Urinary Flashcards
What are symptoms of end stage renal disease?
N+V, Fatigue, Anorexia, Weight loss, Muscle cramps, Pruritis, Lower extremities uncomfortable and swollen, Dry cough, SOB
What is the main reason why patients have symptoms during end stage renal disease?
Hyperuricaemia
Loss of fluid, electrolyte and pH homeostasis
Loss of endocrine functions of kidneys
What are signs of end stage renal disease?
Tachypnoea Tachycardia HTN Dry skin - uraemic frost Petechia Moist rales posterior lung bases S3 on cardiac exam Abdominal exam - benign Pitting oedema MSK pain
What are the stages of CKD?
1 -4
5 is ESRD
What is a long term problem with the endocrine function in ESRD?
Anaemia
90% of EPO made by interstitial peri-tubular cells
Response to cellular hypoxia
Vit D deficiency
Proximal tubule cells - produce 25-hydroxyvitamin D-1 alpha-hydroxylase -> Activates Vit D -> Functionally Vit D deficient
What are common symptoms of diabetes?
Polyuria Polydipsia Pruritis Weight loss FMHx of DM Diet, smoking, eye symptoms (retinopathy) Fungal infections Poor wound healing Sensation in feet - peripheral neuropathy
Where are the kidneys located and what is their approximate size?
Located retroperitoneal Long axis parallel to psoas muscle Bean shaped Height of 3 vertebral bodies Between T11-T12 is their mid point so sits below the ribs and in the abdomen
At what time in development do the kidneys ascend to their final position?
Week 8
Why can patients get a horse-shoe kidney?
Gets caught on the aorta and the bottoms fuse to prevent it moving further up
What imaging modalities can be used for the kidneys?
Ultrasound, x-ray, CT, MRI Renal doppler Renal scintigraphy (gamma scanner)
What size urolithiasis would require intervention?
> 6mm
What are 2 methods of treating a urolithiasis?
Extracorporeal Shock-Wave Lithotripsy (ESWL) Percutaneous nephrolithotomy (PCNL)
What stone size would deem extracorporeal shock-wave lithotripsy unsuitable?
> 2cm
Lower pole calyx
Radiolucent
Body habitus/ weight
What can cause a PUJ obstruction?
Idiopathic - congenital
Retroperitoneal fibrosis
Secondary to trauma or infection
If someone presents with pain after alcohol consumption in the flank what could that indicate?
PUJ obstruction
When do you use DMSA and MAG3?
DMSA - renal function test - accumulates in renal cortical tubules and cortex
MAG3 - renal function and structure
What is TNM staging for urothelial carcinoma?
T1 - through lamina propria
T2 - through lamina propria + into the inner muscle layer
T3a - through above + into the outer muscle layer
T3b - through above + outer muscle layer
T4a - through all bladder layers and to nearby structures - pelvis etc
T4b - through all bladder layers + through prostate gland
What are indications for a nephrostomy?
Relieve urinary tract obstruction especially if urosepsis
Urinary diversion
PCNL access or access for alkanisation of stones
Delivery of chemo
Through which embryonic layer does the kidney develop from?
Intermediate mesoderm
What two structures make up the embryonic kidney?
Mesonephric tubules and mesonephric duct
What structure drives the development of the true kidney in the embryo?
Ureteric bud
If the ureteric bud fails to interact with the intermediate mesoderm what is the potential result?
Renal agenesis
Can have unilateral but bilateral is not compatible with life
What is the urachus and what is a potential problem at birth?
Urachus connects foetal bladder to the umbilicus called the allantois. If it is patent after birth then the urine can still keep coming out of the umbilicus
What does the urorectal septum become after development?
Perineum at the base -> pouch of douglas/ rectovesicle pouch
What does the urogenital sinus develop into?
Superior parts -> umbilicus
Majority -> urinary bladder
Inferior parts -> urethra
What 4 parts is the urethra divided into?
Pre-prostatic (bladder to prostate)
Prostatic
Membranous
Spongy
What is hypospadias?
Defect in the fusion of the urethral folds
Urethra opens onto the ventral surface rather than at the end of the glans penis
Define GFR?
GFR - glomerular filtration rate
Amount of filtrate that is produced from the blood flow per unit time
What is the normal GFR?
90-120mls/min/1.73m2
What is the normal total glomerular filtrate per day?
140-180litres/day
What does GFR depend on?
Age Gender Size of individual Size of kidneys Pregnancy
What is the GFR at birth?
~20ml/min/1.73m2
Normalises by ~18months
How does GFR change with age?
> 30 years of age - GFR declines 6-7ml/min/ decade
How does GFR change in pregnancy?
GFR increases to 130-180ml/min
Kidney size increases too ~1cm growth
What 2 reasons in simple terms would point to a decrease in GFR
Decline in number of nephrons
Decline of GFR within individual nephrons (GN, diabetes, HTN)
How do you measure clearance through the kidneys?
Clearance (ml/min) = Amount of substance eliminated per unit time (mg/min) / Plasma conc of substance (mg/ml)
Alternatively:
Renal clearance = excretion rate / plasma conc
Excretion rate = amount in urine X urine flow rate
What 4 factors would lead to the best substance to measure for renal clearance calculation?
1 - produced at a constant rate
2 - freely filtered across glomerulus
3 - not reabsorbed in the nephron
4 - not secreted into the nephron
What 3 exogenous substance can be used to determine renal clearance?
1 - Inulin clearance
2 - 51 Cr-EDTA = radio active labelled marker
3 - Iohexol - contract agent
What endogenous substance can be used to determine renal clearance?
Creatinine
What is the problem with creatinine being used as a marker for renal clearance?
It is secreted into the renal tubule so shows a 10%-20% overestimation of the renal clearance
Cumbersome as 24hour clearance measurement
What is the normal serum creatinine level?
70-150micromol/litre
What 2 main factors affect creatinine levels in an individual?
Protein intake Muscle mass Age Gender Race - black higher creatinine, hispanic/ indo-asian lower Drugs - trimethoprim
What are the variables used in the MDRD GFR calculator
Serum creatinine
Age
Sex
Caucasian or black
When is MDRD GFR inaccurate?
People without kidney disease Children Pregnancy Old age Other ethnicities When true GFR changes quickly - AKI
Why is eGFR less accurate with mild kidney disease?
1 - reduction in GFR
2 - rescued nephron number -> nephron hypertrophy -> GFR same
3 - Increased serum creatinine -> increased secretion into the tubule
What does nephrogenic autoregulation mean?
Controlling the GFR within physiological blood pressure limits by the myogenic response and the tubuloglomerular feedback systems.
Which nephrons undergo autoregulation?
Cortical nephrons
Which nephrons have AA>EA and which have AA=EA?
AA>EA= Cortical AA=EA = Juxtamedullary
Which nephrons have a higher concentration of renin?
Cortical
Much higher as they have a higher response to RBC due to their differing arteriolar sizes they can control BP more effectively with the release of renin
What cells create the filtration barrier?
Podocytes
Acellular gelatinous layer of glycoproteins that are negatively charged - aka basement membrane
Slits allows fluid to leave through the capillary membrane
How does charge affect the filtration of substances in the kidney?
Basement membrane is negatively charged
Small but negatively charged molecules - not cleared
Large but positively charged molecules can still get through
What causes the ultra filtrate to be produced?
Hydrostatic pressure within blood > oncotic pressure within blood
Oncotic pressure within blood = Hydrostatic pressure within the bowman’s capsule
What is the myogenic response in the kidneys?
Arterial smooth muscle responses to increases and decreases in vascular wall tension - property of preglomerular resistance vessels
What is tubuloglomerular feedback?
[Na] + [Cl] at macula densa linked with control of renal arterial resistance
Control of tubular resorption = control of distal solute delivery
Afferent arteriole resistance
Efferent arteriolar feedback (hormonal)
What is released from the granular cells of the kidney?
Renin
What is released from the juxtaglomerular cells of the kidney?
Renin
Where are the macula densa cells found in the kidney?
Next to the glomerulus in the DCT
What is the process of tubuloglomerular feedback if GFR increases?
Inc GFR -> Inc NaCl delivery to DCT lumen -> Inc in NKCC2 transport of MD cells -> Inc intracellular [NaCl] -> ATP released extracellularly -> ADP -> AMP -> Adenosine -> binds to A1 receptor on extraglomerular mesangial cells in AA -> Gq receptor -> PLC -> DAG and IP3 -> Calcium released from SER in mesangial cells -> gap junctions -> smooth muscle cells -> smooth muscle contraction -> decreased lumen of AA -> decreased pressure distal -> dec GFR
What causes renin to be released from the kidney?
Low blood pressure hence reduced renal blood flow - detected by baroreceptors in JGA
Decreased NaCl delivery from the DCT to the juxtaglomerular cells
Direct sympathetic stimulation of the JGA
What is the immediate response of a decreased in GFR?
Sensed in AA =>Prostaglandin release (PGI2 and PGE2) from the MD cells -> vasodilation -> inc blood flow -> GFR inc
Sensed in EA => Angiotensin 2 + Norepinephrine released
Are there and if so where are baro-receptors in the kidneys?
Yes
Found in the Juxtaglomerular apparatus
What chemical neurotransmitter acts to cause sympathetic stimulation of the JGA?
Dopamine
What does renin do?
Angiotensiongen -> Ang1
What is the action of angiotensin converting enzyme?
Convert ANG1 -> ANG2
What are the effects of Angiotensin 2?
1 - Increase sympathetic activity
2 - Increase Na,Cl,K reabsorption from the DCT -> H2O retention
3 - Stimulate pituitary to secrete ADH -> H2O reabsorption increases
4 - Stimulate adrenals -> aldosterone secretion -> increase Na,Cl,K reabsorption
5 - Arteriolar vascoconstriction
What are the 3 layers of the adrenal cortex gland?
Zona glomerulosa
Zona fasciculata
Zona reticularis
From which part of the kidney is aldosterone released from?
Cortex
What are the effects of aldosterone?
1 - Upregulate Na/K pump on basolateral membrane of DCT
2 - Upregulates Na channels on CD (and colon)
3 - Stimulates secretion of K into tubule
4 - Stimulates Na and H2O reabsorption in GI, Saliva, Sweat glands
5 - Stimulates H+ secretion in CD
6 - Upregulats Na/Cl cotransporter in DCT
How does glucose get reabsorbed in the kidneys?
SGLUT symporter
Na/K sets up gradient for Na to flow down into the cell along with glucose on the apical membrane
What is the pressure-natriuresis curve?
As MAP inc the amount of Na excretion when arterial pressure to the kidneys rises would also increase to compensate.
If HTN then the amount of sodium excreted would want to remain the same as if the BP was normal in order to maintain normal blood volume. Therefore if the sodium levels rise then the BP would have to accommodate by also increasing to remove the excess sodium but this would occur at a higher BP than normal
What could be a renal cause of HTN seen in a CT angiogram of the kidneys?
Renal arterial stenosis
What sodium transporters are found in the Proximal tubule?
Na-H antiporter NaHCO3 - cotransporter Na/Glucose symporter Na/AA - cotransporter Na-Pi
What sodium transporters are found in the loop of Henle?
NaKCC (symporter)
What sodium transporters are found in the early DT?
NaCl - symporter
What sodium transporters are found in the late DT and CD?
ENaC (Epithelial Na Channels)
What is the relationship between glucose filtration, reabsorption and excretion to the plasma glucose concentration?
As plasma glucose concentration rises so the the amount of glucose filtered out of the ultra filtrate in the kidneys. This occurs up to a threshold limit of approximately 300mg/100ml or 11mmol/litre.
Above 11mmol/litre the amount reabsorbed tails off and the amount excreted increases
How does amiloride affect renal function?
ENaC inhibitor in DCT
Blocks Na/H+ anti porter in PCT
What ions are transported through the PCT 2nd and 3rd sections?
Na/K sets up Na conc gradient
Na/H anti-porter
Anion/Cl anti porter with chloride entering the cell
In the PCT what is the driving force of reabsorption?
Osmotic gradient established by solute absorption
Hydrostatic force in interstitium
Increased Oncotic force in peritubular capillary
What occurs in the descending limb of the Loop of Henle in terms of solute/ water movement?
Water is reabsorbed by paracellular and transcellular routes
What type of transport is Na moving through in the thin ascending limb of LoH?
Passive movement as the water leaving has created a gradient
What transport occurs in the thick ascending limb of LoH?
-NKCC2 channel - all reabsorbed into the cell -> blood
Na/K channel sets up some of the driving force
-K/Cl channel allows them to move into the blood
-K leaves the apical membrane down conc gradient into the lumen through the ROMK channel
What channel do potassium sparing diuretics effect?
ROMK channels on apical renal tubule surface
What is the DCT permeable to?
Early DCT - not water permeable, Na reabsorption occurs
Late DCT - water permeability is variable depending on ADH
How is Na reuptaken by the DCT?
Hypo-osmotic fluid enters DCT
Active transport of Na by NCCT (Na/Cl co-transporter) and ENaC
Water permeability is low
DCT 1 - NaCl enters across apical membrane + Na/K sets up gradient, K/Cl leaves together on the basolateral membrane
What channel is sensitive to thiazide diuretics?
NCCT on the apical membrane
In the late DCT the movement of Na through ENaC is not electroneutral, what ion does it allow paracellular transport with?
Chloride
How is calcium reabsorbed through the kidney?
In the DCT
Apical Ca transport
Ca bound to calbindin which shuttles calcium to the basolateral aspect of the DCT
Transported out by NCX and Ca ATPase
What 2 types of cells are found in the cortical collecting ducts?
Principal cells and Intercalated cells
What is the function of principal cells?
Reabsorption of Na via ENaC on apical membrane
Na/K ATPase driving force of gradient
ROMK allows K to leave the cell on apical surface
Cl uptakes via paracellular route
Variable H2O uptake through AQP channels dependent on ADH
What is the function of intercalated cells?
3 types of intercalated cells A-IC, B-IC and Type B
Type B-IC Secrete HCO3
Type A-IC Secrete H+
In cortical and outer medullary CD:
Type A-IC = express H+ ATPase and H/K ATPase at the apical membrane
Express Cl/HCO3 exchanger at basolateral membrane
Where in the kidneys is most of the water re-absorbed?
Proximal tubule and descending thin limb of LoH
Where in the kidneys is most of the sodium re-absorbed?
PT -> Ascending thin and thick limb of LoH
What is normal plasma osmolality?
280-300 mOsm/Kg
How many of the nephrons are cortical and how many are juxtamedullary?
85-90% Cortical
10-15% Juxtamedullary
Which of the nephron types are responsible for making concentrated urine?
Juxtamedullary
What is the vertical osmolality gradient and how is it formed?
Large vertical osmotic gradient established in the interstitial fluid of the medulla
Isotonic at corticomedullary border 300mOsm/Kg
Hyperosmotic at medullary interstitium 1200 mOsm/Kg
Active NaCl transport in thick ascending limb - recycling of urea (effective osmole)
Ascending limb LoH -> NaCl active transport into interstitium
Descending limb LoH -> H2O passive moves out
As more NaCl is transported out more H2O moves out passively behind it.
Concentrates the filtrate even more
How is urea removed from the PT?
Urea/Na co-transporter
Urea passively moves into blood on basolateral side
Na/K ATPase maintains Na gradient
What is urea recycling in the kidneys?
Urea reabsorbed from medullary CD
Under influence of ADH fractional excretion of urea decreased and urea re-cycling increases i.e. more ADH = more urea re-absorbed through AQP1 channels
How do the vasa recta in the kidneys help the counter current?
Concentration gradient produced by the loop of Henle acting as a counter current, opposite direction to the flow of the ultrafiltrate and direction of travel in the LoH
Slow flow prevents wash out and allows equilibrium at each stratification level
Where are osmoreceptors found?
Hypothalamus
What are the 2 responses for high plasma osmolarity?
1 - ADH release to increase AQP and water reabsorption
2 - Changing behaviour to drink more water - thirst
How does BP alter response to changes in osmolarity?
At lower plasma osmolality e.g. 260 mOsm/Kg a decrease in volume/ BP will have a greater impact on the release of ADH than if there was a higher plasma osmolality e.g. 300 mOsm/Kg.
Volume is more important than osmolality if volume crashes
What is the condition where too little ADH is produced?
Diabetes insipidus
What happens in diabetes insipidus?
Too little ADH produced
Damage to hypothalamus or pituitary gland
Water is inadequately reabsorbed from CD therefore large amount of urine produced
What is the condition when the kidneys are insensitive to ADH?
Nephrogenic diabetes insipidus
What happens in nephrogenic diabetes insipidus?
Acquired insensitivity of kidney to ADH
Water is inadequately reabsorbed from CD -> large volume urine produced
Tx - ADH injections/ spray
What is the condition called when there is too much ADH produced?
Syndrome of inappropriate ADH
SIADH
What happens in SIADH?
Excessive release of ADH from posterior pituitary or other source
Dilutional hyponatraemia - too much fluid not enough sodium
What blood test results would be seen in SIADH in terms of serum osmolality, urine osmolality, urine sodium?
SIADH - excess ADH produced therefore water reabsorbed in larger amounts
Serum osmolarity - low
Urine osmolarity - high
Urine sodium - high
How do you treat SIADH?
Fluid restriction Low Na diet Hypertonic saline Diuretics If drug induced change the drug
What are common symptoms of hyponatraemia?
Aggitation Nausea Focal neurology Coma Seizures
Name 4 causes of true Na loss
D+V
Diuretics/ Renal failure
Peritonitis
Burns/ CF
If you correct hyponatraemia too quickly what is the condition that results called?
Central pontine myelinolysis
Osmotic demyelination syndrome
Fluid shifting into CNS which normally compensates well
How do you calculate osmolarity?
2Na + Glucose + Urea all in mmol/L
What causes hypovolaemic hyponatraemia?
Non-renal losses:
GI losses - D+V, Fistulas
Excessive sweating
Third spacing of fluids- ascites, peritonitis, burns
Cerebral salt-wasting syndrome: traumatic brain injury/ intracranial surgery etc can lead to sodium losses
If urine sodium is low but hypovolaemic what could be the cause?
GI/Skin losses
If urine sodium is low but hypervolaemic what could be the diagnosis?
CCF
Nephrotic syndrome
Liver failure
If urine sodium is high + hypovolaemic what could be the diagnosis?
Renal loss
If urine sodium is high + hypervolaemic what could be the diagnosis?
Renal failure
If urine sodium is high + euvolaemic what could be the diagnosis?
SIADH
What are potential side effects of hyper or hypokalaemia?
Nerve dysfunction and cardiac arrest
How long does insulin roughly reduce potassium for?
6 hours
Why is most of the potassium inside the cell?
Na/K ATPase
What are the ECG findings in hypokalaemia?
Depressed ST wave
Diphasic T wave
Prominent U wave
What are the ECG findings in hyperkalaemia?
Tall tented T waves
Long PR interval
Wide QRS duration
> 9mEq/L - Absent P waves + Sinusoidal wave
What are symptoms of hypokalaemia?
AF Muscle weakness Muscle cramps Constipation <2.5= cardiac conduction abnormalities, cardiac arrest
Where is most of the potassium excreted from?
Renally
Which part of the nephron is potassium reabsorbed from?
PCT - 67%
Ascending thick limb LoH - NKCC2 channel - 20-25%
DCT - K+ and other cations
How does aldosterone affect potassium?
Stimulates potassium secretion into the lumen therefore antagonists -> hyperkalaemia
Which part of the nephron does aldosterone affect?
DCT/ CD
What drug affects potassium reabsorption in the PCT?
Acetazolamide
Where do thiazide diuretics work in the nephron?
DCT
Na/Cl channels
What problems can cause poor renal potassium excretion?
AKI, CKD
Potassium sparing diuretics
ACE-I, ARBS
Aldosterone deficiency
What problems can cause increased potassium release from cells?
Acidosis
Cellular breakdown - ischaemia, toxins, chemo, rhabdomyolysis
What methods can cause increased potassium to be administered?
Potassium in IV fluid
Blood transfusions
What are the immediate treatments for hyperkalaemia?
Insulin
Salbutamol
Calcium - stabilises cardiac membrane potential
What are the longer term treatments for hyperkalaemia?
Low potassium diet Calcium resonium binds GI K+ Stop meds Furosemide - enhances K+ loss Dialysis
What are potential causes of hypokalaemia?
Insulin, alkalosis, beta-2 agonists
Extra renal cause - diarrhoea, laxatives
Decreased intake
Renal losses- diuretics, renal tubular acidosis, DKA
What 3 things mainly increase Na/K ATPase activity?
[K+] in plasma
Insulin
Noradrenaline on B2-adrenoceptors
What drug inhibits Na/K ATPase to an extent that causes hyperkalaemia?
Digoxin (Digitalis)
What is Liddle’s syndrome?
ENaC channels increase therefore more Sodium is reabsorbed and less potassium is reabsorbed
By what 4 methods causes hypokalaemia with increased urine loss?
- inc aldosterone - volume depletion, primary hyperaldosteronism, secondary hyperaldosteronism
- Inc urine flow
- Renal tubular acidosis
- Magnesium deficiency
How much glucose is generally required in a hospitalised non-diabetic patient to avoid starvation ketosis?
50-100grams
How much sodium, potassium and chloride is required per day as maintenance (orally/ IV)?
1mmol/Kg/day
How much water is generally required per day?
30ml/kg/day
What IV fluid is given to a patient on variable rate insulin?
Dextrose and potassium bag
0.45% saline with 5% glucose and 0.15% potassium chloride
What nerves supply the detrusor muscle?
Parasympathetic S2,3,4 (pelvic nerves)
What nerve roots supply the external urethral sphincter?
Pudendal nerve - S2,3,4
What side effect does having a weakened pelvic floor in women lead to?
Urinary incontinence
What are the 2 phases of normal bladder function?
Filling phase - storage. Receptive relaxation, sensation of bladder filling, no detrusor contraction
Voiding phase - voluntary initiation, complete emptying
What does a lower motor neurone lesion cause in terms of urinary continence/ incontinence?
Low detrusor pressure -> large residual urine +/- overflow incontinence
What does a upper motor neurone lesion cause in terms of urinary continence/ incontinence?
Dilated ureters, thickened detrusor muscle -> High pressure detrusor contractions -> Poor coordination with external sphincters -> detrusor sphincter dyssynergia
What are the categories of Lower Urinary Tract Symptoms?
Storage
Voiding
Post-micturition
What are Storage LUTS?
Increased frequency
Incontinence
Nocturia
Urgency
What are voiding LUTS?
Slow stream Splitting or spraying Intermittency Hesitancy Straining Terminal dribble
What are post-micturition LUTS?
Post-micturition dribble
Feeling of incomplete emptying
Define urinary incontinence
Complaint of any involuntary leakage of urine
What are the 4 types of incontinence?
Stress urinary incontinence
Urgency urinary incontinence
Mixed urinary incontinence
Overflow incontinence
Define stress incontinence?
Complaint of involuntary leakage on effort or exertion, or on sneezing or coughing
Define urgency urinary incontinence
Leakage or urine accompanied by or immediately preceded by urgency
Define mixed urinary incontinence
involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing
Define overflow incontinence
chronic painless retention e.g. lower motor neurone causes
What are risk factors for urinary incontinence?
Pregnancy/ childbirth Pelvic surgery Pelvic prolapse Race, FMHx, Anatomical abnormalities, neurological abnormalities Co-morbidities, obesity, age Inc intra-abdo pressure Cognitive impairment UTI, drug menopause
What examinations would be done if a patient complains of urinary incontinence?
BMI
Abdo exam to exclude palpable bladder
Digital rectal exam - prostate in males specifically
Females - external genitalia stress test - cough and see if collection, vaginal exam
What are investigations done if a patient complains of urinary incontinence?
Urine dipstick - UTI, haematuria, proteinuria, glucosuria
Urodynamics - frquency-volume chart, bladder diary, post-micturition residual volume
Cystoscopy
What are conservative managements of urinary incontinence?
Modify fluid intake weight loss stop smoking decreased caffeine intake avoid constipation timed voiding - fixed schedule - normally for 4 hourly to keep healthy
How could you contain the incontinence?
Indwelling catheter
Sheath device - condom attached to catheter tubing and bag
Incontinence pads
How do you manage stress incontinence?
1 - Pelvic floor muscle training - 8 contractions/ day TDS -
3/12 duration of treatment
2 - Duloxetine - SNRI/ SSRI - inc activity of striatal muscle of EUS
3 - Surgery - Females= retropubic suspension procedure/ intramural bulking. Males = artificial urinary sphincter, male sling
What is a retropubic suspension procedure?
Tightening up of the levator ani muscle with a sling that goes around the ureter and up the abdominal wall
How do intramural bulking agents work?
Improve ability of urethra to resist abdo pressure
Inject - fat, silicone, collagen into the urethra
How does bladder training work?
void every hour - not in between, wait
Intervals of no voiding increased by 30mins-1hour until interval of 2-3hours reached
What are pharmacological treatment options of urgency urinary incontinence?
Anticholinergic Act on M2,M3 receptors - Oxybutynin, solifenacin
B3- adrenoceptor agonist - Mirabegron
Intravesical injection of Botox - neurotoxin - inhibits release of ACh - flaccid paralysis
Define enuresis
Bedwetting = involuntary wetting during sleep at least 2x/ week in children aged >5 years with no CNS defects
What is primary enuresis?
Never achieving sustained continence at night
What is secondary enuresis?
Enuresis restarted having been dry at night for 6+months
How do you manage enuresis in children?
Primary enuresis - primary care, reassurance, alarms with positive reward system, desmopressin
Secondary enuresis - treat underlying cause, e.g. UTI, constipation, diabetes, psychological problems, family problems etc
What are two main types of nephron pathologies?
Nephritis - Blockage - renal failure therefore dec. GFR
Nephrotic - Leakage - proteinuria, haematuria
What are common primary causes of nephrotic syndrome?
Podocyte/ sub epithelial damage/ glomerular basement membrane
Primary causes: Minimal change glomerulonephritis, focal segmental glomerulosclerosis, membranous glomerulonephritis
What are common secondary causes of nephrotic syndrome?
Diabetes mellitus
Connective tissue diseases e.g. SLE
What is minimal change glomerulonephritis?
Childhood or adolescent Due to unknown circulating factor damaging podocytes - immunologic origin as responds to steroids - but no immune complex deposition Heavy proteinuria or nephrotic syndrome Responds to steroids May recur Usually no progression to renal failure
What is focal segmental glomerulosclerosis (FSGS)?
Similar to Minimal change glomerulonephritis
Nephrotic
Less responsive to steroids
Glomerulosclerosis
Circulating factor damages podocytes - even in transplant patients they get FSGS in that kidney
Progression to renal failure
What is membranous glomerulonephritis?
Commonest cause of primary nephrotic syndrome in adults
Rules of thirds on recovery- 1/3 recover fully, 1/3 recover partially, 1/3 never recover and progress to renal failure
Immune complex deposits cause damage
May be secondary - e.g. associated with lymphoma
How do sub epithelial deposits in the glomerulus cause problems?
1 - Immune complexes can’t get through the podocytes
2 - Antigen on the podocytes attracted by antibodies that are against these antigens causing immune reaction -> damage
What could haematuria be a sign of in terms of renal deposition pathology?
IgA nephropathy
Commonly after URTI
Thin glomerular basement membrane
How does good pasture’s syndrome present and how is it treated?
Nephritic syndrome
Haemoptysis, cough,
Anti-GBM disease
Tx - steroids, plasmapheresis
What is IgA nephropathy?
Glomerulonephritis Visible/ invisible haematuria Relationship with mucosal infection hence IgA \+/- proteinuria -> renal failure
What is vasculitis?
Group of systemic disorders - inflammation of blood vessels including glomeruli
No immune complex deposition
Associated with Anti Neutrophil Cytoplasmic Antibody (ANCA)
Nephritic presentation - rapidly progressing GN
Treatable - immunosuppression
What is the difference between nephrotic and nephritic in terms of area affected?
Nephritic - Inflammation disrupting GBM
Nephrotic - Podocyte damage leading to glomerular charge - barrier disruption
What is the nephrotic triad?
Proteinuria >3.5g/24hours
Hypoalbuminaemia
Oedema
(accompanied by hypercholesterolaemia)
What secondary causes are there of nephrotic syndrome?
Diabetes
SLE
Amyloid
How do you manage nephrotic syndrome?
Oedema - fluid/salt restrict + loop diuretics
ACE-I = anti-proteinuric
Hypercholesterolaemia = statin
Tx underlying condition
What is the triad of nephritic syndrome?
Haematuria
Reduction in GFR
HTN
(some proteinuria, rapid onset)
How do you manage nephritic syndrome?
BP control - ACE-I/ ARB + salt restriction
Oedema - loop diuretics + fluid restrict
Disease specific - steroids, immunosuppressants
CVS risk - statins, modifiable risk factors
Dialysis - short term if required
What happens to the GBM in diabetes?
It gets thicker with mesangial expansion
This decreases the ability to filter effectively
What are the pathological changes in diabetic nephropathy?
1 - hyper filtration/ capillary HTN 2 - GBM thickening + lipoprotein deposition 3 - Mesangial expansion 4 - Podocyte injury 5 - Glomerulosclerosis/ arteriosclerosis
How is glucose re-uptaken in the renal cells?
Apical membrane = SGLT2 transporter - symporter with Na+
Basolateral side = passive facilitated through GLUT-2 transporters
Why in diabetes is there hyper filtration in the glomerulus?
Inc glucose delivery to nephron -> more glucose reabsorbed + Na+ -> less Na/Cl delivery to macula densa cells -> release of renin -> inc BP -> HTN
What is the relationship between proteinuria and GFR in diabetes?
Initially -> Increased GFR -> very slight inc proteinuria
5-10 years = dec GFR -> increasing proteinuria
20 year mark = GFR < proteinuria (damage is done and is enough to now cause a rapid decline in GFR)
What are the 5 stages of diabetic nephropathy?
1 - hyper filtration and hypertrophy 2 - latent stage 3 - microalbuminuria 4 - overt proteinuria 5 - ESRD
Describe what is seen in microalbuminuria due to diabetes
GBM thickening Mesangial expansion Albuminuria 30-300mg/day Potentially still reversible here
Describe what is seen in overt proteinuria due to diabetes
GFR normal initially -> drops in linear fashion
Mesangial expansion / sclerosis - reduced surface area for filtration
Proteinuria >30mg/mmol
Worsening systemic HTN
Microvascular changes - tissue ischaemia
ESRD - 3-7years reached
Irreversible damage
How do you manage microalbuminuria and proteinuria?
Inhibit RAAS Tight BP control Statins CV risk management Moderate protein intake Tight glucose control
How would SGLUT2 inhibitors help with diabetic nephropathy?
Blocking Na/Glucose reabsorption -> more sodium delivery to macula densa -> reduced feedback to increase BP -> normalised GFR -> reduced hyperfiltration
What is classed as an Upper UTI and a Lower UTI?
Upper UTI Bladder and above
Lower UTI Bladder and below
What is the pathophysiology of a UTI?
Urinary tract normally sterile and resistant to bacterial colonisation
Ascending colonisation of bacteria from urethra
What are the major defences for getting a UTI?
Emptying of bladder (micturition), vescio-urethral valves, immunological factors (IgA), mucosal barriers, urine acidity
What is the term used to describe a bladder infection and a kidney infection?
Cystitis
Pyelonephritis
What age ranges do UTIs peak?
Infants and pre-school <5 years
20-25 Honeymoon cystitis + pyelitis of pregnancy
>65 years - prostatism
What are 6 risk factors for UTI and why?
Female - short UTI
Neurological condition - MS, strokes
Pregnancy - enlarged uterus, hormone effects
Abnormal renal tract - vesicle-ureteric reflux in children, indwelling catheter
Impaired host defence - DM, immunosuppression
What is the most common bacterium causing a UTI
Coliforms (found in colon)
E. coli
Gram negative
Then: Proteus -> Enterococci
Why is E. coli so good at causing UTIs?
Flagellar, pili - help move and stick
Capsule polysaccharide - colonisation
Haemolysin, toxins - damage host defence and membranes
What are 7 symptoms and signs of cystitis?
Dysuria Cloudy urine Nocturia/ increased frequency Urgency Suprapubic tenderness Haematuria Pyrexia
What are 3 signs and symptoms of pyelonephritis (excluding cystitis signs and symptoms)?
High fever +/- rigors
Loin pain and tenderness
N+V
+/- symptoms of cystitis
Define uncomplicated UTI
Infection by a usual organism in a patient with a normal urinary tract and normal urinary function
Define complicated UTI
≥1 factor that predisposes to persistent infection, recurrent infection or treatment failure:
- Abnormal urinary tract
- Virulent organism
- Impaired host defence
- Impaired renal function
What investigations would be done for a patient presenting with a complicated UTI?
Urine culture
MSU - mid-stream urine collection
Urine dipstick - leucocyte esterase, nitrites, blood, pH, protein
Why are urine dipsticks not useful in >65yrs?
Asymptomatic infection is common in upto half of the population
What is sterile pyuria?
Raised white cells in the urine but no growth of bacteria
What could cause sterile pyuria?
Prior antibiotics Urethritis (chlamydia/ gonococci) Vaginal infection/ inflammation TB Appendicitis
What is asymptomatic bacteriuria?
Significant levels of bacteria in urine with UTI symptoms
High prevalence in elderly, indwelling catheters
Screened for and treated only in pregnancy
What is the treatment of UTIs?
Increase fluid intake Regular analgesia Address underlying disorders 3 day course for uncomplicated UTI 5-7 day course for complicated lower UTI
What medications can be used to treat simple cystitis?
Nitrofurantoin Trimethoprim Pivmecillinam Fosfomycin Treatment duration = 3 days
What medications can be used to treat complicated lower UTI?
Nitrofurantoin Trimethoprim Pivmecillinam Fosfomycin Cefalexin Treatment duration = 5-7 day course
What medications would be used to treat pyelonephritis?
IV ABx - co-amoxiclav, ciprofloxacin, gentamicin
Treatment duration = 7-10days
When would UTI prophylaxis be used?
No treatable underlying condition despite behavioural and personal hygiene measures
If ≥3 UTI episodes/ year
What causes urolithiasis?
Metabolic - secondary to hypercalcuria UTI - proteus, pseudomonas, klebsiella Diet - high in salt, obesity Medication - furosemide Genetic - primary hyperoxaluria, cystinuria
How are urate stones treated?
Alkanisation
Define CKD
Progressive loss of renal function over a period of months or years
Symptoms of worsening kidney function are unspecific
Define AKI
A abrupt decrease in renal function within 48hours
If baseline serum Cr = ≥1.5 times baseline
OR
Urine volume <0.5ml/kg/hour for 6 hours
OR
Inc in serum Cr >26.5micromol/L within 48hours
What are the CKD stages and renal functions?
CKD 1: eGFR >90 with proteinuria/haematuria
CKD 2: eGFR >60 with proteinuria/ haematuria
CKD 3: eGFR 30-60
CKD 4: eGFR 15-30
CKD 5: eGFR <15
End stage renal failure
What are 6 causes of CKD?
20% diabetes nephropathy HTN Glomerulonephritis UTI Polycystic kidney disease Renal vascular disease
What are the 3 stages of AKI?
Stage 1: Serum creatinine 1.5-1.9x baseline OR Urine output <0.5ml/kg/hour for 6 hours Stage 2: Serum creatinine 2.0-2.9x baseline OR Urine output <0.5ml/kg/hour for ≥12 hours Stage 3: Serum creatinine 3.0x baseline OR Urine output <0.3ml/kg/hour for ≥24hours or Anuria ≥12hours
What are AKI causes split up into?
Pre-renal
Renal
Post-renal
What are renal causes of AKI?
Drugs: antibiotics, NSAIDs, ACE-I Sepsis Rhabomyolysis Myeloma Tubulointersitital disease GN
What are pre-renal causes of Aki?
Renal artery stenosis
Hypoperfusion: Septic shock, hypovolaemic shock, cardiogenic shock
How do you treat AKI?
Fluid replacement
Dialysis
Electrolyte replacement/ management
What is adult polycystic kidney disease?
Autosomal dominant condition
Mutation in polycystic kidney disease gene
Cysts grow with age - present in adulthood
Diagnosed with ultrasound
In adult polycystic kidney disease what are secondary complications?
Pain Bleeding into cyst Infection Renal stones HTN
How do you treat adult polycystic kidney disease?
Inhibit RAAS
Diet - drink plenty of fluid, low salt, normal protein
Tolvaptan
Somatostatin analogues
What blood tests would be helpful in CKD management?
U+Es, Bone biochemistry, LFT, FBC, CRP
+/- iron levels (ferritin, iron, reticulocyte Hb)
+/- PTH
What blood tests would be helpful in diagnosing the cause of CKD?
Auto-antibody screen (auto-immune)
Complement levels (auto-immune)
Anti-neutrophil cytoplasmic antibody (vasculitis)
Serum immunoglobulin screen (myeloma)
Protein electrophoresis and serum free light chain measurement (myeloma)
How do you manage CKD?
Modifiable risk factors
Control DM, HTN, Proteinuria (with ACE-I), Lipids
How does CKD effect water/ salt handling by the kidneys?
Lose ability to maximally dilute and concentrate urine
Small glomerular filtrate but same solute load causes osmotic diuresis
Low volume of filtrate reduces maximum ability to excrete urine therefore maximum urine volume is much smaller
How do you treat acidosis in CKD?
Sodium bicarbonate capsules
How do you treat anaemia in CKD?
Hb low -> Iron levels first -> replace if low -> Hb recheck -> if low start Epo
How do you manage CKD- bone mineral density?
Reduce phosphate intake
Phosphate binders
Vit D
In the prostate where are most cancers found?
Peripheral zone
What are the main risk factors for prostate cancers?
Older age
FMHx - 4x risk. BRCA2 gene mutation
Ethnicity - Black>white>asian
What are some issues with PSA screening?
Over diagnosis -> over treatment
Quality of life would be reduced
Cost-effectiveness
Apart from prostate cancer what are reasons for a raised PSA?
Urinary Infection
Prostate inflammation
Large prostate
Urinary retention
What are common presentations of prostate cancer?
Urinary symptoms Bone pain PSA checked -> biopsied DRE for another reason Incidental finding at transurethral resection of prostate for urinary retention/ urinary symptoms
What is the tumour staging of the prostate?
T1 - local in peripheral zone
T2 - local in peripheral zone but much larger than T1 and also starting to affect the outer margins of the prostate
T3 - locally advanced -> very nodular and also spreading to local sites i.e. seminal vesicles etc.
T4 - Advanced - spread to more than the urinary system e.g. bone, colon and having a mass effect
What is the scoring system for prostate cancers?
Gleason score
Score from 1-5 given to the type of cells in the largest area
Score from 1-5 given to the type of cells in the second largest area
Scores tallied up and final score is the Gleason score
1 - healthier tissue 5 - most abnormal tissue
Score of ≥7 means risk of cancer likely
What is the treatment for a locally advanced prostate cancer?
Surveillance
Hormones
Hormones + radiotherapy
What is the treatment for a local prostate cancer?
Surveillance
Robotic radial prostatectomy
Radiotherapy - external beam, brachytherapy
Where is a common place for prostate cancers to metastasise to and what type of met are they?
Bone
Bone mets are sclerotic
What treatments are for metastatic prostate cancer?
Hormones (+/- chemotherapy):
Surgical castration
Medical castration - decrease testosterone enough to castration levels. -> LHRH agonists.
Palliation
Where do TCC and RCC originate from?
TCC - Kidney + Ureter + Bladder + Urethra
RCC - Kidney parenchyma only
How does RCC present?
Haematuria
Incidental finding on imaging - US/ CT
Rare - palpable mass
If advanced - Large varicocele may be present, PE, tumour embolus, loss of weight/ appetite, hyper calcaemia
How does TCC present?
Haematuria
Incidental finding on imaging
If advanced - loss of weight, appetite
DVT
Lymphoedema
What are the 3 classes of haematuria?
Visible
Dipstick
Microscopic
What are differential diagnosis for haematuria?
Cancer - RCC, TCC, metastatic prostate carcinoma
Other - stones, infection, inflammation, BPH
Nephrological - glomerular cause
What are risk factors for developing RCC?
Smoking
Obesity
Dialysis
What are the 3 ways that RCC spreads?
Perinephric spread
Lymph node mets
IVC spread to right atrium
How do you treat localised RCC?
Surveillance
Excision - radical/ partial
Ablation - cryoablation, radiofrequency
How do you treat metastatic RCC?
Palliative - Tyrosine kinase inhibitors
What is the most common type of bladder cancer?
TCC - 90%
What are risk factors for bladder TCC?
Smoking Occupational exposure (20yr latent period) - rubber or plastic manufacture (arylamines), handling of carbon, crude oil, combustion, smelting (polyaromatic carbons), Painters, mechanics, printers, hairdressers
What are initial treatments of bladder TCC?
TURBT- TransUrethral Resection of Bladder Tumour
Local instillation of mitomycin C - local effects
How is bladder TCC staged?
75%
Ta - into the bladder from the epithelium
T1 - epithelium + sub epithelial connective tissue
5%
Tis - Epithelium confined - carcinoma insitu
T2-4 = muscle-invasive
What are risk factors for upper urinary tract TCC?
Smoking
Phenacetin abuse
Balkan’s nephropathy
How do you investigate using imaging for upper urinary tract TCC?
Ultrasound - hydronephrosis
CT urogram - filling defect, ureteric stricture
Retrograde pyelogram
Ureteroscopy - biopsy, washings for cytology
What are standard treatments for upper urinary tract TCC?
Nephro-ureterectomy
How do you treat metastatic TCC?
Systemic chemotherapy - cisplatin based treatment
Biologics - programmed cell death receptor 1 drugs
What can cause ureteric strictures?
Intraluminal - stones, sloughed off papilla, clots
Intramural - PUJ obstruction, TCC,
Benign - TB, surgery
What can cause ureteric obstruction?
Extraluminal - retroperitoneal malignancy
Direct obstruction by a tumour - bladder cancer (obstruction at vesicoureteric junction), locally advanced prostate cancer
Retroperitoneal fibrosis
What could cause an acute ureteric obstruction?
Calculus - stone
Blood clots
Sloughed papilla
Superadded infection-> pyonephritis or infected obstructed system
What are problems with obstructive uropathy?
Renal impairment- bilateral ureteric obstruction, unilateral ureteric obstruction (solitary kidney), high pressure chronic retention
Post-renal AKI
Hyperkalaemia
What is pyonephritis?
Infected, obstructed kidney - urological emergency
Failure to decompress - sepsis or permanent loss of renal function
What are two causes of non-obstructive hydronephrosis?
Vesico-ureteric reflux
Pregnancy
What imaging technique will be done to diagnose a upper urinary tract obstruction?
Diuretic renography with MAG3 = functional test
What are options for treatment of an upper tract drainage?
JJ stent
Good for intraluminal not good for extraluminal
The JJ part - ring part - keeps it in place
Nephrostomy
What is a clinical presentation of PUJ obstruction?
Loin pain
Worse after heavy fluid intake or alcohol
Definitive treatment is a pyeloplasty
What are potential causes of retroperitoneal fibrosis
Idiopathic Malignant Auto-immune Drugs AAA
What are problems of infravesical obstruction?
Acute urinary retention - painful
Chronic urinary retention - high and low pressure - painless
In urinary retention, what type of pain is felt and are patients still voiding?
Acute - painful, inability to void
Chronic - painless, may still be voiding
What are causes of urinary retention?
Men: BPH, Prostate cancer
Both men and women: UTI, constipation, neurological dysfunction, recent surgery, drugs, urethral strictures, pelvic mass
How do you treat acute urinary retention?
Catheterise Abdo, rectal, genital exam Urine dip Tx constipation Alpha blocker TWOC TURP in Men
What are problems with high and low pressure chronic urinary retention?
High - hydronephrosis - abnormal U+E’s
Low - no hydronephrosis - normal renal function
How do you treat chronic urinary retention?
Catheterise
Urine dip
Bloods
Monitor for post-obstructive diuresis
What is post-obstructive diuresis?
Physiological off-loading of accumulated salt and water during chronic retention
Excess/severe unloading - dehydration and electrolyte imbalane
If the bladder is filling what is the neuronal reflex arc to store urine?
Bladder stretch -> detection by sensory afferent -> signals sent to CNS ->
(1) excitatory onto sympathetic pre-ganglionic neurone -> sympathetic postganglionic -> bladder wall (negatively stimulated) + EUS (positively stimulated)
(2) positive signal to parasympathetic neurone in CNS -> overall inhibitory signals to preganglionic parasympathetic neurone -> no signals sent to bladder to contract
If the bladder is full what is the control arc of micturition?
Active conscious decision made to urinate -> M center in PONS ->
(1) Inhibitory signal to L (urination) centre in Pons -> (a) Less excitatory signal sent to pudendal nerve -> less innervation of EUS -> relaxation and increasing lumen of urethra. (b) inhibitory signal sent to sympathetic pre-ganglionic neurone -> less signals sent through postganglionic sympathetic neurone -> less inhibition of bladder to contract and less activation of the IUS to relax
(2) Excitatory signal to preganglionic parasympathetic nerve in CNS -> bladder wall -> postganglionic neurone bladder wall -> release of ACh on M3 receptors - bladder contraction
Sensory afferent in bladder wall -> preganglionic parasympathetic nerve in CNS -> bladder wall -> postganglionic neurone bladder wall -> release of ACh on M3 receptors -> bladder contraction
If there is a spinal cord injury at the base of the spine in the L3-5 region what is the potential problem seen in bladder control and micturition?
Less inhibitory signals sent to the preganglionic parasympathetic nerve to the bladder. Small stretch will cause the parasympathetic to be over activated -> more ACh release onto bladder wall -> increase activity and contraction of bladder -> spinal micturition reflex over active
If there is a spinal cord injury at the level of the sacral level S2-S4 (caudal equina) what could be the potential problem?
The sensory afferents to the parasympathetic nerve is not going to be received as the nerve is damaged -> no voiding via PNS. Excessive stretch signals sent to M centre -> sympathetic signals sent down to PNS preganglionic nerve -> no signals sent as this nerve is damaged -> no voiding
