Feline Idiopathic Cystitis (FIC)

Feline Idiopathic Cystitis (FIC)

A noninfectious inflammatory and pain syndrome of the feline lower urinary tract associated with abnormal stress-response regulation

FIC is primarily a disorder of ______ rather than a disease of the bladder

abnormal systemic stress regulation

Feline idiopathic cystitis is the most common cause of...

irritative voiding in cats younger than 10 years!

Four reasons FIC is clinically important

1.) Most common cause of irritative voiding in cats younger than 10 years

2.) Common cause of inappropriate urination

3.) Important cause of urethral obstruction

4.) Major reason for shelter surrender

Two presentations of FIC

1.) Obstructive

2.) Nonobstructive

Five general causes of lower urinary tract inflammation

1.) Bacterial

2.) Fungal

3.) Viral (unproven)

4.) Chemical

5.) Idiopathic

The underlying cause of FIC is ultimately...

A sensitive cat in a provocative environment!

Some cats have an unusually sensitive stress response system, making them more likely to develop clinical signs when exposed to stressors

Five major components of FIC pathophysiology

1.) Abnormal central stress-response regulation

2.) Increased sympathetic activity

3.) Increased norepinephrine and altered α2-receptor responses

4.) Neurogenic inflammation

5.) Urothelial barrier dysfunction

Two major systems of the nervous system involved in the normal stress response

1.) Hypothalamic-pituitary-adrenal (HPA) axis

2.) Sympathetic nervous system

Hypothalamic-pituitary-adrenal (HPA) axis

major neuroendocrine pathway relevant to the stress response involving the hypothalamus, pituitary gland, and the adrenal cortex

Normal HPA-axis response to stress

Animal perceives stress → Hypothalamus releases corticotropin-releasing factor (CRF) → anterior pituitary releases Adrenocorticotropic hormone (ACTH) → adrenal cortex releases glucocorticoids

CRF

Corticotropin-releasing factor; hormone released by the hypothalamus that stimulates ACTH release and participates in sympathetic activation

ACTH

Adrenocorticotropic hormone; hormone released by the anterior pituitary that stimulates glucocorticoid production by the adrenal cortex

Normal function of glucocorticoids in the stress response

Provides negative feedback and help restrain excessive catecholamine activity

The sympathetic nervous system responds to stress by increasing ______ release

Catecholamine

Glucocorticoids normally ______ sympathetic activity. Why?

Restrain; they provide negative feedback that limits excessive or prolonged catecholamine responses

Six abnormalities of stress-response regulation in cats with FIC

1.) Decreased adrenal size

2.) Reduced ACTH responsiveness

3.) Downregulated HPA-axis activity

4.) Increased norepinephrine

5.) Increased sympathetic activity

6.) Reduced α2-receptor sensitivity

Adrenal gland size in cats with FIC

Decreased

Adrenal response to ACTH in cats with FIC

Reduced

HPA-axis activity in cats with FIC

Downregulated

Sympathetic nervous system activity in cats with FIC

Increased

Norepinephrine activity in cats with FIC

Increased

α2-adrenergic receptor sensitivity in cats with FIC

Decreased

Cats with FIC have increased sympathetic activity despite ______ HPA-axis activity. Why?

Decreased; impaired glucocorticoid-mediated restraint allows excessive sympathetic activation

Norepinephrine

Sympathetic neurotransmitter involved in stress responses and autonomic regulation

Normal function of α2-adrenergic receptors

Provide negative feedback on norepinephrine release and contribute to analgesic effects

Cats with FIC have ________ norepinephrine activity and _________ sensitivity of α2-adrenergic receptors

increased; reduced

Reduced α2-receptor sensitivity causes ______ norepinephrine activity. Why?

Increased; reduced negative feedback allows sympathetic stimulation to persist

Increased norepinephrine activity in FIC contributes to increased sensitivity to two stimuli

1.) Temperature

2.) Acidity

Neurogenic inflammation

Inflammation initiated or amplified by by activation of sensory nerves and release of neuropeptides

In FIC, abnormal sympathetic activity _______ sensory nerve stimulation within the bladder

increases

Four major components of neurogenic inflammation in FIC

1.) C-fiber activation

2.) Substance P release

3.) Mast cell activation

4.) Increased vascular permeability and inflammation

C fibers

Sensory nerve fibers involved in transmitting slow, poorly localized pain signals

C-fiber activity in cats with FIC

Increased sensitivity and stimulation; promotes release of inflammatory neuropeptides, particularly substance P

Neuropeptide released by activated sensory nerves in FIC

Substance P

Substance P

Neuropeptide involved in pain transmission and neurogenic inflammation

Four effects of substance P in FIC

1.) Increased vascular permeability

2.) Increased blood flow

3.) Activation of inflammatory pathways

4.) Increased pain sensitivity

Substance P contributes to ______ and ______ in the bladder

Pain; inflammation

Inflammatory cells activated during neurogenic inflammation in FIC

Mast cells

Function of Mast cells

release inflammatory mediators, including histamine, which can further stimulate sensory nerves and contribute to inflammation

Mast cell activation contributes to...

increased vascular permeability and local irritation through histamine

Neurogenic inflammation becomes self-perpetuating because...

sensory stimulation promotes inflammation, which further increases sensory stimulation

Neurogenic inflammation may contribute to urethral obstruction through...

Urethral smooth muscle contraction or spasm

Urothelium

Specialized epithelial lining of the urinary tract that protects underlying tissues from urine

Glycosaminoglycan (GAG) layer

Protective surface coating part of the urothelium that limits penetration of irritating urinary substances

Normal function of the GAG layer

Protects underlying bladder tissues and sensory nerves from urinary irritants

Two GAG abnormalities associated with FIC

1.) Reduced GAG quantity

2.) Altered GAG quality

Reduced/altered GAG can lead to...

increased urothelial permeability; this allows urinary constituents to interact more readily with underlying tissues and sensory nerve endings!!

Damage to the GAG layer causes increased ______ _______. Why?

Bladder irritation; urinary constituents can more readily penetrate the urothelial barrier and stimulate underlying sensory nerves

Four consequences of urothelial barrier dysfunction

1.) Increased sensory stimulation

2.) Pain

3.) Neurogenic inflammation

4.) Increased vascularity

Two possible cystoscopic findings in FIC

1.) Friable bladder lining

2.) Increased vascularity

Concentrated urine can worsen FIC signs because...

It contains higher concentrations of potentially irritating urinary substances

Since concentrated urine worsens FIC, what is an important component of managing FIC? Why?

Diluting urine; it decreases the concentration of urinary substances contacting the compromised urothelial barrier

FIC may be only one manifestation of a broader disorder called...

Pandora syndrome

Pandora syndrome

broader systemic disorder involving abnormal development or regulation of the stress-response system

Two broad factors potentially contributing to Pandora syndrome

1.) Genetic factors

2.) Epigenetic factors

Genetic factors associated with Pandora syndrome

Breed predispositions and familial patterns that may influence susceptibility

Epigenetic factors associated with Pandora syndrome

Environmental influences during critical developmental periods that alter stress-response regulation

*such as adverse early life experiences and perceived maternal stress

Three broad categories of systemic manifestations of Pandora syndrome

1.) Visceral

2.) Somatic

3.) Central

Visceral manifestations of Pandora syndrome

Abnormalities involving internal organs, including gastrointestinal, respiratory, cardiac, and urinary systems

Somatic manifestations of Pandora syndrome

Physical manifestations such as skin-related abnormalities

Central manifestations of Pandora syndrome

Behavioral abnormalities associated with altered central stress regulation

Two things FIC is not:

1.) Crystalluria

2.) Bacterial infection

Cats with FIC may have crystalluria because their urine is often...

Highly concentrated

However, crystalluria does not necessarily indicate that crystals are causing...

Bladder inflammation

Bacterial urinary tract infections become more common in ______ cats

Older

Antibiotics may appear effective in FIC even without bacterial infection. Why?

Most acute FIC episodes resolve spontaneously within approximately 7-10 days

Improvement following antibiotics does not prove...

Bacterial urinary tract infection

Urine pH and diet may influence urinary irritation and crystal formation but are not considered....

Primary underlying causes of FIC

Typical age range for FIC

1-10 years, especially 2-7 years

Sex distribution of nonobstructive FIC

Males and females affected approximately equally

Sex distribution when obstructive FIC is included

Males more commonly affected, approximately 2:1

Five common clinical signs of FIC

1.) Periuria

2.) Hematuria

3.) Pollakiuria

4.) Stranguria

5.) Dysuria

FIC may present with ______ as the only clinical sign

Periuria

Four clinical patterns of FIC

1.) Acute self-limiting

2.) Frequently recurrent

3.) Persistent FIC

4.) Urethral obstruction

Most common clinical presentation of FIC

Acute self-limiting episodes

Typical duration of an acute self-limiting FIC episode

Approximately 7-10 days

Frequently recurrent FIC

Repeated episodes of lower urinary tract signs separated by periods of improvement

Persistent FIC

Ongoing lower urinary tract signs rather than distinct self-limiting episodes

Three factors contributing to urethral obstruction in FIC

1.) Inflammatory plugs

2.) Urethral edema

3.) Urethral spasm

Urethral obstruction associated with FIC is particularly common in ______ cats

Male

Six characteristics/risk factors of the classic FIC patient

1.) Indoor-only

2.) Overweight or obese

3.) Approximately 2-7 years old

4.) Primarily dry diet

5.) Multicat household

6.) Sedentary

Multicat households may increase stress through...

competition for resources, including:

1.) Food

2.) Water

3.) Litter boxes

4.) Resting or hiding spaces

A cat may appear relaxed despite experiencing...

Chronic stress

Typical physical examination findings in uncomplicated FIC

Generally normal, although obesity may be present

Typical CBC findings in uncomplicated FIC

Normal

Typical serum chemistry findings in uncomplicated FIC

Normal

Four possible urinalysis findings in FIC

1.) Concentrated urine

2.) Hematuria

3.) Crystalluria

4.) Urine pH often below 7

Typical urine specific gravity in cats with FIC

Often greater than 1.035

Severe CBC or chemistry abnormalities in a cat with suspected FIC should raise concern for...

Another disease or complications such as urethral obstruction

FIC is a diagnosis of ______

Exclusion

Five important differential diagnoses for FIC

1.) Bacterial UTI

2.) Urolithiasis

3.) Urethral obstruction

4.) Neoplasia

5.) Anatomic abnormalities

Definitive diagnostic test for FIC

None; diagnosis requires exclusion of other causes of lower urinary tract disease

Three major management goals for FIC

1.) Reduce environmental stress

2.) Increase water intake and dilute urine

3.) Reduce urinary irritation

Most important long-term management strategy for FIC

Environmental modification!

Six environmental modifications that may benefit cats with FIC

1.) Elevated resting areas

2.) Hiding places

3.) Multiple food and water stations

4.) Adequate clean litter boxes

5.) Opportunities for play and hunting

6.) Visual enrichment

Recommended general litter box number in multicat households

One per cat plus one additional box

Providing multiple food, water, and litter box locations reduces...

Competition for resources and environmental stress

Increasing water intake helps manage FIC by...

Diluting urine and reducing the concentration of urinary irritants

Dietary strategy to increase water intake in cats with FIC

Increase moisture intake, often through wet food