Lecture 26: Urinary 2: The tubular Function Flashcards
What are the events occurring in the tubules?
-Glomerular filtration = bulk movements (water + dissolved substances) –> tubular fluid composition close to a protein free plasma
-In the tubule, fluid will be transformed into urine
-Reabsorption: water and dissolved substances from tubular lumen to peritubular capillaries
-Secretion: substances transported from the peritubular capillaries to the tubular lumen
What are the 2 main types of active reabsorption?
- Primary active reabsorption
-ATP is used to transport a substance against the concentration gradients
-Used for Na+ : Na/K pumps in the epithelial cells from the basolateral membrane pump Na+ towards interstitial fluid –> then Na+ diff cues in the capillaries
-Since the pumps maintain low level is Na+ in the epithelial cells –> Na+ diff cues from the lumen
-K+ easily leaks back out of the cell into the interstitial fluid - Secondary active transport
-Transport of 1 solute coupled to transport of another: case of glucose coupled to Na+ transport
-In addition to diffusion, Na+ also transported into epithelial cells by specific membrane transport proteins
-Once inside the cell, glucose moves along the gradient to the capillary
-Other modules like AA and several organic molecules use that transport
-H+ also couples to the Na+, but moves towards the tubular lumen
What is the passive transport?
-When conc. of a substance (neg ions, drugs, environmental toxins) in the lumen increases to higher levels than in epithelial cells
-if CELL MEMBRANE PERMEABLE to that substance
-Substances diffuse back out of the tubular lumen
-Molecular size and liposolubulity determine what is passively reabsorbed
-This is the case for urea (50-60% of filtered urea is reabsorbed)
What is tubular secretion?
-Only for selected substances
-From the peritubular capillaries –> across tubular cells –> into the lumen
-Some by primary active transport
-One system for organic acids
-One system for organic bases
-Others by secondary active transport; case of H+
-Some by passive diffusion, this is the case for several steroid hormones, drugs etc (that wouldn’t normally be at a high level in blood)
What is the tubular handling of glucose?
-Filtered as easily as water –> glucose concentration in glomerular filtrate =plasma concentration
-100% reabsorption of glucose ONLY IN PROXIMAL TUBULE
-Occurs by secondary active transport
-Kidney does not participle in regulating glucose levels just prevents its loss
-Normally, no glucose will appear in urine
-Unless glucose conc. in plasma extreme
-The lowest plasma conc. at which glucose can be detected in urine= RENAL THRESHOLD FOR GLUCOSE
Explain the renal threshold for glucose from the graph in more detail.
-Splay: deviation from an ideal curve
-Splay not a short deflection: all nephrons dont have same length of proximal tubule–> some still reabsorbing while others are out
-When all nephrons reached their maximum reabsorption capacity, the kidney (as a unit) is at its max glucose concentration 3x higher than normal in plasma
-After Tax: excretion curve parallels the filtration levels, there is a lot of room for increase in plasma glucose
What is diabetes mellitus?
-Glucose in urine (sweet pee)
2 main casues
-Insulin regulation of blood glucose doesn’t work (lack or impaired insulin) –> glucose levels in plasma increase dramatically passed the Tmax–> kidney can not handle all of it –> glucose excreted
-Genetic defect affecting the transport mechanism os glucose in the proximal tubule –> reduced Tax –> glucose excreted even when plasma levels are normal (happens in dog and humans)
What happens at the tubular level for handling proteins?
-Should have been blocked by neg charge in glomerulus but some small will pass
-Do not pass through glomerular membrane (not normally present in glomerular filtrate) except small peptides and proteins
-Reabsorbed by epithelial cells of the proximal tubes by endocytosis (small peptides come into contact with proximal tubule engulf and bring back in)
-Broken down into AA in epithelial cells
-Residual amounts of proteins in urine can sometime be observed (dogs)
What happens with proteins in the urine?
-Not normal, glomerulus should not let them pass
-Main reason for protein leakage is an imbalance of charge in glomerular membrane
-Basal lamina negatively charged
-Proteins are neg. charged and are repulsed by neg membrane charges
-If membrane looses it polarity some proteins can pass through (physically damaged)
What is tubular handling of ions controlled?
-Most happens at the level of the prox. tubule
-Reabsorption of many ions equals the amount filtered –> low conc. in urine
-Most of the reabsorption of ions is hormonally controlled = regulated
-For most ions, intestinal absorption affect the plasma levels and thus the filtration
What happens in the reabsorption of Na+?
-Kidney is the most important organ in Na+ control
-Na+ is the most important factor regulating extracellular and blood volumes
-In addition, transport of other substances also coupled to Na+ (secondary active transport)
-Reabsorption of glucose, AA, HCO3, PO4
-Secretion of H+ and K+
-Energy spent in Na+ transport represents 80% is the metabolism of the kidney
Steps:
1. From fluid from tubule to epithelial cells
2. Epithelial cells to interstitial fluid
3. Interstitial fluid to blood
How does aldosterone and Na+ affect transport?
-Most important factor stimulating Na+ reabsorption in the distal tubule and collecting duct
-Steroid hormone (lipodsoluble) synthesized and released by the adrenal cortex= mineralocorticoid
-Induced the (# of pumps) synthesis of Na+ channels and pump in epithelial cells= increase Na+ transport from the lumen to the epithelial cells (channels) and from the epithelial cells to the interstitial fluid (pumps)
-If no aldosterone, all the Na+ entering the distal wobble will be excreted in urine= death within a couple of days
What happens with the reabsorption of K+?
-Normally inside cells: ECF content relatively low
-Needs to be maintain within a narrow range
-Actively reabsorbed in proximal tubule
-Secreted in distal tubule and collecting duct
-Since 100% filtered is reabsorbed, changes in K+ mainly due to secretion
-Since secretion via Na+/K+ pump in distal tubule, when Na+ reabsorbed - K+ secreted (and vice versa)
-K+ conc. also controls aldosterone release
What is the reabsorption of calcium?
-In plasma 50% of Ca2+ is bound to proteins
-Only free form can be filtered in the glomerulus
-Most of the reabsorption occurs in the proximal tubule
-However, the regulated reabsorption occurs in the ascending limb of the loop of henle the distal tubule and collecting ducts
-Parathyroid hormone (PTH) stimulates the reabsorption
-Generally 1-2% of the filtered Ca2+ is excreted
What happens with the tubular reabsorption of water?
-Very important to maintain blood volume
-Occurs by 2 mechanisms
-B/w epithelial cells through tight junctions
-Through epithelial cells (aquaporins) water channels
-Since its a diffusion process (osmosis) it is influences by movements of Na+
-Most reabsorption occurs in the proximal tubule
-However most structures possess aquaporins
-Except the ascending limb of the loop of henle
-In the distal tubule and collecting duct, aquaporins up regulated by ADH=increase water reabsorption
