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Renal Filtration & Glucose Reabsorption

Core Physiological Roles of the Kidneys

  • Excrete metabolic wastes (esp. \text{urea} & \text{creatinine})

  • Regulate systemic pH via \text{H}^+/\text{HCO}_3^- handling

  • Control blood pressure (renin–angiotensin–aldosterone, water & Na balance)

  • Produce urine = filtered & processed blood plasma

Gross Anatomy & Blood Supply

  • Location: retro-peritoneal, tucked under last rib; two fist-sized organs ≈ size of the heart

  • Renal arteries branch directly from abdominal aorta

    • Receive ≈ 25\% of total cardiac output (huge for their size)

  • Arterial branching sequence (create a mnemonic!)

    • Renal artery → Segmental → Interlobar → Arcuate → Interlobular → Afferent arteriole → Glomerulus → Efferent arteriole

  • Need to funnel high-volume blood into microscopic nephrons (≈ 10^6 per kidney)

The Nephron: Structural Road-Map

  • Functional unit; artist images often exaggerated in size

  • Major segments (proximal → distal)

    1. Renal corpuscle = Glomerulus + Bowman’s capsule

    2. Proximal convoluted tubule (PCT)

    3. Loop of Henle (descending + ascending limbs)

    4. Distal convoluted tubule (DCT)

    5. Collecting duct (beyond today’s focus)

Filtration at the Renal Corpuscle

  • Afferent arteriole wider than efferent → traffic-jam analogy → raises intraglomerular pressure → drives filtration

  • Glomerulus = “ball of yarn” (Latin); capillaries are fenestrated (“pasta strainer”)

    • Large components (RBCs, WBCs, plasma proteins like insulin) stay in blood

    • Water & small solutes (electrolytes, glucose, amino acids, bicarbonate, urea, creatinine, some small hormones e.g. hCG) pass into Bowman’s space

  • Resulting fluid = filtrate (not yet urine)

Composition of Fresh Filtrate & Fate of Solutes

  • Wanted back (must be reabsorbed):

    • Water

    • Electrolytes

    • Glucose (vital fuel)

    • Amino acids

    • \text{HCO}_3^- (acid–base balance)

  • Waste to be excreted: \text{creatinine} & \text{urea}\;(→\text{BUN})

Tubular Processing Overview

  • PCT: bulk reabsorption; only site for glucose & amino-acid recovery

  • Loop of Henle: concentrates filtrate; massive water reabsorption (descending limb) & Na reabsorption (ascending limb)

  • DCT & Collecting duct: fine-tuning (hormonal control, acid–base, water via ADH)

Glucose Reabsorption Mechanism (PCT Detail)

Cellular Architecture

  • Tubule lumen (apical side) → PCT epithelial cell → interstitium → peritubular capillary

  • Microvilli ↑ surface area

Key Transport Proteins

  1. Na/k (basolateral)

    • Antiporter; 3 Na out / 2 K in; requires ATP

    • Creates low intracellular Na “vacuum”

  2. SGLT2 (apical, always-open symporter)

    • Couples 1 Na + 1 glucose → into cell simultaneously

    • Secondary active transport (energy from Na gradient)

  3. GLUT2 (basolateral uniporter)

    • Facilitated diffusion of glucose → interstitium → blood

Transporter Taxonomy

  • Symporter (cotransporter) = moves substrates same direction (e.g., SGLT2)

  • Antiporter (counter-transporter) = moves substrates opposite directions (e.g., Na/k)

  • Gate types (voltage, ligand, mechanical, always-open) → SGLT2 is always-open

Energetic Economy

  • Only Na/k consumes ATP; all downstream glucose movement piggy-backs on the Na gradient → “strict budget physiology”

Renal Threshold & Transport Maximum (Tₘ) for Glucose

  • Filtrate [glucose] mirrors plasma [glucose] (linear relationship)

  • Renal threshold ≈ 200\;\text{mg/dL}

    • Below this: 100\% of glucose reabsorbed

  • Transport maximum (T_m) ≈ 400\;\text{mg/dL} for combined SGLT2/GLUT2 capacity

    • Between 200–400: reabsorption rate plateaus; some glucose spills into urine

    • >400: kidneys can reabsorb only \le 400\;\text{mg/dL}; remainder lost (glycosuria)

Numeric Examples (door & conveyor-belt metaphors)

  • Plasma 50 → 50 reabsorbed (0 lost)

  • Plasma 200 → 200 reabsorbed (0 lost)

  • Plasma 300 → 400 reabsorbed max? No: at 300, reabsorption <300 (slight loss)

  • Plasma 500 → 400 reabsorbed; 100 excreted

Clinical & Real-World Connections

  • Diabetes mellitus

    • Hyperglycaemia >200 → glucose starts appearing in urine (glycosuria)

    • Explains polyuria & thirst: excess glucose drags water (osmotic diuresis)

  • BUN & Creatinine blood tests = kidney function indicators (high → impaired filtration)

  • Pregnancy tests detect urinary hCG (small hormone passes filter, not reabsorbed)

  • Creatine supplements may transiently raise serum creatinine → false alarm for renal failure

Mnemonics & Analogies Recap

  • Traffic-jam / parkway merge = afferent vs efferent arteriole size → ↑ glomerular pressure

  • Pasta strainer = fenestrated glomerular capillaries

  • Doorway crowd = transporter saturation (Tₘ)

  • I Love Lucy chocolate conveyor episode = failing to wrap “all the glucose” when flow too high

Ethical & Practical Implications

  • Understanding Tₘ informs threshold values for diagnosing diabetes & setting SGLT2-inhibitor drug doses

  • Recognises how kidney energetics minimise ATP usage—relevant to ischaemia sensitivity

Key Numbers to Memorise

  • Renal blood flow ≈ 25\% cardiac output

  • Normal fasting glucose 70–100\;\text{mg/dL}

  • Renal glucose threshold ≈200\;\text{mg/dL}

  • Glucose Tₘ ≈400\;\text{mg/dL}

Forward Look (teaser for next lecture)

  • Loop of Henle water reabsorption & osmotic link to glucose (hyperglycaemia → osmotic diuresis)

  • Distal tubule hormonal control (aldosterone, ADH)