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Anatomy of AbdomenBoundaries of the abdomen:

1. Superior boundary: the diaphragm2. 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 abdomen3. Posteriorly: the sacrum, pelvic bones, and the sacroiliac joints (near the ala of the sacrum)4. Anteriorly: the pelvic bones articulating at the symphysis pubis5. 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 thigho Lacunar Ligament: runs between inguinal ligament and pectineal line; forms medial part of floor of inguinal canalo Pectineal Ligament: runs along pectineal line of pelvis; separates pelvic and abdominal cavitieso Interfoveolar Ligament: medial thickening of transversalis fascia at deep inguinal ringo Umbilical ligaments: remnants of the umbilical arterieso Median umbilical ligament: remnant of the urachus

Fascia layers:A). Superficial Fascia - divided into two layers:

i. Superficial fatty layer (Camper’s Fascia) – contains adipose tissue and fuses with superficial fascia of thigh; cannot be used to suture

ii. Deep membranous layer (Scarpa’s 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 separatedC). 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.



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 pressureI. 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 anteriorsheath

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 skinsuperficial fascia (Camper’s and Scarpa’s) superficial fascia deep fascia deep fasciaexternal oblique aponeurosis external oblique aponeurosisinternal oblique aponeurosis internal oblique aponeurosisrectus abdominis muscle transversus abdominis aponeurosinternal oblique aponeurosis pyrimidalis muscle in inferiortransversus abdominis aponeurosis rectus abdominis muscletransversalis fascia transversalis fasciaperitoneum peritoneum



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.IV. 10th, 11th posterior intercostals, subcostal arteries: lie superficial to transversus abdominis and deep to rectus

abdominisV. 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 ligamentVII. Femoral artery and great saphenous vein:

a. Superficial circumflex iliacs: runs in superficial fascia along inguinal ligamentb. Superficial epigastrics: runs in superficial fascia toward umbilicus

VIII. Anterior and collateral branches of the posterior intercostal vessels in 10th and 11th spacesIX. Anterior branches of subcostal arteries and veinsX. 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



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 musclesd. 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 canala. Anterior wall

i. External oblique aponeurosis: ii. Internal oblique: reinforces anterior wall of lateral part of canal

b. Posterior walli. Transversalis fascia

ii. Internal oblique & transverse abdominal aponeurosis (join to form conjoint tendon)c. Roof: Internal oblique and transverse abdominis musclesd. Floor: superior surface of inguinal ligament & lacunar ligament

V. Ligaments of inguinal canala. Inguinal ligamentb. Lacunar ligament

VI. Inguinal Ringa. Deep (internal ring): entrance to inguinal canal—outpouching of transversalis fascia; lies superior to

middle of inguinal ligament, lateral to inferior epigastric vesselsb. 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 wallb. Contains spermatic cord or round ligament of uterus and also ilioinguinal nerve (both sexes)

VIII. Surface projections of bony pelvis



a. Iliac crestb. Anterior & Posterior superior iliac spinec. 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.II. Descend during the 9th to 12th 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.II. The ovaries start descent at the 12th 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 uterusb. Round ligament of the uterus - connects the uterus and the labia majora; this is the portion that passes

through the inguinal canalV. There is a processus vaginalis formed as part of the peritoneum pinches off during fetal development, but it is

normally obliterated.



Homologous Structures:Abdominal Structures: Scrotal Structures:

Skin skinsubcutaneous tissue (superficial fascia)

superficial (Dartos) fascia/muscle

external oblique aponeurosis external spermatic fasciainternal oblique muscle cremaster musclefascia for both superficial and deep surfaces of the internal oblique

cremasteric fascia

transversalis fascia internal spermatic fasciaperitoneum 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 Often enters scrotum Lateral to inferior epigastric

vessels Hernial sac formed by persistent

processus vaginalis and all 3 fascial coverings of spermatic cord

(between medial and lateral umbilical folds)

Protrudes through relative weakness in posterior wall of inguinal canal

Has hernial sac formed by transversalis fascia

Does not transverse entire inguinal canal Protrudes through inguinal triangle that

lies between inferior epigastric artery, rectus abdominis and inguinal ligament

Leaves medial to inferior epigastric vessels (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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Hydroceleo 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 the 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 epididymiso Hydrocele fluid contains albumin and fibrinogen. If the contents

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

spermatic vein. Varicocele is a well-recognized cause of decreased testicular function and

occurs in approximately 15-20% of all males and in 40% of infertile males. Obstruction of the left testicular vein by a renal tumour or aft

nephrectomy is a cause of varicocele in later life; characteristically, the varicocele does not decompress in the supine position.

Transpyloric line crossesfundus of the gallbladder, the neck of the pancreas, the pancreatic body, the origins of thecolic 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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Hydrocele is an abnormal collection of serous fluid in the tunica vaginalis covering the testicles or within some part of processus vaginalis.

e commonest cause of swelling in

Primary hydrocele cause not known (common)Secondary hydrocele secondary to a disease in

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.

is a dilatation of the pampiniform venous plexus and the internal

recognized cause of decreased testicular function and 20% of all males and in 40% of infertile males.

Obstruction of the left testicular vein by a renal tumour or after nephrectomy is a cause of varicocele in later life; characteristically, the varicocele does not decompress in the supine position.

Transpyloric line crossesfundus 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

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fundus of the gallbladder, the neck of the pancreas, the pancreatic body, the origins 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



Peritoneum continuous, glistening, transparent serous membrane that consists of

two layers:A. Parietal peritoneum: Lining the internal surface of the

abdominopelvic walla. Innervated by the intercostal nerves and the

phrenic nerve.B. Visceral peritoneum: Investing viscera such as spleen

and stomacha. 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 wallb. Gastrophrenic ligament: connects the stomach to the inferior surface of the diaphragmc. 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 projectionsi. Liver: sharp lower border can be palpated occasionally

ii. Gall bladder: normally not palpable unless enlargediii. McBurney’s 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 It’s a liquid connective tissue accounts for 8% of the human body weight, with an average density of approximately 1060 kg/m3. It’s 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

Ø Three kinds of granulocytes a. neutrophils b. eosinophils c. basophils

Ø 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 6–8 Salts 0.8 Lipids 0.6 Glucose (blood sugar) 0.1

Serum Proteins Proteins make up 6–8% 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 ü is made in the liver ü binds many small molecules for

transport through the blood ü helps maintain the osmotic

pressure of the blood

The other proteins are the various serum globulins & they migrate in the order Ø alpha globulins (e.g., the proteins that transport thyroxine and retinol) Ø beta globulins (e.g., the iron-transporting protein transferrin) Ø gamma globulins

ü Gamma globulins are the least negatively-charged serum proteins. ü Most antibodies are gamma globulins. ü Therefore gamma globulins become more abundant following

infections or immunizations. Bone marrow ü Bone marrow consists of hematopoietic cells & supporting stromal cells. ü In adults Fat cell:hematopoietic cells ratio is 1:1 means only half of the marrow space is hematopoietically active. ü A bone marrow smear typically shows areas where connective tissue adipocytes with large vacuoles predominate. ü Increased cell density: e.g., in all strong regeneration or compensation processes, and in cases of leukemia and

myeloproliferative syndromes (except osteomyelosclerosis) ü Decreased cell density: e.g., in aplastic processes and myelofibrosis. o On adults marrow hematopoietic cells consists of :



60% -Granulocyte precursors 20% -Erytnhrocyte precursors 10% -Lympho,monocyte precursors

10%-undifferentiated ones precursors

Bone marrow examination ü The procedure is most often done on the pelvic bone, but it may also be done on the sternum.

Aspiration Biopsy Advantages ü Fast

ü Gives relative quantity of different cell types ü Gives material to further study, e.g. molecular

genetics and flow cytometry

ü Gives cell and stroma constitution ü Represents all cells ü Explains cause of "dry tap" (aspiration

gives no blood cells) Drawbacks Doesn't represent all cells Slow processing o Indications

ü Evaluate unexplained anemia, leucopenia, thrombocytopenia or pancytopenia ü Diagnosis, Diagnosis and staging of lymphoma or solid tumors ü monitoring and evaluation of leukemias & multiple myeloma ü Evaluate iron level problems ü 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 deficiency anemia, vitamin deficiency anemia, and hemolysis), pseudopolycythemia (Gaisböck syndrome) and polycythemia.

seen in all reactive processes (infections, tumor defence) and in malignant processes of the white cell series (CML & AML)

Haematopoiesis ü The dynamic and complex developmental process of the formation of new blood cellular components ü All cellular blood components are derived from haematopoietic stem cells ü In healthy adult person, about 10*11–10*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

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 (CMP)

Myeloid lineage "rubri" committee-RBCs "granulo" committee-eosinophils & basophil "mono" committee-monocytes "megakaryo"committee-platelets

Common lymploid progenitor (CLP) Lymphoid lineage "lympho" committee- T-cells, B-cells, NK-cells

Extramedullary hematopoiesis location duration Primitive hematopoiesis

yolk sac 3-4 wks up to 8 wks

Definitive hematopoiesis

spleen, liver, thymus and lymph nodes

Up to 20 wks

Medullary hematopoiesis location duration Pre natal Bone marrow From 20 wks up

to birth Post natal marrow of the long

bones Up to 18 yrs

Marrow of flat bones From 18 yrs

http://en.wikipedia.org/wiki/Molecular_genetics

http://en.wikipedia.org/wiki/Molecular_genetics

http://en.wikipedia.org/wiki/Flow_cytometry

http://en.wikipedia.org/wiki/Flow_cytometry

http://en.wikipedia.org/wiki/Bone_marrow_stroma

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Molecular regulation of Haematopoiesis ü 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 .ü Erythropoietin (EPO), produced by the kidneys, enhances the productiü Thrombopoietin (TPO), assisted by Interleukin

fragmentation produces platelets. ü Granulocyte-macrophage colony-stimulating factor (GM

to both those cell types. In due course, one path or the other is taken.ü Under the influence of granulocyte colonyü Further stimulated by interleukin-5 (ILü 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. ü Stimulated by macrophage colony-

differentiate into monocytes, macrophages, and dendritic cells (DCs).Red cell indices

Blood Cell count : Blood count shows number of cells contained in Human Blood. Normally Blood contains 40(M) & 35-45% (F) cells. Male: 4. 4-5, 9 x10 3 /µl & Female: 3, 8-5. 2 x10 3 /µl Red cell life span-120 days Hematocrit-The hematocrit (Ht or HCT) or packed cell volume(PCV) or erythrocyte volume fraction (EVF) is the proportion of blood volume that is occupied by red blood cellsnormally about 46% for men and 38% for women

The Reticulocyte production indexü The reticulocyte index (RI) should be between 1.0 and 2.0

for a healthy individual. ü RI < 2 with anemia indicates decreased production of

reticulocytes and therefore red blood cells.ü RI > 2 with anemia indicates loss of red blood cells

(destruction, bleeding, etc) leading to increased

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Pluripotency:is the ability of the human embryonic stem cell to differentiate or become almost any cell in the bodyMultipotent progenitor cells: have the potential to give rise to cells from multiple, but a limited number of 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

ü It’s very rare (only about one in 10,000 bone marrow cells)

ü Express a cell-surface protein designated CD34;ü Produce, by mitosis, two kinds of progeny:

1-More stem cells 2-Cells that begin to differentiate in to various kind of blood cells.

is the major cytokine in stimulating bone marrow stem cells to start down the "lymphoid" path leading to the various lymphocytes .

produced by the kidneys, enhances the production of red blood cells (RBCs).), assisted by Interleukin-11 (IL-11), stimulates the production of megakaryocytes. Their

stimulating factor (GM-CSF), as its name suggests, sends cells down the path leading to both those cell types. In due course, one path or the other is taken.

granulocyte colony-stimulating factor (G-CSF), they differentiate into neutrophils.5 (IL-5) they develop into eosinophils.

participates in the differentiation of most of the white blood cells but plays a particularly prominent

stimulating factor (M-CSF) the granulocyte/macrophage progenitor cells differentiate into monocytes, macrophages, and dendritic cells (DCs).

Blood count shows number of cells contained in Human Blood. Normally Blood contains 40-50%

5, 9 x10 3 /µl & Female: 3,

Haemoglobin (Hb): 132-135 g/l in males & 115females. Higher in neonates, lower in children. Sex difference negligible until adulthood. Hemoglobin in plasma:1-4 mg/dl. Normally diminutive compared with inside red blood cells

packed cell volume (EVF) is the proportion

red blood cells. It is normally about 46% for men and 38% for women

Reticulocytes- 0.5% to 1.5%. The number of reticulocytes is a good indicator of marrow activity, because it represents recent production. This means that the reticulocycount, 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.

production index (RPI, also called a corrected reticulocyte countThe reticulocyte index (RI) should be between 1.0 and 2.0

RI < 2 with anemia indicates decreased production of reticulocytes and therefore red blood cells.

2 with anemia indicates loss of red blood cells (destruction, bleeding, etc) leading to increased

RI=Ret count*Hct/Normat HctHct(%) Ret survival/ maturation

36-45 26-35 16-25

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is the ability of the human embryonic stem cell to differentiate or become almost any cell in the body

: have the potential to give rise to cells from multiple, but a limited number of lineages

: is the ability of progenitor cells to differentiate into a few cell types.

is one that has the capacity to develop/differentiate into only one type of tissue/cell type.

about one in 10,000 bone

surface protein designated CD34; Produce, by mitosis, two kinds of progeny:

Cells that begin to differentiate in to various kind

is the major cytokine in stimulating bone marrow stem cells to start down the "lymphoid" path

on of red blood cells (RBCs). 11), stimulates the production of megakaryocytes. Their

nds cells down the path leading

), they differentiate into neutrophils.

participates in the differentiation of most of the white blood cells but plays a particularly prominent

anulocyte/macrophage progenitor cells

135 g/l in males & 115-120 g/l in , lower in children. Sex difference

4 mg/dl. Normally diminutive compared with inside red blood cells

The number of reticulocytes is a good indicator of bone activity, because it represents recent

production. This means that the reticulocyte 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.

corrected reticulocyte count) RI=Ret count*Hct/Normat Hct

Ret survival/ maturation correction

1.0 1.5 2.0

http://en.wikipedia.org/wiki/Haemoglobin

http://en.wikipedia.org/wiki/Neonate

http://en.wikipedia.org/wiki/Hemoglobin

http://en.wikipedia.org/wiki/Blood

http://en.wikipedia.org/wiki/Red_blood_cell

http://en.wikipedia.org/wiki/Bone_marrow

http://en.wikipedia.org/wiki/Bone_marrow

HAEMATOLOGY BUSTER

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compensatory production of reticulocytes to replace the 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 rangecells of unequal sizes, is known as anisocytosis

v RDW = (Standard deviation of MCVRDW normal

ü anemia of chronic disease ü thalassemia

Mean corpuscular volume (MCV) Normal range: 80-100 μm3

Mean corpuscular hemoglobin (MCH) Normal range: 27-31 pg/cell

Mean corpuscular hemoglobin concentration (MCHC) Normal range: 32-36 g/dL

Size Ø macrocytic increased size e.g. low B12, low folate

Ø microcytic reduced size e.g. iron deficiency, thalassemia

Morphology

Normal = discocyte (biconcave)

spherocyte = spherical RBC ü e.g. hereditary spherocytosis, immune hemolytic anemia

Fragmented cells (schistocytes) = split RBC, may assume various shapes, some with horn-like projections (keratocytes), triangle-forms (triangulocytes), and helmet shapes ü e.g. microangiopathic hemolytic anemia (TTP, DIC, vasculitis,

glomerulonephritis), prosthetic heart valve

Elliptocyte (ovalocyte) = oval, elongated RBCü e.g. hereditary elliptocytosis, megaloblastic anemia

Sickle cell = sickle-shaped RBC ü e.g. sickle cell disorders, HbSC, HbSS

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compensatory production of reticulocytes to replace the 15-below

, is a measure of the variation of red blood cell (RBC) width that is reported as part of reference range in human red blood cells is 11 - 14%.An elevated RDW, i.e. red blood

anisocytosis. MCV ÷ mean MCV) × 100

RDW increased ü iron deficiency ü dual deficiency (e.g. iron and folate)ü myelodysplastic syndromeü AIHA ü liver disease ü B12/folate deficiency

MCV=Hct/RBC

MCV is the average volume of a red blood cell and is calculated by dividing the hematocritcell count.

MCH=Hb/RBC MCH is the average amount of 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 blood cell and is calculated by dividing the hemoglobin by the hematocrit

APPROACH TO THE BLOOD FILM

Colour Ø hypochromasia Increase in the size of the central pallor (normal = less than half of the diameter of RBC) Ø polychromasia (blue cells) indicates increased RBC production by the

marrow

e.g. hereditary spherocytosis, immune hemolytic anemia

= split RBC, may assume various shapes, some with forms (triangulocytes), and helmet

e.g. microangiopathic hemolytic anemia (TTP, DIC, vasculitis, glomerulonephritis), prosthetic heart valve

= oval, elongated RBC e.g. hereditary elliptocytosis, megaloblastic anemia

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2.5

, is a measure of the variation of red blood cell (RBC) width that is reported as part of 14%.An elevated RDW, i.e. red blood

dual deficiency (e.g. iron and folate) myelodysplastic syndrome

MCV is the average volume of a red blood cell and is hematocrit (Hct) by the red blood

MCH is the average amount of hemoglobin (Hb) per red blood cell and is calculated by dividing the hemoglobin by

MCHC is the average concentration of hemoglobin per red calculated by dividing the hemoglobin by

(blue cells) indicates increased RBC production by the

http://en.wikipedia.org/wiki/Reference_range

http://en.wikipedia.org/wiki/Anisocytosis

http://en.wikipedia.org/wiki/Standard_deviation

http://en.wikipedia.org/wiki/Mean_corpuscular_volume

http://en.wikipedia.org/wiki/Arithmetic_mean

http://en.wikipedia.org/wiki/Hematocrit

http://en.wikipedia.org/wiki/Hemoglobin



Target cell(codocyte) = bell-shaped, Erythrocyte with increased surface area to volume ratio; appear as target with bullseye in dry slide ü e.g. liver disease, hemoglobin S and C, thalassemia, Fe deficiency

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

ü Hemolytic anemia associated with severe liver disease is another setting where bite cells are formed

Knizocyte a red blood cell with two or more concavities (triconcave erythrocyte); associated with hemolytic anemia.

Stomatocyte The cells appear as "smiling face" or fish mouth.Seen in hereditary stomatocytosis, liver disease or acute alcoholism

Teardrop cell (darcocyte) = single pointed end, looks like a teardrop, e.g. myelofibrosis

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

Inclusion bodies

Nuclei o immature RBC o indicates serious medical disease o Eg-severe anemia, leukemia, bone

marrow metastases

Heinz bodies o denatured hemoglobin o Eg-G6PD deficiency

Howell-Jolly bodies o small nuclear remnant with the colour of

a pyknotic nucleus o Eg-post-splenectomy, hyposplenism,

hemolytic anemia, megaloblastic anemia

Basophilic stippling o deep blue granulations of variable size

and number, pathologic aggregation of ribosomes

o Eg-Pb intoxication, thalassemia, sideroblastic anemeia, myelodysplasia & sometimes in hemolysis

Pappenheimer bodies o Abnormal granules of Fe, sometimes

reoffered as siderotic granules o Eg-sideroblasic anemia & post-

splenectomy

Parasitic inclusions o Eg-Malaria, Bartonella & Babesiosis

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



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 that is absorbed through villi Plasma transfer of iron from enterocytes to the transport protein occurs through specific iron channels, called Ferroportins, and is facilitated by a protein called Hephaestin, contains copper, so copper deficiency will decrease iron absorption

Majority of non-heme Fe in plasma is bound to transferrin Transferrin

o beta-globulin o carries Fe from mucosal cell to RBC precursors

in marrow o carries Fe from storage pool in hepatocytes and

macrophages to RBC precursors in marrow IRON STORAGE Fe is stored in two forms: Ferritin and hemosiderin

Ferritin • Ferric Fe complexed to a protein called apoferritin • hepatocytes are main site of ferritin storage • minute quantities are present in plasma in equilibrium with intracellular ferritin

Hemosiderin • aggregates or crystals of ferritin with the apoferritin partially removed • macrophage-monocyte system is main source of 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.

http://en.wikipedia.org/wiki/Peptide_hormone

http://en.wikipedia.org/wiki/Liver

http://en.wikipedia.org/wiki/Human_iron_metabolism

http://en.wikipedia.org/wiki/Human_iron_metabolism

http://en.wikipedia.org/wiki/Mammal

http://en.wikipedia.org/wiki/Ferroportin

http://en.wikipedia.org/wiki/Enterocytes

http://en.wikipedia.org/wiki/Hepatic_portal_system



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 absorption = 5-10% (0.5-2 mg/day)

• males have a positive Fe balance

• menstruating females have a negative Fe balance

infancy-growth spurt ---2x basal need puberty-growth spurt, menarche---- 3x basal need pregnancy-maternal RBC, fetus ---- 4x basal need blood donation ----- 4x basal need

• 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 females ü single most important blood test for iron stores ü falsely elevated in inflammatory disease, liver disease (from

necrotic hepatocytes), neoplasm and hyperthyroidism

Total iron binding capacity (TIBC) TIBC- 240-450 μg/dL (43.0-80.6 μmol/L) ü high specificity for decreased iron, low sensitivity ü measure of total amount of transferrin present in blood ü normally, one third of the TIBC is saturated with Fe,

remainder is unsaturated

v serum iron-

Male 65-177 μg/dL (11.6-31.7 μmol/L)

Female 50-170 μg/dL (9.0-30.4 μmol/L)

ü varies significantly daily ü a measure of all non-heme Fe present in blood ü virtually all serum iron is bound to transferring ü only a trace of serum Fe is free or complexed in ferritin

Transferrin saturation- Male 20-50% Female 15-50%

ü serum Fe divided by TIBC, expressed as a proportion or a %

ü The percent transferrin saturation (i.e., the result of the formula of serum iron/TIBC x 100) can also be a useful indicator

soluble transferrin receptor (STfR) Index

http://en.wikipedia.org/wiki/Macrophages

http://en.wikipedia.org/wiki/Ferroportin

http://en.wikipedia.org/wiki/Iron_homeostasis

http://en.wikipedia.org/wiki/Anemia_of_chronic_disease

http://en.wikipedia.org/wiki/Transferrin_saturation



ü a new diagnostic tool ü STfR are shortened fragments of the transmembrane transferrin receptor in the circulation ü 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 anaemia

o Imbalance of intake vs. requirements or loss

o May indicate the presence of serious GI disease

Clinical presentation

ü iron deficiency may cause fatigue before clinical anemia develops

ü brittle hair ü dysphagia (esophageal web, Plummer-Vinson ring)

ü nails • brittle • koilonychia

ü glossitis ü angular stomatitis ü pica (appetite for bizarre substances e.g. ice, paint, dirt)

Diagnosis o Major diagnostic difficulty is to distinguish from anemia of chronic disease

serum ü ferritin < 20 is diagnostic of iron deficiency anemia ü iron deficiency anemia unlikely if ferritin > 22-322 ü Low iron level ü High total iron-binding capacity (TIBC) ü Low transferrin percentage saturation ü Increased erythrocyte zinc protoporphyrin levels ü platelet count may be elevated(reactive thrombocytosis) ü Increased soluble transferrin receptor (sTf-R) levels ü Ratio of sTf-R to ferritin is usually >2.5

peripheral blood film • hypochromic microcytosis: RBCs are under hemoglobinized due to lack of Fe

• Increased RDW • pencil forms • target cells (thin)

bone marrow • intermediate and late erythroblasts show micronormoblastic maturation • Fe stain (Prussian blue) shows decreased iron in macrophages • decreased normal sideroblasts

Treatment treat the underlying cause v different preparations available: tablets, syrup, parenteral (if malabsorption)

Recovery time ü reticulocytes begin to

increase after one week

Dietary deficiencies (rarely the only etiology)

ü cow’s milk (infant diet)

ü ”tea and toast” (elderly)

Absorption imbalances ü post-gastrectomy ü malabsorption/par

asites

Hemorrhage ü obvious causes -

menorrhagia ü occult - peptic

ulcer disease, aspirin, GI tract cancer

Intravascular hemolysis ü hemoglobinuria ü hemosiderinuria ü cardiac valve RBC

fragmentation



v dose: ferrous sulphate 325 mg PO TID or ferrous gluconate 300 mg PO TID until anemia corrects and then for 3 months after

v Iron dextran is the only preparation that can be given IV or IM. Iron dextran can, theoretically, be administered as a single dose to restore the patient’s iron status to normal (total dose infusion)

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.

ü Hb normalizes by 10 grams per week

ü if serum ferritin is normal then discontinue iron therapy

Refractoriness to treatment

Medication • poor preparation (e.g. expired) • drug interactions

Patient • poor compliance • continued bleeding • malabsorption (rare)

Physician • misdiagnosis

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 ü infections ü cancer ü inflammatory and rheumatologic

disease ü renal disease ü endocrine disorders (e.g. thyroid)

Pathophysiology • Complex. • Inflammatory cytokines like IL-6 & TNF-

alfa induce hepcidin. • They also down regulate Epo-R Tf-R. • They also produce free radicals to

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 ü serum iron, TIBC, and % saturation all

normal or slightly reduced ü serum ferritin is normal or increased ü Normal or decreased soluble transferrin

receptor (sTf-R) levels ü Ratio sTf-R/log ferretin <1

peripheral blood ü usually normocytic and normochromic if

the anemia is mild ü may be microcytic and normochromic if

the anemia is moderate ü may be microcytic and hypochromic if the

anemia is severe but rarely < 90 g/L)

bone marrow • normal or increased iron stores • decreased “normal” sideroblasts

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 μg/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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