Circulatory Disturbances 1: Introduction and Edema

Transcription

1 Circulatory Disturbances 1: Introduction and Edema Shannon Martinson, January VPM 152 General Pathology

2 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!

3 INTRODUCTION NORMAL CIRCULATORY SYSTEM Components of the Circulatory System Collection system Pump Distribution system Microcirculation system

4 INTRODUCTION NORMAL CIRCULATORY SYSTEM Components of the Circulatory System Artery Vein

5 INTRODUCTION NORMAL CIRCULATORY SYSTEM Endothelial cells All components of the circulatory system are lined by a single layer of endothelium Effect: Fluid balance Hemostasis Inflammation / immunity Angiogenesis / healing Image: Zachary and McGavin PBVD

6 INTRODUCTION NORMAL CIRCULATORY SYSTEM Microcirculation

7 INTRODUCTION NORMAL CIRCULATORY SYSTEM Capillaries volume: 1300 x cross-sectional area of aorta Normally contain only ~5% of the blood Site where nutrients & wastes are exchanged Critical site for fluid balance

8 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

9 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

10 INTRODUCTION NORMAL CIRCULATORY SYSTEM Regional differences in capillary lining Continuous capillary Muscle Brain Skin Bone Lung Image: Zachary and McGavin PBVD

11 INTRODUCTION NORMAL CIRCULATORY SYSTEM Regional differences in capillary lining Fenestrated capillary Intestinal villi Kidney interstitium Choroid plexus Glomeruli Image: Zachary and McGavin PBVD

12 INTRODUCTION NORMAL CIRCULATORY SYSTEM Regional differences in capillary lining Discontinuous capillary (sinusoids) Hepatic and splenic sinuses Image: Zachary and McGavin PBVD

13 INTRODUCTION NORMAL CIRCULATORY SYSTEM Fluid distribution and Homeostasis Total Body Water 65% 25% 40% Extracellular Fluid Intracellular fluid Plasma Interstitial fluid Transcellular fluid 5% 15% 5%

14 INTRODUCTION NORMAL CIRCULATORY SYSTEM Interstitium is 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

15 INTRODUCTION NORMAL CIRCULATORY SYSTEM Extracellular Matrix Structural molecules: Collagen, reticulin & elastin fibers Ground substance: Adhesive glycoproteins (eg fibronectin, laminin) Absorptive glycosaminoglycans / proteoglycans

16 INTRODUCTION NORMAL CIRCULATORY SYSTEM Extracellular Matrix Structural molecules: Collagen, reticulin & elastin fibers Ground substance: Adhesive glycoproteins (eg fibronectin, laminin) Absorptive glycosaminoglycans / proteoglycans

17 INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Distribution of fluids, nutrients & wastes between blood interstitium cells controlled by physical structures, pressures and ion concentration gradients

18 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

19 INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Starlings Equation Hydrostatic pressure in the vascular system + interstitial osmotic pressure moves fluid out of the vascular system. Plasma hydrostatic pressure Tissue colloidal osmotic pressure

20 INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Starlings Equation The osmotic pressure of the plasma proteins (+ tissue hydrostatic pressure) contains the fluid within the vascular system. Plasma hydrostatic pressure Plasma colloidal osmotic pressure Tissue colloidal osmotic pressure Tissue hydrostatic pressure

21 INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Starlings Equation * *

22 INTRODUCTION NORMAL CIRCULATORY SYSTEM Distribution of Fluids Starlings Equation Net movement of fluid out of the capillaries Plasma hydrostatic pressure Plasma colloidal osmotic pressure Tissue colloidal osmotic pressure Tissue hydrostatic pressure Excess fluid Lymphatic drainage

23 CIRCULATORY DISTURBANCES Edema Hemorrhage Congestion and Hyperemia Thrombosis and Embolism Infarction Shock

24 EDEMA Learning Objectives Define edema Recognize and be able to describe the gross and microscopic appearance of edema Know the four 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

25 EDEMA EDEMA Abnormal (excess) accumulation of fluid in interstitial tissue spaces or body cavities Gross Appearance of Edema Organs wet (± gelatinous) and heavy Organs swollen and fluid may weep from cut surface May be yellow Image: Zachary and McGavin PBVD

26 Image: Zachary and McGavin PBVD EDEMA Histologic Appearance of Edema Lightly staining eosinophilic fluid (if some protein content) Clear / no staining (if protein content low) Lymphatics usually dilated

27 Image: Zachary and McGavin PBVD EDEMA

28 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

29 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

30 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 absorbed Starvation Malabsorption Proteins not produced Liver disease Proteins lost** Kidney (glomerular) disease Intestinal damage Causes generalized edema

31 EDEMA - Pathophysiological Mechanisms of Development 3. Decreased lymphatic drainage Due to lymphatic obstruction / damage Surgery / trauma (fibrosis) Neoplasm (tumour) or mass Inflammation (lymphangitis) Typically localized NORMAL

32 EDEMA - Pathophysiological Mechanisms of Development 1) Blood hydrostatic pressure 2) Plasma colloidal osmotic pressure 3) Lymphatic obstruction Fluid Characteristics: Protein poor (= non-inflammatory edema) Transudate: Low protein content <30g/L Low specific gravity <1.025 Few nucleated cells <1.5x 10 9 / L

33 EDEMA - Pathophysiological Mechanisms of Development 4. Increased vascular permeability/ Endothelial damage Increased permeability NORMAL Mostly due to inflammatory / immune reactions release of inflammatory mediators inflammatory edema Endothelium can be directly damaged by specific agents (eg viruses, toxins)

34 EDEMA - Pathophysiological Mechanisms of Development 4. Increased vascular permeability/ Endothelial damage Fluid Characteristics: Protein rich Exudate: High protein content > 30g/L High specific gravity > High nucleated cells > 7 x 10 9 / L

35 EDEMA - Pathophysiological Mechanisms of Development 4. Increased vascular permeability/ Endothelial damage

36 LOCALIZED VS GENERALIZED EDEMA 1) Blood hydrostatic pressure Generalized edema Localized edema 2) Plasma colloidal osmotic pressure Generalized edema 3) Lymphatic drainage Localized edema 4) Vascular permeability Localized edema

37 LOCALIZED VS GENERALIZED EDEMA Local Edema Mechanisms of Development Local impaired venous drainage Local lymphatic blockage Local inflammation

38 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 )

39 LOCALIZED VS GENERALIZED EDEMA Generalized Edema

40 TERMINOLOGY OF EDEMA Pitting edema When pressure is applied to an area of edema and a depression or dent results

41 TERMINOLOGY OF EDEMA Anasarca Severe and generalized edema with profound subcutaneous tissue swelling

42 TERMINOLOGY OF EDEMA Hydrothorax Non-inflammatory fluid (transudate) in the thoracic cavity

43 TERMINOLOGY OF EDEMA Hydropericardium Non-inflammatory fluid (transudate) in the pericardial sac

44 TERMINOLOGY OF EDEMA Hydroperitoneum = Ascites non-inflammatory fluid (transudate) in the peritoneal cavity

45 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

46 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

47 Mechanisms of development 1. Circulatory failure PULMONARY EDEMA Increased hydrostatic pressure Especially left sided heart failure Non-inflammatory edema into the alveolar spaces

48 Mechanisms of development PULMONARY EDEMA 2. Damage to the pulmonary capillary endothelium Usually with peracute inflammation (inflammatory edema) or toxins If increased vascular permeability is substantial and widespread death (ARDS acute respiratory distress syndrome)

49 Dynamics of pulmonary edema PULMONARY EDEMA 1. Fluid accumulates in the interstitium Fluid moves through the basement membranes into the alveoli Fluid drains via lymphatics Alveolar space 4. +/- pleural fibrosis if chronic

50 PULMONARY EDEMA Gross appearance: Lungs are heavy and wet Interlobular septa are distended with fluid Froth in airways on cut surface

51 PULMONARY EDEMA Gross appearance: Lungs are heavy and wet Interlobular septa are distended with fluid Froth in airways on cut surface

52 Histologic appearance: Fluid in interstitium / alveolar spaces Dilated pleural / septal lymphatics Often pink PULMONARY EDEMA Normal lung

53 Chronic pulmonary edema PULMONARY EDEMA Chronicity fibrosis of pleura & alveolar septa Most commonly seen with cardiac failure and accompanying pulmonary congestion

54 CEREBRAL EDEMA Causes Trauma to brain Obstruction of venous outflow Intracranial infections Gross appearance Brain is heavier than normal Sulci are narrow Gyri are swollen and flattened

55 CEREBRAL EDEMA Cerebellar coning Herniation of the cerebellum through the foramen magnum

56 CEREBRAL EDEMA Cerebral herniation Herniation of caudal cerebral cortex beneath the tentorium cerebelli Normal Normal

57 Histologic appearance CEREBRAL EDEMA Expansion of the Virchow-Robin spaces Normal

58 DEHYDRATION Dehydration Deficiency of water (imbalance between uptake and loss) Can be caused by: Uncontrolled diarrhea Vomiting Renal failure Diabetes Heat stroke Water deprivation

59 Mechanism of development DEHYDRATION Total body water Deficit of water Shared among plasma, intracellular and interstitial fluid compartments Tissue perfusion is reduced +/- Hypovolemic shock

60 DEHYDRATION Gross Findings Skin pulled away from body tents Eyes are shrunken Mucous membranes and subcutaneous tissue are dry/sticky (at necropsy)

61 A big thanks to Dr Hanna for providing me with material for these lectures! Questions?