General Pathology. Disturbances of Circulation Edema. (Web)

Transcription

1 General Pathology Disturbances of Circulation Edema (Web) Paul Hanna Jan 2015

2 The health of cells and organs critically depends on an unbroken circulation to deliver oxygen and nutrients and to remove wastes The well-being of tissues requires normal fluid balance; abnormalities in vascular permeability or hemostasis can result in injury (Pathologic Basis of Disease)

3 NORMAL CIRCULATORY SYSTEM [For Information only] 1. Distribution of fluid is carefully controlled 2. Deviations from normal can have profound pathological effects 3. Normal function requires intact blood and lymph vessels 4. Endothelial cells are important!

4 Components of the Circulatory System [For Information only] Fig. 2-1 (McGavin)The vascular system. Blood travels from the left side of the heart to the right side of the heart via the systemic circulation, and from the right side of the heart to the left side via the pulmonary circulation. Blood flow rate and pressure in the systemic arterial circulation decrease in conjunction with increased total arterial cross-sectional area. In the venous systemic circulation, blood flow rate, but not pressure, increases in conjunction with decreased total venous crosssectional area. The flow, pressure, and cross-sectional area relationships are similar but reversed (i.e., veins deliver blood and arteries collect blood) in the pulmonary circulation. Pump Distribution system Nutrient / waste Collection system Pump exchange

5 [For Information only] Artery Figure 11 7 (Mescher). Walls of arteries, veins, and capillaries. Walls of both arteries and veins have a tunica intima, tunica media, and tunica externa (or adventitia), which correspond roughly to the heart s endocardium, myocardium and epicardium. An artery has a thicker tunica media and relatively narrow lumen. A vein has a larger lumen and its tunica externa is the thickest layer. The tunica intima of veins is often folded to form valves. Capillaries have only an endothelium, with no subendothelial layer or other tunics. Vein

6 Microcirulation [For Information only] Figure (Mescher) Structure of microvasculature. Microvasculature arises to meet nutritional needs of one organ or parts of one organ and consists of blood vessels of less than 0.5 mm diameter. Microvessels include arterioles and their smaller branches called metarterioles in which the layer of smooth muscle cells is dispersed as bands of cells that act as precapillary sphincters. The distal portion of the metarteriole, sometimes called a thoroughfare channel, lacks any smooth muscle cells. The wall of capillaries lacks smooth muscle cells altogether. The precapillary sphincters allow blood to enter the bed of capillaries in a pulsatile manner for maximally efficient exchange of nutrients, wastes, O2, and CO2 across the capillary wall. Capillaries and the metarteriole converge as postcapillary venules, the last component of the microvasculature. Blood enters microvasculature well oxygenated and leaves poorly oxygenated.

7 Capillaries [For Information only] enormous volume (1300 X cross-sectional area of aorta) but normally contain only ~5% of the blood site where nutrients & wastes are exchanged and are critical in fluid balance

8 Endothelial cells all components of the circulatory system lined by a single layer of endothelium [For Information only] effect: fluid balance hemostasis inflammation / immunity angiogenesis / healing Fig. 2-6 (McGavin) Structure and function of the endothelium. Endothelium is both a physical barrier between intravascular and extravascular spaces, and it is an important mediator of fluid distribution, hemostasis, inflammation, and healing.

9 Mechanisms for Substance Transport Across Capillary Wall capillary wall is semipermeable membrane [For Information only] 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 in inflammation, endothelial cells contract, allowing larger molecules to escape Transcytosis some endothelium, fluids / macromolecules transported across a cell by vesicles

10 Regional Differences in Capillary Lining [For Information only] Muscle Jejunum (Discontinuous) Liver

11 Fluid Distribution & Homeostasis [For Information only] TOTAL BODY WATER Intracellular fluid (40%) Plasma ( 5%) ECF Interstitial fluid (15%) Transcellular fluid ( 5%) 65% of Lean Body Weight

12 Interstitium [For Information only] is the space between microcirculation and the cells medium through which all metabolic products must pass between microcirculation and cells distribution of fluids, nutrients & wastes between blood-interstitium-cells controlled by physical structures, pressures and ion concentration gradients interstitium = ECM + fluid ECM properties: structural support adhesion absorption (hygroscopic)

13 Extracellular Matrix [For Information only] a) Structural molecules: collagen, reticulin & elastin fibers. b) Ground substance: Adhesive glycoproteins (eg fibronectin, laminin) Absorptive glycosaminoglycans / proteoglycans C = collagen E = elastic fibers F = fibroblasts Ground substance = appears as granular material in extracellular space (artifact of gluteraldehyde tannic acid fixation)

14 Glycosaminoglycans & Proteoglycans [For Information only] Glycosaminoglycans are unbranched polysaccharide chains composed of repeating disaccharide units. one of the sugars is always an amino sugar (N-acetylglucosamine or N-acetylgalactosamine); usually sulfated. second sugar is usually a uronic acid (glucuronic or iduronic); with carboxyl group. other than hyaluronic acid, GAG s are attached to a protein core forming a proteoglycan molecule. due to high negative charges (SO 3 - & CO 2- ) GAGs are the most anionic molecule produced, bind cations (esp Na + ), therefore extremely hydrophilic. Hyaluronan Proteoglycan Glycoprotein GAG chains Protein core

15 Extracellular Matrix [For Information only] Web Fig (Zachary & McGavin) Extracellular matrix (ECM). Main components of the extracellular matrix (ECM), including collagens, proteoglycans, and adhesive glycoproteins. Both epithelial and mesenchymal cells (e.g., fibroblasts) interact with ECM via integrins. Basement membranes and interstitial ECM have different architecture and general composition, although there is some overlap in their constituents. For the sake of simplification, many ECM components (e.g., elastin, fibrillin, hyaluronan, and syndecan) are not included.

16 Movement of Fluids [For Information only] capillary (endotheial cell / BL): allows the free passage of H 2 O & ions oppose the passage of plasma proteins H 2 O distribution between plasma & interstitium is primarily determined by hydrostatic and osmotic pressure differences between the 2 compartments

17 Starlings Equation [For Information only] hydrostatic pressure in the vascular system (+ interstitial osmotic pressure) moves fluid out of the vascular system the osmotic pressure of the plasma proteins (+ some tissue hydrostatic pressure) contains the fluid within the vascular system * * Factors influencing fluid transit across capillary walls. Capillary hydrostatic and osmotic forces are normally balanced so that there is no net loss or gain of fluid across the capillary bed. However, increased hydrostatic pressure (in the venule) or diminished plasma osmotic pressure will cause extravascular fluid to accumulate. Tissue lymphatics removes the small amount of excess volume, eventually returning it to the circulation via the thoracic duct; however, if the capacity for lymphatic drainage is exceeded, tissue edema results.

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19 CIRCULATORY DISTURBANCES Edema Congestion and Hyperemia Hemorrhage Hemostasis Thrombosis and Embolism Infarction Shock

20 Edema Definition abnormal (excess) accumulation 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 Fig (McGavin) Pulmonary edema, lung, pig. The lung failed to collapse and has a firm rubbery texture attributable to edema fluid in alveoli and the interstitium. Note the prominent interlobular septa caused by edema (arrowhead) and the frothy edema fluid exuding from the bronchus (arrow).

21 Edema Histologic Appearance of Edema lightly staining eosinophilic fluid (if some protein content) clear / no staining (if protein content low) lymphatics usually dilated Normal Fig (McGavin) Pulmonary edema, lung, rat. There is eosinophilic (pink staining) fluid distending the alveoli in the lower specimen. Histologically, edema is an amorphous, pale eosinophilic fluid, and the depth of the eosinophilia is proportional to its protein content. The fluid in this specimen has a high protein content. The upper specimen is normal rat lung. H&E stain.

22 Edema Gastric and intestinal edema, horse. On gross examination, note the marked submucosal edema of the intestine (top right) and stomach wall (bottom right). Histologically (above) the clear (protein poor) edema fluid has markedly expanded the submucosa.

23 Edema Mechanisms Increased hydrostatic pressure (venous) Normal Note, the increased hydrostatic pressure applies only to the venous side of the capillary. Hypertension (high blood pressure) on the arterial side doesn t extend down to the arteriole!) Causes of Impaired Venous Return Generalized eg, right sided-heart failure. Localized eg, tight bandage causing local obstruction of venous return.

24 Edema Mechanisms Decreased plasma colloidal osmotic (oncotic) pressure Causes of Hypoproteinemia Proteins not absorbed Starvation Malabsorption Proteins not produced Liver disease Proteins lost Glomerular disease Intestinal damage

25 Edema Mechanisms Lymphatic obstruction Causes of Lymphatic Obstruction Damage / obstruction of lymphatics Surgery / trauma (fibrosis) Neoplasm Inflammation (lymphangitis)

26 Edema Fluid Characteristics Protein poor ( Non-inflammatory edema ) Transudate Low protein content < 30g/L Low specific gravity < Few nucleated cells <1.5 X10 9 /L

27 Eema Edema Mechanisms Increased Vascular Permeability / Endothelial damage mostly due to inflammatory / immune reactions inflammatory edema endothelium can also be directly damaged by specific agents (eg viruses, toxins) Fluid Characteristics - Protein rich - Exudate High protein content > 30g/L Specific gravity > Total nucleated cells > 7 X10 9 /L

28 inflammatory edema Normal lung & thoracic cavity Bronchopneumonia with pleuritis (pleuropneumonia) with abundant edema ( inflammatory edema, note fibrin clots)

29 Local Edema Mechanisms local impaired venous drainage local lymphatic blockage local inflammation note localized edema of the foot distal to constricting band

30 Generalized Edema Mechanisms hydrostatic psi (venous) colloid osmotic psi Location often see ascites, hydrothorax & subcutaneous ( dependent ) edema - subcutis of ventral abdomen / thorax ( brisket edema ) - subcutis of the ventral cervical / mandibular region ( bottle jaw ) - subcutis of the limbs ( stocking up ) Fig (McGavin) Subcutaneous edema, high altitude disease with congestive heart failure ( brisket disease ), presternal, sternal, and caudal sternocephalic regions (brisket), cow. The extensive subcutaneous edema is the result of chronic congestive heart failure.

31 Generalized Edema note, hypoproteinemia due to gastrointestinal parasitism is a common cause of dependant edema in sheep; bottle jaw in this case.

32 Generalized Edema Subcutaneous edema, limbs, equine. This horse had generalized edema due to protein losing enteropathy

33 Terminology Pitting Edema when pressure is applied to an area of subq edema and a depression / dent results

34 Terminology Anasarca severe and generalized edema with profound subcutaneous tissue swelling

35 Terminology Hydrothorax non-inflammatory fluid (transudate) in the thoracic cavity

36 Terminology Hydropericardium non-inflammatory fluid (transudate) in the pericardial sac

37 Terminology Ascites (= hydroperitoneum) non-inflammatory fluid (transudate) in the peritoneal cavity

38 Clinical Significance of Edema Dependent upon: Extent - mild vs moderate vs marked / severe Location - skin vs lung or brain Duration - increase in fibrous connective tissue after prolonged edema

39 Pulmonary Edema definition = accumulation of edema fluid in interstitium and alveoli of the lungs common cause of death in many disease processes Fig (McGavin) Pulmonary edema, lungs, pig. A, The lungs are distended by edema fluid, which has resulted in rounded edges and edematous distention of the interlobular septa. B, The cut surface is wet and the interlobular septa are markedly distended with edema fluid. Lung lobules are also congested.

40 Pulmonary Edema Mechanisms Circulatory failure increased hydrostatic pressure (esp left-sided heart failure) non-inflammatory edema into alveolar spaces Damage to pulmonary capillary endothelium usually with peracute inflammation ( inflammatory edema ) or toxins if increase in vascular permeability is substantial & widespread death

41 Pulmonary Edema Dynamics Fluid accumulates in interstitium: 1. Fluid moves through BM and accumulates in alveoli 2. Lymphatics dilated (± fibrosis if chronic) Alveolar space

42 Pulmonary Edema Gross lungs are heavy and wet froth in airways and on cut surface interlobular septa distended with fluid

43 Pulmonary Edema Histopathology fluid in interstitium / alveolar spaces dilated pleural / septal lymphatics often pink (inflamm. > non-inflamm.) Normal lung

44 Chronic Pulmonary Edema chronicity fibrosis of pleura & alveolar septa most commonly seen with cardiac failure and accompanying pulmonary congestion Masson trichrome staining highlights fibrous thickening (ie connective tissue stains green) of alveolar interstitium as the result of chronic pulmonary edema

45 Cerebral Edema (Edema of the Brain) Causes trauma to head obstruction of venous outflow intracranial infections Gross brain is heavier than normal sulci are narrow gyri are swollen & flattened Cerebral edema, dog. Note asymmetry of the cerebral hemispheres, since cerebral edema in this case is predominately in the left hemisphere.

46 Cerebral Edema Cerebellar coning herniation of the cerebellum through the foramen magnum Fig (McGavin) Coning of the cerebellar vermis, brain, cat. A, Sagittal section. Coning of the cerebellum. The caudal cerebellar vermis has been displaced caudally through the foramen magnum, note the notch on the dorsal surface (arrow). This result has compressed the medulla oblongata (MO), which can cause death from compression of the respiratory center. Note the elevation of the corpus callosum (CC) and focal compression of the rostral cerebellar vermis by the tectum (quadrigeminal plate) (QP).

47 Cerebral herniation herniation of caudal cerebral cortex beneath the tentorium cerebelli Tentorium cerebelli portion of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes Normal Normal Fig (McGavin) Gyral herniation, parahippocampal gyri, brain, transverse section, caudal face, at level of the rostral colliculi and crus cerebri, horse. The caudal displacement of the parahippocampal gyri (arrows; note bulging beneath the tentorium cerebelli dura matter removed) was caused by a sudden swelling of the brain (increase in intracranial pressure) from severe cerebral blunt force trauma to the head. The other cerebral gyri are swollen and flattened and sulci are indistinct (cerebral edema).

48 Cerebral Edema Histo expansion of Virchow-Robin spaces Normal Fig Edema. A, Vasogenic edema. The perivascular spaces are wide as a result of fluid leakage through the blood-brain barrier (arrows) (Fig ). A similar change can be seen around neurons. These fluid-filled spaces are often very difficult to differentiate from artifactual spaces caused by shrinkage from fixation and dehydration in the preparation of the paraffin-embedded sections. H&E stain.

49 DEHYDRATION Definition deficiency of water (imbalance between uptake and loss) Causes uncontrolled diarrhea vomiting renal failure diabetes heat-stroke water deprivation Note deeply sunken eye in this dehydrated animal

50 DEHYDRATION Mechanism in total body water deficit of water shared among plasma--cells--interstitium renal perfusion is reduced when severe see hypovolemic shock (plasma water drawn into interstitium & cells)

51 DEHYDRATION Gross skin pulled away from body tents eyes are shrunken mucous membranes and subq tissues (at necropsy) are dry / sticky Note skin along dorsal neck and back region remains tented in in this severely dehydrated dog

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