Occurrence, Etiology, Pathogenesis, Diagnosis and Treatment of Liver Diseases in Cattle

"Occurrence, etiology, pathogenesis, diagnosis and treatment of liver diseases in cattle"
Dr. med. vet. Manfred Fürll
University of Leipzig, Department of Animal Husbandry and Veterinary Medicine
Department of Internal Medicine and Pathophysiology
Objective
Milk reduction and health disorders in dairy cows are frequently discussed in connection with an overload of the liver function. Macroscopically visible changes in this organ slaughtered sick, but also in normally slaughtered cows seem to support this view.Asfor examplefrom 1950with1851 kgto 1985with 4370kg (3.5% fat) the average annualmilk yieldofcowsin East Germanymorethandoubled, high-yielding cows even reached7255 kg, is as a consequence of thisdevelopmentandtheassociated requirementsin some casesnon-criticalfastto aclosedliver failure, especially ifadditionaldeficitsof the feed are present.

A clinicalobjectificationof theliverconditionisgenerallydifficult andkeptthelittlepromising fortherapeutical response. Fromthis situation, thetaskwas derived
- The currentincidence ofliverdamagein cattletodetectand analyze

-Toinvestigatethe importanceofbutyric acidinfluence,ofperipartalfeeding,fastenand amedicatedstimulatedlipolysisin the developmentofliverdamage and the developmentof pathologicalprocesses

-Toobjectifythe diagnosis ofliverdamagewhen taking into accountaspectsofthe veterinary practiceand
- Possibilities forpharmacologic agentsinfluencingthe liverand selectedspecimenstocheck forliver-damagingeffects
Focusonthe processingformed thelipidaccumulationthanthe commonestliverimpairment,and thefree fatty acid(FFA) in blood andtheirrelationshiptothe criteria ofliverfunction.

Materials and Methods
The occurrence of liver damage was analyzed in
- peripartal 2 dairy farms (A and B) at 22 resp. 18 cows with an annual milk yield 4500 and 5350 kg FCM
- For 5-year metabolic control according to TGL 34 313 in one district in cows 2-8 weeks p. p. (post partum) with a milk yield between 3500 and 5000 kg FCM
- In 336 cattle at theDepartment of Internal Medicine and Pathophysiology
in the years 1978 to 1987
- At 941 and ill-slaughtered cattle (895 cows, 46 bulls) in two sanitary slaughterhouses (A and B SSB)
with clinical chemistry (mainly bilirubin and AST in the blood and liver lipids) and partly histological methods.

The aetiology and pathogenesis of liver damage occurred in studies
- Subacute butyric acid burden intraruminal (0,5 -, 1,0 -, 2,0 g / kg BW) in 42 cattle
- 95 cows in the peripartal period with different feeding, namely
• high energy in the dry period (ap), as required p. p.
• a high energy a.p., energy-reduced p. p.
• energy-reduced from 4-2 weeks ap, p.p. as required
• according to the instructions of the GDR feed evaluation system
- 10 cows and sheep for 3 -, 10 - and 12-day food deprivation as well as
- Intravenous epinephrine administration (3 cows, 0.5 mg/100 kg BW)
by complex clinical-chemical and histological analysis with emphasis on liver lipids and FAA, bilirubin, AST, ketone bodies and glucose in the blood, including further criteria of carbohydrate, fat, protein and mineral metabolism, acid-base balance, and hormones.

Thediagnosis ofliverdamagehas been checkedby
-Methodologicalstudies on thediurnal variation ofFFAandthe influenceofadrenalineapplication(9 and6 cattle)
- Comparisonbetween indirect(floating liversample) anddirectdetermination ofliverlipid(59cows)
- Analysisof variousliverfunction andmetabolicparameters in theperipartalperiod (40 cows)
- Analysis of thefindingsof 101ill-slaughteredcows.

The focus was ontheliverlipids, andthe diagnosticinformations of theFFA inrelationtootherclinical-chemical andhistologicalparameters.

Aliver-sparing effect ofnicotinic acidwasat20 cowsat 3days offood deprivation(5 and10 g/d) and at 35 cowsperipartal 1 weekapand 2weeks p. p. at different dosesandin some casesenergyrestriction, forBilliton® (dehydrocholic acid) (5.5 g/d) for 9cowsperipartal and for 5sickcattletested.

Theexamination of potentialliver-damaging effectsof ACTH(0.5,0.6 and1.0 IU/ kg body weight) andglucocorticosteroids(Prednisolut ®- 0.5mg/kg FM; prednisolone0.2,04 and0.6 mg/kg BW) was performed inone-andfive-dayperipartalapplicationon 10 sheepand 26cows, and for phenylbutazone® (5g/d) on 5 cows. Theanalytical methods usedforproof of efficacyincludedclinical-chemical complexcriteria, andperformance parametersinperiparturientandin some caseshistologicaldiagnostic findings.
Fromthe obtainedresults suggestthe following

conclusions:

1.Liverdamageis dominatedbycows inearly lactationphaseand additionallyexited thewinter feeding. Ketosis, birth and puerperaldisorders, inflammatory processesandindigestionareoften accompanied byliverdamage.Therefore,thefeeding and managementofhighlypromisingandfreshlycalvedcows, thelatewinter feedingand the preventionof thediseasesmentioned aboveandfor the preventionofliverdamage, special attention hasto beconsidered.

2. Investigationsintotwofarms according to thefatty liveroccursin 27% and 56% of dairy cows(4500, 5350 kg FCM) 1 to 4 weeks p. p. before. During the sameperiodareabnormalASTactivities andbilirubin concentrationsat 41% and 56% of the cows.Their shareis reduced(21% and 24%) when the studyperiodup to 8weeks p. p. isextended.

3. In the past 20 years, a shift in the frequency of disease is observed with liver damage. Hemolytic anemia occur less often. Almost half of the sick cow slaughtered has a macroscopically abnormal liver. In them, clearly outweighs the fatty liver (55%) compared with reactive-inflammatory (29%) and degenerative processes (16%).

4. The main cause of increased lipid concentrations in the liver of dairy cows p. p. is an energetic overfeeding during the dry period. The lipid content of liver increases even further if these cows beforeparturition are no longer supplied sufficient energy. Therefore, the major route for the prevention of postpartal fatty liver in the feeding of dairy cows according to the instructions of the GDR feed evaluation system can be seen.

5. Three-week butyric acid exposure does not cause liver damage. To considerable accumulation of fat in the liver it is however if cows 3 days the food is removed. The quality of reduced when fed silage often observed liver damage have therefore not directly their cause in the high butyric acid content, but due to other factors, which include among other things, to the energy supply is insufficient. Also assist in the prevention of liver damage in the production of high quality silage all the attention has to apply.

6. The pathogenesis of postpartal fatty liver is preceded by a rise in concentration of FFA. They reach their maximum 1 week p. p. which is earlier than the liver lipids. Conversely, following the decline in FFA levels and a decrease in liver lipid concentration. With food deprivation, the lack of energy consumption is displayed quickly by a sharp increase in the concentration of FFA.

7. For lack of energy is a secure relationship (p ≤ 0.01) between FFA and bilirubin. Such is also when the FFA concentration was increased by i.v. adrenaline administration. This causal relation is interpreted in the literature with the competition of both metabolites by a microsomal transport protein in liver cells.

8. In energy lack situations (postpartum, food deprivation) occur regularly increasing ß-OH-butyrate (BHB) concentrations. They are compared with the increase in FFA at different times and be accompanied by glucose concentrations in blood plasma up to the lower boundary as a sign of carbohydrate depletion.

9. The activity of AST is by postpartal puerperal influences (caruncle degradation, etc.) and body mass loss (protein degradation in muscle cells), but increased with food deprivation. The postpartal existing secured relationship between AST activity and liver lipid concentration are indirectly. AST activities and BHB concentration does not move regularly compliant.

10. Clinical disorders are mainly associated with increased peripartal liver lipid concentrations. No relationship exists between conception success on the one hand and the concentrations of FFA and liver lipids 1 and 2 weeks p. p. on the other. In later infertile cows the parameters ketone bodies, liver glycogen and GGT are heaped outside the periparturient x ˉ ± s-range. The fertility and milk production indirectly or directly correlate secured to the body mass loss p. p. The individual differences between cows are significant.

11. For indirect determination of lipid concentration in the liver is the floating test suitable. For the relationship between relative density (y) and the lipid concentration (x) is the relationship y = 1.095 to 0.002 and x = x 500 (1.095 y). The liver floating test is recommended for use in veterinary practice. When interpreting the lipid concentration dependence is taken into state by lactation. Peripartal is a secure relationship (p ≤ 0.001) between energy deficit and concentration of liver lipids.

12. The chemically identifiable fat content of the liver correlated with an exponential function (p ≤ 0.001) with histologicalfat at 4 and 7 classes, however, lie with histological low and moderate fat deposits usually chemically no unphysiological lipid concentrations. The diagnostic value of the total lipid concentration in the liver depends on its origin and is limited.

13. A fatty liver diagnosis can be concluded with high certainly, when the concentration of FFA, bilirubin, and ketone bodies in blood resp. the triglyceride FFA ratio is increased. The BHB compared to the total ketone bodies deserve the privilege because it correlates closely with the liver lipid content. Abnormal liver lipid concentrations are often but not always associated with elevated AST activities.

14. The interpretation of the parameters FFA, bilirubin, ketone bodies, AST and liver lipids influences through the stage of lactation, when the FFA also loaded by stress as well as FFA and BHB to be considered by the feeding. Stress and feed-related changes but reach not the extent as in the case of clinical ketosis.

15. A clinical-chemical differentiation of reactive inflammatory and degenerative changes in the liver is possible with the parameters AST, GGT and total lipids. The ALT illustrates the severity of liver damage.

16. Triglycerides and total lipids reflect different feeding intensity peripartal scarely. Although the FFA triglyceride ratio correlated closely with liver fat, diagnosis justifies the effort but not determining. Blood glucose and liver glycogen correlate negative with the liver fat. Total protein, urea, creatinine, albumin and cholesterol can be seen only in individual cases or only in severe liver alterations pointed concentration variations.

17. The diagnosis of liver damages are recommended taking into account practical aspects:
- for the veterinarian in practice: the liver floating sample
- for laboratories and similar institutions:
First Level - bilirubin and ketone bodies (possibly differentiated)
Second Level - in addition FFA, GLDH, GGT, AST (ALT)
Third Level - histological examinations of liver biopsy, liver lipids, liver glycogen, optionally under clinical conditions liver function tests (Bromsulphthalein, Indocyanine green).

18. The antiketogenic effect of nicotinic acid in food deprivation as well as in the peripartal period shows favorable effects on carbohydrate metabolism, lowers bilirubin levels, but restricts the peripartal lipolysis not sufficient. Nicotine amide has peripartal the same effects. The use of nicotinic acid is especially recommended for pro- and metaphylaxis of ketosis. Their limited effect on lipolysis but strongly emphasizes that the prevention of increased lipolysis with fatty liver all the attention is devoted to.

19. Dehydrocholic acid (Billiton ®) affects the metabolism of dairy cows postpartal positive by reducing bilirubin, FFA and BHB concentrations and AST activities. The same therapeutic effects can be achieved in the treatment of cows with ketosis and indigestion. Billiton ® can be recommended in addition to the liver protective therapy for the treatment of liver diseases. The elimination of the primary disorder is required for successful treatment of secondary metabolic changes.
20. Phenylbutazone® as prostaglandin synthesis inhibitor affects the fat metabolism. In the first week p.p. has appliquéd phenylbutazone®in high doses on the metabolism, fertility and milk performances negative impacts. Its use should not be uncritically in stressful situations.

21. In the literaturecan be seen possible negativeeffectsof ACTHandglucocorticoidson lipidmetabolism andliverfunction. Changes inFFAconcentrations inbloodplasmacouldbeobservedexperimentallybutnotafter a singleapplication ofACTH andPrednisolutin sheep as well asduringa five-dayprednisolone applicationin cattle. Alsocarried outhistologicalexaminations providedno changes in cattleliverbiopsies.

22. Compared withprednisolone® (100and 300 mg/ cow)increasesa uniqueACTHapplication (300 IU / cow), the glucose concentration in bloodplasmastronger,until 3daysafter applicationremainsthe glucoseconcentration afterPrednisolonebutat a higher level. The sameappliestothetotalprotein. Because of thislonger duration oftheprednisolone® istherapeuticallypreferenceto give, for example in the treatmentof ketosis.

23. From the studiesoverallisa frequentoccurrence oflipiddepositsin the liverof different origins. Theirdiagnosisis certainor substantiallycertainaboutpossibleliver biopsyon theconcentrationofFFA, bilirubin andthe BHBin the bloodplasma.Theimportance oflipid depositionin thewhole organismand the roleof hormonaldysfunctionin the developmentofliver injuryrequire furtherinvestigations. Alsofor the treatmentofliverdamagearenew studies required.