4.4 Normal vs Abnormal Physiologic Change

Quick Answer: Normal depends on age and physiologic state. Infants run faster hearts and lungs and lower blood pressures than adults. Pregnancy raises plasma volume and GFR, so a creatinine of 1.0 mg/dL is too high and preeclampsia is never normal. Older adults get isolated systolic hypertension, lower GFR, blunted fever, and atypical ACS; new fluctuating inattention is delirium, not instant dementia. Pubertal gynecomastia and irregular menses in the first 1–2 years after menarche are often physiologic — unilateral hard masses, delayed menarche, or hemorrhage are not.

Differentiating normal versus abnormal overall health and physiologic change is an official Domain II skill. The Test Content Outline also lists eight age groups (infant through frail elderly). The exam loves a finding that is reassuring at one age and an emergency at another. Your job is not to memorize every unpublished percentile. It is to know which direction is expected, when a variant is allowed, and which feature kicks the patient out of the normal lane.

Pediatrics: vitals, blood, murmurs, and pains

Heart rate and respiratory rate are higher, blood pressure is lower. A resting adult heart rate of 70 can be a preterminal infant. Use an age-based table (PALS/AAP), not a remembered adult range. Directional anchors the exam expects: neonates and young infants normally breathe in the 30s to 40s (and can be higher when crying); school-age children settle toward the 20s; adult-range bradycardia in a neonate is late and ominous. Blood pressure rises through childhood; a hypertensive-range adult number is not required before you call an infant hypotensive. Fever, pain, and fear raise heart rate — interpret the well-appearing, well-perfused child differently from the mottled one with the same number.

Physiologic anemia of infancy is expected. After birth, erythropoietin falls, fetal hemoglobin declines, and hemoglobin nadirs around 6–9 weeks in a term infant (often in a neighborhood of 9–11 g/dL) and earlier and lower in preterm infants. The infant is growing, feeding, and otherwise well, with a history that matches the timing. Kick-outs: a nadir that is too early or too deep, hemolysis (jaundice, dark urine, family history), blood-loss clues, or a toddler with a falling hemoglobin long after the physiologic window — that is iron deficiency or something worse, not lingering infancy physiology.

Still's murmur versus pathologic murmur. Still's murmur is the classic innocent musical or vibratory murmur: grade 1–2/6, lower left sternal border, louder when supine, softer when sitting or standing, no click, no thrill, normal splitting of S2, normal pulses, a thriving child. Pathologic clues: holosystolic or diastolic timing, grade 3 or louder, a thrill, a fixed split S2, diminished femoral pulses, cyanosis, poor feeding, or failure to thrive. Those features leave the innocent lane and need referral, not a six-month watch because it is probably Still's.

Growing pains versus inflammatory disease. Growing pains are bilateral, evening or nocturnal, in the legs, with a normal exam in the morning, no limp, no swelling, and no systemic signs. Inflammatory or serious bone-joint disease is morning stiffness, a limp, unilateral pain, joint swelling, refusal to bear weight, fever, back pain in a young child, or unremitting night pain that does not resolve with parental massage and time. The second cluster is investigate (infection, leukemia, juvenile idiopathic arthritis), not growing pains.

Pregnancy: expected hemodynamics — and what is never normal

Pregnancy is a high-flow, low-resistance state.

• Plasma volume rises on the order of 40–50%. Red-cell mass rises less, so a dilutional (relative) anemia is expected. That does not make a hemoglobin of 8 g/dL physiologic; it means a mild mid-pregnancy drop can be normal and a severe drop is still pathology (iron deficiency, bleed, hemolysis).
• GFR rises substantially (on the order of 50%). Creatinine falls. A creatinine that would look fine on a nonpregnant slip — 1.0 mg/dL is the usual teaching example — is too high in pregnancy and is AKI or chronic kidney disease until proven otherwise.
• Blood pressure falls in the second trimester (vasodilation) and rises back toward baseline in the third. A mid-pregnancy drop is expected. A rise to a hypertensive range after 20 weeks is not a return to normal.
• Preeclampsia is not a normal variant. New-onset hypertension after 20 weeks plus proteinuria or end-organ features (thrombocytopenia, rising creatinine, liver-enzyme rise, pulmonary edema, new headache or visual change, RUQ pain) is disease. It is not anxiety, not reflux, and not growing pains of pregnancy. Same-day obstetric evaluation is the implication.
• TSH interpretation changes. Use a pregnancy-specific interval. Undertreated hypothyroidism harms the pregnancy; overcalling a nonpregnant-normal TSH as fine is an interpretation error (section 4.3).

Supine hypotensive syndrome (aortocaval compression late in pregnancy) is physiology you fix by left-lateral tilt, not by calling the patient vasovagal and sending her home without a blood-pressure check sitting and in the left lateral position.

Older and frail adults: stiffness, silence, and acute brain change

Isolated systolic hypertension is the dominant older-adult phenotype because large arteries stiffen. Pulse pressure widens. This is common; it is not a reason to ignore systolic elevation as normal aging. Treat using current hypertension guidance and watch diastolic floor and orthostasis when you intensify therapy.

GFR declines with nephron loss and vascular aging. That expected drift does not make NSAIDs safe, and it does not make a sudden creatinine jump normal. Frail, low-muscle patients hide a low GFR behind a modest creatinine (section 4.3).

Fever blunts. Older and frail adults mount less fever and less leukocytosis. Infection presents as falls, anorexia, incontinence, or delirium. A normal temperature does not clear pneumonia or pyelonephritis.

Atypical ACS. The mechanism is still plaque rupture or supply-demand mismatch. The manifestation is often dyspnea, fatigue, epigastric discomfort, or acute confusion rather than textbook crushing pressure. Applying the young-male Hollywood script to an 84-year-old woman is how STEMIs are missed in primary care.

Delirium versus dementia. Dementia is chronic, progressive, and does not fluctuate hour to hour. Delirium is acute, fluctuating, and inattentive, usually from infection, medicines, electrolyte shifts, hypoxia, or urinary retention. A patient who knew her address last week and tonight cannot attend to your questions has delirium until you find the driver. Do not diagnose new Alzheimer disease at 2 a.m. and do not send delirium home as sundowning.

Frail elderly is a physiologic state (loss of reserve), not a synonym for older adult. The same UTI that is cystitis in a robust 70-year-old is sepsis-without-fever in a frail 70-year-old.

Adolescents: breast and menstrual physiology

Pubertal gynecomastia is common in boys around Tanner 2–3: bilateral, tender, disc-like tissue under the nipple, usually less than about 4 cm, no discharge, normal testicular volume, no androgen-deficiency signs. It often involutes over 6–24 months. Kick-outs that leave the physiologic lane: prepubertal onset, a hard eccentric unilateral mass, nipple discharge, small firm testes, rapid progressive enlargement, adult new-onset, or a drug/cannabis/anabolic story. Those features are test or refer, not a two-year observation.

Irregular menses are common for the first 1–2 years after menarche because cycles are often anovulatory. Reassurance requires the absence of hemorrhage and the presence of a timely menarche. Investigate: no menarche by 15 years (or no menses by 3 years after thelarche), cycles persistently shorter than 21 or longer than 45 days, soaking a pad or tampon every hour, passing large clots, symptomatic anemia, or signs of androgen excess / PCOS (hirsutism, severe acne, central obesity) or of outflow obstruction. Heavy anovulatory bleeding is not a character-building phase; it is a hemoglobin and a cause.

Headache, mood lability, and sleep-phase delay are common in adolescents; thunderclap, focal deficits, and suicidal ideation are not normal adolescent physiology.

Finding × age → normal variant vs investigate

Vignette

A 23-year-old woman at 24 weeks comes to establish primary-care prenatal comanagement. BP is 118/70 (it was 128/78 at her 8-week obstetric visit). Creatinine is 1.1 mg/dL. Hemoglobin is 10.6 g/dL. She has no headache, no visual change, and no RUQ pain.

Sort the physiology. The blood-pressure fall from the first trimester is expected mid-pregnancy vasodilation, not shock. The hemoglobin can be a modest dilutional change, but you still think about iron. The creatinine of 1.1 mg/dL is not normal — pregnancy should have raised her GFR and lowered creatinine. That number is a kidney problem, not a lab curiosity, and it is not preeclampsia by itself (her BP is not high). Two weeks later, if her BP is 152/94 with a new headache, that rise is preeclampsia physiology, not a third-trimester return to baseline. The FNP who knows which change is allowed will order the right test and make the right call.