SIckle cell crisis with pneumonia case

Case 7• 14 years male child come in emergency with

complain of– Acute abdominal pain since 12 hours– Acute hip joint pain since 2 days – High grade fever and breathlessness since 3 days

• Pediatrician examined patient. He asked for ICU admission and for following investigation

Laboratory InvestigationParameter Value Reference range

Haemoglobin 6.5 gm% 12 – 16 gm%

WBC 12000 4000-11000/cu.mm

Chest X-ray Left lower lobe opacity with pleural effusion

S.Total Billirubin 3.4 mg% 0.2 – 1.2 mg%

S.Direct Billirubin 0.8 mg% 0.1 – 0.2 mg%

S.Indirect Billirubin 2.6 mg% 0.2 – 1.0 mg%

S. ALT 40 IU/L 0 – 45 IU/L

S. Alkaline Phosphatase

950 IU/L 80 – 240 IU/L

S.LDH 2000 IU/L 150 – 350 IU/L

DiagnosisPneumonia with Sickle cell crisis

• Following Treatment is given• Oxygen inhalation• Inj ceftriaxone ………………IV 12 hourly• Inj Paracetamol …………….IV • Inj Normal Saline …………..IV • Inj Whole Blood …….. IV trasfusion• Tab Hydroxyurea 500 mg twice day orally

Questions

1.What is cause of increase in bilirubin in sickle cell crisis?

2.Explain biochemical mechanism of sickle cell crisis in low oxygenation conditions.

3.Explain biochemical basis of differential electrophoretic migration in Hb S and Hb A.

4.Explain biochemical mechanism of hydroxyurea in sickle cell crisis.

5.What is role of oxygen therapy is important in sickle cell crisis?

Overview

Cause of increase bilirubin

Complementary sticky patch on alpha chain due to deoxygenation.

Sticky patch due to replacement of glutamate by valine. Present on Hb S not Hb A.

Hb S under deoxygenated state

Deoxy Hb S combine with each other as shown in figure

Form a long chain that is responsible for sickle shape RBC

Chain can be broken by Oxy and Deoxy Hb A , Oxy Hb S and Hb F.

Biochemical basis of differential electrophoretic migration in Hb S and Hb A

Molecule of Hb S contains two normal α-globin chains and two mutant β-globin chains (βS), in which glutamate at position six has been replaced with valine

During electrophoresis at alkaline pH, Hb S migrates more slowly toward the anode (positive electrode) than does Hb A.

Hydroxyurea

It increases circulating levels of Hb F

Decreases RBC sickling

Decreased frequency of painful crises and reduces mortality

Biochemical mechanism of hydroxyurea

Thank you