Sickle cell disease

Question 1

What is the sickle gene?

Answer 1

Sigle missense mutation at codon 6, leading to GLu repaplaced by val (non polar and smaller)
HbS results

Question 2

What are the consequences of sickle cell gene on RBC?

Answer 2

Distrotion of RBC shape-polymerasition (initially reversible) with formation of OxyHbC-becomes irrevierible
ADherent, Rigid and Dehydrated (increase the OxyHbS)

Question 3

Where is sickle gene most common?

Answer 3

Africa-especially west, but can be found to India (Might have risen independently - natural selection stronk)
matches endemic malaria
One of most common genetic disease

Question 4

What is sickle cell disorder

Answer 4

SS aneamia (aneamia only for SS) and compoouns heterozygous states (SC, SB thalassemia)-genetically sumple (AR) but clinical heterogenous
Sickle cell disease encompaces all those variances

Question 5

What is the effects of Sickle cell?

Answer 5

Short cell lifespan-heamolysis-aneamia, gall stones, aplastic crisis with parovirus (usually benign, but bad in SS)
Aneamia is partially due to reduced erythropoetic drive as HbS is low affinity Hb

Blockage of microvasculature-tissue damage, necrosis, pain(main cause of hosp), dysfunction. Infartion most common in spleen, bones (dactylitis) joints (osteomyelitis) skin (ulcers)

damages lungs (hypertension, chronic damage), urinary tract ( papillary necrosis, renal failure) , brain (stroke), eyes (retinopathy)

Question 6

How does sickle cell disease cause microvasculature occlusion?

Answer 6

HbS form polymers in the cells and change the shape
Adherence to ICAM/VCAM and weird shape + rigidity causes blockages
Might also cause reduced NO bioavailability (SS cells scavenge it)

Question 7

What are the causes of SS disease scavenging NO?

Answer 7

It causes numerous vasculopathy, including Polumonary hypertension -and these people usually have bad prognosis

Question 8

How is the early clincal course of Sickle cell?

Answer 8

Can vary wildly, evem within the same famility
Symptoms are rare before 3-6 months-onset when swithc from fetal to adult Hb
Early-dactylitis, splenic sequestration, infections (s.pneumoniae)
Constant improvement of survival rates-like penicillin prophylaxis, help parents learn how to examine early staged
now most children live, but only till like 40/50

Question 9

What are types of sickle emergency?

Answer 9

Speptic shock
Neurological signs - stroke (heamorghagic/ischeamic)
hypoxia (PoO2 <92%)
Signs and symptoms of aneaia (Hb<5)
Priapism-painful and lasting boner (can lead to permanent erectile dysf

Question 10

What is acute chest syndrome with SSD?

Answer 10

Fever cought, chest pain, tachypnoae, chest pain
more common in SS>SS>SbThal
develop in vasculo occlusive crisis

Question 11

What is avascular necrosis of the femoral head in SSD? and osteomyelitis?

Answer 11

Ischeamic damage to head of femur-lose the ball part

ALso common osteomyelitis due to salmonella infetions (most common, then staph)

Question 12

What is stroke in SSD?

Answer 12

affects mostly SS -most common between 2-9 Y/o

Mostly middle cerebral and major arteries

Question 13

What are gallstones in SSD?

Answer 13

By 25 y/o, prevalence is 50%

Coiheritance of guilbert syndrome increases risks further (less efficient bilibubin conjugation)

Question 14

What are some laboratory features of sickle cell?

Answer 14

Hb low (6-8 g/dl), reticulocytes high (except in aplastic crisis)
Film-sickled, boat cells, target cells, Howel-jolly bodies

Question 15

What are the methods for sickle cell diagnosis?

Answer 15

Solubility test-in the precesnce of reducing agent-solubility decrease, solition become turbid -but doesnt differentiate between SS and SA
Can also do Hb EPS/HPCL (high performancy liquid chromatography)

Question 16

What are the general features of treatment options for sickle cell?

Answer 16

General measures-folic acid, penicilin prophylaxis, vaccination, monitor spleen size, transfusion for acute aneamia, acute chest syndr and stroke, prganancy care

Exchange transfusions for stroke/ACS
Heamotopoetic stem cell transplant-only for rare cases
Induction of HbF-hydroxyurea/carbomide and butyrate

Question 17

What are the treatment options for painful crisis of sickle cell?

Answer 17

pain relief (opiods, analgesia, NSAID, Pregabalin -but varies wildy between people, Most widely used is diamorphine), hydration, warmth, O2 is needed (need to find cause-PE0 -need to excluse infection (CXR and blood/urine cluture)

Question 18

What are the main causes of sickle cell painful crisis?

Answer 18

Hypxoia, psycho stress, dehyrdation Infections, exercsions, exposure to cold

Question 19

what are the main disease modifying treatments for SSD?

Answer 19

hydroxyCardbomide (increase HbF, leading to less problems), transfusions and Heamatopoetic stem cell transplant

Question 20

What are the indications for heamatopoetic inSSD?

Answer 20

Usually for children where hydroxyurea has failed and they have CNSissue or ACS

Question 21

What new therapy are underway?

Answer 21

sucessful gene thearpy has converted SS to AA

P-selectin inhbitor-mAb Crizanlizumab - reduce the adherence of SSRBC in microvasculature

Question 22

What is sicke cell trait?

Answer 22

HbAS
normal life epxentency, normal blood count-asually asymptomatic
rarely-painless heamaturia
Can be problem in aneastetis, high altitude and extreme exertions (can even cause sudden death if bad enough)