The Glomerular Filtration Barrier + Glomerulonephropathies - USMLE Ultra-High Yield Notes

#!/usr/bin/env python3
"""
USMLE Quick-Reference PDF: Glomerular Filtration Barrier + Glomerulopathies
Uses ReportLab for full layout control.
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import mm, cm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether, PageBreak
)
from reportlab.platypus.flowables import Flowable
from reportlab.graphics.shapes import Drawing, Rect, String, Line, Polygon, Circle, Group
from reportlab.graphics import renderPDF
import io

# ── Colour palette ────────────────────────────────────────────────────────────
C_DARK_BLUE  = colors.HexColor("#1A3A5C")
C_MED_BLUE   = colors.HexColor("#2E6DA4")
C_LIGHT_BLUE = colors.HexColor("#D6E8F7")
C_TEAL       = colors.HexColor("#1B7F79")
C_LIGHT_TEAL = colors.HexColor("#D0EFED")
C_ORANGE     = colors.HexColor("#E07B39")
C_LIGHT_ORA  = colors.HexColor("#FDEBD8")
C_PURPLE     = colors.HexColor("#5B3A8A")
C_LIGHT_PUR  = colors.HexColor("#EDE5F5")
C_RED        = colors.HexColor("#C0392B")
C_LIGHT_RED  = colors.HexColor("#FADBD8")
C_GREEN      = colors.HexColor("#1E7D45")
C_LIGHT_GRN  = colors.HexColor("#D5F0E0")
C_GREY       = colors.HexColor("#5A5A5A")
C_LGREY      = colors.HexColor("#F2F2F2")
C_WHITE      = colors.white
C_BLACK      = colors.black
C_GOLD       = colors.HexColor("#D4A017")

W, H = A4  # 595.27 x 841.89 pt

# ── Styles ────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

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

TITLE = S("Title2",
    fontSize=22, leading=28, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_CENTER, spaceAfter=4)

SUBTITLE = S("Subtitle2",
    fontSize=10, leading=14, textColor=C_LIGHT_BLUE,
    fontName="Helvetica", alignment=TA_CENTER)

SEC_HEAD = S("SecHead",
    fontSize=13, leading=17, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_LEFT,
    leftIndent=6, spaceAfter=2, spaceBefore=6)

SUB_HEAD = S("SubHead",
    fontSize=10, leading=13, textColor=C_DARK_BLUE,
    fontName="Helvetica-Bold", spaceAfter=2, spaceBefore=4)

BODY = S("Body2",
    fontSize=8.5, leading=12, textColor=C_GREY,
    fontName="Helvetica", spaceAfter=2)

BODY_B = S("BodyBold",
    fontSize=8.5, leading=12, textColor=C_BLACK,
    fontName="Helvetica-Bold", spaceAfter=2)

SMALL = S("Small",
    fontSize=7.5, leading=10, textColor=C_GREY,
    fontName="Helvetica", spaceAfter=1)

CODE = S("Code2",
    fontSize=7.8, leading=11, textColor=C_DARK_BLUE,
    fontName="Courier", spaceAfter=1, leftIndent=6)

USMLE = S("USMLE",
    fontSize=8.5, leading=12, textColor=C_DARK_BLUE,
    fontName="Helvetica-BoldOblique", spaceAfter=2,
    leftIndent=4, borderPad=4)

TABLE_HEAD = S("TH",
    fontSize=8, leading=10, textColor=C_WHITE,
    fontName="Helvetica-Bold", alignment=TA_CENTER)

TABLE_CELL = S("TC",
    fontSize=7.5, leading=10, textColor=C_GREY,
    fontName="Helvetica", alignment=TA_CENTER)

TABLE_CELL_L = S("TCL",
    fontSize=7.5, leading=10, textColor=C_GREY,
    fontName="Helvetica", alignment=TA_LEFT)

TABLE_CELL_B = S("TCB",
    fontSize=7.5, leading=10, textColor=C_BLACK,
    fontName="Helvetica-Bold", alignment=TA_CENTER)

# ── Custom Flowables ───────────────────────────────────────────────────────────

class ColorBox(Flowable):
    """A coloured header band."""
    def __init__(self, text, bg, fg=C_WHITE, height=22, width=None, radius=4, style=None):
        Flowable.__init__(self)
        self.text = text
        self.bg = bg
        self.fg = fg
        self.bheight = height
        self._width = width
        self.radius = radius
        self.style = style or ParagraphStyle("cb",
            fontSize=11, fontName="Helvetica-Bold",
            textColor=fg, alignment=TA_LEFT, leading=14)

    def wrap(self, availW, availH):
        self.availW = self._width or availW
        return self.availW, self.bheight + 4

    def draw(self):
        c = self.canv
        c.setFillColor(self.bg)
        c.roundRect(0, 0, self.availW, self.bheight, self.radius, fill=1, stroke=0)
        c.setFillColor(self.fg)
        c.setFont(self.style.fontName, self.style.fontSize)
        c.drawString(8, (self.bheight - self.style.fontSize) / 2 + 2, self.text)


class FiltrationBarrierDiagram(Flowable):
    """ASCII-art style cross-section of the filtration barrier."""
    def __init__(self, w=510, h=230):
        Flowable.__init__(self)
        self._w = w
        self._h = h

    def wrap(self, aW, aH):
        return self._w, self._h

    def draw(self):
        c = self.canv
        w, h = self._w, self._h

        # Background
        c.setFillColor(C_LGREY)
        c.roundRect(0, 0, w, h, 6, fill=1, stroke=0)

        # ---- Layers (from top = Bowman's space, bottom = capillary lumen)
        # Zones: y positions (bottom of each layer)
        lumen_top    = 18
        endo_top     = lumen_top + 48
        gbm_top      = endo_top + 38
        podo_top     = gbm_top + 52
        bowman_top   = h - 12

        # Capillary Lumen (bottom)
        c.setFillColor(colors.HexColor("#AED6F1"))
        c.rect(30, lumen_top - 14, w - 60, 14, fill=1, stroke=0)
        c.setFont("Helvetica-Bold", 7.5)
        c.setFillColor(C_DARK_BLUE)
        c.drawCentredString(w/2, lumen_top - 11, "CAPILLARY LUMEN  (blood)")

        # ── Layer 1: Fenestrated Endothelium ──────────────────────────────
        c.setFillColor(colors.HexColor("#5DADE2"))
        c.rect(30, lumen_top, w - 60, endo_top - lumen_top, fill=1, stroke=0)
        # Draw fenestrations (small white ovals)
        import math
        for xi in range(55, w - 55, 38):
            c.setFillColor(C_WHITE)
            c.ellipse(xi - 7, lumen_top + 10, xi + 7, lumen_top + 28, fill=1, stroke=0)
        # Negative charge symbols
        c.setFillColor(colors.HexColor("#F5B7B1"))
        c.setFont("Helvetica-Bold", 9)
        for xi in range(46, w - 55, 38):
            c.setFillColor(colors.HexColor("#C0392B"))
            c.drawString(xi - 2, lumen_top + 32, "−")
        # Label on left
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 8)
        c.drawString(35, lumen_top + 19, "LAYER 1")
        c.setFont("Helvetica", 7.5)
        c.drawString(35, lumen_top + 9, "Fenestrated")

        # Right-side annotation
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 7.5)
        c.drawString(w - 155, lumen_top + 32, "• 70–100 nm pores")
        c.drawString(w - 155, lumen_top + 21, "• Glycocalyx (−ve charge)")
        c.drawString(w - 155, lumen_top + 10, "• Coarse size filter")

        # ── Layer 2: GBM ──────────────────────────────────────────────────
        c.setFillColor(colors.HexColor("#D4AC0D"))
        c.rect(30, endo_top, w - 60, gbm_top - endo_top, fill=1, stroke=0)
        # Texture lines
        c.setStrokeColor(colors.HexColor("#B7950B"))
        c.setLineWidth(0.4)
        for yi in range(endo_top + 4, gbm_top, 6):
            c.line(30, yi, w - 30, yi)
        c.setFillColor(C_WHITE)
        c.setFont("Helvetica-Bold", 8)
        c.drawString(35, endo_top + 18, "LAYER 2  –  GBM")
        c.setFont("Helvetica", 7)
        c.drawString(35, endo_top + 7, "250–400 nm thick")

        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 7.5)
        c.drawString(w - 210, endo_top + 28, "• Type IV collagen + Laminin 521")
        c.drawString(w - 210, endo_top + 17, "• Heparan sulfate (−ve charge)")
        c.drawString(w - 210, endo_top + 6, "• SIZE + CHARGE barrier → stops albumin")

        # ── Layer 3: Podocyte foot processes ──────────────────────────────
        c.setFillColor(colors.HexColor("#A9DFBF"))
        c.rect(30, gbm_top, w - 60, podo_top - gbm_top, fill=1, stroke=0)
        # Draw interdigitating foot process stumps
        fp_count = 10
        fp_w = (w - 100) / fp_count
        for i in range(fp_count):
            xi = 50 + i * fp_w
            # Alternating foot processes from 2 podocytes (different shade)
            shade = colors.HexColor("#27AE60") if i % 2 == 0 else colors.HexColor("#1E8449")
            c.setFillColor(shade)
            c.roundRect(xi, gbm_top + 6, fp_w * 0.55, podo_top - gbm_top - 10, 3, fill=1, stroke=0)
        # Slit diaphragm lines
        c.setStrokeColor(colors.HexColor("#922B21"))
        c.setLineWidth(1.2)
        for i in range(fp_count - 1):
            xi = 50 + i * fp_w + fp_w * 0.55
            mid_y = gbm_top + (podo_top - gbm_top) / 2 + 4
            c.line(xi, gbm_top + 8, xi + fp_w * 0.45, gbm_top + 8)

        c.setFillColor(colors.HexColor("#922B21"))
        c.setFont("Helvetica-Bold", 7)
        c.drawCentredString(w / 2 + 20, gbm_top + 1, "← slit diaphragms (nephrin / podocin) →")

        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 8)
        c.drawString(35, podo_top - 12, "LAYER 3  –  PODOCYTE")
        c.setFont("Helvetica", 7)
        c.drawString(35, podo_top - 22, "foot processes")

        c.setFont("Helvetica-Bold", 7.5)
        c.setFillColor(C_DARK_BLUE)
        c.drawString(w - 215, podo_top - 12, "• Interdigitating foot processes")
        c.drawString(w - 215, podo_top - 23, "• Slit diaphragm = nephrin, podocin, CD2AP")
        c.drawString(w - 215, podo_top - 34, "• FINAL and most specific barrier")
        c.drawString(w - 215, podo_top - 45, "• Effacement → proteinuria")

        # Bowman's space
        c.setFillColor(colors.HexColor("#EBF5FB"))
        c.rect(30, podo_top, w - 60, bowman_top - podo_top, fill=1, stroke=0)
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 7.5)
        c.drawCentredString(w / 2, podo_top + 5, "BOWMAN'S SPACE  (filtrate)")

        # Left border labels
        layer_labels = [
            (lumen_top + (endo_top - lumen_top)/2 + 2, "1"),
            (endo_top + (gbm_top - endo_top)/2,        "2"),
            (gbm_top + (podo_top - gbm_top)/2,         "3"),
        ]
        layer_cols = [C_MED_BLUE, colors.HexColor("#B7950B"), C_GREEN]
        for (ly, num), col in zip(layer_labels, layer_cols):
            c.setFillColor(col)
            c.circle(18, ly, 8, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 9)
            c.drawCentredString(18, ly - 3, num)

        # Title
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 9.5)
        c.drawCentredString(w / 2, h - 9, "GLOMERULAR FILTRATION BARRIER  —  Cross-Section")


class DepositLocationDiagram(Flowable):
    """Shows WHERE deposits sit relative to GBM for each disease."""
    def __init__(self, w=510, h=130):
        Flowable.__init__(self)
        self._w = w
        self._h = h

    def wrap(self, aW, aH):
        return self._w, self._h

    def draw(self):
        c = self.canv
        w, h = self._w, self._h

        # Background
        c.setFillColor(C_LGREY)
        c.roundRect(0, 0, w, h, 5, fill=1, stroke=0)

        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 9)
        c.drawCentredString(w/2, h - 12, "DEPOSIT LOCATION CHEAT SHEET")

        # Draw a capillary wall cross-section
        cx = 90   # centre x of the diagram
        top_y = h - 25
        bot_y = 22

        # Podocyte layer
        c.setFillColor(colors.HexColor("#A9DFBF"))
        c.rect(cx - 8, top_y - 15, 16, 15, fill=1, stroke=0)
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica", 7)
        c.drawCentredString(cx, top_y - 7, "POD")

        # GBM
        c.setFillColor(colors.HexColor("#F9E79F"))
        c.rect(cx - 8, bot_y + 25, 16, top_y - 15 - (bot_y + 25), fill=1, stroke=0)
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica-Bold", 7)
        c.drawCentredString(cx, (bot_y + 25 + top_y - 15) / 2 - 3, "GBM")

        # Endothelium
        c.setFillColor(colors.HexColor("#AED6F1"))
        c.rect(cx - 8, bot_y, 16, 25, fill=1, stroke=0)
        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica", 7)
        c.drawCentredString(cx, bot_y + 13, "END")

        c.setFillColor(C_DARK_BLUE)
        c.setFont("Helvetica", 6.5)
        c.drawCentredString(cx, bot_y - 10, "Lumen ↑")

        # Arrows + labels for each disease
        diseases = [
            # (x_offset, y_centre, colour, label, sublabel)
            (cx + 35, top_y - 8,   C_ORANGE,   "Membranous NP",    "subEPITHELIAL\n(spike & dome)"),
            (cx + 100, (bot_y + 25 + top_y - 15) / 2, C_PURPLE, "DDD / C3GN",  "intraMEMBRANOUS\n(dense ribbons)"),
            (cx + 170, bot_y + 13, C_RED,      "MPGN Type I",      "subENDOTHELIAL\n(tram-track)"),
            (cx + 240, (bot_y + 25 + top_y - 15) / 2 - 10, C_TEAL, "IgA / Mesangial", "MESANGIAL\n(IgA deposits)"),
        ]

        for dx, dy, col, label, sub in diseases:
            # Arrow from disease position to wall
            c.setStrokeColor(col)
            c.setLineWidth(1.5)
            c.line(cx + 10, dy, dx - 5, dy)
            # Arrow head
            c.setFillColor(col)
            c.polygon([dx - 5, dy + 4, dx - 5, dy - 4, dx + 2, dy], fill=1, stroke=0)
            # Dot on wall
            c.setFillColor(col)
            c.circle(cx + 10, dy, 4, fill=1, stroke=0)
            # Disease box
            c.setFillColor(col)
            bw = 100
            bh = 28
            c.roundRect(dx + 5, dy - bh/2, bw, bh, 3, fill=1, stroke=0)
            c.setFillColor(C_WHITE)
            c.setFont("Helvetica-Bold", 7)
            c.drawString(dx + 9, dy + 6, label)
            lines = sub.split("\n")
            c.setFont("Helvetica", 6.5)
            c.drawString(dx + 9, dy - 2, lines[0])
            if len(lines) > 1:
                c.drawString(dx + 9, dy - 10, lines[1])


# ── Helper: disease card ───────────────────────────────────────────────────────
def disease_card(title, color_bg, color_light, rows, usmle_line):
    """Returns a list of flowables for one disease section."""
    items = []
    items.append(ColorBox(title, color_bg, C_WHITE, height=20))
    items.append(Spacer(1, 3))

    for label, content in rows:
        row_data = [[
            Paragraph(f"<b>{label}</b>", TABLE_CELL_B),
            Paragraph(content, TABLE_CELL_L)
        ]]
        t = Table(row_data, colWidths=[85, W - 85 - 72])
        t.setStyle(TableStyle([
            ("BACKGROUND", (0, 0), (0, 0), color_light),
            ("BACKGROUND", (1, 0), (1, 0), C_WHITE),
            ("ALIGN",      (0, 0), (0, 0), "CENTER"),
            ("VALIGN",     (0, 0), (-1, -1), "MIDDLE"),
            ("GRID",       (0, 0), (-1, -1), 0.4, colors.HexColor("#CCCCCC")),
            ("TOPPADDING",    (0, 0), (-1, -1), 3),
            ("BOTTOMPADDING", (0, 0), (-1, -1), 3),
            ("LEFTPADDING",   (0, 0), (-1, -1), 5),
            ("RIGHTPADDING",  (0, 0), (-1, -1), 5),
        ]))
        items.append(t)

    items.append(Spacer(1, 3))
    # USMLE one-liner box
    usmle_data = [[
        Paragraph("USMLE ONE-LINER", TABLE_HEAD),
        Paragraph(usmle_line, USMLE)
    ]]
    ut = Table(usmle_data, colWidths=[90, W - 90 - 72])
    ut.setStyle(TableStyle([
        ("BACKGROUND",    (0, 0), (0, 0), color_bg),
        ("BACKGROUND",    (1, 0), (1, 0), color_light),
        ("VALIGN",        (0, 0), (-1, -1), "MIDDLE"),
        ("GRID",          (0, 0), (-1, -1), 0.5, color_bg),
        ("TOPPADDING",    (0, 0), (-1, -1), 4),
        ("BOTTOMPADDING", (0, 0), (-1, -1), 4),
        ("LEFTPADDING",   (0, 0), (-1, -1), 5),
    ]))
    items.append(ut)
    items.append(Spacer(1, 8))
    return items


# ── Build document ─────────────────────────────────────────────────────────────
OUT = "/home/daytona/workspace/glomerulo-pdf/Glomerular_Quick_Reference.pdf"

doc = SimpleDocTemplate(
    OUT,
    pagesize=A4,
    leftMargin=28, rightMargin=28,
    topMargin=22, bottomMargin=22,
    title="Glomerular Filtration Barrier & Glomerulopathies",
    author="Orris Medical AI",
)

story = []

# ══ HEADER BANNER ══════════════════════════════════════════════════════════════
header_data = [[
    Paragraph("GLOMERULAR FILTRATION BARRIER<br/><font size='11'>+ Glomerulopathies USMLE Quick Reference</font>", TITLE),
    Paragraph("Robbins Pathology · Brenner &amp; Rector · NKF Primer<br/>USMLE Step 1 / Step 2 CK", SUBTITLE),
]]
header_tbl = Table(header_data, colWidths=[W - 56])
header_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0, 0), (-1, -1), C_DARK_BLUE),
    ("ROUNDEDCORNERS", (0, 0), (-1, -1), [8, 8, 8, 8]),
    ("TOPPADDING",    (0, 0), (-1, -1), 10),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 10),
]))
story.append(header_tbl)
story.append(Spacer(1, 10))

# ══ SECTION 1: FILTRATION BARRIER ═════════════════════════════════════════════
story.append(ColorBox("  SECTION 1 — THE THREE-LAYER GLOMERULAR FILTRATION BARRIER", C_MED_BLUE, height=22))
story.append(Spacer(1, 6))
story.append(FiltrationBarrierDiagram(w=W - 56, h=215))
story.append(Spacer(1, 8))

# Layer table
layer_rows = [
    [Paragraph("Layer", TABLE_HEAD),
     Paragraph("Structure", TABLE_HEAD),
     Paragraph("Key Components", TABLE_HEAD),
     Paragraph("Barrier Function", TABLE_HEAD),
     Paragraph("Charge", TABLE_HEAD)],
    [Paragraph("1", TABLE_CELL_B),
     Paragraph("Fenestrated Endothelium", TABLE_CELL_L),
     Paragraph("70–100 nm fenestrae; glycocalyx coat", TABLE_CELL_L),
     Paragraph("Coarse size filter; excludes cells + large proteins", TABLE_CELL_L),
     Paragraph("Negative (heparan sulfate)", TABLE_CELL_L)],
    [Paragraph("2", TABLE_CELL_B),
     Paragraph("GBM (Glomerular Basement Membrane)", TABLE_CELL_L),
     Paragraph("Type IV collagen, laminin 521, heparan sulfate proteoglycans; 250–400 nm", TABLE_CELL_L),
     Paragraph("SIZE + CHARGE — main barrier to albumin (IgG-size molecules)", TABLE_CELL_L),
     Paragraph("Strongly negative", TABLE_CELL_L)],
    [Paragraph("3", TABLE_CELL_B),
     Paragraph("Podocyte Foot Processes + Slit Diaphragm", TABLE_CELL_L),
     Paragraph("Nephrin, podocin, CD2AP, α-actinin-4; slit 25–60 nm", TABLE_CELL_L),
     Paragraph("Final and most selective barrier; effacement → massive proteinuria", TABLE_CELL_L),
     Paragraph("Negative (podocalyxin)", TABLE_CELL_L)],
]

lt = Table(layer_rows, colWidths=[28, 100, 140, 155, 92])
lt.setStyle(TableStyle([
    ("BACKGROUND",    (0, 0), (-1, 0), C_DARK_BLUE),
    ("BACKGROUND",    (0, 1), (0, 1), colors.HexColor("#AED6F1")),
    ("BACKGROUND",    (0, 2), (0, 2), colors.HexColor("#F9E79F")),
    ("BACKGROUND",    (0, 3), (0, 3), colors.HexColor("#A9DFBF")),
    ("ROWBACKGROUNDS", (1, 1), (-1, -1), [C_WHITE, C_LGREY, C_WHITE]),
    ("GRID",          (0, 0), (-1, -1), 0.5, colors.HexColor("#AAAAAA")),
    ("VALIGN",        (0, 0), (-1, -1), "MIDDLE"),
    ("ALIGN",         (0, 0), (0, -1), "CENTER"),
    ("TOPPADDING",    (0, 0), (-1, -1), 3),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 3),
    ("LEFTPADDING",   (0, 0), (-1, -1), 4),
    ("RIGHTPADDING",  (0, 0), (-1, -1), 4),
]))
story.append(lt)
story.append(Spacer(1, 6))

# Mesangial cells note
meso = Table([[
    Paragraph("MESANGIAL CELLS", TABLE_HEAD),
    Paragraph(
        "NOT part of the filtration barrier. Sit between capillary loops. "
        "Provide structural support, phagocytose immune complexes, regulate GFR via contraction. "
        "<b>Proliferate in IgA nephropathy and MPGN.</b>",
        TABLE_CELL_L)
]], colWidths=[100, W - 56 - 100])
meso.setStyle(TableStyle([
    ("BACKGROUND",    (0, 0), (0, 0), C_TEAL),
    ("BACKGROUND",    (1, 0), (1, 0), C_LIGHT_TEAL),
    ("GRID",          (0, 0), (-1, -1), 0.5, C_TEAL),
    ("VALIGN",        (0, 0), (-1, -1), "MIDDLE"),
    ("TOPPADDING",    (0, 0), (-1, -1), 4),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 4),
    ("LEFTPADDING",   (0, 0), (-1, -1), 5),
]))
story.append(meso)
story.append(Spacer(1, 10))

# ══ EFFACEMENT TABLE ══════════════════════════════════════════════════════════
story.append(ColorBox("  FOOT PROCESS EFFACEMENT — KEY DISCRIMINATOR", C_TEAL, height=20))
story.append(Spacer(1, 4))

eff_rows = [
    [Paragraph("Finding on EM", TABLE_HEAD),
     Paragraph("Immune Deposits?", TABLE_HEAD),
     Paragraph("LM Finding", TABLE_HEAD),
     Paragraph("Disease", TABLE_HEAD)],
    [Paragraph("Diffuse effacement, NO deposits", TABLE_CELL_L),
     Paragraph("None", TABLE_CELL),
     Paragraph("Normal glomeruli", TABLE_CELL_L),
     Paragraph("Minimal Change Disease (MCD)", TABLE_CELL_B)],
    [Paragraph("Diffuse effacement + segmental sclerosis", TABLE_CELL_L),
     Paragraph("None", TABLE_CELL),
     Paragraph("Focal-segmental sclerosis/hyalinosis", TABLE_CELL_L),
     Paragraph("FSGS", TABLE_CELL_B)],
    [Paragraph("Subepithelial deposits (spike & dome)", TABLE_CELL_L),
     Paragraph("IgG4 + C3 (granular, along GBM)", TABLE_CELL),
     Paragraph("Diffuse capillary wall thickening", TABLE_CELL_L),
     Paragraph("Membranous Nephropathy", TABLE_CELL_B)],
    [Paragraph("Subendothelial deposits + tram-track", TABLE_CELL_L),
     Paragraph("IgG + C3 (Type I)\nC3 only (Type II/DDD)", TABLE_CELL),
     Paragraph("Lobular, hypercellular, split GBM", TABLE_CELL_L),
     Paragraph("MPGN", TABLE_CELL_B)],
    [Paragraph("Mesangial deposits", TABLE_CELL_L),
     Paragraph("IgA dominant", TABLE_CELL),
     Paragraph("Mesangial expansion", TABLE_CELL_L),
     Paragraph("IgA Nephropathy", TABLE_CELL_B)],
]
et = Table(eff_rows, colWidths=[155, 115, 140, 105])
et.setStyle(TableStyle([
    ("BACKGROUND",    (0, 0), (-1, 0), C_TEAL),
    ("ROWBACKGROUNDS", (0, 1), (-1, -1), [C_WHITE, C_LGREY]),
    ("GRID",          (0, 0), (-1, -1), 0.5, colors.HexColor("#AAAAAA")),
    ("VALIGN",        (0, 0), (-1, -1), "MIDDLE"),
    ("TOPPADDING",    (0, 0), (-1, -1), 3),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 3),
    ("LEFTPADDING",   (0, 0), (-1, -1), 4),
]))
story.append(et)
story.append(Spacer(1, 10))

# ══ DEPOSIT LOCATION DIAGRAM ══════════════════════════════════════════════════
story.append(ColorBox("  DEPOSIT LOCATION — WHERE IMMUNE COMPLEXES SIT", C_PURPLE, height=20))
story.append(Spacer(1, 5))
story.append(DepositLocationDiagram(w=W - 56, h=115))
story.append(Spacer(1, 10))

# ══ PAGE BREAK ════════════════════════════════════════════════════════════════
story.append(PageBreak())

# ══ SECTION 2 HEADER ══════════════════════════════════════════════════════════
story.append(ColorBox("  SECTION 2 — THREE GLOMERULOPATHIES (NEPHROTIC-PREDOMINANT)", C_MED_BLUE, height=22))
story.append(Spacer(1, 8))

# ── FSGS ──────────────────────────────────────────────────────────────────────
story += disease_card(
    "  1.  FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)",
    C_ORANGE, C_LIGHT_ORA,
    [
        ("Syndrome",       "NEPHROTIC — massive proteinuria (non-selective), edema, hypoalbuminemia, hyperlipidemia; + hematuria, HTN (more than MCD)"),
        ("Pathogenesis",   "<b>Podocyte loss exceeds compensation capacity.</b> Primary: circulating permeability factor (suPAR). Secondary: HIV (collapsing HIVAN), heroin, sickle cell, obesity. Genetic: APOL1 G1/G2 alleles (Black patients), nephrin/podocin/α-actinin-4 mutations."),
        ("Light Micro",    "Focal (&lt;50% glomeruli) + Segmental (part of tuft) sclerosis and hyalinosis. Rest of glomerulus and other glomeruli appear normal."),
        ("Electron Micro", "<b>Diffuse foot process effacement</b> — NO electron-dense immune deposits (unlike MN). Segmental collapse of capillary tuft."),
        ("Immuno-fluor.",  "<b>NEGATIVE</b> — no immune complex deposits. May see non-specific IgM/C3 in sclerotic segments."),
        ("Complement",     "Normal C3, C4."),
        ("Treatment",      "Steroids (poor response vs MCD). Cyclosporine, tacrolimus for steroid-resistant. ACE inhibitor for proteinuria."),
        ("Prognosis",      "Poor: 50% → ESKD in 10 years. Recurs in 25–50% of kidney transplants (circulating factor persists)."),
    ],
    "Black patient or HIV patient + steroid-resistant nephrotic syndrome + NO deposits on EM = FSGS. Ask about APOL1 alleles."
)

# ── MEMBRANOUS NEPHROPATHY ────────────────────────────────────────────────────
story += disease_card(
    "  2.  MEMBRANOUS NEPHROPATHY (MN)",
    C_PURPLE, C_LIGHT_PUR,
    [
        ("Syndrome",       "<b>NEPHROTIC — #1 cause of nephrotic syndrome in adults.</b> Proteinuria ± selective early. Insidious onset, no hematuria initially."),
        ("Pathogenesis",   "<b>Primary (75%):</b> IgG4 anti-PLA2R antibodies → bind PLA2R on podocyte basal surface → complement (MAC/C5b-9) activation → immune aggregates shed → lodge <b>subepithelially</b> → GBM grows spikes around deposits. Other antigens: NELL1, THSD7A, EXT1/2. <b>Secondary (25%):</b> Drugs (NSAIDs, penicillamine, gold), malignancy (lung, colon, melanoma), SLE (Class V), infections (HBV, HCV, syphilis)."),
        ("Light Micro",    "Diffuse thickening of capillary walls. Silver stain → <b>'spike and dome'</b> pattern (GBM spikes project up between subepithelial deposits)."),
        ("Electron Micro", "<b>Subepithelial electron-dense deposits</b> (between podocyte foot processes and GBM). Stage I→IV: deposits grow, GBM progressively encircles them."),
        ("Immuno-fluor.",  "Granular IgG (IgG4) + C3 along GBM. C1q + C4 may be present in secondary forms."),
        ("Complement",     "Normal serum C3/C4 in primary MN. May be low in SLE-associated."),
        ("Diagnosis",      "Anti-PLA2R antibody titre (serum) — positive in ~75% primary MN. Confirms diagnosis, monitors remission."),
        ("Prognosis",      "Rule of thirds: 1/3 spontaneous remission, 1/3 persistent stable, 1/3 → renal failure. Rituximab (anti-CD20) first-line for primary MN."),
    ],
    "Adult + nephrotic syndrome + spike-and-dome on silver stain + granular IgG on IF + subepithelial deposits on EM = Membranous NP. Rule out malignancy/SLE."
)

# ── MPGN ──────────────────────────────────────────────────────────────────────
story += disease_card(
    "  3.  MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)",
    C_RED, C_LIGHT_RED,
    [
        ("Syndrome",       "<b>MIXED NEPHROTIC + NEPHRITIC</b> — hematuria + proteinuria + HTN + edema. Low C3. Young adults/adolescents."),
        ("Classification", "<b>Type I (IC-MPGN):</b> Immune complex-mediated. Causes: HCV + cryoglobulinemia, HBV, SLE, endocarditis. Deposits: subendothelial + mesangial. Classical complement → C3 low AND C4 low. IF: IgG + C3 + C1q + C4.<br/><b>C3 Glomerulopathy (old Type II / DDD):</b> Alternative complement dysregulation. C3NeF autoantibody stabilises C3 convertase → uncontrolled C3 activation. Deposits: intramembranous dense ribbons (DDD). C3 very low, C4 NORMAL. IF: C3 only (no IgG, no C1q, no C4)."),
        ("Light Micro",    "Large, <b>lobular, hypercellular</b> glomeruli. <b>Tram-track / double-contour GBM</b> on PAS or silver stain (mesangial interposition between split GBMs). Endocapillary proliferation."),
        ("Electron Micro", "Type I: <b>Subendothelial</b> electron-dense deposits + mesangial deposits.<br/>Type II/DDD: <b>Intramembranous</b> ribbonlike, extremely electron-dense material permeating lamina densa."),
        ("Immuno-fluor.",  "Type I: IgG + C3 + C1q + C4 (granular). Type II/DDD: C3 only — no immunoglobulin, no C1q, no C4."),
        ("Complement KEY", "<b>Both types: Low C3.</b> C4 low in Type I (classical pathway used). C4 NORMAL in Type II/DDD (only alternative pathway)."),
        ("Secondary MPGN", "Chronic immune complex disorders: SLE, HCV, HBV, endocarditis, cryoglobulinemia. Malignancy with paraprotein. Always work up for underlying cause in adults."),
        ("Prognosis",      "Poor — 50% → chronic renal failure within 10 years. Treat underlying cause. No proven benefit of steroids/immunosuppressants in primary MPGN."),
    ],
    "HCV patient + mixed nephrotic-nephritic + LOW C3 + lobular glomeruli + tram-track = MPGN Type I. If C4 NORMAL with very low C3 → C3 glomerulopathy (DDD). Check for C3NeF."
)

# ══ MASTER COMPARISON TABLE ═══════════════════════════════════════════════════
story.append(ColorBox("  MASTER COMPARISON TABLE", C_DARK_BLUE, height=22))
story.append(Spacer(1, 5))

comp_rows = [
    [Paragraph(h, TABLE_HEAD) for h in
     ["", "MCD", "FSGS", "Membranous NP", "MPGN Type I", "MPGN / DDD (C3G)"]],
    [Paragraph("Syndrome", TABLE_CELL_B),
     Paragraph("Nephrotic", TABLE_CELL),
     Paragraph("Nephrotic", TABLE_CELL),
     Paragraph("Nephrotic", TABLE_CELL),
     Paragraph("Both", TABLE_CELL),
     Paragraph("Both", TABLE_CELL)],
    [Paragraph("Peak Age", TABLE_CELL_B),
     Paragraph("Children", TABLE_CELL),
     Paragraph("Adults (any)", TABLE_CELL),
     Paragraph("Adults 30–50", TABLE_CELL),
     Paragraph("Teens/YA", TABLE_CELL),
     Paragraph("Teens/YA", TABLE_CELL)],
    [Paragraph("LM", TABLE_CELL_B),
     Paragraph("Normal", TABLE_CELL),
     Paragraph("Focal-seg sclerosis", TABLE_CELL),
     Paragraph("Thick walls\n(spike & dome)", TABLE_CELL),
     Paragraph("Lobular, tram-track", TABLE_CELL),
     Paragraph("Lobular, tram-track; dense intramembranous", TABLE_CELL)],
    [Paragraph("EM Deposits", TABLE_CELL_B),
     Paragraph("None\n(diffuse effacement)", TABLE_CELL),
     Paragraph("None\n(effacement + sclerosis)", TABLE_CELL),
     Paragraph("Subepithelial", TABLE_CELL),
     Paragraph("Subendothelial\n+ mesangial", TABLE_CELL),
     Paragraph("Intramembranous\n(dense ribbons)", TABLE_CELL)],
    [Paragraph("IF Pattern", TABLE_CELL_B),
     Paragraph("Negative", TABLE_CELL),
     Paragraph("Negative", TABLE_CELL),
     Paragraph("Granular IgG4\n+ C3 (GBM)", TABLE_CELL),
     Paragraph("IgG + C3\n+ C1q + C4", TABLE_CELL),
     Paragraph("C3 ONLY\n(no IgG/C1q/C4)", TABLE_CELL)],
    [Paragraph("C3 / C4", TABLE_CELL_B),
     Paragraph("Normal", TABLE_CELL),
     Paragraph("Normal", TABLE_CELL),
     Paragraph("Normal", TABLE_CELL),
     Paragraph("C3↓ C4↓", TABLE_CELL),
     Paragraph("C3↓↓ C4 Normal", TABLE_CELL)],
    [Paragraph("Key Antigen / Cause", TABLE_CELL_B),
     Paragraph("Unknown\n(permeability factor)", TABLE_CELL),
     Paragraph("suPAR, APOL1\nHIV, podocin", TABLE_CELL),
     Paragraph("Anti-PLA2R\n(IgG4) – 75%", TABLE_CELL),
     Paragraph("HCV, SLE\nHBV, endocarditis", TABLE_CELL),
     Paragraph("C3NeF autoAb\nFactor H mutation", TABLE_CELL)],
    [Paragraph("Steroid Resp.", TABLE_CELL_B),
     Paragraph("Excellent ✓", TABLE_CELL),
     Paragraph("Poor ✗", TABLE_CELL),
     Paragraph("Partial (Rituximab)", TABLE_CELL),
     Paragraph("None", TABLE_CELL),
     Paragraph("None", TABLE_CELL)],
    [Paragraph("Prognosis", TABLE_CELL_B),
     Paragraph("Good (90% remit)", TABLE_CELL),
     Paragraph("50% ESKD/10yr\nRecurs in Tx", TABLE_CELL),
     Paragraph("Rule of 1/3s", TABLE_CELL),
     Paragraph("50% CRF/10yr", TABLE_CELL),
     Paragraph("50% CRF/10yr", TABLE_CELL)],
]

ct = Table(comp_rows, colWidths=[75, 82, 88, 92, 87, 95])
comp_style = TableStyle([
    ("BACKGROUND",    (0, 0), (-1, 0), C_DARK_BLUE),
    ("BACKGROUND",    (0, 1), (0, -1), C_LIGHT_BLUE),
    ("ROWBACKGROUNDS", (1, 1), (-1, -1), [C_WHITE, C_LGREY]),
    ("GRID",          (0, 0), (-1, -1), 0.4, colors.HexColor("#BBBBBB")),
    ("VALIGN",        (0, 0), (-1, -1), "MIDDLE"),
    ("ALIGN",         (1, 0), (-1, -1), "CENTER"),
    ("TOPPADDING",    (0, 0), (-1, -1), 3),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 3),
    ("LEFTPADDING",   (0, 0), (-1, -1), 3),
    ("RIGHTPADDING",  (0, 0), (-1, -1), 3),
    # Highlight FSGS row
    ("BACKGROUND",    (2, 1), (2, -1), colors.HexColor("#FEF9E7")),
    # Highlight MN
    ("BACKGROUND",    (3, 1), (3, -1), colors.HexColor("#F5EEF8")),
    # Highlight MPGN
    ("BACKGROUND",    (4, 1), (4, -1), colors.HexColor("#FDEDEC")),
    ("BACKGROUND",    (5, 1), (5, -1), colors.HexColor("#FDEDEC")),
])
ct.setStyle(comp_style)
story.append(ct)
story.append(Spacer(1, 8))

# ══ FOOTER NOTE ═══════════════════════════════════════════════════════════════
footer_txt = (
    "<b>Sources:</b> Robbins, Cotran &amp; Kumar Pathologic Basis of Disease (10e) · "
    "Brenner &amp; Rector's The Kidney (11e) · "
    "National Kidney Foundation Primer on Kidney Diseases (8e) · "
    "Smith &amp; Tanagho's General Urology (19e)   |   "
    "<b>Generated by Orris Medical AI</b>"
)
story.append(Paragraph(footer_txt, SMALL))

# ── Build ──────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF saved to: {OUT}")

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/glomerulo-pdf/make_pdf.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/glomerulo-pdf/make_pdf.py'