Pathology and Therapeutics

for Pharmacists
A basis for clinical pharmacy practice

THIRD EDITION

Russell J Greene
BPharm MSc PhD MRPharmS
Senior Lecturer in Clinical Pharmacy
Former Head, Pharmacy Practice Group
Department of Pharmacy
King’s College London
University of London
UK

Norman D Harris
BPharm PhD DIC
Emeritus Reader in Pharmaceutics
Department of Pharmacy
King’s College London
University of London
UK

London • Chicago
 Published by the Pharmaceutical Press
An imprint of RPS Publishing

1 Lambeth High Street, London SE1 7JN, UK

100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, USA

© Russell J Greene and Norman D Harris 1993, 2000, 2008

is a trade mark of RPS Publishing

RPS Publishing is the publishing organisation of the Royal
Pharmaceutical Society of Great Britain

First edition published by Chapman & Hall 1993

First published in paperback 1994
Reprinted 1995
Reprinted by the Pharmaceutical Press 1996, 1997, 1998
Second edition published 2000
Reprinted by the Pharmaceutical Press 2003, 2006
Third edition published 2008

Typeset by J&L Composition, Filey, North Yorkshire

Printed in Great Britain by Cambridge University Press,
Cambridge

ISBN 978 0 85369 690 2

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duced, stored in a retrieval system, or transmitted in any form
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copyright holder.
The publisher makes no representation, express or implied,
with regard to the accuracy of the information contained in this
book and cannot accept any legal responsibility or liability for
any errors or omissions that may be made.
The rights of Russell J Greene and Norman D Harris to be iden-
tified as the authors of this work has been asserted by them in
accordance with the Copyright, Designs and Patents Act, 1988.

A catalogue record for this book is available from the British

Library.

Disclaimer

The drug selections and doses given in this book are for illustration only. The authors and publishers
take no responsibility for any actions consequent upon following the contents of this book without
first checking current sources of reference.
All doses mentioned are checked carefully. However, no stated dose should be relied on as the basis for
prescription writing, advising or monitoring. Recommendations change constantly, and a current copy of
an official formulary, such as the British National Formulary or the Summary of Product Characteristics,
should always be consulted. Similarly, therapeutic selections and profiles of therapeutic and adverse
activities are based upon the authors’ interpretation of official recommendations and the literature at the
time of publication. The most current literature must always be consulted.
 932 Chapter 14 • Renal system

propantheline (contra-indicated in bladder benign if restricted to a single attack at that site.

outflow obstruction) or catheterization may also Conversely, infection of the kidney (upper
assist the passage of stones. Penicillamine will urinary-tract infection or pyelonephritis) is
help to dissolve cystine stones. Reducing always serious and has systemic complications. It
urinary urate levels with allopurinol may help. may even lead to CRF: indeed, chronic
Alkalinization of the urine, e.g. with potassium pyelonephritis accounts for some 10% of all
citrate mixture, will also reduce hypercalciuria ESRD.
and in turn the formation of both urate and However, urinary-tract infection and
cystine stones. Urinary acidification, e.g. with pyelonephritis are not completely distinct. Most
ammonium chloride, will minimize phosphate kidney infections are presumed to have ascended
stone production. from asymptomatic, untreated or inadequately
For oxalate stones, sodium restriction and treated urinary-tract infection, and this retro-
thiazides are used both to reduce urinary calcium grade infection is encouraged by the urinary
(thiazides promote tubular reabsorption of stasis, which can result from obstruction.
calcium) and to increase urine flow. It is impor- Repeated or serious urinary-tract infection can
tant not to reduce dietary calcium in an attempt itself lead to obstruction by causing ureteric
to treat hypercalciuria, because, paradoxically, fibrosis and stricture (narrowing). The patholog-
this tends to increase future stone formation and ical spectrum, from asymptomatic bacteriuria to
also cause loss of calcium from bones. what is still termed chronic pyelonephritis, is
Nephrostomy may permit extraction of larger illustrated in Figure 14.21.
pelvic stones and drainage in hydronephrosis. Because pyelonephritis causes inflammatory
Stones may be ultrasonically disrupted by extra- damage there is also some pathological similarity
corporeal shock-wave lithotripsy (ESWL) and the to such conditions as nephrotoxicity, analgesic
fragments passed out in the urine. Fibre-optic nephropathy, reflux nephropathy and the renal
ureteroscopy, which requires general anaesthetic, manifestations of connective tissue disorders,
may be required. Open surgery is rarely necessary. e.g. SLE. The generic term interstitial nephritis is
In reflux nephropathy prompt treatment of often preferred.
infections and adequate control of hypertension
are likely to prevent progression. Surgery is rarely
Urinary-tract infection
indicated, except for reconstruction of a congen-
itally abnormal vesicoureteric junction. Because of the close pathogenetic links between
Renal colic is treated with either pethidine or, urinary-tract infection, reflux nephropathy,
increasingly, an NSAID (diclofenac), which obstruction and pyelonephritis, some of the
reduces ureteric spasm in addition to its anal- general features of urinary-tract infection are
gesic effect. IV fluids are used to promote urine discussed here so as to present a complete
flow, especially as the patient is likely to be picture of renal system infections. Full details of
extremely nauseous. urinary-tract infections, especially their investi-
In all methods employing treatments to gation and management, are given in Chapter 8.
encourage urine flow, it is of course important to
ensure initially that there is not complete Aetiology and pathology
obstruction. Urine is normally sterile. The faecal commensal
Escherichia coli is responsible for acute infection in
75% of those cases where a urinary organism is
Infection identified. Less common pathogens include
staphylococci, faecal streptococci, Proteus and
As with obstruction, there is a significant differ- Klebsiella. Non-specific urethritis (i.e. non-
ence between infections of the lower and upper gonococcal) is usually caused by Chlamydia spp.
renal systems. Lower urinary-tract infection (e.g.
urethritis, cystitis) causes discomfort, inconve- Women. Even with the strictest hygiene,
nience and not a little pain, but is essentially urinary-tract contamination with skin commen-
 Important renal diseases 933

SIMPLE
ASYMPTOMATIC ACUTE CHRONIC
BACTERIAL
BACTERIURIA PYELONEPHRITIS PYELONEPHRITIS
CYSTITIS

ABACTERIAL
CYSTITIS

Symptoms
local     
systemic     

Treatment
fluid     
alkali  ? ?  
antimicrobial   oral oral oral/parenteral

Complications
/? stones? chronic renal failure
obstruction?

Prognosis
good good good good if single variable
attack

Figure 14.21 Spectrum of renal tract infection. , absent (symptom) or useless (treatment), , minor (symptom) or useful
(treatment); , moderate; , substantial; ?, uncertain.

sals or faecal organisms is difficult to avoid in abdominal ureteric compression. On the other
women. This is due to the anatomical proximity hand, no organism can be found in up to 50% of
of the urethral and anal openings, and the rela- women who do have symptoms of cystitis; this is
tively short urethra. Simple urinary-tract infec- known as abacterial cystitis (or ‘urethral
tion is far more common among women than syndrome’).
men.
The route of infection may be anus– Men. Infection in males is much rarer and
vagina–vulva–urethra. Vaginal secretions, urine always requires investigation. Sexually trans-
and the urinary tract all normally have protec- mitted non-specific urethritis is the most
tive antimicrobial properties, e.g. mucosal IgA, common cause in young men and chronic bac-
locally acidic pH, frequent flow. Thus, recurrent terial prostatitis in older men.
infection suggests a breakdown in these defence
mechanisms, e.g. obstruction, or a protected Both sexes. In the elderly of either sex the
focus of infection, e.g. infected stones. Persisting prevalence of urinary-tract infection may rise to
vaginal organisms may be introduced into the 30% and this is a particular problem in institu-
urethra mechanically, especially during inter- tions. Catheterization alone carries a risk of infec-
course – hence the rather quaint but now tion variously estimated at between 2% and 20%.
distinctly anachronistic term ‘honeymoon In diabetics, reduced host defence and glycosuria
cystitis’. Urinary-tract infection is more common predispose to urinary bacterial growth.
among postmenopausal women owing possibly
to a loss of protection afforded by oestrogens. Clinical features and course
Although bacteriuria is found in about 5% of The hallmark of acute urethritis/cystitis is an
adult women, few of these suffer symptoms. intense burning sensation on micturition, to
Such asymptomatic or covert bacteriuria gener- which the simple term dysuria fails to do justice.
ally does not require treatment except during The condition may be exacerbated by a more
pregnancy, where there is a 30% chance of acid urine resulting from local bacterial metabo-
progression to acute pyelonephritis due to intra- lism. Urinary frequency is common and there
 934 Chapter 14 • Renal system

may be suprapubic pain or discomfort. Pyuria, require prophylactic therapy. For details of treat-
purulent discharge or even haematuria may also ment, see Chapter 8.
occur but, although alarming and requiring
investigation, are not necessarily sinister. There
Acute pyelonephritis
are no systemic signs. The elderly commonly
present with acute confusion, fever, malaise or Like lower urinary-tract infection, most cases of
anorexia but few specific urinary symptoms, acute pyelonephritis (APN) occur in women. E.
making it easy to miss during examination. It is coli is the usual culprit, but Proteus, Staphylo-
also difficult to spot in young children if not coccus and Pseudomonas are found more
suspected. commonly than in simple urinary-tract infec-
Urinary-tract infection is usually self-limiting tion. Tubular inflammation causes polyuria and
within a few days, especially if fluid intake is a dilute urine but severe cases may progress to
promptly increased substantially. It may have no acute oliguric renal failure.
complications in the absence of any other renal
abnormality. However, recurrence is common Clinical features
owing either to infection with a different An acute onset of severe loin pain is accompa-
organism, or to relapse or re-infection with the nied by systemic features such as fever, nausea
same organism. The latter situation suggests the and vomiting. There may also be lower urinary-
presence of a complicating factor that is tract infection symptoms of cystitis and
preventing complete eradication. urethritis (Figure 14.20). Rarely, if both kidneys
are affected, tubular oedema and inflammatory
Investigation exudate may cause intrarenal obstruction with
Two things must be determined: (i) which acute post-renal failure.
organism is responsible; and (ii) are there any
underlying causes or correctable complications? Management
The collection of urine samples and the indica- Prompt appropriate oral antimicrobial therapy
tions for further investigation are discussed in and an increased fluid intake are always indi-
Chapter 8. cated. The same agents are used as in urinary-
tract infection. However, close attention to
Management microbiological results is vital because of the
In the management of urinary-tract infection greater likelihood of unusual or resistant organ-
the aims are to: isms and the importance of characterizing recur-
rence as either relapse, i.e. the same organism, or
• reduce the risk of renal damage.
re-infection possibly with another.
• provide symptomatic relief.
Most patients have a single attack of APN
• render the urine sterile.
and recover completely, but recurrent attacks
• provide prophylactic therapy.
or persistent asymptomatic bacteriuria require
The first of these is achieved by prompt atten- further investigation. If the recurrence is a
tion and full investigation when appropriate. relapse with the same organism, either the
General measures include increasing the fluid antimicrobial therapy was inadequate or
intake substantially to promote urine flow, and there may be obstructive/reflux abnormalities.
providing advice on hygiene. For women, advice Frequent re-infection with different organisms
includes front-to-back wiping after defaecation or strains suggests that the host defences are
(although the role of this has been disputed), defective, and that prophylactic antimicrobial
and micturition before and after coitus. Frequent therapy should be considered. This can be
recurrence or relapse in the absence of obstruc- continuous low-dose therapy, or intermittent
tive or other correctable complications may 5-day full-dose courses at the onset of symp-
 Important renal diseases 935

toms, which the patient can be instructed to such as polyuria or nocturia, because the renal
initiate. damage is primarily tubular. Early reflux damage
may initiate the hypertension–renal failure
vicious cycle, and sometimes a history of related
Reflux nephropathy (chronic pyelonephritis)
childhood illnesses such as enuresis or cystitis
Definition may be traced. Diagnosis and investigation
The term chronic pyelonephritis has traditionally involve urography, urine microbiology and renal
been used to describe a condition diagnosed radi- function tests.
ologically where one or both kidneys appear irreg-
ular, shrunken and scarred. However, because Management
evidence is accumulating of a strong association In the absence of renal impairment, all that may
with reflux or infection, the term reflux be required is regular monitoring of blood pres-
nephropathy is now preferred. Although most sure, urine microbiology and renal function.
cases do not progress to renal failure, it can be Infective episodes must be treated promptly as
extremely difficult to treat, and renal scarring is for APN, and appropriate antimicrobial prophy-
present in up to 20% of patients starting dialysis. laxis may be indicated if bacteriuria cannot be
eliminated. In children, surgery to correct reflux
Pathogenesis may be necessary.
The relative contributions of chronic infection
and sterile reflux (causing simple pressure Course and prognosis
damage) are still uncertain. Many patients have Most patients have stable disease, especially if
neither bacteriuria nor a history of urinary-tract their BP and bacteriuria are managed success-
infection, and although urinary-tract infection fully. Recurrent infective exacerbations carry a
and APN are far more common in women, poorer prognosis, but only about 1% of patients
reflux nephropathy shows equal sex distribu- progress to CRF.
tion. One form may result from vesicoureteric
reflux starting in the very young, and this has a
poorer prognosis because it may be silent or Glomerular disease
undiagnosed for long periods. In adults, recur-
rent urinary-tract infection or APN may be Glomerular disease invariably affects both
responsible. kidneys. Glomeruli seem especially sensitive to
Bacterial reflux nephropathy commonly inflammatory immune damage, and most forms
involves more virulent Gram-negative organ- of glomerular disease involve immunological
isms, including Pseudomonas, and persistent mechanisms. Glomerulonephritis (GN) is the
infection with relapses is common. In contrast to single most important cause of CRF.
the urinary tract the renal pelvis seems to have
no natural antibacterial defences (presumably
Classification
evolution never anticipated organisms there).
There may even be factors that encourage the For such a small and apparently simple structure
microbial persistence, so complete eradication is the glomerulus presents inordinate pathological
difficult. complexity. Descriptions of glomerular disease
have a long history in medicine, and under-
Clinical features and investigation standing of the condition is confounded by the
The condition may be asymptomatic or may numerous methods of classification. Moreover,
present as proteinuria, hypertension or recurrent increasingly sophisticated microscopy and
urinary-tract infection. Rarely, the first indica- immunological techniques continue to identify
tion may be symptoms of incipient renal failure new criteria and subgroups. Thus, in addition to