Block: URIN 313 Physiology of THE URINARY SYSTEM Lecture 5

1. Block: URIN 313Physiology of THE URINARY SYSTEM Lecture 5 • Dr. AmelEassawi • Dr. ShaikhMujeeb Ahmed

2. Tubular Secretion

3. Define tubular secretion. • Understand the normal distribution of body potassium. • Role of tubular secretion in maintaining K+ concentration. • Mechanisms of tubular secretion. • Understand the relationship between plasma potassium and aldosterone. • Understand the influence of acid-base status on the regulation of potassium excretion. OBJECTIVES

4. Tubular Secretion is transfer of substances from the peritubular capillaries into the tubular lumen. • Tubular secretion is important for: • Disposing of substances not already in the filtrate. • Eliminating undesirable substances such as urea and uric acid. • Getting rid of excess potassium ions. • Controlling blood pH by secreting H+. Tubular Secretion

5. Tubular Secretion

6. First step is simple diffusion from peritubular capillaries to interstitial fluid. • Entry from interstitial fluid to tubular cell can be active or passive. • Exit from tubular cell to lumen can be active or passive. • The most important substances secreted by the tubules: - Hydrogen ion - Potassium ion - Para Amino Hippuric acid ( PAH) - Organic anion and cations - Drugs e.g. penicillin, aspirin, Cemitidine - Hormones e.g. erythropoietin, renin Tubular Secretion

7. Important in acid–base balance. • Hydrogen ion can be secreted by proximal, distal, and collecting tubules, • depending on the acidity of the body fluids. • When the body fluids are too acidic, H+ secretion increases. • Conversely, H+ secretion is reduced when the H+ concentration in the body fluids is too low. Hydrogen ion secretion

8. Potassium ion secretion In the principal cells of the distal and collecting tubules is coupled to Na+reabsorption by the energy-dependent basolateral Na+–K+ pump MECHANISM OF K+ SECRETION

9. Controlled by aldosterone. • Potassium is one of the most abundant cations in the body • about 98% of the K+ is in the ICF, because the Na+ –K + pump actively transports K+ into the cells. • Because only a relatively small amount of K+ is in the ECF, even slight changes in the ECF K+ load can have a pronounced effect on the plasma K+ • concentration. • Changes in the plasma K+ concentration have a marked influence on membrane excitability. Therefore, plasma K+ concentrations are tightly controlled, primarily by the kidneys. • Actively reabsorbed in the proximal tubule and actively secreted by principal cells in the distal and collecting tubules. • One type of intercalated cell actively secretes K+ and another type actively reabsorbs K+ in the distal and collecting tubules in conjunction with H+ transport. Potassium ion secretion

10. Early in the tubule K+ is reabsorbed in a constant, unregulated fashion, whereas K+ secretion later in the tubule by the principal cells is variable and subject to regulation. • During K+ depletion, K+ secretion is reduced to a minimum • Conversely, when plasma K levels are elevated, K+ secretion is increased to reduce the plasma K+ concentration to normal. • Thus, K+ secretion, not the filtration or reabsorption of K+, is varied in a controlled fashion to regulate the rate of K+ excretion and maintain the desired plasma K+ concentration. Potassium ion secretion

11. Potassium ion secretion

12. Potassium ion secretion

13. Several factors can alter the rate of K+ secretion, the most important being aldosterone. • Aldosterone causes Na+reabsorption and K+ secretion by principal cells. • Increased K+ concentration directly stimulates the adrenal cortex to increase aldosterone secretion. • Decreased K+ concentration in plasma – causes decreased aldosterone secretion. • Effect of H+ secretion on K+ secretion • An increased rate of secretion of either K+ or H+ is accompanied by a decreased rate of secretion of the other ion. Normally the kidneys secrete a preponderance of K+, but when the body fluids are too acidic and H+ secretion is increased as a compensatory measure, K+ secretion is correspondingly reduced. Potassium ion secretion

14. K+ plays important role in membrane potential. • K+ changes in ECF, when there is increase or decrease in K+ level, it can affect the heart and can cause decreased cardiac excitability, decrease conduction, cardiac arrhythmia, fibrillation. • K+ changes not only affects cardiac muscle but it also affects skeletal muscle and nerve conduction. • Decreased K+ causes hyperpolarization, which decreases the excitability of the nerve. • In Skeletal muscle, K+ depletion causes muscle weakness • K+ depletion causes abdominal distension due to smooth muscle dysfunction. Potassium ion secretion

15. Potassium ion secretion

16. Potassium ion secretion Control Of Aldosterone Secretion By K+ and Na+

17. Helps efficiently eliminate foreign compounds from the body. • Functions of organic ion secretory systems • Proximal tubule contains two types of secretory carriers • For organic anions • For organic cations • The organic ion secretory systems serve three important functions: • Organic ions such as Prostaglandin, epinephrine – after completing their action must be removed from the blood. • Non filterable organic ions also removed by secretion. • Chemicals, food additives, non nutritive substances. • Drugs – nonsteroidal anti inflammatory drugs (NSAID), antibiotics. ORGANIC ANION AND CATION SECRETION

18. PAH is an organic acid. • Used for measurement of renal plasma flow. • Both filtered and secreted. • PAH transporters located in peritubular membrane of proximal tubular cells. • There are parallel secretory mechanism for secretion of organic bases like quinine and morphine. PAH –EXAMPLE OF SECRETION

19. Urea is freely filtered – 50% reabsorbed in PCT. • Urate is freely filtered • In PCT there is reabsorption and secretion takes place. • In the initial & middle part of PCT reapsorption is more than secretion. • In the distal portion of PCT moderate amount of urates are secreted. UREA and Uric acid SECRETION

20. REFERENCES • Human Physiology by Lauralee Sherwood, Seventh edition • Text book Physiology by Guyton & Hall,11th edition • Text book of Physiology by Linda S. Contanzo, Third edition