Rapid Review·General Pathology
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INFLAMMATION
T2High yieldAcute Phase Reactants & ESR
P209–P210
Focus on
The panel of proteins IL-6 forces the liver to make, and why fibrinogen makes red cells fall faster.
Key takeaways
Acute-phase reactants
Acute-phase reactants are made by the LIVER and induced primarily by IL-6.
| Reactant | Direction | Function / Significance |
|---|---|---|
| C-reactive protein | ↑ | Opsonin; fixes complement; more specific than ESR |
| Ferritin | ↑ | Binds and sequesters iron to starve microbes |
| Fibrinogen | ↑ | Coagulation factor; coats RBCs → rouleaux → ↑ ESR |
| Haptoglobin | ↑ | Binds free hemoglobin; protects against oxidative stress |
| Hepcidin | ↑ | ↓ gut iron absorption (degrades ferroportin) and traps iron in macrophages → anemia of chronic disease |
| Procalcitonin | ↑ | Rises specifically in bacterial infections |
| Serum amyloid A | ↑ | Prolonged elevation → secondary (AA) amyloidosis |
| Albumin | ↓ | Downregulated to conserve amino acids for the positive reactants |
| Transferrin | ↓ | Internalized by macrophages to sequester iron |
| Transthyretin | ↓ | Prealbumin; also conserves amino acids |
Erythrocyte sedimentation rate
Erythrocyte sedimentation rate, the mechanism
RBCs normally repel each other via negative surface charges.- Products of inflammation, especially fibrinogen, coat the RBCs → ↓ negative charge → rouleaux (stacked-coin) aggregation → denser aggregates fall faster in the pipette → ↑ ESR.
- Everything on the list below is just an application of that one sentence: anything that helps stacking raises the ESR, anything that physically prevents stacking lowers it.
| Direction | Causes | The reason |
|---|---|---|
| ↑ ESR | Most anemias; infections; inflammation (giant cell/temporal arteritis and polymyalgia rheumatica, classically over 100); cancer (multiple myeloma, metastases); renal disease (ESRD, nephrotic syndrome); pregnancy | More plasma protein, especially fibrinogen and immunoglobulin, coating the RBC surface |
| ↓ ESR | Sickle cell anemia | The altered cell shape physically prevents stacking |
| ↓ ESR | Polycythemia | Excess RBCs dilute the aggregating factors |
| ↓ ESR | HF, microcytosis, hypofibrinogenemia | Too little fibrinogen, or cells too small to form tall stacks |
A woman with polycythemia has a markedly low ESR. What is the mechanism?
The excess RBCs dilute the aggregating factors (fibrinogen and other plasma proteins), so fewer rouleaux form and the cells settle more slowly.
How it's tested
A patient with longstanding rheumatoid arthritis develops a normocytic-to-microcytic anemia with ↓ serum iron, ↓ TIBC/transferrin, and ↑ ferritin. This is anemia of chronic disease, and the mechanism they want is IL-6-driven hepatic hepcidin release, which degrades ferroportin so iron cannot leave enterocytes or macrophages.
The trap is iron deficiency anemia, where ferritin is LOW and TIBC/transferrin is HIGH. The body is starving for iron rather than deliberately hiding it.
An elderly patient with a new temporal headache, jaw claudication, and vision loss has an ESR over 100, but the exam-relevant mechanism is that fibrinogen, an IL-6-induced acute-phase reactant, neutralizes the RBC surface charge to permit rouleaux.
The reverse trap: a sickle cell patient with an obvious infection has a normal or low ESR. The sickled cells physically cannot stack into rouleaux, so a normal ESR does not exclude inflammation in that patient.
Go deeper
First Aid "Acute phase reactants" table + "Erythrocyte sedimentation rate"; Pathoma Ch. 2. Anchor the up (CRP, ferritin, fibrinogen, hepcidin, SAA) vs down (albumin, transferrin) reactants — hepcidin is the link to anemia of chronic disease — and the rouleaux mechanism (fibrinogen neutralizes RBC charge → stacking → faster fall) with the low-ESR causes (sickle cell, polycythemia) that break the rule.
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