《兽医临床病理英ppt课件教学教程》由会员分享，可在线阅读，更多相关《兽医临床病理英ppt课件教学教程（117页珍藏版）》请在金锄头文库上搜索。
1、Veterinary Clinical Pathology兽医临床病理学College of Veterinary Medicine, South China Agricultural University, Guangzhou, China , 510642PrefaceVeterinary Clinical Pathology:Veterinary Laboratory MedicineInclude:1 Clinical Hematology2 Clinical biochemistry3 Clinical cytology4 Clinical microbiology5 Clinica
2、l parasitology6 Clinical toxicologyPrefaceGeneral Laboratory concepts Veterinarians have many choices regarding laboratory testing. Important factors include:-Need and usefulness-Practicality-Cost-effectiveness-Accuracy-Turnaround timeComplete Blood Count and Bone Marrow Examination:general comments
3、 and selected techniquesComplete blood countQuantitation techniquesBlood smear analysisOther determinationsBone marrow examinationBone marrow biopsy and aspirateComplete blood count (CBC)CBC is a profile of tests used to describe the quantity and quality of the cellular elements in blood and a few s
4、ubstances in plasma.CBC is a cost-effective screen the detects many abnormalities and disease conditions.Bone marrow examination is used in selected instances to answer questions the more readily available CBC cannot.Quantitation TechniquesSample submissionMicrohemotcritHemoglobin concentrationCell
5、countsAbsolute nucleated RBC countAutomated hematology cell countersBlood Smear AnalysisMaking the smearStainsEvaluating blood smears -platelet morphology -leukocyte morphology -leukocyte estimation -leukocyte differential count -erythrocyte morphologyBone Marrow ExaminationBone marrow is usually ex
6、amined to answer certain question that arose from evaluating the CBC.Indications for bone marrow examination include: -nonregenerative anemia -Persistent neutropenia -Persistent thrombocytopenia -Unexplained polycythemia or thrombocytosis -Atypical cells in bloodErythrocytesBasic concepts of erythro
7、cyte function,metabolism, production and breakdownHeme synthesisGlobin synthesisIron metabolismErythrocyte metabolismEmbden-meyerhof pathway -Glycolysis generates ATP and NADHPentose phosphate pathway -This pathway produces NADPHMethemoblobin reductase pathway -Methemoglobin(Fe3+) cannot transport o
8、xygenRapoport-luebering pathway -2,3 diphosphoglycerate(2,3 DPG)Red blood cells The fundamental stimulus for production of red blood cells (erythropoiesis) is erythropoietin(红红细细胞胞生生成成素素）, a glycoprotein produced by the kidneys in response to renal tissue hypoxia. Other hormones, such as corticoster
9、oids, thyroid hormone and androgens, stimulate the production or release of erythropoietin but have no intrinsic erythropoietic activity.The average lifespan of a circulating erythrocyte is 110-120 days in the dog and 68 days in the cat. Aged or damaged red cells are removed primarily by macrophages
10、 in the liver, spleen and bone marrow. NeutrophilsThe production of neutrophils, eosinophils and basophils is termed granulopoiesis. The neutrophils in the bloodstream either circulate freely (the circulating pool) or adhere to the vascular endothelium (the marginal pool). In the dog the marginal po
11、ol and the circulating pool are approximately equal in size, whilst in the cat the marginal pool is two to three times larger than the circulating pool. There is a continual exchange of cells between these two pools. The half-life of circulating neutrophils is only 6-14 hours, after which time they
12、leave the circulation and pass into the tissue pool. The circulating time is shortened during acute infections as neutrophils pass to the site of infection in the tissues. The main function of the neutrophil is the phagocytosis of pyogenic bacteria. Lymphocytes Lymphoid primitive stem cells divide a
13、nd differentiate into pre-B lymphocytes and pre-T lymphocytes in the bone marrow. Pre-T lymphocytes mature and proliferate into T cells in the thymus. Pre-B cells proliferate in the bone marrow and migrate to peripheral lymphoid organs (spleen and lymph nodes) where further proliferation takes place
14、. Platelets Platelets are produced from the cytoplasm of megakaryocytes Once in the circulation, platelets survive for 8-12 days. Up to 20-30% of circulating platelets can be sequestered in the spleen; the figure may be a high as 90% if there is splenomegaly. Old or damaged platelets are removed fro
15、m the circulation by the spleen, liver and bone marrow. ROUTINE HAEMATOLOGYThe complete blood count is an integral part of the diagnostic investigation of any systemic disease process. It consists of two components: A quantitative examination of the cells, including : packed cell volume (PCV) total
16、red cell count (RBC) total white cell count(WBC) differential white cell count platelet count mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total plasma protein concentration.A qualitative examination of blood smears for changes
17、 in cellular morphology. Table 1 Reference values for red cell indices DogsCatsTotal red blood cells(x1012/L)5.58.55.010.0Haemoglobin(g/dl)12.018.08.015.0PCV (L/L)0.370.550.260.45MCV (fl)60.077.039.055.0MCH (pg)19.524.512.517.5MCHC (g/dl)32.037.030.036.0ROUTINE HAEMATOLOGYRED BLOOD CELL INDICESMCV(f
18、l飞升飞升)= PCV (L/L) 1000/ total red cells ( 1012/L) MCH (pg皮克皮克) = total haemoglobin (g/dl) 10/ total red blood cells ( 1012/L) MCHC (g/dl) = total haemoglobin (g/dl)/PCV (L/L) RBC indices are helpful in the classification of certain anemias.ROUTINE HAEMATOLOGYDifferential white cell countsThe differe
19、ntial white cell count is performed by counting 200 leucocytes in a blood smear. The cells are counted along the long edge of the smear, using the battlement meander method: four high-power fields are counted in one direction, then four more in a direction at right angles to the first, and so on, fo
20、llowing the shape of a battlement. The percentage of each type of cell is determined. This percentage is then multiplied by the total white cell count to obtain an absolute count for each cell type. ROUTINE HAEMATOLOGYPlasma protein concentration(Reference range: 60-80 g/1 for the dog and cat) Total
21、 plasma protein (TPP) and PCV should be interpreted together. Qualitative examination of a blood smearA blood smear should always be evaluated when automated cell counts are made or when in-practice instrumentation is limited to a centrifuge for PCV Preparation of a blood smear A small drop of blood
22、 is placed on one end of a glass slide, using a capillary tube. A spreader slide (made by breaking off the comer of another slide, after scoring it with a glass cutter or diamond writer) is placed on to the slide holding the blood drop, in front of the drop and at an angle of 20-40. ROUTINE HAEMATOL
23、OGYANAEMIAANAEMIAAnaemia is characterized by an absolute decrease in red cell count, haemoglobin concentration and PCV. Acute haemorrhageAcute haemorrhage Acute haemorrhage may be due to trauma or surgery, bleeding gastrointestinal ulcers or tumours, rupture of a vascular tumour (e.g. splenic haeman
24、giosarcoma), or a coagulopathy (e.g. warfarin toxicity). Immediately following acute haemorrhage the red cell parameters, including PCV, are normal because both red cells and plasma have been lost in proportion. Compensatory mechanisms such as splenic contraction may further offset any fall in PCV.
25、The PCV falls when blood volume is replaced by interstitial fluid and so does not indicate the full magnitude of blood loss for at least 24 hours after the onset of haemorrhage. ROUTINE HAEMATOLOGY Chronic haemorrhageChronic external blood loss (e.g. chronic gastrointestinal haemorrhage, renal or bl
26、adder neoplasia) initially results in a regenerative anaemia but gradually the anaemia becomes non-regenerative as the iron stores become depleted. Young animals become iron-deficient more bone marrow is already very active producing red cells quickly than adults following blood loss, partly because
27、 they have low iron stores and partly because their to match their growth rate and so has less capacity to increase its rate of haemopoiesis. Haemolytic anaemiasMost cases of haemolytic anaemia are immune-mediated. In the dog most cases of immune-mediated is haemolytic anaemia (IHA) are primary (idi
28、opathic) and are termed autoimmune haemolytic anaemia (AIHA). IHA may occur in association with: drugs(e.g. potentiated sulphonamides); lymphoreticular diseases (e.g. lymphoid leukaemia); systemic lupus erythematosus; or infections (e.g. Babesia, bacterial endocarditis). ROUTINE HAEMATOLOGYDISORDERS
29、 OF WHITE CELL NUMBERNeutrophiliaFigure 3.20 Causes of neutrophilia Physiological response (fear, excitement, exercise) Stress/corticosteroid-induced Acute inflammatory response: bacterial infection (localized or generalized), immune-mediated disease, necrosis,e.g.pancreatitis, neoplasia, especially
30、 with tumor necrosis. Chronic granulocytic leukaemia Neutrophil dysfunction Paraneoplastic syndromes Neutropenia The three main causes of neutropenia are: An overwhelming demand for neutrophils Reduced production of neutrophils in the bone marrow Defective neutrophil maturation in the bone marrow. A
31、n overwhelming demand for neutrophils may occur with peracute bacterial infections, especially Gram-negative sepsis and endotoxaemia. Other possible causes include peritonitis, pyometra（子宫蓄脓）（子宫蓄脓）, aspiration pneumonia and canine parvovirus infection. DISORDERS OF WHITE CELL NUMBEREosinophilia Eosi
32、nophilia Eosinophils are distributed in the body among various pools in a similar way to neutrophils, although the bone marrow storage pool is minimal. Eosinophils circulate in the bloodstream for only a few hours before entering the tissues, where they may live for several days. Their two main func
33、tions are to kill parasites and to regulate allergic and inflammatory reactions. Eosinopenia Eosinopenia Eosinopenia in combination with lymphopenia occurs following stress, administration of corticosteroids and in spontaneous hyperadrenocorticism (Cushings syndrome). Basophilia Basophilia Basophils
34、 contain inflammatory mediators such as histamine and heparin and function in a similar manner to mast cells in hypersensitivity reactions. DISORDERS OF WHITE CELL NUMBERLymphocytosis Lymphocytosis Causes of lymphocytosis 1. Physiological lymphocytosis, with concomitant neutrophilia, in response to
35、excitement (especially cats) 2. Strong immune stimulation (e.g. in chronic infection, viraemia or immune-mediated disease) 3. Chronic lymphocytic leukaemia 4. Hypoadrenocortiscism (lymphocytosis may be associated with an eosinophilia) 5. Increased numbers of large reactive lymphocytes may occur tran
36、siently following vaccination 6. Young animals have a higher lymphocyte count than adult animalsDISORDERS OF WHITE CELL NUMBERLymphopeniaLymphopeniaCauses of lymphopenia are listed.Causes of lymphopenia are listed.StressGlucocorticoid therapyHyperadrenocorticismChylothorax (loss of lymphocytes into
37、the pleural space)Lymphangiectasia (loss of lymphocytes into the gut)Acute phase of most viral infections (e.g. canine distemper, parvovirus, FeLV)Septicaemia/endotoxaemiaDISORDERS OF WHITE CELL NUMBERDogsCats percentageAbsolute valuepercentageAbsolute value(10/Total WBCN/a617N/a5.519.5Band neutropi
38、ls0300.30300.3Neutropils6077311.535372.512.5Lymphocytes123014.820551.57Monocytes3100.21.51401.5Eosinopils2100.11.321201.5basopilsrarerarerareRareReference ranges for total and differential white blood cell countsTable 2 shows the alterations in some of parameters in various diseases.Laboratory asses
39、smentTests to assess primary haemostasis include: Platelet count Bleeding time Clot retraction.Tests to assess secondary haemostasis include: Whole blood clotting time (WBCT) Activated clotting time (ACT) Activated partial thromboplastin time (APPT) One-stage prothrombin time (OSPT) Thrombin time (T
40、T)DISORDERS OF WHITE CELL NUMBERDisseminated intravascular coagulation (DIC): This may be triggered by a wide variety of diseases, including endotoxaemia neoplasia (especially haemangiosarcoma 血管肉瘤血管肉瘤) acute infections (e.g. infectious canine hepatitis) haemolytic anaemia pancreatitis heat stroke.
41、The clinicopathological features of DIC are: Thrombocytopenia Increased OSPT/APTT Elevated FDPs Low fibrinogen Schistocytes in the blood film. DISORDERS OF WHITE CELL NUMBER兽医临床病理学兽医临床病理学College of Veterinary Medicine, SCAU, Guangzhou,China 510642Clinical biochemistryIntroduction Serum proteins Tota
42、l protein and albumin Globulins Indicators of renal function Urea nitrogen Creatinine Markers of hepatic disease Alanine aminotransferase Aspartate aminotransferase Alkaline phosphatase Gamma-glutamyi transferase Bilirubin Bile acids Ammonia Pancreatic disease Amylase LipaseElectrolytes Sodium; Pota
43、ssium; Chloride Magnesium; Calcium; Phosphorus Muscle enzymes Creatine kinaseAspartate aminotransferase Carbohydrate metabolism GlucoseFructosamine Lipid metabolism CholesterolTriglycerides Miscellaneous tests Iron Lead ZincCopper Chemical profiles and test selection SERUM PROTEINSTotal protein and
44、albuminTotal protein and albumin Physiology The circulating proteins are synthesized predominantly in the liver, although plasma cells also contribute to their production. Quantitatively the single most important protein is albumin (35-50% of the total serum protein concentration). The other protein
45、s are collectively known as globulins. The functions of proteins are many and varied but include maintenance of plasma osmotic pressure, transport of substances around the body (e.g. ferritin铁铁蛋蛋白白, ceruloplasmin血血浆浆铜蓝蛋白铜蓝蛋白), humoral immunity, buffering and enzyme regulation. Indications for assay
46、The measurement of proteins is generally included in an initial health screen in all patients but especially where intestinal, renal or hepatic disease or haemorrhage is suspected. Analysis Protein concentrations can be estimated in serum, plasma, urine or body fluids with a refractometer or by spec
47、trophotometry. Serum albumin levels are measured by bromocresol green dye溴溴甲甲酚酚绿绿 binding and the serum globulin is calculated by subtraction of the albumin concentration from the total protein concentration. Reference ranges Neonates and very young animals have lower concentrations of albumin and g
48、lobulins (due to minimal quantities of immunoglobulins). As the animal gains immunocompetence the protein concentrations rise to reach adult values. Physiological decreases in albumin may be noted during pregnancy. Critical values Marked hypoalbuminaemia ( 1.030 in dogs, 1.035 in cats) supports the
49、diagnosis of a prerenal azotaemia. INDICATORS OF RENAL FUNCTIONCreatinineCreatininePhysiology Creatinine is formed from creatine in the muscles in an irreversible reaction. The quantity of creatinine produced depends upon diet (small contribution) and the muscle mass. Disease affecting the muscle ma
50、ss may affect the daily creatinine production. Both urea and creatinine are freely filtered at the renal glomerulus but urea is subject to tubular reabsorption and thus creatinine is said to be a better indicator of GFR.Analysis Creatinine can be measured in serum, plasma or abdominal fluid by spect
51、rophotometric methods. Reference ranges Dogs 20-110 umol/L Cats 40-150umol/L INDICATORS OF RENAL FUNCTIONCauses of low serum creatinine Causes of low serum creatinine Since the daily production of creatinine is dependent upon the muscle mass of the animal, the body condition should be considered whe
52、n interpreting serum creatinine concentrations. A poor body condition may be associated with low concentrations while minor rises in such cases may be more significant than in other individuals. Causes of increased serum creatinine Decreased glomerular filtration is the major cause of raised serum c
53、reatinine. However, approximately 75% of nephron function must be impaired before serum creatinine (and urea) is increased. Creatinine is considered a more reliable indicator of GFR than is urea nitrogen, since there are fewer factors which influence the serum concentration of creatinine. INDICATORS
54、 OF RENAL FUNCTIONThe biochemical parameters used to assess liver pathology may be divided into two classes: the hepatic enzymes that reflect liver damage and cholestasis, and the endogenous indicators of liver function. Alanine aminotransferase (ALT) is the most useful enzyme for identifying hepato
55、cellular damage in dogs and cats but should not be used alone as a screening test for liver disease. The production of other enzymes, i.e. alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), is increased secondary to intra- and extrahepatic cholestasis. These enzymes are markers of chol
56、estatic disease. Bilirubin, serum albumin and serum bile acids are considered to be indicators of hepatic function . It is common for extrahepatic disease (e.g. pancreatitis, diabetes mellitus, hyperadrenocorticism and inflammatory bowel disease) to cause abnormalities of these biochemical parameter
57、s. MARKERS OF HEPATIC DISEASE Alanine aminotransferase (ALT) Alanine aminotransferase (ALT) PhysiologyPhysiology ALT is found in the cytosol of hepatocytes and in muscle tissue in the dog and cat. Activities in the serum are elevated by leakage of the enzyme secondary to an increase in hepatocyte me
58、mbrane permeability or cell necrosis. The former may simply be a consequence of hypoxia and need not reflect cell death. Increased serum ALT may be noted within 12 hours of an acute hepatic insult but can take 3-4 days to reach peak levels after experimental cholestasis（胆胆汁汁阻阻塞塞）. The degree of incr
59、ease in enzyme activity correlates approximately with the number of hepatocytes affected but does not indicate the nature, severity or reversibility of the pathological process. ALT activity is not an indicator of hepatic function. Indications for assay Serum ALT is a useful aid in the diagnosis of
60、hepatic disease and is measured where the clinical signs might suggest a hepatopathy, e.g. weight loss, anorexia, polydipsia, vomiting, diarrhoea, ascites and jaundice. Analysis The activity of the enzyme (in international units) is measured in serum or plasma by spectrophotometric methods under spe
61、cified conditions.Reference rangesDogs 100 units/L Cats 75 units/LMARKERS OF HEPATIC DISEASE Causes of raised ALT activityCauses of raised ALT activity Guidelines for the interpretation of raised liver enzyme activities in relation to liver diseases are given in Chapter liver. The majority of diseas
62、es that affect the liver could potentially cause an increase in serum ALT activity but those pathological processes that might cause a marked increase include parenchymal disease/ damage, cholangitis, cholangiohepatitis, chronic hepatitis, anoxia, cirrhosis and diffuse neoplasia, e.g. lymphoma (lymp
63、hosarcoma). However, in some cases these diseases may be accompanied by a negligible increase or no increase in serum ALT activity. Causes of reduced ALT activityCauses of reduced ALT activity An artefactual reduction in serum enzyme activities may result from substrate depletion. Dilution and repea
64、t assay of the sample are necessary to exclude this phenomenon. Reduced ALT activities (below the reference range) are generally not considered to be of clinical significance, but the possibility of chronic liver disease and nutritional deficiencies (zinc or vitamin B6 ) should be considered. MARKER
65、S OF HEPATIC DISEASE Aspartate aminotransferase (AST) (see also Muscle enzymes) Physiology AST is located in the mitochondria of the cell and is present in significant quantities in hepatocytes, erythrocytes and in muscle. AST is therefore not liver-specific but, like ALT, its activity in the serum
66、is elevated by leakage of the enzyme from the cell. Indications for assay AST is included in diagnostic profiles for investigation of suspected liver disease or muscle disease.AnalysisThe enzyme activity is measured in serum and heparinized plasma by spectrophotometry. Reference ranges Dogs 7-50 uni
67、ts/L Cats 7-60 units/LCauses of raised ASTThe most common causes of increased AST are hepatic disease, muscle disease (trauma, inflammation) and haemolysis. Concurrent measurement of other hepatic enzymes (ALT, ALP, GGT) and hepatic function indicators (albumin, urea, bilirubin, bile acids) are esse
68、ntial to establish the origin of the increased serum AST and to provide further information regarding liver damage and function (see Chapter 9). With respect to liver damage, the serum activity of AST tends to parallel that of ALT. MARKERS OF HEPATIC DISEASE Alkaline phosphatase (ALP, SAP)Alkaline p
69、hosphatase (ALP, SAP)PhysiologyIn dogs and cats there are isoforms of ALP located in brush borders in the liver, placenta, intestine, kidney and bone. In the dog there is also a steroid-induced isoenzyme (SIALP), the origin of which has not been fully determined. The production of SIALP is increased
70、 by the administration of glucocorticoids (oral, parenteral or topical), by excessive production of endogenous glucocorticoids (hyperadrenocorticism) and in association with chronic disease (e.g. renal or hepatic). The liver isoenzyme is responsible for the serum activity in the normal adult dog and
71、 cat. Indications for assay Serum ALP is one of the tests commonly included in screening profiles for hepatic disease (cholestasis) and hyperadrenocorticism. It is therefore useful where the clinical signs suggest either of these diagnoses, e.g. weight loss, anorexia, polydipsia, vomiting, diarrhoea
72、, ascites and jaundice.AnalysisSerum ALP activity is measured in serum or heparinized plasma by spectrophotometry. Reference ranges Dogs 200 units/L Cats 30 umol/L, for example in hyperadrenocorticism.The use of the bile acid stimulation test may improve the sensitivity of testing. For this, serum b
73、ile acid concentrations are measured in a sample collected after a 12-hour fast (fasting bile acid concentration) and 2 hours after a fatty meal (postprandial（餐后）（餐后） bile acid concentration). In one study of 108 cats, the postprandial bile acid concentration was found to have the highest sensitivit
74、y of any single test for the diagnosis of feline liver disease. MARKERS OF HEPATIC DISEASE Ammonia Ammonia Physiology Dietary proteins are hydrolysed in the gut to amino acids which, in turn, may be degraded by intestinal bacteria, producing ammonia. Ammonia is transported to the liver where it is u
75、sed as a precursor in the synthesis of urea. Increased blood ammonia concentrations are observed in some patients with diffuse liver disease (with a reduced capacity for urea synthesis) and in individuals with portosystemic shunts. Indications for assay Ammonia is used in the evaluation of hepatic f
76、unction; the indications for measurement are the same as for bile acids.AnalysisAmmonia is measured in blood, serum or plasma by dry reagent and enzymatic methods. Samples should be collected into a chilled sample tube and stored on ice until analysis, which must be carried out within 20 minutes of
77、collection.Reference ranges Dogs 0-60 umol/L Cats 0-60 umol/L MARKERS OF HEPATIC DISEASE Causes of increased ammoniaIncreased ammonia concentrations are associated with feeding high-protein diets and with intestinal haemorrhage (due to the increased delivery of amino acids to the intestinal bacteria
78、). Diffuse hepatic disease, resulting in the failure of conversion of ammonia to urea, and portosystemic shunts (congenital and acquired) will also produce increased serum ammonia concentrations. MARKERS OF HEPATIC DISEASE PANCREATIC DISEASEAmylase Amylase Physiology Amylase（淀淀粉粉酶酶） is a calcium-dep
79、endent enzyme, produced by the pancreatic acinar cells, which hydrolyses complex carbohydrates. The enzyme passes directly from the pancreas into the circulation where it is filtered by the renal tubules; the inactivated enzyme is reabsorbed by the tubular epithelium. Amylase activity in the tissues
80、 of the dog and cat is highest in the pancreas but is also found in the intestines and liver. Indications for assay Amylase should be measured when the presenting signs might suggest pancreatitis（胰胰腺腺炎炎）, e.g. vomiting, abdominal pain or icterus, or when there is free peritoneal fluid. Analysis Amyl
81、ase activities may be measured in serum, heparinized plasma and abdominal fluid using spectrophotometric methods. Reference rangesDogs 400-2000 units/L Cats 400-2000 units/L Causes of increased amylase The tissue distribution of amylase is not restricted to the pancreas and therefore raised serum ac
82、tivities are not specific for pancreatitis. Reduced glomerular filtration (prerenal, renal, postrenal) is often associated with an increased serum amylase activity but this is commonly less than two to three times greater than the upper limit of the reference range. Serum activities above this level
83、 are suggestive of pancreatitis but the degree of increase does not correlate well with the severity of pancreatitis. If an azotaemic（氮氮血血症症） patient has an amylase activity two to three times the upper limit of the reference range then pancreatic disease must be considered. The simultaneous measure
84、ment of amylase and lipase in cases of suspected pancreatitis is advisable while additional tests of renal and hepatic function should also be included in the biochemical profile. Amylase is not a reliable indicator of pancreatitis in cats . In cases that present with free peritoneal fluid, full ana
85、lysis of the fluid (protein concentration, cell counts and cytological examination) and measurement of the serum and fluid amylase activities may be useful. The presence of a non-septic exudate with greater amylase activity than the serum may be associated with pancreatitis or bowel rupture. PANCREA
86、TIC DISEASELipase Lipase PhysiologyPhysiologyLipase is a digestive enzyme, produced by the pancreatic acinar cells, that hydrolyses triglycerides. The enzyme is cleared from the circulation by renal inactivation. As with amylase, lipase may originate from pancreatic or extrapancreatic sources. Pancr
87、eatic damage and inflammation results in the release of lipase into the surrounding gland and peritoneal tissue which may cause the development of necrosis in the peripancreatic peritoneal fat. Indications for assay Indications for the measurement of lipase are the same as for amylase. Amylase and l
88、ipase assays should be performed simultaneously in cases in which pancreatitis is suspected, but the increases in enzyme activities are often not parallel (marked increases in one enzyme may be associated with minimal increases in the other). Analysis Lipase activities are measured in serum, heparin
89、ized plasma and body fluids using turbidimetric methods. Reference ranges Dogs 0-500 units/L Cats 0-700 units/L PANCREATIC DISEASECauses of raised serum lipase Since lipase originates from both pancreatic and extrapancreatic tissue, an increase in serum activity is not diagnostic of pancreatitis. In
90、creased serum activity is also noted in azotaemic patients, although the values generally do not exceed two to three times the upper limit of the reference range. In addition, moderate elevations of lipase (up to 5-fold increases) have been reported in association with administration of dexamethason
91、e without evidence of histological changes in the pancreas. A normal lipase activity does not preclude pancreatic disease.Lipase has been reported to be persistently elevated in cats with experimentally induced pancreatitis but this is not a consistent finding in naturally occurring disease. PANCREA
92、TIC DISEASECARBOHYDRATE METABOLISMPhysiology Glucose is the principal source of energy for mammalian tissues and is derived from the diet and hepatic gluconeogenesis. The blood concentration is controlled by hormones which regulate its entry into, and removal from, the circulation (insulin, glucagon
93、, adrenaline, cortisol). In the kidney of the dog and cat, glucose entering the glomerular ultrafiltrate is reabsorbed by the renal tubules. However, the renal reabsorption of glucose is overwhelmed in the presence of blood glucose concentrations greater than 10-12 mmol/1, resulting in glucosuria. I
94、ndications for assay Measurement of blood glucose is essential where presenting clinical signs could suggest ： diabetes mellitus (polydipsia, polyuria, weight loss, cataract formation), diabetic ketoacidosis (vomiting, diarrhoea, anorexia) hypoglycaemia (weakness, collapse, seizures, disorientation,
95、 depression, blindness). In addition, the assay is included in general health screens where it may provide supportive evidence for other disease processes (hyperadrenocorticism, hepatic disease). Measurement of the blood glucose concentration is the ideal method of monitoring the stabilization of di
96、abetic patients on insulin therapy and allows optimization of the therapeutic regimen. In such cases, glucose is measured in samples collected at 2-hourly intervals, allowing calculation of the duration of action and peak time of action of the administered insulin. GlucoseAnalysis Reagent strips: Ra
97、pid-analysis reagent strips require the use of whole blood with no anticoagulant. Laboratory analysis: Spectrophotometric methods (enzymatic or chemical) arc generally used for the measurement of blood glucose. Where in-house equipment demands the use of heparinized plasma, the sample must be separa
98、ted immediately after collection. This prevents depletion of the plasma glucose by the erythrocytes. Collection of the blood into fluoride oxalate is the preferred method of preventing erythrocyte glucose utilization when a delay in analysis is anticipated, such as during transport to a commercial l
99、aboratory. Reference ranges Dogs 3.5-5.5 mmol/L Cats 3.5-6.5 mmol/L GlucoseCauses of hypoglycaemia Marked hypoglycaemia (glucose 2 mmol/L) most commonly results from overproduction of insulin or excessive utilization of glucose by neoplastic cells. Insulin-secreting tumours of the pancreas (insulino
100、mas) produce biologically active hormone which increases the uptake of glucose by the body tissues and impairs hepatic gluconeogenesis, resulting in hypoglycaemia. In one study of dogs with insulinomas the mean (+SD) plasma glucose concentration was 2.14(0.82) mmol/1. Extrapancrcatic tumours occasio
101、nally cause hypoglycaemia by secretion of an insulin-like substance or by increased utilization of plasma glucose. GlucoseNeoplastic: Insulin-secreting tumour of the pancreas (insulinoma) Hepatocellular carcinomaEndocrine: Hypoadrenocorticism Hepatic insufficiency: Congenital vascular shunts Acquire
102、d vascular shunts Chronic hepatic fibrosis (cirrhosis) Hepatic necrosis (e.g. hepatotoxins, bacterial infection, trauma)GlucoseFigure 4.19: Causes of hypoglycaemia in the dog. Cats may rarely be affected by insulinoma.Substrate deficiency: Neonatal hypoglycaemia Juvenile hypoglycaemia Hunting dog hy
103、poglycaemia Glycogen storage diseaseSepsisCauses of hyperglycaemiaHyperglycaemia commonly results from a relative or absolute lack of insulin. This leads to impaired tissue utilization of plasma glucose and an increase in the rate of gluconeogenesis. Mild hyperglycaemia (6.7-10 mmol/L) in the dog ma
104、y be noted as part of an adrenaline stress response or secondary to excessive secretion or administration of other diabetogenic hormones, in particular glucocorticoids and progesterone. The mild hyperglycaemia is a result of the hormonal antagonism of the actions of insulin. In addition, mild hyperg
105、lycaemia may be noted in the postprandial period in dogs fed a sugar-rich diet such as semi-moist foods. A persistent, moderate to marked hyperglycaemia in the dog is consistent with diabetes mellitus. Such cases do not present with clinical signs (polyuria and polydipsia) until the renal threshold
106、for glucose is exceeded, resulting in osmotic diuresis. In the cat, an adrenaline-induced stress response may produce a moderate or marked increase in glucose concentration. The diagnosis of diabetes mellitus is often difficult in cats and confirmation requires documentation of persistent hyperglyca
107、emia with compatible clinical signs.Glucose Figure 4.20: Causes of hyperglycaemia. Adrenaline stress response (especially marked in cats) Postprandial Diabetes mellitus Hyperadrenocorticism (dogs and rarely cats) Acromegaly (cats) Acute pancreatitis (dogs and cats)Renal insufficiency GlucoseFructosa
108、minePhysiology Fructosamine is a glycated serum protein which is formed by the non-enzymatic reaction between a sugar and an amino acid. The total amount of fructosamine formed is proportional to the serum glucose concentration during the lifespan of the proteins. In dogs and cats, fructosamine has
109、been found to be a useful parameter in the diagnosis and management of diabetes mellitus.Indications for assay Serum fructosamine concentrations are useful in the diagnosis of diabetes mellitus and in identifying persistent hyperglycaemia during therapy. Measurement of fructosamine may also be helpf
110、ul in confirming the presence of persistent hypoglycaemia. Analysis Fructosamine is measured using a method based on the reducing ability of fructosamine in alkaline solution. Reference ranges Dogs 250-350 umol/LCats 150-270 umol/LCauses of low serum fructosamine A low serum fructosamine concentrati
111、on has been recorded in a dog with an insulin-secreting tumour of the pancreas (insulinoma). It has been suggested that the measurement of serum fructosamine in addition to glucose and insulin may be helpful in confirming the presence of insulinomas. Causes of raised fructosamine Raised serum concen
112、trations of fructosamine reflect persistent hyperglycaemia over the preceding 2-3 weeks. In dogs with diabetes the serum fructosamine concentration is significantly greater than in dogs with other diseases. Fructosamine is also useful for confirming diabetes mellitus in the cat and can be helpful in
113、 identifying persistent hyperglycaemia after initial stabilization on insulin therapy. FructosamineLIPID METABOLISMPhysiology Cholesterol is the most common steroid in the body tissues and acts as a precursor compound for steroid hormone and bile salt synthesis. The majority of the bodys cholesterol
114、 is synthesized by the liver, but the remainder originates from dietary sources. Excess cholesterol is excreted in the bile. Indications for assay Hypercholesterolaemia is often associated with endocrine disease in the dog and cat and is frequently measured as part of a general health profile in the
115、se species. Raised plasma cholesterol alone is not commonly responsible for the development of clinical disease in the dog and cat. However, marked hypercholesterolaemia and hypertriglyceridaemia secondary to thyroid dysfunction in dogs have been associated with the development of peripheral vascula
116、r disease. Analysis Cholesterol concentrations are assayed in serum, heparinized plasma or EDTA plasma using spectrophotometric, automated direct and enzymatic methods. Cholesterol Figure 4 Causes of alterations in plasma cholesterol concentrations. Hypocholesterolaemia Protein-losing enteropathy Ma
117、ldigestion/malabsorption Hepatopathy (portocaval shunt, cirrhosis) Hypercholesterolaemia Postprandial hyperlipidaemia Secondary hyperlipidaemia: Hypothyroidism Diabetes mellitus Hyperadrenocorticism Cholestatic disease Nephrotic syndrome Causes of hypercholesterolaemia A marginal increase in the cho
118、lesterol concentration may be noted in samples collected in the postprandial period versus a fasted sample. This increased level generally does not exceed the reference range for the species. Hypercholesterolaemia in the dog and cat is most commonly associated with endocrine disease (diabetes mellit
119、us, hypothyroidism, hyperadrenocorticism). In each of these endocrine disorders there may be a concurrent increase in serum triglyceride concentration. Hypercholesterolaemia may also be noted in cholestatic disease and glomerulonephritis(肾小球性肾炎）肾小球性肾炎）.Further specialist investigation (e.g. lipoprot
120、ein electrophoresis) may be necessary if no underlying systemic or endocrine disease can be identified and the hypercholesterolaemia is marked and persistent. Triglycerides Physiology The triglycerides are the most abundant lipids in the body and their storage in adipose tissue provides an essential
121、 reserve of chemical energy for tissue requirements. They are derived from the diet and also synthesized de novo （重新）（重新）in the liver.Indications for assay Fasting hypertriglyceridaemia in the dog and cat is a pathological finding. The presence of large triglyceride-rich lipoproteins imparts a turbi
122、dity to the plasma or serum (lipaemia). Triglycerides should therefore be measured in all fasting blood samples that appear to be lipaemic. Clinical manifestations of hypertriglyceridaemia include： recurrent abdominal pain, alimentary signs, seizures. Causes of hypotriglyceridaemia Hypotriglyceridae
123、mia has not been consistently associated with any specific disease process although it has been reported in several cases of acute and chronic hepatic disease. Causes of hypertriglyceridaemiaThe most common cause of apparent hypertriglyceridaemia in the dog and cat is a failure to obtain a fasting s
124、ample (postprandial hyperlipidaemia). If hypertriglyceridaemia is documented in a sample collected after a 12-hour fast, endocrine and systemic disease should be excluded (diabetes mellitus, hypothyroidism, hyperadrencorticism, glomerulonephritis). Many dogs with spontaneous acute pancreatitis have
125、increased serum triglyceride concentrations. The relationship between pancreatitis and hyperlipidaemia has not been fully elucidated but it appears that the increased triglyceride concentration may predispose patients to pancreatic pathology. Figure 5 Causes of hypertriglyceridaemia in the dog and c
126、at Postprandial hyperlipidaemiaSecondary hyperlipidaemia: Hypothyroidism Diabetes mellitus Hyperadrenocorticism Acute pancreatitisPrimary hyperlipidaemia: Idiopathic hyperchylomicronaemia of the Miniature Schnauzer Familial hyperchylomicronaemia（乳糜微粒血症）（乳糜微粒血症） in the catIdiopathic hypertriglycerida
127、emia CHEMICAL PROFILES AND TEST SELECTION On the initial presentation of an ill patient, a clinician formulates a list of differential diagnoses based on the history and clinical findings. Where the clinical findings are specific, e.g. pallor of the mucous membranes suggestive of anaemia, then steps
128、 are taken to confirm this suspicion and to elucidate the possible cause. A wider, more comprehensive investigation is necessary when clinical signs may be caused by many metabolic disorders; for example, polydipsia in the dog could be the result of endocrine disease, renal disease or hepatic diseas
129、e. The selection of tests depends upon the differential diagnoses, the range of conditions that must be excluded, the availability of the tests, and the cost of tests. In the case of the polydipsic dog, a cost-effective profile is required to cover the possibility of organ failure (renal, hepatic),
130、endocrine disease (diabetes mellitus, hyperadrenocorticism) and hypercalcaemia.Some of these differentials may be excluded or confirmed on the basis of individual tests (e.g. urea and creatinine for renal disease) but inclusion in a more comprehensive profile allows the simultaneous assessment and c
131、ost-effective exclusion of many other causes of polydipsia. When the clinical signs are vague and a general health screen is required, then it is necessary to select a broad range of analytes which will reflect a number of common diseases or pathological states. The inclusion of tests that are not o
132、rgan-specific but which provide general information regarding the hydration and essential homeostatic mechanisms is worthwhile, e.g. total proteins, albumin, electrolytes, glucose.CHEMICAL PROFILES AND TEST SELECTIONProfileHealthPre-anaestheticscreen*Extended* health screenPolydipsia profile Seizure
133、 profileRenal profileHepatic profileTestsFBC, TP, albumin, globulin, ALT, ALP, GGT, bilirubin, amylase, urea, creatinine, glucose, urinalysisFBC， TP, albumin, globulin, ALT, ALP, bilirubin, urea, creatinine, glucoseAs health screen plus bile acids, electrolytes, cholesterol, CK, calcium, phosphorus
134、FBC, TP, albumin, globulin, ALT, ALP, bilirubin, bile acids, CK, cholesterol, urea, creatinine, glucose, calcium, phosphorus, electrolyte screen, urinalysis (SG, dipstick and sediment examination). FBC, TP, albumin, globulin, ALT, ALP, bile acids, urea, creatinine, glucose, calcium, CK, phosphorus,
135、magnesium, electrolyte screenPCV, TP, albumin, globulin, urea, creatinine, sodium, potassium, calcium, phosphorus, urinalysis (SG dipstick and sediment examination)TP, albumin, globulin, ALT, ALP, AST, GGT, bilirubin, bile acids, cholesterolIndicationsRoutine screeningScreen for existing disease pri
136、or to routine surgeryGastrointestinai.endocrine disease and nonlocalizing signsPolydipsiaSeizures, weakness, episodic collapseMonitoring hepatotoxicityGastrointestinal SystemFecal analysisExamination of vomitusBlood testsImaging techniquesEndoscopyDysphagia and regurgitation Collect a history and co
137、nduct a thorough physical examination Complete a neurological examination Observe the patient eating, to assess the likely stage of the swallowing process affected Plain radiography of pharynx and oesophagus Possible contrast studies - barium swallow and fluoroscopy Examination of oral cavity and ph
138、arynx under general anaesthesia Endoscopic examination of pharynx and oesophagus Possible diagnostic procedures for common alimentary symptomsVomiting* Collect a history and conduct a thorough physical examination* Characterize the vomitus produced* Is the vomiting primary or secondary?PRIMARY SECON
139、DARYHaematology and biochemistry Haematology and biochemistryPlain radiography UrinalysisContrast studies Specific tests of Endoscopy/ exploratory organ function laparotomyPossible diagnostic procedures for common alimentary symptomsDiarrhoeaDiarrhoea Collect a history and conduct a thorough physica
140、l examination Physical examination of the faeces produced Is the diarrhoea primary or secondary ? If primary, is the diarrhoea of small or large intestinal origin?PRIMARY SECONDARYSmall intestinal Large intestinal UrinalysisHaematology/biochemistry Faecal culture Specific tests of organ functionFaec
141、al culture Worm egg countWorm egg count Rectal examinationUndigested food analysis Plain radiographySerum folate/cobalamin Endoscopy/biopsyTrypsin-like immunoreactivityBreath hydrogen assaySugar permeability testUltrasound scanEndoscopy/exploratory laparotomy Possible diagnostic procedures for commo
142、n alimentary symptomsConstipation* Collect a history and conduct a thorough physical examination* Rectal examination* Neurological examination* Orthopaedic assessment* Plain radiography Possible diagnostic procedures for common alimentary symptomsFaecal tenesmus(里急后重）里急后重）Collect a history and condu
143、ct a thorough physical examinationRectal examinationFaecal culture and worm egg countPlain radiographyContrast studiesUltrasound scanEndoscopy/biopsy Possible diagnostic procedures for common alimentary symptomsAcute abdomenCollect a history and conduct a thorough physical examinationCareful abdomin
144、al palpationHaematology and biochemistryPlain radiographyPossibly contrast studiesParacentesisUltrasound scan Exploratory laparotomy Possible diagnostic procedures for common alimentary symptomsAbdominal enlargementCollect a history and conduct a thorough physical examinationCareful abdominal palpat
145、ionHaematology and biochemistryPlain radiographyParacentesis（腹腔穿刺）（腹腔穿刺）Ultrasound scanExploratory laparotomy Possible diagnostic procedures for common alimentary symptomsFAECAL ANALYSISPhysical appearanceInitial examination of a fresh fecal sample should concentrate on its physical appearance. In m
146、any cases of diarrhoea it is possible to decide whether it is associated with a small or large intestinal problem using the criteria shown in Table 8.1. Such a differentiation not only gives the clinician valuable information regarding the location of the lesion but consequently assists in the selec
147、tion of further appropriate diagnostic tests. Unfortunately, not all diarrhoeas may be readily classified, and features of both small and large intestinal disease may be present. This may reflect a small intestinal problem which results in the abnormal presence of nutrients or other agents in the la
148、rge intestine, thereby causing signs of large intestinal disease. Alternatively, it may reflect a condition that affects both the small and the large intestine equally. Table 8.1:Characteristics of faeces passed in small and large intestinal diarrhoea.Symptom/SignSmall intestineLarge intestineFaecal
149、 volumeIncreasedReducedFaecal tenesmusNonePresentFaecal bloodNone or changedOften presentFaecal mucusNoneOften presentUrgency（尿急）（尿急）RareOften presentDyschezia（排便困难）（排便困难）AbsentOften presentSteatorrhoea（脂肪痢）（脂肪痢）Often presentAbsentVomitingMay occurOccurs in 30% of casesWeight lossPresentAbsentFlatus
150、/borborygmi(肠鸣肠鸣)PresentRareCoat/skin conditionPoorNormalAppetiteIncreasedNormal or reducedFigure 8.2 Major causes of acute diarrhoeain dogs and cats.Endoparasitism: Hookworms钩虫钩虫 Whipworms鞭虫鞭虫Giardiasis贾第鞭毛虫病贾第鞭毛虫病Dietary indiscretions: Soiled foods Scavenging Over-eatingViral infections: Feline pa
151、nleucopenia猫瘟猫瘟 Canine parvovirus犬细小病毒犬细小病毒 Coronavirus冠状病毒冠状病毒Bacterial infection: Salmonellosis Campylobacter infection弯曲菌弯曲菌Intussusception肠套叠肠套叠Haemorrhagic gastroenteritisFigure 8.3:Major cause of chronic diarrhoea in dogs and cats. Small intestinal disease: Lymphocytic-plasmacytic enteritis淋巴细
152、胞-浆细胞性肠炎 Eosinophilic enteritis Lymphangiectasia淋巴管扩张 Lymphosarcoma淋巴肉瘤 GiardiasisExocrine pancreatic insufficiency (EPI)Colitis: Lymphocytic-plasmacytic Eosinophilic Histiocytic Granulomatous LymphosarcomaSystemic disease: Hyperthyroidism (cats) Hypoadrenocorticalism Hypothyroidism (dogs) Chronic r
153、enal failure Hepatic disease FeLV, FIV and FIP Melaena（黑黑粪粪症症） can be defined as the presence of changed blood in the faeces. The appearance of melaena will depend on the extent of bleeding and its location, but malaenic faeces normally appear black and tarry in consistency. This appearance is norma
154、lly associated with bleeding into the small intestine, although melaena may originate from the stomach or from the oesophagus, pharynx, mouth or respiratory system. In the latter cases blood is swallowed and passes through the alimentary tract to appear as melaena, giving the impression of alimentar
155、y disease. Patients with clotting disorders may present with melaena, but again careful clinical examination should reveal bleeding from other locations, confirming a generalized disorder.Occult blood（潜潜血血）refers to the presence of microscopic amounts of blood that can only be detected by laboratory
156、 analysis. Great care is required in interpreting a positive result in dogs and cats as they are often fed meat-based diets. The presence of haemoglobin or myoglobin in the diet will give false positive results. It is therefore important to place the patient on a meat-free diet for a minimum of 3 da
157、ys prior to testing for occult blood. A true strong positive result indicates only that bleeding is occurring somewhere along the alimentary tract.Culture for bacteriaNormal flora The small intestine lies between the almost sterile stomach (due to gastric acid) and the large bacterial population loc
158、ated in the colon. Bacterial numbers in the proximal small intestine are low but numbers increase in the ileum. The actual numbers present in any individual will vary depending on various internal and external factors. Many of the normal flora are beneficial to the animal by producing vitamin K, bio
159、tin, folate and short-chain fatty acids (SCFAs). If the numbers of bacteria present in the small intestine increase, small intestinal bacterial overgrowth (SIBO) develops. Such a proliferation of bacteria can seriously damage the intestinal mucosa. The point at which bacterial populations induce cli
160、nical signs of SIBO will vary with each individual and the genus of bacteria present. Pathogenic bacteria Pathogenic bacteria may establish when there is interference with the normal physiological regulation of the resident flora. Bacterial properties that permit pathogens to establish include: the
161、presence of flagellae; production of enzymes such as proteases; the ability of bacteria to adhere to the mucosa; and production of factors that interfere with intestinal motility. The abilities to produce enterotoxin and to invade enterocytes significantly increase pathogenicity. Potential pathogens
162、 include Salmonella, Campylobacter, Yersinia and Clostridium species and Escherichia coli. Analysis for viruses Canine parvovirus (CPV-2) infection usually results in an acute enteritis with secondary bacterial infection, involving especially Salmonella and Campylobacter spp. A definitive diagnosis
163、of parvovirus infection requires collection of a fresh faecal sample for viral antigen detection. Ideally, samples should be collected within the first 2 days of infection when the largest number of virus particles are present. A commercial ELISA test kit is available for the detection of parvovirus
164、 antigen in faeces. Serology can also be carried out in order to detect a rising titre of antibody indicating recent parvovirus infection. EndoparasitesEndoparasitic infection with roundworms (Toxocara canis Toxocara cati, Toxascaris leonina) and tapeworms (Dipylidium caninum, Taenia spp.and Echmoco
165、ccus) are, in the authors experience, very rare causes of diarrhoea in dogs and cats. However, Echinococcus and Toxocara both carry a significant public health risk and should be identified and treated whenever possible. Faecal smears Fresh faecal smears provide a quick and cheap method of examining
166、 faecal samples. However, as there is no concentration of ova it is easy to miss parasite eggs or cysts that are present in small numbers. A fresh fecal sample should be mixed with a small volume of physiological saline on a microscope slide. If protozoans are suspected, one drop of Lugols iodine wi
167、ll highlight these parasites but will reduce their motility. A negative result may be accurate or may reflect the small numbers of parasitic eggs present, intermittent excretion, or the effects of agents such as barium sulphate, kaolin, pectin or enemas. Faecal flotation Faecal flotation is a more s
168、ensitive method than the faecal smear for the detection of parasite eggs and cysl because the technique concentrates their numbers in a small volume of solution. Several methods have bee developed, but for the purposes of this chapter on two methods will be described. Faecal samples for detection of
169、 parasite eggs or cysts may be preserved b refrigeration at +4C for up to 2 days prior to examination, but should not be frozen. Preservation of faecal samples may also be carried out using 1 part faecel 3 parts preservative (1.5 g sodium acetate, 2 ml glacial acetic acid, 4 ml 40% formalin plus 92.
170、5 ml water). Hepatobiliary System IntroductionDiseases of the liver frequently present the small animal clinician with a diagnostic challenge; signs are often varied and vague and, despite a wide array of diagnostic tests of both hepatic damage and function, there is rarely a single test that identi
171、fies the problem definitively. For example, jaundice is often considered a cardinal sign of liver disease, yet can be caused by non-hepatic conditions (e.g. haemolysis, extrahepatic bile duct obstruction) as well as a range of different liver diseases. Conversely, significant liver disease can exist
172、 in the absence of jaundice. Nevertheless, following a thorough history-taking and careful physical examination, astute interpretation of a panel of laboratory tests in conjunction with radiographic and ultrasonographic imaging of the hepatobiliary system will often permit a presumptive diagnosis to
173、 be made. In most cases, however, with the exception of congenital portosystemic shunts (PSS), definitive diagnosis of primary liver disease will require histopathological examination of liver tissue. Figure 9.1: Some of the more common extrahepatic disorders that can cause abnormal liver test resul
174、ts. Acute pancreatitisDiabetes mellitusExocrine pancreatic insufficiencyExtrahepatic bacterial infectionHyperadrenocortisolismHyperthyroidismHypoadrenocorticismHypothyroidismImmune-mediated haemolytic anaemiaInflammatory bowel diseaseProtein-losing enteropathyRight-sided heart failureSepticaemiaShoc
175、k Table 9.1:Clinicopathological abnormalities associated with disturbances of hepatobiliary function. FunctionAbnormal laboratory test resultassociated with liver dysfunctionCarbohydrate metabolism:Glucose homeostasisHyper- or hypoglycaemiaLipid metabolism:CholesterolFatty acidsLipoproteinsBile acid
176、sHypo- or hypercholesterolaemiaHypertriglyceridaemiaLipaemiaElevated bile acidsProtein metabolism:AlbuminGlobulinsCoagulation proteinsHypoalbuminaemiaIncreased acute phase proteins, immunoglobulinsCoagulopathiesVitamin metabolism? Decreased folate, cobalaminVitamin E, vitamin K may be reduced depend
177、ing on the diseaseImmunological functionsHyperglobulinaemiaIncreased acute phase proteinsDetoxificationHyperammonaemiaDecreased ureaHyperbilimbinaemiaCLINICOPATHOLOGICAL CHANGES IN LIVER DISEASE Consequences of hepatobiliary dysfunction The diverse functions of the hepatobiliary system are reflected
178、 in the diverse clinicopathological changes that can be found in liver disease (Figure 9.3). The defective metabolism and excretion of bilirubin, causing accumulation of circulating bilirubin and the development of jaundice, is often considered the hallmark of liver disease, but it is only one of ma
179、ny abnormal laboratory tests that may found in liver disease. Indeed, even hyperbilirubinaemia from biliary obstruction is usually associated with hypercholesterolaemia and elevations of cholestatic marker enzymes. Figure 9.3: Clinical signs of hepatobiliary disease. Depression, decreased appetite a
180、nd lethargy Stunting and weight loss Vomiting, diarrhoea, and grey acholic faeces Polydipsia and polyuria Ascites Icterus Altered liver size Bleeding tendency Abdominal pain (rare) Encephalopathy(脑病脑病)Correlation with clinical signs The clinical signs of liver disease are many and varied (Figure 9.3
181、) and may be related to specific laboratory abnormalities. Signs are often vague and not apparent until there is significant hepatic dysfunction, which is why laboratory testing is helpful in detecting and characterizing early liver disease. However, it must always be remembered that equally abnorma
182、l tests may be secondary to a primary systemic disease. For example, fatty infiltration of the liver in diabetes mellitus can cause increases in serum activities of liver specific enzymes in both dogs and cats, and can result in jaundice in cats. Depression and diminished appetite These signs are re
183、flections of disturbed metabolism in liver disease, but are not associated with specific laboratory test abnormalities. Anaemia of chronic disease may be present. Abnormal lipoprotein and cholesterol metabolism may occur. Hypoglycaemia is seen in end-stage disease and may be one of many factors prod
184、ucing the signs of liver failure usually attributed to accumulation of metabolic toxins. Stunting and weight loss Congenital PSS and juvenile hepatopathies are associated with stunting, but the biochemical disturbances responsible are multifarious. Hypoproteinaemia is often associated with muscle wa
185、sting. Gastrointestinal signs Grey, acholic faeces are seen in biliary obstruction, and are therefore associated with jaundice. Diarrhoea may be a reflection of hypoproteinaemia causing bowel oedema, although lack of luminal bile salts and portal hypertension are more likely causes. Polydipsia and p
186、olyuria These signs may be associated with low levels of serum urea, although other mechanisms, e.g. hypercortisolism, are involved in their pathogenesis. Ascites Hypoproteinaemia is a recognized cause of tissue fluid accumulation. However, ascites is more common than generalized oedema in liver dis
187、ease, suggesting portal hypertension in acquired liver disease is also an important factor.Icterus Hyperbilirubinaemia causes jaundice, and may be due to prehepatic (haemolysis) or posthepatic (biliary obstruction, biliary leakage) disease as well as primary intrahepatic causes. Liver size Diseases
188、causing altered liver size are listed in Figure 9.4, but there are no specific laboratory markers of liver size and many diseases are not associated with abnormal liver size. Lipaemia may correlate with fatty infiltration of the liver. Bleeding tendency Coagulation times are usually abnormal if seve
189、re liver dysfunction causes bleeding. Generalized bleeding and haemorrhage from hepatic peliosis (cats) and vascular tumours, such as metastatic haemangi-osarcoma, may result in regenerative anaemia. Hepatoencephalopathy This syndrome is caused by accumulation of toxins because of severe hepatic dys
190、function and/or porto-systemic shunting of blood. Hyperammonaemia is a sensitive and specific marker for the syndrome, although other metabolic disturbances are involved. DIAGNOSTIC APPROACH TO LIVER DISEASEIn most cases, a tentative diagnosis can be deduced from the results of laboratory tests in c
191、onjunction with imaging techniques. However, the definitive diagnosis of primary liver disease usually depends ultimately on histological examination of liver biopsy specimens. Primary extrahepatic causes of secondary liver disease will hopefully be identified before biopsy is undertaken. Thus a dia
192、gnostic approach to liver disease includes: Clinical history Physical examination Laboratory tests Examination of ascitic fluid Imaging: Radiography Ultrasonography Angiography Scintigraphy Liver biopsy.The aims of laboratory testing are: To identify and characterize any hepatic dysfunction To ident
193、ify possible primary causes of secondary liver disease To differentiate causes of icterus To evaluate potential anaesthetic risks To identify causes of anaemia of unknown origin To assess prognosis To assess the response to xenobiotics To monitor response to therapy. There is a wide range of laborat
194、ory tests available for assessing liver status, but they can be conveniently divided into four classes: General screening tests Markers of liver damage Liver function tests Prognostic indices. The tests routinely available to the practising veterinary surgeon and indications for their use will be di
195、scussed in detail, and more specialized tests mentioned only briefly. Urinary SystemTHE ROLE OF CLINICAL PATHOLOGY Clinical pathology tests in the evaluation of a patient for the presence of renal and/or urinary tract disease should be performed under the following circumstances: When primary or sec
196、ondary urinary system disease is suspected from the presenting signs, clinical history or physical examination When a patient has a disease in another organ system that is known to be potentially associated with concurrent or secondary renal or urinary tract disease When screening at risk patients a
197、s part of a general health check (e.g. as part of a geriatric screening programme, before general anaesthesia, or before administration of drugs that are known to be potentially nephrotoxic, such as non-steroidal anti-inflammatory drugs, aminoglycosides or oxytetracycline). The accurate diagnosis of
198、 renal and urinary tract diseases requires investigation by any or all of the following: Full history Full physical examination Imaging: Radiography - plain and contrast studies; sometimes dynamic studies, Ultrasonography Urinalysis Blood chemistry Haematology Microbiological culture and sensitivity
199、 testing Tissue biopsy Surgical examination at laparoscopy or laparotomy Post-mortem examination Urine should be analysed when: There is a change in its physical appearance, e.g. discoloration An animal passes frank blood in its urine An animal exhibits polydipsia An animal exhibits polyuria An anim
200、al exhibits urinary tenesmus An animal licks its external genitalia excessively An animal exhibits increased urinary frequency An animal is dehydrated An animal is vomiting An animal has signs of fluid accumulation in the abdomen (i.e. ascites) or peripherally (subcutaneous oedema) Primary or second
201、ary renal or urinary tract disease is suspected A urolith has been passed An animal exhibits pyrexia of unknown origin It is part of a routine screening test - juvenile, geriatric or before anaesthesia. Urinalysis includes one or more of the following : Physical examination: color, smell, turbidity,
202、content, volume, specific gravity Chemical examination: pH, proteinuria, acetone, glucose,urea Examination of sediment Bacterial culture Viral examination. Clinical pathology panel for urinary system diseasePlasma ureaBlood urea nitrogenPlasma creatinineUrea:creatinine ratioTotal plasma proteinPlasm
203、a albuminBlasma sodiumPalsma potassiumPlasma chloridePlasma calciumPlasma phosphateGlomerular function tests in dogs and catsEndogenous creatinine clearanceExogenous creatinine clearanceInulin （菊酚）（菊酚）clearanceIothalanate(碘酞酸盐）碘酞酸盐） clearanceFiltration fraction24 hour urine protein excretionUrine ph
204、osphate:urine creatinineRENAL AND URINARY TRACT DISEASES Acute renal failure （ARF） occurs when there is sudden onset (within hours) of oliguria or azotaemia or both together. There are many causes, categorized as follows: Pre-renal azotaemia: the kidneys produce a small volume of concentrated urine, which is a physiological response to a pre-renal problem Renal azotaemia: due to primary renal disease Post-renal azotaemia: due to diseases of the urinary excretory tract.
