Professional Documents
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External oblique *
Internal oblique *
• ORIGIN: Lumbar fascia, anterior 2/3 of iliac crest and lateral 2/3 of
inguinal ligament
Transversus abdominis *
Rectus abdominis *
Pyramidalis *
• ORIGIN: Anterior surface of pubis
• INSERTION: Linea alba
NERVES
• External oblique, internal oblique and transversus: Lower 6 thoracic
nerves and L1 (ileoinguinal and ileohypogastric nerves)
• Pyramidalis: T12 *
1
FUNCTION
• Note that the aponeurosis of the internal oblique splits to enclose the
rectus abdominis
• Arcuate line *: Site where the aponeuroses of the posterior wall pass
anterior to the rectus at the level of the anterior superior iliac spine. The
inferior epigastric artery enters the rectus sheath at this point and lies
posterior to the rectus abdominis. Pyramidalis lies within the rectus
sheath.
2
ILIACUS
QUADRATUS LUMBORUM
• The linea alba is split to separate the recti abdominis which are NOT
cut
3
AORTIC ARCH
• Runs upwards, backwards and to the left, initially anterior then to the
left of the trachea
Branches
• Brachiocephalic artery which divides into the right common carotid and
right subclavian arteries
• Left common carotid artery
• Left subclavian artery
Branches
1
• Gives off two anterior intercostal arteries to the upper 6 intercostal
spaces
• Pericardiophrenic artery to the pericardium
• Mediastinal arteries to the anterior mediastinum including the thymus
• Perforating arteries to thoracic and anterior abdominal wall
• The internal thoracic vein drains into the brachiocephalic vein
• Formed from the left and right brachioceplalic veins (which are formed
from the subclavian and internal jugular veins)
• Receives the azygos vein just before piercing the pericardium
• Lies anterior to the trachea and aorta in the superior mediastinum
Lymph from the right side of the head and neck, right upper limb and right side of the
thorax is drained by the right jugular, subclavian and bronchomediastinal trunks
respectively. These may unite to form the right thoracic duct which drains into the
right brachiocephalic vein or drain independently in to the vain.
2
TRUE PELVIS
• That part of the pelvis between the pelvic inlet and the pelvic outlet
• The pelvic inlet is oval in shape in the Gynaecoid pelvis and has the
following borders:
1) Posterior: Coccyx *
2) Lateral: Ischial tuberosities *
3) Anterior: Pubic arch formed by the simphysis pubis and the ischio-pubic
rami *
• 5 rudimentary vertebrae
• The anterior and upper margin of the first sacral vertebra bulges
forward as the posterior margin of the pelvic inlet and forms the sacral
promontory *
• Articulates with innominate bone at the sacro-iliac joint, with the 5th
lumbar vertebra superiorly (where it is tilted forwards at the lumbo-
sacral angle) and with the coccyx inferiorly
• The laminae of S5 and occasionally S4 fail to fuse in the mid-line,
forming the sacral hiatus
1
• The vertebral foramina form the sacral canal which contains the
cauda equine, filum terminale and meninges as far as the lower border
of S2 while the rest of the canal contains the filum terminale and lower
sacral and coccygeal nerves *
• The anterior / posterior surfaces contain 4 foramina for the anterior
and posterior rami of the upper 4 sacral nerves respectively *
• The piriformis muscle arises from the front of the lateral mass of the
sacrum and leaves the pelvis through the greater sciatic foramen to
insert onto the greater trochanter *
• Less massive
• The anterior iliac spines more widely separated - greater lateral
prominence of the hips.
• Wider pelvic inlet - both antero-posterior and transverse diameters
• Pelvic inlet more circular
• More shallow
• The sacrum is shorter wider, and its upper part is less curved
2
3
EXTERNAL GENITALIA
• Labia minora: hairless folds of skin within the labia majora; unite
posteriorly to form the fourchette; split anteriorly to enclose the clitoris,
forming an anterior prepuce and a posterior frenulum
UPPER HALF
1
• Derived from hind-gut endoderm *
• Lined by columnar epithelium *
• Thrown into vertical folds called anal columns *
• Autonomic supply from the inferior hypogastric plexus, sensitive to
stretch only *
LOWER HALF
Internal
External
2
• Skeletal muscle *
• Sub-cutaneous part - lower half of anal canal, no bony attachments *
• Superficial part - attached to the perineal body anteriorly and the
anococcygeal body posteriorly *
• Deep part - no bony attachments, blends with puborectalis *
3
INGUINAL LIGAMENT *****
1
• THE ILIOINGUINAL NERVE ENTERS THE THIGH THROUGH THE
SUPERFICIAL INGUINAL RING. *
• VAS DEFERENS
• TESTICULAR VESSELS
• LYMPHATICS
• LYMPHATICS
2
SCROTUM *****
• MADE UP OF FOLLOWING LAYERS (SUPERFICIAL - DEEP):
• SKIN
• DARTOS MUSCLE - SMOOTH MUSCLE, CONTINUOUS WITH FATTY /
MEMBRANEOUS LAYER OF SUPERFICIAL FASCIA OF ANTERIOR
ABDOMINAL WALL; INNERVATED BY SYMPATHETIC FIBRES AND
RESPONSIBLE FOR WRINKLING OF OVERLYING SKIN
3
4
CECUM *****
APPENDIX *****
• 8-13cm long
• Lies in RIF with its base located 1/3 of the way up the line
joining the anterior superior iliac spine to the umbilicus
(McBurney’s point)
1
ASCENDING COLON *****
• retro-peritoneal
• 38cm long, from the right colic flexure to the left colic flexure,
which is attached to the diaphragm by the phrenico-colic ligament
2
• Nerves - proximal 2/3 - superior mesenteric plexus (vagus -
parasympathetic); distal 1/3 - inferior mesenteric plexus
(sympathetic) and pelvic splanchnic nerves (parasympathetic)
• NOTE that the junction between the proximal 2/3 and distal 1/3
of the transverse colon is the junction between the mid-gut and
the hind-gut, hence the arrangement of blood, nerve supply and
lymphatics.
3
4
LIVER *****
• The falciform ligament divides the liver into right and left
lobes and splits on the superior surface of the liver, the right
layer forming the upper layer of the coronary ligament while
the left layer forms the upper layer of the left triangular
ligament
1
The porta hepatis contains the following structures *****
• The common hepatic duct is formed from the left and right
hepatic ducts
• The cystic duct runs from the gall bladder to join the RIGHT
side of the common hepatic duct, forming the common bile
duct
• The common bile duct is located in the right free edge of the
lesser omentum, anterior to the epiploic foramen, in front of
the portal vein and to the right of the hepatic artery
• The common bile duct then runs behind the first part of the
duodenum (to the right of the gastro-duodenal artery) then
behind the head of the pancreas to open half way down the
second part of the duodenum into the ampulla of Varter
2
GALL BLADDER *****
• The fundus is at the level of the tip of the 9th right costal
cartilage
3
THE PLEURA
THE LUNGS
1
2
PYRIFORMIS
1
COCCYGEUS
2
THE VAGUS NERVES *****
Right
Left
• Enters the thorax between the left common carotid and left
subclavian arteries
Branches
• The left vagus gives off the left recurrent laryngeal nerve at
the level of the ligamentum arteriosum. The nerve hooks
around the ligament to ascend between the trachea and the
oesophagus on the left side and supplies all the muscles of
the left vocal cord except the cricothyroid muscle (external
laryngeal branch of the vagus)
1
THE PHRENIC NERVES *****
Right
Left
• Enters the thorax on the left side of the left subclavian artery
• Crosses the left side of the aortic arch and the left vagus
nerve
2
• Gives grey rami communicantes to the thoracic spinal
nerves
3
THE LUMBAR PLEXUS
• Branches emerge from the lateral and medial borders and the
anterior surface of psoas major
LATERAL BRANCHES
MEDIAL BRANCHES
ANTERIOR BRANCH
1
• Made up of 4 segmentally arranged ganglia; the upper two
ganglia receive white ramus communicans from the 1st and 2nd
lumbar nerves
2
SACRAL PLEXUS *****
Branches
• Nerve to piriformis
1
PELVIC SYMPATHETIC TRUNK *****
HYPOGASTRIC PLEXUSES
2
PELVIC SPLANCHNIC NERVES *****
3
• Parasympathetic supply to the ovary is from the vagus
nerve. Sympathetic innervation is from the L1/2 segment *
4
PUDENDAL NERVE *****
• Lies medial to the internal pudendal artery as it exits from the pelvis
into the perineum *
Branches
• Leaves the pelvis through the greater sciatic foramen, and emerges
between the Piriformis and Coccygeus *
• Crosses the ischial spine, and enters the perineum through the lesser
sciatic foramen. *
• Then crosses the Obturator internus, along the lateral wall of the
ischiorectal fossa, ~ 4 cm above the lower margin of the ischial
tuberosity. *
• Passes forward between the two layers of the fascia of the urogenital
diaphragm
• Runs forward along the medial margin of the inferior ramus of the pubis
behind the pubic arcuate ligament *
• Branches include the inferior rectal artery (supplies lower half of anal
canal) and branches to the penis or labia and clitoris *
1
SUPERFICIAL PERINEAL POUCH
• Contains the structures forming the root of the clitoris: the bulb of the
vestibule, bulbospongiosus and ischiocavernosus muscles; superficial
transverse perineal muscle with their nerve supply (perineal branch of
the pudendal nerve), blood supply (branches of the internal pudendal
artery) and the perineal body
BULBOSPONGIOSUS MUSCLE *
2
ISCHIOCAVERNOSUS MUSCLE *
• The two layers fuse anteriorly, leaving a gap beneath the simphysis
pubis
• The enclosed space between the two fascial is the deep perineal
pouch
Contains:
3
MUSCLES OF THE DEEP PERINEAL POUCH
• Has a root made up of three masses of erectile tissue ? the bulb of the
vestibule (divided into two by the vaginal orifice) and the left and right
crura
• The crura are covered by the ischiocavernosus muscles and form the
corpora cavernosa anteriorly
4
PERITONEUM *****
LESSER OMENTUM
• Runs from the lesser curvature of the stomach to the porta hepatis
• Its right free border forms the ANTERIOR margin of the opening
into the lesser sac (epiploic foramen) and contains the RIGHT gastric
artery
1
Boundaries of the epiploic foramen *****
PARACOLIC GUTTERS
• The right lateral extends from the pelvis to the right posterior sub-
phrenic space *
• The right medial is closed off from the pelvis by the mesentry of the
small intestine *
2
THE OVARY *****
• Venous drainage - LEFT -left ovarian vein drains into left renal
artery; RIGHT - right ovarian vein drains into inferior vena cava *
1
FALLOPIAN TUBES *****
2
THE UTERUS *****
• Lymph: *
1)Fundus - accompany ovarian artery to para-aortic nodes at the level of L1
3
• Ascends within the broad ligament on the lateral aspect of the
uterus
• Gives off descending branch to the cervix and vagina *
LIGAMENTS *****
The uterus is supported mainly by the tone of the pelvic floor muscles (levator
ani) which are partly inserted onto the perineal body and condensations of
pelvic fascia forming the transverse cervical, pubo-cervical and utero-sacral
ligaments.
4
CERVIX *****
• Approximately half its length is visible in the vagina (vaginal cervix), the
rest being above the vagina (supra-vaginal cervix) *
• The vaginal cervix ~3 cm long and 2.5 cm wide. Size and shape varies
widely with age, hormonal state, and parity - bulkier and the external
with a wider and more slit-like external os in multiparous women.
• The uterine arteries reach the margins of the cervix within the
parametrium *
• The vaginal cervix projects free into the anterior wall of the vagina
between the anterior and posterior fornices.
5
Blood supply *****
• Cervical and vaginal branches supply the cervix and upper vagina.
Lymphatics *****
Regional lymph nodes for the cervix include: paracervical, parametrial, presacral,
sacral, external iliac, common iliac, hypogastric (obturator), internal iliac..
• The uterosacral ligaments are the conduits of the main nerve supplying
to the cervix, derived from the hypogastric plexus.
6
THE VAGINA *****
Relations *****
7
VAGINAL SUPPORT *****
8
THE RIGHT KIDNEY *****
• Lower level than the left due to the bulk of the right lobe of the liver
• 25cm long, leaves renal pelvis behind the renal vein and descends on
psoas major which separates it from the tips of the transverse
processes of the lumbar vertebrae *
• Enters the pelvis in front of the sacro-iliac joint and the bifurcation of
the common iliac artery *
1
• Supplied by the renal, testicular / ovarian and superior vesical
arteries *
• Within the pelvis, the ureter runs at first downward on the lateral wall
of the pelvic cavity, along the anterior border of the greater sciatic
notch and under cover of the peritoneum. *
• It lies in front of the internal iliac artery and medial to the obturator
nerve obturator, inferior vesical, and middle rectal arteries *
• In the female, the ureter forms the posterior boundary of the ovarian
fossa,in which the ovary is situated and is separated from the ovary by
pelvic peritoneum *
• In the region of the ischial spine, it runs medially and forward beneath
the base of the broad ligament on the lateral aspect of the cervix and
upper part of the vagina to reach the bladder. *
• At the bladder base, the ureters are ~5 cm apart in the full bladder
and 2.5cm apart when the bladder is empty. The ureter lies anterior to
the anterior vaginal fornix as it reaches the bladder *
• Finally, the ureters run obliquely for about 2 cm. through the wall of
the bladder and open by slit-like apertures into the cavity of the viscus
at the lateral angles of the trigone. *
2
During pelvic surgery, the ureters can be injured at the following
points:*****
RIGHT URETER *
LEFT URETER *
Structure *****
• The fibrous coat is continuous with the renal capsule and the fibrous
structure of the bladder
3
SUPRARENAL GLANDS *****
• Right related anteriorly to: right lobe of liver and lateral border of
inferior vena cava *
• Single suprarenal vein drains into renal vein on the left or inferior
vena cava on the right *
4
THORAX - SURFACE ANATOMY
THE RIB
1
FIRST RIB
INTERCOSTAL MUSCLES
2
INTERCOSTAL VESSELS
3
Branches *****
4
SIGMOID COLON *****
• ~13cm long
• Upper third - covered by peritoneum on its anterior and
lateral surfaces, middle third covered by peritoneum on the
anterior surface only and lower third devoid of peritoneum *
1
Blood supply: *****
2) Middle rectal artery - branch of internal iliac artery - muscular coat mainly
2
STOMACH *****
Anterior
Posterior
1
• Left / right gastric veins - drain into portal vein directly
DUODENUM *****
2
• Posterior: Hilus of right kidney and right ureter *
• Inferior: Jejunum
• Anterior: Jejunum
3
SURFACE ANATOMY - ABDOMEN *****
ii) The inter-tubercular plane - joins tubercles of iliac crests (level L5)
Trans-pyloric plane:
Abdominal wall
Dermatomes *****
• Xiphoid process - T7
• Umbilicus - T10
• Pubis - L1
1
Venous drainage: *****
• Few para-umbilical veins drain into the portal vein via the
ligamentun teres, forming a portal-systemic anastomosis.
Distended veins may indicate portal hypertension *
Lymphatics: *****
HERNIAS
INGUINAL
• The sac of all inguinal hernias lies above and medial to the
pubic tubercle
2
FEMORAL
UMBILICAL
• Congenital - exomphalos
EPIGASTRIC
RICHCTER’S
3
THE DIAPHRAGM *****
Three origins:
Action
OPENINGS *****
• Aortic - anterior to T12 between the crura, transmit the aorta, thoracic
duct and azygos vein *
• Oesophageal - level of T10, also transmits right and left vagi,
oesophageal branch of the left gastric vessels and lymphatics from the
lower third of the oesophagus *
• Caval - level of T8 in the central tendon, also transmits terminal
branch of the right phrenic nerve *
• The superior epigastric vessels pass between the sternal and costal
origins ; the left phrenic nerve pierces the left dome; the greater, lesser
and lowest splanchnic nerves pierce the crura and the sympathetic
trunk lies posterior to the medial arcuate ligament. *
1
2
THE RIGHT ATRIUM
• Lies posterior to the right atrium and forms the base of the
heart. Separated from the oesophagus by the pericardium
1
CONDUCTING SYSTEM OF THE HEART *****
Sino-atrial node *
• Pacemaker
Atrio-ventricular node *
Atrio-ventricular bundle
2
BLOOD SUPPLY TO THE HEART *****
Venous drainage
• The anterior cardiac vein drains directly into the right atrium
3
THE MEDIASTINUM
TRACHEA
• Left side: arch of the aorta with left common carotid and
subclavian arteries, left vagus and left phrenic nerves.
1
MAIN BRONCHI
RIGHT
• Gives off the superior lobar bronchus before entering the hilum of
the lung where it divides into the middle and inferior lobe bronchus
LEFT
• At the hilum of the left lung divides into superior and inferior lobe
bronchi
2
THE OESOPHAGUS
•Left side: left subclavian artery, aortic arch, thoracic duct and
mediastinal pleura
Blood supply
Lymphatic drainage
•Level T10
1
2
THE PANCREAS *****
• Head, neck, body and tail. The uncinate process of the head lies
posterior to the superior mesenteric vessels. The neck lies anterior to
the origin of the superior mesenteric artery and portal vein
• Related posteriorly to the bile duct, portal vein, splenic vein, inferior
vena cava and aorta, origin of superior mesenteric artery, left psoas,
left suprarenal gland, left kidney and hilus of spleen
• The splenic artery runs along the upper border of the pancreas
• Drained by main pancreatic duct, opening half way down the second
part of the duodenum. The accessory pancreatic duct, where present,
opens above the opening of the main duct
SPLEEN *****
• Lies in the left hypochondrium under the 9th, 10th and 11th ribs with
its long axis along the shaft of the 10th rib. Extends to the mid-axillary
line and the normal spleen is not palpable. It is intra-peritoneal *
1
2
THE URINARY BLADDER *****
1
PHARMACOLOGY *****
2
3
Question 1: With respect to the scrotum and its contents
1
Question 4: Prolactin
2
Question 7: With respect to the scrotum and its contents
a. The rectus abdominis originates from symphysis pubis and the pubic
crest
True False
b. The rectus abdominis inserts onto the 5th, 6th and 7th costal cartilages
and the xiphoid process (T)pyramidalis lies deep to rectus abdominis
True False
c. The external oblique, internal oblique and transversus abdominis are
supplied by the lower 6 thoracic nerves and the ileoinguinal and
ileohypogastric nerves
True False
d. Pyramidalis is supplied by L1
True False
3
a. Is formed by the aponeurosis of the internal oblique muscle
True False
b. Is attached laterally to the anterior superior iliac spine
True False
c. Is attached medially to the posterior superior iliac spine
True False
d. Forms the posterior wall of the inguinal canal
True False
a. Ilioingiunal nerve
True False
b. Femoral artery
True False
c. Femoral branch of the genitor-femoral nerve
True False
d. Lateral cutaneous nerve of the thigh
True False
Question 13: With respect to the blood supply and lymphatic drainage of
the skin of the anterior abdominal wall
4
a. The superior epigastric artery is a branch of the aorta
True False
b. The inferior epigastric artery is a branch of the external iliac artery
True False
c. The lateral aspects of the abdominal wall are supplied by the lumbar
arteries and the deep circumflex iliac artery
True False
d. There is no connection between the veins of the anterior abdominal
wall and the portal vein
True False
Question 14: The following structures are present within the inguinal
canal in the male
a. Testicular artery
True False
b. Vas derefens
True False
c. Inguinal nerve
True False
d. Genital branch of the genitor-femoral nerve
True False
a. The pubic crest forms the base of the superficial inguinal ring
True False
b. The margins of the superficial inguinal ring form the external spermatic
fascia
True False
c. The anterior wall is formed by the aponeurosis of the external oblique
muscle
True False
d. The anterior wall is reinforced laterally by the origin of the internal
oblique muscle
True False
5
Question 1: With respect to the lumbar plexus
True False
b. The femoral nerve enters the thigh anterior to the inguinal ligament
True False
c. The femoral nerve enters the thigh lateral to the femoral sheath
True False
d. The femoral nerve enters the thigh medial to the femoral canal
True False
True False
b. Lies to the right of the cisterna chyli
True False
c. Bifurcates into the left and right common iliac arteries at the level of the first lumbar vertebra
True False
d. Lies to the left of the inferior vena cava
True False
True False
b. Lies anterior to the first part of the duodenum
True False
c. Lies within the lesser omentum
True False
d. Lies posterior to the opening into the lesser sac
True False
a. The lumbar plexus is formed from the posterior rami of the upper 4 lumbar nerves
True False
b. The nerves of the lumbar plexus receive grey rami communicantes from the sympathetic trunk
True False
c. The upper 3 lumbar nerves give off white rami communicantes to the sympathetic trunk
True False
d. The lumbar plexus is formed anterior to the psoas and iliacus muscles
True False
Question 5: With respect to the blood supply to the gastro-intestinal tract
True False
b. The middle colic artery is a branch of the inferior mesenteric artery
True False
c. The ileocolic artery is a branch of the superior mesenteric artery
True False
d. The inferior mesenteric artery is the artery to the hind-gut
True False
a. e) The upper two sympathetic ganglia receive a white ramus communicans from the first and
second lumbar nerves
True False
b. f) Gives off grey rami communicantes to the lumbar spinal nerves
True False
c. g) The left sympathetic trunk is posterior to the inferior vena cava
True False
d. h) Enters the abdomen behind the medial arcuate ligament
True False
True False
b. The celiac artery supplies the lower third of the oesophagus to the duodeno-jejunal junction
(ligament of Treitz)
True False
c. The inferior mesenteric artery is the artery to the mid-gut
True False
d. The superior mesenteric artery supplies the distal half of the second part of the duodenum to
the junction between the proximal 2/3 and distal 1/3 of the transverse colon
True False
True False
b. Lies posterior to the opening into the lesser sac
True False
c. Lies to the right of the bile duct
True False
d. Lies posterior to the portal vein
True False
True False
b. Receives the greater and lesser splanchnic nerves
True False
c. Receives parasympathetic post-ganglionic fibres from the vagus nerve
True False
d. Supplies the proximal 2/3 of the transverse colon
True False
Question 10: With respect to the blood supply to the gastro-intestinal tract
True False
b. The superior rectal artery is a continuation of the inferior mesenteric artery
True False
c. The splenic artery is a branch of the celiac artery
True False
d. The short gastric arteries are branches of the splenic artery
True False
True False
b. The genito-femoral nerve emerges from the lumbar plexus on the anterior surface of psoas
major
True False
c. The genital bramch of the genito-femoral nerve enters the spermatic cord
True False
d. The femoral branch of the genito-femoral nerve supplies the cremaster muscle
True False
True False
b. Pierces the central tendon of the diaphragm at the level of T12
True False
c. Lies medial to the right ureter
True False
d. Is related anteriorly to the opening into the lesser sac
True False
True False
b. Lies anterior to the lesser sac
True False
c. Is a branch of the abdominal aorta at the level of the 12th thoracic vertebra
True False
d. Has three branches ? the right gastric artery, the splenic artery and the hepatic artery
True False
True False
b. The obturator nerve emerges from the lumbar plexus on the medial border of psoas major
True False
c. The obturator nerve crosses the pelvic brim infront of the sacral promontory
True False
d. The obturator nerve crosses the pelvic brim anterior to the common iliac vessels
True False
True False
b. Lies to the left of the cysterna chyli
True False
c. Is related posteriorly to the pancreas
True False
d. Originates behind the left common iliac vein
True False
Question 1: With respect to the bladder and urodynamic studies
1
Question 4: With respect to the uterus
2
Question 7: The sigmoid colon
a. Is retro-peritoneal
True False
b. Is continuous with the rectum at the level of S3
True False
c. Is continuous with the descending colon in front of the right external
iliac artery
True False
d. Is related anteriorly to the uterus
True False
3
Question 10: With respect to the uterus
a. The fundus is that part of the uterus above the entrance of the fallopian
tubes
True False
b. The uterus is 8cm long x 2cm wide by 5cm thick
True False
c. In saggital section, the cavity of the uterus is triangular in shape
True False
d. In coronal section, the cavity of the uterus is represented by a cleft
True False
a. Perineal body
True False
b. Transverse cervical ligament
True False
c. Utero-sacral ligament
True False
d. Pubo-cervical ligament
True False
a. The cervix
True False
b. The bladder
True False
c. The appendix
True False
d. The perineal body
True False
4
Question 13: The ovary
5
Question 1: The pelvic splanchnic nerves
1
Question 4: The levator ani muscle
2
Question 7: The obturator nerve
3
Question 10: The levator ani muscle
4
a. Join the inferior hypogastric plexus directly
True False
b. Join the superior hypogastric plexus directly
True False
c. Provide parasympathetic supply to the hind-gut
True False
d. Provide sympathetic supply to the bladder
True False
5
Question 1: The external anal sphincter
1
Question 4: The superficial perineal pouch in the female
2
Question 7: The superficial perineal pouch in the female
a. Is 2cm long
True False
b. Has its axis directed downwards and forwards from the rectal ampulla
True False
c. Has its anterior and posterior walls in apposition by the tone of the
levator ani muscles
True False
d. Is related posteriorly to the anococcygeal body
True False
3
Question 10: The ischiocavernosus muscle
4
Question 13: The ischio-rectal fossa
5
Question 1: The pulmonary trunk
a. Is formed from the right brachiocephalic and left internal jugular veins
True False
b. Receives blood from the azygos vein
True False
c. Lies anterior to the aorta in the superior mediastinum
True False
d. Lies posterior to the trachea in the superior mediastinum
True False
1
Question 4: The trachea
2
Question 7: The arch of the aorta has the following branches
3
Question 10: Within the mediastinum
4
a. Communicates with the pulmonary vein
True False
b. Has papillary muscles
True False
c. Is traversed by the moderator band
True False
d. Has papillary muscles which are connected to the cusps of the
tricuapid valve by the chordae tendinae
True False
5
Question 1: The diaphragm
1
Question 4: The internal thoracic artery
2
Question 7: The diaphragm
Question 10: With respect to the lymphatic drainage of the thoracic wall
3
a. Lymphatic drainage of the skin of the anterior chest wall is to the
anterior axillary nodes
True False
b. Lymphatic drainage of the skin of the posterior chest wall is to the
posterior axillary nodes
True False
c. Lymphatic drainage of the anterior part of the intercostal spaces is to
the internal thoracic nodes
True False
d. Lymphatic drainage of the posterior part of the intercostal spaces is to
the para-aortic nodes
True False
a. Has the scalenus anterior muscle inserted onto the scalene tubercle
True False
b. Is crossed by the brachial plexus anterior to the scalenus anterior
muscle
True False
c. Articulates with the transverse process of the 7th cervical vertebra
True False
d. Is palpable throughout its length
True False
4
a. Has a central muscular part and a peripheral tendinous part
True False
b. Has a sternal origin from the posterior surface of the body of the
sternum
True False
c. Has a costal origin from the deep surfaces of the lower 4 ribs and their
costal cartilages
True False
d. Has a right crus originating from the medial arcuate ligament
True False
a. The xiphisternal joint lies opposite the body of the 9th thoracic vertebra
True False
b. The lowest part of the costal margin is formed by the 12th rib
True False
c. The lowest part of the costal margin lies at the level of the 3rd lumbar
vertebra
True False
d. The first rib is palpable throughout its length
True False
5
Question 1: The ascending colon
True False
b. Is related superiorly to the right lobe of the liver
True False
c. Is related anteriorly to the greater omentum
True False
d. Has parasympathetic supply from the vagus nerve via the inferior mesenteric plexus
True False
True False
b. The interlobular ducts are located at the centre of the hepatic lobule
True False
c. The right hepatic duct drains bile from the caudate lobe of the liver
True False
d. The left hepatic duct drains bile from the quadrate lobe of the liver
True False
True False
b. Is related posteriorly to the psoas and iliacus muscles
True False
c. Is related posteriorly to the femoral nerve
True False
d. Is related posteriorly to the lateral cutaneous nerve of the thigh
True False
True False
b. Crosses superior to the uterine artery in the broad ligament
True False
c. Is supplied by the uterine artery within the pelvis
True False
d. Lies more than 5cm lateral to the supra-vaginal cervix
True False
1
a. Is 25cm long
True False
b. Is retro-peritoneal throughout its length
True False
c. The first part is 5cm long and lies on the intercristal plane
True False
d. The first part is related anteriorly to the quadrate lobe of the liver and the gall bladder
True False
True False
b. Lies anterior to the lesser sac
True False
c. Is posterior to the stomach
True False
d. Is related posteriorly to the splenic vein
True False
True False
b. Receives its blood supply from the inferior mesenteric artery
True False
c. Receives its blood supply from branches of the ileocolic artery
True False
d. Is supplied by the left and right caecal arteries
True False
a. Enters the pelvis posterior to the bifurcation of the common iliac artery
True False
b. Enters the pelvis in front of the sacro-iliac joint
True False
c. Is supplied by the renal artery
True False
d. Is supplied by the testicular / ovarian artery
True False
2
a. The lobar arteries supply the renal pyramids
True False
b. The interlobular arteries arise from the lobar arteries
True False
c. The efferent glomerular arteriols arise from the interlobular arteries
True False
d. The renal vein drains directly into the inferior vena cava
True False
a. Is 35cm long
True False
b. Leaves the renal pelvis anterior to the renal vein
True False
c. Is adherent to visceral peritoneum
True False
d. Is separated from the tips of the transverse processes of the lumbar vertebrae by psoas major
True False
a. Parasympathetic supply to the proximal 2/3 is from the vagus via the inferior mesenteric
plexus
True False
b. Parasympathetic supply to the distal 1/3 is from pelvic splanchnic nerves
True False
c. Sympathetic supply to the proximal 2/3 is from the superior mesenteric plexus
True False
d. Sympathetic supply to the distal 1/3 is from the inferior mesenteric plexus
True False
a. Is supplied by the left colic artery, a branch of the inferior mesenteric artery
True False
b. Lymphatic drainage is to the inferior mesenteric nodes
True False
c. Receives sympathetic supply from the pelvic splanchnic nerves
True False
d. Receives parasympathetic supply from the pelvic splanchnic nerves
True False
Question 13: With respect to the nerve supply and lymphatic drainage of the stomach
3
a. The lymphatics drain into the superior mesenteric nodes
True False
b. The anterior vagal trunk is derived mainly from the left vagus nerve
True False
c. The posterior vagal trunk supplies the pancreas
True False
d. The posterior vagal trunk supplies the intestine as far as the splenic flexure
True False
True False
b. Is intra-peritoneal
True False
c. Has the transverse mesocolon attached to its inferior border
True False
d. Has the anterior layer of the greater omentum attached to its inferior border
True False
Question 15: The following structures are present at the porta hepatis
True False
b. Right and left branches of the hepatic artery
True False
c. Right and left branches of the hepatic vein
True False
d. The upper part of the free edge of the lesser omentum
True False
4
Question 1: With respect to the scrotum and its contents
1
Question 4: Prolactin
2
Question 7: With respect to the scrotum and its contents
a. The rectus abdominis originates from symphysis pubis and the pubic
crest
True False
b. The rectus abdominis inserts onto the 5th, 6th and 7th costal cartilages
and the xiphoid process (T)pyramidalis lies deep to rectus abdominis
True False
c. The external oblique, internal oblique and transversus abdominis are
supplied by the lower 6 thoracic nerves and the ileoinguinal and
ileohypogastric nerves
True False
d. Pyramidalis is supplied by L1
True False
3
a. Is formed by the aponeurosis of the internal oblique muscle
True False
b. Is attached laterally to the anterior superior iliac spine
True False
c. Is attached medially to the posterior superior iliac spine
True False
d. Forms the posterior wall of the inguinal canal
True False
a. Ilioingiunal nerve
True False
b. Femoral artery
True False
c. Femoral branch of the genitor-femoral nerve
True False
d. Lateral cutaneous nerve of the thigh
True False
Question 13: With respect to the blood supply and lymphatic drainage of
the skin of the anterior abdominal wall
4
a. The superior epigastric artery is a branch of the aorta
True False
b. The inferior epigastric artery is a branch of the external iliac artery
True False
c. The lateral aspects of the abdominal wall are supplied by the lumbar
arteries and the deep circumflex iliac artery
True False
d. There is no connection between the veins of the anterior abdominal
wall and the portal vein
True False
Question 14: The following structures are present within the inguinal
canal in the male
a. Testicular artery
True False
b. Vas derefens
True False
c. Inguinal nerve
True False
d. Genital branch of the genitor-femoral nerve
True False
a. The pubic crest forms the base of the superficial inguinal ring
True False
b. The margins of the superficial inguinal ring form the external spermatic
fascia
True False
c. The anterior wall is formed by the aponeurosis of the external oblique
muscle
True False
d. The anterior wall is reinforced laterally by the origin of the internal
oblique muscle
True False
5
Question 1: With respect to the lumbar plexus
True False
b. The femoral nerve enters the thigh anterior to the inguinal ligament
True False
c. The femoral nerve enters the thigh lateral to the femoral sheath
True False
d. The femoral nerve enters the thigh medial to the femoral canal
True False
True False
b. Lies to the right of the cisterna chyli
True False
c. Bifurcates into the left and right common iliac arteries at the level of the first lumbar vertebra
True False
d. Lies to the left of the inferior vena cava
True False
True False
b. Lies anterior to the first part of the duodenum
True False
c. Lies within the lesser omentum
True False
d. Lies posterior to the opening into the lesser sac
True False
a. The lumbar plexus is formed from the posterior rami of the upper 4 lumbar nerves
True False
b. The nerves of the lumbar plexus receive grey rami communicantes from the sympathetic trunk
True False
c. The upper 3 lumbar nerves give off white rami communicantes to the sympathetic trunk
True False
d. The lumbar plexus is formed anterior to the psoas and iliacus muscles
True False
Question 5: With respect to the blood supply to the gastro-intestinal tract
True False
b. The middle colic artery is a branch of the inferior mesenteric artery
True False
c. The ileocolic artery is a branch of the superior mesenteric artery
True False
d. The inferior mesenteric artery is the artery to the hind-gut
True False
a. e) The upper two sympathetic ganglia receive a white ramus communicans from the first and
second lumbar nerves
True False
b. f) Gives off grey rami communicantes to the lumbar spinal nerves
True False
c. g) The left sympathetic trunk is posterior to the inferior vena cava
True False
d. h) Enters the abdomen behind the medial arcuate ligament
True False
True False
b. The celiac artery supplies the lower third of the oesophagus to the duodeno-jejunal junction
(ligament of Treitz)
True False
c. The inferior mesenteric artery is the artery to the mid-gut
True False
d. The superior mesenteric artery supplies the distal half of the second part of the duodenum to
the junction between the proximal 2/3 and distal 1/3 of the transverse colon
True False
True False
b. Lies posterior to the opening into the lesser sac
True False
c. Lies to the right of the bile duct
True False
d. Lies posterior to the portal vein
True False
True False
b. Receives the greater and lesser splanchnic nerves
True False
c. Receives parasympathetic post-ganglionic fibres from the vagus nerve
True False
d. Supplies the proximal 2/3 of the transverse colon
True False
Question 10: With respect to the blood supply to the gastro-intestinal tract
True False
b. The superior rectal artery is a continuation of the inferior mesenteric artery
True False
c. The splenic artery is a branch of the celiac artery
True False
d. The short gastric arteries are branches of the splenic artery
True False
True False
b. The genito-femoral nerve emerges from the lumbar plexus on the anterior surface of psoas
major
True False
c. The genital bramch of the genito-femoral nerve enters the spermatic cord
True False
d. The femoral branch of the genito-femoral nerve supplies the cremaster muscle
True False
True False
b. Pierces the central tendon of the diaphragm at the level of T12
True False
c. Lies medial to the right ureter
True False
d. Is related anteriorly to the opening into the lesser sac
True False
True False
b. Lies anterior to the lesser sac
True False
c. Is a branch of the abdominal aorta at the level of the 12th thoracic vertebra
True False
d. Has three branches ? the right gastric artery, the splenic artery and the hepatic artery
True False
True False
b. The obturator nerve emerges from the lumbar plexus on the medial border of psoas major
True False
c. The obturator nerve crosses the pelvic brim infront of the sacral promontory
True False
d. The obturator nerve crosses the pelvic brim anterior to the common iliac vessels
True False
True False
b. Lies to the left of the cysterna chyli
True False
c. Is related posteriorly to the pancreas
True False
d. Originates behind the left common iliac vein
True False
Question 1: The ascending colon
True False
b. Is related superiorly to the right lobe of the liver
True False
c. Is related anteriorly to the greater omentum
True False
d. Has parasympathetic supply from the vagus nerve via the inferior mesenteric plexus
True False
True False
b. The interlobular ducts are located at the centre of the hepatic lobule
True False
c. The right hepatic duct drains bile from the caudate lobe of the liver
True False
d. The left hepatic duct drains bile from the quadrate lobe of the liver
True False
True False
b. Is related posteriorly to the psoas and iliacus muscles
True False
c. Is related posteriorly to the femoral nerve
True False
d. Is related posteriorly to the lateral cutaneous nerve of the thigh
True False
True False
b. Crosses superior to the uterine artery in the broad ligament
True False
c. Is supplied by the uterine artery within the pelvis
True False
d. Lies more than 5cm lateral to the supra-vaginal cervix
True False
1
a. Is 25cm long
True False
b. Is retro-peritoneal throughout its length
True False
c. The first part is 5cm long and lies on the intercristal plane
True False
d. The first part is related anteriorly to the quadrate lobe of the liver and the gall bladder
True False
True False
b. Lies anterior to the lesser sac
True False
c. Is posterior to the stomach
True False
d. Is related posteriorly to the splenic vein
True False
True False
b. Receives its blood supply from the inferior mesenteric artery
True False
c. Receives its blood supply from branches of the ileocolic artery
True False
d. Is supplied by the left and right caecal arteries
True False
a. Enters the pelvis posterior to the bifurcation of the common iliac artery
True False
b. Enters the pelvis in front of the sacro-iliac joint
True False
c. Is supplied by the renal artery
True False
d. Is supplied by the testicular / ovarian artery
True False
2
a. The lobar arteries supply the renal pyramids
True False
b. The interlobular arteries arise from the lobar arteries
True False
c. The efferent glomerular arteriols arise from the interlobular arteries
True False
d. The renal vein drains directly into the inferior vena cava
True False
a. Is 35cm long
True False
b. Leaves the renal pelvis anterior to the renal vein
True False
c. Is adherent to visceral peritoneum
True False
d. Is separated from the tips of the transverse processes of the lumbar vertebrae by psoas major
True False
a. Parasympathetic supply to the proximal 2/3 is from the vagus via the inferior mesenteric
plexus
True False
b. Parasympathetic supply to the distal 1/3 is from pelvic splanchnic nerves
True False
c. Sympathetic supply to the proximal 2/3 is from the superior mesenteric plexus
True False
d. Sympathetic supply to the distal 1/3 is from the inferior mesenteric plexus
True False
a. Is supplied by the left colic artery, a branch of the inferior mesenteric artery
True False
b. Lymphatic drainage is to the inferior mesenteric nodes
True False
c. Receives sympathetic supply from the pelvic splanchnic nerves
True False
d. Receives parasympathetic supply from the pelvic splanchnic nerves
True False
Question 13: With respect to the nerve supply and lymphatic drainage of the stomach
3
a. The lymphatics drain into the superior mesenteric nodes
True False
b. The anterior vagal trunk is derived mainly from the left vagus nerve
True False
c. The posterior vagal trunk supplies the pancreas
True False
d. The posterior vagal trunk supplies the intestine as far as the splenic flexure
True False
True False
b. Is intra-peritoneal
True False
c. Has the transverse mesocolon attached to its inferior border
True False
d. Has the anterior layer of the greater omentum attached to its inferior border
True False
Question 15: The following structures are present at the porta hepatis
True False
b. Right and left branches of the hepatic artery
True False
c. Right and left branches of the hepatic vein
True False
d. The upper part of the free edge of the lesser omentum
True False
4
Question 1: The pelvic splanchnic nerves
1
Question 4: The levator ani muscle
2
Question 7: The obturator nerve
3
Question 10: The levator ani muscle
4
a. Join the inferior hypogastric plexus directly
True False
b. Join the superior hypogastric plexus directly
True False
c. Provide parasympathetic supply to the hind-gut
True False
d. Provide sympathetic supply to the bladder
True False
5
Question 1: The external anal sphincter
1
Question 4: The superficial perineal pouch in the female
2
Question 7: The superficial perineal pouch in the female
a. Is 2cm long
True False
b. Has its axis directed downwards and forwards from the rectal ampulla
True False
c. Has its anterior and posterior walls in apposition by the tone of the
levator ani muscles
True False
d. Is related posteriorly to the anococcygeal body
True False
3
Question 10: The ischiocavernosus muscle
4
Question 13: The ischio-rectal fossa
5
Question 1: With respect to the bladder and urodynamic studies
1
Question 4: With respect to the uterus
2
Question 7: The sigmoid colon
a. Is retro-peritoneal
True False
b. Is continuous with the rectum at the level of S3
True False
c. Is continuous with the descending colon in front of the right external
iliac artery
True False
d. Is related anteriorly to the uterus
True False
3
Question 10: With respect to the uterus
a. The fundus is that part of the uterus above the entrance of the fallopian
tubes
True False
b. The uterus is 8cm long x 2cm wide by 5cm thick
True False
c. In saggital section, the cavity of the uterus is triangular in shape
True False
d. In coronal section, the cavity of the uterus is represented by a cleft
True False
a. Perineal body
True False
b. Transverse cervical ligament
True False
c. Utero-sacral ligament
True False
d. Pubo-cervical ligament
True False
a. The cervix
True False
b. The bladder
True False
c. The appendix
True False
d. The perineal body
True False
4
Question 13: The ovary
5
Question 1: The pulmonary trunk
a. Is formed from the right brachiocephalic and left internal jugular veins
True False
b. Receives blood from the azygos vein
True False
c. Lies anterior to the aorta in the superior mediastinum
True False
d. Lies posterior to the trachea in the superior mediastinum
True False
1
Question 4: The trachea
2
Question 7: The arch of the aorta has the following branches
3
Question 10: Within the mediastinum
4
a. Communicates with the pulmonary vein
True False
b. Has papillary muscles
True False
c. Is traversed by the moderator band
True False
d. Has papillary muscles which are connected to the cusps of the
tricuapid valve by the chordae tendinae
True False
5
Question 1: The diaphragm
1
Question 4: The internal thoracic artery
2
Question 7: The diaphragm
Question 10: With respect to the lymphatic drainage of the thoracic wall
3
a. Lymphatic drainage of the skin of the anterior chest wall is to the
anterior axillary nodes
True False
b. Lymphatic drainage of the skin of the posterior chest wall is to the
posterior axillary nodes
True False
c. Lymphatic drainage of the anterior part of the intercostal spaces is to
the internal thoracic nodes
True False
d. Lymphatic drainage of the posterior part of the intercostal spaces is to
the para-aortic nodes
True False
a. Has the scalenus anterior muscle inserted onto the scalene tubercle
True False
b. Is crossed by the brachial plexus anterior to the scalenus anterior
muscle
True False
c. Articulates with the transverse process of the 7th cervical vertebra
True False
d. Is palpable throughout its length
True False
4
a. Has a central muscular part and a peripheral tendinous part
True False
b. Has a sternal origin from the posterior surface of the body of the
sternum
True False
c. Has a costal origin from the deep surfaces of the lower 4 ribs and their
costal cartilages
True False
d. Has a right crus originating from the medial arcuate ligament
True False
a. The xiphisternal joint lies opposite the body of the 9th thoracic vertebra
True False
b. The lowest part of the costal margin is formed by the 12th rib
True False
c. The lowest part of the costal margin lies at the level of the 3rd lumbar
vertebra
True False
d. The first rib is palpable throughout its length
True False
5
MAGNETIC RESONANCE IMAGING
• Non-ionising
• The patient is placed in a magnet - the strength of the magnetic field is measured in tesla (T)
and is set at 0.15 - 2 T. This is 10,000 - 20,000 x the earth’s magnetic field. Inside the magnet,
the patient becomes slightly magnetised, generating a combined or net longitudinal
magnetism (M)
• A radio frequency lasting 1ms or less is then sent into the patient by a transmitter - this
produces a rapidly alternating magnetic field which excites protons within the tissues, causing
resonance
• Only mobile protons produce a magnetic resonance signal - those immobilised in large
molecules or in bone do not. The signal is mainly due to water, free or bound. Air has no
hydrogen and produces no signal - appears black. Fat has a higher proton density than other
soft tissue
• The magnetic resonance signal is dependent on the proton density of the tissue and is
greatest immediately after the radiofrequency signal is switched off and decays thereafter as a
result of two independent methods of energy loss or -relaxation - Spin - lattice or T1
relaxation & spin-spin or T2 relaxation
• T1 is the time it takes for the net longitudinal magnetism to recover to 63% of its maximum
value. T1 relaxation is caused by thermodynamic jostling of the excited protons by nearby
molecules - heavy molecules are more effective than light molecules at removing energy from
excited protons
• Thus water bound to the surface of proteins or protons in fat have a shorter T1 while free
water, urine, amniotic fluid, CSF and salt solutions have a long T1. The greater the proportion
of free water in a tissue, the longer is T1
• Atoms in solids and rigid macromolecules are least effective at removing energy and have a
very long T1
• Spin-spin or T2 relaxation is caused by the excited protons (initially in phase) becoming
progressively de-phased as some rotate faster / slower than others
• T2 is the time for the magnetic resonance signal to fall to 37% of its maximum value. De-
phasing occurs because each spinning proton produces a magnetic field which affects
neighbouring protons
• The local variation in magnetic fields is greatest in solid and rigid macromolecules. Compact
bone, teeth, tendons, calculi have a very short T2 and do not produce a lasting signal
• Free water, amniotic fluid, CSF have lighter molecules with rapid thermal motion which
smooths out magnetic fields, producing a longer T2
• Water bound to protein or other large molecules and protons in fat have a shorter T2
• The MRI image maps three properties - the proton density (determines the brightness of the
pixel), T1 and T2
• In T1 weighted images, the shorter the T1 of the tissue, the stronger the signal and the
brighter the pixel - fat is bright as is fatty bone marrow while water and CSF are dark
• In T2 weighted images, the the longer the T2 of the tissue, the stronger the signal and the
brighter the pixel - water and CSF appear brighter than fat
• Generally, tissues with long T1 also have long T2 and those with short T1 have short T2.
Images cannot be weighted for both T1 and T2
• To image small areas, radiofrequency coils (transmitters / receivers) may be placed as close
as possible to the part being imaged. These are similar to head coils used to image the brain
SAFETY
• Magnetic field should not exceed 2.5T in patients, 0.2T in the arms and hands of staff and
0.02T within the body of staff. Strong magnetic fields may result in a sensation of taste and
flashes of light on the retina
• The magnetic field should not be built up too quickly - usually 1-5T per second and no faster
than 20T per second
• Not thought to be any adverse effects on fetal development but MRI is generally not
performed in the first trimester and pregnant staff may be re-deployed
• Switching of magnetic fields may induce eddy currents in nerve fibres causing involuntary
movements, breathing difficulties and ventricular fibrillation. Contra-indicated in patients with
an implanted pacemaker.
• Radiofrequency fields may result in microwave heating - the cornea and testes are particularly
at risk and heating of metallic implants may occur
• Radiofrequencies may affect pacemakers, computers and other equipment relying on electron
flow in a vacuum
• Unstable nuclei have a neutron excess or deficit, are radioactive and decay spontaneously
until they become stable
• Nuclides with a neutron excess decay by releasing a high energy electron (negative beta
particle) while those with a neutron deficit decay by emiting a high energy positive electron
(positive beta particle)
• The product nucleus is usually left with excess energy which is lost by the emission of one or
more gamma photons
• Gamma rays emitted by a particular radionuclide have specific energies whereas beta rays
are emitted with a continuous spectrum of energies up to a maximum which is characteristic
for the radionuclide
• Beta rays are directly ionising and have a range of about 2mm in tissue
• The quantity of radioactive material is measured in the number of disintergrations per second -
the SI unit is the Becquerel (1Bq = 1 disintergration per second). 1 curie (1Ci ) = 3.7 x 10E10
disintergrations per second
• The half-life of a radionuclide is the time taken for its activity to decay to half its original value.
It is not affected by temperature, pressure, electricity or chemical reactions
STABLE ISOTOPES
• Atoms with same number of protons (and electrons) but different number of neutrons with a
stable conformation - these atoms do not decay and do not generate radioactivity
• Examples include Deuterium (heavy water), 13C, 15N, 18O, 34S, 37Cl, 41K
RADIATION HAZARDS
e) Cell death
f) Cell transformation - cancer induction has a latent period of a few years for leukaemia and up to 40
years for solid cancers. Children are more radio-sensitive than adults
• Beta particles / electrons have a short range in tissues and are easily absorbed by several mm
of Perspex or thin sheets of metal
• X-rays and gamma rays do not have a maximum depth of penetration in tissues but simply
undergo continuous attenuation - a residual beam always remains
• The biological damaging effects of heavy particles such as neutrons and alpha particles is 10-
20 times greater than that of electrons as their energy is completely deposited in a shorter
range of tissue
• The EQUIVALENT DOSE of radiation is the absorbed dose multiplied by a radiation weighting
factor which is a measure of the effectiveness of the radiation in inducing cancers compared to
electrons - measured in Joules /Kg (SI unit = seivert, Sv)
• There are no documented risks to the fetus during the first three weeks of gestation (based on
LMP) - that is, before the first missed period. However, high dose procedures such as barium
enemas and abdominal / pelvic CT scans may pose a risk
EXPOSURE
HIGH
0.5 - 5mSv IVU, Barium meal, X-ray lumbar / thoracic spine,
abdomen, pelvis, 99mTc scans of brain, bone, kidney,
Medium liver; lung perfusion scan, thyroid
scan
Low
ELECTROMAGNETIC RADIATION
• Name given to energy travelling in empty space - all have same velocity = speed of light.
Made up of packets / quanta of energy
• Include radio waves (lowest frequency), infrared waves, visible light, ultraviolet light and X &
gamma rays (highest frequency)
• The intensity of the radiation is inversely proportional to the square of the distance from a
point source - Inverse square law
• IONISATION - of air and other gases (makes these rays electrically conducting) and of atoms
in cells - produces adverse biological effects
Other ionising radiation includes some ultraviolet radiation, beta particles and alpha rays
X-RAYS
• Produced when fast-moving electrons impact on a metal target - 99% of the energy of the
electrons is converted into heat and 1% into X-rays
• The absorbed dose is the photon energy deposited per unit mass of a stated material and is
measured in Joules per Kg - the SI unit is the gray (Gy). 1Gy = 1J/Kg
• 1Gy = 100 rad (the rad was the old unit for absorbed dose)
• Particulate forms of radiation such as alpha particles cause more ionisation - a multiplier Q is
used to to express the relative effectiveness of ionisation - Q = 1 for X, Gamma and Beta
radiation, Q = 10 for alpha particles. The product Q. Gy is the sievert (Sv).
• When a beam of X-rays or gamma rays (similar to X-rays but originating from the nucleus)
encounters an object, they can be:
• Attenuation refers to the reduction in photon energy as the beam passes through an obstacle
• The thickness of a material that will reduce the photon energy to half its initial value is called
the half-value layer (HVL) and is a measure of the penetrating power of X-rays or gamma rays
GAMMA IMAGING
• Gamma camera is used to image the distribution of the radionuclide in the patient - the
camera has heavy lead shielding to attenuate unwanted background radiation coming from the
patient or the environment
• Unlike X-rays, the radiation dose delivered to the patient is not dependent on the number of
images taken and is not confined to the region of diagnostic interest
• The ideal radionuclide for imaging should have the following properties:
3) Emit gamma rays of energy 50-300keV - high enough to exit the patient but low enough to be easily
measured. The rays should be mono-energetic
CT SCANNING
• Images a slice of the patient - avoids superposition of adjacent structures that occurs with
conventional X-ray
• Uses X-rays
• Contrast resolution (ability to detect small differences in the attenuation coefficient of adjacent
structures) is better than with conventional X-rays but spatial resolution is poorer.
• The CT number is calculated from the linear attenuation coefficient of each tissue Ut and that
of water Uw as: CT number = 1000(Ut - Uw)/Uw
• The CT number is also known as the Hounsfield number and is -1000 for air and zero for
water
• The radiation dose to the patient from CT is much greater than from conventional X-rays - CT
scans account for 2% of X-ray examinations but 20% of the radiation dose delivered to
patients in the UK.
Question 1: During magnetic resonance imaging
Ionising radiation is not used
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1
False Radiofrequency waves are used
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The patient is
placed in an electromagnetic field
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The brightness
of a pixel is dependent on the proton density of the tissue
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 2: With respect to ultrasound imaging
The resolution along the direction of the beam is finer than that
across the width of the beam
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The scanning
jelly is only used so that the probe will slide along the patient?s
skin
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Bowel gas
helps transmission of sound waves and enables deeper tissues
to be visualised
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Using a
transducer of higher frequency will result in better detail but
only at a shallower depth
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 3: Ultrasound
Cannot be focused
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Can travel
through a vacuum
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Can be
converted into electrical impulses by a transducer
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Is
electromagnetic
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 4: With respect to ultrasound imaging
Penetration increases with increasing ultrasound frequency
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Axial
resolution increases with increasing ultrasound frequency
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Lateral
resolution is dependent on the diameter of the transducer
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Lateral
resolution is decreased by focusing the ultrasound beam
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 5: During magnetic resonance imaging
Air produces excellent magnetic resonance signals
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Fat has a
lower proton density than skeletal muscle
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The magnetic
resonance signal is lowest immediately after the radiofrequency
signal is switched off
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False T1 relaxation
is caused by thermodynamic jostling of excited protons by
surrounding molecules
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 6: Ultrasound
Is a high frequency magnetic field above the audible range
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Medical
ultrasound utilises frequencies in the 1-20MHz range
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Medical
ultrasound utilises frequencies of ~3MHz
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Piezoelectric
crystals are used in ultrasound scanning probes to generate a
focused beam of ultrasound
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 7: With respect to ultrasound imaging
Ultrasound exposure in-utero is associated with an increased
risk of dyslexia
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False There has
been a rise in the occurrence of birth defects with increasing
use of ultrasound
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The process of
microbubble formulation in the presence of an ultrasonic field is
known as cavitation
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Cavitation has
been demonstrated in human systems during medical imaging
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 8: With respect to the use of radiation for medical
imaging
The effective dose from a chest X-ray is higher than from a
chest CT scan
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The effective
dose from a barium meal is lower than from a barium enema
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The effective
dose from a pelvic X-ray is lower than from a chest X-ray
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The effective
dose from a lung perfusion scan is lower than for a chest X-ray
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 9: With respect to SI units
The energy of X-rays and Gamma reya is measured in electron
volts (eV) (T)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The amount of
a radioactive substance is measured in Grays (Gy) (F)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The absorbed
dose of radiation from x-rays and nuclear medicine
examinations is measured in grays (Gy) (T)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Radiation
doses to individuals can be expressed in Sieverts (Sv) to
indicate the degree of risk (T)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 10: The following are examples of stable isotopes
35S
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False 32P
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False 2H (D-2)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False 125I
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 11: During magnetic resonance imaging
The patient is placed in a magnetic field which is about 2x the
earth?s magnetic field
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The strength
of the magnetic field should not exceed 0.1T
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Patients with
ferromagnetic aneurysm clips can safely be imaged
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The cornea
may be damaged by microwave heating
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 12: Accoustic attenuation
Is measured in megahertz (MHz)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Increases with
increasing ultrasound frequency
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Is high in
water and blood
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Is low in air
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 13: During magnetic resonance imaging
Free water, amniotic fluid, and CSF have a longer T2 compared
to fat
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Tissues with a
long T1 have a short T2
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Tissues with a
short T2 have a short T1
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Images can be
weighted for both T1 and T2
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 14: In Doppler ultrasound imaging
The frequency shift is within the audible range
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False A continuous
wave Doppler probe contains two transducers
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False During pulsed
Doppler imaging, only a small fraction of time is spent in the
Doppler mode
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False Continuous
wave Doppler can distinguish between flow in two overlapping
vessels at different depths
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
Question 15: With respect to ultrasound imaging
In colour Doppler imaging, the frequency shift of the echo is
coloured to indicate the direction of blood flow towards or away
from the probe
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False At the power
levels used for medical imaging, no harmful effects to human
tissue have been demonstrated
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The power
output of ultrasound equipment is measured in megahertz
(MHz)
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False The power
output into the patient should be less than 100megaWatts per
square cm
HTMLCONTROL Forms.HTML:Option.1 True
HTMLCONTROL Forms.HTML:Option.1 False
DNA REPLICATION *****
• Reverse transcription
• Based on the primers used, the size of the PCR product can
be predicted and this is used in identification
VECTORS
• DNA species which can enter cells readily, remain stable and
replicate within these cells
NUCLEOTIDES
CHROMOSOME STRUCTURE
• Nucleosomes are organised into 30nm fibres which are then attached
to a central protein scaffolding a series of radial loops.
MESSANGER RNA *****
• The 60S subunit has 5S, 5.8S and 28S rRNA molecules and
about 50 different proteins *
• There is a specific tRNA for each amino acid but some amino
acids are recognised by more than one specific tRNA and
therefore have more than one codon *
TRANSCRIPTION *****
True False
b. The complementary DNA chain is synthesized in the 3 to 5 direction
True False
c. Replication of the leading DNA strand is discontinuous
True False
d. Replication of the lagging DNA strand occurs in Okazaki fragments
True False
a. The primary mRNA transcript is produced only from the exons on the DNA molecule
True False
b. Introns have a sequence that begins with 5?-GU
True False
c. Introns have a sequence that ends with AG-3?
True False
d. The removal of introns occurs in spliceosomes
True False
True False
b. Acts as a template for protein synthesis
True False
c. Contains introns and exons
True False
d. Contains Thymine
True False
True False
b. Contains deoxyribose
True False
c. Is synthesised by RNA polymerase
True False
d. Is synthesized during translation
True False
True False
c. Is mediated by the enzyme DNA polymerase
True False
d. Occurs normally in the human nucleus
True False
True False
b. The 5? end of a nucleotide chain has a phosphate group
True False
c. In DNA, cytosine pairs with adenine
True False
d. Base-pairing occurs through the formation of 3?5?phosphodiester bonds
True False
a. Is polycistronic
True False
b. Has a 5? methylated cap
True False
c. HAS A 3? poly-A tail
True False
d. Is double-stranded
True False
True False
b. Pentose sugar
True False
c. Phosphate group
True False
d. Histones
True False
True False
b. A tetraploid quantity of DNA is present during the G2 phase
True False
c. G2 is the post-mitotic resting phase
True False
d. Cells are generally sensitive to anti-metabolites in the S phase
True False
a. Transcription factors are specific DNA sequences that are essential for the initiation of
transcription
True False
b. The RNA molecule is synthesized in the 3? to 5? direction
True False
c. The 5? methylated cap is added to mRNA within the cytoplasm
True False
d. The 3? poly-A tail is added to mRNA within the nucleus
True False
True False
b. Occurs in DNA viruses
True False
c. Occurs in retroviruses
True False
d. Is used for fluorescent in-situ hybridisation
True False
True False
b. Are arginine and lysine ? rich proteins
True False
c. Are synthesized in the nucleus
True False
d. Are highly negatively charged proteins
True False
Question 13: The following techniques are used to detect the macromolecules listed
True False
b. Western blotting - protein
True False
c. Southern blotting - mRNA
True False
d. Fluorescent in-situ hybridisation - DNA
True False
True False
b. RNA polymerase transcribes the sense strand of the DNA template
True False
c. Alternative splicing may result in some introns persisting in cytoplasmic mRNA
True False
d. The RNA molecule is synthesized in the 3? to 5? direction
True False
True False
b. Has methylated bases
True False
c. Is essential for protein synthesis
True False
d. Makes up 20% of total cellular RNA
True False
ESSENTIAL AMINO ACIDS *****
• These are amino acids which cannot be synthesised by the body and
must be absorbed from the diet
• Include: Histidine, Leucine, Isoleucine, Lysine, Methionine,
Phenylalanine, Threonine, Tryptophan, Valine *
• Cysteine is not an essential amino acid in adults but is an essential amino acid
for the human fetus, and for prematurely born and full term infants for a short period
after birth. *
• Cysteine concentration in maternal plasma is greater than or equal to that in
fetal plasma
• Excess amino acids are neither stored nor excreted but are converted
into glucose, fatty acids or ketone bodies or oxidised for ATP production
• Leucine and lysine are the only strictly ketogenic amino acids *
• During starvation, muscle protein is broken down into amino acids which
are de-aminated and metabolised into pyruvate. Pyruvate can be converted
into alanine, transported to the liver and used for gluconeogenesis *
• Amino acids are filtered in the glomerullus and actively absorbed in the
proximal convoluted tubule *
PROTEIN STRUCTURE *****
• Primary structure - linear sequence of amino acids, including disulphide bonds
• Secondary structure - protein folding into alpha helix and pleated sheets
• Tertiary structure - regional folding between alpha helix and pleated sheets -
dependent on non-covalent forces
• Quaternary structure - only present in proteins with more than one sub-unit - such as
haemoglobin
COLLAGEN *****
• Each collagen peptide is referred to as an alpha chain and is a left handed helical
polypeptide with the basic structure (Gly-A-B) n where one third of A residues are
proline and one third of B residues are hydroxyproline. Collagen is also rich in lysine
and hydroxylysine *
• Alpha chains are synthesised as pro-alpha chains and a signal peptide is excised.
Proline and lysine residues are hydroxylated in the endoplasmic reticulum and golgi
apparatus in a reaction which is dependent on vitamin C as cofactor *
• Glycosylation of alpha chains occurs and three chains are intertwined to form a right
handed triple helix *- tropocollagen which is released into the extracellular matrix
• The propeptide in most forms of collagen is excised in the extracellular matrix and
tropocollagen molecules spontaneously aggregate to form polymeric fibrils held
together through cross-linking between lysine and hydroxylysine residues. These
have a banded appearance on electron microscopy *
• Collagen type I: two identical and one different alpha chain. Makes up 90% of total
collagen and is found in skin, bone, tendon *
• Collagen type II: three identical alpha chains - cartilage and inter-vertebral disc *
• Collagen type III: three identical alpha chains - interstitial collagen in skin and
organs *
• Collagen type IV: two identical and one different alpha chain - basement
membrane *
PROTEIN SYNTHESIS *****
RIBOSOMES
Eukaryotic ribosomes are 80S and dissociate into 40S and 60S subunits
The 40S subunit has an 18S rRNA molecule and about 34 different proteins
The 60S subunit has 5S, 5.8S and 28S rRNA molecules and about 50 different
proteins
However, one amino acid can have more than one codon - the genetic code is
DEGENERATE *
For an amino acid to be added to the protein chain, it must be bound to a tRNA
molecule in a reaction catalysed by aminoacyl tRNA synthetase. There are 20
enzymes, each specific for a particular amino acid. During this reaction, ATP is
hydrolysed to AMP + 2Pi *
The binding of tRNA molecules to the mRNA molecule is less stringent than the
pairing of complementary DNA strands. Pairing may still occur when the third
position on the mRNA codon read from the 5- to 3- end and the first position on the
anticodon on the aminoacyl-tRNA is not an exact match the WOBBLE hypothesis
INITIATION - Protein synthesis begins when the ribosomal subunits come together
with the mRNA molecule and the initiator tRNA molecule carrying the amino acid
METHIONINE *
The start codon is AUG and the first amino acid to be added is always
METHIONINE. This is usually excised during post-translational modification
There are two sites on the ribosome - the P (Peptidyl) site occupied by the peptide
chain and the A (aminoacyl) site to which new aminoacyl-tRNA molecules are added
ELONGATION - two processes - peptide bond formation and translocation
New aminoacyl-tRNAs are added to the A site and a peptide bond is formed between
the carbonyl atom of the P site aminoacyl tRNA and the alpha amino group of the A
site amino acid - catalysed by PEPTIDYL TRANSFERASE
There are mechanisms to check that the correct aminoacyl-tRNA is added to the A
site. Once the peptide bond is formed, the wrong amino acid cannot be removed
Translocation is the process of movement down the mRNAmolecule so that the A site
is emptied for the next aminoacyl-Trna - mediated by TRANSLOCASE and GTP
hydrolysis
• The kidneys excrete two-thirds of the uric acid produced daily; the
remaining one-third is excreted in the stool
• In early pregnancy uric acid levels fall by about one-third but rise to
non-pregnant levels by term *
• Renal diseases with renal failure and prerenal renal failure (e.g.
dehydration)
• Gout.
• Lead poisoning
• Hyperlipidaemia
• Acidosis: lactic acidosis, diabetic ketoacidosis, alcoholic ketosis.
• Pre-eclampsia *
• UREA *****
• The urea cycle occurs in the liver. Blood urea is then taken up and
excreted by the kidneys
• Fumarate formed in the urea cycle can enter the citric acid cycle
True False
b. One amino acid can be coded by more than one codon
True False
c. There are a total of 48 possible codons
True False
d. During the synthesis of aminoacyl-tRNA from amino acids and tRNA, ATP is converted to ADP
and phosphate
True False
a. Histidine
True False
b. Isoleucine
True False
c. Leucine
True False
d. Lysine
True False
True False
b. Are stored in the liver
True False
c. Are converted to glucose
True False
d. Are converted to ketone bodies
True False
a. The reaction between transfer RNA and amino acids is catalysed by the enzyme aminoacyl-
tRNA synthetase
True False
b. There are 64 different aminoacyl tRNA synthetase enzymes
True False
c. The protein chain is synthesized from the C-terminal to the N-terminal
True False
d. A codon is made up of a sequence of four bases
True False
True False
b. The ?Wobble? hypothesis explains the ability of different tRNAs to pair with a specific mRNA
codon
True False
c. New aminoacyl tRNAs are added to the P-site of the ribosomal complex
True False
d. Peptide bond formation is catalysed by the enzyme Peptidyl transferase
True False
Question 6: Collagen
True False
b. Synthesis is inhibited by glucocorticoids
True False
c. Shows a regular banding pattern on electron microscopy
True False
d. Is not found within basement membrane
True False
True False
b. Is raised in serum during normal pregnancy
True False
c. Is raised in serum during treatment with thiazide diuretics
True False
d. Concentration in plasma increases in acute leukaemia
True False
Question 8: Urea
True False
b. Contains two amine groups
True False
c. Is formed by trans-amination from ketoglutarate
True False
d. Excretion is unrelated to protein intake
True False
Question 9: Methionine
True False
c. Cannot be converted to cystine by the fetal liver
True False
d. Is reabsorbed in the proximal convoluted tubule of the kidney
True False
True False
b. Excision of signal sequences
True False
c. Addition of oligosaccharides to asparagines residues
True False
d. Proteolysis
True False
a. Leucine
True False
b. Lysine
True False
c. Isoleucine
True False
d. Tryptophan
True False
True False
b. The last amino acid of every protein is glutamine
True False
c. Protein synthesis takes place on the ribosomes
True False
d. Transfer RNA molecules are specific for particular amino acids
True False
True False
b. Are oxidised for ATP production
True False
c. Undergo transamination with the conversion of alpha-ketoglutarate to glutamate
True False
d. Undergo transamination which converts them into glucose
True False
True False
b. Has hydroxyproline making up one third of the amino acid residues
True False
c. Is synthesised in ribosomes attached to the endoplasmic reticulum
True False
d. Synthesis requires vitamin C which acts as a cofactor
True False
True False
b. Concentration in plasma is raised by corticosteroid therapy
True False
c. Concentration in plasma is higher in males than in females
True False
d. Concentration in plasma characteristically falls during starvation
True False
CARBOHYDRATES
MONOSACCHARIDES *****
• The free aldehyde or ketone can reduce Cu2+ to Cu+ - this forms the basis of Fehling’s and
Benedict’s tests. All monosaccharides are reducing sugars
• Carbon atoms are numbered beginning with the C carrying the aldehyde or ketone group
• D and L forms refer to the configuration of the asymmetry of the C atom furthest away from
the aldehyde or ketone group *
DISACCHARIDES *****
CHOLESTEROL *****
• C27 compound, all derived from acetyl CoA. The acetate units are initially converted to C5
isoprene units *
• High levels of cholesterol and its metabolites reduce the activity of HMG coA reductase,
the enzyme catalysing the committed step in cholesterol synthesis
• Cholesterol is mainly excreted as bile salts and bile acids - glycocholate (glycine
conjugate) or taurocholate (taurine conjugate) *
TRIGLYCERIDES *****
• Simple triglycerides have three identical fatty acids while mixed triglycerides have 2 or 3
different fatty acids *
• Fatty acids removed from triglycerides by the action of lipase and the free fatty acids
degraded by beta-oxidation
• Glucagons, adrenaline and noradrenaline increase plasma free fatty acid concentration
while insulin has the opposite effect *
LIPOPROTEINS *****
• With respect to density: Least dense: Chylomicron < VLDL < LDL < HDL most dense *
Chylomicrons *****
• Synthesized by the gut and transport dietary lipids to tissues via peripheral circulation. *
VLDL *****
• Synthesized in the liver and transports lipids from the liver to other tissues.
• Triglycerides are hydrolysed by lipoprotein lipase. As triglycerides are removed and cholesterol
is esterified with the loss of apoproteins order than apoB-100, VLDL is converted to IDL and
then to LDL
LDL *****
High intracellular cholesterol concentrations reduce the expression of the LDL receptor and inhibit
cellular biosynthesis of cholesterol from acetate *
• HDL extracts cholesterol from cell membranes, converting it into cholesterol esters which
are then transferred to VLDL. VLDL and HDL are taken up by the liver by receptor
mediated endocytosis and cholesterol is excreted in bile in the form of bile salts - the liver
is the only organ that can dispose of significant quantities of cholesterol. *
CITRIC ACID (TRI-CARBOXYLIC ACID) CYCLE *****
• Also oxidises acetyl CoA from fatty acid breakdown and amino acid
degradation products
• Pyruvate is used to make acetyl-CoA, the starting product for the citric
acid cycle.
• For each turn of the cycle, 12 molecules of ATP are produced and one
molecule of GTP *
• The citric acid cycle will operate to a reduced extent unless new
oxaloacetate is formed, because acetyl CoA cannot enter the cycle
unless it condenses with oxaloacetate
• The citric acid cycle also produces intermediates for other biosynthetic
pathways. For instance: *
5) Succinyl-coA used for the synthesis of the porphyrin ring of heme groups.
REGULATION
• Stored mainly in the liver and skeletal muscle - muscle glycogen provides energy for prolonged
muscle contraction while liver glycogen is used to maintain blood glucose levels *
GLYCOGENOLYSIS *****
• Phosphorylase catalyses the removal of glucose units by the phosphorylysis of alpha 1,4
glycosidic bonds up to 4 residues away from a branch point with the release of glucose-1
phosphate *
• The liver, intestines and kidneys have glucose-6-phosphatase which can release glucose from
glucose-6-phosphate. Glycogen in skeletal muscle cannot be converted into glucose as
glucose-6-phosphate cannot leave cells *
• The three residues leading up to a branch point on glycogen are transferred to another part of
the molecule by transferase
• Glycogen synthase catalyses the addition of glucose from UDP-glucose to the non-reducing
end of the glycogen chain, forming alpha-1,4-glycosidic bonds. Glucose residues can only be
added to a chain of five or more residues
• When the chain contains over 11 residues, a branching enzyme transfers seven residues to an
interior site, forming a branch point which must be at least four residues from any pre-existing
branch points
• Phosphorylase exists as a phosphorylated active 'a' form and a dephosphorylated inactive 'b'
form
• Phosphorylation of glycogen synthase converts the active 'a' form to the inactive 'b' form
and glycogen synthesis is inhibited
• INSULIN - results in the phosphorylation and activation of protein phosphatase I *
• Calcium ions released during muscle contraction stimulate glycogenolysis. Skeletal muscle
glycogen cannot be converted into glucose. *
GLYCOLYSIS *****
• Occurs in the cytoplasm and does not require oxygen. Principal energy generating mechanism
in the absence of oxygen of in cells such as RBC which do not have mitochondria *
• Initial reactions involve two phosphorylation steps: initially by hexokinase to form glucose-6-
phosphate (converted to fructose-6-phosphate by isomerase) and then to fructose 1,6
bisphosphate by phosphofructokinase with the hydrolysis of ATP to ADP.
• All reactions in the glycolysis pathway are reversible except those catalysed by hexokinase,
phosphofroctokinase and pyruvate kinase.
GLUCONEOGENESIS *****
Substrates include: *
1) Pyruvate
2) Lactate
3) Oxaloacetate
5) Glycerol
Two molecules of pyruvate are converted to one molecule of glucose with the
hydrolysis of 4 molecules of ATP and two molecules of GTP *
• Unregulated glycolysis and gluconeogenesis would result in the futile consumption of ATP
• Glycolysis is inhibited when ATP and synthetic intermediates are in excess and
gluconeogenesis inhibited when ATP levels are low and ADP levels are high
• The main sites of regulation are at the reactions catalysed by phosphofructokinase (PFK -
glycolysis) and fructose 1,6 bisphosphatase (gluconeogenesis)
• AMP activates PFK (glycolysis and ATP synthesis) but inhibits fructose 1,6 bisphosphatase
• Citrate (citric acid cycle) inhibits PFK (glycolysis) and stimulates fructose 1,6 bisphosphatase
• Glucagon released during starvation inhibits the synthesis of fructose 2,6 bisphosphate while
insulin stimulates its synthesis. Fructose 2,6 bisphosphate activates PFK (glycolysis) and
inhibits fructose 1,6 bisphosphatase
CORI CYCLE
• Occurs during strenuous exercise - NADH formation by glycolysis exceeds the capacity of the
respiratory chain to oxidise it back into NAD+
• Pyruvate is produce by glycolysis in skeletal muscle and converted into lactate by lactate
dehydrogenase with the NADH to NAD+, allowing glycolysis to continue to provide ATP
• Lactate diffuses out of skeletal muscle into blood, is taken up by the liver and converted into
glucose by gluconeogenesis
• Mediated by a single polypeptide enzyme - fatty acid synthase with several enzymatic domains
• The committed step in the pathway is the conversion of acetyl CoA to malonyl CoA by acetyl
CoA carboxylase
• Occurs by the repetitive addition of two carbon units from malonyl CoA which has a three
carbon unit, with the release of CO2
TRIGLYCERIDE SYNTHESIS
• Alpha-glycerol phosphate reacts with 2 molecules of fatty acyl CoA to form phosphatidate
• Triglycerides are converted to one molecule of glycerol and three fatty acids
• Begins in the cytoplasm by the conversion of fatty acids to fatty Acyl CoA - ATP is hydrolysed
to AMP + 2Pi and CoA is required. The reaction is catalysed by Acyl CoA synthetase *
• Fatty Acyl CoA is carried into the mitochondria for beta-oxidation.* This shuttling requires the
presence of carnitine. Acyl Carnitine is formed in the cytosol, carried into the mitochondria then
converted to carnitine + Acyl CoA
• In addition to ATP, NADH and FADH2 are also produced during beta-oxidation
• If the rate of fatty acid oxidation exceeds the rate of carbohydrate breakdown, more acetyl CoA
is generated than can be converted to oxaloacetate - acetyl CoA is then converted to ketone
bodies: acetoacetate and hydroxybutyrate *
• Ketone bodies are produced mainly by the liver and used as fuel particularly by the heart,
muscle and renal cortex. During starvation, the brain may also utilise ketone bodies. The brain,
however, metabolises mainly glucose *
• After a three-day fast, 30% of the energy used by the brain is from ketone bodies. And after 40
days, this goes up to 70%
• Both acetoacetate and beta-hydroxybutyrate are acidic, and if levels of ketone bodies are too
high, ketoacidosis occurs. This happens in untreated Type I diabetes and in alcoholics after
binge drinking and subsequent starvation*
• Ketone bodies are water soluble and may be excreted in the breath (acetone) or in urine
causing ketonuria *
• The fetal brain is an obligate glucose user and cannot utilise ketone bodies*
STARVATION *****
POST-ABSORPTIVE PHASE
• Amino acids are released from skeletal muscle and utilised by the liver for
gluconeogenesis
• Acetyl CoA in the liver is converted to ketone bodies which are used as
fuel mainly by the heart and renal cortex
True False
b. Predominantly contain non-esterified fatty acids
True False
c. Contain more protein by dry weight than high density lipoprotein
True False
d. Attach to specific cell membrane receptors
True False
True False
b. Phosphatidate is produced by the combination of alpha-glycerol phosphate and two molecules
of free fatty acid
True False
c. Diglycerides are produced following the dephosphorylation of phosphatidate
True False
d. Diglycerides combine with one molecule of fatty acyl CoA to form triglycerides
True False
True False
b. Glucagon inhibits glycogenolysis
True False
c. Adrenaline stimulates glycogenolysis
True False
d. Phosphorylase a is phosphorylated and active
True False
Question 4: Glycogen
True False
b. Is predominantly found in cytoplasm
True False
c. Is mainly stored in the liver
True False
d. Is cleaved by phosphorylase to glucose-1-phosphate
True False
True False
b. Amino acids are released from skeletal muscle protein
True False
c. There is increased fatty acid synthesis
True False
d. Phosphofructokinase is inactivated
True False
True False
b. The enzyme glycogen synthase catalyses the addition of glucose units to the non-reducing end
of a chain
True False
c. Glycogen synthase can only add glucose residues to a chain containing three or more
residues
True False
d. New branch points are created at least four residues away from any pre-existing branch points
True False
True False
b. Lipoproteins do not contain any cholesterol
True False
c. Lipoproteins have a hydrophilic core and a hydrophobic surface
True False
d. VLDLs are synthesized in the liver
True False
True False
b. Metabolism is independent of the enzyme phosphorylase
True False
c. Metabolism only generates ATP under aerobic conditions
True False
d. Is entirely intra-cellular
True False
True False
c. Does not require mitochondria
True False
d. May result in the production of ketone bodies
True False
True False
b. Pyruvate is converted to lactate in skeletal muscle
True False
c. Lactate is taken up by hepatocytes and converted to alanine
True False
d. Glucose formed from hepatic gluconeogenesis is utilised by skeletal muscle for glycolysis
True False
True False
b. Is a C19 compound
True False
c. Synthesised from acetate
True False
d. Predominantly excreted unchanged in urine
True False
True False
b. Are a major component of bile
True False
c. Contain triglycerides
True False
d. Are predominantly composed of free fatty acids
True False
True False
b. Glucagon results in the phosphorylation of hormone sensitive lipase
True False
c. Insulin causes dephosphorylation and inactivation of hormone sensitive lipase
True False
d. Glycerol from triglycerides cannot be used for glycolysis
True False
True False
b. Glycogen synthase is phosphorylated
True False
c. Glycogen synthase is activated
True False
d. Glycogen phosphorylase is phosphorylated
True False
True False
b. ATP activates phosphofructokinase
True False
c. Citrate inhibits phosphofructokinase
True False
d. Citrate inhibits fructose 1,6 bisphosphatase
True False
PROTEIN DIGESTION *****
STOMACH
SMALL INTESTINE
• Bicarbonate secreted by the pancreas and biliary tree provides the optimal pH
for enzyme action
• Amino acids, dipeptides and tripeptides are absorbed. Further breakdown of di-
and tri-peptides occurs within intestinal epithelial cells
MOUTH
• Begins in the stomach by the action of lingual lipase secreted by glands at the
back of the tongue and active in the acidic pH of the stomach. Hydrolyses
triglycerides to fatty acids, mono - / di-acylglycerol and glycerol *
• Bile acids are synthesized by the liver and are amphipathic molecules - have
both hydrophilic and hydrophobic parts. Form micelles in solution with the
hydrophobic parts facing inwards and the hydrophilic parts facing outwards *
• Lipids are absorbed from the micelles mainly in the jejunum. The majority of
bile salts are absorbed in the terminal ileum and there is an effective entero-
hepatic circulation *
• Within intestinal epithelial cells, fatty acids containing less than 12 carbon
atoms pass directly into the circulation *
• Fatty acids containing over 12 carbon atoms are metabolised into triglycerides
and incorporated into chylomicrons by the endoplasmic reticulum and golgi
apparatus *
• Chylomicrons enter the intestinal lymphatics and enter the circulation via the
thoracic duct *
ALLOSTERIC ENZYMES
• Enzymes whose activity is altered by the binding of ligands to sites other than
the substrate binding site. Ligand binding may result in activation or inhibition
of enzyme activity. Ligands are allosteric activators or inhibitors *
• If the enzyme is an oligomer (more than one identical subunits), the individual
units are known as protomers. Homotropic interaction is when an allosteric
ligand increases the affinity of another protomer for the same ligand. The
interaction is heterotropic if the affinity for a different ligand is increased.
COFACTORS *****
Non-protein molecules that are necessary for enzyme action. Tow main groups
• COENZYMES - may be metal ions such as Mn2+ or Zn2+ or or complex organic
molecules such as NAD+, NADP+, FAD and Flavine mononucleotide
(FMN) - they are non-covalently bound to the enzyme
• PROSTHETIC GROUPS - are covalently bound to the enzyme at its active site and
include metal ions and organic molecules such as biotin
The protein part of the enzyme without its cofactor is called an apoenzyme
ISOENZYMES
• Catalyse the same reaction and have the same substrate specificity
• Usually different gene products and are expressed in different cells or tissues
• Enzymes are not activated by the products of their reaction otherwise a vicious
cycle would develop. Irreversible covalent modification does not regulate
enzyme activity in vivo but is the mechanism of action of drugs / toxins
PROPERTIES OF ENZYMES *****
• Proteins which catalyse chemical reactions but are unchanged at the end of the
reaction
• Increase the rate at which equilibrium is reached but do not alter the direction
of the reaction or the equilibrium constant
• Enzymes are specific for specific substrates and for the reaction catalysed.
They have an active site which undergoes a conformational change on contact
with substrate to accommodate the substrate (induced fit model). The enzyme-
substrate complex is held together by non-covalent forces - hydrogen and
hydrophobic bonds, electrostatic and van der Waals forces *
• The Km is a measure of the affinity of the enzyme for its substrate - the higher
the Km, the lower the affinity
• The SI unit of enzyme activity is the katal (kat) = the quantity of enzyme in
the presence of which one mole of substrate is converted to product in one
second under optimal conditions for the activity of that enzyme
• The standard unit of enzyme activity U is the amount of enzyme catalysing the
conversion of 1 micromol of substrate per minute under optimal conditions for
the activity of that enzyme
Biochemistry :. Enzymes & digestion :. Module 4: 60 Random questions for MCQ Test
Question 1: With respect to the enzymatic digestion of protein
True False
b. Pepsin cleaves peptide bonds on the NH2 side of sromatic amino acids
True False
c. Enterokinase is secreated by the pancreas
True False
d. Enterokinase converts trypsinogen to trypsin
True False
Question 2: Enzymes
True False
b. Shift the equilibrium point of a reaction towards the synthesis of product
True False
c. Are inactivated at the end of the reaction
True False
d. Increase the equilibrium constant of the reaction catalysed
True False
True False
b. Dipeptides and tripeptides are absorbed by intestinal epithelial cells
True False
c. Trypsin is an endopeptidase
True False
d. Further hydrolysis of peptide bonds occurs within intestinal epithelial cells
True False
Question 4: Isoenzymes
True False
b. Have different substrate specificities
True False
c. Have different substrate affinities
True False
d. Have identical susceptibility to inhibitors
True False
a. Digestive enzymes
True False
b. Polymerases
True False
c. Oxidoreductases
True False
d. Transferases
True False
a. Of the V class have an altered Km but unchanged Vmax in the presence of allosteric ligand
True False
b. Of the V class, in the presence of allosteric ligand have a Lineweaver-Burke plot with an
altered y-intercept
True False
c. Of the V class, in the presence of allosteric ligand have a Lineweaver-Burk plot with an altered
slope
True False
d. Show homotropic interaction if the ligand increases the affinity of another protomer for the
same ligand
True False
True False
b. Lipid esterase requires bile acids for optimal function
True False
c. Bile salts are hydrophobic molecules
True False
d. Bile salts form micelles in solution
True False
a. Hydrolylases
True False
b. Lyases
True False
c. Isomerases
True False
d. Ligases
True False
a. If the substrate concentration is in excess, the initial rate of the reaction is proportional to the
enzyme concentration
True False
b. The initial rate of the reaction is proportional to the substrate concentration for a given enzyme
concentration
True False
c. The Km of an enzyme is the substrate concentration at whch the initial velocity of the reaction
is half the maximum velocity
True False
d. When the substrate concentration = the Km, the initial velocity of the reaction = Vmax
True False
True False
b. Proteolytic activation
True False
c. Regulation of enzyme protein synthesis
True False
d. Irreversible covalent modification
True False
True False
b. Include NAD+
True False
c. Include NADP+
True False
d. Include Flavin adenine dinucleotide
True False
True False
b. Chymotrypsinogen is activated by trypsin
True False
c. Chymotrypsin is a carboxypeptidase
True False
d. Elastase is an endopeptidase
True False
True False
b. Glycerol is produced by the action of lingual lipase on triglycerides
True False
c. Monoglycerides are produced by the action of lingual lipase on triglycerides
True False
d. Lipid esterase is secreted by the pancreas
True False
True False
b. Phospholipase A2 is secreted by the intestinal epithelial cells
True False
c. Pancreatic lipase is inhibited by bile acids
True False
d. Colipase binds to and activates lipase
True False
True False
b. Bind substrates by covalent bonds
True False
c. Undergo a conformational change when the active site comes in contact with substrate
True False
d. Can be activated by phosphorylation
True False
Vitamin A (retinol) *****
Retinol
Recommended daily requirements 750, 500 and 1200 micrograms for adults,
children and lactating women respectively
Vitamin A deficiency
Acts via intracellular receptor interacting with DNA to alter gene expression
Vitamin D deficiency
Vitamin K *****
Fat soluble vitamin - deficiency occurs in fat malabsorption
Present in plant foods as phylloquinone (Vitamin K1)
Synthesised by large intestinal bacteria as menaquinone (Vitamin K2) -
broad spectrum antibiotics destroy intestinal flora and reduce vitamin K
production *
Co-factor in the synthesis of clotting factors - prothrombin (Factor II),
Factors VII, IX, X *
Not stored in significant amounts and deficiency occurs within a few days of
cessation of bile secretion *
Deficiency results in prolonged prothrombin time.
Increased prothrombin time caused by liver failure is not corrected by
vitamin K administration
Should be offered to all neonates (orally) to prevent haemorrhagic disease of
the new born. Intramuscular administration recommended only in neonates
at high risk of haemorrhagic disease
Alpha-tocopherol
Fat-soluble vitamin
Anti-oxidant
Not stored in significant quantities and deficiency occurs within days -weeks
of inadequate intake
Destroyed by cooking
Beriberi *
Dry beriberi presents with heaviness and stiffness of the lower limbs,
weakness, numbness, loss of ankle reflexes. Polyneuropathy may involve the
trunk. Cerebral involvement results in Wernicke-Korsakoff syndrome
Found in many animal and plant foods including dairy products, leafy
vegetables and offal
Not destroyed by cooking
Niacin (B) *
Found in both animal and plant foods. Lost by removing bran from cereal
Synthesised in humans from the amino acid tryptophan this reaction requires
the presence of vitamin B6 (Pyridoxine)
Vitamin B6 (Pyridoxine)
Ascorbic acid
Simple sugar but humans and other primates cannot produce it from glucose
Present in fresh fruit and vegetable - lost during storage and readily leached
out of vegetables placed in water
(Cobalamine / Hydroxycobalamine)
Occurs in:
Anaemia - megaloblastic
Weight loss
Neurological manifestations
b) Dementia
c) Optic atrophy
Iodine - endemic goitre -occurs in areas with a daily intake of less than
150micrograms per day
HYPERVITAMINOSIS *****
True False
b. Deficiency causes beriberi
True False
c. Deficiency causes angular stomatitis
True False
d. Deficiency causes dementia, diarrhoea and dermatitis
True False
True False
b. Is present in plant foods
True False
c. Is not stored by humans in significant amounts
True False
d. Is destroyed by cooking
True False
Question 3: Vitamin A
True False
b. Is derived from beta-carotene
True False
c. Is toxic to tissues in high doses
True False
d. Is required for rhodposin synthesis
True False
True False
b. Deficiency causes peripheral neuropathy
True False
c. Deficiency occurs in patients treated with hydralazine
True False
d. Deficiency occurs in patients treated with penicillin
True False
Question 5: Niacin
True False
c. Deficiency occurs in Hartnup disease
True False
d. Deficiency occurs in carcinoid syndrome
True False
Question 6: Vitamin K
True False
b. Deficiency is treated by intra-muscular injection of phytomenadione
True False
c. Deficiency causes Beriberi
True False
d. Is stored in the liver in sufficient quantities to provide for up to 6 months requirement
True False
a. Is a simple sugar
True False
b. Is an oxidising agent
True False
c. Is involved in the hydroxylation of proline in the synthesis of collagen
True False
d. Can be synthesised from glucose in humans
True False
Question 8: Beriberi
True False
b. Is associated with peripheral vasodilatation
True False
c. Is associated with brisk ankle reflexes
True False
d. May result in Wernicke-Korsakoff syndrome
True False
Question 9: Vitamin E
a. Is a water-soluble vitamin
True False
b. Is mainly found in meat
True False
c. Is an anti-oxidant
True False
d. Deficiency results in xeropthalmia
True False
a. In Crohn?s disease
True False
b. In ulcerative colitis
True False
c. In pregnancy
True False
d. In the Zollinger-Ellison syndrome
True False
True False
b. Deficiency is associated with the Wernicke-Korsakoff syndrome
True False
c. Deficiency is associated with seborrhoeic dermatitis
True False
d. Is a water soluble vitamin
True False
True False
b. Is found exclusively in fish oils
True False
c. Is lost by removing bran from cereal
True False
d. Can be synthesised from tryptophan in humans
True False
a. Optic neuritis
True False
b. Exaggerated ankle reflexes
True False
c. Asymmetrical lower limb weakness
True False
d. Generalised paresis of the insane
True False
Question 14: Deficiency of the following are matched with the correct disease
a. Thiamine ? Pellagra
True False
b. Cyanocobalamine ? Microcytic anaemia
True False
c. Niacin ? Beriberi
True False
d. Ascorbic acid ? Night blindness
True False
True False
b. Does not cross the placenta
True False
c. Deficiency is associated with poor wound healing
True False
d. Deficiency is associated with loss of the enamel of teeth
True False
PRE-IMPLANTATION DEVELOPMENT *****
• The cells (blastomeres) become segregated into the inner cell mass
which forms the embryo proper and the outer cell mass which forms
the placenta and membranes *
• Fluid collects between the cells of the inner cell mass, forming a
blastocyst cavity - day 4 of development
The blastocyst enters the uterine cavity ~day 4, hatches from the zona
Pellucida *
• Appears during the third week and is clearly visible by day 15-16
• Cells from the epiblast migrate towards the primitive streak, detach
from and slip underneath the epiblast to form a third layer between the
epiblast and hypoblast - the intra-embryonic mesoderm
1
• This process is known as gastrulation, at the end of which the
remaining epiblast forms the ectoderm
• Fusion of the neural folds begins in the region of the future neck (4th
somite) and proceeds in ceplalic and caudal directions, forming the
neural tube
• The neural tube remains temporarily open to the amniotic cavity at the
anterior and posterior neuropores *
2
NEURAL CREST *****
1) The truncoconal septum of the heart - migrate via pharyngeal arches. Form
the connective tissue , muscle and parasympathetic ganglia *
5) Sympathetic chain *
6) Parasympathetic ganglia *
7) Melanocytes *
9) Odontoblasts *
3
SPERMATOGENESIS
• Begins at puberty under the influence of testosterone *
• Sertoli cells differentiate and the sex cords become canalised and converted
into seminiferous tubules *
• The dormant primordial germ cells divide by mitosis and then differentiate
into spermatogonia located immediately beneath the basement membrane of
the seminiferous tubules *
• Germ cells are translocated from the basement membrane to the lumen of the
seminiferous tubule as spermatogenesis progresses
• Spermatogonium - (mitotic division) -primary spermatocyte - (first meiotic
division) - secondary spermatocyte - (second meiotic division) - spermatid -
(spermiogenesis) - spermatozoon *
• Spermatozoon obtain full motility in the epididymis *
• Spermatogenesis takes 64 days *
• Primordial germ cells - diploid (2N) *
• Spermatogonia - diploid (2N) *
• Primary spermatocytes - diploid (4N) *
• Secondary spermatocytes - haploid (2N) *
• Spermatides - haploid (N) *
SPERMATOZOON *****
• Head - contains a condensed nucleus capped by the acrosome which contains
hydrolytic enzymes
• Middle-piece - contains large helical mitochondria which generate the power
for swimming
• Tail - contain microtubules forming part of the propulsion system
• Sperm morphology is not important in determining fertility and abnormal
spermatozoa are commonly present in fertile semen *
• Capacitation - changes in the acrosome in preparation for release of hydrolytic
enzymes required to penetrate the zona pellucida - occurs in the female genital
tract
OOGENESIS *****
• Begins during intra-uterine life. The primordial germ cells undergo mitosis
and then differentiate into oogonia *
• By the 5th month in-utero, the number of oogonia is at a maximum - 7
million *
• Oogonia enlarge into primary oocytes. These are surrounded by flattened
follicular cells forming primordial follicles
• Primary oocyte enters prophase of meiosis I and becomes arrested at the
dictyotene stage. Meiosis I is not completed until puberty *
• Primordial follicles begin to degenerate such that at birth, there are 700,000 - 2
million, and at puberty there are 40,000 *
• Several primordial follicles (10-12) begin to mature with each menstrual
cycle and one dominant follicle becomes selected by mechanisms which are
not fully understood *
1
• Follicular cells become cuboidal, forming the primary follicle. A layer of
acellular mucopolysaccharide becomes deposited between the developing
oocyte and the follicular cells, forming the zona pellucida
• Ovulation occurs the moment the secondary oocyte shows spindle formation
and the second meiotic division is only completed if fertilisation occurs *
• The polar body also completes meiosis II, resulting in one definitive oocyte
and three polar bodies *
FERTILIZATION *****
• Occurs in the ampulla of the fallopian tube *
• The spermatozoan undergo capacitation within the female genital tract, during
which seminal plasma proteins and a glycoprotein coat are removed from the
plasma membrane overlying the acrosome
• The spermatozoan force their way through the cumulus oophorus to reach the
zona pellucida to which they are attached aided by sperm receptors
• The acrosome reaction results in the release of hydrolytic enzymes and one
spermatozoan enters the oocyte. This causes immediate release of cortical
granules into the perivitelline space (between the oocyte cell membrane and
the zona pellucida, preventing penetration by other sperm *
2
Question 1: During gametogenesis
a. The lens
True False
b. The inner ear
True False
c. The middle ear
True False
d. The neural creast
True False
1
Question 4: The following are derived from the ectoderm
a. Odontoblasts
True False
b. Meninges
True False
c. The truncoconal septum of the heart
True False
d. Peripheral spinal nerves
True False
Question 6: Fertilisation
2
Question 7: The primordial germ cells
3
True False
b. The first meiotic division is completed during intra-uterine life
True False
c. Primary oocytes are haploid cells
True False
d. The dictyotene stage occurs between the end of the first and the
beginning of the second meiotic divisions
True False
4
Question 13: Concerning oogenesis
a. The blastocyst hatches from the zona pellucida within the fallopian
tube
True False
b. The blastocyst enters the uterine cavity on day 7 after fertilization
True False
c. The outer cell mass gives rise to the embryo proper
True False
d. The inner cell mass gives rise to the placenta and membranes
True False
5
PHARYNGEAL ARCHES
1
PHARYNGEAL POUCHES
2
DEVELOPMENT OF THE GUT *****
FOREGUT
• The dorsal bud forms the head, body and tail while the ventral bud
forms the uncinate process of the pancreas.
• The main pancreatic duct is formed from the distal part of the dorsal
pancreatic duct and the entire ventral duct. Exocrine pancreatic glands
are derived from the foregut endoderm.
• Insulin secretion begins in the fifth month. The origin of the Islets is
controversial.
1
MIDGUT
• Begins distal to the entrance of the bile duct into the duodenum and
ends at the junction between the proximal 2/3 and distal 1/3 of the
transverse colon
• During the 6th week, the midgut herniated into the extra-embryonic
coelom in the umbilical cord and rotates 90 degrees counter clockwise
along the axis of the superior mesenteric artery when viewed from in
front
• The apex of the intestinal loop remains in open connection with the
yolk sac through the vitelline duct, remnants of which form the
Meckel?s diverticulum
• During the 10th week, the midgut retracts into the abdomen,
undergoing a further 180 degrees rotation
HINDGUT
• Extends to the upper two thirds of the anal canal. The distal third of
the anal canal is formed from the ectoderm of the cloaca and the
junction is marked by the pectinate line
• The gut forms a solid cord during the 6th week with re-canalisation
during the 7th - 8th weeks
2
3
DEVELOPMENT OF THE TESTIS *****
• The gonads do not develop male / female differentiation until the end
of the 6th week *
• Primordial germ cells develop from the yolk sac endoderm and migrate
via the dorsal mesentery of the hindgut to reach the gonadal ridge in
the 6th week *
• Primitive sex cords proliferate into medullary cords with Sertoli cells
which produce Mullerian Inhibiting Factor which acts on the ipsilateral
Mullerian tube only, causing degeneration. Mullerian remnants in the
male include the appendix testis and the Utriculus prostaticus *
• The medullary cords remain solid until puberty when they become
canalised, forming the seminiferous tubules *
1
• During the 7th week, the testis begins to detach from the surrounding
mesenchyme and develops a tough connective tissue coat - tunica
albuginae
• The final descent of the testis into the scrotum occurs in the 7th-9th
months*
• The primitive sex cords disintegrate and the centre of the developing
ovary becomes replaced by a vascular stroma, forming the ovarian
medulla *
• The primary oocytes duplicate their DNA and enter the first meiotic
division and become arrested during Prophase I until puberty
• The descent of the ovary is less extensive, coming to lie within the
pelvis. The round ligaments of the ovary and uterus are the equivalent
of the gubernaculums testis *
2
GENITAL DUCTS IN THE FEMALE *****
• The Mullerian ducts persist in the female while the Mesonephric ducts
degenerate. The Mullerian duct gives rise to the Fallopian tube, body of
the uterus, cervix and upper third of the vagina *
• The Mullerian ducts fuse and grow into the urogenital sinus, forming
the sinovaginal bulb which proliferates to form a solid plate of tissue
between the uterus and the urogenital sinus. This becomes canalised
at the end of the 5th month to form the vagina *
• The epoophron and paroophron and Gartners cyst are remnants of the
Mesonephric duct *
• Urogenital septum divides the cloaca into the anorectal canal and the
primitive urogenital sinus - endodermal in origin *
• The upper part of the urogenital sinus forms the bladder (except the
trigone) which is initially continuous with the allantois (obliterated to
form the urachus) *
• The narrow pelvic part of the urogenital sinus forms the prostatic and
membranous urethra in the male *
• With partitioning of the cloaca, the folds form the urethral folds
anteriorly and the anal folds posteriorly
1
• The male / female genitalia are indistinguishable at the end of the 6th
week *
• The urethral groove closes over at the end of the 12th week, forming
the penile urethra. The lining is endodermal in origin. The external
urethral meatus is formed from ectodermal cells from the tip of the
glans which penetrate inwards, forming a cord which is later
canalised *
2
KIDNEY AND URETER *****
Pronephros
Mesonephros *****
1
Bowman’s capsule and excretory tubules. If the ureteric bud is
missing, the kidney does not develop *
2
FETAL ARTERIAL SYSTEM *****
• Each branchial arch receives its own artery during the 4-5th week -
aortic arches
• The first aortic arch disappears apart from a small part - maxillary
artery
• Third arch - common carotid artery and first part of internal carotid
artery
• The forth arch on the left forms part of the arch of the aorta. Right -
proximal part of right subclavian artery
• Vitelline veins - carry blood from the yolk sac to the sinus venosus -
develops into the post-hepatic portion of the inferior vena cava, the
portal vein and superior mesenteric vein
• Umbilical veins - the proximal part of both umbilical veins and the
remainder of the right vein later disappear so that the left vein is the
only one to carry blood from the placenta to the liver
1
• Two umbilical arteries and one umbilical vein with in the umbilical
cord *
• The umbilical vein carries oxygenated blood from the placenta to the
fetus *
• The obliterated umbilical vein forms the ligamentum teres while the
obliterated ductus venosus forms the ligamentum venosum. The
ductus venosus is formed when a direct communication develops
between the left umbilical vein and the hepatocardiac channel *
• Oxygenated blood entering the right atrium from the inferior vena cava
is directed into the left atrium through the foramen ovale *
• Desaturated blood from the superior vena cava flows via the right
ventricle to the pulmonary artery *
• Oxygenated blood then enters the aorta via the left ventricle
• Some blood from the right atrium leaves via the pulmonary artery -
mainly return from the superior vena cava. As the pulmonary circulation
has high resistance, the blood enters the descending aorta through the
ductus arteriosus which connects the pulmonary artery to the aorta *
• The proximal part of the umbilical arteries form the superior vesical
arteries. The obliterated distal part form the medial umbilical
ligaments *
2) The inferior vena cava, mixing with venous blood from the lower extremities
3) The right atrium, mixing with venous blood from the superior vena cava
4) The descending aorta, mixing with blood from the ductus arteriosus
• Blood in the ascending aorta has the highest oxygen saturation and
supplies the heart and brain *
2
• Blood in the right ventricle is therefore mostly de-oxygenated blood
from the superior vena cava. Oxygenated blood passes directly into the
left atrium via the foramen ovale and does not enter the right ventricle *
• Closure of the umbilical vein and ductus venosus - occurs shortly after
closure of the umbilical arteries. The umbilical vein forms the
Ligamentum teres hepatis in the falciform ligament while the ductus
venosus forms the ligamentum venosum *
• Loss of umbilical blood supply reduces venous return via the inferior
vena cava - fall in pressure *
3
Question 1: The following are derived from the mesonephros
a. Blood flows from the left atrium into the right atrium through the
foramen ovale
True False
b. The resistance within the pulmonary vessels is high
True False
c. Oxygenated blood from the placenta is mixed with deoxygenated blood
within the right atrium
True False
d. Oxygenated blood from the placenta is mixed with deoxygenated blood
in the inferior vena cava
True False
1
Question 4: During the development of the genital system in the male
a. Blood from the inferior vena cava is largely directed through the
foramen ovale
True False
b. Most blood from the superior vena cava passes directly from the right
to the left atrium
True False
c. Out-put of the right ventricle is greater than that of the left ventricle
True False
d. Blood in the descending aorta is more oxygenated than that in the
ascending aorta
True False
2
Question 7: With respect to the circulatory system in the fetus
3
system
a. The ductus venosus delivers blood directly into the superior vena cava
True False
b. The umbilical artery returns blood from the placenta
True False
c. The ductus arteriosus carries blood to the lungs
True False
d. Blood returning from the lungs is 90% saturated with oxygen
True False
Question 12: The following are derived from the urogenital sinus
a. Paraurethral glands
True False
b. The greater vestibular glands
True False
c. Gartner?s duct
True False
d. Urachus
True False
4
a. There is an increase in the number of nephrons in each kidney after
birth
True False
b. The mesonephric kidney develops in the pelvis
True False
c. The metanephric kidney develops in the pelvis and ascends into the
abdomen
True False
d. The ureters are endonermal in origin
True False
5
DEVELOPMENT OF THE PLACENTA *****
1
• The distal parts of the villous stems are not vascularised. Here,
cytotrophoblasts proliferate and spread laterally to form a
cytotrophoblastic shell, splitting the syncytiotrophoblast into a definitive
syncytiotrophoblast on the fetal side and the peripheral syncytium on
the decidual side which degenerates and is replaced by fibrinoid
material (Nitabuch's layer)
• The villi oriented towards the uterine cavity degenerate between day
21 and the 4th month to form the chorion laeve. The overlying decidua
degenerates and the chorion laeve comes in contact with the deciduas
of the opposite uterine wall
• The rest of the villi form the chorion frondosum which develops into the
definitive placenta
• Division and modification of the villous tree continues until term. First
trimester villi are larger, have a complete layer of cytotrophoblasts and
have a loose mysenchymal core which is vascularised towards the end
of the first trimester
• At term, the villi are smaller, cytotrophoblasts are few in number, the
syncytiotrophoblast is irregularly thinned. Fetal vessels are sinusoidal
and occupy most of the villous core and lie close to the
syncytiotrophoblast, forming vasculusyncytial membranes which
maximise materno-fetal transfer.
2
TROPHOBLAST INVASION *****
3
PLACENTAL LOBES AND LOBULES
4
AMNIOTIC FLUID *****
· Later formed from transudate from fetal skin and umbilical cord
and diffusion across the amniotic membrane *
1
· Bilirubin concentration falls in the third trimester (except in
haemolytic disease)*
2
PLACENTAL HORMONE PRODUCTION *****
OESTROGENS *
PROGESTERONE *
HCG
1
PLACENTAL TRANSFER
• Feto-placental blood-flow
• Charge of solute
• Protein binding
O2 / CO2 *****
2
WATER TRANSFER
3
ELECTROLYTE TRANSFER *****
4
Molecule Placental transfer
IgM No transfer
Free fatty acids Very limited transfer - essential fatty acids only
ACTH No transfer
5
6
Question 1: With respect to the transfer of solutes across the placenta
1
Question 4: With respect to the development of the placenta
2
Question 7: The human placenta
3
Question 10: Trophoblast
4
a. Intervillous spaces communicate directly with the uterine arteries
True False
b. Decidual cells are derived from endometrial stromal cells
True False
c. At term, each lobe represents a single primary stem villus
True False
d. Cytotrophoblasts are in direct contact with maternal blood
True False
5
AUTONOMIC NERVOUS SYSTEM
• Provides the efferent (motor) pathway linking areas of the brain
concerned with the regulation of the internal environment to specific
effectors such as blood vessels, glands and the heart
• Axons of pre-ganglionic fibres emerge via the ventral root of the spinal
cord together with somatic motor fibres *
• Shortly after the dorsal and ventral roots of the spinal cord fuse,
sympathetic pre-ganglionic fibres leave the spinal nerve trunk and
travel to sympathetic ganglia via white rami communicantes *
1
• The cervical sympathetic chain is represented by the superior, middle
and inferior cervical ganglia which supply the eyes, lacrimal, salivary
glands (superior), heart and respiratory tract (middle & inferior plus
upper 3-4 thoracic ganglia) *
• Innervated by pre-ganglionic fibres from the thoracic spinal cord via the
splanchnic nerves. These fibres synapse directly with the chromaffin cells which are
homologous to sympathetic post-ganglionic neurons and can generate action
potential *
2
ORGAN SYMPATHETIC PARASYMPATHETIC
3
PELVIC SPLANCHNIC NERVES
• The anterior root contains nerves carrying impulses AWAY FROM the
CNS - EFFERENT fibres. Efferent fibres to skeletal muscles are called
motor fibres - cell bodies located in the anterior grey horn of the spinal
cord *
4
in the posterior / dorsal root ganglion with a peripheral axon to the
viscera and a central axon to the CNS *
• On emerging from the foramen, each spinal nerve divides into a large
anterior ramus and a smaller posterior ramus which passes posteriorly
to supply the skin and muscle of the back. The anterior ramus supplies
the antero-lateral body wall and limbs *
• At the root of the limbs, the anterior rami come together to form
complex nerve plexuses
5
Question 1: The parasympathetic nervous system supplies
1
Question 4: Chromaffin cells
2
Question 7: The sympathetic nervous system supplies
3
Question 10: The pelvic splanchnic nerves
4
a. Dilator fibres to the bronchial tree
True False
b. Constrictor fibres to the muscle of the small intestine
True False
c. Inhibitory fibres to the detrusor muscle
True False
d. Constrictor fibres to the coronary arteries
True False
a. Ejaculation
True False
b. Increased secretion by eccrine sweat glands
True False
c. Viscous secretion by the salivary glands
True False
d. Renal vasoconstriction and decreased urine out-put
True False
5
EMBRYOLOGY
Comments 2:
The urinary system develops from the intermediate mesoderm.
During development of the fetus there are 3 overlapping kidney
systems – the pro, meso, and metanephric systems. The
metanephros forms the permanent kidney. Bowman's capsule
and the glomerulus develop together from the mesonephros.
E Endometrium: mesoderm. F
Comments 2:
The mammary gland is derived from the ectoderm as is the tongue epithelium and the
pineal gland. The tongue muscle is derived from mesoderm origin. The mesoderm of the
urogental ridges gives rise to the ovarian stroma, the endometrium is derived from the
endoderm.
B The ureters. F
E Paraurethral glands. T
Comment:
Ureters - develop from the ureteric bud, an outgrowth of the mesonephric duct
close to its opening into the cloaca. Grows into the metanephric mesoderm,
successive divisions forming the renal pelvis, major and minor calyces and
collecting tubules *
A Ureter. F
B Paraurethral glands. T
C Bartholins gland. T
D Urachus. F
E Gartners duct. F
5 In the ovary
Comment:
B Contain cells which have migrated from the wall of the yolk sac T
E Secrete androgens T
10 In spermatogenesis:
11 Concerning oogenesis:
D DNA synthesis does not take place as part of the second meiotic T
division.
Comments 2:
The appearance of the primitive gonad is similar in both sexes
until 42 days after fertilization when seminiferous
differentiation occurs. At 10 weeks conception there is meiotic
entry of oocytes in the medulla of the primitive gonad of the
developing foetus. Gonocytes are diploid and only become
haploid in the gonad via meiosis. Mitosis in oogonia is
completed 7th month of fetal life. The ovary develops from the
primitive cortex not medulla.
D Gubernaculums testis T
E Prostatic utricle F
15 In the fetal cardiovascular system.
Comments 2:
The fetal heart arises from cardiogenic mesoderm. and is
formed by fusion of endocardial tubes. Cardiac pulsation is
present by the 4th week after fertilisation. Oxygenated blood
returning from the placenta goes from the right atrium to the
left atrium (via the foramen ovale). The ductus arteriosus closes
at birth.
Comments 2:
Development of the central nervous system starts at the
beginning of the 3rd week. The neural plate is made of
thickened ectoderm. The anterior neuropore closes at the 18-20
somite stage on day 25. The posterior neuropore closes on day
27.
A Straiated muscle. T
B Blood. T
C Peritoneum. T
E Ovarian stroma. T
C Produces melatonin T
B Is covered by amnion T
A Allantois T
B Extra-embryonic mesoderm. T
C Intestinal loops. T
• Extra-embryonic mesoderm
24 In a neonate at birth:
25 In the vulva:
26 After birth
B Secrete hyaluronidase. F
D Secrete fructose T
E Secrete prostaglandins. T
28 Trophoblast
Comments 2:
Trophoblast - forms the outer layer of the blastocyst, composed
of mitotically active mononucleotide cells called cytotrophoblast
cells. Cytotrophoblast cells can fuse to form large
multinucleated masses called syncytial trophoblast (mitotically
inactive). Both types of cells contribute to the formation of the
placenta. Gives rise to the fetal blood vessels in the placenta.
Small clumps of trophoblast can break away from the villi and
enter the maternal circulation by way of the uterine veins.
Continued invasion of the endometrium by trophoblast cells
establishes direct connections between maternal arteries and
veins and the placental intervillous space. Some cytotrophoblast
cells migrate and penetrate into spiral arteries. The developing
fetus is maintained by a placenta which develops from fetal and
maternal tissues. The fetal portion, formed by the chorion, and
the maternal portion, formed by the decidua basalis – therefore
I would expect them Not to be genetically identical.
2) Oestrogen from the ovary - initially inhibits LH secretion but induces the
pre-ovulatory surge
1
· Main function is the stimulation of the growth of 6-12 primary follicles per
month
· Concentartions are low during childhood, increase during puberty and are
elevated after the menopause
· Stimulates granulosa cell proliferation and also the ovarian stroma to form
the theca interna and externa of the vesicular follicle
· Pulsatile release under influence of higher centres: 8-10 pulses per day in
the adult male; pulsatility in the female is dependent on the menstrual cycle
· MENOPAUSE
2
· Caused by ‘burn-out’ of the ovarian follicles - insufficient to produce enough
oestrogen to suppress FSH secretion or to induce LH surge
PUBERTY
3
INHIBIN
• Two sub-units: alpha and beta. Two types of inhibin (A & B) have
been identified. Have identical alpha sub-unit but different beta sub-
units
ACTIVIN
• Has two sub-units which are identical to the beta sub-units if Inhibin
1
• Suppresses androgen production in the ovary / testis
• Circulating levels increase in the late luteal phase and peak during
menstruation
FOLLISTATIN
2
FOLLICULAR DEVELOPMENT AND OVULATION *****
• The ovum increases in size from < 0.5mm to 10-20mm and the layer of
granulosa cells thickens to form the primary follicle - this may occur
without gonadotropin stimulation
• During the first few days after the onset of menstruation, the FSH and
later LH concentrations begin to rise. FSH stimulates the proliferation
of granulosa cells in 6-12 primary follicles. Stromal proliferation also
occurs to form the theca interna and externa
• The theca externa forms the capsule of the developing follicle while the
theca interna forms an inner glandular and highly vascular layer
1
• The antral follicle secretes increasing amounts of steroids - mainly 17-
beta oestradiol and oestrone (granulosa cells - produced de novo or by
aromatization of androgens from thecal cells). The main androgens
produced are testosterone and androstendione (thecal cells) *
OVULATION *****
2
CORPUS LUTEUM *****
• Thecal cells form smaller lutein cells which produce progesterone and
androgens
• Percentages of the total cell number were as follows: large luteal cells -
4.2%; small luteal cells - 18.5%; fibroblasts - 16.8%; endothelial cells
and pericytes - 52.6%. The remaining 7.9% comprised other
miscellaneous cell types including macrophages *
• The corpus luteum survives for ~14 days in a woman with a regular 28
day cycle
3
ENDOMETRIAL CYCLE
PROLIFERATIVE PHASE
• Cervical mucus becomes copious, watery and more elastic with ferning
when dried. Easily penetrated by sperm
SECRETORY PHASE
4
• Endometrium is 5-6mm thick at the end of the secretory phase
MENSTRUAL PHASE
5
6
SERTOLI CELLS
1
SEMINAL FLUID CONTENT - Produced by the seminal vesicles.
• Fibrinogen
PROSTATE SECRETION
NORMAL SEMEN
2
• Fewer than 1million white blood cells /ml
• pH ~7.5
TESTOSTERONE
3
• Production is mainly under regulation of pituitary LH. During fetal life
in the male, adult concentrations are attained. Levels fall after birth but
rise sharply during puberty
FETUS
4
• SKIN - increased sebaceous gland secretion - DHT
5
OESTROGENS *****
1
OESTROGEN - EFFECTS
2
METABOLISM
• Serum albumin levels are usually decreased (along with the associated
calcium levels). *
3
• Decrease LDL cholesterol
• Increase triglycerides
• Clotting factors - increase in factors II, V, VII, IX, X, XII and especially
VII; decrease of Antithrombin III. Therombogenic *
PROGESTERONE
PROGESTERONE - EFFECTS
4
• FALLOPIAN TUBES - secretory changes in epithelium
5
STRUCTURE OF STEROID HORMONES
2) 19-carbon series: Includes all androgens and the basic structure is the
androstane nucleus
STEROID SYNTHESIS
1
• The rate limiting step in steriodogenesis is the transfer of cholesterol
from the outer to the inner mitochondrial membrane
2
• The reactions converting pregnenolone and progesterone to 17-
hydroxylated products occur in the smooth endoplasmic reticulum
3
• Circulating levels of SHBG are inversely related to weight
4
OESTROGENS *****
1
OESTROGEN METABOLISM
TAMOXIFEN
• Binds oestrogen receptor with affinity 100 - 1,000 times LOWER than
that of oestrogen
2
• Must therefore be present in a concentration 100 - 1,000 times that of
oestrogen maintain inhibition of breast cancer cells - has cytostatic
NOT cytocidal effect
PROGESTOGENS *****
3
THERAPEUTIC USE OF PROGESTOGENS *****
• Treatment of endometriosis
PROGESTERONE METABOLISM
4
RU 486 - MIFEPRISTONE
• 19-nortestosterone derivative
• Binds to the glucocorticoid receptor with very high affinity but a high
dose is required to produce effects because of the high circulating
levels of cortisol (1,000x concentration of progesterone)
ANDROGEN METABOLISM
5
• Adrenal sex steroid production is less important in normal women
6
SEX HORMONE BINDING GLOBULIN AND STEROID TRANSPORT *****
7
Free Albumin-bound SHBG-bound
Oestrogen 1% 30% 69%
• Hyperthyroidism
• Pregnancy
• Oestrogen administration
• Corticosteroids
• Androgens
• Progestogens
• Growth hormone
• Insulin and insulin resistance
• IGF-I
• Increased weight - concentration inversely related to weight
8
Cortisol binding globulin
• Glycoprotein
9
OESTROGEN RECEPTORS
• Two sub-types - alpha and beta - the alpha sub-type has a half life of
4-7h.
1
• Phosphorylation of the receptor and other peptides associated with it
is an important mechanism of regulation - cAMP and protein kinase A
pathways increase the transcriptional activity of the oestrogen receptor
PROGESTERONE RECEPTOR
2
ANDROGEN RECEPTOR
• Progestogens compete with androgens for the receptor and for the 5-
alpha reductase system - dihydroprogesterone which is produced
competes with testosterone and dihydrotestosterone
3
4
ENDOCRINE CHANGES IN PREGNANCY
• Alpha chain similar to alpha chain of FSH, LH, TSH - therefore has
some intrinsic TSH activity
1
- Unique beta chain
• All human tissues make HCG but the placenta is unique in being
able to glycosylate it, increasing the half life and giving biological
activity. Sialic acid residues are essential for the longer half life
• HCG is detectable in the 8 cell stage embryo and takes over from
LH in supporting the corpus luteum about 8 days after ovulation (1 day
after implantation)
• May stimulate androgen production from the early fetal testes and
may also regulate the function of the fetal zone of the adrenal cortex in
early pregnancy thereby influencing placental production of
oestrogens
2
• Maternal HCG ~100IU/L at the time of the first missed period and
peaks at ~100,000IU/L at ~10 weeks gestation
OESTROGEN SECRETION
3
• By 20 weeks gestation, the majority of placental oestrogen
production is from fetal DHEA-Sulphate. The fetus rapidly sulphates
steroids, preventing biological activity.
4
PROGESTERONE SECRETION
5
• The fetal adrenal cortex lacks significant 3-beta-hydroxysteroid
dehydrogenase and isomerase activity and relies on placental
progesterone
6
THE FETAL ADRENAL CORTEX
• Differentiated by 8-9 weeks gestation into a thick inner fetal zone and
a thin outer definitive zone which produces cortisol
• The fetal zone produces large amounts of DHEA & DHEA-S - 3beta
hydroxysteroid dehydrogenase activity is suppressed
1
• Protein hormone secreted by the trophoblast - single polypeptide with
191 amino acids
2
• Pregnancy GHRH and somatostatin do not contribute to maternal
levels
PROLACTIN
3
• Amniotic fluid prolactin is derived from the decidua, while fetal plasma
prolactin is from the fetal pituitary
RENIN-ANGIOTENSIN SYSTEM
4
RELAXIN
5
• Decreased placental oestrogen production (anencephaly, placental
sulphatase deficiency) associated with prolonged pregnancy
6
• Cortisol, in the presence of progesterone, stimulates trophoblast CRH
synthesis. Progesterone is the only major inhibiting factor for CRH
production in placental tissue
• In the sheep, the CRH signal begins in the fetal brain but in humans,
it begins in the uterus
• Levels rise after the onset of labour, particularly in the second stage
7
MENOPAUSE *****
Gonadotrophins
• This decrease in inhibin secretion means that post-menopausal HRT does not
suppress pituitary gonadotrophin secretion - FSH levels cannot therefore be used to
titrate oestrogen replacement *
• FSH levels rise > 20IU/L despite continued menstruation in the peri-menopausal
period but LH levels remain in the normal range *
• FSH and LH levels peak 1-3 years after the menopause, followed by a gradual
decline
Steroidogenesis
• Oestrogen levels do not begin to decline until a woman is within 12 months of the
menopause *
1
• Androgen production continues in the ovaries after the menopause - mainly
androstendione and testosterone. Androstendione levels after the menopause are 50%
those of pre-menopausal women - mostly of adrenal origin *
• DHEA & DHEA-S levels also fall by ~70% after the menopause
• Testosterone production declines by 25% after the menopause but the post-
menopausal ovary secretes more testosterone - stimulated by increased gonadotrophin
levels *
• Ther distal urethra is oestrogen sensitive and atrophy occurs after the menopause. *
2
LEPTIN
• Coded by the ob gene in mice and the Lep gene in humans (located
on chromosome 7q33) - mutations in this gene result in obesity in
mice. However, only a very small minority of overweight humans have
a mutation in the Lep gene or leptin receptor
• Leptin levels are higher in females than in males and higher in post-
menopausal women compared to pre-menopausal women. As weight
increases, leptin levels increase three times as fast in women
compared to men. In girls, leptin levels fall with increasing Tanner
stage of puberty - leptin sensitivity increases at puberty
1
• In overweight individuals, the majority of leptin is unbound, while the
majority is bound in lean individuals
2
Question 1: Human chorionic gonadotrophin
1
Question 4: With respect to follicular development and ovulation
2
Question 7: During the sexual act in the male
Question 8: Leptin
3
Question 10: The following hormones stimulate the proliferation and
branching of breast ducts
a. Prolactin
True False
b. Growth hormone
True False
c. Cortisol
True False
d. Progesterone
True False
4
a. Is thrombogenic
True False
b. Does not bind to albumin
True False
c. Is active when administered orally
True False
d. Is formed in tissues other than the ovary
True False
5
CORTICOTROPIN-RELEASING HORMONE
• Levels in maternal blood and amniotic fluid increase with gestation age
1
• Also inhibits growth hormone release, suppresses fever, appetite and
sexual function and stimulates the sympathetic nervous
system ADRENOCORTICOTROPIC
HORMONE (ACTH)
• Secretion from the anterior pituitary has circadian rhythm and this
regulates cortisol secretion.
2
• Maternal ACTH response to administered ACTH is blunted, indicating
high endogenous levels of CRH and ACTH
3
THYROTROPIN RELEASING HORMONE (TRH)
1) TRH - hypothalamus
3) Growth hormone
4) Cortisol
1
ACTIONS
2
PROLACTIN
ACTIONS
1
GROWTH HORMONE
Secretion is regulated by
2
ACTIONS
3
INSULIN-LIKE GROWTH FACTORS < (IGFs / Somatomedines)
4
5
OXYTOCIN *****
Secretion is stimulated by
• Suckling *
• Labour
ACTIONS
• Stimulate peristalsis *
1
ARGININE VASOPRESSIN (ANTIDIURETIC HORMONE) *****
Secretion is stimulated by
• Angiotensin
• Pain
• Emotional stress
Secretion is inhibited by
• Alcohol *
2
ACTIONS
• Stimulates sodium resorption and urea transport from the lumen into
the interstitial fluid in the medullary collecting ducts
• Large doses of ADH cause smooth muscle contraction and can cause
hypertension and stimulate peristalsis
In pregnancy both the plasma level of vasopressin and the release of vasopressin
following dehydration or water loading remain unchanged*
3
Question 1: Growth hormone
Question 3: Prolactin
1
Question 4: Antidiuretic hormone
2
Question 7: Arginine vasopressin
Question 9: Oxytocin
3
Question 10: Thyroid stimulating hormone
4
Question 13: Corticotropin-releasing hormone
a. Is a glycoprotein
True False
b. Is secreted by the hypothalamus
True False
c. Inhibits growth hormone release
True False
d. Acts by binding to a cytosolic receptor
True False
a. Is released episodically
True False
b. Causes decreased renal tubular absorption of water
True False
c. Causes milk ejection
True False
d. Reduces intestinal peristalsis
True False
5
THYROXINE
PROTEIN BINDING
1
• Does not cross the placenta in significant amounts. The fetal thyroid
produces thyroxine from about 12 weeks gestation.*
ACTION
• Promote growth and development of the brain during fetal life and
childhood
• Lipolytic action on fat stores and increase plasma levels of free fatty
acids. Also increase oxidation of fatty acids *
2
THYROXINE BINDING GLOBULIN
• Levels of FREE T4 may fall slightly in the second and third trimester
• TSH levels fall in the first trimester as HGC levels increase - HGC has
TSH-like action. TSH levels increase in the third trimester to normal
non-pregnant levels*
• Plasma iodine levels fall in pregnancy and iodine uptake by the thyroid
increases 3 fold
3
FETAL THYROID FUNCTION
• Thyroxine production begins at the end of the first trimester and adult
concentrations are reached at term*
• T4 & T3 cross the placenta very poorly and there is a marked materno-
fetal gradient
4
SYNTHESIS OF ADRENAL STEROIDS *****
CORTISOL
1
• Metabolised by the liver, conjugated as glucuronides and excreted in
urine. Urinary 17-hydroxycorticosteroids are also an index of cortisol
secretion*
REGULATION
2
METABOLIC EFFECTS OF CORTICOSTEROIDS
GLUCOSE
• Stimulates appetite
PROTEIN
3
FAT
INFLAMMATION
• Anti-inflammatory
• Decreased fever
4
BONE
FETUS
Facilitate in-utero maturation of lungs, gut, CNS, retina and skin. Increased surfactant
production by fetal lung
• Amenorrhoea / impotence
5
ADRENAL GLAND
ALDOSTERONE SECRETION
• Angiotensin II & III are potent vasoconstrictors and stimulate the synthesis
and secretion of aldosterone from the zona glomerulosa of the adrenal cortex
• ACTH
1
EFFECTS OF ALDOSTERONE
• Also increases sodium absorption from the GI tract and resorption from the
sweat and salivary gland ducts
2
CALCIUM METABOLISM IN PREGNANCY*****
• PTH levels fall to 10-30% of the mean nonpregnant range in the first
trimester but increase again to the normal range by term.
1
VITAMIN D*****
Action of 1,25-dihydroxy D3
• Peptide hormone (84 amino acids) produced by the CHIEF cells of the
parathyroid gland as a pre-prohormone converted to a prohormone
then to PTH
2
• Secretion stimulated by catecholamines and dopamine and inhibited by
1,25-dihydroxy D3
ACTIONS
3
CALCITONIN *****
4
Question 1: The following are metabolic effects of corticosteroids
Question 2: Thyroxine
1
Question 4: Thyroid hormones
Question 5: Cortisol
a. Acute hypoglycaemia
True False
b. ACTH
True False
c. Surgical operation
True False
d. Sepsis
True False
2
Question 7: The following are metabolic effects of corticosteroids
Question 9: Vitamin D
3
Question 10: With respect to thyroid function
a. Is a steroid compound
True False
b. Is a fat soluble vitamin
True False
c. Is poorly absorbed from the GI tract
True False
d. Is synthesised in the skin from 7-dehydrocholesterol following
ultraviolet irradiation
True False
4
Question 13: With respect to the adrenal gland
a. Suppresses appetite
True False
b. Is produced mainly by the thymus gland
True False
c. Stimulates bone resorption
True False
d. Concentration increases in pregnancy
True False
a. Stimulation of gluconeogenesis
True False
b. Stimulation of protein synthesis in muscle tissue
True False
c. Increased glycogen content of the liver
True False
d. Increased glucose utilisation by cells
True False
5
ADRENAL MEDULLA
CATECHOLAMINES
SYNTHESIS
1
Production is stimulated by
2) Cortisol
ACTION
GLUCOSE
2
FAT
CARDIOVASCULAR
SMOOTH MUSCLE
3
OTHERS
• Thermogenesis
4
ISLET OF LANGERHANS
INSULIN SYNTHESIS
INSULIN *****
• Half-life ~ 6 minutes *
1
• Protein disulfide isomerase and cathepsin D are also involved in insulin
metabolism.
• The liver and the kidney are the principal sites for insulin clearance*.
Very little insulin appears in urine
• Glucose *
2
METABOLIC EFFECTS
LIVER
SKELETAL MUSCLE
BRAIN
PROTEIN SYNTHESIS
3
FAT SYNTHESIS
ELECTROLYTES
GLUCAGON *****
• Half-life ~ 6 mins *
Secretion is stimulated by
• Hypoglycaemia
• Amino acids - alanine and arginine (the only factors which stimulate
glucagon as well as insulin secretion)
• Exercise
ACTIONS
4
• Increased hepatic glycogenolysis - activates glycogen phosphorylase
SOMATOSTATIN
1) Increased glucose
5
Question 1: Glucagon
Question 2: Catecholamines
Question 3: Catecholamines
1
Question 4: Insulin
Question 5: Catecholamines
2
Question 7: Glucagon
a. Arginine
True False
b. Glucagon
True False
c. Somatostatin
True False
d. Noradrenaline
True False
Question 9: Insulin
3
Question 10: Insulin
4
Question 13: Glucagon
a. Is a glycoprotein
True False
b. Is bound to serum albumin
True False
c. Has a half life of about 30 minutes within the circulation
True False
d. Has a receptor located in the cell membrane
True False
5
Question 1: The oestrogen receptor
Question 2: Tamoxifen
1
Question 4: The fetal adrenal cortex
2
Question 7: During the synthesis of steroid hormones
a. Insulin
True False
b. Growth hormone
True False
c. Progesterone
True False
d. Cortisol
True False
3
Question 10: The fetal adrenal cortex
4
Question 13: Atrial natriuretic peptide
5
Question 1: Human chorionic gonadotrophin
1
Question 4: With respect to follicular development and ovulation
2
Question 7: During the sexual act in the male
Question 8: Leptin
3
Question 10: The following hormones stimulate the proliferation and
branching of breast ducts
a. Prolactin
True False
b. Growth hormone
True False
c. Cortisol
True False
d. Progesterone
True False
4
a. Is thrombogenic
True False
b. Does not bind to albumin
True False
c. Is active when administered orally
True False
d. Is formed in tissues other than the ovary
True False
5
..
Question 3: Prolactin
1
Question 4: Antidiuretic hormone
2
Question 7: Arginine vasopressin
Question 9: Oxytocin
3
Question 10: Thyroid stimulating hormone
4
Question 13: Corticotropin-releasing hormone
a. Is a glycoprotein
True False
b. Is secreted by the hypothalamus
True False
c. Inhibits growth hormone release
True False
d. Acts by binding to a cytosolic receptor
True False
a. Is released episodically
True False
b. Causes decreased renal tubular absorption of water
True False
c. Causes milk ejection
True False
d. Reduces intestinal peristalsis
True False
5
Question 1: The following are metabolic effects of corticosteroids
Question 2: Thyroxine
1
Question 4: Thyroid hormones
Question 5: Cortisol
a. Acute hypoglycaemia
True False
b. ACTH
True False
c. Surgical operation
True False
d. Sepsis
True False
2
Question 7: The following are metabolic effects of corticosteroids
Question 9: Vitamin D
3
Question 10: With respect to thyroid function
a. Is a steroid compound
True False
b. Is a fat soluble vitamin
True False
c. Is poorly absorbed from the GI tract
True False
d. Is synthesised in the skin from 7-dehydrocholesterol following
ultraviolet irradiation
True False
4
Question 13: With respect to the adrenal gland
a. Suppresses appetite
True False
b. Is produced mainly by the thymus gland
True False
c. Stimulates bone resorption
True False
d. Concentration increases in pregnancy
True False
a. Stimulation of gluconeogenesis
True False
b. Stimulation of protein synthesis in muscle tissue
True False
c. Increased glycogen content of the liver
True False
d. Increased glucose utilisation by cells
True False
5
Question 1: Glucagon
Question 2: Catecholamines
Question 3: Catecholamines
1
Question 4: Insulin
Question 5: Catecholamines
2
Question 7: Glucagon
a. Arginine
True False
b. Glucagon
True False
c. Somatostatin
True False
d. Noradrenaline
True False
Question 9: Insulin
3
Question 10: Insulin
4
Question 13: Glucagon
a. Is a glycoprotein
True False
b. Is bound to serum albumin
True False
c. Has a half life of about 30 minutes within the circulation
True False
d. Has a receptor located in the cell membrane
True False
5
Question 1: The oestrogen receptor
Question 2: Tamoxifen
1
Question 4: The fetal adrenal cortex
2
Question 7: During the synthesis of steroid hormones
a. Insulin
True False
b. Growth hormone
True False
c. Progesterone
True False
d. Cortisol
True False
3
Question 10: The fetal adrenal cortex
4
Question 13: Atrial natriuretic peptide
5
1
1 Adrenocorticotrophic hormone:
A Production is governed by the hypothalamus. T
B Production is maximal about midnight. F
C Is present in the placenta. T
D Is increased in the maternal plasma in pregnancy. T
E Secretion is inhibited by glucocorticoids. T
5 Ganadotrophin-releasing hormone:
A Is adimeric glycoprotein. F
B Is synthesised in the hypothalamus. T
C Stimulates synthesis of follicle-stimulating hormone. T
D Secretion is increased following castration. T
E Pulsatile administration inhabits ovarian steroid production. F
D Serum sodium. F
E Plasma lipids. T
7 Adrenal androgens:
A Are synthesised in the zona glomerulosa of the adrenal cortex. F
B Are secreted in excessive amounts in the presence of 11β- T
hydroxylase deficiency.
C Stimulate protein synthesis. T
D Consist mainly of testosterone. F
E Are secreted in increased amounts in response to rise in T
adrenocorticotrophic hormone.
11 Streroid hormones:
A All contains 20 carbon atoms. F
B Can be produced by structures of urogenital ridge origin. T
C Are mostly activated in the liver. F
D Are predominantly excreted unchanged in the urine. F
E Mainly circulate unbound to carrier proteins. F
17 Adrenaline (epinephrine):
A Stimulates myometrial contractions. F
B Exert its action by alpha receptors only. F
C Constricts the pupils. F
D Causes glycogenolysis. T
E Inhabits the mobilization of free fatty acids. F
18 In hypopituitarism:
A Clinical features of deficiency are usually absent until about 70% T
of the gland has been destroyed.
B Thyroid-stimulation hormone is usually the first hormone to be F
affected.
C Aldosterone secretion is normal. T
D Orthostatic hypotension is common. T
E Hypoglycaemia occurs on fasting. T
4
19 Pituitary gonadatrophin:
A Release is dependent upon hypothalamic function. T
B Secretion increases during pregnancy. F
C Blood levels are raised during lactational amenorrhoea. F
D Release in the puerperium is enhanced by bromocriptine. F
E Release is inhibited by oxytocin. F
23 Thyroxine:
A Exist in the free state in thyroid gland. F
B Is more than 99% protein-bound in plasma. T
C Is released by the fetal thyroid. T
D In the unbound state in plasma is approximately equal in F
concentration to unbound Triiodothyronine.
E Is actively transported across the placenta. F
24 Thyroid hormones:
A Increase oxygen consumption in most metabolically active T
tissues.
B In the circulation are less than 90% bound to protein. F
C Decrease the rate of absorption of carbohydrate from the gut. F
D Increase the circulating cholesterol concentrations. F
E Are essential for skeletal maturation. F
5
26 Iodine:
A Requirements are unchanged by pregnancy. F
B Uptake by the thyroid gland is increased by thyroid-stimulating T
hormone.
C Is excreted by the kidney. T
D Is bound to tyrosine in the thyroid gland. T
E May inhibit thyroxine synthesis. T
29 Parathyroid hormone:
A Is a polypeptide. T
B Increases bone resorption. T
C Decreases phosphate excretion in the urine. F
D Secretion is diminished by an increase in serum ionized calcium T
concentration.
E Decreases the formation of 1,25-dihydroxycholecalciferol. F
30 Parathyroid hormone:
A Decreases the renal excretion of phosphate. F
B Increases calcium resorption from bone. T
C Depresses pituitary activity. F
D Concentrations in blood are raised when the calcium level falls. T
E Increases renal tubular reabsorption of calcium. T
6
31 Parathyroid hormone:
A Increase bone resorption. T
B Concentrations are increase in pregnancy. T
C Reduces phosphate excretion in urine. F
D Increases the formation of 1,25-dihydroxycholecalciferol. T
E Stimulates osteoblasts. F
32 Calcitonin:
A Synthesised in the parathyroid glands. F
B Is a decapeptide. F
C Secretion is increased at serum calcium levels below 1.5 mmol/L F
(6.1mg/100mL).
D Inhibits bone resorption. T
E Increases renal tubular excretion of calcium. T
33 Calcitonin:
A Lower the basal metabolic rate. T
B Concentration is increased in pregnancy. T
C Is released when the blood phosphate level rises. F
D Is produced in the thyroid gland. T
E Release is stimulated by high calcium ion levels. T
34 Calcitonin:
A Increases the basal metabolic rate. F
B Increases the blood calcium level. F
C Is a steroid hormone. F
D Is produced in the parathyroid glands. F
E Release is stimulated by low calcium ion levels. F
35 Calcitonin:
A Suppresses appetite. T
B Is produced mainly in the thymus. F
C Lowers plasma calcium concentrations. T
D Secretion is inhibited by gastrin. F
E Inhibits bone resorption. T
40 Growth hormone:
A Is a protein. T
B Has a molecular weight of 2000 daltons. F
C Secretion is stimulated by hyperglycaemia. F
D Has growth-promoting effects mediated through insuline-like T
growth factors.
E Is synthesised in the hypothalamus. T
41 Growth hormone:
A Promotes protein synthesis. T
B Faciliatates the hepatic synthesis of somatomedin C. T
C Promotes insulin-mediated uptake of glucose. F
D Increases circulating free fatty acids. T
E Stimulates epiphyseal fusion. F
46 Prolactin:
A Release is stimulated by thyrotrophin-releasing hormone. T
B Plasma levels are raised in the first trimester. T
C Release is increased by suckling. T
D May be produced by the decidua. F
E Release is inhibited by metaclopramide. F
47 Prolactin:
A Is secreted by the hypothalamus. F
B Plasma levels are raised in the first trimester of pregnancy. T
C Is identical to placental lactogen. F
D Controls milk ejection. F
E Release is inhibited by dopamine. T
48 Prolactin:
A Release is stimulated by thyrotropin-releasing hormone. T
B Plasma levels are raised in the first trimester of pregnancy. T
C Is identical to human placental lactogen. F
D Control milk ejection. F
E Release is inhibited by metoclopramide. F
50 In human lactation:
A Oestrogens promote development of the breast lobules. F
B Oestrogens promote the milk-producing effect of prolactin on the F
breast.
C Human placental lactogen is essential for milk synthesis. F
9
54 Luteinising hormone:
A Is required for normal corpus luteum survival. T
B Has a half-life in the circulation of 30 hours. F
C Is released in pulses. T
D In the male stimulates testosterone production. T
E Plasma concentrations are increased in postmenopausal women. T
55 Luteinising hormone:
A Is a glycoprotein. T
B Has a molecular weight of approximately 4000 daltons. F
C Stimulates androgen production by ovary. F
D Concentrations in the circulation are high in girls before puberty. F
E Concentrations in the circulation are raised in untreated adult T
with Turner syndrome.
56 Follicle-stimulating hormone:
A Binds to receptors on the cell membrane. T
B Promotes the expression of luteinising hormone receptors. T
C Is responsible for degeneration of the corpus luteum. F
D Is a steroid hormone. F
10
59 Oxytocin:
A Is released episodically. F
B Causes decreased renal tubular reabsorption of water. F
C Is responsible for milk ejection. T
D Reduces intestinal peristalsis. F
E Inhibits prolactin secretion. F
63 Rennin:
A Is secreted by the zona glomerulosa of the adrenal cortex. F
B Is a proteolytic enzyme. T
C Is secreted at an increased rate if the renal perfusion pressure T
falls.
D Acts upon circulating angiotensinogen. T
E Is released in response to an increase in extracellular fluid F
volume.
67 Aldosterone:
A Reduces sodium reabsorption in the proximal convoluted tubule. F
B Reduces sodium absorption in the descending loop of Henle. F
C Increases sodium absorption in the distal convoluted tubule. T
D Increase potassium loss from the tubule. T
E Increases sodium absorption in the collecting tubule. T
68 Aldasterone:
A Secretion is increased by a low potassium intake. F
B Production is reduced in normal pregnancy. F
C Secretion is entirely regulated by the rennin-angiotensin system. F
D Is a principle mineralcorticoid secreted by the adrenal gland. F
E In the kidney, acts on the distal convoluted tubule. T
62 Antidiuretic hormone:
A Is normally synthesised in the hypothalamus. T
B Is secreted by the posterior pituitary gland. T
C Exerts its effect by reducing the glomerular filtration rate. F
D Is an oligapeptide. F
12
70 Argentine vasopressin:
A Reduces the glomerular filtration rate. F
B Controls water loss in the proximal renal tubule. F
C Is synthesized by the posterior pituitary gland. F
D Is released in response to a rise in plasma osmolality. T
E Is released in response to a fall in circulating plasma volume. T
71 Argenin vasopressin:
A Is produced in the hypothalamus. T
B Is a polypeptides. T
C Is structurally similar to prolactin. F
D Controls water reabsorption by kidney. T
E Decreases glomerular filtration. F
72 Vasopressin:
A Is a nanopeptide. T
B Is synthesised in the posterior pituitary gland. F
C Release is increased when plasma osmolality rises. T
D Release is increased by haemorrhage. T
E Plasma concentration is reduced in pregnancy. F
80 Trophoblast:
A Develops from the blastocyst. T
B Gives rise to the fetal blood vessels in the placenta. T
C Enters the maternal circulation during normal pregnancy. T
D Replaces endothelium of pregnant spiral arterioles. T
E Is genetically identical to decidua. F
C 17α-hydroxyprogesterone. F
D Human chorionic gonadotrophin. F
E Oestradiol. T
87 Ovaries secrete:
A Progesterone. T
B Androstenedione. T
C Testosterone. T
D 17β-oestradiol. T
E Aldosterone. F
88 Inhibin:
15
90 Progesterone:
A Is synthesised by trophoblast. T
B Increase myometrial activity. F
C Is predominantly excreted in the urine as pregnanetriol. F
D Binds to cortisol-binding globulin in the circulation. T
E Is synthesised from cholesterol. T
91 Progesterone:
A Is a C -21 steroid. T
B Is synthesised by the ovary before ovulation. T
C Increases ventilation. T
D Rises basal body temperature. T
E Binds to corticotrophin-binding globulin. T
103 Testosterone:
A Is produced only in the gonads. F
B Is mainly excreted unchanged in the urine. F
C Stimulates secretion of luteinising hormone. F
D Circulates in plasma mainly in the free form. F
E Stimulates growth of the prostate gland. T
106 Oestradiol-17β:
A Is synthesized by aromatisation of testosterone. T
B Vasodilates the uterine artery. T
C Suppresses uterine activity by upregulating the oxytocin F
receptor.
D Promotes secondary sexual hair growth in females. F
E Is thrombogenic. T
107 Oestradiol-17β:
A Is synthesized by aromatisation of testosterone. T
B Can be administered orally. T
C Suppresses uterine activity by upregulating the oxytocin F
18
receptor.
D Promotes secondary sexual hair growth in females. F
E Is thrombogenic. T
109 Menopause:
A Is due to failure of the endometrium to respond to oestrogens. F
B Is associated with cessation of steroidogenesis within the ovary. F
C Is associated with a fall in circulating luteinising hormone. F
D Is preceded by a period of enhanced fertility. F
E Results in atrophy of the epithelium of the distal urethra. T
Comment :
110 Concerning androgens in normal premenopausal women:
A 95% of circulating testosterone is derived from peripheral F
conversion of androstenedione.
B The ovaries and adrenals contribute equally to circulating F
androgen concentrations.
C DHEAS (dehydroepiandrosterone sulphate) is derived almost T
exclusively from adrenal glands.
D About50% of circulating testosterone is bound to sex hormone- F
binding globulin (SHBG).
E Testosterone promotes the synthesis of SHBG. F
pancreas.
B Affect the rate of entry of glucose into the β-cells of the F
pancreatic islets.
C Is stimulated by adrenaline. F
D Is stimulated by arginine. T
E Is stimulated more effectively by glucose administered F
interavenously than by glucose administered orally.
1 Adrenocorticotrophic hormone: 83 √
A Production is governed by the hypothalamus. T T T
B Production is maximal about midnight. F F F
C Is present in the placenta. T T T
D Is increased in the maternal plasma in pregnancy. T T T
E Secretion is inhibited by glucocorticoids. T T T
5 Ganadotrophin-releasing hormone: √
A Is adimeric glycoprotein. F F F
B Is synthesised in the hypothalamus. T T T
C Stimulates synthesis of follicle-stimulating hormone. T T T
D Secretion is increased following castration. T T T
E Pulsatile administration inhabits ovarian steroid production. T * F F
D Serum sodium. F F F
E Plasma lipids. T T T
7 Adrenal androgens: √
A Are synthesised in the zona glomerulosa of the adrenal cortex. F F F
B Are secreted in excessive amounts in the presence of 11β- T T T
hydroxylase deficiency.
C Stimulate protein synthesis. T T T
D Consist mainly of testosterone. F F F
E Are secreted in increased amounts in response to rise in T T T
adrenocorticotrophic hormone.
11 Streroid hormones: √
A All contains 20 carbon atoms. F F F
B Can be produced by structures of urogenital ridge origin. T T T
C Are mostly activated in the liver. F F F
D Are predominantly excreted unchanged in the urine. F F F
E Mainly circulate unbound to carrier proteins. F F F
17 Adrenaline (epinephrine): √
A Stimulates myometrial contractions. F F F
B Exert its action by alpha receptors only. F F F
C Constricts the pupils. T * F F
D Causes glycogenolysis. T T T
E Inhabits the mobilization of free fatty acids. F F F
18 In hypopituitarism: √
A Clinical features of deficiency are usually absent until about 70% T T T
of the gland has been destroyed.
B Thyroid-stimulation hormone is usually the first hormone to be T * F F
affected.
C Aldosterone secretion is normal. T T T
D Orthostatic hypotension is common. T T T
E Hypoglycaemia occurs on fasting. T T T
4
19 Pituitary gonadatrophin:
A Release is dependent upon hypothalamic function. T T T
B Secretion increases during pregnancy. F F F
C Blood levels are raised during lactational amenorrhoea. F F F
D Release in the puerperium is enhanced by bromocriptine. F * F * T
E Release is inhibited by oxytocin. F F F
23 Thyroxine: √
A Exist in the free state in thyroid gland. F F F
B Is more than 99% protein-bound in plasma. T T T
C Is released by the fetal thyroid. T T T
D In the unbound state in plasma is approximately equal in F F F
concentration to unbound Triiodothyronine.
E Is actively transported across the placenta. T F F
24 Thyroid hormones: √
A Increase oxygen consumption in most metabolically active T T T
tissues.
B In the circulation are less than 90% bound to protein. F F F
C Decrease the rate of absorption of carbohydrate from the gut. F F F
D Increase the circulating cholesterol concentrations. T * F F
E Are essential for skeletal maturation. F * F * T
5
26 Iodine: √
A Requirements are unchanged by pregnancy. F F F
B Uptake by the thyroid gland is increased by thyroid-stimulating T T T
hormone.
C Is excreted by the kidney. T T T
D Is bound to tyrosine in the thyroid gland. T T T
E May inhibit thyroxine synthesis. T T T
29 Parathyroid hormone: √
A Is a polypeptide. T T T
B Increases bone resorption. T T T
C Decreases phosphate excretion in the urine. F F F
D Secretion is diminished by an increase in serum ionized calcium T T T
concentration.
E Decreases the formation of 1,25-dihydroxycholecalciferol. F F F
30 Parathyroid hormone: √
A Decreases the renal excretion of phosphate. F F F
B Increases calcium resorption from bone. T T T
C Depresses pituitary activity. T * F F
D Concentrations in blood are raised when the calcium level falls. F * T T
E Increases renal tubular reabsorption of calcium. F * T T
6
31 Parathyroid hormone: √
A Increase bone resorption. T T T
B Concentrations are increase in pregnancy. T T T
C Reduces phosphate excretion in urine. T * F F
D Increases the formation of 1,25-dihydroxycholecalciferol. T T T
E Stimulates osteoblasts. F F F
32 Calcitonin: √
A Synthesised in the parathyroid glands. F F F
B Is a decapeptide. F F F
C Secretion is increased at serum calcium levels below 1.5 mmol/L F F F
(6.1mg/100mL).
D Inhibits bone resorption. T T T
E Increases renal tubular excretion of calcium. T T T
33 Calcitonin:
A Lower the basal metabolic rate. T T T
B Concentration is increased in pregnancy. T T T
C Is released when the blood phosphate level rises. T F
D Is produced in the thyroid gland. T T T
E Release is stimulated by high calcium ion levels. T T T
34 Calcitonin: √
A Increases the basal metabolic rate. F F F
B Increases the blood calcium level. F F F
C Is a steroid hormone. F F F
D Is produced in the parathyroid glands. F F F
E Release is stimulated by low calcium ion levels. F F F
35 Calcitonin: √
A Suppresses appetite. T T T
B Is produced mainly in the thymus. T * F F
C Lowers plasma calcium concentrations. T T T
D Secretion is inhibited by gastrin. T * F F
E Inhibits bone resorption. T T T
40 Growth hormone: √
A Is a protein. F * T T
B Has a molecular weight of 2000 daltons. F F F
C Secretion is stimulated by hyperglycaemia. F F F
D Has growth-promoting effects mediated through insuline-like T T T
growth factors.
E Is synthesised in the hypothalamus. F T * F
41 Growth hormone: √
A Promotes protein synthesis. T T T
B Faciliatates the hepatic synthesis of somatomedin C. T T T
C Promotes insulin-mediated uptake of glucose. F F F
D Increases circulating free fatty acids. T T T
E Stimulates epiphyseal fusion. F F F
46 Prolactin: √
A Release is stimulated by thyrotrophin-releasing hormone. T T T
B Plasma levels are raised in the first trimester. T T T
C Release is increased by suckling. T T T
D May be produced by the decidua. T F * T
E Release is inhibited by metaclopramide. F F F
47 Prolactin: √
A Is secreted by the hypothalamus. F F F
B Plasma levels are raised in the first trimester of pregnancy. T T * T
C Is identical to placental lactogen. F F F
D Controls milk ejection. F F F
E Release is inhibited by dopamine. T T T
48 Prolactin: √
A Release is stimulated by thyrotropin-releasing hormone. T T T
B Plasma levels are raised in the first trimester of pregnancy. T T T
C Is identical to human placental lactogen. F F F
D Control milk ejection. F F F
E Release is inhibited by metoclopramide. F F F
50 In human lactation: √
A Oestrogens promote development of the breast lobules. F F F
B Oestrogens promote the milk-producing effect of prolactin on the T * F F
breast.
C Human placental lactogen is essential for milk synthesis. F F F
9
54 Luteinising hormone: √
A Is required for normal corpus luteum survival. T T T
B Has a half-life in the circulation of 30 hours. F F F
C Is released in pulses. T T T
D In the male stimulates testosterone production. T T T
E Plasma concentrations are increased in postmenopausal women. T T T
55 Luteinising hormone: √
A Is a glycoprotein. T T T
B Has a molecular weight of approximately 4000 daltons. F F F
C Stimulates androgen production by ovary. T F * T
D Concentrations in the circulation are high in girls before puberty. T * F F
E Concentrations in the circulation are raised in untreated adult T T T
with Turner syndrome.
56 Follicle-stimulating hormone: √
A Binds to receptors on the cell membrane. T T T
B Promotes the expression of luteinising hormone receptors. T T T
C Is responsible for degeneration of the corpus luteum. F F F
D Is a steroid hormone. F F F
10
59 Oxytocin: √
A Is released episodically. T F * T
B Causes decreased renal tubular reabsorption of water. T * F F
C Is responsible for milk ejection. T T T
D Reduces intestinal peristalsis. F F F
E Inhibits prolactin secretion. F F F
63 Rennin: √
A Is secreted by the zona glomerulosa of the adrenal cortex. F F F
B Is a proteolytic enzyme. F * T T
C Is secreted at an increased rate if the renal perfusion pressure F * T T
falls.
D Acts upon circulating angiotensinogen. T T T
E Is released in response to an increase in extracellular fluid F F F
volume.
67 Aldosterone: √
A Reduces sodium reabsorption in the proximal convoluted tubule. F F F
B Reduces sodium absorption in the descending loop of Henle. F F F
C Increases sodium absorption in the distal convoluted tubule. F * T T
D Increase potassium loss from the tubule. T T T
E Increases sodium absorption in the collecting tubule. T T T
68 Aldasterone: √
A Secretion is increased by a low potassium intake. F F F
B Production is reduced in normal pregnancy. F F F
C Secretion is entirely regulated by the rennin-angiotensin system. F F F
D Is a principle mineralcorticoid secreted by the adrenal gland. T F * T
E In the kidney, acts on the distal convoluted tubule. F * T T
62 Antidiuretic hormone: √
A Is normally synthesised in the hypothalamus. T T T
B Is secreted by the posterior pituitary gland. T T T
C Exerts its effect by reducing the glomerular filtration rate. F F F
D Is an oligapeptide. T * F F
12
70 Argentine vasopressin: √
A Reduces the glomerular filtration rate. F * F * T
B Controls water loss in the proximal renal tubule. F F F
C Is synthesized by the posterior pituitary gland. F F F
D Is released in response to a rise in plasma osmolality. T T T
E Is released in response to a fall in circulating plasma volume. T T T
71 Argenin vasopressin: √
A Is produced in the hypothalamus. T T T
B Is a polypeptides. T T T
C Is structurally similar to prolactin. F F F
D Controls water reabsorption by kidney. T T T
E Decreases glomerular filtration. F * F F
72 Vasopressin: √
A Is a nanopeptide. T T T
B Is synthesised in the posterior pituitary gland. F F F
C Release is increased when plasma osmolality rises. T T T
D Release is increased by haemorrhage. T T T
E Plasma concentration is reduced in pregnancy. F F F
80 Trophoblast: √
A Develops from the blastocyst. T T T
B Gives rise to the fetal blood vessels in the placenta. T T T
C Enters the maternal circulation during normal pregnancy. T T T
D Replaces endothelium of pregnant spiral arterioles. T T T
E Is genetically identical to decidua. F F F
C 17α-hydroxyprogesterone. T * F F
D Human chorionic gonadotrophin. F F F
E Oestradiol. T T T
87 Ovaries secrete: √
A Progesterone. T T T
B Androstenedione. T T T
C Testosterone. T T T
D 17β-oestradiol. T T T
E Aldosterone. F F F
88 Inhibin: √
15
90 Progesterone: √
A Is synthesised by trophoblast. F * T T
B Increase myometrial activity. F F F
C Is predominantly excreted in the urine as pregnanetriol. T * F F
D Binds to cortisol-binding globulin in the circulation. T T T
E Is synthesised from cholesterol. T T T
91 Progesterone: √
A Is a C -21 steroid. F * T T
B Is synthesised by the ovary before ovulation. T T T
C Increases ventilation. T T T
D Rises basal body temperature. T T T
E Binds to corticotrophin-binding globulin. T T T
103 Testosterone: √
A Is produced only in the gonads. F F F
B Is mainly excreted unchanged in the urine. F F F
C Stimulates secretion of luteinising hormone. F F F
D Circulates in plasma mainly in the free form. F F F
E Stimulates growth of the prostate gland. T T T
106 Oestradiol-17β: √
A Is synthesized by aromatisation of testosterone. T T T
B Vasodilates the uterine artery. F * T T
C Suppresses uterine activity by upregulating the oxytocin receptor. T F F
D Promotes secondary sexual hair growth in females. F F F
E Is thrombogenic. T T T
107 Oestradiol-17β: √
A Is synthesized by aromatisation of testosterone. T T T
B Can be administered orally. T T T
C Suppresses uterine activity by upregulating the oxytocin receptor. T * F F
D Promotes secondary sexual hair growth in females. F F F
18
E Is thrombogenic. T T T
109 Menopause: √
A Is due to failure of the endometrium to respond to oestrogens. F F F
B Is associated with cessation of steroidogenesis within the ovary. T F * T
C Is associated with a fall in circulating luteinising hormone. F F F
D Is preceded by a period of enhanced fertility. F F F
E Results in atrophy of the epithelium of the distal urethra. T T T
Comment :
110 Concerning androgens in normal premenopausal women: √
A 95% of circulating testosterone is derived from peripheral F F F
conversion of androstenedione.
B The ovaries and adrenals contribute equally to circulating T * F F
androgen concentrations.
C DHEAS (dehydroepiandrosterone sulphate) is derived almost F * T T
exclusively from adrenal glands.
D About50% of circulating testosterone is bound to sex hormone- F F F
binding globulin (SHBG).
E Testosterone promotes the synthesis of SHBG. T * F F
pancreatic islets.
C Is stimulated by adrenaline. F F F
D Is stimulated by arginine. T T T
E Is stimulated more effectively by glucose administered F F F
interavenously than by glucose administered orally.
1 Adrenocorticotrophic hormone: √ 26
A Production is governed by the hypothalamus. T T
B Production is maximal about midnight. F F
C Is present in the placenta. T T
D Is increased in the maternal plasma in pregnancy. T T
E Secretion is inhibited by glucocorticoids. T T
Comment
Production maximal early morning 4a.m. to 10a.m.
Comments 2:
The production of ACTH is governed through the secretion of CRF from
the hypothalamic nuclei. It governs cortisol secretion where cortisol is
secreted maximally in the morning and concentrations are at a nadir at
midnight. ACTH can be expressed in numerous tissues besides the
pituitary and include the placenta. ACTH concentrations rise in stress,
disease and in pregnancy. Through negative feedback, glucocorticoids
(not mineralocorticoids - aldosterone) switch off ACTH production.
2 The hypothalamus is the site of synthesis of: √
A Oxytocin. T T
B Thyrotrophin-releasing hormone. T T
C α- melanocyte-stimulating hormone F F
D Luteinising hormone. F F
E Gonadaotrophin-releasing hormone. T T
5 Ganadotrophin-releasing hormone: √
A Is adimeric glycoprotein. F F
B Is synthesised in the hypothalamus. T T
2
11 Streroid hormones: √
A All contains 20 carbon atoms. F F
B Can be produced by structures of urogenital ridge origin. T T
C Are mostly activated in the liver. F F
D Are predominantly excreted unchanged in the urine. F F
E Mainly circulate unbound to carrier proteins. F F
17 Adrenaline (epinephrine): √
A Stimulates myometrial contractions. F F
B Exert its action by alpha receptors only. F F
C Constricts the pupils. F F
D Causes glycogenolysis. T T
E Inhabits the mobilization of free fatty acids. F F
Comment
Adrenaline relaxes myometrium via β-receptor. Exert action by α- and β.
18 In hypopituitarism: √
A Clinical features of deficiency are usually absent until about 70% of the T T
gland has been destroyed.
B Thyroid-stimulation hormone is usually the first hormone to be affected. F F
C Aldosterone secretion is normal. T T
D Orthostatic hypotension is common. T T
E Hypoglycaemia occurs on fasting. T T
19 Pituitary gonadatrophin:
A Release is dependent upon hypothalamic function. T T
B Secretion increases during pregnancy. F F
C Blood levels are raised during lactational amenorrhoea. F F
D Release in the puerperium is enhanced by bromocriptine. T F *
E Release is inhibited by oxytocin. F F
Comment
Thyroxine is converted in the tissue to triiodothyronine.
Starvation increase rT.
L-thyroxine has about 5 times the potency of D-thyroxine*
26 Iodine: √
A Requirements are unchanged by pregnancy. F F
B Uptake by the thyroid gland is increased by thyroid-stimulating hormone. T T
C Is excreted by the kidney. T T
D Is bound to tyrosine in the thyroid gland. T T
E May inhibit thyroxine synthesis. T T
29 Parathyroid hormone: √
A Is a polypeptide. T T
B Increases bone resorption. T T
C Decreases phosphate excretion in the urine. F F
D Secretion is diminished by an increase in serum ionized calcium T T
concentration.
E Decreases the formation of 1,25-dihydroxycholecalciferol. F F
30 Parathyroid hormone: √
A Decreases the renal excretion of phosphate. F F
B Increases calcium resorption from bone. T T
C Depresses pituitary activity. F F
D Concentrations in blood are raised when the calcium level falls. T T
E Increases renal tubular reabsorption of calcium. T T
31 Parathyroid hormone: √
A Increase bone resorption. T T
B Concentrations are increase in pregnancy. T T
C Reduces phosphate excretion in urine. F F
D Increases the formation of 1,25-dihydroxycholecalciferol. T T
7
E Stimulates osteoblasts. F F
Comment
During pregnancy and lactation there is increase demand for calcium
and parathyroid gland hypertrophy and become more vascular and
active.
32 Calcitonin: √
A Synthesised in the parathyroid glands. F F
B Is a decapeptide. F F
C Secretion is increased at serum calcium levels below 1.5 mmol/L F F
(6.1mg/100mL).
D Inhibits bone resorption. T T
E Increases renal tubular excretion of calcium. T T
Comment:
CALCITONIN *****
Peptide hormone (32 amino acids) produced by the
parafollicular cells of the THYROID gland.
Secretion is stimulated by a rise in plasma calcium (normal
plasma calcium = 2.2 - 2.6mmol/L).
33 Calcitonin:
A Lower the basal metabolic rate. T T
B Concentration is increased in pregnancy. T T
C Is released when the blood phosphate level rises. F F
D Is produced in the thyroid gland. T T
E Release is stimulated by high calcium ion levels. T T
34 Calcitonin: √
A Increases the basal metabolic rate. F F
B Increases the blood calcium level. F F
C Is a steroid hormone. F F
D Is produced in the parathyroid glands. F F
E Release is stimulated by low calcium ion levels. F F
Comment
Calcitonin decreases appetite, so it reduces the BMR. It decreases blood
calcium.
Stimulated by increased calcium levels, gastrin, secretin, CCK,
glucagons, oestrogen, dopamine and β- agonist.
35 Calcitonin: √
A Suppresses appetite. T T
B Is produced mainly in the thymus. F F
C Lowers plasma calcium concentrations. T T
D Secretion is inhibited by gastrin. F F
E Inhibits bone resorption. T T
GROWTH HORMONE
GROWTH HORMONE
Secretion is regulated by
ACTIONS
46 Prolactin: √
A Release is stimulated by thyrotrophin-releasing hormone. T T
B Plasma levels are raised in the first trimester. T T
C Release is increased by suckling. T T
D May be produced by the decidua. T F *
E Release is inhibited by metaclopramide. F F
47 Prolactin: √
A Is secreted by the hypothalamus. F F
B Plasma levels are raised in the first trimester of pregnancy. T T
C Is identical to placental lactogen. F F
D Controls milk ejection. F F
E Release is inhibited by dopamine. T T
Comment
Prolactin similar to HPL and GH but not identical.
48 Prolactin: √
A Release is stimulated by thyrotropin-releasing hormone. T T
B Plasma levels are raised in the first trimester of pregnancy. T T
C Is identical to human placental lactogen. F F
D Control milk ejection. F F
E Release is inhibited by metoclopramide. F F
50 In human lactation: √
A Oestrogens promote development of the breast lobules. F F
B Oestrogens promote the milk-producing effect of prolactin on the breast. F F
C Human placental lactogen is essential for milk synthesis. F F
D Prolactin stimulates gonadotrophin release. F F
E Oxytocin causes milk ejection. T T
12
54 Luteinising hormone: √
A Is required for normal corpus luteum survival. T T
B Has a half-life in the circulation of 30 hours. F F
C Is released in pulses. T T
13
56 Follicle-stimulating hormone: √
A Binds to receptors on the cell membrane. T T
B Promotes the expression of luteinising hormone receptors. T T
C Is responsible for degeneration of the corpus luteum. F F
D Is a steroid hormone. F F
E Is synthesized in the hypothalamus. F F
Comment:
FOLLICLE-STIMULATING HORMONE (FSH)
· Gonadotropin - produced by the anterior pituitary gland.
Glycoprotein
· Has an alpha and a beta sub-unit
· Functions via a receptor on the cell membrane
14
63 Rennin: √
A Is secreted by the zona glomerulosa of the adrenal cortex. F F
B Is a proteolytic enzyme. T T
C Is secreted at an increased rate if the renal perfusion pressure falls. T T
D Acts upon circulating angiotensinogen. T T
E Is released in response to an increase in extracellular fluid volume. F F
A Rennin is an enzyme. T T
B Angiotensin II is converted to angiotensin I. F F
C Angiotensinogen is globulin. T T
D Rennin release is inhibited by sodium restriction. F T *
E Rennin is present in amniotic fluid. T T
67 Aldosterone: √
A Reduces sodium reabsorption in the proximal convoluted tubule. F F
B Reduces sodium absorption in the descending loop of Henle. F F
C Increases sodium absorption in the distal convoluted tubule. T T
D Increase potassium loss from the tubule. T T
E Increases sodium absorption in the collecting tubule. T T
Comment:
ADRENAL GLAND
ALDOSTERONE SECRETION
• Decreased renal blood flow stimulates renin secretion by the
juxtaglomerular cells of the kidney
• Renin converts angiotensinogen to angiotensin I
• Angiotensin I is converted to angiotensin II & III by angiotensin
converting enzyme
• Angiotensin II & III are potent vasoconstrictors and stimulate the
synthesis and secretion of aldosterone from the zona glomerulosa
of the adrenal cortex
EFFECTS OF ALDOSTERONE
• ~50% is bound to plasma proteins
• Interacts with receptor within the cytoplasm which is translocated
to the nucleus to stimulate transcription. Takes up to 45 minutes for
sodium absorption to be altered
• Increases sodium resorption in the distal renal tubules while
increasing potassium and proton excretion
• Sodium resorption results in water absorption and a rise in
extracellular fluid volume with little change in sodium concentration
• Also increases sodium absorption from the GI tract and
resorption from the sweat and salivary gland ducts.
68 Aldasterone: √
A Secretion is increased by a low potassium intake. F F
B Production is reduced in normal pregnancy. F F
C Secretion is entirely regulated by the rennin-angiotensin system. F F
D Is a principle mineralcorticoid secreted by the adrenal gland. T F *
E In the kidney, acts on the distal convoluted tubule. T T
Comment:
REGULATION OF ALDOSTERONE SECRETION
• Hyperkalaemia - a rise in plasma potassium is the most potent
stimulus for aldosterone secretion.
69 Aldosterone secretion is increased: √
A On standing. T T
B Following haemorrhage. T T
C During pregnancy. T T
D By hypocalcaemia. F F
E On a low sodium diet. T T
62 Antidiuretic hormone: √
A Is normally synthesised in the hypothalamus. T T
B Is secreted by the posterior pituitary gland. T T
C Exerts its effect by reducing the glomerular filtration rate. F F
D Is an oligapeptide. F F
E Secretion is increased when plasma osmolality falls. F F
Comment:
ARGININE VASOPRESSIN (ANTIDIURETIC HORMONE) *****
Polypeptide of 9 amino acids, produced by the supra-optic
nucleus of the hypothalamus and secreted by the pituitary
gland *
Similar structure to oxytocin *
Secretion is stimulated by
Hypovolaemia and hypotension - 10% blood loss would
stimulate ADH secretion. Plays important role in arterial
pressure regulation *
Rise in plasma osmolarity - regulates sodium ion
concentration of extracellular fluid *
18
Angiotensin
Pain
Emotional stress
Nausea and vomiting
Drugs such as morphine and nicotine
Secretion is inhibited by
Decreased plasma osmolarity *
Increased cardiac out-put *
Atrial natruretic peptide
Alcohol *
ACTIONS
Increased water absorption from the renal tubules, in
particular increased permeability of the final third of the
distal tubule and collecting duct *
Increased urine osmolarity and decreased urine flow *
Stimulates sodium resorption and urea transport from the
lumen into the interstitial fluid in the medullary collecting
ducts
Potent vasoconstrictor acts on arteriolar smooth muscle of
skin and splanchnic circulation *
Also causes bradycardia and decreased cardiac output
physiological effect on blood pressure is very small.
However, plays important role during haemorrhage and
dehydration
Has CRF-like activity and stimulates ACTH release
Renal effects of ADH blocked by: hypokalaemia,
hypercalcaemia, lithium therapy
Large doses of ADH cause smooth muscle contraction and
can cause hypertension and stimulate peristalsis
In pregnancy plasma osmolality decreases from 285 to
275mosm/kg
70 Argentine vasopressin: √
A Reduces the glomerular filtration rate. F F
B Controls water loss in the proximal renal tubule. F F
C Is synthesized by the posterior pituitary gland. F F
D Is released in response to a rise in plasma osmolality. T T
E Is released in response to a fall in circulating plasma volume. T T
71 Argenin vasopressin: √
A Is produced in the hypothalamus. T T
B Is a polypeptides. T T
C Is structurally similar to prolactin. F F
D Controls water reabsorption by kidney. T T
E Decreases glomerular filtration. F F
Comment:
19
Comment
HCG is produced by syncytiotrophoblast.
Structurally similar to LH.
α-chain similar to all glycoproteins(LH, FSH, TSH, HCG).
β-chain similar to LH, but β of HCG contains 30 amino acid.
May stimulate androgen production from the early fetal testes and
may also regulate the function of the fetal zone of the adrenal
cortex in early pregnancy thereby influencing placental production
of oestrogens.
75 Human chorionic gonadotrophin: √
A Has a half-life in blood of two hours. F F
B Contains a β chain indistinguishable from that of human luteinising F F
hormone.
C Is produced by the preimplantation blastocyst. F F
D Is responsible for the maintenance of the corpus luteum in early T T
pregnancy.
E May be produced in tissues other than trophoblast. T F *
Comment:
HUMAN CHORIONIC GONADOTROPIN (HCG)
80 Trophoblast: √
A Develops from the blastocyst. T T
B Gives rise to the fetal blood vessels in the placenta. T T
C Enters the maternal circulation during normal pregnancy. T T
D Replaces endothelium of pregnant spiral arterioles. T T
E Is genetically identical to decidua. F F
81 The following cell types are present in the human corpus luteum: √
A Endothelial cells. T T
B Macrophages. T T
C Pericytes. T T
D Fibroblasts. T T
E Granulose cells. T T
Usually breast growth and the growth spurt occur first, followed by the
appearance of pubic, then axillary hair and then menstruation.
84 Concerning the human ovary: √
A Aromatase catalyses the conversion of testosterone to 17β-oestradiol. T T
B Relaxin is synthesised in the corpus luteum. T T
C Inhabin stimulates follicle-stimulating hormone release from the pituitary F F
gland.
D Progesterone decreases the sensitivity of myometrial cells to oxytocin. T T
E Cholesterol is converted to androstenedione in granulose cells. F T *
87 Ovaries secrete: √
A Progesterone. T T
B Androstenedione. T T
C Testosterone. T T
D 17β-oestradiol. T T
E Aldosterone. F F
Comment:
88 Inhibin: √
A Is structurally identical to relaxin. F F
B Is released in pulses. T T
C Is a steroid. F F
D Is produced by the ovarian follicle. T T
E Inhibit the release of follicle-stimulating hormone. T T
Comment:
Comments 2:
Inhibin and relaxin are structurally dissimilar. Ovarian inhibin
exerts a pulsatile release of gonadotrophins. Inhibin is a
glycoprotein hormone produced and secreted by the granulosa and
theca cells of the ovary. It also inhibits FSH secretion.
89 During the normal ovarian cycle: √
A The principle oestrogen secreted is 17-Oestradiol. T T
B The most potent oestrogen is oestriol. F F
C Oestrogen production is maximal by about the 8th day of the cycle. F F
D Oestrogens decrease the secretion of follicle-stimulating hormone. T T
E Oestrogens are synthesized primarily by the ovarian stroma. F F
Comment
Oestrogen production is maximal preovulatary 1 day before LH surge.
The maximum secretion of progesterone from the corpus luteum occurs 8
days after LH surge.
90 Progesterone: √
A Is synthesised by trophoblast. T T
B Increase myometrial activity. F F
C Is predominantly excreted in the urine as pregnanetriol. F F
D Binds to cortisol-binding globulin in the circulation. T T
E Is synthesised from cholesterol. T T
Comment
Pregnanediol glucuronide is the major metabolite of secreted
progesterone. pregnanetriol is a metabolite of adrenocortical hormones.
Progesterone= 80% is bound to albumin.
18% to cortisol binding globulin.
2% is free.
91 Progesterone: √
A Is a C -21 steroid. T T
B Is synthesised by the ovary before ovulation. T T
C Increases ventilation. T T
25
103 Testosterone: √
A Is produced only in the gonads. F F
B Is mainly excreted unchanged in the urine. F F
C Stimulates secretion of luteinising hormone. F F
D Circulates in plasma mainly in the free form. F F
E Stimulates growth of the prostate gland. T T
Comment
Testosterone in most tissues binds very weakly to the receptor and must
28
106 Oestradiol-17β: √
A Is synthesized by aromatisation of testosterone. T T
B Vasodilates the uterine artery. T T
C Suppresses uterine activity by upregulating the oxytocin receptor. F F
D Promotes secondary sexual hair growth in females. F F
E Is thrombogenic. T T
Comment
In female the secondary sex characteristics are due to oestrogen: they
consist of the development of breast. And deposition of body fat. But the
features such as the growth spurt, the growth of axillary and pubic hair
and the development of libido are due to adrenal androgens (mainly
DHEA).
107 Oestradiol-17β: √
A Is synthesized by aromatisation of testosterone. T T
B Can be administered orally. T T
C Suppresses uterine activity by upregulating the oxytocin receptor. F F
D Promotes secondary sexual hair growth in females. F F
E Is thrombogenic. T T
MENOPAUSE
· Average age 50.8 years
· Caused by ‘burn-out’ of the ovarian follicles - insufficient to
produce enough oestrogen to suppress FSH secretion or to induce
29
LH surge
· Oestrogen and progesterone levels fall
· FSH & LH concentrations are elevated which suppress GnRH
secretion.
109 Menopause: √
A Is due to failure of the endometrium to respond to oestrogens. F F
B Is associated with cessation of steroidogenesis within the ovary. T F *
C Is associated with a fall in circulating luteinising hormone. F F
D Is preceded by a period of enhanced fertility. F F
E Results in atrophy of the epithelium of the distal urethra. T T
Comment :
110 Concerning androgens in normal premenopausal women: √
A 95% of circulating testosterone is derived from peripheral conversion of F F
androstenedione.
B The ovaries and adrenals contribute equally to circulating androgen F F
concentrations.
C DHEAS (dehydroepiandrosterone sulphate) is derived almost exclusively T T
from adrenal glands.
D About50% of circulating testosterone is bound to sex hormone-binding F F
globulin (SHBG).
E Testosterone promotes the synthesis of SHBG. F F
Comment:
Source of androgen in women:
Steroid ovary% adrenal% peripheral convertion%
Testosterone 20 30 50
Androstenedione 30 60 10
DHEAS - 80
Dihydrotestosterone 100
----------------------------------------------------------------------------------------
Binding of testosterone to plasma protein:
Male % Femal %
Free 2 1
Albumin-bound 38 19
SHBG-bound 60 80
--------------------------------------------------------------------------------------
SHBG levels are decreased by testosterone and increased by oestradiol.
Levels are therefore highest in females during pregnancy and lowest in
male after puberty.
Synthesis of SHBG is stimulated by: oestrogen and thyroxine, and
inhibited by: insulin, GH, androgenic drugs and progestagens.
Concentration are lower in obese subjects.
111 In a woman of reproductive age, serum concentrations of the √
following hormones exhibit a recognized pattern of diurnal variation:
A Progesterone. F F
B Melatonin. T T
C Cortisol. T T
D Oestrone. F F
E Follicle-stimulating hormone. F F
30
Comment
Pineal gland lies posterior to the 3rd ventricle.
Innervated by postganglionic sympathetic nerves (nerve canarii).
Decreases in size at puberty.
acid
Oxytocin Nanopeptide 9 1-4 min
Aldosterone 20 min
Vasopressin Nanopeptide 9
Somatostatin Cyclic peptide 14 1640
KARYOTYPING *****
CHROMOSOME HETEROMORPHISMS
• These are variations in the amount of DNA present in particular chromosomes from
different individuals caused by variations in the size of repetitive DNA - they are
inherited rather than acquired
• The Y chromosome shows the greatest variation while the X chromosome shows
the least variation
• There are 4 main groups of heteromorphisms
CHROMOSOME STRUCTURE
HISTONES *****
• Basic nuclear protein around which the DNA molecule is tightly bound
• Makes up about 50% of the mass of a chromosome
• Rich in lysine or arginine (~25%, these are basic amino acids)
• The genes coding for histone protein are clustered and tandemly repeated 30-40
times in humans
AUTOSOMAL DOMINANT INHERITANCE *****
LYONISATION *****
MOSAICISM *****
• This requires IVF with biopsy of the embryo at the 6-10 cell stage. The indications are as an
alternative to pre-natal diagnosis in a couple known to be at risk of transmitting a genetic
diaorder. It can also be used as a primary tool in couples undergoing IVF treatment.
• Most centres use cleavage stage embryo biopsy. There are no reports of blastocyst
biopsy / use of inner cell mass cells.
• Zona drilling may be performed using acid Tyrodes solution, laser or by partial zona
dissection
• Compaction of the embryo begins to occur after the 8 cell stage with the formation of
inter-cellular junctions - this is Ca2+ / Mg2+ dependent. Biopsy is therefore facilitated
by using Ca2+ / Mg2+ free culture medium
• Removal of both polar bodies is required for accurate diagnosis. Can be performed
simultaneously or sequentially
Pre-implantation genetic diagnosis is currently possible in the following conditions. The number of
conditions is however constantly increasing.
a) Cystic fibrosis
c) Beta-thalassaemia
d) Congenital adrenal hyperplasia
f) Marfan?s syndrome
g) Osteogenesis imparfecta
h) Fragile X syndrome
j) Huntington?s chorea
k) Myotonic dystrophy
l) Charcot-Marie-Tooth disease
n) Retinitis pigmentosum
• Pre-implantation diagnosis uses a single cell for diagnosis. This is made possible by
the use of PCR technology, amplifying fragments of DNA thousands of times. FISH
uses fluorescent tagged DNA probes that bind to specific DNA sequences. Restriction
fragment length polymorphisms can be used to identify abnormal gene sequences
PCR PROBLEMS
• Contamination by DNA from the environment, laboratory staff and other cells including
sperm and cumulus cells - for this reason, ICSI(Intra-Cytoplasmic Sperm Injection) is
used prior to pre-implantation genetic diagnosis
• Allele drop-out: This is the preferential amplification of one allele only and is particularly
important in autosomal dominant conditions. If the mutated allele drops out, the
embryo would be erroneously diagnosed as normal.
• It is now recognised that 1-2 cells biopsied from the blastocyst are not necessarily
representative of the rest of the embryo
• Mosaicism does not affect sexing as female cells would have to appear in a male
embryo (or vice versa)
• Restriction enzymes are used to cut DNA at precise points producing a collection of
DNA fragments of precisely defined length.
Karyotype is typically available after 2-3 weeks while results of rapid diagnostic tests can be available
within 24-48h. However, rapid tests only analyse specific chromosomes, typically 13, 18, 21 and X & Y if
required
• Three chromosomes can be detected at the same time (three flurochromes available - red,
blue and green)
• Commercial kits are available for FISH and this is therefore a relatively inexpensive technique
• Designed to detect specific aneuploidies and will not detect other abnormalities or structural
chromosomal defects
1) Maternal cell contamination - this will not be detectable if the fetus is female.
3) DNA polymorphism causing cross-hybridisation of DNA probe with other DNA locations
4) Mosaicism - this may only be detected if a sufficient cells (at least 100) are used for analysis
• Relies on the analysis of non-coding regions of DNA which show a wide variation in size
between different individuals
• These regions are amplified by PCR and separated on a gel according to size
• If three copies are present of different sizes, this is easily detectable bi differences in migration
on the gel
• If two copies are present of identical size, this will also be detectable because the total
quantity of DNA can also be determined
• Will not detect abnormalities in other chromosomes (apart from those analysed) or structural
anomalies
• QF-PCR is not reliable when used to analyse a single cell and FISH is the preferred method
for pre-implantation genetic diagnosis
• DNA from sample is labelled with one flurochrome (say red) and compared with a normal
reference DNA labelled green
• The two DNA samples are added to a slide containing multiple metaphases from a normal
male for hybridisation
• Computer aided analysis is used to determine the red : green ratio for every chromosome and
therefore determine the copy number
· Result from the fertilisation of one oocyte by one sperm, the resulting zygote
splitting into two during the early stages of development
· 70% are monochorionic and diamniotic and 30% are dichrionic and
diamniotic. Monochorionic monoamniotic twins are rare
a. Allele drop-out
True False
b. Contamination by sperm DNA
True False
c. Contamination by DNA from laboratory personnel
True False
d. Confined placental mosaicism
True False
True False
b. The G2 phase occurs before the M phase
True False
c. Interphase includes the G1 and G2 phases but not the S phase
True False
d. The nucleus in the G2 phase contains twice the diploid amount of DNA
True False
True False
b. Hereditary spherocytosis ? X-linked recessive
True False
c. Achondroplasia ? autosomal dominant
True False
d. Alport syndrome ? X-linked recessive
True False
a. Chromosomes can be stained with quinacrine and examined under ultra-violet light
True False
b. In G-banding, the dark bands contain mainly active genes
True False
c. The banding pattern of each chromosome is characteristic
True False
d. G-banding is a sensitive method of detecting individual missing genes
True False
True False
b. G-banding can detect point mutations
True False
c. G-banding can detect chromosomal translocations
True False
d. G-banding is used to demonstrate highly repetitive micro-satellite repeat DNA at the
centromeres
True False
a. May be identical
True False
b. May be monochorionic
True False
c. May be monoamniotic
True False
d. Occur more frequently in older women
True False
True False
b. Is by aspiration of 3-4 blastomeres
True False
c. Is facilitated by using culture medium supplemented with calcium and magnesium
True False
d. Is undertaken at the 32 cell stage
True False
a. Female carriers of 14q21q Robertsonian translocations have a 50% risk of having a baby with
Down syndrome
True False
b. Male carriers of 14q21q Robertsonian translocations have a 2% risk of having a baby with
Down syndrome
True False
c. Female carriers of 21q21 Robertsonian translocation have a 100% risk of a live birth with Down
syndrome
True False
d. The risk of having a baby with Down syndrome as a result of a 14q21q translocation increases
with increasing maternal age
True False
True False
b. Results in the formation of two Barr bodies in 47XXX individuals
True False
c. Occurs at 15-16 days after conception
True False
d. May result in a female being affected by an X-linked recessive disorder
True False
Question 10: The following can be used for pre-implantation genetic diagnosis
True False
b. Polar body from the zygote
True False
c. Blastomeres from cleavage stage embryos
True False
d. Trophectoderm cells from the blastocyst
True False
True False
b. Result in a reduction of the total number of chromosomes to 45
True False
c. Involving chromosomes 13 and 14 are most common
True False
d. Do not increase the risk of miscarriage in carriers of balanced Robertsonian translocations
True False
True False
b. Cystic fibrosis - autosomal recessive
True False
c. Cystinuria ? autosomal dominant
True False
d. Androgen insensitivity syndrome ? autosomal recessive
True False
True False
b. Samples must be delivered to the lab within 12h for successful karyotype
True False
c. Cell division is arrested during prophase by the addition of colchicines
True False
d. Chromosomes are characteristically stained with haematoxylline and eosine
True False
a. Refers to the presence of variation in the DNA content of a particular chromosome in different
individuals
True False
b. Is caused by loss of small amounts of DNA during an individual?s life
True False
c. The X chromosome shows the greatest variation
True False
d. The Y chromosome shows the least variation
True False
True False
b. Results in the formation of the Barr body
True False
c. In famale carriers of a balanced X-autosome translocation, results in the preferential
inactivation of the abnormal X chromosome
True False
d. Results in the formation of two Barr bodies in 47XXY individuals
True False
HYPERCHOLESTEROLAEMIA (FAMILIAL) *****
• Autosomal dominant
• Onset in 30s - 40s with xanthelasma, xanthomata and corneal arcus and ischaemic heart disease
• Autosomal dominant
• Autosomal dominant
• Associated with lens subluxation, aortic aneurysm, arachnodactyly, long limbs and joint laxity
Facioscapulohumeral
• Autosomal dominant
• Autosomal dominant
• Correlation between the length of the repeats and severity of the disease
• The length of the repeat may change during transmission, altering the severity of the disease from
one generation to the next
• Neonatal disease does not occur if the father has the disease. With maternal disease, there is a
20% risk of neonatal death or severe neonatal hypotonia and mental handicap
• Clinical features include frontal balding, distal muscle and sterno-mastoid weakness, gonadal
atrophy in males, difficulty relaxing a clenched fist, cardiac conduction defects and retinopathy
• Pre-natal diagnosis by direct DNA analysis
OSTEOGENESIS IMPERFECTA
• Type I - autosomal dominant, associated with recurrent fractures, blue sclera, otosclerosis leading
to conduction deafness. Normal life span
• Type II - variable inheritance with a 3% recurrence risk - causes perinatal death with muntiple
fractures at birth
OTOSCLEROSIS
• vWF promotes platelet adhesion to sub-endothelium and binds and stalilises factor VIII
• Infection, stress, inflammation, physical exercise and recent surgery and pregnancy cause raised
vWF and factor VIII levels
You will be expected to know
• You will be required to know details of conditions which have effects on obstetric
or gynaecological care, for instance, inherited bleeding disorders.
Genetics :. Autosomal dominant conditions :. Module 2: 60 Random questions for MCQ Test
Question 1: Acute intermittent porphyria
True False
b. Can be precipitated by oestrogen administration
True False
c. Can be precipitated by sulphonamide administration
True False
d. Pre-natal diagnosis is possible by amniocentesis
True False
Question 2: Achondroplasia
True False
b. Is associated with a point mutation in the gene for fibroblast growth factor receptor 3
True False
c. Is associated with a normal IQ and life span
True False
d. Is associated with an increased risk of spinal cord compression
True False
True False
b. Is associated with nephritis
True False
c. Is associated with chronic renal failure
True False
d. Is associated with a normal IQ
True False
True False
b. Pre-natal diagnosis by amniocentesis is possible
True False
c. Pre-natal diagnosis by CVS is possible
True False
d. Fetal skin biopsy is required for pre-natal diagnosis
True False
True False
c. Type I ? recurrent fractures, blue sclera and conductive deafness
True False
d. Type II ? associated with perinatal death
True False
True False
b. Carries a normal life span
True False
c. Is associated with aortic aneurysms
True False
d. Is caused by a new mutation in 1% of cases
True False
True False
b. Patients typically improve following alcohol consumption
True False
c. Is caused by a mutation in the cytochrome P450 gene
True False
d. Family members can be screened by biochemical analysis
True False
True False
b. Is associated with increased platelet aggregation
True False
c. Is ssociated with increased platelet aggregation with ristocetin
True False
d. Causes prolonged bleeding time
True False
True False
b. Is associated with a normal life span
True False
c. Is particularly common in people of African origin
True False
d. Is associated with splenomegaly
True False
True False
b. There is a quantitative or a qualitative defect in von Willebrand factor
True False
c. Factor VIII concentration may be reduced
True False
d. Surgery is associated with increased von Willebrand factor concentration
True False
Question 11: The following are characteristic features of autosomal dominant inheritance
True False
b. Unaffected individuals cannot transmit the condition
True False
c. Males can transmit the condition to their sons
True False
d. If the mother is affected and the father is unaffected, there is a 1 in 4 chance of the off-spring
being affected
True False
True False
b. Is associated with a conjugated hyperbilirubinaemia
True False
c. Is associated with increased osmotic fragility of red cells
True False
d. Can be treated by spleenectomy
True False
Question 13: The following are characteristic features of autosomal dominant inheritance
True False
b. There is a vertical pedigree pattern
True False
c. There is a maternal age effect on new mutations
True False
d. Variable expressivity within a family
True False
True False
b. Typically presents between the ages of 30-50 years
True False
c. Is associated with psychiatric manifestations
True False
d. Pre-natal diagnosis is not possible
True False
True False
b. Frontal balding and proximal muscle weakness
True False
c. Difficulty opening a clenched fist
True False
d. Gonadal atrophy in males
True False
ALPHA-1 ANTI-TRYPSIN DEFICIENCY *****
• Autosomal recessive
• Carrier frequency 3% in Caucasians
• Z-allele is a point mutation which interferes with the
release of anti-trypsin from hepatocytes
• Diagnosis made by protease inhibitor activity assay or
DNA analysis (CVS or amnio)
• Associated with juvenile cirrhosis, emphysema
• Autosomal recessive
• 95% due to 21-hydroxylase deficiency
• Incidence 1:17,000 (UK), 1:500 Yupik Eskimos
Clinical *****
CYSTINURIA
• Autosomal recessive
• Defect in gene for transporter of cationic and neutral
amino acids (cystine, lysine, arginine and ornithine)
• Associated with recurrent urinary calculi. IQ is unaffected
FREIDREICH’S ATAXIA
• Autosomal recessive
• Commonest inherited cause of cerebellar ataxia
• Ataxia, pes cavus, loss of deep tendon reflexes and
extensor plantar response
• Wheelchair bound by age 45
• Pre-natal diagnosis possible by DNA analysis (CVS or
amniocentesis)
GALACTOSAEMIA *****
• Autosomal recessive
• Mutation in galactose-1-phosphate uridyl transferase
gene
Clinical Features
• Autosomal recessive
• Mutation in beta-galactosidase gene
• Type I (chronic adult type) common in Ashkenazi Jews
with carrier frequency of 1:10 and presents with bone pain
and splenomegaly
• Infantile form presents with progressive neurological
deterioration and hepato-splenomegaly
• Prenatal diagnosis possible by DNA analysis (CVS or
amniocentesis) or beta-galactosidase assay
HAEMOCHROMATOSIS *****
• Autosomal recessive
• Increased serum iron, ferritin, transferrin saturation and
increased iron in liver biopsy
• Long term complications include diabetes mellitus,
cardiomyopathy, arthropathy and cirrhosis
• Repeated venesection reduces iron overload
MUCOPOLYSACCHARIDOSES *****
PHENYLKETONURIA *****
• Autosomal recessive
• Deficiency of phenylalanine hydroxylase
• Promptly treated with a low phenylalanine diet is associated with
normal life span although some degree of learning disability may be
present
• After childhood (6-8years), the brain is less susceptible to the harmful
effects of high phenylalanine levels
• Risk of fetal structural abnormalities including microcephaly if
treatment is not re-introduced in an affected woman before conception
• Causes high blood and urine phenylalanine levels
• Neonatal screening using the Guthrie test
• Autosomal recessive
• Point mutation in beta-globin gene resulting in substitution of valine
for glutamic acid at position 6
• Fetal haemoglobin does not have a beta chain therefore fetal /
neonatal anaemia do not occur
• If both parents are carriers, 25% of off-springs will be normal, 25%
will have the disease and 50% will be carriers
• Severe chronic haemolytic anaemia with recurrent episodes of
infarction in spleen, lungs and bone. Increased susceptibility to
pneumococcal and salmonella infections
• Autosomal recessive
• Mutation in cholinesterase 1 gene resulting in cholinesterase
deficiency
• Affected patients are asymptomatic until exposed to suxamethonium
during induction of general anaesthesia
• Autosomal recessive
• Mutation in beta-N-acetylhexosaminidase A gene
• Highest frequency in Ashkenazi Jews with carrier frequency of 1:30
• 90% have cherry-red macular spot
• Pre-natal diagnosis by direct DNA analysis (CVS or amniocentesis)
or by assay of beta-N-acetylhexosaminidase A activity in chorionic villi or
amniocytes
• Death usually by the age of 3-4 years.
You will be expected to know
True False
b. Is most common in Eskimos
True False
c. Is associated with male precocious puberty
True False
d. Maternal administration of dexamethasone will prevent virilisation of an affected female fetus
True False
True False
b. Failure to thrive
True False
c. Normal IQ even in the absence of treatment
True False
d. Hepatomegaly
True False
Question 3: Cystinuria
True False
b. Is associated with learning disability
True False
c. Is associated with an increased risk of gall stones
True False
d. Is associated with increased urinary excretion of cystine, lysine, arginine and ornithine
True False
True False
b. Is always caused by a mutation in the delta-F508 gene
True False
c. Is associated with congenital absence of the vas in males
True False
d. Is associated with congenital absence of the fallopian tubes in females
True False
True False
c. Pre-natal diagnosis is not possible by CVS
True False
d. The sodium concentration is typically < 60mM in sweat
True False
True False
b. Can be diagnosed pre-natally by chorionic villus sampling
True False
c. Can be diagnosed pre-natally by amniocentesis
True False
d. Is associated with reduced IQ
True False
Question 7: Galactosaemia
True False
b. Is associated with premature ovarian failure
True False
c. Is treated by exclusion of milk products from the diet until adulthood and during pregnancy
True False
d. Causes learning disability if treatment is instituted after 1 month of age
True False
a. Glycosuria
True False
b. Galactosuria
True False
c. Cataract
True False
d. Neonatal jaundice
True False
True False
b. Shows an abnormal haemoglobin band on electrophoresis
True False
c. Is associated with increased levels of fetal haemoglobin in affected adults
True False
d. Causes neonatal anaemia
True False
Question 10: The following are characteristic features of Wilson disease (hepatolenticular
degeneration)
True False
b. Basal ganglia degeneration
True False
c. Psychiatric manifestations
True False
d. Kayser-Fleischer rings
True False
True False
b. Increased serum iron
True False
c. Decreased serum transferrin saturation
True False
d. Diabetes mellitus
True False
True False
b. Has a carrier frequency of 3% in Caucasians
True False
c. Pre-natal diagnosis by chorionic villus sampling is possible
True False
d. Pre-natal diagnosis cannot be performed using amniotic fluid
True False
Question 13: The following are characteristic features of autosomal recessive inheritance
True False
b. There is a vertical pedigree pattern
True False
c. Affected individuals are infertile
True False
d. All the off-spring of an affected individual will either have the condition or be carriers
True False
Question 14: The following are characteristic features of Wilson disease (hepatolenticular
degeneration)
True False
b. Increased hepatic copper deposition
True False
c. Onset in infancy
True False
d. Treatment with D-penicillamine
True False
Question 15: The following are characteristic features of autosomal recessive inheritance
True False
b. There is an increased risk in consanguineous marriages
True False
c. There is variable expressivity within a family
True False
d. There is variable penetrance within a pedigree
True False
ALPORT SYNDROME
• X-linked recessive *
• Mutation in androgen receptor gene
• Female phenotype, normal breast development, absent uterus
with blind-ending vagina; paucity of pubic and axillary hair *
• Testes found in abdomen or inguinal canal *
• Increased risk of gonadoblastoma *
• Infertility is universal
• Karyotype 46XY
• Risk of inguinal hernia increased *
FABRY DISEASE
• X-linked recessive
• Mutation in alpha galactosidase A gene resulting in alpha
galactosidase A deficiency in plasma, leucocytes and skin
fibroblasts
• Presents in childhood in affected males with limb pains and
skin lesions
• Pre-natal diagnosis possible by fetal sexing and DNA analysis
• X-linked recessive *
• Deficiency of erythrocyte glucose-6-phosphate
dehydrogenase
Clinical Features
• May be asymptomatic
• Neonatal jaundice
• Chronic haemolytic anaemia
• Haemolysis induced by eating fava beans, sulphonamides,
primaquine and infection
• Female carriers may suffer haemolytic crises
HAEMOPHILIA *****
LESCH-NYHAN SYNDROME
• X-linked recessive
• Deficiency in red cell hypoxanthine-guanine phosphoribosyl
transferase
• Onset in infancy with spasticity, learning disability and chorea-
athetosis
• Pre-natal diagnosis by direct DNA analysis
DUCHENNE *****
• X-linked recessive
• Null mutation resulting in absence of dystrophin on muscle
biopsy
• Onset in childhood (by age of 5) with proximal muscle
weakness, calf pseudo-hypertrophy; mild learning disability in
25%, majority wheelchair bound by age 12 with death in 20s.
BECKER *****
• X-linked recessive
• Reduced dystrophin on muscle biopsy
• Onset in late childhood, calf pseudo-hypertrophy. Wheelchair
bound by age 25, life-span may be normal - better prognosis
than Duchenne
• Pre-natal diagnosis for Duchenne / Becker muscular
dystrophy by direct DNA analysis (CVS / Amnio)
• Carriers have elevated serum creatinine and can be used for
screening
• In the absence of a family history, 2/3 of mothers of boys with
Duchenne / Becker muscular dystrophy will be carriers
Genetics :. X-linked conditions :. Module 4: 60 Random questions for MCQ Test
Question 1: Androgen insensitivity syndrome
True False
b. Is characterised by a female phenotype
True False
c. Is associated with secondary amenorrhoea
True False
d. Is characterised by a normal uterus and the presence of testes in the abdomen or inguinal
canal
True False
True False
b. Red-green colour blindness is an autosomal recessive disorder
True False
c. Red-green colour defects affects 0.1% of male Caucasians
True False
d. Red-green colour blindness is more common in Africans
True False
True False
b. Becker muscular dystrophy is an autosomal recessive disorder
True False
c. Duchenne muscular dystrophy is associated with learning disability
True False
d. Becker muscular dystrophy carries a worse prognosis than Duchenne muscular dystrophy
True False
True False
b. Haemophilia B - factor XI deficiency
True False
c. Haemophilia A - X-linked recessive
True False
d. Haemophilia B - autosomal recessive
True False
True False
b. Vertical pedigree pattern
True False
c. Affected males transmit the trait to their daughters
True False
d. Affected males transmit the trait to their sons
True False
True False
b. Dystrophin is not detectable on muscle biopsy in Becker muscular dystrophy
True False
c. Pre-natal diagnosis is possible in Duchenne and Becker muscular dystrophy by direct DNA
analysis of chorionic villi
True False
d. If there is no family history of muscular dystrophy, 10% of mothers of boys with the disease will
be carriers
True False
True False
b. There is normal pubic and axillary hair development
True False
c. Infertility is universal
True False
d. Is associated with an increased risk of inguinal hernia
True False
True False
b. Carriers of muscular dystrophy have normal serum creatinine concentrations
True False
c. 10% of children with Duchenne muscular dystrophy will be wheelchair bound by the age of 12
True False
d. Duchenne muscular dystrophy typically presents with distal muscle weakness
True False
True False
c. Haemolysis induced by sulphonamides
True False
d. Haemolysis induced by infection
True False
True False
b. Pre-natal diagnosis can be performed by amniocentesis
True False
c. There is a 5-10% risk of chronic renal failure in female carriers
True False
d. There is a 1% risk of chronic renal failure in males
True False
True False
b. Haemophilia A - prenatal diagnosis by CVS is contraindicated
True False
c. Haemophilia B - 50% risk of male fetus being affected if the mother is a carrier
True False
d. Haemophilia A - 50% risk of male fetus being affected if the father has the disease
True False
True False
b. Is an autosomal dominant condition
True False
c. Is associated with nephritis and proteinuria
True False
d. Is associated with sensori-neural deafness
True False
Question 13: A female may be affected by Duchenne muscular dystrophy under the following
circumstances
a. Atypical lyonisation
True False
b. Her father is affected and her mother is a carrier
True False
c. Her father has the disease and there is a new mutation in the maternally derived X
chromosome
True False
d. She carrier an X-autosome translocation
True False
Question 14: The following are characteristic features of X-linked recessive inheritance
True False
b. Knight?s move pedigree pattern
True False
c. A woman with a affected child is an obligate carrier
True False
d. A woman with an affected son and an affected brother is an obligate carrier
True False
True False
b. Females are affected less often than males
True False
c. All daughters of an affected father are affected
True False
d. All sons of an affected woman will be affected
True False
PRADER-WILLI SYNDROME
•
Characterised by 15q deletion in paternally derived
chromosome
•
The majority of deletions occur de-novo but 2% are associated
with parental structural chromosomal anomaly
•
In 25% of cases, there is no deletion but maternal
uniparental disomy of chromosome 15 with consequent lack of
critical paternally derived genes
CLINICAL FEATURES
ANGELMAN SYNDROME
CLINICAL FEATURES
Trisomy 21
95% due to non-dysjunction in the FIRST meiotic division;
1-2% mosaics, 3% unbalanced Robertsonian translocation
Extra chromosome derived from the mother in 80-85% of
cases
Associated with increasing maternal age
Associated with low AFP, low unconjugated oestriol and
increased HCG in maternal serum and increased nuchal
thickening
1) GENERAL
Neonatal hypotonia
Learning disability
Short stature
Increased risk of Alzheimer's, hypothyroidism, acute
leukaemia, epilepsy and atlanto-axial instability
2) CRANIO-FACIAL
Brushfield spots
Brachycephaly
Epicanthic folds
Protruding tongue
Upward sloping palpebral fissures
Strabismus
Nystagmus; congenital cataract
3) LIMBS
• 47,XXY
• Incidence 1:1000 males; risk increases with increased
maternal age
• Extra X chromosome is maternal in 50-60% of cases;
recurrence risk close to population risk
• Short stature with broad chest and widely spaced nipples; low
hair line with webbed neck
• Wide carrying angle and short 4th metacarpals and hypoplasia
of the nails
• Peripheral lymphoedema
Clinical Features
• IUGR
TRIPLOIDY *****
True False
b. Is typically associated with secondary amenorrhoea
True False
c. Has a 45XX karyotype
True False
d. Is associated with widely spaced nipples
True False
a. 95% of cases are due to non-dysjunction during the second meiotic division
True False
b. The extra chromosome is maternally derived in 99% of cases
True False
c. Mosaicism accounts for 5% of cases
True False
d. The recurrence risk in a 20 year old with one baby with Down syndrome is 5%
True False
Question 3: The following malformations are typically associated with Down syndrome
True False
b. Coarctation of the aorta
True False
c. Duodenal atresia
True False
d. Neural tube defect
True False
True False
b. Is associated with anosmia
True False
c. Testosterone levels are within the normal adult male range
True False
d. Is associated with small testicles
True False
a. Abnormal ECG
True False
b. Poor speech
True False
c. Inappropriate paroxysms of laughter
True False
d. Obesity
True False
True False
b. 1% are mosaics
True False
c. The extra X chromosome is always maternal in origin
True False
d. There is a 1% recurrence risk
True False
Question 7: Trisomy 18
True False
b. Is commoner by males at birth
True False
c. Is associated with low maternal serum AFP
True False
d. Is associated with low maternal serum HCG
True False
True False
b. Paternal uniparental disomy of chromosome 15
True False
c. Normal IQ
True False
d. Neonatal hypotonia
True False
True False
b. Is associated with increased maternal serum HCG
True False
c. Is associated with increased maternal serum unconjugated oestriol
True False
d. Is associated with decreased nuchal thickening
True False
True False
b. The fragile site is induced by thymidine deprivation in culture
True False
c. The fragile site is induced by deoxycytidine deprivation in culture
True False
d. There is a reduction in the length of the CGG trinucleotide repeat at Xq27.3
True False
a. Failure to thrive
True False
b. Learning disability
True False
c. Triploidy
True False
d. Deletion in paternally derived chromosome 15q
True False
Question 12: The following cranio-facial abnormalities are typical of Down syndrome
a. Brachycephaly
True False
b. Epicanthic folds
True False
c. Protruding tongue
True False
d. Small low set ears
True False
True False
b. Occurs in 2% of conceptions
True False
c. Is associated with a large placenta
True False
d. The extra chromosomes are maternally derived in 95% of cases
True False
True False
b. Is associated with a 10% survival to 1 year of age
True False
c. 95% is associated with paternal non-disjunction
True False
d. Is typically associated with atrio-ventricular canal defects
True False
True False
b. With 45X karyotype is associated with an increased risk of ovarian cancer in the streak ovaries
True False
c. Life span is normal
True False
d. The uterus is typically absent
True False
1
9 In an X-linked pedigree: √
A None of the sons of an affected male will be affected. T
B Half of the daughters of an affected male will not carry the gene. F
C Half of the sons of carrier females will be affected. T
D Females are never affected. F
E All the daughters of a carrier female will themselves be carriers. F
Comment:
One of the X chromosomes in the female undergoes inactivation and
this may be the maternal or paternal X chromosome. The Barr body
seen in all nucleated cells is the inactivated X chromosome and one is
seen with the XX genotype. Two Barr bodies are seen with the XXX
genotype. Triple X syndrome is associated with a below average
intelligence.
About 5-15% of PMNs have drum stick of chromatin.
20 In the neonate, the appearance of the external genitalia may not
correspond with the genotype in the presence:
A Adrenogenital syndrome. T
B Testicular feminization syndrome. T
C Renal agenesis (potter's syndrome). F
D Trisomy21. F
E Severe hypospadias. T
21 In the human:
A Haploid cells contain homologous pairs of chromosomes. F
B Polyploidy cells contain extra sets of chromosomes. T
C Monosomic cells contain an extra chromosome. F
D Haploid cells contain 22 autosomes. T
6
23 Mitochondrial DNA: √
A Is located in the nucleus. F
B Inheritance is patrilineal. F
C Is present in two copies per cell. F
D Mutation causes cystic fibrosis. F
E Is involved in the control of oxidative phosphorylation. T
Comment:
The DNA is located in the mitochondria.
It has 10 copies of DNA.
Inheritance is matrilineal.
24 In DNA: √
A Acodon is a sequence of three bases. T
B All codons have an identified function. F
C There is a greater variety of amino acids than there are different F
codons.
D Replication can be initiated at several different points along a T
chromosome.
E Complementary pairing precedes messenger RNA synthesis. T
Comment:
A codon is a sequence of three base pairs with a further sequence of
opposite base pairs on tRNA representing the anticodon. These codons
code for all amino acids but also code for extra or nonsense sequences
which may encode termination sequences.
25 Concerning the genetic control of protein synthesis: √
A Mature messenger RNA contains introns. F
B A codon has 3-base sequences. T
C Each amino acid has a single codon. F
D Transfer RNA has anticodon recognition sites. T
E Each transfer RNA carries a specific amino acid. T
1)C-reactive protein
1)Fibrinogen
2)Fibronectin
3)Ceruloplasmin
4)Haptoglobin
5)Angiotensin
7)Alpha-1 antichymotrypsin
C-REACTIVE PROTEIN
• Results in activation of complement via the classical pathway. This results in C3b deposition on
microbes and opsonisation
CYTOKINES
• Low molecular weight secreted proteins that mediate immunity, cell migration, growth, differentiation
and repair
• Both mRNA and proteins have a short half life, enabling tight regulation
• Effects mediated by cell surface receptors which undergo ligand-induced sub-unit association to
enable signal transduction
• Cytokines are pleiotropic - exhibit multiple effects on a variety of cell types with considerable overlap
and redundancy with respect to individual functions
CAUSES:
• Fever
• Apoptosis
INTERFERON-GAMMA
• Activates macrophages, inhibits viral replication and stimulates some antibody responses
INTERLEUKIN-12
• Stimulates the differentiation of nave T-cells into the effector cells of the adaptive immune system
INTERLEUKIN-1
• Induces fever
• Phagocytic cells - dominant white cell in the blood stream, making up 40-75% of total leukocyte
count *
• Non-dividing
• Granules do not stain with either acidic or basic dyes (hence neutrophils)
• Count is increased by: Bacterial infections, trauma (including surgery), infarction, burns,
haemorrhage, disseminated malignancy and corticosteroid therapy
• Count is decreased by: viral infections, TB, brucellosis, typhoid, drugs such as carbimazole
and sulphonamides, severe septicaemia, hyper-splenism, B12 and folate deficiency
MONOCYTES *****
• Differentiate into macrophages, including Kupffer cells and microglia within connective tissue
MACROPHAGES *****
• Present in all connective tissue but are particularly concentrated in the lungs forming alveolar
macrophages, liver (Kupffer cells), spleen, kidneys (glomerular mesangial cells), brain
(microglial cells) and bone (osteoclasts)*
• Long-lived in tissues
• Activated macrophages generate reactive oxygen species such as superoxide, hydroxyl radical
and nitric oxide which are essential for killing microbes
• Fibroblast growth factor, angiogenic factors and metalloproteinases are secreted and play a
role in the remodelling of infected tissues
• NK cells a group of cytolytic lymphocytes, distinct from B-lymphocytes and T-lymphocytes, that
participate in both innate immunity and adaptive immunity*
• Lack B-cell receptors (surface immunoglobulins) and T-cell receptors (TCR / CD3) *
• Specialized to kill certain types of target cells, especially cells infected with virus or malignant
cells *
Features of NK Cells
• NK cells do not express surface immunoglobulins or TCR/CD3 on their surface. The surface
markers that best characterize NK cells are CD2+,CD3-, CD4-, and CD56+ *
• NK receptors are polymorphic so that the repertoire of NK receptors differs from person to
person.
• The first NK cell receptor, called the killer-activating receptor recognises stress-induced
molecules. This interaction sends a positive signal which enables the NK cell to kill the cell to
which it has bound unless the second receptor cancels that signal.
• This second receptor, called the killer-inhibitory receptor (KIR), recognises MHC-I molecules
which are usually present on all nucleated human cells.
• If MHC-I molecules are expressed on the cell, the killer-inhibitory receptor sends a negative
signal that overrides the kill signal and prevents the NK cell from killing that cell
• This ensures that NK cells are not activated by normal host cells
• Viruses often suppress class I MHC expression in cells they infect, the virus-infected cell
becomes susceptible to killing by NK cells.
• Malignant cells have reduced or no class I MHC expression and are susceptible to killing by NK
cells.
• NK cells kill cells to which antibody molecules have attached through a process
called antibody-dependent cytotoxicity
• The killing is done by the exocytosis of granules containing perforin and granzymes.
• Pre-programmed to recognise their targets and have no need to develop into a clone of
identical cells.
• Mast cells have large basophilic granules that contain histamine and other substances that
induce vasodilatation, increase vascular permeability, increase secretions and smooth muscle
constriction.
• Excessive activation of mast cells leads to symptoms that characterise allergic diseases such
as hay fever and asthma.
• Generalised mast cell activation results in widespread blood vessel dilation; this can result in
a catastrophic drop in blood pressure - an effect termed anaphylactic shock.
• Of the phagocytes only macrophages and Langerhans cells retain an intact nucleus after
leaving the marrow and have the potential to divide in the periphery.
• Chromatin (chromosomal material) is lost both from eosinophils and neutrophils during the end
stages of their maturation in the marrow.
• This is reflected in the polymorphic nuclei of these cells; they are sometimes known as
polymorphs.
• Both eosinophils and neutrophils have a short life-span after leaving the marrow (see table
below)
All three main types of phagocyte have the capacity to kill microbes they ingest or
adhere to.
• Liver macrophages (Kupffer cells) are perfused principally by the portal blood supply, which
drains the intestines and the spleen.
• Splenic macrophages play a major role in taking up and destroying effete blood cells.
• Maternal deciduas infiltrated with macrophages and NK cells especially in the first trimester
• Increased number of monocytes and granulocytes in peripheral maternal blood from the first
trimester
• Circulating monocytes and granulocytes are activated with respect to some functions
• Increased concentration of acute phase proteins and activation of the clotting system
• Range of circulating and membrane-associated proteins that are important for host defence
• Following cleavage of a component, the larger product has the suffix 'b' and the smaller 'a'
• The alternative pathway is activated when complement proteins are activated on microbial
surfaces - this is part of the innate immune system and cannot be controlled as there are no
complement-regulatory proteins on microbes *
• The classical pathway is activated by the binding of antibodies to microbes or other antigens -
part of the adaptive immune system *
• The lectin pathway is activated by the binding of a plasma protein (mannose-binding lectin) to
surface glycoproteins of microbes. Mannose-binding lectin activates components of the
classical pathway but is a component of the innate immune system as it is activated in the
absence of antibodies *
HYPERACUTE REJECTION
• Antibody mediated response caused by pre-existing antibodies that may have developed as a
result of previous blood transfusion - therefore more likely to occur in those with previous
transfusion
• Corneal and cartilage transplants are not rejected as these are avascular structures and
therefore do not sensitize the recipient
ACUTE REJECTION
• Early acute rejection is a cell mediated hypersensitivity reaction (T-cell) although antibody
mediated hypersensitivity also contributes
• Occurs over several months / years and manifests as a gradual loss of graft function
• T-cell mediated response with the production of cytokines which induce fibrosis and
proliferation of vascular smooth muscle
GRAFT VERSUS HOST REACTION
• Occurs when competent T-cells are transplanted from a donor to a recipient who is unable to
reject them. The cells survive, recognise the host's antigens and mount an immunological
reaction
• May follow bone marrow transplant or occur as a result of T-cells present in transplanted
organs
The reaction is greater the greater the HLA difference between the host and the donor.
May be fatal
HYPERSENSITIVITY REACTIONS
• Rapid IgE and mast cell dependent vascular and smooth muscle reaction that is usually
followed by an inflammatory reaction in an individual who has been previously exposed to an
antigen (sensitized) *
• Antigen binds to IgE on mast cells, cross-linking receptors and inducing mast cell
degranulation *
• Released mast cell granules contain histamine, heparin, neutral proteases and cytokines
typical of TH2 responses - IL-3 and IL-4 *
• Cyclo-oxygenase and lipoxygenase are also activated with the production of vasodilator
prostaglandins, leukotrienes and thromboxanes *
• The result is increased capillary permeability, smooth muscle contraction and this manifests as
wheezing, oedema, hypotension - this is the acute phase and occurs within minutes *
• The latent phase peaks after 3-5 hours and is caused by cytokine mediated inflammatory
infiltration by neutrophils and eosinophils - this is responsible for tissue damage that occurs
after repeated episodes of immediate hypersensitivity *
• Typical disease processes include asthma, hay fever, drug and insect bite induced
anaphylaxis, penicillin allergy, food allergy, atopic dermatitis *
• Disorders include *
6) Pernicious anaemia
• These complexes activate macrophages, activate complement and cause the extracellular
release of neutrophil granules and tissue damage *
3) Post-streptococcal glomerulonephritis
4) Jarisch-Herxheimer reaction
• Occurs in allergic reactions to bacteria, fungi and viruses, contact dermatitis and in the
rejection of transplanted tissues *
• Typically occurs in the Mantoux reaction to tuberculin injected in the skin of a sensitized
individual - characterised by erythema and induration *
• Reaction occurs after several hours and peaks 24-48h after contact *
• The early phase is characterised by a perivascular cuffing with mononuclear cells, and then
polymorphs which later leave. The late phase is characterised by a lymphocyte and monocyte-
macrophage infiltration *
• T-lymphocyte dependent, and TH1 dependent in most cases, resulting in activation of
macrophages. TH2 responses do however occur, for instance in the hepatic lesions in
schistosomiasis *
• Antigen interacts with primed T-cells with tissue damage resulting from inappropriate cell
mediated immune reactions
• The chronic inflammatory response leads to the formation of granulomas, which may be
caseating in the case of TB *
Occurs in Crohn's disease, psoriasis, celiac disease, TB, leprosy, contact dermatitis,
tissue damage following measles and herpes infection; schistosomiasis *
• B-lymphocyte maturation occurs in the bone marrow while T-lymphocyte maturation occurs in
the thymus
• The proliferation of pro-B and pro-T cells is stimulated by interleukin-7 secreted by the bone
marrow or thymus
• Only recognises peptide antigens displayed by MHC molecules. Does not recognise lipid,
polysaccharide or nucleic acid antigens *
• Each receptor has an alpha and a beta chain each with a variable and a constant domain
homologous to those on immunoglobulins
LYMPHOCYTES *****
• Following stimulation by antigen, some lymphocytes differentiate into memory cells which are
capable of mounting a rapid response if the same antigen is later encountered
• Most lymphocytes are located in secondary lymphoid tissues - lymph nodes, the white pulp of
the spleen, the gut- and bronchial-associated lymphoid tissues.
• The part of the B cell receptor that binds antigen is surface immunoglobulin*
• Subsequent B cell proliferation and maturation generates plasma cells that secrete this
immunoglobulin *
• In contrast to B cell receptors, T cell receptors do not bind free antigen. The antigen must be
processed into small peptides by antigen presenting cells and these antigen derived peptides
are displayed on the antigen presenting cell surface in the clefts of molecules called major
histocompatibility molecules (MHC) *
B-LYMPHOCYTES *****
• Mature in the bone marrow. Develop into antibody producing plasma cells. Only immune cells
capable of antibody production *
• Plasma cells migrate to the bone marrow where they produce small quantities of antibodies
for long periods of time after the initial infection has been cleared
• The bound antigen molecules are engulfed into the B cell by receptor-mediated
endocytosis. *
• The antigen is digested into fragments which are then displayed at the cell surface nestled
inside a class II histocompatibility molecule. *
• Helper T cells with complementary TCRs bind the B cell and secretelymphokines that *
1) Stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into
aclone of cells with identical BCRs;
• Can only recognise peptide antigens that are bound to MHC molecules on specialised antigen-
presenting cells - MHC-restricted *
• CD4 positive T-cells are helper T-cells - help B cells produce antibodies and help phagocytes
destroy ingested organisms *
• CD8 positive T-cells are cytotoxic T-cells - capable of killing host cells infected with intracellular
organisms *
• Na-ve T-cells have antigen receptors but do not perform the functions required to eliminate the
antigen
CD8+ T cells
• CD8+ T cells bind that are part of class I histocompatibility molecules. Almost all the cells of
the body express class I molecules
• The best understood CD8+ T cells are cytotoxic T lymphocytes - secrete molecules that
destroy the cell to which they have bound.
• The role of the CD8+ T cells is to monitor all the cells of the body, ready to destroy any that
express foreign antigen fragments in their class I molecules.
CD4+ T cells
• CD4+ T cells bind epitopes that are part of class II histocompatibility molecules. Only
specialized antigen-presenting cells express class II molecules
• Essential for both the cell mediated and antibody-mediated branches of the immune system
• Bind to antigen presented by antigen-presenting cells and releaselymphokines that attract
other cells to the area.
• All nucleated cells can present antigens derived from microbes in the cytoplasm to cytotoxic T-
cells *
• Professional antigen-presenting cells include dendritic cells (Langerhans cells are epidermal
dendritic cells) and macrophages *
Langerhans cells
• This activation process induces Langerhans cells to migrate to secondary lymphoid tissues
where they present to T lymphocytes antigen derived peptide/MHC complexes.
• Lymph drains from the efferent lymphatics into the sub-capsular sinus and then through the
medullary sinuses into the efferent lymph vessels
• B-cells are concentrated in the cortex where they form follicles. Un-stimulated B-cells form
primary follicles while secondary follicles are formed following antigenic stimulation. Secondary
follicles have a germinal centre which is the site of B-cell maturation and the generation of B-
cell memory
• Naive T-cells leave the circulation to enter the lymph nodes through specialised post-capillary
venules called high endothelial venules
SPLEEN *****
• The red pulp is the red cell area - the spleenic capillaries are very porous and red cells leave
the capillaries to enter the red pulp. They then squeeze through the trabeculae which are lined
by a vast number of macrophages to re-enter the circulation at the venous end
• The white pulp contains follicles (B-cell area) and peri-arteriolar lymphoid sheaths (T-cell area)
• Old red cells and platelets are removed from the circulation in the spleen
Distribution
Cell type
Basophils /
Mast cells
Neutrophils
0.04-0.4x109/l 14-18 hr in blood blood and tissues
Eosinophils
Monocytes/
macrophages
5-14 days Mostly in tissues and
T zones of secondary
lymphoid tissues
Langerhans
cells
NK cells
T
lymphocytes
• The use of immunoglobulins to treat or prevent disease. Antibodies may be from human or
animal sources or may be genetically engineered
• Associated with serum sickness especially when antibodies are from an animal source
3) Hepatitis B
• Maternal IgG is actively transported by the placenta into the fetus. IgA is not taken up by the
placenta *
• Secreted IgA in breast milk is not absorbed but confers mucosal immunity in the GI tract *
VACCINATION *****
Types of Vaccines
• Killed organisms
• Live-attenuated organisms - replicate in the host. Provide a larger 'dose' and have the
advantage of inducing immunity at the natural site of infection
• Sub-unit vaccines - make use of the most antigenic subunit of the organism. These can be
produced by genetic engineering
Live Attenuated
• BCG - tuberculosis
Inactivated
• Cholera vaccine
• Pertussis vaccine
• Typhoid vaccine
Sub-unit
• H. influenzae
• N. meningitides
• S. pneumoniae
Toxoid
• Tetanus
• Diphtheria
VIRUSES
Live Attenuated
• Polio (Sabin)
• Adenovirus
• Yellow fever
Inactivated
• Polio (Salk)
• Influenza
• Rabies
• Hepatitis A
Sub-unit
• Hepatitis B
• Influenza
• Made up of membrane bound proteins on antigen presenting cells that display peptide antigens
for recognition by T-cells *
• MHC genes are highly polymorphic - there are many different alleles present in different
individuals. No two individuals in an outbred population have identical MHC genes or
molecules (except identical twins) *
• There are two sets of highly polymorphic HLA genes called class I and class II genes
• The MHC also contains several non-polymorphic genes, some involved in antigen presentation
and others with unknown functions
• Class I molecules are expressed by all nucleated cells while class II molecules are expressed
by professional antigen-presenting cells only (dendritic cells, macrophages and B-
lymphocytes) *
• Each person inherits one set from each parent, therefore each cell can express 6 different
class I molecules *
• CD8 positive T cells can therefore only respond to peptide antigens displayed by class I MHC
molecules
• Each person inherits one set from each parent, therefore each cell can express 6 different
class II molecules *
• The peptide binding site for class II molecules can bind peptides with 10-30 amino acids
• The beta2 domain on the beta chain of class II molecules is invariant and contains the binding
site for the T-cell receptor CD4
• CD4 positive cells can therefore only recognise peptide antigens displayed by MHC class II
molecules
POLYMORPHONUCLEAR NEUTROPHILS *****
• Phagocytic cells - dominant white cell in the blood stream, making up 40-75% of total leukocyte
count
• Non-dividing
• Granules do not stain with either acidic or basic dyes (hence neutrophils)
• Count is increased by: Bacterial infections, trauma (including surgery), infarction, burns,
haemorrhage, disseminated malignancy and corticosteroid therapy
• Count is decreased by: viral infections, TB, brucellosis, typhoid, drugs such as carbimazole
and sulphonamides, severe septicaemia, hyper-splenism, B12 and folate deficiency
MONOCYTES *****
• Differentiate into macrophages, including Kupffer cells and microglia within connective tissue
MACROPHAGES *****
• Present in all connective tissue but are particularly concentrated in the lungs forming alveolar
macrophages, liver (Kupffer cells), spleen, kidneys (glomerular mesangial cells), brain
(microglial cells) and bone (osteoclasts)
• Long-lived in tissues
• Activated macrophages generate reactive oxygen species such as superoxide, hydroxyl radical
and nitric oxide which are essential for killing microbes
• Fibroblast growth factor, angiogenic factors and metalloproteinases are secreted and play a
role in the remodelling of infected tissues
• NK cells a group of cytolytic lymphocytes, distinct from B-lymphocytes and T-lymphocytes, that
participate in both innate immunity and adaptive immunity*
• Lack B-cell receptors (surface immunoglobulins) and T-cell receptors (TCR / CD3) *
• Specialized to kill certain types of target cells, especially cells infected with virus or malignant
cells *
Features of NK Cells
• NK cells do not express surface immunoglobulins or TCR/CD3 on their surface. The surface
markers that best characterize NK cells are CD2+,CD3-, CD4-, and CD56+ *
• NK receptors are polymorphic so that the repertoire of NK receptors differs from person to
person.
• The first NK cell receptor, called the killer-activating receptor recognises stress-induced
molecules. This interaction sends a positive signal which enables the NK cell to kill the cell to
which it has bound unless the second receptor cancels that signal.
• This second receptor, called the killer-inhibitory receptor (KIR), recognises MHC-I molecules
which are usually present on all nucleated human cells.
• If MHC-I molecules are expressed on the cell, the killer-inhibitory receptor sends a negative
signal that overrides the kill signal and prevents the NK cell from killing that cell
• This ensures that NK cells are not activated by normal host cells
• Viruses often suppress class I MHC expression in cells they infect; the virus-infected cell
becomes susceptible to killing by NK cells.
• Malignant cells have reduced or no class I MHC expression and are susceptible to killing by NK
cells.
• NK cells kill cells to which antibody molecules have attached through a process
called antibody-dependent cytotoxicity
• The killing is done by the exocytosis of granules containing perforin and granzymes.
• Pre-programmed to recognise their targets and have no need to develop into a clone of
identical cells.
NKT Cells
• T cells with an αβ TCR. However, they also express some of the cell-surface molecules of NK
cells - hence their name.
• Differ from most T cells in the sharply limited diversity of their αβ TCRs and these respond to
glycolipid antigens presented by a cell-surface molecule designated CD1d (rather than to
peptide antigens presented by MHC molecules).
• Maternal deciduas infiltrated with macrophages and NK cells especially in the first trimester
• Increased number of monocytes and granulocytes in peripheral maternal blood from the first
trimester
• Circulating monocytes and granulocytes are activated with respect to some functions
• Increased concentration of acute phase proteins and activation of the clotting system
• Phagocytes have a range of mechanisms by which microbes are killed once within the cell.
These can be divided into oxygen-dependent and independent mechanisms
• OXYGEN DEPENDENT MECHANISMS - mainly involve the generation of highly reactive free
radicals:
• Hydroxyl radical
• Range of circulating and membrane-associated proteins that are important for host defence
• Following cleavage of a component, the larger product has the suffix 'b' and the smaller 'a'
• The alternative pathway is activated when complement proteins are activated on microbial
surfaces - this is part of the innate immune system and cannot be controlled as there are no
complement-regulatory proteins on microbes *
• The classical pathway is activated by the binding of antibodies to microbes or other antigens -
part of the adaptive immune system *
• The lectin pathway is activated by the binding of a plasma protein (mannose-binding lectin) to
surface glycoproteins of microbes. Mannose-binding lectin activates components of the
classical pathway but is a component of the innate immune system as it is activated in the
absence of antibodies *
True False
b. Recognise virally infected cells
True False
c. Make up 50% of lymphocytes
True False
d. Express immunoglobulins
True False
Question 2: The following chemicals are produced by phagocytes as part of the killing
mechanism
a. Hydrogen peroxide
True False
b. Superoxide dismutase
True False
c. Superoxide radical
True False
d. Hydroxyl radical
True False
True False
b. The lectin pathway is activated by the binding of mannose-binding lectin to the surface
glycoprotein on microbes
True False
c. Phagocytes express receptors for C3b
True False
d. C3b causes opsonisation of bacteria
True False
Question 4: Macrophages
True False
b. Are present in the circulation
True False
c. Are multinucleated cells
True False
d. Are concentrated in the lungs
True False
True False
c. Count is increased in vitamin B12 deficiency
True False
d. Count is increased in disseminated malignancy
True False
True False
b. Are peroxidase positive
True False
c. Are alkaline phosphatase positive
True False
d. Contain glycogen
True False
a. By convention, on cleavage of any component, the larger product is given the suffix ?a?
True False
b. The alternative pathway is a component of the innate immune system
True False
c. The alternative pathway is activated following antibody binding to microbes
True False
d. The alternative pathway can be controlled by complement regulatory proteins
True False
Question 8: Cytokines
True False
b. Have a short half life
True False
c. Act via receptors located within the cell nucleus
True False
d. Have multiple effects on a variety of cell types
True False
Question 9: The following chemicals are produced by phagocytes as part of the killing
mechanism
a. Nitric oxide
True False
b. Peroxynitrite
True False
c. Lysozyme
True False
d. Lactoferrin
True False
True False
b. Stain with basic dyes
True False
c. Divide by mitosis within the circulation
True False
d. Are multi-nucleated
True False
a. Is secreted by macrophages
True False
b. Is secreted by NK cells
True False
c. Activates macrophages
True False
d. Inhibits viral replication
True False
a. Secrete perforin
True False
b. Secrete interferon-gamma
True False
c. Can be activated by uninfected normal host cells
True False
d. Are activated by MHC-negative virally infected cells
True False
Question 13: The following mechanisms are used by the bacteria described to escape
destruction by the innate immune system
True False
b. Staphylococci ? capsular polysaccharide inhibits phagocytosis
True False
c. Neisseria meningitides ? resistance to complement activation
True False
d. Pseudomonas ? resistance to anti-microbial action of peptide antibiotics
True False
True False
b. Insulin-like growth factor
True False
c. Fibrinogen
True False
d. Ceruloplasmin
True False
True False
b. Is a dimer
True False
c. Binding to microbes is calcium-independent
True False
d. Binding to microbes activates complement via the alternative pathway
Question 1: Plasma cells
True False
b. Are characteristic of acute infection
True False
c. Are phagocytic
True False
d. Synthesise antibodies
True False
Question 2: IgM
True False
b. Binds to mast cells
True False
c. Is synthesised by plasma cells
True False
d. Is smaller than IgE
True False
True False
b. Are composed of humal leukocyte antigen genes
True False
c. Will be identical in dizygotic twins
True False
d. Code for blood group antigens
True False
True False
b. The 4 classes of IgG all cross the placenta readily
True False
c. The concentration of IgG in fetal blood at term is 10x that in maternal blood
True False
d. IgM cannot be produced by the fetus
True False
True False
b. Express the T-cell receptor on their surface
True False
c. Express immunoglobulins on their surface
True False
d. Are CD 56 positive
True False
Question 6: Antibodies
True False
b. Have an average molecular weight of 100kDa
True False
c. Of the Rhesus type are genetically transmitted
True False
d. Are produced by ribosomes of plasma cells
True False
True False
b. There is degranulation of mast cells
True False
c. Complement is required
True False
d. Histamine release occurs
True False
Question 8: T-lymphocytes
True False
b. Are involved in both cell mediated and humoral immune responses
True False
c. Are phagocytic
True False
d. Produce antibodies
True False
a. Opsonisation
True False
b. Cell membrane lysis
True False
c. Participation in the blood coagulation system
True False
d. Promotion of sperm motility
True False
True False
b. Have a life-span of about 30 days
True False
c. Do not participate in cell mediated immunity
True False
d. Can differentiate into plasma cells
True False
True False
b. The IgA concentration in cord blood is higher than in maternal blood
True False
c. IgE readily crosses the placenta
True False
d. Fetal IgM is monomeric
True False
True False
b. Contains J chains
True False
c. Is a dimmer in external secretions
True False
d. Contains an additional peptide produced by epithelial cells
True False
True False
b. Do not produce antibodies
True False
c. Play a role in delayed hypersensitivity
True False
d. Produce IgE
True False
True False
b. Increased vascular permeability
True False
c. Micro-thrombus formation
True False
d. Involvement of IgE antibodies
True False
True False
b. Release histamine on degranulation
True False
c. Contain heparin
True False
d. Have a specific affinity for IgA antibodies
True False
IMMUNOGLOBULINS *****
• Each light chain is attached to one heavy chain, and the heavy chains
are attached to each other by disulfide bonds
• Each light chain has one variable and one constant domain
• Each heavy chain has one variable and 3-4 constant domains
• The fragment of the antibody containing the whole of the light chain
attached to the variable and the first constant domain of the heavy
chain is the Fab region (Fragment antigen binding)
• The hinge region is located between the Fab and Fc regions which is
flexible and enables the two Fab regions to move and bind epitopes
that are separated by a variable distance
• Each antibody molecule therefore has two Fab (two antigen binding
sites) and one Fc fragment
• There are two different types of light chain - kappa and lambda
• There are five different types of heavy chain - mu (IgM), delta (IgD),
gamma (IgG), epsilon (IgE) and alpha (IgA) *
• Most fetal liver cells are pre-B but mature B-cells are also present.
Functional assays and transplantation experiments indicate that these
B-cells are functional and can transfer immunologic memory *
IgA *****
• Two subtypes (1&2), produced by epithelial plasma cells and dimerises
intracellularly - 4 antigen binding sites.
• Does not cross the placenta and does not sensitize mast cells *
IgD *****
IgE *****
IgG *****
IgM *****
• Does not cross the placenta - the presence of IgM in fetal blood
indicates fetal infection and fetal antibody production *
ANTIGEN RECOGNITION BY B-LYMPHOCYTES *****
• Antigens are recognised in their native conformation with no requirement for processing or
presentation by specialised antigen presenting cells
• Peptide and non-peptide antigens (including lipids, polysaccharides, nucleic acids are
recognised *
• The initial response to antigen is called the primary response, has a latent period of 5-10
days and is characterised by the production of small amounts of mainly IgM. *
• T-cell dependent responses are induced by protein antigens and the secondary response
shows affinity maturation (production of antibodies with higher affinity for the antigen) and
immunoglobulin heavy chain class switching. Memory cells are generated
• T-cell independent responses are induced by polysaccharide, lipid antigens and other small
chemicals. These responses generally do not show affinity maturation or class switching and
memory cells are generally not produced
• B-cell stimulation begins with the cross-linking of antigen receptors (IgD or IgM) by antigen
binding *. This induces:
• B-cells ingest process and display peptide antigens in association with MHC class II *
• CD4 positive T cells that recognise antigen displayed by B-cells are induced to express the
ligand for CD40 (CD40L) which interacts with CD40 on B-cells. The T-cells then secrete
cytokines (interferon gamma for TH1 cells and interleukin-4 for TH2 cells) - IFN-gamma
stimulates B-cells to secrete IgG (TH1 antibody) while IL-4 stimulates the production of IgE
(TH2 antibody) - CLASS SWITCHING. This does not occur in the absence of CD40 or CD40L *
• Affinity maturation occurs in the germinal centres of the lymphoid follicles and is caused by
somatic hyper-mutation of the immunoglobulin gene in dividing B-cells and the production of
antibodies with different affinities. Cells that bind strongly to antigen on follicular dendritic cells
are rescued, while the rest undergo apoptosis. As the infection subsides, there is less antigen
and therefore only B-cells producing higher affinity antibodies are selected*
Question 1: With respect to the structure of antibodies
True False
b. Each antibody molecule has two identical Fab regions
True False
c. Each antibody molecule has two Fc regions
True False
d. The hinge region is located between the Fab and the Fc regions
True False
Question 2: IgD
True False
b. Is glycosylated
True False
c. Activates complement
True False
d. Sensitizes mast cells
True False
Question 3: IgE
True False
b. Binds to macrophages and polymorphs
True False
c. Is increased in parasitic infections
True False
d. Makes up 10% of serum immunoglobulins
True False
Question 4: IgG
a. Is glycosylated
True False
b. Has a molecular weight of 150kDa
True False
c. Makes up 30% of total serum immunoglobulins
True False
d. Is not present in extra-vascular fluid
True False
Question 5: IgM
True False
b. Sensitizes mast cells
True False
c. Is not glycosylated
True False
d. Binds to macrophages and polymorphs
True False
True False
b. Affinity maturation is caused by somatic hypermutation of immunoglobulin genes
True False
c. IgE secretion is stimulated by interferon gamma
True False
d. IgG secretion is stimulated by interleukin-4
True False
Question 7: Antibodies
True False
b. May be membrane-bound
True False
c. Are present in breast milk
True False
d. Do not cross the placenta
True False
True False
b. Increased expression of cytokine receptors
True False
c. Migration out of lymphoid follicles
True False
d. Secretion of large quantities of IgG
True False
Question 9: The following antigens induce T-cell dependent B-cell antibody production
a. Peptide antigens
True False
b. Polysaccharide antigens
True False
c. Lipid antigens
True False
d. Nucleic acid antigens
True False
a. Are alpha-globulins
True False
b. Have receptors on macrophages
True False
c. Do not recognise lipid antigens
True False
d. Do not recognise nucleic acid antigens
True False
a. Opsonises bacteria
True False
b. Is important in the passive immunity of the neonate
True False
c. Activates antibody-dependent cell mediated cytotoxicity
True False
d. Serves as antigen receptor on B-cells
True False
True False
b. Each heavy chain has three variable domains
True False
c. Each variable domain on the heavy or light chain has three hyper-variable regions
True False
d. The Fab fragment consists of the entire light chain attached to the variable and first constant
domain of the heavy chain
True False
True False
b. Activates complement via the classical pathway
True False
c. Sensitizes mast cells
True False
d. Is responsible for atopic allergy
True False
True False
b. Binds to mast cells
True False
c. Is synthesised by plasma cells
True False
d. Is smaller than IgE
True False
True False
b. There are two different types of heavy chains
True False
c. Antibodies of identical specificity but containing different heavy chains are said to belong to
different isotypes or classes
True False
d. IgA has five sub-types
True False
ANTIGEN PROCESSING AND PRESENTATION
EXTRACELLULAR ANTIGENS
• Newly synthesised class II molecules have a peptide called the class II invariant chain peptide
(CLIP) tightly bound to the peptide binding cleft
• When exocytic vesicles containing newly synthesised class II molecules fuse with endosomal
vesicles containing degraded peptides, CLIP is removed and the peptide binding site is free to
bind peptides derived from degraded extracellular antigens
• Only class II molecules that display a peptide are expressed on the cell surface. Molecules
without peptides are unstable and degraded by proteolysis
CYTOSOLIC ANTIGENS
• Derived from microbes within the cytosol and other 'self' cytosolic proteins
• Peptides are transported from the proteasomes into the endoplasmic reticulum by the
transporter associated with antigen processing (TAP). The normal route of transport of
peptides is from the endoplasmic reticulum into the cytosol following protein synthesis.
• As the peptides enter the ER, they are bound by class I molecules (class II molecules cannot
bind peptides here because they contain CLIP)
• Only class I molecules containing peptide are displayed on the cell surface. Molecules without
peptide are degraded. Self and non-self peptides are displayed.
• The main TH2 cytokine is interleukin-4: stimulates the production of IgE. Interleukin-5 activates
eosinophils while other cytokines including IL-4 inhibit macrophage activity. TH2 cells therefore
stimulate phagocyte-independent, eosinophil mediated immunity - particularly important against
helminthic parasites
T-CELL BINDING TO ANTIGEN-PRESENTING CELLS
• The binding of T-cells to antigens is of low affinity and needs to be stabilised to enable cell
activation
• Stability is provided by cell adhesion molecules, of which integrins are the most important
group.
• The major T-cell integrin involved in binding to antigen presenting cells is the lymphocyte
function-associated antigen-1 (LFA-1). Its ligand is the intercellular cell adhesion molecule-1
(ICAM-1) which is expressed by antigen presenting cells
• LFA-1 on nagative T-cells has a low affinity for ICAM-1. Chemokines produced by the innate
immune system and antigen recognition by T-cells increases the affinity of LFA-1 for ICAM-1
• B-lymphocyte maturation occurs in the bone marrow while T-lymphocyte maturation occurs in
the thymus
• The proliferation of pro-B and pro-T cells is stimulated by interleukin-7 secreted by the bone
marrow or thymus
• There is a need to generate receptors that can recognise all the possible antigens that the cells
may encounter
• Diversity is generated by somatic recombination of genes that code for the variable regions of
the receptors
• All antigen receptor gene loci have contain several hundred variable region (V) genes and a
few constant region (C) genes - this applies to the immunoglobulin light and heavy chain and
the T-cell receptor alpha and beta chain
• Between the variable and constant genes are several stretches of nucleotides called joining (J)
and diversity (D) segments. All antigen receptor gene loci contain J segments but only the
immunoglobulin heavy chain and the T-cell receptor beta loci have D segments
• Diversity of antigen receptors is therefore generated by the use of different V, D & J gene
segments in different clones of lymphocytes (Combinatorial diversity). In addition, further
diversity is generated by nucleotide changes at the junctions of V, D & J genes (junctional
diversity)
• Positive selection occurs only during T-cell maturation. As T-cells only recognise antigens
displayed by MHC, cells that do not recognise MHC molecules in the thymus die by apoptosis.
These cells would otherwise be useless
• Negative selection occurs during both B and T cell maturation ?- cells expressing receptors
that bind strongly to antigens within the thymus (MHC associated) or in the bone marrow either
undergo apoptosis or further maturation is stopped. These cells would otherwise react strongly
to –self- antigens. In B-cells, recombination may be re-activated to generate a new light chain -
receptor editing
• Allelic exclusion occurs during both B-and T-cell maturation: once a receptor has been
synthesised, further recombination at un-recombined loci is shut-off, so that a receptor is
generated from one of the inherited parental alleles only
• Only recognises peptide antigens displayed by MHC molecules. Does not recognise lipid,
polysaccharide or nucleic acid antigens *
• Each receptor has an alpha and a beta chain each with a variable and a constant domain
homologous to those on immunoglobulins
B-LYMPHOCYTES *****
• Mature in the bone marrow. Develop into antibody producing
plasma cells. Only immune cells capable of antibody production *
1) Stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into
aclone of cells with identical BCRs;
T-LYMPHOCYTES *****
• Can only recognise peptide antigens that are bound to MHC molecules
on specialised antigen-presenting cells - MHC-restricted *
• CD8 positive T-cells are cytotoxic T-cells - capable of killing host cells
infected with intracellular organisms *
• The role of the CD8+ T cells is to monitor all the cells of the body,
ready to destroy any that express foreign antigen fragments in their
class I molecules.
CD4+ T cells
• All nucleated cells can present antigens derived from microbes in the
cytoplasm to cytotoxic T-cells *
Langerhans cells
• Lymph drains from the efferent lymphatics into the sub-capsular sinus
and then through the medullary sinuses into the efferent lymph vessels
• B-cells are concentrated in the cortex where they form follicles. Un-
stimulated B-cells form primary follicles while secondary follicles are
formed following antigenic stimulation. Secondary follicles have a
germinal centre which is the site of B-cell maturation and the
generation of B-cell memory
• Na-ve T-cells leave the circulation to enter the lymph nodes through
specialised post-capillary venules called high endothelial venules
SPLEEN ***
• The red pulp is the red cell area - the spleenic capillaries are very
porous and red cells leave the capillaries to enter the red pulp. They
then squeeze through the trabeculae which are lined by a vast number
of macrophages to re-enter the circulation at the venous end
• Old red cells and platelets are removed from the circulation in the
spleen
Immune cells & distribution *****
Cell type Number/litre in blood Life-span after Distribution
of adults leaving bone
marrow
Mast cells
• Made up of membrane bound proteins on antigen presenting cells that display peptide antigens
for recognition by T-cells *
• MHC genes are highly polymorphic - there are many different alleles present in different
individuals. No two individuals in an outbred population have identical MHC genes or
molecules (except identical twins) *
• There are two sets of highly polymorphic HLA genes called class I and class II genes
• The MHC also contains several non-polymorphic genes, some involved in antigen presentation
and others with unknown functions
• Class I molecules are expressed by all nucleated cells while class II molecules are expressed
by professional antigen-presenting cells only (dendritic cells, macrophages and B-
lymphocytes) *
• Each MHC molecule can only present one antigen at a time, but is capable of presenting many
different peptides. The binding of peptides to MHC molecules is a low affinity, low specificity
interaction. Bound peptides are displayed for several days to enable recognition by T-cells
• Antigenic peptides are acquired during the synthesis and assembly of MHC molecules in the
cytoplasm - class I molecules display peptides acquired from cytosolic proteins while class II
molecules acquire peptides from intracellular vesicles
• Each person inherits one set from each parent, therefore each cell can express 6 different
class I molecules *
• The alpha chain has three domains: the alpha1 and alpha2 domains are highly polymorphic
and surround a peptide binding cleft which is capable of binding peptides with 8-11 amino acids
• The alpha3 domain is invariant and contains the binding site for the T-cell receptor CD8
• CD8 positive T cells can therefore only respond to peptide antigens displayed by class I MHC
molecules
• Each person inherits one set from each parent, therefore each cell can express 6 different
class II molecules *
• The peptide binding site for class II molecules can bind peptides with 10-30 amino acids
• The beta2 domain on the beta chain of class II molecules is invariant and contains the binding
site for the T-cell receptor CD4
• CD4 positive cells can therefore only recognise peptide antigens displayed by MHC class II
molecules
Question 1: With respect to lymphocyte maturation and the generation of diversity
True False
b. T-cell maturation occurs in the thymus gland
True False
c. Proliferation of lymphocyte precursors is under the stimulation of TNF-alpha
True False
d. Positive selection occurs during B-cell maturation
True False
True False
b. T-lymphocytes mature in the thymus gland
True False
c. Na?ve lymphocytes do not express antigen receptors
True False
d. T-cells are MHC-restricted
True False
True False
b. TH1 cells stimulate the production of IgE antibodies
True False
c. TH2 cells are CD8 positive
True False
d. TH1 cells stimulate phagocyte-mediated killing of microbes
True False
True False
b. Cytokines secreted by TH2 cells activate macrophages
True False
c. Interleukin-12 stimulates the differentiation of helper T-cells into TH2 cells
True False
d. TH2 cells secrete interleukin-4
True False
Question 5: Lymphocytes
a. Are the only immune cells with specific receptors for antigens
True False
b. Make up 5% of the total leukocyte count
True False
c. Count is increased in viral infections
True False
d. Count is increased following corticosteroid therapy
True False
True False
b. Class I & II MHC molecules contain a peptide-binding domain at the amino-terminal end
True False
c. MHC antigens are inherited in an autosomal dominant fashion
True False
d. Class I MHC antigens are expressed by professional antigen-presenting cells only
True False
True False
b. Does not recognise lipid antigens
True False
c. Only recognises antigens displayed by MHC molecules
True False
d. Recognises the three dimensional conformation of antigens
True False
True False
b. Class II molecules are expressed by B-lymphocytes
True False
c. Class II molecules are not expressed by macrophages
True False
d. Class I but not class II MHC molecules have polymorphic genes
True False
a. Antigens within the cytosol are displayed by class I MHC molecules only
True False
b. Antigens within phagocytic vesicles are processed and presented by both MHC class I and
class II molecules
True False
c. Only foreign cytosolic proteins are displayed on MHC molecules
True False
d. The peptide binding cleft of newly synthesised MHC class II molecules contains the class II
invariant chain peptide
True False
a. MHC molecules acquire antigenic peptides during their biosynthesis within the cell
True False
b. Class I MHC molecules acquire antigenic peptides from proteins in intracellular vesicles
True False
c. Class II MHC molecules acquire antigenic peptides from cytosolic proteins
True False
d. MHC molecules cannot discriminate between foreign and self antigens
True False
True False
b. B-cells are located in the red pulp
True False
c. The capillaries are lined by endothelial cells with tight junctions
True False
d. The trabeculae of the red pulp contain macrophages
True False
True False
b. Helper T-cells help B-lymphocytes to produce antibodies
True False
c. Helper T-cells help phagocytes to destroy ingested microbes
True False
d. CD8 positive T-lymphocytes are helper T-cells
True False
a. CD4 positive T-cells can only respond to antigens presented by class II MHC molecules
True False
b. There are three polymorphic MHC class I genes in humans
True False
c. Each human cell expresses three different MHC class I molecules
True False
d. Humans have four polymorphic MHC class II genes
True False
True False
b. TH2 cells are CD8 positive
True False
c. TH1 cells produce interferon-gamma
True False
d. TH2 cells produce mainly interleukin-12
True False
a. Dendritic cells
True False
b. Macrophages
True False
c. Langerhans cells
True False
d. B-cells
True False
GRAFT REJECTION *****
HYPERACUTE REJECTION
• Antibody mediated response caused by pre-existing antibodies that may have developed as a
result of previous blood transfusion - therefore more likely to occur in those with previous
transfusion
• Corneal and cartilage transplants are not rejected as these are avascular structures and
therefore do not sensitize the recipient
ACUTE REJECTION
• Early acute rejection is a cell mediated hypersensitivity reaction (T-cell) although antibody
mediated hypersensitivity also contributes
• Occurs over several months / years and manifests as a gradual loss of graft function
• T-cell mediated response with the production of cytokines which induce fibrosis and
proliferation of vascular smooth muscle
• May follow bone marrow transplant or occur as a result of T-cells present in transplanted
organs
The reaction is greater the greater the HLA difference between the host and the donor.
May be fatal
IMMEDIATE (TYPE I) HYPERSENSITIVITY *****
• Rapid IgE and mast cell dependent vascular and smooth muscle reaction that is usually
followed by an inflammatory reaction in an individual who has been previously exposed to an
antigen (sensitized) *
• Antigen binds to IgE on mast cells, cross-linking receptors and inducing mast cell
degranulation *
• Released mast cell granules contain histamine, heparin, neutral proteases and cytokines
typical of TH2 responses - IL-3 and IL-4 *
• Cyclo-oxygenase and lipoxygenase are also activated with the production of vasodilator
prostaglandins, leukotrienes and thromboxanes *
• The result is increased capillary permeability, smooth muscle contraction and this manifests as
wheezing, oedema, hypotension - this is the acute phase and occurs within minutes *
• The latent phase peaks after 3-5 hours and is caused by cytokine mediated inflammatory
infiltration by neutrophils and eosinophils - this is responsible for tissue damage that occurs
after repeated episodes of immediate hypersensitivity *
• Typical disease processes include asthma, hay fever, drug and insect bite induced
anaphylaxis, penicillin allergy, food allergy, atopic dermatitis *
• Disorders include *
6) Pernicious anaemia
• These complexes activate macrophages, activate complement and cause the extracellular
release of neutrophil granules and tissue damage *
3) Post-streptococcal glomerulonephritis
4) Jarisch-Herxheimer reaction
• Occurs in allergic reactions to bacteria, fungi and viruses, contact dermatitis and in the
rejection of transplanted tissues *
• Typically occurs in the Mantoux reaction to tuberculin injected in the skin of a sensitized
individual - characterised by erythema and induration *
• Reaction occurs after several hours and peaks 24-48h after contact *
• The early phase is characterised by a perivascular cuffing with mononuclear cells, and then
polymorphs which later leave. The late phase is characterised by a lymphocyte and monocyte-
macrophage infiltration *
• Antigen interacts with primed T-cells with tissue damage resulting from inappropriate cell
mediated immune reactions
• The chronic inflammatory response leads to the formation of granulomas, which may be
caseating in the case of TB *
Occurs in Crohn's disease, psoriasis, celiac disease, TB, leprosy, contact dermatitis,
tissue damage following measles and herpes infection; schistosomiasis *
PASSIVE IMMUNOTHERAPY *****
• The use of immunoglobulins to treat or prevent disease. Antibodies may be from human or
animal sources or may be genetically engineered
• Associated with serum sickness especially when antibodies are from an animal source
3) Hepatitis B
• Maternal IgG is actively transported by the placenta into the fetus. IgA is not taken up by the
placenta *
• Secreted IgA in breast milk is not absorbed but confers mucosal immunity in the GI tract *
VACCINATION *****
Types of Vaccines
• Killed organisms
• Live-attenuated organisms replicate in the host. Provide a larger –does- and have the
advantage of inducing immunity at the natural site of infection
• Sub-unit vaccines - make use of the most antigenic subunit of the organism. These can be
produced by genetic engineering
BACTERIAL
Live Attenuated
• BCG - tuberculosis
Inactivated
• Cholera vaccine
• Pertussis vaccine
• Typhoid vaccine
Sub-unit
• H. influenzae
• N. meningitides
• S. pneumoniae
Toxoid
• Tetanus
• Diphtheria
VIRUSES
Live Attenuated
• Polio (Sabin)
• Adenovirus
• Yellow fever
Inactivated
• Polio (Salk)
• Influenza
• Rabies
• Hepatitis A
Sub-unit
• Hepatitis B
• Influenza
Question 1: Hyperacute transplant rejection
a. Is mediated by T-lymphocytes
True False
b. Is a TH1 response
True False
c. Is more likely to occur in patients who have never had a previous blood transfusion
True False
d. Is the commonest type of transplant rejection
True False
a. Tetanus vaccine
True False
b. Diphtheria vaccine
True False
c. Mumps vaccine
True False
d. Hepatitis A vaccine
True False
True False
b. Smooth muscle relaxation
True False
c. Hypertension
True False
d. Oedema
True False
True False
b. Salk polio vaccine
True False
c. Hepatitis B vaccine
True False
d. Rubella vaccine
True False
True False
b. Only occurs following bone marrow transplant
True False
c. Occurs when transplanted leukocytes are rejected by the host
True False
d. Is of greater severity if the donor and the recipient have a greater HLA difference
True False
a. Rash
True False
b. Diarrhoea
True False
c. Weight loss
True False
d. An immuno-competent transplant recipient
True False
Question 7: The following are typically released following mast cell degranulation
a. Histamine
True False
b. Vasoconstrictor prostaglandins
True False
c. Neutral proteases
True False
d. Leukotrienes
True False
True False
b. Extrinsic allergic alveolitis
True False
c. Goodpasture?s syndrome
True False
d. Drug-induced haemolytic anaemia
True False
True False
b. The trans-placental transfer of IgA
True False
c. The uptake of IgA from the gut
True False
d. The uptake of IgG from the gut
True False
True False
b. Fever
True False
c. Haemolytic anaemia
True False
d. Splenomegaly
True False
True False
b. Is IgD dependent
True False
c. Occurs when an individual encounters an antigen for the first time
True False
d. Has an early and a late phase
True False
Question 12: The following disorders are currently treated by passive immunotherapy
a. Tetanus
True False
b. Diphtheria
True False
c. Botulism
True False
d. Hepatitis B
True False
True False
b. Scleroderma
True False
c. Auto-immune thrombocytopaenia
True False
d. Graves disease
True False
True False
b. Occurs in drug-induced haemolytic anaemia
True False
c. Is characterised by the Arthus reaction
True False
d. Occurs in myasthenia gravis
True False
a. Rubella vaccine
True False
b. Yellow fever vaccine
True False
c. Polio vaccine
True False
d. Adenovirus vaccine
True False
40 random questions for EMQ Mock Exam
Instructions: For each of the events below, choose the single most appropriate time period from the
above list (list indicates time after fertilisation). Each option may be used once, more than once or not at
all
A Promethazine B Ranitidine
C Sodium chromoglycate D Methyldopa
E Chlorpheniramine F Cimetidine
G Cyproterone acetate H Chlorpromazine
I Omeprazole J Tubocurarine
Instructions: Histamine antagonists are widely used therapeutically. For each of the questions below,
choose the singlemost appropriate drug from the above list. Each option may be used once, more than
once or not at all
A Rubella B Influenza A
C Human papilloma virus type 16 D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Hepatitis C J Hepatitis E
Instructions: Infections in pregnancy may be associated with fetal / neonatal adverse effects. For each
of the scenarios below, choose the single most appropriate micro-organism from the above list. Each
option may be used once, more than once or not at all.
A Rubella B Influenza A
C Cytomegalovirus D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal adverse effects. For each of the
questions below, choose the single most appropriate micro-organism from the above list. Each option
may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
Instructions: For each of the organs / structures listed below, select the single most appropriate nerve
supply from the above list. Each option may be used once, more than once or not at all
Instructions: For each of the events below, choose the single most appropriate time period from the
above list (list indicates time after fertilisation). Each option may be used once, more than once or not at
all
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
A Cimetidine B Ranitidine
C Sodium chromoglycate D Tubocurarine
E Chlorpheniramine F Atropine
G Cyproterone acetate H Chlorpromazine
I Lanzoprazole J Omeprazole
Instructions: Histamine antagonists are widely used therapeutically. For each of the questions below,
choose the singlemost appropriate drug from the above list. Each option may be used once, more than
once or not at all
A Rubella B Influenza A
C Human papilloma virus type 16 D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal adverse effects. For each of the
questions below, choose the single most appropriate micro-organism from the above list. Each option
may be used once, more than once or not at all.
Instructions: For each of the structures / organs below, choose the single most appropriate type of
epithelium from the above list. Each option may be used once, more than once or not at all
Instructions: Nucleic acid replication is vital for cell division. For each of the questions below, choose
the single most appropriate option from the above list. Each option may be used once, more than once
or not at all.
Instructions: For each of the hormones listed below, select the single most appropriate site of
synthesis from the above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, select the single most appropriate hormone from the
above list. Each option may be used once, more than once or not at all.
A Interferons B IgA
C IgG D Immunoglobulins
E Cytokines F IgE
G Prostaglandins H Interleukins
I IgM J IgD
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the structures / organs below, choose the single most appropriate type of
epithelium from the above list. Each option may be used once, more than once or not at all
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
Question 35 Coagulase positive gram positive bacteria
Instructions: A 30 year old woman suffered post-partum haemorrhage of 1,500ml following forceps
delivery for delay in the second stage. For each of the questions below, select the single most
appropriate option from the above list. Each option may be used once, more than once or not at all
Instructions: For each of the scenarios below, select the single most appropriate hormone from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
A Interferons B Endotoxins
C Exotoxins D Immunoglobulins
E Cytokines F Histamine
G Prostaglandins H Interleukins
I Tumour necrosis factor J Lipopolysaccharide
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
A Rubella B Influenza A
C Human papilloma virus type 16 D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Hepatitis C J Hepatitis E
Instructions: Infections in pregnancy may be associated with fetal / neonatal adverse effects. For each
of the scenarios below, choose the single most appropriate micro-organism from the above list. Each
option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
A Rubella B Influenza A
C Cytomegalovirus D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal adverse effects. For each of the
questions below, choose the single most appropriate micro-organism from the above list. Each option
may be used once, more than once or not at all.
A Interferons B IgA
C IgG D Immunoglobulins
E Cytokines F IgE
G Prostaglandins H Interleukins
I IgM J IgD
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
A Interferons B IgA
C IgG D Immunoglobulins
E Cytokines F IgE
G Prostaglandins H Interleukins
I Exotoxins J IgD
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
A Rubella B Influenza A
C Cytomegalovirus D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal adverse effects. For each of the
questions below, choose the single most appropriate micro-organism from the above list. Each option
may be used once, more than once or not at all.
A Interferons B IgA
C IgG D Immunoglobulins
E Cytokines F IgE
G Prostaglandins H Interleukins
I IgM J IgD
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
A Rubella B Influenza A
C Human papilloma virus type 16 D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal adverse effects. For each of the
questions below, choose the single most appropriate micro-organism from the above list. Each option
may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate antibiotic from the
above list. Each option may be used once, more than once or not at all.
C Immune complex mediated (Type III) D Delayed cell mediated (type IV)
hypersensitivity hypersensitivity
E Graft versus host disease F Acute graft rejection
G Hyperacute graft rejection H Chronic graft rejection
I Allergic Reaction J Jerisch-Herxheimer reaction
Instructions: For each of the scenarios below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
A Rubella B Influenza A
C Human papilloma virus type 16 D Parvovirus B19
E Coxsackie B virus F Hepatitis A
G Hepatitis B H HIV
I Toxoplasmosis J Varicella zoster
Instructions: Infections in pregnancy may be associated with fetal / neonatal adverse effects. For each
of the scenarios below, choose the single most appropriate micro-organism from the above list. Each
option may be used once, more than once or not at all.
A Interferons B IgA
C IgG D Immunoglobulins
E Cytokines F IgE
G Prostaglandins H Interleukins
I Exotoxins J IgD
Instructions: For each of the statements below, choose the single most appropriate option from the
above list. Each option may be used once, more than once or not at all.
Instructions: For each of the scenarios below, choose the single most appropriate micro-organism
from the above list. Each option may be used once, more than once or not at all.
• Protein synthesis
BACTERIAL RESISTANCE
CAUSED BY:
• Single gene mutations - random events, with the mutant that results in resistance being
selected in the presence of the antibiotic
• Transposons - 'jumping genes' - resistance genes that are capable of intergration into the
chromosome or plasmids
• Effective against all gram positive bacteria and gram negative cocci
• Cycloserine - inhibits reactions incorporating alanine into cell wall precursor within the
cytoplasm
GLYCOPEPTIDES ****
• Vancomycin and teicoplanin
• Inhibit bacterial cell wall synthesis by binding to d-alanyl-d-alanine at the end of a pentapeptide
chain, preventing the incorporation of new subunits
• Large molecules which cannot penetrate gram negative cell wall. Only active against gram
positive bacteria
• Not absorbed from the GI tract. Oral administration used to treat Clostridium difficile diarrhoea
• Inhibit bacterial protein synthesis *- interfere with the binding of formylmethionyl-transfer RNA
to the ribosomes, preventing the formation of the initiation complex
• Not absorbed from the GI tract.* Do not cross the blood-brain barrier
TETRACYCLINES *****
• Inhibit bacterial protein synthesis by preventing aminoacyl tRNA from entering the acceptor
site on ribosomes *
• Absorbed from the gut. Doxycycline and minocycline are better absorbed than the others *
CHLORAMPHENICOL
• Active against a wide range of bacteria. Main indication is the treatment of Salmonella typhi
MACROGLIDES *****
• Well absorbed from the gut; penetrate tissues well and are active against intracellular
organisms *
• Erythromycin is concentrated in the liver and excreted via bile
CLINDAMYCIN *****
• Similar antibiotic spectrum to erythromycin, excreted by the liver, active in faeces for up to 5
days after a dose
• More active against anaerobes than erythromycin. Clostridium difficile is resistant and may be
selected, causing pseudomembranous colitis
ANTI-FUNGAL AGENTS
ANTI-VIRAL AGENTS
• Zidovudine- HIV
• Clue cells - vaginal epithelial cells coated with gram-variable bacteria on wet vaginal smear *
• Positive amine test - pungent fishy odour on adding the vaginal discharge to sodium hydroxide
• Associated with an alteration in vaginal flora with decreased lactobacilli and increased
anaerobes and Gaednerella vaginalis
Gardnerella vaginalis
• Gram variable, can be isolated from the vaginal flora in 20% of asymptomatic women
and present in the urethra of male partners of women with bacterial vaginosis
TRICHOMONAS VAGINALIS
• Flagellated protozoan, anaerobic, readily cultured on Diamond’s medium
• Sexually transmitted
• The organism is difficult to detect in males but can be isolated from prostatic fluid
• Causes candidiasis
• Yeast-like fungus, grows by budding and may produce long non-branching filaments
called pseudohyphae. Candida is a polymorphic yeast, i.e., yeast cells, hyphae and
pseudohyphae are produced *
• Non-motile gram negative or gram variable although gram stain is not useful in diagnosis *
• Does not infect squamous cells - the vaginal epithelium and ectocervix are not infected.
Endocervical glands are susceptible *
• Produce infectious particles called Elementary Bodies which enter cells by endocytosis
• Differentiate into Reticulate Bodies within cells. These multiply by binary fission and then
produce other elementary bodies which are released from the cell
Various serovars:
• A - C: Trachoma (blindness)
DIAGNOSIS
• Immuno-fluorescence
• Serology - unreliable
TREATMENT
• Erythromycin
LYMPHOGRANULOMA VENEREUM
• Sensitive to tetracycline
• Fragile organism - very sensitive to drying and low temperature- swabs should be collected
in Stuart's transport medium, maintained at room temperature * and cultured on selective VCT
medium (vancomycin, collistin, trimethoprim). Grows on blood or chocolate agar
• Neisseria meningitides is carried in the nasopharynx of 5-30%of adults and is one of the
three primary pathogens causing bacterial meningitis
INFECTION
• Males: 20% chance; Females: 50% chance of being infected after one episode of unprotected
intercourse with infected partner
TREATMENT *
• Ciprofloxacin
• Spectinomycin
• Azythromycin
• Contrat tracing required
REITER’S SYNDROME *
• Commoner in males
• Facultative anaerobes
• Produce endotoxins (gram positive bacteria produce exotoxins) but E. coli also produces an
enterotoxin (exotoxin) which causes diarrhoea by stimulating epithelial adenylate cyclase
• Klebsiella is resistant to ampicillin. Other community acquired colifirms are generally sensitive
to ampicillin
• Hospital acquired coloforms are generally resistant to ampicillin but sensitive to gentamicin and
third generation cephalosporins
• Strict aerobes *
• The bacterium is ubiquitous in soil and water, and on surfaces in contact with soil or
water. They occur regularly on the surfaces of plants and occassionally on the surfaces of
animals.
• The bacterium almost never infects uncompromised tissues, yet there is hardly any tissue that
it cannot infect if the tissue defenses are compromised in some manner
• Causes chronic UTIs, wound infections, chronic osteomyelitis and opportunistic infections
VIBRIOS
• Non-motile
• Infected individual is infectious for up to three weeks after the onset of symptoms
• Infection may occur at any age but most common and more severe in infants below the age of
1 year *
• In children, lymphocytosis is often profound (>70% of the total WBC count). The WBC count
often rises to 20-40,000 cells/mm2; and may rise to 100,000 cells/mm2 *
• Cultures are typically negative soon after the onset of the paroxysmal stage
• Infection is preventable by vaccination using killed organism. Does not produce a toxin
HAEMOPHILUS INFLUENZAE
LEGIONELLA PNEUMOPHILIA
• Is spread by droplet infection via contaminated air conditioning systems and shower mixers
• Sensitive to erythromycin
BACTERIODES *****
• Non-spore forming *
ENDOTOXINS
• Present in the outer layer of the cell wall of gram negative bacteria,
released on disintergration
• RNA virus
• Spread by the feco-oral route although sexual transmission may
occur
HEPATITIS B *****
• DNA virus
Serology
HEPATITIS C
• RNA virus
• DefectiveRNA virus
HEPATITIS E
• RNA virus
• DNA virus
• However, the prevalence of oro-genital sexual practices means that this distinction is
less evident
• Virus remains dormant in dorsal root ganglia, causing recurrent infection. Average
number of recurrences per year = 4. Less severe symptoms *
• Virus can be shed from the genital tract and transmit infection in the absence of
symptoms or a prodrome
• Vertical transmission causes neonatal disseminated herpes which has high mortality /
morbidity. Does not cause congenital anomalies.
Diagnosis
• Clinical
• Viral culture - negative culture does not exclude infection. The longer the duration of
symptoms, the less likely is a swab to be positive
• Electron microscopy
• ELISA / PCR
Treatment
• Symptomatic
• Acyclovir
VARICELLA ZOSTER
• Contagious 48h before onset of rash until all vesicles have crusted over
• Severs infection may cause pneumonitis, encephalitis, myocarditis and adrenal
insufficiency
• Virus remains dormant in the dorsal root ganglia, causing recurrent infection
(shingles, Herpes zoster). Shingles is contagious
CYTOMEGALOVIRUS *****
• DNA virus, member of the Herpes family of viruses *
• Primary infection usually asymptomatic but may produce an illness that is clinically
indistinguishable from Epstein-Barr mononucleosis (glandular fever)
• Can be cultured from urine of infected individuals. Excretion may persist for years *
• Recurrences are common and fetal infection may occur during recurrence. Maternal
immunity (presence of IgG does not prevent recurrence or fetal infection)
Infection
Details
Typhoid
Cytomegalovirus
Leptospirosis *
Infected rodents excrete virus in urine
Lassa fever
Details
Infection in childhood
Herpes simplex *
Mumps
CMV
Epstein-Barr virus *
Rabies
Pasteurella multocida
Type of milk
Human milk
Mumps virus
Human milk
CMV *
Human milk
HIV
Brucella
Cow milk
Mycobacterium bovis
Cow milk
Salmonella
Cow milk
Listeriosis *
Cow milk
Streptococcal infection
HUMAN PAPILLOMA VIRUS *****
• DNA virus
• Types 16 and 18 are associated with CIN and cervical cancer - high
risk HPV. Also associated with oral and vulval carcinoma and VIN
• RNA virus
Vertical Transmission
• 15-20% vertical transmission rate without treatment
• 2/3rd transmission occurs around the time of delivery
• Disinfection - removes or kills most, but not all viable organisms. Uses chemical
or physical processes
• Moist heat (autoclaving) - most effective method of sterilisation. Usual cycle is 121C
for 15 minutes - sufficient to kill spores of Clostridium botulinum. Heat-sensitive
instruments such as endoscopes -use low temperature steam + formaldehyde
• Boiling - disinfects but does not sterilise -some spores are not killed
• Gamma irradiation - useful for sterilising large batches of small items such as
needles
• Iodine / iodophors -kills some spores, inactivated by blood and other organic
matter; iodine stains skin and can cause local sensitivity
• Alcohols - effective only in the presence of water (70% alcohol). Isopropyl alcohol
better for skin. Inactive against spores and fungi, inflammable
• Hypochlorite and chlorine -active against fungi, viruses (including HepB and HIV),
and spores as well as bacteria. Easily inactivated by organic material- not used for
skin disinfection
INFLUENZA
Three types
• Staph aureus strains known as MRSA have now also become resistant to methicillin
and flucloxacillin. Infections most common in hospitals in-patients and are rarely seen
in the community.
• Colonisation with Staph. aureus is very common. Some individuals are colonised
with MRSA (skin or nose / pharynx usually). Wounds (including surgical), indwelling
catheters or burns and immuno-deficiency increase the risk of MRSA infection.
• Spread by direct physical contact although organisms in the nose or lungs can be
spread by droplet infection
• Rarely causes infection in healthy people such as health care staff and their families.
However, MRSA may be introduced into unaffected areas by colonised staff
• Between 1 and 5 per cent of people being admitted to acute hospitals are probably
currently colonised with MRSA, and at least 50 per cent of these are not known about
prior to admission screening
• The sensitivity of detection of MRSA carriage depends on many the methods used
and the number and sites sampled.
• The perineum is the main carriage site on normal skin. Nose, lesions or wounds,
manipulated sites, intravenous and stoma sites, tracheostomies, perineum/groin, urine
from catheterised patients and sputum if available are usually tested
• Other swabs may be taken from the umbilicus in infants, faeces and vagina if
indicated. Other possible sites of carriage which may be relevant to certain outbreaks
include the axilla, vagina and skin of the buttock area in the elderly.
• The sensitivity of various sampling sites for detecting carriage is: nose alone 78.5%;
nose and throat 85.6%; nose and perineum 93.4%; nose, throat and perineum 98.3%.
Positive groin (15.6%) and axillary samples (10.1%) were less frequent than perineal
(38.1%) and throat (30.8%).
• Perineal carriage, the presence of large numbers of colonies from hair and fingers or
positive contact are all suggestive of heavy dispersal from carriers. The organisms are
commonly present in the air near the disperser and on the floor around the bed.
CONTROLLING MRSA
• Scrupulous hand washing by hospital staff between patients. Antiseptic detergents are
commonly used but a 70% alcohol handrub is more effective
• Colonised or infected patients should be informed of the finding and its implications
and identified for infection control purposes.
• This can be done by tagging their medical records, in a manner which preserve
confidentiality, so that they are recognised immediately on admission to hospital
• Infection control measures such as hand washing, the use of gloves, protective
clothing and damp dusting are of even greater importance if there are no isolation
cubicles, few wash hand basins and an open -Nightingale- ward design without
separate bays. However, the establishment of an isolation ward even on a temporary
basis is necessary during an outbreak
• The individual rooms used for isolation should preferably have an extraction system
removing air to the outside. This, and keeping the door closed, reduces spread
between cubicles
• Restricted access to colonised / infected patients - essential staff only
• Cleaning of the room with disinfectant as MRSA can survive on inanimate objects or
surfaces such as linen, sinks, floors and even mops used for cleaning. The organism
may survive in a domestic environment for anything from 3-4 days to several months.
Skin scales which in floor coverings may favour survival for 6 months or more.
• Antibiotic therapy should be reviewed as antibiotics have been identified as risk factors
for acquiring MRSA, although some recent data suggest that this might have been over-
estimated
• However, cultures from hospital environment are generally negative even during
MRSA outbreaks.
• Data on the persistence of MRSA colonisation vary, some showing that the majority
of patients remained colonised for 2-3 years while other studies showed that the
majority of patients became clear within a year provided they did not have
predisposing lesions such as open wounds or prostheses. Open skin lesions appear to
be the main risk factor for prolonged MRSA colonisation
• Hospitals may keep a list of known affected patients with the admissions or accident
and emergency department or have them identified on the hospital computer system,
so they are admitted directly to an isolation room.
• Patients may also be given cards indicating that they have been infected or colonised
with MRSA in the past. This has the benefit of informing staff if the patient is
admitted to a different hospital or health care centre for treatment.
TREATMENT
Colonisation
• Intranasal or topical mupirocin ointment (three times a day for 5 days) is effective in
the control of MRSA
• Animal data indicates that mupirocin is not terratogenic but human data are not
available
• Upon discharge, no additional precautions are needed for colonised patients so long
as their contacts are healthy
Infection
• Most MRSA strains remain sensitive to vancomycin and teicoplanin which are the
main agents used to treat infections
1. Acid fast- i.e. they do not destain with acid and alcohol once stained with
arylmethane dyes
2. Aerobic
4. Intracellular pathogens- the wall helps the organism to survive within the
macrophage by resisting oxidative damage *
Mycobacterium tuberculosis
• Slender, straight or slightly curved bacillus, non-motile, non-encapsulated and does not form
spores *
• Aerobic
Tuberculosis
• TB is a chronic disease and an infected person can spread the infective organism, M.
tuberculosis, to several contacts before being diagnosed
• Symptoms include severe weight loss, night sweats, chronic cough, haemoptis
• A person may be infected without developing disease or remain healthy and free of disease for
decades. The infecting organisms remain viable. Disease may be activated by malignancy,
immune suppression, old age or chronic ill-health
1) Clinical presentation
2) Radiology -CXR
Treatment
Tuberculin test
• Mantoux and Heaf tests are different types of tuberculin skin tests. The Heaf gun is used to
make multiple punctures at the skin site and is more convenient when large populations are to
be screened. However, there is a risk of transmitting blood-borne infections
• The results of both tests are best read on day 3 although the Mantoux test may become
positive on day 2
• Administered intra-dermally *
• Following intra-dermal vaccination a small indurated papule appears within one to three
weeks *
• Enlargement of the regional lymph nodes may develop after vaccination. Spontaneous
regression usually occurs within a few months *
• Disseminated BCG infection has been reported rarely after BCG vaccination, principally in
immunocompromised individuals
SPIROCHAETES *****
• Include Treponema (T. pallidum - syphilis, T. pertenue - Yaws, T. carateum - Pinta), Leptospira
(L. icterohaemorrhagica – Weil’s disease) and Borrelia (B. recurrentis - relapsing fever, B.
vincenti – Vincent’s infection) *
SYPHILIS
• Sexually transmitted infection caused by Treponema pallidum
• QUATERNARY
GUMMA
• Typically involves the skin and sub-cutaneous tissue, mucous membranes of the
upper respiratory tract, sub-periosteal sites of long bones and joint
DIAGNOSIS
• Primary: VDRL (+ve or -ve), FTA-Abs (+ve). FTA-Abs usually becomes positive
before VDRL
• The VDRL test becomes negative with treatment and can be used to monitor
treatment. The FTA-Abs test can remain positive for several years after adequate
treatment *
• SLE, and other auto-immune disorders, acquired haemolytic anaemia, leprosy and
drug addiction cause chronic biological false positives
TREATMENT
LEPTOSPIROSIS
Organisms
• Survive for long periods in stagnant water / wet soil and infection
occurs through abraded or intact skin, conjunctiva or mucous
membranes *
• Spread through blood to kidneys causing leptospiuria which
perpetuates the cycle of infection *
Diagnosis
Treatment
• Benzyl penicillin
• Gram positive
• Capsulated, aerobic
Alpha-Haemolytic
• Differentiated by Optochin disc test (S. pneumoniae shows zone of inhibition) and bile solubility
test (S. pneumoniae is soluble)
Beta-Haemolytic
• Complete lysis of red cells
• Lancefield group A: S. pyogenes- causes sore throat, skin and wound infections (erysipelas,
impetigo), rheumatic fever and acute glomerulonephritis. Strains causing scarlet fever produce
an exotoxin
• Lancefield group B: S. algalactiae - isolated from vagina, perineum and rectum; causes
neonatal septicaemia and meningitis
• Lancefield group D: S. fecalis - usually non-haemolytic. Isolated from gut, causes UTIs and
bacterial endocarditis
Gamma Haemolytic
• Non haemolytic
• S. fecalis
STAPHYLOCOCCI ****
• Gram positive
• Grow on blood agar
• S. aureus: coagulase positive *- produce clot when mixed with serum. Also catalase positive
and produces exotoxin (toxic shock syndrome, toxic epidermal necrolysis). Non-motile *
• Plasmid mediated antibiotic resistance - can spread between different strains by transducing
phages. Produces beta-lactamase (penicillinase)
• S. aureus diseases include wound, bone and joint infections, breast abscess, skin and food-
borne infections, toxic shock syndrome. Isolated from the nose in 10-30% of healthy individuals
• Most often associated with the use of super-absorbent tampons and occasionally with the
use of contraceptive sponges. *
• The infection can also affect men, children and postmenopausal women.
• Signs and symptoms develop suddenly
Fatal ~ 5%.
• TSS has been linked to many bacterial infections, including pneumonia, osteomyelitis,
sinusitis, and skin and gynecologic infections
• Endotoxin toxic shock syndrome toxin-1 (TSST-1) is the major toxin produced by strains
of S aureus that are responsible for causing TSS.
• Streptococcus pyogenes exotoxin A (SPEA) and S pyogenes exotoxin B (SPEB) are the
major toxins produced by group A beta-hemolytic streptococci.
• The toxins activate production of cytokines, such as tumor necrosis factor, interleukin-1, M
protein, and gamma-interferon and induction of nitric oxide production which contributes to
hypotension. *
BACILLUS SPECIES
• Produces an exotoxin
• Sensitive to penicillin
CORYNEBACTERIUM DIPHTHERIAE
• Sensitive to penicillin; treatment with anti-toxin should be started once infection is suspected
• Anaerobic *
• Form part of the normal flora in the mouth, vagina and rectum.*
• Sensitive to penicillin *
CLOSTRIDIA
• Produce EXOTOXINS
• Infection common in gangrenous / ischaemic tissue and in association with foreign bodies
• CLOSTRIDIUM PERFRINGENS - Causes gas gangrene (causing crepitus) and septic abortion
(rare)
• Produces exotoxin causing septic shock, jaundice, haemolysis and acute renal failure
• Produces EXOTOXIN which is non-immunogenic therefore infection does not confer immunity.
Neurotoxin, inhibits release of inhibitory neurotransmitters in the CNS causing tetany / muscle
spasms
• There is no local inflammation associated with tissue infection
• Infection prevented by vaccination with tetanus toxoid in infancy followed by a booster dose
every 5-10 years
• Passive immunisation with human tetanus immune globulin + active immunisation required in
at-risk individuals following injury
• Antibiotic treatment is an ancillary measure and should include penicillin +/- flucloxacillin.
Removal of devitalised tissue, good tissue perfusion and oxygenation are essential *
• Beta-haemolytic
• Present in undercooked meats, soft cheeses, pate, coleslaw, contaminated milk. Can be
contracted from animal manure, silage and abortus material *
• Disease more common in third trimester of pregnancy. Infection in first trimester associated
with miscarriage. Third trimester infection associated with fetal death, meconium stained liquor,
chorio-amnionitis *
• Crosses placenta *
• Causes early (vertically acquired) and late (horizontally acquired) onset neonatal disease *
TRIMETHOPRIM *****
QUINOLONES *****
• Streptomycin
Rifampicin
METRONIDAZOLE *****
• A nitroimidazole
NITROFURANTOIN
• Absorbed from the gut and excreted in the uring in high enough
concentrations to inhibit bacteria
• Completes part of its life cycle in animals (mainly cats but also sheep, cattle and pigs)
• Contracted by contact with cat litter, infected soil or eating undercooked beef, lamb or pork.
Prevented by wearing gloves during gardening, thorough food hygiene and avoiding contact
with cat litter
• Oocysts or tissue cysts invades the intestinal epithelium , develop into trophozoites which
spread via the lymphatic system
• Infection is usually mild or asymptomatic with lymphadenopathy (posterior cervical) being the
main presentation. Causes severe disease with encephalitis and chorioretinitis in the
immunocompromised
• Risk of fetal infection increases with increasing gestation age (17% first, 25% second and 65%
third trimester)
• Detection of IgM or a 4 fold rise in IgG titres in samples 3 weeks apart is indicative of acute
infection
• Mode of transmission includes direct contact, food and milk products, saliva, faeces, urine,
blood or tissue
Bacterial zoonoses
3) Brucellosis - Brucella abortus from cattle and other species from sheep and
pigs. Infection acquired through contact with infected vaginal secretions or
products of conception (vets / farm workers)
8) Plague - Yersinia pestis, gram negative bacillus. Rats are animal reservoir
and the infection is passed to humans through the rat flea
10) Lyme disease - Borrelia burgdorferi, animal reservoir is the deer, passed to
humans by the hard ixodes tick
Rickettsial zoonoses
Chlamydial zoonoses
Viral zoonoses
• Rabies
• Lassa fever
Protozoal zoonoses
• Toxoplasmosis
• Leishmaniasis
• Yellow fever, dengue fever, haemorrhagic fever (viral) - housefly, sand fly, mosquitoe, ticks &
mites *
• Q-fever, Epidemic typhus (rickettsial) - lice, fleas, housefly, ticks & mites *
• Relapsing fever, Lyme disease (spirochaetes) - lice, fleas, housefly, ticks & mites
• Sleeping sickness, Chagas disease (trypanosomes -protozoan) - sand flies, mosquitoe, ticks *
Schistosomiasis
• Adult schistosomes live in the pelvic, mesenteric and portal venous systems of
humans
• Disease caused by deposition of ova in the liver, walls of the large bowel, bladder and
ureter *
• Fibrosis and granulomas develop around the ova causing polyps, strictures and pre-
malignant change *
• Ova penetrate the bladder / rectal wall to be excreted in the urine or faeces. Hatch in
water and larvae infect a specific species of snails. Cercariae emerge from the snail and
penetrate the skin of humans
• Serology - becomes positive before ova become apparent - positive result may persist
for a long time after treatment
a. There is a 2% risk of causing congenital varicella syndrome if infection occurs after 20 weeks
gestation
True False
b. Infection is preventable by passive immunisation
True False
c. Passive immunisation results in life-long immunity to infection
True False
d. Neonatal infection is unlikely if the baby is delivered within 4 days of maternal disease
True False
a. Is an RNA virus
True False
b. Type II herpes simplex virus typically causes oro-labial infection
True False
c. Type I herpes simplex virus can be isolated from genital sites
True False
d. Has an incubation period of 10-21 days
True False
True False
b. Has an incubation period of 3-6 months
True False
c. Can be cultured in vitro
True False
d. Is vertically transmissible
True False
True False
b. Anti-HBs antibody is detectable before jaundice develops
True False
c. The presence of HBeAg indicates that the infection has been cleared
True False
d. Detection of HBsAg may indicate previous immunisation
True False
a. Acute gingivostomatitis
True False
b. Cold sores
True False
c. Cervical warts
True False
d. Meningoencephalitis
True False
a. Is sensitive to acyclovir
True False
b. The majority of infections are associated with clinical disease
True False
c. Chronic carriage is associated with persistence of anti-HBs IgG
True False
d. Causes more severe disease in pregnancy
True False
Question 7: Cytomegalovirus
a. Causes hepatitis
True False
b. Is found in 1% of all neonates
True False
c. Is a recognised cause of fetal congenital anomalies
True False
d. Is not present in breast milk
True False
True False
b. Hepatomegaly
True False
c. Excessive production of growth hormone
True False
d. Cataract
True False
Question 9: Cytomegalovirus
True False
b. Causes post-auricular and sub-occipital lymphadenopathy
True False
c. Primary infection occurs in 0.2% of pregnant women
True False
d. Is the most common congenital infection
True False
True False
b. Sero-conversion occurs within 6 weeks of infection
True False
c. Needle stick injury involving an infected patient carries a 10% risk of transmitting the infection
True False
d. Risk of infection following needle stick injury is higher than for hepatitis B virus
True False
True False
b. Is not sexually transmissible
True False
c. Is associated with oral carcinoma
True False
d. Is sensitive to acyclovir
True False
True False
b. Infection is treated with famcyclovir
True False
c. Is spread by droplet infection
True False
d. Vaccination is necessary only in females
True False
a. Is a retro-virus
True False
b. Contains DNA
True False
c. Infects CD4 positive cells only
True False
d. Can be transmitted by breastfeeding
True False
True False
b. Remains dormant within the host, causing re-infection
True False
c. Is excreted for up to 7 days after infection
True False
d. Causes severe disease in transplant patients
True False
a. Is a DNA virus
True False
b. Is spread by the feco-oral route
True False
c. Is not vertically transmissible
True False
d. Is associated with chronic carriage
True False
Question 1: Vibrio cholerae
True False
b. Produces an exotoxin
True False
c. Is distinguishable from coliforms by gram staining
True False
d. Is sensitive to trtracycline
True False
Question 2: Streptococci
True False
b. Are anaerobic
True False
c. Have a capsule
True False
d. Can be cultured on blood agar
True False
Question 3: CLOSTRIDIA
True False
b. Are non-spore-forming
True False
c. Are readily killed by boiling water or chemical disinfectants
True False
d. Are commonly found in the environment
True False
True False
b. Is sensitive to penicillin
True False
c. Infection is treated with gentamicin
True False
d. Is resistant to erythromycin
True False
Question 5: Staphylococci
True False
b. Coagulase positive cocci produce a clot when mixed with plasma
True False
c. S. aureus is coagulase negative
True False
d. Produce penicliinnase (beta-lactamase)
True False
a. Is a snail
True False
b. Is prevalent in China
True False
c. Causes chronic granulomatous lesions
True False
d. Infestation predisposes to cancer
True False
Question 7: Endotoxins
a. Are polypeptides
True False
b. Are released by living bacteria
True False
c. Act non-specifically on the reticulo-endothelial system
True False
d. Are converted into non-toxic toxoids by formalin
True False
a. Is gram positive
True False
b. Is anaerobic
True False
c. Is non-spore forming
True False
d. Is capsulated
True False
a. Is a rickettsia
True False
b. Forms yellow granules in pus
True False
c. Is a commensal in the mouth
True False
d. Is a commensal in the vagina
True False
True False
b. Are converted into non-toxic toxoids by formaline
True False
c. Act at specific target sites
True False
d. Are highly antigenic
True False
True False
b. Alpha-haemolytic streptococci are differentiated by Lancefield grouping
True False
c. Lancefield group B streptococci are usually isolated from the vagina
True False
d. Lancefield group B streptococci are a recognised cause of neonatal septicaemia and
meningitis
True False
True False
b. Salmonella typhi may be found permanently in the biliary tract of carriers
True False
c. Klebsiella is characteristically sensitive to ampicillin
True False
d. Coliforms are facultative anaerobes
True False
True False
b. Grow in aerobic culture
True False
c. Are synergistic with coliforms
True False
d. Are typically resistant to penicillin
True False
True False
b. E. coli is lactose fermenting
True False
c. Klebsiella is non-lactose fermenting
True False
d. Salmonella and shigella are lactose fermenting
True False
True False
b. Ferments glucose and maltose
True False
c. Produces an endotoxin
True False
d. Is sensitive to penicillin
True False
Question 1: The following are recognised treatment for gonococcal infection
a. Penicillin + probenecid
True False
b. Doxycycline
True False
c. Azythromycin
True False
d. Spectinomycin
True False
a. Are intracellular
True False
b. Infect squamous cells
True False
c. Are found in birds
True False
d. Cause trachoma
True False
True False
b. Can be detected by culture of high vaginal swabs on blood agar
True False
c. Is an intracellular organism
True False
d. Produces infectious particles called elementary bodies
True False
True False
b. Causes an inflammation of the vaginal skin
True False
c. Is characterised by a positive amine test
True False
d. Is associated with candida albicans infection
True False
True False
b. Forms pseudohyphae
True False
c. Reproduces by budding
True False
d. Is associated with diabetes mellitus
True False
True False
b. Is transmitted to humans from cats
True False
c. Is transmitted to humans from rats
True False
d. Infection is usually via skin
True False
a. Is sensitive to penicillin
True False
b. Is sensitive to erythromycin
True False
c. Is sensitive to tetracycline
True False
d. Treatment may result in the Jarisch-Herxheimer reaction
True False
True False
b. The vaginal pH is < 4.5
True False
c. Is characterised by clue cells on wet vaginal smear
True False
d. Is associated with an increased number of lactobacilli in the vaginal flora
True False
Question 9: The following are recognised causes of a biological false positive serological test for
syphilis
a. Drug addiction
True False
b. Leprosy
True False
c. Recent malaria infection
True False
d. Recent immunisation
True False
a. Is a riskettsial infection
True False
b. Is caused by a gram negative cocobacillus
True False
c. Is frequently transmitted to man from inanimate objects
True False
d. Is transmitted in pasteurised cow?s milk
True False
Question 11: The following are recognised consequences of Chlamydia trachomatis infection
a. Interstitial pneumonitis
True False
b. Infertility
True False
c. Cervical intra-epithelial neoplasia
True False
d. Bartholinitis
True False
True False
b. Infection of the vagina can be treated with topical co-trimoxazole
True False
c. Is commonly isolated from the vagina in post-menopausal women
True False
d. Is commonly isolated from the vagina in pre-pubertal girls
True False
True False
b. Can be detected using the polymerase chain reaction on early morning urine specimens
True False
c. Can be detected by the ELISA test on endocervical swabs
True False
d. Infection can reliably be diagnosed by the Chlamydia antibody test
True False
a. Is gram positive
True False
b. Is a commensal in the bowel
True False
c. Is sensitive to miconazole
True False
d. Causes secondary infection after treatment with broad spectrum antibiotics
True False
Question 15: The following are recognised consequences of Chlamydia trachomatis infection
a. Conjunctivitis
True False
b. Fitz-Hugh-Curtis syndrome
True False
c. Cervicitis
True False
d. Vaginitis
True False
Question 1: The following are effective disinfectants for use on the skin
a. Isopropyl alcohol
True False
b. Chlorhexidine
True False
c. Formaldehyde
True False
d. Benzalkonium chloride
True False
True False
b. Nystatin ? inhibit fungal DNA synthesis
True False
c. Flucytosine ? inhibit fungal DNA synthesis
True False
d. Griseofulvin ? bind ergosterol, producing leakage of cellular contents
True False
Question 3: The following anti-viral agents are effective against the viruses listed
True False
b. Acyclovir ? varicella zoster virus
True False
c. Acyclovir ? cytomegalovirus
True False
d. Acyclovir ? Epstein-Barr virus
True False
a. Include erythromycin
True False
b. Include gentamicin
True False
c. Include azithromycin and clarithromycin
True False
d. Include clindamycin
True False
Question 5: Tetracyclines
True False
b. Are not active against intracellular bacteria
True False
c. Are excreted via the liver
True False
d. Are poorly absorbed from the gut
True False
Question 6: Tetracyclines
True False
b. Are effective against mycoplasma infections
True False
c. Do not cross the placenta
True False
d. Are contra-indicated in women of child-bearing age
True False
True False
b. Inhibit bacterial cell wall synthesis
True False
c. Are derivatives of p-aminobenzoic acid
True False
d. Inhibit the synthesis of tetrahydrofolic acid
True False
Question 8: The following are effective disinfectants for use on the skin
a. 100% alcohol
True False
b. 70% alcohol
True False
c. Iodine
True False
d. Mercuric chloride
True False
True False
b. Inhibit peptidoglycan formation
True False
c. Act within the cell membrane
True False
d. Are effective against gram negative bacilli
True False
Question 10: The following are target sites for the action of anti-bacterial agents
a. Exotoxin synthesis
True False
b. Nucleic acid synthesis
True False
c. Cell membrane function
True False
d. Amino acid transport
True False
Question 11: The following drugs are effective against Mycobacterium tuberculosis
a. Gentamicin
True False
b. Pyridoxine
True False
c. Pyrimethamine
True False
d. Streptomycin
True False
Question 12: The following are effective methods of sterilising surgical instruments
a. Pasteurisation
True False
b. Boiling
True False
c. Ethylene oxide
True False
d. Liquid glutaraldehyde
True False
True False
b. Are well absorbed from the gut
True False
c. Are excreted by the kidneys
True False
d. Are not effective against intracellular organisms
True False
Question 14: The following anti-viral agents are effective against the viruses listed
a. Ganciclovir ? cytomegalovirus
True False
b. Acyclovir ? HIV
True False
c. Foscarnet ? cytomegalovirus
True False
d. Zidovudine ? HIV
True False
True False
b. Ethambutol ? optic neuritis
True False
c. Rifampicin ? hypersensitivity reactions
True False
d. Rifampicin ? reduced visual acuity
True False
NORADRENALINE SYNTHESIS *****
• Noradrenaline to adrenaline
• Pupils - dilate *
1
• SKELETAL MUSCLE - tremor, glycolysis,
vasodilatation *
• Skin - sweating
• Electrolytes - hypokalaemia
• Hyperglycaemia
• Bronchospasm *
• Fatigue
• Sleep disturbance
METHYLDOPA *****
Side-effects
2
• Neuromuscular - myalgia, arthralgia, paraesthesia
• Oedema
3
CHOLINERGIC NEURONS
• Synthesize, store and release acetylcholine as their
neurotransmitter. Include:
NICOTINIC RECEPTORS
Nicotinic Agonists
• Acetylcholine
• Carbachol
• Nicotine
• Suxamethonium
1
EFFECTS - Skeletal muscle contraction followed by depolarising blockade of
neuromuscular transmission; indirect sympathetic and parasympathetic
effects by action at nicotinic receptors of autonomic ganglia
SUXAMETHONIUM *****
• Nicotinic agonist
NICOTINIC ANTAGONISTS
• Tubocurarine *
• Pancuronium
• Atracurium - useful in patients with hepatic / liver impairment as
inactivated by spontaneous dissociation
• Hexamethonium *
TUBOCURARINE *****
2
MUSCARINIC AGONISTS
• Methacholine
• Carbachol
• Pilocarpine
• Heart - bradycardia *
• Atropine *
• Hyoscine
• Tropicamide
• Ipratropium bromide
3
All competitive antagonists. There are at least three sub-types
of muscarinic receptors with Pirenzipine being a specific M1
antagonist (gastric parietal cells)
• Heart - tachycardia *
• Pupils - dilatation *
• Detrusor - relaxation *
• Tolterodine
4
• Flavoxate hydrochloride
• Propantheline bromide
• Propiverine hydrochloride
• Trosopium chloride
• Tricyclic antidepressants such as imipramine and amitriptyline
CHOLINESTERASE *****
• Found in blood
COMPETITIVE
• Neostigmine *
NON-COMPETITIVE
5
• Organophosphorus compounds are non-competitive
cholinesterase inhibitors - poisoning is treated with atropine and
pralidoxime
6
LOCAL ANAESTHETICS *****
Lignocaine, bupivacaine
Side-effects
• Circumoral paraesthaesia
• Respiratory failure
1
Lignocaine
2
INHALATION ANAESTHETICS *****
1
• THIOPENTONE SODIUM - barbiturate, narrow therapeutic
index, contraindicated in porphyria. No analgesic effects.
Highly alkaline (pH >10) and irritant if injection misplaced
(not suitable for im injection) *.
2
GLUCOCORTICOIDS *****
• Anti-inflammatory agents; enhance fetal lung maturity and reduce
perinatal mortality and morbidity when administered to the mother
24h to 7 days before pre-term delivery (up to 36 weeks gestation) *
SIDE-EFFECTS
1
7) Impaired wound healing, skin strophy, striae, acne *
ANTI-ANDROGENS *****
• Carbimazole, propylthiouracil *
• Not terratogenic; cross the placenta and enter breast milk. May cause
neonatal goitre / hypothyroidism therefore lowest effective dose should
be used and the neonata should be monitored *
2
HISTAMINE ANTAGONISTS *****
H1
H2
• Cimetidine, Ranitidine
• Tubocurarine *
• Vancomycin
• Atropine *
1
5HT ANTAGONISTS
ANTI-EMETICS *****
2
COMBINED ORAL CONTRACEPTIVE PILL *****
NORETHISTERONE *****
• 19-Nortestosterone derivative
• Active orally, has long half life and significant plasma concentrations
can be detected 1 month after a single 50mg dose
1
• Administered usually from days 2-6 of the cycle for ovulation
induction. Main use is ovulation induction in PCOS *
TAMOXIFEN *****
RALOXIFEN *****
• Oestrogen-antagonist in breast
2
TIBOLONE *****
3
BROMOCRIPTINE - DOPAMINE AGONISTS *****
• Ergot derivative
1
cause drug-induced Parkinsonism. They also cause tardive
dyskinesia
2
PROSTAGLANDINS *****
1
Question 1: Norethisterone
a. Is a steroid
True False
b. Is an oestrogen antagonist
True False
c. Is active when administered orally
True False
d. Decreases hypothalamic GnRH release
True False
Question 3: Tibolone
1
Question 4: Aspirin
Question 5: Tamoxifen
a. Is a steroid
True False
b. Is an oestrogen antagonist in breast tissue
True False
c. Is an oestrogen agonist in the post-menopausal uterus
True False
d. Is associated with an increased risk of venous thromboembolism
True False
a. Cimetidine
True False
b. Nandrolone
True False
c. Finasteride
True False
d. Flutamide
True False
2
Question 7: Raloxifen
a. Is a testosterone antagonist
True False
b. Inhibits spermatogenesis
True False
c. Is a progestogen
True False
d. Increases sebum production
True False
a. Muscle wasting
True False
b. Post-menopausal bleeding
True False
c. Peptic ulceration
True False
d. Amenorrhoea
True False
3
Question 10: The following drugs cause hyperprolactinaemia
a. Metoclopramide
True False
b. Bromocriptine
True False
c. Carbegolline
True False
d. Oestrogen
True False
a. Is anti-pyretic
True False
b. Inhibits uric acid excretion by the kidneys
True False
c. Inhibits platelet aggregation
True False
d. Inhibits prothrombin formation
True False
4
Question 13: With respect to drug therapy with glucocorticoids
5
HEPARIN *****
1
• Patients over 60 years of age, following similar doses of
heparin, may have higher plasma levels of heparin and
longer APTTs compared with patients under 60 years of
age.
WARFARIN *****
2
Therapy monitored by the prothrombin time. Severe
bleeding treated with clotting factors (FFP)
ANTI-PLATELET AGENTS
Aspirin / NSAIDs
ASPIRIN *****
Analgesic, anti-pyretic
3
DIGOXIN
• Cardiac glycoside
TOXICITY
• Cardiac arrhythmias
• Headache
• Myocardial depression
• Constipation / diarrhoea
• Rash
1
NITRATES
2
DIURETICS
• Protein-bound
POTASSIUM-SPARING DIURETICS*****
Amiloride, Triamterene, Spironolactone
All diuretics (apart from the potassium sparing diuretics) may cause hypokalaemia
and precipitate digoxin toxicity
1
Josejosejosejocase
Question 1: Heparin
a. Headache
True False
b. Hypertension
True False
c. Bradycardia
True False
d. Constipation
True False
1
Question 4: Heparin
Question 5: Heparin
a. Is a glycoprotein
True False
b. Occurs naturally in the body
True False
c. Crosses the placenta
True False
d. Is contra-indicated in breastfeeding women
True False
Question 6: Warfarin
2
Question 7: The following are characteristic of the diuretics listed
Question 9: Warfarin
3
Question 10: The following are recognised effects of beta-adrenergic
agonists
a. Hypertension
True False
b. Tachycardia
True False
c. Decreased cardiac output
True False
d. Increased gut motility
True False
a. Peripheral oedema
True False
b. Pre-mature closure of the ductus arteriosus
True False
c. Impotence
True False
d. Gynaecomastia
True False
4
a. Bendrofluazide ? effective anti-hypertensive agent (
True False
b. Bendrofluazide ? exacerbation of pre-existing diabetes mellitus
True False
c. Bendrofluazide ? site of action is the proximal convoluted tubule
True False
d. Bendrofluazide ? precipitation of digoxin toxicity
True False
a. Is an alpha-adrenergic antagonist
True False
b. Is contraindicated in diabetics
True False
c. Causes uterine smooth muscle relaxation
True False
d. Is contraindicated in asthmatics
True False
a. Tachycardia
True False
b. Hyperkalaemia
True False
c. Hypoglycaemia
True False
d. Hypertension
True False
5
BENZODIAZEPINES *****
• Absorbed orally
TRICYCLIC ANTIDEPRESSANTS
Side-Effects
1
1) ANTI-CHOLINERGIC - dry mouth, blurred vision, constipation, urinary
retention *
• Not terratogenic *
Side-Effects
Side-Effects
2
3) Impaired temperature regulation causing hypothermia / hyperthermia
Side-effects
3
DULOXETINE FOR URINARY STRESS INCONTINENCE
• The maximum duration of treatment in the trials was 12 weeks and the
age of women treated was 22 - 83 years
Side-effects
Contraindications
• Pregnancy, lactation
• Hepatic impairment
• Monoamine oxidase therapy
• Lowers seizure threshold therefore avoid in epilepsy
• Can enhance the anti-coagulant effects of warfarin
• Metabolised by the same enzymes as ciprofloxacin and fluvoxamine -
avoid co-prescription
• Avoid co-prescription with SSRIs and tricyclic anti-depressants
1
Role of duloxetine
2
OPIOID ANALGESICS *****
Side-Effects:
Morphine *****
• Increases the tone and decreases peristalsis. This increases gastric stasis
and causes constipation. *
1
• Cause histamine release - dilation of cutaneous blood vessels, with
resulting flushing of the face and neck, pruritus, and sweating.
• Only about 40% of the administered oral dose reaches the central
compartment because of first-pass metabolism in the gut and liver
• Crosses the placental membrane and has been found in breast milk *
PARACETAMOL *****
2
Quejosestion 1: The following are opioid drugs
a. Morphine
True False
b. Apomorphine
True False
c. Loperamide
True False
d. Codein phosphate
True False
a. Paclitaxel
True False
b. Carboplatin
True False
c. Ondansetron
True False
d. Domperidone
True False
a. These agents are used for induction but not for maintenance of
anaesthesia
True False
b. These agents can be administered with 5% oxygen
True False
c. Halothane is a volatile liquid at room temperature
True False
d. Diethyl ether is highly inflammable
True False
1
Question 4: With respect to inhalation anaesthetic agents
a. Oestrogen
True False
b. Metoclopramide
True False
c. Levodopa
True False
d. Cisplatin
True False
Question 6: Chlorpromazine
2
Question 7: Lignocaine
Question 9: Lignocaine
3
Question 10: With respect to intravenous anaesthetic agents
4
a. Therapy requires regular assessment of serum lithium concentrations
True False
b. Clearance and therefore therapeutic dose is decreased in pregnancy
True False
c. Toxicity is associated with hyporeflexia
True False
d. Causes polyuria and polydypsia
True False
a. Convulsion
True False
b. Respiratory failure
True False
c. Hypotension
True False
d. Ischaemic necrosis of digits
True False
5
DRUG INTERACTIONS
• Carbamazepine
• Ethanol
• Groseofulvin
• Phenobarbitone
• Phenytoin
• Rifampicin
These drugs will INCREASE the metabolism of drugs that are inactivated via
the MFO system (glucocorticoids, oral contraceptives, theophylline and
warfarin) and REDUCE their efficacy. Higher doses are therefore required to
attain the same therapeutic effect. *
1)Phenelzine
2)Cimetidine
3)Isoniazide
4)Sodium valproate
5)Sulphonamides
6)Erythromycin
7)Theophylline
Lead to impaired metabolism of drugs such as warfarin, increasing its activity.
1
C) METHOTREXATE INTERACTIONS *****
D) OTHER INTERACTIONS
E) ATYPICAL ACETYLATION
2
F) MALIGNANT HYPERTHERMIA
• Nalidixic acid
• Salicylic acid
• Sulphonamides
• Chloroquine
• Primaquine
3
I) DRUG INTERACTIONS - LITHIUM
• Anti-epileptics
• Anti-psychotics
• Bronchodilators
• Cardiac drugs
• Anti-parkinsonian agents
• Immunosuppressants
• Anti-glaucoma drugs
• Corticosteroids (additional cover may be required)
4
DRUGS THAT SHOULD BE DISCONTINUED *****
• Anti-coagulants
5
Question 1: The following drugs should be discontinued before general
anaesthesia for major elective surgery
a. Warfarin
True False
b. Nalidixic acid
True False
c. Salicylic acid
True False
d. Chloroquine
True False
1
Question 4: The following drugs reduce the efficacy of the combined
oral contraceptive pill
a. Nevirapine
True False
b. Prednisolone
True False
c. Modafinil
True False
d. Theophylline
True False
a. Stilboestrol
True False
b. Carbimazole
True False
c. Phenytoin
True False
d. Sodium valproate
True False
a. Metronidazole
True False
b. Warfarin
True False
c. Griseofulvin
True False
d. Disulfiram
True False
2
Question 7: The following drug interactions are correct
a. Aspirin
True False
b. Diclofenac
True False
c. Folic acid
True False
d. Sulphonamides
True False
a. Captopril
True False
b. Diclofenac
True False
c. Sodium bicarbonate
True False
d. Methyldopa
True False
3
Question 10: The following drugs inhibit hepatic mixed function oxidase
enzyme
a. Sodium valproate
True False
b. Phenytoin
True False
c. Isoniazide
True False
d. Erythromycin
True False
a. Tricyclic antidepressants
True False
b. Monoamine oxidase inhibitors
True False
c. Bronchodilators
True False
d. Immunosuppressive agents
True False
a. Frusemide
True False
b. Theophylline
True False
c. Probenecid
True False
d. Carbamazepine
True False
4
Question 13: The following drugs induce hepatic mixed function oxidase
enzyme
a. Cimetidine
True False
b. Isoniazide
True False
c. Phenobarbitone
True False
d. Rifampicin
True False
a. Cytotoxic drugs
True False
b. Isotrentinoin
True False
c. Heparin
True False
d. Warfarin
True False
Question 15: The following drugs increase the risk of ergotism when
used in combination with ergometrine
a. Azithromycin
True False
b. Nelfinavir
True False
c. Noradrenaline
True False
d. Oxytocin
True False
5
CHEMOTHERAPEUTIC AGENTS
• Methotrexate - S-phase
1
• Aactive orally
2
PLATINUM AGENTS *****
CISPLATIN
• Direct renal tubular toxin and renal damage is the major dose-
limiting toxicity and is associated with hypomagnesaemia. Renal
damage can be reduced by forced diuresis using saline or
mannitol or by administration in hypertonic saline.
CARBOPLATIN
1
TAXANES *****
PACLITAXEL
1
2
TOPOISOMERASE I INHIBITORS
TOPOTECAN
ANTIMETABOLITES *****
1
VINCA ALKALOIDS
VINCRISTINE / VINBLASTINE
2
AAaAaja
Question 1: Cyclophosphamide
a. Is an alkylating agent
True False
b. Causes amenorrhoea and oligospermia
True False
c. Is an anti-metabolite
True False
d. Is active only during the S phase of the cell cycle
True False
a. Methotrexate
True False
b. Vincristine
True False
c. Flurouracil
True False
d. Mercaptopurine
True False
a. Cisplatin
True False
b. Carboplatin
True False
c. Cyclophosphamide
True False
d. Doxorubicin
True False
1
Question 4: Methotrexate
a. Bradycardia
True False
b. Loss of eye-brows and axillary hair
True False
c. Hyper-sensitivity
True False
d. Neutropaenia
True False
Question 6: Paclitaxel
2
Question 7: The following drugs are alkylating agents
a. Ifosfamide
True False
b. Carboplatin
True False
c. Vincristine
True False
d. Etoposide
True False
Question 9: Cyclophosphamide
3
Question 10: Cis-platin
a. Is a pro-drug
True False
b. Causes acute haemorrhagic cystitis
True False
c. Is inactivated by the liver
True False
d. Is associated with an increased long-term risk of acute myeloid
leukaemia
True False
4
Question 13: Paclitaxel
a. Is a taxane
True False
b. Is a pro-drug
True False
c. Is protein-bound
True False
d. Is associated with hypersensitivity reactions
True False
5
Act at 4 main sites
• Protein synthesis
BACTERIAL RESISTANCE
CAUSED BY:
• Single gene mutations - random events, with the mutant that results in resistance being
selected in the presence of the antibiotic
• Transposons - 'jumping genes' - resistance genes that are capable of intergration into the
chromosome or plasmids
• Analogues of d-alanyl-d-alanine
• Effective against all gram positive bacteria and gram negative cocci
• Cycloserine - inhibits reactions incorporating alanine into cell wall precursor within the
cytoplasm
• Inhibit bacterial cell wall synthesis by binding to d-alanyl-d-alanine at the end of a pentapeptide
chain, preventing the incorporation of new subunits
• Large molecules which cannot penetrate gram negative cell wall. Only active against gram
positive bacteria
• Not absorbed from the GI tract. Oral administration used to treat Clostridium difficile diarrhoea
• Not absorbed from the GI tract.* Do not cross the blood-brain barrier
TETRACYCLINES *****
CHLORAMPHENICOL
MACROGLIDES *****
• Well absorbed from the gut; penetrate tissues well and are active
against intracellular organisms *
CLINDAMYCIN *****
ANTI-VIRAL AGENTS
• Zidovudine- HIV
listeria monocytogenes: 3
T Can grow at 6c. A
F Is gut commensal B
F Is a gram-negative bacillus C
F Infection is best treated with benzylpenicillin D
T Is a cause of septicaemia in neonates E
Metronidazole: 4
T Is effective against giardia lamblia A
T Is effective when administered per rectum B
F Should not be administered intravenously C
T Is usually effective against entamoeba histolytica D
T Interferes with ethanol metabolism E
Metronidazole: 5
F Is a folic acid antagonist A
F Is ineffective when given per rectum B
F Should not be administered intravenously C
T Is effective against Entamoeba histolytica D
T Interferes with ethanol metabolism E
Gentamicin: 6
T Is ineffective systemically when given by mouth A
F Is metabolized prior to excretion by the kidney B
T May cause damage to the eighth cranial nerve C
T Is a bacteriostatic drug D
T Toxicity is potentiated by frusemide E
Co-trimoxazole: 7
T Contains two different drugs. A
T Inhibits folic acid synthesis. B
T Potentiates the action of warfarin. C
F Is bacteriostatic D
T Displaces methotrexate from protein binding sites. E
Comments 2:
Combination of sulphonamide and trimethorpim, with synergistic
bactericidal effect through inhibition of folic acid synthesis. It
potentiates the effects of warfarin (like erythromycin, isoniazid) and
the sulphonamide component can displace methotrexate from its
plasma protein binding site.+
The following substances are sympathomimetic amines: 8
T Amphetamines A
T Ephedrine B
F Histamine C
T Isoprenaline D
F Chlorpromazine E
Concerning heparins: 21
T Heparin is synthesized in the lungs A
T Antithrombin III is necessary for standard heparins to exert their
anticoagulant effect B
T Factor X is inhibited by low-molecular-weight heparins C
T Low-molecular-weight heparins have a longer half-life than
standard heparins D
T Penicillins potentiate the action of low-molecular-weight heparins
E
Propanolol: 25
F Is a selective beta adrenergic blocking agent A
F Is not secreted in breast milk B
T Given in pregnancy slows the maternal heart rate C
T Causes bad dreams D
T Antagonises the tocolytic effect of salbutamol E
Clomifene citrate: 47
F Is an anti-androgen A
T Does not stimulate ovulation directly B
T Can produce visual disturbances C
T Is generally prescribed throughout the proliferative phase of the
menstrual cycle D
T In the treatment of an ovulation, increases the risk of multiple
pregnancy E
Cyproterone acetate 48
F Is an oestrogen A
F Is used for the treatment of amenorrhea B
T Bind to androgen receptors C
F Increases libido D
T Inhibits spermatogensis E
The following are cytotoxic alkylating agents 49
T Cyclophosphamide A
F Mercaptopuracil B
T Chloroambucil C
F Fluorouracil D
F Methotrexate E
a. Isopropyl alcohol
True False
b. Chlorhexidine
True False
c. Formaldehyde
True False
d. Benzalkonium chloride
True False
True False
b. Nystatin ? inhibit fungal DNA synthesis
True False
c. Flucytosine ? inhibit fungal DNA synthesis
True False
d. Griseofulvin ? bind ergosterol, producing leakage of cellular contents
True False
Question 3: The following anti-viral agents are effective against the viruses listed
True False
b. Acyclovir ? varicella zoster virus
True False
c. Acyclovir ? cytomegalovirus
True False
d. Acyclovir ? Epstein-Barr virus
True False
a. Include erythromycin
True False
b. Include gentamicin
True False
c. Include azithromycin and clarithromycin
True False
d. Include clindamycin
True False
Question 5: Tetracyclines
True False
b. Are not active against intracellular bacteria
True False
c. Are excreted via the liver
True False
d. Are poorly absorbed from the gut
True False
Question 6: Tetracyclines
True False
b. Are effective against mycoplasma infections
True False
c. Do not cross the placenta
True False
d. Are contra-indicated in women of child-bearing age
True False
True False
b. Inhibit bacterial cell wall synthesis
True False
c. Are derivatives of p-aminobenzoic acid
True False
d. Inhibit the synthesis of tetrahydrofolic acid
True False
Question 8: The following are effective disinfectants for use on the skin
a. 100% alcohol
True False
b. 70% alcohol
True False
c. Iodine
True False
d. Mercuric chloride
True False
True False
b. Inhibit peptidoglycan formation
True False
c. Act within the cell membrane
True False
d. Are effective against gram negative bacilli
True False
Question 10: The following are target sites for the action of anti-bacterial agents
a. Exotoxin synthesis
True False
b. Nucleic acid synthesis
True False
c. Cell membrane function
True False
d. Amino acid transport
True False
Question 11: The following drugs are effective against Mycobacterium tuberculosis
a. Gentamicin
True False
b. Pyridoxine
True False
c. Pyrimethamine
True False
d. Streptomycin
True False
Question 12: The following are effective methods of sterilising surgical instruments
a. Pasteurisation
True False
b. Boiling
True False
c. Ethylene oxide
True False
d. Liquid glutaraldehyde
True False
True False
b. Are well absorbed from the gut
True False
c. Are excreted by the kidneys
True False
d. Are not effective against intracellular organisms
True False
Question 14: The following anti-viral agents are effective against the viruses listed
a. Ganciclovir ? cytomegalovirus
True False
b. Acyclovir ? HIV
True False
c. Foscarnet ? cytomegalovirus
True False
d. Zidovudine ? HIV
True False
True False
b. Ethambutol ? optic neuritis
True False
c. Rifampicin ? hypersensitivity reactions
True False
d. Rifampicin ? reduced visual acuity
True False
SULPHONAMIDES *****
TRIMETHOPRIM *****
QUINOLONES *****
• Streptomycin
Rifampicin
METRONIDAZOLE *****
• A nitroimidazole
NITROFURANTOIN
Question 1: Tubocurarine
a. Urinary retention
True False
b. Palpitations
True False
c. Skeletal muscle weakness
True False
d. Urge incontinence
True False
1
Question 4: Muscarinic antagonists have the following effects on the
organs / tissues described
a. Pupils ? dilatation
True False
b. Ciliary muscles ? contraction
True False
c. Lacrimal glands ? increased secretion
True False
d. Salivary glands ? decreased secretion
True False
a. Atropine
True False
b. Carbachol
True False
c. Pilocarpine
True False
d. Hyoscine
True False
a. Tropicamide
True False
b. Ipratropium bromide
True False
c. Benzhexol
True False
d. Tubocurarine
True False
2
Question 7: With respect to Cholinesterase
a. Oxybutynin
True False
b. Tolterodine
True False
c. Imipramine
True False
d. Amitriptyline
True False
3
Question 10: Muscarinic agonists have the following effects on the
organs / tissues listed
a. Is a muscarinic agonist
True False
b. Causes skeletal muscle fasciculation on intravenous administration
True False
c. Causes depolarisation blockade of neuromuscular transmission
True False
d. Causes prolonged loss of consciousness in patients with
cholinesterase deficiency
True False
a. Heart ? tachycardia
True False
b. Respiratory tract ? increased bronchial secretions
True False
c. Respiratory tract ? smooth muscle relaxation
True False
d. Gut ? decreased motility
True False
4
inhibitors
a. Neostigmine
True False
b. Benxhexol
True False
c. Malaoxon
True False
d. Edrophonium
True False
a. Constipation
True False
b. Blurred vision
True False
c. Increased sweating
True False
d. Dry mouth
True False
a. Carbachol
True False
b. Suxamethonium
True False
c. Atropine
True False
d. Tubocurarine
True False
5
TYPES OF DATA *****
• Intervals between adjacent scale values are equal with respect the
attribute being measured - the difference between 8 and 9 is the
same as the difference between 80 and 81
• There is a rational zero point for the scale - zero actually means
none
• Confidence intervals *
Mean + 2(standard error) and mean - 2(standard error) give the range
which has a 95% chance of including the population mean = 95%
confidence interval
Bffxfrytdfytthpae[\pirtrtyo
• Family of distributions with the same general shape.
• The distribution is defined by two parameters: the mean (μ) and the
standard deviation (σ). If these are known then one knows essentially
as much as if one had access to all the data *
• 68% of the data fall within 1 standard deviation of the mean (34%
above and 34% below) *
• 95% of the data fall within 2 (1.96) standard deviations of the mean *
• 99.7% of the data falls within 3 standard deviations (SD)of the mean *
Parametric Tests *
Assumption
Examples include:
• Independent t-test
Non-Parametric Tests *
• Data with a low P value (less than or equal to 0.05) are said to be
statistically significant. p = 0.05 means that there is a 1 in 20 chance
that the data is the result of random chance *
• Odds *- a ratio of the probability that an event will occur versus the
probability that the event will not occur = probability / (1-probability).
• For example, if you draw cards and have 3 spades and 1 diamond,
then the odds of drawing a diamond = [(1/4)/ (3/4)] = 1/3 = 0.33.
• This differs from risk (or probability): the risk drawing a diamond =
• Odds ratio *- the ratio of odds - the ratio of the odds of an event
occurring in the exposed group versus the unexposed group.
• When the primary outcome is rare, relative risk and odds ratio are ~
equal.
• Odds ratio and relative risks are presented with 95% confidence
intervals, for instance, relative risk (RR = 2.5; 95% CI 0.6 to 4.4)
• When the 95% CI of the odds ratio or relative risk includes 1 (as above)
then the groups are NOT statistically significantly different (p > 0.05)
TYPES OF STUDIES *****
True False
b. The Chi squared test may be used when data are not normally distributed
True False
c. In a distribution that is skewed to the right, the mean is less than the median
True False
d. In a distribution that is skewed to the right, the mean lies to the left of the median
True False
True False
b. The incidence of a disease is the proportion of the population suffering from the disease at any
one time
True False
c. The mode is always greater than the mean in a normal distribution
True False
d. P = 0.001 indicates that the observation is more likely to have occurred by chance compared to
p = 0.05
True False
True False
b. The median always lies at the mid-point of the range
True False
c. The standard deviation is always greater than the standard error of the mean
True False
d. There are the same number of observations greater than and less than the median
True False
True False
b. Sensitivity is equal to positive predictive value
True False
c. The 95% confidence intervals must cross 1 to prove statistical significance
True False
d. An odds ratio of 1:4 means a risk of 25%
True False
True False
c. Is a test of statistical significance
True False
d. Is expressed as the square of the original units
True False
Question 6: In a randomised double-blind trial of two cholesterol lowering drugs, 400 patients
received drug A and 398 received drug B. Drug A was found to cause a greater reduction in
serum cholesterol (p = 0.001).
True False
b. Randomisation controls for unknown confounding variables
True False
c. Randomisation controls for known confounding variables
True False
d. It is likely that the patients receiving drug A had different characteristics from those receiving
drug B
True False
Question 7: In a sample of 1000 pregnant women, birth weight was found to be normally
distributed with a mean of 3.2kg and a standard deviation of 600g
a. 95% of babies will have birth weights between 2.0 and 4.4kg
True False
b. The standard error for birth weight can be calculated from 3.2 divided by the square root of
1000
True False
c. The variance for birth weight would be 36kg squared
True False
d. The standard error of the mean is independent of the sample size
True False
True False
b. Has a variance which is measured in units squared
True False
c. Kurtosis = 0
True False
d. 2.5% of the values in the sample lie more than 2SD below the mean
True False
a. Each subject will take either the drug or placebo but not both
True False
b. The subjects can choose whether they take the drug or placebo
True False
c. The investigator decides which subject takes the drug or the placebo
True False
d. The likelihood of the trial giving statistically significant results is independent of the number of
subjects
True False
Question 10: In a randomised double-blind trial of two cholesterol lowering drugs, 400 patients
received drug A and 398 received drug B. Drug A was found to cause a greater reduction in
serum cholesterol (p = 0.001).
a. The data should have been analysed by non-parametric tests if they are not normally
distributed
True False
b. The results reach an acceptable level of statistical significance
True False
c. Unequal numbers in the two groups invalidate the trial
True False
d. Drug A has been shown to be 1000 times more effective than drug B
True False
True False
b. Includes all fetuses and infants of gestation age more than 20 weeks
True False
c. Is expressed as deaths per 1000 live births
True False
d. Includes deaths occurring in the first month of life
True False
Question 12: The following conditions must be met before parametric tests can be used
True False
b. Data are normally distributed
True False
c. The variance of the groups is very different
True False
d. The data are from a randomised study
True False
a. The 95% confidence interval indicates the range within which 19 out of 20 values will lie
True False
b. The p value indicates how often a result will occur by chance
True False
c. The conventionally accepted level of statistical significance is p < 0.05
True False
d. A relative risk of 0.5 is statistically significant irrespective of the 95% confidence interval
True False
True False
b. May be used to estimate the range of the distribution
True False
c. Is a measure of the scatter
True False
d. Is an estimate of skewness
True False
Question 15: In a randomised double-blind trial of two cholesterol lowering drugs, 400 patients
received drug A and 398 received drug B. Drug A was found to cause a greater reduction in
serum cholesterol (p = 0.001).
True False
b. Randomisation has been unsuccessful because there is an unequal number of patients in the
two groups
True False
c. Randomisation may be undertaken using the date of birth of the patients
True False
d. A computer based random number generator may be used for randomisation
True False