Gen Path Lectures 13 and 14: Vascular Disorders

Capillaries

What is the most numerous vessel in the circulatory system?

5%

What percentage of the total blood volume do capillaries contain?

65%

What percentage of the total blood volume do veins contain?

Interstitium

1. Exchange of fluid, nutrients, and waste products between blood and tissue takes place here

2. Composed of extracellular matrix or collagen

Oxygen, CO2, non-charged fatty acids

Which substances can move freely (dependent on pressure and concentration gradient)?

Charged particles

Which substances may require pumps, receptors, and ATP to get across the plasma membrane?

Edema

Forms when there is an imbalance in fluid distribution between intravascular and interstitial compartments

Increased microvascular permeability, increased intravascular hydrostatic pressure, decreased intravascular oncotic pressure, decreased lymphatic drainage

Four mechanisms of edema

Inflammation

Common cause of increased vascular permeability

Increased vascular permeability

1. Inflammation is a common cause

   1. Mediators cause vasodilation and increased vascular permeability

      1. Histamine

      2. Substance P

   2. Fluid accumulation is an exudate

      1. High protein, high cells

Increased intravascular hydrostatic pressure

Increased blood volume either from an active or passive increase in blood flow

Hyperemia

1. Active increase in blood flow

2. Tissue will appear more red due to the increased blood flow

Physiologic hyperemia

Happens after exercise, blushing, or to the GI tract after a meal

Pathologic hyperemia

Happens during inflammation and neovascularization

Congestion

1. Passive accumulation of blood

2. Can be local or generalized

Local, generalized, hypostatic, liver mortis

Types of congestion

Hypostatic congestion

Pooling of blood in dependent regions shortly before death

Liver mortis

Gravity-dependent pooling of blood in tissues after death

Right-sided cardiac disease

1. Liver affected first

2. ___ ventricular insufficiency leads to increased venous blood pressure and eventually leads to congestion of the central veins

3. Eventually, fluid accumulates in cavities

4. Appearance of congested tissue

   1. Dark red, purple, or bluish

Left-sided cardiac disease

1. Lungs affected first

2. ___ ventricular insufficiency leads to increased pulmonary venous pressure and congestion of pulmonary veins and capillaries, which results in pulmonary edema

Hypoalbuminemia, hypoproteinemia

What does decreased oncotic pressure lead to?

Hemorrhage, GI loss, renal loss, decreased production by the liver

Causes of hypoalbuminemia

Decreased lymphatic drainage

Mass or dilation of lymphatics resulting in obstructed or impaired flow of lymphatic fluid

Hemostasis

Arrest in bleeding

Blood loss, thrombus formation

Disruption of hemostasis can result in ___ if hemostasis is hypofunctional or ___ if hemostasis is hyperfunctional.

Endothelium, platelets, coagulation cascade (secondary hemostasis), fibrinolysis

Main components of hemostasis

Hemorrhage

Results from abnormal integrity of one or more of the major factors that influence hemostasis (platelets, coagulation cascade, endothelium)

Volume, rate, and location of bleeding

What does the clinical significance of hemorrhage depend on?

Size of vessel

What does the level of hemorrhage depend on?

Petechia, ecchymoses, bruises

Clinical signs of platelet disorders

Thrombocytopenia, thrombocytopathy, vasculitis

Three causes of petechia

Thrombocytopenia

Low blood platelet count

Decreased production, increased destruction, increased use

Thrombocytopathy

Normal number of blood platelets; just don’t work well

E.g. Glanzmann’s thromboasthenia: deficient of defective GPIIb and GPIIIa

• Great Pyrenees, otterhound, horses, etc.

Petechiae

Small, flat 1-2 mm hemorrhages

Ecchymosis

Slightly larger (>3 mm) hemorrhages

Suffusive

Coalescing areas of ecchymotic hemorrhages

Epistaxis (nosebleeds), GI bleeding

What can mucosal bleeding cause?

Defects in primary hemostasis

Often present with small bleeds in skin or mucosal membranes

• Petechiae, ecchymosis, suffusive

Defects in secondary hemostasis

1. Encompasses most coagulation factor defects

2. Presents with larger bleeds

3. Bleeding into body cavities

   1. Hemothorax

   2. Hemoabdomen

   3. Hemopericardium

4. Bleeding into joint spaces

   1. Hemoarthrosis

Hematoma

Localized collection of usually clotted blood found in the tissue space (extravascular)

Hematuria

Blood in urine

Hematemesis

Vomiting blood

Hematochezia

Fresh blood in feces

Melena

Black, tarry, digested blood in feces

Blood clot

Semisolid mass/coagulum of blood, either in or out of the body

Thrombus

Blood clot inside a blood vessel that disrupts blood flow to a tissue, often resulting in ischemic necrosis and damage or death of the tissue

Aggregate of platelets, fibrin, and other components of blood formed on a vascular wall

Physiologic thrombus

Clot that forms as part of the hemostatic process

Pathologic/inappropriate thrombus

1. Can form in a vessel or on the heart wall as a result of one or all of the following three things:

   1. Abnormal blood flow

   2. Hypercoagulability

   3. Endothelial injury

Parts of Virchow triad

Endothelial injury, hypercoagulability, abnormal blood flow

Arterial thrombi

1. Usually form secondary to endothelial damage

   1. These are usually pale and consist of platelets and fibrin

Venous thrombi

1. More likely to form in areas of stasis or congestion

   1. Therefore, these are often red (due to the stasis, there is time for RBCs to accumulate)

Mural thrombi

Type of thrombi

Attached to the endocardium (the entire cardiac ventricle or atrium)

Vegetative thrombi

Septic thrombi on the heart valves that have a “cauliflower” appearance

Location, size, rate of development, ability to obstruct blood flow and cause ischemia

What is the significance of a thrombus determined by?

Propagation, embolization, dissolution, organization and recanalization

Fates of thrombi

Propagation

A fate of thrombi

Thrombi can continue to grow and add on more platelets and fibrin

Embolization

A fate of thrombi

Chunks break off and travel

Dissolution

A fate of thrombi

Fibrinolysis kicks in, and major shrinkage occurs

Embolus

1.  Detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site where it raises havoc

   1. Majority are dislodged from thrombi

   2. Others come from fat, atherosclerotic debris, tumor, gas bubble (often secondary to surgery), bone marrow, etc.

Pulmonary emboli

Most common type of emboli

Saddle thrombus

Embolus that has broken off a left arterial thrombus that has formed secondarily to hypertrophic cardiomyopathy

Shock

Tissue perfusion is impaired due to decreased cardiac output or reduced circulating blood volume (cardiac collapse)

Loss of blood volume, decreased cardiac output, inappropriate vascular resistance

Causes of shock

Cardiogenic, hypovolemic, blood maldistribution

Types of shock

Cardiogenic shock

1. Failure of the heart to adequately pump blood (decreased cardiac output)

   1. Cardiomyopathy (heart failure)

   2. Myocardial infarction (heart attack)

      1. Obstruction of blood flow from the heart (PTE)

Hypovolemic shock

1. Decreased circulating blood volume from:

   1. Blood loss (hemorrhage)

   2. Fluid loss (dehydration)

2. Results: Vasoconstriction to get blood to critical tissues

Blood maldistribution

1. Decreased peripheral vascular resistance and pooling of blood in peripheral tissues

   1. Neural or cytokine induced vasodilation

Anaphylactic shock

1. Type I hypersensitivity response

   1. Massive mast cell degeneration releasing histamine and other vasoactive mediators

      1. Vasodilation

      2. Vascular permeability

Neurogenic shock

1. Usually caused by trauma to CNS

2. Autonomic discharges that result in peripheral vasodilation

Septic shock

1. Components of bacteria cause the release of excessive amounts of vascular and inflammation mediators

   1. Most common is endotoxin, LPS complex from gram-negative bacteria

Stages of shock

Non-progressive, progressive, irreversible

Non-progressive

Stage of shock

Compensatory responses to decreased pressure

Progressive

Stage of shock

1. Disease too severe to be controlled by compensatory mechanisms

2. Blood pools; tissues are hypoperfused, resulting in progressive cell injury

   1. Inefficient production of ATP

   2. Increased production of lactic acid

   3. Systemic acidosis

Irreversible

Stage of shock

1. Fall in peripheral resistance

2. Multiple organ dysfunction

Hypotension, tachycardia, decreased urine output, hypothermia, can progress to DIC

Clinical signs of shock

Edema, petechial hemorrhages, microthrombi, pooling of blood

Gross changes seen in shock

Lungs, larynx

Shock organs (where blood is most likely to pool) in cats

Liver, GI tract

Shock organs (where blood is most likely to pool) in dogs

Lungs

Shock organs (where blood is most likely to pool) in pigs and ruminants

GI tract

Shock organ (where blood is most likely to pool) in horses