PPBM1321 Functions of Kidney PDF

PPBM1321: Functions of Kidney & Concept of Renal Clearance Dr. Rosazra Roslan 30/12/2024 Learning Objectives 1. Describe the primary functions of the kidney. 2. List the vascular and tubular components of the nephron and describe their functions. 3. Explain the three basic renal...

PPBM1321: Functions of Kidney & Concept of Renal Clearance Dr. Rosazra Roslan 30/12/2024 Learning Objectives 1. Describe the primary functions of the kidney. 2. List the vascular and tubular components of the nephron and describe their functions. 3. Explain the three basic renal processes. 4. Define renal clearance and discuss its significance in assessing kidney function and the excretion of various substances. Functions of Kidney Introduction Kidneys are organs specialized to filter the blood – important contribution to the removal of metabolic waste products as well as to the maintenance of fluid and electrolyte balance Functions of kidneys: 1. Regulatory functions 2. Excretory functions 3. Secretory/endocrine functions Specific Functions of the Kidneys Regulation of extracellular fluid volume and osmolarity. Regulation of inorganic electrolyte concentrations (e.g., sodium, potassium, calcium). Removal of metabolic waste products such as urea, uric acid, creatinine, and urobilinogen. Excretion of foreign compounds (e.g., drugs, pesticides, food additives). Maintenance of acid-base balance in conjunction with the respiratory system. Production of hormones (e.g., erythropoietin) and enzymes (e.g., renin). Regulation of Extracellular Fluid Volume The regulation of extracellular fluid volume, in particular, plasma volume, is important in the long- term regulation of blood pressure:  An increase in plasma volume  an increase in blood pressure  A decrease in plasma volume  a decrease in blood pressure Plasma volume is regulated primarily by altering the excretion of sodium in the urine Other inorganic electrolytes regulated by the kidneys include chloride, potassium, calcium, magnesium, sulfate, and phosphate. Osmolarity Regulation Plasma osmolarity is maintained around 290 mOsm to prevent cellular dehydration or swelling:  An increase in plasma osmolarity causes water to leave the cells  Cellular dehydration  A decrease in plasma osmolarity causes water to enter the cells  Cellular swelling and possibly lysis Plasma osmolarity is regulated primarily by altering the excretion of water in the urine Metabolic Waste Removal Nitrogenous wastes like urea (from amino acids) and uric acid (from nucleic acids) are excreted. Creatinine (from muscle metabolism) and urobilinogen (from haemoglobin metabolism) are eliminated. Excretion of Foreign Compounds The kidneys remove drugs (e.g., penicillin), non- nutritive substances (e.g., saccharin), and pesticides. Accumulation of these substances can be toxic. Acid-Base Balance Maintenance The kidneys excrete hydrogen ions (H⁺) and conserve bicarbonate (HCO₃⁻) when extracellular fluid is acidic. Conversely, they conserve H⁺ and excrete HCO₃⁻ when extracellular fluid is alkaline. Normal arterial blood pH is maintained at 7.4. Hormone and Enzyme Production Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin: Stimulates red blood cell production in response to renal hypoxia; deficiency leads to anemia in chronic renal disease. Renin: Involved in the renin-angiotensin-aldosterone system for plasma volume and blood pressure regulation. Vitamin D Activation: Renal enzymes convert vitamin D into its active form, 1,25-dihydroxyvitamin D3 (calcitriol), essential for calcium balance. Functiona l Anatomy of Kidneys Functional Anatomy The kidneys are located in the posterior abdominal wall, outside the peritoneal cavity, on either side of the vertebral column, slightly above the waistline. Each kidney measures approximately 11 cm in length, 6 cm in width, and 3 cm in thickness in an adult. The kidney is divided into two main regions:  Outer renal cortex  Inner renal medulla Functional Anatomy (cont.) Each kidney contains over 1 million nephrons, the functional units responsible for filtration and urine formation. The nephron has two main components: 1. Vascular component: Includes blood vessels that supply and drain the nephron. 2. Tubular component: Involved in the filtration, reabsorption, and secretion processes. 1. Vascular Component Filtration occurs in the glomerular capillaries located in the kidney's cortical region. Water and solutes exit the vascular compartment through the glomerular capillaries and enter the tubular component of the nephron for processing. Blood enters the glomerulus via the afferent arterioles. After filtration, the glomerular capillaries merge into the efferent arterioles, which carry unfiltered plasma and blood cells. 1. Vascular Component (cont.) The efferent arterioles branch into peritubular capillaries, which:  Provide nourishment to renal tissues.  Facilitate the return of reabsorbed substances from the tubular component to the vascular compartment. These capillaries are closely associated with the renal tubules, wrapping around them to enable efficient exchange. Peritubular capillaries converge to form venules and larger veins, which remove blood from the kidneys. 2. Tubular Component The kidneys process approximately 180 litres of filtrate daily. About 99% of the filtrate is reabsorbed into the vascular compartment, depending on fluid intake. Tubule reabsorption is facilitated by its structure, which consists of a single layer of epithelial cells.  2. Tubular Component (cont.) Filtrate leaves the glomerular capillaries and enters Bowman’s capsule. The filtrate then passes through these tubular segments:  Proximal convoluted tubule (in the cortex).  Loop of Henle (in the medulla, with descending and ascending limbs).  Distal convoluted tubule (in the cortex).  Collecting duct (descends through the medulla). Filtrate remaining at the end of the collecting duct drains into the renal pelvis, then to the ureters, and is excreted as urine. Types of Nephrons Cortical Nephrons:  Glomeruli are located in the outer cortex.  Loops of Henle are short and do not penetrate deeply into the medulla.  Constitute 70%–80% of nephrons in humans. Juxtamedullary Nephrons:  Glomeruli are located in the inner cortex, near the medulla.  Loops of Henle are long, extending deep into the medulla.  Associated with specialized vasa recta capillaries that run parallel to the Loops of Henle and collecting ducts.  Constitute 20%–30% of nephrons in humans. Basic Renal Processes Introduction The nephron performs three basic processes: 1. Filtration: Removes fluid and solutes from plasma into the nephron. 2. Reabsorption: Returns essential substances and water to the bloodstream. 3. Secretion: Removes additional substances from the blood into the nephron for excretion.  Filtration Occurs in the glomerulus and Bowman’s capsule. Involves the movement of fluid and solutes from the glomerular capillaries into Bowman’s capsule. Non-selective process:  Everything in plasma except plasma proteins is filtered. Approximately 20% of plasma is filtered as it passes through the glomerulus. Results in an average glomerular filtration rate (GFR) of:  125 mL/min or 180 L/day of filtrate.  Reabsorption Movement of filtered substances from the renal tubule into the peritubular capillaries for return to the bloodstream. Occurs throughout the renal tubule. Approximately 178.5 L/day of filtrate is reabsorbed (99%). Results in an average urine output of 1.5 L/day (1%). Secretion Movement of selected unfiltered substances from the peritubular capillaries into the renal tubule. Substances that are filtered or secreted, but not reabsorbed, are excreted in the urine. Concept of Renal/Plas ma Clearance Introduction Plasma clearance indicates the kidneys’ effectiveness in removing the substances. Uses of renal clearance:  Assessing kidney function: Determines how well the kidneys are filtering and processing substances. An assessment of kidney function is important to:  Identify renal impairment  Monitor disease progress  Assess baseline measurements before starting treatment with certain drugs Plasma Clearance Plasma clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time (measured in mL/min). It measures the efficiency of the kidneys in removing substances from the blood. Plasma clearance calculations are used to determine:  Glomerular Filtration Rate (GFR): The volume of plasma filtered by the kidneys per minute.  Effective Renal Plasma Flow (ERPF): The plasma volume effectively perfused through the kidneys. To calculate plasma clearance, the following must be measured:  Rate of urine formation (V): Measured in mL/min.  Concentration of the substance in the urine (U): Measured in mg/mL.  Concentration of the substance in the arterial plasma (P): Measured in mg/mL. 1. Plasma Clearance to Determine GFR The plasma clearance of a substance is calculated as follows: To use the plasma clearance of a substance to determine GFR, several criteria regarding the substance must be met.  Be freely filtered at the glomerulus.  Not be reabsorbed by the renal tubules.  Not be secreted into the tubules.  Not be synthesized or broken down by the tubules.  Not alter the GFR. 1. Plasma Clearance to Determine GFR A substance that fulfils these criteria is inulin, a polysaccharide found in plants.  Administered intravenously at a constant plasma concentration for at least 1 hour.  Urine is collected to measure: Volume of urine produced. Concentration of inulin in urine. Concentration of inulin in plasma. Example Calculation of Plasma Clearance Using Inulin Data:  Urine volume: 60 mL/hour (1 mL/min).  Urine inulin concentration: 20 mg/mL.  Plasma inulin concentration: 0.16 mg/mL. Since inulin is neither reabsorbed nor secreted, plasma clearance of inulin equals GFR. Measurement is accurate but inconvenient, requiring continuous infusion of inulin for hours. Creatinine as a Practical Alternative for Estimating GFR Creatinine is an end-product of muscle metabolism released into the blood at a steady rate. Measurement involves:  A single blood sample.  A 24-hour urine collection. Plasma clearance of creatinine provides an estimate of GFR, but:  Slightly overestimates GFR (by ~10%) due to minor secretion of creatinine into urine. Factors Affecting Renal Clearance Filtration at the glomerulus: Determines how much of the substance enters the renal tubules. Reabsorption: Decreases the amount of the substance excreted in urine. Secretion: Increases the amount of the substance excreted in urine. 2. Plasma Clearance to Determine ERPF The substance must:  Be freely filtered at the glomerulus.  Not be reabsorbed by the tubules.  Be secreted into the tubules. A substance that fulfills these criteria is para-aminohippuric acid (PAH):  Filtered at the glomerulus.  Secreted by the proximal tubules if not filtered. Result: All plasma flowing through nephrons is cleared of PAH. ERPF is approximately 625 mL/min. Plasma Clearance (cont.) The plasma clearance rate varies for different substances depending on how the kidneys handle each substance. If a substance is filtered and reabsorbed but not secreted, then its plasma clearance rate is always less than the GFR. A substance that is partially reabsorbed, such as urea, only part of the filtered plasma is cleared of urea each minute and its plasma clearance rate is less than the GFR. On the other hand, if a substance is filtered and secreted but not reabsorbed, its plasma clearance rate is always greater than the GFR. Filtration Fraction Definition: The percentage of plasma flowing through the nephrons that is filtered into the tubules. Formula: On average, 20% of plasma flowing through the glomerulus is filtered into the tubules.