Kidney Functions and Regulation Quiz

Elimination via the Urinary System

• The urinary system consists of four parts: kidneys, ureters, bladder, and urethra
• Kidneys have two main functions:
  • Excretion of metabolic waste products from the blood
  • Regulation of water and ion content in the blood
• Kidneys filter blood, excreting dilute solutions (urine) containing urea, mineral ions, water, and xenobiotics.
• Kidneys have a large blood supply, ensuring waste materials do not build up. Blood circulates through the kidneys every 5 minutes.
• Kidneys play a major role in regulating blood volume by controlling water excretion and reabsorption.
• Renal damage can affect blood pressure regulation.
• Regulated electrolytes (Na+ and K+) by controlling secretion and reabsorption.
• Regulated pH of blood (acid-base balance) by controlling hydrogen ion secretion and reabsorption.

Kidney Nephron System

• Glomerular ultrafiltration: approximately 1/3 of blood plasma is filtered by the glomerulus, forming dilute urine (ultrafiltrate).
• Tubular secretion: Proximal Convoluted Tubule selectively secretes certain xenobiotics into urine.
• Tubular reabsorption: Distal Convoluted Tubule and Collecting Duct reabsorb many xenobiotics into blood passively.

Four Primary Mechanisms of Urinary Excretion

• 1. Filtration: Blood is filtered at the beginning of the renal tubule. The filtration membrane contains large pores so small molecules easily pass into the tubule. About 99% of the filtrate is reabsorbed into the blood, 1% is excreted as urine. Factors affecting filtration include molecule size and glomerular filtration as determined by blood flow and pressure.
• 2. Passive diffusion: Substances move across a biological membrane without energy (ATP). Simple diffusion, for small, uncharged, lipophilic molecules.
• 3. Active transport: Proteins (carrier proteins) are specific for certain weak acids/bases and transfer chemicals from blood to the tubular lumen. These systems may become saturated, limiting the amount of material excreted.
• 4. Facilitated diffusion: A process that resembles active transport but does not require energy.

Additional Factors Affecting Urinary Excretion

• Plasma protein binding: Highly bound compounds have decreased filtration ability, as are actively transported, but are not affected by protein binding.
• pH: The excretion of pH-dependent weak acids and bases is affected by pH changes.

Kidney and Liver Clearance

• Hydrostatic pressure pushes water and solutes out of the blood.
• Oncotic pressure opposes filtration due to plasma proteins.
• Filtration pressure is the net pressure favoring filtration.
• Substances like glucose, amino acids, sodium, chloride, and water are reabsorbed in the proximal tubule.
• The loop of Henle reabsorbs water in the descending limb and ions in the ascending limb.
• Ions (sodium, potassium, and water) are fine-tuned in the distal tubule and collecting duct, based on hormone regulation.

Low and High Log Kow Compounds

• Low Log Kow (hydrophilic): Highly water-soluble compounds tend to remain in the tubular lumen after filtration and are excreted in urine.
• High Log Kow (lipophilic): Highly lipophilic substances are efficiently reabsorbed by passive diffusion in the renal tubules and have low renal clearance. They may require hepatic metabolism for further clearance.

Failure of Homeostasis

• Kidney disease can occur caused by long-term diabetes, infections, and chemical poisoning.
• Bladder and kidney infections are caused by enteric bacteria entering the urethra.
• Kidney stones can form through crystallization of mineral salts and uric acid, blocking the passage of urine.

Kidneys and First-Pass Cardiac Output

• Kidneys receive approximately 25% of cardiac output due to their role in filtering blood and homeostasis.
• 20% is filtered through glomeruli (approximately 25g/day urea).
• Glomerular capillaries have large pores, allowing compounds up to 60 kDa (e.g., albumin) to be filtered.
• Tubular secretion actively transports acids, bases, and neutrals into renal tubules via organic cation transporters (OCT) and organic anion transporters (OAT).

Tubular Reabsorption and Secretion

• Tubular Reabsorption: Passive reabsorption depends on the ionization of xenobiotics. Lipophilic substances are absorbed more than hydrophilic substances. High urinary pH increases acid excretion, while low pH increases base excretion. Active transport via OCTs, peptide transporters (PEP), and MRPs (multidrug-resistant-associated proteins)
• Xenobiotic efflux pumps: Specialized proteins actively transport substances (particularly lipophilic compounds) across cell membranes. This is important for detoxification and/or drug resistance. Some belong to ATP-binding cassette (ABC) transporter superfamily - they hydrolyze ATP to power transport. P-gp (a major player in multidrug resistance).
• MRP1-7: Multidrug Resistance-Associated Proteins. Contribute to xenobiotic transport. Effective in handling organic anions and overlap in substrates with MDR/P-gp.
• OCT: Organic cation transporters; move quaternary ammonium ions, nicotine, cyperquat, dopamine, and MPP+. Other transporters may also move xenobiotics.
• OAT: Organic anion transporters move carboxylic acids, metabolites conjugated with glucuronide, glutathione, and sulfate (e.g., E2-SO42-).

Elimination of Xenobiotics

• Urine: filtration and excretion.
• Feces: via the GI tract or liver, involving metabolism and excretion.
• Expired air (in some cases): lungs, involving exhalation.
• Excretion in other secretions like breast milk, sweat, and saliva.
• Fecal elimination: a significant pathway for xenobiotic excretion.

Biliary Elimination

• Biliary elimination is an important pathway for xenobiotic and metabolite excretion.
• The liver removes xenobiotics from the blood via the portal circulation.
• The liver is the main site for xenobiotic biotransformation.
• The resulting metabolites (often more hydrophilic) can be directly excreted into the bile.
• Xenobiotics in food and water are carried to the liver via the hepatic portal vein and hepatic artery.
• Lipophilic compounds are filtered by the liver into hepatocytes; remaining lipophiles enter the systemic blood-flow via the hepatic vein.
• Hepatocytes secrete lipophiles into bile for biliary excretion, carrying these compounds to the gut.

Enterohepatic Cycle

• Enterohepatic circulation results in increased retention of xenobiotics if they are deconjugated by glucuronic acid in the intestines, then reabsorbed.
• Lipophiles are often difficult to excrete via the kidneys and liver. Persistence is measured by the elimination half-life (t1/2).
• Elimination half-life (t1/2) measures the rate of excretion from the body. First-order kinetics means the rate of elimination is proportional to the blood concentration of the xenobiotic. t1/2 is the time taken to eliminate one-half of remaining xenobiotic.
• Poor excretion of lipophiles can result in bioaccumulation in the body (i.e., body burden).
• Body burden is the concentration of a chemical in different tissues that cannot be directly sampled.

Persistent Organic Pollutants (POPs)

• Highly lipophilic organochlorine compounds, such as the Dirty Dozen, tend to remain in the body for a long time (persist).
• These chemicals are often bioaccumulative, meaning their concentration increases in the body over time.
• They are also toxic, potentially causing various health problems.
• Conjugation in the liver is very slow or non-existent for some POPs, which makes excretion through the bile difficult.

Test your knowledge on the vital roles of the kidneys within the urinary system. This quiz covers their functions such as blood pressure regulation, red blood cell production, and the role of nephron units. Dive into the complexities of kidney operations and their significance in maintaining homeostasis.