Sickle Cell Anemia

The Sickle Cell Anemia is a autosomal recessive disorder caused by a change in the 6 codon of the B-globin gene from A to T, results in a modified hemoglobin structure. The results is Hemoglobin S which polymerizes under low oxigen conditions, causing distortion of red blood cells leading to the associated clinical phenotype.

               Thr      Pro    Glu     Glu    beta A chain
               ACT  CCT   GAG  GAG   beta A gene
codon #     4        5         6         7
               ACT   CCT   GTG  GAG   beta A gene
               Thr       Pro     Val     Glu    beta A chain
The mutation in the gene coding for the B-chain of hemoglobin results in RBCs assuming a sickle shape when deoxygenated which them precipitate out of circulation and may occlude the microvasculature.

Mutation in both B-chain define the Sickle Cell disease, a single affected chain is Sickle cell trait.

HbS mutation is a single amino acid replacement in B-chain, substitution of normal glutamic acid with Valine. Low oxigen or dehydration precipitates sickling. Heterozygotes (sickle cell trait) are relatively malaria resistant.
Complivation in Homozygotes include aplastic crisis, due to parvovirus B19 infection, autosplecnectomy, inrease risk of encapsulated organism infection, Salmonella osteomyelitis, painful crisis, and splecnic squestration crisis.
Acute chest pain due to occlusion of bone marrow can cause a fat embolus to the lungs, resulting in hypoxemia anf possibly cardiovascular collapse.
8% of African-Americans carry the HbS trait, 0,2 % have the disease.
Sickled cells are crescent-shape RBC.
"Crew cut" in skull x-ray due to marrow expansion from increase erythropoiesis.
New-Born initially asymptomatic owing to high HbF and low HbS

Therapic for SCA include Hydroxyurea and bone marrow transplantation.
Because Ribavirin may cause a hemolytic anemia, it should be avoided in pte with hematologic disorder such as Sickle cell anemia and Thalasemia major.

retrieved from: First Aid for the USMLE step 1 2016, First Aid for Basic Sciences and General Princeples 2012.

Miscellaneous Echo finding (brief notes)

Ehlers-Danlos Syndrome:

 A heterogeneous group of connective tissue disorders with simple Mendelian inheritance. The cardinal manifestations of EDS are hyperextensible (stretchy) skin, hypermobile joints and easy bruising.

Echo/Doppler: Aortic root dilation, sinus de Valsalva aneurysm, Dilation of the proximal innominate artery, MVP, AVP, VSD, ASD, Tetralogy of Fallot, Aortic coarctation, Bicuspid AV, and Dextrocardia.

Fabry’s Disease:

          An X-linked recessive inborn error of glycosphingolipid metabolism.

          Echo/Doppler: MVP, increased LV wall thickness/mass, Aortic root dilation, MR, diastolic dysfunction.

Friedreich’s Ataxia:

          Cardiac abnormalities are a characteristic feature of the autosomal recessively inherited spinocerebellar degeneration known as FA, which is the most common hereditary ataxia.

          Echo/Doppler: Concentric Hypertrophy, Globally decreased LV systolic function, EF and FS. Increased left Atrial dimension.

Glycogen storage disease:

          A group of inheritable disorders of glycogen metabolism, resulting from specific enzymatic defects; Pompe’s disease (GSD type IIa) is a classic form of infantile GSD and is autosomal recessive.

          Echo/Doppler: severe thickness of the IVS, free wall and LVPW with a tumor-like appearance of the papillary muscles with small LV cavity. Poor global LV systolic function.

Holt-Oram (Heart-Hand) Syndrome:

          An autosomal dominant syndrome characterized by skeletal abnormalities and congenital cardiac defects.

          Echo/Doppler: ASD (ostium secundum), dilation of the right heart and paradoxical motion of IVS consistent with RVOL. VSD (trabecular type), may present with complex congenital heart disease/vascular malformations, Nonobstructive CM and MVP.

Loeys-Dietz syndrome (Aortic Aneurysm Syndrome):

          Autosomal dominant aortic aneurysm syndrome characterized by the triad of arterial tortuosity and aneurysms, hypertolerism and cleft palate. Aggressive arterial aneurysm (mean age of death 26 years of age), vascular disease may be widespread, and increased pregnancy related complications.

Marfan’s Syndrome:

          A hereditary condition of connective tissue, bones, muscles, ligaments and skeletal structures.  

          Echo/Doppler: Proximal aortic dilatation, multivalvular prolapse, dilated mitral annulus, MAC, left Atrial compression, LVVOL, AI, MR, aortic dissection (most common cause of death) and CAD.

Lyme disease:

          Caused by tick-borne spirochete, Borrelia burgdorferi, initial infection marked by rash, followed by weeks to months by involvement of other organ systems, including the heart, neurologic system and joints.

          Echo/Doppler: severe AV node block associated with syncope; DCM.

Noonan’s Syndrome:

          A inherited autosomal dominant manner and is characterized by congenital heart disease, short stature, abnormal facies and somatic features of Turner’s Syndrome but normal karyotype.

          Echo/Doppler: PV stenosis, Secundum ASD, VSD, PDA, and localized anterior septal hypertrophy.

Phen-fen:

          The appetite suppressants phentermine, fenfluramine and dexfenfluramine, alone or in combination, have been implicated as causing valvular disease; complication uncommon with less than 6 months of use.

          Echo/Doppler: thickened MV/Chordae Tendineae, thickened AV, mild or greater AR, mod or greater MR, pulmonary HTN.

 

Bibliography

Armstrong, W. F., & Ryan, T. (2010). Feigenbaum's Echocardiography. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins.

Reynolds, T. (2013). The Echocardiographer's Pocket Reference. USA: Arizona Heart Foundation.

PREDICTION OF INTRACARDIAC PRESSURES (Reynolds, 2013)

2-D echocardiography combined with cardiac Doppler may be utilized to predict intracardiac pressures.

Right Atrial Pressure (RAP)

v Normal 2 to 5 mmHg, to approximate the RAP, examine the IVC by 2-D and substitute one of the following values for the actual RAP.

Variable	Normal (0-5(3)mmHg)	Intermediate (5-10(8) mmHg)		High (15 mmHg)
IVC diameter	Less than 2.1 cm	Less than 2.1 cm	More than 2.1 cm	More than 2.1 cm
Collapse with sniff	More than 50 %	Less than 50 %	More than 50 %	Less than 50 %

 

Secondary indices of elevated RAP:

ü Restrictive filling

ü Tricuspid E/E’ more than 6

ü Diastolic flow predominance in hepatic veins (systolic filling fraction less than 55 %).

 

v Dilated hepatic veins with a dilated inferior vena cava suggest increased right Atrial pressure.

 

v A dilated coronary sinus (normal 4 to 8 mm as measured in the A4C with a posterior tilt) suggests increased RAP; it may be dilated also with persistent left superior vena cava, coronary artery AV fistula, anomalous hepatic vinous drainage to the left coronary sinus, and total anomalous pulmonary venous return or severe tricuspid regurgitation.

 

 

 

 

 

 

 

 

 

 

 

 

v In the absence of significant tricuspid regurgitation (TR), a right atrium that is increased in dimension especially when compared to the left atrium, suggests increased RAP.

 

v A right atrium maximal volume measured at end-systole of more than 45 +/- 14 cm3 suggests a mean RAP of more than 8 mmHg.

v A right Atrial maximal volume measured at end-diastole of more than 30 +/- 15 cm3 suggests a mean RAP of more than 8 mmHg.

v Interatrial septal deviation towards the left atrium may indicate increased RAP.

v A PW Doppler tricuspid valve E/A ratio of equal or more than 1.1 may indicate a mean RAP of > 8 mmHg, assumes the absence of right ventricular inflow tract obstruction.

 

v A dagger shaped CW tricuspid regurgitation velocity spectral display suggests increased RAP.

 

 

v A decreased right ventricular IVRT (normal 54 +/- 3.55 msec) suggests increased RAP.

 

 

 

v A patient with left heart disease and pulmonary hypertension may eventually develop elevated right heart pressures.

 

Bibliography

Reynolds, T. (2013). The Echocardiographer's Pocket Reference. USA: Arizona Heart Foundation.