EDEMA Learning Objectives Define edema Recognize and be able to describe the gross and microscopic appearance of edema Know the four pathophysiological mechanisms by which edema develops Understand the different mechanisms under which generalized and localized edema develop Know the terminology for edema/fluid accumulation in different tissues / regions of the body Understand the clinical significance and pathogenesis of edema at important sites (eg lung and brain) Understand the clinical significance, gross appearance, and pathogenesis of dehydration
Circulatory Disturbances 1: Introduction and Edema Shannon Martinson, January 2017 http://people.upei.ca/smartinson/ VPM 152 General Pathology
INTRODUCTION NORMAL CIRCULATORY SYSTEM Important concepts Distribution of fluid is carefully controlled (homeostasis) Deviations from normal can have profound pathological effects Normal function requires intact blood and lymph vessels Endothelial cells are important!
INTRODUCTION NORMAL CIRCULATORY SYSTEM Components of the Circulatory System Collection system Pump Distribution system Microcirculation system
INTRODUCTION NORMAL CIRCULATORY SYSTEM Components of the Circulatory System
INTRODUCTION NORMAL CIRCULATORY SYSTEM Endothelial cells All components of the circulatory system are lined by a single layer of endothelium Endothelial cells affect: Fluid balance Hemostasis Inflammation / immunity Angiogenesis / healing Image: Zachary PBVD 2017
INTRODUCTION NORMAL CIRCULATORY SYSTEM Microcirculation Capillaries Image: Mescher, Junqueira s Basic Histology, 12 ed volume: 1300 x crosssectional area of aorta Normally contain only ~5% of the blood Site where nutrients & wastes are exchanged Critical site for fluid balance
INTRODUCTION NORMAL CIRCULATORY SYSTEM Mechanisms for transport of substance across capillary walls Capillary wall is semipermeable membrane Direct diffusion Most small molecules move by passive diffusion through endothelial cell membrane or interendothelial pores Normal interendothelial pores too small to allow escape of large proteins* With inflammation endothelial cells contract, allowing larger molecules to escape* Water, Ions, Glucose, Amino acids Gas Lipid soluble molecules
INTRODUCTION NORMAL CIRCULATORY SYSTEM Mechanisms for transport of substance across capillary walls Capillary wall is semipermeable membrane Transcytosis With some endothelial cells, fluids / macromolecules can be transported across a cell by vesicles
INTRODUCTION NORMAL CIRCULATORY SYSTEM Fluid distribution and Homeostasis Total Body Water 60% 20% 40% Extracellular Fluid Intracellular fluid 5% Plasma Interstitial fluid 15%
INTRODUCTION NORMAL CIRCULATORY SYSTEM Interstitium The space between microcirculation and the cells Function Binds cell/structural elements into discrete tissue and organs Medium through which metabolic products pass between circulation and cells Structure Composed of extracellular matrix (ECM) and supporting cells ECM provides structural support and has adhesive absorptive properties
INTRODUCTION NORMAL CIRCULATORY SYSTEM Extracellular Matrix Structural molecules: Collagen, reticulin & elastin fibers Ground substance: Adhesive glycoproteins (eg fibronectin, laminin) Absorptive glycosaminoglycans / proteoglycans Image: Zachary PBVD 2017
INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Distribution of fluids, nutrients & wastes between blood interstitium cells controlled by physical structures, pressure gradients and ion concentration gradients
INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Capillaries (endothelial cells + basal lamina): Allow the free passage of H 2 O & ions Oppose the passage of plasma proteins Water distribution between plasma & interstitium is primarily determined by hydrostatic and osmotic pressure differences between the two compartments. Water Ions Protein Hydrostatic pressure is the pressure exerted by a fluid in a confined space The osmotic pressure exerted by proteins is referred to as oncotic pressure
Distribution of Fluids INTRODUCTION NORMAL CIRCULATORY SYSTEM Hydrostatic pressure in the vascular system + interstitial osmotic pressure moves fluid out of the vascular system Starlings Equation Plasma hydrostatic pressure Tissue colloidal osmotic pressure
Distribution of Fluids INTRODUCTION NORMAL CIRCULATORY SYSTEM Starlings Equation The osmotic pressure of the plasma proteins and tissue hydrostatic pressure contains the fluid within the vascular system. Plasma hydrostatic pressure Tissue colloidal osmotic pressure Plasma colloidal osmotic pressure Tissue hydrostatic pressure Hydrostatic pressure drops along the length of the capillary bed!
Distribution of Fluids INTRODUCTION NORMAL CIRCULATORY SYSTEM Starlings Equation Hydrostatic pressure drops along the length of the capillary bed!
INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Starlings Equation Net movement of fluid out of the capillaries Plasma hydrostatic pressure Tissue colloidal osmotic pressure Plasma colloidal osmotic pressure Tissue hydrostatic pressure Excess fluid is drained via lymphatics Excess fluid Lymphatic drainage
CIRCULATORY DISTURBANCES Edema Hyperemia and congestion Shock Hemorrhage Thrombosis and embolism Infarction
EDEMA EDEMA Abnormal (excess) accumulation of fluid in interstitial tissue spaces or body cavities Edema in the stomach wall Gross Appearance of Edema Organs wet (± gelatinous) and heavy Organs swollen and fluid may weep from cut surface Fluid present in the body cavities
EDEMA Histologic Appearance of Edema Lightly staining eosinophilic fluid (if some protein content) Clear / no staining (if protein content low) Lymphatics usually dilated Edema in the stomach wall
EDEMA Edema 4 Pathophysiological Mechanisms of Development 1) Intravascular hydrostatic pressure hronic local passive hyperemia 2) Plasma colloidal osmotic pressure 3) Lymphatic drainage 4) Vascular permeability
EDEMA - Pathophysiological Mechanisms of Development 1. Increased intravascular hydrostatic pressure NORMAL Due to impaired venous blood flow Generalized edema: eg Heart failure** Localized edema: eg tight bandage causing local obstruction of venous return
EDEMA - Pathophysiological Mechanisms of Development 2. Decreased plasma colloidal osmotic pressure Plasma colloidal osmotic pressure is exerted mostly by plasma protein NORMAL Due to hypoproteinemia Proteins not produced Liver disease Proteins lost Kidney (glomerular) disease Intestinal damage Proteins not absorbed Starvation Malabsorption Causes generalized edema
EDEMA - Pathophysiological Mechanisms of Development 3. Decreased lymphatic drainage NORMAL Due to lymphatic obstruction / damage Surgery / trauma (fibrosis) Neoplasm (tumour) or mass Inflammation (lymphangitis) Typically localized
EDEMA - Pathophysiological Mechanisms of Development 4. Increased vascular permeability/ Endothelial damage NORMAL Increased permeability Mostly due to inflammatory / immune reactions release of inflammatory mediators inflammatory edema Endothelium can also be directly damaged by specific agents (eg viruses, toxins)
EDEMA - Pathophysiological Mechanisms of Development 1) Blood hydrostatic pressure 2) Plasma colloidal osmotic pressure 3) Lymphatic obstruction 4) Vascular permeability Transudate: Low protein content <30g/L Low specific gravity <1.025 Few nucleated cells <1.5x 10 9 / L Fluid Characteristics: Exudate: High protein content > 30g/L High specific gravity > 1.025 High nucleated cells > 7 x 10 9 / L
Localized Edema LOCALIZED VS GENERALIZED EDEMA Mechanisms of Development Local impaired venous drainage Local lymphatic blockage Local inflammation
LOCALIZED VS GENERALIZED EDEMA Generalized Edema Mechanisms of Development Increased hydrostatic pressure Heart failure Decreased colloidal osmotic pressure Hypoproteinemia Common locations: Abdominal cavity (= ascites) Thoracic cavity (= hydrothorax) Dependent subcutaneous edema Subcutis on the ventrum of the abdomen / thorax ( brisket edema ) Subcutis of the ventral cervical / mandibular region ( bottle jaw ) Subcutis of the limbs ( stocking up )
Generalized Edema LOCALIZED VS GENERALIZED EDEMA
TERMINOLOGY OF EDEMA vet.uga.edu Pitting edema When pressure is applied to an area of edema and a depression or dent results
TERMINOLOGY OF EDEMA Anasarca Severe and generalized edema with profound subcutaneous tissue swelling
TERMINOLOGY OF EDEMA Hydrothorax Non-inflammatory fluid (transudate) in the thoracic cavity
TERMINOLOGY OF EDEMA Hydropericardium Non-inflammatory fluid (transudate) in the pericardial sac
TERMINOLOGY OF EDEMA Hydroperitoneum = Ascites Non-inflammatory fluid (transudate) in the peritoneal cavity
CLINICAL SIGNIFICANCE OF EDEMA Dependent upon: 1. Extent: mild < moderate < marked / severe 2. Location: skin < lung < brain 3. Duration: acute vs chronic Increase in fibrous connective tissue after prolonged edema
PULMONARY EDEMA Pulmonary edema Accumulation of fluid in interstitium and alveoli of the lungs Common cause of death in many disease processes Normal lung Pulmonary edema
PULMONARY EDEMA Mechanisms of development 1. Circulatory failure Increased hydrostatic pressure: especially left sided heart failure Flooding of the alveolar spaces with transudate
PULMONARY EDEMA Mechanisms of development 2. Damage to the pulmonary capillary endothelium Usually with acute inflammation (inflammatory edema) or toxins If increased vascular permeability is substantial and widespread death (ARDS acute respiratory distress syndrome)
PULMONARY EDEMA Gross appearance: Lungs are heavy and wet Interlobular septa are distended with fluid Froth in airways on cut surface
PULMONARY EDEMA Gross appearance: Lungs are heavy and wet Interlobular septa are distended with fluid Froth in airways on cut surface
PULMONARY EDEMA Histologic appearance: Fluid in interstitium / alveolar spaces Dilated pleural / septal lymphatics Often pink (proteinaceous) Normal lung
PULMONARY EDEMA Chronic pulmonary edema Chronicity fibrosis of pleura & alveolar septa Most commonly seen with cardiac failure and accompanying pulmonary congestion
CEREBRAL EDEMA Causes Trauma to brain Obstruction of venous outflow Intracranial inflammation Gross appearance Brain is heavier than normal Sulci are narrow Gyri are swollen and flattened http://ocw.tufts.edu
CEREBRAL EDEMA Cerebellar coning Herniation of the cerebellum through the foramen magnum Zachary, PBVD, 2017
CEREBRAL EDEMA Cerebral herniation Herniation of caudal cerebral cortex beneath the tentorium cerebelli Normal Zachary, PBVD, 2017
CEREBRAL EDEMA Histologic appearance Expansion of the Virchow-Robin spaces Normal Zachary, PBVD, 2017
DEHYDRATION Dehydration Deficiency of water (imbalance between uptake and loss of water from the body) Can be caused by: Uncontrolled diarrhea Vomiting Renal failure Heat stroke Water deprivation
DEHYDRATION Mechanism of development Total body water Deficit of water Shared amongst the plasma, IC and interstitial compartments Tissue perfusion is reduced +/- Hypovolemic shock
DEHYDRATION Gross Findings Skin pulled away from body tents Eyes are shrunken Mucous membranes and subcutaneous tissue are dry/sticky (tacky)