Chronic Disease Anemia

Before diving into lead's effects on heme synthesis, understand how chronic disease blocks iron utilization.

Iron Trapped: The Problem

In chronic disease (SLE, RA, infection), the body conserves energy. Iron is in the bone marrow BUT isn't being used.

Lab Differentiator

Chronic Disease Anemia
Ferritin: HIGH | TIBC: LOW | Serum Fe: Normal/Low
Iron Deficiency Anemia
Ferritin: NEVER normal/high | TIBC: NEVER low | Serum Fe: LOW
KEY: Ferritin Differentiates
HIGH ferritin → chronic disease (iron stuck in storage)
LOW ferritin → iron deficiency (body used all available iron)

Lead Poisoning: Heme Synthesis Blocker

Lead blocks heme synthesis by inhibiting two critical enzymes. Master the mechanism, master the boards.

Clinical Picture

Who: Children eating peeling paint (pre-1970)

Impact: Irreversible neurobehavioral dysfunction, delayed language

Classic clue: Basophilic stippling on blood smear

Enzymatic Blocks

Lead inhibits TWO enzymes:

1. Delta-ALA Dehydratase (2nd enzyme) → Blocks early synthesis
2. Ferrochelatase (last enzyme) → Can't add iron to porphyrin rings

Best Lab Test

Free Erythrocyte Protoporphyrins (FEP)
EXTREMELY HIGH - best test for lead exposure

Visual Hook: Basophilic Stippling

Porphyrin Rings Stuck on RBCs
Speckled appearance = diagnostic clue

Blood Lead Level: Management Protocol

No safe level exists. Drag the slider to explore management at each severity.
Blood Lead Level (μg/dL)
<55-1415-4445-69>70
— Select level —
Drag slider to see protocols

Chelation Agents

Drug Mechanisms
DMSA: Water-soluble, CANNOT cross BBB (useless for CNS lead)
EDTA: Binds 2+ charges (Ca,Fe,Pb,Cu,Mg) - risk of 5 deficiencies
BAL: Binds Pb+As, crosses BBB
Penicillamine: Chelates Cu+Pb

Critical Pearl

NO CHELATION for 5-44 μg/dL

Answer: remove from source, recheck in 6 months

Porphyrias: Diagnostic Decision Game

Which porphyria? Follow clinical clues to eliminate diagnoses.

Diagnostic Tree

SKIN symptoms (blisters, photosensitivity)?
Onset in infancy (<1 year)?
5 Ps present (pain, neuropathy, psych, pink urine, precipitated by drugs)?
Porphyria Cutanea Tarda (PCT)

Enzyme: Uroporphyrinogen decarboxylase

Onset: >1 year

Sx: Skin blisters from sun

Tx: Avoid light, phlebotomy, anti-malarials, Vit D

Erythropoietic Protoporphyria (EPP)

Enzyme: Ferrochelatase (same as lead block!)

Onset: <1 year

Sx: Light + rings = BURNS

MCC death: Skin infections

Acute Intermittent Porphyria (AIP)

Enzyme: Uroporphyrinogen I Synthase

Inheritance: Autosomal dominant

Classic: 5 Ps

Tx: IV saline, glucose, hematin, opiates

Most Common Causes of Intellectual Disability

Know the top 3 and their distinguishing features for board success.
#1 FETAL ALCOHOL SYNDROME

Smooth philtrum | #1 preventable cause today

#2 FRAGILE X SYNDROME

X-linked | Large ears/pill head (before puberty) | Macroorchidism (after)

#3 DOWN SYNDROME

Trisomy 21 | Upslanting palpebral fissures | Single palmar crease

Historical Note
Lead WAS #1 preventable before 1970s. Now: FAS, then lead regulations.

Hardy-Weinberg: Carrier Risk

Family history? Use Punnett square. No history? Use Hardy-Weinberg.

With Family History

Both parents carriers (Aa × Aa):

AA (25%) | Aa (50%) | aa (25%)
Of unaffected: 2/3 are carriers

No Family History

Hardy-Weinberg Equation:

p² + 2pq + q² = 1
If rare: aa = q², Carrier = 2pq
When to Use
Family history → Punnett square
No history → Hardy-Weinberg

Study Quiz

Test your knowledge. Wrong answers explain like a friend.