Complete USMLE Step 2 CK E-Book

Azhar ul Haque Sario

• Herausgeber: Azhar Sario Hungary
• Kategorie: Fachliteratur
• Serie: USMLE 2026
• Sprache: Englisch

Seitenzahl: 247

Veröffentlichungsjahr: 2026

Beschreibung

Master the USMLE Step 2 CK with the definitive guide for the 2026 exam landscape.

This isn't just a review book; it's a strategic partner for the modern medical student. Inside, you will find a comprehensive breakdown of the entire 2026 Step 2 CK curriculum, meticulously organized to mirror the clinical reasoning you need on test day. We cover everything from the nuanced management of heart failure and the updated guidelines for cancer screening to the ethical minefields of patient autonomy and the complex algorithms of emergency medicine. You’ll dive deep into Internal Medicine, Surgery, Pediatrics, Obstetrics & Gynecology, and Psychiatry, but we don’t just list facts. We explain the "why" behind the "what," connecting physiology to pathology in a way that sticks. You get specific modules on high-yield topics like the "Sepsis Spectrum," "Trauma Protocols," and the "2026 Immunization Schedule." We’ve stripped away the fluff and focused on the decision nodes—the exact moments where you need to choose between a CT scan and an MRI, or between observation and immediate surgery. It is dense with clinical vignettes, "red flag" warnings, and direct comparisons of similar diseases that often trap students on the exam.

What sets this guide apart is its obsession with the current standard of care. Medical knowledge decays, and what was true in 2022 might be wrong in 2026. This book is built on the very latest guidelines—from the new definitions of Pulmonary Hypertension and the rise of SGLT2 inhibitors in heart failure to the shift in colorectal cancer screening age and the modern management of HIV. While other resources might still be teaching outdated protocols, this guide prepares you for the reality of 2026 medicine. It integrates the "soft skills" of communication, ethics, and systems-based practice directly into the clinical content, recognizing that the Step 2 CK is testing your ability to be a doctor, not just a calculator. We prioritize the "next best step" thinking that defines high scores, helping you navigate ambiguity with confidence. It is written in a clear, engaging voice that respects your time and your intelligence, moving you from passive reading to active synthesis. This is the competitive advantage you need to not just pass, but to excel.

Disclaimer: This publication is independently produced by Azhar ul Haque Sario. The author and publisher are not affiliated with, endorsed by, or sponsored by the National Board of Medical Examiners (NBME), the Federation of State Medical Boards (FSMB), or the USMLE program. "USMLE" is a trademark of the NBME and FSMB. All references to the USMLE and other trademarked terms are used herein for descriptive and educational purposes under the doctrine of nominative fair use.

Leseprobe

Complete USMLE Step 2 CK: 2026 Exam Study Guide

Azhar ul Haque Sario

Copyright

Copyright © 2026 by Azhar ul Haque Sario Published by Azhar Sario Hungary

All rights reserved.

No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the publisher, except in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law.

Legal & Disclaimer The information contained in this book is for educational and entertainment purposes only. While every attempt has been made to ensure the accuracy of the information provided, neither the author nor the publisher assumes any responsibility for errors, omissions, or contrary interpretation of the subject matter herein.

[email protected]

ORCID: https://orcid.org/0009-0004-8629-830X

LinkedIn: https://www.linkedin.com/in/azharulhaquesario/

AI Disclaimer: This book is free from AI use. The cover was designed in Canva. No part of this text may be used to train artificial intelligence models without express permission.

Publisher Details Azhar Sario Hungary Author Website: www.linkedin.com/in/azharulhaquesario

Cataloging Data ISBN:

Google Version

978-3-384-80642-0

eBook Version

978-3-384-80643-7

Paperback Version

978-3-384-80644-4

First Edition: 2026 Printed & Distributed by PublishDrive

Disclaimer: This publication is independently produced by Azhar ul Haque Sario. The author and publisher are not affiliated with, endorsed by, or sponsored by the National Board of Medical Examiners (NBME), the Federation of State Medical Boards (FSMB), or the USMLE program. "USMLE" is a trademark of the NBME and FSMB. All references to the USMLE and other trademarked terms are used herein for descriptive and educational purposes under the doctrine of nominative fair use.

Contents

Copyright

Human Development

Immune System

Blood & Lymphoreticular System

Behavioral Health

Nervous System & Special Senses

Musculoskeletal System & Skin

Cardiovascular System

Respiratory System

Gastrointestinal System

Renal, Urinary & Reproductive Systems

Pregnancy, Childbirth & the Puerperium

Endocrine System

Multisystem Processes & Disorders

Biostatistics & Epidemiology

Social Sciences

About Author

Human Development

Part 1: Infancy and Early Childhood (0–12 Years)

1. The Physiology of Growth: More Than Just Numbers

Growth is the most sensitive indicator of a child's overall health. In the first decade of life, somatic growth—the physical increase in body size—is the report card of nutrition and endocrine function.

The "Normal" Trajectory When you look at a growth chart, do not just look at the dot. Look at the curve. A child at the 10th percentile who has always been at the 10th percentile is likely healthy. A child who was at the 50th percentile and drops to the 10th is in trouble. This is "crossing percentiles," and it is a red flag.

Weight: In the first week of life, it is normal for a newborn to lose up to 10% of their birth weight. This is fluid loss. They should regain this by 2 weeks. If they don’t, we worry about feeding failure.

Length (Height): This is the best indicator of long-term health. Weight can fluctuate with a stomach bug, but height requires sustained nutrition and hormones.

Head Circumference: This is a proxy for brain growth. The fontanelles (soft spots) allow the skull to expand as the brain doubles in size in the first year.

Case Study: The Short Child Imagine a 5-year-old boy who is very short for his age (5th percentile). The parents are worried. You have two main differential diagnoses to distinguish:

Familial Short Stature: The parents are short. The child is growing at a normal speed, just on a lower line. His bone age (an X-ray of the hand) matches his actual age. This is genetics.

Constitutional Growth Delay: The parents are normal height, but the dad mentions he was a "late bloomer" who grew tall in college. The child’s bone age is younger than his real age. This child has "plenty of growth left in the tank" and will catch up later.

2. Neurological Maturation: The March of Milestones

The brain develops back-to-front and top-to-bottom. This is why a baby learns to lift their head before they can walk. The 2026 curriculum emphasizes functional outcomes rather than just rote lists.

The Primitive Reflexes Newborns are born with "software" pre-installed to help them survive. These are primitive reflexes. However, these reflexes must disappear (integrate) to make room for voluntary movement.

Moro (Startle): Disappears by 4-6 months.

Rooting/Sucking: Allows feeding.

Palmar Grasp: Putting a finger in the palm makes the hand close.

Pathology Alert: If a 9-month-old still has a strong Moro reflex or a persistent fisted hand, you must suspect cerebral palsy (CP). The persistence of primitive reflexes blocks the development of motor skills. You cannot learn to hold a spoon if your hand clamps shut every time you touch it.

Developmental Warning Signs

Gross Motor: A child should walk by 12–15 months. Not walking by 18 months is a red flag.

Fine Motor: By age 3, a child should be able to draw a circle. By age 4, a cross. By age 5, a triangle. If a 5-year-old cannot copy a circle, their visual-motor integration is delayed.

Language: This is the most common developmental delay. By age 2, a child should put two words together ("Mommy go"). If a child has no words by 16 months or no two-word phrases by 24 months, refer for audiology (hearing test) immediately.

3. Benign vs. Pathologic: Quelling Parental Anxiety

A huge part of Pediatrics is reassuring parents about things that look scary but are harmless.

Teething Syndrome Parents often blame fever, diarrhea, and ear infections on teething. Do not do this. Teething causes fussiness, drooling, and maybe a very low-grade temperature. It does not cause a fever of 39°C (102°F). If a teething baby has a high fever, look for a urinary tract infection or otitis media.

Physiologic Jaundice Newborns have immature livers. It is common to turn yellow (jaundiced) on day 2 or 3 of life. This is "physiologic."

The Danger Zone: Jaundice that appears in the first 24 hours is never normal. It usually means hemolysis (blood cells breaking down), perhaps due to ABO incompatibility.

Murmurs: The Music of the Heart Blood flows fast in children. This turbulence creates noise, or "flow murmurs."

Benign Murmur: It is soft, changes when the child sits up vs. lies down, and occurs in a healthy, active child (e.g., Still’s Murmur).

Pathologic Murmur: It is loud, harsh (like machinery), or associated with failure to gain weight.

4. Preventive Medicine: The ACIP & Safety

In 2026, the USMLE focuses heavily on public health.

Vaccines and Communication The schedule is complex, but the principles are clear. We give dead (inactivated) vaccines to almost everyone. We are careful with live vaccines (MMR, Varicella, Rotavirus).

The Immunocompromised Child: Do not give live vaccines to a child on high-dose chemotherapy or with severe immune deficiency. Their body cannot handle even a weakened virus.

Vaccine Hesitancy: You will face a vignette where a parent refuses vaccines. Do not get angry. Do not kick them out of the practice. The correct answer is always "acknowledge their fear, provide factual information, and aim for a shared decision."

Injury Prevention

Car Seats: Rear-facing as long as possible (at least until age 2, preferably longer). The neck muscles of a toddler are too weak to survive a whiplash injury facing forward.

Drowning: It is the leading cause of death in toddlers. Fences around pools must be four-sided and self-latching.

Firearms: The most effective way to prevent accidental shooting is to remove the gun from the home. If that is not possible, the gun must be locked, unloaded, and ammunition stored separately.

Part 2: Adolescence and the Transition to Autonomy (13–17 Years)

1. The Physiology of Puberty: The HPG Axis Awakens

Adolescence begins when the brain's "sleep mode" ends. The hypothalamus starts releasing GnRH in pulses. This wakes up the pituitary to yell at the gonads (ovaries/testes) to make hormones.

Tanner Staging (Sexual Maturity Rating) You must be able to describe puberty objectively.

Tanner 1: Pre-pubertal (childlike).

Tanner 2: The beginning. Breast buds in females; testicular enlargement in males.

Tanner 5: Adult maturity.

The Sequence Matters

Girls: They enter puberty earlier. The first sign is breast buds (Thelarche). Menstruation (Menarche) happens about 2–2.5 years after breast buds appear. If a girl starts her period before she has breast development, something is wrong.

Boys: The first sign is testicular enlargement (gonadarche). If a boy’s voice deepens or he gets pubic hair before his testicles grow, he might have an adrenal tumor or using exogenous steroids.

Pathology of Timing

Precocious Puberty: Signs of puberty before age 8 in girls or 9 in boys. This requires an MRI of the brain to rule out a tumor activating the system too early.

Delayed Puberty: No signs of puberty by age 13 in girls or 14 in boys. This is often "Constitutional Delay" (the late bloomer mentioned earlier), but can also be Turners Syndrome or chronic illness like Crohn's disease.

2. Menstrual & Reproductive Health

Dysmenorrhea (Painful Periods) This is the most common complaint in adolescent gynecology. It is caused by prostaglandins causing the uterus to cramp.

Treatment: NSAIDs (Ibuprofen) are the first line because they block prostaglandins. If that fails, oral contraceptive pills (OCPs) are the next step.

Gynecomastia in Males It is very common for 14-year-old boys to develop a small, tender lump under the nipple. This is due to a temporary imbalance of estrogen and testosterone during the growth spurt. It is benign. It resolves on its own. Do not biopsy it. Reassurance is the treatment.

3. The HEEADSSS Exam: The Psychosocial Biopsy

Adolescents rarely complain about what is actually killing them. They come in for acne, but they are suffering from depression or substance abuse. We use the HEEADSSS mnemonic to screen their life.

Home: Who lives with you? Do you feel safe?

Education: Grades failing? Bullying?

Eating: Screening for Anorexia/Bulimia.

Activities: Screen time, sports, hobbies.

Drugs: Vaping, alcohol, pills.

Sexuality: Orientation, partners, protection.

Suicide/Depression: The PHQ-A screen.

Safety: Seatbelts, weapons in the home.

The Confidentiality Doctrine This is high-yield for 2026 ethics. Generally, parents have the right to their child's medical info. However, adolescents have the right to confidential care for:

Contraception/STIs.

Substance abuse treatment.

Mental health (in many jurisdictions).

The Trap: If a 15-year-old admits to being suicidal, you must break confidentiality. Life safety supersedes privacy. You tell the patient, "I care about you too much to keep a secret that could get you killed," and then you tell the parents.

4. Sports Medicine: The Pre-Participation Physical

Before a teen plays high school sports, we check for silent killers.

Hypertrophic Obstructive Cardiomyopathy (HOCM) This is a genetic thickening of the heart muscle. It can cause sudden death during exertion.

The Maneuver: We listen to the heart while the patient does a Valsalva (bears down) or stands up. These maneuvers empty the heart of blood. In HOCM, an empty heart brings the thick walls closer together, making the obstruction worse and the murmur louder.

Contrast: Most benign murmurs get softer when the patient stands.

Concussions The management has shifted from "sit in a dark room for a week" to a gradual, symptom-limited return.

Return to Learn: Goes first. If reading gives them a headache, they stop. Once they can tolerate school, they start...

Return to Play: A step-wise protocol. Light cardio → heavy cardio → non-contact drills → full contact.

Subtopic 1.3: Adult Health Maintenance and Disease Prevention (18–64 Years)

The goal here is simple but profound: Preservation. We are trying to keep the engine running smoothly by catching issues while they are still asymptotic. The "Bible" for this section is the U.S. Preventive Services Task Force (USPSTF).

Crucial Exam Note: On the USMLE, "A" and "B" recommendations are not suggestions; they are mandates. If a question asks for the "next best step" and a patient meets the criteria for an "A" recommendation screening, that is almost always the answer.

I. The Big Four: Cancer Screening Protocols

Cancer screening is high-yield territory. The examiners love to test the "edges"—the exact age to start, the exact age to stop, and the exceptions to the rule.

1. Colorectal Cancer (The Moving Target)

Historically, the magic number was 50. That is no longer true. As we see colorectal cancer rates rising in younger cohorts, the guidelines have shifted aggressively.

The Rule: Screening begins at age 45 for average-risk adults. It continues until age 75.

The Tool: You have options, but they aren't equal.

Colonoscopy: The gold standard. If normal, repeat every 10 years. It’s diagnostic and therapeutic (you can snip the polyp right there).

FIT (Fecal Immunochemical Test): Detects hidden blood. It’s non-invasive but must be done every single year. If it’s positive, the patient must get a colonoscopy.

The Nuance: Be careful with "Family History." The protocol changes if a first-degree relative had colon cancer. In that case, you start screening at age 40 OR 10 years before the relative's diagnosis age—whichever comes first.

Example: A 35-year-old patient comes in. His father was diagnosed with colon cancer at 48. You don’t wait until 45. You start screening at 38 (10 years prior to the father's diagnosis).

2. Cervical Cancer (The HPV Revolution)

The Pap smear is evolving. By 2026, the focus is heavily on HPV (Human Papillomavirus) testing because we know that without HPV, cervical cancer is incredibly rare.

Ages 21–29: We use cytology alone (the Pap smear) every 3 years. We generally avoid HPV testing here because young people clear the virus naturally, and testing leads to unnecessary anxiety and procedures.

Ages 30–65: The preferred method is "Co-testing" (Pap + HPV) every 5 years. Alternatively, primary HPV testing alone every 5 years is acceptable.

The Hard Stop: Screening stops at 65 if the patient has had adequate prior negative screening (three negative Paps or two negative co-tests).

The Hysterectomy Trap: If a woman has had a hysterectomy (with cervix removal) for benign reasons (like fibroids), she needs zero further screening. If it was for cancer (CIN2/3 or worse), she needs screening for 20 years post-surgery.

3. Breast Cancer (The Debate is Over)

For years, there was confusion between starting at 40 or 50. The 2026 alignment is clear regarding the shift.

The Standard: The USPSTF now recommends starting biennial (every 2 years) screening mammography at age 40.

The High Risk: For women with a strong family history (e.g., BRCA1/2 carriers), we don’t rely on mammograms alone. We often use MRI, and we start much earlier—often at age 25 or 30.

The Clinical Reality: Dense breast tissue can hide tumors on a mammogram (like looking for a snowball in a blizzard). In these cases, ultrasound is a common adjunct, though guidelines vary on its routine use.

4. Lung Cancer (The Smoker’s Protocol)

Lung cancer kills more people than breast, colon, and prostate cancers combined. Screening works, but only if you target the right group.

The Candidate: Adults aged 50–80.

The Status: They must be a current smoker OR have quit within the past 15 years.

The Test: Low-dose Computed Tomography (LDCT). Chest X-rays are useless for screening; do not choose them on the exam.

II. The Silent Killers: Metabolic & Cardiovascular Health

You can't feel high blood pressure, and you can't feel high cholesterol—until you have a stroke. That is why we screen.

1. Hypertension (The Hydraulic Pressure)

Who: Every adult over 18.

How: In-office measurement is the start, but it’s flawed due to "White Coat Hypertension" (anxiety spiking BP).

The 2026 Standard: Diagnosis usually requires confirmation outside the office. Ambulatory Blood Pressure Monitoring (ABPM)—where the patient wears a cuff for 24 hours—is the gold standard to confirm the diagnosis before committing someone to lifelong medication.

2. Lipid Disorders (The Sludge in the Pipes)

Screening: Generally starts at age 40, but earlier (age 20) if there are risk factors like diabetes or family history.

The Decision: We don't just treat numbers; we treat risk. We use the ASCVD Risk Calculator.

If the 10-year risk of a heart attack/stroke is >10%, we start a Statin.

Example: A 55-year-old smoker with diabetes and high cholesterol is a walking alarm bell. You don't wait for a heart attack; you start Atorvastatin or Rosuvastatin immediately.

3. Obesity and Lifestyle Medicine

In 2026, obesity is viewed as a chronic, relapsing metabolic disease, not a failure of willpower.

First Line: Comprehensive lifestyle intervention (diet, exercise, behavioral therapy).

Pharmacotherapy: This has revolutionized care. GLP-1 agonists (like Semaglutide or Tirzepatide) are now standard of care for patients with BMI >30 (or >27 with comorbidities) who fail lifestyle changes. These drugs mimic satiety hormones, effectively "turning down the volume" on hunger.

Surgical: Bariatric surgery remains an option for BMI >40 (or >35 with comorbidities), especially if metabolic disease is severe.

4. Smoking Cessation

The single most effective intervention in all of medicine is getting a patient to quit smoking.

Pharmacology:

Varenicline (Chantix): A partial agonist. It tickles the nicotine receptor enough to stop withdrawal but blocks the "buzz" from cigarettes. It is generally the most effective monotherapy.

Bupropion: An antidepressant that helps with cravings. Contraindicated in patients with seizures or eating disorders (bulimia/anorexia) because it lowers the seizure threshold.

NRT (Nicotine Replacement): Patches, gums, lozenges. Often best used in combination (Patch + Gum).

III. Immunization: The Biological Armor

Vaccines are constantly updating. Here is the 2026 snapshot for adults.

Pneumococcal (Pneumonia): The new standard simplifies the old confusion.

Who: All adults >65, or younger adults with risk factors (diabetes, smoking, alcoholism).

The Shot: We now prefer PCV20 (a single dose covers 20 strains). If PCV20 isn't available, we use PCV15 followed a year later by PPSV23.

Herpes Zoster (Shingles):

The Vaccine: Shingrix (Recombinant zoster vaccine).

Who: Adults >50.

Why: Shingles is excruciating, but Post-Herpetic Neuralgia (nerve pain lasting months after the rash) is life-altering. The vaccine is >90% effective. It requires two doses, 2-6 months apart.

Note: You give this even if the patient has had shingles before (to prevent recurrence).

Subtopic 1.4: Geriatric Physiology and Care (65+ Years)

As we cross the threshold of age 65, the body's ability to bounce back (physiological reserve) diminishes. This is the concept of Homeostenosis: the narrowing of homeostatic reserves. A mild urinary tract infection that would annoy a 30-year-old can throw a 75-year-old into delirium and septic shock.

I. Physiology: Normal Aging vs. Pathology

The exam requires you to distinguish what is "normal" from what needs treatment.

Normal Aging (Do not treat):

Presbycusis: High-frequency hearing loss.

Presbyopia: Hardening of the lens (need reading glasses).

Renal: Decreased GFR (kidney filtration slows down).

Sleep: Decreased REM sleep, more frequent awakenings.

Cardiovascular: Increased arterial stiffness (isolated systolic hypertension is common).

Pathological (Must treat):

Severe memory loss (Dementia).

Incontinence (It is common, but never "normal"—it should be managed).

Depression (Sadness is not a normal part of aging).

II. Pharmacokinetics and The Beers Criteria

The mantra for prescribing in the elderly is: "Start Low and Go Slow."

Because the kidneys filter less and the liver metabolizes slower, drugs hang around longer in the elderly body. Furthermore, older adults have less total body water and more body fat.

Water-soluble drugs (like Lithium or Ethanol) reach higher concentrations because there is less water to dilute them.

Fat-soluble drugs (like Benzodiazepines) get trapped in the fat stores and have a massive half-life. A Valium taken on Tuesday might still be causing sedation on Friday.

The Beers Criteria: This is a list of drugs to AVOID in the elderly.

Anticholinergics (e.g., Diphenhydramine/Benadryl): Cause confusion, urinary retention, and constipation. Avoid.

Benzodiazepines: Massive risk of falls and confusion. Avoid.

NSAIDs (chronic use): Risk of GI bleeding and kidney injury. Use with caution.

III. The Geriatric Giants

These are the four massive syndromes that define geriatric care.

1. Instability (Falls)

Falls are the leading cause of fatal injury in the elderly.

Assessment: The "Get Up and Go" test. Watch the patient stand from a chair, walk 10 feet, turn, and sit.

Intervention: It’s rarely one thing. It’s multifactorial. You must reduce sedating meds, fix cataracts, remove throw rugs (home safety), and prescribe strength training (Tai Chi is excellent for balance).

2. Immobility (Pressure Ulcers)

When a patient stops moving, gravity attacks the skin.

Pathophysiology: Pressure cuts off blood flow to the skin, causing necrosis.

Staging (Memorize this):

Stage 1: Non-blanchable erythema (skin is red, doesn't turn white when pressed). Skin is intact.

Stage 2: Partial thickness loss (blister or shallow crater).

Stage 3: Full thickness loss (you see fat).

Stage 4: You see muscle, tendon, or bone.

Prevention: Frequent turning (every 2 hours) is the only proven prevention. Donut cushions actually make it worse by focusing pressure; do not use them.

3. Incontinence (Not a function of age)

You must categorize it to treat it.

Urge Incontinence: "I have to go right NOW." Caused by detrusor muscle overactivity. Treatment: Bladder training and Anticholinergics (carefully).

Stress Incontinence: Leaking with laughing, sneezing, coughing. Caused by weak pelvic floor. Treatment: Kegel exercises.

Overflow Incontinence: The bladder is full but won't empty (like a dam overflowing). Common in BPH (prostate issues) or diabetes (nerve damage). Treatment: Catheterization or Alpha-blockers (for BPH).

4. Intellectual Impairment (The 3 D's)

This is the most critical differential diagnosis in geriatrics.

FeatureDeliriumDementiaDepression

OnsetAcute (Hours/Days)Chronic (Months/Years)Subacute

CourseFluctuating (Wax and Wane)Progressive declineWorse in mornings

AttentionImpaired (Can't focus)Usually NormalNormal

ConsciousnessAlteredClearClear

Key CauseUTI, Meds, InfectionAlzheimer's, VascularLife events, chemical

Delirium is a medical emergency. If grandpa suddenly starts talking to people who aren't there, check for a UTI, pneumonia, or a new medication.

Pseudodementia: Sometimes, profound depression in the elderly looks like dementia. They have memory loss, but when you ask them a question, they say "I don't know" (giving up). A true dementia patient will try to make up an answer (confabulate).

IV. Bone Health: Osteoporosis

Osteoporosis is the "Silent Thief." It steals bone mass without symptoms until a hip fractures.

Screening: DEXA scan for all women >65.

The Score: We look at the T-score.

Normal: -1.0 or higher.

Osteopenia: -1.0 to -2.5.

Osteoporosis: -2.5 or lower.

The FRAX Tool: Used for patients with Osteopenia. It calculates the 10-year probability of a fracture. If the risk is high, we treat even if they don't have full-blown osteoporosis.

Treatment:

Bisphosphonates (e.g., Alendronate): First line. They inhibit osteoclasts (the bone eaters). Instruction: Must take on an empty stomach and sit upright for 30 mins to prevent esophageal burn.

Denosumab: A monoclonal antibody for those who can't tolerate bisphosphonates.

V. Advance Care Planning

Modern medicine can keep a body alive long after the mind and spirit have exhausted their reserves. This creates an ethical imperative to discuss "Goals of Care."

Healthcare Proxy (Durable Power of Attorney): The patient designates who makes decisions if they become incapacitated. This is the strongest legal document.

Living Will: A document stating what the patient wants (e.g., "No ventilator").

Palliative Care: Focused on symptom relief (pain, nausea, anxiety). It can be done alongside curative treatment.

Hospice Care: A specific insurance benefit for patients with a prognosis of <6 months. It focuses purely on comfort; curative treatments (like chemo) usually stop.

Immune System

Part I: Primary and Acquired Immunodeficiencies

1. The Pattern of Susceptibility: Constructing the Differential

Before we memorize syndromes, we must understand the "flavor" of the infection. The immune system has distinct branches, and pathogens are smart—they find the specific broken branch.

When you see a patient on Step 2, look at the type of bug.

The Humoral Defect (B-cell/Antibody issue): Antibodies are opsonins. They coat bacteria so phagocytes can eat them. Without antibodies (IgG, IgM, IgA), the body cannot handle encapsulated bacteria.

Think: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis.

The Clinical Picture: A child with recurrent otitis media, sinusitis, or pneumonia. It’s rarely a weird fungus; it’s usually a standard bacteria that just won’t go away.

The Cellular Defect (T-cell issue): T-cells are the generals. They direct the war against intracellular invaders. When T-cells fail, the body is overrun by things that hide inside cells.

Think: Viruses (VZV, CMV, HSV), Fungi (Candida, Pneumocystis), and Mycobacteria.

The Clinical Picture: Failure to thrive, chronic diarrhea, and thrush in a persistent, scary way.

The Phagocytic Defect: If the neutrophils can't eat or kill, you get abscesses.

Think: Staphylococcus aureus, Aspergillus, Burkholderia.

The Clinical Picture: Skin infections without pus (sometimes), or deep tissue abscesses filled with catalase-positive organisms.

2. Humoral Deficiencies: When the Factories Shut Down

Let’s look at the specific B-cell disorders you will see on the exam.

A. X-Linked Agammaglobulinemia (Bruton’s) Imagine a factory where the machinery is broken. The gene BTK (Bruton Tyrosine Kinase) is defective. B-cells cannot mature. They never leave the bone marrow.

The Patient: Usually a baby boy. He was fine for the first 6 months because mom’s antibodies (transplacental IgG) protected him. Once those fade, the infections start.

Key Findings:

Absent tonsils and lymph nodes. (No B-cells means no germinal centers, which implies no lymph node swelling).

Flow cytometry shows CD19+ and CD20+ cells are essentially zero.

All Immunoglobulin levels (IgG, IgA, IgM, IgE) are low.

Management: You cannot fix the gene easily yet. You must replace what is missing. Intravenous Immunoglobulin (IVIG) is the lifeline. Live vaccines are absolutely contraindicated—giving a live polio vaccine to a Bruton’s kid is dangerous.

B. Common Variable Immunodeficiency (CVID) This is the "late bloomer" of immunodeficiencies. It often doesn't show up until the 20s or 30s.

The Mechanism: The B-cells exist (normal B-cell count), but they don’t differentiate into plasma cells. They don’t make antibodies efficiently.

The Patient: A young adult with recurrent sinusitis or pneumonia. But here is the twist: CVID loves autoimmunity. These patients often develop Autoimmune Hemolytic Anemia (AIHA) or ITP.

The USMLE Trap: Do not confuse this with Bruton’s. Bruton’s is a baby boy with no B-cells. CVID is an adult with normal B-cell numbers but low immunoglobulins.

2026 Perspective: We are increasingly using genomic sequencing to subclass CVID, allowing for targeted therapies beyond just "give IVIG."

C. Selective IgA Deficiency This is the most common primary immunodeficiency. Many people have it and don’t know it.

The Clinical Picture: Most are asymptomatic. Some have recurrent Giardia lamblia infections (because IgA protects mucosal surfaces like the gut) or sinopulmonary infections.

The Critical Safety Alert: You must be careful with blood transfusions.

Why? These patients have no IgA. Their body sees IgA as a foreign invader. They might make anti-IgA antibodies.

The Scenario: An IgA-deficient patient gets a standard blood transfusion (which contains small amounts of donor IgA). The patient’s anti-IgA antibodies attack the donor blood.

Result: Anaphylaxis.

Management: If they need blood, you must order "IgA-deficient" or "washed" red blood cells.

3. Cellular and Combined Disorders: The Emergency Room of Immunology

A. DiGeorge Syndrome (Thymic Aplasia) This is a developmental failure of the 3rd and 4th pharyngeal pouches. It’s a deletion on chromosome 22q11.2.

The Mnemonic (CATCH-22):

Cardiac defects (Tetralogy of Fallot, Truncus Arteriosus).

Abnormal facies.

Thymic hypoplasia (No T-cells).

Cleft palate.

Hypocalcemia (No parathyroids).

The Presentation: A newborn with tetany (seizures due to low calcium) or a heart defect. The immune issue (recurrent viral/fungal infections) is secondary but deadly if missed.

Diagnosis: FISH study for 22q11 deletion. Chest X-ray reveals an absent thymic shadow.

B. Severe Combined Immunodeficiency (SCID) This is the "Bubble Boy" disease. It is a pediatric emergency. Both B-cell and T-cell lines are non-functional.

Etiology: Several types exist. X-linked (IL-2 receptor mutation) is common. Adenosine Deaminase (ADA) deficiency is another.

The Patient: Severe failure to thrive, chronic diarrhea, and thrush. They get everything: bacterial, viral, and fungal infections.

Management:

Isolation: Reverse isolation immediately.

No Live Vaccines: This is lethal.

The Cure: Hematopoietic Stem Cell Transplant (HSCT). Without it, survival beyond year 1 is rare.

Current Frontier: Gene therapy for ADA-SCID is becoming a standard of care option, fixing the patient's own cells rather than finding a donor.

4. Phagocytic and Complement Disorders: When Cleanup Fails

A. Chronic Granulomatous Disease (CGD) Neutrophils have a "respiratory burst" where they use superoxide radicals to kill bacteria. In CGD, the enzyme NADPH oxidase is broken.

The Consequence: They cannot generate their own hydrogen peroxide to kill bugs. Interestingly, they can utilize peroxide produced by the bacteria against the bacteria—unless the bacteria has an enzyme called Catalase.

Catalase Positive Organisms: These neutralize their own peroxide, leaving the neutrophil weaponless.

The List: Staphylococcus aureus, Pseudomonas, Serratia, Nocardia, Aspergillus.

Diagnosis: The old test was Nitroblue Tetrazolium (NBT). The modern, accurate test is Dihydrorhodamine (DHR) flow cytometry.

Result: Decreased fluorescence means CGD.

B. Terminal Complement Deficiency (C5-C9) The complement system ends in the Membrane Attack Complex (MAC), which drills holes in bacteria.

The Specific Susceptibility: Neisseria.

The Patient: Recurrent meningococcal meningitis or disseminated gonorrhea.

Management: These patients need aggressive vaccination against Meningococcus.

5. HIV/AIDS: The Modern Management

This is perhaps the highest yield section for Step 2. The management of HIV has evolved from "watch and wait" to "test and treat."

A. Diagnosis: The Algorithm Gone are the days of Western Blot confirmation as a first line.

Screening: 4th Generation Ag/Ab Combo Assay. This looks for HIV antibodies AND the p24 antigen. It detects infection much earlier (within 14-20 days).

Confirmation: If positive, an HIV-1/HIV-2 differentiation immunoassay is performed.

Tie-breaker: If the differentiation assay is indeterminate, then you order an HIV RNA viral load (NAT).

B. Treatment Principles

Start Time: Immediately. The mantra is "Rapid Start." We do not wait for the CD4 count to drop. We do not wait for genotype results if the patient is ready (we start a high-barrier regimen).

The Regimen: Generally, two NRTIs (Nucleoside Reverse Transcriptase Inhibitors) + one Integrase Inhibitor.

Example: Tenofovir + Emtricitabine + Dolutegravir.

C. Opportunistic Infection (OI) Prophylaxis You must memorize the CD4 thresholds.

CD4 < 200: Risk of Pneumocystis jirovecii pneumonia (PJP).

Prophylaxis: TMP-SMX (Bactrim).

CD4 < 100: Risk of Toxoplasma gondii (if IgG positive).

Prophylaxis: TMP-SMX covers this too!

CD4 < 50: Risk of Mycobacterium avium complex (MAC).

Update: As of recent guidelines, if a patient is starting ART immediately, primary prophylaxis for MAC (Azithromycin) is often no longer recommended because ART restores immunity fast enough. However, for Step 2, be aware of the historical threshold, but prioritize ART.

D. Immune Reconstitution Inflammatory Syndrome (IRIS) Imagine the immune system "waking up" after ART. It sees the lingering bugs and goes into a rage.

Scenario: A patient starts ART. Two weeks later, their fever spikes and their chest X-ray looks worse.