Ch. 17 Day 2 Flashcards
Clearance
Net amount that is lost/excreted
Volume of plasma from which a given substance is cleared by the kidneys per unit time
Every substance in the blood has own distinct clearance values; units expressed as volume of plasma per unit time, e.g. mL/min or L/day
Clearance Equation (**KNOW FOR EXAM)
((mass of x in urine) * ( urine volume/time))/plasma concentration of x
Ex: (18.2mg/mL)(1 mL/min)/0.26 mg/mL = 70 mL/min
Know how to work this equation…and know units
The concept of clearance can be used to calculate GFR, assuming you use a substance that is?
- Freely filterable at the glomerulus (so that its concentration in glomerular filtrate is the same as in plasma)
- Not secreted by tubules
- Not reabsorbed by tubules
Such a substance is the polysaccharide INULIN
–do NOT confuse that with insulin
Use of clearance of inulin to calculate GFR
If mass excreted/time = mass filtered/time, then:
GFR = C(inulin) = (U(inulin))(V)/P(inulin)
- Infuse in inulin into a subject such that its plasma concentration is 4 mg/mL
- Collect using for 2 hours, collected 0.2L
- Measure urine inulin concentration: 360 mg/mL
What is GFR?
(360 mg/mL)(0.2L/0.2 h)/4 mg/L = 18L/2h = 9L/h = 150 mL/min
If inulin were secreted, would the calculated GFR be higher or lower than the true GFR? Why?
Higher b/c it’s secretion
If inulin were absorbed, GFR would be lower
Glucose is freely filtered at the glomerulus, but it is also totally reabsorbed in the proximal tubules and returned to plasma. What is the clearance of glucose?
Zero return on glucose, because it’s returned to plasma
Reabsorption
Recall that GFR = 180L/day and total body water = 40L. Thus almost all of that 180L (99%) must be returned to circulation via reabsorption in tubular epithelium
–filtration is nonselective (except for protein); reabsorption is highly selective
What is reabsorbed?
Water
Electrolytes (ions) - Na+, K+, Cl-, HCO3-, H+, Ca2+, PO4(^3)-
Small organic molecules - glucose, AAs, etc.
Is water reabsorbed via active transport or passively?
Passively!!
Water is always reabsorbed passively (by osmosis), there is NOT ACTIVE TRANSPORT OF WATER
General pathway for reabsorption
Tubule –> epithelial cells –> interstitial –> peritubular capillaries
When it comes to the following substances, which one is incompletely reabsorbed? Why?
water
sodium
glucose
urea
Urea is incompletely reabsorbed, so we tend to lose it from the body.
It’s how the body disposes/excretes excess nitrogen
When it comes to the following substances, which one(s) are highly reabsorbed (99% and up reabsorption rate)?
water
sodium
glucose
urea
Water (99%), sodium (99.5%), glucose (1005)
Tubular reabsorption of some substances cannot be physiologically controlled.
Ex: glucose filtered = 180g/day, glucose excreted = 0g/day
Tubular capacity for reabsorption of glucose > GFR, so reabsorption of glucose is always maximal
Therefore, reabsorption of glucose is NOT adjusted or altered
Reabsorption of H2O and Na+ can be altered under normal conditions
Ex: ingested water will be excreted into urine w/in a few hours
Therefore, there is a control mechanism which acts to maintain plasma water w/in fairly narrow limits
What are the methods of reabsorption?
Epithelial transport (transcellular transport)
Paracellular transport
Epithelial transport (transcellular transport)
Substances cross apical and basolateral membranes of tubule epithelial cells
Apical side faces fluid
Paracellular pathway
Substances pass through the cell-cell junction between 2 adjacent cells
–includes small anions, water…
Is there low or high hydrostatic pressure in peritubular capillaries? What does this favor?
Lower hydrostatic pressure in peritubular capillaries
Favors the movement of fluid and solutes into those capillaries instead of out of them
In general, whatever happens to Na+ will also happen to ____.
Water
Reabsorption: Na+ Cotransport
aka Secondary Transport
Carrier SGLT1 will not bring Na+ in unless it’s also bringing in a glucose (and vice versa); this allows both of these things to be reabsorbed
Reabsorption of Glucose
Glucose/Na+ cotransporters have a transport maximum (Tm)
- -a) if there is too much glucose in filtrate, it won’t be completely reabsorbed b/c all carriers are in use (saturated)
- -b) extra glucose spills over into urine = glycosuria and is a sign of diabetes mellitus
- -c) extra glucose in the blood also results in decreased water reabsorption and possible dehydration
In the Proximal Tubule, what percentage of water and Na+ is filtered?
65%
Descending limb is highly permeable to ____, and somewhat permeable to?
Highly permeable to water
Somewhat permeable to ions, Na+, and urea
Thick ascending limb is impermeable to ____, which is important for?
Impermeable to water, important for kidney ability to concentrate urine
In the collecting duct, the ability to reabsorb ____ is possible, but completely dependent on?
Ability to reabsorb water is possible, but completely dependent on hormone control (ADH, aldosterone)
Summary of tubular transport
- Water transport entirely via PASSIVE DIFFUSION
- As progress through tubular system, volume of tubular fluid decreases due to reabsorption of water
- -progressively concentrating the urine - Avid reabsorption of substances of nutritional significance (glucose, AA, etc.) takes place via secondary active transport in proximal tubules
- Reabsorption of metabolic wastes (urea, creatinine) poor or nonexistent
- Reabsorption of electrolytes (sodium, potassium) by tubules is under physiological control and can be altered under different conditions
Kidneys control osmolality
Osmolality = solute concentration
Kidneys control osmolality of body fluids by excreting either a concentrated (greater proportion of solutes) or dilute (greater proportion of water) urine
The major determinant of plasma osmolality is ____.
Na+
Therefore (Osm)plasma is a function of [Na+]plasma
When (Na+)plasma increases, (Osm)plasma increases
Increase in (Osm)plasma
Kidney conserves water (reabsorbs more water than solutes) –> restores (Osm)plasma
Decrease in (Osm)plasma
Kidney excretes water (reabsorbs more solutes than water) –> restores (Osm)plasma
Collecting Duct and ADH
- Last stop in urine formation
- Impermeable to NaCl but permeable to water
- -a) also influenced by hypertonicity of interstitial space - water will leave via osmosis if able to
- -b) permeability to water depends on the number of aquaporin channels in the cells of the collecting duct
- -c) availability of aquaporins determined by ADH - ADH binds to receptors on collecting duct cell s–> cAMP –> protein kinase –> vesicles w/ aquaporin channels fuse to plasma membrane (water channels removed w/o ADH)
- ADH produced by neurons in hypothalamus but stored and released from posterior pituitary gland - release stimulated by increase in plasma osmolality
Excreting Concentrated Urine
increase in (Osm)plasma –> osmoreceptors send nerve signals –> posterior pituitary secretes ADH –> medullary collecting duct –> insertion of aquaporin into epithelium –> increased water reabsorption –> concentrated urine (conserves water)
Excreting Dilute Urine
decrease in (Osm)plasma –> osmoreceptors (NO nerve signal) –> posterior pituitary (NO ADH release) –> medullary collecting duct –> NO insertion of water pores into aquaporin –> decreased water reabsorption –> dilute urine (excretes water)
Summary of Effects of ADH on Urinary Excretion
Increase in ADH –> water reabsorbed –> concentrated urine
Decrease in ADH –> water excreted –> dilute urine
Excretion of concentrated urine is a major determinant of an organism’s ability to survive in a terrestrial environment
Human kidney can produce a maximal urinary concentration of 1200-1400 most/kg, 4-5 times higher than plasma osmolality (300 most/kg)
Urinary concentration takes place as fluid moves through ____ ____.
Collecting duct
Medullary interstitial fluid around collecting ducts is hyperosmotic
Therefore, when ADH increases, water diffuses out of ducts
Countercurrent multiplier and exchange system
Sets up and maintains high medullary interstitial osmolality
Present in 30-40% of nephrons whose loops are long, extending into inner medulla. Glomeruli for these nephrons are in juxtamedullary area and mid cortex
What’s a countercurrent system?
fluid flowing in opposite directions in adjacent tubules
Anatomy of tubules and blood vessels in MEDULLA fit this definition
Countercurrent Multiplication
Most important element is active pumping of sodium ions from ascending limb of Henle’s loop into medullary interstitial
Movement of water in response to increasing interstitial osmolality is passive; at any given level of the loop, acts to equilibrate osmolalities between interstitial and descending limb
New fluid is constantly entering; as it moves down loop, its osmolality increases
Final result: although the gradient across the loop is never more than 200 mOsm/kg, a large gradient (900-1100 most/kg) exists from top to bottom
Thus, in the presence of ADH, water in the collecting duct readily diffuses into hyperosmotic intersitium
When water diffuses into interstitium, why doesn’t this dilute the interstitium, thus destroying the gradient?
B/c of Vasa Recta
Vasa Recta
System of passive exchange capillaries closely associated w/ Henle’s Loop
Solutes diffuse in, water comes out - as blood descends, it encounters high medullary interstitial solute concentrate
As blood leaves, its (Osm) only slightly higher than when it entered and only small amounts of solutes and carried away from medulla
- Descending limb: solutes (Na+) diffuse in, water diffuses out, blood becomes hyperosmotic
- Ascending limb: solutes diffuse out, water diffuses in, blood approaches isosmotic
