General Principles of Renal Physiology

Kidney Functions

• Maintaining H2O balance in the body.
• Maintaining the proper osmolarity of body fluids.
• Regulating the quantity and concentration of most ECF ions, including Na^+, Cl^-, K^+, Ca^{+2}, H^+, HCO3^-, PO4, SO_4, and Mg^{+2}.
• Maintaining proper plasma volume, which is important in the long-term regulation of arterial blood pressure.
• Helping maintain the proper acid–base balance of the body by adjusting urinary output of H^+ and HCO_3^-.
• Excreting (eliminating) the end products of bodily metabolism such as urea, uric acid, and creatinine.
• Excreting many foreign compounds such as drugs, food additives, pesticides, and other exogenous non-nutritive materials that have entered the body.
• Producing erythropoietin, a hormone that stimulates red blood cell production.
• Producing renin, an enzymatic hormone that triggers a chain reaction important in salt conservation by the kidneys.
• Converting vitamin D into its active form.
• The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis.

Urinary System

• Consists of the urine-forming organs—the kidneys—and the structures that carry the urine from the kidneys to the outside for elimination from the body.
• Each kidney is supplied by a renal artery and a renal vein, which, respectively, enter and leave the kidney at the medial indentation.

Nephron

• Each kidney consists of about 1 million microscopic functional units known as nephrons.
• A nephron is the smallest unit capable of forming urine.
• Nephrons have two distinct regions:
  • An outer region called the renal cortex.
  • An inner region, the renal medulla, which is made up of striated triangles, the renal pyramids.

Urine Formation

• Three basic processes are involved in forming urine:
  • Glomerular filtration
  • Tubular reabsorption
  • Tubular secretion

Glomerular Filtration

• Normally, about 20% of the plasma that enters the glomerulus is filtered.
• This process, known as glomerular filtration, is the first step in urine formation.
• Three physical forces are involved in glomerular filtration:
  1. Glomerular capillary blood pressure, which is the fluid pressure exerted by the blood within the glomerular capillaries.
  2. Plasma-colloid osmotic pressure is caused by the unequal distribution of plasma proteins across the glomerular membrane.
  3. Bowman’s capsule hydrostatic pressure, the pressure exerted by the fluid in this initial part of the tubule, is estimated to be about 15 mm Hg.

GFR

• Normally, about 20% of the plasma that enters the glomerulus and glomerular filtration rate (GFR) is 125 ml/min.

Tubular Reabsorption

• As the filtrate flows through the tubules, substances of value to the body are returned to the peritubular capillary plasma.
• This selective movement of substances from inside the tubule (the tubular lumen) into the blood is called tubular reabsorption.
• Of the 180 liters of plasma filtered per day, 178.5 liters on average are reabsorbed.
• The remaining 1.5 liters left is eliminated as urine.

Proximal Tubule

• 65% of total filtrate is reabsorbed through the proximal tubule.
• Water, electrolytes (Na^+, K^+, Cl^- …).
• H^+, HCO_3^-.
• Glucose and amino acids (100% efficiency).
• Increased blood sugar due to diabetes causes increased glucose in urine (Glycosuria).

Descending Loop of Henle

• Only permeable to water!
• Result: Increased volume/osmolarity of filtrate.
• During reabsorption, H_2O passes through aquaporins, or water channels, formed by specific plasma membrane proteins in the tubular cells.
• Anti-diuretic hormone (ADH).

Ascending Loop of Henle

• Not permeable to water.
• 25% of ions (Na^+, Cl^-, K^+) reabsorbed through the ascending loop of Henle.

Hormonal Effect on Reabsorption

• Aldosterone
  • Affected region: Distal tubule, collecting duct.
  • Function: NaCl and water reabsorption, K secretion.
• Angiotensin II
  • Affected region: Proximal tubule.
  • Function: NaCl and water reabsorption, H secretion.
• ADH
  • Affected region: Distal tubule, collecting duct.
  • Function: H_2O reabsorption
• Atrial Natriuretic Peptide (ANP)
  • Affected region: Distal tubule, collecting duct.
  • Function: NaCl reabsorption
• The most important and best-known hormonal system involved in regulating Na is the renin-angiotensin-aldosterone system (RAAS).

Renin-Angiotensin-Aldosterone System (RAAS)

• The juxtaglomerular apparatus secretes a hormone, renin, into the blood in response to a fall in NaCl/ECF volume/blood pressure.
• Macula densa cells are renal sensor elements that detect changes in distal tubular fluid composition and transmit signals to the glomerular vascular elements.
• This tubuloglomerular feedback mechanism plays an important role in regulating glomerular filtration rate and blood flow.

Tubular Secretion

• The third renal process, tubular secretion, is the selective transfer of substances from the peritubular capillary blood into the tubular lumen.
• The most important substances secreted by the tubules are hydrogen ion (H^+), potassium (K^+), and organic anions and cations, many of which are compounds foreign to the body.
• Potassium secretion in the distal and collecting tubules is coupled to Na^+ reabsorption by the energy-dependent basolateral Na^+–K^+ pump.
• Potassium secretion is controlled by aldosterone.
• Aldosterone stimulates K^+ secretion by the tubular cells.
• A rise in plasma K^+ concentration directly stimulates the adrenal cortex to increase its output of aldosterone.
• Conversely, a decline in plasma K^+ concentration causes a reduction in aldosterone secretion and a corresponding decrease in aldosterone-stimulated renal K^+ secretion.

Plasma Clearance

• The plasma clearance of any substance is defined as the volume of plasma completely cleared of that substance by the kidneys per minute.