Circulation and Fluid Balance (In Progress)

What are the functions of the circulatory system?

-Provide nutrients

-Remove wastes

-Maintain homeostasis

-Coordinate functions of diverse tissues

What are the components of circulation?

-Blood

-Heart

-Blood vessels

-Lymphatic vessels

What are the components of microcirculation?

-Blood vessels

-Lymphatic vessels

-Extracellular matrix (interstitium)

What blood vessels are part of microcirculation

-Terminal arterioles

-Capillaries

-Post capillary venules

What makes up terminal arterioles?

Endothelium, basement membrane, muscle

What makes up capillaries?

Endothelium, basement membrane

What makes up postcapillary venules?

Endothelium, basement membrane, muscle

What is the major resistance vessel of the arterial system?

Terminal arterioles

What regulates the flow of blood into a capillary bed?

Terminal arterioles

What happens to pressure as blood flows through the arteriole into the capillary?

It falls dramatically

What are the most numerous of all vessels?

Capillaries

Blood is directed into a capillary based on what?

Tissue needs

What provides capillaries with a semipermeable nature?

Interendothelial pores at the junctions between endothelial cells

Why are capillaries semipermeable?

Permeability is important to facilitate diffusion of materials between the intravascular and extravascular spaces

What are the functions of postcapillary venules?

-Post-capillary venules collect blood from a capillary bed to begin the venous return to the heart

-This is an important site of cellular events associated with inflammation

Where do blind-ended lymphatic vessels originate?

In association with the microcirculation

What are important participants in fluid balance at the microcirculatory level?

Lymphatics

What is the interstitium?

The space between cells and the microcirculation

What is the interstitium composed of?

The ECM

What is fluid homeostasis?

Fluid (water) is in a constant flux between compartments of the microcirculatory environment

Interactions in fluid homeostasis can occur between what?

-Cells and interstitium

-Interstitium and blood vessels

-Interstitium and lymphatic vessels

What is fluid distribution between compartments controlled by?

Physical barriers, and differences in pressure and concentration of substances within the fluid

What percent of body weight is total body water?

60%

What percent of body weight is extracellular water?

20%

What percent of body weight is plasma?

4-5%

What percent of body weight is interstitium?

16%

What percent of body weight is intracellular water?

40%

What is the barrier that separates intravascular and interstitial compartments?

Blood vessel wall (capillary)

What is the capillary wall?

A semi-permeable membrane that allows selective movement of fluid and molecules

What substances move through the endothelial cell of a capillary wall?

Lipid soluble substances

What substances move through inter-endothelial pores of a capillary wall?

Water and water soluble substances

What separates the lymphatic and interstitial compartments?

The lymph vessel wall

Is the lymph vessel wall or capillary wall more permeable?

Lymph vessel wall (inter-endothelial gaps are large)

Water moves freely between lymphatic vessel lumens and interstitium based on what?

Pressure gradients

What controls intravascular/interstitial fluid distribution?

-Anatomic integrity of the circulation

-Osmotic pressure (plasma, interstitium)

-Hydrostatic pressure (plasma, interstitium)

What are differences in hydrostatic pressure determined mainly by?

The volume of water in a compartment and any driving force acting on that volume (e.g. blood pressure)

What are differences in osmotic pressure determined mainly by?

Large proteins or protein-disaccharides:

-Small proteins and electrolytes account for most osmolality, but are equally distributed between fluid compartments

84% of plasma osmolality is due to what?

Sodium and chloride

Less than 1% of plasma osmolality is due to what?

Plasma proteins

What contributes to interstitial osmolality?

Protein-disaccharides

What is the major factor in driving water exchange between the plasma and interstitium?

Differences in intravascular hydrostatic pressure between arteriolar and venular ends of the microcirculation

What controls fluid distribution?

-Net filtration pressure (plasma/interstitium pressure differential at the arteriole, net flow (nutrients) into the interstitium)

-Net absoprtion pressure (plasma/interstitium pressure differential at the venule, net flow into the plasma)

-Lymphatic vessels pick up excess fluid

What is edema?

The increased accumulation of fluid in interstitial spaces or body cavities

What are the 4 mechanisms of edema?

-Decreased plasma osmotic pressure

-Increased plasma hydrostatic pressure

-Decreased lymphatic drainage

-Increased vascular permeability

What is a common underlying factor in decreased plasma osmotic pressure?

Hypoalbuminemia

What is the major plasma protein that contributes to intravascular osmotic pressure?

Albumin

What conditions can cause hypoalbuminemia?

-Starvation: Inadequate protein intake

-Liver disease: Decreased protein production

-Renal disease (nephrotic syndrome): Glomerular loss of albumin

-Gastrointestinal disease: malabsorption, parasitism

-Severe burns

Due to the systemic nature of hypoalbuminemia, edema tends to be what?

Generalized

What does increased plasma hydrostatic pressure create?

A net outflow of fluid from the vessel to the interstitium

What happens to the normal absorptive pressure at the venules when there is increased plasma hydrostatic pressure?

The normal absorptive pressure becomes a filtration pressure

High venular hydrostatic pressure prevents what?

Reentry of fluid from the interstitium

what conditions result in increased hydrostatic pressure?

-Increased blood flow (i.e. hyperemia):Acute inflammation

-Passive blood accumulation (i.e. congestion): Venous obstruction (thrombi, masses; inflammatory or neoplastic, organ torsions), Heart failure (flow backs up at heart)

Where does blood back up in right sided heart failure?

In the portal circulation (causes ascites)

What is the name for fluid in the abdomen?

Ascites

Where does blood back up in left sided heart failure?

In pulmonary circulation --> fluid accumulates in the alveoli of the lungs

What is fluid accumulation in the alveoli of the lung called?

Pulmonary edema

What can generalized edema associated with generalized heart failure cause?

Reduced circulating blood volume

What do ADH and aldosterone do during heart failure?

ADH and aldosterone stimulate water and sodium retention to contribute to hypervolemia and increased plasma hydrostatic pressure

Describe how decreased lymphatic drainage can cause edema

Any decrease in lymphatic flow prevents removal of the slight excess of fluid that normally persists in the interstitium during intravascular/interstitial fluid exchange

What conditions can cause decreased lymphatic drainage?

-Lymphatic obstruction

-Lymphatic anomalies

What can cause lymphatic obstruction?

-Compression from inflammatory or neoplastic masses

-Intralumenal obstruction by thrombi or emboli

What can cause lymphatic anomalies?

Congenital anasarca/lymphedema

Fluid maldistribution is almost always ______________ for acquired defects in drainage

Local

Congenital defects in lymphatics can be manifested by what?

Generalized edema

What does decreased structural integrity of a vessel allow for?

Water to move out of a vessel into the interstitium more freely

What conditions can cause increased vascular permeability?

-Inflammation

-Immunologic stimuli

-Direct endothelial injury

How can inflammation cause edema?

Endothelial contractions and cytoskeletal rearrangement results in expansion of inter-endothelial junctions and fluid movement to the interstitium

What inflammatory mediators are involved in the immediate transient response?

Histamine, bradykinin, leukotrines C4D4E4, platelet activating factor, substance P

What inflammatory mediators are involved in the delayed sustained response?

TNF, IL-1, gamma-IFN

How do immunologic stimuli cause increased vascular permeability?

Many of the same events that accompany inflammation are stimulated

What can cause direct endothelial injury?

Toxins, chemicals or infectious agents

When can you see more widespread fluid loss/edema?

In cases of systemic hypersensitivity

What is the gross morphology of edema?

Clear, gel-like fluid within tissue