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_path = "/tmp/workspace/renal-notes/Renal_Short_Notes_BDS_3rd_Year.pdf"

doc = SimpleDocTemplate(
    output_path,
    pagesize=A4,
    rightMargin=1.8*cm,
    leftMargin=1.8*cm,
    topMargin=1.8*cm,
    bottomMargin=1.8*cm,
    title="Renal Short Notes - BDS 3rd Year",
    author="General Medicine Notes"
)

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle(
    'MainTitle',
    parent=styles['Title'],
    fontSize=16,
    textColor=colors.HexColor('#1a3a6e'),
    spaceAfter=4,
    alignment=TA_CENTER,
    fontName='Helvetica-Bold'
)

subtitle_style = ParagraphStyle(
    'SubTitle',
    parent=styles['Normal'],
    fontSize=9,
    textColor=colors.HexColor('#555555'),
    spaceAfter=8,
    alignment=TA_CENTER,
    fontName='Helvetica'
)

topic_title_style = ParagraphStyle(
    'TopicTitle',
    parent=styles['Heading1'],
    fontSize=13,
    textColor=colors.white,
    spaceBefore=10,
    spaceAfter=6,
    fontName='Helvetica-Bold',
    backColor=colors.HexColor('#1a3a6e'),
    leftIndent=-5,
    rightIndent=-5,
    leading=18
)

subheading_style = ParagraphStyle(
    'SubHeading',
    parent=styles['Heading2'],
    fontSize=10,
    textColor=colors.HexColor('#1a3a6e'),
    spaceBefore=6,
    spaceAfter=2,
    fontName='Helvetica-Bold',
    borderPad=1,
)

body_style = ParagraphStyle(
    'BodyText',
    parent=styles['Normal'],
    fontSize=9,
    textColor=colors.HexColor('#222222'),
    spaceAfter=3,
    leading=13,
    fontName='Helvetica',
    alignment=TA_JUSTIFY
)

bullet_style = ParagraphStyle(
    'Bullet',
    parent=styles['Normal'],
    fontSize=9,
    textColor=colors.HexColor('#222222'),
    spaceAfter=2,
    leading=13,
    fontName='Helvetica',
    leftIndent=14,
    bulletIndent=4,
    bulletFontSize=9
)

def topic_header(title, number):
    return Paragraph(f"  {number}. {title}", topic_title_style)

def subhead(text):
    return Paragraph(text, subheading_style)

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

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

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

elements = []

# ─────── TITLE PAGE ───────
elements.append(Spacer(1, 0.5*cm))
elements.append(Paragraph("SHORT NOTES", title_style))
elements.append(Paragraph("General Medicine | BDS 3rd Year | Gujarat University", subtitle_style))
elements.append(Paragraph("Based on Anil K. Tripathi — General Medicine for BDS", subtitle_style))
elements.append(Paragraph("Topics: Renal System | 7–8 Marks Each", subtitle_style))
elements.append(HRFlowable(width="100%", thickness=2, color=colors.HexColor('#1a3a6e'), spaceAfter=10))
elements.append(Spacer(1, 0.3*cm))

# ─────── 1. NEPHROTIC SYNDROME ───────
elements.append(topic_header("NEPHROTIC SYNDROME", 1))
elements.append(subhead("Definition"))
elements.append(body("A clinical syndrome characterised by massive proteinuria (>3.5 g/day in adults, >40 mg/m²/hr in children), hypoalbuminaemia (<3 g/dL), generalised oedema (anasarca), and hyperlipidaemia with lipiduria."))
elements.append(subhead("Classic Triad / Tetrad"))
elements.append(bullet("Massive proteinuria (>3.5 g/day)"))
elements.append(bullet("Hypoalbuminaemia (<3 g/dL)"))
elements.append(bullet("Generalised oedema (anasarca)"))
elements.append(bullet("Hyperlipidaemia + Lipiduria"))
elements.append(subhead("Causes"))
elements.append(body("<b>Primary (Idiopathic):</b>"))
elements.append(bullet("Minimal Change Disease (MCD) — most common in children"))
elements.append(bullet("Focal Segmental Glomerulosclerosis (FSGS)"))
elements.append(bullet("Membranous Nephropathy — most common in adults"))
elements.append(bullet("Membranoproliferative GN (MPGN)"))
elements.append(body("<b>Secondary:</b>"))
elements.append(bullet("Diabetic nephropathy, SLE (lupus nephritis), Amyloidosis"))
elements.append(bullet("Drugs: NSAIDs, gold, penicillamine, heroin"))
elements.append(bullet("Infections: Hepatitis B/C, HIV, malaria, syphilis"))
elements.append(bullet("Malignancy: Hodgkin's lymphoma (associated with MCD)"))
elements.append(subhead("Pathophysiology"))
elements.append(body("Loss of glomerular polyanion barrier → massive protein leak → hypoalbuminaemia → reduced oncotic pressure → fluid shifts to interstitium → oedema. Liver compensates by overproducing lipoproteins → hyperlipidaemia. Lipiduria occurs when lipoproteins exceed reabsorptive capacity of tubules."))
elements.append(subhead("Clinical Features"))
elements.append(bullet("Puffiness of face (periorbital) especially in mornings — early sign"))
elements.append(bullet("Pitting oedema of lower limbs, ascites, pleural effusion"))
elements.append(bullet("Frothy urine (proteinuria)"))
elements.append(bullet("Pallor, fatigue, anorexia"))
elements.append(bullet("Xanthomas (in hyperlipidaemia)"))
elements.append(subhead("Complications"))
elements.append(bullet("Infections (low IgG) — peritonitis, cellulitis, pneumonia"))
elements.append(bullet("Thromboembolism (loss of antithrombin III) — DVT, renal vein thrombosis"))
elements.append(bullet("Acute Kidney Injury"))
elements.append(bullet("Malnutrition, growth retardation in children"))
elements.append(subhead("Investigations"))
elements.append(bullet("Urine: dipstick 3–4+ protein, 24-hr protein >3.5 g, fatty casts, oval fat bodies"))
elements.append(bullet("Blood: serum albumin <3 g/dL, elevated cholesterol/triglycerides, elevated ESR"))
elements.append(bullet("Renal biopsy — gold standard for type"))
elements.append(subhead("Treatment"))
elements.append(bullet("Treat underlying cause"))
elements.append(bullet("Corticosteroids — Prednisolone 1 mg/kg/day (first line in MCD)"))
elements.append(bullet("Diuretics — Furosemide for oedema; add aldosterone antagonist"))
elements.append(bullet("ACE inhibitors/ARBs — reduce proteinuria"))
elements.append(bullet("Dietary: high protein, low salt, low fat diet"))
elements.append(bullet("Statins for hyperlipidaemia; anticoagulation for thrombosis"))
elements.append(bullet("Cytotoxics (cyclophosphamide) for steroid-resistant cases"))

elements.append(Spacer(1, 0.4*cm))

# ─────── 2. ACUTE AND RAPIDLY PROGRESSIVE GLOMERULONEPHRITIDES ───────
elements.append(topic_header("ACUTE & RAPIDLY PROGRESSIVE GLOMERULONEPHRITIDES", 2))
elements.append(subhead("A. Acute Glomerulonephritis (AGN)"))
elements.append(body("<b>Definition:</b> Sudden onset of haematuria, proteinuria, oedema, hypertension and oliguria due to immune-mediated glomerular inflammation."))
elements.append(body("<b>Prototype:</b> Post-streptococcal GN (PSGN) — most common in children after Group A beta-haemolytic Streptococcal infection (throat/skin)."))
elements.append(body("<b>Latent period:</b> 1–3 weeks after throat infection; 3–6 weeks after skin infection."))
elements.append(body("<b>Pathology:</b> Diffuse proliferative GN; immune complex deposition (IgG + C3) in subepithelial position → 'humps' on EM."))
elements.append(subhead("Clinical Features of AGN"))
elements.append(bullet("Haematuria — smoky/cola-coloured urine (most common)"))
elements.append(bullet("Oedema — periorbital, ankle"))
elements.append(bullet("Hypertension (mild to moderate)"))
elements.append(bullet("Oliguria (↓urine output)"))
elements.append(bullet("Proteinuria (mild, <3.5 g/day — subnephrotic)"))
elements.append(subhead("Investigations"))
elements.append(bullet("Urine: RBC casts, dysmorphic RBCs, proteinuria"))
elements.append(bullet("Blood: ↑ASO titre (PSGN), ↓C3 complement, ↑BUN/creatinine"))
elements.append(bullet("Throat/skin culture: streptococcal organisms"))
elements.append(subhead("Treatment"))
elements.append(bullet("Penicillin to eradicate streptococcus"))
elements.append(bullet("Diuretics + antihypertensives"))
elements.append(bullet("Salt and water restriction"))
elements.append(bullet("Dialysis if severe renal failure — prognosis generally good in children"))
elements.append(Spacer(1, 0.2*cm))
elements.append(subhead("B. Rapidly Progressive Glomerulonephritis (RPGN)"))
elements.append(body("<b>Definition:</b> A syndrome of rapid loss of renal function (50% loss of GFR within weeks to months) with histological finding of crescents in >50% of glomeruli (Crescentic GN)."))
elements.append(body("<b>Types (based on immunofluorescence):</b>"))
elements.append(bullet("Type I — Anti-GBM disease (linear IgG deposits); Goodpasture's syndrome (lung + kidney)"))
elements.append(bullet("Type II — Immune complex mediated (granular deposits); Lupus nephritis, PSGN, IgA nephropathy"))
elements.append(bullet("Type III — Pauci-immune (no/few deposits); ANCA-associated vasculitis (Wegener's GPA, MPA)"))
elements.append(subhead("Clinical Features"))
elements.append(bullet("Haematuria, heavy proteinuria, oliguria/anuria"))
elements.append(bullet("Rapid onset of oedema, hypertension"))
elements.append(bullet("Haemoptysis in Goodpasture's syndrome (pulmonary-renal syndrome)"))
elements.append(bullet("Rapid progression to renal failure within weeks"))
elements.append(subhead("Investigations"))
elements.append(bullet("Urine: RBC casts, heavy proteinuria"))
elements.append(bullet("Anti-GBM antibody (Type I); ANA, anti-dsDNA (Type II); ANCA — c-ANCA/p-ANCA (Type III)"))
elements.append(bullet("Renal biopsy: crescents in >50% glomeruli — diagnostic"))
elements.append(subhead("Treatment"))
elements.append(bullet("High-dose IV methylprednisolone (pulse therapy)"))
elements.append(bullet("Cyclophosphamide (oral/IV)"))
elements.append(bullet("Plasma exchange (plasmapheresis) — especially Type I"))
elements.append(bullet("Dialysis if required"))
elements.append(bullet("Rituximab in ANCA-associated RPGN"))

elements.append(Spacer(1, 0.4*cm))

# ─────── 3. ACUTE KIDNEY INJURY ───────
elements.append(topic_header("ACUTE KIDNEY INJURY (AKI)", 3))
elements.append(subhead("Definition (KDIGO)"))
elements.append(body("Abrupt (within 48 hours) rise in serum creatinine ≥0.3 mg/dL, OR increase in serum creatinine ≥1.5 times baseline within 7 days, OR urine output <0.5 mL/kg/hr for ≥6 hours."))
elements.append(subhead("Classification / Staging (KDIGO)"))

aki_data = [
    ['Stage', 'Serum Creatinine Criteria', 'Urine Output'],
    ['1', '≥0.3 mg/dL rise or 1.5–1.9× baseline', '<0.5 mL/kg/hr for 6–12 h'],
    ['2', '2.0–2.9× baseline', '<0.5 mL/kg/hr for ≥12 h'],
    ['3', '≥3× baseline or ≥4 mg/dL or need for RRT', '<0.3 mL/kg/hr for ≥24 h or anuria ≥12 h'],
]
t = Table(aki_data, colWidths=[1.8*cm, 7*cm, 5.5*cm])
t.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a3a6e')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,-1), 8),
    ('GRID', (0,0), (-1,-1), 0.5, colors.HexColor('#aaaaaa')),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#f0f4ff'), colors.white]),
    ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
    ('PADDING', (0,0), (-1,-1), 4),
]))
elements.append(t)
elements.append(Spacer(1, 0.2*cm))

elements.append(subhead("Causes — Pre-renal, Renal (Intrinsic), Post-renal"))
elements.append(body("<b>Pre-renal (most common, ~60–70%):</b> ↓ renal perfusion"))
elements.append(bullet("Hypovolaemia: dehydration, haemorrhage, burns, diarrhoea"))
elements.append(bullet("↓ Cardiac output: heart failure, cardiogenic shock"))
elements.append(bullet("Vasodilation: sepsis, anaphylaxis, drugs (NSAIDs, ACE inhibitors)"))
elements.append(body("<b>Renal/Intrinsic (~25–35%):</b>"))
elements.append(bullet("Acute Tubular Necrosis (ATN) — most common intrinsic cause; ischaemic or nephrotoxic"))
elements.append(bullet("Nephrotoxins: aminoglycosides, contrast agents, cisplatin, myoglobin (rhabdomyolysis)"))
elements.append(bullet("Glomerulonephritis (AGN, RPGN)"))
elements.append(bullet("Acute Interstitial Nephritis (AIN) — drugs (penicillin, NSAIDs), infections"))
elements.append(bullet("Vascular: renal artery/vein occlusion, HUS, TTP"))
elements.append(body("<b>Post-renal (~5–10%):</b> Obstruction"))
elements.append(bullet("Ureteric: calculi, tumour, retroperitoneal fibrosis"))
elements.append(bullet("Bladder neck/urethral: BPH, stricture, bladder tumour"))
elements.append(subhead("Phases of AKI (ATN)"))
elements.append(bullet("Initiation phase: ↓ GFR, oliguria begins"))
elements.append(bullet("Oliguric phase (1–2 weeks): urine <400 mL/day; ↑ K⁺, ↑ urea, acidosis"))
elements.append(bullet("Diuretic phase: urine output increases, risk of electrolyte loss"))
elements.append(bullet("Recovery phase: GFR normalises over weeks to months"))
elements.append(subhead("Clinical Features"))
elements.append(bullet("Oliguria or anuria, oedema, hypertension"))
elements.append(bullet("Uraemia: nausea, vomiting, anorexia, altered sensorium, uraemic frost"))
elements.append(bullet("Hyperkalaemia: muscle weakness, cardiac arrhythmias"))
elements.append(bullet("Metabolic acidosis: Kussmaul breathing"))
elements.append(bullet("Pulmonary oedema, pericarditis (in severe AKI)"))
elements.append(subhead("Investigations"))
elements.append(bullet("Urine: osmolality, sodium, specific gravity (to differentiate pre-renal vs. ATN)"))
elements.append(bullet("Blood: ↑ serum creatinine, ↑ BUN, ↑ K⁺, ↓ HCO₃⁻, ↑ phosphate, ↓ Ca²⁺"))
elements.append(bullet("FENa <1% = pre-renal; >1% = intrinsic renal (ATN)"))
elements.append(bullet("Renal USG: size, obstruction; biopsy if intrinsic cause unclear"))
elements.append(subhead("Treatment"))
elements.append(bullet("Identify and remove the cause (stop nephrotoxins)"))
elements.append(bullet("Fluid resuscitation for pre-renal; avoid fluid overload in ATN"))
elements.append(bullet("Hyperkalaemia: calcium gluconate, insulin-dextrose, sodium bicarbonate, Kayexalate, dialysis"))
elements.append(bullet("Treat metabolic acidosis, pulmonary oedema, hypertension"))
elements.append(bullet("Nutritional support: adequate calories, restrict K⁺ and phosphate"))
elements.append(bullet("Dialysis: if conservative measures fail (see RRT indications)"))

elements.append(Spacer(1, 0.4*cm))

# ─────── 4. CHRONIC KIDNEY DISEASE ───────
elements.append(topic_header("CHRONIC KIDNEY DISEASE (CKD)", 4))
elements.append(subhead("Definition (KDIGO)"))
elements.append(body("Abnormalities of kidney structure or function, present for >3 months, with implications for health. Defined by GFR <60 mL/min/1.73 m² and/or markers of kidney damage (albuminuria, haematuria, structural abnormality) persisting >3 months."))
elements.append(subhead("Staging of CKD"))

ckd_data = [
    ['Stage', 'Description', 'GFR (mL/min/1.73 m²)'],
    ['G1', 'Normal or high (with markers)', '≥90'],
    ['G2', 'Mildly decreased', '60–89'],
    ['G3a', 'Mildly–moderately decreased', '45–59'],
    ['G3b', 'Moderately–severely decreased', '30–44'],
    ['G4', 'Severely decreased', '15–29'],
    ['G5', 'Kidney failure (ESKD)', '<15 or on dialysis'],
]
t2 = Table(ckd_data, colWidths=[2*cm, 7*cm, 5.3*cm])
t2.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a3a6e')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,-1), 8),
    ('GRID', (0,0), (-1,-1), 0.5, colors.HexColor('#aaaaaa')),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#f0f4ff'), colors.white]),
    ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
    ('PADDING', (0,0), (-1,-1), 4),
]))
elements.append(t2)
elements.append(Spacer(1, 0.2*cm))

elements.append(subhead("Causes"))
elements.append(bullet("Diabetic nephropathy — #1 cause worldwide"))
elements.append(bullet("Hypertensive nephrosclerosis — #2 cause"))
elements.append(bullet("Chronic glomerulonephritis (IgA nephropathy, FSGS, MPGN)"))
elements.append(bullet("Chronic pyelonephritis / reflux nephropathy"))
elements.append(bullet("Polycystic kidney disease (PKD — autosomal dominant)"))
elements.append(bullet("Obstructive uropathy, analgesic nephropathy, SLE"))
elements.append(subhead("Pathophysiology"))
elements.append(body("Progressive nephron loss → hyperfiltration in remaining nephrons → proteinuria → tubulointerstitial damage → fibrosis → progressive GFR decline. The final common pathway is glomerulosclerosis and interstitial fibrosis."))
elements.append(subhead("Clinical Features / Complications (Uraemic Syndrome)"))
elements.append(body("<b>Fluid and Electrolytes:</b> Fluid retention, hypertension, oedema, hyperkalaemia, metabolic acidosis, hyperphosphataemia, hypocalcaemia"))
elements.append(body("<b>Cardiovascular:</b> Hypertension (most common), LVH, heart failure, accelerated atherosclerosis, pericarditis, uraemic pericarditis"))
elements.append(body("<b>Haematological:</b> Normocytic normochromic anaemia (↓ erythropoietin), bleeding tendency (platelet dysfunction)"))
elements.append(body("<b>Skeletal:</b> Renal osteodystrophy — osteitis fibrosa cystica (↑ PTH), osteomalacia, adynamic bone disease"))
elements.append(body("<b>Neurological:</b> Peripheral neuropathy, encephalopathy, restless leg syndrome"))
elements.append(body("<b>GI:</b> Nausea, vomiting, anorexia, uraemic fetor, peptic ulcers, GI bleeding"))
elements.append(body("<b>Skin:</b> Uraemic pruritus, uraemic frost, pallor, hyperpigmentation"))
elements.append(subhead("Investigations"))
elements.append(bullet("Serum creatinine, BUN, eGFR, electrolytes"))
elements.append(bullet("Urine: ACR (albumin-to-creatinine ratio), microscopy"))
elements.append(bullet("Haemoglobin, ferritin, PTH, phosphate, calcium, vitamin D levels"))
elements.append(bullet("Renal USG: small echogenic kidneys (bilateral) — hallmark of CKD"))
elements.append(bullet("Renal biopsy if cause unclear"))
elements.append(subhead("Treatment"))
elements.append(body("<b>Specific:</b>"))
elements.append(bullet("Control blood sugar (target HbA1c <7%), blood pressure (<130/80 mmHg)"))
elements.append(bullet("ACE inhibitors/ARBs — first-line to reduce proteinuria and slow progression"))
elements.append(bullet("SGLT2 inhibitors (empagliflozin, dapagliflozin) — slow CKD progression"))
elements.append(body("<b>Symptomatic / Complications:</b>"))
elements.append(bullet("Anaemia: Erythropoiesis-stimulating agents (ESA) + IV iron"))
elements.append(bullet("Hyperphosphataemia: Phosphate binders (calcium carbonate, sevelamer)"))
elements.append(bullet("Secondary hyperparathyroidism: Active Vitamin D (calcitriol)"))
elements.append(bullet("Metabolic acidosis: sodium bicarbonate"))
elements.append(bullet("Diet: low protein (0.6–0.8 g/kg/day), low K⁺, low phosphate, salt restriction"))
elements.append(bullet("Avoid nephrotoxins: NSAIDs, contrast dye, aminoglycosides"))
elements.append(bullet("Prepare for RRT when GFR approaching 10–15 mL/min"))

elements.append(Spacer(1, 0.4*cm))

# ─────── 5. RENAL REPLACEMENT THERAPY ───────
elements.append(topic_header("RENAL REPLACEMENT THERAPY (RRT)", 5))
elements.append(subhead("Definition"))
elements.append(body("All therapies that replace the excretory function of failed kidneys, including haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation."))
elements.append(subhead("Indications for Initiation of Dialysis — 'AEIOU'"))
elements.append(bullet("A — Acidosis: Metabolic acidosis refractory to bicarbonate (pH <7.1)"))
elements.append(bullet("E — Electrolyte imbalance: Hyperkalaemia (K⁺ >6.5 mEq/L) unresponsive to treatment"))
elements.append(bullet("I — Intoxication: Drug/toxin overdose (lithium, salicylates, methanol, ethylene glycol)"))
elements.append(bullet("O — Overload: Fluid overload/pulmonary oedema unresponsive to diuretics"))
elements.append(bullet("U — Uraemia: Uraemic symptoms (encephalopathy, pericarditis, uraemic bleeding, nausea)"))
elements.append(bullet("GFR <10 mL/min (or <15 in diabetics) even without symptoms"))

elements.append(subhead("A. Haemodialysis (HD)"))
elements.append(body("Blood is pumped through an extracorporeal circuit across a semipermeable membrane (dialyser). Waste products and excess water are removed by diffusion and ultrafiltration."))
elements.append(body("<b>Access:</b> Arteriovenous fistula (AVF) — preferred; temporary: tunnelled catheter (IJV)."))
elements.append(body("<b>Schedule:</b> Usually 3 sessions/week, 3–4 hours per session."))
elements.append(body("<b>Advantages:</b> Efficient, supervised, suited for acute situations."))
elements.append(body("<b>Disadvantages:</b> Requires vascular access, anticoagulation, cardiovascular stress, infection risk."))
elements.append(body("<b>Complications:</b> Hypotension (most common during HD), muscle cramps, air embolism, dialysis disequilibrium syndrome, AVF thrombosis, infection, amyloidosis (β2-microglobulin)."))

elements.append(subhead("B. Peritoneal Dialysis (PD)"))
elements.append(body("Dialysis fluid (dialysate) is instilled into the peritoneal cavity via a Tenckhoff catheter. The peritoneal membrane acts as the dialyser. Waste diffuses into dialysate which is then drained."))
elements.append(body("<b>Types:</b>"))
elements.append(bullet("CAPD (Continuous Ambulatory PD): 4 exchanges/day manually; continuous"))
elements.append(bullet("APD (Automated PD): machine performs exchanges overnight"))
elements.append(body("<b>Advantages:</b> Home-based, gentle continuous therapy, preserves residual renal function, better for cardiovascular stability."))
elements.append(body("<b>Disadvantages:</b> Peritonitis risk, protein loss, technique failure."))
elements.append(body("<b>Complications:</b> Peritonitis (#1 complication — S. epidermidis most common), catheter block/leak, hernia, hyperglycaemia, weight gain."))

elements.append(subhead("C. Continuous Renal Replacement Therapy (CRRT)"))
elements.append(body("Used in critically ill (ICU) patients with haemodynamic instability. Provides continuous, slow, gentle fluid and solute removal. Types: CVVH, CVVHD, CVVHDF."))

elements.append(subhead("Adequacy of Dialysis"))
elements.append(bullet("Kt/V ≥1.2 per session (HD) and ≥1.7 per week (PD)"))
elements.append(bullet("Urea Reduction Ratio (URR) ≥65%"))

elements.append(Spacer(1, 0.4*cm))

# ─────── 6. KIDNEY FAILURE ───────
elements.append(topic_header("KIDNEY FAILURE (End-Stage Kidney Disease — ESKD)", 6))
elements.append(subhead("Definition"))
elements.append(body("Irreversible loss of kidney function requiring renal replacement therapy (dialysis or transplantation) for survival. Also termed End-Stage Renal Disease (ESRD). GFR <15 mL/min/1.73 m² (Stage G5 CKD)."))
elements.append(subhead("Aetiology"))
elements.append(bullet("Diabetic nephropathy (~40% — leading cause globally)"))
elements.append(bullet("Hypertensive nephrosclerosis (~25%)"))
elements.append(bullet("Chronic glomerulonephritis (~15%)"))
elements.append(bullet("Polycystic kidney disease, chronic pyelonephritis, obstructive uropathy"))
elements.append(subhead("Clinical Features (Uraemic Syndrome)"))
elements.append(body("Uraemic syndrome reflects accumulation of nitrogenous waste products:"))
elements.append(bullet("General: fatigue, anorexia, weight loss, pruritus"))
elements.append(bullet("CVS: hypertension, pericarditis (uraemic), heart failure, arrhythmias"))
elements.append(bullet("CNS: encephalopathy, asterixis ('flapping tremor'), seizures, coma"))
elements.append(bullet("Haematology: normochromic normocytic anaemia, bleeding tendency"))
elements.append(bullet("GI: nausea, vomiting, uraemic fetor (fishy/ammoniacal breath), GI bleeding"))
elements.append(bullet("Musculoskeletal: renal osteodystrophy, myopathy, fractures"))
elements.append(bullet("Respiratory: Kussmaul breathing (acidosis), uraemic lung (pulmonary oedema)"))
elements.append(bullet("Skin: uraemic frost (urea crystals on skin), sallow pigmentation, pruritus"))
elements.append(subhead("Investigations"))
elements.append(bullet("Serum creatinine markedly ↑ (often >8–10 mg/dL), BUN ↑, eGFR <15"))
elements.append(bullet("Hyperkalaemia, metabolic acidosis (low HCO₃⁻), ↑ phosphate, ↓ calcium"))
elements.append(bullet("Anaemia (Hb <10 g/dL), ↑ PTH"))
elements.append(bullet("USG: bilaterally small, echogenic kidneys (except PKD, amyloid, diabetic — may be normal/large)"))
elements.append(subhead("Management"))
elements.append(body("<b>Conservative management:</b> Low protein diet, salt restriction, manage BP, anaemia, bone disease, cardiovascular risk."))
elements.append(body("<b>Renal Replacement Therapy:</b>"))
elements.append(bullet("Haemodialysis — most common"))
elements.append(bullet("Peritoneal dialysis — home-based"))
elements.append(bullet("Renal transplantation — best long-term outcome"))
elements.append(subhead("Prognosis"))
elements.append(body("Without RRT, ESKD is fatal. 5-year survival on dialysis ~35–40%. Transplanted patients have significantly better survival and quality of life. Major cause of death: Cardiovascular disease."))

elements.append(Spacer(1, 0.4*cm))

# ─────── 7. INDICATIONS FOR LIVER AND KIDNEY TRANSPLANT ───────
elements.append(topic_header("INDICATIONS FOR LIVER AND KIDNEY TRANSPLANTATION", 7))
elements.append(subhead("A. Kidney Transplantation"))
elements.append(body("<b>Indication: End-Stage Renal Disease (ESKD) / GFR <15 mL/min — any chronic, irreversible kidney disease requiring dialysis or with GFR about to reach this threshold.</b>"))
elements.append(body("<b>Common Primary Diagnoses:</b>"))
elements.append(bullet("Diabetic nephropathy (most common indication, ~40%)"))
elements.append(bullet("Hypertensive nephrosclerosis (~25%)"))
elements.append(bullet("Chronic glomerulonephritis (IgA nephropathy, FSGS, MPGN)"))
elements.append(bullet("Polycystic kidney disease (ADPKD)"))
elements.append(bullet("Lupus nephritis (SLE)"))
elements.append(bullet("Chronic pyelonephritis / reflux nephropathy"))
elements.append(bullet("Alport syndrome, oxalosis, cystinosis"))
elements.append(body("<b>Preemptive transplantation</b> (before dialysis) is preferred when GFR 10–15 mL/min — offers best outcomes."))
elements.append(subhead("Contraindications to Kidney Transplant"))
elements.append(body("<b>Absolute:</b> Active malignancy, active systemic infection, active/untreated psychiatric illness, irreversible extra-renal disease limiting survival, ABO incompatibility (without desensitisation)."))
elements.append(body("<b>Relative:</b> Severe obesity (BMI >40), advanced age, significant cardiovascular disease (must be optimised), active substance abuse, HIV (now treatable), non-compliance."))

elements.append(Spacer(1, 0.3*cm))
elements.append(subhead("B. Liver Transplantation"))
elements.append(body("<b>General Principle: Any form of irreversible acute or chronic liver disease with poor prognosis is a potential indication.</b>"))
elements.append(body("<b>MELD Score</b> (Model for End-stage Liver Disease) is used to prioritise candidates. MELD ≥15 — benefits exceed risks of transplantation."))
elements.append(body("<b>Chronic Liver Disease (most common indications):</b>"))
elements.append(bullet("Chronic Hepatitis C (HCV) cirrhosis — historically most common (now declining with DAA therapy)"))
elements.append(bullet("Alcoholic liver disease (ALD) / alcohol-associated cirrhosis"))
elements.append(bullet("Non-alcoholic steatohepatitis (NASH) cirrhosis — rapidly increasing"))
elements.append(bullet("Chronic Hepatitis B (HBV) cirrhosis"))
elements.append(bullet("Primary Biliary Cholangitis (PBC)"))
elements.append(bullet("Primary Sclerosing Cholangitis (PSC) — also associated with IBD"))
elements.append(bullet("Autoimmune hepatitis"))
elements.append(bullet("Wilson's disease, haemochromatosis, alpha-1 antitrypsin deficiency"))
elements.append(bullet("Biliary atresia — most common indication in children"))
elements.append(body("<b>Acute Liver Failure (Fulminant Hepatic Failure):</b>"))
elements.append(bullet("Viral hepatitis A, B"))
elements.append(bullet("Drug-induced liver failure (paracetamol/acetaminophen — most common drug cause)"))
elements.append(bullet("Autoimmune hepatitis"))
elements.append(bullet("Wilson's disease (acute presentation)"))
elements.append(bullet("Amanita poisoning (mushroom)"))
elements.append(body("<b>Malignancy:</b>"))
elements.append(bullet("Hepatocellular carcinoma (HCC) within Milan criteria (single lesion ≤5 cm OR ≤3 lesions each ≤3 cm, no vascular invasion, no metastasis)"))
elements.append(bullet("Cholangiocarcinoma (hilar) — selected cases with neoadjuvant chemoradiation"))
elements.append(bullet("Neuroendocrine tumour liver metastasis (selected)"))
elements.append(body("<b>Metabolic/Other:</b>"))
elements.append(bullet("Familial amyloidotic polyneuropathy (transthyretin amyloidosis)"))
elements.append(bullet("Hyperoxaluria type 1"))
elements.append(bullet("Crigler-Najjar syndrome type I"))
elements.append(subhead("Contraindications to Liver Transplant"))
elements.append(body("<b>Absolute:</b> Extrahepatic malignancy (metastatic), active uncontrolled infection/sepsis, severe cardiopulmonary disease, active alcohol/drug abuse (typically requires ≥6 months abstinence), cholangiocarcinoma beyond special protocols."))
elements.append(body("<b>Relative:</b> Portal vein thrombosis, HIV, age >70, severe obesity, prior abdominal surgeries, HCC beyond Milan criteria."))

elements.append(Spacer(1, 0.3*cm))
elements.append(subhead("Combined Liver-Kidney Transplant (SLKT)"))
elements.append(body("Indicated when both organs are irreversibly failed — e.g., hepatic failure with CKD (GFR <30), primary hyperoxaluria type 1, polycystic disease with both liver and kidney involvement."))

elements.append(Spacer(1, 0.5*cm))
elements.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a3a6e'), spaceAfter=6))
elements.append(Paragraph("Prepared for BDS 3rd Year | Gujarat University | General Medicine", subtitle_style))
elements.append(Paragraph("Reference: Anil K. Tripathi — General Medicine for BDS | Brenner & Rector's The Kidney | Goldman-Cecil Medicine", subtitle_style))

# Build PDF
doc.build(elements)
print(f"PDF created: {output_path}")