Clin Path Assimilation: Digestive-related focus - PDF

Lecture Objectives Know the principles of a problem-based approach to diagnosis Apply the problem-based approach to a case Know the basic nose to tail anatomy of the gastrointestinal tract and hepatobiliary system Compare modifications to the gastrointestinal tract in different veterinar...

Lecture Objectives Know the principles of a problem-based approach to diagnosis Apply the problem-based approach to a case Know the basic nose to tail anatomy of the gastrointestinal tract and hepatobiliary system Compare modifications to the gastrointestinal tract in different veterinary species Explain the importance of anatomy to clinical veterinary practice  Problem-Based Approach to Cases What is a problem? Abnormal finding History, PE, Diagnostics How does it work? 1 Baseline Data 2 Problem List 3 Ddx List 4 Dx Plan 5 Problem List 6 Working Dx 7 Tx Plan Problem-Based Approach to Cases Step 1—Collect baseline information Signalment History Current episode Previous illness Management Physical examination Triage 1st esp if ER Systematic, complete PE Case Example Sadie 10 year old, female spayed, Sheltie Presenting for a 3 day history of vomiting and anorexia Sadie—Physical Examination Findings T=100.4 P=100 R=32 CRT= 25% in response to inflammatory cytokines Positive APPs = increase production Sensitive indicator of inflammatory disease Negative APPs = decrease production/release Acute-Phase Proteins (APPs) Positive = ↑ (1-2d) Negative = ↓ (hours-days) Fibrinogen Albumin C-reactive protein (CRP) Transferrin Serum amyloid A (SAA) Haptoglobin (Hpt) Ceruloplasmin (Cp) α2-macroglobulin (A2MG) α1-acid glycoprotein (AGP) Complement (C3, C4) https://eclinpath.com/chemistry/proteins/acute-phase-proteins/ Main APPs by Species (FYI) Species Major APP: Moderate APP: ↑100-1000 fold ↑5-10 fold Peak 24-48h Peak 48-72h Cat SAA AGP, Hpt Dog CRP, SAA Hpt, AGP, Cp Horse SAA Hpt, Fibrinogen Cattle Hpt, SAA AGP, CRP Pig Hpt, SAA, CRP, Pig-MAP AGP Mouse SAA Hpt, AGP Rat A2MG Hpt, AGP https://eclinpath.com/chemistry/proteins/acute-phase-proteins/; https://onlinelibrary.wiley.com/doi/10.1111/vcp.13220 4-6 bands/fractions: PA Alb Prealbumin Albumin Albumin Protein Electrophoresis α1LP α1AT α1-lipoprotein (HDL) α1-antitrypsin α-globulins α1ACT α1-antichymotrypsin β-globulins Tracing (FYI) α2MG Hpt α2-macroglobulin Haptoglobin Tf Transferrin γ-globulins βLP C3 β-lipoprotein (LDL) Complement + –Sample applied +APP –APP Stockham & Scott; https://www.dreamstime.com/illustration/antibody.html  [Foundations 2A] Inflammation Recall: CBC Findings WBC number & morphology What about RBCs? Sick animals may also be stressed, how might this be reflected in CBC? Chemistry?  [GI 1] Protein Aberrations Hyperproteinemia Hypoproteinemia Hemoconcentration ↑ protein loss ↑ Albumin + Globulin ↓ protein synthesis ↑ Globulin synthesis ↑ protein catabolism Inflammation (infectious, noninfectious) Failure of passive transfer Lymphoid neoplasia (B cell, foals, calves: colostrum! plasma cell) Hemodilution e.g., iatrogenic, edematous disease–congestive heart failure, cirrhosis  Hypoproteinemia DDx: ↑ Loss Non-Selective Selective ↓ Albumin & ↓ Globulin ↓ Albumin Panhypoproteinemia Protein-losing nephropathy (PLN) Blood loss (hemorrhage) Glomerular damage* Concurrent lab findings? Proteinuria +/- azotemia, isosthenuria Protein-losing enteropathy (PLE) Nephrotic syndrome: hypoAlb, hyperChol +/- edema/effusions Generalized mucosal disease Lymphatic disease Protein-losing dermatopathy (PLD) Lymphangiectasia: hypoChol, lymphopenia Severe bite wounds, burns, skin GI blood loss (parasites, neoplasia) infections, etc. Hypoproteinemia DDx: ↓ Production Hypoproteinemia DDx: ↑ Catabolism Hepatic insufficiency/failure (↓ Alb) Cirrhosis, necrosis, inflammation, PSS, neoplasia Concurrent lab findings? Malabsorption or maldigestion Intestinal mucosal +/- lymphatic disease, EPI Inflammation (↓ Alb) Negative acute-phase response Lymphoid hypoplasia/aplasia (↓ Glob): Immunodeficiency (congenital, acquired) Cachexia (severe): Chronic diseases, neoplasia, malnutrition, starvation Protein & Microvascular Fluids WATER = 60% body weight 2/3 intracellular (ICF) 1/3 extracellular (ECF) 80% interstitium 20% plasma/blood Moves through inter-endothelial pores Pores large enough for small nutrients (ions, glucose, AAs), waste; too small for cells, large proteins (albumin) Passive in response to concentration and pressure gradient In health, composition of plasma and interstitial fluid is similar (minus large plasma proteins) Starling Forces Water distribution determined by osmotic/oncotic and hydrostatic pressure differentials between plasma and interstitium [Plasma proteins (namely albumin)] Abnormal Fluid Distribution Imbalance between intravascular and interstitial compartments Mechanisms Increased (micro)vascular permeability Increased intravascular hydrostatic pressure Decreased intravascular colloidal osmotic (oncotic) pressure Decreased lymphatic drainage Manifestations Interstitial edema Cavitary effusion Intracellular edema Hypervolemia  [Clinical Skills 2B; “Effusion” module] Effusions: Main Types Characterized by cellularity and protein concentration Cytology +/- biochemical testing can facilitate underlying process(es) Transudate: ↑ plasma hydrostatic pressure (e.g., portal hypertension), or ↓ plasma oncotic pressure (↓ albumin) → leakage of fluid from capillaries Lowly cellular, poorly proteinaceous fluid Exudate: ↑ vascular permeability (inflammatory mediators) → leakage of fluid from capillaries + recruitment/chemotaxis of inflammatory cells Highly cellular, highly proteinaceous fluid  Effusions: Special [FYI] Can also occur due to vessel or viscus rupture or leakage Variable cellularity & protein Examples: Dx Causes Hemorrhagic PCV/HCT >1%; 25% of peripheral blood Trauma, neoplasia, hemostatic defects Lymphorrhagic Chylous: Triglyceride >100mg/dL, >2x serum Cardiac disease, trauma, neoplasia, Non-chylous: Cholesterol > serum idiopathic Uroperitoneum Creatinine >2x serum; Potassium > serum Trauma, urolith, neoplasia Bile peritonitis Bilirubin >2x serum Trauma, cholelith, inflamm, neoplasia Septic (e.g., GI) GI flora (bacteria, ciliates, etc) Perforation, obstruction, ischemia, Glucose < serum (>20 mg/dL diff) trauma, neoplasia, abscess Lactate > serum (3.0 >3000 Neutrophils Degenerate neutrophils, bacteria Chylous Variable Variable Mostly lymphs Grossly milky white; high TG; low CHOL Hemorrhagic >3.0 Variable Similar to blood Erythrophagia +/- hemosiderin in macrophages Neoplastic >2.5 Variable Neoplastic cells Criteria of malignancy Protein Summary: Test Yourself Disease Albumin Globulins Protein-losing nephropathy (PLN) Protein-losing enteropathy (PLE) Hemorrhage Liver dysfunction Inflammation Dehydration/hemoconcentration Lymphoid neoplasia Electrolytes  [GI 1] Abnormal electrolyte concentrations in blood Can result from 1 or more of these basic processes: Changes in free water Decreased or increased intake Shifts to and from ICF ICF = K+ rich ECF = Na+, Cl- rich Increased retention via the kidney Increased loss via the kidney, GI tract, skin, or airways These changes can create acid-base abnormalities (select primary conditions touched on in GI…)  [GI 1] Sodium and Water Blood volume and plasma osmolality regulation affect serum sodium Water and sodium intricately associated Serum sodium is indication of amount of sodium relative to water in ECF Can be used to infer total body sodium if consider hydration status and ECF volume  [GI 1] Concentration Changes: Sodium vs Water Sodium Aberrations Thrall, Veterinary Hematology and Chemistry, 2012  [“GI handling of electrolytes” module] Chloride Sodium and Chloride tend to move in parallel Na–Cl difference 30-40 = proportionate Similar DDx for aberrations >40 = disproportionate (less Cl) Loss or Sequestration Vomiting of gastric contents; upper gastrointestinal obstruction; gastric dilatation- volvulus (GDV); displaced abomasum (DA) or abomasal atony Chloride has inverse relationship with Bicarbonate Cursory Acid-Base Review Metabolic component Primarily regulated by kidney *HCO3 ≈ tCO2 (not exactly the same but can think of as similar) Status measured by Bicarbonate (HCO3-) ↑ HCO3 = Alkalosis (most commonly caused by loss or sequestration of HCl) ↓ HCO3 = Acidosis Loss of HCO3-containing fluids (e.g., diarrhea) = Secretional Buffering of organic acids (e.g., lactate, ketones) = Titrational, aka High Anion Gap Respiratory component Regulated by ventilation (lungs) Status measured by pCO2 (increased = acidosis; decreased = alkalosis) Anion Gap Thrall, Veterinary Hematology and Chemistry, 2012 Anion Gap Thrall, Veterinary Hematology and Chemistry, 2012 Miscellaneous Reminders/Points Minerals and GI Calcium and phosphorus absorbed in GI Mediated by vitamin D (except in horses) Conversion to active form via Liver, kidney Calcium = ileum Absorption also influenced by acidity (acidifying substances promote absorption), calcium-chelating dietary components/drugs (e.g., oxalate, phosphate, phytate), intestinal epithelium health Absorption inhibited by corticosteroids Excretion: kidney >>> feces Phosphate = jejunum; colon/cecum (horses) Absorption enhanced by low dietary calcium, increased dietary acidity, growth hormone Absorption decreased by high Ca:P diet, antacids Excretion: kidney > feces (ruminants: saliva >> feces)  Test Yourself Hormone Calcium Calcium Homeostasis Calcitonin PTH Vitamin D3 Calcium in ECF: 10 50 40 Free "ionized" Protein-bound Complexed with nonprotein anion Stockham & Scott, Fundamentals of Vet Clin Path Calcium Aberrations: General Mechanisms HyperCalcemia HypoCalcemia Increased protein-bound Ca (rare) Decreased protein-bound Ca** Increased bone mobilization Inadequate bone mobilization Increased intestinal absorption Inadequate intestinal absorption Decreased urinary excretion Excess urinary excretion Increased PTH, Increased Decreased PTH, Decreased Vitamin D Vitamin D *Young animals (