Urinary S7 (Done) Flashcards
At what stages of life are UTIs more common?
Infancy/Preschool:
Males experience a rise in prevanelnce of UTI at 0-5 yrs
Females experience the same rise from ages 0-10
Mid life:
Women in the 20s experience a rise in UTI prevalence as sexual activity increases
UTIs due to sexual activity are known as ‘Honeymoon cystitis’
Later life:
From ages 60+ both sexes experience a rise in UTI prevalence
In men this is due to prostatism and a greater rise in prevalence is seen
What are some host factors affecting UTI?
Urethral length:
Shorter urethra in women raises risk of UTI
Obstruction:
Prostatism, pregnancy, stones and tumours can all increase risk of UTI
Neurological problems:
Incomplete emptying of the bladder and residual urine can increase UTI risk
Ureteric reflex:
Reflux of urine into the ureters increases UTI risk
Ascending infection from the bladder common in children
What are the common sites of urinary tract obstruction?
For each site, what is the likely cause(s) of obstruction?
Pelvic-ureteric junction:
Caliculi (stones)
Ureters:
Caliculi, retroperitoneal fibrosis
Bladder:
Neuropathic bladder
Vesico-ureteric junction:
Caliculi
Prostate:
Benign prostatic hypertrophy
Urethra:
Stricture
What are the virulence factors that increase a bacteria’s ability to cause UTI?
Fimbriae:
To allow attachment to host epithelium
K antigen:
Permits production of polysaccharide capsule
Haemolysins:
Damage membrane and cause renal damage/inflammation
Urease:
Breaks down urea creating a favourable evirnoment for bacterial growth
What are the common pathogens in UTI?
G- bacilli (Enterobactericae/Coliforms, E. coli)
Coagulase (-) staphylococci
Other G- (E.g. Pseudomonas aeruginosa)
How can we differntiate Upper UTI and Lower UTI clinically?
UUTI Symptoms/signs:
Fever
Loin pain
Maybe dysuria and increased frequency of urination
LUTI Symptoms/signs:
Sometimes low grade fever
Dysuria
Increased frequency of urination
Urgent need to urinate (w/ Little urine produced)
Give 3 Lower UTIs and their characterisitic
Bacterial cystitis:
Frequency and dysuria often with pyuria (WBCs in urine) and haematuria
Abacterial cystitis:
As above but without significant bacteriuria
Prostatism:
Fever, dysuria, frequency with perineal and low back pain
Give 2 forms of upper UTI and their characterisitics
Acute pyelonephritis:
Symptoms of cystitis (Frequency, dysuria, pyuria, haematuria)
+ Fever and Loin pain
Chronic interstitial nephritis:
Renal impairement following chronic inflammation, infection is one of many causes
What is Covert Bacteruria?
Bacteriuria only detected by culture
Significant in children and pregnancy
What is a common complication of UTI?
Common source of G-neg bacteriaemia and subsequent septicaemia +/- shock
When is a urine sample needed to confirm clinical diagnoses of UTI?
Not needed in uncomplicated UTI (healthy women of child bearing age)
Urine culture needed for complicated UTI such as:
- Pregnant patient*
- Treatment failure for UTI*
- Reccurent infection*
- Suspected pyelonephritis*
- Complications*
- Male or Paediatric*
What near bed testing and laboratory testing is available for diagnoses of UTI?
Near bed:
Turbidity inspection
Dipstick
Labratory:
Microscopy
Urine Culture
How might a urine sample be collected?
Mid stream urine sample:
Avoids contamination of bacteria in urethra or on skin by washing them away before sample collection
Clean catch (paediatric)
Collection bag:
20% false positives
Catheter sample
Suprapubic aspiration
How should a urine sample be handled?
Kept at 4 degrees
+/- boric acid as a bacteriostatic
Describe how visual inspection of a urine sample can aid in diagnosis of UTI
Turbid urine would indicate a high bacteria/cell count, likely indicating a UTI
What is tested for by a urine dipstick?
Leucocyte esterase:
Detects WBcs
Nitrite:
Indicates presence of nitrate reducing bacteria
Haematuria
Proteinuria
What is disptick testing used for and not used for?
Used for:
Children >3
Men with mild/non-specific symptoms
Elederly women
Not used for:
Uncomplicated UTI
Men with typical/severe symptoms
Catherterised patients (false positives)
Older patients with no features of infection (asymptomatic bacteriura common)
Why is urine microscopy useful for diagnosis of UTI?
Can identify RBCs and WBCs in urine indicating UTI
Can identify contaminated samples (Epithelial cells present)
What are the diagnostic criteria for significant bacteriuria?
Why is this significant?
>10^5cfu/ml distinguishes bacteriuria/contamination from healthy patients
A single positive specimen is 80% predictive of pyelonephritis
What is the role of cultures in UTI diagnosis?
Investigation of children, males and complicated cases
High sensitivity (10^2cfu/ml detected)
Identification of specific organism:
Epidemiology of isolates
Susceptibility data
How is bacterial susceptibility to antibiotics determined?
Agar diffusion test:
Different antibiotics will create larger or smaller zones of inhibition of bacteria
Antibiotic with largest zone of inhibition is best
What are the causes of abacterial cystitis?
Low count bacteriuria
Fastidious organisms
Vaginal infection/inflammation
Sexually transmitted pathogens - urethritis
Mechanical, physical and chemical causes of inflammation
When is imaging of the urethral tract used in UTI cases?
What are the structures of interest?
UTIs in children
Also, can identify renal involvement in septic patients
Structures:
Male = Posterior urethral valve (Bladder outlet obstruction)
Female = Vesico-ureteteric valve/junction (VU reflex)
What is sterile pyuria and what might be the cause?
Pyuria present without bacteriuria
Causes:
Previous antibiotic
Urethritis
Vaginal infection/inflammation
Fastidious organisms
Non-infective inflammation (tumours, chemicals)
Urinary TB
Describe asymptomatic bacteriuria
High prevalence in older people (women)
Generally with associated pyuria (Positive dipstick)
Not associated with increase in mortality/morbidity
Leads to unneccessary antibiotic treatment
Only requires action in pregnancy and urology surgery
What are the general prinicples of UTI treatment?
Increase fluid intake
Address underlying disorders
3 day antibiotic course of uncomplicated
5 days for complicated (paeds, pregnant, male, underlying disorder)
Outline the treatment of simple cystitis
Uncomplicated infection
3 day course of trimethoprim or nitrofurantoin
Outline treatment of complicated UTI
Trimethoprim, nitrofurantoin or cephalexin for 5 days
Cultures during follow up
Outline the treatment of pyelonephritis/septicaemia
14 day antibiotic course
Use systemic agent (Co-amoxiclav, Ciprofloxacin, Gentamicin)
IV antibiotics if acutely unwell
Outline UTI prophylaxis
When is it used and what is it?
When:
3 or more infections in one year
No treatable underlying condition
What:
Trimethoprim or nitrofurantoin
Single nightly dose
All breakthrough infections documented
What is a diuretic? What are it’s effects?
**Diuretic: **A drug/substance that promotes diuresis
**Diuresis: **Increased urine formation by kidney
Effects:
Increase fractional excretion of sodium
Hence increasing excretion of Na+ and Water
Leads to a reduction in ECF volume
When are diuretics used?
In conditions where Na+ and water retention cause ECF expansion (E.g. Heart failure)
Outline the general mechanism for Na+ and water reabsorption from the nephron
Cells contain Basolateral Na+/K+ ATPase and Apical Na+ channels/transporters
Na+/K+ ATPase creates Na+ gradient across apical membrane
Luminal Na+ moves into the cell down conc gradient utilising a channel or transporter
Water moves into the cell down the osmotic gradient created by Na+ reabsorption
Each tubule segments have differnt apical channels/transporters, list which are found in each segment
PCT:
Na+/H+ antiporter
Na+ - AA/Glucose symporters
LoH:
Na+/K+/2Cl symporter
Early DCT:
Na/Cl symporter
Late DCT and CD:
ENaC
Outline the mechanism of Na+ reabsorption and related processes by principal cells
How can this process be modulated?
Basolateral Na+/K+ ATPase creates gradient across apical membrane
Na+ enters via apical ENaC
This creates a negative lumen potential, this favours K+ secretion through apical K+ channels
Aldosterone:
Increases expression of Na+/K+ ATPase, NEaC and K+ channels
Outline the classes of diuretics that work by direct action on luminal cells
Loop diuretics:
Work on LoH
Block Na+/K+/Cl symporter
Thiazide diuretics:
Act on Early DCT
Block Na/Cl cotransporter
K+ sparing diuretics:
Act on late DCT and CD
Block ENaC
How do diuretics that work via direct actions on cells exert their effects?
Secreted into the lumen in the PCT
Act on cells from within lumen
Outline how diuretics that antagonise the action of aldosterone function
Aldosterone antagonists reduce expression od Na/K-ATPase, ENaC and K+ channels on principal cells
This reduces Na+ absorption and K+ secretion
How do osmotic diuretics work?
Freely filtered at glomerulus
Not reabsorbed, remaining in lumen
Increased osmolarity of filtrate leads to reduced water and Na+ reabsorption throughout tubule
How do enzyme inhibitor diuretics typically work?
Acts on PCT
Inhibition of carbonic anhydrase:
- Enzyme that catalyses H2O + CO2 <—> HCO3- + H+
Interferes with Na+ and HCO3- reabsorption
Give the 6 groups that diuretics are classified into and give examples of each
Loop diuretics:
Furosemide
Thiazide diuretics:
Bendroflumethiazide
K+ sparing diuretics:
Amiloride
Aldosterone antagonists:
Spironolactone
Carbonic anhydrase inhibitors:
Acetazolamide
Osmotic diuretics:
Mannitol
Describe why loop diuretics are so potent
Very potent:
20-30% Na+ reabsorbed in LoH
Segments beyond have limited capacity to reabsorb large amounts of Na+ so a high % is lost
What are some uses of Loop diuretics?
Heart failure:
Reduced ECF + vaso and venodilation
Acute pulmonary oedema:
furosemide given IV for rapid action
Fluid retention and oedema in:
Nephrotic syndrome
Renal failure
Cirrhosis
Hypercalcaemia:
Impairs Ca2+ absorption in LoH
IV fluids must be given as well
Dscribe the potency of thiazide diuretics
Give uses
Give common side effects
Potency:
Only inhibits 5% of Na+ reabsorption
Uses:
Hypertension (also cause vasodilation)
Side effects:
Higher incidence of hypokalaemia
Increases Ca2+ absorption
What are the similarities between K+ sparing diuretics and Aldosterone antagonists?
Both are mild diuretics (2% filtered load)
Both technially K+ sparing
Both reduce ENaC activity
Both can produce potentially life threatening hyperkalaemia (esp. if used with ACEI or K+ supplements)
What are the common uses for Aldosterone antagonists?
Conn’s syndrome:
Spironolactone best drug for Conn’s syndrome (Primary hyperaldosteronism)
Reduces aldosterone released from adrenal glands (Could be excess in Conn’s due to tumour or hyperplasia)
Ascites and oedema in cirrhosis
Used w/loop diuetics in Heart failure
What classes of diuretic are not currently used as diuretics?
Carbonic anhydrase inhibitors
Osmotic diuretics
What are the uses of carbonic anhydrase inhibitors and what is one side effect?
Glaucoma:
Can reduce aqueous humour formation in eye up to 50%
Side effect:
Can cause metabolic acidosis due to HCO3- loss in urine
What is an alternative use of Osmotic diuretics?
IV mannitol used to treat cerebral oedema
Outline how Nephrotic syndrome causes Oedema and ECF expansion and hence why it is suitable to treat with diuretics
Protein loss in urine
Therefore low plasma albumin, low oncotic pressure and oedema occurs
Reduced circulating volume activates RAAS and Na+ and water are retained leading to further ECF expansion and oedema
Diuretics used to treat (Loop diuretics) and reduce ECF volume
Outline why liver cirrhosis is treated with diuretics
Lowered albumin production of liver leads to oedema and reduced circulating volume
This in turn activates RAAS, causing ECF expansion and further oedema
Also, portal hypertension (Increases GI venous pressure) coupled with low oncotic pressure leads to ascities
Fluid loss due to ascites reduces circulatory volume, further activating RAAS and hence ECF expansion and oedema worsens further
Outline how loop and thizide diuretics can cause K+ loss and hypokalaemia
By blocking Na+ and water reabsorption in the LoH or Early DCT they increase Na+ and water delivery to the Late DCT/CD
3 Effects of this:
This increases flow rate, washing K+ away from principal cells, increasing the K+ gradient across them
Increased absorption of Na+ creates a more favourable electrical gradient for K+ secretion
Reduction of ECF due to diuretics activate RAAS and increase aldosteron release, leading to further increased Na+ absorption and K+ secretion
All lead to increased K+ loss leading to hypokalaemia
How do K+ sparing and aldosterone antagonist diuretics cause hyperkalaemia?
K+ sparing:
Block ENaC
Aldosteron antagonists:
Block action of aldosterone
Reduce activity of Na+/K+ ATPase, ENaC and K+ channels on principle cells
Effects:
Both these mechanisms lead to reduced Na+ absorption and K+ secretion
Hyperkalaemia results
How can we minismise the effects of diuretics on K+ levels?
Monitor electrolytes during diuretic therapy
Give K+ supplements with thiazide and loop diuretics
Use a combination of K+ sparing or aldosterone and thiazide or loop diuretics to balance effects
Whay is spironolactone the preffered drug for treating the oedema and ECF expansion of ascites?
Loop diuretics would be more effective but can cause hypokalaemia
Hypokalaemia can precipitate hepatic encephalopathy in a patient with advanced cirrhosis
What is hepatic encephalopathy?
Hint: Mechanisms and symptoms
General:
Reversible syndrome of impaired brain function due to advanced liver failure
Mechanism:
Liver not detoxifying ammonia causing elevated serum ammonia levels
Symptoms:
Confusion and coma
Constructional apraxia (Cannot build, assemble or draw things), flapping tremors
What factors might increase possibility of hyperkalaemia when treting with aldosterone antagonists (spironolactone)
K+ supplements
ACEI or Angiotensin receptor blockers
Impaired renal function
What are some of the adverse effects of diuretics not involving K+?
Hypovolaemia
Hyponatraemia
Increased uric acid in blood (precipitate gout attack)
Metabolic effects (Loop and thiazides):
- Glucose intolerance*
- LDL levels rise*
Erectile dysfunction (thiazides)
What are some other drugs with diuretic action?
Alcohol:
Inhibit ADH release
Lithium:
Inhibits ADH action
Coffee (Caffeine):
Increased GFR and decreased Na+ absorption
What are some diseases that cause diuresis/polyuria?
Mechanisms of each?
Diabetes mellitus:
Glucose in filtrate, osmotic diuresis
Diabetes insipidus:
Cranial - Decreased ADH release
Nephrogenic - Poor ADH response in CD
Psychogenic
Increased water intake
