Kidney Function and Body Fluid Regulation

Posted on Feb 26, 2025 in Biology

Kidney Functions

1. Regulation of water and electrolyte balance.
2. Regulation of arterial pressure and body fluid volume via the Renin-angiotensin-aldosterone system.
3. Excretion of metabolic waste and foreign substances.
4. Regulation of red blood cell production through erythropoietin.
5. Regulation of acid-base balance.
6. Regulation of Vitamin D production and calcium/phosphate balance.
7. Gluconeogenesis.

Kidney Structure

Three distinct zones:

• Cortex: Outer layer; site of glomerular filtration and convoluted tubules.
• Medulla: Inner layer; location of the longer loops of Henle.
• Pelvis: Drainage of the collecting ducts into the renal pelvis and ureter.

Glomerular Filtration Components

• Glomerular capillaries: A tuft of interconnected capillaries where plasma is filtered.
• Bowman’s Capsule: The beginning of the tubular system; a blind epithelial sac where filtrate collects.

Tubule Segments

• Proximal tubule: Drains the Bowman’s capsule (convoluted and straight sections).
• Loop of Henle: Thin descending limb, thin ascending limb, thick ascending limb.
• Distal tubule: Specialized section is the macula densa.
• Collecting duct: Cortical and medullary sections.
• Pelvis and out to the bladder.

Renal Blood Flow and Filtration

Renal blood flow is approximately 1.2 L/min (renal plasma flow ~650 ml plasma/min), which is 20-25% of cardiac output, despite the kidneys representing only 1-2% of total body weight. This high flow rate ensures:

• High rate of plasma filtration.
• Entire plasma volume (~3L) filtered ~60 times a day.
• Precise and rapid control of body fluid volume and composition.

Glomerular Filtration Rate (GFR): ~125 ml/min or 180 L/day (the volume of plasma filtered per minute).

Filtration fraction: ~20% (the fraction of renal plasma flow filtered in the glomerulus = GFR/Renal Plasma flow). FF = 125 ml/min / 650 ml/ml= 0.2. This is regulated and can be increased or decreased.

Juxtaglomerular Apparatus

The distal convoluted tubule touches its own glomerulus. Key components include:

• Specialized granular cells in the afferent arteriole wall that secrete renin.
• The macula densa.
• Mesangial cells.
• Efferent arteriole.

Macula Densa (MD): Densely packed cells in the distal tubule adjacent to the afferent arteriole. The MD senses changes in solute concentration in the distal tubule.

Urine Formation and Excretion

Collecting ducts lead to the renal pelvis, then to the ureter, bladder, and urethra.

• Ureter: ~25 cm long; uses peristalsis.
• Bladder: Fills and stretches; capacity of 700-800ml.

Micturition Reflex

Stretch receptors in the bladder wall trigger action potentials carried along pelvic nerves to the sacral spinal cord. Parasympathetic nerves contract the bladder’s smooth muscles. Reduced action potentials in somatic motor nerves cause the external urinary sphincter to relax. Voluntary control is learned.

Glomerular Filtration Characteristics

Glomerular capillaries are more efficient filters than other capillaries due to:

• Large fenestrations.
• High hydrostatic pressures (55 mmHg vs. 18 mmHg).

Filtration is size and charge selective:

• Small molecules (<5000 MW) are freely filtered.
• Molecules >70,000 MW are essentially blocked.
• Most proteins are repelled due to negative charge.

Filtrate in Bowman’s Capsule is virtually identical to plasma but essentially protein-free (0.02%).

Filtration Process

• Passive and non-selective: Small molecules (water, ions, glucose, amino acids) pass freely.
• Larger molecules (proteins) cannot freely cross. Protein in the urine indicates a renal problem.
• Glomerular filtration rate (GFR): The volume of filtrate formed each minute. GFR is directly proportional to the net filtration pressure.

Autoregulation of RBF and GFR

RBF (Renal Blood Flow) and GFR are autoregulated. This means the kidney maintains nearly constant blood flow despite changes in arterial pressure. Urine flow is *not* autoregulated; it is directly proportional to arterial pressure (pressure-natriuresis). Normal urine flow is 1 ml/min but can increase to 15 ml/min.

Mechanisms of Autoregulation

• Myogenic mechanism: Increased blood pressure causes afferent arterioles to constrict, decreasing blood flow and pressure to the glomerulus, normalizing glomerular pressure and keeping GFR constant.
• Tubuloglomerular feedback: Signals from the macula densa.

Reabsorption and Secretion

Reabsorption: Movement of fluid from the tubule to the peritubular capillaries.

• Quantitatively large: Plasma volume is ~3L, GFR is 125 ml/min (180 L/day). Without tubular reabsorption, the whole plasma volume and essential solutes would be excreted within 30 minutes.
• Selective: Some substances are almost completely reabsorbed; many ions are highly reabsorbed; waste products are poorly reabsorbed.

Secretion: Movement of fluid from the peritubular capillaries to the tubule.

• A second pathway into luminal fluid.
• Disposes of substances not in filtrate (e.g., drugs like penicillin).
• Eliminates undesirable substances reabsorbed passively (e.g., urea).
• Rids the body of excessive K+.
• Controls blood pH.

Sodium Reabsorption

Na-K-ATPase pumps on basolateral membranes hydrolyze ATP and use the energy:

• Na+ is pumped out of the cell into the interstitium.
• K+ is pumped from the interstitium into the cell.
• This creates a low intracellular Na+ concentration (12 mEq/L) compared to the tubular lumen (140 mEq/L).
• A net negative intracellular charge facilitates passive diffusion of Na+ into the cell via carrier-mediated facilitated diffusion.

Glucose Reabsorption

The energy required to transport substances against their concentration gradient comes from the Na+-K+-ATPase pump. Other examples include amino acids, lactate, vitamins, and most cations. The transport systems are generally quite specific. Co-transported substances move by diffusion through the basolateral membrane into peritubular capillaries.

For most actively reabsorbed (or secreted) substances, there is a limit to the transport rate, known as the Transport Maximum (Tm; mg/min).

Proximal Tubule Reabsorption

The proximal tubule has a high capacity for active and passive reabsorption, driven by Na,K-ATPase pumps:

• ~65% of H2O and Na+; 50% of Cl-; 90% of HCO3, >90% of K+ are reabsorbed.
• Sodium is co-transported with organic nutrients and counter-transported with hydrogen ions.
• Nearly all glucose, lactate, and amino acids are reabsorbed.
• Water follows sodium since the proximal tubule is highly permeable to water (~65% reabsorbed).

Loop of Henle

The loop of Henle has three distinct sections. Tubular fluid entering the loop is iso-osmotic to plasma. More sodium (25% of the filtered load) than water (10%) is reabsorbed. Tubular fluid at the end of the loop is hypotonic compared to plasma.

1. Thin Descending Limb: Thin epithelial cells, no brush border, few mitochondria; highly permeable to water. 10% of filtered water is reabsorbed due to the medullary interstitial concentration gradient. No active Na+ reabsorption; simple diffusion of some solutes (e.g., urea and Na+).
2. Thin Ascending Limb: Low reabsorptive capacity; virtually impermeable to water.
3. Thick Ascending Limb: Na-K ATPase in basolateral membranes facilitates movement of Na+ across the luminal membrane via a 1Na+, 2Cl-, 1K+ cotransporter. Reabsorbs 25% of filtered NaCl, K+, Ca2+, and HCO3- almost exclusively in this limb.

Late Distal Tubule and Collecting Duct

Reabsorption in this region depends on the body’s needs and is regulated by hormones. There are two types of cells in the collecting ducts:

• Intercalated cells
• Principal cells

The fluid in the lumen is hypo-osmotic (dilute urine).

• Sodium: Energy is supplied by Na+-K+-ATPase. Reabsorbed with a Cl- symporter. Only 3-5% of filtered Na+ remains to be reabsorbed, dependent on aldosterone.
• Water: Normally impermeable; dependent on antidiuretic hormone (ADH; vasopressin). When ADH is present, water moves out of the tubules by osmosis.

Fluid Compartments

• Intracellular Fluid (ICF): 60% of total body water (TBW); fluid within cells. The selective cell membrane is highly permeable to water but not to most electrolytes.
• Extracellular Fluid (ECF): 40% of TBW; fluid outside cells. Includes blood (10% TBW), interstitial fluid, lymph, and transcellular fluid (a specialized type of ECF).

Adding salt to a compartment draws water into that compartment.

Fluid Imbalances

• Dehydration: Water loss exceeds water intake. Sweat has a lower osmolarity than plasma.
• Hemorrhage: Isotonic fluid loss; decreased ECF volume, but no change in osmolarity. ICF is unchanged.
• Hypotonic Hydration: Cellular overhydration due to kidney damage or water intoxication. Increased ECF and ICF volume, and decreased osmolarity.
• Edema: Isotonic fluid gain; accumulation of fluid in the interstitial space. May or may not increase plasma volume. Causes include congestive heart failure, kidney disease, liver disease, and burns.

Fluid Balance Regulation

Receptors

• Fluid Composition: Osmoreceptors in the hypothalamus (ADH release) and adrenal gland (zona glomerulosa cells; aldosterone release).
• Fluid Volume:
  • Peripheral volume receptors (autonomic nervous system): Baroreceptors (high pressure) in the aortic arch and carotid artery; stretch receptors (cardio-pulmonary) in the atria, ventricles, and pulmonary vessels.
  • Renal baroreceptors: Cells of the afferent arteriole in the juxtaglomerular region (release renin).

Hormonal Control

Aldosterone: A mineralocorticoid released by the adrenal cortex (zona glomerulosa cells) in response to:

• Increased plasma K+.
• Increased angiotensin II.
• Plasma Na+ has no effect.

Aldosterone acts on the renal distal tubule to increase Na+ reabsorption.

Renin: Released by renal baroreceptors; release decreases as arterial pressure increases.

Thirst Mechanism

Thirst is triggered by two stimuli and functions to replace fluid loss:

1. Dehydration: Decreased ECF osmolarity causes osmoreceptor cells in the hypothalamus to shrink, signaling the cerebral cortex and giving rise to the sensation of thirst. This also reflexly decreases salivary and buccal gland secretions, causing a dry mouth and throat. This is a very sensitive mechanism; changes in plasma osmolarity of only 1-2% are required.
2. Decreased Blood Volume: Stimulation of volume (baroreceptors) and stretch receptors (atrial and pulmonary) stimulates the thirst control centers in the hypothalamus. This is a less sensitive mechanism, requiring a 10-15% change in blood volume.

ADH and Water Reabsorption

ADH (Antidiuretic Hormone) is delivered via the blood (peritubular capillaries) and stimulates V2 receptors on the basolateral membrane of the collecting duct. This activates adenyl cyclase, causing a cascade that inserts aquaporins into the luminal membrane, increasing water reabsorption (the urine is hypotonic compared to body fluids at this point).

Sodium Intake and Output

Situation: Decreased sodium intake.

Problem: Mismatch between sodium intake and output, leading to reduced plasma osmolarity.

Solution:

1. Remove excess water to restore plasma osmolarity.
2. Address the resulting reduced blood volume.

Antidiuretic Hormone (ADH)

ADH increases the water permeability of the distal tubule and collecting duct. Osmoreceptors in the hypothalamus are stimulated by changes in plasma osmolarity and volume. ADH is released by the posterior pituitary in response to increased plasma osmolarity. ADH increases collecting duct permeability to water by inserting aquaporins. A concentration gradient has been built up, so water follows this gradient, and additional sodium is also reabsorbed.

Diabetes Insipidus (DI)

• Central DI (Neurogenic DI): ADH cannot be produced or released.
• Nephrogenic DI: ADH secretion is normal, but the kidney does not respond correctly.

Pressure Diuresis/Natriuresis

The rate of urine excretion is directly related to arterial pressure (pressure natriuresis and pressure diuresis). This is mediated by changes in tubular sodium reabsorption. RBF and GFR are autoregulated.

Renin-Angiotensin-Aldosterone System (RAAS)

Renin is the enzyme responsible for angiotensin II formation. It is synthesized, stored, and released by granular cells in the JGA region of the afferent arteriole. Renin release is stimulated by:

• Intrarenal baroreceptors: Renin secretion is inversely related to afferent arteriolar pressure.
• Macula densa: Increased NaCl delivery to the macula densa decreases renin secretion.
• Renal sympathetic nerves: Directly (β-receptor mediated) and indirectly cause increased renin secretion.
• Increased Angiotensin II levels decrease renin secretion (negative feedback).

The RAAS increases sodium and water reabsorption.

Aldosterone is the single most important controller of sodium reabsorption.

Atrial Natriuretic Peptide (ANP)

Activation of the ANP system decreases water and sodium reabsorption.

• Cells of the cardiac atria secrete ANP.
• Acts directly on collecting ducts to inhibit sodium reabsorption.
• Indirectly inhibits sodium reabsorption by inhibiting renin and aldosterone secretion.
• Vasodilates the afferent arteriole, increasing GFR and the filtered load of sodium (less time for reabsorption, thus increased excretion).