Circulatory Disturbances 1: Introduction and Edemapeople.upei.ca/smartinson/Circ_1-Edema-16_SAM_final.pdf · EDEMA Learning Objectives •Define edema •Recognize and be able to

Circulatory Disturbances 1: Introduction and Edema

Shannon Martinson, January 2016 http://people.upei.ca/smartinson/ VPM 152 General Pathology

INTRODUCTION – NORMAL CIRCULATORY SYSTEM

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!

Important concepts

Components of the Circulatory System


Pump Distribution system

Collection system

Microcirculation system

Artery

Vein

Components of the Circulatory System


• All components of the circulatory system are lined by a single layer of endothelium • Effect:

– Fluid balance – Hemostasis – Inflammation / immunity – Angiogenesis / healing


Endothelial cells

Image: Zachary and McGavin PBVD


Microcirculation

• ↑ 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


Capillaries

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


Mechanisms for transport of substance across capillary walls

Gas Lipid soluble molecules

Water, Ions, Glucose, Amino acids

Capillary wall is semipermeable membrane


Mechanisms for transport of substance across capillary walls

Transcytosis • With some endothelial cells, fluids / macromolecules can be

transported across a cell by vesicles


Regional differences in capillary lining

Continuous capillary

• Muscle • Brain • Skin • Bone • Lung




Fenestrated capillary

• Intestinal villi • Kidney

interstitium • Choroid plexus • Glomeruli




Discontinuous capillary (sinusoids)

• Hepatic and splenic sinuses



Fluid distribution and Homeostasis

Total Body Water

Extracellular Fluid

Plasma Interstitial

fluid Transcellular

fluid

Intracellular fluid

5% 15% 5%

40% 25%

65%


• is the space between microcirculation and the cells Interstitium

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

• Structural molecules: • Collagen, reticulin & elastin fibers

• Ground substance: • Adhesive glycoproteins (eg fibronectin, laminin) • Absorptive glycosaminoglycans / proteoglycans

Extracellular Matrix



• Structural molecules: • Collagen, reticulin & elastin fibers

• Ground substance: • Adhesive glycoproteins (eg fibronectin, laminin) • Absorptive glycosaminoglycans / proteoglycans

Extracellular Matrix

• Distribution of fluids, nutrients & wastes between blood→interstitium → cells controlled by physical structures, pressures and ion concentration gradients


Distribution of Fluids

• Capillaries (endothelial cells + basal lamina): • Allow the free passage of H2O & 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 in the vascular system + interstitial osmotic pressure moves fluid out of the vascular system.



Plasma hydrostatic pressure

Tissue colloidal osmotic pressure

Starlings Equation

• The osmotic pressure of the plasma proteins (+ tissue hydrostatic pressure) contains the fluid within the vascular system.





Plasma colloidal osmotic pressure

Tissue hydrostatic pressure

Starlings Equation



* *

Starlings Equation





Plasma colloidal osmotic pressure

Tissue hydrostatic pressure

Excess fluid Lymphatic drainage

Starlings Equation → Net movement of fluid out of the capillaries

CIRCULATORY DISTURBANCES

Edema Congestion and Hyperemia

Hemorrhage Thrombosis and Embolism

Infarction Shock

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

Gross Appearance of Edema • Organs wet (± gelatinous) and heavy

• Organs swollen and fluid may weep from cut surface

• May be yellow

EDEMA

• Abnormal (excess) accumulation of fluid in interstitial tissue spaces or 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


EDEMA


hronic local passive hyperemia

1) ↑Intravascular hydrostatic pressure

2) ↓Plasma colloidal osmotic pressure

3) ↓ Lymphatic drainage

4) ↑Vascular permeability

Edema – 4 Pathophysiological Mechanisms of Development

EDEMA

Due to impaired venous blood flow

• Generalized edema– eg heart failure

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

NORMAL

1. Increased intravascular hydrostatic pressure

EDEMA - Pathophysiological Mechanisms of Development

Due to hypoproteinemia

• Proteins not absorbed

• Starvation

• Malabsorption

• Proteins not produced

• Liver disease

• Proteins lost**

• Kidney (glomerular) disease

• Intestinal damage

• Causes generalized edema

NORMAL

2. Decreased plasma colloidal osmotic pressure


Plasma colloidal osmotic pressure is exerted mostly by plasma protein

Due to lymphatic obstruction / damage

• Surgery / trauma (fibrosis)

• Neoplasm (tumour) or mass

• Inflammation (lymphangitis)

• Typically localized

NORMAL

3. Decreased lymphatic drainage


1) ↑Blood hydrostatic 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 109 / L


Increased permeability

• Mostly due to inflammatory / immune reactions release of inflammatory mediators

• “inflammatory edema”

• Endothelium can be directly damaged by specific agents (eg viruses, toxins)

NORMAL

4. Increased vascular permeability/ Endothelial damage




• Fluid Characteristics: • Protein rich • Exudate:

• High protein content > 30g/L • High specific gravity > 1.025 • High nucleated cells > 7 x 109 / L



1) ↑Blood hydrostatic pressure

• Generalized edema

• Localized edema


• Generalized edema

3) ↓Lymphatic drainage

• Localized edema

4) ↑Vascular permeability

• Localized edema

LOCALIZED VS GENERALIZED EDEMA

Mechanisms of Development

Local impaired venous drainage

Local lymphatic blockage

Local inflammation

Local Edema


Generalized Edema

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”)

Mechanisms of Development

Increased hydrostatic pressure • Heart failure

Decreased colloidal osmotic pressure • Hypoproteinemia


Generalized Edema


TERMINOLOGY OF EDEMA

• When pressure is applied to an area of edema and a depression or dent results Pitting edema

• Severe and generalized edema with profound subcutaneous tissue swelling Anasarca


• Non-inflammatory fluid (transudate) in the thoracic cavity Hydrothorax


• Non-inflammatory fluid (transudate) in the pericardial sac Hydropericardium


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

Hydroperitoneum

= Ascites


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

• Accumulation of fluid in interstitium and alveoli of the lungs

• Common cause of death in many disease processes

Pulmonary edema

Normal lung Pulmonary edema

PULMONARY EDEMA

• Increased hydrostatic pressure

• Especially left sided heart failure

• Non-inflammatory edema into the alveolar spaces

1. Circulatory failure

Mechanisms of development

PULMONARY EDEMA

• Usually with peracute inflammation (inflammatory edema) or toxins

• If increased vascular permeability is substantial and widespread → death (ARDS – acute respiratory distress syndrome)

2. Damage to the pulmonary capillary endothelium

Mechanisms of development

1. • Fluid accumulates in the

interstitium

2. • Fluid moves through the basement

membranes into the alveoli

3. • Fluid drains via lymphatics

4. • +/- pleural fibrosis if chronic

Alveolar space

PULMONARY EDEMA

Dynamics of pulmonary edema

PULMONARY EDEMA

• Lungs are heavy and wet

• Interlobular septa are distended with fluid

• Froth in airways on cut surface

Gross appearance:

PULMONARY EDEMA

• Lungs are heavy and wet

• Interlobular septa are distended with fluid

• Froth in airways on cut surface

Gross appearance:

Normal lung

PULMONARY EDEMA

• Fluid in interstitium / alveolar spaces

• Dilated pleural / septal lymphatics

• Often pink

Histologic appearance:

• Chronicity → fibrosis of pleura & alveolar septa

• Most commonly seen with cardiac failure and accompanying pulmonary congestion

Chronic pulmonary edema

PULMONARY EDEMA

CEREBRAL EDEMA

• Trauma to brain

• Obstruction of venous outflow

• Intracranial infections

Causes

• Brain is heavier than normal

• Sulci are narrow

• Gyri are swollen and flattened

Gross appearance

• Herniation of the cerebellum through the foramen magnum

Cerebellar coning

CEREBRAL EDEMA

• Herniation of caudal cerebral cortex beneath the tentorium cerebelli

Cerebral herniation

Normal

Normal

CEREBRAL EDEMA

Normal

CEREBRAL EDEMA

• Expansion of the Virchow-Robin spaces

Histologic appearance

DEHYDRATION

• Deficiency of water (imbalance between uptake and loss) Dehydration

Can be caused by:

Uncontrolled diarrhea

Vomiting

Renal failure

Diabetes

Heat stroke

Water deprivation

DEHYDRATION

+/- Hypovolemic shock

Tissue perfusion is reduced

Deficit of water

Shared among plasma, intracellular and interstitial fluid compartments

↓Total body water

Mechanism of development

• Skin pulled away from body “tents”

• Eyes are shrunken

• Mucous membranes and subcutaneous tissue are dry/sticky (at necropsy)

Gross Findings

DEHYDRATION

Questions?

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

Documents

Circulatory Disturbances 1: Introduction and Edemapeople.upei.ca/smartinson/Circ_1-Edema-16_SAM_final.pdf · EDEMA Learning Objectives •Define edema •Recognize and be able to