Renal System & Water Balance Notes

Functions of the Kidneys

• Regulation of fluid and electrolyte balance: Integrated with the cardiovascular system.

• Regulation of pH balance: Integrated with the respiratory system.

• Excretion of wastes.

• Production of hormones.

Key functional unit: The nephron, which performs:

• Filtration: Movement from blood to lumen.

• Reabsorption: From lumen to blood.

• Secretion: From blood to lumen.

• Excretion: From lumen to outside the body.

  • Approximately 20% of plasma passing through the glomerulus is filtered.

  • Less than 1% of filtered fluid is eventually excreted; >99% of plasma originally entering the kidney returns to systemic circulation.

  • >19% of fluid is reabsorbed.

The nephron consists of:

• Vascular elements: Afferent arteriole, glomerulus, efferent arteriole, peritubular capillaries, and vasa recta.

• Tubular elements: Bowman's capsule, proximal tubule, loop of Henle,distal tubule, and collecting duct.

Filtration and Autoregulation

• Net filtration pressure is determined by hydrostatic pressure ($P<em>H$), colloid osmotic pressure ($\pi$), and fluid pressure ($P</em>{fluid}$).

• Net filtration pressure = $P<em>H$ - $\pi$ - $P</em>{fluid}$ = 55 mm Hg - 30 mm Hg - 15 mm Hg = 10 mm Hg.

• Macula densa cells sense distal tubule flow and release paracrines affecting afferent arteriole diameter.

• Granular cells secrete renin, an enzyme involved in salt and water balance.

Principles Governing Reabsorption

• Epithelial/transcellular transport: Substances cross both apical and basolateral membranes of tubule epithelial cells to reach interstitial fluid.

• Paracellular pathway: Substances pass through cell-cell junctions between adjacent cells.

• The pathway taken depends on the permeability of epithelial junctions and the electrochemical gradient.

Proximal Na+ Reabsorption: A Direct Active Process

• Na+ enters the cell through various membrane proteins, moving down its electrochemical gradient.

• The Na+-K+-ATPase pumps Na+ out of the basolateral side of the cell.

Proximal Glucose Reabsorption: An Indirect Active Process

• Na+ moves down its electrochemical gradient, using the SGLT protein to pull glucose into the cell against its concentration gradient.

• Glucose diffuses out of the basolateral side of the cell using the GLUT protein.

• Na+ is pumped out by Na+-K+-ATPase.

Proximal Urea Reabsorption: A Passive Process

1. Urea has no active transporters in the proximal tubule; it moves by diffusion if there's a concentration gradient.

2. Initially, urea concentrations in the filtrate and extracellular fluid are equal.

3. Na+ and other solutes are reabsorbed, which makes the extracellular fluid more concentrated than the filtrate in the lumen.

4. Water moves by osmosis across the epithelium in response to the osmotic gradient.

5. Water reabsorption increases the urea concentration in the lumen.

6. Urea moves out of the lumen into the extracellular fluid through cells or the paracellular pathway once a concentration gradient exists.

Transport Saturation

• Transport rate is proportional to the plasma concentration of the substance until transporters are saturated.

• Once saturation occurs, transport rate reaches a maximum.

• The plasma concentration at which the transport maximum occurs is called the renal threshold.

Filtration, Reabsorption, and Excretion

• Filtration of glucose is proportional to the plasma concentration and does not saturate.

• Reabsorption of glucose is proportional to plasma concentration until the transport maximum ($T_m$) is reached.

• Glucose excretion is zero until the renal threshold is reached.

Driving Forces and Reabsorption

• In Bowman’s capsule, net driving pressure favors filtration.

• In the proximal tubule, lower hydrostatic pressure in the peritubular capillaries favors reabsorption of interstitial fluid.

Secretion

• Secretion involves the transfer of molecules from extracellular fluid into the lumen of the nephron.

• It is an active process important in homeostatic regulation (e.g., K+ and H+).

• Increasing secretion enhances excretion.

• It can be a competitive process (e.g., penicillin and probenecid).

Organic Anion Transporter (OAT) Example

1. Direct active transport: Na+-K+-ATPase keeps intracellular [Na+] low.

2. Secondary indirect active transport: Na+-dicarboxylate cotransporter (NaDC) concentrates a dicarboxylate inside the cell using the energy stored in the [Na+] gradient.

3. Tertiary indirect active transport: The basolateral organic anion transporter (OAT) concentrates organic anions (OA-) inside the cell, using the energy stored in the dicarboxylate gradient.

4. Organic anions (OA-) enter the lumen by facilitated diffusion.

Excretion and Clearance

• Excretion tells us what the body is eliminating but doesn't detail renal function.

• Excretion rate depends on the filtration rate of the substance and whether it is reabsorbed, secreted, or both.

• Renal handling of a substance and GFR are often of clinical interest.

• Clearance is the rate at which a solute disappears from the body by excretion or metabolism.

Useful Equations

• Excretion = Filtration – Reabsorption + Secretion

• Filtration (of X) = [X]plasma × GFR

• Clearance (of X) = Excretion rate (of X; mg/min) / [X]plasma (mg/ml plasma)

• When [X]plasma = renal threshold (of X), then reabsorption (of X) = Tm (for X)

Inulin Clearance

• If filtration and excretion are the same, there is no net reabsorption or secretion, and the clearance of a substance equals the GFR.

Glucose Clearance

• Normally, all glucose that filters is reabsorbed.

• With markedly increased plasma glucose, as seen in T1DM or T2DM, this might not occur.

Urea Clearance

• Urea clearance is an example of net reabsorption.

• If filtration is greater than excretion, there is net reabsorption.

• If clearance < GFR, net reabsorption.

Penicillin Clearance

• Penicillin clearance is an example of net secretion.

• If excretion is greater than filtration, there is net secretion.

• If clearance > GFR, net secretion.

Water Balance in the Body

• Water gain: Food and drink (2.2 L/day) + Metabolism (0.3 L/day) = 2.5 L/day.

• Water loss: Insensible water loss (0.9 L/day) + Urine (1.5 L/day) + Feces (0.1 L/day) = 2.5 L/day.

Kidney's Role in Water Balance

• Kidneys only conserve volume; volume loss can be replaced only by volume input from outside the body.

• GFR can be adjusted.

• If volume falls too low, GFR stops.

• Kidneys recycle body fluid.

• Body fluid volume can be offset by volume loss in the urine.

• Kidneys conserve volume through regulated H2O reabsorption.

Integrated Response to Changed Blood Volume/Pressure

• Decreased blood pressure/volume: Cardiovascular system increases cardiac output and vasoconstriction. Behavior: Thirst causes water intake. Kidneys conserve H2O to minimize further volume loss.

• Elevated blood pressure/volume: Cardiovascular system increases cardiac output and vasodilation. Kidneys excrete salts and H2O in urine.

Osmolarity Variations Along the Nephron

• Proximal tubule: 300 mOsM (isosmotic fluid leaving).

• Loop of Henle: 1200 mOsM.

• Distal tubule: 100 mOsM (ions reabsorbed, no water).

• Collecting duct: 50–1200 mOsM (variable reabsorption of water and solutes).

• Cortex is isosmotic to plasma; the renal medulla becomes progressively more concentrated.

Countercurrent Exchange

• Filtrate entering the descending limb becomes progressively more concentrated as it loses water.

• The ascending limb pumps out Na+, K+, and Cl–, and the filtrate becomes hyposmotic.

• Blood in the vasa recta removes water leaving the loop of Henle.

Making Dilute Urine

• H2O Impermeable Duct, Urine = 100 mOsM.

Vasopressin (ADH)

• Stimuli: Decreased blood pressure, decreased atrial stretch, osmolarity greater than 280 mOsM.

• Mechanism: Insertion of water pores (aquaporin-2) in the apical membrane of collecting duct epithelium.

• Result: Increased water reabsorption to conserve water.

Vasopressin Mechanism

1. Vasopressin binds to membrane receptor.

2. Receptor activates cAMP second messenger system.

3. Cell inserts AQP2 water pores into the apical membrane.

4. Water is absorbed by osmosis into the blood.

Making Concentrated Urine

• H2O Permeable Duct, Urine = 1200 mOsM

Responses to NaCl Ingestion

• Ingest salt (NaCl): No change in volume, osmolarity increases.

• Water intake: ECF volume and blood pressure increase.

• Kidneys: Conserve water but excrete salt and water (slow response).

• Cardiovascular reflexes: Lower blood pressure (rapid response).

• Outcome: Volume and blood pressure return to normal; osmolarity returns to normal.

Aldosterone

• Stimuli: Increased [K+], very high osmolarity, decreased blood pressure (RAS pathway).

• Acts on: P cells of the collecting duct.

• Effects: Increases Na+ reabsorption and K+ secretion.

Aldosterone Mechanism

1. Aldosterone combines with a cytoplasmic receptor.

2. Hormone-receptor complex initiates transcription in the nucleus.

3. Translation and protein synthesis makes new protein channels and pumps.

4. Aldosterone-induced proteins modulate existing channels and pumps.

RAAS (Renin-Angiotensin-Aldosterone System)

• Increased blood pressure, GFR, NaCl transport are direct effects.

• Macula densa of distal tubule communicates using paracrines.

• Sympathetic activity affects Granular cells of afferent arteriole produce Renin (enzyme).

• Angiotensinogen in the plasma constantly produces (from Liver) ANG I in plasma which creates ANG II in plasma (using ACE enzyme from the Blood vessel endothelium).

ANG II effects:

1. Increases vasopressin secretion

2. Stimulates thirst

3. Potent vasoconstrictor

4. Increases sympathetic output to heart and vessels

5. Increases Na+ reabsorption in proximal tubule

Natriuretic Peptides

• Increased blood volume causes increased atrial stretch.

• Myocardial cells stretch and release natriuretic peptides.

• Effects: Increased GFR, decreased renin and aldosterone, Na+ reabsorption, and sympathetic output; increased NaCl and H2O excretion.

Volume & Osmolarity Disturbances

• Osmolarity increases: Dehydration, Ingestion of hypertonic saline solution, eating salt without drinking water.

• Osmolarity decreases: Drinking large amounts of water, replacement of sweat loss with plain water.

• Volume increases: Ingestion of isotonic saline.

• Volume decreases: Hemorrhage, Dehydration.

Dehydration

• Decreased blood volume/blood pressure and increased osmolarity.

• Hypothalamic osmoreceptors, atrial volume receptors, carotid and aortic baroreceptors are stimulated.

• Cardiovascular, renal, Hypothalamic mechanisms activated.

pH Balance in the Body

• Plasma pH is maintained between 7.38-7.42 by:

  • Buffers (HCO3– in extracellular fluid, proteins in cells, phosphates in urine).

    • Renal and respiratory compensation.

Acid-Base Disturbances

• Acidosis: pH < 7.38

• Alkalosis: pH > 7.42

Reabsorption of HCO3- in the Proximal Tubule

1. NHE secretes H+.

2. H+ in filtrate combines with filtered HCO3– to form CO2.

3. CO2 diffuses into the cell.

4. CO2 combines with water to form H+ and HCO3–.

5. H+ is secreted again.

6. HCO3– is reabsorbed with Na+.

7. Glutamine is metabolized to ammonium ion and HCO3–.

8. Secreted H+ and NH4+ will be excreted.

Renal Handling of Acidosis

• Type A intercalated cells in the collecting duct function in acidosis.

• H+ is excreted; HCO3– and K+ are reabsorbed.

Renal Handling of Alkalosis

• Type B intercalated cells in the collecting duct function in alkalosis.

• HCO3– and K+ are excreted; H+ is reabsorbed.

Summary of Hormone Action on the Kidneys

• Vasopressin (ADH): Increases H2O permeability in the late distal tubule and collecting duct.

• Aldosterone: Increases Na+ reabsorption, K+ secretion, and H+ secretion in the distal tubule.

• Atrial natriuretic peptide (ANP): Increases GFR and decreases Na+ reabsorption.

• Angiotensin II: Increases Na+-H+ exchange and HCO3- reabsorption in the proximal tubule.