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 io import BytesIO

# Color palette
DARK_BG    = RGBColor(0x1A, 0x1A, 0x2E)   # deep navy
ACCENT     = RGBColor(0xC0, 0x5C, 0x1E)   # rust/bronze (iron colour)
ACCENT2    = RGBColor(0xE8, 0xA8, 0x5A)   # gold
WHITE      = RGBColor(0xFF, 0xFF, 0xFF)
LIGHT_GREY = RGBColor(0xE0, 0xE0, 0xE8)
MID_GREY   = RGBColor(0xA0, 0xA8, 0xB8)
SLIDE_BG   = RGBColor(0x16, 0x21, 0x3E)   # slightly lighter navy

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

blank_layout = prs.slide_layouts[6]

def hex_fill(shape, color: RGBColor):
    fill = shape.fill
    fill.solid()
    fill.fore_color.rgb = color

def add_rect(slide, x, y, w, h, color: RGBColor):
    shape = slide.shapes.add_shape(1, Inches(x), Inches(y), Inches(w), Inches(h))
    hex_fill(shape, color)
    shape.line.fill.background()
    return shape

def add_textbox(slide, text, x, y, w, h,
                font_size=18, bold=False, color=WHITE,
                align=PP_ALIGN.LEFT, italic=False, wrap=True):
    tb = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf = tb.text_frame
    tf.word_wrap = wrap
    tf.auto_size = None
    tf.margin_left  = Inches(0.05)
    tf.margin_right = Inches(0.05)
    tf.margin_top   = Inches(0.03)
    tf.margin_bottom= Inches(0.03)
    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 tf

def add_bullet_slide(slide, title_text, bullets, source="Sleisenger & Fordtran, Ch.75"):
    """Add background, title bar and bullet list to a blank slide."""
    # Background
    bg = slide.shapes.add_shape(1, 0, 0, prs.slide_width, prs.slide_height)
    hex_fill(bg, SLIDE_BG)
    bg.line.fill.background()

    # Top accent bar
    add_rect(slide, 0, 0, 13.333, 0.08, ACCENT)

    # Title area
    add_rect(slide, 0, 0.08, 13.333, 0.90, DARK_BG)
    add_textbox(slide, title_text,
                x=0.35, y=0.08, w=12.6, h=0.90,
                font_size=28, bold=True, color=ACCENT2,
                align=PP_ALIGN.LEFT)

    # Divider line
    add_rect(slide, 0.35, 1.05, 12.63, 0.04, ACCENT)

    # Bullets
    bullet_y_start = 1.18
    bullet_h       = (7.5 - bullet_y_start - 0.55) / max(len(bullets), 1)
    bullet_h       = min(bullet_h, 1.0)

    for i, bullet in enumerate(bullets):
        y = bullet_y_start + i * bullet_h
        # Bullet dot
        dot = slide.shapes.add_shape(9,  # oval
                                     Inches(0.30), Inches(y + bullet_h*0.38),
                                     Inches(0.13), Inches(0.13))
        hex_fill(dot, ACCENT)
        dot.line.fill.background()

        add_textbox(slide, bullet,
                    x=0.55, y=y, w=12.2, h=bullet_h,
                    font_size=17, bold=False, color=LIGHT_GREY,
                    align=PP_ALIGN.LEFT)

    # Source tag
    add_textbox(slide, source,
                x=0.35, y=7.10, w=12.0, h=0.35,
                font_size=11, italic=True, color=MID_GREY,
                align=PP_ALIGN.RIGHT)


# ─────────────────────────────────────────────
#  SLIDE DATA  (max 6 bullets per slide)
# ─────────────────────────────────────────────
slides_data = [
    # 1 – Title slide (handled separately)
    None,

    # 2
    ("Definition & Overview",
     ["Hemochromatosis (HH) = group of disorders causing systemic iron overload",
      "Iron accumulates in parenchymal cells: liver, pancreas, heart, pituitary, joints",
      "Liver is always the principal recipient of excess iron",
      "HFE-related HH is the most common form; autosomal recessive",
      "Normal body iron ~4 g; symptomatic HH may accumulate 20–40 g",
      "Excess iron causes oxidative damage via free-radical generation"]),

    # 3
    ("Classification of Iron Overload (Box 75.1)",
     ["HFE-Related HH (Type 1): C282Y homozygosity; C282Y/H63D compound heterozygosity",
      "Type 2A: Hemojuvelin (HJV) mutations — juvenile HH (severe, childhood onset)",
      "Type 2B: Hepcidin (HAMP) mutations — rare juvenile HH",
      "Type 3: Transferrin receptor 2 (TFR2) mutations — autosomal recessive",
      "Type 4: Ferroportin (SLC40A1) mutations — loss- or gain-of-function",
      "Secondary: iron-loading anemias, transfusions, chronic liver disease, dietary excess"]),

    # 4
    ("Genetics — HFE Gene",
     ["HFE gene located on chromosome 6p; encodes atypical MHC class I protein",
      "C282Y (Cys282Tyr): most common pathogenic mutation; found in ~85–90% of cases",
      "H63D (His63Asp): minor mutation; ~10% of compound heterozygotes (C282Y/H63D) develop iron overload",
      "HFE protein regulates hepcidin expression and transferrin receptor signaling",
      "Prevalence of C282Y homozygosity: ~1 in 200–400 in northern European populations",
      "Penetrance is incomplete: most C282Y homozygotes do not develop clinical disease"]),

    # 5
    ("Pathophysiology — Hepcidin Axis",
     ["Hepcidin is a hepatic peptide hormone: master regulator of iron homeostasis",
      "Hepcidin binds ferroportin, causing its internalization and degradation",
      "Reduced hepcidin → ferroportin unrestrained → excess iron export from enterocytes & macrophages",
      "In HFE-related HH: mutant HFE → impaired hepcidin upregulation → chronic excess absorption",
      "Result: duodenal iron absorption 3–4× normal; transferrin saturation persistently elevated",
      "Hemojuvelin (HJV) is an important upstream regulator of hepcidin expression"]),

    # 6
    ("Pathophysiology — Iron Toxicity",
     ["Non-transferrin-bound iron (NTBI) increases as transferrin becomes saturated",
      "NTBI generates reactive oxygen species (ROS) via Fenton reaction",
      "ROS causes lipid peroxidation, mitochondrial dysfunction, and DNA damage",
      "Stellate cell activation → periportal fibrosis → cirrhosis if untreated",
      "Iron deposits in hepatocyte lysosomes cause lysosomal membrane peroxidation",
      "Cardiac iron overload leads to arrhythmias, dilated cardiomyopathy, and heart failure"]),

    # 7
    ("Epidemiology",
     ["Most common genetic liver disease in persons of northern European ancestry",
      "C282Y allele frequency ~6–10% in northern Europeans; ~1 in 300 are homozygotes",
      "Clinical expression higher in men (10:1 vs women before menopause)",
      "Women protected by menstruation and pregnancy (iron loss offsets accumulation)",
      "Symptoms typically appear between age 40–60 in men; post-menopausal women",
      "African iron overload (Bantu siderosis): dietary source + genetic susceptibility in sub-Saharan Africa"]),

    # 8
    ("Clinical Features — Early",
     ["Often asymptomatic in early stages; detected on routine biochemistry",
      "Fatigue and lethargy: most common presenting symptoms (non-specific)",
      "Arthralgias: especially MCP joints 2 & 3 ('iron fist') — characteristic early clue",
      "Serum ferritin and transferrin saturation elevated before organ damage",
      "Hepatomegaly (without jaundice) may be first physical sign",
      "Elevated serum aminotransferases (ALT/AST) in ~75% of symptomatic patients"]),

    # 9
    ("Clinical Features — Advanced Organ Damage",
     ["Liver: hepatic fibrosis → cirrhosis; HCC risk ↑200× in cirrhotic HH patients",
      "Pancreas: diabetes mellitus ('bronze diabetes') from islet cell destruction",
      "Skin: bronze/gray-brown hyperpigmentation; accentuated over sun-exposed areas",
      "Heart: dilated cardiomyopathy, conduction defects, arrhythmias, heart failure",
      "Pituitary/gonads: hypogonadotropic hypogonadism → loss of libido, impotence, amenorrhea",
      "Joints: chondrocalcinosis (calcium pyrophosphate deposition), destructive arthropathy"]),

    # 10
    ("The Classic Triad",
     ["Classic triad: cirrhosis + diabetes mellitus + skin bronzing",
      "Triad represents advanced, end-organ damage — now less commonly seen at diagnosis",
      "Earlier diagnosis via screening has shifted presentation to milder phenotype",
      "Skin bronzing is due to both melanin increase and hemosiderin deposition",
      "'Bronze diabetes' nomenclature coined from co-occurrence of bronze skin and glucose intolerance",
      "Testicular atrophy and loss of secondary sex characteristics may accompany the triad"]),

    # 11
    ("Juvenile Hemochromatosis (Type 2)",
     ["Rare; caused by mutations in HJV (type 2A) or HAMP (type 2B) genes",
      "Presents in 2nd–3rd decade of life with rapid, severe iron overload",
      "Predominant features: hypogonadism and cardiomyopathy (rather than cirrhosis)",
      "HJV gene on chromosome 1q; hemojuvelin is key regulator of hepcidin",
      "Earlier age of organ damage due to lower hepcidin levels compared to Type 1",
      "Without treatment, can lead to heart failure and death before age 30"]),

    # 12
    ("Ferroportin Disease (Type 4)",
     ["Caused by mutations in SLC40A1 gene encoding ferroportin (iron exporter)",
      "Loss-of-function mutations: iron accumulates in macrophages (Kupffer cells, not hepatocytes)",
      "Gain-of-function mutations: hepcidin-resistant ferroportin → hepatocyte iron loading",
      "Loss-of-function (classical ferroportin disease): generally less pathogenic",
      "Gain-of-function: phenotype similar to HFE-related HH (hepatocyte iron deposition)",
      "Autosomal dominant inheritance distinguishes it from other HH types"]),

    # 13
    ("Laboratory Diagnosis — Serum Tests",
     ["Transferrin saturation (TS) = serum iron ÷ TIBC × 100%; threshold ≥45% is abnormal",
      "Fasting TS ≥45% is the single most sensitive screening test for HFE-related HH",
      "Serum ferritin >300 ng/mL (men) or >200 ng/mL (women) raises suspicion",
      "Serum ferritin correlates with body iron stores but is an acute-phase reactant (falsely elevated in inflammation)",
      "LFTs: elevated ALT/AST common; bilirubin and PT usually normal until late cirrhosis",
      "Combination of elevated TS + elevated ferritin: sensitivity ~94% for symptomatic HH"]),

    # 14
    ("Genetic Testing — HFE Mutation Analysis",
     ["HFE genotyping is indicated when TS ≥45% and/or serum ferritin is elevated",
      "C282Y homozygote + elevated iron indices = HFE-related HH confirmed (no biopsy needed if ferritin <1000)",
      "C282Y/H63D compound heterozygote: ~10% develop iron overload; other causes must be excluded",
      "H63D homozygote or C282Y heterozygote: iron overload likely secondary to other disease",
      "Negative HFE mutations with iron overload: consider non-HFE HH or secondary causes",
      "Family screening: first-degree relatives of C282Y homozygotes should be tested"]),

    # 15
    ("Liver Biopsy — Role and Indications",
     ["Liver biopsy indicated if: ferritin >1000 ng/mL, elevated LFTs, or to stage fibrosis",
      "Histology: Prussian blue stain (Perls' stain) shows blue hemosiderin in periportal hepatocytes",
      "HFE-related HH: iron gradient in hepatocytes (zone 1 > zone 3); spares Kupffer cells initially",
      "HIC (hepatic iron concentration): normal <1500 μg/g dry weight; symptomatic HH usually >10,000 μg/g",
      "Fibrosis/cirrhosis rarely seen until HIC >20,000 μg/g",
      "Hepatic iron index (HIC in μmol/g ÷ age): ≥1.9 supports HH; largely superseded by HFE testing"]),

    # 16
    ("Imaging in Hemochromatosis",
     ["MRI: most practical non-invasive method to quantify hepatic iron content",
      "T2* and T2 signal loss on MRI correlates with iron concentration (liver appears dark)",
      "CT: liver may show increased attenuation due to iron, but insensitive for mild overload",
      "Newer MRI techniques (R2*, R2 relaxometry) show improved sensitivity for quantification",
      "SQUID (superconducting quantum interference device): most accurate, but available only at research centres",
      "MRI can assess cardiac iron (T2*) to guide chelation urgency in juvenile/transfusion hemochromatosis"]),

    # 17
    ("Differential Diagnosis",
     ["Secondary iron overload: thalassemia major, sideroblastic anemia, aplastic anemia",
      "Parenteral iron overload: repeated transfusions → initial Kupffer cell deposition",
      "Alcohol-associated liver disease (ALD): elevated ferritin; rarely homozygous C282Y",
      "Non-alcoholic steatohepatitis (NASH): commonly mildly elevated ferritin",
      "Dysmettabolic iron overload syndrome (DIOS): insulin resistance + mild iron overload",
      "Distinguishing tool: HFE genotype + hepatic iron index; C282Y homozygosity confirms HH"]),

    # 18
    ("Complications — Cirrhosis & HCC",
     ["Cirrhosis develops if untreated; risk proportional to degree and duration of iron loading",
      "Risk factors for progression: coexistent alcohol use, viral hepatitis, NASH",
      "Cirrhosis risk greatly increased when HIC >20,000 μg/g dry weight",
      "HCC: most serious long-term complication; 200-fold elevated risk in cirrhotic HH",
      "HCC can occur even after successful iron depletion in established cirrhosis",
      "Surveillance: 6-monthly liver ultrasound + AFP in all HH patients with cirrhosis"]),

    # 19
    ("Complications — Cardiac",
     ["Cardiac iron deposition leads to dilated cardiomyopathy and restrictive physiology",
      "Arrhythmias (AF, heart block) and sudden cardiac death reported",
      "Cardiac disease is more prominent in juvenile HH (types 2A/2B) and transfusional overload",
      "Echocardiography and cardiac MRI (T2*) assess cardiac iron burden",
      "Iron removal via phlebotomy or chelation can reverse early cardiac dysfunction",
      "Heart failure from iron overload may improve significantly with prompt treatment"]),

    # 20
    ("Complications — Endocrine & Joint",
     ["Diabetes mellitus in ~65% of patients with cirrhotic HH; related to pancreatic iron deposition",
      "Hypogonadotropic hypogonadism: impotence, amenorrhea, loss of secondary sex characteristics",
      "Hypothyroidism and adrenal insufficiency occur less frequently",
      "Arthropathy: chondrocalcinosis of wrists and knees; calcium pyrophosphate crystals on X-ray",
      "Joint disease (especially MCP 2&3 involvement) may not reverse with iron depletion",
      "Osteoporosis from hypogonadism and liver disease contributes to morbidity"]),

    # 21
    ("Screening — Who to Test",
     ["Population screening not universally recommended due to low penetrance of C282Y",
      "Case-finding screening recommended: transferrin saturation + serum ferritin",
      "Indications: unexplained liver disease, fatigue, arthralgias, diabetes, hypogonadism",
      "First-degree relatives of proven C282Y homozygotes: offer HFE genotyping",
      "Cascade family screening cost-effective; siblings have 25% chance of homozygosity",
      "Early diagnosis and treatment (before cirrhosis) results in normal life expectancy"]),

    # 22
    ("Diagnostic Algorithm (Box 75.2 pathway)",
     ["Step 1: Fasting transferrin saturation ≥45% → proceed to HFE genotyping",
      "Step 2: C282Y homozygote → confirm iron overload with ferritin; treat if elevated",
      "Step 3: Ferritin >1000 ng/mL or elevated LFTs → liver biopsy to stage fibrosis",
      "Step 4: Non-C282Y genotypes with iron overload → evaluate for secondary causes",
      "Step 5: Negative HFE + high iron indices → consider TFR2, HJV, HAMP mutations",
      "Liver biopsy not required in C282Y homozygotes with ferritin <1000 ng/mL and normal LFTs"]),

    # 23
    ("Treatment — Phlebotomy",
     ["Therapeutic phlebotomy is first-line treatment for HFE-related HH",
      "Each 500 mL unit of whole blood removes ~200–250 mg of iron",
      "Induction phase: weekly (or twice-weekly) phlebotomy until ferritin <50 ng/mL",
      "C282Y homozygotes with 10–20 g excess iron require 40–80 units removed over months",
      "Maintenance phase: 2–4 phlebotomies/year to keep ferritin 50–100 ng/mL",
      "Proton pump inhibitor (PPI) reduces intestinal non-heme iron absorption and phlebotomy burden"]),

    # 24
    ("Treatment — Phlebotomy Monitoring",
     ["Monitor hemoglobin before each phlebotomy; withhold if Hgb <11 g/dL",
      "Serum ferritin measured every 10–12 units (initially) to track iron depletion",
      "Once target ferritin (<50 ng/mL) reached, check ferritin every 3 months",
      "Transferrin saturation should also normalize with successful iron depletion",
      "Older or anemic patients: reduce to 0.5 unit per week or every 2 weeks",
      "Well-tolerated and inexpensive; donated blood from non-hereditary HH may be used"]),

    # 25
    ("Treatment — Iron Chelation",
     ["Deferoxamine (DFO): IV/SC chelator; 20–50 mg/kg/day × 5 days/week via portable pump",
      "DFO indicated when phlebotomy not tolerated (anemia, cardiovascular compromise)",
      "Deferasirox (Exjade): oral, once-daily chelator; effective in HH",
      "Serious deferasirox side effects: hepatic failure, GI bleeding, renal injury",
      "Deferasirox expensive compared to phlebotomy; reserved for selected patients",
      "Chelation therapy preferred in transfusional iron overload (thalassemia, aplastic anemia)"]),

    # 26
    ("Treatment — Outcomes",
     ["Treatment before cirrhosis: normal life expectancy achievable",
      "Treatment after cirrhosis: HCC risk persists even after iron removal",
      "Hepatic fibrosis may improve or stabilize with iron depletion",
      "Diabetes rarely reverses but glucose control improves with treatment",
      "Cardiomyopathy can reverse with early, aggressive iron depletion",
      "Arthropathy and hypogonadism often do not improve significantly with phlebotomy"]),

    # 27
    ("Prognosis",
     ["Symptomatic HH: historical 10-year survival 18% (untreated) vs. normal (treated)",
      "Iron depletion before cirrhosis → survival equivalent to general population",
      "Cirrhosis + HH: 5-year mortality significantly higher; HCC main cause of death",
      "Non-cirrhotic HH with normal LFTs: excellent prognosis with phlebotomy",
      "HCC in HH does not respond well to HCC-specific therapies (sorafenib data limited)",
      "Liver transplantation for end-stage cirrhosis: outcomes generally good; HFE mutation persists"]),

    # 28
    ("Special Populations — Liver Transplantation",
     ["Liver transplantation (LT) is definitive treatment for end-stage HH cirrhosis",
      "Post-LT outcomes in HH are slightly worse than other indications due to cardiac/other comorbidities",
      "HFE mutation persists in donor liver; donor liver may eventually develop iron overload over decades",
      "Pre-LT cardiac evaluation essential: cardiac iron may not clear before transplant",
      "Iron overload in extrahepatic organs (heart, pancreas) is NOT corrected by liver transplant",
      "Post-LT phlebotomy or chelation may still be needed to manage extrahepatic iron"]),

    # 29
    ("Secondary Iron Overload — Key Points",
     ["Thalassemia major and sickle cell disease: transfusional iron overload most common cause",
      "Each unit of packed RBC contains ~200–250 mg iron; accumulates in RES first",
      "In transfusional overload, initial iron deposition is in Kupffer cells (unlike HH)",
      "Alcohol-associated liver disease: elevated ferritin; rarely a true HH phenotype",
      "Insulin resistance syndrome: mild serum ferritin elevation; normal or minimally elevated TS",
      "Porphyria cutanea tarda: associated with hepatic iron overload; phlebotomy improves PCT"]),

    # 30
    ("Summary & Key Take-Home Points",
     ["HFE-related HH (C282Y homozygote) is the most common hereditary metabolic liver disease",
      "Screen with fasting transferrin saturation ≥45% + serum ferritin; confirm with HFE genotyping",
      "Liver biopsy needed if ferritin >1000, elevated LFTs, or to stage fibrosis",
      "Therapeutic phlebotomy: standard treatment; removes 200–250 mg iron per unit",
      "Treatment before cirrhosis = normal life expectancy; HCC risk persists post-cirrhosis",
      "Family screening of first-degree relatives essential; early detection is life-saving"]),
]


# ─────────────────────────────────────────────
#  BUILD SLIDES
# ─────────────────────────────────────────────

# Slide 1 — Title
slide1 = prs.slides.add_slide(blank_layout)
bg = slide1.shapes.add_shape(1, 0, 0, prs.slide_width, prs.slide_height)
hex_fill(bg, DARK_BG)
bg.line.fill.background()

# Side accent panel
add_rect(slide1, 0, 0, 0.55, 7.5, ACCENT)

# Main title
add_textbox(slide1, "HEMOCHROMATOSIS",
            x=0.85, y=1.5, w=11.5, h=1.5,
            font_size=48, bold=True, color=ACCENT2,
            align=PP_ALIGN.LEFT)

# Subtitle
add_textbox(slide1,
            "Pathophysiology, Diagnosis & Management",
            x=0.85, y=3.1, w=11.0, h=0.8,
            font_size=24, bold=False, color=WHITE,
            align=PP_ALIGN.LEFT)

# Source
add_textbox(slide1,
            "Source: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, Chapter 75",
            x=0.85, y=4.2, w=11.0, h=0.5,
            font_size=15, italic=True, color=MID_GREY,
            align=PP_ALIGN.LEFT)

# Decorative line
add_rect(slide1, 0.85, 4.0, 10.0, 0.05, ACCENT2)

# Build content slides
for i, item in enumerate(slides_data):
    if item is None:
        continue
    title_text, bullets = item
    slide = prs.slides.add_slide(blank_layout)
    add_bullet_slide(slide, title_text, bullets)


# ─────────────────────────────────────────────
#  SAVE
# ─────────────────────────────────────────────
out_path = "/tmp/workspace/hemochromatosis-ppt/Hemochromatosis_Sleisenger_Fordtran.pptx"
buf = BytesIO()
prs.save(buf)
with open(out_path, "wb") as f:
    f.write(buf.getvalue())

print(f"Saved: {out_path}")
print(f"Total slides: {len(prs.slides)}")