Pathophysiology: Hemodynamic Disorders Pt 2 (thromboembolic disease, other forms of arterial occlusion, ischemia and infarction, shock) (does not have all essays)

Clotting (hemostasis) general overview

vasoconstriction, primary hemostasis forms platelet plug, secondary hemostasis leads to propagation of coagulation cascade/deposition of fibrin, antithrombotic mechanisms, removal of a clot by fibrinolysis

Two main coagulation cascade pathways which converge on the common pathway

contact activation (intrinsic), tissue factor (extrinsic)

How do we measure the intrinsic pathway?

PTT

How do we measure the extrinsic pathway?

PT/INR

thrombus

stationary blood clot

embolus

blood clot that travels

thromboembolism

both stationary and traveling, i.e. stationary blood clot that breaks off and travels from one site to another

Deep vein thrombosis (DVT) has high risk of....

pulmonary embolism (PE)

Phlebitis

inflammation of a vein

Virchow's triad refers to...

classic causes/predispositions for thrombus formation (arterial and venous)

What does Virchow's triad include?

endothelial injury, altered blood flow due to stasis or turbulent flow, hypercoagulable state

Venous thrombi over start at the _______ and are usually an _______ thrombus

valves, occlusive

Thrombi can be classified by their _______

content

Red thrombi are due to _________

stasis

Red thrombi are more often _______

venous

Red thrombi have more _____ enmeshed in clot

RBCs

White thrombi are more often _______

arterial

White thrombi have more ________/_______ in the clot

platelets, fibrin

What are consequences of venous occlusion?

-symptoms of edema and pain

-tissue infarction by embolization to next capillary bed

-venous back pressure leading to reduced arterial perfusion

-leakage of fibrin that inhibits oxygen perfusion

What are consequences of arterial occlusion?

-infarction and/or dysfunction of the tissue perfused by that artery

-if infarction occurs the tissue will undergo necrosis, scarring, and atrophy

-can embolize distally to the next capillary bed (i.e. carotid bifurcation thrombus can go to brain and lead to ischemic stroke or TIA

What is the fate of thrombi (what could happen to it)?

-may resolve/dissolve

-completely occlude the lumen and infarct tissue supplied by vessel

-may break off and embolize to the next capillary bed

-organize/recanalize

-propagate and accumulate additional platelets/fibrins and extend

-become infected and lead to septic thrombus/embolus

Where do a large majority of venous emboli arise from?

deep lower extremity proximal veins

deep lower extremity proximal veins examples (3)

iliac, femoral, popliteal

Majority of venous emboli will then go where?

pulmonary arteries

Paradoxical embolus

embolus gets to systemic circulation through an abnormal communication between the venous and arterial system, often at the level of the heart

Where do arterial thrombi often arise in?

heart chambers, often left side of the heart, arteries

Risk factors for arterial thrombi

Atrial fibrillation, endocarditis, MI, valve abnormalities

When do arterial thrombi arise in arteries?

complicated atherosclerotic plaques, sites of aneurysm formation

What are the most common sites of embolization in arterial thrombi?

lower extremities and brain

What are the 5 special forms of emboli?

fat emboli, atheroemboli (cholesterol crystal emboli), air embolus, amniotic fluid embolism, foreign body embolism

fat emboli

fat globules enter vascular space and obstruct, fat comes from bone marrow released during fractures, especially femur or pelvic fractures

Damage from fat emboli occurs from...

mechanical obstruction, biochemical injury

What areas do fat emboli affect?

lungs (pulmonary) and brain (CNS)

Atheroemboli

come from disrupted atherosclerotic plaque

air embolus

air enters circulation and forms a frothy mass obstructing flow due to iatrogenic causes

air embolus can lead to ________ sickness

decompression

What happens in decompression sickness?

nitrogen gas is dissolved/pushed into blood tissues, dissolved nitrogen gas is released on ascension, creating bubbles if ascension occurs too rapidly

Amniotic fluid embolism

fetal cells and debris enter the maternal circulation via a tear in placental membranes or ruptured uterine veins, occurs at end of labor and is catastrophic

What can Amniotic fluid embolism lead to?

DIC

Amniotic fluid embolism is not from embolic obstruction, but from _______ ________

maternal reaction

What might you see with Amniotic fluid embolism?

maternal pulmonary compromise with cyanosis, shock, coma

Foreign body embolism

bone cement especially during vertebroplasty, Talc in IV drug users, cotton, tumor, bullet/shrapnel fragments

If arterial spasm is severe, can lead to _________ that can cause tissue ________ or death

vasoconstriction, ischemia

relaxation of arterial spasm is normally mediated by ________ cells

endothelial

What do endothelial cells produce that relaxes vascular SMC?

prostacyclin and nitric oxide (NO)

Examples of specific conditions with arterial vasospasm

coronary spasm (leads to prinzmetal angina)

cerebral arterial spasm

cocaine use

stress ulcers of stomach

raynaud's phenomenon

_______ syndrome occurs from perfusion pressure falling below tissue pressure in a closed anatomic site (venous congestion leads to decreased arterial perfusion)

compartment

Where does compartment syndrome occur at in the body typically?

enclosed compartments in the extremities; forearm and lower leg

Compartment syndrome is often due to what?

major trauma, exercise, casts, tight fitting garments, drug addicts, snake bites

Running can lead to a _________ exertional compartment syndrome

chronic

The 5 (or 6) P's of Compartment Syndrome

pain, paresthesias, pallor, paralysis, pulselessness, poikilothermia (cold skin)

What is a possible complication of compartment syndrome?

Volkmann's contracture

Volkmann's contracture

deformation of forearm with flexion at wrist, follows infarction of muscle with replacement by fibrous tissue

Most cases of compartment syndrome that are diagnosed and treated early have what outcome?

good functional and cosmetic results

Torsion occurs in organs that have blood supplied by a _______ ______

vascular pedicle

Torsion may cause ______

infarction

What happens in torsion?

twisting of the vascular pedicle causes venous obstruction first then further twisting causes arterial obstruction

What is a similar condition to torsion that can be seen with a hernia?

strangulation

Ischemia

decreased blood supply to an organ

clinical effects of arterial ischemia depends on formation or presence of a...

collateral blood supply

_________ arteries have limited ability to form collaterals

terminal

Where are terminal arteries seen?

kidney, heart, brain (distal to circle of willis), spleen, and retina

acute ischemia

limits the possibility of compensation/collateral formation

chronic ischemia

allows time for compensation/collateral vessel formation

global ischemia occurs with ______ ______ failure

heart pump

infarction

area of ischemic cell/tissue death leading to coagulative necrosis, most often developing in the area distal to the occlusion of an arterial supply

__________ necrosis happens if brain infarction

liquefactive

What is infarction usually due to?

acute arterial thrombotic and/or embolic event

Infarction can also occur with occlusion of venous outflow, but it is much less _______

common

Whether an infarct occurs or not, it depends on what things?

type of vascular supply (terminal artery or dual blood supply, congenital anatomic collaterals)

rate of development of occlusion

vulnerability of tissue to hypoxia

oxygen content of the blood

White (pale) infarcts are often seen where?

heart (if no reperfusion), kidneys, spleen

Red infarcts are often due to what?

damage to the endothelium and subsequent hemorrhage in the infarct, occlusion of arterial or venous circulation

Red infarcts are seen in organs with...

dual blood supply or abundant collateral circulation

Examples of organs with dual blood supply or abundant collateral circulation

lung and liver (dual blood)

brain and small intestine (collateral flow)

heart (following reperfusion)

What happens to infarcts?

tissue organ/dysfunction, scarring, cystic area formation, liquefactive necrosis in brain, septic infarct

Shock is ________ collapse

cardiovascular

Shock is the condition in which..

myocardial pump failure or reduced effective circulating volume diminishes cardiac output impairing tissue perfusion leading to cellular/tissue hypoxia

Tissue perfusion depends on systemic _________ ________ (tubes) and _________ ________

vascular resistance, cardiac output

Cardiac output = _______ x _______

heart rate (HR), stroke volume (SV)

Stroke volume depends on what two things?

preload (liquid)

ability of heart to contract (pump)

Early on in shock, we can see compensation with:

tachycardia, cold pale skin from peripheral vasoconstriction

Compensatory mechanisms can fail and cause:

impaired tissue perfusion and cellular hypoxia

Tissue hypoperfusion from shock can cause what series of events?

tissue hypoperfusion, cellular hypoxia and metabolic derangements, organ dysfunction, organ failure and death

Hypoxia causes endothelial cells to be injured and become more permeable with loss of _________ fluid

intravascular

What does a loss of intravascular fluid cause?

decreased blood volume and venous cardiac return leading to a decrease in cardiac output

If the kidneys are not perfused, patient can become ______

acidotic

What are some common types of shock?

cardiogenic, hypovolemic, shock associated with systemic inflammation, anaphylactic, neurogenic

cardiogenic shock is due to..

myocardial pump failure

hypovolemic shock is due to...

decreased blood volume

shock associated with systemic inflammation is triggered by what things?

microbial infections leading to septic shock, non-microbial causes such as burns, trauma, pancreatitis, CAR-T therapy (cytokine release syndrome, CRS)

Shock associated with inflammation are all associated with a massive outpouring of _______ ________ from immune cells

inflammatory mediators

What is anaphylactic shock due to?

type I IgE mediated hypersensitivity

What is neurogenic shock due to?

severe brain or spinal cord injury which impairs vasomotor control and cannot vasoconstrict

Systemic Inflammatory Response Syndrome (SIRS)

response to an infection but can be seen with multiple other non infectious conditions, less specific definition than sepsis

Systemic Inflammatory Response Syndrome (SIRS) is clinically defined by:

temperature greater than 38 C or less than 36 C

heart rate greater than 90 bpm

respiratory rate greater than 20 bpm

WBC greater than 12,000 cells/mm (left shift)

New belief that SIRS is a form of ________ _________

dysregulated inflammation

Sepsis

life threatening organ dysfunction caused by a dysregulated host response to infection

septic shock

subset of sepsis in which particularly circulatory, cellular, and metabolic abnormalities are associated with greater risk of mortality than sepsis alone

(T/F) You do not have to have bacteria in the blood to meet criteria for sepsis

True

Septic shock mortality rate

50%