When to intubate in GCS?

GCS ≤ 8 requires intubation for airway protection. The patient cannot protect their own airway at this level of consciousness. Motor score is the most prognostically important component.

What is the best initial fluid for sepsis resuscitation?

Lactated Ringer's (LR) is the preferred resuscitation fluid. The SMART trial (2018) showed balanced crystalloids reduced death, new renal failure, and persistent renal dysfunction compared to normal saline.

When to start vasopressors in septic shock?

Start norepinephrine (first-line vasopressor) if MAP remains < 65 mmHg after initial 30 mL/kg crystalloid resuscitation, or earlier if patient is profoundly hypotensive. Do not delay pressors to complete full fluid resuscitation.

Why can serum uric acid be normal during acute gout?

During acute inflammation, IL-6 increases renal urate excretion and redistributes urate from plasma to tissues. Up to 40% of acute gout flares have normal serum uric acid. Joint aspiration with polarized microscopy is needed for definitive diagnosis.

How do you distinguish lupus flare from infection in SLE?

Key clues: CRP is low/normal in flare but elevated in infection. Complement (C3/C4) drops in flare but is normal/elevated in infection. Procalcitonin is elevated in bacterial infection but normal in flare. Anti-dsDNA rises in flare, stable in infection.

What is the difference between DKA and HHS?

DKA features acidosis (pH 600), hyperosmolality (> 320), and minimal ketosis -typically in Type 2 DM. DKA requires insulin drip; HHS requires aggressive fluid resuscitation first.

When to give tPA in acute ischemic stroke?

IV alteplase (tPA) can be given within 4.5 hours of last known well time in eligible patients. CT head must rule out hemorrhage first. For large vessel occlusion, mechanical thrombectomy can be performed up to 24 hours with favorable imaging.

What antibiotics for community-acquired pneumonia?

Inpatient non-ICU: ceftriaxone + azithromycin. ICU: ceftriaxone + azithromycin (add vancomycin if MRSA risk). Outpatient healthy: amoxicillin. Outpatient with comorbidities: augmentin + azithromycin or respiratory fluoroquinolone. Duration: 5 days if clinically stable for 48 hours.

How to interpret iron studies?

Iron deficiency: low ferritin (< 30), high TIBC, low iron, low transferrin saturation (< 20%). Anemia of chronic disease: normal/high ferritin (acute phase reactant), low TIBC, low iron. A ferritin of 50-100 in an inflamed patient may still represent iron deficiency.

What is the correction rate for hyponatremia?

Correct sodium no more than 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome (ODS). For symptomatic severe hyponatremia with seizures, give 3% hypertonic saline 100-150 mL bolus over 10-20 minutes. If overcorrected, use D5W + DDAVP rescue protocol.

When to start antibiotics in meningitis?

Within 30-60 minutes. Do NOT delay antibiotics for LP or CT. Draw blood cultures, start empiric antibiotics (vancomycin + ceftriaxone ± ampicillin if > 50 or immunocompromised), then perform LP when possible. Dexamethasone should be given before or with the first antibiotic dose.

DOACs vs warfarin in antiphospholipid syndrome?

DOACs are contraindicated in APS. The TRAPS trial (2018) showed rivaroxaban was inferior to warfarin with more thrombotic events in triple-positive APS patients. Warfarin with INR target 2-3 is the standard for APS, indefinitely.

How to manage scleroderma renal crisis?

ACE inhibitors (captopril) are life-saving -start immediately and titrate aggressively. Do NOT hold for rising creatinine. Steroids > 15 mg prednisone per day precipitate scleroderma renal crisis. ARBs are NOT a substitute -evidence is only for ACEi.

What are the 4 pillars of heart failure treatment?

Guideline-directed medical therapy (GDMT) for HFrEF: (1) ARNI or ACEi/ARB, (2) beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). All four should be initiated and titrated to target doses.

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PBC / PSC

Two distinct cholestatic liver diseases. PBC: anti-mitochondrial antibody positive, middle-aged women, responds to ursodiol. PSC: associated with UC, beading on MRCP, young men, NO proven medical therapy. Both can progress to cirrhosis.

🔍 Overview

PBC vs PSC Comparison

Feature	PBC (Primary Biliary Cholangitis)	PSC (Primary Sclerosing Cholangitis)
Gender	90% female	~70% male
Age	Middle-aged (40-60)	Young adults (30-40)
Key Antibody	Anti-mitochondrial antibody (AMA) -95% sensitive	p-ANCA (nonspecific)
Imaging	Normal bile ducts on MRCP	Beading on MRCP (multifocal strictures + dilations)
Pathology	Destruction of small intrahepatic bile ducts	Inflammation and fibrosis of intra- and extrahepatic bile ducts
Symptoms	Pruritus, fatigue	Pruritus, jaundice, RUQ pain, cholangitis episodes
Associated Conditions	Sjogren, thyroiditis, celiac, RA	Ulcerative colitis (70%), cholangiocarcinoma
Cancer Risk	Hepatocellular carcinoma (if cirrhosis)	Cholangiocarcinoma (lifetime risk 10-15%), gallbladder cancer, colon cancer (if UC)
Treatment	Ursodiol (UDCA) works	NO proven medical therapy

🚨 Management

PBC Management

First-line: Ursodiol (UDCA) 13-15 mg/kg/day (split BID). Improves LFTs, delays histologic progression, improves transplant-free survival. Poupon, NEJM 1991
Incomplete response to UDCA: Obeticholic acid (Ocaliva) -FXR agonist. Add if ALP >1.67x ULN or bilirubin elevated after 12 months of UDCA. Caution: worsens pruritus significantly. Contraindicated in decompensated cirrhosis (FDA black box). POISE, NEJM 2016
Pruritus management: Cholestyramine (first-line for itch), rifampin, naltrexone, sertraline
Liver transplant for decompensated cirrhosis. PBC can recur post-transplant but rarely clinically significant.

PSC Management

NO proven medical therapy -this is the critical teaching point.
Ursodiol is commonly prescribed but does NOT improve transplant-free survival in PSC. High-dose ursodiol (28-30 mg/kg) was actually HARMFUL -increased mortality, need for transplant, and serious adverse events. Lindor, Hepatology 2009
ERCP with balloon dilation for dominant strictures causing cholangitis or progressive jaundice.
Liver transplant -definitive treatment. PSC can recur post-transplant (~20%).
Cancer screening: CA 19-9 + MRCP annually for cholangiocarcinoma. Colonoscopy annually if concomitant UC (elevated colon cancer risk).

Updated Practice: Ursodiol works for PBC but NOT for PSC. Despite widespread use, ursodiol has not been shown to improve transplant-free survival in PSC. High-dose ursodiol (28-30 mg/kg) was actually HARMFUL in PSC (Lindor, Hepatology 2009). Standard-dose ursodiol may improve LFTs but without clinical outcomes benefit.

🧪 Workup

PBC Workup

AMA (anti-mitochondrial antibody) -95% sensitive and highly specific for PBC. AMA-positive + cholestatic LFTs often sufficient for diagnosis without biopsy.
LFTs -cholestatic pattern: elevated ALP, GGT. ALT/AST may be mildly elevated.
IgM -typically elevated in PBC (vs. IgG in AIH)
Liver biopsy -may not be needed if AMA+ with typical cholestatic LFTs. Shows granulomatous destruction of small bile ducts ("florid duct lesion").

PSC Workup

MRCP -diagnostic study of choice. Shows multifocal strictures and dilations of intra- and/or extrahepatic bile ducts ("beading" or "string of pearls").
LFTs -cholestatic pattern (elevated ALP, GGT).
p-ANCA -positive in ~80% but not specific.
Colonoscopy -screen for UC even if asymptomatic (70% of PSC patients have UC).
CA 19-9 -baseline and annually for cholangiocarcinoma screening.
Liver biopsy -"onion skin" periductal fibrosis is classic but often not needed if MRCP is diagnostic.

💊 Medications

Medications

Drug	Indication	Dose	Notes
Ursodiol (UDCA) PBC 1ST LINE	PBC	13-15 mg/kg/day PO	Improves LFTs and transplant-free survival in PBC. Split BID. Take with food. NOT effective for PSC.
Obeticholic Acid (Ocaliva)	PBC (UDCA-incomplete)	5 mg daily, may increase to 10 mg	FXR agonist. Worsens pruritus. Black box: contraindicated in decompensated cirrhosis. POISE, NEJM 2016
Cholestyramine	Pruritus (PBC/PSC)	4 g BID-QID	First-line for cholestatic pruritus. Separate from other medications by 2-4 hours (bile acid sequestrant binds drugs).
Rifampin	Pruritus (refractory)	150-300 mg BID	Second-line for pruritus. Monitor LFTs (hepatotoxic). Effective in PBC/PSC-related itch.
Naltrexone	Pruritus (refractory)	25-50 mg daily	Opioid antagonist for cholestatic pruritus. Can precipitate opioid withdrawal -start low dose.

🏥 Rounds

Pimp Questions

❓ Why does ursodiol work for PBC but not PSC?

In PBC, toxic bile acids cause destruction of small bile ducts. Ursodiol replaces toxic bile acids with a hydrophilic, non-toxic bile acid, reducing cholangiocyte injury. In PSC, the pathology is fibrosis and stricturing of large bile ducts -a different mechanism not addressed by changing bile acid composition. The high-dose UDCA trial in PSC actually showed HARM -possibly because retained ursodiol above strictures caused hepatotoxicity.

❓ What cancer are you most worried about in PSC?

Cholangiocarcinoma -lifetime risk 10-15%. Can be very difficult to detect because it arises in the setting of already-abnormal bile ducts. Screen with CA 19-9 + MRCP annually. Any new dominant stricture should raise suspicion -brush cytology via ERCP with FISH analysis. Also at risk for gallbladder cancer and colon cancer (if UC).

❓ How do you distinguish PBC from PSC on labs and imaging?

Both are cholestatic (elevated ALP, GGT). PBC: AMA positive (95%), normal bile ducts on MRCP, typically middle-aged woman. PSC: AMA negative, beading/strictures on MRCP, typically young man with UC. The bile ducts on MRCP are the key differentiator -if MRCP is normal but cholestasis persists, think PBC (small duct disease not visible on imaging).

Clinical Examples

📋 Case 1, Primary Biliary Cholangitis (PBC)

Patient: 52F with fatigue and pruritus × 1 year. ALP 380, GGT 290, ALT 62, bilirubin 1.8. AMA positive (titer 1:640). MRCP: normal bile ducts. Liver biopsy: florid duct lesion with granulomatous destruction of small bile ducts.

Key findings: Classic PBC: middle-aged woman + cholestatic labs + AMA positive + normal MRCP. Biopsy confirms but is not required if AMA > 1:40 + cholestatic pattern.

Management:

Ursodiol (UDCA) 13-15 mg/kg/day in divided doses (first-line, slows disease progression)
Assess response at 1 year: ALP < 1.67× ULN = adequate response (Paris criteria)
If inadequate response: add obeticholic acid (FXR agonist) POISE, 2016
Cholestyramine 4g BID-QID for pruritus (bile acid sequestrant). If refractory: rifampin, naltrexone
Screen for osteoporosis (cholestasis impairs vitamin D absorption), hypothyroidism (autoimmune overlap)

Teaching point: PBC is diagnosed by AMA + cholestatic labs, biopsy is rarely needed. Ursodiol slows progression to cirrhosis and improves transplant-free survival. Response at 1 year predicts long-term outcome.

📋 Case 2, PSC with Dominant Stricture

Patient: 34M with UC on mesalamine. Progressive jaundice, pruritus, RUQ pain. ALP 520, bilirubin 6.8, CA 19-9 42 (mildly elevated). MRCP: multifocal beading/strictures with dominant stricture at common hepatic duct.

Key findings: PSC with dominant stricture, must rule out cholangiocarcinoma (CCA). Lifetime CCA risk in PSC is 10-15%. Any new dominant stricture or rapidly rising bilirubin/CA 19-9 is concerning.

Management:

ERCP with brush cytology + FISH analysis of dominant stricture (rule out CCA)
If benign: balloon dilation of dominant stricture ± short-term stent placement
No role for ursodiol in PSC (high-dose UDCA showed harm in trials)
Annual CCA screening: CA 19-9 + MRCP
Colonoscopy annually (PSC + UC = very high colon cancer risk, right-sided predominance)

Teaching point: PSC has no effective medical therapy, treatment is managing complications and screening for malignancy. Liver transplant is the only curative option, but PSC recurs in 20-25% of transplanted livers.

📋 Case 3, PBC-AIH Overlap Syndrome

Patient: 45F with fatigue, ALP 320, ALT 280 (mixed pattern). AMA positive (1:320), ANA positive (1:160), IgG 2800 mg/dL (elevated). Biopsy: interface hepatitis with plasma cells AND bile duct destruction.

Key findings: PBC-AIH overlap syndrome (~10% of PBC patients). Features of both: cholestatic pattern (ALP elevated, AMA+) + hepatitic pattern (high ALT, high IgG, interface hepatitis on biopsy).

Management:

Ursodiol 13-15 mg/kg/day (for the PBC component)
Add prednisone 30 mg daily → taper + azathioprine 50 mg → titrate to 1-2 mg/kg (for the AIH component)
Monitor ALT and ALP separately, both should improve with dual therapy
Check TPMT before starting azathioprine (risk of myelosuppression if deficient)
Long-term: aim for biochemical remission (normal ALT + ALP < 1.5× ULN)

Teaching point: Overlap syndrome is suspected when a PBC patient has disproportionately elevated transaminases (ALT > 5× ULN) or elevated IgG. Biopsy is essential, interface hepatitis confirms the AIH component and justifies adding immunosuppression.

Sample Presentation

Mr. Olsen is a 32-year-old man with ulcerative colitis on mesalamine, presenting with progressive jaundice, pruritus, and fatigue over 3 months. Labs: ALP 480, GGT 320, ALT 85, bilirubin 4.2. p-ANCA positive. MRCP shows multifocal intrahepatic and extrahepatic bile duct strictures with beading pattern. Dominant stricture at the common hepatic duct with upstream dilation.

Key Points: Classic PSC -young man with UC, cholestatic LFTs, beading on MRCP. NO medical therapy improves outcomes. Dominant stricture causing jaundice -refer for ERCP with balloon dilation. Start cholangiocarcinoma screening (CA 19-9 + MRCP annually). Ensure annual colonoscopy for UC-associated colon cancer. Discuss liver transplant referral given progressive disease.

PBC Monitoring

LFTs -q3-6 months. Track ALP response to UDCA. Incomplete response: ALP >1.67x ULN after 12 months.
Bilirubin -rising bilirubin is the strongest predictor of poor prognosis in PBC.
Thyroid function -screen for hypothyroidism (frequently associated).
DEXA -osteoporosis risk is elevated in cholestatic liver disease.
Fat-soluble vitamins -A, D, E, K. Malabsorption from cholestasis.

PSC Monitoring

CA 19-9 + MRCP -annually for cholangiocarcinoma screening.
Colonoscopy -annually if concomitant UC (elevated colon cancer risk). Even after liver transplant.
LFTs -q3-6 months. New cholangitis episodes may indicate dominant stricture.
Gallbladder ultrasound -annually. Increased gallbladder cancer risk. Low threshold for cholecystectomy if polyps found.

📋 Summary

Summary

PBC Key

AMA+, middle-aged women, pruritus. Ursodiol 13-15 mg/kg WORKS.

PSC Key

Beading on MRCP, young men, 70% have UC. NO proven medical therapy.

PSC Cancer

Cholangiocarcinoma risk 10-15%. Screen CA 19-9 + MRCP annually.

UDCA in PSC

Does NOT improve survival. High-dose was HARMFUL. Common but unproven use.

PBC Incomplete

Obeticholic acid (Ocaliva) if ALP >1.67x after 12 months UDCA. Worsens pruritus.

Definitive Tx

Liver transplant for both if decompensated. PSC recurs ~20% post-transplant.