renal Flashcards
osmolarity =
concentration x no. dissociated particles
body fluid distribution?
2/3 ICF
1/3 ECF - 1/4 intravascular plasma, 3/4 extravascular - 95% interstitial fluid, 5% transcellular
two types of water loss?
unregulated - swear, faeces, vomit, water evaporation
regulated - renal urine production
outline positive water balance?
high water intake → ↑ ECF , ↓ Na conc, ↓ osmolarity → hypoosmotic urine production → osmolarity normalises
where is most water reabsorbed in the nephron?
PCT - 67%
loop of henle, what’s reabsorbed where?
descending limb - water passively reabsorbed 15%
thin ascending limb - nacl passively reabsorbed
thick ascending limb - nacl actively reabsorbed
outline the mechanism that optimises water reabsorption in the nephron?
countercurrent multiplication
active salt reabsorption in ascending limb→ hyperosmolar medullary interstitium → passive water reabsorption in descending limb
outline urea recycling
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
what hormone up regulates UT-A1&3 transporters? and where?
ADH on the collecting duct
where is adh produced?
supraoptic and paraventricular hypothalamic nuclei
what are the factors affecting adh production?
stimulatory: hypovolaemia hyperosmolarity hypotension nausea angiotensin II nicotine
inhibitory: hypoosmolarity hypervolemia hypertension ethanol atrial natriuretic peptide
what is the normal range for plasma osmolarity?
275-290 mOsm/kg h2o
mechanism of action of ADH?
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
which water transporters are found on the basolateral membrane of principal cells?
AQP3 and AQP4
what is diuresis?
increased excretion of dilute urine
how is NaCl reabsorbed in the thick ascending limb?
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
how is na+ reabsorbed in collecting duct principal duct?
via na+k+atpase pump
role of adh in antidiuresis?
supports na+ reabsorption
↑ na+k+cl- symporter in pct
↑ na+cl- symporter in dct
↑ na+ channel in cd
cause features and treatment of cranial DI?
decreased/no production and release of adh
polyuria and polydypsia
give external ADH
cause features and treatment of naphrogenic DI?
mutant AQP2 or v2 receptor
polyuria and polydipsia
give thiazide diuretics and NSAIDs
cause features and treatment of syndrome of inappropriate ADH secretion (SIADH)?
↑ production and release of ADH hyperosomolar urine hypervolaemia hyponatraemia give a vaptan (non-peptide inhibitor of ADH receptor)
role of kidneys in acid base homestasis?
secretion and excretion of H+
reabsorption of HCO3-
production of new HCO3-
where are most HCO3- ions reabsorbed?
PCT of nephron
outline the reabsorption of bicarbonate ions in the pct?
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
difference between a and B intercalated cells?
found in dct and cd
a = hco3- reabsorption and h+ secretion
B = hco3- secretion and h+ reabsorption
what transporters are used to move hco3- out of intercalated cells?
cl-hco3- antiporter
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
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
what are the homeostatic consequences of kidney failure?
hyperkalaemia hyponatraemia low bicarb metabolic acidosis hyperphosphataemia → pruritus salt and water imbalance
what are the endocrine consequences of kidney failure?
↓ 1-a-hydreoxcy;ase → low vitamin D → ↓ Ca2+ → high PTH
low erythropoietin → anaemia
what are the excretory consequences of kidney failure?
high urea and creatinine
reduced insulin requirement for diabetic as less is secreted
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
classic presentations of someone with renal failure?
hypovolaemia - poor skin turgor and ↓ cap refill tachypneic acidosis hyponatraemia ↑ urea and creatinine anaemia - pale lethargy anorexia
what can kidney failure lead to?
hypertension
oedema
pulmonary oedema
symptoms of hyperkalaemia?
arrythmias
vomitting
neural/muscular activity
what ecg changes would you see with hyperkalaemia?
peaked t waves wide/shorter/disappeared p waves wide QRS heart block asystole vt/vf
how can kidney failure lead to hyperparathyroidism?
kidney failure → reduced vit d levels → ↓ intestinal ca2+ absorption → hypocalcaemia → hyperparathyroidism
what are people with CKD most likely to die from?
CVD
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
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
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
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
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
normal GFR range?
≥60 ml/min/1.73m2
normal ACR?
<3 mg/mmol
normal plasma osmolality?
285 - 295 mosmol/L
most prevalent ion in ECF and conc?
sodium 140mmol/L
what part of the brain regulates sodium intake?
lateral parabrachial nucleus
sodium absorption in the nephron and %?
pct - 67 TAL - 25 dct - 5 cd - 3 excretion <1
what percentage of renal plasma enters the tubular system?
20↓
→ GFR = RPF * 0.2
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
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
what hormone inhibits renin secretion?
atrial natriuretic peptide secreted in response to atrial stretch
what stimulates the release of aldosterone? from where?
angiotensin II and ↓ BP via baroreceptors
up regulate aldosterone synthase
zona glomerulosa of adrenal cortex
what does aldosterone stimulate?
sodium reabsorption
potassium excretion
h+ excretion
what can aldosterone excess lead to?
hypokalaemic alkalosis
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
outline hypoaldosteronism?
reduced reabsorption if na+ in detail tubule → ↑ excretion of na+ and water → ECF volume falls → ↑ renin, ang II and ADH
symptoms of hypoaldosteronism?
dizziness
low bp
salt craving
palpitations (hyperkalaemia)
symptoms of hyperaldosteronism?
high blood pressure
muscle weakness
polyuria
thirst
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
low pressure baroreceptors?
in the heart, can detect low and high pressures
atria
pulmonary artery
right ventricle
high pressure baroreceptors?
vascalature only low pressure aortic arch carotid sinus JGA
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)
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
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
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
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
why carbonic anhydrase inhibitors not lead to a bigger natriuresis?
- still sodium being exchanged for bicarbonate ions
- increased reabsorption of sodium in tal, dct and cd
- macula densa detects increased tubular sodium and reduces gfr (tubuloglomerular feedback)
what acid base disturbance can carbonic anhydrase inhibitors lead to?
metabolic acidosis (less H+ being screwed into urine in exchange for sodium)
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)
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
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
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
2 examples of a k+ sparing diuretic? what else is it used to treat?
spironolactone and eplerenone
conn’s syndrome (hyperaldosteronism)
extracellular vs intracellular [k+]?
150 vs 3-5 mmol/L
which hormones stimulate k+ uptake into tissues?
insulin
aldosterone
adrenaline
what stimulates k+ secretion in the kidneys?
↑ [k+]
↑ aldosterone
↑ tubular flow
↑ plasma pH
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
what can cause hypokalaemia?
inadequate dietary intake diuretics (increase tubular flow rate) surreptitious vomitting diarrhoea genetics eg.Gitelmans syndrome
risk factors for hyperkalaemia?
k+ sparing diuretics ACE inhibitors elderly severe diabtees kidney disease
most common type of kidney cancer?
renal cell carcinoma
risk macros for kidney cancer?
smoking overweight dialysis hypertension genetics
red flag symptom for urological cancer?
painless haemturia / persistent microscopic haematuria
symptoms/signs of RCC?
hameturia
loin/flank pain
palpable abd mass
metastatic symptoms - bone pain, weight loss, haemoptysis
investigations for a pt with visible haematuria?
flexible cystoscopy
ct urogram
renal function tests
investigations for a pt with non-visible haematuria?
flexible cytoscopy
US KUB
investigations for a pt w suspected kidney cancer?
CT renal triple phase
staging - CT chest
bone scan if symptomatic
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
what other staging is used for RCC?
fuhrman grade
1-4
differentiation well to poorly
gold standard management for kidney cancer?
excision via : partial nephrectomy (if pt has single kidney, bilateral tumours, multifocal RCC, T1 tumours)
radical nephrectomy
management for kidney cancer patients unfit for surgery?
cryosurgery
mangament for patients with metastatic kidney disease/
receptor tyrosine kinase inhibitors
commonest type of bladder cancer?
transitional cell carcinoma
squamous cell carcinoma where schistosomiasis is endemic
risk factors for bladder cancer?
smoking
radiation
chronic catheterization
schistosomiasis
signs/symtpms of bladder cancer?
painless haematuria - visible/microscopic
suprapubic pain
lower urinary tract symptoms - polyuria
metastatic disease symptoms - bone pain, lower limb swelling
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
other classification method for bladder cancer?
WHO
G1 - G3
well , moderate, poorly differentiated
management for non muscle invasive bladder cancers?
transurethral resection of bladder lesion (can also be used histologically) ± intravesciular chemotherapy/ BCG immunotherapy
management for muscle invasive bladder cancers?
cystectomy
radiotherapy
±chemo
palliative
commonest typer of prostate cancer?
adenocarcinoma
risk factors for prostate cancer?
age
scandinavian
african americans
how does prostate cancer usually present?
asymptomatic unless metastatic
risk of using PSA to diagnose prostate cancer?
prostate specific but not prostate cancer specific
can be raised in UTI, prostatitis, BPH, age
investigations for prostate cancer?
blood tests for PSA
MRI
transperineal prostate biopsy
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
what other criteria can be used to grade prostate cancer?
Gleason score
2-6 = well differentiared
7 - moderate
9 - poor
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
what needs to be monitored post-prostatectomy?
PSA - should be undetectable or <0.01ng/ml
≥0.2 = relapse
side effects of prostate cancer treatment?
prostatatectomy removes proximal urethral sphincter and reduces urethral length - incontinence
risk of damage to cavernous nerves - ED
which 3 places are the ureters constricted?
pelvic ureteric junction
pelvic brim
ureterovesical juction
3 layers of ureteric tissue?
outer fibrous tissue
middle muscle layer
inner epithelium layer
3 layers of bladder tissue?
outer loose connective tissue
middle smooth muscle and elastic fibres
inner transitional epithelium
length of female vs male urethra?
3-4 cm vs 20cm
function of the prostate?
secretes seminal fluid to liquify coagulated semen
lymph nodes of bladder?
internal iliac → paraaortic nodes
lymph nodes if prostate?
internal and sacral nodes
3 parts to male urethra?
prostatic
membranous
spongy
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
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
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
types of urinary incontinence?
stress urge overflow continuous functional mixed
define stress urinary incontinence?
involuntary leakage on effort/exertion/sneezing/coughing
risk factors for stress UI?
women older age obesity smoking pregnancy and route of delivery
pathology of stress UI?
impaired bladder and urethrap support
impaired urethral closure
investigations for stress UI?
postive stress test (loss of urine on examination)
urodynamics - leakage during increase in intraabdominal pressure with absence of detrusor contraction
management of stress UI?
reduce weight
physio with PFE
Sx : mid urethral sling, colposuspension, periurethral bulking agents
risk factors for urge UI?
age prolapse increased BMI IBS bladder irritants - caffeine, nicotine
pathology of UI
involuntary detrusor contractions
idiopathic/neurogenic/bladder outlet obstruction
signs and symptoms of an overactive bladder?
urgency and frequency nocturia urgency incontinence ↓ QOL - sleep disorder, anxiety, depression enlarged prostate/prolapses
investigations for an overactive bladder?
urine dipstick - infection?
voiding diaries and post void residual
urodynamics
cystoscopy
management for overactive bladder?
lifestyle changes bladder retraining antimuscarinic drugs beta 3 agonists botox - paralyses detrusor neuromodulation sx : augmentation cystoscopy and urinary diversion
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
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
what is overflow incontinecnce?
involuntary leakage of urine when bladder is full (±due to chronic retention)
causes of overflow incontinence?
outlet obstruction eg BPH underachieve detrsuor bladder neck/urethral stricture drugs - alpha adrenegics, anticholinergics, sedatives bladder denervation post surgery
what can cause continuous incontince?
vesicovaginal fistula
ectopic ureter - straight from kidney to urethra/vagina
what is bph?
benign prostatic hyperplasia (non-malignant)
pathology of bph?
hyperplasia of lateral and median lobes → compression of urethra → bladder outflow obstruction
signs and symptoms of BPH?
hesitancy poor stream dribbling frequency nocturia ±acute retention
differentials for BPH symptoms?
bladder/prostate cancer cauda equina high pressure chronic retention UTIs prostatitis neurogenic bladder stones strictures
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)
lifestyle management of bph?
↓ weight, ↓ caffeine and fluid intake in evening, avoid constipation
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
surgical management of bph?
transurethral resection of the prostate - debunks prostate → better flow
what are the complications of bph?
progressive bladder distention → chronic retention → overflow incontinence
bilateral upper tract obstruction → renal impairment → CKD
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
what is the common active surveillance protocol for prostate cancer?
quarterly PSA testing and DREs
annual MRI with prostate biopsies
treatment options for ED resulting from prostatectomy?
PDE5 inhibitors
prostaglandin E1 injections
penile prosthesis
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
what solute has no effect on ADH?
urea
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
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
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
