Physiology of Osmolality and Renal Function

Kidney Function and Nephron Structure

• A nephron is the functional unit of the kidney.
• Each kidney contains approximately one million nephrons.
• Blood enters the glomerulus where some fluid and dissolved substances are absorbed into the tubule.
• The fluid and substances needed by the body are returned to the blood through vessels alongside the tubule.
• Waste materials are passed to the bladder by the tubule.

Renal Function Testing and Non-protein Nitrogen Substances

• The objective of renal function tests are to define terminologies related to renal function testing, define non-protein nitrogenous compounds (NPN), and discuss about NPN compounds.
• NPN compounds include urea, creatinine, uric acid, creatinine clearance, and electrolytes.

Renal System Introduction

• Definitions of important concepts in anatomy and functions of the renal system.
• The key elements to understand and define renal threshold and Non-protein nitrogenous (NPN) compounds.

Urea and BUN Concepts

• Non-protein nitrogenous (NPN) substances are metabolic end products that contain nitrogen but are not proteins.
• Azotemia is an excess of urea or other nitrogenous compounds in the blood.
• Antidiuretic hormone (ADH) is a posterior pituitary gland hormone. It plays an important role in reabsorption of water in the kidneys.
• Diabetic insipidus is a disorder associated with the secretion/metabolism of ADH, characterized by excessive urine production.

Urea, BUN, and Clinical Significance

• Urea is synthesized in the liver from ammonia.
• The rate of incidence of urea cycle disorders is about 1 in 2500.
• Common symptoms of urea cycle defects include vomiting, irritability, lethargy, seizures, mental retardation, coma, and early death.
• Urea is primarily formed and transported to the kidneys through the body's circulatory system.

Creatinine and Metabolism

• Creatinine is formed from creatine in muscles and spontaneously derived from these muscles.
• Creatinine production occurs continuously at a nearly constant rate each day.
• Creatinine is primarily excreted from the body via glomerular filtration and mostly not reabsorbed or secreted by the tubules within the kidneys.

Creatinine Clearance (CrCl)

• A creatinine clearance test measures the volume of blood cleared of the substance, creatinine per minute.
• A good test for GFR.
• The amount of creatinine produced each day is constant and is proportional to muscle mass.
• Patients should be well hydrated and avoid caffeine (coffee and tea) on the day of the test.
• The test involves collecting 24-hour urine samples and obtaining a serum/plasma creatinine sample sometime during the collection period.
• The standard clearance formula is UV/P (urine creatinine / plasma creatinine).
• Clearance can be corrected by multiplying by constant 1.73/body surface area (BSA)
• Estimated GFR (eGFR) is calculated each time serum creatinine is reported.
• EGrF does not require collecting timed urine.

Uric Acid Information

• Uric acid is primarily an end product of purine catabolism in humans, formed in the liver.
• Uric acid is transported in the plasma from the liver to the kidney, where it is filtered by the glomerulus.
• Most of uric acid is reabsorbed then reused in the proximal tubules.
• Renal excretion accounts for approximately 70% of uric acid elimination; the remainder is degraded by bacterial enzymes within the gastrointestinal tract.

Uric Acid Clinical Application

• Uric acid levels are used to assess inherited disorders of purine metabolism.
• Uric acid levels are used to confirm diagnosis and monitor gout treatment.
• Uric acid levels are used to assist in the diagnosis of renal calculi.
• Uric acid levels are measured to prevent uric acid nephropathy during chemotherapy.
• Uric acid levels are used to detect kidney dysfunction.

Normal Values for Uric Acid

• Normal values of uric acid for males are generally 3.4-7 mg/dL and 2.5-6 mg/dL are considered normal for females

Gout and Hyperuricemia

• Gout is a disease characterized by pain and inflammation in the joints caused by precipitation of sodium urates.
• Gout is primarily diagnosed in men between 30 and 50 years of age.
• Patients with Gout are susceptible to renal calculi (kidney stones).
  • The factors associated with the increased metabolism of cell nuclei include chemotherapy in leukemia, lymphoma, and multiple myeloma patients.

Urea and other substances (e.g., electrolytes)

• Electrolytes are substances whose molecules dissociate into ions when dissolved in water.
• The kidneys regulate the internal chemical environment of the body through conservation or excretion processes.
• The normal values for many key electrolytes are detailed in a table as part of the overall study guide.
• A variety of electrolyte dysfunctions can occur.
• Detailed notes on each of the major electrolytes are described in the accompanying study guide.