Biochemistry and Microbiology Flashcards
from what is GFR calculated
from 4 parameters
- serum creatinine
- age
- gender
- race
where does the urea cycle occur
in the liver
what is the down fall of using serum creatinine to calculate GFR
is not useful for showing mild renal impairment
i.e. Creatinine will rise but not greatly.
Small change despite steep fall in GFR.
what is ‘clearance’
the volume of plasma that is theoretically cleared of a substance per minute.
how is urinary creatinine clearance calculated
[creatinine]urine x urine volume / [creatinine]serum x duration of collection
what are confounders of serum creatinine
muscle mass»_space; bigger your muscle mass is the more production of creatinine than a smaller person
diet
what normally happens to plasma proteins in the kidney
they are normally retained
Ix for proteinuria
albumin/creatinine ratio or
protein/creatinine ratio
what levels of protein in the urine is suggestive of significant glomerular damage
Protein >150mg/day in the urine
what are the different causes of proteinuria
Overflow
Glomerular
what happens in overflow proteinuria and what can cause this
problem is that you are overproducing one particular protein, glomerular basement cannot handle protein load, leak protein into the filtrate, ability to reabsorb is diminished as it cannot handle volume of protein
multiple myeloma
what happens in glomerular proteinuria and what can cause this
normal amount of protein, but glomerulus not working as well, protein let through, overwhelms tubules again
albuminuria
in multiple myeloma, what causes kidney impairment
light chain deposition
what is seem on an x-ray in multiple myeloma
Pepper pot appearance/punched out lesions in the skull
what is nephrotic syndrome
triad
- proteinuria
- hypoalbuminaemia
- oedema
what causes the nephrotic syndrome
pouring out protein in the urine in severe cases
body cannot make enough protein to replace what you are losing
balance of osmotic forces changes
more fluid in interstitial space
» nephrotic syndrome
what does microalbuminuria mean
excretion of albumin in abnormal quantities but still below the limit of protein detection by dipstick
what is microalbuminuria the earliest expression of
diabetic nephropathy
why is microalbuminuria treated
to reduce risk of progression
Tx of microalbuminuria in DM
ACE-i or ARB
irrespective of blood pressure
manage CV risk factors - stop smoking, reduce cholesterol, consider aspirin
what is the target BP in DM with kidney problems but NO proteinuria
130/80
what is the target BP in DM with kidney problems WITH proteinuria
125/75
what are the 3 categories of problem in tubular function in oliguric patient
pre-renal
post-renal
renal
what mechanism and example of pre-renal problem
reduced renal perfusion, kidney’s fine but not perfused properly
e.g. Blood loss, hypovolaemia
what mechanism and example of post-renal problem
an obstruction to urinary outflow tract, ureter to urethra
e.g. stones, malignancy
what mechanism and example of renal problem
intrinsic kidney tissue damage
e.g. glomerulonephritis
what does the kidney produce and where do these products work
erythropoietin»_space; bone marrow
1,25 Dihydroxycholecalciferol»_space; gut
renin»_space; converts angiotensiogen to angiotensin I
how can tubular function be calculated
urine osmolality v serum osmolality
what is the bacteria in the normal urinary tract
Urine in kidneys, ureters and bladder is sterile
Lower end of the urethra is colonised by bowel flora i.e. Coliforms and enterococci
what is definition of UTI
The presence of micro-organisms in the urinary tract that are causing clinical infection
what is a lower UTI
infection confined to the bladder (cystitis - inflammation of the bladder)
what is a upper UTI
infection involving the ureters +/- the kidneys (pyelonephritis - inflammation of the kidney)
why is it important where the UTI is
influences the treatment
what is a complicated UTI
UTI complicated by systemic sepsis (infection getting into the blood) or urinary structural abnormality or stones
- have to use longer course of antibiotics
what is Bacteriuria
the presence of bacteria in the urine
does not always mean infection, esp. in elderly patients or patients with catheters
is cystitis always due to infection?
no, there are a number of causes but is commonly due to UTI
why do women get UTI more than men
- short wide urethra
- proximity of urethra to anus
- increased risk with sexual activity
- pregnancy (many women presenting with first UTI when pregnant)
who gets UTIs
common
W > M
Catheterised patients
Patients with abnormalities of the urinary tract (e.g. horseshoe kidney)
what are the routes of infection for UTI
Ascending infection (more important/commoner)
From the bloodstream (descending route of infection)
how does ascending infection work
bacteria from bowel → perineal skin → lower end of urethra → bladder → ureters → kidneys
how does UTI via the bloodstream occur
patient with bacteraemia / septicaemia from another focus of infection → bacteria in blood → seeded into kidneys → multiple small abscesses → bacteria in urine
what commonly cause UTI
‘Coliforms’:
E.coli - commonest cause
Klebsiella sp.
Enterobacter sp.
Proteus sp.
Other coliforms
what is the commonest cause of UTI
E.coli
how do coliforms appear on gram stain
gram -ve bacilli
what is Proteus sp. associated with
formation of stone (calculi)
features of Proteus sp. and how it causes stones
foul smelling
Produces urease which breaks down urea to form ammonia, which increases urinary pH - precipitation of salts
what are enterococcus spp.
types of “streptococci” that live in the GI tract that can also cause UTI
e.g.
Enterococcus faecalis
Entercoccus faecium
what staph is the most common staph to cause UTI and features of it
Staphylococcus saphrophyticus
- a type of coagulase negative staph
- usually affects women of child bearing age
can staph. aureus cause UTI?
yes but it is less common than coliforms and Staphylococcus saphrophyticus
why is Pseudomonas aeruginosa difficult to treat
resistant to most oral antibiotics except ciprofloxacin
features of Pseudomonas aeruginosa
Gram negative bacillus but not a coliform
Associated with catheters and UT instrumentation
Sx of UTI
dysuria (pain passing urine)
frequency of urination / nocturia
haematuria
fever } suggest involvement
loin pain} of
rigors } upper urinary tract
what is ciprofloxacin associated with
C. Diff infection
what are problems with collecting a urine sample for UTI Ix
want to test bladder urine, not the lower end of the urethra which has bacteria normally
first urine passed is most likely to be contaminated with bacteria normally in the urethra
how should a urine sample for UTI Ix be collected
Collecting a mid-stream specimen of urine (MSSU)
- Wash perineum / urethral meatus with sterile saline (not antiseptic - could be passed into urine and kill bacteria of UTI)
- Give patient a sterile foil bowl
- First urine passed into toilet
- Next part collected in foil bowl
- Last urine passed in toilet
what are other ways urine can be obtained
“Clean catch” urine
- children, elderly; nurse tries to catch midstream urine.
Bag urine (babies)
- often contaminated with bowel flora
- negative culture result useful
Catheter specimen of urine (CSU)
Suprapubic aspiration
- normally used after Bag urine in children if bag urine is +ve
what in a dip stick urine testing can indicate infection
Leukocyte esterase
- Indicates the presence of leukocytes (WBC) in the urine
Nitrites
- Nitrites indicate the presence of bacteria in the urine
- Some bacteria can reduce nitrates to nitrites – mainly coliforms – Enterococcus spp. do NOT give positive test
Protein
Blood
when is microscopy of the urine down
only done on selected (urgent) cases
look for presence of polymorphs (pus cells), bacteria +/- red cells
what is Kass’s Criteria
> 10 to the power of 5 organisms / ml
significant =probable UTI
what is ESBL-producing bacteria
Makes bacteria resistant to ALL cephalosporins and to almost all penicillins
Carried on a plasmid, which often carries genes for other resistance too (e.g gentamicin, ciprofloxacin)
what can be used to treat ESBL-producing bacteria
Nitrofurantoin (oral), pivmecillinam (oral) fosfomycin (oral), temocillin (IV) meropenem(IV) ertapenem (IV)
where is ESBL-producing bacteria found
imported chicken
what is Carbapenemase-producing Enterobacteriaceae (CPE)
Gram negative (coliform) bacilli that are resistant to meropenem This usually means that they are effectively resistant to ALL current antibiotics
what microorganisms can be found in the urine after travelling to india
Klebsiella pneumoniae
Providencia rettgeri
how long does an uncomplicated UTI in women need to be treated for
3 days
why is amoxicillin a 1st line drug in UTI but what are its drawback
Can be given orally or IV
Safe, even in pregnancy
Range of organisms treated
- Enterococcus faecalis
- Some coliforms, but >50% E coli now resistant, and many other coliforms also resistant
- not good for empirical treatment
what is given for empirical treatment of UTI
Trimethoprim (oral)
features of Trimethoprim
Safe, but avoid in 1st trimester (3 months) of pregnancy
Can be given as co-trimoxazole (IV or oral) but risk of Stevens-Johnson syndrome
Range of organisms treated:
most coliforms, Staph aureus incl. MRSA but not Pseudomonas sp.
when is Nitrofurantoin useful
in lower uncomplicated UTI as only reaches effective concentrations in bladder urine
Range of organisms treated:
Most coliforms, Enterococci, Staph aureus incl MRSA, but not Proteus sp and Pseudomonas sp.
when should Nitrofurantoin be avoided
Avoid in late pregnancy (can cause neonatal haemolysis), breast feeding and children
features of Gentamicin
Hospital use only (has to be given IV)
Range of organisms treated: Most coliforms, PSEUDOMONAS sp, Staph aureus incl MRSA, but not enterococci
Very effective drug in severe Gram negative (coliform-related) sepsis
Should be prescribed for 3 days ONLY - due to toxicity
complications of gentamicin and when is it NOT used
risk of toxicity causing renal and VIIIth nerve damage (deafness and balance problems)
Avoid in pregnancy
Dose of gentamicin
Given once daily – 7mg/kg (ideal body weight) then measure a blood level 6-14 hours later
what is Pivmecillinam used for
treating lower uncomplicated UTI
often used in elderly in community
what antibiotics have some action against coliforms that produce ESBLs
Pivmecillinam
Temocillin
when is Temocillin given
Useful for treating complicated UTI/urosepsis in patients whose renal function is too poor for gentamicin
when is Cefalexin used
in pregnancy
features of Co-amoxiclav
associated with C. Diff
BUT safe to use in pregnancy
features of Ciprofloxacin
risk of C.Diff infection
not used in pregnant women or young children
when do you need to use Ciprofloxacin
Pseudomonas sp infection
- only oral drug that can treat it
Empirical antibiotic treatment for UTI
Female lower UTI
- Trimethoprim or nitrofurantoin orally (3 days)
Uncatheterised male UTI
- Trimethoprim or nitrofurantoin orally (7 days)
Complicated UTI or pyelonephritis (GP)
- Co-amoxiclav or co-trimoxazole (14 days)
Complicated UTI or pyelonephritis (Hospital)
- Amoxicillin and gentamicin IV for 3 days (cotrimoxazole and gentamicin if penicillin allergy)
what is Asymptomatic bacteriuria
Significant bacteriuria (>10 to the power of 5 orgs/mL)
Patient is asymptomatic, condition detected incidentally.
No pus cells in urine
Antibiotic treatment often NOT required, especially in the elderly
May recur even if antibiotic treatment is given
when are pregnant women screened for Asymptomatic bacteriuria
All pregnant women screened at 1st antenatal visit
what can happen is asymptomatic bacteriuria is left untreated in pregnant females
Usually treated with antibiotics in pregnancy.
If left untreated:
- 20-30% progress to pyelonephritis
- May lead to intra-uterine growth retardation (IUGR) or premature labour
what is Abacterial cystitis/ Urethral syndrome
Patient has symptoms of UTI
Pus cells present in urine, but no significant growth on culture
May be an early phase of UTI
May be due to urethral trauma - “honeymoon cystitis”
May be due to urethritis caused by chlamydia, gonorrhoea
what can provide symptomatic relief
Alkalinising the urine may help
when should UTI in catheterised patients be treated
> 10 to the power of 5 orgs/mL
ONLY given antibiotics if there is supporting evidence of UTI (fever, symptoms etc.)
