Pre clinical Subjects COACHING DAILY SUBJECT REAL TEST HIGH YIELD

PROGRAM MOCK WISE SERIES MATERIALS

HOURS EXAM MOCK
EXAM
1 Anatomy+Histology+Embryology 32 YES Total AIIMS -5 HIGH YIELD
2 Physiology 28 YES Number of AIPGMEE- SUBJECT
3 Biochemistry + Genetics 28 YES Mock 5 WISE
4 Microbiology + Immunology 32 YES Exams PGI-4 MATERIALS
5 Pathology 30 YES PREPARED
6 Preventive & Social medicine 30 YES 15 EXAMS BY AGM
7 Pharmacology 28 YES ADrPlexus
8 Radiology & Radio-therapeutics 16 YES TEAM
9 PSM 32 YES

10 Internal medicine 46 YES ONLINE AIIMS -5 HIGH YIELD

11 Surgery 32 YES MCQ TEST AIPGMEE- SUBJECT
12 Traumatology & Orthopedics 12 YES 19 TESTS 5 WISE
13 Obs & Gynec 32 YES PGI-4 MATERIALS
14 Pediatrics 16 YES PREPARED
15 Ophthalmology 20 YES BY AGM
16 ENT 16 YES ADrPlexus
17 Anesthesia & Emergency med 12 YES TEAM
18 Psychiatry 12 YES
19 Dermatology 12 YES

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ADrPlexus AGM- SYNAPSE WITH US FOR SUCCESS Anatomy Simplified
2011

Anatomy of Abdomen
Boundaries of the abdomen:
1. Superior boundary: the diaphragm
2. Inferior boundary: pelvic cavity; the plane running through the pubic symphysis, along the iliopectineal line, and across
the ala and promontory of the sacrum defines the inferior boundary of the abdomen
3. Posteriorly: the sacrum, pelvic bones, and the sacroiliac joints (near the ala of the sacrum)
4. Anteriorly: the pelvic bones articulating at the symphysis pubis
5. Laterally: the pubic crests, pubic tubercles and the pectineal lines

Osseous landmarks:
Iliac crests: their highest points are near the
area of the spine of the L4 vertebra (an
important region when performing spinal
taps)
Umbilicus: generally lies in the T10
dermatome and marks the level of the
intervertebral disk between L3 and L4
Xiphoid process of the sternum: linea alba
extends from here
Fused cartilages of ribs 7-10
Floating ribs 11 and 12
Pubic symphysis
Pubic bones
Iliac spines and crests

Ligaments associated with the abdomen:

o Inguinal Ligament: part of the lower free margin of the aponeurosis of the external oblique muscle; extends from the
anterior superior iliac spine to the pubic tubercle; attaches to fascia lata of thigh
o Lacunar Ligament: runs between inguinal ligament and pectineal line; forms medial part of floor of inguinal canal
o Pectineal Ligament: runs along pectineal line of pelvis; separates pelvic and abdominal cavities
o Interfoveolar Ligament: medial thickening of transversalis fascia at deep inguinal ring
o Umbilical ligaments: remnants of the umbilical arteries
o Median umbilical ligament: remnant of the urachus

Fascia layers:
A). Superficial Fascia - divided into two layers:
i. Superficial fatty layer (Campers Fascia) contains
adipose tissue and fuses with superficial fascia of thigh;
cannot be used to suture
ii. Deep membranous layer (Scarpas Fascia) is more
fibrous and contains very little adipose tissue; fuses with
deep fascia at the inguinal ligament; continuous with the
fascia lata of the thigh and with Colles fascia (the superficial fascia of the perineum); better suturing
material
B). Deep Fascia - thin layer over superficial abdominal muscles (epimysium); cannot be separated
C). Transversalis Fascia - lines most of abdominal wall; covers posterior surface of transversus abdominis muscle
and aponeurosis; extends into thigh to form part of femoral sheath; forms part of covering (internal spermatic
fascia) of spermatic cord
D). Just inside the transversalis fascia is the parietal peritoneum, a thin membrane which is separated from the
transversalis fascia by endoabdominal (extraperitoneal) fat

Muscular Layers:
Flat (lateral) Muscles - aid in rotation and lateral flexion of trunk to same side; protect viscera and increase intra-
abdominal pressure. The muscles become aponeurotic sheets as they approach the midline before fusing at the linea
alba.

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I. External Obliques - arise from lower eight ribs (5-12); fibers run downward and medially (like external
intercostal muscles); part of aponeurosis forms inguinal ligament; forms part of anterior portion of rectus
sheath
II. Internal Obliques - arise from ribs 10-12, the thoracolumbar fascia, part of iliac crest, and a portion of the
inguinal ligament; upper fibers run upwards and medially; intermediate fibers form part of rectus sheath
before joining linea alba; lower fibers attach to pectineal line with fibers from transversus abdominis muscle
forming conjoint tendon
III. Transversus Abdominis - arise from costal cartilages 7-12, the thoracolumbar fascia, part of iliac crest, and
portion of inguinal ligament; fibers run transversely to linea alba; lower fibers attach to pectineal line with
internal obliques via the conjoint tendon.
Vertical Muscles - flex trunk against gravity; also protect viscera and increase intra-abdominal pressure
I. Rectus Abdominis - vertical muscle fibers on either side of linea alba; broad superiorly and more narrow
inferiorly; attachments at costal cartilages 5-7, the pubic crests, and the symphysis pubis; separated into
segments by three tendinous inscriptions (one at level of umbilicus, 2 above umbilicus); lateral borders defined
by linea semilunaris
II. Pyrimidalis - small triangular muscle covering lower fibers of rectus abdominis that ; no known function

Rectus Sheath:
I. The rectus sheath encloses the rectus
abdominis muscles, the pyrimidalis
muscles, and the superior/inferior
epigastric arteries/veins.
II. The aponeurosis of the external oblique
muscles always contribute to the anterior
sheath
III. Above the costal margin, the sheath
(anterior to posterior) is composed of
external oblique aponeurosis, rectus
muscle, and costal cartilage
IV. The arcuate line is an important landmark
approximately halfway between the
umbilicus and the symphysis pubis. The arcuate line is the point at which the posterior part of the rectus sheath is
formed superiorly by aponeuroses and inferiorly by transversalis fascia.
V. B/ the arcuate line and the costal margin, the aponeurosis of the internal oblique muscle splits around the rectus
abdominis muscle, contributing to both the anterior and posterior rectus sheath; in this region.
a. The sheath is (anterior to posterior) external oblique aponeurosis, half of internal oblique aponeurosis,
rectus muscle, half of internal oblique aponeurosis, transversus abdominis aponeurosis
VI. Below the arcuate line, the aponeurosis of the internal oblique passes only anterior to the rectus abdominis,
forming only the anterior portion of the rectus sheath.
a. In this region, the sheath is (anterior to posterior) external oblique aponeurosis, internal oblique
aponeurosis, transversus abdominis aponeurosis, rectus muscle, transversalis fascia
VII. The aponeurosis of the transversus abdominis muscle forms the posterior rectus sheath above the arcuate line and
forms part of the anterior sheath below the arcuate line; below the arcuate line, the posterior rectus sheath is
formed by the transversalis fascia.

Surgical Incision
Above the arcuate line: Below the arcuate line:
skin skin
superficial fascia (Campers and Scarpas) superficial fascia
deep fascia deep fascia
external oblique aponeurosis external oblique aponeurosis
internal oblique aponeurosis internal oblique aponeurosis
rectus abdominis muscle transversus abdominis aponeuros
internal oblique aponeurosis pyrimidalis muscle in inferior
transversus abdominis aponeurosis rectus abdominis muscle
transversalis fascia transversalis fascia
peritoneum peritoneum

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ADrPlexus AGM- SYNAPSE WITH US FOR SUCCESS Anatomy Simplified
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Dermatomes:
I. The abdominal wall is divided into horizontal dermatomes supplied by ventral rami of spinal nerves.
II. T7, T8, T9 innervate the skin superior to umbilicus.
III. T10 innervates the skin around the umbilicus.
IV. T11, subcostal nerve (T12), iliohypogastric nerve (L1), and the ilioinguinal nerve (L1) supply the skin inferior to the
umbilicus.

Nerve organization:
I. Lateral cutaneous branches innervate the lateral
portions of the abdomen while anterior
cutaneous branches innervate the midline
II. Muscles of the abdomen are also innervated by
the 7th through 12th intercostal nerves which
run between the internal oblique and
transversus abdominis along the neurovascular
plane
III. Nerves actually pierce the rectus sheath
(arteries do not)
IV. L1 nerve splits to iliohypogastric and ilioinguinal
nerves which innervate the lower internal
oblique and transversus abdominis
V. This is very similar to the organization of the thoracic cutaneous nerves.
VI. Relationship of nerves to muscle layers: pierce the rectus sheath a short distance from the median plane after the
rectus muscle has been supplied and lie superficial to muscular layer.

Vascular organization (arteries and veins):

I. Generally organized in the vertical direction.
II. Different from thoracic wall, which has horizontal vessels from vertical vessels.
III. Veins drain into the azygos system.
th th
IV. 10 , 11 posterior intercostals, subcostal arteries: lie superficial to transversus abdominis and deep to rectus
abdominis
V. Internal thoracics (branch of subclavian) branches into
a. Musculophrenics gives off the 7th through 9th intercostal arteries; these along with the lumbar arteries
supply the lateral portion of the abdomen
b. Superior epigastrics direct continuation of the internal thoracic and enter the rectus sheath its posterior
layer to supply the upper part of the rectus abdominis. Artery anastomoses with the inferior epigastric
artery.
VI. External iliacs:
a. Inferior epigastrics: Arises from the external iliacs just proximal to its passage under the inguinal ligament.
Runs superiorly in the transversalis fascia to enter the rectus sheath inferior to the arcuate line. Its
branches enter the lower rectus abdominis and anastomose with the superior epigastric artery around the
umbilicus.
b. Deep circumflex iliacs: runs on deep aspect of anterior abdominal wall, parallel to inguinal ligament
VII. Femoral artery and great saphenous vein:
a. Superficial circumflex iliacs: runs in superficial fascia along inguinal ligament
b. Superficial epigastrics: runs in superficial fascia toward umbilicus
th th
VIII. Anterior and collateral branches of the posterior intercostal vessels in 10 and 11 spaces
IX. Anterior branches of subcostal arteries and veins
X. Branches of the musculophrenic vessels from internal thoracic
arteries and veins

Inguinal canal:
A. Oblique, inferomedially directed passage through the
inferior part of anterior abdominal wall.
B. Lies parallel and just superior to the medial half of the
inguinal ligament.
C. Spermatic cord in males and round ligament of uterus

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in females. Also contains blood, lymphatic vessels, and ilioinguinal nerve in both sexes.
D. From deep inguinal ring to superficial inguinal ring.
I. Superficial inguinal ring Exit from the inguinal canal above the pubic tubercle; ring created by splitting of external
oblique fiber/aponeurosis
a. Bordered by the lateral and medial crura; base formed by
pubic crest
b. Spermatic cord and/or round ligament of uterus exit
inguinal canal through this ring.
II. Deep inguinal ring Entrance to the inguinal canal and formed by
outpouching of the transversalis fascia (sometimes thickened to form
interfoveolar ligament)
a. The ductus deferens, testicular arteries and veins, and the
genital branch of the genitofemoral nerve pass through the
deep inguinal ring
III. Boundaries:
a. Anterior wall formed by external oblique aponeurosis
throughout the length of the canal with the anterior wall of the lateral part of the canal being reinforced
by fibers of internal oblique
b. Posterior wall formed by transversalis fascia with medial part reinforced by merging of pubic
attachments of the internal oblique and transverse abdominis aponeuroses into the conjoint tendon
c. Roof formed by arching fibers of internal oblique and transverse abdominal muscles
d. Floor formed by superior surface of the inguinal ligament and an infolding of the thickened inferior
border of the external oblique aponeurosis; the most medial part
of the floor is formed by part of the inguinal ligament that
attaches to the superior pubic ramus as the lacunar ligament
rather than attaching to the pubic tubercle.

IV. Muscular components of inguinal canal

a. Anterior wall
i. External oblique aponeurosis:
ii. Internal oblique: reinforces anterior wall of lateral part of canal
b. Posterior wall
i. Transversalis fascia
ii. Internal oblique & transverse abdominal aponeurosis (join to form conjoint tendon)
c. Roof: Internal oblique and transverse abdominis muscles
d. Floor: superior surface of inguinal ligament & lacunar ligament
V. Ligaments of inguinal canal
a. Inguinal ligament
b. Lacunar ligament
VI. Inguinal Ring
a. Deep (internal ring): entrance to inguinal canaloutpouching of transversalis fascia; lies superior to
middle of inguinal ligament, lateral to inferior epigastric vessels
b. Superficial external inguinal ring: exit from inguinal canal; opening between aponeurosis of external
oblique (superolateral to pubic tubercle)
c. Lateral & medial margins of ring: lateral & medial crura
VII. Surface projections of inguinal canal:
a. Oblique inferomedially directed passage through the inferior part of anterior abdominal wall
b. Contains spermatic cord or round ligament of uterus and also ilioinguinal nerve (both sexes)
VIII. Surface projections of bony pelvis

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ADrPlexus AGM- SYNAPSE WITH US FOR SUCCESS Anatomy Simplified
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a. Iliac crest
b. Anterior & Posterior superior iliac spine
c. Iliac tubercle
IX. Pubic tubercle & Pubic crest

Testicular descent:
I. Embryologically, the testes develop retroperitoneally in the superior lumbar region on the posterior abdominal
wall (near the kidneys) and must therefore traverse the lateral abdominal muscles.
th th
II. Descend during the 9 to 12 fetal weeks to the deep inguinal canal with the movement caused by the growth of
the vertebral column and pelvis.
III. Testes are guided through the inguinal canal and into the scrotum by the gubernaculum testes which become the
gubernaculum ligaments - cords that extend from the caudal pole of the testes to the scrotum.
IV. Testes are preceded in their descent posterior to the processus vaginalis, a sac of peritoneum.
V. The processus vaginalis covers the anterior and lateral testes with a double layer of peritoneum (both visceral and
parietal peritoneum).
VI. Once the peritoneal sac pinches off from the abdominal peritoneum, the sac becomes known as the tunica
vaginalis.
VII. The testicular arteries are branches of the abdominal aorta and accompany the testes in their descent with nerves,
veins, lymphatics, and the ductus deferens.

Ovarian descent:
I. Embryologically, the ovaries also originate retroperitoneally on the posterior abdominal wall in the superior lumbar
region.
th
II. The ovaries start descent at the 12 fetal week and do not descend past the pelvic cavity.
III. The descent of the ovaries is also guided by the gubernaculum, which attaches from the caudal pole of the ovary to
the labia majora, attaching en route to the uterus.
IV. The gubernaculum becomes:
a. Ovarian ligament - connects the ovary and the uterus
b. Round ligament of the uterus - connects the uterus and the labia majora; this is the portion that passes
through the inguinal canal
V. There is a processus vaginalis formed as part of the peritoneum pinches off during fetal development, but it is
normally obliterated.

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ADrPlexus AGM- SYNAPSE WITH US FOR SUCCESS Anatomy Simplified
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Homologous Structures:
Abdominal Structures: Scrotal Structures:
Skin skin
subcutaneous tissue (superficial superficial (Dartos)
fascia) fascia/muscle
external oblique aponeurosis external spermatic fascia
internal oblique muscle cremaster muscle
fascia for both superficial and deep cremasteric fascia
surfaces of the internal oblique
transversalis fascia internal spermatic fascia
peritoneum tunica vaginalis

Hernias
An abdominal hernia is a protrusion of all or part of an organ or tissue
through an abnormal opening in the abdominal wall.
Groin hernias are inguinal or femoral.
In inguinal hernias, the hernial contents, organs or fatty tissue, protrude
through the inguinal area, which is superior to the inguinal ligament.
In femoral hernias, the hernial contents protrude through the femoral
canal, which is immediately inferior to the inguinal ligament.
Umbilical hernias come through the abdominal wall at or adjacent to the
umbilicus.
Epigastric hernias are uncommon. They protrude through a defect in the
midline fascia between the xiphoid process (lower end of the breastbone)
and the umbilicus.
In incisional hernias, abdominal contents protrude through all of part of a
healed abdominal incision.

Indirect Inguinal hernia Direct Inguinal hernia

Transverses entire inguinal canal Protrudes through relative weakness in
Often enters scrotum posterior wall of inguinal canal
Lateral to inferior epigastric Has hernial sac formed by transversalis
vessels fascia
Hernial sac formed by persistent Does not transverse entire inguinal canal
processus vaginalis and all 3 Protrudes through inguinal triangle that
fascial coverings of spermatic lies between inferior epigastric artery,
cord rectus abdominis and inguinal ligament
(between medial and lateral Leaves medial to inferior epigastric vessels
umbilical folds) (between median and medial folds)

Cryptorchidsm
Cryptorchidism literally means hidden or obscure testis.
It is the most common genital problem encountered in pediatrics
It is synonymous with incomplete testicular descent.
The condition may be unilateral or bilateral.
The term encompasses palpable, nonpalpable, and ectopic
testicles T
he position of testis can be abdominal, inguinal, prescrotal, or
gliding.
Incidence is 3-5% in full term boys, and 1.8% at one year of age.

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Hydrocele
o Hydrocele is an abnormal collection of serous fluid
in the tunica vaginalis covering the testicles or
within some part of processus vaginalis.
o Hydrocele is thee commonest cause of swelling in
the scrotum in the elderly.
o Acquired hydrocle
Primary hydrocele cause not known (common)
Secondary hydrocele secondary to a disease in
testis or epididymis
o Hydrocele fluid contains albumin and fibrinogen. If the contents of a
hydrocele are allowed to drain into a collecting vessel, the liquid does not
clot; however, the fluid coagulates if mixed with even a trace of blood that
has been in contact with damaged tissue.

Varicocele
It is a dilatation of the pampiniform venous plexus and the internal
spermatic vein.
Varicocele is a well-recognized
recognized cause of decreased testicular function and
occurs in approximately 15-20%
20% of all males and in 40% of infertile males.
Obstruction of the left testicular vein by a renal tumour or after
aft
nephrectomy is a cause of varicocele in later life; characteristically, the
varicocele does not decompress in the supine position.

Transpyloric line crosses

fundus of the gallbladder, the neck of the pancreas, the pancreatic body, the origins
of the superior mesenteric artery from the aorta and portal vein, the left and right
colic flexure, the left hilum of the kidney, the right hilum of the kidney, the root of the
transverse mesocolon, duodenojejunal flexure the 2nd part of the duodenum

Referred Pain

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Peritoneum
continuous, glistening, transparent serous membrane that consists of
two layers:
A. Parietal peritoneum: Lining the internal surface of the
abdominopelvic wall
a. Innervated by the intercostal nerves and the
phrenic nerve.
B. Visceral peritoneum: Investing viscera such as spleen
and stomach
a. No sensory supply
C. Peritoneal cavity: potential space between parietal and
visceral peritoneum that has lubricating peritoneal fluid
to allow viscera to move smooth during digestion.
a. There are no organs in the peritoneal cavity.
b. The peritoneal fluid contains WBCs and
antibodies to prevent infection.
c. Completely closed in males but open through
uterine tubes, uterus, and vagina in females.
D. Mesentery: a double layer of peritoneum reflecting away from the abdominal wall to enclose part or all of
one viscera.
a. Constitutes a continuity of visceral and parietal peritoneum that provides a means for
neurovascular communication b/ the organ and the body wall.
b. Has core of connective tissue containing blood vessels, lymphatics, nerves, and fat.
c. Viscera with mesentery are mobile with motility depending on length of mesentery.
E. Peritoneal ligament: consists of a double layer of peritoneum that connects an organ with another organ
or abdominal wall
a. Falciform ligament: connects the liver to the anterior abdominal wall
b. Gastrophrenic ligament: connects the stomach to the inferior surface of the diaphragm
c. Gastrosplenic ligament: connects the spleen to the stomach.
d. Lesser omentum (gastrohepatic and gastroduodenal ligaments): connects the lesser curvature of
the stomach and the proximal part of the duodenum to the liver.
i. Gastrohepatic ligament: continues with and membranous part of the lesser omentum
that connect the stomach to the liver.
ii. Gastroduodenal ligament: continues with and membranous part of the lesser omentum
that connect the duodenum to the liver.
e. Hepatoduodenal ligament: thickened free edge of the lesser omentum that conducts the portal
triad.
f. Greater omentum (gastrocolic ligament): Hangs down form the greater curvature of the stomach
and proximal part of the duodenum, descends, and folds back to attach to the transverse colon
and its mesentery.
F. Omentum: broad, double-layered sheet of
peritoneum passing from the stomach to another
abdominal organ.
a. Greater omentum hangs from the greater
curvature of the stomach and proximal
duodenum down and comes back up to
connect to transverse colon.
b. Lesser omentum connects the lesser
curvature of the stomach and proximal
duodenum to the liver.

Boundaries and surface projections

i. Liver: sharp lower border can be palpated occasionally
ii. Gall bladder: normally not palpable unless enlarged
iii. McBurneys point: 1/3 the distance from Right anterior superior iliac spine to navel (vermiform appendix)
iv. Spleen: parallel to left ribs 9-11. Does not project more forward than mid-axillary line (can only feel it when it is 2-3
times its normal size)

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Blood
Its a liquid connective tissue accounts for 8% of the
human body weight, with an average density of
approximately 1060 kg/m3.
Its formed of plasma & formed elements (cells &
fragments). Once blood is added with anti-coagulant
& centrifuged: It settles in 3 layers.
Formed elements
1. Erythrocytes
2. Thrombocytes
5 kinds of leukocytes
Three kinds of granulocytes
a. neutrophils
b. eosinophils
c. basophils
Two kinds of agranulocytes
a. lymphocytes
b. monocytes
Plasma
Plasma is the straw-colored liquid in which the blood cells are suspended &
makes up 55% of blood volume.
Composition of blood plasma
Component Percent
Water ~92
Proteins 68
Salts 0.8
Lipids 0.6
Glucose (blood sugar) 0.1
Serum Proteins
Proteins make up 68% of the blood. They are about equally divided between
serum albumin and a great variety of serum globulins.
Serum = blood plasma - clotting factors
Electrophoresis
At pH 8.6, which is commonly used, the separated proteins appear as distinct
bands.
The most prominent of these and the one that moves closest to the positive
electrode is serum albumin.
Serum albumin The other proteins are the various serum globulins & they migrate in the order
is made in the liver alpha globulins (e.g., the proteins that transport thyroxine and retinol)
binds many small molecules for beta globulins (e.g., the iron-transporting protein transferrin)
transport through the blood gamma globulins
helps maintain the osmotic Gamma globulins are the least negatively-charged serum proteins.
pressure of the blood Most antibodies are gamma globulins.
Therefore gamma globulins become more abundant following
infections or immunizations.
Bone marrow
Bone marrow consists of hematopoietic cells & supporting stromal cells.
In adults Fat cell:hematopoietic cells ratio is 1:1 means only half of the marrow space is hematopoietically active.
A bone marrow smear typically shows areas where connective tissue adipocytes with large vacuoles predominate.
Increased cell density: e.g., in all strong regeneration or compensation processes, and in cases of leukemia and
myeloproliferative syndromes (except osteomyelosclerosis)
Decreased cell density: e.g., in aplastic processes and myelofibrosis.
o On adults marrow hematopoietic cells consists of :
AGM-Delhi: +91 11 46140148 E-mail us: [email protected]
1 AGM-Mumbai: +91-9870822521 E-mail us: [email protected]
ADR Plexus: +91-9841012335 Web:[email protected]
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60% -Granulocyte precursors 20% -Erytnhrocyte precursors 10% -Lympho,monocyte 10%-undifferentiated ones
precursors precursors
Bone marrow examination
The procedure is most often done on the pelvic bone, but it may also be done on the sternum.
Aspiration Biopsy
Advantages Fast Gives cell and stroma constitution
Gives relative quantity of different cell types Represents all cells
Gives material to further study, e.g. molecular Explains cause of "dry tap" (aspiration
genetics and flow cytometry gives no blood cells)
Drawbacks Doesn't represent all cells Slow processing
o Indications
Evaluate unexplained anemia, leucopenia, thrombocytopenia or pancytopenia
Diagnosis, Diagnosis and staging of lymphoma or solid tumors
monitoring and evaluation of leukemias & multiple myeloma
Evaluate iron level problems
Investigate unexplained splenomegaly
o Ratios of Red Cell Series to White Cell Series -The important ratio of red precursor cells to white cells is 1 : 2 for men and 1 :
3 for women.
Shifts towards erythropoiesis Shifts toward granulopoiesis
seen in all regenerative anemias (hemorrhagic anemia, iron seen in all reactive processes (infections, tumor defence)
deficiency anemia, vitamin deficiency anemia, and hemolysis), and in malignant processes of the white cell series (CML &
pseudopolycythemia (Gaisbck syndrome) and polycythemia. AML)
Haematopoiesis
The dynamic and complex developmental process of the formation of new blood cellular components
All cellular blood components are derived from haematopoietic stem cells
In healthy adult person, about 10*1110*12 new blood cells are produced daily in order to maintain steady state levels in
the peripheral circulation
o Stages: 1-Extramedullary hematopoiesis 2-Medullary hematopoiesis

Extramedullary hematopoiesis
location duration
Primitive yolk sac 3-4 wks up to 8
hematopoiesis wks
Definitive spleen, liver, thymus Up to 20 wks
hematopoiesis and lymph nodes
Medullary hematopoiesis
location duration
Pre natal Bone marrow From 20 wks up
to birth
Post natal marrow of the long Up to 18 yrs
bones
Marrow of flat bones From 18 yrs

Lineages
Multipotent progenitor cells give raise to Common myeloid progenitor (CMP) & Common lymploid progenitor (CLP). These
Common progenitors differentiate to give raise-specific lineages as myeloid & Lymphoid lineages. Such lineages will give raise to
unique committees.
Common myeloid progenitor Myeloid lineage "rubri" committee-RBCs
(CMP) "granulo" committee-eosinophils & basophil
"mono" committee-monocytes
"megakaryo"committee-platelets
Common lymploid progenitor (CLP) Lymphoid lineage "lympho" committee- T-cells, B-cells, NK-cells

AGM-Delhi: +91 11 46140148 E-mail us: [email protected]

2 AGM-Mumbai: +91-9870822521 E-mail us: [email protected]
ADR Plexus: +91-9841012335 Web:[email protected]
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Pluripotency:isis the ability of the human embryonic stem cell

to differentiate or become almost any cell in the body
Multipotent progenitor cells:: have the potential to give rise
to cells from multiple, but a limited number of lineages
Oligopotency:: is the ability of progenitor cells to
differentiate into a few cell types.
unipotent cell: is one that has the capacity to
develop/differentiate into only one type of tissue/cell type.

Hematopoietic stem cell

Its very rare (only about one in 10,000 bone
marrow cells)
Express a cell-surface
surface protein designated CD34;
Produce, by mitosis, two kinds of progeny:
1-More stem cells
Cells that begin to differentiate in to various kind
2-Cells
of blood cells.
Molecular regulation of Haematopoiesis
Interleukin-7 (IL-7) is the major cytokine in stimulating bone marrow stem cells to start down the "lymphoid" path
leading to the various lymphocytes .
Erythropoietin (EPO), produced by the kidneys, enhances the productionproduction of red blood cells (RBCs).
Thrombopoietin (TPO), ), assisted by Interleukin-11
Interleukin (IL-11),
11), stimulates the production of megakaryocytes. Their
fragmentation produces platelets.
Granulocyte-macrophage colony-stimulating
stimulating factor (GM-CSF),
(GM as its name suggests, sendsnds cells down the path leading
to both those cell types. In due course, one path or the other is taken.
Under the influence of granulocyte colony-stimulating
colony factor (G-CSF),
), they differentiate into neutrophils.
Further stimulated by interleukin-5 5 (IL-5)
(IL they develop into eosinophils.
Interleukin-3 (IL-3) participates in the differentiation of most of the white blood cells but plays a particularly prominent
role in the formation of basophils.
Stimulated by macrophage colony-stimulating factor (M-CSF) the granulocyte/macrophage
anulocyte/macrophage progenitor cells
differentiate into monocytes, macrophages, and dendritic cells (DCs).
Red cell indices
Blood Cell count : Blood count shows number of cells Haemoglobin (Hb): 132-135 135 g/l in males & 115-120
115 g/l in
contained in Human Blood. Normally Blood contains 40-50% 40 females. Higher in neonates,, lower in children. Sex difference
(M) & 35-45% (F) cells. Male: 4. 4-5,5, 9 x10 3 /l & Female: 3, negligible until adulthood.
8-5. 2 x10 3 /l Hemoglobin in plasma:1-4 4 mg/dl. Normally diminutive
Red cell life span-120 days compared with inside red blood cells
Hematocrit-The hematocrit (Ht or HCT) or packed cell volume Reticulocytes- 0.5% to 1.5%.
(PCV) or erythrocyte volume fraction (EVF) is the proportion The number of reticulocytes is a good indicator of bone
of blood volume that is occupied by red blood cells.cells It is marrow activity, because it represents recent
normally about 46% for men and 38% for women production. This means that the reticulocyte
reticulocy
count, and the reticulocyte production index
that can be calculated from it, can be used to
determine whether a production problem is
contributing to the anaemia, and can also be used to monitor
the progress of treatment for anaemia.
The Reticulocyte production index (RPI, also called a corrected reticulocyte count) count
The reticulocyte index (RI) should be between 1.0 and 2.0 RI=Ret count*Hct/Normat Hct
for a healthy individual. Hct(%) Ret survival/ maturation
RI < 2 with anemia indicates decreased production of correction
reticulocytes and therefore red blood cells. 36-45 1.0
RI > 2 with anemia indicates loss of red blood cells 26-35 1.5
(destruction, bleeding, etc) leading to increased 16-25 2.0

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compensatory production of reticulocytes to replace the 15-below 2.5

lost red blood cells
Red blood cell distribution width, or RDW,, is a measure of the variation of red blood cell (RBC) width that is reported as part of
a standard complete blood count. Normal reference range in human red blood cells is 11 - 14%.An elevated RDW, i.e. red blood
cells of unequal sizes, is known as anisocytosis.
anisocytosis
v RDW = (Standard deviation of MCV mean MCV) 100
RDW normal RDW increased
anemia of chronic disease iron deficiency
thalassemia dual deficiency (e.g. iron and folate)
myelodysplastic syndrome
AIHA
liver disease
B12/folate deficiency
Mean corpuscular volume (MCV) MCV is the average volume of a red blood cell and is
3
Normal range: 80-100 m MCV=Hct/RBC calculated by dividing the hematocrit (Hct) by the red blood
cell count.
Mean corpuscular hemoglobin (MCH) MCH=Hb/RBC MCH is the average amount of hemoglobin (Hb) per red
Normal range: 27-31 pg/cell blood cell and is calculated by dividing the hemoglobin by
the red blood cell count.
Mean corpuscular hemoglobin concentration MHCH=Hb/Hct MCHC is the average concentration of hemoglobin per red
(MCHC) blood cell and is calculated by dividing the hemoglobin by
Normal range: 32-36 g/dL the hematocrit
APPROACH TO THE BLOOD FILM
Size Colour
macrocytic hypochromasia
increased size Increase in the size of
e.g. low B12, low folate the central pallor
microcytic (normal = less than
reduced size half of the diameter of
e.g. iron deficiency, RBC)
thalassemia polychromasia (blue cells) indicates increased RBC production by the
marrow
Morphology
Normal = discocyte (biconcave)

spherocyte = spherical RBC

e.g. hereditary spherocytosis, immune hemolytic anemia

Fragmented cells (schistocytes) = split RBC, may assume various shapes, some with
horn-like projections (keratocytes), triangle-forms
forms (triangulocytes), and helmet
shapes
e.g. microangiopathic hemolytic anemia (TTP, DIC, vasculitis,
glomerulonephritis), prosthetic heart valve
Elliptocyte (ovalocyte) = oval, elongated RBC
e.g. hereditary elliptocytosis, megaloblastic anemia

Sickle cell = sickle-shaped RBC

e.g. sickle cell disorders, HbSC, HbSS

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Target cell(codocyte) = bell-shaped, Erythrocyte with increased surface area to

volume ratio; appear as target with bullseye in dry slide
e.g. liver disease, hemoglobin S and C, thalassemia, Fe deficiency

Burr cell (Echinocyte )=Spiculated erythrocyte with short, equally-spaced

projections
Uremia , Pyruvate kinase deficiency, Liver disease, Artifact due to improper
drying
Spur cell (Acanthocyte) = Blunted spicules of varying length, irregularly distributed
over cell surface Liver disease
Lipid disorders-abetalipoproteinemia, Hemangiosarcoma, Disseminated
intravascular coagulation
Bite cells = appear when an abnormal hemoglobin aggregate (Heinz body) is nibbled
out of a red cell's cytoplasm by the spleen leaving a bitten apple appearance
Glucose 6-PD deficiency secondary to chemical poisoning or injury by oxidant
drugs are settings for Heinz body formation, and the telltale bite cells remain as
evidence.
Hemolytic anemia associated with severe liver disease is another setting where
bite cells are formed
Knizocyte Stomatocyte Teardrop cell (darcocyte) = single
a red blood cell with two or more The cells appear as "smiling face" or pointed end, looks like a teardrop, e.g.
concavities (triconcave erythrocyte); fish mouth.Seen in hereditary myelofibrosis
associated with hemolytic anemia. stomatocytosis, liver disease or acute
alcoholism

Distribution
Rouleaux formation = aggregates of RBC resembling stacks of coins e.g. artifact, paraprotein
(multiple myeloma, macroglobulinemia)

Inclusion bodies
Nuclei Heinz bodies
o immature RBC o denatured hemoglobin
o indicates serious medical disease o Eg-G6PD deficiency
o Eg-severe anemia, leukemia, bone
marrow metastases
Howell-Jolly bodies Basophilic stippling
o small nuclear remnant with the colour of o deep blue granulations of variable size
a pyknotic nucleus and number, pathologic aggregation of
o Eg-post-splenectomy, hyposplenism, ribosomes
hemolytic anemia, megaloblastic anemia o Eg-Pb intoxication, thalassemia,
sideroblastic anemeia, myelodysplasia & sometimes in
hemolysis
Pappenheimer bodies Parasitic inclusions
o Abnormal granules of Fe, sometimes o Eg-Malaria, Bartonella & Babesiosis
reoffered as siderotic granules
o Eg-sideroblasic anemia & post-
splenectomy

Anaemia
F Anaemia is a decrease in number of RBCs or quantity of Hb in the blood or both.
Classification of anaemia depends
Decreased production vs increased destruction

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Anaemia based on MCV

Physical signs
Head & neck:Pallor of mucous membranes, conjunctivae (Hb < 90 g/L) , icterus, cervical
lymphadenopathy, ocular bruits (Hb < 55 g/L ), glossitis
Skin:pallor, jaundice, skin creases (Hb < 75 g/L ), telangiectasia as in haemolytic anemia,
koilonychia (spoon-shaped nails) as in iron deficiency anemia
CVS: tachycardia, postural changes, systolic flow murmur, wide pulse pressure, CHF
GI: hepatomegaly, splenomegaly, rectal (occult blood)
Iron metabolism
IRON ABSORPTION IRON TRANSPORT
Duodenum: iron combines with apoferritin to form ferritin Majority of non-heme Fe in plasma is bound to transferrin
that is absorbed through villi Transferrin
Plasma transfer of iron from enterocytes to the transport o beta-globulin
protein occurs through specific iron channels, called o carries Fe from mucosal cell to RBC precursors
Ferroportins, and is facilitated by a protein called Hephaestin, in marrow
contains copper, so copper deficiency will decrease iron o carries Fe from storage pool in hepatocytes and
absorption macrophages to RBC precursors in marrow
IRON STORAGE
Fe is stored in two forms: Ferritin and hemosiderin
Ferritin Hemosiderin
Ferric Fe complexed to a protein called apoferritin aggregates or crystals of ferritin with the
hepatocytes are main site of ferritin storage apoferritin partially removed
minute quantities are present in plasma in macrophage-monocyte system is main source of
equilibrium with intracellular ferritin hemosiderin storage
Regulation Fe homeostasis
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron
homeostasis in humans and other mammals.
Hepcidin directly inhibits ferroportin. By inhibiting ferroportin, hepcidin prevents enterocytes of the intestines from secreting
iron into the hepatic portal system, thereby functionally reducing iron absorption.
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Iron release from macrophages is also prevented by ferroportin inhibition. Thus, hepcidin maintains iron homeostasis. Hepcidin
activity is also partially responsible for iron sequestration seen in anemia of chronic disease ( Hepcidin is increased by IL-6)

Factors affecting Fe absorption

Promoters Inhibitor
HCL Achlorhydria & Antacids
Reducing agents-Vit C Oxidents
In Fe2+ form In Fe3+ fom
Inorganic form Organic form
Soluble chelators-AAs, Sugars & alcohol Non-soluble chelators-Phoshphates(milk). Oxalates(Spinach),
Phytates(cereals), Tannin(Tea)

Iron Intake (Dietary) Increased requirement of Fe

average adult diet = 10-20 mg Fe/day infancy-growth spurt ---2x basal need
absorption = 5-10% (0.5-2 mg/day) puberty-growth spurt, menarche---- 3x basal need
males have a positive Fe balance pregnancy-maternal RBC, fetus ---- 4x basal need
menstruating females have a negative Fe blood donation ----- 4x basal need
balance 500 mL blood = 250 mg Fe
4 donations/year = 1 g
Iron indices
F Bone marrow aspirate is the gold standard test for iron stores
Serum ferritin - 30-300 ng/mL for males and 15-200 ng/mL for Total iron binding capacity (TIBC) TIBC- 240-450 g/dL
females (43.0-80.6 mol/L)
single most important blood test for iron stores high specificity for decreased iron, low sensitivity
falsely elevated in inflammatory disease, liver disease (from measure of total amount of transferrin present in blood
necrotic hepatocytes), neoplasm and hyperthyroidism normally, one third of the TIBC is saturated with Fe,
remainder is unsaturated
v serum iron- Transferrin saturation-
Male 65-177 g/dL (11.6- Female 50-170 g/dL Male 20-50% Female 15-50%
31.7 mol/L) (9.0-30.4 mol/L) serum Fe divided by TIBC, expressed as a proportion or a
varies significantly daily %
a measure of all non-heme Fe present in blood The percent transferrin saturation (i.e., the result of the
virtually all serum iron is bound to transferring formula of serum iron/TIBC x 100) can also be a useful
only a trace of serum Fe is free or complexed in ferritin indicator
soluble transferrin receptor (STfR) Index

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a new diagnostic tool

STfR are shortened fragments of the transmembrane transferrin receptor in the circulation
a quantitative determination of the functional iron status and reflects availability of iron at the tissue level low in reduced
erythropoiesis and iron overload, increased in Fe-deficiency anemia, ineffective or increased erythropoiesis
Interpretation of iron indices

Fe deficiency anaemia
o MC cause of
Dietary deficiencies Absorption imbalances
anaemia
(rarely the only etiology) post-gastrectomy
o Imbalance of
cows milk (infant malabsorption/par
intake vs.
diet) asites
requirements or
tea and toast
loss
(elderly)
o May indicate
Hemorrhage Intravascular
the presence of
obvious causes - hemolysis
serious GI
menorrhagia hemoglobinuria
disease
occult - peptic hemosiderinuria
ulcer disease, cardiac valve RBC
aspirin, GI tract fragmentation
cancer
Clinical presentation
iron deficiency may cause fatigue before clinical anemia nails
develops brittle
brittle hair koilonychia
dysphagia (esophageal web, Plummer-Vinson ring) glossitis
angular stomatitis
pica (appetite for bizarre substances e.g. ice, paint, dirt)
Diagnosis
o Major diagnostic difficulty is to distinguish from anemia of chronic disease
serum peripheral blood film
ferritin < 20 is diagnostic of iron deficiency anemia hypochromic microcytosis: RBCs are under hemoglobinized
iron deficiency anemia unlikely if ferritin > 22-322 due to lack of Fe
Low iron level Increased RDW
High total iron-binding capacity (TIBC) pencil forms
Low transferrin percentage saturation target cells (thin)
Increased erythrocyte zinc protoporphyrin levels
platelet count may be elevated(reactive thrombocytosis)
Increased soluble transferrin receptor (sTf-R) levels
Ratio of sTf-R to ferritin is usually >2.5
bone marrow
intermediate and late erythroblasts show micronormoblastic maturation
Fe stain (Prussian blue) shows decreased iron in macrophages
decreased normal sideroblasts
Treatment Recovery time
treat the underlying cause reticulocytes begin to
v different preparations available: tablets, syrup, parenteral (if malabsorption) increase after one week

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v dose: ferrous sulphate 325 mg PO TID or ferrous gluconate 300 mg PO TID until anemia Hb normalizes by 10
corrects and then for 3 months after grams per week
v Iron dextran is the only preparation that can be given IV or IM. Iron dextran can, if serum ferritin is
theoretically, be administered as a single dose to restore the patients iron status to normal normal then discontinue
(total dose infusion) iron therapy
v Sodium ferric gluconate is given intravenously, and up to 80% of the iron is available for
transport by transferrin within 24 hours.
v Iron sucrose is given intravenously.
Refractoriness to treatment
Medication Patient Physician
poor preparation (e.g. expired) poor compliance misdiagnosis
drug interactions continued bleeding
malabsorption (rare)
Anaemia of chronic diseases
o Known chronic disease, particularly inflammatory; symptoms and signs usually those of responsible disease
o Modest anemia (Hct >/= 25%); red cells normal morphologically but may be slightly microcytic
o In anemia of chronic disease, the hemoglobin and hematocrit should not fall below 60% of baseline; if lower, some other
cause of anemia is present.
Etiology Pathophysiology
infections Complex.
cancer Inflammatory cytokines like IL-6 & TNF-
inflammatory and rheumatologic alfa induce hepcidin.
disease They also down regulate Epo-R Tf-R.
renal disease They also produce free radicals to
endocrine disorders (e.g. thyroid) augment hemolysis.
Epo is normal or increased but insufficient
for normal erythropoiesis.
Epo is markedly reduced in CKD.
Hemolytic component
Infiltration of marrow by tumor.

Diagnosis: a diagnosis of exclusion, biochemically rule out Fe deficiency

serum peripheral blood bone marrow
serum iron, TIBC, and % saturation all usually normocytic and normochromic if normal or increased iron
normal or slightly reduced the anemia is mild stores
serum ferritin is normal or increased may be microcytic and normochromic if decreased normal
Normal or decreased soluble transferrin the anemia is moderate sideroblasts
receptor (sTf-R) levels may be microcytic and hypochromic if the
Ratio sTf-R/log ferretin <1 anemia is severe but rarely < 90 g/L)
Treatment
Anemia of chronic disease remains underrecognized and undertreated. Usually resolves if underlying disease is treated.
Transfusion:
Blood transfusions are widely used as a rapid and effective therapeutic intervention. Particularly with severe anemia (in which
the Hb is less than 8.0 g/dL) or life-threatening anemia (in which the Hb is less than 6.5 g /dL) & when the condition is
aggravated by complications such as bleeding.
Latest guidelines for the management of ACD in patients with cancer or chronic kidney disease do not recommend regular blood
transfusion therapy in their management algorithms because of the risks.
Iron therapy:
Controversial. Rcomended in particular, to dialysis patients with a ferritin of <200 ng/mL and a transferring saturation of <25%.
Iron therapy is currently not recommended for patients with anemia of chronic disease who have a high or normal ferritin level.
Erythropoietic agents:
Erythropoietic agents are currently approved for use in the ACD that accompanies chemotherapy, chronic kidney disease, and
infection with human immunodeficiency virus (HIV) undergoing myelosuppressive therapy.
Epoetin-alfa 150 U/kg (SC, 3times/week) Epoetin-alfa 40,000 U/kg (SC/week) Darbepoetin 2.25 g/kg (SC/week
If hemoglobin increases by 1 g/dL in 2-week period, dose should be reduced by 25%. If hemoglobin exceeds 13 g/dL, hold
therapy, reinitiate therapy when hemoglobin decreases to less than 12 g/dL at 25% dose reduction.

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