Proteus mirabilis swarming motility mechanism flagella differentiation

alcohol induced acute pancreatitis pathophysiology mechanism 2024

ls /home/daytona/workspace/ 2>/dev/null && mkdir -p /home/daytona/workspace/rena…

~/renal-physiology-guide/create_pdf.py

#!/usr/bin/env python3
"""
Comprehensive Renal Physiology Study Guide PDF
Generated with ReportLab
"""

import json, subprocess, base64, os
from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, Image, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus.flowables import HRFlowable
from reportlab.graphics.shapes import Drawing, Rect, String, Line, Arrow, Polygon, Circle
from reportlab.graphics import renderPDF
from reportlab.graphics.shapes import Drawing, Rect, String, Line, Group
from io import BytesIO

# ─────────────────────────────────────────────────────────
# Colour Palette
# ─────────────────────────────────────────────────────────
NAVY      = colors.HexColor("#1a3a5c")
TEAL      = colors.HexColor("#2980b9")
LIGHT_BLUE= colors.HexColor("#d6eaf8")
GOLD      = colors.HexColor("#f39c12")
ORANGE    = colors.HexColor("#e67e22")
GREEN     = colors.HexColor("#27ae60")
LIGHT_GREEN = colors.HexColor("#d5f5e3")
RED       = colors.HexColor("#c0392b")
LIGHT_RED = colors.HexColor("#fadbd8")
PURPLE    = colors.HexColor("#8e44ad")
LIGHT_PURPLE = colors.HexColor("#e8daef")
GRAY      = colors.HexColor("#7f8c8d")
LIGHT_GRAY= colors.HexColor("#f2f3f4")
WHITE     = colors.white
DARK      = colors.HexColor("#2c3e50")

# ─────────────────────────────────────────────────────────
# Page setup
# ─────────────────────────────────────────────────────────
OUTPUT = "/home/daytona/workspace/renal-physiology-guide/Renal_Physiology_Study_Guide.pdf"
PAGE_W, PAGE_H = A4
MARGIN = 2 * cm

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=MARGIN, rightMargin=MARGIN,
    topMargin=2.2*cm, bottomMargin=2*cm,
    title="Renal Physiology – Comprehensive Study Guide",
    author="Orris Medical Education",
    subject="Renal Physiology"
)

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

def make_style(name, parent="Normal", **kwargs):
    return ParagraphStyle(name, parent=styles[parent], **kwargs)

ST_TITLE    = make_style("MyTitle",    "Title",   fontSize=26, textColor=NAVY,
                          spaceAfter=6, leading=32, alignment=TA_CENTER)
ST_SUBTITLE = make_style("MySubtitle","Normal",   fontSize=13, textColor=TEAL,
                          spaceAfter=4, alignment=TA_CENTER, italic=True)
ST_H1       = make_style("H1",        "Heading1", fontSize=15, textColor=WHITE,
                          spaceAfter=6, spaceBefore=14, leading=18)
ST_H2       = make_style("H2",        "Heading2", fontSize=12, textColor=NAVY,
                          spaceAfter=4, spaceBefore=10, leading=15)
ST_H3       = make_style("H3",        "Heading3", fontSize=10.5, textColor=TEAL,
                          spaceAfter=3, spaceBefore=6, leading=13)
ST_BODY     = make_style("Body",      "Normal",   fontSize=9.5, leading=14,
                          spaceAfter=4, alignment=TA_JUSTIFY)
ST_BULLET   = make_style("Bullet",    "Normal",   fontSize=9.5, leading=13,
                          spaceAfter=2, leftIndent=14, bulletIndent=4)
ST_BOX      = make_style("Box",       "Normal",   fontSize=9, leading=13,
                          spaceAfter=2, leftIndent=6, textColor=DARK)
ST_CAPTION  = make_style("Caption",   "Normal",   fontSize=8.5, italic=True,
                          textColor=GRAY, alignment=TA_CENTER, spaceAfter=4)
ST_KEY      = make_style("Key",       "Normal",   fontSize=9.5, textColor=RED,
                          leading=13, spaceAfter=2, leftIndent=14,
                          fontName="Helvetica-Bold")
ST_FORMULA  = make_style("Formula",   "Normal",   fontSize=10,
                          textColor=NAVY, fontName="Helvetica-Bold",
                          alignment=TA_CENTER, spaceAfter=6, spaceBefore=4)

# ─────────────────────────────────────────────────────────
# Helper: section header with coloured band
# ─────────────────────────────────────────────────────────
def section_header(text, color=NAVY, num=""):
    label = f"{num}  {text}" if num else text
    p = Paragraph(f"<font color='white'><b>{label}</b></font>", ST_H1)
    t = Table([[p]], colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",  (0,0), (-1,-1), 6),
        ("BOTTOMPADDING",(0,0),(-1,-1), 6),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def sub_header(text, color=TEAL):
    p = Paragraph(f"<b>{text}</b>", ST_H2)
    return p

def key_point(text):
    return Paragraph(f"<b>&#9733;</b>  {text}", ST_KEY)

def bullet(text, indent=0):
    style = ParagraphStyle("bul", parent=ST_BULLET, leftIndent=14+indent*12)
    return Paragraph(f"&#8226;  {text}", style)

def body(text):
    return Paragraph(text, ST_BODY)

def formula(text):
    return Paragraph(text, ST_FORMULA)

def spacer(h=0.3):
    return Spacer(1, h*cm)

def hr(color=TEAL, thickness=0.5):
    return HRFlowable(width="100%", thickness=thickness, color=color, spaceAfter=4, spaceBefore=4)

# ─────────────────────────────────────────────────────────
# Helper: styled table
# ─────────────────────────────────────────────────────────
def make_table(header, rows, col_widths=None, header_color=NAVY, alt_color=LIGHT_BLUE):
    data = [[Paragraph(f"<b><font color='white'>{h}</font></b>", ST_BOX) for h in header]]
    for i, row in enumerate(rows):
        data.append([Paragraph(str(c), ST_BOX) for c in row])

    if col_widths is None:
        avail = PAGE_W - 2*MARGIN
        col_widths = [avail / len(header)] * len(header)

    t = Table(data, colWidths=col_widths, repeatRows=1)
    style = [
        ("BACKGROUND", (0,0), (-1,0), header_color),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, alt_color]),
        ("GRID", (0,0), (-1,-1), 0.4, colors.HexColor("#bdc3c7")),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ]
    t.setStyle(TableStyle(style))
    return t

# ─────────────────────────────────────────────────────────
# Helper: info box
# ─────────────────────────────────────────────────────────
def info_box(title, lines, bg=LIGHT_BLUE, border=TEAL):
    content = [Paragraph(f"<b>{title}</b>", ST_H3)]
    for l in lines:
        content.append(Paragraph(f"&#8226;  {l}", ST_BOX))
    t = Table([[content]], colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX", (0,0), (-1,-1), 1.5, border),
        ("TOPPADDING",  (0,0), (-1,-1), 8),
        ("BOTTOMPADDING",(0,0),(-1,-1), 8),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
        ("RIGHTPADDING",(0,0), (-1,-1), 10),
    ]))
    return t

# ─────────────────────────────────────────────────────────
# Diagram helpers (pure ReportLab Drawing objects)
# ─────────────────────────────────────────────────────────
def nephron_flow_diagram():
    """Simple flow diagram of nephron segments"""
    d = Drawing(480, 200)
    segments = [
        ("Bowman's\nCapsule", 0,   TEAL,  "300 mOsm"),
        ("PCT",               90,  GREEN, "~300 mOsm\n65% reabs."),
        ("Loop of\nHenle",   180,  ORANGE,"100 mOsm\n(exit)"),
        ("DCT",              270,  PURPLE,"~100 mOsm"),
        ("Collecting\nDuct", 360,  RED,   "50-1400\nmOsm"),
    ]
    for (label, x, col, osm) in segments:
        # box
        d.add(Rect(x+2, 60, 78, 70, fillColor=col, strokeColor=WHITE, strokeWidth=1.5, rx=6, ry=6))
        # label
        for i, line in enumerate(label.split("\n")):
            d.add(String(x+41, 115 - i*12, line, fontSize=8, fillColor=WHITE,
                         textAnchor="middle", fontName="Helvetica-Bold"))
        # osmolarity below
        for i, line in enumerate(osm.split("\n")):
            d.add(String(x+41, 52 - i*11, line, fontSize=7.5, fillColor=col,
                         textAnchor="middle"))
        # arrow between boxes
        if x < 360:
            d.add(Line(x+82, 95, x+90, 95, strokeColor=GRAY, strokeWidth=1.5))
            d.add(Polygon([x+88, 99, x+88, 91, x+94, 95], fillColor=GRAY, strokeColor=GRAY))

    # Labels at top
    d.add(String(240, 185, "Nephron Segment Flow & Osmolarity",
                 fontSize=11, textAnchor="middle", fontName="Helvetica-Bold", fillColor=NAVY))
    d.add(String(240, 170, "(Numbers = approximate tubular fluid osmolarity)",
                 fontSize=8, textAnchor="middle", fillColor=GRAY))
    return d


def starling_forces_diagram():
    """Starling forces at the glomerulus"""
    d = Drawing(480, 160)
    # Glomerulus circle
    d.add(Circle(120, 80, 55, fillColor=colors.HexColor("#f5cba7"),
                 strokeColor=ORANGE, strokeWidth=2))
    d.add(String(120, 78, "Glomerular", fontSize=9, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=DARK))
    d.add(String(120, 66, "Capillary", fontSize=9, textAnchor="middle", fillColor=DARK))

    # Forces arrows and labels
    forces = [
        # (x1,y1,x2,y2, label, value, color, direction)
        (180, 80, 300, 80, "Pgc (hydrostatic)", "60 mmHg", GREEN, "→ promotes"),
        (120, 140, 120, 170, "Pbs (capsule P)", "18 mmHg", RED, "↑ opposes"),
        (60,  80, -30, 80, "πgc (oncotic)", "32 mmHg", PURPLE, "← opposes"),
    ]
    # Net
    d.add(Rect(310, 50, 160, 65, fillColor=LIGHT_GREEN, strokeColor=GREEN, strokeWidth=1.5, rx=4, ry=4))
    d.add(String(390, 105, "NET FILTRATION", fontSize=9, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=GREEN))
    d.add(String(390, 91, "PRESSURE", fontSize=9, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=GREEN))
    d.add(String(390, 77, "60 - 18 - 32", fontSize=10, textAnchor="middle", fillColor=DARK))
    d.add(String(390, 63, "= ~10 mmHg", fontSize=11, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=NAVY))

    # Force labels on left
    labels = [
        (10, 148, "Pgc = 60 mmHg  (promotes filtration)", GREEN),
        (10, 134, "Pbs = 18 mmHg  (opposes filtration)", RED),
        (10, 120, "pgc = 32 mmHg  (opposes filtration)", PURPLE),
    ]
    for (x, y, txt, col) in labels:
        d.add(String(x, y, txt, fontSize=8, fillColor=col))

    d.add(String(240, 10, "Starling Forces at the Glomerulus",
                 fontSize=10, textAnchor="middle", fontName="Helvetica-Bold", fillColor=NAVY))
    return d


def countercurrent_diagram():
    """Simplified countercurrent multiplier"""
    d = Drawing(480, 230)
    d.add(String(240, 218, "Countercurrent Multiplier – Osmolarity Gradient",
                 fontSize=10, textAnchor="middle", fontName="Helvetica-Bold", fillColor=NAVY))

    # Cortex / Medulla labels
    d.add(Rect(0, 150, 480, 60, fillColor=colors.HexColor("#fef9e7"),
               strokeColor=GOLD, strokeWidth=1))
    d.add(String(10, 192, "CORTEX", fontSize=9, fontName="Helvetica-Bold", fillColor=GOLD))

    d.add(Rect(0, 0, 480, 150, fillColor=colors.HexColor("#eaf2ff"),
               strokeColor=TEAL, strokeWidth=1))
    d.add(String(10, 8, "MEDULLA (inner)", fontSize=9, fontName="Helvetica-Bold", fillColor=TEAL))

    # Descending limb (left column, water permeable)
    dl_x = 120
    d.add(Rect(dl_x, 10, 50, 195, fillColor=colors.HexColor("#aed6f1"),
               strokeColor=TEAL, strokeWidth=1.5))
    d.add(String(dl_x+25, 205, "DESC.", fontSize=8, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=TEAL))
    d.add(String(dl_x+25, 195, "LIMB", fontSize=8, textAnchor="middle", fillColor=TEAL))
    # osmolarity values descending
    osm_vals = [(190, "300"), (160, "600"), (130, "900"), (100, "1200"), (70, "1200")]
    for (y, val) in osm_vals:
        d.add(String(dl_x+25, y, val, fontSize=8, textAnchor="middle", fillColor=NAVY))

    # Ascending limb (right column, impermeable to water)
    al_x = 200
    d.add(Rect(al_x, 10, 50, 195, fillColor=colors.HexColor("#a9dfbf"),
               strokeColor=GREEN, strokeWidth=1.5))
    d.add(String(al_x+25, 205, "ASC.", fontSize=8, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=GREEN))
    d.add(String(al_x+25, 195, "LIMB", fontSize=8, textAnchor="middle", fillColor=GREEN))
    osm_asc = [(185, "100"), (158, "300"), (128, "600"), (98, "900"), (68, "1200")]
    for (y, val) in osm_asc:
        d.add(String(al_x+25, y, val, fontSize=8, textAnchor="middle", fillColor=DARK))
    d.add(String(al_x+25, 45, "Active NaCl", fontSize=7, textAnchor="middle", fillColor=GREEN))
    d.add(String(al_x+25, 35, "pump (NKCC2)", fontSize=7, textAnchor="middle", fillColor=GREEN))
    d.add(String(al_x+25, 25, "NO water", fontSize=7, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=RED))

    # Collecting duct
    cd_x = 300
    d.add(Rect(cd_x, 10, 50, 195, fillColor=colors.HexColor("#f9ebea"),
               strokeColor=RED, strokeWidth=1.5))
    d.add(String(cd_x+25, 205, "COLL.", fontSize=8, textAnchor="middle",
                 fontName="Helvetica-Bold", fillColor=RED))
    d.add(String(cd_x+25, 195, "DUCT", fontSize=8, textAnchor="middle", fillColor=RED))
    for (y, val) in [(185,"1200"),(130,"ADH→"), (110,"water"), (90,"leaves")]:
        d.add(String(cd_x+25, y, val, fontSize=8, textAnchor="middle", fillColor=RED))

    # Medullary gradient arrow
    d.add(String(400, 190, "300", fontSize=9, fillColor=NAVY, fontName="Helvetica-Bold"))
    d.add(String(400, 100, "900", fontSize=9, fillColor=NAVY, fontName="Helvetica-Bold"))
    d.add(String(400, 20,  "1200", fontSize=9, fillColor=NAVY, fontName="Helvetica-Bold"))
    d.add(Line(420, 185, 420, 25, strokeColor=NAVY, strokeWidth=2))
    d.add(Polygon([416,25, 424,25, 420,15], fillColor=NAVY, strokeColor=NAVY))
    d.add(String(435, 100, "mOsm/L\ngradient", fontSize=8, fillColor=NAVY))

    return d


def raas_diagram():
    """RAAS cascade"""
    d = Drawing(480, 200)
    d.add(String(240, 190, "Renin-Angiotensin-Aldosterone System (RAAS)",
                 fontSize=10, textAnchor="middle", fontName="Helvetica-Bold", fillColor=NAVY))

    steps = [
        ("Low BP / Low Na+\nSymp. activity",  20,  130, TEAL),
        ("RENIN\n(JG cells)",                  110, 130, NAVY),
        ("Angiotensin I",                       200, 130, GRAY),
        ("Angiotensin II\n(ACE, lung)",         290, 130, ORANGE),
        ("ALDOSTERONE\n(adrenal cortex)",       380, 130, RED),
    ]

    for i, (label, x, y, col) in enumerate(steps):
        lines = label.split("\n")
        box_h = 12 * len(lines) + 14
        d.add(Rect(x, y - box_h//2, 82, box_h,
                   fillColor=col, strokeColor=WHITE, strokeWidth=1, rx=4, ry=4))
        for j, ln in enumerate(lines):
            d.add(String(x+41, y + (len(lines)-1)*6 - j*12,
                         ln, fontSize=7.5, textAnchor="middle",
                         fillColor=WHITE, fontName="Helvetica-Bold"))
        if i < len(steps)-1:
            d.add(Line(x+84, y, x+92, y, strokeColor=GRAY, strokeWidth=1.5))
            d.add(Polygon([x+90, y+3, x+90, y-3, x+96, y],
                          fillColor=GRAY, strokeColor=GRAY))

    # Effects of Ang II and Aldosterone
    d.add(Rect(200, 30, 170, 60, fillColor=LIGHT_GREEN, strokeColor=GREEN, strokeWidth=1, rx=4))
    effects = ["Na+ reabsorption (PCT, CD)",
               "K+ secretion (CD)",
               "Blood volume & BP"]
    d.add(String(285, 87, "NET EFFECTS:", fontSize=8,
                 textAnchor="middle", fontName="Helvetica-Bold", fillColor=GREEN))
    for i, e in enumerate(effects):
        d.add(String(285, 75 - i*11, f"+ {e}", fontSize=7.5,
                     textAnchor="middle", fillColor=DARK))

    return d


# ─────────────────────────────────────────────────────────
# Build PDF content
# ─────────────────────────────────────────────────────────
story = []

# ══════════════════════ COVER PAGE ══════════════════════
story.append(spacer(2))
# Coloured banner
banner = Table([[Paragraph("<font color='white'><b>RENAL PHYSIOLOGY</b></font>",
                            ParagraphStyle("bn", fontSize=30, alignment=TA_CENTER, leading=36))]],
               colWidths=[PAGE_W - 2*MARGIN])
banner.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), NAVY),
    ("TOPPADDING", (0,0), (-1,-1), 22),
    ("BOTTOMPADDING", (0,0), (-1,-1), 22),
    ("ROUNDEDCORNERS", [8]),
]))
story.append(banner)
story.append(spacer(0.4))
story.append(Paragraph("Comprehensive Study Guide", ST_SUBTITLE))
story.append(Paragraph("Based on Guyton &amp; Hall | Ganong's | Costanzo Physiology", ST_SUBTITLE))
story.append(spacer(0.6))

toc_items = [
    ("1", "Functional Anatomy of the Nephron"),
    ("2", "Glomerular Filtration &amp; GFR"),
    ("3", "Tubular Reabsorption &amp; Secretion"),
    ("4", "Loop of Henle &amp; Countercurrent Mechanism"),
    ("5", "Urine Concentration &amp; Dilution (ADH)"),
    ("6", "Hormonal Regulation (RAAS, ANP, PTH)"),
    ("7", "Renal Handling of Key Substances"),
    ("8", "Acid–Base Balance"),
    ("9", "Renal Clearance"),
    ("10", "Quick-Reference Tables &amp; Key Values"),
]
toc_data = [[Paragraph(f"<b>{n}.</b>  {t}", ST_BODY)] for n, t in toc_items]
toc_table = Table(toc_data, colWidths=[PAGE_W - 2*MARGIN])
toc_table.setStyle(TableStyle([
    ("ROWBACKGROUNDS", (0,0), (-1,-1), [WHITE, LIGHT_BLUE]),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 14),
    ("BOX", (0,0), (-1,-1), 1, TEAL),
]))
story.append(Paragraph("<b>Contents</b>", ST_H2))
story.append(toc_table)
story.append(spacer(1))

source_box = Table([[Paragraph(
    "<b>Primary Sources:</b>  Guyton &amp; Hall Textbook of Medical Physiology 14E  •  "
    "Ganong's Review of Medical Physiology 26E  •  Costanzo Physiology 7E  •  "
    "Brenner &amp; Rector's The Kidney",
    ParagraphStyle("src", fontSize=8.5, textColor=GRAY, alignment=TA_CENTER)
)]], colWidths=[PAGE_W - 2*MARGIN])
source_box.setStyle(TableStyle([
    ("BOX", (0,0), (-1,-1), 0.5, GRAY),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
]))
story.append(source_box)
story.append(PageBreak())

# ══════════════════════ SECTION 1: ANATOMY ══════════════════════
story.append(section_header("1.  Functional Anatomy of the Nephron", NAVY, ""))
story.append(spacer(0.3))
story.append(body(
    "Each kidney contains approximately <b>1 million nephrons</b>. The nephron is the "
    "functional unit of the kidney. Each nephron consists of a renal corpuscle (glomerulus + "
    "Bowman's capsule) and a renal tubule. The tubule drains sequentially through the "
    "proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and "
    "collecting duct system."
))
story.append(spacer(0.2))

story.append(sub_header("Types of Nephrons"))
story.append(make_table(
    ["Type", "Location", "Loop of Henle", "Key Role"],
    [
        ["Cortical nephrons (~75%)",
         "Outer cortex", "Short; barely enters medulla",
         "General filtration; isoosmotic reabsorption"],
        ["Juxtamedullary nephrons (~25%)",
         "Near corticomedullary junction", "Long; extends deep into medulla",
         "Urine concentration via countercurrent mechanism"],
    ],
    col_widths=[3.5*cm, 3.5*cm, 5*cm, 5.5*cm]
))
story.append(spacer(0.3))

story.append(sub_header("Blood Supply – The Two-Capillary-Bed System"))
story.append(body(
    "Renal artery → interlobar arteries → arcuate arteries → interlobular arteries → "
    "<b>afferent arteriole</b> → <b>glomerular capillaries</b> (high-pressure, filtration) → "
    "<b>efferent arteriole</b> → <b>peritubular capillaries / vasa recta</b> (low-pressure, "
    "reabsorption) → renal vein."
))
story.append(info_box("Why Two Capillary Beds Matter", [
    "Glomerular capillaries: high hydrostatic pressure (~60 mmHg) drives filtration",
    "Efferent arteriole resistance: fine-tunes GFR and peritubular reabsorption",
    "Peritubular capillaries: low pressure + high oncotic pressure drives reabsorption",
    "Vasa recta: countercurrent exchanger preserving medullary osmotic gradient",
], bg=LIGHT_BLUE, border=TEAL))
story.append(spacer(0.3))

story.append(sub_header("Nephron Flow Diagram"))
story.append(nephron_flow_diagram())
story.append(Paragraph(
    "Fig 1. Simplified nephron segments with approximate tubular fluid osmolarity at each stage",
    ST_CAPTION
))
story.append(PageBreak())

# ══════════════════════ SECTION 2: GFR ══════════════════════
story.append(section_header("2.  Glomerular Filtration &amp; GFR", TEAL, ""))
story.append(spacer(0.2))
story.append(key_point("Normal GFR = 125 mL/min = 180 L/day filtered. Only ~1.5 L excreted as urine – >99% reabsorbed!"))
story.append(spacer(0.2))

story.append(sub_header("The Filtration Barrier"))
story.append(body(
    "The glomerular filtration barrier has three layers: <b>(1)</b> fenestrated capillary "
    "endothelium (prevents cells), <b>(2)</b> glomerular basement membrane (GBM, blocks large "
    "proteins), <b>(3)</b> podocytes with slit diaphragms (prevents albumin). Substances "
    "freely filtered: electrolytes, glucose, urea, creatinine, amino acids. Proteins and "
    "protein-bound molecules are retained."
))
story.append(spacer(0.2))

story.append(sub_header("Starling Forces – Net Filtration Pressure"))
story.append(starling_forces_diagram())
story.append(Paragraph("Fig 2. Starling forces governing net glomerular filtration pressure (~10 mmHg)", ST_CAPTION))
story.append(spacer(0.2))

story.append(make_table(
    ["Force", "Value", "Direction", "Altered by"],
    [
        ["Glomerular capillary hydrostatic pressure (Pgc)", "~60 mmHg",
         "Promotes filtration", "Afferent/efferent arteriole tone, BP"],
        ["Bowman's capsule hydrostatic pressure (Pbs)", "~18 mmHg",
         "Opposes filtration", "Urinary obstruction, ureteral stones"],
        ["Glomerular oncotic pressure (pgc)", "~32 mmHg",
         "Opposes filtration", "Plasma protein levels, filtration fraction"],
        ["Net filtration pressure", "~10 mmHg",
         "Promotes filtration", "Sum of above"],
        ["GFR = Kf x NFP", "~125 mL/min",
         "—", "Kf reduced in glomerular disease"],
    ],
    col_widths=[5.5*cm, 2.5*cm, 3.5*cm, 5*cm]
))
story.append(formula("GFR = Kf × (Pgc – Pbs – πgc)  =  Kf × ~10 mmHg  =  ~125 mL/min"))
story.append(spacer(0.2))

story.append(sub_header("Renal Autoregulation (MAP 80–180 mmHg)"))
story.append(make_table(
    ["Mechanism", "Trigger", "Response"],
    [
        ["Myogenic", "Stretch of afferent arteriole wall from ↑BP",
         "Vasoconstriction of afferent arteriole → maintains GFR"],
        ["Tubuloglomerular feedback (TGF)", "Macula densa senses ↑NaCl delivery to DCT",
         "ATP/adenosine → afferent arteriolar constriction → ↓GFR"],
    ],
    col_widths=[4*cm, 6*cm, 6.5*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Factors Altering GFR"))
story.append(make_table(
    ["Increases GFR", "Decreases GFR"],
    [
        ["Afferent arteriole dilation (prostaglandins, ANP)",
         "Afferent arteriole constriction (sympathetic NS, Ang II high dose)"],
        ["↑ Blood pressure (within autoregulation)",
         "Efferent arteriole dilation (ACE inhibitors → ↓ efferent resistance)"],
        ["↓ Plasma oncotic pressure",
         "↑ Bowman's capsule pressure (obstruction)"],
        ["Efferent arteriole constriction (low-dose Ang II)",
         "↓ Kf (glomerulonephritis, diabetic nephropathy)"],
    ],
    col_widths=[8*cm, 8.5*cm]
))
story.append(PageBreak())

# ══════════════════════ SECTION 3: TUBULAR FUNCTION ══════════════════════
story.append(section_header("3.  Tubular Reabsorption &amp; Secretion", GREEN, ""))
story.append(spacer(0.2))
story.append(formula("Urinary Excretion = Glomerular Filtration − Reabsorption + Secretion"))
story.append(spacer(0.2))

story.append(sub_header("Proximal Convoluted Tubule (PCT)"))
story.append(info_box("PCT Reabsorbs ~65–70% of Filtered Load", [
    "Na+, Cl-, K+, HCO3-, water (all ~65-70%)",
    "Glucose: ~100% (via SGLT1/SGLT2 cotransporters with Na+)",
    "Amino acids: ~100% (via Na+-amino acid cotransporters)",
    "Urea: ~50% (passive diffusion)",
    "Reabsorption is ISOSMOTIC – fluid remains ~300 mOsm/L throughout PCT",
], bg=LIGHT_GREEN, border=GREEN))
story.append(spacer(0.2))
story.append(body(
    "<b>Mechanism:</b> Basolateral Na+/K+-ATPase pumps 3 Na+ out and 2 K+ in, maintaining "
    "low intracellular Na+. This gradient drives Na+ entry from lumen via: "
    "(1) Na+-glucose cotransporter (SGLT2) – site of SGLT2 inhibitor action; "
    "(2) Na+/H+ antiporter – couples Na+ entry with H+ secretion, reclaiming HCO3-; "
    "(3) Na+-amino acid cotransporters. Water follows Na+ via AQP1 channels (always open)."
))
story.append(spacer(0.2))
story.append(key_point("Glucose Tm: Transport maximum ~375 mg/min. Renal threshold ~180 mg/dL plasma glucose → glucosuria in diabetes."))
story.append(spacer(0.2))

story.append(sub_header("Loop of Henle"))
story.append(make_table(
    ["Segment", "Na+/Solute Transport", "Water Permeability", "Net Effect on Fluid"],
    [
        ["Thin descending limb", "No active transport; some Na+ entry",
         "High (AQP1 present)", "Water leaves; fluid becomes HYPERTONIC (up to 1200 mOsm)"],
        ["Thin ascending limb", "Passive NaCl diffusion out",
         "Impermeable", "Solute out, no water – slight dilution"],
        ["THICK ascending limb (TAL)", "Active Na+/K+/2Cl- cotransport (NKCC2) – FUROSEMIDE site",
         "IMPERMEABLE (no AQP)", "Fluid dilutes to ~100 mOsm (DILUTING SEGMENT)"],
    ],
    col_widths=[3.5*cm, 5*cm, 3.5*cm, 5*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Distal Convoluted Tubule (DCT)"))
story.append(body(
    "Reabsorbs Na+ and Cl- via the <b>NaCl cotransporter (NCC)</b> on the apical membrane – "
    "this is the site of action of <b>thiazide diuretics</b>. The DCT is water-impermeable "
    "in its early portion, continuing the dilution of tubular fluid. Late DCT responds to "
    "aldosterone. Fluid enters DCT at ~100 mOsm/L."
))
story.append(spacer(0.2))

story.append(sub_header("Collecting Duct – Final Fine-Tuning"))
story.append(make_table(
    ["Cell Type", "Apical Transporter", "Hormone", "Function"],
    [
        ["Principal cell", "ENaC (Na+ in), ROMK (K+ out), AQP2 (water)",
         "Aldosterone (Na+); ADH (water)", "Na+ reabsorption, K+ secretion, water reabsorption"],
        ["Alpha-intercalated cell", "H+-ATPase (H+ out), Cl-/HCO3- exchanger",
         "Acidosis stimulates", "H+ secretion; acid-base regulation"],
        ["Beta-intercalated cell", "Cl-/HCO3- exchanger (apical)",
         "Alkalosis stimulates", "HCO3- secretion; acid-base regulation"],
    ],
    col_widths=[3.5*cm, 5.5*cm, 3.5*cm, 4*cm]
))
story.append(PageBreak())

# ══════════════════════ SECTION 4: COUNTERCURRENT ══════════════════════
story.append(section_header("4.  Loop of Henle &amp; Countercurrent Mechanism", ORANGE, ""))
story.append(spacer(0.2))
story.append(body(
    "The countercurrent system creates and maintains a <b>hyperosmotic renal medullary "
    "interstitium</b> (up to 1200–1400 mOsm/L at the papillary tip vs. 300 mOsm/L in the "
    "cortex). This gradient is the essential prerequisite for producing concentrated urine."
))
story.append(spacer(0.3))
story.append(countercurrent_diagram())
story.append(Paragraph(
    "Fig 3. Countercurrent multiplier showing osmolarity values (mOsm/L) in each tubular segment",
    ST_CAPTION
))
story.append(spacer(0.2))

story.append(sub_header("How the Gradient is Built – Four Factors"))
story.append(make_table(
    ["Factor", "Mechanism", "Contribution"],
    [
        ["NKCC2 pump in thick ALH",
         "Active Na+/K+/2Cl- transport out of the thick ascending limb (impermeable to water)",
         "Primary driver – adds solute without water to medulla"],
        ["Urea recycling",
         "Inner medullary collecting duct (with ADH) reabsorbs urea via UT-A1/UT-A3 transporters",
         "Adds ~500 mOsm to inner medulla"],
        ["Thin descending limb",
         "Water exits down osmotic gradient into hypertonic interstitium via AQP1",
         "Concentrates tubular fluid delivered to bend"],
        ["Vasa recta (countercurrent exchanger)",
         "Descending vasa recta takes up solute; ascending loses it back – hairpin arrangement",
         "Prevents washout of medullary gradient"],
    ],
    col_widths=[3.5*cm, 7*cm, 6*cm]
))
story.append(spacer(0.3))
story.append(info_box("Clinical Pearl", [
    "Loop diuretics (furosemide, bumetanide) block NKCC2 in the thick ALH",
    "This destroys the medullary concentration gradient",
    "Collecting duct cannot concentrate urine even with maximal ADH → massive diuresis",
    "Also causes K+ wasting (reduces K+ recycling in TAL driving ROMK secretion)",
], bg=LIGHT_RED, border=RED))
story.append(PageBreak())

# ══════════════════════ SECTION 5: ADH / CONCENTRATION ══════════════════════
story.append(section_header("5.  Urine Concentration &amp; Dilution (ADH)", PURPLE, ""))
story.append(spacer(0.2))
story.append(sub_header("ADH (Vasopressin) Mechanism"))
story.append(body(
    "ADH is produced in the <b>supraoptic and paraventricular nuclei of the hypothalamus</b> "
    "and released from the posterior pituitary. It acts via V2 receptors on collecting duct "
    "principal cells → activates adenylyl cyclase → ↑cAMP → PKA → phosphorylation of "
    "AQP2 vesicles → insertion of <b>aquaporin-2 (AQP2)</b> into the apical membrane → "
    "collecting duct becomes water-permeable → water moves out into hypertonic medulla."
))
story.append(spacer(0.2))

story.append(make_table(
    ["Condition", "ADH Level", "Collecting Duct", "Urine Osmolarity", "Urine Volume"],
    [
        ["Dehydration / ↑plasma osmolarity", "HIGH", "Permeable (AQP2 inserted)",
         "Up to 1200–1400 mOsm/L", "Low (~500 mL/day)"],
        ["Overhydration / ↓plasma osmolarity", "LOW", "Impermeable (AQP2 absent)",
         "As low as 50–100 mOsm/L", "High (up to 20 L/day)"],
    ],
    col_widths=[4.5*cm, 2*cm, 4*cm, 4*cm, 3*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Stimuli for ADH Release"))
story.append(make_table(
    ["Stimulus", "Sensor", "Effect"],
    [
        ["↑ Plasma osmolarity (>280 mOsm)", "Osmoreceptors in anterior hypothalamus",
         "Primary regulator – even 1–2% change triggers ADH"],
        ["↓ Blood volume/pressure", "Baroreceptors (carotid, atria)", 
         "Requires >8–10% volume loss; more potent override"],
        ["Nausea, pain, stress", "CNS", "Stimulate ADH even at normal osmolarity"],
        ["Alcohol", "Hypothalamus", "INHIBITS ADH → diuresis (hence frequent urination with alcohol)"],
    ],
    col_widths=[5*cm, 5*cm, 6.5*cm]
))
story.append(spacer(0.2))

story.append(info_box("Diabetes Insipidus (DI) – Key Distinction", [
    "Central DI: ADH not produced/released (hypothalamic/pituitary damage) → massive hypotonic polyuria",
    "Nephrogenic DI: ADH present but collecting duct V2 receptors/AQP2 dysfunctional",
    "SIADH: Excess ADH → water retention → dilutional hyponatremia → concentrated urine",
    "Desmopressin (synthetic ADH) treats Central DI; corrects urine in CDI but not nephrogenic DI",
], bg=LIGHT_PURPLE, border=PURPLE))
story.append(PageBreak())

# ══════════════════════ SECTION 6: HORMONES ══════════════════════
story.append(section_header("6.  Hormonal Regulation of Renal Function", RED, ""))
story.append(spacer(0.2))
story.append(sub_header("Renin-Angiotensin-Aldosterone System (RAAS)"))
story.append(raas_diagram())
story.append(Paragraph("Fig 4. RAAS cascade from renin release to aldosterone effects", ST_CAPTION))
story.append(spacer(0.2))

story.append(make_table(
    ["Step", "Location", "What Happens"],
    [
        ["Renin release", "JG cells of afferent arteriole",
         "Triggered by: ↓ BP (stretch), ↓ NaCl at macula densa, ↑ sympathetic (beta-1)"],
        ["Angiotensinogen → Ang I", "Liver (angiotensinogen) + plasma",
         "Renin cleaves angiotensinogen to Ang I (inactive decapeptide)"],
        ["Ang I → Ang II", "Lung endothelium (ACE)",
         "ACE converts Ang I to Ang II (active octapeptide). ACE inhibitors block here"],
        ["Ang II effects", "Multiple organs",
         "(1) PCT: ↑ Na+/H+ antiporter → ↑ Na+ reabsorption; (2) Adrenal: → aldosterone; "
         "(3) Vasoconstriction; (4) ↑ ADH; (5) Thirst"],
        ["Aldosterone", "Collecting duct principal cells",
         "↑ ENaC and Na+/K+-ATPase → ↑ Na+ reabsorption, ↑ K+ secretion, water follows → ↑ BP"],
    ],
    col_widths=[3.5*cm, 4*cm, 9*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Other Key Hormones"))
story.append(make_table(
    ["Hormone", "Source", "Renal Action", "Net Effect"],
    [
        ["ANP (Atrial Natriuretic Peptide)", "Atria (↑stretch)",
         "Dilates afferent, constricts efferent → ↑GFR; ↓ renin; ↓ aldosterone; ↓ ADH",
         "Natriuresis + diuresis → ↓ blood volume"],
        ["PTH (Parathyroid Hormone)", "Parathyroid glands",
         "↑ Ca2+ reabsorption (DCT); ↓ phosphate reabsorption (PCT); "
         "activates 1α-hydroxylase → active Vit D",
         "↑ serum Ca2+, ↓ serum phosphate"],
        ["Dopamine", "Proximal tubule cells",
         "↓ Na+/K+-ATPase and NHE3 in PCT; ↓ aldosterone",
         "Natriuresis; used in low doses for renal protection"],
        ["Prostaglandins (PGE2)", "Renal medulla",
         "Dilate afferent arteriole → maintain GFR; antagonize ADH in collecting duct",
         "NSAIDs block → ↓ GFR, water retention"],
    ],
    col_widths=[3.5*cm, 3.5*cm, 6.5*cm, 3*cm]
))
story.append(PageBreak())

# ══════════════════════ SECTION 7: SPECIFIC SUBSTANCES ══════════════════════
story.append(section_header("7.  Renal Handling of Key Substances", NAVY, ""))
story.append(spacer(0.2))
story.append(make_table(
    ["Substance", "Filtered?", "PCT", "Loop of Henle", "DCT / CD", "Net Excretion"],
    [
        ["Sodium (Na+)", "Yes", "65-70% reabsorbed (Na+/K+-ATPase, NHE3, SGLT)",
         "25% TAL (NKCC2)", "~5% (aldosterone-regulated ENaC)", "<1%"],
        ["Glucose", "Yes", "~100% (SGLT1/2, Tm-limited)",
         "–", "–", "0 (unless >Tm)"],
        ["Potassium (K+)", "Yes", "65% reabsorbed",
         "25% reabsorbed (TAL via ROMK recycling)", "Secreted by principal cells (aldosterone)",
         "Variable; ~15% normally"],
        ["Urea", "Yes", "~50% reabsorbed (passive)",
         "Secreted (thin ALH)", "Reabsorbed (inner MCD, UT-A1 with ADH)", "~50%"],
        ["Creatinine", "Yes", "Minimal reabsorption",
         "–", "Small secretion", "~100% of filtered"],
        ["Bicarbonate (HCO3-)", "Yes", "80-90% reabsorbed (NHE3 + carbonic anhydrase)",
         "~5% TAL", "Final titration (intercalated cells)", "Very little (normal pH)"],
        ["Calcium (Ca2+)", "Yes (40% free)", "65% passive paracellular",
         "25% (TAL – paracellular, driven by lumen +ve potential)", 
         "Active transcellular (PTH-stimulated)", "<2%"],
        ["Phosphate", "Yes", "85% reabsorbed (NaPi-IIa cotransporter – inhibited by PTH)",
         "–", "–", "15% normally"],
        ["Uric acid", "Yes", "Reabsorbed AND secreted (net reabsorption 90%)",
         "–", "–", "~10%"],
        ["H+ (acid)", "–", "Secreted (NHE3 → reclaims HCO3-)",
         "–", "Secreted (H+-ATPase in intercalated cells)", "~80 mEq/day"],
    ],
    col_widths=[2.8*cm, 1.5*cm, 4.2*cm, 3*cm, 3.5*cm, 2.5*cm]
))
story.append(PageBreak())

# ══════════════════════ SECTION 8: ACID-BASE ══════════════════════
story.append(section_header("8.  Renal Acid–Base Balance", colors.HexColor("#6c3483"), ""))
story.append(spacer(0.2))
story.append(body(
    "The kidneys are the <b>long-term</b> regulators of body pH (lungs handle short-term CO2). "
    "Normal arterial pH = 7.35–7.45. The kidneys excrete ~80 mEq of fixed acid per day "
    "through three mechanisms:"
))
story.append(spacer(0.2))

story.append(make_table(
    ["Mechanism", "Where", "How It Works", "Significance"],
    [
        ["HCO3- Reabsorption", "PCT (~85%), TAL (~5%), CD",
         "H+ secreted via NHE3 (PCT) reacts with filtered HCO3-; "
         "carbonic anhydrase: H2CO3 → CO2+H2O; CO2 enters cell → reforms HCO3- → "
         "exits basolaterally. NET: reclaims filtered bicarbonate",
         "Not true acid excretion; reclaims bicarbonate buffer"],
        ["Titratable Acid (TA)", "Collecting duct",
         "H+ secreted by H+-ATPase combines with HPO4(2-) → H2PO4(-), "
         "which is excreted. Each H+ excreted regenerates 1 HCO3-",
         "~30-40 mEq/day; limited by phosphate availability"],
        ["Ammonium (NH4+)", "PCT generates NH3; CD secretes into lumen",
         "Glutamine → glutaminase → NH3 + H+ → NH4+ (trapped in lumen). "
         "Medullary recycling amplifies delivery to collecting duct",
         "~40-50 mEq/day; upregulated in chronic acidosis; most important buffer"],
    ],
    col_widths=[3.5*cm, 2.5*cm, 7*cm, 3.5*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Renal Compensation for Acid-Base Disorders"))
story.append(make_table(
    ["Disorder", "Primary Change", "Renal Compensation", "Time Course"],
    [
        ["Metabolic Acidosis", "↓ HCO3-", "↑ H+ secretion; ↑ NH4+ production; ↑ HCO3- generation",
         "Hours to days"],
        ["Metabolic Alkalosis", "↑ HCO3-", "↓ H+ secretion; ↑ HCO3- excretion (bicarbonaturia)",
         "Hours to days"],
        ["Respiratory Acidosis", "↑ PaCO2", "↑ H+ secretion; ↑ NH4+; ↑ HCO3- reabsorption",
         "2-5 days"],
        ["Respiratory Alkalosis", "↓ PaCO2", "↓ H+ secretion; ↑ HCO3- excretion",
         "2-5 days"],
    ],
    col_widths=[4*cm, 3*cm, 6.5*cm, 3*cm]
))
story.append(PageBreak())

# ══════════════════════ SECTION 9: CLEARANCE ══════════════════════
story.append(section_header("9.  Renal Clearance", GREEN, ""))
story.append(spacer(0.2))
story.append(formula("Clearance (C) = (Urine concentration × Urine flow rate) ÷ Plasma concentration = U×V / P"))
story.append(body(
    "<b>Clearance</b> represents the volume of plasma completely cleared of a substance per unit time. "
    "Comparing a substance's clearance to inulin clearance (= GFR) reveals whether it is "
    "reabsorbed, secreted, or neither."
))
story.append(spacer(0.2))

story.append(make_table(
    ["Substance", "Clearance (mL/min)", "Interpretation"],
    [
        ["Glucose",     "0",     "Fully reabsorbed below Tm"],
        ["Sodium",      "~0.9",  "Mostly reabsorbed; <1% excreted"],
        ["Urea",        "~70",   "Partly reabsorbed (clearance < GFR)"],
        ["Inulin",      "125",   "= GFR (gold standard – filtered only, not absorbed/secreted)"],
        ["Creatinine",  "~140",  "Slightly > GFR (some tubular secretion)"],
        ["PAH",         "~650",  "= Renal Plasma Flow (RPF) – nearly fully secreted"],
    ],
    col_widths=[4*cm, 4*cm, 8.5*cm]
))
story.append(spacer(0.2))

story.append(make_table(
    ["Derived Value", "Formula", "Normal Value"],
    [
        ["GFR", "Inulin clearance = Uin×V / Pin", "~125 mL/min"],
        ["Renal Plasma Flow (RPF)", "PAH clearance = UPAH×V / PPAH", "~650 mL/min"],
        ["Renal Blood Flow (RBF)", "RPF / (1 - Hematocrit)", "~1200 mL/min (~20% cardiac output)"],
        ["Filtration Fraction (FF)", "GFR / RPF", "~0.19 (19%)"],
    ],
    col_widths=[4.5*cm, 6.5*cm, 5.5*cm]
))
story.append(spacer(0.2))

story.append(info_box("Creatinine Clearance – Clinical Use", [
    "Endogenous creatinine clearance ~140 mL/min (slight overestimate of GFR due to tubular secretion)",
    "Cockcroft-Gault formula: CrCl = [(140 - age) x weight(kg)] / [72 x serum Cr(mg/dL)]  (x 0.85 for females)",
    "eGFR by CKD-EPI equation now preferred in clinical practice",
    "CKD staging: G1 (>90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), G5 (<15 mL/min/1.73m2)",
], bg=LIGHT_GREEN, border=GREEN))
story.append(PageBreak())

# ══════════════════════ SECTION 10: QUICK REFERENCE ══════════════════════
story.append(section_header("10.  Quick-Reference Tables &amp; Key Values", GOLD, ""))
story.append(spacer(0.2))

story.append(sub_header("Normal Renal Parameters"))
story.append(make_table(
    ["Parameter", "Normal Value"],
    [
        ["GFR",                           "125 mL/min (180 L/day)"],
        ["Renal Plasma Flow (RPF)",        "~650 mL/min"],
        ["Renal Blood Flow (RBF)",         "~1200 mL/min (20-25% cardiac output)"],
        ["Filtration Fraction",            "~19%"],
        ["Daily urine output",             "1-2 L/day"],
        ["Urine osmolarity range",         "50-1400 mOsm/L"],
        ["Plasma osmolarity",              "275-295 mOsm/L"],
        ["Maximum urine concentration",    "~1200-1400 mOsm/L (medullary tip)"],
        ["Normal serum creatinine",        "0.6-1.2 mg/dL (men); 0.5-1.1 (women)"],
        ["Normal GFR threshold for glucosuria", "Plasma glucose >180-200 mg/dL"],
    ],
    col_widths=[8*cm, 8.5*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Diuretic Sites of Action"))
story.append(make_table(
    ["Diuretic Class", "Site", "Transporter Blocked", "Key Effects"],
    [
        ["Carbonic anhydrase inhibitors\n(Acetazolamide)",
         "PCT",
         "Carbonic anhydrase → ↓ H+ secretion → ↓ HCO3- reclamation",
         "Bicarbonaturia; metabolic acidosis; weak diuresis"],
        ["Osmotic diuretics\n(Mannitol)",
         "PCT + Descending LOH",
         "Not a transporter; limits passive water reabsorption",
         "↑ urine volume; reduces cerebral edema"],
        ["Loop diuretics\n(Furosemide, Bumetanide)",
         "Thick ascending LOH",
         "NKCC2 (Na+/K+/2Cl-)",
         "Most potent; destroys medullary gradient; Ca2+ and Mg2+ wasting; K+ wasting"],
        ["Thiazides\n(Hydrochlorothiazide)",
         "Early DCT",
         "NCC (Na+/Cl-)",
         "Moderate diuresis; K+ wasting; Ca2+ RETENTION (useful in hypercalciuria/stones)"],
        ["K+-sparing diuretics\n(Spironolactone, Amiloride)",
         "Collecting duct",
         "Spiro: blocks aldosterone receptor; Amiloride: blocks ENaC",
         "Weak diuresis; hyperkalemia risk; no K+ wasting"],
        ["V2 receptor antagonists\n(Tolvaptan – 'Vaptans')",
         "Collecting duct",
         "V2 receptor → blocks AQP2 insertion",
         "Aquaresis (free water excretion); treats hyponatremia in SIADH/CHF"],
    ],
    col_widths=[3.5*cm, 2.5*cm, 4.5*cm, 6*cm]
))
story.append(spacer(0.2))

story.append(sub_header("Tubular Transport Mechanisms Summary"))
story.append(make_table(
    ["Transporter", "Location", "Moves", "Blocked By"],
    [
        ["Na+/K+-ATPase", "Basolateral (all segments)", "3Na+ out, 2K+ in", "Ouabain (experimentally)"],
        ["SGLT2 / SGLT1", "PCT apical", "Na+ + Glucose cotransport", "Gliflozins (SGLT2i – empagliflozin etc.)"],
        ["NHE3 (Na+/H+ antiporter)", "PCT apical", "Na+ in, H+ out", "Carbonic anhydrase inhibitors (indirectly)"],
        ["NKCC2", "Thick ALH apical", "Na+, K+, 2Cl- in", "Loop diuretics (furosemide)"],
        ["NCC", "DCT apical", "Na+, Cl- in", "Thiazides"],
        ["ENaC", "Collecting duct apical", "Na+ in", "Amiloride, spironolactone (indirectly)"],
        ["AQP1", "PCT + descending LOH", "Water (constitutive)", "Not regulated"],
        ["AQP2", "Collecting duct apical", "Water (regulated)", "Blocked by absence of ADH; tolvaptan"],
        ["H+-ATPase", "Intercalated cells apical", "H+ secretion", "—"],
    ],
    col_widths=[3.5*cm, 4*cm, 4.5*cm, 4.5*cm]
))
story.append(PageBreak())

# ══════════════════════ BACK PAGE: MNEMONICS & PEARLS ══════════════════════
story.append(section_header("Clinical Pearls &amp; Mnemonics", colors.HexColor("#1a5276"), ""))
story.append(spacer(0.2))

pearls = [
    ("GFR Memory Aid",
     ["180 L/day filtered, ~1.5 L excreted = 99%+ reabsorption",
      "125 mL/min = normal adult GFR (memorize this number)",
      "Creatinine clearance slightly overestimates GFR (tubular secretion adds ~10%)"]),
    ("Thick ALH = The 'Diluting Segment'",
     ["Pumps NaCl OUT (NKCC2), water stays in (impermeable)",
      "Fluid exits at ~100 mOsm – HYPOTONIC despite being in hypertonic medulla",
      "This is why loop diuretics are the most powerful – they destroy the gradient"]),
    ("Aldosterone vs. ADH",
     ["Aldosterone: controls Na+ (and hence VOLUME). 'Aldo controls Amount'",
      "ADH: controls water (and hence OSMOLARITY). 'ADH controls dilution/concentration'",
      "Both act on collecting duct but are independently regulated"]),
    ("ACE Inhibitors / ARBs & GFR",
     ["Block Ang II → dilate efferent arteriole → ↓ GFR",
      "Beneficial in proteinuria (↓ glomerular hypertension) but dangerous in renal artery stenosis",
      "Serum creatinine may rise 10-20% initially – acceptable and even expected"]),
    ("Potassium Handling Mnemonic",
     ["PCT + LOH = Reabsorb K+",
      "DCT/CD principal cells = Secrete K+ (under aldosterone)",
      "↑ aldosterone → ↑ K+ loss → hypokalemia",
      "K+-sparing diuretics (spiro, amiloride) prevent this loss"]),
    ("Starling Forces Memory: '60 opposes 50'",
     ["Promoting filtration: Pgc = 60 mmHg",
      "Opposing: Pbs (18) + pgc (32) = 50 mmHg",
      "Net = 60 - 50 = 10 mmHg promoting filtration"]),
]

for (title, pts) in pearls:
    bg = LIGHT_BLUE if pearls.index((title,pts)) % 2 == 0 else LIGHT_GREEN
    story.append(info_box(title, pts, bg=bg, border=TEAL))
    story.append(spacer(0.2))

# Footer note
story.append(hr(GRAY))
story.append(Paragraph(
    "<i>Study Guide compiled from Guyton &amp; Hall Textbook of Medical Physiology 14E, "
    "Ganong's Review of Medical Physiology 26E, Costanzo Physiology 7E, and "
    "Brenner &amp; Rector's The Kidney. For educational use only.</i>",
    ST_CAPTION
))

# ─────────────────────────────────────────────────────────
# Build
# ─────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUTPUT}")
print(f"Size: {os.path.getsize(OUTPUT):,} bytes")

cd /home/daytona/workspace/renal-physiology-guide && python3 create_pdf.py 2>&1

~/renal-physiology-guide/create_pdf.py

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/renal-physiology-guide/create_pdf.py'

cd /home/daytona/workspace/renal-physiology-guide && python3 create_pdf.py 2>&1

python3 -c " from pypdf import PdfReader r = PdfReader('/home/daytona/workspace/…