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375 Cards in this Set
- Front
- Back
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What are the kidney functions? (4)
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1) Regulation of water and inorganic ion balance
2) Removal of metabolic waste products from the blood and their excretion in the urine. 3) Removal of foreign chemicals (ie. drugs) from the blood and their excretion in urine 4) Production of hormones/enzymes |
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What are the enzymes/hormones that the kidney produces?
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Erythropoeitin, Renin, and 1,25-dihydroxyvitamin D
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What does erythropoietin do?
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It controls erythrocyte production. It is synthesized in the epithelial cells in the proximal tubule.
It acts on bone marrow to stimulate production of RBCs. |
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How does the kidney's function to produce erythropoietin correlate in renal disease?
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Those with renal disease are highly anemic. (Deficiency of Hb, component of RBC's)
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What does renin do?
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It is an enzyme that controls the formation of angiotensin and influences BP and Na balance.
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Where is angiotensinogen produced?
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the liver
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What does renin do to angiotensinogen?
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Converts angiotensinogen to angiotensin I.
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What happens to angiotensin I in the blood? What is a consequence of the product?
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It is converted to angiotensin II. It is an important vasoconstricter. Can come back and act on kidney vessels, regulating filtration of blood.
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What is 1,25-dihydroxyvitamin D?
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It is an active vitamin that influences sodium balance.
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What type of cells are originally in the kidney?
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Mesenchyme
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What invades the mesenchymal cells?
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The epithelial uretic duct
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What happens after the epithelial uretic duct invades dissociated non-polarized mesenchyme?
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The mesenchymal cells condense around the ureteric bud tip and convert into renal epithelium
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What are the stages after mesenchymal cells have condensed around the tip, for conversion to renal epithelium?
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Vesicle, comma, and S-shaped body.
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What happens in the comma-shape stage?
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The tubules elongate.
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What happens to the S-shape body?
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It elongates and gives rise to the nephron segments. This is the filtration apparatus
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What happens to the uretic bud during kidney development?
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It branches, elongates, and eventually forms the COLLECTING DUCT SYSTEM.
This includes: Proximal and distal convoluted tubules, glomerulus and loop of henle. |
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What do growing blood vessels form during renal system development?
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Glomeral capillaries
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How do we survive until birth without a functioning kidney?
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The fetal blood is cleaned by the umbilical cord.
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How many organs do the kidneys exist as?
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The kidney exists as PAIRED organs
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What is the size of each kidney?
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Approx 150 g each. About the size of a clenched fist
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Where are the kidneys located?
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Behind the peritoneum on either side of the vertebral column against the posterior abdominal walls.
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How are the kidneys protected?
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They are partially protected by the rib cage.
Large muscles near the ribcage also. They are encapsulated by a layer of fat tissue which cushions them. |
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What does renal mean?
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Pertaining to the kidneys. In latin!
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What structure do the kidneys lie under?
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The diaphragm
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What structure connects the kidneys to the bladder?
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The ureter
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What structure connects the bladder to the outside?
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Urethra
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What is the bladder?
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It is an organ that can expand and contract. It is made of smooth muscle. Urine produced in the kidneys travels there is stored until urination. Urine is the way in which the body can rid of stuff filtered from the blood in the kidney.
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What is the outermost layer of the kidney? What occurs here?
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The renal cortex: filtration of the blood takes place here.
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What is the second outermost layer of the kidney? What occurs here?
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The renal medulla: The filtrate produced in the cortex is modified to eventually produce urine.
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How does the urine get to the ureter?
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It is connected by the renal pelvis.
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How is blood pumped to the kidney from the heart?
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Through the renal artery
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How much percentage of the blood goes to the kidney per unit time?
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20-25% of the blood goes to the kidney.
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What is the purpose of the renal vein?
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Cleared blood exits the kidney via renal vein
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Where does the renal artery branch first and into what?
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The renal artery first branches in the renal pelvis to form the INTERLOBAR arteries.
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What do the interlobar arteries branch into and where? How do they branch?
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The interlobar arteries branch at the BORDER of the CORTEX/MEDULLA. They branch LATERALLY to form the
ARCUATE ARTERIES. |
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How do the arcuate arteries bring blood to the cortex of the kidney?
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They divide further into INTERLOBULAR arteries.
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What is the smallest division of the renal artery and what is its purpose?
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The smallest division of the renal artery is the AFFERENT ARTERIOLES. These bring blood to each filtration unit in the kidney
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What are the subunits of the kidney and how many does the kidney contain?
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The subunits of the kidney are called NEPHRONS. Each kidney contains approximately 1 million.
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What are the two components of the nephron?
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The renal corpuscle and the tubules
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What is the renal corpuscle and what are its divisions?
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The renal corpuscle is the filtration apparatus of the kidney. It contains the GLOMERULUS and BOWMAN's CAPUSCLE.
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What is the glomerulus?
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Capillary loops
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What does the tubule do? Where does it end up?
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It modifies the FILTRATE and produces URINE.
This is a long segment that goes to the COLLECTING DUCT, passing through the RENAL MEDULLA. |
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How are glomeral capillaries formed?
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The afferient arteriole enters the glomerulus.
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What is it called when the arterioles exit the glomerulus?
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Efferent arterioles
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What is the key characteristic of the glomeral capillaries?
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They are incredibly leaky.
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How does plasma (the liquid portion of blood) get to Bowman's space from the glomeral capillaries in the glomerulus?
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Plasma can travel freely through holes (BOWMAN'S CAPSULE) entering the space (BOWMAN'S SPACE).
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After being filtered into Bowman's space, where does the filtrate travel first?
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Proximal Convoluted Tubules
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How are the epithelial cells specialized in the proximal convoluted tubule?
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They contain microvilli- which greatly expands the SURFACE AREA of the tubule.
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What does the increased surface area in the PCT allow?
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EXCHANGES between epithelial cell and LUMEN. This is important for RE-ABSORPTION.
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What is re-absorption?
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Taking back "good stuff" from the filtrate into circulation.
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Where does the filtrate pass after the proximal convoluted tubule?
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The filtrate goes to the DESCENDING THIN LOOP OF HENLE'S LOOP.
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What is the purpose of the loop of Henle?
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Removes salt and water INTO circulation (or out)
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At what point does the PCT descend from the cortex to the medulla of the kidney?
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Through the proximal straight tubule
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After the thin descending loop of Henle, where does the filtrate pass?
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The thin ASCENDING loop of Henle.
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After the thin ascending loop of Henle, where does the filtrate pass?
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The filtrate passes through the THICK ascending loop of Henle.
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What does the tubule become when going back into the cortex from the medulla?
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The DISTAL CONVOLUTED TUBULE
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What is the DCT connected to?
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The collecting duct
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What are the divisions of the collecting duct?
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Cortical and Medullary
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What is the purpose of the collecting duct?
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FINE-TUNING. They do not take up alot of salt or water.
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What is the area in the kidney system that is for HORMONAL regulation?
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Distal tubules + collecting ducts
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Is it possible for more than one filtration unit to end up in the same collecting duct?
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Yes. A few filtration units can open up into the same collecting duct.
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What does the medullary collecting duct portion open up into?
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The renal pelvis
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What is the glomerulus?
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Entangled capillary loops surrounded by the Bowman's capsule.
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What are the components of the capillary wall in the glomerulus?
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Endothelial cells, glomerular basement membrane, epithelial visceral cells
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What is another name for Epithelial visceral cells?
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podocytes
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How are the podocytes arranged and where do they come from?
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They are arranged in a MONOLAYER. The epithelial cells come from mesochymes.
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Where is the glomerular basement membrane located and what is its purpose?
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It is located between the endothelial and epithelial cells. It is a gelatinous layer and acts as a CRUDE FILTER.
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What is the MAIN purpose of the glomerulus?
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It filters BLOOD to make URINE
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What type of layer is the outermost part of the Bowman's capsule?
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The parietal layer
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What is the portion of the Bowman's capsule that is close to the capillary portion of the glomerulus?
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The visceral layer containing the podocytes.
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Where are the macula densa located?
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In the end of the THICK ASCENDING LIMB OF THE LOOP OF HENLE and the DISTAL TUBULE. They are specialized cells. They are small, tightly packed epithelial cells. And appear darker.
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What is the purpose of the macula densa?
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They are the site of hormone synthesis.
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What is the difference between prostaglandin and renin?
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Prostaglandin typically acts as a vasodilator and renin typically acts as a vasoconstrictor,
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What type of cell processes do podocytes form in the capillary wall?
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Foot processes
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How does fluid travel from inside the capillary to the Bowman's space?
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Through hole like- fenestrae in the endothelial cell layer, through the basement membrane to filtration slits and finally to the capsular space.
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Describe how the filtration barrier functions in the endothelial cells of the glomerular wall.
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Fluid passes through holes known as FENESTRAE in the ENDOTHELIAL CELLS.
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Describe how the filtration barrier functions in the basement membrane of the glomerular wall.
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After passing through the FENESTRAE, The basement membrane acts as a crude filter, removing CHARGED MOLECULES and BIG PROTEINS, which cannot pass through.
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Where is the capsular space located?
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Within the PODOCYTES
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What are the peritubular capillaries?
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Peritubular capillaries are tiny blood vessels that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron.
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What are the three processes of urine formation?
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1. Glomerular filtration
2. Tubular secretion: gets rid of everything bad 3. Tubular reabsorption: to get everything good back into the blood. |
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Where does urine filtration begin?
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The filtration of plasma from the glomerular capillaries into Bowman's space.
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What is glomerular filtrate composed of?
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It is cell free. It does NOT contain proteins, but retains everything else from plasma in about the same concentrations.
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Describe secretion
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Substances pass from the blood into the filtrate in the tubules and are then secreted.
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Describe in simple terms the process of re-absorption.
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Substances pass from the filtrate in the tubules back to the peritubular capillaries.
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How is the amount EXCRETED calculated?
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Amount filtered + Amount Secreted - Amount Reabsorbed.
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How are drugs secreted?
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They are NOT filtered in the glomerulus. Transporters at the interstitial side of the epithelial cells recognize the drugs and pound them through- they are then secreted.
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What are the percentages of water and sodium that are reabsorbed?
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99% water. 99.5% sodium
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How much glucose is usually excreted in the urine? What is the problem in diabetes?
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Normally ALL glucose is reabsorbed. In diabetes, you have an excess of sugar in the plasma. Transporters moving glucose from the lumen to the blood are SATURATED. Therefore some glucose passes into the urine.
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Para-amino-hippurate is an example of what type of substance.
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A substance of which the majority is EXCRETED. A small amount is reabsorbed.
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How do homeostatic mechanisms regulate urine production?
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When the body content of a substance is abnormal, mechanisms change the rates of filtration, absorption and secretion to restore homeostasis.
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What is FILTERED by glomerular filtration? What is allowed to pass through?
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Water is allowed to pass from the plasma to the filtrate. As well as low molecular weight substances.
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How does the crude filter of the BM prevent fatty acids from passing through?
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The basement is negatively charged, and therefore REPELS the negatively charged fatty acids that are protein bound.
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What substances are retained from passing into the filtrate at the level of glomerular filtration?
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Cells, proteins (albumin, globulins), and protein-bound substances such as 1/2 of calcium ions, and fatty acids)
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What are the forces favoring filtration? What is the pressure value?
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The glomerular capillary blood pressure allows liquid to go into the Bowman's space. This is the pressure generated by the heart. It is approx 60 mmHg.
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What are the forces opposing filtration? What are the pressure values?
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The fluid pressure in the Bowman's space. As filtration proceeds, liquid fills in the space and generates its own pressure, approx 15 mmHg.
The osmotic (oncotic) force due to protein in the plasma. An increase in protein concentration results in sucking up water that would normally pass into the filtrate. |
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What does GFR stand for?
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Glomerular Filtration Rate.
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What is glomerular filtration rate?
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The volume of fluid filtered from the glomeruli into Bowman's space per UNIT time.
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What is the GFR regulated by?
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Net filtration pressure
Membrane permeability Surface area available for filtration |
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What is the normal GFR of a 70 kg individual?
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180L/ day or 125mL/min
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What happens to the GFR when we are sick?
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When we are sick, glomeruli are lost and the surface area decreases, thus decreasing GFR.
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What is the plasma volume of a normal individual?
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3.5 L
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How many times per day is plasma filtered at the glomeruli?
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51 times per day. (180L filtered per day, volume of plasma is 3.5L, 180/3.5=51.)
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What are two ways you can increase GFR?
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You can constrict the efferent arteriole by renin
You can dilate the afferent arteriole, allowing more blood to go through (by prostaglandin) |
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What are two ways you can decrease GFR?
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You can dilate the efferent arteriole and
constrict the afferent areteriole (not allowing blood to flow through) |
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How does GFR compensate for pressure fluctuations in the glomerulus?
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If the pressure decreases, less fluid is filtered into Bowman's space (GFR decreases). If less fluid is filtered, the pressure can go back up
If pressure is too high, more fluid is filtered (GFR increases) and therefore the increased fluid leaving the capillaries can decrease the pressure back to normal. |
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What is the filtered load?
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Total amount of any freely filtered substance
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How do you calculate filtered load?
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GFR x plasma concentration of the substance
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What is the filtered load of glucose?
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180g/day
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How is net absorption defined?
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If the filtered load is GREATER than the amount of the substance excreted in the urine.
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How is net secretion defined?
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If the filtered load is LESS THAN the amount excreted in the urine: net secretion. This means that along the tubule segments more of the substance was released into the lumen.
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What does the GFR have to be in order to excrete waste products adequately?
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LARGE
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If the GFR is large, what does this mean for the filtered volume of water and filtered loads of all nonwaste plasma solutes?
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They must also be LARGE
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What is the role of the proximal tubules?
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Reabsorbs most of the FILTERED WATER and SOLUTES.
Major site of SECRETION of various solutes, except K+ |
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What is the role of the loops of Henle?
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Reabsorbs large quanities of major ions, and some water.
It does this by using the countercurrent multiplier system to generate a concentration gradient in the interstitium. This results in concentrated urine. |
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What is the role of the distal convoluted tubule and the collecting duct?
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It is responsible for FINE TUNING.
It determines the final amounts excreted in urine by mostly regulating rates of reabsorption (some secretion) SIte of homeostatic control |
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What are two ways that substances can be absorbed when passing from the tubular lumen to the pertitubular capillary?
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The substances can pass through TUBULAR EPITHELIAL CELLS in two ways.
1) either through tight junctions, into the ISF and back to the peritubular capillaries 2) Through the luminal membrane through the tubular epithelial cell, through the BASOLATERAL membrane, into the ISF and then into the peritubular capillaries. |
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What is urea?
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A waste product of protein metabolism
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Why are filtered loads generally alot larger than the amount of the actual substance in the body?
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The substance is recirculated in the blood
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What type of reabsorption is that of waste products?
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INCOMPLETE
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What type of reabsorption is that of the most useful plasma components?
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COMPLETE (relatively)
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What substance reabsorption is HIGHLY regulated?
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Water, inorganic ions
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What type of substance reabsorption is NOT regulated?
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Glucose, amino acids
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What is diffusion?
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The movement through tight junctions connecting tubular epithelial cells. There is no need for energy as the substance moves along its gradient from high concentration to low.
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How is urea reabsorbed?
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At the proximal tubule, water reabsorption occurs. Urea concentration then becomes high. Urea diffuses into the interstitial fluid and peritubular capillaries.
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How does mediated transport in reabsorption occur?
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Reabsorption by mediated transport occurs across tubular cells in a process known as TRANSCELLULAR EPETHELIAL TRANSPORT.
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What does transcellular epithelial transport require?
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The participation of TRANSPORT proteins in the plasma membrane of the tubular cell.
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What are the transport proteins usually coupled to?
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Reabsorption of sodium
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How is glucose transported from the tubular lumen to the peritubular capillaries?
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The Na+/K+ pump on the basolateral membrane side functions to push Na+ out of the tubular epithelial cell into the ISF. This decreases the Na concentration inside the cell. So sodium inside the tubular lumen will move along its CONCENTRATION GRADIENT into the tubular epithelial cell. The sodium transporter on the luminal membrane side acts as a COTRANSPORTER/ SYMPORTER for glucose, allowing it to move into the tubular epitheliel cell with sodium. Glucose transporters on the basolateral membrane side allow glucose and aa's, etc to move into the ISF.
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What are the two ways to classify mechanisms of solute transport?
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Passive and active
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What is passive transport?
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Spontaneous, down an electrochemical gradient. It does NOT require energy.
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What are some examples of passive transport?
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Diffusion, facilitated diffusion, and by solvent drag.
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What are some examples of facilitated diffusion?
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Through channels, uniporters, or by coupled transport (antiporter or symporter)
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What is solvent drag?
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When water moves from lumen to interstium, it drags urea with it.
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What is active transport?
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It is transport against an electrochemical gradient, and therefore requires the INPUT of energy.
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What is mediated transport?
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Facilitated diffusion and active transport.
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What is Tm?
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Transport maximum!
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What is transport maximum?
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When a tubule cannot reabsorb a substance any more. THis occurs when the membrane transport proteins have become saturated.
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How can Tm be reached?
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The filtered load is very high.
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How does Tm correlate in diabetes?
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Too much glucose, and the transporters cannot work to reabsorb all of it. As a result, glucose is excreted in the urine. This results in glucosuruia.
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What is tubular secretion?
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Movement of substances from the peritubular capillaries into the tubular lumen. It is the opposite of reabsorption
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What is tubular secretion mediated by?
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Diffusion and transcellular mediated transport.
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What are the most important substances secreted by the tubules?
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Hydrogen ion and potassium.
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What is tubular secretion normally coupled to?
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Reabsorption of sodium
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What is clearance?
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The VOLUME of PLASMA from which the substance is completely removed, ie. cleared, per unit time. Ie. how fast plasma can be cleared.
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How do you calculate clearance?
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Clearance= Mass of S excreted per unit time/ Plasma concentration of S
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How do you calculate the Mass of a substance excreted per unit time?
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Urine concentration of S x Urine volume per unit time
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What is inulin?
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A polysaccharide produced and purifed from beets. IIt is not produced by animals and administered intravenously.
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How is inulin clearance the most accurate marker of GFR?
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It is FREELY filtered at the glomeruls, but is not REABSORBED, SECRETED, or METABOLIZED by the tubule. Thus, the clearance of inulin is equal to the GFR.
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What is creatinine?
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A waste product produced by the muscle
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Why is creatine used as a clinical marker for GFR?
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It is filtered freely at the glomerulus and is NOT reabsorbed. It is secreted at the tubule but the amount is small. It is NOT metabolized by the tubule.
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Why would someone lose their GFR?
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Kidney damage, process of developing kidney failure, loss of hormones
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How does clearance and GFR compare in SECRETION?
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If the clearance of a substance is higher than GFR, it is secreted at the tubule.
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How do clearance and GFR compare in REABSORPTION?
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If the clearance of the substance is less than GFR, it is reabsorbed at the tubule.
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What is para-amino-hippurate a marker of?
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Renal plasma flow. There is a net secretion.
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What is sodium and water critical for?
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Blood pressure, volume, and maintenance of life
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How do the levels of sodium and water stay in the body? How does this compare with intake of fluid?
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Body salt and water remain CONSTANT despite a VARIABLE intake.
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How does the intake of water and sodium compare to its output?
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Water and sodium intake equals their output
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What is the range of water output per day?
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0.4-25L
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What is the range of NaCl output?
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0.05 to 25g
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What are some ways one can GAIN water?
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Through liquids, food and as a metabolic side product
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What are some ways someone can LOSE water?
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Insensible loss in the skin and lungs
Sweat In feces Urine |
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How is sodium GAINED?
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Through ingestion of FOOD
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How is sodium LOST from the body? What is the main way?
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Sodium can be lost in SWEAT, FECES, and URINE
The majority of sodium is lost in the urine |
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Where is sodium reabsorbed? How is this reabsorption distributed?
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67% Proximal Tubule
25% Thick ascending limb of the loop of Henle 4% in the Distal Tubule 3% Cortical Collecting Duct 1% is lost in the urine |
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Where is the only place in the tubular segments that sodium reabsorption does NOT occur?
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The thin descending limb of the loop of Henle
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What type of process is sodium reabsorption?
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It is active, and therefore uses ATP
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What type of reabsorption is water and what is it dependent on?
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Water reabsorption is by DIFFUSION and therefore is not active and does NOT require energy.
It is dependent on SODIUM REABSORPTION |
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What is the inside of the renal tubule referred to?
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The apical or urine side
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What is the outside of the renal tubule refererd to?
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The basolateral or blood side
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What does it mean for the tubular cells to be polarized?
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One side does one thing, the other does another.
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What are the three mechanisms for sodium transport in the PROXIMAL TUBULE?
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Na/H+ antiporter, Na/glucose-cotransporter, Na-amino acid cotransporter
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What is the mechanism for sodium transport in the Cortical Collecting Duct?
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Diffusion via Na+ channels
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How does water move out of the cell into the interstitium?
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The water moves passively through AQUAPORINS into the interstistium and towards the blood.
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What does the Proximal Tubule do?
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Reabsorbs the BULK of filtered small solutes.
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What % of filtered substances does the proximal tubule reabsorb?
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60% filtered NaCl, K, Ca
More than 90% of filtered bicarbonate (HCO3) 100% glucose and aa reabsorption by Na-dependent cotransport |
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What exchanger is present in the LATE PROXIMAL TUBULE?
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Na+/H+
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Where does secretion of toxins and drugs occur?
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Terminal portion of the Proximal tubule- they are ELIMINATED
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How is sodium transported in the THICK ASCENDING LIMB of the loop of HENLE?
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Na-K-2Cl-cotransporter
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How is sodium reabsorbed in the distal convoluted tubule?
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Na/CL cotransporter
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What do changes in total body Na result in?
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Changes in ECF volume in the interstitium and the vascular space
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What is total body Na sensed as?
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VOLUME- intravascular filling by the baroreceptors
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How does plasma sodium concentration correlate with total body sodium?
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It does not correlate at all, sodium plasma concentration stays constant even if intake varies
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What does plasma sodium reflect?
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The relative relationship between total body Na and water
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What happens if you have a high total body Na?
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The accompanying water will also be high, and therefore will result in high ECF volume and plasma volume.
Plasma concentration of sodium is constant |
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What happens if you have a low total body sodium?
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This means that the accompanying water volume is low, resulting in a low ECF volume and plasma volume.
Plasma concentration of sodium is CONSTANT |
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What are the four main regulatory systems of volume?
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Sympathetic nervous system
Renin-angiotensin-aldosterone system Atrial naturetic peptide Vasopressin (ADH) |
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How do the volume regulatory systems regulate volume?
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They change their activity in response to changes in body fluid volume.
They do so by varying Na and water handling in the kidney. |
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How does the sympathetic system regulate volume?
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Low total body sodium=low plasma volume= low BP
Baroreceptors sense this low BP and intiate SYMPATHETIC reflexes. They constrict the renal arterioles to lower GFR (glomerular filtration rate) Tubules increase Na absorption |
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What is the point of the RAS system?
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Keep blood flow coming to the kidney
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What is renin?
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An enzyme released from granular cells in the wall of the renal afferent arterioles.
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What does renin do?
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Cleaves angiotensinogen into angiotensin I
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What does ACE (angiotensin converting enzyme) do?
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Converts angiotensin 1 to angiotensin 2
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What does angiotensin 2 do?
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Promotes salt retention, enhances Na reabsorption in the proximal tubule and stimulates production and release of aldosterone
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What is aldosterone?
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A STEROID hormone produced by the adrenal gland
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What does aldosterone do?
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It stimulates SODIUM REABSORPTION in the DCT and CCD
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What happens when you don't have ANY aldosterone?
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2% of the filtered load is excreted (35g of NaCL)
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What happens when you have high levels of aldosterone?
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0% of the filtered load is excreted, sodium is completely reabsorbed
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Where is the adrenal gland located?
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It sits on top of the kidney(s)
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What are the components of the adrenal gland?
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Capsule (Zona glomerulosa, zona fasculata, zona reticularis) and medulla (inside).
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What does the adrenal gland produce?
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Aldosterone
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Where does aldosterone act?
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Aldosterone goes into the nucleus of the CCD cells and acts on Na+/K+ ATPase and Na+ channels and K+ channels to upregulate their expression and consequently their activity is increased
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What is tubuloglomerular feedback?
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A way the tubule reports on volume state
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What is the juxtaglomerular apparatus?
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It is made of MACULA DENSA.
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What is the macula densa composed of?
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Plaque of DISTAL TUBULAR CELLS adherent to the arterioles and the renin-containing JUXTAGLOMERULAR GRANULAR CELLS (on the arteriole)
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How does the MACULA DENSA provide feedback?
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It "tastes" the fluid. if the Na concentration is low, it means glomerular blood flow is low. It informs the ARTERIOLE which in turn releases RENIN
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What does ANP stand for?
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Atrial natriuretic peptide
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What is atrial natriuretic peptide?
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A peptide HORMONE secreted by the cells in the CARDIAC ATRIA when they are stretched (HIGH VOLUME STATE)
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What does ANP do?
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Acts on tubules to INHIBIT sodium reabsorption
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What stimulates ANP secretion?
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Increased total body sodium (also means increased ECF fluid volume and increased plasma volume)
The body wants to get rid of this excess volume and therefore needs to get rid of salt because SALT=VOLUME |
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What is pressure natriuresis?
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Increased blood pressure increases SODIUM EXCRETION
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What is osmolarity?
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It is the total solute concentration of a solution.
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What is osmolarity a measure of?
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Water concentration: ie. the higher the solution osmolarity, the lower the water concentration
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What is the normal osmolarity of blood?
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300 mOsm.
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What does hypoosmotic mean?
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Having total solute concentration less than that of normal ECF fluid, ie. less than 300mOsm
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What does isoosmotic mean?
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Having a total solute concentration equal to that of normal ECF
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How much water is reabsorbed?
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99%
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Where does the majority (2/3) of water reabsorption take place?
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Proximal tubule
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What is the first step in water reabsorption?
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Na is pumped actively from proximal tubular cell to the blood
Na is reabsorbed from the tubular lumen to the ISF across the cells |
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What happens to the osmolarity of the lumen and the interstitium when sodium is reabsorbed from the lumen of the tubules?
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The local osmolarity decreases in the LUMEN
The local osmolarity increases in the interstitium |
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What does the difference in osmolarity between the lumen of the tubules and the interstium cause?
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Water to follow from the tubule into the interstitial fluid through tubular cells' plasma membrane through tight junctions.
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How does everything move from the interstitium to the peritubular capillaries?
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Interstitial pressure drives BULK FLOW
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What happens when water intake is SMALL?
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Kidney absorbs more water, urine output decreases
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What happens when water intake is LARGE?
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Kidney reabsorbs LESS water, urine output is LARGE
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Where does water regulation take place?
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In the collecting duct
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What are two critical components of water regulation by the collecting duct?
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Permeability of collecting duct to water
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What regulates the permeability of the collecting duct to water?
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ADH/Vasopressin
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What are the two components to DISTAL TUBULE water regulation?
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1.Generate a high osmotic gradient in the interstitium.
2. They are the site of ADH action and insertion of aquaporin-water channels so that the water can be reabsorbed |
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How is the loop of Henle positioned in most nephrons?
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Normally, the loop of henle is short and located in the CORTEX
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What are MEDULLARY NEPHRONS, and how many of the total nephrons are these?
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The loop of Henle is LONG and goes into the medulla of the kidney. 20% of nephrons are these.
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Which type of nephrons generate the osmotic gradient?
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The medullary nephrons
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How is urine concentrated?
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By the countercurrent multiplier system
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Up to how high can the urine be concentrated by the kidney?
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1400 mOsm
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Where does concentration take place?
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Medullary collecting ducts
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What does urinary concentration depend on?
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The hyperosmolarity of the interstitial fluid
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What happens in the presence of vasopressin?
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Water leaves the tubule and diffuses out into the interstitial fluid in the medulla to be carried back to the blood
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How does the medullary interstitial fluid become hyperosmotic?
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The countercurrent multiplier system
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What does "countercurrent flow" refer to?
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The opposing flow of fluid,
DOWN in descending limb UP in ascending limb |
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What would happen without vaspopressin?
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You would have very dilute urine
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What happens when you are nauseous?
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Nausea is a potent stimulus for ADH release. Kidney stars reabsorbing right away in anticipation of the sudden loss in body volume.
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What happens when you severely sweat?
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Lose hypoosmotic fluid, water leaving is greater than Na leaving.
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What does the loss of hypoosmotic salt solution cause?
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A lower plasma volume and higher plasma osmolarity.
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What happens to the GFR when plasma volume decreases?
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GFR decreases
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What happens when GFR decreases?
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Sodium excretion decreases
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What also happens when plasma volume decreases?
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Plasma aldosterone increases, also resulting in decreased sodium excretion.
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What does increases plasma osmolarity result in?
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Increased plasma vasopressin
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What does increased vasopressin result in?
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Decreased water EXCRETION, due to increased water REABSORPTION
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What is the thin decending limb of the loop of henle permeable to and impermeable to?
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Permeable to water, impermeable to Na
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What is the ascending limb of the loop of Henle impermeable/permeable to?
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Impermeable to H2O and permeable to Na.
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Where is the Na-K-2Cl co transporter located?
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On the ascending limb of the loop of Henle
It brings other essential ions K+ and Cl- back into the circulation, as well as allows sodium to enter the tubular cells. |
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What is the vasa recta?
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The blood vessels in the medulla of the kidney. It supplies blood to the medulla.
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What does the vasa recta do?
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Prevents osmolarity from being dissipated
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What does the U shape of the vasa recta permit?
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Bulk flow of fluid and solutes into the blood via colloid osmotic (due to blood proteins) and hydrostatic pressure, that favors reabsorption.
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How much solute and water does the vasa recta carry away?
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Only as much as the NET ABSORBED from the medullary tubules so it maintains the high concentration established by the countercurrent mechanism- interstitium is in a STEADY STATE.
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What does water reabsorption depend on?
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Water permeability of the tubule
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What does permeability depend on?
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Presence of water channels- AQUAPORINS
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What is water permeability regulated by?
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The amount of aquaporins in the plasma membrane
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Where is vasopressin the key hormone?
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In the collecting duct
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How is vasopressin released?
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Osmoreceptors in the hypothalamus are stimulated when osmolarity exceeds 300mOsm.
This tells the brain "Im thirsty" Neurons of the hypothalamus terminate in the posterior pituitary. ADH is released ADH acts on the kidney. |
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What is the effect of vasopressin action on the kidney?
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Permeability. Water channels are inserted and water stays in the blood stream, and urine is concentrated
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What is vasopressin?
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Peptide hormone, ADH
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Where is vasopressin released?
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In the posterior lobe of the pituitary gland
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What type of receptor does vasopressin couple to?
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V2 receptors in the kidney
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What side of the tubular cells does vasopressin stimulate the insertion of aquaporins?
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The luminal membrane (urine side) of the collecting duct cells
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What is water diuresis?
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When vasopressin is NOT present, collecting ducts become impermeable to water- water diuresis. Increased urine volume
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What is diabetes insipidus?
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A disease state caused by the malfunction of the vasopressin system. Either vasopressin is not released by the pituitary or there is no receptor in the tubule cell)
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What is the most abundant INTRACELLULAR ion?
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Potassium-
98% intracellular fluid 2% Extracellular fluid |
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What is the potassium concentration in the ECF important for?
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Function of excitable tissues (nerve and muscle)
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Why is the potassium so important for function if excitable tissues?
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The resting membrane potentials of these tissues are directly related to the relative intracellular and extracellular K concentrations.
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What is hyperkalemia?
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High concentration of K in the ECF. (ie. above 5mEq/L)
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What is hypokalemia?
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Low concentration of K in the ECF (ie. lower than 3.5mEq/L)
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What can both K level abnormalities cause?
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Abnormal rhythms of the heart and abnormalities of skeletal muscle contraction
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What is the effect of hyperkalemia on the electrocardiogram- pre cardiac arrest?
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The cells feel partially depolarized. In cardiac arrest, cells are depolarized so the heart cannot contract normally.
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What is depolarization?
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Potassium rushes out of the cell, causing the membrane potential to get more positive.
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What happens with low potassium and contraction of the heart?
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Body weakens and it is harder for the cells to depolarize, and therefore harder for them to contract.
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What is potassium balance maintained by?
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The kidney
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Out of the dietary intake of potassium, how much is excreted into the urine?
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90%
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Out of the dietary intake of potassium, how much is excreted into the feces/sweat?
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10%
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What happens to potassium at the glomerulus?
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Potassium is freely filtered at the glomerulus
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What happens to potassium normally in the tubules?
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Potassium is normally reabsorbed in the tubules and therefore little of the FILTERED POTASSIUM appears in the urine.
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What is different about potassium from sodium and water vis a vis the collecting duct?
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Potassium can be secreted at the cortical collecting ducts.
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What are changes in potassium excretion due to?
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Changes in Potassium SECRETION at the CCD (and some in the Distal tubule)
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What hormone is responsible for K+ secretion?
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Aldosterone
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What is aldosterone?
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It is a TRANSCRIPTIONAL REGULATOR. It goes into the nucleus of the principal cells of the COLLECTING DUCT.
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What does aldosterone do?
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It causes more Na and K channels to be made.
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What is a consequence of the increased levels of Na and K channels due to aldosterone?
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More Na is resorbed and more K+ can therefore leave passively from the blood and enter the tubule + urine.
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What is potassium secretion regulated by?
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Dietary intake of potassium
Aldosterone Distal tubular flow of urine |
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How does distal tubular flow of urine regulate K+?
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The more Na going past in the Na channels, the more K+ comes out in the urine.
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How does regulation of potassium occur with dietary intake/aldosterone together?
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When potassium intake increases, this results in an increase in plasma potassium.
This stimulates the adrenal cortex to secrete more aldosterone |
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What does aldosterone do?
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Acts on the CCD to increase potassium secretion (going from blood to urine) and potassium is therefore excreted.
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What can also cause an increase in potassium secretion besides increased potassium in the plasma?
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A decrease plasma volume can activate the RAS system and cause an increase in the level of angiotensin II. This causes aldosterone secretion from the adrenal cortex which ultimately leads to increased potassium secretion.
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What is hyperaldosteronism?
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The conditions in which the adrenal hormone aldosterone is released in excess.
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What is the most common cause of hyperaldosteronism?
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An adenoma, little tumor, of the adrenal gland that produces aldosterone autonomously.
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What are some consequences of hyperaldosteronism?
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Increased fluid volume (Na retention), hypertension, hypokalemia. Renin is suppressed. Metabolic alkalosis.
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What are metabolic reactions highly sensitive to?
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The hydrogen ion concentration in the environment.
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What is the normal pH of the ECF?
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7.4 with a H+ concentration of 40nmol/L
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What is the lower limit for life of pH?
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6.8
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What is the upper limit for life of pH?
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8.0
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What happens beyond the pH limits for life?
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Enzymes in the body can't work. For example, too much acid causes a denaturation of proteins. If enzymes can't work, they cannot catalyze crucial cell reactions. This leads to DEATH!
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What does carbonic anhydrase do?
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It is the enzyme for the reaction of the conversion of CARBON DIOXIDE and WATER to carbonic acid.
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What does carbonic acid dissociate into?
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H+ and HCO3- (bicarbonate)
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When a bicarbonate ion is lost from the body, it is the same thing as if...?
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It is the same as if the body gained a hydrogen ion.
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What are some ways one can GAIN hydrogen ions?
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Generation of H+ ions from CO2.
Production of NONVOLATILE acids from the metabolism. Gain of H ions due to loss of bicarb in diarrhea,etc.. Gain of H ions due to loss of bicarb in the urine |
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How can someone LOSE H ions?
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Using H ions in metabolism
Loss of hydrogen ions in vomitus. Loss of H ions in urine Hyperventilation (loss of CO2) |
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What is NOT a nonvolatile acid?
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H2CO3
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What happens in hyperventillation?
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The increased rate of breathing OUT Co2 removes it from the blood, thus decreasing blood and consequently ECF acid concentration.
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What are some nonvolatile acids?
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Phosphoric acid
Sulfuric acid Lactic acid |
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What is the average net production of nonvolatile acids?
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40-80 mmol of H+ per day
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How do we get rid of the net production of nonvolatile acids?
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We breath them off, or the kidneys get rid of it, or we MAKE HCO3- to buffer the acid.
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What is a buffer?
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A substance that can reversibly bind H ions.
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How do you calculate pH?
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-log(H+ concentration)
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What is the "buffering formula"?
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Buffer + H+-> H buffer
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What is the major extracellular (ie. in the blood) buffer?
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The Co2/HCo3- system
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What are the major intracellular buffers?
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phosphates and proteins
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Does buffering eliminate H+ from the body?
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No. It only keeps them occupied
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What is the ultimate balance of hydrogen ion controlled by?
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The respiratory system and the kidneys
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How does the respiratory system control the balance of H+ ion?
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It controls levels of carbon dioxide
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How do the kidneys control the balance of H+ ions?
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It controls the levels of bicarbonate
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What is the renal mechanism for when there is a low H+ concentration?
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Kidneys excrete HCO3- (there is TOO much buffer in this case)
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What is the condition called for low pH?
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Acidosis, (High H+ concentration)
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What is the condition called for high pH?
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Alkalosis (low H+ concentration)
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What is the renal mechanism for when there is a high H+ concentration?
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Kidneys produce NEW bicarbonate and add it to the plasma. Its like you are getting rid of H+ ions.
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What is the Henderson-Hasselbach equation?
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pH= 6.1 + log [HCO3-]/[CO2]
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What does the Henderson-Hasselbach equation tell us?
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The constant pH depends on a ratio between the two buffer components.
If bicarbonate decreases, carbondioxide concentration would also have to decrease to keep the ratio the same. |
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Why can't the bicarbonate ions that are filtered by the glomerulus be directly reabsorbed?
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Bicarbonate ions do not readily penetrate the membrane.
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How are bicarbonate ions indirectly reabsorbed?
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They combine with H+ to form H2CO3. This eventually becomes CO2 and H2O. The CO2 can move easily across the tubular membrane.
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What is the renal handling of bicarbonate also mediated by?
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H+/K+ ATPase
and the Na+/H+ antiporter which push the H+ to the urine |
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Where does the majority of HCO3 reabsorption take place?
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80% in the proximal tubule
15% in the thick ascending limb of the loop of Henle. 5% in the distal tubule |
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How much bicarbonate is usually in the urine?
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Very little, none
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How is addition of new bicarbonate acheived?
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By H+ secretion and excretion of non-bicarbonate buffers, ie. phosphate, to the urine
By glutamine metabolism with NH4 (ammonia) excretion |
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Why are both processes of "new bicarbonate" like H+ excretion by the kidneys?
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H+ goes to the urine side and HCO3- goes to the blood side.
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How do the kidneys compensate for the generation of nonvolatile acids in the body?
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They contribute enough new HCo3
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How do we decrease the acidity of the urine once all the bicarbonate has been reabsorbed and is no longer available in the urine?
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H-phosphate catches the H+ as they are leaving and forms H2PO4. It is in this form that acid is excreted
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How is filtered glutamine allowed to enter the proximal tubular cells?
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The filtered glutamine is cotransported along with Na into the cell.
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What does glutamine break down into?
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Bicarbonate and ammonium
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What happens to the ammonium generated from glutamine?
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It leaves the cell along with sodium ANTIPORTERS and combines with H+ in the urine and is excreted
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What does respiratory ALKALOSIS arise from?
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Increased respiration and blowing off Co2
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What does metabolic alkalosis result from?
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Bicarbonate ingestion with renal failure, etc...very rare!
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What does respiratory acidosis result from?
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Decreased respiration and a rise in CO2
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What does respiratory acidosis result from?
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Decreased respiration and a rise in CO2.
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What does metabolic acidosis result from?
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Lactic acidosis, (like in exercise) aspirin overdose.
Acidosis can also arise from vomiting, because you are losing gastric contents which are high in H+ |
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What are the renal responses to acidosis?
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-Reabsorbs filtered HCO3
-Even more H+ is secreted, but they leave with H-PO4, so it is like you are adding new HCO3 to the plasma -Enhances tubular glutamine metabolism, which creates HCO3, and ammonium excretion is enhanced. Since ammonium takes away H+ this also contributes new bicarb to the plasma. |
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What is the net result of renal responses to acidosis?
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More new HCO3 than usual is added to the plasma. This compensates for the acidosis
The acid moves from the blood to the urine |
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What is the renal responses to alkalosis?
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-Rate of H+ is too low, cannot combine with all HCO3, so HCO3- is EXCRETED
-There is no secretion of non- HCO3 buffers -Decrease of tubular glutamine metabolism |
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What is the net result of the renal response to alkalosis?
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Plasma HCO3 decreases, thereby compensating for the alkalosis.
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How do the levels of H+, HCO3-, and CO2 fluctuate in Respiratory acidosis?
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H+ increases, HCO3- increases, and CO2 increases.
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Why does the HCO3- change in respiratory acidosis/alkalosis?
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It is part of renal compensation (in order to keep CO2/HCO3- level ratio constant to keep pH constant)
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Why does the CO2 levels change in metabolic acidosis/alkalosis?
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It is part of the ventilatory compensation, in order to keep the CO2/HCO3- level ratio constant to keep pH constant)
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Why do bicarbonate levels INCREASE in respiratory acidosis but DECREASE in metabolic acidosis?
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In respiratory acidosis, biacarbonate increases in order to keep the HCO3/CO2 ratio constant.
In metabolic acidosis, HCO3 buffers the acid, and therefore its level decreases. |
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What are diuretics?
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Drugs that are used clinically to increase the volume of urine excreted.
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What do diuretics do?
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They act on the tubules to inhibit the reabsorption of sodium. This changes the "volume status". IT also inhibits chloride and sometimes bicarbonate, resulting in increased excretion of all these substances, and water as well.
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What is furosemide?
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It is a diuteric that is used to get rid of excess volume.
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What is hypochlorothiazide?
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It is a diuretic used to control blood pressure. If you increase blood pressure, you increase the blood volume and in turn increase sodium.
Therefore you get rid of more sodium and therefore more water. |
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What do loop diuretics act on?
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The thick ascending limb of the loop of Henle
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What do loop diuretics inhibit?
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Sodium-K-CL co transporter
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What is an example of a loop diuretic? Are they commonly used?
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Furosemide is an example of a loop diuretic.
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What is a side effect of using loop diuretics?
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It lowers potassium in the plasma due to increased distal flow of sodium. ( Sodium reabsorption causes K+ usually to flow out of the tubular cells into the interstitium)
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What is the net effect of Loop diuretics?
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Increased sodium excretion, and therefore an increase in urine volume?
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What do thiazides do?
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BLock the Na-CL co transporter in the distal convoluted tubule
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What is different about POTASSIUM-SPARING diuretics?
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Plasma concentration of potassium does not decrease
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Why doesn't plasma potassium levels decrease in potassium-sparing diuertics?
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It inhibits Na reabsorption as WELL as inhibits K+ secretion (moving from blood to urine).
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How do potassium diuretics act?
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THey block the action of aldosterone
Block epithelial Na channel in the CCD |
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What is amiloride?
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A potassium-sparing diuretic that blocks the Na channel
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What is spironolactone?
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It competes with aldosterone, therefore decreasing the full potenial of aldosterone
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What happens when aldosterone function is reduced?
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It cannot creaet sodium channels on the tubular lumen side or sodium/K+ atp ases on the basolateral side.
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What type of diuertic is the collecting duct diuretic?
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K+ sparing
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What can happen to an individual who takes K sparing diuretics?
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They can become hyperkalemic
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Why would one clinically use diuretics?
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If the renal system retained too much salt and water, resulting in an expansion of the ECF (edema)
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Why would you use a diuretic in congestive heart failure?
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Cardiac failure leads to a lower cardiac output. Fluid is "stuck" somewhere. You would want to use diuretics to get rid of this congestion.
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Why would you use a diuretic in hypertension?
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Retained salt and water contributes to the high blood pressure.
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What is proteinuria?
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A common feature of kidney failure. Protein is in the urine, the glomerulus is no longer able to keep the proteins.
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Why would hypocalcemia result from kidney failure?
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Decreased secretion of 1,25-vitamin D which is responsible for calcium levels
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Why would anemia result from kidney faiilure?
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Decreased secretion of eryrhtropoetin
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What are some consequences of kidney failure?
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Accumulation of waste products (urea, creatinine, phosphate, sulfate)
High K+ concentration in blood (misfiring of cells) Metabolic acidosis |
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On how many nephrons can a person survive?
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10%
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What are some types of renal replacement therapy?
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Hemodialysis- blood cleaning replacement
Peritoneal dialysis- replaces kidney Kidney transplantation |
