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Organic Anions and Transport in Kidneys

• Organic Anions: Substances such as bile salts, benzoylates, and subsilicylate fall under this category, primarily involved in renal handling. Known as organic anions, they are critical for various kidney functions.

• Transport Mechanism: Organic anions are taken up from the interstitial fluid into kidney cells lining the tubules and subsequently secreted into the tubular lumen for excretion in urine. This process largely utilizes an organic anion transporter.

• Examples of Organic Anions: Common examples include:

  • Bile salts

  • Aspirin

  • Artificial sweeteners (e.g., saffron)

  • Preservatives from sodas

• Transporter Function: The transporter utilizes alpha-ketoglutarate to create a gradient from dicarboxylates, facilitating the movement of organic anions into and out of cells.

Urea and Drug Transport

• Urea Removal: Urea is reabsorbed through passive diffusion, meaning it moves from areas of high concentration to low concentration.

• Penicillin Transport: Initially, penicillin was not synthesized; instead, probenecid was used to block its removal via the organic anion transporter. This ensured prolonged effects of penicillin by preventing it from being secreted out of the body.

Renal Filtration and Excretion

• Filtration Process: The kidneys filter out approximately 20% of the blood volume entering them. Out of this, about 70% is reabsorbed.

• Excretion Computation: The total amount excreted is determined by:

  • Filtration minus reabsorption plus secretion.

• Glomerular Filtration Rate (GFR): GFR is a critical measure of kidney function and can be calculated by evaluating the clearance of substances like creatinine.

GFR and Population Variability

• Measurement Parameters: GFR is assessed by measuring how much of a substance is being removed from the body (in mg/min) and its plasma concentration.

• Variation Among Populations: When assessing GFR across different populations, specifically Black Americans, it is essential to consider genetics related to muscle mass, leading to higher creatinine levels which may misrepresent kidney function if not accounted for.

Important Metrics for Kidney Function

• Clearance Measurement: Clearance is expressed in volume (mL/min) and is fundamental for understanding kidney functionality.

• Creatinine as a Benchmark: Creatinine clearance is often the standard for measuring GFR in clinical practices. Conditions like muscle mass variability can affect this measurement.

Renal Handling of Common Substances

• Key Substances:

  • Glucose: Ideally, 100% is reabsorbed back into circulation and remains unexcreted unless the transport mechanisms are overwhelmed (e.g., diabetes).

  • Inulin and PAH: Inulin is completely cleared and secreted, and PAH reflects similar parameters, evidencing the filtration efficacy of the kidneys.

  • Urea: Some is reabsorbed, indicating a balance required for proper nitrogen waste management within the body.

Micturition Process

• Urine Storage and Release: After flowing from the collecting ducts and into the bladder:

  • Sphincters Present: Internal (smooth muscle) and external (skeletal muscle).

  • Control Mechanism: Stretch receptors signal when to urinate, allowing reflexive micturition regulated by the autonomic nervous system.

Pathophysiology: Kidney Stones and Gout

• Kidney Stones: Resultant from urate crystals forming due to concentrated urine. It might lead to severe pain and complications depending on the location and size of the stones.

• Gout Mechanism: Uric acid accumulation due to metabolic issues can precipitate joint pain as crystals form; dietary factors like red meat increase uric acid levels, leading to symptoms.