Thursday, December 8, 2016

Lymph node enlargement in the cat.

Lymph Node Enlargement in the Cat

We’ve all heard of lymph nodes, but what exactly are they?  What do they do?  And why be concerned when they become enlarged?

            As a feline veterinarian, I perform dozens of physical examinations every week.  Every veterinarian performs the physical exam in his or her own style, making sure to evaluate all body systems thoroughly.  Assessment of the lymph nodes is unquestionably a part of every veterinarian’s physical exam. 

            The lymphatic system is an arm of the immune system that plays a role in the development of the body’s immune response. Lymph is the fluid that flows through the lymphatic system.  It is rich in protein and white blood cells.   Cells of the immune system circulate throughout the lymphatic vessels in the body. Lymph nodes are small, oval-shaped organs that make up part of the lymphatic system.  As lymph flows through the lymphatic vessels, it passes through at least one set of lymph nodes, and often several sets, before ultimately emptying into the general circulation where it mixes with blood.   The lymph nodes are the major sites in the lymphatic system where the immune cells gather.   

            Lymph nodes have a distinct anatomical structure, consisting of an outer portion called the cortex, and an inner portion called the medulla.  The cortex contains large numbers of lymphocytes, often arranged in clusters (follicles). There are two distinct types of lymphocytes found in lymph nodes: T lymphocytes and B lymphocytes. The B lymphocytes are responsible for producing antibodies, a process called “humoral immunity”.  T lymphocytes, once stimulated, are involved in a process called “cellular immunity”, the details of which are probably beyond the scope of this discussion.  The medulla contains lymphocytes as well as many other cells of the immune system, including macrophages and dendritic cells.  The entire lymph node is surrounded by a capsule comprised of connective tissue. 

            The immune system’s job is to protect and defend the body against harm by mounting an attack against invading substances (antigens).  When an antigen invades the body and makes its way to the lymphatic system and eventually to the lymph node, it stimulates a discrete population of lymphocytes in the node. This causes those lymphocytes to proliferate and transform, or become “activated”.  As noted above, activated lymphocytes may produce antibodies that neutralize the antigen, or the lymphocytes may become involved in more complex “cellular” immune responses.  When these lymphocytes proliferate, lymphadenopathy develops. Lymphadenopathy is the medical term for an increase in lymph node size.   Stimulation of the immune system is a common cause of lymph node enlargement.  Cancer is an equally common cause.

            Lymphadenopathy is sometimes noted as an incidental finding during physical examination of the cat.  Occasionally a cat owner will bring a cat to the veterinarian because of clinical signs related to the lymph node enlargement, for example, difficulty swallowing due to enlarged retropharyngeal lymph nodes (located at the back of the throat.  See sidebar.)  Sometimes a cat owner will bring a cat to the veterinarian because they’ve detected a lump, which turns out to be an enlarged lymph node, while patting or stroking the cat. 

            The age of the cat is important when considering the significance of lymph node enlargement.  Kittens and young cats are exposed to a variety of antigens early in their lives, and an increase in lymph node size is an expected response by the immune system.  As cats mature, lymph node size usually decreases and the nodes often become more difficult to palpate in older animals.  However, in geriatric cats or cats that have lost weight due to illness, the loss of body fat around the lymph nodes may make the lymph nodes appear more prominent than expected.

            Cancer, unfortunately, is a common reason for lymph node enlargement.  The size and texture of the lymph node may give clues in this regard.  Enlarged, firm, painless lymph nodes that are freely moveable is usually associated with primary lymph node cancer, i.e. lymphoma.  Very hard lymph nodes are more suggestive of metastatic cancer, i.e. a cancer arising in another site in the body that has spread to that lymph node.   The degree of enlargement may offer some clues as to the cause. Marked lymphadenopathy (the lymph node is 5 to 10 times the normal size) most often occurs with a lymph node abscess or with lymphoma; metastatic cancer rarely causes lymph node enlargement of this magnitude. 

            The location of the lymph node enlargement should also be considered in the patient evaluation.  If one lymph node is enlarged, or one regional group of lymph nodes is enlarged, one should carefully evaluate that area of the body for evidence of inflammation, infection, or cancer.  For example, if the right submandibular lymph node (the node just below the jaw) is enlarged, the right side of the mouth should be examined carefully.  A tooth root abscess involving a tooth on the right side, for example, could cause this nearby lymph node to be enlarged.   If, however, all of the lymph nodes involving the head region are enlarged, a more diffuse illness involving the head, such as an upper respiratory infection, would be something to consider.

            Obtaining a diagnosis in cases of lymph node enlargement may require a variety of tests, including blood and urine analysis, x-rays, and ultrasound.  Ultimately, a definitive diagnosis often requires obtaining a sample of cells from the node itself.  This is usually achieved either by aspiration cytology, or by surgical biopsy.

            Aspiration cytology is a procedure in which a needle, attached to a syringe, is inserted into the lymph node.  Suction is applied to the syringe so that cells from the lymph node are aspirated or sucked into the hub of the needle.  The contents are then sprayed onto a microscope slide and are sent to the laboratory for interpretation.  The advantage of this procedure is that it fairly non-invasive and inexpensive.  A disadvantage is that the aspirate may not yield enough cells to make a diagnosis.  Only positive findings are diagnostically useful.  The absence of abnormal findings in an enlarged lymph node means that the diagnosis is still unresolved. 

            Biopsy of the lymph node is the definitive diagnostic test in evaluating lymph node enlargement.  Depending on the size and location of the node, either the entire node is removed (this is called “excisional biopsy”), or a small piece of the lymph node is removed (this is “incisional biopsy”).  The biopsy specimen is then evaluated by a pathologist.  Treatment is based on the biopsy results: infections are usually treated with antimicrobials; cancer is treated by chemotherapy, surgery, radiation, or a combination of these.

            Lymph nodes are encapsulated structures containing aggregates of cells of the immune system that are capable of responding to a wide variety of invading antigens.  Enlargement of the lymph nodes occurs either due to reactive enlargement (stimulation of the immune system), primary cancer of the lymph nodes (lymphoma), or metastatic cancer.  Infectious causes of lymph node enlargement are more common in younger animals, while cancerous causes tend to be seen in older animals, although there is considerable overlap.  The size, location, and texture of the enlarged node(s) may offer clues as to the cause, and diagnostic tests such as x-rays, ultrasound, and blood and urine tests give valuable diagnostic information, however, obtaining a sample of the enlarged node is usually required for a definitive diagnosis to be achieved.

Sidebar: names and locations of some of the feline lymph nodes

Submandibular – just below the mandible (lower jaw)
Retropharyngeal – in the back of the throat
Cervical – in the neck, along the trachea
Axillary – in the armpit
Sternal – inside the chest along the sternum (breastbone)
Tracheobronchial – associated with the bronchi (airways) in the lungs
Sublumbar – above the colon, just below the spine
Inguinal – in the groin area
Popliteal – along the back of the thigh
Epigastric – adjacent to the stomach
Mesenteric – in the abdomen, associated with the intestines

Inflammation and enlargement of the lymph nodes is a common finding in companion animals.  Infection is a common cause of lymph node enlargement.  Cancer is also a common reason for lymph node enlargement.

Friday, November 25, 2016

Renomegaly - Enlarged Kidneys in Cats

Renomegaly in Cats

Renomegaly (enlarged kidneys) is a fairly common finding in cats.  This article discusses the common causes and potential treatments.

            I’m not the only veterinarian who has noticed that odd veterinary cases tend to come in twos and threes.   I can go months or even years without seeing a particular ailment, and then I’ll get two in the same week, sometimes even in the same day. 

            Last week I examined a 12 year-old cat for decreased appetite and weight loss.  From the cat’s scrawny appearance on the exam table, it was obvious that he had lost substantial weight.  On abdominal palpation, I immediately felt two markedly enlarged kidneys.   My very next appointment was a middle-aged cat for routine examination and vaccines.  The physical exam findings were normal, except when I felt the abdomen.  The right kidney was normal sized.  The left kidney, however, was at least three times the size of the right one. 

            Renomegaly (“reno” means “kidney”, “mega” means “increased size”) is the medical term for enlarged kidneys.  Renomegaly is not a diagnosis.  It is a physical exam finding.  Once identified, the judicious use of diagnostic tests such as x-rays, ultrasound, cytology, or biopsy often leads to a relatively quick diagnosis, because the list of disorders causing renomegaly in cats is fairly narrow. (see sidebar)  The characteristics of the kidney enlargement are helpful in formulating the list of possible causes. For example, renomegaly can be unilateral (one kidney affected) or bilateral (both kidneys affected).  It can be diffuse (the entire kidney is involved) or focal (only one part of the kidney is affected).  Renomegaly can also be described, based on the severity of the enlargement, as being mild, moderate, or severe.  

            Acute renal failure (ARF) typically causes bilateral, smooth, swollen painful kidneys.  Common causes include ingestion of toxins (with ethylene glycol or antifreeze being the most notorious), hypovolemic shock (inadequate perfusion of the kidneys), and pyelonephritis (bacterial kidney infection).

            Renal lymphoma is the most common cancer affecting the kidneys.  Affected cats are typically middle aged or elderly.  The degree of enlargement is moderate to severe, and both kidneys are involved.  Cats with renal lymphoma often have poor appetite, weight loss, excessive thirst and urination, lethargy, and pale gums. These signs are usually due to renal failure as a result of the lymphoma.  Some of these signs, however, may also be due to concurrent lymphoma in other organs such as the gastrointestinal tract and central nervous system.  Approximately 50% of cats with renal lymphoma are also infected with the feline leukemia virus.

            Feline infectious peritonitis (FIP) is an insidious viral disease that is nearly always fatal in cats.  Cats infected with FIP can develop either the “wet” form of the disease, in which the abdomen (and occasionally the chest cavity) fills with fluid, or the “dry” form, in which clusters of inflammatory cells, called granulomas, infiltrate various organs of the body.  The kidneys are a common target for these granulomas, and many cats with the dry form of FIP will have palpably enlarged, irregular kidneys.   There is no treatment for FIP, although an investigational drug called Polyprenyl Immunostimulant may show some promise in treating the dry form of the disease.  Further studies on this drug are needed.

            Sometimes, a cat will suffer some type of damage to one of the kidneys, resulting in a gradual loss of function in that kidney.  The loss of functional kidney tissue in the affected kidney continues over time, and the kidney gets smaller and smaller, as scar tissue forms in the kidney.  The cells of the opposite kidney become enlarged as the opposite kidney now has to do the work of both kidneys.  This enlargement is called compensatory hypertrophy and tends to be relatively mild.

            Polycystic kidney disease (PKD) is an inherited disorder in Persian cats and Persian crosses.  In cats with PKD, normal renal tissue is displaced by multiple enlarging cysts.   In most affected cats, clinical signs don’t develop until kidney failure develops, at which point the cat may show anorexia, increased thirst and urination, weight loss, and vomiting.  A more detailed discussion of polycystic kidney disease can be found in next month’s issue of Catnip (or whatever issue you decide to publish the article I’m scheduled to write).

            Primary renal cancer is uncommon in companion animals, accounting for less than 2.5% of all tumors in dogs and less than 1.7% of all tumors in cats.  As noted above, lymphoma is the most common renal cancer in cats.  It tends to affect both kidneys.  Other cancers affecting the kidney in cats include renal carcinoma, renal adenoma, and nephroblastoma.  These rare tumors are almost always unilateral.

            Renal abscesses and hematomas are uncommon causes of renomegaly in cats.  An abscess is a pocket of pus that develops within the kidney, either due to a blood borne infection, or via extension from an infected focus in a nearby organ.  Other causes include blunt abdominal trauma, penetrating wounds, or surgical contamination.  A hematoma is a solid swelling composed of clotted blood.  They usually occur secondary to trauma.

            Urine that is formed in the kidneys travels down the ureters into the bladder, and then out the urethra. If the flow of urine is obstructed, the urine builds up, causing dilation that begins in the central portion (the medulla) of the kidney.  The kidney tissue surrounding the medulla gets compressed from the pressure, until the kidney becomes a non-functional, fluid-filled sac, unless the obstruction is relieved.  Unilateral hydronephrosis results from obstruction involving a single ureter or kidney.  Common causes include a ureteral stone, a ureteral stricture, or accidentally tying off the ureter during spay surgery.  Cats that develop a stone in one ureter occasionally develop stones in the other ureter as well, which can lead to bilateral hydronephrosis.  The most common cause of unilateral hydronephrosis in cats is “idiopathic”, a nice way of saying that we have no idea why it happens.  Obstruction further down, at the level of the bladder or urethra, would be expected to cause bilateral hydronephrosis, however, even though urethral obstruction is very common in male cats, this obstruction is usually diagnosed quickly enough to precede any significant renomegaly. 
            [The kidney is surrounded by a tough fibrous capsule.  Occasionally, fluid can accumulate beneath the kidney capsule.  This will cause the kidney to feel enlarged on palpation.  Although these disorders technically are not causing enlargement of the kidney itself, they usually cannot be differentiated from true renomegaly based on abdominal palpation alone, or by x-rays.  Only by abdominal ultrasound can it be shown that the enlargement is due to the presence of fluid beneath the capsule of the kidney.  The most common sub-capsular disorders are sub-capsular hematomas and perinephric (perry-NEF-rick) pseudocysts.  Sub-capsular hematomas usually occur after blunt abdominal trauma or as a complication of kidney biopsy.  Perinephric pseudocysts  (“peri” = surrounding; “nephric” = pertaining to the kidney; “pseudo” = false) are accumulations of fluid just beneath the fibrous capsule that surrounds the kidneys.  They are called pseudocysts because they look like cysts, but unlike true cysts, they lack an epithelial lining.  One or both kidneys may be affected. Exactly why they develop is unknown.  About 75% of cats with perinephric pseudocysts also have some degree of chronic renal failure.] 

            As stated above, the list of causes of renomegaly is fairly narrow.  The age and breed of the cat is helpful in narrowing the list even further.  For example, young cats are more likely to have congenital problems or FIP.  Cancer is more common in older animals.  A high index of suspicion for PKD should be present if the patient is a Persian cat. 

            Physical exam findings also help narrow the list further.  Severe enlargement  is most likely caused by hydronephrosis, cancer, PKD, perinephric pseudocysts, or FIP.  If the kidneys feel irregular in shape, FIP, lymphoma, and other cancers are higher on the differential list.  Smooth kidneys are usually present in acute renal failure, hydronephrosis and compensatory hypertrophy.  If the cat shows pain when the kidneys are palpated, acute renal failure, kidney infection, and kidney abscess move up higher on the differential list. 

            Many of the illnesses that result in renomegaly will cause abnormalities on routine blood and urine tests. Occasionally, these tests alone will reveal the diagnosis.  In most cases, however, laboratory tests alone are inadequate for achieving a diagnosis for renomegaly.   X-rays give information about the size, shape and location of the kidneys, however, plain x-rays may not provide adequate detail.  A technique called excretory urography, in which a contrast agent is given intravenously, can enhance the appearance of the kidneys on the x-rays, giving more details regarding the cause of the renomegaly.   Ultrasound provides a rapid, non-invasive assessment of the kidneys, allowing evaluation of the internal structures of the kidneys.  Both techniques (x-rays and ultrasound) have their specific benefits and limitations. 

            In many cases, a definitive diagnosis for renomegaly requires obtaining a sample of the affected kidney tissue.  This is usually done either by a technique called fine-needle aspiration (FNA) or by biopsy.  Fine-needle aspiration is a procedure in which a needle, attached to a syringe, is inserted into kidney, using ultrasound guidance.  Suction is applied to the syringe so that cells from kidney are aspirated or sucked into the hub of the needle.  The contents are then sprayed onto a microscope slide and are sent to the laboratory for interpretation.  The advantage of this procedure is that it fairly non-invasive and inexpensive.  A disadvantage is that the aspirate may not yield enough cells to make a diagnosis.  If the aspirate doesn’t yield a diagnosis, a biopsy specimen needs to be obtained.  This can be done either through exploratory surgery, or less invasively through a variety of methods, such as laparoscopy (a procedure in which a fiber-optic device is inserted through a small hole in the abdominal wall, allowing a direct view of the abdominal organs), or through the use of a special biopsy needle, under ultrasound guidance, that allows for a small sample of kidney tissue to be obtained.  Once a diagnosis is obtained, a more specific treatment regimen can be devised.  Prognosis depends on the diagnosis.

            Renomegaly is not an unusual finding in cats.   A variety of conditions can lead to renomegaly, such as infiltration of the kidneys by inflammatory cells or cancer cells, structural abnormalities, hereditary conditions, and obstructive disorders.  Because the list of disorders causing renomegaly is narrow, veterinarians can often quickly arrive at a diagnosis, and treatment can be instituted. 

Sidebar: causes of renomegaly in cats

·      Acute renal failure
·      Lymphoma
·      Renal cancer (non-lymphoma)
·      Polycystic kidney disease (PKD)
·      Feline Infectious Peritonitis (FIP)
·      Compensatory hypertrophy
·      Renal abscesses and hematomas
·      [Perinephric pseudocysts]
·      Hydronephrosis

Sunday, November 13, 2016

Polycystic Kidney Disease

Polycystic Kidney Disease

            Polycystic kidney disease (PKD) is a slowly progressive inherited kidney disorder that affects Persian and Persian-related breeds.  It is the most prevalent inherited genetic disease in cats.  The prevalence of PKD varies in several countries, ranging from 36% (Slovenia) to 49.2% (United Kingdom).  In the United States, the prevalence of PKD in Persian and Persian-related cats is approximately 38%

            Although most normal cats eventually develop signs of kidney disease as they age, cats with PKD experience the signs of chronic kidney disease (CKD) at an earlier age.  Typically, cats begin to show the first signs of CKD around the age of 13 or 14.  Cats with PKD, on average, will develop signs of CKD around 7 years of age. 

            The job of the kidney is to filter toxins from the bloodstream and put them into the urine.  As cats age, normal kidney tissue is slowly replaced by scar tissue, and the kidneys gradually become less effective at filtering.  As the scar tissue contracts, the kidneys become progressively smaller in size.  The kidneys of cats that are affected by PKD also gradually lose their ability to filter, however, the kidneys of these cats become enlarged rather than become smaller.  This is due to the existence of multiple cysts (hence the “polycystic” in the name) that are present in both kidneys at birth. The cysts grow slowly over time, causing the kidneys to enlarge. These cysts compress the kidney tissue surrounding them, reducing their function.  The cysts can vary in size from less than 1 mm to greater than 1 cm.  Because the cysts enlarge over time, older cats will have larger cysts.  Cats with PKD occasionally will develop cysts in the liver as well, although this has no clinical consequence.

            The signs of CKD in cats include increased thirst and urination, poor appetite, weight loss, vomiting, and lethargy. Blood and urine tests will confirm that a cat has chronic kidney disease, but they do not establish that PKD is the underlying cause.  Late in the course of the disease, the detection of enlarged, irregular kidneys in a Persian or Persian-related cat is certainly suggestive that PKD is present, however, early in the course of disease the cysts are not detectable on physical examination.  To make a diagnosis of PKD early in the course of a cat’s life, some sort of diagnostic imaging procedure will need to be employed, with ultrasound being the most sensitive and noninvasive technique for this.

            Ultrasound has the potential to detect PKD very early in the course of disease, i.e. as early as 6 to 8 weeks of age.  In some instances, cysts have been detected in kittens as young as 4 weeks old.  In the hands of an experienced ultrasonographer, PKD can be diagnosed with approximately 75% sensitivity in cats less than 16 weeks of age.  This increases to 91% sensitivity in affected cats at 36 weeks of age (because the cysts may be larger and easier to detect). 

            In Persian cats, PKD is inherited as an “autosomal dominant” trait.  This means that if a cat with PKD is bred to a normal cat, 50% of the offspring will develop PKD.  Because kidney disease resulting from PKD develops later in life, an affected cat may have been used to produce a large number of kittens before it becomes ill from PKD itself.  Fortunately, PKD can now be diagnosed via genetic testing.  The test requires submitting a cheek swab or a blood sample to an appropriate testing facility.  When performing the genetic test, cats of any age can be tested. However, if testing kittens that have not yet been weaned, a blood sample is necessary, since nursing kittens will have traces of the mother cat’s DNA in their mouths, which may lead to inaccurate results if using a cheek swab. The genetic test accurately identifies all cats carrying the abnormal gene.

            Early identification of PKD, whether through ultrasound or genetic testing, is helpful because it allows the detection of the disorder before cats are bred.  If all affected cats are neutered and spayed once the disorder is detected, PKD could be eliminated completely from breeding populations.  Anyone planning to purchase a Persian kitten from a breeder should ask the breeder to give proof that the cats used to produce the kitten were screened as negative. 

            There is no treatment for PKD per se.  Treatment of the chronic kidney disease that results from PKD is similar to that of cats that develop CKD as a result of the natural aging process, or of any other cause of CKD.  This may include subcutaneous fluid administration, potassium supplementation, phosphorus binders, anti-nausea medications, appetite stimulants, drugs to control elevated blood pressure, drugs to reduce excessive protein loss in the urine, and the feeding of prescription diets that have reduced levels of protein and phosphorus.  Although there is no specific treatment for PKD, the presence of PKD can be reliably demonstrated by ultrasound in an older cat, or via genetic testing in any age cat.  If breeders remove all affected cats from their breeding stock, it should be possible to eradicate the disease from the breed.



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