circulatory disturbances 1: introduction and...

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

EDEMA

Circulatory Disturbances 1: Introduction and Edema

Shannon Martinson, January 2017

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

PumpDistribution

system Collection

system

Microcirculation system



Components of the Circulatory System

Endothelial cells

Image: Zachary PBVD 2017


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

• Endothelial cells affect:• Fluid balance• Hemostasis• Inflammation / immunity• Angiogenesis / healing

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 balanceImage: Mescher, Junqueira’s Basic Histology, 12 ed

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

GasLipid soluble molecules

Water, Ions, Glucose,Amino acids


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

transported across a cell by vesicles

Capillary wall is semipermeable membrane

Mechanisms for transport of substance across capillary walls


Fluid distribution and Homeostasis

Total Body Water

Extracellular Fluid

Plasma Interstitial

fluid

Intracellular fluid

5%15%

40%20%

60%


• The space between microcirculation and the cellsInterstitium

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


Extracellular Matrix


• Structural molecules:• Collagen, reticulin & elastin fibers

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

Image: Zachary PBVD 2017

• Distribution of fluids, nutrients & wastes between blood→

interstitium→ cells controlled by physical structures, pressure gradients 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



The osmotic pressure exerted by proteins is referred to as oncotic pressure

Hydrostatic pressure is the pressure exerted by a fluid in a confined space

• 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 and tissue hydrostatic pressure contains the fluid within the vascular system.



Plasma colloidal osmotic pressure

Tissue hydrostatic pressure

Starlings EquationDistribution of Fluids


Hydrostatic pressure drops along the length of the capillary bed!



Starlings Equation

Hydrostatic pressure drops along the length of the capillary bed!



Plasma colloidal osmotic pressure

Tissue hydrostatic pressure

Excess fluid Lymphatic drainage

Starlings Equation → Net movement of fluid out of the capillaries



Excess fluid is drained via lymphatics

CIRCULATORY DISTURBANCES

Edema

Hyperemia and congestion

Shock

Hemorrhage

Thrombosis and embolism

Infarction

Gross Appearance of Edema

• Organs wet (± gelatinous) and heavy

• Organs swollen and fluid may weep from cut surface

• Fluid present in the body cavities

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

EDEMA

EDEMA

Edema in the stomach wall

EDEMA

Edema in the stomach wall

Histologic Appearance of Edema

• Lightly staining eosinophilic fluid (if some protein content)

• Clear / no staining (if protein content low)

• Lymphatics usually dilated

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

• Generalized edema: eg Heart failure**

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

Due to impaired venous blood flow

NORMAL

1. Increased intravascular hydrostatic pressure

EDEMA - Pathophysiological Mechanisms of Development

• Proteins not produced

• Liver disease

• Proteins lost

• Kidney (glomerular) disease

• Intestinal damage

• Proteins not absorbed

• Starvation

• Malabsorption

• Causes generalized edema

Due to hypoproteinemia

NORMAL

2. Decreased plasma colloidal osmotic pressure

Plasma colloidal osmotic pressure is exerted mostly by plasma protein


• Surgery / trauma (fibrosis)

• Neoplasm (tumour) or mass

• Inflammation (lymphangitis)

• Typically localized

Due to lymphatic obstruction / damage

NORMAL

3. Decreased lymphatic drainage


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

• “inflammatory edema”

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

Increased permeability

NORMAL

4. Increased vascular permeability/ Endothelial damage


1) ↑Blood hydrostatic pressure

2) ↓Plasma colloidal osmotic pressure

3) Lymphatic obstruction

• Transudate:• Low protein content <30g/L• Low specific gravity <1.025• Few nucleated cells <1.5x 109 / L


4) ↑Vascular permeability

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

Fluid Characteristics:

Mechanisms of Development

Local impaired venous drainage

Local lymphatic blockage

Local inflammation

Localized Edema

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

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

TERMINOLOGY OF EDEMA

vet.uga.edu

http://vet.uga.edu/ivcvm/courses/VPAT5200/02_injury/amyloid/amy02d.html

• Severe and generalized edema with profound subcutaneous tissue swellingAnasarca


• Non-inflammatory fluid (transudate) in the thoracic cavityHydrothorax


• Non-inflammatory fluid (transudate) in the pericardial sacHydropericardium


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

Hydroperitoneum

= Ascites


Dependent upon:1. Extent: mild < moderate < marked / severe2. Location: skin < lung < brain3. Duration: acute vs chronic

• Increase in fibrous connective tissue after prolonged edema

CLINICAL SIGNIFICANCE OF EDEMA

• Accumulation of fluid in interstitium and alveoli of the lungs

• Common cause of death in many disease processesPulmonary edema

Normal lung Pulmonary edema

PULMONARY EDEMA

• Increased hydrostatic pressure: especially left sided heart failure

• Flooding of the alveolar spaces with transudate

1. Circulatory failure

Mechanisms of development

PULMONARY EDEMA

• Usually with acute 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

PULMONARY EDEMA

Mechanisms of development

• Lungs are heavy and wet

• Interlobular septa are distended with fluid

• Froth in airways on cut surface

Gross appearance:

PULMONARY EDEMA

PULMONARY EDEMA

• Lungs are heavy and wet

• Interlobular septa are distended with fluid

• Froth in airways on cut surface

Gross appearance:

Normal lung

• Fluid in interstitium / alveolar spaces

• Dilated pleural / septal lymphatics

• Often pink (proteinaceous)

Histologic appearance:

PULMONARY EDEMA

• Chronicity → fibrosis of pleura & alveolar septa

• Most commonly seen with cardiac failure and accompanying pulmonary congestion

Chronic pulmonary edema

PULMONARY EDEMA

• Trauma to brain

• Obstruction of venous outflow

• Intracranial inflammation

Causes

• Brain is heavier than normal

• Sulci are narrow

• Gyri are swollen and flattened

Gross appearance

CEREBRAL EDEMA

http://ocw.tufts.edu

• Herniation of the cerebellum through the foramen magnum

Cerebellar coning

CEREBRAL EDEMA

Zachary, PBVD, 2017

• Herniation of caudal cerebral cortex beneath the tentorium cerebelli

Cerebral herniation

Normal

CEREBRAL EDEMA

Zachary, PBVD, 2017

Normal

• Expansion of the Virchow-Robin spaces

Histologic appearance

CEREBRAL EDEMA

Zachary, PBVD, 2017

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

Can be caused by:

Uncontrolled diarrhea

Vomiting

Renal failure

Heat stroke

Water deprivation

DEHYDRATION

+/- Hypovolemic shock

Tissue perfusion is reduced

Shared amongst the plasma, IC and interstitial compartments

Deficit of water

↓Total body waterMechanism of development

DEHYDRATION

DEHYDRATION

• Skin pulled away from body “tents”

• Eyes are shrunken

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

Gross Findings

circulatory disturbances 1: introduction and...

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