General Pathology

Disturbances of Circulation Edema

(Web)

Paul Hanna Jan 2015

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)

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!

NORMAL 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 cross-sectional 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.

Components of the Circulatory System

Pump Distribution system Nutrient / waste Collection system Pump

exchange

[For Information only]

Artery

Vein

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.

[For Information only]

Microcirulation

Figure 11–13. (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.

[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

Capillaries [For Information only]

• all components of the circulatory system lined by a single layer of endothelium

• 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.

Endothelial cells [For Information only]

• 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

• in inflammation, endothelial cells contract, allowing larger molecules to escape

Mechanisms for Substance Transport Across Capillary Wall

Transcytosis

• some endothelium, fluids / macromolecules transported across a cell by vesicles

[For Information only]

Regional Differences in Capillary Lining

Jejunum

Liver

Muscle

(Discontinuous)

[For Information only]

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

• 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)

Interstitium [For Information only]

a) Structural molecules: collagen, reticulin & elastin fibers.

b) Ground substance: Adhesive glycoproteins (eg fibronectin, laminin)

Absorptive glycosaminoglycans / proteoglycans

Extracellular Matrix

C = collagen

E = elastic fibers

F = fibroblasts

Ground substance = appears as granular material in extracellular

space (artifact of gluteraldehyde –tannic acid fixation)

[For Information only]

Hyaluronan

Glycosaminoglycans & Proteoglycans

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 (SO3- & CO2

-) GAGs are the most

anionic molecule produced, bind cations (esp Na+), therefore

extremely hydrophilic.

[For Information only]

Proteoglycan Glycoprotein

Protein core

GAG chains

Extracellular Matrix

Web Fig. 3-23 (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.

[For Information only]

• H2O distribution between plasma & interstitium is primarily determined by hydrostatic

and osmotic pressure differences between the 2 compartments

• capillary (endotheial cell / BL): allows the free passage of H2O & ions

oppose the passage of plasma proteins

Movement of Fluids [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

* *

Starlings Equation

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.

[For Information only]

• Edema

• Congestion and Hyperemia

• Hemorrhage

• Hemostasis

• Thrombosis and Embolism

• Infarction

• Shock

CIRCULATORY DISTURBANCES

• 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. 2-10 (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).

Edema

Fig. 2-12 (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.

Normal

Edema

Histologic Appearance of Edema

• lightly staining eosinophilic fluid (if some protein content)

• clear / no staining (if protein content low)

• lymphatics usually dilated

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.

Edema

Mechanisms

Increased hydrostatic pressure (venous)

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!)

Edema

Normal

Causes of Impaired Venous Return

• Generalized – eg, right sided-heart failure.

• Localized – eg, tight bandage causing local obstruction of venous return.

Mechanisms

Decreased plasma colloidal osmotic (oncotic) pressure

Edema

Causes of Hypoproteinemia

Proteins not absorbed

• Starvation

• Malabsorption

Proteins not produced

• Liver disease

Proteins lost

• Glomerular disease

• Intestinal damage

Mechanisms

Lymphatic obstruction

Causes of Lymphatic Obstruction

Damage / obstruction of lymphatics

• Surgery / trauma (fibrosis)

• Neoplasm

• Inflammation (lymphangitis)

Edema

Fluid Characteristics

– “Protein poor” (“Non-inflammatory edema”)

– Transudate

• Low protein content < 30g/L

• Low specific gravity < 1.025

• Few nucleated cells <1.5 X109/L

Edema

Fluid Characteristics

-“Protein rich”

- Exudate

• High protein content > 30g/L

• Specific gravity > 1.025

• Total nucleated cells > 7 X109/L

Eema

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)

Edema

“inflammatory edema”

Bronchopneumonia with pleuritis

(pleuropneumonia) with abundant edema

(“inflammatory” edema, note fibrin clots)

Normal lung & thoracic cavity

Mechanisms

• local impaired venous drainage

• local lymphatic blockage

• local inflammation

Local Edema

note localized edema of the foot distal to constricting band

Generalized Edema

Fig. 10-12 (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.

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”)

Mechanisms

• hydrostatic psi (venous)

• colloid osmotic psi

Generalized Edema

note, hypoproteinemia due to gastrointestinal

parasitism is a common cause of dependant edema

in sheep; “bottle jaw” in this case.

Generalized Edema

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

Pitting Edema

• when pressure is applied to an area of subQ edema and a depression / dent results

Terminology

Anasarca

• severe and generalized edema with profound subcutaneous tissue swelling

Terminology

Hydrothorax

• non-inflammatory fluid (transudate) in the thoracic cavity

Terminology

Hydropericardium

• non-inflammatory fluid (transudate) in the pericardial sac

Terminology

Ascites (= hydroperitoneum)

• non-inflammatory fluid (transudate) in the peritoneal cavity

Terminology

Dependent upon:

• Extent - mild vs moderate vs marked / severe

• Location - skin vs lung or brain

• Duration - increase in fibrous connective tissue after prolonged edema

Clinical Significance of Edema

Fig. 9-40 (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.

• definition = accumulation of edema fluid in interstitium and alveoli of the lungs

• common cause of death in many disease processes

Pulmonary Edema

Mechanisms

Pulmonary Edema

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

Pulmonary Edema

Dynamics

Fluid accumulates in interstitium:

1. Fluid moves through BM and accumulates in alveoli

2. Lymphatics dilated (± fibrosis if chronic)

Alveolar

space

Gross

• lungs are heavy and wet

• froth in airways and on cut surface

• interlobular septa distended with fluid

Pulmonary Edema

Histopathology • fluid in interstitium / alveolar spaces

• dilated pleural / septal lymphatics

• often pink (inflamm. > non-inflamm.)

Pulmonary Edema

Normal lung

• chronicity fibrosis of pleura & alveolar septa

• most commonly seen with cardiac failure and accompanying pulmonary congestion

Chronic Pulmonary Edema

Masson trichrome staining highlights fibrous thickening (ie connective tissue

stains green) of alveolar interstitium as the result of chronic pulmonary edema

Cerebral edema, dog. Note asymmetry of the

cerebral hemispheres, since cerebral edema in

this case is predominately in the left hemisphere.

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 (Edema of the Brain)

Fig. 14-87 (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).

Cerebellar coning

• herniation of the cerebellum through

the foramen magnum

Cerebral Edema

Fig. 14-86 (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).

Cerebral herniation

• herniation of caudal cerebral cortex beneath the tentorium cerebelli

Normal

Normal

Tentorium cerebelli – portion of the dura mater that separates the

cerebellum from the inferior portion of the occipital lobes

Fig. 14-30 Edema. A, Vasogenic edema. The perivascular spaces are

wide as a result of fluid leakage through the blood-brain barrier

(arrows) (Fig. 14-29). 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.

Normal

Histo

• expansion of Virchow-Robin spaces

Cerebral Edema

Causes

• uncontrolled diarrhea

• vomiting

• renal failure

• diabetes

• heat-stroke

• water deprivation

Definition

• deficiency of water (imbalance between uptake and loss)

DEHYDRATION

Note deeply sunken eye in

this dehydrated animal

• when severe see hypovolemic shock (plasma water drawn into interstitium & cells)

• renal perfusion is reduced

Mechanism

• in total body water deficit of water shared among plasma--cells--interstitium

DEHYDRATION

Gross

• skin pulled away from body “tents”

• eyes are shrunken

• mucous membranes and subQ tissues (at necropsy) are dry / sticky

DEHYDRATION

Note skin along dorsal neck and

back region remains “tented” in in

this severely dehydrated dog