Urinary System Part 2: Renal Physiology

Urinary System Part 2: Renal Physiology

• The urinary system maintains homeostasis by regulating blood volume and composition.
• Urine is concentrated to 855-1355 mOsm/L.
• The system excretes solutes, mainly metabolic wastes.

Renal Physiology: Normal Laboratory Values

• Ions (mEq/L):
  • Sodium (Na+): 135-145 in plasma, 40-220 in urine
  • Potassium (K+): 3.5-5.0 in plasma, 25-100 in urine
  • Bicarbonate (HCO3-): 20-28 in plasma, 1.9 in urine
• Metabolites and Nutrients (mg/dL):
  • Glucose: 70-110 in plasma, 0.009 in urine
  • Lipids: 450-1000 in plasma, 0.002 in urine
  • Proteins: 6.0-8.0 g/dL in plasma, 0.000 in urine
• Nitrogenous Wastes (mg/dL):
  • Urea: 8-25 in plasma, 1800 in urine
  • Creatinine: 0.6-1.5 in plasma, 150 in urine
  • Uric acid: 2-6 in plasma, 40 in urine
  • Ammonia: <0.1 in plasma, 60 in urine

Renal Physiology: Metabolic Wastes

• Urea: The most abundant organic waste, a byproduct of amino acid breakdown.
• Creatinine: A byproduct of creatine phosphate breakdown in muscles.
• Uric acid: Formed during the recycling of RNA's nitrogenous bases.

Renal Physiology: Urine Formation

• There are three processes involved in urine formation:
  • Filtration: Blood hydrostatic pressure forces water and solutes across glomerular capillaries into the capsular space.
  • Reabsorption: Water, ions, and other substances are reabsorbed from renal tubules into peritubular capillaries.
  • Secretion: Substances like wastes, drugs, and excess ions are secreted from peritubular capillaries into renal tubules.

Glomerular Filtration

• Filtration: Blood hydrostatic pressure forces water and solutes through the glomerular capillaries into the capsular space.

• Filtration membrane:

  • Fenestrations of endothelial cells allow small molecules to pass through.
  • Basement membrane (collagen fibers and proteoglycans; large negatively charged proteins cannot fit).
  • Filtration slits between podocytes, regulating the size of substances passing through

• Net Filtration Pressure (NFP): The driving force for filtration determined by:

  • Glomerular blood hydrostatic pressure (GBHP) - opposing: Capsular hydrostatic pressure (CHP) and Blood colloid osmotic pressure (BCOP)
  • Calculating NFP: GBHP - CHP - BCOP = 10mmHg (under normal circumstances)

• Normal filtration fraction (FF) = 16-20%.

• Daily glomerular filtrate = 150L-180L.

• 99% of filtrate reabsorbed back into the blood

• Glomerular Filtration Rate (GFR)

  • Amount of filtrate formed per minute in both kidneys (normal 105-120 ml/min)
  • Directly related to NFP; eGFR used to test kidney function

• The body carefully monitors GFR to maintain homeostasis.

• High GFR: Needed substances pass too quickly through the renal tubules, and are lost in urine

• Low GFR: Metabolic wastes are not filtered from the blood into the renal tubules.

Renal Autoregulation

• Mesangial cells: Located between adjacent glomerular capillaries. They control capillary diameter and filtration rate.
• Juxtaglomerular apparatus (JGA): Includes specialized cells in the distal tubules and glomerular arterioles that regulate blood pressure and filtration rate.
  • Macula densa cells detect changes in tubule NaCl concentration.
  • Juxtaglomerular cells (granular cells) secrete renin in response to low blood pressure.
• Two types of myogenic mechanism:
  • Myogenic: Stretch receptors in afferent arterioles respond to increased or decreased blood pressure.
  • Tubuloglomerular feedback: Macula densa cells detect changes in tubular Na+ and Cl− concentrations, which affects renin release
• GFR can be regulated by nervous and hormonal systems

Hormonal Regulation:

• Angiotensin II: Part of the Renin-Angiotensin-Aldosterone System (RAAS). Aldosterone causes more Na+, Cl- and H2O reabsorption.
• Antidiuretic hormone (ADH): Responds to low blood volume or high blood osmolarity; principal cells increase aquaporin numbers to reabsorb more water.
• Atrial natriuretic peptide (ANP): Responds to increased blood pressure; inhibits Na+ reabsorption and lowers blood pressure

Reabsorption & Secretion (Proximal Convoluted Tubule/PCT):

• PCT: The most important site of reabsorption.
  • Active transport: 100% of glucose, amino acids, HPO42-, SO42-, and lactic acid, and 85-90% of filtered bicarbonate
  • Passive transport: 65% of filtered water, 65% of filtered sodium, potassium, 50% of filtered chloride, urea
• PCT: Secretion
  • Active transport: elimination of H+ (blood pH regulator) and other substances e.g. NH4+ and medications
• Overview:
  • Reabsorption: 100% Glucose, amino acids, phosphate, lactate
  • Reabsorption: 85-90% bicarbonate
  • Secretion: NH4+, drugs

Reabsorption & Secretion (Nephron Loop):

• Reabsorption: (descending limb/ascending limb):
  • Some water, 20-30% salt, 35% chloride, and variable amounts of Mg2+, C2+, and bicarbonate in loop of Henle.
• 15% of filtered water reabsorbed only in the descending limb.
• Lots of reabsorption. Very little secretion.

Reabsorption & Secretion (Early Distal Convoluted Tubule):

• Reabsorption:
  • 10-15% water; mostly passive
  • 5% of Na+ and Cl- (active transport)
  • PTH acts to reabsorb calcium

Reabsorption & Secretion (Late Distal Convoluted Tubule and Collecting Duct):

• Reabsorption:
  • Principal cells: Reabsorb Na+ and H2O; controlled by ADH and aldosterone.
  • Intercalated cells: Reabsorb K+ and HCO3-; regulate pH.
• Secretion:
  • Principal cells: Secrete K+
  • Intercalated cells: Secrete H+
  • Urea:
• 90-95% of remaining filtered solutes and water reabsorbed or secreted based on body needs

Hormonal Regulation of Tubular Reabsorption:

• Many hormones play a role:
  • Renin-Aldosterone-Angiotensin System (RAAS)
  • Antidiuretic hormone (ADH)
  • Atrial natriuretic peptide (ANP)
  • Parathyroid hormone (PTH)
  • Calcitonin

Diabetes Insipidus (DI):

• Definition: Inadequate response to or production of ADH
  • Types:
    • Central DI: Posterior pituitary or hypothalamus defect impacting ADH production or release.
    • Nephrogenic DI: Kidneys are resistant to ADH.
  • Symptoms: Excessive excretion of dilute urine, dehydration, thirst, fatigue.
  • Treatment: - Desmopressin (synthetic ADH) for Central DI or
    • Thiazides for Nephrogenic DI