from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.lib.units import cm
from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, PageBreak, KeepTogether
from reportlab.pdfbase.ttfonts import TTFont
from reportlab.pdfbase import pdfmetrics
from reportlab.lib.colors import HexColor

OUT = '/tmp/workspace/aki-harrison22/output/Acute_Kidney_Injury_Harrison_22e_6_Page_Note.pdf'

styles = getSampleStyleSheet()
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styles.add(ParagraphStyle(name='SubTitle', parent=styles['Normal'], fontName='Helvetica', fontSize=10.3, leading=14, textColor=HexColor('#425466'), alignment=TA_CENTER, spaceAfter=12))
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styles.add(ParagraphStyle(name='Small', parent=styles['BodyText'], fontName='Helvetica', fontSize=8.25, leading=10.5, textColor=HexColor('#405266'), spaceAfter=4))
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styles.add(ParagraphStyle(name='TableText', parent=styles['BodyText'], fontName='Helvetica', fontSize=8.15, leading=10.1))
styles.add(ParagraphStyle(name='TableHead', parent=styles['BodyText'], fontName='Helvetica-Bold', fontSize=8.3, leading=10.1, textColor=colors.white))

P = lambda text, sty='Bodyx': Paragraph(text, styles[sty])

def bullet(items):
    return [P('• ' + x) for x in items]

def tbl(data, widths, header=True):
    conv=[]
    for r,row in enumerate(data):
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    if header:
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        if r%2==0: ts.append(('BACKGROUND',(0,r),(-1,r),HexColor('#EEF5F8')))
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def info_box(text):
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def footer(canvas, doc):
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    canvas.drawString(1.55*cm,0.77*cm,'Acute Kidney Injury | Harrison\'s Principles of Internal Medicine, 22e')
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doc=SimpleDocTemplate(OUT, pagesize=A4, rightMargin=1.55*cm,leftMargin=1.55*cm,topMargin=1.35*cm,bottomMargin=1.55*cm)
story=[]

# Page 1
story += [P('Acute Kidney Injury', 'Title2'), P('Six-page examination note based on <b>Harrison\'s Principles of Internal Medicine, 22nd edition (2025)</b>, Chapter 321', 'SubTitle'),
          P('1. Definition, staging, and significance','H1x'),
          P('<b>Acute kidney injury (AKI)</b>, formerly called acute renal failure, is impairment of renal filtration and excretory function that develops over days to weeks, usually known or expected to have occurred within 7 days. It leads to retention of nitrogenous and other waste products, often with reduced urine output. AKI is a clinical syndrome: functional impairment can occur with or without demonstrable structural parenchymal damage.','Bodyx'),
          info_box('<b>KDIGO diagnostic definition:</b> an increase in serum creatinine (SCr) by <b>at least 0.3 mg/dL</b> within 48 hours, or SCr <b>at least 1.5 times baseline</b> within 7 days, or urine output <b>0.5 mL/kg/hour for more than 6 hours</b>.'),
          P('Severity staging (KDIGO)','H2x'),
          tbl([['Stage','Serum creatinine','Urine output'],['1','1.5-1.9 times baseline OR increase ≥0.3 mg/dL (≥26.5 μmol/L)','<0.5 mL/kg/h for 6-12 h'],['2','2.0-2.9 times baseline','<0.5 mL/kg/h for ≥12 h'],['3','≥3 times baseline OR SCr ≥4.0 mg/dL (≥353.6 μmol/L) OR renal replacement therapy','<0.3 mL/kg/h for ≥24 h OR anuria ≥12 h']], [2.0*cm,8.3*cm,6.9*cm]),
          P('Epidemiology and clinical importance','H2x')] + bullet(['AKI complicates approximately 5-7% of acute-care hospital admissions and up to 30% of ICU admissions.', 'Risk is amplified by older age, pre-existing chronic kidney disease (CKD), diabetes, reduced renal reserve, sepsis, shock, exposure to nephrotoxins, major surgery, heart failure, and liver failure.', 'AKI is associated with mortality during acute illness and with subsequent CKD progression and cardiovascular risk, even in survivors.']) + [
          P('<b>Exam focus:</b> Do not equate AKI with oliguria. Creatinine may rise late, and substantial AKI can be non-oliguric. Interpret SCr in the context of baseline function, timing, fluid balance, and muscle mass.','Small'), PageBreak()]

# Page 2
story += [P('2. Etiology and pathophysiology','H1x'), P('Harrison groups AKI into <b>prerenal azotemia</b>, <b>intrinsic renal parenchymal disease</b>, and <b>postrenal obstruction</b>. This classification provides the framework for initial evaluation and urgent treatment.','Bodyx'),
          tbl([['Category','Mechanism','Illustrative causes'],['Prerenal','Reduced renal plasma flow and glomerular hydrostatic pressure, initially without parenchymal injury.','True volume depletion: hemorrhage, vomiting, diarrhea, burns. Reduced effective arterial volume: heart failure, cirrhosis, sepsis. Drugs impairing autoregulation: NSAIDs, ACE inhibitors/ARBs in susceptible states.'],['Intrinsic renal','Direct injury to tubules, interstitium, glomeruli, or renal vessels.','Acute tubular necrosis (ATN), acute interstitial nephritis, glomerulonephritis, vasculitis, thrombotic microangiopathy, pigment nephropathy, vascular injury.'],['Postrenal','Obstruction of urinary drainage causing increased tubular pressure and reduced GFR.','Prostatic enlargement, stones, pelvic/retroperitoneal malignancy, neurogenic bladder, urethral or catheter obstruction.']], [2.3*cm,6.3*cm,8.6*cm]),
          P('Prerenal azotemia','H2x'), P('The commonest form of AKI. Renal hypoperfusion activates compensatory sodium and water retention. By definition, there is no initial renal parenchymal damage and function should recover promptly after restoration of perfusion and intraglomerular hemodynamics. Persistent hypoperfusion can cause ischemic tubular injury and ATN.','Bodyx'),
          P('Intrinsic AKI: acute tubular necrosis','H2x'), P('ATN is the most common intrinsic cause. It commonly follows prolonged ischemia, sepsis, or exposure to nephrotoxins. Tubular epithelial injury, inflammation, altered microcirculation, tubular obstruction by casts, and back-leak of filtrate contribute to the fall in GFR.','Bodyx'),
          P('Important intrinsic patterns','H2x'),
          tbl([['Disorder','Typical clue'],['ATN','Ischemic or toxic exposure; muddy brown granular casts and tubular epithelial cells/casts.'],['Acute interstitial nephritis','Drug exposure or infection; pyuria, white-cell casts, sometimes rash, fever, eosinophilia.'],['Glomerulonephritis / vasculitis','Hematuria, dysmorphic red cells or RBC casts, proteinuria, hypertension, systemic features.'],['Rhabdomyolysis','Muscle injury, high creatine kinase, dipstick positive for blood with few/no RBCs; pigment tubular injury.']], [5.0*cm,12.2*cm]),
          P('<b>Postrenal AKI:</b> obstruction must be actively excluded, especially in older men, anuria, fluctuating urine volume, pelvic malignancy, stone disease, or neurogenic bladder. Early relief may lead to substantial recovery.','Small'), PageBreak()]

# Page 3
story += [P('3. Clinical assessment and diagnosis','H1x'), P('The immediate goals are to confirm AKI, determine severity and urgency, identify the cause, and detect complications that require urgent therapy. A focused clinical assessment is more useful than isolated laboratory values.','Bodyx'),
          P('History','H2x')] + bullet(['Baseline SCr, previous urinalysis, CKD, diabetes, hypertension, heart/liver disease, and recent hospitalizations.', 'Fluid loss or poor intake: diarrhea, vomiting, hemorrhage, fever, burns, diuretics. Symptoms of sepsis or shock.', 'Medication review: NSAIDs, ACE inhibitors/ARBs, diuretics, aminoglycosides, antimicrobials, chemotherapy, immune checkpoint inhibitors, lithium, and iodinated contrast.', 'Symptoms of obstruction: weak stream, hesitancy, incomplete emptying, colic, anuria. Ask about malignancy and prostate disease.', 'Systemic clues: rash, arthralgia, sinus/pulmonary symptoms, hemoptysis, edema, muscle pain, dark urine.']) + [
          P('Examination','H2x')] + bullet(['Vital signs and perfusion: hypotension, fever, tachycardia, mean arterial pressure.', 'Volume status: mucous membranes, jugular venous pressure, orthostatic change, edema, lung crackles, ascites, and daily weight.', 'Bladder distension; prostate/pelvic or systemic findings where appropriate; signs of infection, vasculitis, or embolic disease.']) + [
          P('Initial tests','H2x'),
          tbl([['Test','Purpose / useful findings'],['Serial SCr, urea, electrolytes, bicarbonate','Confirm trajectory; detect hyperkalemia, acidosis, and azotemia.'],['Urinalysis and urine sediment','Protein, blood, cells, casts, crystals. Sediment may identify ATN, glomerular disease, or interstitial nephritis.'],['Urine volume and fluid chart','Identifies oliguria/anuria; guides resuscitation and assessment of response.'],['Urine sodium indices','FENa or FEUrea can support a prerenal versus tubular process, but are not definitive and are affected by diuretics, CKD, sepsis, and mixed disease.'],['Renal ultrasound','Assesses kidney size and hydronephrosis; evaluates possible obstruction.'],['Targeted blood tests','CBC, creatine kinase, LDH, complements, serology, cultures, hemolysis tests, or drug levels when indicated.']], [5.3*cm,11.9*cm]),
          info_box('<b>Urgent red flags:</b> anuria, refractory hyperkalemia, pulmonary edema/hypoxemia, severe acidemia, uremic encephalopathy or pericarditis, suspected rapidly progressive glomerulonephritis, thrombotic microangiopathy, or obstructed infected urinary system.'), PageBreak()]

# Page 4
story += [P('4. Prevention and general management','H1x'), P('Management is directed to the cause, while maintaining perfusion and preventing further renal insult. Care must be individualized to the patient\'s hemodynamic state and comorbid disease.','Bodyx'),
          P('Core measures from Harrison','H2x'),
          tbl([['Priority','Practical action'],['Optimize hemodynamics','Volume resuscitation when hypovolemia is present; use vasopressors judiciously when needed. Harrison lists a target mean arterial pressure >65 mmHg as a general goal. Avoid both ongoing hypoperfusion and indiscriminate fluid overload.'],['Remove nephrotoxins','Stop, substitute, or minimize ACE inhibitors, ARBs, NSAIDs, aminoglycosides, selected antibiotics, chemotherapeutic agents, checkpoint inhibitors, and other potential nephrotoxins where clinically feasible.'],['Treat the precipitating illness','Prompt source control and antimicrobials in sepsis; correction of hemorrhage or cardiac dysfunction; relief of obstruction; disease-specific treatment for glomerular, vascular, interstitial, pigment, or crystal-associated injury.'],['Medication stewardship','Dose and interval-adjust drugs to current renal function. SCr can overestimate renal function in non-steady-state AKI.'],['Monitoring','Close observation of fluid intake/output, daily weight, SCr, potassium, bicarbonate, phosphate, calcium, and clinical evidence of volume overload.'],['Nutrition','Avoid negative nitrogen balance. Harrison advises adequate protein/calorie intake, approximately 20-30 kcal/kg/day, preferably enterally when oral intake is not possible.']], [4.2*cm,13.0*cm]),
          P('Fluid management','H2x'), P('Fluid therapy is appropriate for true volume depletion or impaired effective circulating volume, but fluid overload independently worsens outcomes. Reassess frequently using clinical examination, urine output, hemodynamics, and where available, bedside ultrasound or invasive monitoring in complex shock states. In heart failure and cirrhosis, total body fluid excess may coexist with low effective arterial volume.','Bodyx'),
          P('Prevention in high-risk patients','H2x')] + bullet(['Recognize susceptibility before major surgery, contrast studies, sepsis, or exposure to nephrotoxic combinations.', 'Optimize intravascular volume and perfusion; avoid sustained hypotension.', 'Use the lowest necessary nephrotoxic exposure and review interacting medications.', 'Monitor creatinine and urine output after a high-risk event.']) + [
          info_box('<b>Not recommended as renoprotective therapy:</b> Harrison notes that low-dose dopamine, fenoldopam, and vasopressin have not been shown to protect kidneys from acute injury in critical illness.'), PageBreak()]

# Page 5
story += [P('5. Treatment of complications and renal replacement therapy','H1x'), P('Complications determine immediate risk. Treat life-threatening abnormalities while pursuing correction of the underlying AKI.','Bodyx'),
          tbl([['Complication','Management principles in Harrison'],['Volume overload','Restrict salt and water. Consider diuretics when responsive; use ultrafiltration or renal replacement therapy (RRT) for refractory overload, particularly pulmonary edema.'],['Hyperkalemia','Restrict potassium intake; stop potassium-sparing drugs and contributors such as ACE inhibitors/ARBs/NSAIDs where possible. Promote urinary loss with loop diuretics if appropriate. Temporize with insulin plus glucose and inhaled beta-agonist. Give calcium gluconate or calcium chloride (1 g) for ECG changes or cardiotoxicity. Potassium binders may be used in selected cases.'],['Metabolic acidosis','Sodium bicarbonate can be considered when severe, with Harrison listing pH <7.2 and a goal serum bicarbonate >15 mmol/L. RRT for refractory or severe acidemia.'],['Hyperphosphatemia','Dietary phosphate restriction and phosphate binders with meals where indicated.'],['Hypocalcemia','Calcium therapy if symptomatic.'],['Hypermagnesemia','Stop magnesium-containing antacids/laxatives; manage severe cases with RRT if needed.'],['Drug accumulation','Reassess all drug doses and frequencies, including antimicrobials, analgesics, antidiabetic drugs, and anticoagulants.']], [4.35*cm,12.85*cm]),
          P('Indications for renal replacement therapy','H2x'), P('RRT should be initiated for standard, definitive indications rather than solely for a particular SCr value. A useful mnemonic is <b>AEIOU</b>:','Bodyx'),
          tbl([['A','Acidosis','Severe or progressive metabolic acidemia refractory to medical treatment.'],['E','Electrolytes','Refractory, dangerous hyperkalemia or other severe electrolyte disturbance.'],['I','Intoxications','Dialyzable poison or drug exposure in the appropriate clinical setting.'],['O','Overload','Refractory fluid overload, especially pulmonary edema/hypoxemia.'],['U','Uremia','Uremic encephalopathy, pericarditis, bleeding, severe nausea/vomiting, or other major manifestations.']], [1.1*cm,3.0*cm,13.1*cm], header=False),
          P('Choice of modality','H2x'), P('Intermittent hemodialysis, continuous renal replacement therapy (CRRT), and other modalities are selected according to hemodynamic stability, local expertise, and fluid-management needs. In septic shock, Harrison notes that CRRT is often better tolerated because it produces less dynamic intravascular volume shift.','Bodyx'), PageBreak()]

# Page 6
story += [P('6. High-yield summary, prognosis, and references','H1x'), P('Approach to a patient with AKI','H2x'),
          tbl([['Step','Action'],['1. Confirm and stage','Compare SCr with baseline, monitor urine output, and assess the rate of deterioration.'],['2. Stabilize','Check ECG and potassium, correct immediately life-threatening hyperkalemia/acidemia, treat pulmonary edema, and consider urgent RRT.'],['3. Classify','Look for prerenal hypoperfusion, intrinsic renal disease, and postrenal obstruction. Mixed etiologies are common.'],['4. Search for cause','History, volume assessment, drug review, urinalysis/microscopy, ultrasound, and targeted investigations.'],['5. Reverse injury','Restore perfusion when appropriate, treat sepsis/shock, stop nephrotoxins, relieve obstruction, and begin disease-specific therapy.'],['6. Prevent secondary harm','Fluid and electrolyte monitoring, dose-adjust medications, nutritional support, and nephrology consultation for severe/uncertain disease.'],['7. Follow-up','Assess recovery and screen for new or worsening CKD after AKI.']], [3.2*cm,14.0*cm]),
          P('Key examination points','H2x')] + bullet(['AKI is a syndrome of abrupt functional decline and may be oliguric or non-oliguric.', 'The central differential is <b>prerenal vs intrinsic vs postrenal</b>. Treat reversible hypoperfusion and obstruction without delay.', 'Prolonged prerenal azotemia can progress to ischemic ATN.', 'Urine microscopy is diagnostically valuable; use FENa/FEUrea only as supporting evidence.', 'Do not administer excessive fluid without reassessment, particularly in heart failure, cirrhosis, sepsis, or established ATN.', 'Dialysis is for clinical indications such as refractory hyperkalemia, acidosis, pulmonary edema, uremia, or selected intoxications, not for creatinine alone.']) + [
          P('Prognosis','H2x'), P('Recovery depends on the cause, severity, duration, baseline renal reserve, and associated critical illness. Prerenal and obstructive AKI can recover rapidly if corrected early; severe intrinsic AKI, especially in sepsis or multiorgan failure, has a poorer short-term prognosis. AKI is also a marker of later CKD and cardiovascular risk, so follow-up is required.','Bodyx'),
          P('References','H2x'), P('1. Waikar SS, Bonventre JV. Acute Kidney Injury. Chapter 321. In: <i>Harrison\'s Principles of Internal Medicine</i>. 22nd ed. McGraw Hill; 2025. Source for the core content, staging table, etiologic framework, and management table in this note.','Small'),
          P('2. Kidney Disease: Improving Global Outcomes (KDIGO). <i>Clinical Practice Guideline for Acute Kidney Injury</i>. Kidney Int Suppl. 2012;2(1). The KDIGO diagnostic criteria used in Harrison are reproduced in this summary.','Small'),
          P('Educational note: This PDF is a study summary, not a substitute for clinical judgment, local protocols, nephrology input, or emergency care for a patient with suspected AKI.','Small')]

doc.build(story, onFirstPage=footer, onLaterPages=footer)
print(OUT)