47 High Yield Recall

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ANATOMY
Ø Drainage pattern to the superficial and deep inguinal lymph nodes.
- Anything from the internal genitalia (testicles, ovaries, uterus)
drains to the para-aortic lymph nodes
- But what drains into the superficial and deep inguinal lymph nodes?
- Deep inguinal lymph nodes drain the lower limb, while superficial
nodes drain the external genitalia and superficial tissues. This is why
we never resect or even biopsy via a transcrotal approach despite the
fact that the testicles drain into the para-aortics.

Ø HY TIPS
- 1. Direct hernia: leaves abdominal cavity medial to inferior
epigastric vessels
Indirect hernia: leaves abdominal cavity lateral to inferior epigastric
vessels
Femoral hernia: protrusion of abdominal viscera through femoral ring
into femoral canal
Lumbar puncture: needle into lumbar cistern between spinous processes
L3/L4 or L4/L5 Pericardiocentesis: wide bore needle inserted through
5th or 6th intercostal space near sternum. Careful not to puncture
internal thoracic artery
- 2. Thyroid C5 Duodenum T12-L1
Sternal notch T2 Kidneys T12-L3
Bifurcation of trachea T4-T5 Conus medularis L1-L2 adult, L3 newborn
Heart: Base T6-T9 Umbilicus L4
Apex 5th left intercostal space
- 3. Knee: 1. Patellar ligament- damage to femoral nerve or spinal cord
L2-L4. Loss of patellar reflex 2. MCL- tear also tears medial meniscus.
Passive abduction of extended leg at knee joint. 3. LCL- passive
adduction of extended leg at knee joint. 4. ACL- anterior drawer sign.
5. PCL- posterior drawer sign. 6. Terrible triad- MCL, medial meniscus
and ACL tears.
- Hip: 1. Posterior dislocation- head of femur moves posterior to the
iliofemoral ligament. Presents with lower limb that is flexed at hip
joint, adducted, medial rotated and shorter than opposite limb. 2.
Fracture of neck of femur presents laterally rotated and shortened.
- Shoulder: 1. Dislocation- may be anterior or posterior. If anterior
then axillary nerve may be damaged. 2. Separation- results in a
downward displacement of clavicle.
- Clavicle: 1. Fracture- most common at medial 1/3. Results in upward
displacement of proximal fraagment and downward displacement of distal
fragment
- 4. Brachial Plexus: 1. Axillary n- dislocation of shoulder, abduction
(deltoid) and lateral rotation (teres minor) are compromised. 2. Long
thoracic n- winging of scapula (serratus anterior). 3. Radial n- wrist
drop (extensors of forearm). 4. Median n- ape hand (thumb muscles) and
flexors of forearm if damage is at elbow or above. 5. Ulnar n- claw
hand and radial deviation of hand, loss of some flexors if at elbow or
above.
- 5. Peripheral nerves: 1. Common peroneal n- foot drop (tibialis
anterior m) and inversion (peroneus muscles). 2. Deep peroneal n.
entrapment- Compression of anterior compartment muscles of the lower
leg by ski boot or athletic shoes that are too tight. Causes pain in
the dorsum of the foot that radiates to the space between the first two
toes.

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- 6. Hands: 1. Carpel Tunnel Syndrome- compression of median nerve by
inflammation, weakened flexion, abduction and opposition of thumb, loss
of extension of index and middle fingers, sensory loss of index, middle
and half of ring fingers and palmar part of thumb.
2. Cubital tunnel syndrome- sorry I was not able to find this one.
3. Dupuytren’s contracture- progressive fibrosis of palmar aponeurosis,
pulls digits into marked flexion at MCP joints.
- 7. Blood-testes barrier: There is a barrier that exists between the
blood vessels that supply the testes (branches of the testicular artery
and vein) and the duct system in which spermatozoa are produced and
transported. The testis is derived partly from celomic mesoderm and
partly from intermediate mesoderm with the blood vessels migrating in
around the duct system.
- 8. Abdominal arteries: 1. Celiac trunk(CT)-FOREGUT-left gastric a.,
splenic a., hepatic a. 2. Superior messenteric a.(SMA)- MIDGUT- part of
duodenum through proximal 2/3 of transverse colon. 3. Inferior
mesenteric a.(IMA)-HINDGUT- distal 1/3 of transverse colon to upper
rectum
- Collaterals: 1. Internal thoracic a. to superior epigastric a. to
inferior epigastric a. 2. Superior pancreaticoduodenal a.(from CT) to
inferior pancreaticoduodenal a. (from SMA) 3. Middle colic a. (from
SMA) to left colic artery (from IMA) 4. Marginal a. (from SMA and IMA)
5. Superior rectal a. (from IMA) to middle rectal a. (from internal
iliac a.)
- 9. Bone: 1. Metaphysis: between epiphysis and diaphysis. 2.
Epiphysis: growth plate responsible for linear bone growth. 3.
Diaphysis: long part of bone responsible for annular bone growth.

NEUROANATOMY
Ø INJURIES TO THE BRACHIAL PLEXUS: A REVIEW:
[ Follow Ups ] [ Post Followup ] [ Step 1 ]
Posted by Keri from IP 64.252.67.133 on March 06, 2003 at 05:46:40:
Hi.. here are some useful notes... If anyone has more on this topic,
please add.
INJURIES TO THE BRACHIAL PLEXUS:
1. Waiter's Tip
The waiter's tip injury occurs with damage to the superior trunk of the
brachial plexus (C5-C6). The superior trunk can be damaged by stab
wounds or when the head and trunk is separated from the shoulder during
falls. The major nerves that would be damaged by this injury are the
suprascapular, musculocutaneous, and axillary nerves. The major muscle
affected by disruption of these nerves are the deltoid (abductor of the
shoulder), supraspinatus (abductor of the shoulder), infraspinatus
(lateral rotator of the shoulder), teres minor (lateral rotator of
shoulder), biceps brachii (supinator and flexor of forearm), and
brachialis (flexor of elbow). Injury to these muscles results in a
position called the waiter's tip. As shown in the diagram below the
limb hangs limply by the side, is medially rotated, with the forearm
pronated due to loss of the supinating action of the biceps brachii.
§ Big Snell, pg 480
2. Claw Hand
Claw Hand results from an injury to the inferior trunk of the brachial
plexus (C8-T1). This injury results from excessive abduction of the arm
such as when a person grasps onto something to prevent falling. The

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nerve fibers from this trunk run in the median and ulnar nerve and
supply all the small muscles of the hand (lumbricals and interossei).
Paralysis of these intrinsic muscles of the hand causes the fingers to
assume the "claw hand" position demonstrated below. This position is
caused by the unopposed action of the extensor digitorum (which extends
the metacarpophalangeal joints) and the flexor digitorum superficialis
and profundus (which flex the fingers). Normally, these muscles are
opposed by the lumbricals and the interosseus muscles.
§ Lecture Notes
3. Wrist Drop
Wrist drop is caused by injury to the posterior cord and the radial
nerve in the axilla. This injury can be caused by ill-fitting crutches
or a downward dislocation of the humerus. Disruption of the radial
nerve results in paralysis of the triceps, anconeus, and extensor
muscles of the wrist. The person will be unable to extend the elbow,
wrist, or digits. The resulting position of the upper limb,
demonstrated in the diagram below, is called wrist drop.
§ Big Snell, pg 484
4. Median Nerve Palsy
Injury to the median nerve within the elbow region results in some
characteristic deficiencies (which you should be able to predict by
understanding the distribution of the nerve). The arm muscles are not
affected because none of them are supplied by the median. However,
pronation of the forearm, flexion of the wrist and digits, and movement
of the thumb are severely affected. The pronator muscles of the forearm
and the long flexors of the wrist and fingers will be paralyzed, except
for the flexor carpi ulnaris and medial half of the flexor digitorum
profundus. When the patient tries to make a fist, as shown below, the
index and to a lesser extent middle fingers remain straight, while the
ring and little finger flex.
§ Big Snell, pg 486
5. Axillary nerve injury
The axillary nerve may be injured by fracture of the humerus or
dislocation of the shoulder. Following severance of the axillary nerve,
the deltoid muscle is paralyzed and atrophies.
6. Ulnar nerve palsy
The ulnar nerve can be damaged when the medial epicondyle of the
humerus is damaged (like when you hit your funny bone). Ulnar nerve
damage leads to paralysis of the flexor carpi ulnaris, medial half of
the flexor digitorum profundus, and all of the small muscles of the
hand except for the thenar muscles and the first two lumbricals. With
paralysis of these muscles, a person is unable to flex the ring or
little finger, adduct or abduct the digits, or adduct the thumb. The
hand assumes the characteristic position shown below. The
metacarpophalangeal joints become hyperextended due to paralysis of the
lumbricals and interosseus muscles, which usually flex these joints.
The interphalangeal joints are flexed- also due to paralysis of the
lumbrical and interosseus muscles , which usually extend the joints.
This condition is most marked in the medial two digits. In addition,
there will be wasting of the hypothenar eminence and hollowing between
the metacarpal bones due to atrophy of the hypothenar and interossei
muscles.
§ Big Snell, pg 488

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6. Winged Scapula
Winged scapula results from injury to the long thoracic nerve, a
supraclavicular branch (C5-C7) of the brachial plexus. This nerve to
the serratus anterior lies on the medial wall of the axilla. The nerve
may be injured by a stab wound, weight lifting, or a mastectomy. The
paralyzed serratus anterior can no longer keep the scapula against the
chest wall, which leads to the winged position shown below.
§ Big Snell, pg 481
KNOW THESE!! and also know how they would look like!!!
ADDENDUM:
Erb palsy may result in phrenic nerve damage(C3-5).
Klumpke's palsy can cause Horner's syndrome, becuase the sympathetic
innervation of the face arises from the T1 root.
Know the dysfunction, too!
Dysfunction of the long thoracic nerve leads to paralysis of the
serratus anterior muscle. Affected patients may not complain of pain,
but there is impairment in the last 30 degrees of overhead arm
extension. The scapular rhythm also is disrupted, and the scapula may
draw away from the thoracic cage; this is often referred to as winging
of the scapula [2]. To demonstrate winging, the patient presses the
outstretched arms against a wall; the involved scapula projects from
the thorax as viewed from behind the patient (UpToDate)
Ø > "Romberg sign"?
- 1. ask patient to stand with feet together and CLOSE eyes- if sway-->POSITIVE ROMBERG! LESION IN DORSAL COLUMNS
- 2. If patient sways with eyes OPEN ---> CEREBELLAR DAMAGE..
- Is it because when you close your eyes, you are totally relying on
proprioceptive info going through the cerebellum where as with the eyes
open, you are using visual clues to maintain balance
Ø 1. Nerve involed when ptosis + dilated pupil? Also
2 . how will the eye look in Horners syndrome?
- CN III palsy can cause ptosis, down and out eye deviation, and
sometimes a dilated pupil and reduced accommodation.
- Horner syndrome involves the triad of ptosis, miosis, and anhidrosis
(lack of sweating due to a lesion of the cervical sympathetic nerve).
- Ptosis with dilated pupil is due to CN 3. it innervates lavater pal
sup, also CN 3 innervates, sphincter pupillea (NEAR RESPONSE)and
ciliary
- Also, Lesion of OPTIC NERVE:
-If you place light in the normal eye--->Both eyes constrict.
-If you place light in the affected eye --->Affected eye dilates.
- Lesion of OCULOMOTOR NERVE:
-If you place light in either eye--->Normal eye constrices and affected
eye does not.

Ø Re: Pseudobulbar palsy
- Pseudobulbar palsy results from the degeneration of corticobulbar
pathways to V, VII, X, XI and XII cranial nerve nuclei with sparing of
the III, IV and VI nerve nuclei.
- Pseudobulbar palsy is a set of clinical signs on examination, not a
diagnosis. The features include slowed slurred speech, difficulty with
swallowing, weakness of face, tongue, and swallowing muscles, a

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tendency for uncontrollable laughter or crying, and brisk jaw and gag
reflexes.
- The most common causes of pseudobulbar palsy are multiple bilateral
strokes, multiple sclerosis, amyotrophic lateral sclerosis, progressive
supranuclear palsy, some forms of static and progressive childhood
diseases.
Ø IMAGING TIPS (HY):
TO BE CONFIDENT IN NEURORADIOLOGY , JUST GO TO YOUR MED SCHOOL/HOSPITAL
LIBRARY AND PICK UP ANY 3 BOOKS IN RADIOLOGY WHICH HAVE CT SCANS/MRI.
AT AN INTERN LEVEL THEY DO NOT EXPECT YOU TO DIAGNOSE RARE CONDITIONS ,
YOU SHOULD KNOW THE COMMON CT/MRI
1)CT HEAD-- HAEMORRAGE --SEEN AS WHITE OPACITY
2)SUBDURAL --SEEN AS CONVEX OPACITY CAN BE OF SAME ATTENUATION ASTHAT
OF BRAIN BUT SHOULD BE IDENTIFIABLE
3)EXTRADURAL--- CONVEX OPACITY
4)MENINGIOMA-- DURA BASED BROAD MASS SMOOTH CONTOUR
5)GLIOBLASTOMA--- IRREGULAR MASS WITH ENTENSIVE SURROUNDING EDEMA
6)RING ENHANCING LESIONS--TUMORS/ ABSCESS/IN AIDS PATIENT IT IS
TOXOPLASMOSIS
7)SUBARCHNOID---GOOD HISTORY PLUS BLOOD IN CISTERN
THAT IS PROBABLY THE LIST FOR CT HEAD. MOST LIKELY ASKED.
MRI
1) CORONAL VIEW-- PITUITARY TUMOR
2)ARNOLD CHIARI SYNDROME
3)SYRINGOBULBIA/MYELIA---DILATED CENTRAL CANAL
4)SPINAL CORD COMPRESSION
THESE ARE THE MOST COMMON ONES
START LOOKING UP IN THE FIRST BOOK FOR THESE SCANS AND UNDERSTAND THEM.
NOW LOOK INTO THE SECOND BOOK AND TRY TO DIAGNOSE THEM
SEE WHAT MISTAKES YOU MADE AND THEN GO THRU THE THIRD BOOK AND GIVE THE
DIAGNOSE . I CAN ALMOST BET THAT YOU WILL SCOREMOST OF THEM CORRECTLY.
ASHDOC
TO BE CONFIDENT IN NEURORADIOLOGY , JUST GO TO YOUR MED SCHOOL/HOSPITAL
LIBRARY AND PICK UP ANY 3 BOOKS IN RADIOLOGY WHICH HAVE CT SCANS/MRI.
AT AN INTERN LEVEL THEY DO NOT EXPECT YOU TO DIAGNOSE RARE CONDITIONS ,
YOU SHOULD KNOW THE COMMON CT/MRI
1)CT HEAD-- HAEMORRAGE --SEEN AS WHITE OPACITY
2)SUBDURAL --SEEN AS CONVEX OPACITY CAN BE OF SAME ATTENUATION ASTHAT
OF BRAIN BUT SHOULD BE IDENTIFIABLE
3)EXTRADURAL--- CONVEX OPACITY
4)MENINGIOMA-- DURA BASED BROAD MASS SMOOTH CONTOUR
5)GLIOBLASTOMA--- IRREGULAR MASS WITH ENTENSIVE SURROUNDING EDEMA
6)RING ENHANCING LESIONS--TUMORS/ ABSCESS/IN AIDS PATIENT IT IS
TOXOPLASMOSIS
7)SUBARCHNOID---GOOD HISTORY PLUS BLOOD IN CISTERN
THAT IS PROBABLY THE LIST FOR CT HEAD. MOST LIKELY ASKED.
MRI
1) CORONAL VIEW-- PITUITARY TUMOR
2)ARNOLD CHIARI SYNDROME
3)SYRINGOBULBIA/MYELIA---DILATED CENTRAL CANAL
4)SPINAL CORD COMPRESSION
THESE ARE THE MOST COMMON ONES
START LOOKING UP IN THE FIRST BOOK FOR THESE SCANS AND UNDERSTAND THEM.
NOW LOOK INTO THE SECOND BOOK AND TRY TO DIAGNOSE THEM
SEE WHAT MISTAKES YOU MADE AND THEN GO THRU THE THIRD BOOK AND GIVE THE
DIAGNOSE . I CAN ALMOST BET THAT YOU WILL SCOREMOST OF THEM CORRECTLY.

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ASHDOC

Ø Re: Watershed Areas
- Brain
- GIT – Splenic flexure and Rectosigmoid
- watershed areas are areas where there may be the first sign of any
vascular insult.in the brain the region supplied by the ACA and the MCA
and likewise in the GIT the area of the colon supplied by the SMA and
the IMA......
- By disulfiramlike:
- Watershed areas are those regions of the cerebral cortex that are at
junctions of major arterial supplies. For example, consider the
anterior cerebral artery and middle cerebral artery. The anterior
cerebral artery supplies the region of the primary motor cortex (i.e.
precentral gyrus)with cell bodies of upper motor neurons destined to
eventually synapse with lower motor neurons that serve the lower
extremities. The middle cerebral artery supplies the region of the
primary motor cortex (i.e. precentral gyrus) with cell bodies of upper
motor neurons destined to eventually synpase with lower motor neurons
that serve the face and upper extremities. BUT - the region of the
precentral gyrus containing the cell bodies of upper motor neurons that
will synapse with lower motor neurons destined for the upper
extremtieis lies BETWEEN THE TERRITORY OF DISTRIBUTION OF THE ANTERIOR
AND MIDDLE CEREBRAL ARTERIES (i.e. between the medial part of the
precentral gyrus and lateral part of the precentral gyrus). IT IS A
WATERSHED AREA. BECAUSE IT IS POSITIONED FURTHEST AWAY FROM AN ARTERIAL
SUPPLY, it is particularly susceptible to ischemia. A WATERSHED INFARCT
produces an infarction in a watershed area. A WATERSHED INFARCT may
arise from global cerebral ischemia secondary to hypoperfusion of the
cerebral cortex (e.g. from heart failure). BECAUSE THE WATERSHED AREAS
ARE FURTHEST FROM ARTERIAL SUPPLIES, THEY ARE PARTICULARLY SUSCEPTIBLE
TO UNDERGO INFARCTION. The other clinically significant watershed area
is the region of the cortex that lies in between the territories of
distribution of the middle cerebral and posterior cerebral arteries.
But, from my reading, the watershed area lying at the junction of the
territories of distribution of the middle cerebral and anterior
cerebral arteries is of most clinical significance. SUCH A WATERSHED
INFARCT WOULD PRODUCE HAND WEAKNESS.
Ø Spinal Cord Lesions:
Amyotrophic lateral sclerosis:combination of UMN & LMN symptoms
(pyramidal/anterior horn cells)
Tabes dorsalis: bilateral posterior columns
B12 def: post column & corticospinal
Polio: anterior horn cells
Guillian-barre: peripheral nerve invlt: motor and sensory
Syringomyelia: anterior white commissure:bil pain and temp loss in tht
area only
ASA occlusion : all areas except the post cloumns
PSA occlusion : ipsilateral post column
Ø NERVE INJURIES:
LOWER LIMB:hey the folln are effects of injuries to the various
nerves(excluding any overlaps)
1)Superior gluteal nerve :
supplies gluteus medius and minimus

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weakness in abduction of thigh ,inability to stabilize pelvis
(trendelenberg's gait)
2)Inferior gluteal nerve :
supplies Gluteus maximus
weakness in extension of thigh
difficulty getting up from sitting position
3)Femoral nerve
supplies anterior thigh muscles
weakness or loss of flexion of hip & extension of knee(ANASTHESIA OVER
ANTERIOR THIGH)
4)Obturator nerve
supplies medial thigh muscles
weakness or loss of adduction of thigh(ANASTHESIA OVER MEDIAL THIGH)
5)Sciatic nerve
supplies posterior thigh muscles
loss of function below knee
weakness or loss of extension of thigh & flexion of knees(ANASHTESIA
OVER POSTERIOR THIGH)
6).Tibial nerve
supplies posterior leg muscles
loss of inversion of foot,loss of plantar flexion of foot and flexion
of toes (ALSO REMEMBER ANASTHESIA OF PLANTAR ASP
OF FOOT& POSTERIOR LEG)
7)Common peroneal nerve
supplies muscles of anterolateral leg region
Loss of dorsiflexion of foot(foot drop)
loss of extension of toes and loss of eversion of foot(ANASTHESIA OVER
DORSAL ASP OF FOOT & ANTEROLAT LEG)
Ø Epidural hematomas are the result (in almost all circumstances) of
skull fractures, with sharp edges of bone cutting into the dural
arteries (mostly the middle meningeal artery) which lie on the outer
(periosteal) surface of the dura.
Ø We have to know this... they could give a question with obstruction
and ask where the accumulation results... anyway, here is the flow of
CSF-- a mnemonic: CSF LIVES IN THE CNS, FLOODING FORWARD (LIKE ME),
SPLASHING/SWIMMING, AROUND.
CSF = CHOROID PLEXUS (site of production)
LIVES = LATERAL VENTRICLE
IN = INTERVENTRICULAR FORAMEN OF MONROE
THE = THIRD VENTRICLE
CNS = CEREBRAL AQUEDUCT
FLOODING = FOURTH VENTRICLE
FORWARD(LIKE ME) = FORAMEN OF LUSHKA AND MAGENDIE
SPLASHING/SWIMMING = SUBARACHNOID SPACE
AROUND = ARACHNOID GRANULATIONS (site of resorption)
Ø EYE SIGNS:
I found this useful table from CLINICAL NEUROANATOMY, by Waxman.
YOKE MUSCLE COMBINATIONS
CARDINAL DIRECTION OF GAZE-------------------MUSCLE
--EYE UP,RIGHT---RT SUP RECTUS & LEFT INF OBLIQUE
--EYES RT--RT LATERAL RECTUS,LEFT MEDIAL RECTUS.
--EYES DOWN, RT---RT INF RECTUS & LT SUP OBLIQUE.
--EYES DOWN, LEFT--RT SUP OBLIQUE & LEFT INF RECTUS.
--EYES LEFT-----RT MEDIAL RECTUS & LEFT LATERAL RECTUS.
-EYES UP,LEFT--RT INF OBLIQUE & LEFT SUP RECTUS

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--------------------------------------------------PARALYSIS OF INDIVIDUAL MUSCLE
MUSCLE------NERVE---DEVIATION OF---DIPLOPIA---DIECTION
OF IMAGE
EYE BALL PRESENT
WHEN LOOKING
1.MED RECTUS-3---OUTWARD(EXT SQUINT)--TOWARD NOSE-direction of image vertical.
2.sup rectus-3-downward/inward--upward/outwarddirection of image-oblique.
3.inf rectus-3-upward/inward--downward/outward-direction of imageoblique.
4.inf oblique- 3-downward/outward--upward/inward-direction of image-oblique.
5.sup oblique-4-upward/outward--downward/inward-direction of image-oblique.
6.lateral rectus--6--inward(interal squint)--toward temple.
direction of image- vertical
Ø what is extra axial brain hemorrhage and intra axial brain
hemorrhage?
- Ans. Extra-axial bleeding which is usually subdural or epidural
bleeding. This is blood that is on the surface of the brain and not in
the substance of the brain. This has a characteristic appearance as
bright color on the surface of the brain. A subdural blood clot would
be biconcave or crescentic in appearance. An epidural blood clot is
characteristically biconvex or lenticular in appearance.
- Intraaxial bleeding is a hemorrhage in the substance of the brain and
it has no characteristic appearance except that it is in the brain
matter and not on the surface of the brain.
Ø Visual Field Defects
- The probable location of lesions producing visual defects is a
favorite USMLE topic (and is also well worth knowing if you have
occasion to work up such a patient). Here is a list that may help you
sort through these problems:
Central scotoma ~ macula
Ipsilateral blindness ~ optic nerve
Bitemporal hemianopia ~ optic chiasm
Homonymous hemianopia ~ optic tract
Upper homonymous quadrantanopia ~ temporal optic radiations
Lower homonymous quadrantanopia ~ parietal optic radiations
Also, cortical lesions produce defects similar to those of the optic
radiations, but may spare the macula.
Ø Amyotrophic lateral sclerosis: combination of UMN & LMN symptoms
(pyramidal/anterior hoen cells)
Tabes dorsalis: bil posterior columns
B12 def: post column & corticospinal
Polio: anterior horn cells
Guillian-barre: peripheral nerve invlt: motor and sensory
Syringomyelia: anterior white commissure: bilateral pain and temp loss
in the area only
Ø ASA occlusion: all areas except the post cloumns
PSA occlusion: ipsilateral post column

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NERVE INJURIIES:
LOWER LIMB: the follng are effects of injuries to the various
nerves(excluding any overlaps)
1)Superior gluteal nerve:
supplies gluteus medius and minimus
weakness in abduction of thigh ,inability to stabilize pelvis
(trendelenberg's gait)
2)Inferior gluteal nerve:
supplies Gluteus maximus
weakness in extension of thigh
difficulty getting up from sitting position
3) Femoral nerve
supplies anterior thigh muscles
weakness or loss of flexion of hip & extension of knee (ANESTHESIA OVER
ANTERIOR THIGH)
4) Obturator nerve
supplies medial thigh muscles
weakness or loss of adduction of thigh (ANESTHESIA OVER MEDIAL THIGH)
5) Sciatic nerve
supplies posterior thigh muscles
loss of function below knee
weakness or loss of extension of thigh & flexion of knees(ANESHTESIA
OVER POSTERIOR THIGH)
6) Tibial nerve
supplies posterior leg muscles
loss of inversion of foot,loss of plantar flexion of foot and flexion
of toes (ALSO REMEMBER ANESTHESIA OF PLANTAR ASP OF FOOT& POSTERIOR
LEG)
7) Common peroneal nerve
supplies muscles of anterolateral leg region
Loss of dorsiflexion of foot(foot drop)
loss of extension of toes and loss of eversion of foot( ANESTHESIA OVER
DORSAL ASP OF FOOT & ANTEROLAT LEG)
Ø APHASIAS
1]Aphasia--- unable to repeat sentence
Type -- Speech- Comprehension -Localization
a] Expressive (Broca) -- Nonfluent- good - Lower posterior frontal
b] Receptive (Wernicke)-- Fluent -poor- Posterior superior temporal
c] Conduction-- Fluent -good- Usually parietal operculum
d] Global -- Nonfluent- poor -Large perisylvian lesion
2]Aphasia, able to repeat sentence well
Type- Speech -Comprehension -Localization
a]Tanscortical motor -- Nonfluent- good- Anterior to Broca's area or
supplementary speech area
b]Transcortical sensory -- Fluent -poor- Surrounding Wernicke's area
posteriorly c]transcortical mixed -- Nonfluent- poor- both of the above
d]Anomic-- Fluent- good -Angular gyrus or second temporal gyrus
The term applies to those whose major symptom is word retrieval
difficulties in spontaneous speech and naming tasks. The spontaneous
speech of anomic aphasics is fluent and grammatically correct, but is
marked by word retrieval failures. The word retrieval failures generate
unusual pauses, circumlocution ("talking around" missing words) and
substitution of nonspecific words such as "thing" for missing words.

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Ø A 55-year-old man complains of numbness in both legs and progressive
inability to walk over the past 2 months. Physical examination is
normal except for a decreased perception of light touch and pain in the
lower extremities as well as bilateral leg weakness. There is no
sensory level. Laboratory workup is remarkable for a hematocrit of 30
percent and elevated total protein. Serum protein electrophoresis
reveals an M spike. The etiology of this patient's weakness is most
likely
A necrosis of central nervous system gray and white matter
B inflammation of dorsal root ganglia
C loss of cerebellar Purkinje cells
D elaboration of tumor-associated protein that elicits an immune
response that is cross-reactive with peripheral nerves
E tumor-elaborated immunoglobulin that is reacting with myelin
components
Ans. looks like peripheral neurophaty, in this case could be as a
result of primary amyloidosis (ligth chain) so i go for...
E- tumor-elaborated immunoglobulin that is reacting with myelin
components
Ø Patient has meningioma located in the parasaggital region of the falx
cerebri, what neurological deficit might this produce?...Ans. leg
weakness or paralysis
Ø A 10 year old girl exhibits neurological signs, performance in school
degenerates. several months later she develops a seizure, ataxia, and
focal neurological symptoms. She is eventually quadraparetic, spasctic
and unresponsive. She dies in one year. What viral disease did this
child have at one year of age?.. and what is this disorder
called?...ans. measles SSPE
Ø Where do myxopapillary ependymomas frequently occur?
medulla
pons
cerebellum
conus medullaris
cerebral ventricles ans. Conus Medullaris
Actually Filum terminale
Ø Lesions of which nerves will produce imposibillity of heel/toe
walking? Ans. impossible heal with common peroneal & Tibial N 4 the
toe..
Ø BRS says that in lesions of spinal cord:
-lesion of lateral corticospinal tract---> ipsilateral motor deficit
-lesion of ventral corticosp tract---> contralateral deficit
This is true only when the lesion is under pyramidal decussation in
first case and above spinal decusation in second case right? At what
level is decussation of ventral tract? Thanks. Ans. A lesion of the
lateral corticospinal tract in the spinal cord below the decussation
always results in an ipsilateral spastic weakness below the lesion. The
ventral corticospinal tract crosses at the level of the cervical cord
where its axons innervate lower motor neurons to neck muscles. An
isolated lesion of this tract in the neck (rare) may result in a

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spastic weakness of cervical muscles, but since this tract is not well
understood, and rarely lesioned in isolation, it is not a prominent
test feature on the USMLE.
Ø Name the site of lesion in the folln:(i would suggest u guys to draw
a cut section of brain stem or spinal cord and then go abt these
questions even though u will be able to guess the lesions right
away..will be good for the exam..)
- 1) Pt experiances decresred proprioception in left upper extremity
,decreased pain-temp sensation on right side of body below neck
,decreased pain -temp on left half of face..
- 2) Cerebellar dysfunction with right sided ataxia, loss of pain-temp
over right face and left body,hoarseness, diff swallowing,loss of taste
on right, vertigo &nystagmus
- 3) Left hemipalegia with inabilty of right eye to abduct
- 4) Paralysis of right lower facial muscles and right upper extremity
and inability to adduct left eye, left ptosis & dilatation of left
pupil, tongue deviates to right
- 5) Left sided headache,total paralysis of left side of face with
vertigo and left sided hearing loss
- 6) Nystagmus, bilateral internuclear ophthalmoplegia, central scotoma
of right eye, weakness of right lower extremity with postive babinski,
urinary incontinence, right ptosis and difficulty in adducting right
eye
- 7) Pt has no pupillary reaction at all to light shined on left
side.there is reaction to light in both eyes when light is shined on
right side
- 8) Pupillary reaction to light only on right side..whether light is
shined on left or right eye
- 9) Patient has inability to move right eye past midline on attempted
left conjugate deviation but convergence is preserved.
- 10) Neither eye blinks on touching right cornea but both eyes blink
on touching left cornea
- 11 )Only left eye blinks on touching either right or left cornea
- 12) Tremor of right arms and legs due to a red nucleus lesion.. Which
red nucleus is affected right or left?
Ans.
1)left lower medulla
2) right upper medulla
3) right pons
4 left mid-brain
5) left sided ponto cerebellar tumor
6) multiple sclerosis
7) left CN 2
8) left CN 3
9) right medial longitudinal fasiculus
10) right CN 5
11) right CN 7
12) left red nucleus
Ø A 35 year old female is brought to the emergency department by her
husband who says that she complained of severe headaches and then lost
consciousness. She is unable to mover her arms and legs, but can blink
her eyes. In which of the following structures is this womans lesion
located?
cervical spinal cord

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medulla oblongata
midbrain
pons
thalamus
I was wondering about the question. The answer can be Pons (bilateral
medial inferior pontine syndrome) but there will be loss of tactile
sensation from the trunk & extremities (Dorsal Coloumn medial lamniscus
pathway)&CN 6
2nd answer can be medulla - medial medullary syndrome caused by the
basilar artery but there will ba again Dorsal coloumn medial lamniscus
pathway damage & CN 12
According to myself this one can be the Kernohan notch caused by the
increase in the intracerebral pressure causes the damage to the
corticospinal & corticobulbar fibers against the tentorium cerebelli
Please write the explanation if you have
Thanks
Ans. the patient sustained a hemorrhage that has destroyed her ventral
pons, descending corticospinal and corticobulbar fibers are
interrupted. The patient is unable to move the facial, pharyngeal and
limb musculature, leaving her paralyzed and unable to speak. This is
locked in syndrome, patient is aware of being locked within her body.
Only vertical eye movements and elevation of the eyelids are possible,
so patient is blinking or moving their eyes. Lesions of the medulla
typically involve the medial or lateral aspect. lesions of the lateral
medulla is known as the posterior inferior cerebellar artery syndrome,
or wallenberg syndrome
Ø Medial inferior pontine syndrome:
occlusion of the paramedian branches of the basilar artery
Symptoms: 1)Loss of the contralateral spastic hemiparesis
(Corticospinal tract)
2)Medial Lamniscus Lesion results contralateral loss of tactile
sensation from the trunk & extremities
3) Cn6 damage results ipsilateral lateral rectus muscle paralysis (The
imporant & easy differentiation)
Ø Carotid artery occlusion : there are 2 carotid arteries external &
internal. I do not know which one r u talking about or about common
carotid artery.
Ø Pontine lesions : there are 3 lesions
1) Medial inferior pontine syndrome Lateral rectus muscle damage medial
strabism inabilty to abduct the eye
2) AICA : Horner's syndrome
3) MLF : here eye will deviate to the side of lesion CN3 palsy causes
medial rectus muscle damage results in the inability to adduct the eye.
Ø On CSF: CSF from the lumbar region contains 15-45 mg/dl protein and
50-80 mg/dl glucose. Protein concentration in cisternal and ventricular
CSF is lower. Normal CSF contains 0-5 mononuclear cells. The CSF
pressure, measured at lumbar puncture (LP), is 100-150 mm of H2O with
the patient lying on the side and 200-300 mm with the patient sitting
up.
Ø CSF Blood Barrier: It's tight junctions between epandimal cells.(but
in blood brain barrier,astrocytes+tight junctions of endothelial
cells).

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Ø On Bacterial Meningitis:
Table 2.Typical CSF findings in patients with bacterial verses
nonbacterial (aseptic) meningitis
CSF characteristic-- Bacterial
meningitis------------------------------------------------------------------------------Opening pressure----- Elevated (>180 mm H2O
------------------------------------------------------------------------------White blood cell count-- Increased (often >1,000/mm3),
neutroplipredominance
------------------------------------------------------------------------------Glucose level Decreased (<40 mg/dL)
------------------------------------------------------------------------------CSF-serum glucose ratio <0.3
------------------------------------------------------------------------------Protein level Increased (often >100 mg/dL)
------------------------------------------------------------------------------Gram stain results Stainable organisms present in 50%-80% of untreated
cases
------------------------------------------------------------------------------Bacterial culture results Positive
------------------------------------------------------------------------------CSF, cerebrospinal fluid.
> On Aseptic Meningitis:
CSF characteristic Nonbacterial meningitis
------------------------------------------------------------------------------Opening pressure Normal or slightly elevated
------------------------------------------------------------------------------White blood cell count Increased (10-2,000/mm3), lymphocyte
predominance

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------------------------------------------------------------------------------Glucose leve; Normal (>45 mg/dL)
------------------------------------------------------------------------------CSF-serum glucose ratio >0.6
------------------------------------------------------------------------------Protein level Normal or increased
------------------------------------------------------------------------------Gram stain resultsNo stainable organisms
Bacterial culture results Negative
Ø Causes of Aseptic Meningitis:
Viral infection, SLE, Drugs (Ibuprofen?)
Ø ON FRONTAL LOBE TUMORS: tumors affecting the frontal convexity, often
produce
1] progressive hemiparesis,
2]focal or generalized seizures, and
3]mental changes.
CONVULSIVE seizures may precede other symptoms by months or years.
APHASIA may accompany a tumor of the DOMINANT hemisphere.
A tumor at the BASE of the frontal lobes (particularly meningioma of
the olfactory groove) can produce IPSILATERAL ANOSMIA;
aAtumor on the MEDIAL surface can cause URINARY URGENCY or
incontinence. MENTAL CHANGES, especially inattention and apathy, and
ataxic gait are common when the tumor spreads across the CORPUS
CALLOSUM to both frontal lobes
Ø ON PARIETAL LOBE TUMORS:
- May produce generalized or SENSORY focal seizures. Cutaneous tactile,
pain, and temperature senses are UNIMPAIRED,
but STEREOGNOSIS and CORTICAL SENSORY modalities (eg, position sense,
two-point discrimination) are IMPAIRED contralaterally.
- Contralateral homonymous hemianopia, apraxia, and anosognosia (no
recognition of bodily defects) may also be present.
- DENIAL of illness is characteristic.
- SPEECH disturbances, AGRAFIA, and FINGER agnosia may occur when the
tumor involves the DOMINANT hemisphere.
Ø ON TEMPORAL LOBE TUMORS:
- particularly in the NONDOMINANT hemisphere, often produce FEW EARLY
symptoms but may cause convulsive SEIZURES
- A tumor deep in the temporal lobe may cause CONTRALATERAL HEMIANOPIA,
COMPLEX PARTAIL seizures, or
convulsive seizures preceded by an OLFATORY AURA or VISUAL
HALLUCINATION of complex formed IMAGES.

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- Tumors involving the surface of the DOMINANT temporal lobe produce
MIXED EXPRESSIVE and RECEPTIVE AFASIA or dysphasia, chiefly ANOMIA
Ø ON OCCIPITAL LOBE TUMORS:
- usually cause a CONTRALTERAL QUADRANT defect or HEMIANOPIA in the
visual field with functional SPARING of the MACULA. Seizures may occur,
preceded by an AURA of FLASHING LIGHTS but NO formed images
Ø ON SUBCORTICAL TUMORS:
- commonly involve the INTERNAL CAPSULE and produce CONTRALATERAL
HEMIPLEGIA.
- They may invade any lobe of the hemisphere, producing corresponding
symptoms.
- THALAMIC invasion produces contralateral CUTANEOUS sensory
impairment.
- Invasion of the basal ganglia does not usually produce parkinsonian
symptoms but occasionally produces athetosis, bizarre tremors, or
dystonic postures.
- Hypothalamic tumors may produce eating disorders or, in children,
precocious puberty
Ø BRAINSTEM TUMOR:
- are usually gliomas (usually astrocytomas).
Common symptoms, resulting from destruction of NUCLEAR masses, are
unilateral or bilateral PARALYSIS of the 5th, 6th, 7th, and 10th
CRANIAL nerves and PARALYSIS of LATERAL GAZE.
- Damage to the MOTOR or SENSORY pathways causes hemiparesis,
hemianesthesia, or cerebellar disturbances (eg, ataxia, nystagmus,
intention tremor).
- Intracranial pressure increases late and only when tumors obstruct
the aqueduct of Sylvius.
Ø POSTERIOR FOSSA TUMOR:
- including tumors of the 4th ventricle and cerebellum (usually
medulloblastomas, gliomas, ependymomas, or metastases), interfere with
CSF circulation and cause symptoms of INCREASED ICpressure early.
ATAXIC gait, INTENTION tremor, and other signs of cerebellar
dysfunction follow
Ø CEREBELLOPONTINE TUMOR:
- particularly NEURILEMMOMAS(acoustic neuromas, schwannomas), are
characterized by TINNITUS, unilateral hearing impairment, and sometimes
vertigo.
- If the tumor is LARGE, pressure on ADJACENT cranial nerves, brain
stem, and cerebellum produces loss of corneal reflex, facial palsy and
anesthesia, palatal weakness, signs of cerebellar dysfunction, and,
rarely, contralateral hemiplegia or hemianesthesia.
- Loss of vestibular response to caloric stimulation, enlargement of
the porus acusticus seen on imaging scans, and HIGH CSF protein content
suggest acoustic neuroma
Ø Nondominant parietal lobe lesions:
- contralateral astereognosis&sensory neglect, anosognosia,construction
apraxia,dressing apraxia,contralateral hemianopia or lower
quadrantanopia
Ø What tracts involved in Friedriech ataxia? What tracts in Vit B12
difficiency? Ans. the same tracts are involved in these 2 diseases: Vit
B12 diff and Friedriech ataxia (AR disease: progressive ataxia,
associated with pes cavus, DM, kyphoscoliosis, cardiomyopathy) dorsal
columns,lateral corticospinal tracts and spinocerebellar tracts.

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Ø damage to this nerve leads to loss of forearm pronation? Ans. Median
Ø the nerve of adductor pollicis? Ans. ulnar nerve
Ø 1) A 23 year old man with 10 year h/s of complex partial seizures and
pinkish macular rashes on his face..wht is the diagnosis..wht are these
rashes..wht is the inheritance pattern of the d/s?
2) A 47 year old had recently completed a course of chemotherapy for
his acute myeloid leukaemia some 6 days previously. The nurse in charge
asks you to examine the patient as he has noted the appearance of a
widespread petechiae. He is afebrile and his clotting is normal. wht
wud be the immed investigation and treatment..wht is the cause of these
petechiae?
3) A 40 year old house-wife was referred to the local neurologist for
investigation of dizzy spells and several episodes of loss of
consciousness. According to her husband, she had been well until 4
months before, since then he had noted 3 occasions when he found it
difficult to wake her up in the mornings. The GP was called in, but by
the time he arrived the patient was awake and complaining of a
headache. No obvious cause was found for these episodes. 1 month
previously, after drinking 2 Gin and Tonics, she became unusually
drowsy- this lasted for about 15 minutes. Following this, it was noted
that she became talkative, but was speaking nonsense for a further 5
minutes. Three weeks before admission she had an epileptic seizure
whilst at her daughter's wedding. There was no past medical history of
note, although she had gained 5 kg in weight in the last 3 months.
General medical examination was unremarkable. Pulse was 75/min SR, bp
130/85. Apart from her brisk tendon reflexes, neurological examination
was likewise unremarkable, with flexor plantars.
wht is the likely diagnosis?wht are the investigation?
Ans. ????
Ø ions have higher levels in CSF when compared to plasma? Ans. compared
to serum,CSF has the same concentration of Na+,
higher Mg++,Cl
and lower K+,Ca++,HCO3,Glucose,Protein
Ø the location of Locus coeruleus?and related neurotransmitter? Ans.
just lateral to the floor of 4th ventricle,yes NE
Ø CNS structures without BBB(Blood Brain Barrier)? Ans. choroid plexus
and also median eminence,neurohypophysis,lamina terminalis,pineal
gland.
Ø the presentation of conduction aphasia? Ans. poor repetition, good
comprehension, fluent speech…yes!paraphasias(use of incorrect
words),poor object naming,severe deficit of repetition and
fluent speech is often indirect(circumlocutory).
Ø Name the tissue that does not utilize glucose as the primary fuel
source. What does it utilize then? Ans. cardiac beta oxidation of fatty
acids....
Ø Wernicke’s aphaia sometimes misdiagnosed as psychosis,why? Ans. bcoz
they usually have no hemiparesis,no depression,instead euphoric,absence
of neurologic signs plus bizarre speech and ab
behavior,agitation,paranoid thoughts that sometimes seen, lead to
incorrect diagnosis of functional psychosis
Ø WHERE IS THE CHEMORECEPTOR TRIGGER ZONE LOCATED?
PONS
3RD VENTRICULE
4TH VENTRICULE
FRONTALE LOBE
MEDULA ans. rostral ventrolateral medulla...
Ø

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HISTOLOGY
Ø Call-Exner bodies:Granulosa/theca cell tumor of ovary
Councilman bodies:Hepatitis:toxic or viral
Cowdry type A bodies:HSV,SSPE
Russel bodies:Multiple myeloma
Mallory's bodies:Chronic alchoholic hepatitis
Schiller-Duval bodies:Yolk Sac tumor
Ø SOME HIGH YIELD NOTES FOR CELL BIOLOGY & HISTOLOGY, CELL AND TISSUE
BIOLOGY
INTRODUCTORY STUFF
DYES:
Dye Structure:
Chromophore Group: The chemical moiety of the dye that is responsible
for its color.
Auxochrome Group: The moiety on the dye that binds to the cellular
components. It is usually either amino or SO42- groups.
Amino auxochrome group = a basic dye.
Sulfate auxochrome group = an acidic dye.
Common types of stains:
Hematoxylin and Eosin (H&E): Most common type of stain.
Hematoxylin: Functionally a basic dye (despite the fact that it is
anionic). It binds to basophilic (negatively charged) nuclear
components like DNA and RNA.
It stains blue
Eosin: Acidic dye. It binds to positively charged, acidophilic
components.
It stains pink to red.
Masson (Trichrome) Stain:
Collagen is green.
Elastic fibers are red.
ACIDOPHILIC: Attracted to acidic substances, which are anionic
(negatively charged) at physiologic pH. Thus acidophilic substances are
positively charged.
Proteins are acidophilic in at a pH higher (more basic) than their
isoelectric point. When the environmental pH is above a protein's
isoelectric point, the protein is positively charged and hence
acidophilic.
Many proteins are acidophilic at physiologic pH.
Acidophilic Components:
BASOPHILIC: Attracted to basic substances, which are cationic
(positively charged) at physiologic pH. Thus basophilic substances are
negatively charged.
Proteins are basophilic at a pH lower (more acidic) than their
isoelectric point. When the environmental pH is below a protein's
isoelectric point, the protein is negatively charged and hence
basophilic.
Basophilic Components:

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DNA and RNA = basophilic due to presence of phosphate groups.
Proteoglycans = basophilic due to sugars and esterified sulfates which
are negative at physiologic pH.
Special Types of Staining Techniques:
Metachromasia: A substance can take on a different than expected color
when the substance has two chemically reactive groups that interact due
to their close proximity.
Fat-Staining: To stain membranes and lipid-materials, you must use a
fat-insoluble solvent and freeze-fracturing. You can't use paraffin
because it would dissolve the substance!
Common solvents include propylene glycol, and ethanol.
Sudan IV is a typical fat-soluble dye.
The Schiff Reagent -- specific for DNA and polysaccharides.
Feulgen Reaction: This reaction uses Leucofuchsin as a dye, which
selectively stains purines in DNA.
Periodic Acid-Schiff (PAS) Reaction: Selectively stains polyhexoses and
hexosamines. Tissues stained by this reaction include:
Glycogen
Epithelial mucins in goblet cells.
Proteoglycans in basement membranes -- but not of the CT matrix.
Enzymatic Staining: For example, you can visualize mitochondria by
testing for the product of a mitochondrial enzyme. The important point
is that the enzyme is not stained directly in these procedures. Rather,
the localization of its activity is tested for.
Immunohistochemistry:
Fluorescent Antibody Technique: Complex a fluorescent dye with an
antibody that binds to specific antigens on tissues that you want to
visualize.
Indirect Immunofluorescence: Visualization of a tissue using two
antibodies, where the target structure that is actually visualized is
bound to the second antibody.
Indirect Immunocytochemistry: Similar to indirect immunofluorescence,
but eliminating the need for fluorescent visualization.
Protein-A Gold Technique:
Autoradiography: beta-electrons interacting with silver bromide (AgBr)
crystals from radioactive materials illuminates radioactive structures.
Electron Microscopy:
Staining is usually with osmium.
Some sort of fixation is required -- such as Freeze Fracture, in which
we cut a preparation into thin slices using a microtome.
PLASMA MEMBRANE AND BASIC CELLULAR STRUCTURES
FLUID MOSAIC MODEL:
RED-BLOOD CELLS GHOSTS: Put a RBC in salt and crack the membrane (i.e.
make it leaky) so that all contents leak out. Then reseal the membrane,
and we are left with topography maps of the RBC-membrane, showing
peripheral and integral membrane-proteins.
Integral Proteins:
Glycophorin: Has extensive saccharide groups on the exterior surface.
It is a single-pass protein.
Band-III: Peripheral anion channel, exchanging HCO3- out for Cl- in.
It is a multi-pass integral membrane protein.

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Band-III has no lateral mobility in the membrane -- it is hooked
directly to the cytoskeleton via Ankyrin ------> Spectrin ------> Actin
spokes.
Rhodopsin: The "mother" of the 7-pass alpha-helical multi-pass
transmembrane protein (of the adrenergic G-protein-bound receptor
family). This is a general class of integral proteins and describes a
lot of different proteins.
Peripheral Proteins
Ankyrin is connected to the inside periphery of the RBC membrane.
Spectrin is hooked to membrane via Ankyrin.
Spectrin forms a lattice network composed of alpha and beta dimers.
It hooks onto Band-III in the membrane (via ankyrin) at one end, and
onto Actin at the spokes of the RBC-cytoskeleton in the RBC interior.
Band 4.1: Another peripheral protein that helps anchor spectrin and
actin to the RBC membrane.
Hereditary Spherocytosis: Hemolytic anemia caused by a failure for
RBC's to form a biconcave disc and therefore inability to squeeze
through capillaries.
It can be caused by any of a number of genetic mutations in RBC
cytoskeletal proteins.
One form is caused by a mutation in Ankyrin which results in bad
splicing. There is a 2.1 and 2.2 splice out of the same precursor mRNA.
2.1 splice: predominant in developing cells.
2.2 splice required in mature cells.
The 2.2 splice disappears with the missplicing mutation, hence RBC's
mature but they don't function when fully developed.
At the same time, other ankyrin isoforms of the same RNA precursor are
translated normally, but they are in other cell-types.
GLYCOSYLATION:
N-Linked Glycosylation
Sugar hooks onto Asparagine Residue.
Common Sugars attached are N-Acetylglucosamine (GluNAc), and Mannose
Glycosylation occurs cotranslationally, in the Rough ER.
PROCESS:
Core Glycosylation event occurs initially. It involves the linkage of
the core oligosaccharide.
The core oligosaccharide is then associated to the lipid complex,
dolichol phosphate. Then it is disassociated and linked to the protein
in one step.
O-Linked Glycosylation
Sugars hook onto Serine or Threonine residues.
Common sugars attached are N-Acetyl Neuraminic (Sialic) Acid and NAcetylgalactosamine.
Glycosylation occurs posttranslationally, in the Golgi.
Experiments to Demonstrate the Fluid-Mosaic Model: Lipids can move
laterally and can wiggle their hydrophobic tails very rapidly, but they
can't flip-flop without a special catalytic reaction (catalyzed by
flippase).
Heterokaryon Experiment: Showed the movement of membrane proteins
within the plasma membrane of a human-mouse hybrid.
Fluorescence Recovery After Photobleaching (FRAP): A way to show that
lateral movement of membrane proteins occurs.
You can determine a Diffusion Coefficient for Lateral Mobility. Some
common coefficients:
Phospholipids in membranes: 1 x 10-8 cm2/sec

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Most highly mobile membrane protein (Rhodopsin): 5 x 10-9 cm2/sec
You start with 100% fluorescence in membrane, then zap with bleach a
little spot on the membrane, and the fluorescence goes way down to
about zero.
Then you can watch the fluorescence recover (back up to near 100%) as
adjacent lipids and/or proteins diffuse to the bleached area.
Restricted Mobility: The cytoskeleton in red blood cells restricts the
mobility of many membrane proteins on the RBC membrane.
Cytoskeletal Elements: Filament Type Size Composition
Microfilaments 7-8 nm Actin monomers
Intermediate Filaments 10 nm variable
Microtubules 25 nm alpha and beta tubulin monomers
Myosin (Thick) Filaments variable Myosin
Microtubules:
Made of dimers of alpha and beta tubulin. They will self-assemble
(autopolymerize) under the right conditions.
Polarity
(+)-End: Tubulin monomers are, on average, being added to this end. New
monomers are put on at a faster rate than they fall off.
(-)-End: Tubulin monomers are, on average, being removed from this end.
Monomers fall off at a faster rate than they are put on.
Microtubule Organizing Center (MTOC): Often found around centrioles.
Microtubules hook to centrioles by their (-)-ends.
Tread milling Effect: If you label one monomer on a microtubule, it
will appear as if it magically moves from the plus to the minus end.
That's because we keep adding new monomers to the plus end, so it gets
pushed further back in the chain, until finally it is all the way
toward the minus end and it falls off the chain.
Anti-Microtubule Drugs:
Colchicine: Binds to tubulin monomers and thereby prevents assembly of
microtubules, killing the cell.
Taxol: Controversial new anti-cancer drug that works in the exact
opposite way as traditional drugs. It stabilizes the microtubule
filament so that it can't disassemble. The result is the same, however:
microtubule dynamics are lost and the cell dies.
CYTOSKELETAL MOTOR PROTEINS: ATPases that cleave ATP to cause movement.
The microtubules / actin don't move themselves. Rather it is the
interaction of the motor proteins with the tubules that causes
movement.
Myosin: Actin-binding protein.
Dynein: (-)-End Oriented Microtubule binding protein.
It moves along the microtubules from the (+) to the (-) end. It
therefore facilitates retrograde axonal transport.
Tail is the region that attaches to the microtubules. The Head is the
ATPase region.
Kinesin: (+)-End Oriented Microtubule binding protein.
It moves along the microtubules from the (-) to the (+) end. It
therefore facilitates anterograde axonal transport.
Cilia/Flagella: The minus end is toward the tip, and the (+)-end is
toward the basal body, toward the plasma membrane.
INTERMEDIATE FILAMENTS: Made of keratins, desmin, vimentin, and
neurofilaments.

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NUCLEAR TARGETING of PROTEINS:
Nuclear Pores: Have specific targeting signals for nucleus-bound
proteins. Pores are formed at points where the inner and outer layers
of the Nuclear bi-membrane come together.
EXPT: The Large-T Antigen of the SP40 virus was seen in the nucleus of
a host cell by immunocytochemical imaging.
A mutation on the T-Antigen site, exchanging a Lysine for a Threonine,
caused sorting to occur in the cytosol instead.
Thus this mutation was part of the Nuclear-Targeting Sequence.
EXPT: Frog oocytes -- the results suggested that the nuclear targeting
sequence was on the tail subunit of the nucleoplasmin protein in frog
oocytes.
When the head and tail were dissociated, the tail was able to through
nuclear membrane and head wasn't.
Also, if colloidal gold particles are associated with this tail
subunit, they, too, can get into the nucleus, but only if ATP is
present.
SUMMARY:
Transport into the nucleus does not take place by passive diffusion. It
takes by highly specific transport with targeting sequences.
It appears that nuclear transport is an active process (at least in
frog oocytes). It requires ATP.
ROUGH ENDOPLASMIC RETICULUM: Cytosolic proteins can be synthesized on
free ribosomes instead of the Rough ER, per se. However, the following
proteins are always synthesized on the Rough ER:
Membrane Proteins: Using Signal Peptides and Signal Recognition
Particles, they are directly translated into the membrane, where they
stay.
Secreted Proteins: They are exuded into the ER lumen, and then onto
Golgi and finally secreted in vesicles. They must be synthesized on ER
therefore.
MITOCHONDRIA: Proteins destined for the mitochondria are integrated
into the mitochondrial membrane post-translationally. First they are
synthesized, and then they go to mitochondria via a vesicle.
GOLGI COMPLEX:
Cis Golgi: Earliest part of Golgi, closest to the ER.
Transition Vesicles often transport material from the ER to the Golgi.
Middle Golgi
Trans Golgi: Part of Golgi off of which vesicle bud.
ENDOCYTOSIS: Clathrin associated with a receptor protein, which in turn
associated with the membrane.
There are several adapter proteins, depending on the membrane to which
the vesicle will fuse. For example, there is a specific adapter protein
for the Golgi.
The difference in adapter proteins between
LYSOSOMAL STORAGE DISEASES: Lots of diseases have at least one etiology
where the mutation lies in incorrect sorting of the protein, rather
than a non-functional protein itself.
I-Cell Disease:

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The Mannose-6-Phosphate recognition marker is found on one of the NLinked Oligosaccharides of a lysosomal hydrolase. It targets the
protein for the lysosome. Adding the M6P is a two step process.
One enzyme puts on N-Acetylglucosamine phosphate onto a mannose
residue.
A second enzyme then removes the N-Acetylglucosamine, leaving Mannose6-Phosphate in its wake.
It is the first step, addition of N-Acetylglucosamine phosphate, that
goes wrong in ICell disease.
Cystic Fibrosis:
The CFTR protein is mostly getting made, but it is not getting
transported to the Golgi. The primary etiology of the disease is a
sorting problem, not a defective protein.
Tay-Sach's Disease:
Again, one of the causes is a missorting of the protein betaHexosaminidase, where it can't get from ER to Golgi.
Emphysema and Familial Hypercholesterolemia are two more examples.
Sucrase-Isomaltase Deficiency:
The Sucrase-Isomaltase enzyme is normally targeted to the apical
epithelial membrane and is involved with disaccharide / glycogen
breakdown.
Individuals with the defect can't metabolize long-chain sugars.
Again it seems that the secretory pathway for the enzyme is blocked.
EPITHELIA
EPITHELIAL CELL TYPES:
Simple Squamous Epithelium: Kidney Bowman's Capsule
Resemble fried eggs in shape.
Simple Cuboidal Epithelium: Kidney Collecting Tubule
Kidney tubules cells are specialized for absorbing salt and water in an
apical to basal direction.
Simple Columnar Epithelium: GI Tract (Stomach, Jejunum, Duodenum,
Ileum)
Other Tissues: Gall Bladder and Uterine Gland.
Simple Columnar Cells are specialized for one or all of three things:
Secretion
Protection
Absorption: This is especially true in Duodenum and Jejunum.
They have oval nuclei toward the basal side.
SIMPLE COLUMNAR EPITHELIUM CELL TYPES: There are four basic cell types
of simple columnar epithelia
Columnar
Fusiform
Basal
Goblet: = Modified columnar cells that synthesize and secrete mucous.
Stereocilia are "cilia" that don't move, but they are actually very
long microvilli specialized for absorption, and only visible at EM
level.
Pseudostratified Columnar Epithelium: Trachea and Upper Respiratory
Tract
The trachea is actually ciliated, but there are also non-ciliated
pseudostratified columnar epithelia.

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Example of Pseudostratified Non-Ciliated Columnar Epithelium: Male
Urethra
Stratified Squamous Epithelium: Salivary Glands, Skin, Vaginal Wall
There was no example of this in the carousels but only final testing
slide.
Stratified Squamous Keratinized: Layer of Keratin on top, as in Skin.
Stratified Squamous Non-Keratinized (Mucosal): No Keratin on apical
surface, as in Vagina and Mouth.
Stratified cells form the following layers:
Basal End: Cuboidal Cells that are proliferative.
Middle: Polygonal cells held together by desmosomes.
Apical End: Squamous Cells that are non-proliferative.
Stratified Cuboidal Epithelium: Sweat Duct of Skin
Transitional Epithelium: Urinary Bladder
The tissue appears to transform from 5-8 layers when empty, to 2-4
layers when the bladder is filled. The cells can squish together.
EPITHELIAL General Characteristics
AVASCULAR: Epithelial Tissue is generally avascular.
POLARITY: Epithelial cell have polarity.
The apical side often contains microvilli and faces the lumen of
whatever surface the epithelium lines.
Microvilli are characteristically found on apical domain. Actin
filaments are associated with the microvilli, forming the terminal web.
Cilia are found on apical membrane, in ciliated cells.
The basal side is opposite that. A basement membrane, consisting of a
basal lamina and reticular lamina, often underlies that.
The Na+/K+-ATPase pump is characteristically only found on the
basolateral membrane.
BASEMENT MEMBRANE: The basal lamina is visible only at the EM level.
The Basement Membrane, on the basal surface, is available at the LM
level and consists of the basal lamina plus the underlying connective
tissue.
MESOTHELIUM: Mesodermally derived epithelium that lines body cavities.
TERMINAL WEB: Visible network of actin filament on the apical end of an
epithelial cell.
JUNCTIONAL COMPLEX: The junctional complex keeps the apical and basal
sides of the epithelium separate from each other.
Zonula Occludens: Tight Junctions. They allow for selective passage of
particles, and they prevent particles from getting stuck between cells
or getting into the lumen.
Zonula Adherens: Also present at the junctional complex.
Macula Adherens: Desmosome. It goes all the way around the
circumference of the cell, like a belt or a spotweld.
TERMINAL BAR: Zonula Occludens + Zonula Adherens.
Gap Junction: Believed to mediate electronic coupling between cells.
Dye can squeeze through a gap junction to get one from cell to the
neighbor.
POLARITY EXPT: Cells lost their polarity by disassociating and then
reassociating cells such that they lose their intercellular contacts.
The Na/K ATPase pump occurs only on the basal membrane of the cell.
Viral EXPTs: You can also study the distribution of viral proteins to
study the host-cell's machinery, since the virus uses the host-cell's
machinery.

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People have watched where viral capsid proteins went when they
associated with the host plasma membrane.
The Influenza Virus only distributed proteins to the apical end of an
epithelial cell.
PATHWAYS for Explaining Polarity: Two alternative methods have been
figured out.
Targeting Mechanism where a class of vesicles specifically recognize
proteins on the apical domain. Hence some proteins will only merge with
membrane on the apical domain.
Transcytosis: Some evidence also suggests that proteins are initially
sorted in the basal domain, and then later transferred to the apical
domain via transcytosis.
EPITHELIAL EXOCRINE GLANDS:
Unicellular: Goblet Cells are unicellular exocrine glands.
Simple Tubular
Simple Branched Tubular
Simple Alveolar
Simple Branched Alveolar
Compound Tubular
Compound Alveolar
Compound Branched Tubular
Compound Branched Alveolar
THE CELL CYCLE
Types of Cells Cycles:
Chromosomal Cycle
Centrosomal Cycle: The Centrioles duplicate themselves prior to
mitosis, and move to opposite poles.
Cytoplasmic Cycle: Refers to cytokinesis. Distribution and
redistribution of cytoplasm.
Phosphorylation Cycle: Phosphorylation promotes mitosis, as discussed
later.
Nuclear Membrane Cycle: Nuclear Lamins are phosphorylated during
Prophase, which causes them to dissociate and results in breakdown the
nuclear membrane.
Nuclear lamins are a form of intermediate filament.
Nuclear Lamins are dephosphorylated during telophase, so they
reassociate and membrane reforms.
CENTROSOMES: They divide into two before mitosis.
They form the Microtubule Organizing Center, out of which the mitotic
spindle grows, during mitosis.
MITOSIS:
Prophase:
Nucleoli disappear
Centrosomes split and each daughter forms an aster.
Prometaphase
The Nuclear Envelope breaks down.
Microtubules from each centrosome start interacting with the
chromosomes.
Kinetochore Microtubules from the centromere of each chromosome mature
and attach to some of the spindle microtubules.
Metaphase
The Kinetochore microtubules align the chromosomes along the metaphase
plate.

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The chromosomes are held in place by the opposed kinetochores and their
associated microtubules.
Anaphase
Kinetochores on each chromosome separate, allowing each chromatid to be
pulled toward the poles.
Anaphase-A: Kinetochore Microtubules shorten. Since the plus end of
these microtubules is right at the centromere, this shortening causes
the chromosomes to be pulled toward the poles.
Anaphase-B: Polar Microtubules elongate. The plus end of the polar
microtubules face the equator too, but this elongation somehow aids in
pulling (or pushing) the poles apart.
Ca+2 seems to play a role in promoting anaphase. There is high Ca+2
concentration during anaphase.
Telophase:
Daughter chromatids reach the poles.
Kinetochore microtubules disappear.
Nuclear envelope reforms as nuclear lamins reassociate, condensed
chromatin expands, and nucleoli reappear.
Involves dephosphorylation of many proteins.
Cytokinesis.
Actin and Myosin pinch the cell and form a contractile ring.
Organelles and cytoplasm are distributed evenly.
KINETOCHORES: Protein masses that form at the centromeres during
mitosis, and to which kinetochore microtubules attach.
SCLERODERMA: These patients produce auto-antibodies that react
specifically with kinetochores.
The Kinetochore Microtubules elongate toward the chromosome! They have
their plus-end facing the chromosome, hence they shorten during
chromosome separation.
Both Kinetochores must be attached for the separation to occur. This is
a biological safeguard to assure that nondisjunction does not occur.
CELL FUSION EXPERIMENTS: They provided evidence for activators that
promoted mitosis and DNA Synthesis. Cells in different stages of the
cell cycle were fused together to see what would happen.
G1 Cell + S Cell: G1 Cell immediately goes into DNA-Synthesis.
This is because the S-Cell had S-Phase Activator, which promoted theG1
cell to go into S-Phase.
G1 Cell + G2 Cell: G1 will go through S-Phase as normal until it
reaches G2, then the two cells will go through mitosis together.
So, the G2 cell waits for the G1 cell to catch up with it.
This suggests that S-Phase Activator present in the S-Phase is no
longer functional in the G2 phase. This is important -- it prevents
polyploidy by not allowing cells to synthesize DNA twice!
G2 Cell + S Cell: Again, S-Phase cell catches up to G2 cell, then they
proceed through mitosis together.
This expt demonstrated that their was no S-Phase Inhibitor in the G2
cell, or else the S-cell wouldn't have completed mitosis.
Thus there must be some other explanation for why the G2 cell doesn't
undergo replication in presence of S-Phase Activator.
Any Interphase Cell + M-Phase Cell: The interphase cell will
prematurely enter mitosis, from any stage, resulting in an abnormal
cell.
This is mediated by M-Phase Promoting Factor (MPF), as below.

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DNA-DAMAGE: When G2 cells are irradiated, their entry into M phase is
delayed. They don't enter mitosis until their DNA-repair processes are
complete!
CELIAC DISEASE: Intestinal disease results from abnormalities in
intestinal epithelial cell division.
Cells normally divide at the crypt (basal) region of the cell -- not
the apical end.
For each dividing cell, one daughter will become an epithelial cell and
migrate toward apical surface, while the other will remain a crypt
cell.
In Celiac Disease, this process does not occur normally.
M-PHASE PROMOTING FACTOR (MPF):
Xenopus Oocyte MPF Levels:
Oocyte: MPF level is low, in order to freeze egg in prophase, and to
prevent mitosis.
Mature Newly Laid Egg: MPF Level is high
Early Embryo: MPF levels alternatively high in M-Phase and low in
Interphase.
STRUCTURE: It has two subunits
CYCLIN: The regulatory subunit. It is produced at a constant rate in
the cytoplasm.
CDC2: The kinase subunit. It phosphorylates targets to induce mitosis.
CELL DIVISION CYCLE:
Pre-MPF is an inactive form of Cyclin + CDC2 is sitting around in
cytoplasm.
Active-MPF is made by a combination of two things:
Kinase Cascade from signal transducers modifies the Pre-MPF in complex
reactions (multiple phosphorylations) to active MPF.
Cyclin levels accumulate in the cytoplasm, as cyclin is continually
made in many cell types.
Mitosis is induced by Active MPF, via the catalytic activity of the
cdc-2 subunit.
Active MPF also produces cyclinases -- cyclin degradation enzymes that
lower the levels of cyclin.
This inactivates MPF, until cyclin is resynthesized or until it
accumulates again in the cytoplasm
MUSCLE
SARCOMERE COMPONENTS:
Z-Disk: The union of two actin heads.
It demarcates the sarcomere.
At the Z-Disk, there is no myosin.
A-Band: The distance of one thick filament, consisting of two myosin
filaments.
I-Band: The distance from the end of one thick filament to the
beginning of the next thick filament.
During contraction, the I-Band becomes shorter.
The I-Band consists entirely of actin.
The I-Band marks the margins of two adjacent sarcomeres. Each I-Band
technically lies within two sarcomeres.
H-Zone: The distance from the end of one thin filament to the beginning
of the next thin filament.
During contraction, the H-Zone becomes shorter.
The H-Zone consists entirely of myosin.

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The H-Zone lies completely within the sarcomere, near the center of the
sarcomere.
ACTIN MYOSIN INTERACTION: In a myofibril, in cross section:
Six actins can interact with each myosin. Actins are in a hexagonal
array.
Three Myosins can interact, in triangular fashion, with each actin.
SKELETAL MUSCLE CONTRACTION: Myosin plays the role of an ATPase ActinBinding Motor Protein.
We will start with myosin bound to actin. When Myosin is bound to
Actin, ATP is bound to the myosin head.
With ATP bound, Myosin can then detach from the actin thin filament.
Once detached, the myosin is free to hydrolyze the bound ATP to ADP +
Pi. It hydrolyzes the ATP, and the ADP + Pi remain attached to the
myosin head.
The myosin then reattaches to the thin filament.
Reattachment leads to the release of the Pi group, which in turn
strengthens the interaction between the actin and myosin.
Power Stroke: With the ATP gone, the myosin head undergoes a
conformational change, causing the actin and myosin to move relative to
each other.
Then the myosin head releases the ADP.
Then Another ATP must bind to the myosin, in order for the myosin to
release from the Actin to start another cross-bridge.
If there is no more ATP, Rigor Mortis results, in which the muscle is
stuck in the contractile state, with myosin bound to actin.
REGULATION OF THE CROSS-BRIDGE CYCLE: Regulation is according to
intracellular levels of Calcium and is mediated by Troponin Complex and
Tropomyosin.
RELAXED STATE:
Tropomyosin is bound to the thin filament around its major groove, in
the absence of calcium.
The Troponin Complex is periodically bound to the thin filament such
that it blocks the interaction between Actin and Myosin.
CONTRACTED STATE
Calcium binds to the Troponin Complex, causing a conformational change
in Troponin-C.
Troponin Complex (Troponin plus tropomyosin) removes itself from the
thin filament as a result, such that Myosin can bind.
ORGANIZATION OF MUSCLE:
MUSCLE: A whole muscle is surrounded by an epimysium membrane.
It is composed of a bundle of fasciculi.
FASCICULUS: Each fasciculus is surrounded by a perimysium membrane.
It is composed of a bundle of myofibers.
MYOFIBER (MUSCLE FIBER): Each muscle fiber is surrounded by an
endomysium membrane.
It is composed of a bundle of myofibrils.
It is a very long and thin single muscle cell.
It has a sarcolemma plasma membrane, with an endomysium basement
membrane beyond that.

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MYOFIBRIL: A bundle of myofilaments, stacked neatly next to each other
such that the Z-Disc is lined up.
Every Thin filament in a myofibril can interact with 3 thick filaments.
Every thick filament in a myofibril can interact with 6 thin filaments.
Each Myofibril is bathed in sarcoplasm and surrounded by a sarcoplasmic
reticulum from whence it gets it calcium supply.
MYOFILAMENT: A very long, continuous series of sarcomeres, consisting
of actin and myosin.
Thin Filament: Actin
Thick Filament: Myosin
Intermediate Filament: Some muscle fibrils also have some intermediate
filaments.
SKELETAL MUSCLE CROSS-SECTION (Location of Nuclei): The nuclei are all
pushed to the periphery, because the actin/myosin fibers take up the
central part. Compare this to cardiac muscle, whose nuclei are in the
center.
CARDIAC -VS- SMOOTH MUSCLE: Cardiac muscle has nuclei centrally located
and relatively more cytoplasm than smooth muscle.
T-TUBULES: They run in the triad, with sarcoplasmic reticulum on either
side, in between each of the individual myofibrils. They transmit the
Ca+2 depolarization from the plasma membrane to the SR, which in turn
transmits it to all the fibers.
Ca+2 release from the SR initiates the muscle contraction.
Ca+2 is pumped back into SR to restore resting, by a Ca+2-ATPase.
NEUROMUSCULAR JUNCTION:
Active Zone: Electron-dense (dark in EM scan) patch of membrane at the
end of a nerve, right at the neuromuscular junction.
Note that vesicles are found right at the membrane, while mitochondria
are found more proximal, away from the active zone.
Junctional Fold is right opposite the active zone.
Ach Receptors on the muscle membrane are highly concentrated right at
the nerve terminal.

MUSCLE DEVELOPMENT:
Mesenchymal cells form myoblasts.
Myoblasts proliferate and form myotubes by fusing together, resulting
in a large multinucleate cell.
So, muscle becomes multinucleated by the fusing together of primitive
myoblasts.
SATELLITE CELLS: These cells lie squeezed in-between the endomysium
(basement membrane) of a myofibril and the fibers themselves.
Developmentally they have the same origin as myotubes. They are
myoblasts that did not fuse with other myoblasts during development.
FUNCTION = Muscle Repair. They proliferate to repair damaged muscle
tissue.
They will divide to regenerate muscle, but the regeneration may be
incomplete.
MUSCLE REGENERATION:

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When the muscle fibers are gone, all that is left is the basal lamina
and reticular formation of the endomysium.
The satellite cells then migrate into the empty endomysium.
Macrophages come in to remove necrotic remnants (debris)
Muscle regeneration may be incomplete (muscle atrophy or weakness).
Fiber Splitting can occur, where the satellite cell can generate
smaller duplicated myofibril sections from one original myofiber.
DUCHENNE MUSCULAR DYSTROPHY: Poor function and structure of skeletal
muscle.
Symptoms / Prognosis:
Hypertrophy of lateral thigh and calf, except that it is not muscle -it is fatty tissue.
Death by respiratory failure, usually due to infection and or
regurgitation.
Esophagus malfunction: The skeletal muscle portion of the esophagu1s
doesn't function right, leading to problems with swallowing and
regurgitation.
Upper third of esophagus: skeletal muscle
Middle third of esophagus: Transition of half skeletal and half smooth
muscle.
Lower third of esophagus: Smooth muscle.
Gower's Sign: Diagnostic test of ability to squat down and stand back
up.
Histopathology: You see necrotic muscle fibers, that ultimately fill
with fat infiltrates, giving the pseudohypertrophic appearance to the
muscle.
Pathology: Faulty Dystrophin Gene, resulting focal lesions on the
muscle membrane ------> Calcium leaks in the cell ------> perpetual
contraction ------> necrosis
You get contracted myofibers.
You get swollen mitochondria.
The fibers remaining (that are not necrotic) are spheroid.
GENETICS: X-Linked recessive disorder. It is passed from Mother to Son
(hemizygous) on the X-chromosome.
DMD Gene, coding for Dystrophin, is very large. Many of the mutations
are new mutations.
There are brain and cardiac isoforms of the Dystrophin protein.
Werdnig Hoffman Muscular Dystrophy: Variant wherein a small portion of
the dystrophin is missing. In DMD, a large portion is missing.
DYSTROPHIN: Function is to link the muscle fibers with the
extracellular matrix. It function in a spectrin-like fashion, to
connect the extracellular matrix with muscle actin. This provides
muscle membrane stability. Beyond that function is unclear.
TREATMENT METHODS:
Satellite Cell Replacement
They tried to inject donor satellites to provide donor dystrophin, but
the dystrophin couldn't get past the basement membrane barrier to get
to the membrane. Using collagenase for this purpose helped but didn't
increase muscle strength.
Viral Infection with the Correct Gene -- severe limitation here was the
huge size of the DMD gene.
Repair Point Mutations on mRNA -- Novel approach where they repair the
mRNA to get past the stop codon point, suppling an artificial amino
acid at that point.

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In-Vitro Screening: Extract cells from the embryo and test for a
particular exon on the DMD gene
If the embryo had the DMD gene, then a positive PCR product would be
obtained (i.e. some of the exons were not there).
If the embryo did not have the DMD gene, then a negative PCR product
was obtained, and they could reimplant the embryo for development.
PENNIFORM MUSCLE: Muscles with a central tendon, used for strength and
stability. Example = Transversus Abdominis.
FUSIFORM MUSCLE: Muscles with a tendon on either side longitudinally,
used for speed. Example = Biceps Brachii.
Ways of Distinguishing CARDIAC MUSCLE -vs- Smooth Muscle:
Cross-Section: Cardiac Muscle has a centrally placed nucleus, whereas
the nucleus is around the periphery in skeletal muscle.
Longitudinal Section: Cardiac muscle appears striated, but with
branches.
The cardiac cells are branched in longitudinal section.
The cardiac cells have the same structural units as skeletal muscle,
although SR and T-Tubules won't be as regular.
In Cardiac Cells you get a diad instead of a triad -- one SR membrane
will adhere with one T-Tubule.
INTERCALATED DISK: The junctional complex that separates cardiac muscle
cells. They always coincide with the Z-Line of muscle fibers.
Fascia Adherens is the basic structural connections between the two
cells.
They are similar to desmosomes but are only found in cardiac cells.
The Fascia Adherens apparently binds thin filaments in adjacent I-bands
to the plasma membrane of cardiac cells.
Desmosomes: The tightest point of connection between two cardiac cells.
Gap Junctions: Allows fast electrical conduction between two cardiac
cells.
CARDIAC ISCHEMIA:
Structural changes in ischemia:
15 minutes: Structure changes occur.
30-60 minutes: The cell can still recover.
> 60 minutes: The cell dies, necrosis.
Reperfusion Injury: Occurs when oxygen is suddenly replenished after
extended deprivation. It can cause mitochondria to swell up and
explode.
Histopathology of Cardiac Ischemia:
Chromatin is more condensed than normal.
Mitochondria swell
Glycogen stores are absent.
Unlike skeletal muscle, cardiac muscle cannot regenerate.
SMOOTH MUSCLE:
Histological Characteristics
Single central nucleus, but the amount of cytoplasm is less as compared
to cardiac muscle, i.e. the nucleus takes up a great space in the cell
in smooth muscle.
Cell is not striated, as actin and myosin are not arranged in linear
fashion.

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The amount of actin is greater than that of myosin. Actin is bound to
dense bodies in the cytoplasm, which are held in place by intermediate
filaments.
CONTRACTION:
RELAXED STATE:
Myosin thick filaments are sparse, i.e. they are not polymerized.
Myosin is dephosphorylated when relaxed.
CONTRACTED STATE:
Myosin Light Chain is phosphorylated.
Myosin forms more thick filaments
This allows the dense bodies to move toward each other.
PROCESS OF CONTRACTION / REGULATION
Calcium activates Calmodulin Complex.
Calmodulin Complex then activates the Myosin Light Chain Kinase (MLCK).
Myosin Light Chain Kinase then phosphorylates the myosin light chains
DOWN-REGULATION: Here are ways of inducing relaxation or lessening
contractile tonicity.
beta-Adrenergic transduction can phosphorylate the Light Chain Kinase,
thus deactivating it ------> No Phosphorylation of Myosin Light chains
------> Less contraction.
Phosphatases remove the phosphate from the myosin light chain to induce
relaxation.
ACTIN-BASED MOTILITY:
Pseudopod Movement: Cytoplasmic streaming as mediated by actin
polymerization and depolymerization. No myosin is involved.
Cytokinesis: Once again involves interaction of actin and myosin to
pinch the cell.
MICROTUBULE BASED MOTILITY: Dynein and Kinesin
Dynein is a minus-end protein. It travels from plus to minus and thus
aids in retrograde axonal transport.
Kinesin is a plus-end protein. It travels from minus to plus and thus
aids in anterograde axonal transport.
CONNECTIVE TISSUE
COMPONENTS OF CONNECTIVE TISSUE:
Fibers
Collagens
Elastic Fibers
Ground Substance (Proteoglycans)
Cells
Macrophages
Mast Cells
Fibroblasts
COLLAGEN: The primary fiber found in connective tissue. Although other
elastic fibers are also found.
Tropocollagen is the basic structural unit, consisting of three alphachains arranged in a helix.
Tropocollagen shows a typical banding pattern on EM, due to the
staggered helices. Procollagen doesn't show the banding pattern.
Chemistry:
Every third residue is glycine.
Hydroxyproline and Hydroxylysine are also prevalent.
Synthesis:

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Registration Peptide: The registration peptide, distinct from the
signal peptide, accomplishes two things.
It keeps the collagen helix soluble in the cell.
It allows the alpha-strands to align properly in the cell, in order to
form the helix.
alpha-strands are synthesized in the ER as usual. The signal peptide is
cleaved but the registration peptide, as above, remains.
Post-Translation Modifications:
Lysyl Hydroxylase and Prolyl Hydroxylase hydroxylate lysine and proline
residues.
Various glycosylations are done.
Procollagen is formed intracellularly. It is the soluble, spontaneously
formed helix that results from the individual strands, after posttranslation modifications are made:
Procollagen still has the registration peptides intact.
Procollagen is secreted.
Procollagen Peptidases then cleave the registration peptide
extracellularly, to result in Tropocollagen.
Tropocollagen then forms fibrils spontaneously, stabilized by crosslinks.
Lysyl Oxidase turns on Hydro lysine residues into aldehydes, to
stabilize cross-link formation.
Fibers form by the association of fibrils.
Collagen Types:
Collagen I: Skin + Bone
Collagen II: Cartilage
Collagen III: Aorta (Reticular Fibers)
These are also associated with elastic fibers
A silver stain will only stain reticular fibers, so they can be
identified.
Collagen IV: Basement Membrane
Basement membranes retain the registration peptide.
As a result they don't form fibers but instead form sheets.
COLLAGENASE: Breakdown of Collagen
Process of Collagen Degradation:
Collagenase is secreted as a proenzyme and is activated by other
proteases.
It cleaves at a specific site -- about 25% of the way down the
molecule.
The specific cleavage results in the spontaneous denaturation of the
collagen helix. The smaller pieces have a lower melting point and are
more volatile.
Other proteases then finish off the job.
Collagenase activity is temperature and fluid-dependant
REGULATION of COLLAGENASE:
Tissue Inhibitors of Metalloproteases (TIMPs): They bind only to
activated collagenases, thus moderating their activity through negative
feedback.
Extracellular Proteases: Three types of extracellular proteases aid in
the degradation of collagen:
Metalloproteases. Collagenase is a metalloprotease
Serine Proteases. For example -- elastase and thrombin
Cathepsins.
Collagen-related disorders
Ehlers-Danlos Syndromes: Hyperextensibility of skin and joints.

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Osteogenesis Imperfecta
Recessive Dystrophic Epidermolysis Bullosa: Too much collagenase.
Scurvy: Vitamin-C deficiency leads to malfunctioning prolyl
hydroxylase.
ELASTIC FIBERS:
Arrangements of elastic fibers: They can be arranged in three different
ways
Fibers / Fiber Bundles -- as in skin
Lamellae (sheets) -- as in vasculature
Fine Networks -- as in the lung
Protein Composition:
Microfibrillar Protein: Forms the underlying "scaffolding" over which
the elastin is laid.
Elastin: The amorphous, elastic material.
Elastin is resistant to degradation, except by elastase.
Desmosine and Isodesmosine: Cross-link elastin, forming a network, and
stabilizing the elastin during stretching and compressing.
Synthesis:
First, microfibrillar protein lays down the scaffolding.
Then, elastins get laid down on top.
AGING: Wrinkles occur as microfibrillar structure is lost
Emphysema: Loss of elasticity in lung. Rare form = congenital
malfunction of elastase in lung.
GROUND SUBSTANCE: Proteoglycans. They consists of a core protein +
Glucosaminoglycans
Glycosaminoglycans (GAGs): Linear polymers of repeating disaccharides
of hexosamine plus a uronic acid such as glucuronic acid.
GAG-residues are often sulfated.
SIGNALING FUNCTION:
GAGs have a high negative charge and are highly hydrophilic.
Basic Fibroblast Growth Factor (BFGF) can bind to proteoglycans to
promote the growth of fibroblasts.
In this capacity proteoglycans also act as a sieve controlling passage
of materials through the ECM. This property is especially important in
the kidney.
Aggrecan: Found in Hyaline Cartilage.
Perlecan: Found in Basement Membrane
Syndecan: Found in Epithelial Tissue. It remains attached to the plasma
membrane.
Hyaluronic Acid: Not associated with a core protein itself, but other
proteoglycans can associate with it.
Tissue Distribution:
Vitreous humor of eye.
Synovial Fluid of joints.
It facilitates cell migration during growth and repair.
Hyaluronidase is secreted when hyaluronic acid is no longer needed.
BASEMENT MEMBRANES: Made of the Basal Lamina + Reticular Lamina, or two
layers of basal lamina. It is visible at the light microscope level,
while basal lamina by itself is not.
Basal Lamina: It provides a substrate for epithelial cells. It consists
of different components:

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Lamina Rara: Primary constituent of the basal lamina, composed of two
proteins -- laminin and fibronectin. It is directly adjacent to the
epithelial cells.
It is electron lucent in the electron-microscope.
Laminin: Very large protein it three chains. There are specific binding
domains for collagen and heparin.
Entactin is often associated with Laminin.
CANCER: Laminin will hook to integrin receptors. In addition it may
have its own receptor, which acts in tumor metastasis.
Fibronectin: Two chains. It is important for wound healing and cell
migration.
There are three forms of fibronectin:
Plasma Fibronectin: Binds fibrin and fibrinogen, and plays a role in
blood clots.
Cell Surface Fibronectin
Matrix Fibronectin -- insoluble matrix fibrils.
Again, it has specific binding domains for heparin and collagen, and it
will hook into cellular integrin receptors.
Lamina Densa: The next layer, underneath the Lamina Rara. Composed
mainly of Collagen IV (basement membrane collagen) and Heparin.
It is electron-dense in the EM microscope.
Again, Collagen IV still has its globular registration peptide, so it
forms meshworks instead of fibers.
Heparin Sulfate interacts electrostatically with the Collagen IV.
Lamina Reticularis: The next layer down. Composed of Collagen III and
Collagen VII. This makes up the Reticular (elastic) fibers in some
basement membranes.
Collagen III is the main reticular collagen.
Collagen VII acts as an anchor, to hold the reticular fibers to the
basal lamina.
FNXN: The reticular lamina connects the basal lamina to the underlying
stroma.
Basement Membrane: The very bottom layer of the epithelial layer.
Integrins: Epithelial Cellular receptors that allow the cells to
interact with the basement membrane.
STRUCTURE: Integral membrane heterodimeric proteins, with alpha and
beta subunits non-covalently linked.
Ligand-binding Domain: Binds to a specific sequence on laminin and
fibronectin in the extracellular matrix.
The specific sequence is Arg-Gly-Asp (RGD)
Intracellular Attachment: The protein is attached to the actin
cytoskeleton, via the following anchor proteins:
Talin
Vinculin
alpha-Actinin
FUNCTION: Integrins mediate cellular adhesion and migration through the
ECM.
LEUKOCYTE MIGRATION: Part of the inflammatory response.
Selectins: Specialized glycoproteins on endothelial cells, that serve
to attract leucocytes to that location when activated.
They allow for stronger interaction of the ECM with the leucocyte
integrins.
C:ell Adhesion Molecules (CAMs) After being attracted by selectins, the
leucocytes interact with CAMs on the endothelial surface.
The leucocytes binds to the endothelial cell CAMs.

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Activated leucocytes must then secrete proteases and collagenases to
migrate through the vessel wall and go to the site of infection.
WOUND HEALING:
Plasma Fibronectin binds to the blood clot, thus causing Platelet
Derived Growth Factor to be released by the platelets.
PDGF, along with C5a, then attract neutrophils and macrophages.
Macrophages then secrete proteolytic enzymes for fibroblasts and smooth
muscle cells, so they can get through the debris.
Then the matrix is restored by fibroblasts, then the endothelial cells
are restored.
TUMOR METASTASIS: Some tumor cells secrete collagenase, thus breaking
down basement membranes and allowing the metastatic cells to penetrate
the blood vessels.
FIBROBLASTS: RESIDENT (always present) Connective tissue cells that
synthesize collagen, elastin, and basal lamina.
Fibroblasts are not the only cells that synthesize this stuff.
Epithelial tissues and smooth muscle cells can make their own ECM, too!
Histology:
They have little cytoplasm and lots of ER and Golgi, which is what we'd
expect for their synthetic roles.
Fibroblast Activating Factor up regulates ECM production in
fibroblasts.
Lymphocytes and monocytes can secrete fibroblast activating factor
toward this end.
ADIPOCYTES: A RESIDENT CELL in connective tissue -- i.e. it is always
present.
White Adipose Tissue: Efficient, low-density storage form for energy.
It is highly vascularized and innervated.
HISTOLOGY: Big lipid droplet with nucleus plus minimal cytoplasmic
components all off to one side.
Lipid Deposition (Anabolic): Lipoprotein Lipase frees two of the three
fats from triacylglycerols from chylomicrons in the blood.
The lipoprotein lipase is located in the vascular endothelium.
The remaining monoacylglycerol stays in the blood and goes back to
liver.
The two freed fatty acids diffuse through the capillary endothelium -----> basal lamina ------> connective tissue ------> adipose basal
lamina ------> adipocyte ------> and into the adipose tissue.
Lipid Mobilization (Catabolic): Hormone Sensitive Lipase is activated
via the beta-adrenergic pathway. It frees fatty acids from
triacylglycerols in the adipose tissue.
beta-Adrenergic Pathway means that Hormone Sensitive Lipase is
phosphorylated to be activated (via cAMP ------> Protein Kinase, etc.)
Brown Adipose Tissue: Specialized for thermoregulation.
It is present in hibernating and newborn humans, but not in human
adults.
Uncoupling Protein uncouples the oxidation of Acetyl-CoA in adipocyte
mitochondria, such that no ATP is produced. Instead, the generated
electrochemical gradient is dissipated as heat.
OBESITY:
Hyperplasia of adipocytes occurs after birth, but the adult doesn't
gain or lose adipocytes appreciably. Obesity occurs by hypertrophy of
adipocytes.
Body Mass Index = (Weight (kg)) / (Height (m))2

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Healthy BMI is 23-28.
Two forms of obesity:
Android Obesity, weight in upper body and abdomen, is correlated with
risks for CHD.
Gynecoid Obesity, weight in hips and thighs, is not correlated with
risks for CHD.
"Reduced Obese": When an individual gains weight and then loses it
again, several things change physiologically which make it difficult to
keep off the weight:
Metabolic needs go down from the original baseline level -- i.e. total
daily caloric requirements go down after having lost weight.
Upregulation of adrenoreceptors occurs -- making it easier to mobilize
fatty acids from adipose tissue (that is actually good news).
BUT, there is a decreased response to hypoglycemia -- catecholamines
aren't released as readily.
LEPTIN: A protein made by adipocytes that correlates with obesity in
laboratory mice
EXPTs in mice suggested that obesity might be due to a lack of leptin.
Mice that were obese had no leptin.
Unfortunately this did not hold the same for humans. Obese humans
actually had more leptin, so there was a positive correlation.
There appears to be Leptin receptors in the hypothalamus, which will be
involved with hunger regulation.
They have also found leptin receptors in the choroid plexus of
ventricles.
ADIPSIN: It forms Acyl-Stimulating Protein (ASP) which generally
promotes the building of triacylglycerols.
Many obese patients have elevated adipsin levels, meaning that they can
make fats readily but they have normal or subnormal rates of mobilizing
them.
Tumor Necrosis Factor: Obese patients also seem to have elevated levels
of this factor. This is related to development of insulin resistance.
MAST CELLS: TRANSIENT Connective Tissue Cell. They function in allergic
reactions.
They respond to IgE from plasma cells.
Histology:
They characteristically have cytoplasm full of dark-staining granules.
Mast Cell Granules are released in an allergic reaction. They contain:
Heparin, an anticoagulant.
Histamine, vasodilates small vessels, causing increased microperfusion
of the tissue (i.e. redness)
Serotonin
Leukotrienes
MACROPHAGES: TRANSIENT Connective Tissue Cell. They are derived from
monocytes circulating in the blood.
Phagocytosis is often mediated by IgG
Histology:
Can be distinguished from other transient cells because they usually
have foreign materials ingested.
They have numerous small lipid droplets (vacuoles)
PLASMA CELLS: TRANSIENT Connective Tissue Cell. They secrete
antibodies.
Morphology / Histology:
They have a clock-face nucleus.
They have a perinuclear clear area.

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Ø

EMBRYOLOGY
v Germ layer Subdivision Derivatives
Epidermis
---------------Skin glands, hair, nails
Nasal epithelium
Ectoderm Surface Oral epithelium and tooth enamel
Adenohypophysis
Lens of eye, cornea
Inner ear
Neural tube Brain: neurohypophysis, cranial motor nerves, epiphysis,
optic nerve and retina
Spinal cord: spinal motor nerves
Cranial crest derivatives: sensory ganglia, parasympathetic ganglia,
glial and Schwann cells, leptomininges, melanocytes, carotid body and
parafollicular cells, many bones of face and cranium, visceral
cartilages (throat), connective tissue, minor muscles, carotid body,
odontoblasts, thyroid, parathyroid, thymus, salivary and lacrimal
glands, outflow tract of heart, cardiac semilunar valves, walls of
aorta and aortic arch derived arteries, ciliary muscles, cartilage of
external ear
Neural crest Trunk crest derivatives: spinal ganglia, parasympathetic
ganglia, parasympathetic ganglia, satellite and Schwann cells,
melanocytes, adrenal medulla
------------------------------------------------------------------------------Mesoderm
--------Somites(Paraxial) Connective tissue of skin
Skeletal muscles
Axial skeleton
Intermediate Kidneys
Genital structures
Renal and genital ducts
Lateral Somatic: connective tissue of ventral body wall, parietal
peritoneum, blood vessels, limbs
Splanchnic: adrenal cortex, visceral peritoneum, heart, blood vessels
------------------------------------------------------------------------------Endoderm
---------Digestive tube
Respiratory epithelium
Digestive glands
Pharyngeal glands
Eustachean tube and lining of middle ear
Urinary bladder
HIGHLIGHTS OF THE EMBRYONIC PERIOD: (WEEKS 3-8)

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---------------------------------3rd week-- primitive streak, notochord, gastrulation, neural folds,
early somites
4th week --closure of neuropores, somites, otic pits, branchial arches,
limb buds, tail, folding begins, heart is distinct
5th week --growth of head, cervical sinus, hand plates, optic cup
6th week -- external acoustic meatus, prominent cervical flexure,
digital rays in hand
7th week-- digital rays in foot, umbilical herniation, yolk sac
8th week-- unquestionably human, genitalia indistinct
At the end of 8th week all systems are formed
Monthly Periods of Fetal Development
-----------------------------------Developmental events of the third through the ninth months (week 9
through week 38).
Weeks 9-12--- urine formed, genitalia distinct, hepatic erythropoiesis
ends, head is 1/2 size of fetus, fine hair appears
Weeks 13-16-- ovaries differentiated, splenic erythropoiesis begins,
eyes, ears, and nose almost normal appearance, bile is secreted
Weeks 17-20--- fetal movements (quickening), vernix caseosa, lanugo,
brown fat, uterus and testes form, fetal heartbeat can be heard with a
stethoscope.
Weeks 21-24--- respiratory system begins surfactant production, rapid
eye movements, skin is wrinkled, blink-startle reflex, fingernails,
surfactant
Weeks 26-28--- respiratory system matures, splenic erythropoiesis ends,
eyelids separate
Weeks 29-32--- pupillary reflex
Weeks 33-38 --testes descend, bone marrow hematopoiesis, fetus orients to light
v Recall: Derivatives
- review:
1-derivatives of telencephalon:cerebral
Hemispheres,Hippocampus,Amygdaloid,Putamen,Olfactory
bulbs,Claustrum,CAUdate,Lamina terminalis:HHAPOCCL:HHeredity
Adenomatous POlyposis CCAULi
2-derivatives of
diencephalon:thalamus,subthalamus,hypothalamus,epithalamus(every word
with thalamus!)
Neurohypophysis,Mamillary bodies,pineal Gland,Globus
pallidus:NMGG(NeuroMascular GGunction!)
iris,ciliary body,retina,(optic nerve,chiasm and tract):all related to
eye!
Ø Urinary System Questions
The pronephros is the first kidney and is developed from intermediate
mesoderm, somites 7-14. It is vestigal in humans. The mesonephros is
the second kidney, and functions in fetal life before the metanephric
kidney is formed and functioning. It’s duct, the mesonephric duct,
forms as an extension of the pronephric duct. The mesonephric duct
eventually becomes the vas deferens in the adult male, while the
mesonephric tubules become the efferent tubules.
The ureteric bud gives rise to the collecting system of the metanephric
kidney, while the cap gives rise to the filtration portions (nephrons).
Both of these arise from intermediate mesoderm.

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Unilateral renal agenesis will cause the other kidney to become much
larger, while bilateral agenesis will lead to oligohydramnios. The
increased pressure and decreased volume of amniotic fluid in the
placenta will cause Potter’s fascae, and pulmonary hypoplasia.
Early bifurcation of the ureteric bud will cause bifed ureter, while
late bifurcation will cause bifed pelves into a single kidney. An extra
ureteric bud will lead to a supernumerary kidney or a large, fused
kidney.
Ectopic ureters in the bladder open along the edge of the trigone
region. They can sometimes open into the vagina or urethra, causing
incontinence. The ureter feeding the superior kidney enters into the
inferior, ectopic position.
Multicystic kidneys lead to incomplete development of calyxes and
primitive ductal development. Polycystic kidneys are caused by a
recessive genetic disorder, leading to problems with differetiation of
renal cells, not problems with collecting portions of the kidney.
A horseshoe kidney is caused by problems with ascension and rotation of
the kidney. It results in a large, fused kidney present in the pelvis.
It’s ascent can by blocked by the inferior mesenteric artery, leading
to problems. Failure to ascend can also lead to ecotopic kidney,
present in the pelvis. Usually this causes no problems.
The renal blood supply ascends along with the kidney, and new arteries
are created as older ones more caudally are reabsorbed. In the case of
a pelvic or horseshoe kidney, arteries will arise from the lower part
of the aorta.
Ureterocoele occurs when ectoderm from the UG sinus overgrows and
occludes the ureteric opening. This tends to occur after the
mesonephric ducts have been absorbed into the bladder, creating the
trigone region, which is made from intermediate mesoderm. The rest of
the bladder is made from splanchnic mesoderm, and the entire thing is
lined with endoderm. When this endoderm overgrows the ureteric openings
ureterocoele occurs. Posterior urethral valves occur when mucosal flaps
occlude the urethra near where the vas enters, causing occlusion.
The bladder forms from the cloaca after is partitioned by the urorectal
septum, and is made from splanchnic mesoderm. The trigone comes from
the absorption of the mesonephric ducts by the bladder.
The urachus is the remnant of the allantois, and connects the bladder
to the umbilicus. It becomes the median umbilical ligament, but if it
remains patent it can cause cysts, fistula, and sinuses.
Extrophy of the bladder is caused by a defect in the ventral wall,
exposing the trigone portion of the bladder. It is caused by nonclosure of the umbilicus due to a defect in mesodermal migration. It is
associated with epispadias because the dorsal surface of the penis does
not form properly.

Limb Development Questions

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A limb bud is an initial outgrowth from the embronic flanks, induced by
FGF-10. Later, the apical ectodermal ridge takes over, promoting growth
by releasing FGF-8 and later a number of FGF factors maintaining the
limb bud.
The zone of polarizing activity is present in the posterior mesoderm,
and causes the differential growth of the limb bud in the
anterior/posterior plane by releasing sonic hedgehog (Shh) protein. Shh
is maintain by FGF from the AER. This causes differences in expression
of various HOX genes, shifting their “stripes” from proximal/distal to
a posterior/anterior direction. I have no idea what the hell Rindler is
talking about here.
A child with mirror-image development of the foot could be explained by
the presence of two ZPA’s (??), or possibly a ZPA that was somehow
shifted to a dorsal/ventral axis (??).
The innvervation pattern of the dermatomes reflects the origin and
growth of the limb buds in that they show a rotation pattern.
Basically, the induction of the limb (whose bones come from lateral
mesoderm, and muscles from myotomes) is done by FGF-10, followed by P/D
grwoth maintained by the AER releasing FGF-8 and other FGF’s. P/D
differentiation occurs as a result of the clock mechanism of the
progress zone and it’s release of Msx (only found in the progress
zone). A/P differentiaton occurs because of Shh released from the ZPA,
which causes stuff to happen with HOX genes. D/V differentiation
results from the effects of WNT7a produced by the dorsal ectoderm and
Engrailed-1 produced by the ventral ectoderm. Dorsal mesenchyme creates
LMX1b, and leads to the formation of the nails and patella.

Hindgut Questions
The hindgut gives rise to the distal ½ of the transverse colon
(Intraperitoneal), the descending colon (Retroperitoneal), sigmoid
colon (I), rectum (R), and anal canal (R).
The pectinate line is important because it is the dividing point
between endoderm (from the former cloaca) and ectoderm, causes abrupt
changes in NV supply and types of muscle. The vascular supply changes
from IMA to the inferior rectal arteries, the innervaton changes from
autonomic (via symps from lumbar splanchnic nerve, inferior mesenteric
ganglion, superior hypogastric plexus, inferior hypogastric plexus,
parasym from pelvic splanchnics to inferior mesenteric plexus to
synapse in the rectal wall) to somatic (via the inferior rectal branch
of the pudendal nerve). Lymphatic drainage changes from the IMA lumbar
nodes to inguinal.
Abnormalities of hindgut formation:
Failure of the Rathke folds causes the UR septum near the anal membrane
to remain open, forming a fistula. In males, a rectoprostatic urethra

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fistula forms, while in females a rectocloacal fistula can result.
Rectovaginal or anovestibular fistula can also result. Basically, the
fistula will occur somewhere near the anal membrane.
Failure of both the Rathke folds and the UR septum leads to a
rectovesical septum in males (because there is no septum, the rectum
will join with the bladder, which is formed from the cloaca) and in
females, paired vaginas can result.
Malalignment of the folds leads to rectoprostatic urethra in males,
just as in the failure of the Rathke folds, but also causes penile
urethral stenosis, and in females causes a rectovaginal fistula.
Imperforate anus occurs when the anal membrane does not rupture. Anal
stenosis occurs if it partially ruptures.
Other types of abnormalities include low and high defects. Low defects
include problems with the protocdeum and anal membrane. Imperf. anus in
an example, as in anal agenesis, in which there is no the anus. If a
fistula is present, it empties into the urethra, while if there is no
fistula the rectum ends blindly. The anus can also be covered by
genital folds in what is known as “covered anus”.
High anorectal defects – in anorectal agenesis, there is no rectum,
anal canal, or anus, and fistulas form into the urethra or vagina. Main
difference with rectal defects is that there is no anus whatsoever. In
rectal atresia, lack of blood supply causes the rectum to end. However,
you still have an anus. In persistent cloaca, the bladder, vagina, and
rectum form one cavity.
Hirschsprung’s disease is caused by lack of migration of neural crest
cells into the colon. Above a certain point, peristalsis occurs, but
below that point there is an stenosis that causes a backup of flow,
causing the megacolon. The distal aganlionic bowel is narrowed.

Genital Development Questions
Where do the primordial germ cells come from?
Primordial germ cells come from the epiblast, then migrate to the
extraembryonic yolk sac where they remain for 5 weeks. They then
migrate through the dorsal mesentery to the posterior body wall next to
T10. They are drawn by chemotrophic agents.
The coelemic tissue is stimulated by the germ cells to differentiate
into the primary sex cords, which gives rise to the genital ridge.
Lateral to the genital ridge, the paramesonephrics ducts develop,
meeting with the mesonephric ducts inferiorly. In the male, the primary
sex cords first give rise to the Sertoli cells, as a result of
expression of the SRY gene. These Sertoli cells join with the
primordial germ cells to develop into the testis cords. Leydig cells
line between the testis cords and secrete testosterone. The Sertoli
cells secrete MIF, which causes the degeneration of the paramesonephric
duct in males. These testis cords will not become seminiferous tubules

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until puberty, when high levels of testosterone cause their
differentiation.
In the female, the primary sex cords degenerate, and are replaced by
the secondary sex cords, which arise from the coelemic epithelium. They
surround the primordial germ cells, eventually becoming the follicular
cells while the germ cells become oocytes. The secondary sex cords are
also called the cortical sex cords, which should give some idea as to
what their function is (think of the cortical granules).
The function of the SRY gene is to induce the expression of other sexdetermining genes, the most important of which is TDF, or testis
determinging factor. So again, SRY leads to the expression of TDF,
which in turn induces other genes such as SOX-9. SRY causes all the
changes responsible for becoming male – if it deleted, female is the
default phenotype.
The mesonephric duct leads to the creation of the vas deferens in males
(it acquires a layer of smooth muscle), while in the female the
mesonephric ducts become the paroophoron and epoophoron.
The paramesonephric duct becomes the ovary, uterus, cervix, and upper
part of the vagina in the female. The distal part of the
paramesonephric ducts fuse together in the midline near the
paramesonephric tubercle, an outgrowth of ectoderm. The paramesonephric
tubercle leads to the sinovaginal bulbs, which create the vagina. The
hymen is a barrier between the vagina and UG sinus. In the male, the
paramesonephric ducts become the utricle of the prostate and the
appendix of the testis. It degenerates in males due to the effects of
MIF.
The uterus is formed from the fusion of the paramesophric ducts. The
vagina is formed from the vaginal plate, which is formed from the
vaginal bulbs. If the ducts don’t fuse properly, a bihorned uterus, or
even a double uterus can occur. If the vaginal bulbs don’t fuse, you
get a double vagina, or no vagina if the vaginal bulbs don’t develop.
The labioscrotal folds form the labia majora in the female, and the
scrotum in the male. The folds fuse in the male due to the presence of
DHT, which is converted from testosterone by 5-alpha-reductase. DHT
also causes the formation of the prostate and the elongation of the
phallus, including the fusion of the urethral folds to form the penile
urethra.
The penile urethra is derived from endoderm, with the exception of the
fossa navicularis, an ingrowth of ectoderm. It is formed by the fusion
of urethral folds and canalization of the urethral plate.
The prostate is formed from the urethra, induced by DHT. It is an
endodermal outgrowth.
Ø Derivatives of the prosencephalon, mesencephalon, and rhombencephalon
What are the derivatives of answer?
- Ans. procen.........telen cephalon,dien
- mesen..........mesencephalon
- rhomben........metenand, myelencephalon
- telen......cerebral.h,basalganglia

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dien.......thalamus and hypothalamus
mesen.........midbrain
meten........pons,cerebellum
myelen...........medulla
Ø Derivatives of the first to fourth POUCHES
What happens if no third and fourth pouch?
- Ans. 1 => epithelial lining of auditory and middle ear cavity
- 2 => lining of palatine tonsil crypts
3 => inf. parathyroid gland, thymus
4 => sup.parathyroid gland
absence of 3rd and 4th then no THYMUS AND PARATHYROID, so DiGeorge's
Syndrome.
Ø Derivatives of the first, second, third, fourth, and sixth arches? If
anyone has a mnemonic for this one that would be great!
- Ans. Each Arch (mesoderm) is associated with a nerve, (from ectoderm
that grows into the arch) gives rise to either arteries, muscles or
both, and is also associated with a skeletal structure (from neural
crest)...
- ARCH 1 (all M's)
nerve: mandibular (V-3)
artery: none
muscle: muscles of mastication and tensor tympani
skeletal malleus (and incus) maxilla and mandible
- ARCH 2: (all S's)
nerve: seven (VII)
artery: none
muscle: stapedius, stylohyoid, and seven's muscles (facial expression)
skel: leSSer horn and upper body of hyoid
- ARCH 3: (3=2+1: 2 types of arteries, and 1 muscle)
also: 3x3=9: nerve is CN IX)
nerve: XI
arteries: r and l CC, r and l Internal carotid
muscle: stylopharangeus
skel: greater horn and lower body of hyoid
- ARCH 4 and 6: (nerve is 6+4= 10)
- ARCH 4:
nerve: X and superior laryngeal
artery: r subclavian and arch of aorta
muscle: cricothyroid
skel: thyroid cart
- ARCH 6:
nerve: X and recurrent laryngeal
artery: R and L Pulm arteries, and Ductus Art.
muscle intrinsic muscles of crycothyroid
skel: all other laryngeal cart.
Ø Derivatives of the first groove?
other grooves?
What happens if second, third and fourth grooves persist?
- Ans. 1....lining of ext.auditory meatus
if persisits leads to pharyngeal cysts
- first groove, and rest move! (only the first one persists and
develops into the lining of the EAM) if the other ones do, that leads
to branchial cyst and lateral cervical cyst)

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Ø Are the following made from endo, meso or ectoderm?
grooves?
arches?
pouches?
- Ans. arches...mesoderm
grooves....ecto
pouches....endo
- way to remember...
GAP
from out to in:
ecto, meso, endo
Ø What does the left horn of the sinus venosus develop into? what about
the right horn?
- Ans. left...coronary sinus
rt...smooth part of rt atrium
Ø What cranial nerve is associated with pharyngeal pouches I, II, III,
IV, and VI?
I - V-3
II - VII
III - IX
IV - X
VI - X
Ø Where does the foregut, midgut and hindgut end?
- Ans. Foregut - upper duodenum
midgut - proximal 2/3 of transverse colon
hingut - upper part of anal canal
Ø What is the adult structure found in the embryo as:
left umb. vein?
ductus venosus?
ductus arteriosus?
umb. artery?
- Ans. left umbilical v. - lig. teres
ductus ven. - lig. venosum
ductus arteriosus - lig. arteriosum
umbil. art. - medial umbilical ligaments
Ø When does the septum primum and septum secundum fuse? before or after
birth? and what happens if it does not?\
- Ans. foramen ovale is b/w septum primum and separates secundum. FO
fuses after birth, otherwise - left-to-right shunt (ASD?)
Ø What are the 5 derivatives of the ventral mesentery?
- Ans. Lesser omentum- Hepatoduodenal ,Hepatogastric ligament
- plus falciform lig.,coronary lig., triangular lig.
- Right... all the liver ligaments are from ventral mesentery
(falciform, hepatoduodenal, hepatogastric, coronary, and triangular)
All others (gastro-, spleno-, SI, LI, and colon) are derived from
Dorsal mesentery
Ø What three things cause the indifferent gonad to become a testis? and
where do they come from?
- Ans. Testostrone by Leydig
MIF: by Sertoli and finally the main TDF on Y chromosome (short arm)

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Ø What are the arteries of the foregut, midgut and hindgut?
What is the only organ supplied by the foregut artery, that is of
mesodermal origin?
- Ans. celiac, superior mesenteric, inferior mesenteric.
- Spleen is a mesodermal organ and gets blood supply from celiac artery
Ø What structure is derived from the prechordal plate?
- Ans. MOUTH.

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