Hemodynamics Disorders, Guest Lecture 1

General Pathology

Proper functioning of blood vessels is critical for providing oxygen and nutrients to cell and tissues, and for the removal of waste, which is important for what kind of homeostasis?

Fluid homeostasis

What are some characteristics of ideal blood vessles?

1. Strong/durable

2. Keeps blood in and other things out

3. Adaptive tissue-specific distribution of blood

4. Efficient return of blood from organs

5. Ability to control blood flow when something goes wrong

6. Consistent flow without obstructions

Structural leakiness of a blood vessel can result in:

Hemorrhage

Non-structural leakiness of a blood vessel can result in:

Edema

Too much or too little blood flow results in:

Hyperemia/shock

Not enough clotting can cause:

impaired hemostasis

Too much clotting (blockage) can cause:

Thrombosis/embolism

Too little blood flow out of the tissue can cause:

Congestion

What are the two types of abnormal fluid homeostasis?

1. True dysfunction (not working from the start)

2. Result/failure of attempted adaptive compensatory/homeostatic mechanism address another tissue (body is trying to compenstate)

This is the increase of blood volume within tissues:

Hyperemia

How is hyperemia caused?

Arteriolar dilation (active, adaptive process)

What are 2 examples of hyperemia?

Sites of inflammation (conjunctivitis)

Exercising skeletal muscles

This is increased blood volume within tissue (but not good) and is a passive, generally is a pathologic process:

congestion

Congestion typically is caused by:

1. Impaired flow (extra blood collected in the organ)

What are some examples of congestion?

1. Cardiac failure, leading to hepatic or pulmonary congestion (NUTMEG LIVER)

2. Venous obstruction

This is the accumulation of interstitial fluid in tissues (typically subcutaneous)

Edema

This is severe, generalized edema

Anasarca

This is interstitial fluid within body cavities (pleural or pericardial effusion, ascites/peritoneal effusion)

Effusion

What is a normal body fluid balance?

60% body weight = water

2/3 intracellular

1/3 extracellular

(most are interstitial, some blood plasma)

Edema results when:

Increased hydrostatic pressure or decreased osmotic pressure leads to net accumulation of fluid in interstitium (lymphatic return)

What would cause an increase in hydrostatic pressure, which leads to edema?

1. Venous obstruction/impaired venous return (DVT, obstructed venous outflow, lower extremity inactivity, cirrhosis)

2. Generalized, congestive heart failure (increased hydrostatic pressure in alveolar capillaries due to left ventricular pulmonary edema and eventually peripheral edema)

3. Arteriolar dilation (heat/neurohumoral dysfunciton)

What could cause a decrease in plasma osmotic pressure, which leads to edema (net flow of fluid out of vessel and into tissue)?

A loss of albumin (critical for maintaining POP)

1. Loss of existing albumin (urinary, nephrotic syndrome)

2. Decreased albumin synthesis (in the liver)

3. Insufficient raw materials (protein malnutrition)

4. Insufficient machinery (cirrhosis)

How can lymphatic obstruction lead to edema?

The mechanism of normal flow of fluid out of interstitial tissue into the lymphatics is compromised, increasing interstitial fluid

What can cause a lymphatic obstruction (which leads to edema)?

1. Infections/inflammatory filariasis (parasite)

2. Neoplastic (bulky tumor blocks lymphatic return)

3. Post-surgical radiation (mastectomy with lymph node dissection or radiation leading to lymphedema)

How can sodium and water retention cause edema?

Mechanism is the increase in salt causes an increase intravascular volume, which increases hydrostatic pressure and a decrease in POP. this leads to a new flow of fluid out of the vessel and into the tissue

What can cause sodium and water retention, that leads to edema?

1. Acute kidney injury

What are common causes of hemorrhage?

Trauma

Weakening of wall (atherosclerosis, inflammation, aneurysm)

Erosion of wall (neoplastic erosion)

Chronic congestion (pulmonary and hepatic congestion)

Predisposition to hemorrhage with minimal trauma (clotting disorders)

this is defined as extravasation of blood vessels (can be internal or external)

Hemorrhage

Accumulation of hemorrhage within a space

Hematoma

What are a few examples of hematomas?

Hemopericardium

Hemothorax

Hemoperitoneum

Hemarthrosis (joints)

Subdural hematoma

Ecchymosis (bruise)

Small (1-2 cm) hemorrhages into skin, mucosa, or serosa

Petechiae

What are causes of petechiae?

Thrombocytopenia

Platelet dysfunction

Loss of vascular wall support

Vitamin C deficiency

Medium-sized (3-5 mm) hemorrhages into skin, or serosa

Purpura

What are some causes of purpura?

Same as petechiae

Trauma

Vasculitis

Vascular fragility

What are the 4 steps of hemostasis?

1. Arteriolar vasoconstriction

2. Primary hemostasis (platelet plug formation)

3. Secondary hemostasis (fibrin deposition, coagulation cascade)

4. Clot stabilization

What is the ultimate goal of hemostasis?

To form a blood clot at the site of injury to limit the extent of bleeding

Impaired hemostasis can be caused by defects in:

1. Vascular integrity

2. Platelet count or function

3. vWF deficiency or dysfunction

4. Clotting factor deficiencies/inhibition (hemophilia, liver disease, anticoagulants)

what can cause endothelial injury?

1. Trauma

2. Surgery

3. Burn

4. Ulcerated atherosclerotic plaques

5. vasculitis

6. smoking

7. Sepsis

What can cause abnormal blood flow?

1. Atherosclerosis

2. Prolonged bed rest

3. Atrial fibrillation

4. Myocardial infarct

5. Prosthetic heart valves

6. Aneurysms

this is a formation of a blood clot within intact vessels. It begins at the site of endothelial injury, turbulence of flow, or blood stasis (point attachment to wall)

Thrombosis

Laminations grossly or microscopically produced by alternating layers of platelets, fibrin, RBCs

Lines of Zahn

What are the causes of venous thrombosis?

1. immobilization (post-op, long car or plane ride, congestive heart failure)

2. Trauma, surgery, burns

3. Pregnancy

4. Malignancy (migratory thrombophlebitis, Trousseau)

Where does venous thrombosis typically occur?

Lower extremities

Thrombosis found in superficial veins (saphenous vein system) do what?

rarely embolize

This is a detached intravascular mass carried by blood to a distant site (infarction)

Embolism

What are some examples of thromboembolisms?

1. DVT to lungs, PULMONARY EMBOLISM

2. Right heart/valve to lungs, PULMONARY EMBOLISM

3. Left heart/valve to systemic arterial circulation, INFARCTION (brain, extremities, intestines, kidney, spleen)

4. Atherosclerotic plaque, aorta to legs/carotid artery to brain

5. Fat (fractures of long bones, soft tissue trauma)

6. Air obstetric procedures, chest injuries, divers (decompression sickness)

7. Amniotic fluid (during delivery)

8. Tumor

This is characterized by initial clotting (microangiopathy), resulting in organ ischemia, followed by bleeding tendencies

Disseminated intravascular coagulation (DIC)

This is widespread clotting leads to consumption of factors and platelets

Consumptive coagulopathy

Disseminated intravascular coagulation is associated with severe illnesses, such as:

1. Sepsis

2. Trauma

3. Obstetric complications

4. Fat embolus

5. Cancer (acute promyelocytic leukemia)

6. Burns

7. Ischemia

An infarction is an occlusion of arterial supply/venous drainage, which leads to:

Ischemic necrosis

An infarction is typically arterial and due to a:

thrombosis/emolism

A red infarct occurs in:

1. Loose tissues (allows blood to collect)

2. Dual circulation tissues (Lung: bronchial/pulmonary arteries)

3. When flow is re-established (reperfusion due to break up of embolus)

4. Venous occlusions

A white infarct occurs in (non-hemorrhagic):

Solid organs with end-arterial circulation (spleen/kidney)

This is necrosis caused by the dead tissues being preserved, leading to eventual scar formation:

Ischemic coagulative necrosis

this is necrosis caused by dead cells being digested and turning into a liquid mass, causing eventual cavity (in brain and septic infarcts)

Liquefactive necrosis

Cardiovascular collapse is:

Shock

What are the steps of shock?

1. Systemic hypoperfusion

2. Cellular hypoxia

3. Tissue injury

4. Death

What 3 major types of shock?

1. Cardiogenic

2. Hypovolemic

3. Septic

What mechanisms lead to cardiogenic shock?

1. Failure of myocardial pump secondary to:

Intrinsic myocardial damage

Extrinsic pressure

Obstruction to outflow

What are some clinical examples of cardiogenic shock?

1. Myocardial infarction

2. Ventricular rupture

3. Arrhythmia

4. Cardiac tamponade

5. Pulmonary embolism

What is the mechanism for hypovolemic shock?

Inadequate blood or plasma volume

What are 2 examples of hypovolemic shock?

1. Hemorrhage

2. Fluid loss (burns, vomiting, diarrhea)

What is the mechanism that causes septic shock?

1. Peripheral vasodilation and pooling of blood

2. Endothelial activation or injury

3. Leukocyte-induced damage

4. Cytokine activation and disseminated intravascular coagulation

What is a clinical example of something that could lead to septic shock?

Overwhelming microbial infection (bacterial or fungus)

This type of shock is an interruption of sympathetic vasomotor output with a spinal cord injury, which leads to arteriolar and venous dilation, and decreased cardiac output

Neurogenic shock

this type of shock is a IgE mediated hypersensitivity response, which causes systemic vasodilation and increased vascular permeability

Anaphylactic shock

These types of shock leads to hypotension, tachycardia, tachypnea and cool, clammy, cyanotic skin

Hypovolemic

Cardiogenic

this kind of shock leads to hypotension, tachycardia, tachypnea and peripheral vasodilation initially (skin is warm and flushed)

Septic

Shock leads to multi-organ failure, primarily due to hypoxia, what can be seen in the organs?

1. Brain: hypoxic/ischemic encephalopathy

2. Heart: Subendocardial infarcts

3. Kidneys: Acute tubular necrosis

4. GI tract: Mucosual hemorrhages and bowel infarction

5. Liver: central hemorrhagic necrosis

6. Lungs: diffuse alveolar damage

7. Adrenal glands: cortical lipid cell depletion