Kidney Physiology: Nephron Function and Regulation

Renal Physiology Cheatsheet

I. Organofunctional Organization

I.1. The Nephron

• Each kidney contains approximately 1 million nephrons.
• Each nephron comprises a glomerular apparatus (Malpighian corpuscle) and a tubular system.
• Glomerular apparatus:
  • Bowman's capsule: surrounds glomerular capillaries.
  • Glomerular capillaries: site of filtration.
• Tubular system:
  • Proximal Convoluted Tubule (PCT)
  • Loop of Henle (LoH)
  • Distal Convoluted Tubule (DCT)
  • Collecting Duct (CD): opens into the renal pelvis.

I.2. Vascularization

• Blood supply via renal arteries.
• Glomerular capillaries arise from an afferent arteriole and drain into an efferent arteriole (not a venule).
• Blood from the efferent arteriole supplies peritubular capillaries and vasa recta.
• Vasa recta descend into the medulla, vascularizing the LoH and CD.
• All vessels eventually drain into renal veins.

II. Major Functions of the Kidney

1. Glomerular Filtration
2. Tubular Reabsorption
3. Tubular Secretion

II.1. Glomerular Filtration (GF)

• Mass flow of protein-free plasma from glomerular capillaries to Bowman's space.
• A passive process driven by hydrostatic pressure.
• Crucial for maintaining homeostasis.

a. Glomerular Filtrate (Ultrafiltrate)

• Composition: Similar to plasma, but lacks blood cells and large proteins.
• Small molecules like calcium may be less abundant due to protein binding.

b. Determinants of Glomerular Filtration

1. Net Filtration Pressure (effective pressure)
2. Membrane Permeability

Net Filtration Pressure Formula:

• (Capillary Hydrostatic Pressure): Causes fluid to leave capillary (55-70 mmHg).
• (Colloid Osmotic Pressure): Retains fluid in capillary (25-30 mmHg).
• (Intracapsular Pressure of Bowman): Opposes fluid entry into Bowman's capsule (10-15 mmHg).

Membrane Permeability

• Glomerular membrane: porous.
  • Easily permeable to small molecules (electrolytes, urea, glucose).
  • Slower permeation for proteins with .
  • Almost impermeable to proteins with (e.g., albumin).
• Electrical charge: Filtration slits are negatively charged, repelling negatively charged plasma proteins.

c. Glomerular Filtration Rate (GFR)

• 1/5 of renal plasma flow (RPF) is filtered, forming 125 ml/min, or 180 L/24 hours.
• Filtration Fraction (FF) = GFR/RPF = 20% (1/5).

Measurement of GFR:

• Uses substances that are filtered, but neither reabsorbed nor secreted by tubules.
• Endogenous substance: Creatinine (less accurate than exogenous).
• Exogenous substances: Inulin, Mannitol (used in animal experimentation).
• Formula: (Quantity eliminated in urine = Quantity filtered)
  • = urinary concentration of substance
  • = urinary flow rate
  • = plasma concentration of substance
  • = volume of plasma filtered per unit time (GFR)

d. Regulation of GFR

1. Intrinsic Regulation (within the kidney)

• Autoregulation: Maintains GFR relatively constant for MAP between 80 and 180 mmHg.
  • Myogenic mechanism: Afferent arteriole constriction/dilation in response to pressure changes.
  • Tubuloglomerular feedback:
    • Decreased GFR decreased NaCl in tubule.
    • Juxtaglomerular apparatus detects this reduces vasoactive substance secretion (e.g., endothelin).
    • Result: Afferent arteriole dilation increased effective pressure and GFR.
• Intra-renal hormonal systems:
  • Renin-Angiotensin System (RAS): Angiotensin II causes efferent arteriole vasoconstriction, decreasing RPF but increasing GFR.
  • Arachidonic acid derivatives (e.g., Prostaglandins PGE₂, PGD₂, PGI₂): Lead to afferent and efferent arteriole vasodilation, increasing RPF and GFR.

2. Extrinsic Regulation (systemic influences)

• Vasoconstrictor systems: Sympathetic Nervous System, Vasopressinergic system, systemic RAS.
• Vasodilator systems: Atrial Natriuretic Factor (ANF) from cardiac myocytes. Causes afferent arteriole vasodilation, increasing GFR.

II.2. Tubular Functions

• Tubular Reabsorption: Return essential water and dissolved substances to the internal environment.
• Tubular Secretion: Eliminate substances not sufficiently filtered by the glomerulus.

a. Tubular Reabsorption

1. Luminal (apical) membrane of tubular cells.
2. Tubular cell cytosol.
3. Basolateral membrane of tubular cells.
4. Interstitial fluid.
5. Capillary wall to reach the blood.

Mechanisms of Reabsorption:

• Active Mechanism:
  • Transports substances against a concentration gradient, requiring cellular work and ATP (ATPase).
  • Example: Glucose is totally reabsorbed actively (secondary active transport) in the PCT.
  • Renal threshold for glucose: At plasma glucose , glucose appears in urine.
  • TmG (Maximal Tubular Glucose reabsorption): . Achieved when plasma glucose exceeds , meaning all nephrons are saturated.
• Passive Mechanism:
  • Reabsorption occurs along chemical or electrical gradients.
  • Example: Active Na⁺ reabsorption creates gradients for passive reabsorption of Cl⁻ (electrical), H₂O (osmosis), and Urea (concentration difference).
  • 40-50% of filtered Urea is normally reabsorbed passively.

b. Tubular Secretion

• Some substances are filtered AND secreted by tubular cells.
• Occurs for foreign substances (e.g., penicillin, PAH) and plays a fundamental role in electrolyte balance.
• An active process, susceptible to saturation at high plasma concentrations.
• Example: PAH (para-amino-hippuric acid) secretion.
  • Formula: (Quantity eliminated = Quantity filtered + Quantity secreted).
  • For low plasma concentrations, elimination increases faster than filtration because secretion adds to the filtered amount.
  • Secretion Tm (maximal transfer) is reached at higher concentrations, after which the elimination curve becomes parallel to the filtered quantity plus Tm.

III. Exploration of Renal Function: Renal Clearance

III.1. Definition

• Renal clearance () of a substance: The volume of plasma cleared of that substance per unit time (L/min or mL/min).
• Formula:
  • = urinary concentration of substance
  • = urinary flow rate
  • = plasma concentration of substance

III.2. Types of Clearances

a. Substances only filtered (neither reabsorbed nor secreted)

• Measures GFR (F) directly.
• Clearance is independent of plasma concentration.
• Examples: Inulin, Mannitol (experimental); Creatinine (endogenous).
• Clearance value: .
• Formula:

b. Substances filtered and reabsorbed

• Clearance is always lower than GFR.
• Formula: (where is the reabsorbed quantity).
• Example: Glucose.
  • No clearance if below renal threshold, as UV = 0.
• Example: Urea.
  • Partially reabsorbed (passively). Clearance is and depends on urinary flow rate.

c. Substances filtered and secreted

• Clearance is always higher than GFR.
• Formula: (where is the secreted quantity).
• Example: PAH.
  • At low plasma concentrations (), PAH clearance approximates renal plasma flow (RPF) ().
  • When secretion Tm is reached (), clearance decreases and becomes parallel to filtered amount + Tm.
  • PAH Tm = .
• Fraction filtered (FF) = Inulin Clearance / PAH Clearance = .
• Renal Blood Flow (RBF) = (e.g., ).

III.3. Clinical Applications

• : Mild Renal Insufficiency
• : Moderate Renal Insufficiency
• : Severe Renal Insufficiency
• : Very Severe Renal Insufficiency
• : Incompatible with life without dialysis

IV. Role of the Kidney in Acid-Base Balance

IV.1. Characteristics of Final Urine

• Normal urinary output: .
• Urinary pH: (can range from to ).
• Normally free of protein, glucose, and bicarbonate.
• Contains: Creatinine, urea, sulfates, phosphates, ammonia, Cl⁻, Na⁺, K⁺.

IV.2. pH Regulation Mechanisms

• H⁺ Excretion:
  • Increased plasma [H⁺] tubular cells secrete more H⁺.
  • Decreased plasma [H⁺] kidneys conserve H⁺.
• HCO₃⁻ Excretion:
  • Increased plasma [H⁺] kidneys reabsorb more HCO₃⁻ (to buffer excess H⁺).
  • Decreased plasma [H⁺] kidneys reabsorb less HCO₃⁻ and eliminate more in urine.

V. Role of the Kidney in Hydro-Electrolytic Balance

V.1. Sodium ()

• of filtered Na⁺ is actively and obligatorily reabsorbed in the PCT.
• Active reabsorption in the ascending limb of LoH.
• In DCT and CD, Na⁺ reabsorption is active and regulated by Aldosterone according to body needs.

V.2. Chloride ()

• Reabsorbed passively, following Na⁺ to maintain electroneutrality.

V.3. Potassium ()

• Mainly reabsorbed actively in the PCT.
• Secreted in the DCT in competition with H⁺ and in exchange for Na⁺.
  • Hypokalemia Alkalosis (more H⁺ eliminated).
  • Hyperkalemia Acidosis (H⁺ elimination inhibited).

V.4. Water ()

• of filtered water is obligatorily and passively reabsorbed in the PCT, following osmotically active compounds (Na⁺, glucose, amino acids, Cl⁻, sulfates, phosphates).
• Urine leaving the PCT is isosmotic to plasma.
• LoH, DCT, and CD adjust water content to produce hypotonic or hypertonic final urine.

V.5. Mechanisms of Urine Concentration-Dilution

• Descending limb of LoH: Permeable to water, impermeable to electrolytes. Water exits passively.
• Ascending limb of LoH: Impermeable to water, reabsorbs Na⁺. Causes interstitial hypertonicity and tubular fluid hypotonicity.
• DCT and CD: Permeability to water is controlled by Antidiuretic Hormone (ADH).
  • Presence of ADH increased water reabsorption concentrated urine (e.g., in heat, hypovolemia, hyperosmolarity).
  • Absence of ADH decreased water reabsorption diluted urine (e.g., in cold, hypervolemia, hypoosmolarity).

a. Osmotic Diuresis

• Occurs when unreabsorbable substances (e.g., mannitol, glucose in diabetes) are filtered.
• High osmotic concentration in tubule less water reabsorption Polyuria.
• This "bound water" is obligatorily eliminated.
• Used in calculating Osmotic Clearance (): .

b. Water Diuresis

• Under ADH control.
• Example: Diabetes Insipidus (ADH deficiency or receptor insensitivity).
• Decreased plasma osmolarity or increased blood volume reduced ADH water elimination ("free water").
• Used in calculating Free Water Clearance (): .
  • If urine is isosmotic: .
  • If urine is hypertonic (concentrated): .
  • If urine is hypotonic (diluted): .

VI. Endocrine Functions of the Kidney

• Erythropoietin (EPO):
  • Secreted in response to cellular hypoxia.
  • Stimulates red blood cell production by bone marrow.
• Vitamin D:
  • Converts inactive 25(OH) vitamin D3 to active vitamin D3 in PCT cells via -hydroxylase (activity increased by PTH).
  • Active vitamin D increases intestinal and renal calcium absorption.
• Renin-Angiotensin-Aldosterone System (RAAS):
  • Renin secreted by juxtaglomerular apparatus in response to blood volume/pressure changes.
  • Renin converts Angiotensinogen to Angiotensin I.
  • Angiotensin-Converting Enzyme (ACE) converts Angiotensin I to Angiotensin II.
  • Angiotensin II:
    • Powerful vasoconstrictor.
    • Stimulates adrenal secretion of Aldosterone, promoting Na⁺ retention.