Renal physiology Flashcards
1
Q
How much of our body weight is water?
A
60%
2
Q
What is intracellular fluid?
A
Fluid inside the cells
3
Q
What is included in extracellular fluid? (3)
A
- Transcellular
- Plasma
- Interstitial
4
Q
What is transcellular fluid?
A
- Cerebrospinal fluid
- Urine stored in the bladder
5
Q
What is interstitial fluid?
A
Fluid surrounding cells which isn’t part of the plasma
6
Q
What is the K+ concentration in the intracellular fluid?
A
148 mM
7
Q
What is the K+ concentration in the extracellular fluid?
A
5 mM
8
Q
What is the Na+ concentration in the intracellular fluid?
A
10 mM
9
Q
What is the Na+ concentration in the extracellular fluid?
A
140 mM
10
Q
What is the Cl- concentration in the intracellular fluid?
A
4 mM
11
Q
What is the Cl- concentration in the extracellular fluid?
A
103 mM
12
Q
What is the protein concentration in the intracellular fluid?
A
55 mM
13
Q
What is the protein concentration in the interstitial fluid?
A
15 mM (More protein in the plasma which can't cross the endothelium)
14
Q
What determines the total volume of the extracellular fluid?
A
Na+ concentration
15
Q
How big is a kidney?
A
10 cm x 5.5 cm
16
Q
Where is the kidney located?
A
Between the 12th thoracic and 3rd lumbar vertebrae
17
Q
How much does a kidney weigh?
A
150g
18
Q
What is renal agenesis?
A
Absence of one or both kidneys
19
Q
How common is renal agenesis?
A
1 in 2500 foetuses
20
Q
How serious is renal agenesis?
A
Fatal
21
Q
What is ectopic kidneys?
A
When the kidneys develop in the wrong place
22
Q
How common is ectopic kidneys?
A
1 in 800 live births
23
Q
What are side effects of ectopic kidneys?
A
Increased risk of damage and stone formation
24
Q
What is a horseshoe kidney?
A
When the kidneys are fused across midline
25
How common is horseshoe kidney?
1 in 1000
26
What are side effects of horseshoe kidney?
Increased risk of stones and long term damage from stones
27
What is the capsule?
Fibrous layer surrounding the kidney for protection and structural integrity
28
What is the functional unit of the kidney?
Nephron
29
How many nephrons do you have per kidney?
1 - 1.5 million
30
What are the elements of the nephron? (6)
- Bowman's capsule
- Glomerulus
- Proximal tubule
- Loop of Henle
- Distal tubule
- Collecting duct
31
What are the 2 types of nephrons?
- Superficial
| - Juxtamedullary
32
What are superficial nephrons?
Glomerulus located near the outer part of the cortex and loop of Henle doesn't enter the inner medulla
33
What proportion of nephrons are superficial?
85%
34
What are juxtamedullary nephrons?
Glomerulus located at the edge of the cortex and loop of Henle reaches the inner medulla
35
What proportion of nephrons are juxtamedullary?
15%
36
Which type of nephron plays the biggest role in urine concentration?
Juxtamedullary
37
What is renal failure defined as?
Fall in glomerular filtration rate? (GFR)
38
What does renal failure cause? (2)
- Increase in serum urea
| - Increase in serum creatinine
39
What is acute renal failure?
Reversible
40
What is chronic renal failure?
- Irreversible
| - Progressive
41
What is the treatment for chronic renal failure? (2)
- Dialysis
| - Transplant
42
How do haemoglobin levels change with acute renal failure?
No change
43
How do haemoglobin levels change with chronic renal failure?
Decreases
44
How does the size of the kidney change with acute renal failure?
No change
45
How does the size of the kidney change with chronic renal failure?
Gets smaller
46
What is peripheral neuropathy?
Peripheral nerve damage causing sensory and motor issues
47
Which type of renal failure can cause peripheral neuropathy?
Chronic
48
Which type of renal failure can cause decreased haemoglobin levels?
Chronic
49
What is uraemia? (6)
- Thickening of glomerular membranes
- Damaged glomeruli
- Glomerulosclerosis
- Tubular atrophy
- Interstitial inflammation
- Fibrosis
50
What is glomerulosclerosis?
Progressive scarring of the glomeruli
51
What is tubular atrophy?
Loss of nephrons
52
What symptoms arise due to failure to excrete salt and water in renal failure? (3)
- Hypertension
- Hyperkalaemia
- Mild acidosis
53
What symptoms arise due to failure to excrete urea/creatinine and leak of protein into urine in renal failure? (5)
- Anorexia
- Nausea
- Vomiting
- Neuropathy
- Pericarditis
54
What is pericarditis?
Inflammation of the pericardium
55
What is erythropoietin?
Hormone produced by the kidneys
56
What symptoms arise due to failure to produce erythropoietin in renal failure? (2)
- Anaemia
| - Lethargy
57
What symptoms arise due to failure to excrete phosphate in renal failure? (3)
- Low serum calcium
- Metastatic calcification causes pruritus
- Bone disease (osteomalacia, osteoporosis)
58
What is metastatic calcification?
Deposition of calcium salts in normal tissue
59
What is pruritus?
Skin itching
60
What is osteomalacia?
Soft bones
61
What is osteoporosis?
Brittle bones
62
What is normal GFR?
125 ml/min
63
What are examples of congenital renal abnormalities? (3)
- Renal agenesis
- Ectopic kidneys
- Horseshoe kidney
64
What can cause chronic renal failure? (4)
- Glomerulonephritis
- Diabetes mellitus
- Hypertension
- Polycystic kidney disease
65
How is high phosphate levels treated?
Phosphate binders
66
How is acidosis treated?
Sodium bicarbonate
67
How is sodium retention treated?
Diuretics
68
What is the GFR in end-stage chronic renal failure?
5-10 ml/min
69
What is the GFR in severe chronic renal failure?
10-25 ml/min
70
What is the GFR in moderate chronic renal failure?
25-50 ml/min
71
What is the GFR in mild chronic renal failure?
50-75 ml/min
72
Where does filtration occur?
Glomerulus
73
Which arteriole does blood enter the glomerulus via?
Afferent arteriole
74
Which arteriole does blood leave the glomerulus via?
Efferent arteriole
75
How much of the plasma that enters the glomerulus is filtered out?
20%
76
How much ultrafiltrate is produced per day by both kidneys?
180 litres per day
77
What is the total plasma volume?
3 litres
78
What is the diameter of the glomerulus?
200 micrometres
79
Which molecules are too big to enter the ultrafiltrate?
- Blood cells
| - Plasma proteins
80
Which plasma protein is filtered?
Albumin (small, reabsorbed later)
81
What is paracellular transport?
Between cells through tight junctions
82
What is transcellular transport?
Across cells
83
How much of the filtrate is reabsorbed in the proximal tubule?
70%
84
How much of the water and Na+ in the filtrate is reabsorbed in the proximal tubule?
70%
85
How much of the glucose and amino acids in the filtrate is reabsorbed in the proximal tubule?
100%
86
How much of the bicarbonate (HCO3-) in the filtrate is reabsorbed in the proximal tubule?
90%
87
What is reabsorbed at the proximal tubule? (5)
- Water
- Na+
- HCO3-
- Glucose
- Amino acids
- PO4 2-
88
Which proteins are present on the basolateral membrane of proximal tubule epithelial cells? (3)
- Na+/K+ ATPase
- K+ channel
- Phosphate/bicarbonate/amino acid/glucose transporters
89
What is the purpose of the Na+/K+ pump on the basolateral membrane of proximal tubule epithelial cells?
Removes Na+ from the cell into the capillaries in order to set up the driving force for Na+ uptake at the apical membrane from the filtrate
90
What is the purpose of the K+ channels on the basolateral membrane of proximal tubule epithelial cells?
Sets a negative membrane potential to encourage Na+ to enter the cell from the filtrate
91
How is glucose absorbed into the blood at the proximal tubule?
- Co-transport with Na+ due to the Na+ concentration gradient via SGLT1/SGLT2 on the apical membrane
- Once inside the cell glucose diffuses into the blood across the basolateral membrane down its concentration gradient
92
Which proteins in the apical membrane of proximal tubule epithelial cells transport Na+ and glucose? (2)
- SGLT1
| - SGLT2
93
Where are SGLT1 and SGLT2 located in the nephron?
Apical membrane of proximal tubule epithelial cells
94
How are amino acids absorbed into the blood at the proximal tubule?
- Co-transport with Na+ via a transporter on the apical membrane
- Amino acids transported into the blood over the basolateral membrane
95
How is Na+ reabsorbed at the proximal tubule?
- Co-transport with glucose/amino acids/phosphate/exchanged with H+ into the cell
- Enters the blood via Na+/K+ ATPase on basolateral membrane
96
Which protein in the apical membrane of proximal tubule epithelial cells transport Na+ and phosphate?
NaPi2
97
Where is NaPi2 located in the nephron?
Apical membrane of proximal tubule epithelial cells
98
How is phosphate absorbed into the blood at the proximal tubule?
- Co-transport with Na+ via NaPi2
| - Diffuses across the basolateral membrane into the blood
99
How is water reabsorbed at the proximal tubule?
Follows Na+ reabsorption via paracellular transport
100
What is the effect of knocking out NaPi2 in mice?
Low plasma phosphate levels due to more phosphate lost in the tubular fluid
101
What issues are caused when the NaPi2 transporter isn't working properly?
- Increased calcification (calcium phosphate)
- Intraluminal stones (nephrolithiasis)
- Nephrocalcinosis
- Leads to damage and possible renal failure
102
What does the von Kossa stain highlight?
Calcium phosphate
103
Which protein in the apical membrane of proximal tubule epithelial cells exchanges Na+ and H+?
NHE3
104
How does NHE3 work?
Transports Na+ into the cell and H+ out into the tubular fluid
105
Where is NHE3 located in the nephron?
Apical membrane of proximal tubule epithelial cells
106
How is HCO3- reabsorbed in the proximal tubule?
- H+ enters tubular fluid via NHE3 and combines with HCO3- to form H2CO3
- H2CO3 splits into CO2 and water via carbonic anhydrase which enter the cell (water via aquaporins)
- CO2 and water reform H2CO3 which then dissociates into H+ and HCO3-
- HCO3- reabsorbed via Na+ cotransporter, H+ recycled
107
Which protein transports HCO3- from the proximal tubule cell into the blood?
- Na+/HCO3- co-transporter
| - 3Na+ and 1 HCO3- transported at a time
108
What is the effect of knocking out NHE3 in mice?
- Low plasma HCO3-
- Acidosis (low plasma pH)
- Slightly lower blood pressure
109
Which factor limits the maximum level of transport can occur?
Number of protein carriers in the membrane
110
What is the maximum reabsorption rate of glucose in the proximal tubule?
375 mg/min
111
Why do diabetes patients have glucose in their urine?
- Plasma glucose levels are too high due to inability to respond to insulin
- Means that 100% reabsorption of glucose in the kidneys can't be achieved
112
What substances are secreted by the proximal tubule (blood to tubular fluid)?
- Plasma protein bound substances
| - Foreign compounds e.g. penicillin
113
What occurs at the Loop of Henle?
Concentration of the urine
114
Where in the nephron do loop diuretics act?
Loop of Henle
115
What is reabsorbed at the Loop of Henle? (5)
- Na+
- Cl-
- Water
- Ca2+
- Mg2+
116
What are the 3 sections of the Loop of Henle?
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
117
What is reabsorbed at the thin descending limb?
Water
118
Which section of the Loop of Henle is water permeable?
Thin descending limb
119
What is reabsorbed at the thin ascending limb? (2)
- Na+
| - Cl-
120
What is reabsorbed at the thick ascending limb? (4)
- Na+
- Cl-
- Ca2+
- Mg2+
121
Which proteins are present in the basolateral membrane of the thick ascending limb epithelial cells? (3)
- Na+/K+ ATPase
- K+ channel
- CLCK (+barttin)
122
Which protein in the apical membrane transports Na+ and Cl- into the thick ascending limb epithelial cells?
NKCC2
123
What does NKCC2 transport?
- Na+
- 2Cl-
- K+
124
Where is NKCC2 found in the nephron?
Apical membrane of thick ascending limb cells
125
Which protein in the basolateral membrane transports Cl- into the blood from inside the cell in the thick ascending limb?
CLCK (+barttin)
126
Where in the nephron is CLCK found? (2)
Basolateral membrane of thick ascending limb cells and early distal tubule cells
127
How is Cl- absorbed into the blood at the thick ascending limb?
- 2Cl- cross the apical membrane via NKCC2
| - Cl- enters the blood via CLCK on the basolateral membrane
128
How is Na+ absorbed into the blood at the thick ascending limb?
- Crosses the apical membrane via NKCC2
| - Enters the blood via Na+/K+ ATPase on the basolateral membrane
129
How is absorption of Na+ and Cl- in the thick ascending limb important for water handling?
- No water reabsorption takes place in the thick ascending limb
- Ion reabsorption sets up an osmotic driving force for water reabsorption later on in the nephron
130
What is the beta/accessory subunit of CLCK?
Barttin
131
What is barttin?
Beta subunit of CLCK
132
How is K+ handled in the thick ascending limb cells?
- Enters via NKCC2 (apical)
| - Recycled by leaving via ROMK (apical) to provide enough K+ to support the function of NKCC2
133
Which proteins are present in the apical membrane of thick ascending limb cells? (2)
- NKCC2
| - ROMK
134
How are Ca2+ and Mg2+ absorbed in the thick ascending limb?
Follow the absorption of Na+ and Cl- via paracellular transport
135
Is Bartter's syndrome dominant or recessive?
Recessive
136
What are the symptoms of Bartter's syndrome? (7)
- Salt wasting
- Polyuria
- Hypotension
- Hypokalaemia
- Metabolic alkalosis
- Hypercalciuria
- Nephrocalcinosis
137
What is salt wasting?
Losing Na+ and Cl- in the urine that should've been absorbed from the tubular fluid
138
How does salt wasting cause polyuria?
- Reabsorption of Na+ and Cl- brings water with it via paracellular transport
- Less reabsorption of salt and water means more water in the urine i.e. higher urine flow rate
139
Why does polyuria cause hypotension?
Causes a decrease in extracellular fluid volume which leads to low blood pressure
140
What is hypokalaemia?
Low plasma potassium
141
What is hypercalciuria?
High levels of calcium in the urine
142
What causes Bartter's syndrome?
Mutations in NKCC2/ROMK/CLCK/Barttin (slightly different forms)
143
How does a mutation in NKCC2 cause Bartter's syndrome?
- No reabsorption of Na+ and Cl- = salt wasting
| - Salt wasting leads to polyuria, hypotension, hypercalciuria etc..
144
How does a mutation in CLCK cause Bartter's syndrome?
- Cl- enters via NKCC2 and accumulates in the cell (can't leave)
- High Cl- inside the cell causes NKCC2 to stop working
- No Na+ and Cl- reabsorption = salt wasting, polyuria, hypotension, hypercalciuria etc..
145
How does a mutation in Barttin cause Bartter's syndrome?
- CLCK can't work without Barttin
- Accumulation of Cl- stops NKCC2 working
- No Na+ and Cl- reabsorption = salt wasting, polyuria, hypotension, hypercalciuria etc..
146
How does a mutation in ROMK cause Bartter's syndrome?
- No recycling of K+, can only leave via the K+ channel on the basolateral membrane
- Not enough K+ in the tubular fluid to support function of NKCC2
- No Na+ and Cl- reabsorption = salt wasting, polyuria, hypotension, hypercalciuria etc.
147
Why do Bartter's patients have hypercalciuria?
- Calcium follows reabsorption of Na+ and Cl-
| - No Na+ and Cl- reabsorption in Bartter's syndrome so calcium remains in the tubular fluid
148
What is the fractional excretion value?
Amount of a substance in the urine out of the amount of the substance that was filtered
149
What does a fractional excretion value of 100% mean?
All of what was filtered at the glomerulus was excreted in the urine i.e. none of it was reabsorbed/secreted
150
What does a fractional excretion value of less than 100% mean?
Some of what was filtered was reabsorbed
151
What does a fractional excretion value of greater than 100% mean?
The substance has been filtered and then more has been secreted into the tubular fluid
152
What does a difference in the fractional excretion value between a wildtype and knockout organism indicate?
A tubule defect
153
What is the difference in symptoms between ROMK knockout mice and Bartter's patients?
- ROMK knockouts have salt wasting and polyuria like Bartter's patients
- ROMK knockouts have acidosis instead of alkalosis and no change in plasma K+ whereas Bartter's patients have hypokalaemia
154
What are 2 examples of loop diuretics?
- Furosemide
| - Bumetanide
155
How do loop diuretics work?
Inhibit NKCC2 in the thick ascending limb
156
What are loop diuretics used to treat?
Hypertension
157
How do loop diuretics treat hypertension?
- Inhibit Na+ and Cl- absorption via NKCC2
- Therefore less water is reabsorbed
- Decreases extracellular fluid volume
158
What are the side effects of loop diuretics?
- Bartter's-like symptoms
| - i.e. plasma K+ issues, pH issues, calcium issues
159
What is reabsorbed at the early distal tubule?
- Na+
- Cl-
- Mg2+
160
What are the 2 types of diuretics?
- Loop diuretics
| - Thiazide diuretics
161
Where in the nephron do thiazide diuretics act?
Early distal tubule
162
Which proteins are present in the basolateral membrane of the early distal tubule cells? (3)
- Na+/K+ ATPase
- K+ channel
- CLCK (+barttin)
163
Which proteins are present in the apical membrane of the early distal tubule cells? (2)
- NCC
| - Mg2+ channels
164
What does NCC transport?
- Sodium/chloride cotransporter
| - 1 Na+ and 1 Cl-
165
How is magnesium absorbed into the blood across the basolateral membrane from the early distal tubule?
Unknown pathway
166
Is Gitelman's syndrome dominant or recessive?
Recessive
167
What are the symptoms of Gitelman's syndrome? (6)
- Salt wasting
- Polyuria
- Hypotension
- Hypokalaemia
- Metabolic alkalosis
- Hypocalciuria
168
What is the difference in symptoms between Bartter's and Gitelman's syndrome?
Bartter's patients have hypercalciuria and nephrocalcinosis but Gitelman's patients have hypocalciuria
169
Where in the nephron are the mutations for Bartter's syndrome?
Thick ascending limb
170
Where in the nephron are the mutations for Gitelman's syndrome?
Early distal tubule
171
What causes Gitelman's syndrome?
Mutation in NCC
172
Where in the nephron is ROMK located? (2)
- Apical membrane of thick ascending limb cells
| - Apical membrane of principal cells in the late distal tubule and cortical collecting duct
173
Where in the nephron is NCC located?
Apical membrane of early distal tubule cells
174
What specific mutations in NCC are seen in Gitelman's patients? (2)
- Glycine 627 valine
| - Arginine 935 glutamine
175
How do mutations in Gitelman's cause loss of function of NCC?
Less NCC is trafficked to the membrane so there are fewer NCCs in the apical membrane of early distal tubule cells
176
How do thiazide diuretics work?
Inhibit NCC in the early distal tubule
177
What is an example of a thiazide diuretic?
Chlorothiazide
178
What are thiazide diuretics used to treat?
Hypertension
179
What are the side effects of thiazide diuretics?
Gitelman's-like symptoms
180
What does carrying one mutation for ROMK/NCCK2/NCC (Bartter's/Gitelman's) potentially cause?
Protection against hypertension
181
What are the connecting tubules?
Connects the late distal tubule to the cortical collecting duct
182
Which processes occur in the late distal, connecting tubules and the cortical collecting duct? (3)
- Concentration of the urine
- Reabsorption of Na+ and water
- Secretion of K+ and H+ into the urine
183
What are the 2 cell types in the distal tubule and the cortical collecting duct?
- Principal cells
| - Intercalated cells
184
What is the function of the principal cells? (2)
- Na+ and water reabsorption
| - K+ and H+ secretion into the urine
185
Where in the nephron are principal cells found? (2)
Late distal tubule and cortical collecting duct
186
Where in the nephron are intercalated cells found? (2)
Late distal tubule and cortical collecting duct
187
What are the 2 types of intercalated cells?
Alpha and beta
188
What is the function of the alpha intercalated cells? (2)
- H+ secretion
| - HCO3- reabsorption
189
What is the function of the beta intercalated cells? (2)
- H+ and Cl- reabsorption
| - HCO3- secretion
190
Which proteins are in the apical membrane of principal cells? (3)
- ENaC
- ROMK
- Aquaporin 2
191
Which proteins are in the basolateral membrane of principal cells? (3)
- Na+/K+ ATPase
- K+ channel (Kir2.3)
- Aquaporins (AQP3 and AQP4)
192
Where in the nephron is aquaporin 2 found?
Apical membrane of principal cells in the late distal tubule and cortical collecting duct
193
Which type of aquaporin is found on the apical membrane of principal cells?
Aquaporin 2
194
How is Na+ reabsorbed by the principal cells?
- Enters via ENaC on the apical membrane
| - Leaves via Na+/K+ ATPase
195
How is water reabsorbed by the principal cells?
- Enters via aquaporin 2
| - Leaves via aquaporins 3 and 4
196
Which types of aquaporin are found on the basolateral membrane of principal cells? (2)
- AQP3
| - AQP4
197
Where in the nephron are AQP3 and 4 found?
Basolateral membrane of principal cells in the late distal tubule and collecting duct
198
Where in the nephron is ENaC found?
Apical membrane of principal cells in the late distal tubule and collecting duct
199
Which protein in the principal cells transports Na+ into the cell?
ENaC
200
Which type of K+ channel is found in the basolateral membrane of the principal cells?
Kir2.3
201
Why do Bartter's and Gitelman's syndrome patients have hypokalaemia?
- Tubular fluid with high Na+ content reaches the principal cells and more Na+ is reabsorbed through ENaC than usual
- More K+ than usual is secreted and lost in the urine via ROMK so plasma K+ is lower than usual (hypokalaemia)
202
Why do Bartter's and Gitelman's syndrome patients have metabolic alkalosis?
- Tubular fluid with high Na+ content reaches the principal cells and more Na+ is reabsorbed through ENaC than usual
- More Na+ reabsorption means more H+ secretion into the urine so pH of body fluids are too high (alkalosis)
203
What is Diabetes Insipidus?
Patient's struggle to reabsorb water due to issues with aquaporin 2 so have an extremely high urine flow rate
204
What inherited conditions can arise from issues with the principal cells? (3)
- Diabetes Insipidus
- Liddle's syndrome
- Pseudohypoaldosteronism
205
Which protein is not working correctly in Diabetes Insipidus?
Aquaporin 2 in the apical membrane of principal cells in the late distal tubule and cortical collecting duct
206
What is Liddle's syndrome?
Too much Na+ absorbed via ENaC and then too much water reabsorbed with it causing severe hypotension
207
What causes Liddle's syndrome?
Gain of function mutation in ENaC in the apical membrane of principal cells in the late distal tubule and cortical collecting duct
208
What kind of drug is amiloride?
Diuretic
209
What is amiloride used to treat?
Hypertension
210
How does amiloride work?
- Inhibits ENaC in the principal cells
| - Patients lose Na+ and water in their urine
211
Which proteins are in the apical membrane of alpha intercalated cells? (1)
Proton ATPase (i.e. H+ pump)
212
Which proteins are in the basolateral membrane of alpha intercalated cells? (2)
- AE1
| - Cl- channel
213
How do alpha intercalated cells secrete H+?
H+ pumped into the tubular fluid via the proton ATPase on the apical membrane
214
How do alpha intercalated cells reabsorb HCO3-?
- HCO3- inside the cells enters the blood via AE1 in exchange for Cl-
- Cl- taken into the cell is recycled via the Cl- channel
215
Where in the nephron is AE1? (2)
- Basolateral membrane of alpha intercalated cells
| - Apical membrane beta intercalated cells
216
Which proteins are in the apical membrane of beta intercalated cells?
AE1
217
Which proteins are in the basolateral membrane of beta intercalated cells? (2)
- Proton ATPase
| - Cl- channel
218
How do beta intercalated cells reabsorb H+ and Cl-?
- H+ pumped into the blood via the proton ATPase on the basolateral membrane
- Cl- enters via AE1 on the apical membrane and enters the blood via the Cl- channel on the basolateral membrane
219
How do beta intercalated cells secrete HCO3-?
HCO3- is pumped into the tubular fluid via AE1 in exchange for Cl- which enters the cell
220
How do intercalated cells help the body adjust to changing pH?
Can transition between alpha and beta by moving proteins around to secrete/retain H+
221
What are the features of the medullary collecting duct? (2)
- Low Na+ permeability
| - High water and urea permeability in the presence of vasopressin
222
What is the function of aldosterone?
Regulates Na+ and K+ reabsorption in the late distal tubule and collecting duct
223
What is the function of vasopressin?
Regulates water reabsorption in the collecting duct
224
How much of the Na+ that is filtered from the blood is reabsorbed?
99%
225
How much of the water that is filtered from the blood is reabsorbed?
99%
226
What is acute renal failure?
Fall in glomerular filtration rate over hours/days (very short time period)
227
What is the treatment for acute renal failure?
Dialysis
228
What are the symptoms of acute renal failure? (4)
- Hypervolaemia
- Hyperkalaemia
- Acidosis
- High urea and creatinine (nitrogenous waste=toxic)
229
What is hypervolaemia?
Expansion of the extracellular fluid volume
230
What is oliguria?
Low urine output
231
Why do acute renal failure patients have hypervolaemia?
Low GFR so oliguria so extracellular fluid volume increases because water not being secreted in the urine
232
Why do acute renal failure patients have hyperkalaemia?
Oliguria so lack of K+ secretion
233
What results from hyperkalaemia?
- Increased cardiac excitability
| - Can cause sudden cardiac death
234
Why do acute renal failure patients have acidosis?
Oliguria so lack of H+ secretion
235
What results from acidosis?
Depression of the CNS
236
What results from inability to excrete nitrogenous waste (urea/creatinine)? (2)
- Impaired mental function
| - Nausea/vomiting
237
What could be a pre-renal cause of acute renal failure?
Hypotension
238
How could hypotension cause acute renal failure?
Loss of blood causing hypotension results in poor renal perfusion which means not much glomerular filtration is occurring and urine output is low
239
What is rhabdomyolysis?
Release of myoglobin from damaged muscle
240
What could be a renal cause of acute renal failure?
Rhabdomyolysis
241
How could rhabdomyolysis cause acute renal failure?
Myoglobin is released and has toxic effects on the kidney tubules
242
Which ion has the highest concentration in the intracellular fluid compartment?
K+
243
What does low plasma HCO3- indicate?
Acidosis
244
Why does low HCO3- indicate acidosis?
High levels of H+ ions combine with HCO3- in the body fluids resulting in low HCO3-
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Why can IV saline be used to treat hyperkalaemia?
Dilutes the plasma K+ to bring it back down to normal
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Where is vasopressin released?
- Made in the cell bodies of neurons in the hypothalamus whose axons project into the posterior pituitary
- Vesicles containing vasopressin released from posterior pituitary in response to an action potential
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What does vasopressin regulate?
Osmolality
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What is osmolality?
- Concentration of dissolved solutes in a solution
| - High osmolality = lots of salt
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When is vasopressin released?
- When body wants to conserve water
| - In response to high plasma osmolality
250
What are the units of osmolality?
mosmol/kg of water
251
What is normal plasma osmolality?
270-300 mosmol/kg water
252
Where are osmoreceptors located?
In the supraoptic and paraventricular nuclei of the hypothalamus
253
What happens when plasma osmolality increases?
- Osmoreceptors in hypothalamus are stimulated
- Action potentials in neurosecretory neurons in hypothalamus causes vasopressin release from posterior pituitary
- Less water released and feeling of thirst
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What external factors can stimulate vasopressin release? (3)
- Stress
- Nicotine
- Ecstasy
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What external factors can inhibit vasopressin release? (2)
- Excessive fluid ingestion
| - Alcohol consumption
256
How does increased vasopressin affect principal cells?
- Binds to V2 receptors on the basolateral membrane
- Activates PKA which causes fusion of vesicles containing AQP2 with the apical membrane
- More water can be reabsorbed through the AQP2 channels
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What happens to principal cells when vasopressin is low?
AQP2 channels pulled out of the apical membrane
258
What is the net effect of vasopressin release?
- Increased reabsorption of water so decreased secretion in urine
- Fall in body fluid osmolality
259
How much urine can Diabetes Insipidus patients secrete per day?
23 litres
260
What is Central Diabetes Insipidus?
Patient doesn't release vasopressin
261
How is Central Diabetes Insipidus treated?
Nasal spray containing synthetic vasopressin
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What is Nephrogenic Diabetes Insipidus?
Patients can't respond to vasopressin
263
What are the 2 types of Diabetes Insipidus?
- Central Diabetes Insipidus
| - Nephrogenic Diabetes Insipidus
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What can cause Nephrogenic Diabetes Insipidus? (2)
- Defect in V2 receptor
| - Defect in AQP2 channels
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Where is aldosterone released?
Zona glomerulosa layer in the cortex of adrenal gland
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What kind of hormone is aldosterone?
Mineralocorticoid
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What does aldosterone regulate?
Plasma Na+, K+ and body fluid volume
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When is aldosterone released? (3)
- Rise in plasma K+
- Fall in plasma Na+ (minor regulation)
- Fall in extracellular fluid volume
269
Where does aldosterone act? (2)
- Late distal tubule
| - Collecting duct (both principal and intercalated cells)
270
What is the effect of aldosterone release? (3)
- Increased reabsorption of Na+
- Increased reabsorption of water (follows Na+)
- Increased secretion of K+ and H+
271
What is the genomic action of aldosterone in principal cells?
- Diffuses across lipid membrane and binds to cytosolic receptors
- Complex moves into the nucleus
- Stimulates transcription and synthesis of proteins involved in Na+ reabsorption, K+ and H+ secretion
- I.e. ENaC, ROMK, Na+/H+ exchanger, Na+/K+ ATPase, H+ ATPase
272
What is the non-genomic action of aldosterone in the principal cells?
- Increased activity of ENaC
| - Much faster than genomic action
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What does Liddle's syndrome cause? (3)
- Hypertension
- High Na+ reabsorption but low aldosterone
- Too many Na+ channels in the principal cells
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How is Liddle's syndrome treated?
Amiloride (blocks ENaC to reduce Na+ reabsorption, diuretic)
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What does pseudohypoaldosteronism cause? (3)
- Salt loss but high aldosterone
- Loss of response to aldosterone
- Mineralocorticoid receptor defect
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What does the renin-angiotensin system regulate?
Plasma Na+, K+ and body fluid volume (same as aldosterone)
277
How is the renin-angiotensin cascade initiated?
- Decrease in extracellular fluid volume
- Renin released from JGA
- Catalyses production of angiotensin I from angiotensinogen
- Angiotensin I converted into angiotensin II by ACE (active form)
278
What is the JGA?
Juxtaglomerular Apparatus
279
What are macula densa cells?
Detect changes in composition and flow rate of the tubular fluid in the early distal tubule and send signals to glomerular capillaries
280
What are granular cells?
Renin-containing cells
280
Where is angiotensinogen produced?
Liver
281
What is ACE?
Angiotensin Converting Enzyme
282
Where is ACE found?
Capillaries
283
What is the active form of angiotensin?
Angiotensin II
284
Where is the most angiotensin II produced?
In the lungs due to the high density of capillaries
285
Where does angiotensin II act?
Zona glomerulosa
286
What does angiotensin II do? (2)
- Promotes the release of aldosterone from the zona glomerulosa
- Causes vasoconstriction of arterioles to increase blood pressure
287
Where is aldosterone released from?
Zona glomerulosa in the kidneys
288
What is the net effect of angiotensin II? (3)
- Increased Na+ reabsorption
- Increased extracellular fluid volume
- Increased blood pressure
289
What happens when your angiotensin II levels are too high?
- Hypertension
- Excess aldosterone
- Na+ and water retention
290
How do you treat hypertension caused by increased angiotensin II levels?
ACE inhibitors
291
Is extracellular fluid volume or plasma osmolality more important?
- Extracellular fluid volume
- Body can accommodate changes in osmolality by resetting the vasopressin system (not the aldosterone system) to favour ECFV which is more critical (blood pressure)
