Q: What is the relevance of the name Hemolytic Uremic Syndrome ? 

A: Hemolysis --> Refers to microangiopathic hemolytic anemia (MAHA) due to RBC fragmentation in microthrombi. (In hemolysis, we see 8 key changes 6 increase 2 decrease which we can remember with the mnemonic "PUURLS HH" (High Pigmented gallstones, High Urobilinogen, High Unconjugated bilirubin, High Reticulocytes, High LDH, High schistiocytes, Low Haptoglobin and Low hemoglobin) 

 

Cause:
RBCs get mechanically sheared as they pass through platelet-rich microthrombi.

 

Uremia 

Refers to acute kidney injury caused by Shiga toxin–mediated endothelial damage.

Mechanism:

• Shiga toxin from E. coli O157:H7

• Binds Gb3 (globotriaosylceramide) receptor

• Inhibits 60S ribosomal subunit → ↓ protein synthesis

• Endothelial cell death

• Loss of antithrombotic surface

• Microthrombi formation in renal microvasculature

• ↓ Renal blood flow → ↓ GFR

• ↑ Creatinine and ↑ BUN

 

Q:What is the epidemiology of the HUS ? 

A: Typically in children 

 

Q: What is the pathophsyiology of HUS ?

A: STEC infection

↓
Shiga toxin release
↓
Binds Gb3 on renal endothelial cells
↓
Inhibits protein synthesis (60S ribosome)
↓
Endothelial cell death
↓
Loss of antithrombotic factors (↓ prostacyclin, ↓ NO)
↓
Platelet activation
↓
Microthrombi
↓
MAHA + thrombocytopenia (consumed in microthrombi) + AKI (decrease renal BF and decrease GFR due to microthrombi) 

 

 

Q: What is the triad of HUS ?
A: TRIAD = (1) Thrombocytopenia (due to platelet consumption microthrombi) (2) Microangiopathic hemolytic anemia
(due to microthrombi; decrease Hg)  (3) Kidney failure (increase creatinine due to decrease BF) 

 

 

Q: What is the differienting feature of the HUS ?

A: Triad + Blood Diarrhea 

 

Q: What are the coagulation studies in the HUS ? 

A: Normal PTT and PT Normal fibrinogenwhich helps to differentiate from DIC which involves the activationof the coagulation cascade  

 

Q: What is the tx of the HUS ?
A: Fluid, Dialysis if needed and RBC transfusion if severe anemia
 

 

Q: What should you avoid in the patients with HUS ?

A: Avoid ATB and Antimotility agents 

Antibiotics:

• Cause bacterial lysis

• ↑ Shiga toxin release

• ↑ Endothelial damage

Antimotility agents:

• Slow clearance of bacteria

• ↑ Toxin absorption

​

Q: What is another name for schistocytes?

A: Helmet cells

Explanation: They form when RBCs are mechanically sheared by fibrin strands/microthrombi in small vessels.

characterized by a concave, "bitten," or helmet-like appearance with pointed tips, caused by physical trauma in the circulation.

​

Q: What is a syndrome? 

A: A recognizable cluster of signs and symptoms that occur together due to a common underlying process.

 

Q: What does O157:H7 mean?

A: O antigen = part of the lipopolysaccharide (LPS) on the outer membrane, It’s the somatic antigen (heat-stable, structural component located on the cell wall )

H antigen = flagellar antigen

 

Q: Which population does atypical HUS occur in ?

A: Adults