Glomerular Filtration, Reabsorption, Secretion and Loop of Henle Flashcards
How much blood flow does the kidneys receive? And how much of the CO?
1200mls/min
20-25% total CO
Normal GFR value
125mls/min
Factors affecting glomerular filtration
Balance between hydrostatic forces favouring filtration and
Oncotic pressure forces favouring reabsorption (starlings forces)
What determines the filterability of solutes across the glomerular filtration barrier?
Molecular size
Electrical charge
Shape
Layers of the glomerular barrier
- Fenerstrations/pores of glomerular endothelial cell; prevents filtration of blood cells but allows all components of blood plasma to pass through
- Basal lamina of glomerulus; prevents filtration of larger proteins
- Sit membrane between pedicles; prevents filtration of medium sized proteins
Why is the glomerular capillary pressure higher than in most capillaries of the body?
Because the afferent arteriole is short and wide and therefore offers little resistance to flow
How does the efferent arteriole of the glomerular capillaries have a high post capillary resistance?
Unique arrangement - Long and narrow
What is the golden rule of the circulation?
If you have high resistance, hydrostatic pressure upstream is increased, while the pressure downstream is decreased
Which from the afferent and efferent arterioles contribute to the very high glomerular capillary pressure?
Both
At the glomerular capillaries, hydrostatic pressure vs oncotic pressure
Hydrostatic - favouring filtration always exceeds the oncotic pressure
What is the only thing that occurs at the glomerular capillaries?
Filtration
What is responsible for reabsorption?
Peritubular capillaries
How much is filtered through the glomerulus into the renal tubule? How much of this is excreted as urine?
180 L/day
1 - 2L is excreted as urine
Why is only 1 - 2L of 180L / day excreted as urine?
An enormous amount of fluid must be reabsorbed back into the peritubular capillaries
What arteriole has important effects on starlings forces in the peritubular capillaries?
Efferent arteriole
Hydrostatic pressure in efferent arteriole
Very low
IIp and concentration of plasma proteins in the efferent afteriole and peritubular capillaries
Increased
The balance of pressures in the peritubular capillaries are entirely favour of what?
Reabsorption
How much of H20 filtered at the glomerulus is reabsorbed within the tubule?
99%
How much of glucose filtered at glomerulus is reabsorbed within the tubule?
100%
How much of Na+ filtered at the glomerulus is reabsorbed within the tubule?
99.5%
How much of urea filtered at the glomerulus is reabsorbed within the tubule?
50%
Where in the tubule are substances mostly reabsorbed?
Proximal convoluted tubule
Which occurs at the glomerular capillaries?
Filtration
Mechanisms of reabsorption
- Carrier mediated transport systems
- Reabsorption of Na+ ions
- Tubular secretion
What substances are reabsorbed by carrier mediated transport systems?
Glucose Amino acids Organic acids Sulphate ions Phosphate ions
How do carrier mediated transport systems work to reabsorb substances?
Carriers have a maximum transport capacity Tm which is due to saturation of carriers
If Tm is exceeded, then the excess substrate enters the urine
What is the renal threshold?
The plasma threshold at which saturation occurs
Filtrationn of glucose
Freely filtered
What is the renal plasma glucose threshold?
10mmoles/l
What is responsible for glucose regulation?
Insulin
Counter regulatory hormones
Normal plasma glucose concentration
5 mmoles/l
What is the name for the presence of glucose in the urine?
Glycosuria
What is the most abundant ion in the ECF?
Na+
What % of Na+ ion reabsorption occurs in the proximal tubule?
65 - 75%
How are Na+ ions reabsorbed?
Active transport
- Na+ pumps
Active transport of Na+ ions
Active Na+ pumps are located on the basolateral surfaces where there is a high density of mitochondria
This decreases Na+ in the epithelial cells, increasing the gradient (a secondary gradient) for Na+ ions to move into the cells passively across the luminel membrane.
So links the passive transport on the tubule lumen to the active transport on the intralumineal membrane
Are Na+ ions permeable at cell membranes?
No
Why does the brush border of the proximal tubule cells have a higher permeability to Na+ ions than most other membranes in the body?
Enourmous surface area offered by the microvilli and the large number of Na+ ions channels, which facilitate this passive diffusion of Na+
What is the reabsorption of Na+ ions key to?
The reabsorption of the other components of the fitrate
How do negative ions diffuse across the proximal tubule membrane?
Passively across the proximal tubular membrane down the electrical gradient established and maintained by the active transport of Na+
What does the active transport of Na+ out of the tubule followed by Cl- create?
An osmotic force, drawing H20 out of the tubules
What does H20 removed by osmosis from the tubule fluid result in?
It concentrates all the substances left in the tubule (e.g. glucose, urea) creating outgoing concentration gradients
What does the rate of reabsorption of these non actively reabsorbed solutes depend on?
Amount of H20 removed (which will determine the extent of the concentration gradient for other substances). More concentrated = easier to transport substances
The permeability of the membrane to any particular solute
Permeability of the tubule membrane to urea
Moderately permeable to urea so that only about 50% is reabsorbed, the remainder stays in the tubule
Permeability of the tublar membrane to insulin and mannitol
Impermeable
What establishes the gradients down which other ions, H20 and solutes pass passively?
Active transport of Na+
Anything which decreases active transport of Na e.g. decreased blood flow results in what?
Disruption of renal function
Importance of Na+ transport
- Active transport of Na+ establishes the gradient down which other ions, H20 and solutes pass passively
- Carrier mediated transport systems - substances such as glucose, amino acids etc share the same carrier molecule as Na+ (symport)
- Na+ reabsorption is linked to HCO3- ion reabsorption
Effects of [Na] concentration in the tubule on glucose transport
High [Na+] = facilitates glucose transport
Low [Na+] = inhibits glucose transport
What drives the co transport of sodium and glucose?
ATP hydrolysis
How does tubular secretion work?
Secretory mechanisms transport substances FROM the peritubular capillaries INTO the tubule lumen and therefore provides a second route into the tubule
What molecules are tubular secretion important for?
Those that are protein bound
e.g. drugs
Where are all of the substances in tubular secretion secreted?
In the proximal tubule
What are the 3 basic renal processes?
Filtration
Reabsorption
Secretion
Factor affecting GFR
Pressure in the glomerular capillaries
What is the pressure in the glomerular capillaries dependent on?
The afferent and efferent arteriolar diameter and therefore the balance of resistance between them
Extrinsic control of pressure in the glomerular capillaries
Sympathetic VC nerves
- afferent and efferent constriction
- Greater sensitivity of afferent arteriole
Circulating catecholamines
- constrict primary afferent
Angiotensin II
- constriction of efferent at [low], both afferent and efferent at [high]
What is autoregulation independent of?
Nerves
Hormones
Autoregulatory range in men
60 - 130 mmHg
In what situations would autoregulation be overriden and why?
Blood volume / BP face serious compromise e.g. in haemorrhage.
Liberates blood for more immediately important organs
What is the renal threshold?
The plasma threshold at which saturation occurs
What is the major cation in the cells of the body?
K+
Normal ECF [K+]
approx. 4 mmoles/l
Hyperkalaemia value
5.5 mmoles/l
Hypokalaemia value
< 3.5 mmoles/l
What does hyperkalaemia result in?
Decrease resting membrane potential of excitable cells and eventually ventricular fibrillation and death
What does hypokalaemia result in?
Increases resting membrane potential i.e. hyperpolarises muscle, cardiac cells -> cardiac arrythmias and eventually death
Where is K+ reabsorbed?
Primarily at the proximal tubule
What are changes in K+ excretion due to?
Its secretion in distal parts of the tubule
K+ secretion is regulated by what?
Adrenal cortical hormone aldosterone
An increase in [K+] in ECF bathing the aldosterone secreting cells does what?
Stimulates aldosterone release which circulates to the kidneys to stimulate increase in the renal tubule cell K+ secretion
What does aldosterone also do?
Stimulates Na+ reabsorption at the distal tubule but by a different reflex pathway
Where is the major site of reabsorption?
Proximal tubule
Parts of the Loop of Henle
Ascending Limb
Descending Limb
What is the maximum concentration of urine that can be produced by the human kidney?
1200 - 1400 mOsmoles/l
What is the minimum obligatory H20 loss needed (even if we do not drink) and why is this?
500mls
Due to urea, sulphate, phosphate, other waste products and non waste ions (Na+ and K+) which must be excreted each day to approx. 600mOsmoles
Minimum urine concentration a man can produce
30 - 50 mOsmoles/l
What nephrons are the loops of Henle in?
Juxtamedullary nephrons
How are kidneys able to produce urine of varying concentration?
Because of the loops of Henle acting as counter-current multipliers
How does the counter current of Loop of Henle work?
Fluid flows down the descending limb and UP the ascending limb, in osmotic correlation to each other
Fluid enters at the proximal and leaves at the distal tubule - concentrated fluid in the descending limb rounds the bend and delivers a high conc to the ascending limb
- active NaCl removal
- further concentrates the interstitium
So concentrates fluid on the way down and promptly re-dilutes it on the way back up, NOT by adding H20 but by removing NaCl
What is a counter current?
Something that flows passed itself
What are the critical characteristics of the loops which makes them counter current multipliers?
- The ascending loop actively co transports Na+ and Cl- ions out of the tubule lumen and into the interstitium
- The descending limb is freely permeable to H20 but relatively impermeable to NaCl
What is the ascending limb impermeable to?
H20
What is the overwhelming significance of the counter current multiplier?
It creates an increasingly concentrated gradient in the interstitium
Also deliverys hypotonic fluid to the distal tubule
What are the vasa recta?
The specialised arrangement of the peritubular capillaries of the juxtamedullary nephrons acting as counter current exchangers
Permeability of vasa recta
Permeable to H20 and solutes and therefore equilibrium with the medullary interstitial gradient
Functions of the vasa recta
Providing O2 for medulla
In providing O2 must not disturb gradient
Removes volume from the interstitium, up to the 36l/day
Where is the site of water regulation?
The collecting duct
What is the collecting duct permeability under control of?
ADH
What does ADH stand for?
Anti diuretic hormone
Another name for ADH
Vasopressin