Anatomy and physiology Flashcards
(395 cards)
1
Q
What are the components of the urinary system?
A
Kidneys
Ureter
Urinary bladder
Urethra
2
Q
What are the functions of the urinary system?
A
Removes metabolic waste (filtration and excretion) Regulates plasma electrolytes and BP Stabilise pH Reabsorption of small molecules Produces erythropoietin
3
Q
What is erythropoietin?
A
Released by kidney
Stimulant of RBC production by bone marrow
4
Q
How is the kidney peritonised?
A
Retroperitoneal
5
Q
At what level are the kidneys found?
A
T12-L3
6
Q
What kidney is lower?
A
Right
7
Q
What plane crosses at L1?
A
Transpyloric plane
8
Q
What organs are directly attached to organ (partially peritonised)?
A
Colon
Duodenum
Pancreas
Suprarenal glands
9
Q
What are the posterior relations of the kidney?
A
12th rib
10
Q
How are kidneys accessed in surgery?
A
Through back
11
Q
What nerves are behind the kidney?
A
Subcostal
Ileohypogastric
Iliolingual
12
Q
What CT covers the kidney?
A
Renal capsule
13
Q
What are the layers of capsule and fascia surrounding the kidney?
A
Renal capsule
Perirenal fat
Renal fascia
Pararenal fat
14
Q
How many pyramids are in the medulla?
A
10-18
15
Q
What structures form the medulla to ureter?
A
Pyramid –> papilla –> minor calyx –> major calyx –> pelvis –> ureter
16
Q
What is present in the papilla?
A
Collecting ducts
17
Q
How many constrictions are there in the ureter?
A
Renal inferior pole (Abdo)
Crosses over external iliac vessels (pelvic)
Transverse bladder wall (intramural)
18
Q
Wear are the constrictions of the ureter clinically important?
A
Potential location of kidney stones
19
Q
What vessels is most anterior at hilum?
A
Vein (VAP)
20
Q
What vessel is most superior at hilum?
A
Artery
21
Q
How many segments are in the kidney?
A
5
22
Q
What is the branching pattern of renal arteries?
A
Segmental –> interloper –> arcuate – > interlober
23
Q
Where do the renal veins drain?
A
Inferior vena cava
24
Q
Where does lymph from kidneys drain?
A
Lateral aortic lymph nodes
25
What is the nerve supply to the renal plexus?
SNS = T10-L1
| Sensory afferent = T11-L2
26
Where is the trigone?
Posterior surface
27
What is the type of epithelium found in the bladder?
Transitional
28
When doing abdo ultrasound of uterus, why does the patient need to drink lots of water?
Uterus below pelvic brim (lots of water pulls up bladder and uterus)
29
What is the median umbilical ligament?
Embryonic urachus
30
Where are the two inferior epigastric vessels from?
Two lateral umbilical folds
31
What are the embryonic remnants of the two medial umbilical folds?
Occluded umbilical artery
32
How is the bladder peritonised?
Only at superior part
33
What is the name of the pouch that sits posterior to bladder and has ?
Such of Douglas (retrouterine)
34
What nerve opens the external urethral sphincter?
Pudendal (S2,3,4) - somatic control
35
What is the PNS supply to the bladder?
Pelvic splanchnic nerves (S2,3,4)
36
What is the spongy/longest part of the urine?
Penile
37
What is the most dilated part of the urethra?
Prostatic
38
Which sphincter is involuntary?
Internal
39
What part of the urethra is the narrowest?
Membranous part
40
Which nerve constricts detrusor muscle during micturition?
Parasympathetic
41
Which nerve constricts the internal urethral sphincter during ejaculation?
Sympathetic
42
Which is the narrowest part of the urethra in male?
Membranous
43
What vertebral level is the transpyloric plane located?
L1
44
What structures are located in the nephron?
Renal corpuscle + renal tubules
45
What structures are present in the renal corpuscles?
Glemerulus + bowmen's capsule
46
What constitutes the uriniferous tubule?
Nephron + collecting duct
47
What is the function of proximal convoluted tubule?
Reabsorption
48
What epithelium is present in the ureter?
Transitional
49
Where will you see a star shaped lumen?
Ureter
50
What is proteinuria a sign of?
Kidney disease
51
What are markers of kidney disease in blood?
GFR down
Urea up
Creatinine up
52
What layer of the embryo forms the urinary system?
Mesoderm (intermediate plate)
53
What is found at the top of the cloaca?
Allantois
54
Where does the allantois come from?
Hindgut
55
What does the cloaca divide to form?
Rectum (post) + Urogenital sinus (ant)
56
What drains into the urogenital sinus?
Mesonephric duct
57
What does the urogenital sinus later form?
Urinary bladder and caudal end forms urethra
58
When does allantois disappear?
When cord is cut
59
What vessels comes form the internal iliac and supplies the posterior surface of the bladder?
Superior vesical artery
60
When does the pronephros form?
Week 4
61
What does the pronephros form from?
Intermediate mesoderm
62
How many sets of kidneys are formed sequentially during nephrogenesis?
3
63
Pronephros degenerates except form the duct which forms?
The mesonephric duct.
64
When does the pronephros degenerate?
Week 5 (except the duct)
65
When does the metanephros develop?
Week 5
66
When does the metanephros begin to function?
Week 9
67
When does the mesonephros form?
Late week 4
68
How long does the mesonephros function as the kidney for?
Approx. 4 weeks
69
What happens to the mesonephros?
Incorporated into gonad
70
What do the mesonephric tubules in males become?
The rete testis
71
What does the mesonephric duct become in males?
Vas deferens
72
What happens to the mesonephros in females?
Becomes ovaries (tubules and duct degenerate)
73
What is a nephron?
Renal corpuscle + PCT + loop of Henley + DCT
74
What is a uriniferous tubule?
Nephron + collecting duct
75
Describe the ascent of kidneys?
Due to differential growth of lower body inferiorly
Hilum rotates 90 degrees ventral to medial.
STOP when in contact with adrenal glands
76
Where does the mesonephric duct drain?
Cloaca
77
Where does the ureteric bud grow form?
Caudal end of mesonephric duct --> branch to form renal pelvis, calyces and collecting ducts
78
What structures reciprocal induce each other?
Ureteric bud and metenephric mesoderm
79
What are the key functions of the kidney?
1. Filtration (20% of plasma filtered out)
2. Reabsorption (e.g glucose)
3. Secretion (e.g drug metabolites)
80
What is the average glomerular filtration rate?
180 l/day (125 ml/min)
81
Where does reabsorption start?
Proximal tubule and distal tubule
82
What % of blood flow does the kidneys receive from CO?
20-25% (1.2l/min)
83
What is the renal plasma flow?
660ml/min
84
What is the filtration fraction of the renal plasma becomes glomerular filtrate/
19%
85
What is glomerular filtration dependent on?
STARLING'S FORCES:
Hydrostatic forces (favour filtration)
Oncotic pressure forces (favour reabsorption)
86
What anatomical features of the bowman's capsule assists with filtration?
```
Fenestration
Basal lamina (prevents large particles)
Slit membrane (prevents medium particles)
```
87
Why is the glomerular afferent capillary pressure higher than most capillaries?
Short, wide, little resistance to flow (high hydrostatic pressure)
88
How does kidney increase or decrease glomerulus pressure to control filtration rate?
Hydrostatic pressure upstream increased --> high resistance
89
What contributes to the very high PGC?
Afferent and efferent arterioles
90
What is favoured at glomerular capillaries for filtration?
Hydrostatic pressure exceeds oncotic pressure
91
What is the net filtration pressure?
10mmHg
92
What affects GFR?
1. If pressure rises --> GFR increases
| 2. Diameter of afferent and efferent arterioles
93
What extrinsically controls GFR?
Sympathetic VC nerves
Circulating catecholamines
Angiotensin II
94
What happens if efferent arterioles are constricted?
Increased GFR
95
What happens if afferent arterioles are constricted?
Decreased GFR
96
In man, autoregulation of blood flow and GFR is present in kidneys over what range of MBP?
60-130mmHg
97
At what MBP does auto regulation of filtration fail?
50mmHg
98
In situations where BV/BP faces serious compromise e.g in haemorrhage, what overrides autoregulation?
Sympathetic VC
99
How much blood can be provided to perfuse other organs at expense of kidneys?
800ml
100
What capillaries are responsible for reabsorption?
Peritubular capillaries
101
Why does the oncotic gradient go up driving reabsorption in peritubular capillaries?
Large pressure drop in hydrostatic pressure, oncotic pressure higher since plasma volume reduced by approx 20% and higher concentration of plasma proteins
102
What is reabsorbed into the tubule?
99% water
100% glucose
99.5% Na+
50% urea
103
What is reabsorption mediated by?
Carrier mediated transport proteins (aquaporins)
104
What happens when the maximum transport capacity of the carriers are saturated?
Excess substrate enters urine
105
What is the renal threshold in relation to carrier proteins?
Plasma threshold at which saturation occurs
106
Give an example of when the renal threshold is reached.
Glucose transport in diabetes (Tm mechanism saturated)
107
Up to what concentration of blood glucose is reabsorbed?
10mmol/l.
Therfore, if 15mmol/l, 5 mol/l will be excreted in kidneys
108
If we have 20mmol/l of glucose in blood, how much is filtered?
20mmol/l
109
Name two substances that have a Tm higher than normal levels so excretion doesn't occur (control mechanism)?
Glucose
| AAs
110
Name two substances that are regulated by the kidney by means of the Tm mechanism (regulated to the normal).
Sulphate ions
| Phosphate ions
111
What is the most important/abundant reabsorption process in kidney?
Na+ ions
112
Where does the majority of Na+ ion reabsorption occur?
Proximal tubule (brush border has higher permeability to Na+)
113
What mechanism allows Na+ reabsorption?
Active transport (establishes gradient)
114
Where are active Na+ pumps located?
Basolateral surfaces
115
What is required to pump Na+ out?
Active transport ATP driven (pumps out Na+, generating gradient and moving cells passively across the luminal membrane)
116
Why is the brush border of the proximal tubule more permeable to Na+?
Large SA
| Large number of Na+ channels
117
By actively transporting Na+, what else is generated?
Water transport across membrane (osmotic equivalent) --> greater concentration gradient (allow flow of other ions)
118
What causes the Cl- to diffuse passively across the proximal tubular membrane?
Down the electrochemical gradient established by Na+ transport
119
What does the rate of reabsorption of non-actively reabsorbed solutes depend on?
1. Amount of water removed
| 2. Permeability of membrane to that substance
120
What substance is the tubular membrane only moderately permeable to?
Urea
121
Name two substances that the tubular membrane is impermeable to.
Insulin
| Mannitol
122
Give an example of a symporter?
For each molecule of Na+, also transport molecule of glucose.
123
Discuss the transport of glucose if low [Na+]?
Low glucose reabsorption
124
What mechanism is used for secretion from peritubular capillaries back into collecting tubule?
Tm - limited carrier-mediated secretory mechanisms
125
What molecules are secreted into the tubule?
```
Penicillin
Aspirin
Para-amino-hippuric acid
Lactic acid
Uric acid
```
126
What does hypokalaemia cause?
Arrhythmias and death
127
What does hyperkalaemia cause?
VF and death
128
What is the normal ECF [K+]?
approx 4 mmol/l
129
What regulates K+ secretion?
Aldosterone
130
What does aldosterone stimulate in relation to K+?
Increases renal tubule cell K+ secretion
131
In addition to K+, what does aldosterone stimulate?
Na+ reabsorption
132
Where are H+ ions actively secreted?
From tubule cells not peritubular capillaries
133
What organ metabolises non polar/lipid-soluble drugs to facilitate reabsorption in kidneys?
Liver
134
Discuss osmolarity of fluid in proximal tubule and plasma.
Isosmotic (300mOmoles/l)
135
Why is osmolarity of fluid in proximal tubule and plasma isosmotic?
Accompanied by equivalent water molecules
136
What system is essential for water balance?
Juxtamedullary nephrons at loop of Henle
137
What is the maximum concentration of urine that can be produced?
4 x more concentrated than plasma
138
What is the minimum obligatory water loss?
500mls/day
139
Why is there a minimum obligatory water loss?
Urea, phosphate and other waste products and non-waste products (Na+ and K+) need to be secreted
140
What allows the kidneys to produce urine of varying concentrations?
Loops of Henle of juxtamedullary nephrons act as counter-current multipliers
141
What is the function of the ascending limb?
Actively co-transports Na+ and Cl- out of tubule lumen
142
What is the ascending limb impermeable to?
Water
143
What is the descending limb permeable to?
Water
144
What is the descending limb impermeable to?
NaCl
145
What gradient is produced by active transported in loop of henle?
200mOsm
146
What is the osmolarity of the loop of Henle?
Isosmotic (approx. 300m0sml/l)
147
What is the key step in the loop of Henle?
Active removal of NaCl from ascending limb
148
What does an increased concentration in the interstitium result in?
More water secreted
| --> loop more concentrated
149
At any horizontal level, what is the gradient between the ascending limb and interstitium?
200mOsmol
150
What is the 200mOsmole gradient as a result from?
Pumping of active pumps
151
Give an example of a blocker of active transport of NaCl out of the ascending limb in the loop of henle?
Frusemide
152
How does frusemide work?
Blocker active transport of NaCl out of the ascending limb in the loop of Henle --> isotonic urine
153
What percentage of the initial volume of additional water is reabsorbed by countercurrent multiplier in loop of Henle?
15-20% (36L)
154
Why is the countercurrent multiplier significant?
- Increases concentration in interstitium
| - Delivers hypotonic fluid to distal tubule
155
What is the function of the Vase Recta?
1. Provides O2 for medulla
2. O2 must not disturb gradient
3. Remove excess water (countercurrent exchanger) --> equilibrate with the medullary interstitial gradient
156
Discuss the flow rate through the vasa recta.
Very low --> plenty of time for equilibration
157
What is urine osmolarity dependent on?
Reabsorption in collecting duct
158
Where is the main site of water regulation?
Collecting duct
159
What controls the permeability of the collecting duct?
ADH (Vasopressin)
160
What is the half-life of ADH?
Approx 10 mins
161
What is the primary control of plasma osmolarity?
ADH
162
What nuclei synthesis ADH?
Supraoptic and paraventricular nuclei
163
What happens to osmoreceptors when osmolarity increases?
Water out of cells
| --> cells shrink --> neural discharge form nuclei --> ADH secretion
164
What happens to osmoreceptors when osmolarity decreases?
Water in to cells
| --> cells swell --> decreased neural discharge from nuclei --> decreased ADH secretion
165
What is the normal plasma osmolality?
280-290mOsm/kg water
166
For a 2.5% increase is osmolality, how much does the concentration of ASH increase by?
10x
167
In addition to an increase is osmolarity, what else needs to occur to increase ADH?
Tonicity
168
What is the difference between osmolarity and tonicity?
```
Osmolarity = solute concentration/unit volume of solvent
Tonicity = osmotic pressure gradient between two solutions
```
169
What kind of channels are osmoreceptors?
Stretch sensitive
170
What solutes don't produce "osmotic drag" or tonicity?
Solutes that can penetrate membranes move together with water
171
If osmolarity increases (water moves out), what happens to the [NaCl]?
Increases
172
As a result of increased osmolarity and increased [NaCl] what happens to ADH?
Increases
173
What happens to urea when osmolarity increases?
Urea increases
174
When osmolarity and urea increase , what happens to the volume and ADH?
No change in volume, discharge or ADH release
175
Name an ineffective osmole.
Urea
176
Why does urea not cause increase in ADH?
Tonicity (osmotic pressure gradient doesn't exist)
177
What happens after ingestion of hypertonic solutions (e.g seawater)?
Increases solute load to be excreted --> dehydration
178
What does urine osmolarity depend on ?
Reabsorption in collecting ducts
179
What is the function of the collecting duct?
Site of water regulation
180
What controls the permeability of the collecting duct?
ADH
181
How does vasopressin work?
Bind to membrane receptor --> activates cAMP --> cell inserts AQP2 water pores into apical membrane --> water absorbed by the blood by osmosis
182
What does ADH do to the collecting ducts to increase permeability?
Incorporate aquaporins into luminal membrane of collecting duct
183
If ADH is present, what two areas are equilibrated at 30mOsml/l?
cortical collecting duct and cortical interstitium
184
If maximum ADH, what do the contents of the cortical collecting duct equilibrate with?
Medullary interstitium (highlights concentrated at tip of medulla)
185
What kind of urine is produced with maximal [ADH]?
Small volume and highly concentrated
186
In water deficit, where is water reabsorbed?
In vasa recta (high oncotic pressure)
187
If ADH was absent, what happens to the collecting ducts and urine?
Impermeable to water --> large volume of dilute urine excreted (compensating for water excess)
188
What is the role of urea?
Production of concentrated urine
189
When does urea tend to move out of collecting ducts?
Medullary tips
190
What enhances the permeability of the late medullary collecting duct to urea?
ADH
191
What happens in anti-diuresis with high levels of ADH?
Urea is retained in order to save water and reinforce medullary gradient in region of thin ascending limb of LoH (URAEMIA occurs)
192
Why should urea be reabsorbed?
If retained in tubule , osmotic effect to hold water in tubule therefore, unable to rehydrate
193
How does ECF control ADH?
If increase in ECF --> decrease [ADH]
If decrease in ECF --> increase [ADH]
194
Where are low pressure receptors located?
L & R atria and great veins
195
Where are high pressure receptors located?
Carotid and aortic arch baroreceptors
196
If ECF decreases, what happens to stretch receptor firing and ADH secretion?
Decrease atrial receptor discharge and therefore, increase ADH
197
What happens to ADH as a result of volume expansion?
Decrease ADH
198
What increases ADH?
```
Emotion
Stress
Exercise
Nictotine
Morphine
After traumatic surgery
```
199
What suppresses ADH?
Alcohol
200
Describe how exercise increases ADH.
Need reabsorption to prevent dehydration
201
In what condition is there an ADH deficiency?
Diabetes Insipidus
202
What is the average volume of fluid secreted as urine each day/
1.5L/day
203
What is the range of osmolarity of fluid at the end of the collecting duct?
50-1200mOsm
204
What is one of the most important aspects of the ECF regulated by the kidney?
Volume
205
What are the key ECF ions?
Na+ and Cl-
206
What are the key ICF ions?
K+
207
How can the ECF be controlled?
By regulating Na+
208
What % of 60% of the TBW is found in the ICF?
75%
209
What constitutes the ECF?
Plasma + interstitial fluid
210
In litres, what is the distribution of water in the ICF and ECF?
```
ECF = 14L (plasma = 3, interstitial = 11)
ICF = 28L
```
211
What does increasing Na+ content in ECF do?
Increase ECF content, increase plasma volume perfusing tissues, increased BP
212
What is the renal response to a decrease in ECF?
Hypovolaemia
213
Discuss hypovolaemia form salt and water loss.
Decrease plasma volume -> decrease venous pressure -> decrease in venous return -> decrease EDV -> decrease SV, CO, BP -> increase SNS discharge to increase VC, TPR and BP
214
What is the bodies response to hypovolaemia?
1. Increase SNS discharge to increase VC, TPR and BP
| 2. More release of ADH (to reabsorb more water from filtrate)
215
The SNS causes systemic vasoconstriction including in the renal artery vasoconstriction. What does this cause?
Increase renin
| -> increase angiotensin II -> increase aldosterone
216
Where does angiotensin II act?
Proximal tubule (increase reabsorption)
217
Where does aldosterone act?
Distal tubule
218
What drives the reabsorption?
Oncotic pressure
219
What happens to the oncotic pressure in hypovolaemia?
Increases
220
What is the effect of oncotic pressure during hypovolaemia on GFR?
Largely unaffected - stays constant. Compensating for less volume by maintaining pressure between afferent and efferent.
221
When will GFR not be able to be maintained?
Until volume depletion severe enough to cause considerable decrease in MBP.
222
Discuss Starling's forces in relation to hypervolaemia.
Hydrostatic pressure increased
| Oncotic pressure decreased
223
How is Na+ reabsorption regulated at distal tubule?
Aldosterone
224
What forms the juxtaglomerular apparatus?
Juxtaglomerular cells and macula densa
225
What cells produce the hormone renin?
Juxtaglomerular cells
226
What is the only rate limiting step in the production of angiotensin II?
Renin
227
What converts angiotensin I to angiotensin II?
ACE
228
Where does the greatest proportion of the conversion of angiotensin I to angiotensin II occur?
As blood passes through pulmonary circuit.
229
What does angiotensin II act on?
```
Arterioles (vasonconstrict)
CV control centre in medulla oblongata (Increase CV response)
Hypothalamus (increase ADH)
Adrenal cortex (increase aldosterone)
```
230
What is the function of aldosterone?
Increase Na+ reabsorption in distal tubule
231
What are the overall responses of Angiotensin II?
Increase BP
| Increase volume and osmolarity
232
What controls renin release?
1. When pressure in afferent arteriole at level of JG cells decreases
2. Increse SNS causes increase renin (b1 effect)
3. Decrease in NaCl delivery
233
What do JG cells act as?
"Renal baroreceptors", less distension = increases renin
234
If NaCl delivery decreases , what will result?
Increase renin
235
What inhibits renin release?
ADH
236
In hypovolaemia, what helps to restore volume deficits?
Increase proximal and distal Na+ reabsorption + osmotic effects of water
237
Why is angiotensin II important in body's response to hypovolaemia?
1. Stimulates aldosterone
2. Potent vasoconstrictor
3. Stimulate ADH secretion
4. Stimulates thirst
238
What does tubuloglomerular feedback contribute to?
GFR constancy
239
Discuss tubuloglomerular feedback?
Filter more --> increased flow through macula dense (increased salt delivery) --> paracrine affect constricting afferent arterioles --> reduce GFR
240
If a person suffers from severe diarrhoea who has lost 3L of salt and water and trys to compensate by drinking 2L of pure water. What happens?
Hyposmotic and hypovolaemic
Decrease ECF osmolarity --> inhibits ADH
Decrease volume --> increase ADH via baroreceptors
* Priority = volume
241
Does hypovolaemia or hyposmolarity have priority?
Hypovolaemia (affect BP)
242
When is osmolarity not the main dependent of [ADH]?
Sufficient volume change to compromise brain perfusion
243
What should be done to restore volume in acute hypovolaemia (e.g haemorrhage)?
0.9% NaCl (saline) infusion
244
What is the antagonist for aldosterone?
ANP (atrial natriuretic peptide)
245
What is the function of ANP?
Promotes Na+ and water excretion
246
What happens if aldosterone is given to normal subjects on an adequate Na+ diet?
Na+ retention and K+ loss, weight gain from water retention
247
What occurs as a result of water retention and volume expansion?
ANP release from atrial cells --> loss of Na+ and water i.e Natriuresis
248
What is "aldosterone escape"?
ANP overrides aldosterone effects of Na+ reabsorption
249
Similarly, to Conn's syndrome, patients with water retention and volume expansion, what happens to the K+ levels?
Depleted (hypokalaemia)
250
How does ANP work?
1. Less vasopressin
2. Increased GFR
3. Decreased renin
4. Less aldosterone
5. Decreased BP
251
How does a hyperglycaemic coma occur?
High plasma Glc exceeds Tm so stays in proximal tubule --> exerts osmotic effect to retain water in tubule --> Na+ reabsorption decreases in proximal tubule --> decreases reabsorption of glucose since it shares a symport with Na+ --> decreased movement of water out descending limb of loop of Henle --> less concentrated in ascending limb --> interstitial gradient lost --> ADH mechanism ineffective
252
What happens to renin in hyperglycaemic coma?
Suppressed by juxtaglomerular cells in distal tubule so Na+ reabsorption in distal tubule will be decreased
253
Discuss the osmotic diuresis of uncontrolled DM.
Decrease reabsorption in proximal tubule, in loop of Henle, in distal tubule.
Therefore, wrecks interstitial gradient and decreased ability of ADH to remove water
254
Describe the urine produced by osmotic diuresis in uncontrolled DM.
6-8L of isotonic urine/day
255
In uncontrolled DM, why is there hypotension and and risk of coma?
Large volume of nearly isotonic urine excreted i.e severe salt and water depletion (decrease PV and inadequate BF to the brain.
256
What is the difference between the cause of hypoglycaemia and hyperglycaemia comas?
Hypoglycaemia = inadequate glucose
Hyperglycaemia = hypovolaemia causing little brain perfusion
257
What can loop diuretics cause in relation to K+?
K+ ion wasting
258
What proteins are filtered across the glomerular membrane?
Proteins smaller than albumin
259
Where does filtration occur histologically?
Between podocyte foot processes
260
What is a mesangium cell?
Tree-like group of cells supporting capillaries
261
What are the three types of cells at the glomerulus?
Podocytes
Endothelial cells
Mesangium cells
262
What is the normal pH of arterialised blood?
7.4
263
What ions contribute to pH?
Free H+ ions
264
What are sources of H+?
Respiratory Acid
| Metabolic Acid
265
When do respiratory acids occur?
Carbonic acid is produced form carbon dioxide and water.
266
What happens when there is an increase in respiratory acids?
Increased ventilation
267
When is respiratory acid a problem?
Impaired lung function
268
Where do metabolic acids come from?
- Inorganic: Sulphur containing AAs
| - Organic: FAs, lactic acid
269
What is a major source of alkali?
Oxidation of organic anions such as citrate
270
What is the function of buffers?
Minimize pH changes
271
What is the definition of the Henderson-Hasslebalch equation?
Defines pH in terms of ratio of [A-]/[HA]
272
What is the Henderson-Hasslebalch equation?
pH = pK + log([A-]/[HA])
273
What is the main buffer system?
Bicarbonate buffer
274
What does the quantity of H2CO3 depend on?
The amount of CO2 dissolved in plasma, depends on solubility of CO2 and Pco2
275
In normal arterialised blood pH of 7.4 what is the ratio of bicarbonate and carbonic acid?
20x more bicarbonate than carbonic acid (20:1)
276
What is the "Standard bicarbonate"?
24mmoles/l (22-26 range)
277
What is the normal Pco2?
40mmHg, 5.3kPa (36-44)
278
What is the normal pH of arterialised blood?
7.4 (range = 7.37-7.43)
279
in simple terms, what does the henderson-hasslebach equation show?
pH is proportional to ratio of bicarbonate/PCO2
280
What happens when there is an increase in ECF H+?
Drives reaction to right and increased CO2 is exhaled (increased ventilation)
281
Have H+ ions been eliminated when reaction shifted to right?
No, HCO3- has buffered the H+ and respiratory compensation greatly increased buffering capacity.
Free H+ prevented from contributing to pH
282
What happens if there is a decrease in H+?
Reaction shifted to left
Reduced ventilation
Increased CO2
283
What controls bicarbonate?
The kidney
284
What regulates HCO3?
Kidneys
285
What regulates PCO2?
Respiratory system
286
What other buffer systems are present in the ECF?
Plasma proteins
| Dibasic phosphate
287
What are intracellular buffers?
Proteins
Organic and inorganic phosphates
Erythrocytes
Haemoglobin
288
What results from buffering H+ ions by ICF buffers?
Changes in plasma electrolytes
289
In acidosis, the movement of K+ out of cells causes what?
Hyperkalaemia --> depolarisation of excitable tissues --> VF and death
290
What does bone carbonate provide?
Additional store of buffer in chronic acid loads as in chronic renal failure
291
What does increases in H+ in acidosis leads to with regards to potassium?
Hyperkalaemia
292
Why does hyperkalaemia result from acidosis?
Need to maintain electrochemical neutrality
293
How much acid is buffered in plasma and ICF?
Plasma = 43%
| Cells =57%
294
What is an important buffer in 97% of respiratory acids within cells?
Haemoglobin
295
How does the kidney regulate [HCO3-]?
1. Reabsorbing filtered HCO3-
| 2. Generating new HCO3-
296
How is bicarbonate reabsorbed?
Secrete protons into tubule cells
- > coupled to passive Na+ reabsorption
- > filtered bicarbonate reacts with secreted H+ to form H2CO3
- > Carbonic anhydrase on luminal surface converts to CO2 and H2O
- > CO2 is freely permeable and enters cell
- > in cell CO2 to H2CO3 with carbonic anhydrase
- > dissociates to form H+ and HCO3-
- > HCO3- into peritubular capillaries with Na+
297
Why is HCO3- converted to CO2 to be reabsorbed?
Save the buffer
298
What happens if the normal amount of bicarbonate is not reabsorbed?
Renal failure
299
Are protons excreted/
No
300
What is the minimum urine pH?
4.5-5
301
What is the maximum pH for urine?
8
302
What is the net production of H+/day?
50-100mmoles
303
What is free H+ in urine buffered by?
Dibasic phosphate, (also uric acid and creatinine)
304
What is "titratable acidity"?
Buffering free H+ in urine. Generates new HCO3- and excretes H+
305
When is titratable acidity used?
Acid loads
306
Dibasic phosphate secreted H+ in exchange of what?
Reabsorption of Na+
307
What is the function of the monophonic phosphate?
Removes H+ from the body
308
Why is titratable acidity important?
Generates new HCO3- and excretes H+
309
What is titratable acidity dependent on?
PCO2 of the blood
310
Where does titratable acidity occur?
Distal tubule
311
What is the main source of ammonia?
Deamination of glutamine by renal glutaminase within renal tubules
312
What is the mechanism of ammonium excretion in the distal tubule?
Generation of new HCO3- and net excretion of H+
313
What is the mechanism of ammonium excretion in the proximal tubule?
Generation of new HCO3- and net excretion of H+. Use NH4+/NA+ exchanger
314
What are the limitations of ammonia excretion?
Renal glutaminase activity pH dependent
315
When intracellular pH falls, what happens to renal glutaminase?
Increases --> more NH4+ produced and excreted
316
What is the main response to chronic acidosis?
Augments NH4+ (takes 4-5 days to reach maximal effect)
317
How long does it take for NH4+ PRODUCTION IN KIDNEYS?
4-5 days
318
With regards to pH, what happens in acidosis?
Decreased pH
319
What is respiratory acidosis?
Fall in pH
Related to increase in PCO2
Reduced ventilation
CO2 retention
320
What causes acute respiratory acidosis?
Drugs depressing medullary centres
| Obstruction of airways
321
What causes chronic respiratory acidosis?
Lung disease e.g bronchitis, emphysema, asthma
322
What is the response to chronic respiratory acidosis?
Increase [HCO3-] to protect pH
323
What happens as a result of increased PCO2?
Increase secretion of H+ and HCO3-
| More NH3 produced (since renal glutaminase stimulated)
324
In chronic respiratory acidosis what occurs?
Renal compensation to increase HCO3- BUT can't only normal ventilation can remove disturbance
325
What causes respiratory alkalosis?
Fall in PCO2 (increased ventilation and CO2 blow off)
326
What are acute causes of respiratory alkalosis?
Voluntary hyperventilation
Aspirin
First ascent to altitude
327
What are chronic causes of respiratory alkalosis?
Long term residence to altitude
328
What does a decrease in PO2 to <8kPa stimulate?
Peripheral chemoreceptors --> increase ventilation
329
What causes metabolic acidosis?
Decreased HCO3-
| PCO2 decreased to protect pH
330
What are causes of metabolic acidosis?
- Increase H+ production
- Failure to excrete normal dietary load of H+ as in renal failure
- Loss of HCO3-
331
What is Kussmaul breathing
Degree of hyperventilation in metabolic acidosis --> Breathing very deeply
332
What is Kussmaul breathing a sign of?
Metabolic acidosis: Renal failure, DKA
333
Name 4 causes of metabolic alkalosis.
1. Vomiting
2. Aldosterone excess, excess liquorice
3. Excess HCO3- in impaired renal function
4. Massive blood transfusion
334
How is renal function assessed?
Measure GFR
335
What clinical situations is measuring GFR useful?
1. Renal disease (progression of underlying disease)
| 2. Drugs e.g digitalis and Abx removed via excretion by filtration
336
What is total GFR a sign of?
Sum of all filtration by functioning nephrons
337
If GFR falls, what happens to the [drug] in the plasma?
Increases -> toxicity
338
If low GFR what should you do in relation to some drugs?
Adjust dose appropriate to decreased renal function
339
How is GFR measured?
Plasma clearance tests
340
What is the gold standard plasma clearance tests?
Inulin clearance, polyfructose, loading IV dose of inulin
341
Why is inulin clearance useful to work out volume of plasma filtered through glomerulus i.e GFR?
100% will be filtered and 0% reabsorbed or secreted
342
What is the normal GFR?
125ml/min (women approx 10% lower)
343
What happens to GFR each year after age 30?
Approx 1ml/min/year lost
344
In clinical practice, what is used instead of inulin?
51Cr-EDTA (radioactive substance)
345
In clinical practice, what is routinely used to estimate GFR?
Creatinine clearance
346
What is estimated GFR?
Formulae using serum creatinine which takes into account confounding variables
347
What factors affect serum creatinine?
```
Muscle mass (athletes will produce more)
Dietary intake
Drugs
```
348
What is the normal GFR?
Approx. 100mls/min/1.73m2
349
What is the clearance of glucose?
0
| 100% reabsorbed, 0% excreted
350
What is the clearance of urea?
Less than the of inulin as some urea is reabsorbed
351
What is used to measure renal plasma flow?
Para-amino-hippuric acid (PAH) clearance
352
What is the normal renal plasma flow?
Approx. 660mls/min
353
What is the clearance of penicillin in relation to inulin?
Greater (filtered & excreted, not reabsorbed)
354
How does urine flow from kidneys to ureter?
Peristaltic contraction
355
What prevents reflux of urine?
Oblique angle of ureter entering bladder (vesicoureteric)
356
What is the shape of the pressure-volume curve of the bladder?
Long flat segment (initial entry of urine into bladder) ---> sharp rise (micturition reflex)
357
What controls micturition?
Motor innervation:
PNS (pelvic nerves)
Sparse sympathetic (hypogastric nerve)
358
What is the function of PNS pelvic nerves on micturition?
Increase contraction of detrusor muscle -> increase pressure within bladder
359
What is the function of sparse SNS supply in relation to micturition?
1. Inhibit bladder contraction -> close internal urethral sphincter
2. prevent reflux of semen into bladder during ejaculation
360
What happens if the hypogastric nerve is cut?
Increased micturition frequency
361
What is the sensory innervation of a full bladder?
Stretch receptors activated when bladder fills -> discharge in afferent nerves -> excite PNS flow,
Inhibition SNS flow, inhibit somatic motoneurons to external sphincter -> sensation of fullness
362
What volume of urine in the bladder is required to initiate the spinal reflex?
330-350mls
363
How is urine expelled from urethrea in male vs female?
Male: contractions of bulbocavernous muscle
Female: gravity
364
Name 3 abnormalities of micturition.
1. Interuption of afferent nerves
2. Interuption of afferent and efferent nerves
3. Interuption of facilitatory and inhibitory descending pathways from the brain
365
What do some paraplegic patients train themselves to do?
Initiate voiding by pinching or stroking their thighs (mild mass reflex)
366
What is acidosis caused be?
Decreased HCO3- OR increased PCO2
367
What is alkalosis caused by?
Increased HCO3- OR decreased PCO2
368
For an increase in PCO2 how does the effect on pH differ in chronic and cute respiratory acidosis?
Smaller decrease in chronic than acute
369
In relation to potassium, what can severe acidosis cause?
Hyperkalaemia (VF risk)
370
What treatment should be given for metabolic acidosis?
- Insulin (stimulates K+ uptake)
- Calcium resonium (exchanges Ca2+ for k+)
- IV Ca gluconate
371
Does hypovolaemia or metabolic alkalosis take precedence?
Hypovolaemia
372
If a patient presents with hypovoalemia and metabolic alkalosis, what treatment would you give?
Give NaCl (restore volume then alkalosis will be corrected)
373
What does excess ingestion of liquorice (glycyrrhizic acid) cause?
Metabolic alkalosis
374
What is the normal anion gap?
14-18mmoles/L
375
What is the anion gap?
The difference between the sum of the principle cations (Na+ and K+) and the principle anions (Cl- and HCO3-)
376
In diabetic acidosis, what happens to the anion gap?
Increases
377
A patient presents with the following blood gases values, which acid/base disturbance does he have?
pH = 7.32
[HCO3-] = 15
PCO2 = 30
Metabolic Acidosis
378
A patient presents with the following blood gases values, which acid/base disturbance does he have?
pH = 7.32
[HCO3-] = 33
PCO2 = 60
Chronic respiratory alkalosis
379
A patient presents with the following blood gases values, which acid/base disturbance does he have?
pH = 7.45
[HCO3-] = 42
PCO2 = 50
Metabolic alkalosis
380
A patient presents with the following blood gases values, which acid/base disturbance does he have?
pH = 7.45
[HCO3-] = 21
PCO2 = 30
Acute respiratory alkalosis
381
A patient presents with the following blood gases values, which could be causing his disturbance?
pH = 7.31
[HCO3-] = 36
PCO2 = 7.7
Chronic bronchitis
382
A patient presents with the following blood gases values, which could be causing his disturbance?
pH = 7.25
[HCO3-] = 12
PCO2 = 3.3
Impaired renal function
383
What would happen to GFR if there is efferent arteriole constriction?
GFR would increase
384
How would drinking a large amount of water affect osmolarity and volume of ECF?
Decreased osmolarity and increased volume
385
Where in the kidney does ADH insert aquaporins?
Distal tubule
386
What is released in response to cellular dehydration?
ADH
387
If drug A's clearance is greater than inulin clearance what can be said about the secretion/absorption?
Net secretion
388
If there is ADH deficiency, describe the urine?
More micturation
389
Name a drug that can increase creatinine clearance?
Cimetidine
390
A patient with lung cancer develops the syndrome of inappropriate ADH secretion. What Na+ concentration would you expect to see?
Low (e.g 128mmol/L)
391
Why would you expect to see hyponeutraemia in inappropriate ADH secretion?
Water retention --> hemodilution --> decreased Na+
392
Discuss osmolarity and Na+ levels in pseudohyponatraemia?
Osmolarity normal and very low plasma [Na+]
393
What is pseudohyponatraemia?
Hypertriglyceridaemia
394
Where does spironolactone act?
Inhibits Na+ reabsorption in distal tubule
395
What is the normal level of sodium?
135-145
