Physiol 2130 - Module 11 Renal System PDF

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PHYSIOL - Module 11

RENAL SYSTEM Introduction - Consists of the kidneys, ureter, bladder and urethra - Kidneys are responsible for regulating: - Water balance - Electrolyte levels - Blood pH - Long-term regulation of arterial pressure Functions of the Kidneys 1. Remove nonessential substances from the plasma - Waste metabolites, excess water and electrolytes - Removes drugs, food additives and vitamins that are excreted in the urine 2. Recover any essential substances - Glucose - They don’t produce water of electrolytes, they conserve them to reduce the amount removed from the body - “Think of a sponge” - Also, act as an endocrine gland that produces hormones or hormonal system components like: - Erythropoietin, renin, vitamin D, stanniocalcin Anatomy of Kidneys - Fist sized - Consists of: - Renal cortex - Middle renal medulla - Inner calyces - Drains into a central renal pelvis - Central renal pelvis - Drains into ureter - Ureter - Functional units of the kidneys are in the renal pyramids, they’re called the nephrons - Each nephron drains through a collecting duct into a calyx Anatomy - Blood Supply of the Kidneys - Flows through the renal artery which branches into several interlobar arteries that branch into arcuate arteries - Blood in arcuate arteries flow through the interlobar arteries which supply the nephrons - Blood is then drained out into the interlobar veins then to the renal veins - ‘Note: veins = into heart, arteries = away from heart’

PHYSIOL - Module 11

Anatomy - The Nephron - There are about 1 mill nephrons per kidney - They filter the blood, reabsorb essential stuff and excrete nonessential molecules and waste - A nephron is made of a highly coiled hollow tube surrounded by a complex blood supply - The glomerular capsule (Bowman’s capsule) surrounds a highly permeable capillary bed, the glomerulus - The structure is also called the renal corpuscle (bowman’s capsule + glomerulus) - The tubular structure of nephrons consist of (in order) 1. Proximal convoluted tubule (very coiled) 2. Descending and ascending loop of henley 3. Distal convoluted tubule 4. Collecting duct Anatomy - Blood Supply of the Nephron 1. Renal artery carries blood to the interlobular arty → afferent arteriole 2. Blood enters the glomerulus for filtration to occur and reaches the efferent arteriole 3. Blood enters the peritubular capillaries (the capillary network of around the nephron tubes) 4. Drains into the interlobular vein and back to the renal vein

Renal Corpuscle - Made of the glomerular capsule - Blood is filtered here and called glomerular filtration - The fluid that is filtered from the blood enters the capsule (capsular space) - is the filtrate - Facilitated by highly permeable capillary endothelium, surrounded by podocytes

PHYSIOL - Module 11

Processes along the Nephron - Each section has a different purpose - Filtration, reabsorption and secretion - Filtration - movement of fluid through the glomerular capillary due to hydrostatic pressures - Reabsorption - the movement of a substance from the lumen of the nephron back into the blood - Secretion - movement of substance from blood into the lumen on the dephron - Excretion - removing substance from the body - Together, we get: - Excretion = filtration + secretion reabsorption

Glomerular Filtration - The filtrate contains the same substances as plasma with the exception of large plasma but it doesn’t have large proteins + RBCs - It’s affected by very permeable capillaries → making the glomerulus and starling forces - Glomerular capillaries have many fenestrations - Special epithelial cells, podocytes surround the capillaries and allow filtration because of their large slits between pedicles

Glomerular Filtration - Starling Forces - They cause the bulk movement of fluid across capillaries because of a combo of hydrostatic and colloid osmostic forces

PHYSIOL - Module 11

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- Similar in glomerular capillary but diff pressure of ea The blood hydrostatic pressure is ~60mmHg, this is ab twice the regular - Allows for fluid filtration into Bowman’s capsule - Pressure is due to diameter difference between the afferent (large) and efferent (small) arterioles - It is the pressure caused by the confined space of the Bowman Capsule as it fills with filtrate The colloid osmotic pressure is -32mmHg bc of plasma proteins - Allows for reabsorption of fluid into plasma - No colloid osmotic force in the glomerular capsule bc few proteins are filtered The capsular hydrostatic pressure is -18mmHg - Causes reabsorption of fluid - Therefore, resulting net filtration pressure is 10mmHg out of the glomerulus into the capsular space

Glomerular Filtrate Rate (GFR) and Filtered Load - Kidney filters 180L/day - GFR is the volume of fluid that’s filtered by the glomerulus during a certain period of time - The filtered load is the of other substances the kidneys filter per day and can be calculated:

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Filtered load and GFR can indicate the health of your kidneys and if they’re functioning right - Glucose is not excreted in urine bc it gets reabsorbed by the nephron in healthy ppl - Sodium can be found in urine bc it is both filtered and excreted The urine concentration and amount of solute excreted gives info on the health/fxn of kidneys as well - Urine concentration: the amount of solute excreted per volume of urine (g/L) - Amount of solute excreted: actual amount (g) of solute in the urine The amount reabsorbed is the mount of filtered substance that is taken up by the kidneys

PHYSIOL - Module 11

Example - you ate a bag of salty chips and now you need to urinate, calculate the concentration of Na+ in the urine (g/L)

PHYSIOL - Module 11

Tubular Transport Mechanism - Reabsorption and secretion happen with different substances in a regulated or non-regulated manner - Both involve multiple transport mechanisms including active transport, secondary active transport, facilitated diffusion, simple diffusion, and osmosis - in the case of water Tubular Transport Mechanism - Reabsorption - Over 99% of filtered substances in the glomerulus are reabsorbed back into the circulation at diff dites along the nephron - Two transport routes can be taken: - Paracellular transport and/or transcellular transport - Tubular cells are joinged by tight junctions which don’t allow substances to cross b/w the cell - In th enephron, these are kinda leaky so some substances can diffuse by a process called paracellular transport

Tubular Transport Mechanism - Reabsorption: The Na+/K+ Pump - Many transport mechanisms in the nephron reply on this pump (is an active transport mech) - Pump needs ATP to move 3 Na+ out and 2 K+ in - For movement to occur a high concentration of Na+ (outside) + high concentration of K (inside)

PHYSIOL - Module 11

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In secondary active transport, Na concentration gradient is made by the pump and is used to power other transporters - As Na+ moves into the cell down the c gradient, other substances will either movie in/out with Na+ - Includes the Na+/glucose co-transporter and the Na+/H+ exchanger - Na+/glucose co-transporter is on the luminal side, per 1 entering Na cell 1 glucose is carried in along - Is a membrane protein - Driven by K+ entering cell - The Na+/H+ exchanger is on the luminal side, moves 1 H+ out for every Na+ entering - Driven by Na+ exiting cell

Tubular Transport Mechanism - Secretion - Unwanted stuff from the blood enters the lumen of the nephron - Stuff → H+ and K+ - Secretion is generally a hormonally regulated process, in some cases, it can happening w/o any hormone control (non-regulated) - The process does rely on the pump

Tubular Transport Mechanisms

PHYSIOL - Module 11

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Na+ reabsorption → proximal tubule, ascending limb, early distal tubule - Non-regulated mechs - The proximal tube can be hormonally reg. by angiotensin II - aldosterone can reg the distal tubule and collecting duct H2O reabsorption → proximal tubule, descending limb - Non-regulated mechs - Reaborbed by ADH in the late distal tubule and collecting duct K+ - Reabsorption → proximal tubule and ascending limb - Secretion → ascending limb (low #), distal tubule + collecting duct (high #) - ADH influences distal tubule and collecting duct H+ secretion → proximal tubule, ascending limb, late distal tubule, collecting ducts - Hormonally/non-hormonally reg.

Proximal Convoluted Tubule - Reabsorption of Na+, Glucose, and Amino Acids - Reabsorbs ~66% of total filtrate - Due to Na+ concentration gradient (created by pump), Na+ can be reabsorbed by simple diffusion, Na+/glucose cotransporter, Na+/H+ exchanger - Amino acids are reabsorbed along the nephron section by the Na+/Amino acid co-transporter - Similar to the Na+/glucose co-transporter - The Na+/glucose co-transporter will reabsorb all glucose in healthy people - Not in ppl with diabetes meticulitis Proximal Convoluted Tubule - Diabetes Mellitus - Disease that affects the pancreas’s ability to make insulin - Insulin → Glucose storing hormone - w/o insulin, large quantities of glucose are filtered by the glomerulus that can’t be reabsorbed by the Na+/glucose co-transporter - Common symptom of this disease → sugar in urine - Bc the co-transport system is a form of secondary active transport, it can be saturated

Proximal Convoluted Tubule - Reabsorption of Water - After Na+, glucose and amino acids have been reabsorbed, the filtrate will have a lower solute concentration (higher H2O concentration) - Water will move down its c gradient by osmosis which lets it be reabsorbed by both paracellular transport between the cells, and by transcellular transport across the cells

PHYSIOL - Module 11

Proximal Convoluted Tubule - Potassium and Chloride - 65% of K and Cl are reabsorbed here and done through two types of paracellular transport (nonregulated) 1. Solvent drag: reabsorption of K+ w/ H2O movement - As H2O moves b/w the cells, dissolved substances in filtrate are carried along (K+) 2. Simple diffusion as H2O is reabsorbed through the tubule cells, K+ remain n filtrate - As more H2O is reabsorbed, K+ becomes more concentrated which causes simple diffusion

Reabsorption of Filtrate Back Into the Circulation - Material returned to the circulation - Must leave the cells and enter the interstitial space - Na+ uses Na+/K+ pump - Glucose and amino acids are transported across the basal membrane by specific facilitated diffusion transporters - K is already in the space bc it was reabsorbed by paracellular transport - Once in the interstitial fluid, they’re reabsorbed into circulation by Starling Forces - H2O and molecule reabsorption from interstitial space back into the peritubular capillaries occur bc of Starling Forces - Starling Forces are different around the tubule cells than typical capillaries - Hydrostatic force (PC) = 13mmHg - Interstitial hydrostatic force (PIF) = 6mmHg - Osmotic force due to proteins in the plasma (πp) = 32mmHg - Interstitial osmotic force (πIF) = 15mmHg - Net Filtration Pressure (moving into fluid) = (P c-PIF) - (πp -πIF) = -10mmHg - 10mmHg back into the capillary - Large osmotic pressure bc of plasma proteins: - Large bc during glomerular filtration, almost all substances were filtered except large proteins Proximal Convoluted Tubule - Concentration of Filtrate - After reabsorption of molecules and water, the filtrate concentration leaving the proximal tubule won’t change much from what it originally was - ~290-300 mOsm/kg water

PHYSIOL - Module 11

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Same proportion of solutes and water are being reabsorbed in the proximal tubule...