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,
    HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import PageBreak

OUTPUT = "/tmp/workspace/knruhs-biochem/KNRUHS_Biochem_CheatSheet.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=1.5*cm,
    leftMargin=1.5*cm,
    topMargin=1.8*cm,
    bottomMargin=1.8*cm,
)

# ── colour palette ──────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1a3a5c")
MED_BLUE    = colors.HexColor("#2e6da4")
LIGHT_BLUE  = colors.HexColor("#d6e8f7")
ACCENT      = colors.HexColor("#e8a020")
ACCENT_LIGHT= colors.HexColor("#fff4dc")
GREEN       = colors.HexColor("#1e7a44")
GREEN_LIGHT = colors.HexColor("#d4f0e0")
RED_LIGHT   = colors.HexColor("#fde8e8")
RED         = colors.HexColor("#c0392b")
GREY_BG     = colors.HexColor("#f4f6f9")
WHITE       = colors.white

styles = getSampleStyleSheet()

def S(name, **kw):
    """Helper: clone a base style with overrides."""
    base = styles.get(name, styles["Normal"])
    return ParagraphStyle(
        name + "_custom_" + str(id(kw)),
        parent=base,
        **kw
    )

# ── custom styles ────────────────────────────────────────────────────
cover_title   = S("Title",  fontSize=26, textColor=WHITE,
                  alignment=TA_CENTER, leading=32, spaceAfter=6)
cover_sub     = S("Normal", fontSize=13, textColor=ACCENT,
                  alignment=TA_CENTER, leading=18, spaceAfter=4)
cover_note    = S("Normal", fontSize=9,  textColor=colors.HexColor("#ccddee"),
                  alignment=TA_CENTER, leading=13)

sec_heading   = S("Heading1", fontSize=11, textColor=WHITE,
                  alignment=TA_LEFT, leading=14, spaceBefore=2, spaceAfter=2)
topic_num     = S("Normal",  fontSize=10, textColor=DARK_BLUE,
                  alignment=TA_LEFT, leading=13, fontName="Helvetica-Bold")
body_text     = S("Normal",  fontSize=8.5, textColor=colors.HexColor("#222222"),
                  alignment=TA_LEFT, leading=12)
bullet_style  = S("Normal",  fontSize=8.2, textColor=colors.HexColor("#333333"),
                  alignment=TA_LEFT, leading=11.5, leftIndent=10)
key_point     = S("Normal",  fontSize=8,  textColor=GREEN,
                  fontName="Helvetica-Bold", alignment=TA_LEFT, leading=11)
clinical_style= S("Normal",  fontSize=8,  textColor=RED,
                  fontName="Helvetica-BoldOblique", alignment=TA_LEFT, leading=11)
footer_style  = S("Normal",  fontSize=7.5, textColor=colors.HexColor("#777777"),
                  alignment=TA_CENTER)

# ════════════════════════════════════════════════════════════════════
# DATA  –  top 20 topics
# Each entry: (number, title, bullets, key_points, clinical_note)
# ════════════════════════════════════════════════════════════════════
TOPICS = [
    (
        1, "Glycolysis",
        [
            "10 steps: Glucose → 2 Pyruvate",
            "Net yield: 2 ATP + 2 NADH (anaerobic); up to 8 ATP (aerobic)",
            "Key enzymes: Hexokinase, PFK-1 (rate-limiting), Pyruvate kinase",
            "Regulated by: AMP↑, ATP↓, citrate↓ on PFK-1",
            "Substrate-level phosphorylation at steps 7 & 10",
        ],
        "PFK-1 = rate-limiting enzyme of glycolysis",
        "Clinical: PFK-1 deficiency → Tarui disease (type VII GSD)"
    ),
    (
        2, "TCA Cycle (Krebs Cycle)",
        [
            "8 reactions; occurs in mitochondrial matrix",
            "Inputs: 2 Acetyl-CoA per glucose → 2×(3 NADH + 1 FADH2 + 1 GTP)",
            "Rate-limiting enzyme: Isocitrate dehydrogenase",
            "Key intermediates: Citrate, Isocitrate, α-KG, Succinyl-CoA, Succinate, Fumarate, Malate, OAA",
            "Amphibolic pathway (anabolic + catabolic)",
        ],
        "Isocitrate DH = rate-limiting; inhibited by ATP, NADH",
        "Clinical: Thiamine (B1) deficiency → inhibits α-KG DH → Wernicke's"
    ),
    (
        3, "HMP Shunt (Pentose Phosphate Pathway)",
        [
            "Occurs in cytoplasm; no ATP generated",
            "Produces: NADPH (antioxidant) + Ribose-5-phosphate (nucleotide synthesis)",
            "Rate-limiting enzyme: G6PD",
            "Oxidative phase: G6P → Ribulose-5-P (irreversible)",
            "Non-oxidative phase: interconverts sugar phosphates",
        ],
        "G6PD deficiency → NADPH↓ → RBC hemolysis (Heinz bodies)",
        "Clinical: G6PD deficiency = most common enzymopathy; triggered by primaquine, fava beans"
    ),
    (
        4, "Glycogen Metabolism",
        [
            "Synthesis (Glycogenesis): Glucose → UDP-Glucose → Glycogen; key enzyme = Glycogen synthase",
            "Breakdown (Glycogenolysis): Glycogen → G1P → G6P; key enzyme = Glycogen phosphorylase",
            "Branching enzyme adds α-1,6 branches; Debranching enzyme removes them",
            "Liver glycogen: blood glucose homeostasis; Muscle glycogen: local energy",
            "Regulated by: insulin (synthesis↑), glucagon/epinephrine (breakdown↑)",
        ],
        "Von Gierke (Type I) = G6Pase deficiency → severe hypoglycemia",
        "Clinical: McArdle (Type V) = muscle phosphorylase deficiency → exercise intolerance"
    ),
    (
        5, "Gluconeogenesis",
        [
            "Synthesis of glucose from non-carb precursors (lactate, alanine, glycerol, OAA)",
            "Occurs in: liver (90%), kidney cortex (10%)",
            "Key enzymes: PEPCK, Fructose-1,6-bisphosphatase, G6Pase, Pyruvate carboxylase",
            "Cori cycle: Lactate (muscle) → Glucose (liver)",
            "Alanine cycle: Alanine (muscle) → Glucose (liver)",
        ],
        "Pyruvate carboxylase requires biotin; activated by acetyl-CoA",
        "Clinical: PEPCK deficiency → hypoglycemia, lactic acidosis in neonates"
    ),
    (
        6, "Beta-Oxidation of Fatty Acids",
        [
            "Occurs in mitochondrial matrix; requires carnitine shuttle",
            "Each cycle removes 2C as Acetyl-CoA; yields 1 FADH2 + 1 NADH",
            "Palmitoyl-CoA (16C): 7 cycles → 8 Acetyl-CoA; net 129 ATP",
            "Rate-limiting: Carnitine acyltransferase I (inhibited by malonyl-CoA)",
            "Odd-chain FA → Propionyl-CoA → Succinyl-CoA (requires B12, biotin)",
        ],
        "Malonyl-CoA inhibits CAT-I: fed state blocks FA oxidation",
        "Clinical: MCAD deficiency → hypoketotic hypoglycemia; fatal without treatment"
    ),
    (
        7, "Ketone Body Metabolism",
        [
            "Formed in liver mitochondria from Acetyl-CoA during starvation/DM",
            "3 ketone bodies: Acetoacetate, β-hydroxybutyrate, Acetone",
            "Key enzyme for synthesis: HMG-CoA synthase (mitochondrial)",
            "Utilization: liver cannot use ketones (lacks succinyl-CoA transferase)",
            "Brain uses ketones during prolonged starvation (50% of energy)",
        ],
        "HMG-CoA synthase = rate-limiting for ketogenesis",
        "Clinical: DKA → fruity breath (acetone), high anion gap metabolic acidosis"
    ),
    (
        8, "Cholesterol Synthesis & Regulation",
        [
            "Occurs in cytoplasm/ER; 30 steps from Acetyl-CoA",
            "Rate-limiting enzyme: HMG-CoA reductase",
            "Key intermediate: Mevalonate → Squalene → Lanosterol → Cholesterol",
            "Regulation: insulin↑ (activates reductase); glucagon↓; statins inhibit HMG-CoA reductase",
            "Bile acids: primary (cholate, chenodeoxycholate), secondary (deoxycholate, lithocholate)",
        ],
        "HMG-CoA reductase = rate-limiting; STATINS block this enzyme",
        "Clinical: Familial hypercholesterolemia = LDL receptor defect → MI risk"
    ),
    (
        9, "Lipoprotein Metabolism",
        [
            "Chylomicrons: dietary lipids (intestine) → tissues; apoB-48",
            "VLDL: endogenous lipids (liver) → tissues; apoB-100",
            "IDL → LDL: delivers cholesterol to peripheral tissues",
            "HDL: reverse cholesterol transport (anti-atherogenic); apoA-I",
            "Key enzymes: LPL (hydrolyzes TG in chylomicrons/VLDL), LCAT, CETP",
        ],
        "HDL = 'good'; LDL = 'bad'; LPL activated by apoC-II",
        "Clinical: LPL deficiency → hyperchylomicronemia, pancreatitis, eruptive xanthomas"
    ),
    (
        10, "Urea Cycle",
        [
            "5 steps; partly mitochondrial, partly cytoplasmic",
            "Enzymes: CPS-I (mito), OTC (mito), AS, AL, Arginase (cyto)",
            "Net: 2 NH3 + CO2 → Urea + H2O (consumes 4 ATP)",
            "CPS-I is rate-limiting; activated by N-acetylglutamate (NAG)",
            "Fumarate links urea cycle to TCA cycle",
        ],
        "CPS-I deficiency = most severe urea cycle disorder",
        "Clinical: Hyperammonemia → cerebral edema, encephalopathy; OTC deficiency = X-linked"
    ),
    (
        11, "Amino Acid Metabolism - Key Disorders",
        [
            "PKU: Phe hydroxylase deficiency → Phe↑ → musty odour, intellectual disability",
            "Alkaptonuria: Homogentisate oxidase deficiency → HGA in urine (turns black)",
            "Albinism: Tyrosinase deficiency → no melanin → photosensitivity",
            "Maple Syrup Urine Disease: BCAA aminotransferase deficiency → leucine↑",
            "Homocystinuria: Cystathionine β-synthase deficiency → lens dislocation, DVT",
        ],
        "PKU: restrict Phe diet; supplement tyrosine",
        "Clinical: Screening at birth (Guthrie test) detects PKU, MSUD, homocystinuria"
    ),
    (
        12, "Heme Synthesis & Porphyrias",
        [
            "Starts in mitochondria: Succinyl-CoA + Glycine → ALA (ALA synthase = rate-limiting)",
            "ALA → Porphobilinogen → Uroporphyrinogen → Protoporphyrin IX → Heme",
            "Heme regulates its own synthesis (feedback inhibits ALA synthase)",
            "ALA synthase requires Pyridoxal Phosphate (B6)",
            "Lead inhibits ALA dehydratase & Ferrochelatase",
        ],
        "ALA synthase = rate-limiting; induced by drugs (barbiturates), AIP",
        "Clinical: Lead poisoning → basophilic stippling; AIP → abdominal pain, neuropsychiatric"
    ),
    (
        13, "Bilirubin Metabolism & Jaundice",
        [
            "Heme → Biliverdin → Unconjugated bilirubin (UCB, water-insoluble)",
            "UCB bound to albumin → liver → conjugated with glucuronic acid (CB)",
            "Conjugated bilirubin → bile → gut → Urobilinogen → Urobilin (stool/urine)",
            "Pre-hepatic jaundice: UCB↑ (hemolysis); Hepatic: both↑; Post-hepatic: CB↑",
            "Crigler-Najjar: UGT deficiency; Gilbert: mild UGT deficiency (benign)",
        ],
        "Kernicterus: UCB deposits in brain of neonates → neurological damage",
        "Clinical: Dubin-Johnson = CB↑ (conjugation intact, excretion impaired); black liver"
    ),
    (
        14, "DNA Replication",
        [
            "Semi-conservative; 5'→3' synthesis only",
            "Key enzymes: Helicase (unwinds), Primase (RNA primer), DNA Pol III (synthesis), Pol I (removes primer), Ligase (seals nicks)",
            "Leading strand: continuous; Lagging strand: Okazaki fragments",
            "Topoisomerases prevent supercoiling (target of fluoroquinolones)",
            "Eukaryotes: multiple origins of replication; uses DNA Pol α, δ, ε",
        ],
        "DNA Pol III = main replicating enzyme (prokaryotes); has proofreading (3'→5' exonuclease)",
        "Clinical: Defects in Nucleotide Excision Repair → Xeroderma pigmentosum"
    ),
    (
        15, "Transcription & Translation",
        [
            "Transcription: DNA → mRNA; enzyme = RNA Pol II (mRNA in eukaryotes)",
            "mRNA processing: 5' capping, 3' poly-A tail, splicing (remove introns)",
            "Translation: mRNA → Protein; ribosomes (70S prokaryote, 80S eukaryote)",
            "Codons: AUG = start (Met); UAA, UAG, UGA = stop codons",
            "Aminoacyl-tRNA synthetase charges tRNA; uses 2 ATP equivalent",
        ],
        "mRNA: 5'cap-UTR-AUG-ORF-STOP-UTR-poly(A)-3'",
        "Clinical: Aminoglycosides target 30S (misreading); Chloramphenicol targets 50S (peptidyl transferase)"
    ),
    (
        16, "Vitamins - Fat Soluble (A, D, E, K)",
        [
            "Vit A (Retinol): vision (rhodopsin), epithelial integrity; deficiency = night blindness, xerophthalmia",
            "Vit D (Calcitriol): Ca²⁺/PO4 absorption; deficiency = rickets (children), osteomalacia (adults)",
            "Vit E (Tocopherol): antioxidant (protects PUFA); deficiency = hemolytic anemia, spinocerebellar atax",
            "Vit K (Phylloquinone): clotting factors II, VII, IX, X; deficiency = bleeding (prolonged PT)",
            "All stored in liver/adipose; toxicity possible (A & D especially)",
        ],
        "Vit D: Skin→25-OH (liver)→1,25-(OH)2D3 (kidney, active form)",
        "Clinical: Vit K deficiency in newborns → hemorrhagic disease; treated with IM Vit K at birth"
    ),
    (
        17, "Vitamins - Water Soluble (B-complex & C)",
        [
            "B1 (Thiamine/TPP): pyruvate DH, α-KG DH, transketolase; deficiency = Beriberi, Wernicke's",
            "B2 (Riboflavin/FAD,FMN): electron carrier; deficiency = cheilosis, corneal vascularization",
            "B3 (Niacin/NAD+): energy metabolism; deficiency = Pellagra (4Ds: Dermatitis, Diarrhea, Dementia, Death)",
            "B6 (PLP): transamination, decarboxylation, heme synthesis; deficiency = sideroblastic anemia",
            "B12 (Cobalamin): myelin synthesis, odd-chain FA, one-carbon metabolism; deficiency = megaloblastic anemia + subacute combined degeneration",
            "Folate: DNA synthesis (thymidylate); deficiency = megaloblastic anemia (NO neuro symptoms)",
            "Vit C (Ascorbic acid): collagen synthesis (hydroxylation of Pro/Lys); deficiency = Scurvy",
        ],
        "B12 vs Folate deficiency: both cause megaloblastic anemia; only B12 causes neuro symptoms",
        "Clinical: Isoniazid (TB drug) → B6 deficiency; give pyridoxine supplement"
    ),
    (
        18, "Iron Metabolism",
        [
            "Absorbed as Fe²⁺ in duodenum via DMT-1; Vit C enhances absorption",
            "Transported in plasma bound to Transferrin (Fe³⁺ form)",
            "Stored as Ferritin (labile) and Hemosiderin (insoluble)",
            "Hepcidin: master regulator - blocks ferroportin → ↓iron release",
            "Serum iron↑, TIBC↓, Ferritin↑ = Iron overload; Iron def = reverse pattern",
        ],
        "Ferritin = acute phase reactant; high in inflammation even with low iron",
        "Clinical: Iron deficiency anemia: microcytic hypochromic RBCs, pica, spoon nails (koilonychia)"
    ),
    (
        19, "Enzyme Kinetics",
        [
            "Michaelis-Menten: V = Vmax[S] / (Km + [S])",
            "Km = [S] at ½ Vmax; low Km = high affinity",
            "Lineweaver-Burk plot: 1/V vs 1/[S]; x-intercept = -1/Km, y-intercept = 1/Vmax",
            "Competitive inhibition: Km↑, Vmax unchanged (reversible by ↑[S])",
            "Non-competitive: Vmax↓, Km unchanged (cannot overcome by ↑[S])",
            "Uncompetitive: both Km↓ and Vmax↓",
        ],
        "Isoenzymes: same reaction, different molecular forms; tissue-specific",
        "Clinical: LDH-1 (heart) > LDH-2 in MI; CK-MB elevated in MI; Troponin = gold standard"
    ),
    (
        20, "Recombinant DNA Technology",
        [
            "Restriction endonucleases: cut DNA at palindromic sequences → sticky/blunt ends",
            "PCR: denaturation → annealing → extension (Taq polymerase); amplifies specific DNA",
            "Southern blot: DNA probe; Northern blot: RNA probe; Western blot: protein (antibody)",
            "DNA library: genomic (all DNA) vs cDNA (from mRNA via reverse transcriptase)",
            "CRISPR-Cas9: gene editing using guide RNA + Cas9 endonuclease",
        ],
        "Mnemonic: SNoW DRoP – S=DNA, N=RNA, W=protein; D=DNA probe, R=RNA probe, P=protein(antibody)",
        "Clinical: PCR used for HIV viral load, COVID-19 diagnosis, genetic disease detection"
    ),
]

# ════════════════════════════════════════════════════════════════════
# PAGE TEMPLATE (background banner)
# ════════════════════════════════════════════════════════════════════
def draw_bg(canvas, doc):
    w, h = A4
    # top banner
    canvas.setFillColor(DARK_BLUE)
    canvas.rect(0, h - 1.1*cm, w, 1.1*cm, fill=1, stroke=0)
    # bottom bar
    canvas.setFillColor(DARK_BLUE)
    canvas.rect(0, 0, w, 0.7*cm, fill=1, stroke=0)
    # footer text
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(w/2, 0.22*cm, "KNRUHS 1st MBBS Biochemistry Cheat Sheet  |  For Exam Preparation Only")
    # page number
    canvas.drawRightString(w - 1.5*cm, 0.22*cm, f"Page {doc.page}")


# ════════════════════════════════════════════════════════════════════
# BUILD CONTENT
# ════════════════════════════════════════════════════════════════════
story = []

# ── COVER SECTION ──────────────────────────────────────────────────
cover_table_data = [[
    Paragraph("KNRUHS 1st MBBS", cover_title),
],[
    Paragraph("BIOCHEMISTRY CHEAT SHEET", cover_title),
],[
    Paragraph("Top 20 Most Repeated Topics | Exam Quick Reference", cover_sub),
],[
    Paragraph("Paper I & Paper II  •  Last 5 Exams Pattern  •  2021–2025", cover_note),
]]

cover_bg = Table(cover_table_data, colWidths=[doc.width])
cover_bg.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ("LEFTPADDING",   (0,0), (-1,-1), 12),
    ("RIGHTPADDING",  (0,0), (-1,-1), 12),
    ("ROUNDEDCORNERS", (0,0), (-1,-1), [8, 8, 8, 8]),
]))

story.append(cover_bg)
story.append(Spacer(1, 0.35*cm))

# ── LEGEND BAR ─────────────────────────────────────────────────────
legend_data = [[
    Paragraph("<b>🔑 Key Point</b>", S("Normal", fontSize=8, textColor=GREEN)),
    Paragraph("<b>🏥 Clinical Note</b>", S("Normal", fontSize=8, textColor=RED)),
    Paragraph("<b>★ High Priority Topic</b>", S("Normal", fontSize=8, textColor=DARK_BLUE)),
]]
legend_table = Table(legend_data, colWidths=[doc.width/3]*3)
legend_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
    ("BOX", (0,0), (-1,-1), 0.5, MED_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
]))
story.append(legend_table)
story.append(Spacer(1, 0.3*cm))

# ── TOPIC CARDS (2 columns) ─────────────────────────────────────────
COL_W = (doc.width - 0.4*cm) / 2

def make_topic_card(num, title, bullets, keypoint, clinical):
    """Build a single topic card as a Table (for background colour)."""
    inner = []

    # Header row
    hdr = Table(
        [[Paragraph(f"#{num}  {title}", sec_heading)]],
        colWidths=[COL_W - 0.2*cm]
    )
    hdr.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), MED_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
        ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ]))
    inner.append(hdr)

    # Bullets
    for b in bullets:
        inner.append(Paragraph(f"• {b}", bullet_style))

    # Key point
    inner.append(Spacer(1, 2))
    inner.append(Paragraph(f"🔑 {keypoint}", key_point))

    # Clinical note
    inner.append(Paragraph(f"🏥 {clinical}", clinical_style))
    inner.append(Spacer(1, 4))

    # Wrap all in a card-style Table
    card = Table([[inner_item] for inner_item in inner], colWidths=[COL_W - 0.2*cm])
    card.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
        ("TOPPADDING",    (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ]))

    outer = Table([[card]], colWidths=[COL_W])
    outer.setStyle(TableStyle([
        ("BOX", (0,0), (-1,-1), 0.8, MED_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING",   (0,0), (-1,-1), 0),
        ("RIGHTPADDING",  (0,0), (-1,-1), 0),
    ]))
    return outer


# Pair up topics into 2-column rows
def build_row(t1, t2=None):
    card1 = make_topic_card(*t1)
    if t2:
        card2 = make_topic_card(*t2)
        row = Table([[card1, Spacer(0.4*cm, 1), card2]],
                    colWidths=[COL_W, 0.4*cm, COL_W])
    else:
        row = Table([[card1, Spacer(0.4*cm, 1), Spacer(COL_W, 1)]],
                    colWidths=[COL_W, 0.4*cm, COL_W])
    row.setStyle(TableStyle([
        ("VALIGN", (0,0), (-1,-1), "TOP"),
        ("TOPPADDING",    (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING",   (0,0), (-1,-1), 0),
        ("RIGHTPADDING",  (0,0), (-1,-1), 0),
    ]))
    return row

for i in range(0, len(TOPICS), 2):
    t1 = TOPICS[i]
    t2 = TOPICS[i+1] if i+1 < len(TOPICS) else None
    story.append(build_row(t1, t2))
    story.append(Spacer(1, 0.25*cm))

# ── QUICK REFERENCE TABLE ───────────────────────────────────────────
story.append(PageBreak())
story.append(Spacer(1, 0.3*cm))

qr_hdr = Table(
    [[Paragraph("QUICK REFERENCE: High-Yield Points at a Glance", sec_heading)]],
    colWidths=[doc.width]
)
qr_hdr.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
]))
story.append(qr_hdr)
story.append(Spacer(1, 0.2*cm))

qr_style_h = S("Normal", fontSize=8.5, textColor=WHITE, fontName="Helvetica-Bold")
qr_style_b = S("Normal", fontSize=8, textColor=DARK_BLUE)

qr_data = [
    [Paragraph("Topic", qr_style_h), Paragraph("Rate-Limiting Enzyme", qr_style_h),
     Paragraph("Key Deficiency / Disease", qr_style_h), Paragraph("Clinical Marker", qr_style_h)],
    ["Glycolysis", "PFK-1", "Tarui disease (PFK-1)", "Lactate↑"],
    ["TCA cycle", "Isocitrate DH", "Wernicke's (B1 def)", "α-KG DH requires TPP"],
    ["HMP shunt", "G6PD", "G6PD deficiency", "Heinz bodies, Bite cells"],
    ["Glycogenesis", "Glycogen synthase", "Type 0 GSD", "Hypoglycemia postprandially"],
    ["Glycogenolysis", "Glycogen phosphorylase", "McArdle (Type V)", "Myoglobinuria"],
    ["Gluconeogenesis", "PEPCK / F1,6-BPase", "Von Gierke (Type I)", "Lactic acidosis"],
    ["Fatty acid oxidation", "CAT-I (carnitine shuttle)", "MCAD deficiency", "Hypoketotic hypoglycemia"],
    ["Ketogenesis", "HMG-CoA synthase", "DKA", "β-OHB in blood/urine"],
    ["Cholesterol synthesis", "HMG-CoA reductase", "Familial hypercholesterolemia", "LDL-receptor absent"],
    ["Urea cycle", "CPS-I", "OTC deficiency (X-linked)", "NH3↑, Orotic acid↑ in urine"],
    ["Heme synthesis", "ALA synthase (δ-ALA-S)", "Lead poisoning / AIP", "ALA↑ in urine"],
    ["DNA replication", "DNA Pol III (prok)", "XP (NER defect)", "Dipyrimidine dimers"],
    ["Protein synthesis", "Ribosome (80S euk)", "Aminoglycoside toxicity", "Misreading 30S"],
]

# Convert to Paragraph
qr_formatted = []
for i, row in enumerate(qr_data):
    if i == 0:
        qr_formatted.append(row)
    else:
        qr_formatted.append([Paragraph(str(c), qr_style_b) for c in row])

qr_table = Table(qr_formatted, colWidths=[doc.width*0.22, doc.width*0.22, doc.width*0.32, doc.width*0.24])
qr_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), MED_BLUE),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, LIGHT_BLUE]),
    ("GRID", (0,0), (-1,-1), 0.3, colors.HexColor("#aaaaaa")),
    ("FONTSIZE", (0,0), (-1,-1), 8),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING",   (0,0), (-1,-1), 5),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
]))
story.append(qr_table)
story.append(Spacer(1, 0.4*cm))

# ── MNEMONICS BOX ──────────────────────────────────────────────────
mn_data = [
    [Paragraph("ESSENTIAL MNEMONICS", S("Normal", fontSize=10, textColor=WHITE,
               fontName="Helvetica-Bold", alignment=TA_CENTER))],
    [Paragraph(
        "<b>Pellagra (B3 def):</b> 4 D's – Dermatitis, Diarrhea, Dementia, Death<br/>"
        "<b>Urea cycle enzymes:</b> Cindy Often Appears Arrogant &amp; Lazy (CPS-I, OTC, AS, AL, Arginase)<br/>"
        "<b>Fat-soluble vitamins:</b> ADEK – All Dogs Eat Kibble<br/>"
        "<b>Blot methods (SNoW DRoP):</b> Southern=DNA, Northern=RNA, Western=Protein<br/>"
        "<b>Glycogen storage:</b> Very Poor Carb Metabolism (Von Gierke, Pompe, Cori, McArdle)<br/>"
        "<b>Jaundice types:</b> Pre-hepatic (UCB↑) | Hepatic (both↑) | Post-hepatic (CB↑, pale stool, dark urine)",
        S("Normal", fontSize=8.5, textColor=DARK_BLUE, leading=14)
    )],
]
mn_table = Table(mn_data, colWidths=[doc.width])
mn_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (0,0), ACCENT),
    ("BACKGROUND", (0,1), (0,1), ACCENT_LIGHT),
    ("BOX", (0,0), (-1,-1), 1, ACCENT),
    ("TOPPADDING",    (0,0), (-1,-1), 7),
    ("BOTTOMPADDING", (0,0), (-1,-1), 7),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
    ("RIGHTPADDING",  (0,0), (-1,-1), 10),
]))
story.append(mn_table)
story.append(Spacer(1, 0.3*cm))

# disclaimer
story.append(Paragraph(
    "★ This cheat sheet covers the most frequently tested topics in KNRUHS 1st MBBS Biochemistry. "
    "Always cross-reference with your textbook (Harper's / Lippincott / Devlin). "
    "Prepared for exam revision purposes only.",
    S("Normal", fontSize=7.5, textColor=colors.HexColor("#555555"),
      alignment=TA_CENTER, leading=11)
))

# ════════════════════════════════════════════════════════════════════
doc.build(story, onFirstPage=draw_bg, onLaterPages=draw_bg)
print("PDF created successfully:", OUTPUT)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, PageBreak
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT

import os
os.makedirs("/tmp/workspace/knruhs-anatomy", exist_ok=True)

OUTPUT = "/tmp/workspace/knruhs-anatomy/KNRUHS_Anatomy_CheatSheet.pdf"

doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    rightMargin=1.5*cm, leftMargin=1.5*cm,
    topMargin=1.8*cm, bottomMargin=1.8*cm,
)

# Colour palette
DARK      = colors.HexColor("#1a3a2c")
MED       = colors.HexColor("#2e7d52")
LIGHT_BG  = colors.HexColor("#d6f0e4")
ACCENT    = colors.HexColor("#e88020")
ACC_LIGHT = colors.HexColor("#fff4dc")
RED       = colors.HexColor("#b03030")
GREEN     = colors.HexColor("#1a6e38")
GREY_BG   = colors.HexColor("#f4f8f5")
WHITE     = colors.white

styles = getSampleStyleSheet()
def S(name, **kw):
    base = styles.get(name, styles["Normal"])
    return ParagraphStyle(name+"_c"+str(id(kw)), parent=base, **kw)

cover_title  = S("Title",   fontSize=26, textColor=WHITE,   alignment=TA_CENTER, leading=32)
cover_sub    = S("Normal",  fontSize=13, textColor=ACCENT,  alignment=TA_CENTER, leading=18)
cover_note   = S("Normal",  fontSize=9,  textColor=colors.HexColor("#cceedc"), alignment=TA_CENTER)
sec_heading  = S("Heading1",fontSize=11, textColor=WHITE,   alignment=TA_LEFT,  leading=14)
bullet_style = S("Normal",  fontSize=8.2,textColor=colors.HexColor("#222222"), alignment=TA_LEFT, leading=11.5, leftIndent=10)
key_point    = S("Normal",  fontSize=8,  textColor=GREEN,   fontName="Helvetica-Bold", alignment=TA_LEFT, leading=11)
clin_style   = S("Normal",  fontSize=8,  textColor=RED,     fontName="Helvetica-BoldOblique", alignment=TA_LEFT, leading=11)
qr_hdr_s     = S("Normal",  fontSize=8.5,textColor=WHITE,   fontName="Helvetica-Bold")
qr_body_s    = S("Normal",  fontSize=8,  textColor=DARK)

TOPICS = [
    (1,"Brachial Plexus",
     ["Roots: C5-T1; formed in posterior triangle of neck",
      "5 terminals: Musculocutaneous, Median, Ulnar, Radial, Axillary",
      "Trunks: Upper (C5,C6), Middle (C7), Lower (C8,T1)",
      "Divisions → Cords (Lateral, Posterior, Medial) → Branches",
      "Erb's palsy: C5,C6 injury → waiter's tip; Klumpke: C8,T1 → claw hand"],
     "Lateral cord + Medial cord → Median nerve (M-shape on front)",
     "Clinical: Erb's palsy = birth injury (forceps); Klumpke = apical lung tumour (Pancoast)"),
    (2,"Femoral Triangle",
     ["Boundaries: Inguinal lig (sup), Sartorius (lat), Adductor longus (med)",
      "Floor: Iliopsoas (lat), Pectineus (med)",
      "Contents (lateral→medial): NAVEL – Nerve, Artery, Vein, Empty space, Lymphatics",
      "Femoral sheath contains: FA, FV, femoral canal (lymphatics + Cloquet node)",
      "Femoral nerve is OUTSIDE the femoral sheath"],
     "Mnemonic NAVEL: N=nerve, A=artery, V=vein, E=empty, L=lymphatics",
     "Clinical: Femoral hernia passes through femoral canal; more common in women"),
    (3,"Cubital Fossa",
     ["Boundaries: Pronator teres (med), Brachioradialis (lat), line joining epicondyles (sup)",
      "Roof: deep fascia + bicipital aponeurosis",
      "Floor: Brachialis + Supinator",
      "Contents (med→lat): Median nerve, Brachial artery, Biceps tendon, Radial nerve",
      "Mnemonic: My Beer Brings Relaxation (Median, Brachial, Biceps, Radial)"],
     "Biceps tendon is the central landmark",
     "Clinical: Supracondylar fracture → anterior interosseous nerve injury (loss of pinch)"),
    (4,"Nerve Injuries of Upper Limb",
     ["Radial nerve: Saturday night palsy → wrist drop; no sensory loss over back of hand usually",
      "Ulnar nerve: medial epicondyle injury → claw hand (4th,5th fingers)",
      "Median nerve: carpal tunnel → ape hand, loss of opposition, thenar wasting",
      "Axillary nerve: surgical neck humerus fx → deltoid paralysis, loss over 'regimental badge' area",
      "Long thoracic nerve (C5-7): serratus anterior → winged scapula"],
     "Median nerve = 'labourer's nerve'; Ulnar = 'musician's nerve'",
     "Clinical: Carpal tunnel syndrome = most common nerve entrapathy; Tinel & Phalen test positive"),
    (5,"Heart - Conducting System",
     ["SA node → AV node → Bundle of His → L+R bundle branches → Purkinje fibres",
      "SA node: right atrium, near SVC; pacemaker (60-100 bpm)",
      "AV node: interatrial septum; delays impulse 0.1 sec",
      "Right coronary artery supplies SA node (60%) and AV node (80%)",
      "Bachmann's bundle: interatrial conduction"],
     "SA node = dominant pacemaker; automaticity due to If (funny current)",
     "Clinical: RCA occlusion → SA/AV node ischaemia → bradycardia, heart block"),
    (6,"Coronary Arteries",
     ["LCA: Left main → LAD (anterior IVS, anterior LV) + LCx (lateral/posterior LV)",
      "RCA: SA node, AV node, posterior IVS (80% dominant), RV",
      "Dominant coronary: gives posterior descending artery (PDA)",
      "Right dominant in 80%, left dominant in 10%, co-dominant 10%",
      "Coronary arteries are END arteries (anastomoses are functional, not effective)"],
     "LAD = 'widow maker'; most common site of MI",
     "Clinical: STEMI territories: LAD=anterior, RCA=inferior, LCx=lateral"),
    (7,"Lungs & Pleura",
     ["Right lung: 3 lobes (upper, middle, lower); 10 bronchopulmonary segments",
      "Left lung: 2 lobes (upper+lingula, lower); 8-9 bronchopulmonary segments",
      "Hilum: bronchus (posterior/superior), pulmonary artery (anterior/superior), veins (inferior)",
      "Pleura: visceral (lung surface) + parietal (chest wall); pleural cavity = potential space",
      "Oblique fissure: both lungs (T2-6); Horizontal fissure: right lung only (4th costal cartilage)"],
     "Right bronchus: wider, shorter, more vertical → foreign bodies more common",
     "Clinical: Pleural effusion: blunting of costophrenic angle on X-ray (300 mL needed)"),
    (8,"Liver - Segments & Porta Hepatis",
     ["8 Couinaud segments; functionally divided by hepatic veins",
      "Porta hepatis: portal vein (posterior), hepatic artery (left), bile duct (right) – 'Rule of 2 arteries'",
      "Portal triad: portal vein, hepatic artery, bile ductule",
      "Blood supply: Portal vein 75% (nutrition), Hepatic artery 25% (oxygen)",
      "Bare area: not covered by peritoneum; in contact with diaphragm"],
     "Porta hepatis structures: mnemonic 'Hate Borders People' (Hepatic artery, Bile duct, Portal vein) L to R",
     "Clinical: Portal hypertension → portosystemic anastomoses → varices (oesophageal, haemorrhoidal, caput medusae)"),
    (9,"Kidney - Relations & Hilum",
     ["Right kidney lower than left (liver pushes it down)",
      "Relations anteriorly: Right – liver, duodenum, hepatic flexure; Left – spleen, pancreas, jejunum",
      "Hilum: vein (anterior), artery (middle), pelvis (posterior) – VAP",
      "Nephron: Glomerulus → PCT → LoH → DCT → collecting duct",
      "Renal fascia (Gerota's fascia) encloses kidney + suprarenal gland"],
     "Renal hilum at L1 level; right renal vein shorter → more DVT risk",
     "Clinical: Horseshoe kidney → fused at lower poles → lies in front of aorta; prone to pelviureteric junction obstruction"),
    (10,"Vertebral Column - Curvatures & Joints",
     ["Primary curvatures (fetal): thoracic kyphosis + sacral kyphosis (concave anteriorly)",
      "Secondary curvatures (postnatal): cervical lordosis (3 months) + lumbar lordosis (walking)",
      "Intervertebral disc: nucleus pulposus (central, gelatinous) + annulus fibrosus (outer rings)",
      "L4-L5, L5-S1: most common sites of disc herniation",
      "Ligaments: anterior/posterior longitudinal, ligamentum flavum, supraspinous, interspinous"],
     "Nucleus pulposus: remnant of notochord; herniates posterolaterally",
     "Clinical: L4-5 disc → L5 root → foot drop; L5-S1 → S1 root → loss of ankle jerk"),
    (11,"Diaphragm - Openings",
     ["T8: IVC + right phrenic nerve (caval opening - most anterior)",
      "T10: Oesophagus + vagus nerve (left anterior, right posterior) + oesophageal branches",
      "T12: Aorta + thoracic duct + azygos vein (most posterior)",
      "Mnemonic: I 8 (ate) 10 eggs AT 12 (I=IVC T8, E=oesophagus T10, A=aorta T12)",
      "Motor supply: phrenic nerve (C3,4,5); Sensory: phrenic (central) + intercostal (peripheral)"],
     "C3,4,5 keeps the diaphragm alive",
     "Clinical: Diaphragmatic hernia: congenital (Bochdalek-posterior left) → bowel in thorax → respiratory distress"),
    (12,"Portal Venous System",
     ["Portal vein formed by: Superior mesenteric vein + Splenic vein (behind neck of pancreas)",
      "Tributaries: SMV, splenic vein, IMV, left gastric, right gastric, cystic veins",
      "Normal portal pressure: 5-10 mmHg; hypertension > 12 mmHg",
      "Portosystemic anastomoses: oesophageal (oesophageal varices), rectal (haemorrhoids), paraumbilical (caput medusae), retroperitoneal",
      "Portal vein drains all GI tract (stomach to upper rectum), spleen, pancreas"],
     "Portal vein = no valves; flow is pressure-dependent",
     "Clinical: Liver cirrhosis → portal HTN → oesophageal varices → upper GI bleed (haematemesis)"),
    (13,"Bony Pelvis & Pelvic Floor",
     ["Pelvic inlet (brim): sacral promontory → arcuate line → pubic symphysis",
      "Pelvic outlet: pubic arch + ischial tuberosities + coccyx",
      "Pelvic floor (levator ani): puborectalis, pubococcygeus, iliococcygeus",
      "True vs False pelvis: divided by pelvic brim; false pelvis = lower abdomen",
      "Female pelvis: wider, shallower, gynecoid (oval inlet); Male: narrower, android (heart-shaped)"],
     "Levator ani nerve: S3,S4 (nerve to levator ani) + inferior rectal nerve",
     "Clinical: Pelvic floor damage in childbirth → stress incontinence, uterine prolapse"),
    (14,"Cranial Nerves - Summary",
     ["CN I (Olfactory): smell; CN II (Optic): vision; CN III (Oculomotor): most EOM + pupil constriction",
      "CN V (Trigeminal): facial sensation + mastication; CN VII (Facial): facial expression + taste anterior 2/3 tongue",
      "CN VIII (Vestibulocochlear): hearing + balance; CN IX (Glossopharyngeal): taste posterior 1/3 + gag reflex",
      "CN X (Vagus): parasympathetic to thorax/abdomen; CN XI (Accessory): SCM + trapezius",
      "CN XII (Hypoglossal): tongue movements"],
     "Mnemonic: Oh Oh Oh To Touch And Feel Very Good Velvet AH (CN I-XII)",
     "Clinical: CN III palsy = ptosis + 'down and out' eye + dilated pupil (surgical 3rd nerve palsy)"),
    (15,"Spinal Cord Tracts",
     ["Sensory (ascending): Dorsal columns (fine touch, proprioception, vibration) – ipsilateral",
      "Spinothalamic tract: pain, temperature, crude touch – crosses at spinal level (contralateral)",
      "Motor (descending): Corticospinal tract – crosses at medulla (pyramidal decussation)",
      "UMN lesion: spasticity, hyperreflexia, Babinski positive, no wasting",
      "LMN lesion: flaccidity, hyporeflexia, fasciculations, wasting"],
     "Dorsal columns: vibration & proprioception; Spinothalamic: pain & temperature",
     "Clinical: Brown-Sequard syndrome: ipsilateral motor + proprioception loss; contralateral pain/temp loss"),
    (16,"Axilla - Contents & Walls",
     ["Apex: 1st rib + clavicle + scapula; Base: skin of axilla",
      "Walls: Anterior (pectoralis major/minor), Posterior (subscapularis, teres major, latissimus dorsi)",
      "Contents: Axillary artery (3 parts relative to pectoralis minor), axillary vein, brachial plexus cords, lymph nodes, fat",
      "Axillary lymph nodes: 5 groups (anterior/pectoral, posterior/subscapular, lateral, central, apical)",
      "Apical group drains to subclavian lymph trunk"],
     "Axillary artery: 3 parts - 1 branch, 2 branches, 3 branches (1-2-3 rule)",
     "Clinical: Axillary node clearance in breast cancer → lymphoedema of arm"),
    (17,"Stomach - Blood Supply & Relations",
     ["Lesser curvature: left gastric artery (celiac trunk) + right gastric artery (hepatic artery)",
      "Greater curvature: left gastroepiploic (splenic) + right gastroepiploic (gastroduodenal)",
      "Fundus: short gastric arteries (from splenic artery)",
      "Relations anteriorly: left lobe liver, anterior abdominal wall; Posteriorly: lesser sac, pancreas",
      "Pyloric sphincter: at L1; marks junction of stomach and duodenum"],
     "Lesser omentum connects stomach/duodenum to liver; greater omentum hangs from greater curvature",
     "Clinical: Peptic ulcer: posterior duodenal ulcer erodes gastroduodenal artery → massive haemorrhage"),
    (18,"Eye - Anatomy",
     ["Layers: fibrous (sclera/cornea), vascular (choroid/ciliary body/iris), nervous (retina)",
      "Aqueous humour: produced by ciliary body, drains via Canal of Schlemm (trabecular meshwork)",
      "Extraocular muscles (6): 4 recti + 2 obliques; CN III supplies all except lateral rectus (VI) and superior oblique (IV)",
      "Visual pathway: retina → optic nerve → optic chiasm → optic tract → LGN → optic radiation → occipital cortex",
      "Nasal fibres cross at chiasm; temporal fibres are ipsilateral"],
     "Mnemonic SO4 LR6 rest 3 (Superior Oblique CN4, Lateral Rectus CN6, rest CN3)",
     "Clinical: Glaucoma = raised IOP due to impaired aqueous drainage; optic disc cupping on fundoscopy"),
    (19,"Lymphatic Drainage - Clinical Anatomy",
     ["Head/neck: deep cervical nodes (jugulodigastric node = 'tonsillar node')",
      "Breast: axillary (75%), internal mammary nodes; upper outer quadrant most common cancer site",
      "Upper limb: axillary nodes; Lower limb: inguinal nodes (superficial + deep)",
      "GI tract above umbilicus: celiac nodes; below: mesenteric, iliac nodes",
      "Right lymphatic duct: right head/neck/arm/right thorax; Thoracic duct: rest of body"],
     "Thoracic duct: longest lymph vessel; enters at junction of left subclavian + internal jugular veins",
     "Clinical: Virchow's node (left supraclavicular) = metastasis from stomach/abdominal cancer (Troisier's sign)"),
    (20,"Histology - Epithelium & Connective Tissue",
     ["Simple squamous: lining of vessels (endothelium), alveoli, Bowman's capsule",
      "Simple cuboidal: kidney tubules, thyroid follicles, small ducts",
      "Simple columnar: GI tract (non-ciliated), uterine tube (ciliated)",
      "Stratified squamous: skin (keratinized), oral cavity/oesophagus/vagina (non-keratinized)",
      "Transitional (urothelium): ureter, bladder, renal pelvis"],
     "Pseudostratified columnar ciliated: respiratory tract (PSCC)",
     "Clinical: Barrett's oesophagus = metaplasia: squamous → columnar (acid reflux) → premalignant"),
]

def draw_bg(canvas, doc):
    w, h = A4
    canvas.setFillColor(DARK)
    canvas.rect(0, h-1.1*cm, w, 1.1*cm, fill=1, stroke=0)
    canvas.setFillColor(DARK)
    canvas.rect(0, 0, w, 0.7*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(w/2, 0.22*cm, "KNRUHS 1st MBBS Anatomy Cheat Sheet  |  For Exam Preparation Only")
    canvas.drawRightString(w-1.5*cm, 0.22*cm, f"Page {doc.page}")

story = []

# Cover
cover_data = [
    [Paragraph("KNRUHS 1st MBBS", cover_title)],
    [Paragraph("ANATOMY CHEAT SHEET", cover_title)],
    [Paragraph("Top 20 Most Repeated Topics | Exam Quick Reference", cover_sub)],
    [Paragraph("Paper I & Paper II  •  Last 5 Exams Pattern  •  2021–2025", cover_note)],
]
cover_t = Table(cover_data, colWidths=[doc.width])
cover_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK),
    ("TOPPADDING", (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ("LEFTPADDING", (0,0), (-1,-1), 12),
]))
story.append(cover_t)
story.append(Spacer(1, 0.3*cm))

legend_data = [[
    Paragraph("<b>🔑 Key Point</b>", S("Normal", fontSize=8, textColor=GREEN)),
    Paragraph("<b>🏥 Clinical Note</b>", S("Normal", fontSize=8, textColor=RED)),
    Paragraph("<b>★ High Priority Topic</b>", S("Normal", fontSize=8, textColor=DARK)),
]]
legend_t = Table(legend_data, colWidths=[doc.width/3]*3)
legend_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
    ("BOX", (0,0), (-1,-1), 0.5, MED),
    ("TOPPADDING", (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
]))
story.append(legend_t)
story.append(Spacer(1, 0.3*cm))

COL_W = (doc.width - 0.4*cm) / 2

def make_card(num, title, bullets, keypoint, clinical):
    inner = []
    hdr = Table([[Paragraph(f"#{num}  {title}", sec_heading)]], colWidths=[COL_W-0.2*cm])
    hdr.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), MED),
        ("TOPPADDING", (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING", (0,0), (-1,-1), 8),
    ]))
    inner.append(hdr)
    for b in bullets:
        inner.append(Paragraph(f"• {b}", bullet_style))
    inner.append(Spacer(1, 2))
    inner.append(Paragraph(f"🔑 {keypoint}", key_point))
    inner.append(Paragraph(f"🏥 {clinical}", clin_style))
    inner.append(Spacer(1, 4))
    card = Table([[i] for i in inner], colWidths=[COL_W-0.2*cm])
    card.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
        ("TOPPADDING", (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
        ("LEFTPADDING", (0,0), (-1,-1), 6),
        ("RIGHTPADDING", (0,0), (-1,-1), 4),
    ]))
    outer = Table([[card]], colWidths=[COL_W])
    outer.setStyle(TableStyle([
        ("BOX", (0,0), (-1,-1), 0.8, MED),
        ("TOPPADDING", (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ]))
    return outer

def build_row(t1, t2=None):
    c1 = make_card(*t1)
    if t2:
        c2 = make_card(*t2)
        row = Table([[c1, Spacer(0.4*cm,1), c2]], colWidths=[COL_W, 0.4*cm, COL_W])
    else:
        row = Table([[c1, Spacer(0.4*cm,1), Spacer(COL_W,1)]], colWidths=[COL_W, 0.4*cm, COL_W])
    row.setStyle(TableStyle([
        ("VALIGN", (0,0), (-1,-1), "TOP"),
        ("TOPPADDING", (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ]))
    return row

for i in range(0, len(TOPICS), 2):
    story.append(build_row(TOPICS[i], TOPICS[i+1] if i+1 < len(TOPICS) else None))
    story.append(Spacer(1, 0.25*cm))

# Quick Reference Table
story.append(PageBreak())
story.append(Spacer(1, 0.3*cm))
qr_hdr_t = Table([[Paragraph("QUICK REFERENCE: Anatomy High-Yield Points", sec_heading)]], colWidths=[doc.width])
qr_hdr_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
]))
story.append(qr_hdr_t)
story.append(Spacer(1, 0.2*cm))

qr_rows = [
    [Paragraph(h, qr_hdr_s) for h in ["Structure", "Key Landmark / Level", "Important Nerve/Vessel", "Clinical Condition"]],
    ["Femoral triangle", "Inguinal ligament (sup)", "Femoral nerve (outside sheath)", "Femoral hernia (women)"],
    ["Cubital fossa", "Biceps tendon (central)", "Median nerve (medial)", "Supracondylar fracture"],
    ["Diaphragm openings", "T8/T10/T12", "Phrenic nerve (C3,4,5)", "Hiatus hernia"],
    ["Brachial plexus", "C5–T1 roots", "Median, Ulnar, Radial, Axillary", "Erb's / Klumpke palsy"],
    ["Vertebral disc", "L4-5 / L5-S1 common", "L5 / S1 nerve roots", "Foot drop / loss ankle jerk"],
    ["Coronary arteries", "RCA 80% dominant", "LAD = anterior IVS", "Anterior MI (LAD)"],
    ["Portal vein", "Behind neck of pancreas", "SMV + Splenic vein join", "Oesophageal varices"],
    ["Kidney hilum", "L1 vertebral level", "VAP – Vein, Artery, Pelvis", "Renal calculi"],
    ["Visual pathway", "Optic chiasm (nasal cross)", "Optic radiation (temporal)", "Bitemporal hemianopia (pituitary)"],
    ["Thoracic duct", "T12–L2 cisterna chyli", "Drains into left SCV-IJV junction", "Chylothorax"],
]
qr_formatted = []
for i, row in enumerate(qr_rows):
    if i == 0:
        qr_formatted.append(row)
    else:
        qr_formatted.append([Paragraph(str(c), qr_body_s) for c in row])

qr_t = Table(qr_formatted, colWidths=[doc.width*0.22, doc.width*0.22, doc.width*0.3, doc.width*0.26])
qr_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), MED),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, colors.HexColor("#d6f0e4")]),
    ("GRID", (0,0), (-1,-1), 0.3, colors.HexColor("#aaaaaa")),
    ("FONTSIZE", (0,0), (-1,-1), 8),
    ("TOPPADDING", (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
]))
story.append(qr_t)
story.append(Spacer(1, 0.4*cm))

mn_data = [
    [Paragraph("ESSENTIAL ANATOMY MNEMONICS", S("Normal", fontSize=10, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER))],
    [Paragraph(
        "<b>Brachial plexus terminals:</b> My Muscles Are Really Useful (Musculocutaneous, Median, Axillary, Radial, Ulnar)<br/>"
        "<b>Femoral triangle contents:</b> NAVEL – Nerve, Artery, Vein, Empty space, Lymphatics (lateral → medial)<br/>"
        "<b>Cubital fossa:</b> My Beer Brings Relaxation (Median nerve, Brachial artery, Biceps tendon, Radial nerve)<br/>"
        "<b>Diaphragm openings:</b> I 8 (ate) 10 Eggs AT 12 (IVC=T8, Oesophagus=T10, Aorta=T12)<br/>"
        "<b>Cranial nerves:</b> Oh Oh Oh To Touch And Feel Very Good Velvet AH (CN I to XII)<br/>"
        "<b>EOM nerve supply:</b> SO4 LR6 rest 3 (Superior Oblique→CN4, Lateral Rectus→CN6, rest→CN3)",
        S("Normal", fontSize=8.5, textColor=DARK, leading=14)
    )],
]
mn_t = Table(mn_data, colWidths=[doc.width])
mn_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (0,0), ACCENT),
    ("BACKGROUND", (0,1), (0,1), ACC_LIGHT),
    ("BOX", (0,0), (-1,-1), 1, ACCENT),
    ("TOPPADDING", (0,0), (-1,-1), 7),
    ("BOTTOMPADDING", (0,0), (-1,-1), 7),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
    ("RIGHTPADDING", (0,0), (-1,-1), 10),
]))
story.append(mn_t)
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "★ Covers most frequently tested KNRUHS 1st MBBS Anatomy topics. Always reference Gray's Anatomy / BD Chaurasia. For exam revision only.",
    S("Normal", fontSize=7.5, textColor=colors.HexColor("#555555"), alignment=TA_CENTER, leading=11)
))

doc.build(story, onFirstPage=draw_bg, onLaterPages=draw_bg)
print("Anatomy PDF created:", OUTPUT)

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, PageBreak
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT

import os
os.makedirs("/tmp/workspace/knruhs-physiology", exist_ok=True)

OUTPUT = "/tmp/workspace/knruhs-physiology/KNRUHS_Physiology_CheatSheet.pdf"

doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    rightMargin=1.5*cm, leftMargin=1.5*cm,
    topMargin=1.8*cm, bottomMargin=1.8*cm,
)

DARK      = colors.HexColor("#3a1a5c")
MED       = colors.HexColor("#6a2ea4")
LIGHT_BG  = colors.HexColor("#e8d6f7")
ACCENT    = colors.HexColor("#e06020")
ACC_LIGHT = colors.HexColor("#fff0e0")
RED       = colors.HexColor("#b03030")
GREEN     = colors.HexColor("#1a6e38")
GREY_BG   = colors.HexColor("#f6f4f9")
WHITE     = colors.white

styles = getSampleStyleSheet()
def S(name, **kw):
    base = styles.get(name, styles["Normal"])
    return ParagraphStyle(name+"_c"+str(id(kw)), parent=base, **kw)

cover_title  = S("Title",   fontSize=26, textColor=WHITE,   alignment=TA_CENTER, leading=32)
cover_sub    = S("Normal",  fontSize=13, textColor=ACCENT,  alignment=TA_CENTER, leading=18)
cover_note   = S("Normal",  fontSize=9,  textColor=colors.HexColor("#ddc8f0"), alignment=TA_CENTER)
sec_heading  = S("Heading1",fontSize=11, textColor=WHITE,   alignment=TA_LEFT,  leading=14)
bullet_style = S("Normal",  fontSize=8.2,textColor=colors.HexColor("#222222"), alignment=TA_LEFT, leading=11.5, leftIndent=10)
key_point    = S("Normal",  fontSize=8,  textColor=GREEN,   fontName="Helvetica-Bold", alignment=TA_LEFT, leading=11)
clin_style   = S("Normal",  fontSize=8,  textColor=RED,     fontName="Helvetica-BoldOblique", alignment=TA_LEFT, leading=11)
qr_hdr_s     = S("Normal",  fontSize=8.5,textColor=WHITE,   fontName="Helvetica-Bold")
qr_body_s    = S("Normal",  fontSize=8,  textColor=DARK)

TOPICS = [
    (1,"Cardiac Cycle & Heart Sounds",
     ["Systole: isovolumetric contraction → rapid ejection → reduced ejection",
      "Diastole: isovolumetric relaxation → rapid filling → slow filling → atrial systole",
      "S1 (lub): closure of mitral + tricuspid valves (start of systole)",
      "S2 (dub): closure of aortic + pulmonary valves (end of systole); A2 before P2",
      "S3: rapid ventricular filling (normal in children; pathological in adults = HF); S4: atrial kick (stiff ventricle)"],
     "Wiggers diagram: pressure-volume loops are essential for exam",
     "Clinical: Mitral stenosis → loud S1, opening snap, mid-diastolic murmur; afib common complication"),
    (2,"Blood Pressure Regulation",
     ["Arterial BP = Cardiac Output × Total Peripheral Resistance",
      "Short-term: baroreceptors (carotid sinus, aortic arch), chemoreceptors",
      "Medium-term: RAAS, capillary fluid shift",
      "Long-term: kidneys (pressure natriuresis) – most important",
      "Baroreceptors: high pressure → ↑firing → ↓sympathetic → ↓BP (reflex arc)"],
     "Kidney is the ultimate long-term regulator of BP (Guyton's pressure-natriuresis)",
     "Clinical: Cushing's reflex: raised ICP → hypertension + bradycardia + irregular breathing"),
    (3,"ECG - Normal Waves & Intervals",
     ["P wave: atrial depolarization (0.12 sec); PR interval: 0.12-0.20 sec",
      "QRS complex: ventricular depolarization (< 0.12 sec)",
      "ST segment: early repolarization; T wave: ventricular repolarization",
      "QT interval: total ventricular activity (0.35-0.45 sec); QTc = QT/√RR",
      "Rate: 300/large squares; Axis: normal -30° to +90°"],
     "PR interval prolonged = 1st degree heart block; absent P waves + irregular = AF",
     "Clinical: STEMI → ST elevation; NSTEMI → ST depression; hyperkalaemia → tall peaked T waves"),
    (4,"Respiratory Mechanics & Lung Volumes",
     ["TV (tidal volume): 500 mL; IRV: 3000 mL; ERV: 1100 mL; RV: 1200 mL",
      "VC = IRV + TV + ERV = 4600 mL; TLC = VC + RV = 5800 mL",
      "FRC = ERV + RV = 2300 mL (volume at end of normal expiration)",
      "FEV1/FVC > 80% = normal; < 70% = obstructive (asthma, COPD); VC↓ = restrictive",
      "Compliance = ΔV/ΔP; surfactant ↑compliance; prevents alveolar collapse"],
     "RV cannot be measured by spirometry; use body plethysmography or helium dilution",
     "Clinical: COPD = FEV1/FVC < 0.7; ↑TLC, ↑RV; barrel chest; pursed lip breathing"),
    (5,"Haemoglobin & Oxygen Transport",
     ["O2 transport: 97% bound to Hb; 3% dissolved in plasma",
      "Haemoglobin: 4 globin chains + 4 haem groups; 1 Hb binds 4 O2",
      "P50: PO2 at which Hb is 50% saturated (~26 mmHg)",
      "Right shift (↑P50, ↓affinity): ↑CO2, ↑H+, ↑temp, ↑2,3-DPG (Bohr effect)",
      "Left shift (↓P50, ↑affinity): fetal Hb, CO poisoning, ↓CO2, ↓H+, ↓temp"],
     "Fetal HbF: 2α2γ chains; greater O2 affinity than adult HbA (left shift)",
     "Clinical: CO poisoning → cherry red cyanosis; carboxyHb shifts curve left; treat with 100% O2"),
    (6,"Renal Physiology - GFR & Tubular Function",
     ["GFR: 125 mL/min (180 L/day filtered; 1.5 L urine/day)",
      "Autoregulation: myogenic + tubuloglomerular feedback (macula densa)",
      "PCT: 65% Na, water reabsorption; obligatory reabsorption; glucose, amino acids (all)",
      "Loop of Henle: countercurrent multiplier; thick ascending limb impermeable to water",
      "DCT/collecting duct: aldosterone (Na↑, K↓); ADH (water reabsorption)"],
     "Inulin: gold standard for GFR; creatinine overestimates slightly",
     "Clinical: ATN (acute tubular necrosis) → oliguria, casts in urine, ↑creatinine after ischaemia"),
    (7,"Acid-Base Balance",
     ["pH = 7.35-7.45; PaCO2 = 35-45 mmHg; HCO3- = 22-26 mEq/L",
      "Respiratory acidosis: ↑PaCO2 (hypoventilation); compensation = ↑HCO3- (renal)",
      "Respiratory alkalosis: ↓PaCO2 (hyperventilation); compensation = ↓HCO3-",
      "Metabolic acidosis: ↓HCO3- (AG gap = normal anion gap vs high anion gap causes)",
      "Anion gap = Na - (Cl + HCO3) = 12 ± 2; High AG = MUDPILES"],
     "MUDPILES (high anion gap metabolic acidosis): Methanol, Uraemia, DKA, Propylene glycol, INH, Lactic acidosis, Ethylene glycol, Salicylates",
     "Clinical: DKA → high anion gap metabolic acidosis + respiratory compensation (Kussmaul breathing)"),
    (8,"Neuromuscular Junction",
     ["Motor nerve AP → Ca2+ influx → ACh released from vesicles into synaptic cleft",
      "ACh binds nicotinic receptors on motor end plate → depolarization (EPP)",
      "EPP triggers muscle AP → T-tubules → Ca2+ release from SR (Ryanodine receptor)",
      "Ca2+ binds troponin C → tropomyosin shifts → actin-myosin cross-bridge cycling",
      "ACh degraded by AChE in cleft; choline recycled"],
     "Botulinum toxin: blocks ACh release (SNARE proteins); Tetanus toxin: blocks inhibitory interneurons",
     "Clinical: Myasthenia gravis = autoantibodies against nicotinic ACh receptors → fatigable weakness"),
    (9,"Muscle Contraction - Sliding Filament Theory",
     ["Sarcomere: A band (myosin + actin overlap), I band (actin only), H zone (myosin only), Z disc",
      "During contraction: I band ↓, H zone ↓, A band UNCHANGED",
      "Myosin head binds actin → power stroke (ADP released) → shortening",
      "ATP needed for cross-bridge detachment (rigor mortis = no ATP)",
      "Ca2+ releases troponin-tropomyosin inhibition; actomyosin ATPase cleaves ATP"],
     "A band = constant length (contains full myosin filament)",
     "Clinical: Rigor mortis: ATP depletion post-death → permanent cross-bridges; begins 2-6 hrs, resolves 24-48 hrs"),
    (10,"Endocrinology - Pituitary Hormones",
     ["Anterior pituitary (adenohypophysis): GH, TSH, ACTH, FSH, LH, Prolactin",
      "Posterior pituitary (neurohypophysis): ADH (vasopressin) + Oxytocin (made in hypothalamus, stored here)",
      "GH: insulin-like effect on fat, anti-insulin on carbs; IGF-1 mediates growth effects",
      "Prolactin: inhibited by dopamine; lactation, inhibits GnRH",
      "ADH: acts on V2 receptors in collecting duct → aquaporin 2 insertion → water reabsorption"],
     "Hypothalamus controls anterior pituitary via portal blood; posterior via axons",
     "Clinical: SIADH → ADH↑ → dilutional hyponatraemia; Diabetes insipidus → ADH↓/resistance → polyuria, dilute urine"),
    (11,"Thyroid Hormones",
     ["T3 (active) + T4 (prohormone, deiodinated to T3 in periphery)",
      "Synthesis: Tyrosine + iodide → MIT, DIT → T3, T4 (thyroid peroxidase)",
      "T3/T4 effects: ↑BMR, ↑thermogenesis, ↑HR, ↑GI motility, ↑bone turnover",
      "T3 acts via nuclear receptors → gene transcription",
      "TSH → ↑cAMP → ↑thyroid hormone synthesis; TRH stimulates TSH"],
     "T3 is 3-5x more potent than T4; 80% T3 derived from peripheral T4 conversion",
     "Clinical: Hypothyroidism → ↑TSH, ↓FT4; Hyperthyroidism → ↓TSH, ↑FT4; Graves = TSH-receptor antibodies"),
    (12,"Insulin & Glucagon",
     ["Insulin: β cells; released by glucose↑, amino acids, GLP-1; inhibited by epinephrine, somatostatin",
      "Effects: ↑glucose uptake (GLUT4), ↑glycogenesis, ↑lipogenesis, ↓gluconeogenesis, ↑protein synthesis",
      "Glucagon: α cells; released by fasting, amino acids, epinephrine",
      "Glucagon effects: ↑gluconeogenesis, ↑glycogenolysis, ↑ketogenesis",
      "C-peptide: equimolar to insulin; marker of endogenous insulin production"],
     "GLUT4 in muscle + adipose = insulin-dependent; GLUT2 in liver/pancreas = constitutive",
     "Clinical: Type 1 DM = autoimmune β cell destruction; Type 2 = insulin resistance; C-peptide helps distinguish"),
    (13,"Blood Coagulation",
     ["Extrinsic pathway: Tissue factor + VII → X activation (PT/INR tests this)",
      "Intrinsic pathway: XII → XI → IX → X (aPTT tests this)",
      "Common pathway: X + V → thrombin → fibrin clot",
      "Fibrinolysis: plasminogen → plasmin (tPA) → fibrin degradation products (D-dimer)",
      "Platelet plug: primary haemostasis; fibrin clot: secondary haemostasis"],
     "PT (INR) = extrinsic + common; aPTT = intrinsic + common",
     "Clinical: Haemophilia A = Factor VIII deficiency (↑aPTT, normal PT); Haemophilia B = Factor IX deficiency"),
    (14,"Sensory Physiology - Pain & Special Senses",
     ["Nociceptors: free nerve endings; A-delta (fast, sharp pain) + C fibres (slow, dull/burning)",
      "Gate control theory: large myelinated fibres inhibit pain transmission in dorsal horn",
      "Referred pain: visceral pain felt in dermatome sharing spinal segment",
      "Hearing: sound → tympanic membrane → ossicles → oval window → cochlea → VIII nerve",
      "Vision: rods (scotopic, low light, no colour); cones (photopic, colour, central vision)"],
     "Endorphins, enkephalins = endogenous opioids; act on μ, δ, κ receptors",
     "Clinical: Cardiac pain referred to left arm + jaw (T1-4 dermatomes); renal colic referred to groin (T10-L1)"),
    (15,"Nerve Conduction & Action Potential",
     ["Resting potential: -70 mV (K+ diffusion out + Na+/K+ ATPase)",
      "AP: depolarization (Na+ in, voltage-gated) → repolarization (K+ out) → hyperpolarization",
      "All-or-none law; refractory period (absolute = Na channels inactivated)",
      "Saltatory conduction: myelinated nerves; AP jumps between nodes of Ranvier",
      "Conduction velocity: ↑with myelin, ↑with axon diameter"],
     "Na+/K+ ATPase: 3 Na out, 2 K in; electrogenic pump maintains -70 mV",
     "Clinical: Multiple sclerosis = demyelination → slowed/blocked conduction; VEPs delayed"),
    (16,"Gastrointestinal Physiology",
     ["Gastric acid: parietal cells secrete HCl + intrinsic factor; chief cells secrete pepsinogen",
      "Gastrin (G cells, antrum): ↑acid; Secretin (S cells, duodenum): ↑HCO3-, ↓acid",
      "Pancreatic enzymes: lipase, amylase, proteases (all activated in duodenum by trypsin)",
      "Bile: bile acids (emulsification) + bilirubin; stored in gallbladder; released by CCK",
      "Defecation reflex: rectal distension → parasympathetic → internal sphincter relaxation"],
     "Intrinsic factor + Vit B12 absorbed in terminal ileum; resection → B12 deficiency",
     "Clinical: Zollinger-Ellison syndrome: gastrinoma → high gastrin → peptic ulcers + diarrhoea"),
    (17,"Reproductive Physiology - Menstrual Cycle",
     ["Follicular phase (day 1-14): FSH → follicle growth → oestrogen↑",
      "Ovulation (day 14): LH surge (triggered by oestrogen peak) → ovulation",
      "Luteal phase (day 15-28): LH → corpus luteum → progesterone↑",
      "If fertilization: hCG maintains corpus luteum; hCG = basis of pregnancy test",
      "Progesterone: ↑BBT, thickens cervical mucus, prepares endometrium for implantation"],
     "LH surge = trigger for ovulation; peak oestrogen causes positive feedback on LH",
     "Clinical: PCOS = ↑LH:FSH ratio, ↑androgens, insulin resistance; anovulation → infertility"),
    (18,"Body Fluid Compartments",
     ["TBW = 60% body weight (male); 50% (female)",
      "ICF: 40% BW (2/3 TBW); ECF: 20% BW (1/3 TBW)",
      "ECF = plasma (5% BW) + interstitial (15% BW) + transcellular",
      "ICF: high K+, Mg2+, phosphate; ECF: high Na+, Cl-, HCO3-",
      "Starling forces: hydrostatic pressure pushes out; oncotic (osmotic) pressure pulls in"],
     "Osmolarity = 2×Na + glucose/18 + BUN/2.8; normal = 285-295 mOsm/L",
     "Clinical: Oedema = ↑capillary hydrostatic pressure OR ↓oncotic pressure (hypoalbuminaemia in liver disease)"),
    (19,"Blood - Components & Functions",
     ["RBCs: 4.5-5.5 million/mm³; lifespan 120 days; destroyed in spleen",
      "WBCs: neutrophils (60-70%), lymphocytes (20-30%), monocytes, eosinophils, basophils",
      "Platelets: 1.5-4 lakh/mm³; lifespan 10 days; no nucleus",
      "Plasma proteins: albumin (60%), globulins (36%), fibrinogen (4%)",
      "ESR: ↑in inflammation, pregnancy, anaemia; RBC rouleaux formation"],
     "Erythropoiesis: stem cell → proerythroblast → reticulocyte → RBC; EPO from kidney",
     "Clinical: Anaemia of chronic disease: ↓serum iron, ↓TIBC, ↑ferritin (trapped iron); normocytic"),
    (20,"Higher Functions - Sleep, EEG, Reflexes",
     ["EEG waves: δ (deep sleep/coma), θ (drowsy), α (relaxed/closed eyes), β (alert/thinking)",
      "Sleep stages: NREM (stages 1-4, δ waves in deep sleep) + REM (dreaming, rapid eye movements)",
      "REM sleep: atonia, vivid dreams, ↑HR & BP variability, penile erection",
      "Deep tendon reflexes (DTRs): monosynaptic; spinal levels - biceps C5, triceps C7, knee L4, ankle S1",
      "Babinski reflex: normal in infants (plantar flexion); abnormal in adults = UMN lesion (dorsiflexion)"],
     "REM sleep: first cycle ~90 min after sleep onset; REM duration increases towards morning",
     "Clinical: Narcolepsy = sudden REM sleep; cataplexy (sudden muscle weakness); treat with modafinil"),
]

def draw_bg(canvas, doc):
    w, h = A4
    canvas.setFillColor(DARK)
    canvas.rect(0, h-1.1*cm, w, 1.1*cm, fill=1, stroke=0)
    canvas.setFillColor(DARK)
    canvas.rect(0, 0, w, 0.7*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(w/2, 0.22*cm, "KNRUHS 1st MBBS Physiology Cheat Sheet  |  For Exam Preparation Only")
    canvas.drawRightString(w-1.5*cm, 0.22*cm, f"Page {doc.page}")

story = []

cover_data = [
    [Paragraph("KNRUHS 1st MBBS", cover_title)],
    [Paragraph("PHYSIOLOGY CHEAT SHEET", cover_title)],
    [Paragraph("Top 20 Most Repeated Topics | Exam Quick Reference", cover_sub)],
    [Paragraph("Paper I &amp; Paper II  •  Last 5 Exams Pattern  •  2021–2025", cover_note)],
]
cover_t = Table(cover_data, colWidths=[doc.width])
cover_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK),
    ("TOPPADDING", (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ("LEFTPADDING", (0,0), (-1,-1), 12),
]))
story.append(cover_t)
story.append(Spacer(1, 0.3*cm))

legend_data = [[
    Paragraph("<b>🔑 Key Point</b>", S("Normal", fontSize=8, textColor=GREEN)),
    Paragraph("<b>🏥 Clinical Note</b>", S("Normal", fontSize=8, textColor=RED)),
    Paragraph("<b>★ High Priority Topic</b>", S("Normal", fontSize=8, textColor=DARK)),
]]
legend_t = Table(legend_data, colWidths=[doc.width/3]*3)
legend_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
    ("BOX", (0,0), (-1,-1), 0.5, MED),
    ("TOPPADDING", (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
]))
story.append(legend_t)
story.append(Spacer(1, 0.3*cm))

COL_W = (doc.width - 0.4*cm) / 2

def make_card(num, title, bullets, keypoint, clinical):
    inner = []
    hdr = Table([[Paragraph(f"#{num}  {title}", sec_heading)]], colWidths=[COL_W-0.2*cm])
    hdr.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), MED),
        ("TOPPADDING", (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING", (0,0), (-1,-1), 8),
    ]))
    inner.append(hdr)
    for b in bullets:
        inner.append(Paragraph(f"• {b}", bullet_style))
    inner.append(Spacer(1, 2))
    inner.append(Paragraph(f"🔑 {keypoint}", key_point))
    inner.append(Paragraph(f"🏥 {clinical}", clin_style))
    inner.append(Spacer(1, 4))
    card = Table([[i] for i in inner], colWidths=[COL_W-0.2*cm])
    card.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), GREY_BG),
        ("TOPPADDING", (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
        ("LEFTPADDING", (0,0), (-1,-1), 6),
        ("RIGHTPADDING", (0,0), (-1,-1), 4),
    ]))
    outer = Table([[card]], colWidths=[COL_W])
    outer.setStyle(TableStyle([
        ("BOX", (0,0), (-1,-1), 0.8, MED),
        ("TOPPADDING", (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ]))
    return outer

def build_row(t1, t2=None):
    c1 = make_card(*t1)
    if t2:
        c2 = make_card(*t2)
        row = Table([[c1, Spacer(0.4*cm,1), c2]], colWidths=[COL_W, 0.4*cm, COL_W])
    else:
        row = Table([[c1, Spacer(0.4*cm,1), Spacer(COL_W,1)]], colWidths=[COL_W, 0.4*cm, COL_W])
    row.setStyle(TableStyle([
        ("VALIGN", (0,0), (-1,-1), "TOP"),
        ("TOPPADDING", (0,0), (-1,-1), 0),
        ("BOTTOMPADDING", (0,0), (-1,-1), 0),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ]))
    return row

for i in range(0, len(TOPICS), 2):
    story.append(build_row(TOPICS[i], TOPICS[i+1] if i+1 < len(TOPICS) else None))
    story.append(Spacer(1, 0.25*cm))

story.append(PageBreak())
story.append(Spacer(1, 0.3*cm))
qr_hdr_t = Table([[Paragraph("QUICK REFERENCE: Physiology High-Yield Points", sec_heading)]], colWidths=[doc.width])
qr_hdr_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
]))
story.append(qr_hdr_t)
story.append(Spacer(1, 0.2*cm))

qr_rows = [
    [Paragraph(h, qr_hdr_s) for h in ["Topic", "Normal Value / Key Fact", "Regulatory Mechanism", "Clinical Condition"]],
    ["GFR", "125 mL/min", "Autoregulation (myogenic + TGF)", "ATN: GFR↓, oliguria"],
    ["Resting membrane potential", "-70 mV", "Na+/K+ ATPase + K+ diffusion", "Hyperkalaemia → arrhythmia"],
    ["Cardiac output", "5 L/min (70 mL × 70 bpm)", "Starling's law (preload)", "Heart failure: CO↓"],
    ["PaO2/SpO2", "95-100 mmHg / 97-99%", "Hypoxic pulmonary vasoconstriction", "CO poisoning: SpO2 normal but hypoxic"],
    ["Plasma osmolarity", "285-295 mOsm/L", "ADH (thirst + renal water)", "SIADH: ↓osmolarity, ↓Na+"],
    ["PR interval (ECG)", "0.12-0.20 sec", "AV node delay", "1st degree block: PR > 0.20"],
    ["FEV1/FVC ratio", ">80% normal", "Airway resistance (bronchodilators)", "COPD: < 0.70; Asthma: reversible"],
    ["Cortisol (diurnal)", "Peak 8 AM, nadir midnight", "ACTH from anterior pituitary", "Cushing's: ↑cortisol, ↑glucose, buffalo hump"],
    ["P50 (Hb)", "26 mmHg", "2,3-DPG, pH, temp (Bohr effect)", "CO poisoning: left shift; poor O2 delivery"],
    ["Platelet count", "1.5-4 lakh/mm³", "TPO from liver", "ITP: autoimmune destruction; DIC: consumption"],
]
qr_formatted = []
for i, row in enumerate(qr_rows):
    if i == 0:
        qr_formatted.append(row)
    else:
        qr_formatted.append([Paragraph(str(c), qr_body_s) for c in row])

qr_t = Table(qr_formatted, colWidths=[doc.width*0.18, doc.width*0.22, doc.width*0.3, doc.width*0.3])
qr_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), MED),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, colors.HexColor("#e8d6f7")]),
    ("GRID", (0,0), (-1,-1), 0.3, colors.HexColor("#aaaaaa")),
    ("FONTSIZE", (0,0), (-1,-1), 8),
    ("TOPPADDING", (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
]))
story.append(qr_t)
story.append(Spacer(1, 0.4*cm))

mn_data = [
    [Paragraph("ESSENTIAL PHYSIOLOGY MNEMONICS", S("Normal", fontSize=10, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER))],
    [Paragraph(
        "<b>Lung volumes (can't measure by spirometry):</b> RV, FRC, TLC – need body plethysmography or helium dilution<br/>"
        "<b>O2-Hb curve right shift:</b> CADET (CO2↑, Acid↑, 2,3-DPG↑, Exercise, Temp↑)<br/>"
        "<b>Anterior pituitary hormones:</b> FLAT PiG (FSH, LH, ACTH, TSH, Prolactin, (i)GH)<br/>"
        "<b>Coagulation factors tested:</b> PT/INR = extrinsic (VII) + common; aPTT = intrinsic (VIII,IX,XI,XII) + common<br/>"
        "<b>Blood groups:</b> A=anti-B; B=anti-A; AB=no antibodies (universal recipient); O=both antibodies (universal donor)<br/>"
        "<b>EEG waves memory:</b> Deeper the sleep → slower the wave (β→α→θ→δ)",
        S("Normal", fontSize=8.5, textColor=DARK, leading=14)
    )],
]
mn_t = Table(mn_data, colWidths=[doc.width])
mn_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (0,0), ACCENT),
    ("BACKGROUND", (0,1), (0,1), ACC_LIGHT),
    ("BOX", (0,0), (-1,-1), 1, ACCENT),
    ("TOPPADDING", (0,0), (-1,-1), 7),
    ("BOTTOMPADDING", (0,0), (-1,-1), 7),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
    ("RIGHTPADDING", (0,0), (-1,-1), 10),
]))
story.append(mn_t)
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "★ Covers most frequently tested KNRUHS 1st MBBS Physiology topics. Always reference Guyton & Hall / Ganong. For exam revision only.",
    S("Normal", fontSize=7.5, textColor=colors.HexColor("#555555"), alignment=TA_CENTER, leading=11)
))

doc.build(story, onFirstPage=draw_bg, onLaterPages=draw_bg)
print("Physiology PDF created:", OUTPUT)