Lecture 3 (Tubular Functions I) PDF

12/8/2024 Dr. Mona Farouk M. Mansour Assistant professor of physiology FOM/SCU 1 Points to be covered by the lecture: Tubular reabsorption and secretion. Distinguish between active (primary and secondary)...

12/8/2024 Dr. Mona Farouk M. Mansour Assistant professor of physiology FOM/SCU 1 Points to be covered by the lecture: Tubular reabsorption and secretion. Distinguish between active (primary and secondary) transport, facilitated diffusion, and passive diffusion based on energy source and carrier protein involvement. Describe the contribution of the major nephron segments to the reabsorption of the filtered load of solute and water. Transport properties of nephron segments Describe the regulation of proximal tubule reabsorption. Describe the cellular mechanisms for the transport of inorganic and organic solutes and water by the major tubular segments. 2 1  12/8/2024 Renal Tubules 0 Loop Of Henle 3 Functional Histology: 4 2  12/8/2024 Artery Renal Renal Vein 5 Tubular Functions Glomerular Filtra on − (Tubular Reabsorp on + Tubular Secre on) 6 3  12/8/2024 ESSENTIAL VRIABLE DEPEND ON BODY NEEDS WASTE N.B.: Essential substances such as Glucose, amino acids and vitamins. 7 8 4  12/8/2024 TUBULAR REABSORPTION Peri- tubular ii i c b a 9 ROUTES OF TUBULAR REABSORPTION Reabsorption of substances from tubular lumen into the peri-tubular capillary occurs by two routes: 1. Transcelluar route: = the reabsorbed substances move through the cell. It includes transport of substances from: a. Tubular lumen into tubular cell through luminal surface of the cell membrane. b. Tubular cell into interstitial fluid. c. Interstitial fluid into capillary. 2. Paracellular route: = the reabsorbed substances move through the intercellular space. It includes transport of substances from: i. Tubular lumen into interstitial fluid present in lateral intercellular space through the tight junction between the cells ii. Interstitial fluid into capillary 10 5  12 11 Non-Selective transport (Bulk Flow) MECHANISMS OF TUBULAR REABSORPTION Selective active/passive transport 12/8/2024 6  12/8/2024 I. Transport From Tubular Lumen To Renal Interstitium (Selective) Active Reabsorption: Passive Reabsorption: When?  When? Ac ve reabsorp on→ if any one of the steps Passsive reabsorp on→ all steps in in the transepithelial transport of a substance the transepithelial transport of a requires energy, even if the four other steps are passive. substance from the tubular lumen to the plasma are passive. Active transport=It is the movement of molecules against the electrochemical  Passive transport= It is the gradient. It needs energy (ATP). movement of molecules along the Examples: Substances reabsorbed actively electrochemical gradient. It does from the renal tubule are sodium, calcium, not need energy. potassium, phosphates, sulfates,  Examples: Substances reabsorbed bicarbonates, glucose, amino acids, passively are chloride, urea and ascorbic acid, uric acid and ketone bodies. water. 13 Cell Membrane Transport Mechanisms 14 7  12/8/2024 ACTIVE TRANSPORT The primary active transporters in the kidneys that are known include sodium-potassium ATPase, hydrogen ATPase, hydrogen-potassium ATPase, and calcium ATPase The secondary active transporters in the kidneys: Na+- Glucose cotransporter Na+- Amino acid cotransporter Na+/H+ countertransport 15 16 8  12/8/2024 II. Transport from renal interstitium to peri-tubular capillary (Non- selective) The substances are non-selectively transported from renal interstitium to the peri-tubular capillary by Bulk Flow, which depends on pressure gradients between hydrostatic and colloid osmotic forces in the renal interstitium and peritubular capillaries. The normal rate of peri-tubular capillary reabsorption is about 124 ml/min. 17 The Tubular Reabsorptive Forces Include: (1) Hydrostatic pressure inside the peritubular capillaries (peritubular hydrostatic pressure [Pc]), which opposes reabsorp on → 13 mmHg. (2) Hydrostatic pressure in the renal interstitium (Pif) outside the capillaries, which favors reabsorp on → 6 mmHg. (3) Colloid osmotic pressure of the peritubular capillary plasma proteins (πc), which favors reabsorp on → 32 mmHg. (4) Colloid osmotic pressure of the proteins in the renal interstitium (πif), which opposes reabsorp on → 15 mmHg. 18 9  12/8/2024 19 SITE OF TUBULAR REABSORPTION Reabsorption of the substances occurs in almost all the segments of tubular portion of nephron. Proximal convoluted tubule Distal It reabsorb 88% of the Loop convoluted filtrate, including : Of tubule glucose, amino acids, Henle sodium, sodium, potassium, calcium, sodium, and calcium, bicarbonates, chlorides, Chloride. bicarbonates, phosphates, urea, uric acid and water and water 20 10  12/8/2024 21 1 Secondary Active Transport SGT2 GLUT2 Facilitated Diffusion 3 2 22 11  12/8/2024 1 2 23 24 12  12/8/2024 Loop Of Henle  The thin descending limb, where water passively diffuses into the hypertonic renal medulla through leaky “tight” junctions on the epithelium.  TALs (thick ascending limb) of the loop of Henle have tight junctions that restrict water movement, making these segments water impermeable.  The important transport protein in the TAL is the apical Na+/K+/2Cl− transporter.  The TAL absorbs most of the remaining luminal K+ at this transporter.  Reabsorption of the majority of remaining tubular calcium and magnesium occurs via the paracellular route in this thick segment.  Solute in this segment is transported without water resulting in a drop in the filtrate osmolality to low levels (100 mOsm) as compared to normal plasma osmolality of 300 mOsm.  Because solute transport without water movement occurs in this segment, the TAL of the loop of Henle is called the diluting segment, and movement of solutes into this medullary interstitium increases the hypertonicity of interstitial tissue in this area 25 26 13  12/8/2024 Distal convoluted tubule The distal tubule lining cells have tight junctions, water and electrolytes cannot passively diffuse out of them, and tubular fluid remains hypotonic within this cortical segment. In the early distal tubule, The apical Na+/Cl− transporter contributes more to this hypotonicity by reabsorbing more ions from the tubular fluid. The parathyroid hormone (PTH) acts on the DCT to induce increased Ca2+ reabsorption. In the late distal tubule, Intercalated cells are involved in H+ secretion and HCO3 − reabsorption Principal cells can be induced to secrete K+ if the adrenal hormone aldosterone is present. Because the apical surface has a Na+ channel to absorb Na+, and the apical membrane has K+ channels. The net effect in this segment is that as Na+ is reabsorbed, K+ is secreted. 27 Collecting duct Water reabsorption in the distal nephron collecting ducts is regulated by ADH (vasopressin) from the posterior pituitary. This hormone induces the insertion of aquaporins on the cell apical surface to increase water permeability and reabsorption 28 14  12/8/2024 29 Sodium handling Na+ reabsorption is vital for reabsorption of other substances: In PCTs (67% reabsorbed) Na crosses the luminal border by a cotransport carrier. In the ascending limb of the loop of Henle (25% reabsorbed), along with K, Cl reabsorption. In the distal and collecting tubules (8%) is variable (under hormonal control) regulating ECF volume Na+ reabsorption  along all renal tubules except descending LOH 30 15  12/8/2024 Potassium handling In the PT, K reabsorption (67%) occurs paracellularly by Solvent drag along with the water reabsorption. In the ascending limb of the loop of Henle (20%) reabsorbed, along with Na, Cl reabsorption. In the distal and collecting tubules, K secretion is variable under hormonal control, dietary K, acid base balance 31 Glucose, and Amino-Acid Reabsorption Glucose and amino acids are transferred by secondary active transport. With this process, specialized cotransport carriers located in the proximal tubule simultaneously transfer both Na and the specific organic molecule from the lumen into the cell. Once transported into the tubular cells, glucose and amino acids passively diffuse down their concentration gradients across the basolateral membrane into the plasma, facilitated by a carrier that is not dependent on energy. 32 16  12/8/2024 TRANSPORT MAXIMUM “TM” Each carrier is specific for the types of substances it can transport; The maximum reabsorption rate is reached when all the substance specific carriers are fully occupied or saturated, Transport maximum (Tm) is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule (referred to as tubular load) exceeds the capacity of the carrier proteins and specific enzymes involved in the transport process. When the filtered load exceed the Tm, the substance start to appear in urine. All actively reabsorbed substances have a tubular maximum. The plasma concentration at which the Tm of a particular substance is reached and the substance first starts appearing in urine is called the renal threshold. 33 Tm Of The Glucose The Tm for glucose averages 375 mg/min (=3 times the normal filtered load of glucose); that is, the glucose carrier mechanism is capable of actively reabsorbing up to 375 mg of glucose per minute before it reaches its maximum transport capacity. The overall transport maximum for the kidneys, which is normally about 375 mg/min, is reached when all nephrons have reached their maximal capacity to reabsorb glucose. 34 17  12/8/2024 However, when the plasma concentration of glucose rises above about 200 mg/100 ml, increasing the filtered load to about 250 mg/min, a small amount of glucose begins to appear in the urine. This point is termed the threshold for glucose. Why glucose appear in the urine (at the threshold) occurs before the transport maximum is reached?  Because not all nephrons have the same transport maximum for glucose, and some of the nephrons therefore begin to excrete glucose before others have reached their transport maximum. 35 36 18  12/8/2024 TUBULAR SECRETION Tubular secretion is the process by which the substances are transported from blood into renal tubules. It is also called tubular excretion. Secreted substances are secreted into the lumen from the peri-tubular capillaries through the tubular epithelial cells. Examples: 1. Potassium is secreted actively by sodium potassium pump in proximal and distal convoluted tubules and collecting ducts 2. Ammonia is secreted in the proximal convoluted tubule 3. Hydrogen ions are secreted in the proximal and distal convoluted tubules. 4. Urea is secreted in loop of Henle. 37 References: Chapter 13 Chapter 6 Chapter 28 38 19  12/8/2024 39 20