Porphyria

Question 1

Define porphyria

Answer 1

Group of inborn errors of metabolism characterislzed by overproduction of porhyrins.

Question 2

Pathogenesis

Answer 2

Porphyrins are organic cyclical compounds found in many aspects of biological life; the most important in humans is haem, the ironcontaining ring structure found in haemoglobin, myoglobin, and all of the cytochromes.2 The haem biosynthetic pathway is most active in the liver and bone marrow. In the porphyrias, genetic defects cause deficiency of intermediary enzymes in this pathway (Fig. 1). All acute porphyrias have the potential to develop acute neurovisceral crises when a precipitating event occurs (Table 2). Precipitating factors increase the demand for haem in the liver, for example, by inducing the haemcontaining cytochrome P450 family of enzymes, which results in an increased flux through the pathway and accumulation ofsubstrate before the enzyme defect. All enzyme defects seen in the acute porphyrias result in the accumulation of 5-aminolaevulinic acid (ALA). In acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP), porphobilinogen (PBG) is also elevated and levels are used to diagnose acute crises.

Question 3

1st step in heam synthesis

Question 4

Second step

Question 5

3rd step

Question 6

4th step

Question 7

5th step

Question 8

6th step

Question 9

7th step

Question 10

8th step

Question 11

Triggers for neurovisceral crisis

Answer 11

Question 12

Acute crisis presentation

Answer 12

Question 13

Management of acute crisis

Answer 13

1. General measures
   Review all drugs and stop possible precipitants
   Treat intercurrent illness appropriately
   Manage infection aggressively, septic screen if ko cause found
   Avoid catabolic state(200g glucose per day or carb loading)
2. IV haem alginate
   Suppress hepatic production of ALAand other porphyria precursors
   3mg/kg(max 250mg) once daily for 3 consecutive days
   Iv infusion over 30minin larg vein or CVP
   Mix 100ml nS in glass bottle
   SE: irritant to veins, thrombophlebitis
3. Supportive measures
   Analgesic
   N&v management
   Mgx enxiety
   Treat insomnia
   Treat delirium
   Give b blocker and nitrate for HPT, tachy
   Correct Hyponatraemia
   Control seizures
   Ventilatory support if needed
   Monitor and support Neurological conditions
   Sedation
   Thromboprophylaxis

Question 14

General measures

Question 15

Direct treatment

Question 16

Supportive treatment

Question 17

Investigation

Answer 17

Question 18

Diagnosis

Answer 18

Increase urin porphobilinogens
Increase urine 5 aminolaevulinic acid
Blood and fecal sample
DNA study

Question 19

Anesthetic considerations

Answer 19

full history
Neurologic assessment
Peripheral Neuropathy
Autonomic instability
Avoid triggers
Anxiolysis
Avoid prolonged starvation
Iv dextrose saline to avoid caloric restriction
Unsuitable for day surgery( need postop monitoring)

Question 20

Drug considerations

Answer 20