16: Critical Care Flashcards
Where is the ventilation/perfusion ratio the highest and lowest in the lung?
Highest in the upper lobes and lowest in the lower lobes
What is the most potent stimulus for systemic inflammatory response syndrome (SIRS)?
Endotoxin (lipopolysaccharide lipid A)
[Lipid A is a very potent stimulatory of TNF release. Inflammatory response is activated systemically (TNF-alpha and IL-1 are major components) and results in capillary leakage, microvascular thrombi, hypotension, and eventually end-organ dysfunction.]
What are the 2 primary determinants of myocardial oxygen consumption?
- Increased ventricular wall tension (#1 determinant)
- Heart rate
[Can lead to myocardial ischemia.]
What results from stimulation of Beta 1 and 2 receptors?
- Beta 1: Increased myocardial contraction and rate
- Beta 2: Vascular smooth muscle and bronchial smooth muscle relaxation
[Beta 2 receptor stimulation also increases insulin, glucagon, and renin.]
What are the 4 Berlin criteria for acute respiratory distress syndrome (ARDS)?
- Acute onset (within 1 week of known clinical insult or 1 week of worsening symptoms)
- Bilateral pulmonary infiltrates (consistent with pulmonary edema)
- Carrico index (PaO2/FiO2) < 300 (mild 200-300, moderate 100-200, severe < 100)
- Absence of heart failure (wedge pressure < 18 mmHg)
Which hormones are the rapid and sustained neurohormonal responses to hypovolemia mediated by?
Rapid: Epinephrine and norepinephrine (Vasoconstriction and increased cardiac activity)
Sustained: Renin (vasoconstriction and water resorption), ADH (water resorption), and ACTH (cortisol release)
What are the effects of Dopamine infusion at the below doses?
- Low dose (2-5 ug/kg/min):
- Medium dose (6-10 ug/kg/min):
- High dose (>10 ug/kg/min):
- Low dose (2-5 ug/kg/min): Dopaminergic - Increase in renal blood flow
- Medium dose (6-10 ug/kg/min): Beta-adrenergic - Increased heart contractility
- High dose (>10 ug/kg/min): Alpha-adrenergic - Vasoconstriction and increased BP
[UpToDate: dopamine dilates the interlobular arteries and both the afferent (preglomerular) and efferent (postglomerular) arterioles. The net effect is a relatively large increase in renal blood flow with a lesser or no elevation in glomerular filtration rate. At higher concentrations (above 5 mcg/kg per minute), dopamine induces renal vasoconstriction.]
What is the effect of hydralazine infusion?
Alpha-blocker; Lowers blood pressure
[UpToDate: Direct vasodilation of arterioles (with little effect on veins) with decreased systemic resistance.]
What do the following equations equal:
- Cardiac output (CO) x Systemic vascular resistance (SVR)
- Cardiac output (CO) x Body surface area (BSA)
- Cardiac output (CO) x Systemic vascular resistance (SVR) = Mean arterial pressure (MAP)
- Cardiac output (CO) x Body surface area (BSA) = Cardiac index (CI)
What is the effect of Vasopressin mediated by the below receptors?
- V-1:
- Intrarenal V-2:
- Extrarenal V-2:
- V-1: Vasoconstriction of vascular smooth muscle
- Intrarenal V-2: Water reabsorption at collecting ducts
- Extrarenal V-2: Mediation of release of factor VIII and von Wilebrand factor
[UpToDate: Vasopressin stimulates a family of arginine vasopressin (AVP) receptors, oxytocin receptors, and purinergic receptors (Russell 2011). Vasopressin, at therapeutic doses used for vasodilatory shock, stimulates the AVPR1a (or V1) receptor and increases systemic vascular resistance and mean arterial blood pressure; in response to these effects, a decrease in heart rate and cardiac output may be seen. When the AVPR2 (or V2) receptor is stimulated, cyclic adenosine monophosphate (cAMP) increases which in turn increases water permeability at the renal tubule resulting in decreased urine volume and increased osmolality. Vasopressin, at pressor doses, also causes smooth muscle contraction in the GI tract by stimulating muscular V1 receptors and release of prolactin and ACTH via AVPR1b (or V3) receptors.]
Which condition do the following signs/symptoms characterize?
- Nausea and vomiting
- Thirst
- Polyuria
- Increased ketones
- Decreased sodium
- Increased potassium
- Increased glucose
Diabetic ketoacidosis
[Initial treatment is normal saline and insulin.]
Why is blood in the left ventricle oxygen content 5 mmHg lower than blood in the pulmonary capillaries?
Unsaturated bronchial blood empties into the pulmonary veins
What is the effect of isoproterenol infusion?
Beta 1&2-adrenergic (increased heart rate and contractility, vasodilation)
[Side effects: extremely arrhythmogenic; Increased heart metabolic demand (rarely used); may actually decrease blood pressure.]
[UpToDate: Stimulates beta1- and beta2-receptors resulting in relaxation of bronchial, GI, and uterine smooth muscle, increased heart rate and contractility, vasodilation of peripheral vasculature.]
What is the advantage of using continuous venovenous hemofiltration (CVVH) over hemodialysis?
CVVH is slower and better for ill patients who cannot tolerate the volume shifts (septic shock patients, etc.)
[Hematocrit increases by 5-8 for each liter taken off with dialysis.]
[UpToDate: Continuous renal replacement therapies (CRRTs) involve either dialysis (diffusion-based solute removal) or filtration (convection-based solute and water removal) treatments that operate in a continuous mode. The major advantage of continuous therapy is the slower rate of solute or fluid removal per unit of time. Thus, CRRT is generally better tolerated than conventional therapy since many of the complications of intermittent hemodialysis are related to the rapid rate of solute and fluid loss.
There are many variations of CRRT. The different modalities are categorized according to the access characteristics: blood or peritoneal, venovenous (VV) or arteriovenous (AV). A large number of acronyms have been derived that describe the different continuous therapies.
The choice of modality is dependent upon several factors including availability, the expertise of the clinician, hemodynamic stability, vascular access, and whether the primary need is for fluid and/or solute removal.]
What will be seen on electroencephalogram (EEG) and magnetic resonance angiography (MRA) in a patient with brain death?
- EEG: Electrical silence
- MRA: No blood flow to brain
Which disease states decrease pulmonary compliance?
- ARDS
- Fibrotic lung disease
- Reperfusion injury
- Pulmonary injury
- Atelectasis
[Compliance = (change in volume) / (change in pressure). High compliance means lungs are easy to ventilate.]
Do the below factors cause pulmonary vasoconstriction or vasodilation?
- PGE1:
- Prostacyclin (PGI2):
- Hypoxia:
- Histamine:
- Nitric oxide:
- Bradykinin:
- Serotonin:
- TXA2:
- Alkalosis:
- Acidosis:
- PGE1: Vasodilation
- Prostacyclin (PGI2): Vasodilation
- Hypoxia: Vasoconstriction
- Histamine: Vasoconstriction
- Nitric oxide: Vasodilation
- Bradykinin: Vasodilation
- Serotonin: Vasoconstriction
- TXA2: Vasoconstriction
- Alkalosis: Vasodilation
- Acidosis: Vasoconstriction
What is the treatment for neurogenic shock?
- Give volume 1st
- Give Phenylephrine after volume resuscitation
What are the below characteristics of antidiuretic hormone released?
- Where is it released:
- What triggers its release:
- What is its mechanism of action:
- Where is it released: Posterior pituitary gland
- What triggers its release: Released in response to high osmolality
- What is its mechanism of action: Acts on collecting ducts for water resorption. Also a vasoconstrictor
[UpToDate: In normal subjects, the urine output is primarily determined by water intake. Changes in water intake lead to alterations in the plasma osmolality that are sensed by the osmoreceptors in the hypothalamus that regulate both ADH release and thirst. As an example, an increase in water intake sequentially lowers the plasma osmolality, decreases ADH secretion, and reduces collecting tubule permeability to water; the net effect is the rapid excretion of the excess water in a dilute urine.
What is the normal p50 (O2 level at which 50% of O2 receptors are saturated)?
27 mmHg
What are the below characteristics of atrial natriuretic peptide released?
- Where is it released:
- What triggers its release:
- What is its mechanism of action:
- Where is it released: From wall of atrium
- What triggers its release: Released in response to atrial distension
- What is its mechanism of action: Inhibits Na and water resorption in the collecting ducts. Also a vasodilator
[UpToDate: Atrial natriuretic peptide (ANP) is primarily released from the atria in response to volume expansion, which is sensed as an increase in atrial stretch. ANP release is increased in heart failure. Plasma ANP levels rise early in the course of the disease and have been used as a marker for the diagnosis of asymptomatic left ventricular dysfunction. With chronic and more advanced heart failure, ventricular cells can also be recruited to secrete both ANP and brain natriuretic peptide (BNP), an analogous peptide, in response to the high ventricular filling pressures. These relationships have allowed the plasma concentration of these peptides, particularly BNP, to be used to detect heart failure and to predict the outcome and perhaps guide therapy in patients with established disease.
Both ANP and BNP have diuretic, natriuretic, and hypotensive effects. They also inhibit the renin-angiotensin system, endothelin secretion, and systemic and renal sympathetic activity. Among patients with HF, increased secretion of ANP and BNP may partially counteract the effects of norepinephrine, endothelin, and angiotensin II, limiting the degree of vasoconstriction and sodium retention. In one study of patients with moderately severe HF, for example, administration of an orally active inhibitor of the endopeptidase that degrades ANP led to reductions in plasma aldosterone concentrations and right ventricular (RV) and left ventricular (LV) filling pressures, as well as a decrease in body weight presumed to be due to diuresis, natriuresis, or both. These effects were presumably mediated by enhanced natriuretic peptide activity.
An unexpected finding is that BNP may protect against collagen accumulation and the pathologic remodeling that contributes to progressive HF. Studies in BNP knockout mice reveal increased cardiac fibrosis in response to ventricular pressure overload.]
What is the formula for calculating arterial O2 (CaO2) content?
CaO2 = Hgb x 1.34 x O2 saturation + (Po2 X 0.003)
[UpToDate: The arterial oxygen content (CaO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in arterial blood:
CaO2 (mL O2/dL) = (1.34 x hemoglobin concentration x SaO2) + (0.0031 x PaO2)
where SaO2 is the arterial oxyhemoglobin saturation and PaO2 is the arterial oxygen tension. In dyshemoglobinemias, the oxygen content is calculated with the same equation, although the saturations (and therefore the oxygen content) will be different for a specific PaO2. Normal CaO2 is approximately 20 mL O2/dL.
Similarly, the mixed venous blood oxygen content (CvO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in mixed venous blood:
CvO2 (mL O2/dL) = (1.34 x hemoglobin concentration x SvO2) + (0.0031 x PvO2)
where SvO2 is the mixed venous oxyhemoglobin saturation and PvO2 is the mixed venous oxygen tension. Normal CvO2 is approximately 15 mL O2/dL. Mixed venous blood is drawn from the right atrium. Peripheral venous blood should not be substituted because it tends to overestimate venous oxygen content.]
What is the effect of an intraaortic balloon pump (IABP) on the the below measures?
- Diastolic blood pressure
- Systolic blood pressure
- Coronary blood flow
- Afterload
- Diastolic blood pressure: +
- Systolic blood pressure: -
- Coronary blood flow: +
- Afterload: -
[Improved diastolic blood pressure improves coronary perfusion.]
[The hemodynamic effects of an intraaortic balloon pump depend upon the volume of the balloon, its position in the aorta, heart rate, rhythm, the compliance of the aorta, and systemic resistance. The higher the arterial elastance, which is determined in part by compliance, the greater the hemodynamic improvement from intraaortic balloon pump counterpulsation (IABP). Despite this variability, expected changes in the hemodynamic profile in the majority of patients with cardiogenic shock include:
- A decrease in systolic pressure by 20%
- An increase in aortic diastolic pressure by 30%, which may raise coronary blood flow to territory perfused by a vessel with a critical stenosis.
- An increase in mean arterial pressure especially in patients with shock due to an acute mechanical abnormality such as mitral regurgitation (MR) or ventricular septal defect (VSD) or to improvement in perfusion of a territory resulting in overall improved ventricular function.
- A reduction of the heart rate by less than 20%
- A decrease in the mean pulmonary capillary wedge pressure by 20%
- An elevation in the cardiac output by 20%, especially in patients with MR, VSD, or a large territory of medically refractory ischemia that is improved by the addition of counterpulsation
In addition, intraaortic balloon pumping reduces mean systemic impedance and developed systolic pressure, and causes a 14% decline in calculated peak left ventricular wall stress. The reductions in afterload and wall stress lead to a fall in myocardial oxygen consumption, which is one of the goals of treatment of patients with myocardial ischemia.]
What is the best test for azotemia (elevated nitrogen-containing compounds in the blood)?
Fractional excretion of sodium (FeNa)
[FeNa = (Urine sodium x Serum creatinine) / (Serum sodium x Urine creatinine) x 100]
[UpToDate: The fractional excretion of sodium (FENa) measures the percent of filtered sodium that is excreted in the urine. The FENa is commonly used to assist in differentiating prerenal disease (a reduction in glomerular filtration rate [GFR] due solely to decreased renal perfusion) from acute tubular necrosis (ATN), the two most common causes of acute kidney injury (AKI).
Among patients with suspected prerenal disease or ATN, we recommend measuring the FENa. A value of the FENa below 1% commonly indicates prerenal disease; in comparison, a value between 1 and 2 percent may be seen with either disorder, while a value above 2% usually indicates ATN.]
Where in the body does blood have the lowest venous oxygen saturation?
Coronary sinus
[30% oxygen saturation in the coronary sinus.]
What is the effect of phenylephrine infusion?
Alpha 1-adrenegic: Vasoconstriction
[UpToDate: Potent, direct-acting alpha-adrenergic agonist with virtually no beta-adrenergic activity; produces systemic arterial vasoconstriction. Such increases in systemic vascular resistance result in dose dependent increases in systolic and diastolic blood pressure and reductions in heart rate and cardiac output especially in patients with heart failure.]
What are the indications for an intraaortic balloon pump?
- Cardiogenic shock (after CABG or MI)
- In patients with refractory angina awaiting revascularization
[UpToDate: Consequent to the improvement in hemodynamic parameters described above, the intraaortic balloon pump counterpulsation (IABP) may be an effective temporary therapeutic option in patients with significant hemodynamic compromise resulting from myocardial ischemia.
However, some patients with hemodynamic instability may require other percutaneous support due to IABP failure or as initial therapy. For example, an axial flow pump or a percutaneous left atrial-to-femoral arterial ventricular assist device may be appropriate for patients with low output states or shock when an IABP is deemed unlikely to provide adequate support. IABP is used in a variety of clinical conditions:
- Cardiogenic shock (left ventricular failure or mechanical complications of an acute myocardial infarction)
- Intractable angina
- Low cardiac output after cardiopulmonary bypass
- Adjunctive therapy in high risk or complicated angioplasty
- Prophylaxis in patients with severe left main coronary arterial stenosis in whom surgery is pending
- Intractable myocardial ischemia awaiting further therapy
- Refractory heart failure as a bridge to further therapy
- Intractable ventricular arrhythmias as a bridge to further therapy
Intraaortic balloon pumping reduces electrocardiographic ST-segment abnormalities in patients with acute coronary syndromes, and is effective in the treatment of angina unresponsive to medical therapy that cannot be treated promptly with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). However, the availability of effective medical therapy and prompt revascularization has all but eliminated this indication. Rarely, patients with surgical disease and persistent ischemia do require IABP support pending surgery.]
Is acute adrenal insufficiency characteristically responsive or unresponsive to fluids and pressors?
Unresponsive
[Causes cardiovascular collapse.]
What is the normal value for the following:
- Pulmonary Artery Pressure (PAP)
- Pulmonary Capillary Wedge Pressure (PCWP)
- Pulmonary Artery Pressure (PAP) = 25/10 (+/-5)
- Pulmonary Capillary Wedge Pressure (PCWP) = 11 (+/-4)
[UpToDate: Normal pulmonary artery (PA) systolic pressures range from 15 to 25 mmHg, while PA diastolic pressures range from 8 to 15 mmHg. The mean PA pressure (mPAp) is typically 16 mmHg (10 to 22 mmHg). The mean PA pressure can be elevated (eg, mPAp, >22 mmHg) by acute conditions (eg, venous thromboembolism or hypoxemic-induced pulmonary vasoconstriction), by acute-on-chronic conditions (eg, hypoxemic-induced vasoconstriction in a patient with underlying chronic cardiopulmonary disease), or by chronic conditions (eg, pulmonary hypertension [PH]). Although PH is defined as a mPAp ≥25 mmHg, many of the etiologies associated with PH will also result in mild elevations of the PA pressure.
The pulmonary artery occlusion pressure (PAOP; pulmonary capillary wedge pressure [PCWP] or pulmonary artery wedge pressure [PAWP]) estimates the left atrial pressure. It is best measured with the patient in the supine position, at the end of expiration with the tip of the catheter in zone 3 of the lung. Ideally, the value is measured at least three times and the mean is calculated.
The PAOP tracing is obtained by inflating the balloon at the distal tip of the catheter. The balloon obstructs blood flow through a branch of the pulmonary artery. This creates a static column of blood between the catheter tip and the left atrium. Pressure at both ends of the column equilibrates, after which the pressure at the distal end of the catheter is equal to the pressure of the left atrium. Thus, PAOP is a reflection of left atrial pressure. Normal wedge pressures vary from 6 to 15 mmHg, with a mean of 9 mmHg.
Importantly, the PAOP usually estimates the left ventricular end-diastolic pressure (ie, left ventricular preload) if there is no obstruction to flow between the left atrium and left ventricle and the compliance of the left ventricle is normal. Importantly, it does not directly measure the left ventricular end-diastolic volume, capillary hydrostatic pressure, or transmural pressures. Thus, the PAOP may not reliably indicate left ventricular preload when compliance of the left ventricle is abnormal (eg, large myocardial infarction or in cardiac tamponade).]
How do the following characteristics change as one ages?
- FEV1:
- Vital capacity:
- Functional residual capacity:
- FEV1: Decreases
- Vital capacity: Decreases
- Functional residual capacity: Increases
What is the normal value for the following:
- Cardiac output (L/min)
- Cardiac Index (L/min)
- Cardiac output (L/min) = 4-8 L/min
- Cardiac Index (L/min) = 2.5-4 L/min
[UpToDate: The pulmonary artery catheter (PAC) measures the cardiac output (CO) via either the indicator thermodilution method or the Fick method. The preferred expression of CO is the cardiac index [CI], which is calculated by dividing the CO by the body surface area. Normal hemodynamic measures for CI are 2.8 to 4.2 L/min/m2. The causes of a low cardiac output include systolic and diastolic heart failure, but also include severe forms of mitral valve regurgitation, hypovolemia, pulmonary hypertension, and right ventricular failure. Distinguishing these pathologies from one another depends upon presenting clinical and echocardiographic features and well as specific patterns of physiologic variables seen on the PAC.]
What is the formula for calculating O2 consumption (VO2)?
VO2 = CO x (CaO2 - CvO2)
[CaO2 is arterial O2 content. CvO2 is venous O2 content.]
What can throw off the pulmonary capillary wedge pressure?
- Pulmonary hypertension
- Aortic regurgitation
- Mitral stenosis
- Mitral regurgitation
- High PEEP
- Poor LV compliance
[Wedge pressure measurements should be taken at end-expiration (for both ventilated and nonventilated patients.]
What percent of the left ventricular end-diastolic volume is accounted for by the atrial kick?
20%
Where do most pulmonary embolisms arise from?
The iliofemoral region
What is the treatment for an unstable patient with a pulmonary embolus?
Consider open or percutaneous suction catheter embolectomy if patient is in shock despite massive pressors and inotropes
[UpToDate: In patients with a high clinical suspicion for PE who are hemodynamically unstable and who have a definitive diagnosis by portable perfusion scanning or a presumptive diagnosis of PE by bedside echocardiography (because definitive diagnostic testing is unsafe or not feasible), we suggest systemic thrombolytic therapy rather than empiric anticoagulation or no therapy (Grade 2C). If bedside testing is delayed or unavailable, the use of thrombolytic therapy as a life-saving measure should be individualized; if not used, the patient should receive empiric anticoagulation. For patients who are hemodynamically unstable and the clinical suspicion is low or moderate, we suggest empiric anticoagulation similar to that suggested for patients who are hemodynamically stable; empiric thrombolysis is not justified in this population.]
Which enzyme in endothelial cells forms toxic oxygen radicals involved in reperfusion injury and which cell type is the most important mediator of reperfusion injury?
- Enzyme: Xanthine oxidase
- Most important mediator: Polymorphonucleocytes
[Xanthine oxidase is also involved in the metabolism of purines and breakdown to uric acid.]
What is the treatment for shock secondary to acute adrenal insufficiency?
Dexamethasone
What percent of cardiac output do the following organs receive:
- Kidneys
- Brain
- Heart
- Kidneys = 25%
- Brain = 15%
- Heart = 5%
What is the effect of milrinone infusion?
Increased myocardial contractility and pulmonary vasodilation
[Milrinone is a phosphodiesterase inhibitor which increases cAMP, resulting in increased calcium flux and increased myocardial contractility. It also causes vascular smooth muscle relaxation and pulmonary vasodilation.]
[UpToDate: A selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.]
What is the Bowditch effect?
Automatic increase in contractility secondary to increased heart rate
Which zone of the lung should a Swan-Ganz catheter be placed into?
Zone 3 (lower lung)
[UpToDate: The tip of the catheter should ideally be positioned in zone 3 (ie, below the level of the left atrium), such that PAOP will be overestimated if placed in zone 1 or 2.
The lungs can be divided into three physiologic zones of blood flow. These zones are based upon the alveolar pressure, mean pulmonary artery pressure, and pulmonary capillary pressure:
- Zone 1 is the least dependent zone. In this zone, the mean alveolar pressure exceeds the mean arterial pressure, which exceeds the mean pulmonary capillary pressure (PA>Pa>Pc).
- Zone 2 is the middle zone. In this zone, the mean arterial pressure exceeds the mean alveolar pressure, which exceeds the mean pulmonary capillary pressure (Pa>PA>Pc).
- Zone 3 is the most dependent zone. In this zone, the mean arterial pressure exceeds the mean pulmonary capillary pressure, which exceeds the alveolar pressure (Pa>Pc>PA).
Correct placement only occurs in approximately 30% of catheter insertions. Indicators that the catheter has been placed into a zone other than zone 3 include an abnormal position on the lateral chest radiograph (rarely performed in the intensive care unit), marked respiratory variation in the PAOP tracing, and an increase in the PAOP due to positive end-expiratory pressure that exceeds 50% of the amount of applied positive end-expiratory pressure.]
Which is more affect in critical illness neuropathy: motor or sensory neurons?
Motor neurons
[Can lead to failure to wean from ventilation.]
[UpToDate: The second neuromuscular condition that is commonly acquired in the intensive care unit (ICU) is critical illness polyneuropathy (CIP). This disorder was first recognized clinically in the late 1970s and 1980s.
Association with sepsis — Critical illness polyneuropathy appears to be a common complication of severe sepsis and is thought to represent a neurologic manifestation of the systemic inflammatory response syndrome (SIRS). There is some correlation with elevations in blood glucose and reductions in serum albumin.
The mechanism of axonal injury in CIP is unknown. However, speculation focuses on injury to the microcirculation of distal nerves, causing ischemia and axonal degeneration. During the early stages of sepsis, electrical inexcitability due to sodium channel inactivation may be present in otherwise intact nerves.
The association of sepsis with CIP is illustrated by a prospective report that assessed electrophysiologic and clinical data from 43 patients an average of 28 days after the onset of sepsis and multiorgan failure. An axonal polyneuropathy was present in 30 patients (70%), 15 of whom also had clinical evidence of generalized muscle dysfunction, characterized by limb muscle weakness, reduced or absent deep tendon reflexes, and/or delayed weaning from mechanical ventilation. Three severely affected patients were unable to move any of their extremities, failed to improve, and ultimately died.
Many patients with severe sepsis who develop neuromuscular weakness in the ICU have a combination of CIM and CIP.
In survivors of CIP with mild or moderate nerve injury, recovery of muscle strength generally occurs over weeks to months. However, electrodiagnostic testing may demonstrate residual nerve dysfunction several years after initial presentation. Patients with severe CIP may remain quadriplegic.]
What is the treatment for a stable patient with a pulmonary embolus?
Heparin, Coumadin
[UpToDate: For patients with suspected PE who are hemodynamically stable or hemodynamically unstable and successfully resuscitated, the administration of empiric anticoagulation depends upon the risk of bleeding, the clinical suspicion for PE, and the expected timing of diagnostic tests:
- For patients with a low risk of bleeding and a high clinical suspicion for PE, we suggest empiric anticoagulation rather than waiting until definitive diagnostic tests are completed (Grade 2C). We use a similar approach in those with a moderate or low clinical suspicion for PE in whom the diagnostic evaluation is expected to take longer than four hours and 24 hours, respectively.
- We do not anticoagulate patients with absolute contraindications to anticoagulant therapy or those with an unacceptably high risk of bleeding (Grade 1C).
- For patients with a moderate risk of bleeding, empiric anticoagulant therapy may be administered on a case-by-case basis according to the assessed risk-benefit ratio.]
What are the most common causes of ARDS?
- Pneumonia is most common
- Sepsis
- Multi-trauma
- Severe burns
- Pancreatitis
- Aspiration
- DIC
Renin is released in response to which two physiologic states and what mediates renin release in each?
- Decreased pressure sensed by the juxtoglomerular apparatus in the kidney
- Increased sodium concentration sensed by the macula densa in early distal tubule
[Beta-adrenergic stimulation and hyperkalemia also cause release.]
[UpToDate: Factors that regulate renin secretion are related to the classical actions of angiotensin II: increased sodium and water reabsorption; and systemic vasoconstriction. Short-term feedback of renin secretion is mediated via angiotensin II; angiotensin II binds to its receptor to inhibit renin gene expression. Long-term feedback of renin secretion is mediated by the physiologic cycle of angiotensin II; angiotensin II increases blood pressure and sodium retention, which then inhibits renin release.
The changes in extracellular fluid volume that govern renin release are primarily sensed at three sites:
- Baroreceptors (or stretch receptors) in the wall of the afferent arteriole
- Cardiac and arterial baroreceptors, which regulate sympathetic neural activity and the level of circulating catecholamines, both of which enhance renin secretion via the beta-1-adrenergic receptors
- The cells of the macula densa in the early distal tubule, which appear to be stimulated by a reduction in chloride delivery, particularly in the chloride concentration in the fluid delivered to this site
In normal subjects, the major determinant of renin secretion is sodium intake: a high intake expands the extracellular fluid volume and decreases renin release, whereas a low sodium intake (or sodium and water losses from any site) leads to a reduction in extracellular fluid volume and stimulation of renin secretion. Acute increases in renin secretion, such as those occurring with hypovolemia, primarily reflect the release of preformed renin from intracellular secretory granules. Chronic, persistent stimuli to renin release lead to increased synthesis of new prorenin and renin.
Increases in renin secretion produce increases in angiotensin II and aldosterone production, sodium reabsorption, and expansion of the extracellular fluid volume. By contrast, decreases in renin secretion produce decreases in angiotensin II and aldosterone production, sodium reabsorption, and reduction of the extracellular fluid volume. Intrarenal formation of angiotensin II probably plays at least a contributory role in the sodium retention induced by renin, as illustrated by the rise in messenger RNA for both renin and angiotensin substrate in the renal cortex following a low-sodium diet.]
Define the following terms:
- Total lung capacity (TLC):
- Forced vital capacity (FVC):
- Residual volume (RV):
- Tidal volume (TV):
- Functional residual capacity (FRC):
- Expiratory reserve volume (ERV):
- Inspiratory capacity:
- FEV1:
- Minute ventilation:
- Total lung capacity (TLC): Lung volume after maximal inspiration (TLC=FVC+RV)
- Forced vital capacity (FVC): Maximal exhalation after maximal inhalation
- Residual volume (RV): Lung volume after maximal expiration (20% of TLC)
- Tidal volume (TV): Volume of air with normal inspiration and expiration
- Functional residual capacity (FRC): Lung volume after normal exhalation (FRC=ERV+RV)
- Expiratory reserve volume (ERV): Volume of air that can be forcefully expired after normal expiration
- Inspiratory capacity: Maximum air breathed in from functional residual capacity
- FEV1: Forced expiratory volume in 1 second (after maximal inhalation)
- Minute ventilation: MV = TV x RR
How do the below pulmonary characteristics change in obstructive lung disease?
- Total lung capacity (TLC):
- Residual volume (RV):
- Forced vital capacity (FVC):
- Forced expiratory volume (FEV1):
- Total lung capacity (TLC): Increased
- Residual volume (RV): Increased
- Forced vital capacity (FVC): Normal or decreased
- Forced expiratory volume (FEV1): Decreased
What are the common causes of inaccurate pulse oximetry readings?
- Nail polish
- Dark skin
- Low-flow states
- Ambient light
- Anemia
- Vital dyes
Where are the below components of the Renin-angiotensin system made?
- Prorenin/Renin:
- Angiotensinogen:
- Angiotensinogen conversion to Angiotensin I:
- Angiotensin I conversion to Angiotensin II:
- Release of Aldosterone in response to Angiotensin II:
- Prorenin/Renin: Juxtoglomerular cells of kidney
- Angiotensinogen: Mainly synthesized by the liver
- Angiotensinogen conversion to Angiotensin I: Rate limiting step catalyzed by circulating renin
- Angiotensin I conversion to Angiotensin II: Angiotensin converting enzyme (ACE) produced by vascular endothelial cells in the lung
- Release of Aldosterone in response to Angiotensin II: Zona glomerulosa in adrenal cortex
[UpToDate: The classical (historical) view of the renin-angiotensin system (RAS) pathway begins with renin cleaving its substrate, angiotensinogen (AGT), to produce the inactive peptide, angiotensin I, which is then converted to angiotensin II by endothelial angiotensin-converting enzyme (ACE). ACE activation of angiotensin II occurs most extensively in the lung. Angiotensin II mediates vasoconstriction as well as aldosterone release from the adrenal gland, resulting in sodium retention and increased blood pressure.
However, it is widely recognized that this classical view of the endocrine RAS pathway represents an incomplete description of the system. Instead of one simple circulating RAS, it is recognized that there are also several tissue (local) renin-angiotensin systems that function independently of each other and of the circulating RAS. In particular, angiotensin II generation at the tissue level by these local systems appears to have physiologic effects that are as important as circulating angiotensin II and, under some circumstances, more important than circulating angiotensin II.
Thus, the RAS includes local systems with autocrine (cell-to-same cell) and paracrine (cell-to-different cell) effects in addition to the classical circulating RAS with endocrine effects. Physiology of the RAS is proving far more complex than a simple circulating pathway controlling blood volume and blood pressure. In these local systems, activation of angiotensin II results in harmful effects and target-organ damage that extend beyond vascular and renal hemodynamics to direct tissue actions, including tissue remodeling, endothelial dysfunction, and fibrosis. A more detailed review appears below.
A teleological view holds that activation of the RAS was a critical adaptation for survival of mammals that migrated from sea to land, in defense against life-threatening circumstances like salt and water deprivation, diarrhea, or hemorrhage. While protective in its purpose, activation of the system in many patients today is maladaptive and leads to disease, with heart failure being a classic example. Sodium retention, coupled with hyperaldosteronism, results in vascular remodeling of the heart and disease progression.
Blockade of the RAS has represented a groundbreaking development in the prevention and treatment of heart failure, chronic kidney disease, myocardial infarction, and hypertension. There are a number of steps at which the RAS can be interrupted. Beta-adrenergic blocking agents reduce renin release. ACE inhibitors block the conversion of angiotensin I to angiotensin II downstream from the renin step, and angiotensin receptor blockers (ARBs) interfere with the interaction of the angiotensin II with its receptor. A newer class of antihypertensive drugs, renin inhibitors, interfere with the first step in the cascade, which is the interaction of renin with its substrate, angiotensinogen.
Whether or not to block the RAS is no longer the appropriate question in the clinical scenarios of diabetic nephropathy, chronic kidney disease, and heart failure. Efforts are dedicated to answering how best to optimize blockade. Discoveries of new peptides, enzymes, receptors, and cell-signaling targets of the system are changing our understanding of physiology and providing potential new therapeutic targets.]
What physiologic effects does angiotensin II have?
- Vasoconstriction
- Increased heart rate
- Increased heart contractility
- Glycogenolysis
- Gluconeogenesis
- Inhibition of renin release
[UpToDate: The classical systemic effects of angiotensin II include:
- Vasoconstriction – Angiotensin II produces arteriolar vasoconstriction, which increases systemic vascular resistance and, therefore, systemic blood pressure.
- Reabsorption of sodium and water – Angiotensin II stimulates sodium reabsorption directly in the proximal tubule, and indirectly in the cortical collecting tubule by inducing secretion of aldosterone by the adrenal cortex.
Both of these actions tend to reverse the hypotension or hypovolemia that is usually responsible for the stimulation of renin secretion. In addition to influencing systemic hemodynamics, angiotensin II has an important role in the regulation of glomerular filtration rate (GFR) and renal blood flow. Angiotensin II produces vasoconstriction of the efferent and afferent glomerular arterioles as well as the interlobular artery. The net effect is a reduction in renal blood flow (due to the increase in renal vascular resistance) and an elevation in the hydraulic pressure in the glomerular capillary, which tends to maintain the GFR when the RAS is activated by a fall in systemic pressure.
Beyond these effects, however, angiotensin II has a host of important and mostly deleterious actions, as examples:
- Angiotensin II acts as an inflammatory mediator through a variety of mechanisms, including intercellular and vascular adhesion molecules (ICAM and VCAM), reactive oxygen species, nuclear factor-kB, and superoxide, exerting a proinflammatory effect on leukocytes, endothelial cells, and vascular smooth-muscle cells.
- Angiotensin II also provides a mitogenic stimulus for vascular smooth-muscle cells and promotes cellular proliferation, which could contribute to atherogenesis, and may also contribute to insulin resistance.
The effects of angiotensin II are mediated by binding to two specific angiotensin II receptors: the angiotensin II type 1 receptor (AT1R) and the angiotensin II type 2 receptor (AT2R). The vast majority of its actions, including the classical effects and many deleterious effects including fibrosis and inflammation, are mediated by the AT1R. AT2Rs are more sparsely expressed but can be upregulated in response to injury; effects of angiotensin II binding to the AT2R generally counteract its classical actions, producing vasodilation and natriuresis and possibly protecting against hypertension target-organ damage.]
Which conditions or factors increase dead space?
- Decreased cardiac output
- Pulmonary embolism
- Pulmonary hypertension
- Acute respiratory distress syndrome (ARDS)
- Excessive PEEP
[Can lead to high CO2 buildup (hypercapnia).]
By what mechanism does aldosterone affect homeostasis?
Promotes reabsorption of water at the distal convoluted tubule by upregulating the Na/K ATPase on the membrane (More Na re-absorbed and K secreted)
[UpToDate: Aldosterone binds to the mineralocorticoid receptor in various tissues, inducing pleiotropic effects. Its main action is in the kidney, where it increases the expression of epithelial sodium channels in the distal tubule, resulting in sodium and water reabsorption and potassium secretion. These renal actions contribute to extracellular fluid volume expansion, increased blood pressure, decreased serum potassium, and, when aldosterone is produced in excess, the primary aldosteronism. The hypokalemia that marks this syndrome results from aldosterone increasing potassium excretion in urine, feces, sweat, and saliva.]
Which immune cells are the primary mediators of acute respiratory distress syndrome (ARDS)?
Polymorphonucleocytes (PMNs)
[Increased proteinaceous material leads to increased A-a gradient, and increased pulmonary shunt.]
[UpToDate: Acute respiratory distress syndrome (ARDS) is a consequence of an alveolar injury producing diffuse alveolar damage. The injury causes release of pro-inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-8. These cytokines recruit neutrophils to the lungs, where they become activated and release toxic mediators (eg, reactive oxygen species and proteases) that damage the capillary endothelium and alveolar epithelium.
Damage to the capillary endothelium allows protein to escape from the vascular space. The oncotic gradient that favors resorption of fluid is lost and fluid pours into the interstitium, overwhelming the lymphatics. The ability to upregulate alveolar fluid clearance may also be lost. Increase in interstitial fluid, combined with damage to the alveolar epithelium, causes the air spaces to fill with bloody, proteinaceous edema fluid and debris from degenerating cells. In addition, functional surfactant is lost, resulting in alveolar collapse.
Lung injury has numerous consequences including impairment of gas exchange, decreased lung compliance, and increased pulmonary arterial pressure.
Impaired gas exchange – Impaired gas exchange in ARDS is primarily due to ventilation-perfusion mismatching: physiologic shunting causes hypoxemia, while increased physiologic dead space impairs carbon dioxide elimination. A high minute volume is generally needed to maintain a normal arterial carbon dioxide tension (PaCO2), although hypercapnia is uncommon.
Decreased lung compliance – Decreased pulmonary compliance is one of the hallmarks of ARDS. It is a consequence of the stiffness of poorly or nonaerated lung, rather than the pressure-volume characteristics of residual functioning lung units. Even small tidal volumes can exceed the lung’s inspiratory capacity and cause a dramatic rise in airway pressures.
Pulmonary hypertension – Pulmonary hypertension (PH) occurs in up to 25% of patients with ARDS who undergo mechanical ventilation. Causes include hypoxic vasoconstriction, vascular compression by positive airway pressure, parenchymal destruction, airway collapse, hypercarbia, and pulmonary vasoconstrictors. The clinical importance of PH in most patients with ARDS is uncertain. PH severe enough to induce cor pulmonale is rare, but it is associated with an increased risk of death.]
A right shift on the oxygen-hgb dissociation curve is caused by increasing or a decreasing the following factors:
- CO2
- pH
- temperature
- ATP production
- 2,3-DPG production
- Increased CO2
- Decreased pH
- Increased temperature
- Increased ATP production
- Increased 2,3-DPG production
[Opposite of above causes a left shift (increased O2 binding.]
How do the below pulmonary characteristics change in restrictive lung disease?
- Total lung capacity (TLC):
- Residual volume (RV):
- Forced vital capacity (FVC):
- Forced expiratory volume (FEV1):
- Total lung capacity (TLC): Decreased
- Residual volume (RV): Decreased
- Forced vital capacity (FVC): Decreased
- Forced expiratory volume (FEV1): Normal or Increased
Dead space is the area of the lung that is ventilated but not perfused which anatomically extends to where in the lung?
The level of the bronchioles (150mL usually)
