Glucocorticoids: Structure, Synthesis, and Functions

import requests
import os
from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.lib import colors
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, Image, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import PageBreak
from io import BytesIO

OUTPUT = "/home/daytona/workspace/glucocorticoid-seminar/Glucocorticoids_Seminar.pdf"

# Download adrenal image
IMG_URL = "https://cdn.orris.care/cdss_images/8d85859e6b8de42c81b30c446cd3dc7fc709223700316f9579346f2e4ffd7a6c.png"
img_path = "/home/daytona/workspace/glucocorticoid-seminar/adrenal.png"
if not os.path.exists(img_path):
    r = requests.get(IMG_URL, timeout=20)
    with open(img_path, "wb") as f:
        f.write(r.content)
    print("Image downloaded")

# ----- Styles -----
styles = getSampleStyleSheet()

TEAL  = colors.HexColor("#1A6B72")
LTEAL = colors.HexColor("#E8F5F6")
GOLD  = colors.HexColor("#C8860A")
DGRAY = colors.HexColor("#2D2D2D")
MGRAY = colors.HexColor("#555555")
LGRAY = colors.HexColor("#F4F6F7")
WHITE = colors.white

title_style = ParagraphStyle("Title", parent=styles["Normal"],
    fontSize=22, textColor=WHITE, fontName="Helvetica-Bold",
    alignment=TA_CENTER, spaceAfter=4)

subtitle_style = ParagraphStyle("Subtitle", parent=styles["Normal"],
    fontSize=11, textColor=colors.HexColor("#D0EEF0"),
    fontName="Helvetica", alignment=TA_CENTER, spaceAfter=2)

h1_style = ParagraphStyle("H1", parent=styles["Normal"],
    fontSize=14, textColor=WHITE, fontName="Helvetica-Bold",
    alignment=TA_LEFT, spaceBefore=4, spaceAfter=4,
    leftIndent=6)

h2_style = ParagraphStyle("H2", parent=styles["Normal"],
    fontSize=11, textColor=TEAL, fontName="Helvetica-Bold",
    spaceBefore=10, spaceAfter=3)

h3_style = ParagraphStyle("H3", parent=styles["Normal"],
    fontSize=10, textColor=GOLD, fontName="Helvetica-Bold",
    spaceBefore=7, spaceAfter=2)

body_style = ParagraphStyle("Body", parent=styles["Normal"],
    fontSize=9.5, textColor=DGRAY, fontName="Helvetica",
    leading=14, spaceAfter=4, alignment=TA_JUSTIFY)

bullet_style = ParagraphStyle("Bullet", parent=styles["Normal"],
    fontSize=9.5, textColor=MGRAY, fontName="Helvetica",
    leading=14, leftIndent=14, bulletIndent=4, spaceAfter=2)

note_style = ParagraphStyle("Note", parent=styles["Normal"],
    fontSize=8.5, textColor=MGRAY, fontName="Helvetica-Oblique",
    leading=12, spaceAfter=4)

footer_style = ParagraphStyle("Footer", parent=styles["Normal"],
    fontSize=7.5, textColor=MGRAY, fontName="Helvetica",
    alignment=TA_CENTER)

def section_header(text, style=h1_style, bg=TEAL):
    data = [[Paragraph(text, style)]]
    t = Table(data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("ROUNDEDCORNERS", [4]),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
    ]))
    return t

def info_box(text, bg=LTEAL, border=TEAL):
    data = [[Paragraph(text, ParagraphStyle("IB", parent=body_style, textColor=colors.HexColor("#0D4A50")))]]
    t = Table(data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0), (-1,-1), bg),
        ("LEFTPADDING",  (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("TOPPADDING",   (0,0), (-1,-1), 6),
        ("BOTTOMPADDING",(0,0), (-1,-1), 6),
        ("LINEAFTER",    (0,0), (0,-1), 3, border),
    ]))
    return t

def bullet(text):
    return Paragraph(f"•   {text}", bullet_style)

def sp(n=6):
    return Spacer(1, n)

def hr():
    return HRFlowable(width="100%", thickness=0.5, color=colors.HexColor("#CCCCCC"), spaceAfter=4)

# ===== BUILD STORY =====
story = []

# ---- TITLE BLOCK ----
title_data = [[
    Paragraph("GLUCOCORTICOIDS", title_style),
    Paragraph("Structure, Synthesis & Functions", subtitle_style),
    Paragraph("MBBS First Year Physiology Seminar", subtitle_style),
]]
title_table = Table([[Paragraph("GLUCOCORTICOIDS", title_style)],
                     [Paragraph("Structure, Synthesis & Functions", subtitle_style)],
                     [Paragraph("MBBS First Year Physiology Seminar", subtitle_style)]],
                    colWidths=[17*cm])
title_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), TEAL),
    ("TOPPADDING",    (0,0), (-1,-1), 14),
    ("BOTTOMPADDING", (0,0), (-1,-1), 14),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
    ("ROUNDEDCORNERS",[5]),
]))
story.append(title_table)
story.append(sp(12))

# ---- 1. INTRODUCTION ----
story.append(section_header("1. Introduction"))
story.append(sp(6))
story.append(Paragraph(
    "Glucocorticoids are <b>steroid hormones</b> produced by the <b>zona fasciculata</b> of the adrenal cortex. "
    "The primary glucocorticoid in humans is <b>cortisol</b> (hydrocortisone). Corticosterone is a minor "
    "glucocorticoid; in rodents it is the principal one. The adrenal gland sits atop each kidney; its cortex "
    "has three zones:",
    body_style))
story.append(sp(4))

zone_data = [
    [Paragraph("<b>Zone</b>", body_style), Paragraph("<b>Location</b>", body_style), Paragraph("<b>Hormone</b>", body_style)],
    ["Zona Glomerulosa", "Outer", "Mineralocorticoids (Aldosterone)"],
    ["Zona Fasciculata", "Middle (largest)", "Glucocorticoids (Cortisol) ✓"],
    ["Zona Reticularis", "Inner", "Androgens (DHEA, Androstenedione)"],
]
zone_table = Table(zone_data, colWidths=[5.5*cm, 4.5*cm, 7*cm])
zone_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#BBBBBB")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("BACKGROUND",    (0,2), (-1,2), colors.HexColor("#D6EFF1")),
    ("FONTNAME",      (0,2), (-1,2), "Helvetica-Bold"),
]))
story.append(zone_table)
story.append(sp(8))

# Adrenal image
try:
    img = Image(img_path, width=6.5*cm, height=8.5*cm)
    img_caption = Paragraph(
        "<i>Fig: Adrenal gland anatomy showing three cortical zones and their hormones</i><br/>"
        "<i>(Medical Physiology - Boron &amp; Boulpaep, p. 1496)</i>", note_style)
    img_data = [[img, img_caption]]
    img_table = Table(img_data, colWidths=[7*cm, 10*cm])
    img_table.setStyle(TableStyle([
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
    ]))
    story.append(img_table)
except Exception as e:
    print(f"Image error: {e}")
story.append(sp(8))

# ---- 2. CHEMICAL NATURE & SYNTHESIS ----
story.append(section_header("2. Chemical Nature and Biosynthesis"))
story.append(sp(6))
story.append(Paragraph(
    "Glucocorticoids are <b>lipid-soluble steroid hormones</b> derived from <b>cholesterol</b>. "
    "Normal daily cortisol secretion is <b>15-25 mg/day</b>, surging up to 10x during severe stress.",
    body_style))
story.append(sp(4))

story.append(Paragraph("Key Biosynthetic Steps:", h3_style))
synth_steps = [
    ("Cholesterol", "→ Pregnenolone", "P450scc / CYP11A1", "Mitochondria"),
    ("Pregnenolone", "→ Progesterone", "3β-HSD", "SER"),
    ("Progesterone", "→ 17α-OH Progesterone", "CYP17 / 17α-hydroxylase", "SER"),
    ("17α-OH Progesterone", "→ 11-Deoxycortisol", "CYP21A2 / 21β-hydroxylase", "SER"),
    ("11-Deoxycortisol", "→ <b>CORTISOL</b>", "CYP11B1 / 11β-hydroxylase", "Mitochondria"),
]
synth_data = [[Paragraph("<b>From</b>", body_style), Paragraph("<b>To</b>", body_style),
               Paragraph("<b>Enzyme</b>", body_style), Paragraph("<b>Location</b>", body_style)]]
for row in synth_steps:
    synth_data.append([Paragraph(row[0], body_style), Paragraph(row[1], body_style),
                       Paragraph(row[2], body_style), Paragraph(row[3], body_style)])
synth_table = Table(synth_data, colWidths=[3.8*cm, 3.8*cm, 5.4*cm, 4*cm])
synth_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), GOLD),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 6),
    ("BACKGROUND",    (0,5), (-1,5), colors.HexColor("#FFF0CC")),
    ("FONTNAME",      (0,5), (-1,5), "Helvetica-Bold"),
]))
story.append(synth_table)
story.append(sp(4))
story.append(info_box(
    "<b>Key point:</b> Zona fasciculata has both 11β-hydroxylase AND 17α-hydroxylase → makes cortisol. "
    "Zona glomerulosa lacks 17α-hydroxylase → cannot make cortisol, only aldosterone."
))
story.append(sp(10))

# ---- 3. HPA AXIS ----
story.append(section_header("3. Regulation: The HPA Axis"))
story.append(sp(6))
story.append(Paragraph(
    "Cortisol secretion is controlled by the <b>Hypothalamo-Pituitary-Adrenal (HPA) Axis</b>:",
    body_style))
story.append(sp(4))

hpa_data = [
    [Paragraph("Hypothalamus (PVN)", ParagraphStyle("hpa", parent=body_style, alignment=TA_CENTER, textColor=WHITE, fontName="Helvetica-Bold")),
     Paragraph("Releases <b>CRH</b> (41-amino acid peptide). Triggers: circadian rhythm, stress, hypoglycemia, trauma.", body_style)],
    [Paragraph("↓", ParagraphStyle("arr", parent=body_style, alignment=TA_CENTER, fontSize=14, textColor=TEAL)), ""],
    [Paragraph("Anterior Pituitary", ParagraphStyle("hpa2", parent=body_style, alignment=TA_CENTER, textColor=WHITE, fontName="Helvetica-Bold")),
     Paragraph("Corticotrophs secrete <b>ACTH</b> (39-amino acid, from POMC precursor). Acts via cAMP → PKA → steroidogenesis.", body_style)],
    [Paragraph("↓", ParagraphStyle("arr", parent=body_style, alignment=TA_CENTER, fontSize=14, textColor=TEAL)), ""],
    [Paragraph("Zona Fasciculata", ParagraphStyle("hpa3", parent=body_style, alignment=TA_CENTER, textColor=WHITE, fontName="Helvetica-Bold")),
     Paragraph("Secretes <b>Cortisol</b>. Exerts <b>negative feedback</b> on both hypothalamus and anterior pituitary.", body_style)],
]
hpa_table = Table(hpa_data, colWidths=[4.5*cm, 12.5*cm])
hpa_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (0,0), TEAL),
    ("BACKGROUND",    (0,2), (0,2), colors.HexColor("#2980B9")),
    ("BACKGROUND",    (0,4), (0,4), colors.HexColor("#27AE60")),
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING",    (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING",   (0,0), (0,-1), 4),
    ("LEFTPADDING",   (1,0), (1,-1), 8),
    ("SPAN",          (1,1), (1,1)),
    ("SPAN",          (1,3), (1,3)),
]))
story.append(hpa_table)
story.append(sp(6))
story.append(bullet("<b>Circadian rhythm:</b> Cortisol peaks at 6-8 AM (just before waking), lowest at midnight"))
story.append(bullet("<b>Stress override:</b> Any physical/psychological stress overrides negative feedback → rapid cortisol surge"))
story.append(bullet("<b>AVP (vasopressin)</b> from PVN also acts as a potent ACTH secretagogue, especially during dehydration/trauma"))
story.append(sp(10))

# ---- 4. MECHANISM OF ACTION ----
story.append(section_header("4. Mechanism of Action"))
story.append(sp(6))
moa_steps = [
    "Cortisol (lipid-soluble) <b>diffuses freely</b> across cell membrane",
    "Binds intracellular <b>Glucocorticoid Receptors (GR)</b> - present in nearly every cell",
    "Hormone-receptor complex translocates to <b>nucleus</b>",
    "Binds <b>Glucocorticoid Response Elements (GREs)</b> on DNA",
    "Either <b>activates or represses</b> transcription of target genes (genomic action)",
    "<b>Non-genomic actions</b> also occur (0-3 hours) - rapid stress responses, not inhibited by transcription blockers",
]
for i, step in enumerate(moa_steps, 1):
    data = [[Paragraph(str(i), ParagraphStyle("num", parent=body_style, alignment=TA_CENTER, textColor=WHITE, fontName="Helvetica-Bold")),
             Paragraph(step, body_style)]]
    t = Table(data, colWidths=[1*cm, 16*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (0,0), TEAL),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (1,0), (1,0), 8),
        ("ROUNDEDCORNERS", [3]),
    ]))
    story.append(t)
    story.append(sp(3))
story.append(sp(8))

# ---- 5. FUNCTIONS ----
story.append(section_header("5. Functions of Glucocorticoids"))
story.append(sp(6))

# 5A Metabolic
story.append(Paragraph("A. Metabolic Effects", h2_style))
story.append(Paragraph("<b>Carbohydrate Metabolism (Diabetogenic):</b>", h3_style))
for b in [
    "Increases <b>hepatic gluconeogenesis</b> and glycogenesis (liver makes more glucose)",
    "Increases <b>glucose-6-phosphatase</b> activity",
    "Decreases peripheral glucose uptake (<b>anti-insulin effect</b>) in muscles and adipose",
    "Net result: <b>raises blood glucose</b>",
    "In adrenal insufficiency: fasting → fatal <b>hypoglycemia</b>",
]:
    story.append(bullet(b))
story.append(sp(4))

story.append(Paragraph("<b>Protein Metabolism:</b>", h3_style))
for b in [
    "Promotes <b>protein catabolism</b> in muscles, bone, skin, lymphoid tissue",
    "Mobilizes amino acids → liver → gluconeogenesis substrate",
    "Net: <b>negative nitrogen balance</b>, muscle wasting in excess (Cushing's syndrome)",
]:
    story.append(bullet(b))
story.append(sp(4))

story.append(Paragraph("<b>Fat Metabolism:</b>", h3_style))
for b in [
    "Promotes <b>lipolysis</b> in peripheral fat depots → mobilizes free fatty acids (FFAs)",
    "Permissive effect on catecholamine-induced lipolysis",
    "In excess: <b>fat redistribution</b> - central obesity, buffalo hump, moon facies",
]:
    story.append(bullet(b))
story.append(sp(8))

# 5B Anti-inflammatory
story.append(Paragraph("B. Anti-Inflammatory and Immunosuppressive Effects", h2_style))
story.append(info_box(
    "<b>Glucocorticoids are the most potent natural anti-inflammatory agents</b> and the most widely "
    "used anti-inflammatory drugs in clinical medicine."
))
story.append(sp(4))
story.append(Paragraph("Mechanisms of anti-inflammatory action:", body_style))
anti_data = [
    [Paragraph("<b>Mechanism</b>", body_style), Paragraph("<b>Effect</b>", body_style)],
    ["Stabilize lysosomal membranes", "Prevent release of destructive lysosomal enzymes"],
    ["Inhibit phospholipase A₂ (via lipocortin)", "↓ Arachidonic acid → ↓ Prostaglandins & Leukotrienes"],
    ["Inhibit NF-κB transcription factor", "↓ IL-1, IL-2, IL-6, TNF-α (pro-inflammatory cytokines)"],
    ["↓ IL-2 → lymphocyte apoptosis", "↓ Lymphocyte proliferation"],
    ["Reduce capillary permeability", "↓ Edema and exudate at inflammation site"],
    ["↓ Migration of neutrophils/macrophages", "Reduced cellular infiltration at inflammation site"],
]
anti_table = Table(anti_data, colWidths=[8.5*cm, 8.5*cm])
anti_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), colors.HexColor("#2980B9")),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
]))
story.append(anti_table)
story.append(sp(6))

story.append(Paragraph("Blood Cell Changes with Elevated Cortisol:", h3_style))
blood_data = [
    [Paragraph("<b>Cell Type</b>", body_style), Paragraph("<b>Effect</b>", body_style),
     Paragraph("<b>Normal (/µL)</b>", body_style), Paragraph("<b>Cortisol-treated (/µL)</b>", body_style)],
    ["Neutrophils (PMNs)", "↑ Increase (demargination)", "5760", "8330"],
    ["Lymphocytes", "↓ Decrease (apoptosis)", "2370", "1080"],
    ["Eosinophils", "↓↓ Marked decrease (sequestration)", "270", "20"],
    ["Basophils", "↓ Decrease", "60", "30"],
    ["Red Blood Cells", "↑ Slight increase", "5 million", "5.2 million"],
    ["Platelets", "↑ Increase", "-", "↑"],
]
blood_table = Table(blood_data, colWidths=[4.5*cm, 5.5*cm, 3.5*cm, 3.5*cm])
blood_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("BACKGROUND",    (0,3), (-1,3), colors.HexColor("#FFE8E8")),
]))
story.append(blood_table)
story.append(sp(4))
story.append(info_box(
    "<b>Classic exam point:</b> Eosinopenia + Lymphopenia is a hallmark of elevated cortisol "
    "(Cushing's syndrome or patients on corticosteroid therapy)."
))
story.append(sp(10))

# 5C Cardiovascular
story.append(Paragraph("C. Cardiovascular Effects (Permissive Action)", h2_style))
for b in [
    "Glucocorticoids must be present for <b>catecholamines</b> to exert full vasoconstrictor effects",
    "In adrenal insufficiency: vascular smooth muscle becomes <b>unresponsive to norepinephrine/epinephrine</b>",
    "Capillaries dilate → become permeable → <b>vascular collapse and shock</b>",
    "Glucocorticoids <b>restore vascular reactivity</b> - this is the 'permissive action'",
    "This explains why <b>Addison's disease</b> patients are prone to circulatory shock during stress",
]:
    story.append(bullet(b))
story.append(sp(8))

# 5D Water & Electrolytes
story.append(Paragraph("D. Effects on Water and Electrolyte Balance", h2_style))
for b in [
    "Required for normal <b>water excretion</b> - adrenal insufficiency → inability to excrete water load → water intoxication",
    "Mechanism: glucocorticoids raise <b>GFR</b> and suppress <b>ADH (vasopressin)</b> levels",
    "At high doses (pharmacologic): <b>mild mineralocorticoid activity</b> → Na⁺ retention, K⁺ excretion",
    "At physiological levels: minimal salt retention due to renal inactivation by 11β-HSD",
]:
    story.append(bullet(b))
story.append(sp(8))

# 5E CNS
story.append(Paragraph("E. Effects on the Central Nervous System", h2_style))
for b in [
    "Regulate <b>mood, behavior, and cognition</b>",
    "In deficiency (Addison's): irritability, anxiety, inability to concentrate, slow EEG",
    "In excess (Cushing's/steroid therapy): <b>euphoria, mood swings, steroid psychosis</b>",
    "Regulate <b>sleep-wake cycles</b> and contribute to feelings of well-being",
]:
    story.append(bullet(b))
story.append(sp(8))

# 5F Bone & Calcium
story.append(Paragraph("F. Effects on Bone and Calcium Metabolism", h2_style))
for b in [
    "Decrease <b>intestinal Ca²⁺ absorption</b> (antagonize Vitamin D)",
    "Increase <b>renal Ca²⁺ excretion</b>",
    "Promote <b>bone resorption</b> and reduce bone formation (inhibit osteoblasts)",
    "Long-term excess → <b>Osteoporosis</b> (major complication of chronic steroid therapy)",
]:
    story.append(bullet(b))
story.append(sp(8))

# 5G Other
story.append(Paragraph("G. Effects on Other Tissues", h2_style))
other_data = [
    [Paragraph("<b>Tissue</b>", body_style), Paragraph("<b>Effect</b>", body_style)],
    ["Skeletal Muscle", "Wasting and weakness at large doses (steroid myopathy)"],
    ["Skin", "Thinning, easy bruising, impaired wound healing (inhibit fibroblasts)"],
    ["Eye", "Increased intraocular pressure → risk of glaucoma"],
    ["GI Tract", "↑ Gastric acid and pepsin secretion → risk of peptic ulcers"],
    ["Lungs (Fetal)", "Promote surfactant synthesis → betamethasone used in premature labour"],
    ["Stress Response", "Essential for survival during severe stress (maintains vascular tone)"],
]
other_table = Table(other_data, colWidths=[5*cm, 12*cm])
other_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), GOLD),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
]))
story.append(other_table)
story.append(sp(10))

# ---- 6. CLINICAL CORRELATES ----
story.append(section_header("6. Clinical Correlates"))
story.append(sp(6))
story.append(Paragraph(
    "Understanding glucocorticoid excess and deficiency is essential for MBBS exams:",
    body_style))
story.append(sp(4))
clin_data = [
    [Paragraph("<b>Condition</b>", body_style), Paragraph("<b>Cause</b>", body_style), Paragraph("<b>Key Features</b>", body_style)],
    [Paragraph("<b>Cushing's Syndrome</b>", ParagraphStyle("cs", parent=body_style, textColor=colors.HexColor("#C0392B"))),
     "Glucocorticoid EXCESS\n(pituitary adenoma, adrenal tumor, exogenous steroids)",
     "Central obesity, moon face, buffalo hump, purple striae, hypertension, hyperglycemia, osteoporosis, eosinopenia"],
    [Paragraph("<b>Addison's Disease</b>", ParagraphStyle("ad", parent=body_style, textColor=colors.HexColor("#27AE60"))),
     "Primary adrenal insufficiency\n(autoimmune, TB, infarction)",
     "Hypoglycemia, hypotension, weakness, fatigue, hyperpigmentation (↑ACTH/MSH), inability to respond to stress → Addisonian crisis"],
    [Paragraph("<b>Congenital Adrenal Hyperplasia</b>", ParagraphStyle("cah", parent=body_style, textColor=colors.HexColor("#8E44AD"))),
     "Enzyme deficiency\n(usually 21-hydroxylase deficiency)",
     "Impaired cortisol synthesis → no negative feedback → excess ACTH → adrenal hyperplasia + androgen excess → virilization"],
]
clin_table = Table(clin_data, colWidths=[4*cm, 5.5*cm, 7.5*cm])
clin_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [colors.HexColor("#FFF5F5"), colors.HexColor("#F5FFF5"), colors.HexColor("#F9F5FF")]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 7),
    ("BOTTOMPADDING", (0,0), (-1,-1), 7),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("VALIGN",        (0,0), (-1,-1), "TOP"),
]))
story.append(clin_table)
story.append(sp(10))

# ---- 7. SUMMARY TABLE ----
story.append(section_header("7. Summary: Functions at a Glance"))
story.append(sp(6))
summary_data = [
    [Paragraph("<b>System</b>", body_style), Paragraph("<b>Effect of Glucocorticoids</b>", body_style)],
    ["Carbohydrate", "↑ Blood glucose, ↑ gluconeogenesis, anti-insulin action"],
    ["Protein", "↑ Catabolism, ↑ amino acid mobilization (negative N balance)"],
    ["Fat", "↑ Lipolysis, ↑ FFA; excess → central fat redistribution"],
    ["Immune / Inflammatory", "Anti-inflammatory, immunosuppressive (↓ cytokines, ↓ WBCs)"],
    ["Cardiovascular", "Permissive for catecholamine action, ↑ BP, maintains vascular tone"],
    ["Water Balance", "↑ GFR, ↓ ADH → enables water excretion"],
    ["CNS", "Mood, behavior, circadian regulation, well-being"],
    ["Bone / Calcium", "↑ Bone resorption, ↓ Ca²⁺ absorption → osteoporosis (excess)"],
    ["Blood Cells", "↑ Neutrophils, RBCs; ↓ Lymphocytes, Eosinophils, Basophils"],
    ["Stress Response", "ESSENTIAL for survival during severe stress"],
]
sum_table = Table(summary_data, colWidths=[5*cm, 12*cm])
sum_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("FONTNAME",      (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE",      (0,0), (-1,-1), 9),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [LGRAY, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("BACKGROUND",    (0,10), (-1,10), colors.HexColor("#D6EFF1")),
    ("FONTNAME",      (0,10), (-1,10), "Helvetica-Bold"),
]))
story.append(sum_table)
story.append(sp(10))

# ---- SOURCES ----
story.append(hr())
story.append(Paragraph("<b>References / Sources:</b>", h3_style))
story.append(bullet("Ganong's Review of Medical Physiology, 26th Ed. - Chapters 19 & 24 (Glucocorticoid Binding, HPA Axis, Permissive Action, Blood Cell Effects)"))
story.append(bullet("Medical Physiology (Boron & Boulpaep) - Chapter 50: The Adrenal Cortex: Cortisol"))
story.append(bullet("Janeway's Immunobiology, 10th Ed. - Chapter 16 (Anti-inflammatory mechanisms of corticosteroids)"))
story.append(sp(4))

# ---- PAGE NUMBERS via a canvas ----
def add_page_number(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(colors.HexColor("#888888"))
    page_num = canvas.getPageNumber()
    text = f"Glucocorticoids - MBBS First Year Physiology   |   Page {page_num}"
    canvas.drawCentredString(A4[0] / 2, 1.2*cm, text)
    canvas.restoreState()

# ---- BUILD PDF ----
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2*cm, bottomMargin=2.5*cm,
    title="Glucocorticoids - MBBS Physiology Seminar",
    author="Orris Medical AI",
)
doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number)
print(f"PDF created: {OUTPUT}")