idiopathic", False),
  ("  • Galactosemia: galactose + E. coli sepsis + liver failure", False),
  ("    – Reducing substances in urine, avoid lactose", False),
  ("  • Alpha-1-antitrypsin deficiency: PAS+ granules in liver biopsy", False),
  ("  • Alagille syndrome: paucity of intrahepatic bile ducts", False),
  ("    – Butterfly vertebrae, peripheral PS, posterior embryotoxon", False),
  ("", False),
  ("RULE OF THUMB:", True),
  ("  • Any neonate with conjugated jaundice + HSM → URGENT workup", False),
  ("  • Refer to pediatric hepatology if biliary atresia suspected", False),
  ("  • Acholic stool card screening recommended by IAP/AAP", False),
],
font_size=15, note="Neonatal HSM + jaundice is a medical emergency until proven otherwise. (Nelson 21e, Ch. 384 & 120)")

# Slide 19 – Jaundice + HSM: Specific Conditions
content_slide(prs, "Specific Conditions: Jaundice + HSM in Children",
two_col=True,
bullets=[
  ("VIRAL HEPATITIS WITH HSM:", True),
  ("  • Hepatitis A: Acute self-limiting; HSM, elevated transaminases", False),
  ("    – HAV IgM diagnostic; supportive treatment", False),
  ("  • Hepatitis B: Acute or chronic; HBsAg + in chronic carriers", False),
  ("    – HSM + cholestasis in chronic HBV; risk of HCC", False),
  ("  • EBV/Infectious Mononucleosis:", False),
  ("    – Triad: fever + pharyngitis + lymphadenopathy; 50% HSM", False),
  ("    – Atypical lymphocytes, monospot test, EBV-VCA IgM", False),
  ("  • Dengue hepatitis: transaminitis, thrombocytopenia, dengue NS1/IgM", False),
  ("  • Leptospirosis (Weil's disease): jaundice + AKI + HSM + conjunctival suffusion", False),
  ("", False),
  ("AUTOIMMUNE HEPATITIS (AIH):", True),
  ("  • Type 1 (ANA, anti-SMA +) and Type 2 (anti-LKM1 +)", False),
  ("  • Young females predominate; HSM + jaundice + elevated IgG", False),
  ("  • Histology: interface hepatitis, rosette formation", False),
  ("  • Treatment: Prednisolone + Azathioprine", False),
],
col2_bullets=[
  ("WILSON'S DISEASE:", True),
  ("  • Juvenile cirrhosis presentation: HSM + jaundice + KF rings", False),
  ("  • Coombs-negative hemolytic anemia + acute liver failure", False),
  ("  • Low ceruloplasmin (<20 mg/dL), ↑ 24h urine Cu (>100 μg/day)", False),
  ("  • Liver biopsy: rhodanine stain for copper", False),
  ("  • Treatment: D-penicillamine / Trientine + Zinc maintenance", False),
  ("", False),
  ("PRIMARY SCLEROSING CHOLANGITIS (PSC):", True),
  ("  • Associated with IBD (esp. ulcerative colitis) in children", False),
  ("  • MRCP: beaded appearance of bile ducts", False),
  ("  • Progressive cholestasis → cirrhosis; risk of cholangiocarcinoma", False),
  ("", False),
  ("SYSTEMIC CAUSES WITH JAUNDICE + HSM:", True),
  ("  • SLE: hemolytic anemia + hepatitis + HSM + malar rash + ANA +", False),
  ("  • Systemic JIA: Still's disease – spiking fever + rash + arthritis + HSM", False),
  ("  • HLH: hyperbilirubinemia + HSM + hyperferritinemia (life-threatening)", False),
  ("  • Langerhans Cell Histiocytosis: jaundice + HSM + bone lesions + skin rash", False),
  ("  • Malignant infiltration: hepatoblastoma, neuroblastoma with liver metastasis", False),
],
note="Wilson's disease should be excluded in any child >3 years with unexplained liver disease. (Scott's Pediatrics)")

# Slide 20 – Investigations for Jaundice + HSM
content_slide(prs, "Investigations for Jaundice with HSM – Systematic Approach",
two_col=True,
bullets=[
  ("MANDATORY FIRST LINE:", True),
  ("  • Bilirubin: Total, Direct (conjugated), Indirect", False),
  ("  • LFT: ALT, AST, ALP, GGT, albumin, total protein", False),
  ("  • PT/INR, aPTT (synthetic function)", False),
  ("  • CBC + peripheral smear (hemolytic vs infiltrative)", False),
  ("  • Blood group, Coombs test (DCT/ICT)", False),
  ("  • Urine: bile salts, bile pigments, urobilinogen, reducing substances", False),
  ("  • USG abdomen with Doppler: liver size/echo, biliary anatomy, portal vein", False),
  ("  • Stool colour observation (acholic → biliary obstruction)", False),
  ("", False),
  ("SECOND LINE – Based on Suspected Cause:", True),
  ("  • Hemolytic: Reticulocyte count, Hb electrophoresis, osmotic fragility, G6PD assay", False),
  ("  • Viral: HAV IgM, HBsAg, HCV RNA, EBV/CMV IgM, dengue NS1+IgM", False),
  ("  • Metabolic: Ceruloplasmin, 24h urine Cu, alpha-fetoprotein, serum ammonia", False),
  ("  • Autoimmune: ANA, ASMA, anti-LKM1, anti-SLA, IgG levels", False),
  ("  • Neonatal: TORCH titers, urine CMV PCR, urine reducing substances, TSH", False),
],
col2_bullets=[
  ("IMAGING:", True),
  ("  • USG + Doppler: First choice – biliary anatomy, portal vein thrombosis", False),
  ("  • MRCP: Biliary tree anatomy – preferred over ERCP in children", False),
  ("  • HIDA scan (Hepatobiliary scintigraphy): Biliary atresia vs neonatal hepatitis", False),
  ("    – Non-secretion of tracer into intestine = biliary atresia", False),
  ("  • CT/MRI liver: Portal hypertension, infiltrative disease, tumors", False),
  ("  • Fibroscan/Shear wave elastography: Liver fibrosis assessment", False),
  ("", False),
  ("LIVER BIOPSY (Gold standard for parenchymal disease):", True),
  ("  • Biliary atresia: bile duct proliferation, bile plugging, fibrosis", False),
  ("  • Neonatal hepatitis: multinucleated giant cells", False),
  ("  • Autoimmune hepatitis: interface hepatitis, plasma cell infiltrate", False),
  ("  • Storage disorders: storage vacuoles, PAS+ granules", False),
  ("  • Wilson's: Rhodanine +, elevated hepatic copper (>250 μg/g)", False),
  ("  • Timing: After correction of coagulopathy; prefer liver biopsy EARLY", False),
  ("", False),
  ("METABOLIC SCREEN (Neonatal):", True),
  ("  • Tandem mass spectrometry (NBS panel): fatty acid oxidation defects, organic acidemias", False),
  ("  • Succinylacetone in urine: Tyrosinemia type I", False),
],
note="In cholestatic jaundice in infancy: always do HIDA scan + liver biopsy to differentiate biliary atresia from neonatal hepatitis.")

# Slide 21 – Diagnostic Algorithm Jaundice + HSM
content_slide(prs, "Diagnostic Algorithm: Jaundice + Hepatosplenomegaly in Children",
[
  ("STEP 1 – Confirm jaundice type:", True),
  ("  Serum bilirubin (total, direct, indirect) → Is direct (conjugated) > 1 mg/dL or > 20% of total?", False),
  ("  ➤ YES = Conjugated → Hepatocellular / Cholestatic / Biliary disease", False),
  ("  ➤ NO = Unconjugated → Hemolysis / Gilbert's / Crigler-Najjar", False),
  ("", False),
  ("STEP 2 – Unconjugated hyperbilirubinemia + HSM:", True),
  ("  CBC + smear → hemolysis? ➤ Hb electrophoresis, Coombs, G6PD, osmotic fragility", False),
  ("  Malaria smear + RDT, dengue serology, EBV IgM", False),
  ("", False),
  ("STEP 3 – Conjugated hyperbilirubinemia + HSM:", True),
  ("  LFT pattern → Hepatocellular (ALT↑↑ > ALP) vs Cholestatic (ALP↑↑ > ALT)", False),
  ("  ➤ Hepatocellular: Viral panel, autoimmune panel, Wilson's workup, metabolic screen", False),
  ("  ➤ Cholestatic: USG + MRCP → dilated ducts (obstruction) vs normal (intrahepatic)", False),
  ("    – Normal ducts + neonatal → biliary atresia vs neonatal hepatitis → HIDA scan → liver biopsy", False),
  ("    – Dilated ducts → choledochal cyst, choledocholithiasis, PSC", False),
  ("", False),
  ("STEP 4 – Is there portal hypertension?", True),
  ("  Splenomegaly + ascites + dilated veins + varices → Doppler USG portal vein", False),
  ("  ➤ EHPVO (neonatal umbilical catheter, sepsis) vs Cirrhosis vs Congenital hepatic fibrosis", False),
  ("", False),
  ("STEP 5 – Is it a systemic disease?", True),
  ("  Fever + lymphadenopathy + cytopenias → HLH workup (ferritin, fibrinogen, BM biopsy)", False),
  ("  Arthritis + rash → SLE workup (ANA, complement), systemic JIA (high ferritin)", False),
],
font_size=15, note="In any age: conjugated jaundice + HSM + acholic stools = biliary emergency until proven otherwise.")

# Slide 22 – Portal Hypertension Special
content_slide(prs, "Portal Hypertension with Jaundice and HSM in Children",
two_col=True,
bullets=[
  ("DEFINITION:", True),
  ("  • Portal venous pressure >10 mmHg (hepatic venous pressure gradient >5 mmHg)", False),
  ("  • Clinically significant when HVPG > 10 mmHg", False),
  ("", False),
  ("CAUSES IN CHILDREN:", True),
  ("  Pre-hepatic (most common in India):", False),
  ("  • EHPVO (Extrahepatic Portal Vein Obstruction)", False),
  ("    – Neonatal umbilical vein catheterization, sepsis, dehydration", False),
  ("    – Cavernous transformation of portal vein on Doppler", False),
  ("  Hepatic:", False),
  ("  • Cirrhosis (biliary atresia, Wilson's, CF, AIH)", False),
  ("  • Congenital hepatic fibrosis (AR)", False),
  ("  • Schistosomiasis (periportal fibrosis)", False),
  ("  Post-hepatic:", False),
  ("  • Budd-Chiari syndrome (hepatic vein thrombosis)", False),
  ("  • Constrictive pericarditis, cardiac failure", False),
],
col2_bullets=[
  ("CLINICAL FEATURES:", True),
  ("  • Massive splenomegaly (often > hepatomegaly in EHPVO)", False),
  ("  • Hypersplenism: pancytopenia", False),
  ("  • Variceal bleeding (hematemesis, melena): life-threatening", False),
  ("  • Ascites (more in cirrhosis than EHPVO)", False),
  ("  • Caput medusae, dilated abdominal wall veins", False),
  ("  • Jaundice: variable (mild in EHPVO; significant in cirrhosis)", False),
  ("", False),
  ("INVESTIGATIONS:", True),
  ("  • USG + Doppler: Portal vein diameter, flow direction, cavernoma", False),
  ("  • Upper GI endoscopy: Esophageal/gastric varices grading", False),
  ("  • CECT abdomen: Portal venous anatomy", False),
  ("  • Liver biopsy: Cirrhosis vs CHF vs normal liver (EHPVO)", False),
  ("", False),
  ("MANAGEMENT:", True),
  ("  • Acute bleed: Octreotide IV, Endoscopic variceal ligation (EVL)", False),
  ("  • Prophylaxis: Propranolol, EVL", False),
  ("  • Definitive (EHPVO): Meso-Rex bypass (preferred)", False),
  ("  • Liver transplant: End-stage cirrhosis", False),
],
note="EHPVO is the most common cause of variceal bleeding and massive splenomegaly in Indian children. (Scott's Pediatrics)")

# Slide 23 – Specific Conditions Quick Reference Table
content_slide(prs, "Quick Reference: Jaundice + HSM – Diagnosis at a Glance",
[
  ("CONDITION                       |  KEY FEATURES                              |  DIAGNOSTIC CLUE", True),
  ("─────────────────────────────────────────────────────────────────────────────────────────────────────", False),
  ("Malaria                         |  Fever spikes, pallor, massive spleen       |  Thick smear / RDT / PCR", False),
  ("Kala-azar (VL)                  |  Prolonged fever, wasting, massive spleen  |  rK39 antigen, splenic aspirate", False),
  ("Viral Hepatitis A               |  Acute, self-limiting, contact hx          |  HAV IgM", False),
  ("EBV (Infect. Mononucleosis)     |  Pharyngitis, LAN, HSM, atypical lymphs    |  Monospot, EBV VCA IgM", False),
  ("Thalassemia Major               |  Pallor, frontal bossing, target cells      |  Hb electrophoresis", False),
  ("ALL                             |  Bone pains, bleeding, blast cells          |  Bone marrow biopsy", False),
  ("Wilson's Disease                |  KF rings, neuropsych, hemolysis            |  Ceruloplasmin, 24h urine Cu", False),
  ("Biliary Atresia                 |  Neonatal, acholic stools, CB↑              |  HIDA scan + liver biopsy", False),
  ("Gaucher's Disease               |  Massive spleen > liver, BM 'crumpled'     |  Glucocerebrosidase assay", False),
  ("Autoimmune Hepatitis            |  Young female, ↑IgG, interface hepatitis   |  ANA/ASMA/LKM1, liver Bx", False),
  ("HLH                             |  Pancytopenia, fever, ↑↑ferritin           |  Ferritin >10,000, BM Bx", False),
  ("EHPVO                           |  Variceal bleed, normal LFT, cavernoma     |  Doppler USG portal vein", False),
  ("Tyrosinemia Type I              |  Liver failure, AFP↑↑, hepatoblastoma risk  |  Urine succinylacetone", False),
  ("SLE                             |  Hemolysis, rash, arthritis, ANA+          |  ANA, anti-dsDNA, complement", False),
],
font_size=13.5, note="This table serves as a quick clinical reference. Always correlate with full clinical picture.")

# Slide 24 – Management of Jaundice with HSM
content_slide(prs, "Management of Jaundice with HSM – Targeted Treatment",
two_col=True,
bullets=[
  ("NEONATAL JAUNDICE + HSM:", True),
  ("  • Phototherapy: Unconjugated NNJ per AAP 2022 thresholds", False),
  ("  • Exchange transfusion: Severe hemolysis/kernicterus risk", False),
  ("  • Biliary atresia: Kasai portoenterostomy < 60 days of life", False),
  ("  • TORCH: CMV – ganciclovir; Syphilis – penicillin G", False),
  ("  • Galactosemia: Lactose-free formula immediately", False),
  ("  • Tyrosinemia: NTBC (nitisinone) + low-phenylalanine/tyrosine diet", False),
  ("", False),
  ("VIRAL/INFECTIOUS JAUNDICE:", True),
  ("  • Hepatitis A/E: Supportive care, hydration, nutrition", False),
  ("  • Hepatitis B: Tenofovir / Entecavir (chronic); close follow-up", False),
  ("  • Leptospirosis: Penicillin G IV / Amoxicillin (mild)", False),
  ("  • EBV: Supportive; corticosteroids if severe airway/thrombocytopenia", False),
  ("", False),
  ("METABOLIC:", True),
  ("  • Wilson's: Penicillamine + pyridoxine; zinc (maintenance)", False),
  ("    – Liver transplant: Fulminant Wilson's, decompensated cirrhosis", False),
  ("  • Alpha-1-AT deficiency: Supportive; liver transplant for cirrhosis", False),
],
col2_bullets=[
  ("HEMOLYTIC JAUNDICE + HSM:", True),
  ("  • Identify and treat trigger (infection, drugs, fava beans)", False),
  ("  • Transfuse if Hb <7 g/dL or hemodynamic compromise", False),
  ("  • Iron chelation if transfusion-dependent (thalassemia)", False),
  ("  • Stem cell transplant: Curative for thalassemia and SCD", False),
  ("  • Splenectomy: After 5 yrs, with vaccination; hereditary spherocytosis", False),
  ("", False),
  ("CHOLESTATIC JAUNDICE:", True),
  ("  • Fat-soluble vitamin supplementation (A, D, E, K)", False),
  ("  • Ursodeoxycholic acid: Cholestasis, Alagille syndrome, PSC", False),
  ("  • Pruritus: Rifampicin, cholestyramine, naltrexone", False),
  ("  • Biliary obstruction (choledochal cyst): Surgical excision", False),
  ("", False),
  ("LIVER TRANSPLANTATION (Nelson 21e):", True),
  ("  • Indications: End-stage liver disease, acute liver failure,", False),
  ("    metabolic disease with systemic complications", False),
  ("  • Biliary atresia: Most common indication in pediatric transplant", False),
  ("  • Outcomes: 5-year survival >85% at specialized centers", False),
  ("  • Living donor transplant: Preferred in children (size matching)", False),
  ("  • Post-transplant: Tacrolimus + MMF immunosuppression", False),
],
note="Liver transplantation is life-saving for end-stage liver disease; early referral to pediatric hepatology is key.")

# Slide 25 – When to Refer
content_slide(prs, "Red Flags & When to Refer to Pediatric Hepatology / Tertiary Care",
[
  ("RED FLAG SIGNS – Immediate Referral / Hospitalization:", True),
  ("  🔴 Conjugated jaundice in a neonate (any age) → rule out biliary atresia (urgent <60 days)", False),
  ("  🔴 Acute liver failure: jaundice + coagulopathy (INR >2) + encephalopathy", False),
  ("  🔴 Variceal bleeding: hematemesis + splenomegaly → emergency endoscopy + octreotide", False),
  ("  🔴 Suspected HLH: cytopenias + fever + HSM + ferritin >500 μg/L", False),
  ("  🔴 Suspected leukemia: blast cells on smear + HSM + bone pains", False),
  ("  🔴 Massive splenomegaly + risk of splenic rupture (EBV, kala-azar)", False),
  ("  🔴 Hypersplenism with symptomatic cytopenias (Hb < 7 g/dL, plt < 20,000)", False),
  ("  🔴 Suspected Wilson's disease: acute hemolytic anemia + liver failure (Coombs-negative)", False),
  ("", False),
  ("YELLOW FLAGS – Urgent Workup Within 48 Hours:", True),
  ("  🟡 Prolonged neonatal jaundice (>14 days) with conjugated fraction", False),
  ("  🟡 Unexplained HSM with failure to thrive / weight loss / developmental regression", False),
  ("  🟡 Unexplained splenomegaly > 5 cm with fever for > 2 weeks", False),
  ("  🟡 Suspected storage disorder (coarse facies + organomegaly + neurodegeneration)", False),
  ("  🟡 Portal hypertension signs without prior diagnosis", False),
  ("", False),
  ("WHEN TO ADMIT:", True),
  ("  • Hepatic encephalopathy, coagulopathy, acute variceal bleed, severe hemolysis", False),
  ("  • Suspected malignancy, HLH, fulminant hepatic failure", False),
],
font_size=15.5, note="When in doubt, refer early. Outcomes in biliary atresia, HLH, and leukemia are time-dependent.")

# Slide 26 – Summary Part A
content_slide(prs, "Summary – Approach to HSM in Children (Nelson 21e / Scott's Pediatrics)",
[
  ("1. HSM is always pathological beyond early neonatal period – mandates systematic evaluation", True),
  ("", False),
  ("2. Age of onset guides differential:", True),
  ("   Neonate: TORCH, biliary atresia, metabolic   |   Infant: Storage, metabolic, hematological", False),
  ("   Child: Infections (tropical), leukemia, portal HTN   |   Adolescent: Viral hepatitis, autoimmune, Wilson's", False),
  ("", False),
  ("3. Clinical examination features narrow differential significantly:", True),
  ("   Massive splenomegaly: kala-azar, malaria, thalassemia, CML, Gaucher's", False),
  ("   Liver > spleen: hepatocellular disease, metabolic, infective hepatitis", False),
  ("   Spleen > liver: portal hypertension, hematological, storage disorders", False),
  ("", False),
  ("4. Investigations: Start with CBC + smear + LFT + USG abdomen", True),
  ("   Progress to targeted tests based on clinical clues", False),
  ("", False),
  ("5. Treatment is cause-directed:", True),
  ("   Infections → antimicrobials   |   Malignancy → chemotherapy   |   Storage → ERT / BMT", False),
  ("   Portal HTN → EVL / Meso-Rex bypass / Liver transplant", False),
  ("", False),
  ("6. Early diagnosis and referral are key to good outcomes", True),
  ("   Biliary atresia (Kasai <60 days)  |  HLH (HLH-2004 protocol)  |  Leukemia (BFM protocol)", False),
],
font_size=16)

# Slide 27 – Summary Part B
content_slide(prs, "Summary – Jaundice with HSM in Children",
[
  ("1. Determine jaundice type first: Unconjugated vs Conjugated bilirubin", True),
  ("   Conjugated = ALWAYS pathological; requires urgent investigation", False),
  ("", False),
  ("2. Key algorithm:", True),
  ("   Unconjugated + HSM → hemolysis → CBC, smear, electrophoresis, Coombs", False),
  ("   Conjugated + hepatic (ALT↑) → viral hepatitis, autoimmune, metabolic", False),
  ("   Conjugated + cholestatic (ALP↑) → biliary atresia, PSC, choledochal cyst", False),
  ("", False),
  ("3. Neonatal jaundice + HSM:", True),
  ("   TORCH screen, metabolic screen, Coombs test, HIDA scan, liver biopsy", False),
  ("   Biliary atresia → Kasai < 60 days is the single most important intervention", False),
  ("", False),
  ("4. Portal hypertension:", True),
  ("   EHPVO most common cause in India; variceal bleeding = emergency", False),
  ("   Doppler USG + endoscopy; EVL + propranolol; consider Meso-Rex bypass", False),
  ("", False),
  ("5. Do not miss:", True),
  ("   Wilson's disease (KF rings + low ceruloplasmin)  |  HLH (ferritin >10,000)", False),
  ("   Malignancy (blast cells + HSM + bone pains)  |  Biliary atresia (acholic stools)", False),
  ("", False),
  ("6. Liver transplantation: curative for end-stage liver disease in children; >85% 5-year survival", True),
],
font_size=16)

# Slide 28 – References
ref_slide(prs)

# ─── SAVE ────────────────────────────────────────────────────────────────────
output_path = "/tmp/workspace/hsp-presentation/Hepatosplenomegaly_Jaundice_Children.pptx"
buf = BytesIO()
prs.save(buf)
with open(output_path, "wb") as f:
    f.write(buf.getvalue())

print(f"Saved: {output_path}")
print(f"Slides: {len(prs.slides)}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/hsp-presentation/build_pptx.py'