Glomerular Filtration, Reabsorption, Secretion, Loop of Henle and Regulation of Osmolarity Flashcards
1
Q
What are the main functions of the kidney?
A
Filtration
Reabsorption
Secretion
2
Q
What does filtration result in?
A
Formation of an essentially protein-free filtrate of plasma, about 20% of what is excreted, at the glomerular capillaries
3
Q
What is the normal glomerular filtration rate?
A
180 l/day
4
Q
What does the high GFR mean?
A
That the kidney has ample opportunity to precisely regulate ECF volume and composition and eliminate harmful substances
5
Q
What occurs in reabsorption?
A
Substances that the body wants are reabsorbed, those it doesn’t want stay in the tubule and are excreted in urine
6
Q
What occurs in secretion?
A
Substances can be specifically removed from the body in this way e.g. drugs, toxins
7
Q
What is the blood flow that the kidneys receive?
A
Around 1,200 ml/min
8
Q
What percentage of cardiac output do the kidneys receive?
A
20-25%
9
Q
What explains the vulnerability of the kidneys to damage by vascular disease?
A
The fact that they normally receive such high blood flow
10
Q
In what amount of time does a volume of blood equal to the total blood volume pass through the renal circulation?
A
< 5 mins
11
Q
What is filtered through to the Bowman’s capsule?
A
None of the red cells and only a fraction of the plasma is filtered through into the Bowman’s capsule
The remainder passes through the efferent arterioles into the peritubular capillaries and then to the renal vein
12
Q
What percentage of total blood volume foes plasma constitute?
A
55%
13
Q
What is the renal plasma flow?
A
660ml/min
55% of 1200 ml/min = 660 ml/min
14
Q
What is the normal filtration fraction?
A
19%
GFR normally 125ml/min so filtration fraction is 125/660 x 100 = 19%
i.e. 19% of the renal plasma becomes glomerular filtrate
15
Q
What is glomerular filtration dependent on?
A
The balance between the hydrostatic forces favouring filtration and the oncotic pressure forces favouring reabsorption (Starling’s forces)
16
Q
How are many substances reabsorbed?
A
By carrier mediated transport systems
17
Q
What substances are reabsorbed by carrier mediated transport systems?
A
Glucose Amino acids Organic acids Sulphate Phosphate ions
18
Q
What is the maximum transport capacity due to?
A
Saturation of the carriers
19
Q
What happens once maximum transport capacity is reached?
A
All carriers are saturated, so anything exceeding this capacity will remain in the tubule and will eventually be secreted
20
Q
What do carrier proteins enable?
A
Larger molecules to cross the membrane
21
Q
What is the capacity of carrier proteins limited by?
A
The number of carriers
22
Q
What is the renal threshold?
A
The plasma threshold at which saturation occurs
23
Q
What do secretory mechanisms transport?
A
Transport substances from the peritubular capillaries into the tubule lumen and therefore provide a second route into the tubule
24
Q
Why is tubular secretion important for substances that are protein-bound?
A
Because their filtration at the glomerulus is very restricted, for potentially harmful substances tubular secretion allows them to be eliminated more rapidly
25
What do Tm limited carrier-mediated secretory mechanisms act on?
A large number of endogenous and exogenous substances
26
Why can the organic acid mechanism which secretes lactic and uric acid also be used for penicillin, aspirin and para-amino-hippuric acid?
Because carrier mechanisms are not very specific
27
What can organic base mechanisms for choline and creatinine also be used for?
Morphine and atropine
28
Where are lactic acid, penicillin, choline and morphine etc. secreted?
At the proximal tubule
29
What is the permeability of the glomerular barrier?
Selectively permeabile
30
What is the filterability of solutes across the glomerular filtration barrier determined by?
Molecular size
Electrical charge
Shape
31
What prevents the filtration of blood cells but allows all components of blood plasma to pass through?
Fenestration of glomerular endothelial cells
32
What prevents the filtration of larger proteins?
The basal lamina of the glomerulus
33
What prevents the filtration of medium-sized proteins?
The slit membrane between the pedicels
34
Why is glomerular capillary pressure (Pgc) higher than in most of the other capillaries in the body?
Because the afferent arteriole is short and wide so offers little resistance to flow, so the blood arriving at the glomerulus still has a high hydrostatic pressure
35
What arteriole is long and narrow?
Efferent arteriole
36
What arteriole is short and wide?
Afferent arteriole
37
What does high post-capillary resistance, offered by the efferent arteriole, cause?
Hydrostatic pressure upstream to be increased while pressure downstream is decreased
38
What is hydrostatic pressure?
The pressure exerted by a fluid at equilibrium at a given point within the fluid, due to the force of gravity
39
What contributes to the very high glomerular capillary pressure?
Both the afferent and efferent arterioles
40
At the glomerular capillaries, what is the relationship between the hydrostatic pressure and oncotic pressure?
Hydrostatic pressure favouring filtration always exceeds oncotic pressure
41
What capillaries are responsible for reabsorption?
Peritubular capillaries
42
Why must an enormous amount of fluid be reabsorbed back into the peritubular capillaries?
Because 180l/day are filtered through the glomerulus into the renal tubule but only 1-2l/day are excreted as urine
43
Why is there a large pressure drop in the efferent arteriole?
Because it offers resistance along its entire length
44
What does the large pressure drop in the efferent arteriole mean?
Hydrostatic pressure is very low
45
Why is Ppc very low in capillaries?
Because hydrostatic pressure is overcoming frictional resistance in the efferent arterioles
46
What concentrates the plasma protein in the peritubular capillaries?
Loss of 20% of plasma
47
Since 20% of the plasma has filtered into the Bowman's capsule in the glomerulus, what happens to the blood remaining in the efferent arteriole and peritubular capillaries?
Blood remaining has a higher concentration of plasma proteins and therefore increased IIp
48
What is the net result of the low Ppc and high IIp?
The balance of Starling's forces in the peritubular capillaries is entirely in favour of reabsorption
49
What percentage of water, glucose, sodium and urea is filtered at the glomerulus and reabsorbed within the tubule?
99% water
100% glucose
99.5% sodium
50% urea
50
Where are water, glucose, sodium and urea mainly reabsorbed?
At the proximal tubule
51
What is the primary factor affecting glomerular filtration?
Glomerular capillary pressure
52
What is glomerular capillary pressure dependent on?
Afferent and efferent arteriolar diameter and therefore the balance of resistance between them
53
The diameters of the afferent and efferent arterioles is subject to extrinsic control via what?
Sympathetic vasoconstrictive nerves - causing afferent and efferent constriction, greater sensitivity of the afferent arteriole
Circulating catecholamines - constriction primarily of the afferent arterioles
Angiotensin II - constriction of the efferent arterioles at low concentration, and of both afferent and efferent arterioles at a higher concentration
54
What intrinsic ability does renal vasculature exhibit?
Well-developed intrinsic ability to adjust its resistance in response to changes in arterial blood pressure
55
What does the intrinsic ability of the renal vasculature to adjust its resistance in response to changes in arterial BP allow?
Keeps blood flow and GFR essentially constant, allowing autoregulation
56
Over what range of MBP is renal vascular autoregulation effective?
60-130mmHg
Below 60mmHg, filtration falls and then ceases altogether when it falls to 50mmHg
57
What happens to the afferent arterioles if mean arterial pressure increases?
There is an automatic increase in afferent arteriolar constriction, preventing a rise in glomerular Pgc, dilatation occurs if pressure falls
58
What is autoregulation independent of?
Nerves or hormones, so occurs in denervated and isolated perfused kidneys
59
What does the interaction between intrinsic and extrinsic controls allow?
In situations where blood volume/BP face serious compromise e.g. in haemorrhage, activation of the sympathetic vasoconstrictive nerves can override autoregulation, which allows more blood to be liberated for more immediately important organs
60
What volume of blood can be provided to perfuse other organs at the expense of the kidney?
As much as 880ml of blood per minute
61
What can prolonged reduction in renal blood flow result in?
Irreparable damage which may lead to death because of disruption of the kidneys role in homeostasis
62
What does endurance training provide?
Endurance training involves the adaptation of skeletal muscle so that its requirement for blood flow becomes more efficient and therefore there is less need to take blood flow from the kidneys
63
Glucose is freely filtered, what does this mean?
Whatever its plasma concentration is, it will be filtered
64
In humans, what plasma concentration of glucose is reabsorbed?
Up to 10mmol/l will be reabsorbed
Any plasma glucose concentration higher than this will not be reabsorbed and so will be excreted and present in the urine meaning the renal plasma threshold for glucose has been exceeded
65
What regulates glucose concentration?
Insulin and the counter-regulatory hormones, the kidneys do not regulate glucose concentration
66
In a normal glucose concentration, Tm is set way above any possible level of non-diabetic glucose plasma concentration, what does this ensure?
Ensures that all of the valuable nutrient is reabsorbed
67
What is the appearance of glucose in the urine of diabetic patients due to?
Failure of insulin - not the failure of the kidney
68
Why does urinary excretion of amino acids not occur?
Tm is set so high that it doesn't occur
69
How can the kidney regulate some substances by means of the Tm mechanisms?
Because the Tm is set at a level whereby the normal plasma concentration causes saturation, any rise above the normal level will be excreted, achieving its plasma regulation e.g. sulphate and phosphate ions
70
What are the most abundant ions in the ECF?
Sodium ions
71
What percentage of sodium reabsorption occurs in the proximal tubule?
65-75%
72
What percentage of sodium is reabsorbed?
99.5%
73
How does reabsorption of sodium occur?
By active transport, which establishes a gradient for Na+ across the tubule wall
74
What drives the reabsorption of sodium?
The Na+ pump
75
Where are sodium pumps located?
On the basolateral surfaces where there is a high density of mitochondria
76
What does the sodium pump work to do?
Works to decrease Na+ concentration int he epithelial cells, increasing the gradient for Na+ ions to move into cells passively across the luminal membrane
77
Where is there a higher permeability to Na+ ions than most other membranes in the body? Why is this?
The brush border of the proximal tubule cells - partly because of the enormous surface area offered by the microvilli and also due to the large number of Na+ ion channels which facilitate the passive diffusion of Na+
78
How do negative ions diffuse across the proximal tubular membrane?
Diffuse passively across the proximal tubular membrane down the electrical gradient established and maintained by the active transport of Na+
79
What creates the osmotic force which draws H2O out of the tubules?
The active transport of Na+ out of the tubule, followed by Cl-, creates an osmotic force
80
What concentrates substances left in the tubule? What does this create?
H2O removed from the tubule fluid concentrates the substances left in the tubule, creating outgoing concentration gradients
81
What does the rate of reabsorption of non-actively reabsorbed solutes depend on?
The amount of H2O removed, which will determine the extent of the concentration gradient
The permeability of the membrane to any particular solute
82
Why does only 50% of urea reabsorbed?
The tubule membrane is only moderately permeable to urea, so only 50% is reabsorbed and the remainder stays in the tubule
83
What substances is the tubular membrane impermeable to?
Insulin
| Mannitol
84
What does the impermeability of the tubular membrane to some substances mean?
Despite a concentration gradient being established which favours their reabsorption, they cannot gain access through the tubule membrane, so all that is filtered stays in the tubule and passes out in the urine
85
What establishes the gradient down which other ions and solutes pass passively?
The active transport of Na+
86
What effect will anything that decreases active transport have?
Anything which decreases active transport will disrupt renal function
87
Why is active transport of Na+ also important for the carrier mediated transport systems?
As some molecules e.g. glucose and amino acids share the same carrier molecules of Na+
88
What does high Na+ concentration in the tubule facilitate?
Glucose transport, while low concentration will inhibit it
89
What is Na+ reabsorption linked to?
HCO3- ion reabsorption
90
What is the major cation in the cells of the body?
K+
| The maintenance of K+ balance is essential for life
91
What is the normal ECF [K+]?
4mmoles/l
92
What happens if [K+] increase to 5.5 mmoles/l?
Hyperkalaemia
- reduced resting membrane potential of excitable cells
- ventricular fibrillation and death
93
What happens if [K+] falls to < 3.5 mmoles/l?
Hypokalaemia
- increased resting membrane potential
- hyperpolarises muscle and cardiac cells
- cardiac arrhythmias and death
94
What is the renal handling of K+?
Complex
- filtered at the glomerulus
- reabsorbed primarily at the proximal tubule
95
What are changes in K+ excretion due to?
Changes in its secretion in the distal parts of the tubule
96
What effect will any increase in renal tubule cell [K+] due to increased ingestion have?
Will increase secretion, while a decrease in intracellular K+ will do the opposite
97
What is K+ secretion regulated by?
Aldosterone
98
What stimulates aldosterone release?
An increase in [K+] in the ECF bathing the aldosterone secreting cells
99
What does aldosterone stimulate?
Increase in renal tubule cell K+ secretion
| Na+ reabsorption at the distal tubules, by a different reflex pathways
100
Where are H+ ions actively secreted from?
From the tubule cells into the lumen
101
What are the functions of the proximal tubule?
Major site of reabsorption
65-75% of all NaCl and H2O
Reabsorption of nutritionally important substances
102
How much protein per day gets through the proximal tubule?
30g protein/day, around 0.5% of the total amount which is presented at the glomerulus
particularly albumin
103
What happens to protein which gets through the proximal tubule?
It is completely reabsorbed by a Tm carrier mechanism in the proximal tubule
104
What are the features of many drugs and pollutants?
Many are non-polar and therefore highly lipid-soluble
105
What effect does the lipid solubility of many drugs and pollutants have?
Makes it difficult to excrete them
106
How is the excretion of lipid-soluble drugs and pollutants facilitated?
Liver polarises them to polar compounds, reducing their permeability and facilitating their excretion
107
Why is the fluid that leaves the proximal tubule isosmotic with plasma?
Because all of the solute movements are accompanied by equivalent H2O movements, so the osmotic equilibrium is maintained
108
Where do all of the nephrons have their proximal and distal tubules?
In the cortex
109
What is the system essential for water balance attributable to?
The loops of Henle of the juxtamedullary nephrons
110
What can the kidneys do through the system for water balance in the loops of Henle?
The kidney is able to produce concentrated urine in times of H2O deficit, a major determinant of our ability to survive without water
111
What is the maximum concentration of urine that can be produced by the human kidney?
1200-1400 mOsmoles/l
| 4x more concentrated than plasma
112
What concentration do the urea, sulphate, phosphate and other waste products and non-waste ions which must be excreted each day amount to?
What does this require?
Around 600 mOsmoles/l
This requires a minimum obligatory H2O loss of 500ml
As long as the kidneys are functioning, this volume will be excreted
113
What is the minimum urine concentration in humans?
30-50 mOsmoles/l
114
Why are the kidneys able to produce urine of varying concentration?
Because the loops of Henle of the juxtamedullary nephrons act as a counter-current multipliers
115
What happens in the counter-current system?
Fluid flows down the descending limb and up the ascending limb
116
What are the critical characteristics of the loops of Henle which make them counter current multipliers?
The ascending limb of the loop of Henle actively co-transports Na+ and Cl- ions out of the tubule lumen into the interstitial
The ascending limb is impermeable to H2O
The descending limb is freely permeable to H2O but relatively impermeable to NaCl
117
What happens in the loop of Henle if it is filled with a stationary isosmotic fluid?
Active removal of NaCl from the ascending limb
| Osmolarity in the tubule decreases and osmolarity in interstitium increases
118
What happens if the descending limb is exposed to a greater osmolarity in the interstitium?
H2O will move out to equate the osmolarity
119
Fluid enters at the proximal tubule and leaves at the distal tubule, what does this mean?
Concentrated fluid in the descending limb rounds the bend and delivers a high concentration to the ascending limb, resulting in active NaCl removal, further concentrating the interstitium
120
What does the greater concentration of the descending limb mean?
That there is a greater concentration of the interstitium due to the addition of salt from the ascending limb
121
Where is the fluid in the tubule concentrated and diluted?
Progressively concentrated as it moves down the descending limb
Progressively diluted as it moves up the ascending limb
122
At any horizontal level, what is the gradient between the ascending limb and the interstitium?
200mOsmole
123
What does counter current flow multiply?
The gradient
124
What happens if the active transport of NaCl out of the ascending limb is abolished?
All of the concentration differences are lost and the kidney can only produce isotonic urine
125
What does the counter-current multiplier achieve?
Concentrates fluid on the way down and promptly re-dilutes it on the way back up - not by adding water but by removing NaCl
One consequence of this is that 15-20% of the initial filtrate is removed from the loop of Henle (up to 36l)
Fluid which enters the distal tubule is more dilute than plasma
126
What is the significance of the counter-current multiplier?
It creates an increasingly concentrated gradient in the interstitium
Also delivers hypotonic fluid to the distal tubule
127
What is the Vasa Recta?
The specialised arrangement of the peritubular capillaries of the juxtamedullary nephrons, which also participate in the counter-current mechanism by acting as counter-current exchangers
128
What would happen if medullary capillaries drained straight through?
They would carry with them the NaCl removed from the loop of Henle and abolish the interstitial gradient
This does not happen as they are arranged as hairpin loops and therefore do not interfere with the gradient
129
What are the functions of the vasa recta?
Provide oxygen for the medullar
In providing O2, they must not disturb the gradient
Remove volume from the interstitium, up to 36l/day
130
Why is the balance of Starling's forces in favour of reabsorption?
Because of the high IIp and high Pt due to tight renal capsule which drives fluid into the capillaries
131
What does the slow flow rate through the vasa recta allow?
Plenty of time for equilibration to occur within the interstitium, further ensuring that the medullary gradient is not disturbed
132
What causes central diabetes insipidus?
Hypothalamus area synthesising ADH may become diseased due to tumours or meningitis, or may be damaged during surgery
133
What happens if the collecting duct is insensitive to ADH?
Peripheral diabetes insipidus
134
What is the characteristic feature of diabetes insipidus?
Passage of very large volumes of very dilute urea
135
What is polyuria?
> 10 l/day urine
136
What is polydipsia?
Drinking large volumes of urine
137
Why can ADH not be given for treatment of peripheral diabetes insipidus?
Thirst mechanism is important for survival
138
What is peripheral diabetes insipidus usually secondary to?
Hypercalcaemia or hypokalaemia
