Pathophysiology and important points about Vitamin A !!

Pathophysiology and important points about Vitamin A !!

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GLUT Receptors and Aquaporins ( One liners for DNB)

Aquaporin Channels-

Aquaporin 0 – lens (fluid balance)

Aquaporin 1 – RBCs (osmotic protection)
PCT (urine concentration)
Ciliary epithelium of eye (aqueous humor production)
Choroid plexus (CSF production)
Alveolar epithelial cell (alveolar hydration)

Aquaporin 2 – Collecting duct (ADH activity)

Aquaporin 3 – Collecting duct (water reabsorption into blood)
tracheal epithelial cells

Aquaporin 4 – collecting duct duct (water reabsortion)
Ependymal cells (CSF balance)
Hypothalamus (osmotic function)
Bronchial epithelium

Aquaporin 5 – salivary gland (saliva production)
Lacrimal gland (tear production)

Aquaporin 6 – kidney

Aquaporin 7 – fat cells (glycerol transport out of adipocytes)
Testis n sperm

Aquaporin 8 – testis, pancreas, liver

Aquaporin 9 – adipose tissue, areas lacking BBB

Aquaporin 3, 7 n 9 are aquaglyceroporins

Mutation in aquaporin 2 is asso. with Hereditary Nephrogenic Diabetes Insipidus

Deficiency of aquaporin4 – Neuromyelitis optica (Devic’s dis), it resembles with multiple sclerosis

Deficiency of aquaporin 7 and 9 is associated with Obesity.

GLUT Receptors-

GLUT 1 – RBCs (other sites are placenta,brain, kidney, colon)

GLUT 2 – Liver (other sites are pancreatic beta cell, kidney, small intestine)

GLUT 3 – Brain, testis

GLUT 4 – Adipose tissue, Skeletal muscle, Heart muscle

GLUT 5 – Intestine, testis, kidney, sperm (for fructose)

GLUT 6 – Leukocyte, spleen

Phosphodiesterase Enzyme Inhibitors-

PDE1 inhibitor: Vinpocetine

PDE2inhibitor: EHNA

PDE3 inhibitor: Enoximone,milrinone,Amrinone

PDE4 inhibitor: Ibudilast,pentoxiffyline,cilomilast,

PDE5 inhibitor: Sildenafil, tadalafil and vardenafil,

NONSELECTIVE: Theophyllins

CONCEPT OF GENOMIC IMPRINTING AND DISEASES

We will try to understand concept of genomic imprinting by example of Prader Willi syndrome & Angelman syndrome.

Chromosome 15 q 11-13 have 2 sets of gene : PWS Region and AS gene.

A normal individual will have a pair of chromosome no 15 one from father and one from mother . PWS region of 15 q 11-13 is trancriptionally active only on the chromosome inherited from FATHER. These genes are transcriptionally inactive (imprinted) on the copy of chromosome 15 inherited from mother. SO THE PWS REGION ON CHROMOSOME SHOW MATERNAL IMPRINTING [ Kindly note that this process of gene silencing is called as imprinting and the transcriptionally inactive gene is said to be imprinted (ref : page 89 Medical Genetics elsevier 4thed)]

Also note that this process of imprinting in itself is not enough to cause a disease as PWS region is still functioning in a individual.

Then q arises how does PRADER WILLI SYNDROME occurs ??

PRADER WILLI will occur if PWS region gene are not present/functioning in a person.

So Prader Willi syndrome will occur if a gene deletion involving PWS region on chromosome15 is inherited from father. As only paternaly inherited PWS  gene is normally functional and maternal gene is already silent ( imprinted). So gene deletion on paternal ch 15 leads to absence of any functional copy of gene resulting in PRADER WILLI SYNDROME.

Other mechanism is that if a child inherits both copies of chromosome 15 from mother = UNIMATERNAL DISOMY , as in this situation also no functional copy of PWS gene is present.

So we get to conclusion that:

[1] PRADER WILL SYNDROME IS DUE TO

[a] INHERITENCE OF DELETION OF 15q11-13 FROM FATHER (70 % cases of PWS)*

[b] UNIMATERNAL DISOMY

[2] GENE RESPONSIBLE FOR PRADER WILLI SYNDROME ie PWS gene on 15q11-13 IS NORMALLY MATERNALLY IMPRINTED [ YES ITS TRUE 🙂 ]

by same explanation we will reach to conclusion that

[1] ANGELMAN SYNDROME IS DUE TO :

[a] INHERITENCE OF DELETION OF 15q11-13 FROM MOTHER

[b] UNIPATERNAL DISOMY

[2] GENE RESPONSIBLE FOR ANGELMAN SYNDROME ie AS GENE on 15q11-13 IS NORMALLY PATERNALY IMPRINTED [ YES ITS TRUE 🙂 ]

FEATURES OF BOTH SYNDROMES

[Q1] Not seen in Prader willi syndrome……
[A] short stature
[B] hypotonia
[C] obesity
[D] hypogonadism
[E] severe mental retardation

[Q2] which is not seen in Angelman syndrome…..
[A] seizure
[B] ataxic gait
[C] severe mental retardation
[D] hypogonadism

Ans :
[Q1] =Ans= [e] In prader willi mild to moderate mental retardation is seen and not severe one.

Moreover prader willi = short stature + hypotonia + small hands and feet + obesity + mild to moderate mental retardation + hypogonadism .

Note that severe mental retardation is a feature of Angelman syndrome.

[Q2]=Ans = [d]

NOTE ; EXAMPLE OF GENOMIC IMPRINTING
{1} PRADER_ WILLI ( 15q 11-13)
{2} ANGELMAN ( 15q 11-13)
{3} BECKWITH_WIEDMANN SYNDROME( 11p)
{4} RUSSELL_ SILVER SYNDROME (11p 15.5)

Q = HOW IS ISOCHROMOSOME FORMED ???? [ AIIMS MAY 2013]

ISOCHROMOSOME is formed by abnormal division of chromosome so that isochromosomes have either only two short arms or two long arms.

for eg if chromosome no 12 divides abnormaly ,2 isochromosomes r formed [i12p & i12q]

i12p =  isochromosome having short arm of chromosome only ,persons having this kayotype will lack genes which would have been present on long arm.

Now see the diagram to understand ….mechanism of formation of isochromosome

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now lets have a look over this ” new arrival ” at AIIMS MAY 2013

Q1] IF A CHROMOSOME DIVIDES PERPENDICULAR TO ITS NORMAL AXIS OF DIVISION THEN IT WILL FORM……[AIIMS MAY 2013]

[A] ACROCENTRIC

[B] SUBTELOCENTRIC

[C] ISOCHROMOSOME

ANS = [C] AS EXPLAINED AVOVE

NOTE : [1] Isochromosome formation frequently occours in X -chromosome [ iXp & iXq ]and some of genes will be absent in individuals with either iXp or iXq and they will show some of the phenotypes of  turner syndrome.

[2] isochromosome i12p is found in germ cell tumors.

other qs of aiims may 2013

AIIMS MAY 2013 QUESTIONS

1 KLUVER BUCY SYNDROME http://pguploads.com/2013/03/16/amygdal/

2. EYE Q = NHL OF ORBIT / METS TO ORBIT http://pguploads.com/2013/05/14/nhl-of-orbit-mets-to-orbit-aiims-may-2013/

3 . psychiatry ..jean piaget http://pguploads.com/2013/05/15/out-of-sight-is-not-out-of-mind-or-object-permanence-in-jean-piagets-development-theory-aiims-may-2003/

4. sudecks dystrophy http://pguploads.com/2013/05/15/reflex-symphathetic-dystrophy-cprs-i-sudecks-dystrophy-aiims-2013/

5 . isochromosome  http://pguploads.com/2013/05/14/q-how-is-isochromosome-formed-aiims-may-2013/

6 .seizure related qs in aiims 2013 http://pguploads.com/2013/05/14/seizure-related-qs-in-aiims-may-2013/

7. PSM Q’S http://pguploads.com/2013/05/16/psm-qs-aiims-may-2013/

MCQ ON PORPHYRIA

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ANS = C (SEE FIGURE BELOW)

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ANS =B (SEE FIGURE BELOW)

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ANS = D & E ( SEE FIGURE BELOW)

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ANS =E

In general enzyme inducers ppt porphyria so phenobarb , phenytoin , rifampicin will ppt porphyria.( SEE FIGURE BELOW)

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ans = E ( SEE FIGURE BELOW)

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ANS =D (SEE FIGURE OF Q2)

REFERENCE : HARRISONS 17ED PAGE 2434

HARRISON MANUAL OF INTERNAL MEDICINE 18 ED PG 1182