Counter-Current Mechanism in the Kidney

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    Image, HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.pdfbase import pdfmetrics

OUTPUT = "/tmp/workspace/counter-current-pdf/Counter_Current_Mechanism.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2.2*cm, bottomMargin=2.2*cm,
    title="Counter-Current Mechanism",
    author="Orris Medical"
)

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

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle(
    "MyTitle",
    parent=styles["Title"],
    fontSize=22,
    leading=28,
    textColor=colors.HexColor("#1a3a5c"),
    spaceAfter=4,
)
subtitle_style = ParagraphStyle(
    "Subtitle",
    parent=styles["Normal"],
    fontSize=11,
    textColor=colors.HexColor("#5a7a9a"),
    spaceAfter=14,
    alignment=TA_CENTER,
)
h1_style = ParagraphStyle(
    "H1",
    parent=styles["Heading1"],
    fontSize=14,
    leading=18,
    textColor=colors.white,
    backColor=colors.HexColor("#1a3a5c"),
    spaceBefore=14,
    spaceAfter=6,
    leftIndent=-6,
    rightIndent=-6,
    borderPad=6,
)
h2_style = ParagraphStyle(
    "H2",
    parent=styles["Heading2"],
    fontSize=12,
    leading=15,
    textColor=colors.HexColor("#1a3a5c"),
    spaceBefore=10,
    spaceAfter=4,
    borderWidth=0,
    borderPadding=0,
)
h3_style = ParagraphStyle(
    "H3",
    parent=styles["Heading3"],
    fontSize=10.5,
    leading=13,
    textColor=colors.HexColor("#2e6da4"),
    spaceBefore=8,
    spaceAfter=3,
    fontName="Helvetica-BoldOblique",
)
body_style = ParagraphStyle(
    "Body",
    parent=styles["Normal"],
    fontSize=10,
    leading=15,
    spaceAfter=6,
    alignment=TA_JUSTIFY,
)
bullet_style = ParagraphStyle(
    "Bullet",
    parent=styles["Normal"],
    fontSize=10,
    leading=14,
    leftIndent=16,
    spaceBefore=1,
    spaceAfter=2,
    bulletIndent=4,
)
caption_style = ParagraphStyle(
    "Caption",
    parent=styles["Normal"],
    fontSize=8.5,
    leading=11,
    textColor=colors.HexColor("#555555"),
    alignment=TA_CENTER,
    spaceAfter=8,
    fontName="Helvetica-Oblique",
)
source_style = ParagraphStyle(
    "Source",
    parent=styles["Normal"],
    fontSize=8,
    leading=11,
    textColor=colors.HexColor("#777777"),
    spaceBefore=16,
    spaceAfter=2,
    fontName="Helvetica-Oblique",
)

def h1(text):
    return Paragraph(f"  {text}", h1_style)

def h2(text):
    return Paragraph(text, h2_style)

def h3(text):
    return Paragraph(text, h3_style)

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

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

def sp(n=6):
    return Spacer(1, n)

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


# ------- TABLE HELPER -------
def make_table(header, rows, col_widths=None):
    data = [header] + rows
    if col_widths is None:
        n = len(header)
        col_widths = [CONTENT_W / n] * n

    ts = TableStyle([
        # Header
        ("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), 9),
        ("ALIGN", (0, 0), (-1, 0), "CENTER"),
        ("BOTTOMPADDING", (0, 0), (-1, 0), 6),
        ("TOPPADDING", (0, 0), (-1, 0), 6),
        # Body
        ("FONTNAME", (0, 1), (-1, -1), "Helvetica"),
        ("FONTSIZE", (0, 1), (-1, -1), 9),
        ("ALIGN", (0, 1), (-1, -1), "LEFT"),
        ("VALIGN", (0, 0), (-1, -1), "MIDDLE"),
        ("TOPPADDING", (0, 1), (-1, -1), 4),
        ("BOTTOMPADDING", (0, 1), (-1, -1), 4),
        ("LEFTPADDING", (0, 0), (-1, -1), 6),
        ("RIGHTPADDING", (0, 0), (-1, -1), 6),
        # Alternating rows
        *[("BACKGROUND", (0, i), (-1, i), colors.HexColor("#eef4fb")) for i in range(2, len(data), 2)],
        ("ROWBACKGROUNDS", (0, 1), (-1, -1), [colors.white, colors.HexColor("#eef4fb")]),
        # Grid
        ("GRID", (0, 0), (-1, -1), 0.5, colors.HexColor("#aaccee")),
        ("LINEBELOW", (0, 0), (-1, 0), 1.5, colors.HexColor("#1a3a5c")),
    ])
    # Convert strings to Paragraphs for wrapping
    cell_style = ParagraphStyle("tc", parent=styles["Normal"], fontSize=9, leading=12)
    hdr_style = ParagraphStyle("th", parent=styles["Normal"], fontSize=9, leading=12,
                                fontName="Helvetica-Bold", textColor=colors.white, alignment=TA_CENTER)
    pdata = []
    for ri, row in enumerate(data):
        prow = []
        for ci, cell in enumerate(row):
            st = hdr_style if ri == 0 else cell_style
            prow.append(Paragraph(str(cell), st))
        pdata.append(prow)

    t = Table(pdata, colWidths=col_widths)
    t.setStyle(ts)
    return t


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

# Title block
story.append(sp(4))
story.append(Paragraph("Counter-Current Mechanism", title_style))
story.append(Paragraph("Renal Physiology — Urine Concentration", subtitle_style))
story.append(HRFlowable(width="100%", thickness=2, color=colors.HexColor("#1a3a5c"), spaceAfter=10))

# Intro
story.append(p(
    "The counter-current mechanism is the process by which the kidney creates a highly concentrated "
    "medullary interstitium, enabling formation of concentrated (hypertonic) urine. It has two main components: "
    "the <b>counter-current multiplier</b> (loop of Henle) and the <b>counter-current exchanger</b> (vasa recta)."
))

# ---- SECTION 1 ----
story.append(h1("1. What Is a Counter-Current System?"))
story.append(p(
    "A counter-current system is one in which inflow runs <b>parallel to, in close proximity to, and in the "
    "opposite direction of</b> outflow over some distance. Both the loop of Henle and the vasa recta function "
    "this way in the renal medulla."
))
story.append(p(
    "The goal is to maintain an <b>osmotic gradient</b> that increases progressively from the cortex "
    "(~300 mOsm/kg) down to the tip of the medullary papilla (~1200-1400 mOsm/kg). This gradient is "
    "<i>produced</i> by the loop of Henle and <i>maintained</i> by the vasa recta."
))

# ---- SECTION 2 ----
story.append(h1("2. Counter-Current Multiplier (Loop of Henle)"))
story.append(p(
    "The loop of Henle acts as a <b>multiplier</b> because a small osmotic gradient at any single level is "
    "amplified into a large gradient along the entire length of the loop by the continuous flow of tubular fluid."
))

story.append(h2("Key Structural Properties"))
story.append(make_table(
    ["Segment", "Water Permeability", "NaCl Active Transport", "Urea Permeability"],
    [
        ["Thin descending limb", "High (aquaporin-1)", "None", "Moderate"],
        ["Thin ascending limb", "None", "None (passive NaCl efflux)", "Moderate"],
        ["Thick ascending limb (TAL)", "None", "High (NKCC2 cotransporter)", "None"],
    ],
    col_widths=[5.2*cm, 4.2*cm, 5.2*cm, 3.4*cm]
))
story.append(sp(6))
story.append(p(
    "The <b>thick ascending limb (TAL)</b> is the engine of the entire system. It actively pumps Na<super>+</super>, "
    "K<super>+</super>, and Cl<super>-</super> out into the interstitium via the NKCC2 cotransporter, but is "
    "<b>completely impermeable to water</b>. This is the key distinction: it adds solute <i>without</i> losing "
    "water, thereby building up hyperosmolarity in the medullary interstitium."
))

story.append(h2("Step-by-Step Process"))
story.append(p(
    "Starting from a uniform 300 mOsm/kg throughout the loop and interstitium:"
))
steps = [
    ("<b>Step A:</b>", "Everything starts at 300 mOsm/kg throughout."),
    ("<b>Step B:</b>", "The TAL pumps NaCl out, raising interstitial osmolality to 400 mOsm/kg. The thin "
     "descending limb equilibrates (water leaves) and also reaches 400. The TAL fluid drops to 200 (lost "
     "salt, kept water)."),
    ("<b>Step C:</b>", "New isotonic fluid (300 mOsm/kg) enters the top of the descending limb from the "
     "proximal tubule, pushing concentrated fluid downward toward the tip."),
    ("<b>Step D:</b>", "Pumping resumes. The cycle repeats. The descending limb progressively concentrates "
     "as fluid moves down; the ascending limb progressively dilutes as it pumps NaCl out."),
    ("<b>Final result:</b>", "An axial gradient from ~300 mOsm/kg at the cortex to ~1200 mOsm/kg at the "
     "papillary tip. Juxtamedullary nephrons with longer loops reach higher osmolalities."),
]
for label, text in steps:
    story.append(Paragraph(f"&nbsp;&nbsp;&nbsp;&nbsp;{label} {text}", body_style))

# Figure 1
story.append(sp(8))
fig1_path = "/tmp/workspace/counter-current-pdf/fig1_multiplier.png"
img1 = Image(fig1_path, width=CONTENT_W, height=CONTENT_W * 0.52)
story.append(KeepTogether([
    img1,
    Paragraph(
        "FIGURE 1 — Operation of the loop of Henle as a counter-current multiplier (steps A-H). "
        "TDL = thin descending limb; MI = medullary interstitium; TAL = thick ascending limb. "
        "Numbers represent osmolality in mOsm/kg H\u2082O.",
        caption_style
    )
]))

# ---- SECTION 3 ----
story.append(h1("3. Role of Urea"))
story.append(p(
    "Urea contributes approximately 400-500 mOsm/kg to the medullary interstitial concentration and is "
    "essential for maximum urinary concentration:"
))
story.append(b("The inner medullary collecting duct is permeable to urea (via <b>UT-A1/UT-A3</b> transporters), "
               "especially when <b>ADH (vasopressin)</b> is present."))
story.append(b("Urea diffuses out of the collecting duct into the interstitium."))
story.append(b("It enters the thin descending limb and recycles through the loop — a process called "
               "<b>urea recycling</b> or counter-current amplification of urea."))
story.append(b("High protein diet → more urea → better concentrating ability."))
story.append(b("Low protein diet / malnutrition → reduced urea → impaired concentrating ability."))
story.append(sp(4))
story.append(p(
    "Urea transport in the collecting duct is mediated by UT-A1 and UT-A3; both are regulated by vasopressin. "
    "During antidiuresis (high vasopressin), the amount of urea deposited in the medullary interstitium "
    "increases, thus increasing the concentrating capacity of the kidney."
))

# ---- SECTION 4 ----
story.append(h1("4. Counter-Current Exchanger (Vasa Recta)"))
story.append(p(
    "The vasa recta are specialised peritubular capillaries that loop down into the medulla in parallel "
    "with the loop of Henle. They act as a <b>passive counter-current exchanger</b> that preserves the "
    "medullary osmotic gradient rather than washing it away."
))

story.append(h2("Mechanism"))
story.append(b("As blood <b>descends</b> into the medulla: NaCl and urea diffuse <b>into</b> the vessel "
               "from the concentrated interstitium; water diffuses <b>out</b>. Blood becomes progressively more concentrated."))
story.append(b("As blood <b>ascends</b> out of the medulla: the reverse occurs — NaCl and urea diffuse "
               "<b>out</b> back into the interstitium; water re-enters the vessel."))
story.append(b("Net effect: the vasa recta remove only the water reabsorbed from tubules, carrying "
               "away excess water without dissipating the osmotic gradient."))
story.append(sp(4))
story.append(p(
    "The blood returning to the cortex (osmolality ~325 mOsm/kg vs. incoming ~300 mOsm/kg) confirms "
    "a small net amount of water is removed while the gradient is maintained."
))

# Figure 2
story.append(sp(8))
fig2_path = "/tmp/workspace/counter-current-pdf/fig2_exchanger.png"
img2 = Image(fig2_path, width=CONTENT_W * 0.55, height=CONTENT_W * 0.72)
img2.hAlign = "CENTER"
story.append(KeepTogether([
    img2,
    Paragraph(
        "FIGURE 2 — Operation of the vasa recta as counter-current exchangers. NaCl and urea diffuse "
        "out of the ascending limb of the vessel and into the descending limb, whereas H\u2082O diffuses "
        "out of the descending limb into the ascending limb. Numbers = osmolality (mOsm/kg).",
        caption_style
    )
]))

# ---- SECTION 5 ----
story.append(h1("5. Collecting Duct — Final Concentration Step"))
story.append(p(
    "Once the medullary interstitium is hyperosmotic, the collecting duct traverses it from cortex to papilla. "
    "In the presence of <b>ADH</b>:"
))
story.append(b("The collecting duct epithelium inserts aquaporin-2 (AQP2) channels in response to ADH."))
story.append(b("Water moves out by osmosis into the hyperosmotic interstitium."))
story.append(b("Urine becomes progressively more concentrated, reaching up to <b>1200 mOsm/kg</b>."))
story.append(b("Without ADH: the collecting duct remains impermeable to water and dilute urine is excreted."))

# ---- SECTION 6 — Summary Table ----
story.append(h1("6. Summary"))
story.append(make_table(
    ["Component", "Structure", "Function", "Mechanism"],
    [
        ["Counter-current multiplier", "Loop of Henle (TAL)", "Creates medullary hyperosmolarity",
         "Active NaCl pump in water-impermeable TAL"],
        ["Urea recycling", "Inner medullary CD + thin descending limb", "Amplifies medullary osmolarity",
         "Urea diffusion via UT-A transporters"],
        ["Counter-current exchanger", "Vasa recta", "Preserves medullary gradient",
         "Passive exchange of NaCl, urea, and water"],
        ["Final concentrator", "Collecting duct", "Concentrates urine",
         "Water reabsorption driven by ADH / AQP2"],
    ],
    col_widths=[4.2*cm, 4.4*cm, 4.4*cm, 4.6*cm]
))

# ---- SECTION 7 — Clinical ----
story.append(h1("7. Clinical Relevance"))
story.append(make_table(
    ["Condition / Drug", "Mechanism Affected", "Clinical Effect"],
    [
        ["Loop diuretics (furosemide)", "Blocks NKCC2 cotransporter in TAL",
         "Abolishes medullary gradient → dilute urine regardless of ADH"],
        ["Central diabetes insipidus", "No ADH secretion",
         "Collecting duct impermeable → dilute polyuria (intact gradient)"],
        ["Nephrogenic DI", "ADH resistance (AQP2/V2R defect)",
         "Same dilute polyuria despite normal/high ADH"],
        ["Low protein diet / malnutrition", "Reduced urea delivery",
         "Impaired medullary osmolarity → reduced concentrating ability"],
        ["Short loops of Henle (renal disease)", "Less gradient buildup over length",
         "Impaired urinary concentration"],
    ],
    col_widths=[5.0*cm, 6.0*cm, 6.6*cm]
))

# Sources
story.append(hr())
story.append(Paragraph(
    "Sources: Ganong's Review of Medical Physiology, 26th Ed., pp. 687-688 | "
    "Guyton and Hall Textbook of Medical Physiology, pp. 373-375",
    source_style
))

# ============================================================
doc.build(story)
print("PDF built successfully:", OUTPUT)
EOF