SEROUS FLUID CHAPTER 12

Learning Objectives Upon completing this chapter, the reader will be able to Describe the normal formation of serous fluid. Describe four primary causes of serous effusions. Differentiate between a transudate and an exudate, including etiology, appearance, and laboratory tests. Differentiate between a hemothorax and a hemorrhagic exudate. Differentiate between a chylous and a pseudochylous exudate.

Learning Objectives (cont’d) State the significance of increased neutrophils, lymphocytes, eosinophils, and plasma cells in pleural fluid. Describe the morphologic characteristics of mesothelial cells and malignant cells. List three common chemistry tests performed on pleural fluid, and state their significance. State the common etiologies of pericardial effusions. Discuss the diagnostic significance of peritoneal lavage.

Learning Objectives (cont’d) Calculate a serum-ascites gradient, and state its significance. Differentiate between ascitic effusions of hepatic and peritoneal origin. State the clinical significance of the carcinoembryonic antigen and CA 125 tests. List four chemical tests performed on ascitic fluid, and state their significance.

Serous Membranes Line the closed body cavities Two membranes Pleural Pericardial Peritoneal Two membranes Parietal: lines cavity wall Visceral: lines organs in cavity Fluid between membranes Serous fluid: named for each location

Formation Purpose: provide lubrication between the two membranes Ultrafiltrate of plasma Produced by hydrostatic and oncotic (protein) pressure in the capillaries lining the membranes Normally, oncotic pressure is the same on both sides of the membrane; hydrostatic pressure causes the production Small amounts of excess fluid are absorbed by lymphatic capillaries

Formation and Absorption of Serous Fluid

Formation Disruption causes fluid buildup; termed effusion Causes: hydrostatic pressure increased from congestive heart failure; oncotic pressure decreased from hypoproteinemia; increased capillary permeability from inflammation, infection, malignancy; lymphatic obstruction from tumors

Pathological Causes of Effusions Disruption of the mechanisms of serous fluid formation and reabsorption Increased capillary hydrostatic pressure Congestive heart failure, salt and fluid retention Decreased oncotic pressure Nephrotic syndrome, hepatic cirrhosis Malnutrition, protein-losing enteropathy Increased capillary permeability Microbial infections, membrane inflammations Malignancy Lymphatic obstruction Malignant tumors, lymphomas, infection and inflammation, thoracic duct injury

Specimen Collection and Handling Collected by needle aspiration Thoracentesis: pleural cavity Pericardiocentesis: heart cavity Paracentesis: peritoneal cavity Abundant fluid collected >100 mL EDTA tube: hematology Sterile heparinized or polyanethol sulfonate (SPS): microbiology, cytology Clotted or heparin: chemistry, serology

Specimen Collection and Handling (cont'd) Specimens for pH must be kept on ice Concentrate fluid for microbiology and cytology by centrifuging 100 mL Chemical tests compared with blood tests drawn at the same time

Transudates and Exudates Primary classification of serous fluids Transudates: systemic disorder disrupts filtration and reabsorption, congestive heart failure, nephrotic syndrome Exudates: conditions affecting membranes, inflammation, infection, malignancy Differentiation important for further testing Transudates = little further testing

Laboratory Differentiation of Transudates and Exudates Appearance Clear Cloudy Fluid:serum protein ratio <0.5 >0.5 Fluid:serum LD ratio <0.6 >0.6 White blood cell count <1000/µL >1000/µL Spontaneous clotting No Possible Pleural fluid cholesterol <45 to 60 mg/dL >45 to 60 mg/dL Pleural fluid:serum cholesterol ratio <0.3 >0.3 Pleural fluid:bilirubin ratio Serum-ascites albumin gradient >1.1 <1.1

General Laboratory Tests Appearance Transudate versus exudate tests first Transudates: seldom tested further Exudates: microbiology, cytology, and tests for general symptoms Differentials performed routinely on cytocentrifuged specimens White blood cells (WBCs), normal tissue cells, malignant cells

Pleural Fluid Additional transudate versus exudate tests Appearance Pleural fluid cholesterol <60 mg/dL versus >60 mg/dL Fluid-serum cholesterol ratio <0.3 versus >0.3 Fluid-serum bilirubin ratio <0.6 versus >0.6 Appearance Normal: clear, pale yellow Turbid: WBCs, inflammation, infection Milky: chylous material from thoracic duct leakage, pseudochylous material from chronic inflammations

Pleural Fluid (cont’d) Bloody: hemothorax (trauma), hemorrhagic effusion (membrane) damage Differentiate: do a hematocrit on fluid >50% blood HCT is hemothorax: more blood Membrane damage: low blood Differentiate chylous and pseudochylous Chylous is triglycerides; stain with Sudan III Pseudochylous is cholesterol; polarize and crystals also seen in wet bright-field view

Correlation of Pleural Fluid Appearance and Disease Clear, pale yellow Normal Turbid, white Microbial infection (tuberculosis) Bloody Hemothorax, hemorrhagic effusion, pulmonary emboli, tuberculosis, malignancy Milky Chylous material from thoracic duct leakage Pseudochylous material from chronic inflammation Brown Rupture of amoebic liver abscess Black Aspergillus Viscous Malignant mesothelioma (increased hyaluronic acid)

Hematology Tests Differential: primary cells are neutrophils, lymphocytes, macrophages, eosinophils, mesothelial cells, plasma cells, and malignant cells Macrophages (scavengers) often the highest ↑ Neutrophils: bacterial infection, pancreatitis, pulmonary infarction ↑ Lymphs: TB, viral infections, autoimmune disorders, malignancy Eosinophils: trauma introducing air and blood, allergic reactions, parasites

Hematology Tests (cont’d) Mesothelial cells: single cell layer lines membranes, common to see in serous fluid, pleomorphic, dark blue cytoplasm, round nuclei, normal and reactive; “fried egg appearance” Reactive cells may be multinucleated

Hematology Tests (cont’d) Lack of mesothelial cells is significant in tuberculosis (TB), exudate covers membranes

Hematology Tests (cont’d) Pleural fluid: primary cancer cells Adenocarcinoma cells are large and irregular; small cell or oat cell carcinoma cells are small like lymph cells, mesothelioma cells are large

Hematology Tests (cont’d) Metastatic breast carcinoma cells seen in clumps Small cell carcinoma

Chemistry Tests Glucose: decreased in inflammations and infections, have blood comparison pH: <7.0 indicates need for chest tubes, <6.0 indicates esophageal rupture (gastric fluid) Adenosine deaminase elevated in TB and malignancy Amylase: elevated in esophageal rupture and malignancy

Significance of Chemical Testing of Pleural Fluid Glucose Decreased in rheumatoid inflammation Decreased in purulent infection Lactate Elevated in bacterial infection Triglyceride Elevated in chylous effusions pH Decreased in pneumonia not responding to antibiotics Markedly decreased with esophageal rupture ADA Elevated in tuberculosis and malignancy Amylase Elevated in pancreatitis, esophageal rupture, and malignancy

Microbiology and Serology Tests Gram stains and aerobic and anaerobic cultures on fluid, TB smears, and cultures Serology tests for autoimmune disorders Tumor markers for metastatic malignancy Carcinoembryonic antigen: gastrointestinal malignancy CA125: uterine and ovarian malignancy

Pleural Fluid Testing Algorithm

Pericardial Fluid Normally small amount: 10 to 50 mL Permeability of membranes from infection (pericarditis, endocarditis), malignancy, trauma produces exudates Transudates: hypothyroidism, uremia, immune disorders Detect by cardiac tamponade (compression) heard by physician

Pericardial Fluid (cont’d) Appearance: normal clear, pale yellow Turbid: infection, malignancy (also blood streaked) Bloody: accidental puncture, anticoagulants Milky: chylous and pseudochylous material Fluid-serum protein and LD ratios for transudate versus exudate differentiation WBCs >1000/μL is bacterial endocarditis

Pericardial Fluid (cont’d) Malignant cells are metastatic from lung and breast Gram stains and cultures for endocarditis often caused by previous respiratory infections TB smears and cultures done in AIDS

Pericardial Fluid (cont’d) Metastatic giant mesothelioma cell also seen in pleural fluid as a primary malignancy in persons with asbestos contact

Significance of Pericardial Fluid Testing Appearance Clear, pale yellow Normal, transudate Blood streaked Infection, malignancy Grossly bloody Cardiac puncture, anticoagulants Milky Chylous and pseudochylous material Differential Increased neutrophils Bacterial endocarditis Malignant cells Metastatic carcinoma Carcinoembryonic antigen Gram stain and culture Acid-fast stain Tubercular effusion Adenosine deaminase

Peritoneal Fluid Effusion between the peritoneal membranes is called ascites Fluid is often called ascitic fluid Transudates: hepatic origin (cirrhosis) Exudates: bacterial peritonitis from intestinal perforation, ruptured appendix, and malignancy

Peritoneal Lavage Performed to detect early abdominal bleeding and need for surgery Blunt trauma injuries Normal saline injected into cavity, withdrawn, and red blood cell (RBC) count performed RBC count >100,000 indicates blunt trauma case Radiographic procedures also available

Transudates and Exudates More difficult than pleural and pericardial fluids Serum-ascites gradient is best differentiation Serum and fluid albumin levels are measured; fluid level is subtracted from serum level; difference (gradient) > than 1.1 is a transudate (hepatic origin) Serum albumin 3.8 – fluid albumin 1.2 = 2.6 = hepatic transudate

Appearance Normal: clear, pale yellow Turbid: bacterial and fungal infections Green-brown color = bile Milky: chylous and pseudochylous with trauma and lymphatic blockage WBC count: normal 350 cells/μL Absolute neutrophil count: >50% of total WBC count or greater than 250 cells indicates infection Lymphocytes elevated in TB

Cellular Examination Cells: WBCs, mesothelial cells, macrophages (lipophages) Yeast cells and Toxoplasma gondii Malignant cells, often contain mucin vacuoles

Cellular Examination (cont’d) Malignant cells of prostate, gastrointestinal, and ovarian origin

Cellular Examination (cont’d) Psammoma bodies benign or cancer of thyroid and ovaries

Chemical Tests Glucose: below plasma levels = peritonitis and malignancy ↑ Amylase: pancreatitis, gastrointestinal perforation ↑ Alkaline phosphatase: intestinal perforation ↑ BUN, creatinine: ruptured bladder, accidental perforation

Microbiology Tests Gram stains and aerobic and anaerobic cultures Anaerobic cultures: inoculate blood culture bottle at bedside Acid-fast smear, adenosine deaminase and culture for TB

Serological Tests Tumor markers CEA CA 125 Presence of CA 125 antigen with a negative CEA suggests the source is from the ovaries, fallopian tubes, or endometrium Presence of CEA antigen suggests source is gastrointestinal