Investigations in Malabsorption Syndrome

ls /home/daytona/workspace/ 2>/dev/null || mkdir -p /home/daytona/workspace

mkdir -p /home/daytona/workspace/malabsorption-pdf

~/malabsorption-pdf/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.lib import colors
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import Image as RLImage
import urllib.request
import os

OUTPUT = "/home/daytona/workspace/malabsorption-pdf/Malabsorption_Syndrome_Investigations.pdf"

# Download the diagnostic flowchart image
img_url = "https://cdn.orris.care/cdss_images/49924f361a9e45c2cd75ed8abb9e8da72f9f5297e9cf215ff12848b38d9f09de.png"
img_path = "/home/daytona/workspace/malabsorption-pdf/flowchart.png"
if not os.path.exists(img_path):
    urllib.request.urlretrieve(img_url, img_path)
    print("Image downloaded.")

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2*cm, bottomMargin=2*cm,
    title="Investigations in Malabsorption Syndrome",
    author="Orris Medical"
)

W, H = A4
content_width = W - 4*cm

# ── Styles ──────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

title_style = ParagraphStyle(
    "Title", parent=base["Title"],
    fontSize=20, fontName="Helvetica-Bold",
    textColor=colors.HexColor("#1a3a5c"),
    spaceAfter=4, alignment=TA_CENTER,
    backColor=colors.white
)
subtitle_style = ParagraphStyle(
    "Subtitle", parent=base["Normal"],
    fontSize=10, fontName="Helvetica",
    textColor=colors.HexColor("#4a6fa5"),
    spaceAfter=12, alignment=TA_CENTER
)
h1_style = ParagraphStyle(
    "H1", parent=base["Heading1"],
    fontSize=13, fontName="Helvetica-Bold",
    textColor=colors.white,
    backColor=colors.HexColor("#1a3a5c"),
    spaceBefore=14, spaceAfter=6,
    leftIndent=-0.3*cm, rightIndent=-0.3*cm,
    borderPad=5
)
h2_style = ParagraphStyle(
    "H2", parent=base["Heading2"],
    fontSize=11, fontName="Helvetica-Bold",
    textColor=colors.HexColor("#1a3a5c"),
    spaceBefore=10, spaceAfter=4,
    borderPad=2
)
body_style = ParagraphStyle(
    "Body", parent=base["Normal"],
    fontSize=9, fontName="Helvetica",
    textColor=colors.HexColor("#222222"),
    spaceAfter=4, leading=13,
    alignment=TA_JUSTIFY
)
bullet_style = ParagraphStyle(
    "Bullet", parent=base["Normal"],
    fontSize=9, fontName="Helvetica",
    textColor=colors.HexColor("#222222"),
    spaceAfter=2, leading=13,
    leftIndent=14, bulletIndent=0
)
note_style = ParagraphStyle(
    "Note", parent=base["Normal"],
    fontSize=8.5, fontName="Helvetica-Oblique",
    textColor=colors.HexColor("#555555"),
    spaceAfter=4, leading=12,
    backColor=colors.HexColor("#f0f4fa"),
    borderPad=6, leftIndent=4, rightIndent=4
)
source_style = ParagraphStyle(
    "Source", parent=base["Normal"],
    fontSize=7.5, fontName="Helvetica-Oblique",
    textColor=colors.HexColor("#777777"),
    spaceAfter=2, leading=11
)

# ── Helper: section header ───────────────────────────────────────────────────
def section(text):
    return [
        Spacer(1, 6),
        Paragraph(f"  {text}", h1_style),
        Spacer(1, 4)
    ]

def subsection(text):
    return [Paragraph(text, h2_style)]

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

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

def note(text):
    return Paragraph(text, note_style)

def source(text):
    return Paragraph(f"<i>{text}</i>", source_style)

# ── Table style factory ──────────────────────────────────────────────────────
def make_table(data, col_widths=None, header=True):
    tbl = Table(data, colWidths=col_widths, repeatRows=1 if header else 0)
    style_cmds = [
        ("BACKGROUND", (0,0), (-1,0), colors.HexColor("#1a3a5c")),
        ("TEXTCOLOR",  (0,0), (-1,0), colors.white),
        ("FONTNAME",   (0,0), (-1,0), "Helvetica-Bold"),
        ("FONTSIZE",   (0,0), (-1,0), 8.5),
        ("FONTNAME",   (0,1), (-1,-1), "Helvetica"),
        ("FONTSIZE",   (0,1), (-1,-1), 8.5),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, colors.HexColor("#eef2f8")]),
        ("GRID",       (0,0), (-1,-1), 0.4, colors.HexColor("#aaaaaa")),
        ("VALIGN",     (0,0), (-1,-1), "TOP"),
        ("TOPPADDING", (0,0), (-1,-1), 4),
        ("BOTTOMPADDING",(0,0), (-1,-1), 4),
        ("LEFTPADDING", (0,0), (-1,-1), 5),
        ("RIGHTPADDING",(0,0), (-1,-1), 5),
        ("WORDWRAP",   (0,0), (-1,-1), True),
    ]
    tbl.setStyle(TableStyle(style_cmds))
    return tbl

# ── Build story ──────────────────────────────────────────────────────────────
story = []

# Title block
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph("Investigations in Malabsorption Syndrome", title_style))
story.append(Paragraph("A Comprehensive Clinical Reference", subtitle_style))
story.append(HRFlowable(width="100%", thickness=2, color=colors.HexColor("#1a3a5c")))
story.append(Spacer(1, 0.3*cm))

# ── 1. Diagnostic Algorithm ──────────────────────────────────────────────────
story += section("1. Diagnostic Algorithm")
story.append(body(
    "The investigation of malabsorption follows a stepwise approach. Begin with stool examination "
    "to confirm fat malabsorption, then branch into disease-specific investigations based on clinical suspicion."
))
story.append(Spacer(1, 6))
# Insert flowchart
img = RLImage(img_path, width=content_width, height=content_width*0.6)
story.append(img)
story.append(Spacer(1, 4))
story.append(note(
    "Figure: Approach to the diagnosis of malabsorption. Ab = antibody; CT = computed tomography; "
    "EIA = enzyme immunoassay; MRCP = MR cholangiopancreatography; O&P = ova and parasites; "
    "TTG = tissue transglutaminase. [Goldman-Cecil Medicine]"
))

# ── 2. Stool Examination ─────────────────────────────────────────────────────
story += section("2. Stool Examination (First-Line)")

story += subsection("2a. Stool for Ova, Parasites & Pathogens")
for b in [
    "First test if chronic diarrhea is present",
    "PCR or antigen-capture ELISA for <i>Giardia</i> and <i>Cryptosporidium</i>",
    "Multiplex PCR stool panel for broad pathogen screening",
]:
    story.append(bullet(b))
story.append(Spacer(1, 6))

story += subsection("2b. Fecal Fat Tests")
story.append(body("The cornerstone tests for confirming fat malabsorption (steatorrhea):"))
story.append(Spacer(1, 4))

fat_data = [
    ["Test", "Details / Normal Values"],
    ["Quantitative Fecal Fat\n(72-hr collection)",
     "Patient ingests 70–100 g fat/day for 2 days. Stool collected 72 hrs.\n"
     "Normal: <7 g fat/24 hr. Values >30 g/day strongly suggest pancreatic insufficiency.\n"
     "False positives: mineral oil laxatives, rectal suppositories."],
    ["Qualitative Stool Fat\n(Sudan III stain)",
     "Spot test — specific for fecal fat. Sensitivity 90%, Specificity 90%.\n"
     "Useful screening; not quantitative. Requires adequate fat intake (100 g/day)."],
    ["NMR Method",
     "Determines % fat in stool. Normal <20%. High sensitivity/specificity."],
]
story.append(make_table(fat_data, col_widths=[3.5*cm, content_width-3.5*cm]))
story.append(Spacer(1, 4))
story.append(note(
    "A negative fecal fat test points toward carbohydrate malabsorption or secretory/osmotic diarrhea. "
    "A positive test directs further workup based on clinical suspicion."
))
story.append(source("Goldman-Cecil Medicine, Table 126-6, p. 1465"))
story.append(Spacer(1, 6))

story += subsection("2c. Fecal Elastase-1")
for b in [
    "Proteolytic enzyme produced by pancreas; 5–6× concentrated in feces",
    "Cutoff: <200 µg/g stool = pancreatic insufficiency",
    "Single 100-mg stool sample is adequate; test on formed stool only",
    "Not affected by pancreatic enzyme replacement therapy",
    "Sensitive for severe insufficiency; less reliable for mild-moderate disease",
    "Superior to fecal chymotrypsin, PABA, bentiromide, and pancreolauryl tests",
]:
    story.append(bullet(b))
story.append(source("Henry's Clinical Diagnosis and Management by Laboratory Methods"))

# ── 3. Blood Tests ────────────────────────────────────────────────────────────
story += section("3. Blood Tests")

blood_data = [
    ["Investigation", "What It Detects"],
    ["CBC (Full Blood Count)", "Macrocytic anemia (B12/folate ↓), microcytic anemia (iron ↓), lymphopenia"],
    ["Serum iron, TIBC, ferritin", "Iron deficiency → proximal small bowel (duodenal) disease"],
    ["Serum B12 and folate", "B12 ↓: ileal disease or SIBO; Folate ↓: proximal mucosal disease"],
    ["Serum albumin", "Hypoalbuminemia → protein malabsorption or protein-losing enteropathy"],
    ["Prothrombin time / INR", "Prolonged if vitamin K (fat-soluble) malabsorption present"],
    ["Serum calcium, phosphate, ALP", "Hypocalcaemia + raised ALP → vitamin D deficiency, osteomalacia"],
    ["Serum vitamins A, D, E", "Fat-soluble vitamin deficiencies"],
    ["Serum magnesium, zinc", "Micronutrient deficiencies"],
    ["ESR / CRP", "General inflammatory markers; raised in IBD"],
    ["Serum cholesterol", "Low in severe fat malabsorption; absent in abetalipoproteinemia"],
    ["Anti-TTG IgA + total IgA", "Celiac disease screening; total IgA rules out false-negative TTG"],
]
story.append(make_table(blood_data, col_widths=[4.5*cm, content_width-4.5*cm]))

# ── 4. Specific Absorption Tests ──────────────────────────────────────────────
story += section("4. Specific Absorption Tests")

story += subsection("4a. D-Xylose Absorption Test")
for b in [
    "Key test to distinguish pancreatic maldigestion from mucosal (enterogenous) malabsorption",
    "Patient fasts overnight then ingests <b>25 g D-xylose</b> orally",
    "Urine collected for <b>5 hours</b>: normal excretion ≥4–5 g; abnormal if <3 g",
    "D-xylose absorbed passively in small intestine — does NOT require pancreatic enzymes",
    "Low urine excretion → <b>mucosal disease</b> (e.g., celiac disease, Whipple's)",
    "Normal urine excretion → suggests <b>pancreatic insufficiency</b> (intact mucosa)",
    "In renal disease: measure <b>serum D-xylose at 2 hours</b> instead",
    "False positives: renal dysfunction, ascites, bacterial overgrowth (bacteria metabolize xylose)",
]:
    story.append(bullet(b))
story.append(source("Henry's Clinical Diagnosis and Management, p. 281"))
story.append(Spacer(1, 6))

story += subsection("4b. Schilling Test (Vitamin B12 Absorption)")
for b in [
    "Oral radioactive B12 given, followed by intramuscular non-radioactive B12 (flushing dose)",
    "Radioactivity measured in 24-hour urine",
    "<b>Stage 1</b> (B12 alone): Abnormal in ileal disease, SIBO, or intrinsic factor deficiency",
    "<b>Stage 2</b> (B12 + intrinsic factor): Correction → pernicious anemia/gastric disease; No correction → ileal disease",
    "Largely replaced by serum B12 testing but conceptually important",
]:
    story.append(bullet(b))
story.append(source("Henry's Clinical Diagnosis and Management, p. 283"))
story.append(Spacer(1, 6))

story += subsection("4c. Breath Tests")
breath_data = [
    ["Breath Test", "Principle", "Diagnoses"],
    ["H₂ breath test\n(lactulose/glucose)",
     "Bacteria ferment unabsorbed sugars → H₂ exhaled",
     "SIBO: early H₂ rise <90 min\n(50 g glucose: sensitivity 90%)"],
    ["H₂ breath test\n(lactose)",
     "Rise in H₂ after lactose ingestion",
     "Lactase deficiency"],
    ["H₂ breath test\n(fructose/sucrose)",
     "Rise in H₂",
     "Carbohydrate malabsorption"],
    ["¹⁴C-glycerol trioleate\nbreath test",
     "Labeled TG ingested; ↓ ¹⁴CO₂ = fat malabsorption",
     "Steatorrhea; 2-stage test ± enzymes differentiates pancreatic vs. mucosal"],
    ["¹⁴C/¹³C D-xylose\nbreath test",
     "Alternative to urine xylose",
     "Small bowel mucosal disease"],
    ["Bile acid\n¹⁴C-cholylglycine test",
     "Deconjugated by bacteria → ¹⁴CO₂",
     "Bile acid malabsorption, SIBO"],
]
story.append(make_table(breath_data, col_widths=[3.5*cm, 5.5*cm, content_width-9*cm]))
story.append(source("Goldman-Cecil Medicine, Table 126-6; Yamada's Textbook of Gastroenterology 7th Ed."))

# ── 5. Disease-Specific Tests ─────────────────────────────────────────────────
story += section("5. Disease-Specific Tests")

story += subsection("5a. Pancreatic Insufficiency")
for b in [
    "<b>Fecal elastase-1</b>: <200 µg/g stool (see Section 2c)",
    "<b>Secretin stimulation test</b>: Gold standard — duodenal intubation; measures HCO₃⁻ and enzymes after IV secretin; sensitive but invasive",
    "<b>Secretin-enhanced MRCP</b>: Spleen:pancreas signal ratio; sensitivity 77%, specificity 83% for exocrine dysfunction",
    "<b>Abdominal X-ray/CT</b>: Pancreatic calcifications (30–40% of alcohol-related chronic pancreatitis)",
    "<b>Sweat chloride test</b>: For cystic fibrosis (main cause of pancreatic insufficiency in children)",
]:
    story.append(bullet(b))
story.append(Spacer(1, 6))

story += subsection("5b. Celiac Disease")
for b in [
    "<b>Anti-tissue transglutaminase (anti-TTG) IgA</b>: Best initial serological test",
    "<b>Total serum IgA</b>: Must check to exclude IgA deficiency (causes false-negative TTG)",
    "<b>Anti-endomysial antibody (EMA)</b>: High specificity",
    "<b>Anti-deamidated gliadin peptide (DGP) IgG</b>: Used when IgA deficient",
    "<b>Duodenal biopsy (gold standard)</b>: Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis",
]:
    story.append(bullet(b))
story.append(Spacer(1, 6))

story += subsection("5c. Bacterial Overgrowth (SIBO)")
for b in [
    "<b>Quantitative culture of jejunal aspirate</b>: Gold standard — >10⁴ CFU/mL of coliform/aerobic organisms",
    "<b>Glucose/lactulose H₂ breath test</b>: Early H₂ peak within 90 min; false positives with rapid transit",
    "<b>CT/MR enterography</b>: Structural abnormalities predisposing to overgrowth (diverticula, strictures)",
]:
    story.append(bullet(b))

# ── 6. Imaging ────────────────────────────────────────────────────────────────
story += section("6. Imaging")

imaging_data = [
    ["Investigation", "Indication"],
    ["CT abdomen", "Pancreatic calcifications, structural lesions, lymphadenopathy, bowel wall thickening"],
    ["MR enterography", "Mucosal disease of small bowel, Crohn's disease; no radiation — preferred over barium"],
    ["MRCP", "Pancreatic duct anatomy, biliary disease"],
    ["Small bowel barium study", "Transit time assessment, diverticula, strictures, mucosal fold pattern"],
    ["Somatostatin receptor\nscintigraphy / PET dotatate",
     "Neuroendocrine tumors (carcinoid, VIPoma, gastrinoma) causing secretory diarrhea"],
]
story.append(make_table(imaging_data, col_widths=[4.5*cm, content_width-4.5*cm]))

# ── 7. Endoscopy & Biopsy ─────────────────────────────────────────────────────
story += section("7. Endoscopy and Biopsy")
for b in [
    "<b>Upper GI endoscopy with multiple duodenal biopsies</b>: Proximal mucosal disease (celiac, Whipple's, giardiasis, eosinophilic enteritis)",
    "<b>Colonoscopy with biopsies</b>: Distal disease, microscopic colitis",
    "<b>Capsule endoscopy</b>: Mucosal lesions in middle and distal small bowel missed on standard endoscopy",
]:
    story.append(bullet(b))

story.append(Spacer(1, 6))
story += subsection("Key Histological Findings")
histo_data = [
    ["Finding", "Diagnosis"],
    ["Villous atrophy + crypt hyperplasia + intraepithelial lymphocytes", "Celiac disease"],
    ["PAS-positive foamy macrophages + dilated lacteals (H&E)", "Whipple disease (Tropheryma whipplei)"],
    ["Lymphangiectasia (dilated lymphatics)", "Protein-losing enteropathy"],
    ["Fat globules inside enterocytes; absent beta-lipoprotein", "Abetalipoproteinemia"],
    ["Granulomas + skip lesions + transmural inflammation", "Crohn's disease"],
]
story.append(make_table(histo_data, col_widths=[7*cm, content_width-7*cm]))
story.append(source("Yamada's Textbook of Gastroenterology 7th Ed., p. 3401–3418"))

# ── 8. Other Specialized Tests ────────────────────────────────────────────────
story += section("8. Other Specialized Tests")

other_data = [
    ["Test", "Purpose"],
    ["Serum gastrin", "Zollinger-Ellison syndrome (excess acid inactivates lipase)"],
    ["Serum VIP, chromogranin A, urine 5-HIAA", "Neuroendocrine tumors (VIPoma, carcinoid)"],
    ["Serum calcitonin, glucagon, somatostatin", "Medullary thyroid carcinoma, glucagonoma, somatostatinoma"],
    ["Serum beta-lipoprotein", "Absent in abetalipoproteinemia"],
    ["Serum immunoglobulins", "Agammaglobulinemia → susceptibility to Giardia"],
    ["Lactulose-mannitol intestinal permeability test", "Mucosal integrity assessment"],
    ["Fecal calprotectin", "Differentiates IBD from IBS; monitors disease activity"],
    ["Fecal alpha-1 antitrypsin", "Protein-losing enteropathy"],
]
story.append(make_table(other_data, col_widths=[5.5*cm, content_width-5.5*cm]))

# ── 9. Summary Quick Reference ────────────────────────────────────────────────
story += section("9. Summary — Quick Reference")

summary_data = [
    ["Category", "Key Test", "Main Purpose"],
    ["Stool", "Fecal fat (quantitative/qualitative), Sudan stain", "Confirm steatorrhea"],
    ["Stool", "Fecal elastase-1", "Pancreatic insufficiency"],
    ["Stool", "O&P, Giardia EIA/PCR", "Infectious cause"],
    ["Blood", "CBC, iron, B12, folate, albumin, PT", "Nutritional deficiencies"],
    ["Blood", "Anti-TTG IgA + total IgA", "Celiac disease"],
    ["Absorption", "D-xylose test", "Mucosal vs. pancreatic malabsorption"],
    ["Absorption", "Schilling test", "B12 absorption / ileal function"],
    ["Breath", "H₂ breath test", "SIBO, lactose/carbohydrate malabsorption"],
    ["Breath", "¹⁴C-trioleate breath test", "Fat absorption"],
    ["Pancreas", "Secretin test / secretin-MRCP / fecal elastase", "Exocrine pancreatic function"],
    ["Imaging", "CT/MR enterography", "Structural small bowel disease"],
    ["Endoscopy", "Duodenal biopsy", "Mucosal disease (celiac, Whipple's)"],
]
story.append(make_table(
    summary_data,
    col_widths=[3*cm, 7*cm, content_width-10*cm]
))

# ── Sources ────────────────────────────────────────────────────────────────────
story.append(Spacer(1, 8))
story.append(HRFlowable(width="100%", thickness=1, color=colors.HexColor("#aaaaaa")))
story.append(Spacer(1, 4))
story.append(Paragraph("<b>Sources</b>", body_style))
for src in [
    "Goldman-Cecil Medicine, International Edition, 26th Ed. (Table 126-6, p. 1465)",
    "Henry's Clinical Diagnosis and Management by Laboratory Methods (pp. 271–285)",
    "Sleisenger and Fordtran's Gastrointestinal and Liver Disease",
    "Yamada's Textbook of Gastroenterology, 7th Ed.",
    "Frameworks for Internal Medicine",
]:
    story.append(source(f"• {src}"))

# ── Build ──────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUTPUT}")