renal Flashcards
(154 cards)
1
Q
osmolarity =
A
concentration x no. dissociated particles
2
Q
body fluid distribution?
A
2/3 ICF
1/3 ECF - 1/4 intravascular plasma, 3/4 extravascular - 95% interstitial fluid, 5% transcellular
3
Q
two types of water loss?
A
unregulated - swear, faeces, vomit, water evaporation
regulated - renal urine production
4
Q
outline positive water balance?
A
high water intake → ↑ ECF , ↓ Na conc, ↓ osmolarity → hypoosmotic urine production → osmolarity normalises
5
Q
where is most water reabsorbed in the nephron?
A
PCT - 67%
6
Q
loop of henle, what’s reabsorbed where?
A
descending limb - water passively reabsorbed 15%
thin ascending limb - nacl passively reabsorbed
thick ascending limb - nacl actively reabsorbed
7
Q
outline the mechanism that optimises water reabsorption in the nephron?
A
countercurrent multiplication
active salt reabsorption in ascending limb→ hyperosmolar medullary interstitium → passive water reabsorption in descending limb
8
Q
outline urea recycling
A
urea is freely filtered into the nephron via the glomerulus
in pct it is reabsorbed but in the thin descending limb it is the secreted back via the UT-A2 transporter so its concentration increases in. ascending limb and early dct impermeable to urea so concentration stays the same. in late dct urea is rebaoarbed into interstitum via UT-A3 and UT-A1 transporters to increase interstitial osmolarity and so water passively follows
9
Q
what hormone up regulates UT-A1&3 transporters? and where?
A
ADH on the collecting duct
10
Q
where is adh produced?
A
supraoptic and paraventricular hypothalamic nuclei
11
Q
what are the factors affecting adh production?
A
stimulatory: hypovolaemia hyperosmolarity hypotension nausea angiotensin II nicotine
inhibitory: hypoosmolarity hypervolemia hypertension ethanol atrial natriuretic peptide
12
Q
what is the normal range for plasma osmolarity?
A
275-290 mOsm/kg h2o
13
Q
mechanism of action of ADH?
A
bins to v2 receptor on basolateral membrane of principal cell → activates g protein which activates adenylate cyclase to produce cAMP → protein kinase A → ↑ secretion of aquaporin 2 channels → transported to apical membrane so more water can be reabsorbed
14
Q
which water transporters are found on the basolateral membrane of principal cells?
A
AQP3 and AQP4
15
Q
what is diuresis?
A
increased excretion of dilute urine
16
Q
how is NaCl reabsorbed in the thick ascending limb?
A
nakstpase pump actively transports na+ into blood → low concentration in cell → na+ moves from tubular fluid into cell with k+ and cl- via na+k+cl- symporter → k+ and cl- move put via k+cl- symporter
17
Q
how is na+ reabsorbed in collecting duct principal duct?
A
via na+k+atpase pump
18
Q
role of adh in antidiuresis?
A
supports na+ reabsorption
↑ na+k+cl- symporter in pct
↑ na+cl- symporter in dct
↑ na+ channel in cd
19
Q
cause features and treatment of cranial DI?
A
decreased/no production and release of adh
polyuria and polydypsia
give external ADH
20
Q
cause features and treatment of naphrogenic DI?
A
mutant AQP2 or v2 receptor
polyuria and polydipsia
give thiazide diuretics and NSAIDs
21
Q
cause features and treatment of syndrome of inappropriate ADH secretion (SIADH)?
A
↑ production and release of ADH hyperosomolar urine hypervolaemia hyponatraemia give a vaptan (non-peptide inhibitor of ADH receptor)
22
Q
role of kidneys in acid base homestasis?
A
secretion and excretion of H+
reabsorption of HCO3-
production of new HCO3-
23
Q
where are most HCO3- ions reabsorbed?
A
PCT of nephron
24
Q
outline the reabsorption of bicarbonate ions in the pct?
A
co2 enters cell via diffusion , combines with water in presence of carbonic anhydrase → HCO3- and H
H+ transported into tubualr fluid via Na+H+ anti porter or H+ATPase pump → H+ recombines with HCO3- to form h20 and co2 → co2 renters cell and process goes on
hco3- leaves cell via na+hco3- symporter to enter blood
25
difference between a and B intercalated cells?
found in dct and cd
a = hco3- reabsorption and h+ secretion
B = hco3- secretion and h+ reabsorption
26
what transporters are used to move hco3- out of intercalated cells?
cl-hco3- antiporter
27
how are new bicarbonate ions produced in the pct?
from glutamine breakdown which gives 2 NH4+ ions and 2 hCO3- ions
hco3- → blood
nh4+ → tubular fluid via na+NH4+ antiporter OR broken down into NH3 and H+ and moved into tubular fluid
28
how are new bicarbonate ions produced in the dct and cd?
the H+ ions secreted from a-intercalated cells combine with HPO42- ions in the tubular fluid instead of recombining with hco3- so there is a net gain of one hco3- ion
29
what are the homeostatic consequences of kidney failure?
```
hyperkalaemia
hyponatraemia
low bicarb
metabolic acidosis
hyperphosphataemia → pruritus
salt and water imbalance
```
30
what are the endocrine consequences of kidney failure?
↓ 1-a-hydreoxcy;ase → low vitamin D → ↓ Ca2+ → high PTH
| low erythropoietin → anaemia
31
what are the excretory consequences of kidney failure?
high urea and creatinine
| reduced insulin requirement for diabetic as less is secreted
32
how would the breathing of someone with kidney failure be? why?
```
tachypnoeic - kussmaul breathing
respiratory compensation for metabolic acidosis
normal o2 sats
low pCO2
high pO2
```
33
classic presentations of someone with renal failure?
```
hypovolaemia - poor skin turgor and ↓ cap refill
tachypneic
acidosis
hyponatraemia
↑ urea and creatinine
anaemia - pale
lethargy
anorexia
```
34
what can kidney failure lead to?
hypertension
oedema
pulmonary oedema
35
symptoms of hyperkalaemia?
arrythmias
vomitting
neural/muscular activity
36
what ecg changes would you see with hyperkalaemia?
```
peaked t waves
wide/shorter/disappeared p waves
wide QRS
heart block
asystole
vt/vf
```
37
how can kidney failure lead to hyperparathyroidism?
kidney failure → reduced vit d levels → ↓ intestinal ca2+ absorption → hypocalcaemia → hyperparathyroidism
38
what are people with CKD most likely to die from?
CVD
39
initial management of kidney failure?
fluid management
- hypovolaemic: give fluids
- hypervolaemic: trial diuretics/dialysis
hyperkalaemia
- move k+ into cells : sodium bicarb. / insulin dextrose
- move k+ out of body : diuretics/dialysis
- reduce gut absorption : potassium binders
40
long - term management of kidney failure?
```
erythropoietin injections - help anaemia
diuretics - for hypertension
phosphate binders - for ↑k+
1,25 vit d supplements
symptom management
```
haemodialysis
peritoneal dialysis
transplantation
41
why should transfusions sometimes be avoided in kidney disease patients?
if they're transplantable a transfusion can cause sensitisation (HLA) which can lead to transplant failure
42
what veins should be avoided in kidney failure patients why?
antecubital fossa and cephalic vein
use veins on back of hand instead
in case pt needs a fistula
43
what are the options for assessing GFR?
urea - poor indicator, confounded by diet, liver fx etc
creatinine - affected by muscle, race, sex, helpful if trend
radionuclide studies - reliable but expensive
creatinine clearance - difficult in elderly, overestimates GFR at low GFR§
inulin clearance - laborious, research only
44
normal GFR range?
≥60 ml/min/1.73m2
45
normal ACR?
<3 mg/mmol
46
normal plasma osmolality?
285 - 295 mosmol/L
47
most prevalent ion in ECF and conc?
sodium 140mmol/L
48
what part of the brain regulates sodium intake?
lateral parabrachial nucleus
49
sodium absorption in the nephron and %?
```
pct - 67
TAL - 25
dct - 5
cd - 3
excretion <1
```
50
what percentage of renal plasma enters the tubular system?
20↓
| → GFR = RPF * 0.2
51
what happens when theres high tubular sodium?
increased sodium chloride uptake by triple transporter (K+na+cl-) → adenosine released from macula dense cells → detected by extraglomerular mesangial cells → ↓ renin production → afferent smc contraction → ↓ perfusion pressure → ↓ GFR → ↓ na+ filtered and reabsorbed → ↓ tubular na+
↓ renin → ↓ angiotensin II & aldosterone
52
what promotes the reabsorption of na+?
increased sympathetic activity (from low bp) on PCT, JGA and glomerulus
increased renin → ↑ angiotensin II (PCT) → ↑aldosterone (DCT & CD)
low tubular na+ → JGA → ↑renin
53
what hormone inhibits renin secretion?
atrial natriuretic peptide secreted in response to atrial stretch
54
what stimulates the release of aldosterone? from where?
angiotensin II and ↓ BP via baroreceptors
up regulate aldosterone synthase
zona glomerulosa of adrenal cortex
55
what does aldosterone stimulate?
sodium reabsorption
potassium excretion
h+ excretion
56
what can aldosterone excess lead to?
hypokalaemic alkalosis
57
how does aldosterone work?
binds to mineralocorticoid receptor and unregulated the expression of sodium channels at apical membrane and na+k+atpase at basolateral membrane in collecting duct
58
outline hypoaldosteronism?
reduced reabsorption if na+ in detail tubule → ↑ excretion of na+ and water → ECF volume falls → ↑ renin, ang II and ADH
59
symptoms of hypoaldosteronism?
dizziness
low bp
salt craving
palpitations (hyperkalaemia)
60
symptoms of hyperaldosteronism?
high blood pressure
muscle weakness
polyuria
thirst
61
outline Liddle's disease?
inherited disease of high bp
mutation in aldosterone activated sodium channels in principal cells so it is always activated → sodium retention → hypertension
62
low pressure baroreceptors?
in the heart, can detect low and high pressures
atria
pulmonary artery
right ventricle
63
high pressure baroreceptors?
```
vascalature
only low pressure
aortic arch
carotid sinus
JGA
```
64
what happens with baroreceptors when bp is low?
reduced barorecpetor firing → afferent fibre signals to brainstem → ↑ sympathetic activity and ADH release
JGA cells activated → ↑ renin (high pressure side only)
65
what are the actions of ANP?
afferent arteriole dilation (and of other vessels) → ↑ GFR
inhibition of sodium reabsorption in pct and cd
inhibits renin and aldosterone release
↓ bp
66
what are the effects of ACE inhibitors?
vasodilation → ↑ vascular volume → ↓ BP
↓ na+ reabsorption in pct → more in distal tubule
↓ aldosterone → ↓ na+ uptake in cct → more in distal tubule
== ↓ water reabsorption → ↓ BP
67
name 5 types of diuretics and where they act?
```
osmotic diuretics - pct , mannitol
carbonic anhydrase inhibitors - pct , acetazolamide
loop diuretics - LoH tal , furosemide
thiazides - dct
k+ sparring diuretics - cd
```
68
MOA of carbonic anhydrase inhibitors?
acts n carbonic anhydrase in pct
| relies on fact that some sodium is exchanged for h+ ions which is made from carbonic anhydrase activity on h2xo3
69
why carbonic anhydrase inhibitors not lead to a bigger natriuresis?
1. still sodium being exchanged for bicarbonate ions
2. increased reabsorption of sodium in tal, dct and cd
3. macula densa detects increased tubular sodium and reduces gfr (tubuloglomerular feedback)
70
what acid base disturbance can carbonic anhydrase inhibitors lead to?
metabolic acidosis (less H+ being screwed into urine in exchange for sodium)
71
moa of loop diuretics?
inhibit triple transporter (na+-k+-2cl- symporter) in apical membrane of TAL of LoH → ↓ Na+ uptake → ↑ Na+ in distal nephron → ↓ reduced water uptake (medullary interstitial osmolality decreases)
72
moa of thiazides?
block the na-cl symporter on the apical membrane of cells of the distal tubule → less na+ reabsorption in DCT → ↑ na+ in distal tubule → less water reabsorption
73
thiazides can cause increased reabsorption of which ion? how?
calcium
as na-k-atpase still works, there is an increased na+ gradient across the basolateral membrane in distal tubule cells
in response sodium ions are transported back into cells via the na+-ca2+ anti porter - this creates a ca2+ gradient at the apical membrane so more ca2+ is reabsorbed and serum calcium levels increase
74
moa of k+ sparing diuretics?
aldosterone antagonists - prevent aldosterone form binding to the mineralocorticoid receptors on principal cells in the cortical collecting duct → ↓ ENaC and Na/K/ATPase on the apical membranes → less na+ reuptake and K+ secretion
75
2 examples of a k+ sparing diuretic? what else is it used to treat?
spironolactone and eplerenone
| conn's syndrome (hyperaldosteronism)
76
extracellular vs intracellular [k+]?
150 vs 3-5 mmol/L
77
which hormones stimulate k+ uptake into tissues?
insulin
aldosterone
adrenaline
78
what stimulates k+ secretion in the kidneys?
↑ [k+]
↑ aldosterone
↑ tubular flow
↑ plasma pH
79
how does increased flow lead to ↑ k+ secretion?
the flow bends cilia on the apical membrane who activates a PDK1 channel so more ca2+ enters the cell → ↑ ca2+ activates k+ channels so more k+ is secreted
80
what can cause hypokalaemia?
```
inadequate dietary intake
diuretics (increase tubular flow rate)
surreptitious vomitting
diarrhoea
genetics eg.Gitelmans syndrome
```
81
risk factors for hyperkalaemia?
```
k+ sparing diuretics
ACE inhibitors
elderly
severe diabtees
kidney disease
```
82
most common type of kidney cancer?
renal cell carcinoma
83
risk macros for kidney cancer?
```
smoking
overweight
dialysis
hypertension
genetics
```
84
red flag symptom for urological cancer?
painless haemturia / persistent microscopic haematuria
85
symptoms/signs of RCC?
hameturia
loin/flank pain
palpable abd mass
metastatic symptoms - bone pain, weight loss, haemoptysis
86
investigations for a pt with visible haematuria?
flexible cystoscopy
ct urogram
renal function tests
87
investigations for a pt with non-visible haematuria?
flexible cytoscopy
| US KUB
88
investigations for a pt w suspected kidney cancer?
CT renal triple phase
staging - CT chest
bone scan if symptomatic
89
TNM staging of RCC?
T1 ≤7cm
T2 ≥7cm
T3 extra renal but inside adrenal/perinephric fascia
T4 beyond perninephric fascia into surrounds
N1 met in single regional LN
N2 mets in ≥2 regional LN
M1 - distant met
90
what other staging is used for RCC?
fuhrman grade
1-4
differentiation well to poorly
91
gold standard management for kidney cancer?
```
excision via :
partial nephrectomy (if pt has single kidney, bilateral tumours, multifocal RCC, T1 tumours)
```
radical nephrectomy
92
management for kidney cancer patients unfit for surgery?
cryosurgery
93
mangament for patients with metastatic kidney disease/
receptor tyrosine kinase inhibitors
94
commonest type of bladder cancer?
transitional cell carcinoma
| squamous cell carcinoma where schistosomiasis is endemic
95
risk factors for bladder cancer?
smoking
radiation
chronic catheterization
schistosomiasis
96
signs/symtpms of bladder cancer?
painless haematuria - visible/microscopic
suprapubic pain
lower urinary tract symptoms - polyuria
metastatic disease symptoms - bone pain, lower limb swelling
97
bladder cancer TNM staging?
```
Ta - non invasive papillary carcinoma
Tis - carcinoma in situ
T1 - sub epithelial connective tissue
T2 - muscular propria
T3 - perivesical aft
T4 - prostate, uterus, vagina, bowel, abdo
```
N1 - 1 LN below common iliac bifurcation
N2 - ≥1 LN ""
M1 - distant mets
98
other classification method for bladder cancer?
WHO
G1 - G3
well , moderate, poorly differentiated
99
management for non muscle invasive bladder cancers?
transurethral resection of bladder lesion (can also be used histologically) ± intravesciular chemotherapy/ BCG immunotherapy
100
management for muscle invasive bladder cancers?
cystectomy
radiotherapy
±chemo
palliative
101
commonest typer of prostate cancer?
adenocarcinoma
102
risk factors for prostate cancer?
age
scandinavian
african americans
103
how does prostate cancer usually present?
asymptomatic unless metastatic
104
risk of using PSA to diagnose prostate cancer?
prostate specific but not prostate cancer specific
| can be raised in UTI, prostatitis, BPH, age
105
investigations for prostate cancer?
blood tests for PSA
MRI
transperineal prostate biopsy
106
TNM staging of prostate cancer?
T1 non-palpable
T2 palpable
T3 into periprostatic fat
T4 invaded onto adjacent structure
N1 pelvic LN
M1a non regional LN
M1b bone
M1x other sites
107
what other criteria can be used to grade prostate cancer?
Gleason score
2-6 = well differentiared
7 - moderate
9 - poor
108
management for prostate cancer?
young/fit + high grdae - radcial prostatectomy/radio
young/fit + low grade - active surveillance (PSA, MRI Bx)
old/unfit + high grade - hormone therapy
old/unfit + low grade - regular PSA testing
109
what needs to be monitored post-prostatectomy?
PSA - should be undetectable or <0.01ng/ml
≥0.2 = relapse
110
side effects of prostate cancer treatment?
prostatatectomy removes proximal urethral sphincter and reduces urethral length - incontinence
risk of damage to cavernous nerves - ED
111
which 3 places are the ureters constricted?
pelvic ureteric junction
pelvic brim
ureterovesical juction
112
3 layers of ureteric tissue?
outer fibrous tissue
middle muscle layer
inner epithelium layer
113
3 layers of bladder tissue?
outer loose connective tissue
middle smooth muscle and elastic fibres
inner transitional epithelium
114
length of female vs male urethra?
3-4 cm vs 20cm
115
function of the prostate?
secretes seminal fluid to liquify coagulated semen
116
lymph nodes of bladder?
internal iliac → paraaortic nodes
117
lymph nodes if prostate?
internal and sacral nodes
118
3 parts to male urethra?
prostatic
membranous
spongy
119
explain normal micturition
bladder fills and distends without rise in intravesical pressure
urethral sphincter is contracted and urethra is closed
to void bladder contracts and urethral sphincter relaxes and urethra opens
120
how does micturition vary between infants and adults?
infants : local spinal reflex where bladder empties upon reaching critical pressure
adults : voluntary control by higher centre control of external urethral sphincter keeping it closed
121
explain the innervation involved in micturition
as bladder fills M3 receptors are stimulated (PSNS S2-4)
they become stretched which leads to contraction of detrusor muscle
parasympathetic fibres also inhibit the internal urethral sphincter which causes it to relax and the urethra to open
=bladder emptying
bladder empties and stretch fibres become inactivated
→ sympathetic (T11-L2) NS is stimulated to activate beta 3 receptors causing relaxation of detrusor muscle so bladder can refill
122
types of urinary incontinence?
```
stress
urge
overflow
continuous
functional
mixed
```
123
define stress urinary incontinence?
involuntary leakage on effort/exertion/sneezing/coughing
124
risk factors for stress UI?
```
women
older age
obesity
smoking
pregnancy and route of delivery
```
125
pathology of stress UI?
impaired bladder and urethrap support
| impaired urethral closure
126
investigations for stress UI?
postive stress test (loss of urine on examination)
| urodynamics - leakage during increase in intraabdominal pressure with absence of detrusor contraction
127
management of stress UI?
reduce weight
physio with PFE
Sx : mid urethral sling, colposuspension, periurethral bulking agents
128
risk factors for urge UI?
```
age
prolapse
increased BMI
IBS
bladder irritants - caffeine, nicotine
```
129
pathology of UI
involuntary detrusor contractions
| idiopathic/neurogenic/bladder outlet obstruction
130
signs and symptoms of an overactive bladder?
```
urgency and frequency
nocturia
urgency incontinence
↓ QOL - sleep disorder, anxiety, depression
enlarged prostate/prolapses
```
131
investigations for an overactive bladder?
urine dipstick - infection?
voiding diaries and post void residual
urodynamics
cystoscopy
132
management for overactive bladder?
```
lifestyle changes
bladder retraining
antimuscarinic drugs
beta 3 agonists
botox - paralyses detrusor
neuromodulation
sx : augmentation cystoscopy and urinary diversion
```
133
why would antimuscarinic drugs be given in urge incontinence?
it is M3 receptors that are stimulated when the ladder fills and distends - this activates the PSNS so the detrusor contacts and the inter sphincter relaxes to empty the bladder
blocking these receptors would inhibit this process to reduce incontinence
134
why would beta 3 agonist drugs be given in urge incontinence?
beta 3 receptors part of the sympathetic nervous system are responsible for relaxing the detrusor muscle while the bladder fills and for contracting the internal urethral sphincter keeping the urethra closed - beta 3 agonists would upregulate this process and prevent the bladder emptying
135
what is overflow incontinecnce?
involuntary leakage of urine when bladder is full (±due to chronic retention)
136
causes of overflow incontinence?
```
outlet obstruction eg BPH
underachieve detrsuor
bladder neck/urethral stricture
drugs - alpha adrenegics, anticholinergics, sedatives
bladder denervation post surgery
```
137
what can cause continuous incontince?
vesicovaginal fistula
| ectopic ureter - straight from kidney to urethra/vagina
138
what is bph?
benign prostatic hyperplasia (non-malignant)
139
pathology of bph?
hyperplasia of lateral and median lobes → compression of urethra → bladder outflow obstruction
140
signs and symptoms of BPH?
```
hesitancy
poor stream
dribbling
frequency
nocturia
±acute retention
```
141
differentials for BPH symptoms?
```
bladder/prostate cancer
cauda equina
high pressure chronic retention
UTIs
prostatitis
neurogenic bladder
stones
strictures
```
142
investigations for BPH?
```
urine dip
post void residual
voiding diary
bloods - PSA (predict prostate volume)
US
urodynamics and flow studies
cystoscopy (if worry about cancer)
```
143
lifestyle management of bph?
↓ weight, ↓ caffeine and fluid intake in evening, avoid constipation
144
medical management of bph?
alpha blocker - block alpha 1-AR on prostate and bladder neck smooth muscle → relaxation → improved urinary flow rate
5- alpha reductase inhibitors - prevent conversion of testosterone to DHT (promotes growth of prostate) → shrinkage → improved flow rate and less obstructive symptoms
145
surgical management of bph?
transurethral resection of the prostate - debunks prostate → better flow
146
what are the complications of bph?
progressive bladder distention → chronic retention → overflow incontinence
bilateral upper tract obstruction → renal impairment → CKD
147
why is imaging favoured over biopsies in suspected prostate cancer?
random biopsies were associated with under detection of high grade cancer and over detection of low grade cancer
148
what is the common active surveillance protocol for prostate cancer?
quarterly PSA testing and DREs
| annual MRI with prostate biopsies
149
treatment options for ED resulting from prostatectomy?
PDE5 inhibitors
prostaglandin E1 injections
penile prosthesis
150
how does liver cirrhosis lead to high urine osmolarity?
hepatic cirrhosis → vasodilation → ↓ systemic vascular resistance → ↓ BP → ↑ ADH secretion → more water reabsorbed and less excreted via urine → ↑ urine osmolarity ↓ hyponatraemia
151
what solute has no effect on ADH?
urea
152
compare hemodialysis with peritoneal dialysis
```
haemodyalysis:
usually dialysis centre visits
3-4.5 hrs 3x/week
strictly dietary constraints
salt water restrictions
arteriovenous fistula or tunneled central venous line (risk of infection)
```
```
peritoneal dialysis:
at home
7 days/week
less food/water constraints
can travel easily
can be done anywhere
risk of peritonitis
```
153
what factors are considered for being a live kidney donor?
fHx of kidney disease
age
comorbidities
kidney match - blood type, HLA typing, serum crossmatch
future pregnancy?
mental health
2 healthy kidneys - size, eGFR, no haem/proteinuria
154
recommendations for post transplant success?
minimise risk 9f diabetes, CVD, cancer and psychiatric disorders
low sugar and salt diet
no smoking, NSAIDs, live vaccines, drugs
avoid seville oranges - interact w immunosuppressants
no raw meat, eggs, fish
