Embed Size (px)
Citation preview
45
CLINICO-EPIDEMIOLOGICAL AND EXPERIMENTAL
OBSERVATIONS ON FELINE LOWER URINARY
TRACT DISEASE AMONG DOMESTICATED CATS
By
ABEERA NAUREEN
2007-VA-541
A THESIS SUBMITTED IN THE PARTIAL FULFILLMENT
OF THE REQUIREMENT FOR THE DEGREE
Of
DOCTOR OF PHILOSOPHY
In
CLINICAL MEDICINE
Department of Clinical Medicine and Surgery
FACULTY OF VETERINARY SCIENCES
UNIVERSITY OF VETERINARY AND ANIMAL
SCIENCES, LAHORE.
2015
46
47
To
The Controller Examinations,
University of Veterinary and Animal Sciences, Lahore
Pakistan
We, the Supervisory Committee, certify that the contents and form of thesis
submitted by Ms. Abeera Naureen (Registration # 2007-VA-541) have been found
satisfactory and recommend that it be processed for the evaluation by the External
Examiner (s) for the award of the Degree.
SUPERVISORY COMMITTEE:
Chairman:
Prof. Dr. Muhammad Sarwar Khan
Member:
Prof. Dr. Muhammad Arif Khan
Member:
Prof. Dr. Azhar Maqbool
48
DEDICATED
To
MY PARENTS,
HUSBAND AND SON
49
ACKNOWLEDGEMENTS
All extols and recognition for Almighty Allah, Who is the entire source of all
knowledge and wisdom endowed to mankind. I offer my humblest gratitude from the
deep sense of heart to the Holy Prophet, MUHAMMAD (Peace be Upon Him) Who
is, forever source of guidance and knowledge for humanity.
First and foremost, I would like to express my heartiest gratitude and deep
sense of obligation to my worthy supervisor and gracious mentor Prof. Dr.
Muhammad Sarwar Khan, Professor, Department of Clinical Medicine & Surgery,
for his leadership and support that he provided over the past several years. Without
his insightful direction, many of the results presented in this dissertation would not
have been possible. Not only that I am grateful to him for helping me conceive the
idea of this research but also for sharing many thought-provoking discussions in the
realization of final manuscript.
It gives me a momentous pleasure in transcribing my whole hearted thanks to
the members of my Supervisory Committee, Prof. Dr. Muhammad Arif Khan,
Professor and Chairman, Department of Clinical Medicine & Surgery, and Prof. Dr.
Azhar Maqbool, Professor, Department of Parasitology, for their able guidance,
keen interest, constructive criticism and ever-encouraging attitude throughout the
course of investigation and write-up of dissertation manuscript.
I am extremely indebted to my parents and husband for allowing me to usurp
countless hours of family time to complete the arduous task of research work and
write-up of this manuscript. In the end, I would like to dedicate this dissertation to my
parents, husband and son.
Abeera Naureen
50
CONTENTS
DEDICATION (i)
ACKNOWLEDGMENT (ii)
LIST OF TABLES (iii)
LIST OF FIGURES (iv)
LIST OF APPENDICES (v)
Sr. NO. CHAPTERS PAGE
NO.
1. INTRODUCTION 1
2. REVIEW OF LITERATURE 5
3. MATERIALS AND METHODS 26
4. RESULTS 45
5. DISCUSSION 104
6. SUMMARY 117
7. LITERATURE CITED 120
APPENDICES 133
51
LIST OF TABLES
TABLE
NO.
TITLE PAGE
NO.
1 Signalments, body weight and duration of illness of domesticated
cats (n = 502) affected with idiopathic feline lower urinary tract disease (iFLUTD)
55
2 General medical history of client-owned domesticated felines (n =
502) affected with idiopathic feline lower urinary tract disease
(iFLUTD)
57
3 Cardinal parameters of client-owned domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD)
58
4 Absolute number and frequencies of important clinical signs
(dysuria, pollakiuria, uretheral obstruction, exclusive licking,
vocalization, vomiting, dehydration, lethargy, anorexia, diarrhea,
and stranguria) noted among client-owned domesticated cats (n =
502) affected with idiopathic feline lower urinary tract disease (iFLUTD)
60
5 Urinalysis results of client-owned domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease
(iFLUTD)
61
6 Hemato-biochemical values of client-owned domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease (iFLUTD)
62
7 Descriptive Statistics of Body Weight (kg) and age (years) of
domesticated cats (n = 502) affected with idiopathic feline lower
urinary tract disease (iFLUTD) with respect to depression (viz., mild, moderate or severe)
64
8 Descriptive statistics of body weight (kg) and age (years) of cats
(n = 502) affected with idiopathic feline lower urinary tract
disease (iFLUTD) with respect to hyperemic external urethral orifice with (n = 133) and without (n = 369) urethral plug
65
9 Descriptive statistics of body weight (kg) of domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease
(iFLUTD) with respect to species (Long Hair Domestic, LHD;
Short Hair Domestic, SHD; Non-Descript, ND; Persian and Siamese)
67
52
10 Frequency distribution of depression status among domesticated
cats (n = 502) affected with idiopathic feline lower urinary tract
disease (iFLUTD) with respect to different cities (Faisalabad, Islamabad, and Lahore; Pakistan)
68
11 Frequency distribution of depression among domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease
(iFLUTD) with respect to some of the important factors being observed according to proforma designed (Appendix)
72-73
12 Frequency distribution of depression among domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease
(iFLUTD) and Hyperemic external urethral orifice without
urethral plug (HEUOWUP) with respect to some of the important
factors being observed according to proforma designed
(Appendix)
77-78
13 Frequency distribution of depression among domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease
(iFLUTD) and Hyperemic external urethral orifice with urethral
plug (HEUO-UP) with respect to some of the important factors being observed according to proforma designed (Appendix)
79-80
14 Different diagnostic tests (viz., Urinalysis, Hyperkalemia,
Clinical Signs, Radiography, Serum cortisol levels, and
Ultrasonography) performed against the diagnosis of idiopathic feline lower urinary tract disease (iFLUTD)
94
15 Performance and Kappa (agreement) statistics for different
diagnostic tests (viz. Urinalysis, Hyperkalemia, Clinical Signs,
Radiography, Serum cortisol levels, and Ultrasonography)
performed for the diagnosis of idiopathic feline lower urinary
tract disease (iFLUTD)
95
16 Evaluation of sensitivity and specificity of diagnostic tests (viz.,
Hyperkalemia, Clinical signs, Radiography, Serum crortisol
levels and Ultrasonography) with that of the standard (Gold
standard; Urinalysis was taken as the gold standard) against idiopathic feline lower urinary tract disease (iFLUTD)
96
17 Summary of pharmaceutical preparations administered to cats (n
= 27) experimentally affected with idiopathic feline lower urinary
tract disease (iFLUTD)
99
18 The frequencies of different clinical signs appeared during study
period and post-treatment observation period among 27 male cats
100
53
19 Range of hemato-biochemical profiles of male cats (n = 27)
before (day - 0), during (3 months of diet experimental trial) and
post-therapy observation period
101
20 Hemato-biochemical values of cats (n = 27) affected with lower
urinary tract disease
102
21 Therapeutic assessment of Pentosan polysulfate sodium (PPS)
during and after completion of therapy along with comparison of
effect of food viz-a-viz development of interstitial cystitis (IC)
and cortisol level (CL) viz-a-viz clinical severity scores (CSS)
during and after therapy completion in cats (n = 27) affected with
idiopathic Feline Lower Urinary Tract Disease (iFLUTD)
103
54
LIST OF FIGURES
Sr. No. Title Page No.
01 Notice angry external urethral orifice with urethral plug in a
cat affected with lower urinary tract disease
47
02 Notice angry external urethral orifice with urethral plug in a
cat affected with lower urinary tract disease
47
03 Surgical removal of a urolith from urinary bladder of a cat 48
04 Wafer like urolith surgically removed from urinary bladder of
a cat
48
05 Notice crystaluria in a urine sample collected through
cystocentesis (centrifuged 3500rpm-5 min)
49
06 Photomicrograph of Struvite crystals in cat affected with lower
urinary tract disease (x 20, and x 40)
50
07 Right lateral view of a cat demonstrating fully distended
bladder displaced the kidney anteriodorsally
51
08 Radiograph of a cat demonstrating urine filled distended
bladder with renomegaly (size of kidney is equal to 3
vertebrae).
51
09 Ultrasonogram of a cat with LUTD A dilated pelvis indicative
of renomegaly
52
10 Ultrasonogram of urinary bladder in a cat with LUTD.
Multiple bright echoes with acoustic shadowing of urinary
bladder indicative of cystic calculi.
52
11 Ultrasonographic examination of urinary bladder in a cat.
Evidence of diffuse thickening of urinary bladder wall and
sandy urine indicative of cystitis.
53
12 Electrocardiogram of cat with severe hyperkalemia associated
with associated with obstructive lower urinary tract disease.
Notice increased time interval between QRS complex and
severe bradycardia (<50 bpm).
53
55
LIST OF APPENDICES
APPENDIX
NO.
TITLE PAGE NO.
1 Proforma for case record 132
2 Formulae for calculating sensitivity,
specificity, accuracy and predictive values of
different diagnostic tests for feline lower
urinary tract disease
135
3 Complete research analysis record of data
presented
137
56
CHAPTER 1
INTRODUCTION
Idiopathetic Feline Lower Urinary Tract Disease (iFULTD) has proven to be an
important clinical disorder related to feline and presents itself a major veterinary medical
problem. Previously, it has been known as urolithiasis- cystitis- urethritis (Holzworth 1963),
feline urologic syndrome (FUS), (urolithiasis syndrome (Fisher 1955), Osbaldiston and
Taussig 1970) and feline lower urinary tract disease (FLUTD), (Osborne et al. 1984). These
terms are interchangeably used in the ut infra description of the disease. Feline urologic
syndrome is a blanket term signs of anuria, dysuria hematuria, and increased frequency,
either singly or in combination (Osborne 1975). Moreover, feline urolithiasis is commonly
referred to as the feline urologic syndrome and urethral obstruction occurs when sandy
gravel, blood clots, small stones, cellular debris/mucus, or combination of these become
lodged in the urethra (Fabricant 1977).
Feline urinary tract disease has been classified as obstructive and non-obstructive.
Non-obstructive FLUTD is characterized clinically by hematuria, dysuria (stranguria),
pollakiuria, vocalization and periuria. Male cats frequently lick external genitalia, simulating
constipation. In obstructive disease, mucoid-crystal plug is lodged in the tapering distal
urethera. Untreated obstructive cases die of post-renal azotemia (Norsworthy et al. 1998).
Research during the last 3 decades has revealed that FLUTD may result from a
variety of different causes including crystalluria, uroliths, urethral plugs, urinary tract
infections (viral, bacterial, fungal, parasitic), congenital or acquired anatomic abnormalities
of bladder and urethera and iatrogenic or idiopathic causes (Kalkstrein et al. 1999).
57
Many risk factors like age, breed, sex, neutering, diets, feeding frequency, excessive
weight, decreased water consumption, season and indoor life style have been identified for
FLUTD, some of which appears to be synergistic (Osborne 1989; Willeberg 1981).
Irrespective to the cause of urethral obstruction, predictable biochemical and clinical
abnormalities (less fluid intake may lead to dehydration, electrolyte imbalance may lead to
hypercalcemia, hyperphosphatemia, acid-base imbalance may lead to metabolic acidosis,
and retention of metabolic waste may lead to accumulation of creatinine, urea, and other
protein catabolites) subsequently develop (Osborne et al. 1984). Urethral plugs composed
of large quantity of matrix and variable quantities of minerals are extremely uncommon in
females (if they occur). Till yet its phenomenon is unknown. Moreover, there is an
alternative explanation related to sex differences in periurethral glandular tissue and these
anatomical differences led to the higher incidence of obstruction males compared to
females (Osborne et al. 1984).
The incidence of signs of FLUTD in domestic cat in United States and Great Britain
has been reported to be approximately 0.5 – 1% per year (Osborne et al. 2000). Buffington
and Chew (1997) cited that 9.1% of feline patients presented to Japanese veterinarians had
FLUTD. The hospital data of Department of Clinical Medicine and Surgery, University of
Agriculture Faisalabad and Pet Center, University of Veterinary and Animal Sciences, Lahore
indicates that the condition is present among cats in Pakistan but due to poor cognizance of
practicing veterinarians, it has gone unreported thus far (unpublished data). The rates of
urolith occurrence have been observed in bladder more than the urethra. Uroliths with less
than 70% of one mineral component and uroliths with a nucleus and a shell of different
mineral composition were called mixed stones (Osborne et al. 1983).
58
Epidemiology of this disease is concerned with the description and analysis of
disease occurrence. Moreover, valid frequency estimates can only be obtained through
formal procedures of collecting and analyzing data on cases of FUS and the cat population
from which they originated (Osborne et al. 1984). Social setup in Pakistan is invariably in
contrast to those of developed countries. Human-animal bond in our society is not as strong
as in developed countries. Except few owners vigilant enough to properly take care of their
pets, most pets are managed by different family members or sometimes pets are at their
own most of the time. Dietary management practices are unknown intervention to our
veterinarians as well as to pet owners. No strict dietary plans are followed, and pets are
often fed table-scraps, other owner’s recipes, home cooked food, raw food including
chicken heads and giblets. Preformed cat foods have come to the markets but they are
being used haphazardly on owner’s choice without knowing the formula and their pet’s daily
requirements, both in health and disease.
No infrastructure is available for the proper veterinary services to the pet holders.
Due to this fact, most of the time pets are treated by owner themselves, other owners
suggested recipes and professional quakes in veterinary profession. Feline Urinary Tract
Disease seems to be common in Pakistan as per experience of clinical practice but virtually
no study has been done here in Pakistan over this important disease of feline. Keeping the
above scenario in view, the present study has therefore, been planned on the following
objectives:
1. Epidemiological data analysis (including host determinants as the age, breed and
sex; if any) with the occurrence of iFLUTD and conceptualize the control measures
by analyzing epidemiological data generated by the short epidemiological study,
59
2. Evaluation of serum-cortisol levels as a diagnostic tool for the detection of
interstitial cystitis (IC) development among cats affected with LUTD and its
comparison with other diagnostic tools (viz., urinalysis, radiography and
ultrasonography),
3. To study the effect of food in the development of interstitial cystitis among cats and
4. To study the effect of Pentosan polysulfate sodium and detressor muscle relaxant
(Tablet, uricon) with and without Vitamin C in the treatment of IC.
60
CHAPTER 2
REVIEW OF LITERATURE
Kirk (1925) noted obstruction as the most important cause of idiopathic feline Lower
Urinary Tract Disease (ifLUTD) especially in case of tom (male) cats. While less frequent
causes noticed were urethral calculi. Furthermore, he described the term “retention of
urine” as very common condition found in case of iFLUTD in cats. He also noted that the
major cause of this problem was urethral obstruction (caused by a material) and other
causes noticed were cystic or urethral calculi. Osbaldiston and Taussig (1970) used the term
‘feline urological syndrome’ (FUS) for the first time and described the syndrome as a
combination of signs like dysuria, urethral obstruction, urolithiasis and hematuria. Both the
authors concluded that FUS is not a single disease entity however it includes a group of
different urological problems. Later on, Osborne and co-workers (1984) discussed FUS as a
synonym for lower urinary tract disorders (LUTD) among felines. Markwell and Buffington
(1994) proposed that the cluster of signs of lower urinary tract disease without any specific
diagnosis must be listed under the appropriate descriptive term of ‘idiopathic lower urinary
tract disease (iLUTD)’. Norsworthy (1998) associated the term feline lower urinary tract
disease (FLUTD) with that of interstitial cystitis (IC) in women. Roger and scientists (2005)
also supplemented previous studies by describing that most of the felines affected with
lower urinary tract disease either have iLUTD or IC, but apart from these two conditions
there may be urolithiasis, any kind of bacterial infection, neoplasia, anatomic
malformations, behavioral/neurologic disorders which were more uncommonly than IC.
Blount (1931) described 7 different types of urinary calculi and among all of these
‘triple phosphates’ he noted, the majority of them was deposited in the alkaline urine. Milks
61
(1935) noticed only one urethral calculus obtained from a feline and proposed that these
calculus are fairly common among felines. Jackson (1972) later on described the
epidemiological data with the higher incidence rate as around 10% among the feline
patients he studied. Elcock (1981) undertook epidemiological studies in USA in which he
estimated the incidence of FUS around 1 percent among the feline patients under study.
Lawler and co-workers (1985) illustrated similar trend in incidence rates of obstructive and
non-obstructive lower urinary tract disease cases as 0.34 to 0.55, 0.6 to 0.64% per year,
respectively. Osborne and colleagues (1989) reported the incidence rate of FLUTD both in
the United States as well as Great Britain as approximately 0.5 – 1% per year. Kruger and co-
workers (1991) conducted a study based on the referral institution of felines in which the
authors concluded that about 55 to 69 % of the felines affected with the Feline Interstitial
Cystitis (FIC). Patronek and his colleagues (1996) studied and declared that approximately 4
million (annually) felines were sent to the animal shelters due to unacceptable highly
aggressive behavior of felines affected with this condition. Buffington and co-workers (1997)
conducted a study on the feline patients presented with the non-obstructive urinary tract
disease attending at the Veterinary Medical Teaching Hospitals (VMTH) and declared that 13
to 28 percent of the cats were affected with the problem of urolithiasis. Buffington and
Chew, (1997) reported that about 9.1% of the feline patients attended were affected with
the FLUTD attending at Japanese veterinary hospitals. Lund and co-workers (1999)
estimated the prevalence of feline LUTD in primary care practice in the US as approximately
1.5%. Baines and co-workers (2001) attended cases regarding FLUTD and determined that
majority (55.69%) of them were related to idiopathic type and exact cause of this condition
is still not known and have been under discussion from many decades especially for the
inflammation heading towards FLUTD.
62
Risk Factors
Willeberg (1984) concluded that felines between the age of 2 to 6 years are more
prone to this disease condition as compared to those which are less than 1 year or greater
than 10 years of age. He also identified many risk factors that were strongly associated with
FUS. Furthermore, he declared that urethral obstruction frequency is much higher in
castrated male cats as compared to intact male cats. Sternberg and his colleagues (1992)
suggested that apart from many risk factors stress is also an important factor that
participates in worsening the clinical signs of feline LUTD which include any kind of stress
even the stress built up as a result of an earthquake. Later on, Jones and co-workers studied
the weather changes as stress factors participating in the cause of FLUTD and approved
stress as an important factor leading to FLUTD. Buffington and his colleagues (1996)
associated the dietary changes as major factor strongly related to the enhancement of
recurrent episodes of LUTD in feline patients. Markwell and his colleagues (1998) concluded
from their study that diet plays a major contribution in the etiology, management, control
or prevention of recurrence of idiopathic lower urinary tract disease (iLUTD). Laubel and co-
workers (2004) recommended regular risk factors involving and their proper evaluation
along with risk monitoring throughout stone therapy that measures to confirm reduction of
recurrence of crystal formation again and again. Bartges and Kirk (2006) investigated that
lower urinary tract disease (LUTD) commonly found among cats which is most commonly
associated with crystal urea. In all such cases, most important remedy is based on dietary
modifications that proved to be beneficial in managing a part of these diseases. Change in
dietary formulations may positively result in decreasing urinary concentrations of crystal
producing compounds, increasing the urinary concentrations for crystallogenic inhibitors
(which can control crystal production) and diluting urine composition. Markwell and co-
63
workers (2006) compared and evaluated recurrence rate of clinical signs of ifLUTD with
cystitis that were fed based on the dry/canned formulations (commercial diet; designed to
result in an acidic urine). They also suggested that feeding commercial canned diets acidifies
urine which may help in reducing the big proportion of cats (affected with idiopathic cystitis;
IC) that suffer from signs of LUTD within a 12-month period again and again. Forrester
(2008) suggested many different therapies for management of cats affected with LUTD.
Diets with more moisture contents along with other methods to increase water intake were
suggested to cope with FIC, urethral plugs and urolithiasis. Gerber and his colleagues (2008)
documented the course of urethral obstruction among 45 cats. Recurrent obstruction (n =
14; 36%) was most common reason for euthanasia and was performed in 8 (21%) out of 39
feline patients.
64
Etiologic Agents
Rich and Kirk (1969) suggested that prevalence of crystals from urine samples of
normal cats were different from that collected from cat affected with LUTD. Schechter
(1970) further conducted a study on crystalluria and supplemented the previous data that
magnitudes of urine crystals were different in both the normal and lower urinary tract
disease affected feline. Lewis and Morris (1984) studied the crystalluria as an important
factor of cystitis and urethritis in felines especially the struvite crystalluria. According to
authors FLUTD may be the result of other factors like that of urethral plug, uroliths or any
kind of bacterial infection. Moreover, Kruger and his colleagues (1991) also conducted a
study on the crystalline urine and proved that the mineral composition of the urine crystals
collected from healthy felines were distinguishable from those collected from diseased one
(affected with FLUTD). Osborne et al. (1996a) narrated that lower urinary tract disorders in
both sex of cats may be due to a variety of fundamentally different causes. The respective
term used as ‘Feline Urologic Syndrome’ (FUS) should be abandoned where it is not
considered as correct/appropriate term for expressing this disease and substituted with
descriptive etio-pathogenic terms whenever needed. If the underlying cause is not
known/confirm, the term Idiopathic lower urinary tract disease could be used or
recommended instead. Buffington and his colleagues (1997) worked on the urine culture
and resulted that urine cultures executed for aerobic bacteria were consistently negative in
felines submitted with the complaint of LUTD. Bartges and his colleagues (2004c) involved 3
kinds of feeding patterns. Statistically significant difference (in urine saturation) with CaOx
between 3 diets with the highest saturation (based on the water contents within diet)
occurring in cats consuming the acidifying diet and the lowest saturation (based on the
water contents within diet) occurring in cats consuming the alkalinizing diet. Urine
65
saturation (based on the water contents within diet) with struvite was not found different
between all groups under study. The diet was not observed to significantly influence bone
mineral content or density. From the present study, it was deduced that to induce urine
under saturation CaOx was obtained by using that diet. All this was influenced by urinary Ca,
Ox, Mg and P excretion and thus by inducing an alkaline urine pH. Secondly, feeding an
alkalinizing diet was not in association with that of increased urine saturation with struvite
hence urine pH is the only one factor influencing directly or indirectly on this risk. Last but
not the least bone demineralization was not apparent/observed in these healthy cats.
Walker and his colleagues (2008) stated that hypertension (HT) is one of most common
problems in cats with older age affected with chronic kidney disease (CKD). Purpose of this
study was to check the hypothesis that reduced conversion of cortisol to cortisone leads to
the development of HT in cats affected with CKD and idiopathic hypertension (iHT).
Seawright et al. (2008) reported that FIC is one of the most common causes related to
medical ailment because of elimination change in feline, and thus it proved to be an
important differential while working as veterinarian or as owner with cats suffered from
inappropriate elimination. Thus, specific stress-generating-events lead to such outbreaks
and controlling such factors may reduce/prevent FIC by implementation of behavior therapy
protocol. Ellis (2009) elucidated the housing patterns and their effect on the cats affected
with LUTD. All the client owners have the responsibility of taking care of their pets and thus
need to allow their pets to exhibit normal behavior patterns
Urinary tract infections
Viruses
66
Fabricant (1977, 1984) worked on the agent similar to virus directly linked with the
spontaneous feline LUTD. Osborne and his colleagues (1989, 1992) observed that there are
some virus-like particles having morphological distinctiveness similar to those of calici
viruses and found in the form of a combination with crystalline matrix. They also suggested
that the urethral plug that is mainly obtained from tom (male) cats affected with
spontaneous urethral obstruction is remarkable. Kruger and Osborne (1990) supplemented
the previous work done on the causative agent of FLUTD and suggested viruses as one of
the causative agents taking part in the etiology as well as pathogenesis of spontaneous
feline LUTD. Kruger and co-workers (1991) conducted a prospective study of 143 cats
(included both the gender) at the University of Minnesota that was actually designed in
order to determine exact causative agent leading to spontaneous feline LUTD and
succeeded in determining specific etiology only in 77 (53%) out of 143 felines. Osborne and
his co-workers (1992) further worked on viruses and incriminated viruses as important
causative agents taking part in the aggravation of naturally occurring feline lower urinary
tract disease. Kruger and his co-workers (1996) suggested that exact etiological agents of
the conditions like hematuria, dysuria, and urethral obstruction are still under great
discussion and not known however viruses could be an important agent taking part in the
cause of idiopathic form of LUTD. They also supported the fact that gamma herpesvirus,
calici virus, and retrovirus were isolated from urine and tissue samples of felines affected
with LUTD. Barsanti et al. (1996) checked out prevalence of seropositivity for feline
immunodeficiency virus (FIV). To this, they compared diseased group based on 41 cats (with
signs of lower urinary tract disease) to another group of healthy cats (n = 41) having no
distant or past history of disease. The most common cause observed during the whole study
67
of lower urinary tract signs was found to be idiopathic (without no particular cause) in
nature.
Bacteria
Barsanti and his colleagues (1982) conducted a study in felines and approved that
bacterial Urinary Tract Infections (UTI) were directly or indirectly linked with signs of LUTD in
1 to 3 percent of felines. Lee and collaborators (1979) conducted a study and brought the
new concept that high rate of bacterial UTIs in felines are directly associated with the
felines’ innate ability to produce greatly concentrated acid urine (with large quantity of urea
in it). Gregory and Vasseru (1983) performed an experiment and concluded that presence of
large quantity of Tamm-Horsfall mucoprotein in urine of cat may help in minimizing
bacterial UTI. Osborne and his partners (1989, 1991) performed an experiment and
concluded that after the use of the UTIs increase up to 50%, while the use of technique like
perineal urethrostomy, the prevalence rate may exceed up to the level of 20 percent.
Osborne with his colleagues (1992) conducted a study on the bacterial UTIs. According to
the authors bacteria had often been detected in crystalline-matrix of plugs (in male cats)
and thus its proper identification along with correction in the form of proper antibacterial
therapy are badly needed for long-term eradication of microbes taking effective role in
aggravation of FLUTD. To this end, the urine culture should be performed 3 to 5 days after
initiation of therapy in order to confirm sterilization of urine. Eggertsdottir and his
colleagues (2007) conducted a survey at the Norwegian School of Veterinary Science and
concluded that bacteriuria may be under diagnosed in cats living in Norway (showing signs
of FLUTD) where feline lower urinary tract disease (fLUTD) was found to be one of the most
common diagnoses found in case of feline patients.
68
Mycoplasmas and Ureaplasmas
Tully (1983) conducted an in-vitro study using synthetic urine and later on suggested
that the ureaplasmas have ability to survive in the osmotic conditions naturally present in
urine of normal cats as compared to mycoplasmas that lack that ability to survive in such
condition. Kruger and his workers (1991) were determined to isolate mycoplasmas and
ureaplasmas from the urine of more than 143 felines affected with spontaneous form of
LUTD but they failed to accomplish the set target. Brown and his colleagues (1991)
investigated that the lack of recovery of mycoplasmas and ureaplasmas from feline urine
samples might be part of unsuitable culture factors or any kind of inhibitory host factors
leading to inhibition of their recovery. Fulton and Walter (1992) worked on the previous
study and investigated similar report regarding isolation of mycoplasma and ureaplasma
from feline urine. They also concluded that there are some host factors also taking part in
the limitation of their growth in vitro like that of high ammonia concentrations, high urine
pH, osmolality, and inhibitory antibiotics.
69
Fungi
Wooley and Blue (1976) worked on the fungal infections affecting lower urinary
tract of the cats. Later on, Finco and his colleagues (1985) conducted the similar kind of
study and concluded that fungal UTIs may enhance the condition like FLUTD. Fulton and
Walker, (1992) studied the fungal infections leading to LUTD in felines and proved that those
infections cannot be ignored while making the differential of the FLUTD. They also
concluded from their study that those cats having fungal UTIs previously had had history of
therapy against FLUTD. Lulich and Osborne, (1992) determined that the fungal UTIs both in
the humans as well as canines and felines came from either the prolonged use of antibiotic
or glucocorticoid administration or transurethral catheters or acid-urea or some kind of
systemic disorders that take part in compromising the host urinary defensive system.
Parasites
Brown and Prestwood (1986) studied the association between the presence of
parasites and FLUTD and found that parasites rarely take part as causative agent leading to
FLUTD. However, the nematode Capillaria felis cati was one of the only parasites that was
found in association with the signs of FLUTD and such kind of infections appeared as
asymptomatic might be due to their low numbers as well as their superficial attachment to
the mucosal wall of the bladder.
Matix-Crystalline Urethral Plugs
Bartges et al. (2004a) conversed that urolithiasis is one of the most common
diseases of cats. During previous study conducted in 1982, about 88% of uroliths extracted
and completely analyzed from felines were composed of struvite and 3% were composed of
70
CaOx. On the other hand, in study conducted in the year 2002 about 40% of uroliths were
composed of struvite and 50% were composed of CaOx. While, about 95% of nephroliths
found in cats are composed of Ca salts. Osborne and co-workers (2004) analyzed 46,755
feline uroliths that were submitted to the Minnesota Urolith Center and observed that
about 64 out of them were composed of xanthine. Chauvet and Ryall, (2004) scrutinized
intra-crystalline proteins confined/embeded within calcium oxalate (CaOx) crystals obtained
from urine samples collected from humans may help to prevent stone formation by
enhancing/taking part in lysosomal devastation of crystals internalized by renal epithelial
cells. Vega and his other members of the staff (2004) revealed that attachment of urinary
crystals with the tubular cells of kidney might be a serious event taking part in the kidney
stone formation. Tsujikawa and his colleagues (2004) revealed that adherence of newly
formed crystals to the epithelial cells of kidney seems to be a crucial step in the
development/appearance of kidney stones. Chauvet and Ryall (2004) observed that intra-
crystalline proteins might be responsible for lysosomal destruction of crystals internalized by
renal epithelial cells. Tikoo et al. (2004) resulted that crystal retention in kidney is the most
important step in CaOx stone formation. Among majority of people body do not form stones
in spite of crystaluria, which indicates that kidney epithelial cells are able to handle
crystalline waste produced. Ryall et al. (2004) resolved whether Tamm-Horsfall glycoprotein
(THG) unites permanently to the CaOx crystal (at its surface) and get trapped within the
mineral bulk during its growth. The THG does not unite permanently to the CaOx crystal
surface that is related to its fragile reservation/inhibition of CaOx crystal growth within urine
along with inorganic media. The THG has got potential power to inhibit aggregation which
results from stringent obstruction preventing inter-crystal union and solidity. Chow et al.
71
(2004) examined that with the exception for rare matrix stones CaOx are primary
crystallines found as urinary calculi followed by CaPO4 (found to be predominant).
Diagnosis
Cornellus and colleagues (1965) worked on the Tamm-Horsfall mucoprotein in
humans. Later on, Grant and co-workers (1973) identified Tamm-Horsfall mucoprotein in
the ovine uroliths and that mucoprotein was supposed to be a local host defense
mechanism against viral and bacterial UTIs. Jones and his colleagues (1989) worked on the
increasing concentration of Tamm-Horsfall mucoprotein found in feline urine mainly
affected with LUTD. They supported the previous hypothesis that was made on the basis of
mucoprotein as a major component of plug matrix. Osborne and his colleagues (1989)
conducted a double contrast cystography and revealed the presence of uroliths in 22
percent of the feline patients attended and the uroliths were detected by the help of survey
radiography. Osborne and co-workers (1990) conducted a study on 30 feline patients
affected with uro-cystoliths and among these patients in only 3 cats they detected all the
stone with the help of method of palpation. Kruger and his colleagues (1991) conducted a
study at the University of Minnesota Veterinary Medical Teaching Hospital (VMTH) during
the year 1983 to 1985 based on 141 cases of felines affected with LUTD and explored that
23 percent of the felines admitted had struvite calculi issue. Kruger and his colleagues
(1991) conducted a study regarding the most common cause of obstructive form of LUTD
and determined that urethral plugs re mainly taking part in obstruction in male felines.
Buffington and co-workers (1992) proved in a study that struvite urolithiasis is taking major
part in the FLUTD. Buffingon and Chew (1993, 1995) identified in their study that increased
number of mast cells were found within the sub-mucosa of the feline bladder of felines
72
affected with idiopathic form of LUTD as compared to the normal ones. Sant and
Theoharides (1994) hypothesized that products of activated mast cells could be responsible
for inflammation, fibrosis, pain, vasodilation, and smooth muscle contraction associated
with feline idiopathic LUTD. El-Mansoury and co-workers (1994) found from their study that
in human IC patient’s urine, histamines and its metabolites have been found in higher
concentrations. Buffington and Chew (1995) worked on the metabolites of the feline urine
affected with FLUTD and found that histamines and metabolites were found from
cystoscopic effluent of felines affected with iLUTD. Roger and his co-workers (2005) cited
that the feline patients when evaluated with fiberoptic urethroscopy, plugs were identified
in approximately 30% of the felines in a preliminary study conducted at The Ohio State
University (USA) and also found that other potential causes include urolithiasis, UTIs,
urethral spasm and neoplasia. The male cats are greatly predisposed to urethral obstruction
as compared with female cats due to extremely narrow penile urethra. Wallius and Tidholm,
(2008) discussed and suggested that feline IC has been diagnosed properly by the help of
performing histopathology of bladder wall biopsies that were taken from cats affected with
LUTD. Polzin and Jenaj (1979) found in their study that any bacterial isolation from urine
sediment is suggestive but not conclusive evidence of bacterial UTI. Kruger and his
colleagues (1991) during their study determined that the concentrated urine is a major and
consistent clinical feature of felines affected with non-obstructive idiopathic LUTD. Ratliffe
and co-workers (1994) approved in the study that high concentrations of either normal or
abnormal components within urine might prove to be toxic to urinary bladder tissue in
human patients affected with interstitial cystitis. Lulich et al. (1996) presented a case study
showing typical signs as well as natural progression of iFLUTD. Lees (1996) determined in his
study that quantitative urine cultures proved to solve the problems regarding the
73
interpretation of urine sediment findings and provided the most reliable means of
confirming and localizing bacterial UTIs in felines affected with LUTD. Johnson and co-
workers (1996) conducted survey radiographs in their study and concluded that such
diagnostic tools are proved to be essential for the diagnosis urethroliths, any kind of foreign
material, crystalline-matrix, urethral plugs and anyother concurrent abnormality involving
kidney and ureter. They proved that the laterally viewed radiography is more informative
than the ventro-dorsal for identification of radiopaque uroliths in the bladder or urethra.
Voros and colleagues (1997) worked on the sonography technique in their study and proved
it as a useful technique for diagnosing urinary bladder calculi and plugs even when they
were radiolucent as well as also helpful for making proper differential regarding LUTD. They
also suggested that ultrasonography is a valuable diagnostic tool but radiography still needs
some attention for proper diagnosis. Buffington and co-workers (1997) determined in a
urinalysis study that the urinalysis of feline urine sample collected from cat affected with
LUTD is typically characterized by hematuria without association with pyuria or bacterial
UTI. However, urinalysis results may be normal in some felines affected with LUTD. Scrivani
and his colleagues (1997) described the results related to retrograde urethrography among
felines affected with idiopathic non-obstructive LUTD in order to review the normal
anatomy of the feline urethra and also to supplement the relation between anatomies
observed radiographically to that of its pathogenesis along with diagnosis of iFLUTD. Scrivani
et al. (1998) conducted retrospective study and investigated the double-contrast
cystography in cats affected with idiopathic cystitis (IC). Results of present study suggested
that a large number of cats affected with IC do not show cystographic abnormalities.
Robertson (2004) explored disagreement right from years to calculate pH value in 24 hourly
collected urine samples from urolithiasis cases/patients. Hence, it is concluded that urine pH
74
may prove to be a good tool in the diagnosis of stone-formers and non-stone-formers.
Forrester (2004) investigated that hematuria is one of the major signs indicating the
presence of urogenital disease both in case of dogs and cats. In case of failure in evaluation
of source/cause of hematuria, exploratory celiotomy should be considered in mind. Gerber
et al. (2005) investigated major clinical signs and source of cause leading to feline lower
urinary tract disease (fLUTD) in 77 cats. Severity/extent of pain was found less common in
cats affected with uroliths, while haematuria was most commonly seen in cats with urinary
tract infection. Out of 77, in 44 cats (57%), no particular cause was found for the disease and
they were classified into separate group (having idiopathic type of LUTD). Lee and Kenneth
(2006) evaluated historical and physical parameters as good predictors of hyperkalemia in
male cats affected with urethral obstruction. In conclusion, rectal temperature and heart
rate were found to be the best parameters for predicting hyperkalemia in this population of
cats. Buffington et al. (2006) assessed client-reported recurrence of LUTD signs and other
signs of abnormalities in cats with IC after the institution of multimodal environmental
modification (MEMO). MEMO is an effective adjunctive treatment for cats kept exclusively
indoor showing signs of lower urinary tract and should be followed up with future
controlled-clinical trials.
Treatment
Schechter (1970) in his study prescribed antibiotics use in order to pragmatically
treat idiopathic LUTD, though bacterial UTIs are not so common among young to middle-
aged felines affected with LUTD. Blaivas and colleagues (1980) conducted a study on
detressormuscle contractions in LUTD and determined that the anticholinergic agent
(propantheline) reduces the frequency of uncontrolled detrressor muscles contractions.
75
Chew and colleagues (1986) suggested the use of smooth muscle anti-spasmodics as a
symptomatic therapy for LUTD. Parsons and Mulholland (1987) worked on the efficacy of
PPS. PPS was found to be statistically significant on pain management (44% of patients in
PPS treated and 15% in the placebo group). Ross (1990) recommended in his study anti-
cholinergic agents for the management of pollakiuria related with the idiopathic LUTD. Ross
(1990) conducted a study regarding the therapeutics againft FLUTD and used Dimethyl
sulfoxide (DMSO) in felines mainly affected with idiopathic form of LUTD based on the
reports of efficacy in humans affected with IC and the efficacy of intra-vesicular instillation
of DMSO in felines affected with chronic LUTD showed elimination of clinical signs of LUTD.
Parsons and co-workers (1990) carried out a study regarding therapy of felines affected with
LUTD and proved that the urothelial glycosaminoglycans (GAGs) reduces the superficial
adherence of microorganisms and crystals to the bladder lining (urothelium). Moreover,
they determined that GAGs also minimize the transport of urine proteins and other solutes
from the bladder lumen into the surrounding tissues. Mulholland and associates (1990)
investigated the response of PPS therapy. To this end, they randomized total of 110 patients
and treated with PPS either @ 100 mg/three times a day or placebo for duration of three
months. Statistically no significant change in urinary ailment was found in either treatment
groups. Moreover, the effect on pain was statistically same in both the groups under study.
Thus PPS showed benefit in patient’s self evaluation for the parameters pain and urgency
but failed to affect the urinary ailments with respect to statistics. Marks and his co-workers
(1993) in a study recommended skeletal muscle antispasmodics like, dantrolene, diazepam
for the symptomatic management of urethra-spasm associated with idiopathic form of
FLUTD. Buffington (1994) determined in his study that the long-term use of acidifiers may
lead to hypokalemia, renal dysfunction and thus the end would be in the form of Ca-oxalate
76
urolithiasis problem. Osborne and colleagues (1995) conducted a study and suggested that
the over acidification with the use of acidifiers leading to metabolic acidosis is almost
certainly to occur in felines mainly consuming acidifying diets. Mandelker (1995) conducted
a study and advocated that the amitriptyline has been sponsored for the symptomatic
therapeutic use for FLUTD and thus amitriptyline has also gained popularity as an agent for
symptomatic therapy for feline iLUTD. Fitzgerald (1996) conducted study on the use of
amitriptyline for FLUTD and determined that sedation, rough hair coat, obesity, urine
retention, neutropenia and thrombocytopenia have been the side effects observed in
felines treated with amitriptyline. Osborne and his colleagues (1996) conducted an
experimental trial based on the therapy of FLUTD and proved that prednisolone used at the
recommended doses was of no advantage in reducing the severity as well as duration of
clinical signs in felines affected with LUTD. Osborne and his colleagues (1996b) performed
an experiment in the form of a double-blind clinical study in order to evaluate the effect of
prednisolone as treatment therapy for ifLUTD. Insignificant difference was observed
regarding response in prednisolone-treated and placebo-treated cats affected with iLUTD.
Kruger and colleagues (1996) studied that persistent effective therapy and prevention of
nonobstructive ifLUTD in male and female cats remains an enigma because clinical signs
related with this form are frequently self-limiting. Chew and his co-workers (1998) evaluated
the safety, efficiency and effectiveness of amitriptyline hydrochloride against the treatment
of recurrent type of idiopathic cystitis (IC) among 15 cats. Amitriptyline treatment proved to
be successful in decreasing clinical signs of severity in recurrent IC (n = 9; out of 15 cats in
total). However, somnolence along with weight gain, decreased grooming as well as
transient cystic calculi were observed during treatment study among some of the cats.
Baines and co-workers (2001) during their study investigated the indications for long-term
77
conclusion of Prepubic Urethrostomy (PPU) in felines. To this end, they collected a data of
16 cats which shows that all cats (n = 16) recovered from the medical ailments. The PPU
seemed to be a simple procedure that should be considered as a safe technique in case of
obstructive disease of the pelvic urethra. Andersson and Hedlund (2002) investigated that
voiding may be initiated in case of myogenic activity of urothelium, distention of the
detrusor, and signals from the urothelium. Within bladder a plexus is formed by the
combination of afferent nerves. This factor of activation is not solely responsible for part of
the bladder contractions, but also taking part in the formation of different symptoms
leading to overactive bladder. It could be a new as well as important target for therapeutic
interventions. Sadhukhan et al. (2002) proposed that PPS might be responsible for the
inhibition of unspecified stimulants leading responsible for bladder inflammation and hence
directly or indirectly helps/involves in the reduction of urothelial responses to inflammatory
stimuli. Kraijer and co-workers (2003) studied the effects of amitriptyline as compared with
that of a placebo in feline suffering from iFLUTD. The therapy is no more beneficial as a
short-term therapy where the therapeutic outcome depend on tangential effects of the
drug. However, long-term effects may be considered from 4 weeks or more after the
beginning of therapy. This area of research need further investigated. Kruger et al. (2003)
determined the efficacy of administration of short-term use of amitriptyline administration
in the treatment of acute/nonobstructive idiopathic LUTD among cats. Statistically, no
apparent differences in likelihood/rate of recovery from pollakiuria/hematuria between
groups have been observed. Gunn-Moorea and Shenoya (2004) compared oral glucosamine
therapy with that of placebo for the management of cats affected with IC in a randomised
double-blinded placebo controlled study. Davis and his colleagues (2008) proposed a pilot
study based on the therapy based on the PPS against PBS/IC. About 80% of pain along with
78
urinary urgency and nocturia was decreased and excellent response was reported among
71% of the human patients. Wallius, and Tidholm, (2008) assessed the efficacy of pentosan
polysulfate sodium (PPS) in cats. From the present study the authors are still doubtful
regarding the authenticity of PPS efficacy in population of cats affected with LUTD (having
continuous/frequently recurring clinical signs). However, it may be further elucidated in
approaching double-blind, randomised and placebo-controlled trials including only such kind
of population of cats having recurrence rate of LUTD clinical signs.
Serum Cortisol
Cauvin and co-workers (2003) investigated the Corticoid:Creatinine Ratio (UCCR)
among 31healthy client-owned cats. Statistically insignificant relationship was observed
between UCCR and age, breed and sex. While, statistically significant augmentation in the
UCCR was observed between both (at home and hospitalized) of the first urine sample
collected. The normal range for feline UCCR was established for the chemiluminescent
immunoassay (as used in this study). McCobb et al. (2005) determined stress intensity in
felines by keeping cats in traditional as well as enriched shelter environments through
behavioral assessment and urine cortisol-to-creatinine ratios. To this end, a cross-sectional
observational study was conducted in which 120 cats were observed in 4 Boston-area
animal shelters. cat stress score cannot be used as a useful instrument for measuring stress
level among cats because it proved to be unable in order to identify cats with faked sleep
and high stress levels. The UCCR (Urine cortisol-tocreatinine ratio) can be monitored to
noninvasively assess stress levels in confined cats. Drobatz and his colleagues (2005)
inspected parathyroid hormone (PTH) and 25-OH vitamin D3in serum concentrations of cats
affected with urethral obstruction. In order to measure serum PTH and 25-OH vitamin D3
79
concentrations, a prospective single cohort study was conducted at the University affiliated
veterinary teaching hospital. Statistically no significant relationship was found between 25-
OH vitamin D3 including those of any other measured variables of present study.
80
CHAPTER 3
MATERIALS AND METHODS
Keeping in view the main objectives, present study was conducted regarding
idiopathic Feline Lower Urinary Tract Disease (iFLUTD) in client-owned domesticated felines
(n = 502) belonging to different age groups for a period of two years (2008-2010) in different
clinics (Veterinary Medical Teaching Hospitals as well as private clinics) of Lahore, Faisalabad
and Islamabad (Pakistan) in the form of two phases. Phase I included the epidemiological
data analysis as well as efficiency of different diagnostic tools used for the diagnosis of
idiopathic Feline Lower Urinary Tract Disease (iFLUTD), while Phase II included therapeutic
trial. Detailed procedures along with the methodologies adopted are mentioned as under.
Phase I.
1. Epidemiological Investigations:
Study animals and settings
Total target of more than five hundred domesticated felines of either sex and of any
age, breed, etc showing signs of iFLUTD as per Buffington (1994) were examined for the
period of two years. Felines having previous history of treatment for iFLUTD were also
included in the present study. Complete historical background was collected based on a
detailed structured interview of the owners that was noted on a predesigned proforma
(Appendix) for further investigation of different factors affecting/taking part in causing
iFLUTD. All data regarding the epidemiology of this disease was collected on monthly bases
from Lahore, Faisalabad, and Islamabad (Pakistan) which involved pet hospitals belonging to
the Veterinary Medical Teaching Hospital (VMTH) as well as data from private clinics.
81
Descriptive epidemiology
Active disease surveillance
Active disease surveillance was carried out to determine the incidence of causes of
iFLUTD in client-owned domesticated felines belonging to different age groups for a period
of two years (2008-2010) in different clinics (VMTH as well as private clinics) of Lahore,
Faisalabad and Islamabad (Pakistan).
Morbidity rate:
The rate of disease (iFLUTD) in different clinics (VMTH as well as private clinics) of
Lahore, Faisalabad and Islamabad Cities was also studied.
Mortality rate:
The rate of death due to idiopathic Feline Lower Urinary Tract Disease (iFLUTD) in
different clinics (VMTH as well as private clinics) of Lahore, Faisalabad and Islamabad Cities
was also calculated accordingly.
Passive disease surveillance
The passive disease surveillance of different veterinary hospitals of respective cities
(Lahore, Faisalabad and Islamabad) regarding iFLUTD in different clinics (VMTH as well as
private clinics) was also conducted accordingly.
Prevalence
Prevalence study (referred to the amount of disease in each clinic for a period of
two years) without any criterion regarding past distant history or present distant history (old
82
and new cases) was conducted accordingly. The particular formula for the prevalence
calculation is mentioned below as
No. of individuals having a disease at a particular point in time
P = -------------------------------------------------------------------------------
No. of individuals in a population at risk at that point in time
Analytical Epidemiology
Seasonal influence – In order to observe the influence of season on the occurrence of
idiopathic Feline Lower Urinary Tract Disease (iFLUTD) among domesticated felines,
metrological data was also studied. Season-based data was made on the basis of four
seasons as following break up such that winter (November – February), spring (March -
April), summer (May-August), autumn (September - October). Complete data collected was
then related with the different metrological data i.e., temperature, rainfall, humidity of
Lahore, Faisalabad, and Islamabad cities (Pakistan) was calculated accordingly.
Risk factors and control measures – Different disease determinant risk factors including sex,
breed, management/housing, age, diet, water intake, type of water source, cohorts, etc
were also studied accordingly and based on their results control measures were devised for
clients (owners of patients). To this end, a predesigned proforma based on the structured
interview of owners was established (Appendix). Moreover, all the above mentioned
determinants were further sub-divided into two categories as:
i. Host determinants – included sex, age, breed of the cats under study.
ii. Environmental/risk factors – involved factors like neuter status, Management
(whether exclusively in-door, exclusively outdoor, or with both the categories), type of diet
fed by the owners (only home cooked, only commercial diet, or combination of both the
83
diet types), cohort (whether single, mates/animals other than cat 'cohort'), vaccination
status of cats till owned by their respective owners (Y/N), historical (past distant history or
present distant history), type of stones (struvite, Ca-oxalate, or mixed type of stones
studied), litter box training (Y/N), litter box type (home-made, commercial), source of water
(fixed, restricted), season-based data (spring, winter, autumn, summer), recurrence (Y/N),
urine color, spayed or neutered.
Diagnosis
Primarily a presumptive diagnosis regarding iFLUTD was based on two approached
under practice, the first one approach was based on the primary diagnostics (involving
complete history, gross clinical signs, complete physical examination and urinalysis profiling)
and the second approach was based on ancillary diagnostics (sero-biochemical profiling,
radiography, hyperkalemia and ultrasonography). Moreover, according to the availability of
electrocardiography was measured in order to check the effect of this disease on cardiac
functioning. To this end, a combination of multiple testing was tried according to the
availability of tests and performed which involved tests like hemato-biochemical evaluation
especially serum cortisol levels (no reference available till yet), urinalysis (Lees, 1996),
radiography (Johnston et al., 1996) and ultrasonography (Voros et. al. 1997) of the patients
that were used for the diagnosis of iFLUTD.
84
I. Primary Diagnostics
a. Medical History
Complete medical history regarding iFLUTD was recorded based on the
structured interview of the owners in the form of questionnaire as mentioned in the
Appendix that involved questions like the present status of animal (whether
intact/castrated males, and intact/hystrectomized females), body weight, vaccination
status, housing type (exclusively indoor, exclusively outdoor, or both of them), age
(at onset of clinical signs), history (of recurrence during past period), type of diet
(exclusively commercial, exclusively home-cooked, or both of the diet type) , any
kind of behavioral alterations noticed (vocalize during taking attempts to urinate; an
indicative of pain), and any kind of other physiological alterations studied (any sign
of hematuria, stranguria, infrequent urination, lack of litter-box training, pollakiuria,
etc).
b. Clinical signs
Complete records of clinical signs related to iFLUTD were recorded
accordingly categorized the disease as obstructive or as non-obstructive. Most
important clinical signs (dysuria, gross hematuria, pollakiuria, vocalization, licking,
and urethral obstruction) indicative of iFLUTD were noted accordingly. Presumptive
diagnosis was made on the basis of complete history (as narrated by owner) and
clinical signs as were on presentation.
c. Physical examination
Thorough physical examination of each of the patient was conducted and
recorded accordingly. The physiological parameters measured in this study were
85
rectal temperature (°F), heart rate (beat per minute), respiratory rate (breath per
minute), and pulse rate (beat per minute). In the present study particular attention was
paid on the appearance (hyperemic/normal) of external urethra.
d. Urinalysis
(i). Collection and Physical examination of urine
In order to collect fresh urine samples feline patient was put in the dorsal
recumbency, ventral abdomen just anterior to the pubis. Then the exposed portion
was clipped using Clipper (Oster # 0). The portion for cystocentesis was sterilized by
the help of spirit (alcoholic swab). The bladder was griped between thumb and
fingers. Then the needle (23 gauge) was attached to 10mL syringe (inserted anterior-
caudally) with an angle of 45° with that of the lower abdomen of the feline. Urine
was then collected in a sterilized container with constant suction as per Crow and
Swlshaw (1987). Again that portion selected was sterilized with the help of spirit
swab. All urine collected was then evaluated for color as well as clarity (turbidity).
Light yellow urine color was taken as normal while a turbid urine sample was taken
to be an indicative of pus, crystals, and less turbid was considered to be normal.
Furthermore, the urine specific gravity was determined by urinometer as per
Benjamin (1985). Moreover, for the evaluation of complete urine status urine test
strips (Medi-Test Combi 10® VET; MACHEREY-NAGEL GmbH & Co. KG
Nuemann-Neander-Str.6-8.52355 Duren, Germany) were used. The test strip showed
semi-quantitative evaluation of the bloodparameters, urobilinogen, bilirubin, protein,
nitrite, ketone, glucose, pH-values, density and leukocytes within urine samples
studied. To this end, urine samples of all the cats under study were collected. All
86
urine samples collected were fresh and not older than 2 hour time period for best
results interpretation Test strip was dipped into the fresh feline urine sample for a
time of approximately 1 second. The excess urine was removed by the help of using
paper towel or the edge of glass. Then the reaction color was compared with that of
the color scale after 30-60 seconds.
(ii). Microscopic Examination of Urine
All the freshly collected samples were plated onto the blood agar as well as
MacConkey’s agar plates for the presence of any bacterial infection (viz., Escherichia
coli). To this end, all samples collected were placed in sterilized glass tube and
centrifuged (3000 rpm; 5 minutes). The supernatant was discarded (by gently tilting)
and the sediment was placed on a clean microscope glass slide (covered with cover
slip), which was then examined under microscope (without using any kind of stain).
For the presence of any kind of infection a single drop of methylene blue was applied
to the edges of cover slip and a Gram stained smear (air-dried, heat-fixed slide)
helped in differentiating the Gram-negative rods (E. coli). The presence of red blood
cells, leukocytes and any kind of crystals within the urine, all samples were examined
under high and lower powers of microscope. The presence of high number of cells
(per high power field; HPF) was mentioned as ‘too numerous to count (TNTC)’.
Other urine parameters like that of pH-value, protein, bilirubin, urobilinogen, and
glucose were determined by using the urine test strips (Medi-Test Combi 10® VET;
MACHEREY-NAGEL GmbH & Co. KG Nuemann-Neander-Str.6-8.52355 Duren,
Germany).
87
(II) Ancillary Diagnostics
The ancillary diagnostics involved sero-biochemical profiling of the cats (n =
502) included in the present study.
(a). Sero-biochemical Profiling
Collection of samples for serum biochemical profiling and analysis
Serum sample from each of the cat under study was collected from blood
samples that were collected from jugular vein in vacutainer (by the help of 3mL
syringe). Then, all the samples were sent to the laboratory for serum concentrations of
creatinine, blood urea nitrogen, and serum electrolytes (bicarbonates, chloride,
potassium, and sodium), etc.
b. Hematology
Collection of blood for hematology
Each blood samples (about 2mL each) was collected jugular vein (by the help
of 3mL syringes), which was then transferred to vacutainer (aseptically). All the
samples collected were labelled with proper date, number allotted by the hospital
authorities to that patient (according to the registration of animal to the hospital) and
name of the owner (where needed). To this end, the hematological parameters
included were total erythrocytic count (millions per micro-litre), total leukocytic
count (thousand per micro-litre), haemoglobin (g/dl), and packed cell volume (in the
form of percentile). The following techniques were applied for haematological
parameter study as:
88
Total Erythrocyte Count
This parameter was performed as per the method described by Benjamin
(1978). The apparatus used for this parameter study comprised of Neubauer counting
chamber, and Thoma erythrocyte diluting pipette, microscope, oil, cover slip, and
Hayem’s diluting fluid as erythrocyte-diluting fluid prepared as mentioned below:
Mercuric chloride 0.5gm
Sodium sulphate 5.0 gm
Sodium chloride 1.0 gm
Distilled water to make 200 ml
The blood sample from each of the cat was drawn into Thoma erythrocyte
diluting pipette till the mark with 0.5. After washing the tip of the pipette the
Hayem’s diluting solution was sucked (into the pipette) upto the mark with 101. Later
on the rubber tubing was eliminated and pipette was held horizontally between thumb
and finger. Whole of the pipette was gently shaken in a circular manner (for at least
3min) with the help of simple wrist movement all the above mentioned activity will
help to enhance lysis of the leukocytes. However, one third of the contents in the
pipette were discarded. Small or a medium sized drop of content collected from the
pipette was poured between the space of counting chamber and cover glass slip that
was placed on the suorting ribs of the counting chamber. That drop (based on content
of pipette) flowed under the cover glass slip (left for 3 min for proper settlement of all
the cells). Then observe the counting chamber under low power of microscope to
examine the nine large squares (basically the central square). Erythrocytes were
counted under high power (X45) found in 5 small squares (80 smallest squares) and
89
average of 3 counting was taken. The above mentioned technique was ended up in the
form of calculations as expressed under (in the form of millions per micro-litre):
Erythrocyte per micro-litre = Cell counted × 10 (0.1mm depth) × 5 (1/5 of Sq. mm) × 200 (1:200 dilutions)
or Total number of erythrocytes per micro-litre = The sum of cell in five small squares × 10,000
Total Leukocyte Count
The total leukocyte count was performed as per described by Benjamin
(1978). Complete apparatus required for that technique comprised of counting
chamber, glass cover slip, Thoma leukocyte diluting pipette, microscope, oil and
leukocytes diluting fluid that was prepared with the help of following material as
follow:
Gentian violet (1% Aquous) 1m
Glacial acetic acid 2ml
Distilled water 100ml
To this end, blood was drawn (up to level of 0.5 as marked on pipette) into the
Thoma leukocyte diluting pipette. Then the diluting fluid was sucked till the marked
point 11. After this the rubber tubing was eliminated while the pipette was held
horizontally between thumb and middle finger of hand. Whole of the pipette was
gently shaken in a circular manner (for at least 3min) with the help of simple wrist
movement all the above mentioned activity will help to enhance lysis of the
leukocytes. However, one third of the contents in the pipette were discarded. Small or
a medium sized drop of content collected from the pipette was poured between the
space of counting chamber and cover glass slip that was placed on the suorting ribs of
the counting chamber. That drop (based on content of pipette) flowed under the cover
90
glass slip (left for 3 min for proper settlement of all the cells). Then observe the
counting chamber under low power of microscope (10 X) to examine the charged
chamber and leukocytes in the four large squares (64 small sq.) that were located on
the corners of the area under study (to be counted). Thus, in the end average of 3
complete and thorough counting was taken as well as calculated as under (expressed
in thousand per micro-litre):
Total Leukocytes per micro-litre = Cell counted × 20 × 10/4 (number of Sq. mm count) or
Total Leukocytes per micro-litre = The sum of cells counted in four corner Sq. × 50
Haemoglobin evaluation
The values of haemoglobin were assessed as per the Sahli’s method also
known for its name as Acid Hematin method according to the method as per
described by Cole (1980). To this end, the material used was diluted (N/10)
hydrochloric acid, pipette, graduated tube, and distilled water. For this technique an
empty graduated tube was taken and a deci-normal (N/10) hydrochloric acid was
poured into the tube up to the level marked as 10. Then, the blood was drawn (into 20
cu mm capacity pipette) up to the level of 20 cu mm marked. After a thorough shake
up the blood was poured into the hydrochloric acid (HCL) solution placed in the tube
and thoroughly mixed with the acid. After a time span of about a minute the fluid was
diluted with the help of distilled water drop wise. The reading collected for
haemoglobin was recorded from the scale by observing and noting the height of
column of the diluted acid hematin, hence the values thus obtained in the end were
expressed in gm/dl.
91
Packed Cell Volume (PCV)
The Packed Cell Volume (PCV) was estimated by using the micro-
haematocrit method as per suggested by Bush (1975). To this end, the material
required and used included capillary tube narrow bore (approx. 1mm diameter and
7mm long), haematocrite machine, wax, and haematocrite tube reader. The
hematocrit tube was completely filled with blood (by capillary action) however the
outer portion was dried with the help of tissue paper while the other end of tube was
sealed with the help of wax to block air entry. Then, the tube was placed in a
centrifugation (high speed; at 10,000 rmp/5 mins) process and centrifuged in a
manner that the sealed end (waxed properly) was placed near the outer rim of
centrifuge machine. Reading of the PCV was recorded based on the special reader (as
the tube has no markings) that was placed (the bottom of the RBC column) exactly
touched the base line of the reader, then moved the tube to right until and unless the
top of plasma layer meet an upper scale as mentioned as mark on the reader. The
PCV values were recorded from the scale at the point where the lines coincided
properly and thus expressed in percentile figures.
c. Diagnostic Imaging
Diagnostic imaging was based on the survey radiograph (as per ) of lateral as well as
ventral abdomen that were taken at low KVp (using 100 MA fixed X-ray unit) in case of
obstructive as well as non obstructive cases of iFLUTD of patients included as part during
this study conducted. Ultrasonography (as per ) of urinary bladder as well as kidneys was also
conducted in all feline patients (using 5MHz sector probe). To this end, the ventral abdominal
portion of each feline patient was properly clipped and swabbed in order to remove dust.
Each of the feline attended was put in the dorsal recumbency in order to visualize kidney and
92
urinary bladder. The thickness of urinary bladder wall and pelvis of kidneys were observed
quite attentively for a proper and accurate diagnosis of idiopathic Feline Lower Urinary Tract
Disease (iFLUTD).
d. Electrocardiography (ECG)
According to the availability of electrocardiography the ECG was performed but not
for all cats being attended. The ECG strips were meant for the proper interpretation for the
presence/absence of hyperkalemia (QRS-interval, widened; shortened in height) that were
observed carefully in patient which had more than long lasting obstruction.
Treatment of Cats (without Urethral Obstruction)
While treating the patients without urethral obstruction primary treatment therapy
involved antispasmodics (those drugs were used for only symptomatic relief) and anti-
inflammatory (those drugs were used for relief of dysuria). The most commonly available
drugs which were used included flavoxate (50mg BID), dantrolene (1mg/kg TID PO) and
Uricon (100mg/cat), and were used according to the availability of drugs at that veterinary
clinic. The anti-inflammatory frequently used in this study were Prednisolone, and Megace
(Tab. 40mg).
The secondary treatment included the DMSO and felines in poor condition sometime
responded well to the intra-vesicular instillation of 10% DMSO (10-20mL). The DMSO
soldrug was left in the bladder for about 10 minutes with the cat under general anesthesia
avoiding stronger solution.
Treatment of Cats (with Urethral Obstruction)
Treatment therapy was conducted accordingly for the felines with urethral
obstruction as per the condition of patient and thus involved different steps like
93
catheterization, bladder irrigation and intravenous fluids. The step that was done immediately
was catheterization while dealing with feline affected with the obstructive form of LUTD. To
this end, sedation with Ketamine (Ketamax, 2mg/kg) was achieved intravenously then the
procedure of catheterization was performed. However, the sedation was not performed in
each and every case. After sedation, the penile area was cleaned properly with warm water,
and a catheter coated with sterilized aqueous lubricant was carefully inserted into the area of
obstruction. After that, a large quantity of Ringer’s Lactated solution was flushed and then
sucked back with the help of syringe as per Osborne et al (1984). The second step involved
bladder irrigation that was performed to remove crystals from the bladder and thus irrigation
of the bladder was performed repeatedly with aliquots of sterile and isotonic solution (20mL).
Then, in the last intravenous fluids (alkalinizing, balanced electrolyte solutions) like Lactated
Ringer’s solution (LRS), were administered accordingly. About third portion of the total
volume of body fluid was administered intravenously according to the condition of patient in
order to overcome dehydration (during first 24 hrs of admission), which was then followed by
maintenance rate administration accordingly. The continuation of fluid depended on the
hydration status of the patient. The fluids also included the potassium that was administered
in the form of dilution with that of a liter of IV fluids (30-40mEq of KCl). The potassium
levels were maintained within the limit range of 0.5mEq/kg/hr.
Measures suggested made to the owners
According to the cases studied two major dietary managements were suggested to the
owners accordingly. The patients mainly affected with the struvite were countered with the
process of crystallization that was directly dealt through diet by using urine acidifiers
(medication with ammonium chloride; 300mg/kg/day, PO or DL-methionine; 500mg/cat BID
PO). On the other hand, the feline patients mainly affected with calcium-oxalate crystals were
suggested with basidifiers either in diet or through medication. As far as the urine volume
94
was concerned, the water intake was also checked accordingly (with respect to the living
condition, climatic condition, age of the patient, the source of water and food contents). In
case of more dried food intake the clients were suggested more moist-food intake instead of
dried food. The clients were suggested to reduce weight of their pets with the complaint of
obstructive LUTD had obesity problem.
PHASE II
The phase II of the present study conducted involved the following.
Experimental observations
All experimental animals (n = 27) were kept in a group of 3 each group having 9
felines (i.e., A, B, and C; Group A was fed with most frequently used commercial diet
available in market, while group B was fed with home cooked food, and the group C was
taken as control). During the therapeutic trial period only those particular feline were
further selected for therapy that got affected with interstitial cystitis.
95
Selection of Animals and setting:
Inclusion criterion of the present study conducted was healthy male cats (n = 27)
due to the fact that higher disease rate was expected among male cats (author’s own
previous experience and data that is unpublished; Moreover the cortisole levels in males is
higher as compared to females as per Lippincot). All feline selected were divided into group
of 3 i.e., A, B, and C, each having 9 cats irrespective of their age or any other selection
criterion. Among 3 groups under study Group A was fed with most frequently used
commercial diet available in market, while Group B was fed with home-cooked food, and
the Group C was taken as control (fed with high moisture diet included commercial as well
as home cooked). Each of the diet defined was given thrice a day with water ad libitum.
Complete experimental study was conducted in the Pet Center, Veterinary Medical Teaching
Hospital (VMTH), University of Veterinary and Animal Sciences (UVAS), Lahore (Pakistan).
Samples collection
The blood samples were collected for hematological parameters from the
cephalic/jugular vein and thus collected in sterilized vacutainers and labeled accordingly for
identification of each of the feline during study. The serum samples were isolated from
about 6mL blood that was drawn into a sterile vacutainer without anticoagulant from each
cat. In order to collect data regarding the whole blood specimen, 2mL blood was collected
into an anticoagulant coated vacutainer from each cat under experimental study. Thin and
thick smears on glass slides were made on-site and labeled accordingly and observed for the
presence of any kind of hemo-parasites. Urine sample was also collected aseptically from
the bladder by the help of the procedure of cystocentesis (Benjamin, 1978).
Samples transportation
96
All samples collected were transported to the laboratory, while observing the critical
requirement of temperature (4°C) during the transportation of the samples collected
accordingly.
Hematological examination
Complete blood count
All blood samples collected were stored in EDTA tubes/vacutainers for data of
complete blood count (CBC) were then transported to the commercial human laboratory, at
Lahore (Pakistan). The critical requirements regarding the temperature (4°C) during the
transportation of the samples collected was taken into account accordingly. The manual
blood counts and evaluation of blood smear preparations were also performed as per
described by Benjamin (1978). The complete blood count results included Packed Cell
Volume (PCV) and White Blood Cell (WBC) count and evaluated as per described by the
Benjamin, (1978).
Sero-biochemical profiles
All serum samples collected were isolated from 6mL blood being drawn into a sterile
vacutainer. The serum samples were collected in EDTA-free tubes/vacutainers. Serum was
collected by following the recommendations described by Benjamin (1978) and stored at -
20°C till further processing. The serum biochemistry were analyzed regarding potassium,
AST, ALT, Bilirubin, BUN, Creatinine, BUN/creatinine ratio, Glucose, albumin, total proteins,
calcium, phosphorus, lactate, sodium, and bicarbonates.
Thin and thick blood smears examination
97
Microscopic examination of GIEMSA (Merk, Germany) stained thin and thick smears
were conducted for any evidence of blood parasites.
Fecal sample examination
Fecal samples were also examined to determine any kind of concurrent intestinal
parasitic infection (Benjamin, 1978).
Monitoring of serum-cortisol levels
Evaluation criterion was dependent upon serum cortisol levels (Pre-, during and
post-treatment observation period; especially after 1 week of onset of feeding and on
appearance of signs / behaviour demonstrating the disease in any of the cat of each group
selected in the present study. During the experiments, cortisol level at 3 different time of
points were juxtaposed with the severity of signs (excessive vocalization, use of litter box,
licking of external genitalia, off feeding, etc). By this way, development of stress (cortisol
levels) was also calculated accordingly in each group.
Therapeutic assessment
After the appearance of either clinical signs or development of interstitial cystitis
(based on ultrasonographic assessment) in each group (A and B; having 9 cats each) in any
of the cat included, 3 cats were treated with Tab Uricon (4mg/kg; Pak Pharma
manufacturers, Pakistan; till yet no work has been done on this drug except annectodectal
reports in the published literature) alone, 3 cats were given Pentosan polysulfate sodium
(PPS) with Vitamin C (@ 2 to 10 mg/kg PO q12 hr; human data available but no study on
feline LUTD), while rest of 3 cats were treated with Pentosan polysulfate sodium (PPS)
alone. Further measures were also adopted accordingly regarding the standard treatment
98
protocols (by massage, followed by fluid therapy, steriod (anti-inflammatory) and antibiotics
against any kind of secondary infection) were used along with above mentioned therapeutic
protocol.
Postmortem:
Postmortem observations were not recorded for dead cats (under study) due to
unavailability of chemicals in laboratory during the therapeutic trial period.
Statistical analysis
All the data was entered and analyzed through SPSS version 16. Quantitative
variables were calculated as mean and standard deviation and qualitative variables were
presented as frequency and percentage. Chi-square test and Fisher Exact test were applied
to see the association in qualitative attribute. ANOVA was also applied to see the average
age in weight in different groups (more than 2 groups, depression, breed and cities). P-value
less than 0.05 were taken as significant. Data regarding hemato-biochemical and urine
profiles were presented as tabulated form. Moreover, the sensitivity, specificity, positive
predictive values, negative predictive values, and kappa (agreement) of different diagnostic
tests performed were also monitored as per described and calculated by Thrusfield (2007)
accordingly. The efficiency of drugs used was also expressed in tabulated form accordingly.
99
CHAPTER 4
RESULTS
According to the main objectives, present study was conducted in client-owned
domesticated felines (n = 502) spontaneously affected with iLUTD belonging to different age
groups as well as gender for a period of two years (2008-2010) in different clinics (VMTH as
well as private clinics) of Lahore, Faisalabad and Islamabad (Pakistan) and the data was
presented in the form of two phases. Phase l included the epidemiological data analysis as
well as efficiency of different diagnostic tools used for the diagnosis of idiopathic Feline
Lower Urinary Tract Disease (iFLUTD), while Phase ll included therapeutic trial only. Detailed
results and proper presentation of data has been shown below.
During the present study many cases presented an excellent picture of
iFLUTD and their images in the form of figures have been shown in this
dissertation as: FIGURE 1 shows hyperemic urethral orifice with urethral plug in a cat
affected with lower urinary tract disease, FIGURE 2 also presents hyperemic urethral orifice
in a cat, FIGURE 3 shows surgical removal of a urolith from urinary bladder of a cat, FIGURE
4 shows wafer like presentation of urolith removed from urinary bladder, FIGURE 5 shows
crystaluria in a urine sample collected through cystocentesis (centrifuged 3500rpm-5 min),
FIGURE 6 shows photomicrograph of sruvite crystals in cat affected with iFLUTD (x 20, and x
40), FIGURE 7 shows right lateral view with fully distended bladder displaced the kidney
anteriodorsally, while FIGURE 8 shows radiograph of a cat with urine filled distended
bladder with renomegaly, FIGURE 9 shows ultrasonogram of a cat with iFLUTD and dilated
pelvis indicative of renomegaly, FIGURE 10 shows ultrasonogram of urinary bladder in a cat
100
with LUTD and multiple bright echoes with acoustic shadowing of urinary bladder indicative
of cystic calculi, FIGURE 11 presents ultrasonographic examination of urinary bladder in a
cat along with the evidence of diffuse thickening of urinary bladder wall and sandy urine
indicative of cystitis, and in the last FIGURE 12 shows the electrocardiogram of cat with
severe hyperkalemia associated with associated with obstructive lower urinary tract disease
and it also presents the increased time interval between QRS complex and severe
bradycardia (<50 bpm).
101
FIGURE 1. Notice angry external urethral orifice with urethral plug in a cat affected with
lower urinary tract disease
FIGURE 2. Notice angry external urethral orifice with urethral plug in a cat affected with
lower urinary tract disease
102
103
FIGURE 3. Surgical removal of a urolith from urinary bladder of a cat
FIGURE 4. Wafer like urolith surgically removed from urinary bladder of a cat
104
FIGURE 5. Notice crystaluria in a urine sample collected through cystocentesis (centrifuged
3500rpm-5 min)
105
FIGURE 6. Photomicrograph of Struvite crystals in cat affected with lower urinary tract
disease (x 20, and x 40)
106
FIGURE 7. Right lateral view of a cat demonstrating fully distended bladder displaced the
kidney anteriodorsally
FIGURE 8. Radiograph of a cat demonstrating urine filled distended bladder with
renomegaly (size of kidney is equal to 3 vertebrae).
107
108
FIGURE 9. Ultrasonogram of a cat with LUTD A dilated pelvis indicative of renomegaly
FIGURE 10. Ultrasonogram of urinary bladder in a cat with LUTD. Multiple bright echoes
with acoustic shadowing of urinary bladder indicative of cystic calculi.
109
110
FIGURE 11. Ultrasonographic examination of urinary bladder in a cat. Evidence of diffuse
thickening of urinary bladder wall and sandy urine indicative of cystitis.
FIGURE 12. Electrocardiogram of cat with severe hyperkalemia associated with associated
with obstructive lower urinary tract disease. Notice increased time interval
between QRS complex and severe bradycardia (<50 bpm).
111
PHASE I
Epidemiological data
Table (1) shows the signalments, body weight and duration of illness of
domesticated cats (n = 502) affected with idiopathic feline lower urinary tract disease
(iFLUTD). To this end, a total of 502 cats were included in the present study. According to
this study conducted, 447 were purebred, while 55 of them were cross bred. Among
purebred felines under study FLUTD was found to be most common among Siamese (300;
59.7%) followed by Non-descript (75; 14.9%) and then Persian 72 (14.3%), respectively
(Table 1). On the other hand, among crossbred felines 43 (8.5%) were long hair domestic,
while rest of the 12 (2.3%) cats were short hair domestic (Table 1). The median age of all
cats (n = 502) under study was 3.64 years. Among these cats 362 were male, while 140 were
female cats. The median weight of all cats was 3.74kg ranging from 2.5 to 5.5kg (Table 1).
112
TABLE 1. Signalments, body weight and duration of illness of domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD)
No. of
Cats
Breed Age (years) Sex Body weight (kg)
502
Purebred Persian = 72
(14.3%)
3 – 5 M/F 4 – 5.5
Non-descript =
75 (14.9%)
3.5 – 4.5 M/F 3 – 4.5
Siamese = 300
(59.7%)
1.5 – 5 M/F 2 – 5
Crossbred SHD* = 12
(2.3%)
2.5 – 6 M 3.5 – 4
LHD** = 43
(8.5%)
2 – 4.5 M/F 2.5 – 3.7
Median = 3.64 M = 362
F = 140
Median = 3.74kg
Range= 2.5-5.5kg
*SHD = Short hair domestic
**LHD = Long hair domestic
113
Table 2 depicts the general medical history of domesticated cats (n = 502) affected
with lower urinary tract disease (LUTD) based on the history as narrated by the owners of
the clients (n = 502) studied. Out of the total number of cats studied 195 (38.8%) had past
distant history while 307 (61.1%) had present distant history. One hundred and thirty three
(133; 26.4%) cats had history of proper vaccination status, while 369 (73.5%) were not
vaccinated ever in past. Out of 502 cats under study, 427 (85.0%) cats were exclusively
indoor, 71 (14.1%) of them were inhabitant of indoor as well as outdoor, while rest of the 4
(7.9%) cats were exclusively outdoor. According to the diet schedule mentioned by the cat
owners 18 (3.5%) were totally on the commercial diet, 87 (17.3%) were fed with both the
commercial as well as home cooked diet, rest of 399 (79.4%) cats were fed exclusively home
cooked diet. The rate of presence of this disease was most common among the intact male
cats (292; 58.1%), then among castrated (167; 33.2%) followed by intact female cats (43;
8.5%).
According to the cardinal parameters studied regarding cats (n = 502) under study,
the median rectal temperature (°F) was found to be 100.2, ranging from below 94 to 102.2,
while median of pulse rate (beat/minute) was 176 ranging from 84 to 200, the
respiration(breaths/minute) ranged from 28 to 80 (median = 32), and the heart rate ranged
from 88 to 231 (median 158) as shown in Table (3).
114
TABLE 2. General medical history of client-owned domesticated felines (n = 502) affected
with idiopathic feline lower urinary tract disease (iFLUTD)
Inclusive criterion of history (as narrated by
the owner)
Absolute No. Frequency (%)
Duration of signs Past distant history 195/502 38.8
Present distant history 307/502 61.1
Median = 5 Range = 2 – 7 days
Vaccination status Vaccinated 133/502 26.4
Non-vaccinated 369/502 73.5
Indoor/outdoor
status
Exclusively indoor 427/502 85.0
Indoor & outdoor 71/502 14.1
Exclusively outdoor 4/502 7.9
Diet Exclusively Commercial 18/502 3.5
Home cooked &
Commercial
87/502 17.3
Exclusively Home
cooked
399/502 79.4
Gender Castrated male 167/502 33.2
Intact male 292/502 58.1
Intact female 43/502 8.5
115
TABLE 3. Cardinal parameters of client-owned domesticated cats (n = 502) affected with
idiopathic feline lower urinary tract disease (iFLUTD)
Parameters Range Median Above
reference
range (%)
Below
reference
range (%)
Rectal
Temperature
(°F)
<94-102.2 100.2 21/502 (4.1) 481/502 (95.8)
Pulse
(beat/minute)
84-200 176 430/502 (85.6) 72/502 (14.3)
Respiration
(breaths/minute)
28-80 32 431/502 (85.8) 71/502 (14.1)
Heart rate
(beats/minute)
88-231 158 421/502 (83.8) 81/502 (16.1)
116
Table (4) shows the absolute numbers as well as the frequency of clinical signs that
were being noted among the observation of domesticated cats (n = 502) during this study.
According to the table (4) the most important sign observed was stranguria (n = 499; 99.4),
then vocalization (n = 423; 84.2%), followed by lethargy (n = 401; 79.8%), anorexia (n = 370;
73.7%), exclusive licking (n = 192; 38.2%), urethral obstruction (n = 98; 19.5%), pollakiuria (n
= 90; 17.9%), dehydration (n = 90; 17.9%), dysuria (n = 55; 10.9%), vomiting (n = 7; 1.3%) and
diarrhea (n = 5; 0.9%).
Table (5) shows urinalysis results of cats affected with LUTD. Median of specific
gravity was found to be 1.052 (ranged from 1.021 to 1.098), while median of pH was 7.37
(ranged from 4.14 to 8.15). Severe (20 + /HPF) crystalluria was observed among 49 (9.7%)
cats out of total of 502 cats under study and moderate (6-8/HPF) crystalluria was found
among 9 (1.17%) of the cats under study. Proteinuria was seen among 51 (3+; 10.1%) and 62
(4+; 12.3%) of the cats. Cystocentesis induced microscopic hematuria (RBCs/HPF) was seen
among 67 (>4; 13.3%) and 380 (TNTC; 75.6%) of the cats under study. On conducting urine
culture, Escherichia coli were exclusively isolated from 7 (1.3%) urine samples.
Data regarding hematobiochemical profiles of cats (n = 502) attended was
presented in tabulated form (Table 6). Blood urea nitrogen (BUN; mg/L) and creatinine
(mg/L) was observed above reference range in 19 (3.7%) and 18 (3.6%) of cats, respectively.
On the other hand, calcium and lactate values were found more than the reference range
available in 7 (20%) and 16 (45%) of cats, respectively (Table 6).
117
TABLE 4. Absolute number and frequencies of important clinical signs (dysuria, pollakiuria,
uretheral obstruction, exclusive licking, vocalization, vomiting, dehydration,
lethargy, anorexia, diarrhea, and stranguria) noted among client-owned
domesticated cats (n = 502) affected with idiopathic feline lower urinary tract
disease (iFLUTD)
Sr. No. Signs Absolute No. Frequency (%)
1 Dysuria 55/502 10.9
2 Pollakiuria 90/502 17.9
3 Urethral obstruction 98/502 19.5
4 Exclusive licking 192/502 38.2
5 Vocalization 423/502 84.2
6 Vomiting 7/502 1.3
7 Dehydration 90/502 17.9
8 Lethargy 401/502 79.8
9 Anorexia 370/502 73.7
10 Diarrhea 5/502 0.9
11 Stranguria 499/502 99.4
118
TABLE 5. Urinalysis results of client-owned domesticated cats (N = 502) affected with
idiopathic feline lower urinary tract disease (iFLUTD)
Parameters Median Range % cats above the
reference range
% cats below the
reference range
Specific gravity 1.052 1.021 – 1.098 499/502 (99.4%) 1/502 (0.1%)
pH 7.37 4.14 – 8.15 480/502 (95.6%) 22/502 (4.3%)
Crystaluria Moderate 6-8/HPF = 09/502 (1.7%)
Severe 20 + /HPF = 49/502 (9.7%)
Proteinuria
+++ (3+)
++++(4+)
51/502 (10.1%)
62/502 (12.3%)
Cystocentesis
induced
microscopic
hematuria
RBCs/HPF:
>4
TNTC
67/502 (13.3%)
380/502 (75.6%)
Urine culture 7/502 (1.3%) (Escherichia coli )
119
TABLE 6. Hemato-biochemical values of client-owned domesticated cats (n = 502) affected
with idiopathic feline lower urinary tract disease (iFLUTD)
Variable Median Range Ref. range % cats
below the
reference
range
% cats
above the
reference
range
BUN (mg/L) 32.7 25 – 35.5 10 - 30 0 19/502
(3.7%)
Creatinine
(mg/L)
1.7 1.2 – 21.9 0.8 - 2 0 18/502
(3.6%)
BUN/Creatinine
(mg/L)
14.8 7.6 – 28.6 7.5 - 32 0 0
Calcium
(mg/dL)
1.10 0.57 – 1.6 1.10 – 1.22 12/502
(34.2%)
42/502
(20%)
Lactate
(mmol/L)
2.2 0.2 – 8.4 1.0 – 2.0 4/502
(11.4%)
92/502
(45%)
Sodium
(mEq/L)
14.3 119 - 142 151 - 165 7/502
(20.0%)
0
Potassium
(mEq/L)
7.8 6.1 – 8.2 3.5 – 5.1 0 367/502
(71%)
Chloride
(mEq/L)
101 89 - 135 96 - 127 2/502
(5.7%)
49/502
(%)
Bicarbonates
(mEq/L)
17 11 - 41 38 - 46 33/502
(94.3%)
0
Glucose (mg/dL) 79 50 - 183 36 - 132 3/502
(8.6%)
20/502 (%)
120
Total protein
(g/dL)
7.9 5.1 – 12.3 6.1 – 8.8 5/502
(14.3%)
280/502
(%)
PCV
(%)
35.5 31 – 55 24 – 45 2/502
(5.7%)
246/502
(%)
RBCs
(106/µL)
7.18 2.83 – 11.3 4.95 – 10.5 2/502
(5.7%)
36/502 (%)
WBCs
(103/µL)
11.3 6.0 – 17.6 3.8 - 19 0 0
Hb
(mg/dL)
11.2 7.9 – 15.5 8.5 – 14.4 0 0
Albumin
(g/dL)
3 1.8 – 4.3 2.4 – 3.8 5/502
(14.2%)
39/502
(8.5%)
Phosphorus
(mg/dL)
5 2.8 - 20 3.0 – 6.6 2/502
5.7%
41/502
(%)
121
Out of total (n = 502) cats 30 cats were diagnosed with mild depression, 357 had
moderate and 97 had severe depression (Table-7). Hyperemic external urethral orifice
without urethral plug was present in 369 (73.5%) and in 133 (26.5%) cats urethral plug was
absent (Table-8). Hyperemic urethral orifice with urethral plug was present in 4.8% of the
cats while absent in 95.2% of the cats (Table-8). The average weight of cats (n = 502) was
found to be 3.74 ±1.21 kg. Among these cats (n = 502), weight of cats with mild depression
was 3.75 ± 1.40 kg, those with moderate depression was 3.72 ± 1.22 kg, and cats with
severe depression was 3.83 ± 1.15 kg. The average weight with depression status was same
(P-value = 0.715) in all cats (Table-7). The average weight of cats with hyperemic external
urethral orifice without urethral plug was 3.72 ± 1.19 kg, and weight of those cats having no
hyperemic external urethral orifice without urethral plug was 3.75 ± 1.22 kg. The average
weight was statistically same (P-value = 0.826) in both groups (Table-8). The average age of
502 cats was 3.64 ± 1.27 years in which the average age of cats having mild depression was
3.26 ± 1.36 years, the age of cats with moderate depression was 3.67 ± 1.25 years, and cats
with severe depression was 3.65 ± 1.31 years. The average age with depression status was
same (P-value = 0.715) in all cats similar to the trend as seen in case of weight among the
502 cats during this study (Table-7). The average age of cats with hyperemic external
urethral orifice with urethral plug was 3.74 ± 1.28 years, and with no hyperemic external
urethral orifice without urethral plug was 3.6 ± 1.27 years. The average age was statistically
same (P-value = 0.297) in both the groups (Table-8).
122
TABLE 7. Descriptive Statistics of Body Weight (kg) and age (years) of domesticated cats (n
= 502) affected with idiopathic feline lower urinary tract disease (iFLUTD) with
respect to depression (viz., mild, moderate or severe)
Depression
Total p-value Mild Moderate Severe
Body
Weight
N 30 375 97 502
0.715
Mean 3.75 3.72 3.83 3.74
Std. Deviation 1.40 1.22 1.15 1.21
Std. Error 0.25 0.06 0.11 0.05
Minimum 1.50 1.50 1.50 1.50
Maximum 5.50 5.50 5.50 5.50
Age
(years)
N 30 375 97 502
0.224
Mean 3.26 3.67 3.65 3.64
Std. Deviation 1.36 1.25 1.31 1.27
Std. Error 0.24 0.06 0.13 0.05
Minimum 0.24 0.06 0.13 0.05
Maximum 1.50 1.50 1.50 1.50
123
TABLE 8. Descriptive statistics of body weight (kg) and age (years) of cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD) with respect to
hyperemic external urethral orifice with (n = 133) and without (n = 369) urethral
plug
Hyperemic external urethral
orifice
Total p-value Without
urethral plug
(n=133)
With
urethral plug
(n=369)
Body
weight
(kg)
Mean 3.72 3.75 3.74
0.826
Std. Deviation 1.19 1.22 1.21
Std. Error 0.10 0.06 0.05
Minimum 1.50 1.50 1.50
Maximum 5.50 5.50 5.50
Age
(years)
Mean 3.74 3.60 3.64
0.297
Std. Deviation 1.28 1.27 1.27
Std. Error 0.11 0.06 .05
Minimum 1.50 1.50 1.50
Maximum 6.00 6.00 6.00
124
In tabulated (Table-9) form the descriptive statistics of body weight (kg) of cats (n =
502) with respect to species (Long Hair Domestic, LHD; Short Hair Domestic, SHD; Non-
Descript, ND; Persian and Siamese) shown that the body weight of Persian breed was
statistically higher (P-value = 0.000) as compared to other species (Table-9).
A total of 207 cats were recorded from the city of Faisalabad (13 had mild
depression, 134 had moderate and 60 had severe depression), while 231 of the cats being
recorded from Islamabad city (11 had mild, 185 had moderate, and 35 had severe
depression), and 64 cats (in which 6 had mild depression, 56 had moderate, while 2 had
severe depression) were attended at the Veterinary Medical Teaching Hospital (VMTH) at
Lahore, Pakistan. The depression was fond to be significantly (P-value = 0.00) different in all
cities of Pakistan included under study (Table-10).
125
TABLE 9. Descriptive statistics of body weight (kg) of domesticated cats (n = 502) affected
with idiopathic feline lower urinary tract disease (iFLUTD) with respect to species
(Long Hair Domestic, LHD; Short Hair Domestic, SHD; Non-Descript, ND; Persian
and Siamese)
Species of cats (n = 502)
LHD* ND** Persian SHD*** Siamese Total p-
value
Body
weight
(kg)
N 43 75 72 12 300 502
0.0000
Mean 3.15 3.36 4.71 3.79 3.69 3.74
Std.
Deviation 0.45 1.20 0.76 0.25 1.28 1.21
Std. Error 0.069 0.13 0.090 0.07 0.07 0.05
Minimum 2.00 1.50 3.00 3.50 1.50 1.50
Maximum 4.00 5.50 5.50 4.00 5.50 5.50
*Long Hair Domestic
**Non-Descript
***Short Hair Domestic
126
TABLE 10. Frequency distribution of depression status among domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD) with respect to
different cities (Faisalabad, Islamabad, and Lahore; Pakistan).
City Total
(n = 502) p-value Faisalabad
(n = 207)
Islamabad
(n = 231)
Lahore
(n = 64)
Depression
in cats (n =
502)
Mild 13 11 6 30
0.000
Moderate 134 185 56 375
Severe 60 35 2 97
Total 207 231 64 502
Total number of feline
cases presented in all
cities
1896 2030 1800 5726
Prevalence 10.9% 11.3% 3.55% 8.7%
127
Frequency distribution of depression among cats (n = 502) with respect to some of
the important factors (viz., Gender, Breed, Season, Housing-type, Recurrence rate, Cohorts,
Litter box usage, Litter box type, Urine color, Type of food, Drinking water, Vaccination
status, Spayed or neutered, Straining to urinate, Presence of stone, Urethral plug, Rate of
survival of death, Diarrhea, Vomiting, Dysuria, Pollakiuria, Vocalization, Dehydration,
Lethargic, Anorexia, Stranguria) being observed according to proforma (Appendix) designed
(Table 11). According to this study, a total of 140 cats were female (8 had mild depression,
111 had moderate depression, and 21 had severe depression). Three hundred and sixty two
(362) were male cats (22 had mild depression, 264 had moderate, while 76 had severe
depression). Statistically depression status was insignificant in both genders and the
depression status was also statistically same in all breeds (P-value = 0.469). The depression
was highly significant (P-value = 0.00) in winter season followed by summer, autumn and
spring. There were 427 cats whose residence was exclusively in-door, 4 were from outdoor
housing and 71 were from the mixed housing status. The depression status insignificant (P-
value = 0.760) within all housing status (Table 11). There were 187 cats that had the
recurrence rate in which 12 had mild depression, 137 had moderate depression, and 38 had
severe depression. There were 315 cats which showed the recurrence rate among which 18
had mild depression, 238 had moderate depression, and 59 had severe depression. The
depression status was not associated (P-value = 0.847) with recurrence rate. There were
total of 356 cats which were not cohorts and among these cats 11 had mild depression
status, 273 had moderate depression status, and rest of the 64 had severe depression
status. The depression status was however strongly associated (P-value = 0.269) with the
cohorts. There were 236 cats which were used to litter box. Among those cats, 13 had mild
depression, 203 had moderate, while 50 had severe depression. There were 236 cats which
128
were not used to litter box and among theses cats 17 had mild depression, 172 had
moderate, while 47 had severe depression status. The depression status was highly related
(P-value = 0.00) to the litter box usage as well as associated (P-value = 0.246) with the type
of litter box used. There were 362 cats with blood tinged urine among which 6 had mild
depression, 262 had moderate depression, and 94 had severe depression. There were a
total of 140 cats with normal urine color and in this group of cats 24 had mild depression
113 had moderate and 3 had severe depression. Statistically the depression status was
statistically higher (P-value = 0.00) in cats with abnormal urine color (Table 11). According to
the data analyzed (Table 11), depression status was not associated (P-value = 0.623) with
the types of food (viz., commercial diet, home cooked food, and third diet plan based on
both of the commercial as well as home cooked diet) then the similar trend of insignificance
was followed by the drinking water (Fixed and Restricted; P-value = 0.574), vaccination
status (Yes and No; P-value = 0.921), and the status of being spayed or neutered (P-value =
0.450). There were 140 cats with no straining to urine but had mild (n = 16), moderate (n =
113), and severe (n = 11) depression. There were 362 cats which showed straining to urine
in which 14 had mild, 262 had moderate and 86 had severe depression. The depression
status was strongly and significantly (P-value = 0.00) associated with the stone in bladder.
Similarly, the depression status was also associated (P-value = 0.00) with the urethral plug.
Types of stones and their presence was also associated (P-value = 0.00) with the depression
status of cats. The rate of survival or death was also associated (P-value = 0.00) with
depression. There were 5 cats which had diarrhea and all showed severe depression, and
both were significantly associated (P-value = 0.003) with each other. However, there was no
relationship (P-value = 0.444) between duration of illness and depression. Dysuria and
depression status among cats was strongly associated (P-value = 0.000) with each other, and
129
similar trend was seen regarding strong association between dehydration (P-value = 0.000),
lethargy (P-value = 0.000), anorexia (P-value = 0.002) and depression status of cats during
this study, while statistically insignificant (P-value = 0.774) relationship was found between
stranguria and depression (Table 11).
130
TABLE 11. Frequency distribution of depression among domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD) with
respect to some of the important factors being observed according to
proforma designed (Appendix)
Important factors studied
Depression (n = 502)
Total
(n = 502) p-value Mild
(n=30)
Moderat
e
(n=375)
Severe
(n=97)
Gender-
based
Male 22 272 76 370 0.294
Female 28 111 20 132
Breed-based
Long hair
domestic 3 35 5 43
0.496
Non-
Descript 6 55 14 75
Persian 6 48 18 72
Small hair
domestic 0 8 4 12
Siamese 15 229 56 300
Season-based
distribution
Autumn 0 39 11 50
0.000 Spring 1 37 6 44
Summer 9 90 45 144
Winter 20 209 35 264
Housing type-
based
distribution
Exclusively
Indoor 26 320 81 427
0.760 Exclusively
Outdoor 0 4 0 4
In-door + 4 51 16 471
131
Out-door
Recurrence
rate
No 18 238 59 315 0.847
Yes 12 137 38 187
Cohort No 19 273 64 356
0.269 Yes 11 102 33 146
Litter box
usage
No 17 172 47 236 0.496
Yes 13 203 50 266
Litter box
type
Commercia
l 5 60 16 30
0.447 Home
made 9 145 170 375
No 16 30 46 97
Urine color
Blood
tinged 6 262 94 362
0.000
Normal 24 113 3 140
Type of food
Commercia
l diet 2 11 5 18
0.623
Extensively
Home
cooked
22 299 78 399
Home
cooked +
Commercia
l diet
6 65 14 85
Drinking
water
Fixed 8 71 20 99 0.574
Restricted 22 304 77 403
Vaccination No 23 275 71 369 0.921
132
status Yes 7 100 26 133
Spayed or
neutered
Castrated 7 128 32 167
0.450 Nil 19 213 60 292
Spayed 4 34 5 43
Straining to
urinate
No 16 113 11 140 0.000
Yes 14 262 86 362
Presence of
stone
No 27 363 60 450 0.000
Yes 3 12 37 52
Urethral plug No 30 365 63 458
0.000 Yes 0 10 34 44
Stone if any
Ca- oxalate 0 3 3 6
0.000 Mixed 2 2 3 7
None 27 363 60 450
Struvite 1 7 31 39
Rate of
survival of
death
Died 0 11 26 27
0.000 Survive 30 364 71 475
Diarrhea No 30 374 93 497
0.003 Yes 0 1 4 5
Vomiting No 29 374 92 495
0.001 Yes 1 1 5 7
Dysuria No 29 365 53 447
0.000 Yes 1 10 44 55
Pollakiuria No 27 357 28 412
0.000 Yes 3 18 69 90
133
Vocalization No 4 74 1 79
0.000 Yes 26 301 96 423
Dehydration No 27 357 28 412
0.000 Yes 3 18 69 90
Lethargy No 6 92 3 101
0.000 Yes 24 283 94 401
Anorexia No 7 113 12 132
0.002 Yes 23 262 85 370
Stranguria No 0 2 1 3
0.774 Yes 30 373 96 499
134
Frequency distribution of depression among cats (n = 502) with respect to
HEUOWUP (Hyperemic external urethral orifice without urethral plug) with respect to some
of the important factors (viz., Gender, Breed, Season, Housing-type, Recurrence rate,
Cohorts, Litter box usage, Litter box type, Urine color, Type of food, Drinking water,
Vaccination status, Spayed or neutered, Straining to urinate, Presence of stone, Urethral
plug, Rate of survival of death, Diarrhea, Vomiting, Dysuria, Pollakiuria, Vocalization,
Dehydration, Lethargic, Anorexia, Stranguria) being observed according to proforma
(Appendix) designed as shown in Table (12). According to this study, a total of 140 cats were
female (107 of the female cats had hyperemic urethral rim), while out of 362, 262 of the
male cats had hyperemic urethral orifice without urethral plug. Gender-based distribution
record showed that the male gender was mainly affected (P-value = 0.356) without urethral
plug problem. Moreover, the depression status (mild, moderate and severe), season
(winter, autumn, summer and spring) and presence of urethral plug was directly associated
(0.000) with HEUOWUP. The breed-based distribution was not statistically significant (P-
value = 0.649) with the HEUOWUP. The presence of hyperemic urethral orifice without
urethral plug presence (HEUOWUP) was also found in relation with that of hoursing type
(exclusively in-door, outdoor and the mixed housing status), cohorts, recurrence rate, litter
box training, usage of litter box type (commercial and home-made), urine color, drinking
water serving type (Fixed and restricted), straining, presence of stone and stone type (Ca-
oxalate, struvite or mixed type of stones), rate of survival or death, vomiting, duration of
illness, dysuria, pollakiruia, exclusive licking, dehydration, and anorexia. No significant
relationship was found between HEUOWUP and breeds (Long hair domestic, Short hair
domestic, Non-descript, Siameses and Persian), types of food (Commercial, home cooked or
both of the home cooked as well as commercial diet), vaccination status, being spayed or
135
neutered, diagnosis (Ultrasonography, radiography or urinalysis), diarrhea, cities (Lahore,
Islamabad, or Faisalabad), and vocalization status of the cats included under this portion of
study conducted (Table 12).
Frequency distribution of depression among cats (n = 502) with respect to HEUO-UP
(Hyperemic external urethral orifice with urethral plug) with some of the important factors
(viz., Gender, Breed, Season, Housing-type, Recurrence rate, Cohorts, Litter box usage, Litter
box type, Urine color, Type of food, Drinking water, Vaccination status, Spayed or neutered,
Straining to urinate, Presence of stone, Urethral plug, Rate of survival of death, Diarrhea,
Vomiting, Dysuria, Pollakiuria, Vocalization, Dehydration, Lethargic, Anorexia, Stranguria)
being observed according to proforma (Appendix) designed as shown in Table (13). The
depression status (mild, moderate and severe) and diagnosis (Urinalysis, Ultrasonography,
or Radiography) were directly associated (0.000) with HEUOWUP. According to this study, a
total of 140 cats were female (only 4 of the female cats had hyperemic urethral rim), while
out of 362, 20 of the male cats had hyperemic urethral orifice with urethral plug. Gender-
based distribution record showed that the male gender was mainly affected (P-value =
0.209) with urethral plug problem. Moreover, the breed-based distribution was also
statistically significant (P-value = 0.140) with the presence of plug formation in all breeds
(Siamese = 10, Non-descript = 6, Persian = 4, Small hair domestic = 2, Long hair domestic =
2). The presence of hyperemic urethral orifice with urethral plug formation was highly
significant (P-value = 0.042) in summer season followed by winter, autumn and spring. No
significant relationship (P-value = 0.875) between type of housing viz., exclusively in-door,
outdoor and the mixed housing status and HEUO-UP (Table 13). There were cats that had
the recurrence rate and cohorts were associated (P-value = 0.186 and 0.012, respectively)
with HEUO-UP. The HEUO-UP status was however not associated (P-value = 0.764 and
136
0.924, respectively) with the litter box training as well as litter box type. The HEUO-UP
status was highly related with urine color, type of food (viz., commercial diet, home cooked
food, and third diet plan based on both of the commercial as well as home cooked diet), and
the types of stones involved (Table 13). The presence of Hyperemia was highly associated
with that of diarrhea, dysuria, type of food (Table 13), while this type of condition is not so
much associated or statistically insignificant relationship with the vaccination of the cats
attended along with the status of being spayed or neutered, rate of survival or death,
vomiting, duration of illness, cities affected and even drinking water serving type whether it
is fixed or restricted (Table 13). Graphical presentation of tables (TABLE-12 and TABLE-13)
have also been presented after the tabulated form of data.
137
TABLE 12. Frequency distribution of depression among domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD) and Hyperemic
external urethral orifice without urethral plug (HEUOWUP) with respect to some
of the important factors being observed according to proforma designed
(Appendix)
Important factors studied
Hyperemic external urethral
orifice without urethral plug
(HEUOWUP) Total p-value
No (n = 133) Yes (n=369)
Depression
Mild 24 6 30
0.000 Moderate 85 290 375
Severe 24 73 97
Gender-based Female 33 107 140
0.356 Male 100 262 362
Breed-based
LHD 13 30 43
0.649
ND 22 53 75
Persian 22 50 72
SHD 4 8 12
Siamese 72 228 300
Season-based
Autumn 22 28 50
0.000 Spring 10 34 44
Summer 52 92 144
Winter 49 215 264
Housing type
Exclusively Indoor 109 318 427
0.166 Exclusively Outdoor 0 4 4
Indoor + Outdoor 24 47 71
Recurrence rate No 79 236 315 0.351
138
Yes 54 133 187
Cohorts No 86 270 356
0.064 Yes 47 99 146
Litter box usage No 70 166 236
0.130 Yes 63 203 266
Litter box type
Commercial 23 63 86
0.231 Home made 41 143 184
No 69 163 232
Urine color Blood tinged 90 272 362
0.183 Normal 43 97 140
Type of food
Commercial diet 5 13 18
0.792
Extensively home
cooked 108 291 399
Home cooked +
Commercial diet 20 65 85
Drinking water
serving type
Fixed 22 77 99 0.282
Restricted 111 292 403
Vaccination
status
No 98 271 369 0.957
Yes 35 98 133
Spayed or
neutered
Castrated 45 122 167
0.880 Nil 78 214 292
Spayed 10 33 43
Straining to
urinate
No 42 98 140 0.268
Yes 91 271 362
Diagnosis Urinalysis 36 96 132
0.972
Urinalysis + 44 124 168
139
Ultrasonography
Urinalysis +
Ultrasonography +
Radiography
53 149 202
Presence of
stones in
bladder
No 123 332 455
0.395 Yes 10 37 47
Presence of
urethral plug
No 107 351 458 0.000
Yes 26 18 44
Types of stones
(if any)
Ca-oxalate 1 5 6
0.295 Mixed 4 3 7
None 118 332 450
Struvite 10 29 39
Rate of survival
or death
Died 11 16 27 0.085
Survived 122 353 475
Diarrhea No 132 365 497
0.741 Yes 1 4 5
Vomiting No 129 366 495
0.064 Yes 4 3 7
Duration of
illness
Present distant
history 75 232 307
0.189
Past distant Hx 58 137 195
City
Faisalabad 51 156 207
0.432 Islamabad 61 170 231
Lahore 21 43 64
Dysuria No 108 339 447
0.001 Yes 25 30 55
140
Pollakiuria No 105 307 412
0.273 Yes 28 62 90
exclusive licking No 74 236 310
0.091 Yes 59 133 192
Vocalization No 21 58 79
0.985 Yes 112 311 423
Dehydration No 105 307 412
0.273 Yes 28 62 90
Lethargic No 25 76 101
0.657 Yes 108 293 401
Anorexia No 30 102 132
0.253 Yes 103 267 370
Stranguria No 1 2 3
0.788 Yes 132 367 499
141
TABLE 13. Frequency distribution of depression among domesticated cats (n = 502)
affected with idiopathic feline lower urinary tract disease (iFLUTD) and Hyperemic
external urethral orifice with urethral plug (HEUO-UP) with respect to some of the
important factors being observed according to proforma designed (Appendix)
Hyperemic external
urethral orifice with
urethral plug (HEUO-UP)
Total
(n =
502)
p-value
No (n = 478) Yes (n = 24)
Depression
Mild 30 0 30
0.000 Moderate 368 7 375
Severe 80 17 97
Gender-
based
Female 136 4 140 0.209
Male 342 20 362
Breed-based
LHD 41 2 43
0.14
ND 69 6 75
Persian 68 4 72
SHD 10 2 12
Siamese 290 10 300
Season-
based
Autumn 47 3 50
0.042 Spring 41 3 44
Summer 132 12 144
Winter 258 6 264
Housing type
Exclusively Indoor 406 21 427
0.875 Exclusively Outdoor 4 0 4
Indoor + Outdoor 68 3 71
Recurrence No 303 12 315 0.186
142
rate Yes 175 12 187
Cohorts No 344 12 356
0.021 Yes 134 12 146
Litter box
usage
No 224 12 236 0.764
Yes 254 12 266
Litter box
type
Commercial 82 4 86
0.924 Home made 176 8 184
No 220 12 232
Urine color Blood tinged 338 24 362
0.002 Normal 140 0 140
Type of food
Commercial diet 16 2 18
0.391
Extensively home
cooked 380 19 399
Home cooked +
Commercial diet 82 3 85
Drinking
water
serving type
Fixed 93 6 99
0.505 Restricted 385 18 403
Vaccination
status
No 350 19 369 0.520
Yes 128 5 133
Spayed or
neutered
Castrated 157 10 167
0.556 Nil 279 13 292
Spayed 42 1 43
Straining to
urinate
No 140 0 140
0.002 Yes 338 24 362
Diagnosis Urinalysis 131 1 132
143
Urinalysis +
Ultrasonography 157 11 168
Urinalysis +
Ultrasonography +
Radiography
190 12 202
Presence of
stones in
bladder
No 6 0 6
0.040 Yes 7 0 7
Presence of
urethral plug
No 429 21 450 0.859
Yes 36 3 39
Types of
stones (if
any)
Ca-Oxalate 22 5 27
0.000 Mixed 456 19 475
None 474 23 497
Struvite 4 1 5
Rate of
survival or
death
Died 22 5 27
0.707 Survived 456 19 475
Diarrhea No 474 23 497
0.001 Yes 4 1 5
Vomiting No 471 24 495
0.550 Yes 7 0 7
Duration of
illness
Present distant history 295 12 307 0.251
Past distant History 183 12 195
City
Faisalabad 197 10 207
0.789 Islamabad 219 12 231
Lahore 62 2 64
Dysuria No 445 2 447 0.000
144
Yes 33 22 55
Pollakiuria No 410 2 412
0.000 Yes 68 22 90
Exclusive
licking
No 308 2 310 0.000
Yes 170 22 192
Vocalization No 79 0 79
0.030 Yes 399 24 423
Dehydration No 410 2 412
0.000 Yes 68 22 90
Lethargic No 100 1 101
0.046 Yes 378 23 401
Anorexia No 130 2 132
0.041 Yes 348 22 370
Stranguria No 3 0 3
0.697 Yes 475 24 499
FIGURE FIGURE
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
Diagnostic efficiency of different diagnostic tests
In next portion of study (Table 14), a total of 306 cats were selected for comparative
evaluation and assessment of different diagnostic tests used for the diagnosis of Feline
Urologic Syndrome (FUS). The selection criterion was based on the complete data regarding
each of all the 6 diagnostic tests (viz., Urinalysis, Hyperkalemia, Clinical signs, Radiography,
Serum crortisol levels and Ultrasonography) being performed on each cat with complete
back history (viz., present and past-distant history) of each case attended at VMTH, Lahore,
Islamabad, and Faisalabad, Pakistan during the year 2008 to 2010. Out of 306 cats under
study, 208 (76 with present history only and 132 with both present as well as past distant
history) had history of FUS, while 98 were selected as healthy cats based on the previous
history record of FUS. Among 132 of the diseased patients selected, 52 had stones (6
suffering with Ca-Oxalate crystals, 39 suffering with struvite and rest of the 7 with mixed
crystalline matrix) as shown in Table (14). Agreement between all the 6 diagnostic tests (viz.,
Urinalysis, Hyperkalemia, Clinical signs, Radiography, Serum crortisol levels and
Ultrasonography) was shown in Table (15). On comparing diseased (n = 208) and healthy (n
= 98) cats, the highest agreement 0.812 (0.70-0.92%) was found between Clinical signs and
Ultrasonography followed by 0.734 (0.62-0.84) between Radiography and Hyperkalemia,
followed by 0.729 (0.62-0.83; between serum cortisol level and ultrasonography), then
0.622(0.51-0.72; between radiograph and ultrasound), 0.617 (0.51-0.72; between serum
cortisol level and hyperkalemia), 0.613 (0.50-0.72; between clinical signs and serum cortisol
level), 0.586 (0.47-0.69; between clinical signs and hyperkalemia), 0.567 (0.45-0.67;
between urinalysis and serum cortisol level), 0.567 (0.46-0.66; between urinalysis and
clinical signs), 0.543 (0.44-0.64; between urinalysis and ultrasound), 0.524 (0.42-0.62;
between clinical signs and radiography), while lowest agreement was seen between
164
ultrasonography and hyperkalemia (0.449; 0.35-0.54%). In order to evaluate sensitivity and
specificity of diagnostic tests (viz., Hyperkalemia, Clinical signs, Radiography, Serum crortisol
levels and Ultrasonography) all the above mentioned tests were compared with that of the
standard (Gold standard; Urinalysis was taken as the gold standard in this study) as shown in
Table (16). All tests but serum cortisol level (80.303; 70.70-89.89%) showed 100 percent
specificity. The calculated sensitivities of serum cortisol, ultrasonography, clinical signs,
hyperkalemia, and radiography against iLUTD were 84.167 (79.54-88.78), 75.000 (69.52-
80.47), 73.333 (67.73-78.92), 65.417 (59.39-71.43), 48.333 (42.01-54.65), respectively.
Serum cortisol was found to be significantly more sensitive (P<0.05) than ultrasonography,
clinical signs, hyperkalemia, and radiography. The negative predictive value of each test
(serum cortisol, ultrasonography, clinical signs, hyperkalemia, and radiography) was as
follows: 58.2, 52.3, 50.7, 44.2, and 34.7, respectively (Table 16).
165
TABLE 14. Different diagnostic tests (viz., Urinalysis, Hyperkalemia, Clinical Signs,
Radiography, Serum cortisol levels, and Ultrasonography) performed against the
diagnosis of idiopathic feline lower urinary tract disease (iFLUTD)
Groups of
cats under
study (I and
II)
Different tests performed for the diagnosis of iFLUTD***
Total
cats
under
study
(n =
306)
Urinalysis Hk*** Clinical
Signs
Radiography Serum
cortisol
levels
Ultrasonography
Diseased
cats with
history
(present +
past
distant) of
iFLUTD*
I (n =
208)
208 137 180 110 170 164
Apparently
healthy**
cats
II (n =
98)
32 20 0 6 45 12
*iFLUTD – idiopathic Feline Lower Urinary Tract Disease
**without any clear clinical signs of idiopathic Feline Lower Urinary Tract Disease
***Hyperkalemia
Important note – Out of total of 208 cats, 76 had present history also having stones, while
rest of 132 had present as well as past distant history. Healthy cats (n = 98) had no history of
idiopathic feline lower urinary tract disease.
95
TABLE 15. Performance and Kappa (agreement) statistics for different diagnostic tests (viz. Urinalysis, Hyperkalemia, Clinical Signs,
Radiography, Serum cortisol levels, and Ultrasonography) performed for the diagnosis of idiopathic feline lower urinary tract disease
(iFLUTD)
Hyperkalemia Kappa
values
Ultrasonography Kappa
values
Serum
cortisol
levels
Kappa
values
Radiography Kappa
values
Clinical
Signs
Kappa
values
+ - + - + - + - + -
Urinalysis + 157 83 0.449
(0.35-0.54)
176 64 0.543
(0.44-0.64)
202 38 0.567
(0.45-0.67)
116 124 0.288
(0.20-
0.36)
180 60 0.567
(0.46-
0.66) - 0 66 0 66 13 53 0 66 0 66
Clinical Signs + 137 43 0.586
(0.47-0.69)
164 16 0.812
(0.70-0.92)
170 10 0.613
(0.50-0.72)
110 70 0.524
(0.42-
0.62)
- 20 106 12 114 45 81 6 120
Radiography + 116 0 0.734(0.62-
0.84)
116 0 0.622(0.51-
0.72)
116 0 0.411(0.32-
0.50)
- 41 149 60 130 99 91
Serum
cortisol
levels
+ 157 58 0.617
(0.51-0.72)
176 39 0.729
(0.62-0.83)
- 0 91 0 91
96
TABLE 16 – Evaluation of sensitivity and specificity of diagnostic tests (viz., Hyperkalemia,
Clinical signs, Radiography, Serum crortisol levels and Ultrasonography) with that
of the standard (Gold standard; Urinalysis was taken as the gold standard) against
idiopathic feline lower urinary tract disease (iFLUTD)
Diagnostic tests
for equine
glanders
Sensitivity (95%CI) Specificity (95%CI) Positive Predictive
Value (95%CI)
Negative Predictive
Value
(95%CI)
Serum cortisol
levels
84.167 (79.54-
88.78)
80.303 (70.70-
89.89)
93.953 (90.76-
97.13)
58.242 (48.10-
68.37)
Ultrasonography 73.333 (67.73-
78.92)
100 100 50.769 (42.17-
59.36)
Radiography 48.333 (42.01-
54.65)
100 100 34.737 (27.96-
41.50)
Clinical Signs
100 100 52.381 (43.66-
61.10)
Hyperkalemia 65.417 (59.39-
71.43)
100 100 44.295(36.31-52.27)
97
PHASE – II
In the present study, phase II involved 27 cats that were kept in group of 3 i.e., A, B,
and C, each having 9 cats irrespective of their age or any other selection criterion. Among 3
groups under study Group A was fed with most frequently used commercial diet available in
market, while Group B was fed with home-cooked food, and the Group C was taken as
control (fed with high moisture diet included commercial as well as home cooked). Each of
the diet defined was given thrice a day with water ad libitum. Complete experimental study
was conducted in the Pet Center, Veterinary Medical Teaching Hospital (VMTH), University
of Veterinary and Animal Sciences (UVAS), Lahore (Pakistan). For therapeutic assessment
each main group (A, B and C; having 9 cats each) was further sub-divided into group of three
as AI, AII, AIII, BI, BII, BIII, CI, CII, and CIII (3 cats in each sub-group). Felines in the sub-group I
were treated with Tab Uricon (4mg/kg; Pak Pharma manufacturers, Pakistan; till yet no work
has been done on this drug except annectodectal reports in the published literature) alone,
II were given Pentosan polysulfate sodium (PPS) with Vitamin C (@ 2 to 10 mg/kg PO q12 hr;
human data available but no study on feline LUTD), while III were treated with Pentosan
polysulfate sodium (PPS) alone. Further measures were also adopted accordingly regarding
the standard treatment protocols (by massage, followed by fluid therapy, steriod (anti-
inflammatory) and antibiotics against any kind of secondary infection) were used along with
above mentioned therapeutic protocol (Table 17 and Table 21). Furthermore, the clinical
picture, hemato-biochemical, and serum-biochemical profiles of male cats (n = 27) during (3
months of diet experimental trial) and post-therapy observation period were tabulated in
Table 18, Table 19 and Table 20. Therapeutic assessment of Pentosan polysulfate sodium
(PPS) during and after completion of therapy was compared with that of diet viz-a-viz
development of interstitial cystitis (IC) and cortisol level (CL) viz-a-viz clinical severity scores
98
(CSS) during and after therapy completion in cats (n = 27) affected with idiopathic Feline
Lower Urinary Tract Disease (Table 21). The severity scores were developed according to the
clinical signs by the author herself for ease which included the following (Table 21):
1. Anorexia, lethargy, and frequent urination
2. + vocalization during urination
3. + no urination and excessive licking of penile region
4. + urethral obstruction, diarrhea and vomiting
99
TABLE 17. Summary of pharmaceutical preparations administered to cats (n = 27)
experimentally affected with idiopathic feline lower urinary tract disease (iFLUTD)
Pharmaceutical preparation Protocol
Number of animals 27 male cats
Therapy:
Detressor muscle relaxant (Oral uricone; s.i.d., 44mg/kg)
Glucosamine Glycan (Oral Pentosan polysulfate sodium, GSK; s.i.d., 2-10mg/kg)
Vitamin C (Sandoz CAC; b.i.d., 0.3mg/kg)
Duration of experimental protocol (days): About a year
Dosing Total number of doses Oral: 180 × respective dose
Daily doses/kg body weight:
Detressor muscle relaxant (mg) @44 mg
Glucosamine Glycan (mg) @2-10 mg
Vitamin C (mg) @0.3 mg
100
TABLE 18. The frequencies of different clinical signs appeared during study period and
post-treatment observation period among 27 male cats
Sr. # Clinical signs appeared Clinical signs appeared
during study period
Clinical signs recovered post-
treatment observation period
1 Dysuria 21/27 21/27
2 Pollakiuria 21/27 17/27
3 Urethral obstruction 1/27 1/27
4 Exclusive licking 22/27 21/27
5 Vocalization 23/27 23/27
6 Vomiting 2/27 1/27
7 Dehydration 17/27 14/27
8 Lethargy 15/27 13/27
9 Anorexia 25/27 25/27
10 Diarrhea 9/27 7/27
11 Stranguria 20/27 20/27
101
TABLE 19. Range of hemato-biochemical profiles of male cats (n = 27) before (day - 0),
during (3 months of diet experimental trial) and post-therapy observation period
Parameters Day 0
(before)
Three Month (during
diet experimental
trial)
Six Month After
Therapy
(post)
Total RBCs
(106/µL)
1.92 – 7.3 (Reference
range - 4.95-10.5)
3.23 – 8.9 (Reference
range - 4.95-10.5)
4.49 – 9.8 (Reference
range - 4.95-10.5)
Total WBCs
(103/µL)
7.0 – 16.9 (Reference
range – 3.8 - 19)
6.2 – 14.7 (Reference
range – 3.8 - 19)
7.1 – 15.3 (Reference
range – 3.8 - 19)
Hb (mg/dL) 6.5 – 13.1 (Reference
range - 8.5 – 14.4)
7.9 – 14.1 (Reference
range - 8.5 – 14.4)
7.2 – 13.8 (Reference
range - 8.5 – 14.4)
PCV (%) 34 – 44 (Reference
range – 24 - 45)
22 – 40 (Reference
range – 24 - 45)
26 – 34 (Reference
range – 24 - 45)
102
TABLE 20. Serum-biochemical values of cats (n = 27) affected with lower urinary tract
disease
Variable Median Range DAY-0 Before
treatment
After
treatment
BUN (mg/L) 30.7 25 – 35.5 (Reference
range – 10-30)
6/27 21/27 3/27
Creatinine
(mg/L)
2.7 1.2 – 21.9 (Ref. range –
0.8-2)
7/27 22/27 4/27
BUN/
Creatinine
(mg/L)
13.8 7.6 – 28.6 (Ref. range –
7.5-32)
6/27 23/27 4/27
Calcium
(mg/dL)
1.0 0.57 – 1.6 (Ref. range –
1.10-1.22)
9/27 15/27 1/27
Lactate
(mmol/L)
4.4 0.2 – 8.4 (Ref. range –
1.0-2.0)
8/27 16/27 9/27
Sodium
(mEq/L)
16.5 119 – 142 (Ref. range –
151-165)
6/27 15/27 5/27
Potassium
(mEq/L)
7.8 6.1 – 8.2 (Ref. range –
3.5-5.1)
3/27 19/27 5/27
Chloride
(mEq/L)
104 89 – 135 (Ref. range –
96-127)
3/27 18/27 1/27
Bicarbonates
(mEq/L)
21 11 – 41 (Ref. range – 38-
46)
2/27 21/27 3/27
Glucose
(mg/dL)
79 50 – 183 (36-132) 2/27 20/27 0/27
Total protein 8.9 5.1 – 12.3 (6.1-8.8) 2/27 22/27 3/27
103
(g/dL)
Albumin
(g/dL)
2 1.8 – 4.3 (2.4-3.8) 3/27 14/27 1/27
Phosphorus
(mg/dL)
7 2.8 – 20 (3.0-6.6) 3/27 20/27 4/27
104
TABLE 21. Therapeutic assessment of Pentosan polysulfate sodium (PPS) during and after
completion of therapy along with comparison of effect of food viz-a-viz
development of interstitial cystitis (IC) and cortisol level (CL) viz-a-viz clinical
severity scores (CSS) during and after therapy completion in cats (n = 27) affected
with idiopathic Feline Lower Urinary Tract Disease (iFLUTD)
Groups
(n = 27)
Sub-
groups
(n = 27)
BEFORE DURING AFTER COMPLETION OF
THERAPY
Cortisol
level
(nmol/l
)
Cortisol
level
(nmol/l
)
Severit
y
scores
*
Interstitia
l cystitis
(Yes/No)
Cortisol
level
(nmol/l
)
Severit
y
scores*
Interstitia
l cystitis
(Yes/No)
A
(on
commercia
l diet; n =
9)
AI**
(n = 3)
200,
187,
153
320,
289,
315
3, 0, 1 Y, N, N 119,
149,
219
1, 0, 0 N, N, N
AII***
(n = 3)
153,
295,
300
129,
195,
451
2, 1, 2 Y, Y, Y 222,
298,
336
1, 0, 3 N, N, Y
AIII***
* (n =
3)
415,
128,
139
390,
228,
339
1, 0, 2 N, N, Y 256,
139,
398
0, 0, 0 N, N, N
B
(on home
cooked
food; n =
9)
BI**
(n = 3)
125,
356,
129
225,
516,
218
1, 3, 1 Y, Y, N 320,
312,
167
0, 0, 0 N, N, N
BII***
(n = 3)
319,
327,
229
227,
129,
146
1, 1, 1 N, N, Y 118,
198,
219
2, 1, 1 Y, N, N
BIII***
* (n =
3)
213,
312,
219
416,
422,
349
1, 2, 2 N, N, Y 322,
315,
221
1, 0, 3 N, N, Y
C
(on home
cooked
and
commercia
l with
CI**
(n = 3)
498,
359,
312
339,
448,
213
1, 2, 1 N, N, N 178,
412,
128
0, 1, 0 N, N, N
CII***
(n = 3)
212,
179,
245
334,
270,
348
2, 3, 3 N, Y, N 124,
227,
412
3, 3, 3 Y, Y, Y
105
balanced
water; n =
9)
CIII***
* (n =
3)
323,
195,
178
418,
129,
222
2, 0, 1 N, N, Y 419,
124,
332
2, 2, 3 Y, Y, Y
* Severity scores:
1. Anorexia, lethargy, and frequent urination
2. + vocalization during urination
3. + no urination and excessive licking of penile region
4. + urethral obstruction, diarrhea and vomiting
** - Treated with detressor muscle relaxant (Tablet uricon)
*** - Treated with pentosan polysulfate sodium (PPS) with vitamin C
**** - Treated with pentosan polysulfate sodium (PPS) without vitamin C
106
CHAPTER 5
DISCUSSION
According to the main objectives, present study was conducted in client-owned
domesticated felines (n = 502) spontaneously affected with idiopathic (no defined etiology)
Feline Lower Urinary Tract Disease (iFLUTD) belonging to different age groups as well as
gender for a period of two years (2008-2010) in different clinics including Veterinary
Medical Teaching Hospitals (VMTH) as well as private clinics from the city of Lahore,
Faisalabad and Islamabad, Pakistan. The present study involved two phases. Phase l
included the epidemiological analysis as well as efficiency of different diagnostic tools used
for the diagnosis of idiopathic Feline Lower Urinary Tract Disease (iFLUTD), while Phase ll
included therapeutic trial only.
The results obtained from data collected have been discussed accordingly as shown
below.
PHASE I
Epidemiological data
According to the present study undertaken (Table - 1), out of 502 cats were
presented with the complaint of iFLUTD, 447 were purebred, and 55 were cross bred.
However, there is no particular breed predilection (Elcock, 1981; Greene and Scott, 1983)
according to some of the workers studied iFLUTD previously. In the present study, the most
common breed observed was Siamese (300; 59.7%) followed by Non-descript and then
Persian, respectively. Contrarily, Persian breed were reported to be at high risk as compared
to that of Siamese according to literature (Lewkowicz 1979, Willeberg 1975, Willeberge and
107
Priester 1976, Walker 2007). The present study showed that the mean age of cats was 3.64
years which is inline with that described by Willeberg (1984). The present study showed that
according to gender-wise distribution of cats there were 362 cats belonging to male gender
much more than female (n = 140). Likewise, higher risks of iFLUTD have been reported in
male gender than in female both in the past as well as recent studies (Willeberg 1984,
Defauw et al. 2011). In the present study, median weight of all cats was 3.74kg ranging from
2.5 to 5.5kg. In one of the studies conducted in the past it was observed that 34 % of the
cases were due to obesity issue (Walker, 1977), weight proved to be the major issue in
those cases. Moreover, the results of present study showed that majority of the cases were
intact male and females as compared to neutered or spayed one which is contrary to the
statement mentioned in the past by Foster (1967) and Dorn (1973). According to present
study stress is the main factor involved in causing iFLUTD similar to the study conducted by
Walker (2007).
With respect to the data observed in the present study more cats (n = 369) had no
history of proper vaccination than those vaccinated in the past. Majority of cats (n = 427)
were exclusively indoor as per Fennell (1974) and Willeberg (1975). According to the diet
schedule, this disease was found more frequent in those cats that were fed exclusively with
home cooked diet as compared to the canned/commercial food. Contrarily, literature cited
(Fennell 1974, Willeberg 1975, Walker et al. 1977) showed that iFLUTD was basically
associated with the commercial diets mainly along with the outdoor trend among cats. The
present study conducted negates the previous trend seen in this disease and mainly those
cats were found affected with the disease normally fed with the home-cooked diet as well
as their strong association with indoor housing system. The rate of presence of this disease
was found to be most common among the intact male cats than other groups (castrated
108
male or female gender) the reason for this may be the pakistani owners prefer to have male
cats as their pets than females in order to avoid litter problem. No significant results were
recorded regarding the cardinal parameters of the cats and varied a lot from case to case.
According to the present study the most important clinical signs observed included
stranguria, vocalization, lethargy, anorexia, exclusive licking, urethral obstruction,
pollakiuria, dehydration, dysuria, vomiting and diarrhea. All clinical features as mentioned
and observed in the present study were inline with those discussed in the past literature
(Walker 2007, Markwell et al. 1998, Defauw et al. 2011). The term ‘Retention of urine’ has
been presented as a common condition usually in cats as per Kirk (1925), who discussed that
the major cause leading to this problem was urethral obstruction by a material (sabulous)
and other causes may include cystitis and calculi. Another term ‘Feline Urologic Syndrome
(FUS)’ was invented in 1970, according to that invention FUS was meant by dyuria,
urolithiasis, urethral obstruction, and hematuria. Previously conducted studies (Markwell
and Buffington, 1994) have shown that FUS is not the term based on the concept of being a
single disease entity, however it is includes a set of unique urologic problem with a set of
signs viz., depression, anorexia, weakness, hypothermia, vomiting, and dehydration and
hyperkalemia are also found to be the additional signs of LUTD (Buffington et al. 1997).
Latter form (non-obstructive) includes the voiding of bloody urine (small amount) usually
seen outside the litter box (if in use), while licking of penis is frequently observed among the
tom cats (this sign resembles with constipation). Majority of times crystaluria seen is
composed of struvite as per Norsworthy (1998). All type of clinical signs and causes were
recorded in the present study were inline with that of Gerber et al. (2005) and Defauw et al.
(2011).
109
In the present study urinalysis results of cats under study showed that median specific
gravity was 1.052, while pH was 7.37 that slightly basic in nature. Moreover, severe (20 +
/HPF) crystalluria and proteinuria was observed among majority of cats under study which
are inline with the observations of Markwell et al. (1998) and Bailiff et al. (2008). On
conducting urine culture, Escherichia coli were exclusively isolated from urine samples. In
spontaneous cases of urethral obstruction the urine pH is usually acidic (Osbaldiston and
Taussing 1970, Markwell et al. 1998, Lee and Brobatz 2003). Moreover, the evidence of
bacterial cultures are not always proven to be negative (Schecter, 1970), proper bacterial
infection related to this condition has been documented previously among 2% of young cats
affected with LUTD.
Data regarding hematobiochemical profiles of cats (n = 502) under study blood urea
nitrogen (BUN; mg/L) and creatinine (mg/L) was observed above reference range in majority
of cats, respectively. On the other hand, calcium and lactate values were found more than
the reference range available in similar trends, respectively (Table 6). All hemato-
biochemical profiling was inline with the previous trends observed in different studies
(Walker, 2006). Likewise in the present study conducted PCV was found to be much higher
which is indicative of dehydration and low water intake (Walker 2006, Defauw et al. 2011)
All cats presented in the present study showed signs of depression and 30 of the
cats were diagnosed with mild depression, 357 had moderate and 97 had severe depression
(Table-7). Hyperemic external urethral orifice without urethral plug was present in 369
(73.5%) and hyperemic external urethral orifice with urethral plug was present in 4.8% of
the cats. Obesity was found to be one of the major factors as the average weight of cats (n =
502) was found to be 3.74 ±1.21 kg. As the cats with severe depression weight was 3.83 ±
110
1.15 kg much higher than that of mild and moderate depression form of the disease. The
average weight of cats was found to be near to obesity and included adult cats more than
the young cats as studied previously (Walker 1977, Walker, 2007).
In tabulated (Table-9) form the descriptive statistics of body weight (kg) of cats (n =
502) with respect to species (Long Hair Domestic, LHD; Short Hair Domestic, SHD; Non-
Descript, ND; Persian and Siamese) shown that the body weight of Persian breed was
statistically higher (P-value = 0.000) as compared to other species under study (Defauw et al.
2011). Contrarily previous work done showed different trend of breed predilection
(Lewkowicz 1979, Willeberg 1975, Willeberge and Priester 1976, Walker 2007).
According to this study the depression was found to be significantly (P-value = 0.00)
different in all cities of Pakistan included under study (Table-10). The present study showed
that this disease is prevalent in Pakistan, the prevalence rate found was about 8.7% in three
cities (10.9% in Faisalabad, 11.3% in Islamabad, and 3.55% in Lahore) but still no report
found because of cognizance of Pakistan veterinarians, misdiagnosed as constipation or
colic, present study attempted to bring iFLUTD into the reportive of small animal
practitioners, the present study debunked the popular notion iFLUTD related to commercial
cat foods only as suggested in many recent reports (Defauw et al. 2011).
Idiopathic form of feline lower urinary tract disease (iFLUTD) till yet exists in two
major forms as obstructive and non-obstructive. The former form (obstructive) includes
uroliths (matrix-crystalline plugs) lodged in tapering end of the urethra. These uroliths are
actually part of the messed up precipitates made up of matrix and extra mineral contents.
Many different studies conducted in the past (Stone and Barsanti, 1992) have shown that
more than about 90 percent felines had struvite crystal compared to any other mineral that
111
were found predominantly in few cases. According to this study, majority of the cats
belonging to both the genders had moderate form of depression. Statistically depression
status was insignificant in both genders and the depression status was also statistically same
in all breeds (P-value = 0.469). Season-based distribution showed that the depression was
highly significant (P-value = 0.00) in winter season followed by summer, autumn and spring.
The depression status proved to be insignificant (P-value = 0.760) within all housing status.
However, according to previous studies indoor housing management increases stress level
leading to iFLUTD and to counter this we need to enrich the inner housing environment (Van
Roojen 1991, Koolhaas et al. 1999, Buffington 2002, Van De Weerd et al. 2003). To this end,
hiding places should be made within homes so that cats might feel home as a secured place
(Kry and Cassey, 2007). The depression status was not associated (P-value = 0.847) with
recurrence rate. Contrarily, the recurrence and stress levels are related to each other
according to Buffington et al. (2006). The depression status was however strongly associated
(P-value = 0.269) with the cohorts which is not inline with the previous studies conducted
(Fennell, 1973). The depression status was highly related (P-value = 0.00) to the litter box
usage as well as associated (P-value = 0.246) with the type of litter box used which is similar
to the previous studies conducted (Walker et al. 1977, Fennell 1975, Defauw et al. 2011).
Statistically the depression status was statistically higher (P-value = 0.00) in cats with
abnormal urine color. Depression status was not associated (P-value = 0.623) with the types
of food (viz., commercial diet, home cooked food, and third diet plan based on both of the
commercial as well as home cooked diet) then the similar trend of insignificance was
followed by the drinking water (Fixed and Restricted; P-value = 0.574), vaccination status
(Yes and No; P-value = 0.921), and the status of being spayed or neutered (P-value = 0.450).
However, previous records show that diet and drinking water are main factors affecting
112
iFLUTD (Fennell 1974, Jackson and Tovey 1977, Willeberg 1981, Markwell et al. 1998,
Robertson 1999, Defauw et al. 2011). Furthermore, in the present study it was observed
that most of the cats were on the home cooked diet and not on canned or commercial food
products which is contrary to the statement given in the literature (Walker et al. 1977,
Willeberg 1975). The depression status was strongly and significantly (P-value = 0.00)
associated with the stone in bladder which is similar to the study conducted by Osbrone et
al. (1984). Similarly, in the same pattern the depression status was also associated (P-value =
0.00) with the urethral plug in the present study. The type of stone most frequently
observed in the present study was struvite as indicated by Osborne et al. (1984) and Kirk et
al. (1995) and it was found to be associated (P-value = 0.00) with the depression status of
the cats. The rate of survival or death was also associated (P-value = 0.00) with depression.
There were 5 cats which had diarrhea and all showed severe depression, and both were
significantly associated (P-value = 0.003) with each other. However, there was no
relationship (P-value = 0.444) between duration of illness and depression. Dysuria and
depression status among cats was strongly associated (P-value = 0.000) with each other, and
similar trend was seen regarding strong association between dehydration (P-value = 0.000),
lethargy (P-value = 0.000), anorexia (P-value = 0.002) and depression status of cats during
this study, while statistically insignificant (P-value = 0.774) relationship was found between
stranguria and depression (Table 11). The present study showed that majority of urinary
precipitates was struvite as compared to Ca-Oxalate and mixed type (non-specific). It was
observed that by the change in urine pH the struvite activity product also changed as
compared to the change in concentration of any of the crystalloid components of struvite. In
the present study it was observed that by reducing pH (urine) with the help of dietary
management/manipulation the feline urine becomes quite under-saturated for struvite
113
leading to the dissolution of the executed material along with the ceased crystallization and
ceased crystal growth within that vicinity (Markwell and Buffington, 1994). The present
study showed a significant difference (P<0.05) in water intake, urine volume and its specific
gravity varying a lot with the amount of water contents present in food which is similar to
the study conducted by Gaskell (1985) who indicated significant difference (P<0.05) in above
mentioned factors when the water content of food were 45% and 70%, respectively, which
shows that diet change (from dry to wet form) is a part of disease prevention along with
other managemental practices done in case of this condition. In male cats – mostly found –
mostly owners prefer to have male cats as their pets than females in order to avoid litter
problem. This study conducted also compared the Hyperemic external urethral orifice with
and without urethral plug with that of other factors while in data previously studied no such
study was found.
Diagnostic efficiency of different diagnostic tests
In end of Phase I, a total of 306 cats were selected for comparative evaluation and
assessment of different diagnostic tests used for the diagnosis of Feline Urologic Syndrome
(FUS). To this end, total of 6 diagnostic tests (viz., Urinalysis, Hyperkalemia, Clinical signs,
Radiography, Serum crortisol levels and Ultrasonography) being performed on the cats with
complete back history (viz., present and past-distant history) among those cases attended at
VMTH, Lahore, Islamabad, and Faisalabad, Pakistan during the year 2008 to 2010. According
to literature (Roger and Chew 2005) no clinical signs or their combination are supposed to
be the exact diagnosis however, it is made up of signalement, history, physical examination,
time course of disease, urinalysis and urinary tract imaging. Keeping in view the above
mentioned criteria the diagnostic tests viz., Urinalysis, Hyperkalemia, Clinical signs,
114
Radiography, Serum crortisol levels and Ultrasonography for comparison were included in
the present study. On comparing diseased (n = 208) and healthy (n = 98) group of cats, the
highest agreement 0.812 (0.70-0.92%) was found between Clinical signs and
Ultrasonography followed by 0.734 between Radiography and Hyperkalemia, followed by
0.729 (between serum cortisol level and ultrasonography), then 0.622 (between radiograph
and ultrasound), 0.617 (between serum cortisol level and hyperkalemia), 0.613 (between
clinical signs and serum cortisol level), 0.586 (between clinical signs and hyperkalemia),
0.567 (between urinalysis and serum cortisol level), 0.567 (between urinalysis and clinical
signs), 0.543 (between urinalysis and ultrasound), 0.524 (between clinical signs and
radiography), while lowest agreement was seen between ultrasonography and
hyperkalemia (0.449; 0.35-0.54%). In case of sensitivity and specificity of diagnostic tests
(viz., Hyperkalemia, Clinical signs, Radiography, Serum crortisol levels and Ultrasonography)
performed all tests except serum cortisol level (80.303) showed 100 percent specificity. The
calculated sensitivities of serum cortisol, ultrasonography, clinical signs, hyperkalemia, and
radiography against iLUTD were in descending dorder, respectively. Serum cortisol was
found to be significantly more sensitive (P<0.05) than ultrasonography, clinical signs,
hyperkalemia, and radiography. The negative predictive values of serum cortisol,
ultrasonography, clinical signs, hyperkalemia, and radiography) were found in the similar
trend as that of sensitivities. Radiography is the most cost effective and to be used only
when needed as per Jhonston et al. (1996). According to Roger and Chew (2005)
ultrasonography is less sensitive and urinalysis identifies hematuria and proteinuria both
quite accurately.
115
PHASE II
Experimental trial
According to the Phase II of study, the iFLUTD involves many complex interactions
both between the central nervous and endocrine system. The main sympathetic nervous
system plays a pivotal role (in the form of release of catecholamines viz., norepinephrine
(NE) and epinephrine) in his regard. The two factors stress and pain enhance the
sympathetic nervous system outflow which leads to accelerated NE and other
catecholamine under some stress condition compared to normal felines (Westropp, Kass et
al. 2006). Directly or indirectly the phenomenons up regulate the inflammatory response.
The felines affected with iFLUTD have significantly decreased serum cortisol responses
compared to normal cats and have smaller adrenal glands (Westropp, Welk et al. 2003). The
reason to select the felines was that they got much more similarities between regarding
interstitial cystitis in humans (Buffington, Chew et al. 1994; Buffington, Blaisdell et al. 1996;
Pereira, Aguiar et al. 2004). According to literature, Glycosaminoglycan (GAG) therapy
proved to be successful in about 10-20% of human cases of interstitial cystitis. Its main
mechanism involved bladder mucosa, as well as provide analgesic and anti-inflammatory
effects. In one study undertaken it was concluded that decreased urinary concentrations of
GAG in felines affected with interstitial cystitis compared to normal cats (Buffington,
Blaisdell et al. 1996). Its significance is still unknown, but the decreased in GAG excretion
could be due to alterations in synthesis, metabolism or bladder permeability. However,
another case report on the use of sodium pentosan polysulfate in a cat with biopsy-
diagnosed interstitial cystitis (Clasper 1990). There are many GAG formulations available in
humans as well as veterinary use (viz., human product of pentosan polysulfate is Elmiron®,
116
Baker Norton; 50 mg/cat, PO, BID and veterinary polysulfated GAGs like Adequan®, Luitpold;
5 mg/kg, IM, twice weekly x 4-6 weeks, then weekly or less). It is a natural substrate for the
biosynthesis of GAGs and is available combined with the GAG chondroitin sulfate as
Cosequin® (Nutramax). In another study by Gunn-Moore and Shenoy (2004), oral
glucosamine was compared to placebo in a randomized, double-blind, placebo-controlled
trial. There was no significant difference between the two groups based on the owners’
assessment (of mean health score), average monthly clinical score, and average number of
days with clinical signs. So, its quite hard to recommend GAG therapy and need of hour is to
conduct more veterinary studies to get information and authenticity for its use against
iFLUTD.
UPSHOT:
1. Idiopathic Feline Lower Urinary Tract Disease (iFLUTD) is present among cats in
Pakistan.
2. Poor cognizance of Pakistani veterinarians to this disease and is misdiagnosed as
Constipation/Colic.
3. Owners should be made aware of the risk factors leading to this disease.
4. Present study attempted to bring FUS into the reportire of Small Animal
Practitioners in Pakistan
5. The present study debunked the popular notion ‘iFLUTD related to commercial cat
foods only, contrarily it does occur in cats on home cooked foods and strong
association - - indoor housing
6. Additional work is still needed in the area of its epidemiology as well as treatment
protocols defined.
117
7. Academicians in Veterinary Pathology, Veterinary Medicine should embrace this
malady in D.V.M. Curricula in Pakistani Universities.
CHAPTER 6
SUMMARY
Idiopathic Feline Lower Urinary Tract Disease (iFLUTD) has been known as a major
as well as important problem throughout the world especially the veterinary profession.
Nicks of this problem also found in Pakistan, however the veterinarians are usually unable to
properly diagnose this disease due to lack of knowledge as well as the ancillary diagnostic
equipment availability for this disease. Present study was divided into two phases. Phase – 1
included clinico-epidemiological data. To this end, target of more than 502 domesticated
client-owned cats of either sex, age, breed, etc showing signs of feline lower urinary tract
disease (FLUTD) as per Buffington (1994) were examined accordingly from 3 different cities
(Lahore, Faisalabad, and Islamabad) of Pakistan). All data collected was based on a
predesigned proforma by using structured interview of the owners. Diagnosis was solely
based on serum-cortisol levels, urinalysis, radiography and ultrasonography. Phase II
involved experimental trial. The data obtained from whole of the study was then presented
in tabulated form as frequencies and percentages. Treatment and outcome of the disease
were also analyzed accordingly.
118
According to the present study conducted it is proved that iFLUTD is present among
the cats in Pakistan. Its proper cognizance among the Pakistani veterinarians is still non-
existent and is misdiagnosed as colic or constipation issues in cats. The present study was
undertaken to bring iFLUTD into the reportive of small animal practitioners working in
Pakistan. The present study debunked various previous notions like iFLUTD is associated
with commercial diets and canned foods only if we talk about this region majority of cases
were noticed that had home-cooked food given by the owner. Moreover, cases in Siamese
breed are larger than Persian breed. It has been strongly associated with Indoor housing
management. Additional work is still needed to explore untouched areas of epidemiology
including factors other than those being studied in the previous literature. Academicians in
veterinary pathology and veterinary medicine of Pakistani universities should embrace this
malady in the Doctor of Veterinary Medicine (DVM) curricula.
According to the present study results it is concluded that two factors like stress and
pain accelerate the sympathetic nervous system outflow compared to normal felines leading
to the inflammatory response. Thus the stress factor must be reduced in the form of making
hiding places for cats at home to reduced down the fear factor along with enhancing the
feeling of owes for that particular place. Moreover, some more practices should be
performed by the owner to reduce down the stress factor like playing with the pet, giving
full attention, placing toys and other attractive things like yarn balls at the feline places
(where they live/placed). There was no significant difference found between the groups
based on the food with health score along with the therapeutic judgment. Hence, it is
recommended that more experiments should be performed on larger scale to assess GAG
therapy on increased number of felines and need of hour is to conduct more veterinary
studies to get information and authenticity for its use against iFLUTD.
119
From this study conducted, I recommend to the owners that the cats must be
provided with the indoor hiding places and play with their pets in order to reduce the stress
factor that increases the risk of idiopathic lower urinary tract disease. Moreover, the trend
of home-cooked diet should be reduced along with increase in water intake by the cat.
120
CHAPTER 7
LITERATURE CITED
Bailiff NL, Westropp JL, Nelson RW, Sykes JE, Owens SD, Kass PH. 2008. Evaluation of urine
specific gravity and urine sediment as risk factors for urinary tract infections
in cats. Vet Clin Pathol. 37(3):317-22.
Barker J, Povey RC. 1973. The feline urolithiasis syndrome: a review and an inquiry into the
alleged role of dry cat food in its aetiology. J Small Anim Pract 14:445–57.
Blaivas JG, Labib KB, Michalik SJ. 1980. Cystometric response to propantheline in detrusor
hyperreflexia: therapeutic implications. J Urol. 124:259-262.
Blount WP. 1931. Urinary calculi. Vet J 87:561–576.
Bovee KC, Reif JS, Maguire TG. 1979. Recurrence of feline urethral obstruction. J Am Vet
Med Assoc 174:93–6.
Buffington CA, Blaisdell JL, Michalik SJ. 1996. Decreased urine glycosaminoglycan excretion
in cats with interstitial cystitis. J Urol. 155(5): 1801-4.
Buffington CA, Chew DJ, Kendall MS. 1997. Clinical evaluation of cats with nonobstructive
lower urinary tract diseases. J Am Vet Med Assoc. 210:46–50.
Buffington CAT, Chew DJ, DiBartola SP. 1996. Interstitial cystitis in cats. Vet Clin North Am
Small Anim Pract. 26:317-326.
121
Buffington CAT, Chew DJ, Kendall MS, Scrivani PV, Thompson SB, Blaisdell JL, Woodworth
BE. 1997. Clinical evaluation of cats with nonobstructive urinary tract
diseases. J Am Vet Med Assoc. 210:46-50.
Buffington CAT, Chew DJ. 1993. Presence of mast cells in submucosa and detrusor of cats
with idiopathic lower urinary tract disease. J Vet Intern Med. 7:126.
Buffington CAT, Chew DJ. 1995a. Does interstitial cystitis occur in cats? In: Current
Veterinray Therapy XII. Kirk RW, Bonagura JD, editors. WB Saunders Co.
Philadelphia USA. p. 1009-1011.
Buffington CAT, Chew DJ. 1995b. Idiopathic lower urinary tract disease in cats- Is it
interstitial cystitis? In: Proceeding 13th Am College Vet Intern Med Forum.
Ohio. p. 517.
Buffington CAT, Chew DJ. 1997. Feline lower urinary tract disease in cats. The Ohio State
experience. In: Proceeding 15th Am College Vet Intern Med Forum. Ohio. p.
343-346.
Buffington CAT, Westropp JL, Chew DJ, Bolus RR. 2006. Clinical evaluation of multimodal
environmental modification (MEMO) in the management of cats with
idiopathic cystitis. J Feline Med Surg. 8:261-268.
Buffington CAT. 1994. Lower urinary tract disease in cat: New problems, new paradigms. J
Nutr. 124:2634S-2651S.
Buffington CAT. 2002. External and internal influences on disease risk in cats. J Am Vet Med
Assoc. 220:994-1002.
122
Chew DJ, DiBartola SP, Fenner WR. 1986. Pharmacologic management of urination. In:
Kirk’s Current Veterinary Therapy IX. Small Animal Practice. Kirk RW, editor.
9th ed. WB Saunders Co. Philadelphia USA. p. 1207.
Ching SV, Fettman MJ, Hamar DW. 1989. The effects of chronic dietary acidification using
ammonium chloride on acid-base and mineral metabolism in adult cats. J
Nutr. 119:902-915.
Clasper M. 1990. A case of interstitial cystitis and Hunner's ulcer in a domestic shorthaired
cat. N Z Vet J 38(4): 158-60.
Defauw PA, Van de Maele I, Duchateau L, Polis IE, Saunders JH, Daminet S. 2011. Risk factors
and clinical presentation of cats with feline idiopathic cystitis. J Feline Med
Surg. 13(12):967-975.
Dorn CR, Saueressig S, Schmidt DA. 1973. Factors affecting risks of urolithiasis-cystitis-
uretheritis in cats. Am J Vet Res. 35:433-436.
Dow SW, Fettman MJ, Smith KR. 1990. Effects of dietary acidification and potassium
depletion on acid-base balance, mineral metabolism and renal function in
adult cats. J Nutr. 120:569-578.
Elbadawi A. 1997. Interstitial cystitis: A critique of current concepts with new proposal for
pathologic diagnosis and pathogenesis. Urol. 49:14-40.
Elcock L. 1981. Feline urologic syndrome – a review. Feline Pract. 11:6-11.
El-Mansoury M, Boucher W, Sant GR, Theoharides TC. 1994. Increased urine histamine and
methylhistamine in interstitial cystitis. J Urol. 152:350-353.
123
Engle GC. 1977. A clinical report of 250 cases of feline urological syndrome. Feline Pract.
7:24.
Fabricant CG, Gillespie JH, Krook L. 1971. Intracellular and extracellular mineral crystal
formation induced by viral infection of cell cultures. Infect Immunol. 3:416-
419.
Fabricant CG. 1984. The feline urological syndrome induced by infection with a cell-
associated herpesvirus. Vet Clin North Am Small Anim Pract. 14:493-502.
Fennell C. 1974. Some demographic characteristics of the domestic cat population in Great
Britain with particular reference to feeding habits and the incidence of the
feline urologic syndrome. J Small Anm Pract. 16:775-783.
Fennell C. 1975. Unpublished summary report on the ‘RBL’- study.
Fettman MJ, Coble JM, Harnar DW. 1992. Effect of dietary phosphoric acid supplementation
on acid-base balance and mineral and bone metabolism in adult cats. Am J
Vet Res. 53: 2125-2135.
Fischer MJE, Paulussen JJC, Horbach DA. 1995. Inhibition of mediator release in RBL-2H3
cells by some H1antagonists derived antiallergic drugs: Relation to
lipophilicity and membrane effects. Inflamm Res. 44:92-97.
Fisher J. 1955. Urolithiasis or urethral impaction in the cat. J Am Vet Med Assoc. 127:21–
123.
Foster SJ. 1967. The ‘urolithiasis’ syndrome in male cats. J Small Anm Pract. 8:207-214.
124
Frenier SL, Knowlen GG, Speth RC. 1992. Urethral pressure response to alpha-adrenergic
agonist and antagonist drugs in anesthetized healthy male cats. Am J Vet
Res. 53:1161-1165.
Gaskell CJ, Denny HR, Jackson OF. 1978. Clinical management of the feline urological
syndrome. J Small Anim Pract. 19:301-314.
Gerber B, Boretti FS, Kley S, Laluha P, Müller C, Sieber N, Unterer S, Wenger M, Flückiger
M, Glaus T, Reusch CE. 2005. Evaluation of clinical signs and causes of lower
urinary tract disease in European cats. J Small Anim Pract. 46(12):571-7.
Golub RE. 1997. Forum letters. Vet Forum. 14:36.
Greene RW and Scott RC. 1983. Diseases of the bladder and urethera. In: Textbook of
Veterinary Internal Medicine, Saunders WB.
Gunn-Moore D and Shenoy C. 2004. Oral glucosamine and the management of feline
idiopathic cystitis. J Fel Med Surg. 6(4): 219-226.
Holm-Bentzen M, Sondergaard I, Haid T. 1987. Urinary excretion of a metabolite of
histamine (1,4-methyl-imidazole-acetic acid) in painful bladder disease. Br J
Urol. 59:230-233.
Holzworth J. 1965. Urolithiasis in cats. In: Kirk’s Current Veterinary Therapy. Small Animal
Practice. Kirk RW, editors. WB Saunders Co Philadelphia USA. p. 410.
Jackson OF and Tovey JD. 1977. Water balance studies in domestic cats. Feline Pract. 7:30-
33.
125
Jackson OF. 1972. The dry cat food controversy. Urolithiasis in laboratory and domestic cat.
Vet Rec. 91:292-293.
Johnston GR, Feeney DA, Rivers WJ, Weichselbaum R. 1996. Diagnostic imaging of the felinw
lower urinary tract. Vet Clin North Am Small Anim Pract. 26(2):401-15.
Johnston GR, Feeney DA, Rivers WJ. 1996. Diagnostic imaging of the feline lower urinary
tract. Vet Clin North Am Small Anim Pract. 26:401-415.
Jones B, Sanson RL, Morris RS. 1997. Elucidating the risk factors of feline urologic syndrome.
NZ Vet J. 45:100–8.
Jones BR, Sanson RL, Morris RS. 1994. Elucidating the risk factors of feline urologic
syndrome. Presented at World Small Animal Veterinary Association. Durban.
South Africa. 1994. (Unpublished data).
Kalkstein TS, Osborne CA, Kruger JM. 1999. Feline idiopathic lower urinary tract disease -
Part II. Comp Continue Edu Pract Vet. 21:148-154.
Kirk H. 1925. Urinary deposits and retention. In: The diseases of the cat and it general
management. London: Bailliere, Tindall and Cox. p. 261–7.
Kirk H. 1925.The diseases of Cat. Balliere. Tindall and Cox. London UK. p. 261.
Kirk, C. A., Ling, G. V., Franti, C. E. & Scarlett, J. M. (1995) Evaluation of factors associated
with development of calcium oxalate urolithiasis in cats. J. Am.
Koolhaas JM, Korte SM, De Boer SF, Van Der Vegt BJ, Van Reenen CG, Hopster H. 1999.
Coping styles in animals: current status in behavior and stress-physiology.
Neuroscience and Biobehavioral Reviews. 23:925-935.
126
Kruger JM, Fitzgerald S. 1996. Light microscopic evaluation of urinary bladder biopsy
specimens from 70 cats with chronic idiopathic lower urinary tract disease.
Michigan State University. (Unpublished data).
Kruger JM, Osborne CA, Goyal SM, Wickstrom SL, Johnston GR, Fletcher TF, Brown PA. 1991.
Clinical evaluation of cats with lower urinary tract disease. J Am Vet Med
Assoc. 199:211-216.
Kruger JM, Osborne CA, Goyal SM. 1991. Clinical evaluation of cats with lower urinary tract
disease. J Am Vet Med Assoc. 199:211–6.
Kruger JM, Osborne CA. 1990. The role of viruses in feline lower urinary tract disease. J Vet
Intern Med. 4:71-78.
Kry K, Casey R. 2007. The effect of hiding enrichment on stress levels and behavior of
domestic cats in a shelter setting and the implications for adoption
potential. Anim. Welf. 16: 375-384.
Lawler DF, Sjolin DW, Collins JE. 1985. Incidence rates of feline lower urinary tract disease in
the United States. Feline Pract. 15:13-16.
Lees GE, Osborne CA. 1983. Feline urinary tract infections. In: Current Veterinary Therapy
VIII: Small Animal Practice. Kirk RW, editor. WB Saunders Co Philadelphia.
USA. p. 1058-1061.
Lees GE. 1996. Bacterial urinary tract infections. Vet Clin North Amer Small Anim Pract.
26:297–304.
127
Lewis LD, Morris ML. 1984. Feline Urological syndrome: Causes and clinical management.
Vet Med. 79:323.
Lewkoweiz J. 1979. Baseline search package. Unpublished users’ guide, with an example of
epidemiologic analysis of FUS.
Lund EM, Armstrong PJ, Kirk CA. 1992. Health status and population characteristics of dogs
and cats examined at private veterinary practices in the United States. J Am
Vet Med Assoc. 214:1336–41.
Mandelker L. 1995.What’s hot and what’s not. Vet Forum. 12: 54-55.
Marks SL, Straeter-Knowlen IM, Knowlen GG. 1993. The effects of phenoxybenzamine and
acepromazine maleate on urethral pressure profiles of anesthetized, health
male cats. J Vet Intern Med. 7:122.
Markwell PT. Buffington CT. Smith BHE. 1998. Effect of diet on lower urinary tract disease.
Diet and Lower Urinary Tract Diseases. The Journal of Nutrition. 128: 2753S-
2757S.
Martin SW. 1977. The evaluation of tests, Canadian Journal of Comparative Medicine 41: 19-
25.
Messing M. 1992. Interstitial cystitis and related syndrome. In: Campbell’s Urology. Walsh
PC, Retik AB, Stamey TA, editors. WB Saunders Philadelphia, USA. p. 982-
1005.
Milks H J. 1935. Urinary calculi. Cornell Vet. 25:153–161.
128
Muhammad G. Naureen A. Asi MN. Saqib M. Rehman FU. 2009. Evaluation of a 3% surf
solution (surf filed mastitis test) for the diagnosis of subclinical bovine and
bubaline mastitis. Tropical Animal Health and Production 42(3):457-464.
Naureen A. Saqib M. Muhammad G. Hussain M. Asi MN. 2007. Comparative evaluation of
Rose Bengal Plate Agglutination tests, mullein and some conventional
serological tests for diagnosis of spontaneous equine glanders. J Vet Diagn
Invest 19:362-367.
Norsworthry GD, Crystal MA, Fooshee FK, Tilley LP. 1998. The Feline Patient: Essential of
Diagnosis and Treatment. Williams & Wilkins Maryland USA. p. 210-214.
Osbaldison GW, Taussig RA. 1970. Clinical report on 46 cases of feline urological syndrome.
Vet Med Small Anim Clin. 64:461.
Osborne CA, Caywood DD, Johnston GR. 1991. Perineal urethrostomy versus dietary
management in prevention of recurrent lower urinary tract disease. J Small
Anim Pract. 32: 296-301.
Osborne CA, Johnston GR, Polzin DJ, Kruger JM, Bell FW, Poffenbarger EM, Feeney DA,
Stevens JB, McMenomy MF. 1984. Feline urologic syndrome: a
heterogenous phenomenon: J Amer Anim Hosp Assoc. 20:17–32.
Osborne CA, Kruger JM, Johnston GR, Polzin DJ. 1989. Feline lower urinary tract diseases. In:
Text Book of Veterinary Internal Medicine – Disease of Dogs and Cats.
Ettinger SJ, editor. 3th ed. WB Saunders Co. Philadelphia USA. p.2057-2082.
Osborne CA, Kruger JM, Lulich JP, JD Polzin, Lekcharoensuk C. 2000. Feline lower urinary
tract diseases. In: Text Book of Veterinary Internal Medicine – Disease of
129
Dogs and Cats. Ettinger SJ, Feldman EC, editors. 5th ed. WB Saunders Co.
Philadelphia. USA. p. 1710-1747.
Osborne CA, Kruger JM, Lulich JP. 1995. Feline lower urinary tract diseases. In: Textbook of
Veterinary Internal Medicine. Ettinger SJ, Feldman EC, editors. WB Saunders
Co. Philadelphia, USA. p. 1805-1832.
Osborne CA, Kruger JM, Lulich JP. 1996a. Prednisolone therapy of idiopathic feline lower
urinary tract disease: A double-blind clinical study. Vet Clin North Am Small
Anim Pract. 26:563-569.
Osborne CA, Lulich JP, Kruger JM. 1996b. Treatment of feline lower urinary tract disease by
debriding the bladder mucosa. Vet Clin North Am Small Anim Pract. 26:639-
642.
Parsons CL, Boychuk D, Jones S. 1990. Bladder surface glycosaminoglycans: An epithelial
permeability barrier. J Urol. 143:139-142.
Patronek GJ, Glickman LT, Beck AM. 1996. Risk factors for relinquishment of cats to an
animal shelter. J Am Vet Med Assoc 209:582–8.
Pereira DA. Aguiar JA, Michalik SJ. 2004. Changes in cat urinary glycosaminoglycans with age
and in feline urologic syndrome. Biochim Biophys Acta. 1672(1): 1-11.
Polzin DJ, Jenaj K. 1979. Urethritis, cystitis, ureteritis. Vet Clin North Am Small Anim Pract.
9:661-678.
Ratliffe TL, Klutke CG, McDougall EM. 1994. The etiology of interstitial cystitis. Urol Clin
North Am Small Anim Pract. 21:21-30.
130
Reif JS. 1983. Ecologic factors and disease. Textbook of Veterinary Internal Medicine.
Rich LJ, Kirk RW. 1969. The relationship of struvite crystals to urethral obstruction in cats. J
Am Vet Med Assoc. 154:153-157.
Roger AH, Chew DJ. 2005. Recent concepts in feline lower urinary tract disease. Vet Clin
Small Anml Practice. 35:147-170.
Ross LA. 1990. Treating FUS in a nonobstructed cats and preventing its recurrence. Vet Med.
85:1218.
Sant GR, Theoharides TC. 1994. The role of mast cells in interstitial cystitis. Urol Clin North
Am Small Anim Pract. 21:41-53.
Schechter RD. 1970. The significance of bacteria in feline cystitis and urolithiasis. J Am Vet
Med Assoc. 156:1567-1573.
Schechter RD. 1970. The significance of bacteria in feline cystitis and urolithiasis. J Am Vet
Med Assoc. 156:1567-1573.
Senior DF, Brown MB. 1996. The role of Mycoplasma species and Ureaplasma species in
feline lower urinary tract disease. Vet Clin North Am Small Anim Pract.
26:305-308.
Simons FE. 1992. The antiallergic effects of antihistamines (H1-receptor antagonists). J
Allergy Clin Immunol. 90:705-715.
Slater D. 1993. Textbook of Small Animal Surgery. Volume 2. 2nd ed. Philadelphia. WB
Saunders.
131
Sternberg EM, Chrousos GP, Wilder RL, Gold PW. 1992. The stress response and the
regulation of inflammatory disease. Ann Intern Med. 117:854-866.
Theoharides TC. 1994. Hydroxyine in the treatment of interstitial cystitis. Urol Clin North Am
Small Anim Pract. 21:113-119.
Thrusfield MV. 2007. Veterinary Thrusfield. 3rd ed. Blackwell synergy. USA.
Tomey SL and Follis TB. 1978. Incidence of Feline Urologic Syndrome in the United States.
Feline Pract. 8:39-41.
Van de Weerd HA, Docking CM, Day JEL, Avery PJ, Edwards SA (2003) A systematic approach
towards developing environmental enrichment for pigs. App Anim Beh Sci.
84: 101-118.
Van Rooijen J. 1991. Predictability and boredom. App An Beh Sci. 31:283-287.
Vet. Med. Assoc. 207: 1429–1434.
Viera AJ. Gerrat JM. 2005. Understanding interobserver agreement: the kappa statistic,
Family Medicine 37: 360-363.
Voros K, Wladar S, Marsi A, Vrabely T, Feyves B, Nemeth T. 1997. Ultrasonographic study of
feline lower urinary tract disease: 32 cases. Acta Vet Hungarica. 45: 387–
395.
Walker AD, Weaver AD, Anderson RS. 1977. An epidemiological survey of the feline urologic
syndrome. J Small Anm Pract. 18:283-301.
Westropp JL, Kass PH, Michalik SJ. 2006. Evaluation of the effects of stress in cats with
idiopathic cystitis. Am J Vet Res. 67(4): 731-6.
132
Westropp JL, Welk KA, Michalik SJ. 2003. Small adrenal glands in cats with feline interstitial
cystitis. J Urol. 170: 2494-7.
Wilkleberg P and Priester WA. Feline Urological Syndrome: Associations with some time,
space, and individual patient factors. Am J Vet Res. 37:975-978.
Willeberg P. 1975. A case control study of some fundamental determinants in the
epidemiology of the feline urologic syndrome. Nord Vet Med. 27:1-14.
Willeberg P. 1975. Outdoor activity level as a factor in the feline urologic syndrome. Nord
Vet Med. 27:523-524.
Willeberg P. 1981. Epidemiology of naturally occurring feline urologic syndrome. Vet Clin
North Amer Small Anim Pract. 4:455-469.
Willeberg P. 1984. Epidemiology of naturally-occurring feline urologic syndrome. Vet Clin N
Am Small Anim Prac 14:455–69.
