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Thursday, October 13, 2016

HOW Hb S BECOMES A VILLAIN IN SICKLE CELL DISEASE (SCD) ❓


✔️ Inherited as Autosomal Dominant (Ⓜ️NEMO> Sickle Cell Disease is a SAD disease; S=SCD, AD=Autosomal Dominant)


✔️ A single DNA base change ( Beta chain) causes SCD


✔️ DNA base change is Adenine for Thymine & the resultant amino acid change is Valine for Glutamic Acid ( Ⓜ️NEMO> Addition of bases other than Thymine results in Valueless Goods )


✔️ Thus Hb S is produced. As Valine is hydrophobic, the deoxygenated Hb is less water soluble and gets precipitated & polymerized inside the RBC


✔️ This polymerization slightly reduces the overall affinity for O2; otherwise the affinity for O2 is same for Hb A and Hb S


✔️ These changes also make the RBS more rigid and contributes to sickling and microvascular occlusion


✔️ Regarding hypoxaemia, HbS will precipitate at a PO2 of 5–6 kPa (37-45 mm of Hg). As venous PO2 lies in this range, in case of homozygous individuals having only abnormal Hb will have continuous sickling


✔️ Patients with sickle cell trait experience sickling at much lower partial pressures (2.5–4 kPa / 19-30 mm of Hg )


✔️ Sickledex test produces a turbidity and becomes positive even with a very small amount of Hb S: so it CAN NOT differentiate between homo & heterozygous states


Reference: Smith T, Pinnock C, Lin T. Fundamentals of Anaesthesia, 3rd edn. Cambridge: Cambridge University Press, 2009; pp. 234–5 


#Anesthesia , #hematology , #medicine , #SickleCellDisease

Tuesday, October 11, 2016

INTRACRANIAL PRESSURE (ICP) & IT'S MEASUREMENT


🔸The ICP waveform is a modified arterial pressure tracing

🔸 It has 3 peaks: P1, P2 & P3

🔸 P1 is a result of transmitted pressure from choroid plexus

🔸 The amplitude of P2 changes with brain compliance. If compliance is poor, amplitude will be high ( can even exceed that of P1) and vice versa

🔸P3 represents the dicrotic notch

🔸 Lundberg (A) or Plateau waves are steep rise of ICP to over 50 mm of Hg and lasting for 5-20 minutes; then it falls abruptly. Are always pathological and indicates significantly reduced compliance

🔸 Lundberg (B) waves are oscillations occurring every 1-2 minutes where ICP rises to over 20-30 mm of Hg from baseline in a crescendo manner. They are supposed to be result of altered cerebral (B)lood volume and altered tone of cerebral (B)lood vessels 

🔸 Lundberg (C) waves are oscillations whose amplitude is less than that of B waves and are supposed to result because of interactions between cardiac and respiratory (C)ycles. They occur also in healthy individuals 

METHODS OF MEASUREMENT OF ICP

 Intraventricular catheter - ventriculostomy represents the "gold standard" for pressure measurement
 
✔️Normally placed in the frontal horn of lateral ventricle 

✔️Allows therapeutic CSF drainage 

✔️Creates a pathway for infection 

✔️Potential for accidental venting of CSF

✔️Possible subdural haemorrhage or upward brain herniation 

✔️ Catheter obstruction & ventricular haemorrhage may occur 

 Subdural bolt 

✔️ "Richmond Screw" or "Leeds device" inserted through a burr hole & an opening in the dura & arachnoid remains intact
 
✔️connects via a fluid couple to a transducer 

✔️ less invasive 

✔️ may underestimate high ICP and damping is a problem

 Subdural catheter 

✔️ Usually subdural space over frontal lobe of non-dominant hemisphere is selected
✔️ Prone to signal damping and calibration drift 

✔️ Potential risk of infection 

✔️ Doesn't require penetration of brain tissue

 Intracerebral transducer 

✔️Inability to check zero calibration & drain CSF 

✔️ Risk of infection

✔️Less reliable

🔸The incidence of infection ~ 2-7% with monitoring ≥ 5 days

🔸The risks are slightly greater with dural penetration 

🔸The zero reference point of the transducer is usually taken as the external auditory meatus 

🔸 Rather than the waveform type, the important factors appear to be the degree and duration of ICP elevation

A BIOPIC ABOUT THYROXIN



🚶🏻Tyrosine derived from thyroglobulin is combined with iodine to produce T3 & T4 (Thyroxin)

🚶🏻T3 is 5 times more active than T4, though T4 is produced in larger amounts 

🚶🏻'ACTIVITIES OF TSH'

✔️ Increase the size & number of thyroid gland cells
✔️ Increase iodide binding
✔️ Increase the release of thyroglobulin into the colloid of the gland
✔️Increase pinocytosis of colloid by the thyroid cells
✔️Increase hormone production 
✔️ Increase release of already produced hormone from the bound thyroglobulin and into the bloodstream 

🚶🏻In bloodstream the hormones are 99% protein bound. 

🚶🏻Thyroxin Binding Globulin (TBG) has the greatest affinity; but Albumin has the greatest capacity for binding the hormones. Thyroxine-binding prealbumin (TBPA) also bind them

🚶🏻REGULATION OF HORMONAL ACTIVITY

✔️ For regulation of the hormonal levels, the negative feedback is mediated by the unbound free fraction 
✔️ Stress inhibits production 
✔️ Warmth decreases production 
✔️ Cold increases production 
✔️ Glucocorticoids, dopamine & somatostatin inhibit TSH secretion

Reference: Smith T, Pinnock C, Lin T. Fundamentals of Anaesthesia, 3rd edn. Cambridge: Cambridge University Press, 2009; p. 474 .

#Thyroid , #Thyroxin , #Medicine , #Physiology