University Study Notes: Urine Formation and Renal Physiology

Summary of Steps in Urine Formation

Glomerular Filtration (Step 1): Blood enters the glomerulus, and a filtrate of small molecules passes through capillary pores into the tubule. This filtrate includes $H_2O$ , salts, glucose, amino acids, urea, uric acid, and some drugs.
Tubular Reabsorption (Step 2): Useful solutes are removed from the filtrate and returned to the blood. This includes $H_2O$ , salts, glucose, amino acids, and bicarbonate ( $HCO_3^-$ ).
Tubular Secretion (Step 3): Additional wastes are removed from the blood and added to the filtrate. These include $H^+$ , $NH_4^+$ , Urea, Uric acid, and creatinine.
Water Conservation (Step 4): This step removes $H_2O$ from the urine and returns it to the blood to concentrate wastes. It is primarily controlled by Antidiuretic Hormone (ADH).
Metabolic Wastes Clarified: * Urea: A waste product produced during the breakdown of amino acids in the liver (metabolism of proteins for energy). * Uric Acid: Produced from the breakdown of purines. A buildup of uric acid can lead to a condition known as gout. * Creatinine: Produced from the breakdown of creatine phosphate in muscle tissue. It is produced at a fairly constant rate and serves as an excellent marker of kidney health.

Glomerular Filtration (Step 1)

Blood Flow and Pressure: The kidneys receive approximately $15-25\%$ of cardiac output. Approximately $20\%$ of the blood plasma is filtered under pressure through capillary pores in the glomerulus into Bowman’s capsule.
Filtrate Composition: Small molecules that pass through the pores include $H_2O$ , salts, glucose, amino acids, urea, uric acid, and small proteins. Under normal conditions, blood cells should not pass through the glomerulus.
Glomerular Filtration Rate (GFR): This is the measurement of how much filtrate the kidney produces per minute. Higher GFR typically leads to higher urine output, while lower GFR leads to lower urine output.
Average GFR Values: * Males: $125\,ml/min$ or $180\,L/day$ . * Females: $105\,ml/min$ or $150\,L/day$ .

GFR as a Measurement of Kidney Function

Diagnostic Utility: GFR is considered the best measurement of kidney function and is used to determine the stage of kidney disease.
Stages of Kidney Function/Disease: * Normal: GFR > 90\,mL/min (Average range is $100-130\,mL/min$ ). * Mild Kidney Disease: $GFR$ between $60-89\,mL/min$ . * Moderate Kidney Disease: $GFR$ between $30-59\,mL/min$ . * Severe Kidney Disease: $GFR$ between $15-29\,mL/min$ . * Kidney Failure: GFR < 15\,mL/min.
Estimation (eGFR): GFR is typically estimated by determining blood levels of creatinine and Blood-Urea-Nitrogen (BUN).

Control of Glomerular Filtration Rate

Importance of Regulation: * If GFR is too high, needed substances are not reabsorbed quickly enough and are lost in the urine. * If GFR is too low, everything (including wastes) is reabsorbed.
Arteriole Dynamics: * Vasodilation of Afferent Arteriole: Increases GFR and increases urine output. * Vasoconstriction of Afferent Arteriole: Decreases GFR and decreases urine output.
Specific Modulators: * NSAIDS (e.g., ibuprofen, aspirin, Celebrex): These inhibit prostaglandins, leading to afferent vasoconstriction, decreased GFR, and decreased urine output. * Prostaglandins: Promote inflammation, clotting, pain, and fever; they cause afferent vasodilation which increases GFR and urine output. * Atrial Natriuretic Peptide (ANP): Triggers afferent vasodilation to increase GFR and urine output.
Exercise Effects: Strenuous exercise increases sympathetic activity and the release of catecholamines, leading to vasoconstriction of the afferent arteriole, reduced GFR, reduced blood flow to the kidneys, and decreased urine output.

Tubular Secretion and Reabsorption (Steps 2 and 3)

Definitions: * Tubular Secretion: Moving substances from the blood into the nephron tubule. * Tubular Reabsorption: Moving substances from the nephron tubule back into the blood.
Nephron Regulation Priorities: * Water balance. * Waste removal (urea, creatinine). * Electrolyte balance ( $Ca^{2+}$ , $Na^+$ , $K^+$ ), essential for nerve and muscle function. * Acid-Base balance ( $H^+$ and $HCO_3^-$ ). * Nutrient reclamation (glucose, amino acids, vitamins).
Site Activity: The Proximal Convoluted Tubule (PCT) is the part of the nephron most active in secretion and reabsorption.

ADH and Water Conservation

The ADH Mechanism: 1. Workouts/Sweating lead to hemoconcentration (concentrated blood plasma). 2. The Hypothalamus is stimulated, which in turn stimulates the posterior pituitary. 3. Antidiuretic Hormone (ADH) is secreted from the posterior pituitary. 4. ADH acts on the kidneys, specifically the collecting duct, to reabsorb more water. 5. Result: Increased plasma volume and decreased/concentrated urine output.
Osmolality: Refers to the amount of solute in a solution. High osmolality is concentrated; low osmolality is dilute.
Hydration Scenarios: * Normal Hydration: Normal ADH levels; collecting duct is moderately permeable to $H_2O$ ; urine output is normal ( $650\,mOsM/kg$ ). * Over-hydration: Blood concentration is low; ADH levels are LOW; collecting duct is NOT permeable to $H_2O$ ; water reabsorption is LOW; urine is dilute ( $400\,mOsM/kg$ ) and output increases. * Dehydration/Exercise/Sweating: Blood concentration is high; ADH levels are HIGH; collecting duct is MORE permeable to $H_2O$ ; water reabsorption is HIGH; urine is concentrated ( $1000\,mOsM/kg$ ) and output decreases.

Hormonal Regulation of Blood Pressure and Renal Function

High Urine Output: Leads to decreased blood volume and decreased blood pressure.
Renin-Angiotensin-Aldosterone System (RAAS): * Stimulus: Low Blood Pressure. * Pathway: Angiotensinogen (liver) $+$ Renin (kidneys) $\rightarrow$ Angiotensin I $+$ ACE (lungs) $\rightarrow$ Angiotensin II. * Angiotensin II Effects: Stimulates the adrenal glands to release Aldosterone (increases $Na^+$ and $H_2O$ retention) and the pituitary to release ADH (increases $H_2O$ retention). * Net Effect: Increased blood volume and increased blood pressure.
ANP and BNP: * Released by the heart in response to cardiac stretching/stress from high BP. * Mechanism: Causes afferent vasodilation and inhibits renin, aldosterone, and angiotensin II. * Net Effect: Increased GFR, increased urine output, decreased blood volume, and decreased blood pressure.

Renal Pathology

Renal Failure: Gradual loss of renal function, most commonly caused by Diabetes and Hypertension.
Signs/Symptoms: Increased BUN, increased Creatinine in blood, protein in urine, and decreased GFR.
Complications: * Acid-Base imbalance due to failure to secrete $H^+$ /reabsorb $HCO_3^-$ . * Fluid/Electrolyte imbalance. * Anemia. * Bone disease.
Azotemia: A serious condition where waste products normally found in urine build up in the body.
Dialysis Treatment: Uses a cellulose membrane with small pores. Dialysate solution contains essential ions ( $Na^+$ ) and glucose. Small waste molecules (urea, ions) pass into the dialysate, while large proteins and cells are maintained in the blood.

Questions & Discussion

Q: Patient has eGFR of $10\,mL/min$ ; what level is this? A: Kidney failure. Do you expect much urine output? No.
Q: Should blood cells pass through the glomerulus normally? A: No.
Q: In the nephron, is $H^+$ reabsorbed or secreted? A: $H^+$ is secreted and $HCO_3^-$ is reabsorbed.
Q: What is the relationship between GFR, urine output, and blood pressure? A: When GFR increases, urine output increases and blood pressure usually decreases.
Q: High blood urea/nitrogen and high creatinine usually indicate? A: Low eGFR and high renal failure.
Q: Effects of alcohol? A: Inhibits ADH, leading to HIGH urine output and LOW urine osmolality.
Q: Diabetes Insipidus results? A: High urine output, low blood volume, and decreased blood pressure.
Q: Diuretics effect? A: Decrease water reabsorption and increase urine output.