Sharpen your veterinary skills

Mini Veterinary School

Teaching case for wanna be veterinarians. 

If you enjoy figuring out  veterinary medical puzzles, we have a treat for you. 

We will give you a chance to test your medical skills. 
Answer the questions honestly, and don't peek at the answers. 
There is 15 available points if you answer all the questions correctly. 

Vinnie Bag of Donuts

We met Vinnie  on September 26^th.  He is a 9yr old  neutered male indoor-only Maine Coone who had been overweight all his life. 

Presenting  complaints: 

Weight loss of  3-4 weeks duration.
Complete loss of appetite for three days, vomiting for a day.

Vinnie's  Diet : Dry. (Ingredients: http://www.hillspet.com/products/sd-feline-adult-indoor-dry.html)

Symptoms and Examination findings: 

Marked depression / loss of energy

Loss of appetite

Weight loss

Nausea and vomiting

Drooling / hyper salivation

Moderate Dehydration

Yellowing of the whites of the eyes and skin

Enlargement on  cranial abdominal palpation
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What tests  would you order? 

a) EKG
b) urinalysis
c) blood test + urinalysis
d) X-ray
e)blood test

Give yourself 2 points if you answered c) blood test + urinalysis and scroll down to read the results.

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WBC	12.2	4.2 - 15.6 K/uL
RBC	6.05	6.0 - 10.0 M/uL
HGB	8.1	9.5 - 15 g/dL	LOW
HCT	25.1	29 - 45 %	LOW
MCV	42	41 - 58 fL
MCH	13.4	11.0 - 17.5 pg
MCHC	32.3	29 - 36 g/dL
% RETICULOCYTE	0.3	%
RETICULOCYTE	18	3 - 50 K/uL
RETICULOCYTE COMMENT	A reticulocyte count of greater than 50 K/uL of blood is considered evidence of bone marrow response to an increased peripheral demand. Depending on the degree of anemia, a reticulocyte count <50 K/uL may indicate an inadequate bone marrow response. Serial monitoring of the erythrogram and absolute reticulocyte count may be useful to evaluate bone marrow responsiveness over time. The following chart can be used as a guideline to determine appropriateness of regenerative response. Degree of bone marrow response (K/uL): Mild 50-75 Moderate 75-175 Marked >175 Please note: For information about our new reticulocyte reporting, please see the Diagnostic Update on Vetconnect.com or call the internal medicine consulting team at 1-888-433-9987, option 4, option 2.
NEUTROPHIL SEG	85.0	35 - 75 %	HIGH
LYMPHOCYTES	9.0	20 - 55 %	LOW
MONOCYTES	4.0	1 - 4 %
EOSINOPHIL	2.0	2 - 12 %
BASOPHIL	0.0	0 - 1 %
AUTO PLATELET	547	170 - 600 K/uL
REMARKS	NO FELINE HEMOTROPIC MYCOPLASMAS (FHM, formerly Hemobartonella) seen. IF FHM IS SUSPECTED, THE IDEXX RealPCR FOR FHM IS MORE SENSITIVE THAN BLOOD FILM REVIEW. UNIT CODE 1717. SLIDE REVIEWED MICROSCOPICALLY.
ABSOLUTE NEUTROPHIL SEG	10370	2500 - 12500 /uL
ABSOLUTE LYMPHOCYTE	1098	1500 - 7000 /uL	LOW
ABSOLUTE MONOCYTE	488	0 - 850 /uL
ABSOLUTE EOSINOPHIL	244	0 - 1500 /uL
ABSOLUTE BASOPHIL	0	0 - 100 /uL
TOTAL HEALTH PLUS AND FREE T4 : FREE T4
Test	Result	Reference Range		Low Normal High
FREE T4 (ng/dL)	0.6	0.7 - 2.6 ng/dL	LOW
FREE T4 (pmol/L)	7.7 1	9.0 - 33.5 pmol/L	LOW
Comments: 1. In middle-aged to older cats with clinical signs of hyperthryoidism and a total T4 in the "grey zone" or upper end of the reference interval, an increased free T4 supports the diagnosis of hyperthyroidism. A normal free T4 makes the diagnosis of hyperthyroidism unlikely, but if a strong clinical suspicion remains, repeat thyroid testing in 6 to 8 weeks or a technesium scan is indicated. Please note: The reference interval has been updated based on results of a clinical trial using a new free T4 test.

ALK. PHOSPHATASE	498	0 - 62 U/L	HIGH
ALT (SGPT)	37	28 - 100 U/L
AST (SGOT)	38	5 - 55 U/L
CK	158	64 - 440 U/L
GGT	2	0 - 6 U/L
AMYLASE	1295	520 - 2060 U/L
LIPASE	21	10 - 195 U/L
ALBUMIN	3.4	2.3 - 3.9 g/dL
TOTAL PROTEIN	7.1	5.9 - 8.5 g/dL
GLOBULIN	3.7	3.0 - 5.6 g/dL
TOTAL BILIRUBIN	6.3	0.0 - 0.4 mg/dL	HIGH
DIRECT BILIRUBIN	6.0	0.0 - 0.2 mg/dL	HIGH
BUN	20	15 - 34 mg/dL
CREATININE	1.3	0.8 - 2.3 mg/dL
CHOLESTEROL	146	82 - 218 mg/dL
GLUCOSE	103	70 - 150 mg/dL
CALCIUM	9.7	8.2 - 11.8 mg/dL
PHOSPHORUS	4.2	3.0 - 7.0 mg/dL
TCO2 (BICARBONATE)	17	13 - 25 mEq/L
CHLORIDE	116	111 - 125 mEq/L
POTASSIUM	4.7	3.9 - 5.3 mEq/L
SODIUM	153	147 - 156 mEq/L
A/G RATIO	0.9	0.4 - 0.8	HIGH
B/C RATIO	15.4
INDIRECT BILIRUBIN	0.3	0 - 0.3 mg/dL

URINALYSIS ADD-ON
Test	Result	Reference Range		Low Normal High
COLLECTION METHOD	NOT GIVEN
COLOR	DARK YELLOW
CLARITY	TURBID
SPECIFIC GRAVITY	1.036
GLUCOSE	NEGATIVE
BILIRUBIN	3+		HIGH
KETONES	NEGATIVE
BLOOD	3+		HIGH
PH	6.5
PROTEIN	TRACE (<100 mg/dL) 1
WBC	0-2	0 - 5 HPF
RBC	20-30	0 - 5 HPF	HIGH
BACTERIA	NONE SEEN	HPF
EPI CELL	1+ (1-2)	HPF
MUCUS	NONE SEEN
CASTS	NONE SEEN	HPF
CRYSTALS	2+ BILIRUBIN (3-5)
OTHER	AMORPHOUS DEBRIS PRESENT
UROBILINOGEN	NORMAL

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With what you know so far about Vinnie and with these lab results do you suspect that he has:

a)  kidney infection
b) thyroid disease
c) pancreatitis
d) liver disease
e) liver disease and anemia

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Diagnosis

Elevated alkaline phosphatase, a liver enzyme indicative of damage of the cells surrounding the bile ducts. 
Elevated bilirubin is a marker of jaundice (yellowing of skin and gums), but unfortunately it takes a marked elevation and advanced disease for the skin to become obviously yellow.
Bilirubin in blood ( bilirubinemia) and 

Bilirubin in  urine ( bilirubinuria) confirm that Vinnie was suffering from  hepato-biliary disease.  In cats, unlike dogs, any bilirubin in the urine is abnormal.

Anemia ( low Red Blood Cells) are indicated by low Hematocrit ( HCT similar to PCV) and HGb ( hemoglobin)


There are other causes 
of elevated alkaline phosphatase : such as rapid bone turn-over in young growing patients,
 as well as elevated bilirubin : hemolysis 
you can read about here ---> http://www.vetmed.wsu.edu/cliented/lab.aspx


 In determining the likely origin of elevated tests we look at the "whole picture"--the entirety of all the tests and the clinical picture of the patient, to arrive at the most likely cause. 

If you said d) liver disease (hepatopathy), give yourself 2 points

if  you said e) liver disease (hepatopathy) and anemia give yourself 4 points

The liver is an organ with hundreds of jobs. Some of the more important ones are

• Production of bile needed to digest fat, and storing it in the gall bladder.
• Production of  vital proteins- albumin and clotting factors. Conversion of hormones.
• Storage of glycogen ( a starchy form of sugar) and converting it back into sugar when the need for energy arises.
• Storage of red blood cells and iron for hemoglobin, and clearance/ recycling  of worn out red blood cells.
• Packaging of amino- acids (building blocks of proteins), fatty acids,  triglycerides, cholesterol.
• Bacteria of the bowels produce ammonia as they break down proteins, which the liver converts into a less toxic substance called urea ( BUN) which is excreted by the kidneys in the urine.
• Clearing blood of toxins, drugs and anesthetics
• Storage of fat soluble vitamins: A, D, E, K.
• Filtering bacteria from the small intestines

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What test would you order at this point?

a) x-ray
b) ultrasound with ultrasound-guided fine needle aspirate (FNA)
c) barium study
d)exploratory abdominal surgery
e) ultrasound

avetsguidetolife.blogspot.com

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If you said ultrasound, give yourself 2  points
if you said ultrasound with  ultrasound-guided FNA, give yourself 4 points

Vinnie’s ultrasound ruled out many underlying illnesses while confirming our suspicion of an 
enlarged liver. Unlike an Xray which shows outlines of organs, an ultrasound can image soft tissue organs in three dimensions enabling us to see the texture and dimensions of all soft tissue organs--liver, kidneys, spleen, pancreas, intestines, lymph nodes, adrenal glands,  as well as to evaluate organs in motion ( which is especially important for studies of the heart). An Xray would have just shown us that Vinnie's liver was enlarged, bout would not enable us to know the condition of the rest of the organs. This test is not uncomfortable and does not require anesthesia. 

A fine needle aspirate (FNA) was performed with ultrasound guidance. This is a noninvasive test in which liver cells are harvested with a syringe and examined on a slide. The technique, known as cytology is not as conclusive as histopathology or  biopsy, because we examine individual cells and are unable to see how they are arranged. Although not without limitation, cytology  unlike biopsy does not require general anesthesia thereby involving much less risk, as well as costs. 

Cytology confirmed hepatic lipidosis ( steatosis) -infiltration  and distention of liver cells with large fat vacuoles (the foamy cells seen are vacuolated hepatocytes)

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If Vinnie could only have ONE thing, what is the single most important treatment Vinnie must have to overcome his disease?

a) antibiotics and anti-inflammatory drug injections
b) IV fluids and nausea drugs
c) herbs and supplements to help his liver
d) implantation of a feeding tube for aggressive nutritional support
e) liver transplant

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Treatment

Vinnie was hospitalized and was given intravenous fluids and medications to control nausea. The medications he was given are listed below with links for more thorough understanding and reasoning behind each

Rx:

• SAM-E

http://www.lef.org/magazine/mag97/june-report972.html

• Milk thistle:

http://www.veterinarypracticenews.com/vet-practice-news-columns/complementary-medicine/milk-thistle-shows-promising-applications-in-treating-liver-disease-cancer.aspx

• Vitamin E

 http://www.cbsnews.com/2100-204_162-6443900.html

• Ondasetron:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000157/

• Reglan:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000132/

• Arginine:

http://jpet.aspetjournals.org/content/299/3/832.full

http://www.ncbi.nlm.nih.gov/pubmed/8878148

• Ursodiol

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001055/

• Vitamin B

A feeding tube was implanted in his esophagus, which enables aggressively feeding him in spite of him not being interested in eating at all.  The feeding tube also enables easy administration of his medications. It is difficult, if not impossible, to force- feed these patients adequate calories and nutrients to reverse the disease without a feeding tube.

Feeding: 
Each day the owner places a can of Science Diet A/D  in a blender and blenderize it into a slurry which is easy to administer through the tube.
http://www.hillspet.com/products/pd-feline-ad-caninefeline-critical-care-canned.html

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If you answered feeding tube give yourself 5 points. 

 Without aggressive  nutritional support it is difficult , if not impossible, to force-feed these patients adequate calories and nutrients to reverse the abnormal metabolic cycle. 

Considering how Vinnie looked a couple of weeks ago, we are pleased with his progress. He is acting more and more like himself every day. Yesterday his mom said he begged for treats for the first time in a long time.

Hepatic lipidosis (HL)  is one of the most common of all cat liver diseases, affecting cats of any age, breed and sex.  Overweight cats are at increased risk of developing HL. Rapid weight loss, loss of appetite, starvation and catabolism are the initiating cause of fat infiltrating the liver.   

Similar disease is seen in birds, rabbits, mustelids (mink, ferrets), as well as people in whom it is known as Non-alcoholic fatty liver disease (NAFLD). 

Anorexia (loss of appetite) can be caused by changes in diet,  stress, and the underlying disorders listed below.  Inflammatory bowel disease (IBD) is  frequently associated with hepatic lipidosis.

Other liver disorders:	Small intestinal diseases:
Cholangiohepatitis	Eosinophilic enteritis
Choledochitis	Lymphocytic/plasmacytic enteritis
--extrahepatic bile duct obstruction	Chronic bowel obstruction
Chronic suppurative hepatitis	Salmonella enteritis
Portosystemic vascular anomaly
Bile duct adenocarcinoma	Renal disorders
Hepatic lymphosarcoma	Chronic FUS
Neoplasia (non-hepatic):	Pyelonephritis
Urinary bladder	Chronic interstitial nephritis
--transitional cell carcinoma	Hyperthyroidism
Metastatic carcinoma	Severe Anemia
Intestinal adenocarcinoma	Pyometra
Intestinal lymphosarcoma	Cardiomyopathy
Pancreatitis	Central neurologic disease
Diabetes mellitus

In many cases no underlying cause can be identified and then the disorder is called idiopathic hepatic lipidosis. 

Since we found no underlying cause for Vinnie's hepatic lipidosis, his form of liver disease is termed idiopathic hepatic lipidosis.

 The rapid development of hepatic lipidosis in obligate carnivores during fasting could be related to depletion of arginine (an amino acid/ building block of proteins) and the loss of muscle mass due to reliance on gluconeogenesis (http://en.wikipedia.org/wiki/Gluconeogenesis ) for blood sugar provision during food deprivation. Other explanations are altered omega-6 to omega-3 fatty acid ratio and oxidative stress. Mobilization and accumulation of fat in the liver impairs liver function until the liver fails.

If not recognized promptly and treated aggressively, the patient would progress to stupor, seizures, coma, internal bleeding and death.

Fortunately for us Vinnie is getting better. As of yesterday he is no longer nauseous and is beginning to show interest in treats. We are hoping to be able to remove the esophageal feeding tube within a few weeks.

 Once he is eating voluntarily we will feed him a meat- only diet, free of grains; especially avoiding the genetically modified corn, whose safety studies leave me entirely unimpressed.

In fact, these exact histopathological findings are reported in the majority of the rats in this study on Bt corn ( Mon 863), Table 7: Liver Vacuolization 17/20 male control rats  20/20 male rats fed this genetically modified corn,  18/20 female rats fed control corn and  20/20 female rats fed the gentically modified corn.

Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn

B. Hammond a,*, J. Lemen a, R. Dudek a, D. Ward a, C. Jiang a, M. Nemeth a, J. Burns b

Clearly this variety of corn with or without genetic modification causes  liver changes in mammals.  It is impossible to tell how much the genetic modification itself contributes to liver toxicity of this corn with a group this small. And I find it curious that in this experiment 80 rats were fed the genetically modified variety but results are only published for 40--this renders any statistical analysis invalid.

Additionally liver toxicity  on the nuclear cellular level leading to alteration of protein expression, related to splicing structures in rodents is associated with  genetically modified soybeans as extensively documented by Manuella Malatesta. 

Histochem Cell Biol. 2008 Nov;130(5):967-77. Epub 2008 Jul 22.

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing.

Malatesta M, Boraldi F, Annovi G, Baldelli B, Battistelli S, Biggiogera M, Quaglino D.

Source

Dipartimento di Scienze Morfologico-Biomediche, Sezione di Anatomia e Istologia, University of Verona, strada Le Grazie 8, 37134, Verona, Italy. manuela.malatesta@univr.it

Abstract

Liver represents a suitable model for monitoring the effects of a diet, due to its key role in controlling the whole metabolism. Although no direct evidence has been reported so far that genetically modified (GM) food may affect health, previous studies on hepatocytes from young female mice fed on GM soybean demonstrated nuclear modifications involving transcription and splicing pathways. In this study, the effects of this diet were studied on liver of old female mice in order to elucidate possible interference with ageing. The morpho-functional characteristics of the liver of 24-month-old mice, fed from weaning on control or GM soybean, were investigated by combining a proteomic approach with ultrastructural, morphometrical and immunoelectron microscopical analyses. Several proteins belonging to hepatocyte metabolism, stress response, calcium signalling and mitochondria were differentially expressed in GM-fed mice, indicating a more marked expression of senescence markers in comparison to controls. Moreover, hepatocytes of GM-fed mice showed mitochondrial and nuclear modifications indicative of reduced metabolic rate. This study demonstrates that GM soybean intake can influence some liver features during ageing and, although the mechanisms remain unknown, underlines the importance to investigate the long-term consequences of GM-diets and the potential synergistic effects with ageing, xenobiotics and/or stress conditions.

Since no epidemiological studies have been published to date comparing cats eating GMO- corn and soybeans with non-GMO- corn and soybeans, the precautionary principle dictates avoiding  corn  and soy in cat foods.

 We hope you did well on the quiz and enjoyed the learning experience. 

Give yourself an A if you scored 15 points, a B if you scored 11, a C if you scored 10 or less.
Feel free to ask questions or leave comments, if you like. 

References:

Treatment for Severe Feline Hepatic Lipidosis

Sharon A. Center, DVM, DACVIM College of Veterinary Medicine, Cornell University

http://www.2ndchance.info/oldcatcenter2005.pdf

http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2006&PID=15828&O=Generic

http://jn.nutrition.org/content/128/12/2747S.short

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.1993.tb01008.x/abstract

Fatty Acid Composition and Development of Hepatic Lipidosis During Food Deprivation—Mustelids as a Potential Animal Model for Liver Steatosis http://ebm.rsmjournals.com/content/234/3/278.full

http://www.ncbi.nlm.nih.gov/pubmed/12441651

http://www.ncbi.nlm.nih.gov/pubmed/18648843

http://www.ncbi.nlm.nih.gov/pubmed/12448776

http://www.ncbi.nlm.nih.gov/pubmed/16216809

December 11,2012 Update

 Vinnie developed an abscess at the esophageal tube site, and it  had to be removed. 
Like many dry- food junkies addicted to  carbohydrates, the texture and shape of the kibble Vinnie  refuses to eat sufficient quantities of  canned meat to sustain himself. 
 It is often very challenging to switch junk-food junkies to healthy foods.
Given the choices we elected to allow him to eat what he will for the time being. The owner  will have to deal with the challenge of switching him to a more appropriate food  later.