Week 7 - UTIs and Diuretics Flashcards
1
Q
Describe the pathogenesis of UTIs
A
- Normal urinary tract is protected from infection by a variety of defence mechanisms
— Regular flushing during voiding, which removes organisms from the distal urethra
— Between voiding, these organisms may ascend the urethra - Commonest pathogens = gram-negative rods
— Particularly enterobactericeae (coliforms, especially E.coli)
— Coagulase-negative staphylococci cause infections in young women and in hospitalised patients - Host factors:
— Shorter urethra (more infections in females)
— Obstruction (enlarged prostate, pregnancy, stones, tumours)
— Neurological problems (incomplete emptying, residual urine)
— Ureteric reflux (ascending infection from bladder, especially in children) - Bacterial factors:
— Adhesion
• Fimbriae and adhesins allow attachment to urethral and bladder epithelium
— K antigen permits production of polysaccharide capsule
• Provides defence and protection
— Urease
• Produced by some bacteria
• Breaks down urea creating a favourable environment for bacterial growth
— Haemolysins
• Damage host membranes and cause renal damage
— Faecal flora
• Potential urinary pathogens colonise periurethral area
2
Q
What are the symptoms of bacterial cystitis?
A
Frequency and dysuria, often with pyuria and haematuria
- Lower urinary tract infection
3
Q
What are the symptoms of abacterial cystitis?
A
Frequency, dysuria, pyuria, haematuria but no significant bacteriuria
- Lower urinary tract infection
4
Q
What are the symptoms of prostatitis?
A
Fever, dysuria, frequency with perineal and low back pain
- Lower urinary tract infection
5
Q
What are the symptoms of acute pyelonephritis?
A
Symptoms of cystitis plus fever and loin pain
- Cystitis symptoms: Frequency and dysuria, often with pyuria and haematuria
- Upper urinary tract infection
6
Q
What are the symptoms of chronic interstitial nephritis?
A
Renal impairment following chronic inflammation
- Upper urinary tract infection
7
Q
What are the symptoms of covert bacteriuria?
A
Asymptomatic
- Detected only by culture
- Important in children and pregnancy
8
Q
How can you investigate for diagnosis of a UTI?
A
- Dipstick tests are available for the detection of:
— Blood
— Leukocyte esterase (indicating white blood cells)
— Nitrite (indicating the presence of nitrate-reducing bacteria) - Turbidity
- May include microscopy for:
— WBCs
— RBCs
— Squamous epithelial cells - The number of bacterial colonies cultured from urine specimens is estimated to give a bacterial count
— Significant bacteria: > 105 colony forming units of a single organism per ml of urine
— Interpretation of culture results depends on:
• Clinical details (symptoms, previous antibiotics)
• Nature and quality of specimen
• Delay in culture
• Species isolated
9
Q
When would you require repeat urine specimens?
A
- Low bacterial counts
- Evidence of contamination
- ‘Sterile pyuria’ – WBCs in the urine without bacterial growth, may be caused by:
- – Prior antibiotic
- – Urethritis (Chlamydia or gonococci)
- – Vaginal infection or inflammation
- – Fastidious organisms
- – Non-infective inflammation (e.g. tumours, chemicals)
- – Urinary tuberculosis
10
Q
How can you test for an uncomplicated UTI?
A
Infection indicated by nitrite/leucocyte esterase dipstick testing
- No culture needed
11
Q
How can you test for an complicated UTI?
A
Culture
12
Q
How do you treat an uncomplicated UTI?
A
- A short (typically 3 day) course of an oral antibacterial agent
- – E.g. trimethoprim or nitrofurantoi
- Increased fluid intake
13
Q
How do you treat a complicated UTI?
A
- 7 day course
- Trimethoprim, nitrofurantoin or cephalexin may be used
- – Amoxicillin is NOT appropriate because 50% of isolates are resistant
- Increased fluid intake
- Address underlying disorders
- Post-treatment follow-up culture
14
Q
When is a UTI complicated?
A
If patient is:
- Pregnant
- Male
- Underlying disorders
- Child
15
Q
How do you treat acute pyelonephritis?
A
- Treatment, initially systemic, for 10-14 days
- Possibly IV initially
- May use ciprofloxacin, cefuroxime, gentamicin (IV only)
16
Q
How do you treat a UTI in catheterised patients?
A
- Antimicrobial treatment is usually only recommended in patients with systemic features
- Catheter should be removed if possible
17
Q
When would you give prophylaxis for a UTI?
A
- 3 or more episodes in 1 year
- No treatable underlying condition
Give: single nightly dose of trimethoprim or nitrofurantoin
18
Q
Describe the use of loop diuretics
A
- Block Na-K-2CL transporter
- Secreted into the lumen of the PCT
- Travel downstream to act at the loop of Henle
- Very potent diuretics
- Have a diuretic effect, as well as vaso- and venodilatory effects
- Used to treat fluid retention and oedema in:
- – Nephrotic syndrome
- – Renal failure
- – Cirrhosis of the liver
- Useful in treatment of hypercalcaemia
19
Q
Describe the use of carbonic anhydrase inhibitors
A
- Not particularly potent
- Acts on the PCT
- Inhibit NaHCO3- reabsorption
- – As it inhibits carbonic anhydrase in brush border and PCT cell
- – There is less HCO3- in the glomerular filtrate so there is a reduced effect on Na+ ion reabsorption
- Increase excretion of HCO3- with accompanying Na+, K+ and water
- – Results in an increased flow of an alkaline urine and metabolic acidosis
- Plasma [HCO3-] declines during chronic use of these drugs because of the increased urinary excretion of HCO3-
- Not used as diuretics anymore, but used in the treatment of glaucoma
20
Q
Describe the use of thiazide diuretics
A
- Block Na-Cl cotransporter in DCT
- – Increases Na+ loss in urine
- Secreted into lumen in PCT
- Travel downstream to act at DCT
- Reduces Ca2+ loss in urine
- Less potent than loop diuretics
- Ineffective in renal failure
- Widely used in hypertension
- Higher incidence of hyperkalaemia
21
Q
Describe the use of K+ sparing diuretics
A
- Inhibitors of epithelial (ENaC) channels
— Mild diuretics
— Usually used in combination with K+ losing diuretics to minimise K+ loss
• Such as loop of thiazide diuretics - Aldosterone antagonists
— Best drug for treatment of hypertension due to primary hyperaldosteronism
— Preferred drug for ascites and oedema in cirrhosis
— Used in addition to loop diuretics in heart failure - Both groups:
— Reduce the loss of K+
— Reduce Na+ channel activity
— Are mild diuretics
— Can produce life-threatening hyperkalaemia
— Don’t use with K+ supplements
— Only use with normal renal function
22
Q
Describe osmotic diuretics
A
- Small inert molecules
- Increases plasma osmolarity thus drawing out fluid from tissues and cells
- Freely filtered in the kidney but not reabsorbed, so increases the osmolarity of the filtrate
- Acts by altering the driving force for renal water absorption, which is osmolarity
23
Q
How can loop and thiazide diuretics cause hypokalaemia?
A
Increased Na+ and H2O delivery to late DCT and CD causes:
- Faster flow rate of filtrate in tubule lumen
- – K+ secreted into lumen is washed away faster
- – Lower [K+] in lumen, so favourable chemical gradient for K+ secretion
- – Hence more K+ loss in the urine
- Increased Na+ absorption by principal cells
- – Favourable electrical gradient for K+ excretion
- – Hence more K+ loss in the urine
24
Q
How can diuretics cause hyperkalaemia?
A
May occur with K+ sparing diuretics
- Reduced activity of ENaC and Na-K-ATPase reduces Na+ absorption
- Hence reduces potassium loss in urine
25
Q
What are some adverse effects of diuretics?
A
- Potassium abnormalities
- Hypovalemia
— Especially loop diuretics
— Excessive loss of Na+ and water
— Monitor:
• Weight
• Blood pressure
• For signs of dehydration - Hyponatraemia
- Increased uric levels in the blood
— With thiazide and loop diuretics
— Can precipitate attack of gout - Erectile dysfunction
— Thiazide diuretics
26
Q
What other substances can cause diuresis?
A
- Alcohol: inhibits ADH release
- Coffee: increases GFR and decreases tubular Na+ reabsorption
- Other drugs: lithium, demeclocycline
- – Inhibit ADH action on collecting ducts
27
Q
What are some diseases that cause diuresis?
A
- Diabetes mellitus
- – Glucose in filtrate, so osmotic diuresis
- Diabetes insipidus (cranial)
- – Decreased ADH release from posterior pituitary
- Diabetes insipidus (nephrogenic)
- – Poor response of collecting ducts to ADH
- Psychogenic polydipsia
- – Increased intake of fluid
28
Q
What can diuretics be used to treat?
A
- Hypercalcaemia
- – Loop diuretics promote calcium excretion in the loop of henle
- Hypertension
- – Thiazide diuretics
- – Spironolactone
- – Resistant hypertension
- Acute pulmonary oedema
- – IV furosemide
- Kidney failure
- – Unable to excrete Na+ and H2O
- – Need loop diuretics
- Conditions with ECF expansion and oedema
- – Congestive heart failure
- – Nephrotic syndrome
- – Cirrhosis with ascites and oedema
29
Q
How does congestive heart failure cause ECF expansion and oedema?
A
- Increased systemic venous pressure leads to oedema
- – Fluid moves from intravascular to interstitial compartment
- Drop in cardiac output with reduced renal perfusion
- Leads to activation of RAAS
- – Na+ retention causes expansion of ECF
30
Q
How does nephrotic syndrome cause ECF expansion and oedema?
A
- Glomerular disease that leads to increased glomerular basement membrane permeability to protein
- Proteins are filtered and lost in urine, causing:
- – Low plasma albumin which results in low plasma oncotic pressure and hence peripheral oedema
- Reduced circulatory volume
- RAAS activated
- Na+ and water retention
- Expansion of ECF and more oedema
31
Q
How does cirrhosis cause ECF expansion and oedema?
A
- Reduced albumin synthesis in liver
- – Causes low plasma albumin which results in low plasma oncotic pressure and hence peripheral oedema
- Portal hypertension
- – Causes increased venous pressure in splanchnic circulation
- – High venous pressure and low oncotic pressure
- – Movement of fluid from peritoneal capillaries to peritoneal cavity (transudate)
- – Ascites (fluid in peritoneal cavity)
- Oedema and ascites lead to reduced circulatory volume:
- – RAAS activated
- – Na+ and water retention
- – Expansion of ECF and worsening oedema and ascites
