The algorithm

Work through the steps in order. Severe symptoms jump the queue; everything else follows the labs.

1. Screen for severe symptomsVomiting, seizures, deep somnolence, coma or cardiorespiratory distress mean hyponatremic encephalopathy. Give a 3% saline bolus now, aiming for a 4 to 6 mEq/L rise within 1 to 2 hours, then finish the workup. No severe symptoms: go to step 2.
2. Confirm it is hypotonicSerum osmolality below 275 mOsm/kg is true hypotonic hyponatremia. Normal osmolality with very high triglycerides or protein is pseudohyponatremia. High osmolality points to glucose or mannitol; add about 2.4 mEq/L to the sodium for every 100 mg/dL of glucose above 100.
3. Decide acute or chronicDocumented for under 48 hours is acute. If you cannot tell, treat it as chronic, which makes overcorrection the main danger.
4. Read urine osmolality100 mOsm/kg or less means ADH is switched off: primary polydipsia, beer potomania or a tea-and-toast diet. Above 100 means ADH is active, so keep going.
5. Examine volume statusEdema, ascites or a raised JVP point to heart failure, cirrhosis, nephrotic syndrome or kidney failure. Dry mucosa and orthostasis point to volume loss. Neither means the patient is euvolemic.
6. Check urine sodiumIn a dry patient, 30 mEq/L or less suggests extrarenal loss (vomiting, diarrhea, third spacing), and above 30 suggests renal loss (diuretics, primary adrenal insufficiency, cerebral salt wasting). In a euvolemic patient, above 30 fits SIADH.
7. Exclude the SIADH mimicsCheck TSH and cortisol and review the drug list before you call it SIADH. Hypothyroidism, adrenal insufficiency and diuretics, especially thiazides, can produce the same labs.
8. Treat by category at a safe rateHypovolemic: isotonic saline. SIADH: fluid restriction first. Hypervolemic: fluid restriction and treat the cause. In chronic hyponatremia, keep the rise to 10 mEq/L or less in the first 24 hours, and 8 or less if the risk of osmotic demyelination is high.

Sources differ on details. The European guideline gives 150 mL of 3% saline over 20 minutes and the US expert panel 100 mL over 10 minutes; both allow up to three boluses. The US panel allows 10 to 12 mEq/L in 24 hours at normal risk, while the more recent European guideline caps the rise at 10 in the first 24 hours and 8 in each 24 hours after that. This post uses the European limits.

Clue in the stem, next best step

Where students lose points

• Sending a seizing or vomiting patient for a head CT or a full workup first. Severe symptoms are an emergency: bolus first, investigate after.
• Correcting chronic hyponatremia too fast. Osmotic demyelination shows up a few days later as quadriparesis, parkinsonism or a locked-in state. Risk is highest with sodium 105 or lower, hypokalemia, alcohol use disorder, malnutrition or advanced liver disease.
• Choosing 0.9% saline for a euvolemic patient with SIADH. Isotonic saline is for volume depletion. In SIADH it often fails to raise the sodium, and the European guideline treats that failure as a supporting clue for the diagnosis.
• Forgetting the glucose. A sodium of 128 with a glucose of 600 mg/dL corrects to about 140, so the sodium is not the problem.
• Labeling SIADH without checking thyroid and adrenal function and the medication list. Secondary adrenal insufficiency and hypothyroidism are classic look-alikes.
• Missing the rebound. Once volume is restored or a thiazide is stopped, a brisk water diuresis can push the sodium up fast, so recheck it often.

Practice question

A 76-year-old woman is brought to the emergency department after a generalized tonic-clonic seizure at home that stopped on its own after 2 minutes. Her daughter says she has had headaches and worsening confusion for 3 days. Sertraline was started 4 weeks ago for depression, and she takes no diuretics. Temperature is 37.0 C, blood pressure 132/78 mm Hg, pulse 88/min and respirations 16/min. She is drowsy but rousable and vomits twice during the exam. Mucous membranes are moist, there is no edema and the JVP is normal. Labs: sodium 114 mEq/L, potassium 4.1 mEq/L, glucose 96 mg/dL, creatinine 0.8 mg/dL, serum osmolality 238 mOsm/kg, urine osmolality 460 mOsm/kg and urine sodium 58 mEq/L.

Which of the following is the most appropriate next step in management?

1. Restrict free water intake to less than 1 L per day
2. Infuse 0.9% saline at 125 mL/h
3. Give a bolus of 3% saline and recheck the sodium shortly afterward
4. Start oral tolvaptan
5. Send TSH and a morning cortisol and wait for the results before treating

60-second recall

• Serum osmolality that confirms hypotonic hyponatremia – below 275 mOsm/kg.
• Urine osmolality that means ADH is suppressed – 100 mOsm/kg or less (primary polydipsia, beer potomania, tea-and-toast diet).
• Urine sodium cutoff in the European algorithm – 30 mEq/L.
• Maximum rise in the first 24 hours of chronic hyponatremia – 10 mEq/L, or 8 if osmotic demyelination risk is high.
• First-line treatment for chronic SIADH, and the second line – fluid restriction; then urea or a low-dose loop diuretic with oral salt.

Keep going: browse every Shelf Prep post, review initial vs best diagnostic tests, talk a case through out loud with MedRise Viva, or find more study resources on MedRise for students.

Sources

• Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia (European Society of Endocrinology, ESICM and ERBP). Eur J Endocrinol, 2014
• Verbalis JG, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med, 2013
• Adrogué HJ, Tucker BM, Madias NE. Diagnosis and management of hyponatremia: a review. JAMA, 2022
• StatPearls: Hyponatremia. NCBI Bookshelf, updated 2023

MedRise Shelf Prep is educational content for exam preparation only. It is not medical advice and does not replace current guidelines, your school's materials or clinical judgment.

Key prenatal screening and diagnostic test timing by gestational week

10 wks

Cell-free DNA (NIPT)
Chorionic Villus Sampling (diagnostic)

11–13 wks

Combined test:
• Nuchal translucency
• PAPP-A
• Free β-hCG

15–20 wks

Quad screen:
• AFP
• hCG
• Estriol
• Inhibin A

15–20 wks

Amniocentesis (diagnostic)
+ AFP/acetylcholinesterase (NTD)

18–22 wks

Anatomy ultrasound

Vogelstein Model / Chromosomal Instability Pathway
(Accounts for ~80% of sporadic CRC)

1. NORMAL MUCOSA
2. APC mutation (tumor suppressor gene)
3. Hyperproliferative epithelium (early adenoma)
4. KRAS mutation (oncogene)
5. Intermediate adenoma
6. p53 mutation + DCC loss (tumor suppressor genes)
7. Carcinoma

Mnemonic: "AK-53" = APC → KRAS → p53

2. Lynch Syndrome (Mismatch Repair Pathway)

Microsatellite Instability (MSI) Pathway
(MSI is found in ~15% of CRC, mostly sporadic via MLH1 promoter hypermethylation; Lynch syndrome, the inherited autosomal dominant form, causes ~3%)

1. Germline mutation in DNA mismatch repair genes:MLH1, MSH2, MSH6, PMS2
2. Microsatellite instability → Accumulation of mutations
3. Adenoma → adenocarcinoma, with faster progression

Associated with: Endometrial, Ovarian, Gastric, Urothelial, Pancreatic cancers

3. H. pylori → Gastric Cancer Pathway

Correa Cascade (Intestinal-Type Gastric Adenocarcinoma)

1. H. pylori infection
2. Chronic gastritis
3. Atrophic gastritis (loss of parietal cells)
4. Intestinal metaplasia
5. Dysplasia
6. Gastric adenocarcinoma

Also associated: Smoking, salt-preserved foods, blood type A

4. Barrett’s Esophagus → Esophageal Adenocarcinoma

GERD-Induced Metaplasia Progression

1. Chronic GERD
2. Barrett’s esophagus (non-ciliated columnar metaplasia)
3. Low-grade dysplasia
4. High-grade dysplasia
5. Esophageal adenocarcinoma (distal)

Surveillance: EGD every 3–5 years for non-dysplastic Barrett’s

5. Pancreatic Cancer Pathway

Multistep Genetic Mutations

KRAS activation (oncogene)

│

▼

CDKN2A (p16) inactivation

│

▼

TP53, SMAD4/DPC4 inactivation (tumor suppressors)

│

▼

Pancreatic ductal adenocarcinoma

Genetic syndromes:

• Peutz-Jeghers (STK11/LKB1)

• Lynch

• BRCA1/2

6. PSC → Cholangiocarcinoma

Chronic Inflammatory → Neoplastic Sequence

1. Primary Sclerosing Cholangitis (PSC)
2. Chronic biliary inflammation & fibrosis
3. Bile duct dysplasia
4. Cholangiocarcinoma (intrahepatic or hilar)

High-yield: Associated with Ulcerative colitis
Screening: MRCP annually + CA 19-9 trend (controversial)

7. Peutz-Jeghers Syndrome → GI & Extra-GI Cancers

Hamartoma–Carcinoma Sequence (rare)

1. STK11 (LKB1) mutation
2. Hamartomatous polyps (non-malignant but numerous)
3. ↑ Risk of epithelial cancers:
4. - Pancreas
5. - GI (stomach, small bowel, colon)
6. - Breast, Ovary, Cervix

Buzzword: Mucocutaneous pigmentation (lips, oral mucosa)

8. Chronic Hepatitis/Cirrhosis → Hepatocellular Carcinoma

Inflammation → Regeneration → Dysplasia → Neoplasia

1. Chronic liver injury (Hep B/C, Alcohol, NASH)
2. Cirrhosis (fibrosis + regenerative nodules)
3. Dysplastic nodules
4. Hepatocellular carcinoma (HCC)

HCC in Hep B may arise without cirrhosis

9. IBD (Ulcerative Colitis) → CRC

Chronic Inflammation → Dysplasia → Carcinoma

1. Ulcerative colitis >8 years
2. Continuous colonic inflammation
3. Multifocal low/high-grade dysplasia
4. Colorectal cancer

Start colonoscopy screening 8 years after diagnosis
Then every 1–2 years

Summary mnemonics

• "AK-53": Adenoma-Carcinoma = APC → KRAS → p53

• “VILLous is VILLainous”: Villous adenomas more likely to become cancer

• “Peutz = Pigmentation + Pancreas”: GI polyps + dark spots + ↑ pancreatic risk

• “PSC + UC = Cholangiocarcinoma”: Chronic inflammation → bile duct cancer

Q1: What are the steps in the adenoma-carcinoma sequence for colorectal cancer?
A1: The progression involves APC mutation → KRAS mutation → p53 mutation leading to transformation of normal mucosa into invasive carcinoma.

Q2: How does chronic H. pylori infection lead to gastric cancer?
A2: Chronic infection causes atrophic gastritis, leading to intestinal metaplasia, dysplasia, and eventually gastric adenocarcinoma.

Q3: What genetic syndromes increase the risk for pancreatic cancer?
A3: Peutz-Jeghers syndrome, Lynch syndrome, BRCA1/2 (especially BRCA2) and familial atypical multiple mole melanoma (CDKN2A) raise pancreatic adenocarcinoma risk. MEN1 causes pancreatic neuroendocrine tumors, not adenocarcinoma.

Q4: How often should patients with PSC be screened for cholangiocarcinoma?
A4: Screening with MRCP and CA 19-9 is recommended annually, especially if concurrent ulcerative colitis is present.

• Types

  • Adenocarcinoma (lower third)

  • Squamous cell carcinoma (upper two-thirds)

• Risk Factors

  • Adenocarcinoma: GERD → Barrett’s esophagus (intestinal metaplasia → dysplasia → adenocarcinoma)

  • Squamous: Smoking, alcohol, achalasia, caustic ingestion

• Paraneoplastic Syndrome

  • Hypercalcemia (PTHrP secretion by squamous cell)

• Diagnosis

  • Initial: Barium swallow (optional if dysphagia + alarm signs absent)

  • Best: EGD with biopsy

  • Staging: Endoscopic ultrasound (EUS), CT chest/abdomen

• Treatment

  • Resectable: Esophagectomy

  • Locally advanced: Neoadjuvant chemoradiation → surgery

  • Metastatic: Palliative chemo + esophageal stent for obstruction

II. Gastric Cancer

• Types

  • Adenocarcinoma

    • Intestinal type (better prognosis, older patients)

    • Diffuse type (signet ring cells, younger patients)

• Risk Factors

  • H. pylori

  • Smoking

  • Nitrosamines

  • Chronic atrophic gastritis, pernicious anemia

  • Blood type A

  • EBV infection (associated with diffuse type)

• Paraneoplastic Associations

  • Acanthosis nigricans

  • Leser-Trélat sign (sudden seborrheic keratosis eruption)

• Diagnosis

  • EGD with multiple biopsies (>6)

  • Staging with EUS, CT, diagnostic laparoscopy (for peritoneal metastases)

• Treatment

  • Surgery (subtotal or total gastrectomy)

  • Neoadjuvant chemotherapy if T2 or higher stage

  • HER2-positive tumors: Trastuzumab + chemotherapy

III. Small Bowel Cancers

• Types

  • Adenocarcinoma (especially duodenum)

  • Carcinoid tumor (ileum > appendix > rectum)

  • Lymphoma (especially ileal)

  • GIST

• Risk Factors

  • Crohn’s disease → adenocarcinoma

  • Celiac disease → enteropathy-associated T-cell lymphoma

  • Peutz-Jeghers syndrome

• Diagnosis

  • Capsule endoscopy

  • Double-balloon enteroscopy

  • Biopsy for confirmation

• Treatment

  • Adenocarcinoma: Surgical resection

  • Carcinoid: Surgical resection if >2 cm or at base of appendix

  • GIST: Resection + Imatinib for metastatic disease (c-KIT mutation)

IV. Colorectal Cancer

• Types

  • Adenocarcinoma (arises from adenomatous polyps)

• Genetic Syndromes

  • FAP (APC mutation, 100% CRC risk)

  • Lynch syndrome (MLH1, MSH2 mutations)

    • Associated cancers: Endometrial, Ovarian, Gastric

  • MUTYH-associated polyposis

  • Juvenile polyposis

  • Peutz-Jeghers (hamartomatous polyps)

• Screening Guidelines

  • Average risk: Start colonoscopy at age 45, every 10 years

  • 1st-degree relative <60y or 2 relatives any age: Start at 40 or 10 years before earliest case, every 5 years

  • Lynch: Start at 20-25 years, every 1-2 years

• Clinical Presentation

  • Right-sided: Iron deficiency anemia, fatigue

  • Left-sided: Obstruction, "apple core" lesion

• Paraneoplastic

  • Streptococcus bovis (gallolyticus) bacteremia → screen for CRC

• Diagnosis

  • Colonoscopy + biopsy

  • CEA (monitoring)

• Treatment

  • Surgery

  • Chemotherapy for Stage III (node-positive) and high-risk Stage II

  • Rectal cancer: Neoadjuvant chemoradiation preferred

V. Anal Cancer

• Type

  • Squamous cell carcinoma

• Risk Factors

  • HPV 16, 18

  • Immunosuppression (HIV)

  • Smoking

• Diagnosis

  • Biopsy

  • Anal Pap smear in HIV-positive patients

• Treatment

  • Nigro protocol: Chemoradiation (5-FU + Mitomycin C + radiation)

  • Surgery reserved for recurrence

VI. Hepatocellular Carcinoma (HCC)

• Risk Factors

  • Hepatitis B (especially perinatally acquired)

  • Hepatitis C

  • Alcohol cirrhosis

  • Hemochromatosis, alpha-1 antitrypsin deficiency, NASH

  • Aflatoxin (Aspergillus)

• Paraneoplastic

  • Hypoglycemia (tumor consuming glucose)

  • Erythrocytosis (EPO production)

• Screening

  • US + AFP every 6 months in cirrhotics and HBV patients

• Diagnosis

  • Imaging (triphasic CT or MRI): Arterial enhancement + venous washout

  • No biopsy needed if classic imaging!

• Treatment

  • Resect small tumors with preserved liver function

  • Liver transplant (Milan criteria)

  • TACE, RFA for inoperable tumors

  • Advanced disease: atezolizumab + bevacizumab first line (it beat sorafenib in the IMbrave150 trial, NEJM 2020); sorafenib or lenvatinib if immunotherapy isn't an option

VII. Cholangiocarcinoma

• Risk Factors

  • Primary sclerosing cholangitis (PSC)

  • Liver flukes (Clonorchis sinensis, Opisthorchis viverrini)

  • Biliary tract stones (choledocholithiasis)

• Diagnosis

  • MRCP preferred

  • ERCP + brushings/biopsy

• Treatment

  • Surgery (if resectable)

  • Palliative chemotherapy if unresectable

VIII. Gallbladder Cancer

• Risk Factors

  • Gallstones

  • Porcelain gallbladder

  • Chronic Salmonella (typhi) infection

• Diagnosis

  • Ultrasound initially

  • CT for staging

• Treatment

  • Cholecystectomy if early

  • Poor prognosis once metastatic

IX. Pancreatic Adenocarcinoma

• Risk Factors

  • Smoking (strongest)

  • Chronic pancreatitis

  • Diabetes mellitus (new-onset after age 50 = red flag)

  • Obesity

  • Family history

• Genetic Syndromes

  • Peutz-Jeghers syndrome

  • Lynch syndrome

  • BRCA1/2

  • Familial atypical multiple mole melanoma (CDKN2A)

  • (MEN1 causes pancreatic neuroendocrine tumors, not adenocarcinoma)

• Clinical Presentation

  • Painless jaundice (head tumors)

  • Courvoisier’s sign (non-tender enlarged gallbladder)

  • Migratory thrombophlebitis (Trousseau syndrome)

  • Depression

  • Weight loss, anorexia

• Diagnosis

  • First test: CT scan with pancreas protocol

  • Best confirmatory: Endoscopic ultrasound (EUS) + biopsy

  • CA 19-9 elevated (used for prognosis, not diagnosis)

• Treatment

  • Whipple procedure (pancreaticoduodenectomy) if localized to head without metastasis

  • Chemotherapy (FOLFIRINOX, Gemcitabine)

  • Palliative biliary stenting for obstruction

Step 2 CK Special High-Yield Reminders

Quick Shelf Tips

• Progressive dysphagia → Think esophageal cancer (start with solids).

• Painless jaundice → Think pancreatic head cancer or cholangiocarcinoma.

• Right-sided CRC → Iron deficiency anemia in an older adult.

• Left-sided CRC → "Apple core" lesion on imaging.

• H. pylori → MALT → Adenocarcinoma sequence if untreated.

• AFP elevated in HCC (not diagnostic alone).

• Always biopsy to confirm cancer (unless classic imaging like HCC multiphasic CT/MRI).

• Differentials:

  • RUQ Pain

    • Cholecystitis → RUQ US

    • Choledocholithiasis → RUQ US ± MRCP

    • Cholangitis → RUQ US + Blood Cultures

    • Hepatitis → LFTs, Viral Hep Panel

  • Epigastric Pain

    • Pancreatitis → Lipase, Abdominal CT

    • Peptic Ulcer Disease → H. pylori Testing, EGD

    • GERD → Trial of PPI, ± EGD if alarm symptoms

  • RLQ Pain

    • Appendicitis → CT Abdomen (adults), US (kids)

    • Crohn’s Disease → Colonoscopy ± Biopsy

    • Ovarian Torsion (females) → Pelvic US with Doppler

  • LLQ Pain

    • Diverticulitis → CT Abdomen/Pelvis with contrast

    • Sigmoid Volvulus → Abdominal X-ray (coffee-bean sign), CT

  • Diffuse Pain

    • Bowel Obstruction → Upright Abdomen X-ray

    • Mesenteric Ischemia → CTA Abdomen

    • Gastroenteritis → Stool Studies (if severe)

2. Presenting Symptom: Diarrhea

• Differentials:

  • Acute Watery Diarrhea

    • Viral Gastroenteritis → Clinical

    • Food Poisoning (E. coli, Salmonella, Shigella) → Stool Cultures

  • Bloody Diarrhea

    • Dysentery (Shigella, EHEC) → Stool Culture, Shiga Toxin Assay

    • IBD (Ulcerative Colitis, Crohn’s) → Colonoscopy + Biopsy

  • Chronic Diarrhea

    • Celiac Disease → tTG-IgA antibodies, Duodenal Biopsy

    • IBS → Diagnosis of exclusion

    • Microscopic Colitis → Colonoscopy + Random Biopsies

3. Presenting Symptom: GI Bleed

• Differentials:

  • Upper GI Bleed (Melena, Hematemesis)

    • Peptic Ulcer Disease → EGD

    • Esophageal Varices → EGD

    • Mallory-Weiss Tear → EGD

  • Lower GI Bleed (Hematochezia)

    • Diverticulosis → Colonoscopy

    • Angiodysplasia → Colonoscopy

    • Colorectal Cancer → Colonoscopy + Biopsy

4. Presenting Symptom: Jaundice

• Differentials:

  • Pre-hepatic

    • Hemolysis (e.g., G6PD Deficiency) → CBC, Reticulocyte count, LDH, Haptoglobin

  • Hepatic

    • Viral Hepatitis → Hepatitis Panel

    • Alcoholic Hepatitis → AST>ALT (2:1), Elevated GGT

    • Drug-induced liver injury → Medication history + LFTs

  • Post-hepatic (Obstructive)

    • Gallstones → RUQ US

    • Malignancy (e.g., pancreatic cancer) → CT Abdomen

5. Presenting Symptom: Nausea/Vomiting

• Differentials:

  • Gastroenteritis → Clinical

  • SBO (Small Bowel Obstruction) → Abdominal X-ray

  • Gastric Outlet Obstruction → Abdominal CT, EGD

  • Increased Intracranial Pressure → Head CT/MRI (if neurologic signs)

QUICK STRATEGY TIPS

• Always start with RUQ Ultrasound for biliary issues.

• CT Abdomen is a key test for acute abdominal pain when diagnosis unclear.

• Endoscopy (EGD or Colonoscopy) is confirmatory for bleeds and chronic diarrhea.

• Labs (LFTs, Lipase, CBC) are first line when systemic signs are present (fever, jaundice).

• Initial test = first step to confirm suspicion or narrow differential (cost-effective, rapid).

• Best test = most accurate or definitive for diagnosis (often confirmatory, more invasive/expensive).

• Know both for shelf exams, Step 2 CK, and real-life triage decisions.

Cardiology

• Chest pain

  • Initial: ECG, troponins

  • Best: Cardiac catheterization (for ST-elevation MI)

• Suspected aortic dissection

  • Initial: Chest X-ray

  • Best: CT angiography (if stable) or TEE (if unstable)

• Heart failure

  • Initial: BNP or NT-proBNP, Chest X-ray

  • Best: Echocardiogram

• Valvular disease

  • Initial: Auscultation → Echocardiogram

  • Best: Transesophageal echocardiogram (TEE)

• Pericardial effusion

  • Initial: Chest X-ray

  • Best: Echocardiogram

• Rheumatic fever

  • Initial: Throat culture, ASO titer

  • Best: Jones criteria + echo for carditis

• Hypertrophic cardiomyopathy

  • Initial: ECG + Echocardiogram

  • Best: Cardiac MRI

Pulmonology

• Pulmonary embolism

  • Initial: D-dimer (low-risk), CT angio (high-risk)

  • Best: Pulmonary angiography (rarely used today)

• Suspected pneumonia

  • Initial: Chest X-ray

  • Best: Sputum culture + sensitivity

• COPD exacerbation

  • Initial: Chest X-ray, ABG

  • Best: Pulmonary function tests (PFTs) for diagnosis

• Tuberculosis

  • Initial: PPD or interferon-gamma release assay

  • Best: Sputum AFB culture (3x)

• Interstitial lung disease

  • Initial: Chest X-ray

  • Best: High-resolution CT

• Sleep apnea

  • Initial: Clinical history + STOP-BANG

  • Best: Polysomnography

• Cystic fibrosis

• Initial: Newborn screen (immunoreactive trypsinogen)

• Best: Sweat chloride test (CFTR genetic testing supports the diagnosis)

Neurology

• First seizure

  • Initial: BMP (check electrolytes), glucose, tox screen

  • Best: MRI brain

• Stroke (acute)

  • Initial: Non-contrast head CT (r/o hemorrhage)

  • Best: Diffusion-weighted MRI

  Hematology

  1. Iron deficiency anemia

  • Initial: CBC + iron panel

  • Best: Bone marrow iron staining (rarely done)

  1. Thalassemia

  • Initial: CBC + smear

  • Best: Hemoglobin electrophoresis

  1. Lymphoma

  • Initial: Lymph node exam + imaging

  • Best: Excisional biopsy

  1. Hemophilia

  • Initial: Coagulation studies (PT/PTT)

  • Best: Factor VIII/IX assay

  1. Polycythemia vera

  • Initial: CBC + JAK2 mutation

  • Best: Bone marrow biopsy

Hematology/Oncology

• Suspected leukemia

  • Initial: CBC with smear

  • Best: Bone marrow biopsy

• Multiple myeloma

  • Initial: Serum protein electrophoresis (SPEP)

  • Best: Bone marrow biopsy

Infectious Disease

• HIV

  • Initial: Antigen/antibody test

  • Confirm: HIV-1/HIV-2 antibody differentiation immunoassay (HIV RNA if results conflict); then viral load and CD4 count for staging

• Syphilis

  • Initial: RPR or VDRL

  • Best: FTA-ABS (confirmatory)

• Hepatitis B

• Initial: HBsAg, anti-HBs

• Best: HBV DNA (viral load)

1. Hepatitis C

• Initial: HCV antibody

• Best: HCV RNA PCR

1. Sepsis

• Initial: Blood cultures + lactate

• Best: Source-specific imaging/cultures

1. Lyme disease

• Initial: ELISA

• Best: Western blot

1. Malaria

• Initial: Thick and thin blood smear

• Best: PCR (less used in acute settings)

Psychiatry

• New-onset psychosis

  • Initial: Urine drug screen

  • Best: Psychiatric evaluation after ruling out organic causes

Emergency Medicine

• Abdominal trauma

  • Initial: FAST ultrasound

  • Best: CT abdomen with contrast

• Suspected ectopic pregnancy

  • Initial: β-hCG + transvaginal ultrasound

  • Best: Diagnostic laparoscopy (if unstable or inconclusive)

GU / Reproductive

BPH

• Initial: DRE + PSA

• Best: Urodynamic studies (not routine)

1. Prostate cancer

• Initial: PSA + DRE

• Best: Transrectal ultrasound-guided biopsy

1. Testicular cancer

• Initial: Ultrasound

• Best: Orchiectomy + tumor markers (AFP, b-hCG, LDH)

1. Ovarian torsion

• Initial: Pelvic ultrasound with Doppler

• Best: Surgical exploration

1. Ovarian cancer

• Initial: Pelvic ultrasound

• Best: Exploratory laparoscopy + CA-125

GI / Hepatology

1. GERD

• Initial: Clinical diagnosis + response to PPIs

• Best: 24-hour pH monitoring

1. Peptic ulcer disease

• Initial: Upper endoscopy

• Best: Biopsy (rule out H. pylori or malignancy)

1. Celiac disease

• Initial: tTG-IgA antibodies

• Best: Duodenal biopsy

1. Pancreatitis

• Initial: Lipase

• Best: CT abdomen (if diagnosis unclear or complications suspected)

1. Gallstones

• Initial: RUQ ultrasound

• Best: ERCP (if obstruction suspected)

Rheumatology

1. SLE

• Initial: ANA

• Best: Anti-dsDNA + Anti-Smith antibodies

1. Rheumatoid arthritis

• Initial: RF + anti-CCP

• Most specific: anti-CCP; hand and foot X-rays to look for erosions

1. Ankylosing spondylitis

• Initial: X-ray sacroiliac joint

• Best: MRI sacroiliac joints

1. Gout

• Initial: Joint aspiration

• Best: Polarized light microscopy (urate crystals)

1. Vasculitis

• Initial: ESR, CRP, ANCA

• Best: Tissue biopsy

Pediatrics / Neonatology

1. Developmental delay

• Initial: Hearing test, vision screen, lead level

• Best: Genetic microarray testing

1. Congenital hypothyroidism

• Initial: TSH/T4 (newborn screen)

• Best: Confirm with repeat TSH and thyroid scan

1. Intussusception

• Initial: Abdominal ultrasound

• Best: Air or contrast enema (diagnostic + therapeutic)

1. Pyloric stenosis

• Initial: Abdominal ultrasound

• Best: Same (no need for confirmatory)

1. Bronchiolitis

• Initial: Clinical diagnosis

• Best: Nasopharyngeal swab for RSV (if needed)

Ophthalmology & ENT

1. Acute angle-closure glaucoma

• Initial: Tonometry

• Best: Gonioscopy

1. Macular degeneration

• Initial: Amsler grid test

• Best: Optical coherence tomography (OCT)

1. Chronic sinusitis

• Initial: Clinical diagnosis (nasal endoscopy to confirm)

• Best: CT scan of sinuses (plain X-rays are not recommended)

1. Otitis media

• Initial: Pneumatic otoscopy

• Best: Tympanocentesis (rarely needed)

1. Hearing loss

• Initial: Audiometry

• Best: Brainstem auditory evoked response (if sensorineural suspected in infants)

1. Medication Classes Overview

2. Mechanism of Action Comparison

3. Clinical Use Cases

4. Key Step 2/CK + NBME Tips

• Anticoagulants = prevent new clots (do not break existing ones).

• Thrombolytics = used acutely to dissolve thrombi (e.g., ischemic stroke, STEMI without PCI).

• Antiplatelets = arterial clots (e.g., coronary, cerebral) — platelets matter more in high-flow systems.

• Anticoagulants = venous clots (DVT/PE) — coagulation cascade driven.

• Never combine anticoagulants + antiplatelets long term unless absolutely indicated (↑↑ bleeding risk).

• Thrombolytics are contraindicated in most cases of recent surgery, active bleeding, or hemorrhagic stroke history.

Mnemonic: "PAT-A"

Drug Quick Sheet

Master table: exceptions and nuance

NBME/Step-Style Exceptions

1. Atrial Fibrillation

• Use anticoagulants to prevent embolic stroke.

• Don’t use aspirin alone unless patient is at low CHA₂DS₂-VASc score (e.g., score = 0).

• Mechanical heart valve → must use warfarin (NOT DOACs like apixaban).

2. Post-MI

• Dual antiplatelet therapy (DAPT) (aspirin + clopidogrel/ticagrelor) after PCI.

• Avoid triple therapy (anticoagulant + 2 antiplatelets) unless compelling indication — increased bleeding risk.

• If patient is on warfarin for Afib + just got a stent, limit DAPT duration and monitor closely.

3. Ischemic Stroke

• Thrombolytics (alteplase or tenecteplase) within 4.5 hours of onset if the patient meets criteria.

• Do NOT give tPA if:

  • BP >185/110

  • INR >1.7

  • Platelets <100k

  • Glucose under 50 mg/dL (correct it, then reassess)

  • Stroke >1/3 of MCA territory on CT

4. DVT/PE

• Start with heparin, then bridge to warfarin or start DOAC directly.

• Use caution with DOACs when CrCl is under 30 mL/min: most are avoided in end-stage kidney disease, where warfarin or apixaban is used.

5. Pregnancy

• Use LMWH (enoxaparin) or UFH (doesn’t cross placenta).

• Avoid warfarin → teratogenic, esp. in 1st trimester.

• Avoid DOACs → insufficient safety data in pregnancy.

6. Massive PE with Hypotension

• Use thrombolytics (alteplase) if:

  • Patient is unstable (shock, hypotension)

• Do not delay lytics for CT angiogram if clinical signs of massive PE and patient crashing.

Summary: first-line choices and what to avoid

Reversal agents

Which of the following is the most appropriate empiric antibiotic regimen?

A) Vancomycin + Gentamicin
B) Vancomycin + Cefepime + Rifampin
C) Ampicillin + Ceftriaxone
D) Vancomycin + Piperacillin-Tazobactam
E) Linezolid + Ceftriaxone + Gentamicin

Left main coronary artery disease

Left main stenosis of 50% or more is a classic CABG indication.

Triple-vessel disease

70% or more stenosis in all three major vessels (RCA, LAD, LCx), especially with reduced EF or diabetes.

2-vessel disease involving proximal LAD + ↓ EF or diabetes

Failed PCI or restenosis after PCI

High SYNTAX score

Used in cardiology to assess lesion complexity (not tested heavily, but FYI)

PCI (Stenting) is preferred when

Single- or dual-vessel disease not involving left main
Low SYNTAX score
STEMI/NSTEMI with culprit lesion
Unable to tolerate surgery (frail, comorbidities)

USMLE tips

• CABG is not used in acute STEMI unless anatomy requires it or PCI fails

• In patients with diabetes + multivessel disease, CABG improves long-term mortality more than PCI

• If you see "proximal LAD" or "left main" = think CABG

Cardio Question

A 62-year-old man with type 2 diabetes, hypertension, and hyperlipidemia presents with exertional chest pain for the past 3 months. He reports the pain occurs after climbing one flight of stairs and resolves with rest. A stress echocardiogram shows reversible ischemia in the anterior and lateral walls. Cardiac catheterization shows:

• 80% stenosis of the proximal LAD

• 75% stenosis of the LCx

• 70% stenosis of the RCA

What is the best next step in management?

A) PCI with drug-eluting stents
B) CABG
C) Medical therapy alone
D) Repeat stress testing in 6 months
E) Implantable cardioverter-defibrillator (ICD)