Biochemistry PCT: Organ Function Tests & Hormones

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// ===== DOCUMENT CONTENT =====

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    children: [
      new TextRun({ text: "ORGAN FUNCTION TESTS", bold: true, color: DARK_TEAL, size: 40, font: "Calibri" })
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    children: [
      new TextRun({ text: "Topics: Kidney  |  Liver  |  Thyroid  |  Adrenal  |  Cardiac", bold: true, color: ORANGE, size: 22, font: "Calibri" })
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// SECTION 1 - KIDNEY
const kidneySection = [
  heading1("1. TESTS OF KIDNEY FUNCTION"),
  spacer(),

  heading2("Overview"),
  body("The kidney is assessed through urinalysis, serum markers (urea, creatinine), protein excretion tests, and clearance studies. These tests detect early and late renal impairment."),
  spacer(),

  heading2("1.1 Urinalysis (Routine)"),
  heading3("A. Physical Characteristics"),
  makeTable(
    ["Parameter", "Normal", "Clinical Significance"],
    [
      ["Volume", "1–2 L / 24 hr", "Polyuria (>3 L) in DM, DI; Oliguria (<400 mL) in AKI"],
      ["Colour", "Pale to dark yellow", "Dark: dehydration, bilirubinuria; Red: haematuria"],
      ["Appearance", "Clear", "Turbid: infection, crystals, protein"],
      ["Specific Gravity", "1.003 – 1.030", "Low: DI, renal tubular disease; High: dehydration, SIADH"],
      ["pH", "4.5 – 8.0", "Alkaline: UTI (urease-producing bacteria), RTA; Acidic: ketoacidosis"],
    ],
    [2400, 2200, 4600]
  ),
  spacer(),

  heading3("B. Chemical Characteristics (Abnormal Constituents)"),
  makeTable(
    ["Constituent", "Condition When Found"],
    [
      ["Protein (Proteinuria)", "Nephrotic syndrome, diabetic nephropathy, glomerulonephritis"],
      ["Glucose (Glucosuria)", "Diabetes mellitus, renal tubular defects (renal glycosuria)"],
      ["Blood (Haematuria)", "Kidney stones, UTI, glomerulonephritis, malignancy"],
      ["Ketone bodies", "DKA, starvation, prolonged fasting"],
      ["Bile salts", "Obstructive jaundice"],
      ["Bile pigments (Bilirubin)", "Hepatocellular disease, obstructive jaundice"],
    ],
    [3200, 6000]
  ),
  spacer(),

  examTip("These 6 abnormal urine constituents are high-yield MCQ material. Memorise the condition associated with each one."),
  spacer(),

  heading2("1.2 Serum Urea and Creatinine"),
  body("Both increase as renal function declines, but creatinine is the preferred marker."),
  makeTable(
    ["Marker", "Normal Range", "Specificity", "Limitations"],
    [
      ["Serum Urea (BUN)", "2.5 – 7.5 mmol/L", "Low - affected by diet, hydration, catabolism, GI bleed", "Not specific to renal disease"],
      ["Serum Creatinine", "60 – 110 umol/L", "High - not affected by non-renal factors significantly", "Only rises after ~50% decline in GFR (poor sensitivity for early disease)"],
    ],
    [2200, 1800, 2600, 2600]
  ),
  spacer(),
  examTip("Creatinine = more SPECIFIC; only rises after 50% GFR loss = poor SENSITIVITY for early detection. Both facts are commonly tested."),
  spacer(),

  heading2("1.3 Proteinuria"),
  keyPoint("Normal protein excretion", "< 150 mg / 24 hours (below routine test detection limit)"),
  keyPoint("Normal albumin excretion", "< 30 mg / 24 hours"),
  keyPoint("Proteinuria defined as", "> 150 mg protein / 24 hours"),
  keyPoint("Microalbuminuria", "30 – 300 mg albumin / 24 hours"),
  spacer(),
  body("Most common cause of proteinuria:"),
  bullet("Loss of integrity of the glomerular basement membrane (GBM)"),
  bullet("Called: Glomerular Proteinuria"),
  bullet("Major protein lost: Albumin"),
  bullet("Seen in: Nephrotic syndrome, Diabetic nephropathy"),
  spacer(),
  examTip("Microalbuminuria (30–300 mg/24hr) = EARLY MARKER of renal damage in Diabetes Mellitus. This is a classic exam question."),
  spacer(),

  heading2("1.4 Creatinine Clearance & GFR"),
  body("Clearance = volume of plasma from which a compound is completely cleared by the kidney per unit time."),
  spacer(),
  formulaBox("Clearance (mL/min) = (U x V) / P"),
  body("Where:"),
  bullet("U = Urine concentration of analyte (from timed, usually 24-hr, sample)"),
  bullet("P = Plasma concentration of analyte"),
  bullet("V = Urine volume per minute = (24-hr urine volume) / (24 x 60)"),
  spacer(),

  makeTable(
    ["Compound", "GFR Marker?", "Why / Why Not"],
    [
      ["Creatinine", "Yes (practical standard)", "Endogenous, constant levels, freely filtered. BUT slightly secreted by tubules -> slightly OVERESTIMATES GFR"],
      ["Inulin", "Yes (gold standard)", "Exogenous, meets all ideal criteria: constant blood level, freely filtered, NOT reabsorbed or secreted. Requires IV infusion - impractical for routine use"],
      ["Urea", "No", "Partially reabsorbed by tubules; variable blood levels depending on diet and catabolism"],
    ],
    [2200, 2200, 4800]
  ),
  spacer(),
  examTip("Inulin clearance = GOLD STANDARD for GFR. Creatinine clearance = PRACTICAL standard but overestimates GFR (tubular secretion). Know the difference."),
  spacer(),

  pageBreakPara()
];

// SECTION 2 - LIVER
const liverSection = [
  heading1("2. LIVER FUNCTION TESTS (LFTs)"),
  spacer(),
  body("LFTs are a panel of tests used for: diagnosis, assessing prognosis, and monitoring therapy of liver disease. Each test assesses a specific aspect of liver function."),
  spacer(),

  heading2("2.1 LFT Panel Overview"),
  makeTable(
    ["Test", "What It Measures", "Elevated In", "Decreased In"],
    [
      ["Serum Bilirubin (total)", "Bilirubin metabolism", "Jaundice (all types), haemolysis", "-"],
      ["Conjugated Bilirubin", "Hepatic conjugation + excretion", "Obstructive jaundice (mainly), hepatocellular disease", "-"],
      ["Unconjugated Bilirubin", "Pre-hepatic bilirubin load", "Haemolytic anaemia, hepatocellular disease", "-"],
      ["Total Protein", "Hepatic synthesis", "Acute phase (fibrinogen)", "Cirrhosis, chronic liver disease"],
      ["Albumin", "Hepatic synthesis (specific)", "Not usually elevated", "Chronic liver disease, cirrhosis, nephrotic syndrome"],
      ["Prothrombin Time (PT)", "Coagulation factor synthesis", "Prolonged in acute liver disorders", "-"],
      ["ALT (Alanine Aminotransferase)", "Hepatocyte integrity", "Acute viral hepatitis (very high), hepatocellular disease", "-"],
      ["AST (Aspartate Aminotransferase)", "Hepatocyte / muscle integrity", "Hepatitis, MI, skeletal muscle injury", "-"],
      ["Alkaline Phosphatase (ALP)", "Biliary canaliculi / bone", "Obstructive jaundice, bone disease", "-"],
    ],
    [2200, 2200, 2800, 2000]
  ),
  spacer(),

  heading2("2.2 Bilirubin & Jaundice"),
  makeTable(
    ["Type of Jaundice", "Primary Bilirubin Elevated", "Cause"],
    [
      ["Pre-hepatic (Haemolytic)", "Unconjugated (indirect)", "Excess RBC destruction; liver conjugation overwhelmed"],
      ["Hepatocellular", "Both conjugated + unconjugated", "Impaired uptake, conjugation AND excretion (e.g. viral hepatitis, cirrhosis)"],
      ["Post-hepatic (Obstructive)", "Conjugated (direct)", "Bile duct obstruction (gallstones, carcinoma) -> backflow of conjugated bilirubin"],
    ],
    [2600, 2800, 3800]
  ),
  spacer(),
  examTip("Obstructive jaundice = conjugated bilirubin. Haemolytic = unconjugated. Hepatocellular = BOTH. This pattern is a guaranteed exam topic."),
  spacer(),

  heading2("2.3 Aminotransferases - ALT vs AST"),
  makeTable(
    ["Enzyme", "Organ Specificity", "When Elevated", "Exam Point"],
    [
      ["ALT (SGPT)", "Liver-specific", "Acute viral hepatitis (rises before jaundice), hepatocellular disease", "More SPECIFIC for liver disease"],
      ["AST (SGOT)", "Liver + Heart + Skeletal muscle", "Hepatitis, myocardial infarction, skeletal muscle injury", "Less specific; elevated in cardiac/muscle damage too"],
    ],
    [1800, 2400, 3000, 2000]
  ),
  spacer(),
  examTip("ALT is more SPECIFIC for liver disease. AST is elevated in MI and muscle injury too. ALT rises BEFORE jaundice in acute viral hepatitis."),
  spacer(),

  heading2("2.4 Alkaline Phosphatase (ALP)"),
  bullet("Elevated in obstructive jaundice (biliary obstruction)"),
  bullet("Also elevated in bone disease (not liver-specific)"),
  bullet("To distinguish liver vs bone: measure GGT (elevated in liver disease, not bone) or ALP isoenzymes"),
  spacer(),
  examTip("ALP is elevated in BOTH obstructive jaundice and bone disease. Always think: is this liver ALP or bone ALP?"),
  spacer(),

  heading2("2.5 Albumin and Prothrombin Time"),
  body("Both are markers of SYNTHETIC function of the liver:"),
  bullet("Albumin: low in chronic liver disease (cirrhosis) - reflects prolonged hepatic synthetic failure"),
  bullet("PT prolonged: in acute liver disorders - reflects failure to synthesise clotting factors (especially Factor VII, shortest half-life)"),
  spacer(),
  examTip("Albumin = CHRONIC disease marker. Prothrombin time = ACUTE disease marker. A common compare-and-contrast exam question."),
  spacer(),

  pageBreakPara()
];

// SECTION 3 - THYROID
const thyroidSection = [
  heading1("3. THYROID FUNCTION TESTS"),
  spacer(),

  heading2("3.1 Thyroid Hormones"),
  makeTable(
    ["Hormone", "Abbreviation", "Also Known As", "Iodine Atoms"],
    [
      ["Thyroxine", "T4", "Tetraiodothyronine", "4"],
      ["Triiodothyronine", "T3", "Liothyronine", "3 (more potent/active form)"],
      ["Thyroid Stimulating Hormone", "TSH (Thyrotropin)", "Pituitary hormone (controls thyroid)", "-"],
    ],
    [2500, 1800, 3000, 1900]
  ),
  spacer(),

  heading2("3.2 Thyroid Function Tests Panel"),
  body("A clinical diagnosis of thyroid disorder is confirmed by:"),
  bullet("Serum TSH (thyrotropin) - first-line, most sensitive test"),
  bullet("Free T4 (fT4) - confirms hypo/hyperthyroidism"),
  bullet("Free T3 (fT3) - when T3 thyrotoxicosis is suspected"),
  spacer(),
  body("Note: Total serum thyroxine is SELDOM measured now because:"),
  bullet("TBG (thyroid-binding globulin) changes can alter total T4 without any true thyroid disease"),
  bullet("Free hormone assays (fT4, fT3) are preferred because only free hormone is physiologically active"),
  spacer(),

  heading2("3.3 Interpretation of Thyroid Tests"),
  makeTable(
    ["Condition", "TSH", "Free T4", "Free T3", "Notes"],
    [
      ["Primary Hypothyroidism", "HIGH (up arrow)", "LOW", "LOW/Normal", "Thyroid gland failure; pituitary compensates by releasing more TSH"],
      ["Primary Hyperthyroidism", "LOW (down arrow)", "HIGH", "HIGH", "Excess thyroid hormone suppresses TSH"],
      ["Secondary Hypothyroidism", "LOW", "LOW", "LOW", "Pituitary failure (not enough TSH to drive thyroid)"],
      ["Secondary Hyperthyroidism", "HIGH", "HIGH", "HIGH", "Pituitary tumour secreting excess TSH"],
      ["Subclinical Hypothyroidism", "HIGH", "Normal", "Normal", "Early thyroid failure; fT4 still normal"],
    ],
    [2200, 1400, 1400, 1400, 2800]
  ),
  spacer(),
  examTip("TSH is the MOST SENSITIVE thyroid function test. It changes before fT4 becomes abnormal. In primary disease, TSH and fT4 move in opposite directions."),
  spacer(),

  pageBreakPara()
];

// SECTION 4 - ADRENAL
const adrenalSection = [
  heading1("4. ADRENAL FUNCTION TESTS"),
  spacer(),

  heading2("4.1 Overview"),
  body("Adrenal function tests confirm:"),
  bullet("Adrenal HYPERFUNCTION: Cushing Syndrome (excess cortisol)"),
  bullet("Adrenal HYPOFUNCTION: Addison Disease (cortisol deficiency)"),
  spacer(),

  heading2("4.2 Cortisol Diurnal Variation"),
  body("Cortisol secretion shows a characteristic diurnal (daily) rhythm:"),
  makeTable(
    ["Time", "Cortisol Level", "Clinical Relevance"],
    [
      ["Early morning (~8 AM)", "HIGHEST (peak)", "Normal diurnal peak"],
      ["Midnight", "LOWEST (nadir)", "Should be suppressed in normal individuals"],
    ],
    [2800, 3000, 3400]
  ),
  spacer(),
  keyPoint("Key principle", "Loss of diurnal variation = EARLIEST sign of adrenal hyperfunction (Cushing syndrome)"),
  spacer(),
  examTip("Loss of diurnal cortisol variation (midnight cortisol not suppressed) is the EARLIEST sign of Cushing syndrome. Do not confuse with the dexamethasone test."),
  spacer(),

  heading2("4.3 Dexamethasone Suppression Test (DST)"),
  body("Used to confirm Cushing Syndrome (adrenal hyperfunction):"),
  spacer(),
  makeTable(
    ["Step", "Action"],
    [
      ["1. Baseline", "Measure serum cortisol at 8 AM"],
      ["2. Drug administration", "Give 1 mg dexamethasone (synthetic glucocorticoid) at midnight"],
      ["3. Post-test measurement", "Measure serum cortisol again at 8 AM next morning"],
      ["4. Interpretation (Normal)", "Cortisol SUPPRESSED below 50 nmol/L - negative test (no Cushing)"],
      ["5. Interpretation (Abnormal)", "Cortisol NOT suppressed - POSITIVE test = Cushing syndrome confirmed"],
    ],
    [1800, 7400]
  ),
  spacer(),
  body("Mechanism: Dexamethasone acts on the pituitary to suppress ACTH. With less ACTH, the adrenal gland should produce less cortisol. In Cushing syndrome, cortisol secretion is autonomous and does not suppress."),
  spacer(),
  examTip("In the overnight DST: 1 mg dexamethasone at midnight -> check cortisol at 8 AM. Failure to suppress = Cushing syndrome."),
  spacer(),

  heading2("4.4 Addison Disease (Adrenal Hypofunction)"),
  bullet("Primary adrenal insufficiency: adrenal cortex destruction (autoimmune, TB, haemorrhage)"),
  bullet("Cortisol and aldosterone deficient"),
  bullet("ACTH is HIGH (pituitary tries to stimulate a failing adrenal gland)"),
  bullet("Diagnosis: Short Synacthen (ACTH stimulation) test - cortisol fails to rise after synthetic ACTH injection"),
  spacer(),
  examTip("Addison = HIGH ACTH + LOW cortisol. Cushing = LOW ACTH (if adrenal adenoma) or HIGH ACTH (if pituitary or ectopic). Know the ACTH levels!"),
  spacer(),

  pageBreakPara()
];

// SECTION 5 - CARDIAC
const cardiacSection = [
  heading1("5. CARDIOVASCULAR RISK AND CARDIAC MARKERS"),
  spacer(),

  heading2("5.1 Cardiovascular Risk Markers"),
  makeTable(
    ["Marker", "Measured By", "Purpose"],
    [
      ["Total plasma cholesterol", "Direct colorimetric assay", "Overall lipid risk assessment"],
      ["HDL cholesterol", "After LDL precipitation with divalent cation", "Cardioprotective - higher is better"],
      ["LDL cholesterol", "Calculated (Friedewald) or direct measurement", "Primary atherogenic particle - lower is better"],
      ["LDL:HDL ratio", "Calculated from above", "Best index of atherosclerosis risk (see Chapter 25)"],
    ],
    [2200, 3200, 3800]
  ),
  spacer(),

  heading2("5.2 Myocardial Infarction (MI) Markers"),
  body("An ECG may not always show typical changes following MI. In such cases, serum biomarkers confirm the diagnosis:"),
  spacer(),
  makeTable(
    ["Biomarker", "Specificity", "Timing", "Notes"],
    [
      ["Cardiac Troponin T or I", "Highly cardiac-specific", "Rises 3–6 hr; peaks 12–24 hr; stays elevated 10–14 days", "Gold standard for MI diagnosis; preferred over CK-MB"],
      ["Creatine Kinase-MB (CK-MB)", "Cardiac-specific isoenzyme", "Rises 3–6 hr; peaks 18–24 hr; returns to normal 2–3 days", "Useful when troponin unavailable; re-infarction monitoring"],
      ["Total CK", "Non-specific", "Rises early; non-specific", "Elevated in skeletal muscle injury too - avoid as sole marker"],
      ["LDH (Lactate Dehydrogenase)", "Non-specific (historical)", "Rises late (24–48 hr); peaks day 3–5", "No longer recommended for MI diagnosis"],
    ],
    [2400, 2400, 2800, 1600]
  ),
  spacer(),
  examTip("Cardiac Troponin = GOLD STANDARD for MI. CK-MB = cardiac-specific but less sensitive than troponin. Total CK and LDH are non-specific and rarely used now."),
  spacer(),

  pageBreakPara()
];

// SECTION 6 - QUICK REVIEW TABLE
const quickReviewSection = [
  heading1("6. QUICK REVIEW: ALL ORGAN FUNCTION TESTS AT A GLANCE"),
  spacer(),
  makeTable(
    ["Organ", "Key Tests", "Key Markers", "Must-Know Fact"],
    [
      ["KIDNEY", "Urinalysis, Creatinine clearance", "Serum creatinine, Urea, Albumin", "Microalbuminuria (30–300 mg/24hr) = early DM renal damage"],
      ["KIDNEY", "GFR estimation", "Inulin (gold std), Creatinine (practical)", "Creatinine overestimates GFR; inulin = ideal but requires IV infusion"],
      ["LIVER", "LFT panel", "ALT, AST, ALP, Bilirubin, Albumin, PT", "ALT more specific for liver; rises before jaundice in hepatitis"],
      ["LIVER", "Bilirubin fractionation", "Conjugated vs Unconjugated", "Obstructive = conjugated; Haemolytic = unconjugated; Hepatocellular = both"],
      ["THYROID", "Thyroid panel", "TSH, Free T4, Free T3", "TSH = most sensitive first-line test"],
      ["THYROID", "Pattern recognition", "TSH vs fT4 relationship", "Primary disease: TSH and fT4 move in OPPOSITE directions"],
      ["ADRENAL", "Overnight DST", "Cortisol before/after 1 mg dexamethasone", "No suppression = Cushing syndrome"],
      ["ADRENAL", "Diurnal cortisol", "8 AM vs midnight cortisol", "Loss of diurnal variation = earliest Cushing sign"],
      ["CARDIAC", "Lipid profile", "LDL:HDL ratio", "LDL:HDL ratio = best atherosclerosis risk index"],
      ["CARDIAC", "MI biomarkers", "Troponin, CK-MB", "Troponin = gold standard; stays elevated longest (10–14 days)"],
    ],
    [1600, 2200, 2400, 3000]
  ),
  spacer(),
  pageBreakPara()
];

// SECTION 7 - MCQ PRACTICE
const mcqSection = [
  heading1("7. PRACTICE MCQ QUESTIONS"),
  spacer(),

  heading3("Q1. Which of the following is the BEST marker of early renal damage in a patient with Type 2 Diabetes?"),
  bullet("A. Serum urea"),
  bullet("B. Serum creatinine"),
  bullet("C. Microalbuminuria"),
  bullet("D. Creatinine clearance"),
  new Paragraph({
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    children: [
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    ]
  }),
  spacer(),

  heading3("Q2. A patient has jaundice with predominantly elevated CONJUGATED bilirubin. What is the most likely cause?"),
  bullet("A. Haemolytic anaemia"),
  bullet("B. Gilbert syndrome"),
  bullet("C. Common bile duct obstruction"),
  bullet("D. Neonatal physiological jaundice"),
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    ]
  }),
  spacer(),

  heading3("Q3. Which aminotransferase is MORE SPECIFIC for liver disease and WHY?"),
  bullet("A. AST - because it is found only in liver cells"),
  bullet("B. ALT - because it is elevated only in cardiac muscle injury"),
  bullet("C. ALT - because it is not significantly elevated in cardiac or skeletal muscle injury"),
  bullet("D. AST - because it rises before jaundice in hepatitis"),
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  }),
  spacer(),

  heading3("Q4. The overnight dexamethasone suppression test: 1 mg dexamethasone is given at midnight. What result CONFIRMS Cushing syndrome?"),
  bullet("A. Cortisol suppressed below 50 nmol/L at 8 AM"),
  bullet("B. Cortisol NOT suppressed at 8 AM"),
  bullet("C. ACTH levels elevated at midnight"),
  bullet("D. Loss of cortisol diurnal variation on repeat testing"),
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  spacer(),

  heading3("Q5. A patient presents with chest pain. ECG is inconclusive. Which blood test is the GOLD STANDARD for confirming myocardial infarction?"),
  bullet("A. Serum LDH"),
  bullet("B. Total CK"),
  bullet("C. CK-MB"),
  bullet("D. Cardiac Troponin"),
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    ]
  }),
  spacer(),

  heading3("Q6. What is the ideal compound for measuring GFR and why is it not routinely used?"),
  bullet("A. Creatinine - it is reabsorbed by tubules"),
  bullet("B. Inulin - it must be infused intravenously"),
  bullet("C. Urea - it is too readily filtered"),
  bullet("D. Albumin - it is too large to be filtered"),
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  }),
  spacer(),
];

// SECTION 8 - KEY FORMULAE
const formulaeSection = [
  heading1("8. KEY FORMULAE & REFERENCE VALUES"),
  spacer(),
  heading2("Creatinine Clearance Formula"),
  formulaBox("Clearance (mL/min) = (U x V) / P"),
  bullet("U = Urinary analyte concentration (timed urine)"),
  bullet("P = Plasma analyte concentration"),
  bullet("V = Urine volume per minute = Total urine volume (mL) / 1440"),
  spacer(),

  heading2("Reference Values Summary"),
  makeTable(
    ["Test", "Normal Value", "Flag"],
    [
      ["Serum creatinine", "60 – 110 umol/L", "Elevated in renal failure"],
      ["Serum urea", "2.5 – 7.5 mmol/L", "Non-specific elevation"],
      ["Urine protein (24 hr)", "< 150 mg/24 hr", "Proteinuria if >150 mg"],
      ["Urine albumin (24 hr)", "< 30 mg/24 hr", "Microalbuminuria: 30–300 mg"],
      ["Serum albumin", "35 – 50 g/L", "Low in cirrhosis, nephrosis"],
      ["Serum ALT", "7 – 56 U/L", "Elevated in hepatocellular damage"],
      ["Serum ALP", "44 – 147 U/L", "Elevated in obstruction + bone disease"],
      ["Serum bilirubin (total)", "3 – 17 umol/L", "Jaundice > 34 umol/L"],
      ["TSH", "0.4 – 4.0 mIU/L", "Low in hyperthyroidism; High in hypothyroidism"],
      ["Morning cortisol (8 AM)", "200 – 700 nmol/L", "Loss of diurnal variation = Cushing"],
      ["Troponin I", "< 0.04 ng/mL", "Any elevation = suspect MI"],
    ],
    [3000, 2600, 3600]
  ),
  spacer(),
  body("Source: Harper's Illustrated Biochemistry, 32nd Edition | Tietz Textbook of Laboratory Medicine, 7th Ed", false, true, MED_GRAY)
];

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