Chapter 9

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Chapter 9
2012-04-09 18:24:48
Animal Clinical Pathology

Animal Clinical Path - Chapter 9
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  1. · Chemical Chemistry
    Kidney Assays
    Blood urea nitrogen (BUN)
    measures the amount of urea nitrogen, a waste product of protein metabolism, in the blood
  2. Urea is formed by the
    liver and carried by the blood to the kidneys for excretion. Because urea is cleared from the blood stream by the kidneys, a test measuring how much urea nitrogen remains in the blood can be used as a test of renal function.
  3. There are, however, many factors besides renal disease that can cause BUN alterations, including
    • protein breakdown, hydration status, and liver failure.
    • elevated Normal blood urea nitrogen in the dog is between 6 and 27 mg/dl
    • Increased BUN
  4. An increase in the BUN level is know as
  5. An BUN may be caused by;
    • Impaired renal function
    • Congestive heart failure as a result of poor renal perfusion
    • Dehydration
    • Shock
    • Hemorrhage into the gastrointestinal track
    • Excessive protein intake or protein catabolism
  6. Increased BUN
    • Diseased or damaged kidneys cause an elevated BUN because the kidneys are less able to clear urea from the bloodstream.
    • In conditions in which renal perfusion is decreased, such as hypovolemic shock or congestive heart failure, BUN levels rise.
    • A patient who is severely dehydrated may also have a high BUN due to lack of fluid volume to excrete waste products.·
    • Because urea is an end product of protein metabolism, a diet high in protein, such as high-protein tub feeding, may also cause the BUN to increase.
    • Extensive bleeding inot the gastrointestinal (GI) tract will also cause an elevated BUN because digested blood is a source of urea.
  7. Decreased BUN·
    A decreased BUN may be seen in:
    • Liver failure
    • Malnutrition
    • Overhydration from prolonged intravenous fluids Pregnancy (due to increased plasma volume)
  8. Decreased BUN
    Because urea is synthesized by the liver, severe liver failure causes a reduction of urea in the blood.
  9. Just as deyhydration may cause an elevated BUN, overhydration causes a decreased BUN.
  10. Decreased BUN
    An assessment of the BUN is used as a gross index of glomerular function. Because the BUN is affected by numerous non-renal factors, it is a line sensitive indicator of declining renal function than serum creatinine.
  11. Decreased BUN
    Serum creatinine level is another way of determining kidney function. Creatinine is a protein produced by muscle and released into the blood. The amount produced is relatively stable in a given animal. The creatinine level in the serum is therefore determined by the rate it is being removed, which is roughly a measure of kidney function. If kidney function falls, the creatinine level will rise.
  12. Decreased BUN
    The normal serum creatinine in the dog is between 0.7 and 1.6 mg/dl
  13. Pancreatic Assays
    The pancreas is actually two organs, one exocrine and the other endocrine, held together in one stoma. The endocrine part of the pancrease is involved with carbohydrate metabolism through secretion of insulin (which lowers blood glucose levels) and glucagon (which elevates blood glucose) into the blood.
  14. Pancreatic Assays
    The exocrine part of the pancreas secretes and enzyme-rich juice that contains enzymes necessary for digestion into the small intestine.
  15. Pancreatic Assays
    • The three primary pancreatic enzymes are:·
    • Trypsin·
    • Amylase·
    • Lipase
  16. Exocrine – Trypsin
    Trypsin (trypsinase) is a proteolytic enzyme that aids digestion by catalyzing the reaction that breaks down the proteins of ingested food.·
  17. Exocrine – Trypsin
    Trypsin activity is more readily detectable in feces than in blood. Trypsin is normally found in the feces and its absence is abnormal
  18. Exocrine – Trypsin
    The Knox Test mixes feces with a gelatin (protein solution. If tripsin is present in the feces it will digest the protein and prevent the solution form becoming a gel.·
  19. Exocrine – Trypsin
    The x-ray film test uses the gel on an undeveloped x-ray film to test for the presence or absence of trypsin. The x-ray film is placed in a slurry of feces and bicarbonate. If the gel comes off the film during mixing, typsin is present.·
  20. Exocrine – Trypsin
    Fecal samples should not be more than 1 day old as bacteria will proliferate and produce their own proteolytic enzymes which will give false positive results.
  21. Serum Trypsin-Like immunoreactivity (TLI)·
    • Detects trypsinogen leakage into the blood (More accurate)
    • Determines exocrine pancreatic insufficiency (EPI)-Low TLI values·
    • High TLI values indicate pancreatitis and feline IBD.
  22. Cobalamine and Folate·
    • Cobalamine and folate concentrations determine small intestinal function.
    • Cobalamine(B12) absorbed in ileumo
    • Folate(Folic acid) is also produced by bacteria·
  23. Cobalamine and Folate
    Cobalamine and folate are absorbed in different parts of the intestines.·
  24. Cobalamine and Folate
    Low cobalamine levels indicate ileum problems. (IBD)· Low Folate levels indicate duodenum and jejunum problems·
  25. Cobalamine and Folate
    Increased Folate levels indicate Small intestinal bacterial overgrowth.
  26. Exocrine – Amylase
    Amylase’s function is to break down starches and glycogen in sugars. Increased levels of amylase appear in blood duing acute pancreatitis, flair-ups of chronic pancreaitis, or obstrucion of the pancreatic ducts. (Levels also from liver, intestines and pancreas)·
  27. Exocrine – Amylase
    The rise in blood amylase is not always proportional to the severity of pancreatitis.·
  28. Exocrine – Amylase
    Calcium-binding anticoagulants like EDTA should not be used if amylase determination will be run. Amylase requires the presence of calcium for its activity.
  29. Normal amylase in dogs is between 339 and 1007 IU/L
  30. Exocrine – Lipase
    Lipase’s function is to
    break down long-chain fatty acids of lipids. Increased levels of lipase appear in blood during episodes of pancreatitis. (Lipase also released from liver, kidneys, and intestines)·
  31. Exocrine – Lipase
    Test methods are usually based on the hydrolysis of an olive oil emulation into fatty acids using the patients plasma.· Lipase is more sensitive for detecting pancreatitis than amylase.·
  32. Exocrine – Lipase
    Calcium-binding anticoagulants like EDTA should not be used if lipase determinations will be run. Lipase requires the presence of calcium for its activity.· Normal lipase in dogs is between 267 and 1769 IU/L
  33. Exocrine – Lipase
    • Spec cPL (Canine pancreas specific lipase) Immunoassay test used to determine pancreatitis – 98% accuracy
    • Tests for specific pancreatic lipase
    • Does not measure liver and kidney lipase values as normal blood lipase values.
    • More specific lipase tests are performed to determine pancreatitis, because amylase and lipase levels increase in only 50-60% of all pancreatitis disease.
  34. Endocrine – Glucose
    • The endocrine part of the pancreas is made up of small microscopic clusters of cells called Islets of Langerhans. These islets features three main types of cells:
    • Alpha cells – secrete glucagon in response to low serum glucose
    • Beta cells – secrete insulin in response to high serum glucoseo
    • Delta cells – secrete the hormone somatostatin
  35. Endocrine – Glucose
    The blood glucose level is used as an indicator of carbohydrate metabolism in the body and to indirectly measure endocrine function of the pancreas.
  36. Endocrine – Glucose
    Glucose utilization depends on the amount of insulin and glucagon in the blood. As insulin levels increase, the blood glucose lowers. When insulin levels are decreased (as in Diabetes), blood glucose rises.
  37. Endocrine – Glucose
    Serum and plasma must be separated from the erythocytes immediately after blood is collected. RBCs continue to metabolize glucose after collection, lowing the glucose value by about 10% per hour. If samples cannot be separated immediately, it is best to use sodium fluoride as anticoagulant.
  38. Endocrine – Glucose
    • Normal glucose level in a dog is between 79 and 127 mg/dl·
    • Problems with insulin causes high blood glucose and the disease Diabetes.
  39. Endocrine – Glucose
    Type 1 Diabetes occurs due to immune system destruction of the insulin-producing (beta) cells of the pancreas. This is the predominant form of primary diabetes in dogs, but is rare in cats. There may be some genetic component to the cause of diabetes in dogs. Patients with this form of diabetes often must be treated with insulin injections.
  40. Endocrine – Glucose
    Type 2 Diabetes is characterized by obesity, loss of tissue sensitivity to insulin, and deposition of a precipitate called amyloid into the pancreatic islets. Type 2 diabetics animals may be producing no, too little, normal amounts, or even excessive amounts of insulin, but this insulin is failing to achieve its normal action. Type 2 diabetes is the most common form of diabetes in cats, but is rare in dogs.
  41. Endocrine – Glucose
    Type 3 Diabetes occurs with some other disease or condition damage the pancreas and/or prevents bata islet cell function. Severe necrotizing pancreatitis and pancreatic tumors cause type 3 diabetes.
  42. Endocrine – Glucose
    Diabetes is generally characterized by increased thirst (polydipsia), increase urination (polyuria), fatigue, weakness, and anorexia. Blood glucose level is high (hyperglycemia)
  43. Endocrine – Glucose
  44. Endocrine – Glucose
    • Depending on the level of hyperglycemia, glucose may be detected in the urine (glycouria)·
    • There are numerous secondary conditions that can occur from diabetes if it is not controlled including renal failure, liver failure, and poor circulation to extremities (with possible amputation)·
  45. Endocrine – Glucose
    Depending on its severity, diabetes may be treated with insulin-replacement therapy (insulin shots), or with corrective diet.
  46. Creatine Kinase (CK)·
    Previous name was creatine phopokinase (CPK)·
  47. In all mammals, CK is found in most abundance in striated muscle and therefore is extremely specific for muscle damage.
  48. Creatine Kinase (CK)·
    While specific to muscle, it cannot determine which muscles are damaged or indicate the severity of muscle damage.
  49. Creatine Kinase (CK)·
    Examples of muscle damage include intramuscular injections, myositis, persistent recumbency, surgery, vigorous exercise, electric shock, laceration, bruising, and hypothermia.
  50. Normal CK level in dogs is between 7 and 218 IU/L
  51. Plasma Proteins
    • There are over 200 plasma proteins.
    • The three most important commonly assayed types of proteins are
    • albumins,
    • globulins, and
    • fibrinogen.
  52. Plasma Proteins
    Albumins account for most (about 60%) of the plasma proteins. They are produced by th liver and provide osmotic pressure for maintaining blood volume and blood pressure. They are also important in binding and transporting other substances in the blood. Decreased albumin (hypoalbuminemia) is commonly seen in diffuse where production is impaired. In renal disease, albumin may be lost in the urine (proteinuria)
  53. Plasma Proteins
    Some types of globulins also produced by the liver. Most of these types transport lipids and fat-soluble vitamins in the blood. Others, known as antibodies, are produced by cells of the immune system. Globulins are roughly divided into alpha-1, alpha-2, beta, and gamma globulins. In general, alpha-1 and alpha-2 proteins levels increase in the presence of inflammation.
  54. Plasma Proteins
    Fibrinogen, which accounts for only about 4% of the total plasma proteins, is an important clotting faction produced by the liver.
  55. Total Proteins
    Total proteins (TP) in a measure of all plasma proteins in the blood, including fibrinogen. The TP may be affected by altered hepatic synthesis, altered protein distribution, and altered protein breakdown or excretion, dehydration, or over-hydration.
  56. Total Proteins
    Total proteins determinations are made in practice with the use of the Refractometer. Normal TP in dogs is between 5.5 and 7.5 mg/dL.
  57. Total Proteins
    Fibrinogen is often determined using the Heat Precipitation Fibrinogen test. Acute inflammation often elevates fibrinogen.
  58. Serum Electrophoresis·
    The level of individual proteins (fractions) in serum can be determined in commercial laboratories.
  59. Serum Electrophoresis·
    • The most common method is via serum electrophoresis.·
    • This method is based on the fact at a certain pH, all serum proteins are negatively charged, but the degree of that charge varies with each type of protein.
  60. Serum Electrophoresis·
    Serum proteins can be separated by placing serum on special paper or in a gel and applying an electrical charge. The positive charge draws the proteins toward the positive pole at different rates depending on the degree of their negative charge.
  61. Serum Electrophoresis·
    • Protein migrate in the following order:o
    • Albumin
    • Alpha globulins (increased during inflammation)
    • Beta globulins
    • Gamma globulins
  62. Serum Electrophoresis·
    Most antibodies are gamma globulins therefore gamma globulins become ore abundant following infections or immunizations
  63. Serum Electrophoresis·
    If an antibody-secreting cell, called a plasma cell, becomes cancerous, it grows into a clone secreting single kind of antibody molecule. This type of cancer is called a plasma cell myeloma.
  64. Electrolyte Assays·
    Electrolytes are salts in the body that conduct electricity and are found in the body, fluid, tissue, and blood.

    Examples are: Sodium Potassium Calcium Magnesiumo Chloride Bicarbonate
  65. Electrolyte Assays·
    Sodium & Potassium
    Sodium (Na+) is concentrated in the extracellular fluid between tissue cells and potassium (K+) is concentrated in the intracellular fluid within cells. Proper balance is essential for muscle coordination, heart function, fluid absorption and excretion, nerve function, and concentration.
  66. Electrolyte Assays·
    Sodium & Potassium
    The kidneys regulate fluid absorption and excretion and maintain a narrow range of electrolyte fluctuation. Normally, sodium and potassium are filtered and excreted in the urine and feces according to the body’s needs. Too much or too little sodium or potassium, caused by poor diet, dehydration, medication, and disease, results in an imbalance. Too much sodium is called hyperNAtremia; too little is called hypoNAtremia. Too much potassium is called hyperKalemia; too little is called hypoKalemia.
  67. Electrolyte Assays·
    Calcium (Ca) is primarily tied to bone density but it has many other functions. Ca has major roles in nerve function, muscle contractions, cardiac muscle contractions, hormone release and function of body cells.
  68. Electrolyte Assays·
    Ca and phosphorus have an inverse relationship.o High blood Ca is called hypercalcemia. Low blood Ca is called hypocalcemia.
  69. Electrolyte Assays·
    Normal Ca in dogs is between 8.9 and 11.5 mg/dLo EDTA or oxalate anticoagulants should not be used when collecting blood for Ca assay because they bind with Ca and make it unavailable for assay.
  70. Electrolyte Assays·
    The parathyroids are endocrine glands involved with calcium balance. They secrete parathormone (PTH) is response to low serum Ca+ and secrete less PTH with the Ca+ is normal or high. PTH and Vit D causes Ca+ to come out of bone and enhance intestine absorption of Ca+ and phosphorus. (PTH causes an increase in calcium).
  71. Electrolyte Assays·
    If the parathyroids become cancerous, their constant secretion of parthormone leads to marked Ca+ removal form the bones (osteomalacia). Osteomalacia characterized by soft and thin bones and teeth, and frequent, easy fractures.
  72. Electrolyte Assays· Calcium
    Kidney damage can result in parathyroid hyperactivity (due to phosphorus retention) and thus also lead to osteomalacia. This condition is called Renal Secondary Hyperparathyroidism.
  73. Electrolyte Assays
    • Magnesium is needed for utilization of ATP
    • Primarily in bone and skeletal muscle
    • Only 1% in blood
    • Hypomagnessmia
    • Hypokalemia – non resolving with supplemantation
    • Hypocalemia – hypoparathyroid disease
    • Myopathy and neuropathy – critically ill
    • Convulsions and cardiac arrest if severe
  74. Electrolyte Assays
    • Potassium is an intracellular electrolyte
    • Potassium needed for normal kidney function
    • Sodium/Potassium pump·
    • High sodium intake decreased potassium due to excretion.
  75. Electrolyte Assays
    • Potassium has function in cardiac, skeletal, muscle and digestive disease
    • Causes of Potassium deficiency as vomiting, diarrhea and diuretic
    • Hypokalemia
    • Symptoms – weakness, lethargy, muscle cramps, arrhythmias and walking abnormalities in cats.