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Renal Physiology - Concise Summary (GK Pal Style)

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1. Functional Anatomy of the Kidney

• Glomerulus - a capillary tuft invaginating into Bowman's capsule
• Renal tubule - proximal convoluted tubule (PCT) → proximal straight tubule → loop of Henle (thin descending limb, thin ascending limb, thick ascending limb/TAL) → distal convoluted tubule (DCT) → collecting duct

• Superficial cortical nephrons - glomerulus in outer cortex, short loop of Henle (does not reach inner medulla)
• Juxtamedullary nephrons - glomerulus near corticomedullary junction, long loop of Henle (penetrates deep into inner medulla) - responsible for urinary concentration

• Afferent arteriole diameter > efferent arteriole diameter
• Total renal blood flow (RBF) = ~1200 mL/min (~20-25% of cardiac output)
• Renal plasma flow (RPF) = ~660 mL/min

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2. Renal Clearance

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3. Glomerular Filtration

Glomerular Filtration Barrier (3 layers):

1. Endothelium - fenestrated pores 70-100 nm; bars blood cells but not proteins
2. Basement membrane (GBM) - 3 layers (lamina rara interna, lamina densa, lamina rara externa); most important barrier to proteins; negatively charged
3. Epithelium (podocytes) - foot processes with filtration slits 25-60 nm bridged by slit diaphragms

Starling Forces Governing GFR:

• PGC = glomerular capillary hydrostatic pressure (~60 mmHg) - favors filtration
• PBS = Bowman's space hydrostatic pressure (~18 mmHg) - opposes filtration
• πGC = glomerular capillary oncotic pressure (~32 mmHg) - opposes filtration
• πBS = Bowman's space oncotic pressure (~0 mmHg) - negligible

Regulation of GFR:

Autoregulation of RBF and GFR:

• Maintained over a wide range of arterial pressure (80-180 mmHg)
• Mechanisms: myogenic mechanism (stretch-induced vasoconstriction of afferent arteriole) and tubuloglomerular feedback (macula densa senses ↑NaCl delivery → afferent arteriole constriction)

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4. Tubular Reabsorption and Secretion

• Filtered load = GFR × [P]x
• Excretion rate = V × [U]x
• Reabsorption rate = Filtered load - Excretion rate (if filtered > excreted)
• Secretion rate = Excretion rate - Filtered load (if excreted > filtered)

Proximal Convoluted Tubule (PCT):

• Reabsorbs 67% of filtered Na+, water, K+, HCO3-, Cl-, urea, phosphate
• Reabsorbs 100% of filtered glucose and amino acids (under normal conditions)
• Isosmotic reabsorption - tubular fluid osmolarity remains equal to plasma (~285 mOsm/L) throughout PCT; [TF/P]Na+ = 1.0
• Brush border (microvilli) on luminal surface maximizes surface area
• Early PCT: Na+-H+ exchanger + Na+-glucose cotransport + Na+-amino acid cotransport
• Late PCT: Na+-H+ exchanger + Cl⁻-formate exchanger (reabsorbs NaCl); lumen becomes slightly positive (+4 mV)
• The Na+-K+-ATPase on the basolateral membrane is the primary driver of all reabsorption

• SGLT2 (PCT): reabsorbs 90% of filtered glucose (low affinity/high capacity)
• SGLT1 (late PCT): reabsorbs remaining 10%
• Transport maximum (Tm) for glucose ~375 mg/min; threshold (splay) ~200 mg/dL plasma concentration
• Above threshold → glucosuria (as in diabetes)

Loop of Henle:

• TAL reabsorbs ~25% of filtered NaCl
• Because TAL is impermeable to water, tubular fluid becomes hyposmotic (~100 mOsm) by the end - this is the diluting segment
• TAL generates the medullary interstitial concentration gradient (countercurrent multiplication)

Distal Convoluted Tubule (DCT):

• Impermeable to water (unless ADH present)
• Na+-Cl- cotransporter (NCC) on luminal membrane - target of thiazide diuretics
• Reabsorbs ~5-8% of filtered NaCl
• Fine-tuning of Ca2+ reabsorption (PTH and vitamin D stimulate)

Collecting Duct:

• Principal cells: reabsorb Na+ (via ENaC, epithelial Na+ channel) and water (via AQP2, stimulated by ADH); secrete K+ (via ROMK channel)
• Intercalated cells (alpha): secrete H+ (H+-ATPase and H+-K+-ATPase) and reabsorb K+; important for acid-base regulation
• Intercalated cells (beta): secrete HCO3- (for alkalosis correction)
• Aldosterone: ↑ ENaC and Na+-K+-ATPase expression → ↑ Na+ reabsorption, ↑ K+ secretion, ↑ H+ secretion
• ADH (vasopressin): inserts AQP2 water channels → ↑ water reabsorption

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5. Sodium Balance

• ECF volume expansion → ↓aldosterone, ↑ANP → ↑Na+ excretion (natriuresis)
• ECF volume contraction → ↑renin-angiotensin-aldosterone (RAAS) → ↑Na+ reabsorption

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6. Potassium Balance

• ~98% of body K+ is intracellular (maintained by Na+-K+-ATPase)
• Plasma K+ = 3.5-5.0 mEq/L

• Filtered at glomerulus (freely)
• PCT reabsorbs ~65% (passive, follows Na+)
• TAL reabsorbs ~25% (NKCC2)
• Collecting duct is the main site of regulated K+ excretion/secretion (principal cells)

1. Aldosterone - ↑ ENaC → more Na+ enters → lumen more negative → K+ secretion ↑
2. Plasma K+ concentration - ↑K+ directly stimulates aldosterone secretion and principal cell secretion
3. Tubular flow rate - ↑flow → dilutes luminal K+ → maintains gradient for secretion
4. Acid-base status - alkalosis → ↑K+ secretion; acidosis → ↓K+ secretion (H+ and K+ compete)

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7. Urine Concentration and Dilution (Countercurrent Mechanism)

Countercurrent Multiplier (Loop of Henle):

• The loop of Henle acts as a countercurrent multiplier to build up the medullary interstitial osmotic gradient (300 mOsm in cortex → 1200 mOsm in papilla)
• Mechanism:
  1. TAL actively pumps NaCl out (NKCC2) but is impermeable to water → NaCl accumulates in medullary interstitium
  2. Thin descending limb is water-permeable → water exits into the hyperosmotic interstitium → tubular fluid becomes concentrated
  3. This cycle repeats as fluid flows down and up the loop, multiplying the gradient
• Urea also contributes to inner medullary hyperosmolarity: Collecting duct (in presence of ADH) becomes permeable to urea → urea recirculates into inner medullary interstitium

Countercurrent Exchange (Vasa Recta):

• The hairpin loop arrangement of vasa recta prevents "washing out" of the medullary gradient
• Blood descending → picks up NaCl and loses water (becomes concentrated); blood ascending → loses NaCl and gains water (becomes dilute)
• Net effect: medullary gradient is preserved

ADH (Vasopressin) - Key Regulator:

• Released from posterior pituitary in response to: ↑plasma osmolarity (primary), ↓ECF volume, pain, nausea
• Acts on V2 receptors in collecting duct → cAMP → inserts AQP2 into luminal membrane
• Also increases urea permeability of inner medullary collecting duct
• With ADH (antidiuresis): tubular fluid equilibrates with hyperosmotic interstitium → small volume of concentrated urine
• Without ADH (diuresis): collecting duct is impermeable to water → large volume of dilute urine

Summary of Tubular Fluid Osmolarity Along the Nephron:

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8. Diuretics - Mechanisms and Sites of Action

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9. Renal Acid-Base Regulation

1. Reabsorbing filtered HCO3- (mainly PCT via H+ secretion)
2. Excreting excess H+ as titratable acid (H₂PO₄-) and ammonium (NH4+)

• CO2 + H2O → H2CO3 → H+ + HCO3- (catalyzed by carbonic anhydrase)
• H+ secreted into lumen via Na+-H+ exchanger
• HCO3- exits basolaterally via Na+-HCO3- cotransporter
• Luminal H+ + HCO3- → H2CO3 → CO2 + H2O (luminal carbonic anhydrase); CO2 re-enters cell

• Glutamine → NH3 + HCO3- (in PCT cells)
• NH3 + H+ → NH4+ (trapped in lumen, excreted)
• Increased in acidosis (adaptive response)

• H+-ATPase and H+-K+-ATPase secrete H+
• Stimulated by aldosterone and low plasma pH

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10. Key Numbers to Remember

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Quick Concept Recap

• PCT = bulk reabsorption (67%), isosmotic, glucose/AA/HCO3-
• Thin descending = water out (concentrated fluid)
• TAL = NaCl out, water stays = diluting segment + builds medullary gradient
• DCT = fine NaCl reabsorption (thiazide target), Ca2+ regulation
• Collecting duct = final regulation by ADH (water) and aldosterone (Na+/K+/H+)
• ADH absent → dilute urine; ADH present → concentrated urine
• Aldosterone → ↑Na+ reab, ↑K+ excretion, ↑H+ excretion
• Angiotensin II → efferent >> afferent constriction → protects GFR

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