Pathology of ARDS/Shock/DIC Flashcards
Acute lung injury can demonstrate itself as?
Acute lung injury (non-cardiogenic pulmonary edema) can demonstrate itself clinically as acute respiratory distress syndrome (ARDS).
ARDS shows biologic changes in the lung called diffuse alveolar damage (DAD). Any or all of the names can somewhat be used interchangeably and loosely, although DAD is used much more frequently used by pathologists because it describes the visual pathobiology.
Clinically ARDS patients have what? examples?
Clinically, patients with ARDS often have some other precipitating condition that predisposes to its development:
Infections – Shock, sepsis, aspiration, diffuse infectious pneumonia
Trauma or other physical, chemical, radiation injury
Drug reactions – ASA, barbiturates, paraquat
Hematologic disease – Disseminated intravascular coagulation (DIC), transfusionassociated lung injury (TRALI)
What happens clinically during ARDS?
During their complicated clinical courses, these patients may begin to experience the severe/acute onset of pulmonary disease indicative of ARDS:
Dyspnea
Tachypnea
Hypoxemia
Cyanosis
Use of accessory respiratory muscles
CXR: bilateral lung opacity (“white out”)
Explain the pathogenesis of ARDS?
The pathogenesis of ARDS is complex and not totally understood. It is a patterned lung reaction, it may or may not occur in a given scenario, and it’s difficult to predict in which patients it will evolve. The steps are likely as follows:
Endothelial cells and/or alveolar macrophages become injured and/or activated, and begin to release immune-promoting mediators, procoagulant proteins, cytokines of all types, etc.
Both a local (pulmonary) and systemic immune reaction begin to occur
Neutrophils begin to migrate into the pulmonary parenchyma from the capillaries in the alveolar septum walls (the location where diffusion of oxygen into RBC’s occurs), and they degranulate, amplifying the immune response
Other cells migrate to the area, vessels become leaky, and abundant fluid leaks from the capillaries into the alveolar spaces
All of these new cells, and the formation of hyaline membranes, completes the biologic picture of diffuse alveolar damage. DAD is a great example of a biologic truism: Sometimes the immune response is more detrimental than the initiating insult
Explain the images?
Right image: The lungs become filled with fluid and cells, leading to a pale, firm, and rubbery appearance.
Left image: Classic-appearing DAD, characterized by eosinophilic hyaline membranes (arrow) lining alveolar spaces, increased cellularity, and variable alveolar collapse or expansion. Hyaline membranes are made up of fibrin, lipids from dead and dying cells, edema fluid, and other plasma proteins. This image is from an early DAD (ie., it isn’t that severe), and as hyaline membranes become more numerous and thicker, they will cause an ever-increasing, lifethreatening barrier to adequate oxygen diffusion from the alveolar space into the septal capillaries.
What is shock? What are some types and their features?
Shock is a state of systemic hypoperfusion resulting from a reduction in either cardiac output or the effective circulating blood volume. It is a final common pathway for many lethal events, such as severe hemorrhage, extensive trauma, large myocardial infarction, massive pulmonary embolism, and septicemia. The end result is hypotension, followed by impaired tissue perfusion and cellular hypoxia. There are several categories of shock, and some are:
1) Cardiogenic shock shows low cardiac output due to outflow obstruction (PE) or myocardial pump failure (myocardial infarction, arrhythmia, or pericardial tamponade)
2) Hypovolemic shock shows low cardiac output due to extensive hemorrhage and/or fluid loss (burns, trauma, vomiting, diarrhea)
3) Septic shock shows low cardiac output due to vasodilation and peripheral blood pooling caused by overwhelming microbial infection and associated immune response
4) Neurogenic shock is a rarer cause with loss of vascular tone and peripheral pooling (anesthetic accident, spinal cord injury)
5) Anaphylactic shock is a rarer cause with systemic vasodilation and increased vascular permeability (IgE-mediated hypersensitivity)
Septic shock implications?
Of all the shock categories above, septic shock may be the most elusive, in terms of its evolution and management. With a mortality rate of 20% and over 200,000 deaths per year due to septic shock, it is the #1 cause of death in intensive care units. Its incidence is also increasing, due to better life-saving measures, increasing age of patients, and increasing numbers of immunocompromised patients.
Septic shock is usually caused by?
Diverse microorganisms can cause shock, although it is most common following infection with gram positive bacteria, gram-negative bacteria and fungi. These infections trigger complex host reactions involving neutrophils, macrophages, endothelium, plasma cells, complement, etc. By incompletely understood mechanisms, septic shock (as an undesired immune/inflammatory response) can also unfortunately develop.
Explain The factors that can lead to septic shock?
Inflammatory and counter-inflammatory responses are generated
Endothelial cell activation/injury leads to an adhesive, procoagulant endothelial cell phenotype with markedly increased thrombotic tendencies, vasodilation, vascular permeability, and edema: DIC results in up to 50% of patients
Metabolic abnormalities include inflammatory cytokines (TNF and IL-1), stressinduced hormones (glucagon, growth hormone, and glucocorticoids) and catecholamines that collectively act to induce insulin resistance, hyperglycemia, and (over time) adrenal insufficiency. Adrenal gland necrosis due to DIC is named Waterhouse-Friderichson syndrome
Organ dysfunction ensues when systemic hypotension, interstitial edema, and small vessel thrombosis all conspire to decrease oxygen delivery to tissues. o Diminished cardiac contractility (due to high levels of cytokines and secondary mediators) and cardiac output lead to cardiovascular collapse o Increased vascular permeability and endothelial injury lead to lung failure and acute respiratory distress syndrome o Anuria can develop due to acute tubular necrosis and renal failure o Multiorgan failure involving liver, adrenals, etc. can result
The outcome of septic shock? what factors influence this?
The outcome of septic shock is variable (like its generation) and it’s a tough clinical challenge. Ultimately, an unknown combination of the 1) extent and virulence of the infection; 2) the host’s immune status; 3) the presence of other co-morbid conditions; and 4) the intricacies of tissue mediator production will unfold in a manner that may be very difficult to influence.
Phases of shock (any shock)?
For shock in which the mechanism is relatively clear, its evolution can be dividing into three (arbitrary) phases:
A non-progressive stage occurs in which reflex neurohumoral compensatory mechanisms are activated (catecholamines, ADH, renin-angiotensin axis, etc.) producing tachycardia, peripheral vasoconstriction, and renal conservation of fluid. Perfusion of vital organs can therefore be maintained.
A progressive stage occurs when persistent hypoxemia leads to anaerobic glycolysis, lactic acid generation, and decreased tissue pH, all which blunt the vasomotor response. This ultimately leads to vasodilation, peripheral pooling, worsening cardiac output, and increasing tissue hypoxia.
An irreversible stage has begun when re-perfusion will not correct the death spiral. Ischemic bowel may lead to superimposed bacteremia/septic shock; renal failure and acute tubular necrosis can lead to anuria.
Explain the morphology of shock?
Changes in many organs/cells are similar, but not identical, to those of ischemia. Certain tissues are just more vulnerable than others to shock-induced changes, and show the following:
Lungs – diffuse alveolar damage (“shock lung”) can be seen with sepsis or trauma; usually NOT seen in pure hypovolemic shock; histopathology includes hyaline membranes that line alveolar spaces with associated interstitial inflammation and pneumocyte proliferation. Said again, DAD is a patterned reaction, and this is why is can be seen in other clinical scenarios (ARDS).
Kidneys – extensive tubular ischemic injury (acute tubular necrosis) causes oliguria, anuria, and electrolyte disturbances; histopathology shows swollen, vacuolated tubular cells in association with tubular cell necrosis and tubular casts (early cast at arrow).
Explain the morphology of shock in the adrenals, GI tract, Brain, Skin/serosa?
Adrenals – cortical cell lipid depletion as stored lipids are used for the synthesis of steroids.
Gastrointestinal tract – ischemia with mucosal necrosis/breakdown
Brain – neuronal ischemic changes (red neurons) and neuronal loss
Skin/serosa – petechial hemorrhage as platelets and coagulation factors are consumed
Microthrombi seen anywhere in circulation if DIC is superimposed
DIC is what?
DIC is an acute, subacute, or chronic thrombohemorrhagic disorder characterized by the excessive activation of coagulation and the formation of thrombi in the microvasculature of the body. Like ARDS and sepsis, DIC is not a primary disease but a secondary response to disease or a secondary disease event.
Triggers for DIC?
In bacterial infections, endotoxins can inhibit the endothelial expression of thrombomodulin directly or indirectly by stimulating immune cells to make TNF o Endotoxins can activate factor XII
Antigen-antibody complexes formed in response (to an infection) can activate the classical complement pathway, giving rise to complement fragments that secondarily activate both platelets and granulocytes
In massive trauma, extensive surgery, and severe burns, tissue factor is released in abundance
In obstetric conditions, procoagulants derived from the placenta, dead/retained fetus, or amniotic fluid may enter the circulation
Hypoxia, acidosis, and shock often coexist in ill patients and can cause/exacerbate widespread endothelial injury/activation
Acute promyelocytic leukemia and adenocarcinomas (of lung, pancreas, colon, and stomach) are most likely to have tumor-related DIC, due to circulating tumor proteins
