Renal Flashcards
Risk factors for kidney cancer?
Smoking Renal failure and dialysis Obesity Hypertension Von Hippel-lindau syndrome(50% develop RCC)
How does the low pressure side of the CVR system respond to high and low pressure?
Low pressure -> reduced baroreceptor finding -> signalling to CNS (medulla) -> increase sympathetic activity (and ADH release)
High pressure -> more Atrial stretch ->ANP, BNP released
How can the body decrease sodium reabsorption?
- Via Atrial natriuretic peptide
2. Via a decrease in B1-sympathetic activity. Thus decreased activation of RAAS
describe the lymphatic drainage of the prostate
obturator nodes -> internal iliac chain.
OAB is a syndrome of?
Frequency, urgency, nocturia with or without leak
State the signs and symptoms of hypoaldosteronism
ECF volume decreases
increased renin, Ang II and ADH :
- low blood pressure
- dizziness
- salt craving
- palpitation
in what setting do ACE inhibitors need to be paused as they can worsen GFR? how does it cause this?
in an acutely unwell patient
reduces perfusion pressure in the glomerulus
how do you treat urge incontinence?
Decrease caffeine, stop smoking, lose weight
Bladder retraining, pelvic floor muscle exercises
Drugs to promote detrusor muscle relaxation:
- Anticholinergics/antimuscarinics - solifenacin, tolterodine, trospium
- Beta-3-agonists - betmiga
How do carbonic anhydrase inhibitors work?
- Reduced production of carbonic acid
- Thus reduced production of H+
- Reduction in exchange of H+ for Na+
- Reduced Na+ reuptake in the PCT
- Increased Na+ in distal nephron
- Reduced water reabsorption
How do osmotic diuretics work?
Don’t get reabsorbed
Increases osmolarity in PCT -> less water reabsorbed
Intravenous fluid or oral fluid first enters the __ and then enters the __ compartment
ECF then equilibrates with ICF
ADH promotes water reabsorption from ___ __ of kidney
Collecting duct
Binds to V2 Receptor -> AQP2 inserted apical and AQP3 into basolateral membrane
What are the consequences of salt and water retention in kidney failure?
hypertension, HF, pulmonary oedema
What protein does ADH affect to alter water reabsorption?
aquaporins
why is there high blood pressure in Liddle’s Syndrome?
- Mutation in aldosterone activated sodium channel (ENAC)
- Channel is always “on” -> sodium retention = water retention
- aldosterone is normal or low *
in a 59 year old man, what would be first line treatment for hypertension?
Which other group of people have this as first line?
Aged >55 = Amlodipine. (CCB)
African Americans
How do kidneys typically appear on ultrasound in acute renal failure with no obstruction?
normal size
How can the body retain sodium & water
- Sympathetic activity:
- stimulates sodium uptake by cells of PCT
- makes smooth muscle cells of afferent arteriole (AA) contract.
- Stimulates cells of JGA to secrete Renin. resulting angiotensin II makes PCT take up sodium and resulting aldosterone makes DCT and CT take up sodium - low tubular Na+ stimulates renin production by JGA
risk factors for bladder cancer?
Smoking
Occupational exposure (aromatic hydrocarbons) e.g. working with dyes
Chronic inflammation of bladder (bladder stones, schistosomiasis, long term catheter)
Drugs (cyclophosphamide)
Radiotherapy
what are the symptoms of metabolic acidosis seen in kidney failure?
Anorexia
Muscle catabolism
A patient suffering from hepatic cirrhosis will have a ___ urine osmolarity
high
leakage associated with urinary retention is?
overflow incontinence
A respiratory Acid-base disorder is determined by looking at _ levels
PCO2
state 4 conditions patients are at risk of post kidney transplantation
Diabetes
Cardiovascular disorders
Cancer
Psychiatric disorders
Post prostatectomy, a PSA of ____indicates a relapse
> 0.2
risk factors for urine incontinence?
Increasing age Drugs e.g. ACE inhibitors Pregnancy and vaginal delivery Smoking Obesity Family history Constipation prolapse/hysterectomy/menopause
Mr. Holmes is being treated with a loop diuretic and Mr Smith with a thiazide diuretic for the past 3 weeks. Both individuals are drinking insufficient amount of water. Whose urine will have a lower osmolarity and why?
Mr. Holmes - because loop diuretics act on loop of Henle whilst thiazide diuretics act on distal convoluted tubule.
risk factors for prostate cancer?
Increasing age
Western nations (scandinavian countries)
African americans
The excretion of which major ions/molecules is altered to correct volume expansion and how is it affected?
Sodium and water
Their reabsorption is reduced
What is the mechanism/3 causative theories for stress incontinence in men?
Sphincter incompetence
Reduction in urethral sphincter length
Postoperative stricture
why might a patients use of trimethoprim invalidate the GFR calculator?
Trimethoprim inhibits active secretion of creatinine, causing creatinine to rise.
GFR may not have actually changed but you need further tests to know for sure
what tests are carried out for BPH?
Digital rectal exam
Urine test - rule out infection/other causes
PSA - will be elevated in BPH
Flow rate + PVR
State 5 causes of hyperkalemia
- K+ sparing diuretics
- ACE inhibitors
- Elderly
- Severe diabetes
- Kidney disease
state 3 types of acute renal failure and their pathophysiology
- Prerenal - insufficient blood flow to kidneys e.g. hypovolemia
- Intrinsic renal failure - filtration problem e.g tubulointerstitial disorders
- Postrenal - bilateral outflow obstruction
the complaint of an involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing is?
mixed urinary incontinence
What is the main intracellular ion? (it is low in extracellular fluid)
K+
PISO -Potassium inside and sodium outside
how do you manage CKD?
Initial -> Correct fluid balance - if hypo give fluids, if hyper give diuretic/dialysis
Initial -> Reverse hyperkalemia:
Drive into cells - sodium bicarb or insulin dextrose
Drive out of body - diuretics/ dialysis
Gut absorption - potassium binders
Long term - hemodialysis or peritoneal dialysis at home OR in centre hemodialysis
Kidney transplant
advantages of peritoneal dialysis
Less food and water constraints
Can travel easily
In what parts of the nephron is K+ secreted?
DCT and Collecting duct
Only reabsorbed in these regions if you are K+ depleted
State 4 things that stimulate potassium secretion in the nephron?
- High plasma K+ (more K+ enters cell via Na/K+ ATPase and leaves via lumen)
- high plasma pH
- Increase in tubular flow rate
- Increase in aldosterone
What is the most prevalent and important solute in the ECF?
sodium
Incidence of prostate cancer is _____ but mortality rates ____
rising
declining
the complaint of an involuntary leakage accompanied by or immediately preceded by urgency is?
urge incontinence
What part of the nephron would a diuretic drug that inhibits the activity of an enzyme found predominantly in the endothelial cells of the lung work?
Whole renal tubular system except in loop of henle
Due to lack of angiotensin II AND Aldosterone
A metabolic Acid-base disorder is determined by looking at _ levels
HCO3-
what are some differential diagnosis for urge incontinence?
UTI DO Urethral syndrome Urethral divertivulum Interstitial cystitis Bladder cancer Large residual volume
How does the high pressure side of the CVR respond to low pressure?
Low pressure -> reduced baroreceptor firing -> signalling to brainstem -> sympathetic activity and ADH release
Low pressure -> reduced baroreceptor firing -> JGA cells -> renin release
___ have a higher prevalence of OAB-wet and ___ have a higher prevalence of OAB-dry
women
men
function of prostate
liquify ejaculate
prostate cancer investigations?
PSA (not prostate-cancer specific but prostate specific). Can be elevated in UTI, prostatitis
MRI
Trans perineal prostate biopsy
If a kidney leaks contrast up into it on an Xray, it means that it is __
faulty
continuous leakage is?
continous incontinence
what does conservative treatment of CKD involve?
erythropoietin injections to correct anaemia diuretics to correct salt water overload phosphate binders 1.25 vit d supplements symptom management
clinical features of bladder cancer?
PAINLESS haematuria or persistent microscopic haematuria
Suprapubic pain
Lower urinary tract symptoms e.g. increased frequency
Metastatic disease - bone pain, lower limb swelling
what are some symptoms of AKI?
Decreased urine output, although occasionally urine output remains normal
Fluid retention, causing swelling in your legs, ankles or feet
Shortness of breath
Fatigue Confusion Nausea Weakness Irregular heartbeat Chest pain or pressure
Seizures or coma in severe cases
Incidence and mortality of bladder cancer in UK is ___
declining
the complaint of loss of urine during sleep is?
nocturnal enuresis
What is spironolactone used for and what is its mechanism?
- Can be used to treat hypertension (not first-line)
- It is an aldosterone receptor blocker in the DCT
what causes BPH
↑ number of epithelial and stromal cells in the periurethral area of the prostate in response to androgens (testosterone)
treatments for stress incontinence?
weight loss, kegel exercises, cessation of smoking
oestrogen therapy if evidence of atrophy
Surgery - occlusion, supportive e.g. mid-urethral sling, ileal conduit diversion
the complaint of involuntary leakage on exertion /sneezing/coughing is?
stress incontinence
what are the symptoms of hyperkalemia?
Cardiac arrhythmias
Neural and muscular activity
Vomiting
Outside the CNS, where else is sodium regulated?
through taste
What are the types of kidney cancer in order of frequency?
85% is renal cell carcinoma (adenocarcinoma)
10% transitional cell carcinoma
sarcoma/Wilms tumour/other subtypes = 5%
*incidence and mortality is rising. 7th most common cancer in UK
what treatment is carried out for BPH?
alpha-adrenergic antagonists - amsulosin, alfuzosin, doxazosin. They relax urinary sphincter and allow you to pee
5-alpha-reductase inhibitors - Finasteride, Dustasteride
Surgery - TURP, embolisation
What is the effect of increasing ANP/BNP on GFR?
increases GFR due to vasodilation
The low pressure side of the cardiovascular system contains baroreceptors where?
Heart - atria, right ventricle
Vascular system - pulmonary vasculature
what are the McNeal’s zones of the prostate?
Transitional zone Central zone (25%) Peripheral zone (65% glandular tissue)
how does angiotensin II make aldosterone?
Stimulates the synthesis of aldosterone synthase in the zona glomerulosa of adrenal gland
what is the result of increased dietary sodium?
increased water intake and retention -> increased ECF volume -> increased blood pressure and volume
what are the types of prostate cancer?
> 95% adenocarcinoma
what hormone is responsible for prostate development?
DHT
clinical features of prostate cancer?
Usually asymptomatic unless metastatic
What is the effect of plasma concentration of urea on ADH production?
No effect
Bladder cancer subtypes in order of frequency?
> 90% = transitional cell carcinoma
1-7% = squamous cell carcinoma but 75% SCC where schistosomiasis is endemic
2% = Adenocarcinoma
In which type of kidney failure might a patient not present with aneamia?
acute -> has not had time to develop
symptoms of BPH?
↓ urinary flow, urinary frequency, urgency and nocturia
Why do most diuretics increase potassium excretion?
The increase in flow rate is detected in the collecting duct and directly stimulates potassium excretion
Give two examples of Drugs eliminated by kidney and will lead to side effects if kidney function is impaired
Morphine, metformin
state 2 things that trigger aldosterone synthesis
- Angiotensin II
2. Decrease in bp detected by baroreceptors
normal range for HCO3-?
22-28 mmol/L
If a patient is dehydrated, the filtrate in which area will have the highest osmolarity?
Tip of loop of Henle
normal range for pH?
7.35-7.45
What is the effect of a mutant UT-B urea transporter on urine osmolality?
decreases
What stimulates plasma K+ uptake into tissues? How?
INSULIN mainly -> increases intracellular sodium which is exchanged for K+
(also aldosterone and adrenaline)
why can ibuprofen worsen GFR?
inhibits PG synthesis.
So no prostaglandins to dilate afferent arterioles.
renal blood flow decreases
Why does an increase in flow rate cause K+ secretion?
cells have cilia that stimulate PDK1 which increases Ca2+
concentration in the cells which stimulates opening of K+ channels
___ is an example of a loop diuretic
furosemide
associations for stress incontinence?
Obesity
Vaginal delivery
Prostate surgery
what are the side effects of a prostatectomy?
Damage to cavernous nerves = ED
Damage to cavernous nerves, removal of proximal urethral sphincter and changes urethral length = urinary incontinence
What is the effect of aldosterone on Na+, H+ and K+
Increased Na+ reabsorption by increasing permeability of the principal cells
Increased H+ and K+ secretion (hypokalemic alkalosis if in excess)
What is the most abundant adrenoceptor subtype in the prostate?
alpha-1-a
How do potassium sparing diuretics work?
Bind to mineralocorticoid receptor and block aldosterone function in collecting duct
Potassium sparing because DOES NOT pump K+ out into lumen
Example = spironolactone
state 3 ECG changes that can be seen in hyperkalemia
Peaked T waves P wave - broadens -> reduced amplitude -> disappears QRS widening Heart block Asystole VT/VF
where is sodium reabsorbed in the nephron?
67% in PCT
25% in thick ascending limb
5% DCT
3% in collecting duct
How do you manage kidney cancer?
Partial nephrectomy (single kidney, bilateral tumour, multifocal RCC in patients with VHL, T1 Tumours up to 7cm)
Radical nephrectomy
Patients with small tumours unfit for surgery - cryosurgery
Metastatic disease - receptor tyrosine kinase inhibitors
What changes occur in terms of lab values during kidney failure?
Homeostatic dysfunction - ↑ potassium ↓ bicarbonate ↓pH ↑phosphate, Na+ and water imbalance
Endocrine dysfunction - anemia (erythropoeitin deficiency), 1 alpha-hydroxylase vitaminD deficiency (↓calcium, ↑PTH - hyperparathyroidism)
Excretory dysfunction - ↑Urea, ↑Creatinine, ↓insulin clearance
Impaired glucose metabolism - decreased insulin clearance, decreased gluconeogenesis
AKI causes a _ in BUN and Cr.
rise
What is the mechanisms/5 causative theories for stress incontinence in women?
Urethral position theory Intrinsic sphincter deficiency Integral theory Hammock theory Trampoline theory
what blood gas values and other blood values would you expect in a renal failure patient?
Urea - high Creatinine - up K+ - high Na+ - varies Hb - low
Blood gas: pH - down pCO2 - down PO2 - slightly up Bicarbonate - down Base excess - down
the complaint of an involuntary loss of urine immediately after passing urine is called?
post-mictruition dribble
In which region of the nephron do loop diuretics work?
TAL
Effect of high EXTRAcellular K+
Depolarisation of membranes -> APs, heart arrhythmias
disadvantage of peritoneal dialysis?
Normally 7 days a week
Chance of infection due to catheter
In which region of the nephron do carbonic anhydrase inhibitors work?
PCT
clinical features of kidney cancer?
PAINLESS haematuria or persistent microscopic haematuria (red flag symptom. also for any other urological malignancy)
Loin pain
Palpable mass
Metastatic disease - Bone pain, hemoptysis
Why do patients with chronic renal failure have an increased cardiovascular risk?
hypertension, dyslipidemia
What would be the effect of water reabsorption of increased sodium levels reaching the collecting duct?
Less water reabsorbed at collecting duct due to reduction of osmotic gradient
The kidney not only secretes H+ and reabsorbs HCO3-, it also ____ HCO3-
produces
A ___ __ of bladder lesions uses heat to cut out all visible tumours. It provides histology and can also be curative
transurethral resection
When there is euvolemia, sodium intake is ___. This is achieved through cells responding to the neurotransmitters, ___ and ____.
inhibited
serotonin and glutamate
How do kidneys typically appear on Ultrasound in CKD?
shrunken
State 5 causes of Hypokalemia
- Inadequate dietary intake - too much processed food
- Diuretics (increased tubular flow rates)
- Surreptitious vomiting
- Diarrhoea
- Genetics - Gitelman’s Syndrome (mutation in the Na/Cl transporter in the distal nephron)
What would be the effect of spironolactone treatment on a patient with Liddle’s Syndrome?
- No effect
- The mutation in Liddle’s syndrome is in the aldosterone sensitive ENaC sodium channel. This mutation means that the channel is always on
describe the venous drainage of the penis
peri-prostatic venous plexus -> internal iliac vein
How do thiazide diuretics work?
Block Na+ Cl- transporter in the DCT
Increases calcium reabsorption as a side effect
when is atovarstatin offered to patients?
offers atorvastatin if >10% risk of CVD within 10 years. You may need the QRISK3 tool
In which type of acute kidney injury would you see salt and water loss as opposed to the typical salt and water retention in renal failure?
intrinsic renal failure
When there is sodium deprivation, appetite for Na+ is ___ and this is driven by ___ and ____.
increased
GABA and Opioids
Why might a patient with kidney failure be tachypneic with normal o2 stats and clear lungs on auscultation?
metabolic acidosis -> Kausmall respiration
A patient with CKD secondary to hypertension is taking amlodipine. his BP is controlled well (125/70) but he now has significant proteinuria (ACR >30).
What treatments should the nephrologist initiate for the proteinuria and what treatment might need to be stopped?
Drugs to initiate which improve proteinuria:
- ACEi or ARB
- SGLT2 inhibitors e.g dapagliflozin
- Salt restriction
Stop Amlodipine if the ACEi reduces his BP too low
_ recycling and NaCl are both responsible for generating a hyperosmotic medullary interstitium
urea
What is the normal range for PCO2?
33-45 mmHg
Effect of high INTRAcellular K+
Depolarisation more difficulties -> heart arrhythmias and asystole
what are the investigations for kidney cancer?
Painless visible haematuria:
- Flexible cystoscopy
- CT urogram
- Renal function
Persistent microscopic haematuria:
- Flexible cystoscopy
- US KUB
Suspected kidney cancer:
- CT renal triple phase
- Staging CT chest
- Bone scan if symptomatic
What part of the nephron would a diuretic drug that inhibits the release of an extracellular enzyme from the kidney into the plasma work?
JGA - extracellular enzyme would be renin
In which region of the nephron do thiazide diuretics work?
DCT
As arterial pressure increases, what happens to GFR? Why?
Increases then eventually plateaus:
- High tubular sodium
- Increased sodium/chloride uptake via triple transporter
- Adenosine release from Macula Densa cells
- Detected by extraglomerular mesangial cells
- Reduces renin production
- Promotes afferent SMC contraction
- Reduces perfusion pressure and so GFR
In which region of the nephron do K+ -sparing diuretics work?
CT/collecting duct
management of prostate cancer?
If young and fit and HIGH grade cancer = Radical PROSTATECTOMY/Radiotherapy
Young and fit and LOW grade cancer = active surveillance
If old/unfit and High grade cancer/metastatic = hormone therapy
If old/unfit +low grade cancer = watchful waiting, regular PSA testing
state the signs and symptoms of hyperaldosteronism
ECF volume increases
reduced renin, AngII and ADH
Increased ANP and BNP:
- high blood pressure
- muscle weakness
- polyuria - because you are drinking more water
- thirst
How do loop diuretics work?
Block Na+ Cl- K+ triple transporter in TAL
investigations for bladder cancer?
Painless visible haematuria:
- Flexible cystoscopy
- CT urogram
- Renal function
Persistent microscopic haematuria:
- Flexible cystoscopy
- US KUB
If biopsy proven muscle invasive then start staging investigations
what are 2 obstruction induced changes as a result of BPH?
Detrusor instability/↓ compliance → frequency and urgency - storage problem
↓ detrusor contractility -> increased residual urine, hesitancy - voiding problem
State 3 reasons why ACE inhibitors lower BP
Vasodilation
Renal effect - decreased Na+ reuptake in PCT = increased Na+ in the distal nephron = reduced water reabsorption
Adrenal effect - reduced aldosterone = decreased Na+ uptake in CT = increased Na+ in distal nephron
how do you treat erectile dysfunction?
PDE5 inhibitors like viagra
what are some investigations for urinary incontinence?
Urine dipstick
Flow rate and post-void residual
Bladder diary
Pad tests
The high pressure side of the cardiovascular system contains baroreceptors where?
Vascular system - carotid sinus, aortic arch, juxtaglomerular apparatus
what 2 things contribute to hypocalcemia in chronic renal failure
Phosphate retention
Low levels of 1-25 VitaminD
How does aldosterone make the DCT and CT take up sodium?
- Binds to mineralocorticoid receptor in cell cytoplasm
- Receptor dimerises and binds to DNA in nucleus leading to production of mRNAs
- ENaC and Na+K+ATPase and regulatory proteins synthesised
what is the most common cancer within men in the UK?
prostate cancer
Negative water balance is when you have __ water intake
low
disadvantage of heamodyalisis?
Strict dietary constraints and salt/water intake restrictions
Requires dialysis centre visits
describe the arterial blood supply to the prostate
Arises from branches of the inferior vesical artery
Prostatic artery divides into urethral and capsular groups of arteries
Urethral group give rise to Flock’s and Badenoch’s arteries
Describe the mechanism of ANP
Dilates afferent arterioles (and constricts efferent arterioles) -> causes increase in GFR and Na+ filtration.
Also Decreases Na+ reabsorption in renal collection duct
Net result = Na+ and volume loss
(counters raas system)
How does angiotensin 2 affect production of aldosterone?
Increased synthesis of aldosterone synthase in the zona glomerulosa which is required for conversion of cholesterol to aldosterone and therefore increased aldosterone
What is the effect of increased sympathetic activity on RAAS system?
Increases renin/ Raas activity
Which cells secrete renin?
JG cells
All diuretics except K+ sparing diuretics ___ K+ excretion. Thus they cause ___
Increase
Hypokalemia
Carbonic anhydrase inhibitors and K+ sparing diuretics both cause metabolic ___. Other diuretics cause metabolic ____ via RAAS and contraction ____.
Acidosis
Alkalosis
Alkalosis
What are the effect of loop and thiazide diuretics on calcium?
Loop diuretics - hypocalcemia
Thiazide diuretics - hypercalcemia
