Urinary Flashcards
1
Q
What are the 3 important characteristics of substances that can be used to measure GFR?
A
Must be freely filtered across the glomerulus
Must not be secreted, reabsorbed, or metabolised by the cells of the nephron
Must pass directly into the urine
2
Q
What percentage of th embodies total blood flow goes to the kidney?
A
20-25%
~1200ml/min
3
Q
At what spinal level are the kidneys?
A
T11/T12
4
Q
What is the trigone?
A
The shape adapted by the empty bladder due to the 2 uretas and 1 urethra
5
Q
What are the 4 major functions of the kidney (in order of importance)
A
- To maintain a stable internal environment to enable function in all parts of the body (controls conc of ions and small organic molecules)
- Excretion of waste products
- Endocrine (synthesis of renin, erythropoietin, prostaglandins)
- Metabolism (active form of Vit D, catabolism of insulin, PTH calcitonin)
6
Q
Define osmolarity
A
Number of osmosis of solute per litre mmol/l
7
Q
Define osmolality
A
Solute per kilogram of solvent milli-osmole
8
Q
Do machines measure osmolarity or osmolality?
A
Osmolality (milli-osmole)
9
Q
Relative to to ICF, what is the concentrations of Na+ and K+ in the ECF?
A
High Na+, low K+
10
Q
What must kidneys do? (4 things)
A
Control volume
Control osmolarity
Help control pH
Excrete waste products
11
Q
What is the functional unit of the kidney?
A
The nephron (1.5 million of them in each kidney!)
12
Q
What percentages of components have been reabsorbed from the tubule by the end of the PCT?
A
~60-70% of Na+ and H2O
~80-90% of K+
~90% of bicarbonate
~100% of glucose and amino acids
13
Q
How do reabsorbed materials leave the PCT?
A
Via the peritubular capillaries
14
Q
What is the major function of the loop of henle?
A
Creating a gradient of increasing osmolarity in the medulla by counter current multiplication, allowing formation of concentrated urine (more conc. than plasma)
15
Q
What is the distal convoluted tubule the major site for?
A
Site of variable reabsorption of electrolytes and H2O.
The fluid leaving the loop of henle is hypotonic, the DCT removes yet more Na+ and Cl-, and actively secretes H+. H2O may or may not follow electrolytes (if not large volume of urine)
16
Q
How does the distal convoluted tubule function as the major site of variable reabsorption?
A
The fluid leaving the loop of henle is hypotonic, the DCT removes yet more Na+ and Cl-, and actively secretes H+. H2O may or may not follow electrolytes (if not large volume of urine)
17
Q
What controls the Na+ recovery system/DCT/ECF volume
A
Renin angiotensin hormone system
18
Q
What controls the recovery of water in the kidney/distal nephron?
A
ADH hormone system. Controls the permeability of DCT and collecting duct to H2O, controlling ECF osmolarity
19
Q
What is in the cortex of the kidney?
A
Renal corpuscles
20
Q
What is in the medulla of the kidney?
A
Tubules
21
Q
What is in the terminal end of the renal artery/vein of the kidney?
A
Glomeruli, vasa recta
22
Q
What is the renal corpuscle?
A
Glomerulus + bowmans capsule
23
Q
What does the renal corpuscle do?
A
Produces the ultrafiltrate
24
Q
Where are podocytes found, and what do they do?
A
Line the glomerulus, surrounding capillaries like a mesh, allowing filtration sites (spaces between podocyte processes)
25
What type of cells are in the proximal convoluted tubule?
Simple cuboidal epithelium with pronounced brush border
26
What are the 4 parts of the loop of henle?
1. Pars recta
2. Thin descending limb
3. Thin ascending limb
4. Thick ascending limb
27
What type of cells are in the thin descending limb of the loop of henle?
Simple squamous
| No active transport occurring (looks like a capillary with no RBC)
28
What type of cells are in the thin ascending limb of the loop of henle?
Simple squamous
| No active transport occurring (looks like a capillary with no RBC)
29
What type of cells are in the thick ascending limb of the loop of henle?
Simple cuboidal
| Active transport occurs
30
What type of cells are in the distal convoluted tubule?
Simple cuboidal
| Like PCT, but larger lumen and no brush border
31
What is the juxtaglomerular apparatus comprised of?
Macula densa of DCT
Juxtaglomerular cells (of afferent arteriole of glomerulus)
Extraglomerular mesangial cells (AKA lacis cells)
32
How does the collecting duct look hisiologically?
Continuation of DCT (simple cuboidal epithelium), similar to thick loop of henle, but lumen is larger and more irregular (rather than circular)
33
What is the renal pyramid?
A series of progressively larger ducts formed by merging collecting ducts. Empties at renal papilla.
34
What does the ureta look like histiologically?
Muscular tube with 2 layers of smooth muscle (and a 3rd layer in the lower third).
Lined by transitional epithelium
35
What other names might transitional epithelium go by?
Urinary epithelium
| Urothelium
36
What does the bladder look like histiologically?
3 layers of muscle, outer adventitia, transitional epithelium.
37
What are the 4 types of epithelium in the male urethra?
Pre-prostatic
Prostatic
Membranous
Spongy
38
What is the passage of a RBC through the kidney?
Renal artery, One of the 5 segmental arteries, Interlobal arteries, Arcuate arteries, Cortical radiate artery , Afferent arteriole, Glomerulus, Efferent arteriole, Peritubular capillaries, Cortical radiate vein, Arcuate vein, Interlobal vein, Renal vein
39
Is the diameter of the afferent or efferent arteriole wider?
Afferent (creates hydronic pressure)
40
What are the 2 types of kidney nephrons?
Cortical
| Juxtamedullary
41
Describe a cortical nephron
Superficial glomeruli, short loop of henle, next to outer cortex, high concentration of renin. Constitutes 80% of nephrons
42
Describe a juxtamedullary kidney nephron
Glomeruli very close to medullary border. Long loop of henle. Produces concentrated urine. Minimal renin conc. constitutes 20% of nephrons
43
What rate is the average glomerular filtration rate?
90-120mL/min/1.71m2
44
How much plasma delivered to the glomerulus is filtered out?
~20%
| ~1% leaves the body
45
What are the 3 main components to the filtration barrier?
```
Capillary endothelium (permeable)
Basement membrane (acellular gelatinous layer of collagen/glycoproteins. Permeable to small proteins. Glycoproteins are negatively charged and repel Protein movement)
Podocyte layer (pseudopodia interdigitate, forms filtration slits)
```
46
Which molecules filter better through the glomerulus, positive or negatively charged ones?
Positive
47
What is the largest molecule that can diffuse through the glomerulus?
Insulin (5200molecular weight)
48
What are the 3 forces involved in the filtering if plasma?
1. Hydrostatic pressure in capillary
2. Hydrostatic pressure in bowmans capsule
3. Oncotic pressure difference between capillary and tubular lumen
49
What is the main mechanism of autoregulation of the kidney?
Via changing diameter of afferent/efferent arterioles to control pressures and filtration rate in the glomerulus
50
What happens to the afferent arteriole when blood pressure increases?
Constriction (GFR is kept constant)
51
What happens to the afferent arteriole when when blood pressure decreases?
Dilation (GFR is kept constant)
52
What are the limits of BP where the kidney can compensate for to keep GFR constant?
80-180 mmHg
53
What is tubular glomerular feedback?
Changes in tubular flow rate as a result of changes in GFR changes the amount of NaCl that reaches the distal tubule.
54
What would the tubular glomerular feedback response to increased blood pressure be?
Increased Na+ and Cl- retention
55
What do MD cells in DCT respond to? What does this contribute to?
Changes in NaCl arriving in the DCT.
| Contributes to regulation of arterial tone and therefore filtration rate
56
What can the juxtaglomerular apparatus release to reduce GFR?
Adenosine (vasodilator of efferent arteriole)
57
What can the juxtaglomerular apparatus release to increase GFR?
Prostaglandins (vasodilator of afferent arteriole)
58
What happens if NaCl increases?
GFR needs to decrease
Adenosine released (vasodilator of efferent arteriole)
This reduces pressure gradient across glomerulus and therefore slows GFR
59
What happens if NaCl decreases?
```
GFR needs to increase
Prostaglandins released (vasodilator of afferent arteriole)
```
60
What is the relationship between GFR and distal salt concentration limited to?
Acute changes
| Long standing primary disturbances in body fluid volume not regulated like this
61
Where does the majority of reabsorption take place?
PCT
62
On which membrane is the 3Na2KATPase located?
Basolateral
63
How does Na+ move across the apical membrane in the PCT?
Down a concentration gradient
64
How does water move into the PCT?
Down the osmotic gradient
65
What Na+ transporters are present in the PCT?
NaH antiporter
| Na-glucose symporter
66
What Na+ transporters are present in the Loop of Henle?
Na-K-2Cl symporter
67
What Na+ transporters are present in the early DT?
NaCl symporter
68
What Na+ transporters are present in the late DT/CD
ENaC (epithelial Na+ channels)
69
What does SGlut transport?
2Na+ and 1 glucose
| Against the glucose gradient,
70
On which membrane is SGlut found?
Basolateral membrane
71
What has normally been reabsorbed by the end of the PCT?
```
100% filtered nutrients
80-90% filtered HCO3-
67% filtered Na+
65% filtered H2O
65% filtered Cl-
65% filtered K+
```
72
Where does the majority of drug metabolism take place?
Liver
73
Where does the majority of drug excretion occur?
Kidney
74
What does xenobiotic mean?
Foreign
75
What is clearance of a drug?
It's rate of elimination by liver and kidney
76
What does half life describe?
The rate a drug is removed from the body
77
What is clearance rate proportional to?
The drugs free concentration in plasma
78
How does lipophilicity effect drug clearance?
The more lipophilic a drug is, the more easily it can diffuse back out of the lumen into the plasma
79
How does hydrophilicity effect drug clearance?
(Residual electrical charge)
| The more charged a drug molecule is, the less easily it moves back out of the lumen.
80
How does the degree of binding to plasma protein effect drug clearance?
If lots, reduces the amount available for glomerular extraction
81
How does the degree of binding to tissue protein effect the clearance of a drug?
Effectively removes drug from the plasma, thus decreasing amount available for renal clearance
82
What is Vd?
The apparent volume of distribution
83
How is Vd calculated?
By measuring real plasma concentration of a drug (it's impractical to measure drug concentration in all compartments of the body, so it's generalised into a single number)
84
What's it mean about a drug if Vd is high?
Lipohilic, leaves plasma
| Reduces amount of drug available in plasma for excretion by kidney
85
What's it mean about a drug if Vd is low?
Highly charged, confined to plasma
| Increases amount of drug available in plasma for excretion by kidney.
86
What are xenbiotics?
Things the body sees as 'foreign' e.g. Drugs
87
What do the phase 1 and phase 2 enzyme systems work to achieve on xenobiotics?
Increase their ionic charge, therefore reducing lipophilicity, thus making it more difficult for the metabolised drug molecule to diffuse back out of tubular lumen and back into plasma
88
Why is reducing lipophilicity of xerobiotics beneficial?
Makes it more difficult for the metabolised drug molecule to diffuse back out of tubular lumen and back into plasma, thus increasing its secretion
89
What effect does acidic urine have on weak acidic anions?
Weak acidic anions more likely to be protonated - making them electrically neutral and therefore more lipophilic
90
What effect does alkaline urine have on weak acidic anions?
Weak acidic anions not protonated - more excreted.
91
What effect does alkaline urine have on weak bases?
Weak bases more likely to lose a proton, making them electrically neutral and more lipophilic (thus easier to cross nephron)
92
What effect does acidic urine have on weak bases?
Weak bases not deprotonated - more excreted
93
What effect will heart disease (or reduced renal vascular supply) have on the GFR?
Reduce GFR, and thus will reduce clearance
94
What effect does hepatic disease have on renal clearance?
Reduced drug metabolism, so reduced renal clearance
Reduced production of plasma proteins, so increases clearance of drugs bound to this (providing renal function is normal)
95
Define renal clearance
Volume of plasma required to 'totally' remove a given solute per unit time
96
What do you need to know before you are able to calculate renal clearance?
Conc. of physiological marker in plasma and urine
97
Give examples of good physiological markers
Inulin
| Creatinine
98
What must physiological markers be in order to be of use?
Must not be synthesised, degraded or stored in the kidney
99
What are the 2 compartments in the body in which water is found? What separates them?
Intracellular fluid ICF
Extracellular fluid ECF
Separated by a cell membrane
100
Approximately how much water is in a 70kg male?
42 litres
101
Approximately how much water is ICF and ECF in a 70kg male?
28l ICF
| 14l ECF
102
What is the major osmotically active effective solute in the ECF?
Na+
103
What does concentration of Na+ in blood effect?
Effective circulatory volume
| And therefore blood pressure
104
Other than via the kidneys, how else is Na+ lost from the body?
Sweat, Faeces
| Although generally only small amounts
105
What do changes in osmotic pressure and hydrostatic pressure in peritubular capillaries alter?
Proximal tubule Na+ reabsorption (and hence water reabsorption)
106
What stimulates proximal tubule Na+ reabsorption?
RAAS
107
What are the targets within the kidney nephron for the hormone aldosterone?
Principle cells of DCT and CD
108
How does the kidney nephron counteract an increase in renal artery BP?
Reduced number of Na-H antiporter
Reduced Na-K ATPase activity in proximal tubule
Reduced Na+ reabsorption in proximal tubule
Reduced water reabsorption in proximal tubule
This causes increased Na+ excretion and therefore increased H2O excretion - pressure diuresis
Decreases ECF volume
109
What effect does increased blood pressure have on the kidney nephron?
Increases peritubular capillary pressure
Increased renal interstitial pressure
Decreased fluid absorption
Independent of vasomotor activity
110
What effect does high ECF volume have on the renal nephron?
Increased renal artery pressure, large pressure natriuresis and diuresis
111
What effect does low ECF volume have on the kidney nephron?
Decrease in renal artery pressure, small pressure naturesis and diuresis
112
What drives Na+ reabsorption in the kidney nephron?
3Na+ - 2K+ - ATPase on basolateral membrane
113
What is reabsorbed along with Na+?
Cl-
114
Is Cl- absorption active or passive?
Both
115
What is Cl- reabsorption dependent on?
Na+ reabsorption - maintains electro-neutrality
116
What apical Na+ transporter is in the PCT of the kidney nephron?
Na-H antiporter
Na-Glucose symporter
Na-AA cotransporter
Na-Pi
117
What apical Na+ transporter is in the loop of Henle of the kidney nephron?
NaKCC symporter
118
What apical Na+ transporter is in the early DT of the kidney nephron?
NaCl symporter
119
What apical Na+ transporter is in the late DT and CD of the kidney nephron?
ENaC
| Epithelial Na+ channel
120
What are the different possible types of apical Na+ transporter?
```
Na H exchange
Co-transport with glucose
Co-transport with AA or carboxylic acids
CO-transport with phosphate
Aquaporin
```
121
What is the driving forever for reabsorption in the PCT?
Hydrostatic forces in interstitium
Oncotic forces in peritubular capillary (increased due to loss of 20% filtrate at glomerulus, but cells and Protein left in blood)
122
What are the mechanisms for glomerulotubular autoregulation?
Myogenic action - vasculature reacts to changes in BP
| Tubulo-glomerular feedback - 2nd line of defence, alters Na+ excretion
123
What is the equation used to calculate filtered load?
Filtered load = GFR x Concentration
124
What occurs primarily in the descending limb of the loop of henle?
Water reabsorption
| This concentrates Na+ and Cl- ready for active transport in the ascending limb
125
What primarily occurs in the thin ascending limb of the loop of henle?
Na+ reabsorption, passively
126
What primarily occurs in the thick ascending limb of the loop of henle?
Na+ reuptake, and therefore Cl- reuptake also
Na+ reuptake via NKCC2 transporter, powered by 3Na+/2K+ ATPase
K+ ions diffuse via ROMK back into lumen to maintain activity of NKCC3 and Cl- ions move into interstitium
127
Which part of the nephron is most sensitive to hypoxia?
Thick ascending limb as it is very energy dependent
128
What can the ascending limb also be known as?
They diluting segment
| Absorbs NaCl but not H2O
129
Is tubule fluid leaving the loop of Henle hyper, hypo, or iso -osmotic?
Hypo
130
What Na+ transporter is present in the early DT and what type of diuretics is it sensitive to?
NCC transporter
| Sensitive to thiazide diuretics
131
What form of diuretics are ENaC transporters sensitive to? Where in the nephron are they found?
Amiloride diuretics
| Late DT and CD
132
Where is the major site for Ca2+ reabsorption in the kidney nephron?
DCT
133
What controls Ca2+ reabsorption in the kidney nephron?
Hormones - PTH, 1,25-dihydroxyvitamin D
134
What happens to cytosolic Ca2+ in DCT cells?
Immediately bound by calbindin to basolateral aspect of DCT cells
Then transported out by NCX (sodium calcium exchanger)
135
What is the collecting duct divided into?
Cortical and medullary regions
136
What are the 2 distinct cell types found in the cortical collecting duct?
Principle cells
| Type B intercalated cells
137
What do principle cells in the CCD do?
Reabsorption of Na+ via ENaC
| Comprise 20% of cells
138
What do type B intercalated cells in the CCD do?
Active reabsorption of Cl-. Secretion of H+ (AIC) or HCO3- (BIC) more in acids and bases
139
What are the 2 types of intercalated cells?
Acid secreting - AIC
| Bicarbonate secreting - BIC
140
Where are intercalated cells found?
In cortical and outer medullary collecting duct
141
What does a principle cell do?
Absorption of Na+ via ENaC on apical membrane (powered by 3Na/2K ATPase
142
How is Cl- absorbed in the CD?
Principle cells reuptake of Na+ produces luminal (-Ve) charge, which is the driving force for Cl- reuptake via paracellular route
143
How is blood pressure regulated short term?
Adjustment of sympathetic and parasympathetic input to the heart to alter CO.
Adjustment of sympathetic input to peripheral resistance vessels to alter TPR.
144
What is the baroreceptor reflex?
Nerve endings in the carotid sinus and aortic arch are sensitive to stretch.
Increased BP causes stretch - activates afferent pathways - medulla - efferent pathways - activators to decrease BP activated
145
What is control of BP long term directed at?
Control of blood Na+ and thus extracellular fluid volume/plasma volume
146
What are the 3 parallel neurohumoral pathways used for long term regulation of BP?
Renin-angiotensin-aldosterone system (RAAS)
Sympathetic nervous system
Antidiuretic hormone (ADH)
Atrial natriuretic peptide (ANP)
147
Where is renin released from?
Granular cells of juxtaglomerular apparatus (JGA)
148
What stimulates renin release?
Reduced NaCl delivery to distal tubule
Reduced perfusion pressure in the kidney (detected by baroreceptors in afferent arteriole)
Sympathetic stimulation to JGA
149
How is angiotensin converted to angiotensin 2?
Angiotensin - angiotensin 1 (catalysed by renin)
| Angiotensin 1 - angiotensin 2 (catalysed by angiotensin converting enzyme ACE)
150
What does Angiotensin 2 stimulate?
```
Vasoconstriction
Na+ reabsorption at kidney
Stimulates aldosterone (from adrenal cortex)
```
151
How many types of angiotensin 2 receptors are there? What are they called?
2
AT 1 and AT2
(Most actions are via AT1)
152
What type of receptor is AT1?
G-protein coupled receptor
153
What is angiotensin 2s action at arterioles?
Vasoconstriction
154
What is angiotensin 2s action at the kidney?
Stimulates Na+ reabsorption
155
What is angiotensin 2s action at the sympathetic NS?
Increased release of NA
156
What is angiotensin 2s action at the adrenal cortex?
Stimulates release of aldosterone
157
What is angiotensin 2s action at the hypothalamus?
Increases thirst sensation (stimulates ADH release)
158
What are the direct actions of angiotensin 2 on the kidney?
Vasoconstriction of afferent and efferent arteriole
| Enhanced Na+ reabsorption at the PCT (stimulates Na-H exchanger NHE3 in apical membrane)
159
Describe the action of aldosterone on the kidney
Acts on principle cells of collecting duct
Stimulates Na+ (and therefore water) reabsorption
Activates apical Na+ channel (ENaC) and apical K+ channel
Also increases basolateral Na+ extrusion via Na/K/ATPase
160
How does ACE further augmentate the vasoconstrictor effects of angiotensin 2?
ACE is also one of the kinase enzymes that breaks down the vasodilator bradykinin
161
What effect does high levels of sympathetic stimulation have on the kidney?
Reduces renal blood flow (Vasoconstriction of arterioles, decreased GFR, decreased Na+ excretion)
Activates apical Na/H exchanger and basolateral Na/K ATPase in PCT.
Stimulates renin release from JGcells, leading to increased angiotensin 2 levels and increased aldosterone levels (increased Na+ reabsorption)
162
What direct effects does sympathetic stimulation of kidney have?
Acts on arterioles to reduce renal blood flow
Stimulates granule cells of afferent arteriole to release renin (via RAAS axis)
Stimulates Na+ reabsorption from PCT
163
What is ADHs main role?
Formation of concentrated urine by returning water to control plasma osmolarity.
Increases H2O reabsorption in distal nephron
164
What stimulates ADH release?
Plasma osmolarity
| Severe hypovolaemia
165
What is ADH also known as?
Arginine Vasopressin.
166
What do atrial natriuretic peptides ANP do?
Promote Na+ excretion
167
Where are atrial natriuretic synthesised/stored?
In atrial myocytes.
| Released from atrial cells in response to stretch (low pressure/volume sensors in atria)
168
What effect does reduced effective circulation volume have on the release of ANP?
Inhibits release of ANP to support BP (reduced filling of heart, less stretch, less ANP released)
169
What are the actions of atrial natriuretic peptide ANP?
Causes vasodilation of the afferent arteriole
Increased blood flow increases GFR
Also inhibits Na+ reabsorption along the nephron
Acts in opposite direction to other neurohumoral regulators (causes natriuresis, loss of Na+ in urine)
If circulating volume is low, ANP release is inhibited, supports BP
170
What do prostaglandins act as?
Vasodilators
171
What effect can locally acting prostaglandins (mainly PGE2) have upon the kidney glomerulus?
Enhance glomerular filtration and reduce Na+ reabsorption
172
When is the vasodilator effects of prostaglandins important in the kidney?
When levels of angiotensin 2 are high; acts as a buffer to excessive vasoconstriction produced by SNS and RAAS. Helps to maintain renal blood flow and GFR in the presence of vasoconstrictors
173
What do NSAIDs do?
Inhibit cyclo-oxygenase (COX) pathway involved in the formation of prostaglandins.
174
When must you be careful of prescribing NSAIDs?
Administration of NSAIDs when renal perfusion is compromised can further decrease GFR - acute kidney failure
175
Where is dopamine used in the kidney formed?
Locally in the kidney from circulating L-DOPA.
176
Where in the kidney are dopamine receptors found?
Present on renal blood vessels and cells of PCT and TAL
177
What does dopamine cause in the kidney?
Vasodilation and increases renal blood flow
| Reduces reabsorption of NaCl; inhibits NH exchanger and Na/K ATPase in principle cells of PCT and TAL
178
What is essential, or primary hypertension?
The cause is unknown (95% of cases)
179
What is secondary hypertension?
The cause can be defined e.g. Renovascular disease, aldosteronism, cushings, chronic renal disease
It's important to treat the primary cause!
180
How may renovascular disease cause secondary hypertension?
Occlusion of renal artery (renal artery stenosis) causing a fall in perfusion pressure of that kidney. Decreased perfusion pressure leads to increased renin production, activation of RAAS. Vasoconstriction and Na+ retention at other kidney.
181
How may renal parenchymal disease cause secondary hypertension?
Earlier stage may be a loss of vasodilator substances. In later stages Na+ and H2O retention due to inadequate glomerular filtration (volume-dependent hypertension)
182
How might Conns syndrome cause secondary hypertension?
Conns syndrome - aldosterone secreting adenoma (hypertension and hypokalaemia)
183
How might Cushing's syndrome cause secondary hypertension?
Excess secretion of glucocorticoid cortisol. At high concentrations, acts on aldosterone receptors, Na+ and H2O retention
184
How might a tumour of the adrenal medulla cause secondary hypertension?
Phaeochromocytoma - secretes catecholamines (noradrenaline and adrenaline)
185
What hypertension drugs target the RAAS?
ACE inhibitors. Prevent the formation of active angiotensin 2
186
What hypertension drugs target vasodilators?
L-type Ca2+ blockers
187
How do L-type Ca2+ channel blockers work to reduce hypertension?
Reduce Ca2+ entry to vascular smooth muscle cells - relaxation.
188
What diuretics are generally used for hypertension?
Thiazide diuretics
| Inhibit Na/Cl CO-transporter on apical membrane of cells in distal tubule
189
Are beta blockers used to treat hypertension?
No
Will reduce effects of sympathetic output (decreasing HR and contractility). Would only be used if other indications such as previous MI
190
What proportion of total body fluids is ECF and ICF ?
1/3 ECF
| 2/3 ICF
191
Where is the majority of the K+ in the body?
ICF (98% - mainly in skeletal muscle cells, liver, RBC, bone)
192
What maintains the difference between ICF and ECF K+ levels?
Na+/K+ ATP ase
193
Why is maintaining ECF K+ conc so low so important?
Due to K+S effect on the resting membrane potential
And therefore it's effects on excitability of cardiac tissue - life threatening arrhythmias with hyperkalaemia/hypokalaemia
194
What effect does low K+ level have on excitability?
Further to reach threshold potential - decreased excitability
195
What effect does high K+ level have on excitability?
Decreased distance to threshold potential - increased excitability
196
How is K+ immediately regulated?
By internal balance - moving K+ between ECF and ICF
197
How is K+ regulated longer term?
External balance - adjusting renal K+ excretion
198
Describe the events that follow K+ consumption
Intestine and colon absorb dietary K+
Blood K+ increases, potentially to dangerous levels
BUT 4/5 K+ moves into cells within minutes
After slight delay, kidneys begin to excrete K
Excretion complete in 6-12hrs
199
What mediates movement of K+ from ECF to cells?
Na+/K+ ATPase
200
What mediates the movement of K+ from cells to ECF?
K+ channels
201
List 3 factors that increase K+ uptake by cells
Hormones (act via Na+/K+ATPase) e.g. Insulin, aldosterone, catecholamines
Increased K+ conc. in ECF
Alkalosis (low ECF H+ conc)
202
List 5 factors that promote K+ shift out of cells
```
Exercise
Cell lysis
Increased in ECF osmolality
Low ECF K+ conc
Acidosis (increased ECF H+ conc)
```
203
What does K+ in splanchnic blood stimulate?
Insulin secretion by pancreas
204
What effect does insulin have on K+ uptake by cells?
Increases, as increases activity of Na/K ATPase
205
How would you treat hyperkalaemia?
IV insulin and dextrose
206
What effect does K+ in blood have on aldosterone secretion?
Stimulates secretion
207
How does aldosterone stimulate K+ uptake?
Stimulates Na/K ATPase
208
How do catecholamines stimulate K+ uptake?
Act via beta2 adrenoreceptors, which stimulate Na/K ATPase and thus cellular uptake of K+
209
What is produced during high intensity exercise and trauma to offset high ECF K+ rise?
Increased catecholamines
| Offset K+ rise by increasing K+ uptake by other cells
210
Describe how K+ is released during exercise
Net release of K+ during recovery phase of action potential, K+ leaves cell
Skeletal muscle damaged during exercise, releases K+
Increase in plasma K+ proportional to intensity of exercise
211
What prevents dangerously high ECF K+ levels during exercise?
K+ uptake by non-contracting tissues
212
Describe the effects of acidosis on potassium balance in a cell
Acidosis
H+ shift into cells
Reciprocal K+ shift out of cells
213
Describe the effects of alkalosis on the K+ balance of cells
Shift of H+ out of cells
| Reciprocal K+ shift into cells
214
Does acidosis lead to hyper or hypo kalaemia?
Hyperkalaemia
215
Does alkalosis lead to hyper or hypo kalaemia?
Hypokalaemia
216
Describe the movement of K+ and H+ ions in hyperkalaemia
Hyperkalaemia, shift of K+ into cells
Reciprocal shift of H+ out of cells
Hyperkalaemia leads to acidosis
217
Describe the movement of K+ and H+ ions in hypokalaemia
Hypokalaemia, shift of K+ out of cells
Reciprocal shift of H+ into cells
Hypokalaemia leads to alkalosis
218
Where is K+ excretion monitored?
Late DT and cortical collecting ducts of kidney nephron
219
Describe what happens to K+ in the kidney
K+ freely filtered at glomerulus
K+ reabsorbed at proximal tubule (67%), thick ascending loop of henle (20%), distal tubule, cortical collecting duct (via intercalated cells), medullary collecting duct
K+ secreted at distal tubule & cortical collecting duct (principle cells)
220
Describe how K+ secretion occurs in principal cells in the distal tubule
Na/K ATPase activity in basolateral membrane increases intracellular K+, and decreases intracellular Na+
Na+ moves from lumen into cell down its conc. gradient (via apical ENaC), creating an electrical gradient
This together with high intracellular K+ creates a favourable electrochemical gradient for K+ secretion via apical K+ channels
221
What effect does aldosterone have on K+ secretion by principal cells of kidney?
Increases K+ secretion
| Increases transcription of relevant proteins (increases Na/K ATPase, increases K+ channels, increases ENaC)
222
What effect does ECFs K+ concentration have on K+ secretion by principal cells of kidney?
Directly stimulates Na/K ATPase and increases permeability of apical K+ channels
Also stimulates aldosterone secretion
223
What effect does acidosis have on K+ secretion by principal cells of kidney?
Acidosis decreases K+ secretion (inhibits Na/K ATPase, decreases K+ channel permeability)
224
What effect does alkalosis have on K+ secretion by principal cells of kidney?
Increases K+ secretion
| Stimulates Na/K ATPase, increases K+ channel permeability
225
What effect does increased distal tubular flow rate have upon K+ secretion?
Washes away luminal K+, increasing K+ loss
226
What effect does increased Na+ delivery to distal tubule have on K+ secretion?
More Na+ absorbed by principal cells, resulting in more K+ loss
227
How is K+ absorbed by intercalated cells?
Actively, via H+/K+ ATPase in apical membrane
228
Where are intercalated cells in the kidney?
Distal tubule
| Cortical collecting duct
229
What can changes in ECF K+ concentration effect?
Alter cell membrane resting potential
Alter neuromuscular excitability
Resulting in arrhythmias, CA, muscle paralysis
230
What might cause hyperkalaemia?
```
Increased K+ intake (unlikely unless inappropriate use of IV K+)
Decreased renal excretion (kidney injury, low aldosterone state, drugs blocking K+ excretion - ACE inhibitors, K+ sparing diuretics)
Internal shifts (diabetic ketoacidosis, cell lysis, metabolic acidosis)
```
231
What are the clinical features of hyperkalaemia?
Heart - altered excitability, arrhythmias, heart block
GI - neuromuscular dysfunction - paralytic ileus
Acidosis
232
What is the emergency treatment for hyperkalaemia?
IV calcium gluconate (reduce K+ effect on heart)
IV Glucose and insulin (shift K+ back into ICF)
Nebuliser beta agonists (salbutamol)
Remove excess K+ (dialysis)
233
What is the long term treatment for hyperkalaemia?
Treat cause
Reduce K+ intake
Measures to remove excess K+ (dialysis in acute or chronic kidney injury).
Oral K+ binding resins to bind K+ in gut
234
What may cause hypokalaemia?
Problems of external balance - excessive loss GI, diarrhoea, vomiting). Renal loss of K+ (diuretic drugs, osmotic diuresis, high aldosterone levels)
Problems of internal balance (shifts of K+ into ICF e.g. Metabolic alkalosis)
235
What are the clinical features of hypokalaemia?
Heart - altered excitability, arrhythmias
GI - neuromuscular dysfunction, paralytic ileus
Skeletal muscle - neuromuscular dysfunction, muscle weakness
Renal - unresponsive to ADH
236
What effect does hypokalaemia have on heart muscle excitability?
Hypopolarised RMP - more fast Na+ channels available in active form, heart more excitable
237
What is the treatment for hypokalaemia?
```
Treat cause
Potassium replacement (IV/oral).
If due to increased mineralocorticoid activity (high aldosterone levels), K+ sparing diuretics, which block action of aldosterone on principal cells.
```
238
What are the ECG features of hyperkalaemia?
High T wave, depressed ST segment, prolonged PR interval, P wave absent (atrial standstill), intraventricular block, ventricular failure
239
What are the ECG features of hypokalaemia?
Low T wave, high U wave, low ST segments
240
What cells do K+ absorption at the collecting duct?
Alpha-intercalated cells
241
How is K+ absorbed in the kidney medulla?
Luminal and transcellular absorption
242
How is K+ absorbed in the PCT?
Paracellularly (solvent drag early, lumen - positive potential late)
243
How is K+ absorbed in the TAL?
Transcellular and paracellular (NKCC2, lumen positive potential K+ and Cl-)
244
Why does K+ absorption require such fast balancing?
Amount of K+ absorbed in the GI after a meal is approximately equal to the amount of K+ present in the ECF
245
What effect does adding HCO3- have on K+ absorption into the ICF?
Aids K+ to ICF absorption
246
What pH should the blood be at?
pH 7.35-7.45
247
What concentration of H+ ions should be in the blood?
44.5-35.5 nmol/l
248
What effect does alkalaemia have on Ca2+ ions? What are the consequences of this?
Lowers free Ca2+, causing Ca2+ ions to come out of solution. This increases neuronal excitability, can lead to paraethesia and tetany
249
What can Ca2+ ions coming out of solution lead to?
Increased neuronal excitability, can lead to paraethesia and tetany
250
How does acidaemia effect electrical excitability?
Increases plasma K+ conc
251
What effect may increased H+ conc have on proteins? What can this effect?
Denatures/disturbs them. Can effect muscle contractility, glycosis, hepatic function
252
At what pH is acidosis life threatening?
Below pH 7.0
253
How is plasma pH determined?
Ratio of the concentrations of HCO3-/pCO2 (via hendleson-hasselbalch equation)
Should be maintained at a 20:1 ratio CO2:O2
254
What ratio should CO2:O2 be in the blood?
20:1
255
What effect can hypoventilation have on plasma pH
Hypoventilation - hypercapnia - fall in plasma pH
| Respiratory acidaemia
256
What effect can hyperventilation have on plasma pH?
Hyperventilation - hypocapnia - plasma pH rise
| Respiratory alkalosis
257
What controls pCO2?
```
Central chemoreceptors (change respiratory rate for disturbances in pCO2). Slower response, but account for ~80% of effect.
Peripheral chemoreceptors detect changes in pCO2 and pH of plasma. Respond rapidly but have overall smaller effect.
```
258
What can compensate for changes in pCO2?
Changes in HCO3-
| Ratio = pH
259
What controls the concentration of HCO3- in the blood?
Kidneys (despite RBCs producing it)
260
What happens, with regard to HCO3-, to acid produced by tissues?
Reacts to form CO2, which is blown off at the lungs. This leads to a fall in HCO3-, therefore a decrease in pH
This can be compensated for by increasing ventilation.
261
What chemoreceptors detect a change in plasma pH?
Peripheral
262
When might plasma HCO3- levels rise?
E.g. After much vomiting
263
How might increases in plasma HCO3- be compensated for?
Decreasing ventilation
264
How can the kidney correct disturbances in pH?
Varying excretion of HCO3- (very easy to lose it)
| Making more HCO3-
265
How do kidneys produce more HCO3-?
Have a very high metabolic rate, so produce lots of CO2, which then reacts with H2O, producing HCO3- (which enters plasma) and H+ (which is excreted in urine)
Kidney can also make HCO3- from amino acids (producing NH4+, which enters urine)
266
Where is 80% of HCO3- reabsorbed in the kidney nephron?
In the PCT
267
What drives HCO3- reabsorption in the PCT?
Na+ gradient (established by NaK ATPase)
268
Describe HCO3- recovery in the PCT
Na+ movement down gradient (established by NaK ATPase) drives H+ movement out of cells via NHE-3
H+ in lumen reacts with HCO3- to form CO2 (carbonic anhydrase is present on apical membrane and inside tubular cells)
CO2 moves into the cell and reacts with H2O to form more HCO3-, which moves across basolateral membrane to ECF (Na3HCO3- cotransporter)
269
Describe the creation of HCO3- in the proximal tubule. What happens to the products?
Glutamine is converted to alpha-ketoglutarate, producing HCO3- and ammonium NH4+
HCO3- enters ECF
NH4+ enters lumen
270
Describe the creation of HCO3- in the distal tubule
Metabolic activity produces CO2, so H+ ions need to be secreted and buffer to keep producing HCO3- (Na+ gradient not enough to drive secretion of H+), via H+ATPase.
H+ buffered by filtered HPO4+ and excreted NH4+
271
What is the lowest pH of urine?
pH 4.5
272
How is the lowest possible pH of urine (4.5) achieved?
No HCO3- is secreted (all has been recovered)
| Some H+ buffered by phosphate, some has reacted with ammonia to form NH4+
273
Approximately how much H+ is secreted per day?
50-100mmol
| Needed to keep the concentration of HCO3- normal
274
What controls H+ secretion?
Kidneys
275
What happens if ECF concentration of HCO3- is low?
More HCO3- moves out of cells to ECF, more H+ in cells
276
What is the kidney cellular response to acidosis?
Decreased pH enhances the activity of Na+/H+ exchanger
Decreased pH enhances ammonium production in proximal tube
Decreased pH enhances activity of H+ ATPase (proton pump) in distal tube
Increased capacity to export HCO3- from tubular cells to ECF
277
What is the anion gap?
Associated ion with metabolic acids (e.g. Lactic, keto...) left after H+ reacts with HCO3- to produce CO2 (exhaled).
Anion replaces HCO3-
278
How is the anion gap calculated?
The difference between the concentrations of
(Na+ + K+) - (Cl- + HCO3-)
Main cations - main anions
279
What is a normal value for the anion gap?
10-15mmol/l
280
What does an increased anion gap indicate?
HCO3- has been replaced by an anion other than Cl-
281
Do all metabolic acidosis create an anion gap?
Nope
282
What does a fall in pH stimulate in the kidney?
Acid secretion
| HCO3- recovery
283
What does a rise in the pH of tubular cells lead to?
A fall in H+ excretion and reduction in HCO3- recovery
284
When is HCO3- excretion compromised?
If there is also volume depletion
Capacity to lose HCO3- is reduced because of high rate of Na+ recovery
Recovering Na+ favours H+ excretion and HCO3- recovery
285
What effect does hyperkalaemia have on HCO3-?
```
K+ moves out of cells
H+ moves into cells
Favours H+ excretion
HCO3- recovery
More K+ reabsorption in distal nephron
```
286
What effect does hypokalaemia have on HCO3-?
K+ moves into cells
H+ moves out of cells
Favours HCO3- excretion (H+ recovery)
Less K+ reabsorbed in nephron
287
What value are most body fluids osmotically, so that they are isotonic to cells?
280-310mOsm/kg
288
Through what range can urine osmolarity go through?
50-1200 mOsm/kg
289
What approximate value is urine osmolarity in a normal hydrated person?
500-700mOsm/kg
290
What do disorders of water balance manifest as?
Changes in body fluid osmolarity
291
What detects changes in plasma osmolarity?
Hypothalamic osmoreceptors
292
What are the 2 efferent pathways to effect plasma osmolarity?
ADH and thirst
| Effects kidney and brain (behavioural), water excretion and water intake
293
Where are osmoreceptors in the brain located?
Organum vasculosum of the lamina terminalis (OVLT), which is anterior and ventral to the third ventricle
294
What feature of the organum vasculosum of the lamina terminalis (OVLT) aids its ability to detect plasma osmotic changes?
Fenestrated leaky endothelium, exposed directly to systemic circulation (on plasma side of blood brain barrier) - in direct contact with plasma
295
What does the organum vasculosum of the lamina terminalis (OVLT) do?
Senses changes in plasma osmolarity, signals secondary responses - concentration of urine or thirst
296
Under what conditions is ADH released?
Predominant water loss
297
Where is ADH secreted from?
Posterior pituitary gland
298
What controls ADH secretion?
Negative feedback loops
299
Should ADH conc. ever reach zero?
Nope
300
What is more important, blood osmolarity or volume?
Volume!
When faced with circulatory collapse, kidneys continue to conserve H2O even if this will reduce osmolarity of body fluids
301
What is the analogue of thirst?
Salt ingestion
302
Where is ADH produced?
Produced by neurosecretary cells in the hypothalamus
303
What sort of peptide is ADH?
Small, 9 AA long
304
What are some other names for ADH?
Vasopressin, argipressin, arginine vasopressin AVP
305
What effect does ADH have on the kidney?
Increases permeability of collecting duct to water and urea
306
What is diabetes insipidus?
When plasma ADH levels are too low
307
What might cause diabetes insipidus?
Damaged hypothalamus or pituitary glands e.g. Brain injury (base of skull fracture), tumour, aneurism ect
308
What is nephrogenic diabetes insipidus?
Kidney insensitivity to ADH (acquired)
309
What effect does diabetes insipidus have on the kidney?
Water is inadequately reabsorbed from the collecting ducts, so a large quantity of urine is produced
310
How can you manage diabetes insipidus?
ADH injections
| ADH nasal spray
311
What is SIADH?
Syndrome of inappropriate ADH secretion
312
What characterises SIADH?
Excessive release of ADH from PP gland or another source. Dilutional hyponatriemia, in which the plasma sodium levels are lowered and total body fluid is increased.
313
What aquaporin channels are present in the proximal tubule?
AQP1
| AQP7
314
What aquaporin channels are present in the thin descending limb?
AQP1
315
What aquaporin channels are present in the ascending limb?
None
316
What aquaporin channels are present in the collecting duct?
AQP2
AQP3
AQP4
Mostly in medullary portion
317
What happens in the kidney if there is little ADH present?
No aquaporin in basolateral membrane of latter DCT and collecting ducts
Therefore limited water reuptake in latter DCT/collecting ducts
Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content
Loss of a large amount of hyposmotic urine - diuresis
318
What happens in the kidney if ADH is present?
ADH causes insertion of aquaporin channels to basolateral membrane, enabling water to move out of collecting duct into hyperosmotic environment
319
How is a counter current established in the kidney?
Juxtamedullary nephron - long loop of henle establishes gradient vertically, vasa recta helps maintain this osmotic gradient
320
What effect does the thick ascending limb have on establishing the medullary gradient?
Removes solute without water, therefore increasing osmolarity of the interstitium
321
Describe the action of loop diuretics
Block NaK2Cl transporters, medullary interstitium becomes isotonic and copious amounts of dilute urine is produced
322
Describe the action of the descending limb with regards to osmolarity
Highly permeable to water (due to AQP1 channels), which are always open. Not permeable to Na+, so Na+ remains in descending limb and its concentration increases
323
What is the maximum osmolarity at the tip of the loop of henle?
1200mOsm/kg
324
Describe the action of the ascending limb with regards to osmolarity
Actively transports NaCl out of tubular lumen into interstitial fluid. Impermeable to water. Osmolarity decreases. Fluid entering DCT has a low osmolarity of 100mOsm/kg; it is hyposmotic
325
What is counter current multiplication?
Active transport of Na+ out of ascending limb increases its concentration in the interstitial fluid surrounding the loop of henle. This is enabled by the vasa recta
326
What enables counter current multiplication?
The vasa recta
327
At what level is the osmolarity at the corticomedullary border?
Isotonic (~300mOsm/kg)
328
What level of osmolarity is the medullary interstitium?
Hyperosmotic (up to 1200mOsm/kg at papilla)
329
What aids osmotic gradient in the kidney?
Urea (not usually an effective osmole)
330
What determines whether a substance is an effective osmolarity?
If a membrane enables certain solute to cross freely, then it is totally ineffective at exerting an osmotic force across the membrane
331
Is urea hydrophilic or hydrophobic?
Hydrophilic
332
Where is urea reabsorbed?
Medullary collecting duct
| Cortical collecting duct cells are impermeable to urea
333
What effect does ADH have on urea in the kidney?
Fractional excretion of urea decrease, and urea recycling increases
334
What maintains the concentration gradient produced by the loop of henle?
The vasa recta, acts as a counter current exchanger
335
What is bloodflow in renal medulla like?
Low (5-10% total RPF)
| Needs to deliver nutrients and maintain medullary hyper-tonicity
336
Has the vasa recta got any capacity for active transport?
Nope
337
Describe osmotic stratification in medullary interstitium if ADH is present
Counter current multiplier give NaCl gradient
| Also cortex to papilla gradient of urea
338
Describe what happens in the descending limb of the vasa recta
Isoosmotic blood enters hyperosmotic mileu of medulla (high concentration of Na+ ions, Cl- ions, and urea)
Ions and urea diffuse into lumen of vasa recta
Osmolarity of blood in vasa recta increases as it reaches tip of loop
339
Describe what happens in the ascending limb of the vasa recta
Blood ascending has higher concentration of solute than surrounding interstitium
Water moves in from the descending limb of the loop of henle
340
Define 'diuretic'
A drug/substance that promotes diuresis
| Usually by increasing renal excretion of water and sodium, therefore causing a reduction of ECF volume
341
When might diuretics be useful, in general?
Conditions where Na+ and H2O retention cause expansion of ECF volume e.g. HF, cirrhosis, nephrotic syndrome
342
What are the stages in the formation of urine?
1 - Filtration
2 - Selective reabsorption of most of the solutes and water
3 - Secretion of substances
343
How do diuretic generally work?
Blocking reabsorption of Na+ and H2O by the tubule fraction excretion (FE)
344
What channel is common to all segments of the tubule?
Na+/K+ ATPase
345
What channels are on the apical membrane of the proximal CT?
NaH Antiporter
Na-Glucose symporter
Na-AA symporter
346
What channels are on the apical membrane of the loop of henle?
Na-K-2Cl symporter
347
What channels are on the apical membrane of the early DT?
NaCl symporter
348
What channels are on the apical membrane of the late DT and CD
ENaC
| Epithelial Na+ Channels
349
Describe tubular reabsorption of Na+ by principle cells of late DT and CD
Na-K-ATPase in basolateral membrane pumps out Na+
Na+ enters cells via ENaC on apical membrane
Na+ reabsorption favours K+ secretion by creating a luminal negative potential (secreted via K+ channels)
350
What effect does aldosterone have on the expression of Na+ channels?
Increases expression of NaK ATPase, ENaC and K+ channels.
351
What effects do diuretics blocking ENaC have on K+ secretion?
Diuretics blocking ENaC also reduces K+ secretion
352
What are common sites of action of diuretics?
Loop of henle - loop diuretics
Distal convoluted tubule - thiazide diuretics
Collecting duct - potassium sparing diuretics
Aldosterone antagonists
353
Give some examples of loop diuretics
Furosemide
| Bumetanide
354
Give some examples of thiazide diuretics
Metalozone
Indapamide
Bendroflumethiazide
355
Give an examples of potassium sparing diuretics
Amiloride, trimterene
| Aldosterone antagonists
356
Give an example of an aldosterone antagonist
Spirolactone
357
Describe the classification of diuretics
Loop diuretics - inhibitors of Na-K-2Cl symport
Thiazide diuretics - inhibitors of NaCl symport
K+ sparing diuretics - inhibitors of renal Na+ channels/aldosterone antagonists
Inhibitors of carbonic anhydrase
Osmotic diuretics
358
Give an example of a diuretic that works via inhibiting carbonic anhydrase
Acetazolamide
359
Give an example of an osmotic diuretic
Mannitol
360
What are the 4 mechanisms via which diuretics may work?
- By direct action on cells to block Na+ transporters in the luminal membrane (drug secreted into lumen in PCT, acts from within lumen on transporters)
- By antagonising the action of aldosterone
- By modification of filtrate content, osmotic diuretics (small molecules freely filtered at glomerulus, but not reabsorbed. Increase osmolarity of filtrate, reducing H2O and Na+ reabsorption throughout tubule)
- By inhibiting activity of enzyme carbonic anhydrase in the PCT (interferes with Na and HCO3- reabsorption in PCT)
361
Upon what transporters do diuretics acting on the loop of henle work on?
NaK2Cl transporter
362
What proportion of filtered Na+ is absorbed in the loop of henle?
25%
363
What helps drive absorption of Ca2+ and Mg2+?
K+ that has been carried across apical membrane drifts back via K+ channels, creating luminal positive gradient...
364
Describe the action of loop diuretics
Secreted into lumen in the PCT and travel downstream to act on the loop of henle
Very potent diuretics (20-30% of filtered Na+ reabsorbed in the loop) - segments beyond have limited capacity to reabsorbed the resulting flood of Na+ and H2O
365
How do loop diuretics get into the tubular lumen?
Secreted into lumen in the PCT via organic anion pathway
366
When might you use loop diuretics?
Heart failure (diuretic effect = vaso/venodilation, decreases pre/afterload on heart)
Acute pulmonary oedema (furoseminide IV for rapid access)
Fluid retention and oedema in nephrotic syndrome, renal failure, cirrhosis of liver
Hypercalcaemia (impairs Ca2+ reabsorption, increasing urinary excretion of Ca2+)
367
What sort of diuretics act on the early distal tubule?
Thiazides
368
What channel do thiazide diuretics block?
NaCl transporter
369
What effect can thiazide diuretics have on Ca2+ reabsorption?
Increased Ca2+ reabsorption
370
Describe how thiazide diuretics work
Secreted into lumen in PCT, travel downstream to act at DCT
Block NaCl transporter in DCT
Increase Na+ (and H2O) loss in urine
Reduces Ca2+ loss in urine (increases Ca2+ reabsorption)
371
How do thiazide diuretics get into the tubular lumen?
Secreted into lumen at PCT
372
What potency do thiazide diuretics have?
Less than loop diuretics!
Only 5% Na+ reabsorption inhibited
Therefore ineffective in renal failure
373
How much Na+ reabsorption is inhibited by thiazide diuretics?
~5%
374
What are thiazide diuretics primarily used to treat?
Hypertension
375
What diuretics act on the late DT and CD?
Inhibitors of epithelial Na+ channels
| Aldosterone antagonists
376
What are some features of diuretics acting on the late DT and CD?
Mild diuretics affecting only 2% of Na+ reabsorption
Reduce Na+ channel activity (directly or indirectly)
Reduce loss of K+
Risk of hyperkalaemia
377
What is a risk of diuretics acting on the late DT and CD?
Can produce life-threatening hyperkalaemia, especially if used alongside ACE inhibitors, K+ supplements or in patients with renal impairment
378
When would you use spironolactone? (An aldosterone antagonist)
Treatment of hypertension due to primary hyperaldosteronism (com's syndrome - adrenal hypertension)
Treatment of ascites and oedema in cirrhosis
In addition to loop diuretics to in heart failure
As additional therapy in hypertension not controlled by ACE inhibitors ect
379
What are ENaC blockers?
Mild diuretics with a K+ sparing effect
380
When are ENaC blockers used?
In combination with K+ losing diuretics to minimise K+ loss
381
Where is carbonic anhydrase found in the kidney?
Within the brush border of PCT cell
382
What is a risk of using carbonic anhydrase inhibitors?
Can cause metabolic acidosis due to loss of HCO3- in urine
383
When might you use osmotic diuretics?
Useful for cerebral oedema (IV)
384
What are some possible consequences of using osmotic diuretics?
Can cause loss of H2O, Na+ and K+ in the urine
385
How is K+ secreted in the DT and CD?
Passive process
Driven by electric-chemical gradient. Rate of K+ secretion depends on the concentration gradient across apical membrane, and the rate of Na+ absorption - inward movement of Na+ ions creates a favourable lumen negative gradient for K+ secretion
386
What does the rate of K+ secretion in the DT and CD depend on?
Rate of K+ secretion depends on the concentration gradient across apical membrane, and the rate of Na+ absorption - inward movement of Na+ ions creates a favourable lumen negative gradient for K+ secretion
387
List some things other than diuretic use which may contribute to hypokalaemia
```
Excess diuresis reduces ECF volume
Activation of RAAS
Increased aldosterone secretion
Increased Na+ absorption and K+ secretion
Hypokalaemia
```
388
What effect do loop diuretics have on K+ excretion?
Increase Na+ absorption by principal cells, favourable electrical gradient for K+ excretion
(Also loop and thiazide diuretics - both increase Na+ and H2O delivery to late DT and CD)
389
Describe effect of thiazide diuretics on K+ secretion
Faster flow rate of filtrate in tubule lumen, K+ secreted into lumen is washed away faster, lower K+ concentration in lumen. Favourable chemical gradient for K+ secretions
390
What is particularly at risk of happening when K+ sparing diuretics are used?
Hyperkalaemia
| Na+ reabsorption reduced, less K+ lost in urine
391
What is it important to measure when using diuretic therapy?
Electrolyte Na/K levels
392
When are diuretics used?
Conditions with ECF expansion and oedema
393
How does congestive heart failure cause peripheral oedema?
Increases systemic venal pressure
394
How does reduced renal perfusion lead to expansion of the ECF?
Activation of RAAS, Na+ and H2O retention
395
What is nephrotic syndrome?
Glomerular disease - increase in GBM permeability to protein. Proteins are filtered and lost in urine, causes low plasma albumin, results in low plasma oncotic pressure - peripheral oedema.
Reduced circulatory volume - RAAS activated - expansion of ECF - more oedema
396
Where is splanchnic circulation?
GI
397
Is ascites transudate or exudate?
Transudate
398
What might cause bladder stones?
- Bladder outflow obstruction - urethral stricture, neuropathic bladder (doesn't contract normally), prostate obstruction
- Presence of foreign body - catheter, non-absorbable sutures
- Some are passed down from upper urinary tract
399
What are the consequences of bladder stones?
Can cause urine outflow obstruction. Anuria/painful bladder distension
400
What are some other names for renal stones?
Kidney stone, renal calculus, nephrolith
401
When do renal stones generally present?
30+yrs
| 2:1 male:female
402
What can renal stones be made of?
```
Calcium stones:
Calcium oxalate - usually with calcium phosphate (apatite)
Calcium phosphate alone
Uric acid
Struvite 'infection stones', urease stones, triple phosphate stones (magnesium ammonium phosphate hexahydrate, from infection by bacteria that have urease)
Other types (rarer)
Cysteine stones
Drug stones
Ammonium acid rate stones
```
403
What causes struvite 'infection stones' (urease stones, triple phosphate stones)
Magnesium ammonium phosphate hexahydrate, from infection by bacteria that have urease
404
When are renal stones comprised of calcium phosphate alone seen?
Frequently in hyperparathyroidism and renal tubular disease
405
When might cysteine stones occur?
Rare genetic disorder cystinuria
406
Give some examples of kidney stones that occur as a result of drugs
Indinavir (treatment for HIV)
Triamterene (diuretic)
Sulphadiazine (sulphonamide antibiotic)
407
Why do urinary stones form?
If there is urine supersaturation with minerals - solvent contains more solute than it can hold in solution. Seed crystals form by nucleation - 1st step is formation of a new structure by self assembly. A physical, not chemical reaction.
408
In what circumstances might urinary stones form?
Decrease in water content - dehydration
Increase in mineral content - hypercalcaemia and hypercalciuria, hyperoxaluria, hyperuricaemia, hyperuricosuria, cysteinuria
Decrease in solubility of solute in urine - some solute more soluble at high pH and some at low pH
409
What stones does acid urine favour the formation of?
Calcium oxalate and uric acid stones
410
What stones does alkaline urine favour the formation of?
Calcium phosphate stones
411
What renal tubular acidosis result in?
Persistently alkaline urine and decreased urinary citrate excretion
412
What happens to calcium phosphate in alkali?
Precipitates
413
What happens to calcium phosphate in acid?
Dissolves
414
What happens if you put a bone in vinegar (ethanoic acid)?
Goes rubbery - calcium phosphate has dissolved away
415
What is a likely cause of uric acid and cysteine stones?
Supersaturation
416
How do calcium oxalate stones form?
75% grow like stalactites attached to exposed interstitial deposits of calcium phosphate 'Randall's plaque' on the tips of renal papillae (composed of a core of calcium phosphate surrounded by calcium oxalate)
Otherwise, can form on plugs protruding from ducts of bellini or free in solution
417
List some causative factors for urinary stones
Urine status - low urine flow, obstruction, infection
Genetic/congenital factors - primary metabolic disturbances e.g. Cystinuria, kidney abnormalities e.g. Polycystic kidneys, medullary sponge kidneys
Drugs
418
Describe the presentation of calcium oxalate stones
5% associated with hypercalcaemia and hypercalciuria - treatable!
55% have hypercalciuria without hypercalcaemia - can be associated with hyperabsorption of calcium from the gut or impairment in renal tubular absorption of calcium
5% association with hyperoxaluria - hereditary or secondary to intestinal over absorption in patients with enteric disease
419
What might cause calcium oxalate stones due to hypercalciuria and hypercalcaemia?
Hyperparathyroidism, diffuse bone disease, sarcoidosis
420
Proportionally, how much Ca2+ is locked away in bone?
Over 99%
ECF conc 1000-10000 times lower than ICF
Cell membranes pump out Ca2+
421
What regulates Ca2+ conc in the ECF?
PTH
Calcitriol
1,25 dihydroxy vitamin D
Calcitonin
Have effect in gut, kidney and bone
422
Where are Ca2+ sensing receptors located in the body?
Parathyroid glands, kidney, brain and other organs
423
How does PTH increase serum calcium?
Increases osteoclastic resorption of bone (rapid)
Increases intestinal absorption of Ca2+ (slow)
Increases synthesis of 1,25-(OH)2D3
Increases renal tubular resorption of Ca2+
Increases excretion of phosphate
424
How does vitamin D effect Ca2+ levels?
Increases Ca2+ absorption in the gut
| Increases calcification and resorption in bone
425
Where is calcitonin produced?
Thyroid C cells
426
How does calcitonin decrease serum Ca2+?
Inhibits osteoclastic bone resorption
| Increases renal excretion of calcium and phosphate
427
What is the most common metabolic abnormality in Ca2+ stone formation?
Hypercalciuria
428
What might cause hypercalciuria?
Hypercalcaemia
Excessive dietary intake of Ca2+
Excessive resorption of Ca2+ from skeleton (prolonged immobilisation, weightlessness)
Idiopathic (increased absorption of Ca2+ from the GIT)
429
What can be given to astronauts to help prevent them getting hypercalciuria due to resorption of unused skeletal bones?
Potassium citrate
430
What are the possible causes of hypercalcaemia?
```
Hypersecretion of PTH, resulting in increased bone resorption
Destruction of bone tissue
Other mechanisms (excessive Vit D ingestion, thiazide diuretics, sarcoidosis, milk-alkali syndrome - excessive Ca2+ intake)
```
431
What is sarcoidosis?
Macrophages activate Vit D precursor
432
What might lead to hypersecretion of PTH?
Primary - parathyroid hyperplasia or functional tumour
Secondary - to renal failure (which causes retention of phosphate and hence hypocalcaemia)
Ectopic - secretion of PTH related protein by malignant tumour (legal squamous cell carcinoma of lung)
433
What might cause destruction of bone tissue (leading to hypercalcaemia)?
Primary tumour of bone marrow (e.g. Myeloma)
Paget's disease of bone (accelerated bone turnover)
Immobilisation (reduces bone formation whilst reabsorption continues
Diffuse skeletal metastases
434
What are the most common causes of hypercalcaemia?
Hyperparathyroidism and malignancies
435
What are the main clinical signs of hypercalcaemia?
Bones, stones and moans.
Painful bones - fractures
Renal stones
Abdominal groans - constipation, peptic ulcers pancreatitis, gallstones
Psychic moans - depression, lethargy, seizures
Severe muscle weakness (opposite of tetany in hypocalcaemia!)
436
What is hyperoxaluria?
Rare autosomal recessive genetic disorder of oxalate synthesis (primary hyperoxaluria types 1 and 2)
Increased intestinal oxalate absorption secondary to GI disease (England chrons disease) usually with an intestinal resection (increased absorption of oxalate from colon)
Dietary habits - high oxalate intake (spinich, rhubarb, tea, nuts)
Low calcium intake (increases GI absorption of oxalate)
437
What type of stones are generally present with UTIs?
Struvite stones (mixed infection stones)
438
What are struvite stones comprised of?
Magnesium ammonium phosphate with variable amounts of calcium
439
What sort of infections usually produce struvite stones? Why?
Infection with organisms with the enzyme urease which hydrolyses urea to ammonium hydroxide (proteus species e.g. Proteus mirabilis)
Also production of mucoprotein from infection provides an organic matrix on which stones can form
440
What are particularly large urinary stones called?
Staghorn calculus
441
When are staghorn calculus predominantly seen?
In people predisposed to UTIs - spinal cord injury, neurogenic bladder, vesicoureteric reflux, obstruction uropathy
442
When are uric acid stones seen?
In hyperuricaemia, and in people with tendency to have urine with pH of less than 5.5
443
What is a key fact about uric acid stones?
They are radiolucent - can't be seen on X-ray
444
What is hyperuricosuria?
High uric acid in urine
445
What is hyperuricaemia?
High uric acid in blood
446
What is the endpoint of purine metabolism?
Uric acid
447
When might hyperuricaemia be seen?
Seen in idiopathic gout
Secondary consequence of increased cell turnover (lympho or myeloproliferative disorders) after chemotherapy (tumour lysis syndrome)
448
How do renal stones present?
Asymptomatic, but can be seen on radiography
Renal colic, dull ache on loins
Recurrent UTIs
Urinary tract obstruction
Haematuria
Renal failure
If urinary tract obstruction and fluid intake is increased, result is an increase in pain
449
How long do renal bouts generally last?
20-60mins
450
What causes bouts of renal colic?
Caused by peristaltic contractions or spasms of the ureter as it attempts to expel stone
451
Where is the pain in renal colic felt?
Radiates from flank to iliac fossa and inner thigh (in distribution of 1st lumbar nerve)
452
What often accompanies the pain felt in renal colic?
Nausea/vomiting, pallor, sweat, restlessness. Haematuria common.
453
What generally happens to untreated renal colic?
Subsides in a few hours
454
What is urolithiasis?
The formation of stony concretions in the bladder or urinary tract
455
What does MSU stand for (with regards to urinary investigations)
Midstream specimen of urine
456
What might you be looking for in a MSU (midstream specimen of urine)
RBCs, urinary casts, urinary crystals, culture, (cause or consequence of stones?)
457
What might you be looking for in a serum test when investigating urinary stones?
Urea, creatinine, electrolytes, calcium levels
458
What investigations might you do in urolithiasis?
```
MSU (midstream sample of urine)
Serum
Plain abdominal x-ray
CT kidney, ureter and bladder
Pass urine through serve to catch calculi for chemical analysis
```
459
Why aren't x-rays the best way to look for calculi?
60% of stones are radiopaque (mostly Ca2+ containing stones). Uric acid stones are radiolucent
460
Why is a CT of the kidney, ureter and bladder good for use in urolithiasis?
Better than USS - almost all stones can be seen. Ideally during pain.
Can see stones and dilated renal pelvis
Can see uric acid stones
Identifies any primary renal disease predisposing to stone formation
461
What size urological stones can usually be passed (90%)?
<5mm diameter
462
What size urological stones usually require intervention to be passed?
>7mm diameter
463
What are some possible complications of uric stones?
Acute pyelonephritis +- gram negative septicaemia
Pressure necrosis of the renal parenchyma
Urinary obstruction and hydronephrosis
Ulceration through the wall of the collecting system
464
What are the possible treatments for renal colic?
Analgesia (IV diclofenac or pethidine), warmth to site of pain, bed rest
Ureteroscopy (usually for stones in lower ureter - like endoscopy...)
Percutaneous nephrolithotomy (surgery)
Extracorporal shock wave lithotripsy ESWL
465
What does ESWL stand for?
Extracorporal shock wave lithotripsy
466
When might you use ESWL (Extracorporal shock wave lithotripsy)?
Most commonly for renal stones near the pelvis
467
How does ESWL (Extracorporal shock wave lithotripsy) work?
Lithrotriptor delivers external, focused, high intensity probes of ultrasonic energy. Takes 30-60 mins. Fragments stones, so they can then be passed spontaneously.
468
How can you prevent getting urinary stones?
Keep hydrated!
Decrease excretion of Ca2+ or oxalate (thiazide diuretics)
Potassium citrate alkalinise urine - reduces risk of calcium oxalate, uric acid and cysteine stones. Also forms soluble complexes with Ca2+. Can induce phosphate stones
469
What effect doe thiazide diuretics have on Ca2+ conc. in the urine?
Decreases such
470
What percentage of women will have had at least 1 UTI by the age of 24?
~30%
471
What are UTIs a common source of?
Gram negative septicaemia
472
In whom do most UTIs occur?
Females (shorter urethra)
Obstruction - enlarged prostate, pregnancy, stones, tumours
Neurological problems - incomplete emptying, residual volume
Ureteric reflex - ascending infection from bladder especially in children
473
What might cause a urinary tract obstruction at the PUJ?
Calculi
474
What might cause a urinary tract obstruction at the ureta?
Calculi, Ca2+, retroperitoneal fibrosis
475
What might cause a urinary tract obstruction at the bladder?
Neuropathic bladder
476
What might cause a urinary tract obstruction at the VUJ?
Calculi
477
What might cause a urinary tract obstruction at the bladder neck?
Hypertrophy
478
What might cause a urinary tract obstruction at the prostate?
BPH/Ca2+
479
What might cause a urinary tract obstruction at the urethra
Stricture
480
What adaptations enables bacteria to colonise the urinary tract?
Fimbriae allow attachment to host epithelium. K antigen permits production of polysaccharide capsule. Haemolysins damage host membranes and cause renal damage. Urease breaks down urea creating a favourable environment for bacterial growth.
481
What is cystitis?
Frequency and dysuria (lower UTI)
482
What is acute pyelonephritis?
Upper UTI
483
What is chronic pyelonephritis?
Renal inflammation and fibrosis due to recurrent and persistent renal infection, vesicoureteral reflux, or other cause of urinary tract obstruction
484
When might asymptomatic bacteriuria become a problem?
If patient then becomes pregnant
485
What are some clinical signs and symptoms of lower UTI?
Dysuria, frequency, urgency, sometimes low grade fever
486
What are some clinical signs and symptoms of upper UTI (pyelonephritis)?
Fever, loin pain, may have dysuria/frequency
487
What is an uncomplicated UTI?
'An infection by a usual organism in a patient with a normal urinary tract and normal urinary function'
488
What is a complicated UTI?
UTI when one or more factors present that predispose the person to persistent infection, recurrent infection, or treatment failure.
489
Give some examples of when an UTI could be classed as 'complicated'
```
Abnormal urinary tract (e.g. Vesicoureteric reflux, indwelling catheter ect.)
Virulent organism (e.g. Staph aureus)
Impaired host defences (e.g. Poorly controlled diabetes, immunosuppression)
Impaired renal function
```
490
IN PRACTISE, what is classed as an 'uncomplicated' infection?
Healthy, non-pregnant, woman of child bearing age.
| All others are treated as 'complicated' (so culture urine)
491
What is the clinical consequence of a UTI being classed as uncomplicated?
No need to culture urine
492
How might you obtain a specimen collection for a UTI?
```
MSU - cleansing not required in women
Clean catch in children - no antiseptic
Collection bag (20% false positives)
Catheter sample
Supra-pubic aspiration
Transportation (4 degrees C, +- boric acid)
```
493
What does dipstick testing analyse?
Leucocyte esterase
Nitrile
Haematuria
Proteinuria
494
How is the turbidity of urine relevant to infection?
If urine is clear, infection is unlikely
495
What is dipstick testing useful for?
Useful to exclude UTI in children >3yrs, men with mild/non-specific symptoms, elderly/institutionalised women
496
When is dipstick testing not useful?
Acute uncomplicated UTI in women
Men with typical/severe symptoms
Catheterised patients
Older patients without features of infection (asymptomatic bacteriuria common)
497
Why is culturing urine beneficial?
```
Investigation of children, males, and other 'complicated' infections
Increased sensitivity
Epidemiology of isolates
Susceptibility data
Control of specimen quality
```
498
What would you analyse in a urine culture report?
```
Clinical details again - symptoms, previous antibiotics (might decrease sample size)
Quality of specimen
Delays in culture
Microscopy (if available)
Organisms isolated
```
499
What is urethral syndrome?
```
Low-count bacteriuria
Fastidious organisms
Vaginal infection/inflammation
Sexually transmitted pathogens -urethritis
Mechanical, physical and chemical causes
```
500
When is imagine of the urinary tract particularly useful?
In septic patients to identify renal involvement.
| Considered in all children with UTI
501
What might cause sterile pyuria?
Antibiotics, urethritis (chlamydia/gonococci), vaginal infection/inflammation, chemical inflammation, tuberculosis, appendicitis, fastidious organisms
502
With whom is there a high prevalence of asymptomatic bacteriuria?
High prevalence in older people, particularly elderly females
503
What is often associated with pyuria? What is a consequence of this?
Associated pyuria
| Therefore positive dipstick/culture - so do not routinely dipstick/culture
504
Is asymptomatic bacteriuria associated with increased risk of morbidity/mortality?
Nope
505
When might asymptomatic bacteriuria require treatment?
In pregnancy and urological surgery
506
What is the treatment for UTI?
```
Increase fluid intake
Address underlying disorder
3 day course for uncomplicated UTI
5-7 day course for complicated UTI
CSU - only treat if systemically unwell
```
507
What is the length of course for an uncomplicated UTI?
3 day course for uncomplicated UTI
508
What is the length of course for an complicated UTI?
5-7 day course for complicated UTI
509
What is the treatment for simple cystitis?
Uncomplicated infections can be treated with trimethoprim or nitrofurantoin.
3 day course just as effective as 5 or 7 days, but decreases risk of resistance
510
What is the treatment for complicated lower UTI?
Trimethoprim, nitrofurantoin or cephalexin may be used - review susceptibility report. 5-7 day course. Post treatment follow up cultures in paediatric patients and pregnant women
511
Why is amoxicillin not appropriate treatment for complicated lower UTI?
50% of isolates are resistant
512
What is the treatment for pyelonephritis/septicaemia?
14 day course. Use agent with systemic activity (not nitrofurantoin). Possibly IV initially unless good PO absorption and patient well enough. Co-amoxiclav, ciprofloxacin, gentamicin.
513
How is gentamicin administered?
IV only
514
Is gentamicin nephrotoxic?
Yes
515
When is prophylaxis used for UTI?
If 3 or more episodes in one year with no underlying testable condition
516
What prophylaxis might be used for UTI?
Trimethoprim or nitrofurantoin
| Single nightly dose, ensure all breakthrough infections are documented
517
What nerve roots innervates the detrusor muscles?
S2, 3, 4 (keeps the piss off the floor)
| Pelvic nerves
518
What nerve roots control the urinary sphincter?
Pudendal nerve S2, 3, 4
519
What normally happens as the bladder fills?
Compliance (receptive relaxation). Sensation of bladder filling, nodetrusor contraction
520
What normally happens on voiding of the bladder?
Voluntary initiation, complete emptying
521
What lower neurological problems might occur with bladder emptying?
Low detrusor pressure. Large residual urine +- overflow incontinence. Reduced perional sensation, lax anal tone.
522
What upper neurological issues may occur with bladder emptying?
Constant contractions. High pressure, dilated ureters, thickened detrusor. Urine goes back up to kidneys, can damage them. Poor coordination with sphincter. Detrusor sphincter dyssunergia.
523
List some storage symptoms of lower UTIs
Frequency, urgency, nocturia, incontinence
524
List some voiding symptoms of lower UTIs
Slow stream, splitting/spraying, intermittency, hesitancy, straining, terminal dribble.
525
List some post-micturition symptoms of lower UTIs
Post micturition dribble. Feeling of incomplete emptying
526
What is stress urinary incontinence?
The complaint of involuntary leakage on effort or extortion or sneezing/coughing
527
What is urge urinary incontinence?
The complaint of involuntary leakage of urine accompanied by or immediately proceeded by urgency
528
What is mixed urinary incontinence?
The complaint of involuntary leakage of urine associated with urgency and also exertion, effort, sneezing or coughing
529
What are the types of urinary incontinence?
Stress urinary incontinence
Urge urinary incontinence
Mixed urinary incontinence
Overflow incontinence
530
What is overactive bladder syndrome?
Urgency, frequency, nocturia
| Prevalence is much higher than that of urgency urinary incontinence
531
What are the risk factors for urinary incontinence?
O&G: pregnancy/childbirth, pelvic surgery, pelvic prolapse
Predisposing: race, family predisposition, anatomical abnormalities, neurological abnormalities
Promoting: co-morbidities, obesity, age, UTI, drugs, menopause, increased infra-abdominal pressure, cognitive impairment
532
How is the type of UTI categorised?
History
533
How would one examine a patient with a UTI?
BMI, abdominal examination to exclude palpable bladder. Digital rectal exam - prostate (male), limited neurological exam. Females - external genitalia (stress test - cough). Vaginal exam
534
What investigations would you do for a patient with urinary incontinence?
Mandatory: dipstick (UTI - haematuria, proteinuria, glucosuria)
Consider: basic non-invasive urodynamics, frequency - volume chart, bladder diary (>3days), post-micturition residual volume (in patients with voiding dysfunction)
Optional: invasive urodynamics (pressure - flow studies +-video). Pad tests. Cystoscopy
535
How would you determine how to manage a patient with urinary incontinence?
Depends on symptoms, degree of bother, effects of treatment on other symptoms, previous other treatments.
Should be individualised, systematic approach
536
Describe conservative management of urinary incontinence
Modify fluid intake, weight loss, stop smoking, avoid constipation, decrease caffeine intake, timed voiding (fixed schedule)
537
How might you manage contained incontinence (for patients unsuitable for surgery who have failed conservative or medical management)?
Indwelling catheter (urethral or suprapubic), sheath device (adhesive condom attached to catheter tubing bag), incontinence pads
538
What might pelvic floor muscle training be used for?
Stress urinary incontinence specific management.
| 8 contractions, thrice daily. At least 3 months duration
539
What pharmacological treatments might be used for stress urinary incontinence?
Duloxetine - combined noradrenaline and serotonin uptake inhibitor. Increases activity in the striated sphincter during filling phase. Not recommended by NICE as 1st or 2nd line, but can be offered as an alternative to surgery.
540
What surgical options are there for females with stress urinary incontinence?
```
Permanent intention - low tension vaginal tapes (commonest), open retropubic suspension procedures, classical sling procedures.
Temporary intention (e.g. If further pregnancies are planned) - intramural bulking agents
```
541
What surgical options are there for males with stress urinary incontinence?
Artificial urinary sphincter. Male sling procedure
542
Describe urgency urinary incontinence specific management
Bladder training - schedule of voiding e.g. Every hr, must wait in between. Increase intervals by 15-30mins each week until 2-3hr interval has been reached. At least 6wks duration
543
What pharmacological treatments are available for urge urinary incontinence?
Anticholinergics - acts on muscarinic receptors M2 M3
Oxybutynin
Beta3 adrenoceptor agonist mirabegron. Increases bladder capacity to store urine.
544
What side effects occur with anticholinergics (act on muscarinic receptors)
Due to their effects on other M receptors at other sites
M1 - CNS, salivary glands
M2 - Heart smooth muscle
M3 - Smooth muscle (ocular and intestinal), salivary glands
M4 - CNS
M5 - CNS, eye
545
Describe how botulinum toxin might be used to treat urge urinary incontinence
Potent biological neurotoxin. Inhibits release of ACh at pre-synaptic neuromuscular junction causing targeted flaccid paralysis. Mainly type A used clinically
Duration of action only 3-6months (needs to be redone)
546
Describe how surgery may be used to treat urge urinary incontinence
Sacral nerve neuromodulation (probe inserted which disrupts the nerve signals from spinal cord)
Autoaugmentation, augmentation cytoplasy, urinary diversion (no bladder at all)
547
What are the 'compartments' of the renal system that can go wrong?
Glomerular, tubular, interstitial, vascular
548
What is nephrotic syndrome?
Filter can leak - proteinuria, haematuria. Swelling due to low blood albumin. (O for oedema!)
549
What is nephritic syndrome?
Filter can block 'renal failure'. Reduced renal function, acute kidney failure. Haematuria, hypertensive. Decreased eGFR
550
What is a primary kidney injury?
Just effects the glomerulus
551
What is a secondary kidney injury?
Systemic disease that effects kidneys, e.g. Diabetes
552
What are the sites within the glomerulus where immune complex deposition (antigen-antibody complex/circulating factors) may occur?
Subepithelial (podocytes)
Within GBM
Subendothelial
Mesangial (and paramesangial)
553
What is the likely site of kidney injury in nephrotic syndrome?
Podocytes/subepithelial damage
554
What are they common primary causes of podocytes/subepithelial damage (causing nephrotic syndrome)
Minimal change glomerulonephritis
Focal segmental glomerulonephritis
Membranous glomerulonephritis
555
What are they common secondary causes of podocytes/subepithelial damage (causing nephrotic syndrome)
Diabetes mellitus
| Amyloidoses
556
What is minimal change glomerulonephritis?
Heavy proteinuria or nephrotic syndrome. No foot processes on podocytes (only visible under electron microscope). Unknown cause. No immune complex deposition. Responds to steroids. May reoccur. Usually no progression to renal failure. Incidence increases with increasing age (usually presents in childhood/adolescence). Circulating factor damaging podocytes.
557
What is FSGS spectrum (minimal change glomerulonephritis)?
More common in adults/older patients. Nephrotic. Less responsive to steroids. Glomerulosclerosis (scarring). Circulating factor damaging podocytes. Progressive to renal failure. Collagen deposition in glomerulus
558
Describe membranous glomerulonephritis
```
Immune complex deposits, probably autoimmune. May be secondary (associated with other pathologies e.g. Lymphoma). Immune complexes deposited near podocytes. Complex activation leads to cell injury IgG. Antigen either already on podocytes or gets there separately (complex can't get through BM!). Attracts antibody.
Rule of 1/3s
1/3 Get better
1/3 Stay the same
1/3 Progress to renal failure
```
559
What is the commonest cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
560
How does diabetes effect the kidneys?
Progressive proteinuria. Progressive renal failure. Microvascular. Mesangial sclerosis --> nodules. Basement membrane thickening.
561
Describe IgA Nephropathy
Commonest glomerulonephritis. Classically presents with visible/invisible haematuria. Relationship with mucosal infections. Variable histological features and course. +- proteinuria. Significant proportion progress to renal failure. No effective treatment (only ways to support renal function).
562
Is there a cure for IgA nephropathy?
No effective treatment (only ways to support renal function).
563
Does IgA progress to renal failure?
Significant proportion progress to renal failure.
564
Where is a particularly easy target, in the kidney, for IgA and antigen?
There is no BM/filtering system between the blood and mesangium
565
What might cause hereditary nephropathy?
```
Thin GBM nephropathy
Benign familial nephropathy
Isolated haematuria
Thin GBM
Benign course
Alport syndrome
X-linked
Abnormal collagen 4
Associated with deafness
Abnormal appearing GBM
Progression to renal failure
```
566
What is the glomerular basement membrane primarily comprised of?
Collagen 4
| Hence any abnormalities in collagen 4 will cause issues
567
What can you use to look for hereditary nephropathies?
Electron microscope
568
Describe goodpasture syndrome (anti GBM)
Relatively uncommon, though clinically important. Rapidly progressive GN. Acute onset nephritic syndrome. Classically described associated to pulmonary haemorrhage (smokers). Autoantibody to collagen 4 in BM, but BM is ubiquitous. Treatable by immunosuppression and plasmaphoesis if caught early. Replace patients plasma with donor - rapidly get rid of antibody. Cannot be seen on electron microscopy (just antibody)
569
What causes goodpasture syndrome?
Autoantibody (usually linked to collagen 4) suddenly starts to attack glomerulus
570
What is vasculitis?
A group of systemic disorders. No immune complex/antibody deposition. Associated with anti neutrophil cytoplasmic antibody (ANCA) - activates neutrophils, attack cells e.g. Endothelial cells as line blood vessels, inflammation of blood vessels. Nephritic presentation (RPGN). Treatable if caught early. Urgent biopsy service. Endothelial target.
571
What does 'focal' mean, with regards to kidney disease?
Involving <50% of the glomeruli on light microscopy
| diffuse>50%
572
What does 'diffuse' mean, with regards to kidney disease?
Involving >50% of the glomeruli on light microscopy
| Focal <50%
573
What does 'segmental' mean, with regards to kidney disease?
Involving part of the glomerular tuft
574
What does 'global' mean, with regards to kidney disease?
Involving the entire glomerular tuft
575
What does 'membranous' mean, with regards to kidney disease?
Thickening of the glomerular capillary wall
576
What does 'proliferative' mean, with regards to kidney disease?
Increased number of cells in glomerulus, cells can be either proliferating glomerular cells or infiltrating circulating inflammatory cells
577
What does 'crescent' mean, with regards to kidney disease?
Accumulation of cells (mostly mononuclear cells) within bowman space. Often compress capillary tuft, associated with more severe disease
578
What does 'glomerulosclerosis' mean, with regards to kidney disease?
Segmental or global capillary collapse - presumed there is little filtration across sclerotic area
579
What does 'glomerulonephritis' mean, with regards to kidney disease?
Any condition associated with inflammation in glomerular tuft
580
List some risk factors associated with malignancy of the urinary tract
Increased age, family history, BRCA 2 gene mutation, ethnicity (black>white>Asian)
581
What are the issues for PSA (prostate specific antigen) screening?
Over diagnosis, over treatment, quality of life (comorbidities of established treatments), cost effectiveness, other causes of raised PSA (infection, inflammation, large prostate)
582
What is the clinical presentation of urinary malignancy?
Usually asymptomatic, or urinary symptoms (benign enlargement of prostate/bladder overactivity +- CaP), bone pains. Sometimes haematuria (if advanced CaP)
583
What is the typical diagnostic pathway of a urinary malignancy?
Digital rectal examination, serum PSA (prostate specific antigen), TRUS (transracial ultrasound, guided biopsy of prostate), lower UTI symptoms, transurethral resection of prostate TURP
584
What factors would influence treatment of a urinary malignancy?
Age, DRE (localised, T1/T2), locally advanced (T3), advanced (T4). PSA level. Biopsies (Gleason grade, extent). MRI scan and bone scan (nodal and visceral metastases)
585
If a urinary malignancy is local, what treatment might you use?
Established Rxs. Surveillance. Robotic radical prostatectomy. Radiography. External beam, low dose brachytherapy.
586
What treatment might you use for metastatic CaP? With regards to urinary malignancy
Hormones +- chemotherapy. Surgical/medical castration, LHRH agonists. Palliation single dose radiotherapy. Bisphosphonates (zoledronic acid). Chemotherapy (docetraxel). New treatments?
587
Below what PSA (prostate specific antigen) level is bone metastases highly unlikely ?
<10ng/ml
588
How would bone metastases appear on a bone scan?
Sclerotic (osteoblasts) 'hotspots' on bone scan
589
How might you treat locally advanced CaP (with regards to urinary malignancy)?
Surveillance, hormones, hormones + radiotherapy
590
What are the classifications for haematuria?
Visible
| Non-visible (symptomatic and asymptomatic)
591
What are the different types of cancer for urinary malignancies?
Renal cell carcinoma, upper tract transitional cell carcinoma TCC, bladder cancer, advanced prostate carcinoma
592
What might cause symptoms similar to a urinary malignancy?
Stones, infection, inflammation, benign prostatic hyperplasia (large)
593
What investigations might you do for a urinary malignancy?
Blood - FCB, U&Es
Urine - culture and sensitivity (cytology)
Radiology - ultrasound (tumour, stone, blockage)
Endoscopy - flexible cystoscopy
594
How does bladder cancer Presentation differ from men to women?
Less common in woman, but usually more advanced on presentation
595
What is the most common type of cancer in bladder cancer?
90% transitional cell carcinoma TCC
596
List some risk factors for bladder cancer
Smoking, occupational exposure, schistosomiasis
597
Exposure to what sort of occupational things might increase risk of bladder cancer?
Rubber/plastics manufacture, arylamines, carbon, crude oil, polyaromatic hydrocarbons, painter, mechanic, hairdresser ect....
598
Is chemotherapy alway systemic?
No, e.g. TUR bladder tumour treatment
599
What treatment might be used for bladder cancer?
Low risk non muscle invasive TCC (G1, G2, Ta) - check cystoscopies +- invasive chemotherapy
High risk non muscle invasive TCC (G3, Tis, T1) - check cystoscopies. Intravesical immunotherapy.
Muscle-invasive TCC. Neoadjuvant chemotherapy + radical cystectomy or radiotherapy
600
What sort of carcinoma are most upper urinary tract tumours?
Renal cell carcinoma RCC (95%)
601
What increases a persons risk of getting renal cell carcinoma?
Smoking, obesity, dialysis
602
Where does renal cell carcinoma frequently spread to?
Lymph nodes, IVC to right atrium, perinephric spread
| 30% metastases on presentation
603
What is the treatment for renal cell carcinoma?
Surveillance, radical nephrectomy, partial nephrectomy, developmental ablation.
Palliative - molecular therapies targeting angiogenesis (new 1st choice), poorly responsive to chemo/radiotherapies
604
Are upper urinary tract malignancies common?
No, only ~5%
605
What increases a persons likelihood of getting upper urinary tract malignancies?
Smoking, phenacetin abuse, balking nephropathy
606
What is the standard treatment for upper urinary tract malignancy ?
Nephro-ureterectomy (kidney, far, ureter, cuff of bladder)
607
What sort of cancer is in the upper urinary tract malignancies?
Upper tract transitional cell carcinoma
608
What initial inveatigations would you do for upper urinary tract malignancies?
USS, hydronephrosis, UT urogram, filling defects ureteric structure, retrograde pyelogram, ureteroscopy, biopsy, washings for cytology
609
What are the functions of the kidney?
Excretion - salt and electrolytes, water, acid, other metabolites, waste solutes
Glomerular permselectivity
Tubular functions - urine concentration/dilution, bicarbonate reclamation, NH4 secretion
Hormonal/vitamins - vitamin D, renin, erythropoietin
610
What might the symptoms of a failure of kidney excretion be?
```
Hyperkalaemia
Na+ overload paralleled by H2O overload (oedema, peripheral and pulmonary, hypertension)
Acidosis - acidotic breathing
Lethargy and fatigue
Uraemic syndrome
```
611
How might an error in glomerular permselectivity present?
Proteinuria
| Haematuria
612
How might impaired tubular function present?
Impaired concentrating ability - frequency of urine, altered diurnal urine concentrating ability. Nocturia
Contributes to acidosis
May result in glycosuria with normal blood glucose
613
How might impaired kidney hormonal function present?
Metabolic bone disease
Anaemia
Hypertension
614
How is most kidney disease detected?
Opportunistically through screening at risk populations (hypertension, heart disease, diabetes, UT obstruction, systemic disease)
615
Describe asymptomatic microscopic haematuria
Common, may be due to urinary infection, polycystic kidneys, renal stones, renal/bladder tumours ect....
Increased likelihood of micro haematuria associated with proteinuria and/or hypertension of glomerular disease
Patients over 45yrs require cystoscopy alas first investigation
616
What colour is the urine in episodic macroscopic haematuria usually?
Brown/smokey rather than red
617
What might cause red or brown urine?
Haemoglobinurea, myoglobinuria, consumption of food dyes, macroscopic haematuria
618
What are the symptoms of (heavy) proteinuria?
Frothy urine, reduced plasma oncotic pressure (oedema), loss of immunoglobulins (infection), imbalanced regulators of the coagulation cascade (thromboembotic risk increased)
619
What is the normal urine protein excretion level?
Less than 150mg/24hrs (10-30mg albumin)
620
What is microalbinuria?
30-300mg albumininuria in 24hrs
| Important prognostically in diabetes
621
What is non-nephrotic proteinuria?
Defined as protein excretion of less than 3.5g/24hrs
622
What sort of kidney disease is usually associated with proteinuria?
Glomerular
623
What is the classical triad of findings in nephrotic syndrome?
Proteinuria (usually over 3.5g/24hrs)
Hypoalbuminaemia
Oedema
+ hyperlipidaemia
624
Describe the clinical presentation of nephrotic syndrome
Muehrckes bands (fingernails)
Xanthelasma
Fat bodies in urine
Oedema
625
What does classical nephrotic syndrome accompany in children?
Post-streptococcal glomerulonephritis
626
Describe the manifestation of nephrotic syndrome
```
Rapid onset
Oliguria
Hypertension
Generalised oedema
Haematuria with smoky brown urine
Normal serum albumin
Variable renal impairment
Urine contains blood proteins and red cell casts
```
627
Compare the onset of symptoms in nephrotic and nephritic syndromes
Nephrotic - insidious
| Nephritic - abrupt
628
Compare the onset of oedema in nephrotic and nephritic syndromes
Nephrotic - ++++
| Nephritic - +
629
Compare the BP in nephrotic and nephritic syndromes
Nephrotic - normal
| Nephritic - raised
630
Compare the jugular venous BP in nephrotic and nephritic syndromes
Nephrotic - ++++
| Nephritic - ++
631
Compare presence of haematuria in nephrotic and nephritic syndromes
Nephrotic - +/-
| Nephritic - +++
632
Compare the presence of red cell casts in nephrotic and nephritic syndromes
Nephrotic - absent
| Nephritic - present
633
Compare the serum albumin in nephrotic and nephritic syndromes
Nephrotic - low
| Nephritic - normal/slightly reduced
634
What is rapidly progressive glomerulonephritis?
Describes a condition/clinical situation in which glomerular injury is so severe that renal function deteriorates over days. Patient may present as a uraemic emergency with evidence of extrarenal disease
635
When do symptoms of chronic kidney disease appear generally?
Once eGFR is over 30ml/min
Even then symptoms are mild and non-specific
Most patients start dialysis with eGFR 8-10ml/min
636
Describe some symptoms of advanced kidney disease
```
Tiredness and lethargy
Breathlessness
Nausea and vomiting
Aches and pains
Sleep reversal
Nocturia
Restless legs
Itching
Chest pains
Seizures and coma
```
637
What is the clinical presentation of acute kidney injury ?
Abrupt decline in actual GFR (days-weeks). Upset of ECF volume, electrolyte and acid/base homeostasis. Accumulation of nitrogenous waste products.
638
What are the measurements that can be used to define acute kidney injury?
Increase in serum creatinine by >26.5umol/l within 48hrs
Increase in serum creatinine by >1.5 times baseline within 7 days
Urine volume <0.5ml/kg/h for 6hrs
639
What is the serum creatinine criteria for stage 1 AKI?
Increase of SCr >26umol/l
| Increase of SCr >150-200% (1.5-2fold) from baseline
640
What is the serum creatinine criteria for stage 2 AKI?
Increase of SCr >200-300% (>2-3 fold) from baseline
641
What is the serum creatinine criteria for stage 3 AKI?
SCr >354umol/l with an acute rise of >44umol/l in less than 24hrs
Increase in SCr >300% (3 fold) from baseline or initiated on RRT (irrespective of stage at time)
642
What is the urine output criteria for stage 1 AKI?
<0.5ml/kg/hr for over 6hrs
643
What is the urine output criteria for stage 2 AKI?
<0.5ml/kg/hr for over 12hrs
644
What is the urine output criteria for stage 3 AKI?
<0.3ml/kg/hr for 24hr
| Anuria for 12hr
645
What are the 3 types of AKI?
Pre-renal failure
Intrinsic renal failure
Post-renal failure
646
What is pre-renal AKI?
Actual GFR is reduced due to decreased renal blood flow.
No cell damage, so kidneys work hard to restore blood flow. Avidly reabsorption of salt and water (aldosterone and ADH release). Responds to fluid resuscitation
647
How does kidney autoregulation help prevent prevent pre-renal AKI?
Intrarenal prostacyclin high to reduce afferent tone. Effect tone high due to circulating vasoconstrictors. Of overwhelmed, AKI occurs.
648
What effect can NSAIDs have on kidney autoregulation?
Inhibit prostaglandins, so inhibit vasodilation of afferent artreriole
649
What effect can ACE inhibitors have on the kidney autoregulation?
Inhibit angiotensin 2 production, so inhibit vasoconstriction of efferent arteriole.
650
What are the 2 causes of pre-renal AKI?
Reduced effective extracellular fluid volume
| Impaired renal autoregulation
651
What might develop if the causes of poor renal perfusion is not recognised and treated promptly?
Acute tubular necrosis
652
Why is 'acute tubular necrosis' a misnomer?
Generally not necrosis, but cells damaged therefore cannot be immediately reversed. The damaged cells cannot reabsorbed salt and water efficiently, or expel excess water
653
What might cause acute tubular necrosis?
Ischaemia (depletion of cellular ATP)
Nephrotoxins
Sepsis
654
Describe the sequence of blood vessels in renal bloodflow
Interlobar arteries - afferent arterioles - glomerular capillaries - efferent arterioles - peritubular capillaries - interlobar veins
655
List some endogenous nephrotoxins
Myoglobin, urate, biliruben
656
List some exogenous nephrotoxins
X-ray contrast
Assume every drug given to patient with ATN is nephrotoxic is until proven otherwise
Drugs e.g. ACE-I, aminoglycosides, NSAIDs, ect.
657
What is rhabdomyolosis?
```
Due to muscle necrosis - release of myoglobin ('crash injury e.g. Drug users/elderly who can't move, earthquakes/disasters ect). Myoglobin is filtered at the glomerulus and toxic to tubule cells, can cause obstruction. Very dark urine.
Give forced (alkaline) diuresis
```
658
What is acute glomerulonephritis?
Immune disease affecting the glomeruli. Can be primary or secondary.
659
Describe primary acute glomerulonephritis
Disease only affects kidneys e.g. IgA nephropathy
660
Describe secondary acute glomerulonephritis
The kidneys are involved as part of a systemic process e.g. vasculitis
661
What is acute pyelonephritis?
Toxin induced - many drugs but commonest are antibiotics, NSAIDs, PPIs or bacterial infection that travels up the urinary tract.
662
Describe post-renal failure
5-10% AKI. More common in elderly. To cause AKI, obstruction must block both kidneys, or a single functioning kidney.
Obstruction with continuous urine production causes a rise in intraluminal pressure - dilation of renal pelvis (hydronephrosis) - decrease in renal function
663
How might the causes of post-renal kidney failure be grouped?
Within the lumen (kidney, ureter, bladder) e.g. Stones, blood, tumour
Within the wall (usually causes CKD, nor AKI) e.g. Congenital megaureter, stricture post TB
Pressure from outside e.g. Enlarged prostate, tumour, aortic aneurism
664
To cause AKI, what just stones be in?
Both renal pelvis or ureters
Obstruction of a single kidney
Neck of bladder
Urethra
665
Above what size will ureteric stones usually not be able to pass?
10mm
666
When might you use a USS for the urinary system?
Perform within 24hrs of presentation if obstruction is suspected as cause or AKI, or if cause is unclear
Do not need USS if cause is pre-renal/ATN unless not improving
667
When might you use a CXR for the renal system?
To look for fluid overload +- infection
668
When might you obtain a kidney biopsy?
Pre-renal and post-renal AKI ruled out
A confident diagnosis of ATN cannot be made
Systemic inflammatory symptoms/signs are present
669
How is AKI prevented?
```
Identify risk factors
Monitor 'at risk' patients
Ensure adequately hydrated
Avoid nephrotoxins
Detect early and identify cause
```
670
List some indications for dialysis
High K+ refractory to treatment
Metabolic acidosis where NaHCO3 not appropriate
Fluid overload refractory to diuretics
Presence of a dialysable nephrotoxin e.g. Aspirin OD
671
What are the signs of uraemia?
Pericarditis, reduced consciousness, intractable N&V
672
What is the prognosis of uncomplicated ATN?
Generally recovered within 2-3 wks if no superimposed insults. But hypertension on dialysis can cause additional ischaemic lesions and prolong recovery.
Mortality 30-80% (dependent on stage)
673
Define chronic kidney disease
The irreversible and sometimes progressive loss of renal function over a period of months to years.
Renal injury causes renal tissue to be replaced by extracellular matrix in response to tissue damage
674
Describe the parameters of GFR category G1
GFR >90
| Termed normal or high
675
Describe the parameters of GFR category G2
GFR 60-89
| Termed mildly decreased
676
Describe the parameters of GFR category G3a
GFR 45-59
| Termed mildly to moderately decreased
677
Describe the parameters of GFR category G3b
GFR 30-44
| Termed moderately to severely decreased
678
Describe the parameters of GFR category G4
GFR 15-29
| Termed severely decreased
679
Describe the parameters of GFR category G5
GFR <15
| Termed kidney failure
680
Define the parameters of ACR category A1
ACR <3mg/mmol
| Termed normal to mildly increased
681
Define the parameters of ACR category A2
ACR 3-30mg/mmol
| Termed moderately increased
682
Define the parameters of ACR category A3
ACR >30mg/mmol
| Termed severely increased
683
At what point does does mortality start to increase with regards to normal renal function?
25% less than normal renal function
684
What is the normal range for GFR?
80-120ml/min
685
What is the normal range for serum creatinine?
80-120umol/l
686
What percentage of renal function can be lost, and still have creatinine levels within normal range?
Up to 60%
687
What determines creatinine conc.?
Renal function and muscle mass (age, sex, race)
688
If kidneys are normal in size and cause of CKD is not obvious, what should be considered?
A renal biopsy
689
What complications might acidosis have on CKD?
May affect muscle, bone, renal function progression (makes kidneys worse).
Not generally a problem until eGFR is <20, so only in serious kidney disease
690
How might you treat acidosis in CKD?
Oral NaHCO3 tablets
691
What are some complications of anaemia in CKD?
Decreased erythropoietin production, resistance to erythropoietin, decreased RBC survival. Blood loss.
692
Describe the effect of CKD on phosphate levels, and the consequences of this.
Decreased GFR causes an increase in blood phosphate levels (as phosphate is usually excreted at the kidney). This increase in phosphate leads to a decrease in serum calcium, thus causing an increase in PTH
693
What usually happens to phosphate at the kidney?
Excretion
694
What effect does an increase in phosphate in the blood have on serum calcium?
Decrease in serum calcium (stimulating PTH production)
695
What effect does decreased GFR have on active Vit D, and the consequences of this?
Decrease in levels of active Vit D, which can lead to osteomalacia
696
What are some signs of osteodystrophy found in an X-ray?
'Rugger jersey' spine (dark stripe in X-ray of vertebrae due to loss of Ca2+)
Erosion of terminal phalanges and bone cysts
Non bone calcification
697
How might you prevent or delay progression of mineral and bone disorders in CKD?
```
Lifestyle (smoking, obesity, lack of exercise)
Treat diabetes (if present)
Treat blood pressure
ACE inhibitors/ARBs in proteinuria
Lipid lowering
```
698
When is renal replacement therapy required?
When native renal function declines to a level no longer adequate to support health. Usually when eGFR 8-10ml/min (normal ~100ml/min)
699
Give some indications for initiating dialysis
```
Uraemic symptoms
Acidosis
Pericarditis
Fluid overload
Hyperkalaemia
```
700
What are the forms of renal replacement therapy?
Dialysis - haemodialysis, peritoneal dialysis
| Renal transplant
701
When would you start renal replacement therapy?
When death is likely without it
| eGFR <15mls/min
702
What are the symptoms of end stage renal disease
Tiredness - overwhelming fatigue. Physically and mentally incapacitated. Feelings of guilt and ineptitude at needing rest.
Difficulty sleeping
Difficulty concentrating
Symptoms and signs of volume overload (SoB, oedema)
Nausea and vomiting/reduced appetite (eat less meat)
Restless legs/cramps
Pruritus (itchy skin)
Sexual dysfunction/reduced fertility
Increased infections (reduced cellular and humoral immunity)
703
What does the amount of water produced depend upon?
GFR
| ADH
704
What effect does reduced GFR have upon urine production?
Loss of the ability to maximally dilute and concentrate urine. Small glomerular filtrate but same solute load causes osmotic diuresis. Noctururia. Low volume of filtrate reduces maximum ability to excrete urine therefore maximum urine volume much smaller.
705
What bone diseases might occur as a result of kidney disease?
Hyperphosphataemia
Low 1-alpha-calcidiol
Generally asymptomatic in pre-dialysis patients (some have muscle and bone pains)
706
Why is there an increased tendency to bleed in anaemia?
Reduced platelet function
707
What effect does accumulation of waste products have in CKD?
Contributes to uraemia symptoms - reduced appetite, nausea and vomiting, pruritus
708
What might happen to dosing in a patient with ESRD/CKD?
Dose alteration required due to reduced metabolism/elimination. Drug sensitivity can be increased even if elimination is unimpaired, meaning side effects more likely e.g. Statins
709
Describe the passage of bloodflow in haemodialysis
Arterial blood - pressure monitor - pump - +anticoagulant - pressure monitor - dialyzer - airtrap & detector/pressure monitor - vein
710
What is the principles behind what goes on in a dialyzer?
Blood and dialysate move in opposite directions (countercurrent) to maximise clearance of solute through dialysis membrane
711
How often does a person on haemodialysis require dialysis?
3 times a week, 4hrs on the machine, in a designated slot.
712
What are some good points of haemodialysis?
Less responsibility than other renal replacement therapies
| You get days off treatment
713
What are some not so good points of haemodialysis?
Travel time/ waiting
You're tied to your allocated dialysis times
Big restrictions of food and fluid intake
Requires a fistula, which can be unsightly
~19 pills a day!
714
What are some contra-indications for haemodialysis?
Failed vascular access
Coagulopathy
Heart failure (can't deal with loss of blood into machine)
715
What are some possible complications of haemodialysis?
Lines - infections, thrombosis, venous stenosis
AVF - thrombosis, bleeding, access failure, steal syndrome
CVS instability
Feel chronically unwell
Accumulate morbidity (CVS, bone ect.)
716
Describe the principles of peritoneal dialysis
Peritoneum is filled with dialysate fluid. Waste products cross the semipermeable membranes (from capillaries) into the perineal space. The fluid here is then replaced. Approx 4-5 bags throughout the day, but overnight dialysis is also an option.
717
Give some positives of peritoneal dialysis
Self-sufficient/independence
Generally less fluid/food restrictions
Fairly easy to travel
Renal function may be better preserved initially
718
Give some negatives of peritoneal dialysis
Frequent daily exchanges or overnight
| You are responsible for your own care
719
Give some contraindications of peritoneal dialysis
Failure of peritoneal membrane
Adhesions, previous abdo surgery, hernia, stoma
Patient (or carer) unable to connect/disconnect
Obese or large muscle mass
~10 pills a day (significantly less than haemodialysis)
720
Give some possible complications of peritoneal dialysis
```
Peritonitis, exit or tunnel site infections
Ultrafiltration failure
Leaks (scrotal, diaphragmatic)
Development of hernia
~10 pills a day
```
721
Talk about home dialysis
```
Allows more dialysis hours
Better large molecule clearance
Patients often feel better
Patients often need fewer medications
Home HD requires someone at home with you
```
722
What are the benefits of transplant?
Reduced mortality and morbidity compared to dialysis
| Better quality of life
723
What are some drawbacks of transplant?
Peri-operative risk (mortality risk greatest for first 3 months)
Malignancy risk
Infection risk
Risk of diabetes/hypertension from meds
724
What are the different types of kidney transplant available?
Live donor (related or not)
Deceased after brain death (DBD)
Deceased after circulatory death (DCD) or non-heart beating
725
Is dialysis better for everyone?
No - patients who choose conservative care can survive a substantial length of time achieving similar numbers of hospital-free days to patients who choose haemodialysis.
Dialysis prolongs survival for elderly patients with ESRD and significant comorbidity by ~2yrs
Heart disease is especially associated with poor outcomes on dialysis
726
List some S ymptoms with ESRD with end of life care
```
Pain - related to ESRD (bone pain, dialysis-related pain). Not related (neuropathy, musculoskeletal)
Constipation
Fatigue
Nausea/lack of appetite
Pruritus
Cramps/restless legs
Sleep disturbance
```
