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.
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%
A RHC provides important hemodynamic measurements of:
These measurements are important for assessment of the severity of PH and underlying etiology, in particular, differentiating Group 1 and Group 2 PH.
Original data from an NIH registry of 194 patients diagnosed with IPAH.1
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.
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-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).
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.
Teaching Instructions: Have your learners synthesize all the information they learned and apply it to the treatment of the different types of shock.
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.
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.
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).
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:
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”
Uncomplicated cystitis/ pyelonephritis: “PESK”
Catheter-associated UTIs: “SEEKS PP” for CAUTIs
Primary adrenal insufficiency: Both mineralocorticoid (aldosterone) and glucocorticoid replacement needed. Additionally, adrenal androgen repletion is also needed.
>2/3 total daily dose given in the early morning to reflect natural pulsatile nature of cortisol secretion
Central adrenal insufficiency: Only glucocorticoid replacement is needed (and typically at lower doses). Hydrocortisone 10 – 15 mg/24 h.
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.
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
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
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
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.
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.
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.
Cholecystitis occurs when there is inflammation and possible infection in the gallbladder caused by obstruction of the cystic duct by a stone or sludge.
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.
Briefly review biliary anatomy to give a framework for understanding biliary disease.
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.
CT additionally showed some small subcentimeter pulmonary nodules that are indeterminate.
Pulmonology was consulted and she underwent a bronchoscopy:
Review of recent CT C/A/P without lymphadenopathy or splenomegaly.
Johns Hopkins GI and Hepatology website: https://gi.jhsps.org/Upload/200802291654_10407_000.jpg
Clinical Gastroenterology and Hepatology Journal: http://www.cghjournal.org/cms/attachment/2006110911/2027664469/gr5.jpg
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.
This rules out benign J point elevation as an explanation for the ST segment elevations seen on the first ECG.
Accelerated idoventricular rhythm w/ L bundle morphology at a rate of 80 with occasional sinus beats.
Findings suspicious for septic emboli or fungal infection.
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 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
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:
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:
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.
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).
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 ___. “
Return to your table in section 2 of your board.
General management principles applicable to all patients with pulmonary hypertension include:
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.
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.
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).
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.
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:
GP only antibiotics that cover MRSA:
PO antibiotics that cover MRSA:
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.
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.
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
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
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.
Fun Mneumonic for Enterococcus spp.
The numbering corresponds to the discussed treatment option.
The pathophysiology of HRS is critical in understanding the treatment options.
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.
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.
Write up “compensated cirrhosis” on the board. Draw each section of the board as you talk through it. The numbering below corresponds with diagram.
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.
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
#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
– Tacrolimus twice daily – recent increase in dose ~ 1 month prior due to low drug levels
– Prednisone 10 mg daily
– Completed 2 week course of doxycycline and fluconazole one day prior to presentation
– 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
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
Above table adapted from information from Hoffman, GS et al, 2016 and Buttgereit F, et al, 2016.
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.
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 for neutropenia4
CT KUB: non-obstructing renal calculi w/o hydronephrosis, large hiatal hernia, multiple pulmonary nodules in the bilateral bases
Image from: Husain, Z, et al. “DRESS syndrome: Part I. Clinical perspectives.” 2013. Journal of American Academy of Dermatology. 68:693.e1
#CAD with history of NSTEMI, LVEF 50%
#Epilepsy: well controlled on lamotrigine up until ~ 6 weeks ago when he was admitted for breakthrough seizures
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 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.
Other laboratory studies to consider for evaluation and work-up of secondary causes of ITP3:
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)
CBC – WBC 11.3, Hgb 16/hct 47, Plts 192
#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
#DM type II 2/2 to steroids
Valsartan twice daily
Mycophenylate twice daily
Tacrolimus twice daily
#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)
Penicillin twice daily (prophylaxis for splenectomy)
Bactrim three times/week (prophylaxis while on steroids)
Prednisone 10 mg daily
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
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
#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
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
– 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
– Stool studies – viral, bacterial, O/P, and C. diff were negative
– Flu and RSV negative
– Pregnancy negative
– ADAMSTS 13 activity was 0%
– Antibody 14 U/mL (borderline)
– Inhibitor – 0% (mixing study)
The above peripheral blood smear shows evidence of schistoctyes.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
Image from Stevens, DL in Uptodate.
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.
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.
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.
Patchy basilar consolidation. Scattered bilateral small pulmonary nodules identified and may reflect an infectious process similar to basilar consolidation.
BMP: Na 132, K 3.7, Cl 101, HCO3 20, BUN 23, Cr 1.3
Mg 1.4, Ca 9.2
CBC: WBC 24 (95% PMNs, low lymphocytes, no eosinophils), hct 39, plts 221
LFTs: all normal
#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
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