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Chalk Talk 2

Posted on July 17, 2017 by Yilin Zhang

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Chalk Talk 2

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CHALK TALKS (20-30min)

  • Cardiology
    • Wide Complex Tachycardia
    • Shock and Vasopressors
    • Diagnosing STEMI – Coronary Distribution
    • Pericarditis
    • Code Blue
    • Cardiopulmonary US – CLUE
  • Endocrinology
    • Adrenal Insufficiency
  • Gastroenterology
    • Inpatient Management of Cirrhosis
    • AKI in Cirrhosis (Hepatorenal Syndrome)
    • Gallstone Disease
    • Liver Abscesses
  • Hematology
    • Venous Thromboembolism (VTE) – Initial Management
    • Transfusion Reactions
  • Infectious Disease
    • Inpatient Abx, Part 1: Spectrum
    • Inpatient Abx, Part 2: Common Sites
  • Nephrology
    • Hyponatremia – 3 Lab Approach to Diagnosis
    • Pathophysiology, Diagnosis and Management of Hyponatremia
    • AKI in Cirrhosis (Hepatorenal Syndrome)
  • Pulmonology
    • Venous Thromboembolism (VTE) – Initial Management
    • Oxygen Delivery Devices
    • Inpatient Evaluation of Hypoxia
    • Pulmonary Hypertension
  • Rheumatology
    • Purple Fingers and Toes
  • Transplant Medicine
    • Solid Organ Transplant Medicine

CASES (20-30min)

  • Cardiology
    • GCA aortitis with pericardial effusion
    • STEMI
    • IVDU-related Infective Endocarditis
    • Amiodarone induced thyrotoxicosis with warfarin toxicity (AICDs)
  • Dermatology
    • Streptococcal Toxic Shock Syndrome
    • DRESS Syndrome
    • Pemphigus Vulgaris (Case 2)
    • ATG-related Serum Sickness
    • Acute Granulomatosis Polyangiitis
    • Drug induced Eosinophilic Pneumonia
  • Endocrinology
    • Secondary Adrenal Insufficiency
    • Amiodarone induced thyrotoxicosis with warfarin toxicity
    • Licorice (glycyrrhizic acid) Induced Pseudohyperaldosteronism
  • GI
    • Case Series on Esophagitis
    • Boerhaave’s syndrome
    • Klebsiella Liver Abscess
    • Peripancreatic fluid collection
    • IBD Flare
  • Hematology
    • Thrombotic Thrombocytopenic Purpura
    • AML with Pulmonary Leukostasis
    • TCA Induced Agranulocytosis
    • Immune Thrombocytopenia
    • TRALI and Other Transfusion Reactions
    • Peripheral eosinophilia (Drug Induce Eosinphilic Pneumonia)
    • Heinz-body hemolysis (Methemolgobinemia)
  • Immunology
    • ATG-related Serum Sickness
    • DRESS Syndrome
    • Immune Thrombocytopenia
    • Drug induced Eosinophilic Pneumonia
  • ID
    • Candida Esophagitis (Case 1)
    • Hypoxia Post Lung Transplantation
    • Streptococcal Toxic Shock Syndrome
    • IVDU-related Infective Endocarditis
    • Septic Pulmonary Emboli (MRSA Bacteremia)
    • Klebsiella Liver Abscess
    • Typhoid Fever
  • Nephrology
    • AKI Post Kidney Transplantation
    • Hyponatremia (1)
    • Hyponatremia (2)
  • Pulmonary
    • Incidentally Discovered Pulmonary Hypertension (Clinic Series)
    • Diffuse Alveolar Hemorrhage
    • Hypoxia Post Lung Transplantation
    • Cystic Lung Disease
    • AML with Pulmonary Leukostasis
    • Septic Pulmonary Emboli and MRSA Bacteremia
    • Case Series on Hypoxia
    • TRALI and Other Transfusion Reactions
    • Drug induced Eosinophilic Pneumonia
    • Non-resolving Pneumonia
    • Amiodarone Pulmonary Toxicity
    • Granulomatosis with polyangiitis (pulmonary nodule)
    • Bloody Pleural Effusion
    • Dapsone-induced Methemoglobinemia
  • Rheumatology
    • Granulomatosis polyangiitis
    • GCA aortitis and pericardial effusion
  • Transplant Medicine
    • Hypoxia Post Lung Transplantation
    • AKI Post Kidney Transplantation
    • ATG-related Serum Sickness
    • Hyponatremia

CLINICAL IMAGES (5min)

  • Chest
    • Opacified hemithorax
    • Biatrial Enlargement
    • Nonresolving pneumonia
    • Tuberculous aortitis
    • Excipient lung
    • Obstructing mediastinal mass with volume loss
    • Cannon ball lesions
    • Chronic eosinophilic pneumonia
    • Mediastinal lymphoma with pleural effusion
    • Fat embolism syndrome
    • Trapped Lung
    • Amiodarone Pulmonary Toxicity
  • Abdominal
    • Gastric Outlet Obstruction
  • ECGs
    • Rate Related Bundle Branch Blocks
  • Hematology
    • Schistocytes
  • Licensing

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    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
  • Disclaimer

    Patient confidentiality is a priority.  No case presented here contains uniquely identifying characteristics, nor do the cases reflect the presentation or care of any one individual.  Rather, they represent a compilation of similar cases adapted to achieve the greatest educational value and generalizability.

    The authors pro­vide this content for infor­ma­tional pur­poses only. This content is not intended, nor should it be used as medical advice.

    The content on this site does not necessarily represent the opinions of the principal author, team or their employer.

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Sarcoidosis

Non-caseating granulomatous disease that effects multiple systems.  It effects all races (African-American > Caucasians > Asians) and sexes everywhere in the world usually ages 20 to 50 years old with familial clustering. 

Defining characteristics
At least 90% with diffuse nodular pulmonary disease and/or hilar lymphadenopathy
Diffuse nodular lung disease
Cardiac and ocular involvement
ACE enzyme elevated in 70%
Steroid responsive

Courtesy of Lauren Brown, MD
Right Heart Catheterization

A RHC provides important hemodynamic measurements of:

  • RA and RV pressures 
  • PA pressures 
  • PCWP, also known as pulmonary arterial occlusion pressure (PAOP)
  • Cardiac output 
  • PVR and systemic vascular resistance (calculated)

These measurements are important for assessment of the severity of PH and underlying etiology, in particular, differentiating Group 1 and Group 2 PH. 

WHO Classification of PH

  1. Pulmonary arterial hypertension (PAH) (1’s look like a vessel) – vasculopathy affecting small pulmonary arterioles
    • Can be associated with connective tissue diseases such as SLE, RA, systemic sclerosis
    • HIV infection – mechanism is unclear, CD4 count independent, but correlates with duration of infection
    • Drugs/ toxins – anorexigens, methamphetamine, cocaine
  2. PH from LH disease (2’s look like a heart) – initially occurs as pulmonary venous hypertension but with time pulmonary arterial hypertension can occur as an adaptive mechanism
  3. PH from lung disease and chronic hypoxia (3’s look like lungs)
    • COPD – PH is typically mild
    • ILD – PH is common, up to 40% of patients
    • OSA/OHS – PH results from chronic hypoxia
  4. Chronic thromboembolic PH (4’s look like legs, invoke DVTs) – multiple organizing thromboemboli in pulmonary arteries results in ↑ resistance and pressures
  5. Miscellaneous – this group includes a mix of diseases that don’t clearly fit into other categories. Of note, there are frequently overlap with other groups (e.g., thyroid and metabolic disorders also can cause group 1 PAH)
Median Survival by Functional Class

NYHA Functional Class Median survival
I and II 6.5 yrs
III 2.8 yrs
IV 6 months

Original data from an NIH registry of 194 patients diagnosed with IPAH.1 

Work-up of Pulmonary Hypertension

  • PFTs (spirometry, lung volumes, DLCO
  • Labs:
    • Drug screen for methamphetamine use (Group 1 PH)
    • ANA +reflexive panel (Group 1 PH). Consider anti-SSA and SCL70, ANCA and other autoimmune serologies in patients with risk factors.
    • CMP, HCV screen for portopulmonary hypertension (Group 1 PH)
    • HIV screen for HIV associated PAH (Group 1 PH)
    • TSH and free T4 (Group 5 PH)
    • CBC,  iron panel
    • Evaluation for schistosomiasis if appropriate history (Group 1 PH)
    • BNP
  • V/Q scan > CTA for screening for CTEPH (Group 4 PH).
    • Only 1/2 of patients with CTEPH report symptoms of acute PE.
    • A CTA chest or pulmonary angiography should follow a high probability V/Q scan.
  • Consider a high-resolution CT scan (ILD protocol) (Group 3 PH)
  • Consider a sleep study (Group 3 PH). Sleep disordered breathing is common in all forms of heart failure and should never be given credit for a PASP > 55 mmHg in the absence of another contributing cause of PH.
TTE Estimation of Pulmonary Pressures

TTE estimates pulmonary pressures in a number of different ways. Most commonly, PASP is calculated from the peak tricuspid regurgitant (TR) jet velocity using the modified Bernoulli equation:3 

PASP = 4*(TRmax)2 + RA-P
mPAP is estimated from PASP by 0.61*PASP + 2 mmHg

This estimate is dependent on the correct alignment of the Doppler along the TR jet and an accurate estimate of the right atrial pressure (RA-P). For this reason, a TTE can either under or overestimate the PASP. 

  • Ten to 25% of patients with PH have insufficient TR jet.1 A contrast-enhanced TTE (with IV agitated saline) can augment TR signal in some of these patients.1,2
  • TR jet is underestimated in patients with compensated RV (which leads to underestimation of PASP and thus, mPAP).2
  • Severe TR can result in underestimation of PASP.2 
  • RA pressure (RA-P), which also factors into PASP calculation, is often overestimated by inferior vena cava measurement, which can lead to overestimation of PASP.2

There are several other ways to calculate pulmonary pressures, including direct estimation of mPAP that involve assessment of the pulmonary regurgitant jet.2 Each method has some limitations. Definitive diagnosis of PH requires RHC. 

Non-anion gap metabolic acidosis

Non-AG metabolic acidosis (NAGMA) results from HCO3 losses from the GI tract or kidneys. A urinary anion gap (UAG = UNa + UK – UCl) , essentially calculates urinary HCO3. A positive UAG indicates urinary loss of HCO3 (excess NS administration, RTA, renal failure). A negative (negGUTive) UAG indicates GI losses such as diarrhea, ileostomies, neobladders, fistulas.

Respiratory compensation typically occurs in hours. Formal calculation for the expected compensation is Winter’s formula: expected pCO2 = (1.5 x HCO3-) + 8  ± 2. However, a shortcut can be used for acute metabolic acidosis – the expected pCO2 is roughly the 2 digits of the pH (digits after the period). 

Anion gap metabolic acidosis

Teaching Instructions: You may replicate this on a white board by drawing in the diagram as you walk through it. 

After identifying a metabolic acidosis, calculate whether there is an ↑ anion gap (AG) (Step 3). Normal AG is Na – (HCO3 + Cl) and is ~ 8-12, however, is dependent on albumin. Because the uncalculated anions are predominantly albumin, patients with hypoalbuminemia have lower expected AGs. Thus, an AG of 12 may be elevated in a patient with low albumin.


The differential of AG metabolic acidosis (AGMA) is captured in the mneumonic MUDPILES. Other causes include cyanide or CO poisoning, meds (iron, zidovudine), rhabdomyolysis. Of note, toxic alcohols – methanol and ethylene glycol – will cause both an osmolar gap and elevated AG. 

Patients with an AGMA should be evaluated for anothe concurrent metabolic process by calculating the delta-delta (ΔΔ) or our preferred method, the “residual HCO3“. Calculate the ΔAG and add this back to the measured HCO3, essentially accounting for the AGMA. If this residual HCO3 is normal (22-26), there is a pure AG because accounting for the AG fully corrected the metabolic process. If the residual HCO3 is low (>22), this indicates another metabolic acidosis is present even after accounting for the AGMA. Thus, there is a concurrent AGMA and NAGMA. 

Treatment of Shock

Teaching Instructions: Have your learners synthesize all the information they learned and apply it to the treatment of the different types of shock. 

  • Hypovolemic: Aggressive volume resuscitation is key. Rapid volume expansion is best done through 2 large bore (bigger than 14G or 16G) IVs or through a Cordis/ introducer. Vasopressors that further ↑ SVR are unlikely to have a significant impact if the “tank isn’t full.”
  • Cardiogenic: Inotropes, such as dobutamine, are the cornerstone of treatment for cardiogenic shock. Dobutamine  ↑ CO by ↑HR and cardiac contractility. Dobutamine also mildly ↓ SVR, which further improves forward flow. Isoproterenol has significant β2 (chronotropic) activity and is particularly effective in cardiogenic shock from bradyarrhythmias. Dopamine (DA), norepinephrine (NE) and epinephrine (epi) also have some inotropic effects and can be used as second line in cardiogenic shock. Diuresis is also important in cardiogenic shock 2/2 to ↓ LV function to restore cardiac myocytes on the Starling curve.
  • Obstructive: Treatment is directed at the underlying cause (e.g. decompression of PTX, drainage of pericardial effusion, anticoagulation or thrombolysis for  PE). Inotropes can be helpful to improve cardiac contractility. 
  • Distributive: 
    • Sepsis3 – NE is first line. Vasopressin and epi can be added to NE as second line agents. DA can be used in patients who are relatively bradycardic. Dobutamine can be considered in patients who are hypotensive despite IVF and vasopressor support. IVF and antibiotics are also important in management of septic shock.
    • Anaphylactic – Epinephrine is vasopressor of choice (because of its β2 activity which causes bronchodilation).
Vasopressors and Inotropes (detailed)

Pathophysiology of Vasopressors

Teaching instructions: Start by discussing the role of different receptors on the heart diagram. Remind your learners that this diagram is a very simplified version of complex physiology. 

  • α1: vascular smooth muscle (s.m.) → peripheral vasoconstriction
  • β1: cardiac myocytes, pacemaker cells in sinoatrial and atrioventricular nodes → ↑ HR, contractility
  • β2: bronchial s.m., vascular s.m. → bronchodilation, vasodilation
  • V1 (vasopressin): vascular s.m. → vasoconstriction
  • V2: renal collecting tubules → ↑ free water resorption
  • D1/2 (dopamine): renal vasculatures → ↑ renal blood flow

Next, go through the commonly used inotropes and vasopressors – draw their pictorally on the “pressor spedometer” and have your learners predict its hemodynamic effect.  You may electively ask your learners to choose which types of shock these vasopressors would be most effective at treating.

Types of Shock - Expanded Table

Types of Shock

Teaching Instructions: After discussing the pathophysiology of shock, engage your learners to identify 4 primary categories of shock: hypovolemic, cardiogenic, obstructive and distributive. Challenge your learners to list different causes within each category of shock and the impact on CVP/preload, CO and SVR. Start by identifying the primary problem in each type of shock (e.g., ↓ preload in hypovolemic shock, ↓ CO in cardiogenic shock).

  • Hypovolemic: GI losses (vomiting, diarrhea), overdiuresis, hemorrhage
    • Primary ↓↓ preload. While there is a compensatory ↑ contractility initially to try to maintain CO, after 20% volume loss, these mechanisms fail and CO ↓ because preload (and thus, SV) ↓.1 SVR ↑ to preserve perfusion to vital organs.
  • Cardiogenic: systolic or diastolic dysfunction, MI, arrhythmias, anatomic defects (e.g., VSDs), valvular dysfunction
    • Primary ↓↓ CO (or in some cases such as severe MR, by ↓↓ forward CO). A ↓ in forward flow → ↑ CVP,  ↑ SVR. 
    • MIs that result in cardiogenic shock typically involve the L main or LAD distributions and affect > 40% of the myocardium.1
  • Obstructive: 
    • Obstruction in any portion of the cardiovascular circuit → ↓ in forward CO. 
      • Inflow to RH – tension PTX, mediastinal tumors
      • Outflow from RH – massive PE
      • Inflow to LH – tamponade, constrictive pericarditis
    • There is compensatory ↑ SVR. CVP is typically ↑ (but may be ↓ with tension PTX).
  • Distributive:
    • Primary loss of (↓)  SVR.
      • Injury to sympathetic nervous system –  neurogenic
      • Deficiency in vasoactive substances – adrenal crisis
      • Release of vasodilatory substances – sepsis, anaphylaxis
    • There is compensatory ↑ CO for ↓ SVR. CVP is typically normal or ↓ from peripheral pooling of blood → ↓ venous return.
Pathophysiology of Shock

Teaching Instructions: Start by introducing the concept of shock and its determinants (cardiac output or CO, venous return, systemic vascular resistance or SVR). While discussing this portion, fill in the heart diagram. 

Shock is a syndrome of circulatory  failure that results in cellular hypoxia and organ dysfunction. Clinically, shock manifests as hypotension with signs of end organ damage. There are 3 predominant  determinants of shock:

  1. Cardiac output (CO, aka “pump function”): Determined by HR x stroke volume (SV). SV is determined by preload, afterload and contractility. 
  2. Venous return (“how full the tank is”): Central venous pressure (CVP) is one marker of venous return. On physical exam, jugular venous pulsations (JVP) is a surrogate for CVP. 
  3. Systemic vascular resistance (SVR): Determines the distribution of cardiac output. On physican exam, patients with ↑ SVR will have “cold and clammy extremities” while those with ↓ SVR  will have “warm extremities”.
Laboratory evaluation

  • Infectious:
    • Respiratory viral panel – negative
    • Serum galactomannan (for Aspergillus) – negative
    • Serum cocciomycosis antibody – negative
    • Strongyloides antibody – negative
    • HIV – negative
    • HBV and HCV serology – negative
    • quantiferon TB – negative
  • Inflammatory:
    • ANA – negative
    • ANCA – negative
    • Rheumatoid factor and anti-CCP – negative
    • Anti-GBM antibody – negative
CT scan


CT shows diffuse ground-glass opacities in both lungs that partially spare the lung bases and periphery. Some areas show superimposed interlobular/septal lines, which is a finding called “crazy paving”

CT scan

CT chest

Risk Stratefying and Management of TLS

Laboratory Results

  • LDH elevated at 450 (elevated)
  • Haptoglobin < 30 (low)
  • Peripheral smear showed evidence of Heinz bodies, fragmented RBCs

  • Coags were normal
TACO versus TRALI

Intraabdominal Infections

  • Intraabdominal infections include biliary and bowel infections
  • Most common pathogens include enteric streptococcal species, GNRs and anaerobes (in particular Bacteroides)
  • Empiric coverage should include coverage of Strep, GNRs and anaerobes
    • Mild community acquired cholecystitis can be managed without anaerobic coverage 12
    • There is increasing resistance of E. coli to Unasyn and FQs12
NSTI

  • Infections can be monomicrobial or polymicrobial
    • Staph and Strep are implicated in vast majority of cases (in one study, ~80% of cases)10
    • GNRs include Enterobacteriaceae and Pseudomonas in polymicrobial infections10, Vibro and Aeromonas can cause monomicrobial NSTI9
    • Anaerobes include Clostridium, Bacteroides and Peptostreptococcus10
  • Daptomycin and linezolid are alternatives to Vancomycin for MRSA coverage
  • Carbapenems, Zosyn and FQ or ceftriaxone + metronidazole are options for GN coverage
  • “Quad therapy” with Vancomycin, pencillin, levofloxacin and clindamycin is used at some institutions for NSTI (the penicillin and clindamycin are specifically for NSTI 2/2 to GAS)
    • Clindamycin should be included in patients with NSTI suspected 2/2 to GAS (decreases toxin production)
  • Patient’s with suspected NSTI should have a surgical consult
Purulent SSTI

  • Treatment should include I&D of any drainable absceses
  • Antibiotic coverage should cover MRSA 
    • Parenteral options – Vancomycin, daptomycin or linezolid
    • Oral options – Bactrim, clindamycin, doxycycline depending on local resistance rates
  • If oral Bactrim or doxycycline are used, strongly consider additional coverage for Strep (e.g. cephalexin)
Non-purulent SSTI

  • Nonpurulent cellulitis is most commonly caused by streptococcal species (often Group A Strep)9
  • S. aureus cellulitis is more commonly associated with IVDU, open wounds, trauma9
  • MRSA is a rarely a cause of non-purulent SSTIs9
  • Treatment duration is 5 d if clinical improvement is seen by then
UTI

Uncomplicated cystitis/ pyelonephritis: “PESK” 

  • E. coli accounts for 75 – 95% of all cases > S. saprophyticu, Enterbacterieaceae (Klebsiella, Proteus)6
  • Nitrofurantoin, Bactrim and fosfomycin are 1st line for uncomplicated UTI
    • Avoid nitrofurantoin and fosphamycin in suspected pyelonephritis
  • ↑ E. coli resistance to urinary FQ (cipro/levo)

Catheter-associated UTIs: “SEEKS PP” for CAUTIs

  • UTI in a patient with a catheter or has been catheterized within 48h
  • E. coli is most common (27%), followed by Enterobacteriaceae [Klebsiella (11%), Proteus (5%) and Serratia (1%)] and Enterococcus (15%, faecalis > faecium), Pseudomonas (11%) and GPCs (S. saprophyticus and aureus, ~5%)8
  • Empiric coverage of GNRs is most important though adding Pseudomonal or ESBL coverage can be considered when there is high suspicion or for patients who are ill (antibiotics highlighted in red have Pseudomonal coverage)
Aspiration Pneumonia

  • Microbiology includes typical colonizers of the upper respiratory and GI tract – GPs, enteric GNRs and oral anaerobes (Peptostreptococcus, Peptococcus, Prevotella, Fusobacterium) 2,4,5.
  • Anaerobes are less commonly implicated in acute aspiration syndromes, but common cause patient patients with anaerobic pleural pulmonary syndrome2,4
  • Most empiric regimens should include GNR and anaerobic coverage, though clindamycin monotherapy was shown in one study to be noninferior to carbapenem or Unasyn5. 
HAP

  • HAP occurs >48 h after admission
  • Higher risk for MDR organisms including MRSA, Pseudomonas and MDR GNRs. Especially if antibiotic use within past 90 d3.
  • Of note, patients with frequent health care contacts that were previously classified under “health care associated pneumonia” are no longer thought to be at high risk for MDR pathogens3
  • Duration of therapy is 7 d
CAP

  • Most commonly caused by S. pneumoniae, atypical organisms and respiratory viruses2
  • GNRs (mostly H. flu and Moraxella) are important causes of CAP  in patients with underlying lung disease2
  • Higher level learning points
    • S. aureus pneumonia is a common cause of CAP during flu season2
    • Enterobactereaece and P. aeruginosa can cause CAP in patients on chronic oral steroids, underlying bronchopulmonary disease or alcoholism2
  • A beta-lactam + azithromycin or a respiratory FQ (levofloxacin/ moxifloxacin) are recommended empiric regimens2
  • Doxycycline can be a substitute for azithromycin for atypical coverage2
  • Duration of treatment is 5-7 d
Treatment

Primary adrenal insufficiency: Both mineralocorticoid (aldosterone) and glucocorticoid replacement needed. Additionally, adrenal androgen repletion is also needed. 

Glucocorticoid Hydrocortisone 20 – 25 mg/ 24 hr in two or three divided doses

>2/3 total daily dose given in the early morning to reflect natural pulsatile nature of cortisol secretion

Mineralocorticoid Fludrocortisone 100 μg daily
Androgen DHEA 25 – 50 mg daily

Central adrenal insufficiency: Only glucocorticoid replacement is needed (and typically at lower doses). Hydrocortisone 10 – 15 mg/24 h.

Diagnosis of AI

Rule of “3’s”

Cortisol secretion is pulsatile and peaks in the early morning (around 6 – 8 am). An AM cortisol > 15  mg/dL (or for even greater positive predictive value, > 18 mg/dL) is suggestive of AI. An AM cortisol < 3 mg/dL is strongly suggestive against AI.

The most commonly used test for inpatient diagnosis of AI is the cosyntropin stimulation test. A baseline cortisol level is measured at time 0 → 250 μg cosyntropin (essentially ACTH) given at time 0 → cortisol level is measured at 60 min. A cortisol level at 60 min < 18 mg/dL is suggestive of adrenal insufficiency. 

Tertiary AI

Pathophysiology: An insult at the level of the hypothalamus results in decreased CRH production and subseqeuntly ACTH and cortisol. The RAA axis and aldosterone production is preserved.

↓ CRH, ACTH and cortisol
RAA function preserved

Causes2: 

  • HPA suppression from long term glucocorticoid use is most common cause
  • Drugs 
    • mifepristone increases tissue resistance to glucocorticoids
    • antipsychotics (chlorpromazine) and antidepressants (imipramine) inhibit glucocorticoid mediated gene expression
  • Tumors, trauma, surgery and irradiation (similar to secondary AI)
Secondary AI

Pathophysiology: An insult at the level of the pituitary results in decreased ACTH production and consequentially decreased cortisol production. The RAA axis remains intact and aldosterone secretion is not affected. Low cortisol and ACTH levels negatively feedback to stimulate the hypothalamus to release CRH. Other pituitary hormones may also be affected.

↓ ACTH and cortisol, ↑ CRH
RAA unaffected

Causes2:

  • Pituitary apoplexy/ hemorrhage (in the peripartum setting, this is called Sheehan’s syndrome)
  • Trauma
  • Tumors (adenoms, cysts, craniopharyngiomas, meningiomas), surgery or intra-cranial irradiation
  • Infections – TB, meninigitis, actinomycosis
  • Infiltrative processes – sarcoid, granulomatosis polyangiitis, hematomachrosis, lymphocytic hypophysitis
Primary AI

Pathophysiology: An insult at the level of adrenals results in loss of cortisol and aldosterone production (as well as androgen production, which we won’t focus on). Decreased cortisol production results in a negative feedback loop to the pituitary and hypothalamus to increase production of ACTH and CRH, respectively. Loss of aldosterone production results in sodium and water excretion which can result in profound hypovolemia. Hypovolemia stimulates renin secretion resulting in a high renin state.

↓ cortisol, ↑ ACTH and CRH
↓ aldosterone, ↑ renin

Causes2:

  • Most common cause is autoimmune adrenalitis (80-90% in developed countries)2. Forty percent of these cases are associated with autoimmune polyendocrinopathy syndrome.
  • Infections (TB, AIDS, histoplasmosis/cryptococcosis/coccidiomycosis, syphilis, trypanosomiasis)
  • Adrenal hemorrhage (in the setting of meningococcal sepsis, primary antiphospholipid syndrome, anticoagulant use)
  • Drug induced
    • azoles, etomidate inhibits synthesis of cortisol3
    • phenobarbitol, phenytoin, rifampicin induce P450 enzymes and increase cortisol metabolism
  • Congenital adrenal hyperplasia is an important cause of AI in children
Pathophysiology

Teaching Instructions: This pathophysiology figure will be central in to the first portion of the talk that reviews primary, secondary versus tertiary adrenal insufficiency (AI) and their causes. Keep this figure up and adjust the arrows to reflect primary, secondary or tetiary AI. 

HPA axis: The hypothalamus releases corticotropin releasing hormone (CRH) which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH acts on the adrenal cortex (zona fasciculata) to release cortisol. Cortisol has a number of broad reaching effects, but notably increases sensitivity to catecholamines (epinephrine, norepinephrine which are released from the adrenal medulla). 

RAA axis: Decreased renal blood flow is sensed by the juxtoglomerular cells in the kidney which promote the release of renin. Renin converts a precursor to angiotensin I, which is further converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II itself is a potent vasoconstrictor, but additionally stimulates release of aldosterone from the adrenal cortex (zona glomerulosa). Aldosterone in turn acts on the kidneys to reabsorb Na (and with it water) and excrete potassium.  

Decompensated Cirrhosis

Under the “3. Compensated?” section, fill in “no” and median survival as you’re talking about cirrhosis. Have your learners list off some complications of cirrhosis that define decompensation and fill out the sections of the “Acute Decompensation” table. 

Patients with decompensated cirrhosis have complications of cirrhosis including hepatic encephalopathy, spontaneous bacterial peritonitis (SBP), variceal bleeding, hepatocellular carcinoma, ascites or hepatorenal syndrome. Patients with decompensated cirrhosis have a mean survivial of < 2 years.  One study showed a median survival of < 6 months if patients had a Child-Pugh score > 12 or MELD score > 21.  These cut offs were even lower (Child-Pugh score > 10 or MELD score > 18) for patients who were hospitalized with complications of cirrhosis. 

Acute decompensation, which can occur in previously compensated or stably decompensated patients, is defined by an ↑ in MELD score or development of one of the complications of cirrhosis. 

Cholangitis

The diagnosis of cholangitis is largely driven by clinical signs and symptoms! Charcot’s triad of cholangitis was fever, jaundice and RUQ pain. Cholangitis should be suspected in patients with fever, laboratory signs of inflammation (e.g. elevated WBC) and jaundice or elevated LFTs. Presence of biliary dilation on imaging makes diagnosis of cholangitis definite.

Cholangitis is pus under pressure and should be relieved with an ERCP. In patients who cannot get an ERCP or an ERCP is not successful, a PTC (percutaneous transhepatic cholangiogram) can be placeed to both diagnose and remove stones in the bile ducts. 

Choledocholithiasis

  • Choledocholithiasis, or gallstones in the common bile duct, causes proximal dilation of the common bile duct and intrahepatic ducts and typically results in a cholestatic pattern of LFT elevation.
  • RUQ US can show presence of biliary dilation and occassionally an obstructing stone, but most cases require MRCP or ERCP.
  • Decision to pursue MRCP or ERCP depends on wehther patients are  high likelihood or intermediate likelihood of having choledocholithiasis. Likelihood is determined the number and strength of predictors for choledocholithiasis.
  • Patients with choledocholithiasis should receive cholecystectomy.
Very strong predictors Strong predictors Moderate predictors
  • CBD stone on US
  • Cholangitis
  • Tbili > 4
  • Dilated CBD on US > 6 mm
  • Tbili 1.8 – 4 
  • ↑ LFTs
  • Age > 55
  • Gallstone pancreatitis
Cholecystitis

Cholecystitis occurs when there is inflammation and possible infection in the gallbladder caused by obstruction of the cystic duct by a stone or sludge.

  • Diagnostic imaging that is most common used include ultrasound (US), CT or HIDA scan.
  • Ultrasound is readily accessible and has reasonably good sensitivity and specificity. Signs of cholecystitis include distneded gallbladder, gallbladder wall thickening and pericholecystic fluid.
  • CT scans are also used widely, but are generally considered inferior to ultrasonography because of the higher detection of gallstones on US. Sensitivity and specificity have not been widely studied or reported. 
  • HIDA scan is the most sensitive and specific diagnostic test. A radio-labeled substance is injected IV and concentrates in the biliary system. If the gallbladder is enhanced, there is no obstruction of the cystic duct.

Treatment is with antibiotics (which should cover enteric GNRs and intraabdominal anaerobes), even though not all cases are associated with bacteiral infection. Biliary drainge or removal is needed for definitive treatment. 

Cholelilithiasis

  • Asymptomatic gallstones should be managed expectantly.
  • Biliary colic occurs with intermittent obstruction of the cystic duct by gallstones or sludge.
  • Patients with symptomatic gallstones who are low surgical risk should undergo an elective (most commonly laparoscopic) cholecystectomy. 
  • Patients who do not want to undergo surgery or are high risk for surgery can receive oral dissolution therapy with medications like ursodeoxycholic acid (or ursodiol). Ursodiol is a bile acid that concentrates in the gallbladder and shifts the cholesterol-bile acid gallstone concentration, making gallstones more soluble. 
    • Works best for small, cholesterol rich stones without calcifications
    • Works slowly (takes months) and high recurrence (25% in 5 years)1
Biliary Anatomy

Briefly review biliary anatomy to give a framework for understanding biliary disease.

  • Right and left hepatic ducts, which drain bile from smaller intrahepatic bile ducts, combine to form the common hepatic duct. 
  • The gallbladder stores bile created by the liver and excretes it via the cystic duct.
  • The cystic duct and common hepatic duct combine to form the common bile duct.
  • The pancreatic duct connects with the common bile duct to form the ampulla of Vater which almost immediately drains into the second portion of the duodenum (where the ampulla actually enters the duodenum is called the papilla.
CT Interpretation

There is basilar predominant fibrosis without honeycombing with subpleural sparing in the posterior lung bases (fibrosis spares the area just adjacent to the pleura, this is not prominent in this particular CT). This pattern is consistent with NSIP (nonspecific interstitial pneumonia). NSIP (nonspecific interstitial pneumonia) is a histologic finding characterized by peripheral, peribronchovascular ground glass opacities with associated fibrosis. There is basilar predominance and subpleural sparing may be present.

Circled in green is the spleen which appears hyperdense.

Time to Radiographic Resolution

Risk Factors for Delayed Resolution

CT interpretation

CT additionally showed some small subcentimeter pulmonary nodules that are indeterminate.

Causes of Peripheral Eosinophilia

Results of laboratory work-up

  • Blood cultures, sputum culture, Strep and Legionella urinary antigen negative
  • B12 level normal
  • Stool O&P negative x 2
  • ANA and ANCA negative
  • Histomycosis and coccidiomycosis serology negative
  • HIV negative
  • Strongyloides serology negative
  • Total IgE level elevated at 1390, Aspergillus IgE also elevated at 1.9

Pulmonology was consulted and she underwent a bronchoscopy:

  • 79% eosinophils on her BAL fluid
  • Bacterial cultures negative
  • Aspergillus PCR negative, BAL galatomannan low 

Review of recent CT C/A/P without lymphadenopathy or splenomegaly. 

Management Options

Cystogastrotomy

cystogastrostomy

Johns Hopkins GI and Hepatology website: https://gi.jhsps.org/Upload/200802291654_10407_000.jpg

Nonsurgical Options for Pseudocyst Drainage

endoscopic and percutaneous
Clinical Gastroenterology and Hepatology Journal: http://www.cghjournal.org/cms/attachment/2006110911/2027664469/gr5.jpg

Primary Adrenal Insufficiency

In primary adrenal insuffiiciency, the insult is at the level of the adrenal glands so there is a decrease in both cortisol and aldosterone. It is the mineralocorticoid deficiency (aldosterone) that results in hypovolemia, which can result in profound shock.

HPA Axis Pathophysiology

ECG Interpretation

This rules out benign J point elevation as an explanation for the ST segment elevations seen on the first ECG.

ECG Interpretation

Accelerated idoventricular rhythm w/ L bundle morphology at a rate of 80 with occasional sinus beats.

ECG Interpretation

CT Interpretation

Findings suspicious for septic emboli or fungal infection.

SBP

Spontaneous bacterial peritonitis (SBP) occurs in up to 30% of patients with cirrhosis and ~ 10% of inpatients2. SBP occurs when enteric flora seeds and infects the ascitic fluid. Thus, the most common pathogens are enteric GNRs (E. coli, Klebsiella).  This is in contrast to secondary bacterial peritonitis (from gut perforation or secondary seeding from another intraabdominal infection) which often causes polymicrobial or fungal peritonitis. 

SBP can be subtle in presentation – essentially every patient admitted with cirrhosis and ascites should get a diagnostic paracentesis. SBP has a high in-hospital mortality of ~ 20%2. Early paracentesis within 12 hours of physician contact is associated with improved mortality. Each hour delay was associated with 3.3% increase in mortality1.

Presumptive SBP (ascitic PMNs > 250) is treated with a full course of IV antibiotics for 5 days. Albumin should be given to patients with advanced liver or renal failure (Cr > 1, BUN > 30, Tbili > 4), which has been shown to improve hospital mortality and ↓ risk of AKI2. 

Prophylaxis should be given to patients with a history of SBP, active GI bleeding, and anyone with advanced liver or renal disease who would have a poor outcome with development of SBP.

Varices and GI bleeding

Varices are dilated vessels that shunt blood around high pressure portal system. Esophageal varices are the most common cause of upper GI bleeding (UGIB) in patients with cirrhosis. Other portal hypertensive causes of UGIB include gastric varices and portal hypertensive gastropathy (PHG). 

Prevention: indicated in patients with moderate and large varices and small varices with severe liver disease

  • Non-selective beta-blockers 
    • Decreases portal pressures, target HR < 55
    • Should be discontinued in patients with refractory ascites, SBP or significant hypotension (SBP threshold of 90 or 100)1
  • Serial esophageal banding
  • TIPS 
Theoretical Mechanism of Lactulose

Hepatic Encephalopathy

Hepatic encephalopathy (HE) occurs in at least 30-40% of patients with cirrhosis2.  HE occurs because ↓ clearance of NH3 (produced by gut bacteria) by the liver → ↑ glutamine in brain cells → brain swelling.

HE is a clinical  diagnosis and ranges from ↓ attention to coma. Patients may have asterixis, hyperreflexia and very rarely focal neurologic deficits. Ammonia level is not a routine part of our work-up and is not needed for diagnosis (correlates with severity to a degree)2. Work-up should focus around evaluation of potential triggers:

  • Increased nitrogen load – sepsis/ infection, GI bleeding, increased protein intake
  • Decreased toxin clearance – hypovolemia, medication noncompliance/ constipation, TIPS
  • Sedating medications

Treatment:

  • Lactulose – omostic diarrhea decreases time for NH3 absorption, theoretically traps NH3 in the gut
  • Rifaximin – ↓ gut bacterial load and thus ↓ NH3 production
    • Lactulose and rifaximin combination therapy improves mortality and decreases hospitalization3
  • Use of polyethylene glycol (PEG) requires more study (small studies have shown non-inferiority to lactulose when 4L of PEG was given over 4 hours)4
AKI in Cirrhosis (HRS)

This provides a brief overview of AKI in cirrhosis and hepatorenal syndrome (HRS). More detailed chalk talk can be found here. The vast majority of AKI in cirrhosis is pre-renal (>60%) and is induced by volume depletion (overdiuresis), GI bleeding, sepsis or hepatorenal syndrome. The other component is largely made up of intrarenal causes (>30%) such as ATN. Work-up  should include routine work-up for AKI such as urinalysis and urine lytes. Since SBP is a common precipitant of both prerenal AKI and HRS, a diagnostic paracentesis should be performed in all patients. An albumin challenge helps differentiate between HRS and other pre-renal causes of AKI.

Hepatorenal syndrome is treated with:

  • albumin to expand plasma volume
  • midodrine and octreotide to decrease splanchnic vasodilation and raise peripheral BP (goal ↑ MAP > 15 mmHg)
  • diuretics and BP medications should be stopped 
  • TIPS can be considered in patients without advanced cirrhosis
  • Liver transplant is definitive therapy, dialysis is often used as a bridge to transplant
Ascites

Ascites is the most common complication of cirrhosis (and most patients with ascites have ascites because of liver disease). The evaluation of patients with new ascites should include a diagnostic paracentesis to evaluate for ascites albumin, ascites fluid total protein (AFTP) and serum albumin.

 New or worsening ascites from portal hypertensive causes should additionally prompt work-up with a RUQ US with duplex to rule out new portal system thrombosis. 

Management:

  • Sodium restricted diet (except for Na < 120)
  • Diuretics – furosemide/spironolactone at a ratio of 20/50 respectively

Refractory ascites occurs when patients do not respond to maximal doses of diuretics or cannot tolerate ↑ diuresis without compromise in renal function. These patients can be managed with serial large volume paracenteses and/or TIPS (addresses underlying portal hypertension). 

Overview of Cirrhosis

Set up the left side of your board as shown. The first part will discuss components of a “one-liner” or summary statement for patients with cirrhosis. You can give an example statement to help illustrate each part:

“60 M with decompensated alcoholic cirrhosis with a baseline MELD-Na of 23 complicated by a history of ascites and encephalopathy who presents with ___. “

  1. Causes of cirrhosis – causes are listed in order of prevalence. Generally, the causes of cirrhosis do not significantly impact how we manage the complications of their disease
  2. Compensated?
    • Compensated – no complications such as ascites, encephalopathy, variceal bleeding, hepatocellular carcinoma, etc. Patients are often asymptomatic for years and can leave for more than a decade.
    • Decompensated – poor median survival of 6 months8 – 2 yrs1. 
  3. MELD-Na score
    • Predicts 3 month mortality and is used for liver allocation
    • Relatively recently updated from MELD score – ↓ Na correlates with ↑ scores and poorer prognosis
  4. Any history of complications – we will explore the most common complications in the next section
Treatment Options for MRSA Bacteremia

Treatment of PH

Return to your table in section 2 of your board. 

General management principles applicable to all patients with pulmonary hypertension include:

  • Management of RH failure symptoms and volume overload – salt restriction, cautious diuresis (these patients are preload dependent!)
  • Oxygen to prevent further hypoxic vasoconstriction
    • Higher threshold for O2 initiation proposed for group 1 PH
    • Oxygen for PaO2 < 55 mmHg in group 3 PH has proven survival benefit

Anticoagulation is considered in group 1 and group 4 PH. Group 2 and 3 PH treatment is mostly directed at treating underlying disease. Advanced therapies vasodilate the pulmonary vasculature and are mostly for group 1 PH but occassionally are used in other groups. 

  • CCB – most commonly amlodipine, diltiazem, nifedipine. Use is guided by response to vasoreactivity testing during RHC. 
  • Further discussion of vasodilator therap#addlearnphies is included in the Additional Learning section.
Evaluation of Pulmonary Hypertension

Move back to section 1 of your board. Draw the flow diagram as you move through the work-up.

Anyone with suspected pulmonary hypertension should get a TTE, which will not only estimate pulmonary arterial pressures, but will evaluate for underlying LH disease that would suggest group 2 PH. 

Patients without significant LH dysfunction should undergo concurrent work-up for other causes of PH.

  • VQ scan (better than CT PE) → suggests group 4 PH 
  • PFTs → obstructive/restrictive lung disease → suggests group 3 PH
  • Overnight oximetry/ sleep study → group 3 PH
  • HIV, ANA, TSH, and LFTs (for portal hypertension) are initial first tests → group 1 and 5 PH

Anyone with suspected group 1 PH should receive RHC, which offers definitive diagnosis. Additionally able to measure/calculate PCWP pressure (↑ in group 2, low in other groups), PVR (> 3 Woods units in group 1 or PAH).

Groups of Pulmonary Hypertension

Move to section 2 of your board and fill in the table as your walk through each group of pulmonary hypertension. Pulmonary hypertension is divided into 5 general groups. To help remember them, we use the “number trick” – draw the group number and its reflection. 

  1. Pulmonary arterial hypertension (PAH) (1’s look like a vessel) – vasculopathy affecting small pulmonary arterioles
    • Can be associated with connective tissue diseases such as SLE, RA, systemic sclerosis
    • HIV infection – mechanism is unclear, CD4 count independent, but correlates with duration of infection
    • Drugs/ toxins – anorexigens, methamphetamine, cocaine
  2. PH from LH disease (2’s look like a heart) – initially occurs as pulmonary venous hypertension but with time pulmonary arterial hypertension can occur as an adaptive mechanism
  3. PH from lung disease and chronic hypoxia (3’s look like lungs)
    • COPD – PH is typically mild
    • ILD – PH is common, up to 40% of patients
    • OSA/OHS – PH results from chronic hypoxia
  4. Chronic thromboembolic PH (4’s look like legs, invoke DVTs) – multiple organizing thromboemboli in pulmonary arteries results in ↑ resistance and pressures
  5. Miscellaneous – this group includes a mix of diseases that don’t clearly fit into other categories. Of note, there are frequently overlap with other groups (e.g., thyroid and metabolic disorders also can cause group 1 PAH)
What is Pulmonary Hypertension?

Pulmonary hypertension occurs when the mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Normal systolic PAPs are 15 – 30 and diastolic PAPs are 5-10 with mean PAPs < 20 mMhg. 

Pulmonary hypertension ultimately leads to RV failure and will experience:

  • signs of RV overload – ↑ JVP, peripheral edema, hepatomegaly, ascites
  • exertional dyspnea, atypical chest pain
  • unexplained syncope
Simplified Pathophysiology

Other Antibiotics

  • Azithromycin – variable Strep coverage (high resistance), some GNs, good atypical coverage
  • Aztreonam – GN aerobes only, has Pseudomonal coverage
  • Aminoglycosides – GN coverage, has Pseudomonal coverage
  • Metronidazole – anaerobic coverage, C. diff coverage
Antibiotics That Cover MRSA

GP only antibiotics that cover MRSA:

  • Vancomycin – additionally covers Enterococcus though there is Vancomycin resistance (VRE)
  • Daptomycin – additionally covers VISA/VRSA and VRE. Cannot be used for MRSA pneumonia because it is inactivated by surfactant in the lungs
  • Linezolid – additionally covers VISA/VRSA and VRE.

PO antibiotics that cover MRSA:

  • Clindamycin – GP and anaerobic coverage. Variable activity against MRSA that is institution/region dependent (at our institution, currently ~ 40% resistance). Additionally ↓ toxin production. 
  • Bactrim – variable activity against MRSA that is institution/ region dependent, poor Strep coverage. 
  • Doxycycline – variable activity against MRSA that is institution/region dependent, poor Strep coverage. Has atypical coverage and is an alternative to azithromycin and FQs for patients with QTc prolongation.
Fluoroquinolones

Fluoroquinolones (FQs) are generally split into urinary and respiratory fluoroquinolones. 

Urinary FQs: Levofloxacin and ciprofloxacin achieve good concentrations in the urine. Moxifloxacin does not concentrate in the urine and is thus ineffective at treating UTIs. 

  • Ciprofloxacin – some MSSA coverage but poor Strep coverage, which is why it’s not used as a primary respiratory FQ. 
  • Levofloxacin – adds Strep coverage

Respiratory FQ: Ciprofloxacin is excluded because of its poor Strep coverage, but does reach the lungs in adequate concentrations. It is sometimes used for double  Pseudomonal coverage in CF patients. 

  • Levofloxacin – GP, GN, Pseudomonal and atypical coverage
  • Moxifloxacin – loses Pseudomonal coverage and adds better anaerobic coverage
Carbapenems

Carbapenems are extremely broad spectrum antibiotics that additionally have activity against extended spectrum beta-lactamases. 

General rule of thumb: no MRSA, no atypicals, poor Enterococcus

  • Ertapenem – GPs, GNs, anaerobic coverage but no Pseudomonal coverage. Benefit is that it is only dosed once daily. 
  • Meropenema/ Imipenem – added Pseudomonal coverage
Cephalosporins

There are 5 generations of cephalosporins. As we move through early generations to later generations, there is added gram negative coverage. 

General rules of thumb: no Enterococcus, no atypicals, no significant anaerobic coverage

  • 1st G (cephalexin, cefazolin) – great Staph and Strep coverage
  • 2nd G (cefofetin, cefuroxime) – some added GN coverage  (Enterobacteraceae, H. flu)
  • 3rd G
    • Ceftriaxone/ cefotaxime/ cefpodoxime – additional GN coverage 
    • Ceftazidime – poor GP coverage, but adds GN and Pseudomonal coverage
  • 4th G (cefepime) – GP, GN, and Pseudomonal coverage
  • 5th G (ceftaroline) – coverage of ceftriaxone + MRSA/ VISA/ VRSA coverage 
Pencillins

There are 3 broad classes of pencillins. As we move from early classes of pencillins to later classes, there is added gram negative and anaerobic coverage. 

General rules of thumb: no MRSA, no atypicals.

  • Pencillin – great Strep coverage (1st line therapy), high Staph resistance. 
  • Anti-staphylococcal pencillins (nafcillin) – great Staph and Strep coverage (1st line for MSSA)
  • Broad spectrum pencillins 
    • Unasyn or ampicillin-sulbactam – adds GN coverage, anaerobic coverage and some enterococcal coverage (predominantly E. faecalis)
    • Zosyn or piperacillin-tazobactam – Unasyn + Pseudomonal coverage

Fun Mneumonic for Enterococcus spp.

  • Enterococcus faecaLESS is LESS resistant (~90% ampicillin sensitive) and only rarely are Vancomycin resistant (aka VRE)
  • Enterococcus faecium is more resistant (~10% ampicillin sensitive) and more frequently is VRE
Treatment of HRS

The numbering corresponds to the discussed treatment option. 

The pathophysiology of HRS is critical in understanding the treatment options. 

  1. Stop BP lowering medications and diuretics! Hypotension and ↓ EAV contribute to AKI.
  2. Volume expand with albumin – these patients have ↓ EAV despite often being extravascularly overloaded. Give 25% albumin 1 g/kg x 48 h (max 100 mg/day) and subsequently give 20 – 40 g/day2. 
  3. Octreotide causes splanchnic vasoconstriction and can be dosed up 200 μg TID.
  4. Vasopressors counteract systemic vasodilation. On the floor, we most commonly use midodrine, which can be dosed up to 15 mg TID. Our goal is to increase MAP by > 15 mmHg.
  5. TIPS can be considered in patients without advanced cirrhosis.
  6. Liver transplant is the only definitive treatment option. Dialysis can be used as a bridge to transplant.
Diagnosis and Definition of HRS

Draw the “Diagnosis,” “Definition,” and “Treatment” headers. Fill in the rest of the chart, moving left to right as you walk through each section.

Diagnosis: If you remember back, HRS can be differentiated from other causes of AKI because it is not volume responsive. For an adequate volume challenge, we give albumin 1 g/kg x 48 hr and stop all diuretics. If the Cr fails to improve after the albumin challenge, this is suggestive of HRS. 

Definition: There are two types HRS. 

  • Type 1 is severe, rapidly progressive and has high mortality (mean survival of ~ 2 weeks). It is defined by an ↑ in Cr > 2.5 within 2 weeks.
  • Type 2 is slowly progressive over weeks to months and often results in moderate renal insufficiency. Mean survival time is 4-6 months. 
Pathophysiology in Decompensated Cirrhosis

Add “De” to the previously written “compensated” and add an additional downward arrow in front of the liver function to indicate worsening function. The numbering below corresponds to the diagram. Draw each section of the diagram as you work through the steps.

  1. Worsening liver dysfunction results in loss of compensatory increase in cardiac output (for a variety of reasons that includes development of cirrhotic cardiomyopathy), which results in systemic hypotension and ↓ EAV
  2. Systemic hypotension results in ↓ renal perfusion and leads to pre-renal AKI
  3. ↓ EAV results in activation of RAAS (renin-angiotensin-aldosterone system), ADH secretion and ↑ sympathetic tone
  4. This results in water and salt retention and renal arterial vasoconstriction
  5. Which results in progressive hyponatremia and pre-renal AKI
Pathophysiology of Compensated Cirrhosis

Write up “compensated cirrhosis” on the board. Draw each section of the board as you talk through it. The numbering below corresponds with diagram.

  1. Worsening liver function results in ↓ metabolism of vasodilatory substances (e.g. nitrous oxide, carbon monoxide, cannabanoids)5
  2. These substances result in ↓ vascular tone and systemic vasodilation.
  3. The splanchnic (aka, gut) arteries vasodilate which results in
  4. ↓ in effective arterial volume (EAV)
  5. In compensated cirrhosis, the heart increases cardiac output (CO) to compensate so there is minimal change in EAV and plasma volume
Differential of AKI

Start by writing on a blank area of the board. AKI is common in patients with cirrhosis and occurs in ~ 20% of hospitalized patients. It sigificantly increases mortality so prompt evaluation is warranted. 

Fill in the prevalences of pre-renal, renal and post-renal AKI as you mention them. Evaluation of AKI in ESLD should initially include a urinalysis to look for casts and a FeNa or FeUrea to differentiate between pre-renal, renal and post renal causes. The most common causes of AKI in ESLD are pre-renal (>60%). Obstructive AKI only makes up <1% of all causes of AKI so renal US may not be necessary in all patients. 

Additionally, evaluation of AKI in cirrhosis should involve evaluation for infection (even in the absence of fever or leukocytosis), GI bleeding, and liver function. 

Next, have your learners list causes of pre-renal and renal AKI, filling in the table as you go. Highlight that hypovolemia and sepsis result are volume responsive but HRS is not. Not listed on this diagram is cardiorenal cause of AKI, which would worsen with volume repletion.

Higher level learning point: Urine studies are not reliable at distinguishing ATN from HRS in patients with ESLD. Granular casts can be seen in severe hyperbilirubinemia and are not specific to ATN. FeNa may still be low in the setting of ATN in cirrhotics (see pathophysiology below)5. 

CT Interpretation

  • Persistent moderate sized PTX
  • Diffuse isolated R sided ground glass opacities and interlobular septal thickening
  • Multiple upper lobe cystic cavities with air-fluid levels
  • Bilateral apical bullae, bilateral upper paraseptal and centrilobular emphysema

A cyst has thin walls (< 2 mm) and may rarely contain fluid or solid material. A bulla is also thin walled (usually < 1mm, sometimes imperceptible) and is often accompanied by emphysema. Bulla also tend to be subpleural rather than within the lung parenchyma

CXR Interpretation

Causes of Allograft Dysfunction

Additional History

PMH:
#APCKD s/p DDRT (CMV D-/R-, EBV D+/R-) and nephrectomy about 6 months ago

#Post transplant DM 2/2 tacrolimus and pancreatic failure
#Acute renal failure 2/2 BK nephropathy with baseline Cr of 1.5
#Necrotizing pancreatitis s/p necrosectomy and now with intraabdominal drain
#Gout

MEDICATIONS:
– Tacrolimus twice daily – recent increase in dose ~ 1 month prior due to low drug levels

– Prednisone 10 mg daily
– Insulin
– Darbepoetin
– Lansoprazole
– Completed 2 week course of doxycycline and fluconazole one day prior to presentation

ROS:
– No for history volume depletion

– No infectious symptoms (fevers, chills, localizing signs/ symptoms of infection)
– No medication nonadherence or new medications except for doxcycyline and tacrolimus

Hyperkalemia Treatments

  • In patients with renal dysfunction, IV insulin 5 U is recommended over full 10 U with D50W.
  • Kayexelate, or sodium polystyrene sulfonate
    • Should not be given to patients with history of recent bowel surgery, ileus, or constipation as it can cause bowel necrosis
    • Should not be used for mild hyperkalemia given risk of bowel necrosis
    • Thought to lower serum K comparably to laxative therapy
Hyperkalemia ECG

Show ECG interpretation
Peaked T waves throughout the precordial leads.

The progression of ECG changes: Peaked T waves, shortened QT interval → PR prolongation, PR flattening → QRS widening → sine wave

Large Vessel Complications of GCA

Above table adapted from information from Hoffman, GS et al, 2016 and Buttgereit F, et al, 2016.

Pulsus Paradoxus

Auscultate for the systolic blood pressure.  As you decrease the cuff pressure, take note of the pressure when you can first hear a Korotkoff sound (audible heartbeat). These sounds are initially only present on expiration and disappear with inspiration. Continue to lower the cuff pressure until you can here Korotkoff sounds throughout the respiratory cycle. Pulsus paradoxus is defined as difference between these pressures of >10 mmHg. If the difference is >12 mmHg in a patient with a pericardial effusion, it is 98% sensitive and 83% specific for tamponade.

This patient had a pressure difference of 6 (no pulsus paradoxus). TTE confirmed no evidence of tamponade.

Of note, pulsus paradoxus is not a paradox at all. It is an exaggeration of the normal effects of the respiratory cycle on blood pressure. During inspiration, negative intrathoracic pressure increases venous return to the right heart. Increased right ventricular pressures result in mild bowing of the septum into the left ventricle and results in decrease in cardiac output and thus blood pressure. With cardiac tamponade, there is ventricular interdependence so septal bowing into the left ventricle during inspiration is more pronounced.

CT Chest Interpretation

Pseudohyponatremia and Hyperosmotic Hyponatremia

Artifact or pseudohpyonatremia (i.e. hypertriglyceridemia) – Most of our plasma is water plasma, but there is also a small percentage (around 7%) that is made up of lipids and proteins.  What we really care about is the water plasma.  However, our standard plasma [Na] lab measures the whole plasma. When there are a lot of lipids (i.e. hypertriglyceridemia) or lots of protein (i.e. multiple meyloma) this will dilute our measurement and give us a falsely low [Na], even though the [Na] in the water plasma is still normal.  To verify that this is the case send a ‘whole blood’ [Na], which will just measure the water plasma.

Active Osm (i.e. Glucose) – compounds that do not freely cross the cell wall and osmotically pull water out of the cell, into the extracellular plasma in order to equilibrate the Osm gradient and consequently diluting the concentration of Na.

Inactive Osm (i.e. BUN and EtOH) – Freely cross the cell membrane and thus do not pull water into the extracellular plasma.  However, these Osm are occasionally the consequence of a primary process (i.e. renal failure or EtOH abuse) that can also explain the patients hyponatremia.

Differential Diagnosis of Neutropenia

Differential diagnosis for neutropenia4

  • Genetic disorders – e.g., benign familial neutropenia, cyclic neutropenia
  • Infections (below list is not comprehensive)
    • Post-infectious
    • Sepsis
    • Viral – HIV, CMV, EBV
    • Bacterial – TB, typhoid, rickettsial
  • Nutritional deficiencies – B12, folate, copper
  • Collagen vascular diseases/ Autoimmune disorders
  • Hematologic disorders
    • Myelodysplasia
    • Aplastic anemia
    • Acute leukemia
  • Drugs/toxins
    • Antibiotics – penicillins, cephalosporins, vancomycin, Bactrim, macrolides
    • Antifungals – amphotericin, flucytosine
    • NSAIDS – ibuprofen, sulfasalazine
    • Antithyroid drugs – methimazole, propylthyiouricil
    • Psychotropic medications – TCAs
    • Anti-epileptics – carbamazepine, phenytoin, valproate
    • Cardiac drugs – antiarrhythmics, ACE inhibitors, digoxin
    • Diuretics – thiazides, furosemide, spironolactone
    • Other – levamisole
Transfusion Reactions by Symptomology

CXR Interpretation

CT Results

CT  KUB: non-obstructing renal calculi w/o hydronephrosis, large hiatal hernia, multiple pulmonary  nodules in the bilateral bases

CT Chest: 

http://teachim.org/wp-content/uploads/2015/06/Brandon-Pnt-CT-Shorter-2.mp4

 

Image from: Husain, Z, et al. “DRESS syndrome: Part I. Clinical perspectives.” 2013. Journal of American Academy of Dermatology. 68:693.e1

Physical Exam

Image from: Husain, Z, et al. “DRESS syndrome: Part I. Clinical perspectives.” 2013. Journal of American Academy of Dermatology. 68:693.e1

PMH and Medications

PMH:
#CAD with history of NSTEMI, LVEF 50%
#Epilepsy: well controlled on lamotrigine up until ~ 6 weeks ago when he was admitted for breakthrough seizures

MEDICATIONS:
Aspirin daily

Atorvastatin daily
Losartan daily
Metoprolol daily
Lamotrigine twice daily (stable dose x years)
Phenytoin – stopped 5 days ago
Acetaminophen as needed (has taken “several doses” over the past week”
Vicks PM x 2-3 doses over the past week

Shunt Fraction and Response to Oxygen

Shunt fractions > 50% have no response to 100% FiO24. Acute causes of large shunt in the hospital include flash pulmonary edema, large aspiration event, pneumothorax and mucus plugging resulting in lobar collapse.

Causes of Secondary ITP

Additional Labs for Secondary ITP

Other laboratory studies to consider for evaluation and work-up of secondary causes of ITP3:

  • Pregnancy test – negative
  • ANA
  • Antiphospholipid antibodies – ultimately negative
  • HIV – negative
  • HCV – negative
  • H. pylori testing
Initial Physical Exam and Labs

PHYSICAL EXAM:
VS: T 39C, HR 109, BPs 120s- 140s/80s, RR 16, SaO2 99% on RA

GEN: Well appearing, no acute distress, warm to touch
HEENT: Moist mucus membranes
NECK: Supple, full ROM
CV: Tachycardic, RR, no m/r/g.
PULM: Clear to auscultation bilaterally.
ABD: Scars from prior transplant. Nontender over graft, no CVA tenderness.
MSK: Normal bulk and tone
SKIN: Warm, diaphoretic.  No rashes.

LABS (at the OSH ED):
BMP – Na 121, K 4.5, Cl 92, HCO3 21, BUN 18, Cr 1.6 (baseline Cr of 1.3)

Glucose 156
CBC – WBC 11.3, Hgb 16/hct 47, Plts 192
Lactate 1.6

PMH and Medications

PMH:
#DDRT ~ 6 years ago for ADPKD

– CMV D+/R-
#CKD, baseline Cr of ~ 1.3
#Detrusor muscle failure resulting in bladder overdistention and urinary obstruction resulting in chronic hydroureteronephrosis (of native kidneys)
#Prior episodes of CoNS UTIs resistant to oxacillin
#HTN
#DM type II 2/2 to steroids

MEDICATIONS:
Allopurinol daily

Amlodipine daily
Valsartan twice daily
Asa daily
Calcitriol daily
Glipizide daily
Levothyroxine daily
Mycophenylate twice daily
Prednisone daily
Tacrolimus twice daily

PMH and Medications

PMH:
#CVID
#Hypercoagulability complicated by portal venous thrombosis

#Portal hypertension resulting from portal venous clot
– History of esophageal varices
– History of splenomegaly
#S/p splenectomy (for splenomegaly)

MEDICATIONS:
Aspirin daily
Penicillin twice daily (prophylaxis for splenectomy)
Bactrim three times/week (prophylaxis while on steroids)
Prednisone 10 mg daily 
Methotrexate weekly
Meloxicam daily
IVIg weekly
Omeprazole daily
Spironolactone daily

Laboratory Work-up

BMP: Na 132, K 3.7, Cl 101, HCO3 20, BUN 23, Cr 1.3, Ca 9.2
CBC: WBC 24 (95% PMNs, low lymphocytes, no eosinophils), hct 39, plts 221
Lactate 1.4
Troponin negative
BNP 123
ABG: 7.46/27/64/19 on 2 L NC

CXR (initial): clear with residual left basilar scarring
EKG: sinus tachycardia without signs of right heart strain or ischemic ST changes

PMH and Medications

PMH:
#BOLT  ~10 years ago for COPD
– CMV D+/R-
– history of pulmonary mold infection treated with a course of voriconazole
– course complicated by cellular rejection 3 weeks ago treated with r-ATG (rabbit-derived antithymocyte globulin) and high dose steroids
#HTN
#GERD
#Chronic HCV

MEDICATIONS:
Amlodipine daily
Asa daily
Atorvastatin  daily
Ca-Vitamin D
Metoprolol BID
Omeprazole daily
Prednisone  daily
Bactrim DS 1/2 tab daily
Tacrolimus twice daily (no change in dose recently)
Valganciclovir ppx started ~ 3 weeks ago with r-ATG reinduction
Stopped mycophenylate mofetil ~ 3 week ago with r-ATG reinduction

Laboratory results

– Coags – PT 16.1, INR 1.3, PTT 43
– LDH 2054
– Haptoglobin <30
– Peripheral smear is included below
– Reticulocyte count 

– LFTs – AST 108, ALT 56, ALP 56, Tbili 1.0 (direct 0.3), Total protein 6, albumin 2.7
– Stool studies – viral, bacterial, O/P, and C. diff were negative

– Carbamazepine and leveteracitam levels subtherapeutic

TTP - labs 2

Secondary work-up:
– Stool studies – viral, bacterial, O/P, and C. diff were negative
– Flu and RSV negative
– Pregnancy negative

TTP work-up:
– ADAMSTS 13 activity was 0%
– Antibody 14 U/mL (borderline)
– Inhibitor – 0% (mixing study)

Schistocytes

The above peripheral blood smear shows evidence of schistoctyes.

Labs

BMP – Na 138, K 3.2, Cl 109, HCO3 21, Cr 1.64, BUN 26
(baseline Cr is normal)

CBC – WBC 7.5, hct 18 (Hgb 5.8), plt 9
(baseline hct and platelets are normal)

Complications of Immunosuppresion

This section serves as a broad overview of different types of complications that occur after transplantation and their timing in relation to initial transplant. Draw in each row/category as you teach them. The added text in this section is highlighted by a green box and not in green text in order to showcase different marker colors.  

Immunosuppression

Allogenicity can be thought of as a patient’s risk of rejection. It is the highest in the first month after transplant and decreases over time. This is important in understanding the type of immunosuppression used in induction (heavily immunosuppressing) and in maintenance. 

For induction, high dose steroids are used in combination with anti-lymphocyte or anti-IL2 antibodies. These are very immunosuppressing and their effects can last for several months after their initial use (duration of effect depends in part on “depleting” vs. “nondepleting” antibodies)

Maintenance immunosuppression can be divided into 3 general categories:
– steroids (almost exclusively prednisone)
– anti-metabolites (azathioprine, mycophenylate)
– calcineurin inhibitors (tacrolimus, cyclosporine)

mTOR inhibitors such as sirolimus and everolimus are also used in certain transplant patients. 

Balancing Immunosuppresion

The first section of this talk is on balancing immunosuppresion. The new figures you will draw are added in green. Please look to the next figure for color coding this figure. 

Too much immunosuppresion increases risk of infection and cancer, while too little results in rejection of the transplanted organ. Among the different transplant organs, lungs have the highest risk of rejection and livers hace the lowest risk. This risk is reflected in the number of maintenance immunosuppressant medications patients are on. 

Maintenance immunosuppression can be divided into 3 general categories:
– steroids (almost exclusively prednisone)
– anti-metabolites (azathioprine, mycophenylate)
– calcineurin inhibitors (tacrolimus, cyclosporine)

Board Set Up

Set up your board prior to the start of the lecture. Use different colored markers/chalk if possible. In general, medications and infectious/malignant complications appears as blue; rejection complications appear as red. 

CT findings

  • 20 x 33 mm spiculated anterior segment left upper lobe mass contacting the pleura with a small pleural effusion, concerning for lung cancer
  • Additional spiculated pulmonary nodules are present in the left upper lobe (9 x 12 mm) and the right upper lobe (8 mm). These are suspicious for metastatic foci
Rheumatologic Labs

  • ESR 38 (H), CRP 124.5 (H)
  • ANA panel negative
  • ANCA positive 1:64
    • Anti-PR3 >80 (H)
    • Anti-MPO negative
  • Anti-GBM negative
  • Total complement 42
    • C3 – 84 (L)
    • C4 – 5 (L)
Multinucleated Giant Cell

Differential Diagnosis and Evaluation

The differential for hypoxia and dyspnea in the hospital can be differentiated into respiratory, cardiac, and other causes. Anything in the respiratory system (comprised of airways, alveoli, vessels) that is narrowed, blocked, or collapsed results in dyspnea and usually hypoxia. Walk through each level of your diagram (from upper airways down). 

Cardiac and other causes may cause dyspnea with or without concurrent hypoxia. Walk through notable cardiac causes and then discuss the 3 “A’s” that comprise the “other” causes. Acidosis, for example, results in tachypnea without hypoxia. 

In discussing work-up and evaluation, physical exam and response to oxygen is the first step. A CXR easily identifies any alveolar/parenchymal or pleural process. Alveolar processes in addition to bronchoconstruction and PE will result in a low PaO2. 

The 5 Causes of Hypoxemia

Introduce part (1) as identifying and differentiating the 5 causes of hypoxemia, which can be separated by normal A-a gradient and elevated A-a gradient cause. While explaining the A-a gradient, draw the equation on the board. 

Engage your learners in guessing the causes of normal A-a gradient hypoxemia. When, they identify decreased FiO2 as a cause, mark it with an “X” to denote that this is not relevant in the inpatient setting. Give examples of (or ask your learners to identify)  each cause of hypoxemia as your learners identify them.

Next, engage your learners in identifying the remaining 3 causes of elevated A-a gradient hypoxemia. Differentiate shunt by its nonresponse to 100% FiO2. In fact, all other causes of hypoxemia except for a large shunt (> 50%) will correct with 100% FiO2.  Mark out diffusion impairment as a notable cause of inaptient hypoxemia. 

While giving examples of V/Q mismatch and shunt, you can illustrate them on the alveoli/vessel diagram. A PE and alveolar filling process are shown. 

Teaching Instructions: Board Set Up

Prior to the start of the lecture, set up your board as detailed in the figure. Split the board in half. On one side, draw the flow sheet in (1) but leave the 5 causes of hypoxemia blank. On the other side, draw the diagram in (2). 

You can teach either part 1 or 2 first. Teaching part 1 first builds a basic understanding of different pulmonary causes of hypoxemia that can help with differential building and understanding the utility of different laboratory tests in the evaluation of hypoxia in part 2. Teaching part 2 first helps lay a general ground work for how to think about dyspnea and hypoxia in the hospital before focusing in on pulmonary causes of hypoxia. 

Labs and Imaging

CXR– differentiates and identifies any alveolar filling process, atelectasis or pleural process
Venous blood gas– evaluates for a component of hypoventilation that could be contributing to hypoxia or metabolic acidosis driving respiratory rate
Arterial blood gas– in addition to information provided by a VBG, an ABG measures PaO2 (arterial partial pressure of oxygen) which confirms hypoxemia, can be used to calculate an A-a gradient
EKG– assess for arrhythmias, ischemic changes, low voltages or electrical alternans
Echocardiogram– while a formal TTE is not often possible in the immediate evaluation of new hypoxia, a bedside ultrasound can assess for presence of a pericardial effusion or signs of right ventricular overload (more skilled operators)
Troponin– elevated in ACS or instances of demand ischemia
B-type naturietic peptide– elevated in heart failure exacerbations
BMP– identifies presence of acidosis
CBC– identifies anemia

D-dimer testing is not included in the above list because it has limited utility in already hospitalized patients for evaluation of pulmonary embolism. If there is high suspicion of PE, a CTPE or V/Q scan should be considered for evaluation.

Physical Exam

Vital signs: respiratory rate, pulse oximetry in particular
ENT:  signs of lip, tongue, or posterior oropharyngeal swelling, stridorous breath sounds
Pulmonary: ability to speak in full sentences, shallow breathing, accessory muscle use, bilateral chest rise, presence or absence of breath sounds, abnormal breath sounds (crackles, wheezing, rhonchi)
Cardiac: murmurs, extra heart sounds such as S3 or S4, JVP
Abdomen: abdominal distention
Extremities: edema, signs of DVT, peripheral cyanosis

Evidence for HFNC

The FLORALI study (NEJM, 2015) was a multicenter study that randomized 313 patients with acute hypoxemic respiratory to receive HFNC, standard oxygen therapy (continuous NRB face mask) or NIPPV and evaluated intubation rates and mortality. The study found there was no statistically significant difference in intubation rates between the 3 groups at 28 days. However, there was a statistically significant difference in all cause mortality at 90 days and in ventilator free days at 28 days. Subgroup analysis did show that in patients with more severe hypoxemia (PaO2/FiO2 ratio < 200), there was a statistically significant difference in intubation rates at 28 days.

HFNC also potentially lower risk for reintubation. Hernandez, et al. in 2016 in JAMA randomized 527 patients to HFNC or conventional oxygen therapy (nasal cannula or NRB) after extubation. At 72 hours, reintubation rates were 4.9% in the HFNC group compared to 12.2% in the conventional group (p = 0.004). Subsequent studies9 looking at patients at higher risk for extubation failure have not demonstrated statistically significant difference.

Oxymizer

The graph on the left is a model of effective FiO2 for oxymizer compared to standard nasal cannula. Oxymizer consistently delivers ~ 8% higher FiO2 when compared to standard nasal cannula. The graph on the right is from the manufacter’s detail which shows that the fluidic oxymizer achieves similar FiO2‘s in the trachea as compared to high flow nasal cannula.

Streptoccal TSS skin rash

 

Image from Stevens, DL in Uptodate.

How does IVIg work?

IVIg can be considered as adjunctive therapy, but is not supported by robust clinical evidence. Theoretically, it provides anti-inflammatory and immunomodulatory effects by boosting antibody levels via passive immunity. It has been shown to improve mortality in retrospective, observational studies and only one small, randomized trial2,4.

How does adjunctive clindamycin therapy help?

Streptococcal species, in particular, Group A Streptococcus is very sensitive to beta-lactam inhibitors but monotherapy with penicillin has been associated with high mortality. The Eagle Effect is thought to be responsible in part for this high mortality rate1,2. Penicillins require actively replicating bacteria in order to inhibit bacterial wall synthesis. Large inoculums of bacteria reach a stationary growth phase and decrease expression of penicillin binding proteins, reducing the efficacy of penicillins.

Clindamycin adjunctive therapy improves outcomes when used in conjunction with beta-lactam therapy. Clindamycin reduces protein synthesis and decreases production of bacterial toxins. It may also decrease production of cytokines by our immune cells and modulate immune response.

ABG interpretation

He has an acute respiratory acidosis and evidence of hypercarbic respiratory (or ventilatory) failure. He is also hypoxemic with an elevated A-a gradient of >200.

Chest CT interpretation

Patchy basilar consolidation. Scattered bilateral small pulmonary nodules identified and may reflect an infectious process similar to basilar consolidation.

BAL cultures

  • Bacterial culture – stain negative, final culture negative
  • AFB stain and culture negative
  • Fungal stain and culture negative
  • Mycoplasma and Aspergillus PCR negative
  • PJP stain and PCR negative
  • Nocardia and Legionella cultures NGTD
Other

  • Pulmonary edema and pleural effusions are common in the early post operative setting because of the disruption of lymphatic drainage system during transplantation
  • Bronchial stenosis is the most common airway complication
    – Most commonly manifests in the first month post-transplant but sometimes manifests multiple years after transplant
  • Pulmonary emboli – higher incidence in lung transplant patients14
    –  VTE (including DVTs) occured in up to 49% of post lung transplant patients
    – ~ 60% of VTEs occur within the first year after transplant (with 40% of these cases occuring in the first 3 months) 
  • PTLD
    – Most common in the first year post-transplantation
    – Patients who are EBV seronegative have a higher risk of developing PTLD
    – Occurs in 2-8% of lung transplant patients
    – Cases that occur in the first year involve the grafted organ, but later cases can involve other organs (frequently the GI tract)6
  • Recurrent primary lung disease
    – Sarcoid has recurrence of 35% after lung transplant and has been reported between 2 weeks – 2 years post-transplant6
  • Pulmonary drug toxicity
    – Can occur with mTOR inhibitors (everolimus, sirolimus)
    – Most common within the first 6 months of starting therapy
Rejection

Infections

  • Bacterial
    • Make up the vast majority of post-transplant infections (40-60% of  all infections)
    • Nosocomial organisms such as MRSA and Pseudomonas are most common in the first month after transplantation
    •  Recurrent infections with gram negative bacteria (most commonly Pseudomonas) can occur years after transplant, particularly in patients with bronchiectasis or bronchiolitis obliterans
  • Fungal
    • Aspergillus
      – Most common fungal infection
      – High rates of post-transplant colonization
      – Invasive disease occurs in ~5% (with incidence ranging from 3-22%) of patients with most cases occuring in the first year3,4
    • Endemic mycoses – most commonly occur > 6 months out
    • Pneumocystic jirovecii pneumonia
      – Previously high incidence of infections but now is less commonly seen because of the use of prophylaxis
      – Most common 3-6 months post transplant4
      – May be sublinical in up to 50% of cases4
  • Viral
    • CMV
      – Mostly occurs 1-3 months after transplant, but increasing cases of delayed CMV infection with valganciclovir prophylaxis4,6
      – CMV negative recipients who receive CMV positive doonor lungs are at highest risk
      – Can involve any organ but common in transplanted organ
Labs

BMP: Na 132, K 3.7, Cl 101, HCO3 20, BUN 23, Cr 1.3
Mg 1.4, Ca 9.2
Lactate 1.4
CBC: WBC 24 (95% PMNs, low lymphocytes, no eosinophils), hct 39, plts 221
LFTs: all normal

Additional Medical History

PMH:
#BOLT  ~10 years ago for COPD
– CMV D+/R-
– cellular rejection 3 weeks ago treated with r-ATG (rabbit antithymocyte globulin) and high dose steroids
#HTN
#CAD

MEDICATIONS:
Amlodipine
Asa
Atorvastatin
Metoprolol
Prednisone 5 mg daily
Tacrolimus twice daily (no change in dose recently)
Bactrim DS daily
Valganciclovir prophylaxis started ~ 3 week ago after receiving r-ATG
Mycophenylate mofetil stopped ~ 3 weeks ago after receiving r-ATG

Labs

BMP – Na 133, K 4.3, Cl 96, HCO3 27, BUN 12, Cr 1.01
CBC – WBC 16 (left shifted), hct 37, plts 196
LFTs – AST 19, ALT 33, ALP 167, Tbili 0.9, protein 6.4, albumin 3.3
Lactate 1.1