AIIMS Q&A MAY 2015 By Dr Manish B Mandal
Copyright 2015 Dr Manish B Mandal Smashwords Edition
AIIMS MAY 2015 Q&A
1)Muscle not inserted on greater tuberosity a) Teres minor b) Supraspinatus c) Infraspinatus d) Subscapularis D
The supraspinatus, infraspinatus, teres minor and subscapularis muscles comprise the rotator cuff muscle group. The main role of these muscles is stabilization of the humeral head in the glenoid fossa. Tendons of teres minor, supraspinatus, and infraspinatus insert on the greater tuberosity of the humerus, and subscapularis tendon inserts on lesser humeral tuberosity. Actions of these muscles are internal rotation (subscapularis), external rotation (teres minor and infraspinatus) and early abduction from 0˚ to 30˚ (supraspinatus)7. The subacromial bursa lies between supraspinatus tendon and the acromion.
http://morphopedics.wikidot.com/supraspinatus-tendinitis 2) Card test done for
a) Lumbricals
b) Palmar interossei c) Dorsal interossei d) Adductor pollicis B
Ulnar Nerve (C7,8,T1) injury :
• M.C. site - Medial epicondyle, or a little more
distally where the nerve enters the
forearm b/w the two heads of flexor
carpi ulnaris
• Causes: - # of medial condyle
- During anesthesia
• S/S:
- Radial deviation of wrist on flexion
- Claw-hand deformity
- Paresthesia and sensory loss on hand
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21
A- Egawa’s Test – Dorsal Interossei
B- Card Test – Palmer interossei
C- Book Test - Adductor pollicis
(Froment,s sign)
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:Median nerve (C5,6,7,8,T1) injury:
• CAUSES
-- Crutch compression
- Sleep paralysis
- Penetrating trauma
- Shoulder dislocation
• S/S:
- Atrophy of the thenar
eminence
- Simian or ape hand
(d/t opponens pollicis)
- Benediction hand
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- Paresis of forearm pronation
- Paresis of distal flexion of the thumb
- Paresis of radial wrist flexion
- Impaired opposition of the thumb
- Paresis of flexion of the second and
to a lesser extent, the third fingers
Pen Test
– For Abductor pollicis brevis
http://www.aiimsnets.org/NeurosurgeryEducation/NeurosurgicalSpecialties/Peripheralnerve/Ner ve%20Injuries%20Diagnosis,%20Evaluation%20And%20Management_new/Nerve%20Injuries %20Diagnosis,%20Evaluation%20And%20Management.pdf
3) Which nerve doesn’t have a general visceral efferent a) Olfactory
b) Facial c) Oculomotor d) Glossopharyngeal A
It is possible to describe a cranial nerve in terms of its function and embryological origin, initially cranial nerves can be subdivided into being either:
• Motor (efferent)
And from there further categorization can occur.
---Motor (efferent) Cranial nerves
-Somatic motor (general somatic efferent) (III, IV, VI, XII)
These cranial nerves are so called because they innervate muscles derived from the occipital somites, such as the extra ocular and extrinsic tongue muscles.
-Branchial motor (special visceral efferent) (V, VII, IX, X, XI)
These are described as branchial because they specifically innervate muscles which are derived from the branchial arches during development (muscles of mastication, larynx, facial expression, pharynx and middle ear)
- Parasympatheic (general visceral efferent) (III, VII, IX, X)
These nuclei do not innervate striated muscle like the branchial and somatic, they instead provide preganglionic parasympathetic fibers to innervate glands, smooth muscle and cardiac muscle within the head, heart, lungs and digestive tract above the splenic flexure.
---Sensory (afferent) cranial nerves
-Visceral sensory
special visceral afferent- (VII, IX, X) general visceral afferent- (IX, X)
The name is related to the fact that it detects sensation from visceral organs.
They are divided into special visceral, referring to the rostral portion of the nucleus which contributes to the special sensation of taste. Whilst the general visceral portion is named as such due to this caudal portion receiving general sensory impulses such as cardiac, respiratory and GI inputs.
- General somatic sensory (general somatic afferent) (V, VII, IX, X)
These nuclei detect general sensation, such as touch, pain, vibration from the face, sinuses and meninges
- Special somatic sensory (special somatic)
(VIII)
This carries information from the special sensation of hearing and balance.
http://www.fastbleep.com/medical-notes/neuro-and-psych/2/95/610 4) Cranial nerve nucleus lying beneath the facial colliculus is
a) Facial b) Abducent
d) Trigeminal B
The abducent nucleus: This nucleus lies in the lower part of the pons, deep to the facial colliculus in the floor of the fourth ventricle. It is situated in the grey matter lining the floor of the fourth ventricle near the midline. The abducent nucleus is a motor nucleus and sends its attached nerve to supply the lateral rectus muscle.
https://www.kenhub.com/en/library/anatomy/cranial-nerve-nuclei
Overview of the Brainstem
The brainstem consists (from superior to inferior) of the midbrain, pons and the medulla oblongata. The midbrain is continuous, above, with the cerebral hemispheres. The medulla is continuous, below, with the spinal cord. Posteriorly, the pons and medulla are separated from the cerebellum by the
4th ventricle.
The brainstem has a ventral aspect (anterior surface) and a dorsal or posterior surface. Posterior surface
The posterior surface of the brainstem is formed by:
• the fasciculus gracilis (tracts from the posterior funiculus of the spinal cord) which ends superiorly as a rounded elevation called gracile tubercle
• the fasciculus cuneatus (also tracts from the posterior funiculus of the spinal cord) which ends superiorly as a rounded elevation called cuneate tubercle
These fasciculi and tubercles are at the lower half of the posterior surface of the medulla – thus the lowest portion of the brainstem (posteriorly).
At the midbrain level, the posterior surface of the brainstem is marked by four rounded swellings called the superior and inferior colliculi, with one pair (a superior- and an inferior colliculus) on each side of the midline, as well as a connecting ridge called the brachium. Most of the remaining part of the posterior surface of the brainstem, which includes the posterior surfaces of pons and the superior half of the medulla, is formed by the floor of the
4th ventricle.
The 4th ventricle is continuous, below, with the central canal, which traverses the lower part of the medulla, and becomes continuous with the central canal of the spinal cord. Cranially, the 4th ventricle is continuous with the cerebral aqueduct (of Sylvius), which passes
through the midbrain to connect the 3rd ventricle [which is a median cavity into which, the 1st and 2nd (lateral) ventricles open, through the interventricular foramen (of Monro).
The fourth ventricle also has a tent-shaped roof, cavity and lateral walls. However, the floor is the most related part to the cranial nerve nuclei.
The floor of the fourth ventricle, often called the rhomboid fossa because of its shape, is divisible into an upper triangular part formed by the posterior surface of the pons; a lower triangular part formed by the upper part of the posterior surface of the medulla; and an intermediate part at the junction of the pons and medulla. The intermediate part is prolonged laterally over the inferior cerebellar peduncle as the floor of the lateral recess. Its surface is marked by the presence of delicate bundles of transeversely running fibres. Those bundles are the striae medullares.
The entire floor is divided into right and left halves by a median sulcus. Next to the middle line, there is a longitudinal elevation called the medial eminence. The eminence is bounded laterally by the sulcus limitans. The region lateral to the sulcus limitans is the vestibular
area which overlies the vestibular nuclei (cranial nerve nuclei responsible for hearing and
balance). The vestibular area lies partly in the pons and partly in the medulla.
The pontine part of the floor shows some features of interest in close relation to the sulcus limitans and the median eminence. The uppermost part of the sulcus limitans overlies an area that is bluish in color and this area is called the locus coeruleus. Somewhat lower down, the sulcus limitans is marked by a depression, the superior fovea. At this level, the medial eminence shows a swelling, the facial colliculus.
The medullary part of the floor also shows some features of interest in relation to the medial eminence and the sulcus limitans. The sulcus limitans is marked by a depression, theinferior
fovea. Descending from the fovea, there is a sulcus that runs obliquely towards the middle
line. That sulcus divides the medial eminence into two triangles – the hypoglossal
trigone (which houses the cranial nerve nuclei called hypoglossal nuclei), medially; and
thevagal trigone (housing the vagal nuclei), laterally. Between the vagal trigone, superiorly and the gracile tubercle, inferiorly, there is a small area called the area postrema.
The lowest part of the floor of the fourth ventricle is called the calamus scriptorius, because of its resemblance to a nib. Each inferolateral margin of the ventricle is marked by a narrow
white ridge or taenia. The right and left taeniae meet at the inferior angle of the floor to form a small fold called the obex.
Ventral surface
The anterior surface of the brainstem is mainly marked by the left and right crus cerebri at the midbrain, the middle cerebellar peduncle at the level of the pons, and rounded elevations called olive and pyramid at the level of the medulla.
Within the brainstem, there is a remarkable number of tracts and grey matter. Along the entire length of the brainstem, there are areas not occupied by well-defined nuclei or nerve fibres, but consisted of a network of fibres within which scattered neurons are situated. Those areas are referred to as “the reticular formation of the brainstem”. These areas mainly occupy the dorsal part of the midbrain, pons and medulla. Such areas (reticular formation) are found at all levels of the central nervous system, and are functionally very important. At the level of the midbrain and medulla, there is a grey matter region called central grey
matter which surrounds the cerebral aqueduct and gives origin to some cranial nerve nuclei
including the mesencephalic nucleus of the trigeminal nerve. Most of the cranial nerve nuclei that migrated from their original position (in relation to the floor of fourth ventricle) during embryonic development are situated in this grey matter region (central grey matter).
Introduction
The cranial nerve nuclei are aggregate of cells (collection of cell bodies). Attached to these cell bodies are fibres called cranial nerves (bundles of axons). These nuclei are
either sensoryor motor but never both. However, cranial nerves can be sensory, motor or mixed
nerves(when they have both sensory and motor functions).
The cranial nerve motor nuclei are further grouped according to their targets, that is, where their axons (attached cranial nerves) are sent or structures they innervate. Hence the cranial nerve nuclei with motor functions can be grouped according to the following functional components to which their fibres belong:
• General Somatic Efferents (GSE)
• Special Visceral Efferents (SVE)
• General Visceral Efferents (GVE)
Similarly, the cranial nerve sensory nuclei are grouped according to the information they receive, which constitutes the functional components to which their attached nerves belong. These functional components are:
• General Somatic Afferents (GSA)
• General Visceral Afferents (GVA)
• Special Visceral Afferents (SVA)
The first cranial nerve (olfactory nerve – CN I) does not originate from a cranial nerve nucleus. CN 1 originates from the olfactory bulb, which is a structure located in the forebrain and controls olfaction. The second cranial nerve (optic nerve – CN II) originates from the lateral geniculate nucleus [(lateral geniculate body or lateral geniculate complex) – which is a relay centre in the thalamus for the visual pathway], the pulvinar, and the superior colliculus [the pulvinar and superior colliculus are also part of the primary visual centres, and from those three structures, fibres (CN II) connect the ganglionic cells of the retina to coordinate and interpret visual impulses].
In the brainstem, there are about 18 cranial nerve nuclei comprising of 10 motor cranial nerve nuclei and 8 sensory cranial nerve nuclei. The functions of those cranial nerves are suggestive of the functions of the parts of the brainstem they are located. For example, the midbrain is involved in eye movement control and houses the oculomotor and trochlear nuclei which also have these functions. The pons control breathing, signal relay, and contains the trigeminal, abducens and facial nuclei.
In summary therefore, cranial nerve nuclei are either motor (efferent) or sensory (afferent), and both category can be somatic or visceral.
Development
During embryonic development, the cranial nerve nuclei related to the various components – GSE, SVE, GVE, GSA, SSA, GVA and SVA, are arranged in vertical rows called columns in a definitive sequence in the grey matter related to the floor of the fourth ventricle. Each half (along the median sulcus) of the floor of the fourth ventricle is divided into a medial part called the basal lamina, and a lateral part called the alar lamina by the sulcus limitans.
The Efferent nuclei (motor nuclei) lie in the medial part, while the Afferent nuclei (sensory nuclei) lie in the lateral part – alar lamina. In both the medial and lateral parts, the visceral nuclei [special visceral (branchial) effernt, general visceral efferent, general visceral afferent, and special visceral afferent] lie nearer to the sulcus limitans than the somatic nuclei [GSE, GSA, and SSA]. Therefore, from the midline (median sulcus of the fourth ventricle) to the lateral aspects, the sequence of nuclear column is:
1. GSE - lying closest to the median sulcus 2. SVE - lying next to the GSE
3. GVE - lying farthest from the median sulcus but next to the sulcus limitans
All of the above listed three nuclear columns are in the medial part (basal lamina) of the floor of the 4th ventricle.
On the other side of the sulcus limitans – that is the lateral part (alar lamina), the sequence is:
1. GVA - lying next to the sulcus limitans 2. SVA - lying next to GVA, laterally 3. GSA - lying next to the SVA and finally
4. SSA - lying farthest away from the sulcus limitans, laterally
As development continues, parts of those columns disappear from their position in relation to the floor of the fourth ventricle, so that each of the no longer extends the whole length of the brainstem, but is represented by one or more discrete nuclei. Some nuclei retain their original positions in relation to the floor of the fourth ventricle, but some others migrate deeper into the brainstem.
In the descriptions that follows, the cranial nerve nuclei originating from each of these columns, as well as their definitive positions in the brainstem are outlined.
Gross Anatomy
General Somatic Efferent (Motor) Nuclei
The general somatic efferent column consists of the following nuclei that supply striated (skeletal) muscles of somatic origin.
1. The oculomotor nucleus: This nucleus is located in the upper part of the midbrain at the
level of the superior colliculus. The oculomotor nuclei (left and right sides) form a single complex that lies in the central grey matter, ventral to the cerebral aqueduct (of Sylvius). The oculomotor nucleus sends fibres (oculomotor nerve) to supply
thesuperior, medial and inferior rectus, inferior oblique and levator palpebrae superioris muscles.
2. The trochlear nucleus: The trochlear nucleus is located in the lower part of the midbrain
at the level of the inferior colliculus. The nucleus lies anterior to the cerebral aqueduct in the central grey matter. Since the trochlear nucleus is a motor nucleus, it sends fibres to innervate the superior oblique muscle.
3. The abducent nucleus: This nucleus lies in the lower part of the pons, deep to the facial
colliculus in the floor of the fourth ventricle. It is situated in the grey matter lining the floor of the fourth ventricle near the midline. The abducent nucleus is a motor nucleus and sends its attached nerve to supply the lateral rectus muscle.
4. The hypoglossal nucleus: The hypoglossal nucleus is situated near the midline and
below the hypoglossal trigone (or triangle) in the floor of the fourth ventricle of the upper medulla. It is an elongated column extending into both the open and closed parts of the medulla. Fibres from this nucleus are motor, and they innervate the muscles of the tongue.
Special Visceral Efferent (Motor) Nuclei
These nuclei are also called Branchial Efferent or Branchiomotor nuclei. They supply striated (skeletal) muscles derived from the branchial arches.
1. The motor nucleus of the trigeminal nerve: This cranial nucleus lies in the upper part of
the pons, in the pons' dorsal part. It is situated in the lateral part of the reticular formation, medial to the main sensory nucleus of the trigeminal nerve. The motor nucleus of trigeminal nerve innervates the mastication muscles, mylohyoid muscle and tensor palati.
2. The nucleus of the facial nerve: This nucleus lies in the lower part of the pons, deep and
lateral to the facial colliculus, and occupies a position similar to that of the motor nucleus of the trigeminal nerve, because the spinal nucleus and tract of the trigeminal nerve lie lateral to it, as seen in figure 8 above. The facial nerve nucleus sends its nerve to the lacrimal gland for lacrimal secretion and salivary secretion.
3. The nucleus ambiguus: The nucleus ambiguus lies in the medulla. It forms an elongated
collumn lying deep in the reticular formation, both in the open and closed parts of the medulla. Inferiorly, it is continuous with the spinal accessory nucleus. The nucleus ambiguus is a composite nucleus and contributes fibres to
the glossopharyngeal, vagusand accessory nerves. General Visceral Efferent (Motor) Nuclei
The nuclei of this column gives origin to preganglionic fibres that contribute to the cranial parasympathetic outflow. These fibres end in peripheral ganglia. Postganglionic fibres arising in those ganglia (peripheral ganglia) supply the smooth muscles and glands. The nuclei from the GVE are as follows:
1. The Edinger-Westphal nucleus (Accessory Oculomotor nucleus): This nucleus lies in the
midbrain. It is closely related to the oculomotor complex. Fibres arising in this
nucleus pass through the oculomotor nerve, and relay in the ciliary ganglion to supply the sphincter pupillae and the ciliaris muscle (see the “Visual Pathway”).
2. The Salivary (salivatory) nuclei: The superior and inferior salivary nuclei lie in the dorsal
part of the pons, just above its junction with the medulla. They are located a little above the upper end of the dorsal nucleus of the vagus nerve. The superior salivatory nucleus sends fibres into the facial nerve and these fibres relay in the submandibular ganglion to supply the submandibular and sublingual salivary glands. The inferior salivary nucleus sends fibres into the glossopharyngeal nerve. Those fibres relay in the otic ganglion to supply the parotid gland. The parotid gland may also receive some fibres from the superior salivatory nucleus, through the submandibular ganglion.
3. The dorsal or motor nucleus of the vagus nerve (dorsal vagal nucleus): This cranial nerve
trigone in the floor of the fourth ventricle. When traced backwards, it extends into the closed part of the medulla where it lies in the lateral part of the central grey matter. Fibres arising fom this nucleus supply
the heart, lungs, bronchi, oesophagus,stomach, small intestine and large intestine up to the right two-thirds of the transverse colon. Those fibres end in ganglion (nerve plexuses) closely related to those organs – heart, lungs, stomach, etc. General and Special Visceral Afferent (Sensory) Nuclei
The general and special visceral afferent collumns are represented by:
1. The nucleus of theSOLITARY tract
2. The commissural nucleus of vagus 3. The gustatory nucleus
The nucleus of theSOLITARY tract is present in the medulla. Its cells (nucleus
ofSOLITARY tract) form an elongated column lying deep in the reticular formation. The upper part of the nucleus of theSOLITARY tract lies ventrolateral to the dorsal nucleus of the vagus (dorsal vagal nucleus). When traced backwards, it extends into the closed part of the medulla. There it lies dorsomedial to the vagal nucleus. The lower ends of the nuclei of the two sides fuse to form the commissural nucleus of the vagus.
The nucleus solitarius receives fibres carrying general visceral sensations through the vagus and glossopharyngeal nerves. Through those afferents, and through connections with the reticular formation, the nucleus of solitary tract plays an important role in reflex control of respiratory and cardiovascular functions.
Fibres of taste – special visceral afferent, carried by facial, glossopharyngeal and vagus nerves end in the upper part of the nucleus of the solitary tract. This upper part of the nucleus is referred to as the gustatory nucleus.
General Somatic Afferent (Sensory) Nuclei
These nuclei give rise to the following sensory nuclei:
1. The main or superior sensory nucleus: This nucleus lies in the upper part of the pons, in
the lateral part of the reticular formation. It lies lateral to the motor nucleus of the trigeminal. The superior sensory nucleus is mainly concerned in mediation of proprioceptive impulses, touch and pressure.
2. The spinal nucleus: The spinal nucleus is another sensory cranial nerve nucleus which
extends from the main nucleus (superior sensory nucleus) in the pons down into the medulla, and into the upper two segments of the spinal cord. The lower end of the spinal nucleus is continuous with the substantia gelatinosa of the spinal cord. The spinal nucleus receives general somatic sensations carried by the facial,
glossopharyngeal and vagus nerves. Functions of the spinal nucleus includes mediation of pain and thermal sensibility. The spinal nucleus is divisible (cranio-caudally) into three sub-nuclei, theoralis, interpolaris, and caudalis.
3. The mesencephalic nucleus: This is also called the mesencephalic nucleus of the
trigeminal nerve. It extends cranially from the upper end of the main sensory nucleus in the pons into the midbrain. In the midbrain, the mesencephalic nucleus lies in the central grey matter lateral to the aqueduct. Functionally, this nucleus appears to be similar to sensory ganglia of the cranial nerves, and to the spinal ganglia, rather than to afferent nuclei. The processes (dendrites) of the neurons of this nucleus are believed to carry proprioceptive impulses from muscles of mastication, and possibly also from muscles of the eyeballs, face, tongue and teeth. The mesencephalic nucleus is the centre for jaw jerk.
Special Somatic Afferent (Sensory) Nuclei
This column gives rise to:
1. The cochlear nucleus 2. The vestibular nucleus
There are two cochlear nuclei – dorsal and ventral cochlear nucleus. They are respectively positioned dorsal and anterior to the inferior cerebellar peduncle at the level of the junction between the pons and medulla. The two nuclei are continuous with each other, being separated only by a layer of nerve fibres.
The vestibular nucleus lies in the grey matter underlying the lateral part of the floor of the fourth ventricle. The vestibular nucleus is situated partly in the medulla and partly in the pons. Four distinct nuclei of the vestibular nucleus are recognized. These nuclei are themedial, lateral, inferior and superior vestibular nuclei. The lateral nucleus is also called theDeiter's nucleus.
Connections Of Some Cranial Nerve Nuclei
Column of motor nucleus of the trigeminal nerve, nucleus of the facial nerve, nucleus ambiguus, and oculomotor, trochear, abducent, hypoglossal nuclei
The nuclei of the GSE and SVE connect with the skeletal muscles, to which they send their nerves. Those nuclei (GSE and SVE) receive sensory fibres through which they also make connections with the cerebral cortex, the tectum (connections of vision and of hearing), vestibular nuclei (vestibular impulses), sensory cranial nuclei, the red nucleus and the reticular formation.
Connections of the cochlear nuclei
The dorsal and ventral cochlear nuclei are major parts of the partway of hearing. They receive fibres connecting them with the spiral ganglion and sends their attached fibres, some of which relay in the trapezoid body, before reaching the nucleus of trapezoid body and the superior olivary nucleus.
The vestibular nuclei are connected to the cerebellum to which they send and receive fibres. These nuclei also have connections with the spinal cord, through fibres, mainly, originating in the medial vestibular nucleus. These fibres descend in the fasciculus.
Connections of the nucleus of theSOLITARY tract
The nucleus of theSOLITARY tract receives fibres from the sensory ganglia of the seventh, ninth, and tenth cranial nerves, and mainly send fibres to the hypothalamus (solitario-hypothalamic tract), the thalamus and cerebral cortex.
Connections of the sensory nuclei of the trigeminal nerve
The main sensory nucleus of the trigeminal nerve and the spinal nucleus of trigeminal nerve, both receive fibres, through which, they connect with the trigeminal ganglion. These nuclei (main sensory and spinal nucleus) send fibres to the thalamus and cerebral cortex.
Clinical Aspects
Brain DeathThe combined developments of ventilatory machines and transplantation surgery have underlined the need for defining the criteria for making a correct diagnosis of brain death – the irreversible cessation of brainstem function. In comatose patients with irremediable structural brain damage due to a disorder that can lead to brain death, brainstem reflexes must be shown to be absent in order to establish brain death. The following are the criteria (anatomical basis) normally adopted:
• Fixed pupils, not reacting to light – testing midbrain function
• No corneal reflexes – testing pontine connections between trigeminal and facial nerve nuclei
• No vestibulo-ocular reflexes – testing the connections between the vestibular nerve and eye muscle nerves
• No gag reflex or response to bronchial stimulation by a catheter passed down the trachea – testing vagal connections in the medulla
• No motor responses in any cranial nerves on adequate nociceptive stimulation of any somatic area – testing for facial grimacing from pressure on the supraorbital margins
(connections between trigeminal and facial nerve nuclei) or on the bases of fingernails (connections between cervical spinal cord and facial nerve nuclei)
a) Inferior rectal vein b) Pararectal node c) Superior rectal vein A
The mesorectum is an important surgical and radiological structure. It contains the superior rectal artery and vein, and numerous lymphatics as well as rectal branches of the inferior hypogastric plexus. It is bounded by the mesorectal fascia, a distinct layer which separates the rectal fat from other pelvic fat.
http://ozradonc.wikidot.com/anatomy:rectum 6) Which of these is not a support of the uterus a) Urogenital diaphragm
b) Pelvic diaphragm c) Perineal body
d) Rectovaginal septum D
7) Reticular framework is present in all tissues except a) Thymus
b) Bone marrow c) Spleen
d) Lymph node A
• Ref= The Anatomical Record > • Vol 190 Issue 3 >
• Abstract
Electron microscopy of the normal human thymus demonstrates a supporting framework of epithelial-reticular cells with long branching cytoplasmic processes joined by desmosomes. In the interstices of the epithelial-reticular cell processes lie lymphocytes, macrophages, and rare myoid cells. Both small and large lymphocytes are evident. No desmosomes are observed between the lymphocytes and the epithelial-reticular cells. Macrophages are most numerous in the cortex where they often contain phagocytized nuclear debris. The possible functional significance of the above-described fine structural features is discussed.
http://onlinelibrary.wiley.com/doi/10.1002/ar.1091900310/abstract 8) What is the stage present in the oogonia at birth
a) Telophase I b) Prophase I B
month: primary germ cells arise in the cortical zone via mitosis of oogonia
clones, bound together in cellular bridges, that happens in rapid succession.
The cell bridges are necessary for a synchronous onset of the subsequent meiosis.
• With the onset of the meiosis (earliest onset in the prophase in the 12th week) the designation of the germ cells changes. They are now called primary
oocytes.
The primary oocytes become arrested in the diplotene stage of prophase I (the prophase of the first meiotic division). Shortly before birth, all the fetal oocytes in the female ovary have attained this stage. The meiotic resting phase that then begins is called the dictyotene and it lasts till puberty, during which each month (and in each month thereafter until menopause) a pair of primary oocytes complete the first meiosis. Only a few oocytes (secondary oocytes plus one polar body), though, reach the second meiosis and the subsequent ovulation. The remaining oocytes that mature each month become atretic.
The primary oocytes that remain in the ovaries can stay in the dictyotene stage up to menopause, in the extreme case, without ever maturing during a menstrual cycle.
• While the oogonia transform into primary oocytes, they become restructured so that at the end of prophase I (the time of the dictyotene) each one gets enveloped by a single layer of flat, follicular epithelial cells (descendents of the coelomic epithelium). (oocyte + follicular epithelium = primordial follicle).
http://www.embryology.ch/anglais/cgametogen/oogenese01.html
9) At which stage of maturation of the spermatocyte the assortment of maternal and paternal chromosomes takes place
a) Spermatogonia to primary spermatocyte b) Primary to secondary spermatocyte c) Secondary spermatocyte to spermatids d) Spermatids to spermatozoa
B
10) Not a branch of external carotid artery a) Transverse cervical A.
b) Lingual A.
c) Superior thyroid A. d) Ascending pharyngeal A. A
11) All are derived from Mesonephros except a) Glomerulus
b) Paraoopharan c) Vas deferans d) Epididymis
A
The urogenital system arises during the fourth week of development from urogenital ridges in the intermediate mesoderm on each side of the primitive aorta. The nephrogenic ridgeis the part of the urogenital ridge that forms the urinary system. Three sets of kidneys develop sequentially in the embryo: The pronephros is rudimentary and nonfunctional, and regresses
completely. The mesonephros is functional for only a short period of time, and remains as
the mesonephric (Wolffian) duct. The metanephros remains as the permanent adult kidney. It develops from the uteric bud, an outgrowth of the mesonephric duct, and the metanephric
mesoderm, derived from the caudal part of the nephrogenic ridge.
Urine excreted into the amniotic cavity by the fetus forms a major component of the amniotic fluid. Urine formation begins towards the end of the first trimester (weeks 11 to 12) and continues throughout fetal life.
The kidneys develop in the pelvis and ascend during development to their adult anatomical location at T12-L3. This normally happens by the ninth week.
Table 12 - Adult Derivatives of Embryonic Kidney Structures
Embryonic Structure Adult Derivative
Ureteric bud (metanephric
diverticulum) UreterRenal pelvis
Major and minor calyces Collecting tubules
Metanephric mesoderm Renal glomerulus +
capillaries
Bowman’s capsule
Proximal convoluted tubule Loop of Henle
Distal convoluted tubule Urinary Bladder
The urinary bladder develops from the upper end of the urogenital sinus, which is
continuous with the allantois. It is lined with endoderm. The lower ends of the
metanephric ducts are incorporated into the wall of the urogenital sinus and form
the trigone of the bladder. The connective tissue and smooth muscle surrounding the
bladder are derived from adjacent splanchnic mesoderm.
The allantois degenerates and remains in the adult as a fibrous cord called the urachus
(median umbilical ligament).
http://www.med.umich.edu/lrc/coursepages/m1/embryology/embryo/11urinarysyste m.htm
12) Microvilli are not present in a) Duodenum
b) Gall bladder c) PCT
d) Collecting duct D
13) In the following picture, wave B represents – [PICTURE] EEG shows high amplitude, low frequency waves as compared to waves A & C and EOG & EMG are nearly flat when compared to A. In C also they are flat.
a) REM b) NREM
c) Quiet wakefulness d) Awake
B
EEG shows high amplitude, low frequency waves as compared to waves A & C and EOG & EMG are nearly flat when compared to A. In C also they are flat.
14) In the following diagram left ventricular pressure is nearly equal to diastolic BP at which number [PICTURE]
a) A b) B c) C d) D
(PIC NOT AVAILABLE)
15) If the interstitial hydrostatic pressure is 2 mm Hg, interstitial oncotic pressure is 7 mmHg and capillary hydrostatic pressure is 25mmHg, what should be the capillary oncotic pressure to allow a net filtration pressure of 3 mm Hg
a) 21 b) 27 B
GFR
If we disregard any oncotic pressure in the Bowman's capsule, we have in effect, three pressures to consider: glomerular hydrostatic pressure, glomerular oncotic pressure, and Bowman's capsule hydrostatic pressure. These can be expressed as a formula that will tell us the amount of hydrostatic pressure pushing fluid out of the glomerulus:
Net glomerular pressure equals:
Glomerular hydrostatic pressure minus [glomerular concotic pressure + Bowman's capsule hydrostatic pressure]
In order to measure the glomerular filtration rate, we must add to this measurement an estimation of glomerular permeability, and surface area – that is, how many functioning nephrons are available in the body for filtration, and how effectively the glomeruli filter fluid. A normal glomerular filtration rate is around 125mls/min, and this measurement is used to determine, and to classify, kidney function.
http://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/gfr/6.html
Net Filtration Pressure (NFP): NFP = HPg - (OPg + HPc)
Glomerular Hydrostatic Pressure: (HPg) is essentially glomerular blood pressure (55
mm Hg)
Filtration Opposing Forces:
Colloid Osmotic Pressure (OPg) of glomerular blood (28 - 30 mm Hg) Capsular Hydrostatic Pressure (HPc) (15 mm Hg)
NFP = 55 - (30+15) NFP = 10 mm Hg
Glomerular Filtration Rate - the amount of filtrate formed per minute by the kidneys.
There are generally three factors involved in the GFR:
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1. total surface area for filtration 2. filtration membrane permeability 3. net filtration pressure
Normal GFR for an adult is 120 - 125 ml/ min. Note a drop in glomerular pressure of 15% will stop filtration altogether.
Note also that GFR is directly proportional to the net filtration rate.
The GFR must be precisely regulated or many substances normally resorbed will be lost in the urine, OR wastes that should be expelled may be resorbed.
There are three mechanisms that help to keep the GFR relatively constant: 1. Renal Autoregulation (intrinsic controls)
2. Neural controls
3. Renin-angiotensin system
Renal Autoregulation - the kidney can maintain a relatively constant GFR regardless of
fluctuations in systemic blood pressure. This is done by regulating the diameter of the afferent and efferent arterioles. This is done in one of two ways:
vessels.
2. tubuloglomerular feedback mechanism - senses changes in the juxtaglomerular apparatus. Using the macula densa cells: these cells release a vasoconstrictor if the GFR is too high or permit vasodilation of afferent arterioles if the filtration rate is too low. This system can work in the range of 80 to 180 mm Hg. It cannot handle low systemic pressures. Below 45 mm Hg filtration stops.
Neural Control - Sympathetic control. When the sympathetic nervous system is at rest
renal vessels are maximally dilated. Sympathetic stimulation causes constriction of afferent arterioles thus decreasing filtration rate. This stimulation causes release of epinephrine from the adrenal medulla. The epinephrine in turn acts on alpha receptors on vascular smooth muscle. This indirectly starts the renin-angiotensin mechanism by stimulating macula densa cells.
The sympathetic nervous system also directly stimulates the Juxtaglomerular cells (by binding NE to beta adrenergic receptors) to release renin, which begins the renin-angiotensin mechanism.
Renin-Angiotensin mechanism - begins when juxtaglomerular cells release renin. Renin
acts on angiotensinogen (plasma protein made in the liver) to release angiotensin I which is then converted to angiotensin II by angiotensin converting enzyme.
Resorption in the kidneys is active (requires ATP) or passive depending on the substance to be resorbed.
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Sodium ions are the single most abundant cations in the filtrate. Sodium ion resorption is always active.
Obligatory water reabsorption: sodium movement establishes a strong osmotic
gradient, and water moves by osmosis into the peritubular capillaries. Here the water is “obliged” to follow the salt.
As water leaves the tubules, the relative concentration of the substances still present in the filtrate increases dramatically and, if able, they will begin to follow their
concentration gradients into the tubule cell. This is called Solvent Drag.
Some substances are not resorbed or are resorbed incompletely. This happens because: 1. they lack carriers
2. they are not lipid soluble
3. they are too large to pass through the plasma membrane pores of the tubule cells.
The most important of these substances are the nitrogenous end products of protein and nucleic acid metabolism: urea, creatinine, and uric acid. Absorptive capabilities of various regions of the renal tubules
Proximal convoluted tubule: is the most active region for reabsorption All glucose , lactate, and amino acids
65 - 70% of Na+ (linked to cotransport of other solutes or Na+-H+ exchange)
65 - 70% of water 90% of bicarbonate 50% of chloride >90% of potassium
Of the 125 ml/min of fluid filtered at the glomerulus, only about 40 ml/min remains after the PCT.
Loop of Henle
Descending limb: Water moves out freely, K+ moves back in.
Ascending limb: Na+, K+, Cl- move out, water cannot leave the ascending limb.
Distal Convoulted Tubule:
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Na+ and Cl- reabsorbed if needed by the body. This is under hormonal control. If needed almost ALL of the water and Na+ reaching this area can be reclaimed.
Na+ resorption is under the control of Aldosterone from the adrenal cortex. When
aldosterone is present almost no Na+ leaves the body via the urine. In addition the
renin-angiotensin mechanism stimulates the release of aldosterone. Aldosterone also promotes water reabsorption because water follows the Na+.
ADH also plays a role here.
Atrial Natriuretic Peptide: (ANP) is a hormone released from the atrial cardiac cells
when blood volume and/or blood pressure is elevated. ANP inhibits Na+ absorption by
closing Na+ channels. This reduces water reabsorption and therefore blood volume.
Tubular Secretion: is essentially reabsorption in reverse.
We see tubular secretion in the PCT, DCT and cortical collecting ducts, but not in the loop of Henle.
This is important for:
1. disposing of substances that are not already in the filtrate (drugs) 2. eleminating undesirable substances such as urea and uric acid 3. getting rid of excess K+
4. controlling blood pH
Osmolality: the number of solute particles dissolved in one liter of water. This is
reflected in the solutions ability to cause osmosis.
The kidneys have the important job of keeping the body fluids at a constant 300 mosm (milliosmoles). This is done by using a countercurrent exchange system.
Some common terms that apply to urinary physiology:
Acidosis: A condition in which the pH of the blood is below 7.35 Alkalosis: A condition in which the pH of the blood is higher than 7.45
Compensation: the physiological response to an acid/base imbalance that acts to normalize the pH of arterial blood.
Complete compensation: results if the arterial pH is brought to within normal limits
Partial compensation: is only partially corrected but does not fall within the normal range
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If a person has an altered blood pH due to metabolic causes, hyper/hypoventilation may bring the pH back into the normal range. This would be known as respiratory
compensation.
compensation to try to return to normal limits. Renal compensation works by changing the secretion of H+ and reabsorption of HCO3- by the kidneys.
Metabolic acidosis/alkalosis results from changes in HCO3 - concentrations in the blood.
The normal range for HCO3 - is 22 – 26 mEq/liter.
Metabolic acidosis is defined as the arterial blood HCO3 - level dropping below 22
mEq/liter. This could result from actual loss of HCO3 - as may be seen with severe
diarrhea or renal disease, or an accumulation of an acid other than HCO3 -, or failure of
the kidneys to excrete H+. If this problem is not too severe we can use respiratory
compensation (through hyperventilation) to bring the blood pH back into the normal range.
Metabolic alkalosis is defined as an arterial blood HCO3 - level above 26 mEq/liter. A loss
of acid or excessive intake of alkaline drugs can cause the blood pH to rise above 7.45. The most frequent cause is excessive vomiting which results in a substantial loss of HCl. Hypoventilation may provide respiratory compensation.
There are basically 4 steps in diagnosing acid/base imbalances: 1. determine whether the pH is high (alkalosis) or low (acidosis). 2. determine which value (PCO2 or HCO3
-) is out of range
3. If the cause is a change in PCO2 the problem is respiratory. If the cause is
HCO3
-, the problem is metabolic.
4. NOW, look at the value that doesn’t correspond with the observed pH change. If it is within its normal range there is no compensation occurring. If it is outside its normal range compensation is occurring and partially correct the problem.
The partial pressure of carbon dioxide is the single most important indicator of respiratory function.
When respiratory function is normal PCO2 ranges from 35 - 45 mm Hg.
Respiratory acidosis and alkalosis are both disorders resulting form changes in the partial pressure of CO2 (PCO2)
Values of PCO2 above 45 mm Hg indicate respiratory acidosis
Values of PCO2 below 35 mm Hg indicate respiratory alkalosis
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Respiratory acidosis is defined as an abnormally high PCO2 in arterial blood. Inadequate
exhalation of CO2 causes the blood pH to drop. Respiratory acidosis can result from slow
breathing or hampered gas exchange (pneumonia, cystic fibrosis, emphysema). Here CO2
accumulates in the blood. This causes a falling blood pH and rising PCO2. The kidneys
may provide renal compensation by increasing the excretion of H+ and the reabsorption
of HCO3 -.
The goal in treating respiratory acidosis is to increase the blow off (exhalation) of CO2.
Respiratory alkalosis is defined as an abnormally low PCO2 in the arterial blood.. The
cause of this condition is hyperventilation and CO2 is eliminated from the body faster
than it is produced.. Hyperventilation may be caused by several factors such as oxygen deficiency due to high altitude, stroke, or sever anxiety. Renal compensation may bring the blood pH into the normal range if the kidneys are able to decrease the excretion of H+
and reabsorption of HCO3 -.
Note that, unlike respiratory acidosis, respiratory alkalosis this is rarely caused by pathology,.
• h
• ttp://faculty.etsu.edu/forsman/UrinaryPhysiology.pdf •
16) Physiological changes in laparoscopy include all except a) Increased ?PCWP
b) Increased ICP c) Decreased FRC d) Increased pH D
Summary of Haemodyanamic Changes due to Mechanical pressure of C02 insufflation Increased systemic vascular resistance (SVR) Increased Mean Arterial pressure (MAP) Minimal change in heart rate (HR) Increased cerebral blood flow (CBF) Increased intracranial pressure (ICP) Decreased renal blood flow (RBF) Decreased portal blood flow Decreased splanchnic blood flow Decreased pulmonary compliance
C02 absorption Significant hypercapnia and acidosis may occur duringlaparoscopy due to C02 absorption. Hypercapnia may cause a decrease in myocardial contractility and lower arrhythmia threshold. The anticipated direct vascular effect ofhypercapnia, producing arteriolar dilation and decreased SVR,is modulated by mechanical and neurohumoral responses, including catecholamine release
http://iages.in/pdf/c_67_70.pdf
17) A 50 % increase in radius of vessel will cause rise in blood flow by a) 10 times
b) 20 times c) 5 times d) 100 times C
There are three primary factors that determine the resistance to blood flow within a single vessel: vessel diameter (or radius), vessel length, and viscosity of the blood. Of these three factors, the most important quantitatively and physiologically is vessel diameter. The reason for this is that vessel diameter changes because of contraction and relaxation of the vascular smooth muscle in the
wall of the blood vessel. Furthermore, as described below, very small changes in vessel diameter lead to large changes in resistance. Vessel length does not change significantly and blood viscosity normally stays within a small range (except when hematocrit changes).
Vessel resistance (R) is directly proportional to the length (L) of the vessel and the viscosity (η) of the blood, and inversely proportional to the radius to the fourth power (r4). Because changes in
diameter and radius are directly proportional to each other (D = 2r; therefore D∝r), diameter can be substituted for radius in the following expression.
Therefore, a vessel having twice the length of another vessel (and each having the same radius) will have twice the resistance to flow. Similarly, if the viscosity of the blood increases 2-fold, the
resistance to flow will increase 2-fold. In contrast, an increase in radius will reduce resistance. Furthermore, the change in radius alters resistance to the fourth power of the change in radius. For example, a 2-fold increase in radius decreases resistance by 16-fold! Therefore, vessel resistance is exquisitely sensitive to changes in radius.
The relationship between flow and vessel radius to the fourth power (assuming constant ΔP, L, η and laminar flow conditions) is illustrated in the figure to the right. This figure shows how very small decreases in radius dramatically reduces flow.
Vessel length does not change appreciably in vivo and, therefore, can generally be considered as a constant. Blood viscosity normally does not change very much; however, it can be significantly altered by changes in hematocrit, temperature, and by low flow states.
If the above expression for resistance is combined with the equation describing the relationship between flow, pressure and resistance (F=ΔP/R), then
This relationship (Poiseuille's equation) was first described by the 19th century French physician Poiseuille. It is a description of how flow is related to perfusion pressure, radius, length, and viscosity. The full equation contains a constant of integration and pi, which are not included in the above proportionality.
In the body, however, flow does not conform exactly to this relationship because this relationship assumes long, straight tubes (blood vessels), a Newtonian fluid (e.g., water, not blood which is
non-Newtonian), and steady, laminar flowconditions. Nevertheless, the relationship clearly shows the dominant influence of vessel radius on resistance and flow and therefore serves as an important concept to understand how physiological (e.g., vascular tone) and pathological (e.g., vascular stenosis) changes in vessel radius affect pressure and flow, and how changes in heart valve orifice size (e.g., in valvular stenosis) affect flow and pressure gradients across heart valves.
Although the above discussion is directed toward blood vessels, the factors that determine resistance across a heart valve are the same as described above except that length becomes insignificant because path of blood flow across a valve is extremely short compared to a blood vessel. Therefore, when resistance to flow is described for heart valves, the primary factors considered are radius and blood viscosity.
http://www.cvphysiology.com/Hemodynamics/H003.htm
18) The clot formed is not stable unless extensive cross linking occurs. This is done by a) Plasmin
b) Thrombin c) Factor XIII d) HMWK C
19) In a study mannitol 10g is injected iv and the concentration measured after some time is 50 mg/100ml. In this time 10% of mannitol is excreted. What is the volume of the ECF
a) 18 L b) 42 L A
Volume of ECF=amount/concentration 20) ABO blood group is an example of a) Co dominance
A
21) What is true regarding alpha and gamma neurons during voluntary movements a) Alpha acts first
b) Gamma acts first c) Both act together d) gamma 1st then aphla ANS=C
Motor neurons are divided into two groups. Alpha motor neurons innervate extrafusal fibers, the highly contracting fibers that supply the muscle with its power. Gamma motor neurons innervate intrafusal fibers, which contract only slightly. The function of intrafusal fiber contraction is not to provide force to the muscle; rather, gamma activation of the intrafusal fiber is necessary to keep the muscle spindle taut, and therefore sensitive to stretch, over a wide range of muscle lengths. This concept is illustrated in Figure 1.10. If a resting muscle is stretched, the muscle spindle becomes stretched in parallel, sending signals through the primary and secondary afferents. A subsequent contraction of the muscle, however, removes the pull on the spindle, and it becomes slack, causing the spindle afferents to cease firing. If the muscle were to be stretched again, the muscle spindle would not be able to signal this stretch. Thus, the spindle is rendered temporarily insensitive to stretch after the muscle has
contracted. Activation of gamma motor neurons prevents this temporary insensitivity by causing a weak contraction of the intrafusal fibers, in parallel with the contraction of the muscle. This contraction keeps the spindle taut at all times and maintains its sensitivity to changes in the length of the muscle. Thus, when the CNS instructs a muscle to contract, it not only sends the appropriate signals to the alpha motor neurons, it also instructs gamma motor neurons to contract the intrafusal fibers appropriately; this coordinated process is referred to as alpha-gamma coactivation. http://neuroscience.uth.tmc.edu/s3/chapter01.html
22) Which of these is secreted by beta cells of pancreas along with insulin a) Amylin
b) Glucagon like peptide A
23) Brown adipose tissue is present in all except a) Around blood vessels
b) Subcutaneous tissue c) Adrenal cortex d) Scapula
Visceral BAT includes the following: 1) Perivascular BAT around the aorta, common carotid artery, and brachiocephalic artery; in anterior mediastinum (paracardial) fat (Fig. 1); and around epicardial coronary artery and cardiac veins as well as medium-sized muscular arteries and veins including the internal mammary and the intercostal artery branches from the subclavian and aorta. The intercostal veins drain blood from the chest and abdominal walls into the azygous veins, the left joining the main right azygous vein in the latter’s thoracic cephalad course closely adjacent to the inferior vena cava before emptying into the superior vena cava (14). 2) Viscus BAT, defined as BAT surrounding a hollow muscular organ other than blood vessels, situated in variable amounts in the epicardium around the heart (Fig. 1) and in the esophago-tracheal groove, as well as greater omentum and transverse mesocolon in the peritoneal cavity. 3) BAT around solid organs, namely, kidney, adrenal, pancreas, liver, and splenic hilum including paravertebral fat, which was not examined in Heaton’s series (2) but can be seen on CT scans of the thorax adjacent to periaortic fat (Fig. 1). It lies next to the intercostal artery from which a spinal branch supplies the spinal cord (14). To our knowledge, BAT has not been described in the meninges covering the brain and spinal cord or in the subcutaneous tissue of the scalp.
http://diabetes.diabetesjournals.org/content/62/6/1783.full ---
Brown adipose tissue is sometimes mistaken for a type of gland, which it resembles more than white adipose tissue. It varies in color from dark red to tan, reflecting lipid content. Its lipid reserves are depleted when the animal is exposed to a cold
environment, and the color darkens. In contrast to white fat, brown fat is richly vascularized and has numerous unmyelinated nerves which provide sympathetic
stimulation to the adipocytes.
Brown fat is most prominent in newborn animals. In human infants it comprises up to 5% of body weight, then diminishes with age. Substantial quantities of brown adipose tissue can be detected in adult humans using positron-emission tomography,
especially when the individuals are exposed to cold temperatures.* Most of this tissue in adults is located in the lower neck and supraclavicular region. Intriguingly, there is an inverse correlation between the amount of brown adipose tissue and body mass index, with obese individuals having significantly less of the tissue than lean
individuals; this suggests that brown fat may be an important factor in maintaining a lean phenotype.
A good place to observe brown fat is in mice, where it persists into adulthood.******* Dissection of a mouse will reveal two large, lobulated masses of brown fat on the dorsal aspect of the thorax, between the scapulae.********* Masses of brown fat are also to be found around the aorta and in the hilus of the kidney.
Examination of sections of white and brown fat at low magnification reveal dramatic differences in structure, as seen below in images of mouse tissues.
http://www.vivo.colostate.edu/…/p…/misc_topics/brownfat.html
24) 7 yr old boy with presents with severe abdominal pain. On examination he has xanthomas. Blood drawn for work up has milky appearance of plasma. Which lipoprotein is increased a) Chylomicron b) Chylomicron remnants c) LDL d) HDL ANS=A http://www.rxpgonline.com/modules.php?name=usertools&file=redirect&url=http:// usmle.biochemistryformedics.com/milky-plasma-your-diagnosis/
25) If in a person, Total Cholesterol= 300mg/dL, HDL= 25mg/dL and TAG=150mg/dL, find out the value of LDL.
a) 245 b) 125 c) 95 d) 55 A Friedewald (1972) Formula: LDL = TC - HDL - TG/5.0 (mg/dL) http://homepages.slingshot.co.nz/~geoff36/LDL_mg.htm
26) In a person, LDL is highly elevated but the level of LDL receptors is normal. What could be the cause
a) Phosphorylation of LDL receptors b) ApoB100 mutation
c) Lipoprotein lipase deficiency
d) Cholesterol Acyl CoA transferased deficiency B
27) An infant at ?7months with history of vomiting and failure to thrive. Patient improved with iv glucose. After one month returns with same complaints. On evaluation found to have high glutamine and uracil. Which is the likely enzyme defect a) CPS1 b) Ornithine transcarbamoylase c) Arginase d) Arginosuccinase lyase A
The liver is the only site of the complete urea cycle. Among the six enzymes in the cycle, N-acetylglutamate synthase (NAGS), carbamyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) are
intramitochondrial whereas arginase, argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) are cytosolic.
Unlike fats and carbohydrates, protein is not stored in the body but rather exists in a balanced state of anabolism (formation) and catabolism (breakdown). Protein excess beyond normal bodily requirements comes from either excess dietary protein intake or from protein breakdown through various catabolic processes (stress of the newborn period, infection, dehydration, injury, or surgery). Amino acids liberated from excess protein are broken down, releasing nitrogen which circulates in the body as ammonia (NH3). Ammonia is then converted into urea via the urea cycle and disposed of in the urine. An enzymatic block in the urea cycle defect results in the
accumulation of excess ammonia which has toxic effects, most severe in the central nervous system causing cerebral edema.
Ammonia also circulates in the body as free ammonia or within glutamine which functions as a temporary “repository” for ammonia. Consequently, in a urea cycle defect not only does free ammonia rise
(hyperammonemia) but glutamine is also elevated. Alanine (Ala) is another amino acid that accumulates as a result of hyperammonemia due to a urea cycle defect. These two amino acid elevations (glutamine, alanine) may precede hyperammonemia and the onset of clinical symptoms and can serve as useful biochemical markers of decompensation in a patient with a urea cycle defect.
Clinical Presentation of an Acute Hyperammonemic Episode Poor feeding
Tachypnea Hypothermia Irritability Vomiting Ataxia Seizures Hepatomegaly Coma
Hyperammonemic crises in neonates or infants with OTC deficiency are frequently precipitated by sepsis. Consequently, any neonate or infant with OTC deficiency who has clinical signs of a severe illness should be evaluated for a hyperammonemic crisis precipitated by infection or any other stressor.
Clinical Assessment
Assess cardiac, respiratory, neurologic, and hydration status.
Identify potential precipitant(s) of metabolic decompensation such as infection (presence of fever) or any other physical stressor (e.g. injury, surgery).
Initial laboratory tests to order:
Plasma ammonia (1.5 ml blood in sodium-heparin tube sent STAT to lab on ice, run immediately) Plasma amino acid profile
Urine orotic acid
Liver function tests (AST,ALT, alakaline phospatase, bilirubin) Arterial or venous blood gas
Serum electrolytes, bicarbonate, BUN, creatinine Blood glucose
Blood, urine, and/or CSF cultures (as clinically indicated)
Plasma ammonia level is a direct index of CNS toxicity and is important to follow in acute management.
Plasma amino acids should be drawn at presentation and should be monitored frequently thereafter. Glutamine, as an ammonia buffer, reflects the direction of control of the hyperammonemia and, therefore, it is a useful marker for monitoring of ammonia status.
Other amino acids, including glutamate, glycine, asparagine, aspartate and lysine, may be elevated when there is an excess in waste nitrogen burden.
Please note that prolonged therapy with phenylacetate (phenylbutyrate) and/or benzoate may lead to a disproportionate decrease or only a modest elevation of glutamine and/or glycine.
Laboratory Findings in OTC Deficiency High plasma ammonia level
High plasma glutamine and alanine levels, low plasma citrulline level; low plasma arginine level Very high urine orotic acid level
Respiratory alkalosis (initially) Treatment
Immediate treatment of hyperammonemia is crucial to prevent neurologic damage and avoid associated morbidity and mortality. Cognitive outcome is inversely related to the number of days of neonatal coma in the urea cycle disorders. Rapid control of the hyperammonemia is crucial in preventing or lessening the degree of mental retardation.
Key steps of immediate treatment:
Stop all protein intake (but do not withhold protein for longer than 36-48 hours as that can promote breakdown of endogenous proteins and hamper metabolic control).
Provide intravenous fluids with dextrose and intralipids: 10%-25% IV dextrose at 1.5 times maintenance rate and intralipid at 1-3 g/kg/day to provide 120-130 kcal/kg/day. This will require a central line.
Provide ammonia scavenger medications as detailed below.
Prepare for probable hemodialysis by contacting the relevant renal and surgical specialists in anticipation of imminent need.
The treatment of a hyperammonemic crisis in a patient with a urea cycle disorder rests on the principles which are detailed in the following sections:
A. Promote waste nitrogen excretion
B. Reverse catabolism/optimize caloric intake C. Treat the underlying precipitant
A. Promote Waste Nitrogen Excretion
There are two main ways to promote ammonia detoxification: hemodialysis and medications that facilitate ammonia excretion.
Hemodialysis is the most effective way of rapidly disposing of excess ammonia and is far superior to other methods of dialysis (hemofiltration, peritoneal dialysis). Hemodialysis has the added benefit of removing amino acids such as glutamine and, in that way, disposing of additional waste nitrogen from the body. A newborn or young infant with a plasma ammonia greater than 300 μmol/L, should have hemodialysis ASAP, and administer IV Ammonul until hemodialysis is instituted. Central venous catheters should be placed in a critically ill patient in hyperammonemic crisis in anticipation of the potential for hemodialysis and the appropriate nephrology and surgical specialists should be alerted in advance for this potential need. The decision to hemodialyze is critical in preventing or minimizing irreversible CNS damage; when in doubt in the face of a markedly elevated ammonia level, the decision should be to hemodialyze as soon as possible.
Ammonia scavenger medications include IV Ammonul® (sodium benzoate and sodium phenylacetate). Sodium benzoate conjugates with glycine to form hippuric acid and sodium phenylacetate conjugates with glutamine to form phenylacetylglutamine; both compounds are excreted in the urine, thereby removing the nitrogen (N) in glycine and glutamine which contribute to the hyperammonemia.
Sodium should not be provided in supplemental IV fluids when IV Ammonul® is given since this solution contains sufficient amounts of sodium. Otherwise, hypernatremia may result.
Side effects of IV Ammonul® may occur in children, including nausea and vomiting. This may be controlled with antiemetic medications such as ondansetron, either prior to or during the infusion. Overdoses (3-5x the recommended dose) of IV Ammonul® can lead to agitation, confusion and hyperventilation. Caution should be exercised to avoid overdosing.
IV Ammonul® dosing:
0-20 kg: 2.5 mL/kg (prior to mixture with dextrose solution) IV bolus over 90 min followed by the same dose as a 24-hour infusion.
>20 kg: 55 mL/m2 (prior to mixture with dextrose solution) IV bolus over 90 min followed by the same dose as a 24-hour infusion.
IV Arginine (600 mg/kg/day) – used to provide supplemental arginine which may be deficient due to early
enzymatic blocks and to stimulate the urea cycle. After the diagnoses of citrullinemia and argininosuccinic aciduria have been ruled out, the dose may be reduced to 250 mg/kg/day.
Citrulline – used in OTC deficiency when the child is able to have enteral feeding. Citrulline (by mouth, NG or g-tube) may help pull aspartate into the urea cycle and, thus, increase nitrogen clearance.
B. Reverse Catabolism/Optimize Caloric Intake
*Diet should be planned in conjunction with a metabolic dietitian*
The caloric intake for neonates and infants with OTC deficiency in hyperammonemic crisis should be kept at least at 120-130 kcal/kg/day to reverse catabolism. Strict intake and output records should be monitored.
The caloric intake on day 1 is provided by intravenous dextrose and supplemented with intralipid to provide 120-130 kcal/kg/day. Protein intake should ideally commence within 36-48 hours to avoid breakdown of endogenous proteins but may be delayed depending on clinical status. Start protein at 0.6 grams/kg/day, administered as essential amino acids. After 48 hours of this regimen and if patient tolerates this well, the protein concentration can be increased to 1.2 grams/kg/day, half in the form of essential amino acids and the other half in the form of a natural protein source (regular infant formula or breast milk) but, avoid elemental formulas as they are high in nitrogen content. Supplemental calories are added from a non-nitrogenous formula with vitamins and minerals (Ross formula Pro-Phree® or equivalent). Thereafter, the protein intake can be gradually increased by 0.25 – 0.5 gram/kg/day increments to a maximum of 2 grams /kg/day.
Enteral feeds (oral or NG/NJ) should be started as soon as practical and that can even occur concomitant with IV nutrition and fluids if necessary.
C. Treat the Underlying Precipitant
infection or dehydration which results in a state of catabolism. Diagnostic investigation and treatment aimed at this underlying precipitant is extremely important to optimize metabolic control of the decompensation and should be undertaken at the time of initial presentation and continued throughout the management phase of
hyperammonemia.
*Caution: Do not perform a lumbar puncture (LP) before evaluating for the presence of cerebral edema, which may contraindicate an LP.
Monitoring
Plasma ammonia levels do not always directly correlate with the presence or severity of clinical signs and symptoms and, thus, monitoring of clinical status and changes in that is crucial. Clinical decisions on appropriate treatments should be based on the combination of clinical assessment and plasma ammonia levels.
Monitor ammonia levels every 4 hours, and electrolytes and arterial/venous blood gas as clinically indicated. Plasma amino acids should be monitored frequently depending on levels. If another IV is required, that solution should not contain sodium if given simultaneously with IV Ammonul®
There may be a “rebound” hyperammonemia initially as stored glutamine is metabolized to glutamate and ammonia, and with the efflux of intracellular ammonia into the ‘relatively’ ammonia-depleted blood while on treatment and, thus, it is important to continue closely monitoring plasma ammonia levels until they remain stable in the normal range. On rare occasions it may be necessary to assess the magnitude of glutamine excess in brain tissue by performing brain magnetic resonance spectroscopy (MRS).
Plasma glucose levels should be kept below 150 mg%. If hyperglycemia occurs while IV 10%-20% dextrose is supplied for added calories, an IV insulin drip at 0.01 units/kg/hour should be started to maintain plasma glucose between 100 and 150 mg%. Insulin may be increased by 0.01-0.03 units/kg/hour until desired effect is obtained. Please note that as the patient’s condition improves and anabolic homeostasis is restored, it may be necessary to rapidly eliminate or reduce the rate of the insulin infusion as hypoglycemia may develop. High IV dextrose solutions should not be decreased or stopped in the face of hyperglycemia. The goal is to keep the level from rising above 150 mg/ dl. Wide swings in glucose levels are not ideal and so plasma glucose should be kept within the above as best as possible.
Cerebral edema: Oncotic agents such as albumin will increase the overall nitrogen load but may in selected cases be considered. Mannitol has been used but may not be as effective as hypertonic saline in alleviating cerebral edema due to hyperammonemia. Steroids should never be used in a patient with hyperammonemia.
Hyperventilation is recommended, but only under close supervision.
Neurologic status should be closely monitored for signs of CNS toxicity and cerebral edema while the patient is under treatment and in the recovery period.
Caloric intake should be kept at a high level at all times to prevent catabolism. Close monitoring of the intake of calories is an essential part of treatment and monitoring of a patient with a urea cycle defect in crisis.
Avoid certain medications, such as valproic acid, as it interferes with urea cycle function and accentuates hyperammonemia.
Recovery
Once the patient is stabilized and improving, oral diet has been established, and the plasma ammonia level is stable in an acceptable range, oral scavenger medications (sodium benzoate, sodium phenylbutyrate) and oral arginine can be provided in place of their IV forms.
