Lecture 5: Water transport in the kidney I Flashcards
how is homeostasis maintained in the kidney
water intake and output must be equal
what are the bodies three main sources of water
1) ingested wate
2) water contained in the foods eaten
3) water produced by aerobic metabolism as mitochondria convert foodstuffs and O 2 to CO 2 and H 2 O
how is homeostasis disrupted in normal day to day activities and how does the body respond to this change?
we consume about 20-25% more salt and water and other ions per day than needed to replace obligatory losses through sweat, breathing and faeces
what products does the kidney want to eliminate
urea generated by metabolism
how much renal plasma flow does the kidney filter out
20%
reabsorbs back the salt and water and other molecules that it wants to keep
define glomerular filtration rate
ate is the rate at which fluid which is virtually free of protein is filtered from the glomerular capillaries into Bowman’s capsule
what is the normal avergae GFR
125ml/min
why is the concentration of substances in the glomerular filtrate in the bowmans capsule almost the same as that in plasma?
because the substances in the plasa are freely filtered
how is filtrate modified in the nephron
- the reabsorption of water and certain solutes back into the blood
- secretion of substances from the peritubular capillaries into the tubules thereby forming urine.
excretion = ?
excretion = filtration - reabsorption + secretion
how much solute does the kidney excrete a day and how much urnine output is that?
- ~600 milliosmoles/day
- For average conditions of water and solute intake and output, these 600 milliosmoles are dissolved in a daily urine output of 1500 mL.
- A key principle is that, regardless of the volume of water they excrete, the kidneys must excrete ~600 milliosmoles/day. Stated somewhat differently, the product of urine osmolality and urine output is approximately constant
to excrete a wide range of water volumes, the human kidney must produce urine having a wide range of osmolalities. what is the range of urine osmolality the kidney can produce?
as urine output is apporximately constant.
- water intake high - generate urine having an osmolality as low as ~40 mOsm.
- water intake low - necessary to conserve water (e.g., with restricted water intake or excessive loss by sweat or stool), generating urine with an osmolality as high as ~1200 mOsm.
How is GFR regulated?
GFR=Filtration Constant X (Hydrostatic Glomerulus Pressure-Hydrostatic Bowman’s Capsule Pressure)-(Osmotic Glomerulus Pressure+Osmotic Bowman’s Capsule Pressure).
What two mechanisms does the kidney use to regulate GFR?
- intrinsic: tubuloglomerular feedback, renin, autoregulation (myogenic response)
- extrinsic: sympathetic nervous system, ANP
Explain how tubuloglomerular feedback works?
- juxtaglomerular apparatus (JGA) and a paracrine signaling mechanism utilizing ATP, adenosine, and nitric oxide (NO).
- stimulates contraction or relaxation of afferent arteriolar smooth muscle cells.
- DCT (Distal Convoluted Tubule) is in close contact with the afferent and efferent arterioles of the glomerulus.
- macula densa cells of the tubule respond to changes in the fluid flow rate and Na+ concentration.
- When blood pressure increases for a short duration, more blood flows through the glomerulus and therefore more filtrate is produced. (takes path of least resistance)
- This results in a decrease in proximal tubule reabsorption
- This increases the concentration of NaCl in the distal tubule which is detected by the Macula Densa
- The Macula Densa releases adenosine resulting in the vasoconstriction of the afferent arteriole
- If blood pressure decreases the opposite occurs
- Vasoconstriction of the afferent arteriole causes a decrease in pressure in the glomerulus and a decrease in GFR, therefore keeping it constant
explain how the myogenic response works
the reflex response of the afferent arterioles to changes in blood pressure.
- Increased blood pressure increases the tension in the vascular wall, and the vascular smooth muscle contracts.
- Decreased blood pressure decreases the tension and the smooth muscle relaxes.
what kind of feedback mechanism is tubuloglomerular feedback?
negative feedback system - tries to reverse the effect of the stimulus
What extrinsic method does the kidney use to regulate GFR?
sympathetic nervous system
explain how the sympathetic nervous system regulates GFR
The kidneys are controlled autonomically by the sympathetic nervous system via the celiac plexus and the splenic nerves.
- Reduction of sympathetic stimulation = vasodilation and, increased blood flow
- Increase in sympathetic stimulation = vasoconstriction and decreased flow.
Explain what happens when sympathetic activity to the kidney increases.
- vasoconstriction and decreased blood flow leads to decreased filtration
- increases in renin secretion rate
- decreases in urinary sodium excretion by increasing renal tubular sodium reabsorption
what triggers an increase in sympathetic nervous activity to the kidney
- decrease in blood pressure
what happens when blood pressure falls in the kidney
- increased sympathetic activity
- RAAS triggered
- increased vasopressin (increases water reabsorption in collecting ducts ADH)
what is tubular reabsorption
occurs when the kidneys reabsorb useful substances, such as glucose, amino acids, and electrolytes, from the filtrate back into the bloodstream
how does the kidney reabsorb molecules back into the bloodstream and where does this occur?
- across the tubular epithelial membrane into the renal interstitial fluid and then through the peritubular capillary membrane back into the blood. They can be transported through the cell membrane itself or through the spaces between the cell junctions.
- basolateral Na-K ATPase
Explain how the Na-K ATPase works
- system hydrolyses ATP and uses the released energy to…
- transport sodium ions out of the cells into the interstitium.
- potassium ions are transported from the interstitium to the inside of the cell
- low intracellular sodium and a high intracellular potassium concentration maintained.
- creates a negative charge of around - 70 mV within the cell.
Why is the sodium gradient important in the kidney?
This sodium gradient is necessary for the kidney to filter waste products in the blood, reabsorb amino acids, reabsorb glucose, regulate electrolyte levels in the blood, and to maintain pH
Where does the majority of reabsorption occur, what is reabsorbed
- proximal convoluted tubule
- water and solutes within the PCT are transported into the bloodstream.
- via bulk transport.
- The solutes and water move from the PCT to the interstitium and then into peritubular capillaries.
- 95% glucose, amino acids, peptides, sodium
- reabsorbs two thirds of the filtered fluid isosmotically (i.e., the fluid reabsorbed has nearly the same osmolality as plasma)
how does the PCT reabsorb glucose
- active transport
- sodium glucose co-transporter
- sodium gradient maintained by sodium potassium ATPase
what does the TF/P ratio show
concentration of substance X in tubular fluid (TF) and plasma (P) at any given point in the nephron
Explain the saturation kinetics of cotransporters in the PCT
- For substances that are actively reabsorbed (eg. glucose) or secreted, there is a limit to the rate of transportation, often referred to as the transport maximum.
- This is primarily due to saturation of the transport systems involved
- as more glucose is reabsorbed ratio has larger denominator (high plasma concentration, low tubular fluid concentration - see a decrease in osmolality)
Osmolality indicates the concentration of all the particles dissolved in body fluid
at the end of the PCT how much tubular fluid has been reabsorbed?
80%
what are the solute concentration trends at the end of the proximal convoluted tubule?
- There has been no change in sodium concentration because water passively follows the sodium.
- All of the glucose and amino acids have been reabsorbed
- The tubular fluid is also iso-osmotic with the initial filtrate. The missing osmoles (sodium) is replaced by urea.
