Kidney Function and the Nephron

Functional Units of the Kidney

The functional unit of the kidney is the nephron.
The urine formation process can be divided into three stages:
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion

Occurs in the glomerulus within Bowman's capsule.
High pressure in the glomerular capillaries pushes water and dissolved substances into the Bowman's capsule, forming the filtrate.
Blood vessels (capillaries) don't enter the nephron itself but are housed in Bowman's capsule.
Filtrate: Whatever is left in the nephron by the time it gets to the collecting duct becomes urine.
Normal capillary pressure vs Glomerulus capillary pressure.
- Normal capillaries pressure is around 25 mmHg
- Glomerulus capillaries pressure is around 65 mmHg, much higher than normal capillaries.
Not all solutes are filtered; some are too large (e.g., proteins, blood cells, platelets).
Average daily volume of glomerular filtrate:
- Females: 150 liters
- Males: 180 liters
Most of the filtrate (99%) is reabsorbed; only 1-2 liters are excreted as urine.

Substance	Present in Glomerulus	Enters Bowman's Capsule (Filtrate)
Water	Yes	Yes
Sodium Chloride	Yes	Yes
Glucose	Yes	Yes
Amino Acids	Yes	Yes
Hydrogen Ions	Yes	Yes
Protein	Yes	No (too large)
Erythrocytes	Yes	No (too large)
Platelets	Yes	No (too large)

Proteins and blood cells should not be present in urine; their presence indicates a disorder or inflammation.
Trace amounts of blood in urine may have external reasons, but not from the filtrate itself.

Most of the filtered water and many solutes are reabsorbed back into the bloodstream.
Occurs primarily in the proximal convoluted tubule (PCT).
Solutes are selectively reabsorbed by active and passive transport mechanisms.
Includes reabsorption of glucose, amino acids, urea, and various ions.
Reabsorption continues until the threshold level of a substance is reached; excess solutes are excreted.
Active Transport: Uses energy (e.g., ATP) to move substances against their concentration gradients.
Passive Transport: Moves substances down their concentration gradients without energy input.

Both active and passive transport mechanisms are at play.
All glucose, amino acids, and most mineral salts are actively transported back into the bloodstream (unless threshold is reached).
Most of the water is passively reabsorbed.
Most of the energy consumed by kidneys is used in the reabsorption of sodium ions, which is dissolved in the water component of the filtrate solution.
Sodium reabsorption is coupled with symporters (active transport) and antiporters (passive transport).
- Symporters: Reabsorption of sodium coupled with another substance (e.g., glucose).
- Antiporters: Passive transport where sodium and hydrogen ions switch places, important for maintaining pH.
Work of sodium ions transporters causes the concentration of other solutes to increase, leading to absorption through passage of diffusion.
Reabsorption of sodium ions and solutes promotes reabsorption of water via osmosis.

Remaining water, salts, and urea pass from PCT into the descending limb, then along the loop, and up the ascending limb.
Descending limb is permeable to water (has aquaporins) but less permeable to solutes.
- Water moves from the descending limb into the interstitium.
Ascending limb is impermeable to water but permeable to sodium, chlorine, and somewhat to urea.
- Solutes diffuse from the ascending limb into the interstitium.
The concentration of fluid inside the renal tubules is highest at the deepest part of the renal medulla and is less concentrated in the renal cortex, creating a concentration gradient.
Thin ascending limb differs from the descending limb and that it is impermeable to water, but highly permeable to sodium and chlorine and somewhat permeable to urea.
The thick ascending limb reabsorbs NaCl via active transport.

Water, urea, and salts pass from the ascending limb of Henle to the DCT.
DCT is responsive to antidiuretic hormone (ADH), which controls water reabsorption.
The more ADH present, the more water is reabsorbed.

Transfer of materials from the blood into the nephron to be excreted.
Substances such as hydrogen ions (H+), potassium ions (K+), ammonia, and drugs are secreted.
Two main outcomes:
- Secretion of hydrogen ions helps control blood pH.
- Secretion of other substances helps eliminate them from the body.

Glomerulus to Bowman's Capsule: Filtrate formed due to high pressure.
PCT: Active and passive transport of glucose, amino acids, water, and ions.
Loop of Henle:
- Descending Limb: Free movement of water through aquaporins.
- Loop and Thin Ascending Limb: Passive transport of NaCl.
- Thick Ascending Limb: Active transport of NaCl.
DCT: Active and passive transport, hormonal control (ADH).
Collecting Duct: Final adjustments made before excretion.

Glucose is filtered from the glomerulus into Bowman's capsule.
Normally, all glucose is reabsorbed.
If blood glucose concentration is too high (e.g., diabetes), the nephron becomes saturated and cannot reabsorb all the glucose.
Glucose remains in the urine (glucosuria).
Rarely, it may be due to a genetic disorder affecting active transport.

Hormones regulate water reabsorption to maintain homeostasis.
Two main systems:
- ADH (Antidiuretic Hormone)
- Renin-Angiotensin-Aldosterone System (RAAS)

Regulates water balance by increasing water reabsorption in the kidneys.
Released when water is lost (e.g., dehydration, sweating).
Osmoreceptors in the hypothalamus detect changes in osmotic pressure.
Increased osmotic pressure causes water to leave cells, shrinking hypothalamic cells.
Shrunken cells signal the pituitary gland to release ADH.
ADH causes kidneys to retain water.
Thirst sensation is caused by the shrinking of hypothalamic cells.
Negative feedback loop:
- Stimulus disrupts homeostasis.
- Osmolarity of plasma and interstitial fluid increases.
- Receptors in hypothalamus send nerve impulse to pituitary to release ADH.
- Nephron becomes more permeable to water, retaining water.
85% of water is reabsorbed by the PCT, while the remaining 15% is controlled by ADH.

Regulates blood volume and pressure.
Decreased blood volume or pressure causes less stretch on the afferent arteriole walls.
Cells near the afferent arteriole secrete renin into the blood.
Renin converts angiotensinogen into angiotensin.
Angiotensin decreases glomerular filtration rate and stimulates aldosterone release from the adrenal cortex.
Aldosterone increases NaCl and water reabsorption.
Angiotensin also stimulates ADH secretion.
All these mechanisms cause an increase in blood volume and pressure.

Substances that slow renal reabsorption of water, causing increased urine flow (diuresis).
Natural diuretics: alcohol, coffee, tea.
Inhibit ADH secretion, leading to increased water excretion.

Maintaining pH balance is crucial for protein structure and function.
Healthy blood pH range: a very small range around 7.35-7.45.
Metabolism produces hydrogen ions, which can cause blood pH to drop.
Sources of hydrogen ions: protein breakdown, anaerobic respiration, fat metabolism, carbon dioxide transport, etc.
Buffer systems regulate pH by binding or releasing hydrogen ions.
The most common buffer system is the carbonic acid-bicarbonate buffer system, which can attach to or release hydrogen ions.
Hydrogen ions bound to buffers are excreted in urine.
Nephrons also reabsorb to maintain pH balance.